Nutritional Deficiencies: Mineral, Vitamin and Fatty Acid



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Vitamin & Mineral Deficiencies & Supplementation - General
Fillers in capsules and tablets - Stearic Acid and Magnesium Stearate
Mineral Deficiencies
     General
     Sodium
     Magnesium
     Potassium
     Calcium
     Zinc
     Iron
Vitamin Deficiencies
     Vitamin Definition List
     Vitamins A, C & E
     Vitamin D and UV Light Exposure
     B vitamins and Supplementation - General
     Thiamin (B1) and TDP/TPP
     Riboflavin (B2), FMN and FAD
     Niacin (B3) and NAD
     Pantothenic Acid (B5)
     Vitamin B6 and P-5-P
     Biotin (B7)
     Inositol (B8) and IP6
     Folic Acid (B9), Folate and 5-MTHF
     Vitamin B12
     Naturally sourced supplemental forms of B-vitamins
     B-Vitamin Dosages for CFS Sufferers
Assimilable Protein Sources: Spirulina, Chlorella and Quality Whey
     General
     Quality Whey
     Spirulina
     Chlorella
     Spirulina vs Chlorella
     Other Green 'Superfoods'
     Other Protein Sources
Protein Function & Amino Acid Conversion
     General
     Amino Acid Categories
     Protein and Protein Structures
     Amino Acid Conversion and Protein Formation Bottlenecks
     Taurine
     Cysteine and Cystine
     Glutamic Acid
     Asparagine
     Beta-Alanine
     Sarcosine
     Amino Acid Supplementation - General Principles
Homocysteine Metabolism, Methylation, Transsulphuration & Glutathione Production
     What is Methylation?
     What role do Methionine and Homocysteine play in Transsulphuration and Glutathione production?
     Conversion of Methionine into Homocysteine
     The Function of S-AdenosylMethionine (SAM-e)
     Conversion of Homocysteine into Cysteine
     The function of Cysteine
     Re-Conversion of Homosysteine back into Methionine
     The requirements for Folate, P5P and Methyl B12
     B-Vitamin Deficiencies and the results of high Homocysteine / low Glutathione levels
     Betaine as a homocysteine regulator and methylator
Antioxidants
Fatty Acid Imbalances
     Omega 3
     Omega 6
     Omega 7
     Omega 9
     Saturated Fats
     Trans Fats
     The Importance of correct Omega 6 to Omega 3 Ratio
     Cholesterol
     Maintaining a good oil balance
Phospholipid Deficiencies

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Last Updated: 23 Jan 2016


Vitamin & Mineral Deficiencies & Supplementation - General:

From the
digestive disorders section, it is clear that an impaired digestive system will fail to break down and assimilate all the vitamins, minerals and amino acids that the body requires to function perfectly. Stress can be a major factor in digestive efficiency in that blood circulation is reduced in the intestinal capillaries during periods of stress, resulting in reduced absorption of nutrients from food in the stomach and intestines. Stress is also a major contributary factor in making poor food choices (e.g. comfort foods). In addition, excessive partial detoxification products and other congestion on the cellular and mitochondrial membranes inhibit proper assimilation and carriage of nutrients into the cells (please see the toxification page). Over time, these factors can cause extreme nutrient deficiencies within the body, which have severely impact numeous bio-chemical processes and our well being. Not only this, but our diets are frequently low in certain elements too, such as Magnesium, exaccerbating the problem even further. Please note that anyone who engages in regular activities involving sweating (!), whether they are saunas, work outs etc., it is very important to replace the lost electrolyte minerals calcium, magnesium, sodium, potassium and chloride either in one's diet or through supplementation (or both) as otherwise this can result in severe mineral depletion over time and mineral deficiencies. An active lifestyle involving regular saunas, sweating in hot climates, or regular jogging or work outs combined with poor diet, nutritional input and toxification can result in severe mineral and vitamin deficiencies and chronic fatigue.

For such people, taking a multi-vitamin and mineral supplement is neither here nor there. But it is of some value. The simplest way to ascertain mineral deficiencies is to have a hair mineral analysis performed. This is of course not the most reliable method of measuring nutritional and toxic mineral levels but it is a quick and dirty indicator, does not require a doctor necessarily and is a useful introductory test before moving onto more sophisticated tests. Certain vitamins will be identified by such a hair analysis also, but for B-Vitamins, more sophisticated tests are required, such as urine or blood tests. You need to ascertain what you are chronically deficient of, and then engage in a regime of supplementation for that deficiency over a period of months to provide the body with what it needs to function properly. In addition, an energetic therapy will also assist in promoting proper digestive function, to address the root cause of the problem (assuming the actual diet is healthy and varied and sufficient in the requisite nutrients and food types). Such therapies are outlined on the energetic therapies page. A supplementation programme and complimentary therapy programme should be co-ordinated in conjunction with a doctor or consultant.

In addition, nutrients are likely better absorbed from the digestive system into the blood and from the blood into the cell membranes of the tissues if the nutrients, water content of the blood and indeed the cells themselves are highly electromagnetically charged. It is likely that the use of an FIR sauna just at the moment (or perhaps just before) of taking the vitamin or mineral supplements may aid absorption. The wearing of devices to stimulate the electromagnetic field of the body may well have such an effect also. Please see the electromagnetic deficiencies page and toxicity page for more information.

Vitamin supplements, and indeed any other liquid supplement or detoxification product can be taken sublingually rather than simply swallowed. Sublingual absorption literally means under the tongue, through the capillaries under the tongue and directly into the blood stream, rather than having to pass through the digestive tract and be absorbed through the digestive wall enzymatically. This method of sublingual absorption is more effective and direct, and indeed quicker. Some vitamins and formulations come in a sublingual liquid form, but others can simply be chewed with saliva and the mixture then pushed and held under the tongue for 30 seconds before being swallowed for maximum absorption. However, there is the issue of the rate of absorption to consider, with some supplements being dosed for absorption in the GI tract, which in some cases may be very inefficient, and chewing or sucking these supplements may thus result in extremely high dosages being absorbed directly into the blood stream; there is also the issue of concentration, with oral supplements often being taken with water, diluting their concentration, with sublingual being absorbed with a relatively high concentration. The above applies mostly to mineral supplements, especially to trace elements. There is also the issue of tooth decay, and if you take sublingual supplements regularly throughout the day, which in most cases should not be necessary, then you may suffer form excessive tartar build up.

Capsules are probably easier to absorb than tablets when it comes to supplements. Capsules contain a powder, sometimes compressed, but it is still in powder form, and once the gelatin or cellulose capsule gets waterlogged and dissolves, the contents can easily dissolve into the stomach juices/liquid; whereas tablets are highly compressed and tend to dissolve much more slowly, sometimes not at all and can be seen in the stool if not drunk with enough water.

It could be argued that nutritional supplements are a waste of time, on account of the fact that the vast majority are articifically synthesised or derived from petroleum products or coal-tar, and on a molecular level do not have the same structure/spin as their naturally occurring counterparts, and are thus second best or even worthless or harmful. This is not my personal opinion, at least regarding minerals, as they are by definition single molecules (their electromagnetic properties being another matter). There is probably some truth to this regarding vitamins, especially B-vitamins, and natural sources (either in the form of food or plant/fish extracts/concentrates) may well be more effective than their synthetic counterparts when taken in MUCH higher dosages. It is clearly better to obtain all of one's nutritional needs from a healthy diet, but in the case of chronic deficiencies and digestive impairment (i.e. the inability to break down, extract and absorb nutrients from food into the body's cells), and in the view of soil depletion and the likely inferior nutritional qualities of non-organic food sources, a combination of a healthy diet (including those food types that are high in the nutritional elements, vitamins and oils that the body is deficient in), plant/fish extracts/concentrates and temporary supplementation (as required) is highly likely to be best. In general, it is much better to endeavour to obtain one's antioxidant needs from nutritional sources. The same can be said for vitamins and minerals. Probably an optimal approach is to assume one is only to get one's nutrient intake from food alone, and alter one's diet to get enough antioxidants and whichever minerals one is particularly deficient in, and then supplement on top of that. Supplementation is an easy way to become lazy and eat only a mediocre diet, becoming reliant on the supplements, which are in some respects an inferior form of nutrition. Of course, some 'supplements' are actually dried forms of natural products, which can be good nutritional or food sources to eat in conjunction with one's regular diet, which will have a broad spectrum of nutrients, as opposed to taking a specific chemically prepared supplement compound.

Supplements vary in quality, dosages, price and in terms of (combinations of) ingredients. Some may contain more solvent residues than others; some may have a higher level of stability; and some may have low yeast, fungus or mould counts. Some include the main active ingredient in a superior chemical form than others. It is best to seek advice over what would suit you best or to test them using muscle testing, for example.

There is certainly no point in introducing too many new supplements in one go, as one cannot tell which supplement contributed to any immediate progress one experienced. Or indeed if one felt worse, what has contributed to it. Sometimes it is easy to forget the cumulative effect of various supplements, especially regarding detoxification; or those that contain the same ingredient (e.g. Magnesium etc.) Always read the labels and think about what you are taking.

If you find yourself taking a larger and larger number of supplements, then you may wish to re-evaluate your position, and whether you still need to be taking some of them. It is clearly cheaper, and more economical and efficient, to take less but those that are going to have the greatest impact. Think one or two heat seeking missiles rather than a sky full of anti-aircraft fire to 'neutralise' your target. More is not necessarily better, in terms of numbers of supplements and dosages of each supplement, and overdoing it may simply confuse the body (creating too much 'noise') and 'train' the body to ignore most of what you put into it, and even perhaps encouraging it to utilise inferior chemicals from your supplements in preference to those from your actual diet. In addition there may be unwanted side effects from taking too much of any one type of supplement, including mineral or amino acid imbalance, toxicity/liver/kidney overload or even excessive acidity/alkalinity. One may wish to also try cutting back on one's supplements occasionally to virtually zero, just taking the minimum to get by, e.g. a minimal amount of digestive enzymes and betaine HCl with meals, and perhaps something at night to assist with sleeping e.g. 5HTP or Melatonin. Do this for a few days and feel the difference. If you had been taking too many supplements previously, you may feel like you can 'breathe' again.

Some additional reasons for not taking too many supplements are listed further below (e.g. too much magnesium stearate intake - a waxy, rubbery substance). You may wish to evaluate or discuss this with your practitioner, and perhaps consider eliminating some supplements and seeing what difference it makes.

Those who live outside of the USA, particularly in Australia or in the UK, may find that supplement prices are very high in relative terms, and may want to consider ordering supplements directly from the USA, where they can be 2-3 cheaper, which when bought in bulk orders or together, more than compensates for the shipping and VAT costs. This can save a large amount of money if supplements are purchased regularly. Please see the Links page for more information.

Bear in mind that taking supplements is not an excuse to breach your now slightly higher limits than you would have without them. The whole purpose of it is to assist you in your recovery. You need to allow yourself the space to recover. If you get too excited and want to go back to being 'normal' and catch up on all your tasks, then you will not be achieving anything, or worse. One can view supplements and nutritional support as an 'artificial level of health' or an illusion, whereby one should still tread cautiously as it is not as firm a footing as it seems sometimes and the ground can easily sink beneath you. Try to be mindful of the whole purpose of what you are doing and work with it, not against it.

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Fillers in capsules and tablets - Stearic Acid and Magnesium Stearate:

There are two things one should consider when it comes to tablet or capsule based supplements.

- Capsules require, well, a capsule! This can either be made from microcrystalline cellulose (vegetable sourced, aka vegecaps) or gelatin (animal bone sourced). Gelatin is also high in free-glutamate and for this reason should be avoided if possible. However, gelatin capsules are relatively uncommon on account of the increasingly large market share of vegetarians and vegans.

- Both capsules and tablets tend to use a filler, magnesium stearate and/or stearic acid. Stearic acid is a saturated fatty acid, a waxy solid contain 18 carbon molecules. Magnesium stearate is the magnesium salt of stearic acid. It is used in candles, soap (forming soap scum in water) and supplements etc. Magnesium stearate is a white substance, insoluble in water, and melting at 88C. It has lubricating properties and stops ingredients sticking to manufacturing equipment during compression when tablets are pressed out of raw materials.

http://en.wikipedia.org/wiki/Stearic_acid

http://en.wikipedia.org/wiki/Magnesium_stearate

Stearic acid occurs naturally in animal and vegetable fats and oils. The usual source is bovine, unless otherwise stated. For example, 7% of the total fat contact of Flaxseed oil is stearic acid. It also constitutes 7.7% of the total fat content of breast milk.

However, to be precise, stearic acid is one of several possible fatty acids that make up a triglyceride. It is actually the triglycerides that occur naturally in the foods described above that contain stearic acid. One would not actually find stearic acid in any of these food sources on its own.

A triglyceride is a glycerol that has been esterified with three fatty acids. Triglycerides are the main fat component of many animal and vegetable fats/oils. High levels of triglycerides in the blood stream have been linked to heart disease. Most animal and vegetable oils and fats contain a variety of different types of fats (polyunsaturated, monounsaturated and saturated fatty acids) as well as some triglycerides. Most triglycerides do not contain stearic acid. Cocoa however contains very few different triglycerides, and is particuarly rich in the triglyceride containing palmitic, oleic and stearic acid, in that order.

http://en.wikipedia.org/wiki/Triglycerides

To isolate stearic acid or break it off the larger triglyceride molecules in which it is found, it is necessary to hydrogenate the animal and vegetable fats/oils in order to produce glycerol and the three separate fatty acids. It is not possible to produce it any other way. The stearic acid can then be separated from this fraction. Often what is called stearic acid is in fact a mixture of palmitic and stearic acid.

www-personal.une.edu.au/~sglover/CHEM303%20Chapter%201%20HTML/sld006.htm

According to Wikipedia:

http://en.wikipedia.org/wiki/Stearic_acid

'Stearic acid is prepared by treating animal fat with water at a high pressure and temperature, leading to the hydrolysis of triglycerides. It can also be obtained from the hydrogenation of some unsaturated vegetable oils. Common stearic acid is actually a mix of stearic acid and palmitic acid, although purified stearic acid is available separately.'

Of course, hydrogenation of vegetable oils is the method used to produced partially or fully hydrogenated vegetable oils, a.k.a. trans fats. These are types of unsaturated fats with trans-isomer fatty acid(s). Trans fats may be monounsaturated or polyunsaturated. Trans fats are discussed in the section below on Fatty Acids. However, breaking down triglycerides produces three saturated fatty acids. These are not trans fats, despite the negative association with hydrogenation.

Dr Ron claims that vegetarian stearate is made by the hydrogenation of cottonseed or palm oil, but makes the incorrect assumption that the product of triglyceride hydrogenation is a trans fat. There may well be trans fats produced during the hydrogenation process but these are not used and are separate comopunds to stearic acid. This error aside, Dr Ron also points out that cottonseed oil also has the highest content of pesticide residues of all commercial oils apparently; and that it is possible that the metal catalyst used in the hydrogenation process may contaminate the stearates produced.

www.drrons.com/beware-of-additives-in-supplements.htm

Studies have also shown that stearate coated ingredients take longer to dissolve in water and thus take longer to be absorbed by the body, because stearates are waxy and insoluble, however results are far from conclusive in this area and other studies show the exact opposite.

High doses of stearic acid have been found to suppress the action of the immune system's T-cells (a type of lymphocyte/white blood cell). However the required dosage to achieve these toxicity levels would be approximately 14.5g per day of Magnesium Stearate. Assuming a Magnesium Stearate content of between 1-5% of total supplement mass as Magnesium Stearate, then for every 1000mg (1g) of supplement capsules, 10-50mg would be Magnesium Stearate.

Total Mass Mg(C18H35O2)2

1000mg 10mg
1450,000mg 14,500mg
1.45kg 14.5g

So in order to ingest 14.5g per day of Mg(C18H35O2)2, one would have to consume 290g to 1.45kg of capsule or tablet-based supplements, which for heavy users, is not inconceivable (assuming a higher Stearate concentration), but unlikely for capsules with a lower Stearate concentration.

www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1384169

Unfortunately, as it is not an 'active' ingredient, the actual amount of Magnesium Stearate or Stearic Acid is rarely ever listed on supplements ingredients. A statement from the manufacturer like the one above can be requested for each supplier of your supplements if desired.

Although Magnesium Stearate and Stearic Acid are regarded by the supplement and pharmaceutical industry as 'harmless', and the concentrations in supplements are relvatively low, excessive consumption may adversely affect the immune system and be a potential source of toxin contamination, so it is probably wise to restrict the number of tablets and capsules one consumes per day, as clearly the more one takes, the more stearic acid and/or stearate one consumes. If you do not consume a huge number, then it is no significant problem.

If one can buy a supplement in powder and capsule/tablet form, it is better to use the powder, even if it is less convenient. Powder form is also usually cheaper/more cost effective, requiring less ingredients, fillers and no capsule/tablet processing, getting more of the active ingredients for your money. Depending on the supplement, one may also need to take much less (mg of active ingredient) as it is more effectively absorbed, perhaps partly because of the lack of fillers and stearate/stearic acid coating. If you take a large number of supplements in powder form, you may elect to buy a set of digital mini scales, that go down to 0.1g or better still 0.001g or 1mg. I acquired a set of such scales for a cheap price from a company in Hong Kong. Some containers use a serving spoon or scoop for the serving suggestion amount, but if one wants to take much less then using scales or 'guesstimating' the right amount is an option (you may overdo it with the latter method).

Some manufacturers do not use Stearate/Stearic Acid as fillers, including Thorne Research, Renew Life and Christopher's Original Formulas. Always read the label or check the ingredients list before buying and make an informed decision! Why not look at the ingredients of teh supplements you currently own?

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Mineral Deficiencies:

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General:

A variety of elements may be deficient in a person with CFS or related conditions, but the most common are Magnesium and Selenium. Others essential and non-essential elements that may be in low include Calcium, Sodium, Potassium, Copper, Zinc, Manganese, Chromium, Vanadium, Molybdenum, Boron, Iodine, Lithium, Phosphorus, Strontium, Sulfur, Barium, Cobalt, Iron, Germanium, Rubidium and Zirconium. Low levels of each essential and non-essential element have a corresponding biochemical impact on the body. The levels of these essential and trace elements can be determined by means of a hair mineral analysis. The vast majority of CFS sufferers have a number of the above elements in moderate to chronically low levels. In addition, a high toxic burden of heavy metals will have a displacement effect on specific nutritional elements, worsening the effect still (for example, zinc). Please see the toxic and nutritional element chart on the toxicity page for further information. Low magnesium and vitamin B6 levels are frequently associated with those suffering from sleep disorders. Low zinc levels (often indicated by a high hair mineral level) are frequently associated with poor immune system function. Cobalt is derived from vitamin B12, and so a cobalt severe deficiency is often symptomatic of a severe B12 deficiency.

Poor digestive function, particurlarly low stomach acid and digestive enzyme production, as well as toxins on the inter- and intra-cellular membranes, may mean a person does not effectively absorb and extract all nutritional elements from consumed food and even supplements, for example magnesium, calcium and potassium and numerous trace elements. Another effect of insufficient stomach acid and enzyme production is the inability to extract and absorb vital nutritional elements from food and even supplements, for example magnesium, calcium, zinc or potassium.

Magnesium is vital for normal muscle contraction (and general function), bone health, maintenance of normal blood pressure (and optimal cardiac health), and many enzymatic reactions. It is critical to over 300 different enzymes reactions in the body. Magnesium is important in stabilising ATP. With a deficiency of Magnesium, the ATP becomes over-regulated or inhibited, resulting in low energy levels.

In addition, inefficient amino acid conversion can result in a vast number of biochemical problems - as amino acids are involved in many processes. Amino acids and the body's ability to break down protein and synthesise different amino acids (including processes like methylation) is essential in a huge number of bio-chemical processes in the body, besides building up tissue, including for example the synthesis of enzymes, hormones, neurotransmitters, antibodies, blood transport proteins and other vital types of protein; and in cellular energy production. Enzymes (protein-based) are not just used in digestion but different enzymes play a huge number of different roles in the body, for example, breaking down inflammation or antioxidants. A failure to break down proteins properly in the digestive tract and a failure to convert (specific) amino acids properly (in sufficient quantities) clearly has a huge effect on the biochemical and hormonal balance, and functioning and efficiency of many processes in the body.

Specifically relating to nutrient depletion, besides poor digestive function, inefficient amino acid conversion can lead to the wasting of vital amino acids in the kidneys into the urine, for example, Taurine, which is required to effectively transport minerals into the tissues and cells. Studies have shown that taurine levels in vegans are frequently significantly lower than in those eating meat and dairy products. Please see the Taurine section below and also Wikipedia for more information on Taurine.

http://en.wikipedia.org/wiki/Taurine

Frequent muscle cramps can be a sign of Potassium, Magnesium and/or to a lesser extent Sodium deficiency. Muscle or eyelid twitching can be a sign of Potassium, Calcium and/or Vitamin D deficiency (D deficiency resulting in slow uptake of Calcium).

Nutritional deficiences may also cause a number of adverse enegetic and biochemical effects in the body, including further impairment of the digestive system. Therefore, it is often necessary to address both types of deficiency through supplementation (of both minerals and vitamins, and additional transport amino acids such as taurine if required) before the body can 'naturally' take over and absorb nutrients effectively and produce enough stomach acid/digestive enzymes naturally and its nutrient levels are high enough. It is usually not sufficient to suppplement additional minerals to overcome one's mineral deficiencies. Chronic deficiencies should of course be addressed through immediate supplementation (and this is something that a CFS sufferer should identify and establish at the very beginning of any treatment programme) and using Betaine HCl to make up for the lack of stomach acid to help with digestion and extraction of the minerals and vitamins into the blood stream.

An article examining the beneficial effects of amino acid supplementation is shown at the link below.

Metametrix Institute: Treatment of Chronic Fatigue Syndrome with Specific Amino Acid Supplementation

Identification of which amino acids are not being converted properly can be achieved by a blood or urinary amino acid profile. Please see the Identification page for more information.

However, until the digestive system is functioning properly, and the diet is sufficiently nutritious and appropriate for the individual, and the excessive amounts of toxins and partial detoxification products have been removed from the inter- and intra-cellular membranes, supplementation will only make so much progress. And if neither the digestive system or mineral and vitamin deficiencies are addressed, it is likely that both will deteriorate further. It is rather like a catch 22 situation. In addition, in some individuals, a very difficult to digest diet is likely to add to the above problems. As discussed above, stimulation of the digestive system energetically and removal of the vast majority of toxins from the body is necessary to enable the body to fully absorb all the minerals and vitamins it actually requires and is deficient in. It is easy to see how many CFS cases remain unresolved if these both these areas are not addressed.

As a general rule, chelated forms of nutritional elements (e.g. metal anions bonded to organic molecules such as amino acids, e.g. citrate, gluconate, glycinate, malate etc.) are easier to absorb than inorganic forms (e.g. metallic oxides or metallic salts, e.g. carbonate). It is reputed that humate and fulvate salts of trace elements (extracted from soil) are highly effective delivery mechanisms for mineral supplementation and replacement as well as being excellent chelators (please see the Fulvic and Humic acid section on the Detox page for more information). However, this is not always true, depending on what element one is talking about and of course the individual (i.e. sodium chloride is an effective way of taking sodium). Sometimes, a mixture of different forms of the same element may be optimal for absorption and delivery to the tissues. An individual may be taking high levels of a particular metal supplement, e.g. zinc, but failing to elevate his cellular zinc levels over months of supplementation, as the form of zinc (e.g. zinc oxide) is not readily absorbable. I have personally found for Trace mineral elements that Picolinate is the optimal chelated form. I was muscle tested for various forms, and this form always seemed to work best with the body, e.g. Thorne Research's Manganese Picolinate, Molybdenum Picolinate, Chromium Picolinate, etc. The best form of Zinc he found was Zinc Picolinate, Gluconate or Citrate. Cobalt supplements are rare (only as found in Fulvic or Humic acids together with other soil minerals included trace heavy metals) and the most common supplemental source is Vitamin B12.

Please note that amino acids can be taken in their acid format, or as amino acid salts of a nutritional metal. For example, if one wishes to take 'butyrate', then one can either take butyric acid or for example calcium and magnesium butyrate. If one takes a chelated mineral supplement (i.e. an amino acid salt), for example, magnesium citrate, then this may result in a large amounts of citrate being consumed. Intake of disproportionately large amounts of certain amino acids may have no ill effect on the amino acid balance and conversion processes that take place in the body. Others however may put the body into imbalance with respect to certain amino acids, and their precursors or the amino acids they are normally converted to. An amino acid analysis should highlight any problems that would be occurring in the body.

Supplementation of essential and trace elements in accordance with those shown to be most chronically deficient (e.g. from hair mineral analysis report) can significantly assist progress in treating CFS or related conditions. There is certainly wisdom in increasing food types that contain the specific mineral that you are most deficient in, and some people may choose to rely on an excellent diet alone to replenish low mineral and vitamin levels. However, I would not personally recommend this. A combination of a readily digestible and nutritious diet combined with relevant mineral and vitamin supplementation is probably optimal.

A useful web site summarising the effects of vitamin and mineral deficiencies can be found at the link below.

www.something-fishy.org/dangers/vitamins.php

Magnesium and Zinc are important for mitochondrial function (the Krebs cycle for energy production). Potassium is important for proper adrenal function. In extremely deficient individuals, where oral supplementation (of the correct minerals in the right form and dosage) is not making much difference, then one's consultant may advise intravenous (IV) injections of minerals such as Magnesium Sulphate (concentration: 1g/2ml; typical dose: 2ml or 1g) and/or Zinc Sulphate (concentration: 100mg/10ml; typical dose: 10ml or 100mg), in combination with oral supplementation (e.g. Magnesium and Zinc) and transdermal application (e.g. Epsom salts cream or bath). It may be wise to take minerals orally such Magnesium and Zinc at different times (as opposed to taking them together) to improve absorption. Another form of Magnesium injection is Magnesium Chloride in the Myer's Cocktail (see below for details).

Manganese in combination with certain vitamins and minerals is essential for many biochemical reactions, including carbohydrate metabolism and energy production. Manganese deficiency is frequently relate to low blood sugar levels, ligamentous problems and reproductive dysfunction. Manganese is also involved in the synthesis of the body's own powerful antioxidants.

Iodine is essential to proper thyroid functioning, and low Sodium and Iodine levels are often associated with hypothyroidism. Sea kelp (extract) and seaweed (e.g. bladderwrack) are excellent, rich sources of iodine. A number of research articles about the health problems associated with low iodine levels can be found at the link below.

www.optimox.com/pics/Iodine/opt_Research_I.shtml

The article 'Clinical Experience with Inorganic Non-radioactive Iodine/Iodide' by David Brownstein, M.D. can be read at the link below. 94.7% of 500 of his patients tested (various conditions) were deficient in inorganic iodine. He also found a link between hypothyroidism, breast diseases and low iodine levels. In addition, he found that supplementing with iodine increased the rate of excretion of toxic halides of Bromide and Fluoride, as well as Mercury (actually chelating out Mercury from the tissues). The proliferation of fluoride and bromide intake from oral sources appears to inhibit the update of iodine from our diet.

www.optimox.com/pics/Iodine/IOD-09/IOD_09.htm

The ideal Calcium (Ca) to Magnesium (Mg) ratio is around 7:1. A Magnesium deficiency relative to Calcium (i.e. a very high Ca to Mg ratio) may cause calcium to precipitate out of solution and to be 'wasted', contributing to high urinary Calcium levels, Calcium deposition in the urinary tract and gallbladder (e.g. gallstone or mineral build up in gallbladder). Calcium absorption is greatly enhanced when the diet is high in the amino acids arginine, histidine and lysine. These proteins also help to reduce the acidity of tissues. Foods containing significant levels of these amino acids include soy beans, lean sausage, beef, skimmed milk, spare ribs (pork), lentils, heart, salami, ham, lamb, peanuts, bass, cod and Canadian bacon.

Calcium (essential mineral) and Strontium (trace element) supplements, if taken, should not be taken at the same time, as they compete with each other for absorption (when taken in high dosages). They should be taken at different times of the day. Natural dietary sources of Calcium tend to include trace amounts of Strontium also. Both minerals are involved in bone structure and Stronium adds strength to the predominantly Calcium structure of the bone, a little like a metal alloy can be stronger than iron. Both minerals tend to be very useful when taking during a chelation programme, especially when using EDTA to remove the heavy metal Lead. Lead (Pb) is a +2 charged element in ionic form. Calcium and Strontium are also +2 ions, but in a different periodic group to Lead. However, they do seem to be useful in displacing lead from proteins, when used in conjunction with a chelating agent such as EDTA. Calcium tends to be the most commonly used for this purpose (a protective mineral) but Strontium may be favoured over Calcium, depending on the proteins in question.

Sodium and Potassium are regulated by the adrenal glands. Efficient adrenal glandular activity is required to maintain a good balance of these electrolytes. The optimum ratio of Na to K is around 2.4:1, with a lower level being indicative of adrenal problems and a susceptibility to depression, tension and phobias.

Low Sodium (Na) levels are often associated with reduced adrenal activity. Production of stomach acid (HCl) is dependent on sufficient Na levels.

A high Calcium to Potassium ratio is often associated with an underactive thyroid gland with fatigue being a common symptom. The ideal ratio of Ca to K is 2.4:1.

The golden rule when it comes to overcoming mineral deficiencies (or CFS in general) is to NEVER ASSUME ANYTHING! Your mineral levels are not static and can go up and down. Don't assume that all the relevant levels will keep going up or stay the same. They may go down. If you don't improve the quality of your digestion, even though you are supplementing various minerals, taking betaine HCl and have a good diet, you may find that many of your mineral levels continue to drop. Anyone attempting to overcome mineral deficiencies should really have a hair mineral analysis performed AT LEAST every six months. If you have digestive problems, it is advisable to have a urine test performed (e.g. Amino Acid Analysis Report) and to explore other factors that may be contributing to your digestive/nutritional problems, e.g. diet, stress, etc. It is not advisable to simply take a certain dosage of a particular mineral you are deficient in, and stop after a month or so because you lose interest and assume your levels are normal again! It may take anywhere between a month and a couple of years to get mineral levels back to normal, depending on the element one is talking about. Cellular trace elements are usually easier to replenish and get back to normal levels than essential nutritional mineral levels, because of the vast difference in daily quantity required. The daily requirement for Potassium for example is around 2g a day! Taking a 100mg supplement if you are chronically short of Potassium is neither here nor there. It is best to seek advice from a skilled medical practitioner in dosing minerals and vitamin levels.

Minerals levels are difficult to measure in a meaningful manner. Each sample for each specific mineral ideally needs to be a different source, e.g. red blood cell magnesium levels; or white blood cell zinc levels. Most mineral tests test for a variety of mineral sources from one place, which does not tell you anything necessarily about the mineral levels in the critical places where those minerals are most heavily utilised. In addition, one's mineral levels according to a particular type of test may be considered to be 'normal' for the population as a whole, but you could still have abnormal organic and amino metabolite results even though your levels were ÒnormalÓ. This is why in many cases, deducing what mineral and vitamin levels are inadequate or deficient based on the metabolic by-products that collect in the urine (e.g. amino acids or organic acids) may be a useful diagnostic tool. Measurement of these by-products in the blood and saliva is also possible. For example, I had had a hair mineral analysis test performed, and it showed that Magnesium levels were virtually normal (in the hair). But an amino acid profile (urine) showed that Asparagine was very low indicating that Magnesium was deficient in the tissues.

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Sodium:

Sodium is a crucial electrolyte involved in maintaining blood pressure and together with K+ and Cl- it regulate the fluids and acid-base balance in the body. It is also involved with nerve transmission and muscle contraction, including the regulation of the heart beat. Sodium helps to stimulate the Thyroid gland as well as compensate for any Sodium loss through adrenal gland underactivity (low Aldosterone results in excess fluid and electrolyte loss through frequent urination). Sodium also helps to stimulate the adrenal glands to some degree.

The minimum daily adult requirement for Sodium is 500mg or 0.5g. The US RDA is to consume less than 2.4g of Sodium per day. The UK allowance is 1.6g per day. 39% of the weight of Sodium Chloride is Sodium. Table salt or sea salt are almost entirely Sodium Chloride. Taking too much Sodium can result in raised blood pressure, palpitations and Potassium depletion.

Sodium deficiency can occur usually through sweating and/or (prolonged) diarrhea. Under normal circumstances dietary sources of Sodium are sufficient. Signs of Sodium depletion or deficiency include decreased blood pressure, weakness, apathy, nausea and muscle cramps in the extremeties, particularly the legs.

www.healthvitaminsguide.com/minerals/sodium.htm

If one is deficient in Sodium, it often follows that one is also deficient in the other essential minerals, such as calcium and magnesium. A good way of introducing more sodium into the diet is to take Himalayan Crystal Salt. A convenient way to take this is to clean out a screw top jar, then pour mineral water into it and place a few rocks of Himalayan Crystal Salt into it. Screw the top on. Leave out exposed to natural sunlight. Leave over night. Then take 1-2 dessert spoons (10ml) each morning. Leave the jar out in the kitchen or wherever, in natural light, indefinitely. The solution should always be saturated, i.e. there should always be excess crystals in the pot. As the crystal levels get low, add more crystals. As the water level gets low, add more mineral water. The mixture is generally known as Sole, pronounced 'so-lay', and has various benefits other than its sodium content.

If one considers the Sodium Chloride content of a saturated solution to be 26.4% salt by weight at room temperature (60F or 15C). The density of water is 1kg/litre. The salt concentration of 26.4% is therefore 0.26kg/l or 260g/l. One 10ml dessert spoon is 1/100th of a litre (1000ml), so the amount of Sodium Chloride in one 10ml dessert spoon = 260/100 = 2.6g. The daily recommended maximum intake for a 'normal' person is approximately 7g of salt. Bear in mind that those with CFS may be deficient in Sodium on account of poor absorption, so one's daily intake may need to be more than 7g per day. Consult with your medical practitioner and discuss your mineral level test results and any recommended action.

Suppliers of Himalayan Crystal Salt can be found on the links page. The Sole recipe can be found on the recipes page. Himalayan Crystal salt can also be used in the bath, but it may prove cost prohibitive! Ordinary table salt could perhaps be used instead although ideal.

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Potassium:

Potassium is a nutritional metal element that is required in large quantities by the body. It is associated with adrenal function, cardiac function and energy production. One sign of deficiency is muscle twitching (also a sign of Calcium deficiency), cardiac arrhythmia (tachycardia) and muscle weakness. The minimum RDA is 3.5g per day. The good news is that there are many dietary sources generally rich in potassium. Because such large amounts are required, chelated Potassium supplementation is helpful but the main effort should be focussed on Potassium-rich foods.

In the USA the FDA has limited K supplements to 3% of RDA per capsule or serving (too high K intake can lead to heart or kidney damage), so one would have to take a large number of capsules to maintain one's RDA or above if one is deficient. However this is not the case outside of the USA. e.g. The US brand Jarrow Formulas Potassium Citrate contains 99mg of elemental Potassium (from 264mg of Potassium Citrate) per tablet. The UK brand Archturus Potassium Citrate contains 266mg of elemental Potassium per capsule. Clearly one has to be careful when switching from one brand to another. The best supplemental source of K is probably Potassium Citrate, Glycinate or Gluconate. One may want to be careful with high intake of Citrate however as it appears to encourage yeast growth. Other supplemental sources of K include Potassium Bicarbonate (1g K per 1/2 tsp), Dead Sea Salts (2% K, ideal for baths or footbaths) or Diatomaceous Earth (also 2% K).

Potassium is absorbed both in the small intestine and colon. The luminal concentration must be above 25mEq/L for net absorption to take place, which is why Potassium deficiency often develops during periods of loose stools and diarrhea (with excess water in the stools reducing K concentrations).

It is possible to be supplementing, for example, a Potassium chelate, every day, and eat a diet relatively high in Potassium, but have one's cellular levels of Potassium drop. The reasons for this could be the lack of an efficient transport mechanism to get the mineral into one's cells and also excessive stress which can lead to mineral wasting. It could also be due to certain detoxification protocols such as chelation or FIR sauna usage that tend to deplete minerals in general, but mainly Potassium and Magnesium. One classic sign of Potassium loss/deficiency is random muscle twitching, for example in the eye lids or limbs.

Potassium-rich foods include:

- Potato or Sweet Potato
- Apricots
- Bananas and Plantains
- Bran
- Spinach
- Winter Squash
- Raisins
- Prunes
- Almonds
- Pinto Beans
- Kidney Beans
- Lentils
- Artichoke
- Figs
- Melon, esp. Cantaloupe and Honeydew

Diatomaceous Earth and also Dead Sea Salts are also rich in Potassium (containing typically 2%).

www.fatfreekitchen.com/nutrition/potassium.html

www.weightlossforall.com/potassium-rich-food.htm

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Calcium:

Calcium is a nutritional element required in modest quantities by the body. It is associated with bone formation, cardiac function, muscle development, protecting against blood clotting, nervous system function and enzyme function etc. It is also associated with Nitric Oxide production, and excessive Ca2+ results in increased Nitric Oxide production, which can be problematic if there is elevated free radical production. See the Peroxynitrite page for more information. The adult requirement for Ca2+ is 1000mg or 1g per day. A deficiency in Calcium can result in muscle cramping, muscle spasms, muscle ache, muscle twitching, eye twitching, jaw pain, tingling or numbness in the hands and feet, and long term, can result in osteoporosis. High Calcium levels in a hair mineral analysis test often means one is wasting Calcium, i.e. that one is deficient in Calcium, rather than having too much. In rare cases it does actually mean that one's Ca2+ levels are too high. Many practitioners advise against Calcium supplementation as it can elevate chances of Kidney stone formation. Calcium supplements are best taken in chelated form, e.g. Calcium Citrate, or as 'Bone Calcium'. Bone Calcium is the general name for Microcrystalline Hydoxyapatite (MCH) a.k.a. Calcium Hydroxyapatite, which is rich in Calcium, Collagen and Vitamin D and other trace minerals to assist in Calcium utilisation. MCH is the actual form of Calcium naturally found in bone tissue. MCH is derived from animal sources, normally bovine. Many raw vegans actually recommend MCH as the best source of Calcium to take supplementally during juice fasts (which are notoriously low in Calcium intake)!

Calcium-rich foods include:

- Dairy Products, e.g. Yoghurt, Milk, Cream, Cheese
- Sardines
- Halibut
- Sesame Seeds
- Almonds
- Spinach and other green leafy vegetables
- Broccoli
- Kidney Beans
- Tofu
- Figs
- Prunes
- Oats
- Algas Calcareas (South American marine plant)

Diatomaceous Earth is also rich in Calcium (containing typically 5%).

According to Ron Lagerquist in his book'North American Diet', a diet excessively high in Protein and Dairy products may deplete Calcium levels, on account of the acidity produced by digesting large quantities of proteins (Calcium and other compounds required to raise the blood pH) and excessive Urea excretion by the kidneys (resulting in mineral depletion in general through excessive urination and the potential for kidney stone development). In addition, low fat milk may render the Calcium less absorbable as the Calcium is best absorbed with fat. Pasturisation also destroys the enzymes that can render the Calcium in milk more readily available to the body. So although pasturised dairy may contain high levels of Calcium, it may not be readily absorbed by the body.

www.freedomyou.com/nutrition_book/Milk%20and%20Cookies.htm

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Magnesium:

Magnesium RDA is 300-400mg per day. In those with CFS or related conditions, the actual requirement may be many times higher than this. Symptoms of Magnesium deficiency may include fatigue, insomnia and/or muscle cramps. Magnesium deficiency is one of the most common mineral deficiencies in the world today, and especially in those with poor health.m

Magnesium displacement is also a problem in those with heavy metal toxicity. Your exact magnesium level requirements can be ascertained quite easily. Taking more magnesium than the body can absorb in the short term is not harmful and merely results in diahorrea. The excess magnesium simples passes through the digestive system and draws in water from the blood stream. With higher and higher levels of magnesium, the faeces become gradually softer and softer until an explosive diahorrea occurs. This principle is used in many colon cleansing products, which aim to remove mucoid plaque and faeces build up by flushing out the colon. They often contain oxygen releasing chemicals which help to kill off your beneficial bacteria too, which is not a good thing. And they are usually very expensive.

What we are suggesting here is that you may want to consider taking an absorbable form of magnesium (the form your body can most readily absorb may vary over time and between individuals, but most commonly it is a chelated (organic) form of Magnesium such as Magnesium Glycinate, Aspartate or Citrate, with some added Magnesium Oxide (an inorganic form of Mg). Magnesium Chloride (MgCl2) is an inorganic form of Mg but is reputed to be highly absorbable. One particularly bioavailable form of MgCl2 is dissolved in an oil emulsion base, and marketed as 'Magnesium Oil'. This can be poured into a cup of herbal tea or hot water and drunk when cool enough, for example. See further below for more information.

When first starting Mg supplementation, perhaps slowly increase your daily dosage of Magnesium over a period of time, until you reach the point of diahorrea. At this point, back off slightly, and then you have found your maximum/optimal amount of magnesium to take - when the stool is not too soft (too soft and you risk not absorbing bulk and trace minerals from stool in your colon). Of course, you should not take your daily dosage of magnesium all in one go, as the body can clearly not absorb it all, and you will experience diahorrea. It is best to take as little as possible as many times a day as possible. You may find that you can take a couple of hundred milligrams at a time without experiencing diahorrea, it may be slightly more, it may be slightly less. You need to find what works best for you. You may find taking small dosages every hour or every two hours works well for you. The reaction of diahorrea to too much magnesium may not come immediately, it may come the next day, so you may have to wait a day until you know your day's dosage was alright. If you are taking anything that is laxative in nature, such as Aloe Vera juice, this may induce diahorrea early in your magnesium supplementation programme.

When you first start this regime, as you slowly increase your daily dosage, you may feel totally wired and experience feelings of euphoria at levels of 400-500% of the RDA per day. This in general terms is a signal from the body that it has been absolutely desperate for this mineral for years, and now it is getting exactly what it wants. Of course, in this instance there is no short term negative effect, unlike drugs which may make you feel temporarily euphoric, but wreak havoc with your physiology, not to mention your mind. However, this is more a short term strategy rather than long term strategy. You may notice that initially when trying such a regime the amount your body can absorb peaks in the first few hours or day of such a regime, but that after that you have to rapidly cut back the dosage. This type of strategy is really optimal for short bursts, a day or two at a time, to be employed as and when necessary. If you are regularly having loose stools on account of excess Magnesium and Potassium intake, then of course because less water is being absorbed from your digestive tract, the digestive tract may tend to bloat, giving you a bloated looking belly. Clearly digestion takes places best when the electrolyte balance is normal and there is a normal amount of fluid in the digestive tract, as an excess dilutes the effects of the various enzymes and carrier proteins, and may affect absorption of nutrients in general. Long term it is best to supplement in a moderate fashion, to support the body, rather than flood it with very high concentrations of certain minerals, which may cause mineral level imbalances (e.g. mineral ratios) and problems relating to these. Mineral ratios are discussed above.

So start slowly with small amounts at a time, and gradually increase the number of times a day you take it over a week or two until you find your 'optimum' (or more accurately maximum) level. Over a period of weeks, the body will gradually make up for its magnesium deficit, and the actual amount you need to take will slowly decrease over time. You will notice this by taking the same amount each day, and one day getting diahorrea. This is the signal to reduce the dosage slightly. You may also find that you can still take the same daily amount of magnesium happily, but that you need to break it up into smaller individual dosages during the day to avoid diahorrea. In general terms, the amount you can take per day and per dosage will decrease over time. So what you are effectively doing is finding the optimum balance and dosage/dosage frequency of magnesium to achieve the maximum rate of absorption of magnesium whilst respecting the digestive system and ensuring that your stools do not become too loose, adapting your dosage/dosage frequency with time in accordance with your body's needs. An example of a good magnesium supplement are Nutri's Ultra Muscleze, Vital Nutrients' Triple Mag and Jarrow Formulas' Magnesium Optimiser. You may wish to try a couple of different high quality Magnesium supplements or your naturopath/consultant can assist you in finding the particular supplement that works best for your body using kinesiology. After a certain point in your treatment, once you have significantly reduced the magnesium deficiency in your tissues, your naturopath/consultant may determine that your body no longer requires the maximum dosage of magnesium, and requires a slightly lower dosage.

If you are taking a magnesium supplement which contains malic acid, then you may not to alternate with a magnesium product that does not contain it perhaps every month or two, as it may create a little balance in the Krebs cycle for energy production (specifically the Citric Acid Cycle). Where malic acid levels are artificially elevated for prolonged periods, they may cause the body to convert less fumaric acid into malic acid (as there is little requirement), resulting in hugely elevated fumaric acid levels. You may notice this yourself, for example, a magnesium supplement in drink form that once tasted amazing, losing its zing and somehow has a taste that the body is telling you it doesn't want.

Taurine is an amino acid which is synergistic with magnesium delivery to the body's cells. Taurine is an ion and pH buffer in the heart, muscles and central nervous system. It is also a major constituent of bile. It is also a powerful antioxidant and antitoxin, particularly important to the liver and immune system. Taurine is also classified as a 'semi-essential nutrient'. If you are short of taurine (i.e. your urine levels of taurine are very high because your kidneys are 'wasting' it from the body), you will not absorb magnesium properly and you will 'waste' magnesium from the body. Please see the Taurine section below for more information. In addition, one cannot assume that just because one is supplementing magnesium and that one's hair, blood or urine magnesium levels are normal or slightly sub-normal, that one's actual cellular levels are adequate if the metabolic processes that rely on magnesium are not functioning properly (which can be measured and provide an indirect measurement or indicator of cellular Magnesium levels). Low Magnesium and Taurine levels have many adverse effects on the body. Many good magnesium supplements contain Taurine (such as Ultra Muscleze). L-Methionine is a precursor to Taurine which may also be taken to assist in nutrient assimilation. However, no amino acid supplementation should be undertaken without guidance from a qualified practitioner and a urine test (amino acid analysis profile). Taurine is defined below on Wikipedia.

http://en.wikipedia.org/wiki/Taurine

If you do take more than a couple of 100% RDA of magnesium in a day, (at one point I was taking a daily total of 1300%), then you may perhaps need to take additional betaine HCl tablets/capsules with your magnesium. This is because Mg is alkaline in nature and will neutralise your stomach acid. A rough guide is to take 400-700mg of betaine HCl with each magnesium dosage (300mg chelated Magnesium). If you are taking large amounts of magnesium and you do not do this, then you will experience large amounts of pungent wind, which is a sign of poor protein digestion (i.e. not enough stomach acid to break down the protein, leaving bad bacteria to break it down in the intestines.)

A supplementary way of taking magnesium is transdermally. Best performed daily if possible - instead of taking an oral Magnesium supplement, or in combination with. There are various ways to absorb Magnesium through your skin.

One is to put on a lotion, cream or oil that contains Magnesium.

Probably the most convenient option is to buy 'Magnesium Oil' which is essentially Magnesium Chloride (MgCl2) in an oil emulsion base, e.g. White Egret Pure Magnesium Oil spray. It is very runny, with a consistency like water, and so you only need a small amount in the palm of your hand to spread onto yourself. The White Egret Mg Oil is in a more convenient spray bottle and I found it to be superior (somewhat) to the Health and Wisdom Magnesium Oil. Try applying it onto an area that is stiff or sore, or anywhere you don't mind getting greasy temporarily, e.g. your belly. Some people recommend washing it off after a while but I think it's best to just leave it on. If you do repeated applications in the same area you may end up with a thin film of MgCl2 salt - this is not a big deal, you can simply wash it off or rub a little aloe vera gel etc. into that area to help dissolve it and absorb it into the skin.

There are commercially available creams and lotions that contain Mg salts in them. Some may contain Epsom salts (Magnesium Sulphate or Mg2SO4), e.g. Kirkman Laboratories' Magnesium Sulfate Cream. Epsom salts is also a good source of Sulphate, used by the liver. Dea Sea Salts lotion is another alternative, for example, Yarden J.Malki Products' Dead Sea Natural Mineral Body Lotion. Dea Sea Salt (Maris Sal) is chiefly comprised of Magnesium. It also has the added benefit of containing a variety of other minerals, including potassium. Yarden also offer shower cream and shampoo products.

You can also make your own epsom salts or dead sea salts cream by taking some skin cream and adding a small amount some concentrated epsom salts solution to it, a stir. If you add too much it will simply go watery. If you add epsom salt crystals to a tub of skin cream or a bottle of shower gel, it will also work, but you may need to stir it vigorously and leave it to dissolve for a few days. If you add too much salt it will precipitate out the constituents of the cream out of solution which is not what you want. If you make your own, and you use oil-based ingredients, like cocoa butter, you will need an emulsifier or you just end up with two layers, one of oil/fat and one of water. Emulsifiers oxidise over time too. It is not as easy as it sounds. Heating it gently on the stove may help it dissolve/mix temporarily. You can use oil-based lotions (e.g. cocoa butter), petroleum-based lotions or natural lotions (e.g. aloe vera gel). The latter is most prone to becoming too runny, and the former two are most prone to not mixing properly.

An alternative to oils, creams and lotions is to use dissolved Mg salts (e.g. Epsom salts or Dead Sea salts) in a bath or food bath (wide tub). A minimum of 2 tablespoons is usually recommended in a footbath (in a few cm of warm water), and up to 500g in a bath tub. Soak for around 20 minutes or more as long as your skin stays warm it will absorb the salt better than if cold with less blood flow. An alternative is to make a saturated solution by dissolving the salt in a mug of boiling water, mix it, allow to cool slightly and pour it over yourself in the shower - leaving the layer of saturated salt solution on yourself and sit/stand for around 10 minutes until it starts to get too thick, and then apply some more, and repeat. You will have saturated salt solution in contact with nearly all of your skin over your entire body so it is similar to an epsom salts bath in some respects - even if most of the liquid runs off the body.

Epsom Salts and Dead Sea Salts can be purchased from health supplement suppliers, on famous auction sites and from high street chemists. Cheapest to buy in bulk (e.g. a few kilos at a time).

Dead Sea Salts - a naturally occuring salt mixture - contains high levels of magnesium, e.g. 47%+ MgCl2 (Magnesium Chloride), <2.2% CaCl2 (Calcium Chloride), <0.8% NaCl (Sodium Chloride), <0.5% KCl (Potassium Chloride). Salt from other oceans by contrast is largely made up of Sodium Chloride, typically 97% of total salt concentration. Many people have reported health benefits from swimming in the Dead Sea, and it is likely that they were depleted in essential minerals, mainly Magnesium. It is likely if a sufferer of CFS wishes to go on holiday, that choosing a holiday by the Dead Sea may be of some benefit!

http://en.wikipedia.org/wiki/Dead_Sea_salt

Dead Sea salt varies by composition, but typically contains:

- 67.8% Chloride & Bromide
- 13.5% Magnesium
- 10.7% Sodium
- 5.1% Calcium
- 2.3% Potassium

Please note that supplementation of other minerals than magnesium is not that simple, and excessive blood and tissue levels may upset one's biochemical balance (more than excessive Mg supplementation) and cause problems with other mineral uptake and usage. The correct mineral ratios in the body are of critical importance. It is not recommended to supplement minerals without a hair mineral analysis and without recommendation from a qualified specialist.

Dietary sources of Magnesium are listed below.

http://en.wikipedia.org/wiki/Magnesium#Sources

'Spices, nuts [and seeds], cereals, coffee [also contains caffeine], cocoa [also contains theobromine - similar to caffeine], tea [also contains caffeine], and vegetables (especially green leafy ones) are rich sources of magnesium. Observations of reduced dietary magnesium intake in modern Western countries as compared to earlier generations may be related to food refining and modern fertilizers which contain no magnesium.'

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Zinc:

The RDA for Zinc in adults is approximately 8-11mg. The element zinc is used in over 100 enzymes involved in metabolic processes, including synthesis of RNA and DNA. It is involved in transport of Vitamin A from the liver, in forming the antioxidant enzyme SOD to protect cells from free radical damage, growth, development, reproduction health (e.g. maintaining Testerosterone levels) and the immune system (increasing T-lymphocyte counts and enhancing White Blood Cell (WBC) functions). The body contains typically 1.5-2.5g of Zinc.

Zinc is water-soluble and is lost in sweating and through food processing and cooking water (where the Zinc dissolves away). Vegetarian diets also tend to be low in Zinc (the oxalates in grains and vegetables binding to the Zinc and preventing absorption). Heavy metals such as Mercury also tend to displace Magnesium and Zinc from the proteins they are normally found in. There are no readily available pools or stores of Zinc in the body as such, so if Zinc absorption from the GI tract decreases or losses from GI tract, urine or skin increases, then Zn deficiency can quickly occur. Diarrhea is both a cause and result of Zinc deficiency. Too rapid movement of chyme/stool through the small and large intestine (i.e. short transit times) will result in greatly reduced levels of Zinc absorption, and indeed other nutritional elements.

As stated above, in a hair mineral analysis test, elevated zinc results usually indicate a zinc deficiency in the tissues, rather than high zinc levels.

Zinc deficiency is quite common in CFS and ME cases. Signs of Zinc deficiency include slow wound healing, reduced sense of taste or smell, immune system impairment, loss of appetite, reduced stomach aweight loss, impotence, strong body odour, depression, paranoia, acne, dermititis and reduced growth rates in minors.

www.acu-cell.com/znk.html

Food sources rich in Zinc include:

- Oysters
- Shellfish
- Brewer's Yeast
- Bran
- Pine Nuts
- Pecan Nuts
- Pumpkin Seeds
- Almonds
- Walnuts
- Brazil Nuts
- Liver
- Cashew Nuts
- Parmesan Cheese
- Fish
- Eggs
- Red Meat
- Poultry
- Artechoke
- Olives
- Sweet Potato
- Spinach
- Cauliflower
- Radish
- Peas
- Bananas
- Peaches
- Blackberries
- Kiwi Fruit
- Lima beans
- Soya beans
- Chickpeas
- Kidney beans
- White (baked) beans

http://lifestyle.iloveindia.com/lounge/zinc-rich-foods-3814.html

www.weightlossforall.com/foods-rich-zinc.htm

www.keepthedoctoraway.co.uk/Articles/LovelifeZinc_8.html

Zinc can be taken in supplemental form, probably best as Citrate or Gluconate. Examples include Vital Nutrients' Zinc Citrate capsules and Source Naturals' Wellness Zinc Lozenges (containing Zinc Gluconate and Ascorbate). Zinc is often supplemented during times of viral infection and works synergistically with the herb Echinacea in this respect.

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Iron:

'Iron is an essential mineral and an important component of proteins involved in oxygen transport and metabolism. Iron is also an essential cofactor in the synthesis of neurotransmitters such as dopamine, norepinephrine, and serotonin. About 15 percent of the body's iron is stored for future needs and mobilized when dietary intake is inadequate. The body usually maintains normal iron status by controlling the amount of iron absorbed from food. There are two forms of dietary iron: heme and non-heme. Sources of heme iron include meat fish and poultry. Sources of non-heme iron, which is not absorbed as well as heme iron, include beans, lentils, flours, cereals, and grain products. Other sources of iron include dried fruit, peas, asparagus, leafy greens, strawberries, and nuts.'

www.nlm.nih.gov/medlineplus/druginfo/natural/patient-iron.html

The amino acid L-Histidine plays a role in Iron storage, absorption and utilisation. L-Histidine is used in the Iron storage protein Ferritin, the iron uptake regulation protein FUR, the iron metabolism cofactor cerulplasmin, the SOD antioxidant enzyme (which protects mitochondria from free radical damage) and also makes up the part of the Hemoglobin molecule (Heme-based) that Iron binds most tightly to. If L-Histidine levels are low, then the subject in question may have problems absorbing and utilising iron, including a potentially low Hemoglobin count.

It has been observed in some patients who are suffering from a temporary fatigue that it is related to iron deficiency and/or anaemia. Iron deficiency is regarded as the most common form of nutritional deficiency by the WHO. Iron levels can be determined by a blood count, blood test or hair mineral analysis. Supplementation with iron or eating more iron rich foods will help to alleviate this condition.

http://en.wikipedia.org/wiki/Iron_deficiency_(medicine)

Anaemia is a condition that occurs when there are too few red blood cells (RBCs), i.e. less hemoglobin and less capability to absorb oxygen. A reduction in RBCs can occur is there is a reduction in the number of RBCs being produced or an increase in the loss of RBCs. RBCs are manufactured in the bone marrow, and have a life expectancy of approximately 4 months. The bone marrow requires iron, vitamin B12 and vitamin B9 (Folic Acid) in order to produce more red blood cells. Cases of cellular iron deficiency can lead to anaemia over time as RBC production will be impaired. Supplementation with these vitamins as well as sources of dietary iron can help to overcome anaemia and increase red blood cell production. Other nutrients necessary for cell production, i.e. sufficient protein and Essential Fatty Acids should also help and should be part of one's diet in any case. In addition, if there are any other biochemical issues present, for example, any amino acid imbalances, or other vitamin or mineral deficiencies, then these must also be addressed to ensure a full return to health.

www.netdoctor.co.uk/diseases/facts/anaemiab12.htm

The opposite of anaemia is haemochromatosis (aka hemochromatosis). The condition takes the form of excessive iron absorption of dietary sources of iron, resulting in a pathological increase in total bodily iron stores. Humans are unable to excrete excess iron. Excess iron tends to build up in the tissues and organs, including the brain, liver, pancreas, heart and adrenal glands, disrupting their normal function. Iron in high concentrations turns from being a nutritional element into a toxic element. This can result in fatigue amongst other symptoms mimmicking other diseases, as it has a psychological and neurological impact. Iron overload has also been connected to excessive parasite overgrowth, for example liver pathologies. Unnecessary/excessive iron supplementation is a leading cause of mortality in the under-6s. The hereditary form of the disease is thought to affect up to 20% of the population, mainly in Northern Europe.

http://en.wikipedia.org/wiki/Hemochromatosis

'Males are usually diagnosed after their forties and fifties, and women several decades later, owing to regular iron loss through menstruation (which ceases in menopause). The severity of clinical disease in the hereditary form varies considerably. There is evidence suggesting that hereditary haemochromatosis patients affected with other liver ailments such as hepatitis or alcoholic liver disease suffer worse liver disease than those with either condition alone. There are also juvenile forms of hereditary haemochromatosis that present in childhood with the same consequences of iron overload.'

In haemochromatosis cases, the tissue build up of iron can presumably be detected via a hair mineral analysis or otherwise blood nutritional element tests. The usual method of testing is to measure Ferritin, a protein found in blood serum which is manufacturered by the liver to bind iron. Those suffering from haemochromatosis should avoid all supplements containing iron and avoid foods that are particularly rich in iron. Certain chelation agents (normally used in heavy metal detoxification) can also be used to chelate out the excess Iron form the tissues (e.g. Inositol Hexaphosphate (IP6) or deferoxamine (DFO) etc.) Women can also lose iron (as well as other elements) during their monthly menstruation.

www.lef.org/protocols/prtcl-156c.shtml

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Vitamin Deficiencies:

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Vitamin Definition List:

Vitamin:      Definition:
A Retinol
A-Precursor Betacarotine
B1 Thiamin, a.k.a. Thiamine or Aneurin
Active B1 Thiamine Diphosphate (ThDP, TDP), a.k.a. Thiamine Pyrophosphate (TPP) or Cocarboxylase
B2 / G Riboflavin
Active B2 Flavin Mononucleotide (FMN) (a.k.a. Riboflavin-5-Phosphate), Flavin Adenine Dinucleotide (FAD)
B3 Niacin, Nicotinic Acid, Inositol HexaNicotinate (IN6?)
Active B3 Nicotinamide Adenine Dinucleotide (NAD+), NADH, Niacinamide (Nicotinamide)
B4 Adenine
B5 Pantothenic Acid, Pantothenate; Panthenol; Pantothenine (more bioactive)
B6 Pyridoxine HCl
Active B6 Pyridoxal-5-Phosphate (P5P)
B7 / H Biotin
B8 Inositol, Inositol Hexaphosphate (IP6), Inositol Hexanicotinate (IN6?)
B9 Folic Acid
Active B9 5-Methyl-tetrahydrofolate (5-MTHF); Methylene-THF (precursor/intermediate)
B10 Pteroylmonoglutamic acid
B11 / S Factor S
B12 Cobalamin, Cyanocobalamin (Cyano-B12)
Active B12 Methylcobalamin (Methyl-B12 or MeCbl), Adenosylcobalamin (Adenosyl-B12 or AdoCbl);
Hydroxocobalamin (Hydroxo-B12 or OHCbl) - precursor to Methyl- & Adenosyl-B12
Bp Choline
Bx Para-Aminobenzoic Acid (PABA)
C Ascorbic Acid, Ester-C Ascorbate
D2 Ergocalciferol (also referred to as Calciferol)
D3 Cholecalciferol (also referred to as Calciferol)
E Alpha-tocopherol, Gamma-tocopherol etc.
F Linoleic Acid (LA) , Alpha Linolenic Acid (ALA), Gamma Linolenic Acid (GLA), Arachadonic Acid (AA)
K Menadione, Phytomenadione
Active K2 Menaquinone-7 (MK-7)
P Bioflavinoids

Some of above compounds are amino acids etc. and not strictly vitamins, but have been ascribed abbreviated vitamin nomenclature.

Please note that:

1000g = 1kg
1000mg = 1g
1000ug = 1mg

1g is a gram. It can also be written as one gramme.

1ug is a microgram. It can also be written as a microgramme. It is abbreviated to 'u' for simplicity, but the actual character is not strictly alphabetical and has a 'tail' on the left hand side of the 'u'.

1 U (or iu) is 1 International Unit. This is the amount of a substance that has an agreed biological effect. Since each substance is different and has different properties and effects, the conversion factor to get from U to ug will vary per sustance. There is no hard and fast rule. It is best to consult the manufacturer's own unit conversion.

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Vitamins A, C & E:

People suffering from CFS or related conditions frequently are suffering from oxidative and free radical damage as a result of years of intrusion by foreign organisms, environmental toxification, heavy metals and toxins from fried foods etc. Antioxidant supplementation in such individuals is critical. Antioxidants include Selenium and Vitamins A, C and E. Antioxidants are also present in a variety of green leafy foods and algae.

It may not recommended to take more than the recommended daily dosage of Vitamin A (in the form of pre-formed Retinyl Palmitate), as it may cause osteoporosis over a number of years. This does not appear to be an issue with Beta-Carotene which is converted into (retinol) Vitamin A by the body as and when it is required (a provitamin). Too high a daily dosage of Beta-Carotene can make one's skin go orange after a while. This is the body's way of storing it. If this happens then simply reduce the dosage and normal colouration will return!)

Chris Masterjohn argues that high levels of Vitamin A intake are fine as long as it is taken in a natural form (i.e. Cod Liver Oil) and not a synthesized form, as in the former sources it is balanced Vitamin D and K.

www.cholesterol-and-health.com/Benefit-Of-Cod-Liver-Oil.html

Dr Jospeh Mercola warns of excessive Vitamin A levels in many commercial Cod Liver Oil supplements, with many having vitamin A and D actually added to them, on top of their naturally occurring amounts. Mercola believes that vitamin A deficiency is still a problem in developing countries, whereas in developed countries, it is much more uncommon and vitamin A toxicity is much more commonplace. To quote a cliche, always read the label!

http://articles.mercola.com/sites/articles/archive/2008/12/23/important-cod-liver-oil-update.aspx

Much higher amounts of C and E can be safely taken. Vitamin C is water soluble and can be safely taken in high doses. Ester-C is reputed to be a more bio-assimilable, less acidic form of Ascorbic Acid (Vitamin C). Natural sources rich in Vitamin C include Acerola berries and cereal grasses (discussed in the Antioxidant section below) and of course to a lesser extent citrus fruit. There is no toxic level of Vitmain C as such, as the body induces diahorrea when it has reached its maximum dosage, which is around 10g per day. Buffered Vitamin C (i.e. Ascorbate salts of usually Potassium, Magnesium and Calcium - with a more neutral pH) can also be used, and half of its weight is roughly the Ascorbate component. Clearly diarrhea will arrive sooner with Buffered Vitamin C because of all the Magnesium. Mega vitamin doses (of A, C and E) should only really be taken for short periods of time, for example during winter months. Vitamin C is however reputed to be a pro-oxidant at high levels which can result in DNA damage. Vitamin C is also a weak chelating agent of heavy metals and high doses in those who have large amounts of heavy metals circulating may result in over-detoxification symptoms. Where you choose to obtain your antioxidants from is your decision. Not all those with related conditions have any oxidant damage, but it is healthy to have a good intake of antioxidants for anti-ageing reasons.

Dr Martin Pall argues that natural sources of Vitamin E are far superior to synthetic sources with respect to scavenging rogue oxidant molecules such as Peroxynitrite. Gamma-tocopherol is one of few biologically active types of 8 different tocopherol found in Vitamin E. Supplementation of one form tends to lower other forms in the body. Thus it is better to supplement a natural source of Vitamin that is rich(er) in the Gamma-Tocopherol to aid rather than inhibit Peroxynitrite scavenging. Natural Tocopherol supplements rich in Gamma-Tocopherol are often known by the name 'Gamma E'.

It should be noted that whilst Vitamin E, as well as being a blood pressure lowering nutrient, also increases the strength of the heart beat. Dosages should be increased slowly as a rapid increase in dosage may temporarily elevate blood pressure. High dosages may increase symptoms of heart palpitations so you may need to find the dosage that works best for you. If one suffers from palpitations at night, whilst in the supine position, then one may elect to take one's dosage of Gamma E in the morning and possibly mid-afternoon only (avoiding the evening). Those who are suffering from Rheumatic Fever or Rheumatic Cardiac Disease (damaged valves in the heart muscle) should avoid dosages of over 100 IU per day. Vitamin E is a powerful peroxynitrite scavenger and NMDA inhibitor, lowering excitotoxicity. It may also help to recycle oxidised Glutathione into reduced Glutathione, as other antioxidants tend to do.

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Vitamin D and UV Light Exposure:

Vitamin D is a fat soluble vitamin. It occurs in two main forms D2 and D3. D2 (ergocalciferol) is derived from plant and fungal sources (in very low concentrations), whereas D3 (cholecalciferol) is found in sufficient quantities in cod liver oil and oily fish. If supplementated, it is best absorbed with oily type foods. D3 is also produced naturally by the human body, by exposure of the skin to UVB radiation, the form that penetrates only the epidermal layers of the skin. Only a specific range of UVB is used by 7-Dehydrocholesterol in Vitamin D synthesis (270-300nm). Please note that UVA is not required and is harmful to human cells. UVB and UVC are also harmful, and penetrate further into the skin, but also have beneficial effects in small exposures.

http://en.wikipedia.org/wiki/Vitamin_D

'These wavelengths are present in sunlight when the UV index is greater than 3. At this solar elevation, which occurs daily within the tropics, daily during the spring and summer seasons in temperate regions, and almost never within the arctic circles, adequate amounts of vitamin D3 can be made in the skin after only ten to fifteen minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen. With longer exposure to UVB rays, an equilibrium is achieved in the skin, and the vitamin simply degrades as fast as it is generated'

'Exposure to sunlight for extended periods of time does not cause vitamin D toxicity. This is because within about 20 minutes of ultraviolet exposure in light skinned individuals (3-6 times longer for pigmented skin) the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded. Maximum endogenous production with full body exposure to sunlight is 250 µg (10,000 IU) per day.'

'Too little UVB radiation leads to a lack of Vitamin D. Too much UVB radiation leads to direct DNA damages and sunburn. An appropriate amount of UVB (which varies according to skin color) leads to a limited amount of direct DNA damage. This is recognized and repaired by the body. Then the melanin production is increased which leads to a long lasting tan. This tan occurs with a 2 day lag phase after irradiation, but it is much less harmful and long lasting than the one obtained from UVA. However some tanning lotions and sprays available in the market doesn't require UV exposition.'

'Exposure to UVB light, particularly the 310 nm narrowband UVB range, is an effective long-term treatment for many skin conditions like psoriasis, vitiligo, eczema, and others. UVB phototherapy does not require additional medications or topical preparations for the therapeutic benefit; only the light exposure is needed. However, phototherapy can be effective when used in conjunction with certain topical treatments such as anthralin, coal tar, and Vitamin A and D derivatives, or systemic treatments such as methotrexate and soriatane.'

The wavelengths of Ultraviolet (UV) light are cited below.

UVA (long wave or black light): 400 - 315 nm
UVB (medium wave): 315 - 280 nm
UVC (short wave or germicidal): 280 - 100 nm

98.7% of the UV radiation that reaches the ground is UVA, because of the ability of the planet's ozone layer (excluding the 'holes' in it) to absorb UV light, in particular UVB and UVC.

http://en.wikipedia.org/wiki/UV

'Ultraviolet (UV) irradiation present in sunlight is an environmental human carcinogen. The toxic effects of UV from natural sunlight and therapeutic artificial lamps are a major concern for human health. The major acute effects of UV irradiation on normal human skin comprise sunburn inflammation erythema, tanning, and local or systemic immunosuppression.'
- Matsumura and Ananthaswamy (2004)

'UVA, UVB and UVC can all damage collagen fibers and thereby accelerate aging of the skin. Both UVA and UVB destroy vitamin A in skin which may cause further damage. In the past UVA was considered less harmful, but today it is known that it can contribute to skin cancer via the indirect DNA damage (free radicals and reactive oxygen species). It penetrates deeply but it does not cause sunburn. UVA does not damage DNA directly like UVB and UVC, but it can generate highly reactive chemical intermediates, such as hydroxyl and oxygen radicals, which in turn can damage DNA. Because it does not cause reddening of the skin (erythema) it cannot be measured in the SPF testing. There is no good clinical measurement of the blocking of UVA radiation, but it is important that sunscreen block both UVA and UVB. Some scientists blame the absence of UVA filters in sunscreens for the higher melanoma-risk that was found for sunscreen users.'

'Some sunscreen lotions now include compounds such as titanium dioxide which helps protect against UVA rays. Other UVA blocking compounds found in sunscreen include zinc oxide and avobenzone. Cantaloupe extract, rich in the compound superoxide dismutase (SOD), can be bound with gliadin (the Gluten extract) to form glisodin, an orally-effective protectant against UVB radiation.'

Some commentators have criticised sunscreen lotion and sun cream manufacturers in their claims that using sun screen can help to prevent skin cancer, or lower one's risk of skin cancer, on the basis that using sun cream actually inhibits the body's own vitamin D production (when wearing the sun tan lotion) and vitamin D deficiency being one of many potential factors in causing cancer or ensuring its rapid spread throughout the body. However, this is a one sided argument, and whilst it may make a valid point about vitamin D production, it does not take into account daily exposure to the light at times when not wearing sun cream or indeed the excessive exposure to UV radiation that would otherwise occur. Whilst this could to some extent be mitigated by antioxidant supplementation, it will not prevent sunburn or premature ageing. However, one might argue that if one knew one was not going to wear sun cream, one would not be on the beach tanning all day. But one should bear in mind that many people are sunburnt whilst out in the sun for short periods of time during the day, rather than sitting in the shade all day, and some exposure is unavoidable, hence sun tan lotion on the nose, face or shoulders being useful on occasion. It does not also take into account dietary factors, and assumes that sunbathers will not have a sufficient dietary intake of cod liver oil or oily fish.

http://en.wikipedia.org/wiki/Uv_index

'...excessive exposure [to UV] causes sunburn, eye damage such as cataracts, skin aging, and skin cancer. Public-health organizations recommend that people protect themselves (for example, by applying sunscreen to the skin and wearing a hat) when the UV index is 3 or higher;'

The UV index depends largely on the angle of the sun. The highest angle is always at solar noon (not the same as time zone noon). Your local weather forecast or weather web site can provide you with a UV Index rating for your exact geographical location. The Met Office's UV Index forecast map for the UK can be found at the link below.

www.metoffice.gov.uk/weather/uk/uk_forecast_uv.html

General recommendations for precautions according to the UV index are shown at the link below. At UV Index 3, there is 'little risk of harm from unprotected sun exposure' but the general recommendation is to 'Wear sunglasses and use sunscreen, cover the body with clothing and a hat, and seek shade around midday when the sun is most intense.' Skin damage is cumulative over one's life.

http://en.wikipedia.org/wiki/Uv_index#How_to_use_the_index

Clearly the risk of UV damage and the time it takes for the body to synthesize Vitamin D both depend on the extent of one's skin pigmentation.

http://info.cancerresearchuk.org/healthyliving/sunsmart/knowyourrisk/skintype

www.krippspharmacy.com/WhatsNew.htm#VitaminD

'One survey published in 2001 estimated office- and homebound Canadians and Americans spend 93 per cent of waking time in buildings or cars, both of which block ultraviolet light.'

The UV wavelengths 270-300nm (the shorter end of UVB and the longer end of UVC) are utilised by the 7-dehydrocholesterol in the skin to make Vitamin D, with optimum production taking place at 295-297nm. These wavelengths are present in natural, outside light when the UV index is greater than 3.

Joanna Owens, senior science information officer for Cancer Research, has stated that "A little bit of sun goes a long way. The amount of exposure you need to top up your Vitamin D is always less than the amount needed to tan or burn, which increases the risk of skin cancer"

www.krippspharmacy.com/WhatsNew.htm#VitaminD

'One survey published in 2001 estimated office- and homebound Canadians and Americans spend 93 per cent of waking time in buildings or cars, both of which block ultraviolet light.'

As stated above, the body regulates its natural Vitamin D production so it is impossible for the body to produce too much itself. However, it is possible to take too much orally, and Vitamin D is toxic in high dosages.

'The exact long-term safe dose of vitamin D is not entirely known, but dosages up to 250 micrograms (10,000 IU) /day in healthy adults are believed to be safe, and all known cases of vitamin D toxicity with hypercalcemia have involved intake of or over 1,000 micrograms (40,000 IU)/day.'

It is likely this threshold limit is not the same for all individuals and some individuals may well experience signs of toxicity at or slightly below this limit. For example, a friend of mine with a chronically low level of Vitamin D was prescribed 50,000IU of Vitamin D per week, or roughly 7000IU per day. Whilst below the 'safe' limit, this caused huge problems, including intestinal problems and even an inability to defecate properly for 6 months. It is more sensible in extreme cases to start with a slightly lower dosage, perhaps 1000IU per day or so, and build up if necessary. This friend of mine subsequently fared better with a Vitamin D emulsion product (oil in water emulsion with D3 oil dispersed microscopically for better absorption) rather than Vitamin D capsules. This may vary from individual to individual. An example of a Vitamin D emulsion product is Biotics Research Bio-D-Mulsion, containing 400IU of D3 cholecalciferol per drop.

Please see the Hormone and Neurotransmitter page for more discussion regarding sufficient exposure to light.

There is significant evidence that sufficient quantities/availability of Vitamin D can help with proper immune system dysfunction, and conversely, Vitamin D deficiency can result in immune system dysfunction.

www.meresearch.org.uk/research/projects/vitamind.html

Mercola's comments on Vitamin D and Immune System Function

There is also some evidence to suggest that Vitamin D deficiency is more common than we might expect, and that it is linked to a number of disorders and conditions. Vitamin D supplementation is used to help fight cancer.

http://articles.mercola.com/sites/articles/archive/2008/12/27/important-vitamin-d-update.aspx

The relationship between vitamin D deficiency, immune system suppression and mycoplasma infections is explored on the Bacterial Overgrowth page.

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B Vitamins - General:

All B-Vitamins are usually very low in those with CFS or related conditions, in particular B6, B7, B9 and B12. B-vitamins in general are very low in our western diets. B-vitamins in general are highly (water) soluble, and levels can therefore drop off very quickly. Years of shortage and inefficient absorption may result in B-vitamin deficiencies of astonomical scale! Vitamins B12, B7 (folic acid) and B6 are required for methylation processes in the body (addition of a carbon atom to a carbon chain), in particular concerned with the production of stomach acid and amino acid conversion.

All B-vitamins are involved in metabolism and a deficiency in any one can result in a variety of biochemical and metabolic problems. In addition, B-vitamins are absorbed enzymatically from the digestive tract, rather than just relying on osmosis, and individuals with CFS often have inadequate number of or inactive enzymes responsible for such absorption for specific B-vitamins; let alone the necessary nutrients and sufficient enzymatic activity for the conversion of the synthetic forms or naturally occurring forms in food into the active, coenzymatic forms of these vitamins required by the cells of the body. Many enzymatic reactions are catalysed by intracellular Magnesium which is often very low in CFS cases. This is why many individuals with CFS, despite taking large quantities of B-vitamins, are not able to effectively absorb them or utilise them.

To understand the importance of B-vitamins, please see the Homocysteine Metabolism and Glutathione production section below, the Iron and Red Blood Cell Production section above, and also the Neurotransmitter (Stress Hormone) Production page and Mitochondrial Function page, as B-vitamins play a vital role in these processes. The importance of sufficient B-vitamins and availability cannot be stated enough in CFS cases.

Paul Cheney argues that it is better to take the vitamin in the form the body actually uses, rather than its precursor, as the body requires energy to convert them, and amino acid and other chemical conversion in the body in a CFS patient is already flawed, i.e. better to take folate rather than folic acid, as the body has to convert folic acid to folate (requiring ATP which is in short supply). This is something that I am in agreement with, particularly for chronic cases, ATP being only one requirement of several for converting a B-vitamin from it's consumed form to its active form, often involving a series of biochemical steps. These additional conversion steps can easily be bypassed with the supplemental B-vitamins at least, rendering them immediately bio-available and ready to take part in essential bodily enzymatic biochemical reactions - in theory.

In 2009, Paul Cheney changed his views on certain B-vitamins, suggesting that active forms of Folic acid and B12 were likely to be 'toxic' to CFS patients as a whole. Clearly this is not entirely the case, but a minority of patients do seem to react badly to even the active forms of certain B-vitamins (if taken daily but not when taken a few days apart when they have a beneficial effect). Whether this is a candida/bad bacteria issue or an oxidative stress and SOD/Glutathione issue is uncertain. The exact cause in such individuals may vary from person to person. One such individual claims not to experience problems with B-vitamins if ingested in natural food-source forms, but does experience problems with B-vitamin supplements, active or non-active forms, and only takes the latter every few days; but strangely does not suffer these effects with synthetic supplements if he had not rested properly during the night. Whether this is an issue with the form of the vitamins or the amounts is not certain. The vast majority of CFS patients however seem to react positively to supplementing those B-vitamins which are low, in a variety of forms (synthetic or food-sourced). More information about Cheney's latest 2009 theories can be seen on the Cardiac Insufficiency page.

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Thiamin (B1):

Vitamin B1, a.k.a. Thiamine, Thiamin or Aneurin, (Thiamin) performs many critical functions in the body and is not infrequently low in sufferers of CFS or related conditions. It contributes to the healthy functioning of the brain, muscles and nervous system. It is essential for energy, carbohydrate, protein and fat metabolism, and acts as a coenzyme in vital cellular reactions. Most thiamine is serum is bound to proteins, mainly albumin. 90% of thiamine in blood is in Red Blood Cells (RBCs).
B Whilst supplemental Thiamine is generally in the form of free Thiamine, and is the transport form of B1, there are 4 other types of Thiamine, which are phosphorylated enzymatically.

Thiamine Monophosphate (ThMP) has no known physiological role and is a transport form of Thiamine, and intermediate form of Thiamine.

Thiamine Diphosphate (ThDP, TDP), a.k.a. Thiamine Pyrophosphate (TPP) or Cocarboxylase is created enzymatically from Thiamine by the addition of ATP. ThDP is a coenzyme for several enzymes that catalyse the transfer of two carbon units and dehydrogenation of 2-xoxacids (alpha-keto acids). Several of these enzymes are involved in carbohydrate metabolism, and ATP production, as part of the Krebs cycle. ThDP also helps to remove excess lactic acid (a cause of muscle ache). ThDP is also a prerequisite for the production of one of the biologically active forms of Vitamin B3, NADPH, as well as the pentose sugars deoxyribose and ribose.

Thiamine Triphosphate (ThTP, TTP) is another biologically active form of Thiamine. It is thought to play a part in cell energy metabolism. It is also found in bacteria, fungi and plants as well as animals.

Adenosine Thiamine Triphosphate (AThTP) or thiaminylated ATP is a form of biologically active Thiamine found in E.coli, and to a lesser extent in yeast, roots of higher plants and animal tissue.

Approximately 80% of the Thiamine taken up by cells is phosphorylated and most is bound to proteins. ThMP and free (unphosphoylated) thiamine are present in plasma, milk, cerebrospinal fluid and extracellular fluids. Whilst the highly phosphorylated forms of Thiamine are unable to cross cell membranes, ThMP and free thiamine are. Thiamine and its metabolites are excreted in the urine (as with all other B-vitamins).

Other forms of Thiamine include Allithiamines. These are found naturally occurring in garlic, or more accurately speaking, formed when a garlic bulb is crushed - a disulphide derivative of Thiamine formed through enzymatic activity. Allithiamine was first discovered in Japan in 1951. It is a lipid-soluble form of Thiamine. Thiamine is water soluble, and so a lipid-soluble form can be more easiliy absorbed in cases of severe Thiamine deficiency.

One synthetic form of Allithiamine is Thiamine Tetrahydrofurfurl Disulfide (TTFD), which has many therapeutic uses in medicine, known to promote sulphation and support the immune system, as well as providing antioxidant properties. TTFD is also a mobilising agent for heavy metals, helping to release them from the tissues for excretion from the body. The disulfide group is believed to form a large part of its therapeutic action. TTFD is a useful form of Thiamine supplementation in Thiamine deficient individuals on account of its lipid-soluble properties. TTFD is sometimes referred to as Allithiamine. Please see the TTFD section on the Detoxification Protocols page for more information.

Another synthetic form of Allithiamine is Benfotiamine (S-benzyolthiamine-O-monophosphate or BTMP). According to Doctor's Best, it is fat-soluble and more physiologically active than Thiamin. It raises the blood levels of TPP and stimulates Transkotelease, a cellular enzyme essential for maintenance of normal glucose metabolic pathways.

Uptake of Thiamine is inhibited to some degree by a Folate (B9) deficiency. Thiamine deficiency can also be caused by malnutrition, a thiaminase rich diet (e.g. thermolabile thiaminases in raw freshwater fish, raw shellfish and ferns); by bacterial action (production of thiaminases); and/or excessive consumption of foods high in anti-thiamine factors (tea, coffee and betel nuts) or sulphite (e.g. pork products, wine etc.); but also poor absorption from the digestive tract associated with digestive disorders, chronic diseases, alcoholism and those who frequenly vomit.

Low levels can result in neurodegeneration, wasting and death. Low B1 levels have been observed in freshwater marine animals (e.g. Crocodiles) in disrupted ecosystems where gradual brain damage (brain death) has occurred, resulting in an inability to co-ordinate and control muscular movement, resulting in an inability to swim or move properly, and drowning. Thiamin is described on Wikipedia below.

http://en.wikipedia.org/wiki/Thiamin

Dietary sources of Thiamine are diverse and usually at low concentrations. foods with significant amounts of Thiamine include oats, flax, brown rice, whole grain rye, asparagus, kale, cauliflower, potatoes, oranges, liver (from beef, pork or chicken) and eggs. Pork meat and yeast (high in glutamate) are particularly rich sources of Thiamine.

As far as supplementation goes, in chronically ill cases, it more efficient to supplement with the biologically active Thiamin Diphosphate (a.k.a. ThDP, TDP, Thiamin Pyrophosphate, TPP or Cocarboxylase) than to use Thiamin. There is nothing to be gained for supplementing with both, and Thiamin requires processing enzymatically and energy before it can be utilised.

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Riboflavin (B2):

The name Riboflavin (E101), a.k.a. Vitamin B2, derives from 'ribose' and 'flavin'. Riboflavin is the central component of the enzymatic cofactors FAD and FMN, and is therefore required by all flavoproteins. Vitamin B2 is required for the metabolism of fats, ketone bodies, carbohydrates and proteins. FAD (as well as B3 as NADPH) is also involved in glutathione reductase production. FAD also reduces GSSG (oxidised form of Glutathione) to GSH (reduced form of Glutathione). B2 is involved in the Krebs Cycle, as a cofactor in Complex I and II. FAD is also involved in converting the amino acid Tryptophan into Niacin (B3). It is also involved in the conversion/synthesis of the coenzymatic forms of the B vitamins B6 (P5P) and B9 (5-MTHF), which are essential to methylation function.

http://en.wikipedia.org/wiki/Riboflavin

FAD is also involved in the synthesis of Catecholamines (adrenal neurotransmitters), specifically in the oxidation/deamination of the metabolite metanephrine by the enzyme monoamine oxidase (MAO) using FAD as a redox cofactor. FAD is also involved in the formation of VMA, in conjunction with the enzyme Aldehyde dehydrogenase and also iron, molybdenum and vitamin B3 (as NAD+).

Flavin Mononucleotide (FMN), a.k.a. Riboflavin-5'-Phosphate, is a biologically active, coenzyme form of B2. It is a phosphorylated form of Riboflavin. It is a precursor to FAD, the other biologically active form. FMN is the active form of B2 found in specialised supplements. The body manufacturers FMN by adding an ATP molecule to Riboflavin, to profuce FMN and ADP. This energy intensive reaction utilises the enzyme Riboflavin kinase.

http://en.wikipedia.org/wiki/Flavin_mononucleotide

'[FMN] functions as prosthetic group of various oxidoreductases including NADH dehydrogenase. During catalytic cycle, the reversible interconversion of oxidized (FMN), semiquinone (FMNH.) and reduced (FMNH2) forms occurs. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one and two electron transfers. It is the principal form in which riboflavin is found in cells and tissues. It requires more energy to produce, but is more soluble than riboflavin.'

FMN and FAD are cofactors that can carry one or two electrons, which makes them similar to Ubiquinone (Coenzyme Q10).

http://sandwalk.blogspot.com/2007/04/riboflavin-vitamin-b2-fmn-and-fad.html

Flavin Adenine Dinucleotide (FAD) is a redox factor involved in several important reactions in metabolism. It is a combination of flavin and adenosine diphosphate. It can exist in two different redox states, FAD and FADH2. FAD is reduced to FADH2 by accepting two hydrogen atoms (2 Hydrogen ions and 2 electrons). The reduced coenzyme FADH2 is an energy carrying molecule, and can be used as a substrate for oxidative phosphorylation in the mitochondria. FADH2 is oxidised back to FAD, producing enough of a proton gradient across the inner mitochondrial membrane for the ATP synthase enzyme to produce two units of ATP. The primary sources of reduced FAD are the Krebs cycle and the beta oxidation reaction pathways. In the Krebs cycle, FAD forms part of the succinate dehydrogenase enzyme that oxidises succinate to fumarate, whereas in its beta oxidation role it is a coenzyme in the reaction of acyl CoA dehydrogenase.

The redox reaction between FAD and FADH2 (in simplified form - only showing part of each molecule) can be seen at the link below.

http://en.wikipedia.org/wiki/FAD

Dietary sources of Riboflavin include milk, yoghurt, cottage cheese, leafy green vegetables, asparagus, bananas, persimmons, okra, chard, liver, kidneys, meat, eggs, fish, legumes (e.g. mature soybeans), yeast (also high in glutamate), mushrooms and almonds. Exposure to light destroys riboflavin.

Excess riboflavin is excreted in the urine. When taken in large oral dosages, it may turn the urine bright yellow (similar to excess beta carotene intake). Because of its yellow or yellow-orange colour, it is sometimes used as a food additive.

With regards to supplementation, Flavin MonoNucleotide (FMN) is the preferred type of B2, as it is biologically active and a precursor for FAD production, the other biologically active form of the vitamin. Riboflavin in itself serves no function, but only as a component of FMN or FAD. By supplementing with FMN it is possible for the body to utilise FMN directly, but also to convert it to FAD as required (saving an additional conversion step from Riboflavin).

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Niacin (B3):

Niacin, a.k.a. nicotinic acid or vitamin B, is a derivative of pyridine with an additional carboxyl group. Nicotinic acid was first discovered in 1873 during studies of the tobacco drug nicotine, where niacin was produced by oxidising nicotine with nitric acid. The name niacin originates from a combination of the words 'nicotinic acid' and 'vitamin'. Niacin deficiency can be caused by severe alcoholism.

http://en.wikipedia.org/wiki/Niacin

When administered in high oral dosages, e.g. 1.5-6.0g per day, Niacin can cause a condition known as 'flushing' where the skin may turn red, itch or 'burn'. This toxicological effect is as a byproduct of niacin's conversion to nicotinamide. High dosages of niacin can also cause indigestion, liver toxicity (fulminant hepatic failure - at over 2g per day), hyperglycemia (exaccerbating the effects of diabetes), hyperuricemia (may may exaccerbate the effects of gout). Such effects can be mitigated by taking slow release formulas or simply lowering the dosage.

Niacin has lipid modifying effects. In very high doses, e.g. 1-2g three times a day, can increase HDL cholesterol levels and lower VLDL levels (the precursor to LDL cholesterol). However this effect has resulted in birth defects in laboratory animals, although the effects on humans are not known.

Niacin is manufactured in the body from the amino acid tryptophan, although not in enough quantities for the body's requirements, and hence dietary sources are required.

Food sources of Niacin include liver, heat and kidney, chicken, beef, tuna, salmon, milk, eggs, avocados, dates, tomatoes, leafy vegetables, broccoli, carrots, sweet potatoes, asparagus, nuts, whole grains, legumes, saltbrush seeds, mushrooms and brewer's yeast (also high in glutamate). Breakfast cereals are usually supplemented with Niacin, but also contain sugar and are often not whole-grain.

Niacin can be obtained from protein as stated above, but it is dependent on efficient protein digestion and amino acid conversion in the body.

An alternative form of Niacin is Inositol Hexanicotinate, which is inositol (Vitamin B8) containing six niacin or nicotinic acid (B3) groups. It is marketed as a form of 'flush-free' or 'no flush' niacin, although it does not appear to have the same potency as niacin in terms of its positive (non-vitamin) effects, e.g. lowering LDL cholesterol.

http://en.wikipedia.org/wiki/Niacin#Inositol_hexanicotinate

Nicotinamide is the amide of nicotinic acid (B3). Niacin is the precursor to nicotinamide. The two are identical in their vitamin functions (i.e. subsequent conversion to NAD+, NADP etc.) with niacin requiring one additional step (i.e. conversion to nicotinamide). Nicotinamide also has anti-inflammatory effects. It also prevents immunosuppresion caused by UVA and UVB radiation.

http://en.wikipedia.org/wiki/Nicotinamide

Nicotinamide lacks the vasodilator, gastrointestinal, hepatic, and hypolipemic actions of nicotinic acid, and hence does not cause flushing. High dosages of nicotinamide are however toxic to the liver over 3g per day.

Nicotinamide Adenine Dinucleotide, a.k.a. NAD+, is a coenzyme found in all living cells. It is the biologically active form of Vitamin B3. NAD+ is involved in Catecholamine (adrenal neurotransmitter) synthesis and metabolism, specifically in producing the final metabolite VMA. NAD+ is an oxidising agent and electron acceptor, whereupon it becomes reduced into NADH (a reducing agent). NADH, a.k.a. Coenzyme-1, is a reducing agent able to donate electrons. NADH is basically NAD+ plus a Hydrogen ion and 2 electrons. NADH is sometimes referred to as Nicotinamide Adenine Dinucleotide plus high-energy Hydrogen, or even simply as Nicotinamide Adenine Dinucleotide (to confuse matters). In this manner, NAD+ and NADH are involved in a series of redox reactions, carrying electrons from one reaction to another. As both forms are used in these linked sets of reactions, each cells maintains approximately equal concentrations of NAD+ and NADH.

NADH plays an important role in the Krebs/Citric acid cycle for energy production in the mitochondria. NADH and NAD are an essential part of the ATP to ADP conversion.

http://dehydrogenase.org/NAD

http://en.wikipedia.org/wiki/Nicotinamide_Adenine_Dinucleotide

http://www.nadh-priceinfo.com/nadh_doctor_birkmayer_interview.cfm

When it comes to supplementation, both NAD+ and NADH forms of active B3 are available on the market. One could take the view that if one is going to supplement active B3, then one should take both forms in roughly equal quantities, to help maintain the 1:1 cellular ratio. However, some may debate the usefulness of this and state that it doesn't make any difference, as the body will automatically correct it and convert them to the desired ratio (electrically). Recent studies have speculated on possible reductive stress on the body on account of too much NADH supplementation - as there is insufficient O2 to oxidise it to NAD - as opposed to taking both NADH and NAD.

A typical dosage for a strong NAD(+) supplement is 20-25mg. A typical dosage for an NADH supplement is 5mg, although I have tried 10mg and 20mg versions by different manufacturers. High dosages of NADH can sometimes lead to NADH side effects of insomnia, anxiety, fatigue, and overstimulation, so if you experience such problems (more than usual if that is the case), then try reducing the dosage and try to feel the difference, to arrive at your optimum dosage - or have your practitioner use Applied Kinesiology testing on you to determine the dosage and frequency.

For example, I was muscle tested in June 2009 with both an NAD+ supplement (Coenzymated B-3 by Source Naturals) and an NADH supplement (by Natrol). The NAD+ supplement received a 'no opinion/does not care/nutrition' response (as well as certain other NADH brands) whereas the Natrol 20mg NADH supplement received a strong required/wanted response. Each individual will give a different response. I noticed myself that taking the Natrol 20mg NADH was much more effective than taking the Source Natural NAD supplement in a similar dosage. I have since tried a number of different NADH supplements, including Co-E1 NADH and Enada NADH, both of which are sold/granted under licence to various supplement manufacturers (see the ingredients for the type of NADH used), and none of these were particularly effective. Enada NADH is sold only in 5mg form, as it is considered the most powerful, but I did not find it be that useful for me personally. I was later muscle tested on Co-E1 NADH and the result was that it did 'nothing', i.e. a nutrition/food type response. Unfortunately Natrol has discontinued their NADH product (using Okepharm NADH aktiv). I tested a variety of other brands and has only found ProHealth Energy NADH to be comparable to the Natrol/Okepharm NADH. Many months later I managed to acquire a number of packets of Natrol NADH and at that point in time it did very little at all!

There are only a few laboratories that manufacture NADH, selling it in their own range of products, with other most brands producing or packaging it under licence. Manufacturers do not always state what source of NADH, so just because you buy another brand doesn't mean you aren't still taking the same source of NADH (i.e. if the source you tried isn't working for you very well). I have tried to formulate a list of different sources of NADH in the list below. Those he is unsure about (i.e. may just be selling someone else's NADH but not stating what it is on the label) , he has marked with a question mark.

Examples of NAD supplements include Source Naturals NAD and NOW Foods NAD.

As Niacin and Nicotinamide both perform other roles in the body besides its vitamin function, it may be wise to ensure one has some dietary and perhaps supplementary intake of niacin (either as niacin or inositol hexanicotinate) and nicotinamide as well, albeit in low dosages (certainly nowhere near the 1-2g mark where toxicity issues can result!)

The conenzyme, Nicotinamide Adenine Dinucleotide Phosphate (NADP+, a.k.a. TPN) is involved in anabolic reactions, like lipid and nucleic acid synthesis, which require NADPH, the reduced form of NADP+, to act as a reducing agent. NADP+ is chemically equivalent to NAD+ but with the addition of a phosphate group. This occurs by the addition of ATP to NAD+.

'The main function of NADP+ is as a reducing agent in anabolism, with this coenzyme being involved in pathways such as fatty acid synthesis and photosynthesis. Since NADPH is needed to drive redox reactions as a strong reducing agent, the NADP+/NADPH ratio is kept very low.'

http://en.wikipedia.org/wiki/Nadp

http://dehydrogenase.org/NADP

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Pantothenic Acid (B5):

Pantothenic Acid, or Vitamin B5, is a prerequisite for forming Coenzyme-A (CoA) and is critical in the metabolism and synthesis of carbohydrates, proteins and fats.

http://en.wikipedia.org/wiki/Pantothenic_acid

Small amounts of pantothenic acid are found in most food sources, but particularly concentrated in whole-grain cereals, legumes, meat, eggs and royal jelly. It is most commonly found as the Calcium salt of Pantothenic acid, Calcium Pantothenate, and also as the alcohol analog, provitamin panthenol. When ingested, it is quickly oxidised to pantothenate.

Pantethine is the dimeric form of pantothenic acid. It is a precursor to pantethine. It is an intermediate in the production of Coenzyme A by the body.

http://en.wikipedia.org/wiki/Pantethine

Pantethine is considered more biologically active and absorbable than pantothenic acid, but is less stable, and decomposes over time if not kept refrigerated. Most B5 supplements are therefore in the form of Pantothenate (a salt of Pantothenic acid).

www.nowfoods.com/Products/ProductsAlphabetically/M002799.htm

'Pantethine forms the reactive component of Coenzyme A (CoA) and the acyl-carrier protein (ACP). CoA and ACP are extensively involved in carbohydrate, lipid and amino acid metabolism. In addition to possessing the metabolic activity of pantothenic acid, Pantethine helps to support healthy serum lipid levels already within the normal range. Pantethine is also important for healthy cardiovascular function through its antioxidant activity.'

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Vitamin B6 and P5P:

There are various forms of vitamin B6. Those naturally occurring in food include pyridoxine (mainly from plant sources, e.g. whole grains, vegetables and nuts) and pyridoxal and pyridoxamine (mainly from meat and dairy sources). Pyridoxine is shown above. This is the most stable form which is most commonly used in B-vitamin supplements (often as Pyridoxine Hydrochloride (Pyridoxine HCl)).

There are additionally phosphate forms of the above vitamins. The phosphate form of pyridoxal is the metabolically active form of B6 used by the body in a variety of critical chemical reactions, and is known as Pyridoxal-5'-Phosphate (P-5-P or PLP). Pyridoxine is converted to P-5-P in the liver.

Studies have shown that P-5-P is 10 times more effective than Pyridoxine HCl. Absorption may be impaired in individuals with digestive problems. P-5-P is the form of B6 which is generally most efficient to supplement with P-5-P, as it is the active form, and pyridoxine serves no metabolic function (until converted to P-5-P).

http://www.vitasentials.com/p5p.htm

P5P is a co-factor in energy production and deficiency is most frequently associated with those with sleeping disorders. It is required in the body's melatonin/serotonin production cycle, and a chronic deficiency in B6/P5P may often result in the inability to stay asleep at night. It is involved in the metabolism of histamine. It is also required in amino acid metabolism, including transamination (a necessary step for gluconeogenesis - the enzmatic release of glucose from glycogen), deamination, decarboxylation, transsulphuration, selenoamino acid metabolism and for the conversion of tryptophan to Niacin (B3). P5P is the coenzyme required for proper function of the enzymes cystathionine synthase and cystathionase, which converted methionine into cysteine as part of homocysteine regulation and glutathione production. It also plays an indirect role in the biosynthesis of the Catecholamines (neurotransmitters) - adrenaline, noradrenaline and GABA (through the process of methylation). P5P is also involed in hemoglobin synthesis and function, through the synthesis of heme, and to enhance the oxygen binding of hemoglobin. It also plays a role in the absorption of amino acids in the digestive tract. Lastly, it is also involved in gene expression.

The amino acid L-Lysine is closely tied to P5P functionally, in terms of P5P's main function in transamination reaction, as Lysine is part of the aminotransferase enzyme. A deficiency of L-Lysine may result in an inability to utilise any available P5P fully and thus a functional P5P deficiency. An amino acid analysis should verify if Lysine levels are adequate or not.

Supplemental Vitamin B6 as pyroxidine is believed to worsen cases of Candida albicans whereas the active form P-5-P does not have this negative effect.

There are various P-5-P supplements, and P-5-P is by far the most effective way of supplementing B6, as opposed to the form pyroxidine, in cases where levels are chronically low. Some examples include Vital Nutrients Pyrixodal-5-Phosphate, Now Foods P-5-P and Nutri's Ultra-Muscleze (which contains a variety of minerals and vitamins including P-5-P). B6/P5P produces a temporary tingling and numbness in the fingers if taken in mega dosages over long periods, which disappears as soon as the dosage is lowered, and otherwise it is perfectly safe. The likelihood is however that the body will absorb whatever is thrown at it (in small amounts at a time of course). Otherwise the body will oxidise any excess as 4-pyridoxic acid (PA) which is the metabolite (waste product) excreted in the urine.

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Biotin (B7):

http://en.wikipedia.org/wiki/Biotin

Biotin, also known as Vitamin H or B7, has a variety of important functions in the body. It assists in the metabolism of carbohydrates (CHO) i.e. gluconeogenesis pathway (energy production in lieu of glucose when hungry or fasting); in fatty acid/lipid synthesis and oxidation/metabolism; in the metabolism of the amino acid leucine; in the synthesis of pancreatic (digestive) enzymes and also in the support of healthy hair and nail growth.

In these above functions, Biotin acts as an essential cofactor (co-enzyme) responsible for carbon dioxide (CO2) group transfer in several intracellular carboxylase enzymes (e.g. involved in posttranslational modification of glutamate residues in proteins). Biotin is associated with four different enzymes in humans:

www.chem.uwec.edu/Webpapers2001/barkacs/Pages/function.html

http://en.wikipedia.org/wiki/Gluconeogenesis

'Gluconeogenesis (abbreviated GNG) is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids.'

Tests on rat livers suggest that lipoic acid supplementation may reduce the activities of biotin-dependent carboxylase enzymes (responsible for amino acid conversion) in rats livers.

http://jn.nutrition.org/cgi/content/abstract/127/9/1776

Martin Pall in his book Explaining Unexplained Illnesses (discussed on the Nitric Oxide page) claims that it is well known that Lipoic Acid supplementation depletes Biotin levels, so if one is taking Lipoic Acid, one should also be taking supplemental Biotin. This is perhaps one reason why most ALA supplements contain the B-vitamin Biotin. This is also explained by manufacturers as helping to restore the activity of ALA. One should therefore consider additional supplementation with Biotin over and above what is found in Lipoic Acid supplements, if one believes one is potentially deficient or prone to deficiency (e.g. low levels of probiotic bacteria - which are responsible for the production of biotin required by the body as opposed to dietary sources).

Biotin is generally produced by our body's gut bacteria, which under normal circumstances produce more than our daily requirements. If one has a deficiency in probiotic but bacteria, then one may not produce enough biotin inside the GI tract. Dietary sources of biotin are very diverse and typically at very low concentrations. The best natural sources of biotin in food sources include liver, legume, soybeans, Swiss chard, tomatoes, romaine lettuce, and carrots, almonds, eggs, onions, cabbage, cucumber, cauliflower, goat's milk, cow's milk, raspberries, strawberries, halibut, oats, and walnuts. Highly concentrated sources of Biotin include Royal Jelly and Brewer's Yeast (also high in glutamate). Sufficient Biotin is generally produced by one's intestinal bacteria - which could be adversely affected by antibiotics etc.

Biotin is often found to be low in sufferers of CFS or related conditions. Deficiency may result in a loss of appetite. This is usually not a result of inadequate biotin intake, but a lack of the enzymes that process biotin. Approximately 50% of pregnant women are found to be deficient in biotin, and it may contribute to congenital malformations such as cleft palate.

Severe biotin deficiency can also be the result of a genetic mutation resulting in holocarboxylase synthase (HCS) deficiency, which is a lethal condition, remedied by very high daily dosages of biotin. However, it is very rare, typically affecting 1 in 200,000 newborn infants.

http://emedicine.medscape.com/article/944631-overview

I have myself suffered from biotin deficiency on two separate occasions, once in 2007 and once in latter half of 2009, focussing on other B-vitamins during that time, e.g. B6, B12 and Folic Acid. On the first occasion, there was a slight deficiency, corrected by supplementation with a high strength biotin supplement. On the subsequent occasion, the deficiency was very marked, and I was having problems with my energy levels and breaking out of a cycle of heart palpitations. Upon taking a similar Biotin supplement, I felt a warm sensation, not unlike a full body orgasm. The body in this instance really needed it and was showing it. I felt immediately better. Biotin deficienices should be corrected with biotin and probiotics supplementation.

An example of good Biotin supplements include Thorne Research Biotin-8 (8000mcg or 8mg - 2667%) or Now Foods Biotin 5000mcg.

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Inositol (B8) and IP6:

Vitamin B8, a.k.a. Inositol (or cis-1,2,3,5-trans-4,5-cyclohexanehexol), is a carbocyclic polyol that is used to form a number of secondary messengers (inositides) in eukaryotic cells, including inositol phosphates, phosphatidylinositol (PI) and phosphatidylinositol phosphate (PIP) lipids. These inositides and the phosphate forms of Inositol (discussed below) are active in cell-to-cell communication, including the transmission of nerve impulses. Affected tissues include the brain, liver and the muscles. Inositol is an indirect source of glucose and glucoronic acid, which are essential for liver detoxification.

It is found in many food sources, especially cereals with a high bran content (e.g. rice bran), nuts, beans and fruit (especially cantaloupe and oranges); and also in Lecithin (in the form Phosphatiyl Inositol). The most common naturally occurring form of inositol is myo-inositol (or myoinositol). Inositol is synthesised by the body and so is no longer considered a vitamin, although the quantities that it is synthesised in may not be sufficient for requirements, and one may need to rely on dietary or supplemental sources to supplement that created within the body.

http://en.wikipedia.org/wiki/Inositol

Inositol Hexakisphosphate (IP6), also known as Phytic Acid, or Phytate when in the salt form, is a form of Vitamin B8. It is the principle store of the element Phosphorus (P) in many plant tissues, especially bran and seeds. The denomination Phytates also includes the salts of related acids IP3 (Inositol Triphosphate), IP4 (Inositol Tetraphosphate) and IP5 (Inositol Pentaphosphate). As well as being a source of dietary Phosphorus, a vitamin promoting the immune system's natural NK-cells, and an antioxidant, it is also an excellent chelating agent.

It readily chelates Calcium and Magnesium in it's acid form. If taken in its salt form, i.e. Calcium-Magnesium Inositol Hexaphosphate, it is already combined with Calcium and Magnesium and will not chelate these out of the body. The salt form is therefore preferable to take as an oral supplement.

IP6 is used for chelating excess iron from the body in cases of haemochromatosis - there being no natural mechanism for removing excess iron from the body (besides menstruation in women). IP6 is also one of the few chelating agents used for Uranium removal, although I am sure that other natural chelators work well also.

IP6 is generally recommended to be taken on an empty stomach. It may be as well to ensure one is supplementing sufficient Calcium and Magnesium with meals also, and to ensure that one's Iron levels do not drop too much during the course of taking it, as this may result in various biochemical and cellular problems.

http://en.wikipedia.org/wiki/IP6

When Inositol and IP6 are taken together, they can form two molecules of IP3 in the body. IP3 is regarded by some as a superior form of taking Inositol and/or IP6, as it is ready to use as a nerve impulse communicator (i.e. in its active form). Of course, one would probably want to consume inositol in its basic form as well so that it can be converted into other inositides other than IP6.

www.ip6gold.com/product_info.html

An alternative form of Inositol (B8) is Inositol Hexanicotinate (IN6?), containing six niacin or nicotinic acid (B3) groups. It is marketed as a form of 'flush-free' or 'no flush' niacin, although it does not appear to have the same potency as niacin in terms of its positive (non-vitamin) effects, e.g. lowering LDL cholesterol.

http://en.wikipedia.org/wiki/Niacin#Inositol_hexanicotinate

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Folic Acid (B9):

The vitamin B9, Folic acid, shown above, is the synthetic form of the vitamin, found in many supplements. It is the non bio-active form, and must go through several conversion steps before it can be utilised by the body.

Methylfolate, also known as 5-MTHF, is the naturally occurring, biologically active form of B9. 5-MTHF is described in more detail below. High folate foods include black-eye beans, Brussels sprouts, beef and yeast extract, kale, spinach, granary bread, spring greens, broccoli, parsnips and chickpeas. Liver is also very high in folic acid, but also very high in vitamin A also. Overcooking of course destroys folate, as well as other B-vitamins.

http://en.wikipedia.org/wiki/Folate

A deficiency in Folate or its derivatives may result in elevated homocysteine levels, megaloblastic anaemia (THF required by bone marrow for RBC production), heart disease or DNA damage.

http://en.wikipedia.org/wiki/Megaloblastic_anemia Conversion of Folate into THF:

To be utilised in the body, folate undergoes a series of conversion steps, from its biologically inactive form to a biologically active form. Additional is capitalisation used for emphasis.

Protein Function and Amino Acid Conversion:

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General:

What is an amino acid? It is a molecule consisting of an amine group and a carboxlic acid group.

Phenylalanine is shown above an amino acid with an aromatic phenyl group (the carbon 'benzene' ring). Amino acids are the most primary molecular building blocks of complex proteins, in practical terms - without splitting them into individual carbon, nitrogen, hydrogen and oxygen atoms etc. In the digestive tract, proteins are broken down (hopefully) into their constituent amino acids with the action of stomach acid and digestive enzymes, and the actual conversion of amino acids from one form to another occurs in the cells of the body with the action of a variety of specialised enzymes. Both areas are of critical importance to ensure correct utilisation of amino acids in the body.

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Categories of Amino Acid:

There are broadly speaking three categories of Amino Acids. Those Amino Acids that are required by the body in order to function properly and that cannot be synthesised by the body (converted enzymatically from other amino acids or groups of compounds) at all or quickly enough and in sufficient quantities are classed as (Nutritionally) Essential Amino Acids. These include 'branch chain' amino acids, a.k.a. BCAAs, that have non-aromatic (aliphatic) side chains (marked with a '+' below). Those amino acids that can be synthesised by the body in sufficient quantities and quickly enough under normal circumstances, and are classed as Nonessential Amino Acids. Semi-Essential (or Conditionally Essential) Amino Acids are required from dietary sources under special circumstances.

Despite the names, it is of critical importance for Semi-Essential and Non-Essential Amino Acids to be made available (in the right quantities and at the right time) in the body for proper biochemical functioning to occur. Both Essential and Semi-Essential Amino Acids can be derived from nutritous dietary sources, but in special cases, either because of digestive problems or specific enzymatic conversion pathways being impeded, supplementation may be required of a special amino acid or acids from any of all of the three groups to alleviate a deficiency/imbalance.

Essential Amino Acids:

- Isoleucine+
- Leucine+
- Lysine
- Methionine
- Phenylalanine
- Taurine
- Threonine
- Tryptophan
- Valine+

Semi-Essential Amino Acids:

- Arginine*
- Histidine*

Non-Essential Amino Acids:

- Alanine
- Asparagine
- Aspartic Acid
- Cysteine*
- Cystine
- Glutamic Acid
- Glutamine*
- Glycine*
- Proline*
- Serine*
- Tyrosine*

The definitions above are those cited by Genova Diagnostics. The definitions of Semi-Essential and Non-Essential are not always fully agreed upon. Cysteine, taurine, tyrosine, histidine and arginine are regarded as Semi-Essential Amino Acids in children, because the metabolic pathways that synthesize these amino acids are not fully developed. Wikipedia classes those amino acids marked with a '*' as being Semi/Conditionally Essential.

http://en.wikipedia.org/wiki/Amino_acid

www.aminoacidpower.com/aboutAmino/Tour

http://jn.nutrition.org/cgi/content/full/130/7/1835S

http://jn.nutrition.org/cgi/content/full/134/6/1558S

Amino acids join together through joining the amino (nitrogen) group on one amino acid molecule with the carboxylic (acidic carbon) group of another amino acid molecule. This is known as an amide bond and is a form of polymerisation. This occurs through RNA or enzyme initiated activity in the body. Amino acids join in this manner to form short peptide chains or longer polypeptide chains. Polypeptides are also known as proteins.

Clearly there are many different types of amino acid, different in structure, number of carbon atoms, and configuration (isomers, single chain or branch chain (i.e. main chain and branch chain placement and length)). Optical isomers (mirror image molecules with the same number of atoms in them but which are not identical (e.g. a mirror reflection of you), can exist in two forms, 'D' or 'L'. The letter prefixes the amino acid name (e.g. L-Glutamine). 'L' describes the vast majority of amino acids found in proteins and sometimes the L nomenclature is dropped (considered superfluous). The exact structure of an amino acid determines its properties and characteristics, including its hydrophilic or lipophilic properties. Some amino acids and peptides are capable of crossing the blood brain barrier whereas other are not. This is why certain peptides (and 'nano-particles') in certain detoxification products and herbs are ablet o cross the blood brain barrier and provide effective chelation of heavy metals from the brain cells.

http://en.wikipedia.org/wiki/Blood_brain_barrier

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Proteins and Protein Structures:

As well as the huge variety of individual amino acids, there is also a huge variety of protein structures that can be created by them, a little like words that can be created out of letters in the alphabet. Amino acids then are the basic building block of life, and without their existence, no (terrestrial carbon-based) life forms could exist.

http://en.wikipedia.org/wiki/Amino_acid

There are number different types of protein in the body, and they are not just used for the making up cell membranes (e.g. to form muscle, skin and the organs), i.e. structural proteins. Cell membranes are made up of lipids as well as protein. This is why it is important that sufficient Essential Fatty Acids and the right ratios, and also quality sources of protein are consumed; and also why it is important to keep these cell membranes free of toxins.

Other uses for proteins in the body include the formation of enzymes (digestive, immune system, anti-inflammatory and detoxification enzymes), hormones (chemicals that allow one cell to communicate to another and control its metabolism), neurotransmitters (chemicals that allow a neuron (in the nervous system) to signal a cell or cells), antibodies, blood transport proteins, etc.

http://en.wikipedia.org/wiki/Enzyme

http://en.wikipedia.org/wiki/Hormones

http://en.wikipedia.org/wiki/Neurotransmitter

http://en.wikipedia.org/wiki/Neuron

Please see the Mitochondrial Dysfunction page for more information on the role of L-Carnitine in ATP transport and cellular energy production.

Quoting from Wikipedia regarding the functions of proteins:

http://en.wikipedia.org/wiki/Protein

'Proteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes. With the exception of certain types of RNA, most other biological molecules are relatively inert elements upon which proteins act....

The chief characteristic of proteins that allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by the tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific...

Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of the same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein-protein interactions also regulate enzymatic activity, control progression through the cell cycle, and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex signaling networks.

The best-known role of proteins in the cell is as enzymes, which catalyze chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism, as well as manipulating DNA in processes such as DNA replication, DNA repair, and transcription. Some enzymes act on other proteins to add or remove chemical groups in a process known as post-translational modification. About 4,000 reactions are known to be catalyzed by enzymes. The rate acceleration conferred by enzymatic catalysis is often enormous - as much as 1017-fold increase in rate over the uncatalyzed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme).

The molecules bound and acted upon by enzymes are called substrates. Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with the substrate, and an even smaller fraction - 3-4 residues on average - that are directly involved in catalysis. The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.

Many proteins are involved in the process of cell signaling and signal transduction. Some proteins, such as insulin, are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues. Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell.

Antibodies are protein components of adaptive immune system whose main function is to bind antigens, or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as plasma cells. Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.

Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin, which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom.

Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse. Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions.

Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins; for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that comprise the cytoskeleton, which allows the cell to maintain its shape and size. Collagen and elastin are critical components of connective tissue such as cartilage, and keratin is found in hard or filamentous structures such as hair, nails, feathers, hooves, and some animal shells.

Other proteins that serve structural functions are motor proteins such as myosin, kinesin, and dynein, which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and the sperm of many sexually reproducing multicellular organisms. They also generate the forces exerted by contracting muscles.'


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Amino Acid Conversion & Protein Formation Bottlenecks:

As has been illustrated above, the ability to form proteins is critical to the functioning of the body and life itself. Protein formation is often impaired in CFS cases. Protein formation is itself dependent on many factors, but most importantly, the supply of amino acids into the body. These are supplied by the digestive tract and digestive enzymes and stomach acid, which act to break down the plant and animal proteins in the food that we eat into amino acids, and hopefully allow sufficient quantities to be absorbed into the blood stream for polymerisation and conversion into specific amino acids and peptide chains for various functional proteins and structural in the body. Digestion then is the first step in protein and amino acid conversio.

A blockage or bottleneck in the ability to convert one type of amino acid to another can result in elevated levels of the precursor amino acid and very low levels of the converted amino acid. Elevated levels of the precursor amino acid may well have biochemical effects on the body, and indeed the low levels of the converted amino acid are also likely to have significant effects on a particular process or pathway in the body. Amino acids are converted from one form to another, and joined together to form specific peptides and polypeptides. If one type of amino acid is low, then all downstream amino acids and peptides that rely on this 'precursor' are going to suffer or rather be considerably compromised/slowed down in their synthesis with signficant and specific effects. Digestive impairment can lead to a 'Catch 22' situation (affecting enzyme production and metabolic signalling, which affects digestive capability etc.) unless we do something to reverse this cycle. Clearly this can create quite a complex picture. An example of one such problem is that of methylation and glutathione production, examined in the next section on this page.

The amino acids which are too high or too low can be determined by a variety of methods, either a blood test or a urine test (e.g. Amino Acid Profile). Please see the Identification page for more information. The importance of such tests should not be under-estimated. They may point to what nutritional elements (e.g. minerals or vitamins) are missing from the diet or have been too low for low long, resulting in a severe amino acid imbalance in the body, or which specific amino acids can perhaps be supplemented for a brief period to considerably assist in one's recovery. As discussed on the Digestion page, certain readily assimilable and high quality protein sources may also help in this regard.

Please see Mineral Deficiencies section for more information on digestive problems, nutrient malabsorption and their effect on amino acid utilisation.

Below are a number of amino acid case studies.

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Taurine:

Taurine, a.k.a. 2-aminoethanesulfonic acid is an organic acid which is synergistic with magnesium delivery to the body's cells. Taurine is an ion and pH buffer in the heart, muscles and central nervous system. It is also a major constituent of bile. It is also a powerful antioxidant and antitoxin, particularly important to the liver and immune system. Taurine is also classified as a 'semi-essential nutrient'. It is bio-synthesised from the amino acid Cysteine as an end product of Cysteine metabolism. It is not involved in protein formation but has a variety of biochemical functions in the body. As stated above, studies have shown that taurine levels in vegans are frequently significantly lower than in those eating meat and dairy products. Taurine also acts as a calming neurotransmitter, in a similar way to GABA, to balance the excitatory (excitotoxin) pathways of Aspartate and Glutamate.

http://en.wikipedia.org/wiki/Taurine

www.vitamins-supplements.org/amino-acids/taurine.php

'Taurine is a nonessential amino acid, which means that it is manufactured from other amino acids in the liver. Taurine is found mostly in meat and fish. Good sources of taurine include brewer's yeast [high in Glutamate], eggs and other dairy products, fish and red meat.'

Taurine is found in certain energy drinks (as an additive), which are otherwise quite bad for you, as they are highly acidic, and usually extremely high in caffeine.

If elevated Taurine levels are detected in the urine, there may be two possible causes, either an excess dietary intake or heavy supplementation; and/or urinary wasting of Taurine by the kidneys due to poor renal conservation. Urinary wasting can be secondary to a generally increased level of renal clearance or nephrotic syndromes (where the kidneys are damaged and leaking large amount of protein into the urine). Wasting of Taurine can also occur when the similarly-structured amino acid beta-alanine is elevated (e.g. bacterial dysbiosis) or is present in the kidney tubules. In cases of Molybdenum deficiency or sulphite oxidase enzyme impairment, elevated urine taurine can result as an emergency method of sulphur excretion.

Renal wasting of Taurine can be medically significant if it affects one of more of Taurine's various important functions, listed below.

Pathologies attributed to taurine deficiency in the cells include billiary insufficiency, fat malabsorption (steatorrhea), cardiac arrhythmia, congestive heart failure, poor vision, retinal degeneration, granulomatous disorder of neutrophils, immune system dysfunction, enhanced inflammatory response to xenobiotics (toxins of foreign origin), convulsions and also seizures.

Taurine excess in the tissues is an uncommon condition (hypertrauinuria with hypertaurinemia) is usually a result of insufficient sulphite oxidase enzyme activity, perhaps on account of molybdenum deficiency. It may also be a result of increased levels of beta-alanine in the urine (renal clearance). Increased levels of urinary sulphites and decreased levels of sulphates are observed in the urine. If molybdenum levels are too low, then uric acid levels are also reduced, xanthine levels are elevated and aldehyde detoxification is impaired (i.e. aldehyde intolerance).

Source: Genova Diagnostics Optimum Nutrition Evaluation. Please see the Tests page for more information.

Low tissue taurine levels and low Magnesium tissue levels are often observed in CFS, ME and Fibromyalgia patients. Many good magnesium supplements contain Taurine (such as Ultra Muscleze). L-Methionine is a precursor to Taurine which may also be taken to assist in nutrient assimilation. However, no amino acid supplementation should be undertaken without guidance from a qualified practitioner and a urine test (amino acid analysis profile).

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Cysteine and Cystine:

http://en.wikipedia.org/wiki/Cystine

Cysteine is the chemically reduced and biologically active form of Cystine. Cysteine is a precursor to Glutathione, Glutathione containing Cysteine. Cysteine is considered to be the limiting amino acid for the formation of Glutathione, which is required for organ and tissue detoxification and as a major endogenous antioxidant. Sulphur-based detoxification via sulphation (sulfation in the USA!) also starts with Cysteine as the primary source of sulphur.

Cysteine is produced from the amino acid Methionine during a process known as Methylation, which converts Methionine into Homocysteine, into Cysteine. Please see the Homocysteine section below for more information about Methionine and Glutatione, and also the Inefficient Liver Function page.

Cysteine and Cystine are derived from dietary protein sources:

http://en.wikipedia.org/wiki/Cysteine#Dietary_sources

'Cysteine is found in most high-protein foods, including:
- Animal sources: pork, sausage meat, chicken, turkey, duck, luncheon meat, eggs, milk, whey protein, ricotta, cottage cheese, yogurt
- Vegan sources: red peppers, garlic, onions, broccoli, brussels sprouts, oats, granola, wheat germ'

Cysteine is also formed in the cells from the essential amino acid Methionine, with the cofactor Vitamin B6. Cysteine deficiency may be secondary to dietary protein insufficiency, gastrointestinal dysfunctions, methionine insufficiency, impaired methionine metabolism/conversion, urinary wasting of Cystine (Cystinuria), and urinary wasting of Taurine. Taurine is a metabolite of Cysteine, and both are created by the body from Methionine. Cysteine deficiency can lead to a reduced ability to detoxify (i.e. a Glutathione deficiency), chemical or xenobiotic (external chemical) intolerances, oxidative stress and increased inflammatory responses. Low cysteine levels or a Cysteine to Cystine ratio of less than 0.75 is synonymous with oxidative stress.

Sufficient Cysteine levels are important to maintain liver function, protect the liver, maintain glutathione production and to help prevent undue oxidative stress.

http://en.wikipedia.org/wiki/Cystine

Cystine is the oxidised or dimer form of Cysteine. It is essentially two Cysteine molecules linked together with a Sulphur-Sulphur (S-S) bond. In the form of Cysteine, as mentioned above, it is a protein amino acid and a key component of Glutathione, CoEnzyme A, various enzymes and also insulin. Cystine is found in meat, eggs, milk products and whole grains. Cystine is the extracellular form of Cysteine. Cystine deficiency is synonymous with protein malnutrition, gastrointestinal dysfunctions (absorption/digestion problems) or the impaired metabolism of Methionine.

Source: Genova Diagnostics Optimum Nutrition Evaluation. Please see the Tests page for more information.

www.vitaminstuff.com/amino-acid-cystine.html

'Cysteine is more easily absorbed by the body than cystine, so most supplements contain cysteine rather than cystine [e.g. L-Cysteine, N-Acetyl-Cysteine (NAC)]. In addition, too much cystine in the body can cause cystinosis, a rare disease that can cause cystine crystals to form in the body and produce bladder or kidney stones. This side effect has not been associated with cysteine; however...cysteine is unstable, and is often converted to cystine in the body. To avoid the conversion of cysteine to potentially harmful amounts of cystine, it is advised that you take vitamin C supplements or consume citrus fruits along with cysteine supplements. Cystine cannot be used by the body without adequate amounts of vitamin B6, vitamin B12, and folic acid, so you'll want to make sure you get the right amount of these supplements as well.'

www.ithyroid.com/goitrogens.htm

Copper and Iron play an important role in thyroid functioning, and excessive levels of dietary sulphur (e.g. Cysteine or MSM) may inhibit the uptake of Copper and Iron, potentially causing hypothyroidism.

A document 'Treatment Options for Mercury/Metal Toxicity in Autism and Related Developmental Disabilities: Consensus Position Paper February 2005' by the Autism Research Institute, claims that both Cysteine and N-Acetyl-L-Cysteine (NAC) can bind with mercury and carry it across to other tissues, allegedly toxifying the body further (although clearly this depends on where the Mercury was and where it is going to!); and also that these amino acids are readily consumed by various yeast species and taking too much can result in the exacerbation of yeast infections. Clearly Cysteine is required by the body and a dietary intake of Cysteine within the normal range is a important to ensure sufficient Glutathione production for detoxification purposes. The document discusses Cysteine and NAC on pages 19-20, and can be read by clicking on the link below.

http://www.autism.com/pdf/providers/heavymetals.pdf

Please see the Endocrine disrupting foods section on the Digestive Disorders page.

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Glutamine and Glutamic Acid

Glutamic acid is a non-essential amino acid that has an excitatory function of the nervous system. Glutamic acid is the acidic form of the salt Glutamate. Too much dietary intake however can result in neurological damage and neurotransmitter imbalance. Please see the Protein Food Additives section below for more information about Glutamate and Excitotoxins.

Isolated glutamic aciduria is consistent with the following conditions:

Provided no other conditions are present, Glutamic acid levels should normalise after discontinuing the first two items above (i.e. eliminating most or all dietary sources of Glutamic acid). The third and fourth conditions are usually best corrected with a low purine diet. Purine metabolism disorders are not very common, and differential diagnosis is difficult. In metabolic or renal acidosis, glutaminase in the kidneys forms glutamic acid and ammonia which becomes basic ammonium hydroxide (NH4OH). This is the body's normal pH balancing mechanism for balancing acidosis. Acidoses can feature an increased serum anion gap (ketoacidoses of diabetes or alcoholism or lactic acidoses of respiratory insufficiency, chemical toxicity, circulatory problems etc.) or may be hyperchloremic with normal anion gap (renal tubular acidosis, hypoaldosteronism, alkali-loss diarrhea) etc.

In a urine sample, the glutamine/glutamate ratio can indicate specimen decay. When aged or improperly preserved, urine glutamine decays to glutaic acid and ammonia. In metabolic acidosis some glutamine is transformed into glutamic acid and ammonium ion as a pH balancing mechanism. This may contribute to high ammonia levels in the blood or urine. As mentioned above, high glutamic acid levels occur in gout also. Thus, low glutamine/glutamate ratio may reflect decay, too high a dietary glutamate intake or it may be of metabolic origin. High glutamine/glutamate ratio is metabolic and does not reflect on specimen decay or representativeness.

An elevated ammonia urine concentration usually indicates overall decay of amino acids (i.e. is time dependent). An exception would be elevated ammonia concentration with hyperammonemia of metabolic or bacterial origin. A very low urine ammonia concentration suggests low urine nitrogen levels, which may occur in protein-deficient diets; blood amino acid levels may well be normal or slightly sub-normal.

Source: Genova Diagnostics Optimum Nutrition Evaluation. Please see the Tests page for more information.

Glutamine is used to produce both Glutamic Acid (Glutamate - the upregulating amino acid) and also GABA (down-regulating amino acid). Please see the Hormone and Neurotransmitter page for more information about GABA and Glutamate.

http://orthosz.blogspot.com/2006/12/glutamine-and-gaba.html

Glutamine is also a major building block of skeletal muscles, which are a major concentration of Glutamine in the body. Muscle injury recovery can be assisted by Glutamine supplementation. Glutamine is also a major constituent of the intestinal mucosal cells and Glutamine supplementation can help inflamed or damaged intestinal walls (i.e. Leaky Gut Syndrome). Glutamine also acts as a carbon donor, supporting protein synthesis and the rate of glycogen production.

www.lef.org/magazine/mag99/sep99-report3.html

"The synthesis of glutamine protects the body, and the brain in particular, from ammonia toxicity. In fact, the synthesis of glutamine from glutamate is the key pathway for detoxifying ammonia. Excess ammonia is a crucial factor in the development of neurodegenerative diseases, since ammonia interferes with the oxidative metabolism of neurons and thus reduces the production of ATP, our "energy molecule." In addition, ammonia gives rise to very harmful nitrogen-based free radicals."

"In the brain, glutamine is a substrate for the production of both excitatory and inhibitory neurotransmitters (glutamate and gamma-aminobutyric acid, popularly known as GABA). Glutamine is also an important source of energy for the nervous system. If the brain is not receiving enough glucose, it compensates by increasing glutamine metabolism for energy-hence the popular perception of glutamine as "brain food" and its use as a pick-me-up. Glutamine users often report more energy, less fatigue and better mood."

"Glutamine also plays a part in maintaining proper blood glucose levels and the right pH range. The body has an exquisite mechanism for maintaining pH homeostasis. If the pH of the blood is too acidic, more glutamine is directed to the kidneys, where a certain type of glutamine results in the release of bicarbonate ions to correct acidosis. If the pH is too alkaline, more glutamine is sent to the liver, where a different kind of metabolism releases hydrogen ions to correct alkalosis."

"And there is still more. Due to its dependence on sodium transport, glutamine is one of the amino acids that control the volume of water in the cells, and the osmotic pressure (osmoregulation) in various tissues. Glutamine also plays a vital part in the control of blood sugar. It helps prevent hypoglycemia , since it is easily converted to glucose when blood sugar is low. In addition, glutamine regulates the expression of certain genes, including those that govern certain protective enzymes, and helps regulate the biosynthesis of DNA and RNA. Recently it has been discovered that glutamine is important for the cardiovascular system as well."

"The glutamine cycle in the brain is simple and elegant. Glutamine readily crosses the blood-brain barrier. Neurons take up glutamine and convert it to glutamate or GABA (through the additional step of decarboxylating the glutamate). Some glutamate is used for energy, some for synthesis of glutathione and niacin, some as neurotransmitter. After either glutamate or GABA are released into the synaptic junction, the supportive cells called glia, with their high supply of glutamine synthase, take up the glutamate or GABA and resynthesize glutamine, detoxifying ammonia in the process. The glutamate that is not converted to glutamine is used by the glia as a source of energy, and also to produce energy nutrients alanine and alpha-ketoglutarate, which are then released to the neurons."


http://en.wikipedia.org/wiki/Glutamine#Dietary_sources

'Dietary sources of L-glutamine include beef, chicken, fish, eggs, milk, dairy products, wheat, cabbage, beets, beans, spinach, and parsley. Small amounts of free L-glutamine are also found in vegetable juices and fermented foods, such as miso [also high in Glutamate].'

According to Genova Diagnostics:

Pyroglutamic Acid (5-oxoproline) primariliy arises as a byproduct of the 'gamma-glutamyl cycle' which splits reduced glutathione (GSH) into cysteinylglycine and a gamma-glutamyl moiety. The gamma-glutamyl part attaches to another amino acid or short-chain peptide, or combines with an essential mineral element for transport across a membrane or into a cell. Uptake of such nutrients from the small intestine is primarily dependent on this process. The enzyme gamma-glutamylcyclotransferase completes the transport role by splitting off the constituent parts carried through and changing the gamma-glutamyl parrt into pyroglutamic acid. A deficiency in pyroglutamic acid may result from a deficiency of reduced glutathione (GSH), toxicity (causing a depletion of GSH), oxidative stress limiting the amount of the reduced form of glutathione (i.e. oxidising it), cellular magnesium deficiency which can limit the rate of endogenous GSH formation, and also a deficiency of Cysteine (as stated above, which is the bottle-neck in endogenous GSH formation). Symptoms of Pyroglutamic Acid deficiency include nutrient malabsorption, oxidative stress and/or toxicity.

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Asparagine:

http://en.wikipedia.org/wiki/Asparagine

Asparagine has various dietary sources, including vegetable protein foods such as soy, peanuts and other legumes. It can also be formed endogenously in the body from glutamine and aspartic acid. Endogenous formation of asparagine is Magnesium dependent and requires an energy-coupled ATP step to be manufactured by the body. Low urinary asparagine levels can be a result of poor renal clearance (i.e. inefficient kidney function), in which case one would expect 24 hour creatinine urine levels to be low and blood/tissue asparagine levels to be elevated (as it is not being cleared by the kidneys). Asparagine deficiency may be a result of a low protein diet in general, from a diet deficient in vegetable protein, from gastrointestinal dysfunction and poor absorption and uptake of amino acids, or it may be a result of a magnesium deficiency or dysfunction. Normal or elevated levels of aspartic acid and glutamine in conjunction with low asparagine levels are consistent with Magnesium dysfunction. Low asparagine levels may limit leukocyte numbers and function, and may thus contribute to immune system dysfunction.

Source: Genova Diagnostics Optimum Nutrition Evaluation. Please see the Tests page for more information.

A diet supplying 55g of protein provides approximately 4g of Asparagine, according to J.R. Carlson Laboratories (amino acid suppliers) - assuming protein digestion and absorption is functioning correctly.

One's recommended weight and daily protein intake can be calculated at the web site below.

www.indoorclimbing.com/Protein_Requirement.html

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Beta-alanine:

Beta-alanine is often elevated when the dietary peptides anserine and carnosine are elevated because they contain beta-alanine. Beta-alanine is also a metabolite of the pyrimidine bases cytosine and uracil. Catabolism (breakdown) of damaged or diseased bodily tissue, tumors and malignancy feature increased production and urinary disposal of beta-alanine. Besides elevated anserine or carnosine and accelerated catabolism of unwanted bodily tissue, the next most likely source of beta-alanine in urine is imbalanced gut flora. The normal gut flora produce some beta-alanine, which they make pantothenic acid (vitamin B5) from. However, elevated levels of staphylococcus or streptococcus, use of antibiotics, and the breakdown of yeast or fungi in the body can cause an increase in urinary beta-alanine levels. Continuously elevated beta-alanine can be detrimental by impairing renal conservation of taurine.

Source: Genova Diagnostics Optimum Nutrition Evaluation. Please see the Tests page for more information.

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Sarcosine:

Sarcosine, or N-methylglycine, is an intermediate of the choline-to-serine catabolism (breakdown) sequence, and the N-methyl derivative of glycine. http://en.wikipedia.org/wiki/Sarcosine

'Sarcosine is ubiquitous in biological materials and is present in such foods as egg yolks, turkey, ham, vegetables, legumes, etc. Sarcosine is formed from dietary intake of choline and from the metabolism of methionine, and is rapidly degraded to glycine, which, in addition to its importance as a constituent of protein, plays a significant role in various physiological processes as a prime metabolic source of components of living cells such as glutathione, creatine, purines and serine.'

It is formed by the oxidative demethylation (i.e. removal of a methyl CH3 group) of dimethylglycine (DMG) and it is then catabolised by further demethylation. Elevated sarcosine levels (if observed) in the urine suggest three possibilities:

Unpublished clinical observations associate some cases of acquired, mild sarcosinuria with past exposures to organic chemical solvents and petrochemicals. At such levels sarcosine is not known to become toxic. However, folic acid supplementation is recommended whenver sarcosine is elevated.

Source: Genova Diagnostics Optimum Nutrition Evaluation. Please see the Tests page for more information.

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Amino Acid Supplementation - General Principles:

Please note that amino acids can be taken in their acid format, or as amino acid salts of a nutritional metal. For example, if one wishes to take 'butyrate', then one can either take butyric acid or for example calcium and magnesium butyrate. If one takes a chelated mineral supplement (i.e. an amino acid salt), for example, magnesium citrate, then this may result in a large amounts of citrate being consumed. Intake of disproportionately large amounts of certain amino acids may have no ill effect on the amino acid balance and conversion processes that take place in the body. Others however may put the body into imbalance with respect to certain amino acids, and their precursors or the amino acids they are normally converted to. An amino acid analysis should highlight any problems that would be occurring in the body.

As discussed above, one can identify which amino acids are deficient in one's blood or urine, and then supplement these with the guidance of one's practitioner, to partially redress the balance and assist in the general process of increasing levels of downstream peptides, polypeptides, enzymes and hormones, which will (together with other therapies and nutrition sources) in turn assist in amino acid conversion, gradually remedying the problem. Clearly one cannot just do this cannot just do this on a whim, interpreting one's own amino acid test results and deciding for oneself what one should take, i.e. anything that seems low. As with balancing hormones, amino acids need to be taken in the right ratios and amounts to be effective. One needs to determine which aminos are in the normal range, which are too low, which are too high, and why; and what are the relative ratios of certain related amino acids. As some amino acids are precursors for others, then one may wish to target a specific amino acid rather than an entire group of amino acids. Sometimes the body may best benefit from the end product rather than the precursor. One may also want to consider the best form of the amino acid to take, that the body most requires and can utilise, e.g. choosing between Acetyl-L-Carnitine vs Carnitine Fumarate or other forms. This can be determined using muscle testing for example. Amino acid levels can tell one a great deal about potential hormonal problems, potential B-vitamin levels or even immune system issues like candida.

Urine amino acid levels are usually representative of the blood levels and reflect dietary uptake and metabolism, as well as excretion of these amino acids. However, a number of factors must be taken into consideration, as the urine levels may not necessarily correspond directly to the blood or tissue levels. For example, abnormal renal clearance, loss of urine during the collection period, decay or spoilage of the urine sample, and the presence of blood in the urine could cause the sample to be unrepresentative. However, the possibility of such problems can be judged from analytical measurements (metabolic markers for urine representativeness.)

One particular product that should be mentioned is called Custom Amino Acids by Dr David Gersten, which is as its name suggests, a custom blend of amino acid that a particular patient requires, in the relative ratios and amounts that are required, and is tailor/custom made according to the patients amino acid profile test results. One can emulate this oneself by buying a variety of different aminos and tweaking the amount of each one oneself, and/or very careful dietary planning, but this is an extremely convenient and also proven method and approach. The blend I presume is based on Montiff amino acid powders that Dr Gersten uses.

www.aminoacidpower.com/consult/supplementSchedule

Metametrix in the USA also offers a Bloodspot Amino Acid Assay test, which is available for 11 or 20 amino acids, and is a blood test using a blood spot sample taken from the finger. This is described on the Identification page. The 11 test includes: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Taurine, Threonine, Tryptophan and Valine. A 30 day amino acid powder supplementation recommendation is also provided with the test results, containing relative proportions and amounts of a variety of amino acids, amino precursors and B-vitamins, for a suitable pharmacist or practitioner to make up for you. Click here for more information about the blood spot, blood plasma and urine tests for amino acid analysis.

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Homocysteine Metabolism, Methylation, Transsulphuration & Glutathione Production:
 
What is methylation?

Methylation is the process of adding a methyl group (an extra carbon atom with three hydrogen atoms) to an amino acid to synthesize new, larger amino acids that the body requires to function properly. Methylation occurs in homocysteine metabolism. In a healthy body, methylation occurs over a billion times a second. Methylation is important in managing our DNA, converting amino acids to the required forms, producing adrenal neurotransmitters, red blood cells, the mitochondrial cofactors Coenzyme Q10 and L-Carnitine, and also in synthesising Glutathione.

The donation of methyl groups (CH3) affects many metabolic processes, as mentioned above, including brain chemistry (i.e. neurotransmitter production, e.g. Catecholamines or stress hormones), phosphatidyl choline production (a key nutrient in brain composition and cellular membranes - prone to free radical damage), mitochondrial function (i.e. creatine production) and DNA metabolism (methylation of DNA). Creatine for example helps to recycle ADP back to ATP. Demethylation of DNA is considered to be a contributary factor in the ageing process. If methylation is poor, then the production of these compounds may be impaired, with serious knock-on effects on the body.

Dr Sarah Myhill summarises some of the important functions of methylation in the article below.

www.drmyhill.co.uk/article.cfm?id=401

Methylation is essentially a type of Alkylation. Alkylation is the donating of a carbon/hydrogen group from one molecule to another. This is usually a methyl group (CH3), but in the generic sense could also be the donation an an Ethyl group (C2H5) etc. However, with regards to human biochemistry, we are concerned with methyl group donation only.

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What role do Methionine and Homocysteine play in Transsulphuration and Glutathione production?

Methionine is a sulphur-containing alpha-amino acid regularly consumed in the diet, and is particularly rich in food sources like fish.

http://en.wikipedia.org/wiki/Methionine

'As an essential amino acid, methionine is not synthesized in humans, hence we must ingest methionine or methionine-containing proteins. In plants and microorganisms, methionine is synthesized via a pathway that uses both aspartic acid and cysteine.'

When methionine-rich foods (e.g. fish) are consumed, the methionine is absorbed into the bloodstream and into cells, where enzymes convert it via a series of intermediate amino acids to Homocysteine. One of these intermediate steps is S-adenosyl methionine (SAM) which is a useful natural antidepressant, combats arthritis and is excellent at lowering homocysteine levels. Homocysteine is very detrimental to health at high levels and the body converts some of the homocysteine to cysteine, which is the building block for a variety of essential compounds in the body including Glutathione. As SAM levels increase, the body methylates Homocysteine to produce Glutathione. Glutathione is the body's greatest anti-ageing agent which is also used in detoxification. The body then converts any significant excesss of Homocysteine back to Methionine again by methylation So whilst Homocysteine is undesirable, it is required on demand and in sufficient quantities (but no more) to produce many of the body's compounds and hormones.

A diet supplying 55g of protein provides approximately 0.75g of Methionine, according to J.R. Carlson Laboratories (amino acid suppliers) - assuming protein digestion and absorption is functioning correctly.

One's recommended weight and daily protein intake can be calculated at the web site below.

www.indoorclimbing.com/Protein_Requirement.html

Cysteine and Glutathione play valuable roles in the areas of joint strength (production of glucosamine and chondroitin sulphates etc.) and also brain function (Cysteine and its derivatives are natural antidepressants). Cysteine also plays a valuable role in Taurine production, which is required for Magnesium transport. And of course critically, the transulphuration pathway (of GSH production) plays a valuable role in free radical management and liver function.

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Conversion of Methionine to Homocysteine:

To understand the importance of the above B-vitamins with regards to methylation, it is important to understand how homocysteine metabolism works.

Let us first examine the process of enzymatic synthesis of Homocysteine from Methionine. This occurs in three steps:

(1) Methionine is first combined with ATP (Adenosine Triphosphate) by the action of the enzyme Methionine AdenosylTransferase (MAT) to produce S-AdenosylMethionine (SAM).

(2) SAM in the presence of a Methyltransferase (MTase) enzyme then donates a methyl group (CH3 - i.e. one carbon atom and 3 hydrogen atoms) to another recipient molecule 'X' (i.e. methylation), leaving S-AdenosylHomocysteine (SAH) as a byproduct. Molecule X could include DNA, RNA, proteins, membrane phospholipids and neurotransmitters etc. Methyltransferase enzmyes are dedicated to the exact recipient molecule, so their presence can control exactly which type of molecule SAM donates its methyl group to.

(3) SAH is then combined with a water molecule (H2O), whereby Adenosine is cleaved off, by the action of the SAH Hydrolase (SAHH) enzyme, leaving Homocysteine as a byproduct.

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The Function of S-AdenosylMethionine (SAM-e):

S-Adenosyl Methionine, also known as S-Adenosylmethionine, SAM, SAMe or SAM-e, is an amino acid derivative that is an intermediate co-substrate involved in methyl group transfers.

http://en.wikipedia.org/wiki/S-adenosylmethionine

It is formed by reacting ATP with methionine, and is found in all living cells. It is thus often referred to as 'activated methionine'. In clinical trials involving thousands of patients it has been shown to provide proven benefits to brain and joint function. Arguably it may be more efficient to supplement with SAM-e rather than methionine, as converting methionine to SAM-e uses up ATP, and if a patient is low on ATP availability, it makes sense to move slightly further up the chain in supplemental terms.

Most of the benefits of SAM-e are as its role as an intermediate in the production of Cysteine and Glutathione. There are some specific benefits to SAM-e however, which are mentioned below.

Jarrow Formulas argue that supplementation with methionine can result in an elevation of Homocysteine and little cellular SAM-e elevation, although I cannot personally see a good reason why this should be, as they are both precursors to Homocysteine. Supplementation with SAM-e can potentially contribute to elevated toxic Homocysteine levels if the requisite vitamins (especially Methyl-B12 and 5-MTHF (Active Folate) that form part of the enzyme MTR required to break down Homocysteine back to Methionine are deficient. Please see the Re-Conversion of Homocysteine back into Methionine section below.

According to Wikipedia, other potential side effects of SAM-e include insomnia if taken too late in the evening, lack of appetite, diarrhea or constipation, dry mouth, sweating, rashes and anxiety (presumably down to increased Catecholamine production). As SAM-e is a weak DNA-methylating agent, it may perhaps also act as a weak carcinogen. Some also theorise it could potentially contribute to serotonin syndrome, whichin the extreme can be fatal. However, methylation is the process that converts serotonin into melatonin and other compounds, so I cannot see how too much SAM-e can contribute to too much Serotonin. This would presumably be a function of too much Trypophan or 5-HTP, the precursors (raw materials) to serotonin. Clearly the correct amino acid balance and intake is recommended, and too much of any one amino acid is not a good thing.

Myself and others have experienced mild headaches or allergic reactions when taking SAM-e, which may be on account of too high dosages or artificially created imbalances through supplementation. It is always best to have an amino acid profile performed prior to considering amino acid supplementation.

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Conversion of Homocysteine into Cysteine:

Homocysteine is a necessary intermediate product in the synthesis of Cysteine (steps 5 and 6), and the conversion of Homocysteine to Cysteine through Transsulphuration (the swapping of one Sulphur molecule for another) is described below:

(5) Homocysteine is combined with the amino acid Serine by the action of the enzyme Cystathionine Beta Synthase (CBS), in the presence of Pyridoxal-5-Phosphate (P5P, or acive B6), to produce Cystathionine.

(6) Cystathionine is the converted to Cysteine and alpha-ketobutyrate using the enzyme Cystathionase, in the presence of Pyridoxal-5-Phosphate (P5P, or acive B6).

http://en.wikipedia.org/wiki/Methionine

'Both cystathionine-beta-synthase [CBS] and cystathionine-gamma-lyase [a.k.a. cystathionase] require Pyridoxyl-5-phosphate as a cofactor'

http://en.wikipedia.org/wiki/Cystathionine_beta-synthase

http://en.wikipedia.org/wiki/Cystathionine-gamma-lyase

'Cystathionine gamma-lyase (or cystathionase) is an enzyme which breaks down cystathionine into cysteine and alpha-ketobutyrate. Pyridoxal-5-phosphate is a prosthetic group of this enzyme.'

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Function of Cysteine:

Cysteine is used in the body to produce a variety of vital sulphur containing peptides, amino acids, neurotransmitters/hormones, mitochondrial cofactors and phospholipids in the body (sulphur metabolism - the transsulpheration pathway), via a process of methylation and transsulphuration, including:

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Re-Conversion/Re-Methylation of Homocysteine back into Methionine:

(4) Excess homocysteine is converted back/remethylated into methionine. This occurs with the action of the addition of a methyl group from 5-Methyl-THF (5-MTHF, or the vitamin Active Folate) to the Homocysteine molecule, in the presence of the enzyme Methionine Synthase (MS) and Methyl-B12, in combination with the enzyme SAH Hydrolase (SAHH), to produce Methionine and THF (a folate intermediate).

(Cobalamin (B12)-dependent) Methionine Synthase (MS) is also known as Homocysteine Methyltransferase (MTR) or 5-MethylTetraHydroFolate-Homocysteine MethylTransferase, in mammals (e.g. humans). MTR is a gene and an enzyme.

MTR contains the cofactor - methylcobalamin (MeB12, Vitamin B12 in the form Methyl-B12) and uses the substrates N5-methyl-tetrahydrofolate (N5-methyl-THF, i.e. 5-MTHF (Active Folic Acid/Vitamin B9)) and homocysteine.

http://en.wikipedia.org/wiki/5-Methyltetrahydrofolate-homocysteine_methyltransferase

'The enzyme [MTR] works in two steps in a ping-pong reaction. First, methylcobalamin is formed by a methyl group transfer from N5-mTHF with formation of MeB12 and tetrahydrofolate (THF). In the second step, MeB12 transfers this methyl group to (homocysteine), regenerating the cofactor cobalamin and releasing the product methionine.'

http://en.wikipedia.org/wiki/Methionine

'...homocysteine methyltransferase [MTR] requires Vitamin B12 as a cofactor.'

There is also a second pathway or method of reconverting/remethylating Homocysteine back to Methionine:

'[Homocysteine]...can also be remethylated using Glycine Betaine (NNN-TriMethylGlycine) to Methionine via the enzyme Betaine-Homocysteine MethylTransferase (E.C.2.1.1.5, BHMT). BHMT makes up to 1.5% of all the soluble protein of the liver, and recent evidence suggests that it may have a greater influence on methionine and homocysteine homeostasis than methionine synthase (MS or MTR).'

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The requirements for Folate, P5P and Methyl B12:

Sufficient availability of folates (e.g. 5-MTHF), B12 and also P5P are clearly very important in the regulation of homocysteine in the body, Glutathione production and its conversion back to methionine. Vitamin 12 helps to protect nerve tissue and brain cells, and also helps to promote better sleep. It also helps to protect the eye function against toxicity caused by excess glutamate.

http://en.wikipedia.org/wiki/Methionine_synthase

'Deficiency in MTR function [i.e. ability to remethylate homocysteine back to methionine] may be due to genetic mutations, reduced levels of its cobalamin cofactor (vitamin B12), or decreased levels of the enzyme methionine synthase reductase (required for the sustained activity of MTR).'

Clearly a shortage of either the raw materials, e.g. Methionine, or a deficiency in the requisite enzymes or B vitamin cofactors can create a bottleneck in the methylation/transsulphuration process and prevent sufficient Glutathione production. Ironically, many of the enzymes involved in the whole methylation and transsulphuration pathway are actually created through methylation, so if methylation is impaired for any reason, the relevant enzymes that are involved in these processes will also be reduced, creating a vicious cycle.

Please see the diagram below for a summary of the vitamin/enzyme interactions (reproduced (modified/corrected) from very useful AutismCoach.com web site).



http://www.autismcoach.com/Glutathione%20Research.htm

A good overview of the nature of methylation blockage can found be on the research pages of PhoenixCFS, entitled 'Glutathione Depletion-Methylation Cycle Block: A Hypothesis For the Pathogenesis of Chronic Fatigue Syndrome' by Richard A. Van Konynenburg Ph.D. CFS research pioneer Dr Paul Cheney initially based many of his theories on Konynenburg's papers (and also Pall's), although they have to a large degree been working in parallel. It is worth reviewing the research pages on Phoenix-cfs.org in general also on this subject, cross referencing the Liver Function section on the Toxicity page on MedicalInsider also.

http://phoenix-cfs.org/GSHMethylationVanKonynenburg.htm

'The methylation cycle (also called the methionine cycle) is a major part of the biochemistry of sulfur and of methyl (CH3) groups in the body. It is also tightly linked to folate metabolism and is one of the two biochemical processes in the human body that require vitamin B12 (the other being the methylmalonate pathway, which enables use of certain amino acids to provide energy to the cells). This cycle supplies methyl groups for a large number of methylation reactions, including those that methylate (and thus silence) DNA, and those involved in the synthesis of a wide variety of substances, including creatine, choline, carnitine, coenzyme Q-10, melatonin, and myelin basic protein. Methylation is also used to metabolize the catecholamines dopamine, norepinephrine and epinephrine, to inactivate histamine, and to methylate phospholipids, promoting transmission of signals through membranes.'

Additional articles by or about Konynenburg can be found below.

http://phoenix-cfs.org/GluAACFS04.htm

http://phoenix-cfs.org/GSHMethylDeplTheoryJuly07.htm

http://phoenix-cfs.org/GSHMethylTrtPlanJuly07.htm

Dr Myhill's web site also cites research and ideas of Rich Van Konynenburg on methylation and suitable treatment.

www.drmyhill.co.uk/article.cfm?id=401

An article 'The Aetiology of ME : A personal hypothesis by Rich Van Konynenburg' can be found at the link below.

www.meactionuk.org.uk/hypothesis.html

Anyone with a low Glutathione production and methylation problems should be targeting these B Vitamins, and looking to test for their amino acid levels too, perhaps with an Amino Acid Profile urine test, to determine which amino acids should be supplemented, if any. In general terms, additional Methionine or SAM-e may be supplemented to help with methylation, if sufficient 5-MTHF and B12 is present; and Cysteine, NAC, Glutathione and/or P5P can be supplemented to address low Glutathione production, but in reality one should consider the entire pathway and look at trying to get it working, rather than bypassing a bottleneck and not fixing it, as there will be many knock on effects in the body if the initial methylation pathway is not working.

One should also consider the downstream effects of poor methylation capability, which includes low phospholipid production and brain chemistry (neurotransmitter) imbalances. Excessive free radical damage caused to the body's cell membranes (largely composed of phospholipids) by low Glutathione and SOD levels, and also from poor liver function (excessive free radicals circulating) will require a large intake/production of phosphatidyl choline in order to repair these cell membranes, and most importantly, mitochondrial membranes, to restore proper mitochondrial function. Neurotransmitter imbalances frequently require supplementation with many of the same B vitamins as described above, but also one may want to look into potentially taking the Serotonin/Melatonin precursor 5-HTP, and perhaps even Melatonin; and examining nutritional ways to stimulate neurotransmitter production.

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B-Vitamin Deficiencies and the results of high Homocysteine / low Glutathione levels:

Chronic deficiencies in the above B-vitamins (which affects many sufferers of CFS or related conditions) often results in the inability to methylate properly resulting in dangerously high Homocysteine levels and too low Glutathione levels. There are however other causes or contributary factors in high Homocysteine levels, for example, smoking, recreational drug use, chronic tobacco use, high alcohol consumption, reaching post-menopause, older age, post-heart attack or stroke, excessive niacin consumption (B3) and kidney failure. This is why people in old age and pregnant women (who have a higher demand for methylation) are recomended to take folic acid.

http://phoenix-cfs.org/GSHMethylTrtKonynenburg.htm

A low glutathione level has been linked to an increased risk of death from all common causes. High levels of homocysteine in the human body increase the risk of cardiovascular disease (i.e. strokes and heart attacks - on accont of raised levels of free radicals and increased build up of atherosclerotic plaque), pregnancy complications, the onset of Dementia and Alzheimer's Disease, Diabetes and Osteoporosis.

www.ncbi.nlm.nih.gov/pubmed/16510043

www.quackwatch.org/03HealthPromotion/homocysteine.html

www.drmyhill.co.uk/article.cfm?id=324

Some people ask whether one can die of CFS. Well, the answer is indirectly, yes. CFS often puts patients into the 'high risk' category of cardiovascular disease, and whilst it may not be a factor in the short term, if untreated, may well come into play in the long term. In addition, many of the factors that affect CFS patients are common to cancer patients, although I am not going to make any statement or direct connection between the development of cancer and CFS pre-disposing factors. Suicide rates are also much higher in CFS sufferers and those suffering from related conditions than in the rest of the population. Perhaps if these poor victims were properly informed about their conditions and sensible treatments by the medical authorities and media, then these (often assisted) suicides would not occur. In short, the key to a long healthy life is keep the homocysteine level down and the glutathione level up (in other words, to ensure that the body has sufficient B-vitamins and can methylate effectively).

The following web sites contain a basic overview of homocysteine metabolism and potential health implications.

www.gethsmart.com

www.lifeextensionvitamins.com/homred.html

www.homocysteine.net

There are other potential causative factors in CFS towards heart disease besides high homocysteine levels, low glutathione levels, oxidative stress and fatty acid imbalances. Heart insufficiency and impaired cardiac function are also a likely factor, and this is explored in more detail on the Heart Insufficiency page.

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Betaine as a homocysteine regulator and methylator:

Betaine, also known as trimethylglycine (TMG), is derived from sugar beet. Betaine has many commercial uses for example as a homocysteine regulator and a restorer of the body's osmotic balance. It has many uses in agriculture in animal/fish food.

TMG is a methyl-group donor and can be used to treat high homocysteine levels, to assist in the Re-methylation of Homocysteine back to Methionine pathway, turning the Homocysteine into Methionine and itself into DMG (dimethylglycine). This is the second of the two pathways (described above) to re-methylate homocysteine back into methionine. Betaine's role in this is to form part of the enzyme Betaine-Homocysteine MethylTransferase (BHMT). Supplementation with Betaine can assist in this remethylation capacity (assuming that other raw materials for BHMT are available).

TMG is commonly used with the amino acid lysine in livestock to decrease fat and increase muscle mass, although this effect has not been observed in humans with TMG.

http://en.wikipedia.org/wiki/Trimethylglycine

Betaine HCl is a common supplement to take for those with low levels of stomach acid, as described on the Digestion page. However, if one is taking large amounts of Betaine HCl, then this may convert additionally large amounts of Homocysteine back to Methionine. Clearly some Homocysteine is required to produce Cysteine (and Glutathione) as otherwise Cysteine/Glutathione production is not possible (e.g. inadequate methionine consmuption or too much Betaine consumption). However, in the majority of CFS cases, there is a lack of Glutathione (because of methylation problems rather than insufficient Homocysteine levels) and a massively excessive level of Homocysteine, so helping to reduce the amount of Homocysteine to Methionine is very useful; as well as folate and B12 supplementation to assist in the methylation process to convert more of this Homocysteine into Cystine and other essential downstream amino acids and peptides such as Glutathione and Hormones etc. One may elect also to take in more Glutathione precursors such as Cysteine-based products such as L-Cysteine or NAC, or perhaps even take a stabilised form of reduced Glutathione (GSH) to boost GSH levels (e.g. Tyler Recancostat).

It is probably wise to have an amino acid analysis profile, including the Homocysteine/Methionine cycle amino acids, performed by a reputable laboratory to determine the exact picture in this respect, to see which particular amino acids are deficient or in excess, and to determine the correct course of action. Please see the Identification page for more information.

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Antioxidants:

Free radicals are those particles and molecules that cause damage to the body's cells and essential fatty acids (e.g. EPA) by their oxidising ability. Oxidative damage is often associated with premature ageing and biochemical and DNA damage. Some examples of oxidative damage to cells can be found on the Identification page. Oxidative stress may not be a primarly cause of CFS or related conditions in most sufferers, but it is often a contributary factor. Oxidative damage is often much higher in those suffering from impaired liver function, heavy metal toxicity or who are heavily detoxifying the body (releasing heavy metals from the tissues). For an explanation of Free Radicals, Oxidative Stress and the body's own protective Antioxidants (known as Primary Antioxidants, please see the Oxidative Stress and Free Radicals page.

Dietary sources of antioxidant rich foods (known as External or Secondary Antioxidants) are essential in protecting against the effects of ageing and DNA and RNA oxidation.

www.netdoctor.co.uk/focus/nutrition/facts/oxidative_stress/oxidativestress.htm

Sources of external antioxidants include a variety of nutrients. Some of these are listed below, and crudely categorised for convenience:

One measurement used by some suppliers for antioxidative capability is the Oxygen Radical Absorbance Capacity or ORAC value. This is a direct measurement of ability to neutralise free radicals, and is a useful comparison scale for various food an supplement types. Not everyone cites the ORAC value of their products or foods/teas however.

http://en.wikipedia.org/wiki/Oxygen_radical_absorbance_capacity

A rough and ready guide to ORAC values can be found at the link below.

http://oracvalues.com/sort/food

ORAC values are clearly dependent on the concentration of a food source, and dried berries weight less than fresh berries, and so have higher ORAC values, even though they contain the same antioxidants berrry for berry. Plant extracts may also have a higher ORAC value than the original plant, and are also usually more expensive also. The ORAC values of fruits and berries fleshly plucked/picked will clearly be hugely higher than a processed supplement that reaches you via a supplement retailer. Below Dr Mercola examines the relative value for money of tropical berry extracts and supplements compared with one's indigenous fruits and vegetables.

http://articles.mercola.com/sites/articles/archive/2008/12/30/is-the-superfood-acai-worth-the-price.aspx

It should be noted that whilst cocoa beans are high in flavonols (polyphenols), they also contain high levels of the methylxanthines. The main methylxanthine in cocoa is Theobromine , which accounts for its cardiovascular supportive effects and mood elevation properties. Caffeine is another methylxanthine found in cocoa is lesser quantities. The caffeine content is less than ideal. Commercial chocolate also contains large amounts of sugar - milk chocolate hardly containing any cacoa at all). Cocoa beans will be higher in flavonols than roasted cocoa powder and indeed processed chocolates, as roasting in air will tend to oxidise antioxidants.

www.uncleharrys.com/infobase/product/cacao_beans.php

www.foodproductdesign.com/articles/465/465_0705INI.html

'Research on the role of phytonutrients gives considerable attention to the health contributions of cocoa and chocolate. Polyphenolics, particularly the antioxidant flavonoids that contribute to the health benefits of wine, coffee and tea also occur in significant, but inconsistent, levels in cocoa and chocolate. The flavonoid antioxidants are concentrated in the solids of the cocoa press cake rather than the cocoa butter. Oxidation of the flavonoids, some of which contribute to flavor, commences when the bean is removed from the seedpod and continues during roasting.'

The roasting process also renders Cocoa with more hot energy according to Traditional Chinese Medicine (TCM). Sugar free chocolate is available, containing Xylitol, for example, however, even natural plant (e.g. stevia) or sugar alcohol based sweetners may tend to aggravate dampness, qi deficiency and spleen meridian deficiencies, according to TCM.

Cocoa beans, cocoa powder and chocolate are also acidic, with a pH between 5 and 6, except for chocolate types found in baked goods that are pH adjusted so as not to interfere with the leavening process. Please see the Acidosis page for more information.

The benefits of controlling flavonoid oxidation have inspired some manufacturers to patent methods for selecting and protecting polyphenols and increasing their nutrient availability.

Ironically, at the end of the 19th Century and start of the 20th Century, the type of tea most commonly consumed in the UK was green tea. However, because of heavy advertising campaigns by manufacturers of black tea, the Edwardian population gradually shifted over to the consumption of black tea. This was not because of the taste, but because some disreputable tea firms were taking used green tea leaves, drying them out, and reselling them. Drinking 'black tea' was the 'only' way to be sure that you weren't drinking recycled tea leaves. And so black tea (much lower in antioxidants and higher in caffeine) predominated.

Vitamin C has been shown to protect the mitochondria inside cells from oxidative damage, and has even been shown to interfere with chemotherpay cancer treatment (which works on the basis of in relative terms indiscriminately oxidising/poisoning the body' cells, including the cancer cells). Many cancer treatments involve the use of antioxidants.

www.naturalnews.com/024380.html

The most powerful antioxidants are the body's own internally produced antioxidants, known as Primary Antioxidants, which target specific types of oxidative threats in the body, and are the most important down-regulators of oxidative stress in the body. They help to support proper liver function and the immune system. These Primary Antioxidants are the four in the list below. The most important of these are SOD, Catalase and Gpx. They are enzymes that break down oxidants, i.e. antioxidant enzymes. Melatonin is a antioxidant neurotransmitter and is also involved in the Circadian Rhythm (awake/sleep cycle).

The external antioxidants (i.e. those consumed and in some cases injected (e.g. Glutathione)), known as Secondary Antioxidants, are relatively less potent in their antioxidant capacity and are antioxidant chemicals. Perhaps the most effective approach is to prime the body to produce its own extra strength internal (primary) antioxidants, including SOD, Catalase and Gpx. These antioxidants provide the primary and most important level of defence against oxidative stress and free radical damage. Of course, a healthy diet and in particular one that is rich in Omega 3 and 6 fatty acids and other nutritious foods sources, with perhaps moderate amounts of green tea and algae, will also be high in antioxidants anyway. It is generally good practice to eat a diet rich in antioxidants and to take additional antioxidant supplement of one form or another.

For more information on the body's natural antioxidants, please see the Oxidative Stress page.

Pure-XP GliSODin is an example of a vegetarian form of SOD (based on a Melon juice extract) and according to manufacturer claims is not broken down in the stomach like other forms of internal antioxidants like SOD and Glutathione. Would it be cheaper to eat melons regularly?

www.glisodin.com

Catalase is an enzyme that breaks down Hydrogen Peroxide into water and oxygen.

Glutathione peroxidase (Gpx) is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water.

For more information on Glutathione Peroxidase and Superoxide, and their connection to mitochondrial function and cardiac function, please see the Cardiac Insufficiency page.

For information relating to Glisodin's ability to prevent DNA damage/mutation from UV exposure, please see the Exposure to Light section on the Stress Management page.

Please note that it is possible to take too many antioxidants, mainly if one is consuming supplement sources and plant extracts. This can result in a number of adverse effects including reduced ability to produce energy and a suppressed immune system. Antioxidants should be taken according to the body's balanced requirements and not in excess. Please see the Peroxynitrite page for more information.

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Fatty Acid Imbalances:

General

A fatty acid is a carboxylic acid (or organic acid), often with a long aliphatic tail (long chains), and is either saturated or unsaturated. Depending on the context, fatty acids may be assumed to have at least 8 carbon atoms, e.g., caprylic acid (octanoic acid). Most of the natural fatty acids have an even number of carbon atoms, because their biosynthesis involves acetate which has two carbon atoms. Industrially, fatty acids are produced by the hydrolysis of the ester linkages in a fat or biological oil (both of which are triglycerides), with the removal of glycerol.

Essential fatty acids, or EFAs, cannot be synthesised by the body, and must be obtained directly from food sources, and help to raise our good cholesterol levels in the body (High Density Lipoprotein). These include Omega 3 and Omega 6 fatty acids, which are polyunsaturated fats. Omega 7 and Omega 9 fatty acids are non-essential fatty acids, as they can be synthesised by the body from starches and sugars. Omega 7 and 9 fatty acids are mono-unsaturated fats and specific saturated fats.

As a general rule, polyunsatured fatty acids are powerful anti-oxidants and are linked with the reduction of cancer risk and even successful cancer treatment.

A saturated fat is one whose carbon chain is fully populated with hydrogen atoms and contains only single bonds, whereas an unsaturated fat has a carbon chain not fully populated with hydrogen atoms and contains one or more double bonds.

The body requires fats of the correct type and ratio for a variety of bodily functions and to maintain health. Essential fatty acids play an important part in cell membrane and brain composition. The consumption of sufficient essential fatty acids is necessary for efficient energy production, digestive function, good joint health, cell membrane function and fluidity, oxgen permeability and immune system functioning. Too many long chain saturated fats and trans fats in one's diet can result in displacement in cell membranes and brain tissue, altering the body's biochemistry and biochemical efficiency. Fatty acid imbalances may results in lower brain functioning (a gluey brain with too many long chain, rogue fats), fatigue, an impaired immune system, impaired mitochondrial (energy production) function, impaired cell membrane function (i.e. substitution of essential fatty acids with long chain fatty acids), impaired joint mobility, an impaired digestive system, a build up of atherosclerotic plaque in the arteries close to the heart, increased 'bad' cholesterol levels, and an increased cancer and heart disease risk.

It was formerly believed in the 1970s and 1980s that a low fat diet was the healthiest, and that keeping a low fat intake (simply avoiding fatty foods and instead eating low fat products) would help to prevent heart disease and reduce cholesterol levels. Unfortunately the media has over the last 30 years created the illusion that all fats are bad for you and is slowly starting to tell the real story. The vast majority of the population of the UK and many other industrialised countries consume too many 'bad' fats, those that are harmful to health and which increase blood cholesterol levels, but do not consume enough 'good' fats. Sufferers of depression in many cases find that simply changing their diet and consuming more 'good' fats, that they feel instantly better, and are cured in a matter of weeks! Fatty acid imbalances are often particularly marked in sufferers of CFS or related conditions. Please read on to find out more about 'good' and 'bad' fats. However, it has been found in studies that cholesterol levels and atherosclerotic plaque do not tend to decrease in those with low total fat diets, but stay the same.

www.benbest.com/health/essfat.html

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Omega 3

Omega 3 (n3 or w-3) fatty acids are polyunsaturated fats and include EPA (EicosoPentaenoic Acid), DHA (DocosaHexaenoic Acid) and ALA (Alpha-Linolenic Acid). EPA and DHA are fish derived and ALA is plant derived.

Omega 3 oils are easily oxidised by heat and exposure to light and air. This is why they are often purchased in darkened bottles. They should be stored in the fridge (or freezer) if they are not consumed relatively quickly. Heating or using an omega 3 rich oil is the worst thing you can do and not only does it ruin its nutritional value, but also makes it go rancid, destroying the fatty acid molecules, breaking them down into smaller molecules and producing a huge number of free radicals (which damage the body's cells and cause preamture ageing and oxidative stress). Oils high in Omega 3 should therefore be consumed cold and NEVER used for cooking (including ground Flax seeds). A list of oil sources rich in Omega 3 is included below. This is why frying with vegetable oil or corn oil or any other oil high in Omega 3 or 6 is very bad for you, on account of the high rancid fat and free radical content that arises through the heat of frying. Much better to simply steam then pour on room temperature oil - the food still has that oily taste and maintains its crispness through light steaming. Try it. If you compare the taste of a heated vegetable oil to an unheated one, at the same temperature, in the absence of the fried food, you will notice the fried/heated oil tastes rather unpleasant in comparison. This is why a product such as Udo's Choice Oil Blend should be kept in the fridge too (see below). One can taste an oil that has become rancid or oxidised because of the unpleasant taste. If an Omega 3 rich oil or food tastes like this, for example, has been stored too long, then dispose of it without hesitation.

http://en.wikipedia.org/wiki/Rancidification

http://www.westonaprice.org/knowyourfats/skinny.html

Omega 3 fatty acids come from a variety of food sources, such as marine foods and oily fish (and fish oils) (high levels of EPA and DHA), ground flaxseed/linseed, ground chia seed, oils (flaxseed/linseed oil is most potent vegetable source, also walnut oil, black currant oil, canola oil, pumpkin seed oil, soybean oil, wheat germ oil, macadamia nut oil - all sources of ALA), green leafy vegetables (such as lettuce, kale, purslane, spinach, broccoli, etc.), legumes (such as kidney beans, pinto beans, lima beans, mung beans, soya beans, split peas etc. - ALA), grass-fed beef, colostrum (DHA), and certain fruits such as citrus fruits, cherries and melons.

For example, Linusit Organic Linusprout (ground sprouted flaxseed) contains:

- 25% ALA (n3)
- 5% LA (n6)
- 21% Dietary Fibre
- 6% Monosaturated Fat (n9)
- 3% Saturated Fat
- 37% Carbohydrate
- 25% Protein

Flaxseed is high in the phytoestrogen known as Lignans. Whilst providing some antioxidant effect, these may also interfere with the body's endocrine system. Chia seeds are as rich a source of Omega 3 yet do not contain high levels of lignans so are probably preferable to take.

It should be noted that the human conversion of ALA to EPA and DHA is often quite slow and inefficient. In most cases, 15% of ALA converts to EPA and sometimes no ALA actually converts to DHA. The conversion may be inhibited by by too high an intake of Omega 6 fatty acids (i.e. LA containing foods - see below), trans fats such as deep fried foods, fast foods and baked goods, alcohol intake, and specific health conditions, and mineral and vitamin deficiencies (Vitamins B3, B6 and C, and zinc and magnesium). Vegetarians and vegans must therefore be especially careful in their diet. Fish are however a direct source of EPA and DHA. It is therefore recommended that fish based products are one's main source of Omega 3 fatty acids (ideally). Roughly 8% of the mass of the brain is made up of DHA. DHA availability is especially important in growing babies and children.

When taking EPA/DHA supplements, one may want to ascertain what the Dioxin and PCB toxin levels are, and indeed Mercury levels, as these may be present in significant levels in certain fish oil supplements.

www.food.gov.uk/multimedia/webpage/70427

There is some recent evidence to suggest that the bodys assimilation of EPA is inhibited when taken simultaneously with DHA (i.e. in fish oil). The research points to higher ratios of EPA to DHA result in much better the assimilation. Some special Omega 3 supplements (EPA is chemically isolated from the fish oil) contain only EPA and no DHA, and may be better than regular fish oil based supplements. In addition, they reduce the expose to the individual of excessive Vitamin A levels that can result from fish oil consumption (which is debated as to whether it is indeed harmful). Chris Masterjohn argues that high Vitamin A levels in Cod Liver Oil are no problem as they occur in a natural form (not artificially synthesized form) and are balanced with vitamins D and K.

www.cholesterol-and-health.com/Benefit-Of-Cod-Liver-Oil.html

DHA can be created from EPA as and when required by the body. Conversion from DHA back to EPA is however very difficult, but if sufficient EPA is consumed in the diet, then this is not a problem. An example of such a supplement is Igennus' VegEPA (which has a slightly misleading name because it is based on fish oil - perhaps the 'Veg' part refers to the small amount of Evening Primrose Oil that is added! Vegetarians take note! Talk about marketing people getting carried away.)

For those who do not regularly take fish oil, DHA or EPA supplements, or have not taken them for some weeks (e.g. if you took a break and switched to an ALA supplement (e.g. ground flaxseed) for a while), you may find that your stomach finds it a handful for a few days or up to a week, until it adjusts. This is certainly my experience, but of course may vary according to the individual.

Health Industry 'experts' have stated that a daily of intake of 500mg of either DHA or EPA (fish source Omega 3) is required (through food or supplementation) to ensure optimal health. ALA (plant sourced Omega 3) has less proven health benefits, although this may be hotly debated by vegans.

The links below discuss conversion from ALA to DHA and EPA, and related issues.

www.udoerasmus.com/articles/udo/fish_oil.htm

www.omega3sealoil.com/Chapter4_3c.html

One of the arguments against taking Cod Liver Oil is that many commercially prepared sources significantly oxidise the oil when it is being pressed from the fish livers on account of excessive contact with air and exposure to UV. High quality sources of Cod Liver oil significantly reduce the extent of oxidation and are frequently referred to as 'stabilised'. One example of a high quality Fish Oil supplement is Eskimo 3. Dr Joseph Mercola goes one step further and suggests that one should avoid fish oil completely and take Krill oil instead. Krill are shrimp-like curstaceans and are harvested mainly in the Antarctic. The Omega 3 fatty acids in Krill oil are attached to phospholipids as opposed to triglycerides in fish oil, making them more readily absorbed into the mitochondria and cell nucleus. The EPA/phospholipid molecule is also bound to Astaxanthin, an extremely potent antioxidant. According to Dr Moerck, Krill oil is 200 times more stable to oxidative damage than fish oil. Neptune Technologies is the Canadian company that holds the patent for krill oil extraction and most if not all Krill Oil supplements on the market are rebranded Neptune Krill Oil.

http://articles.mercola.com/sites/articles/archive/2010/10/16/rudi-moerck-on-fish-oil.aspx

www.fourhourworkweek.com/blog/2008/07/23/krill-oil-48x-better-than-fish-oil/

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Omega 6

Omega 6 (n6 or w-6) fatty acids are also polyunsaturated fats. The most beneficial of the omega-6 fatty acids are those that contain Linoleic Acid (LA). These are converted in the body to Gamma Linolenic Acid (GLA), another Omega 6 fatty acid. GLA and Arachidonic acid (AA), the third type of Omega 6 fatty acid, are ultimately to prostaglandins, which are hormone-like molecules that help regulate inflammation and blood pressure, as well as kidney, gastrointestinal, and heart functions, and thromboxanes, which are involved in platelet aggregation and blood clotting. Omega 6 fatty acids can tolerate some heat, but if overheated will turn rancid (as discussed above) creating a huge number of free radicals. Avoid roasting nuts mentioned below, e.g. peanut butter, or overheating groundnut oil in the pan etc.; or frying eggs; or frying with vegetable oils.

Good dietary sources of omega-6 fatty acids include cereals (LA), eggs (AA), peanuts, specific grains, nuts and seeds and their respective oils (i.e. groundnut/peanut, safflower, sunflower, corn, sesame seed, pumpkin, soya bean, walnut, wheatgerm, grape seed, pistachio nut, pecan nut, brazil nut, almond and macadamia nut - LA), Evening Primrose Oil (aka EPO) and starflower/borage oil (both contain LA and GLA), poultry, most vegetable oils (LA), colostrum (GLA), whole-grain breads (LA), baked goods (LA), algae (such as Chlorella and Spirulina - GLA) and margarine (LA). Please note that evening primrose oil and nuts contain abundant amounts of Vitamin E, so high dosages of EPO may result in a high Vitamin E intake.

Conjugated Linoleic Acid (CLA) is a conjugated form (an isomer) of linoleic acid, normally produced from modified Safflower oil. CLA aids in muscle deposition as opposed to fat deposition (reducing body fat and increasing lean muscle). CLA inhibits the enzyme that transports fat from the blood to fat cells. CLA may assist in lowering LDL cholesterol levels. Articles relating specifically to CLA can be found at the links below. CLA is sold as a weight control supplement. Testing on mice suggest that high intake of CLA may result in heart disease, but research is not conclusive in humans.

http://www.ironmagazine.com/review9.html

http://en.wikipedia.org/wiki/Conjugated_linoleic_acid

Research shows that grass-fed animal meat products are higher in Conjugated Linoleic Acid (CLA) than the grain and soya bean fed counterparts. Below is a relevant article from Weston A. Price Foundation's web site.

www.westonaprice.org/farming/splendor.html

www.seedsofhealth.co.uk/articles/healthy_beef.shtml

My friend Aaron is a major proponent of grass fed dairy and meat products.

With most people, getting enough Omega 6 fatty acids (in the form of LA) is not a problem, rather getting enough Omega 3 oils is more critical (as is illustrated futher below). Most Omega 6 fatty acids are consumed in the LA form, rather than GLA. If the vegetable and nut (oils) consumed are heated/baked/fried, then it is likely that much of the LA content may be become rancid. GLA may be hard for the body to produce from LA, and so GLA supplementation may be a good idea in certain individuals, even if LA consumption is high or 'sufficient'. If one is supplementing Omega 6, then it is probably much better to take a GLA supplement rather than one just containing LA.

Many beneficial oils such as black currant seed oil, borage oil, evening primrose oil contain GLA (Omega 6) as well as Omega 3 oils. Rarely does not obtain exclusively Omega 3 from any one source, but a mixture of Omega 3, 6 and 9 and other saturated fats. Please note that some of these Omega 6 sources also contain harmful trans fats, e.g. margarine (see below).

Somewhat confusingly, the term Linolenic Acid is used to describe both Gamma Linolenic Acid (GLA), an Omega 6 fatty acid, and also Alpha Linolenic Acid (ALA), an Omega 3 fatty acid. On this page, we refer to the specific types of Linolenic Acid.

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Omega 7

Omega 7 fatty acid, or Palmitoleic Acid, is a monounsaturated fatty acid and is one of the main types of oil produced by skin glands. Omega 7 does not need to be supplemented and can be produced from starches and sugars. Omega 7 and 9 fatty acids are usually found in the same food sources (see below).

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Omega 9

Omega 9 fatty acid, or Oleic Acid, is a monounsaturated fatty acid. Omega 7 does not need to be supplemented and can be produced from starches and sugars. It is the most abundant fatty acid found in nature and the main type of oil produced by skin glands. Sources of Omega 7 and 9 fatty acids include hazelnuts (78%), olive oil (72%), almonds (70%), canola oil (58%), avocado fruit (50%), macadamia nuts (45%), apricot seeds (35%), almonds (33%), sunflower oil (20%) and coconut oil (8%). Cocoa butter often contains oleic acid. Saturated fats are used mainly for energy production. Olive oil contains high amounts of Vitamin E, and so a large intake of olive oil may result in an elevated Vitamin E intake.

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Saturated Fats

Long-chain saturated fats come from both plant and animal sources and include fatty acids such as lauric acid (found in coconut oil), acetic acid (found in vinegar), stearic acid and palmitic acid. Animal sources probably make up the majority of sources of saturated fat for most people. Stearic acid is nature's most common long-chain fatty acid, and is a saturated fat that can be converted to oleic acid (Omega 9) which is monounsaturated. Palmitic acid constitutes 20-30% of most animal fats and is a major constituent of many vegetable oils (35-40% of palm oil). Saturated fats tend a high melting temperature and tend to be hard at room temperature, although some sources harden only at refrigeration temperature. Saturated fats are non-essential fatty acids and can be manufactured form monounsaturated and polyunsaturated fats in the body. Long chain saturated fats from food are only used for energy production and have no other nutritional purpose.

Animal sources of saturated fats included meat (especially red meats), seafood, whole-milk dairy products (cheese, milk, butter, yoghurt, ice cream etc.) poultry skin and egg yolks. Plant sources include coconut oil, palm oil, palm kernel oil, peanut (groundnut) oil and olive oil.

Palm kernel oil, palm oil and coconut oil are regarded as 'good' sources of saturated fats, because they are medium chain saturated fats (MCFA - medium chain fatty acids) and are metabolised differently in the body to long chain saturated fats (LCFA - long chain fatty acids). The majority of plant sources of saturated fats tend to be long chain fatty acids however. MCFA do not have the same properties as long chain saturated fats. MCFA are very different from LCFA. They do not have a negative effect on cholesterol and help to protect against heart disease. MCFA help to lower the risk of both atherosclerosis and heart disease. They also help to boost the immune system. It is primarily due to the MCFA in coconut oil that makes it so special and so beneficial. The MCFA in organic virgin coconut oil, for example, i.e. oleic acid (omega 9), lauric acid (saturated), capric acid (saturated), caprylic acid (saturated), also have antimicrobial and anti-viral properties (and is even used in assist in AIDS patients). Palm oil is the least desirable of the above oils as is a cheap ingredient used in commercial chocolate making and to make soap.

www.coconutresearchcenter.com

http://www.alternative-healthzine.com/html/0108_2.html

www.coconut-connections.com/research.htm

http://products.mercola.com/coconut-oil

www.westonaprice.org/knowyourfats/index.html

It should be noted that neither palm kernel oil, palm oil or coconut oil are 100% saturated fat, and so contain a proportion of polyunsaturated fats. Logic would dictate that the higher percentage of polyunsaturated fats an oil contains, the lower its smoking point with respect to cooking, but this is not necessarily the case. Not all polyunsaturated fats have the same smoking point, for instance. Also, it depends on whether the oil is refined or not, and refined oils, whilst not ideal for consumption cold, may make better oils for cooking as they tend to have a higher smoking point. Dry refined coconut oil has a smoking point of 204C, whereas dry expeller pressed virgin coconut oil has a smoking point of 177C. Coconut oil is classified as a 'Medium High Heat Oil' below, rather than a 'High Heat' oil, even though it has the least unsaturated fat.

There are a wide variety of oils that could be used for cooking but most are too obscure or expensive to make them good candidates. Refined sesame oil has a smoking point of 232C (perhaps why the Chinese tend to use toasted sesame oil for wok cooking), refined peanut (groundnut) oil has a smoking point of 232C, expeller pressed rapeseed (canola) oil 190-232C, and refined Safflower oil 266C! Clarified butter has a smoking point of 252C so is a good candidate for baking or frying. Avocado oil has a SP of 270C so if you can afford it, it is the best choice for cooking. When it comes to Olive Oil, high quality extra virgin olive oil with low acidity has a smoking point of 207C, so marginally better than coconut oil, whereas lower quality (more acidic) extra virgin olive oil is as low as 160C. Virgin olive oil has a smoking point of 199C. Refined soybean and semi-refined walnut oil are also reasonable candidates. Oils are in general best consumed unrefined and cold, but if you are going to use them for frying, then it is best to make a sensible choice. Coconut oil is heavily promoted in natural health internet circles as being the best oil for frying but this is exaggerated and more a case of wishful thinking because of the other beneficial properties of coconut oil.

https://en.wikipedia.org/wiki/Smoke_point

www.kokonutpacific.com.au/OilSales/OilCoconutoil/Oil_specs.html



http://www.spectrumorganics.com/images/uploads/Spectrum%20Mini%20Kitchen%20Guide.pdf

www.goodeatsfanpage.com/CollectedInfo/OilSmokePoints.htm

http://en.wikipedia.org/wiki/Cooking_oil

Bear in mind that excessive oil consumption puts a heavy burden on the liver and gallbladder. According to Traditional Chinese Medicine (TCM), excessive saturated fat intake, even 'good' saturated fats, can contribute to damp energy, and if the body has too much damp energy already, it can make one's condition worse. 'Bad' saturated fats are found in grain-fed animal produced butter, margarine and meats (especially red meats).

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Trans Fats

A trans fatty acid (often abbreviated to trans fat) is an unsaturated fatty acid molecule that contains a trans double bond between carbon atoms, which makes the molecule less kinked compared to fatty acids with cis double bonds. Transfats have no nutritional benefit but conversely are associated with a number of health risks.

The majority of trans fats in our diet are artificially produced, formed when food manufacturers turn liquid oils (polyunsaturated fats) into solid fats like hard margarine (i.e. hydrogenated vegetable based products). Hydrogenation of a polyunsaturated fat also increases the shelf-life. The harder the fat at room temperature, the higher the level of hydrogenation (and higher the amount of trans fats). Artificially producted trans fats include hydrogenated vegetable oils and margarine are often used in baked goods and fried fast foods. French fries or chips (as the Brits call them), or onion rings, tend to be cooked in hydrogenated vegetable oil. They typically contain up to 45% of their total fat content as trans fats. Bread and other baked products are usually produced with hydrogenated vegetable oils. Baked goods that are not made with trans fats are available if you look, but the vast majority aren't and are best avoided entirely.

Hydrogenated vegetable oil (trans fats) has been banned in Switzerland, Denmark and California, on account of strong links to increased risks of coronary heart disease, yet other countries still allow it to be used, affecting buyers of cheaper convenience goods who do not pay attention to labels or understand what all the ingredients are.

A small amount of trans fat (typically 2-5% of total fat content) is found naturally, primarily in dairy products, some meat, and other animal-based foods. Virtually all processed food and ready meals contain trans fats. When choosing the latter, try to find the product with hydrogenated fat or oil as low down on the ingredients list as possible. Avoid eating fried food when in restaurants as they often use partially hydrogenated vegetable oil in their fryers. Or ask what kind of oil they use.

Trans fats are defined on Wikipedia at the link below.

http://en.wikipedia.org/wiki/Transfats

Trans fats, like saturated fats, tend to have a high melting point (M.P.) and are usually solid at room temperature (e.g. certain cooking oils are often thicker after heating and subsequent cooling).

Trans fats and 'bad' saturated fats should be avoided as much as possible. They are a major contributor to atherosclerosis and coronary heart disease, and tend to decrease good cholesterol (High Density Lipoprotein - HDL) levels, whilst increasing bad cholesterol (Low Density Lipoprotein - LDL) levels. See the Cholesterol section below for more information.

Below is an article on Dr Mercola's web site about trans fats and how to avoid them.

www.mercola.com/2003/jul/19/trans_fat.htm

Below is a general overview of trans fats and cholesterol.

www.webmd.com/content/article/72/81813.htm

There is more information and discussion about trans fat content in our diet on the digestion page in the Processed Foods section.

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Importance of correct Omega 6 to Omega 3 Ratio

Omega 3 and 6 fatty acids compete for usage in the body. This is why it is important to consume them in the correct ratio. The optimum ratio is somewhere between 1:1 and 1:4 of Omega 3 to Omega 6. Some scientists argue that a 1:4 ratio is optimal for absorption of essential fatty acids. It is likely the exact ratio that is required perhaps depends on the individual. I have personally found 1:4 best, restoring EFA levels to normal, when they were previously deficient. Historically speaking, mankind has survived on a 1:1 ratio for tens of thousands of years. In most modern western diets, full of fried foods, high grain cotent and processed foods, the ratio is often somewhere in the region of 1:10 to 1:50. The high Omega 6 levels compared to Omega 3 are usually however based on LA consumption, and not GLA consumption, the latter being a probably much superior type of Omega 6.

Oils such as corn oil, sunflower oil etc are usually low in omega-3s, but contain significant amounts of Omega 6 oils and are most commonly used in cooking. An excess of Omega 6 fatty acids can have a serious detrimental effect on one's health. When there is a shortage of Omega 3 and 6 oils in the body, the human body compensates by producing more Omega 9 oils. This will over a period of time however be detrimental to your health. The correct ratio of Omega 3 to 6 oils will help to reduce the aches and pains of rheumatoid arthritis, combat free radical damage, reduce the symptoms of eczema and psoriasis, clear up acne and rosacea, relieve the discomforts of PMS, endometriosis, and fibrocystic breasts, improve digestion, regulate the liver, kidneys and endocrine system, improve the rate of tissue healing, increase muscle stamina, improve brain functioning, facilitate weight reduction, boost the immune system and prevent and improve diabetic neuropathy.

I myself was taking very large amounts of Omega 3, mainly in the form ALA, as well as Omega 6 in the form of GLA, and despite having a 1:1 ratio, found that his Omega 3 and 6 levels, especially 3, were dropping and not going up, and that the EFAs were simply not being absorbed effectively. This may be on account of the body's inability to convert ALA effectively when mitochondrial function is down, or it may be on account of the overly aggressive ratio. Probably a bit of both. When I changed the ratio to 1:4 and took mainly EPA instead of ALA, the Omega 3 levels normalised again. I therefore can only really recommend a ratio of 1:4 to other people, and preferably a DHA or EPA source of Omega 3.

Many oil supplements that contain Omega 3 and 6, or 3/6/9, tend to be biased towards a higher proportion of Omega 3, to compensate for the heavily tipped balance of Omega 6 to Omega 3 in most people's diets. However, if one eats well, and consumes reasonably significant amounts of EFA supplements, then one wants to ideally take a 1:4 ratio in my opinion. If the amount of DHA or EPA is very small, then taking such a supplement if usually fine, but if one is taking larger amounts e.g. pouring Udo's Choice oil (which has a 3 to 6 ratio of 2:1!), then it may result in excessive Omega 3 (ALA) levels and hence poorer absorption. Udo's Choice in my opinion is a great oil to use in copious amounts, if one is premixing it with organic Evening Primrose Oil, perhaps in a ratio of 1/3 Udo's to 2/3 EPO, which would give an optimal 1:4 Omega 3 to 6 ratio.

My practitioner, T Michael Culp, draws our attention to the fact that excessive consumption of ALA, from high flaxseed oil intake for example, has been shown to displace DHA and EPA from the cell membranes, which are far more important to membrane function. In addition, all Omega oils are long chain fatty acids (LCFAs) and require bile and enzyme outputs from the pancreas to digest. If one is supplementing oils high in omega fatty acids, then one shouldn't take too much, but may want to supplement medium chain fatty acids (MCTs) if one wants to gain weight or add calories as they do not require bile or enzymes to absorb. MCTs do not require the bile or enzymes to digest, and so do not strain the pancreas and gallbladder like LCTs do. Whilst Coconut oil is rich in MCTs, MCT oil is 100% MCTs and is an even better oil to use in my opinion than Coconut oil. The research that is often quoted to promote the use of Coconut oil is actually based on studies of MCT oil and not Coconut oil. MCT oil is also more antimicrobial, typically 55% Caprylic acid as opposed to 7% in Coconut oil. MCT is also more bland than Coconut oil and less warming than Coconut oil (possibly less hot and damp energy from a TCM perspective). It is generally used by bodybuilders as it is readily converted into energy and less converted straight into fat unlike LCTs of which generally a higher percentage is converted into fat. Some consider MCTs as more of a carbohydrate than a fat/oil.

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Cholesterol

There are two main types of cholesterol, or more specifically, compounds made from cholesterol that we are concerned with here that are made from cholesterol and protein, low-density lipoproteins (LDL) and high-density lipoproteins (HDL). When most people talk of cholesterol levels, they really mean the lipoprotein levels rather than the actual cholesterol itself which is a building block or building material for the body.

LDL carries cholesterol from the liver to the rest of the body. When there is too much LDL cholesterol in the blood, it can be deposited on the walls of the coronary arteries. This is why LDL cholesterol is often referred to as 'bad' cholesterol. LDL is a wax-like substance.

HDL carries cholesterol from the blood back to the liver, which processes the cholesterol for elimination from the body. HDL decreases the likelihood that excess cholesterol in the blood will be deposited in the coronary arteries. It also helps to remove LDL plaque that has been desposited from the artery walls. This is why HDL cholesterol is often referred to as 'good' cholesterol.

Cholesterol plays a vital role in the body, and is involved in the formation of cell membranes, all hormones and vitamin D. Clearly the body requires both LDL and HDL but in the right proportions and at the right levels.

In general, 25% of the (LDL) cholesterol in our blood comes from our diet. LDL cholesterol is found solely in animal products (meat and dairy). The other 75% of our blood's cholesterol is manufactured in our liver. The biggest influence on blood cholesterol levels is the type and mix of fats in our diet. Studies have also shown that in most people tested, an increase in cholesterol intake does not necessarily equate to any elevated levels of blood cholesterol levels (e.g. eating a couple of eggs per week). Vegetable products do not contain any cholesterol. Dietary cholesterol comes only from animal products, including meat, fish, milk dairy and eggs. Most of the cholesterol in the body is manufactured from fats, and not obtained or elevated significantly from dietary sources. Eggs in particular have not been found to elevate serum LDL levels, perhaps (specutively) partly because they contain Lecithin which is a fat emulsifier, and which inhibits its absorption.

As a general rule, (long chain) saturated fats (mainly animal fats) raise blood cholesterol levels more than dietary cholesterol as they boost levels of HLD AND LDL. The overall effect of boosting both is however negative.

Trans fats (mainly hydrogenated vegetable oils) greatly increase the amount of LDL in our blood (and decrease the amount of HDL), much more than actual consumption of cholesterol itself, and excessive consumption is a major contributor to heart disease and the lining of atherosclerotic plaque in our arteries. Trans fats are much worse for cholesterol levels than saturated fats. They also cause inflammation - an overactivity of the immune system that has been implicated in heart disease, strokes, diabetes and other chronic conditions. Whilst 'bad' saturated fats should be limited, trans fats (hydrogenated vegetable oils) and rancid fats (e.g. vegetable oils used for frying and deep frying) should be eliminated as much as possible.

Mono-unsaturated (Omega 9 fatty acids) and poly-unsaturated fats (Omega 3 and 6 fatty acids) greatly increase the amount HDL in our blood (and decrease the amount of LDL), thereby actively removing the atherosclerotic plaque from our arteries.

In addition, Phosphatidyl Choline (from soya lecithin) helps to reduce LDL levels and increase HDL levels in our blood. Antioxidants also play an important part in removing atherosclerotic plaque from the arteries. They do this partly by reducing the LDL to HDL. They also inhibit some of the oxidative/free radical damage to the arteries thus preventing hardening. This is discussed on the Peroxynitrite page. Soluble fibre, e.g. oats, also helps to reduce cholesterol levels by reducing the amount of saturated fats that are absorbed through the digestive system (as they tend to stick to the fibre).

Garlic has also been shown to raise HDL levels in the blood.

Niacin (Vitamin B3) has lipid modifying effects. In very high doses, e.g. 1-2g three times a day, can increase HDL cholesterol levels and lower VLDL levels (the precursor to LDL cholesterol).

Studies show that cholesterol levels and atherosclerotic plaque do not tend to decrease in those with low total fat diets (low total fat), but stay the same. This is because of the lack of EFAs in low total fat diets.

Plant sterols are a fashionable supplement, found in products such as Benecol and Flora pro-activ, and act to limit the uptake of dietary cholesterol (that which is consumed). However, as stated above, studies show that 75% of blood cholesterol is generated in the liver from trans fats and long chain saturated fats, and only 25% derives directly from cholesterol in the diet. In addition, a moderate increase in intake of dietary cholesterol does not usually have a significant effect on cholesterol levels in the blood. Thus seeking to limit cholesterol uptake from one's diet, and specifically, the meal which the plant sterol product is taken together with, will have little or no effect on actually lowering cholesterol levels in the blood. Studies also show that unless we are consuming enough sources of 'good' fats and oils, i.e. monounsaturated and polyunsaturated fats, then simply taking a plant sterols product in conjunction with one's regular diet will do nothing to boost our good cholesterol levels or to remove atherosclerotic plaque from the arteries. If one consumes a plant sterols product in conjunction with a healthy diet containing enough 'good' fats and limited long chain saturated fats and transfats, then it is will probably be beneficial. However, it is not necessary, and is probably marketed to 'lazy people' to lull them into a false sense of security that they can simply continue their normal unhealthy diet (high in long chain saturated fats and trans fats) and by simply taking plant sterols, they will be 'ok'. Plant sterols are no substitute to consuming enough good fats and to avoiding bad fats. Consumers are often easily fooled by advertising claims and seek a lazy way of becoming healthy (and being 'safe' from heart disease) which does not require any work or discipline. Plant sterol drinks typically contain glucose and sucralose (an artificial sweetner) as well, which is not very healthy from a gut flora, endocrine or toxicity perspective, e.g. Flora pro-activ. If one is to drink such a small quantity, why does it need to be sweet and palatable? Presumably to increase sales. The logic behind plant sterol drinks is that one needs to buy them indefinitely to keep one's blood cholesterol levels slightly lower (assuming the consumer does not change his diet which is highly likely) and as such is a cash machine. Plant sterol drinks as much a cure for all evils as the commercial probiotic drinks which are examined on the Digestive page. An article about plant sterols can be found at the link below.

www.patient.co.uk/showdoc/40002453

The latest guidelines from the National Cholesterol Education Program recommend the following optimal levels for adults over 20 years of age:

* Total cholesterol less than 200 milligrams per deciliter (mg/dl)
* HDL cholesterol levels greater than 40 mg/dl
* LDL cholesterol levels less than 100 mg/dl

The total required daily fat intake for an adult male is 95g, as opposed to 70g for an adult female.

An excellent article on the Harvard University web site on cholesterol and the role of EFAs can be found at the link below.

www.hsph.harvard.edu/nutritionsource/fats.html

As discussed above, consuming cholesterol does not automatically mean that one's blood cholesterol levels will increase. There are some arguments to suggest that eating foods high in cholesterol (not talking about saturated fats or trans fats but cholesterol itself) are actually good for you. A web site that promotes the idea of a high intake of dietary cholesterol being beneficial for health is listed below. Please note this is only discussing dietary cholesterol intake and not fatty acid types or LDL level.

www.cholesterol-and-health.com

An article which promotes a seemingly reverse trend, that high LDL levels are associated with a decreased risk of heart disease, is presented on the Weston A Price Foundation's web site at the link below. These arguments and research findings challenge the current view of LDL on the basis that those with high LDL levels show a higher mortality rate on account of their age and stressful lifestyles; and also on the basis that high cholesterol levels across different populations do not show the same trends with regards to heart disease. These are not widely accepted and may be regarded as somewhat contrarian in nature.

www.westonaprice.org/moderndiseases/benefits_cholest.html

The above article does not unfortunately relate the concept of high LDL levels to related areas. For example, how the people in the surveys actually achieved this high LDL levels; what their historical and current intake of different types of fatty acids was on average (i.e. monounsaturated, polyunsaturated, LCSFs, MCSFs, trans fats - relative quantities etc.); what their level of atherosclerotic plaque was like; what their cell membrane composition and health was like (easier to determine!) and what their brain tissue composition was like (hard to determine without killing everyone!); and lifestyle and other medical and psychological factors. The article does not really make it clear if all LDL is alike, or whether there are better and worse forms of LDL, depending on what precise fatty acids are used to make them up; or what the optimal ratio of HDL to LDL is - it seems to imply the more LDL the better. WAPF is not relying on its own research in this area however but on other parties' survey data and is adding an additional layer of interpretation. What is not in question with the Weston A Price Foundation's article is that monounsaturated and polyunsaturated fats are essential for health; and that cholesterol, HDL and LDL perform necessary functions in the body, which is why the liver produces them. What is therefore in question is saturated fat and trans fat intake but this is not mentioned. These fats do not just affect LDL levels but have other effects on the body. The uninitiated could read the article and assume that trans fat consumption was therefore good for your health, which it clearly isn't. Such basic distinctions should have been included! Without knowing any more specific information about the survey, it is difficult to comment. However, the findings from the University of Harvard Medical School are from 2006 and are more up to date.

Grass fed organic animal products are higher in Omega 6 fatty acids than their factory farmed or organic soya bean/grain fed counterparts, and as such are much better for you, despite still containing LCFAs. The high CLA content may well be responsible for their saturated fat content not resulting in quite as much LDL deposition as would otherwise be expected (see Omega 6 section above).

It may be hard to obtain organic, grass-fed meat and dairy products in any case, so for the majority of the population who do not eat such products, it is probably best to greatly limit saturated fat intake from red meat and dairy sources and to eliminate trans fat intake as much as possible, whilst consuming some limited 'good' sources of plant source medium chain saturated fats (e.g. palm oil or coconut). Food packaging shows the nutritional data about a type of food or food product, including the fat content and the proportion of this fat content that saturates (i.e. which is saturated fat). As a general rule then, it is probably wise to avoid foods with high amounts of fat that saturates, and stick to those with low % saturated fats of total fat content (e.g. low fat or fat free organic bio live yoghurt, most vegetable or nut sources, avoid red meats, etc.), with the exception of 'good' saturated fats such as in coconut and coconut oil. The % trans fat of total fat content is not normally displayed on food packaging and this is something that you must normally determine by looking at the ingredients (for hydrogenated or partially hydrogenated vegetable oils), by looking at how the food is to be cooked and your own common sense.

Aaron is a big proponent of eating significant amounts of grass fed animal products for health. It is up to the reader to make up his own mind. I have spoken with two individuals who have embarked on such diets high in grass fed animal products, and test results show very high LDL levels. Whether these are considered to be healthy or not is open to debate.

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Maintaining a good oil balance

Probably the ideal way to increase your Omega 3 and 6 levels are through consuming the foods that are rich in these oils (e.g. oily fish, fruit and vegetables, certain nuts or nut oils etc.), but in the right proportion to maintain the correct ratio. Try to carefully monitoring your food intake and its oil composition and type. Some practitioners recommend alternating sources of Essential Fatty Acids, on a 4 day rotation, as part of a Phospholipid Therapy programme, e.g. taking 2 tablespoons of a given oil per day; and starting off with Flax Seed Oil on day 1; Evening Primrose Oil on day 2; Pure Organic Omega Oil (a mixture of various plant based Omega 3 and 6 oils) on day 3; and Hemp Seed Oil on day 4. This however would result in an average ratio somewhere in between 1:1 and 3:1, but a fluctuating daily intake ratio. Other practitioners simply recommend taking a daily intake ratio of 4:1 and taking the same mixture of oils every day. One may wish to perhaps combine the best of both worlds, and alternate sources of oil every day, but keeping the ratio 4:1 for optimum absorption.

It is probably best to ensure you consume sources of EPA or DHA for Omega 3 and GLA of Omega 6 as these are probably the best types of each Omega 3 fatty acid. Experimental studies have shown that 3-4g of ALA per day is equivalent to 0.3g of EPA per day.

For example, one may wish to take EPA and GLA supplements to ensure a certain daily level of these fatty acids, and also to use certain vegetable or nut oils or oil mixtures that contain a broad spectrum of types of Omega fatty acids, in the correct ratios. Supplements and ground flaxseed packets list the composition by weight of different fatty acids, so it is quite easy to calculate approximately the correct ratio of supplements to take each day, if you understand what the terms actually are (which are all defined above).

At the end of the day, if you consume more calories than you are expending each day, you will put on weight and build up internal and subcutaneous fat; even if you are eating mainly good fats. It is therefore sensible to try to achieve the recommended daily fat intake of 70g for adult women and 95g for adult men, but not much more than this. A high fat and oil intake is going to be harder work for the liver, but especially so if this intake is high in bad fats. It is clearly best to try to make up as much of one's daily fat intake as good fats as opposed to bad fats.

Personally, I recommend to take Om3 and 6 in a 1:4 ratio, even when supplementing (many people recommend just supplementing Om3, but this does not guarantee that one is consuming a high quality source of Om6). Some supplemental options are listed below:

Below are some case studies of people who suffered from Depression, but after taking EFAs felt immediately much better. This includes Merrill Osmond.

www.drugawareness.org/Ribbon/Alternatives.html

www.vegepa.com/vegepa.php?n=WhynoDHAinVegEPA&indi=&ti=

Let us look at a few examples of EFA content of a few different supplements and calculating ratios. These supplements are examples and not necessarily being recommended. As we have discussed, most people have a general lack of Omega 3 in their diets compared to Omega 6 (e.g. little fish in one's diet). It is often recommended to have a total ratio of Omega 3 to Omega 6 of 1:4. Therefore if you are taking a relatively small amount of EFA supplements, then the actual Omega 3:6 ratio should be a little higher than this, so that the total intake ratio is around 1:4. However, if your blood is relatively low in EFAs, and you have problems absorbing them correctly, then your intake may need to be a little higher, in which case, if you are supplementing heavily with EFAs, then your ratio of Omega 3 to Omega 6 should probably be around 1:4 or thereabouts.

Igennus VegEPA
Each capsule contains:
560mg EPA (Omega 3)
200mg Evening Primrose Oil (EPO) - roughly equating to 160mg of Omega 6 fatty acids (GLA and LA)
Taking 1 capsule a day = 560mg Omega 3 and 160mg Omega 6.
Taking 3 capsules a day = 1.68g Omega 3 and 0.48g Omega 6.

Quest Evening Primrose 1000mg
Each capsule contains:
1000mg EPO = 820mg of GLA and LA (Omega 6)
Taking 1 capsule a day = 0.82g Omega 6
Taking 3 capsules a day = 2.46g Omega 6
Please be aware that EPO contains moderate amounts of Vitamin E.
Granovita Sprouted Ground Flaxseed
Each heaped plastic serving spoon contains 10g of ground flaxseed.
Flaxseed is made up of around 24% ALA (Omega 3) and 5% LA (Omega 6).
Therefore, one spoon contains 2.4g of Omega 3 and 0.5g of Omega 6.

[N.B. Sprouted Ground Flaxseed should not be refrigerated, but just kept sealed in a cool and dry place]

Nutrex Hawaian Spirulina powder
Each teaspoon is around 3g of Spirulina, containing 28mg or 0.028g of GLA (Omega 6). This amount is fairly negligible. Compared with the EFA contents of the other supplements listed above.

A daily intake of 3 x VegEPA capsules and 3 x Evening Primrose Capsules therefore provides a total intake of 1.68g Omega 3 and 2.94g Omega 6, giving a Omega 3 to 6 ratio of 1:1.75.

A daily intake of 1 x VegEPA capsule, 3 x Evening Primrose Capsules and 6 x BodyBio PC capsules therefore provides a total intake of 1.28g Omega 3 and 5.5g Omega 6, giving a Omega 3 to 6 ratio of 1:4.3.

We hope that these examples give you the general feel for calcuating your supplemental intake of Omega 3 and 6. Supplements always list the 3 and 6 content or at least the weight of each individual EFA. So once you know what each fatty acid is (defined above as to whether they are 3 or 6), the total can be easily calculated.

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Phospholipid Deficiencies:

Phospholipid therapy is a nutritional therapy, a mitochondrial therapy, a neurological system therapy and also a detoxification therapy. In the latter application it helps to release partial detoxification products attached to the cell membranes. Please see the Detoxification Protocols page for information relating to dietary Phospholipid requirements and Phospholipid therapy in individuals with environmental illnesses, particularly those with high levels of free radical damage and oxidative stress. Tips on phospholipid supplementation can be found there, in addition to links to a number of technical articles and papers about Phospholipids, which are well worth a read.


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