Unless your major is college was chemistry, chances are you don’t remember learning about methyl donors. But if you find the field of brain nutrients and anti-aging interesting, you will certainly want to learn more about these supplements. A methyl donor is simply any substance that can transfer a methyl group [a carbon atom attached to three hydrogen atoms (CH3)] to another substance. Many important biochemical processes rely on methylation, including the metabolism of lipids and DNA. Scientists suspect that adequate methylation of DNA can prevent the expression of harmful genes, such as cancer genes. It’s quite likely that our body’s ability to methylate declines with age, contributing to the aging process, and therefore supplementation could well be beneficial. The research in this area is still very early and no firm answers are yet available.
In chapter 9 of Mind Boosters, I mention two of the B vitamins, folic acid and B12, to be methyl donors. Here I discuss four additional nutrients involved in methylation: TMG, DMG, SAM-e, and DMAE. All but SAM-e have been sold over the counter for a number of years. SAM-e became available in the US in 1996. Interestingly, some vegetables, such as onions, garlic, and beets, contain methyl donors.
What can Methyl Donors do for You?
Methyl donors help in the production of several brain chemicals and hence improve mood, energy, wellbeing, alertness, concentration, and visual clarity. A few people notice sexual enhancement.
What conditions or diseases can methyl donors benefit?
They may be helpful in age related cognitive decline, Alzheimer’s disease, fighting depression, and overall health maintenance. They may perhaps also be helpful in Parkinson’s disease. However, the more is not necessarily better. As with most supplements, a proper balance is important since too high doses can have unpleasant side effects such as overstimulation and insomnia.
DNA methylation has been thought to be an underlying molecular mechanism that may account for the effect of dietary factors on the development and prevention of heart disease. DNA methylation is an epigenetic process that provides "marks" in the genome by which genes are set to be transcriptionally activated or silenced. Epigenomic marks are heritable but are also responsive to environmental shifts, such as changes in nutritional status, and are especially vulnerable during development. S-adenosylmethionine is the methyl group donor for DNA methylation and several nutrients are required for the production of S-adenosylmethionine. These methyl nutrients include vitamins (folate, riboflavin, vitamin B12, vitamin B6, choline) and amino acids (methionine, cysteine, serine, glycine). As such, imbalances in the metabolism of these nutrients have the potential to affect DNA methylation.
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Trimethylglycine TMG and Dimethylglycine DMG
TMG, also known as betaine, is basically the amino acid glycine attached to three methyl groups. Dimethylglycine is similar to trimethylglycine, except it has two methyl groups. You may recall that a methyl group is a carbon attached to three hydrogen atoms (CH3). Both of these nutrients are powerful methyl donors. Methylation is an important factor in many biochemical processes in the human body. In chapter 9 I mentioned that the B vitamins folic acid and B12 lower levels of homocysteine, the harmful amino acid-like substance in blood which can cause hardening of the arteries and possibly damage brain cells. By reducing homocysteine levels, the risk for heart disease can be reduced. TMG and DMG are also known to reduce homocysteine levels and therefore could be helpful in reducing the rate of heart disease. It’s possible that as we age, the process of methylation becomes less effective and supplementation with TMG or DMG may provide health and anti-aging benefits.
Methyl donors are also involved in the making of brain chemicals which accounts for their cognitive effects. My clinical experience confirms that both TMG and DMG improve mood and energy. Brian, a 29-year-old laboratory technician from Torrance, California, speaks for many when he says, “TMG gives me more energy and clearer thinking. There’s a sense of wellbeing that comes on that lasts all day.” Paul Frankel, Ph.D., co-author with Fred Madsen, Ph.D., of a book on methylation, says, “I’ve been taking TMG since 1995 at a dose of 250 mg a day. Through my interviews with individuals who have taken TMG, I have come across many who report benefits—sleeping better, having more energy, and experiencing less chronic fatigue. TMG could also jump start some people and help them fight their depression. A woman whose daughter was suffering with depression told me ‘TMG gave me my daughter back.’” Dr. Madsen adds, “ I have taken TMG for more than ten years without any side effects. People who take TMG report that their mood is enhanced.”
TMG and DMG are underutilized methyl donors that hold a great deal of promise but unfortunately, few doctors are familiar with these nutrients. At this time the clinical uses of TMG and DMG are not well defined and whether they would be helpful in the therapy of Alzheimer and Parkinson’s disease is not known. Since the body’s ability to methylate declines with age, supplements of TMG or DMG in small amounts, such as 50 to 100 mg a day, may benefit middle aged and older individuals.
I recommend not exceeding 250 mg of TMG or DMG on a daily basis until more is known about these supplements. Your dose of TMG and DMG should be reduced if you are taking B vitamins, SAMe, DMAE, or choline since all of these nutrients have overlapping functions and many have the ability to be methyl donors.
SAMe, a compound made from the amino acid methionine, is a methyl donor involved in the synthesis of dozens of important compounds in the body. SAMe has been available by prescription in Europe for many years as an antidepressant but has been available over the counter in the US only since about 1996.
Unlike other methyl donors where the research is scarce, there have been a number of studies with SAMe. These studies have shown that it influences brain chemicals by helping to convert norepinephrine to epinephrine and serotonin to melatonin, helping make creatine, an important energy reservoir in muscle tissue, and helping the preservation of glutathione, an important antioxidant. Furthermore, SAMe is involved in the formation of myelin, the white sheath that surrounds nerve cells and can improve the brain cell membrane fluidity, thus potentially enhancing the function of receptors (Cestaro 1994).
SAMe and Mood
Because of its role in the making of neurotransmitters, SAMe has been tested in the therapy of depression. A number of studies have been published, mostly in Europe, evaluating this nutrient’s role in mood disorders. Back in 1994, Dr. Bressa, from the University Cattolica Sacro Cuore School of Medicine, in Rome, Italy conducted a meta-analysis of the studies on SAMe (Bressa 1994). A meta-analysis is a statistical pooling of already published research papers. Dr. Bressa concludes, “The efficacy of SAMe in treating depressive syndromes and disorders is superior to that of placebo and comparable to that of standard tricyclic antidepressants. Since SAMe is a naturally occurring compound with relatively few side-effects, it is a potentially important treatment for depression.”
A major drawback to the use of SAMe is the expense. The retail price is about a dollar per 200 mg pill. The suggested dose in the therapy of depression ranges from 100 to 400 mg a day. Many nutrients work is a similar fashion to SAMe, particularly other methyl donors such as DMAE, TMG, DMG, and also some of the B vitamins. In fact, B12 and folate help the body produce SAMe. Therefore, your dosage of SAMe should be reduced if you are taking other methyl donors.
SAMe has a good potential in becoming a useful therapeutic methyl donor for depression and age related cognitive decline. Long-term studies are needed with SAMe before making widespread recommendations for its use. However, short-term human studies thus far have found it to be safe and effective. A major drawback to the long-term use of SAMe is its cost. Keep in mind, though, that TMG and DMG are also powerful methyl donors, work in a similar fashion, and are cheaper. Could TMG or DMG, taken along with B vitamins, offer similar benefits to SAMe at a fraction of the cost? It is known that TMG can help regenerate SAMe (Barak 1996). Dr. A. Barak and colleagues, from the Department of Veterans Affairs Medical Center, in Omaha, Nebraska, say, “In view of the fact that SAMe has already been used successfully in the treatment of human maladies, TMG, being a SAMe generator, may become a promising therapeutic agent and a possible alternative to expensive SAMe.”
A lot more research has to be done with SAMe to confirm some of the preliminary findings listed above. Dr. Bottiglieri and colleagues, from Baylor Research Institute, in Dallas, Texas, published a review article on SAMe and other methyl donors (Bottiglieri 1994). They summarize, “SAMe is required in numerous methylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B12 metabolism, and deficiencies of both these vitamins have been found to reduce central nervous system SAMe concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, and peripheral neuropathy. Studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders.”
Known chemically as dimethylaminoethanol, DMAE has been known in Europe by the product name Deanol for more than three decades. DMAE has two methyl groups and is chemically similar to choline. This methyl donor has been popular for many years among those interested in improving mental alertness and clarity of thinking.
One double blind, placebo-controlled trial performed with in twenty-seven patients with severe Alzheimer's disease did not show any significant benefits (Fisman 1981). Another study on twenty-one patients with memory deficits was also discouraging since no improvement was found in memory (Caffarra 1980). However, DMAE was found helpful in patients with age related cognitive decline. This nutrient was given in a dosage of up to 600 mg three times a day for four weeks to fourteen older patients (Ferris 1977). Ten patients improved and four were unchanged. The patients on DMAE had reduced depression, less anxiety, and increased motivation, but they had no improvement in memory. The researchers say, “the results thus suggest that although DMAE may not improve memory, it may produce positive behavioral changes in some senile patients.” Dementia is a term that is now substituted for senility and is sometimes used to denote a severe case of age related cognitive decline.
As you can see, limited studies with DMAE have not shown it to be effective on Alzheimer’s disease or to help memory, however, DMAE does seem to help improve mood and motivation in older patients with dementia.
DMAE can be helpful in the elderly who have cognitive decline. This nutrient can also be taken by an adult of any age who needs to be more focused and alert.
Methyl donors are very interesting nutrients with a great deal of potential, particularly as antidepressants. Since our body’s ability to methylate declines with age, it’s possible that they may someday be found to have anti-aging benefits (Cooney, 1993). These nutrients can also be taken on days when one needs to be more focused and alert.
In addition to their effects on the mind, methyl donors, along with B vitamins, can help lower homocysteine levels, thus reducing the risk for certain heart and neurological diseases.
Not to be confused
There are a number of compounds with methyl groups. These include methyl salicylate, methyl benzoate, methyl alcohol, methyl bromide, methyl methacrylate, methyl orange, methyl ester, methyl paraben and others. I am not sure of the actions of some of them and do not know whether they also act as methyl donors. I guess I should have paid more attention in my college chemistry class.