October 4, 2004
1- Featured Article: Creatine. Not just for jocks anymore…
This Month’s Featured Article:
Creatine. Not just for jocks anymore…
by Alfredo Franco PhD
Methylation reactions are extremely important to life. Surprisingly, despite their utmost importance, these reactions are really quite simple. Methylation reactions merely entail the addition of a methyl group (one carbon with three hydrogens, or CH3), via the actions of an enzyme (a protein catalyst), to an appropriate biomolecule. Many important biological molecules are substrates for methylation reactions. For instance, methylation functionalizes proteins, produces neurotransmitters, is essential for the functioning of our genes, and put the finishing touch on the building blocks that form our cellular membranes. Obviously, life would not be possible without these reactions.
The Mother of all Methylation Reactions
One of the most important methyl donors in the body is the essential amino acid, methionine (hence, the meth in methionine). For example, methionine adds a methyl group to GuanidinoAcetic Acid (GAA) to produce alpha-MethyGuanidinoAcetic Acid, which, when translated, simply means a molecule of GuanidinoAcetic Acid with a methyl group attached at the alpha position. Do not let the name throw you, however, alpha-MethyGuanidinoAcetic Acid is nothing more than an overly descriptive name for CREATINE. Creatine, therefore, is just another, of many, important biological molecules that are activated with the addition of a methyl group. In fact, creatine synthesis is the major consumer of methyl groups in the body.
Note: For those interested, methionine functions as a methyl donor in the activated form of S-AdenosylMethionine, or SAM; methionine attached to an adenosine group.
The importance of methionine, therefore, stems from its role as a methyl donor, and, consequently, dietary methionine intake is necessary for overall good health. Furthermore, to help assure an uninterrupted supply of methionine, the body has devised a contingency plan. When the dietary intake of methionine is insufficient to meet the body’s needs, methionine can also be obtained by modifying another molecule known as homocysteine. In essence, homocysteine is a methionine molecule lacking its signature methyl group. Adding a methyl group to homocysteine, in turn, effectively reforms methionine. Homocysteine thus serves as a reserve source of methionine to be used when dietary intake is low- a very important role.
Note: The importance of methionine to muscle functioning is demonstrated by the finding that methionine deficiencies are associated with stunted muscle development, a fact that the livestock and poultry industries have been well aware of for quite some time.
The Bad News…
Few things in life, however, are ever perfect… Normally, serum homocysteine levels fall within a very narrow range of 8-12 microMolar. By contrast, only a slight increase in blood homocysteine levels is strongly correlated with increased incidences of several human diseases. For instance, clinical research has shown that elevated serum homocysteine levels are strongly indicative of the chances of developing Coronary Heart Disease (CHD) in later life. In fact, just a small (5 microMolar) increase in serum homocysteine levels increases the chances of developing CHD by 60% in men and an incredible 80% in women. Elevated plasma homocysteine levels are also associated with the development of Alzheimer’s disease, increased risk of hypertension, neurological defects, dementia, loss of cognitive function, as well as renal and liver disease. It is obviously a wise idea to keep your homocysteine levels under control.
The Good News…
Importantly, the presence of methionine channels homocysteine through its degradation pathway. The end-product of homocysteine degradation is the amino acid, cysteine, and accounts for the fact that cysteine is not an essential amino acid, at least, not while sufficient methionine is present in the diet. In this respect, consuming foods rich in methionine should help lower plasma homocysteine levels by increasing the levels of methionine in the blood stream. Dietary methionine intake will also assure the presence of cysteine for protein synthesis. Luckily, fish is one of the best sources of dietary methionine.
However, another very effective way of increasing serum methionine levels is to prevent its participation in creatine synthesis (review second paragraph, if necessary). Conversely, allowing creatine synthesis to proceed simultaneously consumes serum methionine and elevates plasma homocysteine levels. In fact, some experts have estimated that endogenous creatine synthesis is responsible for producing 75% of the total homocysteine present in humans.
Note: The cellular reactions that both produce methionine and degrade homocysteine are very sensitive to the B vitamin complexes, namely B<sub6</sub>, B<sub>12</sub>, and Folic acid. The B vitamin complexes are also very important to cellular energy metabolism. Therefore, supplementing your diet with B vitamins will help keep plasma homocysteine levels in check as well as extend exercise capacity.
Alternatively, choosing a creatine product containing B vitamins and essential amino acids (methionine) will be even more effective at reducing serum homocysteine levels and promoting muscle development than pure creatine monohydrate alone. In this respect, I have recently caught wind of a new product that contains both these sets of ingredients. I will keep you informed as I learn more of its release onto the market.
The Even Better News…
Creatine supplementation is one of the most effective ways of inhibiting creatine synthesis. Creatine supplementation, should therefore raise plasma methionine levels, depress plasma homocysteine levels, and, hence, improve overall cardiovascular health.
In the early days of creatine research, this aspect of creatine supplementation was perceived as possibly deleterious, since it shut down a very important biochemical pathway, i.e., creatine synthesis. Indeed, this once dark cloud now appears to have developed a silver lining. ‘In light’ of these recent findings, the inhibition of creatine synthesis in response to supplementation, might, instead, be yet another potentially healthful attribute of creatine supplementation.
Creatine supplementation appears to be an effective strategy to reduce serum homocysteine levels, a powerful risk factor for vascular and coronary heart diseases. Elevated serum homocysteine levels are also associated with the increased incidences of Alzheimer’s, hypertension, neurological developmental defects, dementia as well as renal and hepatic disorders.
Creatine supplementation will thus mount a two-pronged attack on vascular and coronary heart disease. Firstly, creatine, by way of extending our capacities to exercise, reduces insulin-resistance, lowers harmful serum cholesterol levels, raises our metabolic rate, burns fat and, overall, reduces the risk factors for these diseases. Secondly, creatine now appears to reduce plasma homocysteine levels directly, which should further contribute to a reduced risk of developing vascular and coronary heart disease later on. Creatine is turning out to be very ‘Heart Smart’.
Brosnan J.T., Jacobs R.L., Stead L.M., and Brosnan M.E. (2004) Methylation demand: a key determinant of homocysteine metabolism. Acta Biochimica Polonica. Volume 51(2), pages 405-413
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