Creatine & B-Vitamins

Creatine synthesis consumes the body’s methyl reserves

The creatine synthetic pathway is shown in the figure below. Creatine is synthesized in two steps: (Step 1) arginine and glycine combine in the kidney to produce GAA; (Step 2) GAA next travels through the blood stream to the liver where it is methylated to produce creatine.

Creatine supplementation spares SAM and lowers serum homocysteine levels

Homocysteine, a byproduct of creatine synthesis, adversely influences health. Importantly, homocysteine levels are attenuated by creatine supplementation, which circumvents creatine synthesis, and by certain B-vitamins, which help recycle homocysteine back into methionine, or to convert it into cysteine (and then to glutathione, an important antioxidant).
AGAT= arginine:glycine amidinotransferase; GAMT = guanidinoacetate methyltransferase
GAA: Guanidinoacetic acid

Step 2 in creatine synthesis is the single greatest drain of the body’s methyl reserves, accounting for a loss of up to 75% of all available methyl groups. Therefore, endogenous creatine synthesis can potentially exhaust the body’s precious methyl reserves!

The importance of cellular methylation

Creatine is one of the most important products of biological methylation. Other indispensable methylation products include adrenaline, carnitine, melatonin, certain neurotransmitters, blood lipids, growth factors, anabolic hormones and the nucleic acids (DNA and RNA), from which all components of life are created. Many of these methylation products are intimately involved in muscle growth and development!


Succinctly put, without methylation all biosynthesis would come to a screeching halt. Given these far reaching ramifications, it is not surprising that merely interfering with the body’s ability to methylate specific targets results in severe birth defects, weakness, dementia, neurodegenerative diseases, coronary-vascular disease, liver disease, renal disease, cancer as well as accelerates the decline in motor and mental capabilities associated with advanced age. Obviously, life itself depends on methylation!

The universal methyl-donor supporting these reactions is a molecule known as S-AdenosylMethionine, or SAM. SAM is a modified form of the essential amino acid, methionine.
Read a recent issue of the Creatine Newsletter discussing the polyamines, extremely potent anabolic agents that are produced via multiple methylation steps.

Creatine supplementation boosts cellular methylation status

Creatine supplementation, since it circumvents the need to synthesize creatine, spares our body’s SAM reserves and indirectly supports other important methylation reactions. It is very likely that much of the ergogenic benefit typically observed with creatine supplementation has to do with its positive effect on methylation status…

Click here for a description of how imbalances in cellular methylation status can be detrimental to one’s health.

B-vitamins similarly enhance cellular methylation status

Certain B-vitamins (B-2, B-6, B-9 and B12) promote methylation by participating in key enzymatic reactions that either recreate SAM, or help dispose of homocysteine. B-vitamins thus have an effect similar to that of creatine supplementation, which, by relieving the need to synthesis creatine from basic substrates, spares the body’s SAM reserves.

At the same time this group of B-vitamins also makes creatine synthesis more efficient, since they aid in neutralizing homocysteine (a potentially dangerous compound) while increasing the availability of SAM. In theory therefore, one can take less creatine when supplementing with B-vitamins to optimize cellular methylation status. Taking smaller doses of creatine, on the other hand, will also avoid the stress that conventional supplementing regimens place upon your system. A low-dose creatine regimen is given in our creatine guide.

Combine creatine with B-vitamins for optimal gains


For optimal results, you need to consume a product containing a very specific combination of vitamin B6, folic acid and vitamin B12 as well as a dosage based on your sex, weight, age and fitness objective. Additionally you need to cycle these vitamins (similarly to creatine supplements) to get the desired effects.

Click here for information about a new product designed with this method of creatine optimization in mind.

Click here to have a vitamin B dose calculated to fit your particular set of physical parameters.

Click here for a discussion of creatine’s other ergogenic benefits.

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