Betaine (trimethylglycine (TMG)) is a natural occurring compound found in certain foods. The body is also able to synthesize it from the vitamin choline.
Betaine has been shown to improve body composition, muscle size, work capacity, but not strength in trained men.
Betaine is a major osmolyte in the cell and maintains cellular hydration to protect myosin ATPase and myosin heavy chain (MHC) proteins against denaturation by urea during metabolic stress (1).
It regulates the cell volume, stabilizes proteins, lowers inflammation, is involved in the synthesis of creatine and improves energy metabolism by supporting the synthesis of carnitine (which is necessary for the transport of long-chain fatty acids to the mitochondria where they are oxidized for energy).
Betaine lowers homocysteine
Choline can rapidly be converted to betaine via choline dehydrogenase and betaine aldehyde dehydrogenase.
Betaine is then used in the methylation of homocysteine to methionine. This pathway is mediated by BHMT, an enzyme induced by betaine. Another nutrient that’s important for homocysteine conversion to methionine is folate. Once betaine is used to methylate homocysteine to methionine, it creates DMG. Methionine is then converted to S-adenosylmethionine (SAM). SAM is the major methyl donor in the cell. It is involved in numerous cellular reactions, including DNA methylation and synthesis of phosphatidylcholine, and in reactions involving neurotransmitters, creatine, carnitine, and antioxidants (such as glutathione and taurine).
Both DMG and SAM inhibit DHMT. So as SAM increases, DHMT activity decreases and visa versa. So SAM concentrations are maintained by stimulating the BHMT pathway (2). A small amount of DMG is eliminated in the urine, and most DMG is converted via DMG-dehydrogenase into sarcosine and glycine.
A choline deficiency reduces liver SAM by 60% (3), which just indicates how important adequate choline is for betaine synthesis. The body can however synthesize choline from phosphatidylethanolamine to phosphatidylcholine and into choline, but SAM is also used in this process. All of this will result in low methionine and SAM levels, due to inadequate dietary choline consumption, even when adequate folate is present.
The body can only use a certain amount of betaine at a time no matter how much choline you have or how much betaine you ingest. Betaine is stored in the cells and hence is always a ready-to-use methyl group source. Folate, which also assists in the methylation of homocysteine to methionine, decreases the amount of betaine needed. So folate takes the load off betaine and vise versa.
A large dose of betaine (4 g/day) for three months caused no additional lowering of homocysteine when given with 5mg folic acid and 50mg vitamin B6 compared to 5mg folic acid and 50mg vitamin B6 without betaine.
This study shows that acute supplementation of a small dose of 550 mg betaine slightly lowered circulating homocysteine and increased DMG, with minimal levels of betaine appearing in the urine, suggesting that betaine was metabolized and partly stored in tissues (4).
There is clearly only a certain amount of betaine needed for proper methylation. Is it then necessary to supplement with extra betaine after all when a diet rich in choline and folate is consumed?…
Betaine exerts a choline and methionine sparing effect. The methionine-sparing effect of betaine makes methionine more available for protein synthesis, nitrogen retention, and creatine synthesis. And the choline-sparing effect makes choline more available for lipid metabolism (export fat from liver to be burned for energy). This will result in better hypertrophy and fat loss. Choline is very important for many other functions, so sparing it will be most beneficial. More about choline here.
Betaine supplementation has been shown to be useless in gaining muscle in sedentary individuals. But once you start to exercise, the metabolic demands for betaine, methionine, SAM, choline, vitamin B6 and B12 increase.
Betaine is also able to correct insulin signaling by activating insulin receptor substrate 1 (IRS1) by increasing tyrosine phosphorylation and other signaling mechanisms that regulate gluconeogenesis and glycogen synthesis (5). Elevated homocysteine directly impairs insulin signaling by reducing insulin receptor substrate-1 (IRS-1) activation and thus inhibiting Akt-phosphorylation (6). Betaine will ensure homocysteine levels stay low and that it doesn’t interfere with insulin receptors by making you more insulin sensitive.
Eating a diet low in methionine will increase BHMT activity to increase methionine production. Eating a methionine rich diet has shown to increase homocysteine which leads to decreased mRNA expression and muscle protein synthesis, unless adequate methyl donors such as betaine and folate are present to methylate homocysteine to methionine. Ingesting 500 mg of betaine decreased fasting plasma homocysteine and attenuated homocysteine rise for 24 hr following a methionine load in healthy adults (7). Eating too much protein can actually inhibit muscle protein synthesis and put you in a negative nitrogen balance by elevating homocysteine, even when sufficient methyl donors are present. That’s why it’s so important to only eat enough protein for your body’s needs. And yes you will need more protein if you train intense. If you lose your taste for protein, cut back, until you regain the desire to eat meat. It’s your body telling you that it’s getting too much protein.
Consuming betaine and folate rich foods together with betaine supplementation is able to lower homocysteine more than just betaine supplement alone.
Betaine doesn’t just boost hypertrophy through proper methylation but also by being able to elevate plasma GH and IGF-1, and increase Akt phosphorylation in skeletal muscles (8).
I think a betaine supplement can be of much use and benefit. Remember not to neglect your diet and consume lots of raw egg, liver and wheat germ oil for adequate choline and betaine.
Best dietary source of betaine includes: wheat germ and wheat germ oil, spinach, beets and quinoa
Dosage: 2.5g a day is shown to be adequate for hypertrophy and fat loss.