Nitric Oxide Donor Therapy

Trimethylglycine

Sources

Betaine is obtained by humans from foods, either as betaine or as choline-containing compounds. The best sources of betaine per 100g of food are:

Food

Betaine per 100g

Quinoa

630mg

Spinach

577mg

Wheat-bran cereal

360mg

Lamsquarters

332mg

Beets

256mg

Betaine can also be created during the breakdown of choline. The conversion of choline to betaine is a two-step enzymic process, which occurs in the liver and kidney. Choline is first oxidised to betaine aldehyde, a reaction catalysed by the mitochondrial choline oxidase (choline dehydrogenase, EC 1.1.99.1). In a subsequent step, betaine aldehyde is further oxidised in the mitochondria or cytoplasm to betaine by betaine aldehyde dehydrogenase (EC 1.1.1.8).

Daily Intake

Estimates of betaine intake are from 0.1 to 1 g/day and as high as 2.5 g/day for a diet high in whole wheat and seafood. Thus, the intake depends on food composition but is probably also related to production of the food items, including growing and osmotic conditions.

Functions

Betaine has three known functions in mammals: It is an organic osmolyte that accumulates in renal medullary cells and some other tissues to balance extracellular hypertonicity. Second, it acts as a chaperone to stabilise protein structure under denaturing conditions. Third, it serves as a methyl donor in the betaine homocysteine methyltransferase (BHMT) reaction, which converts homocysteine to methionine. Betaine is also present as an osmolyte in high concentrations (10s of millimolar) in many marine invertebrates, such as crustaceans and molluscs, and acts as a potent appetitive attractant to generalist carnivores such as the predatory sea-slug Pleurobranchaea californica.

Therapeutic uses

Anhydrous trimethylglycine (called Cystadane) is approved by the FDA to treat homocystinuria, a disease caused by a birth defect in which homocysteine levels are too high. Laboratory studies and two clinical trials have indicated that TMG is a potential treatment of nonalcoholic steatohepatitis.

Many scientific papers have speculated on other potential uses for this substance, but none of these ideas have passed the drug approval process or been approved by the FDA. However, trimethylglycine (aka betaine) is available as a dietary supplement, and there is a great deal of confusing discussion on the internet about ways that this substance might be useful to “treat” certain diseases or conditions. As mentioned above, none of these uses have been approved by the FDA. Although betaine supplementation decreases the amount of adipose tissue in pigs, research in human subjects has shown no effect on body weight, body composition, or resting energy expenditure, calling into question its usefulness as a fat loss aid.

In the veterinary/food production field, TMG is used by the ton in livestock farming, paired with lysine to increase “carcass yield”, thereby helping increase muscle mass. It is also used in salmon farming, to relieve osmotic pressure in cells, as the animals make the switch from freshwater to saltwater.

Side Effects

Most side effects from betaine aren’t dangerous and include diarrhea, stomach upset, and nausea. Those suffering from kidney disease should not take the supplement, because when taken with folic acid and vitamin B6, it can increase total cholesterol levels. This also is an important concern for people who are overweight or obese and they should take betaine only under the supervision of a knowledgeable health care provider.

Biochemical mechanisms

TMG is an important co-factor in the methylation cycle, a process in every cell in the body which synthesizes and donates methyl groups (CH3) to various processes in the body. These processes include the synthesis of neurotransmitters such as Dopamine, Serotonin and Taurine, the detoxification agents Glutathione and Cysteine, the energy-enhancing CoQ10 and the sleep-inducing hormone Melatonin.

The major step in the methylation cycle is the remethylation of Homocysteine which has two pathways. The major pathway is via the Methionine Synthase enzyme which requires B12 specifically, and folate and various other B vitamins indirectly. The minor pathway is via Betaine Homocysteine Methyltransferase which requires TMG/betaine as a co-factor. Betaine is thus an important element in the synthesis of many chemicals in the body, particularly if the major pathway is diminished.

Uses in molecular biology

Trimethylglycine can act as an adjuvant of the polymerase chain reaction (PCR) process, and of all other DNA polymerase-based assays such as DNA sequencing. By an unknown mechanism, it aids in the prevention of secondary structures in the DNA molecules, and prevents problems associated with the amplification and sequencing of GC-rich regions. Trimethylglycine makes guanosine and cytidine (strong binders) behave with thermodynamics similar to those of thymidine and adenosine (weak Binders). It has been determined under experiment that it is best used at a final concentration of 1M .

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