The Benefits Of Betaine

A couple walking hand in hand down a country path. Betaine may help them in this health.

Betaine anhydrous (Bet) is a naturally produced compound. Supplementation with betaine is most often used for reducing blood homocysteine levels and trying to improve athletic performance.

It is a quaternary ammonium compound and a methyl derivative of the amino-acid glycine when it combines with choline. Its formula is (CH3)3N+CH2COO. The main characteristic is that three methyl groups are attached to the molecule. It has a molecular weight of 117.2g per mole.

Sources: A significant component of beets, shellfish and other seafood, spinach, cereals especially wheat including its flour and wine (Zeisel et al., 2003). It is often supplemented into protein powders and pre-workout shakes.

Other names: trimethylglycine, glycine betaine, lycine, and oxyneurine.

Betaine acquired its name because it was first found in sugar beet (Beta vulgaris) in the 1800s.

Betaine helps in the metabolism of homocysteine. The compound is approved by the U.S. Food and Drug Administration (FDA) for treatment of high urine levels of a compound often produced in the body called homocysteine. The condition is called homocystinuria. This condition occurs in people with certain inherited disorders. High homocysteine levels are associated with heart disease, weak bones  as in osteoporosis, other skeletal problems, and eye lens problems.

Betaine In Literature

The role of betaine is very well reviewed by Stuart Craig in the American Journal of Clinical Nutrition (Craig, 2004). The book by Preedy (2015) on betaine is also worth consulting and there is a more recent review of clinical studies by Day and Kempson (2016). A very comprehensive examination has also become available by Zhao et al., 2018.

Function Of Betaine

An organic osmolyte which protects cells subjected to stress (Eklund et al., 2005). Recent research indicates that because of this osmolytic role it might be an importnat modulator of hippocampal neurophysiology and neuroprotection. The implication is that it helps to protect certain aspects of brain physiology (Knight et al., 2017).

A source of methyl groups obtained by transmethylation for use in a variety of biochemical pathways. That role is similar to the B vitamins, folate and vitamin B12 (cobalamin) which are also methyl donors. The role of betaine is especially important in the liver which is an organ with the role of detoxifying nasty chemicals and ensuring the correct cellular functioning of the body. It also most importantly helps the body to metabolise fats.

Betaine is found in both plants and animals which is a testament to its universal role mainly as an agent in cells to protect them from death because of osmotic inactivation.

The daily intake of betaine in the human diet ranges from  1g/ day to a high of 2.5 g/d. The higher levels are ingested when the diet is based on shellfish and whole wheat (Craig, 2004).

Betaine And The Treatment Of Homocystinuria

Betaine  is a supplement and an effective means for treating homocystinuria (Sakamoto et al., 2002) where it lowers plasma levels of homocysteine.

Homocysteine is naturally produced in the body – it is an amino acid in its own right. It helps to convert homocysteine to another amino-acid methionine. Whilst amino-acids are important for building proteins such as enzymes and structural proteins like collagen, too much homocysteine damages blood vessels. That can lead to the formation of plaque and this artherosclerosis amongst other cardiovascular related diseases (Williams et al., 2004).

It prevents seizures in animals induced by a variety of agents including  electroconvulsive shock, pentylenetetrazol and strychnine.

Effects On Body Composition

Betaine is added to animal feeds to produce more meat by increasing the lean muscle mass and decreasing the fat (Eklund et al., 2005;  Ratriyanto et al., 2009).

Two studies have looked at the effects of betaine on body composition and hypertrophy in humans. Supplementation did not improve body composition in obese, sedentary subjects on a 500 kcal/day caloric deficit following 12 weeks of supplementation (Schwab et al., 2002). Similarly, 10 days of supplementation did not improve body composition in sedentary young male subjects (del Favero et al., 2011).

Betaine Supplementation In Sports By Improving Exercise Performance

Betaine has gained considerable popularity in recent years for its performance enhancing properties as well as improving body composition and strength. It has a role in many ways similar to creatine. The supplement is used to help replenish muscle cells especially in preventing them dehydrating and improving their endurance to a small extent. For some athletes this can mean a few extra yards or seconds gained although there is still plenty of research to be conducted on the compound.

Studies in rats indicate that supplementation with betaine helps in the regulation of one-carbon metabolism and reduces accumulation of fats in the liver if a high-fat diet was followed (Deminice et al., 2015). It also has a role in suppressing oxidation and other inflammatory processes associated with alcoholic liver fibrosis (Bingül et al., 2016).

However, at the moment the benefits in improved exercise performance are still weak. It might help with experienced athletes but to date there are no studies to support any improvement in strength in untrained men for example. Also, betaine does not appear to improve the ability to rehydrate after long distance running or sprinting.

Betaine And Cancers

There is insufficient evidence that supplementation with betaine helps reduce the risk of development of any tumors especially of the colon and rectum as claimed in some web-sites. This is based on a suspicion that it prevented the formation of noncancerous lesions such as colorectal adenomas.

Treatment Of Viral Diseases

  • Hepatitis C.

Early research suggests that taking betaine anhydrous (Cystadane) and SAMe together with hepatitis C medications for 12 months can reduce the amount of active virus in people with hepatitis C who did not respond to treatment with hepatitis C medications alone. There is not yet enough evidence though to support the claim.

Betaine And Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver (NAFL) is a common liver disease, associated with insulin resistance. The compound has been investigated for its possible treatment of NAFL in animals (Kathirvel et al., 2010). It was found that treatment improved insulin levels and thus helped with management of blood glucose which is turn has also led to the suggestion that it is another diabetes management tool (Kharbanda et al. 2009).

There have been some small scale trials but the results are too mixed to support a major benefit.

Brain Health

We mentioned earlier about the the benfits of having an osmoregulating chemical in the brain for protecting certain structures.

Schizophrenia is a chronic psychiatric disorder with a multifunctional genetic and  neurobiological background. The condition impacts early brain development and is expressed as a  combination of psychotic symptoms—such as hallucinations, delusions and disorganization (Simonneau, 2019).

One of the most recent pieces of research has highlighted a potential benefit in the treatment of schizophrenia (Ohnishi et al., 2019). The reason of the research comes from observations that betaine is lowered in patients with this mental disorder. Could it be a novel psychotherapeutic agent ?

Supplements Based On Betaine.

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References

Bingül, İ., Başaran-Küçükgergin, C., Aydın, A. F., Çoban, J., Doğan-Ekici, I., Doğru-Abbasoğlu, S., & Uysal, M. (2016). Betaine treatment decreased oxidative stress, inflammation, and stellate cell activation in rats with alcoholic liver fibrosis. Environmental Toxicology and Pharmacology, 45, pp. 170-178. (Article). 

Cholewa, J. M., Wyszczelska-Rokiel, M., Glowacki, R., Jakubowski, H., Matthews, T., Wood, R., … & Paolone, V. (2013). Effects of betaine on body composition, performance, and homocysteine thiolactone. Journal of the International Society of Sports Nutrition10(1), 39. (Article)

Craig, Stuart A.S. (2004) Betaine in human nutrition. American Journal of Clinical Nutrition, 80 (3), 1 September, Pages 539–549 (Article

Day, C. R., & Kempson, S. A. (2016). Betaine chemistry, roles, and potential use in liver disease. Biochimica et Biophysica Acta (BBA)-General Subjects, 1860(6), pp. 1098-1106.

Del Favero S, Roschel H, Artioli G, Ugrinowitsch C, Tricoli V, Costa A, Barroso R, Negrelli AL, Otaduy MC, da Costa Leite C, Lancha-Junior AH, Gualano B (2011) Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids

Deminice, R., Da Silva, R. P., Lamarre, S. G., Kelly, K. B., Jacobs, R. L., Brosnan, M. E., & Brosnan, J. T. (2015). Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism. Amino acids, 47(4), pp. 839-846. (Article

Eklund, M., Bauer, E., Wamatu, J., Mosenthin, R (2005) Potential nutritional and physiological functions of betaine in livestock. Nutr. Res. Rev. 18 pp. 31-48. 10.1079/NRR200493

Kathirvel, E., Morgan, K., Nandgiri, G., Sandoval, B. C., Caudill, M. A., Bottiglieri, T., … & Morgan, T. R. (2010). Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine. American Journal of Physiology-Gastrointestinal and Liver Physiology299(5), G1068-G1077 (Article)

Kharbanda, K.K., Todero, S.L., Ward, B.W., Cannella, J.J., Tuma, D.J. (2009) Betaine administration corrects ethanol-induced defective VLDL secretionMol Cell Biochem 327: pp. 75–78 (Article)

Knight, L. S., Piibe, Q., Lambie, I., Perkins, C., & Yancey, P. H. (2017). Betaine in the brain: characterization of betaine uptake, its influence on other osmolytes and its potential role in neuroprotection from osmotic stress. Neurochemical Research42(12), pp.  3490-3503 (Article)

Lever, M., & Slow, S. (2010). The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clinical Biochemistry43(9), pp. 732-744.

Ohnishi, T., Balan, S., Toyoshima, M., Maekawa, M., Ohba, H., Watanabe, A., … & Shimamoto-Mitsuyama, C. (2019). Investigation of betaine as a novel psychotherapeutic for schizophrenia. EBioMedicine. (Article)

Olthof, M.R., van Vliet, T., Boelsma, E., Verhoef, P. (2003) Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J. Nutr. 133: pp. 4135-4138 (Article

Preedy, V.R. (2015) Betaine: Chemistry, Analysis, Function and Effects. RSC. Cambridge.

Ratriyanto A, Mosenthin R, Bauer E, Eklund M. (2009) Metabolic, osmoregulatory and nutritional functions of betaine in monogastric animals. Asian-Austral. J. Anim. Sci. 22 pp. 1461–76

Sakamoto, A., Nishimura, Y., Ono, H., Sakura, N. (2002) Betaine and homocysteine concentrations in foods. Pediatr.  Int. 44 pp. 409–13 (Article)

Schwab U, Törrönen A, Toppinen L, Alfthan G, Saarinen M, Aro A, Uusitupa M. (2002) Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am. J. Clin. Nutr. 76 pp. 961-967 (Article)

Simonneau, M. (2019). Translational research identifies a metabolism pathway involved in first-episode of schizophrenia: Towards precision medicine. EBioMedicine46, pp. 19-20 (Article).

Sprince, H., Parker, C.M., Josephs, J.A. Jr. (1969) Homocysteine-induced convulsions in the rat: protection by homoserine, serine, betaine, glycine and glucose. Agents Actions. 1 pp. 9–13 (Article). 

Virtanen E. (1995) Piecing together the betaine puzzle. Feed Mix  3 pp. 12–7.

Yancey, P.H., Clark, M.E., Hand, S.C., Bowlus, R.D., Somero, G.N. (1982) Living with water stress: evolution of osmolyte systems. Science 217 pp. 1214–22 (Article

Williams, J.R., Howe, J., Zeisel, S.H. et al., (2004) Betaine Concetration of Common Foods in the US. Poster. IFT conference. Las Vegas. (Article

Zeisel, S.H., Mar, M.H., Howe, J.C., Holden, J.M (2003) Concentrations of choline-containing compounds and betaine in common foods. J. Nutr. 133: pp. 1302-1307.

Zhao, G., He, F., Wu, C., Li, P., Li, N., Deng, J., … & Peng, Y. (2018). Betaine in inflammation: mechanistic aspects and applications. Frontiers in Immunology9.  (Article)

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