Pharmacology of Betaine

  
Pharmacology of Betaine 

Introduction:

After the successful trials by Thyagarajan et al and Bloomberg et al on Phyllanthus niruri for eradication of hepatitis B surface antigen from chronic carriers, there was a spate of search for herbs useful for eradication of hepatitis viruses. After completing my monograph on Methee-Fenugreek (Trigonella foenum-graecum L), I happen to read the importance of betaine as a hepatoprotective phytochemical present in Methee-Fenugreek (Trigonella foenum-graecum L). Due to unavoidable reasons it was not possible to incorporate the information in the monograph hence I decided to write a separate article on betaine.

Other Names:
Betaine Hydrochloride, Trimethyl Glycine (TMG), 2 (N, N, N-trimethyl) ammonium- acetate, Betaine Anhydrous, Glycine Betaine, Glycocoll Betaine, Glycylbetaine, Lycine, Cystadane, Oxyneurine and many more. [1], [2]

Phytochemistry:

Betaine (pronunciation: BEET-uh-een)

Molecular formula of Trimethylglycine: C5H11NO2

Structural formula of Trimethylglycine:


Betaine is a neutral chemical compound related to quaternary ammonium compounds.
It is a white crystalline powder freely soluble in water.

Trimethylglycine (TMG) is an organic compound that occurs in plants. It was the first betaine discovered by science. Originally it was simply called betaine because it was discovered in sugar beets. Subsequently many other betaines have been discovered.

Betaine anhydrous is found in beets, spinach, cereals, seafood and wine [3], [4]

Mechanism of Action:
Betaine anhydrous a form of betaine helps in the metabolism of homocysteine. Betaine anhydrous prevents the buildup of homocysteine seen in people with inborn disorder of homocysteine metabolism [5]

Pharmacology:

TMG is an important co-factor in methylation processes required for the biosynthesis of neurotransmitters, melatonin, and coenzyme Q 10. The major step in the methylation cycle is the remethylation of homocysteine. Betaine is thus involved in the synthesis of many biologically important molecules.   

The U. S. Food and Drug Administration (FDA) has approved it to be used as a drug for hyperhomocysteinemia, homocysteinuria, osteoporosis, some musculoskeletal problems and some ophthalmic problems. [6], [7]

Intracellular accumulation of betaine permits water retention in cells thus protecting them from the perils of dehydration. Although supplementation of TMG or betaine decreases the amount of adipose tissue in pigs, research on human subjects has not shown satisfactory results. It lowers high blood levels of homocysteine and also is useful in the treatment of homocystinuria. Betaine hydrochloride was sold as a “stomach acidifier and digestive aid” but it does notincrease gastric acid secretion. Two clinical trials have indicated that TMG may be useful for the treatment of NASH. TMG is sometimes used to treat depression.

Betaine hydrochloride is also used to treat hypokalemia, hay fever, anemia, bronchial asthma, atherosclerosis, gallstones, otitis interna, RA, thyroid disorders and liver disorders. [8]

Application of cream containing specific betaine daily for one month before exposure to ultraviolet rays can reduce the redness caused by UV rays. However applying the cream only 20 minutes before exposure does not have any effect.

Using betaine anhydrous in toothpaste can reduce dryness of mouth. [9]

Some Testimonials from Modern Research

Betaine and Alcoholic Liver disease

Chronic intake of alcohol decreases the concentration of S-adenosylmethionine (SAM), increases the plasma concentrations of homocysteine. [10]

Betaine can convert homocysteine to methionine. Thus betaine decreases the plasma concentration of homocysteine and hepatic concentration of methionine. This leads to increased SAM:SAH ratio and attenuates the development of fatty liver, hepatic inflammation and fibrosis. [11]

The mitochondrial dysfunction plays an important role in the pathogenesis of Alcoholic Liver Disease (ALD). Betaine preserves the mitochondrial function and prevents ALD. [12]

Chronic alcohol intake increases gut-derived endotoxin in the portal circulation activating Kupffer cells to produce several proinflammatory cytokines. Alcohol also leads to the synthesis of Toll-like receptor 4 (TLR4) protein that contributes to alcohol-induced liver injury. Betaine antagonizes these alcohol-induced insults and prevents ALD. [13]

Betaine and NonAlcoholic Fatty Liver Disease (NAFLD)

In an experimental study on mice by reducing glucose, insulin, triglycerides and hepatic fat betaine prevented NAFLD. [14]

Dietary supplementation of betaine specifically enhances insulin sensitivity in adipose tissue. Further study revealed that betaine supplementation alleviated high-fat-diet-induced endoplasmic retinaculum stress response in adipose tissue. [15]

Betaine and HBV

Only a small data exhists about the role of betaine in the histological, serological and clinical effects of betaine hepatitis B virus- infected patients. [16]

Betaine and HCV

In chronic hepatitis C hyperhomocysteinemia is an independent risk factor for steatosis and and even hepatic fibrosis. As seen above betaine reduces homocysteine levels. Thus betaine can eliminate one risk factor of liver injury associated with hepatitis C infection. [17]

It is suggested that betaine can be an important adjuvant to conventional anti-viral treatment of hepatitis C infection. This can also overcome the problem of drug resistance. [18]

Toxicity:
Betaine/ TMG  is not free from side effects. TMG supplementation may cause stomach upset, nausea and diarrhea. Total cholesterol levels may be increased in obese persons and in those suffering from kidney disease. [19], [20], [21]

There is no enough reliable data about the safety of taking betaine during pregnancy.
Betaine can cause nausea, stomach upset and diarrhea in children
Betaine anhydrous can increase levels of total cholesterol and low-density lipoprotein. [22]

Uses

·        Betaine anhydrous has been approved by the U. S. FDA to be used as a drug for the treatment of hyperhomocystenemia. It is available as standardized chemical at a set dose in capsule form.
·        For homocystinuria: In children, beginning with 100mg/kg per day the dose is gradually increased weekly. A maintenance dose is 3 grams twice a day in both children and adults
·        Betaine anhydrous is used in toothpastes to reduce the symptoms drymouth.
·        Betaine anhydrous is used to improve athletic performance, treat depression, congestive cardiac failure, hyperhomocysteinemia, liver diseases and to prevent adenomas of the colon  


References:

1. https://en.wikipedia.org/wiki/Betaine
2. http://www.webmd.com/vitamins-supplements/ingredientmono-1008-betaine%20anhydrous.aspx?activeingredientid=1008&activeingredientname=betaine%20anhydrous#
3. https://en.wikipedia.org/wiki/Betaine
6. https://en.wikipedia.org/wiki/Betaine
10. V. Purohit, M. F. Abdelmalek, S. Barve et al., “Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium,” American Journal of Clinical Nutrition, vol. 86, no. 1, pp. 14–24, 2007. 
11. Z. Wang, T. Yao, and Z. Song, “Involvement and mechanism of DGAT2 upregulation in the pathogenesis of alcoholic fatty liver disease,” Journal of Lipid Research, vol. 51, no. 11, pp. 3158–3165, 2010. 
12. K. K. Kharbanda, S. L. Todero, A. L. King et al., “Betaine treatment attenuates chronic ethanol-induced hepatic steatosis and alterations to the mitochondrial respiratory chain proteome,” International Journal of Hepatology, vol. 2012,
13. A. Dolganiuc, G. Bakis, K. Kodys, P. Mandrekar, and G. Szabo, “Acute ethanol treatment modulates Toll-like receptor-4 association with lipid rafts,” Alcoholism, vol. 30, no. 1, pp. 76–85, 2006. 
14. E. Kathirvel, K. Morgan, G. Nandgiri et al., “Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine,” American Journal of Physiology, vol. 299, no. 5, pp. G1068–G1077, 2010. 
15. Z. Wang, T. Yao, M. Pini, Z. Zhou, G. Fantuzzi, and Z. Song, “Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease,” American Journal of Physiology, vol. 298, no. 5, pp. G634–G642, 2010. 
16. Evidence-Based Complimentary and Alternative Medicine, Volume 2012, Article ID 837939, 19 pages, http://dx.doi.org/10.1155/2012/837939
17. F. H. T. Duong, V. Christen, M. Filipowicz, and M. H. Heim, “S-adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro,” Hepatology, vol. 43, no. 4, pp. 796–806, 2006. 
18. D. Graf, K. Haselow, I. Münks, J. G. Bode, and D. Häussinger, “Inhibition of interferon-α-induced signaling by hyperosmolarity and hydrophobic bile acids,” Biological Chemistry, vol. 391, no. 10, pp. 1175–1187, 2010.
19. http:// en.wikipedia.org/wiki/Trimethylglycine
20. http:// en.wikipedia.org/wiki/Betaine
21. http://www.webmd.com/vitamins-suppliments





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