Betaine combined with key B vitamins may protect cardiovascular health

Maintaining a healthy body requires a whole range of nutrients. Some compounds work better when combined with others. These synergistic blends accentuate the positive health benefits of each element.  Also, many processes within the body require several different compounds to function optimally. When one of these components is in short supply, the whole mechanism can be compromised. One combination of nutrients that may have added benefits for cardiovascular health is betaine together with the vitamins B6 (pyridoxine), B9 (folic acid) and B12 (cobalamin).

What is Betaine?

betaineBetaine, sometimes referred to as betaine anhydrous or trimethylglycine (TMG), is a neutral chemical compound that was first isolated from beetroot. It’s made in the body and helps to regulate the liver and support cellular reproduction.

This compound also assists to manufacture the amino acid carnitine and metabolise homocysteine. These roles have attracted attention of cardiovascular researchers. Preliminary studies suggest that betaine may have potential to help reduce the risk of atherosclerosis when combined with key vitamins.

The effects of excess homocystine on arteries

The amino acid homocysteine is manufactured within the body. Excessive amounts of this compound have been associated with the development of blood clots and atherosclerosis.  This is because an oversupply of homocysteine, known as hyperhomocysteinemia, will lead to hardening of the arteries. Homocysteine is produced by reactions between the amino acid methionine and vitamins B6, B9 and B12.

Excessive homocysteine levels can be caused by a range of factors. Some of these include poor diet, smoking, excess alcohol and caffeine intake, diabetes, dysfunctional thyroid, rheumatoid arthritis and certain medications. Chronic inflammatory diseases are also often associated with elevated homocysteine concentrations.

Regulating homocysteine levels

The process of metabolising homocysteine in the body is complex. It relies on vitamin derived cofactors.  Elevated blood plasma levels of homocysteine have been shown to occur when there is an absorption deficiency of vitamin B12 and a dietary deficiency of vitamin B6 and B91.

When there are adequate concentrations of these B vitamins the circulating levels of homocysteine are easily regulated and maintained at healthy levels. This is because homocysteine is rapidly metabolised by one or two different pathways:

Homocysteine can be regenerated into methionine through a re-methylation pathway dependant on B9, B12 and betaine.

Homocysteine can be converted to cysteine through a vitamin B6 dependant trans-sulphuration pathway.

Studies show that by increasing the availability of vitamins B6, B9 and B12 plasma concentrations of homocysteine can be reduced to a healthy level2.

How does betaine work to regulate homocysteine?

Betaine is involved in the re-methylation pathway in the kidney and liver cells to lower homocysteine levels3. The betaine-homocysteine methyltransferase (BHMT) pathway facilitates the transfer of a methyl group from betaine to homocysteine, producing dimethylglycine and methionine4. Approximately 25% of homocysteine is metabolized by this pathway.

Several studies have shown that betaine supplementation can help to stabilise circulating homocysteine concentrations5, 6. Increasing the dietary intake of foods rich in this compound is also proven to reduce plasma homocysteine levels7.

When combined with B9, betaine supplementation appears to have a great effect on lowering homocysteine concentrations than if administered independently8. For the re-methylation pathway to function effectively, the body must have adequate concentrations of betaine, B6, B9 and B12.

Important dietary sources

The best food sources for betaine include beets, broccoli, spinach, shellfish and whole grains. Vitamin B6 can be gained from fish, beef liver, starchy vegetables and non-citrus fruits. Many foods are now fortified with foliate (B9) to try and boost the availability of this key nutrient. Natural sources include fatty fish, leafy greens, legumes, eggs, nuts, soy products and lean meats. Vitamin B12 can be sourced from fish, poultry, meat, milk, and eggs. This vitamin is in low levels in plant foods, although fortified breakfast cereals are a common dietary source.

A word of caution

Betaine supplements may cause an increase cholesterol levels9. This could counteract the positive effects of lowering plasma homocysteine.  Hence, it is very important that anyone considering supplementation with betaine, B6, B9 and B12 that they first consult a doctor to rule out any potential underlying health concerns.


Arthrosclerosis causes the narrowing and hardening of the arteries. This substantially increases the risk of heart disease, blood clots, stroke and heart attacks.  The amino acid homocysteine has been linked to increased risks of arthrosclerosis if unregulated. Maintaining healthy levels of homocysteine requires a series of chemical reactions in the re-methylation pathway and the trans-sulphuration pathway.

For these pathways to function correctly key nutrients in the form of betaine, B6, B9 and B12 are necessary. When one or more of these nutrients are in short supply these homocysteine-lowering mechanisms are compromised. Therefore, ensuring that the body has an adequate supply of betaine, B6, B9, and B12 may have a very important role in reducing the risk of arthrosclerosis and subsequent cardiovascular problems.


  1. “McCully, K. (2007). Homocystine, vitamins, and vascular disease prevention. American Journal of Clinical Nutrition. Volume 86, Issue 5, (pp. 1563S-S8).”
  2. “Eikelboom, J. et al. (1999). Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Annuals of International Medicine. Volume 131, Issue 5, (pp. 363-75).”
  3. “Sunden S. et al. (1997). Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Archieves of Biochemistry and  Biophysics. Volume 345, Issue 1, (pp. 171–4).”
  4. “Pajares, M. and Perez-Sala, D. (2006). Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? Cellular and Molecular Life Sciences. Volume 63, Issue 23, (pp. 2792-803).”
  5. “Olthof, M. et al. (2003). Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. Journal of Nutrition. Volume 133, Issue 12, (pp. 4135-8).”
  6. “Steenge, G. et al. (2003). Betaine supplementation lowers plasma homocysteine in healthy men and women. Journal of Nutrition. Volume 133, Issue 5, (pp. 1291-5).”
  7. “Atkinson, W. et al. (2008). Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects. American Society for Clinical Nutrition. Volume 87, Issue 3, (pp. 577-85).”
  8. “Alfthan, G. et al. (2004). The effect of low doses of betaine on plasma homocysteine in healthy volunteers. The British Journal of Nutrition. Volume 92, Issue 4, (pp. 665-9).”
  9. “Olthof M. et al. (2005). Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PLoS Medicine. 2:e135.”