Letters to the Editor
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The report in the September issue by Liu et al (1) concerning the Nurses' Health Study concluded that the strong inverse association between whole-grain intake and coronary heart disease was to a large degree not explained by the constituents of whole-grains thought to be protective. The accompanying editorial (2) essentially concluded the same.
One constituent and confounder not considered in this study, nor in most studies regarding coronary heart disease and homocysteine's potentially detrimental role therein, is betaine (trimethylglycine). Betaine, although once considered a vitamin-like component (3), is also endogenously synthesized from choline. It is found in whole grains and represents ~0.5% of wheat bran and wheat germ but only 0.06% (and often <0.02%) of white wheat flour. Choline, the endogenous betaine precursor, represents ~0.2%, 0.3%, and 0.08% of wheat bran, wheat germ, and white flour, respectively (3).
Betaine is the only non-vitamin-dependent homocysteine-lowering agent that methylates homocysteine to form methionine through a pathway that appears to be unhindered by any known genetic enzyme dysfunctions. Betaine is also considered a lipotrope, being related to lecithin and choline, and was used as suchin combination with B vitamins and liver extractin promising clinical coronary heart disease research done by Lester M Morrison in the 1950s (4, 5).
The almost general omission in research of betaine as a cardioprotective variable or as a confounder during the past 40 y or so is largely due to the absence of food tables that include betaine. In addition to whole grains, betaine is found in liver, eggs, and seafood. It is also found in plants such as beets and spinach, in which its role appears to be to increase resistance to drought and saline growing conditions.
The development of food tables that include betaine and its endogenous precursor choline is urgently needed to enable these confounders to be included in cardiovascular research and to close the gap of unrecognized confounders (1).