Choline Battles Homocysteine

Choline Battles Homocysteine
It helps prevent a host of ills (in the heart, the brain, and
elsewhere) spawned by this molecule of mayhem
By Will Block

ife is an ongoing molecular battle between the forces of Good and Evil. The bad guys in this drama strive to do us harm by causing disease, debilitation, and our untimely end. Living well and long takes a major effort on the part of the good guys, and it is our mission to help them in every way we can, because their foes are relentless.

Pathogens such as bacteria and viruses are like Special Forces—highly trained commandos who, even in small numbers, are capable of doing awesome damage in a very short time. Other substances, such as free radicals, are more like Barbarian hordes, laying waste to almost everything in their path through indiscriminate violence and overwhelming numbers.

There are many other categories of bad guys on the battlefield—mutant genes, oxidized lipoproteins, and advanced glycation end products (AGEs), to name a few—all of which take their toll on our health in their own insidious ways. And then there is the occasional Lone Wolf, a single compound that creates mayhem all by itself, with no need for help from its biochemical relatives.

A molecule that can fairly lay claim to being the worst of this breed is homocysteine. It’s an amino acid that is not an invader from outside, but a natural constituent of our bodies, a normal breakdown product of the essential amino acid methionine. Homocysteine and methionine coexist in a state of chemical equilibrium—an equilibrium that can be shifted in one direction or the other (i.e., toward more of one compound and less of the other) by a myriad of factors whose ever-changing spectrum is characteristic of the complexity of life processes.

Homocysteine Wreaks Age-Related Havoc

What makes homocysteine so dangerous to our health is not so much that it resides within us (we get it mainly from eating methionine-rich foods—notably meat, chicken, fish, and eggs), but that its levels in our blood tend to increase as we age. This occurs in both men and women, but typically to a greater degree in men, and it greatly increases our risk for atherosclerosis and heart disease, in particular.

Normally, homocysteine levels are kept under control through chemical conversion back to methionine or to another amino acid called homoserine. Various factors can impair the efficiency of these processes, however, especially as we age, so we must adopt effective countermeasures against rising homocysteine levels. As long as we do so, homocysteine poses no serious threat to our health. Besides, it serves useful purposes in our bodies, in the processes of cellular metabolism and protein synthesis (so it’s not all bad).

But what happens if we don’t put a lid on homocysteine? If you’re game for a nightmarish scenario, see the sidebar below. Meanwhile, let’s see what can be done about excessive homocysteine. Besides becoming vegetarians (not too popular, nor easy to stick to, but a very healthy lifestyle choice) and getting more exercise (ditto), there are at least two things we can do. One of them is well known because it has received much publicity in recent years, and the other one isn’t.

An Inventory of Homocysteine Horrors

Homocysteine is not an Attila the Hun type of molecule, wildly slashing and burning its way through your tissues to bring you to a quick and brutal end. Instead, homocysteine is more like Osama bin Laden, a patient monster lying low, plotting and scheming to do who knows what, who knows where, who knows when, with the possibility of devastating impact in the long run.

Following is a summary of the risks that are increased if our homocysteine levels are allowed to become too high. We’ll start with the one for which homocysteine is most notorious.

  • Neural tube defects – These are dreadful birth defects, such as spina bifida (an imperfectly closed spinal column) and anencephaly (the congenital absence of most of the brain and spinal cord). It’s vital that pregnant women keep their homocysteine levels down so as to minimize the risk for such tragedies.
  • Vascular disease – Elevated homocysteine levels are associated with a 2-to-40-fold increase in the risk for cardiovascular disease (including heart attack), cerebrovascular disease (including stroke), and peripheral vascular disease (including deep-vein thrombosis).1 Excess homocysteine is so harmful, in fact, that it is thought to be as important as cholesterol, if not more so, as a cause of atherosclerosis. It acts by promoting the formation of blood clots, by accelerating the oxidation of lipoproteins, and by damaging the endothelial cells that form the inner lining of our blood vessels, making them more vulnerable to the formation of atherosclerotic plaque (which often incorporates blood clots as well as oxidized lipoproteins and cholesterol).
  • Hypertension – Endothelial cells play a vital role in the expansion and contraction of our blood vessels—actions that are necessary to help regulate blood pressure. It is believed that excess homocysteine impairs the function of these cells via several different mechanisms and that, under some circumstances, it may even kill them.
  • Inhibition of angiogenesis – Angiogenesis is the formation of new blood vessels wherever they’re needed, such as for healing wounds and for restoring blood flow to tissues that have been injured in some way. It’s obviously a desirable process—except when it fosters the growth of tumors. In that case, homocysteine might be thought to be beneficial, but it is still apparently insufficient to protect against …
  • Cancer – High homocysteine levels are linked to an increased risk for several cancers, colorectal cancer in particular.
  • Neurodegenerative diseases – The risk for Alzheimer’s disease and Parkinson’s disease is increased by homocysteine, and there is evidence that this may also be true for Huntington’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease), epilepsy, and even schizophrenia. Homocysteine apparently has a propensity to damage and even kill neurons (nerve cells) by damaging DNA molecules.
  • Depression – Homocysteine is implicated in depression, yet another affliction that becomes more prevalent with age. There is a well established correlation between the two, and correcting the low levels of folate and vitamin B12 commonly found in depressed individuals alleviates the incidence and severity of depression.
  • Alcoholism – Alcoholics have very low folate and vitamin B12 levels, and it’s likely that the associated high homocysteine levels contribute to the various pathologies associated with alcohol, including liver disease and cognitive and motor dysfunctions.

In addition, excessive homocysteine is apparently linked with increased risks for type 2 diabetes, rheumatoid arthritis, osteoporosis, hypothyroidism, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), and more. If ever there was a molecule that needed to be beaten down in our bodies, homocysteine is the one!

  1. Beers MH, Berkow R, eds. The Merck Manual of Geriatrics, 3rd ed., p. 593. Merck Research Laboratories, Whitehouse Station, NJ, 2000.

Folic Acid Regulates Homocysteine, and . . .

The well known approach is to supplement our diets with the B-vitamin folic acid (also known as folate), together with its necessary cofactor, vitamin B12 (vitamin B6 is also helpful in this regard). Folic acid is highly effective in regulating homocysteine levels—provided that one gets enough of it. In 1998 an FDA mandate took effect that required all refined cereal grains in the United States to be fortified with folic acid in amounts intended to add about 100 mcg/day to the average diet (the RDA is 400 mcg); the actual increase turned out to be almost twice that amount—190 mcg/day—on average.1 Even so, folic acid deficiency is still probably the most common vitamin deficiency in this country, affecting about 10% of the population.2

A further problem is that, although the RDA of 400 mcg is deemed by the FDA to be adequate, it is, like virtually all such RDAs, a conservative amount that falls short of what some scientists believe is a more nearly optimal amount—in this case, about 1000 mcg, or 1 mg.3* The percentage of Americans ingesting more than that amount daily is estimated to be 11%, meaning that 89% of Americans are getting that amount or less—probably much less, in most cases.1

*In supplementing with folic acid, it’s essential to take additional vitamin B12 as well, because too much of either of these nutrients can mask a deficiency in the other; for all practical purposes, the two should be regarded as nutritionally inseparable. The amount of vitamin B12 recommended to accompany 1000 mcg of folic acid is 500 mcg.3 (For more detailed information on these recommendations, see “Fight Alzheimer’s and Heart Disease with B-Vitamins” in Life Enhancement, December 2001. And for more on folic acid, see “Folic Acid to the Rescue!” in the September 2002 issue.)

What can we do about this? We can take more supplemental folic acid, of course, and we can eat more of the foods that contain it—mainly whole grains, citrus fruits, green vegetables, and beans (but note that cooking can destroy folic acid). We can also avail ourselves of the other, relatively unknown approach to dealing with homocysteine: we can supplement with the nutrient choline (which is a nitrogenous alcohol).

. . . So Does Choline

Choline, as it turns out, also reduces homocysteine levels, albeit indirectly. When choline is ingested (the average daily intake from food is about 400–900 mg), some of it is converted to a nitrogenous acid called betaine, and betaine regulates homocysteine by converting it back to methionine, in a process called methylation.

A recent study at the University of North Carolina at Chapel Hill sought to determine how important this choline-induced process actually is.4 To do so, the researchers examined whether a dietary choline deficiency in mice and humans (in the latter case, 8 healthy men aged 20 to 46) was associated with increased homocysteine levels. If so, that would indicate that choline is a necessary ingredient in the body’s “recipe” for homocysteine regulation.

To prevent the results from being skewed by a possible deficiency of folic acid, the researchers made sure that folic acid and other B-vitamin levels were within the recommended range for adequate homocysteine regulation. Then they studied the effects of a severely choline-deficient diet, compared with a normal diet, on the responses of the two species to an artificially induced excess of homocysteine in the blood. The normal daily diet for the men contained 550 mg of choline per 70 kg (154 lb) of body weight, whereas the restricted diet contained less than 50 mg of choline per 70 kg of body weight.

Choline May Be as Important as Folic Acid

In this tale of mice and men (sorry, Steinbeck), the results showed that a deficiency of choline substantially impaired the body’s ability to regulate homocysteine levels. The authors concluded,

The present study shows that, among its other functions, choline may be important for lowering plasma homocysteine concentrations even when dietary consumption of folate and other B-vitamins is adequate. … Thus, in both mice and humans, we showed that, when homocysteine flux was high, folate-dependent methylation was limiting, and choline- betaine-dependent methylation became critical.

In other words, without adequate levels of choline, the supposedly adequate levels of folic acid and the B-vitamins are apparently insufficient for dealing with homocysteine “spikes,” such as can occur after eating methionine-rich foods. Adequate choline levels, however, can make up for the shortfall. What this tells us is that maintaining optimal levels of choline in our bodies may be as important for our health as maintaining optimal levels of folic acid, and we should pay close attention to both.

“The present study shows that, among
its other functions, choline may be
important for lowering plasma
homocysteine concentrations even
when dietary consumption of folate
and other B-vitamins is adequate.”

A Good Drinking Habit

Choline (good guy) and homocysteine (bad guy) have similar molecular structures—but only superficially. If the devil is in the details of homocysteine, then angels are in the details of choline. These details are responsible for the profoundly different chemical properties and physiological effects of these two molecules.
Paying attention to choline is a good idea for other reasons as well, most notably because choline is a precursor to several compounds of very great importance to the structure and function of the brain. That will be the subject of another article on choline coming next month in the pages of this magazine. Meanwhile, let us note that the principal dietary sources of choline, in decreasing order of concentration, are beef liver, chicken liver, eggs, wheat germ, bacon, dried soybeans, and pork.5

A more reliable way to obtain optimal amounts of choline, of course (especially for people who don’t like liver), is through supplementation. Unlike most supplements, which come in capsules, choline comes as a flavorful drink mix, and it’s particularly satisfying, when downing that drink, to know that you’re siccing a really Good Guy on the forces of Evil.


  1. Choumenkovitch SF, Selhub J, Wilson PWF, Rader JI, Rosenberg IH, Jacques PF. Folic acid intake from fortification in United States exceeds predictions. J Nutr 2002;132:2792-8.
  2. Mattson MP, Kruman II, Duan W. Folic acid and homocysteine in age- related disease. Ageing Res Rev 2002;1:95-111.
  3. Tice JA, Ross E, Coxson PG, Rosenberg I, Weinstein MC, Hunink MGM, Goldman PA, Williams L, Goldman L. Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease. JAMA 2001;286(8):936-43.
  4. da Costa KA, Gaffney CE, Fischer LM, Zeisel SH. Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load. Am J Clin Nutr 2005;81:440-4.
  5. Zeisel SH. Nutritional importance of choline for brain development. J Am Coll Nutr 2004;23(6):621S-626S.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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