Homocysteine and Brain Health

Beware Homocysteine—Potent Brain Toxin

An amino acid in your blood that few doctors even knew about until very recently is now considered a major factor in brain breakdown. It’s called homocysteine, and too much of it can accumulate in blood, helping clog and destroy blood vessels, including those that feed the brain; it may even damage mental acuity and mood by a direct toxic effect on brain cells. Luckily, homocysteine is a dragon easily slain by modest doses of B vitamins, which makes its continuing human destruction all the more appalling. High homocysteine, like high cholesterol, can be determined by a blood test.

Unquestionably, high homocysteine is incriminated in failing intellectual abilities. Tufts University researchers recently reported that middle-aged to elderly men with the highest homocysteine blood concentrations performed on one test of mental competence exactly like patients with mild Alzheimer’s disease! In fact, among the 25 percent with the highest homocysteine, only 22 percent could cor­rectly copy a cube and only 17 percent could copy a tapered box. About 75 percent of those with the lowest homocys­teine levels drew the figures correctly, as can most chil­dren by age thirteen. Such subnormal performances in older people indicate the brain has been damaged, said researchers.

BRAIN ALERT: As much as 40 percent of cere­brovascular disease appears tied to high homocys­teine levels.

High levels of homocysteine signify not only problems with memory, concentration, and thinking abilities, but also to low moods. Among a group of depressed persons, young and old, the higher the homocysteine, the lower the scores on mental acuity and mood assessment tests. In a recent study of outpatients with major depression, 20 per­cent had elevated homocysteine and 19 percent, low folic acid.

BOTTOM LINE: High blood levels of homocysteine pre­dict increased susceptibility to mental impairment and depression in both the old and young.


Overwhelming evidence shows that high blood homocys­teine predicts strokes. A 1992 review of medical research (a meta-analysis) by Swedish researchers found that fully one-quarter of patients with cerebrovascular disease had high homocysteine. Angiograms of the carotid (neck) artery that feeds blood and oxygen to the brain revealed a blockage or closing in fully 85 percent of a group of patients with high homocysteine who had suffered a TIA (a prelude to stroke) or a minor stroke. In fact, homocys­teine is a stronger predictor of stroke than smoking, high blood pressure, or high cholesterol, revealed a large scale study of stroke victims by Swedish neurologist Dr. Lars E. Brattstrom at University Hospital in Lund. Forty percent who had strokes of all types—from an embolism, hemor­rhage, blockage, or carotid artery disease—had high homocysteine.

Similarly, British researchers studying 7,735 middle-aged men over a thirteen-year period found that the higher the homocysteine, the higher the stroke risk—regardless of weight, diabetes, cholesterol, high blood pressure, or smok­ing! Indeed, those with the highest homocysteine were about three times more apt to have a stroke than those with the lowest levels.


Also disturbing, high homocysteine is a sign you may be on the fast track for Alzheimer’s. A new study by Robert Clarke, M.D., of Oxford University in England, found that a high homocysteine reading raised odds of developing Alzheimer’s by an astounding 450 percent! Not surprisingly, those with Alzheimer’s also had low blood levels of folic acid and vita­min B12, which suppresses homocysteine. Low levels of folic acid tripled the odds of Alzheimer’s.

Even more alarming, the higher the blood homocysteine, the faster Alzheimer’s moved to destroy the brain. Homo­cysteine’s power to speed brain deterioration was seen on brain scans and on declining scores on mental and memory tests. Researchers visually charted the wasting away of spe­cific temporal lobes of the Alzheimer’s-diseased brains, and the higher the homocysteine, the greater the shrinkage. In those with the highest homocysteine, a specific brain lobe shrank about 20 percent in three years compared with only 5 percent in those with the lowest homocysteine. As expected, the progression of Alzheimer’s also was greatest in those with the lowest folic acid and B12.

How homocysteine promotes Alzheimer’s disease is not clearly understood, although recent evidence suggests the combination of disease in cerebral blood vessels and Alz­heimer’s interacts to worsen the brain damage. Further, high homocysteine may be a marker for low folic acid, thought to help protect the brain from Alzheimer’s.

BRAIN ALERT: High homocysteine triples your risk of stroke and quadruples your chances of Alzheimer’s disease.


The cure for brain-damaging homocysteine is amazingly simple and inexpensive: B vitamins, notably folic acid. The absence of folic acid allows toxic homocysteine to pile up wildly in the blood. Folic acid breaks it down. Vitamins B6 and B12 also help dispose of homocysteine, but folic acid is by far the most powerful suppresser. Harvard investigators determined that at least two-thirds of high homocysteine is linked to low levels of folic acid. People who take multi­vitamins, typically containing 400 micrograms of folic acid, have much lower homocysteine than nonvitamin users.

Taking B vitamins can even stop and reverse homocys­teine’s purported damage to vital carotid arteries, according to a groundbreaking 1998 study by Canadian cardiologist J. David Spence, M.D., at the University of Toronto. He and colleagues measured the progressive closure and plaque buildup in the carotid neck arteries of thirty-eight men and women, average age fifty-eight, before and after taking B vitamins for four and a half years. The results were aston­ishing.

When not taking B vitamins, the subjects’ plaque area increased about 50 percent. After taking vitamins, the plaque actually decreased in size about 10 percent. In short, the vitamins acted as a kind of detergent to clean out arter­ies and reverse atherosclerosis. Dr. Spence’s study used a high dose of folic acid-2.5 milligrams—because a few peo­ple need that much to overcome a genetic predisposition to extra high homocysteine. However, he says 400 micro­grams of folic acid—a typical daily dose—curbs high homo­cysteine in most people. He also gave 250 micrograms B12 and 25 milligrams of B6.

Why is high homocysteine a villain in blood vessel and brain tissue damage? One theory: Homocysteine sets the stage in blood vessel linings for clotting and deposition of plaque, leading to damage and closure of vessels. In par­ticular, homocysteine incites artery cells to synthesize col­lagen, a major component in atherosclerotic plaques, which may also cause stiffening of the blood vessel. Second, homo­cysteine may block the synthesis of neurotransmitters, such as serotonin. Third, high homocysteine may act as a neu­rotoxin by triggering metabolic changes resulting in acti­vation of substances, such as glutamate, that directly injure and kill brain cells.

BRAIN ALERT: Only one in ten Americans gets the amount of folic acid needed to curb high homocys­teine, according to Harvard researchers.

Alzheimer, Alzheimer's disease, Homocysteine, Folic acid, Stroke, mild alzheimer, high cholesterol, major depression,


Ironically, public health warnings against eggs, because of their high cholesterol, may actually aggravate the homo­cysteine problem. Egg yolks are one of the best sources of choline, a B vitamin. Studies in the 1950s showed that depriving animals of choline caused homocysteine levels to soar. Thus, shunning eggs in attempts to avoid heart dis­ease may in fact have worsened the risk by promoting high homocysteine levels. As it turns out, dietary cholesterol, as in eggs, is not a primary culprit in raising blood choles­terol.


  • Take folic acid, B6, and B12 supplements. Experts generally advise 400 micrograms of folic acid a day to squelch homocysteine. Dutch investiga­tors recently found that 250 micrograms of folic acid lowered homocysteine by 11 percent in younger women, and 500 micrograms reduced it by 22 percent. It worked best against the high­est levels of homocysteine. Another large study found that people taking multiple vitamins with 400 micrograms of folic acid had 10 to 15 per­cent lower homocysteine than non-vitamin­takers. A few people with genetic factors may need higher doses, prescribed by a doctor. Most experts say 25 milligrams of B6 and 250 micro­grams of B12 are generally enough to suppress homocysteine.
  • To keep a lid on homocysteine, you must con­tinue to take B vitamins. Stopping causes homo­cysteine to shoot up to abnormal levels again within four months or so.
  • Eat foods high in folic acid, such as orange juice, legumes, green leafy vegetables, almonds, forti­fied cereals, and avocados. However, your body utilizes only half as much folic acid from food as from supplements. A recent study found that eating high folic acid foods alone did not ade­quately suppress high homocysteine in about two-thirds of a group of elderly subjects. Thus, folic acid supplements are essential.
  • Restrict coffee to less than five cups daily. Recent Norwegian research found that homocysteine was 20 percent higher in people who drank more than nine cups of coffee compared with less than one cup daily. More than five cups daily may raise homocysteine, research suggests. Those who both smoked and drank lots of coffee had particularly high homocysteine.
  • Go easy on meat. The body makes homocysteine from high protein foods, notably animal protein, explains Kilmer S. McCully, M.D., at the Veter­ans Affairs Medical Center in Providence and originator of the homocysteine theory. Protein-rich plant foods are okay because they usually contain enough B vitamins to curb homocys­teine, he adds.
  • *Don’t smoke. Smoking suppresses folic acid lev­els, paving the way for excessive formation of homocysteine.

Jean-Paul Marat

Many tips are based on recent research, while others were known in ancient times. But they have all been proven to be effective. So keep this website close at hand and make the advice it offers a part of your daily life.

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