Antioxidant Vitamins Block Homocysteine's Acute Toxic Effects

Antioxidant Vitamins Block
Homocysteine's Acute Toxic Effects

This section is compiled by Frank M. Painter, D.C.
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From the December 2000 Nutrition Science News

Richard N. Podell, M.D.

About one-fourth of all American adults have excessively high blood levels of homocysteine. This amino acid is formed from methionine, which is taken into the body via animal-derived foods. High levels of homocysteine translate into a significant increase in hardening of the arteries known as arteriosclerosis. In that way, homocysteine is similar to cholesterol because prolonged, elevated levels of it gradually damage the inner linings of blood vessels, causing atherosclerotic plaque and narrowing of the arteries. However, for a catastrophic end result of this process to occur — a heart attack or a stroke — it typically takes more than just narrow arteries: It requires the blood within the artery to congeal into a clot, suddenly causing an obstruction.

What generally triggers clot formation are things like smoking a cigarette, acute emotional stress, physical overexertion, a virus or even just getting out of the bed too quickly in the morning. Each of these factors, in their own way, can act within minutes to recast arterial blood into a hyper-coagulable state. Then, for the next minutes, hours or days the blood remains prone to clotting. Recently, researchers discovered that high homocysteine levels also function as such a trigger, producing a double whammy in that it creates the problem, then induces the final outcome. However, certain nutritional supplements seem to be effective at overcoming this danger.

After the body experiences a trigger, the critical period of high vulnerability to clotting is extremely influential. The body immediately works to return the blood's stickiness to normal. Therefore, if one can get through this high-risk period, within hours or days, blood viscosity can revert to normal. Progression to a heart attack or stroke usually is not inevitable; in fact, it can be avoided for years or even decades.

This month I examine a study that demonstrates how high homocysteine levels can cause dangerous, "sticky" blood and how a timely dose of vitamins C and E can almost completely prevent such effects.

Researchers at the Department of Geriatrics, Second University in Naples, Italy, examined homocysteine's effects on 10 healthy young men and 10 healthy young women. The subjects were each given three loads in random order at one-week intervals of 100 mg/kg oral methionine in fruit juice, the same methionine dose immediately after taking 1,000 mg ascorbic acid (vitamin C) and 800 IU vitamin E, and a methionine-free fruit juice placebo. Since the body normally converts methionine into homocysteine and vice versa, loading up on methionine was expected to cause homocysteine levels to rise. In this case, the methionine-only group experienced a homocysteine increase nearly three-fold — from an average of 10.5 umol/L at baseline to 27.1 umol/L — all within four hours.

At the same time, there was a marked increase in the blood levels of several biochemicals that increase blood's tendency to clot. This showed that using a loading dose of homocysteine precursor (i.e., methionine) caused a major increase in blood stickiness. For a high-risk person who has been walking around with moderate or severe arteriosclerosis, this increase in homocysteine could be enough to trigger a heart attack.

The good news is that when researchers added the 1,000 mg of vitamin C and 800 IU of vitamin E along with the methionine load, homocysteine's pro-blood-clot effects were almost completely prevented. That is, the blood clotting parameters remained normal despite a drastic increase in blood homocysteine levels.

It appears that the combination of vitamins C and E may be an antidote to homocysteine, and one that works more quickly than traditional treatments such as vitamins B6, B12 and folic acid. These vitamins can lower homocysteine levels over the course of a few weeks. In contrast, vitamins C and E can act within hours. While they don't actually reduce homocysteine, these vitamins appear to protect the blood from clotting.

This study has a few important practical implications for people at risk for heart disease or stroke, although additional studies must be done to further support these findings.

First, increasing homocysteine by overloading on protein foods or methionine-containing high-protein supplements can be dangerous.

Second, adding the antioxidant vitamins C and E as well as homocysteine-lowering B6, B12 and folate should help keep blood thin. By thinning the blood, it appears as though vitamins C and E might reduce the threat of other acute proclotting triggers such as smoking, exertion, a high-fat meal or emotional distress. However, while these two nutrients may protect against high homocysteine levels for a few hours, the duration of their protective effect is unknown. Considering vitamin E is stored in fat, a single dose should be available in the body for days, depending on how fast the vitamin is metabolized. However, vitamin C dissolves in water and is excreted in the urine. Thus, for those at risk, I'd urge a 1 to 2 g twice daily vitamin C dose.

Richard N. Podell, M.D., M.P.H., is director of the Podell Medical Center in New Providence, N.J.


1. Nappo F. Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA 1999;281:2113-8.

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