Homocysteine: The amino acid that predicts heart disease


I recently went for my annual physical, and for the first time ever, I had my homocysteine levels checked by my new doctor. They were within the normal range, but on the higher end, so we discussed ways to get my number a bit lower. She also explained what homocysteine is and what it means to my health. Some of it I already knew, but some of it really surprised me.

And some of it may surprise you too. So, here’s a little primer on homocysteine that you might find helpful. Here’s what you need to know…

What Is Homocysteine?

Homocysteine is an amino acid produced in the body when you eat protein. It is an “intermediate product” created during the metabolism of the amino acids methionine and cysteine.

You need some homocysteine in your system because it breaks down into useful compounds involved in energy metabolism. Any excess homocysteine, however, is broken down by B vitamins. If you’re low or deficient in the B vitamins, it hinders this cycle, which can lead to accumulated homocysteine over time.

Other possible causes of elevated homocysteine include low thyroid hormones, kidney disease, certain medications, and a variant of the MTHFR gene called C677T. MTHRF is involved in the production of an enzyme necessary for metabolizing folate (vitamin B9). People with the C677T variant have a hard time breaking down homocysteine due to the lack of folate. If your homocysteine levels are extremely high, your doctor may want to test you for this variant.

Homocysteine and Heart Health

When it comes to heart health, cholesterol and inflammation may be the most talked about risk factors. But homocysteine should really get more attention because it’s also a big predictor of heart disease. Increased levels are linked to atherosclerosis, blood clots, and stroke.

One study, looking at two large population groups (Multi-Ethnic Study of Atherosclerosis, or MESA, and National Health and Nutrition Examination Survey III, or NHANESIII) examined homocysteine’s effect on risk of cardiovascular disease. The researchers found that homocysteine levels above 15 μmol/l significantly predicted cardiovascular disease and events in the MESA group, and cardiovascular events and mortality in the NHANESIII group.

When added to existing Framingham Risk Scores (this is a calculation that estimates 10-year risk of a heart attack), homocysteine reclassified (and increased) heart risk for 12 to nearly 20 percent of the people in the various intermediate risk groups. Researchers concluded that the addition of homocysteine to the Framingham Risk Score “significantly improved risk prediction, especially in individuals at intermediate risk…”

Homocysteine and Neurodegenerative Disease

Though homocysteine is most closely linked to heart problems, research also shows that high levels of this amino acid can contribute to neurodegenerative diseases including Alzheimer’s, Parkinson’s, vascular dementia, cognitive impairment, epilepsy, and autism.

A study out of Temple University recently revealed the extent to which elevated homocysteine can damage the brain.

Researchers already knew that homocysteine affected memory and promoted the formation of harmful amyloid plaques in the brain—one of the hallmarks of Alzheimer’s. But in this study, they discovered that excessive homocysteine also contributed to the development of damaging tau neurofibrillary tangles. These tangles lead to nerve cell death and a slew of neurodegenerative disorders such as dementia.

In their study, the researchers fed mice vitamin B-deficient diets to raise homocysteine. The mice were specially bred to develop tau tangles—but not amyloid plaques. This allowed the researchers to determine the effect of homocysteine on tau only.

Compared to the controls, these mice performed significantly worse on memory tests. They also had major trouble learning new tasks and remembering old tasks. Upon further examination, the brains of those test mice had 50 percent more dangerous tau tangles than the controls.

How to Lower Homocysteine

Too much homocysteine is problematic—that much is clear.

There’s some debate over what constitutes a “high” level, but most experts agree that a reading above 10-12 μmol/l needs to be addressed. The larger the number, the greater the risk.

Fortunately, the solution for reducing homocysteine is simple and inexpensive: Supplementation with B vitamins, specifically B6, B12, and folate.

According to one study: “Recent B vitamin supplementation trials demonstrated a slowing of brain atrophy and improvement in some domains of cognitive function. Meta-analysis of secondary prevention trials showed that B vitamins supplementation caused a decrease in plasma [homocysteine] and a trend for lowering the risk of stroke.”2

Even though small amounts of B vitamins are in most multivitamins, reducing homocysteine requires taking a specially formulated supplement consisting of methylated B9 (folate), B6, and B12.

Folate is important because it converts homocysteine into the harmless substance methionine. Make sure your supplement contains 400-800 mcg of folic acid. (Folic acid is simply the name given to the synthetic form of folate used in vitamins.) You should also increase your intake of folate-rich foods—leafy greens, egg yolk, wheat germ, lentils, and beef liver are some good ones.

B6 has been shown to protect against inflammation and can have wide ranging benefits if you suffer from an inflammatory condition, such as arthritis, gastritis, and other ailments ending in “-itis” (which literally means “inflamed”).

Make sure your supplement contains 15-25 mg of B6. In addition, eating more pinto beans, legumes, potatoes, red peppers, fish, hamburger, and lean chicken breast, are all good ways to increase your vitamin B6.

Vitamin B12 is crucial for energy production and support of the nervous system and cognitive function. To make an impact on homocysteine, take up to 1,000 mcg per day.

If you want to lower your homocysteine—and especially if you have the genetic MTHRF variant I mentioned earlier—adding these to your daily regimen can go a long way in ensuring better heart and brain health in the future.


Last Updated: November 20, 2019
Originally Published: September 26, 2019