Homocysteine is a naturally occurring by-product of the breakdown of the essential amino acid methionine in the body. It represents a crucial intermediate step in the chemical conversion (demethylation) of methionine to another amino acid called cysteine. However, sustained elevated levels of homocysteine can be as dangerous as speeding without a seatbelt, posing significant risks to your health. This elevated homocysteine level is a major threat to your circulatory system, significantly increasing the risk of atherosclerosis —a condition where the arteries clog up, often leading to heart attacks and strokes.
Homocysteine is a naturally occurring by-product of the breakdown of the essential amino acid methionine in the body. It represents a crucial intermediate step in the chemical conversion (demethylation) of methionine to another amino acid called cysteine. However, sustained elevated levels of homocysteine can be as dangerous as speeding without a seatbelt, posing significant risks to your health. This elevated homocysteine level is a major threat to your circulatory system, significantly increasing the risk of atherosclerosis —a condition where the arteries clog up, often leading to heart attacks and strokes.
You may not realize that homocysteine is an amino acid vital to the metabolism of sulfur. This was first discovered by American biochemist Vincent Du Vigneaud in 1932. He found that homocysteine has one more carbon atom than cysteine, itself a vital component of all proteins. Du Vigneaud named it “homocysteine” because “homo” means “the same” in Greek.
In 1810, English chemist William Hyde Wollaston discovered an amino acid called “cystic” oxide after isolating it from bladder stones (the word “kystis” means bladder in Greek). Du Vigneaud later found that homocysteine played a key role in supporting healthy growth in animals deficient in methionine through a chemical transformation known as “trans-methylation.”
It wasn’t until 1962 that the true significance of homocysteine in human health and disease began to emerge. That year, cases of a new disease called homocystinuria were identified in children with mental retardation, dislocated ocular lenses, accelerated growth, osteoporosis, and a tendency to form blood clots in their arteries and veins.
In 1968, Dr. Kilmer McCully, then Head of the Pathology and Laboratory Medicine Service at the West Roxbury Veterans Affairs Medical Center in America, became interested in the connection between homocysteine and arteriosclerosis. He was inspired by a 1933 case of homocystinuria found by pediatricians at Massachusetts General Hospital.
Dr. McCully reviewed a case involving a 9-year-old girl with mental retardation, dislocated lenses, and abnormal blood vessels of the skin. The girl’s uncle, diagnosed in 1965 by the new Amino Acid Laboratory, had died of thrombosis of the carotid artery and a massive stroke. The pathologist noted that the uncle’s arteries were narrowed by arteriosclerosis—resembling changes usually found in a much older person.
Dr. McCully was one of the first research doctors to become intensely interested in amino acid metabolism. He studied the biochemistry of methionine and homocysteine at the National Institutes of Health in the USA, devouring all the pertinent literature on homocystinuria. His research confirmed the presence of arteriosclerosis in slides from the 1933 case and found arterial plaques scattered through the boy’s arteries.
Dr. McCully once studied the case of a 2-month-old baby boy who had recently died of a disease called Cobalamin C, characterized by the excretion of homocysteine, cystathionine, and methylmalonic acid in the urine. He saw a possible connection between homocysteine and arteriosclerosis. Upon restudying this case, he discovered surprisingly advanced arteriosclerosis, concluding that homocysteine directly caused arteriosclerosis (plaque buildup in the arteries) in these children.
Interestingly, no fats were found deposited in these children’s arteries, nor was cholesterol found in their arterial plaques. This indicated that homocysteine causes a unique pathology as it elevates and cannot be efficiently metabolized through trans-methylation.
In animal experiments, Dr. McCully’s research group found that administering pure homocysteine to rabbits led to arterial plaques and thrombosis. However, giving the animals pyridoxine (vitamin B6) simultaneously prevented arterial plaqueing and thrombosis. This was a fascinating discovery!
In Japan, Fumio Kuzuya repeated Dr. McCully’s experiments in the late 1970s, finding similar results and reporting them in Japanese articles. These findings were also mirrored by researchers Harker and Ross in Seattle, who used intravenous administration of homocysteine in monkeys.
These earlier animal experiments, while now viewed as cruel, were crucial in establishing the link between nutrition—or the lack of it—and the development of the homocysteine theory of arteriosclerosis in 1975. This theory helped explain several previous observations of experimental plaques in monkeys deprived of vitamin B6 and other methyl-donor nutrients such as Vitamins B2, B12, betaine, and folic acid.
Because B vitamins such as folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12) are all involved in normal metabolism that prevents excessive production of homocysteine, the homocysteine theory of arteriosclerosis implicated deficiencies of these vitamins in human arteriosclerosis, heart attacks, strokes, and amputations from vascular disease.
Dr. McCully’s groundbreaking work led to many more studies validating the link between dietary deficiencies and atherosclerosis. Folic acid is one of the most easily damaged and deficient vitamins in the world today, and heart disease remains a leading cause of death. It’s becoming increasingly clear that nutrient depletion plays a significant role in the growing incidence of heart and vascular disease.
Traditional food processing methods—such as the milling of grains, canning of foods, extraction of sugars and oils, and the addition of chemical additives—destroy sensitive vitamins like folic acid and vitamin B6. This depletion contributes to the rising rates of heart and vascular disease in the 21st century. On the flip side, the decline in cardiovascular disease mortality since the 1950s can be largely attributed to the fortification of processed foods with synthetic B vitamins.
The famous Framingham Heart Study provided crucial support for the homocysteine theory, showing that B vitamin deficiencies are widespread in older people, leading to elevated homocysteine levels and increased risk of arterial plaques.
In 1941, the US Government mandated the addition of B vitamins niacin (B3), thiamin (B1), riboflavin (B2), and iron to refined grain foods. By 1998, the role of folic acid in heart disease prevention had become so evident that the US Food and Drug Administration (FDA) mandated its addition to refined flour, rice, and other grain foods.
Despite hundreds of studies proving that elevated homocysteine levels increase the risk of heart disease, stroke, peripheral vascular disease, and reduced longevity, mainstream medicine still largely ignores the homocysteine threat, citing a “lack of clinical evidence.” As one doctor recently told me, the idea is “unproven” and “old hat.”
Too many older adults die from strokes each year. A study by the Centers for Disease Control and Prevention (CDC) in Atlanta found that the declining incidence of stroke mortality accelerated in 1998 in the US, but no change was found in the United Kingdom, where folic acid fortification isn’t mandated. A 2007 meta-analysis published in *The Lancet* concluded that trials reducing blood homocysteine levels through folic acid, pyridoxine, and cobalamin (Vitamin B12) over 3 to 5 years significantly reduced stroke mortality.
Interestingly, while the FDA recognizes folic acid’s role in preventing neural tube defects in the unborn, it hasn’t taken the same stance regarding folic acid, homocysteine, and heart disease prevention. This could be due to the potential impact on the lucrative cardiovascular pharmaceutical drug industry.
Adding folic acid to food was partly justified by its role in preventing neural tube defects. However, another rationale, not officially cited by the FDA, was the hope that folic acid fortification might also prevent vascular disease. Studies have shown that birth defects have decreased by about 19% in the US and up to 78% in Newfoundland, Canada, since folic acid fortification.
However, trials involving participants with a history of advanced vascular disease, heart attack, and stroke have been less successful. The Swiss Heart Study found that B vitamins benefited restenosis following coronary angioplasty, but a later trial with stented patients showed no benefit.
– Direct damage to the lining of blood vessels, weakening them and allowing plaque accumulation.
– Thrombogenic properties (triggering blood clots).
– Promotes the oxidation of LDL (“bad”) cholesterol, leading to plaque development on blood vessel walls.
– Increased susceptibility to free radical oxidative damage, potentially accelerating immune system deterioration.
– Sustained high homocysteine levels can lead to chronic diseases such as heart disease, Parkinson’s, Alzheimer’s, non-insulin-dependent diabetes, rheumatoid arthritis, pregnancy complications, MS, schizophrenia, depression, neural tube defects, and stroke.
– A minimum of 13,500 deaths from coronary artery disease in the US could be prevented annually by increasing folate intake to reduce homocysteine levels (JAMA, 1996).
Several factors can contribute to elevated homocysteine levels:
– Lifestyle Choices: Poor diet, excessive alcohol consumption, smoking, obesity, and inactivity.
– Nutrient Deficiencies: Particularly in folic acid, vitamins B12, B6, and betaine.
– Pharmaceuticals: The drug Methotrexate can increase homocysteine levels unless sufficient folic acid is taken. Methotrexate depletes folic acid, which normally helps lower homocysteine. Patients on this drug should routinely check their homocysteine levels.
– Genetic Factors: Some individuals are genetically predisposed to higher homocysteine levels.
– Stress: A major factor in my professional opinion. I’ve observed elevated homocysteine levels in many stressed-out corporate patients. Remember, no job is worth risking your health. If your levels are high and you’re dealing with stress, regular relaxation is crucial.
There are several risk factors associated with elevated homocysteine:
– High Alcohol Intake: Increases homocysteine.
– Excessive Coffee Consumption: Drinking six or more cups of coffee daily can raise levels.
– Smoking: Cigarette smoking is linked to higher homocysteine, especially when combined with coffee.
– Gender and Age: Men generally have higher homocysteine levels, and in women, levels increase post-menopause.
– Vegetarian Diets: Almost 30% of vegetarians have elevated homocysteine due to the relative lack of methionine and vitamin B12 in their diets.
– Genetics: Some people are genetically more likely to have higher homocysteine levels.
If you’re concerned about your homocysteine levels, ask your healthcare provider for a fasting blood test. It’s also wise to check your fasting cholesterol and blood pressure simultaneously. If all three are elevated, it’s time to take action.
The standard reference range for homocysteine levels can vary between labs and countries. Generally, for optimal cardiovascular health, you should aim for blood levels under 6-7 micromoles per liter. Studies suggest that levels above 6 micromoles per liter may increase the risk of heart attacks. In New Zealand, patients with cardiovascular disease are advised to keep their levels below 10 micromoles per liter.
Studies have shown that in countries with low cardiovascular disease mortality rates, like Japan, France, and Spain, homocysteine levels are typically around 7-8 micromoles per liter. In contrast, countries with higher mortality rates, such as Finland, Scotland, and Germany, have levels around 10-11 micromoles per liter. Here’s a proposed reference range based on age and gender:
| Age | Gender | Total Plasma (blood) homocysteine reference range |
| under 30 years | Male and Female | 4.6 – 8.1 µmol/L |
| 30 – 59years | Female | 4.5 – 7.9 µmol/L |
| 30 – 59 years | Male | 6.3 – 11.2 µmol/L |
| > 60 years | Male and Female | 5.8 – 11.9 µmol/L |
To lower your homocysteine levels and reduce associated risks, consider these steps:
1. Lifestyle Changes: Address the controllable risk factors.
2. Nutritional Supplementation: Work with a naturopath or a nutritionally oriented GP to identify any deficiencies. Supplements like Solgar’s Homocysteine Modulators can be beneficial.
3. Dietary Improvements: Enhance your diet to boost the intake of critical nutrients.
4. Regular Monitoring: Recheck your blood levels in 3 to 6 months to ensure they’re decreasing with treatment.
Article last update: 22 June 2011