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Homocysteine as a Risk Factor for Disease

By Laura J. Ninger, ELS

October 2006

By Laura J. Ninger, ELS


Alzheimer’s Disease: Rising levels of homocysteine could be an early warning signal of impending dementia and Alzheimer’s in elderly men and women. High homocysteine (greater than 14 μmol/L) almost doubled the risk of Alzheimer’s disease, suggesting a possible cause-and-effect relationship between homocysteine and Alzhiemer’s.41

Cardiovascular Disease: High homocysteine levels make the cardiovascular risks of smoking even more dangerous. In one study, smokers with high homocysteine levels had 12 times the risk of cardiovascular disease compared to nonsmokers with normal homocysteine.42

Ischemic Heart Disease and Stroke: Lowering homocysteine levels may decrease the risk of heart disease and stroke.43-45 Studies have suggested that lowering one’s homocysteine level by 3 μmol/L could decrease the risk of ischemic heart disease by 11-16%, while decreasing the risk of stroke by 19-24%.43,44


Dementia: Because elevated homocysteine plays a role in stroke and Alzheimer’s disease—two major causes of dementia—researchers proposed that dietary supplementation to normalize homocysteine levels could reduce rates of dementia.46

Cognitive Impairment: Healthy people who wish to maintain their cognitive function should monitor their homocysteine levels. Over the course of six years, healthy individuals with high homocysteine levels at the study’s onset had much poorer scores on word-learning tests than their counterparts with low homocysteine levels.47

Inflammatory Bowel Disease: High levels of homocysteine in the colon and blood may predispose individuals to two inflammatory bowel diseases: ulcerative colitis and Crohn’s disease. Homocysteine levels were significantly elevated in the colons of patients with inflammatory bowel diseases compared to healthy subjects.48

Ischemic Heart Disease and Stroke: People with high homocysteine levels have a much greater risk of ischemic heart disease and stroke.49 In patients with coronary heart disease, those with the highest homocysteine levels had an almost fivefold greater risk of stroke.50 Some research suggests that lowering homocysteine by 25% may lead to an 11% decrease in ischemic heart disease risk and a 20% decrease in stroke risk.49


Aneurysm: One of the most dangerous manifestations of cardiovascular disease is aortic aneurysm, a bulging of the body’s largest artery that can lead to rupture, a potentially fatal surgical emergency. Researchers found that 68% of adults with abdominal aortic aneurysm had elevated homocysteine levels, compared to only 6% of unaffected individuals. Patients with aneurysm had an average homocysteine level of 19.4 μmol/L, compared to 10.9 μmol/L among unaffected adults.51

Cardiovascular Disease: About half of all deaths occur because of cardiovascular disease, and elevated homocysteine may contribute to 10% of cardiovascular disease cases and deaths.52 Cardiovascular disease risk grows as homocysteine increases, and the risk is especially high in people with high blood pressure, diabetes, or high lipid levels.52 Homocysteine damages blood vessels, promotes blood clotting, and generates oxidative stress.52 Some experts estimate that lowering homocysteine could prevent 25% of cardiovascular events,52 and some recommend that all individuals at risk for heart disease should be treated regardless of their baseline homocysteine values.53 Homocysteine poses risks to men, women, and children, and particularly to people with underlying illnesses.54-56

Cognitive Impairment: High levels of homocysteine are associated with detrimental changes in the nervous system that can be detected using radiological imaging57 or clinical assessments.58 In one study, people with the highest homocysteine levels had lower scores on cognitive function tests. High homocysteine levels were also associated with a 4.3 times higher risk of dementia and a 3.7 times greater risk of Alzheimer’s disease.58

Osteoporosis: Elevated homocysteine levels may increase the risk of osteoporotic fractures in older men and women.59,60 In one report, the risk of hip fracture increased with rising levels of homocysteine in both sexes.59 Men with the highest levels had about four times the risk of fracture as men with the lowest levels, and women with the highest values had twice the risk as those with the lowest levels.59 Lowering homocysteine levels using nutritional strategies may thus help protect bone health.59


Alzheimer’s Disease: Rising levels of homocysteine may predict impending cognitive decline and Alzheimer’s disease.61,62 In one study, high levels of homocysteine were associated with worse cognitive function, and elevated homocysteine predicted more severe cognitive decline during seven years of follow-up.61 Moreover, elevated homocysteine was associated with a three times higher risk of Alzheimer’s disease and a 2.6 times higher risk of mild cognitive impairment, which typically precedes more severe dementia.62

Aneurysm: People who have high homocysteine levels may have an eightfold greater risk of abdominal aortic aneurysm. When an aneurysm ruptures, fatal bleeding can occur unless the patient receives prompt surgical care.63

Atherosclerosis: Elevated homocysteine may speed the progression of atherosclerosis. One study showed that atherosclerosis progressed by 35% annually for patients with high homocysteine levels (greater than or equal to 12 μmol/L), but by only 17% per year in people with lower levels (less than 12 μmol/L).64

Cardiovascular Disease: When researchers followed healthy men for 10 years, they noticed that the men with the highest homocysteine levels had nearly twice the risk of cardiovascular disease death.65 Homocysteine was even more dangerous in smokers and in men with high cholesterol.65 In healthy women, increased homocysteine levels were associated with decreased oxygen uptake, indicating poorer cardiovascular fitness.66

Cognitive Impairment: Homocysteine may interfere with healthy mental function.67-69 In one report, healthy elderly people with high homocysteine levels experienced more dramatic cognitive decline over six years than did their counterparts with lower homocysteine levels.68 One study suggested that homocysteine may prematurely age the brain. A rise in homocysteine was equivalent to an extra 4.2 years of age on cognitive performance tests. Homocysteine might thus be a modifiable cause of cognitive decline.69

Depression: Depression and high homocysteine appear to be closely related. In people aged 60-64, a higher homocysteine level was associated with a higher prevalence of depression.70

Macular Degeneration: Homocysteine may damage eye health and threaten visual function. In fact, scientists found that patients with age-related macular degeneration had significantly higher homocysteine levels than healthy subjects.71,72

Bipolar Disorder: Homocysteine may be associated with bipolar (manic depressive) disorder. One study showed that young men with bipolar disorder had much higher homocysteine levels than healthy subjects, and homocysteine levels were highest in those with progression of the disease.73

Osteoporosis: Elevated homocysteine may adversely affect bone health and fracture risk.74 In healthy adults, high homocysteine was associated with 3.8 times the risk of fracture in men and 2.8 times the risk in women.75 Scientists believe that elevated homocysteine could be a clinical sign of osteoporosis related to nutritional deficiencies.74 High homocysteine may especially increase the risk of fractures in people suffering from underlying illnesses, such as Parkinson’s disease or a history of stroke.76,77

Schizophrenia: Some scientists believe that schizophrenia begins even before birth. Pregnant women with high levels of homocysteine were found to be more likely to have children who later developed schizophrenia. Researchers believe this may be one more reason why pregnant women should take steps to correct elevated homocysteine levels.78

Stroke: Over the course of 10 years, men with high homocysteine levels had nearly three times the risk of stroke as men with low levels of homocysteine. High serum folate levels, however, were associated with protection against stroke.79


Coronary Artery Disease: People with elevated levels of homocysteine were found to have more calcification of the coronary arteries than people with lower homocysteine values. Coronary artery calcification is a measure of the severity of coronary artery disease.80

Kidney Disease: Patients with chronic kidney disease were found to have significantly higher levels of homocysteine than healthy people. In fact, 89% of these patients had homocysteine levels greater than 14 μmol/L, which may increase their risk of developing many other diseases.81

Macular Degeneration: Patients with age-related macular degeneration, a common cause of visual loss, were found to have higher homocysteine levels than healthy subjects. Levels above 12 μmol/L particularly increased the risk of macular degeneration. High homocysteine level may thus be an independent risk factor for age-related macular degeneration.82

Osteoporosis: Women with high homocysteine levels were found to have significantly lower bone mineral density in the hip than control subjects. In fact, the risk of low bone density was 96% higher among women with high homocysteine (greater than 15 μmol/L) compared to women with lower homocysteine (less than 9 μmol/L). Homocysteine may be a modifiable risk factor for osteoporosis in women.83

Schizophrenia: Homocysteine levels are extremely high in many patients with schizophrenia. When these individuals used vitamins to decrease homocysteine, their symptoms of schizophrenia lessened.84


Elevated homocysteine levels have now been correlated with a wide array of illnesses, including heart disease, stroke, osteoporosis, depression, schizophrenia, macular degeneration, cervical cancer, and birth defects.

Fortunately, those seeking to safeguard their health and longevity can readily modulate elevated homocysteine levels using nutritional therapies such as vitamins B6 and B12, folic acid, and trimethylglycine.85 These important nutritional strategies may help you avert the wide array of diseases that have been found to accompany excessive levels of homocysteine.


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