Natural treatments for hyperhomocysteinemia

• PRINCIPAL PROPOSED NATURAL TREATMENTS: Folate, vitamin B₆, vitamin B₁₂
• OTHER PROPOSED NATURAL TREATMENTS: Phosphatidylcholine, trimethylglycine

DEFINITION: Treatment of abnormally high levels of homocysteine (over 15 micromol per liter of blood), a substance produced when the body breaks down the amino acid methionine.

Introduction

Beginning in the late 1990s, medical researchers began to suspect that high levels of homocysteine—a substance produced when the body breaks down the amino acid methionine using B vitamins—may accelerate atherosclerosis, the primary cause of heart attacks, strokes, and intermittent claudication. During a brief period, it was widely proclaimed that homocysteine was an even more important risk factor for heart disease than cholesterol. However, further research found conflicting results with homocysteine reduction providing minimal benefits. Though it remains an independent risk factor for several health conditions, hyperhomocysteinemia's treatments and diagnosis are controversial, and interprofessional research is needed to better understand the condition.

Most of the supporting evidence for a homocysteine-atherosclerosis connection comes from observational studies that found an association between high levels of homocysteine and increased atherosclerosis. Observational studies, however, do not show cause and effect. It is possible that unknown underlying factors increase homocysteine levels and also accelerate atherosclerosis rather than that high homocysteine causes accelerated atherosclerosis. Only intervention trials—studies in which groups of people are given a treatment or a placebo—can show whether a treatment is effective. Five massive studies of this type have been reported, involving more than eighteen thousand men and women. In these studies, high doses of supplementary vitamin B₆, vitamin B₁₂, and folate were used to lower homocysteine levels. None of these studies found significant benefits for preventing stroke, heart attack, or heart-related death.

A smaller study failed to find that these same homocysteine-lowering vitamins preserved mental function in people with the loss of mental function caused by atherosclerosis in the brain. Another study failed to find that lowering homocysteine with B vitamins can improve mental function in older adults. On one of the few positive notes, one substantial trial found that the use of these homocysteine-lowering nutrients helped prevent restenosisrecurrent vessel cloggingafter angioplasty. Similar studies found benefits for lowering homocysteine using medicinal plants and herbal bioactive compounds, but conclusive evidence remained out of grasp.

In addition to atherosclerosis, correlations have also been found between high homocysteine levels and numerous other diseases, including Alzheimer’s disease, coronary artery disease, osteoporosis, complications of pregnancy, deep venous thrombosis, and pulmonary embolism. The results of double-blind studies are mixed concerning these connections. One substantial double-blind, placebo-controlled study failed to find that reducing homocysteine levels can help prevent recurrent deep venous thrombosis or pulmonary embolism. Data gathered in another study also failed to show benefit for preventing these two conditions. Four double-blind studies failed to find benefit for Alzheimer’s disease or other forms of dementia. Additionally, double-blind studies of B vitamins for reducing osteoporosis risk have not produced convincing evidence of benefit. Conversely, a double-blind, placebo-controlled study in Denmark of 728 older adults with high homocysteine and relatively low folate intake found that the use of folate supplements slowed the progression of age-related hearing loss and may also improve mental function in older adults.

Another study found that in people who had already had a stroke and were partially paralyzed, supplementation with vitamin B₁₂ and folate reduced the risk of falls, leading to hip fractures. Participants were older Japanese people with high levels of homocysteine and low levels of folate and vitamin B₁₂. It is not clear how the treatment produced this benefit: it might have reduced the tendency for recurrent strokes or might have strengthened bones, improved balance, or produced benefit by some other means. Another study used blood tests to look at effects on bone but failed to find that reducing homocysteine levels had any effect.

People with diabetes or inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis, and those undergoing kidney dialysis may be at higher-than-normal risk for elevated homocysteine levels. A simple blood test can determine homocysteine levels. Both conventional and alternative practitioners use the natural substances described here to treat elevated homocysteine.

Principal Proposed Natural Treatments

Three nutrients act together to help the body reduce homocysteine levels: vitamin B₆, vitamin B₁₂, and folate. Many Americans are at least marginally deficient in vitamin B₆. Vitamin B₁₂ deficiency occurs primarily in older adults and people who take drugs that suppress stomach acid. Folate deficiency is thought to have become fairly uncommon in the US because of the enrichment of grains that began in the late 1990s. Though rare, some people can not process methionine due to a genetic condition called homocystinuria. However, the dose of folate required to achieve maximum homocysteine reduction is 800 micrograms daily, higher than the usual nutritional recommendations. Nonetheless, studies utilizing high doses of these vitamins for lowering homocysteine and, therefore, preventing cardiovascular disease have generally failed to find benefit.

Despite mixed research results, a review of the literature from the first two decades of the twenty-first century found some benefits for folic acid supplementation in patients with high homocysteine. Because the supplement is readily available and cost effective, the researchers recommended early intervention with folic acid supplementation to reduce the risk of vascular disease and other deleterious processes.

Other Proposed Natural Treatments

Some people develop extraordinarily high levels of homocysteine because of a genetic defect. The supplement trimethylglycine (TMG) is a treatment for this condition approved by the US Food and Drug Administration. TMG also seems to be effective for milder forms of high homocysteine. However, the nutrients mentioned in the foregoing section are less expensive and probably equally, if not more, effective at lowering homocysteine. Furthermore, TMG might raise cholesterol levels, thereby potentially undoing whatever benefit that might result from lowering homocysteine.

Phosphatidylcholine might also reduce homocysteine. Another study failed to find soy isoflavones helpful for reducing homocysteine levels.

Bibliography

Aisen, P. S., et al. “High-Dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease.” Journal of the American Medical Association, vol. 300, 2008, pp. 1774-83.

Albert, C. M., et al. “Effect of Folic Acid and B Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease.” Journal of the American Medical Association, vol. 299, 2008, pp. 2027-36.

Atazadegan, Mohammad A., et al. “The Effects of Medicinal Plants and Bioactive Natural Compounds on Homocysteine.” Molecules, vol. 26, no. 11, May 2021, p. 3081. doi:10.3390/molecules26113081.

Ebbing, M., et al. “Mortality and Cardiovascular Events in Patients Treated with Homocysteine-Lowering B Vitamins After Coronary Angiography.” Journal of the American Medical Association, vol. 300, 2008, pp. 795-804.

Kaye, Alan D., et al. “Folic Acid Supplementation in Patients with Elevated Homocysteine Levels.” Advances in Therapy, vol. 37, no. 10, 2020, pp. 4149-64. doi:10.1007/s12325-020-01474-z.

Son, Phillip, and Lindsay Lewis. "Hyperhomocysteinemia." StatPerals, National Library of Medicine, 8 May 2022, www.ncbi.nlm.nih.gov/books/NBK554408. Accessed 1 Oct. 2024.

Van Uffelen, J. G., et al. “The Effect of Walking and Vitamin B Supplementation on Quality of Life in Community-Dwelling Adults with Mild Cognitive Impairment.” Quality of Life Research, vol. 16, 2007, pp. 1137-46.