Protect yourself against elevated homocysteine levels

Homocysteine is a toxic amino acid. It is normally present in the body as it is produced in several metabolic pathways. The transfer of methyl groups (CH3) from methionine is essential for the production of nucleic acids, fats and high-energy bonds. When methionine looses a methyl group, homocysteine is produced. This process is reversible and methylation is also responsible for the conversion of homocysteine to useful methionine and SAMe. If homocysteine levels increase, blood vessels are damaged and collagen formation is impeded. There are two pathways in the human body that can lead to the elimination of homocysteine. Homocysteine can be methylated to methionine or it can be condensed into cysteine.

Methylation is a metabolic process that involves the addition of methyl groups. The transmethylation of homocysteine into methionine requires methyltetrahydrofolate (the active form of folate) and vitamin B12.

In the transsulfuration pathway, the condensation of serine to homocysteine leads to the production of cysteine. This pathway is vitamin B6 dependant. Supplementation with vitamin B6 reduces homocysteine by a different mechanism than the one folic acid activates.

Why is Homocysteine harmful?
Homocysteine is an amino acid and elevated blood levels (Hyperhomocysteinemia) have been associated with higher incidences of coronary artery disease and increased risk of mortality from cardiovascular diseases. Hyperhomocysteinemia is an independent factor for peripheral vascular, cerebrovascular and coronary heart disease. High homocysteine levels have a variety of injurious effects on endothelial and smooth muscle cells and are thought to damage blood vessel walls and lead to complications such as premature occlusive arterial disease. Impairment in the methylation of homocysteine to cysteine might also lead to higher blood cholesterol levels because cysteine is required for the metabolism of cholesterol. It is also possible that the amino acid affects blood coagulation.

What causes elevated homocysteine levels?
Elevations can arise from multiple causes. Genetic defects leading to deficiencies of the enzymes required for the metabolism of homocysteine play a major role in inadequate homocysteine removal. However, severe hyperhomocysteinemia is usually caused by genetic defects or renal failure. Several different defects can impair the uptake, transfer, and conversion of dietary vitamin B12 into the active form of the vitamin. Defects in the enzyme 5-methyltetrahydro-folate-homocystinuria are the most common form of hyperhomocysteinemia. More than 20 mutations for the gene responsible for the production of the enzyme have been identified, with some responding to vitamin B6 supplementation while others do not.

Poor consumption of nutritional factors involved in homocysteine metabolism also lead to hyperhomocysteinemia; of particular importance are vitamins B12, B6 and folic acid. Insufficient intake of folate, vitamin B12 and B6 are common in the elderly. Low folate levels we shown to contribute to persistent elevations in homocysteine levels.

Research
• A study of over 1000 people showed that, as dietary folate intake decrease, homocysteine levels and stenosis of the carotid arteries increase. Similar results have been obtained for coronary artery stenosis, heart attacks and death due to cardiac disease.
• Hyperhomocysteinemia is believed to cause 60% of peripheral vascular disease
• The possibility that heart disease increases homocysteine levels has been ruled out by the Physician’s Health Study. The study showed that men with higher homocysteine levels had a threefold risk of coronary events.
• It is estimated that over 40% of the population is not consuming enough folate to keep homocysteine levels low.
• Elevated homocysteine levels are thought to interfere with collagen cross-linking and may play a role in osteoporosis. Homocysteine interacts with aldose groups found on collagen and leads to structural defects in collagen. In vitro studies have demonstrated that homocysteine increases osteoclastic activity leading to bone resorption.
• Folic acid supplementation reduces homocysteine levels even if the person is not deficient. Simple supplementation can reduce mild homocysteine elevation in virtually all cases. Folic acid supplementation is more effective than dietary folate at lowering homocysteine levels

How can homocysteine levels be reduced?
The enzyme that metabolizes homocysteine into methionine uses folate and B12 as cofactors. Vitamin B6 is also an important cofactor for methylation enzymes. Trimethylglycine is a methyl group donor and can reduce homocysteine plasma levels by as much as 30%. Trimethylglycine is the most effective homocysteine lowering substance known.

Homocysteine + has been formulated to include the cofactors and methyl donors necessary for the methylation of homocysteine into other harmless amino acids. Homocysteine + will help protect your heart by reducing plasma levels of homocysteine. Homocysteine + is AOR’s basic formula for addressing homocysteine issues, for a superior formulation please refer to Ortho-Methyl in our advance series.

Homocysteine+ test results
The value of Homocysteine+ was recently tested in a study from the University of East London. A sample population composed of healthy and active participants between 14 and 68 years old was randomly allocated into test and control groups and given either Homocysteine + or control pills with no supplements to be taken three times daily for six weeks. Blood samples were taken at the beginning and end of the testing period and the levels of homocysteine were measured by lab techs who did not know which samples were from which group.

It was found that changes in homocysteine levels in the control group were not statistically significant, but participants who took Homocysteine+ had a significant decrease in their levels. The baseline levels of homocysteine were higher with age and lower with regular exercise and high folate intake, although discrepancies showed that even young adults who exercise regularly may have high levels of homocysteine. It was also determined that homocysteine levels were lowered through supplementation regardless of the initial levels, so the vitamins can be beneficial to people even if their homocysteine levels are not dangerously high. Those whose initial levels of homocysteine were high enough to put them in the “at risk” category experienced a dramatic homocysteine drop. Since a reduction of as little as 3 umol/L in homocysteine levels can significantly decrease the risk of heart attack, these participants reduced their risk of disease in only 6 weeks of supplementation.

Only three of the participants had any major change in their diet or exercise regime during the study, indicating that the observed drop in homocysteine levels was caused by Homocysteine+ supplementation and not by other factors. Those whose levels changed the least appeared to be the participants who neglected to take the vitamins regularly. The three participants who made a positive change to their lifestyles over the six weeks experienced very great drops in their homocysteine levels. Thus the best way to achieve healthy levels of this amino acid is to combine a good diet and moderate exercise with regular supplementation.

References

• Shils M. E., Olson J.A., Shike M., Ross A. C., Modern Nutrition in Health and Disease, 1998, 9th Edition, Baltimore, Lippincott Williams & Wilkins

• Jellin JM, Gregory P, Batz F, Hitchens K, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 3rd ed. Stockton, CA: Therapeutic Research Faculty; 2000

• Herrmann M, Widmann T, Herrmann W. Homocysteine - a newly recognised risk factor for osteoporosis. Clin Chem Lab Med. 2005;43(10):1111-7.

• Verhoef P, de Groot LC. Dietary determinants of plasma homocysteine concentrations. Semin Vasc Med. 2005 May;5(2):110-23. Review.

• Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Homocysteine as a predictive factor for hip fracture in stroke patients. Bone. 2005 Apr;36(4):721-6.

• Cashman KD. Homocysteine and osteoporotic fracture risk: a potential role for B vitamins. Nutr Rev. 2005 Jan;63(1):29-36.

Copyright © 2005, Advanced Orthomolecular Research