Cardiovascular Health & You

The Truth about Homocysteine

Homocysteine is one of the most destructive compounds found in the human body. Although oxidized LDL cholesterol (the “bad” cholesterol) is commonly considered the arteries’ worst enemy, homocysteine has emerged as an equally powerful threat to heart health. In fact, research now shows that damage from homocysteine paves the way for LDL to have an even more destructive effect on the vascular system, indicating these two agents can work together to cause heart disease.

Homocysteine is considered a primary risk factor for cardiovascular disease including stroke and deep vein thrombosis. Elevated blood levels of homocysteine also are considered an independent risk factor for atherosclerosis and thromboembolism (the obstruction of a blood vessel by a clot), and are correlated with a significant risk for coronary, cerebral and peripheral vascular disease, myocardial infarction (heart attacks), peripheral vascular occlusive disease, cerebral vascular occlusive disease, and retinal vascular disease. In fact, high homocysteine, even in the absence of other risks, such as smoking and obesity, is a serious but controllable risk factor for heart disease.

Homocysteine is an amino acid commonly found in the blood as a result of protein metabolism. It is mainly derived from another amino acid known as methionine, which is found in a number of food sources primary among them being meat. Blood levels of homocysteine can also be affected by genetic and physiologic factors.

Homocysteine is thought to cause vascular disease because of its effect on blood vessel walls. Homocysteine binds to certain proteins in the body affecting their structure and function. The binding of homocysteine to proteins will degrade and inhibit repair and maintenance of three main vascular connective tissue structures—cartilage, elastin and proteolgycans—making them more susceptible to disease processes, including vascular disease. Homocysteine can damage the cells lining the artery walls (known as the endothelium) in the vascular system. Homocysteine causes a reduction in nitric oxide activity, impairing blood vessels’ ability to dilate and leaving the endothelium more susceptible to oxidative damage. Damaged vascular walls will then allow more low density lipoprotein (LDL) to be absorbed, further harming the vessel. This damage then promotes the growth of new smooth muscle cells within the vessel, which then narrows it. Endothelial damage also allows for increased platelet adhesiveness and activation of the clotting cascade, increasing the risk of cardiac arrest (heart attack) or cerebrovascular accident (stroke).

Genetic Causes of High Homocysteine

Dietary factors, while often cited as the chief cause for elevated homocysteine, are not the only factor. A rare hereditary disease known as homocystinuria results in several systemic disorders and is characterized by the accumulation of homocysteine in the blood and an increased rate of excretion in the urine. Nearly 25% of people with this disorder die from cardiovascular complications before the age of thirty.

10% of the population in general have another more common yet related condition where they are unable to effectively metabolize homocysteine and will be predisposed to the negative effects of elevated homocysteine levels, including blood clots and cardiovascular disease. This disorder is known as a methylenetetrahydrofolate-reductase (MTHFR) polymorphism genetic trait. People that have this condition are unable to effectively metabolize homocysteine and will be predisposed to the negative effects of elevated homocysteine levels, including blood clots and cardiovascular disease.

Other Causes of Elevated Homocysteine

Inadequate B6, B12, Folate: In adults elevated homocysteine levels are usually related to the inadequate intake of B vitamins, particularly folic acid, B6, B12, and betaine (trimethylglycine). The reason these nutrients are so important is that they all act as cofactors in the metabolism of homocysteine. The conversion of homocysteine to cysteine—known as transsulfuration—requires an enzyme called cystathionine b-synthase (CBS) along with vitamin B6 as a cofactor. In the absence of vitamin B6, transsulfuration cannot proceed, and homocysteine begins to build up and damage blood vessels. The conversion of homocysteine back to methionine is called remethylation. Folic acid and vitamins B6 and B12 are required for this reaction. Betaine can also facilitate remethylation. When levels of these nutrients are low, remethylation cannot proceed efficiently, allowing homocysteine to accumulate.

Keeping Homocysteine Levels Low

Lifestyle Modification: Relatively straight-forward lifestyle changes can help to maintain favourable homocysteine levels, including exercise, avoiding alcohol, and eating a diet high in protein. Although a high protein diet might seem contradictory, since homocysteine is produced from an amino acid found in meat, data from a large study demonstrates that the more meat one consume, the lower one’s blood homocysteine level. Since hyperinsulinemia (elevated insulin) is also associated with higher levels of homocysteine, higher meat consumption probably results in a reduction in carbohydrate consumption, and a consequent reduction in insulin levels.

Folic Acid: Folic acid enhances the remethylation process that converts homocysteine into methionine, and thereby further reduces homocysteine levels. Doses of folic acid ranging from 800 mcg up to 5 mg/day have been recommended.

Vitamin B6: Vitamin B6 (pyridoxine) has been safely used in doses ranging as high as 750 mg per day for up to 24 years by patients with elevated levels of homocysteine. This is a remarkable record of safety, considering reports of peripheral neuropathy at doses as low as 500 mg per day of B6. One possible explanation is that since the metabolism of some people diagnosed with hyperhomocysteinemia is so severely altered that, not only can they tolerate such high doses of B6, they may actually require them. More common recommendations for B6 range from 100-300 mg per day.

Vitamin B12 (cobalamin): Vitamin B12 is also a cofactor in the remethylation of homocysteine to methionine. Vitamin B12 is effective in doses up to 1 mg per day. In a small study from the Denver VA Medical Center, physicians treated ten patients with high homocysteine levels with weekly injections of 1 mg of vitamin B12 per week for 8 weeks, followed by monthly injections for the next four months. This single therapy led to dramatic drops in the homocysteine levels of all patients.

Betaine (TMG): Some people are deficient in enzymes required to facilitate transsulfuration or folate-based methylation. Such a deficiency can result in elevated homocysteine levels regardless of the presence of adequate levels of folate and/or vitamin B6. In such cases betaine (tri-methylglycine, or TMG) has been shown to be quite effective in reducing high homocysteine levels by enhancing the remethylation of homocysteine by a different pathway than vitamin B6. Betaine has been shown to be effective in doses of 6 to 9 grams daily.
Conclusion

Homocysteine is considered a primary, independent risk factor for cardiovascular disease and is thought to contribute to a host of other conditions such as miscarriages and difficult pregnancy, bone fractures, strokes, blood clots, depression, dementia, Alzheimer’s and Parkinson’s diseases. Due to this amino acid’s role in a host of diseases, individuals at risk for high homocysteine levels should consider a supplement regimen that includes vitamins B12 and B6, folic acid, and betaine.

Given the deadly consequences of elevated homocysteine levels it is truly remarkable when one considers the ease with which these levels can be reduced and maintained within a safe range by simply taking folic acid (folate), vitamins B6 (pyridoxine) and B12, betaine (TMG), and antioxidants.

References
1. Blum A, Hijazi I, Eizenberg MM, Blum N. Homocysteine (Hcy) follow-up study. Clin Invest Med. 2007;30(1):21-5.
2. Lentz SR. Mechanisms of homocysteine-induced atherothrombosis. J Thromb Haemost. 2005 Aug;3(8):1646-54.
3. Keebler ME, De Souza C, Fonesca V. Diagnosis and treatment of  hyperhomocysteinemia. Curr Atheroscler Rep. 2001;3:54-63.
4. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 1995;274:1049-57.
5. Welch, G.N., Loscalzo, J. Homocysteine and atherothrombosis, New Engl J Med, 1998, 338: 1042-1050.
6. Ray, J.G. Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease, Arch Intern Med, 1998: 158: 2101-2106.
7.  Selhub J, D’Angelo A. Relationship between homocysteine and thrombotic disease [In Process Citation]. Am J Med Sci. 1998; 316:129-41.
8. Moghadasian M, McManus B, Frolich J. Homocyst(e)ine and coronary artery disease. Clinical evidence and genetic and metabolic background. Arch Intern Med. 1997; 157:2299-2308.

Other beneficial nutrients for Cardiovascular Health:

Coenzyme Q10: one of CoQ10’s best-known actions is its ability to protect the health of the heart. Another beneficial application of CoQ10 is for athletes, body builders and performers who want to have both greater endurance and muscle power coupled with reduced recover times after heavy workouts or peak performances. Since cholesterol-lowering statin drugs are known to deplete CoQ10 levels, CoQ10 supplementation is also recommended for anyone consuming these drugs to counteract their toxic effects.

Magnesium: the second-most abundant element within the human cell. Over 300 magnesium-dependent enzymes have been identified to date, underscoring magnesium’s vital role in metabolism. ATP (energy) production, protein synthesis, nerve function and DNA replication are all driven by magnesium-dependent enzymes. As nature’s “calcium channel blocker,” magnesium helps control the excitability of nerves and is essential for relaxation of the heart muscle between beats.

Dietary magnesium deficiency results in altered heart rhythm, and several studies support the value of intravenous magnesium in preventing post-surgical atrial fibrillation. Magnesium is used in the conventional medical model intravenously to treat various types of arrhythmia including atrial tachycardia, atrial fibrillation, ventricular fibrillation and supraventricular tachycardia. Clinically preventing a low magnesium status within the body is an important cardiac protective strategy.

Nattokinase: natto, a fermented soy cheese, contains an enzyme called nattokinase, which has been studied for its clot-dissolving abilities. In one study, 12 volunteers (six men and six women) were fed 200 grams (seven ounces) of natto. A blood sample was taken and the formation of a thrombus (clot) was then artificially stimulated. In those subjects fed natto, the time needed to completely dissolve the clot was cut in half compared to those in the control group. Clinicians have found that nattokinase affects the entire systemic circulation and will help clear blockages from tiny blood vessels as well as the larger vessels

Tocotrienols: important regulators of blood lipids within normal levels, including total cholesterol and LDL cholesterol. Tocotrienols have an inhibitory effect on HMG-CoA reductase, the liver enzyme that is critical to the rate at which cholesterol is synthesized. Tocotrienols also show potential to protect blood vessels by preventing the oxidation of LDL cholesterol, and some studies suggest that tocotrienols may be more effective than vitamin E in guarding against the oxidation of cholesterol. Tocotrienols have been shown to strengthen arterial walls, and to support blood flow through arteries.

Essential Phospholipids(EPL): clinical studies of EPL conducted in Europe show that EPL may play an important role in supporting LDL cholesterol, total cholesterol and serum triglycerides within normal levels, and in supporting healthy HDL cholesterol within normal levels. Studies of EPL suggest it has potential to support the cardiovascular function, increase peripheral brain circulation, and in some cases increase exercise tolerance.

Measures to Protect Your Heart

• Stop Smoking! Reduces the chance of heart attack or stroke from the moment you stop puffing.

• Engage in physical activity or exercise for at least 30 minutes on most days of the week.

• Eating at least 5 servings of fruits and vegetables a day.

• Limit your salt intake to less than 1 teaspoon a day.

• High blood pressure has no symptoms, but can cause a sudden stroke or heart attack. Have your blood pressure checked regularly.

• Diabetes increases the risk of heart attacks and stroke. Control your blood pressure and blood sugar to minimize your risk.

• Being overweight increases the risk of heart attacks and strokes. To maintain an ideal body weight, engage in regular physical activity and adopt a healthy eating diet.

• Manage your stress! Studies have indicated that high stress levels may contribute to heart disease. Take time off to relax and learn how to manage your stress.