When homocysteine is not completely broken down by the body, it becomes a very dangerous substance, causing clotting, oxidization, atherosclerosis and blocked blood flow. Increased blood levels of homocysteine usually indicate faulty methionine metabolism. If this biochemical pathway is defective high homocysteine levels can cause clotting, increased oxidation, and can injure the blood vessel wall, allowing cholesterol and other fats to infiltrate into the wall and create what is called a foam cell; thereby blocking the blood flow and creating blood wall plaque.  

When homocysteine is broken down properly, it can supply the body with many necessary substances that in turn aid other normal chemical reactions. For example, processes such as cartilage rebuilding, bone regeneration, liver detoxification, and adrenal gland support come from substances supplied when the normally functioning body breaks down homocysteine. The supplementation required to correct homocysteine levels in a person's blood are the B vitamins folate, B3, B6, and B12. Other substances involved in this critical problem are an extract of red beets called betaine, and the minerals molybendum and magnesium.

A major study involving 80,000 nurses over 14 years showed that, for example, for every 200 mcg of folate consumed on a daily basis, heart disease fell by 11%. For every 2 mg of B6, heart disease fell by 17%. An increased blood homocysteine level has been implicated in the cause of osteoporosis. It has been suggested by the major medical journal, Metabolism, that folic acid could be a useful supplement to prevent osteoporosis. Perhaps it is the effectiveness of folic acid in helping to deal with elevated homocysteine levels that is the link this journal has observed.

A recent large European research project demonstrated that low B6 consumption increased heart disease and stroke by 200%. Stress, excessive exercise, and overcooked food can decrease B vitamins in your body. Vitamin B12 is especially vulnerable to overcooking even in a microwave oven. I would urge readers to investigate homocysteine further by consulting with a knowledgeable health care professional. Homocysteine metabolism is best dealt with by a well-formulated nutritional supplement designed to combat this problem.

HOMOCYSTEINE

Homocysteine (pronounced homo-SIS-teen) is an amino acid and is found normally in the body.  Its metabolism is linked to that of several vitamins, especially folic acid, B6, and B12.  Deficiencies of those vitamins may cause elevated levels of homocysteine.

In recent years, studies have accumulated suggesting that a high level of homocysteine increases a person's chance of developing heart disease, stroke, and peripheral vascular disease (a reduced blood flow to the hands and feet). In September 1995, the National Heart, Lung, and Blood Institute (NHLBI) convened a special panel to review the scientific evidence about homocysteine's possible link to heart disease.  The information that follows is based on the panel's conclusions.

Briefly, the panel said that an elevated homocysteine level appears to increase the risk of heart disease, stroke, and peripheral vascular disease.  However, no studies have been done to show that lowering the homocysteine level reduces the risk of heart disease.  The panel stressed that more research, especially a clinical trial, must be done to understand the possible association between the level of homocysteine and heart and related diseases.

HOMOCYSTEINE AND HEART DISEASE

Various studies have found that persons with elevated levels of homocysteine in their blood are at an increased risk of heart and vessel disease.  These studies include the Physicians' Health Study, the Tromso Study from Norway, the Framingham Heart Study, and a meta-analysis of nearly 40 studies. Some studies indicate that persons with elevated homocysteine levels tend to also have other risk factors for heart disease: high blood pressure, and high blood cholesterol.

WHY HOMOCYSTEINE?

Much more basic research must be done before scientists understand how an elevated homocysteine level affects the development and progression of heart disease.  However, scientists have several theories:  First, a high level of homocysteine may be involved with the process called atherosclerosis, the gradual buildup of fatty substances in arteries. Homocysteine also may make blood more likely to clot by increasing the stickiness of blood platelets.  Clots can block blood flow, causing a heart attack or stroke.  Increased homocysteine may affect other substances involved in clotting too.  Finally, higher homocysteine levels may make blood vessels less flexible--and so less able to widen to increase blood flow.

WHAT DETERMINES HOMOCYSTEINE LEVELS?

Individuals differ in their levels of homocysteine.  Two key factors affect a person's homocysteine level--genetics and environment.

• Genetics: Genetic factors help regulate the level of homocysteine in the blood. For instance, genetic flaws (mutations) can affect homocysteine's metabolism.  The NHLBI Family Heart Study found families with genetic mutations in the enzymes involved in homocysteine metabolism. The NHLBI Framingham Heart Study and other investigations have found a relationship between elevated homocysteine levels and families with early heart disease.

• Environment: The level of homocysteine in the blood also is affected by the consumption of vitamins, especially folic acid, B6, and B12. Data from the Framingham Heart Study show that only 30-40 percent of the population was getting 200 or more micrograms of folic acid in their diet.  The data indicated that for many persons an intake of at least 400 micrograms was needed to keep homocysteine levels from becoming elevated. Data also indicate that homocysteine levels are higher in older persons than younger ones, and in women after menopause than in those before. But more research is needed to confirm and explain these differences.

WHAT LIES AHEAD?

The September NHLBI panel called for more research to help answer the many questions about homocysteine's possible role in the development and progression of heart disease and stroke.  These questions include:

1. Does homocysteine damage blood vessel walls?

2. What regulates the level of homocysteine in the blood and how?

3. What happens to heart disease when homocysteine levels drop?

4. What are the differences in homocysteine levels among men and pre-and post-menopausal women?  If significant differences exist, why?

5. Can keeping homocysteine levels low prevent heart disease and stroke?

6. Can reducing homocysteine levels prevent repeat heart attacks?

7. What is the best amount and of which vitamins to prevent heart attack and stroke?

8. Does the homocysteine level interact with known modifiable risk factors for heart disease?

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HOMOCYSTEINE AND HEART ATTACKS

Heart disease is the No. 1 killer in the U.S., killing more people than cancer, infectious diseases, and homocides combined. Nearly a third of all victims will not survive their first symptom. Half of all victims won't reach the hospital alive. For the past few decades, cholesterol has been the demon of heart disease. Fat consciousness has become America's favorite dietary preoccupation, with entire industries growing up around the idea of reducing dietary fat and cholesterol. While cholesterol is associated with heart disease in some studies, and Americans do eat too much fat, it appears that cholesterol may have less to do with heart disease than most people think. A much stronger case has emerged for a toxic amino acid called homocysteine. Homocysteine is a naturally synthesized by-product of methionine metabolism. If the right cofactors are present, it will eventually convert to cysteine and other beneficial compounds. If the cofactors are lacking, it will build up to toxic levels.

Data from a study on healthy U.S. physicians with no prior history of heart disease shows that highly elevated homocysteine levels are associated with a more than three-fold increase in the risk of heart attack over a five-year period. This finding was published in 1992 in JAMA as part of the Physicians' Health Study. The study included 14,916 male physicians; it is the same one that showed the benefits of aspirin. The Framingham Heart Study and other studies have confirmed that elevated homocysteine is an independent risk factor for heart disease. It is especially imperative for people with a family history of cardiovascular disease to control their homocysteine levels. In one study, 37 men and women with early familial heart disease had 29% higher levels of homocysteine than controls. Dr. Rene Malinow of the Oregon Health Sciences Center concluded that some cases of elevated homocysteine could be the result of an inherited abnormality. This would be one explanation for premature coronary artery disease that runs in families. Mostly, however, elevated homocysteine levels can be traced to inadequate or improper nutrition.

The Different Forms Of Heart Disease

Cardiovascular disease manifests as peripheral artery disease, coronary artery disease, myocardial infarction (heart attack), stroke, aneurysm, thromboembolism, extracranial carotid artery and stenosis. As an artery (or vein) becomes diseased, the inner arterial wall becomes thick - a condition known as arteriosclerosis. Cells lining the artery proliferate and combine with protein and lipids in a mass called an atherosclerotic plaque. Plaques are commonly the first indication of cardiovascular disease. Plaques change with time, gathering cholesterol and fat, finally becoming atheromas. Atheromas distort the artery wall, allowing calcification. Eventually, the inside of arteries become so rough that if you run your fingers over them, they feel like bits of broken glass. When an atheroma blocks blood to the heart, it is referred to as a heart attack. When it blocks blood to the brain, it is a stroke. If the penile artery is damaged or occluded, impotence results. Partial blockage in the chest (which causes pain) is referred to as angina, and weaknesses or rupturing of the arteries or veins are referred to as aneurysms.

Homocysteine is thought to initiate these events by irritating the inner lining of arteries and veins. In addition, it was recently reported in the journal Circulation that hyper-homocysteinemia (high homocysteine) impairs blood vessels' ability to dilate, or expand. Millions of dollars are spent annually on drugs designed to lower blood pressure by dilating blood vessels. It is likely that in some people, this life-threatening problem could be reversed by the supernutrients that lower homocysteine.

Stroke and Homocysteine

According to a study in the European Journal of Clinical Investigation, 40% of stroke victims have elevated homocysteine compared to only 6% of controls. The study found increased homocysteine in lacunar, hemorrhagic and embolic strokes. A study published in Lancet in 1996 showed that even after adjustment for other risk factors, homocysteine was an independent risk factor for stroke and arterial thrombosis in patients with the autoimmune disease lupus.

Another study published in Lancet came to the same conclusion after studying 107 middle-aged British men who participated in a 2-year investigation. The authors concluded that "these findings suggest that homocysteine is a strong and independent risk factor for stroke." It has even been reported that the level of homocysteine in blood correlates with the thickness of arteries. And it was reported in the Journal of Nutrition that men with levels of homocysteine above 14 mmol/L had a greater than 50% chance of stenosis in an extracranial carotid artery, whereas men with levels below 9.1 mmol/L only had a 27% incidence of stenosis. (The data for women were slightly different. Women with levels of homocysteine greater than 14.3 mmol/L had a 39% chance of having carotid artery stenosis: below 9.1 mmol/L, their chances were about even with men).

Known for Over Two Decades

In 1982, Edward Gruber and Stephen Raymond of MIT wrote in their book, Beyond Cholesterol: B6, Arteriosclerosis and Your Heart: "Homocysteine rapidly induces the initial states of arteriosclerosis and cholesterol's effects are not apparent." A comparison of the data on homocysteine with the data on cholesterol illustrates the strength of the homocysteine theory. There are many problems   with the theory that dietary cholesterol causes heart disease. For one thing, non-oxidized cholesterol is not atherogenic in animals. Further, dietary cholesterol doesn't cause vascular disease in animals except under extreme conditions. Heart and vascular disease can be observed in the complete absence of added dietary cholesterol in animals. The cholesterol hypothesis preaches that a multitude of things increase the risk of heart attack. The list includes triglycerides, lipoprotein(a), fibrinogen, smoking, blood pressure, inactivity and poor genetics. Such a multiple risk factor approach should raise a red flag. Dr. Lewis Thomas (former president of Memorial Sloan-Kettering Cancer Center) has stated that every disease turns out to have one central mechanism of action.

Cholesterol has too many ifs, ands and buts to be the cause of heart disease.

Levels of cholesterol in blood do correlate with heart disease. However, cholesterol is no longer thought to be the cause of heart disease. Also, a recent study by Dr. Franziska Loehrer and co-workers at University Hospital in Switzerland showed that cholesterol and triglycerides failed to demonstrate a statistically significant correlation with coronary artery disease. Elevated homocysteine, low S-adenosylmethionine (SAM), age, and body mass index did. According to Dr. Loehrer: "...high levels of homocysteine occur before the disease. The finding of similar homocysteine values in patients after an interval (of approximately) one year supports the idea that this parameter [homocysteine] plays a role in the disease process and is not just altered by the disease itself. Homocysteine is a clearly-established risk factor for heart disease - a better predictor of heart attacks than cholesterol.

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As We See It: Inflammation and Heart Disease
by William Faloon

A growing consensus amongst scientists is that common disorders such as atherosclerosis, colon cancer and Alzheimer's disease are all caused in part by a chronic inflammatory syndrome. The New England Journal of Medicine recently published three articles showing that the presence of blood indicators of inflammation are strong predictive factors for determining who will develop coronary artery disease and suffer cardiac-related death. The good news is many supplements appear to suppress these dangerous inflammatory components of blood.

One of the inflammatory markers The NEJ of Medicine identified is a protein called fibrinogen. High fibrinogen levels can induce a heart attack via several mechanisms, including increased platelet aggregation, hyper-coagulation and excessive blood thickening. The NEJ of Medicine studies showed that those with high levels of fibrinogen were more than twice as likely to die of a heart attack. Another inflammatory marker reported on was C-reactive protein. This marker indicates an increased risk for destabilized atherosclerotic plaque and abnormal arterial clotting. When arterial plaque becomes destabilized, it can burst open and block the flow of blood through a coronary artery, resulting in an acute heart attack. One of the NEJ of Medicine studies showed that people with high levels of C-reactive protein were almost three times as likely to die from a heart attack.

Why are cardiologists so slow to react? It was back in 1996 that there appeared published article showing that high levels of fibrinogen represented a significant risk factor for heart attack and ischemic stroke, based on studies dating back to the 1980's showing that people with elevated fibrinogen levels were more likely to die from a cardiovascular-related disease. Despite numerous studies linking elevated fibrinogen to increased heart attack risk, few doctors bother to check their patients blood levels of fibrinogen or other correctable risk factors such as homocysteine and C-reactive protein. When physicians are challenged to incorporate these published findings into their clinical practice, a common response from doctors who appreciate the importance of these tests is that managed care (HMOs and PPOs) refuse to pay for them. Other doctors demand a higher standard of proof before they test their patient's blood for what they consider to be "newly identified" cardiac risk factors.

The sad fact is that the majority of practicing physicians are not even aware of these documented methods of measuring cardiovascular risk factors such as C-reactive protein, fibrinogen and homocysteine in the blood. Sad to say, many physicians are educated by their pharmaceutical sales reps who have no interest in alerting physicians to nutritionally-related testing. As a result of physician ignorance combined with pharmaceutical industry influence, many Americans suffer progressive debilitating congestive heart failure or cerebral circulatory impairment when the underlying causes could be corrected if the physician ordered and properly interpreted these blood tests.

Sources of Inflammatory Markers and Cytokines.
New England Journal of Medicine, October 19, 2000.

Correcting inflammatory risk factors
Cardiovascular risk factors such as fibrinogen and C-reactive protein are produced in the liver by pro-inflammatory cytokines called interleukin-1B, interleukin-6 and tumor necrosis factor alpha. Supplements such as DHEA can suppress excess production of some of these dangerous cytokines. One recent study showed that interleukin-6 by itself increased the risk of heart attack, even after adjustment for the elevation in C-reactive protein induced by interleukin-6. Both vitamin K and DHEA suppress interleukin-6, which helps explain why these supplements have been shown to protect against such a wide range of age-related diseases.

As far as suppressing the dangerous tumor necrosis factor alpha and interleukin-1B cytokines, nettle leaf extract appears to be the most effective dietary supplement. Nettle leaf extract is found in many popular formulas. To protect against fibrinogen-induced heart attack, agents that inhibit platelet aggregation reduce the risk that fibrinogen will cause an abnormal arterial blood clot. Popular platelet aggregation inhibitors include aspirin, green tea, ginkgo, garlic and vitamin E.  For optimal protection against the formation of arterial blood clots, it makes sense to utilize therapies that directly lower elevated fibrinogen levels - (read up on Nattokinase).

Diet-wise, high doses of fish or olive oil have been shown to lower fibrinogen in humans with elevated fibrinogen levels.(30-31) Excessive homocysteine blocks the natural breakdown of fibrinogen by inhibiting the production of tissue plasminogen activator (tPA).(32) Folic acid , TMG, vitamin B12 and vitamin B6 reduce elevated homocysteine levels. Vitamin C, in pharmacological doses, has been shown to break down excess fibrinogen. In one study, heart disease patients were given either 1000 mg or 2000 mg a day of vitamin C to measure the fibrinogen breakdown effect. At 1000 mg a day, there was no detectable change in fibrinolytic activity or cholesterol. At 2000 mg a day of vitamin C, there was a 27% decrease in the platelet aggregation index, a 12% reduction in total cholesterol and a 45% increase in fibrinolysis (fibrinogen breakdown) activity.

An additional marker of heart attack risk Troponin T is a blood marker of heart muscle damage. A recent study showed this marker is the most powerful long-term predictor of cardiac death in those suffering from underlying heart disease. Compared to patients with the lowest levels of troponin T, those with the highest troponin T blood levels were almost 13 times more likely to die over a 37-month period. Why is troponin T such a powerful predictor? It turns out that even those with a minor elevation of troponin T have a larger number of tiny coronary artery blood clots, complex atherosclerotic coronary artery lesions and impaired coronary artery blood flow. Those with elevated troponin T levels, therefore, are the heart attack patients most likely to benefit from antiplatelet and antithrombotic therapies. The type of "troponin" blood test preferred by most clinical laboratories is called Troponin I." (Repeat: check out Nattokinase)

Taking charge of your own health
It has become increasingly apparent that people will have to take a more  active role in protecting their health. That means those who are concerned about optimal health are going to have to stand up to their doctors and demand that certain blood and other diagnostic tests be performed, whether their physician agrees with them or not! It is high time that humans stop sacrificing their lives because of the inability of doctors and insurance companies to recognize diagnostic approaches that are substantiated in respected medical journals.

Managed care, physician apathy and FDA over-regulation is a lethal combination that is causing over one million Americans to needlessly die every single year. In the meantime, those with chronic degenerative disease should take a pro-active role in their health care. If your physician does not appear to care about keeping you in an optimal state of health, find another doctor! Don't become a victim of the current broken-down healthcare system that fails to incorporate scientific findings into the clinical practice of medicine.

Don't let complacent doctors put you at risk for heart disease and stroke. The following chart shows the most common blood tests that can help reveal underlying cardiovascular disease risk factors. As can be seen on the chart below, blood test results that conventional doctors accept as being "normal" can be lethal to you. In other words, what the "Standard Reference Range" allows is not always a practical indicator for where your "optimal" level should be.

In many cases, a "Standard Reference Range" reflects what is expected to be seen in the average population. Since cardiovascular disease remains the number one killer of Americans, you don't ever want to be part of the "average" range when it comes to cardiovascular disease risk factors. By keeping your blood levels in the "Optimal Range," rather than the average "Standard Reference Range," you take advantage of the increasing volume of evidence showing that most heart attacks and strokes are preventable.

As you can see, the "Standard Reference Range" often dangerously differs from what the published research indicates is protective against cardiovascular disease.

There are numerous published studies indicating that cholesterol levels should ideally be under 200.  Many researchers believe it is more important to concentrate on suppressing dangerous LDL cholesterol and increasing beneficial HDL levels. If other risk factors such as homocysteine, fibrinogen, C-reactive protein, etc. are individually adjusted to reflect "optimal" ranges, then a slightly higher total cholesterol of up to 220 might be acceptable.

Please note that cholesterol levels below 180 present increased risk of hemorrhagic stroke and other diseases, so it is important that people maintain a minimal amount of cholesterol, i.e. 180 milligrams per deciliter of blood. It is important to note that in the past, cholesterol levels well above 200 were considered within the "normal" reference range.