The hidden Cause


Medical journals along with mainstream media have recently reported that homocysteine may be the primary culprit in heart and vascular disease. Homocysteine is a toxic amino acid that is present in everyone. Research has shown that you can decrease your risk of vascular disease by lowering your homocysteine level. The solution to lowering homocysteine is a process called methylation. This is the process of placing a methyl group on a homocysteine. When this takes place, the homocysteine is converted into an essential amino acid called methionine. By using the proper nutritional supplementation as the methyl group, nearly all cases of elevated homocysteine can be dramatically improved. Methylate™ is a strategically developed nutritional formulation to assist in the battle against homocysteine.

Just as important as heart and vascular disease, methylation has a global effect on our entire body.

As researchers continue to study its positive effect on the aging process and other health challenges, the general public will become the beneficiary of the greatest prevention concept to date.

The purpose of this report is three-fold:

(1)It serves to educate people about the role of proper nutrition and exercise in cardiovascular disease.

(2) It helps identify those at risk for early onset of age-related diseases, including heart disease.

(3) It supplies the majority of relevant references for medical professionals.

A must read is the booklet entitled "Your Life Depends On It: Understanding Homocysteine, Methylation and Your Health," written by Paul Frankel, Ph.D. (founder of The Research Corner), with Fred Madsen, Ph.D., and preface by Craig Cooney, Ph.D.

Are YOU at Risk for disorders related to
homocysteine and poor methylation?

1. Do you excercise less than three times a week?

While excercise has long been known to help prevent many diseases including cardiovascular disease, there was no biological explanation until recently, when it was discovered that the risk factor known as homocysteine is reduced during exercise.

2. Is a significant amount of your diet derived from a box, a can, a bag, a freezer, or fast food?

Processing foods removes vital nutrients required to maintain health. Processed foods contain a fraction of the critical vitamins, B-6, B-12, and folic acid. These nutrients are required to lower homocysteine and prevent cardiovascular disease. In addition, lack of these nutrients is related to carpal tunnel syndrome, anemia, polyp formation, rickets, and a variety of neurological and developmental conditions.

3. Did anyone in your family suffer from vascular disease?

Recently, a genetic weakness in the body's ability to lower homocysteine has been linked to premature vascular disease. If your parents, grandparents, aunts, or uncles suffered from strokes, heart attack, angina, or any vascular disease, you are at an increased risk for vascular disease even if all your standard risk factors are normal. Fortunately, researchers have discovered that betain (TMG), combined with B-6, B12, and folic acid, can prevent much of the damage created by this silent genetic defect.

4. Do you eat less than three courses of vegetables and fruits per day, or consume a typical high carbohydrate diet?

The benefits of balance protein intake and an abundance of fruits and vegetables have long been advocated by health professionals. Recently, the government reduced the recommended daily allowance (RDA) for folic acid simply because so few people were obtaining the required amount for proper health -- not because the body suddenly required less vitamins. Only a diet of fresh vegetables and fruits combined with adequate protein can keep our homocysteine levels low and allow for optimal health and longevity. In response to the reality of the American diet, the government has advocated using supplements in many foods, especially the methyl donor folic acid and B-6.

5. Do you eat commercial non-organic vegetables and fail to eat foods high in minerals?

Foods high in minerals include organic vegetables and sea vegetables. Both are common in Japan where both vascular disease and many of the types of cancer found in the U.S. are significantly less common. Minerals such as Zinc, Copper, and Magnesium are required to allow the enzymes that lower homocysteine to function properly and maintain proper DNA methylation (described later).

6. Is there a history of depression, neurological disease, fatty-liver, or "weak" liver in your family?

Often, depression and neurological disease are related to low S-adenosylmethionine levels (SAM), which are directly related to high homocysteine levels and poor methlation. Research journals have shown that the nutritional supplement betaine and the other methyl donors can significantly elevate the level of SAM. SAM is beneficial not only for depression, but has proven useful for some liver problems as well.

7. Do you smoke, or use birth control pills?

Both smoking and birth controls pills elevate homocysteine levels.

If you answer 'YES" to ANY of the questions above, you are at risk for disorders related to homocysteine and poor methylation. There is something you can do about it!

Homocysteine - Past, Present, and Future

Homocysteine is a toxic amino acid that is present in everyone. As a non-essential amino acid, the research on homocysteine got off to a late start, beginning in earnest in the 1960's. Several cases of children dying of vascular damage usually reserved for older people were noted in the medical literature. In 1968-69, Dr. Kilmer McCully studied the cases and noted that the only known problem was a genetic defect in the children's ability to lower homocysteine. He theorized that homocysteine must be able to cause vascular disease, and given the weakness in the current theories, proposed homocysteine as a cause of vascular disease in the general population. Dr. McCully performed a variety of animal experiments confirming his hypothesis, but it would take a large scale human epidemiological study before his hypthesis would be accepted. That study was finally completed in 1994 and published in the Journal of the American Medical Association, authored by another Harvard researcher. Dr. Meir Stampfer (oddly, Dr. McCully was denied tenure at Harvard decades earlier). Since the 1994 study, many studies have confirmed homocysteine's role in vascular disease, from stroke, to myocardial infarction (heart attack) to carotid artery damage and more! Now homocysteine is the most talked about risk factor for vascular disease.

One of the saddest aspects of this history is that for decades the research not only pointed to homocysteine's damaging effect on the vascular system, but it also clearly demonstrated how to control this risk factor. Proper application of nutrition and nutritional supplementation could have saved thousands, if not millions of lives. Today, homocysteine is starting to get the attention it deserves, but still only a small fraction of the population are aware of its role in vascular disease. This is particularly surprising since a recent report in the medical literature demonstrated a greater than 60% decrease in vascular disease among users of nutritional supplements containing some of the nutrients required to lower homocysteine,

With proper nutritional supplementation nearly all cases of elevated homocysteine can be resolved and dramatically improved. Even people with previously diagnosed vascular disease have survival dependent on their homocysteine levels.

Even though homocysteine's role in heart and vascular disease has now been accepted, the field is still in its infancy. Homocysteine can be found in several forms in the blood. Some forms, like homocysteine thiolactone, are thought to be more damaging than other forms. In addition, homocysteine seems to increase the damaging efffects of fibrinogen and lipoprtoein-a, thereby increasing clotting while decreasing the ability of the blood vessels to contract and expand. These damaging effects appear to be separate from the direct damage to the blood vessels by the irritant, homocysteine.

Methylation and Homocysteine

While there is a considerable amount we do not know about homocysteine (like why exercise reduces it), we do know how to use nutritional supplements to reduce homocysteine levels. This is done through three independent routes: (1) using folic acid with vitamin B-12, (2) using trimethylglycine (TMG), and (3) through B-6. The first two are called methylation, and the last is called transsulfuration.

Methylation is the process of putting a methyl group (one carbon atom and three hydrogen atoms), on proteins, enzymes, chemicals, DNA, or amino acids like homocysteine. When a methyl group is transferred from folic acid to homocysteine, the homocystein is converted to the essential amino acid, methionine. When a methy group is transferred from TMG to homocysteine, the homocysteine is similarly converted to methionine (and TMG is converted to dimethylglycine). This process of methylation results in lower homocysteine and an increase in methionine. In fact, nearly twice the dietary level of methionine is produced during this conversion process. Both folic acid and TMG have been used for nearly two decades to lower homocysteine. These two pathways are independent. Some people are better at using TMG to lower homocysteine and others are better at utilizing folic acid. That is why the literature suggests using both TMG and folic acid to lower homocysteine (folic acid requires B-12 for this activity). Such a combined approch, in conjunction with vitamin B-6, can normalize homocysteine in 95% of the people studied (Choline is also used as a methyl donor, as has been noted in JAMA, although its role is secondary to TMG).

Vitamin B-6 and Transsulfuration

The remaining method of lowering homocysteine is through a process using vitamin B-6. This is a separate process from methylation. Using B-6, the cells convert homocysteine to cystathionine and then to cysteine where it is either further processed and excreatedk or used in protein metabolism. This important method of lowering homocysteine is particularly relevant in the U.S. because B-6 is very unstable, and in today's diet of processed foods B-6 is destroyed and usually needs to be supplemented. In addition, B-6 is destroyed by smoking or birth control pills, which can explain the recent rise in vascular disease in women (remember vascular disease is cumulative, so women who started the pill in the 60's are now showing the results).

Supplemental B-6 is usually supplied in the form of pyridoxine HCL, even though the body uses B-6 in the form of pyridoxal 5' phosphate. Some people are not as efficient in converting pyridoxine HCL to pyridoxal 5' phophate, so a combined formulation is often suggested to insure that the B-6 is utilized.

Methylation beyond its role in Homocysteine

Methylation is a process necessary for many biological functions aside from homocysteine. Methylation is involved in maintaining DNA integrity, processing fats, improving neurological function, detoxifying the liver, and is connected to nearly every biochemical process in the body. Several scientific peer-reviewed articles have demonstrated that this methylation process degrades with age, and is associated with a large variety of age-related diseases. Usually, this methylation process occurs through a chemical called s-adenosylmethionine (SAM).

SAM, increased by the dietary methyl donors mentioned earlier, requires, like most enzymatically controlled reactions, proper mineral balance. As a result, many researchers suggest additional minerals to help the body maintain proper methylation.


Special Formulation to Help Lower Homocysteine

Our special Methylation Formula has been carefully formulated to provide the required amounts (in the most bioavailable forms, as mentioned in Dr. Frankel's booklet "Your Life Depends On It: Understanding Homocysteine, Methylation and Your Health," of the most proven methyl donors available, to aide in reducing homocysteine levels.

and Your Health

by Paul Frankel, Ph.D., with Fred Madsen, Ph.D. and Preface by Craig Cooney, Ph.D: Researcher at NCTR, Division of Nutritional Toxicology.

The book discusses...

    (1) How methylation affects homocysteine levels and the relationship of this process to heart and vascular disease;
    (2) How methylation protects DNA and its effect on cancer and aging;
    (3) How methylation affects levels of SAM, which works to protect the liver and acts as an anti-depressant; and
    (4) How to enhance the methylation process using a combination of lifestyle factors and dietary supplementation in order to live a longer and healthier life.

Dr. Paul Frankel received his Ph.D. in Applied Mathematics from Brown University specializing in mathematical biology. He was a Juvenile Diabetes Fellow and the first predoctoral IRTA Fellow at the National Institutes of Health . After several years as a Professor at the University of Southern California, he founded The Research Corner, a company devoted to medical research, updates and educational services. Dr. Frankel has published articles in peer-reviewed medical journals, research journals, and the popular press. Dr. Frankel's interest in methylation was initially academic, but that changed quickly after a CT scan indicated serious problems with his liver. With an inconclusive biopsy, he decided to take TMG along with Chinese herbs, and the next scan showed improvement. Today, Dr. Frankel continues to provide people with information about methylation and homocysteine, while facilitating research projects related to human health.

Dr. Fred Madsen earned a Ph.D. in Animal Nutrition-Physiology from the University of Tennessee in Knoxville in 1974. He spent two years at the Comparative Animal Research Laboratory in Oak Ridge, Tennessee, before working for the pharmaceutical company, Syntex. In 1979 he returned to Knoxville and worked in the animal feed business. During the following 18 years in the feed industry he learned the art of animal nutrition, and is a leader in the formulation of healthy, high performance diets. He is a member of several scientific organizations, including the American Society for Nutritional Sciences (formally the American Institute of Nutrition), and has lectured worldwide on a variety of topics related to disease and diet. Dr. Madsen has written numerous articles in scientific and popular journals. After losing stomach acidity during a trip to China in 1986, he successfully used betaine-HCL, to regain his health. Dr. Madsen then investigated betaine without the HCL, and gained a new appreciation for methylation, becoming aware of its role in the battle against aging and degenerative diseases.

Methylate™ is a strategically developed nutritional formulation to assist in the battle against homocysteine.

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