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June 2003

A New Era for SAMe

SAMe and liver cirrhosis

The liver is Grand Central Station for molecules that chaperone lipids around the body. It is the site where very low-density lipoproteins (VLDL) and cholesterol are synthesized. Despite the general misconception that cholesterol is inherently bad, it is actually a very important substance that functions as the precursor for important steroid hormones such as estrogen, DHEA, androgens and the glucocorticoids. It also is part of bile, which acts as a natural detergent against dietary fat.24

Cirrhosis of the liver is a chronic, diffuse degenerative disease (most commonly induced by alcohol abuse) in which the lobules are infiltrated with fat and structurally altered, resulting in a localized loss of function and an increased resistance to blood flow through the damaged area. Although about a third of all cases are compensated, meaning that there are no clinical symptoms, severe cases of cirrhosis can lead to ammonia toxicity, hepatic coma, gastrointestinal hemorrhage, kidney failure and eventually death.25

Research has shown that SAMe can prevent and, if discovered early enough, even reverse this condition. In a rodent study published in Toxicology and Applied Pharmacology, SAMe completely prevented fatty liver when given at the same time as alcohol.26 Not only does SAMe prevent fat from accumulating in the liver, it prevents cirrhosis-related lipid elevation outside of the liver. Studies have found that the blood cells in people with cirrhosis have a high cholesterol-to-phospholipid ratio, a factor that causes problems with the way liver cells function.27 A group in England recently showed that SAMe dramatically reduces cholesterol and re-establishes healthy levels. That study found that the cholesterol-to-phospholipid ratio decreased substantially in the erythrocytes of people with liver disease two weeks after they were treated orally with 1,600 mg of SAMe.28

The cancer connection

It has long been thought that alterations in the liver caused by alcohol, toxins and diseases can eventually lead to cancer. The proof behind this theory began to appear in 1988, when a team of Spanish researchers studying cirrhosis discovered that it is directly related to deficiencies of S-adenosylmethionine synthetase and phos­pho­lipid methyltransferase, two important enzymes that convert methionine to SAMe and form phospholipids.29 Later studies by researchers at the University of Southern California further revealed that liver cancer cells are totally lacking in liver-specific SAMe synthetase; the genes for this enzyme are completely turned off in liver cancer patients.30 A group at the Institute of Biomedical Investigation in Spain further elucidated the relationship between SAMe synthetase and cancer. Their study found that the immune substance interleukin-2 (IL-2) turns on the SAMe synthetase gene in T-cells. IL-2 is necessary for the growth of immune cells that fight viruses and cancer.31
Many of the chemicals used to induce cancer in lab animals work by inhibiting SAMe. SAMe's role as a methyl donor (a methyl group is a biochemical entity that catalyzes important biochemical reactions in the body) is critical in preventing cancer. The liver appears to be particularly sensitive to under-methylation.32

It is well established that methyl deficiency produces liver cancer in rodents. Methyl deficiency causes a reduction in SAMe levels and a subsequent elevation in S-adenosylmethionine homocysteine (SAH).33 SAH is what remains after SAMe donates a methyl group for biochemical reactions. An enzyme, SAH hydrolase, turns SAH into homocysteine. Homocysteine can be toxic if it builds up within the body, but is typically converted into cysteine (and eventually glutathione) when enough SAMe is present. If, however, SAMe levels are extremely low, nothing gets converted and SAH and homocysteine levels rise. This is when cancer gets its toehold. A low SAMe-to-SAH ratio is step number one in the development of liver cancer. However, re-establishing adequate SAMe levels can reverse the early changes in the process.34

Finally, cancer suppressor genes also are adversely affected by under-methylation. Researchers at the FDA's National Center for Toxicological Research have conducted research showing how under-methylation affects the p53 tumor suppressor gene. They have found that rats fed a diet deficient in SAMe precursors (methionine, choline and folic acid) accumulate DNA strand breaks in certain areas of the p53 gene within days. DNA strand breaks translate into a defective or non-functioning p53 protein. Without p53 to stop them, some types of cancer cells will run wild.35

Other liver disorders respond to SAMe

It seems that almost any liver disease may be improved with SAMe therapy. Cholestasis, for example, is a common condition of insufficient bile. While this problem may not generate as much awe and public scrutiny as cancer, nonetheless it can be a serious condition resulting in anything from painful gallstones to death.36

Among the usual causes of cholestasis are estrogen-replacement therapy, birth control pills, certain drugs (including antidepressants) and pregnancy. Studies into the effects of SAMe on cholestasis have found that it protects against this disorder at oral doses of between 600 mg and 800 mg per day.1 These findings were further supported by the recent U.S. government study, which concluded that SAMe is an effective treatment of cholestasis during pregnancy.

The prevention of liver disease is just as important as the prevention of heart disease and cancer. Like these two killers, liver diseases can be prevented by simple yet very effective dietary means. No person escapes liver damage. Chemicals in air and water, drugs, radiation, pesticides, hormones and drugs in meat, fungicides on grains, bacteria, parasites and other entities constantly assault us. The liver must deal with all of them on a daily basis. It generates a massive amount of free radicals during detoxification. Helping the liver is one of the simplest and most important steps persons can do for their health. It is very likely that many diseases in other organs begin when the liver can't do its job.

The future of SAMe

Obviously, SAMe's importance to maintaining biological stability cannot be overstated. Clear evidence exists showing that SAMe is an effective treatment for many age-related disorders including depression, arthritis and liver disease. But researchers aren't stopping there. Currently, studies are underway examining the relationship between SAMe deficiency and numerous other diseases associated with advanced age, such as cancer, Parkinson's disease, Alzheimer's disease, heart disease, Addison's disease, senile dementia and sleep disorders. Considering the far-reaching effects already discovered about this extraordinary compound, undoubtedly it will soon become a major focus of supplemental medicine.

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