Homocysteine Reduction

TMG and Zinc: Bringing Homocysteine Under Control

Other nutrients that encourage the remethylation of homocysteine include TMG and zinc, both of which enhance the action of B vitamins.

TMG operates along a different pathway than the B vitamins. In fact, some individuals who have a severely elevated homocysteine level respond only to TMG because its activity is limited to the liver and kidneys. To decrease a severely elevated homocysteine level, repeated high doses of TMG must be taken throughout the day. One small study found that TMG supplementation taken concurrently with vitamin B6 and folic acid significantly reduced homocysteine (Dudman NP et al 1996).

Zinc acts in concert with vitamin B6 to promote remethylation of homocysteine to methionine. Zinc is also needed for the conversion of homocysteine to cysteine and glutathione. (For safety information on zinc, see the Safety Caveats section at the end of this chapter.)

Removing Excess Homocysteine

While the remethylation pathway recycles homocysteine back into methionine, the transsulfuration pathway removes it. In the transsulfuration pathway, homocysteine is condensed with serine to form cystathionine, which is converted into cysteine. In turn, cysteine is converted into glutathione, taurine, and sulfate waste products that are flushed from the body in urine. All of these reactions occur with the help of vitamin B6.

Besides vitamin B6, other nutrients that strengthen the transsulfuration of homocysteine include:

• SAMe—SAMe is derived directly from methionine. Its job is to provide methyl groups for reactions throughout the body, including the methylation of nucleic acids (RNA and DNA), proteins, and structures throughout the brain. SAMe is the precursor to such nutrients as creatine, glutathione, taurine, L-carnitine, and melatonin and can be found in almost every tissue in the body. It has been studied in the treatment of depression, schizophrenia, demyelination diseases, liver disease, dementia, arthritis, and other conditions. It is also necessary for normal circadian rhythms. High doses of SAMe, 1600 milligrams (mg) daily, increased phosphocreatine levels in the human brain (Silveri MM et al 2003), indicating that SAMe is important in forming creatine. Although SAMe is part of the methionine cycle, taking supplemental SAMe does not increase the production of homocysteine (Devlin TM 2001). It does, however, encourage the conversion of homocysteine to cysteine and glutathione (Devlin TM 2001), thus lowering homocysteine levels. (For safety information on SAMe, see the Safety Caveats section at the end of this chapter.)
• Selenium—The trace mineral selenium is necessary for the antioxidant activity of glutathione, which is converted from homocysteine. Selenium deficiency has been shown to increase oxidative damage in animals. By boosting selenium levels, you can raise your level of glutathione and help lower your homocysteine level (Devlin TM 2002).
• N-acetyl-cysteine—Consuming N-acetyl-cysteine may reduce homocysteine levels by encouraging the production of cysteine, which is critical to the conversion of homocysteine to glutathione. By increasing the production of cysteine, it may be possible to boost the amount of homocysteine converted into glutathione.
• Cysteine—Like N-acetyl-cysteine, cysteine supplementation may prevent the release of stored homocysteine into the bloodstream. The Vitamin Depot Online.comFoundation favors maintaining an adequate level of cysteine to maintain normal glutathione levels.

Inhibiting the Formation of Homocysteine

Not all the homocysteine created is released directly into the bloodstream as free homocysteine. In fact, less than 1 percent of the homocysteine in the blood is free. The majority, about 98 to 99 percent, is bound to proteins in the blood and considered stored.

This store of homocysteine may be released in response to decreased methylation or oxidative damage, or in response to other influences. Nutrients that have been shown to inhibit the release of homocysteine include:

• Creatine—Somewhere between 50 and 90 percent of the SAMe required by the body goes into the production of creatine (Devlin TM 2001; Finkelstein JD et al 1984; Lee H et al 1998; Silveri MM et al 2003; Stead LM et al 2001). Supplementation with creatine diminishes the need for SAMe, reduces formation of homocysteine, and the need for homocysteine remethylation. In animal studies, supplementation with creatine for 2 weeks reduced homocysteine levels by 25 percent (Stead LM et al 2001).
• Choline-producing nutrients—SAMe is involved in the production of choline. By taking choline-producing nutrients, your body produces less SAMe, which reduces the amount of homocysteine needed. Choline-producing nutrients include cytidine diphosphate (CDP) choline, lecithin, alpha-glycerylphosphorylcholine, and choline chloride.