Life Extension Magazine

Life Extension Magazine November 2003

As We See It

Startling New Findings About Homocysteine

Original research conducted by Life Extension years ago, however, showed that there is a huge individual variability in the amount of B vitamins needed to keep homocysteine in optimal (safe) ranges. Life Extension found that a substantial percentage of members who were taking the recommended potencies of B vitamins were not achieving adequate homocysteine control. In these members with elevated homocysteine, higher doses of vitamin B6 and/or TMG (trimethylglycine) were needed to bring homocysteine down to the safe range.

Doctors who fail to check their patients’ blood for homocysteine regularly and adjust the B vitamin dose accordingly are not going to reduce homocysteine to safe ranges in most of their patients. It is usually up to the patients themselves to take the initiative to inform their doctors that they intend to maintain their blood homocysteine levels below 7-8 µmol/L of blood.

What Causes Homocysteine Overload
Some people have high blood homocysteine early in life, while others don’t manifest dangerous levels until they grow older. According to every scientific study we could find, most aging people accumulate too much homocysteine in their blood. One reason for this is that the methylation detoxification system that normally disposes of homocysteine becomes defective with aging. Healthy methylation reactions convert homocysteine back into its amino acid precursor, methionine. Supplements that facilitate healthy methylation reactions in the body include folic acid, vitamin B12, and TMG.

Homocysteine Overload Increases Heart Attack Risk by 300%
Data from a study of healthy U.S. physicians with no prior history of heart disease show that highly elevated homocysteine levels were associated with a more than three-fold increase in the risk of heart attack over a five-year period.

This finding was published as part of the Physicians’ Health Study that included 14,916 male physicians.11 The Framingham Heart Study (and other studies) has confirmed that elevated homocysteine is an independent risk factor for heart disease.

Another way the body rids itself of excess homocysteine is through the trans-sulfuration pathway, which is dependent on vitamin B6. As long as adequate levels of vitamin B6 are present, homocysteine is converted into beneficial cysteine in the body via this trans-sulfuration pathway.

Those with moderate homocysteine elevation may respond to the daily intake of 800 mcg of folic acid, 600 mcg of vitamin B12, 100 mg of vitamin B6, and 500 mg of TMG. Life Extension has found that aging members sometimes require vitamin B6 in doses ranging from 250 to 1000 mg a day* and/or 1500 to 3000 mg of TMG a day to reduce homocysteine to a safe range (below 7-8 µmol/L of blood). Reducing consumption of foods that contain lots of methionine (such as red meat and chicken) can lower homocysteine.

Scientific studies point to aging, vitamin deficiency, and chronic disease states (such as kidney failure) as common causes of hyperhomocysteinemia.

Scientific Publications Recognize Homocysteine
When looking back at the scientific literature, we could find only 37 published papers about homocysteine and degenerative disease risk in the 1980s.12 Many of these papers stated that homocysteine was not a heart attack risk factor.

In the 1990s, however, the number of published studies swelled to 648, and most of them pointed to homocysteine as a culprit in the development of coronary artery disease and coronary thrombosis (heart attack).13

The last several years have seen an exponential increase in the number of scientific studies about homocysteine. From 2000 to the present, an astounding 553 papers were published about the significant role of homocysteine in the development of multiple age-related diseases.14 In fact, more studies have been published about homocysteine so far in 2003 than in the entire decade of the 1980s.

An example of the kind of recently published research can be found in the August 22, 2003 issue of the journal Circulation Research. This study revealed how relatively low levels of homocysteine (10 µmol/L) can inflict massive damage to the arterial wall via several destructive molecular mechanisms.15

A Sad Case History
A 48-year-old business associate of Life Extension recently stopped by to see one of our doctors. He was concerned because his recent blood test showed a homocysteine reading of 21.2. The doctor warned him about the heart attack risk he faced and advised him to initiate an aggressive homocysteine-lowering program immediately. This busy executive promised he would do so soon but said he had to run out to make an appointment. Three weeks later, while working out in a gym, this man suffered a massive heart attack and died. His untimely death in August 2003 came as a shock to many who had known him for the past 15 years.

We know that homocysteine not only causes chronic damage to the arterial wall, but also increases the risk of an acute arterial blood clot forming. It is possible that had this 48-year-old man’s homocysteine level been brought under control, he might not have suffered this fatal heart attack.

Folic Acid Is Not the Solution
Supplementation with folic acid reduces homocysteine levels in the blood. Folic acid works by facilitating youthful methylation patterns that enable homocysteine to be transformed (remethylated) into the amino acid methionine. Healthy methylation also requires vitamin B12. Many doctors prescribe only folic acid and neglect to provide their patients with adequate vitamin B12. Without vitamin B12, the remethylation process is severely impaired.

Life Extension discovered many years ago that high doses of folic acid by themselves do not sufficiently lower homocysteine levels. In one case, a member taking 20,000 mcg a day of folic acid saw his homocysteine level remain persistently high.

A new study on kidney failure patients reveals just how critical vitamin B12 is in protecting against homocysteine overload. People suffering from end-stage kidney disease often manifest very high levels of homocysteine. In this study, doctors gave one group of patients oral supplements that contained 5000-6000 mcg of folic acid, 6-10 mcg of vitamin B12, and 5-10 mg of vitamin B6. The other group received a (1-mg) B-12 injection weekly in addition to the daily oral supplements.16

In the group receiving the weekly B-12 shot, homocysteine levels decreased by 32%, while the group receiving the oral folic acid, B12, and B6 did not show a change over the 8-16 week study period. What was so impressive about this study is that the subjects initially had normal blood levels of folic acid and vitamin B12. In response to the vitamin B12 injections, serum B12 levels increased more than 60-fold from 625 to 40,400 pmol/L, which resulted in a reduction of homocysteine by an average of 32%. This study showed a direct linear correlation between increased blood levels of vitamin B12 and decreased levels of homocysteine.

One flaw in this study was that the oral dose of vitamin B12 (6-10 mcg) in the control group was very low. Most Life Extension members obtain over 600 micrograms a day of B12. The oral dose of vitamin B6 (5-10 mg/day) used in this study was also below the higher amounts (100 mg and above) taken by most Life Extension members. It is possible that if higher oral doses of vitamins B12 and B6 had been used in this study that compared B12 injections to folic acid-B12-B6 supplements, a reduction in homocysteine may have occurred.

The value of higher oral doses of vitamins B12 and B6 was shown in another published study17 on end-stage kidney disease patients. Those receiving 100 mg of vitamin B6, 1000 mcg of vitamin B12, and 16,000 mcg of folic acid showed a 30% reduction in homocysteine levels—comparable to the 32% reduction seen in patients receiving weekly B12 shots.

While most people can adequately lower homocysteine levels by increasing their oral intake of TMG and vitamins B12 and B6, elderly people sometimes suffer absorption difficulties and need weekly B12 shots that require a doctor’s prescription. For those whose homocysteine levels remain above 7-8 µmol/L despite taking the recommended oral doses of folic acid, TMG, and vitamins B12 and B6, a weekly 1-mg vitamin B12 shot is strongly recommended.