Homocysteine and Brain Health
David Perlmutter, MD, FACN
Abstract
While the term homocysteine might not be familiar to most people, it should be. That's because homocysteine, an amino acid found in the blood, may represent a more important risk factor for coronary artery disease and stroke than the more familiar cholesterol. Over the past three decades physicians have been vigorously checking their patients' cholesterol levels no doubt spurned on by the development of various pharmaceutical interventions designed to lower cholesterol to levels deemed "safe." It is perhaps because there are no specific drugs for homocysteine that this easily modifiable risk factor has received such little attention - until now.
In a recent editorial in the prestigious New England Journal of Medicine ( February 14, 2002), Joseph Loscalzo, MD of the Boston University Medical Center provides a compelling overview of the mechanisms relating elevated levels of homocysteine to various forms of vascular disease. Not only is homocysteine directly toxic to the cells lining arteries, but in addition, homocysteine has now been shown to initiate various biochemical processes directly linked to cell death. Of the various cell types that suffer most when homocysteine is elevated, brain neurons are perhaps the most sensitive.
In the same issue of the New England Journal of Medicine, researchers from Boston University School of Medicine describe a direct relationship between elevated homocysteine and risk for Alzheimer's disease. The researchers measured baseline homocysteine levels in 1092 subjects and followed them for 8 years. There was a dramatic increased risk for Alzheimer's disease after the 8 year period in the group of individuals with the highest homocysteine levels. As the authors stated, "The results of our prospective, observational study indicate that there is a strong, graded association between total plasma homocysteine levels and the risk of dementia and Alzheimer's disease. An increment in the plasma homocysteine level of 5 _mol per liter increased the risk of Alzheimer's disease by 40 %. A plasma homocysteine level in the highest age-specific quartile doubled the risk of dementia or Alzheimer's disease."
Aside from dramatically increasing the risk for Alzheimer's disease and dementia, homocysteine has now been directly linked to dramatically increased risk of so-called "silent strokes" now so commonly seen on brain MRI scans. In an article entitled Homocysteine, Silent Brain Infarcts and White Matter Lesions: The Rotterdam Scan Study, researchers publishing their results in the March 2002 issue of the journal Archives of Neurology evaluated brain MRI scans and homocysteine levels in 1,077 people aged 60-90 years. Their results once again revealed a profound relationship between elevation of homocysteine and risk for a brain damaging disease. The risk of a silent stroke was increased and incredible 250% in those participants with the highest homocysteine levels.
In BrainRecovery.com we described how certain drugs used to treat Parkinson's disease may elevate homocysteine. Actually, any drug that lowers vitamin B6, folic acid or vitamin B12 may raise homocysteine.
Now the good news. Unlike elevated cholesterol which is typically treated using potentially dangerous and expensive medications, elevated homocysteine can almost always be normalized using simple, over-the-counter, inexpensive nutritional supplements. We generally strive to reach a level of 8 or less as a goal for homocysteine control. Any doctor can order a homocysteine level. It's a simple and inexpensive blood test and results are usually available in just a day or two. If elevated, simply adding vitamin B6 100 mg, folic acid 800 mcg, and vitamin B12 1000 mcg each day will normalize homocysteine within 2 months. If on this regimen the homocysteine doesn't quite normalize, try adding trimethylglycine (TMG) 500 mg twice a day. Like the B vitamins, TMG is an inexpensive, non-prescription nutritional supplement available at most vitamin shops.