By Richard N. Podell, M.D., MPH
People who have chronic fatigue syndrome (CFS) and Fibromyalgia (FM) often struggle with a kind of mental “fog”. We don’t understand why and there’s been little research on how to think more clearly. Mild Cognitive Impairment or MCI presents with a different kind of cognitive “fog” but it’s form might feel familiar. MCI affects some 15-20% of Americans, aged 65 and older. While anyone can develop MCI, the risk is higher among people who have a high blood level of the amino acid homocysteine. High homocysteine also predicts a higher risk for developing full-fledged Alzheimer’s Disease.
We know how to reduce homocysteine with a relatively simple nutritional formula. To test whether homocysteine-lowering B vitamins would actually improve the cognition of people with MCI, medical researchers in the United Kingdom recruited 266 people aged 70 and over, who had relatively mild problems with basic cognitive skills. This study of vitamins and cognition is called the VITACOG study. Once diagnosed, half the subjects were treated with a daily oral pill containing a moderate oral dose of vitamin B12 (500 micrograms), folic acid (800 micrograms) and vitamin B6 (20 milligrams). The control group took a daily placebo. Several forms of cognitive testing were conducted initially and repeated several times during the two years of study.
For those taking the B vitamins, cognitive test scores improved over the two years of active treatment. Scores for the placebo group did not. The advantage for active treatment was statistically significant. The treated subjects who were most likely to improve were those who started out with high blood levels of homocysteine. Homocysteine levels fell in the treatment group, but did not fall for those who took the placebo. People with MCI also tend to have an increased rate of atrophy or loss of brain tissue over time. For those taking the B vitamins, the rate of brain atrophy was significantly slower than it was for those on placebo.
At the start of the study researchers also measured the level of omega 3 fats in the subjects’ red blood cells. For those on the B vitamins cognitive improvement was much higher among those who began with relatively high levels of omega 3s. (Omega 3 fats are the kind found in fish oil.) Having enough omega 3-s on board seems to help the B vitamins do a better job. For those taking the placebo, the level of omega 3s seemed not to make any difference in their scores.
The graphic shows the results of one of several cognitive tests used in the study. This one is the Hopkins Verbal Learning Test with Delayed Recall (HVLT-DR). Those in the top third for their omega 3 blood levels (third tertile) did best.
Beyond the Study
Is the VITACOG study relevant to the brain fog of CFS and FM? The quick answer is we don’t really know because there’s not been much study of our kind of “brain fog.” However, they are relevant to us at least to this degree: If simple treatments can prevent the MCI associated with aging, there are some grounds for hope that our kind of brain fog might also improve.
The strengths of the VITACOG:
Many studies of potential treatments for cognitive problems last only a few weeks or months. This study ran for two years. Many cognitive studies focus on lab rats. This one was done on people. Many studies lack proper control group. This study was well designed.
Other studies using B vitamins to lower homocysteine and help cognition have had mixed results. Therefore, further controlled studies should be done to confirm the results found with VITACOG. We should also be aware that while high homocysteine also predicts increased risks for heart attacks and strokes, controlled studies using B vitamins did not succeed in improving health outcomes. All the more reason why we need more studies to further confirm VITACOG’s more encouraging results.
Thoughts to consider:
VITACOG suggests that the mild cognitive impairment associated with aging might improve if we treat with a homocysteine lowering strategy, combining B vitamins with omega 3 oils. Whether this strategy might also be useful for people with CFS or FM, we cannot yet say.
What You Might Discuss With Your Physician
If you have MCI, or a family history of MCI or Alzheimer’s:
Consider measuring your fasting level of homocysteine. If homocysteine is high, measure also vitamin B12, folic acid and vitamin B6.
If homocysteine is on the high side, discuss whether or not you should add moderate doses of B12, B6 and folic acid to your supplements.
Plasma or red blood cell levels of omega 3 oils can be measured by specialty laboratories. If on the low side, consider increasing your intake of fatty fish or adding a fish oil supplement.
If your concern is with CFS or FM, understand that the VITACOG findings might or might not be relevant to our type of cognitive “fog”.
Although the B vitamin doses used in this study are only “moderately” high and are typically thought to be safe, there have been reports that high blood levels of folic acid might increase the risk for some cancers. The 800 mcg dose of folic acid used in the VITACOG study is only double that of the current recommended dietary allowance. However, other vitamin formulas used to treat homocysteine often contain considerably higher folate doses. Please read the labels.
Also, most nutritionally oriented physicians prefer that people take the natural methyl folate form of this vitamin, not the synthetic folic acid that most vitamin supplements use.
Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial, 2010 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012244
Preventing Alzheimer’s disease-related gray matter atrophy by B-Vitamin treatment, 2013 http://www.pnas.org/content/110/23/9523.short
Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment, 2016 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927899/
Emails for authors affiliated with the VITACOG study: Celeste de Jager, Ph.D, Division of Geriatric Medicine, University of Capetown South Africa: Celeste.DeJager@uct.ac.za ; David Smith, Department of Pharmacology , University of Oxford, UK email:
Richard Podell, M.D., MPH, is a graduate of Harvard Medical School and the Harvard School of Public Health. He has been treating patients with ME-CFS and Fibromyalgia for more than 20 years.
A clinical professor at New Jersey's Robert Wood Johnson Medical School, Dr. Podell see patients at his Summit, NJ and Somerset, NJ offices. His website is DrPodell.org