by Dr. Leo Galland
With findings that surprised even its chief investigator, a study published in September of this year from Oxford University is receiving tremendous attention.
The researchers found that giving a combination of B vitamins to elderly men and women at high risk of Alzheimer’s disease reduced the amount of brain shrinkage occurring over 2 years by about 50%. Decreased brain shrinkage was accompanied by preservation of brain function. (1)
This is a remarkable finding and an important study for several reasons:
It was a placebo-controlled 2-year experiment, not an observational study.
It used an objective measurement (brain volume loss) that correlates strongly with risk of Alzheimer’s disease and other forms of dementia.
The treatment used was a combination of three B vitamins at the following doses: folic acid 800 micrograms, vitamin B12 500 micrograms, and vitamin B6 20 milligrams. I’ll call this mixture Triple-B therapy; many studies have been done with it, using varied doses of the three B vitamins.
Based on this research, you may think that everyone should take B Vitamins for Alzheimer’s prevention.
But it’s not that simple.
When it comes to B Vitamins, one size clearly does not fit all.
In contrast to popular news coverage of this research, the Oxford study does not indicate that everyone would benefit from taking Triple-B therapy.
In fact, previous research from the Alzheimer Disease Cooperative Study (ADCS) done in the United States, found no beneficial effect of a higher dose Triple-B combination in patients with mild to moderate Alzheimer’s disease. This study, published in the Journal of the American Medical Association (JAMA), actually found an increase in depression among people taking the B vitamins (2).
Together with some recent reports that folic acid supplementation increased cancer risk of certain groups (3-6), the Oxford study emphasizes the need for individualizing risks and benefits when taking any type of dietary supplement.
I have long championed an individualized approach to the use of dietary supplements. That’s the reason I created pilladvised.com, a free online database for learning about how dietary supplements and medications interact.
Given the potential benefits, side effects and interactions, supplements should be used with the same kind of precision usually reserved for drugs.
Wherever the data exists, doctors and their patients should have knowledge of it.
So here’s a look at some of the research on the benefits and risks of taking folic acid, vitamin B12 and vitamin B6.
Important Note: these observations do NOT apply to people who are deficient in these vitamins. They are based on studies of people without deficiency who were given the vitamins as supplements, in placebo-controlled clinical trials.
The Oxford research found that the degree of benefit from taking B Vitamins was directly related to the blood level of a naturally occurring chemical called homocysteine.
Homocysteine is an amino acid normally produced in the body. Measurement of homocysteine is performed by laboratories and hospitals in the United States.
Why is homocysteine important?
High levels of homocysteine may damage blood vessels and are associated with an increased risk of Alzheimer’s disease, stroke and heart attack. Blood levels of homocysteine vary widely and are influenced by diet, the body’s stores of the three B-vitamins (folate, B12 and B6) and a number of genetic factors.
In the Oxford study, people with blood levels of homocysteine less than 9.5 micromoles per liter showed no benefit from B-vitamin supplementation. A similar result was found in another study published in the journal Stroke (7). In both studies, as the homocysteine level went up, the degree of benefit steadily improved.
In the ADCS report mentioned above, most people had homocysteine levels under 9.5, so one would not expect much of a response in that population and the ADCS does not really contradict the Oxford study.
Adverse Effects of Vitamin B
But knowing your homocysteine level is only one step in deciding if B Vitamins might be good for your health. Some studies have shown adverse effects of homocysteine lowering with Triple B therapy even when the homocysteine level was elevated.
Writing in JAMA, Canadian researchers found that giving folic acid (2.5 milligrams per day), B12 (1 milligram per day) and B6 (25 milligrams per day) to diabetics actually increased the rate at which diabetes damaged their kidneys. (8)
Researchers in Norway, publishing their findings in the American Journal of Cardiology, reported that Triple B therapy paradoxically increased cardiac circulatory damage in people who had lots of arterial plaque in their hearts. (9) Their explanation: the damage that homocysteine does to arteries may cause arterial plaque to form, but after there’s a lot of plaque, homocysteine works to stabilize that plaque and bury it in the arterial wall, so reducing homocysteine levels for those people may be harmful rather than helpful. This would explain the disturbing results of another Norwegian study of Triple B therapy, published in The Archives of Internal Medicine: people who had just suffered a heart attack and were given B vitamins for four years had an increased rate of repeat heart attacks, stroke or sudden death (10).
B Vitamins are being intensely studied for their benefits and pitfalls and what emerges is a complex picture.
Depending on who you are, what your condition is, and type of B Vitamins you are taking, to name just three of the many variables, taking them could be beneficial or harmful.
According to the research, some people at high risk of stroke or dementia may benefit from Triple B Therapy, with preservation of brain size, circulation and vision (11). Benefits are likely to be limited to people with homocysteine levels above 9.5 micromoles per liter who do not have advanced arterial disease.
In diabetics, people who have suffered a heart attack and those with severe hardening of the arteries, homocysteine-lowering with B vitamins may actually do more harm than good.
1) PLoS ONE, September 2010 | Volume 5 | Issue 9 | e12244 (pp 1-10). “Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial.” A. David Smith, Stephen M. Smith, Celeste A. de Jager, Philippa Whitbread, Carole Johnston, Grzegorz Agacinski, Abderrahim Oulhaj, Kevin M. Bradley, Robin Jacoby, Helga Refsum.
2) JAMA 2008 300: 1774–1783 “High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial.” Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, et al.
3) J Nutr. 2010 Sep; 140(9): 1661-8. “Plasma folate concentrations are positively associated with risk of estrogen receptor beta negative breast cancer in a Swedish nested case control study.” Ericson U, Borgquist S, Ivarsson MI, Sonestedt E, Gullberg B, Carlson J, Olsson H, Jirström K, Wirfält E.
4) JAMA. 2009 Nov 18; 302(19): 2119-26.”Cancer incidence and mortality after treatment with folic acid and vitamin B12.” Ebbing M, Bønaa KH, Nygård O, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njølstad I, Refsum H, Nilsen DW, Tverdal A, Meyer K, Vollset SE.
5) American Journal of Clinical Nutrition, Vol. 83, No. 4, 895-904 2006.
“Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.” Rachael Z Stolzenberg-Solomon, Shih-Chen Chang, Michael F Leitzmann, Karen A Johnson, Christine Johnson, Saundra S Buys, Robert N Hoover and Regina G Ziegler
6) J Natl Cancer Inst. 2009 March 18; 101(6): 432–435.
“Folic Acid and Risk of Prostate Cancer: Results From a Randomized Clinical Trial
Jane C. Figueiredo,” Maria V. Grau, Robert W. Haile, Robert S. Sandler, Robert W. Summers, Robert S. Bresalier, Carol A. Burke, Gail E. McKeown-Eyssen, and John A. Baron
7) Stroke. 2009 Mar; 40(3): 730-6. Epub 2008 Dec 31. “High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial.” Hodis HN, Mack WJ, Dustin L, Mahrer PR, Azen SP, Detrano R, Selhub J, Alaupovic P, Liu CR, Liu CH, Hwang J, Wilcox AG, Selzer RH; BVAIT Research Group.
8.) JAMA. 2010 Apr 28;303(16):1603-9. “Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial.” House AA, Eliasziw M, Cattran DC, Churchill DN, Oliver MJ, Fine A, Dresser GK, Spence JD.
9) Am J Cardiol 2010; 105:1577–1584. Effect of Homocysteine-Lowering B Vitamin Treatment on Angiographic Progression of Coronary Artery Disease: A Western Norway B Vitamin Intervention Trial (WENBIT) Substudy. Kjetil H. Lølanda, Øyvind Bleie, Are J. Blixa, Elin Strand, Per M. Ueland, Helga Refsum, Marta Ebbing, Jan E. Nordrehaug, and Ottar Nygård.
10) N Engl J Med. 2006 Apr 13; 354(15): 1578-88. Epub 2006 Mar 12 “Homocysteine lowering and cardiovascular events after acute myocardial infarction.” Bønaa KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K; NORVIT Trial Investigators.
11) Arch Intern Med. 2009 Feb 23; 169(4): 335-41. “Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women’s Antioxidant and Folic Acid Cardiovascular Study.” Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE.