Antioxidants Appear No Help for Alzheimer's
The combination of vitamin E, vitamin C, and alpha-lipoic acid did not lower levels of the amyloid and tau proteins that make up the plaques and tangles seen in the brain with Alzheimer's disease, Douglas R. Galasko, MD, of the University of California San Diego, and colleagues found.
The combination did reduce CSF levels of the oxidative stress biomarker F2-isoprostane by 19% but raised a safety concern with faster decline in cognitive scores, they reported online in the Archives of Neurology.
The popular antioxidant coenzyme Q (CoQ) had no significant impact on any CSF measures in the Alzheimer's Disease Cooperative Study antioxidant biomarker trial.
Oxidative damage is widespread in the brain in Alzheimer's disease and contributes to neuronal damage, Galasko's group explained.
Some prior observational evidence has pointed to lower Alzheimer's risk with an antioxidant-rich diet, although prevention trials with supplements have had mixed results, they noted.
Their study included 78 adults with mild to moderate Alzheimer's randomly assigned to double-blind treatment over 16 weeks with the combination of 800 IU vitamin E, 500 mg vitamin C, and 900 mg of alpha-lipoic acid once a day; CoQ alone at a dose of 400 mg three times a day; or placebo.
Vitamins C and E act as antioxidants by controlling dangerous free radicals produced when oxygen reacts with certain molecules, while alpha-lipoic acid spurs production of many antioxidant enzymes in the body. CoQ is an antioxidant that helps protect mitochondria from oxidation.
Serial CSF specimens collected from 66 of the participants showed only small changes from baseline.
Beta-amyloid 42, which accumulates to forms plaques in the Alzheimer's brain, declined by 8 pg/mL from a baseline of 190 pg/mL with the antioxidant combination and by 15 pg/mL from a baseline of 185 in the CoQ group, but neither was a significant difference from placebo.
Tau protein, which forms neurofibrillary tangles in the brain with Alzheimer's, fell by 23 pg/mL with the antioxidant combination from a baseline of 123 and by 9 pg/mL from a baseline of 109 in the CoQ group, but again neither differed from changes with placebo.
Levels of tau phosphorylated at a specific site (P-tau181) likewise declined slightly over the study period for the two antioxidant groups but without a significant difference from placebo.
The one significant change was in CSF levels of the oxidative marker F2-isoprostane, which is stable oxidized arachidonic acid.
The vitamin C and E plus alpha-lipoic acid group saw a 7 pg/mL reduction in F2-isoprostane from a baseline of 38 over the 16 weeks of treatment (P=0.04). The other groups showed no change.
"It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in Alzheimer disease," the group cautioned.
Cognition, measured with the Mini-Mental State Examination, didn't improve in any of the groups. In fact, the decline in scores appeared accelerated in the antioxidant combination group, with a change of -4.6 points over the 16 weeks compared with -2.3 to -2.4 in the other two groups.
The researchers highlighted that as a potential safety concern that needs further careful assessment if longer-term trials are considered. The antioxidants were otherwise well tolerated.
Function, as measured on the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale, didn't change in any group.
The study was supported by a National Institute on Aging grant.
The researchers reported having no conflicts of interest regarding the study; the specific antioxidants studied or the company that makes them, Vitaline, which supplied both study drugs and placebo; or the CSF assays that were measured.
Galasko reported serving as editor of Alzheimer's Disease Research and Treatment, serving on data safety monitoring boards for Elan and Janssen, being an investigator in clinical trials sponsored by Eli Lilly and Avid, and receiving research support from National Institutes of Health grants.
The researchers reported having no conflicts of interest regarding the study; the specific antioxidants studied or the company that makes them, Vitaline, which supplied both study drugs and placebo; or the CSF assays that were measured.
Galasko reported serving as editor of Alzheimer's Disease Research and Treatment, serving on data safety monitoring boards for Elan and Janssen, being an investigator in clinical trials sponsored by Eli Lilly and Avid, and receiving research support from National Institutes of Health grants.
Primary source: Archives of Neurology
Source reference:
Galasko D, et al "Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures" Arch Neurol 2012; DOI:10.1001/archneurol.2012.85.
Comments:
Colenso
03/20/12
Big pharma, little pharma - it makes no difference. Wellness is not to be found in a bottle..
Robert Haile MD
03/20/12
During an acute MI a statin would be of little benefit at all although statins have shown clear primary prevention benefit. Only long term preventative research on antioxidants would be useful to predict if antioxidants would be of benefit in preventing Alzheimer's disease. At this time no prevention use of antioxidants can be made..
Nicholas Pokoluk
03/20/12
The choice of supplement is important to this discussion. To say "antioxidants" is unfair as these antioxidants do not encompass the totality of antioxidants. All antioxidants are not created equal and have different mechanisms of action. Plus antioxidants that also have anti-inflammatory action such as those of curcumin, grape seed extract and EGCG work in totally different ways and have shown to be good candidates for affecting Alzheimer's. This is a dangerous article and can have a very deleterious affect on the public perspective on antioxidants be they in the form of supplements or from natural sources such as vegetables, berries and other botanical sources. This is what is wrong with the reporting of scientific with such bold and disingenuous headlines!.
Ian Biner
03/20/12
What forms of the anti-oxidants were used? This is especially important in the case of alpha lipoic acid and coq10. If the trial was conducted with synthetic ALA, then then entire study is worthless. Similarly, if the study was conducted with ubiquinone, then the 25% of the population who lack the gene SNP to convert it to ubiquinol would have skewed the test results. Given the relative costs of synthetic v natural and ubiquinone v ubiquinol, I would put money on the cheaper supplements being used. I also agree with Jim Brockman's comments re Vitamins E and C. The dose was too low, and if the form of the E was the synthetic, or if the form was the common alpha tocopherol, then once again, the study is worthless..
Jim Brockman
03/20/12
The doses of Vitamin C and Vitamin E used in the study are far too low to give us useful data in regards to their efficacy here especially when compared to the doses of alpha-lipoic acid and Coenzyme Q10. Score another one for the propaganda machine of big pharma I guess. The form of Vitamin E also makes a difference in regards to it's effectiveness as well. Was the typical synthetic alpha-tocopherol version used in this study?.
