Alzheimer's Biomarkers Unaffected By Antioxidants 2012
Adding antioxidant supplements such as vitamin E and vitamin C to the diet does not appear to affect some cerebrospinal fluid (CSF) biomarkers linked to Alzheimer's disease, according to the results of a randomized controlled trial that were published online in Archives of Neurology on Monday.
Antioxidant supplements don't appear to have an impact on cerebrospinal fluid (CSF) biomarkers related to Alzheimer's disease, a clinical trial determined.
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.
First author Dr Douglas R. Galasko, from the Department of Neuroscience at the University of California San Diego, and colleagues describe how they tested for the effects of a combination of vitamin E, vitamin C and alpha-lipoic acid (E/C/ALA) on levels of CSF biomarkers.
Alzheimer's disease is characterized by an abundance of beta-amyloid protein plaques that clog up the spaces between brain cells and tau-based neurofibrillary tangles that clog up the insides of brain cells. Certain proteins in spinal fluid relate to this amyloid and tau pathology and serve as reliable biomarkers for the disease.
Metabolic reactions in the body produce free radicals that interact with other molecules to cause oxidative damage to proteins, membranes and genes. This influences the aging process and is also linked to disease, including cancer and Alzheimer's. In fact, oxidative damage in the brain is widespread among people with Alzheimer's disease.
The body defends against oxidative damage by producing antioxidants to mop up free radicals. Genes, environment and lifestyle (eg diet, smoking, exercise) determine how well it does this.
Increasing intake of antioxidants can boost the body's ability to defend itself against oxidative damage, and Galasko and colleagues write that some observational studies have suggested that a diet rich in antioxidants can reduce the risk of Alzheimer's disease, but randomized clinical trials have shown mixed results.
For their study, Galasko and colleagues looked at changes in CSF biomarkers related to Alzheimer's disease and oxidative stress, cognition and function in 78 patients from the Alzheimer's Disease Cooperative Study (ADCS) Antioxidant Biomarker study.
The patients were placed in three groups.
One group took 800 IU per day of vitamin E (alpha-tocopherol), plus 500 mg per day of vitamin C, plus 900 mg per day of alpha -lipoic acid (E/C/ALA). Another group took 400 mg of the popular antioxidant coenzyme Q (CoQ) three times a day, while the third group was given a placebo.
66 of the patients provided serial CSF samples that were adequate for analysis during the trial, which lasted for 16 weeks.
The results showed that changes in the CSF biomarkers for the amyloid and tau proteins that are related to Alzheimer's disease (alpha-beta, tau, and P-tau proteins) did not differ among the three groups.
The E/C/ALA group did show a 19% reduction in the oxidative stress CSF biomarker F2-isoprostane, but the authors expressed concern at the rapid decline in cognitive function in this group, as assessed using the Mini-Mental State Examination (MMSE).
"It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in AD. The more rapid MMSE score decline raises a caution and indicates that cognitive performance would need to be assessed if a longer-term clinical trial of this antioxidant combination is considered," they conclude.
They also note that while the findings suggest CoQ was safe and well tolerated, the absence of any impact on the CSF biomarkers would suggest that at the dose tested in this trail, CoQ does not affect oxidative stress or the progress of neurodegeneration.
Antioxidant supplements don't appear to have an impact on cerebrospinal fluid (CSF) biomarkers related to Alzheimer's disease, a clinical trial determined.
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.
First author Dr Douglas R. Galasko, from the Department of Neuroscience at the University of California San Diego, and colleagues describe how they tested for the effects of a combination of vitamin E, vitamin C and alpha-lipoic acid (E/C/ALA) on levels of CSF biomarkers.
Alzheimer's disease is characterized by an abundance of beta-amyloid protein plaques that clog up the spaces between brain cells and tau-based neurofibrillary tangles that clog up the insides of brain cells. Certain proteins in spinal fluid relate to this amyloid and tau pathology and serve as reliable biomarkers for the disease.
Metabolic reactions in the body produce free radicals that interact with other molecules to cause oxidative damage to proteins, membranes and genes. This influences the aging process and is also linked to disease, including cancer and Alzheimer's. In fact, oxidative damage in the brain is widespread among people with Alzheimer's disease.
The body defends against oxidative damage by producing antioxidants to mop up free radicals. Genes, environment and lifestyle (eg diet, smoking, exercise) determine how well it does this.
Increasing intake of antioxidants can boost the body's ability to defend itself against oxidative damage, and Galasko and colleagues write that some observational studies have suggested that a diet rich in antioxidants can reduce the risk of Alzheimer's disease, but randomized clinical trials have shown mixed results.
For their study, Galasko and colleagues looked at changes in CSF biomarkers related to Alzheimer's disease and oxidative stress, cognition and function in 78 patients from the Alzheimer's Disease Cooperative Study (ADCS) Antioxidant Biomarker study.
The patients were placed in three groups.
One group took 800 IU per day of vitamin E (alpha-tocopherol), plus 500 mg per day of vitamin C, plus 900 mg per day of alpha -lipoic acid (E/C/ALA). Another group took 400 mg of the popular antioxidant coenzyme Q (CoQ) three times a day, while the third group was given a placebo.
66 of the patients provided serial CSF samples that were adequate for analysis during the trial, which lasted for 16 weeks.
The results showed that changes in the CSF biomarkers for the amyloid and tau proteins that are related to Alzheimer's disease (alpha-beta, tau, and P-tau proteins) did not differ among the three groups.
The E/C/ALA group did show a 19% reduction in the oxidative stress CSF biomarker F2-isoprostane, but the authors expressed concern at the rapid decline in cognitive function in this group, as assessed using the Mini-Mental State Examination (MMSE).
"It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in AD. The more rapid MMSE score decline raises a caution and indicates that cognitive performance would need to be assessed if a longer-term clinical trial of this antioxidant combination is considered," they conclude.
They also note that while the findings suggest CoQ was safe and well tolerated, the absence of any impact on the CSF biomarkers would suggest that at the dose tested in this trail, CoQ does not affect oxidative stress or the progress of neurodegeneration.
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