Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study

Morris, Martha Clare; Evans, Denis A.; Bienias, Julia L.; Tangney, Christine C.; Bennett, David A.; Aggarwal, Neelum T.; Wilson, Robert S.; Scherr, Paul A.

doi:10.1001/jama.287.24.3230

Cited by 606 publications

(397 citation statements)

References 37 publications

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“…(25,67,84) A number of studies have shown that vitamin E intake from food sources is associated with beneficial outcomes in heart disease, (23) colon cancer, (85) and Alzheimer's disease. (24) It is noteworthy that over 80% of fats and oils used in the US are comprised of soybean oil. (10) High consumption of soybean oil is associated with increased serum gamma-tocopherol levels.…”

Section: Discussionmentioning

confidence: 99%

Effects of vitamin E on bone turnover markers among US postmenopausal women

Hamidi

Corey

Cheung

2012

Journal of Bone and Mineral Research

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Increased oxidative stress and inflammation resulting from aging and declining estrogen levels can lead to increased bone loss in postmenopausal women. Alpha-tocopherol and gamma-tocopherol, the two predominant isomers of vitamin E, have antioxidant and anti-inflammatory properties, but their effects on bone metabolism have not been well studied in humans. We examined the associations between dietary and total (diet and supplements) alpha-tocopherol intake, serum alpha-tocopherol and gamma-tocopherol levels and their ratio, and bone turnover markers (BTMs) among postmenopausal women aged !45 years. We used cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002. Multiple regression models with adjustments for relevant confounders were used to examine the associations between intake and serum levels of tocopherols, and serum bone-specific alkaline phosphatase (BAP), a biomarker of bone formation, and urinary N-telopeptides/creatinine (uNTx/Cr), a biomarker of bone resorption. The study sample included 497 postmenopausal women who were not taking estrogen, steroids, or osteoporosis medications, were free from kidney and liver disease, cancer, and rheumatoid arthritis, and were fasting >9 hours prior to examination. Participants had a mean age of 65.5 AE 0.6 years and over 45% used vitamin E (alpha-tocopherol) supplements in the past month. Vitamin E supplement users had significantly lower serum gamma-tocopherol, higher serum alpha-tocopherol levels, and higher ratio of serum alpha-tocopherol to gamma-tocopherol than nonusers. High serum gamma-tocopherol levels and low ratio of serum alpha-tocopherol to gamma-tocopherol were associated with increased BAP levels (p < 0.01 for both). There were no associations between any of the vitamin E variables and uNTx/Cr. In conclusion, we hypothesize that gamma-tocopherol may uncouple bone turnover, resulting in more bone formation than resorption. Vitamin E supplements in the form of alpha-tocopherol suppress serum gamma-tocopherol levels and may have negative effects on bone formation. Further research is needed to investigate the potential anabolic effect of gamma-tocopherol from food sources on bone. ß

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Section: Discussionmentioning

confidence: 99%

Effects of vitamin E on bone turnover markers among US postmenopausal women

Hamidi

Corey

Cheung

2012

Journal of Bone and Mineral Research

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“…Some studies of antioxidant supplements have found no protective effect [22], or a significant protective effect only with vitamin C [2], or only when both vitamins E and C are taken together [6]. Regarding dietary intake, studies have found a protective effect with intake of vitamin E [4,5] or vitamin C [4], whereas others have not found an effect [23,24].…”

Section: Discussionmentioning

confidence: 99%

“…Data from a handful of cohort studies suggest that the risk of AD may be reduced in people with a high dietary or supplemental intake of antioxidants [2][3][4][5][6]. Furthermore, low serum levels of B vitamins [7] and hyperhomocysteinemia [8] (which can be caused by B-group vitamin deficiencies), have been associated with an increased risk of AD.…”

Section: Introductionmentioning

confidence: 99%

Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging

Corrada

Kawas

Hallfrisch

et al. 2005

Alzheimer's & Dementia

137

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Background-Study findings have suggested an association between Alzheimer's disease (AD) risk and several vitamins and have speculated about their use as preventive agents. Here, we examine whether total intake (intake from diet plus supplements) of antioxidant vitamins (E, C, carotenoids) and B vitamins (folate, B 6 , and B 12 ) is associated with a reduced risk of AD.Methods-Participants were 579 nondemented elderly volunteers from the Baltimore Longitudinal Study of Aging who completed dietary diaries and recorded supplement intake for a 7-day period. Cox regression was used to estimate the relative risk (RR) of AD associated with total vitamin intake categorized into levels above or below the Recommended Dietary Allowance (RDA).Results-After a mean follow-up of 9.3 years, AD developed in 57 participants. Higher intake of folate (RR, 0.41; 95% confidence interval [CI], 0.22 to 0.76), vitamin E (RR, 0.56; 95% CI, 0.30 to 1.06), and vitamin B 6 (RR, 0.41; 95% CI, 0.20 to 0.84) were associated individually with a decreased risk of AD after adjusting for age, gender, education, and caloric intake. When these 3 vitamins were analyzed together, only total intake of folate at or above the RDA (RR, 0.45; 95% CI, 0.21 to 0.97) was associated with a significant decreased risk of AD. No association was found between total intake of vitamins C, carotenoids, or vitamin B 12 and risk of AD.Conclusions-These findings suggest that total intake of folate at or above the RDA is associated with a reduced risk of AD. Additional studies are necessary to further investigate whether folate or other(s) unmeasured factor(s) may be responsible for this reduction in risk.

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“…These include, but are not limited to, flavonoids (e.g., quercetin, morin, or baicalein), β-carotene, curcumin, zinc, folic acid, and selenium. Most of these showed little promise as an AD therapeutic on their own, but when combined together in formulations they improved cognitive function in transgenic AD mice and reduced oxidative stress [129,130].…”

Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

2015

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Alzheimer's disease (AD) has a complex and progressive neurodegenerative phenotype, with hypometabolism and impaired mitochondrial bioenergetics among the earliest pathogenic events. Bioenergetic deficits are well documented in preclinical models of mammalian aging and AD, emerge early in the prodromal phase of AD, and in those at risk for AD. This review discusses the importance of early therapeutic intervention during the prodromal stage that precedes irreversible degeneration in AD. Mechanisms of action for current mitochondrial and bioenergetic therapeutics for AD broadly fall into the following categories: 1) glucose metabolism and substrate supply; 2) mitochondrial enhancers to potentiate energy production; 3) antioxidants to scavenge reactive oxygen species and reduce oxidative damage; 4) candidates that target apoptotic and mitophagy pathways to either remove damaged mitochondria or prevent neuronal death. Thus far, mitochondrial therapeutic strategies have shown promise at the preclinical stage but have had little-to-no success in clinical trials. Lessons learned from preclinical and clinical therapeutic studies are discussed. Understanding the bioenergetic adaptations that occur during aging and AD led us to focus on a systems biology approach that targets the bioenergetic system rather than a single component of this system. Bioenergetic system-level therapeutics personalized to bioenergetic phenotype would target bioenergetic deficits across the prodromal and clinical stages to prevent and delay progression of AD.

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Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study

Cited by 606 publications

References 37 publications

Effects of vitamin E on bone turnover markers among US postmenopausal women

Effects of vitamin E on bone turnover markers among US postmenopausal women

Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

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