Best Antioxidants to Prevent Age-Related Dementia Identified?

Megan Brooks

May 05, 2022

Higher levels of specific carotenoid antioxidants in blood may help guard against age-related dementia, new research suggests.

Investigators found that individuals with the highest serum levels of lutein+zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than their peers with lower levels of these antioxidants.

Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.

"Antioxidants may help protect the brain from oxidative stress, which can cause cell damage," first author May A. Beydoun, PhD, MPH, with the National Institute on Aging (NIA), said in a news release. 

"This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk," NIA scientific director Luigi Ferrucci, MD, told Medscape Medical News.

"Blood test results may be more representative of the actual antioxidant level than a person's report of what kind of foods they regularly consume," Ferrucci added.

The study was published online today in Neurology.

Reduced Dementia Risk

The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer's disease (AD) and all-cause dementia.

The researchers analyzed data from 7283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.

They found serum levels of lutein+zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.

For lutein+zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% CI, 0.87 - 0.99, P = .037). This association was attenuated somewhat after adjusting for socioeconomic status.

Serum levels of beta-cryptoxanthin showed a "strong" inverse relationship with all-cause dementia in age- and sex-adjusted models.

For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80 - 0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80 - 0.93, P = .001).

This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.

No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.

Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers note.

"This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein+zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality," said Ferrucci.

"Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake — through the diet and/or supplements — to promote brain health and healthy aging," he added.

An Important Step Forward

In an accompanying editorial, Babak Hooshmand, MD, PhD, MPH, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, Sweden, note that while nutrition and dietary components are "potential targets" for dementia risk reduction, observational studies to date have reported "inconsistent findings."

This study is "an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components," they write.

The findings are "challenging," they add, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.

However, clinical trials of antioxidant supplementation have been mainly "disappointing" and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Hooshmand and Kivipelto note.

They add that the study contributes to the belief that antioxidants don't act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.

"A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye," they conclude.

The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Beydoun, Ferrucci, and Hooshmand report no relevant disclosures. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.

Neurology. Published online May 5, 2022. Abstract, Editorial

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