Have the best antioxidants been identified to prevent age-related dementia?

New research suggests that higher levels of specific carotenoid antioxidants in the blood may help protect against age-related dementia.

The researchers found that people with higher 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 cabbage, spinach, broccoli and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines and persimmons.

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

“This is the first nationally representative study to analyze blood levels of antioxidants in relation to the risk of dementia,” said NIA Scientific Director Luigi Ferrucci, MD. Medscape medical news.

“The results of blood tests may be more representative of the actual level of antioxidants than a person’s report on what type of food they usually consume,” Ferrucci added.

The study was published online today at Neurology.

Reduced risk of dementia

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

The researchers analyzed data from 7,283 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 that serum lutein + zeaxanthin levels were associated with a reduced risk of dementia for all causes among people aged 65 and over in lifestyle-adjusted models.

For lutein + zeaxanthin, each increase in standard deviation (SD) (approximately 15.4 µmol / liter) was associated with a 7% decrease in the risk of dementia (hazard ratio). [HR] 0.93; 95% CI, 0.87 – 0.99, P = 0.037). This association weakened somewhat after adjusting to the socioeconomic status.

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

For beta-cryptoxanthin, each increase in SD (approximately 8.6 µmol / liter) was associated with a 14% reduction in the risk of dementia in people aged 45 years or older (HR, 0.86; %, 0.80 – 0.93, P <0.001) and 65 years or older (HR, 0.86; 95% CI, 0.80 - 0.93, P = 0.001).

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

No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully fitted 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 an antioxidant at higher levels. low of the other, the researchers point out.

“This analysis from an observational study found that the most important carotenoids to potentially protect the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causation,” Ferrucci said.

“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 required level of antioxidant intake, through diet and / or supplements, to promote brain health and healthy aging. ” added.

An important step forward

In an attached editorial, Babak Hooshmand, MD, PhD, MPH, and Miia Kivipelto, MD, PhD, with the Karolinska Institute, Stockholm, Sweden, note that while nutrition and dietary components are “potential targets” for reducing the risk of dementia, observational data studies have reported “inconsistent findings.”

This study is “an important step toward exploring the complex relationship between antioxidants and dementia because it takes into account factors that could possibly influence associations and considers the 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 could have beneficial effects in preventing dementia.

However, clinical trials of antioxidant supplements have been primarily “disappointing,” and a recent Cochrane review found a lack of evidence for the use of supplements to preserve cognitive function or prevent dementia, Hooshmand and Kivipelto point out.

They add that the study contributes to the belief that antioxidants do not act independently of each other or other factors, including socioeconomic status and lifestyle, in mediating the risk of dementia.

“Careful examination of the evidence is required to determine how antioxidants influence the complex pathology of dementia, because it appears to be more than it appears,” 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 do not report any relevant disclosures. Kivipelto has supported the advisory boards of Combinostics, Roche and Biogen.

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

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