Dementia Risk Tied to Antioxidant Levels

Dementia risk was linked with blood levels of certain antioxidants, an observational study showed.

Higher serum levels of lutein+zeaxanthin and beta-cryptoxanthin — two types of carotenoids — were tied to a lower risk of incident dementia, reported May Beydoun, PhD, MPH, of the NIH National Institute on Aging in Baltimore, Maryland, and colleagues, in Neurology.

Findings were attenuated in adjusted analyses, suggesting socioeconomic status, lifestyle, and diet quality may mediate the associations.

When oxidative stress occurs at an abnormally high level, consuming antioxidants may help protect cells of the body, including brain cells, from damage, Beydoun noted. “Carotenoids, which are the pigments found in orange and yellow plants, are converted by the body into vitamin A. We found that the most important carotenoids in potentially protecting the brain may be lutein+zeaxanthin and beta-cryptoxanthin,” she told MedPage Today.

“Unlike other studies, we did not analyze levels of dietary intakes of antioxidants or carotenoids. Instead, we analyzed levels of antioxidants and carotenoids in the blood,” Beydoun pointed out.

“This is the first nationally representative study to do so in relation to dementia risk,” she said. “This may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume. That simple fact may explain why results from dietary comparison studies for the development of dementia have been mixed.”

While nutrition and diet components may be potential dementia risk targets in the future, observational studies so far have shown inconsistent findings, noted Babak Hooshmand, MD, PhD, MPH, and Miia Kivipelto, MD, PhD, both of the Karolinska Institute in Stockholm, in an accompanying editorial.

“For example, dietary total carotenoid consumption and in particular lutein+zeaxanthin and lycopene were associated with reduced incidence of Alzheimer’s disease and its neuropathology among 927 older adults from the Rush Memory and Aging Project who were followed up over 7 years,” Hooshmand and Kivipelto wrote.

However, several longitudinal studies about dietary components and dementia have reported null findings, they observed. “Possible explanations for the discrepancies are heterogeneities in study designs and populations, differences in antioxidant status and dietary habits, and different consideration of potential confounders,” the editorialists wrote.

Beydoun and colleagues used data from 7,283 participants in the third National Health and Nutrition Examination Survey (NHANES 1988-1994), linking that information with Centers for Medicare & Medicaid Services records to identify incident dementia cases for up to 26 years.

Participants were ages 45-90 at baseline and mean followup was 16-17 years. At baseline, participants were dementia-free and had a physical exam, interview, and blood draw.

Findings included:

• Among people ages 65 and older, serum lutein+zeaxanthin was associated with reduced risk of all-cause dementia in models adjusted for lifestyle (per SD, HR 0.93, 95% CI 0.87-0.99, P=0.037) and socioeconomic status (HR 0.92, 95% CI 0.86-0.93, P=0.013).
• Serum beta-cryptoxanthin showed an inverse relationship with all-cause dementia in age-and sex- adjusted models of people 45 and older (per SD, HR 0.86, 95% CI 0.80-0.93, P<0.001) and 65 and older (HR 0.86, 95% CI 0.80-0.93, P=0.001). This association also was seen a model adjusted for socioeconomic status (HR 0.89, 95% CI 0.82-0.96, P=0.006), but was less strong in subsequent models.
• No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in fully adjusted models. Antagonistic interactions were seen for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting protective effects of one antioxidant at lower levels of the other.

Green, leafy vegetables like kale, spinach, and broccoli are sources of lutein+zeaxanthin, while beta-cryptoxanthin is found in fruits like oranges, papaya, and tangerines.

“The take-home message is that a healthy diet rich in carotenoids and antioxidants from dark leafy greens and orange-pigmented fruits with or without antioxidant supplements may reduce the risk of developing dementia,” Beydoun said. “But the only way to prove the connection between carotenoids and brain protection health is with a long-term, randomized clinical trial with antioxidant supplements to see whether fewer people develop dementia over time.”

“Also, importantly, it is not yet known what levels of antioxidants we need to consume each day through food, beverages, and supplements to promote healthy aging of the brain,” she added. “More research is needed to establish the necessary amount of antioxidants to promote brain health and healthy aging.”

A limitation of the study is that antioxidant levels were based on one measurement and may not reflect lifetime habitual intakes, the researchers noted. Reverse causality also may have influenced the findings.