Higher Serum Lutein and Zeaxanthin Levels Associated with a Lower Risk of All-Cause Dementia

by | Jul 5, 2022 | 2022, Alzheimer's Disease, Brain Health, Cognitive Health, Lutein, Zeaxanthin

Written by Taylor Woosley, Staff Writer. Study findings using data from the NHANES III Survey (1988-1994) show that serum lutein+zeaxanthin was associated with a reduced risk of all-cause dementia, with an inverse relationship being noted between serum β-cryptoxanthin and all-cause dementia.  

aging woman with nurseDementia is a syndrome characterized by decline in cognitive domains, beyond that expected in normal aging, and affects more than 50 million people worldwide 1. Alzheimer’s disease (AD) is the most common kind of dementia and is associated with deterioration of higher functions accompanied by neuropathology 2. AD is a complex and progressive neurodegenerative disease affecting about 5% of the population over 65 years old 3. Two major neuropathological hallmarks of AD are the aggregation of amyloid-β (Aβ) and phosphorated microtube-associated protein tau which leads to the formation of neurofibrillary tangles and senile plaques 4.

Oxidative stress, a pathophysiological mechanism in cognitive impairment, can be influenced by nutrition 5. Phytonutrients, chemical compounds produced by plants such as flavonoids and carotenoids, have been studied for their potential neuroprotective benefits 6. Certain plant carotenoids, for example, lutein and zeaxanthin, have been described to inhibit AChE and BChE, traverse the blood-brain barrier, and possess robust antioxidant properties 7. Previous studies with plasma measures of antioxidants have associated higher levels of lutein, zeaxanthin, and β-carotene to better cognitive function and dementia risk 8.

Beydoun et. al conducted an observational study using data collected from the Third National Health and Nutrition Examination Survey (NHANES III) which comprised a cross-sectional sample representative of the US civilian population obtained between 1988 and 1994. Subject inclusion consisted of being 45-90 years of age with available biomarkers and linkage, resulting in an analytic sample of 7,283. A further restricted sample was conducted using participants (n=3,618) aged ≥65 years at baseline. Most subjects experienced a follow-up time of an average of 16 to 17 years, with up to 26 years of follow-up for certain subjects.

Cases of AD and all-cause dementia were identified using information from the CMS Chronic Condition Data Warehouse. Measurements of serum levels of vitamin A, vitamin E, retinyl esters, and carotenoids were completed by isocratic high-performance liquid chromatography, with additional vitamin C measurements. Covariates such as age at baseline, sex, race, urban-rural residence, and education level were added in multivariable models. Furthermore, lifestyle and health-related covariates like smoking, diet, alcohol use, and physical activity were also measured, along with a single 24-hour dietary recall to assess participants nutrient intake. Significant results of the study are as follows:

  • Individual lutein and zeaxanthin plasma concentration was associated with reduced risk of all-cause dementia in the 65+ baseline age group, even after adjusting for lifestyle factors (HR 0.93, 95% CI 0.87-0.99, p = 0.037).
  • A significant inverse relationship was detected between serum β-cryptoxanthin and all-cause dementia in both age groups for the age and sex-adjusted models (HR 0.86, 95% CI 0.80-0.93, p < 0.001 for 45+; HR 0.86, 95% CI 0.80-0.93, p = 0.001 for 65+).
  • In fully adjusted models, antagonistic interactions were observed between serum vitamin A and α-carotene vs. all-cause dementia (β±standard error of estimate [SEE] +0.039 ± 0.016, p = 0.017); vitamin A and α-carotene vs AD dementia (β±SEE +0.080 ± 0.016, p < 0.001); vitamin A and β-carotene vs AD incidence (β±SEE +0.088 ± 0.021, p < 0.001); and vitamin E and lycopene vs AD incidence (β±SEE +0.078 ± 0.022, p = 0.001).

Study findings suggest an inverse association between incident all-cause dementia and serum lutein+zeaxanthin and β-cryptoxanthin levels. Study limitations include lack of use of a formal set of cognitive performance tests to diagnose dementia at baseline of the study, the lack of information regarding flavonoid levels in participants, and the potential for regression dilution due to longer follow-up periods. Future studies should include time-dependent exposures and randomized trials to better understand the neuroprotective effects of supplementing with carotenoids.

Source: Beydoun, May A., Hind A. Beydoun, Marie T. Fanelli-Kuczmarski, Jordan Weiss, Sharmin Hossain, Jose Atilio Canas, Michele Kim Evans, and Alan B. Zonderman. “Association of serum antioxidant vitamins and carotenoids with incident Alzheimer disease and all-cause dementia among US adults.” Neurology 98, no. 21 (2022): e2150-e2162.

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Posted July 5, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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