Supplement Combo Boosts Working Memory in Older People

This combination consists of compounds commonly found in foods.


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An open-access human study published in Clinical Nutrition has found that a combination of supplements is beneficial for working memory.

Identifying the dietary compounds

Specific types of eating patterns have been associated with improved memory and cognition. The authors highlight some of the specific dietary components that selectively accumulate in the brain with biochemical effects, including omega-3 fatty acid, vitamin E, and xanthophyll carotenoids [1-5].

Xanthophyll carotenoids are oxygen-carrying plant-based pigments with nutraceutical properties. For this study, the researchers chose to use lutein, zeaxanthin, and meso-zeaxanthin xanthophyll carotenoids, which can be found in many edible plants that are green, yellow, and yellow-orange and in some animal-based foods as well. Eggs and spinach are both excellent sources of lutein and zeaxanthin.

A long, placebo-controlled trial

This randomized, controlled, two-year-long trial included participants taking a combination supplement or placebo supplement of sunflower oil. The combination supplement contained 1 gram of fish oil, 22 milligrams of xanthophyll carotenoids, and 15 milligrams of vitamin E.


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The combination and placebo supplement were identical in color and size, and the participants were instructed to take two capsules at a time alongside a meal. Supplements that contain fat-soluble components, such as the nutrients chosen in this study, are digested more efficiently when consumed with a meal that contains fat.

Participants checked in at the Nutrition Research Centre Ireland at the beginning of the study. They also checked at one year and again at the end of the study. Fifty out of sixty participants completed the study. To be included in the study, participants needed to be 65 years and older; have no personal or family history of memory loss, no diagnosis or symptoms of dementia, and no history of stroke; and could not currently take cognitive enhancers, supplements containing fish/cod liver, or other carotenoid supplements.

Cognitive assessments were measured with MoCA version 7.1 and RBANS form A. The MoCA is a screening used to detect cognitive impairment, while the RBANS was used as a diagnostic tool to detect cognitive improvement or decline.

More carotenoids, better memory

After 12 and 24 months, the supplement group had accumulated significant amounts of these carotenoids as measured in the skin, blood serum, and macular pigment optical volume (MPOV). MPOV is a non-invasive biomarker that determines the presence of the xanthophyll carotenoids lutein, zeaxanthin, and meso-zeaxanthin in the brain, as they also accumulate in the central retina (as “macular pigments”) after dietary consumption. In the plasma, DHA and EPA levels also improved. However, there was no change in the biomarker that the researchers used to measure vitamin E, serum alpha-tocopherol.

Using correlation statistics, the authors observed after 24 months that the participants with higher MPOV scores and participants with higher blood concentrations of lutein, meso-zeaxanthin, DHA, or EPA had fewer errors in the working memory task compared to participants with lower levels of these biomarkers.


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Finally, the supplement group also out-performed the placebo group on the working memory tasks over time. Additionally, higher levels of omega-3 fatty acids in plasma were correlated with improvements on the memory task.


These results support a biologically plausible rationale whereby these nutrients work synergistically, and in a dose-dependent manner, to improve working memory in cognitively healthy older adults. Increasing nutritional intake of carotenoids and ω-3FAs may prove beneficial in reducing cognitive decline and dementia risk in later life.

This study was limited by its small sample size and limited demographic breadth, and the authors disclosed a conflict of interest in that they are consultants for supplement companies. It would be great to see this study done at other medical and research centers to confirm this research and determine if this is truly a promising combination supplement in helping to prevent cognitive decline and improve nutrition status later in life.


This article is only a very brief summary, is not intended as an exhaustive guide, and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use or any product or supplement vendor, and all discussion here is for scientific interest.

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[1] Singh M. (2005). Essential fatty acids, DHA and human brain. Indian journal of pediatrics, 72(3), 239–242.

[2] Weiser, M. J., Butt, C. M., & Mohajeri, M. H. (2016). Docosahexaenoic Acid and Cognition throughout the Lifespan. Nutrients, 8(2), 99. https://doi.org/10.3390/nu8020099


[3] Craft, N. E., Haitema, T. B., Garnett, K. M., Fitch, K. A., & Dorey, C. K. (2004). Carotenoid, tocopherol, and retinol concentrations in elderly human brain. The journal of nutrition, health & aging, 8(3), 156–162.

[4] Johnson, E. J., Vishwanathan, R., Johnson, M. A., Hausman, D. B., Davey, A., Scott, T. M., Green, R. C., Miller, L. S., Gearing, M., Woodard, J., Nelson, P. T., Chung, H. Y., Schalch, W., Wittwer, J., & Poon, L. W. (2013). Relationship between Serum and Brain Carotenoids, a-Tocopherol, and Retinol Concentrations and Cognitive Performance in the Oldest Old from the Georgia Centenarian Study. Journal of aging research, 2013, 951786. https://doi.org/10.1155/2013/951786

[5] Lieblein-Boff, J. C., Johnson, E. J., Kennedy, A. D., Lai, C. S., & Kuchan, M. J. (2015). Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain. PloS one, 10(8), e0136904. https://doi.org/10.1371/journal.pone.0136904

About the author


Tovah has been a Registered Dietitian Nutritionist (RDN) for the past 11 years in clinical, research, teaching, community, and industry roles. Her dissertation work was focused on nutritional and behavioral neuroscience approaches for chronic disease prevention. She was a writer for Lifespan.io from 2021-22 and is still an active volunteer with the org.