December 2017 Issue

Nutrients for a Sharp Memory
By Judith C. Thalheimer, RD, LDN
Today's Dietitian
Vol. 19, No. 12, P. 24

Research supports a variety of nutrients and food components that protect cognitive function.

Nearly everyone has walked into a room and forgotten what he or she went in there for, or has had trouble recalling an obvious word, and worried that his or her brain may not be as sharp as it once was. "My private clients, both young and old, express concern about preserving their memory," says Jennifer McDaniel, MS, RDN, CSSD, LD, a spokesperson for the Academy of Nutrition and Dietetics. "I believe many underestimate the power of dietary choices in supporting brain health."

The brain, like the cardiovascular system, depends on good blood flow for optimal functioning.1 Heart-healthy lifestyle choices such as regular physical activity and a healthful dietary pattern are, therefore, good ways to keep the brain healthy and the memory sharp. "What's good for the heart is good for the head," McDaniel says. The heart-healthy Mediterranean-style eating pattern, for example, is linked to better cognitive function, memory, and alertness in numerous studies. The MIND diet, a variation of the Mediterranean diet that specifically targets brain health, adds an emphasis on certain foods such as green leafy vegetables and berries that have been linked (or contain components that in studies have been linked) with brain benefits. (See "Food for Thought: The MIND Diet — Fighting Dementia With Food" in the September 2015 issue of Today's Dietitian.) But what are some particular nutrients or food components that stand out for their brain-boosting powers? Research is inconclusive to date, but a few promising nutrients are detailed below.

Omega-3 Fatty Acids
The omega-3 family of polyunsaturated fatty acids (PUFAs) plays several important roles in brain structure and function, and there's clinical evidence suggesting that dietary deficiency in these PUFAs can have adverse cognitive effects.2 In addition, "There's solid evidence from observational studies linking omega-3 fatty acid intake to cognitive benefits," says Ondine van de Rest, MSc, PhD, an assistant professor in the division of human nutrition at Wageningen University in the Netherlands who's done extensive work on nutrition and cognition. Numerous epidemiologic studies have found that high intake of PUFA-rich fish is associated with positive cognitive function and inversely associated with development and progression of dementia.2 In one study, elderly subjects who consumed fish or seafood even once per week exhibited a significantly lower risk of developing dementia in the seven-year follow-up period.2

The long-chain omega-3 DHA, found in fish, shellfish, and algae, but especially prevalent in oily fish such as salmon, mackerel, herring, anchovies, menhaden, and sardines, is especially important to brain function.2 Since the body doesn't make DHA efficiently, humans are dependent on dietary sources, and it appears the typical Western diet is falling short.2 According to one study, less than one-half of women consume the recommended dietary allowance.2

Despite these promising correlations, cause and effect has yet to be definitively demonstrated. "So far it has been hard to replicate these epidemiologic results in randomized controlled intervention studies, which are needed to establish a causal relationship," van de Rest says. "Intervention studies to date show modest results, if any, and only in specific groups of mild cognitively impaired individuals, not in those who are still cognitively healthy."

Research methodology may play a role in this discrepancy. "Some clinical studies that found no beneficial effects from omega-3 supplementation let participants in the control group eat up to three fish meals a week," says Maggie Moon, MS, RDN, author of The MIND Diet: A Scientific Approach to Enhancing Brain Function and Helping Prevent Alzheimer's and Dementia. "The amount of omega-3s in the fish would be enough to nullify any difference between the groups."

When it comes to brain health, avoiding saturated and trans fat may be as important as consuming polyunsaturated omega-3 fats. According to a 2014 review, laboratory, animal, and prospective epidemiologic studies support the hypothesis that high intake of saturated or trans fatty acids increases the risk of dementia.3 Moreover, the Chicago Health and Aging Project found that the people in the upper quintile for saturated fat consumption had a two-fold increased risk of Alzheimer's disease compared with those in the lowest quintile.2 Not all studies are in agreement, but Moon again points to methodology as a likely confounding factor. "When you've got good methodology and control for the type of fat, the relationship between saturated fat and cognitive decline is clear," Moon says. "They rise together."

Lutein
Lutein, a yellow-pigmented carotenoid found in egg yolk, avocado, and dark leafy greens such as spinach and kale, is another nutrient found to aid in brain health and preserve memory. Elizabeth Johnson, PhD, an antioxidant researcher with the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, has been involved in extensive research on lutein. "Lutein is selectively taken up into the macula of the retina, where it's believed to be important for eye health," Johnson says. "To get to the retina, it needs to cross the blood-brain barrier." Research by Johnson and her colleagues found that lutein is the major carotenoid in the brain, and that brain tissue levels of lutein are related to cognition, including memory.4

In a small, double-blinded placebo-controlled randomized trial, researchers gave supplements containing 10 mg lutein plus 2 mg zeaxanthin (another carotenoid found in the retina) per day to healthy older adults for 12 months and found improved cognitive function in the study population compared with the placebo group.5 "That's the amount or lutein found in about 2 oz of cooked spinach," Johnson says. "Unfortunately, the average American consumes only around 1 to 2 mg of lutein per day."

Notably, one study showed that even greater improvements in cognitive function were found when lutein was paired with the omega-3 fatty acid DHA.6 "No nutrient works in isolation," Johnson says. "This study demonstrates that lutein and DHA are working together, and that's how food works. When we promote better food selection, we promote better health."

Vitamins
Epidemiologic studies show that consumption of adequate vitamins and minerals (dietary or supplemental) is associated with lower risk of developing cognitive deficits.7 The B vitamins and vitamins E, C, and D specifically have been identified as playing important roles in maintaining normal brain function. Several of these vitamins (such as thiamine and vitamin E) are constituents of neuronal membranes, and others (including B6, B12, and vitamin C) are implicated in tasks such as the synthesis and functioning of neurotransmitters. Members of the B vitamin family and vitamin C also are essential to energy production in the brain.7 The antioxidant power of vitamins C and E also may be important for reducing oxidation in the brain. Given their importance in neuronal function, these micronutrients have been studied as a way to help neurons cope with aging, with particular emphasis on vitamin E and the B vitamins.

Vitamin E
The antioxidant vitamin E is found in whole grains, nuts, seeds, dark-colored fruits such as blueberries and blackberries, avocados, dark leafy greens, bell peppers, and vegetable oils.8 "Results of the research on vitamin E and the brain have been conflicting," Moon says, "but controlling for initial serum levels of the vitamin clears up the discrepancy. A lot of the data on supplementation did not take into account baseline blood levels. People who start at a deficit do see improvement in brain-related symptoms and cognitive ability. For those already at an adequate level, adding more isn't going to help."

A study published in JAMA in 2014 found that, among patients with mild to moderate Alzheimer's disease, those whose diets were supplemented with 2,000 IU per day of the vitamin E form α-tocopherol showed slower functional decline compared with the placebo group.9 Unfortunately, taking more than 1,000 IU of vitamin E supplements per day may be unsafe, particularly for people with CVD. Vitamin E supplementation is especially risky for those on blood thinners, and it also may increase prostate cancer risk.8

"There has been controversy around vitamin E supplements but never around vitamin E-rich food intake," Moon says. Fortunately, it shouldn't be difficult to get enough vitamin E from food, and doing so may provide additional benefits. "Food sources provide a mix of all eight forms of vitamin E, while supplements have just one or two," Moon says. "Nutrients act synergistically in the body, and although we don't know how the different forms of vitamin E interrelate, getting all eight forms in their natural concentrations is the best bet."

B Vitamins
Although supplementation with B vitamins hasn't been shown unequivocally to improve brain function or symptoms of memory loss, the important role these vitamins play in the brain raises some interesting possibilities.10 For example, deficiency in vitamin B12, found exclusively in animal products, is known to lead to dementialike symptoms, which can be reversed by raising B12 levels. Low levels of both B12 and folate together have been associated with a significantly increased risk of Alzheimer's disease.7 One possible link between these vitamins and dementia is their role in the metabolism of the amino acid homocysteine. Clinical research shows that people with cognitive impairment have significantly higher plasma levels of homocysteine, and insufficient levels of B6, B12, folate, thiamine, and riboflavin are implicated in high homocysteine levels and cognitive deficits.7

Many studies on the role of B vitamins in brain health to date are inconclusive and conflicting, but numerous methodological issues come into play. "Some studies aren't very sensitive or fail to take into account baseline levels of the vitamin," Moon says. It may be necessary to consider how nutrients work together rather than studying them in isolation. Recent preliminary research, for example, suggests that B vitamin treatment is effective in slowing cognitive decline only when omega-3 fatty acid levels are normal.11

"You can't fix something that's not broken," Moon says. "If someone has low vitamin status, raising those levels through diet or supplementation could be beneficial."

Polyphenols
Many bioactive compounds found in plants have been examined for their role in brain health. The class of compounds known as polyphenols, in particular, is associated in population-based studies with better performance in cognitive abilities and lower risk of cognitive decline in older persons.2 Found in fruits, vegetables, tea, wine, juices, and some herbs, polyphenols have antioxidant properties and may have other beneficial effects in the brain, including neuroprotective and anti-inflammatory actions.2 Much has been written about the positive effects of berries on brain health, largely due to their high concentration of polyphenol flavonoid compounds called anthocyanins. Research on other compounds from this class of phytochemicals also is yielding promising results.

Curcumin
The polyphenolic compound curcumin lends its yellow pigment to turmeric. Preclinical studies suggest curcumin has antioxidant, anti-inflammatory, and neuroprotective effects.12 "India has one of the lowest rates of Alzheimer's disease," McDaniel says. "The curcumin in their traditional curries has been shown to help reduce inflammation in the brain and reduce oxidative stress." A large population-based study found that healthy elderly Asians who frequently consumed curcumin-rich curries scored significantly better on tests of cognitive function than those who ate curries infrequently.2 While a six-month, randomized placebo-controlled double-blinded clinical study of curcumin in persons with progressive cognitive decline and memory issues didn't show improvements in brain function scores, another study that provided supplementation with 400 mg curcumin found both short- and long-term positive effects on memory and mood in healthy older adults.2 A 2017 review in the journal Neural Plasticity concludes that, while curcumin may benefit the brain and cognitive function during aging, no clinical trials to date provide conclusive evidence that long-term curcumin consumption is effective for prevention or treatment of cognitive decline with aging. The review authors point to limited bioavailability as a significant limitation in studies and interventions of this promising phytochemical.2

Resveratrol
A polyphenolic compound found in grapes, wine, peanuts, and some berries, resveratrol has significant free radical scavenging capabilities.2,13 Animal studies have suggested that resveratrol might be beneficial for brain health, but few clinical trials have been completed.13 One small-scale, randomized placebo-controlled double-blinded trial that added concord grape juice to the diets of older adults with memory decline (but not dementia) for 12 weeks found significant improvement in a measure of verbal learning. A double-blinded placebo-controlled study in which researchers gave healthy older adults 200 mg resveratrol supplements daily with 230 mg quercetin for six months found improved memory performance.2 As with curcumin, low bioavailability is a major drawback to resveratrol, which is readily metabolized and eliminated.2,13

Catechins
Also known as flavan-3-ol monomers, potent antioxidant and anti-inflammatory catechins constitute 30% to 42% of the solid weight of brewed green tea.14 They're also found in white, oolong, black, and Pu-erh tea, which all come from the leaves of the same plant.2,14 Various epidemiologic studies (which don't prove cause and effect) have associated long-term catechin intake with improved language and verbal memory and lower risk of cognitive impairment and decline. A small interventional study in healthy volunteers found an increase in brain activity on functional MRI scans after consumption of green tea.2

Tips for RDs
Fear of losing cognitive function is very real for many people. "I see some clients who are more scared of losing cognitive ability than just about any other condition," Moon says. "It helps to let them know how easy and practical a brain-healthy diet can be. There are no special foods to buy. A plan like the MIND diet is flexible; it doesn't recommend a lot of red meat or butter or hard cheeses, but there's room for them. Just eat them less often." Moon works with clients who have favorite recipes and are looking for small ways to make them a little bit more healthful. "Use olive oil in place of butter; swap out refined grains for whole grains, or do a 50:50 mix, like adding barley or farro to a pearl couscous dish," Moon says. Emphasizing richly colored fruits and vegetables and cooking with herbs and spices can boost vitamin and phytochemical intake. "Our goal is to recommend these dark colored fruits and vegetables since these are naturally rich in phytochemicals that reduce oxidative stress and protect the brain from inflammation," McDaniel says. "I also tell my clients to keep their spices visible and easily accessible and to add them to food on a regular basis. Herbs and spices make foods flavorful and add beneficial phytochemicals like curcumin to the diet. I personally add a little turmeric to my morning green smoothie."

The final word on nutrients and brain health is evolving. "It can be tempting to get caught up in research about one particular brain-boosting nutrient or food," McDaniel says. "But it's the consumption of a variety of brain-boosting foods, or dietary patterns, that makes a real difference. The good news is, we're already providing dietary advice for preserving brain health when we counsel our clients on ways to promote heart health."

Moon agrees: "There's enough research to suggest that dietary patterns like the MIND diet may be of benefit to brain health, but, regardless, we know it will be heart healthy and good for general health," Moon says. "There's not a lot of risk, and there's potential for benefit."

— Judith C. Thalheimer, RD, LDN, is a nutrition writer and speaker based outside Philadelphia, Pennsylvania.

References
1. Moore M. 4 types of foods to help boost your memory. Academy of Nutrition and Dietetics website. http://www.eatright.org/resource/health/wellness/healthy-aging/memory-boosting-foods. Published November 18, 2016.

2. Phillips C. Lifestyle modulators of neuroplasticity: how physical activity, mental engagement, and diet promote cognitive health during aging. Neural Plast. 2017;2017:3589271.

3. Morris MC, Tangney CC. Dietary fat composition and dementia risk. Neurobiol Aging. 2014;35(Suppl 2):S59-S64.

4. Johnson EJ, Vishwanathan R, Johnson MA et al. Relationship between serum and brain carotenoids, α-tocopherol, and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study. J Aging Res. 2013;2013:951786.

5. Hammond BR Jr, Miller LS, Bello MO, Lindbergh CA, Mewborn C, Renzi-Hammond LM. Effects of lutein/zeaxanthin supplementation on the cognitive function of community dwelling older adults: a randomized, double-masked, placebo-controlled trial. Front Aging Neurosci. 2017;9:254.

6. Mohn E, Vishwanathan R, Lichtenstein AH, et al. The relationship of lutein and DHA in cognitive function. FASEB J. 2013;27(Suppl 1):638.18.

7. Mohajeri MH, Troesch B, Weber P. Inadequate supply of vitamins and DHA in the elderly: implications for brain aging and Alzheimer-type dementia. Nutrition. 2015;31(2):261-275.

8. Ashpari Z, Watson K. Brain vitamins: can vitamins boost memory? Healthline website. www.healthline.com/health/dementia/vitamins-memory-loss#vitamin-e3. Updated January 25, 2017.

9. Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311(1):33-44.

10. Graff-Radford J. Can vitamin B-12 improve memory in Alzheimer's disease? Mayo Clinic website. http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/expert-answers/alzheimers/faq-20057895. Published October 14, 2016.

11. Smith D, Refsum H, Oulhaj A, de Jager CA, Jerneren F. Beneficial interactions between B vitamins and omega-3 fatty acids in the prevention of brain atrophy and of cognitive decline in early stage Alzheimer's disease. FASEB J. 2016;30(Suppl 1):407.6.

12. Higdon J. Curcumin. Oregon State University Linus Pauling Institute Micronutrient Information Center website. http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/curcumin. Updated March 2016.

13. Higdon J. Resveratrol. Oregon State University Linus Pauling Institute Micronutrient Information Center website. http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/resveratrol. Updated June 11, 2015.

14. Higdon J. Tea. Oregon State University Linus Pauling Institute Micronutrient Information Center website. http://lpi.oregonstate.edu/mic/food-beverages/tea#flavonoids. Updated January 2016.