The Best Foods for the Brain: An Update
It has been nearly a year since Medscape published Brain Food, a look at how what we eat influences our mental and neurologic health. Since then, our understanding of how diet affects the brain has grown significantly. The current slideshow, based primarily on Medscape news coverage, reviews the previous year's studies on nutrition and brain health.
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Diet for Depression
Research from the past several years suggests that consumption of monounsaturated fatty acids (found in olive oil, avocados, and nuts), polyunsaturated fatty acids (PUFAs; found in nuts, seeds, fish, and leafy green vegetables), and supplements containing eicosapentaenoic acid decreases depression risk over time.[1-3] To that end, adhering to Mediterranean dietary patterns specifically -- that is, a diet rich in fruits, vegetables, nuts, whole grains, and fish and high in unsaturated fat -- is associated with a 30% reduction in depression risk, compared with meat- and dairy-heavy diets and diets high in trans-fatty acids; intake of the latter is associated with an increased depression risk over time.[4] Conversely, low levels of PUFAs may increase the risk of developing postpartum depression, according to a 2012 literature review published in the Canadian Journal of Psychiatry.[5] Keep in mind, however, that although there is strong evidence of an association between diet and depression, most studies to date have not proven causality, supporting the need for large, randomized primary prevention trials.[6]
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Rethinking Fat
Beyond reducing depression risk, the unsaturated fatty acids common in the Mediterranean diet have other benefits for the brain. A 2012 review published in Pediatrics reported on the evidence linking PUFA deficiency to attention-deficit/hyperactivity disorder, as well as findings from trials where these fats were used successfully to address ADHD symptoms.[7] Another small study showed that increasing omega-3 fatty acid consumption enhances working memory in young adults.[8] Previous work has linked Mediterranean diets high in olive oil consumption with a lower risk for ischemic stroke,[9,10] mild cognitive impairment, and Alzheimer disease, and particularly the latter two when associated with high levels of physical activity.[11,12]
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Go With the Salmon
Oily, cold-water fish like salmon, trout, and mackerel are especially good sources of PUFAs, namely omega-3 fatty acids. According to a 2012 study,[13] 2 servings a week are associated with a modest but clinically significant reduction in stroke risk. Of note, omega-3 supplementation was not associated with a risk reduction, a finding that study author Oscar H. Franco, MD, PhD, Professor of Preventive Medicine at Erasmus Medical Center in The Netherlands, attributes to "the interplay of a wide range of nutrients abundant in fish." A 2010 study suggested that consuming a moderate amount of oily fish was protective against the risk for psychotic symptoms; however, greater intakes were associated with an increased risk.[14] This J-shaped relationship between fish or PUFA intake and mental health problems has also been suggested by other studies and is consistent with the importance of a balanced diet.[15,16] However, concurrent work from randomized controlled trials has suggested that fish oil may help prevent psychosis in high-risk individuals.[17] A multicenter, randomized double-blind study is under way to determine whether omega-3 fatty acid supplementation can help prevent the onset of psychosis and improve symptoms and outcomes in those at high risk for schizophrenia.
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Fruit to Fend Off Stroke
2012 was a good year for fruit. An analysis from the Nurses' Health Study found that high consumption of flavanones, a flavanoid subclass found in high concentrations in grapefruits and oranges, is associated with a 19% lower risk for ischemic stroke in women.[18] A Finnish study[19] published in Neurology reported that a diet high in lycopene, a potent antioxidant found in tomatoes, may cut stroke risk in men. Previous work has shown that polyphenols, namely anthocyanins, found in berries and other darkly pigmented fruits and vegetables may slow cognitive decline by inducing autophagy (a process by which cells clear proteinaceous debris linked to memory loss) and reduce cardiovascular disease risk by reducing oxidative stress and attenuating inflammatory gene expression.[20-22] Each of these studies points to the importance of a healthy diet high in plant foods and low in processed foods for a range of health outcomes, both physical and mental.
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Cut the Soda, Keep Up the Coffee
2012 saw more evidence that coffee might be the original wonder drug. A new observational study[23] to be presented at the American Academy of Neurology meeting in March shows that people who drink 4 cups of coffee a day are 10% less likely to develop depression. Those who opted for 4 or more servings a day of diet soda or fruit punch were 30% and 38% more likely, respectively, to develop depression. Past work also suggests that the world's most widely used stimulant cuts depression risk, possibly by altering serotonin and dopamine activity and through its antioxidant and anti-inflammatory properties.[24-27]
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Alcohol: Always in Moderation
The Greeks touted "nothing in excess," a refrain that still rings true: Low to moderate* alcohol consumption has been associated with numerous potential physiologic benefits with neurologic implications, including improved cholesterol profiles, beneficial effects on platelet and clotting function, and improved insulin sensitivity.[28] Last year we reported that limited alcohol use is associated with a lower risk for dementia[28,29] and that moderate alcohol -- especially antioxidant-rich red wine -- intake may protect against cerebrovascular disease.[30-32] A new study published in Circulation Research found that dealcoholized Merlot reduced blood pressure by approximately 6/3 mm Hg in a sample of 67 men at high cardiovascular risk, suggesting that the beneficial effects of wine consumption may not strictly be due to its alcohol content.[33] However, the health costs to the brain of alcohol consumption can quickly outweigh the benefits, as heavy and long-term alcohol use can lead to alcohol abuse and dependence, impair memory function, contribute to neurodegenerative disease, and hinder psychosocial functioning.
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*The US Food and Drug Administration defines "moderate alcohol consumption" as up to 1 drink per day for women and up to 2 drinks per day for men. One drink is equivalent to 12 fluid ounces of regular beer, 5 fluid ounces of 12% alcohol wine, or 1.5 fluid ounces of distilled spirits.

Chocolate -- and Still More Antioxidants
Many recent studies have added to the already robust body of evidence suggesting that dark, flavonol-rich chocolate may have cardiovascular benefits. A meta-analysis published in Cochrane Database of Systematic Reviews reported that individuals who consumed 100 g of dark chocolate every day -- a standard Hershey bar weighs 43 g -- saw an average blood pressure drop of 2.77/2.20 mm Hg compared with control participants.[34] A study out of Finland[35] published in Neurology reported that individuals who eat at least 52 g of chocolate per week have a 17% lower risk for stroke, compared with those who eat less than 12 g a week. The flavonols in dark chocolate likely contribute to the reported benefits by scavenging free radicals and improving endothelial and platelet function. But always check the label, as some processed chocolate contains trans-fats, which should be avoided.
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What Not to Eat: Cut the Carbs
Various 2012 studies further clarified how overly sweet, unhealthy foods affect the brain. An animal study[36] out of UCLA found that diets high in fructose can impair cognitive function, which is reversible with omega-3 fatty acid supplementation. Coauthor Fernando Gomez-Pinilla, PhD, told Medscape Medical News, "High fructose consumption can induce some signs of metabolic syndrome in the brain and can disrupt the signalling of the insulin receptors and reduce the action of insulin in the brain." Other work[37] published in JAMA suggests that fructose consumption modulates the neurophysiologic pathways involved in appetite regulation and encourages overeating. An October 2012 study[38] published in the Journal of Alzheimer's Disease reported that a diet high in carbohydrates and sugar raises the risk for mild cognitive impairment in the elderly, while a diet high in fat and protein may reduce this risk. Lead author Rosebud O. Roberts, MD, an epidemiologist at Mayo Clinic in Rochester, Minnesota, commented to Medscape Medical News that an "optimal balance" of carbohydrates, fat, and protein may help "maintain neuronal integrity and optimal cognitive function in the elderly."
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What Not to Eat (cont)
Mounting evidence in 2012 reinforces that high consumption of red meat increases stroke risk. The largest meta-analysis to date[39] looking at the atherogenic effects of red meat found that the risk for total stroke increased by up to 13% for each increase in a single serving of fresh, processed, and total amount of red meat consumed per day. Earlier in the year another study[40] found that processed and unprocessed red meat is associated with a higher risk for stroke, while poultry was associated with a reduced risk. A study by Sánchez-Villegas and colleagues[4] found that a diet high in fruits, vegetables, grains, and fish led to a 30% lower depression risk compared with a meaty diet. But, as we pointed out last year, meat quality might be a factor: Moderate consumption of unprocessed, free-range red meat may actually protect against depression and anxiety.[41] Mental health nutrition expert Dr. Felice Jacka, a research fellow at Deakin University in Geelong, Australia, comments in this report that despite the growing locavore movement, much of the livestock in the United States is raised on industrial feedlots, which "...increases saturated fat and decreases very important good fatty acids...pasture-raised animals have a much healthier fatty acid profile."
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