Brain Food: What to Avoid
Medscape's 2-part Brain Food slideshow series looked at how what we eat can benefit the brain. From salmon cutting stroke risk to coffee curbing depression, the data are copious. But the past couple of years have seen countless studies also looking at how certain foods and dietary patterns can impair neurologic and psychiatric function. Based primarily on Medscape Medical News coverage and expert opinion, this slideshow examines recent data on what foods we should potentially avoid in the interest of preserving our cognitive capacities, and fending off -- or at least slowing -- diseases of the brain.
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Diet and Dementia
In January, Medscape interviewed neurologist Dr. David Perlmutter -- author of New York Times bestseller Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar -- Your Brain's Silent Killers -- about the potential link between carbohydrate and gluten consumption and dementia risk. Dr. Perlmutter advocates a nearly carbohydrate-free diet high in good fats, on the basis of a growing body of research linking carbohydrate-rich diets with a higher risk for mild cognitive impairment (MCI) and dementia. The idea is based on evidence that diets high in carbs lead to increased protein glycation, a process that increases inflammation, free radical production, and oxidative stress, thereby increasing dementia risk.^[1]
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Diet and Dementia: The Data
Plenty of data back up Dr. Perlmutter's claim and dietary approach. A prospective study^[2] of over 2000 participants published in August 2013 in the New England Journal of Medicine (NEJM) reported that even small elevations in blood sugar are associated with increased dementia risk. The authors concluded, "Our results suggest that higher glucose levels may be a risk factor for dementia, even among persons without diabetes." Further, a Mayo Clinic study^[3] published in the Journal of Alzheimer's Disease in 2012 reported that in persons favoring a high-carb diet, risk for MCI was increased by 89%; in those favoring a high-fat diet, risk decreased by 44%. Work published in Lancet Neurology in 2011^[4] reported that 54% of cases of Alzheimer disease (AD) in the United States could have been prevented through lifestyle modifications, including weight loss and exercise. An effective way of lowering blood sugar according to the A TO Z trial, published in JAMA in 2007,^[5] is a lower-carb, higher-fat diet. An interventional trial published in NEJM the following year^[6] also reported weight loss and reduction of fasting blood sugar in those eating a higher-fat, lower-carb diet.
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Diet and Dementia: The Skeptics
Not so fast, say detractors of the ultra-low-carb approach to brain health. Dr. Neal D. Barnard, Adjunct Associate Professor of Medicine at the George Washington University School of Medicine in Washington, DC, commented to Medscape, "Readers might interpret Dr. Perlmutter's advice as 'go ahead and dig into the roast beef, and blame your health problems on carbohydrate.' But avoiding carbohydrates in general and grains in particular...is not the answer. First, we can take a lesson from Japan. In 1980, diabetes was rare, and the diet was very high in carbohydrate, particularly rice. Then, as westernization occurred, meat displaced rice from Japanese meals, increasing fat intake and reducing carbohydrate consumption. Between 1980 and 1990, diabetes prevalence in adults older than 40 years climbed from less than 5% to 11%-12%. Ergo, carbohydrate was clearly not the problem. Rather, rising fat intake caused insulin resistance." Dr. Barnard also points to the Chicago Health and Aging Project,^[7] a 6-year study correlating high saturated fat intake with increased risk for AD.
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More Skepticism
Dr. David L. Katz, MD, MPH, Director of the Yale-Griffin Prevention Research Center, has similar feelings. "The argument here obscures the diversity of carbohydrate (ie, everything from lentils to lollipops is a 'carb') and ignores the association between 'high-carbohydrate' diets and excellent health outcomes. The literature linking high-carbohydrate, plant-based diets, inclusive of whole grains, with risk-factor amelioration, chronic disease prevention, regression of atherosclerosis, longevity, and vitality is vast," he told Medscape. Dr. Katz cites research linking low glycemic index (GI), high-carbohydrate diets with cardiovascular risk reduction^[8] and, conversely, low-carb, high-fat diets with impaired endothelial function in those with increased cardiovascular risk,^[9] as well as data correlating plant-based diets, which include grains, with favorable metabolic profiles.^[10,11] He also points out that the longest-living, least dementia-prone populations subsist heavily on plant-based diets, which include grains.
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Fat, Carbs, and Amyloid
Saturated fat from certain sources isn't branded quite the dietary pariah it once was -- data suggest that moderate intake of high-quality, free-range red meat may protect against depression and anxiety -- but too much, when combined with a high-carb diet, may still be detrimental to the brain. A small 2013 study^[12] found that diets high in saturated fat and with high GIs increase levels of unbound amyloid-beta in the cerebrospinal fluid (CSF). The normal clearing of amyloid from the brain involves it binding to apolipoprotein E; if unbound, amyloid clusters into plaques, a pathologic hallmark of AD. The previously mentioned Chicago Health and Aging Project^[7] found that black persons (only) consuming the most saturated fat (~25 g/day) were 2-3 times more likely to develop AD than those who consumed one half that amount. However, in this study, the intake of carbohydrates (either low or high GI) was not taken into account; moreover, those in the lowest categories of saturated fat intake also had higher intake of dietary vitamin C, suggesting that they had overall healthier diets. Although antioxidant intake was statistically adjusted for in this study, without an analysis of overall dietary patterns or quality, it is difficult to attribute risk reduction directly to one particular component of diet.
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New Guidelines and Conflicting Data
In July 2013, the Physicians Committee for Responsible Medicine (PCRM) released dietary guidelines for the prevention of AD that take a much different stance from the low-carb, high-fat approach. Dr. Barnard served as lead author on the report, which includes recommendations to minimize saturated fats and to include whole grains among dietary staples. Among the research supporting the recommendations are the Chicago Health and Aging Project^[7] and study of Kaiser Permanente^[13] patients showing that participants with total cholesterol levels above 250 mg/dL in middle age had a 50% higher risk for AD 3 decades later, compared with those with levels below 200 mg/dL. However, another recent study from The Netherlands found that avoiding saturated fat does not protect against AD.^[14]

Diet and Depression
A 2012 cohort study^[15] of nearly 9000 Spanish adults that was published in Public Health Nutrition found that participants who frequently consumed fast food were 40% more likely to develop depression than those avoiding burgers, pizza, and the like. This comes on the heels of work^[16] by the same group from 2011 showing a positive dose/response relationship between trans fat intake and the risk for depression. Olive oil, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were linked in the same study with a protective effect and lower depression risk. Similarly, Felice N. Jacka, PhD, and team reported^[17,18] that dietary patterns characterized by higher intakes of processed or fried foods, refined grains, and sugary products (a "Western," or unhealthy, dietary pattern) were associated with increased depression and anxiety in both Australian and Norwegian adults. Similarly, an unhealthy dietary pattern was linked to an increased risk for self-reported depression over time in public servants from the United Kingdom.^[19]
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Disclosure: Dr. Jacka served as a reviewer for this slideshow.

Alcohol Up In the Air
Data on the effects of alcohol on the brain are conflicting and appear to be heavily dose-dependent. Mild to moderate consumption has been associated with lower risk for dementia and, particularly in the case of red wine, protection against cardiovascular disease.^[20-24] Recent work also suggests that limited consumption is tied to improved cholesterol profiles, platelet and clotting function, and improved insulin sensitivity and may even protect against multiple sclerosis.^[25] However, the evidence takes a concerning turn with heavier consumption, potentially leading to abuse and dependence, impaired memory function, impaired psychosocial and occupational functioning, and neurodegenerative disease. A study published in Neurology in January 2014 reported that middle-aged men who drink over 2.5 drinks daily are more likely to undergo faster decline in all cognitive areas -- particularly memory -- during a period of 10 years. In short, enjoy Merlot in moderation.^[26]
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The Pediatric Brain
Recent studies have looked at the possible effects of diet on the developing brain. Australian data^[27] from 2011, published in PLoS One, linked unhealthy diets with poorer mental health in more than 3000 adolescents aged 11-18 years. Investigators found that those whose diets were higher in snack and processed foods scored significantly worse on the Pediatric Quality of Life Inventory (PedsQL), whereas those whose diet quality worsened over time also experienced a deterioration in their mental health over 2 years of follow-up. More recently, a large Norwegian cohort study^[28] from 2013 found that "dietary patterns during pregnancy and in the first 5 years of life have important relationships to children's mental health," as reported by Medscape Medical News. Children who ate more junk food -- for example, processed sweets, soda, and pizza -- in the first years of life demonstrated more internalizing behaviors, such as worry, sadness, crying, and anxiety, and also more externalizing behaviors, such as aggression, tantrums, and hyperactivity, over the ages of 18 months to 5 years. Of note, moms who ate more of these sorts of food while pregnant had children with higher levels of externalizing behaviors, independent of the children's diets.
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Brain Food: What Should We Eat?
In short, the jury's still out. As previously reported on Medscape, work from the past several years suggests that diets high in MUFAs (found in olive oil, avocados, and nuts), PUFAs (found in nuts, seeds, fish, and leafy green vegetables), and supplements containing eicosapentaenoic acid may decrease depression risk over time.^[15,16,29] Relatedly, adhering to Mediterranean dietary patterns specifically -- a term that is open to interpretation but has generally come to refer to diets 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 those high in trans fatty acids; intake of the latter is associated with an increased depression risk.^[30] However, as discussed previously, data are conflicting as to the impact of both carbohydrates and fats on the brain; clearly more study is needed.
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More Conclusions
A reductionist focus on individual nutritional factors, such as carbohydrates or saturated fats, ignores the fact that each component of diet interacts with other components in highly complex ways. As such, it is far more important to focus on the whole diet when aiming to improve health outcomes, and in this sense the Mediterranean diet has the strongest evidence base. A recent systematic review concluded that adherence to healthy diets reduces the risk for both depression and cognitive decline,^[31] and the large PREDIMED randomized trial showed that Mediterranean diets reduce the risk for heart disease,^[32] improve cognition, and may also prevent depression.^[33,34] As such, diets high in fruits, vegetables, fish, plant oils, nuts and whole grains, with lower intakes of sugar, processed meat, and animal fats, are likely to be the best bet in supporting the health of our brain as well as the rest of our body. Such diets are concordant with national dietary guidelines from around the world. The key message is that physical health may be just as important to mental health as mental health is to physical health. Physicians should ensure that they discuss the importance of diet with all of their patients, including those with mental health problems.
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