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CHAPTER FIVE

ADHD: Gluten, Milk Caseins, and Polyphenols

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ADHD AND YOUR GUT

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When you have ADHD, the connections between different brain regions are disrupted, specifically between the prefrontal cortex, the “thinking” brain, and the striatum, the part of the brain that deals with reward behaviors. Additionally, your brain chemistry is affected, particularly your levels of dopamine, the brain’s “reward” chemical, and noradrenaline, a fight-or-flight hormone.6

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6. Curatolo P, D’Agati E, Moavero R. The neurobiological basis of ADHD. Italian Journal of Pediatrics. 2010;36(1):79. doi:10.1186/1824-7288-36-79.

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what role does your gut play? Larger molecules such as dopamine and noradrenaline cannot cross the blood-brain barrier, which means that they are confined solely to your brain. But they are made of precursor molecules—building blocks—that can. And where are these precursor molecules made? You guessed it: the gut.

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Gut bacteria play an important role in ADHD, synthesizing many of these chemical precursors.7 Different bacterial species in the gut produce different chemicals, which means that if gut bacteria change, the brain’s chemical stability can be upset.8 And as we’ve seen with other conditions, a reduction in the diversity of gut bacteria can be particularly problematic.9

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7. Lyte M. Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. Miller V, ed. PLoS Pathogens. 2013;9(11):e1003726. doi:10.1371/journal.ppat.1003726.

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8. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. Journal of Psychiatric Research. 2008;43(2):164–74. doi:10.1016/j.jpsychires.2008.03.009; Clayton TA. Metabolic differences underlying two distinct rat urinary phenotypes, a suggested role for gut microbial metabolism of phenylalanine and a possible connection to autism. FEBS Letters. 2012;586(7):956–61. doi:10.1016/j.febslet.2012.01.049; Gertsman I, Gangoiti JA, Nyhan WL, Barshop BA. Perturbations of tyrosine metabolism promote the indolepyruvate pathway via tryptophan in host and microbiome. Molecular Genetics and Metabolism. 2015;114(3):431–37. doi:10.1016/j.ymgme.2015.01.005.

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9. Sandgren AM, Brummer RJM. ADHD-originating in the gut? The emergence of a new explanatory model. Medical Hypotheses. 2018;120:135–45. doi:10.1016/j.mehy.2018.08.022.

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In 2017, Esther Aarts and her colleagues examined the differences in the microbiome between patients with ADHD and healthy individuals.10 Compared to controls, people with ADHD had more bacteria that made phenylalanine, a building block necessary for dopamine and noradrenaline synthesis.

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10. Aarts E, Ederveen THA, Naaijen J, et al. Gut microbiome in ADHD and its relation to neural reward anticipation. Hashimoto K, ed. PLoS One. 2017;12(9):e0183509. doi:10.1371/journal.pone.0183509.

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The investigators then looked at how the brains of each group responded to reward. Decreased anticipation of brain reward is a hallmark of ADHD—in other words, studies show that people with ADHD aren’t motivated as strongly by incentives to behave in a certain way.11 Sure enough, the researchers found that the ADHD subjects showed less brain activation in response to being rewarded. Furthermore, the less their brains responded to the reward, the more phenylalanine-producing bacteria were present in their guts. The researchers concluded that ADHD subjects had to make more bacteria that produce phenylalanine to compensate for how their brains responded.

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11. Volkow ND, Wang G-J, Newcorn JH, et al. Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway. Molecular Psychiatry. 2010;16(11):1147–54. doi:10.1038/mp.2010.97.

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FOODS THAT WORSEN ADHD

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a well-established link between ADHD and gluten intolerance or celiac disease. In 2006, Helmut Niederhofer and Klaus Pittschieler assessed a sample of people across a broad age range to test the association between ADHD and celiac disease.13 The participants’ ADHD symptoms were measured before they started a gluten-free diet and six months after. The study found that people who had celiac disease were more likely to have ADHD, and a gluten-free diet improved their symptoms after the initial six-month period.

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13. Niederhofer H, Pittschieler K. A preliminary investigation of ADHD symptoms in persons with celiac disease. Journal of Attention Disorders. 2006;10(2):200–204. doi:10.1177/1087054706292109.

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you don’t have to have celiac disease to be sensitive to gluten. This condition is called non-celiac gluten sensitivity.14 While the association between non-celiac gluten sensitivity and ADHD is by no means conclusive, various studies point to a connection between the two. In some instances, as we saw in chapter 3 with my “silent celiac” patient Rex, gluten sensitivity may cause neurologic and psychiatric symptoms without any corresponding digestive symptoms.15 People typically associate gluten sensitivity with digestive issues, so in the absence of upset stomach or bowel symptoms, gluten isn’t on the radar as a factor that can worsen ADHD.

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14. Cruchet S, Lucero Y, Cornejo V. Truths, myths and needs of special diets: attention-deficit/hyperactivity disorder, autism, non-celiac gluten sensitivity, and vegetarianism. Annals of Nutrition and Metabolism. 2016;68(1):43–50. doi:10.1159/000445393.

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15. Jackson JR, Eaton WW, Cascella NG, Fasano A, Kelly DL. Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity. Psychiatric Quarterly. 2011;83(1):91–102. doi:10.1007/s11126-011-9186-y.

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The exact reason that gluten sensitivity and brain dysfunction are connected is not fully understood. In 2005, Päivi A. Pynnönen and her colleagues assessed adolescents with celiac disease and behavioral problems.16 They found that adolescent celiac disease patients had significantly lower tryptophan concentrations in their blood.

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16. Pynnönen PA, Isometsä ET, Verkasalo MA, et al. Gluten-free diet may alleviate depressive and behavioural symptoms in adolescents with coeliac disease: a prospective follow-up case-series study. BMC Psychiatry. 2005;5(1). doi:10.1186/1471-244x-5-14.

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Three months after patients started a gluten-free diet, the researchers found a significant decrease in patients’ psychiatric symptoms compared to their baseline condition, coinciding with significantly decreased celiac disease activity and prolactin levels and with a significant increase in L-tyrosine, L-tryptophan, and other amino acids known to be precursors of brain chemicals such as serotonin. The authors concluded that it was possible that behavioral problems, such as those that occur with ADHD, may in part be due to certain important precursor amino acids not being available until people stopped eating gluten. In certain individuals, gluten-free diets can help the body increase levels of the precursors to make serotonin, which is one neurotransmitter involved in ADHD.

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Dairy

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Eating a lot of dairy means you eat a lot of casein, which may worsen ADHD.17 Casein is the main protein found in dairy products such as milk, cheese, yogurt, and ice cream, but it can be a factor even in foods that are thought of as dairy substitutes, like nondairy creamer and margarine.

Not all casein is the same. The main form is called beta-casein, of which there are two major types, A1 and A2. Most regular milk contains both types, but research suggests that A1 proteins may be harmful to the gut in ways that A2 proteins are not.

In 2016, a team led by Sun Jianqin studied forty-five participants who consumed milk containing both A1 and A2 milk proteins, and then milk containing only A2 protein.18 The researchers found that when subjects drank milk containing A1 protein, they had more gastrointestinal inflammation, their thinking was slower, and they made more errors on an information-processing test. It was as if the A1 protein muddied their thinking, something that ADHD patients can ill afford. The study even suggested that lactose intolerance may be caused by sensitivity to A1 caseins rather than lactose itself.

Although more research is under way about whether A1 milk causes any adverse effects except occasional digestive problems, it’s clear that sufferers of ADHD should be cautious about the kind of casein they consume.19

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17. Ly V, Bottelier M, Hoekstra PJ, Arias Vasquez A, Buitelaar JK, Rommelse NN. Elimination diets’ efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. European Child and Adolescent Psychiatry. 2017;26(9):1067–79. doi:10.1007/s00787-017-0959-1.

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18. Jianqin S, Leiming X, Lu X, Yelland GW, Ni J, Clarke AJ. Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows’ milk. Nutrition Journal. 2015;15(1). doi:10.1186/s12937-016-0147-z.

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19. Küllenberg de Gaudry D, Lohner S, Schmucker C, et al. Milk A1 β-casein and health-related outcomes in humans: a systematic review. Nutrition Reviews. 2019;77(5):278–306. doi:10.1093/nutrit/nuy063.

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Luckily there is milk available that only has A2 proteins. Milk from breeds of cows that originated in Northern Europe is generally high in A1 protein. These breeds include Holstein, Friesian, Ayrshire, and British shorthorn. Milk that is high in A2 protein is mainly found in breeds that originated in the Channel Islands and southern France. These include Guernsey, Jersey, Charolais, and Limousin cows.20 Of course, it’s not often practical to choose what kind of cows your milk comes from! However, there are now A2-only milks available in many grocery stores and online.

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20. Truswell AS. The A2 milk case: a critical review. European Journal of Clinical Nutrition. 2005;59(5):623–631. doi:10.1038/sj.ejcn.1602104; Farrell HM Jr, Jimenez-Flores R, Bleck GT, et al. Nomenclature of the proteins of cows’ milk—sixth revision. Journal of Dairy Science. 2004;87(6):1641–74. doi:10.3168/jds.s0022-0302(04)73319-6.

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While it’s great to have A2 protein milk available, since much of the dairy we consume is in the form of cheese, yogurt, butter, and prepared foods, cutting out A1 caseins still requires significant dietary changes. It’s worth noting that sheep’s and goats’ milk is generally A2 milk, which makes cheese and yogurt choices a bit easier. You can also try nut milks and milk nut yogurts as a way to avoid casein.

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Sugar

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sugar can have an effect on ADHD through several pathways. For instance, because it can increase adrenaline, a hormone that increases heartbeat and blood sugar levels, sugar may cause more hyperactivity.21 And because it reduces dopamine sensitivity in the brain, sugar can amplify impulsive reward-seeking behavior that is common in ADHD.22

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21. Dykman KD, Dykman RA. Effect of nutritional supplements on attentional-deficit hyperactivity disorder. Integrative Physiological and Behavioral Science. 1998;33(1):49–60.

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22. Johnson RJ, Gold MS, Johnson DR, et al. Attention-deficit/hyperactivity disorder: is it time to reappraise the role of sugar consumption? Postgraduate Medicine. 2011;123(5):39–49. doi:10.3810/pgm.2011.09.2458.

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In 2019, Bianca Del-Ponte and her colleagues investigated whether high sugar intake was associated with ADHD in a study of children between the ages of six and eleven years old.23 Through interviews and diet monitoring, the researchers were able to calculate the actual sucrose consumption of all the children in the study. Trained interviewers collected data on whether children met the criteria for ADHD or not.

Although they found that high sucrose consumption was more common in six-year-old boys with ADHD compared to those without ADHD, this effect was not seen in children of other ages in either gender. Changing sucrose consumption between six and eleven years of age also did not affect the incidence of ADHD in boys or girls. Overall, the researchers concluded that sugar consumption does not lead to ADHD. If there is any correlation, children with ADHD may simply consume more sugar.

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23. Del-Ponte B, Anselmi L, Assunção MCF, et al. Sugar consumption and attention-deficit/hyperactivity disorder (ADHD): a birth cohort study. Journal of Affective Disorders. 2019;243:290–96. doi:10.1016/j.jad.2018.09.051.

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Food Colorings, Additives, and the Few Foods Diet

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The earliest research on the effect of food on ADHD can be traced back forty years, when pediatric allergist Benjamin Feingold hypothesized that both artificial food additives (colorings and flavors) and foods rich in salicylates might make children more inattentive and restless.

Salicylates are chemicals found naturally in some fruits, vegetables, coffee, tea, nuts, spices, and honey. They are synthesized for use in medications like aspirin, Pepto-Bismol, and other products.

In 1976 Feingold formulated a diet that eliminated food additives and salicylates, which would come to be known as the Feingold diet.25 Some people refer to it as the Kaiser Permanente diet. It was popular in its early days, though the effects were poorly understood. The studies by Dr. Feingold were followed by other studies investigating the effects of eliminating artificial food coloring and eventually led to a diet eliminating many foods and additives, called the few foods diet. This diet is essentially an elimination diet, a category of diets pioneered in 1926 by food allergy specialist Albert Rowe and still in use today.26 In this approach, you remove one potentially offending food at a time and carefully record any changes in symptoms, before adding foods back in one at a time.

In 1983, a meta-analysis found that the effect of the Feingold diet on ADHD was actually quite weak, casting doubt on the efficacy of elimination diets in improving ADHD in general.27 However, in 2004, another meta-analysis of only the higher-quality studies demonstrated that eliminating food colorings seemed to make a difference in parents’ observations of children with ADHD, but not in teachers’ or other caretakers’ observations.28

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24. Yu C-J, Du J-C, Chiou H-C, et al. Sugar-sweetened beverage consumption is adversely associated with childhood attention deficit/hyperactivity disorder. International Journal of Environmental Research and Public Health. 2016;13(7):678. doi:10.3390/ijerph13070678.

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25. Feingold BF. Hyperkinesis and learning disabilities linked to artificial food flavors and colors. American Journal of Nursing. 1975;75(5):797–803.

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26. Spitler DK. Elimination diets and patient’s allergies. A handbook of allergy. Bulletin of the Medical Library Association. 1944;32(4):534.

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27. Kavale KA, Forness SR. Hyperactivity and diet treatment. Journal of Learning Disabilities. 1983;16(6):324–30. doi:10.1177/002221948301600604.

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28. Schab DW, Trinh NH. Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials. Journal of Developmental and Behavioral Pediatrics. 2004;25(6):423–34.

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A 2012 meta-analysis by Joel Nigg and his colleagues and a 2017 meta-analysis by Lidy Pelsser demonstrated that a restriction diet that eliminated food-coloring additives benefited some children with ADHD, determining that between 10 and 30 percent of people with ADHD would likely respond.29

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29. Nigg JT, Lewis K, Edinger T, Falk M. Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives. Journal of the American Academy of Child and Adolescent Psychiatry. 2012;51(1):86–97.e8. doi:10.1016/j.jaac.2011.10.015; Nigg JT, Holton K. Restriction and elimination diets in ADHD treatment. Child and Adolescent Psychiatric Clinics of North America. 2014;23(4):937–53. doi:10.1016/j.chc.2014.05.010; Pelsser LM, Frankena K, Toorman J, Rodrigues Pereira R. Diet and ADHD, reviewing the evidence: a systematic review of meta-analyses of double-blind placebo-controlled trials evaluating the efficacy of diet interventions on the behavior of children with ADHD. PLoS One. 2017 Jan 25;12(1):e0169277. doi:10.1371/journal.pone.0169277.

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FOODS FOR FOCUS

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several studies have shown that ADHD responds well to the Mediterranean eating pattern, which we discussed in chapter 2. In 2017, Alejandra Ríos-Hernández and her colleagues studied 120 children and adolescents and found that those who did not stick to the Mediterranean diet were more likely to have ADHD.31 Other studies have confirmed that low adherence to the Mediterranean diet is associated with ADHD.32

Dude why the hell would people with adhd avoid a diet that elevated their symptoms?Maybe it’s the fact they respond to other types of food poorly that is actually a cause for symptoms.

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30. Ghanizadeh A, Haddad B. The effect of dietary education on ADHD, a randomized controlled clinical trial. Annals of General Psychiatry. 2015;14:12.

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31. Ríos-Hernández A, Alda JA, Farran-Codina A, Ferreira-García E, Izquierdo-Pulido M. The Mediterranean diet and ADHD in children and adolescents. Pediatrics. 2017;139(2):e20162027. doi:10.1542/peds.2016–2027.

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32. San Mauro Martín I, Blumenfeld Olivares JA, Garicano Vilar E, et al. Nutritional and environmental factors in attention-deficit hyperactivity disorder (ADHD): a cross-sectional study. Nutritional Neuroscience. 2017;21(9):641–47. doi:10.1080/1028415x.2017.1331952.

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Breakfast

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In 2017, David O. Kennedy and his colleagues explored what morning nutrients could be helpful for ADHD sufferers.34 They compared the cognition of ninety-five people after they ate a noncommercial nutrient-enriched breakfast bar made for this study (containing alpha-linolenic acid, L-tyrosine, L-theanine, vitamins, minerals, and 21.5 mg of caffeine) versus a control bar for fifty-six days. Then they examined how cognitive function differed before eating the bars and at 40 and 160 minutes after eating the bars. They found that in all tests, people who ate the nutrient-enriched bars were more alert and attentive, and they could process information more rapidly.

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34. Kennedy DO, Wightman EL, Forster J, Khan J, Haskell-Ramsay CF, Jackson PA. Cognitive and mood effects of a nutrient enriched breakfast bar in healthy adults: a randomised, double-blind, placebo-controlled, parallel groups study. Nutrients. 2017;9(12):1332. doi:10.3390/nu9121332.

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Caffeine

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One notable factor in the breakfast bar study discussed in the previous section was the caffeine. In animals, caffeine has been shown to have beneficial effects on attention and memory, and a 2011 study demonstrated that tea might be an effective treatment for adult ADHD.35 Presumably, the caffeine in tea increases people’s motivation, alertness, vigilance, efficiency, concentration, and cognitive performance. On the other hand, caffeine may cause overexcitability too, so it’s important not to overdo it.36

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35. Bidwell LC, McClernon FJ, Kollins SH. Cognitive enhancers for the treatment of ADHD. Pharmacology Biochemistry and Behavior. 2011;99(2):262–74. doi:10.1016/j.pbb.2011.05.002; Liu K, Liang X, Kuang W. Tea consumption may be an effective active treatment for adult attention deficit hyperactivity disorder (ADHD). Medical Hypotheses. 2011;76(4):461–63. doi:10.1016/j.mehy.2010.08.049.

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36. Ioannidis K, Chamberlain SR, Müller U. Ostracising caffeine from the pharmacological arsenal for attention-deficit hyperactivity disorder—was this a correct decision? A literature review. Journal of Psychopharmacology. 2014;28(9):830–36. doi:10.1177/0269881114541014.

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the amount of caffeine that you consume matters. Again, our guideline is no more than 400 mg of caffeine per day for adults.

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Polyphenols

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In 2018, Annelies Verlaet and her colleagues found that natural antioxidants like dietary polyphenols could be useful in combating ADHD, helping to alleviate oxidative stress on the brain.37

Studies have shown that people with ADHD are at a greater risk of oxidative stress in brain tissue.38 This can lead to damaged brain cells and altered neurotransmitter levels (like dopamine) and electrical-signal transmission, which can make ADHD worse.

Or cause it 🤷‍♂️

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37. Verlaet A, Maasakkers C, Hermans N, Savelkoul H. Rationale for dietary antioxidant treatment of ADHD. Nutrients. 2018;10(4):405. doi:10.3390/nu10040405.

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38. Joseph N, Zhang-James Y, Perl A, Faraone SV. Oxidative stress and ADHD. Journal of Attention Disorders. 2013;19(11):915–24. doi:10.1177/1087054713510354.

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Since ADHD sufferers appear to lack some of the natural ability to fight off oxidative stress, it is particularly important for them to get as many antioxidants as possible through food in order to alleviate their symptoms and prevent brain cell damage.

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One crucial type of antioxidant is polyphenols. Polyphenols are chemical weight lifters for the body’s immune response. They act as low-dose toxins that train the body to mount an immune response in a process called hormesis. Polyphenols can also exert other biological effects that are helpful to the brain; for example, they influence the survival and regeneration of neurons.

The richest sources of polyphenols are berries, cherries, eggplant, onions, kale, coffee, and green tea.

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Dietary Micronutrients

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Some animal and human studies have indicated that when there is a deficiency of zinc, hyperactivity may occur.39 Indeed, zinc deficiencies are associated with ADHD in children, in part because its absence reduces the activity of reward pathways that rely on dopamine.40

Other studies have shown that children with ADHD have lower levels of iron and magnesium than controls, both of which are involved in dopamine synthesis.41

In 2017, Jin Young Kim and her colleagues studied 318 healthy children to see if their diets impacted their cognition. They used the Symbol Digit Modalities Test (SDMT), a test of speed of information processing, to see which dietary elements were beneficial.42 They found that the consumption of vitamin C, potassium, vitamin B1, and nuts all increased performance on the SDMT. In addition, the more mushrooms people ate, the better they were able to reason, while noodles and fast food decreased SDMT scores.

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39. Golub MS, Takeuchi PT, Keen CL, Hendrick AG, Gershwin ME. Activity and attention in zinc-deprived adolescent monkeys. American Journal of Clinical Nutrition. 1996;64(6):908–15. doi:10.1093/ajcn/64.6.908.

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40. Gao Q, Liu L, Qian Q, Wang Y. Advances in molecular genetic studies of attention deficit hyperactivity disorder in China. Shanghai Archives of Psychiatry. 2014;26(4):194–206; Lepping P, Huber M. Role of zinc in the pathogenesis of attention-deficit hyperactivity disorder: implications for research and treatment. CNS Drugs. 2010;24(9):721–28.

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41. Cortese S, Angriman M, Lecendreux M, Konofal E. Iron and attention deficit/hyperactivity disorder: what is the empirical evidence so far? A systematic review of the literature. Expert Review of Neurotherapeutics. 2012;12(10):1227–40; Curtis LT, Patel K. Nutritional and environmental approaches to preventing and treating autism and attention deficit hyperactivity disorder (ADHD): a review. Journal of Alternative and Complementary Medicine. 2008;14(1):79–85.

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42. Kim JY, Kang HL, Kim DK, Kang SW, Park YK. Eating habits and food additive intakes are associated with emotional states based on EEG and HRV in healthy Korean children and adolescents. Journal of the American College of Nutrition. 2017;36(5):335–41.

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CHAPTER TWO

Depression: Probiotics, Omega-3s, and the Mediterranean Eating Pattern

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DEPRESSION AND YOUR GUT

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a cross-sectional research study of depressed college students found that 30.3 percent ate fried foods, 49 percent drank sweetened drinks, and 51.8 percent ate sugary food two to seven times per week.1

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1. Lazarevich I, Irigoyen Camacho ME, Velázquez-Alva MC, Flores NL, Nájera Medina O, Zepeda Zepeda MA. Depression and food consumption in Mexican college students. Nutrición Hospitalaria. 2018;35(3):620–26.

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food changes the types of bacteria present in your gut microbiome. Your gut bacteria may become less diverse as a result of your diet, which may cause the bad bacteria to outgrow the good bacteria, triggering a cascade of negative health effects. Food can also influence the chemical messages these bacteria send from your gut up to your brain along the vagus nerve—signals that can make you feel either depressed and drained or uplifted and energized.

Animal research first led scientists to theorize that people who are depressed have different populations of gut bacteria than those who are not depressed. For instance, in mice, when the brain’s main center for smell is surgically removed, the mice exhibit depression-like behavior. These changes were accompanied by alterations in gut bacteria. In other words, inducing depression in mice changes their gut activity and bacteria.

Studies in humans appear to confirm this hypothesis. In 2019, psychiatrist Stephanie Cheung and her colleagues summarized findings from six studies3 that looked at gut health in patients with depression. They reported that patients with major depressive disorder had at least fifty types of bacterial species in their gut microbiome that were different from those of control subjects without major depressive disorder. Recent research suggests that bacterial species associated with higher quality-of-life indicators are depleted in depressed subjects, while bacteria that cause inflammation are often found in higher numbers in people suffering from depression. This tells us that inflammation and depression are closely linked.

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2. Rao TS, Asha MR, Ramesh BN, Rao KS. Understanding nutrition, depression and mental illnesses. Indian Journal of Psychiatry. 2008;50(2):77–82.

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3. Cheung SG, Goldenthal AR, Uhlemann A-C, Mann JJ, Miller JM, Sublette ME. Systematic review of gut microbiota and major depression. Frontiers in Psychiatry. 2019;10:34. doi:10.3389/fpsyt.2019.00034.

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Fighting Depression with Probiotics and Prebiotics

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Probiotics are live bacteria that convey health benefits when eaten. Probiotic-rich foods contain beneficial bacteria that help your body and brain. An animal study in 2017 from the University of Virginia School of Medicine indicated that Lactobacillus, a single gut bacterium commonly found in live cultures in yogurt, can reverse depression in rats. This bacterium is often an ingredient in human probiotic supplement formulations. More recently, similar findings have been established in humans as well.

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Prebiotics are essentially food for helpful bacteria, certain types of fiber that we cannot digest but the good bacteria in our guts can. For probiotics to be effective, it is helpful for them to have prebiotic foods available in the gut to digest. Probiotics break down prebiotics to form short-chain fatty acids that help reduce gut inflammation, block the growth of cancerous cells, and help the growth of healthy cells.

In 2010, Michael Messaoudi and his colleagues studied fifty-five healthy men and women who were randomly assigned to receive either a daily probiotic formula or a placebo for thirty days.4 Before and after treatment, the research subjects filled out questionnaires about their mood. They also provided urine samples so that their levels of cortisol, the body’s main stress hormone, could be checked.

Compared to the placebo group, those in the probiotic group reported less depression, and urinary levels of cortisol were lower, indicating that their brains were less depressed and less stressed.

Why was this the case? Certain species of gut bacteria have the ability to boost levels of brain chemicals such as gamma-aminobutyric acid, which may speed relief from depression and other mental health conditions.5

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4. Messaoudi M, Lalonde R, Violle N, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition. 2010;105(5):755–64. doi:10.1017/s0007114510004319.

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5. Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E, Wakefield S. Gut microbiota’s effect on mental health: the gut-brain axis. Clinical Practice. 2017;7(4):987.

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Probiotics are available in supplements, but it’s preferable to increase your levels of friendly bacteria through dietary sources. Yogurt with active cultures is one of the best sources of probiotics; just avoid fruited yogurts high in added sugars. Other probiotic-rich foods include tempeh, miso, and natto (fermented soybean products); sauerkraut; kefir (soured yogurt); kimchi (Korean pickle); kombucha (a fermented tea drink); buttermilk; and select cheeses such as cheddar, mozzarella, and Gouda. Examples of prebiotic-rich foods include beans and other legumes, oats, bananas, berries, garlic, onions, dandelion greens, asparagus, Jerusalem artichokes, and leeks.

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FOODS THAT DULL YOUR MOOD

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As evidenced by a 2019 study by Heather M. Francis and her colleagues, there is strong evidence that poor diet is connected to depression.6

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6. Francis HM, Stevenson RJ, Chambers JR, Gupta D, Newey B, Lim CK. A brief diet intervention can reduce symptoms of depression in young adults—a randomised controlled trial. PLoS One. 2019;14(10):e0222768.

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Sugar

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While scientific literature backs the long-held notion that feeling down in the dumps can lead you to overindulge in sugary treats, it also suggests the opposite to be true: the more sugar you eat, the more likely you are to be depressed. In 2002, Arthur Westover and Lauren Marangell found a profound correlation between people who ate sugar and those with depression.7 Statistically speaking, a perfect correlation is 1. Researchers almost never hit this mark, because there are always exceptions. But in their study, these researchers reported the correlation between eating sugar and having depression at 0.95—that’s pretty close to 1. And this was true across six countries!

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7. Westover AN, Marangell LB. A cross-national relationship between sugar consumption and major depression? Depression and Anxiety. 2002;16:118–20. doi:10.1002/da.10054.

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In 2019, a meta-analysis of ten previously published observational studies including 37,131 people with depression concluded that consuming sugar-sweetened beverages put people at a higher risk for depression. If they drank just over a 12-ounce can of soda a day (about 45 grams of sugar) they increased their risk by 5 percent. But if they drank two and a half cans of soda a day (about 98 grams of sugar), their risk jumped to 25 percent.8 In other words, more sugar consumed also meant a greater risk of depression. Pay attention to the sugar content of what you drink.

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8. Hu D, Cheng L, Jiang W. Sugar-sweetened beverages consumption and the risk of depression: a meta-analysis of observational studies. Journal of Affective Disorders. 2019;245:348–55. doi:10.1016/j.jad.2018.11.015.

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The brain relies on glucose, a type of sugar, from the food we eat in order to survive and to function. Over a twenty-four-hour period, the brain needs only 62 grams of glucose to do its job, an incredible display of energy efficiency considering the brain has at least 100 billion cells. You can easily meet this need through healthy, whole foods. Consuming unhealthy processed foods like baked goods and soda, which are loaded with refined and added sugars, often in the form of high-fructose corn syrup, floods the brain with too much glucose. This “sugar flood” can lead to inflammation in the brain and may ultimately result in depression.

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Research also shows that higher blood-glucose levels are linked to lower levels of brain-derived neurotrophic factor (BDNF) in rats. BDNF is a protein found in the brain, gut, and other tissues that is critical to helping the brain grow and develop, as well as helping the brain adapt to stress.9 So you won’t be surprised to hear that studies have found low levels of BDNF in women with depression.10 BDNF may also improve the effect of antidepressant drugs, another indicator that it plays an important role in preventing depression.11

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9. Marosi K, Mattson MP. BDNF mediates adaptive brain and body responses to energetic challenges. Trends in Endocrinology and Metabolism. 2014;25(2):89–98.

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10. Aydemir C, Yalcin ES, Aksaray S, et al. Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2006;30(7):1256–60. doi:10.1016/j.pnpbp.2006.03.025.

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11. Arumugam V, John V, Augustine N, et al. The impact of antidepressant treatment on brain-derived neurotrophic factor level: an evidence-based approach through systematic review and meta-analysis. Indian Journal of Pharmacology. 2017;49(3):236. doi:10.4103/ijp.ijp_700_16.

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High-Glycemic-Load Carbohydrates

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Even if high-carbohydrate foods—for example, bread, pasta, and anything else made from refined flour—don’t taste sweet, your body still processes them in much the same way it does sugar. That means they can also raise your risk for depression. Don’t panic, I’m not going to suggest eliminating carbs from your diet completely! But the quality of the carbs you eat matters.

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In 2018, researchers sought to evaluate which particular carbohydrates, if any, had an association with depression.12 They administered a questionnaire called the carbohydrate-quality index to 15,546 participants. “Better-quality” carbohydrates were defined as whole grains, foods high in fiber, and those ranked low on the glycemic index (GI). The GI is a measure of how quickly foods convert to glucose when broken down during digestion; the faster a food turns into glucose in the body, the higher its GI ranking.

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Of the participants in this study, 769 people were found to be depressed. The researchers discovered that people who had the highest score on the carbohydrate-quality index, meaning they were eating better-quality carbs, were also 30 percent less likely to develop depression than those who were eating high-GI carbs. In other words, a high-GI diet appears to be a risk factor for depression.13 High-GI carbs include potatoes, white bread, and white rice. Honey, orange juice, and whole-meal breads are medium-GI foods. Low-GI foods include green vegetables, most fruits, raw carrots, kidney beans, chickpeas, and lentils.

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12. Sánchez-Villegas A, Zazpe I, Santiago S, Perez-Cornago A, Martinez-Gonzalez MA, Lahortiga-Ramos F. Added sugars and sugar-sweetened beverage consumption, dietary carbohydrate index and depression risk in the Seguimiento Universidad de Navarra (SUN) Project. British Journal of Nutrition. 2017;119(2):211–21. doi:10.1017/s0007114517003361.

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13. Gangwisch JE, Hale L, Garcia L, et al. High glycemic index diet as a risk factor for depression: analyses from the Women’s Health Initiative. American Journal of Clinical Nutrition. 2015;102(2):454–63. doi:10.3945/ajcn.114.103846; Salari-Moghaddam A, Saneei P, Larijani B, Esmaillzadeh A. Glycemic index, glycemic load, and depression: a systematic review and meta-analysis. European Journal of Clinical Nutrition. 2018;73(3):356–65. doi:10.1038/s41430-018-0258-z.

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In order to minimize your chance for depression, you’ll want to structure your diet to avoid high-GI foods while leaning more heavily on medium- and especially low-GI foods, with an emphasis on good sources of whole grains and fiber such as brown rice, quinoa, steel-cut oatmeal, chia seeds, and blueberries. However, a word of caution: you don’t want to overindulge in medium- or low-GI foods either. A large quantity of any carbs, no matter what their GI, places what is called a high glycemic load on your body. Very simply, the glycemic load of a certain food is a number that estimates how much the food will raise your blood-glucose level after you eat it. Studies show that a high glycemic load can increase your chances of depression as well.

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The take-home message? While you don’t need to cut out carbs completely to improve or avoid depression symptoms, it’s essential to make sure you’re choosing the right carbs and eating them in reasonable quantities. To help out, I’ve included a chart in Appendix A of common foods with low-, medium-, and high-glycemic loads.

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Artificial Sweeteners, Especially Aspartame

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Saccharin (Sweet’N Low), aspartame (NutraSweet), sucralose (Splenda), and stevia (Truvia) are just a few of the most popular artificial sweeteners in use by food manufacturers today. Other lesser-known compounds are erythritol, lactitol, maltitol, sorbitol, and xylitol. These sugar replacements are increasingly common in foods that purport to be “healthy” by helping you cut down on calories.

That’s alarming, because science implicates many artificial sweeteners in depression: one study showed that people who consume artificial sweeteners, mostly via diet drinks, are more depressed than those who don’t consume such beverages.14 Even worse, several studies have demonstrated that artificial sweeteners can be toxic to the brain, altering brain concentrations of mood-regulating neurotransmitters.15

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14. Guo X, Park Y, Freedman ND, et al. Sweetened beverages, coffee, and tea and depression risk among older US adults. Matsuoka Y, ed. PLoS One. 2014;9(4):e94715. doi:10.1371/journal.pone.0094715.

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15. Whitehouse CR, Boullata J, McCauley LA. The potential toxicity of artificial sweeteners. AAOHN Journal. 2008;56(6):251–59; quiz, 260–61; Humphries P, Pretorius E, Naudé H. Direct and indirect cellular effects of aspartame on the brain. European Journal of Clinical Nutrition. 2007;62(4):451–62. doi:10.1038/sj.ejcn.1602866.

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16. Choudhary AK, Lee YY. Neurophysiological symptoms and aspartame: what is the connection? Nutritional Neuroscience. 2017;21(5):306–16. doi:10.1080/1028415x.2017.1288340.

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Aspartame, the primary sweetener in many popular diet drinks, including Diet Coke, has been proven to be particularly damaging. In 2017, a review of the studies on aspartame found that it increases substances in the brain that inhibit the synthesis and release of the “happy” neurotransmitters dopamine, noradrenaline, and serotonin.16

In addition, aspartame causes oxidation, which increases harmful free radicals in the brain. We’ll talk about the damaging effects of oxidation many times throughout the book. Oxidation is a chemical process that releases certain particles known as reactive oxygen species, including free radicals, which are unstable molecules prone to causing havoc in cells.17 At low to moderate concentrations, reactive oxygen species are important to your brain cells because they help to maintain internal chemical balance. However, at higher concentrations, an imbalance between antioxidants (which fight free radicals) and the free radicals themselves triggers a condition called oxidative stress, which can cause cell loss or even brain damage and can render the brain more prone to depression.

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17. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: impact on human health. Pharmacognosy Reviews. 2010;4(8):118. doi:10.4103/0973-7847.70902.

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Not all sweeteners are guaranteed to be harmful. However, there is mounting evidence that other sweeteners beyond aspartame, such as sucralose, could also be causing or worsening depression. A 2018 study showed that sucralose significantly alters gut bacteria in mice, increasing a type of bacteria that other studies show is increased in people who are depressed.18 Sucralose also increases myeloperoxidase activity. Myeloperoxidase is a marker of inflammation, and one study found that twins with a history of depression had levels of myeloperoxidase 32 percent higher than those without depression.19

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18. Rodriguez-Palacios A, Harding A, Menghini P, et al. The artificial sweetener Splenda promotes gut proteobacteria, dysbiosis, and myeloperoxidase reactivity in Crohn’s disease–like ileitis. Inflammatory Bowel Diseases. 2018;24(5):1005–20. doi:10.1093/ibd/izy060; Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain, Behavior, and Immunity. 2015;48:186–94. doi:10.1016/j.bbi.2015.03.016.

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19. Vaccarino V, Brennan M-L, Miller AH, et al. Association of major depressive disorder with serum myeloperoxidase and other markers of inflammation: a twin study. Biological Psychiatry. 2008;64(6):476–83. doi:10.1016/j.biopsych.2008.04.023.

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Fried Foods

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A study in Japan looked at 715 Japanese factory workers and measured their levels of depression and resilience. It also documented their level of fried-food consumption. Sure enough, the research team found that people who consumed more fried foods were more likely to develop depression in their lifetime.20

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20. Yoshikawa E, Nishi D, Matsuoka YJ. Association between frequency of fried food consumption and resilience to depression in Japanese company workers: a cross-sectional study. Lipids in Health and Disease. 2016;15(1). doi:10.1186/s12944-016-0331-3.

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Bad Fats

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Fried foods are likely such mood killers because they’re usually fried in unhealthy fats. In recent years, the conversation around fat in the diet has changed from all fats being unhealthy to a clearer distinction between “bad fats” (for instance, margarine, shortening, and hydrogenated oils) known to cause cardiovascular disease and other woes, and “good fats” (for instance, avocados, almonds, and olive oil) that can help prevent disease and benefit well-being.

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In 2011, Almudena Sánchez-Villegas and her colleagues reported on earlier research in which they had set out to determine if there was an association between fats and depression.21 They enrolled 12,059 Spanish university graduates who were free of depression at the start of the study and had each answer a 136-item food-frequency questionnaire to estimate their consumption of specific culinary fats (olive oil, seed oils, butter, and margarine) in order to determine their intake of different categories of fats—saturated fatty acids, polyunsaturated fatty acids (PUFAs), trans-unsaturated fatty acids (trans fats), and monounsaturated fatty acids (MUFAs). During follow-up visits, participants were asked to note any new onset of depression.

After about six years, 657 new cases of depression were identified. The researchers found that the more trans fats in a participant’s diet, the more likely they were to become depressed. On the other hand, the more MUFAs and PUFAs a participant consumed, the less depressed they were. In terms of individual culinary fats, the researchers concluded that olive oil—which consists largely of MUFA—significantly lowered depression risk.

To prevent or lower your chances of depression, shun all trans fats. Although the Food and Drug Administration banned trans fats in 2018, food manufacturers are permitted a transition period to comply with this regulation, so trans fats can still be found in certain foods including microwave popcorn, frozen pizza, refrigerated biscuit dough, fast food, vegetable shortening, and some margarines.

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21. Sánchez-Villegas A, Verberne L, De Irala J, et al. Dietary fat intake and the risk of depression: the SUN Project. PLoS One. 2011;6(1):e16268.

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MUFAS should make up the majority of the fats in your diet. In addition to olive oil, MUFAs are found in nuts (almonds, walnuts) and nut butters (almond and cashew butter) as well as avocados.

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While PUFAs are better than trans fats, not all sources of PUFAs are the best choices for depression. For example, corn, sunflower, and safflower oil in moderation in your diet may be okay, but in excess they can cause an imbalance in omega-3 and omega-6 fatty acids, which may impact emotional regulation and lead to depression (more on this shortly).22

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22. Ford PA, Jaceldo-Siegl K, Lee JW, Tonstad S. Trans fatty acid intake is related to emotional affect in the Adventist Health Study-2. Nutrition Research. 2016;36(6):509–517. doi:10.1016/j.nutres.2016.01.005; Appleton KM, Rogers PJ, Ness AR. Is there a role for n-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials. Nutrition Research Reviews. 2008;21(1):13–41. doi:10.1017/s0954422408998620.

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Added Nitrates

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Used as a preservative and to enhance color in deli slices and cured meats like bacon, salami, and sausage, nitrates may be connected with depression.23 One recent study even suggests that nitrates can alter gut bacteria in such a way as to tip the scales toward bipolar disorder.24 If you simply can’t live without salami and sausages, seek out those containing buckwheat flour, which is used as a filler. Buckwheat flour contains important antioxidants that will counter some of the negative health effects of these meats.25

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23. Suzuki E, Yagi G, Nakaki T, Kanba S, Asai M. Elevated plasma nitrate levels in depressive states. Journal of Affective Disorders. 2001;63(1–3):221–24. doi:10.1016/s0165-0327(00)00164-6.

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24. Khambadkone SG, Cordner ZA, Dickerson F, et al. Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats. Molecular Psychiatry. July 2018. doi:10.1038/s41380-018-0105-6.

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25. Park W, Kim J-H, Ju M-G, et al. Enhancing quality characteristics of salami sausages formulated with whole buckwheat flour during storage. Journal of Food Science and Technology. 2016;54(2):326–32. doi:10.1007/s13197-016-2465-8.

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Foods Rich in Omega-3 Fatty Acids

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We already discussed good fats for depression earlier in the chapter, but I want to give special attention to the importance of omega-3 fatty acids. Omega-3s are crucial to mental health, and we will discuss their benefits over the course of the book.

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Omega-3s are important for normal body metabolism—they are a vital part of cell membranes and provide the starting point for making the hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. But since we cannot produce them on our own, we must get our omega-3s from our diet. This is why we call them essential fats.

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The three main omega-3 fatty acids are alpha-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). All three are important to the body, performing a number of tasks, especially in cell membranes. EPA and DHA are the two omega-3s that play the most critical role in mood disorders, so it’s particularly important to ensure that you get enough of them.

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While there is some argument about the importance of omega-3s in the fight against depression, most studies suggest they are instrumental, including a 2016 meta-analysis of thirteen randomized controlled trials of 1,233 patients with major depressive disorder. It found a beneficial overall effect of omega-3s in patients with major depressive disorder, especially in participants taking higher amounts of EPA and in those taking antidepressants.26

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26. Mocking RJT, Harmsen I, Assies J, Koeter MWJ, Ruhé HG, Schene AH. Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Translational Psychiatry. 2016;6(3):e756. doi:10.1038/tp.2016.29.

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Omega-3s promote brain health by lowering inflammatory markers and protecting neurons from excessive inflammation. The key is to maintain a healthy balance between omega-3s and omega-6s, which are found in different foods. In a typical Western diet, omega-6s are quite common, while omega-3s are much rarer, leading to an omega-6 to omega-3 ratio of somewhere around 15 to 1. The ideal ratio is more like 4 to 1.27 That means most Americans need to cut down on omega-6s while eating more omega-3s.

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27. Simopoulos A. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine and Pharmacotherapy. 2002;56(8):365–79. doi:10.1016/s0753-3322(02)00253–6.

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Indeed, studies have shown that people who consume foods high in omega-6 fatty acids have more than four times the risk of depression compared to those who consume foods high in omega-3s. This means that eating foods high in omega-6s like full-fat cheese, high-fat cuts of red meat, corn oil, and palm oil may increase your chances of depression. On the contrary, eating foods high in omega-3s like fatty fish, walnuts, vegetable oils, and dark, leafy vegetables may protect you against depression.

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The very best source of omega-3s, especially EPA and DHA, is fish. In particular, cold-water fatty fish, such as salmon, mackerel, tuna, herring, and sardines, contain high amounts of omega-3s. Fish with a lower fat content, such as bass, tilapia, cod, and shellfish, aren’t quite as rich in omega-3s but still have significant amounts. Farmed fish usually have higher levels of EPA and DHA than wild-caught fish, but it depends on the food they are fed. That’s because fish themselves do not actually make the omega-3s. Instead, they are found in microalgae. When the fish consume phytoplankton, which consumes microalgae, they accumulate omega-3s in their tissues.

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Omega-3s can also be found in other foods, though nothing is as good a source as fatty fish. Grass-fed beef contains more omega-3s than commercial beef. Alpha-linolenic acid is available from plant sources like edamame, walnuts, and chia seeds, and there are an increasing number of omega-3-fortified foods on the market, especially eggs, milk, and yogurt.

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While canola oil is far from a perfect source of omega-3s, its ratio of omega-6 to omega-3 is roughly 2 to 1, making it a natural choice for a healthier alternative to similar oils.

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Foods Rich in Helpful Vitamins