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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

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Many vitamins play key roles in preventing and easing depression. The most important are folate (B9) and B12. Their functions in the body are inextricably linked: a deficiency in vitamin B12 results in a folate deficiency, which can ultimately contribute to a loss of brain cells, chiefly those located in the hippocampus. Termed “hippocampal atrophy,” this loss of brain cells is associated with depression. The hippocampus is a critical brain structure that plays an important role in learning and memory, so depressed patients may lose their ability to learn new ways to cope with their stress.

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In patients with folate deficiency, depression is the most common symptom.28 In fact, studies have demonstrated that the higher one’s folate level, the lower one’s level of depression.29 In addition to its role in the hippocampus, folate may also affect serotonin synthesis, and in depression, serotonin is often low.30

Hence, both vitamin B12 and folate should be optimized to prevent or treat depression. Enjoy ample amounts of legumes, citrus fruits, bananas, avocados, leafy green and cruciferous vegetables, asparagus, nuts and seeds, and fish and shellfish.

Vitamins B1 (thiamine) and B6 (pyridoxine) are also key for preventing and easing depression, as they help the brain produce and synthesize the neurotransmitters involved in mood regulation. These vitamins are abundant in the foods mentioned in the previous paragraph, as well as in soybeans and whole grains.

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28. Alpert JE, Fava M. Nutrition and depression: the role of folate. Nutrition Reviews. 2009;55(5):145–49. doi:10.1111/j.1753-4887.1997.tb06468.x.

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29. Beydoun MA, Shroff MR, Beydoun HA, Zonderman AB. Serum folate, vitamin B-12, and homocysteine and their association with depressive symptoms among U.S. adults. Psychosomatic Medicine. 2010;72(9):862–73. doi:10.1097/psy.0b013e3181f61863.

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30. Albert PR, Benkelfat C, Descarries L. The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philosophical Transactions of the Royal Society B: Biological Sciences. 2012;367(1601):2378–81. doi:10.1098/rstb.2012.0190.

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Vitamin A facilitates proper brain function such as the growth and adaptation of neurons.31 As with vitamin B12, a deficiency of vitamin A may result in shrinkage of certain brain areas, disturbing how the brain responds to stress.32 In 2016 a study found that vitamin A can significantly improve fatigue and depression in multiple sclerosis patients.33 However, too much retinoic acid (a metabolite of vitamin A) has also been associated with depression and suicide.34 The amount of vitamin A you would have to consume to suffer these ill effects is far beyond what you will eat in a healthy, varied diet, so feel free to eat vitamin A–rich foods such as sweet potatoes, carrots, spinach, and black-eyed peas.

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31. Olson CR, Mello CV. Significance of vitamin A to brain function, behavior and learning. Molecular Nutrition and Food Research. 2010;54(4):489–95. doi:10.1002/mnfr.200900246.

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32. Misner DL, Jacobs S, Shimizu Y, et al. Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity. Proceedings of the National Academy of Sciences. 2001;98(20):11714–19. doi:10.1073/pnas.191369798.

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33. Bitarafan S, Saboor-Yaraghi A, Sahraian MA, et al. Effect of vitamin A supplementation on fatigue and depression in multiple sclerosis patients: a double-blind placebo-controlled clinical trial. Iranian Journal of Allergy, Asthma, and Immunology. 2016;15(1):13–19.

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34. Bremner JD, McCaffery P. The neurobiology of retinoic acid in affective disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2008;32(2):315–31. doi:10.1016/j.pnpbp.2007.07.001.

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Vitamin C is important for proper brain functioning, as it’s responsible for the regulation of neurotransmitter synthesis.35 Several observational studies have suggested a relationship between low levels of vitamin C and depression.36 Get your vitamin C from citrus fruits, cantaloupe, strawberries, and cruciferous vegetables including broccoli, cauliflower, and Brussels sprouts.

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35. Pullar J, Carr A, Bozonet S, Vissers M. High vitamin C status is associated with elevated mood in male tertiary students. Antioxidants. 2018;7(7):91. doi:10.3390/antiox7070091.

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36. Gariballa S. Poor vitamin C status is associated with increased depression symptoms following acute illness in older people. International Journal for Vitamin and Nutrition Research. 2014;84(1–2):12–17. doi:10.1024/0300-9831/a000188.

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We will talk about vitamins many times throughout the book, so if you need a refresher on what vitamins perform which brain functions, and what foods contain those vitamins, you can refer to Appendix B.

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Foods Rich in Iron and Other Helpful Minerals

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In the brain, iron helps make up the covering that protects neurons and helps control the synthesis of chemicals and chemical pathways involved in mood.37 In fact, a large concentration of iron is found in the basal ganglia, a collection of brain cells that have been implicated in depression.38 In clinical studies, low iron levels and depression have been linked.39 Good food sources of iron include shellfish, lean red meats and organ meats (in moderation), legumes, pumpkin seeds, broccoli, and dark chocolate (though any sweet should be eaten in moderation).

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37. Kim J, Wessling-Resnick M. Iron and mechanisms of emotional behavior. Journal of Nutritional Biochemistry. 2014;25(11):1101–7. doi:10.1016/j.jnutbio.2014.07.003.

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38. Pillay S. A quantitative magnetic resonance imaging study of caudate and lenticular nucleus gray matter volume in primary unipolar major depression: relationship to treatment response and clinical severity. Psychiatry Research: Neuroimaging. 1998;84(2–3):61–74. doi:10.1016/s0925-4927(98)00048-1.

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Magnesium is also important for proper brain function. The first report of magnesium treatment for agitated depression was published in 1921, and it showed success in a whopping 220 out of 250 cases.40 Since then, countless studies have suggested that depression is related to magnesium deficiency. Several case studies, in which patients were treated with 125–300 mg of magnesium, have demonstrated rapid recovery from major depression, often in less than a week. How can you get enough magnesium in your diet? Eat more avocados, nuts and seeds, legumes, whole grains, and some omega-3-rich fish (such as salmon and mackerel).

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39. Hidese S, Saito K, Asano S, Kunugi H. Association between iron-deficiency anemia and depression: a web-based Japanese investigation. Psychiatry and Clinical Neurosciences. 2018;72(7):513–21. doi:10.1111/pcn.12656.

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40. Eby GA, Eby KL, Murk H. Magnesium and major depression. In: Vink R, Nechifor M, eds. Magnesium in the Central Nervous System [internet]. Adelaide, Australia: University of Adelaide Press; 2011. Available from https://www.ncbi.nlm.nih.gov/books/NBK507265/.

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When it comes to potassium, the picture is not as clear, but some studies have shown that higher potassium intake can improve mood.41 Sweet potatoes, bananas, mushrooms, oranges, peas, and cucumbers are all high in potassium.

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41. Widmer J, Mouthon D, Raffin Y, et al. Weak association between blood sodium, potassium, and calcium and intensity of symptoms in major depressed patients. Neuropsychobiology. 1997;36(4):164–71. doi:10.1159/000119378; Torres SJ, Nowson CA, Worsley A. Dietary electrolytes are related to mood. British Journal of Nutrition. 2008;100(5):1038–45. doi:10.1017/s0007114508959201.

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Most evidence strongly supports a positive association between zinc deficiency and the risk of depression, with zinc supplements reducing depressive symptoms.42 A meta-analysis of seventeen studies found that blood zinc concentrations were lower in depressed subjects than in control subjects.43 Zinc probably helps because it reduces brain inflammation.44 Find high concentrations of zinc in seafood (especially cooked oysters), lean beef, and poultry, with lower amounts found in beans, nuts, and whole grains.

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42. Wang J, Um P, Dickerman B, Liu J. Zinc, magnesium, selenium and depression: a review of the evidence, potential mechanisms and implications. Nutrients. 2018;10(5):584. doi:10.3390/nu10050584.

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43. Swardfager W, Herrmann N, Mazereeuw G, Goldberger K, Harimoto T, Lanctôt KL. Zinc in depression: a meta-analysis. Biological Psychiatry. 2013;74(12):872–78. doi:10.1016/j.biopsych.2013.05.008.

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44. Szewczyk B, Kubera M, Nowak G. The role of zinc in neurodegenerative inflammatory pathways in depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2011;35(3):693–701. doi:10.1016/j.pnpbp.2010.02.010.

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Finally, several studies have also suggested that a diet high in selenium significantly improves mood scores.45 Brazil nuts are packed with this nutrient.

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45. Finley JW, Penland JG. Adequacy or deprivation of dietary selenium in healthy men: clinical and psychological findings. Journal of Trace Elements in Experimental Medicine. 1998;11(1):11–27. doi:10.1002/(sici)1520-670x(1998)11:1<11::aid-jtra3>3.0.co;2-6.

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Again, if you need a quick reference for what foods contain these minerals, see Appendix B.

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Seasonings, Spices, and Herbs

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In general, one important benefit of spices is their antioxidant properties—in other words, they help the brain fight off harmful free radicals and therefore prevent oxidative stress, which can damage tissues. There is a measure of spices’ antioxidant capacities called ORAC (oxygen radical absorbance capacity). I’ve included an ORAC chart in Appendix C showing which spices have the most antioxidant benefits. Make sure to prioritize those in your cooking as much as possible.

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Saffron: In 2013, a meta-analysis of five previously published randomized controlled trials looked at the effects of saffron supplementation on symptoms of depression among participants with major depressive disorder.46 In all these trials, researchers found that saffron supplementation significantly reduced depression symptoms compared to the placebo controls. A study in 2017 demonstrated that 15 mg of saffron was as effective as 20 mg of Prozac in decreasing depressive symptoms! Apparently saffron’s secret power was known to Christopher Catton, a nineteenth-century English herbalist who once said, “Saffron has power to quicken the spirits, and the virtue thereof pierces by and by to the heart, provoking laughter and merriment.”47 While its precise mechanism of action is not known, in animals saffron increases levels of the good-mood neurotransmitters glutamate and dopamine.

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46. Hausenblas HA, Saha D, Dubyak PJ, Anton SD. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. Journal of Integrative Medicine. 2013;11(6):377–83. doi:10.3736/jintegrmed2013056.

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47. Saffron. Uses of Herbs website. https://usesofherbs.com/saffron. Accessed November 18, 2019.

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48. Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, Tsatsakis AM. The effects of Crocus sativus (saffron) and its constituents on nervous system: a review. Avicenna Journal of Phytomedicine. 2015;5(5):376–91.

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Per pound, saffron is more expensive than gold, and its flavor can overpower others, so you’ll want to use a sprinkle and not a handful! After blooming a few threads (see San Franciscan Seafood Stew, here), add it to vegetable and rice dishes, such as saffron risotto or biryani. You can also find a supplement or extract, though as always with supplements, consult your doctor before taking it.

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Turmeric: A meta-analysis in 2017 evaluated six clinical trials that tested the active ingredient in turmeric, called curcumin, for depression.49 They concluded that curcumin was significantly more effective than placebo in reducing depressive symptoms. How is it capable of such profound effects? Simply put, it adjusts brain chemistry and protects brain cells against toxic damage that leads to depression.

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49. Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin in depression: a meta-analysis. Journal of the American Medical Directors Association. 2017;18(6):503–8. doi:10.1016/j.jamda.2016.12.071.

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The effective dose is 500–1,000 mg a day. While you will read that 1 teaspoon of turmeric contains about 200 mg of curcumin, that’s not exactly accurate. Because turmeric contains approximately 2 percent curcumin by weight, 1 tablespoon (or 3 teaspoons) which weighs 6.8 grams, really contains about 0.136 grams of curcumin, or 136 mg. For any dish, more than 1 teaspoon of turmeric may be overwhelming, so making a few dishes with a teaspoon or two of turmeric a day is a potential solution: add a touch of turmeric to your soups and stews, or even add it to your smoothie. Make a hot tea with it or add a pinch to your salad dressing. Note that piperine, a constituent found in black pepper, increases the absorption and bioavailability of curcumin by 2,000 percent.50 So when you use turmeric, always add some freshly ground pepper too.

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50. Hewlings S, Kalman D. Curcumin: a review of its effects on human health. Foods. 2017;6(10):92. doi:10.3390/foods6100092.

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Oregano: Carvacrol, an active ingredient in oregano, was found to have antidepressant activity in mice.51 Other researchers have also connected carvacrol with neuroprotective and antidepressant effects in animals, although to date, there are no such studies in humans. That said, I believe it’s likely to help protect brain tissue. Commonly used in many cuisines, it’s a staple ingredient in my favorite Greek dressing, used to marinate olives and feta cheese, and delicious on oven-roasted vegetables.

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51. Melo FHC, Moura BA, de Sousa DP, et al. Antidepressant-like effect of carvacrol (5-isopropyl-2-methylphenol) in mice: involvement of dopaminergic system. Fundamental and Clinical Pharmacology. 2011;25(3):362–67. doi:10.1111/j.1472-8206.2010.00850.x.

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I’ll discuss lavender, passionflower, and chamomile in detail while discussing anxiety in chapter 3, but know that these herbs can all be helpful for depression too.52 They’re easiest enjoyed as teas.

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52. Yeung KS, Hernandez M, Mao JJ, Haviland I, Gubili J. Herbal medicine for depression and anxiety: a systematic review with assessment of potential psycho-oncologic relevance. Phytotherapy Research. 2018;32(5):865–91. doi:10.1002/ptr.6033.

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I know that it may feel a bit overwhelming imagining yourself standing in a busy grocery aisle trying to remember exactly which foods are highest in which nutrients.

An even easier way to keep straight what you should and should not eat when fighting depression is to follow a broad diet that naturally steers you toward food that is healthy for your brain and away from food that can hinder your mood. Luckily, such a diet already exists!

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THE MEDITERRANEAN EATING PATTERN

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While the Mediterranean diet wasn’t formulated expressly with mental health in mind, it incorporates all the depression-busting foods just mentioned, and in healthy ratios to help you achieve the nutrient balance needed for optimal brain functioning and mood regulation. And, of course, it’s healthy for your body in many other ways.

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As first described in 1957 by physiologists Ancel Keys and Francisco Grande Covián, and then refined by scientific studies that evaluated the impact of this way of eating on health outcomes, some daily foods in the original Mediterranean diet should include:

3–9 servings of vegetables

½–2 servings of fruit

1–13 servings of cereals (bread and other grains, preferably whole grains)

Up to 8 servings of olive oil53

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53. Keys A, Grande F. Role of dietary fat in human nutrition. III. Diet and the epidemiology of coronary heart disease. American Journal of Public Health and the Nation’s Health. 1957;47(12):1520–30.

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While those serving sizes look like broad ranges (particularly for cereals—13 servings of carbs per day is not advisable in modern nutrition), the amounts translate to roughly 2,200 calories a day, broken down as 37 percent total fat (of which 18 percent is monounsaturated and 9 percent is saturated) and 33 grams of fiber.

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Rather than adhering to the strict proportions of the traditional Mediterranean diet, I prefer to have my patients follow the Mediterranean eating pattern (MEP), which confers the same protective effects on depression risk.54 I sometimes describe this way of eating as a “Mediterranean lifestyle,” because my patients often feel the word diet can sound negative. Diet is associated with restriction, while, truly, this dietary approach is all about the delicious foods you can add to your life to enhance your meals and feel better in the process. Plus, when you don’t feel you’re giving up food, you can avoid what inevitably occurs on restrictive diets: the pendulum swinging back, where you end up overeating the shunned foods anyway. The MEP is a plant-based diet that’s abundant in locally grown seasonal fruits and vegetables and other foods that are minimally processed (e.g., beans, nuts, whole grains). Sweets are limited, and only high-quality fats are acceptable, with olive oil being the primary source of fat. The MEP includes low to moderate dairy intake, and protein is mainly seafood, with red meat and eggs consumed in smaller quantities and with low frequency. Wine is consumed in low to moderate amounts with meals, and herbs and spices are used instead of salt to add flavor to foods. In fact, there is plenty of flexibility with flavors. I always try to adapt the Mediterranean lifestyle to a patient’s culture and tastes, so, for example, I might suggest South Asian recipes for chickpeas or adding Mexican oregano and fajita spices to hummus, depending on what the patient loves to eat.

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54. Boucher JL. Mediterranean eating pattern. Diabetes Spectrum. 2017;30(2):72–76. doi:10.2337/ds16-0074.

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It’s worth noting that there is some controversy about whether the actual diet of the Mediterranean region can be adapted to other parts of the world, as the food preparation and sources of food differ.55 But I believe it can, since the composition of the diet is much more important than preparation or flavors. After all, the antidepressant mechanism of the Mediterranean diet is in large part due to its emphasis on consumption of fruits and vegetables—produce contains high levels of antioxidants that reduce oxidative stress and may, in turn, reduce neuron damage—and olive oil, which is rich in antioxidants and other brain-healthy compounds.56 Nutrient-dense fruits and veggies and high-quality olive oils are now more readily available in supermarkets and online. And of course, fish, nuts, and whole grains can be found at many grocery stores or farmers’ markets as well.

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55. Hoffman R, Gerber M. Evaluating and adapting the Mediterranean diet for non-Mediterranean populations: a critical appraisal. Nutrition Reviews. 2013;71(9):573–84. doi:10.1111/nure.12040.

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56. Harasym J, Oledzki R. Effect of fruit and vegetable antioxidants on total antioxidant capacity of blood plasma. Nutrition. 2014;30(5):511–17. doi:10.1016/j.nut.2013.08.019; Battino M, Ferreiro MS. Ageing and the Mediterranean diet: a review of the role of dietary fats. Public Health Nutrition. 2004;7(7):953–58.

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Foods to Embrace:

Probiotics: Yogurt with active cultures, tempeh, miso, natto, sauerkraut, kefir, kimchi, kombucha, buttermilk, and certain cheeses.

Prebiotics: Beans, oats, bananas, berries, garlic, onions, dandelion greens, asparagus, Jerusalem artichokes, and leeks.

Low-GI carbohydrates: Brown rice, quinoa, steel-cut oatmeal, and chia seeds.

Medium-GI foods, in moderation: Honey, orange juice, and whole-grain bread.

Healthy fats: Monounsaturated fats like olive oil, nuts, nut butters, and avocados.

Omega-3 fatty acids: Fish, especially fatty fish like salmon, mackerel, tuna, herring, and sardines.

Vitamins B9, B12, B1, B6, A, and C.

Minerals and micronutrients: Iron, magnesium, potassium, zinc, and selenium.

Spices: Saffron and turmeric.

Herbs: Oregano, lavender, passionflower,

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Foods to Avoid:

Sugar: Baked goods, candy, soda, or anything sweetened with sugar or high-fructose corn syrup.

High-GI carbs: White bread, white rice, potatoes, pasta, and anything else made from refined flour.

Artificial sweeteners: Aspartame is particularly harmful, but also saccharin, sucralose, and stevia in moderation and with caution.

Fried foods: French fries, fried chicken, fried seafood, or anything else deep-fried in oil.

Bad fats: Trans fats such as margarine, shortening, and hydrogenated oils are to be avoided totally; omega-6 fats such as vegetable, corn, sunflower, and safflower oil should only be consumed in moderation.

Nitrates: An additive used in bacon, salami, sausage, and othercured meats.

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CHAPTER THREE

Anxiety: Fermented Foods, Dietary Fiber, and the Tryptophan Myth

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THE ANXIOUS GUT

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In 2018, Gilliard Lach and his colleagues shed light on the physiological connection between anxiety disorders and bowel issues.2 Their work centered around gut peptides, short chains of amino acids that are used by your body as signaling molecules, carrying information between the gut and the brain. In the gut, specialized cells called enteroendocrine cells produce more than twenty signaling molecules, including peptides.3 The specific types of signaling molecules that are created are determined by your gut bacteria. By manipulating the gut bacteria of mice, and then monitoring the corresponding change in various kinds of peptides present in the guts and brains of the mice, Lach and his team were able to track how changes in the gut microbiome influenced symptoms of anxiety, proving that there is a profound connection between the two. Though the researchers weren’t able to make any conclusions about how this knowledge could be applied to microbiome-based therapeutic strategies to combat anxiety in humans, that’s certainly a possibility down the road.

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2. Lach G, Schellekens H, Dinan TG, Cryan JF. Anxiety, depression, and the microbiome: a role for gut peptides. Neurotherapeutics. 2017;15(1):36–59. doi:10.1007/s13311-017-0585-0.

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One part of the brain that is especially affected by changes in the gut microbiome is the amygdala, a structure found deep in the brain that is a key part of the circuit that goes awry when you are anxious.4 In fact, the connection between the microbiome and amygdala development is so strong that some researchers think we should be targeting the microbiome to stabilize amygdala activation and reduce anxiety.

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3. Dockray GJ. Gastrointestinal hormones and the dialogue between gut and brain. Journal of Physiology. 2014;592(14):2927–41. doi:10.1113/jphysiol.2014.270850.

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4. Liberzon I, Duval E, Javanbakht A. Neural circuits in anxiety and stress disorders: a focused review. Therapeutics and Clinical Risk Management. January 2015:115. doi:10.2147/tcrm.s48528.

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Research has shown that germ-free mice (meaning they lack all microorganisms and therefore have no gut microbiome) have larger amygdalae than mice with normal microbiomes.5 The amygdala is also hyperactive, working overtime in an unhealthy way.6 When it comes to amygdalae, bigger and more active is most definitely not better; in humans, a hyperactive amygdala makes it difficult to control your emotions, as if your brain has an alarm that is constantly going off.7 If the lack of gut bacteria can so profoundly influence the amygdala’s form and function, that’s a strong sign that the microbiome plays an important role in brain health.

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5. Luczynski P, Whelan SO, O’Sullivan C, et al. Adult microbiota-deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus. Gaspar P, ed. European Journal of Neuroscience. 2016;44(9):2654–66. doi:10.1111/ejn.13291.

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6. Hoban AE, Stilling RM, Moloney G, et al. The microbiome regulates amygdala-dependent fear recall. Molecular Psychiatry. 2017;23(5):1134–44. doi:10.1038/mp.2017.100.

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7. Cowan CSM, Hoban AE, Ventura-Silva AP, Dinan TG, Clarke G, Cryan JF. Gutsy moves: the amygdala as a critical node in microbiota to brain signaling. BioEssays. 2017;40(1):170–72. doi:10.1002/bies.201700172.

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In 2004, Nobuyuki Sudo and his colleagues found that germ-free mice also have an exaggerated hypothalamic-pituitary-adrenal axis (HPA-axis) response to stress.8 Incredibly, the introduction of just one specific bacterial species into the mice’s microbiome reversed this. It amazes me that changing just one bacterial species—one among a multitude in the gut—can improve how an organism responds to stress!

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8. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. Journal of Physiology. 2004;558(1):263–75. doi:10.1113/jphysiol.2004.063388.

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If you’re doubtful that the brains of mice have much overlap with your stressful human life, rest assured that recent human studies have found similar results. In 2018, a study compared the microbiota in people with generalized anxiety disorder to those of healthy controls.9 They found that the patients with generalized anxiety disorder had very different bacteria, which were both sparser and less diverse than those in their healthy counterparts. Specifically, bacteria that produce short-chain fatty acids—like the peptides we just discussed, which are a sign of a healthy gut—were scarce, and there was an overgrowth of “bad” bacteria. That’s another clear example of how gut health affects brain health.

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9. Jiang H, Zhang X, Yu Z, et al. Altered gut microbiota profile in patients with generalized anxiety disorder. Journal of Psychiatric Research. 2018;104:130–36. doi:10.1016/j.jpsychires.2018.07.007.

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An interesting aspect of that study was that simply treating the anxiety disorder through nondietary methods did not cause a corresponding change in the patients’ gut bacteria. In other words, while the gut has immense influence on the brain’s behavior, the opposite may not be true—treating mental symptoms with antianxiety medication or psychotherapy doesn’t mean that the imbalances in your gut will automatically fall in line. In order to address the root of the problem, you have to target the actual bacteria too.

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Finally, irregularities in your microbiome can weaken your gut wall, which usually serves as a barrier preventing bacterial metabolites and molecules from entering the bloodstream.10 Since a weakened gut wall allows bacteria to leak through the gut lining and into the blood circulation (and even into the brain), this is called leaky gut syndrome. While there are certainly compounds that need to travel into and out of our gut, in general we want to keep the bacteria of our microbiome confined there. When bacteria are allowed to escape, they can cause damage all over the body, including in the brain. For instance, we have evidence that a component of the bacterial cell wall called lipopolysaccharide causes anxiety-like behaviors in mice.11

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10. Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E, Wakefield S. Gut microbiota’s effect on mental health: the gut-brain axis. Clinics and Practice. 2017;7(4). doi:10.4081/cp.2017.987.

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11. Perna G, Iannone G, Alciati A, Caldirola D. Are anxiety disorders associated with accelerated aging? A focus on neuroprogression. Neural Plasticity. 2016;2016:1–19. doi:10.1155/2016/8457612.

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Bowel Disorders

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Given this constant interaction between your gut and your brain, it’s no surprise that there is a strong correlation between anxiety and bowel disorders. Up to 60 percent of patients with anxiety have irritable bowel syndrome (IBS).12 IBS is a chronic disorder that causes abdominal pain and changes in bowel habits, without any obvious physical cause. Marisol’s constipation, for example, was a sign of IBS, but the condition can also manifest as gas, bloating, diarrhea, or all of the above. To make matters worse, the more severe the anxiety, the more severe the IBS.13 That means when you have a stressor like hosting Thanksgiving dinner, your symptoms are likely to flare up.

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12. Liu L, Zhu G. Gut–brain axis and mood disorder. Frontiers in Psychiatry. 2018;9. doi:10.3389/fpsyt.2018.00223.

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13. Sarkhel S, Banerjee A, Sarkar R, Dhali G. Anxiety and depression in irritable bowel syndrome. Indian Journal of Psychological Medicine. 2017;39(6):741. doi:10.4103/ijpsym.ijpsym_46_17.

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IBS patients have brain changes too.14 Studies have shown that in IBS sufferers, regions of the brain that usually help us attend to our daily tasks, feel emotions, and manage pain do not function as well as they do in most individuals. These brain abnormalities are similar to what we see in patients who have an anxiety disorder, like panic disorder or generalized anxiety disorder. This correlation implies that IBS and these anxiety disorders affect the gut and the brain in similar ways.

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14. Fadgyas-Stanculete M, Buga A-M, Popa-Wagner A, Dumitrascu DL. The relationship between irritable bowel syndrome and psychiatric disorders: from molecular changes to clinical manifestations. Journal of Molecular Psychiatry. 2014;2(1):4. doi:10.1186/2049-9256-2-4.

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Anxiety also occurs more commonly in people with inflammatory bowel disease (IBD), which includes bowel disorders where there is underlying structural damage to the gut, such as ulcerative colitis and Crohn’s disease. Up to 40 percent of people suffering from these disorders also have troublesome anxiety.

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the Western diet is what you’d typically find in a fast-food meal—the major components are bad fats (saturated fats, trans fats, and unhealthy PUFAs like the vegetable oil commonly used for deep-frying) and high-GI carbs, which means lots of fried food, sweetened drinks (especially those sweetened with high-fructose corn syrup), and lots of red meat. While there’s no question that this diet is bad for your physical health, we’ll see its negative influence on mental health throughout this book. Anxiety is no exception.

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Many animal studies indicate that high-fat and high-carbohydrate diets promote anxiety. For instance, in 2016, neuroscientist Sophie Dutheil and her colleagues demonstrated that rats on a high-fat diet were more prone to diabetes and anxiety.15 In 2017, a research group confirmed that diets rich in saturated fats and fructose increase anxiety-like behaviors in rats.16 And in mice, a lower-calorie diet has been shown to decrease anxiety while improving brain blood

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15. Dutheil S, Ota KT, Wohleb ES, Rasmussen K, Duman RS. High-fat diet induced anxiety and anhedonia: impact on brain homeostasis and inflammation. Neuropsychopharmacology. 2015;41(7):1874–87. doi:10.1038/npp.2015.357.

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16. Gancheva S, Galunska B, Zhelyazkova-Savova M. Diets rich in saturated fat and fructose induce anxiety and depression-like behaviours in the rat: is there a role for lipid peroxidation? International Journal of Experimental Pathology. 2017;98(5):296–306. doi:10.1111/iep.12254.

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17. Parikh I, Guo J, Chuang KH, et al. Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions. Aging. 2016;8(11):2814–26.

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There have been similar findings in humans, with several studies demonstrating that high-carb diets lead to obesity and anxiety.18 While the exact brain chemistry associating high-fat and high-carb diets with anxiety is quite complex, it’s likely that unhealthy diets cause brain serotonin to be reduced in some brain regions, thereby increasing the possibility of anxiety.19 I don’t want to oversimplify, as other genetic and chemical factors certainly play a role in anxiety.20 Still, it’s clear that serotonin levels do play an important role. Perhaps the most valuable takeaway here is that high-fat and high-carb diets can change your brain chemistry, potentially leading to anxiety.

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18. Bray GA, Popkin BM. Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes? Diabetes Care. 2014;37(4):950–56. doi:10.2337/dc13-2085.

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19. Haleem DJ, Mahmood K. Brain serotonin in high-fat diet-induced weight gain, anxiety and spatial memory in rats. Nutritional Neuroscience. May 2019:1–10. doi:10.1080/1028415x.2019.1619983.

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20. Xu L, Xu S, Lin L, et al. High-fat diet mediates anxiolytic-like behaviors in a time-dependent manner through the regulation of SIRT1 in the brain. Neuroscience. 2018;372:237–45. doi:10.1016/j.neuroscience.2018.01.001; Gainey SJ, Kwakwa KA, Bray JK, et al. Short-term high-fat diet (HFD) induced anxiety-like behaviors and cognitive impairment are improved with treatment by glyburide. Frontiers in Behavioral Neuroscience. 2016;10. doi:10.3389/fnbeh.2016.00156.

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Another reason it’s a good idea to avoid the Western diet is that it’s a prime culprit in weight gain and eventually obesity. Obesity is associated with being more anxious, with one study finding that obese people have a 25 percent increased chance of suffering from mood and anxiety disorders.21 The chronic stress of anxiety can also increase visceral fat (fat that is stored in the abdominal cavity and around our organs), type 2 diabetes, and other metabolic complications.22

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21. Simon GE, Von Korff M, Saunders K, et al. Association between obesity and psychiatric disorders in the US adult population. Archives of General Psychiatry. 2006;63(7):824. doi:10.1001/archpsyc.63.7.824.

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22. Kyrou I, Tsigos C. Stress hormones: physiological stress and regulation of metabolism. Current Opinion in Pharmacology. 2009;9(6):787–93. doi:10.1016/j.coph.2009.08.007.

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Obesity also leads to bacterial changes in your gut that lead to increased anxiety. In animal studies, obesity itself is not necessarily linked to anxiety—for example, obese mice were not found to be particularly anxious. However, when you give normal-weight mice microbiota from people on a high-fat diet, they become anxious even though they are not obese.23 That’s a strong indicator that the bacterial changes in your gut that come with obesity are responsible for the increased anxiety. Once again, we see how important our daily diet is in terms of taking care of our gut microbiome and hence the gut-brain balance.

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23. Bruce-Keller AJ, Salbaum JM, Luo M, et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biological Psychiatry. 2015;77(7):607–15. doi:10.1016/j.biopsych.2014.07.012.

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As for how to structure your diet in order to maintain a healthy weight, I encourage you to follow the same principles we discussed with the Mediterranean eating pattern in chapter 2. When I talk about high-fat and high-carb diets, I don’t mean that you have to cut out all fats or all carbs. As we’ve already covered, it’s important to make sure that you are getting plenty of high-quality monounsaturated fatty acids and polyunsaturated fatty acids (especially omega-3s, which we will examine again shortly); low-GI carbohydrates are fine too. Most important is to use portion control to keep your calorie intake reasonable, and to strictly limit the amount of bad fats (such as trans fats and saturated fats), and high-GI carbs (such as refined flour and sugar).

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Caffeine

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Caffeine can feel like a lifeline in a busy world, but it’s important to realize that excess caffeine in your diet can precipitate or worsen anxiety. Caffeine overstimulates regions of the brain that process threat. In 2011 an experimental psychology research study gave fourteen healthy male volunteers either 250 mg of caffeine or placebo capsules.25 They then examined brain blood flow in different regions as subjects looked at threatening or neutral faces. They found that caffeine activated the midbrain periaqueductal gray matter, a brain region that is typically activated when a predator is closing in on you.26 To make things worse, caffeine also shuts down a brain region that typically helps you regulate your anxiety.

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25. Smith JE, Lawrence AD, Diukova A, Wise RG, Rogers PJ. Storm in a coffee cup: caffeine modifies brain activation to social signals of threat. Social Cognitive and Affective Neuroscience. 2011;7(7):831–40. doi:10.1093/scan/nsr058.

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26. Mobbs D, Petrovic P, Marchant JL, et al. When fear is near: threat imminence elicits prefrontal-periaqueductal gray shifts in humans. Science. 2007;317(5841):1079–83. doi:10.1126/science.1144298.

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How much caffeine can you drink before it becomes problematic? Most studies show that less than 100 mg of caffeine has little or no effect on anxiety.27 For between 100 mg and 400 mg/day, the results are mixed; nine studies showed no effect on anxiety, whereas twelve studies have shown significant increases in anxiety. Above 400 mg/day, the majority of studies show a significant increase in anxiety.

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27. Wikoff D, Welsh BT, Henderson R, et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food and Chemical Toxicology. 2017;109:585–648. doi:10.1016/j.fct.2017.04.002.

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Alcohol

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people who are anxious sleep more poorly if they drink alcohol regularly.29 Add the fact that alcohol—and binge drinking—is one of the leading preventable causes of death in the United States, and it’s fair to say that the “relaxation” alcohol provides comes with a significant price.30

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29. Becker HC. Effects of alcohol dependence and withdrawal on stress responsiveness and alcohol consumption. Alcohol Research. 2012;34(4):448–58; Chueh K-H, Guilleminault C, Lin C-M. Alcohol consumption as a moderator of anxiety and sleep quality. Journal of Nursing Research. 2019;27(3):e23. doi:10.1097/jnr.0000000000000300.

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30. Danaei G, Ding EL, Mozaffarian D, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. Hales S, ed. PLoS Medicine. 2009;6(4):e1000058. doi:10.1371/journal.pmed.1000058; Chikritzhs TN, Jonas HA, Stockwell TR, Heale PF, Dietze PM. Mortality and life-years lost due to alcohol: a comparison of acute and chronic causes. Medical Journal of Australia. 2001;174(6):281–84.

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Gluten

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the overall science on anxiety in celiac patients is a little conflicted. In 2011 Donald Smith led a meta-analysis that examined whether people with celiac disease have a higher rate of anxiety than those without it.33 Researchers found that anxiety is neither more common nor more severe in adults with celiac disease than in healthy adults. However, another study demonstrated that after being on a gluten-free diet for one year, patients with celiac disease were less anxious.34 And yet another study demonstrated that being on a gluten-free diet is less helpful in reducing anxiety for women with celiac disease than it is for men.35

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33. Smith DF, Gerdes LU. Meta-analysis on anxiety and depression in adult celiac disease. Acta Psychiatrica Scandinavica. 2011;125(3):189–93. doi:10.1111/j.1600-0447.2011.01795.

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34. Addolorato G. Anxiety but not depression decreases in coeliac patients after one-year gluten-free diet: a longitudinal study. Scandinavian Journal of Gastroenterology. 2001;36(5):502–6. doi:10.1080/00365520119754.

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35. Häuser W. Anxiety and depression in adult patients with celiac disease on a gluten-free diet. World Journal of Gastroenterology. 2010;16(22):2780. doi:10.3748/wjg.v16.i22.2780.

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Not everyone with gluten sensitivity has celiac disease, and even among celiac sufferers, the effect on the brain is complex.36 However, if you’re suffering from anxiety, I do recommend getting tested for celiac disease, or even testing yourself by going on a gluten-free diet temporarily to see if it reduces your symptoms.

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36. Pennisi M, Bramanti A, Cantone M, Pennisi G, Bella R, Lanza G. Neurophysiology of the “celiac brain”: disentangling gut-brain connections. Frontiers in Neuroscience. 2017;11. doi:10.3389/fnins.2017.00498.

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Artificial Sweeteners

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As we saw in chapter 2, when you use artificial sweeteners that have no nutritional value, they can increase “bad” gut bacteria and therefore negatively affect mood and anxiety. Sweeteners like aspartame have been more directly linked with anxiety in research studies and should be avoided, or at the very least used in moderation.37

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37. 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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Dietary Fiber

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In 2018, Andrew Taylor and Hannah Holscher found that diets rich in dietary fiber may reduce the risk of depression, anxiety, and stress.38 Dietary fiber is a broad category of food ingredients that are nondigestible by our natural gut enzymes. However, though our guts themselves can’t break down fiber, different types of gut bacteria can. When dietary fiber can be broken down by bacteria, we call this being “fermentable.” Fermentable dietary fiber promotes the growth of “good” gut bacteria. For example, when dietary fiber is broken down into certain smaller sugar molecules, the “good” bacteria Bifidobacterium and Lactobacillus increase, which has a positive effect on mood by activating brain pathways and nerve signaling that can alleviate anxiety.39

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38. Taylor AM, Holscher HD. A review of dietary and microbial connections to depression, anxiety, and stress. Nutritional Neuroscience. July 2018:1–14. doi:10.1080/1028415x.2018.1493808.

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39. Foster JA, McVey Neufeld K-A. Gut–brain axis: how the microbiome influences anxiety and depression. Trends in Neurosciences. 2013;36(5):305–12. doi:10.1016/j.tins.2013.01.005.

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Fiber can also assist with anxiety by keeping your weight down through a number of mechanisms. Since fiber-rich foods take longer to chew, you tend to eat them more slowly, which means your body has more time to recognize it’s full. Fiber can also fill up your stomach without contributing a lot of calories, which helps you feel more satiated with less food. It also takes a longer time to pass through the stomach and small intestine, which makes you feel full for longer.40

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40. Howarth NC, Saltzman E, Roberts SB. Dietary fiber and weight regulation. Nutrition Reviews. 2009;59(5):129–39. doi:10.1111/j.1753-4887.2001.tb07001.x.

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Dietary fiber also decreases inflammation throughout the body, including the brain. There is considerable evidence that brain (and body) inflammation is elevated in patients with anxiety.41 In 2016 Vasiliki Michopoulos and her colleagues found that people with anxiety disorders have elevated levels of certain markers that denote inflammation.42 Inflammation in the brain has been shown to affect areas that are linked to anxiety (for example, the amygdala), and dietary fiber can help by calming down the brain’s and body’s inflammatory responses.

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41. Salim S, Chugh G, Asghar M. Inflammation in anxiety. In: Advances in Protein Chemistry and Structural Biology. Vol. 88. Oxford: Elsevier; 2012:1–25. doi:10.1016/b978-0-12-398314-5.00001-5.

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42. Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsychopharmacology. 2016;42(1):254–70. doi:10.1038/npp.2016.146.

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43. Felger JC. Imaging the role of inflammation in mood and anxiety-related disorders. Current Neuropharmacology. 2018;16(5):533–58. doi:10.2174/1570159x15666171123201142.

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You’ll find rich dietary fiber in the “five Bs”: beans, brown rice, berries, bran, and baked potato with the skin on. If you have bran and fruit for breakfast and brown rice and beans for lunch, then you’ll have this covered. The “B” you’ll want to eat sparingly is the baked potato—potatoes are high in carbs, and we tend to dress them with high-fat condiments. As we covered earlier, neither a high-carb nor a high-fat diet is good for anxiety.

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Other high-fiber foods include pears, apples, bananas, broccoli, Brussels sprouts, carrots, artichokes, almonds, walnuts, amaranth, oats, buckwheat, and pearl barley.

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Omega-3s

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In 2011, Janice Kiecolt-Glaser and her colleagues tested the effects of omega-3s on sixty-nine medical students, measuring their anxiety levels during lower-stress periods and again just before an exam.44 They found that subjects who were given high levels of omega-3s had 20 percent less anxiety than a control group. What’s more, the high-omega-3 group had 14 percent less inflammation in their bodies (as measured by an inflammation marker called interleukin-6).

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44. Kiecolt-Glaser JK, Belury MA, Andridge R, Malarkey WB, Glaser R. Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial. Brain, Behavior, and Immunity. 2011;25(8):1725–34. doi:10.1016/j.bbi.2011.07.229.

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In 2018, a study found that, specifically, the more omega-3 fatty acid eicosapentaenoic acid people consumed, the less anxiety they had. The study also found that a higher ratio of omega-6s to omega-3s led to increased levels of anxiety. Also in 2018, researchers conducted a meta-analysis of nineteen clinical trials, including 2,240 participants from eleven countries, which showed that omega-3s were associated with a reduction in anxiety symptoms.45

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45. Su K-P, Tseng P-T, Lin P-Y, et al. Association of use of omega-3 polyunsaturated fatty acids with changes in severity of anxiety symptoms. JAMA Network Open. 2018;1(5):e182327. doi:10.1001/jamanetworkopen.2018.2327.

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In general, the reduction in anxiety caused by omega-3s is thought to occur via anti-inflammatory and neurochemical mechanisms that affect the brain.46 One potential mechanism for the beneficial effects of omega-3s may occur via the brain’s dopamine pathway. When the brain is inflamed, IL-1, an inflammatory marker, can increase dopamine levels in the nucleus accumbens, a collection of brain cells implicated in human anxiety. Studies have shown that omega-3s can suppress this effect in both animals and humans.47

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46. Su K-P, Matsuoka Y, Pae C-U. Omega-3 polyunsaturated fatty acids in prevention of mood and anxiety disorders. Clinical Psychopharmacology and Neuroscience. 2015;13(2):129–37. doi:10.9758/cpn.2015.13.2.129.

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47. Song C, Li X, Kang Z, Kadotomi Y. Omega-3 fatty acid ethyl-eicosapentaenoate attenuates IL-1β-induced changes in dopamine and metabolites in the shell of the nucleus accumbens: involved with PLA2 activity and corticosterone secretion. Neuropsychopharmacology. 2006;32(3):736–44. doi:10.1038/sj.npp.1301117; Healy-Stoffel M, Levant B. N-3 (omega-3) fatty acids: effects on brain dopamine systems and potential role in the etiology and treatment of neuropsychiatric disorders. CNS and Neurological Disorders—Drug Targets. 2018;17(3):216–32. doi:10.2174/1871527317666180412153612.

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Aged, Fermented, and Cultured Foods

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Fermented foods, like plain yogurt with active cultures and kimchi, are a great source of live bacteria that can enhance healthy gut function and decrease anxiety.48 In the brain, fermented foods may confer several advantages. Fermented foods have improved human cognitive function in several studies.49 A recent review of forty-five studies indicated that fermented foods might protect the brain in animals, improving memory and slowing cognitive decline.50 While the mechanism is not yet clear, three potential effects are highly likely: chemical by-products of intestinal bacteria and bioactive peptides may protect the nervous system; the changing gut bacteria might suppress the stress response through the HPA-axis; and neurotransmitters and “brain tissue builders” such as brain-derived neurotrophic factor, gamma-aminobutyric acid, and serotonin may be increased.

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48. Selhub EM, Logan AC, Bested AC. Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. Journal of Physiological Anthropology. 2014;33(1). doi:10.1186/1880-6805-33-2.

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49. Sivamaruthi B, Kesika P, Chaiyasut C. Impact of fermented foods on human cognitive function—a review of outcome of clinical trials. Scientia Pharmaceutica. 2018;86(2):22. doi:10.3390/scipharm86020022.

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50. Kim B, Hong VM, Yang J, et al. A review of fermented foods with beneficial effects on brain and cognitive function. Preventive Nutrition and Food Science. 2016;21(4):297–309. doi:10.3746/pnf.2016.21.4.297.

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In 2015, Matthew Hilimire and his colleagues questioned 710 people about their fermented-food consumption, social anxiety, and neurotic traits.51 You’ve probably heard the term “neurotic” used in a number of different ways colloquially, but in medical literature, studies show that neurotic people typically are angrier, more anxious, self-conscious, irritable, emotionally unstable, and depressed than the average person.52 Neuroticism is regarded as a fundamental trait that people often inherit from their parents. Hilimire’s study found that eating fermented food frequently correlated with having fewer symptoms of social anxiety in neurotic patients. Taken together with previous studies, the results suggest that fermented foods that contain probiotics may have a protective effect against social anxiety symptoms for those at higher genetic risk.

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51. Hilimire MR, DeVylder JE, Forestell CA. Fermented foods, neuroticism, and social anxiety: an interaction model. Psychiatry Research. 2015;228(2):203–8. doi:10.1016/j.psychres.2015.04.023.

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52. Widiger TA, Oltmanns JR. Neuroticism is a fundamental domain of personality with enormous public health implications. World Psychiatry. 2017;16(2):144–45. doi:10.1002/wps.20411.

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Probiotic-rich yogurt can be a powerful part of your diet, but it’s important to note that yogurt that undergoes heat treatment does not have the same benefits. One such example is yogurt-covered raisins—these aren’t going to help your anxiety, as the heat-treated yogurt has no beneficial bacteria left. Also, you should ensure that the yogurt you consume does not have added sugar. Cereal bars that say “made with real yogurt” may contain only small amounts of yogurt powder and will not help your anxiety.

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kefir and sauerkraut, kimchi is one of those fermented foods associated with less social anxiety.

Other sources of fermented foods include kombucha, miso, tempeh, and apple-cider vinegar. You can also ferment vegetables like carrots, cauliflower, green beans, radishes, and broccoli. You can find recipes for okra pickles and miso-glazed sweet potatoes in chapter 11.

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Tryptophan

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Since TRP is a precursor of serotonin, scientists have theorized that a high-tryptophan diet could help raise the low serotonin levels in anxious brains. In animal studies, TRP reaches brain regions that can increase or decrease anxiety.53 In humans, taking a supplement of purified TRP will increase brain serotonin.54

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53. Silva LCA, Viana MB, Andrade JS, Souza MA, Céspedes IC, D’Almeida V. Tryptophan overloading activates brain regions involved with cognition, mood and anxiety. Anais da Academia Brasileira de Ciências. 2017;89(1):273–83. doi:10.1590/0001-3765201720160177.

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54. Young SN. How to increase serotonin in the human brain without drugs. Journal of Psychiatry and Neuroscience. 2007;32(6):394–99.

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In 2014, Glenda Lindseth and her colleagues conducted a study to test how a high-TRP diet over four days could change the anxiety levels in study participants.55 Twenty-five healthy individuals were given two diets, with a two-week period in between. The first contained 5 mg/kg of tryptophan (the current US recommended daily allowance) for four days. The second diet contained double that dose for four days. Sure enough, the study found that participants consuming higher levels of tryptophan had significantly less depression, irritability, and anxiety.

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55. Lindseth G, Helland B, Caspers J. The effects of dietary tryptophan on affective disorders. Archives of Psychiatric Nursing. 2015;29(2):102–7. doi:10.1016/j.apnu.2014.11.008.

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although purified TRP increases brain serotonin, foods containing TRP do not.56 This is because tryptophan is actually the least abundant amino acid in protein, and it’s carried into the brain by a transport system that prioritizes other amino acids. So, after the ingestion of a meal containing protein, tryptophan gets crowded out, keeping it from crossing over into the brain.

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56. Wurtman RJ, Hefti F, Melamed E. Precursor control of neurotransmitter synthesis. Pharmacological Reviews. 1980;32(4):315–35.

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If this is the case, how do we explain the findings in the Lindseth study? There is a body of evidence that suggests that eating carbohydrates along with protein can increase the tryptophan available to the brain.57 When you eat carbohydrates (like the mashed potatoes at Thanksgiving), the body produces insulin. This insulin diverts other amino acids to your muscles but leaves tryptophan untouched. As a result, tryptophan can cruise through into the brain.

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57. Spring B. Recent research on the behavioral effects of tryptophan and carbohydrate. Nutrition and Health. 1984;3(1–2):55–67. doi:10.1177/026010608400300204.

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Though that sounds logical, some experts question this rationale. So if you’re trying to increase tryptophan, you should probably take it in supplement form. One study showed that, after just fifteen days, purified TRP made participants (particularly men) more agreeable and helped them feel better.58

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58. Aan het Rot M, Moskowitz DS, Pinard G, Young SN. Social behaviour and mood in everyday life: the effects of tryptophan in quarrelsome individuals. Journal of Psychiatry and Neuroscience. 2006;31(4):253–62.

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While the tryptophan benefits of Thanksgiving dinner may be up for debate, there are other sources of tryptophan that may surprise you. For instance, try chickpeas. Some people refer to chickpeas as the ancestors of Prozac. To ensure tryptophan absorption, chickpeas can be made into hummus and combined with whole wheat pita bread, which provides the carbs. For breakfast or a snack, you could also try my recipe for avocado hummus (here) on healthy whole-grain toast.

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Vitamin D

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Studies have demonstrated that adults with depression and anxiety have lower blood levels of vitamin D. In 2019, Siavash Fazelian and his colleagues tested fifty-one women with diabetes and vitamin D deficiency to see whether taking a vitamin D pill every two weeks would change their anxiety levels.59 After sixteen weeks, compared to people who took placebo, people who took the vitamin D were significantly less anxious. In another study, when vitamin D was administered as part of a micronutrient intervention to more than eight thousand people who were depressed and anxious, keeping vitamin D levels high was protective against anxiety.

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59. Fazelian S, Amani R, Paknahad Z, Kheiri S, Khajehali L. Effect of vitamin D supplement on mood status and inflammation in vitamin D deficient type 2 diabetic women with anxiety: a randomized clinical trial. International Journal of Preventive Medicine. 2019;10:17.

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Vitamin D is increasingly recognized as a necessary substance called a neurosteroid, which crosses the blood-brain barrier and enters brain cells.60 While it’s in the brain, it decreases inflammation and toxic destruction of cells and controls the release of nerve growth factor, which is essential for the survival of hippocampal and cortical neurons. The hippocampus plays a crucial role in providing feedback to the HPA-axis when there is stress, and it is also intricately connected to the amygdala.61 The cortex, too, is involved in how we respond to anxiety and stress. Given that abnormalities in all these brain regions may lead to anxiety, vitamin D has an important role in protecting their tissues.

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60. Anjum I, Jaffery SS, Fayyaz M, Samoo Z, Anjum S. The role of vitamin D in brain health: a mini literature review. Cureus. July 2018. doi:10.7759/cureus.2960.

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61. Martin EI, Ressler KJ, Binder E, Nemeroff CB. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Psychiatric Clinics of North America. 2009;32(3):549–75. doi:10.1016/j.psc.2009.05.004; Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2009;35(1):169–91. doi:10.1038/npp.2009.83.

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About 80 percent of our vitamin D comes from exposing our skin to direct sunlight; it’s important to remember that sunlight streaming through our windows does not have the same effect, since glass absorbs all ultraviolet B radiation. With indoor lifestyles being so prevalent today, our skin is often left in the dark. As a result, vitamin D deficiency is occurring in epidemic proportions worldwide.62

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62. Naeem Z. Vitamin D deficiency—an ignored epidemic. International Journal of Health Sciences. 2010;4(1):v–vi.

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Aside from sun exposure, fortified milk and other products such as egg yolk, salmon, sun-dried mushrooms, and cod liver oil are all rich sources of vitamin D. That means that if you have a strict vegan diet, or suffer from milk allergies, you may be more predisposed to vitamin D deficiency, and you need to be extra-conscientious about getting enough of it in your diet or through sun exposure.

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Other Vitamins

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Up to 250 mg of thiamine has been shown to be effective for anxiety.64 In animal studies, thiamine appears to reduce stress-like responses because it protects the hippocampus.65

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64. Cornish S, Mehl-Madrona L. The role of vitamins and minerals in psychiatry. Integrative Medicine Insights. 2008;3:33–42.

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65. Markova N, Bazhenova N, Anthony DC, et al. Thiamine and benfotiamine improve cognition and ameliorate GSK-3β-associated stress-induced behaviours in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2017;75:148–56. doi:10.1016/j.pnpbp.2016.11.001; Vignisse J, Sambon M, Gorlova A, et al. Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels. Molecular and Cellular Neuroscience. 2017;82:126–36. doi:10.1016/j.mcn.2017.05.005.

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Other B vitamins have specific antianxiety properties too. In older women and women suffering from premenstrual stress, vitamin B6 may provide significant relief.66 And many other studies have demonstrated that vitamin B complex can reduce anxiety, possibly by reducing oxidative stress in the brain.67

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66. McCabe D, Lisy K, Lockwood C, Colbeck M. The impact of essential fatty acid, B vitamins, vitamin C, magnesium and zinc supplementation on stress levels in women: a systematic review. JBI Database of Systematic Reviews and Implementation Reports. 2017;15(2):402–53.

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67. Lewis JE, Tiozzo E, Melillo AB, et al. The effect of methylated vitamin B complex on depressive and anxiety symptoms and quality of life in adults with depression. ISRN Psychiatry. 2013;2013:1–7. doi:10.1155/2013/621453.

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The positive effects of vitamins on anxiety extend beyond the vitamin B group as well. In 2012, researchers measured the levels of the antioxidant vitamins A, C, and E in the blood of patients with generalized anxiety disorder.68 They found that levels of all three were low, and after six weeks of supplementation, anxiety symptoms improved. In other studies, multivitamins have been shown to reduce stress and anxiety after twenty-eight days, and in one study, to reduce stress in three hundred people after thirty days of supplementation.69 A 2013 meta-analysis confirmed the stress-relieving effects of multivitamins.70

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68. Gautam M, Agrawal M, Gautam M, Sharma P, Gautam A, Gautam S. Role of antioxidants in generalised anxiety disorder and depression. Indian Journal of Psychiatry. 2012;54(3):244. doi:10.4103/0019-5545.102424.

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69. Carroll D, Ring C, Suter M, Willemsen G. The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological well-being in healthy young male volunteers: a double-blind placebo-controlled trial. Psychopharmacology. 2000;150(2):220–25. doi:10.1007/s002130000406; Schlebusch L, Bosch BA, Polglase G, Kleinschmidt I, Pillay BJ, Cassimjee MH. A double-blind, placebo-controlled, double-centre study of the effects of an oral multivitamin-mineral combination on stress. South African Medical Journal. 2000;90(12):1216–23.

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70. Long S-J, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples. Psychosomatic Medicine. 2013;75(2):144–53. doi:10.1097/psy.0b013e31827d5fbd.

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Magnesium

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In humans, magnesium deficiency is associated with high anxiety levels. When people are anxious while taking a test, they excrete more magnesium than usual in their urine. And when magnesium levels are low, this can worsen anxiety.71

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71. Grases G, Pérez-Castelló JA, Sanchis P, et al. Anxiety and stress among science students. Study of calcium and magnesium alterations. Magnesium Research. 2006;19(2):102–6.

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In 2017, Neil Bernard Boyle and his colleagues reviewed the effects of magnesium supplementation on anxiety.72 They found that magnesium supplementation can help especially if you are vulnerable to anxiety, likely because of the way that magnesium can ease stress responses, changing levels of harmful stress chemicals in the brain.73

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72. Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective anxiety and stress—a systematic review. Nutrients. 2017;9(5):429. doi:10.3390/nu9050429.

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73. Murck H, Steiger A. Mg 2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men—possible therapeutic implications. Psychopharmacology. 1998;137(3):247–52. doi:10.1007/s002130050617.

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Dietary intake of magnesium is poor in Western populations. For example, 68 percent of Americans and 72 percent of middle-aged French adults consume inadequate amounts of magnesium in their diets. Foods rich in magnesium include almonds, spinach, cashews, and peanuts. Cooked black beans, edamame, peanut butter, and avocado also have relatively high amounts of magnesium.

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Most studies show a difference in levels of anxiety after an intake of magnesium over six to twelve weeks.74 As an added bonus, magnesium helps muscle cells relax after contracting. When magnesium levels are low, your muscles may contract too much and cause your body to experience muscle cramps, spasms, or tightness.

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74. Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective anxiety and stress—a systematic review. Nutrients. 2017;9(5):429. doi:10.3390/nu9050429.

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Nutritional and Herbal Supplements

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Certain nutritional and herbal supplements can help you manage anxiety. In 2010, Shaheen Lakhan and Karen F. Vieira explained that there is strong evidence that herbal supplements containing extracts of herbs such as passionflower or kava and combinations of amino acids like L-lysine or L-arginine reduce anxiety.75 Passionflower increases the neurotransmitter gamma-aminobutyric acid, which in turn decreases anxiety. One of the advantages of passionflower over traditional anxiety medications is that it causes less sedation—a frequent side effect of pharmaceutical treatments. Passionflower has been shown to specifically reduce anxiety after surgery too.

Forty-five drops of passionflower liquid extract taken daily or a specific tablet formulation of 90 mg/day has been shown to be effective.

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75. Lakhan SE, Vieira KF. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutrition Journal. 2010;9(1). doi:10.1186/1475-2891-9-42.

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Other foods and nutrients that decrease anxiety include selenium (found in Brazil nuts), potassium-rich foods (e.g., pumpkin seeds), flavonoids (e.g., dark chocolate), and theanine (e.g., green tea).76 Foods that contain high amounts of lysine such as lean beef and lamb, tempeh, seitan, lentils, black beans, and quinoa can also be helpful. On the other hand, avoid wheat bran since it contains phytic acid, which blocks zinc absorption and causes anxiety.

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76. Crichton-Stuart, C. “What are some foods to ease your anxiety?” Medical News Today. August 1, 2018. Retrieved from https://www.medicalnewstoday.com/articles/322652.php.

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When it comes to spices that reduce anxiety, the standout is turmeric. The active ingredient in turmeric, curcumin, decreases anxiety and changes the corresponding brain chemistry, protecting the hippocampus. Curcumin’s positive effect on anxiety has been confirmed by animal studies and three trials in humans.77

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77. Noorafshan A, Vafabin M, Karbalay-Doust S, Asadi-Golshan R. Efficacy of curcumin in the modulation of anxiety provoked by sulfite, a food preservative, in rats. Preventive Nutrition and Food Science. 2017;22(2):144–48; Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin in depression: a meta-analysis. Journal of the American Medical Directors Association. 2017;18(6):503–8. doi:10.1016/j.jamda.2016.12.071.

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Chamomile is an herb that comes from the daisy-like flowers of the Asteraceae plant family. It has been consumed for centuries as a natural remedy for several health conditions, and it has been shown in several studies to help lower anxiety.78 Though it can be taken in capsule form, I recommend getting chamomile the traditional way, in tea. One to 3 cups a day is generally safe unless you are taking blood thinner medications or are about to have surgery. Pregnant women should consult their doctors before consuming chamomile tea.

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78. Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: a randomized clinical trial. Phytomedicine. 2016;23(14):1735–42. doi:10.1016/j.phymed.2016.10.012.

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Oral lavender oil preparation has also been shown in several studies to lower anxiety.79 Lavender oil is available as a supplement, but you can also drink lavender tea or even use lavender in aromatherapy. For supplements I suggest consulting with your doctor first.

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79. Koulivand PH, Khaleghi Ghadiri M, Gorji A. Lavender and the nervous system. Evidence-Based Complementary and Alternative Medicine. 2013;2013:1–10. doi:10.1155/2013/681304.

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Foods to Embrace:

High-fiber foods: Beans, brown rice, berries, bran, pears, apples, bananas, broccoli, Brussels sprouts, carrots, artichokes, almonds, walnuts, amaranth, oats, buckwheat, and pearl barley.

Aged, fermented, and cultured foods: Yogurt, kombucha, miso, tempeh, apple-cider vinegar, and pickled vegetables.

Tryptophan: Turkey, other meats, and chickpeas, especially when combined with carbohydrates.

Vitamins D, B1, B6, A, C, and E.

Minerals: Magnesium, potassium, and selenium.

Spices: Turmeric.

Herbs: Lavender, passionflower, and chamomile.

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Foods to Avoid:

The components of the Western diet: Foods high in bad fats (red meat, fried foods) and high-GI carbs (white bread, white rice, potatoes, pasta, and anything else made from refined flour).

Caffeine: Keep caffeine consumption under 400 mg/day.

Alcohol: For men, stay under 14 drinks per week and no more than 2 drinks in any single day; for women, stay under 7 drinks per week and no more than 1 drink in any single day. By cutting back slowly, you will help lower anxiety.

Gluten: If you have celiac disease or non-celiac gluten sensitivity, avoid all wheat products, such as bread, pizza, pasta, and many alcoholic drinks.

Artificial sweeteners: Aspartame is particularly harmful, but also saccharin. Use sucralose and stevia in moderation and with caution.

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CHAPTER ONE

The Gut-Brain Romance

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Granted, we’ve come a long way from the cold showers and shackles of the seventeenth and eighteenth centuries. In those early barbaric years, “madness” was considered a sinful state, and the mentally ill were housed in prisons. As civilization progressed, mentally ill patients were moved to hospitals.1 The problem is, as we became more and more focused on the troublesome thoughts and emotions of mental illnesses, we stopped noticing that the rest of the body was also involved.

This wasn’t always the case. In 2018, historian Ian Miller pointed out that eighteenth- and nineteenth-century doctors were clued in to the fact that the body’s systems are connected.2 That’s why they talked about the “nervous sympathy” among our different organs.

However, in the late nineteenth century, doctors changed this perspective. As medicine became more specialized, we lost track of the big picture, only looking at single organs to determine what was wrong and what needed fixing.

Of course, doctors did recognize that cancers might spread from one organ to the next, and that autoimmune conditions like systemic lupus erythematosus could affect multiple organs in the body. But they neglected to see that organs that were seemingly quite separate in the body might still profoundly influence one another. Metaphorically speaking, illness could come from a mile away!

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Compounding the problem was that, rather than working collaboratively, physicians, anatomists, physiologists, surgeons, and psychologists competed with one another. As one British doctor wrote in 1956, “There is such a clamour of contestants for cure that the patient who really wants to know is deafened rather than enlightened.”3

This attitude prevails in medicine even today. That’s why so many people are oblivious to the fact that when mental health is affected, the root of the problem is not solely in the brain. Instead, it’s a signal that one or more of the body’s connections with the brain has gone awry.

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Miller I. The gut-brain axis: historical reflections. Microbial Ecology in Health and Disease. 2018;29(2):1542921. doi:10.1080/16512235.2018.1542921.

3. Ibid.

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We know that these connections are quite real. Depression can affect the heart. Pathologies of the adrenal gland can throw you into a panic. Infections darting through your bloodstream can make you seem like you have lost your mind. Maladies of the body frequently manifest as turbulence of the mind.

But while medical illness can cause psychiatric symptoms, we now know that the story goes even deeper. Subtle changes in distant parts of the body can change the brain too. The most profound of these distant relationships is between the brain and the gut. Centuries ago, Hippocrates, the father of modern medicine, recognized this connection, warning us that “bad digestion is the root of all evil” and that “death sits in the bowels.” Now we are figuring out how right he was. Though we are still on the forefront of discovery, in recent years the gut-brain connection has provided one of the richest, most fertile research areas in medical science and the fascinating nexus of the field of nutritional psychiatry.

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Once upon a time, a sperm made its way to an egg. They were not ships passing in the night. They connected. And when the union was successful, you were conceived. Warmly ensconced in your mother’s uterus, you, as this fertilized egg (called a zygote), started to change.

At first, the zygote’s smooth outer surface developed ripples like a mulberry. As time went on, the magical egg, under the spell of biological instructions, started to change its configuration until your baby body took shape. Eventually, after nine long months, you were armed with a heart, gut, lungs, brain, limbs, and other nifty things, ready to announce yourself to life.

But before all that, before you emerged ready to take on the world, before your gut and brain became distinct entities, they were one. They came from the same fertilized egg that gave rise to all the organs in your body.

In fact, the central nervous system, made up of the brain and spinal cord, is formed by special cells known as neural crest cells. These cells migrate extensively throughout the developing embryo, forming the enteric nervous system in the gut. The enteric nervous system contains between 100 million and 500 million neurons, the largest collection of nerve cells in the body. That’s why some people call the gut “the second brain.” And it’s why the gut and brain influence each other so profoundly. Separate though they may appear to be, their origins are the same.

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While your gut and brain are housed in different parts of your body, they maintain more than just a historical connection. They remain physically connected too.

The vagus nerve, also known as the “wanderer nerve,” originates in the brain stem and travels all the way to the gut, connecting the gut to the central nervous system. When it reaches the gut, it untangles itself to form little threads that wrap the entire gut in an unruly covering that looks like an intricately knitted sweater. Because the vagus nerve penetrates the gut wall, it plays an essential role in the digestion of food, but its key function is to ensure that nerve signals can travel back and forth between the gut and the brain, carrying vital information between them. Signals between the gut and brain travel in both directions, making the brain and gut lifelong partners. That is the basis of the gut-brain romance.

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The basis of all body communications is chemical. When you take a pill for a headache, you usually swallow it, right? It enters your mouth, then makes its way to your gut, where it is broken down. The chemicals from the pill travel from your gut to your brain through your bloodstream. And in your brain, they can decrease the inflammation and loosen your tense blood vessels too. When the chemicals you swallow successfully exert their effects on the brain, you feel relief from that pain.

In the same way as the chemicals in that pill, chemicals produced by the gut can also reach your brain. And chemicals produced by your brain can reach your gut. It’s a two-way street.

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In the brain, these chemicals originate from the primary parts of your nervous system (with an assist from your endocrine system): the central nervous system, which comprises the brain and spinal cord; the autonomic nervous system (ANS), which comprises the sympathetic and parasympathetic systems; and the hypothalamic-pituitary-adrenal axis (HPA-axis), which comprises the hypothalamus, pituitary gland, and adrenal gland.

The central nervous system produces chemicals such as dopamine, serotonin, and acetylcholine that are critical for regulating mood and processing thought and emotion. Serotonin, a key chemical deficient in the brains of depressed and anxious people, plays a major role in regulating the gut-brain axis. Serotonin is one of the most buzzed-about brain chemicals because of its role in mood and emotion, but did you know that more than 90 percent of serotonin receptors are found in the gut? In fact, some researchers believe that the brain-serotonin deficit is heavily influenced by the gut,

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The autonomic nervous system (ANS) is in charge of a broad range of essential functions, most of which are involuntary: your heart keeps beating, and you keep breathing and digesting food because of your ANS. When your pupils dilate to take in more light in a dark room, that’s the ANS. Perhaps most crucially for our purposes, when your body is under duress, your ANS controls your fight-or-flight response, an instinctual reaction to threat that sends a cascade of hormonal and physiological responses through your body in dangerous or life-threatening situations. As we’ll see later on, the gut has a profound effect on fight or flight, particularly through the regulation of the hormones adrenaline and noradrenaline (also known as epinephrine and norepinephrine).

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The HPA-axis is another crucial part of the body’s stress machine. It produces hormones that stimulate release of cortisol, the “stress hormone.” Cortisol amps the body up to handle stress, providing a flood of extra energy to deal with difficult situations. Once the threat passes, the cortisol level returns to normal. The gut also plays an important role in cortisol release and is instrumental in making sure the body responds to stress effectively.

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In a healthy body, all these brain chemicals ensure that the gut and brain work smoothly together. Of course, as in all delicate systems, things can go wrong. When chemical over- or underproduction disrupts this connection, the gut-brain balance is thrown into disarray. Levels of important chemicals go out of whack. Moods are upset. Concentration is disrupted. Immunity drops. The gut’s protective barrier is compromised, and metabolites and chemicals that should be kept out of the brain reach the brain and wreak havoc.

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sometimes gets lost in discussions about mental health is a simple truth: the food you eat can have just as profound an effect on your brain as the drugs you take. How can something as basic and natural as eating be as potent as a drug that cost millions of dollars to develop and test? The first part of the answer lies in bacteria.

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Behind the scenes of the gut-brain romance is a huge collection of microorganisms that reside in the gut.4 We call this panoply of different bacterial species the microbiome. The gut microbiome—in both humans and other animals—is another type of romance, with both parties relying on each other for survival. Our guts provide the bacteria with a place to live and thrive, and in return they perform crucial tasks for us that our bodies can’t perform on their own.

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4. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of Gastroenterology. 2015;28(2):203–9.

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The microbiome is made up of many different types of bacteria, with a much greater diversity of species in the gut than anywhere else in the body. Each individual gut can contain up to a thousand different species of bacteria, though most of them belong to two groups—Firmicutes and Bacteroides—which make up about 75 percent of the entire microbiome.

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While we won’t spend too much time discussing individual species in this book, suffice it to say that when it comes to bacteria, there are good guys and bad guys. The microorganisms that inhabit the gut are normally good guys, but it’s inevitable that some bad ones get mixed in. This isn’t necessarily a concern, as your body generally makes sure that the good and bad bacteria stay at the right balance. But if diet, stress, or other mental or physical problems cause changes in gut bacteria, that can cause a ripple effect that leads to many negative health effects.

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The idea that the microbiome plays such an essential role in bodily function is relatively new in medicine (think about how often you’ve heard of bacteria as “germs that will make you sick” rather than as a helpful team of microorganisms that performs a vital service), particularly when it comes to bacteria’s influence on the brain. But over the years, the science has been building that gut bacteria can affect mental function.

About thirty years ago, in one of the most compelling studies that first made us aware that changes in gut bacteria could influence mental function, researchers reported on a series of patients with a kind of delirium (called hepatic encephalopathy) due to liver failure. In hepatic encephalopathy, bacterial “bad guys” produce toxins, and the study showed that these patients stopped being delirious when antibiotics were administered by mouth. That was a clear sign that changing gut bacteria could also change mental function.

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In the years since, we’ve accumulated a huge amount of knowledge about how the gut microbiome affects mental health, and we’ll unpack that knowledge throughout this book. For instance, did you know that functional bowel disorders like irritable bowel syndrome and inflammatory bowel disease also come with mood changes due to bacterial populations being altered?5 Or that some clinicians feel that adding a probiotic as part of a psychiatric medication treatment plan can also help to lower anxiety and depression? Or that if you transfer the gut bacteria of schizophrenic humans into the guts of lab mice, those mice also start to show symptoms of schizophrenia?

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The primary reason gut bacteria have such a profound effect on mental health is that they are responsible for making many of the brain chemicals we discussed in the last section. If normal gut bacteria are not present, production of neurotransmitters such as dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA)—all critically important for the regulation of mood, memory, and attention—is impacted. As we’ll see, many psychiatric disorders are rooted in deficits and imbalances of these chemicals, and many psychiatric drugs are tasked with manipulating their levels. Therefore, if your gut bacteria are intimately involved with producing these vital chemicals, it stands to reason that when your gut bacteria are altered, you risk doing damage to this complex web of body and brain function. That’s a lot of responsibility for a group of microscopic organisms!

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Different collections of bacteria affect brain chemistry differently. For instance, changes in proportions and function of Escherichia, Bacillus, Lactococcus, Lactobacillus, and Streptococcus can result in changes in dopamine levels and may predispose one to Parkinson’s disease and Alzheimer’s disease.6 Other combinations of abnormal gut bacteria may result in abnormally high concentrations of acetylcholine, histamine, endotoxin, and cytokines, which can damage brain tissue.

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6. Giau V, Wu S, Jamerlan A, An S, Kim S, Hulme J. Gut microbiota and their neuroinflammatory implications in Alzheimer’s disease. Nutrients. 2018;10(11):1765. doi:10.3390/nu10111765; Shishov VA, Kirovskaia TA, Kudrin VS, Oleskin AV. Amine neuromediators, their precursors, and oxidation products in the culture of Escherichia coli K-12 [in Russian]. Prikladnaia Biokhimiia i Mikrobiologiia. 2009;45(5):550–54.

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In addition to regulating neurotransmitter levels, there are various other ways in which microbiota influence the gut-brain connection. They are involved in the production of other important compounds like brain-derived neurotrophic factor, which supports the survival of existing neurons and promotes new neuron growth and connections. They influence the integrity of the gut wall and the gut’s barrier function, which protect the brain and the rest of the body from substances that need to be confined to the gut. Bacteria can also have an effect on inflammation in the brain and body, particularly influencing oxidation, a harmful process that results in cellular damage.

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As I mentioned earlier, the gut-brain connection works both ways. So if gut bacteria can influence the brain, it is also true that the brain can change gut bacteria.

All it takes is two hours’ worth of psychological stress to completely change the bacteria in your gut.7 In other words, a tense family Christmas dinner or unusually bad traffic can be enough to upset the balance of your microbiome. The theory is that the ANS and HPA-axis send signaling molecules to gut bacteria when you are stressed, changing bacterial behavior and composition. The results can be damaging. For example, one kind of bacterium changed by stress is Lactobacillus. Normally, it breaks down sugars into lactic acid, prevents harmful bacteria from lining the intestine, and protects your body against fungal infections. But when you are stressed, Lactobacillus fails on all these fronts due to how stress disrupts its functioning, leaving you exposed to harm.

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The brain can also affect the physical movements of the gut (for example, how the gut contracts), and it controls the secretion of acid, bicarbonate, and mucus, all of which provide the gut’s protective lining. In some instances, the brain affects how the gut handles fluid. When your brain is not functioning well—for example, when you have depression or anxiety—all these normal and protective effects on the gut are compromised. As a result, food is not properly absorbed, which in turn has a negative effect on the rest of the body since it’s not getting the nutrients it needs.

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So to recap, your brain needs the proper balance of gut bacteria to make the chemicals it needs to stay stable and healthy. The gut needs your brain to be stable and healthy so that it can maintain the proper balance of gut bacteria. If that cyclical relationship is disrupted, it means trouble for both the gut and the brain. An unhealthy gut microbiome leads to an unhealthy brain, and vice versa.

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A quick illustration of these issues is provided by a survey Mireia Valles-Colomer and her colleagues conducted in April 2019 of more than a thousand people, in which they correlated microbiome features with well-being and depression.8 They found that butyrate-producing bacteria were consistently associated with higher quality-of-life indicators. Many bacteria were also depleted in people with depression, even after correcting for the confounding effects of antidepressants. They also found that when the dopamine metabolite 3,4-dihydroxyphenylacetic acid, which helps gut bacterial growth, is high, mental health is improved. GABA production is disturbed in people with depression too.

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8. Valles-Colomer M, Falony G, Darzi Y, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology. 2019;4(4):623–32. doi:10.1038/s41564-018-0337-x.

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Food influences your brain directly and indirectly.9 When food is broken down by the microbiota into fermented and digested materials, its components directly influence the same kinds of neurotransmitters we’ve been discussing, such as serotonin, dopamine, and GABA, which travel to the brain and change the way you think and feel. When food is broken down, its constituent parts can also pass through the gut wall into the bloodstream, and certain metabolites can act on the brain that way as well.

As we’ve already touched on, food’s most profound effect on the brain is through its impact on your gut bacteria. Some foods promote the growth of helpful bacteria, while others inhibit this growth. Because of that effect, food is some of the most potent mental health medicine available, with dietary interventions sometimes achieving similar results to specifically engineered pharmaceuticals, at a fraction of the price and with few if any side effects.

On the other hand, food can also made you sad—certain food groups and eating patterns can have a negative effect on your gut microbiome and your mental health.

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My own view of where we went wrong is this: psychiatric diagnoses have no statistical validity, and the conditions have no biomarkers of specific diseases.12 “Diagnoses” are simply lists of symptoms. We assume that when a person presents with psychological symptoms, the problem rests solely in the brain. Given what we have reviewed so far, it is clear that other organs such as the gut play a role in how we think and feel. We need to examine the whole person and their lifestyle in order to better treat them.

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12. Liang S, Wu X, Jin F. Gut-brain psychology: rethinking psychology from the microbiota–gut–brain axis. Frontiers in Integrative Neuroscience. 2018;12. doi:10.3389/fnint.2018.00033.

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The problem is bigger than psychiatry, extending to medicine as a whole. Despite the huge number of health issues that relate to diet, it may sound far-fetched, but many patients don’t hear food advice from their doctors, let alone their psychiatrists. Medical schools and residency programs do not teach students how to talk to patients about dietary choices. Nutrition education for doctors is limited.