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Reducing & Preventing Depressive Symptoms with Food

By Harvey Hyman, LPCC

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Reducing and Preventing Depressive Symptoms with Food

At least 40% and as many as 60% of patients with depression do not respond to antidepressant drugs (1)(2). On one level this is not surprising since drug companies don’t need to demonstrate an effect size over .5 to get government approval, which means they don’t have to show that out of 100 people with depression at least 51 will improve because of their drug (3). Rather, all they need demonstrate is that their antidepressant works better than placebo, even by a razor’s edge (3). The scientific explanation for the significant failure level of antidepressants is that  many cases of depression are actually caused by brain inflammation not low serotonin. This has been substantiated by at least two avenues of research. PET scans using radioisotopes show that depressed people average a 30% increase in inflammation of their brain tissue (4). Lab tests of human blood show that depressed people have a significantly  higher level of C-reactive protein which is a well-established marker for brain inflammation (5)(6). 

Research like this has prompted some neuroscientists and psychiatrists to argue it is more effective to target brain inflammation than to increase the supply of neurotransmitters such as serotonin, norepinephrine or dopamine in the brain. During the January 16, 2022, episode of Science Friday on National Public Radio, Dr. David Hellerstein, a Professor of Clinical Psychiatry at Columbia University, spoke about a major shift in the treatment of depression. According to Dr. Hellerstein Big Pharma is no longer investing in the discovery and production of antidepressants like Prozac or Zoloft that target a deficiency of serotonin in the brain. The action is now with startup companies engaged in Phase 3 clinical trials of ketamine and psychedelics like psilocybin which jolt the brain into reorganizing its neural circuitry and creating new circuits that increase human resiliency and thereby contribute to improved mood (7).

Agents like ketamine and psilocybin show real promise but certainly they are not for everyone. Ketamine must be administered by an anesthesiologist or pain medicine specialist with a therapist in the room. Psilocybin scares people who fear they will go on a trip and never come back. 

Brain inflammation and depression are a two-way street in that each contributes to each other. If inflammation in the body and brain could be brought under control than so could depression, the theory goes. Is there a simpler, less expensive, and more inviting way to reduce inflammation in the body and the brain? The answer is yes, and the answer is food which is much cheaper than drugs, does not require a prescription or health insurance and does not have the adverse side effects of antidepressants. There is a relatively new rapidly emerging field called nutritional psychiatry (8). Two nationally recognized academic leaders in this field are Dr. Uma Naidoo at Harvard and Dr. Drew Ramsey at Columbia. Another vigorous advocate of food to improve mood is psychotherapist and nutritionist Julia Ross, the founder and director of the NeuroNutrient Therapy Institute in Mill Valley, CA. 

Much of the information for this article comes from Dr. Naidoo’s book This is Your Brain on Food (9). Dr. Naidoo is a Harvard trained, board certified psychiatrist, a faculty member at Harvard Medical School, a professional chef, and a master’s level nutrition specialist. She is the founder and director of Nutritional and Lifestyle Psychiatry at Massachusetts General Hospital in Boston. In her book Dr. Naidoo has separate chapters on what foods are best to eat to reduce the symptoms of depression, anxiety, PTSD, OCD, bipolar disorder, and schizophrenia. 

From Dr. Naidoo’s perspective the nutritional foundation of good mental health is understanding the gut-brain connection and eating in accord with what she calls a Mediterranean Eating Pattern to keep one’s gut biome healthy. A healthy gut biome will literally feed the brain, keep it in peak health, prevent inflammation, and boost mood. To eat according to MEP is to consume a lot of fresh, local, seasonal fruits and vegetables in their whole form (not peeled and juiced) and drink water not soda, diet soda, beer or alcohol (excepting moderate consumption of red wine) (9). It means eating high-fiber, complex carbs and avoiding foods that contain white sugar, high fructose corn syrup, added sugar, and sugar alcohol, and consuming whole grains rather than white rice and products made with refined white flour such as bread, crackers, and pasta (8). 

So, what exactly is the gut biome? It is a collection of trillions of micro-organisms, mostly bacteria, that reside in your gastro-intestinal system, mainly in your intestines. When the types and amounts of gut bacteria are “good” (which means friendly to gut health) you process and absorb nutrients better, synthesize vitamins better, keep your metabolism and weight at a healthy level, keep your immune system functioning well, and keep your mood good (9). Good gut bacteria even keep the lining of your intestinal tract healthy, kill viruses and fungi that threaten gut health, and seal off tiny leaks in the gut that could lead to conditions like ulcerative colitis, Crohn’s disease or IBS. When the foods you eat kill off the good bacteria all hell breaks loose in your gut biome. The bad bacteria flourish and so does inflammation in the gut and the brain since gut and brain are intimately connected (9). 

How are the gut and brain connected? Through the longest nerve in the body, cranial nerve X known as the vagus nerve. This is the same nerve discussed in so much detail in Stephen Porges’ polyvagal model of mental health that seeks to explain and regulate the fight/flight/freeze response (10). It has long been known that the gut produces 90% of the serotonin in our bodies (11). If you eat foods that kill the good gut bacteria, the supply of serotonin and other neurotransmitters like GABA that keep the brain calm, regulated, and neither over nor under active will dwindle so less will get to the brain via the vagus nerve. Still worse, your gut becomes inflamed and sends inflammatory chemicals to the brain where they dysregulate mood and cause depression. 

Depression and inflammation form a bidirectional loop and frequently co-occur (12). The more depressed you are the more cortisol the HPA (hypothalamic-pituitary-adrenal) axis in your brain secretes you’re your bloodstream and the more your body gets inflamed (13). When the level of cortisol exceeds a threshold point the hippocampus gets overwhelmed and is no longer able to put the brakes on cortisol production (13). The stage is then set for all the wreckage that high cortisol can produce. This includes worsened depression, fatigue, brain fog, cardio-vascular problems, blunting of the immune system with increased infections and slowed healing, weight gain with a protruding belly full of brown fat, thin skin, acne, and more (13). 

So, what are the good foods and why are they good? Good foods promote the growth of friendly gut bacteria in a variety of ways. Probiotics contain living gut friendly bacteria and can reverse both inflammation and its bad effects on mood (9). Foods rich in probiotics include Greek yogurt, sauerkraut, kimchi, tofu, miso, buttermilk, and cheeses such as cheddar, mozzarella, and gouda (9). High fiber foods like seeds, nuts, beans, lentils, bran, flax, whole grain bread, and whole fresh fruits and vegetables are good because fiber feeds good gut bacteria (9). Fruits with lots of fiber are apples and oranges. Veggies that are especially good are leafy greens, broccoli, asparagus, onions, and garlic (9). Foods that contain high levels of Omega 3 essential fatty acids and a good ratio of Omega 3s to Omega 6s, decrease brain inflammation and increase brain health in various ways (9). They help build healthy brain cell membranes and myelin sheaths around the axons that release packets of neurotransmitters across synapses. They also make arterial walls more flexible and thin the blood to prevent clots so the circulation of oxygenated blood to the brain is increased (9). 

Red wine consumed in moderation also has this effect (9), but wine doesn’t mix well with antidepressants and some depressed clients are already having problems with drinking too much, so care must be exercised here. Foods rich in Omega essential fatty acids include cold water fish like tuna, salmon, mackerel, herring, sardines, and anchovies (9). People who live in nations like Italy and Greece on the shores of the Mediterranean generally love to eat these fish. My experience is that many Americans find them too fishy and “gross,” except for tuna fish which they can’t get enough of. I enjoy cooking and have found recipes that make these fish enjoyable. I have tried frying sardines in EVOO (extra virgin olive oil), garlic, and breadcrumbs with lemon juice and then piling them on pasta or rinsing sardines in water and then making a mash of sardines with lemon juice, chopped onions, chopped tomatoes, parsley, oregano, salt, and pepper. Get curious and look for recipes that appeal to you on the Internet. 

Non-animal sources of Omegas are EVOO, seeds, nuts, and beans (9). Some foods reduce inflammation in the brain because of their high content of polyphenols and these include dark chocolate, red wine, chili peppers, and certain spices, herbs, and teas (9).  Of all the herbs oregano has by far the strongest effect on reducing inflammation with turmeric and saffron being quite helpful too. To find out how strongly any herb or spice reduces inflammation you can go on the Internet and check its ORAC score, which stands for oxygen radical absorption capacity (9).

Spices like cinnamon and ginger also reduce inflammation. Lastly foods high in iron and magnesium promote good brain health and reduce inflammation. Oysters have lots of B12, zinc, and iron. Avocados have lots of magnesium. For those who can stand liver, beef liver, calf liver, chicken liver and French pate (chicken or pork liver with a dash of cognac) are excellent sources of iron but must be consumed in moderation due to high levels of Vitamin A which can be toxic when too concentrated (14). 

So, what are the worst foods most likely to cause brain inflammation by killing off good gut bacteria or causing direct damage to brain cells through oxidative stress? Among the worst are any foods with a high content of sugar or added sugar and foods that are rapidly converted to glucose in the blood, i.e., those considered high on the glycemic index (9). Why? The brain lives on glucose and is highly efficient at using it. The brain needs only 62 grams of glucose a day (9). One can of soda has 45 grams of sugar. Whether you drink a few sodas a day; consume candy, cookies or cake; or consume refined white flour products like white bread or pasta, you will flood your brain with glucose (9). This not only causes inflammation and depression, but it also reduces the supply of a key hormone in the brain called BDNF (brain derived neurotrophic growth factor). BDNF is required for neurogenesis, synaptic thickening, and neuroplasticity (9) which are crucial, because the more BDNF you have in your brain the better your cognitive functioning and the more resilient you are to stress (9). 

Although it is never a good idea to eat lots of sugar or lots of foods high on the glycemic index (those with sugar in rapidly absorbable form), there are foods you can consume that actually slow the absorption of sugar into your bloodstream. These include green tea, okra, sesame seeds, pumpkin seeds old-fashioned oats, and whole grains like quinoa, barley, buckwheat, and spelt (9). If you hunger for pancakes on the weekend, try making them with wholegrains and buttermilk (a probiotic); fry them in canola oil; top them with fresh fruits like bananas or blueberries; and sweeten them with natural maple syrup not the artificial stuff which is loaded with high fructose corn syrup, corn syrup, and chemicals that you need a PhD to pronounce. Ironically real maple syrup is so rich in minerals and antioxidants, it is comparable to the inflammation fighting properties of green tea (15), except that it is high in natural sugar and should be consumed in moderation 

Other foods that are harmful to the brain and big contributors to inflammation are fried foods because they kill off good gut bacteria. The main culprits are fried fish, fried chicken, French fries, chicken fried steak, samosas, and empanadas (9). To really go off the deep end how about fried cheese sticks dipped in Ranch dressing or deep fried Twinkies, candy bars, burritos or pizza? Most bottled Ranch dressings are loaded with bad fats, sodium, and sugar (16).

Dr. Naidoo and others are clearly convinced that food and mood are so strongly related as to justify nutritional therapy for depression. Are there credible scientific studies that show consuming healthy food reduces brain inflammation and depression while eating junk food increases them? Although proof of causation is elusive, existing research shows a very compelling association between food and mood. 

Irene Lazarevich and colleagues analyzed the mood and eating patterns of 1,104 male and female college students and concluded that the students who ate the most fried foods, sweetened drinks, and sugary foods had a significantly higher rate of depression (17). A study of 37,131 people showed that those who drank 2.5 cans of soda a day had a 25% greater chance of developing depression than non-soda drinkers (18). In her systematic review of six studies Stephanie Cheung and colleagues found that depressed patients had significantly fewer populations of healthy gut bacteria and significantly higher populations of gut bacteria known to cause inflammation (19). 

Michael Messaoudi and colleagues randomly assigned 55 healthy men and women to receive either a daily probiotic or a placebo over a one-month period. Pre and post study mood questionnaires and urine samples showed the probiotic group reported less depression and had lower cortisol levels (20). Alban Gaultier and colleagues observed that stressing rats caused a drop in their gut population of Lactobacillus with onset of depressive behavior, and that administration of live Lactobacillus reversed the depression (21). His work has been confirmed by others including Yiquan Yang and Ioana Marin. 

So, what are the lessons here. First, food can either cause or mitigate depression by increasing or decreasing good gut bacteria and brain inflammation. Second, when clients are depressed, they suffer from brain fog, decreased cognitive and executive function, and decreased will power. They also seek comfort. Thus, they are prone to eat the worst kinds of foods like soda, ice cream loaded with cookies or candies, cake, chips, nachos, cheeseburgers, mac-n-cheese, pepperoni and sausage pizza, and fried foods. This serves to prolong and deepen their depression. Instead of making them feel better they feel worse - like they have swallowed a proverbial gut-bomb and paid for their bad eating with more intense depression. If eating poorly has been a long term habit that has contributed to chronic depression, now is the time to start eating healthy and reap the  rewards in terms of improved health and mood.



1  Agency for Healthcare Research and Quality Effective Healthcare Program. Depression Treatment after Unsatisfactory Response to SSRIs When Used as a First-line Therapy. 6/15/10

2 Comparative Effectiveness Review (number 7). Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. (2007)

3 Hall, H. Antidepressants and Effect Size. Science-Based Medicine. 7/19/11

4  Study by Dr. Jeffrey Meyer and colleagues at the Centre for Addiction and Mental Health in Toronto, Canada, published 1/28/15 in JAMA Psychiatry. 

5 Orsini, L. et al. C-Reactive Protein as a Biomarker for Major Depressive Disorder? Int. J. Mol Sci. 2022 Jan 30; 23(3) 1616. 

6 Pitharouli, MC et al. Elevated C-Reactive Protein in Patients with Depression, Independent of Genetic, Health, and Psychosocial Factors: Results From the UK Biobank. Am J Psychiatry. 2021 Jun; 178(6) 522-529

7 Science Friday talk by Dr. David Hellerstein. Depression Isn’t Caused by Low Serotonin. So How Do Antidepressants Work? 1/16/22 

8 Adan, RAH et al. Nutritional psychiatry:  Towards improving mental health by what you eat. European Neuropsychopharmacology Dec 2019; 29(12) 1321

9 Naidoo, U. This Is Your Brain On Food. Chapter One. (Little Brown Spark, New York, 2020)

10 Porges, SW. The Pocket Guide to The Polyvagal Theory: The Transformative Power of Feeling Safe. Norton Professional Books, New York 2011

11  Mitchell, L and Stewart, C. The important role of serotonin in your gut. Aug 2020

12 Colasanto, M. et al. Depression and inflammation among children and adolescents: A metanalysis. J Affect Disorders. 2020 Dec 1; 277: 940-948

13 Sapolsky, RM Why Zebras Don’t Get Ulcers. Chapter One (Holt Paperbacks, New York, 3rd ed.)

14 Peters, B. What is Vitamin Toxicity? 3/22/20

15. Maxwell, CA. Maple Syrup: A Sweet Superfood? Ask Dr. Maxwell Feb. 2018. 

16 Braverman, J. Is Ranch Dressing Healthy? Livestrong. 12/9/19

17 Lazarevich, I et al. Depression and food consumption in Mexican college students. Nutr Hosp. 2018 May 10; 35(3) 620-626

19 Cheung, S. et al. Systematic Review of Gut Microbiota and Major Depression. Frontiers of Psychiatry, 11 Feb 2019

20 Messaoudi, M. et al. Assessment of psychotropic-like properties of a probiotic formation in rats and human subjects. British Journal of Nutrition. 2010: 105(5): 775-64

21 Gaultier, A et al. Microbiota alteration is associated with the development of stress-induced despair behavior. Scientific Reports. 07 March 2017. 

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