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Depression and the role of inflammation

Depression affects more than 168 million people worldwide. Depression is also one of the key factors for impaired quality of life in patients affected by chronic diseases [1]. New research suggests that depression and inflammation are biologically linked ― a finding that may have important implications for patients whose condition fails to respond to treatment with antidepressants [1]. In a large examination of genetic, environmental, lifestyle, and medical drivers of inflammation in major depressive disorder (MDD), levels of the key inflammation marker C-reactive protein (CRP) were higher in patients with depression than in those with no mental disorder [2]. It seems that the activation of depression and inflammation is also connected to other stress responses.

Inflammation and depression:

Inflammation is an immune response to infection or other stresses on the body. High inflammation levels are associated with autoimmune disorders and can be risk factors for cardiovascular illness or other ailments [1]. 

Pariante, professor of biological psychiatry at the Institute of Psychiatry, Psychology, and Neuroscience, Kings College London says that the immune factors that are circulating can cross the blood-brain barrier and perpetuate depressive symptoms by changing the function of the brain areas responsible for the interpretation of emotions. 

This results in a negative feedback loop in which inflammation makes the body believe it is under threat, produces a more robust immune response, and perpetuates or exacerbates depressive symptoms [1]. Inflammation also dampens the effectiveness of antidepressants by reducing the brain's production of mood-determining chemicals such as serotonin. 

The neurological after-effects experienced by some patients after covid-19 may also shed some light on the connection between inflammation and depression [3]. Scientists are still uncovering how the new coronavirus impacts the brain and the central nervous system, but they believe the infection could inhibit blood and oxygen flow to the brain and in some cases, trigger brain swelling. 

Diet and lifestyle:

Research on the effect of inflammation on depression sheds light on dietary and lifestyle habits that need to be reviewed. 

Overweight and more specifically the presence of visceral fat- the fat wrapped around our organs, leads to triggering inflammatory pathways in the body and signaling molecules that disrupt the body’s normal cause of hormonal actions. Visceral fat itself also becomes inflamed [4]. 

Your dietitian can help you to incorporate the following lifestyle interventions to combat inflammation and indirectly depression and mood:


  1. Chieh-Hsin L., Fabrizio F. The Role of Inflammation in Depression and Fatigue. Front Immunol. 2019;10:169.
  2. Pitharouli M.C., Hagenaars S.P., Glanvilee K.P., Coleman J.R.I., Hotopf M., Lewis C.M., Pariante C.M. Elevated C-Reactive Protein in Patients With Depression, Independent of Genetic, Health, and Psychosocial Factors: Results From the UK Biobank. American journal of psychiatry. 2021. Available from: https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.20060947
  3. Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, Melloni EMT, Furlan R, Ciceri F, Rovere-Querini P; COVID-19 BioB Outpatient Clinic Study group, Benedetti F. Anxiety, and depression in COVID-19 survivors: Role of inflammatory and clinical predictors. Brain behave Immun.2020;89,514-600.
  4. Item F., Konrad D. Visceral fat and metabolic inflammation: “The portal theory revisited” pt.2, Obesity reviews.2012;13:30 -39.

Celiac disease vs non-celiac gluten sensitivity

Celiac disease: is an immune-mediated disease in which people cannot eat gluten. If you have celiac disease, and you eat gluten, your immune system responds by damaging the small intestine. It results in the flattening of the finger-like villi in the small intestine resulting in maldigestion and malabsorption of nutrients.

Gluten is a protein found in wheat, rye, and barley.

Prevalence and onset and clinical manifestation:

In contrast to the dramatic classical presentation noted typically in younger children, many patients with celiac disease present at a later age with subtle symptoms, and the diagnosis of celiac disease may be delayed [1]. Onset and first occurrences of symptoms may appear any time from infancy to adulthood but the peak diagnoses accurse after forty [2]. The disease may become apparent when an infant begins eating gluten-containing cereals or only in adulthood when it may be triggered by surgery, stress, pregnancy, or a viral infection. 

The clinical manifestations of celiac disease that have been identified are extensive and varied and are no longer isolated to the gastrointestinal tract. Celiac disease has been associated with other autoimmune conditions such as autoimmune thyroid disease and type 1 diabetes [1]. 

Celiac disease manifestation can be asymptomatic (silent) to full-blown celiac disease [2]. Patients may present with a variety of symptoms ranging from fatigue, weight loss, diarrhoea, constipation, vitamin or mineral deficiencies, skin rashes, abdominal bloating or -pain, infertility, and miscarriage, joint pain, and stiffness. 

Gluten sensitivity or non-celiac gluten sensitivity is a term used to describe persons with nonspecific symptoms without intestinal damage [3]. It also refers to a state of increased immunological responsiveness due to exposure to the gliadin component in gluten in genetically susceptible people. Non-celiac gluten sensitivity can affect many organ systems such as the brain and nervous system.

A study by Harvard’s, Dr. Fasano published in 2015 explained that gliadin also triggers the production of another protein called zonulin which breaks down the gut lining and increases permeability. Substances leak from the gut into the bloodstream and incite inflammation. Fasano’s study concluded: “Gliadin exposure induces an increase in intestinal permeability in all individuals, regardless of whether or not they have celiac disease” [4]. Gluten sensitivity also increases the production of inflammatory cytokines, and these cytokines are pivotal players in neurodegenerative diseases. 

Dietary implications:

Lifelong adherence to a strict gluten-free diet is the only known treatment for celiac disease. If adhering to the diet the intestinal mucosa usually reverts to normal or near normal. Clinical symptoms can improve in 2 to 8 weeks of starting the gluten-free diet. 

All wheat, rye, barley, spelt, semolina, and bulgar should be excluded from the diet. Lactose and fructose intolerances sometimes occur secondary to celiac disease and sugar alcohols are not well absorbed [4]. Patients need to read labels of food for hidden gluten in bakery products and packaged food. A registered dietitian will be able to support a newly diagnosed patient in making healthy food choices, avoiding gluten and gluten-containing products, and monitor possible nutrient deficiencies. 

If consistent non-specific symptoms with underlying inflammation occur (and celiac is excluded) it is worthwhile to look into the possibility of non-celiac gluten sensitivity. A six-week trial excluding all gluten is suggested with guidance from a dietitian. 


  1. Barker JM, Liu E. Celiac disease: Pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr. 2008;55:349-346.
  2. Holtmeier W, Caspary WF. Celiac disease. Orphanet journal of rare diseases. 2006;1:3.
  3. Mahan LK, Raymond JL. Krause’s food, and the nutrition care process. 14th ed. St Louis, Missouri: Elsevier; 2017.
  4. Hollen J. et al. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015;7(3):1565-1576.

Low carbohydrate, healthy fat diet and other important nutrients for brain health


The size of our brain in comparison to the rest of our body is an important feature distinguishing us from other mammals. Our brain makes up 1/40 of our total body weight. The human brain also consumes gram for gram a huge amount of energy. It represents 2.5 percent of our total body weight and consumes 22 percent of our body’s energy expenditure at rest [1]. 

Research concerning brain health tends to focus on neurogenesis (forming of new neurons) and inflammation, and the role thereof in brain and memory decline with age.
Nutrition and the role that nutrients can play on the health, renewal, and sustaining of the brain is therefore an important aspect of health and lifestyle. 


A diet low in carbohydrates and high in healthy fats stimulate the brain to turn to fat for fuel in the form of ketones (a similar reaction that the brain has to fasting) [2]. 

Eating carbohydrates stimulates insulin production, which leads to fat production, fat retention, and a reduced ability to burn fat. As we consume carbohydrates, we stimulate an enzyme called lipoprotein lipase that tends to drive fats into the cells [3]. 

Healthy brain cells thrive when fueled by ketones and have positive effects on memory, visual attention, and task switching. The mechanisms of how the ketones can be helpful for the brain include reduced inflammation, more efficient energy production, and increased production of antioxidants [4]. Lower intake of carbohydrates also prevents insulin resistance in the brain which leads to inflammation in the brain. 

Other nutrients and brain foods: 

B Vitamins: 

The B vitamins, notably Vitamin B12, Folate, and B6, play an important role in controlling the body’s homocysteine levels. Homocysteine is a type of amino acid which the body naturally makes. High levels of homocysteine are responsible for damage to the artery linings and therefor affect the health of the brain. This may raise your risk for coronary artery disease, heart attacks, blood clots, and strokes. 

Vitamin D: 

Vitamin D is actually not a vitamin but a fat-soluble steroid hormone. Concerning the brain, it has the function of protecting neurons from the damaging effects of free radicals and reduces inflammation. Low vitamin D levels increase your risk for dementia and Alzheimer’s disease. Low vitamin D levels can also contribute to depression.[5] 

Omega 3 fatty acids: 

These fatty acids (EPA and DHA) are vital for the maintenance of normal brain function throughout life. They are abundant in the cell membranes of brain cells, preserving cell membrane health and facilitating communication between brain cells.[6] 

Coconut oil or MCT oils: 

MCT oils are a superfood for the brain with the added benefits of reducing inflammation.
When you’re on a low carb/ketogenic diet, MCTs can also be converted into ketones in the liver providing the benefits of ketones for the brain. 


Turmeric is a member of the ginger family and the seasoning that gives curry powder its yellow colour. Studies have shown that people who take in turmeric scored better on tests designed to measure cognitive function.[7] 


Foods rich in probiotics- live microorganisms that support our intestinal bacteria- can influence brain behavior and help alleviate stress, anxiety, and depression. By supporting your gut microbiome with food such as yogurt, kefir, fermented foods, or a probiotic supplement, you support not only your gut but also the health of your brain. 


You can make lifestyle changes today to keep your brain healthy, vibrant, and sharp while substantially reducing your risk of brain function decline and disease in the future. Following a low carbohydrate and healthy fat meal plan will support your brain and vascular health. 


  1. Perlmutter D. Grain brain. 2019. p201. 
  2. Cahill GF, Veech Jr. Ketoacids? Good Medicine? Transactions of the American Clinical and Climatological Association.2003; 114:149-61. 
  3. Ferreira LD, Pulawa LK, Jensen DR, Eckel RH. Over expressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance. "Diabetes.2001;50(5):1064. 
  4. M. Ota, et al., Effect of a ketogenic meal on cognitive function in elderly adults: Potential for cognitive enhancement, Psychopharmacology (Berlin)2016. 233(21-22):3797-802. 
  5. Littlejohns T.J., et al. Vitamin D and risk of dementia and Alzheimer disease. Neurology.2014. 83(10):920-8. 
  6. Front. Aging Neurosci. 2015. https://doi.org/10.3389/fnagi.2015.00052 
  7. Ng TP, et al. Curry consumption and Cognitive function in the elderly. American Journal of Epidemiology.2006 Nov;164(9):898-906.
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