How Diet Can Have A Positive Effect In the Management of Depression?

The gut microbiome- the community of bacteria and their genetic substitutions residing in the gut- sometimes referred to as a virtual organ interacts with the environmental risk factors such as stress and diet which suggests the pathophysiological role of microbiota in several disorders from atopy to depression. New insights into human health studies target gut microbiota for the treatment and prevention of depression and other mental health disorders. In this article, we will study the evidence-based relation of the diet with the depression through the linkage of the diet-gut microbiome-brain axis. Further, it will highlight the possible treatments for depressive orders arising from this evidence.^[1]

The human intestine is a home for nearly 100 trillion bacteria which helps in digestion of ingested polysaccharides from the diet. The gut microbiota, therefore, is critical for the development of a perfect immune system of the human body. Recent studies investigate the bidirectional communication between the gut and brain. The relation of gut microbiota to the brain involves the autonomic nervous system (ANS), enteric nervous system (ENS), neuroendocrine system and immune system in the communication path.^[2]

Clinically, depression is associated with the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and therefore, treatment of the disorder involves normalization of the HPA axis. The gut microbiota plays an eminent role in the early life programming of the HPA axis and postnatal development of the stress response system. The stress response system is immature at the time of birth and develops over the lifespan, hence, coincides with the intestinal bacterial colonization. Whenever stress is developed in the body, the permeability of intestinal bacteria towards immune cells and neuronal cells of ENS increases. The translocation of microbiota in the presence of stress defines the bidirectional communication of microbiota with the brain via the immune system and ENS.^[2]

Depression is a condition of changing from pleasant to an unpleasant one. In adolescents and children, this change of mood is called irritability. When the mood swings rise every day and it starts affecting the performance of day to day activities, depression takes place. The marked example of this is the loss of interest or pleasure in usual activities. Depression or anhedonia is also associated with loss of self-recognition, impaired concentration, and attention. List of dietary supplements involved with the management of depression includes:

Several research studies associate depression with the dietary intake of nutrients. The most studied ones are omega-3 (n-3) and folate/folic acid. Depressed adolescents or children are generally found low on these nutrients while supplementation improves their condition.

The relation of fatty acids, especially omega-3 polyunsaturated fatty acids (PUFA) to the depression in adolescents was found by Peet et al. (1998). His research showing declined concentrations of omega-3 PUFA and docosahexaenoic acid (DHA) in the red blood cells (RBC) in the depressed patients elaborated on the RBC membranes as a measure of omega-3 fatty acid composition in the brain. Increased levels of omega-3 fatty acids lead to enhanced membrane fluidity, in result, transportation of serotonin is increased into the endothelial cells. Hence, the explanation for depressed patients showing reduced serotonin uptake is clear.^[3]

Depressed patients report lower blood concentrations of vitamin B12 (approximately 258pmol/l) when compared with healthy individuals. Folic acid and vitamin B12 are involved in the synthesis and metabolism of serotonin, hence, required for normal central nervous system functioning. Folate or vitamin B12 deficiency can cause an elevation in homocysteine levels which can cause toxicity in neuronal cells. Hence, making the condition for depressed patients more worse. Also, lower selenium intakes, i.e., in the range of 13 µg/day, can also be related to the depression. The metabolism of selenium is different in the brain when compared with other organs and therefore, could disturb brain function. Also, selenium is required for the synthesis and metabolism of thyroid hormones and in turn, thyroid function can be associated with the symptoms of depression. Decreased plasma zinc levels also show the association with the depression.^[3]

Eicosapentaenoic fatty acid (EFA): Omega-3 fatty acids and folic acid supplementation can yield therapeutic effects even in individuals who are not responding to the standard antidepressant medications. A double-blind, placebo-controlled pilot study of 20 children of 6-12 years of age group was used to confirm these results. The participants were divided randomly into two groups, the first omega-3 fatty acids treatment group, and another placebo. Seven of the ten children from the treatment group showed improvement on a scale of more than 50% as per their self-assessments. While the statistics were zero in the placebo group. To deliver this fatty acid, eicosapentaenoic acid (EPA) supplementation is used. The latter is responsible for reducing psychopathic, aggressive, and impulsive behaviors in a very short duration.

Folic acid: Multivitamin, minerals and EFA supplementation in 231 adult prisoners over two weeks to nine months reduced up to 35.1% of their disciplinary offenses. For vitamin supplementation, folic acid has shown promising antidepressant effects. Along with antidepressant therapy, 500µg/day administration of folic acid can show significant improvements. The responses measured on the Hamilton Rating Scale of depressive symptoms can be characterized as significant if the score is below 50%.

Vitamin B6: It plays an eminent role for pre-menopausal women suffering from depression.

Thiamin: National Diet and Nutrition Survey (NDNS) recommends 0.63-2.66 mg of thiamin every day can significantly improve behavioral symptoms especially in female adolescents.

Zinc: NDNS recommends zinc supplementation in the range of 4.9-19.6 mg/day in males and 3.3-17.3 mg/day in females to augment the antidepressant therapy.

Chromium: A 600µg/day of chromium supplementation can be very effective, but UK adults are found to consume only 246-343µg/day of chromium.^[3]

Nutrients proved to be beneficial in the management of depression and other mental disorders can work via three possible mechanisms:

• First, re-correcting the nutrient inadequacies arose from a long-standing poor diet due to loss of appetite or personal care during depressive episodes.
• Second, any medical issues (due to depression) affecting the nutrients absorption, transportation, or storage. Therapeutic dietary doses of the nutrients can match up the raised nutritional demand.
• Third, it augments the efficacy of antidepressant medications. Omega-3 fatty acids and folic acid are beneficial for the treatment in resistant cases.^[3]

Obesity in the US population is closely associated with mood and anxiety disorders. Obesity in adolescents can be a reason for depression in their life later while depression in childhood can become the reason for adult obesity. The National Institute for Clinical Excellence (NICE, 2005) has also listed obesity as a risk factor for depression. The dietary changes which can affect body weight ultimately help in dealing with depression or other mind related issues.

During depressive episodes, some subjects overeat carbohydrate-rich food which shows the therapeutic effect in their condition due to increased brain serotonin levels. More the consumption of carbohydrates, more is the release of serotonin from brain neurons, ultimately boosting the moods. Unfortunately, this self-medication of overeating will result in weight gain and hence, become the reason for body dissatisfaction in adolescents. And body dissatisfaction is one of the prominent symptoms of depression. Following the concern of body image, the patient will go on intentional dieting for weight loss. The food which was once the reason for mood elevation is not being consumed by the patient and chances of severe depression become more.^[3]

Depression can be controlled by following a specific lifestyle involving the adoption of a Mediterranean diet, regular moderate physical activity and exposure to sunlight (natural light treatment) in the seasonal phase of depression. When any one of the modifications is carried out, it will bring the indirect change in other factors. A study was conducted to determine the efficacy of three combined recommendations, i.e., exposure to sunlight, exercise and vitamin pills in a sample of women who are not undergoing any antidepressant treatment. Following the results, another study was conducted using light therapy and exercise in subjects. Finally, another study using sleep deprivation and light therapy was conducted in bipolar patients. All of these studies reported positive results. To sum up the conclusion, the combined four recommendations, i.e., sleep, exercise, diet and sunlight exposure were used in the following study:

Method: Eighty patients, aged 18 or more, with a depressive episode were recruited for the study. All the subjects were on antidepressant treatment. Subjects suffering from any disease which may affect the CNS or undergoing hallucinations or suicidal thoughts at the time of study or pregnant women were excluded from the study.

The subjects were enrolled in two groups, the first active treatment group and another control group, randomly. Active treatment group subjects were educated with the four hygienic-dietary recommendations. The control group was told to follow the eating, sleeping, exercise, and exposure to sunlight as they feel better to do.

Active Group Intervention: The four recommendations used for the active group treatment includes:

• Go to bed when sleepy and never before 11:00 pm. Do not read, watch tv or perform any other activity lying on the bed. If do not fall asleep within 15 or 20 minutes, leave the bed and let yourself involved in activities until it gets sleepy. Do not wake up later than 9:00 am. Do not nap during the day, no matter how well you have slept the night before.
• Walk at least one hour a day at a pace that does not shorten your breath or makes you uncomfortable. Take a quick shower after exercise.
• Expose yourself to sunlight for a minimum of two hours a day keeping precautions for sunburn or sunstroke in hand.
• Adopt a healthy and balanced diet. Fix your eating hours and avoid consuming sweets. Take fish at least three times a week. Add more fruits, cereals, nuts, and vegetables in your diet.

Outcome Measures: Hamilton Depression 17-item scale was used to measure the primary outcomes of the treatment. Structured Interview MINI, Beck Depression Inventory 21-item, and Clinical Global Impression scale were also used. The results were measured at a gap of six months as per protocols.

Statistical Analysis: Statistical Package for the Social Sciences (SPSS) version 17 was used for data analysis. ANOVA (Analysis of variance), Mann-Whitney, Chi-square and Fisher’s exact test were also used to interpret the data.

Results: All scales determined a significant improvement in the symptoms of the active treatment groups. No unwanted side effects were reported from the adoption of recommended lifestyle modifications. A significant number of subjects from the active treatment group reported a 50% reduction in the HAM-D scores when compared to baseline scores. However, the prescription of antidepressant medications increased in nine subjects of the active treatment group but the count was seventeen in the control group. Also, the reduction in the use of these medications occurred in eight patients from the active treatment group while the count was only three in the control group (p=0.03).

Discussion: The increased prevalence of depression in Western countries can be related to their lifestyle. The majority of the population has reduced their physical activity and adopted an unbalanced diet. Sleeping hours have become less for them and exposure to sunlight has reduced significantly. The mechanism behind the therapeutic effects of these recommended modifications is very complex but involves changes on biological, psychological and social levels. Exercise maintains the balance of serotonergic, dopaminergic and noradrenergic systems, therefore, reduces stress. The Mediterranean diet can alter brain monoamine levels and brain-derived neurotrophic factor (BDNF). Exposure to sunlight and maintained sleep cycle are capable of modifying brain neurochemistry, i.e., cortisol secretion, thyroid-stimulating hormone, melatonin, and monoamines, hence, manages depression.^[4]

The indirect relation of the diet with the depression can be defined with the persistent role of gut microbiota in it. The hypothalamus-pituitary-adrenal axis is associated with the management of depression in patients. The gut microbiota is involved in the early life development of the HPA axis. In the stress episodes, the permeability of intestinal bacteria towards immune cells and neuronal cells of ENS increases. This explains the bidirectional communication of microbiota with the brain involving the immune system and the enteric nervous system (ENS) in it. The balanced Mediterranean diet, sleep cycle, moderate regular exercise, and sunlight exposure are effectively beneficial in the management of depression. The lack of adoption of these four basic recommendations has increased the prevalence of depression in Western countries. The balanced diet should include recommended consumption of omega-3 fatty acids, vitamins, and minerals for the desirable results. Eicosapentaenoic fatty acid (EFA), folic acid, vitamin B6, thiamin, zinc, chromium are important parts of a healthy diet. Other than the diet, obesity can also be indirectly related to depression. The destructed body image creates dissatisfaction. Here also diet and basic lifestyle modifications can help in overcoming this dissatisfaction. Hence, diet therapy along with a few changes in lifestyle can effectively manage the depression in patients following antidepressant medications.

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