Diet And Depression: The Critical Link Between

Globally, more than 250 million people are affected by depression. Currently available treatment options can have substantial side effects and take weeks to be fully effective. Therefore, it is important to find safe alternatives, which act more rapidly and in a larger number of patients.

What Causes Depression?

There are several theories as to what causes depression:

The monoamine hypothesis is one of the best-known theories on the molecular origins of depressive: The underlying assumption is that a depletion of monoamines is responsible for depressive-symptoms. Monoamines such as norepinephrine (NE), serotonin (5-HT), and dopamine all play a crucial role in the coordination of mood, motivation, and circadian rhythms – processes, which are often affected during depression.
Growth factors are associated with depression as well. In particular, the brain-derived neurotrophic factor (BDNF) is strongly correlated with antidepressant action.
Another hypothesis implicates the hypothalamus- pituitary-adrenal (HPA) axis and specifically addresses the link between chronic stress and depression-risk. Through a hormonal cascade, stress increases the secretion of adrenal glucocorticoids. Glucocorticoids are involved in the control of neuronal survival, neurogenesis, synaptic plasticity and hippocampal size, linking brain function and stress.
Furthermore, there is evidence for a link between inflammation and depression. Analysis of peripheral blood from depressed-patients revealed elevated levels of inflammatory biomarkers, including cytokines, chemokines, and adhesion molecules. These molecules can cross the blood–brain barrier, where they interact with different brain regions involved in monoamine synthesis, neuroendocrine regulation, and neuronal plasticity, which are heavily implicated in depression. Since inflammation affects monoamines and the HPA axis, an interaction between many different factors is likely to contribute to depression.
Cellular damage due to excitotoxicity, changed gene expression, chronic stress (e.g., due to nitric oxide) or elevated inflammation in the brain can also be observed during aging. Symptoms that are associated with depression, including cognitive decline, fatigue, or sleep disturbances, often occur in aged populations, especially in the context of neurodegenerative diseases. Furthermore, depression patients have a shorter average life expectancy. This connection led to the hypothesis that depression is a condition of accelerated brain ageing.
Depression can be, at least in part, understood as a metabolic disorder. There is a bidirectional comorbidity between depression and obesity. Above-mentioned alterations in the HPA-axis and inflammation as well as genetics may be shared risk factors for both, depression and metabolic changes. However, more direct metabolic regulators may affect depression as well. For instance, the feeding hormone leptin has antidepressant-like effects in mouse models, while deletion of the leptin receptor in certain brain areas can induce resistance to common antidepressants. There may also be an association between insulin resistance and depression in patients.
The microbiome, which is critical in both, regulating nutrient uptake and fighting inflammation, appears to be affected in depressed patients as well.
Twin studies suggest that depression is only 37% heritable. Hence, there is a strong environmental component to this disorder.

It is not that one of these is correct and one of these is wrong – the condition is a multifaceted disease and there are going to be many underlying factors that may need to be considered. Hence the saying in Functional Medicine:

Treat the individual, not the disease.

What Nutrients Might Cause Depression?

While much research on depression focuses on chronic stress as a main risk factor, a recent review makes a point of exploring dietary factors as a somewhat overlooked, yet highly promising approach towards novel antidepressant pathways.

What Nutrients Are Associated With Depression?

Deficiencies in various groups of nutrients often occur in patients with mental disorders. These include vitamins, minerals and fatty acids, especially:

Members of the B-complex (B6, B9, B12).
An imbalance of fatty acids, such as omega-3 and omega-6
An insufficient supply with minerals, including magnesium and zinc.

Non-vital dietary factors may affect depressive symptoms as well. For instance, the most commonly consumed psychostimulant caffeine may improve behavioural and molecular markers of depression.

How Do Nutrients Help Depression?

While some of them are relevant for the synthesis of monoamines, others play a crucial role in inflammation, neuroprotection and the synthesis of growth factors.

Evidence suggests that when deficiencies return to normal, changes in mood and behavior can be, at least in some cases, achieved. Furthermore, supplementation with dietary factors (so called “nutraceuticals”) may improve depressive symptoms even in the absence of a deficiency.

Vitamin B6 And Depression

Pyridoxine, pyridoxal, and pyridoxamine are three related, naturally occurring isoforms that are grouped together under the name of vitamin B6. They can be obtained from a variety of food, including meat, dairy products, grains, nuts, vegetables, and certain fruits.

Vitamin B6 is involved in:

The serotonin pathway.
Kynurine pathway.
Regulates the immune system from stressors.

Vitamin B6 supplementation improved depressive-symptoms in an aged cohort and vitamin B6 levels generally correlated with depression severity. Furthermore, lower vitamin B6 intake correlated with disease severity in female depressed-patients. The diagnosis of vitamin B6 deficiency in depressed patients and the subsequent change in diet could therefore serve as a treatment complementary to drug therapy.

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Folate and Vitamin B12 And Depression

Folate and vitamin B12 are involved in many mechanisms that are impaired in depression. The synthesis of monoamines, the regulation of the immune response, chromatin modifications as well as the removal of metabolic by-products with neurotoxic effects are disrupted during vitamin B9/12 deficiencies. Both interact and influence one another. This, however, also results in studies that are often insufficiently distinguishing between the effects of each vitamin on its’ own.

Human studies on folate generally support its’ role in depression. For instance, a large meta-analysis shows that vitamin B9 deficiency is associated with higher depression risk, even after controlling for confounding factors. Folate deficiency also occurs more often in treatment- resistant patients and correcting this deficiency can aid in depression-treatment.

The link between vitamin B12 and major depressive disorder is even more evident.

Vitamin B12 deficiency leads to symptoms of depression, and can be diagnosed in up to one third of depressed patients. Accordingly, chronic supplementation with injected vitamin B12 improved depressive-symptoms in two large cohorts. Notably, chronic supplementation with either, folate or vitamin B12, may improve depressive-symptoms particularly in men.

Magnesium And Depression

Magnesium is an important modulator of various processes in the human body. It serves as a cofactor in over 300 different reactions, including DNA replication, transcription and translation.

Obtained from foods such as nuts, seeds, grains, and green leafy vegetables, magnesium+ is essential for healthy brain.

Zinc, Diet And Depression

The second most common trace element in the human body after magnesium is zinc. Although zinc can be obtained from plant foods including cereals and legumes, the absorption of the ion can be impaired by the phytic acid present in plants. The bioavailability of zinc from crops is therefore often limited. The main sources of zinc are thus red meat, oysters and crabs. Zinc is involved in countless enzymatic reactions, both systemically and in the brain. These include pathways that regulate biosynthesis, neurogenesis, antioxidant defense and the immune response.

There is a strong negative association between depression and zinc levels, which has led to the suggestion to use serum zinc levels as a biomarker for affective disorders

Omega 3, Diet And Depression

The organ with the highest proportion of fatty acids, besides adipose tissue itself, is the brain. Fatty acids are essential for the development and maintenance of the central nervous system, are involved in various biological processes within the brain and play an important role in the stability and structure of membranes. Of all lipids found in the brain, poly-unsaturated fatty acids (PUFAs) constitute the largest fraction. In this context, the so-called Omega-3 (ω3) and Omega-6 (ω6) PUFAs are of great importance.

Depression rates are generally higher in regions with low fish consumption, a main source of ω3 PUFAs.

Accordingly, supplementation with ω3 PUFAs may improve depressive-symptoms. ω3 PUFAs also appear to improve markers associated with depression in humans including the HPA axis and inflammatory markers

There is increasing consent that ω3 PUFA supplementation promotes positive outcomes for mental health problems including depression. Combined with other benefits such as a lower risk for cardiovascular disease, high ω3 PUFA content in the diet is likely to generally improve health in human populations. However, supplementation may have to be tailored to the type of depression as well as to the antidepressant treatment that is currently being taken by the patient.

Vitamin D And Depression

A systematic review and meta-analysis concluded:

low vitamin D concentration is associated with depression.

Caffeine And Depression

Caffeine appears to have several neuroprotective effects and may rapidly improve mood.

Human cross-sectional and prospective studies generally observed an inverse relationship between coffee intake and depression-risk. Given various other bioactive compounds in coffee other than caffeine, these studies are by nature not conclusive about caffeine effects alone. In fact research is clearly showing us that several of the other healthy compounds in coffee, such as chlorogenic acid may be beneficial in brain health.

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Conclusion: The Critical Link Between Diet And Depression

There is a lot to be explored within the area of lifestyle, diet and depression but the evidence to date is clear – diet plays a role in how we feel. This comes as not surprise to many of us! But please don’t ignore the many other factors which are equally important, and for some may be more important. Factors such as meaning and purpose in life, community, connection, time in nature, relationships, trauma, stress levels, our circadian rhythm (sleep), and physical activity levels. A holistic approach considering all these areas is essential when seeking optimal health.

References

The Way to a Human’s Brain Goes Through Their Stomach: Dietary Factors in Major Depressive Disorder: click here.
Nutritional aspects of depression: click here.
The Impact of Nutrition and Intestinal Microbiome on Elderly Depression-A Systematic Review: click here.
Dietary recommendations for the prevention of depression: click here.
Depressed gut? The microbiota-diet-inflammation trialogue in depression: click here.
Treatment of depression: time to consider folic acid and vitamin B12: click here.
The impact of whole-of-diet interventions on depression and anxiety: a systematic review of randomised controlled trials: click here.
Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials: click here.
Dietary magnesium intake and risk of depression: click here.
Seafood Consumption, Omega-3 Fatty Acids Intake, and Life-Time Prevalence of Depression in the PREDIMED-Plus Trial: click here.
Nutrition and depression: implications for improving mental health among childbearing-aged women: click here.
Association of total zinc, iron, copper and selenium intakes with depression in the US adults: click here.