Written by Dr. Sanjana V.B Bhms,dbrm,cdn

Founder & medical director of siahmsr wellness.in

All rights reserved with siahmsr digital healthcare[siahmsr wellness]

Reviewed by SIAHMSR medical team.

Role of supplements in reducing depression

Overview

Depression is one of the major mental health problems faced by people across the globe, due to genetic factors as well as environmental stressors such as challenges & conflicts of day to day life, surrounding us in an unprecedented way.

  The prevalence of depression is 8.7% in individuals aged between 18 and 25 years. Approximately, 264 million people worldwide suffer from this disorder. Depression is characterized by sadness, feelings of worthlessness or guilt, loss of appetite, sleeplessness,  loss of interest in activities or aimless physical activities or slowed movements, thinking challenges, and suicidal thoughts.

   Depression can reduce the activity levels and work efficiency of a person. It may limit the ability to focus on work or study. Depression has different grades or intensities and depression major, is the severe type which is associated with suicidal thoughts. Suicide is the worst impact of depression, causing the deaths of over 7 lakhs people every year. Suicide is the fourth leading cause of death among the adolescent and young population.

   Depression has different treatment modalities. Modern medicine as well as alternative /complementary medicine has various strategies or medicinal management options for depression. However, a few group of depressed individual do not prefer to take antidepressants as a long term treatment option. For them adjunctive therapies, such as dietary supplementation, can be tried.

  The most commonly used dietary supplements are omega fatty acids, vitamins and probiotics.

Research studies have showed that omega 3 poly unsaturated fatty acids PUFA (EPA eicosa pentaenoic acid and DHA docosa hexaenoic acid combination) are useful as supplements to reduce depression. Vitamin D, and probiotics also are common supplements used in reducing depressive symptoms.

   Depression has several types, including depressive disorder (clinical depression), bipolar disorder (manic depression), persistent depressive disorder (dysthymia), and seasonal affective disorder (SAD).

  Depression is closely linked to neurotransmitter substances of brain. Neurotransmitters that affect mood include dopamine, epinephrine, norepinephrine, GABA, and glutamate. Neuro transmitters are chemical messengers which help carry chemical signals from nerve cells to target cells. Each type of neurotransmitter lands on and binds to a specific receptor on the target cell.

The existence of complex interactions between neurotransmitters and receptors that affect the brain’s functions play a role in persistent depressive disorder.

GABA is the most common inhibitory neurotransmitter of the nervous system, particularly in the brain. It regulates brain activity to prevent problems such as anxiety, irritability, concentration, sleep, seizures and depression.

Serotonin is an inhibitory neurotransmitter. Serotonin helps regulate mood, sleep patterns, sexuality, anxiety, appetite and pain. Serotonin imbalance is associated with depression and a few other disorders

Dopamine helps with focus, concentration, memory, sleep, mood and motivation.

Role of dietary supplements in depression

Dietary supplements are orally consumed products, such as vitamins, herbs, minerals, amino acids, enzymes, metabolites, probiotics , polyunsaturated fatty acid (PUFA), vitamin D,18 B12,19 magnesium, zinc,20 and curcumin etc.

According to some studies [ see the references] supplements have a significant role in reducing depression.

In a review conducted by Hoffman et al, vitamin D and PUFA supplementation had complementarily positive effects on depressive symptoms, anxiety, and pain.

·      How do omega- 3 fatty acids PUFA help the brain to reduce depressive symptoms?

PUFA- poly unsaturated fatty acids or Omega  fatty acids.The most commonly used supplements in treating depression is the PUFA group, which is a combination of Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA).These are simply, omega 3 fatty acids.

Omega-3 fatty acids are substrates that help the formation of neurotransmitters and prostaglandins. Therefore, they have great role in the maintenance and regulation of a healthy brain. Furthermore, studies show that depression rates can increase with lowered levels of membrane-related omega-3 fatty acids.

They are linked to the inflammatory hypothesis of depression. According to this hypothesis depression is connected to the arachidonic acid inflammatory pathway. An elevated ratio of arachidonic acid to omega-3 fatty acid is associated with depression.

 The omega 3 fatty acids combine with arachidonic acid for amalgamation into membrane-based phospholipids, thereby reducing both cellular and plasma concentrations of arachidonic acid.

Prolonged systemic inflammation is linked to depression by some research studies ,although it needs further extensive research in future.

Polyunsaturated fatty acids (PUFAs) play a critical influence in the regulation of inflammatory signaling and potential vulnerability to depression [6].

 Studies show that omega 3 fatty acids ,particularly  DHA and EPA hinder the release of pro-inflammatory cytokines (interferon-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-2, and IL-6).

Therefore omega 3 fatty acids EPA,DHA combination supplements are used by health care providers as an adjunct dietary supplements.

·        Role of Vitamin D in managing depression 

Depression is reported to be the most common psychological problem in patients with chronic kidney disease (CKD). Several studies have reported that lower levels of serum vitamin D are significantly associated with depression. However, further extensive studies are  needed in this area.

One research has shown that vitamin D supplementation at 2000 IU/day–50,000 IU/week for eight weeks (two months) to 24 months of supplementation positively affected depression in these patients [2].

The lack of vitamin D in the serum can also lead to depression through mitochondrial function and serotonin formation pathways.

 In the serotonin formation pathway, vitamin D fails to induce the serotonin-synthesized gene of tryptophan hydroxylase 2 (TPH-2) while repressing the expression of TPH-1. Its consequence is reduced plasma tryptophan levels & tryptophan cannot be transferred into the brain. This inhibition results in low serotonin levels in the brain, causing depression.

Moreover, mitochondrial function will be impaired in the presence of low serum vitamin D levels, resulting in elevated reactive oxygen species (ROS).ROS are free radicals causing oxidative stress, which is very harmful to brain  and other cells of our body.

ROS can impact Ca2+ and antioxidant gene (GSH) homeostasis. Major  antioxidants in neurons are GSH or glutathione. glutathione is involved in disposal of peroxides by brain cells and protect against ROS. Glutathione is essential for cellular detoxification in brain cells.

Glutathione antioxidants are depleted when ROS is high, resulting in depression. Vitamin D protects against oxidative stress and consequent glutathione depletion and thus helps to reduce depression.

·      How do Probiotics help to reduce depressive symptoms?

  Probiotics are live microorganisms that can improve the gut health. Recently, they have been used to manage and treat various  types of diseases, including depression.

Lactobacillus (L. acidophilus, L. casei, L. fermentum, L.rhamnosus, and L. bulgaricus) and the genus Bifidobacterium (Bifidobacterium bifidum and Bifidobacterium lactis) are commonly included in probiotic supplements.

 One research study has explicated that probiotics can be used as adjunct therapies that can improve depressive symptoms in patients [3],[4].

 There is no clear cut evidence of probiotics treating depression successfully and more high-quality studies on patients with depression are still needed.

·      Multi-nutrients [vitamins& minerals] help to manage depression

Multiple micronutrients, such as vitamin B12, vitamin D, folates, zinc, and selenium, have been recommended for preventing depression in pregnant women & mothers. 

Some studies point out that the intake of multiple micronutrients and iron-folic acid groups had much impact in lowering depression scores during the first and second trimesters of pregnancy compared to folic acid alone.

Another study [5] reported that the consumption of supplements containing 12 vitamins, minerals, and herbs within eight weeks had significant results in decreasing depression.

Supplements also helped in reducing all the pro-inflammatory cytokines levels related to depression, such as IL-1β, IL-5, IL-6, TNF-α, and TNF-β.

Magnesium is proposed to be essential for improving synaptic functions, particularly in the hippocampal neurons of the brain.

Magnesium also influences the production of cyclic adenosine monophosphate response element-binding proteins that control genes related to brain function, particularly those involved in dopamine synthesis. Thus, magnesium can help alleviate depression.

·      Role of herbal supplements

Herbal ingredients (Ginseng and Ginkgo biloba), help to reduce depression through oxidative-stress reduction and mood enhancement.

·      Other supplementations that significantly reduced depression are the following:

 Carnitine , coenzyme Q10, nanocurcumin, curcumin, magnesium oxide, melatonin, myo-inositol, sumac (Rhus coriaria L.), vitamin A, vitamin B, folic acid, zinc, and zinc sulfate.

These supplements effectively protect brain cells and neurons from significant neurotoxic damage and lower pro-inflammatory cytokine levels (TNF-α and IL-1β), thereby reducing the overproduction of circulating TNF-α and IL-1β caused by lipopolysaccharides.

 oenzyme Q10, nanocurcumin, and curcumin also had neuroprotective properties, including antioxidant and anti-inflammatory activities.

References:

1.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123934/#:~:text=Other%20dietary%20supplementations%2C%20such%20as,on%20supplements%20for%20depression%20treatment.

2.    https://pubmed.ncbi.nlm.nih.gov/28192445/

3.    https://pubmed.ncbi.nlm.nih.gov/32528399/

4.    https://pubmed.ncbi.nlm.nih.gov/32009871/

5.    https://pubmed.ncbi.nlm.nih.gov/29929873/

6.    https://www.sciencedirect.com/science/article/abs/pii/S0889159112003947