Depression, inflammation and what can be done about it!

In the UK 1 in 20 people are diagnosed with depression.  Major depression (MD) is ranked by the World Health Organisation (WHO) as the leading cause of disease burden among high-income countries.  WHO predict that depression will be the leading cause of disability by the end of 2020.  It is estimated that the global prevalence of depression is 12.7% for males and 21.7% for females suffering from depression over a lifetime.  Suicide is the second leading cause of death in 15-29 year olds (WHO, 2019).

Symptoms of depression usually include feelings of worthlessness, loss of energy and fatigue, poor concentration, thoughts of suicide, a disturbed sleep pattern, loss or increased appetite and weight and agitation (Fried, 2017). 

Depression can be a result of a number of factors, such as previous trauma, genetic susceptibility, tryptophan depletion amongst others.   The immune system and inflammation is an area that is increasingly being researched for its role in depression and is considered to be an area for therapeutic intervention. Here’s why an anti-inflammatory diet could be a prescribed therapy in the future.

The kynurenine pathway

We obtain tryptophan from our diet from foods such as spinach, eggs and poultry amongst several others.  Tryptophan converts to 5HTP and then to serotonin (our feel good hormone) and melatonin (our sleep hormone).  If the body is triggered to increase inflammation then tryptophan doesn’t metabolise to serotonin.  Instead tryptophan is metabolised down the kynurenine pathway, which results in less serotonin being produced, and quinolinic acid being produced instead, which has shown to have a neurotoxic effect and is involved in several psychiatric disorders (Pierozan et al,2018). 

Tryptophan is degraded to kynurenine by idoleamine 2,3 dioxygenase (IDO) or tryptophan dioxygenase (TDO) (Schwarz & Pellicciari, 2002).  IDO is activated by inflammatory cytokines interleukin-1, interleukin-6 and tumour-necrosis-factor (TNF) – these are measures of inflammation.  TDO is activated by cortisol (your stress hormone).  Stress and alterations in the immune system can hinder tryptophan metabolism to 5HTP and ultimately serotonin/melatonin production, causing symptoms associated with low serotonin levels (Dantzer et a, 2008) such as depression and anxiety.  These pro-inflammatory cytokines can access the central nervous system and interact with a cytokine network in the brain that is able to influence not only neurotransmitter metabolism, but also neuro-endocrince function, synaptic plasticity and neuro-circuits that regulate mood.  This neuro-inflammatory depression is often seen in patients with inflammatory related diseases such as rheumatoid arthritis, infectious diseases, autoimmune disorders and cardiovascular disease (D’Mello & Swain, 2016; Evans et al, 2005).  Research confirms elevated concentrations of inflammatory markers including pro-inflammatory cytokines in the blood of both medically ill and healthy patients with major depression (Dowlati et al, 2010, Miller et al, 2009).

We can see then, that to maintain mental health, keeping inflammation in check is significant.  Diet has proven to influence the inflammatory state, highlighting the potential of diet as a therapeutic tool in depression and disorders with an inflammatory basis (Uher et al, 2014; Miller & Raison, 2015).

Meta-analyses of 11 studies comprising of 101,950 participants, showed pro-inflammatory diets increase the likelihood of a depression diagnosis when compared to those on an anti-inflammatory diet (Tolkein et al, 2018).  It’s important to note that each study within these meta-analyses had differing dietary protocols for an anti-inflammatory diet.  Interestingly this study underlines the effectiveness of a personalised diet improving depressive symptoms in comparison to receiving social support over a 12-week period (Jacka et al, 2017). 

Students with mild to moderate stress were 3 times more likely to consume processed foods and less likely to consume fruit and vegetables compared to students who weren’t experiencing stress (Papier et al, 2014).  Indicating that adverse mental health can influence dietary choices encouraging pro-inflammatory patterns and avoiding anti-inflammatory foods causing an increase in inflammatory status.  This creates a viscous cycle between depression and an inflammatory diet where both feed each other.  Stress management techniques should be incorporated alongside a nutritional protocol (Hammen 2015).

Research demonstrates that consumption of wholegrains correlate with lower inflammatory markers, whereas lower wholegrain intake has shown to increase inflammatory markers (Hajihashemi, 2014).  Choline, found in eggs, cauliflower and broccoli has shown to lower peripheral inflammatory levels, such as CRP, IL-6 and TNF-a (Detopoulou et al, 2008). 

Individuals with low blood levels of folate (B9), or high levels of homocysteine are more likely to suffer from depression, and less likely to receive a positive effect from anti-depressant drugs (Murakami et al, 2008).  When comparing the effects of an SSRI with placebo and with folic acid, 61% of patients improved on the placebo combinations and 93% improved with the addition of folic acid. 

A meta-analysis (Lin & Su, 2007), suggests that omega-3 fatty acids have significant anti-depressants effects in individuals with depression.  Evidence suggests EPA is the most potent anti-depressant (Martins, 2009).  Out of six double-blind placebo controlled trials, five showed a benefit of omega-3s for depression.  Omega-3 has shown to benefit patients who were on anti-depressants but still depressed, by the third week patients experienced improvements in their mood, whilst those on placebo hadn’t.

A correlation exists between uneven blood sugar levels and uneven mood. Poor blood sugar balance can be the predominant factor in mood disorders.  Symptoms of uneven blood sugar levels are synonymous with depression symptoms: poor concentration, fatigue, insomnia, irritability, and fluctuating moods.  Interestingly refined sugar and refined carbohydrates correlate with depression because these foods use up B vitamins to convert sugar into energy.  A study of 3,456 middle-aged civil servants who had a diet of processed foods, demonstrated a 58% increased risk for depression whereas those who described their diet as containing “more whole foods” had a 26% reduced risk for depression (Akbaraly et al, 2009). 

To conclude, inflammation and the stress hormone cortisol prevent serotonin from forming, increasing our risk of low serotonin symptoms seen in depression.  An anti-inflammatory diet may provide therapeutic effects in the way of depression.  Psychological interventions such as CBT and mindfulness should also be considered to ensure health positive decisions are made during times of low mood states and stress.


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