Functional Medicine
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Nutrition and microbiome: factors for mental health

by Dr. Lawrence Cheng, MD and Dr. Ashley Riskin, MD

matrix of nutritional foods

Our health, including our mental well-being, is the result of a multitude of factors, including the complex interactions between our unique genes and the environment. How environment influences gene translation is called epigenetics.

In epigenics, it is known that many components of diet can profoundly affect our biochemistry by how our genes are translated (nutrigenomics). 

Healthy food intake is linked to mental well-being. There is increasing evidence for deficiency of both macro and micronutrients being linked to mental health disorders. 

In addition, we are learning about the strong connections between gut health, microbiome balance and mental well-being. 

In treating patients, laboratory testing for key nutrient elements, as well as gut digestive function and microbiome balance, may be helpful for targeted lifestyle interventions. 

Nutritional factors and mental health

A variety of dietary factors influence our mental health over our lifespan. These can include:

  • Processed, refined and poor-quality foods
  • Gut dysbiosis
  • Blood sugar and metabolic dysregulation
  • Inflammatory foods
  • Vitamins and mineral deficiencies

Blood sugar 

Elevated blood sugar and dysregulated glucose control can be associated with risk of depression and mood disorders.

We know that increased blood sugars can start a cascade of proinflammatory processes that can lead to changes in mental health by increasing gut and brain inflammation.

Inflammation and insulin resistance in the brain can impact neurotransmitter function and lead to low mood or depression in subjects.


Minerals have an important role as co-factors in metabolic pathways including those involved with neurotransmitter production.


Iron deficiency can have an adverse impact on the developing human brain and can increase risk for depression, anxiety, ADHD and other mental health conditions. Low iron may impact neurotransmitter production such as serotonin, dopamine and norepinephrine


The second most abundant trace mineral after iron, zinc is present in high amounts in the brain areas most associated with emotional processing including the hippocampus and frontal cortex. 

Low zinc levels can adversely impact mood. Improving zinc levels may improve mood by increasing brain plasticity, balancing excitatory and inhibitory neurotransmission and reducing inflammatory cytokines. 


Known as the ‘calming mineral’, magnesium can lesson anxiety and improve mood. This mineral is involved in hundreds of metabolic pathways in the human body and supplementation can reduce anxiety, stress and mild-to-moderate depression. 

Magnesium is a co-factor for creating enzymes that degrade norepinephrine and epinephrine and can therefore help calm over excitement in the brain.


Some vitamins have been identified as contributing to mental health.


A member of the B vitamin family, we see that impaired folate metabolism can impair mental health. We now test for the MTHFR gene which is associated with one aspect of folate activity. Certain gene variants are linked to depression, anxiety, ADHD and other mental health disorders. 

It may be worth looking at markers of this pathway and supplementing accordingly (via vitamins or whole foods). 

Vitamin B12 

This vitamin is involved with folate and the homocysteine pathways and play a role in neurotransmission. Low B12 levels have been associated with cognitive decline, irritability, depression and even psychosis. By age 45-50, our ability to absorb B12 declines, and it may be worth considering supplementation. 

Vitamin B6 

A crucial co-factor in the synthesis of serotonin, dopamine and epinephrine, B6 deficiency can sometimes be linked to depression and anxiety.


Choline is a crucial nutrient in brain development and is an important factor to consider in pregnancy and fetal brain development. It may be worth considering for adults, in terms of improving mood and lowering anxiety. 

Vitamin D 

Data is emerging that Vitamin D is associated with mental health and that supplementation may improve depressive symptoms. In our Canadian climate, it is believed that most of the population cannot achieve adequate levels without supplementation year-round. 

Essential fatty acids 

The Omega-3 fatty acids (EPA and DHA) demonstrate multiple mental health benefits. Critical for brain development, these essential fatty acids are important for mental health and supplementation can act to reduce depressive symptoms and regulate the nervous system. 

These essential oils may act to alleviate neuroinflammation and have an effect in maintaining neuronal cell membrane fluidity and function.

Laboratory nutrient testing for nutrients 

Nutrient levels including key vitamins, minerals, fatty acids can be measured through lab testing. 

The gut-brain axis 

The connection between nutrition and mental health is mediated largely through the gut-brain axis.  

The gut-brain axis is the bidirectional signaling pathway linking the nervous system of the gut, the enteric nervous system, the gut microbiome and the central nervous system.  

Messages are transmitted between the gut and the brain via neurotransmitters, stress hormones, inflammatory mediators, gut microbial metabolites and the vagus nerve. 

There is increasing evidence to suggest that factors disrupting the intestinal barrier and balance of the gut microbiome, especially early in life, may increase the risk of mental illness including the commonly seen anxiety and depression that are so prevalent in society today. 

Connection: gut inflammation and mental health 

There are many factors that influence and modulate our microbiome. These include mode of birth, breast-feeding and/or formula, antibiotic exposures, diet, toxins and stress. 

Although we can’t do much about our mode of birth,  there are still many modifiable factors—most notably our diet. There are a number of studies that have shown that an anti-inflammatory diet (Mediterranean style) can reduce markers of inflammation. Various mental health conditions including mood disorders have been linked to heightened systemic inflammation. 

One of the mechanisms by which food affects inflammation may be mediated by its effects on the gut microbiome. Diet is a potentially modifiable determinant of diversity, relative abundance and functionality of the gut microbiome.  

In addition, low grade systemic inflammation may be a result of a compromise of the gut mucous layer allowing increased permeability (“leaky gut”).  

Consuming the right types of probiotics, prebiotics and fermented foods may confer a benefit for mental health.  Probiotic species that may have beneficial effects on brain and mental health function are being called ‘psychobiotics’. Microbiome testing may help direct probiotic recommendations. 

Microbial metabolites impact mental health and behaviour 

Gut microbes produce an array of metabolites that send messages to the brain. These can affect cognition, emotional well-being and behaviour. Imbalances in the microbiome can be encountered due to a pro-inflammatory diet, antibiotics, stress and lifestyle factors. This can result in aberrant microbial signaling and may contribute to mental health disorders such as anxiety, depression, bipolar disorder, and schizophrenia. 

Several types of gut bacteria produce neurotransmitters identical to our own including GABA, which is typically associated with a more calming effect. The lactobacilli family contains of a number of species that produce GABA and serotonin but are susceptible to depletion by antibiotics and a high sugar/fat inflammatory western diet. 

Other microbial metabolites, including short chain acids (butyrate, propionic acid), bile acids, vitamins (B12, biotin), interact with our brain to modulate emotional behaviour via vagus nerve and direct stimulation of immune system. 

Functional medicine testing for digestive and microbiome imbalances 

Functional medicine testing, including comprehensive digestive/stool analysis, may be helpful in identifying imbalances in the gut microbiome, signs of increased gut permeability, gut mucosal inflammation, digestive dysfunction, gut immune system response as well as pathogenic bacteria, parasites and more. This testing may be helpful to  direct more targeted lifestyle interventions including diet, supplements, probiotics and botanicals. 


Dr. Lawrence Cheng, MD, CCFP(EM), MPH, is clinical co-director and co-founder of Connect Health Centre.

Dr. Ashley Riskin, MD, is clinical co-director and 
co-founder of Connect Health Centre.