Low mood: could a nutrient deficiency or hormone imbalance be the cause?

Vitamin D deficiency

Vitamin D receptors are found throughout the brain, concentrated in the hippocampus, prefrontal cortex, and amygdala, regions directly involved in mood regulation, emotional processing, and stress response. Vitamin D activates the gene encoding tryptophan hydroxylase 2, the enzyme that converts tryptophan into serotonin in the brain. When vitamin D is low, serotonin production may be reduced. This is a mechanistic pathway, not just a correlation. Large-scale observational studies consistently show that people with low serum vitamin D are significantly more likely to experience depressive symptoms, and multiple meta-analyses confirm that correcting a deficiency can meaningfully improve mood, particularly in people with confirmed low baseline levels. In the UK, where sunlight is sufficient for vitamin D synthesis only roughly from April to September, deficiency is extremely common, particularly in autumn and winter. Approximately one in five UK adults may have low vitamin D levels at any given time.

Vitamin B12 and folate deficiency

B12 and folate both sit at the centre of the methylation cycle, the biochemical process through which the brain synthesises serotonin, dopamine, and noradrenaline. When either is deficient, neurotransmitter production is impaired at the substrate level. B12 deficiency can present as low mood, emotional flatness, and irritability long before any neurological symptoms appear. Research shows that B12 deficiency can mimic depression closely enough that it is missed even in clinical assessments. Folate deficiency is similarly associated with depressive symptoms and with poorer response to antidepressant medication in people who are deficient. People who follow plant-based diets, take metformin or proton pump inhibitors, or have gut conditions affecting absorption are at particular risk.

Iron deficiency and low ferritin

Iron deficiency, even in the absence of anaemia, has a well-established relationship with mood. Iron is required for the synthesis of dopamine, serotonin, and noradrenaline, meaning that low iron stores directly affect the neurotransmitter systems most relevant to emotional wellbeing. Low ferritin also impairs oxygen delivery to the brain, contributing to fatigue and emotional blunting. Women with heavy periods and those following plant-based diets are among the groups most at risk of low ferritin without a diagnosis being made.

Thyroid dysfunction

Thyroid hormone drives the metabolic activity of every cell, including neurons. Low thyroid function (hypothyroidism) reduces neurotransmitter synthesis and metabolic rate in the brain, producing a cluster of symptoms that overlaps closely with depression: persistent low mood, fatigue, slow thinking, reduced motivation, and emotional flatness. Studies consistently find elevated rates of thyroid dysfunction in people presenting with depression, and it is estimated that a meaningful proportion of people diagnosed with depression have an unaddressed thyroid issue contributing. The overlap is large enough that a thorough thyroid panel, including Free T3 and thyroid antibodies, is a reasonable investigation for anyone with persistent low mood.

Blood sugar instability and metabolic health

Blood sugar that spikes and falls sharply produces mood changes that track the glucose curve: irritability, anxiety, and low energy in the troughs, temporary improvement after eating. Over time, higher HbA1c levels, even in the prediabetic range, are associated with increased risk of depressive symptoms. The mechanism involves both direct effects of glucose on brain function and indirect effects through systemic inflammation, which is elevated in metabolic dysfunction and independently associated with depression. Checking HbA1c and fasting glucose provides useful context for whether metabolic patterns are contributing to mood symptoms.

Systemic inflammation

Research over the past two decades has increasingly established that chronic low-grade inflammation plays a causal role in a subset of depression cases. Elevated CRP is found in a proportion of people with treatment-resistant depression. Inflammatory cytokines cross the blood-brain barrier and alter the metabolism of tryptophan, reducing serotonin availability and increasing the production of neurotoxic compounds. Homocysteine, which reflects B-vitamin metabolism and cardiovascular inflammatory risk, is also consistently elevated in people with depression. A pattern of elevated homocysteine alongside low B12 and folate is one of the most common and addressable biological signatures in mood presentations.

A standard GP assessment for low mood rarely includes the biomarkers most relevant to a biological investigation. TSH may be checked, and a basic blood count may identify severe anaemia, but Free T3, ferritin, vitamin D, folate, and homocysteine are typically absent. This means that many biological contributors to mood are simply not looked for.

A comprehensive blood panel for investigating low mood covers:

Vitamin D is among the most straightforward markers to check and the most commonly low. The test is a simple blood draw measuring 25-hydroxyvitamin D.

Vitamin B12 and folate provide a complete picture of methylation capacity and neurotransmitter substrate availability.

Ferritin is a more sensitive indicator of iron status than a blood count alone. Cognitive and mood effects can occur at ferritin levels above the clinical anaemia threshold.

TSH, Free T4, and Free T3 provide a complete thyroid assessment. TSH alone frequently misses early thyroid dysfunction and impaired T4-to-T3 conversion.

HbA1c assesses long-term blood sugar regulation and its relationship to metabolic inflammation.

CRP and homocysteine flag systemic inflammation and B-vitamin pathway disruption, both measurable contributors to mood.

Biomarker testing for low mood works best alongside, not instead of, any mental health support you are already receiving or considering. Identifying a low vitamin D level or impaired thyroid function does not replace talking therapy or psychiatric care; it identifies whether there is a biological layer that can be addressed alongside other approaches.

Address nutrient deficiencies systematically

The most meaningful intervention when a deficiency is confirmed is correcting it. Vitamin D supplementation shows the most consistent mood benefit in people with confirmed deficiency at baseline, with clinical trials using eight weeks or longer showing modest but meaningful improvements in depressive symptoms. B12 and folate can be increased through dietary changes (meat, fish, dairy, eggs for B12; leafy vegetables and legumes for folate) or supplementation when absorption is a concern. Iron-rich foods such as red meat, lentils, and fortified cereals support ferritin levels, with vitamin C enhancing absorption from plant sources. Testing before and after supplementation is the only reliable way to know whether levels have been restored.

Support thyroid function through nutrition and tracking

If thyroid markers are suboptimal, the co-factors that affect thyroid hormone production and conversion are worth addressing. Selenium (found in Brazil nuts, oily fish, and eggs) is required for T4-to-T3 conversion. Iodine (found in dairy, seafood, and some fortified foods) is the raw material for thyroid hormone synthesis. Ferritin, often low in people with thyroid symptoms, also affects conversion efficiency. Tracking TSH, Free T3, and the relevant co-factors over six to twelve months gives a clear signal of whether nutritional support is shifting the markers.

Stabilise blood sugar and reduce inflammation

Dietary patterns that reduce blood sugar variability, emphasise anti-inflammatory foods, and provide consistent protein for neurotransmitter synthesis provide a biological foundation for mood stability. Omega-3 fatty acids (from oily fish, walnuts, and flaxseed) have a well-evidenced anti-inflammatory and serotonin-supporting role. Reducing ultra-processed food and refined carbohydrates lowers the glucose variability and chronic inflammation that feed into mood dysregulation. Regular moderate exercise lowers CRP, supports dopamine activity, and produces measurable improvements in mood independent of other interventions.

Optimise sleep and circadian rhythm

The relationship between sleep and mood is bidirectional and strong. Poor sleep depresses serotonin and dopamine activity, elevates cortisol, and increases systemic inflammation. Consistent sleep timing, seven to nine hours of sleep, and limiting light exposure in the two hours before bed support melatonin production and the circadian rhythm that mood regulation depends on. Checking vitamin D and thyroid markers is particularly relevant for people whose low mood worsens seasonally, as both interact with circadian function.