CLAIM:
Low levels of Vitamin D and Vitamin B12 mean a person is “100 per cent depressed,” even if they are unaware of it. Nearly all patients with depression have deficiencies in these vitamins, and correcting them is essential.
FACT:
Low levels of Vitamin D and Vitamin B12 have been associated with higher rates of depressive symptoms in several observational studies. However, current evidence does not prove that these deficiencies directly or universally cause depression. There is a need for more robust, randomised controlled trials to establish causation.
In a viral reel posted by Instagram handle ‘mentalwellnesscentre’, Dr Pankaja Singh links Vitamin D and Vitamin B12 deficiencies directly to depression.
Vitamin D and depression
Research suggests that low Vitamin D levels are associated with higher rates of depressive symptoms, and there may be a biological overlap. But major studies consistently stop short of declaring a direct, universal, or deterministic cause, indicating the need for more randomised controlled trials.
A 2013 systematic review and meta-analysis analysed 14 studies involving 31,424 participants, including cross-sectional, cohort and case-control studies. The researchers found that people with the lowest vitamin D levels were more likely to have depression, and over time, they also showed a higher risk of developing depression compared to those with higher vitamin D levels.
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However, the authors were cautious in their interpretation. “Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal,” they concluded.
A decade later, a 2023 study examined 15,156 adults aged 20 years or older. Depression was assessed using the PHQ-9 scale, and vitamin D deficiency was defined as serum levels below 30 nmol/L. The researchers found that vitamin D levels were negatively associated with depression. Even after adjusting for confounding variables, vitamin D deficiency remained significantly linked with higher depression risk.
The study concluded that “vitamin D deficiency and older age are both associated with higher risk of depression, while older age is a protective factor for vitamin D deficiency.”
More recently, a 2025 genome-wide association study (GWAS) involving over 5.89 lakh individuals with depression data and over 4.17 lakh individuals with vitamin D data explored whether there is a shared biological basis between the two. Researchers found a small but significant negative genetic correlation and identified 410 overlapping genetic variants. Several shared genes - including TRMT61A, ITIH4, ESR1 and GRM5- showed expression patterns linked to brain development.
“Our findings elucidate the shared biological mechanisms underlying the relationship between vitD and depression, suggesting that vitD play an important role in the development of depression through altered early neurodevelopmental processes,” the authors concluded.
However, even this large genetic study examined shared pathways and potential mechanisms, not proof that low vitamin D levels alone make a person “100% depressed.”
Is vitamin B12 deficiency linked to depression?
Research suggests that low Vitamin B12 levels, especially when accompanied by elevated homocysteine, may be associated with depression, and in some studies, with greater severity. However, results are not entirely consistent across populations. Some research finds a significant association, while other studies do not observe a clear independent link.
A 2020 case-control study compared 89 children and teenagers with depression to 43 young people without any mental health diagnosis. Researchers tested their blood for vitamin B12, vitamin D, folate and homocysteine levels. They found that those with depression had significantly lower levels of vitamin B12 and vitamin D, and higher levels of homocysteine. There was no major difference in folate levels between the two groups.
The researchers also observed that depression severity was negatively correlated with vitamin B12 and vitamin D levels, and positively correlated with homocysteine. They concluded that “the results of the study show that vitamin B12 deficiency or insufficiency and elevated homocysteine may contribute to the etiopathogenesis of depression.”
However, they also emphasised that there are limited studies in children and adolescents and recommended further investigation of these biochemical markers in young patients with depression.
Moving to adults, a 2023 case-control study involving 81 individuals with depression and 95 control subjects assessed vitamin D, B12 and folate levels. While vitamin D deficiency was strongly associated with depression, with deficient individuals having nearly four times higher odds, the findings for vitamin B12 were different. The study reported that “there was no significant association identified between the case and control group with respect to serum vitamin B12 and folate levels.”
The authors concluded that vitamin D deficiency showed an association with depression, but stressed that “further research studies are needed to validate its correlation to the etiopathogenesis of depression.” In other words, even here, vitamin B12 did not emerge as a clear independent risk factor.
A 2024 study focusing specifically on patients with Major Depressive Disorder (MDD), recruited using ICD-10 criteria, found more striking results. Among 59 patients, “vitamin B12 was deficient or depleted in all patients with MDD.” The median serum B12 level was 164.2 pg/ml and was significantly lower in patients with severe MDD. Homocysteine levels were also elevated, with a mean value of 18.34 μmol/L.
The researchers concluded that “vitamin B12 deficiency is found in patients with MDD and varies inversely with the severity of MDD. Hcy (homocysteine) is found to be higher in patients with MDD.”
They further noted that in their study, depressive symptoms appeared before the more commonly recognised haematological signs of B12 deficiency.
This story is done in collaboration with First Check, which is the health journalism vertical of DataLEADS.
