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- Low vitamin B12 and vitamin D levels, along with increased homocysteine, may play a role in depression among children and adolescents
- While there was no significant difference in folate levels between the depression and control groups, 11.23% of those with depression had low levels of folate
- Both vitamin B12 and folate have previously been described as antidepressant nutrients; folate is found in dark leafy greens like spinach and avocados while vitamin B12 is found only in animal foods such as grass fed meat, eggs, dairy and wild-caught seafood
- Vitamin B12 also helps regulate homocysteine levels, and increased homocysteine is linked to B12 deficiency as well as depression
- Ensuring youth are eating healthy diets rich in folate and vitamin B12, as well as optimizing their vitamin D levels, may go a long way toward bolstering mental health and avoiding conditions like depression
This article was previously published July 2, 2020, and has been updated with new information.
Up to 2.5% of children and 8.3% of adolescents suffer from depression, a condition that's associated with significant complications later in life, including an increased risk of suicide, substance abuse, physical diseases and problems with work, academic and psychosocial functioning.1
It's believed that both genetic and environmental factors play a role in why some children develop depression, and increasing attention has been placed on the role of dietary factors and nutrients such as vitamin D, which is ideally obtained via sun exposure.
Further, one-carbon metabolism, which includes vitamin B12, folate and homocysteine and which plays a role in many biological processes and maintaining cellular homeostasis, has been investigated for its role in psychiatric disorders, including depression in adults.2
After exploring the link further, researchers from Ordu University in Turkey revealed that low vitamin B12 and vitamin D levels, along with increased homocysteine, may play a role in depression among children and adolescents.3
Childhood Depression Linked to Low Vitamin B12, Maybe Folate
The study involved 89 children and adolescents with depression, along with 43 subjects without depression to serve as controls. The volunteers completed testing for childhood depression and anxiety and had their levels of folate, vitamin B12, homocysteine and vitamin D measured.
While there was no significant difference in folate levels between the groups, 11.23% of those with depression had low levels of folate. Further, among the depression group vitamin B12 and vitamin D levels were "clearly low." As for how this might contribute to depression, the researchers explained:4
"One-carbon metabolism has a basic role in methylation processes of neurotransmitters, proteins, and membrane phospholipids. Additionally, it is necessary for DNA synthesis.
With vitamin B12 and folate deficiency, methylation processes are hindered and neurotransmitter levels fall. Also linked to vitamin B12 and folate deficiency, there is an increase in the levels of the extremely neurotoxic metabolite of homocysteine."
Both vitamin B12 and folate have previously been described as antidepressant nutrients.5 Folate, found in dark leafy greens like spinach, avocados and other fresh vegetables, is involved in your body's production of mood-regulating neurotransmitters. In one study, people who consumed the most folate had a lower risk of depression than those who ate the least.6
Vitamin B12 is found only in animal foods such as grass fed meat, eggs, dairy and wild-caught seafood. As such, vegetarians and vegans are especially susceptible to B12 deficiency, and this is one likely reason why vegetarianism may be nearly twice as likely to suffer from depression as meat eaters, even after adjusting for variables like job status, family history and number of children.7
It's widely known that people with a vitamin B12 deficiency are at an increased risk of depression,8which could be, in part, due to resulting alterations in the level of DNA methylation in the brain, leading to neurologic impairment.9 Vitamin B12 also helps regulate homocysteine levels, and increased homocysteine is linked to B12 deficiency as well as depression.
Folate, Vitamin B12 Suggested for Treatment of Depression
Considering the extensive research linking depression with low levels of vitamin B12 and folate, researchers with the MRC Neuropsychiatric Research Laboratory in Epsom, Surrey, U.K., suggested that folate and vitamin B12 should be considered in the treatment of depression.
"On the basis of current data, we suggest that oral doses of both folic acid (800 mcg daily) and vitamin B12 (1,000 mcg daily) should be tried to improve treatment outcome in depression," they noted.10
Folic acid is the synthetic version of folate, or vitamin B9, and while it may have a place in depression treatment, the best way to increase your levels is to eat foods rich in folate, such as asparagus, avocados, Brussels sprouts, broccoli and spinach. As for why folate and vitamin B12 are so important for mental health, they explained:11
"Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients."
Depressed Children Had 'Remarkably High' Homocysteine Levels
The connection between low vitamin B12 and increased homocysteine levels is notable, as the featured study found "remarkably high" homocysteine levels in the children and adolescents with depression.
"Increased homocysteine increases the flow of calcium within cells through the NMDA [N-methyl D-aspartic acid] receptor activation pathway. Within the cell, oxidative stress increases and apoptotic signals are activated. Increased homocysteine causes DNA damage, mitochondrial dysfunction, and endoplasmic reticulum stress," the researchers noted, suggesting that this is likely one mechanism behind homocysteine's depression connection.12
Separate research has also linked higher homocysteine levels with increased rates of depression and anxiety among 12- and 13-year-old boys in Taiwan.13 Higher levels of homocysteine, along with significantly lower levels of vitamin B12 and vitamin D, are also associated with other mental health conditions, including obsessive compulsive disorder, in which it's believed to play a causative role.14
Homocysteine is an amino acid in your body and blood obtained primarily from meat consumption. Vitamins B6, B9 and B12 help convert homocysteine into methionine — a building block for proteins. If you don't get enough of these B vitamins, this conversion process is impaired and results in higher homocysteine. Conversely, when you increase intake of B6, folate and B12, your homocysteine level decreases.
As such, checking your homocysteine level is a great way to identify a vitamin B6, folate and B12 deficiency. The researchers also noted that "vitamin deficiencies and elevated homocysteine should be investigated in terms of cause-effect relationships" in terms of depression in youth, especially since depression may contribute to poor appetite and irregular eating habits.
Vitamin D Levels Also Low Among Depressed Youth
The Ordu University researchers also found vitamin D levels to be low among the children and adolescents with depression, a connection that's been revealed in the past. In the study, the depressed group had a median vitamin D level of 11 ng/ml, compared to 24.85 ng/ml in the control group. Both of these values are low, but 11 ng/ml is dangerously low and will radically increase the risk of rickets.
It's important to note that for optimal health and disease prevention, a level between 60 and 80 ng/mL (150 to 200 nm/L) appears to be ideal, so all of the study participants were very low by this measure. Vitamin D receptors exist in the human brain,15 hinting at the importance of this vitamin in mental and emotional health.