Evidence-Based Reviews

Vitamin deficiencies and mental health: How are they linked?

Author and Disclosure Information

Identifying and correcting deficiencies can improve brain metabolism and psychopathology



Discuss this article at www.facebook.com/CurrentPsychiatry

Patients today often are overfed but undernourished. A growing body of literature links dietary choices to brain health and the risk of psychiatric illness. Vitamin deficiencies can affect psychiatric patients in several ways:

  • deficiencies may play a causative role in mental illness and exacerbate symptoms
  • psychiatric symptoms can result in poor nutrition
  • vitamin insufficiency—defined as subclinical deficiency—may compromise patient recovery.

Additionally, genetic differences may compromise vitamin and essential nutrient pathways.

Vitamins are dietary components other than carbohydrates, fats, minerals, and proteins that are necessary for life. B vitamins are required for proper functioning of the methylation cycle, monoamine production, DNA synthesis, and maintenance of phospholipids such as myelin (Figure). Fat-soluble vitamins A, D, and E play important roles in genetic transcription, antioxidant recycling, and inflammatory regulation in the brain.

Figure: The methylation cycle
Vitamins B2, B6, B9, and B12 directly impact the functioning of the methylation cycle. Deficiencies pertain to brain function, as neurotransmitters, myelin, and active glutathione are dependent on one-carbon metabolism
Illustration: Mala Nimalasuriya with permission from DrewRamseyMD.com

To help clinicians recognize and treat vitamin deficiencies among psychiatric patients, this article reviews the role of the 6 essential water-soluble vitamins (B1, B2, B6, B9, B12, and C; Table 1,1) and 3 fat-soluble vitamins (A, D, and E; Table 2,1) in brain metabolism and psychiatric pathology. Because numerous sources address using supplements to treat vitamin deficiencies, this article emphasizes food sources, which for many patients are adequate to sustain nutrient status.

Table 1

Water-soluble vitamins: Deficiency, insufficiency, symptoms, and dietary sources

DeficiencyInsufficiencySymptomsAt-risk patientsDietary sources
B1 (thiamine): Glycolysis, tricarboxylic acid cycle
Rare; 7% in heart failure patients5% total, 12% of older womenWernicke-Korsakoff syndrome, memory impairment, confusion, lack of coordination, paralysisOlder adults, malabsorptive conditions, heavy alcohol use. Those with diabetes are at risk because of increased clearancePork, fish, beans, lentils, nuts, rice, and wheat germ. Raw fish, tea, and betel nuts impair absorption
B2 (riboflavin): FMN, FAD cofactors in glycolysis and oxidative pathways. B6, folate, and glutathione synthesis
10% to 27% of older adults<3%; 95% of adolescent girls (measured by EGRAC)Fatigue, cracked lips, sore throat, bloodshot eyesOlder adults, low intake of animal and dairy products, heavy alcohol useDairy, meat and fish, eggs, mushrooms, almonds, leafy greens, and legumes
B6 (pyridoxal): Methylation cycle
11% to 24% (<5 ng/mL); 38% of heart failure patients14% total, 26% of adultsDermatitis, glossitis, convulsions, migraine, chronic pain, depressionOlder adults, women who use oral contraceptives, alcoholism. 33% to 49% of women age >51 have inadequate intakeBananas, beans, potatoes, navy beans, salmon, steak, and whole grains
B9 (folate): Methylation cycle
0.5% total; up to 50% of depressed patients16% of adults, 19% of adolescent girlsLoss of appetite, weight loss, weakness, heart palpitations, behavioral disordersDepression, pregnancy and lactation, alcoholism, dialysis, liver disease. Deficiency during pregnancy is linked to neural tube defectsLeafy green vegetables, fruits, dried beans, and peas
B12 (cobalamin): Methylation cycle (cofactor methionine synthase)
10% to 15% of older adults<3% to 9%Depression, irritability, anemia, fatigue, shortness of breath, high blood pressureVegetarian or vegan diet, achlorhydria, older adults. Deficiency more often due to poor absorption than low consumptionMeat, seafood, eggs, and dairy
C (ascorbic acid): Antioxidant
7.1%31%Scurvy, fatigue, anemia, joint pain, petechia. Symptoms develop after 1 to 3 months of no dietary intakeSmokers, infants fed boiled or evaporated milk, limited dietary variation, patients with malabsorption, chronic illnessesCitrus fruits, tomatoes and tomato juice, and potatoes
EGRAC: erythrocyte glutathione reductase activation coefficient; FAD: flavin adenine dinucleotide; FMN: flavin mononucleotide
Source: Reference 1

Table 2

Fat-soluble vitamins: Deficiency, insufficiency, symptoms, and dietary sources

DeficiencyInsufficiencySymptomsAt-risk patientsDietary sources
A (retinol): Transcription regulation, vision
<5% of U.S. population44%Blindness, decreased immunity, corneal and retinal damagePregnant women, individuals with strict dietary restrictions, heavy alcohol use, chronic diarrhea, fat malabsorptive conditionsBeef liver, dairy products. Convertible beta-carotene sources: sweet potatoes, carrots, spinach, butternut squash, greens, broccoli, cantaloupe
D (cholecalciferol): Hormone, transcriptional regulation
≥50%, 90% of adults age >5069%Rickets, osteoporosis, muscle twitchingBreast-fed infants, older adults, limited sun exposure, pigmented skin, fat malabsorption, obesity. Older adults have an impaired ability to make vitamin D from the sun. SPF 15 reduces production by 99%Fatty fish and fish liver oils, sun-dried mushrooms
E (tocopherols and tocotrienols): Antioxidant, PUFA protectant, gene regulation
Rare93%Anemia, neuropathy, myopathy, abnormal eye movements, weakness, retinal damageMalabsorptive conditions, HIV, depressionSunflower, wheat germ, and safflower oils; meats; fish; dairy; green vegetables
HIV: human immunodeficiency virus; PUFA: polyunsaturated fatty acids; SPF: sun protection factor
Source: Reference 1

Water-soluble vitamins

Vitamin B1 (thiamine) is essential for glucose metabolism. Pregnancy, lactation, and fever increase the need for thiamine, and tea, coffee, and shellfish can impair its absorption. Although rare, severe B1 deficiency can lead to beriberi, Wernicke’s encephalopathy (confusion, ataxia, nystagmus), and Korsakoff’s psychosis (confabulation, lack of insight, retrograde and anterograde amnesia, and apathy). Confusion and disorientation stem from the brain’s inability to oxidize glucose for energy because B1 is a critical cofactor in glycolysis and the tricarboxylic acid cycle. Deficiency leads to an increase in reactive oxygen species, proinflammatory cytokines, and blood-brain barrier dysfunction.2 Wernicke’s encephalopathy is most frequently encountered in patients with chronic alcoholism, diabetes, or eating disorders, and after bariatric surgery.3 Iatrogenic Wernicke’s encephalopathy may occur when depleted patients receive IV saline with dextrose without receiving thiamine. Top dietary sources of B1 include pork, fish, beans, lentils, nuts, rice, and wheat germ.


Recommended Reading

Depressed RA patients more likely to die, especially men
MDedge Psychiatry
Using SSRIs in pregnancy
MDedge Psychiatry
DSM-5 Cleared for Takeoff
MDedge Psychiatry
SSRI antidepressants safe for depressed epilepsy patients
MDedge Psychiatry
Snapshot after diagnosis: prevalence of distress varies by cancer, gender, and age
MDedge Psychiatry
Links found between episodes of mood disorders, childbirth
MDedge Psychiatry
Preventing suicide preceded by mass murder
MDedge Psychiatry
Deficits in empathic abilities appear to be disorder specific
MDedge Psychiatry
Poverty's Effect on Mental Health
MDedge Psychiatry
Monoamine oxidase inhibitors: Forgotten treatment for depression
MDedge Psychiatry