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Vitamin D for MDD

Major depressive disorder (MDD) is a condition without many effective treatments, or at least treatments lacking side effects. Vitamin D has been linked to improved mood, and this trial tested it specifically for MDD

Study under review: Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial


Everyone feels sad sometimes. For some people, however, sadness can grow into a debilitating medical condition known as depression, or major depressive disorder (MDD). MDD is quite prevalent, affecting approximately 20% of people at some point in their lifetime[2], and has been linked to other physiological complications, such as increased risk of cardiovascular disease, dyslipidemia, diabetes and hypertension[3]. Increase in oxidative stress in MDD patients[4] has also been reported. Overall, MDD patients have been shown to have decreased lifespan and quality of life[5].

Vitamin D is a fat-soluble secosteroid (a steroid with an “open” ring) that enhances absorption of essential elements, such as magnesium, iron, calcium, phosphate, and zinc. Traditionally, the majority of vitamin D has been obtained from exposure to sunlight. It is also available through dietary consumption, mostly through fortified foods like milk and cereal. Vitamin D obtained from sunlight or diet requires hydroxylation (addition of a hydroxyl “–OH” group) in the liver to become biologically active.

There are two major forms of vitamin D: D2 (ergocalciferol, obtained from foods) and D3 (cholecalciferol, synthesized following exposure to sunlight). Collectively, both isoforms are termed calciferol. Calciferol is converted into calcidiol, a parahormone, in the liver, and subsequently converted into the biologically active form calcitriol in the kidneys. Calcitriol binds the nuclear vitamin D receptor, which is ubiquitously expressed, inducing transcription of various target genes. Vitamin D plays an important role in proper bone formation and maintenance of bone density[6], along with a possible role in the immune system[7]. Vitamin D deficiency has been associated with a variety of diseases, including osteoporosis[8], neurodegenerative diseases[9], cardiovascular disease[10], and complications during pregnancy[11].

Serum vitamin D levels have also been negatively correlated with depressive symptoms[12]. Recent meta-analyses[13] have shown a connection between higher serum vitamin D levels and improved depressive symptoms in people with MDD. There are also a number of studies on the effects of various levels of vitamin D supplementation in MDD patients. Some studies suggest no benefits of vitamin D to mood symptoms of MDD; however, a meta-analysis of existing studies concluded that vitamin D supplementation of 800IU per day or more[14] in vitamin D deficient patients has a positive impact on MDD mood symptoms.

In addition to a positive effect on mood, vitamin D supplementation has been shown[15] to have a positive effect on glucose and cholesterol levels in pregnant women with gestational diabetes (high blood sugar during pregnancy). Recent meta-analyses have indicated that type 2 diabetes is significantly more common in MDD patients[16], and markers of oxidative stress are elevated in MDD patients[17]. Since the researchers behind the current study have recently shown that high-dose vitamin D supplementation improves glucose levels, oxidative stress and inflammation in type 2 diabetes patients[15], in this study they wanted to investigate the effect of vitamin D supplementation on oxidative stress and blood glucose in MDD patients, as well as the effect on mood change.

Vitamin D supplementation has been shown to be beneficial in studies on depression and metabolic disorders; however, no studies have investigated effects of vitamin D supplementation on both mood and metabolic markers in a population of MDD patients. This study was designed to investigate the benefits of high-dose 8-week vitamin D supplementation in MDD patients.

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