Marlena Dudek-Makuch, Pharm. D., Development Expert, Curtis Health Caps
In 1982, the presence of receptors for vitamin D3 in the CNS was discovered in brain structures involved in, among other things, emotion and mood regulation processes (cingulate cortex, hippocampus, thalamus, hypothalamus), as well as the enzyme 1-hydrolase, which enables the conversion of vitamin D into its active form. Vitamin D3 has been shown to significantly affect CNS function by participating in neuromodulation processes, regulating the secretion of brain neurotropic factors, neuroprotection and neuroplasticity processes. The active vitamin D metabolite calcitriol (1,25-dihydroxycholecalciferol, 1,25(OH)2D3) has been shown to activate the expression of tyrosine hydroxylase, which is involved in the synthesis of catecholamines, increasing the production of dopamine, noradrenaline and adrenaline. It can also enhance cholinergic transmission by activating acetylcholinotransferase, an enzyme involved in the synthesis of acetylcholine. Vitamin D3 also increases levels of neurotropic growth factors, i.e. nerve growth factor (NGF) and glial-derived factor (GDNF), and neurotrophin 3 (NT-3). Studies have shown that dysfunction of NGF, NT-3 and GDNF may be important in the pathogenesis of depressive disorders and schizophrenia. In addition, vitamin D3 increases the synthesis of γ-glutamyltranspeptidase, an enzyme that is involved in the synthesis of glutathione, which has antioxidant functions in the brain. It therefore exhibits a protective effect against free radicals in the central nervous system [1].
Vitamin D and depression
Major Depressive Disorder (MDD) is characterised by, among other things, low mood, lowered self-esteem, loss of interest or pleasure in normally pleasurable activities and fatigue. It is a highly debilitating and prevalent disorder that occurs about twice as often in women as in men and affects 4.4-5% of the population [2]. Although the pathophysiology of MDD is complex, several mechanisms have been postulated to play a key role in the development of depressive symptoms, namely impaired neurotrophic support and neurogenesis, nervous system inflammation, disruption of bioenergetic signalling, and oxidative stress [3-6]. All of these changes can be induced by chronic stress, a condition that can cause activation of peripheral macrophages and central microglia, dysfunction of the hypothalamic-pituitary-adrenal axis and hypercortisolemia, with consequent impairment of synaptic plasticity and communication [5]. Given that vitamin D has extensive activity within the nervous system, its possible involvement in the prevention and/or treatment of depressive symptoms is under consideration [7-8].
Observational studies
A population-based study conducted in Norway in 2007-2008, involving 10086 patients, showed that low vitamin D3 levels may predispose to depressive disorders. The association between low vitamin D3 levels and the occurrence of depressive disorders was statistically significant, also after taking into account factors that may have influenced the results of the study, such as gender, physical activity, material status, chronic diseases, season, age, BMI The association between low vitamin D3 levels and the severity of depressive symptoms was greater in the female group [9].
Another study compared serum vitamin D3 levels in psychiatric inpatients who had made a suicide attempt with those diagnosed with depression but without a suicide attempt; healthy controls were included. The study included 59 psychiatrically treated patients who had made a suicide attempt, 17 patients with depression without a history of suicide attempts and 14 healthy subjects (control). In the group of patients who attempted suicide, mean vitamin D3 levels were significantly lower than in the group of depressed patients without suicide attempts and in the control group. In 58% of patients with a suicide attempt, high vitamin D3 deficiency (serum vitamin D3 levels <20 ng/ml) was found, whereas in the group of depressed patients who had never attempted suicide, vitamin D3 deficiency affected only 29% of the subjects [10].
Intervention studies
Positive effects of vitamin D supplementation in alleviating depression were reported in a group of Swedish adolescents (n = 48) aged 10-19 years. Vitamin D supplementation for a period of three months (4,000 IU/day for one month and 2,000 IU/day for two months) significantly reduced the severity of depression, irritability, fatigue, mood swings, sleep difficulties, weakness, and ability to concentrate in adolescents diagnosed with depression [12].
Another beneficial effect of vitamin D was reported in 2,839 Dutch men over 65 years of age. In this study, daily vitamin D supplementation (15 μg) for two years significantly reduced depressive symptoms [13].
A randomised, double-blind, placebo-controlled clinical trial of 40 patients aged 18-65 years with major depressive disorder showed that supplementation with a single dose of vitamin D (50000 IU/week for eight weeks) significantly reduced depressive symptoms [13]. Furthermore, a study involving patients with chronic liver disease (n = 111, median age: 55 years) showed that those who received 20000 IU of vitamin D/week for six months had reduced rates of depression after three and after six months of supplementation, with the best effects seen in women [14].
A more recent randomised trial was conducted to assess the effect of vitamin D supplementation on rates of perinatal depression in Iranian pregnant women (n = 136, age ≥18 years). The results showed that daily vitamin D intake (2000 IU), starting from 26-28 weeks until delivery, reduced perinatal depression rates [15].
On the other hand, some studies indicate that vitamin D supplementation has no effect on depression. A randomised clinical trial by Kjaergaard et al. assessed the effect of high-dose vitamin D3 supplementation (40 000 IU/week for six months) on adults (n = 230) aged 30-75 years. The results of this study showed no significant effect of high-dose vitamin D on depression rates compared to placebo [16].
Another randomised, double-blind US study involving 36,282 postmenopausal women aged 50-79 years investigated the effects of daily supplementation with vitamin D3 (400 IU) in combination with calcium (1,000 mg). This study showed that vitamin D supplementation did not prevent depression [17].
In chronic dialysis patients aged 18-60 years (comprising 382 haemodialysis and 102 peritoneal dialysis patients), oral administration of 0.5 μg/day of 1,25(OH)2D (calcitriol) for one year did not significantly reduce symptoms of depression [18].
Summary
Vitamin D deficiency may be one of the factors leading to depressed mood. Evidence of the potential impact of vitamin D levels on mood has been extensively documented in recent years. Several clinical trials have demonstrated the efficacy of vitamin D supplementation in the treatment of depression. Therefore, maintaining optimal vitamin D levels through sun exposure, diet and supplementation is a simple and effective way to prevent depression, especially in at-risk individuals such as pregnant women and the elderly. Vitamin D supplementation can be a safe, widely accepted, readily available and inexpensive treatment for depression. It can be used as a potential adjunctive therapy alongside existing treatment regimens to alleviate symptoms of depression.
Vaziri F, Nasiri S, Tavana Z, et al. BMC Pregnancy Childbirth 2016;16:239.
Kjaergaard M, Waterloo K, Wang CE, et al. Br J Psychiatry 2012; 201: 360-8.
Bertone-Johnson ER, Powers SI, Spangler L, et al. Am J Epidemiol 2012; 176: 1-13.
Zhang J, Zhang P, Ni X, et al. BMC Psychiatry 2014; 14: 125.
Biographical note
Dr n. farm. Marlena Dudek-Makuch,
Ekspert ds. Rozwoju w Curtis Health Caps, Wysogotowo.
Marlena Dudek-Makuch has 20 years of experience in phytochemical and biological research and scientific information (assistant professor at the Department of Pharmacognosy, Poznań University of Medical Sciences). She authored experimental and review papers on isolation and identification of compounds of plant origin and evaluation of their biological activity. Since 2015 she has been teaching postgraduate courses “Herbs in Practice and Therapy”. She currently works at CHC in the Regulatory Affairs Department of the R&D Division. She is responsible, among others, for preparing Expert Reports (clinical report, non-clinical report) for medicinal products, clinical report for changes in the availability category of a medicinal product (switch OTC), clinical assessment for medical devices and conducting activities in the area of safety supervision of medical devices, as well as safety assessment of plant raw materials used in medicinal products, medical devices and dietary supplements. She is a member of the Polish Herbal Committee.
