Exploring the Effects of Vitamin D Supplementation on Cognitive Functions and Mental Health Status in Subjects Under Methadone Maintenance Treatment

Abstract

Objectives: Vitamin D deficiency may be linked to several mental complications including cognitive deficits, depression, and anxiety in patients under methadone maintenance treatment (MMT). This study was designed to explore the effect of vitamin D supplementation on cognitive functions and mental health parameters in subjects under MMT. Methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out among 64 patients under MMT. Participants were randomly allocated to receive either 50,000 IU vitamin D supplements (n = 32) or placebo (n = 32) every 2 weeks for 24 weeks. Cognitive functions and mental health parameters were taken at baseline and posttreatment to evaluate relevant variables. Results: After the 24-week intervention, compared with the placebo, serum 25(OH) vitamin D levels significantly increased in participants who received vitamin D supplements (β 14.50; 95% confidence interval [CI], 13.17–15.83; P < 0.001). In addition, compared with the placebo, subjects who received vitamin D had a significant reduction in Iowa Gambling Task (β −6.25; 95% CI, −8.60 to −3.90; P < 0.001), and significant increases in Verbal Fluency Test (β 2.82; 95% CI, 0.78–4.86; P = 0.007), Immediate Logic Memory (β 1. 32; 95% CI, 0.27–2.37; P = 0.01), Reverse Digit Span (β 2.06; 95% CI, 1.18–2.94; P < 0.001) and visual working memory (β 0.75; 95% CI, 0.33–1.16; P = 0.001). Also, vitamin D supplementation significantly improved BDI (β −2.76; 95% CI, −3.97 to −1.55; P < 0.001) compared with the placebo. When we applied Bonferroni correction, LM-Immediate (P = 0.07) became nonsignificant, and other mental health parameters did not alter. Conclusions: Overall, taking 50,000 IU vitamin D supplements every 2 weeks for 24 weeks by patients under MMT had beneficial effects on cognitive functions and some mental health parameters. Further studies are needed to confirm our findings.

Putative role of vitamin D in the mechanism of alcoholism and other addictions – a hypothesis

“…This justifies a hypothesis which proposes that the functioning of the PFC may adequately reflect cerebral vitamin D status. The results of Wrzosek et al (2014) and those of Ghaderi et al (2017Ghaderi et al ( , 2020 possibly also correspond to an effect within the prefrontal cerebral cortex.…”

“…Measuring the activity of the frontal cerebral cortex by means of a neuropsychological test battery reflecting COMT activity might be suitable to assess the cerebral vitamin D status in this type of pharmacogenetic research (cf. Ehlis et al, 2007;Ghaderi et al, 2020). Once the relationship with serum calcidiol levels and relevant genotypes is established, corrected calcidiol levels could be applied for therapeutic monitoring.…”

“…After screening the summaries, some content duplicates and all irrelevant studies were removed (Table 1). As a result, we identified only five studies which specifically addressed the subject: one narrative review of animal data (Eserian, 2013); one systematic review (Tardelli et al, 2017); one cross-sectional genetic association study (Wrzosek et al, 2014) and two relevant clinical studies (Ghaderi et al, 2017(Ghaderi et al, , 2020 regarding the relationship of vitamin D with addiction (Table 2). Nevertheless, these studies were considered to be of interest for theory formation as is discussed below.…”

“…This might be related to an inability to drink alcohol in a controlled manner. Ghaderi et al (2017Ghaderi et al ( , 2020 published the results of two randomised controlled trials of 50 000 IU of vitamin D or matching placebo taken every 2 weeks for 12 and 24 weeks, respectively. The level of blindness was not specified.…”

“…Exploring the effects of vitamin D supplementation on cognitive functions and mental health status in subjects under methadone maintenance treatment (Ghaderi et al, 2020) Iran, 2019…”