Depression is especially reduced by large intermittent doses of vitamin D – meta-analysis – April 2023

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Efficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trials

Nutrition 2023 Jan 7;108:111968. doi: 10.1016/j.nut.2022.111968 PDFis behind a paywall
Maytinee Srifuengfung 1, Somporn Srifuengfung 2, Chalermsri Pummangura 2, Keerati Pattanaseri 1, Awirut Oon-Arom 3, Manit Srisurapanont 4

Objectives: This systematic review and meta-analysis synthesized the evidence from randomized controlled trials comparing vitamin D and placebo in reducing depressive symptoms and contributing to all-cause dropout rates.

Methods: Inclusion criteria were randomized controlled trials comparing reduced depression between depressed patients receiving vitamin D and those receiving placebo. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through January 2022.

Results: Eighteen trials (1980 participants, median age 39 y) were included in the meta-analysis. Vitamin D supplements were significantly superior to placebo in reducing depression (standardized mean difference = -0.49; 95% confidence interval CI, -0.75 to -0.23; I2 = 81%). Depressed adults (standardized mean difference = -0.70; 95% CI, -1.09 to -0.31) responded to vitamin D significantly better than children and adolescents (standardized mean difference = 0.10; 95% CI -0.27 to 0.47).
Vitamin D administered as bolus doses (oral intermittent high doses or intramuscular single high dose) appeared to be more effective than that taken daily by the oral route (P < 0.01).
Patients with more severe depression tended to respond better than those with less severity (P = 0.053). We found no moderating effect of concurrent antidepressant use, presence of major depressive disorder diagnosis, physical comorbidity, sex, duration and doses of vitamin D supplement, serum 25-hydroxyvitamin D levels at baseline, and changes in serum 25-hydroxyvitamin D levels in the vitamin D group. Dropout rates were indifferent between the groups (17 trials; risk ratio = 0.84; 95% CI, 0.6-1.16; I2 = 0).

Conclusions: Heterogeneous data suggested that vitamin D supplements are effective and safe for depressed patients.

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18 Meta-analyses of Vitamin D and Depression in VitaminDWiki

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VitaminDWiki – Depression summary contains

• Low vitamin D is associated with most types of depression, Including: Seasonal Affective Disorder. manic depression, bipolar disorder, dysthymia, Depression during/after pregnancy, Seniors, Suicide
• Depression substantially reduced by Vitamin D, Omega-3, Magnesium, etc – many studies
• Depression 1.6 X more likely if low Vitamin D, taking Vitamin D reduces depression – umbrella of meta-analyses – Jan 2023
• Depression: Low vitamin D in the strongest of 11 risk factors – Jan 2023
• Yet another study confirms Depression is treated by weekly Vitamin D (50,000 IU)– RCT Dec 2019
• Depression treated by Omega-3 (again) – meta-analysis Aug 2019
• Supplementing with Vitamin D (or getting more sun) decreases most types of depression as well as drugs
• Omega-3, Magnesium, and St. Johns' Wort also decrease depression
  • Speculate that some combination (Vit D, Omega-3, Mg, St John's) will decrease depression even more
  • Note: Both Omega-3 and Magnesium increase the amount of vitamin D which gets to tissues
• Antidepressants reduce cellular Vitamin D, increasing fractures, CVD, etc. - Oct 2022
• There are 266 items in the Depression category in VitaminDWiki

Some recent publications

• Depression in seniors greatly reduced by Vitamin D (50,000 IU weekly) – meta-analysis June 2023
• Depression reduced if take more than 5,000 IU of vitamin D daily – umbrella meta-analysis – Jan 2023
• Post-partum depression and low Vitamin D - many studies
• Depression: Low vitamin D in the strongest of 11 risk factors – Jan 2023

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VitaminDwiki – Better than Daily contains

32 items in BETTER THAN DAILY category

Non-daily (Bolus) is better:

1. Better compliance for everyone
   • Fewer opportunities to forget.
   • If happen to forget, just take the dose many days later
   • Fewer times to have to take a pill - for those who dislike doing so
2. Non-daily gets more vitamin D to the cells for the ~20% who have a poor Vitamin D Receptor
   • A high concentration gradient is one of 14+ ways to get past Vitamin D Receptor limitations
   • So, while 80% get no extra benefit from non-daily dosing, 20% will get an extra benefit

• Vitamin D given daily, weekly, or monthly has similar response (116 RCTs) – meta-analysis Aug 2023
• 44 percent of successful RCTs in VitaminDWiki used non-daily dosing - Nov 2020
• Monthly vitamin D dosing better for children than daily (again) - Oct 2023

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VitaminDwiki – Diseases treated by high-dose Vitamin D - many studies