More vitamin D needed, unsure level needed and for how long (depression in this case) – Review Aug 2021

Adverse health outcomes in vitamin D supplementation trials for depression: a systematic review

Ageing Research Reviews https://doi.org/10.1016/j.arr.2021.101442
Karen S.van den BergabRadboud M.MarijnissenbRob H.S.van den BrinkbRichard C.Oude VoshaarbJohanna M.Hegemana

 Download the PDF from VitaminDWiki

Only rarely did the actual Vitamin D response reach the the expected response
Note: Non-daily dosing is the most common
   (subset of table)

Background
Vitamin D deficiency is a universal risk factor for adverse health outcomes. Since depression is consistently associated with low vitamin D levels as well as several adverse health outcomes, vitamin D supplementation may be especially relevant for depressed persons. This review examines the potential benefits of vitamin D for (somatic) health outcomes in randomised controlled supplementation trials for depression.

Method
Systematic literature search to assess whether adverse health outcomes, such as frailty, falls, or cognitive functioning, were included in vitamin D supplementation trials for depression, and whether these outcomes were affected by supplementation. The revised Cochrane tool for assessing risk of bias in randomised trials was used.

Results
Thirty-one trials were included. Adverse health outcomes were considered in five studies. Two studies reported some beneficial effect on an adverse health outcome.

Conclusions and implications
While depressed persons are at increased risk of vitamin D deficiency, supplementation trials hardly addressed the common negative health consequences of low vitamin D levels as secondary outcome measures. Well-designed trials of the effects of vitamin D supplementation in late-life depression should explore whether adverse health outcomes can be prevented or stabilised, and whether depression benefits from this improvement.
- - - - - - - - -

4.2 Supplementation recommendations

Although supplementation of 10-20 pg vitamin D per day (depending on skin colour and sun exposure) is recommended for all older persons (Health Council of the Netherlands, 2012), these guidelines are often not followed (Chel et al., 2013). In the Netherlands, general practitioners are encouraged to follow a pragmatic approach and to actively prescribe vitamin D to persons who will likely benefit from it (Elders et al., 2015). So far, depressed persons are not one of the risk groups explicitly identified in these guidelines.
While vitamin D levels of 75 nmol/l are considered sufficient for bone metabolism and the prevention of falls and fractures (American Geriatrics Society Workgroup on vitamin D supplementation for older adults, 2014; Bisschoff-Ferrari, 2007), target levels for extra- skeletal effects are unknown. Moreover, while dose-response curves are often non-linear (see Heaney, 2014), a recent dose-response meta-analysis that specifically looked for non-linear dose-response associations between vitamin D levels and depression, only found a linear association (Li et al., 2019). Therefore, future supplementation trials should not only address what the optimal vitamin D level should be, but also whether the dose-response curve for these effects is linear or non-linear. Interestingly, the beneficial effect of vitamin D supplementation on the number of functional limitations in the high-quality D-Vitaal study (De Koning et al., 2019) was only seen in the subgroup with baseline vitamin D levels >50 nmol/l. This post-hoc analysis could be a chance finding, but if not, several explanations may apply.

• First, in case of severe vitamin D deficiency irreversible effects may have occurred, or
• secondly, higher target values and/or a longer follow-up duration are needed to improve functional limitations.

This latter explanation also challenges the idea of fixed target levels for specific outcomes, as target levels may differ conditional on duration and severity of vitamin D deficiency. Finally, the target level of vitamin D to improve functional limitations in depression might be much higher than previously thought and may only be reached by this supplementation strategy among patients who had >50 nmol/l vitamin D levels at baseline. Regarding the uncertainty of optimal vitamin D levels in depression, we advocate considering depressed persons as at risk for vitamin D deficiency and the associated adverse health outcomes.