Here is a music selection for the Sunday morning reflective crowd: Chopin's Ballade No. 4
And let's just get it over with: Vitamin D Supplementation and Depression in the Women's Health Initiative Calcium and Vitamin D Trial.
Okay, HUGE double blind randomized controlled trial. Over 36,000 women, randomized to placebo or 1000 mg calcium + 400 IU vitamin D3 daily for 3 years. Depression scores were measured via questionnaire (one I've never heard of, the Bernam scale) and antidepressant use (maybe problematic because different classes of antidepressants have varying uses, for example, TCAs are prescribed for migraines and chronic diarrhea, and SSRIs are used for anxiety) at baseline and several follow up points. In addition, a subset (828 women) actually had D levels measured during the trial. Beginning average level was 52 nmol/L which is about 20.8 ng/ml in the units I will typically see on a lab report form. After two years (and measuring a separate group of 400 some-odd people), the average level in the supplemented group was 28% higher than those who were not supplemented. (Assuming a similar 20.8 ng/ml starting point, two years of D supplementation increased levels to 26.6.)
Kinda scary that the average level of these women at the beginning is just a tick north of absolutely deficient even according to the conservative Institutes of Medicine. 400IU does seem to prevent rickets, and it is similar to the amount of oral vitamin D one might be expected to get from eating cold marine animals. But it certainly doesn't make up for recommending the entire population avoid the sun at all costs.
In the end, supplementation with 400IU Vitamin D3 (and calcium) was associated with an increased chance of reporting depressive symptoms (the odds ratio was 1.16, though, not too terribly exciting) and not associated antidepressant use compared to placebo.
I'm not surprised, and I'm somewhat annoyed with vitamin D studies and depression at this point. Studies tend to use teensy levels or enormous ones (and please see that link for a round-up of the relevant D and mental health studies.) Why don't we find a middle ground between 400IU and 500,000IU (literally)?
I'll share my clinical experience, which, being anecdotal, may not be worth much. I've been more aggressive about measuring vitamin D in the last few years (as have the internists I work with), and I would say roughly 1/3 of the folks I measure (or have had a D measured in the past year by the primary care doctor) are absolutely deficient. Meaning below 20 ng/ml. Levels between 10-15 are common, but I've seen 4s and 8s as well. The super low folks have tended to have a "sick" look: pale, circles under the eyes, bloated, tired. (Though not everyone who is pale and tired has a low D by any means!) If I had to guess from just looking at them, I would think they might be fighting a cold or were hypothyroid. Most of the time, the thyroid function is absolutely normal.
Most of the folks I see have depression, and typically some sort of resistant depression, and I would say 99% of people come to me having already been put on psych meds of some kind. It's a bit hard to generalize, each patient has his or her own particular circumstances, character strengths, education, and external stressors� but I've figured out that some long-term patients with ultra-low vitamin D finally responded to all the psychiatry mucking around (bolstering supports, lifestyle interventions, therapy, medication adjustment) after the D was corrected. Shorter term patients have looked better and done better since getting D out of the basement. I've never attempted an isolated D intervention (which wouldn't be standard of care by any means).
So, while resistant depression generally requires a lot of adjustments in different areas of life to get trending a better direction and to get people more functional and happier, I surmise that replenishing super-deficient vitamin D may be one of those adjustments that ought to be done and likely won't hurt, and seems to be a piece of the puzzle out of place in resistant depression. Knowing the role of vitamin D in the nervous system so far as inflammation reduction and neuronal repair, there's a sensible mechanism at play as well.
Another interesting bit to the D replenishment story� in the past two years, four of my patients have developed high calcium with adequate D supplementation to bring the levels above 20 ng/ml. Three of them were found to be hyperparathyroid, and parathyroid tumors were found and later removed, resolving many of the original psychiatric complaints. The fourth patient is still undergoing a work-up but since a lump was palpated on the parathyroid, it is likely she has a tumor as well.
When I was in medical school, surgeons absolutely loved parathyroid cases because they were relatively rare. I don't know if four patients in two years is another anecdotal anomaly for me, but I do measure calcium along with vitamin D, and if the calcium pops above 10.2 with supplementation, I'm very quick to refer the patient back to the primary care doctor for further work-up. Having seen so many cases so recently, I wouldn't recommend supplementing a super-low D (particularly below 20, which is low enough that hyperparathyroidism can be masked by the low D level) aggressively without measuring calcium along with it. If you have normal levels (say 30 or above) moderate supplemention of 1000-2000 IU daily is probably fine, because if you had hyperparathyroidism, you would already know it, but keep measuring.
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