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Vitamin D replacement increases blood levels but doesn't affect fatigue
Clinical Question
Is vitamin D effective to treat fatigue in healthy persons with low vitamin D levels?
Bottom line
A single large dose—100,000 units—of vitamin D increased vitamin D blood levels but did not affect fatigue to a clinically greater extent than placebo. 1b
Reference
Study design: Randomized controlled trial (double-blinded)
Funding: Foundation
Setting: Outpatient (any)
Synopsis
These investigators enrolled 120 patients (53% women, average age 29 years) with fatigue and a vitamin D deficiency. They excluded patients with known mental disorders, but did not specifically screen for anxiety or depression. The patients were at the low end of scores signifying fatigue: an average 24.9 and 23.3 of a possible 50 points in the treated and placebo groups, respectively (scores < 22 are considered normal). The investigators randomized patients, using concealed allocation, to receive a single dose of placebo or 100,000 units vitamin D (cholecalciferol). One month later the scores decreased (improved) an average 3.3 points in the treated group as compared with a 0.8-point average improvement in the placebo group. The difference in improvement, 2.5 points, is not clinically important—the minimum clinically important difference on the scoring system is 4 points.
Reviewer
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Comments
I have experienced opposite of this. Some patients improved after taking vit D3
This is a younger patient group than I usually treat.
The fatigue symptom was mild and I don't think very significant.
The outcome looked to be trending positive, but the whole magnitude was not really significant.
The way in which the Vit D was given makes me think it might have implications on how we replenish people when we know that they have low Vit D levels.
Is low Vit D associated with fatigue?
This study may very well bear repeating.
bad poem
It's a common clinical scenario so info is useful as there is no best practice yet for vit D replacement
Giving many days worth of D3 all at once results in less act
Clinically, I have seen D3 given *daily* improve fatigue and mood in people likely to have low levels of vitamin D. (People likely to have low levels of vitamin D are those who don't go outside, who go outside with skin covered either by clothes or sunscreen, who have dark skin, who have a high BMI, who are over age 50, or who have conditions like osteopenia / osteoporosis, high PTH, etc. etc.)
Giving many days worth of vitamin D all at once would cause a peak of the (mostly inactive) 25(OH)D, with the result that more 25(OH)D gets broken down and excreted rather than being activated to 1,25(OH)D than is the case when D3 is given as daily doses. There is considerable inter-individual variation in this, as you would expect given the multiple polymorphisms affecting vitamin D metabolism and vitamin D receptor function.
For example, Saleh et al, https://www.degruyter.com/view/j/cclm.ahead-of-print/cclm-2016-1129/ccl… - "Administration of a single high dose of vitamin D3 leads to a significant increase in concentrations of 25(OH)D3, 24,25(OH)2D3, 3-epi-25(OH)D3 and 1,25(OH)2D3; induction of the catabolic pathway predominates over the production of 1,25(OH)2D3. Due to the high inter-individual variation in the 25(OH)D3 response to supplementation, any given dose of vitamin D is unlikely to achieve optimal vitamin D status in all treated individuals."
The title of the POEM should not be, "Vitamin D replacement increases blood levels but doesn't affect fatigue," it should be "One large dose of D3 given once doesn't affect fatigue a month later."
Good poem
clinical significance?
What is your criteria for clinical significance? What source are you using that informs that 2.5 is not a clinical significance? The authors report a statistical significance in the article..
The short time of the treatmen (one month) and the lack of screening for depression means this study is fairly weak.