On February 16, 2017, the British Medical Journal published the largest meta-analysis to date, finding that vitamin D was effective in preventing colds and flu. Its lead author, Professor Adrin Martineau, took on the burden of supervising this project. They found vitamin D is more effective than flu shots in reducing the flu. (However, the flu can be deadly, so it is important to continue receiving your flu shots to double your protection). The paper is very well written.
Martineau Adrian R, Jolliffe David A, Hooper Richard L, Greenberg Lauren, Aloia John F, Bergman Peter et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ 2017; 356 :i6583.
The meta-analysis included 25 randomized controlled trials, some of which used inadequate doses of vitamin D and some studies that used “stoss” or bolus dosing, where they provide 100,000 to 300,000 IU every month or two. As Professor Reinhold Vieth pointed out several years ago, stoss dosing is problematic because it causes 25(OH)D levels to rapidly rise, which induces the 24-hydroxylase to degrade 25(OH)D. This enzyme degrades 1,25(OH)2D as well, causing intracellular vitamin D deficiency.
The take away point is to take vitamin D daily, or better yet, to briefly (5 to 20 minutes) sunbathe (weather permitting) when your shadow is shorter than you are.
Eleven years is a long time; this was when (2006) we first hypothesized that vitamin D supplements would reduce the incidence of colds and flu (free access).
Within a month of our paper, a group wrote in with what appeared to be definitive proof that I was correct (also open access). They reported that 2,000 IU/day virtually prevented the flu and colds.
However, that report proved too good to be true, because dozens of studies followed with either minimal or no effects. To date, 5 meta-analyses have evaluated whether vitamin D prevented colds and flu, with two studies supporting this hypothesis and three presenting negative findings. So, let’s look a little closer at what the BMJ reported this morning.
The researchers analyzed 25 randomized controlled trials with about 11,000 subjects. The doses ranged from 200 IU/day to 4,000 IU/day, excluding the studies that used bolus dosing (the trials using bolus dosing found no treatment effects). I could not find any trials that used 5,000 IU/day or higher.
However, despite the relatively low doses used, the researchers found significant treatment effects in subjects with baseline 25(OH)D < 10 ng/ml (adjusted odds ratio 0.58, 0.40 to 0.82, number needed to treat=8, 5 to 21; 538 participants in 14 studies; significance within subgroup P=0.002). In another subgroup analysis, they also found the use of daily or weekly vitamin D protected against acute respiratory tract infection among participants with higher baseline 25(OH)D > 10 ng/ml (adjusted odds ratio 0.75, 0.60 to 0.95; NNT=15, 9 to 86; 1603 participants in six studies; within subgroup P=0.02).
What is needed is a two year-long study, which obtains baseline and final 25(OH)D levels, a control arm whose subjects have 25(OH)D < 20 ng/ml who are treated with 400 to 800 IU/day, depending on age. It is unethical to find vitamin D deficiency in a subject and not treat it. The treatment group should be given at lease 100-150 IU/kg/day of vitamin D3. Until that study is done, we will not know the power of vitamin D to prevent colds and flu.
Fourteen years ago, when I started taking 5,000 IU/day, I was amazed how infrequently I got a cold or flu. However, about 4 years later I developed the flu; six years after this, I got a cold and two years ago, I developed the flu again (despite getting a flu shot, which I do every year). The explanation is that vitamin D levels are only one of the factors that affect upper respiratory infections. Other factors include the infectivity of the pathogen, the lethality of the pathogen, the infecting dose of pathogen one obtains and whether the infectious agent has a lipoprotein coat. Cathelicidin, the naturally occurring antimicrobial peptide (AMP) upregulated by 1,25(OH)2D, works by punching a hole in the lipoprotein coat.
How do AMPs like cathelicidin work? AMPs protect mucosal epithelial surfaces by creating a hostile antimicrobial shield. The epithelia secrete them constitutively into the thin layer of fluid that lies above the apical surface of the epithelium but below the viscous mucous layer. To effectively access the epithelium, a microbe, such as influenza, must first penetrate the mucous barrier and then survive damage inflicted by the AMPs present in the fluid that is in immediate contact with the epithelial surface. Should this constitutive barrier be breached, the binding of microbes to the epithelium and/or local tissue injury rapidly provokes the expression of high concentrations of specific inducible AMPs such as human beta-defensin 2 and cathelicidin, that provide a “back-up” antimicrobial shield. These inducible AMPs also act as chemo-attractants for macrophages and neutrophils that are present in the immediate vicinity of the site of the microbial breach. In addition, cathelicidin plays a role in epithelial repair by triggering epithelial growth and angiogenesis
So, the lesson is stay on 5,000 to 10,000 IU/day unless you can sunbathe, which is a better choice. Also, check your 25(OH)D level at least once a year, preferably in the late winter. [/private]