I realize that when I write for a journal that most of my readers cannot access my writing. This month the British Journal of Nutrition invited me to write an article; it is below. To put the article into context, my long-time readers will remember the excitement back in 2005 when I discovered that vitamin D appeared to prevent influenza.
The difference between a prophet and a madman
Edgar Hope-Simpson was a self-taught young genius epidemiologist who turned into a gracious old man obsessed with his hypothesized ‘seasonal stimulus’ for epidemic influenza. He was the scientist who discovered the aetiology of shingles, but he was also the man who seemingly wasted the last 20 years of his life trying to untangle the manifold mysteries of influenza. Among his last written words, he cordially pleaded with the giants of influenzology, ‘it might be rewarding if persons, who are in a position to do so, would look more closely at the operative mechanisms that are causing such seasonal behaviour’. He died bereft of any recognition of his discovery that epidemiology of influenza is controlled by an unknown ‘seasonal stimulus’, whose character is dominated by a distinct aversion to sunlight.
Edgar Hope-Simpson had the rare gift of understanding the difference between fact and theory. For example, he knew that the statement, ‘children with rickets have frequent pneumonia because their rib cages are too weak to cough effectively’, contains one fact and one theory. Similarly, ‘influenza is more common in the winter due to overcrowding’, and ‘influenza is spread from person to person via respiratory droplets’, and ‘influenza spreads so rapidly because it is highly contagious’. He knew all these statements contain one fact and one theory and by distinguishing fact from theory, he wrote what is still the best book on influenza.
Indeed, his book led directly to two influenza publications from our group, the last one of which we used vitamin D to explain nine major conundrums of influenza. We predicted that vitamin D will both prevent and treat influenza, once modern medicine learns proper maintenance dosage (25mcg (1,000 IU/10 kg per day), not unlike the dosing of thyroxin.
The mechanism of action of vitamin D in preventing and treating various infections, a mechanism that led Science News to characterize vitamin D as the ‘the antibiotic vitamin’ has become evident only very recently. Both epithelial cells and macrophages increase expression of the antimicrobial cathelicidin upon exposure to microbes, an expression that is dependent upon the presence of vitamin D. Pathogenic microbes, much like the commensals that inhabit the upper airway, stimulate the production of a hydroxylase that converts 25(OH)D to 1,25(OH)2D, a seco-steroid hormone. This, in turn, activates a suite of genes involved in defense.
In the epidermis, vitamin D induces additional PAMP (pathogen associated molecular pattern) receptors, enabling keratinocytes to recognize and respond to microbes. Thus, vitamin D appears to both enhance the local capacity of the epithelium to produce endogenous antibiotics and – at the same time – dampen certain arms of the adaptive immune response, especially those responsible for the signs and symptoms of acute inflammation.
All this leads to the recent paper by Berry et al. in this edition of the British Journal of Nutrition, the first paper to take season, lifestyle and health factors into account while associating 25(OH)D levels and self-reports of respiratory infections. The effect size was large, about a 10% less risk of infection for every 4 ng/ml increase in 25(OH)D. Summer-time levels never reached 40 ng/ml the level that some feel is the lower limit of health.
The authors remain hesitant, for the reasons they list, to recommend vitamin D for asthmatic children. In the authors’ discussion of Ginde et al. they failed to note that the association between low vitamin D and infection was about four times stronger in asthmatic children than in non-asthmatic ones. Furthermore, while asthmatic numbers described by Urashima et al were small, they were highly significant, finding that 1,200 IU/day of vitamin D effectively prevented exacerbations in asthmatic children (P<0·006) compared with placebo.
As a practitioner, I believe the medical community should consider vitamin D deficiency as a ‘known health hazard’, and aggressively treat it – in asthmatic individuals as well. Although anecdotal, I have observed high doses of vitamin D (5,000 IU/10 kg per day for 6 months then reduce to maintenance) seemingly ‘cure’ some childhood asthma in about 6 months. I hesitate to mention this but cannot find ethical reasons that allow me to exclude it from my comments.
Finally, to be sure, the study by Berry et al. speaks only of the respiratory system, yet antimicrobial effects of vitamin D may be more generalized. Recently, researchers in Tennessee wanted to know if vitamin D levels were associated with overall mortality in the intensive care unit (ICU). They found patients were almost twice as likely to die during an ICU stay if they had vitamin D deficiency (<20 ng/ml).
Respiratory infections are but one failure of the immune system that lead children into the ICU. Meningitis is another, a grim wintertime scythe that should be treated not only with conventional antimicrobials, but also (in my opinion) with pharmacological doses of vitamin D (10,000 IU/10 kg per day for several days). And, should any promising observer note an association between meningitis and a ‘seasonal stimulus’, and then suffer the scorn of their colleagues, remember Dr. Edgar Hope-Simpson and remember also that time alone distinguishes a prophet from a madman.
Dr. Cannell is founder and principal of the educational organization, the Vitamin D Council. In addition, he receives royalties from Purity Products on the sale of his ‘Advanced Vitamin D Formula’.