Are Hill's criteria for causality satisfied for vitamin D and periodontal disease?

There is mounting evidence that periodontal disease (PD) is linked to low serum 25-hydroxyvitamin D [25(OH)D] concentrations in addition to recognized risk factors like diet and smoking. This paper reviews this evidence using Hill's criteria for causality in a biological system. Evidence for strength of association, consistency, cohesion and 'dose-effects' [biological 'gradients'] include strong inverse correlations between serum 25(OH) and PD cross-sectionally and that PD is consistently more prevalent in darker vs. lighter skinned people and increases at higher latitudes with analogy for gingivitis and for disorders associated with PD whose risks also increase with hypovitaminosis D. Evidence for plausibility includes that vitamin D increases calcium absorption and protects bone strength; induces formation of cathelicidin and other defensins that combat bacterial infection; reduces tissue production of destructive matrix metalloproteinases actively associated with PD and that prevalence of PD varies with common vitamin D receptor polymorphisms. Experimental evidence from limited supplementation studies [using calcium and vitamin D] shows that supplementation reduces tooth loss. Thus, existing evidence for hypovitaminosis D as a risk factor for PD to date meets Hill's criteria for causality in a biological system. Further experimental evidence for effectiveness and temporality, preferably from randomized controlled trials of vitamin D supplementation [adjusting for other PD risk factors including diet and smoking to reduce confounding] are necessary to confirm causality. If confirmed, dentists and periodontists could perform a valuable service to their patients by discussing the importance of adequate vitamin D status and how to avoid deficiency.