Vitamin D predicts good health and long life in seniors, review of 20 cohort studies – Oct 2019

Vitamin D as a Biomarker of Ill Health among the Over-50s: A Systematic Review of Cohort Studies

Nutrients 2019, 11(10), 2384; https://doi.org/10.3390/nu11102384

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Silvia Caristia 1,Nicoletta Filigheddu 1,Francesco Barone-Adesi 1,Andrea Sarro 1,Tommaso Testa 1,Corrado Magnani 1,Gianluca Aimaretti 1,Fabrizio Faggiano 1,2 andPaolo Marzullo 1,3,*
1 Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
2 Epidemiology Centre of Local Health Unit of Vercelli, 12100 Vercelli, Italy
3 I.R.C.C.S. Istituto Auxologico Italiano, Piancavallo, 28921 Verbania, Italy

Background: The association between circulating levels of vitamin D and the incidence of chronic diseases is known. The identification of vitamin D as a biomarker of physiological/pathological ageing could contribute to expanding current knowledge of its involvement in healthy ageing.

Methods: According to PRISMA guidelines, a systematic review was conducted on cohorts studying the role of 25OH-Vitamin D [25(OH)D] and 1,25(OH)2-Vitamin D 1,25(OH)2D concentrations as biomarkers of healthy ageing. We consulted MedLine, Scopus, and Web of Science to search for studies on the association between vitamin D status in populations of originally healthy adults, and outcomes of longevity, illness, and physical and cognitive functionality. The quality of the studies was assessed using the Newcastle Ottawa scale.

Results: Twenty cohorts from 24 articles were selected for this review. Inverse associations were found between low 25(OH)D levels and all-cause mortality, respiratory and cardiovascular events, as well as markers relating to hip and non-vertebral fractures. Associations between 1,25(OH)2D and healthy ageing outcomes gave similar results, although of lower clinical significance.

Conclusions: This systematic review pinpoints peculiar aspects of vitamin D as a multidimensional predictor of ill health in the ageing process. Further well-designed controlled trials to investigate whether vitamin D supplement results in superior outcomes are warranted in the future.

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Cardiovascular, Coronary, and Cardiometabolic Events
These events were observed in five articles reporting on negative associations between 25(OH)D and CV or coronary events. The risk of CV events increased with declining vitamin D levels at baseline. Liu et al. [69] reported a 2-time higher risk of death from heart failure for the lowest tertile in comparison with the highest one, while Brondum-Jacobsen et al. [74] showed a >50% higher risk of the lowest 25(OH)D category, which was up to 110% for fatal events. In three studies, evidence of a protective effect for the highest vitamin D levels was found [56,59,68], with a nearly 50% risk reduction between the highest and lowest quartile [56] and with a HR = 0.71 for every increase of a SD in vitamin D level [59]. Finally, 25(OH)D was not associated with CV mortality [63] nor with nonfatal CV events [74]. Al-Khalidi et al. showed an inverse association with cardiometabolic causes of mortality (i.e., heart diseases, cerebrovascular diseases, and diabetes mellitus), concluding that total levels of serum vitamin D <30 nmol/L were predictive of high lifetime risk of cardiovascular and metabolic death, even without weight loss or BMI modifications [77]. By contrast, 25(OH)D was not associated with CV mortality [63], non-fatal CV events [74], or insulin resistance [70].

Conclusions
Conclusively, 25(OH)D status acts as a worthy biomarker to predict all-cause mortality, pulmonary events, and lung function, cardiovascular/coronary events, hip fractures, early and/or premature death, and sarcopenia incidence. Conversely, no association was found with the risk of falls, as well as with bone mineral density, cognitive function, cardiometabolic, and cancer events in adult populations who were apparently healthy at baseline. As far as 1,25(OH)2D is concerned, its associations with all-cause mortality and respiratory events do not seem to be of relevant clinical value.
There is a clear limited scientific evidence on the role of vitamin D metabolites in the multidimensional process of ageing, since the studies analyzed by our review deal with a limited spectrum of markers of healthy ageing, and markers such as social participation, social function, as well as subjective dimensions related to self-perception of own status and resources [95-98] were missing. For this reason, we cannot draw definitive conclusions on vitamin D as a reliable predictor of the healthy ageing process for all dimensions herein investigated. Nevertheless, we are inclined to consider the robust results on relevant markers such as longevity and incidence of disease, as a strong support to consider vitamin D as a multidimensional predictor of ill health in the ageing process. Further well-designed controlled trials to investigate whether vitamin D supplement results in superior outcomes are warranted in the future.