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2. A Link between Vitamin D and Frailty? The term “frailty” is becoming more and more popular in geriatric medicine. However, its definition is vague. The Oxford dictionary defined it by “the condition of being weak and delicate.” A more precise definition is given by Fried who defined frailty as “a biologic syndrome of decrease reserve and resistance to stressors that results from cumulative declines across multiple physiologic systems and causes vulnerability to adverse outcomes [68].” Criteria of the frail phenotype have been described in order to translate the above theoretical definition into clinical indicators [68]. These are as follows: unintentional weight loss, self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. According to these clinical criteria, 3 phenotypes have been identified: robust: 0 criteria; prefrail: between 1 and 2 criteria; frail: 3 or more criteria. The majority of these criteria are related to locomotion and physical strength. Thus, it looks readily conceivable that hypovitaminosis D may lead to frailty, through negative effects on muscle strength and/or function. The association between vitamin D status and frailty has been studied in a number of observational studies. Data from an observational study from Hirani et al. which included 1659 community-dwelling men, with a 10% prevalence of frailty, showed that low vitamin D levels were independently associated with frailty [69]. A similar association was found by Tajar et al. in another cohort of elderly men. Subjects with vitamin D levels <50 nmol/L had an odd ratio of 2,37 of being classified into the “frail” versus the “robust” phenotype [70]. Using data from the third National Health and Nutrition Survey (NHANES), Wilhelm-Leen et al. found an association between frailty and a low vitamin D status in both elderly men and women, with overall 4-fold increase in the odd ratio of frailty [71]. Vitamin D not only is associated with frailty but also appears to be associated with an increased risk to develop frailty over time in women. In a prospective study including elderly women (age > 69 years), nonfrail women at baseline but displaying a vitamin D level of less than 50 nmol/L hada higher risk of becoming frail during the 4.5 years of followup than women with a higher level of vitamin D [72]. In a study from patients with cardiac insufficiency, Boxer et al. found an association between low vitamin D levels and the frail phenotype. In particular, vitamin D levels and the result of the 6-minute walking test were correlated [73]. In cardiac diseases, this functional test is known to predict survival [74]. Thus, low vitamin D is hypothesized to link with mortality in this setting. A prospective study including 4000 individuals (1943 men and 2788 women, mean age: 70), followed up to 12 years, indeed found a link between lower levels of vitamin D, frailty, and mortality. An assessment of vitamin D status and the physical phenotype (robust/prefrail/frail) were performed at baseline [75]. Mortality was positively associated with frailty. Frail individuals with a low vitamin D level were at increased risk (hazard ratio of 2.98) of death during the follow-up compared to robust individuals with a high level of vitamin D. Thus, overall, a clear association between vitamin D level and frailty has been demonstrated. Furthermore, interplays between vitamin D status, frailty, and mortality appear plausible. Whether vitamin D supplementation in frail subjects may reduce mortality is challenging and needs to be investigated in the future.

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Summary

Fraility is defined differently as weak and delicate or decreased resistance to stressors, to translate these definitions different criteria are developed and further according to these criteria 3 phenotypes have been identified. Majority of criteria are related to locomotion and physical strength thus indicate the role of Hypovitaminosis D in fraility. Many studies have shown that deficiency of vitamin D results in fraility but there is need to study the effect of reducing the mortality by vitamin D supplementation.