Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Schöttker, Ben; Jorde, Rolf; Peasey, Anne; Thorand, Barbara; Jansen, Eugène; Groot, Lisette C. P. G. M. de; Streppel, Martinette T; Gardiner, J. Stanley; Ordóñez‐Mena, José M.; Perna, Laura; Wilsgaard, Tom; Rathmann, Wolfgang; Feskens, Edith J. M.; Kampman, Ellen; Siganos, Galatios; Njølstad, Inger; Mathiesen, Ellisiv B.; Kubínová, Růžena; Pająk, Andrzej; Topór-Mądry, Roman; Tamošiūnas, Abdonas; Hughes, Maria; Kee, Frank; Bobák, Martin; Trichopoulou, Antonia; Boffetta, Paolo; Brenner, Hermann

doi:10.1136/bmj.g3656

Cited by 380 publications

(327 citation statements)

References 38 publications

(50 reference statements)

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“…However, it is uncertain how much these differences are related to different ultraviolet B exposure, vitamin D consumption in the diet, and vitamin D fortification habits in the countries or are just artefacts of the different 25(OH)D assays employed. 2 Surprisingly, a recent meta-analysis confirmed that population means of 25(OH)D concentrations are higher in northern than in southern Europe, as it was also reported by Seneca study, a previous important European cohort study. 3 The Authors of this latter study mainly suspected country differences in vitamin D fortification of foods, such as margarine, as possible causes of the large regional differences.…”

Section: Vitamin D Insufficiency and Deficiencymentioning

confidence: 58%

“…2 These data evidence that it is difficult to identify cut-off values for vitamin D deficiency, namely for 25(OH)D variations by geographic region, sex, and season, factors that might need to be taken into account (Table 1). The American Institute of Medicine (IOM) recommends to distinguish a level of insufficiency [defined as 30-50 nmol/L or 16-25 ng/mL of 25(OH)D] and another of deficiency identified by 25(OH)D levels lower than 30 nmol/L (or <16 ng/mL).…”

Section: Potential Role Of Vitamin D In Prevention Of Skeletal and Exmentioning

confidence: 99%

“…16 To date, the evidence is not yet sufficient to recommend vitamin D3 supplementation for subjects with vitamin D insufficiency (defined as 30-50 nmol/L 25(OH)D) however it helps to understand that subjects with vitamin D deficiency (<30 nmol/L 25(OH)D) could profit from vitamin D3 supplementation by maintaining bone health and reduction in fracture risk. 2 …”

Section: Vitamin D and Bone Fracturesmentioning

confidence: 99%

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Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Montagnani

Nardi²,

Cercignani

et al. 2015

Ital J Med

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Vitamin D and calcium are essential for bone health. An adequate calcium-phosphorus product determines a high quality mineralization long lifetime. In older people, both calcium and vitamin D levels may be lower causing osteomalacia and/or osteoporosis with a higher risk of fracture. Epidemiological data have clearly associated serum vitamin D lower levels (deficiency) with bone fracture in older people, however, not univocal data exist in regard to a beneficial effect of vitamin D supplementation in general population. Although not systematic, the present review aims to make a narrative synthesis of the most recent published data on vitamin D effect not only on bone, classical target associated with vitamin D studies, but namely on extraskeletal diseases. In fact, recently, there has been an increasing interest on this latter issue with surprising findings. Vitamin D, and in particular its deficiency, seems to have a role in pathophysiological pathways in several diseases involving cardiovascular, central nervous system and neoplastic process. On the other hand, vitamin D supplementation may modify the outcome of a wide range of illnesses. Up to date the data are conflicting mainly because of difficulty to establish a consensus on the threshold of vitamin D deficit. The US Institute of Medicine recommends to distinguish a level of insufficiency [defined as 30-50 nmol/L or 16-25 ng/mL of 25(OH)D] and another of deficiency identified by 25(OH)D levels lower than 30 nmol/L (or <16 ng/mL). This latter level is considered a minimum level necessary in older adults to minimize the risk of falls, fracture and probably to have some effects of vitamin D supplementation in extraskeletal diseases. Although there are no absolute certainties in such issue, the most recent data suggest that vitamin D deficiency, and its supplementation, may play an important role in a wide range of diseases other than in bone metabolic diseases in older but not in general population. For such reason a widespread measurement of vitamin D levels in general population, and not only in older, seems to be inappropriate and it could induce an overuse of vitamin D supplementation in situations in which its efficacy and cost-effectiveness have not been proven.

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Section: Vitamin D Insufficiency and Deficiencymentioning

confidence: 58%

Section: Potential Role Of Vitamin D In Prevention Of Skeletal and Exmentioning

confidence: 99%

Section: Vitamin D and Bone Fracturesmentioning

confidence: 99%

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Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Montagnani

Nardi²,

Cercignani

et al. 2015

Ital J Med

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“…Whereas the link between vitamin D deficiency and allcause mortality is well-established [38][39][40][41], the current epidemiological evidence linking endogenous total and free testosterone concentrations to mortality risk among men remains inconclusive. While total testosterone was mostly negatively related to mortality [13,14,16,20,42] with one study reporting a non-significant relationship [22], free testosterone was positively [22] or negatively [5] related to mortality andlimited evidence suggests that SHBG may not be related [22] to mortality.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and biomarkers of sex steroid hormones are non-linearly and inversely related to all-cause mortality: results from NHANES III

Beydoun¹,

Eid²,

Jeng³

et al. 2015

Horm Stud

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Background: In men, hypovitaminosis D as well as high and low testosterone levels have been linked to adverse events, including death. A biological interaction has been previously suggested between vitamin D and androgens. In a cohort study using Third National Health and Nutrition Examination Survey data, we simultaneously investigated circulating vitamin D and biomarkers of sex steroid hormones as predictors of all-cause mortality. Methods: Age-adjusted and fully-adjusted Cox regression models were constructed to estimate hazard ratios (HR) and their 95% confidence intervals (CI). Whereas the vitamin D sufficient group (25(OH)D 3 ≥30 ng/ml) was selected as a referent, biomarkers of sex steroid hormones (testosterone, estradiol, SHBG) were defined as Loge-transformed continuous variables. Results: Of 1,472 men with a mean age of 42.1 years at baseline, 382 died over a median of 192 months of follow-up. Estradiol levels were significantly higher among vitamin D deficient compared to vitamin D sufficient men and sex hormone binding globulin level was significantly higher in vitamin D sufficient compared to vitamin D insufficient or deficient groups. An inverse non-linear relationship was observed between all-cause mortality rate and levels of testosterone, estradiol and vitamin D, in fully-adjusted models. There were no significant interaction effects between vitamin D and sex steroid hormones in relation to all-cause mortality rate. Conclusions: Vitamin D and sex steroid hormones, but not sex hormone binding globulin, may be inversely and non-linearly related to all-cause mortality among adult men, after adjustment for baseline demographic, socioeconomic, lifestyle and clinical characteristics.

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“…This led the Scientific Advisory Committee on Nutrition to recommend a daily vitamin D intake of 10 µg for all adults within the UK (1) . CVD is one of the main causes of morbidity and mortality in the world and there is mounting evidence indicating an association between suboptimal vitamin D status and increased risk of CVD (3)(4)(5)(6) and all-cause mortality (7)(8)(9) . However, few prospective cohort studies have analysed the relationship between vitamin D intake and CVD risk and allcause mortality.…”

mentioning

confidence: 99%

Vitamin D intake and risk of CVD and all-cause mortality: evidence from the Caerphilly Prospective Cohort Study

Guo

Cockcroft

Elwood

et al. 2017

Public Health Nutr.

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Objective: Prospective data on the associations between vitamin D intake and risk of CVD and all-cause mortality are limited and inconclusive. The aim of the present study was to investigate the associations between vitamin D intake and CVD risk and all-cause mortality in the Caerphilly Prospective Cohort Study. Design: The associations of vitamin D intake with CVD risk markers were examined cross-sectionally at baseline and longitudinally at 5-year, 10-year and >20-year follow-ups. In addition, the predictive value of vitamin D intake for CVD events and all-cause mortality after >20 years of follow-up was examined. Logistic regression and general linear regression were used for data analysis. Setting: Participants in the UK. Subjects: Men (n 452) who were free from CVD and type 2 diabetes at recruitment. Results: Higher vitamin D intake was associated with increased HDL cholesterol (P = 0·003) and pulse pressure (P = 0·04) and decreased total cholesterol:HDL cholesterol (P = 0·008) cross-sectionally at baseline, but the associations were lost during follow-up. Furthermore, higher vitamin D intake was associated with decreased concentration of plasma TAG at baseline (P = 0·01) and at the 5-year (P = 0·01), but not the 10-year examination. After >20 years of follow-up, vitamin D was not associated with stroke (n 72), myocardial infarctions (n 142), heart failure (n 43) or all-cause mortality (n 281), but was positively associated with increased diastolic blood pressure (P = 0·03). Conclusions: The study supports associations of higher vitamin D intake with lower fasting plasma TAG and higher diastolic blood pressure. KeywordsVitamin D CVD All-cause mortality Caerphilly Prospective Cohort Study TAG Recently, the UK Scientific Advisory Committee on Nutrition (1) reported that 22-24 % of individuals aged 19-64 years and 17-24 % of those aged ≥65 years in the UK were vitamin D deficient (plasma 25-hydroxycholecalciferol <25 nmol/l).People generally obtain vitamin D from synthesis in the skin due to sunlight UV radiation and/or foods. However, a number of relatively recent lifestyle changes (increased working indoors, sunscreen use), personal characteristics (ageing, skin pigmentation) and geographic reasons (latitude) limit the ability to synthesise adequate vitamin D from sunlight (2) . As a result, vitamin D intake from foods has become more important than previously. This led the Scientific Advisory Committee on Nutrition to recommend a daily vitamin D intake of 10 µg for all adults within the UK (1) . CVD is one of the main causes of morbidity and mortality in the world and there is mounting evidence indicating an association between suboptimal vitamin D status and increased risk of CVD (3)(4)(5)(6) and all-cause mortality (7)(8)(9) . However, few prospective cohort studies have analysed the relationship between vitamin D intake and CVD risk and allcause mortality. In a 10-year cohort of 361 men and 394 women (10) , lower vitamin D intake was associated with an increased risk of stroke, but not myocardial...

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Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Cited by 380 publications

References 38 publications

Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Potential role of vitamin D in prevention of skeletal and extraskeletal diseases in older people

Vitamin D and biomarkers of sex steroid hormones are non-linearly and inversely related to all-cause mortality: results from NHANES III

Vitamin D intake and risk of CVD and all-cause mortality: evidence from the Caerphilly Prospective Cohort Study

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