Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study

Canadian Medical Association Journal (Impact Factor: 5.81). 11/2012; 184(18). DOI: 10.1503/cmaj.120233
Source: PubMed

ABSTRACT BACKGROUND:Low levels of 25(OH) vitamin D are associated with various age-related diseases and mortality, but causality has not been determined. We investigated vitamin D levels in the offspring of nonagenarians who had at least one nonagenarian sibling; these offspring have a lower prevalence of age-related diseases and a higher propensity to reach old age compared with their partners. METHODS:We assessed anthropometric characteristics, 25(OH) vitamin D levels, parathyroid hormone levels, dietary vitamin D intake and single nucleotide polymorphisms (SNPs) associated with vitamin D levels. We included offspring (n = 1038) of nonagenarians who had at least one nonagenarian sibling, and the offsprings' partners (n = 461; controls) from the Leiden Longevity Study. We included age, sex, body mass index, month during which blood sampling was performed, dietary and supplemental vitamin D intake, and creatinine levels as possible confounding factors. RESULTS:The offspring had significantly lower levels of vitamin D (64.3 nmol/L) compared with controls (68.4 nmol/L; p = 0.002), independent of possible confounding factors. There was no difference in the levels of parathyroid hormone between groups. Compared with controls, the offspring had a lower frequency of a genetic variant in the CYP2R1 gene (rs2060793) (p = 0.04). The difference in vitamin D levels between offspring and controls persisted over the 2 most prevalent genotypes of this SNP. INTERPRETATION:Compared with controls, the offspring of nonagenarians who had at least one nonagenarian sibling had a reduced frequency of a common variant in the CYP2R1 gene, which predisposes people to high vitamin D levels; they also had lower levels of vitamin D that persisted over the 2 most prevalent genotypes. These results cast doubt on the causal nature of previously reported associations between low levels of vitamin D and age-related diseases and mortality.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Public health authorities around the world recommend widely variable supplementation strategies for adults, whereas several professional organizations, including The Endocrine Society, recommend higher supplementation. Methods: We analyzed published randomized controlled clinical trials to define the optimal intake or vitamin D status for bone and extraskeletal health. Conclusions: The extraskeletal effects of vitamin D are plausible as based on preclinical data and observational studies. However, apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly, causality remains yet unproven in randomized controlled trials (RCTs). The greatest risk for cancer, infections, cardiovascular and metabolic diseases is associated with 25-hydroxyvitamin D (25OHD) levels below 20 ng/mL. There is ample evidence from RCTs that calcium and bone homeostasis, estimated from serum 1,25-dihydroxyvitamin D and PTH, calcium absorption, or bone mass, can be normalized by 25OHD levels above 20 ng/mL. Moreover, vitamin D supplementation (800 IU/d) in combination with calcium can reduce fracture incidence by about 20%. Such a dose will bring serum levels of 25OHD above 20 ng/mL in nearly all postmenopausal women. Based on calculations of the metabolic clearance of 25OHD, a daily intake of 500-700 IU of vitamin D3 is sufficient to maintain serum 25OHD levels of 20 ng/mL. Therefore, the recommendations for a daily intake of 1500-2000 IU/d or serum 25OHD levels of 30 ng or higher for all adults or elderly subjects, as suggested by The Endocrine Society Task Force, are premature. Fortunately, ongoing RCTs will help to guide us to solve this important public health question.
    The Journal of Clinical Endocrinology and Metabolism 08/2013; 98(8):E1283-304. DOI:10.1210/jc.2013-1195 · 6.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionInflammation is believed to be a contributing factor to many chronic diseases. The influence of vitamin D deficiency on inflammation is being explored but studies have not demonstrated a causative effect.MethodsLow serum 25(OH)D is also found in healthy persons exposed to adequate sunlight. Despite increased vitamin D supplementation inflammatory diseases are increasing. The current method of determining vitamin D status may be at fault. The level of 25(OH)D does not always reflect the level of 1,25(OH)2D. Assessment of both metabolites often reveals elevated 1,25(OH)2D, indicating abnormal vitamin D endocrine function.FindingsThis article reviews vitamin D's influence on the immune system, examines the myths regarding vitamin D photosynthesis, discusses ways to accurately assess vitamin D status, describes the risks of supplementation, explains the effect of persistent infection on vitamin D metabolism and presents a novel immunotherapy which provides evidence of an infection connection to inflammation.ConclusionSome authorities now believe that low 25(OH)D is a consequence of chronic inflammation rather than the cause. Research points to a bacterial etiology pathogenesis for an inflammatory disease process which results in high 1,25(OH)2D and low 25(OH)D. Immunotherapy, directed at eradicating persistent intracellular pathogens, corrects dysregulated vitamin D metabolism and resolves inflammatory symptoms.
    Inflammation Research 07/2014; 63(10). DOI:10.1007/s00011-014-0755-z · 2.14 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this population-based prospective observational study was to examine the relationship between serum levels of 25-hydroxyvitamin D (25OHD) and fracture risk in a cohort of 1662 community-dwelling men aged 70–97 years followed for a mean of 4.3 years. Data about mobility, muscle strength, balance, medication use, cognition, medical history, lifestyle factors, renal function and serum 25OHD were collected at baseline. Data on radiologically verified fractures were collected every 4 months. The relationship between fractures and serum 25OHD levels was analyzed using Cox's proportional hazard regression.We accounted for bone mineral density, falls, physical activity, sun exposure, season of blood draw, in addition to anthropometric and lifestyle factors, medical history, muscle strength, balance, medication and supplement use.There were 123 first incident fragility fractures. The relationship between baseline 25OHD and fracture risk was U-shaped, with increased fracture risk in men with either low or high serum 25OHD levels. In multivariate analysis, the risk of fracture was greatest in men with 25OHD levels in the lowest quintile (25OHD ≤ 36nmol/L; hazard ratio (HR) = 3.5 (95% confidence interval (CI): 1.7–7.0) and in men in the highest quintile (25OHD >72nmol/L; HR = 2.7, 95% CI: 1.4–5.4) compared to men in the 4th quintile (25OHD ≥60 to ≤72nmol/L). These associations were not explained by lower BMD, increased physical activity, falls' risk or other lifestyle or anthropomorphic factors.In community-dwelling older men, there appears to be a healthy target range for serum 25OHD concentrations. Thus, serum 25OHD levels too high and too low may be harmful in regards to fracture risk. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2014; 29(9). DOI:10.1002/jbmr.2230 · 6.04 Impact Factor


Available from
Jun 3, 2014