Correction: Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study.

[This corrects the article DOI: 10.1371/journal.pone.0152441.].

Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study.

BACKGROUND: Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations. OBJECTIVES: To investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations. METHODS: Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25(OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer. RESULTS: Age-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12-0.90). CONCLUSIONS: 25(OH)D concentrations ≥40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined.

Commonly consumed protein foods contribute to nutrient intake, diet quality, and nutrient adequacy.

The amount of dietary protein needed to prevent deficiency in most individuals is defined in the United States and Canada by the Recommended Dietary Allowance and is currently set at 0.8 g protein · kg-1 · d-1 for adults. To meet this protein recommendation, the intake of a variety of protein food sources is advised. The goal of this article is to show that commonly consumed food sources of protein are more than just protein but also significant sources of essential nutrients. Commonly consumed sources of dietary protein frequently contribute substantially to intakes of nutrients such as calcium, vitamin D, potassium, dietary fiber, iron, and folate, which have been identified as nutrients of "concern" (i.e., intakes are often lower than recommended). Despite this, dietary recommendations to reduce intakes of saturated fat and solid fats may result in dietary guidance to reduce intakes of commonly consumed food sources of protein, in particular animal-based protein. We propose that following such dietary guidance would make it difficult to meet recommended intakes for a number of nutrients, at least without marked changes in dietary consumption patterns. These apparently conflicting pieces of dietary guidance are hard to reconcile; however, we view it as prudent to advise the intake of high-quality dietary protein to ensure adequate intakes of a number of nutrients, particularly nutrients of concern.

Quantifying the vitamin D economy.

Vitamin D enters the body through multiple routes and in a variety of chemical forms. Utilization varies with input, demand, and genetics. Vitamin D and its metabolites are carried in the blood on a Gc protein that has three principal alleles with differing binding affinities and ethnic prevalences. Three major metabolites are produced, which act via two routes, endocrine and autocrine/paracrine, and in two compartments, extracellular and intracellular. Metabolic consumption is influenced by physiological controls, noxious stimuli, and tissue demand. When administered as a supplement, varying dosing schedules produce major differences in serum metabolite profiles. To understand vitamin D's role in human physiology, it is necessary both to identify the foregoing entities, mechanisms, and pathways and, specifically, to quantify them. This review was performed to delineate the principal entities and transitions involved in the vitamin D economy, summarize the status of present knowledge of the applicable rates and masses, draw inferences about functions that are implicit in these quantifications, and point out implications for the determination of adequacy.

Making Sense of the Science of Sodium.

Despite the Institute of Medicine's commitment to base its nutrient intake recommendations in evidence, the 2004/2005 Dietary Reference Intakes for sodium were not supported by evidence, as the subsequent 2013 Institute of Medicine review admitted. In this review, I suggest an approach to setting nutrient intake requirements based in physiology. Briefly, the requirement of a given nutrient can best be said to be the intake that calls for the least adaptation or compensation by the intact organism. For sodium, evidence indicates that such an intake is typically between 3000 and 5000 mg/d.

Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D.

We examined the relationship between serum 25-hydroxyvitamin D (25[OH]D) and all-cause mortality. We searched biomedical databases for articles that assessed 2 or more categories of 25(OH)D from January 1, 1966, to January 15, 2013. We identified 32 studies and pooled the data. The hazard ratio for all-cause mortality comparing the lowest (0-9 nanograms per milliliter [ng/mL]) to the highest (> 30 ng/mL) category of 25(OH)D was 1.9 (95% confidence interval = 1.6, 2.2; P < .001). Serum 25(OH)D concentrations less than or equal to 30 ng/mL were associated with higher all-cause mortality than concentrations greater than 30 ng/mL (P < .01). Our findings agree with a National Academy of Sciences report, except the cutoff point for all-cause mortality reduction in this analysis was greater than 30 ng/mL rather than greater than 20 ng/mL.

Osteoporosis update: proceedings of the 2013 Santa Fe Bone Symposium.

The 2013 Santa Fe Bone Symposium included plenary sessions on new developments in the fields of osteoporosis and metabolic bone disease, oral presentations of abstracts, and faculty panel discussions of common clinical conundrums: scenarios of perplexing circumstances where treatment decisions are not clearly defined by current medical evidence and clinical practice guidelines. Controversial issues in the care of osteoporosis were reviewed and discussed by faculty and participants. This is a review of the proceedings of the Santa Fe Bone Symposium, constituting in its entirety an update of advances in the understanding of selected bone disease topics of interest and the implications for managing patients in clinical practice. Topics included the associations of diabetes and obesity with skeletal fragility, the complexities and pitfalls in assessing the benefits and potential adverse effects of nutrients for treatment of osteoporosis, uses of dual-energy X-ray absorptiometry beyond measurement of bone mineral density, challenges in the care of osteoporosis in the very elderly, new findings on the role of osteocytes in regulating bone remodeling, and current concepts on the use of bone turnover markers in managing patients with chronic kidney disease who are at high risk for fracture.

Guidelines for optimizing design and analysis of clinical studies of nutrient effects.

Presented here is a system to standardize clinical studies of nutrient effects, using nutrient-specific physiological criteria. These guidelines are based mainly on analysis of the typical sigmoid curve of biological response to nutrients and are intended for design, interpretation, and pooling of studies of nutrient effects. Five rules have been articulated for individual studies of nutrients, and six for systematic reviews and/or meta-analyses.

Quantifying the food sources of basal vitamin d input.

Cutaneous synthesis and traditional food sources do not fully account for unsupplemented vitamin D status. Non-traditional food sources may be an undiscovered input. In a cohort of 780 non-supplement-taking adults with a mean serum 25-hydroxyvitamin D [25(OH)D] of 33 (±14)ng/ml we assessed the relationship between vitamin D status and selected food sources. Serum 25(OH)D concentration was adjusted for season, UVB exposures, and body size. These adjusted values were then regressed against multiple food items and combinations. Whole milk cottage cheese, eggs, red meat, and total protein were positively associated with total 25(OH)D and/or 25(OH)D3 (P<0.05 for each), whereas fish and milk intake were not. The slope of the relationship was such that for every intake of 1serving/day, serum 25(OH)D rose by about 2ng/ml for eggs and 1ng/ml for meat and total protein. For every weekly serving of whole milk cottage cheese, serum 25(OH)D rose by about 1ng/ml. While some food sources were significant predictors of vitamin D status, their ability to explain inter-individual variability was limited. Supplementation will likely remain essential to improving vitamin D status on a population level. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

25-Hydroxyvitamin D in the range of 20 to 100 ng/mL and incidence of kidney stones.

OBJECTIVES: Increasing 25-hydroxyvitamin D serum levels can prevent a wide range of diseases. There is a concern about increasing kidney stone risk with vitamin D supplementation. We used GrassrootsHealth data to examine the relationship between vitamin D status and kidney stone incidence. METHODS: The study included 2012 participants followed prospectively for a median of 19 months. Thirteen individuals self-reported kidney stones during the study period. Multivariate logistic regression was applied to assess the association between vitamin D status and kidney stones. RESULTS: We found no statistically significant association between serum 25-hydroxyvitamin D and kidney stones (P = .42). Body mass index was significantly associated with kidney stone risk (odds ratio = 3.5; 95% confidence interval = 1.1, 11.3). CONCLUSIONS: We concluded that a serum 25-hydroxyvitamin D level of 20 to 100 nanograms per milliliter has no significant association with kidney stone incidence.

Quantifying the non-food sources of basal vitamin D input.

Unsupplemented vitamin D status is determined by cutaneous synthesis and food inputs; however, their relative magnitudes are largely unknown. In a cohort of 780 non-supplement-taking adults with a mean serum 25-hydroxyvitamin D [25(OH)D] of 33 (±14)ng/ml we assessed the relationship between serum 25(OH)D and non-food environmental variables. Serum 25(OH)D concentration was adjusted for seasonal influence (which removed 2% of the total variance) and these adjusted values were regressed against factors involved in cutaneous synthesis. Indoor tanning use, sun exposure, and percent of work performed outdoors were significantly positively associated and body mass index (BMI) was significantly negatively associated with 25(OH)D values (P<0.03 for each). Latitude, gender, and age were not significantly correlated (P>0.10). Season and non-food predictors together explained 13% of the total variance in serum 25(OH)D concentration. Non-traditional food sources need to be investigated as possible vitamin D inputs. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

25-Hydroxyvitamin D response to graded vitamin D3 supplementation among obese adults.

CONTEXT: Guidelines have suggested that obese adults need 2 to 3 times more vitamin D than lean adults to treat vitamin D deficiency, but few studies have evaluated the vitamin D dose response in obese subjects. OBJECTIVE: The purpose of this study was to characterize the pharmacokinetics of 25-hydroxyvitamin D [25(OH)D] response to 3 different doses of vitamin D3 (cholecalciferol) in a group of obese subjects and to quantify the 25(OH)D dose-response relationship. DESIGN, SETTING, INTERVENTION, PATIENTS: This was a randomized, single-blind study of 3 doses of oral vitamin D3 (1000, 5000, or 10,000 IU) given daily to 67 obese subjects for 21 weeks during the winter months. MAIN OUTCOME MEASURES: Serum 25(OH)D levels were measured at baseline and after vitamin D replacement, and 25(OH)D pharmacokinetic parameters were determined, fitting the 25(OH)D concentrations to an exponential model. RESULTS: Mean measured increments in 25(OH)D at week 21 were 12.4 ± 9.7 ng/mL in the 1000 IU/d group, 27.8 ± 10.2 ng/mL in the 5000 IU/d group, and 48.1 ± 19.6 ng/mL in the 10,000 IU/d group. Steady-state increments computed from the model were 20.6 ± 17.1, 35.2 ± 14.6, and 51.3 ± 22.0 ng/mL, respectively. There were no hypercalcuria or hypercalcemia events during the study. CONCLUSION: Our data show that in obese people, the 25(OH)D response to vitamin D3 is directly related to dose and body size with ∼2.5 IU/kg required for every unit increment in 25(OH)D (nanograms per milliliter).