Jean-Claude Souberbielle

Determinants of vitamin D status in Caucasian adults: influence of sun exposure, dietary intake, sociodemographic, lifestyle, anthropometric, and genetic factors.

Very few studies have investigated the determinants of serum vitamin D levels using a set of variables that include simultaneously sun exposure, phototype, dietary intake, sociodemographics, anthropometric, lifestyle data, and genetic polymorphisms. Our objective was to investigate the associations between all these parameters and vitamin D status in a large sample of French adults. This cross-sectional survey was based on 1,828 middle-aged Caucasian adults from the SU.VI.MAX (SUpplémentation en VItamines et Minéraux AntioXydants) study. Plasma 25-hydroxyvitamin D (25OHD) concentration was lower among women (P<0.0001), older subjects (P=0.04), obese/underweight (P<0.0001), those living at higher latitudes (P<0.0001), those whose blood draw occurred in early spring (P<0.0001), less physically active (P<0.0001), with low sun exposure (P<0.0001), and with no-to-low alcohol intake (P=0.0001). Mutant GC rs4588 and rs7041 single nucleotide polymorphisms were associated with lower and higher 25OHD concentrations, respectively (P<0.0001). Dietary intake was not a major determinant of vitamin D status (P=0.7). This study provides an overall picture of determinants of vitamin D status. Several modifiable factors were identified, such as daily-life moderate sun exposure, physical activity, and normal-weight maintenance, which should be targeted by public health policies in order to improve vitamin D status in the general population, while avoiding active/intensive sun exposure, in line with recommendations for skin cancer prevention.

Association of nutrition in early life with body fat and serum leptin at adult age.

Background:There is overwhelming evidence that experiences during early life could have long-term health consequences. However, the role of early nutrition in programming obesity and leptin resistance is still poorly understood.Objective:We aimed at determining whether nutritional intakes in early life are associated with body composition and hormonal status at 20 years.Subjects:Healthy infants participating in the two-decade-long prospective ELANCE (Etude Longitudinale Alimentation Nutrition Croissance des Enfants) study were examined at 10 months and 2 years. At 20 years, weight, height, subscapular and triceps skinfold thicknesses, fat mass (FM) and fat-free mass (FFM) assessed via bioelectrical impedance analysis, and serum leptin concentration were recorded in 73 subjects still participating in the follow-up.Results:In adjusted linear regression models, an increase by 100u2009kcal in energy intake at 2 years was associated with higher subscapular skinfold thickness (β=6.4% SF, 95% confidence interval 2.53–10.30, P=0.002) and higher FFM (0.50u2009kg, 0.06–0.95, P=0.03) at 20 years. An increase by 1% energy from fat at 2 years was associated with lower subscapular skinfold thickness (−2.3% SF, −4.41 to −0.18, P=0.03), lower FM (−0.31u2009kg, −0.60 to −0.01, P=0.04) and lower serum leptin concentration (−0.21u2009μgu2009l−1, −0.39 to −0.03, P=0.02) at 20 years.Conclusions:Low-fat intake in early life was negatively associated with body fat (particularly at the trunk site) and serum leptin concentration at 20 years, suggesting that early low-fat intake could increase the susceptibility to develop overweight and leptin resistance at later ages. These findings substantiate current recommendations against restricting fat intake in early life and open new directions for investigating the origin of obesity.

Interpretation of Plasma PTH Concentrations According to 25OHD Status, Gender, Age, Weight Status, and Calcium Intake: Importance of the Reference Values

CONTEXTnReference values for plasma PTH assessment were generally established on small samples of apparently healthy subjects, without considering their 25-hydroxyvitamin D (25OHD) status or other potential modifiers of PTH concentration.nnnOBJECTIVEnOur objective was to assess ranges of plasma PTH concentration in a large sample of adults, stratifying by 25OHD status, age, gender, weight status, and calcium intake.nnnDESIGN, SETTING, AND PARTICIPANTSnThis cross-sectional survey is based on 1824 middle-aged Caucasian adults from the Supplémentation en Vitamines et Minéraux Antioxydants study (1994).nnnMAIN OUTCOME MEASURESnPlasma PTH and 25OHD concentrations were measured by an electrochemoluminescent immunoassay. Extreme percentiles of plasma PTH concentrations were assessed specifically in subjects who had plasmatic values of 25OHD of 20 ng/mL or greater and 30 ng/mL or greater.nnnRESULTSnAmong subjects with 25OHD status of 20 ng/mL or greater, the 97.5th percentile of plasma PTH concentration was 45.5 ng/L. By using this value as a reference, 5% of the subjects with plasma 25OHD less than 20 nmol/L had a high plasma PTH level, reflecting secondary hyperparathyroidism. Among vitamin D-replete subjects (25OHD status of 20 ng/mL or greater), the 97.5th percentile of plasma PTH was higher in overweight/obese subjects (51.9 vs 43.5 ng/L among normal weight subjects).nnnCONCLUSIONSnThe reference value for plasma PTH defined in this vitamin D-replete population was far below the value currently provided by the manufacturer (65 ng/L) and varied according to overweight status. These results may contribute to improve the diagnosis of primary and secondary hyperparathyroidism and subsequent therapeutic indication.

A prospective study of plasma 25-hydroxyvitamin D concentration and prostate cancer risk.

Mechanistic hypotheses suggest that vitamin D and the closely related parathyroid hormone (PTH) may be involved in prostate carcinogenesis. However, epidemiological evidence is lacking for PTH and inconsistent for vitamin D. Our objectives were to prospectively investigate the association between vitamin D status, vitamin D-related gene polymorphisms, PTH and prostate cancer risk. A total of 129 cases diagnosed within the Supplémentation en Vitamines et Minéraux Antioxydants cohort were included in a nested case-control study and matched to 167 controls (13 years of follow-up). 25-Hydroxyvitamin D (25(OH)D) and PTH concentrations were assessed from baseline plasma samples. Conditional logistic regression models were computed. Higher 25(OH)D concentration was associated with decreased risk of prostate cancer (ORQ4 v. Q1 0·30; 95 % CI 0·12, 0·77; P trend=0·007). PTH concentration was not associated with prostate cancer risk (P trend=0·4) neither did the studied vitamin D-related gene polymorphisms. In this prospective study, prostate cancer risk was inversely associated with 25(OH)D concentration but not with PTH concentration. These results bring a new contribution to the understanding of the relationship between vitamin D and prostate cancer, which deserves further investigation.

Weight Status and Alcohol Intake Modify the Association between Vitamin D and Breast Cancer Risk

BACKGROUNDnMechanistic hypotheses suggest that vitamin D may contribute to the prevention of breast cancer. However, epidemiologic evidence is inconsistent, suggesting a potential effect modification by individual factors.nnnOBJECTIVEnOur objective was to perform exploratory analyses on the prospective associations between the plasma 25-hydroxyvitamin D [25(OH)D] concentration, polymorphisms of genes encoding for the vitamin D receptor (VDR) and vitamin D-binding protein (also known as gc-globulin or group-specific component, GC), and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m(2)) and alcohol intake.nnnMETHODSnA nested case-control study was set up in the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort (1994-2007), involving 233 women with breast cancer and 466 matched controls (mean ± SD age: 49 ± 6 y). The plasma total 25(OH)D concentration and gene polymorphisms were assessed on samples obtained at baseline. Conditional logistic regression models were computed.nnnRESULTSnA higher plasma 25(OH)D concentration was associated with a decreased risk of breast cancer for women with a BMI < the median of 22.4 [OR quartile (Q)4 compared with Q1: 0.46; 95% CI: 0.23, 0.89; P-trend = 0.01, P-interaction = 0.002], whereas it was associated with an increased risk for women with a BMI ≥ the median (OR Q4 compared with Q1: 2.45; 95% CI: 1.13, 5.28; P-trend = 0.02, P-interaction = 0.002). A plasma 25(OH)D concentration ≥ 10 ng/mL was associated with a decreased risk of breast cancer for women with alcohol intakes ≥ the median of 7.1 g/d (OR ≥10 compared with <10 ng/mL: 0.50; 95% CI: 0.26, 0.95; P = 0.03, P-interaction = 0.03). The genetic analyses were consistent with the results observed with plasma 25(OH)D.nnnCONCLUSIONnIn this prospective study, BMI and alcohol intake modified the association between vitamin D [plasma 25(OH)D and vitamin D-related gene polymorphisms] and breast cancer risk. These effect modifications suggest explanations for discrepancies in results of previous studies. This trial was registered at clinicaltrials.gov as NCT00272428.

Prospective associations between vitamin D status, vitamin D–related gene polymorphisms, and risk of tobacco-related cancers

BACKGROUNDnExperimental evidence has suggested that vitamin D may be protective against tobacco-related cancers through the inhibition of the formation of tumors induced by tobacco carcinogens. To our knowledge, only one previous epidemiologic study investigated the association between vitamin D status and tobacco-related cancer risk, and no study has focused on vitamin D-related gene polymorphisms.nnnOBJECTIVEnOur objective was to prospectively study the association between plasma 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D-related gene polymorphisms, and risk of tobacco-related cancers.nnnDESIGNnA total of 209 tobacco-related cancers were diagnosed within the SU.VI.MAX (Supplémentation en vitamines et minéraux antioxydants) cohort (1994-2007) and were matched with 418 controls as part of a nested case-control study. Tobacco-related cancers (i.e., cancers for which tobacco is one of the risk factors) included several sites in the respiratory, digestive, reproductive, and urinary systems. Total plasma 25(OH)D was assessed with the use of an electrochemoluminescent assay. Polymorphisms were determined with the use of a TaqMan assay. Conditional logistic regression models were computed.nnnRESULTSnA 25(OH)D concentration ≥30 ng/mL was associated with reduced risk of tobacco-related cancers (OR for ≥30 compared with <30 ng/mL: 0.59; 95% CI 0.35, 0.99; P = 0.046). This association was observed in former and current smokers (OR for ≥30 compared with <30 ng/mL: 0.43; 95% CI: 0.23, 0.84; P = 0.01) but not in never smokers (P = 0.8). The vitamin D receptor (VDR) FokI AA genotype and retinoid X receptor (RXR) rs7861779 TT genotype were associated with increased risk of tobacco-related cancers [OR for homozygous mutant type (MT) compared with wild type (WT): 1.87; 95% CI: 1.08, 3.23; P-trend = 0.02; OR for heterozygous type (HT) plus MT compared with WT: 1.60; 95% CI: 1.07, 2.38; P = 0.02].nnnCONCLUSIONSnIn this prospective study, high vitamin D status [25(OH)D concentration ≥30 ng/mL] was associated with decreased risk of tobacco-related cancers, especially in smokers. These results, which are supported by mechanistic plausibility, suggest that vitamin D may contribute to the prevention of tobacco-induced cancers in smokers and deserve additional investigation. The SU.VI.MAX trial was registered at clinicaltrials.gov as NCT00272428.

Le dosage de la 25-hydroxy-vitamine D dans l’ostéoporose : de la physiologie à la pratique

Resume La source principale de vitamine D correspond a la synthese cutanee apres exposition a des rayonnements UVB. La vitamine D doit etre transformee en 25OH vitamine D (25OHD) puis en calcitriol avant de devenir pleinement active. Ce n’est donc pas une vitamine stricto sensu mais plutot une preprohormone. A cote de ses effets classiques sur le metabolisme phosphocalcique et osseux, la vitamine D a des effets potentiels sur de tres nombreuses autres fonctions. Le statut vitaminique D est consensuellement defini par la concentration serique de 25OHD. Pour une majorite d’experts, une valeur