G R Goldberg

Vitamin D deficiency in Europe: pandemic?

Background: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys. Objective: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe. Design: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography–tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n = 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data. Results: An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October–March) and summer (April–November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations. Conclusions: Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population.

Global Consensus Recommendations on Prevention and Management of Nutritional Rickets

Background: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. Evidence: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. Process: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. Results: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. Conclusion: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

Effects of weight cycling on body composition.

It is frequently claimed that weight cycling, or yo-yo dieting, causes an inappropriate and permanent loss of lean body mass (LBM). Data are presented from a rural African population that undergoes profound weight cycling caused by an annual hungry season. No detrimental effect on LBM was observed. Data are also presented from an 18-wk prospective study of moderately obese British women who underwent three cycles of VLCD-induced weight loss and subsequent relapse. The proportion of weight lost as LBM was no greater than predicted. A review of the published results from experimental weight cycling in small animals also shows a high level of consensus that cycling does not significantly alter body composition. We conclude that, although weight cycling may affect growth of young animals, metabolic efficiency, and health, these effects are not mediated through permanent alterations in body composition.

Effects of inactivity and diet composition on human energy balance.

OBJECTIVES: To investigate the influences of inactivity and dietary macronutrient composition on energy and fat balance and to look for interactions between them.DESIGN: Two-day measurements of energy expenditure and substrate oxidation on five occasions; ad libitum food intake from diets of 35% and 60% energy as fat, with and without imposed activity, and a fixed overfeeding at 35% fat with free activity.SUBJECTS: Eight normal-weight male volunteers.MEASUREMENTS: Energy expenditure and substrate oxidation by indirect whole-body calorimetry, and macro-nutrient intakes from food consumption on ad libitum regimens.RESULTS: Subjects consumed the same energy, mean 11.6u2005MJ/d, regardless of activity level, on the 35% diet. Subjects consumed more energy on the 60% than the 35% diet, mean 14 vs 11.6u2005MJ/d. Inactivity induced a strong positive energy balance: 5.1 (60% diet), and 2.6u2005MJ/d (35% diet). Energy balance with activity was not significantly different between diets, nor significantly different from zero: 1.1u2005MJ/d (60% diet), and −0.2u2005MJ/d (35% diet). When intentionally overfed, subjects failed to compensate by raising voluntary activity.CONCLUSION: Energy intake was not regulated over a 2-day period in response to either imposition of inactivity or a high-fat diet. Activity proved essential to the avoidance of significant positive energy balance.

Energy-sparing strategies to protect human fetal growth

OBJECTIVESnOur purpose was to test whether energy-sensitive adjustments in gestational metabolism, previously observed in studies of Gambian and British women, are a general phenomenon and to define the nutritional factors that direct them.nnnSTUDY DESIGNnRetrospective analysis of data on basal metabolic rate and fat deposition in 360 pregnancies from 10 studies in a wide range of nutritional settings was performed.nnnRESULTSnThe energy costs of pregnancy varied widely between different communities: maintenance costs from -45 to +210 MJ, fat deposition from -23 to +267 MJ, and total energy costs from -20 to +523 MJ. Total costs were correlated with prepregnancy fatness (r = 0.80, p < 0.01) and pregnancy weight gain (r = 0.94, p < 0.001). Marginally nourished women conserved energy by suppressing metabolic rate and by gaining little fat.nnnCONCLUSIONSnThe energy needs of pregnancy are modulated over a wide range in response to maternal energy status. This may be an important means of protecting fetal growth.

Iron status and fibroblast growth factor-23 in Gambian children

A relationship between iron and fibroblast growth factor-23 (FGF23) metabolic pathways has been proposed. Iron deficiency anaemia is prevalent in The Gambia and concentrations of fibroblast growth factor-23 FGF23 are elevated in a large percentage of Gambian children with rickets-like bone deformity. We speculate that low iron status may be involved in the aetiology of Gambian rickets. The aim of this study was to determine if there was a relationship between haemoglobin, as a marker of iron status, and FGF23 in samples from children with and without a history of rickets-like bone deformities in The Gambia. We conducted a retrospective analysis of studies carried out from 2006 to 2008 in children from a rural community in The Gambia where iron deficiency anaemia is endemic and where elevated circulating concentrations of FGF23 have been found. To investigate the relationship between circulating FGF23 and haemoglobin concentrations we used an age-adjusted linear regression model on data from children < 18 y of age with a family or personal history of rickets-like bone deformity (BD) (n = 108) and from the local community (LC) (n = 382). We found that circulating concentration of FGF23 was inversely correlated with haemoglobin concentration. This effect was more pronounced in BD children compared with LC children (interaction: P ≤ 0.0001). Anaemia and elevated FGF23 were more prevalent in BD children compared to LC children (P = 0.0003 and P = 0.0001 respectively). In conclusion, there is a stronger relationship between FGF23 and haemoglobin in Gambian children with a history of rickets compared to local community children. This study provides support for the contention that iron may be involved in FGF23 metabolic pathways.

Non-invasive techniques for assessing carbohydrate flux

Glycogen forms the smallest yet most labile energy substrate store. Therefore studying carbohydrate flux may be crucial to understanding the regulation of energy balance. Indirect calorimetry has been used to measure carbohydrate oxidation overnight and during exercise in nine fasted subjects. Overnight carbohydrate oxidation (averaging 2.85 +/- 0.8 g h-1) was assumed to be derived primarily from hepatic glycogen since subjects were inactive or asleep, and since glucose oxidized after gluconeogenesis from protein is measured as protein oxidation. Lower-limb muscle glycogen stores were depleted by repeated 30-min periods of cycle ergometry at 45% VO2max until exhaustion (8 +/- 1 periods). The carbohydrate oxidation rate decreased as exercise progressed. Quadratic curves yielded a close fit to each individuals exercise carbohydrate depletion data (mean multiple correlation r = 0.9996) and provided excellent inter-subject discrimination. Total (muscle plus liver) glycogen stores prior to exercise were estimated by extrapolation of the depletion curves to zero oxidation rate. This produced an extrapolation of the depletion curves to zero oxidation rate. This produced an estimate (174 +/- 61 g) which compared well with predictions (208 +/- 43 g) based on reference values for muscle mass and initial glycogen content. The results demonstrate that non-invasive estimates of glycogen status can be obtained from accurate respiratory exchange data.

Dietary intake and body composition in HIV-positive and -negative South African women

OBJECTIVEnThe present paper examines dietary intake and body composition in antiretroviral (ARV)-naïve HIV-positive compared with HIV-negative South African women, as well as the impact of disease severity on these variables.nnnDESIGNnBaseline data from a longitudinal study assessing bone health in HIV-negative and HIV-positive premenopausal South African women over 18 years of age were used. Anthropometry and body composition, measured by dual energy X-ray absorptiometry, were analysed together with dietary intake data assessed using an interviewer-based quantitative FFQ.nnnSETTINGnSoweto, Johannesburg, South Africa.nnnSUBJECTSnBlack, urban South African women were divided into three groups: (i) HIV-negative (HIV-; n 98); (ii) HIV-positive with preserved CD4 counts (HIV+ non-ARV; n 74); and (iii) HIV-positive with low CD4 counts and due to start ARV treatment (HIV+ pre-ARV; n 75).nnnRESULTSnThe prevalence of overweight and obesity was high in this population (59 %). The HIV+ pre-ARV group was lighter and had a lower BMI than the other two groups (all P < 0·001). HIV+ pre-ARV women also had lower fat and lean masses and percentage body fat than their HIV- and HIV+ non-ARV counterparts. After adjustment, there were no differences in macronutrient intakes across study groups; however, fat and sugar intakes were high and consumption of predominantly refined food items was common overall.nnnCONCLUSIONnHIV-associated immunosuppression may be a key determinant of body composition in HIV-positive women. However, in populations with high obesity prevalence, these differences become evident only at advanced stages of infection.

Leptin does not respond to 48 h fat deposition or mobilization in women.

OBJECTIVE: To test the hypothesis that acute responses of plasma leptin concentration to energy balance manipulation are mediated by fat flux.DESIGN: Ten healthy women aged 31–63u2009y, mass 48–113.5u2009kg, fat mass 8.5–62.5u2009kg, were studied for 3 days in a whole-body calorimeter on two occasions. After a control day (D1) during which energy balance was maintained, diet was manipulated to induce fat deposition (FD) or mobilization (FM) of 50u2009g/day for 2 days (D2 & D3). A difference totalling of 194±18.6u2009g fat was achieved between manipulations without significant effects on carbohydrate or protein balance. Fasting plasma leptin was measured on D2 and D4.RESULTS: After the control day plasma leptin concentration averaged 19.01±9.8u2009ng/ml, and was found to be linearly related to body fat mass. After 2 days manipulation of fat balance, leptin concentrations were 21.4±10.3u2009ng/ml (FD) and 21.2±11.3u2009ng/ml (FM). There was no significant difference between treatments in either control day or postmanipulation leptin concentrations, nor did the treatments induce any differences in glucose or insulin concentration responses.CONCLUSION: Although in states of energy balance leptin concentration is linearly related to fat mass, acute modulation of leptin concentration during energy imbalance is not mediated by fat flux.

Candidate genes linking maternal nutrient exposure to offspring health via DNA methylation: a review of existing evidence in humans with specific focus on one-carbon metabolism.

Abstract Background Mounting evidence suggests that nutritional exposures during pregnancy influence the fetal epigenome, and that these epigenetic changes can persist postnatally, with implications for disease risk across the life course. Methods We review human intergenerational studies using a three-part search strategy. Search 1 investigates associations between preconceptional or pregnancy nutritional exposures, focusing on one-carbon metabolism, and offspring DNA methylation. Search 2 considers associations between offspring DNA methylation at genes found in the first search and growth-related, cardiometabolic and cognitive outcomes. Search 3 isolates those studies explicitly linking maternal nutritional exposure to offspring phenotype via DNA methylation. Finally, we compile all candidate genes and regions of interest identified in the searches and describe their genomic locations, annotations and coverage on the Illumina Infinium Methylation beadchip arrays. Results We summarize findings from the 34 studies found in the first search, the 31 studies found in the second search and the eight studies found in the third search. We provide details of all regions of interest within 45 genes captured by this review. Conclusions Many studies have investigated imprinted genes as priority loci, but with the adoption of microarray-based platforms other candidate genes and gene classes are now emerging. Despite a wealth of information, the current literature is characterized by heterogeneous exposures and outcomes, and mostly comprise observational associations that are frequently underpowered. The synthesis of current knowledge provided by this review identifies research needs on the pathway to developing possible early life interventions to optimize lifelong health.