Time filter

Source Type

Jarjou L.M.A.,Medical Research Council Keneba | Sawo Y.,Medical Research Council Keneba | Goldberg G.R.,Medical Research Council Keneba | Goldberg G.R.,Medical Research Council | And 4 more authors.
American Journal of Clinical Nutrition | Year: 2013

Background: Calcium supplementation of pregnant Gambian women with a low calcium intake results in lower maternal bone mineral content in the subsequent lactation. Objective: The objective was to investigate whether the lower bone mineral content persists long term. Design: All women in the calcium supplementation trial (International Trial Registry ISRCTN96502494) who had been scanned with dual-energy X-ray absorptiometry at 52 wk of lactation (L52; n = 79) were invited for follow-up when neither pregnant nor lactating for ≥3 mo (NPNL) or at 52 wk postpartum in a future lactation (F52). Bone scans and anthropometric and dietary assessments were conducted. Results: Sixty-eight women participated (35 at both NPNL and F52 and 33 at only one time point): n = 59 NPNL (n = 31 calcium, n = 28 placebo) and n = 44 F52 (n = 24 calcium, n = 20 placebo). The mean (±SD) time from L52 was 4.9 ± 1.9 y for NPNL and 5.0 ± 1.3 y for F52. Size-adjusted bone mineral content (SA-BMC) was greater at NPNL than at L52 in the placebo group (P ≤ 0.001) but not in the calcium group (P for time-by-group interaction: lumbar spine, 0.002; total hip, 0.03; whole body, 0.03). No significant changes in SA-BMC from L52 to F52 were observed in either group. Consequently, the lower SA-BMC in the calcium group at L52 persisted at NPNL and F52 (P ≤ 0.001): NPNL (lumbar spine, -7.5 ± 0.7%; total hip, -10.5 ± 1.0%; whole body, -3.6 ± 0.5%) and F52 (lumbar spine, -6.2 ± 0.9%; total hip, -10.3 ± 1.4%; whole body, -3.2 ± 0.6%). Conclusion: In rural Gambian women with a low-calcium diet, a calcium supplement of 1500 mg/d during pregnancy resulted in lower maternal bone mineral content in the subsequent lactation that persisted long term. This trial was registered at www/controlledtrials.com/mrct/as ISRCTN96502494. © 2013 American Society for Nutrition.


Atkinson S.H.,University of Oxford | Atkinson S.H.,Kenya Medical Research Institute | Armitage A.E.,Weatherall Institute of Molecular Medicine | Khandwala S.,Kenya Medical Research Institute | And 9 more authors.
Blood | Year: 2014

Hepcidin is themaster regulatory hormone that governs iron homeostasis and has a role in innate immunity.Although hepcidin has been studied extensively inmodel systems, there is less information on hepcidin regulation in global health contexts where iron deficiency (ID), anemia, and high infectious burdens (including malaria) all coexist but fluctuate over time. We evaluated iron status, hepcidin levels, and determinants of hepcidin in 2 populations of rural children aged £8 years, in the Gambia and Kenya (total n5 848), at the start and end of amalaria season. Regression analyses and structural equationmodeling demonstrated, for both populations, similar combinatorial effects of upregulating stimuli (iron stores and to a lesser extent inflammation) and downregulating stimuli (erythropoietic drive) on hepcidin levels. However, malaria season was also a significant factor and was associated with an altered balance of these opposing factors. Consistent with these changes, hepcidin levels were reduced whereas the prevalence of ID was increased at the end of the malaria season. More prevalent ID and lower hepcidin likely reflect an enhanced requirement for iron and an ability to efficiently absorb it at the end of themalaria season. These results, therefore, have implications for ID and malaria control programs. © 2014 by The American Society of Hematology.


Hawkesworth S.,London School of Hygiene and Tropical Medicine | Sawo Y.,Medical Research Council Keneba | Fulford A.J.C.,London School of Hygiene and Tropical Medicine | Fulford A.J.C.,Medical Research Council Keneba | And 6 more authors.
American Journal of Clinical Nutrition | Year: 2010

Background: Evidence suggests that increased maternal calcium intake during pregnancy may result in lower offspring blood pressure, prompting calls for more robust data in this field, particularly in settings of habitually low calcium intake. Objective: The objective was to investigate the effect of maternal calcium supplementation on blood pressure in offspring by recruiting children born after a randomized, double-blind, placebo-controlled trial of calcium supplementation during pregnancy. Design: Children (n = 389) from a rural area of The Gambia (mean age: 7.4 ± 1.2 y; range: 5-10 y), whose mothers received a calcium supplement (1500 mg Ca/d from 20 wk of gestation until delivery) or placebo, were followed up in West Africa. Blood pressure was assessed under standardized conditions with use of the Omron 705IT automated oscillometric device (Morton Medical Ltd, London, United Kingdom), and anthropometric and body composition (bioelectrical impedance) measurements were also made. Results: The analysis was restricted to 350 children born at term, which represented 64% of original trial births. There was no difference in systolic (adjusted mean difference: -0.04 mm Hg; 95% CI: -1.78, 1.69 mm Hg) or diastolic (adjusted mean difference: 0.25 mm Hg; 95% CI: -1.27, 1.77 mm Hg) blood pressure between children whose mothers had received calcium and those who received placebo. No interaction between childhood body mass index (in kg/m 2; mean: 14.0) and maternal calcium supplementation was observed in this study. Conclusion: Calcium supplementation in the second half of pregnancy in Gambian women with very low habitual calcium intakes may not result in lower offspring blood pressure at 5-10 y of age. © 2010 American Society for Nutrition.


Redmond J.,Medical Research Council Human Nutrition Research | Palla L.,Medical Research Council Human Nutrition Research | Palla L.,London School of Hygiene and Tropical Medicine | Yan L.,Medical Research Council Human Nutrition Research | And 4 more authors.
Osteoporosis International | Year: 2015

Summary: Ethnic differences in renal calcium and phosphate excretion exist, which may depend on differences in their dietary intakes and regulatory factors. We report highly significant differences in urinary calcium and phosphate excretion between white British and Gambian adults after statistical adjustment for mineral intakes, indicating an independent effect of ethnicity.Methods: Participants were healthy white British (n = 60) and Gambian (n = 61) men and women aged 60–75 years. Fasting blood and 2-h urine samples were collected. Markers of Ca and P metabolism were analysed. Dietary intake was assessed with country-specific methods.Introduction: Populations vary in their risk of age-related osteoporosis. There are racial or ethnic differences in the metabolism of the bone-forming minerals calcium (Ca) and phosphate (P), with a lower renal Ca and P excretion in African-Americans compared to white counterparts, even at similar intakes and rates of absorption. Also, Africans in The Gambia have a lower Ca excretion compared to white British subjects, groups known to differ in their dietary Ca intake. Here, we report on differences in urinary Ca and P excretion between Gambian and white British adults while allowing for known predictors, including dietary intakes.Results: White British older adults had higher creatinine-corrected urinary Ca and P excretion (uCa/uCr, uP/uCr) and lower tubular maximum of Ca and P compared to Gambian counterparts. The predictors of urinary Ca and P differed between groups. Multiple regression analysis showed that dietary Ca and Ca/P were predictors of uCa/uCr and uP/uCr, respectively. Ethnicity remained a significant predictor of uCa/uCr and uP/uCr after adjustment for diet and other factors.Conclusions: Gambian older adults have higher renal Ca conservation than British counterparts. Dietary mineral intakes were predictors of the differences in urinary Ca and P excretion, but ethnicity remained a highly significant predictor after statistical adjustment. This suggests that ethnicity has an independent effect on renal Ca and P handling. © 2014, The Author(s).


Clark M.A.,University of North Carolina at Chapel Hill | Goheen M.M.,University of North Carolina at Chapel Hill | Spidale N.A.,University of North Carolina at Chapel Hill | Kasthuri R.S.,University of North Carolina at Chapel Hill | And 3 more authors.
PLoS ONE | Year: 2014

Plasmodium falciparum invasion of host erythrocytes is essential for the propagation of the blood stage of malaria infection. Additionally, the brief extracellular merozoite stage of P. falciparum represents one of the rare windows during which the parasite is directly exposed to the host immune response. Therefore, efficient invasion of the host erythrocyte is necessary not only for productive host erythrocyte infection, but also for evasion of the immune response. Host traits, such as hemoglobinopathies and differential expression of erythrocyte invasion ligands, can protect individuals from malaria by impeding parasite erythrocyte invasion. Here we combine RBC barcoding with flow cytometry to study P. falciparum invasion. This novel high-throughput method allows for the (i) direct comparison of P. falciparum invasion into different erythrocyte populations and (ii) assessment of the impact of changing erythrocyte population dynamics on P. falciparum invasion. © 2014 Clark et al.


Redmond J.,Medical Research Council Human Nutrition Research | Jarjou L.M.A.,Medical Research Council Keneba | Zhou B.,Shenyang Medical College | Prentice A.,Medical Research Council Human Nutrition Research | And 2 more authors.
Proceedings of the Nutrition Society | Year: 2014

The prevalence of osteoporosis and the incidence of age-related fragility fracture vary by ethnicity. There is greater than 10-fold variation in fracture probabilities between countries across the world. Mineral and bone metabolism are intimately interlinked, and both are known to exhibit patterns of daily variation, known as the diurnal rhythm (DR). Ethnic differences are described for Ca and P metabolism. The importance of these differences is described in detail between select ethnic groups, within the USA between African-Americans and White-Americans, between the Gambia and the UK and between China and the UK. Dietary Ca intake is higher in White-Americans compared with African-Americans, and is higher in White-British compared with Gambian and Chinese adults. Differences are observed also for plasma 25-hydroxy vitamin D, related to lifestyle differences, skin pigmentation and skin exposure to UVB-containing sunshine. Higher plasma 1,25-dihydroxy vitamin D and parathyroid hormone are observed in African-American compared with White-American adults. Plasma parathyroid hormone is also higher in Gambian adults and, in winter, in Chinese compared with White-British adults. There may be ethnic differences in the bone resorptive effects of parathyroid hormone, with a relative skeletal resistance to parathyroid hormone observed in some, but not all ethnic groups. Renal mineral excretion is also influenced by ethnicity; urinary Ca (uCa) and urinary P (uP) excretions are lower in African-Americans compared with White-Americans, and in Gambians compared with their White-British counterparts. Little is known about ethnic differences in the DR of Ca and P metabolism, but differences may be expected due to known differences in lifestyle factors, such as dietary intake and sleep/wake pattern. The ethnic-specific DR of Ca and P metabolism may influence the net balance of Ca and P conservation and bone remodelling. These ethnic differences in Ca, P and the bone metabolism may be important factors in the variation in skeletal health. © The Authors 2014.


Prentice A.,MRC Human Nutrition Research | Prentice A.,Medical Research Council Keneba | Dibba B.,Medical Research Council Keneba | Sawo Y.,Medical Research Council Keneba | Cole T.J.,University College London
American Journal of Clinical Nutrition | Year: 2012

Background: Limited evidence suggests that calcium intake before puberty influences adolescent height growth and the timing of puberty. Such an effect might be particularly marked in populations in whom low calcium intake, stunting, and delayed puberty are common. Objective: The objective was to test whether 12 mo of calcium supplementation at age 8-12 y to increase intakes toward international recommendations had long-term effects on adolescent growth and pubertal development in rural Gambian children. Design: This was a longitudinal study of 160 Gambian boys (n = 80) and girls (n = 80) who had participated in a 12-mo, randomized, double-blind, placebo-controlled, calcium carbonate supplementation trial (1000 mg Ca/d, 5 d/wk) at age 8-12 y. Anthropometric measures were made every 1-2 y until age 21-25 y; pubertal status and menarche data were collected. Repeated-measures ANCOVA and Superimposition by Translation and Rotation Method (SITAR) growth models were used to assess the effects of treatment. Results: In boys, midadolescent height growth was advanced in the calcium group, which resulted in greater stature at a mean age of 15.5 y (mean ± SEM: 2.0 ± 0.8 cm; P = 0.01) and an earlier age of peak height velocity by 7.4 ± 2.9 mo. Subsequently, the calcium group stopped growing earlier (P = 0.02) and was 3.5 ± 1.1 cm shorter (P = 0.002) at a mean age of 23.5 y. Weight and midupper arm circumference paralleled height. No significant effects were observed in girls, but a sex-by-supplement interaction on height growth could not be confirmed. Conclusion: Calcium supplementation of boys in late childhood advanced the age of peak height velocity and resulted in shorter adult stature in a population in whom low calcium intakes and delayed puberty are common. This trial was registered at isrctn.org as ISRCTN28836000. © 2012 American Society for Nutrition.


Jones K.S.,Medical Research Council Human Nutrition Research | Jones K.S.,Medical Research Council Keneba | Assar S.,Medical Research Council Human Nutrition Research | Vanderschueren D.,Catholic University of Leuven | And 6 more authors.
Osteoporosis International | Year: 2015

Conclusion: Factors known to affect 25(OH)D metabolism predict 25(OH)D3 half-life, but these differed between countries. Country predicted 25(OH)D, probably as a proxy measure for UVB exposure and vitamin D supply. This study supports the use of 25(OH)D half-life to investigate vitamin D metabolism.Summary: Predictors of 25(OH)D3 half-life were factors associated with vitamin D metabolism, but were different between people in The Gambia and the UK. Country was the strongest predictor of plasma 25(OH)D concentration, probably as a marker of UVB exposure. 25(OH)D3 half-life may be applied as a tool to investigate vitamin D expenditure.Introduction: The aim of this study was to investigate predictors of 25(OH)D3 half-life and plasma 25(OH)D concentration.Methods: Plasma half-life of an oral tracer dose of deuterated-25(OH)D3 was measured in healthy men aged 24–39 years, resident in The Gambia, West Africa (n = 18) and in the UK during the winter (n = 18), countries that differ in calcium intake and vitamin D status. Plasma and urinary markers of vitamin D, calcium, phosphate and bone metabolism, nutrient intakes and anthropometry were measured.Results: Normally distributed data are presented as mean (SD) and non-normal data as geometric mean (95 % CI). Gambian compared to UK men had higher plasma concentrations of 25(OH)D (69 (13) vs. 29 (11) nmol/L; P < 0.0001); 1,25(OH)2D (181 (165, 197) vs. 120 (109, 132) pmol/L; P < 0.01); and parathyroid hormone (PTH) (50 (42, 60) vs. 33 (27, 39); P < 0.0001). There was no difference in 25(OH)D3 half-life (14.7 (3.5) days vs. 15.6 (2.5) days) between countries (P = 0.2). In multivariate analyses, 25(OH)D, 1,25(OH)2D, vitamin D binding protein and albumin-adjusted calcium (Caalb) explained 79 % of variance in 25(OH)D3 half-life in Gambians, but no significant predictors were found in UK participants. For the countries combined, Caalb, PTH and plasma phosphate explained 39 % of half-life variability. 1,25(OH)2D, weight, PTH and country explained 81 % of variability in 25(OH)D concentration; however, country alone explained 74 %. © 2014, The Author(s).


Jones K.S.,Medical Research Council Human Nutrition Research | Jones K.S.,Medical Research Council Keneba | Assar S.,Medical Research Council Human Nutrition Research | Harnpanich D.,Medical Research Council Human Nutrition Research | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Objective: The objective of the study was to compare the plasma half-lives of 25(OH)D2and 25(OH)D3in two distinct populations with different dietary calcium intake and 25(OH)D status.Participants: Healthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study.Interventions: The intervention included an oral tracer dose of deuterated-25(OH)D2and deuterated-25(OH)D3(both 40 nmol). Blood samples were collected over 33 days.Main Outcome Measures: 25(OH)D2and 25(OH)D3plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured.Results: 25(OH)D2half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3half-life [15.1 (3.1) d; P=.001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P<.001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2half-life: regression coefficient (SE) 0.03 (0.01)dper 1 mg/L DBP, P=.03;25(OH)D3half-life: 0.04 (0.02) d, P=.02]andinGambians[25(OH)D2half-life: 0.04 (0.01) d; P = .02; 25(OH)D3half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration×country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2half-lives compared with other combined genotypes (P = .007) after correction for country.Conclusions: 25(OH)D2half-life was shorter than 25(OH)D3half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.Context: There is uncertainty over the equivalence of vitamins D2and D3to maintain plasma 25-hydroxyvitamin D (25(OH)D). Copyright © 2014 by the Endocrine Society.

Loading Medical Research Council Keneba collaborators
Loading Medical Research Council Keneba collaborators