Dorothy M. Stirling

A trial of zinc supplementation in young rural Gambian children

The present study tested the hypothesis that inadequate Zn intake might be responsible for failure to thrive and impaired catch-up growth in young rural Gambian children, and that Zn supplements might be beneficial. Gambian children might be deprived of Zn because of its poor availability from their predominantly plant-based diet. Rural Gambian children (110; fifty boys, sixty girls) aged between 0.57 and 2.30 years were divided into two matched groups, one to receive 70 mg Zn twice weekly for 1.25 years, and the other a placebo. Growth and mid-upper-arm circumference were measured at weekly intervals throughout the study and illnesses were monitored. Capillary blood and urine samples were collected at 0, 2 and 8 weeks. Body weights and arm circumferences showed a linear increase, plus a seasonal effect (rainy season faltering). For body weight there was no significant overall effect of the supplement. For arm circumference, a very small (2%) but significant (P < 0.01) difference favoured the supplemented group. Plasma thymulin was much lower at the first clinic than at the second and third clinics, and in vitro Zn stimulation was greater at the first clinic. There was, however, no effect of Zn in vivo. Likewise, Zn did not significantly benefit T-cell numbers or ratios, secretory IgA in urine, circulating hormone levels or biochemical indices of Zn status. One index of intestinal permeability, i.e. lactulose: creatinine, was improved (P < 0.02) by the supplement, but the lactulose: mannitol value was not; this requires further investigation. Dietary Zn deficiency is, thus, unlikely to be of major overall importance for rural Gambian childrens ability to thrive, and blanket Zn supplementation is not justified. There may, however, be vulnerable sub-groups who would benefit from Zn supplements.

Bone mineralization and turnover in preterm infants at 8-12 years of age: The effect of early diet

Our previous studies raised two hypotheses: first that suboptimal early nutrition and second that human milk have enhancing effects on long‐term bone mineralization. To test these hypotheses experimentally, we measured whole body and regional bone mineral content (BMC) and bone mineral density (BMD), using dual‐energy X‐ray absorptiometry and single‐photon absorptiometry, and bone turnover at 8–12 years in 244 preterm children (128 boys) who participated in a prospective randomized study of diet during the neonatal period. Dietary randomizations studied were: banked human milk (BBM, n = 87) versus preterm formula (PTF, n = 96) as the sole diet or as a supplement to mothers expressed breast milk (EBM); PTF (n = 25) versus term formula (TF, n = 36) as sole diet. Ninety‐five term children of the same age were also studied. First, preterm children were shorter and lighter than term children (height SD scores −0.49 (1.1) vs. +0.22 (0.9), weight SD scores −0.41 (1.2) vs. +0.38 (1.0) and had significantly lower whole‐body BMC than their peers; decrements were also evident at some regional sites. These differences disappeared after adjusting for bone area, body size, and pubertal status. Second, children previously randomized to BBM versus PTF or TF versus PTF showed no significant differences in anthropometry, BMC, BMD, or osteocalcin (OC). Third, there was no independent effect of the proportion of EBM on BMC, BMD, or OC and no interaction between randomized diet and the amount of EBM received. Fourth, plasma OC was significantly higher in preterm children than in term children (12.4 vs. 11.0 ng/ml, p < 0.005) and in preterm children who had received a low‐nutrient (BBM/TF) as opposed to a high‐nutrient diet (PTF) during the neonatal period (12.9 vs. 11.9 ng/ml, p = 0.03). In conclusion, preterm children are shorter, lighter, and have lower bone mass than their peers at age 8–12 years. The lower BMC is, however, appropriate for the bone and body size achieved. Despite large differences in early mineral intake, early diet does not affect bone mass in preterm children, and fresh human milk has no specific effect. However, poor nutrition during the neonatal period may result in higher bone formation rates during childhood.

Effect of acclimation temperature on the concentration of the mitochondrial ‘uncoupling’ protein measured by radioimmunoassay in mouse brown adipose tissue

The effect of acclimation temperature on the concentration of the mitochondrial ‘uncoupling’ protein (M r 32 000) from brown adipose tissue of mice has been investigated. The uncoupling protein was measured by a specific radioimmunoassay. Between 33°C (thermoneutrality) and −2°C there was a progressive increase with decreasing environmental temperature in the amount of uncoupling protein. For mice at −2°C the mitochondrial concentration of the protein was 9‐times higher than at 33°C, while the total amount of the protein in interscapulaar brown adipose tissue was estimated to be nearly 80‐times greater at −2°C compared to 33°C.

Vitamin D Status Does Not Influence the Breast-Milk Calcium Concentration of Lactating Mothers Accustomed to a Low Calcium Intake

Plasma 25‐hydroxy‐vitamin D and breast‐milk calcium concentration were measured at 3 months of lactation in 60 Gambian mothers accustomed to a low calcium diet, of whom 30 were consuming a calcium supplement and 30 were receiving a placebo, and in 48 British mothers. The plasma 25‐hydroxy‐vitamin D concentration of the Gambian women was not affected by either calcium supplementation (supplemented, 64. 4 ± 2. 5 nmol 1‐1; placebo, 64. 9 ± 3. 5 nmol l‐1; mean ± SE) or season. The British average was lower (53. 9 ± 3. 0 nmol 1‐1, p= 0. 004), owing to marked seasonal effects. The breast‐milk calcium concentration was lower in The Gambia (supplemented, 5. 38 ± 0. 13 mmol 1‐1; placebo, 5. 10 ± 0. 13mmol 1‐1; British, 6. 93 ± 0. 15 mmol 1‐1, p < 0. 0001). There was no relationship between plasma 25‐hydroxy‐vitamin D and breast‐milk calcium concentration in any group. There was no trend towards lower breast‐milk calcium concentration in women with vitamin D status towards the bottom of the normal range or in British women during the winter. This study provides no support for the hypothesis that breast‐milk calcium concentration is influenced by vitamin D status or that lactating women with a low calcium intake are at particular risk of vitamin D deficiency.

An investigation of ethnic differences in bone mineral, hip axis length, calcium metabolism and bone turnover between West African and Caucasian adults living in the United Kingdom.

The aim of the study was to investigate factors relating to calcium and bone metabolism which might explain the low incidence of osteoporotic fracture among Africans. Adult bone mineral status, hip axis length and biochemical indices were investigated in 20 Caucasians (10 male, 10 female) and 19 Gambians (12 male, 7 female) living in the UK. Bone mineral content (BMC), bone mineral density (BMD) and BMC adjusted for bone area, body weight and height (size-adjusted BMC) were measured for the whole-body, lumbar spine, femoral neck, trochanter, radius shaft and radius wrist using dual-energy X-ray absorptiometry. There were no significant differences in whole body or regional BMC; values tended to be lower in the Gambians. Gambian men had higher size-adjusted BMC at the femoral neck (Gambian-British = 21%, 95% CI = 6 to 36%, p < 0.01), associated with a smaller bone area (Gambian-British = -11%, 95% CI = -20 to -2%, p = 0.02). BMD was affected similarly. No other significant differences in BMD or size-adjusted BMC were observed. Gambians had shorter hip axis length (Gambian British, after accounting for sex, = -5%, 95% CI = -9 to -1%, p = 0.02). There were no significant differences in bone turnover (osteocalcin, bone isoenzyme of alkaline phosphatase, urinary deoxypyridinoline) or calciotropic hormone levels (parathyroid hormone, 1,25-dihydroxyvitamin D, calcitonin). Gambian men had lower 25-hydroxyvitamin D concentrations (Gambian = 26.3 SD 12.0 nmol/L, British = 55.5 SD 13.9 nmol/L, p < 0.0001), a difference not seen among the women. Gambian men and women excreted significantly less phosphate and potassium than British subjects by 30-60%; urinary calcium and sodium excretion were similar in the two groups. This study revealed few ethnic differences that could account for the disparity in osteoporotic fracture rates between Africans and Caucasians, with the possible exception of anatomical differences in the hip.

The effect of long-term calcium supplementation on indices of iron, zinc and magnesium status in lactating Gambian women

The effect of long-term supplementation with CaCO3 on indices of Fe, Zn and Mg status was investigated in a randomized, double-blind intervention study of sixty lactating Gambian women. The supplement contained 1000 mg Ca and was consumed between meals 5 d/week, for 1 year starting 1.5 weeks postpartum. Compliance was 100%. Plasma ferritin concentration, plasma Zn concentration and urinary Mg output were measured before, during and after supplementation at 1.5, 13, 52 and 78 weeks postpartum. No significant differences in mineral status were observed at any time between women in the supplement and placebo groups. Analysis of the longitudinal data series showed that plasma ferritin and Mg excretion were characteristic of the individual (P < 0.001). Within individuals, ferritin concentration was higher at 1.5 weeks postpartum than later in lactation (P = 0.002). Plasma Zn concentration was lower at 1.5 weeks postpartum than at other times (P < 0.001), an effect which disappeared after albumin correction. Low plasma concentrations of ferritin and Zn indicated that the Gambian women were at high risk of Fe and Zn deficiency. Measurements of alpha 1-antichymotrypsin suggested that the results were not confounded by acute-phase responses. The results of the present study indicate that 1000 mg Ca as CaCO3 given between meals does not deleteriously affect plasma ferritin and Zn concentrations or urinary Mg excretion in women who are at risk of Fe and Zn deficiency.

Measurement by radioimmunoassay of the mitochondrial uncoupling protein from brown adipose tissue of obese (ob/ob) mice and Zucker (fa/fa) rats at different ages

The concentration of the ‘uncoupling protein’ in brown adipose tissue mitochondria has been measured in lean and obese (ob/ob) mice and Zucker (fa/fa) rats at different ages using a specific radioimmunoassay. During the suckling period the concentration of the protein was similar in normal and mutant animals of both types, despite the decrease in mitochondrial GDP binding observed in the obese. The concentration of uncoupling protein was, however, decreased in adult ob/ob mice and adult Zucker rats compared with their respective lean siblings, in parallel with the decrease in GDP binding. It is concluded that there is a ‘masked’, or inactive, form of uncoupling protein in young ob/ob mice and fa/fa rats.

Decreased Brown Adipose Tissue Thermogenic Activity Following a Reduction in Brain Serotonin by Intraventricular p-Chlorophenylalanine

The effects of reducing brain serotonin (5-HT) levels by means of intracerebral-ventricular injections of the tryptophan antagonist p-chlorophenylalanine (PCPA) were investigated in male rats. Six days after the operation, PCPA-treated rats, either fedad libitum or pair-fed to the food intake of control rats, showed decreased thermogenic activity and capacity in their interscapular brown adipose tissue (BAT) and also increased fat storage in their white adipose tissue (WAT). These results indicate that serotonergic synapses might play a regulatory role in the sympathetic control of BAT thermogenesis and in the rate of WAT deposition (by an as yet unidentified mechanism), in addition to their well established role in controlling food intake.