Ethnic differences in urinary calcium and phosphate excretion between Gambian and British older adults.

UNLABELLED: 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. 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. 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. 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.

Ethnic differences in calcium, phosphate and bone metabolism.

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.

Bone mineral changes after lactation in Gambian women accustomed to a low calcium intake.

BACKGROUND/OBJECTIVES: Previous studies in Gambian women with a low calcium intake have described decreases in whole-body and regional bone mineral content (BMC) and areal bone mineral density (aBMD) during the first year of lactation. The aim of this study was to examine whether these effects are reversed after lactation. SUBJECTS/METHODS: Thirty-three Gambian women who had a previous dual-energy X-ray absorptiometry (DXA) scan at 52 weeks lactation (L52) were invited to participate in a follow-up study when neither pregnant nor lactating (NPNL) for ≥3 months and/or when 52 weeks postpartum in a subsequent lactation (F52). Whole body, lumbar spine and hip bone mineral were measured by DXA. Anthropometry and dietary assessments were also conducted. Repeated-measures analysis of covariance was used to determine differences from L52 at NPNL and F52. RESULTS: Twenty-eight women were scanned at NPNL and 20 at F52. The mean±s.d. calcium intake of the 33 women at NPNL and F52 was 360±168 mg/day. BMC, aBMD and size-adjusted BMC (SA-BMC) at all sites were higher at NPNL than L52. Percent increases in SA-BMC (mean±s.e.m.) were significant (P<0.0001): whole body=2.7±0.4%; lumbar spine=4.9±1.0%; total hip=3.7±1.0%. There were no significant differences in any measurements between the two lactation time points (L52 and F52). CONCLUSIONS: This study of Gambian women with low calcium intakes demonstrates that bone mineral mobilised during lactation is recovered after lactation. Successive periods of long lactation are not associated with progressive skeletal depletion.

Acute response to oral calcium loading in pregnant and lactating women with a low calcium intake: a pilot study.

UNLABELLED: This pilot study in women from The Gambia with low habitual calcium intakes showed differences in calciotropic hormones between pregnant, lactating and non-pregnant, non-lactating women similar to those in Western women. The response to oral calcium loading indicates a high degree of calcium conservation independent of reproductive status. INTRODUCTION: In pregnancy and early lactation, parathyroid hormone (PTH) concentrations may be suppressed. Uncertainty exists about how calcium metabolism is regulated, particularly when calcium intake is low. METHODS: We investigated fasting markers of calcium metabolism and the acute calcemic and calciuric responses after an oral calcium load in 30 pregnant, lactating or non-pregnant, non-lactating (NPNL) Gambian women with low habitual calcium intakes. Women received 1 g elemental calcium (CaCO3) at 0 min. Blood was collected at -30 and 180 min. Urine was collected from -60 to 0, 0-120 and 120-240 min. Samples were analysed (blood: ionized calcium (iCa); plasma (p): total calcium (tCa), phosphate (P), creatinine (Cr), PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D), osteocalcin (OC), ß C-terminal cross-linked telopeptide of type 1 collagen (ßCTX), cyclic adenosine monophosphate (cAMP); urine (u): Ca, P, Cr, cAMP). RESULTS: Pre-loading, groups did not differ significantly in iCa, pP, uCa/Cr and uP/Cr. pOC concentrations were significantly lower and NcAMP and p1,25(OH)2D higher in pregnant women; pPTH and pßCTX in lactating women were higher than in NPNL women. Post-loading, iCa, ptCa and uCa/Cr concentrations increased; pPTH, NcAMP, ßCTX and uP/Cr decreased in all groups, but the magnitude of change did not differ significantly between groups. CONCLUSION: Differences between pregnant, lactating and NPNL Gambian women in pPTH, NcAMP and p1,25(OH)2D and bone markers were similar to Western women. However, the response to calcium loading indicates that there may be no differences in renal and intestinal calcium economy associated with reproductive status, potentially due to a high degree of calcium conservation associated with low intakes.

Calcium intake of rural Gambian infants: a quantitative study of the relative contributions of breast milk and complementary foods at 3 and 12 months of age.

BACKGROUND/OBJECTIVES: There is a paucity of information from developing countries on total calcium intake during infancy, and potential consequences for growth and bone development. DESIGN: Observational longitudinal study of rural Gambian infants (13 males and 17 females) at 3 and 12 months of age. SUBJECTS/METHODS: Breast-milk intake and calcium concentration, weighed dietary intake, anthropometry, midshaft radius bone mineral content (BMC) and bone width (BW). RESULTS: At 3 and 12 months (mean ± s.d.) calcium intake from breast milk was 179 ± 53 and 117 ± 38, and from other foods 12 ± 38 and 73 ± 105 mg/day. There was no difference in total calcium intake; 94% and 62% of calcium came from breast milk. At 3 and 12 months, weight s.d.-scores were -0.441 ± 1.07 and -1.967 ± 1.06; length s.d.-scores were -0.511 ± 1.04 and -1.469 ± 1.13. Breast-milk calcium intake positively predicted weight (P = 0.0002, P ≤ 0.0001) and length (P = 0.056, P = 0.001). These relationships were not independent of breast-milk intake, which positively predicted weight (P ≤ 0.002) and length (P = 0.06, P = 0.004). At 3, but not 12 months, weight and length correlated with total calcium intake. There were no relationships between total calcium intake and breast-milk intake with BW or BMC. CONCLUSION: The combination of low calcium intake from breast milk and complementary foods resulted in a low total calcium intake close to the estimated biological requirement for bone mineral accretion. Relationships between calcium intake and growth were largely accounted for by breast-milk intake, suggesting that low calcium intake per se was not the limiting factor in the poor growth. These findings have potential implications for deriving calcium requirements in developing countries.

Interrelation of parathyroid hormone and vitamin D metabolites in adolescents from the UK and The Gambia.

Parathyroid hormone (PTH) is used as a marker of vitamin D (VD) status. However, PTH depends on many other factors. The 24,25-dihydroxy VD (24,25VD) concentration may be a sensitive marker because its production is reduced in VD deficiency. The relationship between VD metabolites, their ratio and PTH was investigated in adolescents from the UK and The Gambia with different calcium intakes and VD status. In the UK, there was a significant positive (+ve) association between 25VD and both 1,25-dihydroxy VD (1,25VD) and 24,25VD and a negative (-ve) association with PTH. The 24,25:25VD ratio was consistent across the 25VD concentration range. There was a +ve association between PTH and 1,25:25VD, (1,25+24,25):25VD or 1,25:24,25VD, a -ve association with 24,25VD and none with 1,25VD or 24,25:25VD. Using LnPTH and 1,25:25VD ratio (but not 1,25VD:24,25VD or 25VD:24,25VD) increased uniformity between groups and strength of relationships compared to PTH and 1,25 or 25VD alone. In The Gambia, there was a significant -ve relationship between 25VD and PTH and none with 1,25VD. There was a +ve association between 1,25VD or 1,25:25VD and PTH. The more uniform prediction of PTH by the 1,25VD:25VD ratio may be because this better reflects the extent to which PTH-induced 1,25VD production can be met by VD supply. Further validation is needed.

Use of bioelectrical impedance analysis to assess body composition in rural Gambian children.

OBJECTIVE: To validate the Tanita BC-418MA Segmental Body Composition Analyser and four-site skinfold measurements for the prediction of total body water (TBW), percentage fat-free mass (%FFM) and percentage body fat (%BF) in a population of rural Gambian children. SUBJECTS/METHODS: One hundred and thirty-three healthy Gambian children (65 males and 68 females). FFM estimated by the inbuilt equations supplied with the Tanita system was assessed by comparison with deuterium oxide dilution and novel prediction equations were produced. Deuterium oxide dilution was also used to develop equations for %BF based on four-site skinfolds (biceps, triceps, subscapular and suprailiac). RESULTS: The inbuilt equations underestimated FFM compared to deuterium oxide dilution in all the sex and age categories (P<0.003), with greater accuracy in younger children and in males. The best prediction of %FFM was obtained from the variables height, weight, sex, impedance, age and four skinfold thickness measurements (adjusted R(2)=0.84, root mean square error (MSE)=2.07%). CONCLUSIONS: These data suggest that the Tanita instrument may be a reliable field assessment technique in African children, when using population and gender-specific equations to convert impedance measurements into estimates of FFM.

Bone changes after 3 mo of lactation: influence of calcium intake, breast-milk output, and vitamin D-receptor genotype.

Factors influencing the change in bone mineral after 3 mo of lactation were investigated in 47 breast-feeding mothers, 11 formula-feeding mothers, and 22 nonpregnant, nonlactating control subjects. At 6-8 wk postpartum, the breast-feeding group had a mean (+/-SD) calcium intake of 34.8+/-13.2 mmol/d and breast-milk volume, calcium concentration, and calcium output of 0.865+/-0.230 L/d, 7.41+/-1.25 mmol/L, and 6.41+/-2.00 mmol/d, respectively. There was no relation between calcium intake and any breast-milk variable. Dual-energy X-ray absorptiometry of the whole body, spine, hip, and forearm was performed at 0.5 and 3 mo. There were significant decreases in bone mineral content at the spine (3.96%; 95% CI: 4.86%, 3.06%), femoral neck (2.39%; 95% CI: 3.61%, 1.17%), total hip (1.51%; 95% CI: 2.45%, 0.60%), and whole body (0.86%; 95% CI: 1.29%, 0.43%) in breast-feeding mothers but not in formula-feeding mothers or nonpregnant, nonlactating women. These changes were not related to calcium intake, breast-milk calcium concentration, vitamin D-receptor genotype, postpartum weight change, or use of the progesterone-only contraceptive pill. After adjustment for bone area, breast-milk volume and height were identified as significant predictors at the spine, such that greater decreases were associated with taller mothers (P = 0.007) and those with greater breast-milk volume (P = 0.001). This finding suggests that the marked bone mineral changes observed in breast-feeding mothers represented a physiologic response to lactation that was independent of dietary calcium supply.

Biochemical markers of calcium and bone metabolism during 18 months of lactation in Gambian women accustomed to a low calcium intake and in those consuming a calcium supplement.

The effect of 18 months of lactation on indexes of calcium and bone metabolism was studied in 60 Gambian women accustomed to a very low calcium intake. Half the women consumed a calcium supplement from 10 days postpartum for 52 weeks (supplement, 714 mg Ca/day; total Ca intake, 992 +/- 114 mg/day), and half consumed placebo (total Ca intake, 288 +/- 128 mg/day). Fasting blood and 24-h urine samples were collected at 1.5, 13, 52, and 78 weeks of lactation and analyzed for calciotropic hormones (intact PTH, 1,25-dihydroxyvitamin D, and calcitonin), bone turnover markers (osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline), and plasma minerals (calcium and phosphate). The first months of lactation were associated with increased bone turnover and plasma phosphate, and decreased PTH and 1,25-dihydroxyvitamin D. These effects diminished by 52 weeks, although breast milk volumes remained high. The Gambians had higher PTH, 1,25-dihydroxyvitamin D, and bone formation than British women with a greater customary calcium intake. None of the biochemical indexes was affected by calcium supplementation, with the possible exception of bone alkaline phosphatase (-29% at 52 weeks; P = 0.015). These data demonstrate that lactation-associated changes in calcium and bone metabolism are physiological and are independent of dietary calcium supply in women with very low calcium intakes.

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 l(-1); placebo, 64.9 +/- 3.5 nmol l(-1); mean +/- SE) or season. The British average was lower (53.9 +/- 3.0 nmol l(-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 l(-1); placebo, 5.10 +/- 0.13 mmol l(-1); British, 6.93 +/- 0.15 mmol l(-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.

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.

PIP: During March 1990-March 1991, 60 lactating mothers were recruited into a randomized, placebo-controlled trial designed to examine the effect of calcium (Ca) supplementation on plasma zinc (Zn) and ferritin (Fe) concentrations and on magnesium (Mg) excretion during and after Ca supplementation. The women lived in Keneba and Manduar villages in rural Gambia. They consumed 1000 mg Ca or the placebo (2 tablets of dextrose) between meals 5 days/week for 12 months beginning 1-5 weeks postpartum. All women complied. At no time were there significant differences in the indices used to determine Zn, Fe, and Mg status between lactating women on Ca supplements and those receiving the placebo. In fact, the mean differences were less than 10% of the total value. Many women (33-50%), regardless of supplementation group, had a plasma Fe concentration lower than 12 mcg/l, indicating depleted Fe stores. Many women also had low plasma Zn levels. Within individuals, plasma Zn concentrations were 15% lower at day 9 than later in lactation (p 0.001), while plasma Fe levels were 10% higher (p = 0.002). Plasma Zn levels were associated with plasma albumin levels (p 0.001). When adjusted for albumin, the effect of lactation on Zn disappeared. When compared with British women, Gambian women had a lower plasma Zn concentration (p 0.001). Within individuals and after adjustment for lactation stage and for albumin, plasma Zn levels varied between seasons (i.e., hot season values higher than other seasons) (p = 0.004). Women were more likely to excrete Mg during the hot season (p 0.001). These findings indicate that ingestion of 1000 mg Ca between meals has no adverse effect on plasma Fe and Zn levels or urinary Mg excretion in women at risk of Zn and Fe deficiency.

Effect of calcium supplements and stage of lactation on the calcium absorption efficiency of lactating women accustomed to low calcium intakes.

The effect of calcium intake on the calcium absorption efficiency from 100 mL cow milk was measured in lactating Gambian mothers habituated to a low-calcium diet [mean intake 7.08 mmol (283 mg)/d], and compared with UK lactating mothers consuming high-calcium diets [mean intake 29.2 mmol (1168 mg)/d] by using a double stable-isotope technique (oral 44Ca and intravenous 42Ca). In a double-blind trial starting 9 d postpartum, Gambian mothers were given a calcium supplement [17.85 mmol (714 mg)/d] or placebo for 12 mo. At 3 and 12 mo postpartum, mean (+/- SEM) calcium absorption from isotopically enriched milk was 52.3 +/- 3.1% (n = 25) and 47.2 +/- 4.8% (n = 24) in the unsupplemented Gambian mothers and 48.8 +/- 2.8% (n = 28) and 42.9 +/- 3.7% (n = 24) in the supplemented mothers, respectively. There was no effect of supplementation or stage of lactation on the efficiency of calcium absorption. At 3 mo postpartum the UK mothers absorbed 32.2 +/- 3.8% of the isotopically enriched calcium added to milk, which was significantly less than that of the Gambian mothers (P < 0.01).

Calcium requirements of lactating Gambian mothers: effects of a calcium supplement on breast-milk calcium concentration, maternal bone mineral content, and urinary calcium excretion.

The calcium requirement for prolonged lactation was investigated in a randomized supplementation study of Gambian mothers consuming a low-calcium diet (7.1 mmol/d, or 283 mg/d). Sixty women were studied from 10 d to 78 wk of lactation, receiving calcium or placebo for the first 12 mo. The supplement increased average calcium intake by 17.9 mmol/d (714 mg/d). Supplementation had no effect on breast-milk calcium concentration or on maternal bone mineral content. Urinary calcium output was higher in supplemented than in unsupplemented mothers by 1.18 mmol/d (47 mg/d), P < or = 0.005. Longitudinal changes in urinary calcium output and bone mineral content made a substantial contribution to calcium requirements for lactation. This study suggests that, in women with low calcium intakes, there is no direct benefit from increasing calcium intake during lactation, and that physiological mechanisms operate to furnish calcium for breast-milk production.

The calcium and phosphorus intakes of rural Gambian women during pregnancy and lactation.

The Ca and P intakes of 148 pregnant and lactating women in a rural village in The Gambia, West Africa, have been estimated by direct weighing of food on a total of 4188 d. The Ca and P contents of local foods were determined by analysis of raw ingredients, snack foods and prepared dishes. Information about the contribution of mineral-rich seasonings was obtained. Efforts were made to discover unusual sources of Ca that might not be perceived as food by subject or observer. The main contributors to daily Ca intake were shown to be leaves, fish, cereals, groundnuts and local salt. Cow's milk accounted for only 5% of Ca intake. Unusual sources of Ca were discovered, namely baobab (Adansonia digitata) fruit and selected earths, but these were consumed infrequently and their contributions to Ca intakes were small. Cereals and groundnuts were the main sources of P. Ca and P intakes (mg/d) were shown to average 404 (SD 110) and 887 (SD 219) respectively. Seasonal changes in the availability of leaves, cereals and groundnuts resulted in variations in Ca and P intakes. The rainy season was associated with increased Ca intakes (by 16%) but decreased P consumption (by 15%). No difference was observed in Ca intake between pregnant and lactating women but P intake in lactation was 11% higher than that in pregnancy during the post-harvest season. The implications of these low Ca intakes require investigation.

Breast-milk fatty acids of rural Gambian mothers: effects of diet and maternal parity.

The influence of diet and maternal parity on the fatty acid composition of mature breast milk have been studied in 23 rural Gambian mothers. The subjects' habitual diet was low in fat (16% total energy), groundnuts (peanuts) constituting the principal fat source. The high abundance of oleic and linoleic acids in groundnut fat were reflected in the proportions of these fatty acids in breast milk (47.0 +/- 1.5 and 13.0 +/- 0.3 g/100 g fat, respectively), which were elevated compared with mothers in other African communities. Estimates of daily breast-milk fatty acid secretion indicated that there was little risk of essential fatty acid deficiency in Gambian infants. The proportions of fatty acids synthesized de novo (10:0, 12:0, 14:0) were less than expected from published studies of mothers consuming low-fat diets, averaging 16.8 +/- 1.4 g/100 g fat. As the study was conducted at a time of food shortage and high energy expenditure, it is argued that mobilisation of body fat during negative energy balance increased the availability of long-chain fatty acids to the breast. The proportion of endogenous fatty acids was markedly reduced in the milk of mothers of very high parity (parity 1 = 19.3 +/- 1.6 g/100 g fat; parities 10 + = 11.4 +/- 1.5 g/100 g fat; p less than 0.01). It is hypothesised that this represents an impairment of the ability to synthesise breast-milk fatty acids de novo in these mothers.

The nutritional role of breast-milk IgA and lactoferrin.

The nutritional enigma concerning the extent to which breast-milk immune proteins are digested has been investigated by measuring the intakes and faecal outputs of IgA and lactoferrin over 7 days in 10 exclusively breast-fed (BF) and 9 formula-fed (FF) fullterm infants at 6 and 12 weeks post-partum. BF outputs (mg/day) greatly exceeded FF values (p less than 0.001): at 6 weeks secretory-IgA BF = 160 +/- 28, FF = 14 +/- 2, lactoferrin BF = 14 +/- 2, FF = 0.9 +/- 0.1; at 12 weeks secretory-IgA BF = 94 +/- 17, FF = 25 +/- 5, lactoferrin BF = 7 +/- 1, FF = 1 +/- 0.3. Secretory-IgA represented 42% and 27% of BF faecal protein at 6 and 12 weeks compared with 6% for FF infants at both ages. BF secretory-IgA outputs were highly correlated with intakes (r = 0.83, p less than 0.001). IgA and lactoferrin outputs and the presence of faecal secretory-IgA fragments in BF and FF infants were influenced by defaecation rate, suggesting that partial degradation occurred in the large intestine. By 6 weeks post-partum only 1% lactoferrin and 17% secretory-IgA intakes appeared in the faeces and 95% breast-milk protein could be regarded as nutritionally available. The elevated BF outputs of IgA and lactoferrin relative to endogenous excretion suggest, however, that breast-milk may still make a considerable contribution to intestinal defence mechanisms after the neonatal period despite the small proportion of daily intake which escapes digestion. The protective action of IgA and lactoferrin may also depend on their site of degradation and the nature of fragments.