Vitamin C, Folate, and Biotin Nutrition During Prolonged Lactation

Transcription

1 Vitamins and Minerals in Pregnancy and Lactation, edited by Heribert Berger. Nestle Nutrition Workshop Series, Vol. 1. Nestec Ltd., Vevey/Raven Press, Ltd., New York Vitamin C, Folate, and Biotin Nutrition During Prolonged Lactation Leena Salmenpera, A. Siimes, Jaako Perheentupa Children's Hospital, University of Helsinki, SF-9 Helsinki, Finland An increasing trend toward prolonged breast-feeding has been observed in many industrialized countries. When the lactation period extends over many months, the total cumulative amount of different nutrients the mother excretes into milk rises significantly. If these losses are not replaced by daily dietary intake, the mother will acquire a deficiency and the quality of breast milk will be affected. Further, an important question is sensitivity of infant nutritional status to changes in the quality of breast milk and maternal nutritional status. We investigated the nutritional status of lactating mothers, and its influence on the quality of breast milk and on the nutritional status of infants in a country with high socioeconomic standards. This was revealed by individual, longitudinal follow-ups during exclusive breast-feeding, when breast milk was the infant's only source of nutrients for to 1 months and the mother had lost considerable amounts of nutrients in the to 35 liters of milk she produced. SUBJECTS AND METHODS Our group of subjects comprised mothers and their infants, delivered at Helsinki University Hospital from June through December 1981 (1). Criteria for recruitment were a healthy, nonsmoking mother with uncomplicated pregnancy and delivery; a full-term, singleton infant of weight appropriate to gestational age, with an Apgar score of 8, and no evidence of disease. The mothers were encouraged to breast-feed exclusively as long as possible. The number that succeeded decreased to 1 at months, 11 at months, 71 at 7.5 months, 3 at 9 months, and 7 at 1 months. Ten nonpregnant, nonlactating healthy Finnish women were used as a reference group. 7

2 8 NUTRITION AND PROLONGED LACTA TION Supplementation Of the mothers in the study, 7% told us that during pregnancy they had taken daily supplements comprising 75 mg vitamin C and.5 mg folate. During lactation, all the mothers took supplementary iron and vitamins, including.1 mg folate daily in accordance with recommended dietary allowances (RDA) (), but no vitamin C or biotin. Supplementation was started 5 days after delivery and continued throughout lactation. The exclusively breast-fed infants received no supplementation except vitamins A and D. Blood and Milk Samples A blood sample was taken from the umbilical vein and from the mother on the third or fourth day after delivery. Later, all mother-infant pairs were examined and samples taken at,,, 7.5, 9, 1, 11, and 1 months of lactation. Breast milk samples were taken concurrently with maternal plasma samples. Vitamin C analyses were made by collecting a fresh 5-ml milk sample in a tube containing 5 ml of 1% metaphosphoric acid. Biotin analyses were conducted after pooling 5 ml samples of milk taken before and after each feed over a -hr period. Vitamin C plasma samples were stabilized and deproteinized by adding metaphosphoric acid. All plasma and milk samples were immediately frozen and kept at - 18 C. Analytical Methods All vitamin analyses were carried out in the Department of Vitamin and Nutrition Research, F. Hoffmann-La Roche & Co, Basel, Switzerland. Vitamin C concentrations were analyzed by microfluorometric assay (3). Concentrations <. mg/1 ml indicate a high risk of deficiency and >. ing/1 ml adequate nutrition. The plasma concentrations of total folate were determined by radioimmunoassay (Diagnostic Products Corporation, Los Angeles, California) after being released from proteins. The reference values for this method are from 3 to 15 jig/liter. The total biotin concentration was quantified microbiologically {Lactobacillus plantarum, ATCC 81) after digestion with papain (). The reference values range from 7 to 1,15 ng/ liter. ANALYSIS OF DIETARY INTAKE In accordance with instructions given by a dietitician, 7 of the lactating mothers kept a 7-day record of their food consumption at and months

3 NUTRITION AND PROLONGED LACTA TION 9 TABLE 1 Months Milk volume Mean volume postpartum N (ml) (ml/day) ml/kg/day postpartum (5). The records were analyzed by a computer program to give the average daily intake of vitamin C (). The mothers weighed their infants at home before and after each feed during a 7-hr period. The daily milk volumes, calculated as a mean for these 3 days, are summarized in Table 1. Statistical Analysis Data were analyzed with BMDP software by the University of California, Los Angeles (7). The folate and biotin concentrations were log-normally distributed. We used the analysis of variance for repeated measurements in the longitudinal evaluation and the chi-square test for estimating the frequency of subnormal concentrations, simple linear regression, and correlation analysis. VITAMIN C Vitamin C concentrations in breast milk appear to be affected by the vitamin status of the mother (8). The milk concentration can be raised by increasing the mother's vitamin C intake (8-1); however, there seems to be a saturation level (8,11-13). Supplementation of well-nourished women with vitamin C does not increase these concentrations (13). The vitamin C concentrations in breast milk are known to decrease over the course of lactation (8,1). Our results (15) confirm earlier reports, in that milk concentration decreased during lactation (Fig. 1). The maternal plasma concentrations correlated with the milk concentrations (Fig. ). The maternal vitamin C intake correlated with the plasma concentration (Fig. 3) and with the milk concentration (/ =.3; p =.1). The dietary intake of vitamin C was generally high, the mean value being 138 mg/day. Of 7 mothers, six, however, had intakes below the RDA for lactating mothers (1 mg/day) during both surveys (). In three of these

4 5 NUTRITION AND PROLONGED LACTATION 3 9 MONTHS OF LACTATION FIG. 1. Concentrations of vitamin C during exclusive breast-feeding. Values for maternal plasma (lowest curve); infant piasmaand milk (uppermost curve). The broken curve shows the plasma values of the formula-fed infants; mean ± SEM. [From Salmenpera (15).] 5 r=.59 p<.1 i.. I.,. I i, r=.75 p<.1 i i. 1 i c i I,, * 1 1 MATERNAL VITAMIN C. mg/looml * r=. p<.1.,, 1,,, 1,, r=.7 p<.1 FIG.. Correlation between concentrations of vitamin C in maternal plasma and breast milk during exclusive breast-feeding.

5 NUTRITION AND PROLONGED LACTATION 51 E AT MONTHS AT MONTHS o _- r=.38 - r=.1 p=. p<.1 < cr y- z LU CJ O U CO Tl m /.. jy ~ jt ft y / " ' ~ VITAMIN C INTAKE, mg/day FIG. 3. Correlations between daily vitamin C intakes and maternal plasma concentrations at and months of lactation. mothers, plasma concentrations <. mg/1 ml were found on up to three occasions during the follow-up (Table ). None of them showed signs of vitamin deficiency. During the first months of lactation, mean maternal vitamin C concentration was lower than that of nonlactating Finnish women (1. mg/1 ml). During feeding on breast milk alone, a total of 73 maternal plasma samples were taken, of which 9 (in individual mothers) showed a concentration indicating a high risk of vitamin C deficiency. The highest number of such samples occurred months postpartum and during spring. In two mothers the concentration was <. mg/1 ml for to months without overt signs of deficiency. Only one infant had a vitamin C concentration <. mg/1 ml while fed exclusively on breast milk. Her mother's plasma concentration had been low for preceding months owing to a sudden decreased intake of the vitamin. (Table 1, case 1). The mother began a strict diet devoid of fresh fruit and vegetables due to an eruption of atopic eczema. Other infants of mothers with low plasma concentrations had adequate plasma concentrations themselves. In general, the infant plasma concentrations of vitamin C showed no correlation with those of the breast milk, with total intakes of the vitamin, or with maternal plasma concentrations. FOLATE The reported values for folate concentrations in milk vary widely (9,11,1,17); there are many reasons for this. Some reports deal with total

6 5 NUTRITION AND PROLONGED LACTATION TABLE. Vitamin C intake of 7 mothers anaiyzed at and months of lactation' Case Month of lactation Daily vitamin C intake (mg/day) Vitamin C concentration (mg/1 ml) Maternal plasma Milk Infant plasma < Mean of all cases In seven cases the intake was low (<1 mg/day). These cases are described in detail: individual intakes, maternal plasma, milk concentrations, and infant plasma concentrations during exclusive breast-feeding; the low values are in italics.

7 NUTRITION AND PROLONGED LACTATION 53 folate concentrations and some with free folate concentrations; the method of sample collection also accounts for some variability; and the samples obtained early in lactation, in the morning, or at the beginning of a feed underestimate the folate concentration (18). Moreover, labile folate in milk is easily destroyed. The concentrations in milk appear to be affected by the folate status of the lactating mother (9,1,19), but, as in the case of vitamin C, there seems to be a saturation level (11,1,17); supplementation of well-nourished women does not increase the folate concentration in milk. However, lactation tends to deplete maternal folate stores () and may even lead to megaloblastic anemia (1). The milk concentration is reported to increase during the first months of lactation (18,19) and subsequently to plateau (1). In our study we were unable to measure milk folate concentrations, but we could monitor the individual maternal and infant plasma concentrations (). Gestational folate supplementation led to increased folate concentrations in maternal and umbilical vein plasma, but there were no differences in the anthropometric measurements of the newborn, whether the mother had taken folate supplementation during pregnancy or not. Of 18 unsupplemented mothers, three had signs of macrocytic anemia (hemoglobin < 15 g/liter; MCV > 9 fl), although their plasma concentrations of both folate and vitamin Bi were adequate when measured 3 to days postpartum. Further, there were six mothers in whom the anemia might in part be due to folate deficiency (Table 3). The positive effect of the gestational supplement was apparent up to to 9 months postpartum; the geometric mean concentration was higher (Fig. ), and the number of the samples with inadequate concentrations was lower in the supplemented than in the unsupplemented mothers (Table ). During lactation all mothers were given supplementary folate. Their mean plasma concentration was similar to or higher than that of 5. jig/liter in a group of nonlactating Finnish women; however, there were 19 individual TABLE 3. Postpartum values of mothers with blood hemoglobin concentration <15 g/liter and plasma folate concentration <3 \y.g/liter* Hemoglobin (g/liter) MCV (fl) Folate (p.g/liter) Vitamin B1 (ng/liter) Ferritin (Mfl/llter) Normal values: >15 g/liter; fl; >3 fig/liter; > ng/liter; > M-g/liter. * None of these mothers had vitamin supplements during pregnancy.

8 5 NUTRITION AND PROLONGED LACTATION 5 ui -H LU o < 15 1 FIG.. Plasma folate concentrations (geometric means ± SEM) In lactatlng mothers (lower curves) and their infants (upper curves) during exclusive breast-feeding from birth to 1 months. The mothers received.1 mg folate supplement daily; (solid curves) gestational folate supplement (.5 mg daily); (broken curves) no gestational folate supplement. [From Salmenpera ().] MONTH OF LACTATION mothers with concentrations ^3 ^.g/liter (in two for a period over months without signs of deficiency in red cell indices). During exclusive breast-feeding, all infants had high folate plasma concentrations. At and after age months, the infant plasma concentrations were similar, regardless of whether or not the mother had taken a supplement TABLE. Frequency (%) of inadequate (<&3. ^g/liter) and adequate (>5. ^g/liter) maternal plasma folate concentrations during exclusive breast-feeding among mothers without and with gestational folate supplement (.5 mg daily)' =S3 (xg/liter >5 (xg/liter Month of lactation" Without supplement With supplement Without supplement With supplement P d T < " From Salmenpera () b All mothers were given supplementary folate (.1 mg daily) during lactation. e n = 1. d Chi-square test.

9 NUTRITION AND PROLONGED LACTATION 55 AT BIRTH AT AGE MONTHS AT AGE 9 MONTHS 3. U> t z < LU < 5 _ 3 d is _ I.. / - "v **>< -.*.** r-.1 p<.1 *.'.f* r=.35 p=. * * S^ **» ' PLASMA FOLATE OF MOTHERS, Jjg/1 m r=.5 p=.,,, 1,,. 1,,, FIG. 5. Correlation between infant and maternal plasma folate concentrations at birth and at and 9 months of exclusive breast-feeding. At,, and 7i months, there was no correlation. [From Salmenpera ().] during pregnancy (Fig. ). Some correlation between maternal and infant plasma concentrations of folate was determined at birth, as well as after and 9 months of lactation (Fig. 5). BIOTIN Similar to the case of vitamin C and folate, biotin concentrations in breast milk seem to be affected by poor nutritional status of the mother (9), but supplementation of well-nourished mothers provides no advantage (3). During the first days of lactation, biotin is almost completely absent, even from milk of well-nourished mothers (). In the mothers we studied (5), the mean plasma concentration of biotin was lower on day 3 or postpartum than during lactation (3 ng/liter) or than in a group of nonlactating Finnish women (31 ng/liter) (Fig. ). A concentration < ng/liter was found in % of the samples at delivery and in 1% later throughout lactation. Similar low concentrations have been reported in up to 1% of blood samples taken from Swiss mothers during delivery (); however, during the longitudinal follow-up, plasma concentrations of the individual mothers varied greatly (Fig. 7), and none had low concentration for prolonged periods. The mean concentration of biotin in breast milk was 15 times higher than the corresponding mean maternal plasma concentration. The maternal plasma and milk concentrations correlated during,, and months of lactation (Fig. 7).

10 5 NUTRITION AND PROLONGED LACTATION 1, CT 5- c o I I I < I -z. LJJ 5-1- MILKS O 5 o O n m 5 I 1 t 3 9 MONTH OF LACTATION SERA 1 FIG.. Biotin concentrations in milk (upper curve) and plasma samples (lower curve) from lactating mothers followed for 1 months after delivery. The number of participants decreased gradually from to 7. Geometric mean values ± SD are given. [From Salmenpera (5).] z" 15 o 3 io i=! 5. r=. p=. 3r''" 1 1 * r=. p<.1 I r=.3 p=.. I. jiff.'. ^r i.,, i i,,, 1, i,,, i, PLASMA BIOTIN CONCENTRATION, ng/1 *. '."".' *. r=.7 p=.7 i,,, i 5 5 FIG. 7. Correlations between maternal plasma and milk concentrations of biotin at,,, and 9 months of lactation. [From Salmenpera (5).]

11 CONCLUSIONS NUTRITION AND PROLONGED LACTATION 57 During to 1 months of lactation, the mothers excreted into milk 1 to 71 mg vitamin C daily and to 1 jxg biotin (Table 5). The mean (±SD) daily loss of folate has been estimated to be 5.5 ± 3 xg (1) at 1 weeks of lactation or to range from 57 to 15 fig (17) during lactation. This means that during months lactation, a mother loses on the average 7.5 g vitamin C, 9 mg folate, and 5 fxg biotin. The minimum requirement of vitamin C during lactation can be estimated by adding the known minimum daily antiscorbutic dose, 1 mg/day (), to the daily amount excreted in milk. Calculated on the basis of present data, this is from 3 to 7 mg. The daily saturation requirement is higher, i.e., 1 mg/day (), which means that optimal intake during lactation would be about 1 to 17 mg/day. In Finland the increased requirement during lactation is met by proper diet. The minimum daily requirement of folate is considered to be 5 u.g and the saturation requirement to be 1 to xg (). Thus, the minimum requirement during lactation is 1 to (xg/day and the optimal requirement about 15 to 35 (xg/day. This means that the total folacin activity in the diet should be as high as 3 to 7 u,g/day, because only 5% to 5% dietary folacin is nutritionally available (). The daily intake of folate varies greatly in different countries (). The data from Scandinavia indicate that the median intake for women is between 8 and 17 (xg/day (8,9). This means that the requirement for folate during lactation is increased to an extent that is not always met by the diet. The clinical significance of low biotin levels is not yet clear (7). At all events, lactation did not increase the risk of low plasma concentrations in Finnish women. Mean concentrations, like all cross-sectional data, are of limited value in assessing the nutritional status or need for supplementation. Optimal or even high mean values may conceal individuals with poor nutriture. A good example of this was the vitamin C levels in Finnish lactating mothers. Despite TABLE 5. Maternal losses in vitamin C and biotin during exclusive breast-feeding; median and range Month of lactation (n) Nutrient (1) (3) 9 (1) 1-1 (19) Vitamin C mg/day Biotin ng/day

12 58 NUTRITION AND PROLONGED LACTATION a good mean value of daily dietary intake, there were some mothers with inadequate intake, leading to low plasma concentrations over prolonged periods. Further, we emphasize that both maternal plasma and milk concentrations seemed to be channeled, some individuals having low (or high) concentrations in most samples compared with the mean concentration. This means that some mothers have low plasma concentrations for long periods, and the risk of deficiency is higher than with one temporarily low value. This channeling in milk concentrations ends in similar long-term variation in daily intake levels of infants. The channeling was observed in the maternal vitamin C and folate plasma concentrations and in the milk vitamin C concentrations, but not in the biotin concentrations. Despite this channeling, however, the infants were able to maintain adequate plasma vitamin C and folate concentrations, which were much higher than the maternal concentrations. ACKNOWLEDGMENTS This study was supported by grants from the Sigrid Juselius Foundation as well as by Foundations for Pediatric and Nutritional Research. We also acknowledge the help provided by the Department of Vitamin and Nutrition Research, F. Hoffmann-La Roche & Co, Basel, Switzerland. REFERENCES 1. Salmenpera L, Perheentupa J, Siimes MA. Exclusively breast-fed healthy infants grow slower than reference infants. Pediatr Res 1985;19: Food and Nutrition Board, National Research Council, Recommended dietary allowances. 9th ed. Washington, DC: National Academy of Sciences, Deutsch MJ, Weeks CEJ. Microfluorometric assay for vitamin C. JAssoc Offic Agric Chem 195 ;8: Frigg M, Brubacher G. Microbiological method with Lactobacillus plantarum. Int J Vitam NutrRes 197;: Pekkarinen M. Methodology in the collection of food consumption data. World Rev Nutr Diet 197;1: Ahlstrom A, Rasanen L, Kuvaja K. A method of data processing for food-consumption surveys. Ann Acad Sci Fenn (Biol) 197;19:l Dixon WJ. BMDP Statistical software Berkeley, California: Department of Biomathematics, University of California Press, Irwin MI, Hutchins BK. A conspectus of research on vitamin C requirements in man. J Nutr 197;1: Deodhar AD, Rajalakshmi R, Ramakrishnan CV. Studies on human lactation. Part III. Effect of dietary vitamin supplementation on vitamin contents of breast milk. Ada Paediatr Scand 19;53: Tarjan R, Kramer M, Szoke K, Lindner K. The effect of different factors on the composition of human milk and its variations. I. The effect of vitamin-rich foods on the composition of human milk. Nutr Dieta 193;5: Lonnerdahl B. Effects of maternal dietary intake on human milk composition. J Nutr 198;11: Sneed SM, Zane C, Thomas MR. The effect of ascorbic acid, vitamin B, vitamin B l and

13 NUTRITION AND PROLONGED LACTA TION 59 folic acid supplementation on the breast milk and maternal nutrition status of low socioeconomic lactating women. Am J Clin Nutr 1981 ;3: Thomas MR, Sneed SM, Wei C, Nail PA, Wilson M, Sprinkle EE. The effects of vitamin C, vitamin B. vitamin B 1, folic acid, riboflavin, and thiamine on the breast milk and maternal status of well-nourished women at months postpartum. Am J Clin Nutr 198;33: Karra MV, Udipi SA, Kirksey A, Roepke JLB. Changes in specific nutrients in breast milk during extended lactation. Am J Clin Nutr 198;3: Salmenpera L. Vitamin C nutrition during prolonged lactation: Optimal in infants while marginal in some mothers. Am J Clin Nutr 198;: Smith MA, Picciano MF, Deering RH. Folate supplementation during lactation: Maternal folate status, human milk folate content, and their relationship to infant folate status. J Pediatr Gastroenterol Nutr 1983;: Tamura T, Yoshimura Y, Arakawa T. Human milk folate and folate status in lactating mothers and their infants. Am J Clin Nutr 198;33: Brown CM, Smith AM, Picciano MF. Forms of human milk folacin and variation patterns. J Pediatr Gastroenterol Nutr 198;5: Cooperman JM, Dweck HS, Newman LJ, Garbarino C, Lopez R. The folate in human milk. Am J Clin Nutr 198;3: Metz J. Folate deficiency conditioned by lactation. Am J Clin Nutr 197;3: Shapiro J, Alberts HW, Welch P, Metz J. Folate and vitamin Bi deficiency associated with lactation. Br J Haematol 195;ll: Salmenpera L, Perheentupa J, Siimes MA. Folate nutrition is optimal in exclusively breastfed infants but inadequate in some of their mothers and in formula fed infants. J Pediatr Gastroenterol Nutr 198;5: Pratt JP, Hamil BM, Moyer EZ, et al. Metabolism of women during the reproductive cycle. XVIII. The effect of multivitamin supplements on the secretion of B vitamins in human milk. J Nutr 1951 ;: Bonjour JP. Biotin in man's nutrition and therapy a review. Int J Vitam Nutr Res 1977;7: Salmenpera L, Perheentupa J, Pispa JP, Siimes MA. Biotin concentrations in maternal plasma and milk during prolonged lactation. Int J Vitam Nutr Res 1985:55: Dostalova L. Correlations of the vitamin status between mother and newborn during delivery. Dev Pharmacol Ther 198;(suppl): Bonjour J. Biotin in human nutrition. Ann NYAcad Sci 1985;7: Elsborg L, Rosenquist A. Folate intake by teenage girls and by pregnant women. Int J Vitam Nutr Res 1979;9: Jagerstad M. Folsyra-absorptionen. Lakartidningen 1975;7:31-.