Abstract
We investigated whether supplementation of regular formula (RF) with cholesterol (Ch) (RF+Ch) influenced circulating Ch levels and de novo synthesis compared with their breast-fed (BF) counterparts in 4-mo-old infants. The incorporation rate of deuterium in body water into erythrocyte membrane-free Ch over 48 h was used as an index of cholesterogenesis. Plasma total-Ch and LDL-Ch concentrations were highest(p < 0.02) in BF infants, compared with infants in the RF-fed groups. Infants in the RF+Ch groups showed an intermediate response; their plasma total-Ch and LDL-Ch concentrations were not significantly different from the BF or the RF-fed groups. Plasma total/HDL-Ch and LDL/HDL-Ch ratios were higher (p < 0.05) in BF, and higher in RF+Ch-fed infants, compared with those fed RF, whereas not different between BF and RF+Ch-fed infants. At 4 mo of age, Ch FSR was 4-fold lower(p < 0.0001) in BF versus other groups, but not significantly different between RF- and RF+Ch-fed infants. Thus, despite addition of Ch to the concentration found in breast milk, FSR remained elevated compared with that of the group fed breast milk, with an intermediate response in circulating Ch levels. It is speculated that factors other than Ch intake account for the differential Ch metabolism between formula-fed and BF infants.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- RF :
-
regular formula
- Ch :
-
cholesterol
- BF :
-
breast-fed
- FSR :
-
fractional synthetic rate
References
Carlson SE 1991 Plasma cholesterol and lipoprotein levels during fetal development and infancy. Ann NY Acad Sci 623: 81–89.
Jooste PL, Rossouw LJ, Steenkamp HJ, Rossouw JE, Swanepoel ASP, Charlton DO 1991 Effect of breast-feeding on the plasma cholesterol and growth of infants. J Pediatr Gastroenterol Nutr 13: 139–142.
Innis SM, Hamilton JJ 1992 Effects of developmental changes and early nutrition on cholesterol metabolism in infancy. J Am Col Nutr 11: 63S–68S.
Kali MJT, Salmenpera L, Siimes MA, Perheentupa J, Miettinen TA 1992 Exclusive breast-feeding and weaning: effect on serum cholesterol and lipoprotein concentration in infants during the first year of life. Pediatrics 89: 663–666.
Wong WW, Hachey DL, Insull W, Opeckun AR, Klein PD 1993 Effect of dietary cholesterol on cholesterol synthesis in breast-fed and formula-fed infants. J Lipid Res 34: 1403–1411.
Cruz MLA, Wong WW, Mimouni F, Hachey DL, Setchell KDR, Klein PD, Tsang R 1994 Effects of infant nutrition on cholesterol synthesis rates. Pediatr Res 35: 135–140.
Boehm G, Moro G, Muller DM, Muller H, Raffler G, Minol I 1995 Fecal cholesterol excretion in preterm infants fed breast milk of formula with different cholesterol contents. Acta Pediatr 84: 240–244.
Mize CE, Uauy R, Kramer R, Benser M, Allen S, Grundy SM 1995 Lipoprotein-cholesterol responses in healthy infants fed defined diets from ages 1 to 12 months: comparison of diets predominant in oleic acidversus linoleic acid, with parallel observations in infants fed a human milk-based diet. J Lipid Res 36: 1178–1187.
Friedman G, Goldberg SJ 1975 Concurrent and subsequent serum cholesterols of breast- and formula-fed infants. Am J Clin Nutr 28: 42–45.
Huttenen JK, Saarinen UM, Kostiainen E, Siimens MA 1983 Fat composition of the infant diet does not influence subsequent serum lipid levels in man. Atherosclerosis 46: 87–94.
Fall CH, Barker DJ, Osmond C, Winter PD, Clark PM, Hales CN 1992 Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease. BMJ 304: 801–805.
Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME 1989 Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 298: 564–567.
Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ 1989 Weight in infancy and death from ischaemic heart disease. Lancet 2: 577–580.
Fomon SJ, Rogers RR, Ziegler EE, Nelson SE, Thomas LN 1984 Indices of fatness and serum cholesterol at eight years in relation to feeding and growth during early infancy. Pediatr Res 18: 1233–1238.
Wagner V, von Stockhausen HB 1988 The effect of feeding human milk and adapted milk formulae on serum lipids and lipoprotein levels in young infants. Eur J Pediatr 147: 292–295.
Hodgson PA 1976 Comparison of serum cholesterol in children fed high, moderate, or low cholesterol milk diets during the neonatal period. Metabolism 25: 739–746.
Marmont MG, Page CM, Atkins E, Douglas JWB 1980 Effect of breast-feeding on plasma cholesterol and weight in young adults. J Epidemiol Community Health 34: 164–167.
Watkins JB, Jarvenpaa A-L, Szczepanik-Van Leeuwen PA, Klein RD, Rassin DK, Gaull G, Raiha, NCR 1983 Feeding the low birth weight infant. V. Effects of taurine, whole sterol, and human milk on bile acid kinetics. Gastroenterology 85: 793–800.
Jarvenpaa AL, Raiha NCR, Rassin DK, Gaull GE 1983 Feeding the low-birth-weight infant. I. Taurine and cholesterol supplementation of formula does not affect growth and metabolism. Pediatrics 71: 171–178.
Van Biervliet J-P, Vinaimont N, Vercaemst R, Rosseneu M 1992 Serum cholesterol, cholesteryl ester, and high-density lipoprotein development in newborn infants: response to formula supplemented with cholesterol and gamma-linoleic acid. J Pediatr 120: S101–S108.
Rassin DK, Gaull GE, Jarvenpaa A-L, Raiha NC 1983 Feeding of the low-birth-weight infants. II. Effect of taurine and cholesterol supplementation on amino acids and cholesterol. Pediatrics 71: 179–186.
Friedewald RT, Levy RI, Frederickson P 1972 Estimation of the concentration of low density lipoprotein concentration without use of preparative ultracentrifuge. Clin Chem 18: 499–502.
Purvis GA, Bartholmey S 1988 Infant feeding practices commercially prepared baby foods. In: Tsang RC, Nichols BL (eds) Nutrition during Infancy. Hanley Belfus, Philadelphia, 399–417.
Jones PJH, Leitch CA, Li ZC, Connor WE 1993 Human cholesterol synthesis measurement using deuterated water: theoretical and procedural considerations. Arterioscler Thromb 13: 247–253.
Zar BH 1984 Biostatistical Analysis, 2nd Ed. Prentice-Hall, Englewood Cliffs, NJ, pp
Lubchenco LO, Hansman C, Boyd E 1966 Intrauterine growth in length and head circumference. Pediatrics 37: 403–408.
Grundy SM, Ma D 1990 Dietary influences on serum lipids and lipoproteins. J Lipid Res 31: 1149–1172.
Mazier MJ, Jones PJH 1997 Diet fat saturation and feeding state modulate rates of cholesterol synthesis in normo-lipidemic men. J Nutr 127: 332–340.
Turley SD, West CE 1976 Effect of cholesterol and cholestryamine feeding and of fasting on sterol synthesis in the liver, ileum, and lung of the guinea pig. J Lipids 11: 571–577.
Shady DK, Deutsche JM 1988 Interaction of dietary cholesterol and triglyceride in the regulation of hepatic low density lipoprotein transport in the hamster. J Clin Invest 81: 300–309.
Jones PJH, Hrboticky N, Hahn P, Innis SM 1990 Comparison of breast-feeding and formula-feeding on intestinal and hepatic cholesterol metabolism in neonatal pigs Am J Clin N. utr 51: 979–984.
Nestel PJ, Poyser A 1976 Changes in cholesterol synthesis and excretion when cholesterol intake is increased. Metabolism 25: 1591–1599.
McNamara DJ, Kolb R, Parker TS, Batwin H, Samuel P, Brown CD, Ahrens EH Jr 1987 Heterogeneity of cholesterol homeostasis in man: response to changes in dietary fat quality and cholesterol quantity. J Clin Invest 79: 1729–1739.
Jones PJH, Pappu AS, Hatcher L, Li ZC, Illingsworth DR, Connor WE 1996 Dietary cholesterol feeding suppresses human cholesterol synthesis measured by deuterium incorporation and urinary mevalonic acid levels. Arterioscler Thromb Vasc Biol 16: 10–16.
Wilson JD, Lindsey CA 1965 Studies on the influence of dietary cholesterol on cholesterol metabolism in steady state in man. J Clin Invest 44: 1805–1814.
Grundy SM, Ahrens EH, Davignon J 1969 The interaction of absorption and cholesterol synthesis in man. J Lipid Res 10: 304–315.
Jones PJH, Lichtenstein AH, Schaefer EJ 1994 Interaction of dietary fat saturation and cholesterol level on cholesterol synthesis measured using deuterium incorporation. J Lipid Res 35: 1093–1101.
Chen IS, Hotta SS, Ikeda I, Cassidy MM, Shepard AJ, Vahouny GV 1987 Digestion, absorption and effects on cholesterol absorption of menhaden oil, fish oil concentrate and corn oil by rats. J Nutr 117: 676–680.
Kamei M, Ohgaki S, Kanbe T, Niiya I, Mizutani H, Matsui-Yuasa I, Otani S, Morita S 1995 Effects of highly hydrogenated soybean oil and cholesterol on plasma, liver cholesterol, and fecal steroids in rats. Lipids 30: 533–539.
Thomson AB, Keelan M, Llam T, Rajotte RV, Garg ML, Clandinin MT 1993 Fish oil modifies effects of high cholesterol diet on intestinal absorption in diabetic rats. Diabetes Res 22: 171–183.
Thomson AB, Keelan M, Cheng T, Clandinin MT 1993 Delayed effects of early nutrition with cholesterol plus saturated or polyunsaturated fatty acids on intestinal morphology and transport function in the rat. Biochim Biophys Acta 1170: 80–91.
Berr F, Goetz A, Schreiber E, Paumgartner G 1993 Effects of dietary n-3 versus n-6 polyunsaturated fatty acids on hepatic excretion of cholesterol in the hamster. J Lipid Res 34: 1275–1284.
Kushwaha, RS, Rice KS, Lewis DS, McGill HC Jr, Carey KD 1993 The role of cholesterol absorption and hepatic cholesterol content in high and low responses to dietary cholesterol and fat in pedigreed baboons. Metabolism 42: 714–722.
Meijer, GW, Lemmens AG, Versluis A, Van Zutphen LF, Beynen AC 1991 The hyper-cholesterolemic effect of dietary coconut fatversus corn oil in hypo- or hyperresponsive rabbits is not exerted through influencing cholesterol absorption. J Lipid Res 1980: 699–713.
Goodman DS, Smith FR, Seplowitz AH, Ramakrishnan R, Dell RB 1980 Prediction of the parameters of whole body cholesterol metabolism in humans. J Lipid Res 21: 699–713.
Grundy, SM 1983 Absorption and metabolism of dietary cholesterol. Ann Rev Nutr 983: 71–76.
Zilversmit DB 1973 A proposal linking atherogenesis to the interaction of endothelial lipoprotein lipase with triglyceride-rich lipoproteins. Circ Res 33: 633–638.
Samuel P, McNamara DJ 1983 Differential absorption of exogenous and endogenous cholesterol in man. J Lipid Res 24: 265–276.
Miettinen TA, Kesaniemi YA 1989 Cholesterol absorption: regulation of cholesterol synthesis and elimination and within-population variations of serum cholesterol levels. Am J Clin Nutr 49: 629–635.
Jandacek RJ, Ramirez MM, Crouse JR 1990 Effects of partial replacement of dietary fat by olestra on dietary cholesterol absorption in man. Metabolism 39: 848–852.
Van Lier JE, Smith LL 1969 Chromatography of some cholesterol autoxidation products on Sephadex. J Chromatogr 41: 37–42.
Jensen RG 1989 The Lipids of Human Milk. CRC Press, Boca Raton, FL, 187–192.
Bitman J, Wood DL, Mehta NR, Hamosh P, Hamosh M 1986 Comparison of the cholesteryl ester composition of human milk from preterm and term mothers. J Pediatr Gastroenterol Nutr 5: 780–786.
Jones PJH, Scanu AM, Schoeller DA 1988 Plasma cholesterol synthesis using deuterated water in humans: effect of short-term food restriction. J Clin Lab Med 111: 627–633.
Wong WW, Hachey DL, Feste A, Leggit J, Clarke LL, Pond WG, Klein PD 1991 Measurement of in vivo cholesterol synthesis form 2H2O: a rapid procedure for the isolation, combustion, and isotopic assay of erythrocyte cholesterol. J Lipid Res 32: 1049–1056.
Jones PJH, Lichtenstein, AH, Schaefer EJ 1994 Interaction of dietary fat saturation and cholesterol level on cholesterol synthesis measured using deuterium incorporation. J Lipid Res 35: 1093–1101.
Gamble JL, Blackfan K 1920 Evidence indicating a synthesis of cholesterol by infants. J Biol Chem 1920: 42:4401-409
Huang CTL, Rodriguez JT, Woodward WE, Nichols B 1976 Comparison of patterns of fecal bile acid and neutral sterols between children and adults. Am J Clin Nutr 29: 1196–1203.
Potter JM, Nestel P 1976 Greater bile acid excretion with soy bean than with cow milk in infants. Am J Clin Nutr 29: 546–551.
Nestel PJH, Poser A, Bolton T 1979 Changes in cholesterol metabolism in infants in response to dietary cholesterol and fat. Am J Clin Nutr 32: 2177–2182.
Ferezou J, Rautueau J, Coste T, Gouffier E, Chevalier F 1983 Cholesterol turnover in human plasma lipoproteins: studies with stable and radioactive isotopes. Am J Clin Nutr 36: 235–244.
Dell RB, Ramakrishnan R, Palmer RH, Goodman DS 1985 A convenient six-point blood sampling schedule for determining whole body cholesterol kinetics in humans. J Lipid Res 26: 575–582.
Schwartz CC, Zech LA, VandenBroek JM, Cooper PS 1993 Cholesterol kinetics in subjects with bile fistula: positive relationship between size of the bile acid precursor pool and bile acid synthetic rate. J Clin Invest 91: 923–938.
London IM, Schwartz H 1953 Erythrocyte cholesterol: the metabolic behaviour of the cholesterol of human erythrocytes. J Clin Invest 32: 1248–1252.
Dietschy JM, Spady DK 1984 Measurement of rates of cholesterol synthesis in vivo using tritiated water. J Lipid Res 25: 1469–1476.
Jones PJH 1990 Use of deuterated water for measurement of short-term cholesterol synthesis in humans. Can J Physiol Pharmacol 68: 955–959.
Jones PJH, Ausman LM, Croll DH, Feng JY, Schaefer EA, Lichtenstein AH 1998 Validation of deuterium incorporation against sterol balance for measurement of human cholesterol biosynthesis. J Lipid Res (in press)
Schwartz CC, Vlahcevic ZR, Berman M, Meadows J 1965 Central role of high density lipoprotein in plasma free cholesterol metabolism. J Clin Invest 70: 105–116.
Jones PJH, Schoeller DA 1990 Evidence for diurnal periodicity in human cholesterol synthesis. J Lipid Res 31: 667–673.
Leitch CA, Jones PJH 1991 Measurement of triglyceride synthesis in humans using deuterium oxide and isotope ratio mass spectrometer. Biol Mass Spectrom 20: 392–396.
Jones PJH, Leitch CA, Pederson RA 1993 Meal-frequency effects on plasma hormone concentrations and cholesterol synthesis in humans. Am J Clin Nutr 57: 868–874.
Hachey DL, Wong WW, Pond W, Clark L, Llaurador M, Klein P 1992 Cholesterol synthesis in genetically lean and obese piglets on either low or high cholesterol diets. FASEB J 6: 1091
DeLucchi C, Pita ML, Periago JL, Gil, A 1988 Influences of diet and postnatal age on the lipid composition of red blood cell membrane in newborn infants. Ann Nutr Metab. 32: 231–239.
Putnam JC, Carlson SE, DeVoe PW, Barness, L 1983 The effect of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants. Am J Clin Nutr 36: 106–114.
Cai H-J, Xie C-L, Chen Q, Chen X-Y, Chen Y-H 1991 The relationship between hepatic low-density lipoprotein receptor activity and serum cholesterol level in the human fetus. Hepatology 13: 852–857.
Uauy, R, Mize C, Grundy S 1989 Effect of early diet on plasma lipoproteins (L) and LDL receptor activity at 1 year of age. Pediatr Res 25: 126A
Author information
Authors and Affiliations
Additional information
Supported by the American Heart and Stroke Foundation, the Cincinnati Children's Hospital Clinical Research Center, and Wyeth-Ayerst Laboratories.
Rights and permissions
About this article
Cite this article
Bayley, T., Alasmi, M., Thorkelson, T. et al. Influence of Formula versus Breast Milk on Cholesterol Synthesis Rates in Four-Month-Old Infants. Pediatr Res 44, 60–67 (1998). https://doi.org/10.1203/00006450-199807000-00010
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199807000-00010
