Nutrient Composition for Fortified Complementary Foods
Lipid Requirements of Infants: Implications for Nutrient Composition of Fortified Complementary Foods1 Ricardo Uauy*†**2 and Carlos Castillo* *Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile; †Retina Foundation of the Southwest, Dallas, TX; and **London School of Hygiene and Tropical Medicine, London, United Kingdom ABSTRACT Dietary lipids have traditionally been considered as solely part of the exchangeable energy supply. The main consideration in infant nutrition has been the amount of fat that can be tolerated and digested by infants and young children. The significance of the composition of dietary fat has received little attention. Presently, there is a growing interest in the quality of dietary lipid supply in early childhood as a major determinant of growth, infant development and long-term health. Thus, the selection of dietary lipids during the first years of life is now considered to be critically important for health and good nutrition throughout the life course. Over the past decades interest has focused on the role of essential lipids in central nervous system development and of fatty acids and cholesterol in lipoprotein metabolism throughout life. Lipids are structural components of all tissues and are indispensable for cell and plasma membrane synthesis. The brain, retina and other neural tissues are particularly rich in long-chain PUFA. Some (n-6) and (n-3) fatty acids are precursors for eicosanoid formation; these are powerful mediators of numerous cell and tissue functions. Recommendations for infant nutrition and implications of these for the nutrient composition of complementary foods are presented and discussed. There is more to fat than its role as a key fuel in energy metabolism and body energy storage; lipids are essential for tissue growth, cardiovascular health, brain development and function throughout the life course. J. Nutr. 133: 2962S-2972S, 2003. KEY WORDS:
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infant nutrition
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complementary foods
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dietary lipids
physical activity. Lipids provide around half (45–55%) of the energy in human milk, and a similar proportion is found in most artificial infant formulas. They constitute the major energy stores in the body; the energy content of adipose tissue on a wet weight basis is seven- to eightfold higher than that of tissue containing glycogen or protein because the latter substrates are in a hydrated state. Over the past decades interest has focused on the role of essential lipids in central nervous system development and of fatty acids and cholesterol in lipoprotein metabolism throughout the life cycle. Lipids are also structural components of all tissues and are indispensable for cell and plasma membrane synthesis. The brain, retina and other neural tissues are particularly rich in long-chain PUFA (LCPUFA). Some LCPUFA derived from the (n-6) and (n-3) EFA are precursors for eicosanoid production (prostaglandins, prostacyclins, thromboxanes and leukotrienes). These autocrine and paracrine mediators are powerful regulators of numerous cell and tissue functions (e.g., thrombocyte aggregation, inflammatory reactions and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction and uterine contractility). Dietary lipids affect cholesterol metabolism at an early age and may be associated with cardiovascular morbidity and mortality in later life. Lipid supply, particularly EFA and LCPUFA, have also been shown to affect neural development and function (6 –10). Evidence indicates that specific fatty acids exert their effect by modifying the physical properties or
Lipids have traditionally been considered a part of the dietary energy supply. The total amount of fat that could be tolerated and digested by infants and young children has been the main preoccupation whereas the composition of dietary fat has received little attention. Interest in the quality of dietary lipid supply in early childhood as a major determinant of growth, infant development and long-term health is presently growing. Thus, the selection of dietary lipids during the first years of life is now considered to be of critical importance (1– 4). Fats enhance the taste and acceptability of foods, and lipid components largely determine the texture, flavor and aroma of foods. In addition they slow gastric emptying and intestinal motility, affecting satiety. Dietary lipids provide essential fatty acids (EFA)3 and facilitate the absorption of lipid-soluble vitamins (4,5). Lipids are the main energy source in the infant diet, thus necessary for normal growth and
1 Presented as part of the technical consultation “Nutrient Composition for Fortified Complementary Foods” held at the Pan American Health Organization, Washington, D.C., October 4 –5, 2001. This conference was sponsored by the Pan American Health Organization and the World Health Organization. Guest editors for the supplement publication were Chessa K. Lutter, Pan American Health Organization, Washington, D.C.; Kathryn G. Dewey, University of California, Davis; and Jorge L. Rosado, School of Natural Sciences, University of Queretaro, Mexico. 2 To whom correspondence should be addressed. E-mail:
[email protected]. 3 AA, arachidonic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EFA, essential fatty acid; FER, fat-energy ratio; LA, linoleic acid; LNA, ␣-linolenic acid; LCPUFA, long-chain polyunsaturated fatty acid; LPL, lipoprotein lipase.
0022-3166/03 $3.00 © 2003 American Society for Nutritional Sciences.
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membranes, including membrane-related transport systems, ion channels, enzymatic activity, receptor function and various signal transduction pathways. More recently the role of specific fatty acids in determining levels of gene expression for key transcription factors, peroxisome proliferator-activated receptors (PPAR) and retinoic acid receptors has renewed the interest in better defining the role of these critical nutrients in the regulation of lipid metabolism, energy partitioning, insulin sensitivity, adipocyte development and neural function across the lifespan (6 –10). Nomenclature used to characterize dietary lipids Lipids are generically defined by their limited solubility in water and by being soluble in organic solvents. Most dietary fats are triacylglycerols formed by three fatty acids esterified to a glycerol backbone. Vegetable oils, for example, consist almost entirely of triacylglycerols. The chain length of a fatty acid and the number, position and form of double bonds affect the melting point, water solubility, energy content, digestibility and metabolic properties of dietary esterified lipids. The metabolic fate, oxidative degradation, tissue deposition and effect on lipoprotein metabolism also depend on the former characteristics Fatty acids are classified by chain length as short (⬍8 carbon), medium (8 –11 carbons), intermediate (12–15 carbons) and long chain (ⱖ16 carbons). Based on their number of double bonds, they are classified as saturated, monounsaturated (1 double bond) or polyunsaturated (2 or more double bonds). The nomenclature indicates the total number of carbon atoms, number of double bonds and position of the terminal double bond. Thus stearic acid, 18:0, is a saturated carbon chain with 18 carbons and no double bonds, and oleic acid, 18:1(n-9), is a monounsaturated fatty acid with 18 carbons and 1 double bond in the (n-9) position. The position of the double bond is indicated by the carbon at which the double bond occurs; standardized nomenclature (International Union of Pure and Applied Chemistry) numbering starts from the carboxyl terminus or delta carbon; traditional or common nomenclature starts from the methyl or n- terminus (also called omega carbon). Most metabolic activity affecting fatty acids such as oxidation, desaturation and elongation affects the carboxyl end of the chain, thus changing the carbon position number relative to the delta terminus. Conversely the n- or omega terminus is rarely affected by metabolic activity and has the advantage of providing a stable base carbon position for numbering purpose. Thus, an omega-6 fatty acid, also termed (n-6) fatty acid [such as linoleic acid (LA), 18: 2(n-6)] remains a member of the (n-6) family independent of its metabolism (4,9,10). Fatty acids that are chemically identical in terms of number of carbon atoms and unsaturation may present double bonds as cis and trans isomers that have major differences in physical and biological characteristics. Animals and plants almost entirely use fatty acids with cis double bonds for metabolic and structural purposes. Cis isomers have both hydrogen atoms of the doubly bonded carbons in the same plane of symmetry, thus the molecule is bent and both acyl carbon chains may rotate using the double bond as an axis, allowing them to become more flexible and fluid. For example, the introduction of one double bond to stearic acid, 18:0, forming oleic acid, cis-18:1(n-9), takes the melting point from ⬃60°C to 16°C. On the contrary if the double bond is in the trans configuration forming elaidic acid, trans-18:1(n-9), the melting point is 56°C. Trans-isomeric fatty acids are formed naturally primarily by rumen bacteria (forestomach of grass-eating animals) and
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by chemical hydrogenation of fatty acids, which makes the fat hard and less susceptible to rancid oxidation. Trans fatty acids have a straight carbon chain with a tertiary structure similar to saturated fatty acids (10). Triacylglycerols are the main form of storage of fat in the adipose tissue. They also transport fatty acids in plasma in the form of hepatic VLDL and gut-derived chylomicrons. Phospholipids and cholesterol are indispensable components of the lipid bilayer in cell membranes, providing the interface with the aqueous environment both in plasma and in the intracellular space. The type of phospholipids, cholesterol content and fatty acid composition of phospholipids are tissue specific and to a large extent define membrane properties. Phospholipids and cholesterol play a key role in lipoprotein synthesis and metabolism. They form lipoproteins that permit the circulation of nonpolar lipids in a bipolar solvent such as plasma. Cholesterol is synthesized by all living cells because it is required for membrane renewal and formation as the cell grows or divides. Cholesterol is a necessary precursor for steroid hormone and bile acids synthesis (4). Lipid absorption and metabolism Dietary lipids are digested by the action of multiple lipases that partially or totally hydrolyze triacylglycerols into glycerol and fatty acids. Lingual and gastric lipases in the stomach primarily hydrolyze triacylglycerols in the sn-2 and sn-3 positions. In the duodenum, lipids are solubilized in mixed micelles formed by the action of conjugated bile acids, which act as emulsifiers because of their polar structure. Hydrolysis is achieved by the concerted action of intestinal lipase, pancreatic lipase, colipase, cholesterol esterase, phospholipase A2 and nonspecific lipase. Free fatty acids, monoacylglycerols and diacylglycerols are absorbed by the intestinal mucosa and later reesterified in enterocytes to form triacylglycerols, which are included with phospholipids and apoproteins, forming chylomicrons. The absorption of long-chain saturated fatty acids appears to be greater if they are esterified in the sn-2 position of the triacylglycerol molecule. Most saturated fatty acids, especially palmitic acid, 16:0, in human milk are placed in the sn-2 position of the triacylglycerol molecule. Hydrolysis will cleave the fatty acids in sn-1 and sn-3 positions, and palmitic acid from human milk will appear primarily in the remaining monoglyceride. Absorption is facilitated because palmitic acid monoglyceride is more polar and has better solubility in the hydrous phase than does free palmitic acid. Triacylglycerols from other fat sources present their saturated fatty acids esterified in random order. Thus, the main fatty acid present in human milk, palmitic acid, is better absorbed than when it is provided by other fat sources. Absorption is also greater for unsaturated than for saturated fatty acids of the equivalent chain length and is also less dependent on bile acid action. Absorption of saturated fat decreases with increasing chain length. Trans fatty acids are less absorbed than the corresponding cis fatty acids. Normal infants absorb ⬎95% of fat intake from usual sources (11–14). Long-chain fatty acids, monoacylglycerols and diacylglycerols after being absorbed are reassembled into triacylglycerols and packed together with phospholipids, cholesterol, cholesterol esters, lipid-soluble vitamins and apoproteins B48 and E to form chylomicrons. These are secreted into the lacteal lymphatic ducts, reaching the venous system via the lymphatic thoracic duct. Short- and medium-chain fatty acids are less dependent on bile acid emulsification because of their greater solubility in a water phase; after absorption they are transported directly into the portal venous system and to the liver.
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Chylomicrons lose their triacylglycerol content as they progress through the circulation. They are hydrolyzed by lipoprotein lipase (LPL) present in the vascular endothelial cells, and free fatty acids are taken up in the periphery by muscle and adipose tissue. The quality of the fat consumed modulates the activity of LPL and the clearance of chylomicrons. Unsaturated fatty acids result in chylomicrons of larger particle size that are cleared more effectively by LPL because of its greater affinity for unsaturated fatty acids. Diets rich in (n-6) and (n-3) LCPUFA can significantly reduce postprandial lipemia. Leftover particles (chylomicron remnants) are taken up primarily by the liver by LDL receptors and chylomicron remnant receptors. The liver secretes triacylglycerol-rich VLDL containing apoproteins B 100 and E, which serve as the transport system to the periphery. VLDL is also subject to the action of LPL, which liberates free fatty acids for tissue energy metabolism or adipose tissue storage. Triacylglycerol synthesis in the liver depends primarily on the balance between fatty acid uptake and oxidation; there is very limited de novo fatty acid synthesis. Saturated fatty acids increase plasma VLDL whereas they are reduced by unsaturated fatty acids and particularly by (n-3) LCPUFA, as present in fish oil. These fatty acids enhance the rate of lipolysis and also decrease hepatic VLDL synthesis. As VLDL loses it triacylglycerol content, it forms intermediate-density lipoproteins, which can be taken up by the liver or depleted further in triacylglycerol content while increasing its cholesterol content, forming LDL. The formation and removal of LDL by hepatic receptors are also affected by type of fat consumed. LDL is taken up primarily by the liver (70%); the rest is taken up by other organs and peripheral tissue. Dietary saturated fatty acids, especially C12, C14 and C16 (lauric, myristic and palmitic acids, respectively) suppress LDL receptor activity and LDL removal whereas unsaturated fatty acids, especially LA, enhance receptor activity. LDL may be modified by peroxidation, enhanced by PUFA and proxidants (e.g., iron or copper) and inhibited by antioxidants (e.g., ascorbic acid and ␣-tocopherol). Modified LDL is rapidly removed from the plasma by macrophages and scavenger cells present in all tissues, including vessel walls. Vascular lipid deposition is enhanced by a high plasma concentration of LDL and reduced by a high plasma concentration of HDL. Disc-shaped nascent HDL formed by the liver and to a certain degree by all tissues contains apoprotein AI and AII. They contain low amounts of triacylglycerol and high amounts of phospholipid and thus are dense. Cholesterol from peripheral tissues, including vessel walls, is taken up by HDL. High HDL concentrations protect against vascular cholesterol deposition and the development of atherosclerosis (15–21). Metabolism of EFA Animal tissues, especially the liver, can further elongate and desaturate the parent EFA, generating a family of compounds for the respective families as shown in Figure 1. As depicted in the figure, arachidonic acid [(AA) 20:4(n-6)] can be formed from LA; it becomes essential only if the capacity for elongation and desaturation of LA is limited, which occurs in the cat and other felines. Further details on EFA metabolism can be found in referenced reviews (2,8,9,22). The competitive desaturation of the (n-3), (n-6) and (n-9) series by delta-6 desaturase is of major significance because this is the controlling step of the pathway (23,24). Sprecher’s group (22) proposed that the last reaction apparently catalyzed by delta-4 desaturation is a three-step path as depicted in
FIGURE 1 Metabolic transformation of essential fatty acids (EFA) to form long-chain PUFA (LCPUFA). Parent EFA are derived from dietary sources for both (n-3) (18:3, ␣-linolenic acid) and (n-6) series (18:2, linoleic acid). De novo synthesis is able to produce only (n-9) LCPUFA. Elongation occurs 2 carbons at a time and delta desaturases (⌬-9, ⌬-6, ⌬-5) introduce double bonds at 9, 6 and 5 carbons from the carboxylic moiety. The final step in the formation of (n-3) and (n-6) end-products is catalyzed by a peroxisomal partial beta-oxidation. PUFA of interest include 18:3(n-6) gamma linolenic acid, arachidonic acid 20:4(n-6) (AA), docosapentaenoic acid 22:5(n-6), eicosatrienoic acid 20:3(n-9), EPA 20:5(n-3) (EPA) and DHA 22:6(n-3). EPA, AA and 20:3(n-6) are immediate precursors of prostaglandins and other eicosanoids.
Figure 1. The initial step is an elongation, which is followed by delta-6 desaturation and then, through a peroxisomal betaoxidation, the chain is shortened to a 22-carbon PUFA. This latter step has been termed a retroconversion (22). The Sprecher pathway has been verified for both docosahexaenoic acid [(DHA), 22:6(n-3)] and docosapentaenoic acid [(DPA), 22: 5(n-6)] formation. The delta-6 desaturase in the Sprecher pathway is likely different from the enzyme responsible for the initial step of the parent EFA metabolism. If (n-3) fatty acids are absent or deficient in the diet, the elongation and desaturation of the (n-6) compounds generates a significant elevation of DPA; if both EFA are lacking, eicosatrienoic acid, 20:3(n-9), accumulates. The ratio of trienes to tetraenes may be used as an index of EFA deficiency but is not valid as a marker of isolated (n-3) deficit (4,9,10). Lipids in infant nutrition Human milk is the preferred mode of infant feeding. Nutrition recommendations suggest that term infants be exclusively breast-fed for the first 6 mo of life. Present approaches to evaluating the adequacy of formula feeding are based on the capacity of formula to support growth and development in a
LIPID REQUIREMENTS OF INFANTS
manner comparable with human milk. This includes the need to compare the biochemical, metabolic and functional responses of breast-fed infants to those given defined formula diets. Human milk provides a fat-energy ratio (FER) of 50%. Most of the fat is provided as saturated and monounsaturated fatty acids and a relatively high cholesterol intake of 100 –150 mg/d. Formula-fed infants receive a similar FER but in contrast receive a much lower cholesterol intake, 25– 60 mg/d. A mix of vegetable oils (corn, soy, safflower, olive or sunflower) is added to most formulas. The oleic acid or LA content will depend on the oil source. The use of vegetable oils in the infant diet is based on availability, nutritional properties and relative costs. The need to include LA, the parent (n-6) EFA, has been recognized for over 40 y. More recently the need to provide ␣-linolenic acid [(LNA), 18:3(n-3)] as a source of the (n-3) EFA found in retinal and nervous system development has been recognized. A possible need for long-chain fatty acids (⬎18-carbon chain length) derived from EFA has recently been established. The (n-6) PUFA are abundant in commonly used vegetable oils whereas (n-3) PUFA are relatively low except in soy, canola and linseed oils (Table 1). Presently, most formulas are designed to provide a similar fatty acid composition to that found in mature human milk from omnivorous women. This precision is necessary, because the fatty acid composition of human milk will vary based on the maternal diet. The EFA content of human milk, especially the LCPUFA content, will change according to the maternal diet. Cholesterol has not been routinely added to formula except in experimental products used in clinical research. The beneficial effects of cholesterol supplementation of artificial formula have not been established (10,25–28). EFA needs for growth and development George and Mildred Burr in 1929 (29) introduced the concept that specific components of fat may be necessary for the proper growth and development of animals and possibly humans. The Burrs proposed that three fatty acids be considered essential: LA, AA and LNA. The essentiality of (n-6) and (n-3) fatty acids for humans is best explained by the inability of animal tissues to introduce double bonds in positions before carbon 9, counting from the methyl terminus. EFA were considered of marginal nutritional importance for humans until the 1960s, when signs of clinical deficiency became apparent in infants fed skim milk– based formula and in those given lipid-free parenteral nutrition (30).
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Hansen et al. (31) firmly established that LA is essential for normal infant nutrition in a clinical and biochemical study of 428 infants fed cow’s milk– based formulations with different types of fat. Daily LA intake of study infants ranged from 10 mg/kg when a fully skim milk– based preparation was fed to 800 mg/kg when a corn and coconut oil– based preparation was fed. Hansen et al. observed dryness, desquamation and thickening of the skin and growth faltering as frequent manifestations of LA deficiency in young infants. More subtle clinical symptoms appear in (n-3) EFA deficiency. They include skin changes unresponsive to LA supplementation, abnormal visual function and peripheral neuropathy. The nervous system manifestations of (n-3) deficit are likely caused by an insufficiency of the specific metabolic derivative of LNA, namely DHA. Indeed, the high concentrations of DHA in cerebral cortex and retina support its role in neural and visual function (32). Studies of several animal species and recent evidence from humans have established that brain phospholipid AA and DHA decrease whereas (n-9) and (n-7) monopolyunsaturated and PUFA increase when LA and LNA or only (n-3) fatty acids are deficient in the diet. Typically, cells deficient in (n-3) fatty acids have decreased DHA and increased levels of the end product of (n-6) metabolism, DPA. Within the subcellular organelles, synaptosomes and mitochondria seem to be more sensitive to a low dietary (n-3) supply as evidenced by the relative abundance of DHA and the changes in composition of these organelles in response to dietary deprivation (33). The evidence indicates that in early life 18(n-3) precursors are not sufficiently converted to DHA to allow for biochemical and functional normalcy (23,24). Thus, not only LA and LNA but DHA and AA are now considered necessary nutrients for normal eye and brain development in the human. The role of LCPUFA derived from EFA in prevention of disease mediated by eicosanoid is also being increasingly recognized (34,35). The LCPUFA AA, eicosapentaenoic acid [(EPA) 20:5(n-3)] and DHA are important membrane components and precursors of potent bioactive oxygenated products. Eicosanoids such as prostaglandins, leukotrienes and epoxides derived from AA and EPA are required in numerous physiologic processes. Blood pressure, vascular reactivity, inflammation, platelet aggregation, immune function, allergy and cytokine release are all modulated by dietary AA and EPA intake (Fig. 2.) A myriad of clinical correlates associated with LCPUFA intake have been observed (34,36). The conversion of parent EFA to LCPUFA is under active regulation, therefore, the effects of providing AA, EPA or DHA cannot be reproduced by providing the equivalent
TABLE 1 Composition of commonly used vegetable oils Source of oil
Fat
Saturates
Monounsaturates
Polyunsaturates
(n-6) PUFA
(n-3) PUFA
g Canola Corn Sunflower Rapeseed Soya Olive Vegetable solid fat Animal fat lard Milk fat
100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 81.1
Cholesterol mg
7.10 12.70 10.30 6.80 14.90 13.50 25.00 39.20 50.49
58.90 24.20 19.20 55.50 43.00 73.70 44.50 45.10 23.43
29.60 58.70 65.70 33.30 37.60 8.40 26.10 11.20 3.01
20.30 58.00 65.70 22.10 34.90 7.90 2.50 10.20 1.83
9.30 0.00 0.00 11.10 2.60 0.60 1.60 1.00 1.18
0 0 0 0 0 0 0 95 219
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FIGURE 2 Schematic representation of the role of (n-6)/(n-3) fatty acid balance in determining membrane phospholipid composition and eicosanoid production. Excess (n-6) favors arachidonic acid– derived series 2 eicosanoids whereas EPA generates series 3 eicosanoids that antagonize the former.
amount of LA or LNA. The uniqueness of the biological effects of feeding human milk on EFA metabolism is based on the direct supply of LCPUFA, bypassing the regulatory step of the delta-6 desaturase (23,24). Excess dietary LA associated with some vegetable oils, particularly safflower, sunflower and corn oils, may decrease the formation of DHA from LNA because the delta-6 desaturase is inhibited by excess substrate. In addition AA formation is lower when excess LA is provided. The inhibitory effect of EPA on delta-5 desaturase activity has been considered responsible for the lower AA observed when marine oil is consumed. Excess LA, as seen in infants receiving corn oil or safflower oil as the predominant FA supply, will inhibit the elongation and desaturation of the parent EFA and thus lower the LCPUFA supply necessary for membrane synthesis. Human milk and LCPUFA from dietary sources provide minimal preformed AA and substantial amounts of preformed (n-3) LCPUFA such as DHA (23,37– 40). Lipids as an energy source for growth and development Dietary triacylglycerols have the highest chemical energy value of all fuel sources, ⬃9 kcal/g compared with 4 kcal/g for carbohydrates and protein. Fat contributes ⬃35% of the energy required and ⬃90% of the energy retained during the first 6 mo of life in a healthy infant. Infants can form saturated and monounsaturated lipids de novo for tissue deposition but the capacity for endogenous synthesis is limited. Endogenous lipid synthesis is an energy-demanding process. The synthesis of fat from glucose requires ⬃25% of the energy from glucose for the cost of fat synthesis whereas the storage of fat from preformed fatty acids requires only ⬃1– 4% of the energy in the fat. The isoenergetic supply of fat relative to carbohydrate leads to a greater weight and fat gain and a lower energy expenditure in infants. Medium-chain triacylglycerols provide less energy than do long-chain triacylglycerols. Medium-chain triacylglycerols contain 8 –10 carbon atoms and are easily absorbed and thus serve to treat fat malabsorption. However, because of their shorter chain length, their energy content is only 7.5– 8.0 kcal/g fat. Medium-chain triacylglycerols are very rapidly oxidized and have a higher thermogenic effect; they enter the mitochondria and are metabolized directly by a carnitine independent system. Fat increases the palatability and caloric density of the diet and usually enhances total energy intake. Obese children who consume high fat diets tend to have a greater weight gain whereas infants who consume low fat diets
(fat content ⬍ 25% of total energy intake) commonly fail to thrive (4,41,42). The energy cost of growth is an important component (20 –30%) of total energy requirements for the first 6 mo of life, progressively dropping its significance to ⬍5% at age12 mo. Weight gain is a sensitive indicator of overall dietary adequacy for the first years of life. If the diet supplies adequate energy and essential nutrients, there is no convincing evidence that a dietary fat intake of 30% of energy adversely affects the growth and development of healthy children living in a clean environment. A review of studies from Europe and North America found little evidence of adverse effects of low dietary fat on growth of young children 6 –36 mo of age (43– 49). Percentage of dietary fat was not correlated with energy intake, growth velocity or energy density of the diet between ages 6 and 12 mo whereas energy density was positively associated with energy intake and weight gain. Dietary energy density, nutrient density and feeding frequency may be more important than dietary fat content in determining intake and growth of young children. No association between fat intake and growth was detected in infants aged 7–13 mo, children aged 2–5 y or children aged 3–5 y (50 –52). In the STRIP trial, moderately restricted fat intake (25– 30% of energy) was not associated with compromised infant growth between 7 and 36 mo (53). A similar intervention with a fat intake of 30 –35% in French infants aged 7 mo also did not result in impaired growth between ages 7 and 13 mo (54). A number of studies found lower energy intakes with low fat diets but no differences in growth. If the diet records accurately reflect habitual intake, these findings raise the possibility of decreased physical activity in infants and young toddlers adapted to low fat diets. Several studies on secular trends, migration and vegetarian diets link dietary fat restriction to slower growth. Unfortunately, these studies are confounded by inadequacies in total energy and micronutrient intake (55). Some investigators have reported lower vitamin and mineral intakes in association with low fat diets (56,57). A cohort of 500 Canadian preschoolers was stratified according to fat intake: ⬍30%, 30 – 40% or ⬎40% of energy from fat between ages 3 and 6 y. Low fat intake was associated with inadequate intake of fat-soluble vitamins. For children habitually on low fat diets, the odds ratio for underweight for age at age 6 y was 2.3 (58). The relationship between dietary fat intake and body fat in children has been examined in a number of studies. Unfortunately, the commonly used measurement of skinfold thickness is not the most sensitive predictor of body fat. The effect of dietary fat on growth of 140 children in New Zealand was examined at ages 2, 4, 6 and 8 y (59). Median percent dietary fat intake fell from 44% at 3 mo to 36% at 6 mo and remained at a similar level until 8 y. At each age interval no differences in height, weight or skinfold thickness were observed among children consuming ⬍30%, 30 –34.9% and ⬎34.9% of dietary energy as fat. Maffeis et al. (60) recorded a diet history and measured the skinfold thickness of 82 prepubertal Italian children. Mean fat intake was 36.6% in obese children and 33.8% in nonobese children. Percent dietary fat was weakly correlated with body fat mass (%). Gazzaniga and Burns (61) studied 48 lean and obese American children and reported that the obese children consumed higher proportions of total energy as fat. Percent fat mass was positively correlated with dietary fat intake independent of total energy intake. Fisher and Birch (62) found that children who preferred high-fat snacks consumed a high percentage of total energy as fat and had high triceps skinfold measurements. Ricketts (63) obtained diet records, preference ratings of high and low fat
LIPID REQUIREMENTS OF INFANTS
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TABLE 2 Fat content of some common complementary foods consumed by African children1 Food name
First weaning foods Rice gruel plus sugar Millet gruel plus sugar Rice gruel plus sour milk Rice porridge Rice and groundnut porridge Family foods Staples Rice, boiled Millet, steamed Sauces Groundnut sauce Leaf sauce plus groundnuts Sour leaf sauce Flour and tomato sauce Oil sauce Meals Rice plus groundnut sauce Rice and groundnuts, steamed Rice ⫹ leaf & groundnut sauce Rice ⫹ sour leaf sauce Rice plus oil & vegetable sauce Groundnuts
Local name
Energy
Energy
kcal/100 g
kJ/100 g
40 50 50 54 68
167 209 209 226 285
87 85 85 83 83
Mani fajiringo Sanyo nyelengo
114 152
477 636
Tia durango Jambo, plus tio Kucha/Domoda Bukolo Sauso tulo
92 107 34 42 294
Mani Mani Mani Mani Mani Tio
108 153 102 88 186 571
Mani mono plus sukuro Sanyo mono plus sukuro Mani mono plus ninsi nono Mani churo Tiakere churo
fajiringo plus tia durango nyankantango fajiringo plus jambo fajiringo plus kucha fajiringo plus sauso tulo
Water
Fat
Fat
Fat
g/100 kcal
% Energy
0.1 0.2 1.2 0.3 1.9
0.3 0.4 2.4 0.6 2.8
2.3 3.6 21.60 5.0 25.10
66 58
0.5 0.6
0.4 0.4
3.9 3.6
385 448 142 176 1230
80 78 87 88 64
6.6 7.3 0.4 0.4 30.30
7.2 6.8 1.2 1.0 10.30
64.60 61.40 10.60 8.6 92.80
452 640 427 368 778 2365
71 63 70 73 62 4
2.2 4.5 2.2 0.5 6.5 49
2.0 2.9 2.2 0.6 3.5 8.6
18.30 26.50 19.40 5.1 31.50 77.20
g/100 g
1 Based on Hudson et al. (65).
snack foods and skinfold measurements on 88 American children, aged 9 –12 y. Mean percent dietary fat was 34%. Children who preferred the high fat snacks had high dietary fat intakes. High fat food preference was associated with higher body mass index and triceps skinfold measurements. These studies suggest that children establish food preferences at an early age. In summary, data from industrialized countries suggest that if diet supplies adequate energy and essential nutrients, a dietary fat intake of 30% of energy is adequate for normal growth and development of healthy children. Prentice and Paul (64) described the total fat intake of the Gambian infants over their first 17 mo, showing relatively little change in intake on an absolute basis and therefore a marked decline per kilogram of body weight. Fat intake was highest in the first 3 mo and was provided almost entirely by human milk; as infancy progressed, an increased intake of cereal- and groundnut-based foods containing little fat replaced the gradual decline in human milk (Table 2). The percent energy from fat was initially ⬎50% and declined to 30% by 17 mo. Once infants were fully weaned at around 2 y, both fat intake and fat percent energy fell very substantially, the latter being only 15%. Dietary fat was provided chiefly by groundnuts, but cereals were also important because relatively large quantities were eaten (Fig. 3). The few fat-rich foods were those containing oil, but these expensive items were not frequently used. Data on total fat intake including specific fatty acid intake of Gambian compared with British children are provided in Table 3. LCPUFA intakes expressed per unit of boy weight drop significantly in Gambian children after 12 mo. Higher total energy and saturated fat intake of British children is clearly evident from these results. Given the very limited data from developing countries, we evaluated the effect of diet-related variables obtained from national food balances on growth indexes of children under age 6 y across 18 countries in Latin America (5). A simple
correlation analysis using a linear model was tested. Underweight prevalence was negatively related to available energy and FER but the strongest correlation was with animal fat as percentage of total fat (r ⫽ ⫺0.66). For the 12 countries with the lowest animal fat intake, the correlation was r ⫽ ⫺0.83 (P ⬍ 0.001) whereas for countries with ⬎45% of total fat from animal sources, the correlation was r ⫽ ⫺0.1 (not significant). Stunting was negatively related to energy (r ⫽ ⫺0.53), FER (r ⫽ ⫺0.45) and percent animal fat (r ⫽ ⫺0.54). For countries with FER ⬍ 0.22, the correlation with stunting was stronger (r ⫽ ⫺0.6, P ⬍ 0.05) whereas for those with FER ⬎ 0.22, there was no correlation (r ⫽ ⫺0.01). Weight for length of children
FIGURE 3 EFA intake, precursors linoleic acid 18:2(n-6) and ␣-linolenic acid 18:3(n-3) and long-chain products arachidonic acid 20:4(n-6), DHA 22:6(n-3) observed in The Gambia during the first 3 y of life. Modified from Prentice and Paul (64).
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TABLE 3 Fatty acid intakes of Gambian and British infants1 Gambian
Number Body weight, kg Total energy, kcal/d Total energy, MJ/d Total fat, g/d Total saturates, g/d Total monounsaturates, g/d Total polyunsaturates, g/d p/s ratio 18:2(n-6), g/d 20:4(n-6), g/d 18:3(n-3), g/d 22:6(n-3), g/d Total (n-6), g/d Total (n-3), g/d (n-6): (n-3) 18:2, % energy 18:3, % energy 18:2, mg/kg body weight 18:3, mg/kg body weight 20:4 n-6 mg/kg body weight 22:6 n-3 mg/kg body weight
British
0–6 mo
7–12 mo
13–17 mo
24 mo
147 5.18 552 2.31 28.35 10.00 13.74 4.61 0.46 3.69 0.09 0.23 0.11 4.16 0.45 9.2 6.00 0.38 710 44 17 21
119 7.30 709 3.30 27.09 9.11 12.98 5.00 0.55 4.23 0.07 0.22 0.09 4.61 0.41 11.40 5.40 0.28 580 30 10 12
115 8.39 878 3.68 26.85 8.49 12.75 5.61 0.66 4.95 0.06 0.22 0.08 5.26 0.38 13.70 5.10 0.23 590 26 7 9
42 9.90 780 3.27 13.00 3.16 5.86 4.09 1.29 3.99 0.01 0.12 0.01 4.00 0.14 29.40 4.60 0.13 403 12 1 1
6–12 mo 488 868 3.65 35.60 17.60 10.80 3.5 0.20
18–30 mo 576 12.25 1045 4.39 42.50 19.70 13.00 5.1 0.26
4.3 0.8 5.4
1 Modified from references 64, 66, and 67.
was not related to dietary factors, suggesting that the small percentage of children who are wasted are in that condition secondary to bad sanitation, infections or particular dietary factors that do not affect most of the community. Prevalence of low birth weight was negatively related to energy (r ⫽ ⫺0.64), percent animal fat (r ⫽ ⫺0.63) and energy from animal fat (r ⫽ ⫺0.65). Despite the limitations of national food balances as putative indices of food intake and of national aggregated growth data, these results suggest that diets that provide ⬍22% of energy from fat and are low in animal fats (⬍45% of total fat) restrict infant growth as evidenced by strong correlation with prevalence of underweight and stunted children. Multivariate analysis of these data sets included the availability of specific food groups (dairy, meats and oils). The main food determinants of underweight were availability of dairy, oils and meats (multiple R ⫽ 0.81, R2 ⫽ 0.66; P ⬍ 0.0008). The main factors linked to stunting were protein, total fat, total energy and animal fat (multiple R ⫽ 0.58, R2 ⫽ 0.34, P ⬍ 0.09). The main conclusion from this analysis is that animal flesh food products are important to support normal growth of children. They provide good quality protein, essential fats and micronutrients key for normal growth and development. The coexistence of early stunting with the progressive increase in urban obesity in Latin America creates a dilemma for complementary feedings programs. The need to improve growth beyond providing increased energy supply is suggested by the analysis. The association of improved growth with animal fat and protein suggests that micronutrients (e.g., vitamin A, zinc and iron) or other essential components [essential amino acids or (n-6) and (n-3) fatty acids] may be limiting the growth of Latin American children. Cholesterol in the infant diet Interest in the effect of high cholesterol feeding in early life arose after Reiser et al. (28) proposed that high cholesterol
feeding in early life may regulate cholesterol and lipoprotein metabolism in later life. Animal data in support of this hypothesis are limited but the idea of a possible metabolic imprinting triggered several retrospective and prospective studies comparing cholesterol and lipoprotein metabolism in human milk–fed and formula-fed infants. Studies in suckling rats have suggested that the presence of cholesterol in the early diet may define a metabolic pattern for lipoproteins and plasma cholesterol that could be of benefit later in life, a hypothesis attributed to the work of Reiser et al. (28). Differential diets in infant baboons studied by Mott et al. (68) provided evidence to the contrary in terms of benefit. Nevertheless, the observation of modified responses of adult cholesterol production rates, bile cholesterol saturation indexes and bile acid turnover depending on whether the baboons were fed human milk or formula attracted further interest. They noted that increased atherosclerotic lesions associated with increased levels of plasma total cholesterol were related to increased dietary cholesterol in early life. However, no long-term human morbidity and mortality data supporting this notion have been reported. Short-term human studies have been in part confounded by diversity in solid food weaning regimens as well as varied composition of fatty acid components of the early diet; the latter are now known to affect circulating lipoprotein cholesterol species (69). Mean plasma total cholesterol by age 4 mo in human milk–fed infants reached ⱖ4.65 mmol/L whereas cholesterol values in formula-fed infants tended to remain ⬍1.29 mmol/L. In a study by Carlson et al. (70), infants receiving predominantly an LA-enriched oil blend exhibited a mean cholesterol concentration of ⬃2.84 mmol/L. A separate group of infants in that study receiving predominantly oleic acid had a mean cholesterol concentration of 3.44 mmol/L; moreover, infants fed human milk and oleic acid– enriched formula had relatively higher HDL cholesterol and apoproteins A-I and A-II than did the infants fed predominantly LA-enriched formula. The ratio of LDL⫹VLDL cholesterol to
LIPID REQUIREMENTS OF INFANTS
HDL cholesterol was lowest for infants receiving the oleic acid–predominant formula. Using a similar oleic acid–predominant formula, Darmady et al. (71) reported a mean value of 3.85 mmol/L at age 4 mo compared with 5.07 mmol/L in a parallel breast-fed group. Most of those infants then received an uncontrolled mixed diet and cow’s milk, with no evident differences in plasma cholesterol levels by 12 mo that were dependent of the type of early feeding they had received. We (72) assessed the effect of feeding a controlled lipid diet on plasma cholesterol lipoprotein fractions. We used a prospective randomized diet-controlled study in matched populations of Caucasian normal growing infants from birth to age 12 mo followed by free access to food from age 12 to 24 mo. The experimental approach was based on the comparison of oleic acid– and LA-predominant diets (both low in cholesterol) compared with human milk (oleic acid predominant and high in cholesterol). Study subjects were enrolled from a population of 68 healthy infants from highly motivated families followed in a single private practice office in North Dallas. The two formulas provided each infant 15–25 mg cholesterol/d depending on intake volume. After being weaned, the two formula groups received a selection of predefined solid foods and oil supplementation, provided by the investigators, to maintain a daily fatty acid intake resembling that of the initially assigned infant formula but with a lower total fat content (35% of total energy). As solid foods were introduced, the decrease in fat energy from the formula-only feeding was adjusted to preserve the relative fatty acid composition by using either oleic acid– enriched (High-Oleic group) or LA-enriched (High-Linoleic group) oil supplements (California Fats & Oils, Richmond, CA). For the remainder of the study, the selected foods together with either oleic acid– or LA-rich safflower oil supplements provided a daily intake of individual fatty acids that paralleled the assigned preweaning diets. A third group, fed human milk, was weaned at a mean age of 6.2 mo (range 4 – 8.5 mo) and after weaning until age 12 mo received a mixed diet resembling human milk in its cholesterol (150 –200 mg/d, i.e., ⬃1 egg yolk equivalent) and oleic acid content. This was accomplished by using added egg yolk and the same formula as for the High-Oleic group. The selected solid foods and oil supplements given to all infants after weaning were designed to maintain the fatty acid and cholesterol intake of the assigned diet group. Postweaning, all infants received, as a function of increasing age, 110 –120 kcal/(kg 䡠 d) and 2.5–3.0 g protein/(kg 䡠 d), which was customary for this population. The diets provided vitamins and minerals to meet or exceed the Recommended Dietary Allowances according to age. As a result of weaning, the percentage of energy delivered as fat decreased in all groups from 50% (to age 4 mo) to 35% (from ages 4 to 12 mo). Our study showed significant effects of exclusive human milk feeding on lipoprotein-cholesterol concentrations at age 4 mo. At ages 9 and 12 mo, while maintaining cholesterol and fatty acid intakes to mimic human milk, this group had concentrations that were not different from those of the High-Oleic formula group (low cholesterol). The High-Linoleic formula group (also low cholesterol) had lower total and LDL cholesterol throughout the study. Thus our data suggest that the specific fatty acid intake plays a predominant role in determining total and LDL cholesterol. We cannot discard a role for high dietary cholesterol associated with exclusive human milk feeding during the first 4 mo of life, because at this time the human milk–fed group had significantly higher total and LDL cholesterol than did the High-Oleic group. In summary, measurements of serum lipoprotein concentra-
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tions and LDL receptor activity in infants suggest that it is the fatty acid content rather than the cholesterol in the diet that regulates cholesterol homeostasis. The regulation of endogenous cholesterol synthesis in infants appears to be regulated similarly to that of adult humans (73,74). Safety concerns for edible fats used in complementary feeding products Because the quality of the fat supply is of special relevance to developing countries, selection of fat sources for infant complementary foods must consider more than fat absorption. In many developing countries, fats included in foods given to young children are low cost oils or solid fats that are byproducts of industrial processing. For example, fish oil produced as a by-product of fish meal processing has been hydrogenated and included in complementary foods in Peru and Chile. Evaluation of absorption revealed that if 100% hydrogenated marine oil was fed to children recovering from malnutrition, fecal fat loss was 20%; when this source was mixed in a 1:3 proportion with vegetable oils, fat loss was reduced to ⬃5%. (Carlos Castillo, unpublished data, 1984). The trans fatty acid content of hydrogenated fish oil was extremely high, on the order of 30%, raising serious concerns about long-term safety given the effects of trans acids on lipoprotein metabolism. Diets high in trans fatty acids increase LDL cholesterol, reduce HDL cholesterol and possibly increase lipoprotein(a). All of these changes increase atherogenicity. Trans fatty acids formed during hydrogenation have other problems. They are not substrates for LCPUFA formation and thus increase the need for EFA. For example if all-cis-18: 2(n-6) is replaced by cis-trans-18:2(n-6), it does not work as an EFA. The impairment of LCPUFA synthesis by trans fatty acids should be considered in view of the importance of LCPUFA availability for infant growth and development. Furthermore, a reduction of postnatal growth was observed in animals exposed to high levels of trans fatty acids. The extent of EFA deficiency in developing countries is virtually unknown, especially because the clinical manifestations occur only in extreme deficiency. Thus, this problem may go unreported despite the potential effects in central nervous system development. Improvement of the quality of the energy supply of infants in developing countries is urgently needed to avoid inducing problems in later life. Low price and shelf-life stability of hydrogenated fats has been the reason for their inclusion in complementary foods and other products given to children. However, this needs to be balanced against the possible longterm adverse effects of this type of fat. The European Union set an upper limit of 4% of total fat for the trans fatty acid content of foods for infants and young children. Children of low socioeconomic status should be given food products that meet long-term safety standards and are not just the cheapest source of energy available. The issue of chemical composition is as relevant for lipid sources as it is to protein. Fats are structural components of tissues, especially neural tissues; (n-3) and (n-6) fatty acids are essential and must be provided by the diet. In most developing countries, fats included in foods, even those given to young children, are by-products of one of many industrial processes. For example, consider coconut oil, partially or fully hydrogenated fish oil and hydrogenated vegetable fats of low cost such as cotton oil. Coconut oil has a high content of saturated fatty acids with intermediate chain length (lauric acid and myristic acid); these fatty acids are well absorbed but contribute to raising LDL cholesterol. Human milk has relatively low con-
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centrations of lauric (⬃5–7%) and myristic acids (⬃6 – 8%). Some countries have placed limits on dietary intakes of lauric and myristic acids to prevent adverse long-term effects (64). Another safety issue in fats and oils used for complementary feeding in developing countries is the need to avoid the use of rapeseed oil with high concentrations of erucic acid. Erucic acid is a long-chain monounsaturated fatty acid [trans-22:1(n9)] found in high amounts in some types of rapeseed oil. Absorbed erucic acid is oxidized slowly and accumulates in myocardium, causing myocardial lipidosis and functional abnormalities in myocardial mitochondria. These side effects are observed at high but not at low (⬍1% of dietary fatty acids) levels of intake. Canada has developed low erucic acid rapeseed oil seeds under the registered trade name “canola” (75,76). If this is not monitored, toxicity from erucic acid may occur, again virtually impossible to diagnose clinically. If rapeseed oil is to be used it should be derived from genetically low erucic acid varieties. Unfortunately these oil seeds revert to erucic acid–producing phenotypes with an increasing content of this fatty acid. Thus, certified low erucic acid seeds should be purchased every year. These seeds may be costly and farmers in developing countries may not use them unless forced by appropriate quality control measures. Other components of vegetable oils may have adverse effects for infants and young children. Unsaponifiable ingredients in sesame seed oil have been reported to cause allergic reactions, and cyclopropenoids in cotton seed oil impair EFA desaturation. Therefore, the use of both oils in the production of infant foods has been prohibited in Europe. Another critical safety issue is the stability of oils in terms of lipid peroxidation, noticed as rancidity by smell and taste. Highly unsaturated oils such as fish oil or vegetable oils used in human foods or as animal feed require substantial amounts of synthetic antioxidants to preserve their structure and prevent rancidity. Most legislation authorizes the use of up to 0.1% butylated hydroxytoluene, butylated hydroxyanisole, tert-butylhydroquinone and propyl or octyl gallate as total antioxidant. This is in accordance with Codex, despite some existing concerns with the safety of synthetic antioxidants, which have led some countries to restrict their use (77). A specific issue in the use of processed fish oil for animal feed is the safety concern of ethoxyquine or its mixtures used as an antioxidant in the product. Ethoxyquine is a highly efficient antioxidant and anticombustion agent but is prohibited in human food products. The consumption of poultry or other animals fed fish
meal or fish oil containing ethoxyquine is a safety issue that has not been addressed by present regulatory efforts. Research is underway to find alternative antioxidants to replace ethoxyquine at reasonable prices. Safety problems may be associated with how oils are dispensed. Large tin or plastic barrels used in developing countries to reduce costs may facilitate adulteration of products and promote peroxidation given the large volume and the long time until the total product is sold. A recent study in marasmic children demonstrated altered antioxidant defense systems and increased lipid peroxidation, suggesting an increased risk of oxidative damage in malnourished infants (78). Bottled oil ready for consumer purchase is undoubtedly safer but is also more expensive. Soft plastic containers made with phthalic acid as plasticizer can also create safety problems because this agent is fat soluble and a known carcinogen; rigid plastics or glass bottles are preferable (79). Tetrapak brick containers have recently been introduced in some countries in the Americas. This container prevents rancidity because exposure to light and oxygen are prevented by the metallic component of the packaging material and the nitrogen used to displace air in the container. Recommendations and conclusions The following recommendations are based on existing national and international reports (10,57,80 – 83): ● During the first 4 – 6 mo of life, dietary total fat should contribute 40 – 60% of total energy to cover the energy needed for growth and the fat required for tissue deposition. From age 6 mo to 3 y, fat intake should be reduced gradually, depending on the physical activity of the child, to ⬃30 –35% of energy (Table 4). ● Health promotion efforts for the general population emphasize the importance of limiting the dietary intake of saturated and total fats to prevent nutrition-related chronic disease (cardiovascular disease, obesity, type 2 diabetes and some types of cancer). This has lead to a reduction of total lipid intakes in children of some populations, reaching average values as low as 28 –30% energy after age 6 –12 mo. Adverse effects of low fat diets (⬍25% of energy) on weight gain and longitudinal growth in young children has been documented. Lowering saturated fat but not total fat intake may be considered exclusively in children from families with evidence
TABLE 4 Recommendations on the dietary intake of total fat (% of energy intake) for infants and young children according to different consultative bodies Age range 0–4 (–6) mo
6–12 mo
12–24 mo
24–36 mo
% American Academy of Pediatrics Committee on Nutrition, 1986 (80) American Academy of Pediatrics 1992 (81) Canadian Society of Pediatrics, 1993 (50)1 European Union 1996 (82) European Society for Pediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition 1991 & 1994 (21, 83) World Health Organization/Food & Agriculture Organization ’94 (10) 1 No restriction of fat intake in children. 2 Recommendation for follow-on formulas only, not for total diet.
— — — ⱖ40–58.5%
— — — ⱖ32–58.5%2
— — — —
30–40% 30%
ⱖ40–58.5% 50–60%
ⱖ32–58.5%2
No restriction 30–40%
30–35% 30–40%
—
LIPID REQUIREMENTS OF INFANTS
of dyslipidemia due to high LDL cholesterol or elevated triglyceride levels. ● The total diet should provide infants with at least 3– 4.5% of total energy from LA and at least 0.5% energy from LNA to meet EFA requirements. Very high intakes of EFA have no advantage and are associated with potential health risks. Intake of LA and other (n-6) fatty acids should be limited to ⬍10% of energy and intake of total PUFA should be limited to ⬍15% energy. After age 2 y the composition of dietary fat should be aimed at reducing the risk of diet-related chronic diseases (Table 5). Saturated fatty acid intake should not exceed 10% total energy and trans fatty acids should be avoided. PUFA should contribute ⬃6 –10% of energy and the remaining fat energy should come from monounsaturated fatty acids. There is no need to limit or restrict fat intake in active healthy children with normal body weight. One practical approach to limiting saturated fat is to advise consumption of low fat milk and dairy products. Processed foods and hydrogenated fats should be avoided to reduce trans fatty acid intake. Unless children are very active, total fat intake should be in the range of 30 –35% of total energy. The argument put forward for a restricted total lipid intake in young children is the prevention of adult-onset cardiovascular disease. This effect depends on the reduction of saturated and trans-monounsaturated fats but not total lipids. There is no firm basis to promote low total-fat intakes in children with normal body weight during the first years of life. The balance in (n-6) to (n-3) total fatty acid intake is based on eicosanoid-related effects (Fig. 2). There are indications that variations of the ratio of (n-6) to (n-3) modulate allergy, inflammation, clotting and vascular responses. The provision of preformed LCPUFA has been suggested for nonbreast-fed infants for the first 6 mo of life. For now, there is no evidence for a need of preformed LCPUFA after age 6 mo in infants who were fully breast-fed TABLE 5 Dietary composition of fat supply for children older than 2 y for the prevention of nutrition related chronic disease Dietary component Recommended factors1 Total dietary fat intake Saturated fatty acids Polyunsaturated fatty acids (n-6) PUFA (n-3) PUFA (n-6) to (n-3) ratio Monounsaturated fatty acids Cholesterol Antioxidant vitamins Potentially toxic factors2 Trans fatty acids Erucic acid Lauric and myristic acids Cyclopropenoids Hydroperoxides
Amount
30–40% of energy depending on activity ⱕ10% of energy (mainly C12, C14, C16) 5–15% of energy 4–13% of energy 1–2% of energy 5:1 to 10:1 no restriction within limits of total fat ⬍about 300 mg/d generous intake desirable ⬍2% of total energy ⬍1% of total fat ⬍10% of total fat Traces Traces
1 May be considered after age 6 mo for infants at high risk of cardiovascular disease who are living in a clean environment with low prevalence of infection. 2 Limit processed foods and hard fats and hard margarine as a practical way to limit intake of saturated and trans fatty acids.
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for the first 6 mo of life and receive variety of foods including soy oil, egg yolk, liver and fish. Lipids are important determinants of growth and body composition, necessary for absorption of fat-soluble vitamins, a key dietary determinant of prostanoid metabolism and related functions, a structural component of cell membranes in all vital organs and a source of EFA required for normal neurodevelopment. LITERATURE CITED 1. Uauy, R. (1990) Are Omega-3 fatty acids required for normal eye and brain development in the human?. J. Pediatr. Gastroenterol. Nutr. 11: 296 –302. 2. Uauy, R., Mena, P. & Valenzuela, A. (1999) Essential fatty acids as determinants of lipid requirements in infants, children and adults. Eur. J. Clin. Nutr. 53(Suppl 1): S66 –S77. 3. Beare-Rogers, J., Ghafoorunissa, A., Korver, O., Rocquelin, G., Sundram, K. & Uauy, R. (1998) Dietary fat in developing countries. Food Nutr. Bull. 19: 251–266. 4. Koletzko, B., Tsang, R., Zlotkin, S. H., Nichols B., Hansen J. W., eds. (1997) Importance of dietary lipids. In: Nutrition during Infancy. Principles and Practice. 1st ed. pp. 123–153, Digital Educational Publishing, Cincinnati, OH. 5. Uauy, R., Mize, C. & Castillo-Dura´ n, C. (2000) Fat intake during childhood: metabolic responses and effects on growth. Am. J. Clin. Nutr. 72(Suppl.): 1354S–1360S. 6. Uauy, R. & Mena, P. (2001) Lipids and neurodevelopment. Nutr. Rev. 59: S34 –S48. 7. Uauy, R., Mena, P. & Rojas, C. (2000) Essential fatty acids in early life: structural and functional role. Proc. Nutr. Soc. 59: 3–15. 8. Innis, S. M. (1991) Essential fatty acids in growth and development. Prog. Lipid Res. 30: 39 –103. 9. Food and Agriculture Organization of the United Nations (1980) Dietary fats and oils in human nutrition. Rome: FAO, Publications Division. 10. FAO/WHO Report of a Joint Expert Consultation (1994) Fats and oils in human nutrition. FAO Food and Nutrition Paper # 57. Rome: Food and Agricultural Organization; pp. 49 –55. 11. Bernback, S., Blackberg, L. & Hernell, O. (1990) The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic co-lipase-dependent lipase, and bile salt stimulated lipase. J. Clin. Invest. 85: 1221–1226. 12. Chappell, J. E., Clandinin, M. T., Kearney-Volpe, C., Reichmann, B. & Swyer, P. W. (1986) Fatty acid balance studies in premature infants fed human milk or formula: effect of calcium supplementation. J. Pediatr. 108: 439 – 447. 13. Jensen, R. G. (1989) The lipids of human milk. CRC Press, Boca Raton, FL. 14. Filer, L. J., Mattson, F. H. & Fomon, S. J. (1969) Triglyceride configuration and fat absorption in the human infant. J. Nutr. 99: 293–298. 15. Ockner, R. K., Hughes, F. B. & Isselbacher, K. J. (1969) Very low density lipoproteins in intestinal lymph: role in triglyceride and cholesterol transport during fat absorption. J. Clin. Invest. 48: 2367–2373. 16. Ockner, R. K. & Jones, A. L. (1970) An electron microscopic and functional study of very low density lipoproteins in intestinal lymph. J. Lipid Res. 11: 284 –292. 17. Weintraub, M. S., Zechner, R., Brown, A., Eisenberg, S. & Breslow, J. L. (1988) Dietary polyunsaturated fats of the w-6 and w-3 series reduce postprandial lipoprotein levels. Chronic and acute effects of fat saturation on postprandial lipoprotein metabolism. J. Clin. Invest. 82: 1884 –1893. 18. Brown, M. S., Herz, J., Kowal, R. C. & Goldstein, J. L. (1991) The low-density receptor-related protein: double agent or decoy? Curr. Opin. Lipidol. 2: 65–72. 19. Spady, D. K. & Woollett, L. A. (1990) Interaction of dietary saturated and polyunsaturated triglycerides in regulating the processes that determine plasma low density lipoprotein concentrations in the rat. J. Lipid Res. 31: 1809 – 1819. 20. Mize, C. E., Uauy, R., Kramer, R., Benser, M., Allen, S. & Grundy, S. M. (1995) Lipoprotein-cholesterol responses in healthy infants fed defined diets from ages 1 to 12 months: comparison of diets predominant in oleic acid versus linoleic acid, with parallel observations in infants fed a human milk based diet. J. Lipid Res. 36: 1178 –1187. 21. ESPGAN Committee on Nutrition, Aggett, P. J., Haschke, F., Heine, W., Hernell, O., Koletzko, B., Lafeber, H., Ormission, A., Rey, J. & Tormo, R. (1994) Committee Report: childhood diet and prevention of coronary heart disease. J. Pediatr. Gastroenterol. Nutr. 19: 261–269. 22. Sprecher, H. (2000) Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim. Biophys. Acta. 1486: 219 –231. 23. Salem, N., Wegher, B., Mena, P. & Uauy, R. (1996) Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc. Nat. Academ. Sci. USA 93: 49 –54. 24. Uauy, R., Mena, P., Wegher, B., Nieto, S. & Salem, N. (2000) Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth. Pediatr. Res. 47: 127–135. 25. Tsang, R. C., Lucas, A., Uauy, R. & Zlotkin, S. H. (eds.) (1993) Nutri-
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