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Leche y Crecimiento
Leche y Crecimiento
Leche y Crecimiento
a The
Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes,
Schneider Children’s Medical Center of Israel, Petach Tikva, Israel; b Sackler Faculty of Medicine, Tel Aviv University,
Tel Aviv, Israel; c Felsenstein Medical Research Center, Petach Tikva, Israel
Keywords Introduction
Milk proteins · Linear growth · Catch-up growth · Bone
health · Weight gain · Body composition Mammalian milk has been engineered by evolution to
supply all nutrients and energy required to foster proper
postnatal growth and development of infants in the post-
Abstract natal period. Although in many societies, milk and milk
Milk has long been recognized to constitute a complete, products of various domestic sources form an important
well-balanced source of the nutrients and energy required part of the local diet, in many others they do not, and be-
to ensure the proper postnatal growth and development of yond infancy, the growing child may not receive any form
infants. A growing body of evidence suggests the positive of milk.
effects of dairy products and particularly of milk proteins on While the benefits of milk and its products have in
linear growth also in older children, both healthy or during general long been recognized, the full picture of what
recovery from malnutrition. This evidence led the way to the makes milk so effective remains to be elucidated.
performance of extensive research aimed to delineate the A growing body of evidence has suggested the positive
components of milk and the mechanisms acting to make effects of dairy products and milk proteins on linear
milk so effective. The present review summarizes the current growth in children, and in recent years, many researchers
knowledge regarding the influence of milk and its proteins have focused upon the question of just what makes milk
on linear growth in healthy and malnourished children, fo- so effective. The present review presents the current
cusing also on other important aspects of healthy growth, knowledge on the identity of the most important compo-
including bone health, weight status, and body composi- nents of bovine milk and summarizes the results of recent
tion. © 2017 S. Karger AG, Basel studies performed in children or animals, which have in-
vestigated the effect of milk on linear growth, focusing on
bone health, weight status, and body composition.
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E-Mail karger@karger.com
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In general, milk and dairy foods are considered to be a recent extensive ecological study analyzed the main cor-
good, balanced source of nutrients supporting healthy relates of male height in 105 countries in Europe, Asia,
growth, providing proteins, vitamins (A, D, E, and B North Africa, and Oceania [14]. Data on male height were
complex vitamins such as thiamine and riboflavin), and compared with the average consumption of protein from
minerals (calcium, phosphorus, magnesium, zinc, and se- 28 different sources and with 7 socioeconomic indicators.
lenium) [1]. Other components such as specific sugars The most significant nutritional correlates of stature were
and bioactive peptides may have an active role, beyond intake of milk proteins (r = 0.79; p < 0.001), followed by
their role as building blocks. total protein (r = 0.74; p < 0.001), and animal protein (r =
In the human diet, milk is an important source of high- 0.73; p < 0.001); while the most negative nutritional cor-
quality proteins, supplying approximately 32 g protein/L relate in the total sample was rice protein (r = –0.74; p <
[1]. Milk proteins include 2 main fractions: whey and ca- 0.001). The highest correlation with height (r = 0.85; p <
sein. Whey (20% of the milk protein) is the water-soluble 0.001) was achieved for the combination of proteins from
fraction comprising several globular proteins, including milk products, eggs, pork and beef meat, and potatoes.
beta-lactoglobulin, alpha-lactalbumin, albumin and oth- The authors identified 3 primary types of diets based on
ers, and is especially rich in branched-chain amino acids the major source of protein. The first, a rice protein-based
(leucine, isoleucine, valine, and lysine) as well as sulfur- diet, characterized by a very low protein and energy con-
containing amino acids. Casein (80% of the milk proteins) sumption, is typical of tropical Asia, and is associated
consists of a family of water-insoluble phosphoproteins [2] with a very short stature (162–168 cm). The second, a
and is characterized by a higher proportion of histidine, wheat-based diet with a high plant-protein content, char-
methionine, phenylalanine, and proline [1, 3, 4]. However, acterized by a relatively high total protein and energy
both whey and casein are classified as high-quality proteins consumption (comparable with that of European coun-
and are frequently graded as the best protein source ac- tries), is typical of the Muslim countries of North Africa
cording to their essential amino acid score and protein di- and the Near East, and is associated with a relatively short
gestibility-corrected amino acid score [1]. Casein also af- stature (average male height <174 cm). The third, an ani-
fects growth by increasing calcium absorption from the mal protein-based diet consisting mostly of milk pro-
intestine, leading to greater bone mineralization [5]. teins, is typical of Northern and Central Europe, and is
The carbohydrate fraction of bovine milk is divided associated with the tallest mean stature in the world (>180
into lactose (48 g/L), free oligosaccharides (0.05 g/L) [6], cm). Most importantly, these data showed a difference of
and bound glycans or glycoconjugates present in milk some 10 cm (174 vs. 184) between nations relying on
glycolipids and glycoproteins [7]. Casein and whey differ plant versus animal proteins, despite a comparable con-
in their glycoprotein content. For example, the glycosyl- sumption of total protein and energy. This indicates that
ated lactoferrin (LF; a member of the transferrin family), plant-based diets do not provide the optimal stimuli for
an iron and Ca2+-binding protein present in the whey physical growth, even when protein and energy intakes
protein fraction [8], was found to be an important physi- are adequate.
ological regulator of bone growth [9–11]. Furthermore, a A recent meta-analysis of 12 studies conducted on
recent publication has shown the specific effects of oligo- children aged 3–13 years in Europe, USA, China, North-
saccharides released from milk glycoproteins on bacterial ern Vietnam, Kenya, Indonesia, and India, found a posi-
growth [12], providing a possible explanation as to the tive effect of milk products on linear growth, with an ef-
effect of milk on gut microbiome composition. fect size of 0.4 cm/year per daily portion of 245 ml of milk
In the following sections, we will address the influence [13]. In addition, the meta-regression analysis indicated
of milk and its proteins on linear growth in healthy and that milk per se might have a greater effect on growth than
malnourished children, focusing on bone health, weight, other dairy products; lower height-for-age and being a
and body composition. teenager increased the effect. One of the main limitations
of this systematic review is that most of the studies had a
short-term follow-up, typical of most clinical trials. This
The Effect of Milk and Its Proteins on Linear Growth limits the knowledge of the cumulative effect of dairy
product consumption on adult stature. In this regard, co-
Milk and dairy products play an important role in ex- hort studies, although more vulnerable to bias than clini-
plaining historical trends or regional differences in hu- cal trials, can be helpful. A prospective cohort study of
man height during the 19th and 20th centuries [13]. A pre-menarcheal girls aged ≥9 years in the USA (n = 5101;
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Univ. of California San Diego
How Milk and Its Proteins Affect Growth, Horm Res Paediatr 3
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pressed by a lesser decrease in mid-upper arm circumfer- cium on bone mineral content (BMC), showed a statisti-
ence and hemoglobin levels. These findings suggest that cally nonsignificant increase of 2 g in the BMC of children
increasing the dairy protein content of such supplements who had received a diet supplemented by dairy products
may protect children from wasting and anemia [24]. or dietary calcium as compared to controls [35]. How-
A double-blind RCT found that malnourished tod- ever, the data were very heterogeneous with respect to
dlers (aged 6–59 months, n = 2230) receiving a whey- baseline calcium intake. Among participants with normal
based RUSF showed better nutritional recovery than tod- or near-normal baseline dietary calcium/dairy intakes,
dlers receiving a soy-based RUSF, even though the whey supplemental dairy/calcium showed little impact on
RUSF contained 33% less total protein and provided ap- BMC. The 3 studies found to contribute most (over 75%)
proximately 8% less energy [25]. This important study to the heterogeneity [36–38] included subjects with low
presented the first specific evidence of the advantage of baseline calcium intakes, well below the recommended
whey proteins in treating moderate acute malnutrition levels. The combined analyses of these reports yielded a
[25]. In previous studies reporting positive correlations significant increment in the mean BMC of 49 g (95% CI:
between the consumption of dairy protein and improved 24.0–76.6; n = 1,183). While the authors of this meta-
outcomes in malnourished children, it was unclear analysis concluded that increasing dietary calcium/dairy
whether these results were attributable to the quality of products significantly increased total BMC in children
the proteins or to the total amounts of protein consumed with low baseline intakes [35], it was not possible to dis-
[22–24, 26, 27]. tinguish the effects of calcium from that of other compo-
These data suggest that milk proteins may have an im- nents of dairy products, such as high-quality proteins, vi-
portant role in rehabilitation from malnutrition and in tamins C, D, and K, or minerals such as copper, manga-
CU growth. However, further studies are needed to deter- nese, and zinc, which are also thought to influence bone
mine the best composition (quality and source) and matrix production and maintenance [1, 39]. Further-
quantity of proteins required to match the physiological more, calcium bioavailability and absorption of calcium
demands of children during CU growth. may be influenced and optimized by the presence of milk
proteins and lactose, as well as the ratio of calcium to
phosphorus [1, 40, 41].
The Influence of Milk and Its Proteins on Bone Health A subgroup of children with low dairy and calcium in-
take comprises those children with IgE-mediated cow’s
Low bone mass is the main risk factor for osteoporosis milk allergy (IgE-CMA). A study by Nachshon et al. [42]
and fractures. It is well established that the peak bone found a significant reduction in BMD and peak bone
mass achieved during childhood and adolescence will de- mass after long-term dairy avoidance in young adults
termine bone mass in later life [1, 28, 29]. Bone mass is with IgE-CMA. Of particular note was their finding that
acquired relatively slowly throughout childhood, but IgE-CMA patients who had completed an oral immuno-
with the onset of puberty and the growth spurt in height, therapy program and had been on unlimited dairy intake,
bone mineral accretion is rapid, reaching a peak shortly routinely tolerating at least 4.5 g cow’s milk proteins dur-
after peak height gain at 12.5 ± 0.9 years in girls and 14.1 ing 12–39 months before BMD analysis, had significantly
± 1.0 years in boys of European ancestry [30]. Within 4 higher BMD T and Z scores at all measured sites (hip,
years following this peak, 95% of the adult bone mass is femoral neck, and lumbar spine) than the IgE-CMA pa-
achieved [31]. This period of rapid accretion may be a tients avoiding cow’s milk proteins, with no significant
time of both opportunity and vulnerability for optimizing differences between the allergic patients who recently had
peak bone mass [32]. The attainment of peak bone mass begun to consume milk and the healthy controls.
is affected by multiple factors, including genetics and nu- In 2016, the National Osteoporosis Foundation of the
tritional and lifestyle factors [32–34]. Lifestyle choices, US issued a scientific statement to provide evidence-
including diet and physical activity, influence 20–40% of based guidelines for achieving maximal peak bone mass
the adult peak bone mass [32]; thus, optimization of life- early in life, based on a systematic review of the literature
style factors is an important strategy for achievement of [32]. Analysis of the effect of various lifestyle parameters,
the maximal bone mass to reduce the risk of osteoporosis e.g., nutrition and physical activity, on bone mass devel-
[32]. opment in youth indicated a positive effect of calcium
A meta-analysis of 21 RCTs aimed to determine the intake and of physical activity, especially during late
impact of dietary intake of milk products and dietary cal- childhood and the peripubertal years (grade A evidence),
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How Milk and Its Proteins Affect Growth, Horm Res Paediatr 5
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and bone health similar to that achieved by re-feeding bone and linear growth in healthy as well as malnourished
with casein, but with a lesser weight gain. These results children? Do the effects on weight status and the risk of
suggest that a whey-based diet may circumvent long-term obesity differ in infancy and later childhood? What are
obesogenic complications of catch-up (CU) growth. the mechanisms by which milk components influence
However, it is too early to translate these data into clinical body composition and height and weight gain? Further
recommendations for humans. clinical and laboratory studies are required to answer
these questions.
Conclusion
Acknowledgment
A growing body of evidence supports the positive ef-
The authors are grateful to Ruth Fradkin for the English edit-
fects of milk proteins on linear growth in healthy chil-
ing.
dren, as well as on CU growth during recovery from mal-
nutrition. However, many questions remain to be an-
swered. What is the ideal amount of milk proteins required
Disclosure Statement
to promote healthy bone and linear growth in healthy as
well as malnourished children? What is the ideal ratio be- All authors state that they have no conflicts of interest to dis-
tween milk proteins (whey and casein) to promote healthy close.
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