Milk and Milk Products in Human Nutrition

R. A. Clemens, O. Hernell, K. F. Michaelsen

• Publisher: S. Karger
• Year: 2011
• ISBN:
  9783805595872
• Topic: Medicine
• Subtopic: Perinatology & Neonatology

Milk, the first and for a time only source of nutrition for mammals, influences early growth and development and may provide a foundation for health throughout the entire lifespan. It is therefore mandatory that milk substitutes have a composition which fulfills the same goals and confers as close as possible the overall health benefits of human milk. Moreover, in many populations, milk continues to play a major role in a healthy and balanced diet throughout life: During childhood, pregnancy and adulthood, intake of cow's milk has important beneficial effects on linear growth, bone development and the risk of developing caries, and it is important in the prevention and treatment of undernutrition in low-income countries.This publication contains the presentations and discussions of the Nestlé Nutrition Institute Workshop held in Marrakech in March 2010. It focuses on three main topics: milk during pregnancy and infancy, milk during childhood in low- and high-income countries, and general aspects of milk in adult nutrition. Together, these contributions cover most aspects of milk during the life cycle in a global perspective, making the publication a comprehensive textbook.

Clemens RA, Hernell O, Michaelsen KF (eds): Milk and Milk Products in Human Nutrition.
Nestlé Nutr Inst Workshop Ser Pediatr Program, vol 67, pp 79–97,
Nestec Ltd., Vevey/S. Karger AG, Basel, © 2011.

Milk and Linear Growth: Programming of the IGF-I Axis and Implication for Health in Adulthood

Richard M. Martin^a,b, Jeff M.P. Holly^c, David Gunnell^a

^aDepartment of Social Medicine, ^bMRC Centre for Causal Analysis in Translational Epidemiology, Department of Social Medicine, and ^cClinical Sciences North Bristol, University of Bristol, Bristol, UK

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Abstract

There is increasing awareness that childhood circumstances influence disease risk in adulthood. As well as being strongly influenced by genes/genetic factors, stature acts as a marker for early-life exposures, such as diet, and is associated with risk of several chronic diseases in adulthood. Stature is also a marker for levels of insulin-like growth factor (IGF)-I in childhood. Levels of IGF-I are nutritionally regulated and are therefore modifiable. Milk intake in childhood and in adulthood is positively associated with higher levels of circulating IGF-I and, in children, higher circulating IGF-I promotes linear growth. Studies conducted by our team and others, however, indicate that the effect of milk is complicated because consumption in childhood appears to have long-term, programming effects which are opposite to the immediate effects of consuming milk. Specifically, studies suggest that the long-term effect of higher levels of milk intake in early childhood is opposite to the expected short-term effect, because milk intake in early-life is inversely associated with IGF-I levels throughout adult life. We hypothesize that this long-term programming effect is via a resetting of pituitary control in response to raised levels of IGF-I in childhood. Such a programming effect of milk intake in early life could potentially have implications for cancer and ischemic heart disease risk many years later.

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Copyright © 2011 Nestec Ltd., Vevey/S. Karger AG, Basel

Introduction

The opportunities to directly examine the relationship between early nutrition and diseases in adulthood are limited because few cohort studies have information from birth until old age. To date, therefore, most epidemiological studies investigating early life origins of chronic diseases have used indirect markers of childhood nutritional exposures (for example, birthweight, height and leg length) and their relation with outcomes such as cancer, diabetes and ischemic heart disease [1]. Taller individuals generally have an increased risk of developing cancer [2] and a reduced risk of insulin resistance and ischemic heart disease [3]. There is some evidence that these associations may be specific to the leg length component of stature [2, 4]. Peak growth in leg length is prepubertal while peak growth in trunk is postpubertal [1]. This is demonstrated by changes in the trunk length:height ratio during growth. At birth, the ratio of trunk length to total height is approx 0.66, but by puberty it has declined to 0.52 [1]. From puberty, linear growth occurs equally in the trunk and legs. Stronger associations of adult chronic diseases with leg length have led to speculation that exposures which influence prepubertal long bone growth (e.g. early diet) may be more important in determining adult chronic disease risk [1, 5].

It has been hypothesized that influences of diet in childhood on the insulin-like growth factor (IGF) system may contribute to stature-chronic disease associations [6–9]. IGF-I in childhood is raised in response to some aspects of diet, particularly cow's milk and dairy product intake [10], and raised childhood IGF-I in turn leads to greater subsequent growth in stature [11]. There is both experimental and observational evidence that raised IGF-I levels in early life subsequently program long-term modifications in the regulation of the IGF system. The most important evidence supporting the long-term programming of the IGF system comes from a randomized controlled trial of milk supplements provided to pregnant women and their offspring up to 5 years of age [9]. In a long-term follow-up of the offspring of the mothers originally recruited to the trial, circulating levels of IGF-I were measured at age 25 years. Those offspring who received milk supplements up to age 5 years had markedly lower serum IGF-I levels when measured 20 years later. The findings are opposite to the likely immediate responses to milk supplementation, which would have been to increase hepatic production of IGF-I [10]. We have hypothesized that a relatively high IGF-I level at the time of supplementation could cause a resetting of the pituitary due to greater feedback on the growth hormone (GH) axis from the prevailing circulating IGF-I during a sensitive period of life. This long-term resetting of the pituitary to raise the threshold for stimulating GH release would result in relatively lower hepatic IGF-I production and serum levels in later life. The reverse effect would occur in response to lower nutritional intake in early life (for example, in response to breastfeeding), which would be expected to lower IGF-I levels in early life but may program, via pituitary resetting, higher observed levels in later life [8].

In this chapter, we examine evidence supporting the hypothesis for nutritional programming of IGF-I levels in response to dietary exposures in childhood and the potential long-term implications of this. Our review draws on a number of studies that the authors have been appreciably involved in, including the Boyd Orr cohort [12], the Avon Longitudinal Study of Parents and Children (ALSPAC) [10], Barry-Caerphilly Growth Cohort study [9], Prostate testing for cancer and Treatment (ProtecT) study [13] and the Promotion of Breastfeeding Intervention trial (PROBIT) [14].

Childhood Stature and Health in Adulthood

Tall adults have an increased risk of cancer [2, 13] and a lower risk of cardiovascular disease [15, 16]. Stature in childhood and adulthood is dependent on genetic as well as environmental factors. However, childhood stature may better reflect prepubertal growth influencing exposures than adult height, which reflects a combination of childhood growth and also age and duration of pubertal maturation. Recent research is beginning to identify specific periods of early growth that are important to the risk of cancer [17, 18] and cardiovascular disease [4, 19]. For cancer, the most consistent associations with childhood growth have been found in relation to breast cancer. For example, faster pubertal growth (between 8–14 years) was positively associated with incident breast cancer risk independent of final height and explained the positive association of earlier age at menarche with breast cancer [17]. This finding has support from an ecological study in Japan where rapid increases in the heights of girls year on year between 1946–1966 were paralleled by large increases in breast cancer incidence among women after a 30 year time lag (i.e. 1976–1996) [20]. Growth-influencing exposures that changed rapidly after World War II include a 20-fold increase in milk and dairy product intake in Japan [21]. Associations with childhood stature have also been found for other cancer sites, in particular colorectal cancer, prostate cancer, endometrial cancer and hematopoietic cancers [22].

In those studies that investigated associations of the components of stature and cancer, leg length (a suggested marker of exposures influencing prepubertal growth, such as early socioeconomic circumstances, infection load and nutrition [1, 5]) was the component of height most often associated with increased adult chronic disease risk. For example, in the Boyd Orr cohort, a long-term follow-up of children surveyed between 1937 and 1939 and followed up in adulthood, we found that childhood stature was inversely associated with premature cardiovascular mortality (age <65 years) and self-reported ischemic heart disease, with leg length being the component with the strongest associations [4, 23]. Associations were explained by having been breastfed and childhood socioeconomic circumstances, confirming that leg length is a proxy for these prepubertal exposures.

A previous report from the Boyd Orr cohort (based on follow-up to 1995) showed a positive association between childhood leg length and mortality from cancers unrelated to smoking [24], most obvious for fatal sex hormone-dependent cancers (breast, uterus, ovary, prostate, other genital organs): the risk of death increased by 126% for every unit increase in z score for leg length (approximately 3–4 mm). There was no evidence that trunk length was associated with cancer. A recent extended follow-up to 2004 suggested that associations were weaker than originally observed [18], although odds ratios (ORs) remained broadly consistent with a slight increase in risk with increasing childhood stature. Contrary to previously suggested stronger links with leg length [24], however, no single anthropometry measure was of particular importance in this longer-term follow-up, underlining the challenges of interpreting epidemiological data. The strongest associations were seen for breast cancer [OR per standard deviation increase in foot length: 1.16 (95% CI: 0.90–1.51); shoulder breadth: 1.16 (0.91–1.49); trunk: 1.26 (1.00–1.60)] and prostate cancer [OR for foot length: 1.22 (0.86–1.75)]. Foot length is one of the first components to reach peak growth, while shoulder breadth is one of the last [25].

Breast Milk, Cows Milk and Stature

Analysis of the Boyd Orr cohort has shown that stature was a generalized marker for many aspects of diet, housing and socioeconomic position in the children [5, 26]. The individual components of stature most strongly associated with childhood environment were leg and foot length. More specifically, leg length (but not trunk length) in both childhood and adulthood has been associated with breastfeeding in infancy in analyses of the Boyd Orr cohort [27] and in the 43-year follow-up of the 1946 UK national birth cohort [28]. The specific associat...