Milk – The promoter of chronic Western diseases
Section snippets
Insulin and the insulin-like growth factor system
The insulin-like growth factor (IGF) system is essential for normal embryonic and postnatal growth, and plays an important role in the function of a healthy immune system, lymphopoiesis, myogenesis and bone growth among other physiological functions. Growth hormone (GH) and IGFs play an important role in growth and tissue homeostasis. GH secreted by the anterior pituitary binds to GH receptor, expressed on most peripheral cells of the body. In peripheral tissues and predominantly in the liver,
Milk and milk protein consumption increase IGF-1 serum levels
Milk is a complex, bioactive substance honed by evolution to promote growth and development of the infant mammal. Cow’s milk and dairy products derived from milk are widely consumed by children and adults of Western societies well after the age of weaning. It is important to note that cow’s milk contains active IGF-1 (4–50 ng/ml) and IGF-2 (40–50 ng/ml) [3], [4]. IGF-signalling belongs to the canonical pathways and networks regulated by estrogen and placental GH in the bovine mammary gland. Cows
The insulinotropic effect of milk and milk products
Fermented and non-fermented milk products give rise to insulinaemic responses far exceeding what could be expected from their low glycaemic indexes (GI). Despite low GIs of 15–30, milk products produce three to sixfold higher insulinaemic indexes (II) of 90–98 [17]. A large and similar dissociation of the GI and II exists for both whole milk (GI: 42 ± 5; II: 148 ± 14) and skim milk (GI: 37 ± 9; II: 140 ± 13) [18]. It has been suggested that some factor within the protein fraction of milk is responsible
Differential induction of insulin and IGF-1 by milk protein fractions
The major protein fractions of cow’s milk is casein (80%), the remaining 20% are whey proteins. Both, whey and casein contain specific proteins and peptides that may have growth stimulating effects. The effect of whey and casein fractions of milk on fasting concentrations of IGF-1 and insulin has been examined in 57 eight-year-old boys who received over seven days either casein or whey protein fractions with protein amounts of casein or whey similar to the content of 1.5 l skim milk. In the
Insulin induces hepatic synthesis and secretion of IGF-1
The main source of circulating IGF-1 is considered to be the liver. A study of seven insulin-dependent diabetic patients in whom insulin was withheld for 12 h received insulin infusions (1.6 mU insulin/kg/min) after an overnight fasted state. Serum IGF-1, but not IGFBP-3, significantly increased during the insulin infusion, whereas hepatic IGFBP-1 synthesis was reduced [26]. Mean serum baseline levels of IGF-1 in arterial blood (166 μg/l) and hepatic vein (160 μg/l) blood increased during the 180
The impact of milk consumption on fetal growth
Both IGF-1 and IGF-2 are expressed in fetal tissues from the earliest stage of pre-implantation to the final phase of tissue maturation before birth. IGF-2 is the primary growth factor supporting embryonic growth, with IGF-1 increasing in importance later in gestation. Concentrations of IGF-1 in the fetus are affected by nutrient supply to the fetus and nutrient-sensitive hormones [27]. Insulin positively regulates IGF-1 levels [28]. In industrialized countries, one of 10 newborns is affected
Early programming of the GH-IGF-1 axis
The GH-IGF-1 axis is closely related to feeding in the newborn [37]. More recent data point to an early programming of the IGF-1 axis within the first months of live. In early pregnancy maternal endocrine IGF-1 programs the placenta for increased functional capacity throughout gestation [38]. IGFs play a critical role in fetal and placental growth throughout gestation [27], [39]. Increased maternal milk consumption during pregnancy enhances the nutrient supply for the fetus by an enlarged
Milk consumption shifts the GH-IGF-1 axis in pre-pubertal children
After a month of drinking 710 ml of ultra-heat treated whole milk daily, 10–11-year-old Mongolian children, previously not used to milk consumption, had a higher mean plasma level of IGF-1 and higher ratio of IGF-1/IGFBP-3 [41]. The mean serum IGF-1 levels were raised in the children after 4 weeks of milk consumption by 23.4% from mean pre-treatment values of 291–358 ng/ml [41]. There is good evidence that milk consumption shifts the human intrinsic IGF-1 axis to unusual high levels.
Milk consumption and linear growth
Over the last centuries, body height significantly accelerated. Milk intake is the best source for utilization of calcium for bone growth and mineralization and is positively associated with IGF-1 serum levels [15]. Milk consumption during pregnancy is associated with increased infant size at birth [29]. During a four-week intervention with daily milk intake of 710 ml, Mongolian children experienced a rapid linear growth (the equivalent of 12 cm/year). Girls grew a mean 1.1 + 0.2 cm and boys 1.0 + 0.2
Effect of IGFs and insulin on adreno-gonadal maturation and onset of puberty
The GH–IGF-1 axis plays an important role for the ACTH-dependent production of dehydroepiandrosterone sulphate (DHEAS) of the human adrenal gland [44]. IGF-1 is involved in ovarian androgen synthesis and has been implicated in the pathogenesis of ovarian hyperandrogenism and polycystic ovary syndrome (PCOS) [45]. IGF-1 serum levels are increased in patients with PCOS who exhibit insulin resistance, anovulation, hyperandrogenism with acne and hirsutism. Proliferation and differentiation of adult
Milk consumption, IGF-1 serum levels and acne
Acne is regarded as an androgen-dependent disease of the pilosebaceous follicle. Its course, however, corresponds less closely to plasma androgen levels than it does to GH and IGF-1 levels [53]. Significantly increased serum levels of IGF-1 have been observed in women with post-adolescent acne as well as adult acne patients [54], [55]. In women, the total number of acne lesions correlated with serum IGF-1 levels. In Western societies, acne is a nearly universal disease afflicting 79–95% of the
Endocrine disorders associated with increased IGF-1 serum levels and acne
In pre-pubertal girls with premature adrenarche significantly higher ACTH-stimulated 17-hydroxy-pregnenolone and DHEA serum levels, high IGF-1, and low IGFBP-1 have been reported [62]. It is remarkable, that premature pubarche shares many clinical characteristics with PCOS [62]. PCOS is associated with increased serum levels of IGF-1 and DHEAS, hyperinsulinemia, insulin resistance, acne and hirsutism [63]. Twofold elevated serum levels of free IGF-1 have been detected in women with PCOS [63].
Milk consumption and obesity
IGF-1 is required for terminal differentiation of pre-adipocytes into adipocytes [65], [66]. Milk consumption during pregnancy increased infant size and birth weight [29], [30]. Data from the Danish National Birth Cohort (n = 50,117) demonstrate a significant association between increase in birth weight and quantified intakes of protein from dairy products [29].Umbilical cord serum IGF-1 concentrations were higher in LGA newborns compared to AGA and SGA newborns [34]. Umbilical cord serum IGF-1
Postnatal IGF-1 axis, diabetes mellitus and hypertension
The IGF-1 axis may be programmed by diet early in infancy [40]. An inverse relation between IGF-1 levels during the first months of life and IGF-1 levels in adulthood could be observed in 109 infants of the observational Copenhagen cohort study [40]. Low levels of IGF-1 in the postnatal period are associated with high IGF-1-levels in adolescence. Low levels of IGF-1 are reported in SGA newborn infants [34]. Low birth weight is a recognized risk factor for the development of type 2 diabetes and
Milk, insulin, IGF-1 and cancer
IGF-1 is a known mitogenic hormone that stimulates growth, differentiation and metabolism in a variety of cell types [81]. IGF-1 participates in the regulation of the cell cycle, inhibiting the processes of apoptosis and stimulating cell proliferation. IGF-1 is a potential tumour promoter [82]. Several studies demonstrated a link between increased IGF-1 serum levels with increased risk of breast, prostate, colorectal, and lung cancer [83]. High expression of IGF1Rs has been detected in the
Milk consumption in pregnancy, birth weight and risk of breast cancer
Milk consumption during pregnancy increases maternal IGF-1 serum levels, birth weight and height of the newborn [29], [42], [43], all known risk factors of breast cancer [98], [99]. The intrauterine environment might contribute to the predisposition of women for breast cancer in adulthood [100]. The responsible in-utero-mechanism has been linked to IGF-1 [101]. Thus, the environmental breast cancer-promoting factor of Western societies could be associated with milk-induced IGF-signalling during
Milk, IGF-1 and cardiovascular disease
The association between milk consumption and mortality from ischemic heart disease has been suggested in this journal 25 years ago [106]. A linear correlation between the consumption of unfermented milk proteins and male mortality of coronary heart disease has been demonstrated [107]. Animal models have shown that IGF-1 is involved in stimulating atherosclerosis [108], [109]. IGF1Rs are abundant in vascular smooth muscle cells and factors that stimulate atherosclerosis, such as angiotensin II
IGF-1 signalling and neurodegenerative diseases
The major risk factor for the development of neurodegenerative disease is aging [112]. Mechanistic links between the aging process and toxic protein aggregation, a common hallmark of neurodegenerative diseases, has been revealed. Lifespan is regulated by at least three different mechanisms, one of which is the insulin/IGF-1 signalling pathway. The insulin-IGF-1 pathway is the major candidate to link aging, proteotoxicity and late-onset neurodegenerative disease [113], [114]. It has been
The IGF-axis and allergic and autoimmune disorders
The thymus is the only organ specialized in the establishment of immunological self-tolerance and stands at the crossroads between the immune and neuroendocrine systems [116]. The neuroendocrine system regulates the process of T-cell differentiation from the very early stages. T lymphocytes undergo in the thymus a complex educative process that establishes central T-cell self-tolerance of neuroendocrine principle. Neuroendocrine self-antigens correspond to peptide sequences that have been
Discussion and hypothesis
Our “inborn belief” of the beneficial effect of cow’s milk in human nutrition is challenged. Humans are the only species on earth allowed to consume milk, an evolutionary designed sophisticated growth-signalling system, lifelong after weaning. Cow’s milk consumption and most likely other dairy products have an enormous impact on the human GH/insulin/IGF-1 axis, disturbing most sensitive hormonal regulatory signalling networks, interfering with IGF1R-signalling from fetal life to senescence (
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Oxidative stress and metabolic syndrome in acne vulgaris: Pathogenetic connections and potential role of dietary supplements and phytochemicals
2023, Biomedicine and PharmacotherapyNon-conventional therapeutical approaches to acne vulgaris related to its association with metabolic disorders
2022, European Journal of PharmacologyCitation Excerpt :The concentration of IGF-1, the number of acne lesions, the degree of sebum secretion, dihydrotestosterone (DHT), and dehydroepiandrosterone sulfate were all proved to have greater values in acne patients. IGF-1 stimulates 5α-reductase, which is located in the adrenal glands and gonads with impact on androgen receptor signal transduction, androgen production, fat metabolism, and the rapid increase in sebocyte levels (Arora et al., 2011; Melnik, 2009). Sebum production increases as a result of androgens and IGF-1, being one of the most important acne risk factors (Bowe et al., 2010).
Development and single laboratory validation of a targeted liquid chromatography-triple quadrupole mass spectrometry-based method for the determination of insulin like growth factor-1 in different types of milk samples
2022, Food Chemistry: XCitation Excerpt :Mammals produce structurally highly similar IGF-1 and the bovine and human molecules have the same amino acid sequence (Juskevich & Guyer, 1990), therefore bovine IGF-1 can bind to the human IGF receptor (Francis, Upton, Ballard, McNeil, & Wallace, 1988). In addition, IGF-1 remains active in serum after milk consumption because IGF-1 digestion in the gut is being protected by milk’s proteins (Melnik, 2009). Interestingly, it’s the hepatic IGF-1 production stimulation via amino acid transfer induced by milk that increase the consumer’s serum IGF-1 level (Melnik, John, & Schmitz, 2013).