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Abstract Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.

Milk is rich in miRNAs that appear to play important roles in the postnatal development of all mammals. Currently, two competing hypotheses exist: the functional hypothesis, which proposes that milk miRNAs are transferred to the offspring and exert physiological regulatory functions, and the nutritional hypothesis, which suggests that these molecules do not reach the systemic circulation of the milk recipient, but merely provide nutrition without conferring active regulatory signals to the offspring. The functional hypothesis is based on indirect evidence and requires further investigation. The nutritional hypothesis is primarily based on three mouse models, which are inherently problematic: 1) miRNA-375 KO mice, 2) miRNA-200c/141 KO mice, and 3) transgenic mice presenting high levels of miRNA-30b in milk. This article presents circumstantial evidence that these mouse models may all be inappropriate to study the physiological traffic of milk miRNAs to the newborn mammal, and calls for new studies using more relevant mouse models or human milk to address the fate and role of milk miRNAs in the offspring and the adult consumer of cow's milk. [ABSTRACT FROM AUTHOR]

Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual's pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. [ABSTRACT FROM AUTHOR]

The normal low-density lipoprotein (LDL) cholesterol range is 50 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl. No major safety concerns have surfaced in studies that lowered LDL to this range of 50 to 70 mg/dl. The current guidelines setting the target LDL at 100 to 115 mg/dl may lead to substantial undertreatment in high-risk individuals. [Copyright &y& Elsevier]

Purpose: To explore the possibility that a Palaeolithic diet, i.e. one that corresponds to what was available in any of the ecological niches of pre-agricultural humans (1.5 million-10,000 years bp ), is optimal in the prevention of age-related degenerative disease. Design: Literature review. Materials and Methods: Between 1985 and December 2002, more than 200 scientific journals in medicine, nutrition, biology and anthropology were systematically screened for relevant papers. Computer-based searches and studies of reference lists in journals and books provided a vast number of additional papers. Results: Increasing evidence suggests that a Palaeolithic diet based on lean meat, fish, vegetables and fruit may be effective in the prevention and treatment of common Western diseases. Avoiding dairy products, margarine, oils, refined sugar and cereals, which provide 70% or more of the dietary intake in northern European populations, may be advisable. Atherosclerosis is highly dependent on dietary manipulation in animal experiments. Atherogenic dietary factors include fat (any type) and casein, and hypothetically cereals. Stroke, ischaemic heart disease and type 2 diabetes seem largely preventable by way of dietary changes in a Palaeolithic direction. And insulin resistance, which may have far-reaching clinical implications as a cause of unregulated tissue growth, may also respond to an ancestral diet. Conclusions: Lean meat, fish, vegetables and fruit may be optimal, rather than a strictly vegetarian diet, in the prevention of cardiovascular disease, diabetes and insulin resistance. [ABSTRACT FROM AUTHOR]

Epidemiological and experimental studies have suggested that dietary salt may play a role in airway responsiveness. We have previously shown that a low salt diet improves and a high salt diet exacerbates post-exercise pulmonary function in individuals with exercise-induced asthma. The aim of this study was to determine the influence of both elevated and restricted salt diets on pulmonary function during exercise in individuals with exercise-induced asthma. Nine men and six women participated in this double-blind, crossover study. The participants entered the study on their normal salt diet and were placed on either a low or high salt diet for 2 weeks. Each diet was randomized, with a 1 week washout period between diets before crossing over to the alternative diet for 2 weeks. The participants underwent treadmill testing at 85% of their age-predicted heart rate on the normal salt diet and at the end of each treatment period. Pulmonary function was assessed during exercise by arterial saturation (ear oximetry) and indirect calorimetry. Twenty-four hour urine collections confirmed compliance with the diets. Arterial saturation was reduced on the high and improved on the low salt diet at higher exercise intensities. Tidal volume and frequency selection during exercise varied with the diets, with a higher tidal volume and lower frequency on the high salt diet, but a lower tidal volume and higher frequency on the low salt diet. This suggested greater airway resistance during the high salt diet. In conclusion, the low salt diet improved and the high salt diet exacerbated pulmonary function during exercise in individuals with exercise-induced asthma. The mechanism of action remains unclear. [ABSTRACT FROM AUTHOR]

Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice versa, the nature of this relationship remains elusive. In the present review, we provide evidence for how the interaction of dietary lectins with enterocytes and lymphocytes may facilitate the translocation of both dietary and gut-derived pathogenic antigens to peripheral tissues, which in turn causes persistent peripheral antigenic stimulation. In genetically susceptible individuals, this antigenic stimulation may ultimately result in the expression of overt rheumatoid arthritis (RA) via molecular mimicry, a process whereby foreign peptides, similar in structure to endogenous peptides, may cause antibodies or T-lymphocytes to cross-react with both foreign and endogenous peptides and thereby break immunological tolerance. By eliminating dietary elements, particularly lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RA. [ABSTRACT FROM PUBLISHER]