Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

Abstract

"The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand."

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Perinatal exposure to environmental estrogens and the development of obesity.

Abstract

"Dietary substances and xenobiotic compounds with hormone-like activity can disrupt the programming of endocrine signaling pathways that are established during perinatal differentiation. The consequences of this disruption may not be apparent until later in life but increasing evidence implicates developmental exposure to environmental hormone-mimics with a growing list of adverse health effects including reproductive problems and increased cancer risks. Obesity has recently been proposed to be yet another adverse health consequence of exposure to endocrine disrupting substances during development. There is a renewed focus on identifying contributions of environmental factors to the development of obesity since it is reaching worldwide epidemic proportions, and this disease has the potential to overwhelm healthcare systems with associated illnesses such as diabetes and cardiovascular disease. Here, we review the literature that proposes an association of perinatal exposure to endocrine disrupting chemicals, in particular those with estrogenic activity, with the development of obesity later in life. We further describe an animal model of developmental exposure to diethylstilbestrol (DES) to study mechanisms involved in programming for obesity. Our experimental data support the idea that adipocytes and the mechanisms involved in weight homeostasis are novel targets of abnormal programming of environmental estrogens, some of which are found in our foods as naturally occurring substances or inadvertently as contaminants."

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Paleolithic diets as a model for prevention and treatment of Western disease.

"Abstract

OBJECTIVES:

To explore the possibility that a paleolithic-like diet can be used in the prevention of age-related degenerative Western disease.

METHODS:

Literature review of African Paleolithic foods in relation to recent evidence of healthy nutrition.

RESULTS AND DISCUSSION:

Available evidence lends weak support in favor and little against the notion that lean meat, fish, vegetables, tubers, and fruit can be effective in the prevention and treatment of common Western diseases. There are no obvious risks with avoiding dairy products, margarine, oils, refined sugar, and cereal grains, which provide 70% or more of the dietary intake in northern European populations. If stroke, coronary heart disease, type 2 diabetes, and cancer are preventable by dietary changes, an ancestral-like diet may provide an appropriate template."

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Evaluation of biological and clinical potential of paleolithic diet

"Abstract

Accumulating evidences suggest that foods that were regularly consumed during the human primates and evolution, in particular during the Paleolithic era (2.6-0.01 x 10(6) years ago), may be optimal for the prevention and treatment of some chronic diseases. It has been postulated that fundamental changes in the diet and other lifestyle conditions that occurred after the Neolithic Revolution, and more recently with the beginning of the Industrial Revolution are too recent taking into account the evolutionary time scale for the human genome to have completely adjust. In contemporary Western populations at least 70% of daily energy intake is provided by foods that were rarely or never consumed by Paleolithic hunter-gatherers, including grains, dairy products as well as refined sugars and highly processed fats. Additionally, compared with Western diets, Paleolithic diets, based on recently published estimates of macronutrient and fatty acid intakes from an East African Paleolithic diet, contained more proteins and long-chain polyunsaturated fatty acids, and less linoleic acid. Observational studies of hunter-gatherers and other non-western populations lend support to the notion that a Paleolithic type diet may reduce the risk of cardiovascular disease, metabolic syndrome, type 2 diabetes, cancer, acne vulgaris and myopia. Moreover, preliminary intervention studies using contemporary diet based on Paleolithic food groups (meat, fish, shellfish, fresh fruits and vegetables, roots, tubers, eggs, and nuts), revealed promising results including favorable changes in risk factors, such as weight, waist circumference, C-reactive protein, glycated haemoglobin (HbAlc), blood pressure, glucose tolerance, insulin secretion, insulin sensitivity and lipid profiles. Low calcium intake, which is often considered as a potential disadvantage of the Paleolithic diet model, should be weighed against the low content of phytates and the low content of sodium chloride, as well as the high amount of net base yielding vegetables and fruits. Increasing number of evidences supports the view that intake of high glycemic foods and insulinotropic dairy products is involved in the pathogenesis and progression of acne vulgaris in Western countries. In this context, diets that mimic the nutritional characteristics of diets found in hunter-gatherers and other non-western populations may have therapeutic value in treating acne vulgaris. Additionally, more studies is needed to determine the impact of gliadin, specific lectins and saponins on intestinal permeability and the pathogenesis of autoimmune diseases."

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