Environmental Medicine: Exploring the Pollutome for Solutions to Chronic Diseases.

Environmental toxicant exposure, according to many researchers in the field, is the leading cause of chronic disease and premature death globally. For the purposes of this review, we will use obesity and type 2 diabetes as examples of toxicant-induced chronic diseases. Endocrine Disrupting chemicals (EDCs) such as phthalates and bisphenols, per- and polyfluoroalkyl substances (PFAS), and persistent organic pollutants (POPs) have been linked to increased risk for obesity and type 2 diabetes in both animal and large epidemiologic studies. These two conditions are well-documented examples of evidence for mechanisms of both adipose metabolism disruption and pancreatic cell dysfunction. The implications for health care directives to both identify, prevent, and treat these exposures are reviewed.

Gastroesophageal reflux disease (GERD): a review of conventional and alternative treatments.

Gastroesophageal reflux disorder (GERD), a common disorder in the Western world, can lead to complications that include esophageal stricture and esophageal adenocarcinoma. Multiple challenges are associated with GERD treatment. First, lack of symptoms does not correlate with the absence of or the healing of esophageal lesions. Second, proton pump inhibitors, the current standard of care for GERD, are ineffective for the majority of GERD patients who have non-erosive disease. This article discusses these challenges, investigates the mechanisms of damage in GERD, and explores the existing data on unconventional forms of treatment, including melatonin, acupuncture, botanicals, and dietary interventions.

Thyroid disruption: mechanism and clinical implications in human health.

Exposure to specific environmental toxins, including polychlorinated biphenyls, dioxins, phthalates, polybrominated diphenyl ethers (PBDEs), and other halogenated organochlorines, has been shown to interfere with the production, transportation, and metabolism of thyroid hormones by a variety of mechanisms. A broad range of chemicals, with structural similarity to thyroid hormone, have been shown to bind to thyroid receptors with both agonist and antagonist effects on thyroid hormone signaling. The incidence of thyroid disease in the United States, particularly for thyroid cancer and thyroid autoimmune disease, is increasing substantially. The evidence for the significant effects of background levels of thyroid-disrupting chemicals, the known pathways for thyroid disruptors, and the evidence and implications for neurodevelopmental damage due to thyroid-disrupting chemicals is reviewed.

Iodine: deficiency and therapeutic considerations.

Iodine deficiency is generally recognized as the most commonly preventable cause of mental retardation and the most common cause of endocrinopathy (goiter and primary hypothyroidism). Iodine deficiency becomes particularly critical in pregnancy due to the consequences for neurological damage during fetal development as well as during lactation. The safety of therapeutic doses of iodine above the established safe upper limit of 1 mg is evident in the lack of toxicity in the Japanese population that consumes 25 times the median intake of iodine consumption in the United States. Japan's population suffers no demonstrable increased incidence of autoimmune thyroiditis or hypothyroidism. Studies using 3.0- to 6.0-mg doses to effectively treat fibrocystic breast disease may reveal an important role for iodine in maintaining normal breast tissue architecture and function. Iodine may also have important antioxidant functions in breast tissue and other tissues that concentrate iodine via the sodium iodide symporter.

Restless legs syndrome: pathophysiology and the role of iron and folate.

Restless Legs Syndrome (RLS) is a common movement disorder characterized by a circadian variation in symptoms involving an urge to move the limbs, usually the legs. Pregnant women, patients with end-stage renal disease or iron-deficiency anemia, and children with attention deficit hyperactivity disorder (AD/HD) have a significantly higher prevalence of RLS. The classic presentation includes the onset or worsening of symptoms when at rest and the circadian pattern of exacerbation of symptoms at night. These symptoms reflect a circadian fluctuation of dopamine in the substantia nigra. Patients with RLS have lower levels of dopamine in the substantia nigra and respond to iron administration. Iron, as a cofactor in dopamine production, plays a central role in the etiology of RLS. Folic acid administration has also been shown to alleviate the symptoms of RLS and may play a role in the treatment of primary (familial) RLS.

Lead toxicity part II: the role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity.

Lead is an environmentally persistent toxin that causes neurological, hematological, gastrointestinal, reproductive, circulatory, and immunological pathologies. The propensity for lead to catalyze oxidative reactions and generate reactive oxygen species has been demonstrated in multiple studies. These reactive oxygen species (ROS) inhibit the production of sulfhydryl antioxidants, inhibit enzyme reactions impairing heme production, cause inflammation in vascular endothelial cells, damage nucleic acids and inhibit DNA repair, and initiate lipid peroxidation in cellular membranes. These wide-ranging effects of ROS generation have been postulated to be major contributors to lead-exposure related disease. Antioxidants - vitamins B6, C and E, zinc, taurine, N-acetylcysteine, and alpha-lipoic acid, either alone or in conjunction with standard pharmaceutical chelating agents - have been studied in lead-exposed animals. The evidence for their use in lead exposure, alone and in conjunction with chelating agents, is reviewed in this article.

Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment.

The phasing out of leaded gasoline for transportation vehicles between 1973 and 1995 and the removal of lead from paint by federal mandate by 1978 have resulted in substantial lowering of mean blood lead levels in all segments of the U.S. population. However, because lead is a persistent metal, it is still present in the environment - in water, brass plumbing fixtures, soil, dust, and imported products manufactured with lead. Diagnosis of lead toxicity has traditionally been based on significantly elevated blood lead levels. However, data now implicates low-level exposures and blood lead levels previously considered normal as causative factors in cognitive dysfunction, neurobehavioral disorders, neurological damage, hypertension, and renal impairment. Chelation is the conventional recommendation in the case of blood levels associated with acute toxicity and encephalopathic damage. Issues surrounding the assessment of body lead burden and the consequences of low-level environmental exposure are critical in the treatment of chronic disease related to lead toxicity.

Selenium biochemistry and cancer: a review of the literature.

In recent years, the role of selenium in the prevention of a number of degenerative conditions including cancer, inflammatory diseases, thyroid function, cardiovascular disease, neurological diseases, aging, infertility, and infections, has been established by laboratory experiments, clinical trials, and epidemiological data. Most of the effects in these conditions are related to the function of selenium in antioxidant enzyme systems. Replenishing selenium in deficiency conditions appears to have immune-stimulating effects, particularly in patients undergoing chemotherapy. However, increasing the levels of selenoprotein antioxidant enzymes (glutathione peroxidase, thioredoxin reductase, etc.) appears to be only one of many ways in which selenium-based metabolites contribute to normal cellular growth and function. Animal data, epidemiological data, and intervention trials have shown a clear role for selenium compounds in both prevention of specific cancers and antitumorigenic effects in post-initiation phases of cancer.

Toxic metals and antioxidants: Part II. The role of antioxidants in arsenic and cadmium toxicity.

Exposure to toxic metals has become an increasingly recognized source of illness worldwide. Both cadmium and arsenic are ubiquitous in the environment, and exposure through food and water as well as occupational sources can contribute to a well-defined spectrum of disease. The symptom picture of arsenic toxicity is characterized by dermal lesions, anemia, and an increased risk for cardiovascular disease, diabetes, and liver damage. Cadmium has a significant effect on renal function, and as a result alters bone metabolism, leading to osteoporosis and osteomalacia. Cadmium-induced genotoxicity also increases risk for several cancers. The mechanisms of arsenic- and cadmium-induced damage include the production of free radicals that alter mitochondrial activity and genetic information. The metabolism and excretion of these heavy metals depend on the presence of antioxidants and thiols that aid arsenic methylation and both arsenic and cadmium metallothionein-binding. S-adenosylmethionine, lipoic acid, glutathione, selenium, zinc, N-acetylcysteine (NAC), methionine, cysteine, alpha-tocopherol, and ascorbic acid have specific roles in the mitigation of heavy metal toxicity. Several antioxidants including NAC, zinc, methionine, and cysteine, when used in conjunction with standard chelating agents, can improve the mobilization and excretion of arsenic and cadmium.

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

Mercury exposure is the second-most common cause of toxic metal poisoning. Public health concern over mercury exposure, due to contamination of fish with methylmercury and the elemental mercury content of dental amalgams, has long been a topic of political and medical debate. Although the toxicology of mercury is complex, there is evidence for antioxidant protection in the prevention of neurological and renal damage caused by mercury toxicity. Alpha-lipoic acid, a coenzyme of pyruvate and alpha-ketoglutarate dehydrogenase, has been used in Germany as an antioxidant and approved treatment for diabetic polyneuropathy for 40 years. Research has attempted to identify the role of antioxidants, glutathione and alpha-lipoic acid specifically, in both mitigation of heavy metal toxicity and direct chelation of heavy metals. This review of the literature will assess the role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

Nonalcoholic fatty liver disease: relationship to insulin sensitivity and oxidative stress. Treatment approaches using vitamin E, magnesium, and betaine.

Nonalcoholic steatotic hepatitis (NASH), the most prevalent form of progressive liver disease in the United States, is considered to be a manifestation of insulin resistance syndrome. There is increasing evidence that steatosis in NASH is a result of the pathology in fat metabolism occurring in obesity and insulin resistance. For steatosis to progress to necroinflammation and fibrosis, however, the theory of mitochondrial oxidative-stress induced cellular damage is receiving wide acceptance. Treatment approaches that address these etiologies are reviewed: betaine, magnesium, and vitamin E.

Eating disorders: a review of the literature with emphasis on medical complications and clinical nutrition.

Eating disorders, including anorexia nervosa, bulimia nervosa, binge-eating disorder, and atypical eating disorder (eating disorder not otherwise specified or NOS), are estimated to occur in 5-10 million young and adult women and one million males in the United States. The etiology of eating disorders is complex and appears to include predisposing genetic factors and serotonin dysregulation, as well as psychological factors that include a history of trauma and childhood sexual abuse. Both anorexia nervosa and bulimia nervosa are medical conditions complicated by multiple neuroendocrine dysfunctions, nutritional deficiencies, and psychiatric diagnoses. Medical complications, specific nutritional deficiencies, and research involving the therapeutic use of inositol and zinc are reviewed.