Thoughts on Non-Alcoholic Fatty Liver Disease and Chronic Disease.

The relentlessly increasing prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) represents yet another chronic disease epidemic. Why have so many chronic diseases become so common? This editorial discusses NAFLD in the context of a few of the factors that underlie so much of chronic disease: excessive fructose consumption; sedentary lifestyle; poor diet; body load of bisphenols, phthalates, per-/polyfluorinated substances, and polychlorobiphenyls; and several commonly prescribed drugs.

Subclinical Hypercortisolism: An Important, Unrecognized Dysfunction.

While Cushing syndrome is rare, but well-recognized, subclinical hypercortisolism (defined as excessive cortisol secretion without the classic manifestations of Cushing syndrome) is significantly more common. Subclinical hypercortisolism contributes to several chronic diseases, such as diabetes, osteoporosis, sarcopenia and hypertension. The incidence increases with age and correlates with body load of environmental toxins such as bisphenol A (BPA). This editorial discusses prevalence, contribution to disease, causes, diagnosis, and intervention.

Vitamin D (Like Every Nutrient) is a Team Player.

Vitamin D is critical for many physiological functions in humans. Numerous population-wide assessments have shown that vitamin D deficiency is very common. Unfortunately, far too many studies intending to assess the clinical efficacy of supplementation are poorly designed. They look at vitamin D as an isolated agent, independent of the complex matrix required for it to be physiologically effective and at dosages inadequate for much of the population. These errors cause inappropriate and invalid results that are then misused to not only recommend against supplementation but to also recommend against even measuring vitamin D levels. This editorial addresses the weaknesses of typical vitamin D research, such as VITAL, and the key factors that must be addressed for accurate vitamin D research.

Commonly Prescribed and Over-the-Counter Drugs as Secondary Causes of Osteoporosis-Part One.

Prescription and over-the-counter drugs have been effectively used to manage many diseases and to provide symptom relief. Unfortunately, their use may also result in adverse drug reactions and unintended consequences. Proper use of these powerful agents requires understanding both their desired effects and their potential downsides. Fully understanding the unintended consequences can be challenging. Virtually all safety studies are carried out for far shorter periods of time than the actual use of these agents in the real world. Some may take years of use before their sequelae are recognized. This is especially a problem where bone health is concerned since the damage caused by years of minor disruption in function does not show up until compounded by other factors, such as andropause and menopause. This 2-part editorial covers the primary classes of drugs that require bone health monitoring and that may require alternative prescriptions or mitigation strategies. Part One covers aromatase inhibitors, gonadotropin-releasing hormone agonists, anticonvulsants, benzodiazepines, antidepressants, insulin sensitizers, and NSAIDs and acetaminophen. Part Two covers opioids, glucocorticoids, calcineurin inhibitors, H2 blockers, diuretics, anticoagulants, thyroid medications, and contraceptives.

Commonly Prescribed and Over-the-Counter Drugs as Secondary Causes of Osteoporosis-Part Two.

In this second of a 2-part editorial, we continue our discussion of the importance of being aware that some clinically important prescription drugs can impair bone metabolism. While obviously most critical for women (and men) with osteopenia or osteoporosis, the guidance here is directly relevant to all patients as many are already experiencing decreased bone regeneration even if not severe enough for a formal diagnosis. Part One covered aromatase inhibitors, gonadotropin-releasing hormone agonists, anticonvulsants, benzodiazepines, antidepressants, insulin sensitizers, and NSAIDs and acetaminophen. Part Two covers opioids, glucocorticoids, calcineurin inhibitors, gastric acid blockers, diuretics, anti-coagulants, thyroid hormone medications, and contraceptives.

Environmental Toxins Are a Major Cause of Bone Loss.

The environmental metals cadmium, lead, and mercury, and chemicals such as pesticides, phthalates, and bisphenols, disrupt bone metabolism in many ways. Body levels of these toxins directly correlate, in a dose-dependent manner, with risk of fracture and osteoporosis. This editorial provides a brief summary of key research showing mechanisms of damage, sources, and key strategies to decrease body load.

Bariatric Surgery: Bad to the Bone, Part 2.

As discussed in Part 1, obesity is now a global epidemic affecting a significant and rapidly increasing number of adults, adolescents, and children. As the incidence of obesity has increased, so has the use of bariatric surgery to treat it. A growing number of recently published studies have reported that, despite calcium and vitamin D supplementation, the most frequently performed types of bariatric surgery, the Roux-en-Y gastric bypass (RYGB) and the sleeve gastrectomy (SG), cause significant, ongoing bone loss. Recent studies investigating nutrient malabsorption and changes in a wide range of hormones that are induced by bariatric surgery have indicated that calcium malabsorption is just the tip of a formidable iceberg. Part 1 reviewed the latest research findings confirming that the prevalence of obesity is, in fact, skyrocketing and that bariatric surgery causes ongoing accelerated bone loss. Part 1 also discussed the mechanisms through which the malabsorption of key nutrients induced by bariatric surgery adversely affects bone. The current article, Part 2, reviews the specific changes seen in bone metabolism after bariatric surgery and the current data on the underlying mechanisms, in addition to nutrient malabsorption, that may contribute to bariatric surgery-induced bone loss. These mechanisms include mechanical unloading, calcium malabsorption despite maintenance of vitamin D levels of ≥30 ng/mL, and changes in a number of hormones, including leptin, adiponectin, testosterone, estradiol, serotonin, ghrelin, glucagon-like peptide 1 (GLP-1), and gastric inhibitory peptide (GIP). Research discussing the use of nutritional supplements to help ameliorate bariatric surgery-induced bone loss is summarized. The adverse effects of bariatric surgery on bone must be widely recognized, and protocols must be developed to prevent early onset osteoporosis in recipients of this increasingly utilized and otherwise potentially life-saving surgery.

Bariatric Surgery: Bad to the Bone, Part 1.

Obesity is now a global epidemic affecting a significant and rapidly increasing number of adults, adolescents, and children. As the incidence of obesity has increased, so has the use of bariatric surgery as a medical solution. A growing number of studies now report that, despite calcium and vitamin D supplementation, the most frequently performed types of bariatric surgery, the Roux-en-Y gastric bypass and the sleeve gastrectomy, cause significant ongoing bone loss. In resources available to the general public and to physicians, this adverse outcome is rarely mentioned or is attributed solely to reduced calcium absorption. Recent studies investigating micronutrient malabsorption and changes in a wide range of hormones induced by bariatric surgery now indicate that calcium malabsorption is the tip of a formidable iceberg. The current article, part 1 of a 2-part series, reviews the latest research findings confirming that obesity prevalence is skyrocketing and that bariatric surgery causes ongoing, accelerated bone loss. Part 1 also discusses the mechanisms through which the bariatric surgery-induced malabsorption of key nutrients adversely affects bone homeostasis. Part 2 discusses the specific changes seen in bone metabolism after bariatric surgery and reviews current data on the underlying mechanisms, in addition to nutrient malabsorption, which are thought to contribute to bariatric surgery-induced ongoing accelerated bone loss. These processes include mechanical unloading and changes in a wide variety of hormones (eg, leptin, adiponectin, testosterone, estradiol, serotonin, ghrelin, glucagon-like peptide 1, and gastric inhibitory peptide). Also, part 2 covers interventions that may help lessen bariatric surgery-induced bone loss, which are now beginning to appear in the medical literature. Bariatric surgery's adverse effects on bone must be widely recognized and protocols developed to prevent early onset osteoporosis in the recipients of an increasingly utilized and otherwise potentially life-saving surgery.

Nothing Boring About Boron.

The trace mineral boron is a micronutrient with diverse and vitally important roles in metabolism that render it necessary for plant, animal, and human health, and as recent research suggests, possibly for the evolution of life on Earth. As the current article shows, boron has been proven to be an important trace mineral because it (1) is essential for the growth and maintenance of bone; (2) greatly improves wound healing; (3) beneficially impacts the body's use of estrogen, testosterone, and vitamin D; (4) boosts magnesium absorption; (5) reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α); (6) raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase; (7) protects against pesticide-induced oxidative stress and heavy-metal toxicity; (8) improves the brains electrical activity, cognitive performance, and short-term memory for elders; (9) influences the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD(+)); (10) has demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin's lymphoma; and (11) may help ameliorate the adverse effects of traditional chemotherapeutic agents. In none of the numerous studies conducted to date, however, do boron's beneficial effects appear at intakes > 3 mg/d. No estimated average requirements (EARs) or dietary reference intakes (DRIs) have been set for boron-only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y. The absence of studies showing harm in conjunction with the substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables or who is at risk for or has osteopenia; osteoporosis; osteoarthritis (OA); or breast, prostate, or lung cancer.

Canaries in the Phosphate-Toxicity Coal Mines.

Phosphorus is an essential mineral for cell structure and function but, when consumed in excess of the body's requirements, has many adverse effects on metabolism and health. Recently published research has revealed that the average American consumes far more phosphorus than the recommended dietary allowance (RDA) (700 mg/d for adults). Some individuals' daily phosphorus intake exceeds even an adult's tolerable upper limit (4000 mg/d). Until now, understanding of the adverse effects caused by high phosphorus intake has come from patients with chronic kidney disease (CKD), in whom high levels of serum phosphates are strongly associated with increased cardiovascular and all-cause mortality. Due to their impaired renal function, CKD patients cannot clear excess phosphorus, for which reason they must avoid processed foods, virtually all of which are laden with phosphate-containing food additives. Recently, it has become apparent that CKD patients are our canaries in the phosphate-toxicity coal mines. Excessive phosphorus consumption has now been shown to be clearly associated with cardiovascular disease, osteoporosis, and all-cause mortality in the general, healthy population.