The Epidemic of Obesity, Diabetes and "Metabolic Syndrome:" Cell Energy Adaptations in a Toxic World?

"Metabolic syndrome" (MetSyn) has been termed the "Epidemic of the 21st century." MetSyn is an accretion of symptoms, including high body mass index (weight-for-height), high blood sugar, high blood pressure (BP), high blood triglycerides, high waist circumference (central/visceral fat deposition), and/or reduced HDL-cholesterol, the so-called "good" cholesterol. Epidemics of Obesity and diabetes are intertwined with, and accompany, the meteoric rise in MetSyn.

The prevalent view is that MetSyn is due to a glut of food calories ("energy") consumed, and a dearth of exercise energy expended, spurring weight gain—an "energy surfeit"—with the other features arising in consequence. After all, we have more access to calories, and are more often sedentary, than in times gone by. In turn, MetSyn factors are each linked, in otherwise-healthy young populations, to higher mortality.

But this normative view leaves many questions unanswered: Why do elements of MetSyn correlate? Why are overweight people today more likely to have diabetes than hitherto? Why are elements of MetSyn now emerging in infancy? Why is MetSyn materializing in poor and third-world nations?

The customary "explanation" also creates paradoxes. If MetSyn stems from energy surfeit, why do factors that reduce energy supply, or increase demand promote MetSyn—far from protecting against it?

· Sleep apnea (It’s a stronger MetSyn risk factor than overweight, though oxygen is the primary energy substrate; moreover sleep apnea treatment benefits each MetSyn element)

· Ultra low-calorie or low-fat diets

· Fasting, skipped meals

· Hypoglycemia-promoting diets (high-carbohydrate/low-fat/low-protein diets lead to unopposed insulin surge)

· Deficient sleep (more energy-expending wake time

· Illness/injury/surgery (high energy demand)

· Cold weather (mandating energy expenditure for thermogenesis)

· Nutrient and antioxidant deficiencies (adequacy required for energy production)

· Oxidative stressor exposure (impairs function of mitochondria, the energy producing elements of cells)

· Mitochondrial pathology.

Why do factors that protect from energy-deficit, reduce MetSyn factors—antioxidant cocoa and cinnamon, mitochondria-supportive coenzymeQ10—and exercise, which expends energy during activity, but boosts energy production throughout the day/night, via antioxidant effects, mitochondrial biogenesis, enhanced circulation and cardiopulmonary function—improving oxygen intake, delivery, and conversion to energy.

Why does MetSyn cease to elevate mortality (indeed, sometimes boosts survival) when the group studied has advanced age, heart failure, or severe kidney disease—conditions that all impair cell energy?

Suppose the correct explanation were the complete opposite to the accepted one? Could the features of MetSyn be the adaptive response to inadequate energy? After all, fat depots, glucose, and triglycerides are each accessory energy sources (oxygen is primary), blood pressure is needed to deliver these to tissues, especially when underperfused. Cell energy, central to cell and organism survival, is needed—continuously (we live only minutes without oxygen). The stretch is not so great: populations in which prior generations were energy starved have increased obesity/MetSyn now ("thrifty gene" thesis); and low energy supplyin utero is understood to foster MetSyn in adulthood.

This explains—as the energy surfeit view does not—why MetSyn exists at all: why elevated glucose, triglycerides, blood pressure (carrying oxygen, glucose, nutrients) and abdominal fat deposition cohere statistically. It explains why other energy supportive adaptations accompany them, like free fatty acids—as well as (metabolically active) ectopic fat: fatty-liver, fatty-pancreas, fatty-kidney—even fatty-streaks in the blood vessels; why MetSyn is linked to fatigue, and increased sleep duration (to conserve energy). Indeed, increased calories eaten, and reduced exercise expended—the usual MetSyn explanation—arise, too, as fellow energetic adaptations: Thus, this view is arguably not antithetical to the canonical one, but in one sense subsumes it. It explains, as the energy surfeit view does not, the populations at risk for MetSyn such as elderly (mitochondrial function declines exponentially with age) and those afflicted with sleep apnea—or any cause for recurrent energy production impairment. And it explains why in studies focused on persons with conditions that blight energy, those with MetSyn features "paradoxically" don’t do worse, or even fare better.

Why, then, is MetSyn an epidemic? Numerous energy-adverse secular shifts include nutrient-poor/low-antioxidant/high-prooxidant pseudofoods (nutrients are needed for energy production machinery, antioxidants protect from oxidative stress—for which the chief target is mitochondria, the energy producing bits of cells), decline of regular balanced meals, hypoglycemic-promoting macronutrient composition (simple carbohydrates without fat or protein engender unopposed insulin surges: glucose drops). But a central factor is the explosion of oxidative stressors in our environment which disrupt function of (and DNA in) mitochondria, cells’ energy-producers, E.g.:

· Metals and heavy metals (mercury in fish, high fructose corn syrup, broken light bulbs; arsenic to promote poultry growth; aluminum vaccine adjuvants—with proliferating childhood vaccinations)

· Plastics with bisphenol A

· Personal care products (chemicals in sunscreens, lotions, hairdyes, cosmetics, detergents, fabric softeners/dryer sheets, conditioners)

· Cleaning products

· Furnishings/clothes with formaldehyde (pressboard, no-iron cotton)

· Petrochemicals, combustion products

· Electromagnetic fields (electronics, cellphones, smart-meters)

· Fire retardants (pajamas, bedding)

· Dry-cleaning chemicals

· Air "fresheners"

· Pesticides, herbicides (potent oxidative stressors, now routinely applied at homes, recreational-sites, professional buildings)

· Termite tenting

· Prescription and OTC drugs including antibiotics—with exposure directly and through our food supply

· Antimicrobial soaps bearing active ingredients largely unfilterable from the water supply

· Air and water pollutants/contaminants

· Artificial ingredients in foods—transfats, artificial-sweeteners, dyes, preservatives.

The energy deficit ("starving cell") hypothesis accounts for scores of facts where the prevailing view provides no insight. Numerous observations deemed "paradoxical" in the standard view emerge seamlessly. It has testable predictions, e.g.: Multiple other oxidative stress- and mitochondrial disruption-inducing exposures that have not yet been assessed will promote one or multiple elements of MetSyn. For factors that relate at both extremes to MetSyn—e.g. short and long sleep duration—the energy disruptive one will prove to cause MetS, and the energy supportive one to serve as a fellow adaptive consequence.

This reframing addresses a pivotally important problem—some think MetSyn is slated to reverse the gains we have made in longevity—with a perhaps surprising conclusion, that should precipitate a revision in our thinking about causes of MetSyn, and importantly, its solutions.