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The list of endocrine disruptive chemicals (EDCs) stands at about 1000. Many EDCs have been identified as obesogens and that list is growing steadily as new compounds are added.⁵ Table 1 offers some examples of classes of chemicals and common exposure routes.

Table 1. Endocrine-Disruptive Chemicals

Chemical	Common Exposures
Organotin TBT	Seafood, polyvinyl chloride plastics, house dust
Nicotine	Fetal exposure from maternal smoking in pregnancy,  children with passive smoke exposure
Perfluorinated chemicals	Seafood, house dust, contaminated water near industry
Phthalates	Cosmetics, body care products, plastic containers, dust, fatty foods
Bisphenol A, S and F	Food and drink packaging, receipts, breast milk and formula
Acrylamide	Produced when cooking carbohydrate-containing foods at high temperatures by frying, baking, or roasting
Food additives & preservatives: MSG, 3-BHA (common preservative), dietary emulsifiers carboxymethylcelluclose and P-80, the surfactants DOSS and Span-80	Processed foods
Glyphosate	Commercial foods
DDT	Fatty animal products, including meat and dairy
PCBs	Fatty animal products, including meat and dairy
Organophosphate pesticides	Commercial foods, contaminated water, dust
Arsenic	Water, cigarette smoke, CCA-preserved wood structures, arsenic containing pesticides, contaminated foods
Cadmium	Cigarette smoke, contaminated foods, plastics, paints, batteries

Sleep

Sleep restriction and circadian rhythm disruption are both contributors to altered eating patterns and weight gain. Persistent short sleep patterns, measured as less than seven hours per night, predisposes adolescents and young adults to the development of obesity and increased waist circumference.⁶ Assessment of the National Health and Nutrition Examination Survey (NHANES), with a sample size of nearly 14,000 adults over the age of 20, demonstrated a linear relationship of increased BMI and waist circumference in those who slept fewer hours. Not only were adults who slept the recommended 7-9 hours more fit, those who slept more than 9 hours had improved anthropomorphic measurements over those sleeping the recommended 7-9 hours per night.⁷

The suprachiasmatic nucleus (SCN) in the hypothalamus, referred to as the central clock, is the primary mechanism for synchronizing circadian rhythms. The SCN itself is controlled by zeitgebers, environmental and social cues including daylight, artificial light, mealtimes, and timing of exercise/activity. Light-dark cycles have the greatest impact on the SCN, which blocks melatonin production when light is present and stimulates the pineal gland to secrete melatonin when it is dark. Melatonin, in turn, induces sleep, has antioxidant capacity, modulates the SCN, and improves insulin sensitivity. Because all the zeitgebers are controlled by lifestyle choices, this is a promising area of intervention for people with metabolic disease.⁸

There is an epidemiologic association of diabetes in people who work at night. This phenomenon is hypothesized to occur due to a misalignment between sleep/wake behavioral patterns and internal circadian rhythms, which are governed by daily light/dark sequence and the feeding/fasting cycle. Regardless of when a person sleeps, comparing normal night sleeping to daytime sleep of shift workers, there remains a consistent decrease by as much as 17% in glucose tolerance at 8 PM as compared to 8 AM. This is associated with insulin resistance that is commonly seen in those who work at night.⁹

Exercise

It has long been recognized that metabolism is modified by physical activity (PA). PA consists of structured exercise, sports, and activities of daily living, including occupation, leisure, and active transport. Metabolic impacts of PA include increased insulin sensitivity and insulin activity, with a reduction of insulin resistance, improved lipid profile, decrease in both fasting blood glucose and hemoglobin-A1C, and weight reduction, specifically visceral adipose tissue.¹⁰

While the light/dark cycle is the prime zeitgeber, exercise has been recognized as a secondary zeitgeber that can be used to entrain a health-promoting circadian rhythm. In shift workers and those who frequently change time-zones with travel, exercise has been effectively used to more rapidly re-establish healthy rhythms.¹¹

There is currently significant interest in discovering the best time for exercise. While exercise performance as measured by strength, endurance, and power is more robust in the late afternoon and evening, this does not answer the question of what time of day offers the most optimal health promotion. Studies in mice, muscle cells, and humans confirm this diurnal pattern of enhanced evening performance and illustrate the greater dependance on carbohydrates to produce this exercise efficiency.¹² This phenomenon has been successfully utilized by athletes to optimize their performance and set personal athletic records. For metabolically inflexible people, evening exercise may be a successful strategy to lower blood glucose after the evening meal. Conversely, morning exercise may better enhance fat oxidation. 

Exercise at 7 AM compared to both 1 PM and 7 PM in 20 prehypertensive men demonstrated improved blood pressure readings. Additionally, deep sleep and overall quality of sleep as measured by the number and duration of nocturnal wakening was significantly better in the early exercisers.¹³

Timing of exercise in relationship to a meal also has great impact. Pre-meal exercise significantly reduces appetite and food consumption. Research points to exercise-induced suppression of ghrelin, the hormone responsible for increasing appetite and adiposity. Of note, these effects are transient and demonstrate best efficacy when a meal is eaten within 30 minutes of exercise. Pre-meal exercise was also more effective than post-meal exercise at optimizing triglycerides and HDL cholesterol. This effect was longer lasting with effectiveness seen for many hours post exercise. Both pre- and post-meal exercise was effective for prevention of post-prandial hyperglycemia.¹⁴

Timing of Meals

While it is evident that energy expenditure must match caloric intake to avoid weight gain, less is said about the effects of the timing of a meal on metabolism. Triglycerides (TG) are higher and remain in the blood stream longer when a high-fat meal is consumed at night as compared to a meal eaten during the day. Comparing lunch to breakfast demonstrates that a mid-day meal produces the lowest blood TG levels whether or not a meal has been eaten at breakfast. This difference is hypothesized to reflect a greater uptake of TG into skeletal muscles cells mid-day. Glucose tolerance on the other hand is best in the morning, and carbohydrates are least tolerated in the evening. Amino acid absorption also shows a diurnal pattern with enhanced morning uptake as compared to the evening. Finally, the mismatch of the sleep/wake and feeding/fasting where calorie consumption is stacked in the evening, leads to metabolic disease and weight gain despite a eucaloric diet eaten that day.¹⁵

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