SPECIAL ISSUE ON WEIGHT LOSS, DAIRY
Nearly everyone has tried to lose weight. Often, we fail and/or regain the weight. Why? This issue features two full articles on this vexing problem. If you do not wish to study them, here is a brief summary on why it is difficult to lose weight: decrease in activity, hormonal issues created by dieting, microbiome (gut bacteria imbalances,) stress and an addiction to refined sugars. Overcoming these issues is not easy. Often, we need professional help. It is possible to maintain weight loss, but it takes constant vigilance, regular exercise and eating most calories early in the day.
The third article is on the controversy over dairy consumption. I hope you milk it for all its worth. Here is a brief summary: milk does not do a body good.
Best health to you, Hugo Rodier, MD
Unexpected Clues Emerge About Why Diets Fail
By Daniel Engber, J. Scientific American January 13, 2020
The physiology of weight regain still baffles scientists, but surprising insights have emerged.
“Why is it so hard to lose weight and keep it off? For a moment, several years ago, it looked like we had an answer. In May 2016, The New York Times ran a front-page story on the findings from a study out of the US National Institute of Diabetes and Digestive and Kidney Diseases: fourteen reality show contestants had been tracked for half a dozen years after appearing on the program The Biggest Loser. Through dieting and very intensive exercise, each had lost at least 50 pounds during their time on the television series—and a couple had shed more than 200—but the follow-up study found they’d regained about two-thirds of what they’d lost, on average. A handful ended up even heavier than when they first appeared on the television program.
This weight rebound came as no surprise. The tendency of dieters’ bodies to creep back toward prior weights has been among the most reliable and replicable results in the study of weight loss interventions. Research suggests that roughly 80%of people who shed a significant portion of their body fat will not maintain that degree of weight loss for 12 months; and, according to one meta-analysis of intervention studies, dieters regain, on average, more than half of what they lose within two years. Meanwhile, follow-up care that is meant to stave off this backsliding via behavioral or lifestyle interventions appears to be effective only at the margins: across several dozen randomized trials, the benefits of these programs—in terms of minimizing regain—were pretty small at two years, and undetectable thereafter. In short, we’ve known for quite some time that while it’s hard to lose weight, it’s even harder to keep it off.
The Biggest Loser study didn’t just recapitulate this disheartening rule of thumb, however. It appeared to offer something more—an explanation, of a sort, for why the weight rebound might be happening. When the researchers at the National Institute of Diabetes and Digestive Kidney Diseases, led by physiologist Kevin Hall, examined the contestants six years after the show ended, they noticed major changes to the rates at which their bodies were expending energy. The contestants’ resting metabolic rates had ended up much lower than expected, even taking stock of their smaller statures overall: most were burning at least 400 fewer calories than the researchers’ model had predicted. Some initial dip in metabolic rate is a known side effect of weight loss, but Hall and his colleagues didn’t realize that it would persist for so long, and to such a large extent.
“Dieters are at the mercy of their own bodies,” explained the write-up in the Times, in a lightbulb formulation that helped to make the story one of the newspaper’s top ten most read of the year (just a few slots south of ‘Donald Trump Is Elected President’). For many readers, or dieters, this would be a way to sop frustration with a dour fact of physiology—and find solace in the revelation that shedding weight provokes a natural reflex to regain.
The Biggest Loser study only gestured at the underlying scientific problem, though. Yes, dieters are at the mercy of their bodies, but their reflex to regain could be undergirded by a wide array of mechanisms, such as flagging satiety hormones, adaptations in the microbiome of the gut, and alterations to the makeup of their fat tissue. Changes to the metabolic rate may be thought of as one more factor on this list, as an outcome of a bunch of lower-level processes. In any case, the 2016 research, like other studies of this topic, has been nagged by a conundrum: how can you tell whether any single factor is in fact a cause of dieters regaining weight, as opposed to just a signal of their having gotten thinner in the first place?
That ambiguity shows up in the data from the reality show contestants. It’s true that almost all of the dieters’ resting metabolic rates had decreased across the follow-up, and that this change would have seemed to favor weight rebounds, all else being equal. But it also seems that their metabolic slowing was not the primary driving force of anyone’s weight regain. In fact, Hall and his colleagues found that contestants who showed up for testing six years later with the lowest metabolic rates were the same ones who actually had the most success in maintaining their weight loss. A lasting improvement to their exercise habits had allowed them to maintain a lower weight, and also apparently dampened their resting metabolic rates.
Hormonal heuristics
Ambiguities abound in the science of weight regain. One line of research, for example, looks at changes in circulating hormone levels in the aftermath of dieting. In a highly cited 2011 study published in the New England Journal of Medicine, Australian researchers put 50 overweight or obese people on a two-month diet of Optifast shakes and vegetables, yielding a total of about 500 calories per day. A year later, blood samples were collected from the patients for analysis of fasting and postprandial levels of ghrelin, leptin, peptide YY, amylin and other hormones.
The dieters had lost an average of 30 pounds during the initial intervention, and then gained back about a dozen pounds over the months that followed, when they were given advice on healthy nutrition and exercise habits, but were allowed to eat as they liked. Their endocrine markers showed a similar acute effect, followed by a partial rebound. Levels of the satiety-inducing hormone leptin, for example, initially dropped by almost two-thirds during weight loss when they were on the 500-calorie-per-day diet, but remained more than one-third reduced one year later, after all those months without dietary supervision. Similar patterns were seen for the other assays: across the board, it looked like dieting induced a rapid shift in hormone levels that would tend to favor increased appetite (and thus weight gain); and this effect would not return to baseline even after many months had passed.
Again, there was some murkiness regarding cause and effect. The study hinted that the drop in leptin levels, and other hormonal changes, might have been what spurred participants to gain back almost half of what they’d lost. But the hormonal changes could just as well have followed from the weight loss. Leptin levels in the plasma are known to drop during a very low-calorie diet, as well as when a person has been shedding fat. Contestants on The Biggest Loser, for example, saw their concentrations founder by almost 95 percent over the course of the weight-loss competition. That changes such as these might still be detectable, to some degree, 12 months down the road could just as well reflect the fact that the patients had maintained some degree of weight loss across that time, too.
That may be why follow-up attempts to predict the magnitude of a person’s weight regain from the depth to which his or her leptin levels drop have been largely unsuccessful. Kevin Hall wonders if the correlation between these two variables might even end up the reverse of what you might expect, as he’d found for resting energy expenditure. “If you’re the kind of person who can decrease your calorie intake and therefore lose a lot of weight,” he says, “then you’re going to experience the greatest decrease in leptin.” Furthermore, he speculates, if you’re the kind of person who is able to maintain that change in lifestyle, you’ll also be the kind of person whose leptin levels stay reduced.
Out of shape
A more comprehensive theory of weight regain, accounting for a broad array of mechanisms, may help address some of the confusion in this field. Researchers Marleen van Baak and Edwin Mariman of Maastricht University, for example, have proposed that the compensatory reflex begins with changes to the shape of fat cells. As these cells drain and shrink, their membranes pull away against the points of adhesion to the nearby extracellular matrix, creating mechanical stress. This in turn sets “a multitude of adaptations” in motion, they said in an interview, although the strength of these responses will differ across individuals.”
According to their preliminary model, which is based on both in vitro studies of adipocytes and examinations of protein expression during and after weight loss, the mechanical tension that shedding weight creates at the fat-cell membranes inhibits further fat release and primes those cells to be filled again. At the same time, they theorize caloric restriction may deprive adipose tissue of the energy it would need to relieve this stress through remodeling of the extracellular matrix. The stress response could also lead to changes in the adipocytes’ secretion of leptin and other signaling proteins, and persistent inflammation in the aftermath of someone losing weight.
The Maastricht group has been looking to support this theory with data from the “YoYo study”: a randomized controlled trial of around 60 participants who were placed on either an intense crash diet (of 500 calories per day over 5 weeks), or a slower one (of 1,250 calories per day over 12 weeks). This was followed by a brief weight-stabilization period (in which they received about as many calories as they would need to keep a constant weight) and then further check-ins for the next nine months. The team took biopsies of adipose tissue at the end of each study phase, measured changes to its gene activity, and checked to see which, if any, might be correlated with weight regain. In a subgroup analysis of the crash diet participants, 15 genes related to the extracellular matrix were identified, and 8 more associated with stress response.
Others are looking for answers in the genome. “At this point in time, people are still adding different pieces to the puzzle,” says Jeanne McCaffery of the University of Connecticut. Her own puzzle piece relates to the question of inherited genetic risk for weight regain: “We were excited about the hypothesis that if you were genetically disposed to have a higher body weight, you’d put on weight again more quickly,” she adds. But a genome-wide association study to determine whether genes that have been linked to the development of obesity might also be predictive of weight regain failed to turn up any positive results. That could be on account of its insufficient sample size, McCaffery explains. The study had about 3,000 people in the weight-loss condition, whereas similar studies of the genetics of obesity have been far larger in scope.
The one point on which nearly all researchers agree is that the physiology of weight regain, like the physiology of obesity itself, is almost certain to reflect a very complicated mix of factors ranging from genetics to behavior and the environment. That means we’re unlikely to find any magic-bullet method for keeping pounds from coming back. Indeed, some degree of rebound may be more or less inevitable for the majority of dieters.
But even that news may not be as bad as it seems. Just last year, a team of researchers at the University of Alabama at Birmingham, led by David Allison, put out a rodent study of a provocative idea: what if there were lasting benefits to losing weight—even when that weight is almost certain to be regained? The researchers randomized 552 obese, Black-6 mice into four groups: one set of animals ate a high-fat diet at will and remained obese; another two sets received either moderate or more extreme caloric restriction, and stabilized at a ‘normal’ or intermediate weight; and a fourth was put through several yo-yo cycles of restricted and ad libitum feed, losing weight and then gaining it right back.
At the end of the study, the mice that remained obese throughout the experiment had markedly increased mortality: they lived, on average, for just 21 months, as compared to the 26-month average lifespan of the mice that had been put on the most extreme diets and kept at a normal weight. More surprising was the fact that the yo-yo mice also gained longevity, by virtue of their weight cycling: they lived an average of 23 months, about the same as the mice that were kept under chronic, moderate calorie restriction.
In other words—at least for mice—it may be that weight regain doesn’t cancel out all the benefits of dieting. Those who feel they’re going around in circles may take some solace in this notion: even if your fat cells tug and twist your weight loss back to zero, that doesn’t mean that you’ve been pulled back to where you started.”
A Time to Eat and a Time to Exercise
Evelyn B. Parr; Leonie K. Heilbronn; John A. Hawley
J. Exerc Sport Sci Rev. 2020;48(1):4-10.
Abstract
This Perspective for Progress provides a synopsis for the potential of time-restricted eating (TRE) to rescue some of the deleterious effects on circadian biology induced by our modern-day lifestyle. We provide novel insights into the comparative and potential complementary effects of TRE and exercise training on metabolic health.
Introduction
Numerous metabolic and physiological processes are underpinned by 24-h biological oscillations that are under the control of a central circadian clock, present in all mammalian cells.[1] Synchronization of the expression of circadian clock genes in the suprachiasmatic nucleus (SCN) of the hypothalamus is primarily governed by the light-dark cycle.[1] However, other environmental and behavioral time cues, termed “zeitgebers,” such as the timing of meals and exercise, along with sleep-wake cycles, can “fine-tune” the central clock.[2] These nonphotic cues can reset or induce time-phase shifts in circadian oscillations through mechanisms independent of the SCN.[3,4] Indeed, our prevailing modern lifestyle (round-the-clock access to energy-dense food, low levels of habitual physical activity accompanied by periods of prolonged sitting, and inadequate quality/quantity of sleep) interacts with underlying biology to create an environment in which circadian rhythms are disrupted, often resulting in a plethora of metabolic conditions.[3–5] This was not always the case.
Throughout human evolution, lifestyle and energy availability were inextricably linked to the periodic cycles of feasts and famines. During these natural cycles, specific genes evolved to regulate efficient storage of endogenous fuel stores, so-called thrifty genes.[6] During the early hunter-gatherer period, there was also the selection of genes and traits to support a “physical activity cycle”,[7,8] and under these constraints, most of the present human genome evolved. Today, those alleles and traits that evolved for energy storage and locomotion are exposed to a host of unfavorable environment cues over an extended lifespan, perturbing the intrinsic circadian clock and increasing the risk of many lifestyle-induced metabolic diseases.[3–5] In this Perspective for Progress, we provide a synopsis of the efficacy of diet and exercise interventions to rescue many of the deleterious effects on circadian biology induced by our modern-day lifestyle. We describe new insights into the comparative and potential complementary effects of exercise training and a novel dietary intervention that encourages a longer daily duration of fasting to improve human metabolic health, but argue that exercise still remains the optimal strategy to improve the majority of lifestyle-induced disorders in metabolism.
Strategies to Improve Metabolic Health
The benefit of improving dietary quality combined with undertaking regular exercise is undoubtedly the best approach to prevent/treat noncommunicable diseases.[9] However, adherence to lifestyle modifications is poor, and such behavioral changes have met with limited success at the population level.[10] Consequently, diet and exercise strategies that focus on more socially acceptable and achievable interventions (e.g., exercise “breaks” after meals, changing the timing of eating, high-intensity sprint interval training) may be more effective for improving metabolic health.[11–13] The interactions between the timing of exercise and meals is complex: changes in energy and/or macronutrient intake rapidly alter the concentration of blood-borne substrates and hormones causing marked perturbations in the storage profile of skeletal muscle and other insulin-sensitive tissues.[14] In turn, the energy status of muscle exerts marked effects on resting fuel metabolism and patterns of fuel use during exercise,[15] influencing acute regulatory processes underlying gene expression and cell signaling.[16] Although it is generally accepted that adaptations to exercise training result from the cumulative and chronic effect of the transient increases in mRNA transcripts that encode for various proteins after each successive exercise bout,[17] the chronic effects of shifts in meal timing are, as yet, unknown.
Diet Interventions
In the past decade, evidence has accumulated to suggest that timing of meals affects a wide variety of physiological functions, including the sleep/wake cycle, core body temperature, athletic performance, and mental alertness.[2] Furthermore, the time of meals has a profound effect on skeletal muscle insulin sensitivity and whole-body metabolic health[18] and can be manipulated to help prevent/treat a number of lifestyle-related disease states. This has been termed “chrono-nutrition” and reflects a new appreciation that the timing of meals in addition to the energy content and macronutrient composition of food is critical for the well-being of an organism. Hence, chrono-nutrition refers to the synchronization of eating with the body’s entrained circadian rhythms.[2]
Numerous diet strategies have been proposed to curb the soaring prevalence of obesity and lifestyle-induced metabolic disorders. A feature common to most of these diets is the manipulation of the feeding-fasting cycle. In this regard, time-restricted eating (TRE), in which energy intake is limited to a “window” of less than 10 h·d−1, has emerged as a practical intervention to increase the length of time spent fasting, by reducing the time over which energy is consumed (Figure 1). Gill and Panda[11] were the first to show that 16 wk of TRE in overweight humans (body mass index (BMI), >25 kg·m−2) induced a modest weight loss (~3% body mass) after decreasing the eating window from more than 14 h to less than or equal to 10 h·d−1. This weight loss was maintained for 12 months, suggesting TRE may be a practical strategy for weight maintenance over the long term. Although the participants in that study[11] were not asked to change nutritional quality or quantity, reducing daily eating duration led to 20% reduction in energy intake.[11] With small subject numbers (five males and three females) and no control group, wider interpretation of the results of this study is limited.
Proposed perturbations to glucose, insulin, and free fatty acid (FFA) concentrations over a 24-h period with time-restricted eating (TRE) (orange, dashed lines) or “exercise snacks” (~10 min walking; green, dashed lines) compared with typical circulating metabolite patterns in response to three meals consumed during waking hours.
Other studies since that of Gill and Panda[11] confirm that TRE induces modest weight loss,[19–21] although these interventions have been short term (≤12 wk) with no follow-up. For example, Gabel et al.[21] reported that 23 individuals with obesity who adhered to 12 wk of TRE (1000–1800 h) for ~5–6 d·wk−1 had a loss of 2.6% body mass. Others have also observed small reductions in energy intake when implementing TRE of 8–10 h·d−1,[11,21,22] making it difficult to attribute weight loss solely to the timing of energy intake. Of note, energy-restricted dietary interventions, without an exercise stimulus, typically induce a loss of ~250–300 g of lean tissue for every kilogram of weight lost,[23] and although no measures of body composition have been made in any TRE study to date, such losses in lean mass would be expected to be similar to dietary fasting interventions.[24]
The results of a recent study suggest that the health benefits of TRE may be independent of weight loss.[25] In the first supervised trial of early TRE (eTRE), in which all meals were provided to participants, Sutton et al.[25] studied eight men with prediabetes who were randomized to eTRE (meals consumed within 6 h, last energy intake before 1500 h) or an unrestricted eating pattern (meals consumed over 12 h, from 0800 to 2000 h) for 5 wk. No measures of body composition or physical activity were assessed. Compared with unrestricted eating, eTRE improved insulin sensitivity and B-cell responsiveness, blood pressure, and oxidative stress, although selected measures of appetite were also modified.[25] The precise mechanism(s) of how TRE improves health outcomes without enforced energy restriction is currently unknown.
The circadian clock affects hormonal metabolism, with the timing of meals fine-tuning endocrine biology with regard to glycemic control.[26] An influx of glucose from cortisol-stimulated hepatic glucose production occurs around 0800 h, when cortisol levels typically peak after waking.[27] Delaying (not skipping) breakfast to late morning (~1000 h) and missing the circadian-related release in hepatic glucose[28] could improve postprandial glycemic control. Insulin secretion and sensitivity also are under circadian regulation: these parameters are increased early in the day and drop in the evening,[28] even when there are equidistant 12-h fasts between meals.[29] Thus, the reduction in insulin sensitivity in the evening explains the impaired glucose tolerance measured in response to late-night dinner consumption.[30,31]
An important question for both health outcomes and the practicality of implementing TRE interventions is whether the window of meal timing throughout the day, as well as the start/finish time of meals, is associated with the magnitude of improvement in health markers. The eTRE intervention by Sutton et al.[25] revealed hyperinsulinemia was reduced when daily eating was completed by 1500 h, but such a strict eating protocol is not likely to be practical or socially acceptable at a population level. Studies of “late” TRE, or when total energy intake was restricted to meals consumed after 1600 h, have resulted in impaired fasting glucose, lowered glucose tolerance, and increased ratings of hunger.[32,33] Studies that have commenced TRE in the middle of the day have shown either no effect[21] or tended to be beneficial with regard to glycemic control.[19,22] In the only comparative time window TRE study to date, Hutchison et al.[34] compared 1 wk of eTRE (0800–1700 h) with delayed TRE (1200–2100 h) in men at risk of developing type 2 diabetes (T2D). Both protocols improved glycemic control in response to a test meal, but only eTRE improved overnight fasting glucose levels.[34] Clearly, there is a trade-off between the feasibility of undertaking TRE and adherence to an optimal TRE window that aligns with healthy circadian rhythms. Accordingly, future studies should determine whether it is the placement of the eating window or the duration spent in the fasted state over each day that induces many of the improvements in metabolic health.
Satiety-inducing hormones glucagon-like peptide-1 (GLP-1), glucose-inhibitory peptide (GIP), and peptide YY (PYY) are increased, and the hunger-inducing hormone ghrelin is suppressed in response to meals. These gut hormones play a critical role in modulating appetite and the rate of gastric emptying (which slows in the evening), and, therefore, the glycemic response to meals. Secretion of these hormones is under circadian regulation.[35] For example, ghrelin release peaks at mid evening (~2000 h) and is lowest upon waking,[36] explaining, in part, the strong biological drive to eat at night. As such, diets that promote greater energy intake in the morning and lower energy intake (or longer fasting) in the evening are likely to produce sustained weight loss.[37,38] Perhaps surprisingly, subjective ratings of appetite are not increased by TRE, at least when measured during the day.[11,25] TRE initiated from 0800 to 1700 h or from 1200 to 2100 h did not alter the postprandial suppression of ghrelin or the rise in PYY, GLP-1, or GIP response, and there were no differences in subjective appetite ratings during a meal test.[34]
Reducing the time spent in a postprandial and postabsorptive state improves glycemia[39] while concomitantly shifting patterns of substrate use. Prolonged (>24 h) fasting increases the production of ketone bodies in humans[40] and rates of whole-body fat oxidation. Extended fasting periods are likely to upregulate fat oxidation via an increase in lipolysis and circulating free fatty acids (FFAs). Throughout a typical day of eating (i.e., three meals plus snacks), circulating FFA and triglyceride (TG) concentrations are suppressed,[41] and prolonged energy consumption (>14 h·d−1) limits lipolysis and rates of FFA oxidation at rest. An extended overnight fast with TRE augments the increases in FFAs and TGs, resulting in elevated fasting lipid profiles.[25] Whether such a lipid profile is beneficial for human health over the long term remains to be established. To date, the results from animal studies reveal that hepatic fat stores are reduced with TRE,[42] but further investigations in humans are needed to understand the effect of TRE on whole-body and hepatic lipid metabolism.
In terms of sustainability, TRE seems to offer a practical advantage over stricter energy-restricted diet interventions, given there is no specific instruction around energy restriction or discretionary food choices. However, the types of foods we consume often are aligned closely to distinct times of the day; alcohol typically is consumed at the end of the day, as are sweet (refined sugar) foods such as ice cream. A reduction in food intake later in the day may not only reduce total energy intake but also curtail discretionary food intake and improve overall dietary quality. However, it also is possible that placing time restrictions on eating could result in poorer food choices in some.
Exercise Interventions
TRE extends the length of time in the fasted state, inducing several responses that are similar to those observed after exercise training. However, when compared with dietary interventions, both the amplitude and extent of exercise training-induced responses/adaptations are likely to be greater in a head-to-head comparison. Evidence for such a premise comes from epidemiological data demonstrating that the association between low cardiometabolic fitness (i.e., maximum oxygen uptake) and all-cause mortality is stronger than that of obesity (i.e., high BMI).[46] Exercise training delays the onset of at least 40 chronic metabolic conditions/diseases (see[47,48] for reviews). However, getting people to comply with even the minimal recommended quantity and quality of exercise required to confer health benefits has proven difficult.[10]
Effects of time-restricted eating (TRE) and exercise training on metabolic health in humans. Green arrows, positive change; red arrows, negative change; question mark, unknown effect. SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.
Exercise training has a significant impact on body composition, reducing both subcutaneous and visceral fat[49] while preserving lean mass.[23] Aerobic-based exercise of sufficient duration/intensity promotes beneficial changes in whole-body metabolism and reduces fat mass,[50] whereas resistance exercise preserves or increases lean (muscle) mass.[51,52] Energy-restricted diets in isolation are effective short-term strategies for rapid weight loss but result in a reduction in both fat and muscle mass, predisposing one to an unfavorable body composition and poor health prognosis. Exercise typically results in only a modest increase in total daily energy expenditure but has minimal effects on long-term weight loss, depending on the volume/intensity of exercise performed.[23] As such, the performance of regular and appropriate exercise is the only mechanism to improve body composition (i.e., lose fat mass while maintaining lean mass). For an individual solely focused on changes in weight, the short-term reduction in body mass with TRE may initially exceed that from exercise, masking any long-term exercise-induced changes to body composition. Long-term studies of TRE that incorporate body composition measures are urgently needed to understand the effects induced by the longer duration of daily fasting.
Although TRE interventions have the potential to change habitual dietary practices, there may also be changes to physical activity patterns.[53,54] The effect of increasing the amount of exercise on dietary intake, however, appears equivocal; increases in physical activity have either had no effect[55,56] or resulted in an improvement[57] on dietary quality. In older adults with prediabetes, performing regular resistance-based exercise reduced self-reported intake of carbohydrate, sugar, sweets, and desserts, with little effect on protein intake.[58] Such changes to total energy and macronutrient intake may be related to changes in the regulation of appetite with exercise. Acute physical activity transiently represses appetite in both lean and obese individuals[59] via a suppression of ghrelin and increases in PYY and GLP-1.[60] However, the effects of longer-term exercise training on the control of appetite are equivocal.[61,62] Exercise training may balance appetite responses by an increased satiety response to a meal despite an increased drive to eat.[63,64] Exercise training also reduces circulating leptin concentrations, reducing fat mass, and positively affects appetite and body composition.[65,66] Therefore, exercise has the ability to reduce appetite and improve overall dietary intake. To date, there have been no interventions of TRE in combination with an exercise training program compared with TRE alone.
A single bout of exercise increases skeletal muscle glucose uptake.[67] However, this “insulin-sensitizing” effect is short-lived and dissipates after ~48 h.[68] In contrast, repeated physical activity (i.e., exercise training) results in a persistent increase in insulin action in skeletal muscle from health individuals and people with insulin resistance and obesity.[69] Exercise training also improves glucose tolerance.[70] The precise volume of exercise required to induce a clinically meaningful change in glycemia is a contentious issue, but small in relation to the time spent awake. Dempsey et al.[12,71] reported that less than 40 min of walking or body weight resistance exercises (12 × 3-min bouts undertaken between 0900 and 1500 h) improved both waking and nocturnal glucose concentrations in individuals with T2D. Breaking up exercise bouts (“exercise snacking”) into 3 × 10-min bouts after meals improved daily glycemic control in individuals with T2D to a greater magnitude than a continuous 30-min walk.[72] In individuals with prediabetes, three “exercise snacks” (6 × 1 min of high-intensity activity before each meal) improved daily glycemia on both the day of exercise and over the subsequent 24 h.[13] As such, adequate physical activity no matter how it is accumulated across a day is effective in attenuating postprandial glucose and insulin concentrations (Figure 1).
Regular exercise increases postexercise rates of whole-body fat oxidation and improves metabolic flexibility (the ability to respond to changes in hormonal milieu and switch between fuel sources in response to the prevailing metabolic demand)[73]). Exercise also has a positive effect on circulating lipid profiles, with decreased fasting and postprandial FFA concentrations, increased uptake of FFA by the muscle, and lower uptake of FFA to the liver.[74] contributing to improvement in nonalcoholic fatty liver disease.[75] A meta-analysis of aerobic-based exercise training programs performed for 12 wk or longer revealed reduced circulating TGs and higher high-density lipoprotein (HDL), low-density lipoprotein, and total cholesterol.[76] Reductions in cholesterol and circulating lipids have also been observed both in response to a single bout of resistance-based exercise[77] and after resistance training,[78] although the magnitude of reduction is typically less than that observed after aerobic exercise training. Even short bouts of physical activity accumulated for ~40 min across a day improve the postprandial handling of lipids.[79]
The optimal timing of exercise to maximize health benefits is currently unknown and likely to be confounded by a number of variables (health status of the individual, entrained waking time, circadian phenotype, mode and duration/intensity of exercise, and meal timing). Acute performance of aerobic-based exercise (i.e., continuous or high-intensity interval training) in the afternoon/evening improves glycemic control,[72,80] likely due to the timing in relation to both circadian-related insulin resistance and the postprandial state.[81] Resistance exercise performed in the morning, afternoon, or evening improves force generation (i.e., muscle strength).[82,83] However, there is no clear consensus regarding the merits of performing either morning or evening exercise with regard to superior improvements in aerobic capacity[84] or resistance training/strength adaptations.[85] Although it has recently been proposed that time of day is a major modifier of exercise responses/adaptations and associated metabolic pathways[86] and that there is a day-night rhythm in mRNA expression of molecular clock genes in human skeletal muscle,[87] we urge caution with regard to recommendations on the “optimal time of day” to exercise for optimal health benefits: individual health status (i.e., known cardiovascular disease/hypertension), personal exercise goals, and feasibility should all be considered.
TRE and Exercise Training: Some Considerations
The discovery of muscle “cross-talk” with other organs, including adipose tissue, liver, pancreas, bone, and the brain, provides a framework for understanding how exercise mediates many of its beneficial whole-body effects.[88] Although several acute responses to TRE are similar to those attained after exercise training (Figure 2), exercise evokes widespread and extensive remodeling of almost every organ/tissue in the body (i.e., increased bone mineral density, improved cardiovascular dynamics and blood flow, increases in muscle oxidative capacity and capillarization, increases in muscle cross-sectional area, etc.). Indeed, it is the very complexity and multiplicity of networks involved in exercise responses that make it unlikely that such whole-body effects could be induced by TRE.
Whether adding exercise training to a TRE regimen or supplementing an exercise program with TRE confers any additional benefits above and beyond either intervention in isolation has not been systematically investigated. To date, only two TRE interventions in humans have included exercise as an adjunct to changes to dietary timing.[19,89] Moro et al.[19] studied healthy males during 8 wk of resistance training who were assigned either to a group who undertook alternate days of late TRE (1300–2000 h) or to a group who were unrestricted in their eating (0800–2000 h) but matched for energy intake. Although both groups increased muscle mass after the intervention, only the TRE group decreased total body mass and fat mass, with small but concomitant positive improvements in several metabolic health markers (improved glucose, HDL, and TG profiles).[19] Tinsley et al.[89] examined the effects of 8 wk of resistance training (3 d·wk−1) with or without late TRE. The TRE protocol consisted of consuming all meals within a 4-h period between 1600 h and midnight on nontraining days (4 d·wk−1), with no limitations on quantities or types of foods chosen. A “control” condition consisted of resistance training with no restrictions on energy intake on the nonworkout days. Late TRE resulted in a 10% reduction in energy intake compared with the control group but did not confer any additional improvements in body composition, and markers of metabolic health were not measured.[89] Post hoc tests revealed a small positive effect of the resistance training on the accretion of lean tissue mass in the control group only, which was likely due to the greater (1.4 vs 1.0 g·kg−1 body mass) protein intake in the control compared with the TRE group. Thus, the additive effects of TRE to exercise training may be dependent on the effects that TRE has on both total daily energy and protein intake, and the timing of protein ingestion relative to when the exercise is performed.
In other interventions of TRE, participants have been instructed “not to change physical activity levels”[20,21,34] or there has been no control of physical activity.[11,22] There are no studies investigating the potential for an additive benefit of exercise training to a TRE dietary regimen compared with TRE alone. As dietary quality and quantity are not markedly improved when individuals undertake regular physical activity, complementing exercise training with TRE may help modify behavioral patterns of eating, (i.e., reduced end-of-day snacking/alcohol consumption) and enhance overall health benefits. For individuals with medical conditions where physical activity cannot be performed, TRE offers a feasible strategy to improve or maintain metabolic health. However, we propose that for most “healthy” individuals, adding TRE to a program of regular physical activity would impart minimal additive effects on a range of health-related outcomes.
Future Perspectives
Optimal cardiometabolic health for individuals at risk of chronic lifestyle-related diseases results from interventions in which dietary intake is reduced and/or quality is improved, and exercise of sufficient mode, duration, and intensity is performed.[23,90] However, adherence to changes in habitual dietary patterns is often considered more arduous than medical therapy,[91] and the majority of individuals report “a lack of time” as the major reason for not undertaking regular exercise.[92] As such, the debate becomes “what priority should be given to modifying diet versus implementing exercise training for improving health outcomes?” As energy, via food, is required to sustain life, it is perhaps no surprise that dietary modifications are often the first in line of attack in the arsenal of lifestyle interventions to prevent/treat many metabolic diseases. Although there is an extensive menu of dietary options available to improve metabolic health outcomes, their success/failure, as with any exercise intervention, depends on long-term adherence.[93] We believe that exercise training undertaken in accordance with national and international guidelines imparts greater whole-body and tissue-specific metabolic health benefits than any current dietary intervention. Whether TRE in humans confers additive benefits to disordered metabolism above and beyond those induced by exercise training remains to be determined experimentally.”
Rethinking Milk: Science Takes on the Dairy Dilemma
Brenda Goodman, Medscape – Feb 19, 2020.
“Cow’s milk is creamy, filling, and delicious ice-cold, and decades of advertising have sold it to Americans as a food that “does a body good.” Dairy products are rich in calcium and protein, and they have long been promoted as important for helping kids grow and helping kids and adults build and maintain strong bones. But does dairy deserve its health halo? The current U.S. dietary guidelines recommend that just about everyone eat three servings of dairy a day.
Now, in a new review, Walter Willett, MD, DrPH, a professor of nutrition and epidemiology at the Harvard T.H. Chan School of Public Health, and his co-author, David Ludwig, MD, PhD, a professor of pediatrics and nutrition at Harvard, say the science behind those dietary recommendations is thin. And they say eating too much dairy may cause harm to both our bodies and the planet.
“If we’re going to recommend something, it obviously should be based on strong evidence,” says Willett. He reviewed the risks and benefits of drinking milk for The New England Journal of Medicine. “The basis of calcium recommendations is, I think, fundamentally flawed in the United States,” he says.
He’s not the only one who feels that way.
Elizabeth Jacobs, PhD, is a professor of epidemiology, biostatistics, and nutritional sciences at the University of Arizona Mel & Enid Zuckerman College of Public Health in Tucson. She and her colleagues recently reviewed the science behind the dairy recommendations and concluded that the U.S. should follow Canada’s lead and ditch dairy as a separate food group. Instead, they recommended placing dairy foods in the protein category, making them one choice among many that would help people meet their protein requirements. Their paper is published in Nutrition Reviews.
The two papers come at time when the U.S. dietary guidelines are under review. A new version of the guidelines will be issued by a panel of experts later this year, and for the first time will include advice for pregnant women and for children under age 2.
“We’re not saying milk is dangerous or harmful,” Jacobs says. “No matter how you slice it, Americans are moving away from milk. So let’s adapt to this change and give people more opportunity to meet their nutritional needs.”
Willett also points out that dairy farming is hard on the environment. While that might not have been a big consideration 20 years ago, climate change makes it critical to consider now. “If it’s going to have a major adverse environmental impact, we better take a serious look at our recommendations as well and see what we’re going to do to mitigate that,” he says.
Slim Evidence Behind Dairy’s Health Claims
While we’re drinking less dairy as a beverage, we’re still consuming more of it overall. According to the U.S. Department of Agriculture, the average American ate and drank about 9% more dairy in 2018 than we consumed per person in 1975. Data shows that we’re eating more cheese and yogurt but drinking a lot less milk. Milk consumption has fallen about 40% since 1975. But because it takes more milk to make products like cheese and yogurt, dairy consumption is up overall.
The current dietary guidelines for dairy are based on the idea that we need milk to help meet daily calcium requirements.
Yet Willett says those recommendations come from studies that were relatively small — including just 155 men and women. And those studies were short — following people for 2 to 3 weeks. Researchers measured how much calcium they ate and drank, and compared it to how much they were excreting in stool and urine. The idea was to find out how much calcium the body needs to keep it in balance.
In adults, who are done growing, calcium balance should be net zero. That is, people should excrete about the same amount as they eat or drink. In Americans, who tend to eat a lot of calcium compared to people in other countries, the studies concluded 741 milligrams of calcium a day was enough for balance. In other countries, like Peru, where diets typically aren’t as rich in calcium and dairy products, the amount needed for balance was much less — around 200 milligrams. Willett says this is consistent with the idea that the body can change how much calcium it absorbs from food. When people eat less calcium, the body may simply absorb more to meet its needs.
He also points to large population-based studies that offer snapshots of how people eat and what happens to their health. These kinds of studies have consistently shown that in countries where people eat the most dairy, they also have higher rates of fractures. “That raises sort of a red flag that there’s something wrong here,” Willett says. Those studies can’t prove that eating more dairy causes hip fractures, but Willett believes it makes sense because eating dairy products in childhood is known to accelerate growth and lengthen bones. The risk appears to be highest for men who drank a lot of milk in childhood.
“That’s probably because of basic mechanics. If you have long bones, they’re easier to break than short bones,” he says. Not everyone agrees with the study’s conclusions. In a written statement, the National Dairy Council, which represents dairy farmers, said the study didn’t include the “total body of evidence” on dairy foods. “Dairy remains an important part of a balanced diet and provides lasting and meaningful nourishment for people, the planet and communities,” Gregory Miller, PhD, chief global science officer at the National Dairy Council, said in a written statement. In additional to bone health, milk has been touted as being helpful for weight loss. The review found no evidence to support that. Research shows that dairy products can help control blood pressure, but only when they’re part of an overall healthy diet. That makes it tough to tease out whether milk or dairy products were responsible for the benefit.
Its effects on other health outcomes are mixed. Willett says observational studies have found strong links between eating dairy and some kinds of cancer, such as prostate cancers. Again, these studies can’t show that milk causes cancer. There were no links found between milk and getting diabetes. And there was no link between lifespan and eating dairy. Taken together, the science shows that “milk is not essential for health,” says Marion Nestle, PhD, a retired professor of nutrition, food studies, and public health at New York University who was not involved in the study. “This tells me that milk is a food like any other, meaning that its effects depend on everything else people are eating or doing. People who like milk can continue drinking it. Those who don’t like it don’t have to,” she says. “It’s just a food.” Willett agrees. He says if you’re a dairy underachiever, you shouldn’t worry about it. If you’re not getting any dairy in your diet at all, it’s not a bad idea to take a calcium supplement, but don’t take gobs — 500-600 milligrams a day should be enough.
What About Kids?
“It’s complicated for adults, but it’s even more complicated for kids, and we have even less data,” Willett says. The calcium needs of kids are trickier to figure out. They’re growing, so they’ll naturally need more. But the role dairy should play in meeting their calcium needs isn’t clear.
There is good evidence that kids who drink cow’s milk grow taller than those who don’t. It’s not known exactly how milk accelerates growth. But the study authors say cows are often pregnant when they’re milked, which increases hormones like estrogen and progesterone. Cows have also been bred to produce more of another hormone, called insulin-like growth factor, which increases milk production, but those hormones may also promote growth in people. There’s also some worry that hormones in milk may lead to the cancer later in life, but the evidence for that is mostly circumstantial. Kids need calcium for building strong bones, Willett says, but studies don’t show that adding a lot more dairy makes a difference. One study, for example, randomly assigned 240 kids, ages 8 to 15, who weren’t getting enough calcium in their diets, to a meal plan with three added daily servings of dairy, or to continue on their normal diets. After 18 months, the study found no difference in bone density between the kids who had more dairy and the ones who didn’t. Willett also notes that while the U.S. recommends that kids ages 4 to 8 get 1,000 milligrams of calcium in their diets, the U.K. recommends about half that much, just 450 to 550 milligrams a day.That doesn’t have to come from milk, he says. Other foods like kale, broccoli, tofu, nuts, and beans all count toward the goal. One important point, he says, is if dairy is off the table at your house, make sure your kids are getting vitamin D, though a dietary supplement.
Jean Welsh, PhD, who researches nutrition as an associate professor of pediatrics at Emory University, praised the reviewers for raising important questions about dairy. But she urged caution when it comes to taking dairy off the table for kids. “What always makes me nervous when we talk about these key features of our diets is if we promote a change, what’s going to replace it?” says Welsh, who was not involved in the review.
“The study authors say that if you have a good-quality diet, you don’t need milk. Well, yeah,” Welsh says. “It’s not like we’re eating well.” On average, many kids probably don’t get enough broccoli, kale, or other sources of calcium in their diets to meet all their needs, she says. Milk is better than sugar-sweetened beverages, she says, especially for kids. Welsh recently tested several brands of conventional and organic milk for pesticides, antibiotics, and hormones. While pesticides and antibiotics were sometimes found in the conventionally farmed milk samples, none were found in the organic milk samples. Hormone levels were also higher in the conventionally farmed samples, compared to the organic samples. She says that if organic milk is too pricey, parents shouldn’t worry. Milk is still good for kids. Especially if they’re picky eaters. “While there are advantages to drinking organic milk in that it’s free of chemicals often used in milk production, we do not have evidence that this makes a difference in children’s health,” Welsh says. “What we do know is that milk, organic or not, is a readily available source of nutrients important in the diets of children.”
Environmental Impacts of Dairy
Even if you’ve loved dairy for a long time, there are reasons to reconsider, not least of which is climate change. Willett notes that considering different sources of protein, the costs of dairy to the environment are probably five to 10 times greater than plant-based protein sources. Dairy farms consume more water. They can contribute to water pollution. Large-scale dairies may depend on antibiotics to keep their animals healthy, which contributes to antibiotic resistance in people. He says limiting dairy production would make a “major contribution” to reaching greenhouse gas targets. Some dairy alternatives have their own environmental issues. Almonds, for example, are a water-intensive crop. Miller, of the National Dairy Council, says dairy farmers are working to green their operations. “U.S. dairy only accounts for approximately 2% of total U.S. greenhouse gas emissions. Farmers continue to make even more environmental progress. For example, producing a gallon of milk in 2017 involved 30% less water, 21% less land, 19% smaller carbon footprint and 20% less manure than in 2007,” he says.”
Sources:
Walter Willett, MD, DrPH, professor of nutrition and epidemiology, Harvard T.H. Chan School of Public Health, Cambridge, MA.
Elizabeth Jacobs, PhD, professor of epidemiology, biostatistics, and nutritional sciences, University of Arizona Mel & Enid Zuckerman College of Public Health, Tucson.
Gregory Miller, PhD, chief global science officer, National Dairy Council, Chicago.
Jean Welsh, PhD, associate professor of pediatrics, Emory University, Atlanta.
Marion Nestle, PhD, emerita professor of nutrition, New York University, New York City.
The New England Journal of Medicine: “Milk and Health.”
Nutrition Reviews: “Re-examination of dairy as a single commodity in US dietary guidance.”
