Katarina Tomljenović Borer

Milk was designed by evolution to provide superior nutrition for support of growth and development of mammalian young. When humans domesticated dairy cattle about 10,500 years ago, they also adopted milk for adult consumption and learned to separate and utilize its constituent parts, milk proteins whey and casein for muscle growth, milk fermentation to make kefir, yogurt, and cheese, and milkfat to make butter. Research on how consumption of these different milk products affects human health has generated much factual data and some uncertainties and controversies about the extent it can be used to improve adult human body and overall metabolic health. This is important in the context of global burden of high cardiovascular morbidity and concerns about any impact of milkfat consumption on cardiovascular (CVD) and coronary heart diseases (CHD). The first theme of this review examines the involvement of milk proteins whey and casein on skeletal muscle hypertrophy (MHT). The major contribution of resistance training (RET) to MHT is contrasted to the lesser, but still important, contribution of protein supplementation (PS) and uncertainties about the efficacy of the milk proteins relative to plant proteins, along with dose, training status, and timing of PS relative to RET in producing MHT. The exceptionally rich concentration of essential and branched-chain amino acids makes whey protein and casein highly effective but not essential for MHT which can also be achieved with higher quality plant PS and is not critically dependent on either the timing of PS, the training status, or the age of users. The second theme examines the nature and importance of milk fermentation in production of full-fat and low-fat yogurt, kefir, and cheese in terms of bacteria involved, their metabolism in the gut, their beneficial influence on the gut microbiome (GM) and on overall as well as cardiovascular health. Lastly, milkfat as influence on cardiovascular health is discussed both from the perspective of its effects on blood lipids and cardiovascular physiology, but also as a component of the complex dairy matrices. As part of a rich nutrient matrix, milk products provide benefits to cardiovascular health because of their biologically active proteins and fatty acids which exert anti-inflammatory, anti-carcinogenic, antioxidative, and other beneficial actions, despite their high fat content and level of fat saturation. Fermentation usually lowers CVD and CHD risks of full-fat milk and its products, but health benefits often are greater when their fat content is reduced. Butter does not benefit from the biological activities of the milk proteins and is not fermented, so when consumed in large quantities, the balance of cardiovascular benefits shifts toward higher CVD and CHD risk. Three knowledge gaps need to be corrected for a better understanding of health benefits of consumption of milk products. Individual nutrient components in dairy food matrices need to be measured and recognized. Their identity needs to be linked to a better understanding of how they influence atherogenic lipoproteins and protein synthesis. And maximal consumption limits need to be defined for full-fat milk products to assure the benefits that their biologically active components offer, but also to reduce their detrimental effects on cardiovascular risk factors. Overall, as a food category, milk products justify acceptance as a healthy natural source of nutrition that was evolutionarily designed to support early growth and development of mammalian young but need to be prudently implemented for their lifelong consumption in adulthood.

Milk is the principal nutrient of newborn humans and a diagnostic feature of the order Mammalia. Its release is elicited as a reflex by infant sucking under the control of the hormone oxytocin. While it is recognized that breast milk optimally promotes infant longitudinal growth and development, this review explores facts and controversies regarding the extent to which the milks of several dairy animals and infant formula milk (IF) approximate special properties and bioactivities of breast milk. It also provides evidence that early exposure to undernutrition during the very rapid fetal and early infancy growth predominantly and permanently stunts longitudinal growth trajectory in both animals and humans and is often followed in later life by obesity and metabolic dysfunction, and sometimes also by precocious timing of sexual maturation. There is a knowledge gap as to whether there may be additional critical periods of nutritional vulnerability in human development, which is characterized by a relatively prolonged period of slow childhood growth bracketed by the rapid fetal–neonatal and pubertal growth spurts. It is also unclear whether any quantitative differences in caloric intake and supply during neonatal period may influence developmental fatness programming. A further knowledge gap exists regarding the role of infant microbiome composition and development in the possible epigenetic programming of longitudinal growth or fatness in later life. Extending the research of early developmental programming to the entire period of human growth from conception to the end of puberty, examining infant caloric intake and supply as possible factors modulating the epigenetic programming in favor of obesity, and examining the role of infant gut microbiome in developing infant’s capacity to process nutrients may provide a better understanding of the interaction between critical nutritional influences in the control of human longitudinal growth and later-life obesity.

Milk is the principal nutrient of newborn humans and a diagnostic feature of the order mammalia. Its release is elicited reflexly by infant sucking under the control of hormone oxytocin. While it is recognized that breast milk optimally promotes infant longitudinal growth and development, this review explores facts and controversies regarding the extent to which the milks of several domesticated animals and formula milk approximate special properties and bioactivities of breast milk. The review provides evidence that early exposure to undernutrition during pregnancy and infancy predominantly and permanently stunts longitudinal growth in both animals and humans, but is often accompanied later in life by obesity and metabolic dysfunction, and sometimes also by altered timing of sexual maturation. There is insufficient understanding of the relationship between critical periods of nutritional vulnerability and the control of longitudinal growth in humans this growth is characterized by a relatively prolonged period of slow childhood growth bracketed by two rapid neonatal and pubertal growth phases. It is not known whether there are additional critical nutritional periods during the extended and variable phases of human growth beyond the intrauterine and the early postnatal ones. It also is not clear how long the qualitative and quantitative characteristics of infant milk intake can influence subsequent periods of childhood and pubertal growth and development. Metabolic consequences of the macronutrient and hormonal composition of human milk during the critical early under- or over-nutrition will be better understood in studies linking the interactions of nutrient properties to controls of linear growth and body composition over the extended period of human growth from infancy through the end of puberty.

Intermittent fasting (IF) approach to weight loss obviates the inconvenience of calorie counting required in daily caloric restriction (DCR). A metabolic defense mechanism (MDM) obstructs weight loss and facilitates weight regain possibly by increasing hunger and efficiency of exercise energy expenditure (EEf), and by reducing resting metabolic rate (RMR) and energy expenditure (EE) including physical activity (PA). IF may test whether its paradigm can better counteract MDM than DCR. A knowledge gap exists about whether the duration of weekly uninterrupted fasts (UFs), when the IF protocols are isocaloric, affects the MDM. The aim and objective of this 82-week study were to determine whether 36 hours of near-absolute twice-weekly UF will exacerbate MDM but generate similar rates of weight and fat losses compared to four IF studies featuring 20 hours of weekly UF with both IF protocols matched for weekly hours of fast (108) and free access to food (60), a fasting-to-eating (F/E) ratio of 1.8. This case report presents results of twice-weekly fasting on non-consecutive days (5:2-NC) and compares them to results from a 4:3-NC protocol with a 20-hour UF caused by a modification of providing a 500-600 kcal meal on three fasting days (M4:3-NC). Because the large meal raises insulin concentration for four hours at the start of the fasting day, the 20-hour UF consists of the remaining eight hours on the fasting day, followed by 12 additional nocturnal hours of fasting. The hypotheses were that (1) because of their matched F/E ratio, the rates of weight and fat losses will be similar in both protocols, and (2) because of its longer UF period, hunger will be higher and RMR and EE will be lower, in 5:2-NC than in M4:3-NC protocol. The main findings were that the 5:2-NC protocol produced (1) slower rates of weight and fat losses, (2) modest reduction in the sensation of hunger and substantial decline in fullness, (3) no change in RMR and EE, and (4) fourfold post-fast increase in the circulating concentration of the ketone body ß-hydroxybutyrate (BHB), 2.5 greater than in the M4:3-NC protocol. The absence of increased hunger and changes in EE, the variability of the rate of weight loss in the 5:2-NC protocol, plus increased EEf in one M4:3-NC study, suggest that IF does not mitigate MDM, but that shortened UF period in M4:3-NC reduces the rise in BHB. Thus, the addition of a large meal on fasting days is unnecessary for the prevention of hunger and is counterproductive for increases in BHB and its potential health benefits. Continuous practice of the 5:2-NC protocol allows sustained weight loss and maintenance of lost weight with diminished hunger for as long as it is implemented.

Background. Bone Health and Osteoporosis Foundation (BHOF) reports that as of 2023, approximately 10 million of older Americans have osteoporosis and another 44 million have low bone density. Osteoporosis is a serious handicap for the elderly and, in particular, for estrogen-deficient postmenopausal women, as it increases the risk of debilitating bone weakness and fractures. The BHOF recommendations for prevention of osteopenia, osteoporosis and bone fractures are to perform weight-bearing and muscle-strengthening exercises and to take recommended amounts of daily calcium and vitamin D. Methods. The purpose of this review is to describe and discuss recent evidence-based research on how to effectively utilize timing of exercise and calorie intake for stimulation of postmenopausal bone anabolism, and to provide this new information in the form of specific and actionable recommendations. Results. The five evidence-based recommendations are as follows: 1. Select an appropriate circadian time of day for exercise; 2. Increase walking speed to raise the movement momentum; 3. Eat a weight-maintenance meal one or two hours before the exercise bout; 4. Sustain the duration of walking activity (impulse) for 40 to 45 min; and 5. Repeat effective exercise stimulus 7 to 8 h after the first one to double the anabolic effect. Osteogenesis can also be increased with subthreshold mechanical loading, where needed, under several special circumstances. Conclusions. This review should provide pragmatic actionable pointers on how to utilize the idiosyncratic bone responsiveness to timing of movement and meals to prevent osteoporosis and encourage research toward a better understanding of how bone detects adequacy of a mechanical stimulus and determines duration of necessary rest to recover its sensitivity to mechanical stimulation and nutrients.

Editorial: Integrative exercise endocrinology

Intermittent fasting (IF) approach for weight loss obviates the inconvenience of calorie counting of daily caloric restriction (DCR). It tests IF ability to better counteract a metabolic defense mechanism (MDM) than DCR. MDM obstructs weight loss and facilitates weight regain possibly by increasing hunger and efficiency of exercise energy expenditure (EEf), and by reducing resting metabolic rate (RMR) and physical activity (PA). A knowledge gap exists about whether the duration of weekly uninterrupted fasts (UFs), where the IF protocols are isocaloric, mitigate the MDM. This study compares two IF protocols that have the same weekly number of hours of fast (108) and free access to food (60), but which differ in the duration of UF. An 82-week case report was conducted with twice-weekly near-absolute 36-hour fasts on non-consecutive days (5:2-NC) and compared to ten studies with a 20-hour UF on three non-consecutive days (4:3-NC) modified through provision of a 500–600 kcal meal on fasting days. The large meal raised insulin concentration for 4 hours and reduced the UF to 8 hours followed by 12 nocturnal hours of fasting. The hypotheses were that (1) because of their matched F/E ratio, the rates of weight and fat losses will be similar in both protocols, and (2) because of its longer UF period, hunger will be higher and RMR and voluntary physical activity lower, in 5:8-NC than in M4:3-NC protocol,. The main differences between the two protocols were, (1) slower rates of weight and fat losses, (2) lower sensation of hunger and substantial decline in fullness, no change in RMR and physical activity, and 2.5 times higher post-fast concentration of the ketone body beta-hydroxybutyrate (BHB) in 8:2-NC compared to M4:3-NC protocol. Absence of increased hunger and the variability of the rate of weight loss in 5:2-NC protocol, plus increased EEf in one M4:3-NC study suggest that IF does not curtail MDM, but shortened UF period in M4:3-NC reduces elicitation of BHB. Thus, the addition of a large meal on fasting days is unnecessary for prevention of hunger and is counterproductive for increases in BHB and its potential health benefits.

Introduction: This study had two aims: (1) To confirm the efficacy of exercise speed and impulse (session duration at a given speed) to produce total and abdominal fat loss in postmenopausal women, and (2) compare the exercise speed and impulse necessary for the stimulation of fat loss to the suppression of bone mineral loss. Of special interest was to compare these parameters of exercise on fat loss in the same study and with the same subjects where they were found to suppress bone mineral loss. We hypothesized that (1) more total fat will be lost with slow walking and a longer impulse than with fast speed and shorter impulse, and (2) more abdominal subcutaneous (SC) and visceral fat (VF) will be lost with fast walking speed. Materials and Methods: Fat loss and suppression of bone mineral loss were measured in the same 25 subjects after 15 weeks, and fat measurements were also taken after 30 weeks in 16 residual subjects. Study parameters were walking a 4.8 km distance 4 days/week at either 6.6 km/h (120% of ventilatory threshold (VT)) or at 5.5 km/h (101.6% of VT) and expending 300 kcal/session. Body composition (fat and lean body mass, LBM) was measured with dual-energy X-ray absorptiometry (DXA) and anthropometric methods. Results: Slow walkers in the residual group progressively lost a significant percent of total body fat over 30 weeks while no such loss occurred after 15 weeks in fast walkers in either group, supporting hypothesis 1. However, the 20% higher starting body fat in 16 residual slow relative to fast subjects suggests that exercise fat loss is greater in overweight than in lean subjects. In fast walkers, fat loss occurred after 30 weeks of training. Hypothesis 2 was not supported as both speeds led to equal VF loss in 30-week group as estimated by waist circumference (CF) confirming that VF responds to the magnitude of energy expenditure and not the walking speed. Conclusions: Total body fat is lost through walking at all speeds, but the change is more rapid, clear, and initially greater with slow walking in overweight subjects. A longer exercise impulse at a lower speed in our study initially produced greater total fat loss than a shorter one with fast walking speed. This was reversed in comparison to how the same exercise in the same subjects suppressed bone mineral loss. Data from other studies indicate that longer impulses may promote greater fat loss at both slow and high exercise speeds, and our study providing only a 4.8 km walking distance may have limited the walking impulse and the magnitude of fat loss. Increased exercise energy expenditure at either walking speed produces equivalent declines in visceral fat in postmenopausal women, and with sufficiently long impulses, should reduce disabilities associated with central obesity.

The current prevalence of obesity in the US is strongly associated with excessive food intake and insufficient physical activity. This study examined whether changing the timing of exercise before or after two daily meals could alter human appetite for food. Fifty-four healthy postmenopausal women were matched by body weight and assigned to two groups: (1) two bouts of 2-h moderate-intensity exercise ending one hour before each weight-maintenance meal (XM, n = 23), (2) two-hour moderate-intensity exercise starting 1 h after each weight-maintenance meal (MX, n = 23), and one sedentary control (SED) arm (n = 8). Measurements included appetite ratings, circulating glucose, free fatty acids (FFAs), a ketone body D-ß-hydroxybutyrate (BHB), glucoregulatory hormones insulin and glucagon, and gastrointestinal hormones associated with food digestion and absorption and implicated in appetite sensations. XM group increased concentrations of FFAs and BHB during exercise and increased insulin and homeostatic assessment of insulin resistance (HOMA-IR) during postprandial periods. MX group reduced postprandial insulin and HOMA-IR by about 50% without a major change in plasma glucose. There was brief suppression of hunger and an increase in satiation in both exercise groups near the end of the first postprandial period. The time course of hunger was unrelated to the perturbations in fuel metabolism, depletion of liver glycogen, and not correlated with concentration changes in hunger-stimulating hormone ghrelin during XM exercise before meals. Similarly, there was no correlation between the time course of fullness during exercise after meals with the postprandial secretion of gastrointestinal hormones including cholecystokinin (CCK) that has been linked to satiation. Hunger and satiation appear to depend on oral intake and gastrointestinal processing of nutrients and are not affected by metabolic and hormonal consequences of the timing of exercise with respect to meals. Moderate-intensity exercise performed shortly after meals induces a rapid and highly effective lowering of insulin resistance.

The intent of this review is to survey physiological, psychological, and societal obstacles to the control of eating and body weight maintenance and offer some evidence-based solutions. Physiological obstacles are genetic and therefore not amenable to direct abatement. They include an absence of feedback control against gaining weight; a non-homeostatic relationship between motivations to be physically active and weight gain; dependence of hunger and satiation on the volume of food ingested by mouth and processed by the gastrointestinal tract and not on circulating metabolites and putative hunger or satiation hormones. Further, stomach size increases from overeating and binging, and there is difficulty in maintaining weight reductions due to a decline in resting metabolism, increased hunger, and enhanced efficiency of energy storage. Finally, we bear the evolutionary burden of extraordinary human capacity to store body fat. Of the psychological barriers, human craving for palatable food, tendency to overeat in company of others, and gullibility to overeat when offered large portions, can be overcome consciously. The tendency to eat an unnecessary number of meals during the wakeful period can be mitigated by time-restricted feeding to a 6–10 hour period. Social barriers of replacing individual physical work by labor-saving appliances, designing built environments more suitable for car than active transportation; government food macronutrient advice that increases insulin resistance; overabundance of inexpensive food; and profit-driven efforts by the food industry to market energy-dense and nutritionally compromised food are best overcome by informed individual macronutrient choices and appropriate timing of exercise with respect to meals, both of which can decrease insulin resistance. The best defense against overeating, weight gain, and inactivity is the understanding of factors eliciting them and of strategies that can avoid and mitigate them.