Cybermedlife - Therapeutic Actions Dietary Modification - Caloric Restriction

Curcumin Mimics the Neurocognitive and Anti-Inflammatory Effects of Caloric Restriction in a Mouse Model of Midlife Obesity.

Abstract Title: Curcumin Mimics the Neurocognitive and Anti-Inflammatory Effects of Caloric Restriction in a Mouse Model of Midlife Obesity. Abstract Source: PLoS One. 2015 ;10(10):e0140431. Epub 2015 Oct 16. PMID: 26473740 Abstract Author(s): Marjana Rahman Sarker, Susan Franks, Nathalie Sumien, Nopporn Thangthaeng, Frank Filipetto, Michael Forster Article Affiliation: Marjana Rahman Sarker Abstract: Dietary curcumin was studied for its potential to decrease adiposity and reverse obesity- associated cognitive impairment in a mouse model of midlife sedentary obesity. We hypothesized that curcumin intake, by decreasing adiposity, would improve cognitive function in a manner comparable to caloric restriction (CR), a weight loss regimen. 15-month-old male C57BL/6 mice were assigned in groups to receive the following dietary regimens for 12 weeks: (i) a base diet (Ain93M) fed ad libitum (AL), (ii) the base diet restricted to 70% of ad libitum (CR) or (iii) the base diet containing curcumin fed AL (1000 mg/kg diet, CURAL). Blood markers of inflammation, interleukin 6 (IL-6) and C-reactive protein (CRP), as well as an indicator of redox stress (GSH: GSSG ratio), were determined at different time points during the treatments, and visceral and subcutaneous adipose tissue were measured upon completion of the experiment. After 8 weeks of dietary treatment, the mice were tested for spatial cognition (Morris water maze) and cognitive flexibility (discriminated active avoidance). The CR group showed significant weight loss and reduced adiposity, whereas CURAL mice had stable weight throughout the experiment, consumed more food than the AL group, with no reduction of adiposity. However, both CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and GSH as well as the GSH: GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. The results suggest that, independent of their effects on adiposity; dietary curcumin and caloric restriction have positive effects on frontal cortical functions that could be linked to anti-inflammatory or antioxidant actions. Article Published Date : Dec 31, 2014

Food scarcity, neuroadaptations, and the pathogenic potential of dieting in an unnatural ecology: binge eating and drug abuse.

Abstract Title: Food scarcity, neuroadaptations, and the pathogenic potential of dieting in an unnatural ecology: binge eating and drug abuse. Abstract Source: Physiol Behav. 2011 Jul 25 ;104(1):162-7. Epub 2011 Apr 28. PMID: 21530562 Abstract Author(s): Kenneth D Carr Article Affiliation: Department of Psychiatry, Millhauser Laboratories, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: In the laboratory, food restriction has been shown to induce neuroadaptations in brain reward circuitry which are likely to be among those that facilitate survival during periods of food scarcity in the wild. However, the upregulation of mechanisms that promote foraging and reward-related learning may pose a hazard when food restriction is self-imposed in an ecology of abundant appetitive rewards. For example, episodes of loss of control during weight-loss dieting, use of drugs with addictive potential as diet aids, and alternating fasting with alcohol consumption in order to avoid weight gain, may induce synaptic plasticity that increases the risk of enduring maladaptive reward-directed behavior. In the present mini-review, representative basic research findings are outlined which indicate that food restriction alters the function of mesoaccumbens dopamine neurons, potentiates cellular and behavioral responses to D-1 and D-2 dopamine receptor stimulation, and increases stimulus-induced synaptic insertion of AMPA receptors in nucleus accumbens. Possible mechanistic underpinnings of increased drug reward magnitude, drug-seeking, and binge intake of sucrose in food-restricted animal subjects are discussed and possible implications for human weight-loss dieting are considered. Article Published Date : Jul 25, 2011

Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance.

Abstract Title: Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance. Abstract Source: Free Radic Biol Med. 2011 Jul 21. Epub 2011 Jul 21. PMID: 21816219 Abstract Author(s): Fernanda M Cerqueira, Fernanda M da Cunha, Camille C Caldeira da Silva, Bruno Chausse, Renato L Romano, Camila C M Garcia, Pio Colepicolo, Marisa H G Medeiros, Alicia J Kowaltowski Abstract: Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feeding promoted glucose intolerance, without a loss in insulin receptor phosphorylation. Intermittent feeding substantially increased insulin receptor nitration in both intra-abdominal adipose tissue and muscle, a modification associated with receptor inactivation. All restricted diets enhanced nitric oxide synthase levels in the insulin-responsive adipose tissue and skeletal muscle. However, whereas calorie restriction improved tissue redox state, food restriction and intermittent feedings did not. In fact, long-term intermittent feeding resulted in largely enhanced tissue release of oxidants. Overall, our results show that restricted diets are significantly different in their effects on glucose tolerance and redox state when adopted long-term. Furthermore, we show that intermittent feeding can lead to oxidative insulin receptor inactivation and glucose intolerance. Article Published Date : Jul 21, 2011

Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes.

Abstract Title: Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes. Abstract Source: Diabet Med. 2011 May;28(5):549-59. PMID: 21480966 Abstract Author(s): H Kahleova, M Matoulek, H Malinska, O Oliyarnik, L Kazdova, T Neskudla, A Skoch, M Hajek, M Hill, M Kahle, T Pelikanova Article Affiliation: Institute for Clinical and Experimental Medicine Charles University, 1st Faculty of Medicine Institute of Endocrinology, Prague, Czech Republic. Abstract: Diabet. Med. 28, 549-559 (2011) ABSTRACT: Aims  The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods  A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted(-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results  Forty-three per cent of participants in the experimental group and 5% of participants in the control groupreduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental groupthan in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions  A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet. Article Published Date : May 01, 2011

Low calorie dieting increases cortisol.

Abstract Title: Low calorie dieting increases cortisol. Abstract Source: Psychosom Med. 2010 May;72(4):357-64. Epub 2010 Apr 5. PMID: 20368473 Abstract Author(s): A Janet Tomiyama, Traci Mann, Danielle Vinas, Jeffrey M Hunger, Jill Dejager, Shelley E Taylor Article Affiliation: Robert Wood Johnson Foundation Health and Society Scholars Program, University of California, San Francisco, San Francisco, California 94118, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: OBJECTIVE: To test the hypothesis that dieting, or the restriction of caloric intake, is ineffective because it increases chronic psychological stress and cortisol production--two factors that are known to cause weight gain; and to examine the respective roles of the two main behaviors that comprise dieting--monitoring one's caloric intake and restricting one's caloric intake--on psychological and biological stress indicators. METHODS: In a 2 (monitoring vs. not) x 2 (restricting vs. not) fully crossed, controlled experiment, 121 female participants were assigned randomly to one of four dietary interventions for 3 weeks. The monitoring + restricting condition tracked their caloric intake and restricted their caloric intake (1200 kcal/day); the monitoring only condition tracked their caloric intake but ate normally; the restricting only condition was provided 1200 kcal/day of food but did not track their calories, and the control group ate normally and did not track their intake. Before and after the interventions, participants completed measures of perceived stress and 2 days of diurnal saliva sampling to test for cortisol. RESULTS: Restricting calories increased the total output of cortisol, and monitoring calories increased perceived stress. CONCLUSIONS: Dieting may be deleterious to psychological well-being and biological functioning, and changes in clinical recommendations may be in order. Article Published Date : May 01, 2010
Therapeutic Actions DIETARY MODIFICATION Caloric Restriction

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Do Food Preferences Change After Bariatric Surgery?

Related Articles Do Food Preferences Change After Bariatric Surgery? Curr Atheroscler Rep. 2017 Sep;19(9):38 Authors: Gero D, Steinert RE, le Roux CW, Bueter M Abstract PURPOSE OF REVIEW: Insights into physiological mechanisms responsible for weight loss after bariatric surgery (BS) have challenged the traditional view that mechanical restriction and caloric malabsorption are major drivers of weight loss and health benefits after BS. Altered diet selection with an increased postoperative preference for low-sugar and low-fat food has also been implicated as a potential mechanism beyond mere reduction of calorie intake. However, the empirical support for this phenomenon is not uniform and evidence is largely based on indirect measurements, such as self-reported food intake data, which are prone to inaccuracy due to their subjective character. RECENT FINDINGS: Most studies indicate that patients not only reduce their caloric intake after BS, but also show a reduced preference of food with high sugar and high fat content. So far, standard behavioral tests to directly measure changes in food intake behavior after BS have been mainly used in animal models. It remains unclear whether there are fundamental shifts in the palatability of high-fat and sugary foods after BS or simply a decrease in the appetitive drive to ingest them. Studies of appetitive behavior in humans after BS have produced equivocal results. Learning processes may play a role as changes in diet selection seem to progress with time after surgery. So far, direct measures of altered food selection in humans after BS are rare and the durability of altered food selection as well as the role of learning remains elusive. PMID: 28779431 [PubMed - indexed for MEDLINE]

Calorie restriction in rodents: Caveats to consider.

Related Articles Calorie restriction in rodents: Caveats to consider. Ageing Res Rev. 2017 Oct;39:15-28 Authors: Ingram DK, de Cabo R Abstract The calorie restriction paradigm has provided one of the most widely used and most useful tools for investigating mechanisms of aging and longevity. By far, rodent models have been employed most often in these endeavors. Over decades of investigation, claims have been made that the paradigm produces the most robust demonstration that aging is malleable. In the current review of the rodent literature, we present arguments that question the robustness of the paradigm to increase lifespan and healthspan. Specifically, there are several questions to consider as follows: (1) At what age does CR no longer produce benefits? (2) Does CR attenuate cognitive decline? (3) Are there negative effects of CR, including effects on bone health, wound healing, and response to infection? (4) How important is schedule of feeding? (5) How long does CR need to be imposed to be effective? (6) How do genotype and gender influence CR? (7) What role does dietary composition play? Consideration of these questions produce many caveats that should guide future investigations to move the field forward. PMID: 28610949 [PubMed - indexed for MEDLINE]

Dietary protein, aging and nutritional geometry.

Related Articles Dietary protein, aging and nutritional geometry. Ageing Res Rev. 2017 Oct;39:78-86 Authors: Simpson SJ, Le Couteur DG, Raubenheimer D, Solon-Biet SM, Cooney GJ, Cogger VC, Fontana L Abstract Nearly a century of research has shown that nutritional interventions can delay aging and age- related diseases in many animal models and possibly humans. The most robust and widely studied intervention is caloric restriction, while protein restriction and restriction of various amino acids (methionine, tryptophan) have also been shown to delay aging. However, there is still debate over whether the major impact on aging is secondary to caloric intake, protein intake or specific amino acids. Nutritional geometry provides new perspectives on the relationship between nutrition and aging by focusing on calories, macronutrients and their interactions across a landscape of diets, and taking into account compensatory feeding in ad libitum-fed experiments. Nutritional geometry is a state-space modelling approach that explores how animals respond to and balance changes in nutrient availability. Such studies in insects and mice have shown that low protein, high carbohydrate diets are associated with longest lifespan in ad libitum fed animals suggesting that the interaction between macronutrients may be as important as their total intake. PMID: 28274839 [PubMed - indexed for MEDLINE]

Nutritional adequacy of diets for adolescents with overweight and obesity: considerations for dietetic practice.

Related Articles Nutritional adequacy of diets for adolescents with overweight and obesity: considerations for dietetic practice. Eur J Clin Nutr. 2017 May;71(5):646-651 Authors: Lister NB, Gow ML, Chisholm K, Grunseit A, Garnett SP, Baur LA Abstract BACKGROUND/OBJECTIVES: Adolescents have unique nutrient requirements due to rapid growth and development. High rates of obesity in adolescents require a variety of diet interventions to achieve weight loss under clinical supervision. The aim of this study is to examine the nutritional adequacy of energy-restricted diets for adolescents. SUBJECTS/METHODS: Three popular diets were modelled for 7 days and assessed by comparing the nutrient profile to the Australian Nutrient Reference Values. Three diets were: (1) a standard energy restricted diet based on current dietary guidelines; (2) a modified carbohydrate diet; and (3) a modified alternate day fasting diet. RESULTS: Initial modelling revealed limiting nutrients (that is, not meeting the recommended intakes) across the diets. Subsequent modelling was required to achieve nutritional adequacy for all three diets. The dietary guidelines diet design met most nutrient targets except essential fatty acids before subsequent modelling, however this diet also provided the highest energy (8.8 vs 8.0 MJ and 6.8 MJ for the modified carbohydrate and modified alternate day fasting diet, respectively). CONCLUSIONS: Energy-restricted diets need careful consideration to meet nutritional requirements of adolescents. A variety of eating patterns can be adapted to achieve nutritional adequacy and energy restriction, however health practitioners need to consider adequacy when prescribing diet interventions for weight loss during adolescence. PMID: 28225054 [PubMed - indexed for MEDLINE]

Nutrition, metabolism, and targeting aging in nonhuman primates.

Related Articles Nutrition, metabolism, and targeting aging in nonhuman primates. Ageing Res Rev. 2017 Oct;39:29-35 Authors: Balasubramanian P, Mattison JA, Anderson RM Abstract This short review focuses on the importance of nonhuman primate nutrition and aging studies and makes the case that a targeted expansion of the use of this highly translatable model would be advantageous to the biology of aging field. First, we describe the high degree of similarity of the model in terms of aging phenotypes including incidence and prevalence of common human age-related diseases. Second, we discuss the importance of the nonhuman primate nutrition and aging studies and the extent to which the outcomes of two ongoing long-term studies of caloric restriction are congruent with short-term equivalent studies in humans. Third, we showcase a number of pharmacological agents previously employed in nonhuman primate studies that display some potential as caloric restriction mimetics. Finally, we present nonhuman primates as an important model for translation of mechanisms of delayed aging identified in studies of shorter-lived animals. Proof of efficacy and safety of candidate longevity agents in nonhuman primates would be a cost-effective means to bring these exciting new avenues a step closer to clinical application. PMID: 28219777 [PubMed - indexed for MEDLINE]

Dietary restriction and lifespan: Lessons from invertebrate models.

Related Articles Dietary restriction and lifespan: Lessons from invertebrate models. Ageing Res Rev. 2017 Oct;39:3-14 Authors: Kapahi P, Kaeberlein M, Hansen M Abstract Dietary restriction (DR) is the most robust environmental manipulation known to increase active and healthy lifespan in many species. Despite differences in the protocols and the way DR is carried out in different organisms, conserved relationships are emerging among multiple species. Elegant studies from numerous model organisms are further defining the importance of various nutrient-signaling pathways including mTOR (mechanistic target of rapamycin), insulin/IGF-1-like signaling and sirtuins in mediating the effects of DR. We here review current advances in our understanding of the molecular mechanisms altered by DR to promote lifespan in three major invertebrate models, the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, and the fruit fly Drosophila melanogaster. PMID: 28007498 [PubMed - indexed for MEDLINE]

Impact of intermittent fasting on health and disease processes.

Related Articles Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017 Oct;39:46-58 Authors: Mattson MP, Longo VD, Harvie M Abstract Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging. PMID: 27810402 [PubMed - indexed for MEDLINE]

Cutting back on the essentials: Can manipulating intake of specific amino acids modulate health and lifespan?

Related Articles Cutting back on the essentials: Can manipulating intake of specific amino acids modulate health and lifespan? Ageing Res Rev. 2017 Oct;39:87-95 Authors: Brown-Borg HM, Buffenstein R Abstract With few exceptions, nutritional and dietary interventions generally impact upon both old-age quality of life and longevity. The life prolonging effects, commonly observed with dietary restriction reportedly are linked to alterations in protein intake and specifically limiting the dietary intake of certain essential amino acids. There is however a paucity of data methodically evaluating the various essential amino acids on health- and lifespan and the mechanisms involved. Rodent diets containing either lower methionine content, or tryptophan, than that found in commercially available chow, appear to elicit beneficial effects. It is unclear whether all of these favorable effects associated with restricted intake of methionine and tryptophan are due to their specific unique properties or if restriction of other essential amino acids, or proteins in general, may produce similar results. Considerably more work remains to be done to elucidate the mechanisms by which limiting these vital molecules may delay the onset of age-associated diseases and improve quality of life at older ages. PMID: 27570078 [PubMed - indexed for MEDLINE]

The Effects of a Gluten-free Diet Versus a Hypocaloric Diet Among Patients With Fibromyalgia Experiencing Gluten Sensitivity-like Symptoms: A Pilot, Open-Label Randomized Clinical Trial.

Related Articles The Effects of a Gluten-free Diet Versus a Hypocaloric Diet Among Patients With Fibromyalgia Experiencing Gluten Sensitivity-like Symptoms: A Pilot, Open-Label Randomized Clinical Trial. J Clin Gastroenterol. 2017 Jul;51(6):500-507 Authors: Slim M, Calandre EP, Garcia-Leiva JM, Rico-Villademoros F, Molina-Barea R, Rodriguez-Lopez CM, Morillas-Arques P Abstract BACKGROUND AND AIMS: Patients with fibromyalgia frequently present with symptoms similar to those experienced by patients with gluten-related disorders, raising the possibility that a subgroup of these patients could be experiencing underlying gluten sensitivity. This study aimed to evaluate the effects of a gluten-free diet (GFD) compared with a hypocaloric diet (HCD) among patients with fibromyalgia. METHODS: Adult patients diagnosed with fibromyalgia were randomly allocated to receive a GFD or a HCD over a 24-week period. The primary outcome measure was the change in the number of gluten sensitivity symptoms. The following secondary outcomes were evaluated: body mass index, Revised Fibromyalgia Impact Questionnaire, Pittsburgh Sleep Quality Index, Brief Pain Inventory, Beck Depression Inventory-II, State-Trait Anxiety Inventory, Short-Form Health Survey, Patient Global Impression Scale of Severity, Patient Global Impression Scale of Improvement, and adverse events. RESULTS: Seventy-five subjects were randomly allocated to receive either a GFD (n=35) or an HCD (n=40). The least squares mean change in the total number of gluten sensitivity symptoms from baseline did not differ significantly between the GFD and HCD groups (-2.44±0.40 for the GFD; -2.10±0.37 for the HCD; P=0.343). Similarly, the 2 dietary interventions did not differ in any of the remaining measured secondary outcomes. Both dietary interventions were well tolerated. CONCLUSIONS: Both dietary interventions were associated with similar beneficial outcomes in reducing gluten sensitivity symptoms and other secondary outcomes. However, despite its specificity, GFD was not superior to HCD in reducing the number of gluten sensitivity symptoms or secondary outcomes. PMID: 27548732 [PubMed - indexed for MEDLINE]

Calorie restriction in humans: An update.

Related Articles Calorie restriction in humans: An update. Ageing Res Rev. 2017 Oct;39:36-45 Authors: Most J, Tosti V, Redman LM, Fontana L Abstract Calorie restriction (CR), a nutritional intervention of reduced energy intake but with adequate nutrition, has been shown to extend healthspan and lifespan in rodent and primate models. Accumulating data from observational and randomized clinical trials indicate that CR in humans results in some of the same metabolic and molecular adaptations that have been shown to improve health and retard the accumulation of molecular damage in animal models of longevity. In particular, moderate CR in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases, and cancer, the leading causes of morbidity, disability and mortality. In this paper, we will discuss the effects of CR in non-obese humans on these physiological parameters. Special emphasis is committed to recent clinical intervention trials that have investigated the feasibility and effects of CR in young and middle-aged men and women on parameters of energy metabolism and metabolic risk factors of age-associated disease in great detail. Additionally, data from individuals who are either naturally exposed to CR or those who are self-practicing this dietary intervention allows us to speculate on longer-term effects of more severe CR in humans. PMID: 27544442 [PubMed - indexed for MEDLINE]