Severe Caloric Restriction Research Articles

From starvation to time-restricted eating: a review of fasting physiology.

We have long known that subjects with obesity who fast for several weeks survive. Calculations that assume the brain can only use glucose indicated that all carbohydrate and protein sources would be consumed by the brain within several weeks yet subjects with obesity who fasted for several weeks survived. This anomaly led to the determination of the metabolic role of ketone bodies. Subsequent studies transformed our understanding of ketone bodies and illustrated the value of challenging the norm and adapting theory to evidence. Although prolonged fasting is no longer a treatment for obesity, the early studies of starvation provided valuable insights about macronutrient metabolism and ketone body adaptations that fasting elicits. Intermittent fasting and its variants such as time-restricted eating are fasting models that are far less regimented than starvation and severe calorie restriction; yet they produce metabolic benefits. The mechanisms that produce the metabolic changes that intermittent fasting elicits are relatively unknown. In this article, we review the physiology of starvation, starvation adaptation diets, diet-induced ketosis, and intermittent fasting. Understanding the premise and physiology that these regimens induce is necessary to draw parallels and provoke thoughts on the mechanisms underlying the metabolic benefits of intermittent fasting and its variants.

A Systematic Review and Meta-Analysis of the Effect of Caloric Restriction on Skeletal Muscle Mass in Individuals with, and without, Type 2 Diabetes.

Severe caloric restriction interventions (such as very-low-calorie diets) are effective for inducing significant weight loss and remission of type 2 diabetes (T2DM). However, suggestions of associated significant muscle mass (MM) loss create apprehension regarding their widespread use. We conducted a systematic review and meta-analysis to provide a quantitative assessment of their effect on measures of MM in individuals with, or without, T2DM. EMBASE, Medline, Pubmed, CINAHL, CENTRAL and Google Scholar were systematically searched for studies involving caloric restriction interventions up to 900 kilocalories per day reporting any measure of MM, in addition to fat mass (FM) or body weight (BW). Forty-nine studies were eligible for inclusion, involving 4785 participants. Individuals with T2DM experienced significant reductions in MM (WMD -2.88 kg, 95% CI: -3.54, -2.22; p < 0.0001), although this was significantly less than the reduction in FM (WMD -7.62 kg, 95% CI: -10.87, -4.37; p < 0.0001). A similar pattern was observed across studies involving individuals without T2DM. MM constituted approximately 25.5% of overall weight loss in individuals with T2DM, and 27.5% in individuals without T2DM. Subgroup analysis paradoxically revealed greater BW and FM reductions with less restrictive interventions. Our review suggests that caloric restriction interventions up to 900 kilocalories per day are associated with a significant reduction in MM, albeit in the context of a significantly greater reduction in FM. Furthermore, MM constituted approximately a quarter of the total weight loss. Finally, our data support the use of less restrictive interventions, which appear to be more beneficial for BW and FM loss.

Energy Balance and Dietary Intake in Young Rugby Players during a Pre-Season Micro-Cycle: A Cluster Analysis.

Rugby players must develop excellent levels of conditioning during adolescence. However, this pivotal period of life is also characterized by a surge in biological growth, which further increases the energy and nutritional requirements of this population. This study examined within-individual differences in energy intake (EI) and energy balance (EB) of 46 young rugby players during a pre-season micro-cycle. Two clusters were identified with significantly different characteristics and EB states, suggesting that young rugby players adjust their EI to match their body composition goals. The first cluster is characterized by players with a low body fat% (12.87 ± 2.53). They had a positive EB (330 ± 517 kcal), suggesting a goal of increasing muscle mass. Conversely, the second cluster is characterized by a higher body fat% (23.1 ± 1.6, p < 0.005) and reported a negative, lower EB (-683 ± 425 kcal, p < 0.005), suggesting a goal focused on reducing fat mass. Although our study provides more optimistic results than previous ones regarding the high risk of inadequate EI in young rugby players, we emphasize the importance of rigorous nutritional support, especially for players aiming to lose weight, to avoid severe caloric restriction, as well as the downstream effects of such practices on their nutritional status, given the higher risk of macro- (e.g., CHO < 6 g/kg/d) and micronutrient (e.g., iron < 11 mg/d, calcium < 1300 mg/d, vitamin D < 5 mg/d) deficiencies.

Oral Drug Dosing After Gastric Bypass and Diet-Induced Weight Loss: Simpler Than We Think? Lessons Learned From the COCKTAIL Study.

This article summarizes the lessons learned from the COCKTAIL study: an open, three-armed, single-center study including patients with obesity scheduled for treatment with Roux-en-Y gastric bypass (RYGB) or nonsurgical calorie restriction, and a normal- to overweight control group. The clinical implications of the results from multiple peer-reviewed articles describing the effects of RYGB, severe caloric restriction, weight loss, and type 2 diabetes on the in vivo activity and protein expression of drug-metabolizing enzymes (cytochrome P450 (CYP) 1A2, 2C9, 2C19, and 3A) and transporters (DMETs; organic anion-transporting polypeptide (OATP) 1B1 and P-glycoprotein (P-gp)) are discussed in the perspective of three clinically relevant questions: (1) How should clinicians get the dose right in patients after RYGB? (2) Will drug disposition in patients with obesity be normalized after successful weight loss? (3) Are dose adjustments needed according to obesity and diabetes status? Overall, RYGB seems to have a lower impact on drug disposition than previously assumed, but clinicians should pay close attention to drugs with a narrow therapeutic range or where a high maximum drug concentration may be problematic. Whether obesity-related alterations of DMETs normalize with substantial weight loss depends on the DMET in question. Obesity and diabetes downregulate the in vivo activity of CYP2C19 and CYP3A (only obesity) but whether substrate drugs should be dose adjusted is also dependent on other factors that influence clearance, that is, liver blood flow and protein binding. Finally, we recommend frequent and individualized follow-up due to high inter- and intraindividual variability in these patients, particularly following RYGB.

Reduction in metabolic noise reveals rejuvenation following transient severe caloric restriction.

Among land vertebrates, the laying hen stands out due to its great reproductive efficiency: producing an egg daily all year long. This production rate makes the laying hen a special model animal to study the general process of reproduction and aging. One unique aspect of hens is their ability to undergo reproductive plasticity and to rejuvenate their reproductive tract during molting, a standard industrial feed restriction protocol for transiently pausing reproduction, followed by improved laying efficiency almost to peak production. Here we use longitudinal metabolomics, immunology, and physiological assays to show that molting promotes reproduction, compresses morbidity, and restores youthfulness when applied to old hens. We identified circulating metabolic biomarkers that quantitatively predict the reproduction and age of individuals. Lastly, we introduce metabolic noise, a robust, unitless, and quantifiable measure for heterogeneity of the complete metabolome as a general marker that can indicate the rate of aging of a population. Indeed, metabolic noise increased with age in control hens, whereas molted hens exhibited reduced noise following molting, indicating systemic rejuvenation. Our results suggest that metabolic noise can be used as a quick and universal proxy for assessing successful aging treatments, accelerating the timeline for drug development.

FRI315 Hyperprolactinemia In The Presence Of Severe Calorie Restriction And Stress

Abstract Disclosure: T. Alrasheed: None. M. Alanazi: None. L. Albishi: None. H. Mirghani: None. Abstract: The effects of obesity and calorie restriction on prolactin levels (PL) are controversial. Here, we have an unusual case of physiological hyperprolactinemia in the presence of severe calorie restriction and emotional stressors. Case Presentation A 31-year-old security guard with obesity (31.5 kg/m2) started dieting by adopting severe calorie restrictions at 900 calories a day. He lost about 15 kg in two months, but even with weight loss, he was in poor health. He felt fatigued and unable to work. On testing, he had an elevated PL of 78.93 ng/ml. The remaining tests were normal, however, with the elevated PL, he was referred to our endocrinology clinic. He had a negative medical, surgical, and family history. He had a normal physical exam. We increased his calorie intake gradually to ∼2000 calories/day. With these changes, his energy improved, and his symptoms were resolved. The repeated PL was normalized (14.70 ng/ml). Discussion In clinical practice, hyperprolactinemia can result from physiological, pharmacological, or pathological causes due to the widespread effect of prolactin on the body. One of the physiological causes is stress, which could raise PL to 100 ng/ml, although the exact mechanism needs further study. It has been suggested that physiological stress affects the neuroendocrine by inducing changes in dopamine and serotonin levels, contributing to the increase in PL. However, the relationship between PL and obesity is controversial. While there was no direct association between the two even after significant weight loss, (similarly, changes in calories did not show a direct effect on PL) there was a study that showed enhancement of prolactin release in obese women in proportion to the size of their visceral fat, and severe weight loss was associated with a reduction in PL. In our case, calorie restriction was the start of this cascade of symptoms and elevated PL. Decreased calorie intake affected his daily function, which led to his emotional stress, which in turn led to hyperprolactinemia. After increasing calorie consumption and resolving his physical stressors, his symptoms improved, and his PL was normalized. Conclusion A combination of low-calorie diets and stress could cause hyperprolactinemia. Further study is required to understand the clinical significance of elevated PL and its physiological functions. Knowing the widespread effect and relationship of prolactin in the body will help to avoid misdiagnoses and unnecessary treatments.

Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial.

Severe calorie restriction, in the form of cyclic fasting or fasting-mimicking diets (FMDs), boosts the antitumor activity of cytotoxic chemotherapy in mouse models of triple-negative breast cancer (TNBC). This effect is mostly mediated by fasting/FMD-induced reduction of plasma glucose concentration and by a boost in antitumor immunity. However, clinical evidence that cyclic FMD may impact on the outcomes of advanced TNBC (aTNBC) patients is lacking. We compared the overall survival (OS) of 14 aTNBC patients receiving first-line carboplatin-gemcitabine plus cyclic FMD in the context of the NCT03340935 trial with the OS of 76 consecutive aTNBC patients treated with carboplatin-based chemotherapy alone at Fondazione IRCCS Istituto Nazionale dei Tumori. Multivariable Cox regression models were used to adjust the prognostic impact of FMD for other prognostic variables. Patients undergoing cyclic FMD in combination with carboplatin-gemcitabine had better OS when compared to patients receiving chemotherapy alone (median OS 30.3 months, 95% CI 18-NR, vs 17.2 months, 95% CI 15.3-25.1, log-rank P value .041). Multivariable analysis confirmed an association between FMD use and better OS (HR: 0.40; 95% CI: 0.19-0.86; P = .019) also after propensity score-based matching according to patient ECOG PS and the presence of de novo metastatic disease (HR: 0.41; 95% CI: 0.21-0.83; P = .013). Cyclic FMD in combination with first-line chemotherapy may improve clinical outcomes in aTNBC patients. Our study paves the way for conducting phase II trials to investigate if cyclic FMD can increase the antitumor activity/efficacy of chemotherapy or chemoimmunotherapy in patients with early-stage TNBC or aTNBC.

Metal ion content of internal organs in the calorically restricted Wistar rat

BackgroundDespite the agreed principle that access to food is a human right, undernourishment and metal ion deficiencies are public health problems worldwide, exacerbated in impoverished or war-affected areas. It is known that maternal malnutrition causes growth retardation and affects behavioral and cognitive development of the newborn. Here we ask whether severe caloric restriction leads per se to disrupted metal accumulation in different organs of the Wistar rat. MethodsInductively coupled plasma optical emission spectroscopy was used to determine the concentration of multiple elements in the small and large intestine, heart, lung, liver, kidney, pancreas, spleen, brain, spinal cord, and three skeletal muscles from control and calorically restricted Wistar rats. The caloric restriction protocol was initiated from the mothers prior to mating and continued throughout gestation, lactation, and post-weaning up to sixty days of age. ResultsBoth sexes were analyzed but dimorphism was rare. The pancreas was the most affected organ presenting a higher concentration of all the elements analyzed. Copper concentration decreased in the kidney and increased in the liver. Each skeletal muscle responded to the treatment differentially: Extensor Digitorum Longus accumulated calcium and manganese, gastrocnemius decreased copper and manganese, whereas soleus decreased iron concentrations. Differences were also observed in the concentration of elements between organs independently of treatment: The soleus muscle presents a higher concentration of Zn compared to the other muscles and the rest of the organs. Notably, the spinal cord showed large accumulations of calcium and half the concentration of zinc compared to brain. X-ray fluorescence imaging suggests that the extra calcium is attributable to the presence of ossifications whereas the latter finding is attributable to the low abundance of zinc synapses in the spinal cord. ConclusionSevere caloric restriction did not lead to systemic metal deficiencies but caused instead specific metal responses in few organs.

Caloric restriction as a possible pitfall for persistent acromegaly follow-up – case report

BackgroundAcromegaly diagnosis is established when plasma levels of IGF-1 are increased and the Oral Glucose Tolerance Test (OGTT) with 75gr of glucose can’t suppress Growth Hormone (GH) levels. These two parameters are also useful during follow-up, after surgical/radiologic therapy and/or during medical therapy.Case presentationA 29-year-old woman was diagnosed with acromegaly after a severe headache. Previous amenorrhea and facial and acral changes were noticed. A pituitary macroadenoma was found, biochemical evaluation was in agreement with the suspected acromegaly and a transsphenoidal adenectomy was performed. As the disease recurred, a surgical reintervention and radiosurgery (Gamma Knife, 22 Gy) were necessary. No normalization of IGF-1 was achieved during three years after radiosurgery. Surprisingly, then, and although clinical features seemed getting worse, IGF-1 levels became consistently controlled to 0.3–0.8 times the upper limit of the reference range. Questioned, the patient referred that she was following an intermittent fasting dietary plan. However, based on the dietary questionnaire, she was found to be under severe caloric restriction. First OGTT (under caloric restriction) showed absence of GH suppression and an IGF-1 value of 234 ng/dL (Reference Range 76–286 ng/mL). A second OGTT, one month after an eucaloric diet was instituted, showed an increased IGF-1 of 294 ng/dL, maintaining an unsuppressed, yet less elevated, GH.ConclusionsGHRH/GH/IGF-1 axis controls somatic growth. Regulation is complex, and nutrition status and feeding pattern have a recognized role. Like systemic inflammation or chronic liver disease, fasting and malnutrition decrease the expression of hepatic GH receptors, with consequent reduction of IGF-1 levels, through resistance to GH. This clinical report shows that caloric restriction may represent a pitfall in acromegaly follow-up.

Dieting Behavior Characterized by Caloric Restriction and Relation to Sleep: A Brief Contemporary Review.

There is sufficient evidence showing that greater sleep quality improves weight loss outcomes achieved through dietary modifications; however, the effects of dietary modifications such as caloric restriction on sleep outcomes is less established. Caloric restriction is a commonly recommended weight-loss method, yet it may result in short-term weight loss and subsequent weight regain, known as "weight cycling", which has recently been shown to be associated with both poor sleep and worse cardiovascular health. The purpose of this brief narrative review was to summarize the evidence from recent studies of the effects of caloric restriction on sleep. Six articles were identified that specifically measured effects of a caloric restriction-based intervention on aspects of sleep as primary or secondary outcomes. Most research to date indicates that caloric restriction improves sleep outcomes including sleep quality and sleep onset latency. However, the relation between caloric restriction and sleep duration is less clear. Given the mixed results and the potential for severe caloric restriction to lead to weight cycling, future studies are needed to clarify how caloric restriction affects sleep and the potential implications for weight-management efforts.

Nutrition Interventions for Weight Gain and Body Composition Changes in Menopausal Women: A Review

ObjectivesDuring menopause many women experience weight gain and significant changes in body composition, including increase in visceral adipose tissue (VAT). Obesity and increased fat mass are both associated with comorbidities such as cardiovascular disease, which is the leading cause of death in postmenopausal women. Dietary interventions can address weight and body composition changes; however, few studies have researched nutrition interventions for this population. The aim of this review is to compare the effects of hypocaloric diets and the Mediterranean Diet (MD) on menopausal weight gain and body composition changes.MethodsA literature search was conducted using Pubmed, Google Scholar, and reference hand searching. Screening included hypocaloric diets (including intermittent fasting) and MD interventions for peri and post-menopausal women. Studies excluded were studies that combined diet and exercise interventions without a separate nutrition intervention, nutrition interventions based solely on a micronutrient, studies that included premenopausal participants (unless as a comparator), and outcomes that did not include weight and/or body composition. Of the 51 screened articles, 7 matched the inclusion criteria.ResultsFour of the 7 studies were randomized controlled trials (RCTs), two were cross-sectional studies, and one was a quasi-experimental study. All experimental studies found both hypocaloric diets and the MD may decrease weight and VAT. The two cross-sectional studies showed associations between lower BMI and VAT with increased adherence to the MD. One study found that severe caloric restriction may be associated with bone density loss. The studies differed in the classification of menopausal stages.ConclusionsThese findings suggest both hypocaloric diets and the MD may reduce body weight and decrease VAT in peri and post-menopausal women. However, there are few studies addressing nutrition interventions for this population. More high quality studies are needed to examine these important menopausal changes and nutrition interventions.Funding SourcesNone.

The role of CD36-Fabp4-PPAR\u03b3 in skeletal muscle involves insulin resistance in intrauterine growth retardation mice with catch-up growth

BackgroundStudies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society.MethodsThe pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes.ResultsAfter dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05).ConclusionsLBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways.

Anemic retinopathy as a presenting feature of severe dimorphic nutritional anemia in a young male patient after crash dieting

We report the case of a 31-year-old male patient who presented for a routine ophthalmological examination. Evaluation revealed the presence of bilateral flame-shaped hemorrhages and Roth's spots. Hematological evaluation revealed the presence of severe iron deficiency anemia with megaloblastic anemia. This case documents the occurrence of anemic retinopathy in dimorphic nutritional anemia after crash dieting (severe calorie restriction).

Leptin treatment prevents impaired hypoglycemic counterregulation induced by exposure to severe caloric restriction or exposure to recurrent hypoglycemia.

Hypoglycemia-associated autonomic failure (HAAF) is a maladaptive failure in glucose counterregulation in persons with diabetes (PWD) that is caused by recurrent exposure to hypoglycemia. The adipokine leptin is known to regulate glucose homeostasis, and leptin levels fall following exposure to recurrent hypoglycemia. Yet, little is known regarding how reduced leptin levels influence glucose counterregulation, or if low leptin levels are involved in the development of HAAF. The purpose of this study was to determine the effect of hypoleptinemia on the neuroendocrine responses to hypoglycemia. We utilized two separate experimental paradigms known to induce a hypoleptinemic state: 60% caloric restriction (CR) in mice and three days of recurrent hypoglycemia (3dRH) in rats. A sub-set of animals were also treated with leptin (0.5-1.0μg/g) during the CR or 3dRH periods. Neuroendocrine responses to hypoglycemia were assessed 60min following an IP insulin injection on the terminal day of the paradigms. CR mice displayed defects in hypoglycemic counterregulation, indicated by significantly lower glucagon levels relative to controls, 13.5pmol/L (SD 10.7) versus 64.7pmol/L (SD 45) (p=0.002). 3dRH rats displayed reduced epinephrine levels relative to controls, 1900pg/mL (SD 1052) versus 3670pg/mL (SD 780) (p=0.030). Remarkably, leptin treatment during either paradigm completely reversed this effect by normalizing glucagon levels in CR mice, 78.0pmol/L (SD 47.3) (p=0.764), and epinephrine levels in 3dRH rats, 2910pg/mL (SD 1680) (p=0.522). These findings suggest that hypoleptinemia may be a key signaling event driving the development of HAAF and that leptin treatment may prevent the development of HAAF in PWD.

Abstract P138: Long-term Effects Of Severe Caloric Restriction To The Heart Function

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received ad libitum chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p&lt;0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p&lt;0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet ( data not shown ) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.

Does caloric restriction prime the microbiome for pathogenic bacteria?

A recent study in Nature finds significant shifts in the gut microbiome of post-menopausal women on severe calorie restriction concomitant with weight loss. Microbiota transplantation to germ-free mice display a similar weight loss, along with a bloom in C.difficile, unlocking clues to microbial metabolic alteration in weight loss.

The ‘bald’ phenotype (androgenetic alopecia) is caused by the high glycaemic, high cholesterol and low mineral ‘western diet’

BackgroundThe success of 5α-reductase inhibitors in the 1990s vindicated the role of androgens and cast doubt on the role of diet in androgenetic alopecia (AGA). However, poor glucose control and high cholesterol are now recognised as comorbidities, which are salient characters of the ‘western diet’. Scope and approachIn glucose potentiated hair loss, continuous monosaccharide flux to the liver promotes the polyol pathway, causing fatty liver and attenuating synthesis of sex hormone binding globulin, accommodating the increased ratio of dihydrotestosterone (DHT) to testosterone. The scalp of the balding phenotype is characterised by overactive PPAR-γ receptors, increased fatty acid synthesis, enlarged sebaceous glands and sebum secretions. Sebum feeds lipophilic bacteria, such as Propionibacterium acnes, which augment the expression of prostaglandin-type (PGD2 & 15d-PGJ2) ligands of PPAR-γ and increase local insulin sensitivity via Akt/mTOR pathways. In hyperglycaemic events the androgen dependent polyol pathway depletes glucose and generates purine by-products that antagonise adenosine receptors. Mitochondrial reactive oxygen species accumulate, and ATP levels reduce, slowing gluconeogenesis in the outer root sheath keratinocytes of the hair follicle. Furthermore, the current commentary suggests that an important mineral in hair health is magnesium, which is relevant to both glucose and cholesterol potentiated hair loss. Magnesium deficiency not only reinforces insulin resistance, but in cholesterol potentiated hair loss, local magnesium dependent monooxygenase enzymes that metabolise cholesterol and vitamin D are impaired. Furthermore, magnesium deficient muscles at the occipital and temporal region of the skull create mechanical strain against the galea aponeurotica. Key findings and conclusionsTaking all of this into consideration, treatment options for androgenetic alopecia should include a low cholesterol and low glycaemic index diet, improved glucose control, and fortification with magnesium. Furthermore, the current narrative does not endorse severe caloric restriction for obvious health reasons.

Caloric restriction disrupts the microbiota and colonization resistance.

Diet is a major factor that shapes the gut microbiome1, but the consequences of diet-induced changes in the microbiome for host pathophysiology remain poorly understood. We conducted a randomized human intervention study using a very-low-calorie diet (NCT01105143). Although metabolic health was improved, severe calorie restriction led to a decrease in bacterial abundance and restructuring of the gut microbiome. Transplantation of post-diet microbiota to mice decreased their body weight and adiposity relative to mice that received pre-diet microbiota. Weight loss was associated with impaired nutrient absorption and enrichment in Clostridioides difficile, which was consistent with a decrease in bile acids and was sufficient to replicate metabolic phenotypes in mice in a toxin-dependent manner. These results emphasize the importance of diet-microbiome interactions in modulating host energy balance and the need to understand the role of diet in the interplay between pathogenic and beneficial symbionts.

Progression of anorexia nervosa: An insight into neurological and biological mechanisms influencing the personality patterns of anorexics

Anorexia nervosa has emerged as a prominent eating disorder affecting young women. This disorder's fundamental characteristic is an abnormally low weight achieved by severe calorie restriction and refusal to maintain body weight at or above the minimally normal weight for age and height. It is a complex disorder with its origins still not explicitly defined. In anorexic individuals, an imbalance in the molecular signalling and hypothalamic neuropeptides is believed to be significantly responsible for alterations in the biological mechanisms associated with body weight, appetite and energy homeostasis. The imbalance between the genetic systems such as serotonin, dopamine, brain-derived neurotrophic factor, estrogen and their interactions are significantly observed in anorexic as well as recovered anorexic individuals. The dopaminergic pathway is involved in reward mechanisms but its dysfunction might cause weight loss, food aversion, hyperactivity, obsessive compulsive behaviours, distorted body image. An abnormal serotonin function reveals personality traits such as rigidity, inhibition, anxiety, inflexibility, perfectionism and harm avoidance. The Met66 variant of brain derived neurotrophic factor is strongly associated with the development of restricting-type anorexia nervosa. The development of anorexia has been linked to estrogen receptor beta gene variants, which also regulate food intake and states of anxiety and depression.This review discusses the neurobiological dysregulations because of which anorexics tend to have a distinct personality profile characterized by behaviour patterns comprising perfectionism, obsessive-compulsive disorder, harm avoidance, alexithymia, anger suppression, anxiety, rigidity, novelty seeking, anhedonia, depression, impulsivity, substance abuse, self harm etc. Heterogeneities in the characteristic profile are observed based on the subdivisions of anorexia nervosa. The impact of malnutrition has also been scrutinized.

Cardioprotective effects of severe calorie restriction from birth in adult ovariectomized rats

AimsMenopause is a female condition induced by a reduction of ovarian hormone and is related to an increase in cardiovascular diseases in women. We have shown that severe calorie restriction (SCR) from birth reduces the cardiometabolic risk in adult male Wistar rats. In this study, we investigated the effects of SCR from birth to adulthood on cardiovascular function of ovariectomized rats. Main methodsFrom birth to adulthood, rats were daily fed ad libitum (control group - C) or with 50% of the amount consumed by the control group (calorie-restricted group - R). At 90 days, half of the rats in each group underwent bilateral ovariectomy (OVX), totaling 4 groups: C-Sham, C-OVX, R-Sham, R-OVX. Systolic blood pressure (SBP), heart rate (HR) and, double product (DP) index were recorded by tail-cuff plethysmography. Cardiac function was analyzed by the Langendorff technique and cardiomyocyte diameter was accessed by histologic analysis. Additionally, cardiac SERCA2 content and redox status were evaluated. Key findingsC-OVX rats exhibited reduced cardiac function and cardiac non-enzymatic total antioxidant capacity (TAC). R-Sham animals showed reduced SBP, DP, HR, improved cardiac function, reduced cardiac protein carbonyl derivatives and increased TAC, catalase, and superoxide dismutase activities. R-OVX rats maintained reduced SBP, DP, HR, and increased contractility and relaxation indexes. R-Sham and R-OVX rats exhibited preserved heart mass and reduced cardiomyocyte diameter. Cardiac SERCA2 content did not differ between the groups. SignificanceTaken together, our findings show cardioprotective effects of SCR from birth in adult ovariectomized rats.