Investigating the Health Implications of Whey Protein Consumption: A Narrative Review of Risks, Adverse Effects, and Associated Health Issues.

This narrative review critically examines the current research on the health implications of whey protein (WP) supplementation, with a focus on potential risks and adverse effects. WP, commonly consumed for muscle building and weight loss, has been associated with various health concerns. Our comprehensive analysis involved a thorough search of multiple databases, resulting in the inclusion of 21 preclinical and human studies that collectively offer a detailed overview of WP's health impacts. The review reveals significant findings, such as WP's potential link to liver and kidney damage, alterations in gut microbiota, increased acne incidence, impacts on bone mass, and emotional and behavioural changes. These findings underscore the complexity of WP's effects on human health, indicating both beneficial and detrimental outcomes in relation to different posologies in a variety of settings. Our study suggests caution for the protein intake in situations of hepatic and renal compromised functions, as well as in acne susceptibility, while possible beneficial effects can be achieved for the intestinal microbiota, humoral and behavioural level, and finally bone and muscle mass in elderly. We emphasizes the importance of balanced WP consumption and call for more in-depth research to understand its long-term health effects. Health professionals and individuals considering WP supplementation should be aware of these potential risks and approach its use with informed caution.

Weight Management Effectiveness and Predictors of Dropout in Breast Cancer Survivors: A Retrospective Study.

BACKGROUND: Reducing obesity and weight gain, which often occurs during breast cancer treatment, may represent an efficient secondary or tertiary prevention against cancer. PURPOSE: This retrospective observational cohort study aimed to assess the impact of a Mediterranean diet on weight and anthropometric changes in women completing active breast cancer treatment. Additionally, we sought to identify factors associated with study dropout within one year. METHODS: A total of 182 female patients (20 normal weight, 59 overweight, 103 obese) received personalized Mediterranean diet interventions and underwent monthly outpatient visits. RESULTS: Dropout rates were 42.3% at 6 months and 64.1% at 12 months. Among the obese subgroup, BMI (p < 0.001) and fat mass (p < 0.05) decreased after 6 months. At 12 months, the obese subgroup showed a borderline significant further reduction in BMI (p = 0.062). BMI or weight loss did not predict dropout at any time point. However, age (OR = 0.91) and diastolic blood pressure (OR = 1.07) were significant predictors of dropout at 12 months. CONCLUSION: Implementing a Mediterranean diet can lead to weight and anthropometric improvements in breast cancer survivors. Further research is necessary to explore the long-term effects of weight loss on these individuals, identify effective dietary approaches, and consider specific predictors of dropout.

Long-term intensive endurance exercise training is associated to reduced markers of cellular senescence in the colon mucosa of older adults.

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence-a state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly higher in the colon mucosa of middle-aged and older overweight adults than in young sedentary individuals, but this upregulation was significantly blunted in age-matched endurance runners. Interestingly, we observe a linear correlation between the level of p16 and the triglycerides to HDL ratio, a marker of colon adenoma risk and cardiometabolic dysfunction. Our data suggest that chronic high-volume high-intensity endurance exercise can play a role in preventing the accumulation of senescent cells in cancer-prone tissues like colon mucosa with age. Future studies are warranted to elucidate if other tissues are also affected, and what are the molecular and cellular mechanisms that mediate the senopreventative effects of different forms of exercise training.

Breast Cancer Diet "BCD": A Review of Healthy Dietary Patterns to Prevent Breast Cancer Recurrence and Reduce Mortality.

Breast cancer (BC) represents the most common cancer in women, while overweight and obesity are the second preventable cause of cancer. Weight gain and fat accumulation are common after BC diagnosis; moreover, weight gain during the treatment decreases the survival rate and increases the risk of recurrence in breast cancer survivors (BCS). To reduce the risk of second primary cancer or BC recurrence, and all-cause mortality in BCS, multiple interventions have been investigated to obtain reduction in weight, BMI and/or waist circumference. The aim of this narrative review is to analyze evidence on BCS for their risk of recurrence or mortality related to increased weight or fat deposition, and the effects of interventions with healthy dietary patterns to achieve a proper weight and to reduce fat-related risk. The primary focus was on dietary patterns instead of single nutrients and supplements, as the purpose was to investigate on secondary prevention in women free from disease at the end of their cancer treatment. In addition, BC relation with insulin resistance, dietary carbohydrate, and glycemic index/glycemic load is discussed. In conclusion, obesity and overweight, low rates of physical activity, and hormone receptor-status are associated with poorer BC-treatment outcomes. To date, there is a lack of evidence to suggest which dietary pattern is the best approach for weight management in BCS. In the future, multimodal lifestyle interventions with dietary, physical activity and psychological support after BC diagnosis should be studied with the aim of reducing the risk of BC recurrence or mortality.

Obesity pandemic during COVID-19 outbreak: Narrative review and future considerations.

The high prevalence of obesity and obesity-related comorbidities has reached pandemic proportions, particularly in Western countries. Obesity increases the risk to develop several chronic noncommunicable disease, ultimately contributing to reduced survival. Recently, obesity has been recognized as major risk factor for coronavirus disease-19 (COVID-19)-related prognosis, contributing to worse outcomes in those with established COVID-19. Particularly, obesity has been associated with higher hospitalization rates in acute or intensive care and greater risk for invasive mechanical ventilation than lean people. Obesity is characterized by metabolic impairments and chronic low-grade systemic inflammation that causes a pro-inflammatory microenvironment, further aggravating the cytokine production and risk of cytokine storm response during Sars-Cov2 sepsis or other secondary infections. Moreover, the metabolic dysregulations are closely related to an impaired immune system and altered response to viral infection that can ultimately lead to a greater susceptibility to infections, longer viral shedding and greater duration of illness and severity of the disease. In individuals with obesity, maintaining a healthy diet, remaining physically active and reducing sedentary behaviors are particularly important during COVID-19-related quarantine to reduce metabolic and immune impairments. Moreover, such stategies are of utmost importance to reduce the risk for sarcopenia and sarcopenic obesity, and to prevent a reduction and potentially even increase cardiorespiratory fitness, a well-known independent risk factor for cardiovascular and metabolic diseases and recently found to be a risk factor also for hospitalizations secondary to COVID-19. Such lifestyle strategies may ultimately reduce morbility and mortality in patients with infectious disease, especially in those with concomitant obesity. The aim of this review is to discuss how obesity might increase the risk of COVID-19 and potentially affect its prognosis once COVID-19 is diagnosed. We therefore advocate for implementation of strategies aimed at preventing obesity in the first place, but also to minimize the metabolic anomalies that may lead to a compromized immune response and chronic low-grade systemic inflammation, especially in patients with COVID-19.

Coronavirus disease 2019 pandemic and alterations of body composition.

PURPOSE OF REVIEW: This manuscript reviews evidence collected during COVID-19 pandemic and provides information on the impact of body composition on severity and outcomes of the disease, analysing methods used for body composition assessment. Malnutrition-screening tools will also be discussed to screen and diagnose the patients at higher risk of COVID-19 severity and related worse outcomes. RECENT FINDINGS: COVID-19 can occur in a wide range of presentation, from asymptomatic to severe forms. Among the major risk factors for worse severity, overnutrition, undernutrition and body composition play a role in the ability to respond to SARS-CoV-2 infection. Excess fat accumulation (i.e. obesity) or lean mass loss and functionality (i.e. sarcopenia) or a combination of both (i.e. sarcopenic obesity) can affect whole-body functioning. These body composition alterations in the short-term can influence susceptibility and immunological responses to the virus, inflammatory reaction, metabolic and respiratory distress, while in the long-term can modulate disease outcomes, namely length of stay, time required for recovery, risk of ICU-acquired weakness and long-term disabilities, and potentially increase the risk of death. SUMMARY: Individuals with malnutrition, sarcopenia, obesity, sarcopenic obesity and older adults with abnormal body composition or malnutrition risk may require tailored medical nutrition therapy to improve short and long-term COVID-19 outcomes.

Nutritional management of celiac crisis in an elderly adult: A case report of the rare presentation of celiac disease in a 75-y-old woman.

In adults, a very uncommon presentation of celiac disease (CD) is a celiac crisis, a life-threatening and severe form of the disease having a dramatic onset with diarrhea and metabolic acidosis with electrolyte and fluid imbalance. Treatment of celiac crisis requires a gluten-free diet; however, the risk for refeeding syndrome (RFS) should be considered in patients showing marked malabsorption symptoms and important unintentional weight loss. Therefore, to avoid metabolic and potentially fatal complications of re-nutrition, nutritional management is crucial for a safe recovery after a celiac crisis. This review reports the rare onset of celiac crisis in a 75-y-old woman presenting with severe malnutrition resulting in >40% weight loss in 3 mo, after a period of severe diarrhea and vomiting. She arrived at the hospital showing electrolyte imbalance, hypoalbuminemia, lower limb edema, multiple bowel movements (>10/d) with steatorrhea, sarcopenia with profound asthenia, hyporexia due to intolerance to any food, and vomiting after meals. After being diagnosed with CD, the first approach was a gluten-free diet, which demonstrated only small and slow improvements of gastrointestinal symptoms. Therefore, a second approach was parenteral nutrition (PN) support that dramatically helped the patient's recovery. Here we describe the nutritional management during the inpatient stay for clinical stabilization and the following outpatient visits during and after the support with PN, until the patient's complete recovery to a regular follow-up.

Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial.

The aim of the current study (Clinical trial reg. no. NCT02715193, clinicaltrials.gov) was to study the efficacy and safety of REMD-477, a glucagon receptor antagonist, in type 1 diabetes. This was a randomized controlled trial in which 21 patients with type 1 diabetes were enrolled. Glycaemic control and insulin use were evaluated in outpatient and inpatient settings, before and after a single 70-mg dose of REMD-477 (half-life 7-10 days) or placebo. Inpatient insulin use was 26% (95% CI, 47%, 4%) lower 1 day after dosing with REMD-477 than with placebo (P = .02). Continuous glucose monitoring during post-treatment days 6 to 12 showed that average daily glucose was 27 mg/dL lower (P < .001), percent time-in-target-range (70-180 mg/dL) was ~25% greater (~3.5 h/d) (P = .001), and percent time-in-hyperglycaemic-range (> 180 mg/dL) was ~40% lower (~4 h/d) (P = .001) in the REMD-477 group than in the placebo group, without a difference in percent time-in-hypoglycaemic-range (<70 mg/dL). No serious adverse events were reported. Glucagon receptor antagonism decreases insulin requirements and improves glycaemic control in patients with type 1 diabetes.

In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles.

Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age-associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied plasma samples from men with prostate cancer awaiting prostatectomy who participated in a randomized trial of one month of PR or control diet. We found increased levels of leptin receptor in the PR group in total plasma EVs and in a subpopulation of plasma EVs expressing the neuronal marker L1CAM. Protein restriction also shifted the phosphorylation status of the insulin receptor signal transducer protein IRS1 in L1CAM+ EVs in a manner suggestive of improved insulin sensitivity. Dietary PR modifies indicators of leptin and insulin signaling in circulating EVs. These findings are consistent with improved insulin and leptin sensitivity in response to PR and open a new window for following physiologic responses to dietary interventions in humans.

Preserving Healthy Muscle during Weight Loss.

Weight loss is the cornerstone of therapy for people with obesity because it can ameliorate or completely resolve the metabolic risk factors for diabetes, coronary artery disease, and obesity-associated cancers. The potential health benefits of diet-induced weight loss are thought to be compromised by the weight-loss-associated loss of lean body mass, which could increase the risk of sarcopenia (low muscle mass and impaired muscle function). The objective of this review is to provide an overview of what is known about weight-loss-induced muscle loss and its implications for overall physical function (e.g., ability to lift items, walk, and climb stairs). The currently available data in the literature show the following: 1) compared with persons with normal weight, those with obesity have more muscle mass but poor muscle quality; 2) diet-induced weight loss reduces muscle mass without adversely affecting muscle strength; 3) weight loss improves global physical function, most likely because of reduced fat mass; 4) high protein intake helps preserve lean body and muscle mass during weight loss but does not improve muscle strength and could have adverse effects on metabolic function; 5) both endurance- and resistance-type exercise help preserve muscle mass during weight loss, and resistance-type exercise also improves muscle strength. We therefore conclude that weight-loss therapy, including a hypocaloric diet with adequate (but not excessive) protein intake and increased physical activity (particularly resistance-type exercise), should be promoted to maintain muscle mass and improve muscle strength and physical function in persons with obesity.

Extra virgin olive oil improves post-prandial glycemic and lipid profile in patients with impaired fasting glucose.

BACKGROUND & AIMS: Extra virgin olive oil (EVOO) improves post-prandial glycaemia in healthy subjects but it has never been investigated if this can be detected in pre-diabetic patients. We investigated if EVOO affects post-prandial glucose and lipid profile in patients with impaired fasting glucose (IFG). METHODS: Thirty IFG patients were randomly allocated to a meal containing or not 10 g of EVOO in a cross-over design. Before, 60 min and 120 min after lunch a blood sample was taken to measure glucose, insulin, Glucagon-like peptide-1 (GLP1), dipeptidyl-peptidase-4 (DPP4) activity, triglycerides (TG), total cholesterol, HDL-cholesterol and Apo B-48. RESULTS: The meal containing EVOO was associated with a reduction of glucose (p = 0.009) and DPP4 activity (p < 0.001) and a significant increase of insulin (p < 0.001) and GLP-1 (p < 0.001) compared with the meal without EVOO. Furthermore, the meal containing EVOO showed a significant decrease of triglycerides (p = 0.002) and Apo B-48 (p = 0.002) compared with the meal without EVOO. Total cholesterol and HDL cholesterol levels did not significantly change between the two groups. CONCLUSIONS: This is the first study to show that in IFG patients EVOO improves post-prandial glucose and lipid profile with a mechanism probably related to incretin up-regulation.

Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health.

Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.

Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle.

Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3-15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles.

Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model.

Reduced dietary protein intake and intermittent fasting (IF) are both linked to healthy longevity in rodents, and are effective in inhibiting cancer growth. The molecular mechanisms underlying the beneficial effects of chronic protein restriction (PR) and IF are unclear, but may be mediated in part by a down-regulation of the IGF/mTOR pathway. In this study we compared the effects of PR and IF on tumor growth in a xenograft mouse model of breast cancer. We also investigated the effects of PR and IF on the mechanistic Target Of Rapamycin (mTOR) pathway, inhibition of which extends lifespan in model organisms including mice. The mTOR protein kinase is found in two distinct complexes, of which mTOR complex 1 (mTORC1) is responsive to acute treatment with amino acids in cell culture and in vivo. We found that both PR and IF inhibit tumor growth and mTORC1 phosphorylation in tumor xenografts. In somatic tissues, we found that PR, but not IF, selectively inhibits the activity of the amino acid sensitive mTORC1, while the activity of the second mTOR complex, mTORC2, was relatively unaffected by PR. In contrast, IF resulted in increased S6 phosphorylation in multiple metabolic tissues. Our work represents the first finding that PR may reduce mTORC1 activity in tumors and multiple somatic tissues, and suggest that PR may represent a highly translatable option for the treatment not only of cancer, but also other age-related diseases.

Will calorie restriction work in humans?

Calorie Restriction (CR) without malnutrition slows aging and increases average and maximal lifespan in simple model organisms and rodents. In rhesus monkeys long-term CR reduces the incidence of type 2 diabetes, cardiovascular disease and cancer, and protects against age-associated sarcopenia and neurodegeneration. However, so far CR significantly increased average lifespan only in the Wisconsin, but not in the NIA monkey study. Differences in diet composition and study design between the 2 on-going trials may explain the discrepancies in survival and disease. Nevertheless, many of the metabolic and hormonal adaptations that are typical of the long-lived CR rodents did not occur in either the NIA or WNPRC CR monkeys. Whether or not CR will extend lifespan in humans is not yet known, but accumulating data indicate that moderate CR with adequate nutrition has a powerful protective effect against obesity, type 2 diabetes, inflammation, hypertension, cardiovascular disease and reduces metabolic risk factors associated with cancer. Moreover, CR in human beings improves markers of cardiovascular aging, and rejuvenates the skeletal muscle transcriptional profile. More studies are needed to understand the interactions between CR, diet composition, exercise, and other environmental and psychological factors on metabolic and molecular pathways that regulate health and longevity.

Lower-limb joint coordination pattern in obese subjects.

The coordinative pattern is an important feature of locomotion that has been studied in a number of pathologies. It has been observed that adaptive changes in coordination patterns are due to both external and internal constraints. Obesity is characterized by the presence of excess mass at pelvis and lower-limb areas, causing mechanical constraints that central nervous system could manage modifying the physiological interjoint coupling relationships. Since an altered coordination pattern may induce joint diseases and falls risk, the aim of this study was to analyze whether and how coordination during walking is affected by obesity. We evaluated interjoint coordination during walking in 25 obese subjects as well as in a control group. The time-distance parameters and joint kinematics were also measured. When compared with the control group, obese people displayed a substantial similarity in joint kinematic parameters and some differences in the time-distance and in the coupling parameters. Obese subjects revealed higher values in stride-to-stride intrasubjects variability in interjoint coupling parameters, whereas the coordinative mean pattern was unaltered. The increased variability in the coupling parameters is associated with an increased risk of falls and thus should be taken into account when designing treatments aimed at restoring a normal locomotion pattern.

Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months' consumption of a combination of bioactive food ingredients in overweight subjects.

This randomized, double blind, placebo-controlled, 8 week trial assessed the efficacy on metabolic changes produced by a consumption of a combination of bioactive food ingredients (epigallocatechin gallate, capsaicins, piperine and L-carnitine) versus a placebo, as part of a therapeutic 'lifestyle change' diet, in 86 overweight subjects. Forty-one patients (2/14 F/M; age 43.7 ± 8.5; BMI 30.3 ± 3.5 kg/m(2)) were randomized to the supplemented group and 45 (29/16; age 40.7 ± 10.2; BMI 30.0 ± 2.7) to the control group. We observed that consumption of the dietary supplement was associated with a significantly greater decrease in insulin resistance, assessed by homostasis model assessment (p < 0.001), leptin/adiponectin ratio (p < 0.04), respiratory quotient (p < 0.008). LDL-cholesterol levels (p < 0.01). Moreover, statistically significant differences were recorded between the two groups in relation to urinary norepinephrine levels (p < 0.001). Leptin, ghrelin, C-reactive protein decreased and resting energy expenditure increased significantly in the supplemented group (p < 0.05, 0.03, 0.02 and 0,02 respectively), but not in the placebo group; adiponectin decreased significantly in the placebo group (0.001) but not in the supplemented group, although no statistical significance between the groups was elicited. BMI, fat mass (assessed by DXA) and vascular endothelial growth factor significantly decreased, whilst the resting energy expenditure/free fat mass significantly increased in both groups. In general, a greater change was recorded in the supplemented group compared to the placebo, although no statistically significant difference between the two groups was recorded. These results suggest that the combination of bioactive food ingredients studied might be useful for the treatment of obesity-related inflammatory metabolic dysfunctions.