Polycystic Kidney Disease Diet: What is Known and What is Safe.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by kidney cyst formation and progressive kidney function loss. Dietary interventions such as caloric restriction, intermittent fasting, and ketogenic diet have recently emerged as potential strategies to induce metabolic reprogramming and slow ADPKD progression. We review the available evidence supporting the efficacy and safety of these interventions in ADPKD. Dietary interventions show promise in managing ADPKD by improving metabolic health and reducing oxidative stress. However, while preclinical studies have shown favorable outcomes, limited clinical evidence supports their effectiveness. In addition, the long-term consequences of these dietary interventions, including their effect on adverse events in patients with ADPKD, remain uncertain. To optimize ADPKD management, patients are advised to follow a dietary regimen that aims to achieve or maintain an ideal body weight and includes high fluid intake, low sodium, and limited concentrated sweets. Caloric restriction seems particularly beneficial for patients with overweight or obesity because it promotes weight loss and improves metabolic parameters. Supplementation with curcumin, ginkgolide B, saponins, vitamin E, niacinamide, or triptolide has demonstrated uncertain clinical benefit in patients with ADPKD. Notably, ß -hydroxybutyrate supplements have shown promise in animal models; however, their safety and efficacy in ADPKD require further evaluation through well-designed clinical trials. Therefore, the use of these supplements is not currently recommended for patients with ADPKD. In summary, dietary interventions such as caloric restriction, intermittent fasting, and ketogenic diet hold promise in ADPKD management by enhancing metabolic health. However, extensive clinical research is necessary to establish their effectiveness and long-term effects. Adhering to personalized dietary guidelines, including weight management and specific nutritional restrictions, can contribute to optimal ADPKD management. Future research should prioritize well-designed clinical trials to determine the benefits and safety of dietary interventions and supplementation in ADPKD.

The Microbiome, Epigenome, and Diet in Adults with Obesity during Behavioral Weight Loss.

Obesity has been linked to the gut microbiome, epigenome, and diet, yet these factors have not been studied together during obesity treatment. Our objective was to evaluate associations among gut microbiota (MB), DNA methylation (DNAme), and diet prior to and during a behavioral weight loss intervention. Adults (n = 47, age 40.9 ± 9.7 years, body mass index (BMI) 33.5 ± 4.5 kg/m2, 77% female) with data collected at baseline (BL) and 3 months (3 m) were included. Fecal MB was assessed via 16S sequencing and whole blood DNAme via the Infinium EPIC array. Food group and nutrient intakes and Healthy Eating Index (HEI) scores were calculated from 7-day diet records. Linear models were used to test for the effect of taxa relative abundance on DNAme and diet cross-sectionally at each time point, adjusting for confounders and a false discovery rate of 5%. Mean weight loss was 6.2 ± 3.9% at 3 m. At BL, one MB taxon, Ruminiclostridium, was associated with DNAme of the genes COL20A1 (r = 0.651, p = 0.029), COL18A1 (r = 0.578, p = 0.044), and NT5E (r = 0.365, p = 0.043). At 3 m, there were 14 unique MB:DNAme associations, such as Akkermansia with DNAme of GUSB (r = -0.585, p = 0.003), CRYL1 (r = -0.419, p = 0.007), C9 (r = -0.439, p = 0.019), and GMDS (r = -0.559, p = 0.046). Among taxa associated with DNAme, no significant relationships were seen with dietary intakes of relevant nutrients, food groups, or HEI scores. Our findings indicate that microbes linked to mucin degradation, short-chain fatty acid production, and body weight are associated with DNAme of phenotypically relevant genes. These relationships offer an initial understanding of the possible routes by which alterations in gut MB may influence metabolism during weight loss.

Proteomics, dietary intake, and changes in cardiometabolic health within a behavioral weight-loss intervention: A pilot study.

OBJECTIVE: Identifying associations among circulating proteins, dietary intakes, and clinically relevant indicators of cardiometabolic health during weight loss may elucidate biologically relevant pathways affected by diet, allowing for an incorporation of precision nutrition approaches when designing future interventions. This study hypothesized that plasma proteins would be associated with diet and cardiometabolic health indicators within a behavioral weight-loss intervention. METHODS: This secondary data analysis included participants (n = 20, mean [SD], age: 40.1 [9.5] years, BMI: 34.2 [4.0] kg/m2 ) who completed a 1-year behavioral weight-loss intervention. Cardiovascular disease-related plasma proteins, diet, and cardiometabolic health indicators were evaluated at baseline and 3 months. Associations were determined via linear regression and integrated networks created using Visualization Of LineAr Regression Elements (VOLARE). RESULTS: A total of 16 plasma proteins were associated with ≥1 diet or health indicator at baseline (p < 0.001); changes in 42 proteins were associated with changes in diet or health indicators from baseline to 3 months (p < 0.005). Baseline tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) was associated with intakes of dark green vegetables (r = -0.712), and fatty acid-binding protein 4 (FABP4) was associated with intakes of unsweetened coffee (r = -0.689). Changes in refined-grain intakes were associated with changes in scavenger receptor cysteine-rich type 1 protein M130 (CD163; r = 0.725), interleukin-1 receptor type 1 (IL1R-T1; r = 0.624), insulin (r = 0.656), and triglycerides (r = 0.648). CONCLUSIONS: Circulating cardiovascular disease-related proteins were associated with diet and cardiometabolic health indicators prior to and in response to weight loss.

Comparison of weight loss induced by daily caloric restriction versus intermittent fasting (DRIFT) in individuals with obesity: study protocol for a 52-week randomized clinical trial.

BACKGROUND: The standard of care for treating overweight and obesity is daily caloric restriction (DCR). While this approach produces modest weight loss, adherence to DCR declines over time and weight regain is common. Intermittent fasting (IMF) is an alternative dietary strategy for reducing energy intake (EI) that involves >60% energy restriction on 2-3 days per week, or on alternate days, with habitual intake on fed days. While numerous studies have evaluated IMF as a weight loss strategy, there are several limitations including lack of a standard-of-care DCR control, failure to provide guideline-based behavioral support, and failure to rigorously evaluate dietary and PA adherence using objective measures. To date, only three longer-term (52-week) trials have evaluated IMF as a weight loss strategy. None of these longer-duration studies reported significant differences between IMF and DCR in changes in weight. However, each of these studies has limitations that prohibit drawing generalizable conclusions about the relative long-term efficacy of IMF vs. DCR for obesity treatment. METHODS: The Daily Caloric Restriction vs. Intermittent Fasting Trial (DRIFT) is a two-arm, 52-week block randomized (1:1) clinical weight loss trial. The two intervention arms (DCR and IMF) are designed to prescribe an equivalent average weekly energy deficit from baseline weight maintenance energy requirements. Both DCR and IMF will be provided guideline-based behavioral support and a PA prescription. The primary outcome is change in body weight at 52 weeks. Secondary outcomes include changes in body composition (dual-energy x-ray absorptiometry (DXA)), metabolic parameters, total daily energy expenditure (TDEE, doubly labeled water (DLW)), EI (DLW intake-balance method, 7-day diet diaries), and patterns of physical activity (PA, activPAL device). DISCUSSION: Although DCR leads to modest weight loss success in the short-term, there is wide inter-individual variability in weight loss and poor long-term weight loss maintenance. Evidence-based dietary approaches to energy restriction that are effective long-term are needed to provide a range of evidence-based options to individuals seeking weight loss. The DRIFT study will evaluate the long-term effectiveness of IMF vs. DCR on changes in objectively measured weight, EI, and PA, when these approaches are delivered using guideline-based behavioral support and PA prescriptions.

Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease.

Progression of autosomal dominant polycystic kidney disease (ADPKD) is modified by metabolic defects and obesity. Indeed, reduced food intake slows cyst growth in preclinical rodent studies. Here, we demonstrate the feasibility of daily caloric restriction (DCR) and intermittent fasting (IMF) in a cohort of overweight or obese patients with ADPKD. Clinically significant weight loss occurred with both DCR and IMF; however, weight loss was greater and adherence and tolerability were better with DCR. Further, slowed kidney growth correlated with body weight and visceral adiposity loss independent of dietary regimen. Similarly, we compared the therapeutic efficacy of DCR, IMF, and time restricted feeding (TRF) using an orthologous ADPKD mouse model. Only ADPKD animals on DCR lost significant weight and showed slowed cyst growth compared to ad libitum, IMF, or TRF feeding. Collectively, this supports therapeutic feasibility of caloric restriction in ADPKD, with potential efficacy benefits driven by weight loss.

The Gut Microbiota during a Behavioral Weight Loss Intervention.

Altered gut microbiota has been linked to obesity and may influence weight loss. We are conducting an ongoing weight loss trial, comparing daily caloric restriction (DCR) to intermittent fasting (IMF) in adults who are overweight or obese. We report here an ancillary study of the gut microbiota and selected obesity-related parameters at the baseline and after the first three months of interventions. During this time, participants experienced significant improvements in clinical health measures, along with altered composition and diversity of fecal microbiota. We observed significant associations between the gut microbiota features and clinical measures, including weight and waist circumference, as well as changes in these clinical measures over time. Analysis by intervention group found between-group differences in the relative abundance of Akkermansia in response to the interventions. Our results provide insight into the impact of baseline gut microbiota on weight loss responsiveness as well as the early effects of DCR and IMF on gut microbiota.

Multiomic Predictors of Short-Term Weight Loss and Clinical Outcomes During a Behavioral-Based Weight Loss Intervention.

OBJECTIVE: Identifying predictors of weight loss and clinical outcomes may increase understanding of individual variability in weight loss response. We hypothesized that baseline multiomic features, including DNA methylation (DNAme), metabolomics, and gut microbiome, would be predictive of short-term changes in body weight and other clinical outcomes within a comprehensive weight loss intervention. METHODS: Healthy adults with overweight or obesity (n = 62, age 18-55 years, BMI 27-45 kg/m2 , 75.8% female) participated in a 1-year behavioral weight loss intervention. To identify baseline omic predictors of changes in clinical outcomes at 3 and 6 months, whole-blood DNAme, plasma metabolites, and gut microbial genera were analyzed. RESULTS: A network of multiomic relationships informed predictive models for 10 clinical outcomes (body weight, waist circumference, fat mass, hemoglobin A1c , homeostatic model assessment of insulin resistance, total cholesterol, triglycerides, C-reactive protein, leptin, and ghrelin) that changed significantly (P < 0.05). For eight of these, adjusted R2 ranged from 0.34 to 0.78. Our models identified specific DNAme sites, gut microbes, and metabolites that were predictive of variability in weight loss, waist circumference, and circulating triglycerides and that are biologically relevant to obesity and metabolic pathways. CONCLUSIONS: These data support the feasibility of using baseline multiomic features to provide insight for precision nutrition-based weight loss interventions.

The Impact of Timing of Exercise Initiation on Weight Loss: An 18-Month Randomized Clinical Trial.

OBJECTIVE: This study aimed to evaluate the impact of timing of exercise initiation on weight loss within a behavioral weight loss program. METHODS: Adults with overweight or obesity (N = 170; age 18-55 years; BMI 25-42 kg/m2 ; 83.5% women) were enrolled in an 18-month behavioral weight loss program consisting of a reduced-calorie diet, exercise, and group-based support. The standard group (STD) received a supervised exercise program (progressing to 300 min/wk of moderate-intensity aerobic exercise) during months 0 to 6. The sequential group (SEQ) was asked to refrain from changing exercise during months 0 to 6 and received the supervised exercise program during months 7 to 12. On completion of supervised exercise, both groups were instructed to continue 300 min/wk of moderate-intensity exercise for the study duration. RESULTS: At 6 months, the STD group exhibited greater reductions in body weight (-8.7 ± 0.7 kg) compared with the SEQ group (-6.9 ± 0.6 kg; P = 0.047). Between 6 and 18 months, the STD group regained more weight (2.5 ± 0.8 kg vs. 0.0 ± 0.8 kg; P = 0.02). At 18 months, there were no between-group differences in changes in weight (STD: -6.9 ± 1.2 kg; SEQ: -7.9 ± 1.2 kg), fat mass, lean mass, physical activity, or attrition. CONCLUSIONS: Both immediate and delayed exercise initiation within a behavioral weight loss program resulted in clinically meaningful weight loss at 18 months. Thus, timing of exercise initiation can be personalized based on patient preference.

Randomized controlled trial of Micro-Mobile Compression® on lactate clearance and subsequent exercise performance in elite male cyclists.

BACKGROUND: The purpose of this paper was to assess the feasibility of Micro-Mobile Compression® (MMC) on lactate clearance following exhaustive exercise and on subsequent exercise performance. METHODS: Elite male cyclists were randomized to MMC (n = 8) or passive recovery (control, n = 8). MMC is incorporated into a sandal that intermittently compresses the venous plexus during non-weight bearing to augment venous return. On day 1, subjects performed a graded exercise test on a cycle ergometer followed by 60 minutes of seated recovery, with or without MMC. Blood lactate concentration ([La(-)]) was measured during exercise and recovery. Subjects returned home for 3 more hours of seated recovery, with or without MMC. On days 2 and 3, subjects exercised to exhaustion in a fixed-load cycle ergometer test at 85% peak power and then repeated the day 1 post-exercise recovery procedures. Lactate clearance data after the time to exhaustion tests on days 2 and 3 were averaged to adjust for interday variation. RESULTS: On the day after MMC or control recovery, mean time to exhaustion was 15% longer (mean difference, 2.1 minutes) in the MMC group (P = 0.30). The standardized mean difference of MMC for time to exhaustion was 0.55, defined as a moderate treatment effect. Following the graded exercise test, area under the 60-minute lactate curve was nonsignificantly lower with MMC (3.2 ± 0.4 millimolar [mM]) versus control (3.5 ± 0.4 mM, P = 0.10) and times from end of exercise to 4mM and 2mM were 2.1 minutes (P = 0.58) and 7.2 minutes (P = 0.12) shorter, although neither achieved statistical significance. Following time to exhaustion testing, the area under the 60-minute lactate curve was lower with MMC (3.2 ± 0.2 mM) versus control (3.5 ± 0.2 mM, P = 0.02) and times from end of exercise to 4mM and 2mM were 4.4 minutes (P = 0.02) and 7.6 minutes (P < 0.01) faster. The standardized mean difference of MMC on most lactate clearance parameters was >0.8, defined as a large treatment effect. CONCLUSION: MMC yields large treatment effects on lactate clearance following high-intensity exercise and moderate treatment effects on subsequent exercise performance in elite male cyclists.