Whole-Grain Intake in the Mediterranean Diet and a Low Protein to Carbohydrates Ratio Can Help to Reduce Mortality from Cardiovascular Disease, Slow Down the Progression of Aging, and to Improve Lifespan: A Review.

Increase in the aging population is a phenomenon all over the world. Maintaining good functional ability, good mental health, and cognitive function in the absence of severe disease and physical disability define successful aging. A healthy lifestyle in middle age predisposes successful aging. Longevity is the result of a multifactorial phenomenon, which involves feeding. Diets that emphasize fruit and vegetables, whole grains rather than refined grains, low-fat dairy, lean meats, fish, legumes, and nuts are inversely associated with mortality or to a lower risk of becoming frail among elderly subjects. A regular physical activity and a regular intake of whole grain derivatives together with the optimization of the protein/carbohydrate ratio in the diet, where the ratio is significantly less than 1 such as in the Mediterranean diet and the Okinawan diet, reduces the risk of developing aging-related diseases and increases healthy life expectancy. The purpose of our review was to analyze cohort and case-control studies that investigated the effects of cereals in the diet, especially whole grains and derivatives as well as the effects of a diet with a low protein-carbohydrate ratio on the progression of aging, mortality, and lifespan.

Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet.

The effects of ketoanalogues (KA) supplementation on mortality and progression to dialysis in patients with pre-dialysis stage 5 chronic kidney disease (CKD) receiving a low-protein diet (LPD) remain ambiguous. From Taiwan's National Health Insurance Research Database during 1996-2011, 165 patients with pre-dialysis CKD on an LPD (0.6 g/kg/day) with KA supplementation were matched with 165 patients with pre-dialysis CKD on an LPD without KA supplementation. Of the 165 patients with advanced CKD receiving KA supplementation, 34 (20.6%) died, and 124 (75.2%) underwent long-term dialysis during the study period. There was no significant difference in mortality between the KA-user group and the KA-nonuser group (adjusted hazard ratio [HR], 1.41; 95% confidence interval [CI], 0.68-2.93; p = 0.355). KA supplementation significantly increased long-term dialysis risk (adjusted HR, 1.41; 95% CI, 1.04-1.90; p = 0.025) and combined outcome risk (defined as long-term dialysis and death; adjusted HR, 1.37; 95% CI, 1.02-1.83; p = 0.034). KA supplementation also increased long-term dialysis risk (adjusted HR, 1.49; 95% CI, 1.00-2.20; p = 0.048) in the subgroup of pre-dialysis patients with diabetes mellitus (DM), but not in those patients without DM. In conclusion, KA supplementation might increase long-term dialysis risk in patients with advanced CKD receiving an LPD, but it did not increase mortality.

Veganism, aging and longevity: new insight into old concepts.

PURPOSE OF REVIEW: Plant-based diets are associated with better health and longevity. Veganism is a strict form of vegetarianism, which has gained increasing attention in recent years. This review will focus on studies addressing mortality and health-span in vegans and vegetarians and discuss possible longevity-enhancing mechanisms. RECENT FINDINGS: Studies in vegans are still limited. Epidemiologic studies consistently show lower disease rates, such as lower incidence of cancer and cardiovascular disease, but mortality rates are comparable with rates in vegetarians and occasional meat eaters. Reasons for following strict vegan diets differ, which may affect diet quality, and thus health and life-span. New insights into some characteristics of veganism, such as protein restriction or restriction in certain amino acids (leucine or methionine) show potentially life-span-enhancing potential. Veganism improves insulin resistance and dyslipidemia and associated abnormalities. Gut microbiota as mediator of dietary impact on host metabolism is more diverse in vegans and has been suggested to be a health-promoting factor. Vegan diets do not fulfill the requirements of children, pregnant women or old individuals who should receive adequate supplements. SUMMARY: There is substantial evidence that plant-based diets are associated with better health but not necessarily lower mortality rates. The exact mechanisms of health promotion by vegan diets are still not entirely clear but most likely multifactorial. Reasons for and quality of the vegan diet should be assessed in longevity studies.

Effects of dietary protein intake on renal outcome and mortality in patients with advanced diabetic nephropathy.

BACKGROUND: The difficulty of adhering to a low-protein diet is a serious limitation of randomized controlled trials aimed at validating the efficacy of this therapy. In this observational study of patients with diabetic nephropathy, we examined the association of dietary protein intake (DPI) with renal outcome and mortality, taking into account the nutritional status. METHODS: We conducted a single-center historical cohort study of 449 adult Japanese patients with type 2 diabetes and the urinary albumin-to-creatinine ratio of ≥ 300 mg/g or estimated glomerular filtration rate of < 30 mL/min/1.73 m2. DPI was estimated with a formula using nitrogen levels in spot urine and body mass index. Malnutrition was defined as the Geriatric Nutritional Risk Index of ≤ 98. The primary and secondary endpoints were renal replacement therapy (RRT) initiation and mortality before RRT initiation, respectively. The Fine and Gray subdistribution hazard model was used to determine the relative effects of DPI on the respective endpoint. RESULTS: Decreased DPI was associated with lower incidence of RRT with an adjusted hazard ratio of 0.81 (95% confidence interval: 0.72-0.92, p < 0.001). The interaction between DPI and nutritional status with respect to mortality was significant (p interaction = 0.047). Decreased DPI was a risk factor for mortality in patients with malnutrition (p = 0.009) but not in those without malnutrition (p = 0.559). CONCLUSIONS: In patients with type 2 diabetic nephropathy, lower DPI was associated with lower incidence of RRT initiation, suggesting beneficial effects of a low-protein diet on kidneys. Conversely, lower DPI might lead to increased mortality in patients with malnutrition.

Dietary satisfaction and quality of life in chronic kidney disease patients on low-protein diets: a multicentre study with long-term outcome data (TOrino-Pisa study).

BACKGROUND: Concerns about adherence and quality of life (QoL) limit the diffusion of low-protein diets (LPDs) as a way to slow chronic kidney disease (CKD) progression and postpone dialysis. The aim of this multicentre study is to assess dietary satisfaction in stable CKD patients. METHODS: This was a multicentre cross-sectional study with long-term follow-up data. Prevalent patients on LPD for at least 6 months were selected in four Italian centres. QoL was assessed using the World Health Organization Quality of Life questionnaire, and diet satisfaction with the Modification of Diet in Renal Disease satisfaction questionnaire. Comorbidity was assessed by Charlson Comorbidity Index, estimated glomerular filtration rate (eGFR) was calculated by the CKD Epidemiology Collaboration equation and protein intake by Maroni-Mitch formula. Survival was analysed with Kaplan-Meier curves and Cox Proportional Hazard Model. RESULTS: Four hundred and twenty-two CKD Stages 3-5 patients were enrolled. Over 95% were on moderately restricted diets (0.6 g/kg/day). Compliance was good (protein intake: 0.59 g/kg/day at baseline, 0.72 at the end of follow-up). Median dietary satisfaction was 4 on a 1-5 scale. QoL was not affected by the type of diet, but was influenced by age, comorbidity and setting of care. Two years later, at the end of follow-up, 66.6% of the patients were still on a diet; the main causes of discontinuation were dialysis and death. The dropout rate was low (5.5%); in Cox analysis, patient and renal survival were influenced by age and eGFR, but not by QoL, setting of care or type of diet. CONCLUSIONS: LPDs are compatible with high dietary satisfaction and minimal dropout, at least in patients who are able to follow such a diet for at least 6 months.

Circadian clock genes' overexpression in Drosophila alters diet impact on lifespan.

Diet restriction is one of the most accurately confirmed interventions which extend lifespan. Genes coding circadian core clock elements are known to be the key controllers of cell metabolism especially in aging aspect. The molecular mechanisms standing behind the phenomenon of diet-restriction-mediated life extension are connected to circadian clock either. Here we investigate the effects of protein-rich and low-protein diets on lifespan observed in fruit flies overexpressing core clock genes (cry, per, Clk, cyc and tim). The majority of core clock genes being upregulated in peripheral tissues (muscles and fat body) on protein-rich diet significantly decrease the lifespan of male fruit flies from 5 to 61%. Nevertheless, positive increments of median lifespan were observed in both sexes, males overexpressing cry in fat body lived 20% longer on poor diet. Overexpression of per also on poor medium resulted in life extension in female fruit flies. Diet restriction reduces mortality caused by overexpression of core clock genes. Cox-regression model revealed that diet restriction seriously decreases mortality risks of flies which overexpress core clock genes. The hazard ratios are lower for flies overexpressing clock genes in fat body relatively to muscle-specific overexpression. The present work suggests a phenomenological view of how two peripheral circadian oscillators modify effects of rich and poor diets on lifespan and hazard ratios.

Low protein diets for non-diabetic adults with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is defined as reduced function of the kidneys present for 3 months or longer with adverse implications for health and survival. For several decades low protein diets have been proposed for participants with CKD with the aim of slowing the progression to end-stage kidney disease (ESKD) and delaying the onset of renal replacement therapy. However the relative benefits and harms of dietary protein restriction for preventing progression of CKD have not been resolved. This is an update of a systematic review first published in 2000 and updated in 2006 and 2009. OBJECTIVES: To determine the efficacy of low protein diets in preventing the natural progression of CKD towards ESKD and in delaying the need for commencing dialysis treatment in non-diabetic adults. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 2 March 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi RCTs in which adults with non-diabetic chronic kidney disease (stages 3 to 5) not on dialysis were randomised to receive a very low protein intake (0.3 to 0.4 g/kg/d) compared with a low protein intake (0.5 to 0.6 g/kg/d) or a low protein intake compared with a normal protein intake (≥ 0.8 g/kg/d) for 12 months or more. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and extracted data. For dichotomous outcomes (death, all causes), requirement for dialysis, adverse effects) the risk ratios (RR) with 95% confidence intervals (CI) were calculated and summary statistics estimated using the random effects model. Where continuous scales of measurement were used (glomerular filtration rate (GFR), weight), these data were analysed as the mean difference (MD) or standardised mean difference (SMD) if different scales had been used. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: We identified an additional six studies to include 17 studies with 2996 analysed participants (range 19 to 840). Four larger multicentre studies were subdivided according to interventions so that the review included 21 separate data sets. Mean duration of participant follow-up ranged from 12 to 50 months.Random sequence generation and allocation concealment were considered at low risk of bias in eleven and nine studies respectively. All studies were considered at high risk for performance bias as they were open-label studies. We assessed detection bias for outcome assessment for GFR and ESKD separately. As GFR measurement was a laboratory outcome all studies were assessed at low risk of detection bias. For ESKD, nine studies were at low risk of detection bias as the need to commence dialysis was determined by personnel independent of the study investigators. Five studies were assessed at high risk of attrition bias with eleven studies at low risk. Ten studies were at high risk for reporting bias as they did not include data which could be included in a meta-analysis. Eight studies reported funding from government bodies while the remainder did not report on funding.Ten studies compared a low protein diet with a normal protein diet in participants with CKD categories 3a and b (9 studies) or 4 (one study). There was probably little or no difference in the numbers of participants who died (5 studies 1680 participants: RR 0.77, 95% CI 0.51 to 1.18; 13 fewer deaths per 1000; moderate certainty evidence). A low protein diet may make little or no difference in the number of participants who reached ESKD compared with a normal protein diet (6 studies, 1814 participants: RR 1.05, 95% CI 0.73 to 1.53; 7 more per 1000 reached ESKD; low certainty evidence). It remains uncertain whether a low protein diet compared with a normal protein intake impacts on the outcome of final or change in GFR (8 studies, 1680 participants: SMD -0.18, 95% CI -0.75 to 0.38; very low certainty evidence).Eight studies compared a very low protein diet with a low protein diet and two studies compared a very low protein diet with a normal protein diet. A very low protein intake compared with a low protein intake probably made little or no difference to death (6 studies, 681 participants: RR 1.26, 95% CI 0.62 to 2.54; 10 more deaths per 1000; moderate certainty evidence). However it probably reduces the number who reach ESKD (10 studies, 1010 participants: RR 0.65, 95% CI 0.49 to 0.85; 165 per 1000 fewer reached ESKD; moderate certainty evidence). It remains uncertain whether a very low protein diet compared with a low or normal protein intake influences the final or change in GFR (6 studies, 456 participants: SMD 0.12, 95% CI -0.27 to 0.52; very low certainty evidence).Final body weight was reported in only three studies. It is uncertain whether the intervention alters final body weight (3 studies, 89 participants: MD -0.40 kg, 95% CI -6.33 to 5.52; very low certainty evidence).Twelve studies reported no evidence of protein energy wasting (malnutrition) in their study participants while three studies reported small numbers of participants in each group with protein energy wasting. Most studies reported that adherence to diet was satisfactory. Quality of life was not formally assessed in any studies. AUTHORS' CONCLUSIONS: This review found that very low protein diets probably reduce the number of people with CKD 4 or 5, who progress to ESKD. In contrast low protein diets may make little difference to the number of people who progress to ESKD. Low or very low protein diets probably do not influence death. However there are limited data on adverse effects such as weight differences and protein energy wasting. There are no data on whether quality of life is impacted by difficulties in adhering to protein restriction. Studies evaluating the adverse effects and the impact on quality of life of dietary protein restriction are required before these dietary approaches can be recommended for widespread use.

Does a Supplemental Low-Protein Diet Decrease Mortality and Adverse Events After Commencing Dialysis? A Nationwide Cohort Study.

BACKGROUND: A beneficial effect of a ketoanalogue-supplemented low-protein diet (sLPD) in postponing dialysis has been demonstrated in numerous previous studies. However, evidence regarding its effect on long-term survival is limited. Our study assessed the long-term outcomes of patients on an sLPD after commencing dialysis. METHODS: This retrospective study examined patients with new-onset end-stage renal disease with permanent dialysis between 2001 and 2013, extracted from Taiwan's National Health Insurance Research Database. Patients who received more than 3 months of sLPD treatment in the year preceding the start of dialysis were extracted. The outcomes studied were all-cause mortality, infection rate, and major cardiac and cerebrovascular events (MACCEs). RESULTS: After propensity score matching, the sLPD group (n = 2607) showed a lower risk of all-cause mortality (23.1% vs. 27.6%, hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.70⁻0.84), MACCEs (19.2% vs. 21.5%, HR 0.86, 95% CI 0.78⁻0.94), and infection-related death (9.9% vs. 12.5%, HR 0.76, 95% CI 0.67⁻0.87) than the non-sLPD group did. CONCLUSION: We found that sLPD treatment might be safe without long-term negative consequences after dialysis treatment.

Low Protein Intake in the Population: Low Risk of Kidney Function Decline but High Risk of Mortality.

OBJECTIVE: This population-based study investigated low protein intake, mortality, and kidney function decline. DESIGN: Observational longitudinal cohort study. SUBJECTS: Target cohort consisted of 4,679 adults participating in 1988-1992 and 2001-2007 examinations of the Gubbio Study (baseline and follow-up). Data collection included overnight urine urea nitrogen (UUN) and other variables at baseline, serum creatinine at baseline and follow-up, and mortality from baseline to follow-up. Three hundred seventy-two persons were excluded for missing data. UUN in the lowest 20% of the distribution was defined as low and used as index of low protein intake. Estimated glomerular filtration rate (eGFR, mL/minute × 1.73 m2) was used as kidney function index. INTERVENTION: None (observational study). MAIN OUTCOME MEASURE: Mortality and eGFR decline are the main outcome measures, and eGFR decline was defined as eGFR change from baseline to follow-up ≤ mean-1 standard deviation (Z-score ≤ -1). RESULTS: Eight hundred seventy-one deaths occurred over 15.9 ± 4.0 years of observation (417 from cardiovascular disease and 276 from neoplastic disease). Low UUN associated with mortality (hazard ratio, HR = 1.31, 95% confidence interval, CI = 1.12/1.53) due to association with mortality from neoplastic disease (HR = 1.33, 95% CI = 1.02/1.76). Mortality-corrected follow-up response rate was 79.9% (n = 2845). Baseline to follow-up eGFR change was -9.9 ± 10.1, and eGFR decline was found in 454 examinees. Low UUN associated with eGFR decline only in subgroup with baseline eGFR <90 (n = 1441, odds ratio = 0.44, 95% CI = 0.22/0.85). Low baseline eGFR interacted with the association between low UUN and eGFR decline (P = .024). CONCLUSION: Low protein intake predicted higher mortality in the whole population and lower incidence of eGFR decline only in subgroup with reduced kidney function.