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Dietary carbohydrate and the risk of type 2 diabetes: an updated systematic review and dose-response meta-analysis of prospective cohort studies.
Hosseini, F, Jayedi, A, Khan, TA, Shab-Bidar, S
Scientific reports. 2022;(1):2491
Abstract
We did this study to clarify the association between carbohydrate intake and the risk of type 2 diabetes (T2D) and potential effect modification by geographical location. PubMed, Scopus and Web of Science were searched to find prospective cohort studies of dietary carbohydrate intake and T2D risk. A random-effects dose-response meta-analysis was performed to calculate the summary hazard ratios (HRs) and 95%CIs. The quality of cohort studies and the certainty of evidence was rated using the Newcastle-Ottawa Scale and GRADE tool, respectively. Eighteen prospective cohort studies with 29,229 cases among 607,882 participants were included. Thirteen studies were rated to have high quality, and five as moderate quality. The HR for the highest compared with the lowest category of carbohydrate intake was 1.02 (95%CI: 0.91, 1.15; I2 = 67%, GRADE = low certainty). The HRs were 0.93 (95%CI: 0.82, 1.05; I2 = 58%, n = 7) and 1.26 (95%CI: 1.11, 1.44; I2 = 6%, n = 6) in Western and Asian countries, respectively. Dose-response analysis indicated a J shaped association, with the lowest risk at 50% carbohydrate intake (HR50%: 0.95, 95%CI: 0.90, 0.99) and with risk increasing significantly at 70% carbohydrate intake (HR70%: 1.18, 95%CI: 1.03, 1.35). There was no association between low carbohydrate diet score and the risk of T2D (HR: 1.14, 95%CI: 0.89, 1.47; I2 = 90%, n = 5). Carbohydrate intake within the recommended 45-65% of calorie intake was not associated with an increased risk of T2D. Carbohydrate intake more than 70% calorie intake might be associated with a higher risk.
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Coingestion of Carbohydrate and Protein on Muscle Glycogen Synthesis after Exercise: A Meta-analysis.
Margolis, LM, Allen, JT, Hatch-McChesney, A, Pasiakos, SM
Medicine and science in sports and exercise. 2021;(2):384-393
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INTRODUCTION/PURPOSE Evidence suggests that carbohydrate and protein (CHO-PRO) ingestion after exercise enhances muscle glycogen repletion to a greater extent than carbohydrate (CHO) alone. However, there is no consensus at this point, and results across studies are mixed, which may be attributable to differences in energy content and carbohydrate intake relative to body mass consumed after exercise. The purpose of this study was determine the overall effects of CHO-PRO and the independent effects of energy and relative carbohydrate content of CHO-PRO supplementation on postexercise muscle glycogen synthesis compared with CHO alone. METHODS Meta-analysis was conducted on crossover studies assessing the influence of CHO-PRO compared with CHO alone on postexercise muscle glycogen synthesis. Studies were identified in a systematic review from PubMed and Cochrane Library databases. Data are presented as effect size (95% confidence interval [CI]) using Hedges' g. Subgroup analyses were conducted to evaluate effects of isocaloric and nonisocaloric energy content and dichotomized by median relative carbohydrate (high, ≥0.8 g·kg-1⋅h-1; low, <0.8 g·kg-1⋅h-1) content on glycogen synthesis. RESULTS Twenty studies were included in the analysis. CHO-PRO had no overall effect on glycogen synthesis (0.13, 95% CI = -0.04 to 0.29) compared with CHO. Subgroup analysis found that CHO-PRO had a positive effect (0.26, 95% CI = 0.04-0.49) on glycogen synthesis when the combined intervention provided more energy than CHO. Glycogen synthesis was not significant (-0.05, 95% CI = -0.23 to 0.13) in CHO-PRO compared with CON when matched for energy content. There was no statistical difference of CHO-PRO on glycogen synthesis in high (0.07, 95% CI = -0.11 to 0.22) or low (0.21, 95% CI = -0.08 to 0.50) carbohydrate content compared with CHO. CONCLUSION Glycogen synthesis rates are enhanced when CHO-PRO are coingested after exercise compared with CHO only when the added energy of protein is consumed in addition to, not in place of, carbohydrate.
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Meta-Analysis of Carbohydrate Solution Intake during Prolonged Exercise in Adults: From the Last 45+ Years' Perspective.
Bourdas, DI, Souglis, A, Zacharakis, ED, Geladas, ND, Travlos, AK
Nutrients. 2021;(12)
Abstract
Carbohydrate (CHO) supplementation during prolonged exercise postpones fatigue. However, the optimum administration timing, dosage, type of CHO intake, and possible interaction of the ergogenic effect with athletes' cardiorespiratory fitness (CRF) are not clear. Ninety-six studies (from relevant databases based on predefined eligibility criteria) were selected for meta-analysis to investigate the acute effect of ≤20% CHO solutions on prolonged exercise performance. The between-subject standardized mean difference [SMD = ([mean post-value treatment group-mean post-value control group]/pooled variance)] was assessed. Overall, SMD [95% CI] of 0.43 [0.35, 0.51] was significant (p < 0.001). Subgroup analysis showed that SMD was reduced as the subjects' CRF level increased, with a 6-8% CHO solution composed of GL:FRU improving performance (exercise: 1-4 h); administration during the event led to a superior performance compared to administration before the exercise, with a 6-8% single-source CHO solution increasing performance in intermittent and 'stop and start' sports and an ~6% CHO solution appearing beneficial for 45-60 min exercises, but there were no significant differences between subjects' gender and age groups, varied CHO concentrations, doses, or types in the effect measurement. The evidence found was sound enough to support the hypothesis that CHO solutions, when ingested during endurance exercise, have ergogenic action and a possible crossover interaction with the subject's CRF.
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Do Lower-Carbohydrate Diets Increase Total Energy Expenditure? An Updated and Reanalyzed Meta-Analysis of 29 Controlled-Feeding Studies.
Ludwig, DS, Dickinson, SL, Henschel, B, Ebbeling, CB, Allison, DB
The Journal of nutrition. 2021;(3):482-490
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BACKGROUND The effect of macronutrient composition on total energy expenditure (TEE) remains controversial, with divergent findings among studies. One source of heterogeneity may be study duration, as physiological adaptation to lower carbohydrate intake may require 2 to 3 wk. OBJECTIVE We tested the hypothesis that the effects of carbohydrate [expressed as % of energy intake (EI)] on TEE vary with time. METHODS The sample included trials from a previous meta-analysis and new trials identified in a PubMed search through 9 March 2020 comparing lower- and higher-carbohydrate diets, controlled for EI or body weight. Three reviewers independently extracted data and reconciled discrepancies. Effects on TEE were pooled using inverse-variance-weighted meta-analysis, with between-study heterogeneity assessed using the I2 statistic. Meta-regression was used to quantify the influence of study duration, dichotomized at 2.5 wk. RESULTS The 29 trials ranged in duration from 1 to 140 d (median: 4 d) and included 617 participants. Difference in carbohydrate between intervention arms ranged from 8% to 77% EI (median: 30%). Compared with reported findings in the prior analysis (I2 = 32.2%), we found greater heterogeneity (I2 = 90.9% in the reanalysis, 81.6% in the updated analysis). Study duration modified the diet effect on TEE (P < 0.001). Among 23 shorter trials, TEE was reduced on lower-carbohydrate diets (-50.0 kcal/d; 95% CI: -77.4, -22.6 kcal/d) with substantial heterogeneity (I2 = 69.8). Among 6 longer trials, TEE was increased on low-carbohydrate diets (135.4 kcal/d; 95% CI: 72.0, 198.7 kcal/d) with low heterogeneity (I2 = 26.4). Expressed per 10% decrease in carbohydrate as %EI, the TEE effects in shorter and longer trials were -14.5 kcal/d and 50.4 kcal/d, respectively. Findings were materially unchanged in sensitivity analyses. CONCLUSIONS Lower-carbohydrate diets transiently reduce TEE, with a larger increase after ∼2.5 wk. These findings highlight the importance of longer trials to understand chronic macronutrient effects and suggest a mechanism whereby lower-carbohydrate diets may facilitate weight loss.
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Effect of dietary carbohydrate and lipid modification on clinical and anthropometric parameters in nonalcoholic fatty liver disease: a systematic review and meta-analysis.
Garcêz, LS, Avelar, CR, Fonseca, NSS, Costa, PRF, Lyra, AC, Cunha, CM, Jesus, RP, Oliveira, LPM
Nutrition reviews. 2021;(12):1321-1337
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the adult population, making it one of the most common chronic liver diseases worldwide and a major public health problem. Still, there is no consensus on the most appropriate nutritional intervention for disease treatment. OBJECTIVE To systematize and synthesize the results of randomized controlled trials that have evaluated the effect of dietary interventions with different, quantitative, macronutrient compositions on hepatic steatosis attenuation, serum levels of alanine aminotransferase, aspartate aminotransferase, lipid profile, glucose metabolism markers, and anthropometric parameters of adults and the elderly (age ≥ 60 years) with NAFLD. DATA SOURCES MEDLINE databases via PubMed, Embase, Science Direct, LILACS, Web of Science, ClinicalTrials.gov, and Cochrane Library were searched. Randomized controlled trials that compared interventions as diets with values ≤ 45% or 20% of the total daily energy intake from carbohydrates or lipids, respectively, compared with dietary reference intakes, were included. DATA EXTRACTION Risk of bias was assessed through the Cochrane Collaboration tool. The meta-analysis was only performed to evaluate the effect of carbohydrate-modified diets on the outcome variables. The number of participants and mean values and respective standard deviations of the outcome variables were extracted and used to calculate weighted mean differences and their respective 95%CIs. RESULTS The search strategy resulted in 21 146 studies, of which 10 were retained for qualitative analysis and 6 were included in the meta-analysis. From the analysis of 10 studies were identified 8 articles in which low-calorie diets were evaluated and 3 interventions that used an isocaloric diet. Only 3 studies were classified as having low risk of bias. CONCLUSION The observed effects on hepatic steatosis, serum alanine aminotransferase and aspartate aminotransferase levels, parameters of lipid and glucose metabolism, and anthropometric variables were mostly related to a hypocaloric diet. The use of reduced macronutrient interventions had no efficacy. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42018088824.
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Insulin strategies for dietary fat and protein in type 1 diabetes: A systematic review.
Smith, TA, Marlow, AA, King, BR, Smart, CE
Diabetic medicine : a journal of the British Diabetic Association. 2021;(11):e14641
Abstract
AIM: To identify and report the efficacy of insulin strategies used to manage glycaemia following fat and/or fat and protein meals in type 1 diabetes. METHODS A systematic literature search of medical databases from 1995 to 2021 was undertaken. Inclusion criteria were randomised controlled trials that reported at least one of the following glycaemic outcomes: mean glucose, area under the curve, time in range or hypoglycaemic episodes. RESULTS Eighteen studies were included. Thirteen studies gave additional insulin. Five studies gave an additional 30%-43% of the insulin-to-carbohydrate ratio (ICR) for 32-50 g of fat and 31%-51% ICR for 7-35 g of fat with 12-27 g of protein added to control meals. A further eight studies gave -28% to +75% ICR using algorithms based on fat and protein for meals with 19-50 g of carbohydrate, 2-79 g of fat and 10-60 g of protein, only one study reported a glycaemic benefit of giving less than an additional 24% ICR. Eight studies evaluated insulin delivery patterns. Four of six studies in pump therapy, and one of two studies in multiple daily injections showed the combination of bolus and split dose, respectively, were superior. Five studies examined the insulin dose split, four demonstrated 60%-125% ICR upfront was necessary. Two studies investigated the timing of insulin delivery, both reported administration 15 min before the meal lowered postprandial glycaemia. CONCLUSIONS Findings highlight the glycaemic benefit of an additional 24%-75% ICR for fat and fat and protein meals. For these meals, there is supportive evidence for insulin delivery in a combination bolus with a minimum upfront dose of 60% ICR, 15 min before the meal.
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The Effect of Preoperative Carbohydrate Loading on Clinical and Biochemical Outcomes after Cardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Trials.
Kotfis, K, Jamioł-Milc, D, Skonieczna-Żydecka, K, Folwarski, M, Stachowska, E
Nutrients. 2020;(10)
Abstract
BACKGROUND AND AIM Preoperative fasting leads to metabolic stress and causes insulin resistance in patients undergoing cardiac surgery. The aim of this study was to assess the effect of preoperative oral carbohydrate loading (OCH) on outcome in patients undergoing planned cardiac surgery by systematically reviewing the literature and synthesizing evidence from randomized controlled trials (RCTs). METHODS Systematic search of PubMed/MEDLINE/Embase/Cinahl/Web of Science/ClinicalTrials databases was performed to identify relevant RCTs from databased inception until 05/03/2020. We included studies that compared outcome measures between OCH with control (placebo or standard starvation). We conducted a random-effect meta-analysis of clinical and biochemical parameters. RESULTS Nine studies (N = 9) were included with a total of 507 patients. OCH significantly decreased aortic clamping duration (n = 151, standardized mean difference (SMD) = -0.28, 95% confidence interval (CI) = -0.521 to -0.038, p = 0.023 and differences in means (DM) = -6.388, 95%CI = -11.246 to -1.529, p = 0.010). Patients from treatment groups had shorter intensive care unit (ICU) stay (n = 202, SMD = -0.542, 95%CI = -0.789 to -0.295, p < 0.001 and DM = -25.925, 95%CI = -44.568 to -7.283, p = 0.006) and required fewer units of insulin postoperatively (n = 85, SMD = -0.349, 95%CI = -0.653 to -0.044, p = 0.025 and DM = -4.523, 95%CI = -8.417 to -0.630, p = 0.023). The necessity to use inotropic drugs was significantly lower in the OCH group (risk ratio (RR) = 0.795, 95%CI = 0.689 to 0.919, p = 0.002). All other primary outcomes did not reveal a significant effect. CONCLUSIONS Preoperative OCH in patients undergoing cardiac surgery demonstrated a 20% reduction in the use of inotropic drugs, a 50% reduction of the length of ICU stay, a 28% decrease in aortic clamping duration and a 35% decrease of postoperative insulin requirement.
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Carbohydrate and fat intake associated with risk of metabolic diseases through epigenetics of CPT1A.
Lai, CQ, Parnell, LD, Smith, CE, Guo, T, Sayols-Baixeras, S, Aslibekyan, S, Tiwari, HK, Irvin, MR, Bender, C, Fei, D, et al
The American journal of clinical nutrition. 2020;(5):1200-1211
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BACKGROUND Epigenome-wide association studies identified the cg00574958 DNA methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with reduced risk of metabolic diseases (hypertriglyceridemia, obesity, type 2 diabetes, hypertension, metabolic syndrome), but the mechanism underlying these associations is unknown. OBJECTIVES We aimed to elucidate whether carbohydrate and fat intakes modulate cg00574958 methylation and the risk of metabolic diseases. METHODS We examined associations between carbohydrate (CHO) and fat (FAT) intake, as percentages of total diet energy, and the CHO/FAT ratio with CPT1A-cg00574958, and the risk of metabolic diseases in 3 populations (Genetics of Lipid Lowering Drugs and Diet Network, n = 978; Framingham Heart Study, n = 2331; and REgistre GIroní del COR study, n = 645) while adjusting for confounding factors. To understand possible causal effects of dietary intake on the risk of metabolic diseases, we performed meta-analysis, CPT1A transcription analysis, and mediation analysis with CHO and FAT intakes as exposures and cg00574958 methylation as the mediator. RESULTS We confirmed strong associations of cg00574958 methylation with metabolic phenotypes (BMI, triglyceride, glucose) and diseases in all 3 populations. Our results showed that CHO intake and CHO/FAT ratio were positively associated with cg00574958 methylation, whereas FAT intake was negatively correlated with cg00574958 methylation. Meta-analysis further confirmed this strong correlation, with β = 58.4 ± 7.27, P = 8.98 x 10-16 for CHO intake; β = -36.4 ± 5.95, P = 9.96 x 10-10 for FAT intake; and β = 3.30 ± 0.49, P = 1.48 x 10-11 for the CHO/FAT ratio. Furthermore, CPT1A mRNA expression was negatively associated with CHO intake, and positively associated with FAT intake, and metabolic phenotypes. Mediation analysis supports the hypothesis that CHO intake induces CPT1A methylation, hence reducing the risk of metabolic diseases, whereas FAT intake inhibits CPT1A methylation, thereby increasing the risk of metabolic diseases. CONCLUSIONS Our results suggest that the proportion of total energy supplied by CHO and FAT can have a causal effect on the risk of metabolic diseases via the epigenetic status of CPT1A.Study registration at https://www.clinicaltrials.gov/: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)-NCT01023750; and the Framingham Heart Study (FHS)-NCT00005121.
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Ketogenic diets for drug-resistant epilepsy.
Martin-McGill, KJ, Bresnahan, R, Levy, RG, Cooper, PN
The Cochrane database of systematic reviews. 2020;(6):CD001903
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BACKGROUND Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial for children with drug-resistant epilepsy. This is an update of a review first published in 2003, and last updated in 2018. OBJECTIVES To assess the effects of ketogenic diets for people with drug-resistant epilepsy. SEARCH METHODS For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 26 April 2019) on 29 April 2019. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised controlled trials (RCTs) from Embase, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional relevant studies. SELECTION CRITERIA RCTs or quasi-RCTs of KDs for people of any age with drug-resistant epilepsy. DATA COLLECTION AND ANALYSIS Two review authors independently applied predefined criteria to extract data and evaluated study quality. We assessed the outcomes: seizure freedom, seizure reduction (50% or greater reduction in seizure frequency), adverse effects, cognition and behaviour, quality of life, and attrition rate. We incorporated a meta-analysis. We utilised an intention-to-treat (ITT) population for all primary analyses. We presented the results as risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS We identified 13 studies with 932 participants; 711 children (4 months to 18 years) and 221 adults (16 years and over). We assessed all 13 studies to be at high risk of performance and detection bias, due to lack of blinding. Assessments varied from low to high risk of bias for all other domains. We rated the evidence for all outcomes as low to very low certainty. Ketogenic diets versus usual care for children Seizure freedom (RR 3.16, 95% CI 1.20 to 8.35; P = 0.02; 4 studies, 385 participants; very low-certainty evidence) and seizure reduction (RR 5.80, 95% CI 3.48 to 9.65; P < 0.001; 4 studies, 385 participants; low-certainty evidence) favoured KDs (including: classic KD, medium-chain triglyceride (MCT) KD combined, MCT KD only, simplified modified Atkins diet (MAD) compared to usual care for children. We are not confident that these estimated effects are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea for both the intervention and usual care group, but the true effect could be substantially different (low-certainty evidence). Ketogenic diet versus usual care for adults In adults, no participants experienced seizure freedom. Seizure reduction favoured KDs (MAD only) over usual care but, again, we are not confident that the effect estimated is accurate (RR 5.03, 95% CI 0.26 to 97.68; P = 0.29; 2 studies, 141 participants; very low-certainty evidence). Adults receiving MAD most commonly reported vomiting, constipation and diarrhoea (very low-certainty evidence). One study reported a reduction in body mass index (BMI) plus increased cholesterol in the MAD group. The other reported weight loss. The true effect could be substantially different to that reported. Ketogenic diet versus ketogenic diet for children Up to 55% of children achieved seizure freedom with a classical 4:1 KD after three months whilst up to 85% of children achieved seizure reduction (very low-certainty evidence). One trial reported a greater incidence of seizure reduction with gradual-onset KD, as opposed to fasting-onset KD. Up to 25% of children were seizure free with MAD and up to 60% achieved seizure reduction. Up to 25% of children became seizure free with MAD and up to 60% experienced seizure reduction. One study used a simplified MAD (sMAD) and reported that 15% of children gained seizure freedom rates and 56% achieved seizure reduction. We judged all the evidence described as very low certainty, thus we are very unsure whether the results are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea (5 studies, very low-certainty evidence). Two studies reported weight loss. One stated that weight loss and gastrointestinal disturbances were more frequent, with 4:1 versus 3:1 KD, whilst one reported no difference in weight loss with 20 mg/d versus 10 mg/d carbohydrates. In one study, there was a higher incidence of hypercalcuria amongst children receiving classic KD compared to MAD. All effects described are unlikely to be accurate. Ketogenic diet versus ketogenic diet for adults One study randomised 80 adults (aged 18 years and over) to either MAD plus KetoCal during the first month with MAD alone for the second month, or MAD alone for the first month followed by MAD plus KetoCal for the second month. No adults achieved seizure freedom. More adults achieved seizure reduction at one month with MAD alone (42.5%) compared to MAD plus KetoCal (32.5%), however, by three months only 10% of adults in both groups maintained seizure reduction. The evidence for both outcomes was of very low certainty; we are very uncertain whether the effects are accurate. Constipation was more frequently reported in the MAD plus KetoCal group (17.5%) compared to the MAD only group (5%) (1 study, very low-certainty evidence). Diarrhoea and increase/change in seizure pattern/semiology were also commonly reported (17.5% to 20% of participants). The true effects of the diets could be substantially different to that reported. AUTHORS' CONCLUSIONS The evidence suggests that KDs could demonstrate effectiveness in children with drug-resistant epilepsy, however, the evidence for the use of KDs in adults remains uncertain. We identified a limited number of studies which all had small sample sizes. Due to the associated risk of bias and imprecision caused by small study populations, the evidence for the use of KDs was of low to very low certainty. More palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but could be associated with fewer adverse effects. This assumption requires more investigation. For people who have drug-resistant epilepsy or who are unsuitable for surgical intervention, KDs remain a valid option. Further research is required, particularly for adults with drug-resistant epilepsy.
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The Effect of Ingesting Carbohydrate and Proteins on Athletic Performance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Kloby Nielsen, LL, Tandrup Lambert, MN, Jeppesen, PB
Nutrients. 2020;(5)
Abstract
Endurance athletes participating in sporting events may be required to complete multiple training sessions a day or on successive days with a limited recovery time. Nutritional interventions that enhance the restoration of endogenous fuel stores (e.g., liver and muscle glycogen) and improve muscle damage repair have received a lot of attention. The purpose of this review is to investigate the effect of ingesting carbohydrate (CHO) and protein (PRO) on athletic performance. Studies were identified by searching the electronic databases PubMed and EMBASE. Random-effects meta-analyses were conducted to examine the intervention efficacy. A total of 30 randomized controlled trials (RCT), comprising 43 trials and 326 participants in total, were included in this review. The meta-analysis showed an overall significant effect in Time-To-Exhaustion (TTE) and Time-Trial (TT) performance, when ingesting carbohydrates and proteins (CHO-PRO) compared to CHO-only (p = 0.03 and p = 0.0007, respectively). A subgroup analysis demonstrated a significant effect in TTE by ingesting CHO-PRO compared to CHO, when supplements were provided during and/or following an exercise bout. CHO-PRO significantly improved TTE compared to CHO-only, when a long-term recovery (i.e., ≥8 h) was implemented (p = 0.001). However, no effect was found when the recovery time was short-term (i.e., ≤8 h). No significant effect was observed when CHO-PRO and CHO-only supplements were isocaloric. However, a significant improved TTE was evident with CHO-PRO compared to CHO-only, when the supplements were matched for carbohydrate content (p < 0.00001). In conclusion, co-ingesting carbohydrates and proteins appears to enhance TTE and TT performance compared to CHO-only and presents a compelling alternate feeding strategy for athletes.