Background
The objective of this study was to evaluate the role of low‐carbohydrate diets after breast cancer diagnosis in relation to breast cancer–specific and all‐cause mortality.
Methods
For 9621 ...women with stage I–III breast cancer from two ongoing cohort studies, the Nurses’ Health Study and Nurses’ Health Study II, overall low‐carbohydrate, animal‐rich low‐carbohydrate, and plant‐rich low‐carbohydrate diet scores were calculated by using food frequency questionnaires collected after breast cancer diagnosis.
Results
Participants were followed up for a median 12.4 years after breast cancer diagnosis. We documented 1269 deaths due to breast cancer and 3850 all‐cause deaths. With the use of Cox proportional hazards regression and after controlling for potential confounding variables, we observed a significantly lower risk of overall mortality among women with breast cancer who had greater adherence to overall low‐carbohydrate diets (hazard ratio for quintile 5 vs. quintile 1 HRQ5vsQ1, 0.82; 95% CI, 0.74–0.91; ptrend = .0001) and plant‐rich low‐carbohydrate diets (HRQ5vsQ1, 0.73; 95% CI, 0.66–0.82; ptrend < .0001) after breast cancer diagnosis but not animal‐rich low‐carbohydrate diets (HRQ5vsQ1, 0.93; 95% CI, 0.84–1.04; ptrend = .23). However, greater adherence to overall, animal‐rich, or plant‐rich low‐carbohydrate diets was not significantly associated with a lower risk of breast cancer–specific mortality.
Conclusions
This study showed that greater adherence to low‐carbohydrate diets, especially plant‐rich low‐carbohydrate diets, was associated with better overall survival but not breast cancer–specific survival among women with stage I–III breast cancer.
Greater adherence to low‐carbohydrate diets, especially plant‐rich low‐carbohydrate diets, was associated with better overall survival but not breast cancer–specific survival among women with stage I–III breast cancer.
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.
We tested the hypothesis that the effects of carbohydrate expressed as % of energy intake (EI) on TEE vary with time.
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.
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.
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.
Carbohydrates, which are ubiquitously distributed throughout the three domains of life, play significant roles in a variety of vital biological processes. Access to unique and homogeneous ...carbohydrate materials is important to understand their physical properties, biological functions, and disease-related features. It is difficult to isolate carbohydrates in acceptable purity and amounts from natural sources. Therefore, complex saccharides with well-defined structures are often most conviently accessed through chemical syntheses. Two major hurdles, regioselective protection and stereoselective glycosylation, are faced by carbohydrate chemists in synthesizing these highly complicated molecules. Over the past few years, there has been a radical change in tackling these problems and speeding up the synthesis of oligosaccharides. This is largely due to the development of one–pot protection, one–pot glycosylation, and one–pot protection–glycosylation protocols and streamlined approaches to orthogonally protected building blocks, including those from rare sugars, that can be used in glycan coupling. In addition, new automated strategies for oligosaccharide syntheses have been reported not only for program-controlled assembly on solid support but also by the stepwise glycosylation in solution phase. As a result, various sugar molecules with highly complex, large structures could be successfully synthesized. To summarize these recent advances, this review describes the methodologies for one-pot protection and their one-pot glycosylation into the complex glycans and the chronological developments associated with automated syntheses of oligosaccharides.
In the past, different types of diet with a generally low-carbohydrate content (< 50–< 20 g/day) have been promoted, for weight loss and diabetes, and the effectiveness of a very low dietary ...carbohydrate content has always been a matter of debate. A significant reduction in the amount of carbohydrates in the diet is usually accompanied by an increase in the amount of fat and to a lesser extent, also protein. Accordingly, using the term “low carb–high fat” (LCHF) diet is most appropriate. Low/very low intakes of carbohydrate food sources may impact on overall diet quality and long-term effects of such drastic diet changes remain at present unknown. This narrative review highlights recent metabolic and clinical outcomes of studies as well as practical feasibility of low LCHF diets. A few relevant observations are as follows: (1) any diet type resulting in reduced energy intake will result in weight loss and related favorable metabolic and functional changes; (2) short-term LCHF studies show both favorable and less desirable effects; (3) sustained adherence to a ketogenic LCHF diet appears to be difficult. A non-ketogenic diet supplying 100–150 g carbohydrate/day, under good control, may be more practical. (4) There is lack of data supporting long-term efficacy, safety and health benefits of LCHF diets. Any recommendation should be judged in this light. (5) Lifestyle intervention in people at high risk of developing type 2 diabetes, while maintaining a relative carbohydrate-rich diet, results in long-term prevention of progression to type 2 diabetes and is generally seen as safe.
Abstract The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health ...and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.
To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.
Randomized trial.
Multicenter collaboration at US two sites, August 2014 to May 2017.
164 adults ...aged 18-65 years with a body mass index of 25 or more.
After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).
The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.
Total energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval -29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (-6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).
Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.
ClinicalTrials.gov NCT02068885.
High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel ...insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation.
Overall quality of dietary carbohydrate intake rather than total carbohydrate intake may determine the risk of cardiovascular disease (CVD).
We examined 6- and 12-mo changes in carbohydrate quality ...index (CQI) and concurrent changes in several CVD risk factors in a multicenter, randomized, primary-prevention trial (PREDIMED-Plus) based on an intensive weight-loss lifestyle intervention program.
Prospective analysis of 5373 overweight/obese Spanish adults (aged 55–75 y) with metabolic syndrome (MetS). Dietary intake information obtained from a validated 143-item semiquantitative food-frequency questionnaire was used to calculate 6- and 12-mo changes in CQI (categorized in quintiles), based on 4 criteria (total dietary fiber intake, glycemic index, whole grain/total grain ratio, and solid carbohydrate/total carbohydrate ratio). The outcomes were changes in intermediate markers of CVD.
During the 12-mo follow-up, the majority of participants improved their CQI by increasing their consumption of fruits, vegetables, legumes, fish, and nuts and decreasing their consumption of refined cereals, added sugars, and sugar-sweetened beverages. After 6 mo, body weight, waist circumference (WC), systolic and diastolic blood pressure (BP), fasting blood glucose, glycated hemoglobin (HbA1c), triglyceride levels, triglycerides and glucose (TyG) index, and TyG-WC decreased across successive quintiles of improvement in the CQI. After 12 mo, improvements were additionally observed for HDL cholesterol and for the ratio of total to HDL cholesterol. Favorable improvements (expressed in common units of SD and 95% CI) for quintile 5 compared with quintile 1 of CQI change were observed for most risk factors, including TyG-WC (SD −0.20; 95% CI −0.26, −0.15), HbA1c (SD −0.16; 95% CI −0.23, −0.10), weight (SD −0.12; 95% CI −0.14, −0.09), systolic BP (SD −0.11; 95% CI −0.19, −0.02) and diastolic BP (SD −0.11; 95% CI −0.19, −0.04).
Improvements in CQI were strongly associated with concurrent favorable CVD risk factor changes maintained over time in overweight/obese adults with MetS. This trial was registered as ISRCTN 89898870.
The carbohydrate-insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate ...diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m
were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal
) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal
) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d
less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d
less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate-insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108 .
Longer-term feeding studies suggest that a low-carbohydrate diet increases energy expenditure, consistent with the carbohydrate-insulin model of obesity. However, the validity of methodology utilized ...in these studies, involving doubly labeled water (DLW), has been questioned.
The aim of this study was to determine whether dietary energy requirement for weight-loss maintenance is higher on a low-compared with high-carbohydrate diet.
The study reports secondary outcomes from a feeding study in which the primary outcome was total energy expenditure (TEE). After attaining a mean Run-in weight loss of 10.5%, 164 adults (BMI ≤25 kg/m2 ; 70.1% women) were randomly assigned to Low-Carbohydrate (percentage of total energy from carbohydrate, fat, protein: 20/60/20), Moderate-Carbohydrate (40/40/20), or High-Carbohydrate (60/20/20) Test diets for 20 wk. Calorie content was adjusted to maintain individual body weight within ± 2 kg of the postweight-loss value. In analyses by intention-to-treat (ITT, completers, n = 148) and per protocol (PP, completers also achieving weight-loss maintenance, n = 110), we compared the estimated energy requirement (EER) from 10 to 20 wk of the Test diets using ANCOVA.
Mean EER was higher in the Low-versus High-Carbohydrate group in models of varying covariate structure involving ITT ranging from 181 (95% CI: 8–353) to 246 (64–427) kcal/d; P e0.04 and PP ranging from 245 (43–446) to 323 (122–525) kcal/d; P ≤0.02. This difference remained significant in sensitivity analyses accounting for change in adiposity and possible nonadherence.
Energy requirement was higher on a low- versus high-carbohydrate diet during weight-loss maintenance in adults, commensurate with TEE. These data are consistent with the carbohydrate-insulin model and lend qualified support for the validity of the DLW method with diets varying in macronutrient composition. This trial was registered at clinicaltrials.gov as NCT02068885.
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