Restriction of dietary carbohydrates, fat and/or protein is often used to reduce body weight and/or treat (metabolic) diseases. Since diet is a key modulator of the human gut microbiome, which plays an important role in health and disease, this review aims to provide an overview of current knowledge of the effects of macronutrient-restricted diets on gut microbial composition and metabolites. A structured search strategy was performed in several databases. After screening for inclusion and exclusion criteria, thirty-six articles could be included. Data are included in the results only when supported by at least three independent studies to enhance the reliability of our conclusions. Low-carbohydrate (<30 energy%) diets tended to induce a decrease in the relative abundance of several health-promoting bacteria, including Bifidobacterium, as well as a reduction in short-chain fatty acid (SCFA) levels in faeces. In contrast, low-fat diets (<30 energy%) increased alpha diversity, faecal SCFA levels and abundance of some beneficial bacteria, including Faecalibacterium prausnitzii. There were insufficient data to draw conclusions concerning the effects of low-protein (<10 energy%) diets on gut microbiota. Although the data of included studies unveil possible benefits of low-fat and potential drawbacks of low-carbohydrate diets for human gut microbiota, the diversity in study designs made it difficult to draw firm conclusions. Using a more uniform methodology in design, sample processing and sharing raw sequence data could foster our understanding of the effects of macronutrient restriction on gut microbiota composition and metabolic dynamics relevant to health. This systematic review was registered at https://www.crd.york.ac.uk/prospero as CRD42020156929.

A 60-d feeding trial was conducted to explore the potential regulatory effects of dietary Clostridium butyricum cultures (CBC) supplementation in high-carbohydrate diet (HCD) on carbohydrate utilisation, antioxidant capacity and intestinal microbiota of largemouth bass. Triplicate groups of largemouth bass (average weight 35·03 ± 0·04 g), with a destiny of twenty-eight individuals per tank, were fed low-carbohydrate diet and HCD supplemented with different concentration of CBC (0 %, 0·25 %, 0·50 % and 1·00 %). The results showed that dietary CBC inclusion alleviated the hepatic glycogen accumulation induced by HCD intake. Additionally, the expression of hepatic ampkα1 and insulin signaling pathway-related genes (ira, irb, irs, p13kr1 and akt1) increased linearly with dietary CBC inclusion, which might be associated with the activation of glycolysis-related genes (gk, pfkl and pk). Meanwhile, the expression of intestinal SCFA transport-related genes (ffar3 and mct1) was significantly increased with dietary CBC inclusion. In addition, the hepatic antioxidant capacity was improved with dietary CBC supplementation, as evidenced by linear decrease in malondialdehyde concentration and expression of keap1, and linear increase in antioxidant enzyme activities (total antioxidative capacity, total superoxide dismutase and catalase) and expression of antioxidant enzyme-related genes (nrf2, sod1, sod2 and cat). The analysis of bacterial 16S rRNA V3–4 region indicated that dietary CBC inclusion significantly reduced the enrichment of Firmicutes and potential pathogenic bacteria genus Mycoplasma but significantly elevated the relative abundance of Fusobacteria and Cetobacterium. In summary, dietary CBC inclusion improved carbohydrate utilization, antioxidant capacity and intestinal microbiota of largemouth bass fed HCD.

Previous studies have reported inconsistent associations between low-carbohydrate diets (LCD) and plasma lipid profile. Also, there is little evidence on the role of the quality and food sources of macronutrients in LCD in cardiometabolic health. We investigated the cross-sectional associations between LCD and plasma cardiometabolic risk markers in a nationwide representative sample of the US population. Diet was measured through two 24-h recalls. Overall, healthy (emphasising unsaturated fat, plant protein and less low-quality carbohydrates) and unhealthy (emphasising saturated fat, animal protein and less high-quality carbohydrate) LCD scores were developed according to the percentage of energy as total and subtypes of carbohydrate, protein and fat. Linear regression was used to estimate the percentage difference of plasma marker concentrations by LCD scores. A total of 34 785 participants aged 18–85 years were included. After adjusting for covariates including BMI, healthy LCD was associated with lower levels of insulin, homoeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP) and TAG, and higher levels of HDL-cholesterol, with the percentage differences (comparing extreme quartile of LCD score) of −5·91, −6·16, −9·13, −9·71 and 7·60 (all P trend < 0·001), respectively. Conversely, unhealthy LCD was associated with higher levels of insulin, HOMA-IR, CRP and LDL-cholesterol (all P trend < 0·001). Our results suggest that healthy LCD may have positive, whereas unhealthy LCD may have negative impacts on CRP and metabolic and lipid profiles. These findings underscore the need to carefully consider the quality and subtypes of macronutrients in future LCD studies.

Over the last several decades, there has been an increase in chronic diseases such as neurodegenerative, inflammatory, cardiovascular disease (CVD) and cancer. Two eating patterns, a low-carbohydrate diet (LCD) and fasting, have been researched independently over this period and found to be beneficial in reducing many of these chronic diseases’ detrimental effects. However, there have been limited studies about the synergy of these eating patterns. This current scoping review aims to explore the evidence of the health outcomes of using a LCD in conjunction with fasting. Four databases were searched, and fifteen articles were found that fit the inclusion criteria. The articles reported positive effects of combining the two eating patterns for type 2 diabetes, CVD, inflammatory conditions and weight reduction and maintenance. LCD and fasting together provide synergy in decreasing metabolic syndrome (as the key causes of chronic illnesses), such as insulin levels, fasting glucose, blood pressure, TAG and regulating lipid profile. Due to the paucity of research, further high-quality studies are needed to substantiate this evidence.

The percentage of US adults following low-carbohydrate diets (LCD) doubled in the last decade. Some researchers observed this trend with concern and highlighted the potential for nutritional deficiencies and impaired overall diet quality with LCD. The present study investigated nutrient intake in a nationally representative sample of 307 US adults following an LCD. Using cross-sectional data from the National Health and Nutrition Examination Surveys, we compared nutrient intake profiles in said individuals with the daily nutritional goals specified in the current 2020–2025 Dietary Guidelines for Americans (DGA). Results were then compared with the general population consuming a standard American diet. Almost 57 % of low-carbohydrate dieters were female, and the mean age was 48·67 (1·35) years. Individuals consuming LCD exceeded the recommendations for saturated fat, total lipid and sodium intake (both sexes). An insufficient intake was observed for fibre, Mg, potassium and several other vitamins (vitamins A, E, D in both sexes as well as vitamin C in men and folate in women). Neither men nor women met the recommendations for fibre intake. A comparable picture was found for the general population. The potentially insufficient intake of several essential nutrients in LCD warrants consideration and a careful assessment with regard to the current DGA.

There are two proven dietary approaches to shift type 2 diabetes (T2D) into remission: low-energy diets (LEDs) and low-carbohydrate diets (LCDs). These approaches differ in their rationale and application yet both involve carbohydrate restriction, either as an explicit goal or as a consequence of reducing overall energy intake. The aims of this systematic review were to identify, characterise and compare existing clinical trials that utilised ‘low-carbohydrate’ interventions with differing energy intakes. Electronic databases CENTRAL, CINAHL, Embase, MEDLINE and Scopus were searched to identify controlled clinical trials in adults with T2D involving low-carbohydrate intake (defined as <130 g carbohydrate/d) and reporting weight and glycaemic outcomes. The initial database search yielded 809 results, of which fifteen studies met the inclusion criteria. Nine out of fifteen studies utilised LCDs with moderate or unrestricted energy intake. Six trials utilised LEDs (<1200 kcal/d), with all except one incorporating meal replacements as part of a commercial weight loss programme. Interventions using both restricted and unrestricted (ad libitum) energy intakes produced clinically significant weight loss and reduction in glycated haemoglobin (HbA1c) at study endpoints. Trials that restricted energy intake were not superior to those that allowed ad libitum low-carbohydrate feeding at 12 and 24 months. An association was observed across studies between average weight loss and reduction in HbA1c at 6, 12 and 24 months, indicating that sustained weight loss is key to T2D remission. Further research is needed to specifically ascertain the weight-independent effects of carbohydrate restriction on glycaemic control in T2D.

Obesity remains a serious relevant public health concern throughout the world despite related countermeasures being well understood (i.e. mainly physical activity and an adjusted diet). Among different nutritional approaches, there is a growing interest in ketogenic diets (KD) to manipulate body mass (BM) and to enhance fat mass loss. KD reduce the daily amount of carbohydrate intake drastically. This results in increased fatty acid utilisation, leading to an increase in blood ketone bodies (acetoacetate, 3-β-hydroxybutyrate and acetone) and therefore metabolic ketosis. For many years, nutritional intervention studies have focused on reducing dietary fat with little or conflicting positive results over the long term. Moreover, current nutritional guidelines for athletes propose carbohydrate-based diets to augment muscular adaptations. This review discusses the physiological basis of KD and their effects on BM reduction and body composition improvements in sedentary individuals combined with different types of exercise (resistance training or endurance training) in individuals with obesity and athletes. Ultimately, we discuss the strengths and the weaknesses of these nutritional interventions together with precautionary measures that should be observed in both individuals with obesity and athletic populations. A literature search from 1921 to April 2021 using Medline, Google Scholar, PubMed, Web of Science, Scopus and Sportdiscus Databases was used to identify relevant studies. In summary, based on the current evidence, KD are an efficient method to reduce BM and body fat in both individuals with obesity and athletes. However, these positive impacts are mainly because of the appetite suppressive effects of KD, which can decrease daily energy intake. Therefore, KD do not have any superior benefits to non-KD in BM and body fat loss in individuals with obesity and athletic populations in an isoenergetic situation. In sedentary individuals with obesity, it seems that fat-free mass (FFM) changes appear to be as great, if not greater, than decreases following a low-fat diet. In terms of lean mass, it seems that following a KD can cause FFM loss in resistance-trained individuals. In contrast, the FFM-preserving effects of KD are more efficient in endurance-trained compared with resistance-trained individuals.

We aimed to examine the association between low-carbohydrate diet (LCD) scores during the first trimester and gestational diabetes mellitus (GDM) risk in a Chinese population. A total of 1455 women were included in 2017. Dietary information during the first trimester was collected by 24-h dietary recalls for 3 d. The overall, animal and plant LCD scores, which indicated adherence to different low-carbohydrate dietary patterns, were calculated. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 weeks gestation. Log-binomial models were used to estimate relative risks (RR) and 95 % CI. The results showed that the multivariable-adjusted RR of GDM from the lowest to the highest quartiles of the overall LCD score were 1·00 (reference), 1·15 (95 % CI 0·92, 1·42), 1·30 (95 % CI 1·06, 1·60) and 1·24 (95 % CI 1·01, 1·52) (P = 0·026 for trend). Multivariable-adjusted RR (95 % CI) of GDM from the lowest to the highest quartiles of the animal LCD score were 1·00 (reference), 1·20 (95 % CI 0·96, 1·50), 1·41 (95 % CI 1·14, 1·73) and 1·29 (95 % CI 1·04, 1·59) (P = 0·002 for trend). After additional adjustment for gestational weight gain before GDM diagnosis, the association of the overall LCD score with GDM risk was non-significant, while the association of animal LCD score with GDM risk remained significant. In conclusion, a low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of GDM in Chinese women.

Few studies have suggested that long-term adherence to low-carbohydrate diets (LCD) may affect maternal glucose metabolism in Western countries. We aimed to investigate the association between LCD during pregnancy and glucose metabolism in a Chinese population. A total of 1018 women in mid-pregnancy were recruited in 2017–2018. Participants underwent a 75 g oral glucose tolerance test (OGTT). Daily dietary intakes over the past month were accessed using a validated FFQ. The overall, animal and vegetable LCD scores which represent adherence to different low-carbohydrate dietary patterns were calculated. Mixed linear regression and generalised linear mixed regression were conducted to evaluate the associations between LCD scores and maternal glucose metabolism. Of the 1018 subjects, 194 (19·1 %) were diagnosed with gestational diabetes mellitus (GDM). The overall LCD score (β: 0·024, se 0·008, PFDR = 0·02) and animal LCD score (β: 0·023, se 0·008, PFDR = 0·02) were positively associated with OGTT 1-h glucose. No significant associations were found between the three different LCD scores with fasting plasma glucose, OGTT 2-h glucose, or insulin resistance, respectively. Compared with the lowest quartile, the crude OR of GDM for the highest quartile were 1·84 (95 % CI 1·14, 2·95) for overall LCD score (Pfor trend = 0·02) and 1·56 (95 % CI 1·00, 2·45) for animal LCD score (Pfor trend = 0·02). However, these associations became non-significant after adjustment for covariates. In conclusion, a low-carbohydrate dietary pattern with high animal protein and fat is associated with higher postprandial 1-h glucose levels in Chinese pregnant women.

Low-carbohydrate diets (LCD) have been promoted for weight control and type 2 diabetes (T2D) management, based on an emerging body of evidence, including meta-analyses with an indication of publication bias. Proposed definitions vary between 50 and 130 g/d, or <10 and <40 % of energy from carbohydrate, with no consensus on LCD compositional criteria. LCD are usually followed with limited consideration for other macronutrients in the overall diet composition, introducing variance in the constituent foods and in metabolic responses. For weight management, extensive evidence supports LCD as a valid weight loss treatment, up to 1–2 years. Solely lowering carbohydrate intake does not, in the medium/long term, reduce HbA1c for T2D prevention or treatment, as many mechanisms interplay. Under controlled feeding conditions, LCD are not physiologically or clinically superior to diets with higher carbohydrates for weight-loss, fat loss, energy expenditure or glycaemic outcomes; indeed, all metabolic improvements require weight loss. Long-term evidence also links the LCD pattern to increased CVD risks and mortality. LCD can lead to micronutrient deficiencies and increased LDL-cholesterol, depending on food selection to replace carbohydrates. Evidence is limited but promising regarding food choices/sources to replace high-carbohydrate foods that may alleviate the negative effects of LCD, demanding further insight into the dietary practice of medium to long term LCD followers. Long-term, high-quality studies of LCD with different food sources (animal and/or plant origins) are needed, aiming for clinical endpoints (T2D incidence and remission, cardiovascular events, mortality). Ensuring micronutrient adequacy by food selection or supplementation should be considered for people who wish to pursue long-term LCD.

The evidence linking low-carbohydrate diets (LCD) to CVD is controversial, and results from epidemiological studies are inconsistent. We aimed to assess the relationship between LCD patterns and coronary artery Ca (CAC) scores from computed tomography in the Multi-Ethnic Study of Atherosclerosis cohort. Our sample included 5614 men and women free of clinical CVD at baseline (2000–2002), who had a FFQ, a baseline measure and ≥1 measure of CAC during follow-up. We excluded those with implausible energy intake or daily physical activity. The overall, animal-based and plant-based LCD scores were calculated based on intakes of macronutrients. Relative risk regression and robust regression models were used to examine the cross-sectional and longitudinal relationship between LCD score quintile and CAC outcomes, after adjustment for multiple cardiovascular risk factors. The mean age of participants was 63 years. The median intakes of total carbohydrate, fat and protein were 53·7, 30·5 and 15·6 % energy/d, respectively. Among 2892 participants with zero CAC scores at baseline, 264 developed positive scores during 2·4-year follow-up (11–59 months). Among those with positive scores at baseline, the median increase in CAC was 47 units over the course of follow-up. The overall, the animal-based and the plant-based LCD scores were not associated with CAC prevalence, incidence and progression. In conclusion, diets low in carbohydrate and high in fat and/or protein, regardless of the sources of protein and fat, were not associated with higher levels of CAC, a validated predictor of cardiovascular events, in this large multi-ethnic cohort.

Keto analogues and amino acids (KAAA) supplementation can reduce blood ammonia concentrations in athletes undergoing high-intensity exercise under both ketogenic and thermoneutral conditions. This study evaluated the acute effects of KAAA supplementation on ammonia metabolism during extenuating endurance exercise in rats fed a ketogenic diet. In all, eighty male Fischer rats at 90 d of age were divided into eight groups, and some were trained using a swimming endurance protocol. A ketogenic diet supplemented with keto analogues was administered for 10 d. Administration of the ketogenic diet ended 3 d before the exhaustion test (extenuating endurance exercise). A ketogenic diet plus KAAA supplementation and extenuating endurance exercise (trained ketogenic diet supplemented with KAAA (TKKa)) increased blood ammonia concentrations by approximately 50 % compared with the control diet (trained control diet supplemented with KAAA (TCKa)) and similar training (effect size=1·33; statistical power=0·50). The KAAA supplementation reduced blood urea concentrations by 4 and 18 % in the control and ketogenic diet groups, respectively, compared with the groups fed the same diets without supplementation. The trained groups had 60 % lower blood urate concentrations after TCKa treatment than after TKKa treatment. Our results suggest that KAAA supplementation can reduce blood ammonia concentrations after extenuating endurance exercise in rats fed a balanced diet but not in rats fed a ketogenic diet.

Carbohydrate quantity and quality affect postprandial glucose response, glucose metabolism and risk of type 2 diabetes. The aim of this study was to examine the association of pre-pregnancy dietary carbohydrate quantity and quality with the risk of developing gestational diabetes mellitus (GDM). We used data from the Australian Longitudinal Study on Women’s Health that included 3607 women aged 25–30 years without diabetes who were followed up between 2003 and 2015. We examined carbohydrate quantity (total carbohydrate intake and a low-carbohydrate diet (LCD) score) and carbohydrate subtypes indicating quality (fibre, total sugar intake, glycaemic index, glycaemic load and intake of carbohydrate-rich food groups). Relative risks (RR) for development of GDM were estimated using multivariable regression models with generalised estimating equations. During 12 years of follow-up, 285 cases of GDM were documented in 6263 pregnancies (4·6 %). The LCD score, reflecting relatively high fat and protein intake and low carbohydrate intake, was positively associated with GDM risk (RR 1·54; 95 % CI 1·10, 2·15), highest quartile v. lowest quartile). Women in the quartile with highest fibre intake had a 33 % lower risk of GDM (RR 0·67; 95 % CI 0·45, 0·96)). Higher intakes of fruit (0·95 per 50 g/d; 95 % CI 0·90, 0·99) and fruit juice (0·89 per 100 g/d; 95 % CI 0·80, 1·00)) were inversely associated with GDM, whereas cereal intake was associated with a higher risk of GDM (RR 1·05 per 20 g/d; 95 % CI 1·01, 1·07)). Thus, a relatively low carbohydrate and high fat and protein intake may increase the risk of GDM, whereas higher fibre intake could decrease the risk of GDM. It is especially important to take the source of carbohydrates into account.

We aimed to clarify the effect of low-carbohydrate diet (LCD) on renal function in overweight and obese individuals without chronic kidney disease (CKD). Literature searches were performed using EMBASE, MEDLINE and Cochrane Library until December 2015. We selected articles that reported human studies from their inception until December 2015 in English using the following searching terms: ‘Low carbohydrate diet’ AND (‘Clinical trial’ OR ‘Clinical study’ OR ‘Clinical investigation’ OR ‘Observational study’ OR ‘Cohort study’). We compared the effects of LCD on renal function, defined as change in estimated glomerular filtration rate (eGFR), assessed in randomised-controlled trials. We calculated the mean change in eGFR and the mean change in standard deviations by eGFR or creatinine clearance, and compared the mean change in eGFR and standard deviations in LCD with those in the control diet using fixed-effects models. We selected nine randomised controlled trials including 1687 participants (861 were fed LCD and 826 were fed the control diet). The mean change in eGFR in the LCD group was −4·7 to 24·0 ml/min per 1·73 m2 and that in the control diet group was −4·1 to 10·8 ml/min per 1·73 m2. The mean change in eGFR in the LCD group was greater than that in the control diet (0·13 ml/min per 1·73 m2; 95 % CI 0·00, 0·26). In the present meta-analysis, we identified that the increase in eGFR was greater in LCD compared with the control diet in overweight and obese individuals without CKD.

Little is known about the potential adherence to and the effectiveness of a low-carbohydrate (LC) diet on weight loss and cardiometabolic risk factors in Chinese adults with a habitually high carbohydrate intake. In the present controlled feeding trial, fifty overweight or obese women (age 47·9 (sem 0·9) years; BMI 26·7 (sem 0·3) kg/m2) were randomly assigned to a LC non-energy-restricted diet (initial carbohydrate intake 20 g/d, with a 10 g increase weekly) or an energy-restricted (ER) diet (carbohydrate intake 156–205 g/d, ER to 5021 or 6276 kJ/d, 35 % average energy reduction) for 12 weeks. Over the intervention period, the two diets had comparable compliance (96 %) and self-reported acceptability. At week 12, carbohydrate intake in the LC and ER groups contributed to 36·1 and 51·1 % of total energy, respectively (P< 0·001). Although both diets showed similarly decreased mean body weight (LC − 5·27 (95 % CI − 6·08, − 4·46) kg; ER − 5·09 (95 % CI − 5·50, − 4·67) kg, P= 0·67) and percentage of fat mass measured by dual-energy X-ray absorptiometry (LC − 1·19 (95 % CI − 1·88, − 0·50) %; ER − 1·56 (95 % CI − 2·20, − 0·92) %, P= 0·42), participants in the LC group had greater reductions in the ratio of total cholesterol:HDL-cholesterol (P= 0·03) and also in the ratio of TAG:HDL-cholesterol (P= 0·01) than those in the ER group. The present 12-week diet trial suggested that both a LC non-energy-restricted diet and an ER diet were acceptable to Chinese women and both diets were equally effective in reducing weight and fat mass. Moreover, the LC diet showed beneficial effects on blood lipid profiles.

Our aim was to determine whether short-term weight loss on a low-carbohydrate/low-saturated fat diet improved endothelial function compared with a conventional high-carbohydrate diet, as this diet is expected to lower both blood glucose and LDL-cholesterol. In a randomised parallel design of two energy-restricted diets in an outpatient setting, thirty-six subjects (BMI 33 (sem 4) kg/m2) were randomised to a low- or high-carbohydrate diet both low in saturated fat. Flow-mediated dilatation (FMD), fasting glucose, insulin, lipids, adiponectin and adhesion molecules were measured at baseline, during weight loss and at 52 weeks. FMD did not change with either diet (5·2 (sem 0·6) to 5·5 (sem 0·6) %) despite weight loss of 5 % and significant reductions in glucose and insulin and LDL-cholesterol and was not different after sustained weight loss of 5 % at 52 weeks. Adiponectin fell by 6 % at 12 weeks (P = 0·1) with weight loss but rose by 17 % at 12 months (P < 0·05) with 5 % weight loss. There were no effects of diet. In contradistinction, adhesion molecules fell at 12 weeks, vascular cell adhesion molecule-1 by 14 % and intracellular adhesion molecule-1 by 13 % (both P < 0·05). There were correlations between change in adiponectin at 12 months and change in HDL (r 0·778, P < 0·01) and glucose (r − 0·563, P = 0·057). In summary, weight loss does not improve FMD. Novel cardiovascular risk factors improved at 12 weeks but the improvement in adiponectin was delayed.