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Acute Insulin Secretory Effects of a Classic Ketogenic Meal in Healthy Subjects: A Randomized Cross-Over Study.
Battezzati, A, Foppiani, A, Leone, A, De Amicis, R, Spadafranca, A, Mari, A, Bertoli, S
Nutrients. 2023;15(5)
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The ketogenic diet is a dietary regimen providing very low carbohydrate, high fat, and modest protein. Low carbohydrate and ketogenic diets have become increasingly popular in the treatment of metabolic syndrome, obesity, and type 2 diabetes. The main aim of this study was to measure the insulin secretory response to a typical ketogenic meal providing ~40% of individual energy needs and to compare it to the response to an isocaloric Mediterranean meal in healthy subjects. This study is a randomised cross-over study which enrolled twelve healthy subjects (50/50 female/male), adults with an age range of 19–31 years, and with a normal weight. The participants received mixed standardised meals of different compositions on two different days spaced apart by a washout period of 7 days. Each subject consumed two meals of identical energy content but differing in macronutrient composition. Results show that a Mediterranean meal accounting for 40% of daily dietary intake, requires, for its metabolism, the production of 7.8 ± 0.8 times the amount of insulin compared to fasting values, temporarily spiking the insulin secretory rate to 8.9 ± 1.2-fold the basal values. Authors conclude that a ketogenic meal is disposed of with only a minimal insulin secretory response compared to a Mediterranean meal.
Abstract
The classic ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics a starvation state with sufficient caloric intake to sustain growth and development. KD is an established treatment for several diseases, and it is currently evaluated in the management of insulin-resistant states, although insulin secretion after a classic ketogenic meal has never been investigated. We measured the insulin secretion to a ketogenic meal in 12 healthy subjects (50% females, age range 19-31 years, BMI range 19.7-24.7 kg/m2) after cross-over administrations of a Mediterranean meal and a ketogenic meal both satisfying ~40% of an individual's total energy requirement, in random order and separated by a 7-day washout period. Venous blood was sampled at baseline and at 10, 20, 30, 45, 60, 90, 120, and 180 min to measure glucose, insulin, and C-peptide concentrations. Insulin secretion was calculated from C-peptide deconvolution and normalized to the estimated body surface area. Glucose, insulin concentrations, and insulin secretory rate were markedly reduced after the ketogenic meal with respect to the Mediterranean meal: glucose AUC in the first OGTT hour -643 mg × dL-1 × min-1, 95% CI -1134, -152, p = 0.015; total insulin concentration -44,943 pmol/L, 95% CI -59,181, -3706, p < 0.001; peak rate of insulin secretion -535 pmol × min-1 × m-2, 95% CI -763, -308, p < 0.001. We have shown that a ketogenic meal is disposed of with only a minimal insulin secretory response compared to a Mediterranean meal. This finding may be of interest to patients with insulin resistance and or insulin secretory defects.
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High-fiber diet ameliorates gut microbiota, serum metabolism and emotional mood in type 2 diabetes patients.
Chen, L, Liu, B, Ren, L, Du, H, Fei, C, Qian, C, Li, B, Zhang, R, Liu, H, Li, Z, et al
Frontiers in cellular and infection microbiology. 2023;13:1069954
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Accumulating studies have demonstrated that there are strong correlations between type 2 diabetes mellitus (T2DM) and gut microbiota. A nutritious diet composed of an adequate level of dietary fibres could provide enough carbohydrates for the gut microbiota to ferment, and the microbial metabolites could provide energy supply and regulate the immune function of the host. The aim of this study was to analyse the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fibre diet. This study was a randomised, open-label, parallel-group clinical trial in T2DM patients with a 4-week treatment period. Seventeen patients clinically diagnosed with T2DM enrolled in the clinical trial and were randomly assigned into two groups: the control group (n = 8) or the intervention group (n = 9). Results showed that the high-fibre diet (compared to the control group): - improved glucose homeostasis and lipid metabolism of participants with T2DM; - decreased serum levels of inflammatory chemokines in participants with T2DM; - alleviated depression and anxiety symptoms, particularly by the uptake of more diverse carbohydrates in the diet in participants with T2DM; - enhanced the diversity of gut microbiota in the treatment group. Authors conclude that the dietary source of fibre demonstrated protective impacts on the gut ecosystem, and the alteration of the gut microbiota composition improved the glucose homeostasis in patients with T2DM.
Abstract
Previous studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) often had the problems of fecal microbiota dysbiosis, and were usually accompanied with psychiatric comorbidities (such as depression and anxiety). Here, we conducted a randomized clinical study to analyze the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fiber diet. The glucose homeostasis of participants with T2DM was improved by the high-fiber diet, and the serum metabolome, systemic inflammation and psychiatric comorbidities were also altered. The increased abundances of Lactobacillus, Bifidobacterium and Akkermansias revealed that the proportions of beneficial gut microbes were enriched by the high-fiber diet, while the abundances of Desulfovibrio, Klebsiella and other opportunistic pathogens were decreased. Therefore, the current study demonstrated that the intestinal microbiota alterations which were influenced by the high-fiber diet could improve the serum metabolism and emotional mood of patients with T2DM.
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Do Dietary Supplements Affect Inflammation, Oxidative Stress, and Antioxidant Status in Adults with Hypothyroidism or Hashimoto's Disease?-A Systematic Review of Controlled Trials.
Kubiak, K, Szmidt, MK, Kaluza, J, Zylka, A, Sicinska, E
Antioxidants (Basel, Switzerland). 2023;12(10)
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A deficiency of the thyroid hormone causes hypothyroidism (HT), whereas Autoimmune thyroiditis (AIT) is mainly an organ-specific autoimmune condition. Both HT and AIT are characterised by low-grade inflammation and inflammation in the thyroid gland. Dietary supplements may offer health benefits; however, previous research findings are inconclusive. This systematic review evaluated twenty-two controlled studies to understand the effectiveness of dietary supplements in reducing inflammation and oxidative stress and improving antioxidant and thyroid parameters in patients with HT or AIT. The efficacy of dietary supplements in improving thyroid health and reducing inflammation and oxidative stress was inconclusive due to the low quality of the included studies and the limited number of available studies. Selenium supplements might be beneficial in improving thyroid parameters and inflammation in patients with HT or AIT. Even though the therapeutic benefits of dietary supplements in treating thyroid disease were inconclusive, healthcare professionals can use them to address the common nutritional deficiencies in people with HT and AIT. Further, large, long-term, robust studies are required to assess the therapeutic utility of different dietary supplements in promoting the health of the thyroid gland.
Abstract
This systematic review aims to summarise the results of controlled trials on dietary supplements (DS) usage and inflammation, oxidative stress, antioxidant status, and thyroid parameter improvement in hypothyroidism (HT)/Hashimoto's thyroiditis (AIT) patients. The study protocol was registered with PROSPERO (no. CRD42022365149). A comprehensive search of the PubMed, Scopus, and Web of Science databases resulted in the identification of nineteen randomised controlled trials and three non-randomised studies for the review; three studies examined the effect of supplementation with vitamin D, twelve studies-with selenium, and seven studies-with other DS. Based on very limited evidence, the lack of influence of vitamin D supplementation on inflammatory parameters was found, while no studies have examined oxidative stress and antioxidant status parameters, and only one provided results for a single thyroid parameter after an intervention. Some evidence was found proving that selenium supplementation may decrease inflammation and improve thyroid parameters, but reaching a conclusion about its influence on oxidative stress and antioxidant status is not possible because of the insufficient number of studies. Additionally, due to examining other DS (e.g., multicomponent, Nigella sativa, and genistein) only in single studies, conclusions cannot be drawn. Further long-term, high-quality randomised controlled trials are necessary to better understand the influence of DS on inflammation, oxidative stress, and antioxidant status, as well as their potential to improve thyroid gland function in HT/AIT patients.
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The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines.
Kelishadi, MR, Naeini, AA, Khorvash, F, Askari, G, Heidari, Z
Scientific reports. 2022;12(1):271
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Migraine and headaches can be a seriously debilitating disorder for those who suffer from them. The exact cause is still unknown; however, it is thought that inflammation in the body and the blood vessels which serve the brain may be part of the problem. Alpha-lipoic acid (ALA) is a nutrient that is found in foods such as broccoli and organ meats and it is also produced within the body. It has been shown to have anti-inflammatory effects and therefore may be of benefit to those individuals who have headaches and migraines. This 12-week randomised control study of 92 individuals with migraine aimed to determine the effects of ALA supplementation on measures of inflammation in the blood vessels and symptoms. The results showed that oxygen passage to the brain was improved, which resulted in an improvement to migraine severity and frequency. It was concluded that ALA supplementation could be considered a possible migraine treatment in conjunction with regular pain medications for migraine symptoms. This study could be used by healthcare professionals to recommend the consumption of ALA as part of migraine management.
Abstract
The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (- 6.45 ± 0.82 mg/dl vs - 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (- 2.02 ± 0.30 ng/ml vs - 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P < 0.001), frequency (P = 0.001), headache impact test (HIT-6) (P < 0.001), headache dairy results (HDR) (P = 0.003), and migraine headache index score (MHIS) (P < 0.001) had significantly decreased in the intervention as compared to the control group. No significant changes were observed for NO levels and duration of migraine pains. ALA supplementation can be considered a potential adjunct treatment in patients with migraine due to its improving mitochondrial and endothelial functions and clinical symptoms.
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A Hot Water Extract of Curcuma longa L. Improves Fasting Serum Glucose Levels in Participants with Low-Grade Inflammation: Reanalysis of Data from Two Randomized, Double-Blind, Placebo-Controlled Trials.
Uchio, R, Okuda-Hanafusa, C, Saji, R, Kawasaki, K, Muroyama, K, Murosaki, S, Yamamoto, Y, Hirose, Y
Nutrients. 2022;14(18)
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Chronic low-grade inflammation plays a significant role in the development of type 2 diabetes. The hot water extract of turmeric (Curcuma longa L.) has been shown to have anti-inflammatory and antioxidant properties, as well as the ability to lower blood glucose levels in animal models. Curcuma longa L. extract may improve systemic glucose levels by reducing insulin resistance and pancreatic β-cell dysfunction. In this study, the results from two randomised, double-blind, placebo-controlled trials were reanalysed to assess the effects of hot water extract of C. longa on serum glucose levels in overweight individuals with low-grade inflammation. When compared to the placebo group, participants in the Curcuma longa L. group with high hs-CRP levels showed significant improvements in serum hs-CRP levels and fasting blood glucose levels. Healthcare professionals can use the results of this study to understand the potential beneficial effects of Curcuma longa L. extract on systemic glucose regulation in overweight individuals with low-grade inflammation. Further robust research is needed to investigate the effect of Curcuma longa L. extract on reducing proinflammatory cytokines and suppressing the activation of the NF-kB signalling pathway.
Abstract
The dietary spice Curcuma longa L. (C. longa), also known as turmeric, has various biological effects. A hot water extract of C. longa was shown to have anti-inflammatory activities in preclinical and clinical studies. Chronic low-grade inflammation is associated with the disruption of glucose homeostasis, but the effect of C. longa extract on glucose metabolism in humans is poorly understood. Therefore, we investigated the effect of C. longa extracts on serum glucose levels in the presence of low-grade inflammation. We reanalyzed our published data from two randomized, double-blind, placebo-controlled trials in overweight participants aged 50 to 69 years and performed a stratified analysis using the inflammatory marker high-sensitivity C-reactive protein (hsCRP). In both studies, participants took a test food with a hot water extract of C. longa (C. longa extract group, n = 45 per study) or without C. longa extract (placebo group, n = 45 per study) daily for 12 weeks, and we measured the levels of serum hsCRP and fasting serum glucose. The mean baseline hsCRP value was used to stratify participants into two subgroups: a low-hsCRP subgroup (baseline mean hsCRP < 0.098 mg/dL) and a high-hsCRP subgroup (baseline mean hsCRP ≥ 0.098 mg/dL). In the low-hsCRP subgroup, we found no significant difference in fasting serum glucose levels between the two groups in either study, but in the high-hsCRP subgroup, the C. longa extract group had significantly lower levels of serum hsCRP (p < 0.05) and fasting serum glucose (p < 0.05) than the placebo group in both studies. In conclusion, a hot water extract of C. longa may help to improve systemic glucose metabolism in people with chronic low-grade inflammation.
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Buckwheat and Cardiometabolic Health: A Systematic Review and Meta-Analysis.
Llanaj, E, Ahanchi, NS, Dizdari, H, Taneri, PE, Niehot, CD, Wehrli, F, Khatami, F, Raeisi-Dehkordi, H, Kastrati, L, Bano, A, et al
Journal of personalized medicine. 2022;12(12)
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Buckwheat is a gluten-free, pseudo-grain rich in bioactive compounds that are cardiometabolic health protective. Bioactive cardioprotective compounds include proteins, fibre, and polyphenols such as rutin and quercetin-3-glucoside. This systematic review and meta-analysis investigated the supplementation and consumption of buckwheat and its effects on cardiovascular risk markers. Sixteen studies were included in the systematic review, and ten were included in the meta-analysis. This systematic review and meta-analysis showed a modest, non-significant improvement in total cholesterol and glucose levels. Further robust studies are required to investigate the beneficial effects of bioactive compounds found in buckwheat due to the high heterogeneity of the included studies and the poor quality of the included studies. However, healthcare professionals can use the results of this research to understand the potential of buckwheat in improving or maintaining cardiometabolic health.
Abstract
Buckwheat (BW) is suggested to have beneficial effects, but evidence on how it affects cardiometabolic health (CMH) is not yet established. We aimed to assess the effects of BW and/or its related bioactive compounds on cardiovascular disease (CVD) risk markers in adults. Five databases were searched for eligible studies. Observational prospective studies, nonrandomized or randomized trials were considered if they assessed BW, rutin or quercetin-3-glucoside intake and CVD risk markers. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting. We selected 16 human studies based on 831 subjects with mild metabolic disturbances, such as hypercholesterolemia, diabetes and/or overweight. Eight studies, investigating primarily grain components, were included in the meta-analyses (n = 464). High study heterogeneity was present across most of our analyses. Weighted mean difference (WMD) for subjects receiving BW supplementation, compared to controls, were - 0.14 mmol/L (95% CI: -0.30; 0.02) for total cholesterol (TC), -0.03 mmol/L (95% CI: -0.22; 0.16) for LDL cholesterol, -0.14 kg (95% CI: -1.50; 1.22) for body weight, -0.04 mmol/L (95% CI: - 0.09;0.02) for HDL cholesterol, -0.02 mmol/L (95% CI: -0.15; 0.11) for triglycerides and -0.18 mmol/L (95% CI: -0.36; 0.003) for glucose. Most of the studies (66.7%) had concerns of risk of bias. Studies investigating other CVD markers were scarce and with inconsistent findings, where available. Evidence on how BW affects CMH is limited. However, the available literature indicates that BW supplementation in mild dyslipidaemia and type 2 diabetes may provide some benefit in lowering TC and glucose, albeit non-significant. Our work highlights the need for more rigorous trials, with better methodological rigor to clarify remaining uncertainties on potential effects of BW on CMH and its utility in clinical nutrition practice.
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Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action.
Gouveia, HJCB, Urquiza-Martínez, MV, Manhães-de-Castro, R, Costa-de-Santana, BJR, Villarreal, JP, Mercado-Camargo, R, Torner, L, de Souza Aquino, J, Toscano, AE, Guzmán-Quevedo, O
International journal of molecular sciences. 2022;23(15)
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Metabolic syndrome is a condition characterised by at least three of the five risk factors, such as abdominal obesity, elevated fasting glucose, blood pressure and triglycerides and reduced high-density lipoprotein cholesterol (HDL-c). There is a strong link between metabolic syndrome and the development of cardiovascular disease and Type 2 diabetes. Research suggests that increasing consumption of flavonoid-rich foods can be beneficial in reducing cardiovascular morbidity and mortality. Flavonoids are bioactive compounds that possess antioxidative, anti-inflammatory, anti-cancerous, anti-mutagenic, and enzymatic properties. This systematic review of 29 randomised controlled trials evaluated the beneficial effects of long-term flavonoid supplementation in reducing the risk factors of metabolic syndrome. This review included a variety of flavonoid supplements, such as anthocyanin, hesperidin, quercetin, epigallocatechin gallate (egcg), genistein, theaflavin, catechin, and eriocitrin. Additionally, this research investigated the mechanisms behind the beneficial effects of flavonoid supplementation. Results showed that flavonoid supplementation for at least three weeks improved metabolic parameters and inflammatory markers, with hesperidin showing the greatest improvements in metabolic parameters. Healthcare professionals can use these findings to understand the potential benefits of long-term flavonoid supplementation in improving metabolic parameters. However, more robust studies are needed to determine the therapeutic dosages of different flavonoids.
Abstract
Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.
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The Effect of Ketogenic Diet on Shared Risk Factors of Cardiovascular Disease and Cancer.
Mohammadifard, N, Haghighatdoost, F, Rahimlou, M, Rodrigues, APS, Gaskarei, MK, Okhovat, P, de Oliveira, C, Silveira, EA, Sarrafzadegan, N
Nutrients. 2022;14(17)
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Cardiovascular disease and cancer are major causes of mortality worldwide and share common pathophysiological mechanisms and risk factors. The ketogenic diet, a low-carbohydrate and high-fat diet, may alter metabolic pathways, potentially lowering the risk of developing these diseases. Specifically, the ketogenic diet improves energy metabolism by promoting the use of body ketones for energy production. This review examines the protective effects of the ketogenic diet in reducing cardiovascular disease and cancer risk and explores the underlying mechanisms. The ketogenic diet may suppress oxidative stress and inflammation while improving common risk factors such as obesity, hypertension, diabetes, and dyslipidaemia. It is important to conduct further rigorous studies to assess the long-term effects of the ketogenic diet. However, healthcare professionals can use these findings to understand the short-term benefits of the diet in managing metabolic abnormalities and reducing the risk of developing cardiovascular disease and cancer.
Abstract
Cardiovascular disease (CVD) and cancer are the first and second leading causes of death worldwide, respectively. Epidemiological evidence has demonstrated that the incidence of cancer is elevated in patients with CVD and vice versa. However, these conditions are usually regarded as separate events despite the presence of shared risk factors between both conditions, such as metabolic abnormalities and lifestyle. Cohort studies suggested that controlling for CVD risk factors may have an impact on cancer incidence. Therefore, it could be concluded that interventions that improve CVD and cancer shared risk factors may potentially be effective in preventing and treating both diseases. The ketogenic diet (KD), a low-carbohydrate and high-fat diet, has been widely prescribed in weight loss programs for metabolic abnormalities. Furthermore, recent research has investigated the effects of KD on the treatment of numerous diseases, including CVD and cancer, due to its role in promoting ketolysis, ketogenesis, and modifying many other metabolic pathways with potential favorable health effects. However, there is still great debate regarding prescribing KD in patients either with CVD or cancer. Considering the number of studies on this topic, there is a clear need to summarize potential mechanisms through which KD can improve cardiovascular health and control cell proliferation. In this review, we explained the history of KD, its types, and physiological effects and discussed how it could play a role in CVD and cancer treatment and prevention.
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Effects of Nutrition Intervention on Blood Glucose, Body Composition, and Phase Angle in Obese and Overweight Patients with Diabetic Foot Ulcers.
Basiri, R, Spicer, MT, Ledermann, T, Arjmandi, BH
Nutrients. 2022;14(17)
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Diabetic foot ulcers (DFUs) are among the most common complications of uncontrolled diabetes. Nutrition can play a key role in the prevention and improvement of the clinical outcomes of DFUs. The aim of this study was to examine the effects of nutrition education and supplementation on long-term blood glucose control, body composition, and phase angle as an indicator of cellular health and cell membrane integrity in patients with DFUs. This study is a randomised clinical trial in which participants were randomly assigned to either the treatment group (nutritional supplements, diet education, and standard care) or the control group (standard care). Results show that supplementing the diet with extra energy sources and nutrients did not have any negative effects on long-term blood glucose control or the body composition of overweight and obese patients with DFUs when combined with nutrition education. Additionally, the nutrition intervention had some positive effects on the body composition and phase angle of DFU patients in the treatment group. Authors conclude that dietary recommendations for overweight and obese individuals with DFUs should prioritise proper wound healing by recommending that patients consume adequate energy sources and essential nutrients.
Abstract
Nutrition can play an important role in the treatment of chronic wounds such as diabetic foot ulcers (DFUs); however, diet therapy is not currently part of the standard care for DFUs. There are numerous controversies about dietary recommendations, especially regarding calories and macronutrients, for overweight and obese patients with DFUs. This study examined the effects of nutrition education and supplementation on body composition in overweight and obese patients with DFUs. Twenty-nine patients with DFUs between the ages of 30 and 70 years were randomly assigned to either the treatment group (nutritional supplements, diet education, and standard care) or the control group (standard care). At baseline, the mean body mass index (BMI) was 33.5 kg/m2 for the treatment group and 34.1 kg/m2 for the control group. HbA1c decreased in both groups, with no significant difference between the groups. On average, patients in the treatment group lost less lean body mass and gained less fat than the control group ((3.8 kg vs. 4.9 kg) and (0.9 kg vs. 3.6 kg), respectively). While the interaction between group and time did not reach statistical significance for any of the study variables after adjustments for confounding variables, the observed changes are clinically relevant.
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Therapeutic Effects of Butyrate on Pediatric Obesity: A Randomized Clinical Trial.
Coppola, S, Nocerino, R, Paparo, L, Bedogni, G, Calignano, A, Di Scala, C, de Giovanni di Santa Severina, AF, De Filippis, F, Ercolini, D, Berni Canani, R
JAMA network open. 2022;5(12):e2244912
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Gut microbiome (GM) could play a role in obesity. A metabolically healthy GM is maintained by a diet rich in fibre. Plant foods are fermented by the gut microbiome to produce the antiobesogenic short-chain fatty acid butyrate. The aim of this study was to evaluate whether butyrate supplementation can be effective in paediatric obesity treatment. This study was a randomised, quadruple-blind, parallel-group, placebo-controlled trial. Children were randomly assigned to the treatment group or placebo in a 1:1 ratio. Results showed that in children with obesity, oral butyrate supplementation produced a reduction of body mass index and exerted beneficial effects on glucose metabolism and inflammation. In fact, butyrate supplementation decreased homeostatic model assessment of insulin resistance [HOMA-IR] and fasting insulin levels in children with obesity. Additionally, the GM analysis supported the role of butyrate in glucose metabolism, as suggested by a more positive response in children with a higher abundance of butyrate-producing bacteria at baseline. Authors conclude that their findings support the importance of the GM-derived metabolite butyrate as a protective factor against obesity, highlighting the central role of a healthy diet and GM function to achieve an optimal endogenous production of butyrate.
Abstract
IMPORTANCE The pediatric obesity disease burden imposes the necessity of new effective strategies. OBJECTIVE To determine whether oral butyrate supplementation as an adjunct to standard care is effective in the treatment of pediatric obesity. DESIGN, SETTING, AND PARTICIPANTS A randomized, quadruple-blind, placebo-controlled trial was performed from November 1, 2020, to December 31, 2021, at the Tertiary Center for Pediatric Nutrition, Department of Translational Medical Science, University of Naples Federico II, Naples, Italy. Participants included children aged 5 to 17 years with body mass index (BMI) greater than the 95th percentile. INTERVENTIONS Standard care for pediatric obesity supplemented with oral sodium butyrate, 20 mg/kg body weight per day, or placebo for 6 months was administered. MAIN OUTCOMES AND MEASURES The main outcome was the decrease of at least 0.25 BMI SD scores at 6 months. The secondary outcomes were changes in waist circumference; fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, ghrelin, microRNA-221, and interleukin-6 levels; homeostatic model assessment of insulin resistance (HOMA-IR); dietary and lifestyle habits; and gut microbiome structure. Intention-to-treat analysis was conducted. RESULTS Fifty-four children with obesity (31 girls [57%], mean [SD] age, 11 [2.91] years) were randomized into the butyrate and placebo groups; 4 were lost to follow-up after receiving the intervention in the butyrate group and 2 in the placebo group. At intention-to-treat analysis (n = 54), children treated with butyrate had a higher rate of BMI decrease greater than or equal to 0.25 SD scores at 6 months (96% vs 56%, absolute benefit increase, 40%; 95% CI, 21% to 61%; P < .01). At per-protocol analysis (n = 48), the butyrate group showed the following changes as compared with the placebo group: waist circumference, -5.07 cm (95% CI, -7.68 to -2.46 cm; P < .001); insulin level, -5.41 μU/mL (95% CI, -10.49 to -0.34 μU/mL; P = .03); HOMA-IR, -1.14 (95% CI, -2.13 to -0.15; P = .02); ghrelin level, -47.89 μg/mL (95% CI, -91.80 to -3.98 μg/mL; P < .001); microRNA221 relative expression, -2.17 (95% CI, -3.35 to -0.99; P < .001); and IL-6 level, -4.81 pg/mL (95% CI, -7.74 to -1.88 pg/mL; P < .001). Similar patterns of adherence to standard care were observed in the 2 groups. Baseline gut microbiome signatures predictable of the therapeutic response were identified. Adverse effects included transient mild nausea and headache reported by 2 patients during the first month of butyrate intervention. CONCLUSIONS AND RELEVANCE Oral butyrate supplementation may be effective in the treatment of pediatric obesity. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04620057.