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Impact of wheat aleurone on biomarkers of cardiovascular disease, gut microbiota and metabolites in adults with high body mass index: a double-blind, placebo-controlled, randomized clinical trial.
Fava, F, Ulaszewska, MM, Scholz, M, Stanstrup, J, Nissen, L, Mattivi, F, Vermeiren, J, Bosscher, D, Pedrolli, C, Tuohy, KM
European journal of nutrition. 2022;61(5):2651-2671
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Cross-sectional studies have shown that whole grain cereal consumption can reduce the risk of cardiovascular disease (CVD, as well as reduce systemic inflammation, which is linked to many chronic diet associated diseases. Aleurone is a wheat grain fraction composed of a single cell layer that constitutes the outermost portion of the endosperm and contains many of the beneficial substances. The primary aim of this study was to investigate the effect of aleurone consumption on plasma homocysteine concentrations in overweight/ obese subjects. Secondary aim was to measure the impact of chronic aleurone supplementation on markers of CVD risk and on the human gut microbiota and its metabolic output. This study is a placebo-controlled, randomised, double-blind parallel trial with 2 test foods, wheat aleurone-rich foods or placebo foods (cellulose). Participants (n=74) were randomised to receive the active supplementation (aleurone 27 g per day) or placebo for 4 consecutive weeks. Results show that although average plasma homocysteine levels decreased upon wheat aleurone supplementation treatment, this change was not statistically significant, and homocysteine levels did not differ between groups after intervention. Furthermore, there was a significant increase in bifidobacteria both over time and compared to the placebo. Several significant and useful biomarkers of wheat aleurone intake, all related to wheat polyphenol metabolism by the gut microbiota, were identified. Authors conclude that wheat aleurone supplementation has the potential to modulate the gut microbial metabolic output and increase faecal bifidobacterial abundance, but it does not impact plasma homocysteine or other CVD biomarkers.
Abstract
PURPOSE Aleurone is a cereal bran fraction containing a variety of beneficial nutrients including polyphenols, fibers, minerals and vitamins. Animal and human studies support the beneficial role of aleurone consumption in reducing cardiovascular disease (CVD) risk. Gut microbiota fiber fermentation, polyphenol metabolism and betaine/choline metabolism may in part contribute to the physiological effects of aleurone. As primary objective, this study evaluated whether wheat aleurone supplemented foods could modify plasma homocysteine. Secondary objectives included changes in CVD biomarkers, fecal microbiota composition and plasma/urine metabolite profiles. METHODS A parallel double-blind, placebo-controlled and randomized trial was carried out in two groups of obese/overweight subjects, matched for age, BMI and gender, consuming foods supplemented with either aleurone (27 g/day) (AL, n = 34) or cellulose (placebo treatment, PL, n = 33) for 4 weeks. RESULTS No significant changes in plasma homocysteine or other clinical markers were observed with either treatment. Dietary fiber intake increased after AL and PL, animal protein intake increased after PL treatment. We observed a significant increase in fecal Bifidobacterium spp with AL and Lactobacillus spp with both AL and PL, but overall fecal microbiota community structure changed little according to 16S rRNA metataxonomics. Metabolomics implicated microbial metabolism of aleurone polyphenols and revealed distinctive biomarkers of AL treatment, including alkylresorcinol, cinnamic, benzoic and ferulic acids, folic acid, fatty acids, benzoxazinoid and roasted aroma related metabolites. Correlation analysis highlighted bacterial genera potentially linked to urinary compounds derived from aleurone metabolism and clinical parameters. CONCLUSIONS Aleurone has potential to modulate the gut microbial metabolic output and increase fecal bifidobacterial abundance. However, in this study, aleurone did not impact on plasma homocysteine or other CVD biomarkers. TRIAL REGISTRATION The study was registered at ClinicalTrials.gov (NCT02067026) on the 17th February 2014.
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The effect of periodic ketogenic diet on newly diagnosed overweight or obese patients with type 2 diabetes.
Li, S, Lin, G, Chen, J, Chen, Z, Xu, F, Zhu, F, Zhang, J, Yuan, S
BMC endocrine disorders. 2022;22(1):34
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Currently, the ketogenic diet is gaining popularity in managing Type 2 diabetes (T2D). Ketogenic diets replace carbohydrates with fat and include limited carbohydrates and adequate protein. This randomised controlled trial evaluated the effects of the 12-week ketogenic diet on sixty overweight or obese T2D patients. Both the ketogenic and control diabetes diet groups achieved significant reductions in weight, body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting blood glucose, fasting insulin, and HbA1c. However, the ketogenic group showed significantly greater reductions in body mass, blood lipids, and blood glucose than the control group. In the ketogenic diet group, serum uric acid levels were higher than those in the control diet group. It was found that the control diet group adhered to the diet for a longer period than the ketogenic diet group, whose willingness to adhere to the diet long-term was weaker. More robust long-term studies are needed to evaluate the long-term effects of a ketogenic diet. In this study, more patients who followed the ketogenic diet experienced hypoglycaemic events during the first four weeks. Healthcare providers should exercise caution when recommending a short term therapeutic ketogenic diet.
Abstract
BACKGROUND The ketogenic diet (KD) is characterized by fat as a substitute of carbohydrates for the primary energy source. There is a large number of overweight or obese people with type 2 diabetes mellitus (T2DM), while this study aims to observe periodic ketogenic diet for effect on overweight or obese patients newly diagnosed as T2DM. METHODS A total of 60 overweight or obese patients newly diagnosed as T2DM were randomized into two groups: KD group, which was given ketogenic diet, and control group, which was given routine diet for diabetes, 30 cases in each group. Both dietary patterns lasted 12 weeks, and during the period, the blood glucose, blood lipid, body weight, insulin, and uric acid before and after intervention, as well as the significance for relevant changes, were observed. RESULTS For both groups, the weight, BMI(body mass index), Waist, TG (triglyceride), TC(cholesterol), LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), FBG (fasting glucose), FINS (fasting insulin), HbA1c (glycosylated hemoglobin) were decreased after intervention (P < 0.05), while the decrease rates in the KD group was more significant than the control group. However, UA(serum uric acid) in the KD group showed an upward trend, while in the control group was not changed significantly (P > 0.05).The willingness to adhere to the ketogenic diet over the long term was weaker than to the routine diet for diabetes. CONCLUSION Among the overweight or obese patients newly diagnosed as type 2 diabetes mellitus, periodic ketogenic diet can not only control the body weight, but also control blood glucose and lipid, but long-term persistence is difficult.
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Impact of changes in physical activity or BMI on risk of heart failure in women - the prospective population study of women in Gothenburg.
Halldin, AK, Lissner, L, Lernfelt, B, Björkelund, C
Scandinavian journal of primary health care. 2020;38(1):56-65
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Heart failure (HF) is a severe and progressive condition with poor prognosis. Obesity is a risk factor for HF. The aim of this study was to investigate the impact of change in physical activity or change in body mass index on the risk of later developing HF in women without a previous diagnosis of HF. This study is prospective longitudinal study which includes 1749 healthy women from the Prospective Population Study of Women in Gothenburg. Results indicate that gaining weight in early middle age is more harmful than gaining weight later in life, with regard to the risk of developing HF later in life. Furthermore, reduced risk of future HF in healthy women may be achieved by remaining physically active from young middle age and throughout life or by increasing the level of physical activity. Authors conclude that the role of physical activity in preventing the development of obesity must be taken into account.
Abstract
Objective: To longitudinally evaluate the impact of change in physical activity or change in body mass index (BMI) over time on the risk of developing heart failure (HF) in women without a previous diagnosis of HF.Design and setting: Longitudinal, observational, prospective study of women in Gothenburg, Sweden. Data on BMI and level of physical activity were collected from examinations 1968-1992 and hospital diagnoses and mortality data were ascertained from 1980 to 2012.Subjects: Data were obtained from 1749 women included in the Prospective Population Study of Women in Gothenburg.Main outcome measures: Hazard ratio (HR) for HF was calculated, using a Cox regression model.Results: Women with stable high physical activity during 1968-1980 and 1980-1992 reduced their risk of subsequent HF compared to the non-active women (for 1968-1980 HR 0.66, 95% Confidence Interval (CI) 0.44-0.99 and for 1980-1992 HR 0.47, 95% CI 0.29-0.74). Women with increasing levels of physical activity during 1980-1992 reduced their risk of HF compared to the non-active women (HR 0.40, 95% CI 0.22-0.72). Increase in BMI from overweight to obesity during 1968-1980 predicted increased risk of developing HF (HR 1.93, 95% CI 1.18-3.14).Conclusions: Reduced risk of future HF in healthy women may be achieved by remaining physically active from young middle age and throughout life or by increasing the level of physical activity. This is particularly important for sedentary women in middle age. The role of physical activity in preventing the development of obesity must be taken into account.Key pointsA sedentary lifestyle and obesity are risk factors for developing heart failure (HF) in women.The risk of developing HF may be reduced by increasing the level of activity in sedentary middle-aged women.For younger women, avoiding obesity is most important to reduce the risk of later HF.Primary care has a key role in guiding women towards the most effective lifestyle changes to prevent development of HF.
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Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis.
Di Palo, DM, Garruti, G, Di Ciaula, A, Molina-Molina, E, Shanmugam, H, De Angelis, M, Portincasa, P
Nutrients. 2020;12(2)
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Intestinal permeability (IP) is dependent on the structure and function of the intestinal barrier. The gut barrier integrity is the result of ongoing equilibrium and crosstalk involving the microbiome, the mucus, the enterocytes [intestinal absorptive cells], the gut immune system, and the gut–vascular barrier. The main aim of this study was to explore the pan-enteric IP (stomach, small intestine, and colon) with respect to size and fat distribution, as well as the presence of liver steatosis. The study is a cohort study that examined 120 subjects (obese n = 45, overweight n=30, normal weight n = 45). Groups were gender-matched except for the prevalence of males in the overweight group. Results highlight the existence of an association between colonic (but not stomach and small intestinal) permeability, obesity, and liver steatosis. Findings show that: - liver steatosis was detected in 69 (57.5%) subjects, of which 36 (52%) were males. The prevalence of liver steatosis increased from 4% in normal weight subjects to 77%, and to 98% in overweight and obese subjects, respectively. - gastrointestinal permeability changed between age groups at every tract, whereas stomach and small intestine IP decreased with age. Furthermore, this finding also occurred in subjects aged over or equal to 65 years, with respect to colonic permeability. Authors conclude that further studies must evaluate the possibility of modulating colonic permeability to allow both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.
Abstract
Intestinal permeability (IP) is essential in maintaining gut-metabolic functions in health. An unequivocal evaluation of IP, as marker of intestinal barrier integrity, however, is missing in health and in several diseases. We aimed to assess IP in the whole gastrointestinal tract according to body mass index (BMI) and liver steatosis. In 120 patients (61F:59M; mean age 45 ± SEM 1.2 years, range: 18-75), IP was distinctively studied by urine recovery of orally administered sucrose (SO, stomach), lactulose/mannitol ratio (LA/MA, small intestine), and sucralose (SA, colon). By triple quadrupole mass-spectrometry and high-performance liquid chromatography, we measured urinary recovery of saccharide probes. Subjects were stratified according to BMI as normal weight, overweight, and obesity, and answered questionnaires regarding dietary habits and adherence to the Mediterranean Diet. Liver steatosis was assessed by ultrasonography. IP at every gastrointestinal tract was similar in both sexes and decreased with age. Stomach and small intestinal permeability did not differ according to BMI. Colonic permeability increased with BMI, waist, neck, and hip circumferences and was significantly higher in obese than in lean subjects. As determined by logistic regression, the odds ratio (OR) of BMI increment was significantly higher in subjects in the highest tertile of sucralose excretion, also after adjusting for age and consumption of junk food. The presence of liver steatosis was associated with increased colonic permeability. Patients with lower score of adherence to Mediterranean diet had a higher score of 'junk food'. Intestinal permeability tended to increase in subjects with a lower adherence to Mediterranean diet. In conclusion, colonic (but not stomach and small intestinal) permeability seems to be linked to obesity and liver steatosis independently from dietary habits, age, and physical activity. The exact role of these last factors, however, requires specific studies focusing on intestinal permeability. Results should pave the way to both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.
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Role of Calcium and Low-Fat Dairy Foods in Weight-Loss Outcomes Revisited: Results from the Randomized Trial of Effects on Bone and Body Composition in Overweight/Obese Postmenopausal Women.
Ilich, JZ, Kelly, OJ, Liu, PY, Shin, H, Kim, Y, Chi, Y, Wickrama, KKAS, Colic-Baric, I
Nutrients. 2019;11(5)
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A woman’s menopausal years are believed to bring about weight gain due to various biological mechanisms, such as depletion of oestrogen. Many women undertake weight loss diets, in an attempt to control the weight gain, and although weight loss can reduce the risk factors for metabolic and cardiovascular disease etc, it can also lead to accelerated loss bone density and muscle mass. The objective of this study was to investigate whether by complementing a low-calorie diet with 4 to 5 servings of low-fat dairy foods per day and/or supplementing with calcium and vitamin D supplements would aid weight loss and preserve either/both bone and muscle mass. The study was conducted on 189 early postmenopausal, obese women. It was a randomized, placebo-controlled clinical trial conducted over 6 months. Researchers found that results were better for the participants on the low-fat dairy foods and those supplementing with calcium and vitamin D when compared to the placebo group (who only had placebo pills). They suggest that when embarking on a weight loss program it is beneficial to include 4 to 5 servings of low-fat dairy foods each day and take calcium and vitamin D supplements will have a positive impact on weight loss, bone density and muscle mass in post-menopausal women.
Abstract
Several studies have investigated the possibility of dairy foods and calcium (Ca) mediating weight and body composition, but a consensus has not been reached. We aimed to investigate weight-loss-related outcomes during intervention with low-fat dairy foods or Ca + vitamin D supplements, both as complements to hypocaloric diets. Overweight/obese Caucasian, early-postmenopausal women (n = 135) were recruited for a 6 month energy-restricted weight loss study complemented with either low-fat dairy foods (D; 4-5 servings/day), or Ca + vitamin D supplements (S); both to amount a total of ~1500 mg/day and 600 IU/day of Ca and vitamin D, respectively, or placebo pills (C). Bone mineral density (BMD) and lean and fat tissue were measured by Lunar iDXA. Serum and urinary markers of bone turnover were analyzed. Diet and physical activity were assessed with 3-day records. Participants on average lost ~4%, ~3%, and ~2% of body weight, fat, and lean tissue, respectively. The significantly better outcomes were noticed in participants in the D group regarding body composition (fat loss/lean tissue preservation) and in participants in the S group regarding the BMD outcomes, compared to those in the C group. Therefore, increasing low-fat dairy foods to 4-5 servings/day and/or increasing Ca & vitamin D intake by supplements (in those who are at the borderline dietary intake) may be beneficial for weight loss/maintenance and may lead to more favorable bone and body composition outcomes in postmenopausal women during moderate weight loss.
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Cardiovascular Biomarkers in Association with Dietary Intake in a Longitudinal Study of Youth with Type 1 Diabetes.
Sanjeevi, N, Lipsky, LM, Nansel, TR
Nutrients. 2018;10(10)
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Cardiovascular disease (CVD) is the major cause of mortality and morbidity in patients with type 1 diabetes, whose risk is several-fold higher than the general population. The objective of this study was to investigate relationships of CVD biomarkers with overall diet quality, and its dietary components in youth with type 1 diabetes. This study is a secondary analysis of a randomised controlled trial of a family-based behavioural nutrition intervention. The control group had an equal frequency of contact with the research staff but did not receive any nutrition advice besides that included as part of regular type 1 diabetes care. Results indicate that greater intake of whole grains and whole fruits, and lower added sugar and polyunsaturated fatty acids were associated with more favourable CVD biomarkers. Authors conclude that overall diet quality was not associated with CVD biomarkers in youth with type 1 diabetes. However, specific dietary components were associated with CVD biomarkers, independent of glycaemic control.
Abstract
Despite cardioprotective effects of a healthy diet in the general population, few studies have investigated this relationship in individuals with type 1 diabetes, who are at elevated risks of cardiovascular disease (CVD) due to hyperglycemia. The objective of this study was to examine the association of CVD biomarkers with overall diet quality, as measured by the Healthy Eating Index-2015 (HEI-2015), and its dietary components in youth with type 1 diabetes. Youth with type 1 diabetes (n = 136, 8⁻16.9 years) were enrolled in an 18-month behavioral nutrition intervention trial. Dietary intake from three-day diet records, CVD biomarkers (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C); triglycerides (TG), C-reactive protein (CRP), 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), systolic and diastolic blood pressure (SBP and DBP, respectively), and glycated hemoglobin (HbA1c) were assessed at baseline, 6, 12 and 18 months. Linear mixed-effects models estimated associations of dietary intake with CVD biomarkers, adjusting for HbA1c and other covariates. Separate models estimated associations of time-varying change in dietary intake with time-varying change in CVD biomarkers. HEI-2015 was not associated with CVD biomarkers, but whole grain intake was inversely associated with TC, HDL-C and DBP, and a greater increase in whole fruit intake was associated with lower DBP. Added sugar, saturated fat and polyunsaturated fat were positively related to serum TG, HDL-C, and DBP, respectively. Findings suggest that the intake of specific dietary components, including whole grains, whole fruits, added sugar and PUFA, may influence cardiometabolic health in youth with type 1 diabetes, independent of glycemic control.
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A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
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Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
BACKGROUND Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
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Untargeted metabolomic on urine samples after α-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women.
Romo-Hualde, A, Huerta, AE, González-Navarro, CJ, Ramos-López, O, Moreno-Aliaga, MJ, Martínez, JA
Lipids in health and disease. 2018;17(1):103
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Eicosapentaenoic acid (EPA - an omega-3 fatty acid) and alpha-lipoic acid (an antioxidant) have both been investigated for their beneficial impacts on weight loss and heart health. The aim of this double-blind randomised placebo-controlled intervention lasting 8 weeks was to assess the effect of dietary supplementation with EPA and alpha-lipoic acid, separately or in combination, and together with a calorie restricted diet, on breakdown products (metabolites) present in the urine. The study recruited a group of 70 healthy overweight/obese sedentary females. Results indicate a higher reduction in body mass index and fat mass in those groups supplemented with alpha-lipoic acid. EPA supplementation had no effect on urinary breakdown products. Authors conclude that alpha-lipoic acid administration has beneficial effects on body weight reduction, mainly through its antioxidant properties.
Abstract
BACKGROUND Eicosapentaenoic acid (EPA) and α-lipoic acid (α-LA) have been investigated for their beneficial effects on obesity and cardiovascular risk factors. In the current research, the goal was to evaluate metabolomic changes following the dietary supplementation of these two lipids, alone or combined in healthy overweight/obese sedentary women following an energy-restricted diet. For this purpose, an untargeted metabolomics approach was conducted on urine samples using liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOF-MS). METHODS This is a short-term double blind placebo-controlled study with a parallel nutritional design that lasted 10 weeks. Participants were assigned to one of the 4 experimental groups [Control, EPA (1.3 g/d), α-LA (0.3 g/d) and EPA+α-LA (1.3 g/d + 0.3 g/d)]. All intervention groups followed an energy-restricted diet of 30% less than total energy expenditure. Clinically relevant biochemical measurements were analyzed. Urine samples (24 h) were collected at baseline and after 10 weeks. Untargeted metabolomic analysis on urine samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification. RESULTS Urine samples were scattered in the PCA scores plots in response to the supplementation with α-LA. Totally, 28 putative discriminant metabolites in positive ionization, and 6 in negative ionization were identified among groups clearly differentiated according to the α-LA administration. Remarkably is the presence of an ascorbate intermediate metabolite (one of the isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate) in the groups supplemented with α-LA. This fact might be associated with antioxidant properties of both α-LA and ascorbic acid. Correlations between phenotypical parameters and putative metabolites of provided additional information on whether there is a direct or inverse relationship between them. Especially interesting are the negative correlation between ascorbate intermediate metabolite and asymmetric dimethylarginine (ADMA) and the positive one between superoxide dismutase (SOD) and α-LA supplementation. CONCLUSIONS This metabolomic approach supports that the beneficial effects of α-LA administration on body weight reduction may be partly explained by the antioxidant properties of this organosulfur carboxylic acid mediated by isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate. TRIAL REGISTRATION Clinicaltrials.gov NCT01138774 .