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Enhancing Night and Day Circadian Contrast through Sleep Education in Prediabetes and Type 2 Diabetes Mellitus: A Randomized Controlled Trial.
García-Serrano, C, Pujol Salud, J, Aran-Solé, L, Sol, J, Ortiz-Congost, S, Artigues-Barberà, E, Ortega-Bravo, M
Biology. 2022;11(6)
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Diabetes mellitus is a chronic condition that occurs when blood glucose levels increase because the body cannot produce enough insulin or cannot effectively use the insulin it produces. Type 2 diabetes mellitus (T2DM) is the most common type of diabetes. It is a chronic metabolic disease that can be controlled when its pathophysiological factors are neutralised. The aim of this study was to analyse the effect of a sleep hygiene intervention in the management of impaired fasting glucose (IFG) and T2DM. This is an experimental study based on a parallel clinical trial using blocked randomization with equal allocation ratio. A total of 69 participants were included in the analysis (31 and 38 from the control and intervention groups, respectively). Results show a significant improvement in all the measured sleep parameters (sleep quality, time and efficiency). Furthermore, it also demonstrates that sleep health educational intervention, delivered during the regular check-ups of patients with T2DM or IFG, has a positive metabolic effect and is feasible as a complementary therapy in primary care settings. Authors conclude that sleep education improves T2DM metabolic management.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Sleep has a restorative function that benefits glucose metabolism.
- Sleep education should emphasise that maintaining a regular and sufficient sleep schedule and establishing a series of routines and habits in the hours prior to going to sleep would prevent early awakenings.
- Education is an important part of clinical practice.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
The aim of this study was to analyse the effect of a sleep hygiene intervention in the management of impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM).
Methods
This experimental parallel open-label clinical trial included 69 adults with IFG or T2DM.
The intervention was individual informative education which aimed to develop skills to improve sleep, which consisted of:
1. Information: Reading of the educational sheet (9 tips for a healthy sleep) with subsequent discussion.
2. Verification: checking participants understood the advice.
3. Participant information: One telephone call after 1 month was made as educational reinforcement of the intervention.
The controlled group received no educational intervention. The main outcome variable measured was levels of HbA1c (%) 3 and 6 months post intervention. Secondary outcomes were fasting glucose (mg/dL) 3 and 6 months post intervention, Pittsburgh Sleep Quality Index (PSQI), declared sleep hours and sleeping efficiency 3 months post intervention.
Results
- . 84.2% participants from the intervention group and 14.0% in the control group reported a change in sleep habits.
- 3 months after the intervention, the control group did not report any change, while the intervention group reported a statistically significant improvement in all three: PSQI (−2.97 ± 2.93), hours of sleep (1.00 [0.00; 2.00] hours) and sleep efficiency (6.74 ± 12.9%).
- The intervention group achieved a significant reduction in 3 months post intervention fasting glucose levels (−14.69; CI 95%: −28.15, −1.22) and HbA1c levels (−0.39; 95% CI: −0.73, −0.05), as well as a reduction in 6 months post intervention HbA1c levels (−0.66; 95% CI: −0.96, −0.36).
Conclusion
- The results show a significant improvement in all the measured sleep parameters (sleep quality, time and efficiency).
- The PSQI score improvement in the intervention group was 3.6 points higher than the control group.
- The median sleep time in the intervention group was increased by 1.5 h, doubling the number of participants who reported sleeping more than 6 h.
Clinical practice applications:
- An educational intervention in sleep hygiene and circadian contrast may help to increase sleep quality, time and efficiency.
- The educational intervention helped lower HbA1c levels in patients with IFG and T2DM.
- Sleep education helps to improve T2DM metabolic management.
- The 9 tips for a healthy sleep, were developed from the latest guidelines from the American Academy of Sleep Medicine, the National Health Service, and the Health Department of Catalonia.
Considerations for future research:
- The open-labelled intervention and the use of subjective variables related to sleep quality could lead to biassed self-reports in the intervention group so further studies are required.
- Future studies should gather baseline parameters closer to the start of the intervention rather than wait 3 months to assess the immediate outcomes of the intervention.
- Future research could take the same approach with diet and exercise education.
Abstract
BACKGROUND Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. METHODS To determine the effect of an educational intervention delivered by primary care nurses to improve sleep hygiene, a parallel, open-label clinical trial in subjects aged 18 and older with impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) was performed. Study variables were sex, age, fasting glucose, glycated haemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, body mass index, antidiabetic treatment, diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. The intervention aimed to develop skills to improve sleep through nine simple tips. An analysis of covariance was performed on all the mean centred outcome variables controlling for the respective baseline scores. RESULTS In the intervention group, PSQI dropped, the duration and quality of sleep increased, and a decrease in fasting glucose and in HbA1c levels was observed. CONCLUSION The proposed intervention is effective for improving sleep quality, length and efficiency, and for decreasing fasting glucose and HbA1c levels in only 3 months. These findings support the importance of sleep and circadian rhythm education focused on improving IFG and T2DM.
2.
Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.
Singh, A, D'Amico, D, Andreux, PA, Fouassier, AM, Blanco-Bose, W, Evans, M, Aebischer, P, Auwerx, J, Rinsch, C
Cell reports. Medicine. 2022;3(5):100633
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A gradual decline in muscle mass and strength with aging is natural, however, environmental factors such as diet and exercise dictate the trajectory of the decline. Exercise and healthy nutrition are the primary interventions to prevent and manage age-associated decline in muscle health and metabolic diseases. This study was designed as a proof-of-concept investigation of the efficacy of long-term oral supplementation with urolithin A (UA) on physiological endpoints in middle-aged adults. This study is a randomised, double-blind, placebo-controlled study. An overweight middle-aged population with a high body mass index and average physical endurance was selected for the study. Results showed improved lower-body muscle strength in the hamstring skeletal muscle at both doses of UA. Furthermore, it positively impacted aerobic endurance and physical-performance measures such as walking distance. Authors conclude that supplementation with UA is safe and increases circulating levels of UA.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Mitochondrial dysfunction is associated with ageing and linked to deterioration of skeletal muscle and sarcopenia. Improving mitochondrial health may therefore help to improve muscle health as we age.
- Previous studies have demonstrated improvements in muscle endurance with long term UA intake in older adults (1) and the study by Singh et al. supports these findings in middle-aged adults.
- For middle-aged clients who are noticing a decline in muscle strength, exercise performance, or a general increase in fatigue, taking 500-1,000 mg UA daily for two to four months could lead to noticeable improvements in symptoms.
- The compounds from which UA is derived are also found in polyphenol-rich plant foods including pomegranates, berries and walnuts, therefore consuming these foods may be useful dietary additions for the same purpose.
- These findings are likely to be relevant for younger populations too, as mitophagy, which is part of the action of UA, contributes to the removal and recycling of dysfunctional mitochondria, allowing healthier intact mitochondria to take their place.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- Urolithin A (UA) is a microbiome metabolite – known as a postbiotic - of elligitannins and polyphenolic compounds found in some plant foods including pomegratate, berries and walnuts.
- In animal models, UA has previously been shown to have a range of potential health benefits involving induction of mitophagy and on mitochondrial function, as well as on disease states including osteoarthritis, inflammatory bowel disease, cardiovascular disease, and neurodegenerative disorders.
- The current study sought to establish proof-of-concept of the efficacy and safety of long-term UA supplementation on physiological endpoints in middle-aged adults.
- The primary outcome was peak power output and secondary outcomes included a range of clinical and physiological parameters linked to muscle strength, exercise tolerance and physical performance.
- The study tested UA in 500mg and 1000 mg doses against placebo in a 3-arm randomized-controlled trial in n= 88 subjects aged 40-64y who were healthy, overweight (BMI 25.0-34.9 kg/m2), sedentary, and who had a low VO2max at study inclusion. 79 subjects completed the study.
- Subjects were assessed at baseline, midpoint (2 months) and endpoint (4 months). In addition to the UA intervention, subjects were asked to maintain low physical activity status for the duration of the trial, and avoid pomegranates and supplements known to influence muscle performance (high protein, CoQ10m vitamin B3 or L-carnitine).
- Though a difference in peak power output (primary outcome) was not observed, muscle strength improved by up to c. 12% with 500 mg daily UA (p=0.027). With 1000 mg UA daily, aerobic endurance improved by up to 15% (p=0.03), gait speed increased by 7% (p=0.004), and in the 6-minute walk test subjects improved by 7% (p=0.008) and walked on average more than 30 additional meters, indicating a clinically meaningful difference in mobility.
- In addition, subjects in the UA groups had improved biomarkers of cellular health. With 1000 mg UA daily, inflammation was reduced (CRP, p<0.05; IFN-γ and TNF-α, both p<0.05). In addition, biomarkers of mitochondrial efficiency were also improved with 500 mg UA daily, Iing increased protein levels related to improved mitophagy, and expression of genes belonging to mitochondria.
- UA was deemed as safe and well tolerated at both 500 mg and 1000 mg doses for 4 months’ administration.
- A strength of the study was that the groups were balanced for all physiological parameters at baseline. However, the ratio of females was 2:1, and ethnicity was mainly western European. This may limit interpretation of the findings.
- All authors except one are either employees, board members or members of the scientific advisory board of Amazentis SA, who both manufacture Mitopure, the UA supplement used, and who funded this trial.
Clinical practice applications:
- Mitophagy is an important step in improving mitochondrial health. This study demonstrates the potential of UA to activate this pathway.
- In healthy middle-aged adults who are overweight or obese, sedentary and with low physical performance, oral UA supplementation at a sufficient dose and duration may:
- increase muscle strength
- increase mitophagy proteins in human skeletal muscle, as well as various other mitochondrial markers
- increase exercise performance and aerobic exercise
- be a valuable intervention to consider in clients who are suffering from mitochondrial dysfunction
Considerations for future research:
- This study was exploratory and the sample size for some of the outcomes was very small and inadequate to demonstrate true statistical significance. Future studies of similar design are needed to confirm the findings
- Nevertheless, the study was well-structured with carefully elaborated markers. It could be used as a template for future studies.
Abstract
Targeting mitophagy to activate the recycling of faulty mitochondria during aging is a strategy to mitigate muscle decline. We present results from a randomized, placebo-controlled trial in middle-aged adults where we administer a postbiotic compound Urolithin A (Mitopure), a known mitophagy activator, at two doses for 4 months (NCT03464500). The data show significant improvements in muscle strength (∼12%) with intake of Urolithin A. We observe clinically meaningful improvements with Urolithin A on aerobic endurance (peak oxygen oxygen consumption [VO2]) and physical performance (6 min walk test) but do not notice a significant improvement on peak power output (primary endpoint). Levels of plasma acylcarnitines and C-reactive proteins are significantly lower with Urolithin A, indicating higher mitochondrial efficiency and reduced inflammation. We also examine expression of proteins linked to mitophagy and mitochondrial metabolism in skeletal muscle and find a significant increase with Urolithin A administration. This study highlights the benefit of Urolithin A to improve muscle performance.
3.
Effect of sleep duration on dietary intake, desire to eat, measures of food intake and metabolic hormones: A systematic review of clinical trials.
Soltanieh, S, Solgi, S, Ansari, M, Santos, HO, Abbasi, B
Clinical nutrition ESPEN. 2021;45:55-65
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Adequate sleep is crucial to health. Yet, sleep disturbances have become very common in modern societies. A lack of sleep is linked to increased risk for several chronic diseases such as diabetes, high blood pressure, metabolic syndrome and cardiovascular disease. Furthermore, appetite-regulating hormones can be disrupted by sleep shortages, which is thought to drive chronic overeating, leading to weight gain, obesity and its associated health consequences. This review examined the relationship between sleep duration and food consumption and energy intake, whilst also monitoring changes in body weight and appetite-regulating hormones. The review encompassed 50 randomized controlled trials (RCTs) with 3387 participants, including 1079 children and adolescents and 2308 adults. The findings suggested that sleep shortages contribute to significant increases in calorie intake, fat intake, increased body weight, appetite, hunger, more frequent eating and bigger portion sizes. In this review lack of sleep did not change protein and carbohydrate intake. Nor did lack of sleep make people exert more or less energy overall, however, a variance amongst ethnic groups was observed here. There was not enough evidence for changes in metabolic rate, so the review assumed no significant effect. When viewed collectively, the appetite-regulating hormones of leptin and ghrelin, the stress hormone cortisol and the sugar-regulating hormone insulin were not significantly influenced by sleep duration. However, there seemed to be a wide variance of outcomes when looking at individual studies' results. In conclusion, the authors reiterated the importance of sleep for health maintenance, advocating for a minimum of 7 hours of sleep per day for adults and that, despite busy modern lifestyles, sleep optimisation strategies should be prioritised. Less than 6 hours of sleep per day increases the risk of health consequences, like weight gain and metabolic disorders and sleep management should be considered part of their treatment protocols.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Reduced sleep duration may serve as a mediator for weight gain in part due to increased appetite, increased fat intake and disruptions to energy balance.
- Enhancing sleep quality may serve to support weight loss protocols.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Short sleep duration and disruptions to circadian rhythm have been associated with being overweight and obese. It has been suggested that sleep restriction may interfere with appetite regulating hormones leading to increased appetite and disrupted energy balance.
This study aimed to systematically review studies exploring the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics and appetite-regulating hormones.
Methods
This systematic review included 50 randomised controlled trials including 3,387 participants.
Results
Energy intake
- 13 out of 30 the included studies found that short sleep conditions led to higher energy intake.
- 1 study identified that sleep restriction resulted in a 15.3% and 9.2% increase in energy intake in both women and men.
- 3 studies noted that prolonging sleep duration led to a reduction in energy intake.
- 1 study reported a reduction in energy intake after sleep restriction (P=0.031).
Fat consumption
- 9 studies out of 22 identified a significant association between short sleep and increased fat consumption.
- 7 studies did not identify a difference between groups.
- 3 studies noted a decrease in fat consumption following prolonged sleep (P<0.001, P<0.05, P=0.04).
Hunger and appetite
- 11 studies out of 17 observed that sleep restriction resulted in increased hunger ratings.
- 3 studies found an increase in appetite following sleep restriction (P<0.01) with 3 finding no difference..
- 1 study reported a decrease in appetite following sleep restriction.
- 2 studies noted that portion sizes increased as a result of sleep restriction (P<0.01).
- 1 study reported an increase in eating occasions following restricted sleep compared to habitual sleep (6.08 vs 4.96).
Body weight
- 6 studies out of 14 found no effect of sleep loss on body weight.
- 4 studies identified that sleep restriction led to weight gain (P<0.001, P<0.05, P=0.14, P=0.031).
- 2 studies reported weight loss following increased sleep duration (P<0.001).
Ghrelin and leptin
- Leptin and ghrelin levels were generally not found to be influenced by sleep duration, with the exception of a few studies.
Clinical practice applications:
Reduced sleep duration may promote weight gain by:
- Increasing energy intake.
- Increasing fat consumption.
- Increasing hunger and appetite.
- Increasing portion sizes and eating occasions.
Prolonging sleep duration may support weight loss by:
- Reducing energy intake.
- Reducing fat intake.
Considerations for future research:
- Mixed results on the influence of sleep restriction on appetite regulating hormones, leptin and ghrelin.
- Some studies noted the negative impact of sleep restriction on leptin and ghrelin concentrations, collectively shortened sleep duration did not appear to influence these hormones.
- Further sleep restriction studies exploring additional appetite regulating hormones and neuropeptides and the reward system may provide a more definitive understanding of the underlying mechanism for reduced sleep duration to disrupt the appetite and energy balance and promote weight gain.
Abstract
BACKGROUND AND AIMS Sleep, as well as diet and physical activity, plays a significant role in growth, maturation, health, and regulation of energy homeostasis. Recently, there is increasing evidence indicating a possible causal association between sleep duration and energy balance. We aimed to examine the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics, and appetite-regulating hormones by randomized controlled trials (RCTs). METHODS Electronic literature searches were conducted on Medline, Web of Science, and Google Scholar until July 2020. The search was conducted with the following words: "Sleep Duration", "Circadian Rhythm", "Sleep Disorders" in combination with "Obesity", "Overweight", "Abdominal Obesity", "Physical Activity", "Energy Intake", "Body Mass Index", "Lipid Metabolism", "Caloric Restriction", Leptin, "Weight Gain", and "Appetite Regulation" using human studies.methods RESULTS After screening 708 abstracts, 50 RCTs (7 on children or adolescents and 43 on adults) were identified and met the inclusion criteria. In general, the findings suggested that sleep restriction may leads to a significant increment in energy intake, fat intake, body weight, appetite, hunger, eating occasions, and portion size, while protein and carbohydrate consumption, total energy expenditure, and respiratory quotient remained unaffected as a result of sleep restriction. Serum leptin, ghrelin, and cortisol concentrations were not influenced by sleep duration as well. CONCLUSION Insufficient sleep can be considered as a contributing factor for energy imbalance, weight gain, and metabolic disorders and it is suggested that to tackle disordered eating it may be necessary to pay more attention to sleep duration.
4.
Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial.
Most, J, Timmers, S, Warnke, I, Jocken, JW, van Boekschoten, M, de Groot, P, Bendik, I, Schrauwen, P, Goossens, GH, Blaak, EE
The American journal of clinical nutrition. 2016;104(1):215-27
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The prevalence of obesity and related chronic diseases is continuously increasing. Insulin resistance is a major risk factor for the progression of obesity toward chronic metabolic diseases, including cardiovascular disease and type 2 diabetes. Polyphenols were identified as dietary ingredients with antioxidant properties decades ago. Epigallocatechin-3-gallate (EGCG), which is most abundant in green tea, and resveratrol (RS), which is present in grape skins, have been implicated in the prevention of body weight gain and improvements in markers of insulin sensitivity in human and animal studies. The aim of this randomised control study was to investigate the longer-term effect of EGCG and RES (EGCG+RES) supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue-specific insulin sensitivity. 38 overweight and obese men and women received supplementation with either EGCG+RES (282 and 80 mg/d, respectively) or a placebo for 12 weeks. Before and after the intervention, oxidative capacity, lipid metabolism and insulin sensitivity were measured. EGCG+RES supplementation did not affect the fasting plasma metabolic profile. Although whole-body fat mass was not affected, visceral adipose tissue mass decreased after the intervention compared with placebo. EGCG+RES supplementation significantly increased oxidative capacity in muscle fibres. Fat oxidation and energy expenditure were not significantly affected by EGCG+RES. Finally, EGCG+RES had no effect on insulin-stimulated glucose disposal, suppression of endogenous glucose production, or lipolysis. The authors concluded that 12 weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo, and this may improve physical condition and play a role in the prevention of weight gain and worsening of insulin resistance in the long term.
Expert Review
Conflicts of interest:
None
Take Home Message:
- 12 wks of EGCG+RES intake increased skeletal muscle oxidative capacity as well as upregulating mitochondrial pathways, which may translate into an improved metabolic risk profile over time because greater mitochondrial capacity has been associated with higher insulin sensitivity in other studies
- The fat oxidation alterations in those taking the active ingredients vs. the placebo group suggests that this intervention could lead to metabolic adaptation towards lipids instead of CHOs as a fuel source, over time.
- EGCG+RES intake attenuated the increase in plasma triacylglycerol levels during the HFMM test, while the levels were significantly increased in the placebo group after 12 wks. This suggests that the intervention may provide positive support for individuals with high triacylglcerol (triglyceride) levels
- The ratio of total cholesterol to HDL cholesterol tended to decrease after EGCG+RES supplementation but not after placebo. Increased total & HDL cholesterol marker for myocardial infarction risk, so this intervention could help with persons who have disordered cholesterol values, and perhaps contribute to reducing their MI risk over time.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- This randomised controlled trial investigated the effect of 12-wk supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and insulin sensitivity.
- 38 overweight and obese subjects (active ingredient cohort n = 18; placebo n = 20) received 282 mg/d EGCG and 80 mg/d resveratrol; one capsule of each was taken at breakfast and dinner. Subjects were medically screened 10 times in total, including: 3 times before starting supplementation, 3 times during the supplementation period, and 3 in the last week of supplementation.
- EGCG capsules contained 94% epigallocatechin-3-gallate (141 mg/capsule) and resveratrol capsules contained 20% trans-resveratrol (40 mg trans-resveratrol in Polygonum cuspidatum extract/capsule).
- Medical screening included skeletal muscle biopsies (Vastus lateralis), with various tests done to measure oxidative capacity, X-ray absorptionmetry, a high-fat mixed meal (HFMM) test, and an insulin test via hyperinsulinemic-euglycemic clamp; meal intake before screening was standardised.
- Blood probes were also taken, and subjects completed food records; exact kcals per macronutrient were calculated.
Clinical practice applications:
The results of the study, which relate to clinical practice, highlight:
- 12 weeks of ECGC+RES supplementation increased mitochondrial capacity.
- EGCG+RES increased skeletal muscle oxidative capacity as well as protein expression of OxPhos complexes in skeletal muscle.
- EGCG+RES supplementation significantly affected fasting substrate oxidation, whereas fat oxidation declined in the placebo group; this suggests that it could help to improve fat metabolism.
- 12 weeks of ECGC+RES supplementation preserved fasting and postprandial fat oxidation compared with placebo.
- Plasma triacylglycerol levels were not significantly increased in the EGCG+RES cohort on being given an HFMM test after 12 wks, whereas they went up in the placebo group, indicating that this intervention preserved fasting and post-prandial fat oxidation.
- EGCG+RES group tended to decrease visceral adipose tissue mass by ~11% vs. placebo,
- These findings suggest that combined ECGC+RES supplementation might support mitochondrial function and weight loss/insulin sensitivity over a longer period of time
Considerations for future research:
- The EGCG+RES supplementation had no effect on postprandial glucose, insulin and FFA concentrations or local interstitial glucose and glycerol concentrations. Altering the study parameters in the future might identify changes of these markers.
- There was a tendency toward visceral adipose tissue mass decrease that was not considered significant, but altering dosage and length of time of a similar study might result in a more notable outcome related to weight loss, which was a targeted endpoint
- The combined supplements were not found to affect energy expenditure, contrary to a previous study by the same team, which was for a much shorter time period. It would be interesting to identify why this was.
- Complex and numerous gene set enrichment analyses were performed indicating that the most upregulated pathways after EGCG+RES supplementation were related to the Krebs cycle and electron transport chain, whereas pathways related to CHO metabolism were upregulated in the placebo group. This was taken to indicate that the increased mitochondrial capacity after EGCG +RES supplementation is accompanied by changes at the transcriptional and translational levels; further follow-up of this would be useful to know what clinical impact this has longer term
Abstract
BACKGROUND The obese insulin-resistant state is characterized by impairments in lipid metabolism. We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal (HFMM) test in men. OBJECTIVE The present study aimed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue-specific insulin sensitivity. DESIGN In this randomized double-blind study, 38 overweight and obese subjects [18 men; aged 38 ± 2 y; body mass index (kg/m(2)): 29.7 ± 0.5] received either EGCG+RES (282 and 80 mg/d, respectively) or placebo for 12 wk. Before and after the intervention, oxidative capacity and gene expression were assessed in skeletal muscle. Fasting and postprandial (HFMM) lipid metabolism was assessed by using indirect calorimetry, blood sampling, and microdialysis. Tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with [6,6-(2)H2]-glucose infusion. RESULTS EGCG+RES supplementation did not affect the fasting plasma metabolic profile. Although whole-body fat mass was not affected, visceral adipose tissue mass tended to decrease after the intervention compared with placebo (P-time × treatment = 0.09). EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers (P-time × treatment < 0.05, P-EGCG+RES < 0.05). Moreover, EGCG+RES reduced fasting (P-time × treatment = 0.03) and postprandial respiratory quotient (P-time × treatment = 0.01) compared with placebo. Fasting and postprandial fat oxidation was not significantly affected by EGCG+RES (P-EGCG+RES = 0.46 and 0.38, respectively) but declined after placebo (P-placebo = 0.05 and 0.03, respectively). Energy expenditure was not altered (P-time × treatment = 0.96). Furthermore, EGCG+RES supplementation attenuated the increase in plasma triacylglycerol concentrations during the HFMM test that was observed after placebo (P-time × treatment = 0.04, P-placebo = 0.01). Finally, EGCG+RES had no effect on insulin-stimulated glucose disposal, suppression of endogenous glucose production, or lipolysis. CONCLUSION Twelve weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects. This trial was registered at clinicaltrials.gov as NCT02381145.