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Effect of a Protein Supplement on the Gut Microbiota of Endurance Athletes: A Randomized, Controlled, Double-Blind Pilot Study.
Moreno-Pérez, D, Bressa, C, Bailén, M, Hamed-Bousdar, S, Naclerio, F, Carmona, M, Pérez, M, González-Soltero, R, Montalvo-Lominchar, MG, Carabaña, C, et al
Nutrients. 2018;10(3)
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Protein supplements are popular among athletes to improve performance and increase muscle mass. However, their effect on other aspects of health is less well known. Dietary changes can affect gut microbiota balance, with beneficial or harmful consequences for the host. This small pilot study was performed on cross-country runners whose diets were complemented with a protein supplement (whey isolate and beef hydrolysate) or maltodextrin (control) for 10 weeks. Microbiota, water content, pH, ammonia, and short-chain fatty acids (SCFAs) were analysed in faecal samples, and oxidative stress markers were measured in blood plasma and urine. Faecal pH, water content, ammonia, and SCFA concentrations did not change, indicating that protein supplementation did not increase the presence of these metabolites of fermentation. Similarly, it had no impact on plasma or urine malondialdehyde levels. Protein supplementation did however increase the abundance of the Bacteroidetes phylum and decrease the presence of health-related taxa including Roseburia, Blautia, and Bifidobacterium longum. The authors concluded that long-term protein supplementation may have a negative impact on gut microbiota. Further research is needed to establish the impact of protein supplements on gut microbiota.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Long-term protein supplementation may have a negative impact on gut microbiota.
- Further research is needed to establish the impact of protein supplements on gut microbiota and whether there is a differential impact between protein from animal and plant sources.
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 is a very interesting study that is relevant to athletic populations.
Clinical practice applications:
Potentially there is a role for probiotics / prebiotics when increasing protein intake (particularly of animal origin) to maintain microbiota diversity and prevent ensuing health complications.
Considerations for future research:
Further, larger scale, research is needed to understand whether the same effect of protein supplementation would be seen with plant-based proteins or whether this is unique to animal based protein supplementation. For example, is the hydrolysation of the proteins to account for the largest effect or could a whole food protein, i.e. not hydrolysed, elicit the same effects?
Also, is this effect seen in other sports, e.g. non-endurance. What about the effect under different conditions e.g. energy deficit vs. energy excess?
Abstract
Nutritional supplements are popular among athletes to improve performance and physical recovery. Protein supplements fulfill this function by improving performance and increasing muscle mass; however, their effect on other organs or systems is less well known. Diet alterations can induce gut microbiota imbalance, with beneficial or deleterious consequences for the host. To test this, we performed a randomized pilot study in cross-country runners whose diets were complemented with a protein supplement (whey isolate and beef hydrolysate) (n = 12) or maltodextrin (control) (n = 12) for 10 weeks. Microbiota, water content, pH, ammonia, and short-chain fatty acids (SCFAs) were analyzed in fecal samples, whereas malondialdehyde levels (oxidative stress marker) were determined in plasma and urine. Fecal pH, water content, ammonia, and SCFA concentrations did not change, indicating that protein supplementation did not increase the presence of these fermentation-derived metabolites. Similarly, it had no impact on plasma or urine malondialdehyde levels; however, it increased the abundance of the Bacteroidetes phylum and decreased the presence of health-related taxa including Roseburia, Blautia, and Bifidobacterium longum. Thus, long-term protein supplementation may have a negative impact on gut microbiota. Further research is needed to establish the impact of protein supplements on gut microbiota.
2.
Type-4 Resistant Starch in Substitution for Available Carbohydrate Reduces Postprandial Glycemic Response and Hunger in Acute, Randomized, Double-Blind, Controlled Study.
Stewart, ML, Wilcox, ML, Bell, M, Buggia, MA, Maki, KC
Nutrients. 2018;10(2)
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Resistant starch is a combination of dietary fibre and carbohydrate that ‘resists’ digestion in the small intestine and is fermented in the large intestine by gut bacteria. It is associated with a number of health benefits, particularly the management of blood glucose levels. This small double-blind, randomised controlled trail allocated 36 healthy individuals (mostly female, average age 46 and BMI 26) to eat either a low-fibre scone or a scone with added resistant starch in the form of acid-hydrolyzed and heat treated maize starch. The response of blood glucose and blood insulin levels were measured, as well as participants feeling of fullness and intestinal comfort after eating the scones. The scone with the added resistant starch had significantly lower blood glucose (43-45% lower) and blood insulin (35-40% lower) levels after eating the scone, when compared to those eating the low-fibre scone. They also reported feeling fuller for longer and had no particular digestive symptoms. Whilst this is a small study, Nutrition Practitioners may want to investigate dietary sources of resistant starch when working with clients to balance blood glucose and insulin levels.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Based on the findings of the Predict Study, it is highly probable that the same meal will elicit a different glycaemic response in individuals with different gut microbial compositions.
- The gut microbiota, therefore, needs to be taken into consideration when assessing glycaemic responses to a meal.
- Healthcare practitioners may like to consider the use of resistant starches as an additional tool to balance blood sugar responses to a meal.
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:
Dietary modulation of the gut microbiota impacts human health. This paper discusses the effects of a man-made type of resistant starch on the glycaemic response to a meal. Based on the initial findings of the Predict Study, it is highly probably that the same meal will elicit a different glycaemic (and wider metabolic) response in individuals with different gut microbial compositions. So this paper confirms the need to take the gut microbiota into consideration when assessing glycaemic responses to a meal, both in research and in clinical practice.
Clinical practice applications:
Not all fibres are equal, and not all starches are equal. Type 4 resistant starch is a novel addition to the already known types 1, 2, and 3 and provides with clinicians with an additional tool to balance their patient's blood sugar response to a meal based on the effect of resistant starch on the gut microbiota.
Considerations for future research:
Resistant starches are known for their ability to affect gut microbiota composition and short-chain fatty acid concentrations which, in turn, have the ability to modulate immune and metabolic functions in the host, including cholesterol, fasting glucose, glycosylated haemoglobin, and pro-inflammatory markers. Further studies on glycaemic and wider metabolic responses to a meal must take into consideration the effect of resistant starches on gut microbial composition. Not doing so may be skewing scientific findings.
Abstract
Resistant starch (RS) is a type of dietary fiber that has been acknowledged for multiple physiological benefits. Resistant starch type 4 (RS4) is a subcategory of RS that has been more intensively studied as new types of RS4 emerge in the food supply. The primary aim of this randomized, double-blind, controlled study was to characterize the postprandial glucose response in healthy adults after consuming a high fiber scone containing a novel RS4 or a low fiber control scone without RS4. Secondary aims included assessment of postprandial insulin response, postprandial satiety, and gastrointestinal tolerance. The fiber scone significantly reduced postprandial glucose and insulin incremental areas under the curves (43-45% reduction, 35-40% reduction, respectively) and postprandial glucose and insulin maximum concentrations (8-10% and 22% reduction, respectively). The fiber scone significantly reduced hunger and desire to eat during the 180 min following consumption and yielded no gastrointestinal side effects compared with the control scone. The results from this study demonstrate that a ready-to-eat baked-good, such as a scone, can be formulated with RS4 replacing refined wheat flour to yield statistically significant and clinically meaningful reductions in blood glucose and insulin excursions. This is the first study to report increased satiety after short-term RS4 intake, which warrants further investigation in long-term feeding studies.
3.
Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial.
Lambert, MNT, Thybo, CB, Lykkeboe, S, Rasmussen, LM, Frette, X, Christensen, LP, Jeppesen, PB
The American journal of clinical nutrition. 2017;106(3):909-920
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Oestrogens play a vital role in maintaining bone health. The natural decline in oestrogen during menopause negatively impacts bone mineral density and increases the risk of osteoporosis and fractures. Standard interventions offered include calcium and vitamin D supplementation and hormone replacement therapy. As hormone replacement therapy is associated with increased cancer risk, there is a need to find effective treatments that display a suitable safety profile for long-term use. Isoflavones are compounds found in legume plants, many of which are dietary staples in some cultures. Isoflavones are phytoestrogens, substances that can selectively interact with human oestrogen receptors. Initial research on Isoflavones indicated that it reduces bone breakdown whilst showing protective effects for certain cancers. This randomized, double- blind, placebo-controlled trial compared the effectiveness of an lactic acid fermented, probiotic-rich isoflavone product from Red Clover (RCE) or a placebo, when given in addition to Calcium, Magnesium and Vitamin D (CMD) in postmenopausal women with osteopenia. Participants were monitored using blood tests assessing phytoestrogen activity and oestrogen metabolism, DXA scans to observe changes in bone structure and activity and dietary questionnaires. A total of 78 participants completed the study. The results showed that twice a day 60 mg isoflavones from RCE had a significant physiological impact on preventing bone loss associated with oestrogen deficiency, and was more effective in preserving bone density than CDM alone. The authors concluded that RCE was close to effectiveness to conventional bone-preserving treatments like hormone therapy but stood out due to its better safety profile and minimal side effects. Gut bacteria enhance the effectiveness of these isoflavones, which can be metabolised into compounds called equol. While before the study none of the participants could produce equol, in the end, half of the participants in the RCE group were able to produce equol, suggesting that the probiotic presence in the supplement positively influenced the participants' gut bacteria, creating favourable conditions. Additionally, RCE treatment led to favourable changes in urinary oestrogen metabolites associated with less carcinogenic oestrogen metabolism. In conclusion, the probiotic RCE, enhanced the effectiveness of CMD in preventing bone loss, whilst also increasing the ability to produce equol.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Fermented red clover extract, rich in bioavailable isoflavones with selective oestrogen receptor affinity and probiotics, combined with traditional supplementation (calcium, magnesium and vitamin D) improves bone mineral density and bone turnover compared to placebo in post menopausal women with osteopenia.
- Combining probiotics with isoflavones appears to enhance intestinal isoflavone uptake and isoflavone metabolism.
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
This was a well-constructed randomised, parallel-design, placebo-controlled, double-blind trial over 12 months. The primary aim was to determine the effectiveness of a novel fermented red clover extract (RCE) containing isoflavones and probiotics combined with traditional calcium/magnesium/vitamin D supplementation, in comparison with traditional calcium/magnesium/vitamin D supplementation alone on bone mineral density (BMD) in postmenopausal women with osteopenia.
Methods
- The trial followed the guidelines of the Declaration of Helsinki and received ethics approval.
- Inclusion criteria: female; >=1 year postmenopause; age 60-85; and bone T score of -1 to -2.25.
- Exclusion criteria: medical treatment for osteopenia or hormone replacement therapy within the past 3 months; diet rich in or supplementation with isoflavones; supplementation with Vitamin K; medical history of stipulated conditions.
- 85 participants were eligible and randomised to either the control or treatment group.
- Treatment group received 95 mL of RCE twice daily, containing 60 mg isoflavone aglycones and probiotics, plus 1040mg calcium, 487mg magnesium and 25μg Vitamin D daily (CMD/d). Control group received masked RCE placebo plus CMD/d.
Results
- The change in BMD (p=0.043) and T score (p=0.045) showed a statistically significant greater decrease in the lumbar spine, femoral neck and hip of the control group than the RCE treatment group after 12 months of treatment.
- A statistically significant reduction in one bone resorption marker was found in the RCE group compared to control (p=0.045). All other bone biomarkers failed to reach significance.
- Plasma isoflavone concentration was elevated in the RCE treatment group compared to control (p=0.0094).
- The concentration ratios of urinary oestrogen metabolites 2-OH:16αOH was significantly increased in the RCE group compared to control (p=0.026).
Conclusion
Fermented RCE with CMD/d slowed oestrogen-deficient BMD loss and improved one marker of bone turnover in postmenopausal osteopenic women. Combining RCE with CMD/d was found to be more effective in preserving bone density than CMD/d alone in this target group. Probiotics in the fermented RCE appear to enhance intestinal isoflavone uptake, metabolism, and therapeutic effect.
Clinical practice applications:
- Healthcare practitioners working with women in post-menopause with osteopenia could consider the addition of fermented RCE with CMD/d for improved bone mineral density and bone turnover over 12 months.
- Given the positive impact of RCE intake over 12 months on 2-OH:16αOH oestrogen metabolite ratios, healthcare practitioners could consider fermented RCE when HRT is not an available option in relation to cancer risk.
- Based on these results, Nutritional Therapists working with post-menopausal women with osteopenia can focus on dietary isoflavone intake and pre and probiotic foods to support BMD, alongside supplementary options.
Considerations for future research:
- Given the length of time taken in bone remodelling cycles, a clinical trial of more than 2 years would strengthen the evidence provided by DXA scan.
- All trial participants were normotensive and healthy weight. Future studies could include women with hypertension and obesity to determine effects of RCE on bone and blood pressure/lipid markers in this group.
- Controlled feeding studies to determine the dietary effects of isoflavones and pre and probiotic foods would provide additional information in this area.
- Other fermented RCE products should be trialled to replicate findings.
Abstract
Background: Female age-related estrogen deficiency increases the risk of osteoporosis, which can be effectively treated with the use of hormone replacement therapy. However, hormone replacement therapy is demonstrated to increase cancer risk. Bioavailable isoflavones with selective estrogen receptor affinity show potential to prevent and treat osteoporosis while minimizing or eliminating carcinogenic side effects.Objective: In this study, we sought to determine the beneficial effects of a bioavailable isoflavone and probiotic treatment against postmenopausal osteopenia.Design: We used a novel red clover extract (RCE) rich in isoflavone aglycones and probiotics to concomitantly promote uptake and a favorable intestinal bacterial profile to enhance isoflavone bioavailability. This was a 12-mo, double-blind, parallel design, placebo-controlled, randomized controlled trial of 78 postmenopausal osteopenic women supplemented with calcium (1200 mg/d), magnesium (550 mg/d), and calcitriol (25 μg/d) given either RCE (60 mg isoflavone aglycones/d and probiotics) or a masked placebo [control (CON)].Results: RCE significantly attenuated bone mineral density (BMD) loss at the L2-L4 lumbar spine vertebra (P < 0.05), femoral neck (P < 0.01), and trochanter (P < 0.01) compared with CON (-0.99% and -2.2%; -1.04% and -3.05%; and -0.67% and -2.79, respectively). Plasma concentrations of collagen type 1 cross-linked C-telopeptide was significantly decreased in the RCE group (P < 0.05) compared with CON (-9.40% and -6.76%, respectively). RCE significantly elevated the plasma isoflavone concentration (P < 0.05), the urinary 2-hydroxyestrone (2-OH) to 16α-hydroxyestrone (16α-OH) ratio (P < 0.05), and equol-producer status (P < 0.05) compared with CON. RCE had no significant effect on other bone turnover biomarkers. Self-reported diet and physical activity were consistent and differences were nonsignificant between groups throughout the study. RCE was well tolerated with no adverse events.Conclusions: Twice daily RCE intake over 1 y potently attenuated BMD loss caused by estrogen deficiency, improved bone turnover, promoted a favorable estrogen metabolite profile (2-OH:16α-OH), and stimulated equol production in postmenopausal women with osteopenia. RCE intake combined with supplementation (calcium, magnesium, and calcitriol) was more effective than supplementation alone. This trial was registered at clinicaltrials.gov as NCT02174666.
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.