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Gut feelings: A randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms.
Chahwan, B, Kwan, S, Isik, A, van Hemert, S, Burke, C, Roberts, L
Journal of affective disorders. 2019;253:317-326
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Depression is a debilitating psychiatric disorder that is the leading cause of disability world-wide. Multiple causes of depression have been identified, including genetic, neurological, inflammatory, personality, cognitive, and environmental factors. The aim of this study was to investigate the effectiveness of the multispecies probiotic Ecologic® Barrier for reducing symptoms in adults with mild to severe levels of depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial. Participants were randomly allocated into two groups; probiotic and placebo. 71 participants with depressive symptoms were recruited and allocated sequentially over 12 months. Results indicate that all participants across both probiotic and placebo groups exhibited a reduction in depressive symptoms over the time-period of the trial. Thus, the routine involved with daily preparation and consumption of the probiotic and scheduled appointments, as well as involvement in these behaviours with the aim of seeking improvement in depressive symptoms had positive impacts on mood, irrespective of whether the probiotic or placebo was consumed. Authors conclude that their findings offer evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
- The study suggests that probiotics, rather than having a direct effect on depressive symptoms, potentially act on immune system activity, inflammation and gut barrier integrity which contribute to the expression of depression.
- Probiotics may be a useful adjunct to potentiate the effects of other therapies, such as CBT.
- This study points to the validity of managing physical health as part of mental health treatment.
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:
With evidence suggesting that decreased gut barrier function and inflammation are correlated with depression, this study set out to determine the effect of consumption of probiotic supplements on depressive symptoms from a sample of 71 participants with depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial conducted over 8 weeks in Australia. Pre and post intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota were compared alongside psychological variables and gut microbiota composition to non-depressed, placebo and probiotic groups. All the clinical trial participants demonstrated an improvement in symptoms – participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group. Probiotics did not significantly alter the microbiota of depressed individuals, however a significant correlation was found between Ruminococcus gnavus and one of the metrics for depression.
Clinical practice applications:
This study was small and carried out over a short period of time. While significant results were found, which signify potential considerations for clinical practice, the results from this study do not offer evidence that the probiotics used had a direct effect on depressive symptoms – they suggest that probiotics potentially act on cognitive processes contributing to depression which may include immune system activity, inflammation, and gut barrier integrity. Overall, this study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression. In clinical practice, probiotics may be a useful adjunct to potentiate the effects of therapies, such as CBT. Finally, the use of probiotics promotes the concept of managing physical health as part of mental health treatment.
Considerations for future research:
These preliminary results are promising and offer a number of future research and clinical avenues to build upon. The results do however, indicate that a longer trial may be needed to fully assess the effects of probiotics on mood and the mechanisms by which probiotics may be influencing this. The study also suggests that further research using a range of concentrations in a dose response study may be warranted to determine the optimal dose; a greater dose over a longer period may produce detectable changes in microbiota as well as further differences in psychological data.
Abstract
BACKGROUND Depression is the leading cause of disability worldwide; with evidence suggesting that decreased gut barrier function and inflammation are correlated with depressive symptoms. We conducted a clinical trial to determine the effect of consumption of probiotic supplements (Winclove's Ecologic® Barrier) on depressive symptoms in a sample of participants with mild to severe depression. METHOD 71 participants were randomly allocated to either probiotic or placebo, which was, consumed daily over eight weeks. Pre- and post-intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota composition were compared. Clinical trial participants were also compared on psychological variables and gut microbiota composition to a non-depressed group (n = 20). RESULTS All clinical trial participants demonstrated improvement in symptoms, suggesting non-specific therapeutic effects associated with weekly monitoring visits. Participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group, particularly in the mild/moderate subgroup. Probiotics did not significantly alter the microbiota of depressed individuals, however, a significant correlation was found between Ruminococcus gnavus and one depression metric. LIMITATIONS There was a high attrition rate, which may be attributed to weekly monitoring visits. Additionally, modulation of the gut microbiota may need more specific testing to distinguish subtle changes. CONCLUSIONS While microbiota composition was similar between all groups, probiotics did affect a psychological variable associated with susceptibility to depression. Further research is needed to investigate how probiotics can be utilised to modify mental wellbeing, and whether they can act as an adjunct to existing treatments.
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Broccoli consumption affects the human gastrointestinal microbiota.
Kaczmarek, JL, Liu, X, Charron, CS, Novotny, JA, Jeffery, EH, Seifried, HE, Ross, SA, Miller, MJ, Swanson, KS, Holscher, HD
The Journal of nutritional biochemistry. 2019;63:27-34
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Diet affects metabolic and gastrointestinal diseases, with the microbiome considered to be a mediating factor. Broccoli is a good source of fibre and phytochemicals including glucosinolates. The aim of this investigator-blinded, controlled feeding, randomised, crossover study was to evaluate the effects of broccoli on the composition and function of the microbiome. 18 healthy adults received 200 g cooked broccoli and 20 g raw daikon radish per day for 18 days in addition to a controlled, brassica-free diet or the same diet without the broccoli and daikon radish, with a 24-day washout period. A statistically significant increase in the ratio of Bacteroidetes to Firmicutes was observed following the broccoli intervention. When stratified by BMI above or below 25, this increase was only seen in those with a lower BMI whilst those with a higher BMI displayed a decrease in the ratio, although the latter was not statistically significant. In those with the lower BMI, there was also a correlation between the changes in the microbiota composition and glucosinolate metabolites. It was predicted that the involved changes would affect the functions of the endocrine system, transport and catabolism and energy metabolism. The authors concluded that eating broccoli may affect both the composition and the function of the microbiome.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Broccoli consumption at dosages of 200g per day were shown to change the composition of gastrointestinal microbiota, increasing Bacteroidetes and decreasing Firmicutes, and impact their function
- The observed results were strongest in those with a BMI of less than 26
- While interesting, the study only included 18 participants and therefore the results should be further confirmed.
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
There is growing evidence linking dysbiosis of the gastrointestinal microbiota and diet-induced gastrointestinal and metabolic diseases. Both long-term and acute dietary changes, fasting, eating frequency, and consumption of specific fibres and food phytochemicals play a role in shaping the composition and function of the microbiota, although evidence is lacking for specific foods. This study aimed to determine the impact of broccoli intake on the number of bacterial strains and their functional capacity.
Methods
This was a single-blind, randomised, crossover, complete feeding intervention. Study participants were healthy adults (n=18, females =10). Participants were requested to not eat Brassica vegetables for 3 weeks before the start of the study.
Subjects participated in two 18-day diet periods separated by a 24-hour washout, during which breakfast and dinner were consumed on site to observe compliance. The control diet was prepared using traditional American foods, excluding all Brassica vegetables. During the broccoli intervention period, participants consumed the same base diet with the addition of 200g of broccoli.
Faecal samples were collected on day 1, and day 16. Quantitative polymerase chain reaction was performed on bacterial strains. On day 17, time series plasma sampling and 24-hour urine collection was done.
Results
There was no difference in alpha diversity (a measure of microbiome diversity within a sample) between the two treatment periods. This indicates that no bacterial species were extinguished by broccoli treatment. Beta diversity analysis (a measure of the (dis)similarity between samples) indicated that bacterial communities were impacted by treatment (P=0.03).
After broccoli consumption, Bacteroidetes increased by 10% (P =0.03), while Firmicutes decreased by 8% (P=0.05). Overall the ratio of Bacteroidetes to Firmicutes increased by 37% (P=0.01) versus a 5% decrease in the control period. The Bacteroides genus increased by 6% (P=0.02) versus a 2% decrease in the control period.
Interestingly, the effects were most strong in those with a lower BMI (< 26 kg/m2) who had an increase in metabolites after broccoli consumption. Algorithms to predict the function of the microbiota showed that broccoli increased endocrine (P=0.05), energy metabolism (P=0.01), transport and catabolism (P=0.04) pathways.
Conclusion
Broccoli intake, at 200g daily, changes the composition and potentially impacts the function of the gut microbiota.
Clinical practice applications:
- Studies like this allow practitioners to focus on specific foods in specific quantities to positively alter the microbiota and their function
- Cruciferous vegetables, like broccoli, kale, cauliflower, cabbage, Brussel sprouts, are an important group as they contain fibre and phytonutrients such as glucosinolates. These compounds can be metabolised by the microbiota into active compounds with health benefits. This study has shown the bidirectional benefit of broccoli consumption in that it can positively impact the function and composition of the microbiota
- Interestingly, the results in this small study were driven by participants with a BMI of less than 26. Sub-group analysis found no statistically significant relationships in participants with BMI >26
- It is worth noting that it is possible that the addition of 5g of fibre from the broccoli is also contributing to the changes observed.
Considerations for future research:
- Larger, controlled feeding studies that isolate specific foods to identify their effects on the microbiota are needed
- Genetic sequencing for only a few bacterial myrosinases has been completed and therefore future studies should aim to assess the metabolic capabilities in faecal samples such as myrosinase activity
- While this study and others have shown changes in the types of bacteria after cruciferous vegetable consumption the consistency of results has been mixed potentially due to differing study designs and treatment dosages. Further studies to clarify and confirm these results would be beneficial
- To assess the function of the microbiota a predictive algorithm was used. This requires experimental confirmation by such methods as metabolite profiling and whole genome shotgun sequencing.
Abstract
The human gastrointestinal microbiota is increasingly linked to health outcomes; however, our understanding of how specific foods alter the microbiota is limited. Cruciferous vegetables such as broccoli are a good source of dietary fiber and phytonutrients, including glucosinolates, which can be metabolized by gastrointestinal microbes. This study aimed to determine the impact of broccoli consumption on the gastrointestinal microbiota of healthy adults. A controlled feeding, randomized, crossover study consisting of two 18-day treatment periods separated by a 24-day washout was conducted in healthy adults (n=18). Participants were fed at weight maintenance with the intervention period diet including 200 g of cooked broccoli and 20 g of raw daikon radish per day. Fecal samples were collected at baseline and at the end of each treatment period for microbial analysis. Beta diversity analysis indicated that bacterial communities were impacted by treatment (P=.03). Broccoli consumption decreased the relative abundance of Firmicutes by 9% compared to control (P=.05), increased the relative abundance of Bacteroidetes by 10% compared to control (P=.03) and increased Bacteroides by 8% relative to control (P=.02). Furthermore, the effects were strongest among participants with body mass index <26 kg/m2, and within this group, there were associations between bacterial relative abundance and glucosinolate metabolites. Functional prediction revealed that broccoli consumption increased the pathways involved in the functions of the endocrine system (P=.05), transport and catabolism (P=.04), and energy metabolism (P=.01). These results reveal that broccoli consumption affects the composition and function of the human gastrointestinal microbiota.
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Dietary Diversity Was Positively Associated with Psychological Resilience among Elders: A Population-Based Study.
Yin, Z, Brasher, MS, Kraus, VB, Lv, Y, Shi, X, Zeng, Y
Nutrients. 2019;11(3)
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There's a growing interest by researchers in the relationship between the diversity of people's diets and their health, including their psychological resilience. This study looked at the associations between dietary diversity (DD) and psychological resilience in 8571 elderly individuals in China. Frequency and variety of food groups was collected in order to produce an average (mean) DD score. The psychological resilience of participants was assessed using a validated research tool known as "simplified resilience score" (SRS). The statistical analysis of the data collected showed that those elders with the poorest psychological resilience scores were also eating the least diverse diets. Based on separate analyses by age group, the association of a low SRS with poor DD was more prominent in the younger elderly than the oldest old. Compared with younger participants with good DD, the risk of a low SRS was greater for younger participants with poor DD, the oldest old with good DD, and the oldest old with poor DD, with OR respectively. The greatest contribution to DD was from a high consumption of vegetables, fruits, and nuts. Our study suggested that poor DD was associated with a low psychological resilience among the Chinese elderly, especially the younger elderly. These findings suggest that eating a diet rich in a variety of vegetables, fruits, and nuts might promote psychological resilience.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dietary polyphenols abundant in fruits, vegetables and nuts have been associated with improved psychological resilience.
- Healthcare practitioners working on the dietary diversity of their clients should focus attention on these phenolic-rich foods in the interests of psychological resilience.
Evidence Category:
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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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X
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 population-based study involving 8571 community-based elderly individuals, where dietary diversity (DD) was assessed by means of food frequency questionnaires, and correlated with psychological resilience, assessed by a validated simplified resilience score (SRS). Low DD has been previously correlated with a high level of oxidative stress mediating oxidative damage to mitochondria and lipids in neuronal circuits, as seen in affective (anxiety, depression) and neurodegenerative conditions (Alzheimer's and Parkinson's Diseases). Conversely, dietary polyphenols, a group of phenolic compounds abundant in fruits, vegetables, and other plant sources, have been associated with improved psychological resilience.
Clinical practice applications:
The greatest contribution to dietary diversity from the totality of food groups was from a high consumption of vegetables, fruits, and nuts. This can help nutrition practitioners inform their clinical decisions when supporting individuals wanting to improve the diversity of their diet.
Considerations for future research:
Future work is necessary to further assess these findings in longitudinal studies and clinical trials, and to ascertain what the mechanisms of action are in this process. It would be particularly interesting to find out whether the gut microbiota and its communication with the brain via the gut-brain axis is part of the process.
Abstract
The association between dietary diversity (DD) and psychological resilience among older people is an underdeveloped area of research. This cross-sectional study explored the associations of DD with psychological resilience among 8571 community-based elderly individuals. The intake frequencies of food groups were collected, and dietary diversity was assessed based on the mean DD score. Psychological resilience was assessed using a simplified resilience score (SRS). Data were analyzed using multiple linear regression and logistic regression models. Poor DD was significantly associated with psychological resilience, with a β (95% CI) of -0.94 (-1.07, -0.81) for the SRS (p < 0.01) and an odds ratio (95% CI) of 1.83 (1.66, 2.01) for low SRS status. The interaction effects of age with DD were observed for the SRS (p < 0.001) and low SRS status (p < 0.001). Based on separate analyses by age group, the association of a low SRS with poor DD was more prominent in the younger elderly than the oldest old, with OR (95% CI) 2.32 (1.96, 2.74) and 1.61 (1.43, 1.82), respectively. Compared with younger participants with good DD, the risk of a low SRS was greater for younger participants with poor DD, the oldest old with good DD, and the oldest old with poor DD, with OR (95% CI) 2.39 (2.02, 2.81), 1.28 (1.09, 1.51), and 2.03 (1.72, 2.39), respectively. The greatest contribution to DD was from a high consumption of vegetables, fruits, and nuts. Our study suggested that poor DD was associated with a low psychological resilience among the Chinese elderly, especially the younger elderly. These findings suggest that augmentation of DD might promote psychological resilience.
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Effect of 12-Week Daily Intake of the High-Lycopene Tomato (Solanum Lycopersicum), A Variety Named "PR-7", on Lipid Metabolism: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.
Nishimura, M, Tominaga, N, Ishikawa-Takano, Y, Maeda-Yamamoto, M, Nishihira, J
Nutrients. 2019;11(5)
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Tomatoes are a rich source of lycopene, a compound believed to have many health benefits. Researchers in Japan conducted a randomised, double-blind, placebo-controlled trial to investigate the effects of eating a type of tomato bred to be high in lycopene on 74 healthy volunteers with raised cholesterol levels. Participants were given 50g per day of either semi-dried high-lycopene tomato or lycopene-free tomato. Those eating the high-lycopene tomatoes significantly reduced their levels of LDL cholesterol over 12 weeks. The researchers concluded that their findings support the health benefits of eating tomatoes rich in lycopene.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Lycopene, a carotenoid, has antioxidant effects and exhibits the highest physical quenching rate constant for singlet oxygen.
- Lycopene has also been reported to inhibit the production of serum lipid peroxide and oxidize low-density lipoprotein (LDL)
- This study reported that the intake of 50g of high-lycopene (lycopene, 22.0-27.8mg) for 12 weeks significantly decreased LDL-C in subjects with LDL-C ranging from 120–139 mg/dL.
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:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group study was conducted to investigate the effects of the regular and continuous intake of high-lycopene tomato, a variety named PR-7, for 12 weeks on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels > 120 to <160mg/dL.
The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50g of semi-dried PR-7 (lycopene, 22.0-27.8mg) per day. Medical interviews were conducted, vital signs were monitored, and blood and saliva samples were taken at 0 (baseline) and at 4, 8 and 12 weeks.
Primary clinical outcomes were:
- The intake of high-lycopene tomato improved LDL-C at week 12 when compared to the placebo group (Week 12: placebo, 4,1 +- 15.7mg/dL; high-lycopene tomato, -3.7 +- 13.8.mg/dL; p=0.027).
- Based on a subgroup analysis, the ingestion of high-lycopene tomato significantly decreased LDL-C in subjects with LDL-C ranging from 120–139 mg/dL at week 12 (Week 12: placebo, 4.3 15.1 mg/dL; high-lycopene tomato, +- 5.1 9.5 mg/dL; p = 0.030).
Secondary clinical outcomes were:
- There were no significant differences between the high-lycopene tomato and placebo groups in terms of lipid profiles comprising of total cholesterol (TC), HDL-C, triglycerides (TG), LDL-C/HDL-C ratio, and non-HDL, and adiponectin.
- The intake of high-lycopene tomato increased lycopene levels compared to the placebo group (Week 12: placebo,
+-24.2 49.3 g/dL; high-lycopene tomato, 22.7 47.9 g/dL; p < 0.001).
- In addition, beta-carotene levels increased in the high-lycopene tomato group compared to those in the placebo group at week 12 (Week 12: placebo, 0.9 13.6 g/dL; high-lycopene tomato, 12.0 24.5 g/dL; p = 0.009).
Clinical practice applications:
- A previous meta-analysis demonstrated that LDL-C decreases when more than 25 mg per day of lycopene is ingested. The biological mechanism was associated with a reduction in 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase activity in the liver, activation of LDL-receptors, and increased expression of the ABCA1 transporter gene, the key component of HDL-C production.
- This study also suggests that there is a decrease in LDL-C at 12 weeks in subjects with LDL-C ranging from 120–139 mg/dL.
- Based on these findings, a practitioner could therefore consider recommending 25mg of lycopene to help reduce LDL-C in patients with an LDL-C range of 120–139 mg/dL for at least 12 weeks.
Considerations for future research:
- Lycopene has been reported to possess the strongest singlet oxygen scavenging ability among the eight carotenoids, as measured by the singlet oxygen absorption capacity method, and some researchers have found that lycopene and tomato display antioxidant effects. However, other reports suggest that ingesting lycopene does not affect oxidative markers. These findings suggest that further investigation is needed to evaluate the effect of lycopene on oxidative markers.
- The LOX index is a biomarker for the early risk of arteriosclerosis, cerebral infarction, and myocardial infarction. Lycopene might be ineffective against LOX-1 which is a product of the peroxidation reaction. Additional studies with a longer intake period are required to investigate the effect of lycopene on the risk of arteriosclerosis.
- The subjects in this study were asked to avoid cooking the test food (semi-dried tomato). It is, therefore, necessary to investigate the differences in the effect of the high-lycopene tomato based on various cooking methods.
Abstract
Tomato (Solanum lycopersicum) is a rich source of lycopene, a carotenoid that confers various positive biological effects such as improved lipid metabolism. Here, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study to investigate the effects of regular and continuous intake of a new high-lycopene tomato, a variety named PR-7, for 12 weeks, based on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels ≥120 to <160 mg/dL. The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50 g of semidried PR-7 (lycopene, 22.0-27.8 mg/day) each day for 12 weeks, while subjects in the placebo group ingested placebo semidried tomato. Medical interviews were conducted, vital signs were monitored, body composition was determined, and blood and saliva samples were taken at weeks 0 (baseline), 4, 8, and 12. The primary outcome assessed was LDL-C. The intake of high-lycopene tomato increased lycopene levels in this group compared to levels in the placebo group (p < 0.001). In addition, high-lycopene tomato intake improved LDL-C (p = 0.027). The intake of high-lycopene tomato, PR-7, reduced LDL-C and was confirmed to be safe.
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5.
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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Plain language summary
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.
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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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Plain language summary
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.
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Cardiovascular Health Benefits of Specific Vegetable Types: A Narrative Review.
Blekkenhorst, LC, Sim, M, Bondonno, CP, Bondonno, NP, Ward, NC, Prince, RL, Devine, A, Lewis, JR, Hodgson, JM
Nutrients. 2018;10(5)
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Diets high in vegetables are linked with a lower incidence of chronic disease. Some vegetables may have much larger health benefits in comparison to others, and therefore dietary guidelines could be developed to include targeted advice on consuming specific types of vegetables with the greatest health benefits. This review of observational studies focused on the cardiovascular health benefits of specific vegetable types. Vegetables discussed in this review were grouped into the following types: leafy green, cruciferous, alliums, yellow-orange-red and legumes. These vegetables contain many nutrients and phytochemicals that have been proposed to have benefits for cardiovascular health. The authors looked at the results from nearly 100 observational studies. Most of the studies were carried out on older adults; some were focussed on a single gender (male or female), and some were mixed. Follow up periods in the studies ranged from 3 years to 28 years. Most of the studies relied on food frequency questionnaires (FFQs) to estimate vegetable consumption, and many did not define the size of a vegetable portion in grams. The percentage of studies demonstrating significant benefits of vegetable consumption on CVD ranged from 25% for legumes to 43% for leafy greens. The strongest beneficial effects on CVD risk were seen for leafy green and cruciferous vegetables. The authors concluded that the evidence in this review suggests intake of leafy green and cruciferous vegetables may confer strong cardiovascular health benefits. Increasing vegetable intake, with a focus on leafy green and cruciferous vegetables may provide the greatest benefits.
Expert Review
Conflicts of interest:
Educator for various organizations, such as Institute for Functional Medicine, American Academy for Anti-Aging Medicine
Take Home Message:
- Green leafy vegetables and cruciferous vegetables were found to most impactful for cardiovascular health.
Evidence Category:
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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 review highlights the role of specific types of vegetables based on color and nutrients for cardiovascular health benefit.
Clinical practice applications:
The authors investigated whether some vegetable types were more relevant for cardiovascular-related issues than others. Based on their review of the scientific literature, green, leafy vegetables and cruciferous vegetables were found to be most impactful.
Considerations for future research:
This review suggests that more research is needed to understand how certain plant foods, vegetables, and phytochemicals may be functionally important for certain organ systems.
Abstract
Adequate vegetable consumption is one of the cornerstones of a healthy diet. The recommendation to increase vegetable intake is part of most dietary guidelines. Despite widespread and long-running public health messages to increase vegetable intake, similar to other countries worldwide, less than 1 in 10 adult Australians manage to meet target advice. Dietary guidelines are predominantly based on studies linking diets high in vegetables with lower risk of chronic diseases. Identifying vegetables with the strongest health benefits and incorporating these into dietary recommendations may enhance public health initiatives around vegetable intake. These enhanced public health initiatives would be targeted at reducing the risk of chronic diseases, such as cardiovascular diseases (CVD). Specific vegetable types contain high levels of particular nutrients and phytochemicals linked with cardiovascular health benefits. However, it is not clear if increasing intake of these specific vegetable types will result in larger benefits on risk of chronic diseases. This review presents an overview of the evidence for the relationships of specific types of vegetables, including leafy green, cruciferous, allium, yellow-orange-red and legumes, with subclinical and clinical CVD outcomes in observational epidemiological studies.
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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.
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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.