1.
Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.
Whittaker, J, Harris, M
Nutrition and health. 2022;28(4):543-554
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Plain language summary
Testosterone is the primary male sex hormone, and vital for reproductive development and function. Moreover, low endogenous testosterone is associated with an increased risk of chronic disease, including type 2 diabetes and cardiovascular disease. The aim of this study was to investigate the effects of low- versus high-carbohydrate diets on mens' testosterone and cortisol. This study is a systematic review and meta-analysis of twenty-seven studies with a total of 309 participants. Twelve of these studies were randomised trials whilst the rest were non-randomised. Results show an increase in resting and post-exercise cortisol on short-term low-carbohydrate diets (<3 weeks). In fact, resting cortisol levels return to baseline after <3 weeks on a LC diet, whilst post-exercise cortisol remains elevated. Furthermore, high-protein diets cause a large decrease in resting total testosterone. Authors conclude that further research is required in order to warrant their findings.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short-term LC-diets diets cause a moderate increase in resting and post-exercise cortisol however this effect is not seen in LC-diets followed for great than 3 weeks
- HP-LC diets caused a statistically significant decrease in resting TT, suggesting caution in relation to endocrine effects of LC diets
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:
A systematic review and network meta-analysis was conducted on the effects of low-carbohydrate (LC) versus high-carbohydrate (HC) diets on men’s testosterone and cortisol.
The review was registered with PROSPERO and reported using PRISMA 2020 checklists.
Methods:
A comprehensive search strategy was used to find intervention studies looking at healthy adult males and LC diets of <35% carbohydrate. Studies were assessed for quality using the Cochrane Risk of Bias tool. Sub-group analyses was conducted for diet duration, protein intake and exercise duration.
Results:
The literature search resulted in 27 studies with a total of 309 healthy adult male participants, age: 27.3 ± 4.7 (to minimise variation in steroid hormone metabolism), body mass: 78.6± 7.1kg and BMI: 24.8 ±1.6. 12 randomised and 15 non-randomised controlled trials were analysed. 21 studies were considered low risk bias, 5 medium and 1 high risk.
- Short-term (<3 weeks) LC diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01) when compared to HC diets.
- Long-term (≥3 weeks) LC diets had no consistent effect on resting cortisol
- LC diets resulted in higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01).
- The overall results for resting total testosterone (TT) showed a significant decrease on LC versus HC diets (SMD = −0.48, p = 0.01. However, subgroup analyses revealed this effect to be limited to high-protein (HP) LC diets, which yielded a very large decrease in TT (SMD = −1.08, p < 0.01; ∼5.23 nmol/L), albeit in a small sample (n = 26).
- Moderate protein (MP) (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05).
- There was no overall effect of LC versus HC diets on 0 h post-exercise TT (SMD = −0.03, p = 0.95). However, subgroup analysis showed 0 h post-exercise was non-significantly higher on long-term LC versus HC diets (SMD = 0.44, p = 0.18), and much lower on short-term LC versus HC diets (SMD = −1.01, p = 0.05)
Conclusion:
This systematic review and metanalysis found an increase in resting and post-exercise cortisol on short-term LC diets. Cortisol does return to baseline in the first 3 weeks of a low-carbohydrate (LC) diet. The same response is, however, not seen in post-exercise cortisol, which remains elevated. In addition, the review showed that compared to moderate-protein diets, HP diets were found to cause a large decrease in resting and post-exercise TT (∼5.23 nmol/L).
Clinical practice applications:
The results of this review suggest that exercising whilst following a LC diet can increase cortisol in the short term, but not long-term. This suggests a period of diet adaptation. The effects of long-term LC diets on cardiovascular disease risk is uncertain and healthcare practitioners should monitor client responses and keep up-to-date with new research in this area
Since HP-LC diets were found to significantly decrease resting testosterone it highlights the need to ensure that protein intake does not exceed the urea cycle’s capacity due to potential adverse endocrine effects.
For clients where there is a desire to increase strength, power and hypertrophy, a MP-LC diet could be of benefit, as it showed potential to signal an increased anabolic state post exercise..
NB: Since the review only included a low number of studies and saw within these some heterogeneity that could not be explained, more research is needed before the paper’s findings can be conclusive. The above potential practice applications should therefore be seen as something to be mindful of when working with clients where cortisol and testosterone levels are relevant to their protocol.
Considerations for future research:
Future research should consider:
- Since LC diets have been shown to have a positive effect on health – decreased triglycerides, increased high density lipoprotein cholesterol and weight loss - future studies would benefit from including these markers so any positive and negative impacts can be monitored directly.
- Despite extensive analysis including sensitivity analysis to reduce bias and heterogeneity of the results, the paper highlights a need for further research to ensure consistency in key parameters e.g., exercise duration and intensity, carbohydrate supplements inclusion and period of dietary intervention. Since it was identified that HP-LP diets impact post exercise and resting TT, follow up studies would benefit from consistency in participants diets. This would help to reduce any potential confounding results.
Abstract
Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (-1.08 [-1.67, -0.48], p < 0.01) and post-exercise total testosterone (-1.01 [-2, -0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
2.
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.