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Associations between circulating obesity-related biomarkers and prognosis in female breast cancer survivors: a systematic review of observational data in women enrolled in lifestyle intervention trials.
Meyer, D, Pastor-Villaescusa, B, Michel, S, Hauner, H, Hauner, D
BMC cancer. 2022;22(1):1187
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Overweight and obesity play a role in the development and potential outcomes in breast cancer. Several factors have been implicated linking cancer and obesity including hormones imbalances and inflammation, however exact links have yet to be elucidated. This systematic review of 4 randomised control trials containing 5234 women aimed to examine obesity related blood factors such as hormones, fats and sugar and their relationship with prognosis in individuals with breast cancer. The results showed that higher levels of testosterone were associated with an increased risk of recurrence of breast cancer. The female sex hormones, oestradiol and sex hormone binding globulin were not associated with breast cancer recurrence. Blood sugar levels and insulin resistance were not associated with breast cancer recurrence. There were certain growth factors, which are molecules responsible for stimulating cellular processes, that were responsible for an increased chance of recurrence of breast cancer and insulin-like growth factor and platelet derived growth factor were shown to increase risk but only when increased in combination with each other. Inconsistent results were seen with C-reactive protein, which is an inflammatory marker. It was concluded that testosterone may be associated with an increased risk of breast cancer recurrence, however the evidence from the other blood factor was unreliable due to poor quality trials. More trials are needed to investigate these factors further. This study could be used by healthcare professionals to understand that weight loss is the key to the prevention of recurrence of breast cancer in those who are overweight and that testosterone levels could be used to identify those who are at an increased risk.
Abstract
Obesity plays an important role in the development and progression of breast cancer via various oncogenic pathways. However, the biological mechanisms underlying this relationship are not fully understood. Moreover, it is unclear whether obesity-related and further associated biomarkers could be suitable targets for lifestyle interventions. This systematic review was conducted to examine relationships between obesity-related blood parameters and prognosis for breast cancer survivors enrolled in lifestyle intervention studies. A systematic, computerized literature search was conducted from inception through August 26th, 2020 in PubMed, EMBASE, and CENTRAL. The focus was on observational data from randomized controlled lifestyle intervention trials investigating associations between selected baseline biomarkers, measured in remission, and breast cancer recurrence, breast cancer mortality and/or all-cause mortality. Four studies with data from 5234 women met the inclusion criteria.Studies herein provide moderate evidence that bioavailable or serum testosterone may be positively linked to breast cancer recurrence and inversely linked to disease-free survival. Limited evidence suggests no associations with circulating estradiol or insulin levels on prognosis outcomes, whereas HDL cholesterol was inversely associated with breast cancer recurrence. For some other biomarkers, such as growth factors, adipokines, and CRP, the evidence for associations with disease prognosis was too weak to draw conclusions.Overall, despite potential candidates, there is insufficient evidence to confirm or refute that obesity-related biomarkers and sex hormones have a prognostic value for breast cancer survival. More longitudinal studies in breast cancer survivors to examine the clinical utility of obesity-related biomarkers are needed.
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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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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).
3.
The impact of nutrition and lifestyle on male fertility.
Benatta, M, Kettache, R, Buchholz, N, Trinchieri, A
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2020;92(2)
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The impact of environmental, lifestyle and nutritional factors on unexplained male fertility has long been acknowledged. Yet, little research had been dedicated to the topic, despite declining semen quality having become a worldwide phenomena. Available studies have yielded limited, and at times conflicting, evidence. Hence this literature review sought to capture the current knowledge around unexplained male infertility and environmental, lifestyle, diet and nutrients factors. Summarized is the evidence from 69 studies, including population observations and clinical trials. The collected outcomes showed that a Western-type diet, rich in red and processed meats, refined grains, high-energy drinks and sweets, trans and saturated fats was associated with poor semen quality. Whereby higher intakes of fruits and vegetables, whole grains, omega-3 and poultry showed beneficial effects. However, as only selected groups were examined, more research is needed to project such findings onto the wider population. The reviewed evidence also included alcohol consumption, which showed high alcohol intake closely correlated to declining sperm concentrations. Whilst the verdict on caffeine consumption and the impact on sperm quality was inconclusive. In addition, several interventional studies evaluated the effect of dietary supplementation on various parameters of semen, where coenzyme Q10, L-carnitine, vitamin E, antioxidants, combined nutrient formulations and herbal blends all had positive outcomes. The review on zinc and folic acid supplementation yielded mixed results. This brief recap of the current evidence on environmental, lifestyle and nutritional influences on male infertility summarises the dietary foundations for the support of unexplained male infertility.
Abstract
BACKGROUND AND AIMS Male unexplained infertility has long been suspected to result from environmental, lifestyle and nutritional factors. However, the literature on the subject is still scarce, and clinical studies providing robust evidence are even scarcer. In addition, some similar studies come to different conclusions. Dietary pattern can influence spermatogenesis by its content of fatty acids and antioxidants. Yet, in an age of industrialized mass food production, human bodies become more exposed to the ingestion of xenobiotics, as well as chemicals used for production, preservation, transportation and taste enhancement of foods. We attempted in this paper to collect the available evidence to date on the effect of nutritional components on male fertility. MATERIAL AND METHODS A systematic search of the relevant literature published in PubMed, ScienceDirect and Cochrane Central Register of Controlled Trials Database was conducted. Literature was evaluated according to the Newcastle-Ottawa- Scale. RESULTS Epidemiological observations are concordant in demonstrating an association of low-quality sperm parameters with higher intake of red meat, processed and organ meat and fullfat dairy. On the contrary, better semen parameters were observed in subjects consuming a healthy diet, rich in fruit, vegetables, whole grains and fish. Evidences of the negative impact on male fertility of by-products of water disinfection, accumulation in food chain of persistent organochlorine pollutants, pesticides, phthalates from food and water containers and hormones used in breeding cattle have been reported. Clinical trials of the effects of micronutrients on semen parameters and outcomes of assisted fertilization are encouraging, although optimal modality of treatment should be established. CONCLUSIONS Although quality of evidence should be ameliorated, it emerges that environmental factors can influence male fertility. Some nutrients may enhance fertility whereas others will worsen it. With diagnostic analysis on a molecular or even sub-molecular level, new interactions with micronutrients or molecular components of our daily ingested foods and leisure drugs may lead to a better understanding of so far suspected but as yet unexplained effects on male spermatogenesis and fertility.