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The NED Journal - Edition 2
The NED Expert Review Journal is a quarterly production and includes nutrition and lifestyle science reviewed and relevant for integrative and personalised healthcare practice. The NED Journal supports BANT members and other integrative and personalised medicine practitioners with their evidence-based practice, transforming the science into individualised science-based decision making. Every quarter, expert reviews on new science are included, with a changing topic focus. Click the link to read online or download the pdf.
2024
Abstract
In this 2nd edition of the NED Expert Review Journal, you can read some of the latest expert insights on male health, ADHD and neurodiversity, and stress and adrenals. Also connect the NED Editorial Board and the members of the Expert Review Panel writing for this issue, with 14 research articles expertly reviewed.
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Benign Prostatic Hyperplasia - NED Infobite
BANT's scientific NED InfoBites are designed to provide key elements of the latest research using plain language. They provide quick overviews on particular health issues and nutrition topics for a speedy introduction to the science. Visually attractive and easily shareable with clients and social media followers.
2024
Abstract
Benign prostatic hyperplasia (BPH) is a common benign disease in middle-aged and elderly men which causes lower urinary tract symptoms. Age, sex hormones, diet, diabetes, obesity and genetic factors are closely related to BPH occurence. This NED Infobite presents science on obesity and lifestyle factors on the risk of BPH, the impacts of diabetes mellitus on lower urinary tract symptoms in BPH, the impact of testosterone on lower urinary tract symptoms and gene associations.
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Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.
Muehlenbein, M, Gassen, J, Nowak, T, Henderson, A, Morris, B, Weaver, S, Baker, E
American journal of men's health. 2023;17(2):15579883221130195
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A growing body of research finds that in men, testosterone levels may be prognostic of clinical outcomes related to coronavirus disease 2019 (COVID-19 disease). The presence of pre-existing chronic conditions in many patients with COVID-19 disease further complicates the relationship among testosterone and severe outcomes. The aim of this study was to examine whether pre-existing conditions for severe COVID-19 disease were related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This study obtained data from men (n = 142) who participated in the longitudinal study Waco COVID Survey. All data included in the study was collected as part of the initial intake survey and first laboratory appointment. Results show that serum-free testosterone levels decreased as a function of age. In fact, greater burden of pre-existing conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. Furthermore, in men older than 40 years of age the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Authors conclude that their findings add important insights into the complex role of androgens in chronic and infectious diseases and contribute to the growing body of literature on the relationship between chronic disease and men’s testosterone levels.
Abstract
Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease. The present project examines whether preexisting conditions for severe COVID-19 disease were themselves related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A clinical risk score for severe COVID-19 disease was computed based on the results of previously published meta-analyses and cohort studies, and relationships between this score and testosterone levels were tested in 142 men ages 19 to 82 years. Greater burden of preexisting conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. In older men, the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Given that older age itself is a predictor of COVID-19 disease severity, these results together suggest that the presence of preexisting conditions may confound the relationship between testosterone levels and COVID-19 disease outcomes in men. Future research examining relationships among testosterone and outcomes related to infectious and chronic diseases should consider potential confounds, such as the role of preexisting conditions.
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Fasting, Hormones and Menopause: Why women need a different approach to men
Rangan Chatterjee is a medical doctor with over 16 years experience who takes a 360° approach to health by focussing on 4 pillars of health: Food, Movement, Sleep and Relaxation. He is the founder and host of the Feel Better, Live More Podcast. My goal is to empower you to become the architect of your own health. I believe that when we are healthier, we are happier because when we feel better, we live more.
2023
Abstract
Dr Chatterjee chats to Mindy Pelz, a nutrition expert and pioneer on the subject of women’s health, hormones and fasting. Mindy outlines the hormonal differences between men and women, the hormonal changes experienced during each phase of a women’s menstrual cycle and how we can tailor almost anything such as diet, social life, exercise and cognition to harness the power of these hormones. They also explore fasting, the nuances around this from a hormonal perspective and how and when to integrate this into our cycle and at different life stages to achieve maximum benefits.
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Fasting, Hormones, and Men’s Sexual Health
As the pioneer and global leader of Functional Medicine, the Institute of Functional Medicine leads and catalyses the efforts of a large and expanding Functional Medicine ecosystem, including providers, educators, payers, industry leaders, regulators, and influencers.
2023
Abstract
IFM practitioner Mark Holthouse discusses male hormone dysregulation, specifically low testosterone and the impact that this might have on men’s sexual health and function. They explore lifestyle factors such as stress, sleep and body composition on testosterone levels; the metabolic pathways that might lower testosterone such as intestinal permeability, insulin resistance and aromatase upregulation, and how to mitigate this via intermittent fasting, phytonutrient intake and strength training to name a few.
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Men’s Health for Physical Performance and Longevity
The Functional Health Podcast is hosted by Ben Atkinson, a nutritionist with the core belief that a holistic and functional approach to health is fundamental to optimal well-being. The podcast promotes the integration and collaboration of conventional, complementary and allied health professionals in order to prosper in the changing landscape of healthcare.
2023
Abstract
Rick Miller is a clinical and sports dietician who is trained in functional medicine. In this podcast he eloquently explores optimal nutrition and exercise for men to support physical performance and longevity. He discusses the nuances around men and masculinity and how men are less likely to seek support for whole host of common issues such as insulin resistance, mental health, gastric concerns and sexual dysfunction. Interestingly, dopamine excess has been shown to impact libido and he manages this via a dopamine fast and cold exposure. Rick reviews the evidence around macronutrients on testosterone levels and explains his rationale for using an animal based eating approach within his clinic.
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Molecular Regulators of Muscle Mass and Mitochondrial Remodeling Are Not Influenced by Testosterone Administration in Young Women.
Horwath, O, Moberg, M, Hirschberg, AL, Ekblom, B, Apró, W
Frontiers in endocrinology. 2022;13:874748
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Testosterone is a sex hormone normally found in higher amounts in adult males than females. Testosterone plays a number of important roles, including influencing muscle size and strength. Treatment with testosterone has been shown to increase lean mass and muscle strength in women as well as men. However, female-only studies are limited, and the precise mechanisms underlying these changes are not well understood. This randomised control trial examined the effect of testosterone administration on regulators of muscle protein turnover and mitochondrial function in muscle samples collected from young women. 48 healthy, pre-menopausal women were assigned to receive either 10mg of transdermal testosterone gel per day, or a placebo, for 10 weeks. Muscle samples were collected via biopsy before and after the intervention. Testosterone administration did not appear to have a significant effect on androgen receptors, 5-alpha reductase, anabolic signalling, or mitochondrial remodelling in muscle tissue. The researchers concluded that improvements in muscle size and oxidative capacity following testosterone administration cannot be explained by changes in protein expression related to muscle protein turnover or mitochondrial remodelling. The authors went on to suggest that the small sample size in this study may have reduced the ability to detect small but biologically relevant changes in protein levels. Within the research, there is large variability among studies in terms of sex, age, route of administration and length of treatment, which makes putting these findings into context of the wider literature difficult.
Abstract
Testosterone (T) administration has previously been shown to improve muscle size and oxidative capacity. However, the molecular mechanisms underlying these adaptations in human skeletal muscle remain to be determined. Here, we examined the effect of moderate-dose T administration on molecular regulators of muscle protein turnover and mitochondrial remodeling in muscle samples collected from young women. Forty-eight healthy, physically active, young women (28 ± 4 years) were assigned in a random double-blind fashion to receive either T (10 mg/day) or placebo for 10-weeks. Muscle biopsies collected before and after the intervention period were divided into sub-cellular fractions and total protein levels of molecular regulators of muscle protein turnover and mitochondrial remodeling were analyzed using Western blotting. T administration had no effect on androgen receptor or 5α-reductase levels, nor on proteins involved in the mTORC1-signaling pathway (mTOR, S6K1, eEF2 and RPS6). Neither did it affect the abundance of proteins associated with proteasomal protein degradation (MAFbx, MuRF-1 and UBR5) and autophagy-lysosomal degradation (AMPK, ULK1 and p62). T administration also had no effect on proteins in the mitochondria enriched fraction regulating mitophagy (Beclin, BNIP3, LC3B-I, LC3B-II and LC3B-II/I ratio) and morphology (Mitofilin), and it did not alter the expression of mitochondrial fission- (FIS1 and DRP1) or fusion factors (OPA1 and MFN2). In summary, these data indicate that improvements in muscle size and oxidative capacity in young women in response to moderate-dose T administration cannot be explained by alterations in total expression of molecular factors known to regulate muscle protein turnover or mitochondrial remodeling.
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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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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).
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Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.
Hudson, J, Cruickshank, M, Quinton, R, Aucott, L, Aceves-Martins, M, Gillies, K, Bhasin, S, Snyder, PJ, Ellenberg, SS, Grossmann, M, et al
The lancet. Healthy longevity. 2022;3(6):e381-e393
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Hypogonadism is caused by testosterone deficiency and results in diminished sexual function, muscle wastage, weakness, osteoporosis, and reduced quality of life. Testosterone supplementation is used as a therapy for hypogonadism but there is some doubt on its safety, and it may come with serious side effects such as heart attacks. This systematic review and meta-analysis aimed to determine the effect of testosterone supplementation on heart health. The results showed that heart disease risk was unaffected by testosterone supplementation and there was a trend for fewer deaths following treatment. It was concluded that testosterone did not affect short-medium-term heart attack risk, however there was a lack of evidence in the long-term. This study could be used by healthcare professionals to understand that testosterone supplementation may be of benefit to individuals who need it without increasing their risk for heart attacks.
Abstract
BACKGROUND Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. METHODS We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. FINDINGS 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. INTERPRETATION We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. FUNDING National Institute for Health Research Health Technology Assessment Programme.