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Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 'long-haulers'?
Wood, E, Hall, KH, Tate, W
Chronic diseases and translational medicine. 2021;7(1):14-26
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Cases of chronic fatigue have been reported following recovery from Covid-19, in what is termed ‘Long Covid’, with symptoms likened to that of sufferers from chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME). How CFS/ME develop and treatments may help to further understand Covid-19. This review study of 111 studies aimed to identify where urgent research is required to help understand the potential of chronic fatigue therapies in Covid-19. The study first reviewed disrupted cellular energy production in ME/CFS and increased presence of damaging oxidants. Current therapies for improving cellular energy production in CFS/ME were then reviewed and Ritalin, ubiquinone and mitoquinol mesylate were heavily featured. Antioxidant therapies in CFS/ME were reviewed and observations would suggest that trials in patients with long covid are needed. It was concluded that research in cellular energy production in CFS/ME has been increasing, however remains contradictory due to a lack of a definitive diagnosis, differing disease severity and the huge differences between patients who suffer from CFS/ME. Further research is required in ME/CFS and Covid-19. This study could be used by health care professionals to understand the importance of monitoring symptoms of fatigue post Covid-19 infection and the possible use of ME/CFS treatments.
Abstract
A significant number of SARS-CoV-2 (COVID-19) pandemic patients have developed chronic symptoms lasting weeks or months which are very similar to those described for myalgic encephalomyelitis/chronic fatigue syndrome. This study reviews the current literature and understanding of the role that mitochondria, oxidative stress and antioxidants may play in the understanding of the pathophysiology and treatment of chronic fatigue. It describes what is known about the dysfunctional pathways which can develop in mitochondria and their relationship to chronic fatigue. It also reviews what is known about oxidative stress and how this can be related to the pathophysiology of fatigue, as well as examining the potential for specific therapy directed at mitochondria for the treatment of chronic fatigue in the form of antioxidants. This study identifies areas which require urgent, further research in order to fully elucidate the clinical and therapeutic potential of these approaches.
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Western Dietary Pattern Antioxidant Intakes and Oxidative Stress: Importance During the SARS-CoV-2/COVID-19 Pandemic.
Trujillo-Mayol, I, Guerra-Valle, M, Casas-Forero, N, Sobral, MMC, Viegas, O, Alarcón-Enos, J, Ferreira, IM, Pinho, O
Advances in nutrition (Bethesda, Md.). 2021;12(3):670-681
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The Atlantic diet (AD), Mediterranean diet (MD) and diets which follow the American dietary guidelines (AmD) all supply enough nutrients for the body to stay healthy. However, during periods of viral pandemics, such as the Covid-19 pandemic, these diets may be inadequate for optimal resistance to infection. Furthermore, nutrient requirements may alter with age, stress, and health. This review paper aimed to discuss the three different diets and their suitability depending on age and physical and mental state. Supplementation during a pandemic was also discussed. When the body contracts viruses such as Covid-19, reactive oxygen species can accumulate resulting in oxidative stress which can damage the cells. Nutrients in the diet, which act as antioxidants may be of benefit, in this instance, however traditional balanced diets such as the AD, MD and AmD may be inadequate. In tandem with a balanced diet, supplementation may improve health. Zinc, vitamin A, selenium, vitamin D, vitamin C, and iron have been shown in research to improve the body’s response to viruses. It was concluded that the Covid-19 pandemic has caused severe infections, which can result in oxidative stress, increasing vulnerability to viral infections. Supplementing certain nutrients may be of benefit especially in vulnerable individuals. This study could be used by healthcare professionals to understand that a balanced diet is essential during viral pandemics, and it may be necessary to consider supplementation for high-risk individuals.
Abstract
The importance of balanced dietary habits, which include appropriate amounts of antioxidants to maintain the immune system, has become increasingly relevant during the current SARS-CoV-2/COVID-19 pandemic, because viral infections are characterized by high oxidative stress. Furthermore, the measures taken by governments to control the pandemic have led to increased anxiety, stress, and depression, which affect physical and mental health, all of which are influenced by nutritional status, diet, and lifestyle. The Mediterranean diet (MD), Atlantic diet (AD), and the Dietary Guidelines for Americans all provide the essential vitamins, minerals, and phenolic compounds needed to activate enzymatic and nonenzymatic antioxidant responses. However, viral pandemics such as the current COVID-19 crisis entail high oxidative damage caused by both the infection and the resultant social stresses within populations, which increases the probability and severity of infection. Balanced dietary patterns such as the MD and the AD are characterized by the consumption of fruit, vegetables, legumes, olive oil, and whole grains with low intakes of processed foods and red meat. For a healthy lifestyle in young adults, the MD in particular provides the required amount of antioxidants per day for vitamins D (0.3-3.8 μg), E (17.0 mg), C (137.2-269.8 mg), A (1273.3 μg), B-12 (1.5-2.0 μg), and folate (455.1-561.3 μg), the minerals Se (120.0 μg), Zn (11.0 mg), Fe (15.0-18.8 mg), and Mn (5.2-12.5 mg), and polyphenols (1171.00 mg) needed to maintain an active immune response. However, all of these diets are deficient in the recommended amount of vitamin D (20 μg/d). Therefore, vulnerable populations such as elders and obese individuals could benefit from antioxidant supplementation to improve their antioxidant response. Although evidence remains scarce, there is some indication that a healthy diet, along with supplemental antioxidant intake, is beneficial to COVID-19 patients.
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Plant-Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application.
Li, HY, Gan, RY, Shang, A, Mao, QQ, Sun, QC, Wu, DT, Geng, F, He, XQ, Li, HB
Oxidative medicine and cellular longevity. 2021;2021:6621644
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Fatty liver disease is the accumulation of fats and inflammation associated with poor dietary patterns. Plant-based foods have been recommended to manage this disease and this review aimed to highlight the most recent data on the mechanisms for this. Beyond their obvious capabilities of being low in fat, plant-based foods may contain naturally occurring compounds that can help alleviate fatty liver disease through improved inflammation, improved gut microbiota and cellular changes. In support of this, clinical benefits on fatty liver outcomes have been reported in the research. There may be safety issues with isolating certain natural compounds from plant-based foods, which requires more research, however plant-based foods is a promising therapy for fatty liver disease.
Abstract
Fatty liver disease (FLD), including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), is a serious chronic metabolic disease that affects a wide range of people. Lipid accumulation accompanied by oxidative stress and inflammation in the liver is the most important pathogenesis of FLD. The plant-based, high-fiber, and low-fat diet has been recommended to manage FLD for a long time. This review discusses the current state of the art into the effects, mechanisms, and clinical application of plant-based foods in NAFLD and AFLD, with highlighting related molecular mechanisms. Epidemiological evidence revealed that the consumption of several plant-based foods was beneficial to alleviating FLD. Further experimental studies found out that fruits, spices, teas, coffee, and other plants, as well as their bioactive compounds, such as resveratrol, anthocyanin, curcumin, and tea polyphenols, could alleviate FLD by ameliorating hepatic steatosis, oxidative stress, inflammation, gut dysbiosis, and apoptosis, as well as regulating autophagy and ethanol metabolism. More importantly, clinical trials confirmed the beneficial effects of plant-based foods on patients with fatty liver. However, several issues need to be further studied especially the safety and effective doses of plant-based foods and their bioactive compounds. Overall, certain plant-based foods are promising natural sources of bioactive compounds to prevent and alleviate fatty liver disease.
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Effect of sleep duration on dietary intake, desire to eat, measures of food intake and metabolic hormones: A systematic review of clinical trials.
Soltanieh, S, Solgi, S, Ansari, M, Santos, HO, Abbasi, B
Clinical nutrition ESPEN. 2021;45:55-65
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Adequate sleep is crucial to health. Yet, sleep disturbances have become very common in modern societies. A lack of sleep is linked to increased risk for several chronic diseases such as diabetes, high blood pressure, metabolic syndrome and cardiovascular disease. Furthermore, appetite-regulating hormones can be disrupted by sleep shortages, which is thought to drive chronic overeating, leading to weight gain, obesity and its associated health consequences. This review examined the relationship between sleep duration and food consumption and energy intake, whilst also monitoring changes in body weight and appetite-regulating hormones. The review encompassed 50 randomized controlled trials (RCTs) with 3387 participants, including 1079 children and adolescents and 2308 adults. The findings suggested that sleep shortages contribute to significant increases in calorie intake, fat intake, increased body weight, appetite, hunger, more frequent eating and bigger portion sizes. In this review lack of sleep did not change protein and carbohydrate intake. Nor did lack of sleep make people exert more or less energy overall, however, a variance amongst ethnic groups was observed here. There was not enough evidence for changes in metabolic rate, so the review assumed no significant effect. When viewed collectively, the appetite-regulating hormones of leptin and ghrelin, the stress hormone cortisol and the sugar-regulating hormone insulin were not significantly influenced by sleep duration. However, there seemed to be a wide variance of outcomes when looking at individual studies' results. In conclusion, the authors reiterated the importance of sleep for health maintenance, advocating for a minimum of 7 hours of sleep per day for adults and that, despite busy modern lifestyles, sleep optimisation strategies should be prioritised. Less than 6 hours of sleep per day increases the risk of health consequences, like weight gain and metabolic disorders and sleep management should be considered part of their treatment protocols.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Reduced sleep duration may serve as a mediator for weight gain in part due to increased appetite, increased fat intake and disruptions to energy balance.
- Enhancing sleep quality may serve to support weight loss protocols.
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
Short sleep duration and disruptions to circadian rhythm have been associated with being overweight and obese. It has been suggested that sleep restriction may interfere with appetite regulating hormones leading to increased appetite and disrupted energy balance.
This study aimed to systematically review studies exploring the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics and appetite-regulating hormones.
Methods
This systematic review included 50 randomised controlled trials including 3,387 participants.
Results
Energy intake
- 13 out of 30 the included studies found that short sleep conditions led to higher energy intake.
- 1 study identified that sleep restriction resulted in a 15.3% and 9.2% increase in energy intake in both women and men.
- 3 studies noted that prolonging sleep duration led to a reduction in energy intake.
- 1 study reported a reduction in energy intake after sleep restriction (P=0.031).
Fat consumption
- 9 studies out of 22 identified a significant association between short sleep and increased fat consumption.
- 7 studies did not identify a difference between groups.
- 3 studies noted a decrease in fat consumption following prolonged sleep (P<0.001, P<0.05, P=0.04).
Hunger and appetite
- 11 studies out of 17 observed that sleep restriction resulted in increased hunger ratings.
- 3 studies found an increase in appetite following sleep restriction (P<0.01) with 3 finding no difference..
- 1 study reported a decrease in appetite following sleep restriction.
- 2 studies noted that portion sizes increased as a result of sleep restriction (P<0.01).
- 1 study reported an increase in eating occasions following restricted sleep compared to habitual sleep (6.08 vs 4.96).
Body weight
- 6 studies out of 14 found no effect of sleep loss on body weight.
- 4 studies identified that sleep restriction led to weight gain (P<0.001, P<0.05, P=0.14, P=0.031).
- 2 studies reported weight loss following increased sleep duration (P<0.001).
Ghrelin and leptin
- Leptin and ghrelin levels were generally not found to be influenced by sleep duration, with the exception of a few studies.
Clinical practice applications:
Reduced sleep duration may promote weight gain by:
- Increasing energy intake.
- Increasing fat consumption.
- Increasing hunger and appetite.
- Increasing portion sizes and eating occasions.
Prolonging sleep duration may support weight loss by:
- Reducing energy intake.
- Reducing fat intake.
Considerations for future research:
- Mixed results on the influence of sleep restriction on appetite regulating hormones, leptin and ghrelin.
- Some studies noted the negative impact of sleep restriction on leptin and ghrelin concentrations, collectively shortened sleep duration did not appear to influence these hormones.
- Further sleep restriction studies exploring additional appetite regulating hormones and neuropeptides and the reward system may provide a more definitive understanding of the underlying mechanism for reduced sleep duration to disrupt the appetite and energy balance and promote weight gain.
Abstract
BACKGROUND AND AIMS Sleep, as well as diet and physical activity, plays a significant role in growth, maturation, health, and regulation of energy homeostasis. Recently, there is increasing evidence indicating a possible causal association between sleep duration and energy balance. We aimed to examine the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics, and appetite-regulating hormones by randomized controlled trials (RCTs). METHODS Electronic literature searches were conducted on Medline, Web of Science, and Google Scholar until July 2020. The search was conducted with the following words: "Sleep Duration", "Circadian Rhythm", "Sleep Disorders" in combination with "Obesity", "Overweight", "Abdominal Obesity", "Physical Activity", "Energy Intake", "Body Mass Index", "Lipid Metabolism", "Caloric Restriction", Leptin, "Weight Gain", and "Appetite Regulation" using human studies.methods RESULTS After screening 708 abstracts, 50 RCTs (7 on children or adolescents and 43 on adults) were identified and met the inclusion criteria. In general, the findings suggested that sleep restriction may leads to a significant increment in energy intake, fat intake, body weight, appetite, hunger, eating occasions, and portion size, while protein and carbohydrate consumption, total energy expenditure, and respiratory quotient remained unaffected as a result of sleep restriction. Serum leptin, ghrelin, and cortisol concentrations were not influenced by sleep duration as well. CONCLUSION Insufficient sleep can be considered as a contributing factor for energy imbalance, weight gain, and metabolic disorders and it is suggested that to tackle disordered eating it may be necessary to pay more attention to sleep duration.
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Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans.
Nascimento, EBM, Moonen, MPB, Remie, CME, Gariani, K, Jörgensen, JA, Schaart, G, Hoeks, J, Auwerx, J, van Marken Lichtenbelt, WD, Schrauwen, P
The Journal of clinical endocrinology and metabolism. 2021;106(5):1437-1447
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Brown fat is a type of fat that burns energy to regulate the body’s temperature in cold conditions. A high level of activity in the brown fat has been associated with healthy whole-body metabolism. Several supplements have been investigated for their potential to activate brown fat, however many of these have limiting side effects. Nicotinamide riboside (NR), also known as vitamin B3, is a supplement which can boost energy burning pathways within the body. This randomised control trial was part of a larger trial including a study on human brown fat cells and aimed to determine whether NR supplementation in overweight and obese individuals may act on the activity of brown tissue. The results showed that 6 weeks of NR supplementation had no effect on brown tissue activity or energy expenditure. It was concluded that NR supplementation for 6 weeks in individuals with obesity had no effect on brown fat tissue for reasons unknown, as the cellular study showed an increase in activity. This study could be used by healthcare professionals to better understand the role of brown fat in metabolism.
Abstract
CONTEXT Elevating nicotinamide adenine dinucleotide (NAD+) levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high-fat-diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism, and enhanced cold tolerance. OBJECTIVE Because brown adipose tissue (BAT) is a major source of thermogenesis, we hypothesize that NR stimulates BAT in mice and humans. DESIGN AND INTERVENTION HFD-fed C56BL/6J mice were supplemented with 400 mg/kg/day NR for 4 weeks and subsequently exposed to cold. In vitro primary adipocytes derived from human BAT biopsies were pretreated with 50 µM or 500 µM NR before measuring mitochondrial uncoupling. Human volunteers (45-65 years; body mass index, 27-35 kg/m2) were supplemented with 1000 mg/day NR for 6 weeks to determine whether BAT activity increased, as measured by [18F]FDG uptake via positron emission tomography-computed tomography (randomized, double blinded, placebo-controlled, crossover study with NR supplementation). RESULTS NR supplementation in HFD-fed mice decreased adipocyte cell size in BAT. Cold exposure further decreased adipocyte cell size on top of that achieved by NR alone independent of ex vivo lipolysis. In adipocytes derived from human BAT, NR enhanced in vitro norepinephrine-stimulated mitochondrial uncoupling. However, NR supplementation in human volunteers did not alter BAT activity or cold-induced thermogenesis. CONCLUSIONS NR stimulates in vitro human BAT but not in vivo BAT in humans. Our research demonstrates the need for further translational research to better understand the differences in NAD+ metabolism in mouse and human.
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NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.
Connell, NJ, Grevendonk, L, Fealy, CE, Moonen-Kornips, E, Bruls, YMH, Schrauwen-Hinderling, VB, de Vogel, J, Hageman, R, Geurts, J, Zapata-Perez, R, et al
The Journal of nutrition. 2021;151(10):2917-2931
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Ageing is associated with the progressive loss of muscle, which can result in impaired movement, an increased risk for falls and disrupted energy production. During ageing there is a decrease in one of the substrates involved in producing energy known as NAD+. Studies in animals have shown that supplementing with a precursor of NAD+ promotes longevity and energy production. In humans supplementation with a precursor of NAD+ has been shown to improve heart health and be of benefit to individuals with obesity. This randomised control trial aimed to determine the effect of supplementing the NAD+ precursors, tryptophan, nicotinic acid, and nicotinamide on muscle function in 14 older adults with impaired physical function. The results showed that supplementation had no effect on NAD+ and had no effect on muscular energy production nor exercise performance following a cycling test. It was concluded that supplementation with an NAD+ precursor does not improve muscle function. This study could be used by healthcare professionals to understand that a combination supplement of tryptophan, nicotinic acid, and nicotinamide may not benefit the physical function of older adults.
Abstract
BACKGROUND Boosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function. OBJECTIVES We investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults. METHODS A randomized, double-blind, controlled trial was conducted in 14 (female/male: 4/10) community-dwelling, older adults with impaired physical function [age, 72.9 ± 4.0 years; BMI, 25.2 ± 2.3 kg/m2]. Participants were supplemented with 207.5 mg niacin equivalents/day [intervention (INT)] and a control product (CON) that did not contain niacin equivalents, each for 32 days. The primary outcomes tested were mitochondrial oxidative capacity and exercise efficiency, analyzed by means of paired Student's t-tests. Secondary outcomes, such as NAD+ concentrations, were analyzed accordingly. RESULTS Following supplementation, skeletal muscle NAD+ concentrations [7.5 ± 1.9 compared with 7.9 ± 1.6 AU, respectively] in INT compared with CON conditions were not significantly different compared to the control condition, whereas skeletal muscle methyl-nicotinamide levels were significantly higher under NAD+-precursor supplementation [INT, 0.098 ± 0.063 compared with CON, 0.025 ± 0.014; P = 0.001], suggesting an increased NAD+ metabolism. Conversely, neither ADP-stimulated [INT, 82.1 ± 19.0 compared with CON, 84.0 ± 19.2; P = 0.716] nor maximally uncoupled mitochondrial respiration [INT, 103.4 ± 30.7 compared with CON, 108.7 ± 33.4; P = 0.495] improved under NAD+-precursor supplementation, nor did net exercise efficiency during the submaximal cycling test [INT, 20.2 ± 2.77 compared with CON, 20.8 ± 2.88; P = 0.342]. CONCLUSIONS Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This study was registered at clinicaltrials.gov as NCT03310034.
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Moderate Consumption of Beer (with and without Ethanol) and Menopausal Symptoms: Results from a Parallel Clinical Trial in Postmenopausal Women.
Trius-Soler, M, Marhuenda-Muñoz, M, Laveriano-Santos, EP, Martínez-Huélamo, M, Sasot, G, Storniolo, CE, Estruch, R, Lamuela-Raventós, RM, Tresserra-Rimbau, A
Nutrients. 2021;13(7)
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During the menopause, hormonal changes can trigger uncomfortable symptoms such as hot flashes, night sweats, sleep disturbances, and vaginal dryness. Hormone replacement therapy does reduce some of the symptoms, however there has been an increased interest in alternative therapies such as phytoestrogens to relieve these symptoms. Phytoestrogens are compounds with oestrogen-like properties naturally found in plants. Beer is the main food source of the strongest phytoestrogen identified to date. The aim of this six-month parallel, controlled clinical intervention trial was to evaluate if a moderate daily intake of beer, with or without alcohol, could reduce menopausal symptoms in women. Female sex hormone profile and cardiovascular risk factors (CVRF) were also monitored. 34 postmenopausal women took part. One group included alcoholic beer (AB), and a second group added non-alcoholic beer (NAB) for 6 months. The control group took no alcohol in this time. After a 6-month follow-up both groups (AB and NAB) significantly reduced the severity of the menopause-related symptoms. These results must be considered as preliminary and will require confirmation with larger sample sizes.
Abstract
The menopausal transition can be a challenging period for women's health and a trigger of uncomfortable symptoms. Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, we evaluated if a daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors. A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups: 16 were administered AB (330 mL/day), 7 NAB (660 mL/day), and 14 were in the control group. After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms (p-value AB vs. Control: 0.009; p-value NAB vs. Control: 0.033). Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.
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An updated systematic review and meta-analysis on adherence to mediterranean diet and risk of cancer.
Morze, J, Danielewicz, A, Przybyłowicz, K, Zeng, H, Hoffmann, G, Schwingshackl, L
European journal of nutrition. 2021;60(3):1561-1586
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The development of cancer is associated with a number of risk factors, including smoking, obesity, sedentary lifestyles, alcohol consumption, infections, pollution, and dietary imbalances. Based on previous research, optimal consumption of fruits, vegetables, and whole grains, along with reduced consumption of red and processed meat, reduces cancer risk. According to this systematic review and meta-analysis, adherence to the Mediterranean diet is associated with lower cancer mortality and site-specific cancer development. A Mediterranean diet includes fruits, vegetables, nuts, legumes, fish, whole grains, extra virgin olive oil, and low amounts of red meat, processed meat, egg, and dairy, along with moderate amounts of red wine. According to this systematic review and meta-analysis, adherence to the Mediterranean diet reduces the risk of cancer mortality and the risk of developing cancers specific to the site, such as colorectal cancer, bladder cancer, gastric cancer, and lung cancer. Among the components of the Mediterranean diet, fruits, vegetables, and whole grains have been shown to reduce cancer risk. Bioactive substances found in Mediterranean diet components require additional robust studies to evaluate their benefits. A healthcare professional can use the results of this study to make clinical decisions and recommend therapeutic interventions to cancer patients.
Abstract
PURPOSE The aim of current systematic review was to update the body of evidence on associations between adherence to the Mediterranean diet (MedDiet) and risk of cancer mortality, site-specific cancer in the general population; all-cause, and cancer mortality as well as cancer reoccurrence among cancer survivors. METHODS A literature search for randomized controlled trials (RCTs), case-control and cohort studies published up to April 2020 was performed using PubMed and Scopus. Study-specific risk estimates for the highest versus lowest adherence to the MedDiet category were pooled using random-effects meta-analyses. Certainty of evidence from cohort studies and RCTs was evaluated using the NutriGrade scoring system. RESULTS The updated search revealed 44 studies not identified in the previous review. Altogether, 117 studies including 3,202,496 participants were enclosed for meta-analysis. The highest adherence to MedDiet was inversely associated with cancer mortality (RRcohort: 0.87, 95% CI 0.82, 0.92; N = 18 studies), all-cause mortality among cancer survivors (RRcohort: 0.75, 95% CI 0.66, 0.86; N = 8), breast (RRobservational: 0.94, 95% CI 0.90, 0.97; N = 23), colorectal (RRobservational: 0.83, 95% CI 0.76, 0.90; N = 17), head and neck (RRobservational: 0.56, 95% CI 0.44, 0.72; N = 9), respiratory (RRcohort: 0.84, 95% CI 0.76, 0.94; N = 5), gastric (RRobservational: 0.70, 95% CI 0.61, 0.80; N = 7), bladder (RRobservational: 0.87, 95% CI 0.76, 0.98; N = 4), and liver cancer (RRobservational: 0.64, 95% CI 0.54, 0.75; N = 4). Adhering to MedDiet did not modify risk of blood, esophageal, pancreatic and prostate cancer risk. CONCLUSION In conclusion, our results suggest that highest adherence to the MedDiet was related to lower risk of cancer mortality in the general population, and all-cause mortality among cancer survivors as well as colorectal, head and neck, respiratory, gastric, liver and bladder cancer risks. Moderate certainty of evidence from cohort studies suggest an inverse association for cancer mortality and colorectal cancer, but most of the comparisons were rated as low or very low certainty of evidence.
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Effects of Endurance Training Intensity on Pulmonary Diffusing Capacity at Rest and after Maximal Aerobic Exercise in Young Athletes.
Dridi, R, Dridi, N, Govindasamy, K, Gmada, N, Aouadi, R, Guénard, H, Laher, I, Saeidi, A, Suzuki, K, Hackney, AC, et al
International journal of environmental research and public health. 2021;18(23)
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Intermittent exercise, where small bouts of exercise are performed over a short period of time and endurance exercise, has been shown to be particularly effective at improving different aspects of lung function. This randomised control trial aimed to determine the effects of intense endurance training compared too moderate endurance training on lung function. The results showed that lung function was improved following intense endurance training but not moderate endurance training. It was concluded that training intensity may be the most important factor when increasing lung function in athletes. This study could be used by professionals to recommend intense endurance training to improve exercise capacity in athletes.
Abstract
This study compared the effects of varying aerobic training programs on pulmonary diffusing capacity (TLCO), pulmonary diffusing capacity for nitric oxide (TLNO), lung capillary blood volume (Vc) and alveolar-capillary membrane diffusing capacity (DM) of gases at rest and just after maximal exercise in young athletes. Sixteen healthy young runners (16-18 years) were randomly assigned to an intense endurance training program (IET, n = 8) or to a moderate endurance training program (MET, n = 8). The training volume was similar in IET and MET but with different work intensities, and each lasted for 8 weeks. Participants performed a maximal graded cycle bicycle ergometer test to measure maximal oxygen consumption (VO2max) and maximal aerobic power (MAP) before and after the training programs. Moreover, TLCO, TLNO and Vc were measured during a single breath maneuver. After eight weeks of training, all pulmonary parameters with the exception of alveolar volume (VA) and inspiratory volume (VI) (0.104 < p < 0889; 0.001 < ES < 0.091), measured at rest and at the end of maximal exercise, showed significant group × time interactions (p < 0.05, 0.2 < ES < 4.0). Post hoc analyses revealed significant pre-to-post decreases for maximal heart rates (p < 0.0001, ES = 3.1) and improvements for VO2max (p = 0.006, ES = 2.22) in the IET group. Moreover, post hoc analyses revealed significant pre-to-post improvements in the IET for DM, TLNO, TLCO and Vc (0.001 < p < 0.0022; 2.68 < ES < 6.45). In addition, there were increases in Vc at rest, VO2max, TLNO and DM in the IET but not in the MET participants after eight weeks of training with varying exercise intensities. Our findings suggest that the intensity of training may represent the most important factor in increasing pulmonary vascular function in young athletes.
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Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis.
Coggan, AR, Baranauskas, MN, Hinrichs, RJ, Liu, Z, Carter, SJ
Journal of the International Society of Sports Nutrition. 2021;18(1):66
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Previous reviews have concluded that dietary nitrate (NO3−) improves maximal neuromuscular power in humans, but these were based on a limited number of studies. This is the first systematic review and meta-analysis evaluating the effects of dietary NO3− supplementation on muscular power in humans. The study also aims to quantify the size of this beneficial effect. 19 studies with a total of 268 participants were included. Most of these used concentrated beetroot juice as the source of NO3− given as an acute dose (short term high level). A positive effect of dietary NO3− on muscle power was observed in all 19 studies. Analyses were done on sub groups - age, sex and the amount of muscle mass engaged in the activity. Dietary NO3− intake significantly increases maximal muscle power in humans. The magnitude of this effect has practical and clinical importance; not just for athletes but also for patient groups. This effect is independent of subject age, sex, or the amount of muscle mass engaged in the activity but may be greater with acute vs. repeated dosing. Further research is needed to determine factors such as the optimal supplementation regimen and target population.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This meta-analysis lends quantitative support to previous narrative reviews that nitrate supplementation can enhance maximal power output.
- These findings are highly relevant to team and strength sport athletes, who may not otherwise be supplementing with nitrates.
- These findings are also highly relevant for older populations, where risk of falls and fractures are high and can lead to significant adverse effects on health and quality of life.
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:
- In 2007, researchers uncovered the ingestion of dietary nitrates reduced the oxygen cost of submaximal exercise, and since, over 100 studies have examined the effects of nitrates on endurance performance.
- With regards to the impact of nitrates on maximal force output, only trivial results had been previously found.
- This review study found that while nitrates do not impact force development, they do demonstrate primary effect on the speed of muscle contraction (i.e. muscular power is the product of force x speed).
- The reviews primary finding was that nitrate intake can significantly enhance muscular power, regardless of subject age or sex.
Clinical practice applications:
- These new findings highlight the ability of dietary nitrates to improve neuromuscular power production is highly relevant for team sport athletes, due to the explosive nature of these sports with constant accelerations and decelerations during training and competition.
- In the general population, falls and fractures amongst older adults significantly reduces quality of life and costs the healthcare system hundreds of millions of pounds to treat.
- Improved contractile properties of muscle, most notably speed of contraction, may offer protection to older adults as well as the benefit of additional nitric oxide (NO) to support vascular health as well.
- The typical intake of dietary nitrates in the general population is about 31-185mg/day in Europe and 40-100mg/day in North America. Most studies use doses between 300-600mg of dietary nitrates. Increasing dietary or supplemental intake is key to achieving the neuromuscular effect.
Considerations for future research:
- The results of the present meta-analysis clearly demonstrate that dietary nitrates increases muscle power in humans, but the mechanism responsible for this effect is still unclear.
- There are notable differences between rodent and human metabolism of dietary nitrates, therefore the biochemical mechanism by which nitrate intake improves human muscle power requires additional study.
Abstract
BACKGROUND Previous narrative reviews have concluded that dietary nitrate (NO3-) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3- on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO3- supplementation on human muscle power. METHODS The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov , and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO3- on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors. RESULTS Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge's g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10- 11). There was limited heterogeneity between studies (i.e., I2 = 22.79%, H2 = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10- 9). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10- 12) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630). CONCLUSIONS Acute or chronic dietary NO3- intake significantly increases maximal muscle power in humans. The magnitude of this effect-on average, ~ 5%-is likely to be of considerable practical and clinical importance.