-
1.
Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.
Elhassan, YS, Kluckova, K, Fletcher, RS, Schmidt, MS, Garten, A, Doig, CL, Cartwright, DM, Oakey, L, Burley, CV, Jenkinson, N, et al
Cell reports. 2019;28(7):1717-1728.e6
-
-
-
Free full text
Plain language summary
As the body ages, there is a decline in muscle mass and function, which can be combatted with diet, exercise, and supplementation. Nicotinamide riboside (NR) or vitamin B3 has been shown in animal studies to promote healthy muscle, however its effects in human muscle are unknown. This randomised control trial of overweight older men aimed to determine if NR can be used by muscle and whether it has any effect on muscle function. The results showed that NR supplementation (1 g/day) for 3 weeks can be used by the muscle but had no effect on muscle function as shown by the hand grip test. Supplementation also decreased energy production in muscle and had anti-inflammatory effects. It was concluded that NR is available to muscle and that it may have anti-inflammatory properties, which may be of benefit to older individuals.
Abstract
Nicotinamide adenine dinucleotide (NAD+) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR.
-
2.
Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.
Stekovic, S, Hofer, SJ, Tripolt, N, Aon, MA, Royer, P, Pein, L, Stadler, JT, Pendl, T, Prietl, B, Url, J, et al
Cell metabolism. 2019;30(3):462-476.e6
-
-
-
-
Free full text
Plain language summary
Intermittent fasting and calorie restriction are believed to reduce cardiometabolic risk factors and increase longevity. Fasting alternate days (ADF) involves fasting for 36 hours and eating ad libitum for 12 hours. Thirty healthy participants were randomly assigned to a long-term ADF intervention group for ≥6 months against sixty participants in the control group. After completing the cross-sectional study arm, sixty healthy participants in the control group were randomly assigned to either a four-week short-term ADF intervention group or a control group with an ad libitum diet. Study participants adhered well to the fasting regimen. Both short-term and long-term ADF intervention groups showed a significant reduction in calorie intake, improvements in anthropometric and cardiovascular parameters including reduced BMI, substantial reduction in trunk fat, lower heart rate, increased serum β-hydroxybutyrate which is cardioprotective and anti-ageing, reduced circulating triiodothyronine (fT3) levels which indicate longevity. Short-term ADF reduced systolic and diastolic pressure, mean arterial pressure, pulse pressure, and pulse wave velocity. Long-term ADF intervention reduced circulating total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides, the age-related biomarker sICAM-1 for disease and inflammation, and improved lipid and amino acid metabolites. ADF did not affect insulin sensitivity. Although red blood cells and iron levels were altered, ADF interventions were not associated with iron deficiency. Healthcare professionals can use the results of this study to understand the cardioprotective and anti-ageing properties of ADF. However, further long-term robust studies are required to evaluate the effect of long-term ADF on bone health.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short duration (<4 weeks) alternate day fasting may be an effective way to implement caloric restriction, improve body composition and reduce cardiovascular disease risk in healthy non-overweight adults.
- >6 months alternate fasting does not appear to be associated with reduced bone mass, bone mineral density of the lumbar spine region, white blood cell counts, ferritin and transferrin when compared to healthy controls.
- Both short term and long term alternate day fasting may reduce triiodothyronine in healthy adults. Low levels of fT3 without thyroid gland dysfunction has been associated with longevity in humans.
- Alternate day fasting should be performed alongside a trained clinician to reduce the risk of adverse effects due to critical medical conditions.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
Animal models have consistently demonstrated the healthspan and lifespan benefits of caloric restriction. However, chronic caloric restriction in humans has proven difficult to maintain.
Intermittent fasting may serve as a more manageable alternative to continuous caloric restriction. This randomised controlled trial and cross sectional analysis aimed to investigate the effects of alternate day fasting (ADF) on heart rate, blood pressure, cholesterol levels, CVD risk, body composition, and the metabolome and proteome of healthy, non-overweight adults (cohort median age between 48 and 52 years).
Methods
Prior to the enrollment of the study a cross sectional analysis was conducted on healthy adults engaged in long term (>6 months) alternate day fasting (n=30) and a control group (n=60).
The 60 participants from the cross sectional analysis control group were then randomised to either a 4 week ADF group or a control group. In both the >6 months and 4 weeks of ADF groups, participants were instructed to eat every second-day ad libitum, but to completely exclude solid and liquid foods and caloric beverages on fasting days.
Results
The cross sectional analysis identified that the alternate day fasting group:
- Consumed fewer calories vs the control group (−28.56%, p=0.0002).
- Had lower levels of circulating total cholesterol (p=0.004), LDL (p=0.011), VLDL (p=0.009), triglycerides (p=0.010) and a lower heart rate (p=0.040) vs the control group.
- Lower levels of soluble intercellular adhesion molecule-1 (sICAM-1) (p value 0.048), an age-associated inflammatory marker.
- Reduced circulating triiodothyronine (p<0.001) compared to the control group.
- In the metabolome, 54 out of 113 detected significantly modified metabolites (p value < 0.05) were at least 20% higher after 36 h of fasting, of which the majority (>95%) were lipids or free fatty acids, including polyunsaturated free fatty acids (PUFAs), α-tocopherol, and a type of vitamin E. 49 metabolites were at least 20% lower, consisting mainly (44.9%) of amino acids or related metabolites. Low levels of circulating amino acids have been found to increase lifespan in model organisms. The authors concluded that the elevation in fatty acids may be due to increased lipolysis from adipose tissue while the reduction in amino acids may be the result of increased gluconeogenesis.
- 13 out of 2,089 significantly (p value < 0.05) modulated protein hits within the PBMC proteome showed an increase of ≥15%, while the remaining proteins were downregulated after 36 h of fasting. Gene set enrichment analysis (GSEA) performed on the PBMC proteome unveiled changes in pathways related to lipid metabolism, pathways related to energy metabolism and stress response.
Following the 4 week intervention the alternate day fasting group demonstrated:
- Reduced caloric intake from baseline vs. the control group (−37.40% vs. −8.22%, p=0.0012).
- Greater reductions in body weight (−3.5kg vs −0.2kg, p<0.0001), BMI (−1.23kg/m2 vs −0.02kg/m2, p<0.0001) and improvements in their fat to lean mass ratio (−6.3% ± 5.0 percentage points, p value < 0.0001).
- Reduced systolic (−4.5mmHg, p=0.006) and diastolic (−2.5mmHg, p=0.03) blood pressure, heart rate (-4.5 b/min, p=0.0019), arterial (−3mmHg, p=0.0087) and pulse pressure (−2.5mmHg, p=0.0088) as well as pulse wave velocity (−1.538%, p=0.0362). Pulse wave velocity measures the rate at which pressure moves down the vessel wall and is a measure of arterial stiffness.
- Reduced circulating triiodothyronine (p<0.001) from baseline values.
Clinical practice applications:
The cross sectional analysis did not identify any differences in the long-term (>6 months) alternate day fasting group and control group in bone mass, bone mineral density of the lumbar spine region, white blood cell counts, ferritin and transferrin when compared to healthy controls. RBC counts and iron metabolism markers in the blood plasma (hematocrit, haemoglobin, iron, and transferrin saturation), were lower in the >6 months of ADF group but stayed within the reference range.
The randomised controlled trial demonstrated that alternate day fasting may be an effective intervention to reduce caloric intake, improve body composition and reduce cardiovascular disease risk in healthy non-overweight adults within 4 weeks.
Compliance rate was high with only 1 drop out in the alternate day fasting group of the randomised controlled trial.
Both the 4 week intervention and long-term (>6 month) analysis identified a reduction in triiodothyronine amongst the ADF groups. Low levels of triiodothyronine in absence of thyroid gland dysfunction has been associated with longevity in humans.
Considerations for future research:
- Future larger studies in non-healthy and/or overweight/obese populations would be useful to determine safety and efficacy of alternate day fasting within that population group.
- Further studies comparing alternate day fasting with continuous caloric restriction would be useful to identify which intervention is most beneficial for body composition and cardioprotection.
- Subgroup analysis of diet composition and diet quality may help to identify the most appropriate/inappropriate diet to compliment alternate day fasting.
- Longer duration randomised controlled trials are needed to identify any health risks or deficiencies which may develop with long term caloric restriction and alternate day fasting.
Abstract
Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
-
3.
Combined aerobic exercise and high-intensity respiratory muscle training in patients surgically treated for non-small cell lung cancer: a pilot randomized clinical trial.
Messaggi-Sartor, M, Marco, E, Martínez-Téllez, E, Rodriguez-Fuster, A, Palomares, C, Chiarella, S, Muniesa, JM, Orozco-Levi, M, Barreiro, E, Güell, MR
European journal of physical and rehabilitation medicine. 2019;55(1):113-122
-
-
-
Free full text
Plain language summary
Lung cancer treatment initiates a deconditioning storm that further reduces the capacity to deliver and utilize oxygen and metabolic substrates during exercise, contributing to poor cardiorespiratory fitness. The main aim of this study was to assess the impact of aerobic exercise with inspiratory and expiratory muscle training on cardiovascular fitness and respiratory muscle dysfunction in non-small cell lung cancer patients. The study is a two-centre, prospective, single-blind, pilot randomized controlled trial. The eligible patients were randomly assigned to the exercise (n=16) or control groups (n=21). Study results showed strong improvement in respiratory muscle strength and exercise capacity following high-intensity inspiratory and expiratory muscle training. Authors conclude that structured and supervised exercise interventions should be recommended to patients with lung cancer.
Abstract
BACKGROUND Lung resection surgery further decreases exercise capacity and negatively affects respiratory muscle function in patients with non-small cell lung cancer (NSCLC). The best design for exercise interventions in these patients has not been determined yet. AIM: To assess the impact of aerobic exercise and high-intensity respiratory muscle training on patient outcomes following lung cancer resection surgery. DESIGN Prospective, single-blind, pilot randomized controlled trial. SETTING Outpatient cardiopulmonary rehabilitation unit of two university hospitals. POPULATION Thirty-seven patients with NSCLC after tumor resection. METHODS Patients were randomly assigned to exercise training or usual post-operative care. The training program consisted of aerobic exercises and high-intensity respiratory muscle training (24 supervised sessions, 3 per week, 8 weeks). Primary outcome was exercise capacity assessed with peak oxygen uptake (VO2peak) during cardiopulmonary exercise test. Secondary outcomes included changes in respiratory muscle strength, levels of serum insulin growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and quality of life assessed with the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) questionnaire. RESULTS The 8-week training program was associated with significant improvement in VO2peak (2.13 mL/Kg/min [95%CI 0.06 to 4.20]), maximal inspiratory and expiratory pressures (18.96 cmH2O [95% CI 2.7 to 24.1] and 18.58 cmH2O [95% CI 4.0 to 33.1], respectively) and IGFBP-3 (0.61 µg/mL [%95 CI 0.1 to 1.12]). No significant differences were observed in the EORTC QLQ-C30. CONCLUSIONS An 8-week exercise program consisting of aerobic exercise and high-intensity respiratory muscle training improved exercise capacity, respiratory muscle strength, and serum IGFBP-3 levels in NSCLC patients after lung resection. There was no impact on the other outcomes assessed. CLINICAL REHABILITATION IMPACT A combination of aerobic exercise and respiratory muscle training could be included in the rehabilitation program of deconditioned patients with NSCLC after lung resection surgery.
-
4.
The Effect of Vitamin B12 and Folic Acid Supplementation on Serum Homocysteine, Anemia Status and Quality of Life of Patients with Multiple Sclerosis.
Nozari, E, Ghavamzadeh, S, Razazian, N
Clinical nutrition research. 2019;8(1):36-45
-
-
-
Free full text
Plain language summary
Multiple sclerosis (MS) is a relatively common chronic neurological disorder in which damage to the protective covering of neurons occurs in different areas of the central nervous system. Relapsing remitting multiple sclerosis (RRMS) is the relapsing episodes of MS and periods of stability in between relapses. The aim of this study was to determine the effect of vitamin B12 and folic acid supplementation on serum homocysteine (amino acid), anaemia status and quality of life of RRMS patients The study is a double-blind clinical trial which recruited 50 participants. The participants were randomly assigned to one of the 2 groups of RRMS: the vitamin group or the placebo group. Results indicate that increasing the consumption of folic acid and vitamin B12 improved physical and mental dimensions of quality of life in the vitamin group. However, in the placebo group, improvements were only limited to the psychological dimension of quality of life and no significant change in the physical dimension was observed. Authors conclude that homocysteine levels, anaemia status, and eventually quality of life of patients with MS can be significantly improved by administration of 1mg of vitamin B12 monthly and adding rich-food sources of folic acid on their diet.
Abstract
Plasma homocysteine level and megaloblastic anemia status are two factors that can affect the quality of life of patients with multiple sclerosis (MS). We conducted this study to determine the effect of vitamin B12 and folic acid supplementation on serum homocysteine, megaloblastic anemia status and quality of life of patients with MS. A total of 50 patients with relapsing remitting multiple sclerosis (RRMS) included in this study which divided into 2 groups. The vitamin group received 5 mg folic acid tablet daily and 3 doses of vitamin B12 (1,000 mcg) injection and the other group received placebo and normal saline injection (same doses). The quality of life was measured by using Multiple Sclerosis Quality of Life-54 questionnaire (MSQOL-54). Fully automated fluorescence polarization immunoassay was used to measure serum homocysteine, vitamin B12 and folate. Complete blood count blood test was conducted to determine the anemia status. The mean homocysteine level reduced by 2.49 ± 0.39 µmol/L (p = 0.001), hemoglobin increased from 11.24 ± 1.54 to 13.12 ± 1.05 g/dL (p = 0.001), and mean corpuscular volume decreased from 95.50 ± 6.65 to 89.64 ± 4.24 in the vitamin group (p = 0.001). There was a significant improvement in the mental field of life quality in the placebo group (37.46 ± 19.01 to 50.98 ± 21.64; p = 0.001), whereas both physical and mental fields of quality of life were improved significantly in the vitamin group (40.38 ± 15.07 to 59.21 ± 12.32 and 29.58 ± 15.99 to 51.68 ± 18.22, respectively; p = 0.001). Serum homocysteine level decrease and anemia status improvement with vitamin B12 and folic acid supplementation reveal the potential role of these two vitamins in improving the life quality of MS patients. TRIAL REGISTRATION Iranian Registry of Clinical Trials Identifier: IRCT2015100313678N7.
-
5.
Effect of Lactobacillus plantarum TWK10 on Exercise Physiological Adaptation, Performance, and Body Composition in Healthy Humans.
Huang, WC, Lee, MC, Lee, CC, Ng, KS, Hsu, YJ, Tsai, TY, Young, SL, Lin, JS, Huang, CC
Nutrients. 2019;11(11)
-
-
-
Free full text
Plain language summary
Probiotics are widely used for health promotion. This study specifically looks at one strain of Lactobacillus plantarum TWK10 and its effects on physiology and body composition in 54 healthy participants (50/50 men and women), aged 20-30 years, none of which were professional athletes. The double-blind placebo-controlled experiment divided the participants into groups of placebo, low dose probiotics and high dose probiotics to determine the effects of probiotics on exercise performance over a 6 week period. During this time the participants were required to carry out a series of treadmill exercises and biometric exams including monitoring heart rate, oxygen consumption, body mass, and fatigue parameters measured in blood work (serum lactate, ammonia, glucose, creatine kinase, aspartate transaminase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and uric acid) for physiological adaption. The results showed that the probiotics elevated exercise performance and improved fatigue in a dose-dependent manner. They observed that muscle mass increased and fat mass decreased in the treatment groups compared to the placebo. As such they conclude that Lactobacillus plantarum TWK10 has beneficial physiological effects to improve aerobic performance.
Abstract
Probiotics have been rapidly developed for health promotion, but clinical validation of the effects on exercise physiology has been limited. In a previous study, Lactobacillus plantarum TWK10 (TWK10), isolated from Taiwanese pickled cabbage as a probiotic, was demonstrated to improve exercise performance in an animal model. Thus, in the current study, we attempted to further validate the physiological function and benefits through clinical trials for the purpose of translational research. The study was designed as a double-blind placebo-controlled experiment. A total of 54 healthy participants (27 men and 27 women) aged 20-30 years without professional athletic training were enrolled and randomly allocated to the placebo, low (3 × 1010 colony forming units (CFU)), and high dose (9 × 1010 CFU) TWK10 administration groups (n = 18 per group, with equal sexes). The functional and physiological assessments were conducted by exhaustive treadmill exercise measurements (85% VO2max), and related biochemical indices were measured before and after six weeks of administration. Fatigue-associated indices, including lactic acid, blood ammonia, blood glucose, and creatinine kinase, were continuously monitored during 30 min of exercise and a 90 min rest period using fixed intensity exercise challenges (60% VO2max) to understand the physiological adaptation. The systemic inflammation and body compositions were also acquired and analyzed during the experimental process. The results showed that TWK10 significantly elevated the exercise performance in a dose-dependent manner and improved the fatigue-associated features correlated with better physiological adaptation. The change in body composition shifted in the healthy direction for TWK10 administration groups, especially for the high TWK10 dose group, which showed that body fat significantly decreased and muscle mass significantly increased. Taken together, our results suggest that TWK10 has the potential to be an ergogenic aid to improve aerobic endurance performance via physiological adaptation effects.
-
6.
The Fluid Aspect of the Mediterranean Diet in the Prevention and Management of Cardiovascular Disease and Diabetes: The Role of Polyphenol Content in Moderate Consumption of Wine and Olive Oil.
Ditano-Vázquez, P, Torres-Peña, JD, Galeano-Valle, F, Pérez-Caballero, AI, Demelo-Rodríguez, P, Lopez-Miranda, J, Katsiki, N, Delgado-Lista, J, Alvarez-Sala-Walther, LA
Nutrients. 2019;11(11)
-
-
-
Free full text
Plain language summary
The Mediterranean diet is considered one of the most studied diets in scientific literature and this review specifically looks at two fluid aspects of the MedDiet; olive oil and red wine. Olive oil is rich in phenolic compounds and red wine in polyphenols and the study looks at their therapeutic effect on cardiovascular disease prevention, particularly on lipids, blood pressure, plaque and glucose metabolism. Known mechanisms of the MedDiet include reduction of inflammatory and oxidative stress markers, and an improvement in lipid profile and insulin sensitivity. Polyphenols are important antioxidants abundant in plant foods including olives and red grapes used in wine (known to be x10 richer in polyphenols than white wine). The review reports that low to moderate consumption of red wine 30-50g daily lowers risk factors for CVD, improve HDL lipid profile, exerts a beneficial effect on blood pressure (BP), promotes vasodilation thus helping to reduce plaques and finally limited data shows it may beneficially affect insulin resistance. Polyphenols in olives were reported to reduce blood pressure, reduce LDL lipids and increase HDL lipids, support weight loss and help prevent obesity, metabolic syndrome and type II diabetes, reduce inflammation and oxidative stress, and possibility benefit gut microbiota. The review concludes that both fluids exert cardio-protection when consumed in moderation as part of a MedDiet.
Abstract
A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.
-
7.
Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis.
Uusitupa, M, Khan, TA, Viguiliouk, E, Kahleova, H, Rivellese, AA, Hermansen, K, Pfeiffer, A, Thanopoulou, A, Salas-Salvadó, J, Schwab, U, et al
Nutrients. 2019;11(11)
-
-
-
Free full text
Plain language summary
With Type 2 Diabetes growing globally this paper analyses whether T2D is preventable with lifestyle measures including diet. Seven RCTs were included for review with a total of 4090 participants, and 2466 incidents of T2D, and were chosen on the basis that the lifestyle interventions included both physical exercise and diet (typically Mediterranean Diet). They found that diet and lifestyle intervention reduced the risk of T2D by 47%. Sustained risk reduction was also found in follow-up studies up to 10 years later with participants maintaining improved blood glucose control. Lifestyle interventions may also reduce risk factors for cardiovascular disease. Weight reduction was considered a cornerstone of preventing T2D and adherence to lifestyle changes a key element in long term prevention. Dietary foods reviewed include processed meats, white rice and sugars which correlated highly with T2D whilst leafy greens, berries, wholegrains, legumes, dietary fibre and yoghurt correlate with a lower risk of T2D. Dietary patterns of skipping breakfast and snacking correlate higher with T2D. Different criteria for evaluating physical activity estimate that it reduces risk factors by 50%. In conclusion there is high evidence that lifestyle factors which optimise diet, increase physical activity and promote weight reduction are preventative factors for T2D and can be sustained long term.
Abstract
Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications.
-
8.
Effect of High-Dose Marine Omega-3 Fatty Acids on Atherosclerosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Sekikawa, A, Cui, C, Sugiyama, D, Fabio, A, Harris, WS, Zhang, X
Nutrients. 2019;11(11)
-
-
-
Free full text
Plain language summary
This systematic review and meta-analysis reports that high dose omega 3 at a dose of 3g/day with 90% purity significantly slowed the progression of atherosclerosis and is a promising mechanism for reducing cardiovascular (CVD) incidents. The study reviewed 6 articles from 2016-2017 with a total of 693 participants, which met the criteria of omega 3 and a primary outcome on atherosclerosis. Only one trial was placebo controlled with the remaining five open-label trials with no placebo. Four of the trials were conducted in Japan using a highly purified EPA whilst the remaining trials used an EPA / DHA combination. The effect of high dose omega 3 was significant even after removing the two most influential studies. Preclinical studies in animal models show that Omega 3 slows atherosclerosis progression through various molecular mechanisms. In humans there is less conclusive evidence and observational studies report that dietary intake of Omega 3 has no significant correlation with coronary artery calcification, the measure used to assess atherosclerosis. The limitation of this study is that different technologies were used to assess atherosclerosis across the selected trials. However, the authors conclude that the anti-atherosclerotic properties of high-dose OM3 are one potential mechanism in reducing CVD risk.
Abstract
A recent randomized controlled trial (RCT), the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), reported that high-dose marine omega-3 fatty acids (OM3) significantly reduce cardiovascular disease (CVD) outcomes, yet the mechanisms responsible for this benefit remain unknown. To test the hypothesis that high-dose OM3 is anti-atherosclerotic, we performed a systematic review and meta-analysis of RCT of high-dose OM3 on atherosclerosis. The protocol of this systematic review was registered with PROSPERO (CRD42019125566). PubMed, Embase, Cochran Central Register for Controlled Trials, and Clinicaltrials.gov databases were searched using the following criteria: adult participants, high-dose OM3 (defined as ≥3.0 g/day, or in Japan 1.8 g/day and purity ≥90%) as the intervention, changes in atherosclerosis as the outcome, and RCTs with an intervention duration of ≥6 months. A random-effects meta-analysis was used to pool estimates across studies. Among the 598 articles retrieved, six articles met our criteria. Four RCTs evaluated atherosclerosis in the coronary and two in the carotid arteries. High-dose OM3 significantly slowed the progression of atherosclerosis (standardized mean difference -1.97, 95% confidence interval -3.01, -0.94, p < 0.001). The results indicate that anti-atherosclerotic effect of high-dose OM3 is one potential mechanism in reducing CVD outcomes demonstrated in the REDUCE-IT trial.
-
9.
A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee.
Majeed, M, Majeed, S, Narayanan, NK, Nagabhushanam, K
Phytotherapy research : PTR. 2019;33(5):1457-1468
-
-
-
Free full text
-
Plain language summary
Osteoarthritis (OA) is an age-related, degenerative joint disorder which affects many people worldwide. It causes pain, most frequently in the large joints such as knee and hips and is characterised by pain, decreased mobility and negative effects on the quality of life. This randomised, double-blind placebo controlled trial of 48 adults between the age of 35 and 75, aimed to evaluate the safety and efficacy of Boswellia serrata extract on newly diagnosed or untreated patients with OA of the knee. 340mg of Boswellia serrata extract was administered daily in 2 doses to the treatment group for 120 days. Outcome measures were WOMAC scores on pain, stiffness and physical function; a 6 min walk test assessing distance; physician assessment of range of motion, strength, stability and tenderness; x-ray images of joint space and growths; and hs-CRP, a blood marker of inflammation. The researchers found that the treatment group significantly improved, with reduced pain and stiffness compared to placebo. X-ray assessment also showed significantly improved knee join space and reductions in abnormal bone spur growth in the treatment group. Additionally, the treatment group had significantly lower hs-CRP compared to placebo. No adverse effects were reported. Whilst this is a small trial, Nutrition Practitioners working with patients with OA could consider the use of Boswellia serrata extract in their supplement protocols.
Abstract
A double-blind, placebo-controlled human trial was conducted to evaluate the safety and efficacy of a standardized oral supplementation of Boswellin®, a novel extract of Boswellia serrata extract (BSE) containing 3-acetyl-11-keto-β-boswellic acid (AKBBA) with β-boswellic acid (BBA). A total of 48 patients with osteoarthritis (OA) of the knee were randomized and allocated to the BSE and placebo groups for intervention. Patients were administered BSE or placebo for a period of 120 days. The trial results revealed that BSE treatment significantly improved the physical function of the patients by reducing pain and stiffness compared with placebo. Radiographic assessments showed improved knee joint gap and reduced osteophytes (spur) confirming the efficacy of BSE treatment. BSE also significantly reduced the serum levels of high-sensitive C-reactive protein, a potential inflammatory marker associated with OA of the knee. No serious adverse events were reported. This is the first study with BSE conducted for a period of 120 days, longer than any other previous clinical trial on patients with OA of the knee. The findings provide evidence that biologically active constituents of BSE, namely, AKBBA and BBA, act synergistically to exert anti-inflammatory/anti-arthritic activity showing improvement in physical and functional ability and reducing the pain and stiffness.
-
10.
Additional Effects of Nutritional Antioxidant Supplementation on Peripheral Muscle during Pulmonary Rehabilitation in COPD Patients: A Randomized Controlled Trial.
Gouzi, F, Maury, J, Héraud, N, Molinari, N, Bertet, H, Ayoub, B, Blaquière, M, Bughin, F, De Rigal, P, Poulain, M, et al
Oxidative medicine and cellular longevity. 2019;2019:5496346
-
-
-
Free full text
Plain language summary
Chronic obstructive pulmonary disease (COPD) is systematically associated with comorbidities. Muscle atrophy and weakness are therefore targets of exercise training interventions in pulmonary rehabilitation (PR). The aim of the study was to test the effects of oral antioxidant supplementation with vitamins and trace elements (i.e. vitamins C and E, zinc and selenium) versus placebo on muscle endurance (primary outcome) and muscle strength, oxidative stress, inflammation, and PR outcomes (secondary outcomes). The study is a randomized double-blind controlled trial during PR. COPD patients (aged between 40 and 78 years) were randomly assigned to the PR antioxidant group or to the PR placebo group. Results indicate that nutritional antioxidant supplementation (vitamins C and E, zinc, and selenium) failed to further improve the patients’ quadriceps endurance. However, results also demonstrate that additional improvements of three secondary outcomes and a trend toward increased muscle type I fiber proportion with supplementation versus placebo during PR. Authors conclude that efficient antioxidant supplementation results in greater improvement in muscle function when compared to placebo in combination with exercise training.
Abstract
BACKGROUND Skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) is not fully reversed by exercise training. Antioxidants are critical for muscle homeostasis and adaptation to training. However, COPD patients experience antioxidant deficits that worsen after training and might impact their muscle response to training. Nutritional antioxidant supplementation in combination with pulmonary rehabilitation (PR) would further improve muscle function, oxidative stress, and PR outcomes in COPD patients. METHODS Sixty-four COPD patients admitted to inpatient PR were randomized to receive 28 days of oral antioxidant supplementation targeting the previously observed deficits (PR antioxidant group; α-tocopherol: 30 mg/day, ascorbate: 180 mg/day, zinc gluconate: 15 mg/day, selenomethionine: 50 μg/day) or placebo (PR placebo group). PR consisted of 24 sessions of moderate-intensity exercise training. Changes in muscle endurance (primary outcome), oxidative stress, and PR outcomes were assessed. RESULTS Eighty-one percent of the patients (FEV1 = 58.9 ± 20.0%pred) showed at least one nutritional antioxidant deficit. Training improved muscle endurance in the PR placebo group (+37.4 ± 45.1%, p < 0.001), without additional increase in the PR antioxidant group (-6.6 ± 11.3%; p = 0.56). Nevertheless, supplementation increased the α-tocopherol/γ-tocopherol ratio and selenium (+58 ± 20%, p < 0.001, and +16 ± 5%, p < 0.01, respectively), muscle strength (+11 ± 3%, p < 0.001), and serum total proteins (+7 ± 2%, p < 0.001), and it tended to increase the type I fiber proportion (+32 ± 17%, p = 0.07). The prevalence of muscle weakness decreased in the PR antioxidant group only, from 30.0 to 10.7% (p < 0.05). CONCLUSIONS While the primary outcome was not significantly improved, COPD patients demonstrate significant improvements of secondary outcomes (muscle strength and other training-refractory outcomes), suggesting a potential "add-on" effect of the nutritional antioxidant supplementation (vitamins C and E, zinc, and selenium) during PR. This trial is registered with NCT01942889.