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The effects of prebiotics on gastrointestinal side effects of metformin in youth: A pilot randomized control trial in youth-onset type 2 diabetes.
Dixon, SA, Mishra, S, Dietsche, KB, Jain, S, Mabundo, L, Stagliano, M, Krenek, A, Courville, A, Yang, S, Turner, SA, et al
Frontiers in endocrinology. 2023;14:1125187
Abstract
DISCLOSURE SUMMARY Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose. BACKGROUND Metformin is the only approved first-line oral glucose lowering agent for youth with type 2 diabetes mellitus (Y-T2DM) but often causes gastrointestinal (GI) side effects, which may contribute to reduced treatment adherence and efficacy. Prebiotic intake may reduce metformin's side effects by shifting microbiota composition and activity. OBJECTIVE The aims of this study were to determine the feasibility and tolerability of a prebiotic supplement to improve metformin-induced GI symptoms and explore the changes in glycemia and shifts in the microbiota diversity. METHODS In a two-phase pilot clinical trial, we compared, stool frequency and stool form every 1-2 days, and composite lower GI symptoms (weekly) at initiation of daily metformin combined with either a daily prebiotic or a placebo shake in a 1-week randomized double-blind crossover design (Phase 1), followed by a 1-month open-labeled extension (Phase 2). Plasma glycemic markers and stool samples were collected before and after each phase. RESULTS Six Y-T2DM (17.2 ± 1.7y (mean ± SD), 67% male, BMI (42 ± 9 kg/m2), HbA1c (6.4 ± 0.6%)) completed the intervention. Stool frequency, stool composition, and GI symptom scores did not differ by group or study phase. There were no serious or severe adverse events reported, and no differences in metabolic or glycemic markers. After one week Phase 1metformin/placebo Proteobacteria, Enterobacteriaceae, and Enterobacteriales were identified as candidate biomarkers of metformin effects. Principle coordinate analyses of beta diversity suggested that the metformin/prebiotic intervention was associated with distinct shifts in the microbiome signatures at one week and one month. CONCLUSION Administration of a prebiotic fiber supplement during short-term metformin therapy was well tolerated in Y-T2DM and associated with modest shifts in microbial composition. This study provides a proof-of-concept for feasibility exploring prebiotic-metformin-microbiome interactions as a basis for adjunctive metformin therapy. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/, identifier NCT04209075.
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Prospective and Cross-sectional Associations of the Rectal Tissue Microbiome with Colorectal Adenoma Recurrence.
Byrd, DA, Vogtmann, E, Ortega-Villa, AM, Wan, Y, Gomez, M, Hogue, S, Warner, A, Zhu, B, Dagnall, C, Jones, K, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2023;32(3):435-443
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Abstract
BACKGROUND The gut microbiome is plausibly associated with colorectal cancer risk; however, previous studies mostly investigated this association cross-sectionally. We investigated cross-sectional and prospective associations of the rectal tissue microbiome with adenoma recurrence in the Polyp Prevention Trial (PPT). METHODS PPT is a 4-year randomized clinical trial of the effect of a dietary intervention on adenoma recurrence among community members. We extracted DNA from rectal biopsies at baseline, end of year 1, and end of year 4 among 455 individuals and sequenced the V4 region of the 16S rRNA gene. At each timepoint, we investigated associations of alpha diversity, beta diversity, and presence and relative abundance of select taxa with adenoma recurrence using multivariable logistic regression. RESULTS Variation in beta diversity was primarily explained by subject and minimally by year of collection or time between biopsy and colonoscopy. Cross-sectionally, year 4 alpha diversity was strongly, inversely associated with adenoma prevalence [ORQ3 vs. Q1 Shannon index = 0.40 (95% confidence interval, CI: 0.21-0.76)]. Prospective alpha diversity associations (i.e., baseline/year 1 alpha diversity with adenoma recurrence 3-4 years later) were weak or null, as were cross-sectional and prospective beta diversity-adenoma associations. Bacteroides abundance was more strongly, positively associated with adenoma prevalence cross-sectionally than prospectively. CONCLUSIONS Rectal tissue microbiome profiles may be associated with prevalent adenomas, with little evidence supporting prospective associations. IMPACT Additional prospective studies, with serial fecal and tissue samples, to explore microbiome-colorectal cancer associations are needed. Eventually, it may be possible to use microbiome characteristics as intervenable risk factors or screening tools.
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Probiotic for pathogen-specific Staphylococcus aureus decolonisation in Thailand: a phase 2, double-blind, randomised, placebo-controlled trial.
Piewngam, P, Khongthong, S, Roekngam, N, Theapparat, Y, Sunpaweravong, S, Faroongsarng, D, Otto, M
The Lancet. Microbe. 2023;4(2):e75-e83
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Staphylococcus aureus is a human pathogen that can cause several serious and often fatal infections. Treatment is complicated by widespread antibiotic resistance, such as in methicillin-resistant S aureus (MRSA). The aim of this study was to analyse whether a regimen of B subtilis (strain MB40) can decrease S aureus colonisation in humans and thereby overcome the problems related to topical decolonisation efforts and the use of antibiotics. This study was a single-centre, phase 2, double-blind, randomised, placebo-controlled trial. Individuals with S aureus colonisation were randomly assigned (1:1) to the intervention or control group. Results showed that colonisation densities in the intestine were reduced by probiotic treatment. Furthermore, there were no significant effects on the overall composition of the intestinal microbiome. Authors concluded that B subtilis probiotic could be used to reduce S aureus and MRSA colonisation prevalence and thus might have clinical potential to lower infection rates.
Abstract
BACKGROUND Decolonisation is considered a valuable means to reduce Staphylococcus aureus infection rates. However, previous topical strategies targeting the nose or skin had little success, and oral antibiotic-based decolonisation is ill advised because of eradication of the microbiota and development of antibiotic resistance. We previously showed that the probiotic Bacillus subtilis significantly diminished S aureus at the main intestinal colonisation site via specific bacterial interaction in mice; in this study, we tested this probiotic approach to control S aureus colonisation in humans. METHODS We did a single-centre, phase 2, double-blind, randomised, placebo-controlled trial in adults from the Songkhla region of Thailand who were colonised by S aureus. Eligible participants were adults (aged ≥18 years) without history of intestinal disease, antibiotic treatment, or hospital admission within the previous 90 days. Participants were excluded if they were pregnant, breastfeeding, taking probiotics, or had diarrhoea. Participants were allocated (1:1) to groups by computer randomisation in blocks of four, and research coordinators were masked to group allocation. Participants received 250 mg of probiotic B subtilis MB40 or placebo once per day for 30 days and S aureus colonisation was determined after the last dose was received. The primary outcome was colonisation by S aureus (continuous, mean decrease in colony-forming-unit count) in the intestine (by faecal counts) and nares (by nasal swabs) after intervention (30-day regimen of B subtilis probiotic). This trial is registered with the Thai Clinical Trials Registry, TCTR20210128003. FINDINGS The trial was done between Jan 29 and June 30, 2021, with enrolment taking place from Jan 29 to April 6, 2021. 115 participants were colonised by S aureus, either in the intestine (n=84), nose (n=50), or both (n=19), and were randomly assigned to treatment (n=55) and placebo groups (n=60). Oral probiotic B subtilis resulted in significant reduction of S aureus in stool (96·8%; p<0·0001) and nose (65·4%; p=0·0002). There were no differences in adverse effects or significant microbiome changes between the intervention and placebo groups. INTERPRETATION B subtilis probiotic eliminated more than 95% of the total S aureus colonising the human body without altering the microbiota. This probiotic strategy offers several key advantages over presently used decolonisation strategies for potential use in people with chronic or long-term risk of S aureus infection. Furthermore, by establishing a defining role of the intestinal colonisation site, our findings call for revisiting fundamental notions about S aureus colonisation. FUNDING National Research Council of Thailand and US National Institutes of Health.
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Association Between Plant and Animal Protein Intake and Overall and Cause-Specific Mortality.
Huang, J, Liao, LM, Weinstein, SJ, Sinha, R, Graubard, BI, Albanes, D
JAMA internal medicine. 2020;180(9):1173-1184
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High-quality protein diets have been shown in previous studies to have health benefits, mainly due to associated fat loss. However, studies examining dietary protein sources and death has not been extensively researched and is often controversial. This cohort study of 400,000 participants aimed to examine whether plant and animal protein intake from various sources effects death rates over 16 years. The results showed that increased intakes of plant protein were associated with lower rates of death by any cause in both men and women, whereas animal protein intake was not. Plant protein intake was associated with lower death rates from heart disease and stroke combined but did not affect death rates due to heart disease alone, cancer or respiratory disease. Interestingly when substituting 3% energy from animal protein to plant protein an association with lower death rates from all causes and heart disease was observed, which was especially apparent when substituting red meat and egg protein but not white meat protein. It was concluded that dietary modifications in favour of plant protein may incur health benefits resulting in longer life. This study could be used by healthcare professionals to understand that recommending dietary changes to increase plant protein intake may increase longevity.
Abstract
Importance: Although emphasis has recently been placed on the importance of high-protein diets to overall health, a comprehensive analysis of long-term cause-specific mortality in association with the intake of plant protein and animal protein has not been reported. Objective: To examine the associations between overall mortality and cause-specific mortality and plant protein intake. Design, Setting, and Participants: This prospective cohort study analyzed data from 416 104 men and women in the US National Institutes of Health-AARP Diet and Health Study from 1995 to 2011. Data were analyzed from October 2018 through April 2020. Exposures: Validated baseline food frequency questionnaire dietary information, including intake of plant protein and animal protein. Main Outcomes and Measures: Hazard ratios and 16-year absolute risk differences for overall mortality and cause-specific mortality. Results: The final analytic cohort included 237 036 men (57%) and 179 068 women. Their overall median (SD) ages were 62.2 (5.4) years for men and 62.0 (5.4) years for women. Based on 6 009 748 person-years of observation, 77 614 deaths (18.7%; 49 297 men and 28 317 women) were analyzed. Adjusting for several important clinical and other risk factors, greater dietary plant protein intake was associated with reduced overall mortality in both sexes (hazard ratio per 1 SD was 0.95 [95% CI, 0.94-0.97] for men and 0.95 [95% CI, 0.93-0.96] for women; adjusted absolute risk difference per 1 SD was -0.36% [95% CI, -0.48% to -0.25%] for men and -0.33% [95% CI, -0.48% to -0.21%] for women; hazard ratio per 10 g/1000 kcal was 0.88 [95% CI, 0.84-0.91] for men and 0.86 [95% CI, 0.82-0.90] for women; adjusted absolute risk difference per 10 g/1000 kcal was -0.95% [95% CI, -1.3% to -0.68%] for men and -0.86% [95% CI, -1.3% to -0.55%] for women; all P < .001). The association between plant protein intake and overall mortality was similar across the subgroups of smoking status, diabetes, fruit consumption, vitamin supplement use, and self-reported health status. Replacement of 3% energy from animal protein with plant protein was inversely associated with overall mortality (risk decreased 10% in both men and women) and cardiovascular disease mortality (11% lower risk in men and 12% lower risk in women). In particular, the lower overall mortality was attributable primarily to substitution of plant protein for egg protein (24% lower risk in men and 21% lower risk in women) and red meat protein (13% lower risk in men and 15% lower risk in women). Conclusions and Relevance: In this large prospective cohort, higher plant protein intake was associated with small reductions in risk of overall and cardiovascular disease mortality. Our findings provide evidence that dietary modification in choice of protein sources may influence health and longevity.
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Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors.
Merino, J, Jablonski, KA, Mercader, JM, Kahn, SE, Chen, L, Harden, M, Delahanty, LM, Araneta, MRG, Walford, GA, Jacobs, SBR, et al
Diabetes. 2020;69(1):112-120
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Individual risk of Coronary Artery Disease (CAD) and type 2 diabetes reflects the interplay between lifestyle behaviours acting on a backdrop of genetic predisposition. The aim of this study was to examine whether type 2 diabetes prevention strategies, either an intensive lifestyle intervention (ILS) or metformin treatment (MET), modify the association between CAD genetic risk and cardiometabolic risk factors (CRFs) in participants at high risk of type 2 diabetes. The study is a randomised controlled trial were participants were randomly allocated to one of the three groups; ILS (n = 1,079), MET (850 mg twice daily [n = 1,073]), or placebo (n = 1,082). Results indicate that there weren’t major significant differences in baseline characteristics, except for lower high-density lipoprotein and higher triglyceride in the placebo individuals compared with individuals assigned to MET or ILS. In fact, either an ILS or MET has a beneficial effect on 1-year change in different CRFs. Authors conclude that type 2 diabetes–preventive strategies for individuals at high risk of type 2 diabetes provide beneficial effects on CRFs regardless of CAD genetic risk profile.
Abstract
Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
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Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.
Hall, KD, Ayuketah, A, Brychta, R, Cai, H, Cassimatis, T, Chen, KY, Chung, ST, Costa, E, Courville, A, Darcey, V, et al
Cell metabolism. 2019;30(1):67-77.e3
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Diets high in ultra-processed foods have been related to several poor health outcomes and even death, possibly due to properties that make them highly palatable resulting in overeating and obesity. However, to date, there are few studies that demonstrate this relationship. This randomised control trial of 20 individuals aimed to compare the effects of an ultra-processed diet to an unprocessed diet on energy intake. The results showed that the ultra-processed diet resulted in higher energy intakes due to increased carbohydrates and fat, whereas energy intake during the unprocessed diet remained stable and this was not due to differences in pleasantness of familiarity. During the ultra-processed diet participants gained weight, and lost weight during the unprocessed phase, due to increased energy intake. It was concluded that eliminating ultra-processed foods from the diet decreases energy intake resulting in weight loss. Healthcare professionals could use this study to understand the importance of recommending a diet without ultra-processed foods to decrease overeating and improve health.
Abstract
We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean ± SE) 31.2 ± 1.6 years and BMI = 27 ± 1.5 kg/m2. Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508 ± 106 kcal/day; p = 0.0001), with increased consumption of carbohydrate (280 ± 54 kcal/day; p < 0.0001) and fat (230 ± 53 kcal/day; p = 0.0004), but not protein (-2 ± 12 kcal/day; p = 0.85). Weight changes were highly correlated with energy intake (r = 0.8, p < 0.0001), with participants gaining 0.9 ± 0.3 kg (p = 0.009) during the ultra-processed diet and losing 0.9 ± 0.3 kg (p = 0.007) during the unprocessed diet. Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.
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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
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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:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
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.
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.
Ferrucci, L, Fabbri, E
Nature reviews. Cardiology. 2018;15(9):505-522
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Inflammageing is a term used to describe elevated blood inflammatory markers that leads to frailty and increases an individual’s risk for heart disease, kidney disease and other physical and mental illnesses. Whether inflammageing is causal in heart disease is still uncertain. This large review of 310 papers aimed to understand the causes and role of inflammageing in heart disease and other illnesses associated with ageing. Causes of inflammageing were discussed and mechanisms are not fully understood. Genetic susceptibility, obesity, gut microbiota, gut permeability, when cells can no longer divide, and chronic infections were all implicated. The role of inflammageing in heart disease was a focus and the authors deduced that it was likely to be both causal and a result of heart disease. However, the administration of anti-inflammatories in heart disease has not always proved a successful treatment. Possible causes of inflammageing are likely to be linked and cumulative and although inflammation may cause age related diseases, its role in protecting the body means that its benefits outweigh its consequences. It was concluded that controlling inflammageing may prevent heart disease and other diseases associated with ageing. This study could be used by healthcare professionals to help understand what inflammageing is and its role in age related diseases.
Abstract
Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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A systematic review of attentional biases in disorders involving binge eating.
Stojek, M, Shank, LM, Vannucci, A, Bongiorno, DM, Nelson, EE, Waters, AJ, Engel, SG, Boutelle, KN, Pine, DS, Yanovski, JA, et al
Appetite. 2018;123:367-389
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Binge eating behaviour is a feature of certain eating disorders (such as binge eating disorder (BED), bulimia nervosa (BN) and binge-purge subtype of anorexia nervosa (AN). It can also be a problem for those who do not meet the criteria for an eating disorder diagnosis. The presence of binging, and a loss of control is a risk for eating disorder development, psychological distress and/or excess body weight. It is important to explore the factors that may cause or maintain binge eating behaviour. Attentional bias (AB; paying attention to some things and ignoring others) is thought to contribute to the development of eating disorders when it is maladaptive. This systematic review of 50 cross-sectional designed articles explores findings on AB to food cues, weight and shape cues and threatening cues. The review found that people with binge eating behaviour may be oversensitive to the rewarding properties of food and have increased AB for weight/shape cues, suggesting it needs to be considered when supporting people who binge. Longitudinal research is needed to explore if AB is a factor in the development of eating disorders and binge eating.
Abstract
OBJECTIVE Attentional bias (AB) may be one mechanism contributing to the development and/or maintenance of disordered eating. AB has traditionally been measured using reaction time in response to a stimulus. Novel methods for AB measurement include eye tracking to measure visual fixation on a stimulus, and electroencephalography to measure brain activation in response to a stimulus. This systematic review summarizes, critiques, and integrates data on AB gathered using the above-mentioned methods in those with binge eating behaviors, including binge eating, loss of control eating, and bulimia nervosa. METHOD Literature searches on PubMed and PsycInfo were conducted using combinations of terms related to binge eating and biobehavioral AB paradigms. Studies using AB paradigms with three categories of stimuli were included: food, weight/shape, and threat. For studies reporting means and standard deviations of group bias scores, Hedges' g effect sizes for group differences in AB were calculated. RESULTS Fifty articles met inclusion criteria and were reviewed. Individuals who binge eat in the absence of compensatory behaviors show an increased AB to food cues, but few studies have examined such individuals' AB toward weight/shape and threatening stimuli. Individuals with bulimia nervosa consistently show an increased AB to shape/weight cues and socially threatening stimuli, but findings for AB to food cues are mixed. DISCUSSION While there are important research gaps, preliminary evidence suggests that the combination of AB to disorder-specific cues (i.e., food and weight/shape) and AB toward threat may be a potent contributor to binge eating. This conclusion underscores previous findings on the interaction between negative affect and AB to disorder-specific cues. Recommendations for future research are provided.
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Emollient use alters skin barrier and microbes in infants at risk for developing atopic dermatitis.
Glatz, M, Jo, JH, Kennedy, EA, Polley, EC, Segre, JA, Simpson, EL, Kong, HH
PloS one. 2018;13(2):e0192443
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Atopic dermatitis (AD) is a type of eczema common in babies and young children. Poor function of the skin barrier is thought to lead to changes in the composition of bacteria found on the skin. This small study investigated the effects of daily use of an emollient, Cetaphil Moisturising Cream, on the barrier function and bacterial communities on the skin of infants at risk of developing AD. After 6 months, the emollient group had a lower skin pH than the control group. The group using the emollient had more diverse skin bacterial communities than the control group. The proportion of Streptococcus salivarius was higher in the emollient versus control groups. The authors concluded that lower skin pH and increased skin bacterial diversity after long-term emollient use may reduce inflammation and lower the risk of infants developing AD.
Abstract
BACKGROUND Emollients are a mainstay of treatment in atopic dermatitis (AD), a disease distinguished by skin bacterial dysbiosis. However, changes in skin microbiota when emollients are used as a potential AD preventative measure in infants remain incompletely characterized. RESULTS We compared skin barrier parameters, AD development, and bacterial 16S ribosomal RNA gene sequences of cheek, dorsal and volar forearm samples from 6-month-old infants with a family history of atopy randomized to receive emollients (n = 11) or no emollients (controls, n = 12). The emollient group had a lower skin pH than the control group. The number of bacterial taxa in the emollient group was higher than in the control group at all sites. The Streptococcus salivarius proportion was higher in the emollient versus control groups at all sites. S. salivarius proportion appeared higher in infants without AD compared to infants with AD. A decrease in S. salivarius abundance was further identified in a separate larger population of older children demonstrating an inverse correlation between AD severity at sampling sites and S. salivarius proportions. CONCLUSIONS The decreased skin pH and the increased proportion of S. salivarius after long-term emollient use in infants at risk for developing AD may contribute to the preventative effects of emollients in high-risk infants.