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Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary.
Richman, S, Morris, MC, Broderick, G, Craddock, TJA, Klimas, NG, Fletcher, MA
Clinical therapeutics. 2019;41(5):798-805
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Myalgic encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/ CFS), is a disease characterized by an inability to exert oneself physically, often coupled with a combination of other symptoms, including sleep disorders, severe unpredictable pain, and compromised cognitive abilities. The aim of this review was to delineate a number of the more prominent treatments for ME/CFS into different categories and evaluate the methods and results of corresponding drug trials. Results indicate that: • antiviral drugs appear to show limited efficacy in treating ME/CFS over a broad demographic. • there is a lack of clinical research focusing on the use of specific cyclooxygenase-2 inhibitors [analgesic] to treat ME/CFS. • antidepressants may be of use in delivering improvements in the quality of life of patients with ME/CFS. • recalibration of endocrine-immune regulation may be involved in supporting the persistence of ME/CFS and may be responsible at least in part for its resistance to single agent interventions. Authors conclude that there is a great need for larger, longitudinal studies focused on a more clearly defined subset of ME/CFS as well as a greater consideration of potential synergies between interventions and the suitability of combination therapies.
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by prolonged periods of fatigue, chronic pain, depression, and a complex constellation of other symptoms. Currently, ME/CFS has no known cause, nor are the mechanisms of illness well understood. Therefore, with few exceptions, attempts to treat ME/CFS have been directed mainly toward symptom management. These treatments include antivirals, pain relievers, antidepressants, and oncologic agents as well as other single-intervention treatments. Results of these trials have been largely inconclusive and, in some cases, contradictory. Contributing factors include a lack of well-designed and -executed studies and the highly heterogeneous nature of ME/CFS, which has made a single etiology difficult to define. Because the majority of single-intervention treatments have shown little efficacy, it may instead be beneficial to explore broader-acting combination therapies in which a more focused precision-medicine approach is supported by a systems-level analysis of endocrine and immune co-regulation.
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Plant-Based Diets Are Associated With a Lower Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All-Cause Mortality in a General Population of Middle-Aged Adults.
Kim, H, Caulfield, LE, Garcia-Larsen, V, Steffen, LM, Coresh, J, Rebholz, CM
Journal of the American Heart Association. 2019;8(16):e012865
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Plant based diets have been associated with better health outcomes, however mixed results have been shown on their relationship with death by any cause and death due to heart disease. This cohort study of 15792 middle aged people aimed to determine if plant-based diets are associated with a lower risk of heart disease, death due to heart disease or death due to any cause and whether this was on a sliding scale depending on adherence to a healthful plant-based diet. The results showed that individuals following a plant-based diet had a 16% lower risk of heart disease, 32% lower risk of death due to heart disease and a 25% lower risk of death by any cause and individuals who followed a healthier plant-based diet were at an even lower risk of heart disease, death due to heart disease and death due to any cause. Interestingly when margarine was included in an individual’s diet, the decreased risk of heart disease was attenuated. It was concluded that higher adherence to a healthy plant-based diet was associated with a lower risk of heart disease, death due to heart disease and death by any cause. This study could be used by healthcare practitioners to recommend a plant-based diet to those at an increased risk of heart disease.
Abstract
Background Previous studies have documented the cardiometabolic health benefits of plant-based diets; however, these studies were conducted in selected study populations that had narrow generalizability. Methods and Results We used data from a community-based cohort of middle-aged adults (n=12 168) in the ARIC (Atherosclerosis Risk in Communities) study who were followed up from 1987 through 2016. Participants' diet was classified using 4 diet indexes. In the overall plant-based diet index and provegetarian diet index, higher intakes of all or selected plant foods received higher scores; in the healthy plant-based diet index, higher intakes of only the healthy plant foods received higher scores; in the less healthy plant-based diet index, higher intakes of only the less healthy plant foods received higher scores. In all indexes, higher intakes of animal foods received lower scores. Results from Cox proportional hazards models showed that participants in the highest versus lowest quintile for adherence to overall plant-based diet index or provegetarian diet had a 16%, 31% to 32%, and 18% to 25% lower risk of cardiovascular disease, cardiovascular disease mortality, and all-cause mortality, respectively, after adjusting for important confounders (all P<0.05 for trend). Higher adherence to a healthy plant-based diet index was associated with a 19% and 11% lower risk of cardiovascular disease mortality and all-cause mortality, respectively, but not incident cardiovascular disease (P<0.05 for trend). No associations were observed between the less healthy plant-based diet index and the outcomes. Conclusions Diets higher in plant foods and lower in animal foods were associated with a lower risk of cardiovascular morbidity and mortality in a general population.
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High-intensity interval training improves metabolic syndrome and body composition in outpatient cardiac rehabilitation patients with myocardial infarction.
Dun, Y, Thomas, RJ, Smith, JR, Medina-Inojosa, JR, Squires, RW, Bonikowske, AR, Huang, H, Liu, S, Olson, TP
Cardiovascular diabetology. 2019;18(1):104
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Metabolic syndrome (MetS) is associated with an eightfold increase in the risk of myocardial infarction (MI), and MI patients who have MetS have an increased risk of other cardiovascular events and recurrent MI. Exercise can improve MetS and is also recommended for patients after MI for rehabilitation. The aim of this retrospective study was to examine the effect of supervised high intensity interval training (HIIT) on MetS and body composition in overweight patients with MI. Of 56 patients who took part in a multidisciplinary rehabilitation program, 42 had engaged in HIIT and 14 in moderate-intensity continuous training (MICT), both groups had 36 supervised sessions over 12 weeks. Compared to MICT, the HIIT group demonstrated greater reductions in MetS. Better improvements in the HIIT group were seen in waist circumference, fasting blood glucose, triglycerides, diastolic blood pressure, body fat and lean mass, compared to the MICT group. There were no significant differences between groups in changes in BMI, HDL cholesterol and systolic blood pressure. The authors concluded that their findings support the use of HIIT to improve MetS in MI patients
Abstract
BACKGROUND To examine the effect of high-intensity interval training (HIIT) on metabolic syndrome (MetS) and body composition in cardiac rehabilitation (CR) patients with myocardial infarction (MI). METHODS We retrospectively screened 174 consecutive patients with MetS enrolled in CR following MI between 2015 and 2018. We included 56 patients who completed 36 CR sessions and pre-post dual-energy X-ray absorptiometry. Of these patients, 42 engaged in HIIT and 14 in moderate-intensity continuous training (MICT). HIIT included 4-8 intervals of high-intensity (30-60 s at RPE 15-17 [Borg 6-20]) and low-intensity (1-5 min at RPE < 14), and MICT included 20-45 min of exercise at RPE 12-14. MetS and body composition variables were compared between MICT and HIIT groups. RESULTS Compared to MICT, HIIT demonstrated greater reductions in MetS (relative risk = 0.5, 95% CI 0.33-0.75, P < .001), MetS z-score (- 3.6 ± 2.9 vs. - 0.8 ± 3.8, P < .001) and improved MetS components: waist circumference (- 3 ± 5 vs. 1 ± 5 cm, P = .01), fasting blood glucose (- 25.8 ± 34.8 vs. - 3.9 ± 25.8 mg/dl, P < .001), triglycerides (- 67.8 ± 86.7 vs. - 10.4 ± 105.3 mg/dl, P < .001), and diastolic blood pressure (- 7 ± 11 vs. 0 ± 13 mmHg, P = .001). HIIT group demonstrated greater reductions in body fat mass (- 2.1 ± 2.1 vs. 0 ± 2.2 kg, P = .002), with increased body lean mass (0.9 ± 1.9 vs. - 0.9 ± 3.2 kg, P = .01) than the MICT. After matching for exercise energy expenditure, HIIT-induced improvements persisted for MetS z-score (P < .001), MetS components (P < .05), body fat mass (P = .002), body fat (P = .01), and lean mass (P = .03). CONCLUSIONS Our data suggest that, compared to MICT, supervised HIIT results in greater improvements in MetS and body composition in MI patients with MetS undergoing CR.
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Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial.
Fowler, AA, Truwit, JD, Hite, RD, Morris, PE, DeWilde, C, Priday, A, Fisher, B, Thacker, LR, Natarajan, R, Brophy, DF, et al
JAMA. 2019;322(13):1261-1270
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Previous research has found that Vitamin C reduces widespread inflammation, as well as blood clotting and other vascular problems associated with sepsis. This randomised controlled trial of 167 patients in ICU with sepsis and acute respiratory distress syndrome (ARDS) were administered with high dose intravenous Vitamin C or placebo every 6 hours for 96 hours, to assess impacts on organ failure, inflammation and vascular injury. The authors found no statistically significant differences between the Vitamin C group and placebo in relation to organ failure, inflammation and vascular injury at 28 day follow up and call for further research. Healthcare practitioners may like to read critiques of this research available on Nutrition Evidence available here https://www.nutrition-evidence.com/article/31785700?term=31785700 and here https://www.nutrition-evidence.com/article/33117837?term=33117837
Abstract
Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.
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Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism.
Scheiman, J, Luber, JM, Chavkin, TA, MacDonald, T, Tung, A, Pham, LD, Wibowo, MC, Wurth, RC, Punthambaker, S, Tierney, BT, et al
Nature medicine. 2019;25(7):1104-1109
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Abstract
The human gut microbiome is linked to many states of human health and disease1. The metabolic repertoire of the gut microbiome is vast, but the health implications of these bacterial pathways are poorly understood. In this study, we identify a link between members of the genus Veillonella and exercise performance. We observed an increase in Veillonella relative abundance in marathon runners postmarathon and isolated a strain of Veillonella atypica from stool samples. Inoculation of this strain into mice significantly increased exhaustive treadmill run time. Veillonella utilize lactate as their sole carbon source, which prompted us to perform a shotgun metagenomic analysis in a cohort of elite athletes, finding that every gene in a major pathway metabolizing lactate to propionate is at higher relative abundance postexercise. Using 13C3-labeled lactate in mice, we demonstrate that serum lactate crosses the epithelial barrier into the lumen of the gut. We also show that intrarectal instillation of propionate is sufficient to reproduce the increased treadmill run time performance observed with V. atypica gavage. Taken together, these studies reveal that V. atypica improves run time via its metabolic conversion of exercise-induced lactate into propionate, thereby identifying a natural, microbiome-encoded enzymatic process that enhances athletic performance.
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Exposure to glyphosate-based herbicides and risk for non-Hodgkin lymphoma: A meta-analysis and supporting evidence.
Zhang, L, Rana, I, Shaffer, RM, Taioli, E, Sheppard, L
Mutation research. Reviews in mutation research. 2019;781:186-206
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Glyphosate is a highly effective broad-spectrum herbicide that is typically applied in mixtures known as glyphosate-based herbicides (GBHs). Glyphosate and its metabolites persist in food, water, and dust, potentially indicating that everyone may be exposed ubiquitously. The objective of this study was to focus on an a priori hypothesis - the highest biologically relevant exposure to GBHs, i.e., higher levels, longer durations and/or with sufficient lag and latency, will lead to increased risk of non-Hodgkin lymphoma (NHL) in humans. This study is a meta-analysis of six studies (one cohort and five case-control control studies) with almost 65,000 participants. Results demonstrated a significantly increased NHL risk in highly GBH-exposed individuals. Authors conclude that the overall evidence from human, animal, and mechanistic studies presented in this study, supports a compelling link between exposures to GBHs and increased risk for NHL.
Abstract
Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that includes the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% confidence interval, CI: 1.13-1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we calculated a meta-RR for NHL of 1.45 (95% CI: 1.11-1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed publicly available animal and mechanistic studies related to lymphoma. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between glyphosate / GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL or lymphomagenesis. Overall, in accordance with findings from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL.
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Broccoli consumption affects the human gastrointestinal microbiota.
Kaczmarek, JL, Liu, X, Charron, CS, Novotny, JA, Jeffery, EH, Seifried, HE, Ross, SA, Miller, MJ, Swanson, KS, Holscher, HD
The Journal of nutritional biochemistry. 2019;63:27-34
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Diet affects metabolic and gastrointestinal diseases, with the microbiome considered to be a mediating factor. Broccoli is a good source of fibre and phytochemicals including glucosinolates. The aim of this investigator-blinded, controlled feeding, randomised, crossover study was to evaluate the effects of broccoli on the composition and function of the microbiome. 18 healthy adults received 200 g cooked broccoli and 20 g raw daikon radish per day for 18 days in addition to a controlled, brassica-free diet or the same diet without the broccoli and daikon radish, with a 24-day washout period. A statistically significant increase in the ratio of Bacteroidetes to Firmicutes was observed following the broccoli intervention. When stratified by BMI above or below 25, this increase was only seen in those with a lower BMI whilst those with a higher BMI displayed a decrease in the ratio, although the latter was not statistically significant. In those with the lower BMI, there was also a correlation between the changes in the microbiota composition and glucosinolate metabolites. It was predicted that the involved changes would affect the functions of the endocrine system, transport and catabolism and energy metabolism. The authors concluded that eating broccoli may affect both the composition and the function of the microbiome.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Broccoli consumption at dosages of 200g per day were shown to change the composition of gastrointestinal microbiota, increasing Bacteroidetes and decreasing Firmicutes, and impact their function
- The observed results were strongest in those with a BMI of less than 26
- While interesting, the study only included 18 participants and therefore the results should be further confirmed.
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
There is growing evidence linking dysbiosis of the gastrointestinal microbiota and diet-induced gastrointestinal and metabolic diseases. Both long-term and acute dietary changes, fasting, eating frequency, and consumption of specific fibres and food phytochemicals play a role in shaping the composition and function of the microbiota, although evidence is lacking for specific foods. This study aimed to determine the impact of broccoli intake on the number of bacterial strains and their functional capacity.
Methods
This was a single-blind, randomised, crossover, complete feeding intervention. Study participants were healthy adults (n=18, females =10). Participants were requested to not eat Brassica vegetables for 3 weeks before the start of the study.
Subjects participated in two 18-day diet periods separated by a 24-hour washout, during which breakfast and dinner were consumed on site to observe compliance. The control diet was prepared using traditional American foods, excluding all Brassica vegetables. During the broccoli intervention period, participants consumed the same base diet with the addition of 200g of broccoli.
Faecal samples were collected on day 1, and day 16. Quantitative polymerase chain reaction was performed on bacterial strains. On day 17, time series plasma sampling and 24-hour urine collection was done.
Results
There was no difference in alpha diversity (a measure of microbiome diversity within a sample) between the two treatment periods. This indicates that no bacterial species were extinguished by broccoli treatment. Beta diversity analysis (a measure of the (dis)similarity between samples) indicated that bacterial communities were impacted by treatment (P=0.03).
After broccoli consumption, Bacteroidetes increased by 10% (P =0.03), while Firmicutes decreased by 8% (P=0.05). Overall the ratio of Bacteroidetes to Firmicutes increased by 37% (P=0.01) versus a 5% decrease in the control period. The Bacteroides genus increased by 6% (P=0.02) versus a 2% decrease in the control period.
Interestingly, the effects were most strong in those with a lower BMI (< 26 kg/m2) who had an increase in metabolites after broccoli consumption. Algorithms to predict the function of the microbiota showed that broccoli increased endocrine (P=0.05), energy metabolism (P=0.01), transport and catabolism (P=0.04) pathways.
Conclusion
Broccoli intake, at 200g daily, changes the composition and potentially impacts the function of the gut microbiota.
Clinical practice applications:
- Studies like this allow practitioners to focus on specific foods in specific quantities to positively alter the microbiota and their function
- Cruciferous vegetables, like broccoli, kale, cauliflower, cabbage, Brussel sprouts, are an important group as they contain fibre and phytonutrients such as glucosinolates. These compounds can be metabolised by the microbiota into active compounds with health benefits. This study has shown the bidirectional benefit of broccoli consumption in that it can positively impact the function and composition of the microbiota
- Interestingly, the results in this small study were driven by participants with a BMI of less than 26. Sub-group analysis found no statistically significant relationships in participants with BMI >26
- It is worth noting that it is possible that the addition of 5g of fibre from the broccoli is also contributing to the changes observed.
Considerations for future research:
- Larger, controlled feeding studies that isolate specific foods to identify their effects on the microbiota are needed
- Genetic sequencing for only a few bacterial myrosinases has been completed and therefore future studies should aim to assess the metabolic capabilities in faecal samples such as myrosinase activity
- While this study and others have shown changes in the types of bacteria after cruciferous vegetable consumption the consistency of results has been mixed potentially due to differing study designs and treatment dosages. Further studies to clarify and confirm these results would be beneficial
- To assess the function of the microbiota a predictive algorithm was used. This requires experimental confirmation by such methods as metabolite profiling and whole genome shotgun sequencing.
Abstract
The human gastrointestinal microbiota is increasingly linked to health outcomes; however, our understanding of how specific foods alter the microbiota is limited. Cruciferous vegetables such as broccoli are a good source of dietary fiber and phytonutrients, including glucosinolates, which can be metabolized by gastrointestinal microbes. This study aimed to determine the impact of broccoli consumption on the gastrointestinal microbiota of healthy adults. A controlled feeding, randomized, crossover study consisting of two 18-day treatment periods separated by a 24-day washout was conducted in healthy adults (n=18). Participants were fed at weight maintenance with the intervention period diet including 200 g of cooked broccoli and 20 g of raw daikon radish per day. Fecal samples were collected at baseline and at the end of each treatment period for microbial analysis. Beta diversity analysis indicated that bacterial communities were impacted by treatment (P=.03). Broccoli consumption decreased the relative abundance of Firmicutes by 9% compared to control (P=.05), increased the relative abundance of Bacteroidetes by 10% compared to control (P=.03) and increased Bacteroides by 8% relative to control (P=.02). Furthermore, the effects were strongest among participants with body mass index <26 kg/m2, and within this group, there were associations between bacterial relative abundance and glucosinolate metabolites. Functional prediction revealed that broccoli consumption increased the pathways involved in the functions of the endocrine system (P=.05), transport and catabolism (P=.04), and energy metabolism (P=.01). These results reveal that broccoli consumption affects the composition and function of the human gastrointestinal microbiota.
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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
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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.
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Relationship between vitamin D status and the vaginal microbiome during pregnancy.
Jefferson, KK, Parikh, HI, Garcia, EM, Edwards, DJ, Serrano, MG, Hewison, M, Shary, JR, Powell, AM, Hollis, BW, Fettweis, JM, et al
Journal of perinatology : official journal of the California Perinatal Association. 2019;39(6):824-836
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The composition of the vaginal microflora can significantly impact both reproductive and neonatal health. Numerous studies support the important role for sufficient serum or plasma concentrations of 25-hydroxy vitamin D (25(OH)D) during pregnancy in preventing negative outcomes. The study’s hypothesis was that vitamin D status is associated with the vaginal microbiome. This study is an analysis of a sub-cohort from a randomised, placebo-controlled clinical trial of vitamin D supplementation of pregnant women who were enrolled during the first trimester of pregnancy and followed until delivery. Participants (n=387) were randomised and received supplement: 191 received 400 IU (control group) and 196 received 4400 IU (treatment group). Results show that women in both the control and treatment groups displayed higher circulating 25(OH)D concentrations with increasing gestational age. Furthermore, among women of African ancestry, there was a negative correlation between 25(OH)D and abundance of Megasphaera [type of anaerobic microflora]. Authors conclude that certain vaginal bacteria are associated with plasma 25(OH)D concentration.
Abstract
OBJECTIVE Evidence supports an inverse association between vitamin D and bacterial vaginosis (BV) during pregnancy. Furthermore, both the vaginal microbiome and vitamin D status correlate with pregnancy outcome. Women of African ancestry are more likely to experience BV, to be vitamin D deficient, and to have certain pregnancy complications. We investigated the association between vitamin D status and the vaginal microbiome. STUDY DESIGN Subjects were assigned to a treatment (4400 IU) or a control group (400 IU vitamin D daily), sampled three times during pregnancy, and vaginal 16S rRNA gene taxonomic profiles and plasma 25-hydroxyvitamin D [25(OH)D] concentrations were examined. RESULT Gestational age and ethnicity were significantly associated with the microbiome. Megasphaera correlated negatively (p = 0.0187) with 25(OH)D among women of African ancestry. Among controls, women of European ancestry exhibited a positive correlation between plasma 25(OH)D and L. crispatus abundance. CONCLUSION Certain vaginal bacteria are associated with plasma 25(OH)D concentration.
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Fluoride exposure and kidney and liver function among adolescents in the United States: NHANES, 2013-2016.
Malin, AJ, Lesseur, C, Busgang, SA, Curtin, P, Wright, RO, Sanders, AP
Environment international. 2019;132:105012
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Fluoride is added to the water supply in some parts of the UK, US and Canada to help prevent tooth decay, but there is some concern that long-term exposure to fluoride could be harmful to health. Animal studies have indicated that fluoride may cause kidney and liver damage. This US study aimed to evaluate whether greater fluoride exposure is associated with altered kidney and liver function in adolescents. This cross-sectional study looked at data collected from the National Health and Nutrition Examination Survey (2013-2016). The average age of adolescents was 15 years. Fluoride levels were measured in blood and in household tap water. Higher levels of fluoride in the blood were associated with a lower estimated glomerular filtration rate, a higher blood uric acid concentration, and a lower blood urea nitrogen concentration. Higher levels of fluoride in tap water were associated with a lower blood urea nitrogen concentration. The researchers concluded that fluoride exposure may contribute to complex changes in kidney and liver function in US adolescents. However, researchers could not rule out the possibility that an altered kidney or liver function may impact the body’s ability to absorb or metabolise fluoride.
Abstract
BACKGROUND Hepato- and nephrotoxicity of fluoride have been demonstrated in animals, but few studies have examined potential effects in humans. This population-based study examines the relationship between chronic low-level fluoride exposure and kidney and liver function among United States (U.S.) adolescents. This study aimed to evaluate whether greater fluoride exposure is associated with altered kidney and liver parameters among U.S. youth. METHODS This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2013-2016). We analyzed data from 1983 and 1742 adolescents who had plasma and water fluoride measures respectively and did not have kidney disease. Fluoride was measured in plasma and household tap water. Kidney parameters included estimated glomerular filtration rate (calculated by the original Schwartz formula), serum uric acid, and the urinary albumin to creatinine ratio. Liver parameters were assessed in serum and included alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, gamma-glutamyl transferase, and albumin. Survey-weighted linear regression examined relationships between fluoride exposure and kidney and liver parameters after covariate adjustment. A Holm-Bonferroni correction accounted for multiple comparisons. RESULTS The average age of adolescents was 15.4 years. Median water and plasma fluoride concentrations were 0.48 mg/L and 0.33 μmol/L respectively. A 1 μmol/L increase in plasma fluoride was associated with a 10.36 mL/min/1.73 m2 lower estimated glomerular filtration rate (95% CI: -17.50, -3.22; p = 0.05), a 0.29 mg/dL higher serum uric acid concentration (95% CI: 0.09, 0.50; p = 0.05), and a 1.29 mg/dL lower blood urea nitrogen concentration (95%CI: -1.87, -0.70; p < 0.001). A 1 mg/L increase in water fluoride was associated with a 0.93 mg/dL lower blood urea nitrogen concentration (95% CI: -1.44, -0.42; p = 0.007). CONCLUSIONS Fluoride exposure may contribute to complex changes in kidney and liver related parameters among U.S. adolescents. As the study is cross-sectional, reverse causality cannot be ruled out; therefore, altered kidney and/or liver function may impact bodily fluoride absorption and metabolic processes.