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The American Journal of Clinical... Jun 2024A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated...
Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: A secondary analysis of the seAFOod polyp prevention trial.
BACKGROUND
A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for pro-inflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs.
OBJECTIVE
We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2 x 2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 months (ISRCTN05926847).
METHODS
Participant Indel genotype was determined by PCR blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention versus placebo. Presence of at least one Indel I allele and an interaction term (I allele x active intervention) were co-variates.
RESULTS
In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR] 0.92, 95% confidence interval 0.74, 1.16), mirroring original seAFOod trial analysis. However, presence of at least one I allele identified EPA users with a significant reduction in colorectal polyp number (IRR 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR.
CONCLUSIONS
The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted.
TRIAL REGISTRATION
The seAFOod polyp prevention trial and STOP-ADENOMA study are registered with https://www.isrctn.com as ISRCTN05926847.
PubMed: 38879016
DOI: 10.1016/j.ajcnut.2024.06.004 -
Complementary Therapies in Medicine Jun 2024Obesity is associated with many chronic non-communicable diseases, including hypertension, diabetes, cardiovascular and cerebrovascular diseases, cancer, gallbladder...
INTRODUCTION
Obesity is associated with many chronic non-communicable diseases, including hypertension, diabetes, cardiovascular and cerebrovascular diseases, cancer, gallbladder disease, bone and joint disorders, skin diseases, fatty liver disease, etc. (Wharton et al., 2020) The recent report revealed that overweight and obesity were prevalent in 60 % of the adult population. Several studies have been published to determine the effect of Hibiscus sabdariffa Linn. on obesity treatment, but the findings are still inconclusive. The purpose of this study was to determine the efficacy and safety of H. sabdariffa Linn in the treatment of obesity.
METHODS
We searched PubMed, EMBASE, and CENTRAL from inception to February 2024. Randomized controlled trials (RCTs) were included if they explored the effect of H. sabdariffa on one of the following outcomes: body weight, body mass index (BMI), waist circumference, and waist-to-hip ratio. A random-effects model was used to meta-analyze the data. I was used to quantify statistical heterogeneity among the included RCTs. PROSPERO registered protocol: CRD42023408880.
RESULTS
A total of six RCTs with 339 participants were included. Four trials used H. sabdariffa extract in capsules as the intervention of interest compared to placebo, while the other two trials used H. sabdariffa tea compared to black or green tea. Our meta-analyses showed that the mean difference in weight reduction between H. sabdariffa and control was - 0.27 kg (95 % confidence interval (CI); - 1.98 to 1.42, I = 0.0 %). The mean differences for BMI and waist circumference reduction were - 0.06 kg/m (95 % CI; - 0.58 to 0.47, I = 0.0 %) and - 0.20 centimeters (95 % CI; - 2.06 to 1.66, I = 0.00 %). No safety concerns were reported in the included studies.
CONCLUSION
Our study did not show a clinical benefit of H. sabdariffa extract in obesity treatment. However, further high-quality RCTs with a longer treatment duration and a standard dose are still warranted.
PubMed: 38878905
DOI: 10.1016/j.ctim.2024.103063 -
Diabetology & Metabolic Syndrome Jun 2024Prediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is...
BACKGROUND
Prediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is thought to be lifestyle modification. Pharmacological therapy, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), were not well addressed in the literature and were only evaluated in trials as secondary and exploratory outcomes with a limited sample size. Here, GLP-1RAs are evaluated as a comprehensive therapy approach for patients with prediabetes.
METHODS
A comprehensive search of Web of Science, SCOPUS, PubMed, and Cochrane was performed on May 5, 2023, to retrieve randomized controlled trials (RCTs) comparing the effect of GLP-1RAs to placebo and/or lifestyle modification on prediabetes reversion to normoglycemia, prevention of overt diabetes, glycemic control, anthropometric parameters, and lipid profiles. Review Manager (RevMan) version 5.4 was used. The quality of RCTs was assessed using the revised version of the Cochrane Risk of Bias Tool. GRADE was performed to evaluate the certainty of evidence.
RESULTS
Twelve trials involving 2903 patients in the GLP-1RAs group and 1413 in the control group were included in the meta-analysis. Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43), P < 0.00001]. Significant reductions in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL were observed in the GLP-1RAs arm (P < 0.05). However, higher incidences of gastrointestinal disorders were reported in the GLP-1RAs group (P < 0.05).
CONCLUSIONS
GLP-1RAs combined with lifestyle modification proved to be a more effective therapy for managing prediabetic patients than lifestyle modification alone, with a tolerable safety profile. Future guidelines should consider GLP-1RAs as an adjunct to lifestyle modification in the management of prediabetic patients to provide better management and improve treatment adherence.
PubMed: 38877565
DOI: 10.1186/s13098-024-01371-3 -
European Journal of Internal Medicine Jun 2024Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The...
BACKGROUND
Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects.
METHODS
This was a phase III, 6-month, 25-site, randomized, placebo-controlled clinical trial using AD04 to treat DSM-V-categorized AUD individuals who were pre-stratified into the endophenotypes of heavy or very heavy drinking individuals and possessed a pre-defined profile of genetic variants related to the serotonin transporter and serotonin-3AB receptor. Participants (N = 303) presented moderate to severe AUD, >80 % were men, mostly in their fifties, and >95 % were of European descent. Low-dose AD04 (approx. 033 mg twice daily) or a matching placebo was administered twice daily for 6 months. Brief Behavioral Compliance Enhancement Treatment (BBCET [53]) was administered every two weeks to enhance medication compliance and clinic attendance.
RESULTS
There was a significant reduction in the monthly percentage of heavy drinking days, PHDD (-46·7 % (2·7 %), 95 %CI: -52·1 % to -41·2 % vs. -38·1 % (2·9 %), 95 %CI: -43·8 % to -32·5 %, respectively; LS mean difference=-8·5 %; p = 0.03) among AD04-treated vs. placebo-receiving heavy drinking individuals at month 6. Heavy drinking individuals were also less likely to be diagnosed with AUD [Month 1: -32·0 % (2·8 %), 95 %CI: -37·5 % to -26·5 % vs. -23·2 % (2·9 %), 95 %CI: -28·9 to -17·5 %; LS mean difference= -8·8 %; p = 0·026)], and improved on the WHO quality of life BREF scale with a significant effect for at least a 1-level downward shift (OR = 3.4; 95 % CI: 1·03-11·45, p = 0·044). Importantly, heavy drinking individuals, as distinct from very heavy drinking individuals, were the bio-psychosocial endophenotype more predictive of therapeutic response to AD04. AD04 had an exceptional safety and tolerability profile, like the placebo's.
CONCLUSIONS
In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure.
PubMed: 38876929
DOI: 10.1016/j.ejim.2024.06.001 -
Complementary Therapies in Medicine Jun 2024The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials... (Review)
Review
OBJECTIVE
The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials (RCTs) to evaluate the effectiveness of GC on leptin levels.
METHODS
A thorough literature search was carried out using different online databases, including Scopus, Web of Science, PubMed, and Google Scholar, until May 25, 2024. Using random effects, weighted mean differences (WMDs) and corresponding 95 % confidence intervals (CIs) were computed. Standard procedures were followed to account for publication bias, study quality, and statistical heterogeneity.
RESULTS
In this meta-analysis, a total of eight eligible trials with 330 participants were ultimately included. Quality assessment showed that half of the included trials were considered to have fair quality, while the other half were deemed to have poor quality. Our analysis, with no indication of publication bias, showed a significantly decreased effect of GC on leptin compared with the placebo (WMD: -5.01 ng/ml; 95 % CI: -9.22 to -0.80, p = 0.02). However, significant heterogeneity was detected between studies (I =93.5 %, p < 0.001). The Hartung-Knapp adjustment did not affect our results. Subgroup analysis revealed that GC consumption represents the most effects in trials with sample size ≥ 50 (WMD: -3.63 ng/ml; 95 % CI [-5.51, -1.76], p < 0.001), and mean age of participants ≥ 30 years (WMD: -7.43 ng/ml; 95 % CI [-9.31, -5.56], p < 0.001).
CONCLUSIONS
The findings of the present study showed that leptin levels might decline following GC administration.
REGISTRATION NUMBER
CRD42023486370.
PubMed: 38876392
DOI: 10.1016/j.ctim.2024.103060 -
European Journal of Sport Science Jun 2024Citrulline malate (CM) is purported to be an ergogenic aid during various types of exercise performance. However, the effects of CM on repeated sprint performance (RSP)... (Randomized Controlled Trial)
Randomized Controlled Trial
Citrulline malate (CM) is purported to be an ergogenic aid during various types of exercise performance. However, the effects of CM on repeated sprint performance (RSP) are under-explored. In a placebo-controlled, double-blind, counterbalanced cross-over design, male university-level team sport athletes (n = 13) performed two familiarization trials, after which CM or placebo (PLA) (8 × 1 g tablets each day) were taken on the 2 days prior to, and with breakfast on the morning of, each main experimental trial. The main experimental trials employed a RSP protocol consisting of 10 repetitions of 40 m maximal shuttle run test (MST) with a 30 s interval between the start of each sprint. Sprint times and heart rate were recorded throughout the MST, and blood lactate concentrations were measured before, immediately after, and 5 min after completing the MST. CM resulted in better RSP compared to PLA, as indicated by a lower sprint performance decrement (S: CM, 4.68% ± 1.82% vs. PLA, 6.10% ± 1.83%; p = 0.03; ES = 0.77), which was possibly influenced by the fastest sprint time being faster in CM (CM, 8.16 ± 0.34 s vs. PLA, 8.29 ± 0.39 s; p = 0.011; ES = 0.34). There were no differences between CM and PLA in average sprint time (p = 0.54), slowest sprint time (p = 0.48), blood lactate concentrations (p = 0.73) or heart rate (p = 0.18), nor was there a condition × time interaction effect across the 10 sprints (p = 0.166). Three days of CM supplementation (8 g daily) attenuated the sprint performance decrement during short-duration high-intensity exercise in the form of running RSP in male university-level team sport athletes.
Topics: Humans; Male; Running; Athletic Performance; Cross-Over Studies; Double-Blind Method; Young Adult; Citrulline; Dietary Supplements; Heart Rate; Lactic Acid; Malates; Athletes; Team Sports; Performance-Enhancing Substances; Adult
PubMed: 38874989
DOI: 10.1002/ejsc.12090 -
European Journal of Sport Science Jun 2024We investigated the effect of ischemic preconditioning (IPC) with and without caffeine supplementation on mean power output (MPO) during a 4-min cycling time-trial (TT).... (Randomized Controlled Trial)
Randomized Controlled Trial
We investigated the effect of ischemic preconditioning (IPC) with and without caffeine supplementation on mean power output (MPO) during a 4-min cycling time-trial (TT). In a double-blinded, randomized, crossover-design, 11 trained men performed a TT on 4 days separated by ∼1 week. One hour before TT, participants ingested either caffeine (3 mg kg bw) or placebo pills, after which femoral blood-flow was either restricted with occlusion cuffs inflated to ∼180 mmHg (IPC), or sham-restricted (0-10 mmHg; Sham) during 3 × 2-min low-intensity cycling (10% of incremental peak power output). Then, participants performed a standardized warm-up followed by the TT. Plasma lactate and K concentrations and ratings of perceived exertion (RPE) were measured throughout trials. TT MPO was 382 ± 17 W in Placebo + Sham and not different from Placebo + IPC (-1 W; 95% CI: -9 to 7; p = 0.848; d: 0.06), whereas MPO was higher with Caffeine + Sham (+6W; 95% CI: -2 to 14; p = 0.115; d: 0.49) and Caffeine + IPC (+8 W; 95% CI: 2-13; p = 0.019; d: 0.79) versus Placebo + Sham. MPO differences were attributed to caffeine (caffeine main-effect: +7 W; 95% CI: 2-13; p = 0.015; d: 0.54. IPC main-effect: 0 W; 95% CI: -6 to 7; p = 0.891; d: 0.03; caffeine × IPC interaction-effect: p = 0.580; d: 0.17). TT RPE and plasma variables were not different between treatments. In conlcusion, IPC with co-ingestion of placebo does not improve short-term high-intensity performance in trained men versus a double-placebo control (Placebo + Sham) and does not additively enhance performance with caffeine. These data do not support IPC as a useful strategy for athletes prior to competition but confirms caffeine's performance-enhancing effect.
Topics: Humans; Caffeine; Male; Double-Blind Method; Athletic Performance; Ischemic Preconditioning; Young Adult; Bicycling; Cross-Over Studies; Adult; Lactic Acid; Potassium; Performance-Enhancing Substances; Physical Exertion
PubMed: 38874987
DOI: 10.1002/ejsc.12088 -
European Journal of Sport Science Jun 2024This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin...
The effect of 12 weeks of aerobic exercise training with or without saffron supplementation on diabetes-specific markers and inflammation in women with type 2 diabetes: A randomized double-blind placebo-controlled trial.
This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin resistance in obese women diagnosed with type 2 diabetes (T2D). A total of 44 women with T2D (mean age: 54.12 ± 5.63 years, mean BMI: 31.15 ± 1.50 kg/m, HbA1c: 85 ± 4.2 mmol/mol) were included in a randomized, double-blind, placebo-controlled study. We were randomly assigned to one of four groups (n = 11 per group): saffron + training (ST), placebo + training (PT), saffron supplement (SS), and placebo (P). The ST and PT groups completed 12 weeks of AT (three sessions per week of mild to moderate intensity). The ST and SS groups were administered a daily dose of 200 mg of saffron powder for 12 weeks. Fasting blood samples were collected 48 h before the first AT session and/or nutritional supplementation and 48 h after the last AT session and/or nutritional supplementation. Post-evaluation, homeostatic model assessment of insulin resistance value (HOMA-IR, p < 0.001) and serum levels of glucose (p < 0.001), fibrinogen (FIB, p < 0.001), homocysteine (HCY, p < 0.001), interleukin-6 (IL-6, p < 0.001), and tumor necrosis factor α (TNFα, p < 0.001) showed significant reduction in the ST, PT, and SS groups compared to the P group (p < 0.05). In particular, the ST group showed a more significant reduction in all variables compared to the PT and SS groups (p < 0.05). Our results suggest that a 12-week intervention with AT and saffron supplementation can independently improve markers related to hemostasis, inflammation, and insulin resistance. However, their combination showed the greatest effectiveness on the above markers.
PubMed: 38874882
DOI: 10.1002/ejsc.12125 -
Supportive Care in Cancer : Official... Jun 2024To examine the effect of individualized reminiscence therapy on the management of global distress and physical and psychological symptoms, life satisfaction and... (Randomized Controlled Trial)
Randomized Controlled Trial
The effectiveness of reminiscence therapy on the symptom management, the life satisfaction, and the self-transcendence in palliative care patients: a randomized controlled trial.
PURPOSE
To examine the effect of individualized reminiscence therapy on the management of global distress and physical and psychological symptoms, life satisfaction and self-transcendence levels of palliative care patients.
METHODS
In a single-center palliative care service in western Turkey, 48 patients without cognitive impairment and able to communicate were included in the study. However, 44 patients completed the study. Patients who met the inclusion criteria were randomly assigned to the reminiscence therapy (intervention), unstructured social interviewing (placebo), and control groups (16 people for each group) before the start of the study. The sessions for the interview and placebo groups were conducted face-to-face in the patient's room (while the patient was sitting or lying down) for 15 days (2 weeks), every other day, for a total of eight sessions (each session was approximately 30 min). Data collection instruments-the Memorial Symptom Assessment Scale, the Contentment with Life Assessment Scale, and the Self-Transcendence Scale-were collected at baseline (first day) and after the intervention (day 15). Statistical significance level was accepted as p < 0.05.
RESULTS
There was no decrease in physical and total symptom burden (p > 0.05). There were significant reductions in general distress and psychological symptoms in the intervention and placebo groups within the group (p < 0.05), but there were no significant differences between the control group and all groups when compared (p > 0.05). Group × time interactions were statistically significant for life satisfaction and self-transcendence (p < 0.001), and there was a substantial increase in the intervention group compared to the other groups.
CONCLUSION
It may be recommended that reminiscence therapy intervention be included in routine nursing care as it may contribute positively to the psychological recovery of palliative care patients approaching the end of life.
TRIAL REGISTRATION
ClinicalTrails.gov (Registration number: NCT05242016). Prospectively registered on 1 February 2022.
Topics: Humans; Male; Female; Palliative Care; Middle Aged; Personal Satisfaction; Aged; Turkey; Adult; Neoplasms; Psychotherapy
PubMed: 38874763
DOI: 10.1007/s00520-024-08626-9