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Effects of the 5:2 intermittent fasting diet on non-alcoholic fatty liver disease: A randomized controlled trial.
Kord Varkaneh, H, Salehi Sahlabadi, A, Găman, MA, Rajabnia, M, Sedanur Macit-Çelebi, M, Santos, HO, Hekmatdoost, A
Frontiers in nutrition. 2022;9:948655
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Non-alcoholic fatty liver disease (NAFLD) is associated with modifiable risk factors such as obesity, diabetes and metabolic syndrome. The 5:2 diet is an intermittent fasting regimen in which you fast for two days and eat liberally for five days per week. Time-restricted eating or intermittent fasting is a great way to limit energy intake and manage metabolic markers, making fasting diets like the 5:2 a viable option for the treatment of NAFLD. In this study, fifty patients with NAFLD were randomly assigned to either the intermittent fasting (5:2) or the control group. In the 5:2 group, the intervention resulted in a modest reduction in calorie intake. Participants on the 5:2 diet showed significant improvements in biomarkers of NAFLD, inflammatory markers, and body composition after 12 weeks of intervention. An evaluation of the effectiveness of a 5:2 diet on improving lipid profiles and diabetes requires further robust research. This study provides healthcare professionals insight into the benefits of implementing intermittent fasting as a cost-effective and safe therapeutic method.
Abstract
Background and aims: Dietary regimens are crucial in the management of non-alcoholic fatty liver disease (NAFLD). The effects of intermittent fasting (IF) have gained attention in this regard, but further research is warranted. Thus, we aimed to ascertain the overall effects of the 5:2 IF diet (5 days a week of normal food intake and 2 consecutive fasting days) in patients with NAFLD compared to a control group (usual diet). Methods and results: A 12-week randomized controlled trial was performed to evaluate the effects of the 5:2 IF diet on anthropometric indices, body composition, liver indices, serum lipids, glucose metabolism, and inflammatory markers in patients with NAFLD. The IF group (n = 21) decreased body weight (86.65 ± 12.57-82.94 ± 11.60 kg), body mass index (30.42 ± 2.27-29.13 ± 1.95 kg/m2), waist circumference (103.52 ± 6.42-100.52 ± 5.64 cm), fat mass (26.64 ± 5.43-23.85 ± 5.85 kg), fibrosis (6.97 ± 1.94-5.58 ± 1.07 kPa), steatosis scores/CAP (313.09 ± 25.45-289.95 ± 22.36 dB/m), alanine aminotransferase (41.42 ± 20.98-28.38 ± 15.21 U/L), aspartate aminotransferase (34.19 ± 10.88-25.95 ± 7.26 U/L), triglycerides (171.23 ± 39.88-128.04 ± 34.88 mg/dl), high-sensitivity C-reactive protein (2.95 ± 0.62 -2.40 ± 0.64 mg/L), and cytokeratin-18 (1.32 ± 0.06-1.19 ± 0.05 ng/ml) values compared to the baseline and the end of the control group (n = 23)-p ≤ 0.05 were considered as significant. However, the intervention did not change the levels of high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, fasting blood sugar, insulin, HOMA-IR, and total antioxidant capacity. Conclusion: Adhering to the 5:2 IF diet can reduce weight loss and related parameters (fat mass and anthropometric indicators of obesity), as well as hepatic steatosis, liver enzymes, triglycerides, and inflammatory biomarkers in patients with NAFLD.
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Adverse Effects of Excessive Zinc Intake in Infants and Children Aged 0-3 Years: A Systematic Review and Meta-Analysis.
Ceballos-Rasgado, M, Lowe, NM, Mallard, S, Clegg, A, Moran, VH, Harris, C, Montez, J, Xipsiti, M
Advances in nutrition (Bethesda, Md.). 2022;13(6):2488-2518
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The upper limit of a nutrient’s intake has been defined as the maximum intake from food, water, and supplements that is unlikely to pose risk of adverse health effects to most individuals in the general population. The aim of this study was to determine the levels of zinc intake at which adverse effects are observed in children aged 0–3 years. This study is a systematic review and meta-analysis of fifty-eight articles from fifty-five studies. Almost all studies were randomised controlled studies (n=52) and the rest were quasi-experimental studies. Results show: - that zinc supplementation had a significant adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, haemoglobin, haematocrit, and the odds of anaemia in ≥1 of the subgroups of pooled data. - a significant reduction of the lactulose:mannitol ratio. - that there weren’t significant effects of zinc supplementation on c-reactive protein, erythrocyte superoxide dismutase [antioxidant enzyme], zinc protoporphyrin [chemical compound], blood cholesterol, or iron deficiency anaemia Authors conclude that the recommended maximum zinc doses might need to be adjusted for children at risk or recovering from iron or copper deficiency. Additionally, the study’s findings may be used to undertake dose–response modelling to estimate tolerable upper intake levels of zinc in children aged 0–3 years.
Abstract
Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.
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Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial.
Holm Nielsen, S, Sardar, S, Siebuhr, AS, Schlemmer, A, Schmidt, EB, Bay-Jensen, AC, Karsdal, MA, Christensen, JH, Kristensen, S
Rheumatology international. 2021;41(6):1065-1077
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Psoriatic arthritis is a chronic inflammatory condition that causes joint pain and swelling along with red, flaky, and scaly skin. Inflammation affects the extracellular matrix, which comprises proteins and molecules that support cartilage, bone, and soft tissues in joints. A high level of collagen fragments is released into the bloodstream as a result. Fish oils and fish are good sources of n-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid and docosahexaenoic acid. Inflammation and joint pain have been shown to be reduced by n-3 PUFA in previous studies. This randomised, double-blinded, placebo-controlled study randomly assigned 142 patients with psoriatic arthritis to receive 3g n-3 PUFA (50% EPA and 50% DHA) or 3g of olive oil as the control for 24 weeks. Taking N-3 PUFA supplementation did not affect extracellular matrix turnover in psoriatic arthritis patients. This may be due to the anti-inflammatory properties of olive oil, which was used as a control, and to the short duration of the study. The benefits of using n-3 PUFA as a therapeutic strategy in patients with psoriatic arthritis need to be evaluated in larger, robust long-term studies. Furthermore, the clinical efficacy of n-3 PUFA cannot be distinguished since 75% of the patients took anti-rheumatic drugs. A study like this can provide healthcare professionals with insights into the potential benefits of n-3 PUFAs, which may aid them in making therapeutic decisions.
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.
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PROFAST: A Randomized Trial Assessing the Effects of Intermittent Fasting and Lacticaseibacillus rhamnosus Probiotic among People with Prediabetes.
Tay, A, Pringle, H, Penning, E, Plank, LD, Murphy, R
Nutrients. 2020;12(11)
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The prevalence of diabetes is increasing worldwide, and with it, the risk of cardiovascular disease is also increasing. Intermittent fasting has been shown to reduce weight and improve glycaemic control. Weight control and glycaemic control were also improved with probiotic Lacticaseibacillus rhamnosus HN001 supplementation. This pilot, 12-week, double-blinded, two-armed, randomized 1:1 study aimed to investigate the combined effects of intermittent fasting with daily probiotic Lacticaseibacillus rhamnosus HN001 supplementation on glycaemic management in participants with prediabetes. For two days, participants restricted their calorie intake to 600-650 kcal, followed by five days of ad libitum consumption (5:2). Intermittent fasting for 12 weeks improved glycaemic control (reduced HbA1c) and reduced body weight by 5%. The supplementation with Lacticaseibacillus rhamnosus HN001 did not significantly improve these outcomes. Probiotic supplementation significantly improved mental health and social functioning in participants. There is a need for further large, robust studies to assess the effects of intermittent fasting alone and when it is combined with different exercise forms and different prebiotic and probiotic supplements on cardiometabolic markers and mental health. The findings of this study may be useful to healthcare professionals in understanding the effects of fasting on metabolism as well as the psychological benefits of Lacticaseibacillus rhamnosus HN001 supplementation.
Abstract
Both intermittent fasting and specific probiotics have shown promise in improving glucose tolerance with a potential for synergistic effects through alterations to gut microbiota. In this randomized, double-blinded, two-arm feasibility study, we investigated whether intermittent fasting, supplemented with Lacticaseibacillus rhamnosus HN001 probiotic, reduces HbA1c in individuals with prediabetes. All participants with HbA1c 40-50 mmol/mol commenced intermittent fasting (2 days per week of calorie restriction to 600-650 kcal/day) and were randomized 1:1 to either daily probiotic (Lacticaseibacillus rhamnosus HN001) or placebo for 12 weeks. The primary outcome was a change in HbA1c. Secondary outcomes included changes in anthropometry, body composition, glucoregulatory markers, lipids, hunger hormones, liver enzymes, inflammatory markers, gut hormones, calorie and macronutrient intake, quality of life, hunger, mood and eating behavior. Of 33 participants who commenced the trial, 26 participants (mean age 52 years, body mass index (BMI) 34.7 kg/m2) completed the intervention (n = 11 placebo, n = 15 probiotic). HbA1c decreased from 43 ± 2.7 mmol/mol to 41 ± 2.3 mmol/mol, p < 0.001, with average of 5% weight loss. No significant between-group differences were seen in primary or secondary outcomes except for social functioning (p = 0.050) and mental health (p = 0.007) scores as improvements were seen in the probiotic group, but not in the placebo group. This study shows additional psychological benefits of probiotic supplementation during intermittent fasting to achieve weight loss and glycemic improvement in prediabetes.
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Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy.
Pirinen, E, Auranen, M, Khan, NA, Brilhante, V, Urho, N, Pessia, A, Hakkarainen, A, Kuula, J, Heinonen, U, Schmidt, MS, et al
Cell metabolism. 2020;31(6):1078-1090.e5
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Nicotinamide adenine dinucleotide (NAD+) metabolite and its derivatives are fundamental orchestrators of daily homeostasis in our tissues. The relative amounts of NAD forms (NAD+, NADH, NADP, and NADPH) and their cofactor functions to drive metabolism to either catabolic or anabolic direction, deciding whether nutrients are broken down to synthesize ATP (adenosine 5′-triphosphate), the cellular energy currency or used as building blocks for growth and repair. An increased NAD+ /NADH ratio is a signal for a low nutrient state activating cellular fasting responses. The main question of this study was whether NAD+ levels are depleted in mitochondrial dysfunction, as mitochondria are regulating NAD+ concentrations, and if so, whether NAD+ deficiency can be restored in the tissues of the patients. Results show that mitochondrial muscle disease causes NAD+ deficiency, a myopathy-induced vitamin B3 deficiency, a metabolic pellagra. Furthermore, NAD+ levels can be rescued by a potent NAD+ booster niacin, a vitamin B3 form. Authors conclude that their findings (1) underscore the potent role of micronutrient vitamin B3 as a metabolic modifier; (2) identify NAD+ deficiency as a contributor to mitochondrial myopathy progression; (3) point to usefulness of niacin therapy for progressive external ophthalmoplegia patients; (4) introduce blood NAD+ test as a tool to identify and follow-up NAD+ deficiency; (5) indicate that correction of metabolome and function can occur without correction of transcriptional stress responses, emphasizing importance of metabolomic analysis in follow-up of treatment efficacy.
Abstract
NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open. Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.govNCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy.