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The Effect of Walnut Intake on Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Alshahrani, SM, Mashat, RM, Almutairi, D, Mathkour, A, Alqahtani, SS, Alasmari, A, Alzahrani, AH, Ayed, R, Asiri, MY, Elsherif, A, et al
Nutrients. 2022;14(21)
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The prevalence of cardiovascular disease increases as the modifiable risk factors increase, such as metabolic syndrome, obesity, type 2 diabetes, dyslipidaemia, and high blood pressure. Walnuts are a rich source of anti-inflammatory polyunsaturated fatty acids and omega-3 fatty acids. Walnuts are also known for their antioxidant properties and have been found to improve dyslipidaemia by reducing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). This systematic review and meta-analysis of thirteen randomised controlled trials evaluated the effects of walnut intake on lipid profile. Most of the included studies used walnut dosage ranging from 15 g to 99 g/day for six to sixteen weeks of intervention. The results of this systematic review and meta-analysis showed significant improvements in TC, LDL-c, and triglyceride (TG) levels. Subgroup analysis revealed greater improvement in TC, LDL-c, and TG in overweight and other comorbidities but had normal levels of TC and LDL-C. Additionally, female participants showed greater improvements in TG levels, followed by the walnut intervention. Intervention duration also affected the beneficial effect of the walnut intervention. Further robust studies are required to determine the effects of walnut intake on cardiovascular disease risk reduction due to the high heterogeneity between the included studies. However, healthcare professionals can use the results of this research to understand the benefits of including walnuts as part of a healthy diet and their impact on reducing dyslipidaemia.
Abstract
Cardiovascular diseases (CVD) are the leading causes of death worldwide. Dyslipidemia is a cardiometabolic risk factor of CVD, yet it can be modifiable. Walnuts have been suggested as a dietary intervention to improve the lipid profile. Therefore, we reviewed the literature to assess the evidence linking walnut intake to the improvement of blood lipids, including total cholesterol (TC), low-density lipoprotein (LDL-C) cholesterol, high-density lipoprotein (HDL-C) cholesterol, and triglycerides (TG). PubMed and Embase databases were searched from 2010 up to March 2022. We limited our search to randomized controlled trials conducted on humans and published in English during the specified period. Cochrane's risk of bias tool for interventional studies was used. A random-effects model was used for the meta-analysis, and weighted mean differences were obtained (WMD) Thirteen trials from the U.S., Europe, and Asia were included. Walnut intake was associated with significant reductions in TC (WMD: -8.58 mg/dL), LDL-C (WMD: -5.68 mg/dL), and TG (WMD: -10.94 mg/dL). Walnut consumption was not associated with HDL-C. Subgroup analysis showed that overweight/obese and those with comorbidities had more lipid improvement. A longer trial duration did result in further improvements. However, our results may be prone to bias due to extraneous confounding factors. Additionally, levels of heterogeneity were considerable for some outcomes of interest. Results from this meta-analysis provide evidence for the health benefits of walnuts on blood lipids. Walnuts possibly reduce the risk of CVD; thus, they can be successfully added to a dietary pattern to enhance health benefits.
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Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial.
Alfadhel, M, Nashabat, M, Saleh, M, Elamin, M, Alfares, A, Al Othaim, A, Umair, M, Ahmed, H, Ababneh, F, Al Mutairi, F, et al
Orphanet journal of rare diseases. 2021;(1):422
Abstract
BACKGROUND Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias. METHODS The study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay. RESULTS Thirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels. CONCLUSION Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.
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6-Pyruvoyltetrahydropterin Synthase Deficiency: Review and Report of 28 Arab Subjects.
Almannai, M, Felemban, R, Saleh, MA, Faqeih, EA, Alasmari, A, AlHashem, A, Mohamed, S, Sunbul, R, Al-Murshedi, F, AlThihli, K, et al
Pediatric neurology. 2019;:40-47
Abstract
BACKGROUND Tetrahydrobiopterin is an essential cofactor for the hydroxylation of aromatic amino acids phenylalanine, tyrosine, and tryptophan. Therefore, tetrahydrobiopterin deficiency results in hyperphenylalaninemia as well as dopamine and serotonin depletion in the central nervous system. The enzyme 6-pyruvoyltetrahydropterin synthase catalyzes the second step of de novo synthesis of tetrahydrobiopterin, and its deficiency is the most frequent cause of tetrahydrobiopterin metabolism disorders. METHOD We conducted a retrospective chart review of 28 subjects from 24 families with molecularly confirmed 6-pyruvoyltetrahydropterin synthase deficiency from six centers in three Arab countries. We reviewed clinical, biochemical, and molecular data. We also reviewed previously published cohorts of subjects with 6-pyruvoyltetrahydropterin synthase deficiency. RESULTS Similar to previous observations, we show that early treatment (less than two months) is associated with better outcome. We identify eight PTS variants in 24 independent families. The most common variant is (c.238A>G; p.M80V) with an allele count of 33%. We also identify one novel variant (c.2T>G; p.?). CONCLUSION The deficiency of 6-pyruvoyltetrahydropterin synthase is relatively common in the Arab population and should be considered in individuals with hyperphenylalaninemia. More natural history studies with comprehensive biochemical and molecular genetics data are needed for a robust base for the development of future therapy.
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Evaluation of long-term effectiveness of the use of carglumic acid in patients with propionic acidemia (PA) or methylmalonic acidemia (MMA): study protocol for a randomized controlled trial.
Nashabat, M, Obaid, A, Al Mutairi, F, Saleh, M, Elamin, M, Ahmed, H, Ababneh, F, Eyaid, W, Alswaid, A, Alohali, L, et al
BMC pediatrics. 2019;(1):195
Abstract
INTRODUCTION Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive inborn errors of metabolism characterized by hyperammonemia due to N-acetylglutamate synthase (NAGS) dysfunction. Carglumic acid (Carbaglu®; Orphan Europe Ltd.) is approved by the US Food and Drug Administration (USFDA) for the treatment of hyperammonemia due hepatic NAGS deficiency. Here we report the rationale and design of a phase IIIb trial that is aimed at determining the long-term efficacy and safety of carglumic acid in the management of PA and MMA. METHODS This prospective, multicenter, open-label, randomized, parallel group phase IIIb study will be conducted in Saudi Arabia. Patients with PA or MMA (≤15 years of age) will be randomized 1:1 to receive twice daily carglumic acid (50 mg/kg/day) plus standard therapy (protein-restricted diet, L-carnitine, and metronidazole) or standard therapy alone for a 2-year treatment period. The primary efficacy outcome is the number of emergency room visits due to hyperammonemia. Safety will be assessed throughout the study and during the 1 month follow-up period after the study. DISCUSSION Current guidelines recommend conservative medical treatment as the main strategy for the management of PA and MMA. Although retrospective studies have suggested that long-term carglumic acid may be beneficial in the management of PA and MMA, current literature lacks evidence for this indication. This clinical trial will determine the long-term safety and efficacy of carglumic acid in the management of PA and MMA. TRIAL REGISTRATION King Abdullah International Medical Research Center ( KAIMRC ): (RC13/116) 09/1/2014. Saudi Food and Drug Authority (SFDA) (33066) 08/14/2014. ClinicalTrials.gov (identifier: NCT02426775) 04/22/2015.