Acid Supplementation In Patients Research Articles

Therapeutic advantages of omega-3 fatty acid supplementation in patients with schizophrenia – a systematic review

Introduction and aim. In patients with schizophrenia, omega-3 (n-3) polyunsaturated fatty acids (PUFAs) treatment was found to ameliorate the cardiovascular, metabolic, and inflammatory problems caused by antipsychotic medication and even reduce the need for medication by 20%. In this study, we evaluated the potential therapeutic effects of n-3 PUFA supplementation in patients with schizophrenia. Material and methods. The PRISMA guidelines were followed in conducting this systematic review. The Embase, MEDLINE, Web of Science, and Google Scholar databases were searched electronically. The first search yielded 50 papers in total. Subse quently, 43 publications that did not meet our eligibility requirements were removed, and seven articles were selected. Analysis of the literature. The analysis showed that n-3 PUFA supplementation and the placebo group both decreased their psychotic (PANSS and GAF scales) and Calgary Depression Scale symptomatology and boosted their functional ability (GAF) when used as an adjuvant to antipsychotic medication. When administered as a monotherapy with a metabolic antioxidant, n-3 PUFA supplementation proved beneficial for treating schizophrenia. In patients with schizophrenia, n-3 PUFAs have thera peutic benefits as adjuvant treatments to medications, although not for different variables or patient groups. Conclusion. In many studies, patients with chronic schizophrenia who received n-3 PUFA supplementation showed no improvement in their clinical condition.

Effects of omega-3, omega-6, and total dietary polyunsaturated fatty acid supplementation in patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis.

Background: Uncertainty exists about the link between omega-3 fatty acid, omega-6 fatty acid, and total polyunsaturated fatty acid (PUFA) intake and mortality in atherosclerotic cardiovascular disease (ASCVD) patients, and no meta-analyses summarize the relationship between these various types of PUFAs and ASCVD. Methods: Web of Science, PubMed, EBSCO and Cochrane Library up to November 30, 2022 were searched for prospective randomized controlled studies investigating the relationships among omega-3, omega-6, and PUFA intake and mortality and cardiovascular events in ASCVD patients. This study has been registered at PROSPERO (No. CRD42023407566). Results: This meta-analysis included 21 publications from 17 studies involving 40 861 participants published between 1965 and 2022. In ASCVD patients, omega-3 may lower all-cause mortality (RR: 0.90, 95% CI [0.83, 0.98], I2 = 8%), CVD mortality (RR: 0.82, 95% CI [0.73, 0.91], I2 = 34%) and CVD events (RR: 0.90, 95% CI [0.86, 0.93], I2 = 79%). Subgroup analyses showed that EPA or EPA ethyl ester supplementation reduced CVD events, while the mixture of EPA and DHA had no significant impact. Long-chain omega-3 consumption of 1.0-4.0 g per d reduced death risk by 3.5% for each 1 g per d increase. Omega-6 and PUFA had no significant effect on mortality or CVD events, with low-quality evidence and significant heterogeneity. Conclusions: omega-3 intake is associated with a reduced risk of all-cause mortality, CVD mortality, and CVD events in ASCVD patients, while omega-6 or total PUFA intake showed no significant association. Increasing the omega-3 intake by 1 g per d resulted in a 3.5% decrease in the risk of death. These findings support the recommendation of supplements with omega-3 fatty acids for the secondary prevention of ASCVD.

Role of Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with Type 2 Diabetes Mellitus

Role of Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with Type 2 Diabetes Mellitus

Trial of Tauroursodeoxycholic Acid Supplementation in Patients with Progressive MS (S16.007)

<h3>Objective:</h3> The main aim of this trial was to assess safety and tolerability of tauroursodeoxycholic acid (TUDCA) supplementation in patients with progressive multiple sclerosis (pwPMS). Secondary objectives were to assess the effects on serum BA profile and clinical outcomes. <h3>Background:</h3> We have previously identified changes in the metabolome, specifically in bile acid (BA) metabolism in MS. We demonstrated that BA receptors are present in MS lesions, and TUDCA supplementation ameliorated disease in an animal model of MS and had direct anti-inflammatory effects on astrocytes and microglia. Trials in other neurodegenerative diseases have shown that TUDCA may be neuroprotective. The effects of TUDCA supplementation on MS are unknown but could provide a pathway for developing new therapies in PMS. <h3>Design/Methods:</h3> In this randomized, double-blinded trial, pwPMS were enrolled and randomized 1:1 to either receive TUDCA (1 g twice daily) or placebo for 16 weeks. Clinical visits occurred at 0, 8, and 16 weeks. Primary outcomes were safety and tolerability of TUDCA. Secondary outcomes included changes in BA serum levels and clinical outcomes. <h3>Results:</h3> Of the 59 participants enrolled, 47 (80%) completed ≥2 visits and were included in the analysis (21 in placebo arm, 26 in TUDCA arm). The number of participants reporting adverse events was not significantly different between groups (10 in TUDCA arm vs 7 in placebo arm; p=0.72). The TUDCA group demonstrated significant increases over time in levels of TUDCA (p&lt;0.001), glycoursodeoxycholic acid (p&lt;0.001), ursodeoxycholic acid (p&lt;0.001), and lithocholic acid (p=0.02). There was a significant improvement in MSFC (p=0.03), while no change was noted in EDSS and MSQOL-54 mental or physical composites in the TUDCA arm; no significant changes were noted in these outcomes in the placebo arm. <h3>Conclusions:</h3> TUDCA supplementation was safe and tolerable in pwPMS, and led to significant increases in levels of several bioactive secondary BAs and improvement in MSFC score. <b>Disclosure:</b> The institution of Dr. Harrison has received research support from National MS Society. Dr. Ladakis has nothing to disclose. Mr. Hwang has nothing to disclose. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ad Scientiam. Dr. Sotirchos has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Sotirchos has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Sotirchos has received research support from National Institutes of Health. The institution of Dr. Sotirchos has received research support from National Multiple Sclerosis Society. The institution of Dr. Sotirchos has received research support from Sumaira Foundation. The institution of Dr. Sotirchos has received research support from Genentech. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving as a Ad Hoc Reviewer with National Institutes of Health. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Disarm Therapeutics. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Investigation. The institution of Dr. Calabresi has received research support from Biogen. The institution of Dr. Calabresi has received research support from Annexon. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME. Dr. Calabresi has a non-compensated relationship as a Consultant with Apellis that is relevant to AAN interests or activities. The institution of Dr. Bhargava has received research support from EMD Serono. The institution of Dr. Bhargava has received research support from Amylyx pharmaceuticals. The institution of Dr. Bhargava has received research support from Genentech. The institution of Dr. Bhargava has received research support from GSK.

Benefits of essential amino acid supplementation in patients following total knee arthroplasty

Benefits of essential amino acid supplementation in patients following total knee arthroplasty

Lipoic acid supplementation associated with neural epidermal growth factor-like 1 (NELL1)–associated membranous nephropathy

Lipoic acid (alpha lipoic acid, thioctic acid) is a popular over-the-counter antioxidant and insulin-mimetic supplement under investigation in a variety of conditions including multiple sclerosis, diabetes, and schizophrenia. Unfortunately, high-grade proteinuria was an unexpected adverse event specific to the treatment arm of our clinical trial investigating lipoic acid supplementation in patients with multiple sclerosis. This observation led to detection of similar patients in our nephrology practice. Here, we describe four biopsy-proven cases of neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy following lipoic acid supplementation and a fifth suspected case. Discontinuation of lipoic acid and supportive therapy resulted in remission.

Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with Lower Extremity Arterial Disease

Background Omega-3 polyunsaturated fatty acid (PUFA) supplements are used to treat lower extremity arterial disease (LEAD), but their effects on patient outcomes remain controversial. Objective We aimed to investigate the effect of omega-3 PUFA supplements on outcomes in LEAD patients. Design We systematically searched for randomized controlled trials (RCTs) published before February 2020 in PubMed, the Cochrane Library, EMBASE, Medline, and ClinicalTrials.gov. Three researchers extracted the study design, sample size, omega-3 PUFA dosage, and patient characteristics. A random-effects model was used. The primary outcomes were the mean change in the ankle-brachial index (ABI) and pain-free and maximal walking distance. The secondary outcomes were the mean changes in triglycerides and other lipid profiles, high-sensitivity C-reactive protein level, blood pressure, flow-mediated vasodilatation, and incidence of cardiovascular events. Results Sixteen RCTs and 1,852 patients were analyzed. Most of the included RCTs had a low risk of bias. The grade quality was moderate in ABI, C-reactive protein, and cardiovascular events; very low in triglyceride; and low in the other outcomes. The use of omega-3 PUFAs was not significantly associated with the primary outcomes, but it was significantly associated with a reduced triglyceride level, with a moderate effect size (Hedges' g=-0.34, 95% CI [-0.55-0.13], p < 0.01, I2=32.5%). This significant association was only found for marine-based omega-3 PUFAs. Omega-3 PUFAs and eicosapentaenoic acid dosages >2 g per day were associated with reduced levels of triglycerides. Meta-regression also showed that the use of eicosapentaenoic acid was significantly negatively associated with the triglyceride level in a dosage-dependent manner. No significant association was found in the other secondary outcomes. Conclusion This meta-analysis showed that the use of marine-based omega-3 PUFAs was significantly associated with a reduced level of triglycerides. The strength of the association depended on the dosage of eicosapentaenoic acid. (CRD42020168416 at PROSPERO.)

Long Term Efficacy and Safety of Herring Roe Oil in the Treatment of Psoriasis, a 39-week Open-label Extension Study

The effect of omega-3 poly-unsaturated fatty acid supplements in patients with Psoriasis vulgaris has previously been investigated, but interventions varied in source, composition, dose, administration route and duration of treatment. The observed beneficial effects in patients with Psoriasis vulgaris using herring roe oil (HRO) as a dietary supplement prompted the conduct of this investigation. We monitored the longer-term efficacy and safety of as oral treatment for patients with plaque psoriasis originally included with a Psoriasis Area Severity Index (PASI) 4 points. The most commonly reported adverse events in both groups were gastrointestinal in nature. No serious adverse reactions were reported.

Dose- and time-dependent increase in circulating anti-inflammatory and pro-resolving lipid mediators following eicosapentaenoic acid supplementation in patients with major depressive disorder and chronic inflammation

BackgroundEicosapentaenoic acid (EPA) supplementation is an effective treatment option in major depressive disorder (MDD) associated with chronic low-grade inflammation. EPA is the precursor of specialized pro-resolving lipid mediators (SPMs) termed resolvins (Rv), that serve important roles in the resolution of inflammation. The objective of this study was to assess the effects of different doses of EPA on plasma concentrations of EPA metabolites and SPMs in MDD patients. MethodsIn a 2-site study, 61 MDD patients with body mass index >25 kg/m2 and serum high-sensitivity C-reactive protein ≥3 μg/mL were enrolled in a 12-week randomized trial comparing EPA 1, 2, and 4 g/d to placebo. Plasma EPA (mol%) and SPMs (pg/mL) were measured in 42 study completers at baseline and at the end of treatment by liquid chromatography/mass spectrometry. ResultsPlasma EPA and SPM concentrations did not change in the placebo group during 12 weeks of treatment. Plasma EPA and EPA-derived metabolites increased significantly and dose-dependently in all EPA supplementation arms. The increase in 18-hydroxyeicosapentaenoic acid (18-HEPE), the precursor of RvE1–3, was significantly greater with the 4 g/d EPA dose than the other doses from week 4 to 12. RvE1 was undetected in all treatment groups, while RvE2 was detected in half of the subjects both at baseline and after treatment, with dose-dependent increases. RvE3 was detected only after supplementation, dose-dependently. A significant reduction in plasma arachidonic acid (AA), relative to baseline, was observed in all EPA arms. This was in contrast with an increase in AA-derived SPM lipoxin B4 (LXB4) in the 4 g/d arm. ConclusionsOur results show a robust effect of EPA 4 g/d supplementation in increasing plasma EPA and 18-HEPE levels, associated with improved conversion to RvE2–3, and LXB4 levels.

Ascorbic acid supplementation in type 2 diabetes mellitus: A protocol for systematic review and meta-analysis.

Background:Diabetes is one of the most common chronic diseases in the world. In recent years, with the continuous improvement of people's living standards and changes in dietary structure, the incidence of diabetes is gradually increasing. Studies have shown that ascorbic acid supplementation can reduce blood glucose, increase insulin synthesis and secretion, improve insulin resistance, and reduce the occurrence and development of complications of type 2 diabetes mellitus (T2DM). However, relevant studies have common problems such as the lack of large sample studies and low quality of included studies. Therefore, it is needed that we meta-analyze the clinical trials with high quality to elucidate the efficacy and safety of ascorbic acid supplementation in patients with T2DM.Methods:We will search randomized controlled trials published by PubMed, Embase, the Cochrane Library, Web of Science, and the Clinical Trials.gov website from inception to August 2020 on the effects of ascorbic acid supplementation on blood glucose, glycosylated hemoglobin, serum insulin, insulin resistance and other variables in T2DM patients with no language restrictions. The retrieval adopts the combination of medical subject headings and random words, and traces the references of the included literature to supplement the acquisition of relevant literature. Two researchers will independently screen the retrieved literature, extract the data and cross-check, and the Review Manage software V5.3.0 will be utilized for meta-analysis.Results:Our study will provide a high-quality and in-depth comprehensive analysis of the effects of ascorbic acid supplementation on blood glucose control, glycosylated hemoglobin and insulin resistance in type 2 diabetic patients.Conclusion:This systematic review and meta-analysis concerning randomized controlled trials of ascorbic acid supplementation for type 2 diabetic patients will provide a new direction and strong evidence to evaluate whether ascorbic acid supplementation is of benefit to glucose control and insulin resistance in T2DM.PROSPERO registration number:CRD 42019146826

Folic Acid Supplementation in Patients with Elevated Homocysteine Levels.

IntroductionFolic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5–5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease.MethodsA literature review of folic acid supplementation for various disease states including cardiovascular disease was conducted. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.ResultsIn this review, we discuss the biochemistry of folic acid, Hcy biosynthesis, Hcy and hydrogen sulfide bioavailability, pathogenesis of hyperhomocysteinemia and its role as a risk factor for disease, and treatment studies with folic acid supplementation in disease states.ConclusionFolic acid supplementation should be recommended to any patient who has an elevated Hcy level, and this level should be measured and treated at an early age, since folic acid is easily obtained and may likely reduce vascular disease and other deleterious pathologic processes in high-risk populations.

Effectiveness of omega-3 fatty acid supplementation in patients with Alzheimer disease: a systematic review and meta-analysis

Effectiveness of omega-3 fatty acid supplementation in patients with Alzheimer disease: a systematic review and meta-analysis

No Impact of Omega-3 Fatty Acid Supplementation on Symptoms or Hostility Among Patients With Schizophrenia.

ObjectiveThis study was aimed to explore the impact of fish oil (Omega-3 fatty acids) on hostility and psychopathology among patients with acute violent schizophrenia.MethodSixty seven acute hospitalized patients demonstrating violent behavior in the context of a schizophrenic illness, treated with antipsychotics, were randomly assigned to a supplement with either fish oil (N=32) or placebo (N=35) in a double-blind, placebo-controlled trial. Assessments were conducted at the baseline, week 4 and week 8.ResultsThe symptoms and hostility decreased after treatment for 4 and 8 weeks in both groups, with no group differences.ConclusionsThe current study did not find improvements in symptoms or hostility from the Omega-3 fatty acid supplementation in patients with schizophrenia. The implication is that Omega-3 fatty acids do not reduce psychopathology and hostility in acute patients with schizophrenia.

A Randomized, Double-blind, Placebo-controlled Clinical Study to Investigate the efficacy of Herring Roe Oil for treatment of Psoriasis.

The effect of omega-3 polyunsaturated fatty acid supplements in patients with psoriasis vulgaris has previously been investigated, but interventions varied in source, composition, dose, administration route and duration of treatment. The observed beneficial effects in patients with psoriasis vulgaris using herring roe oil as a dietary supplement prompted this investigation. This randomised, double-blind and placebo-controlled study was designed and performed to explore the efficacy and safety of herring roe oil supplementation in 64 patients with plaque psoriasis (ClinicalTrials.gov: NCT03359577). The primary end-point was comparing the change in mean Psoriasis Area Severity Index (PASI) scores in the herring roe oil treatment group and the placebo group from baseline to week 26. In the intention-to-treat population, a statistically significant improvement in the mean PASI score was observed with herring roe oil compared to placebo at 26 weeks. In the recruited patient group, the measured improvement was greatest in patients with a PASI score from 5.5–9.9 at baseline.

The effect of folic acid in patients with cardiovascular disease: A systematic review and meta-analysis.

The effectiveness of folic acid supplementation in stroke risk has been investigated, however, the available results are inconclusive and conflicting. The purpose of this systemic review and meta-analysis was to assess the effect of folic acid in patients with cardiovascular disease (CVD). By searching the PubMed, EMBASE, and Cochrane library databases, we conducted a meta-analysis to evaluate effect of folic acid supplementation in patients with CVD. All-cause mortality, cardiovascular mortality, the risk of coronary heart disease (CHD) and stroke were summarized; hazard ratios (HR), the relative risk (RR) and its 95% confidence interval (CI) were also calculated. Fixed effects models were used to combine the data. A total of 12 randomized controlled trials, which involved 47,523 participants, met the inclusion criteria in this systematic review and meta-analysis. Our meta-analysis showed that cardiovascular patients who received folic acid therapy had significantly decreased risk of stroke (RR = 0.85, 95% CI = 0.77-0.94, Pheterogeneity = .347, I = 10.6%) compared with patients who received control treatment. However, no significant difference in all-cause mortality (HR, 0.97, 95% CI, 0.86-1.10, Pheterogeneity = .315, I = 15.4%), cardiovascular mortality (HR, 0.87, 95% CI, 0.66-1.15, Pheterogeneity = .567, I = 0) and risk of CHD (RR, 1.04, 95% CI, 0.99-1.10, Pheterogeneity = .725, I = 0) were found between the 2 groups. This meta-analysis suggested that folic acid supplementation significantly reduced the risk of stroke in patients with CVD.

New Areas of Interest: Is There a Role for Omega-3 Fatty Acid Supplementation in Patients With Diabetes and Cardiovascular Disease?

Summarize studies on omega-3 fatty acids in prevention of albuminuria in subjects with diabetes. Several small, short-term trials suggested benefit on albuminuria in subjects with diabetes; however, results were not definitive. Welty et al. showed that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 1year slowed progression of early-stage albuminuria in subjects with diabetes with clinical coronary artery disease on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, the majority of whom had an albumin/creatinine ratio (ACR) < 30μg/mg. Moreover, significantly more (3-fold) subjects on EPA and DHA had a decrease in ACR compared to control, and three on EPA and DHA had a change in category from > 30μg/mg to < 30μg/mg, whereas no controls did. Potential mechanisms for benefit are discussed. These results suggest that there is benefit and perhaps even reversal of albuminuria with EPA and DHA at an early stage of disease in those with ACR < 30μg/mg and those with microalbuminuria (ACR > 30).

Oral α-lipoic acid supplementation in patients with non-alcoholic fatty liver disease: effects on adipokines and liver histology features.

Considering the importance of adipokines in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and due to the possible beneficial effects of α-lipoic acid (α-LA) on these adipose-derived hormones, this study aimed to investigate the effect of α-LA supplementation on adipokines and liver steatosis in obese patients with NAFLD. In a double-blind, placebo-controlled randomized clinical trial with two parallel groups, fifty patients with NAFLD were randomized to receive daily supplementation with either two capsules of α-LA (each capsule containing 600 mg α-LA) or two placebo capsules, daily for 12 weeks. At the baseline, all participants received consultation on how to implement a healthy diet into their daily lives. Anthropometric measures, dietary intakes, liver enzymes and adipokines were assessed at the baseline and after 12 weeks of intervention. A significant reduction was observed in the serum levels of insulin (P = 0.024) and leptin (P = 0.019) in the α-LA group compared to the placebo group, but changes in anthropometric and body composition measures, serum glucose (FSG), resistin, irisin and liver enzymes did not differ between the groups. α-LA supplementation resulted in a statistically significant elevation in the quantitative insulin sensitivity check index (QUICKI) (P = 0.033), serum levels of adiponectin (P = 0.008) and adiponectin-to-leptin ratio (P = 0.007) compared to the placebo. The liver steatosis intensity improved significantly. Nonetheless, no significant differences were observed between the study groups in the liver steatosis intensity, at the end of the study. According to the results, α-LA supplementation for 12 weeks improved insulin resistance, serum levels of insulin, adiponectin and leptin without changing anthropometric measures, serum liver enzymes, resistin and irisin.

A randomized controlled trial comparing effects of a low-energy diet with n-3 polyunsaturated fatty acid supplementation in patients with non-alcoholic fatty liver disease.

Background:Weight loss is the cornerstone of NAFLD management, but weight maintenance is difficult. Some studies have suggested that n-3 polyunsaturated fatty acid (n-3 PUFA) might have beneficial effects in NAFLD. We aim to compare the effects of a low-energy diet with n-3 PUFA supplementation on liver enzymes, body composition, and cardiometabolic risk factors in NAFLD.Materials and Methods:The study was a randomized controlled trial conducted in Urmia in Iran from October 2016 to May 2017. One hundred and fourteen eligible patients were randomly assigned to one of the three following groups: low-energy diet group, n-3 PUFA supplementation (fish oil) group (1500 mg/d), or control group for 12 weeks. Liver enzymes, lipid profile, insulin resistance, and body composition were assessed before and after the intervention.Results:One hundred and four patients completed the study. All groups lost weight, but the reductions were greater in the diet group (−2.97 ± 2.79 kg, P = 0.001). The diet group had significant decreases in fat mass compared to other groups. Insulin resistance, total cholesterol, and low-density lipoprotein cholesterol significantly decreased only in the diet group, and patients who lost weight ≥4% showed significantly larger decreases in serum liver enzymes. N-3 PUFA had no beneficial effects on the study outcomes.Conclusion:We found that 1500 mg/d n-3 PUFA supplied for 12 weeks, in contrast to 3.40 ± 2.98% weight loss, does not improve liver enzymes, body composition, and cardiometabolic risk factors in NAFLD patients.

Cerebral folate deficiency in adults: A heterogeneous potentially treatable condition

ObjectiveTo describe the phenotype and the response to folinic acid supplementation of cerebral folate deficiency (CFD) in adults, a disorder diagnosed on low 5-methyltetrahydro-folate (5MTHF) in cerebrospinal fluid (CSF), which can correspond to a inherited disorder of folate metabolism (IDFM) or to a metabolic consequence of various neurological diseases. MethodsWe conducted a retrospective study on 224 adult patients with neurological symptoms who had a 5MTHF CSF dosage, collecting their neurologic and neuroimaging data. Results69 patients had CFD (CSF 5MTHF level < 41 nmol/L), 25 of them had severe CFD (sCFD; ≤25 nmol/L) with adult onset neurological symptoms in 41%. 56% of sCFD patients had an underlying identified neurologic disorder, mainly mitochondrial diseases, hepatic encephalopathy and primary brain calcifications (no identified IDFM), the others were classified as undiagnosed. sCFD patients presented most frequently pyramidal syndrome (75%), movement disorders (56%), cerebellar syndrome (50%) and intellectual disability (46%). MRI findings mostly showed white matter abnormalities (WMA; 32%) and calcifications (12%), and were normal in 23%. The clinico-radiological phenotype of sCFD patients was not clearly different from non CFD patients in terms of manifestations frequency. However, their neurological picture was more complex with a higher number of combined neurological symptoms (4.7±1.6 vs 3.4±1.7, p = .01). In Magnetic Resonance Spectroscopy (MRS), Choline/Creatine (Cho/Cr) ratio was lower in sCFD patients (n = 7) compared to non-CFD patients (n = 73) (p = .005), with good sensitivity (71%) and excellent specificity (92%). Among twenty-one CFD patients treated with folinic acid, nine had a sustained improvement, all with sCFD but one (50% of sCFD patients improved). In two undiagnosed patients with extremely low 5MTHF CSF values, MRI WMA and low Cho/Cr ratios, folinic acid treatment leaded to a dramatic clinical and radiological improvement. ConclusionCSF 5MTHF dosage should be considered in patients with mitochondrial diseases, primary brain calcifications and unexplained complex neurological disorders especially if associated with WMA, since folinic acid supplementation in patients with sCFD is frequently efficient.

Clinical and metabolic response to flaxseed oil omega-3 fatty acids supplementation in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial

BackgroundData on the effects of flaxseed oil omega-3 fatty acids supplementation on wound healing and metabolic status in subjects with diabetic foot ulcer (DFU) are scarce. ObjectiveThis study was conducted to evaluate the effects of flaxseed oil omega-3 fatty acids supplementation on wound healing and metabolic status in subjects with DFU. MethodsThe current randomized, double-blind, placebo-controlled trial was conducted among 60 subjects (aged 40–85years old) with grade 3 DFU. Subjects were randomly allocated into two groups (30 subjects each group) to receive either 1000mg omega-3 fatty acids from flaxseed oil supplements or placebo twice a day for 12weeks. ResultsAfter the 12-week intervention, compared with the placebo, omega-3 fatty acids supplementation resulted in significant decreases in ulcer length (−2.0±2.3 vs. −1.0±1.1cm, P=0.03), width (−1.8±1.7 vs. −1.0±1.0cm, P=0.02) and depth (−0.8±0.6 vs. −0.5±0.5cm, P=0.01). Additionally, significant reductions in serum insulin concentrations (−4.4±5.5 vs. +1.4±8.3 μIU/mL, P=0.002), homeostasis model of assessment-estimated insulin resistance (−2.1±3.0 vs. +1.0±5.0, P=0.005) and HbA1c (−0.9±1.5 vs. −0.1±0.4%, P=0.01), and a significant rise in the quantitative insulin sensitivity check index (+0.01±0.01 vs. −0.005±0.02, P=0.002) were seen following supplementation with omega-3 fatty acids compared with the placebo. In addition, omega-3 fatty acids supplementation significantly decreased serum high sensitivity C-reactive protein (hs-CRP) (−25.5±31.5 vs. −8.2±18.9μg/mL, P=0.01), and significantly increased plasma total antioxidant capacity (TAC) (+83.5±111.7 vs. −73.4±195.5mmol/L, P<0.001) and glutathione (GSH) concentrations (+60.7±140.2 vs. −15.5±129.7μmol/L, P=0.03) compared with the placebo. ConclusionsOverall, omega-3 fatty acids supplementation for 12weeks among subjects with DFU had beneficial effects on parameters of ulcer size, markers of insulin metabolism, serum hs-CRP, plasma TAC and GSH levels. In addition, flaxseed oil omega-3 fatty acids may have played an indirect role in wound healing due to its effects on improved metabolic profiles.