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Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials.
Rawat, D, Roy, A, Maitra, S, Gulati, A, Khanna, P, Baidya, DK
Diabetes & metabolic syndrome. 2021;(6):102324
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Abstract
BACKGROUND AND AIMS Vitamin C has been used as an anti-oxidant in various diseases including viral illnesses like coronavirus disease (COVID-19). METHODS Meta-analysis of randomized controlled trials (RCT) investigating the role of vitamin C supplementation in COVID-19 was carried out. RESULTS Total 6 RCTs including n = 572 patients were included. Vitamin C treatment didn't reduce mortality (RR 0.73, 95% CI 0.42 to 1.27; I2 = 0%; P = 0.27), ICU length of stay [SMD 0.29, 95% CI -0.05 to 0.63; I2 = 0%; P = 0.09), hospital length of stay (SMD -0.23, 95% CI -1.04 to 0.58; I2 = 92%; P = 0.57) and need for invasive mechanical ventilation (Risk Ratio 0.93, 95% CI 0.61 to 1.44; I2 = 0%; P = 0.76). Further sub-group analysis based on severity of illness (severe vs. non-severe), route of administration (IV vs. oral) and dose (high vs. low) failed to show any observable benefits. CONCLUSION No significant benefit noted with vitamin C administration in COVID-19. Well-designed RCTs with standardized control group needed on this aspect.
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The Role of Vitamin C in Two Distinct Physiological States: Physical Activity and Sleep.
Otocka-Kmiecik, A, Król, A
Nutrients. 2020;(12)
Abstract
This paper is a literature overview of the complex relationship between vitamin C and two opposing physiological states, physical activity and sleep. The evidence suggests a clinically important bidirectional association between these two phenomena mediated by different physiological mechanisms. With this in mind, and knowing that both states share a connection with oxidative stress, we discuss the existing body of evidence to answer the question of whether vitamin C supplementation can be beneficial in the context of sleep health and key aspects of physical activity, such as performance, metabolic changes, and antioxidant function. We analyze the effect of ascorbic acid on the main sleep components, sleep duration and quality, focusing on the most common disorders: insomnia, obstructive sleep apnea, and restless legs syndrome. Deeper understanding of those interactions has implications for both public health and clinical practice.
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Effects of the Lysulin™ supplementation on pre-diabetes: A randomized double-blind, placebo-controlled clinical trial.
Ranasinghe, P, Jayawardena, R, Chandrasena, L
Diabetes & metabolic syndrome. 2020;(5):1479-1486
Abstract
BACKGROUND AND AIMS Diabetes is a leading cause of morbidity and mortality worldwide. Recent studies have demonstrated that nutraceutical products have beneficial effects in diabetes. Present study aims to investigate whether a product (Lysulin™) containing amino acid lysine, micronutrient zinc and vitamin C will have beneficial effects in pre-diabetes. METHODS A randomized, double-blind, placebo-controlled trial was conducted for a period of 6 months. The two parallel groups (1:1) were Lysulin™ (Interventional group-IG) and placebo (control group-CG). Evaluations were done at baseline, 1, 3 and 6 months. Primary outcome was defined as change in glycaemic control measured by HbA1c from baseline. Other outcomes included change in; fasting plasma glucose (FPG), 2-h OGTT plasma glucose and lipid profile from baseline. Three multiple regression analyses were performed, where change in FPG, 2-h OGTT, and HbA1c post intervention from baseline respectively were the continuous dependent variable with other independent variables. RESULTS One hundred and ten participants were recruited, 50% (n = 55) were males and mean age (±SD) was 46.7 ± 9.9 years. A significantly higher percentage of participants in CG (25.4%, n = 14) developed diabetes in comparison to IG (7.3%, n = 4) (p = 0.018). FPG, 2-h OGTT and HbA1c significantly reduced in the IG only. Both total cholesterol and LDL cholesterol decreased significantly from baseline only in the IG. In all three regression models the best predictor of respective dependent variable was Lysulin™ treatment. CONCLUSIONS Lysulin™ improved glycaemic control, with reduced progression to diabetes, in those with pre-diabetes. Treatment also showed a beneficial reduction in total and LDL cholesterol levels. TRIAL REGISTRATION Sri Lanka Clinical Trials Registry, identifier: SLCTR/2018/022 (http://slctr.lk/trials/1290). Registered on 13th July 2018; Study protocol version 2.0 (23rd March 2018).
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Decreased Nuclear Ascorbate Accumulation Accompanied with Altered Genomic Methylation Pattern in Fibroblasts from Arterial Tortuosity Syndrome Patients.
Németh, CE, Nemoda, Z, Lőw, P, Szabó, P, Horváth, EZ, Willaert, A, Boel, A, Callewaert, BL, Coucke, PJ, Colombi, M, et al
Oxidative medicine and cellular longevity. 2019;:8156592
Abstract
Ascorbate requiring Fe2+/2-oxoglutarate-dependent dioxygenases located in the nucleoplasm have been shown to participate in epigenetic regulation of gene expression via histone and DNA demethylation. Transport of dehydroascorbic acid is impaired in the endomembranes of fibroblasts from arterial tortuosity syndrome (ATS) patients, due to the mutation in the gene coding for glucose transporter GLUT10. We hypothesized that altered nuclear ascorbate concentration might be present in ATS fibroblasts, affecting dioxygenase activity and DNA demethylation. Therefore, our aim was to characterize the subcellular distribution of vitamin C, the global and site-specific changes in 5-methylcytosine and 5-hydroxymethylcytosine levels, and the effect of ascorbate supplementation in control and ATS fibroblast cultures. Diminished nuclear accumulation of ascorbate was found in ATS fibroblasts upon ascorbate or dehydroascorbic acid addition. Analyzing DNA samples of cultured fibroblasts from controls and ATS patients, a lower global 5-hydroxymethylcytosine level was found in ATS fibroblasts, which could not be significantly modified by ascorbate addition. Investigation of the (hydroxy)methylation status of specific regions in six candidate genes related to ascorbate metabolism and function showed that ascorbate addition could stimulate hydroxymethylation and active DNA demethylation at the PPAR-γ gene region in control fibroblasts only. The altered DNA hydroxymethylation patterns in patient cells both at the global level and at specific gene regions accompanied with decreased nuclear accumulation of ascorbate suggests the epigenetic role of vitamin C in the pathomechanism of ATS. The present findings represent the first example for the role of vitamin C transport in epigenetic regulation suggesting that ATS is a compartmentalization disease.
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The effect of vitamin C and/or E supplementations on type 2 diabetic adult males under metformin treatment: A single-blinded randomized controlled clinical trial.
El-Aal, AA, El-Ghffar, EAA, Ghali, AA, Zughbur, MR, Sirdah, MM
Diabetes & metabolic syndrome. 2018;(4):483-489
Abstract
BACKGROUND AND AIM Recently, there has been an increasing interest in the influence of antioxidant vitamins on the efficacy of oral hypoglycemic therapy in type 2 diabetic patients (T2DM). This single-blinded randomized controlled clinical trial aimed to investigate the effect of vitamin C and/or E supplementation on the efficacy of oral hypoglycemic therapy in T2DM Palestinian male patients from the Gaza Strip. METHODS Forty T2DM male patients aged 40-60 years on metformin treatment were randomly divided into four groups, each group received an additional one of the following daily oral supplements for 90 days: placebo; vitamin C; vitamin E and vitamin C plus vitamin E. After overnight fasting, venous blood specimens were collected from all individuals into K3-EDTA tubes and serum tubes for measuring the biochemical and hematological parameters of the study at baseline and after 90 days of vitamins supplementation. RESULTS The results revealed that vitamin C and/or E improve fasting blood sugar (FBS), HbA1c, lipid profile, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), reduced glutathione (GSH); and Quantitative Insulin Sensitivity Check Index (QISCI) compared with diabetic patients group that received placebo. CONCLUSION This study provided additional evidence on the beneficial effects of supplementing antioxidant vitamins in T2DM which could improve the clinical condition and attenuate or prevent diabetic pathogenesis and complications that, secondly to poor glycemic control, could attribute to the imbalance between the decline in the endogenous antioxidants and increasing production of the reactive oxygen species leading to the oxidant-mediated damage present in the diabetic context.
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Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion.
Limberg, JK, Kellawan, JM, Harrell, JW, Johansson, RE, Eldridge, MW, Proctor, LT, Sebranek, JJ, Schrage, WG
American journal of physiology. Heart and circulatory physiology. 2014;(6):H840-7
Abstract
We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = -0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA.
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[Estimation of plasma vitamin A, C and E levels in patients with metabolic syndrome].
Godala, M, Materek-Kuśmierkiewicz, I, Moczulski, D, Rutkowski, M, Szatko, F, Gaszyńska, E, Kowalski, J
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2014;(215):320-3
Abstract
UNLABELLED Metabolic syndrome (MS) is a coexistence of metabolic risk factors affecting development of cardiovascular diseases. In the pathogenesis of MS there participate reactive oxygen species which are excessively produced in such elements of MS as hyperglycemia, insulin resistance and obesity. Vitamins A, C and E are an important part of the non-enzymatic antioxidative barrier in humans. The aim of the study was to estimate plasma vitamin A, C and E levels in patients with symptoms of MS. MATERIAL AND METHODS The study included 68 patients with symptoms of MS according to International Diabetes Federation criteria (2005), 37 men and 31 women, aged 34-65 years (mean age 57, 76 +/- 8, 29 years). The control group consisted of 24 healthy individuals without MS, 18 men and 6 women, aged 49-67 (mean age 58, 5 +/- 5, 6 years). Plasma vitamin A, C and E levels were estimated in patients and the control group with spectrophotometry using T60V spectrophotometer (PG Instruments). RESULTS The plasma vitamin A, C and E levels were significantly lower (p < 0.05) in MS patients than in the healthy individuals without symptoms of MS. The most significant differences in the level of antioxidative vitamins in both groups were related to vitamin C and vitamin E. CONCLUSIONS The decreased level of vitamins A, C and E points to the weakening of antioxidative barrier in patients with MS.
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A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia.
Bentsen, H, Osnes, K, Refsum, H, Solberg, DK, Bøhmer, T
Translational psychiatry. 2013;(12):e335
Abstract
Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18-39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day⁻¹ and active or placebo vitamin E 364 mg day⁻¹+vitamin C 1000 mg day⁻¹ (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen's d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.
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Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: Effect of ascorbic acid.
Cangemi, R, Angelico, F, Loffredo, L, Del Ben, M, Pignatelli, P, Martini, A, Violi, F
Free radical biology & medicine. 2007;(5):853-9
Abstract
Arterial dysfunction is a hallmark of early atherosclerosis; however, its behavior in patients with metabolic syndrome (MS) is still unclear. We investigated the role of oxidative stress on ischemia-induced flow-mediated dilatation (FMD) in patients with MS. FMD and oxidative stress, as assessed by serum levels of 8-hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), were studied in 18 MS and 30 control subjects. Thereafter, in the 18 MS patients, FMD was assessed after iv infusion of 1 g vitamin C or placebo in a randomized, double-blind, crossover design; serial blood samples were taken in peripheral circulation before and after FMD to analyze 8-OHdG. Compared to controls, MS patients had higher 8-OHdG (p<0.001) and lower FMD (p<0.001); 8-OHdG and FMD were inversely correlated (R=-0.74; p<0.01). In MS patients, placebo administration did not change FMD, whereas vitamin C significantly enhanced it (p<0.001). After placebo, ischemia-induced FMD was associated with a significant increase in 8-OHdG (p<0.001), an effect that was counteracted by vitamin C. Vitamin C infusion was associated with an inverse correlation between the changes in FMD and oxidative stress (R=-0.67; p<0.01). The present study shows that arterial dilatation is impaired and that enhanced oxidative stress may play a key role in patients with MS.