In vitro and in vivo reduction of erythrocyte sorbitol by ascorbic acid (original) (raw)
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Diabetes, Obesity and Metabolism
The primary aim of this study was to investigate whether ascorbic acid (AA) supplementation improves postprandial glucose responses under free-living conditions in individuals with type 2 diabetes. A secondary aim was to investigate the effect of AA supplementation on blood pressure. Materials and methods: A total of 31 individuals with type 2 diabetes (26 males and 5 females; aged 61.8 AE 6.8 years; duration of diabetes, 5.6 AE 4.6 years; HbA1c, 7.6% AE 0.7% [mean AE SD]) were enrolled in a randomized cross-over study involving 4 months of supplementation with oral AA (2 × 500 mg/d) or placebo. Participants wore continuous glucose monitors for 48 hours and consumed standardized meals pre-and post-supplementation. Measurements included postprandial glucose incremental areas under the curve (iAUC), duration of day in hyper-and hypo-glycaemia status, average 24-hour and daily postprandial glucose concentrations, HbA1c, insulin, blood pressure (BP) and oxidative stress (F 2-isoprostanes). Results: Following AA supplementation, significant decreases were observed in daily postprandial glucose iAUC (−36%), in duration of day with hyperglycaemia (−2.8 h/d) and postprandial hyperglycaemia (−1.7 h/d), in average 24-hour glucose (−0.8 mmol/L) and daily postprandial glucose (−1.1 mmol/L) concentrations, in systolic (−7 mm Hg) and diastolic (−5 mm Hg) blood pressures and in a specific fraction of free plasma F 2-isoprostanes (−47 pg/mL) as compared to placebo. Conclusions: Individuals with type 2 diabetes experienced improved postprandial and 24-hour glycaemia and decreased BP after 4 months of AA supplementation as compared to placebo. These findings offer evidence for the proposed use of AA as an adjunct therapy to improve glycaemic and BP control in individuals with type 2 diabetes.
Inhibition of protein glycation and advanced glycation end products by ascorbic acid
AFRICAN JOURNAL OF BIOTECHNOLOGY, 2012
Advanced glycation end products (AGEs) formation is increased in diabetes mellitus, leading to microvascular and macrovascular complications. Recently, much attention has been focused on natural and synthetic inhibitors to delay the onset or progression of diabetes and its comorbidities. Ascorbic acid (AA) can react with proteins, including hemoglobin and possibly interfere with protein glycation process. An in vitro glycation model containing plasma from type 2 diabetic and non-diabetic healthy volunteers together with glucose as glycating agent was used to study antiglycation activity of AA. Samples with different concentrations of glucose and AA were incubated for five weeks at 37°C. Nonenzymatic glycation (NEG) was quantitated by thiobarbituric acid calorimetry and AGEs were measured by enzyme linked immuno-sorbent assay (ELISA). The NEG and AGEs levels were reduced by AA. Increasing the AA concentrations greatly diminished protein glycations, indicating dose-dependent effects of AA. Plasma NEG and AGEs were decreased with an average of 20 to 26% (p < 0.05) and 26 to 28% (p < 0.05). A significant correlation was found between the glycation inhibition and the inhibition of AGE formation (p < 0.05). The antiglycation role of AA is evident in the present study and it also indicates the possibility of inexpensive, relatively non-toxic vitamin therapy for the prevention and treatment of diabetic complications. It is plausible that AGEs inhibition by AA may also form the basis for future intervention strategies in both diabetic and non-diabetic individuals.
Journal of Cellular Biochemistry, 2002
In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P < 0.01), D þ ALA, and D þ AA6P groups (P < 0.001). Malonaldehyde (MA) level increased in diabetes (P < 0.05), D þ FO, and D þ COM groups (P < 0.001), but its level in D þ AA6P and D þ ALA groups was lower in diabetes group (P < 0.01). Total lipid level in diabetes and diabetes plus antioxidant administered groups were higher than control. Total cholesterol level was high in diabetes and D þ ALA groups (P < 0.05), but its level reduced in D þ FO compared to control and diabetes groups, P < 0.05, < 0.001, respectively. Total triglyceride (TTG) level was high in the D þ ALA (P < 0.05) and D þ COM (P < 0.001) groups. In contrast, TTG level in blood of diabetes group was higher than diabetes plus antioxidant and FO administered groups (P < 0.001). According to gas chromatography analysis results, while the palmitic acid raised in diabetes group (P < 0.05), stearic acid in D þ FO, D þ ALA, and diabetes groups was lower than control (P < 0.05), oleic acid reduced in D þ COM and D þ FO groups, but its level raised in D þ AA6P and D þ ALA groups (P < 0.01). As the linoleic acid (LA) elevated in ALA þ D, D þ AA6P, and diabetes groups, linolenic acid level in diabetes, D þ AA6P, and D þ FO groups was lower than control (P < 0.001). Arachidonic acid (AA) decreased in D þ ALA, D þ AA6P, and diabetes groups (P < 0.01), but its level in D þ COM and D þ FO was higher than control (P < 0.05). Docosahexaenoic acid (DHA) increased in D þ AA6P and D þ COM (P < 0.05). While the total saturated fatty acid level raised in diabetes group, its level reduced in D þ ALA and D þ FO groups (P < 0.05). In contrast, total unsaturated fatty acid level in D þ ALA and D þ FO groups was higher than control (P < 0.05). In conclusion, present data have confirmed that the combination of the ALA, AA6P, and FO have improvement effects on the recycling of GSSG to reduced GSH in erythrocytes of diabetic rats, and in addition to this, oxidative stress was suppressed by ALA and AA6P, and unsaturated fatty acid degree was raised by the effects of ALA and FO.
Nutritional Supplements and Their Effect on Glucose Control
Current Diabetes Reports, 2011
Type 2 diabetes is a growing health concern. The use of nutritional supplements by patients with type 2 diabetes is estimated at somewhere between 8% to 49%. The objective of this review was to search the scientific literature for advances in the treatment and prevention of type 2 diabetes with nutritional supplements. Twelve databases were searched with a focus on extracting studies published in the past 3 years. The following nutritional supplements were identified as potentially beneficial for type 2 diabetes treatment or prevention: vitamins C and E, α-lipoic acid, melatonin, red mold, emodin from Aloe vera and Rheum officinale, astragalus, and cassia cinnamon. Beta-carotene was shown to be ineffective in the prevention of type 2 diabetes. Ranging from preclinical to clinical, there is evidence that nutritional supplements may be beneficial in the treatment or prevention of type 2 diabetes. Health providers should investigate drug-nutritional supplement interactions prior to treatment.
Ascorbic acid metabolism in diabetes mellitus
Metabolism, 1981
In contrast to normal subjects diabetic patients had very low plasma ascorbic acid and significantly high (p < 0.001) dehydroascorbic acid irrespective of age. sex, duration of the disease, type of treatment. and glycemic control. However, there was no significant difference between the mean leukocyte ascorbate concentrations of the two populations. The in vitro rates of dehydroascorbate reduction in the hemolysate and the erythrocyte reduced glutathione levels and the glucose-6-phosphate dehydrogenase activities, which regulate the dehydroascorbate reduction, were similar in normal and diabetic subjects. The turnover of ascorbic acid was higher in the diabetics than that in the normal volunteers. Experiments with diabetic rats indicated that the increased turnover of ascorbic acid was probably due to increased oxidation of ascorbate to dehydroascorbete in tissue mitochondria. Ascorbic acid supplementation at a dose of 500 mg per day for a brief period of 15 days resulted in an increase in the plasma ascorbate level temporarily, but it did not lower the blood glucose level of the diabetic patients.
Diabetologia, 1991
Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1+19.3 vs 55.6 _+ 20.0, p < 0.01, vs 82.9 _+ 30.9 gmol/1, p < 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87+0.46 vs 0.61 + 0.26, p < 0.01, vs 0.38 + 0.14, p < 0.001). At three weeks, ascorbate concentrations rose in all groups (p < 0.0001) and was maintained in control subjects (151.5 + 56.3 ~tmol/1), but fell in both diabetic groups by six weeks (p<0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p < 0.0001) but rose again in the diabetic groups by six weeks (p < 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p < 0.05). No significant changes were observed in fructosamine concentrations in any group during the study. Diabetes mellitus is associated with a major disturbance of ascorbic acid metabolism which is only partially corrected by ascorbate supplementation.
Cellular Nutrition and Nutritional Medicine in Diabetes and Related Complications: An Overview
Diabetes is a chronic condition of impaired glucose cycle that alters the whole metabolism leading to high blood glucose level. Diabetes occurs when the pancreatic beta cells are either unable to produce enough insulin, or the body cells were unable to use available insulin effectively. Insulin, a storage hormone produced in the pancreatic beta cells, helps to absorb glucose for the production of energy during cellular respiration. Thus, failure of absorbing glucose by body cells results in the accumulation of glucose in the blood, which is termed as hyperglycemia. Excess blood glucose causes serious damage to the major organ systems, leading to the heart disease, kidney failure (nephropathy), blindness (retinopathy), loss of sensation in the feet and hands and even an early death. Thus, diabetes is a chronic condition where the body's ability to convert food into energy is impaired. Prevalence of diabetes along with dyslipidaemia is increasing at an explosive rate throughout the globe. Though the exact cause is unknown, many factors are believed to play roles in this pathogenesis. Genetic predispositions, faulty dietary patterns, and sedentary life-styles are the key factors for the increased prevalence of type 2 diabetes. This progressive disease develops through many years, and pre-diabetic condition is known to be reversible. Though antidiabetic drugs are the first line of defence to control blood glucose level, conventional therapy is unable to cure it, nor can prevent the long term damage of the vital systems, but needs to be used lifelong. On the other hand, the benefit of nutritional medicine and dietary supplementation in diabetes is less explored scientifically. Therefore, the safer alternatives to prevent, or minimize the long term damage and control of diabetes need a combination of healthy eating, regular physical activity, monitoring of blood glucose level, dietary control and nutritional medicine. This review will cover not only the different aspects of diabetes, but also the role of complementary personalized therapy using nutrition and nutritional medicine in its management, highlighting a proper blend of conventional therapy with nutraceuticals, for effective diabetes management.
CATRINA , 2015
Ginger and alpha-lipoic acid have recently gained attention as a potent antioxidant. The purpose of the present study was to investigate the possible therapeutic effects of daily oral administration of ginger and alpha-lipoic acid on diabetic rats. 42 Male albino rats (150-180gm) were divided into 7 groups; control, olive oil (vehicle) control, alloxan induced diabetic (DM), ginger-treated (GN), alpha-lipoic acid-treated (ALA), diabetic rats treated with ginger (DM+GN) and diabetic rats treated with alpha-lipoic acid (DM+ALA). After 5 weeks of GN and ALA administration (50 and 30 mg/kg b. wt respectively), hematological, biochemical and histological parameters were investigated. Diabetic rats exhibited a significant decrease in erythrocytic parameters as well as significant increase of fasting blood sugar (FBS), glycated hemoglobin (HbA1c), total cholesterol (TCh), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and a decrease in the level of high density lipoprotein (HDL). In addition, diabetic rats showed a significant decrease in hepatic GSH and an increase in the content of malondialdehyde (MDA). The administration of GN and ALA caused a significant decrease in FBS, HbA1c, TCh, TG, and LDL-cholesterol, concomitant with a significant increase in HDL-cholesterol was recorded. Moreover, GN and ALA administration blunted the increase in MDA and stimulated the GSH production in the liver of diabetic rats. The findings of this study indicated that injection of GN and ALA corrected the erythrocytic parameters, lipid profile, blood sugar level in diabetic rats and showed antioxidative properties. Additionally, the therapeutic effect of GN and ALA was confirmed with histopathological examination of pancreas. It could be postulated that; (i) GN and ALA have protective and anti-hyperglycemic effects and (ii) overall anti-diabetic effects of ALA are better than those of GN, at least in this experimental condition.
Ascorbic and Dehydroascorbic Acid-Connections to Type 1 Diabetes
The etiology of Type 1 diabetes (T1D) is unknown. While especially Band D-vitamins have been to some extent studied in relation to development of Type 1 diabetes, Vitamin C has been ignored despite its important effects as an antioxidant protecting against oxidative stress, its influence on the immune function including autoimmunity, and the possible direct effects on the pancreatic beta cells. Recently the demonstration of increased dehydroascorbic acid before the development of autoantibodies in serum of children with genetic risk for T1D has drawn some attention to the ascorbic and dehydroascorbic acids, which decades ago have been linked to effects on the pancreatic beta cells. As long as there is no safe, efficacious and practical way of preventing Type 1 diabetes there are reasons to resume the interest for vitamins, including Vitamin C.