This paper reviews the scientific evidence regarding the vitamin C status of people with diabetes mellitus and whether they might have increased dietary vitamin C requirements. English language articles published from 1935 to the present that either compare ascorbic acid concentrations of persons with and without diabetes mellitus or assess the impact of vitamin C supplementation on various health outcomes among persons with diabetes mellitus were examined. Most studies have found people with diabetes mellitus to have at least 30% lower circulating ascorbic acid concentrations than people without diabetes mellitus. Vitamin C supplementation had little impact on blood glucose concentrations but was found to lower cellular sorbitol concentrations and to reduce capillary fragility. Much of the past research in this area has been methodologically weak. To further understand the relation of ascorbic acid and diabetes mellitus, randomized clinical trials of ascorbic acid supplementation should be a high priority for research.
Source: Will, Julie C., and Tim Byers. “Does diabetes mellitus increase the requirement for vitamin C?.” Nutrition reviews 54.7 (1996): 193-202.
Several recent studies suggest that vitamin C (ascorbic acid [AA]) status may be altered in insulin-dependent diabetes mellitus (IDDM). We measured the AA content of mononuclear leukocytes (MM-AA) as an indicator of tissue vitamin C status in adults with IDDM and nondiabetic adults matched for age and sex. Dietary vitamin C intake and plasma AA were analyzed to ensure that vitamin C availability was adequate. Dietary vitamin C intakes were above recommendations and were not different between the groups. MN-AA was reduced by 33% on average (P < .05) in adults with IDDM (1.75 μg/mg total protein [TP]) when compared with nondiabetics (2.60 μg/mg TP). When MN-AA is indexed to the dietary vitamin C intake (), the storage deficit in adults with IDDM averages 50% (P < .05). This observation suggests an impaired tissue AA storage in adults with IDDM and supports the theory that intracellular scurvy contributes to the chronic degenerative complications of the disease.
Source: Cunningham, John J., et al. “Reduced mononuclear leukocyte ascorbic acid content in adults with insulin-dependent diabetes mellitus consuming adequate dietary vitamin C.” Metabolism 40.2 (1991): 146-149.
The cellular uptake of vitamin C (ascorbic acid, ASC) is promoted by insulin and inhibited by hyperglycemia. If a rise in plasma ASC is uncoupled from insulin replacement in insulin-dependent diabetes mellitus (IDDM) then the degree of hyperglycemia could account for “tissue scurvy” in IDDM. Leukocyte ASC is lower in IDDMs compared with nondiabetics when vitamin C consumption is adequate and our data suggest that this is a variable component of the pathophysiology of IDDM.
The complications of diabetes mellitus are believed to result from either the intracellular accumulation of sorbitol or the nonenzymatic glycoxidation of proteins or both. With respect to the abnormal cellular accumulation of sorbitol, vitamin C supplementation has been shown to be effective in several studies of adults with diabetes; the situation regarding the prevention of protein glycoxidation by supplementation is presently unclear. The roles of ASC as an aldose reductase inhibitor and a water-soluble antioxidant in body fluids are potentially very important as adjuncts to tight glycemic control in the management of diabetes. Tissue saturation and maximal physiologic function in IDDM may require supplemental vitamin C intake.
Source: Cunningham, John J. “The glucose/insulin system and vitamin C: implications in insulin-dependent diabetes mellitus.” Journal of the American College of Nutrition 17.2 (1998): 105-108.
If confirmed, our results raise the possibility that current efforts to encourage populations to consume diets rich in antioxidants, including vitamin C, could reduce the occurrence of gestational diabetes mellitus.
Source: Zhang, Cuilin, et al. “Maternal plasma ascorbic acid (vitamin C) and risk of gestational diabetes mellitus.” Epidemiology 15.5 (2004): 597-604.
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.
Source: Ali Abd El-Aal, Eman A Abd El-Ghffar, asmaa Abu Ghali, Mohammed R. Zughbur, Mahmoud M. Sirdah. “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” Diabetes & Metabolic Syndrome. (2018): 12(4):483-489.
Background: Limited data are available that evaluated the effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy (DN).
Objective: This study was conducted to evaluate the effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with DN.
Methods: This randomized double-blind placebo-controlled clinical trial was carried out among 60 patients with DN. Patients were randomly allocated into two groups to take either 1200 IU/d of vitamin E supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the onset of the study and after 12-week intervention to assess biomarkers of kidney injury, inflammation, and oxidative stress.
Results: After 12 weeks of intervention, compared with the placebo, vitamin E supplementation resulted in a significant increase in serum vitamin E levels (+42.3 ± 13.4 vs -0.8 ± 0.8 nmol/mL, P < .001) and a significant decrease in urine protein (-6.8 ± 4.3 vs -1.0 ± 8.0 mg/dL, P=.001) and protein-to-creatinine ratio (-0.2 ± 0.1 vs 0.0 ± 0.1, P < .001). In addition, a significant reduction in serum tumor necrosis factor-α (-35.4 ± 34.9 vs +5.6 ± 6.2 ng/L, P < .001), matrix metalloproteinase-2 (-556.7 ± 485.9 vs +60.4 ± 53.7 ng/mL, P < .001), matrix metalloproteinase-9 (-1461.5 ± 1456.0 vs +225.7 ± 488.2 ng/L, P < .001), malondialdehyde (-0.9 ± 0.5 vs +0.3 ± 0.4 μmol/L, P < .001), advanced glycation end products (-1832.2 ± 1941.6 vs +177.3 ± 324.1 arbitrary unit, P < .001), and insulin concentrations (-0.5 ± 2.7 vs +0.7 ± 1.0 μIU/mL, P=.03) was seen after the administration of vitamin E supplements compared with the placebo. Supplementation with vitamin E had no significant effects on other biomarkers of kidney injury, fasting plasma glucose, and insulin resistance compared with the placebo.
Conclusion: Overall, our study demonstrated that oral high-dose vitamin E supplementation for 12 weeks among DN patients had favorable effects on biomarkers of kidney injury, inflammation, and oxidative stress.
Source: Parisa Golriz Khatami, Alireza Soleimani, Nasrin Sharifi, Esmat Aghadovod, Zatollah Asemi. “The effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy: A randomized, double-blind, placebo-controlled trial” Journal of Clinical Lipidology (2016): 10(4):922-929.
Mg depletion is common in poorly controlled patients with type 2 diabetes, especially in those with neuropathy or coronary disease. More prolonged use of Mg in doses that are higher than usual is needed to establish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications.
Source: de Lourdes Lima, Maria, et al. “The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes.” Diabetes Care 21.5 (1998): 682-686.
A growing body of interest on the possible beneficial role of chromium, magnesium, and antioxidant supplements in the treatment of diabetes has contributed to debate about their value for reaching metabolic control and to prevent chronic complications in diabetic subjects. In this article we use a systematic approach focused on clinically based evidence from clinical trials regarding the benefits of chromium, magnesium, and antioxidant supplements as complementary therapies in type 2 diabetes.
Chromium, magnesium, and antioxidants are essential elements involved in the action of insulin and energetic metabolism, without serious adverse effects. However, at present there is insufficient clinically based evidence and its routine use in the treatment of type 2 diabetes is still controversial.
Because the most frequent origin of deficiencies in micronutrients is an inadequate diet, health care providers should invest more effort on nutrition counseling rather than focusing on micronutrient supplementation in order to reach metabolic control of their patients.
Results from long-term trials are needed in order to assess the safety and beneficial role of chromium, magnesium, and antioxidant supplements as complementary therapies in the management of type 2 diabetes.
Source: Guerrero-Romero, Fernando, and Martha Rodríguez-Morán. “Complementary therapies for diabetes: the case for chromium, magnesium, and antioxidants.” Archives of medical research 36.3 (2005): 250-257.
The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent (type II) diabetic patients. Nine elderly non-obese noninsulin-dependent (type II) diabetic patients, treated by diet only, participated in the study, which was designed as randomized, double-blind, and cross-over. Each patient was followed up for a pre study period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation (15.8 mmol/day) for 4 weeks. At the end of each treatment period, a euglycemic hyperinsulinemic glucose clamp with simultaneous D-[3-3H]glucose infusion and indirect calorimetry was performed. Magnesium supplementation resulted in significantly increased plasma and erythrocyte magnesium levels, whereas body weight and fasting plasma glucose did not change. In the last 60 min of the glucose clamp, insulin-mediated glucose disappearance, total body glucose disposal (24.5 +/- 0.4 vs. 28.2 +/- 0.7 mumol/kg.min; P < 0.005), and glucose oxidation (13.0 +/- 0.4 vs. 16.3 +/- 0.8 mumol/kg.min; P < 0.01) were increased after chronic magnesium supplementation. Endogenous glucose production, nonoxidative glucose disposal, lipid and protein oxidation, and insulin MCR were not affected. In conclusion, a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic-hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients. Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes.
Source: Paolisso, Giuseppe, et al. “Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly non insulin-dependent (type II) diabetic patients.” The Journal of Clinical Endocrinology & Metabolism 78.6 (1994): 1510-1514.
The aim of this review was to elaborate a synthesis about the discussions on magnesium and diabetes mellitus, in the last 14 years. The magnesium deficiency has been associated with chronic diseases, amongst them, diabetes mellitus. Epidemiological studies had shown low levels of magnesium ingestion in the general population, as well as a relation between the ingestion of food rich in magnesium and the reduction of diabetes installation and its complications. Hypomagnesemia is frequently present in diabetic patients, however, there is not an exact elucidation of the mechanism of magnesium deficiency in diabetes mellitus. On the other hand, in the presence of this illness, it is observed that inadequate metabolic control can affect the corporal concentrations of magnesium, developing hypomagnesemia, which may be still directly related with some micro and macrovascular complications observed in diabetes, like cardiovascular disease, retinopathy, and neuropathy. This way, the chronic complications of diabetes can appear precociously. Based on this, the supplementation with magnesium has been suggested in patients with diabetes mellitus who have proven hypomagnesemia and the presence of its complications.
Source: Sales, Cristiane Hermes, and Lucia de Fatima Campos Pedrosa. “Magnesium and diabetes mellitus: their relation.” Clinical nutrition 25.4 (2006): 554-562.
Magnesium is the fourth most abundant cation in the body and plays an important physiological role in many of its functions. It plays a fundamental role as a cofactor in various enzymatic reactions involving energy metabolism. Magnesium is a cofactor of various enzymes in carbohydrate oxidation and plays an important role in glucose transporting mechanism of the cell membrane. It is also involved in insulin secretion, binding, and activity. Magnesium deficiency and hypomagnesemia can result from a wide variety of causes, including deficient magnesium intake, gastrointestinal, and renal losses. Chronic magnesium deficiency has been associated with the development of insulin resistance. The present review discusses the implications of magnesium deficiency in type 2 diabetes.
Source: Chaudhary, Dharam P., Rajeshwar Sharma, and Devi D. Bansal. “Implications of magnesium deficiency in type 2 diabetes: a review.” Biological trace element research 134.2 (2010): 119-129.
These results suggest that the chromium picolinate/biotin combination, administered as an adjuvant to current prescription anti‐diabetic medication, can improve glycaemic control in overweight to obese individuals with type 2 diabetes; especially those patients with poor glycaemic control on oral therapy. Copyright © 2007 John Wiley & Sons, Ltd.
Source: Albarracin, Cesar A., et al. “Chromium picolinate and biotin combination improve glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes.” Diabetes/metabolism research and reviews 24.1 (2008): 41-51.
This pilot study demonstrates that supplementation with a combination of chromium picolinate and biotin in poorly controlled patients with diabetes receiving antidiabetic therapy improved glucose management and several lipid measurements. Chromium picolinate/ biotin supplementation may represent an effective adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism.
Source: McCarty, M. F. “High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes.” Medical Hypotheses 52.5 (1999): 401-406.
The number of people with diabetes and pre-diabetes are exponentially increasing. Studies on humans have shown the beneficial effects of Zinc supplementation in patients with diabetes. The present study aims to systematically evaluate the literature and meta-analyze the effects of Zinc supplementation on diabetes. A systematic review of published studies reporting the effects of Zinc supplementations on diabetes mellitus was undertaken. The literature search was conducted in the following databases; PubMed, Web of Science and SciVerse Scopus. A meta-analysis of studies examining the effects of Zinc supplementation on clinical and biochemical parameters in patients with diabetes was performed. The total number of articles included in the present review is 25, which included 3 studies on type-1 diabetes and 22 studies on type-2 diabetes. There were 12 studies comparing the effects of Zinc supplementation on fasting blood glucose in patients with type-2 diabetes. The pooled mean difference in fasting blood glucose between Zinc supplemented and placebo groups was 18.13mg/dl (95%CI:33.85,2.41; p < 0.05). 2-h post-prandial blood sugar also shows a similar distinct reduction in (34.87mg/dl [95%CI:75.44; 5.69]) the Zinc treated group. The reduction in HbA1c was 0.54% (95%CI:0.86;0.21) in the Zinc treated group. There were 8 studies comparing the effects of Zinc supplementation on lipid parameters in patients with type-2 diabetes. The pooled mean difference for total cholesterol between Zinc supplemented and placebo groups was 32.37mg/dl (95%CI:57.39,7.35; p < 0.05). Low-density lipoprotein cholesterol also showed a similar distinct reduction in the Zinc treated group, the pooled mean difference from random effects analysis was 11.19mg/dl (95%CI:21.14,1.25; p < 0.05). Studies have also shown a significant reduction in systolic and diastolic blood pressures after Zinc supplementation. This first comprehensive systematic review and meta-analysis on the effects of Zinc supplementation in patients with diabetes demonstrates that Zinc supplementation has beneficial effects on glycaemic control and promotes healthy lipid parameters. Further studies are required to identify the exact biological mechanisms responsible for these results.
Source: R. Jayawardena, P. Ranasinghe, P. Galappatthy, R.L.D.K. Malkanthi, G.R.Constantine, P. Katulanda. “Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis” Diabetology & Metabolic Syndrome (2012): 4:13.
Zinc deficiency is known to be associated with insulin resistance in obese individuals. This study was performed to evaluate the effect of zinc supplementation on insulin resistance and metabolic risk factors in obese Korean women. Forty obese women (body mass index (BMI) ≥ 25 kg/m2) aged 19-28 years were recruited for this study. Twenty women of the study group took 30 mg/day of supplemental zinc as zinc gluconate for 8 weeks and 20 women of control group took placebo. Usual dietary zinc intake was estimated from 3-day diet records. Insulin resistances were measured using Homeostasis model assessment (HOMA) indices, and insulin sensitivities Matsuda indices, which were calculated using oral glucose tolerance test data. Metabolic risk factors, such as waist circumference, blood pressure, fasting glucose, triglyceride, high density lipoprotein (HDL) cholesterol, and adipocyte hormones such as leptin, and adiponectin were also measured. At the beginning of study, dietary zinc averaged 7.31 mg/day and serum zinc averaged 12.98 µmol/L in the study group. Zinc supplementation increased serum zinc by 15% and urinary zinc by 56% (P < 0.05). HOMA values tended to decrease and insulin sensitivity increased slightly in the study group, but not significantly so. BMI, waist circumference, blood pressure, blood glucose, triglyceride, HDL cholesterol, and adipocyte hormones did not change in either the study or control group. These results suggest that zinc status may not affect insulin resistance and metabolic risk factors in obese Korean women. Further research is required on a larger cohort with a longer follow-up to determine the effects of zinc status on insulin resistance and metabolic variables.
Source: Jihye Kim, Sunju Lee “Effect of zinc supplementation on insulin resistance and metabolic risk factors in obese Korean women” Nutrition Research and Practice (2012) Jun; 6(3): 221–225.
Type 2 diabetes is frequently associated with both extracellular and intracellular magnesium (Mg) deficits. A chronic latent Mg deficit or an overt clinical hypomagnesemia is common in patients with type 2 diabetes, especially in those with poorly controlled glycemic profiles. Insulin and glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose-uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, postreceptorial impairment in insulin action and worsening of insulin resistance in diabetic patients. A low Mg intake and an increased Mg urinary loss appear the most important mechanisms that may favor Mg depletion in patients with type 2 diabetes. Low dietary Mg intake has been related to the development of type 2 diabetes and metabolic syndrome. Benefits of Mg supplementation on metabolic profiles in diabetic patients have been found in most, but not all clinical studies and larger prospective studies are needed to support the potential role of dietary Mg supplementation as a possible public health strategy in diabetes risk. The aim of this review is to revise current evidence on the mechanisms of Mg deficiency in diabetes and on the possible role of Mg supplementation in the prevention and management of the disease.
Source: Mario Barbagallo, Ligia J. Dominguez. “Magnesium and type 2 diabetes” World Journal of Diabetes (2015): 6(10): 1152–1157.
Chromium is an essential element which has been shown to have beneficial effects on carbohydrate and lipid metabolism. Often, dietary intake is suboptimal, and nutritional supplements may not be effective due to poor absorption in the gastrointestinal tract. A novel chromium-histidine complex has been prepared which significantly improves absorption capability over current available chromium nutritional supplements. The complex is safe, easily prepared and may be combined with an ingestible carrier for consumption as a tablet, capsule, aqueous solution, food or food product.
Source: Anderson, Richard A., Marilyn M. Polansky, and Noella A. Bryden. “Chromium-histidine complexes as nutrient supplements.” U.S. Patent No. 6,689,383. 10 Feb. 2004.
Recent reports provide cogent evidence that the average individual becomes chromium deficient with age. Unfortunately, chromium deficiency is strongly associated with many aspects of Metabolic Syndrome, including insulin resistance and type 2 diabetes. Since replacement of chromium, per os, often ameliorates many deleterious manifestations associated with insulin resistance and diabetes, it is not surprising that many different, commercial trivalent chromium compounds are available on the market. However, previous reports have shown that the form of trivalent chromium (negative charges) can influence effectiveness markedly. We compared various commercial forms of trivalent chromium commonly used alone or in formulations, to examine whether they are equally effective and non-toxic. In the first study, five different chromium products were examined – citrate, amino acid chelate (AAC), chelavite, polynicotinate (NBC), and nicotinate. In the second study, the effects of NBC and picolinate were assessed. Results demonstrated that only chelavite and NBC improved insulin sensitivity, and only NBC decreased systolic blood pressure (SBP) significantly. In the second study, both picolinate and NBC significantly decreased SBP compared to control. NBC and picolinate decreased malondialdehyde concentrations (free radical formation) and DNA fragmentation in hepatic and renal tissues. No evidence of adverse effects was noted with any of the compounds tested. In conclusion, while all the trivalent chromium compounds tested seem safe, only three enhanced insulin sensitivity (NBC, chelavite, and picolinate) and only two decreased SBP significantly (NBC and picolinate). Furthermore, both NBC and picolinate were protective in lessening free radical formation and DNA damage in the liver and kidneys.
Source: Preuss, Harry G., et al. “Comparing metabolic effects of six different commercial trivalent chromium compounds.” Journal of inorganic biochemistry 102.11 (2008): 1986-1990.
The trivalent state of chromium (Cr3+) is encountered in biological milieus and is responsible for its nutritional activity. The principal route by which trivalent chromium enters the body is the digestive system. Chromium in foods is present both in the inorganic form and as organic complexes. Intestinal absorption of chromium is low (0.5–2%), and the mechanism has not yet been fully elucidated. Absorbed chromium circulates as free Cr3+, as Cr3+ bound to transferrin or other plasma proteins, or as complexes, such as glucose tolerance factor (GTF)-Cr. Circulating trivalent chromium can be taken up by tissues, and its distribution in the body depends on the species, age, and chemical form. It is excreted primarily in the urine by glomerular filtration or bound to a low-mol-wt organic transporter. Chromium metabolism is still imperfectly understood. The use of of51Cr has nevertheless furnished valuable data concerning its transport and excretion.
Source: Ducros, Véronique. “Chromium metabolism.” Biological trace element research 32.1-3 (1992): 65-77.
The unifying hypothesis of diabetes maintains that reactive oxygen species (ROS) generated in the mitochondria of glucose-treated cells promote reactions leading to the development of diabetic complications. Although the unifying hypothesis attributes the generation of oxidants solely to impaired glucose and fatty acid metabolism, diabetes is also associated with a decline in the levels of the endogenous antioxidant taurine in a number of tissues, raising the possibility that changes in taurine status might also contribute to the severity of oxidant-mediated damage. There is overwhelming evidence that taurine blocks toxicity caused by oxidative stress, but the mechanism underlying the antioxidant activity remains unclear. One established antioxidant action of taurine is the detoxification of hypochlorous acid. However, not all of the antioxidant actions of taurine are related to hypochlorous acid because they are detected in isolated cell systems lacking neutrophils. There are a few studies showing that taurine either modulates the antioxidant defenses or blocks the actions of the oxidants, but other studies oppose this interpretation. Although taurine is incapable of directly scavenging the classic ROS, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, there are numerous studies suggesting that it is an effective inhibitor of ROS generation. The present review introduces a novel antioxidant hypothesis, which takes into consideration the presence of taurine-conjugated tRNAs in the mitochondria. Because tRNA conjugation is required for normal translation of mitochondrial-encoded proteins, taurine deficiency reduces the expression of these respiratory chain components. As a result, flux through the electron transport chain decreases. The dysfunctional respiratory chain accumulates electron donors, which divert electrons from the respiratory chain to oxygen, forming superoxide anion in the process. Restoration of taurine levels increases the levels of conjugated tRNA, restores respiratory chain activity, and increases the synthesis of ATP at the expense of superoxide anion production. The importance of this and other actions of taurine in diabetes is discussed.
Source: Schaffer, Stephen W., Junichi Azuma, and Mahmood Mozaffari. “Role of antioxidant activity of taurine in diabetes.” Canadian Journal of physiology and pharmacology 87.2 (2009): 91-99.
In this study, plasma and platelet taurine content and fluxes were determined in 38 types 2 diabetic patients and in 26 healthy control subjects. Taurine levels in diabetic patients were significantly lower than in control subjects both in plasma (32.1 v 48.6 μmol/L, P = .000) and platelets (148 v 183 nmol/mg protein, P = .043). Platelet taurine uptake in diabetic patients was significantly reduced (321.2 v 524.9 pmol total taurine 108 platelet−1 min−20, P = .000), whereas taurine release increased in comparison to healthy controls (38.7 v 29.5% of platelet 3H taurine at the start of incubation, P = .000). These results may reflect modified systems of taurine carriers or a compensatory mechanism in response to an increase of other organic osmolytes.
Source: De Luca, G., et al. “Taurine and osmoregulation: platelet taurine content, uptake, and release in type 2 diabetic patients.” Metabolism-Clinical and Experimental 50.1 (2001): 60-64.
3-Hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable as ligands for vanadyl ions, in potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use and have undergone extensive pre-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in the bone. These bis-ligand oxovanadium (IV) (VOL2) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a range of doses from 10 mg to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects; all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020), 20 mg, daily for 28 days, per os, in seven type 2 diabetic subjects, was associated with reductions in fasting blood glucose and %HbA1c; improved responses to oral glucose tolerance testing, versus the observed worsening of diabetic symptoms in the two placebo controls.
Source: Thompson, Katherine H., et al. “Vanadium treatment of type 2 diabetes: a view to the future.” Journal of inorganic biochemistry 103.4 (2009): 554-558.
Common (Cinnamomum verum, C. zeylanicum) and cassia (C. aromaticum) cinnamon have a long history of use as spices and flavoring agents. A number of pharmacological and clinical effects have been observed with their use. The objective of this study was to systematically review the scientific literature for preclinical and clinical evidence of safety, efficacy, and pharmacological activity of common and cassia cinnamon. Using the principles of evidence-based practice, we searched 9 electronic databases and compiled data according to the grade of evidence found. One pharmacological study on antioxidant activity and 7 clinical studies on various medical conditions were reported in the scientific literature including type 2 diabetes (3), Helicobacter pylori infection (1), activation of olfactory cortex of the brain (1), oral candidiasis in HIV (1), and chronic salmonellosis (1). Two of 3 randomized clinical trials on type 2 diabetes provided strong scientific evidence that cassia cinnamon demonstrates a therapeutic effect in reducing fasting blood glucose by 10.3%–29%; the third clinical trial did not observe this effect. Cassia cinnamon, however, did not have an effect at lowering glycosylated hemoglobin (HbA1c). One randomized clinical trial reported that cassia cinnamon lowered total cholesterol, low-density lipoprotein cholesterol, and triglycerides; the other 2 trials, however, did not observe this effect. There was good scientific evidence that a species of cinnamon was not effective at eradicating H. pylori infection. Common cinnamon showed weak to very weak evidence of efficacy in treating oral candidiasis in HIV patients and chronic salmonellosis.
Source: Dugoua, Jean-Jacques, et al. “From type 2 diabetes to antioxidant activity: a systematic review of the safety and efficacy of common and cassia cinnamon bark.” Canadian Journal of physiology and pharmacology 85.9 (2007): 837-847.
Inhibition of α-glucosidase and pancreatic α-amylase is one of the therapeutic approaches for delaying carbohydrate digestion, resulting in reduced postprandial glucose. The aim of this study was to evaluate the phytochemical analysis and the inhibitory effect of various cinnamon bark species against intestinal α-glucosidase and pancreatic α-amylase. The results showed that the content of total phenolic, flavonoid, and condensed tannin ranged from 0.17 to 0.21 g gallic acid equivalent/g extract, from 48.85 to 65.52 mg quercetin equivalent/g extract, and from 0.12 to 0.15 g catechin equivalent/g extract, respectively. The HPLC fingerprints of each cinnamon species were established. Among cinnamon species, Thai cinnamon extract was the most potent inhibitor against the intestinal maltase with the IC50 values of 0.58 ± 0.01 mg/ml. The findings also showed that Ceylon cinnamon was the most effective intestinal sucrase and pancreatic α-amylase inhibitor with the IC50 values of 0.42 ± 0.02 and 1.23 ± 0.02 mg/ml, respectively. In addition, cinnamon extracts produced additive inhibition against intestinal α-glucosidase and pancreatic α-amylase when combined with acarbose. These results suggest that cinnamon bark extracts may be potentially useful for the control of postprandial glucose in diabetic patients through inhibition of intestinal α-glucosidase and pancreatic α-amylase.
Source: Adisakwattana, Sirichai, et al. “Inhibitory activity of cinnamon bark species and their combination effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase.” Plant Foods for Human Nutrition 66.2 (2011): 143-148.
Objectives: To evaluate short- and long-term effects of Cinnamomum zeylanicum on food consumption, body weight, glycemic control, and lipids in healthy and diabetes-induced rats.
Materials and Methods: The study was conducted in two phases (Phase I and Phase II), using Sprague-Dawley rats in four groups. Phase I evaluated acute effects on fasting blood glucose (FBG) (Groups 1 and 2) and on post-oral glucose (Groups 3 and 4) blood glucose. Groups 1 and 3 received distilled-water and Groups 2 and 4 received cinnamon-extracts. Phase II evaluated effects on food consumption, body weight, blood glucose, and lipids over 1 month. Group A (n = 8, distilled-water) and Group B (n = 8, cinnamon-extracts) were healthy rats, while Group C (n = 5, distilled-water) and Group D (n = 5, cinnamon-extracts) were diabetes-induced rats. Serum lipid profile and HbA1c were measured on D-0 and D-30. FBG, 2-h post-prandial blood glucose, body weight, and food consumption were measured on every fifth day.
Results: Phase I: There was no significant difference in serial blood glucose values in cinnamon-treated group from time 0 (P > 0.05). Following oral glucose, the cinnamon group demonstrated a faster decline in blood glucose compared to controls (P < 0.05). Phase II: Between D0 and D30, the difference in food consumption was shown only in diabetes-induced rats (P < 0.001). Similarly, the significant difference following cinnamon-extracts in FBG and 2-h post-prandial blood glucose from D0 to D30 was shown only in diabetes-induced rats. In cinnamon-extracts administered groups, total and LDL cholesterol levels were lower on D30 in both healthy and diabetes-induced animals (P < 0.001).
Conclusions: C. zeylanicum lowered blood glucose, reduced food intake, and improved lipid parameters in diabetes-induced rats.
Source: Priyanga Ranasinghe, Sanja Perera, Mangala Gunatilake, Eranga Abeywardene, Nuwan Gunapala, Sirmimal Premakumara, Kamal Perera, Dilani Lokuhetty, Prasad Katulanda. “Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model” Pharmacognosy Research (2012): 4(2): 73–79.
This study was performed to investigate the effects of licorice on the non‐alcoholic fatty liver disease (NAFLD). In this double-blind randomized clinical trial, 66 patients were divided into case and control groups. All patients had elevated liver enzymes and had increased liver echogenicity (lipid accumulation) on sonography. The case group was treated with one capsule containing 2 g aqueous licorice root extract per day for 2 months while the control group was treated in the same manner with a placebo. Weight, body mass index (BMI) and liver transaminase levels were measured for each patient before and after the study. In the case group, the mean alanine aminotransferase (ALT) level decreased from 64.09 to 51.27 IU/mL and the aspartate aminotransferase (AST) level decreased from 58.18 to 49.45 IU/mL, which were statistically significant (p < 0.001 and p < 0.001). But in the control group, a drop in the ALT and AST levels was not statistically significant. The BMI difference before and after the study was not statistically significant in both groups. Despite the significant drop in liver enzymes following administration of licorice root extract, it is recommended that further studies that include histological examination are necessary. Copyright © 2012 John Wiley & Sons, Ltd.
Source: Hajiaghamohammadi, Ali Akbar, Amir Ziaee, and Rasoul Samimi. “The efficacy of licorice root extract in decreasing transaminase activities in non‐alcoholic fatty liver disease: A randomized controlled clinical trial.” Phytotherapy Research 26.9 (2012): 1381-1384.
Berberine has been shown to regulate glucose and lipid metabolism in vitro and in vivo. This pilot study was to determine the efficacy and safety of berberine in the treatment of type 2 diabetic patients. In study A, 36 adults with newly diagnosed type 2 diabetes were randomly assigned to treatment with berberine or metformin (0.5 g t.i.d.) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (HbA1c; from 9.5% ± 0.5% to 7.5% ± 0.4%, P < 0.01), fasting blood glucose (FBG; from 10.6 ± 0.9 mmol/L to 6.9 ± 0.5 mmol/L, P < 0.01), postprandial blood glucose (PBG; from 19.8 ± 1.7 to 11.1 ± 0.9 mmol/L, P < 0.01) and plasma triglycerides (from 1.13 ± 0.13 mmol/L to 0.89 ± 0.03 mmol/L, P < 0.05) were observed in the berberine group. In study B, 48 adults with poorly controlled type 2 diabetes were treated supplemented with berberine in a 3-month trial. Berberine acted by lowering FBG and PBG from one week to the end of the trial. HbA1c decreased from 8.1% ± 0.2% to 7.3% ± 0.3% (P < 0.001). Fasting plasma insulin and HOMA-IR were reduced by 28.1% and 44.7% (P < 0.001), respectively. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were decreased significantly as well. During the trial, 20 (34.5%) patients suffered from transient gastrointestinal adverse effects. Functional liver or kidney damages were not observed for all patients. In conclusion, this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism.
Source: Jun Yin, Huili Xing, Jianping Ye. “Efficacy of Berberine in Patients with Type 2 Diabetes” Metabolism (2008): 57(5): 712-717.
Berberine, is an alkaloid from Hydrastis canadensis L., Chinese herb Huanglian, and many other plants. It is widely used in traditional Chinese medicine as an antimicrobial in the treatment of dysentery and infectious diarrhea. This manuscript describes cardiovascular effects of berberine and its derivatives, tetrahydroberberine and 8‐oxoberberine. Berberine has positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. Both derivatives of berberine have antiarrhythmic activity. Some of the cardiovascular effects of berberine and its derivatives are attributed to the blockade of K+ channels (delayed rectifier and KATP) and stimulation of Na+‐Ca2+ exchanger. Berberine has been shown to prolong the duration of ventricular action potential. Its vasodilator activity has been attributed to multiple cellular mechanisms. The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.
Source: Lau, Chi‐Wai, et al. "Cardiovascular actions of berberine." Cardiovascular drug reviews 19.3 (2001): 234-244.
Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-inflammation, yet the exact mechanism is unknown. Because cyclooxygenase-2 (COX-2) plays a key role in prostaglandins (PGs) synthesis, which is elevated in inflammation, we examined whether the anti-inflammatory mechanism of berberine is mediated through COX-2 regulation. In oral cancer cell line OC2 and KB cells, a 12 h berberine treatment (1, 10, and 100 μM) reduced prostaglandin E2 (PGE2) production dose-dependently with or without 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 nM) induction. This berberine induced effect occurred rapidly (3 h) as a result of reduced COX-2 protein, but not enzyme activity. The electrophoretic mobility shift assay revealed that activator protein 1 (AP-1) binding was decreased in oral cancer cells treated with berberine for 2 h. Further analysis showed that berberine inhibited AP-1 binding directly. These anti-inflammatory effects paralleled the in vivo results where berberine pretreatment of Wistar rats inhibited the production of exudates and PGE2 in carrageenan induced air pouches.
Source: Kuo, Chi-Li, Chin-Wen Chi, and Tsung-Yun Liu. "The anti-inflammatory potential of berberine in vitro and in vivo." Cancer letters 203.2 (2004): 127-137.
Berberine has been shown to regulate glucose and lipid metabolism in vitro and in vivo. This pilot study was to determine the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus patients. In study A, 36 adults with newly diagnosed type 2 diabetes mellitus were randomly assigned to treatment with berberine or metformin (0.5 g 3 times a day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (from 9.5% ± 0.5% to 7.5% ± 0.4%, P < .01), fasting blood glucose (from 10.6 ± 0.9 mmol/L to 6.9 ± 0.5 mmol/L, P < .01), postprandial blood glucose (from 19.8 ± 1.7 to 11.1 ± 0.9 mmol/L, P < .01), and plasma triglycerides (from 1.13 ± 0.13 to 0.89 ± 0.03 mmol/L, P < .05) were observed in the berberine group. In study B, 48 adults with poorly controlled type 2 diabetes mellitus were treated supplemented with berberine in a 3-month trial. Berberine acted by lowering fasting blood glucose and postprandial blood glucose from 1 week to the end of the trial. Hemoglobin A1c decreased from 8.1% ± 0.2% to 7.3% ± 0.3% (P < .001). Fasting plasma insulin and homeostasis model assessment of insulin resistance index were reduced by 28.1% and 44.7% (P < .001), respectively. Total cholesterol and low-density lipoprotein cholesterol were decreased significantly as well. During the trial, 20 (34.5%) patients experienced transient gastrointestinal adverse effects. Functional liver or kidney damages were not observed for all patients. In conclusion, this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism.
Source: Yin, Jun, Huili Xing, and Jianping Ye. "Efficacy of berberine in patients with type 2 diabetes mellitus." Metabolism 57.5 (2008): 712-717.
Chili peppers exhibit antiobesity, anticancer, antidiabetic, and pain- and itch-relieving effects on animals and humans; these effects are due to capsaicin, which is the main pungent and biologically active component of pepper. Capsiate, a nonpungent capsaicin analogue, is similar to capsaicin in terms of structure and biological activity. In this study, we investigated whether capsaicin and capsiate exhibit the same hypoglycemic effects on rats with type 1 diabetes (T1D). Experimental rats were categorized into four groups: control, model, capsaicin, and capsiate groups. The two treatment groups were treated orally with 6 mg/kg bw capsaicin and capsiate daily for 28 days. Treatment with capsaicin and capsiate increased body weight, increased glycogen content, and inhibited intestinal absorption of sugar in T1D rats. Particularly, insulin levels were increased from 14.9 ± 0.76 mIU/L (model group) to 22.4 ± 1.39 mIU/L (capsaicin group), but the capsiate group (16.7 ± 0.79 mIU/L) was increased by only 12.2%. Analysis of the related genes suggested that the transient receptor potential vanilloid 1 (TRPV1) receptor was activated by capsaicin. Liver X receptor and pancreatic duodenum homeobox 1 controlled the glycometabolism balance by regulating the expression levels of glucose kinase, glucose transport protein 2 (GLUT2), phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase, leading to reduced blood glucose levels in T1D rats. Meanwhile, the hypoglycemic effect was enhanced by the down-regulated expression of sodium glucose cotransporter 1, GLUT2, and GLUT5 in the intestine. The results showed that the spicy characteristics of capsaicin might be the root of its ability to decrease blood glucose.
Source: Shiqi Zhang, Xiaohan Ma, Lei Zhang, Hui Sun, Xion Liu. “Capsaicin Reduces Blood Glucose by Increasing Insulin Levels and Glycogen Content Better than Capsiate in Streptozotocin-Induced Diabetic Rats” Journal of Agricultural and Food Chemistry (2017) Mar 22;65(11):2323-2330.
Ethnopharmacological relevance: Bitter melon (Momordica charantia L.) has been widely used as an traditional medicine treatment for diabetic patients in Asia. In vitro and animal studies suggested its hypoglycemic activity, but limited human studies are available to support its use.
Aim of study: This study was conducted to assess the efficacy and safety of three doses of bitter melon compared with metformin.
Materials and methods: This is a 4-week, multicenter, randomized, double-blind, active-control trial. Patients were randomized into 4 groups to receive bitter melon 500 mg/day, 1000 mg/day, and 2000 mg/day or metformin 1000 mg/day. All patients were followed for 4 weeks.
Results: There was a significant decline in fructosamine at week 4 of the metformin group (−16.8; 95% CI, −31.2, −2.4 μmol/L) and the bitter melon 2000 mg/day group (−10.2; 95% CI, −19.1, −1.3 μmol/L). Bitter melon 500 and 1000 mg/day did not significantly decrease fructosamine levels (−3.5; 95% CI −11.7, 4.6 and −10.3; 95% CI −22.7, 2.2 μmol/L, respectively).
Conclusions: Bitter melon had a modest hypoglycemic effect and significantly reduced fructosamine levels from baseline among patients with type 2 diabetes who received 2000 mg/day. However, the hypoglycemic effect of bitter melon was less than metformin 1000 mg/day.
Source: Anjana Fuangchan, Paveen Sonthisombat, Tippawadee Seubnukarn, Rapeepan Chanouan, Pont Chotchaisuwat, Viruch Sirigulsatien, Kornkanoklngkaninan, Pinyupa Plianbangchang, Stuart Haines. “Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients” Journal of Ethnopharmacology (2011): Vol 134, Issue 2: 422-428.
Extracts of M.charantia demonstrated antimicrobial activity on tested microorganisms except on Proteus mirabilis and Cryptococcus neoformans. Fruit extracts showed higher antimicrobial activity than leaf extract. Further studies are recommended that will involve various parts of the plant, select different fractions of extracts and purify the active antimicrobial components.
Source: Mwambete, K. D. “The in vitro antimicrobial activity of fruit and leaf crude extracts of Momordica charantia: A Tanzania medicinal plant.” African health sciences 9.1 (2009): 34-39.
Even if total cholesterol and HDL-C were significantly reduced, the clinical magnitude of this remains obscure. More and larger studies are needed to establish the effects and safety of Guggul-based formulations in the treatment for hypercholesterolemia.
Source: Nohr, Lise Anett, Lars Bjørn Rasmussen, and Jørund Straand. “Resin from the mukul myrrh tree, guggul, can it be used for treating hypercholesterolemia? A randomized, controlled study.” Complementary therapies in medicine 17.1 (2009): 16-22.
In this study, the effects of long-term nitrogen deficiency (N 0.1 mM for 4 months) on growth, phenolic content and activity of phenylalanine ammonia lyase (PAL; EC 22.214.171.124) were investigated in the leaves, inflorescences and roots of yarrow (Achillea collina Becker ex Rchb.) grown in hydroponics. The antioxidant capacity of methanol extracts was also evaluated. Nitrogen starvation decreased plant growth and the leaves’ total nitrogen, amino acids, proteins, chlorophylls and carotenoids contents indicating that the primary metabolism was severely limited by low nitrogen availability. The amount of total phenolics and the antioxidant capacity were higher in leaves and roots of nitrogen-starved compared to control plants. The most abundant phenolic acids identified in yarrow were 5-O-caffeoylquinic acid (chlorogenic acid), and 3,5 and 4,5-di-O-caffeoylquinic acids. Nitrogen starvation significantly increased the contents of all these compounds and the PAL activity in leaf and root tissues. Results suggest that hydroponics, with proper manipulation of nutritional factors, might be a suitable system for the production of compounds with health benefits, such as caffeic acid derivatives, in yarrow.
Source: Giorgi, Annamaria, et al. "Effect of nitrogen starvation on the phenolic metabolism and antioxidant properties of yarrow (Achillea collina Becker ex Rchb.)." Food Chemistry 114.1 (2009): 204-211.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia caused by defective insulin secretion, resistance to insulin action, or a combination of both. DM has reached epidemic proportions in the US and more recently worldwide. The morbidity and mortality associated with diabetes are anticipated to account for a substantial proportion of health care expenditures. Although there are several drug treatments currently available, the need for new herbal agents for the treatment of diabetes is required. The treatment goals for patients with diabetes have evolved significantly over the last 80 years, from preventing imminent mortality, to alleviate symptoms, to the now recognized objective of normalization or near normalization of glucose levels with the intent of forestalling diabetic complications. The present review stated several findings from an extensive literature search of natural plants that have been assessed for the antidiabetic activity over the past 80 years. An attempt has been made to summarize the information in order to highlight those chemical entities and plant species which are of worth for further investigation as leads to the drug developments. Over 100 plant species from a wide range of families containing various chemical classes of compounds have been cited here which are worthy for the researchers and the industrialist concerned with diabetes.
Source: Samad, Abdus, et al. “Status of herbal medicines in the treatment of diabetes: a review.” Current diabetes reviews 5.2 (2009): 102-111.