Resveratrol and diabetes -
Resveratrol and Diabetic Retinopathy One of the more devastating pathophysiological sequelae of protracted glycaemic instability is the degradation of vision resulting from acute retinopathy.
Retinopathy is one of the leading causes of blindness among adult populations worldwide. Overexpression of the angiogenesis regulator, VEGF, has been implicated as a major promoter in the proliferation of these dysfuntional vascular structures.
Aberrant angiogenesis and macular oedema are cofactors principally responsible for the progressive loss of visual acuity, which can advance in a relatively brief time to blindness. Resveratrol is a non-invasive, multi-modal, chemo-preventative agent with the ability to prevent or impede the onset and development of diabetic retinopathy.
Resveratrol attenuates the progression of retinopathy by suppressing angiogenesis, 50,51 inhibiting inflammation 52 and downregulating neuronal apoptosis.
Safety and Tolerability of Resveratrol Resveratrol is well tolerated in both young and older humans, and does not cause any serious adverse effects in subjects on doses of up to 5 g per day. Neither have toxicity or adverse effects been observed at higher doses; however, limited data exist upon which to base any definitive conclusions relative to doses higher than 5 g per day.
It is safe as revealed by lack of serious adverse events detected by clinical, biochemical and haematological indices during intervention and a two-week follow up.
Conclusion Resveratrol has been shown to be effective in modulating blood glucose levels, decreasing insulin resistance, inhibiting chronic inflammation, improving blood lipid profiles, attenuating diabetic hypertension and countering odixative stress. Resveratrol may also play a role in the prevention or retardation of diabetes-related comorbidities and complications.
The biological processes, signalling pathways, proteomics and biochemical modalities via which resveratrol operates have been extensively investigated and are relatively well identified and defined.
The therapeutic effects of this phytoalexin appear to include a significant improvement of an array of relevant metrics including improvement of insulin sensitivity, modulation of blood glucose levels, cardiovascular protection, attenuation of diabetic hypertension, inhibition of oxidative stress and chronic inflammation, improvement of blood lipid profiles and support of retinal health.
Major challenges remain concerning the safety and efficacy of chronic resveratrol administration as well as optimal doses, due to the wellknown hormetic actions of the compound, which demonstrates protective properties at lower doses and detrimental effects at higher doses.
Furthermore, although resveratrol administration shows beneficial effects, its molecular mechanisms of action are only partially known.
However, the biological activity of these active metabolites needs to be elucidated fully. Indeed, the majority of in vitro available data have been obtained by employing the unconjugated form of resveratrol, at concentrations that largely exceed those that can be reached in vivo, at both plasma and tissue levels.
Additional clinical trials are required to better elucidate the optimum dosages, delivery mechanisms and optimally efficacious drug— resveratrol combinations, as well as the qualitative nature of the potential long-term benefits associated with this compound as a nutraceutical adjunct to existing diabetes treatment stratagems.
Given the absence of observed adverse effects attributed to this compound after more than 10 years of investigation, coupled with clinical evidence of its efficacy and safety, the use of resveratrol as a nutritional supplement is well justified in patients with type 2 diabetes.
Healthcare practitioners should be aware of the potential benefits of resveratrol as an effective adjunct nutraceutical enhancement to patients with diabetes pharmaceutical and lifestylefocused prevention and treatment stratagems.
Moola Joghee Nanjan has no conflicts of interest to declare. James Betz is an employee of Biotivia Labs LLC. James Betz, Chief Science Officer, Biotivia Labs LLC, D North Harrison St, Arlington, Virginia E: james.
betz gmail. touchREVIEWS in Endocrinology. Type 2 diabetes T2D is one of the most common chronic noncommunicable diseases, its incidence is exponentially increasing and is one of the leading causes of morbidity and mortality worldwide.
Welcome to the latest edition of touchREVIEWS in Endocrinology. In this issue we feature a range of articles to keep you up to date with the latest discussions and developments in the field of medical endocrinology.
We start with an expert interview from the Founder and CEO of the Global Liver Institute, Donna Cryer, who […]. Type 1 diabetes mellitus T1DM is an autoimmune disease secondary to the destruction of the insulin-producing β cells of the islets of the pancreas.
Environmental factors presumably trigger the disease in genetically susceptible individuals, leading to a lifetime dependency on exogenous insulin. Share this activity. Let's go! Feedback Thank you for your feedback. Back to Activity. Next question. Quick Links:.
Article Information. Overview Over the past 10 years more than 10, papers and in vitro investigations have been published that identify or analyse various critical pathways and biological processes through which the phytoalexin resveratrol has been shown to attenuate the metabolic dysfunctions, acute symptomatology and the consequential downstream pathologies related to type 2 diabetes.
Keywords Resveratrol, diabetes, diabetes management, metformin, metformin adjunct, glucose homeostasis, cardiovascular protection, adjuvant therapy. Disclosure Moola Joghee Nanjan has no conflicts of interest to declare.
Correspondence James Betz, Chief Science Officer, Biotivia Labs LLC, D North Harrison St, Arlington, Virginia com Support The publication of this article was supported by Biotivia. Received T References Akkati S, Sam KG, Tungha G, Emergence of promising therapies in diabetes mellitus, J Clin Pharmacol, ;— Hanhineva K, Torronen R, Bondia-Pons I, et al.
Philippe J, Raccah D, Treating type 2 diabetes: how safe are current therapeutic agents? Broadly, it is considered that hydroxylation of phenols increases the α-amylase inhibitory activity and methoxylation, which blocks the free hydroxyl groups and reduces the inhibitory activity [ 19 ]. Apparently, the activity is increased by more phenolic substitutions.
Piceatannol with four OH groups showed higher activity than resveratrol with three free hydroxyl groups as for the study of Zhang et al. This is further evident by the study of Lam et al.
Pentahydroxystilbene 5 OH groups showed higher inhibitory activity IC 50 Molecular docking studies have revealed that, overall, the inhibitory activity of phenols depends on two parameters: i hydrogen bonding capacity of the OH groups of the phenols with the side chains of amino acids such as Asp and Glu, and ii planarity of aromatic rings to form an efficient conjugated π-π system with the indole Trp59 of the active site [ 20 ].
and Vateria indica Linn. The compounds showed a concentration-dependent inhibition of both α-glucosidase and α-amylase enzymes. Further, the study also indicated the positive effect of hopeaphenols as antiglycating agents, with IC 50 values of The results indicated that the hopeaphenols can be a promising natural compound in diabetic management [ 21 ].
Few reports exist on the in-vivo studies of stilbenoids other than resveratrol. Among them is the effect of pterostilbene, which improves glycemic control in insulin-resistant obese rats by increasing hepatic glucokinase activity and increasing skeletal muscle glucose uptake [ 22 ].
In vitro studies also indicate that pterostilbene protected pancreatic beta cells against oxidative stress and apoptosis [ 23 ].
Antihyperglycemic properties of pterostilbene along with other phenolic constituents of Pterocarpus marsupium have been reported [ 24 , 25 ], whereas pterostilbene has been shown to be beneficial in animal models of diabetes and metabolic disorders.
Further, the study by Lam et al. Although numerous data exist on the beneficial outcomes of resveratrol in diabetic animals and in vitro , there are limited studies that have specifically investigated the antidiabetic effects of resveratrol in humans.
Further, because of not only a limited number of clinical surveys, but also limited sample size and conflicting data, the use of resveratrol as an effective antidiabetic agent has been delayed [ 27 ]. Few of the reported clinical trial data are discussed below. Glycated hemoglobin HbA1c levels reflect glycemic control and can, consequently, be employed as a predictor of the microvascular and macrovascular complications associated with type 2 diabetes.
HbA1c levels seem to be determined by postprandial hyperglycemia. The study reported improvement in HbA1c, systolic blood pressure, and total cholesterol in patients with type 2 DM treated with resveratrol combined with the oral hypoglycemic agents.
The study showed that resveratrol did not cause any changes in a glucose-dependent insulinotropic polypeptide GIP and glucagon-like peptide 1 GLP-1 levels in diabetes patients. However, they did show that resveratrol significantly decreased insulin resistance and blood glucose and delayed glucose peaks after meals.
In the study, resveratrol treatment was shown to significantly decrease HbA1c, systolic blood pressure, and total cholesterol. A decrease in oxidative stress assessed by measuring urinary ortho-tyrosine excretion, a bio marker of oxidative stress, was also reported.
Nevertheless, the authors found no evidence that resveratrol influenced homeostasis model of assessment of β-cell function HOMA-β and therefore suggested that the mechanism of antidiabetic effects might be referable to a reduction in oxidative stress and a more-efficient insulin signaling.
Resveratrol activated the Akt insulin signaling pathway by increasing the phosphoAkt:Akt ratio in platelets. Most significant notice from the above two studies is the extra security of resveratrol as compared to available standard antidiabetic medication [ 31 ].
In contrast, in a randomized control trial by Thazhath et al. The study revealed no significant improvement in glycemic control [ 32 ]. They studied two incretin hormones that affect postprandial hyperglycemia: glucose-dependent insulinotropic polypeptide GIP and glucagon-like peptide 1 GLP-1 from the bowel.
In healthy people, both hormones stimulate insulin, but in type 2 patients, only GLP-1 can act to stimulate insulin. GLP-1 can also suppress glucagon secretion and energy intake and slow gastric emptying, thereby targeting postprandial hyperglycemia.
In rodent models, resveratrol has been shown to upregulate GLP-1 and lower glycemia, but Thazhath et al.
found that in human patients, there was no difference between the GLP-1 secretion, fasting glucose level, postprandial glucose level, HbA1c, gastric emptying, body weight, or energy intake in the resveratrol-treated versus the placebo group.
Similarly, resveratrol treatment for 6 months did not improve metabolic parameters in type 2 diabetic patients [ 33 ]. Crandall et al. studied older adults with impaired glucose tolerance IGT , a major risk factor for diabetes as well as cardiovascular disease.
They establish that although fasting plasma glucose was unchanged with low dose of resveratrol treatment, peak postmeal glucose and 3-h glucose declined. Further postmeal insulin decreased and insulin sensitivity imporved.
Thus, established resveratrol as a promising therapy for insulin resistance [ 34 ]. A meta-analysis was carried out by Liu et al. in [ 35 ] and more recently by Zhu et al. in [ 36 ] with the aim of qualitatively comparing the published data on effect of resveratrol on plasma glucose levels, glycated hemoglobin HbA1c , and insulin sensitivity.
A fixed-effect model analysis was carried out to pool the data, nine studies with participants in case by study of Zhu et al. and participants of 11 eligible studies in case of Liu et al. Resveratrol was unable to reduce the plasma glucose levels at low concentrations. These studies also revealed that compared to placebo group, the patients who received resveratrol supplement also showed low insulin levels.
Further resveratrol was also effective in reducing the systolic and diastolic blood pressures. However, no significant difference was observed in LDL and HDL levels. On the other hand, effect of pterostilbene on human type 2 diabetes is yet to be researched.
Administration of blueberry Vaccinium myrtillus and sea buckthorn Hippophae rhamnoides extract for children with type 1 diabetes for 2 months elicited a reduction in HBA1c levels and an increase in SOD and glutathione peroxidase levels [ 37 ]. Since pterostilbene has been isolated from Vaccinium myrtillus [ 38 ], this effect may be ascribable to the presence of pterostilbene alongside other bioactive compounds in the excerpt.
Some beneficial effects have also been reported in resveratrol treatment in nondiabetic humans. In obese subjects, Timmers and colleagues [ 39 ] reported significant improvement in the metabolic profile and general health after resveratrol supplementation for 30 days, thereby describing resveratrol as a calorie restriction mimetic.
Resveratrol showed beneficial effects on glucose homeostasis and insulin sensitivity, reduced intrahepatic lipid IHL content and expression of inflammatory genes and improved mitochondrial efficiency. These effects may be linked with the activation of AMPK and increased SIRT1 and PGC-1α protein content in the muscle [ 39 ].
One of the major challenges surrounding the clinical utility of resveratrol is achieving its stability and adequate bioavailability at tolerable doses—a common issue in translating promising findings from cell culture and animal models into clinical efficacious drugs.
However, the data on toxicity of resveratrol in long-term experiments are scarce. Its reported oral bioavailability values range from 20 to After intravenous administration, resveratrol exhibited a very short half-life of 14 min due to rapid metabolism.
This poor bioavailability can be ascribed to the rapid conjugation of trans-resveratrol to glucuronic acid and sulfates, producing glucuronides and sulfate conjugates that accumulate in plasma and urine.
In detail, resveratrol is absorbed in a relatively high rate through the small intestine either via passive diffusion due to its nonpolar character or through active diffusion across the intestinal epithelium via cell ATP-dependent binding cassette transporters.
Inside the enterocytes of the small intestine and hepatocytes of the liver, the glucuronide and sulfate conjugation of trans-resveratrol to the major metabolites are extensive. The extensive metabolism to glucuronide and sulfate conjugates during absorption is well described and decreases circulating levels of free trans-resveratrol.
Thus, metabolism of resveratrol ultimately results in relatively small amounts of free trans-resveratrol in the plasma to be delivered to other tissues. Strategies to increase bioavailability from oral delivery of resveratrol are generally focused on increasing the rate of resveratrol absorption into the enterocytes and decreasing intracellular metabolism [ 40 ].
Further, the photostability of the resveratrol itself must also be considered when developing formulations, as resveratrol is sensitive to both heat and UV light. New approaches to increase the bioavailability of resveratrol can help to actualize its potentials as a therapeutic agent in DM and related complications.
Different approaches have been utilized by various researchers to increase the stability and bioavailability, some of which are discussed below. One simple approach to enhance bioavailability has been the consumption of resveratrol in combination with other phenolic compounds that play as the substrate for enzymes involved in resveratrol metabolism; such compounds which have demonstrated the positive effects are piperine, quercetin, etc.
Combined effect of resveratrol along with curcumins was evaluated by Rouse et al. on animal models and human islet cell lines. Beneficial effects were demonstrated on insulin secretion by these naturally occurring polyphenols.
However, the study revealed that the combination of resveratrol along with curcuminoids either did not yield any additional benefits or reduced the beneficial effects observed with the individual treatments. It would be noteworthy to test the combined effect of these two well-studied compounds on human models along with cinnamon and another known natural compound effective for diabetics.
Further, clinical data are available on co-administration of resveratrol with various food and beverage, which contain subsequent amounts of other polyphenols such as grape juice, etc.
Due to 3-hydroxyl groups, resveratrol rapidly undergoes glucuronidation or sulphation. The presence of two methoxy groups in the pterostilbene structure makes it more lipophilic and thus more bioavailable and also more metabolically stable because it has only one free hydroxyl group available for glucuronidation or sulphation.
However, the data also reveal that more the free hydrozyl groups, it shows better activity in in-vitro assays. Furthermore, administration of pterostilbene in a clinical trial at a dose of mg twice daily for 6—8 weeks was found to be safe and did not evoke any remarkable adverse reactions.
Still, there are no clinical studies on the antidiabetic effect of pterostilbene on diabetic patients and its co-treatment with resveratrol.
Another approach to increase the absorption of resveratrol in the gastrointestinal tract is improving the material properties of resveratrol used in the oral dosage, given the rapid metabolism of resveratrol.
This is the basis for SRT, the patented formulation of micronized oral version of resveratrol that may have higher bioavailability. The small particle size with the emulsifiers in solution theoretically increases surface area for intestinal absorption while also improving suspension properties [ 42 ].
Another approach to maximize the bioavailability of free trans-resveratrol is to develop resveratrol prodrugs, which could be used to improve the anti-diabetic efficacy of resveratrol.
Assuming that maximizing free trans-resveratrol is the primary goal, resveratrol prodrug generates in vivo resveratrol through enzymatic reactions. Some of these technologies have been investigated in animal studies with no report in humans.
Metabolism of prodrugs into resveratrol in tissues of interest can maximize tissue concentration and can be beneficial in the treatment of tissue specific complications in diabetic patients. Targeted delivery of resveratrol prodrugs into tissues of interest via delivery systems such as liposome-mediated delivery or nanotechnological approaches may result in the improved therapeutic effect.
Also, intravenous injection as an option to the traditional oral route of administration of resveratrol may bypass gastrointestinal absorption, conjugation, and hepatic metabolism, therefore resulting in increased bioavailability and improved results in diabetic patients.
A routine of recent surveys have concentrated on applying nanotechnology to improve the bioavailability of resveratrol and have generally demonstrated improved stability and bioavailability with minimal side effects compared to oral dosing. The nanoencapsulation methods include polylactic coglycolic acid nanoparticles [ 43 , 44 ], carboxymethyl chitosan nanoparticles [ 45 ], solid lipid nanoparticles [ 46 ], and cyclodextrin nanoparticles [ 47 ].
Studies revealed sustained release profiles, which enhanced plasma bioavailability compared to free resveratrol. Nanoencapsulation was also effective in improving the solubility and stability of resveratrol.
All the same, no clinical or paraclinical studies have been done to determine the efficacy of resveratrol nanovectors against antidiabetic potential. In vivo studies in a rat model showed prolonged plasma levels up to 16 h, in comparison with the free drug being cleared within 6 h [ 44 ].
Zu et al. developed carboxymethyl chitosan nanoparticles as a carrier for resveratrol [ 45 ]. In this system, the efficiency of the cellular uptake depended on the molecular interactions with the biological membrane organization, lipid rafts, and the actin cytoskeleton invaginations for the receptor-mediated entrance [ 48 ].
Resveratrol-loaded solid lipid nanoparticles have been also prepared by Pandita et al. This drug delivery system showed prolonged release in vitro up to h in a Wistar rat model, enhancing plasma bioavailability compared to a free drug suspension.
Finally, cyclodextrins-resveratrol complexes have been used to increase the concentration of polyphenol in aqueous solution while maintaining its biological activity. For example, spherical cyclodextrin-based nanosponges showed increasing solubility and stability, together with good drug encapsulation efficiency, compared to free resveratrol [ 48 ].
There is a large body of evidence indicating resveratrol as an antidiabetic agent. Numerous studies have demonstrated that resveratrol can prevent, attenuate, or reverse diabetic dysfunction through diverse mechanisms and multiple molecular targets, which lead to pleiotropic therapeutic action in the whole organism.
The exerted effects include inhibition of carbohydrate hydrolyzing enzymes α-amylase and α-glucosidase resulting in improved glycemic control, antioxidant properties, and antiinflammatory properties, which ultimately ameliorates diabetes and its complications. Resveratrol enhances insulin sensitivity and decreases insulin resistance, by changes in expression and activity of phosphodiesterases, kinases, AMPK, and SIRT1 in different tissues, which ultimately leads to protection of pancreatic β-cells from deterioration.
Despite widespread use of resveratrol as a nutritional supplement and the fact that animal models have provided a strong case for resveratrol as an antidiabetic agent, however, due to limited number of well-designed human clinical trials and various other limitations, this compound is still under investigation as an antidiabetic drug.
The poor stability and bioavailability of resveratrol in humans have been a major concern for translating basic science findings into clinical utility [ 49 ].
From the 11 human clinical trial data available on effect of resveratrol as antidiabetic agent, all studies have shown positive effect of resveratrol in reducing the fasting plasma glucose level at higher concentration. But still there remain many discrepancies such as on the Hb1AC levels.
The origins of these discrepancies are not definitively known but may be due to different quantification techniques e. In addition, inter-bioavailability of resveratrol can vary from person to person, which may cause inconsistent physiological responses between individuals and limited clinical applicability.
Thus, further well-defined clinical trials should exploit the efficacy of resveratrol itself or when used in combination with other antidiabetic drugs e. or with other known antidiabetic natural products curcumins, cinamaldedhye, etc.
as a potential pharmaceutical intervention. A number of approaches have been developed to improve the stability and bioavailability of resveratrol, including consumption with various foods containing multiple polyphenols and micronized powders, combining it with additional phytochemicals, controlled release devices, and nanotechnological formulations.
Animal studies demonstrate that these advanced formulations could improve tolerability in humans while also increasing its bioavailability; nonetheless, these nanotechnological and other advanced approaches are yet to be attempted in humans [ 41 ].
A combinational approach, as well as improved formulations of resveratrol, may help to overcome the challenge of maintaining an effective concentration at the site of action for an appropriate period, which needs to be confirmed by human studies.
Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Edited by Farid A. Open access peer-reviewed chapter Resveratrol in Management of Diabetes and Obesity: Clinical Applications, Bioavailability, and Nanotherapy Written By Vinitha M.
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IntechOpen Resveratrol Adding Life to Years, Not Adding Years to Lif On the other hand, small but significant reductions in blood pressure may be attributed to the improvements in glucose homeostasis and insulin resistance.
In the current work, we found no significant change in the serum lipid profiles of T2DM patients. Studies in humans and animal models suggest that resveratrol exert beneficial effects on lipids by modulating the genes involved in lipid metabolism [ 38 , 39 ].
However, an [ 28 ] included study reported a positive effect for HDL. All other studies reported insignificant effects for increased HDL levels. Decreasing trends were also observed, but no significant change was noted in the LDL levels after resveratrol supplementation. The effects of resveratrol on lipids were apparent only in obese subjects and not in subjects with low body mass index.
Resveratrol could have failed to influence metabolism because most patients were not obese. Our review features a number of strengths. This review includes all available RCTs addressing the clinical question and is the most up-to-date systematic review of the topic.
Our review also considered the dose and duration of resveratrol supplementation in T2DM patients in great detail. Nevertheless, several limitations exist in the present analysis. First, the study used the data provided by the published literature, and the data for each patient were unavailable.
Hence, test condition bias might exist. Second, some included studies were of low quality because random allocation schemes were not hidden.
Thus, the findings were unreliable. With reduced reliability, the results should be treated with caution in clinical practice. Third, the sample size of the included RCTs was so small that significant metabolic changes associated with resveratrol might not have been detected.
Another limitation is that the forms of resveratrol obviously differed. Extracts and powders may provide different bioactive compounds with varying levels of potency and bioavailability.
The differences in dose and duration might have also affected the accuracy of the results. Therefore, high-quality studies are required to determine the dose-dependent effects at varying treatment periods. This study provides novel insights into the beneficial effects of resveratrol supplementation on T2DM.
Specifically, resveratrol supplementation may improve fasting plasma glucose, HOMA-IR, and insulin in diabetic patients. This result proves that the drug may ameliorate metabolic parameters. Therefore, studies with durations longer than three months should be designed to confirm the efficacy of resveratrol and determine the appropriate dosage regimen in managing T2DM.
Most of the included articles did not explain whether adverse events occurred in the studies. The long-term risks and benefits of resveratrol supplementation are unknown.
Understanding the efficacy of resveratrol in diabetic patients requires large-scale, well-designed, and population-based studies in the future. Jeffery N, Harries LW. Beta-cell differentiation status in type 2 diabetes.
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Changes in insulin resistance in the placebo group were lacking. Effects on body weight and body mass index in both groups were lacking.
The authors concluded that resveratrol may have beneficially antidiabetic effects in people with diabetes. Additional well-designed clinical trials are necessary to further evaluate these findings.
Attention was first drawn to resveratrol in when it was mentioned as a constituent of red wine. Humans have been consuming wine for approximately 7, years. Resveratrol and other polyphenols in wine are thought to account in part for the so-called "French paradox," the finding that the rate of coronary heart disease mortality in France is lower than that observed in other industrialized countries with a similar risk factor profile.
For more information about integrative therapies for diabetes, please visit Natural Standard's Comparative Effectiveness Database. To comment on this story, please visit Natural Standard's blog.
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Print Feedback. September Resveratrol May Lower Blood Sugar Resveratrol may lower blood sugar levels in people with diabetes, according to a new study.
References Movahed A, Nabipour I, Louis XL, et al. Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients. Evidence-Based Complementary and Alternative Medicine VolumeArticle ID Natural Standard: The Authority on Integrative Medicine.
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: Resveratrol and diabetes| NatMed Pro - Resveratrol May Lower Blood Sugar | It is thought to play a role in preventing heart disease. Early studies have shown that resveratrol has antioxidant, anticancer, antifungal, antiviral, and antibacterial effects. Since resveratrol is found in grapes and wines, early research focused on linking resveratrol to the potential heart health benefits of moderate wine drinking. However, this research has expanded to examine the effects of resveratrol on many medical conditions, including cancer, bacterial and viral infections, Alzheimer's disease, and Parkinson's disease. Early research suggests that resveratrol may increase insulin sensitivity and reduce blood sugar levels in people who have diabetes. However, more research is needed before conclusions can be made. In a recent study, researchers randomly assigned 66 participants with diabetes to receive one gram of resveratrol or placebo daily for 45 days. Factors such as age, gender, bodyweight and blood pressure were similar for participants in both groups. Various outcome measures, including body weight, fasting blood glucose, insulin resistance, blood pressure, and cholesterol levels were evaluated before and after the 45 days of supplementation. The researchers found that the participants in the resveratrol group had significantly lower blood pressure, blood glucose and insulin resistance when compared to their levels at the beginning of the study. Additionally, high-density lipoprotein HDL, or "good" cholesterol significantly increased. Conversely, participants in the placebo group had moderately, but significantly, increased blood glucose and low-density lipoprotein LDL, or "bad" cholesterol levels when compared to the beginning of the study. Pharmacological research. Zare Javid A, Hormoznejad R, Yousefimanesh HA, Zakerkish M, Haghighi-Zadeh MH, Dehghan P, et al. The Impact of Resveratrol Supplementation on Blood Glucose, Insulin, Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2 Diabetic Patients with Chronic Periodontitis. Phytother Res. Liu K, Zhou R, Wang B, Mi MT. Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. Faghihzadeh F, Adibi P, Hekmatdoost A. The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Faghihzadeh F, Hekmatdoost A, Adibi P. Resveratrol and liver: A systematic review. J Res Med Sci. Marchal J, Blanc S, Epelbaum J, Aujard F, Pifferi F. Effects of chronic calorie restriction or dietary resveratrol supplementation on insulin sensitivity markers in a primate, Microcebus murinus. Chen L, Wang T, Chen G, Wang N, Gui L, Dai F, et al. Shah AD, Langenberg C, Rapsomaniki E, Denaxas S, Pujades-Rodriguez M, Gale CP, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1. Lancet Diabetes Endocrinol. Azorin-Ortuno M, Yanez-Gascon MJ, Gonzalez-Sarrias A, Larrosa M, Vallejo F, Pallares FJ, et al. Effects of long-term consumption of low doses of resveratrol on diet-induced mild hypercholesterolemia in pigs: a transcriptomic approach to disease prevention. J Nutr Biochem. Ahn J, Cho I, Kim S, Kwon D, Ha T. Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. J Hepatol. Download references. The authors would like to thank Pal Brasnyo and Silvie Timmers for providing us with additional details on their data to compute effect sizes. This study was funded by the National Natural Science Foundation of China grant number The datasets used and analyzed during the current study available from the corresponding author on reasonable request. Department of Endocrinology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, , China. You can also search for this author in PubMed Google Scholar. XYZ and LL conceived the idea for the review. XYZ drafted the article. XYZ, SHQ and XLY developed the search strategy. SHQ and LL provided input on study methodology. XYZ and CHW undertook screening and data extraction. All authors provided substantial contributions to interpretation of data, commented on draft manuscripts and have given their approval for publication. Correspondence to Ling Li. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Funnel plots of meta-analysis of the effect of resveratrol on other parameters. Forest plot of effect of resveratrol on insulin level. Forest plot of effect of resveratrol on systolic blood pressure. Forest plot of effect of resveratrol on diastolic blood pressure. Forest plot of effect of resveratrol on low-density lipoprotein cholesterol. Forest plot of effect of resveratrol on high-density lipoprotein cholesterol. ZIP kb. Risk of bias of include trials. Random sequence generation: Unclear risk of bias in 4 trails for insufficient information about the sequence generation process. Allocation concealment: Unclear risk of bias for insufficient information in 7 trails. Blinding of participants and personnel: Unclear risk of bias for insufficient information in 3 trails. Blinding of outcome assessment: Unclear risk of bias for insufficient information in 2 trails. Incomplete outcome data: High risk of bias in 3 trails for unbalanced high proportion of dropped participants. Other bias: Low risk of bias in 1 trails. TIFF kb. Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Zhu, X. et al. Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis. Nutr Metab Lond 14 , 60 Download citation. Received : 28 June Accepted : 18 September Published : 22 September Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Download ePub. Abstract Although the regular consumption of resveratrol has been known to improve glucose homeostasis and reverse insulin resistance in type 2 diabetes mellitus T2DM , the reported results are inconsistent. Background Type 2 diabetes mellitus T2DM is a long-term, multifactorial, metabolic disease with severe complications. Methods This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement [ 19 ]. Study selection Eligible studies were determined by two reviewers XYZ, CHW , and disagreement was resolved by discussion and consultation with a third reviewer SHQ. Publication bias According to Egger and colleagues, publication bias assessment is not reliable for less than 10 pooled studies [ 20 ]. Statistical analysis The primary outcomes were fasting plasma glucose, HbA1c, and HOMA-IR. Results Search results and study characteristics The initial search yielded potentially relevant articles. Full size image. Table 1 Characteristics of the 9 randomized controlled trials included in the analysis Full size table. Table 2 Baseline characteristics of the included studies Full size table. Forest plot of effect of resveratrol on fasting plasma glucose. Forest plot of effect of resveratrol on HbA1c. Forest plot of effect of resveratrol on homeostatic model assessment of insulin resistance. Discussion As revealed in this review, resveratrol supplementation for T2DM treatment resulted in significant and clinically important changes in the levels of fasting plasma glucose and insulin, HOMA-IR index, systolic blood pressure, and diastolic blood pressure. Conclusions This study provides novel insights into the beneficial effects of resveratrol supplementation on T2DM. Abbreviations BMI: Body mass index FBG: Fasting blood glucose HbA1c: Hemoglobin A1c HDL-c: High density lipoprotein cholesterol HOMA-IR: homeostasis model assessment of insulin resistance LDL-c: Low density lipoprotein cholesterol RCT: Randomized control trial. References Jeffery N, Harries LW. Article CAS Google Scholar Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Article CAS PubMed Google Scholar Martin CL, Albers JW, Pop-Busui R, Group DER. Article CAS PubMed Google Scholar Zhang P, Zhang X, Brown J, Vistisen D, Sicree R, Shaw J, et al. 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Article CAS PubMed PubMed Central Google Scholar Marchal J, Blanc S, Epelbaum J, Aujard F, Pifferi F. Article CAS PubMed PubMed Central Google Scholar Chen L, Wang T, Chen G, Wang N, Gui L, Dai F, et al. Article CAS PubMed Google Scholar Shah AD, Langenberg C, Rapsomaniki E, Denaxas S, Pujades-Rodriguez M, Gale CP, et al. Article PubMed PubMed Central Google Scholar Azorin-Ortuno M, Yanez-Gascon MJ, Gonzalez-Sarrias A, Larrosa M, Vallejo F, Pallares FJ, et al. Article CAS PubMed Google Scholar Ahn J, Cho I, Kim S, Kwon D, Ha T. DOI: The increasing prevalence, involvement of several signaling pathways, variable pathogenesis, progressive natural history and complications of type 2 diabetes emphasize an urgent need for a molecule with multiple actions. Resveratrol 3,5,4'-trihydroxy-trans-stilbene is a polyphenolic antioxidant present in red wine gaining a worldwide interest because of its multi-target effect against diabetes and other life-threatening diseases. Improving insulin sensitivity, enhancing GLUT4 translocation, reducing oxidative stress, regulating carbohydrate metabolizing enzymes, activating SIRT1 and AMPK, and decreasing adipogenic genes are some promising mechanisms established until now for resveratrol. Apart from these, resveratrol attenuates the end organ damage and reduced diabetic complications. Resveratrol exerts its beneficial antidiabetic action as evidenced from the in vitro, preclinical and clinical studies. Considering all the benefits of resveratrol in diabetes, resveratrol based different nutraceutical products have been developed commercially to use in humans. However, this compound is still under investigation because of some limitations. Resveratrol can be taken in to account in the treatment of diabetes after overcoming all hurdles and difficulties. Keywords: Clinical studies , insulin resistance , molecular mechanism , resveratrol , diabetes , sirtuins. Title: Application of Resveratrol in Diabetes: Rationale, Strategies and Challenges. Volume: 15 Issue: 4. Abstract: The increasing prevalence, involvement of several signaling pathways, variable pathogenesis, progressive natural history and complications of type 2 diabetes emphasize an urgent need for a molecule with multiple actions. Bagul P. and Banerjee S. Applied Biomathematics for Nucleic Acid Chemistry and Protein Folding: Quantitative Simulations. Molecular and Physiological Insights into Plant Stress Tolerance and Applications in Agriculture. Bagul and Drug Discovery Research Center, Translational Health Science and Technology Institute, Faridabad, India. Banerjee Volume 15, Issue 4, Page: [ - ] Pages: 19 DOI: Purchase PDF. Mark Item. Current Molecular Medicine. Title: Application of Resveratrol in Diabetes: Rationale, Strategies and Challenges Volume: 15 Issue: 4 Author s : P. |
| Application of Resveratrol in Diabetes: Rationale, Strategies and Challenges | Similarly, resveratrol treatment for 6 months did not improve metabolic parameters in type 2 diabetic patients [ 33 ]. To comment on this story, please visit Natural Standard's blog. Most significant notice from the above two studies is the extra security of resveratrol as compared to available standard antidiabetic medication [ 31 ]. Type 1 diabetes is associated with complete or relative insulin deficiency related to autoimmune-mediated destruction of pancreatic b-cells. Conclusion Resveratrol has been shown to be effective in modulating blood glucose levels, decreasing insulin resistance, inhibiting chronic inflammation, improving blood lipid profiles, attenuating diabetic hypertension and countering odixative stress. However, Movahed et al. The treatment of T1DM requires insulin replacement via injections as the pancreatic β-cells are destroyed and do not secrete adequate insulin. |
| Resveratrol supplementation may lower average blood sugar levels, study finds | Contact us Submission enquiries: emily. com customercare cbspd. Aberrant angiogenesis and macular oedema are cofactors principally responsible for the progressive loss of visual acuity, which can advance in a relatively brief time to blindness. Availability of data and materials The datasets used and analyzed during the current study available from the corresponding author on reasonable request. Bhakkiyalakshmi E, Shalini D, Sekar TV, Rajaguru P, Paulmurugan R, Ramkumar KM. Bagul P. |
| Diabetes and Resveratrol | Purchase PDF. Mark Item. Current Molecular Medicine. Title: Application of Resveratrol in Diabetes: Rationale, Strategies and Challenges Volume: 15 Issue: 4 Author s : P. Bagul and S. Banerjee Affiliation: Keywords: Clinical studies , insulin resistance , molecular mechanism , resveratrol , diabetes , sirtuins. Close Print this page. Export Options ×. Export File: RIS for EndNote, Reference Manager, ProCite. Content: Citation Only. Citation and Abstract. About this article ×. Cite this article as: Bagul P. Close About this journal. Related Journals Current Bioactive Compounds. Current Diabetes Reviews. Current Enzyme Inhibition. Current Genomics. Current Medicinal Chemistry. Current Gene Therapy. Current Topics in Medicinal Chemistry. Current Signal Transduction Therapy. Medicinal Chemistry. This information should not be interpreted as specific medical advice. Copyright © NatMed. Commercial distribution or reproduction prohibited. NatMed is the leading provider of high-quality, evidence-based, clinically-relevant information on natural medicine, dietary supplements, herbs, vitamins, minerals, functional foods, diets, complementary practices, CAM modalities, exercises and medical conditions. Monograph sections include interactions with herbs, drugs, foods and labs, contraindications, depletions, dosing, toxicology, adverse effects, pregnancy and lactation data, synonyms, safety and effectiveness. Login Subscribe. Print Feedback. September Resveratrol May Lower Blood Sugar Resveratrol may lower blood sugar levels in people with diabetes, according to a new study. References Movahed A, Nabipour I, Louis XL, et al. Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients. Evidence-Based Complementary and Alternative Medicine Volume , Article ID Natural Standard: The Authority on Integrative Medicine.  The information in this brief report is intended for informational purposes only, and is meant to help users better understand health concerns. Nanotechnological approaches to enhance the stability and bioavailability of resveratrol A routine of recent surveys have concentrated on applying nanotechnology to improve the bioavailability of resveratrol and have generally demonstrated improved stability and bioavailability with minimal side effects compared to oral dosing. References 1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for and Diabetes Research and Clinical Practice. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TPA. Indian herbs and herbal drugs used for the treatment of diabetes. 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Journal of Agricultural and Food Chemistry. Hetta MH, Aly HF, Ali NW. Estimation of resveratrol content in peanut pericarp and its relation to the in vitro inhibitory activity on carbohydrate metabolizing enzymes. Die Pharmazie. Zhang AJ, Rimando AM, Mizuno CS, Mathews ST. Alpha-glucosidase inhibitory effect of resveratrol and piceatannol. The Journal of Nutritional Biochemistry. Gonzales GB, Smagghe G, Grootaert C, Zotti M, Raes K, Camp HJV. Drug Metabolism Reviews. Xiao JB, Högger P. Dietary polyphenols and type 2 diabetes: Current insights and future perspectives. Current Medicinal Chemistry. Sasikumar P, Prabha B, Reshmitha TR, Veluthoor S, Pradeep AK, Rohit KR, et al. RSC Advances. Gómez-Zorita S, Fernández-Quintela A, Aguirre L, Macarulla MT, Rimando AM, Portillo MP. Pterostilbene improves glycaemic control in rats fed an obesogenic diet: Involvement of skeletal muscle and liver. Bhakkiyalakshmi E, Shalini D, Sekar TV, Rajaguru P, Paulmurugan R, Ramkumar KM. Therapeutic potential of pterostilbene against pancreatic beta-cell apoptosis mediated through nrf2. British Journal of Pharmacology. Manickam M, Ramanathan M, Jahromi MA, Chansouria JP, Ray AB. Antihyperglycemic activity of phenolics from pterocarpus marsupium. Journal of Natural Products. Grover JK, Vats V, Yadav SS. Pterocarpus marsupium extract vijayasar prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate. Lam SH, Chen JM, Kang CJ, Chen CH, Lee SS. α-Glucosidase inhibitors from the seeds of Syagrus romanzoffiana. Berman AY, Motechin RA, Wiesenfeld MY, Holz MK. The therapeutic potential of resveratrol: A review of clinical trials. NPJ Precision Oncology. Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutrition Research. Movahed A, Nabipour I, Lieben-Louis X, Thandapilly SJ, Yu L, Kalantarhormozi M, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evidence-Based Complementary and Alternative Medicine. Brasnyó P, Molnár GA, Mohás M. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. British Journal of Nutrition. Bashmakov YK, Assaad-Khalil SH, Abou-Seif M. Resveratrol promotes foot ulcer size reduction in type 2 diabetes patients. ISRN Endocrinology. Thazhath SS, Wu T, Bound MJ, Checklin HL, Standfield S, Jones KL, et al. Administration of resveratrol for 5 wk has no effect on glucagon-like peptide 1 secretion, gastric emptying, or glycemic control in type 2 diabetes: A randomized controlled trial. The American Journal of Clinical Nutrition. Bo S, Ponzo V, Ciccone G, Evangelista A, Saba F, Goitre I, et al. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. 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Editors-in-Chief: Andras Guttman Rrsveratrol Institute of Hair growth solutions and Process Znd University of Pannonia Veszprém Hungary. ISSN Print Ahd ISSN Online : DOI: Dlabetes increasing prevalence, involvement of several signaling pathways, variable pathogenesis, progressive natural history and complications of type 2 diabetes emphasize an urgent need for a molecule with multiple actions. Resveratrol 3,5,4'-trihydroxy-trans-stilbene is a polyphenolic antioxidant present in red wine gaining a worldwide interest because of its multi-target effect against diabetes and other life-threatening diseases.
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