By Clipper F. Young, PharmD, MPH, CDCES, BC-ADM, BCGP, APh, and Matthew Wai, DO
Dr. Young is an Associate Professor, Touro University California, College of Osteopathic Medicine, Vallejo.
Dr. Wai is a graduate of Touro University California, College of Osteopathic Medicine; Residency Training at Riverside Community Health/University of California Riverside.
In Part 1 of this literature review (appearing in the Aug. 15, 2021, issue of Internal Medicine Alert), we discussed Aloe vera and alpha-lipoic acid in detail. In this part, in-depth discussions on chromium, cinnamon, fenugreek, garlic, and Gymnema sylvestre are presented. These complementary and alternative medicine supplements include botanical and nonbotanical products for managing type 2 diabetes.
Chromium
Trivalent chromium, or chromium(III), is a trace element required for normal glucose metabolism. The benefits of chromium on blood glucose management have been linked to its potentiation of insulin action by increasing insulin sensitivity and improving glucose tolerance.1
Studies suggest chromium is a critical cofactor for insulin and important in preventing the development of diabetes mellitus in rare chromium deficiency situations.1 The results of a 2014 meta-analysis of 25 randomized controlled trials with chromium monotherapy and combined supplementation suggested improved glycemic control, especially with chromium supplementation doses of more than 200 μg daily.2 A 2016 meta-analysis revealed chromium supplementation significantly and positively lowered fasting plasma glucose levels and led to an overall decline of ≥ 0.5% in hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes.3 However, the reported trials featured high heterogeneity between treatment groups, study duration, forms of treatment, and analysis methods. Other studies failed to demonstrate any significant effects of chromium supplementation.4,5 Some randomized, clinical trials addressed adverse events with chromium supplementation, which included skin rash, constipation, and other gastrointestinal symptoms.4,5
Although higher chromium doses have been studied, 200 μg per day is the typical dose.6 Overall, the information presented is mixed in determining chromium’s efficacy in managing type 2 diabetes. The American Diabetes Association expressed no conclusive evidence supporting the use of chromium supplementation in diabetes.7
Cinnamon
Cinnamon is a preparation of the dried bark of specific evergreen trees. The proposed mechanism for diabetes use is the active ingredient, hydroxychalcone, which works as an insulin mimetic and increases insulin sensitivity by improving glucose uptake.8 Certain studies have indicated some efficacy regarding reducing fasting serum glucose up to 29% when cinnamon is consumed daily.9 The amount of cinnamon consumed in the studies ranged from 1 g to 6 g, showing modest improvement in fasting serum glucose.9 However, a 2008 meta-analysis based on five prospective, randomized, controlled trials refuted the efficacy claims of cinnamon in decreasing HbA1c and fasting plasma glucose.10 The authors of this meta-analysis concluded patients with type 1 or type 2 diabetes receiving cinnamon ranging from 1 g to 6 g did not demonstrate statistically or clinically significant changes in the endpoints compared to subjects receiving a placebo.10
In 2013, another meta-analysis included 10 randomized, controlled trials with 543 patients using cinnamon doses of 120 mg per day to 6 g per day for four to 18 weeks.11 There was a significant reduction in fasting plasma glucose (-24.59 mg/dL, 95% CI, -40.52 to -8.67 mg/dL) but no statistically significant reduction in HbA1c.11
Cinnamon’s role in patients with diabetes remains unknown. The conflicting available evidence includes a few studies with high heterogeneity where double-blinded procedures may not have been sufficient. Also, the amount of cinnamon used in studies varied widely; certain authors used amounts equivalent to about a half-teaspoon.
Fenugreek
Fenugreek is a common herb and condiment used in cooking. The purported mechanisms of its benefits in diabetes management include delaying gastric emptying, delaying carbohydrate absorption, and increasing peripheral glucose use.12 Pooled results of a meta-analysis showed fenugreek significantly reduced fasting glucose values, two-hour postprandial glucose levels, and HbA1c.12 Another randomized, single-blinded trial conducted in India at a single center also indicated significant reductions in fasting blood glucose and HbA1c; however, the authors noted a delayed occurrence of this effect at six months.13 Fenugreek seeds also appear to be safe when consumed orally for up to six months at the typical doses.14
The small sample sizes and suboptimal quality of the studies reviewed limit any recommendations made on fenugreek used in patients with type 2 diabetes. Despite the few studies showing its efficacy in type 1 and type 2 diabetes, in the United States, fenugreek has been given generally recognized as safe (GRAS) status.15 However, pregnant women should not take fenugreek, since uterine contractions are associated with its use.16
Garlic
Garlic is an herb consumed in many dishes. However, many do not realize its potential effect on a person’s overall health. Garlic has been indicated as an alternative treatment for several disease states, including hypertension, hypercholesterolemia, coronary artery disease, vaginal candidiasis, atherosclerosis, and diabetes.17 Multiple mechanisms have been proposed to explain its effects, mostly attributing to the antimicrobial, antioxidant, and antihypertensive properties of the herb. Garlic’s glycemic effects seem to be caused by the increase in insulin secretion and sensitivity.18 The authors of a 2015 meta-analysis reviewed seven clinical studies of patients with diabetes who consumed garlic in varying formulations.19
The studies included patients who were taking garlic powder 600 mg to 1,500 mg daily, garlic oil 8.2 mg daily, or aged garlic extract 1,000 mg daily. The results showed it reduced fasting blood glucose by 1.7 mg/dL vs. control groups.19 Although the finding was statistically significant, a reduction of 1.7 mg/dL might not be considered clinically significant. The meta-analysis also did not include postprandial glucose or HbA1c outcomes because of only two studies reporting on these parameters. Older analyses also concluded garlic did not improve clinical outcomes in patients with diabetes.20,21 These results may have stemmed from the different preparations used, making it difficult to determine garlic’s effectiveness on glycemic levels in people with diabetes. Although glycemic effect has not been established using garlic, it has been suggested garlic exerts mild effects in hyperlipidemia and hypertension through extracts in divided doses 600 mg to 1,200 mg per day.
Gymnema sylvestre
G. sylvestre is a well-known plant native to India that has been used in Ayurvedic medicine for treating diabetes by dulling the taste buds to sweetness.22 Research suggests the leaf extract of G. sylvestre increases glucose absorption into the kidney, liver, and muscles as well as stimulates insulin release by increasing membrane permeability.23,24 The leaves of G. sylvestre also may produce anti-glycemic effects by causing an increase in the number of pancreatic islets and beta cells.25
In a controlled clinical trial, 27 patients with type 1 diabetes were treated with 200 mg G. sylvestre in addition to their insulin for six to 30 months.26 Study subjects reported a significant reduction in HbA1c from 12.8% to 9.5% after six to eight months of therapy vs. those treated only with insulin.26 Another study included 22 patients with type 2 diabetes treated with 400 mg G. sylvestre daily for 18 to 20 months in addition to a sulfonylurea, and HbA1c significantly decreased, from 11.9% to 8.5%.27
In both type 1 and type 2 diabetes, G. sylvestre has been studied for up to 2.5 years. There have been few randomized trials demonstrating the efficacy of G. sylvestre, but current studies suggest a long-term effect on hyperglycemia. Future studies are warranted to confirm the findings because of the small samples in the studies identified.
Among the herbal and dietary supplements presented in Part 2, the role that chromium, cinnamon, fenugreek, and garlic can play in glycemic management for patients with type 2 diabetes is rather unclear because of the mixed data from the various clinical trials. G. sylvestre, on the other hand, has been shown in clinical trials to demonstrate some long-term hyperglycemic management effects in both type 1 and type 2 diabetes. Since these trials were small, further investigation is needed to confirm the observed efficacy of G. sylvestre.
REFERENCES
- Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care 2004;27:2741-2751.
- Suksomboon N, Poolsup N, Yuwanakorn A. Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther 2014;39:292-306.
- Costello RB, Dwyer JT, Bailey RL. Chromium supplements for glycemic control in type 2 diabetes: Limited evidence of effectiveness. Nutr Rev 2016;74:455-468.
- Gunton JE, Cheung NW, Hitchman R, et al. Chromium supplementation does not improve glucose tolerance, insulin sensitivity, or lipid profile: A randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance. Diabetes Care 2005;28:712-713.
- Kleefstra N, Houweling ST, Jansman FG, et al. Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: A randomized, double-blind, placebo-controlled trial. Diabetes Care 2006;29:521-525.
- Jellin JM, Gregory PJ, Batz F, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 9th ed. Stockton, CA, Therapeutic Research Faculty, 2007.
- Franz MJ, Bantle JP, Beebe CA, et al. Nutrition principles and recommendations in diabetes. Diabetes Care 2004;27(suppl 1):S36-S46.
- Jarvill-Taylor KJ, Anderson RA, Graves DJ. A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3-L1 adipocytes. J Am Coll Nutr 2001;20:327-336.
- Khan A, Safdar M, Ali khan MM, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215-3218.
- Baker WL, Gutierrez-Williams G, White MC, et al. Effect of cinnamon on glucose control and lipid parameters. Diabetes Care 2008;31:41-43.
- Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type 2 diabetes: An updated systematic review and meta-analysis. Ann Fam Med 2013;11:452-459.
- Gong J, Fang K, Dong H, et al. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol 2016;194:260-268.
- Ranade M, Mudgalkar N. A simple dietary addition of fenugreek seed leads to the reduction in blood glucose levels: A parallel group, randomized single-blind trial. AYU 2017;38:24-27.
- Neelakantan N, Narayanan M, de Souza RJ, van Dam RM. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: A meta-analysis of clinical trials. Nutr J 2014;13:7.
- FDA. Food additive status list. Updated Oct. 24, 2019.
- DerMarderosian A, Beutler JA, eds. The Review of Natural Products. 8th ed. Lippincott Williams & Wilkins; 2014.
- Singh DK, Singh VK. Pharmacological effects of garlic (Allium sativum L.). Annual Review of Biomedical Sciences 2008;10.
- Liu CT, Hsu TW, Chen KM, et al. The antidiabetic effect of garlic oil is associated with ameliorated oxidative stress but not ameliorated level of pro-inflammatory cytokines in skeletal muscle of streptozotocin-induced diabetic rats. J Tradit Complement Med 2012;2:135-144.
- Hou LQ, Liu YH, Zhang YY. Garlic intake lowers fasting blood glucose: Meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr 2015;24:575-582.
- Ackermann RT, Mulrow CD, Ramirez G, et al. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001;161:813-824.
- Mulrow C, Lawrence V, Ackermann R, et al. Garlic: Effects on cardiovascular risks and disease, protective effects against cancer, and clinical adverse effects: Summary. In: AHRQ Evidence Report Summaries.
- Yoshikawa M, Murakami T, Kadoya M, et al. Medical foodstuffs. IX. The inhibitors of glucose absorption from the leaves of Gymnema sylvestre R. BR. (Asclepiadaceae): Structures of gymnemosides a and b. Chem Pharm Bull (Tokyo) 1997;45:1671-1676.
- Shanmugasundaram ER, Panneerselvam C, Samudram P, Shamugasundaram ERB. Enzyme changes and glucose utilization in diabetic rabbits: The effect of Gymnema sylvestre. J Ehtnopharmacol 1983;7:205-234.
- Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinology 1999;163:207-212.
- Shanmugasundaram ERB, Gopinath KL, Shanmugasundaram KR, Rajendran VM. Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. J Ethnopharmacol 1990;30:265-279.
- Shanmugasundaram ER, Rajeswari G, Baskaran K, et al. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol 1990;30:281-294.
- Baskaran K, Ahamath BK, Shanmugasundaram KR, et al. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 1990;30:295-305.
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