The Safety and Efficacy of Common Herbal and Dietary Supplements in Patients with Type 2 Diabetes Mellitus: Part 2
August 1, 2021
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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, CA.
Dr. Wai is a graduate of Touro University California College of Osteopathic Medicine, Residency Training at Riverside Community Health/University of California Riverside, Riverside, CA.
SUMMARY POINTS
- The effects of chromium, cinnamon, fenugreek, and garlic in type 2 diabetes management are unclear in the evidence collected from various meta-analyses.
- Gymnema sylvestre has been shown to reduce glycemic levels significantly in two small long-term studies. However, more studies are needed to confirm its effectiveness.
In Part 1 of this literature review, Aloe vera and alpha-lipoic acid were discussed 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. See Table 1 for common dosages and adverse effects of the supplements in this review. Table 2 summarizes some notable studies.
Table 1. Common Dosages and Adverse Effects of Herbs and Dietary Supplements* | |||
|
Supplement |
Typical Dosages |
Adverse Effects |
Drug Interactions |
|
Chromium |
|
Headaches, insomnia, sleep disturbances, irritability, mood changes, kidney damage, weight gain, gastrointestinal effects |
|
|
Cinnamon |
|
Hepatotoxicity |
|
|
Fenugreek |
|
Diarrhea, dyspepsia, abdominal distention, nausea, and flatulence |
|
|
Garlic |
|
Breath odor, mouth and gastrointestinal burning or irritation, heartburn, flatulence, allergic reactions, and (rarely) topical lesions and burns |
|
|
Gymnema sylvestre |
|
Hepatitis |
|
|
NSAIDs: non-steroidal anti-inflammatory drugs Source: Jellin JM, Gregory P, Batz F, et al. Natural Medicines Comprehensive Database. 3rd ed. Pharmacists Letter; 2000. | |||
Table 2. Summary of Notable Studies for Dietary and Herbal Supplements | |||||
|
Supplement |
Notable Studies |
Type of Study |
Participants |
Measurements |
Findings |
|
Chromium |
Costello et al 20163 |
Review of 20 RCTs |
N/A |
HbA1c and FBG |
|
|
Per the authors of this review with RCTs, they did not find adequate reasons for recommending chromium dietary supplements for glycemic management. The authors also did not find major safety issues being presented in these clinical trials, recommending future meta-analyses to only include high-quality studies with similar formulations of chromium and comparable study criteria. | |||||
|
Suksomboon et al 20142 |
Meta-analysis of 25 RCTs |
N/A |
HbA1c and FPG |
| |
|
Overall recommendations/assessments from the authors: Chromium mono-supplementation above the daily dose of 200 μg was shown to improve glycemic management; in addition, the monotherapy was also shown to reduce triglycerides and to increase HDL-C levels significance. Thus, chromium supplementation based on the reviewed evidence exerted a positive effect on glycemic management in patients with diabetes. | |||||
|
Cinnamon |
Baker et al 200810 |
Meta-analysis of five RCTs |
n = 282 (type 1 and 2 diabetes) |
HbA1c and FBG |
|
|
Overall recommendations/assessments from the authors: The median duration combining treatment and follow-up time periods in these trials was 12 weeks. This duration would have been sufficient to reveal clinically significant changes in FBG, but it was too short for seeing a full effect of treatment on HbA1c. Although cinnamon does not appear to enhance glycemic management in participants with diabetes, its ability to prevent type 2 diabetes in those with pre-diabetes is unknown. | |||||
|
Allen et al 201311 |
Meta-analysis of 10 RCTs |
n = 543 |
HbA1c and FPG |
| |
|
See Table 2A at https://bit.ly/3gU1ZDJ for more findings. | |||||
|
RCT: randomized controlled trial; HbA1c: hemoglobin A1c; FBG: fasting blood glucose; FPG: fasting plasma glucose; CI: confidence interval; HDL-C: high-density lipoprotein cholesterol | |||||
Table 2. Summary of Notable Studies for Dietary and Herbal Supplements, continued | |||||
|
Supplement |
Notable Studies |
Type of Study |
Participants |
Measurements |
Findings |
|
Fenugreek |
Gong et al 201612 |
Meta-analysis of 12 RCTs |
n = 1,173 (type 2 diabetes and prediabetes) |
HbA1c, FBG, and 2-h PBG (post-prandial blood glucose) |
|
|
See Table 2B at https://bit.ly/3gU1ZDJ for more findings. | |||||
|
Garlic |
Hou et al 201519 |
Meta-analysis of seven RCTs |
n = 513 (type 2 diabetes and healthy patients |
FBG |
|
|
See Table 2C at https://bit.ly/3gU1ZDJ for more findings. | |||||
|
Gymnema sylvestre |
Baskaran et al 199027 |
RCT |
n = 22 (type 2 diabetes) |
BG, HbA1c |
|
|
RCT: randomized controlled trial; HbA1c: hemoglobin A1c; FBG: fasting blood glucose CI: confidence interval | |||||
CHROMIUM RESULTS
Trivalent chromium, or chromium-3, is a trace element that is 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 that 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 concluded that chromium supplementation had a significant and positive lowering effect on fasting plasma glucose levels and an overall decline of ≥ 0.5% in hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes.3 However, the reported trials had 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 of the randomized, clinical trials addressed adverse events with chromium supplementation, which included skin rash, constipation, and other gastrointestinal symptoms.4,5
CHROMIUM DISCUSSION
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 the management of type 2 diabetes. The American Diabetes Association expressed no conclusive evidence supporting the use of chromium supplementation in diabetes.7
CINNAMON RESULTS
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 This meta-analysis concluded that 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% confidence interval, -40.52 to -8.67 mg/dL) but no statistically significant reduction in HbA1c.11
CINNAMON DISCUSSION
Cinnamon’s role in patients with diabetes is currently unknown. The conflicting available evidence includes a small number of studies with high heterogeneity where double-blinded procedures may not have been sufficient. In addition, the amount of cinnamon used in studies varied widely, and some studies used amounts equivalent to about a half-teaspoon.
FENUGREEK RESULTS
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 utilization.12 Pooled results of a meta-analysis shows that 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 reported significant reductions in fasting blood glucose and HbA1c; however, the study also 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, as noted in Table 1.14
FENUGREEK DISCUSSION
The small sample sizes and suboptimal quality of the studies reviewed limit any recommendations being made on fenugreek used in patients with type 2 diabetes. Despite having a limited number of 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 use fenugreek, since uterine contractions are associated with its use.16
GARLIC RESULTS
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 a variety of 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 as a result of the increase in insulin secretion and sensitivity.18 A 2015 meta-analysis reviewed seven clinical studies that looked at patients with diabetes who consumed garlic in varying formulations.19
The studies looked at patients taking garlic powder 600 mg to 1,500 mg daily, garlic oil 8.2 mg daily, or aged garlic extract 1,000 mg daily, and the results showed that it reduced fasting blood glucose by 1.7 mg/dL compared to the 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 that garlic did not improve clinical outcomes in people with diabetes.20,21
GARLIC DISCUSSION
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 that garlic exerts mild effects in hyperlipidemia and hypertension through extracts in divided doses 600 mg to 1,200 mg per day.
GYMNEMA SYLVESTRE RESULTS
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 may also have 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 compared to those treated only with insulin.26 Another study included 22 patients with type 2 diabetes who were 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
GYMNEMA SYLVESTRE DISCUSSION
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.
CONCLUSION
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. In Part 3 of this literature review, ginseng, magnesium, nopal, and psyllium will be discussed in detail along with some final thoughts on all the herbal and dietary supplements presented in this series of articles.
ACKNOWLEDGMENT
Thanks to Ivy Yu, PharmD, and Chau Huynh, PharmD, for their contributions on gathering information for this review article.
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.
- United States Food and Drug Administration. Food additive status list. Updated Oct. 24, 2019. https://www.fda.gov/food/food-additives-petitions/food-additive-status-list#ftnF
- 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. doi: http//dx.doi.org/10.5016/1806-8774.2008.v10p6
- 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. https://www.ncbi.nlm.nih.gov/books/NBK11910/
- 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.
In Part 1 of this literature review, Aloe vera and alpha-lipoic acid were discussed 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.
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