The Safety and Efficacy of Common Herbal and Dietary Supplements in Patients with Type 2 Diabetes Mellitus: Part 3
September 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 evidence on ginseng, magnesium, nopal, and psyllium relating to type 2 diabetes management is inconsistent, thus more studies are warranted to shed some light on their effectiveness regarding glycemic management.
- Although most of the studies included in this literature review series were randomized clinical trials and meta-analyses of randomized clinical trials, there was high heterogeneity across the studies and data were considered to have limited quality because of various preparations of supplements, dosages of supplements, and duration of treatment, as well as different subject cohorts.
One of the reasons to discuss complementary and alternative medicine (CAM) supplements used by patients with diabetes is that this subpopulation is 1.6 times more likely than those without diabetes to consume CAM supplements. Thus, patients with diabetes might be more prone to problems relating to CAM.1
While part 1 of this literature review series discussed Aloe vera and alpha-lipoic acid, part 2 of this series presented information on chromium, cinnamon, fenugreek, garlic, and Gymnema sylvestre. This last part provides study findings relating to ginseng, magnesium, nopal, and psyllium. Table 1 summarizes the common dosages, adverse effects, and drug interactions of the herbal supplements discussed in this review, and Table 2 summarizes the studies and their findings examined in this review.
Table 1. Common Dosages and Adverse Effects of Herbs and Dietary Supplements | |||
Supplement |
Typical Dosages |
Adverse Effects |
Drug Interactions |
Ginseng |
|
Insomnia, restlessness, increased blood pressure or heart rate, headache, mastalgia, mood changes, nervousness |
|
Magnesium |
|
Gastrointestinal irritation, nausea, vomiting, diarrhea, hypermagnesemia when given to renally impaired patient |
|
Nopal |
|
Diarrhea, nausea, abdominal fullness, headache |
|
Psyllium |
|
Flatulence, bloating |
|
Source: Jellin JM, Gregory P, Batz F, et al. Natural Medicines Comprehensive Database. 3rd ed. Therapeutic Research Faculty; 2000. | |||
Table 2. Summary of Notable Studies for Dietary and Herbal Supplements | |||||
Supplement |
Notable Studies |
Type of Study |
Participants |
Measurements |
Findings |
Ginseng |
Kim et al (2011)3 |
Meta-analysis of four RCTs |
n = 76 (type 2 diabetes) |
Fasting glucose and HbA1c |
|
See Table 2A at https://bit.ly/3smpU3N. | |||||
Magnesium |
Song et al (2006)13 |
Meta-analysis of nine RCTs |
n = 370 (type 2 diabetes) |
Fasting glucose and HbA1c |
|
See Table 2B at https://bit.ly/3smpU3N. | |||||
Nopal |
Gouws et al (2019)18 |
Systematic review of 12 RCTs with cladode leaf and four RCTs with a mix of cladode leaf/ fruit |
Healthy people and patients with type 2 diabetes |
Blood glucose levels |
|
See Table 2C at https://bit.ly/3smpU3N. | |||||
Psyllium |
Gibb et al (2015)24 |
Meta-analysis of 35 RCTs with 10 studies on participants with type 2 diabetes |
1,267 healthy and at-risk subjects) and 245 participants with type 2 diabetes |
HbA1c, fasting glucose, and postprandial glucose |
|
See Table 2D at https://bit.ly/3smpU3N. | |||||
RCT: randomized controlled trial; HbA1c: hemoglobin A1c; FPG: fasting plasma glucose; CI: confidence interval; FBG: fasting blood glucose | |||||
GINSENG RESULTS
American ginseng has shown to be superior to Chinese ginseng in reduction of blood glucose levels in numerous study findings.2-4 One study with 10 nondiabetic participants indicated that administration resulted in a change of 19% ± 22% and 22% ± 17% for subjects with type 2 diabetes mellitus.5 A second study with 10 participants with type 2 diabetes produced similar results when comparing administration with placebo, 3 g, 6 g, or 9 g of ginseng. Administration resulted in a significantly (P < 0.05) incremental glycemic reduction at 30 minutes (16.3%, 18.4%, and 18.4%, respectively), 45 minutes (12.5%, 14.3%, and 14.3%, respectively), and 120 minutes (59.1%, 40.9%, and 45.5%, respectively).6 Taking American ginseng 100 mg to 200 mg daily for eight weeks also reduced fasting blood glucose levels in patients with type 2 diabetes.7
Although the number of experimental trials and participants was small, these studies suggest American ginseng is superior to Chinese ginseng for glycemic management.
GINSENG DISCUSSION
Ginseng is one of the 700 plant species, including carrots, parsnips, and celery, belonging to the Araliaceae family. This herb has existed for thousands of years, first being discovered in Manchuria, China. Today, ginseng continues to be a relevant topic of holistic alternatives in the treatment of cancer, diabetes, and cardiovascular disease.
MAGNESIUM RESULTS
Magnesium is an electrolyte that plays many physiological roles in the human body, ranging from supporting a healthy immune system to maintaining normal nerve and muscle function. This electrolyte also aids in regulating blood glucose levels and serves as a cofactor in the production of energy and protein.8
Two studies indicated that magnesium supplementation may reduce the risk of developing type 2 diabetes, resulting in higher fasting insulin levels in people without diabetes.9,10 Three individual studies and one meta-analysis indicated that supplementation of various forms and dosages of magnesium in patients with type 2 diabetes resulted in a reduction of fructosamine, fasting blood glucose, two-hour postprandial blood glucose, and hemoglobin A1c (HbA1c) levels at the end of each trial.11-14 In contrast, two individual randomized controlled trials yielded no significant difference between treatment and placebo groups at the end of the studies.15,16
MAGNESIUM DISCUSSION
Hypomagnesemia is a condition that occurs in 25% to 38% of patients who have type 2 diabetes, and it is especially common in patients with poorly managed diabetes.17 Lower serum magnesium levels also are associated with a rapid decline in renal function.9 The information available for magnesium as a supplement in managing type 2 diabetes has had mixed results, mostly owing to the different variations of dosing and formulations. When magnesium is given orally, it generally is well-tolerated, but it may cause symptoms, such as nausea, vomiting, and diarrhea. Due to variations in dosing and formulations, it is difficult to assess magnesium’s efficacy on reducing blood glucose in patients with a history of diabetes.
NOPAL RESULTS
Nopal, also known as prickly pear, is commonly used for food in Mexico and the southwestern United States. The specific species Opuntia streptacantha has been researched for its potential for glycemic management. A meta-analysis in 2019 of the Opuntia spp. concluded that, specifically, the cladode, or leaf, of the cactus had significant antihyperglycemic effects in healthy people and patients with type 2 diabetes.18
However, a majority of the studies for cladode consumption were performed by the Frati et al group, and glucose levels were measured after a single consumption of Opuntia spp. cladode.18 The most recent studies by Linares et al, Bacardia-Gascon et al, and Guevare-Cruz et al spanned a period of three to six weeks, but two out of the three studies reported no significant difference to placebo after glucose tolerance testing.19-21 The variation in duration and conflicting results from each trial have created doubt on nopal’s long-term effects on blood glucose management.
NOPAL DISCUSSION
O. streptacantha contains high-soluble fiber that may contribute to its antiglycemic effect by slowing down carbohydrate absorption.22 Nopal also may have synergistic effects with insulin, but an experiment with pancreatectomized animals suggests its antiglycemic effects do not completely depend on the presence of insulin.23
Psyllium Results
A meta-analysis consisting of 35 randomized controlled trials reported significant improvement in both fasting blood glucose concentration and HbA1c, indicating that psyllium dosed before meals would be an effective addition to a lifestyle intervention program.24
In patients who were being treated for type 2 diabetes, long-term psyllium use showed a significant mean reduction in fasting blood glucose by -37 mg/dL (P < 0.001) and mean HbA1c reduction of -0.97% (P = 0.048).24 A more recent randomized controlled study published in 2016 reported significant reduction in body mass index when compared to the control group in patients with type 2 diabetes (31.8 kg/m2 to 30.9 kg/m2 vs. 31.5 kg/m2 to 31.8 kg/m2; P < 0.001).25 It also reported improvements in fasting blood glucose levels (163 mg/dL to 119 mg/dL) and HbA1c levels (8.5% to 7.5%).25
PSYLLIUM DISCUSSION
Psyllium is commonly known as a dietary fiber used as a bulk-forming laxative to treat chronic constipation and for softening stools in a wide range of conditions. Psyllium is classified as a soluble fiber that can dissolve in water and form a gel-like material. The forming of a viscous material reduces digestion and absorption of carbohydrates, thus delaying glucose absorption into the circulation.24 Although the current data show that psyllium would be an effective intervention in patients with diabetes, the variability of subject cohorts, protocols, and quality of trials may obscure information. Additional studies are needed to determine the best way to incorporate psyllium into clinical practice.
OVERALL ANALYSES
The efficacy of each supplement on lowering blood glucose levels varied greatly across the available evidence. The more promising supplements that seem to have a favorable outcome in patients with diabetes are A. vera, psyllium, G. sylvestre, and fenugreek. In particular, the available data suggest that these four supplements may reduce HbA1c levels in patients with diabetes, and, thus, may have long-term effects. In addition to these four supplements, studies suggest that magnesium, cinnamon, and garlic also may have an effect on fasting blood glucose levels.
However, magnesium, cinnamon, nopal, and garlic do not seem to have any long-term glycemic effects (e.g., HbA1c). Ginseng did not have strong supportive evidence for glycemic control because of the low number of studies and participants, but findings suggest that American ginseng may have postprandial glucose reduction. Most, if not all, of the studies varied greatly in terms of their study methods, dosages, and types of preparations of the supplements. These factors were accounted for when analyzing the data, making it difficult to make any definitive conclusions on the effectiveness of these supplements.
Magnesium, garlic, cinnamon, chromium, and alpha-lipoic acid all had conflicting research findings. Some studies reported reductions in glycemic levels while others reported no effect at all. This observation may suggest that there has not been a consistent benefit when taking these supplements and may vary in its effectiveness from individual to individual.
Because of inconsistent data from these supplements to support their effectiveness in glucose management, no conclusions could be made at this point. Interestingly, alpha-lipoic acid seems to have beneficial effects on peripheral neuropathy in patients with diabetes, which was not reported for any of the other supplements.
This suggests that further research is warranted for alpha-lipoic acid on its potential effect in patients with diabetes and diabetic peripheral neuropathy. Chromium was the most widely investigated supplement, and different studies have reported that there is no beneficial effect for its supplementation. However, data suggest that chromium’s metabolic effects may not be significant until there is a significant chromium deficiency.26
The available evidence reviewed for each supplement appears to have high heterogeneity across the studies. These studies that we have included primarily were randomized clinical trials and meta-analyses of randomized clinical trials. However, most reported data were deemed to have limited quality because of the different preparations of supplements, dosages of supplements, duration of treatment, and different subject cohorts. This has made the interpretation of currently available data especially difficult, thus hindering any firm recommendations to be made on any of these supplements. Additionally, the effective doses of these supplements were unable to be identified because of the various formulations and dosages used in the studies, leading to a wide range of therapeutic responses or lack thereof.
Few studies reported on the safety of these products. The most common side effect among these supplements was gastrointestinal-related, which included nausea, vomiting, gastrointestinal irritation, and diarrhea. One specific safety study on American ginseng showed no renal, hepatic, or hematologic side effects.27 Some subjects also experienced contact dermatitis with garlic.28,29 The lack of adverse effect reports may be because of publication bias to record positive effects or simply that there were no notable side effect differences between the placebo group and the treatment groups.
Nonetheless, if patients were taking herbal supplements in addition to prescription medications, it would be important to evaluate possible safety concerns. Further studies are warranted to better understand the safety of these herbal and dietary supplements, which includes toxicity levels and drug interactions. Determining their safety is especially important because the manufacturers are not required to complete any safety analyses before these products reach the market.
ACKNOWLEDGMENT
Thanks to Ivy Yu, PharmD, and Chau Huynh, PharmD, for their contributions on gathering information for this review article.
REFERENCES
- Egede LE, Ye X, Zeng D, Silverstein MD. The prevalence and pattern of complementary and alternative medicine use in individuals with diabetes. Diabetes Care 2002;25:324-329.
- Ni HX, Yu NJ, Yang XH. The study of ginsenoside on PPAR-gamma expression of mononuclear macrophage in type 2 diabetes. Mol Biol Rep 2010;37:2975-2979.
- Kim S, Shin BC, Lee MS, et al. Red ginseng for type 2 diabetes mellitus: A systematic review of randomized controlled trials. Chin J Integr Med 2011;17:937-944.
- Reeds DN, Patterson BW, Okunade A, et al. Ginseng and ginsenoside Re do not improve beta-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes. Diabetes Care 2011;34:1071-1076.
- Vuksan V, Sievenpiper JL, Koo VY, et al. American ginseng (Panax quinquefolius L.) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med 2000;160:1009-1013.
- Vuksan V, Stavro MP, Sievenpiper JL, et al. Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes. Diabetes Care 2000;23:1221-1226.
- Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care 1995;18:1373-1375.
- National Institutes of Health. Magnesium: Fact sheet for health professionals. Updated Aug. 11, 2021. ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/#h5
- Fung TT, Manson JE, Solomon CG, et al. The association between magnesium intake and fasting insulin concentration in healthy middle-aged women. J Am Coll Nutr 2003;22:533-538.
- Lopez-ridaura R, Willett WC, Rimm EB, et al. Magnesium intake and risk of type 2 diabetes in men and women. Diabetes Care 2004;27:134-140.
- de Lordes Lima M, Cruz T, Pousada JC, et al. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care 1998;21:682-686.
- Rodríguez-Morán M, Guerrero-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: A randomized double-blind controlled trial. Diabetes Care 2003;26:1147-1152.
- Song Y, He K, Levitan EB, et al. Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: A meta-analysis of randomized double-blind controlled trials. Diabet Med 2006;23:1050-1056.
- Solati M, Ouspid E, Hosseini S, et al. Oral magnesium supplementation in type II diabetic patients. Med J Islam Repub Iran 2014;28:67.
- Paolisso G, Scheen A, Cozzolino D, et al. Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients. J Clin Endocrinol Metab 1994;78:1510-1514.
- Eibl NL, Kopp HP, Nowak HR, et al. Hypomagnesemia in type II diabetes: Effect of a 3-month replacement therapy. Diabetes Care 1995;18:188-192.
- Pham PCT, Pham PMT, Pham PAT, et al. Lower serum magnesium levels are associated with more rapid decline of renal function in patients with diabetes mellitus type 2. Clin Nephrol 2005;63:429-436.
- Gouws CA, Georgousopoulou EN, Mellor DD, et al. Effects of the consumption of prickly pear cacti (Opuntia spp.) and its products on blood glucose levels and insulin: A systematic review. Medicina (Kaunas) 2019;55:138.
- Linarés E, Thimonier C, Degre M. The effect of NeOpuntia on blood lipid parameters — risk factors for the metabolic syndrome (syndrome X). Adv Ther 2007; 24:1115-1125.
- Bacardi-Gascon M, Dueñas-Mena D, Jimenez-Cruz A. Lowering effect on postprandial glycemic response of nopales added to Mexican breakfasts. Diabetes Care 2007;30:1264-1265.
- Guevara-Cruz M, Tovar AR, Aguilar-Salinas CA, et al. A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome. J Nutr 2012;142:64-69.
- Shapiro K, Gong WC. Natural products used for diabetes. J Am Pharm Assoc (Wash) 2002;42:217-226.
- Ibañez-Camacho R, Román-Ramos R. Hypoglycemic effect of Opuntia cactus. Arch Invest Med (Mex) 1979;10:223-230.
- Gibb RD, Mcrorie JW Jr., Russell DA, et al. Psyllium fiber improves glycemic control proportional to loss of glycemic control: A meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus. Am J Clin Nutr 2015;102:1604-1614.
- Abutair AS, Naser IA, Hamed AT. Soluble fibers from psyllium improve glycemic response and body weight among diabetes type 2 patients (randomized controlled trial). Nutr J 2016;15:86.
- 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.
- Mucalo I, Jovanovski E, Vuksan V, et al. American ginseng extract (Panax quinquefolius L.) is safe in long-term use in type 2 diabetic patients. Evid Based Complement Alternat Med 2014;2014:969168.
- American Association of Diabetes Educators. The role of dietary supplements in glycemic and cholesterol management. Published 2019. https://www.diabeteseducator.org/docs/default-source/living-with-diabetes/tip-sheets/aade-dietary-supplements-ts-2-final.pdf?sfvrsn=13
- Shane-McWhorter L. Complementary and Alternative medicine (CAM) Supplement Use in People With Diabetes: A Clinician’s Guide. American Diabetes Association; 2007.
While part 1 of this literature review series discussed Aloe vera and alpha-lipoic acid, part 2 of this series presented information on chromium, cinnamon, fenugreek, garlic, and Gymnema sylvestre. This last part provides study findings relating to ginseng, magnesium, nopal, and psyllium.
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