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 authors reviewed the current literature on the effectiveness and safety of commonly used herbal supplements in people with diabetes.
• A search was performed on the American Diabetes Association website to gather recommendations from the American Diabetes Care and Education Specialists about herbal products relating to diabetes management. Search results were cross-referenced with the Natural Medicines Database and Complementary & Alternative Medicine Supplement Use in People with Diabetes: A Clinician’s Guide for available studies regarding the identified herbal supplements’ safety and effectiveness.
• The available evidence for each supplement was inconclusive because of inconsistent results across studies, and very few studies reported adverse effects.
•There is insufficient evidence to make definitive recommendations on the role of herbal and dietary supplements used in people with diabetes. The current data warrant further research to produce high-quality results from randomized controlled trials. The inconsistent data on herbal and dietary supplements should be relayed to people with diabetes seeking alternative strategies as adjunctive options to manage diabetes.
Diabetes mellitus (DM), especially type 2 DM, is a major public health concern that affects about 34.1 million people in the United States.1 This chronic health condition, if not properly managed, can cause long-term complications as well as considerable morbidity and mortality in the affected population.2 In 2018, an estimated 1.5 million new cases of diabetes were diagnosed in U.S. adults aged 18 years or older, with more than half of these new cases in adults aged 45 to 64 years old.1
With an increasing number of diabetes cases, clinicians also are encountering more patients who are turning to complementary and alternative medicine (CAM) to help control their glucose levels. In a 2015 National Consumer Survey on the Medication Experience and Pharmacist Roles, 35% of 26,157 respondents in the study reported the use of at least one herbal medicine.3 In all, 3,050 respondents had diabetes, and 41.2% of the respondents reported the use of a dietary supplement.3 The data revealed that respondents with diabetes were associated with higher herbal medicine use when compared to respondents without chronic diseases (41% vs. 34%, P < 0.001).3 The results also showed that herbal medicine use increased as age increased among the respondents.3
Since CAM products are regulated as dietary supplements by the Food and Drug Administration, the effectiveness and safety of these products are regulated after they are available in the market, which means the quality and safety of these supplements can be highly variable.4 As more people with diabetes are reporting their use of CAM products in conjunction with prescription medications, it is important that clinicians understand what role these products play in diabetes management with the available evidence. By reviewing the current evidence behind these alternative therapies, medical practitioners will be better equipped to distill information for their patients and address the utility of these proposed diabetes supplements. This review will try to explore and present the current literature on commonly used herbal and dietary supplements among people with diabetes.
METHODS
An electronic literature search was performed on the American Diabetes Association website based on the recommendation from the American Association of Diabetes Educators (now named Association of Diabetes Care and Education Specialists) to discover what had been written about herbal products relating to diabetes management.5 These findings were cross-referenced with the Natural Medicines Database and Complementary & Alternative Medicine Supplement Use in People with Diabetes: A Clinician’s Guide regarding the identified products’ safety and effectiveness.6 Keywords included dietary supplements, herbal supplements, type 2 diabetes mellitus, Aloe vera, alpha lipoic acid, chromium, cinnamon, fenugreek, ginseng, ginger, gymnema, magnesium, nopal, and psyllium. The search was limited to studies published in the English language and searched from date of inception until 2019. We included systematic reviews, meta-
analysis, and randomized controlled trials. We excluded abstract-only articles, conference presentations, editorials, and studies with fewer than five participants. Articles were screened independently by the authors and included based on relevancy
RESULTS
The most popular supplements taken by patients are herbal supplements that come from natural sources, as opposed to other forms, such as vitamin or mineral mixtures.7 The authors have identified eleven herbal and dietary supplements — Aloe vera, alpha-lipoic acid, chromium, cinnamon, fenugreek, garlic, ginseng, magnesium, psyllium, gymnema, and nopal — that are commonly used among patients with diabetes.
However, because of limited quality control in dietary supplements, it is difficult to make firm recommendations without reviewing the current evidence on efficacy and proposed mechanisms in which these products work in patients with diabetes. This review article is divided into three parts, with parts 2 and 3 to be published in subsequent issues of Integrative Medicine Alert. Aloe vera and alpha-lipoic acid are included in this part.
ALOE VERA
There are more than 300 species in the Aloe genus, and one is extremely well-known worldwide. Aloe barbadensis, otherwise known as Aloe vera, is a renowned plant of the Liliaceae family, known for its many medicinal properties.8 The spiky succulent plant contains gel and juice, which has become a commercial supplement and cosmetic. It is believed that Aloe vera possesses antioxidant, anticancer, anti-inflammatory, laxative, and anti-atherosclerotic properties.9
There are multiple existing hypotheses on why Aloe vera can have potential benefits in diabetes management. One hypothesis states that Aloe vera lowers blood glucose levels through its anti-inflammatory effects. Type 2 DM is an inflammatory disease associated with oxidative stress of the pancreas, which leads to beta-cell dysfunction and insulin resistance.10 Clinical research shows that Aloe vera can reduce fasting blood glucose levels by 30 mg/dL to 46.6 mg/dL and hemoglobin A1c (HbA1c) by 0.41% to 1.05% in adults with prediabetes and diabetes.11-13 Another hypothesis proposes that a constituent of the Aloe vera plant, glucomannan, is the agent that possesses the hypoglycemic effects.14 Glucomannan is a hydrosoluble agent believed to promote satiety and delaying intestinal absorption becuase of its increased viscosity.15 There has been a variety of doses and dosage forms, ranging from 100 mg to 1,000 mg of its powder to 15 mL to
150 mL of its juice formulation, suggested to be efficacious in lowering blood glucose.11-13 However, because of the heterogeneity of the available studies, the mixed evidence on Aloe vera’s effectiveness hinders the validity of the reported findings.
ALPHA-LIPOIC ACID
Alpha-lipoic acid (ALA) is an antioxidant that has been hypothesized to improve carbohydrate disturbances.15,16 ALA is a naturally occurring antioxidant that promotes the transport of glucose into cells of muscles.16 Additionally, its use has been suggested to have beneficial effects in peripheral neuropathy in patients with type 2 diabetes.17 The suggested effective dose to improve insulin sensitivity and fasting blood glucose is 600 mg to 1,800 mg/day orally for four to eight weeks.16 However, conflicting evidence does exist, which suggests no effect on insulin sensitivity.12 Dosages of 600 mg to 1,800 mg daily have been shown to be beneficial for patients experiencing pain, numbness, and prickling of extremities associated with neuropathy.18
Table 1 summarizes the common dosages and adverse effects of the two supplements included in this part of the review. Table 2 includes meta-analyses, systematic reviews, and major clinical trials pertinent to the two supplements. For more information on the specific studies analyzed in Table 2, visit https://bit.ly/3eRfp3g.
Table 1. Common Dosages and Adverse Effects of Herbal and Dietary Supplements* |
|||
|
Supplement |
Typical Dosages |
Adverse Effects |
Drug Interactions |
|
Aloe vera |
|
|
|
|
Alpha-lipoic acid |
|
|
|
|
IV: intravenous *Information in this table was acquired from the Natural Medicines Database |
|||
Table 2. Common Dosages and Adverse Effects of Herbal and Dietary Supplements* |
|||||
|
Supplement |
Notable Studies |
Type of Study |
Participants |
Measurements |
Findings |
|
Aloe vera |
Zhang et al 20169 |
Meta-analysis of five RCTs |
415 participants with prediabetes and untreated diabetes |
HbA1c and FBG |
|
|
Dick et al 201610 |
Meta-analysis of nine RCTs |
283 |
HbA1c and FBG |
|
|
|
Suksomboon et al 201611 |
Meta-analysis of eight RCTs |
470 participants with pre-diabetes and type 2 diabetes |
HbA1c and FBG |
|
|
|
Alpha-lipoic acid |
Ziegler et al 199515 (ALADIN study) |
RCT with three doses (1,200 mg, 600 mg, and 100 mg ALA) and placebo |
260 non-insulin-dependent patients with diabetes and symptomatic peripheral neuropathy |
Neuropathic symptoms; Hamburg Pain Adjective List; Neuropathy Symptom and Disability Scores |
|
|
Reljanovic et al. 199921 (ALADIN II Study) |
RCT |
65 patients with type 1 or 2 diabetes and who experienced symptomatic polyneuropathy |
Neuropathy Disability Scores; nerve measurements |
|
|
|
Ziegler et al 199922 (ALADIN III Study) |
RCT |
509 patients with type 2 diabetes and symptomatic polyneuropathy |
Total Symptom Score for neuropathic symptoms in the feet; Neuropathy Impairment Score |
|
|
|
RCT: randomized controlled trial; FBG: fasting blood glucose; WMD: weighted mean difference; CI: confidence interval; FPG: fasting plasma glucose; MD: mean difference |
|||||
DISCUSSIONS
Compared to patients without diabetes, patients with diabetes are 1.6 times more likely to include CAM as a component of their diabetes management plans, thus more prone to negative consequences — e.g., side effects and drug interactions — resulting from herbal and dietary supplement usage.19 These products often are purchased over the counter or through mail order, so the consumers/patients with DM might be confused about the product contents and labels, adding to the list of safety concerns. For that reason, patients might be at risk of purchasing products that do not match their stated claims if the products have not gone through a third-party verification/testing process.
To ensure safety from the standpoint of clinicians, it is crucial to ask patients at every visit whether any herbal or dietary supplements were added since the last medical appointment to identify potential drug-supplement interactions, side effects, or additive effects when used with antidiabetic medications if new agents were added. Although Aloe vera has been used for skin treatment and incorporated into drugs as laxatives, there is no long-term evidence yet to suggest its effectiveness in diabetes management. ALA — functioning similarly to B-complex vitamin — has been used in peripheral neuropathy treatment, even secondary to diabetes.20,21 In Part 2 of this review article, discussions will focus on chromium, cinnamon, fenugreek, garlic, and ginseng, summarizing common dosages and adverse effects, as well as pertinent studies.
ACKNOWLEDGMENT
Thanks to Ivy Yu, PharmD, and Chau Huynh, PharmD, for their contributions on gathering information for this review article.
REFERENCES
- Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020. Atlanta;2020.
- Centers for Disease Control and Prevention. About Diabetes. Atlanta;2017.
- Rashrash M, Schommer JC, Brown LM. Prevalence and predictors of herbal medicine use among adults in the United States. J Patient Exp 2017; 4:108-113.
- Bailey RL. Current regulatory guidelines and resources to support research of dietary supplements in the United States. Crit Rev Food Sci Nutr 2020;60:298-309.
- Cefalu WT, Stephens JM, Ribnicky DM. Diabetes and herbal (botanical) medicine. In: Benzie IFF, Wachtel-Galor S, eds. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition.CRC Press/Taylor & Francis;2011: https://www.ncbi.nlm.nih.gov/books/NBK92755/
- National Center for Complementary and Integrative Health. Aloe Vera. Updated August 2020. https://nccih.nih.gov/health/aloevera
- Alinejad-mofrad S, Foadoddini M, Saadatjoo SA, Shayesteh M. Improvement of glucose and lipid profile status with Aloe vera in pre-diabetic subjects: A randomized controlled-trial. J Diabetes Metab Disord 2015;14:22.
- Kaneto H, Katakami N, Kawamori D, et al. Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 2007;9:355-366.
- Zhang Y, Liu W, Liu D, et al. Efficacy of Aloe vera supplementation on prediabetes and early non-treated diabetic patients: A systematic review and meta-analysis of randomized controlled trials. Nutrients 2016; 8:388.
- Dick WR, Fletcher EA, Shah SA. Reduction of fasting blood glucose and hemoglobin A1c using oral Aloe vera: A meta-analysis. J Altern Complement Med 2016;22:450-457.
- Suksomboon N, Poolsup N, Punthanitisarn S. Effect of Aloe vera on glycaemic control in prediabetes and type 2 diabetes: A systematic review and meta-analysis. J Clin Pharm Ther 2016;41:180-188.
- Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care 2003;26:1277-1294.
- Keithley JK, Swanson B, Mikolaitis SL, et al. Safety and efficacy of glucomannan for weight loss in overweight and moderately obese adults. J Obes 2013;2013:610908.
- Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: A placebo-controlled pilot trial. Free Radic Biol Med 1999;27:309-314.
- Golbidi S, Badran M, Laher I. Diabetes and alpha lipoic acid. Front Pharmacol 2011;2:69.
- de Oliveira AM, Rondó PH, Luzia LA, et al. The effects of lipoic acid and alpha-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial. Diabetes Res Clin Pract 2011;92:253-260.
- Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995;38:1425-1433.
- Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care 2004;27:2741-2751.
- 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.
- Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): A two-year multicenter randomized double-blind placebo controlled trial (ALADIN II): Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Biol Med 1999;31:171-179.
- Reljanovic M, Reichel G, Rett K, Lobisch M, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): A two-year multicenter randomized double-blind placebo controlled trial (ALADIN II): Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res 1999;31:171-179.
- Ziegler D, Hanefeld M, Ruhuan KJ, et al. Treatment of symptomatic diabtic polyneuropathy with the antioxidant alpha-lipoic acid: A 7-month multicenter randomized controlled trial (ALADIN III Study). Diabetes Care 1999;22:1296-301.
With an increasing number of diabetes cases, clinicians also are encountering more patients who are turning to complementary and alternative medicine to help control their glucose levels. In a 2015 National Consumer Survey on the Medication Experience and Pharmacist Roles, 35% of 26,157 respondents in the study reported the use of at least one herbal medicine. In all, 3,050 respondents had diabetes, and 41.2% of the respondents reported the use of a dietary supplement.3 The data revealed that respondents with diabetes were associated with higher herbal medicine use when compared to respondents without chronic diseases (41% vs. 34%, P < 0.001). The results also showed that herbal medicine use increased as age increased among the respondents.
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