US Pharm. 2018;43(10):35-41.
ABSTRACT: Dietary supplements are commonly used in the United States, with reports of their use among patients with diabetes ranging from 22% to 67%. Patients with diabetes are even more likely to use dietary supplements than the general population, with a subset of patients preferring “natural” therapies to evidence-based prescriptions. Pharmacists should ensure that patients are aware of the lack of FDA oversight over dietary supplements and the potential for serious adverse events.
Diabetes is the seventh leading cause of death in the United States, and patients often have a fear of complications.1,2 More than 30 million individuals in the U.S. are afflicted with diabetes, and 84 million more have prediabetes.1 Patients with diabetes are more likely to use dietary supplements than people without diabetes. 3 Over half of patients at an outpatient diabetes-care clinic reported daily use of dietary supplements, with use being twice as common in type 2 diabetes as in type 1 diabetes.4 A1C was found to be lower in patients who reported some type of supplement use, although which supplements were used was not reported. Other reports have found dietary-supplement use to range from 22% to 67% in patients with diabetes.5
Dietary supplements are defined as a product taken by mouth that contains a dietary ingredient intended to supplement the diet. These can contain vitamins, herbs, minerals, amino acids, and other substances, such as enzymes, metabolites, and organ tissues.6 Dietary supplements are commonly available as tablets, softgels, capsules, liquids, powders, and bars.6 It is important for pharmacists to remember that since dietary supplements are categorized as foods, they are not subject to the same regulatory standards and oversight by the FDA as prescription medications.7 Manufacturers are only required to provide the FDA evidence of safety and efficacy before marketing the product if it is a new dietary ingredient, and the FDA cannot remove the product from the market until it is proven unsafe.6
Pharmacists, therefore, should ensure that patients are aware of the lack of oversight and how to report adverse effects potentially associated with dietary-supplement use. More than 6,300 serious adverse events involving dietary supplements were reported to the FDA between 2007 and 2012, including emergency-room visits, hospitalizations, and 115 deaths.8
Many explanations exist for patient interest in using dietary supplements to manage diabetes. These can include a desire to avoid the adverse effects of traditional medications, expensive medication cost, belief that supplements are “natural” and without risks, powerful messages from family and friends, and diabetes severity and duration.5
Dietary Supplements for Diabetes Management
Numerous dietary supplements have been used to treat diabetes and associated complications (TABLE 1).5 Common reasons that dietary supplements are used include lowering blood glucose, lowering blood pressure, improving cholesterol, insulin resistance, neuropathy, and prevention of other diabetes-related complications.1,2 Dietary-supplement use has been found to be relatively prevalent among a subset of patients with diabetes, with just over half reporting use.8,9
Of patients taking dietary supplements, most reported taking two or three preparations, and they were generally unaware of the potential for interactions between dietary supplements and prescription medications. A small population of 150 patients with diabetes most commonly reported supplementing their diet with magnesium and herbs. Other common supplements included antioxidant vitamins, B-group vitamins, and omega-3 fatty acids. Dietary intake often showed deficiencies in calcium, magnesium, and potassium that were worse if the patient did not supplement the diet.9
Alpha-Lipoic Acid: Commonly referred to as ALA, alpha-lipoic acid is an antioxidant that helps the body convert energy into food. Unlike most dietary supplements used in diabetes, ALA is primarily used for peripheral neuropathy instead of blood glucose or A1C control.6 ALA does not prevent neuropathy, but it improves associated symptoms. It is unknown at this time whether it slows progression.7 While it is not commonly used to lower blood glucose, ALA may lower blood glucose, particularly in patients taking a medication with hypoglycemia as an adverse effect.7 This is a result of ALA increasing insulin sensitivity by 18% to 20% in patients with type 2 diabetes.10
Chromium: Patients with diabetes may be deficient in chromium, a trace element.10 The theorized benefit in type 2 diabetes is increased insulin sensitivity and improved glucose tolerance, although Brownley et al have contended that, based on mixed clinical-trial data, the belief that chromium helps glucose regulation is generally unjustified.10,11 Chromium is also thought to play a role in carbohydrate and lipid metabolism.12 Chromium is generally supplied as chromium picolinate.7 Patients are also interested in using chromium for weight loss, which is regulated by dopaminergic and serotonergic pathways.11 There are insulin receptors on these neuronal pathways, and insulin can decrease motivated feeding behavior.11
Although individual studies have shown benefits for A1C, glucose, and insulin levels, a meta-analysis by Althius et al found little effect on A1C, glucose, and insulin in patients with and without diabetes.13 The American Diabetes Association asserted that there is inconclusive evidence on the benefits of chromium supplementation in diabetes.14 Patients should be carefully evaluated before starting chromium for diabetes control, as it interacts with several medications. Medications that interact with chromium include antacids, beta-blockers, corticosteroids, H2 receptor antagonists, nicotinic acid, and nonsteroidal anti-inflammatory drugs.7
Cinnamon: Cinnamon is widely used by patients for both diabetes and hyperlipidemia.5 Cassia cinnamon, the variety contained in cinnamon supplements, is the same type of cinnamon as is used for cooking and baking.7 A meta-analysis found that dosages of 1 to 6 g per day of cassia cinnamon resulted in decreased fasting blood glucose and lipids, but not decreased A1C.15 However, a real-world study found a decrease of 0.83% in A1C over 3 months for 1 g per day.16 Another study used 2 g per day found only a reduced A1C of 0.36%, and a Cochrane review found insufficient evidence.17,18 While A1C does not appear to significantly improve with cinnamon use, cinnamon has produced blood glucose lowering of 18% to 29% in dosages of 1 to 6 g daily for 40 days. One g (approximately 1/2 teaspoon) continued to improve blood glucose levels for up to 20 days after discontinuation.7 The active ingredient in cinnamon is hydroxychalcone, which is thought to enhance the activity of insulin.7 Cinnamon is generally safe when used orally, but high doses pose a risk of liver damage because of high coumarin levels.19
Fenugreek: This dietary supplement is commonly used in cooking and smells like maple syrup.7 Small studies have shown that fenugreek may have a benefit in lowering blood glucose, likely through stimulation of insulin release.7 Fenugreek also contains fiber and slows gastric emptying to decrease carbohydrate digestion and absorption.7
Probiotics: Recent meta-analyses have evaluated the benefits of probiotics in type 2 diabetes. Results have been somewhat conflicting, but a meta-analysis by Yao et al and a separate meta-analysis by Sun and Buys found that probiotic supplementation benefited reduction of A1C and insulin resistance.20,21 Sun and Buys also found significant reductions in fasting blood glucose, while Yao et al did not.20,21 Yao et al also sought benefits in lipid metabolism, but no benefit was found.20 Benefits of probiotics are strain-specific, and pharmacists should recommend a probiotic species and strain previously found to have clinical benefit.
Probiotic species that appear to have benefit in multiple trials include Bifidobacterium breve, B longum, Lactobacillus acidophilus, L bulgaricus, L casei, L rhamnosus, and L sporogenes.20 A small study in gestational diabetes found that a probiotic mixture improved fasting blood glucose and insulin resistance and decreased weight gain.22 Improvements were not seen until after 6 weeks of continual use, and results need to be verified in larger clinical studies.22
B Vitamins: Several B vitamins are commonly used in type 2 diabetes, including thiamine (B1), pyridoxine (B6), biotin, folic acid (B9), and cobalamin (B12).23 Thiamine is commonly used for neuropathy associated with diabetes because many people with neuropathy have a thiamine deficiency.5 Thiamine is not well absorbed, and high doses are necessary.5 Thiamine has been found to be lower in patients with type 2 diabetes. Although it is typically used for neuropathy, thiamine has been found to decrease glucose and lipid levels in patients with diabetes.23 Patients with diabetes have also been found to have lower levels of the active form pyridoxine.23 A clinical trial did not find an association between folic acid, pyridoxine, cobalamin, and development of type 2 diabetes.21 However, a pyridoxine deficiency may negatively affect the progression of complications association with diabetes.23 Research on biotin in diabetes is limited, and most evidence is in combination with chromium.23
Prolonged use of metformin causes cobalamin malabsorption, which generally presents after 12 months of use.23 Cobalamin has been associated with reduced cognitive function in patients with diabetes, and it is used to correct deficiency versus treatment of diabetes.23 Folic acid has been shown to help improve glycemic control and insulin resistance. Metformin may be associated with folic acid deficiency, as well.23
Vitamin D: Liese et al demonstrated a correlation between geographical latitude and incidence of both type 1 and type 2 diabetes, and a seasonal variation in disease-state control has also been found. This suggests an inverse relationship between sunlight and diabetes incidence.24 Vitamin D receptors are present in pancreatic beta cells, and vitamin D is thought to decrease insulin resistance and increase insulin secretion.10,23 Deficiency of vitamin D has been associated with type 2 diabetes, likely owing to the deposition of vitamin D into fat, where it becomes less bioavailable.10
Vitamin D deficiency leads to decreased insulin sensitivity.10 Clinical trials of calcium and vitamin D supplementation found that vitamin D may decrease the risk of type 2 diabetes.23 When taken by patients with impaired glucose tolerance and type 2 diabetes, vitamin D may improve insulin secretion and glucose tolerance, resulting in lowered A1C levels.10 Although clinical trials are limited in assessing vitamin D as a modifier of type 2 diabetes risk, a 2007 meta-analysis suggested that vitamin D, when administered with calcium, may promote beta-cell function and insulin sensitivity.25
Counseling on Dietary Supplements
Patients with diabetes who take dietary supplements are generally unaware of the potential for them to interact with prescription medications.9 Further, only 16% sought advice from a healthcare provider about use of dietary supplements with their prescription medications, and only 8% of those patients consulted a pharmacist. Nearly all patients who consulted a healthcare provider consulted their physician.9 Use of dietary supplements in diabetes requires careful consideration because dietary deficiencies can lead to carbohydrate metabolism disturbances, and supplementation may increase risk of hypoglycemia.9 Patients should be cautioned about the potential risks and benefits of dietary supplements they are interested in using for diabetes management, including determining the existence of any evidence to support the product’s benefit in diabetes and any ADA statements or similar guidance for use. They should be advised of potential adverse effects and to monitor for them and report them if they occur.11 See TABLE 2.
It is critical to ensure that patients do not replace evidence-based prescription drugs with dietary supplements for management of their diabetes and associated complications. Dietary supplements should be used only as adjunctive treatment to FDA-approved prescription drugs.12 Patients should be instructed to report any serious health-related reactions or illnesses that may be associated with dietary-supplement use to the FDA. Patients should also be instructed to immediately stop using the product. The Safety Reporting Portal may be found at www.fda.gov/Food/DietarySupplements/ReportAdverseEvent.26 If the adverse effect is serious or life-threatening, the patient should be advise to seek immediate medical treatment.
Dietary supplements are commonly sought by patients with diabetes to manage their condition. Most supplements do not have adequate clinical data to support their use in type 2 diabetes, but in general, safety risks are not significant. Patients should be advised of clinical evidence, or lack thereof, when seeking dietary supplements for diabetes management, and any potential drug interactions with existing therapy should be evaluated. In addition, patients should be strongly advised that dietary supplements should never be used in place of prescription therapy for diabetes management, but as an adjunct to prescription therapy.
1. Centers for Disease Control and Prevention. Diabetes Quick Facts. https://www.cdc.gov/diabetes/basics/quick-facts.html. Accessed July 13, 2018.
2. Papaspurou M, Laschou VC, Partsiopoulou P, et al. Fears and health needs of patients with diabetes: a qualitative research in rural population. Med Arch. 2015;69(3):190-195.
3. American Diabetes Association. Herbs, supplements and alternative medicines. www.diabetes.org/living-with-diabetes/treatment-and-care/medication/other-treatments/herbs-supplements-and-alternative-medicines/. Accessed September 1, 2018.
4. Odegard PS, Janci MM, Foeppel MP, et al. Prevalence and correlates of dietary supplement use in individuals with diabetes mellitus at an academic medical center. Diabetes Educ. 2011;37(3):419-425.
5. Shane-McWhorter L. Dietary supplements for diabetes are decidedly popular: Help your patients decide. Diabetes Spectr. 2013;26(4):259-266.
6. U.S. Food & Drug Administration. Questions and answers on dietary supplements. www.fda.gov/food/dietarysupplements/usingdietarysupplements/ucm480069.htm#what_is. Accessed September 1, 2018.
7. Campbell AP. Diabetes and dietary supplements. Clin Diabetes. 2010;28(1):35-39.
8. Consumer Reports. 10 surprising dangers of vitamins and supplements: don’t assume they’re safe because they’re ‘all natural’. www.consumerreports.org/cro/magazine/2012/09/10-surprising-dangers-of-vitamins-and-supplements/index.htm. Accessed July 13, 2018.
9. Zablocka-Slowinska K, Dzielska E, Gryszkin I, Grajeta H. Dietary supplements during diabetes therapy and the potential risk of interactions. Adv Clin Exp Med. 2014;23(6):939-946.
10. Davi G, Santilli F, Patrono C. Nutraceuticals in diabetes and metabolic syndrome. Cardiovasc Ther. 2010;28:216-226.
11. Brownley KA, Boettlger CA, Young L, Cefalu WT. Dietary chromium supplementation for targeted treatment of diabetes patients with comorbid depression and binge eating. Med Hypotheses. 2015;85(10):45-48.
12. Saper RB, Eisenberg DM, Phillips RS. Common dietary supplements for weight loss. Am Fam Physician. 2004;70:1731-1738.
13. Althius MD, Jordan NE, Ludington EA, Wittes JT. Glucose and insulin responses to dietary chromium supplements: a meta-analysis. Am J Clin Nutr. 2002;76:148-155.
14. American Diabetes Association. Nutrition recommendations and interventions for diabetes (position statement). Diabetes Care. 2007;30:548-565.
15. Baker WL, Gutierrez-Williams G, White CM, et al. Effect of cinnamon on glucose control and lipid parameters. Diabetes Care. 2008;31:41-43.
16. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1c in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med. 2009;22:507-512.
17. Akilen R, Rsiami A, Devendra D, Robinson N. Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial. Diabet Med. 2010;27:1159-1167.
18. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database Syst Rev. 2012; 9:CD007170.
19. Natural Medicines. Therapeutic Research Center. Stockton, CA. https://naturalmedicines-therapeuticresearch-com.proxy200.nclive.org/about-us.aspx. Accessed August 1, 2018.
20. Yao K, Zeng L, He Q, et al. Effect on probiotics on glucose and lipid metabolism in type 2 diabetes mellitus: a meta-analysis of 12 randomized controlled trials. Med Sci Monit. 2017;23:3044-3053.
21. Sun J, Buys NJ. Glucose0 and glycaemic factor-lowering effects of probiotics on diabetes: a meta-analysis of randomized placebo-controlled trials. Br J Nutr. 2016;115(7):1167-1177.
22. Dolatkhah N, Hajifaraji M, Fatemeh Abbasalizadeh F, et al. Is there a value for probiotic supplements in gestational diabetes mellitus? A randomized clinical trial. J Health Popul Nutr. 2015;33:25.
23. Valdés-Ramos R, Laura GLA, Elina MCB, Donaji BAA. Vitamins and type 2 diabetes mellitus. Endocr Metab Disord Drug Targets. 2015;15:54-63.
24. Liese AD, Lawson A, Song HR, et al. Evaluating geographic variation in type 1 and type 2 diabetes mellitus incidence in youth for four U.S. regions. Health Place. 2010;16(3):547-556.
25. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92:2017-2029.
26. U.S. Food & Drug Administration. Dietary supplements—how to report a problem. www.fda.gov/Food/DietarySupplements/ReportAdverseEvent/. Accessed July 13, 2018.