Dietary Supplementation in the Diabetic Patient

OTC dietary supplements haveinundated American culture:their ads appear on television,in magazines, and on the Internet. Theinherent ambiguity of dietary supplementscan put the pharmacist in anuncomfortable position when he orshe is asked across the counter, "Is thisproduct safe for me to take?" Claimsfor supplements can be vague and theirrisks can be undetermined, and, whenpatients' preexisting disease states areconsidered, uncertainty is bound toarise. Most studies of vitamin, mineral,herbal, or other alternative supplementshave been inconclusive. Moreresearch needs to be done before anyclinician can fully advocate their use.

Although evidence of beneficialeffects may be lacking, however, mostsupplements have been found to besafe for patients with diabetes. Fourgeneral categories with potential usefor diabetic patients are vitamins, minerals,supplements, and herbs.

Vitamins

Supplemental folic acid is promotedto help prevent macrovascular andmicrovascular complications of diabetesthrough its role in the regulationof blood homocysteine levels. Increasedlevels of homocysteine are associatedwith a greater risk of cardiovasculardisease and mortality, especiallyin diabetic patients.¹ Whereas folic acidsupplementation poses minimal riskfor toxicity, its significance in cardiovascularhealth is undetermined.²

Niacin therapy is not a new strategyin the treatment of hypercholesterolemia.Its place in therapy for thediabetic patient, however, is growing.In a recent study, patients takingniacin 500 mg 3 times a day in combinationwith pravastatin showed a significantdrop in low-density lipoproteincholesterol, when compared withpatients taking pravastatin alone.³

High doses of pantethine, a derivativeof pantothenic acid, may aid inlowering cholesterol and triglycerides.Its mechanism is believed to involve 3-hydroxy-3-methylglutaryl coenzyme Areductase inhibition.⁴Vitamin E has not proven to be effectivein producing positive outcomes indiabetic patients, particularly in preventingcardiovascular complications.

Vitamin E given with nicotinic acid,however, in patients with new-onsettype 1 diabetes, may lead to preventionof beta-cell loss. Doses generallyrange from 400 to 800 mg per day.^5,6

Vitamin C deficiency may be moreprevalent in diabetic patients than innondiabetic patients, although findingsare inconclusive.^7,8

Some correlation between vitaminD deficiency, insulin resistance, andbeta-cell dysfunction exists, even inglucose-tolerant patients.⁹ Vitamin Dmay protect against autoimmuneattack on the insulin-producing cells.

Minerals

Chromium, an element required forglucose maintenance, is promoted tobenefit patients with glucose intoleranceand insulin insensitivity.^10,11 Deficiencyin chromium typically presentsas increased blood glucose levels,glucosuria, weight loss, elevated plasmafree fatty acid concentrations,neuropathy, and altered nitrogenmetabolism. One study of patientswith gestational diabetes showedimproved postprandial glucose levelswith supplementation of 4 to 8mcg/kg/day of chromium. When themineral was administered in highdoses (1000 mcg/day) to type 2 diabeticpatients, glycemic controlimproved. Interestingly, a decrease intotal cholesterol was noted as well.¹⁰Despite these results, most cliniciansagree that further research is requiredto establish the significance ofchromium supplementation in thediabetic patient.²

Copper supplementation is promotedto enhance such functions as bloodcell maturation, iron transport, cholesterolmetabolism, and myocardialcontractility. It does not appear, however,to play a role in either type 1 ortype 2 diabetes.¹²

Iron, which can act as a catalyst offree radical particles, has been suggestedto influence the onset of diabetes. Aprospective, randomized 4-year studyin Finland found that men withgreater iron stores were 2.5 times morelikely to develop type 2 diabetes thanmen with lower iron stores.¹³

Low plasma magnesium concentrationsoften are found in diabeticpatients. This magnesium deficiencymay exacerbate insulin resistanceand put diabetics at risk for cardiovascularcomplications.¹⁴

Supplements

Conjugated linoleic acid (CLA) supplementationcould be beneficial totype 2 diabetics in losing weight, andit appears safe. The average range is 1to 5 g/day of CLA.¹⁵

Fiber is an important factor in reducingthe risk of diabetes. The combinationof high glycemic load and a lowcereal fiber content further increasedthe risk of diabetes in one study of morethan 65,000 US women.¹⁶ No RecommendedDaily Allowance for dietaryfiber exists, although between 20 and35 g of fiber a day is suggested.¹⁷

Alpha-lipoic acid (ALA) is believedto help prevent cellular damage inneural and renal tissue in diabeticpatients through its antioxidant properties.ALA has been used for decadesin Germany for the treatment of diabeticneuropathy. Recent studies,however, have had mixed results:moderate improvement or noimprovement at all. ALA also mayplay a role in the prevention of renaldamage. In a prospective, nonrandomizedstudy, patients not usingALA were shown to have a significantincrease in urinary albumin concentration;however, further investigationis warranted. ALA also has beenstudied in glucose uptake: 600 mgtwice a day was shown to increase glucosesensitivity in lean and obesepatients with type 2 diabetes.¹⁸

Coenzyme Q10 (CoQ10) is anantioxidant agent promoted toimprove endothelial dysfunction ofthe brachial artery in type 2 diabeticpatients with dyslipidemia. Supplementationin patients deficient ofCoQ10 also is suggested to improveglycemic control.¹⁹

Herbs

American ginseng has shown someof the best evidence of benefits inpatients. It appears to decrease postprandialglycemia in healthy nondiabeticpatients and to lower hemoglobinA_1C levels.²⁰ Three grams per day isthe standard dose of American ginseng.Patients wishing to try ginsengshould be warned of the potentialinteractions between the herb andother drugs. Asian ginseng maydecrease warfarin activity, and ginsengmay increase the effects of caffeine andother stimulants. Ginseng also maycause a reduction in the dose of insulinor oral hypoglycemic agents. In addition,it can interact with digoxin andnonsteroidal anti-inflammatory drugs.

Ginseng may cause mild irritabilityand excitation, insomnia, depression,headache, hypertension, and possibleweight loss. Ginseng should be avoidedin patients with hypertension orcardiovascular disease.

L-carnitine, which influences freefatty acid and glucose oxidation, hasbeen studied in patients with diabetes.Trials show that intravenous carnitineadministration can possibly affectinsulin sensitivity as well as enhanceglucose uptake and storage.²¹

Other herbal supplements that havepotential benefits in treating diabeticpatients include Coccinia indica, Aloevera, vanadium, Momordica charantia,and Nopal. These agents have shownpromise, but more conclusive data areneeded to show benefits.¹⁰

Conclusion

Recommending a dietary supplementis a challenging task for any clinician.Diabetic patients present a morecomplicated picture, as their healthmay be compromised or they may havecomorbidities. Especially in light ofminimal clinical testing and data, thepharmacist must weigh the potentialbenefits and risks of dietary supplementsin the diabetic population.

Dr. Schott is a pharmacist with Stop andShop, Wallingford, Conn. Dr. Holmberg isa pharmacist with Phoenix Indian MedicalCenter, Phoenix, Ariz.

For a list of references, send astamped, self-addressed envelope to:References Department, Attn. A. Stahl,Pharmacy Times, 241 Forsgate Drive,Jamesburg, NJ 08831; or send ane-mail request to: astahl@mwc.com.