Nutraceuticallaboratory Test Interactions

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At this point in time, fewer than 1 of 10 nutraceuticals appear to have interactions with laboratory tests. This is probably largely because these supplements are generally safe but also because there is no required screening process for all nutraceuticals prior to making them available to consumers. Yet, when an interaction does arise, the result can take the form of an actual alteration of laboratory values resulting from changes in biochemical metabolism in vivo or false laboratory values caused by interference with a given laboratory technique. The tendency for certain nutraceuticals to be used for addressing specific conditions can guide a health provider in determining the potential presence of a culprit that may alter laboratory values. This chapter covers only a select group of common nutraceuticals and botanicals.

Table 39-1. Natural Medicine-Laboratory Test Interaction Summary

Natural Medicine

Common Names

Reasons for Use

Possible Effects on Laboratory Values

Alpha-lipoic acid a-lipoic acid, ALA, lipoic acid, thioctacid, thioctan

Androstene- Andro, dione androstene

Beta-glucan

Boron b-glucan, beta-glycan, gifolan, schizophyllan

Borate, boric acid, sodium borate

Glucosamine sulfate

Antioxidant; prevent diabetes, retinopathy, cataracts, or glaucoma; support patients with HIV, Wilson's disease, or lactic acidosis resulting from altered metabolism

Replace low endogenous levels or lowered androgen levels; increase athletic performance; enhance exercise endurance; decrease recuperative time; support sexual function

D-Glucosamine, glucosamine sulphate

(British spelling)

Support patients with high cholesterol, cancer, HIV, diabetes, allergies, and other conditions Promote bone health; treat OA; enhance mental functioning; increase muscle mass, (illustrates benefits of using trace minerals therapeutically) Support patients with OA and other joint conditions, including TMJ disease

Blood glucose: may lower serum glucose levels in patients with type 2 diabetes by reducing insulin resistance and enhanced glucose utilization Glycosylated hemoglobin: may decrease T-helper= T-suppressor ratio: improves ratio of T-helper cells relative to T-suppressor cells HDL: lowers HDL levels Estrone, estradiol, testosterone, dihydrotestosterone; elevates estrone, free testosterone, dihydrotestosterone, and estradiol levels Nandrolone: urine tests positive for nandrolone marker because of contamination with 19-norandrostenedione Testosterone: free and total testosterone levels may become elevated initially but may then normalize WBC counts: WBC counts may be elevated

Estrogen: theoretically, may elevate estrogen levels Bone-mineral density:

increases in female athletes Phosphorus: decreases serum phosphorus Glucose: may elevate blood glucose Insulin: potential ability to increase insulin level

(continued)

Table 39-1. (Continued)

Natural Common Possible Effects on

Medicine Names Reasons for Use Laboratory Values

N-acetyl- NAC Anti-inflammatory; cysteine mucolytic;

increases levels of glutathione

Vitamin C Antioxidant;

maintaining normal immune function for infections, cancer, and allergies; a cofactor for several biochemical pathways

Calcium Bone mineral density

Prothrombin time: decrease in prothrombin time. Blood pressure: NAC=nitroglycerin combination can lower blood pressure and reduce blood pressure readings Salicylate: falsely low serum salicylate test results Chloride: false-positive serum chloride test results Creatinine: falsely low serum creatinine test results Free cysteine: increases free cysteine plasma concentrations Ketones: on urinary dipstick tests, NAC can cause false-positive urine ketones Lipoprotein A: might reduce serum lipoprotein A

concentrations Lithium: very high serum NAC concentrations might cause falsely low serum lithium test results ALT= AST: increases AST and ALT

concentrations Acetaminophen: false-negative urine results AST: false increase in results of serum tests Bilirubin: false increase in serum test Theophylline: false decrease in serum assay Carbamazepine (Tegretol): falsely increased serum assay results LDH: false decrease in test results Creatinine: false increase in serum creatinine or urine test results Calcium=sodium: increase in urinary calcium and a decrease in urinary sodium Glucose: false increases in urine test results Uric acid: decrease in serum uric acid concentrations HDL-2: lowers HDL-2 levels Iron: increase measures of iron status, such as serum iron and ferritin Vitamin B12: false decrease in vitamin B12 levels Occult stool: false-negative guaiac results Bone mineral density: may increase Plasma 11-hydroxycorticosteroid: may increase Urinary 17-hydroxycorticosteroid: may decrease Gastrin: may increase Glucose: may decrease Uptake of I-131: may decrease Insulin: may increase plasma insulin Lipase: may falsely decrease test results Magnesium: may falsely decrease test results

Alpha-Lipoic Acid

Alpha-lipoic acid is generally considered to be a fairly targeted nutrient that is used to achieve specific health goals.

Glucose level—A study, conducted by the Department of Internal Medicine, in Frankfurt, Germany, examined the effect of alpha-lipoic acid, a cofactor of the pyruvate dehydrogenase complex, on insulin sensitivity and glucose effectiveness. The subjects included 10 lean and 10 obese patients with type 2 diabetes and 10 lean and 10 obese healthy controls. Insulin sensitivity and glucose effectiveness were measured after oral glucose loading. A modified, frequently sampled, intravenous (IV) glucose tolerance test was performed after oral treatment with 600 mg of alpha-lipoic acid, twice per day, for four weeks. alpha-lipoic acid was associated with increased glucose effectiveness in both groups of patients with diabetes. Higher insulin sensitivity and lower fasting glucose levels were noted in only the lean patients with diabetes. In addition, lactate and pyruvate, before and after glucose loading, were approximately 45% lower in both the lean and obese patients with diabetes.1 Glycosylated hemoglobin level—No effect has been observed, although daily glucose levels may be lower on average in patients who take this supplement.2,3 A seven-month, multicenter, randomized controlled trial examined the effects of alpha-lipoic acid on polyneuropathy in patients with diabetes. The study involved 509 outpatients who were assigned randomly for six months to sequential treatment with 600 mg of alpha-lipoic acid per day, IV, for three weeks, followed by 600 mg of alpha-lipoic acid three times per day for six months. A placebo group received 600 mg of alpha-lipoic acid for three weeks, followed by a placebo, three per day for six months. There was no overt effect on glycosylated hemoglobin. The researchers concluded that there was a favorable effect on reducing diabetic neuropathy without adverse reactions.3

T-helper cell=T-suppressor cell ratio—Alpha-lipoic acid may improve the T-helper= T-suppressor ratio in patients who are infected with human immunodeficiency virus (HIV).4

Triiodothyronine (T3)—In experimental models, when alpha-lipoic acid was added to T4 supplementation, there was a decrease of T3 production by 22%-56%.5

Androstenedione

Whenever a hormonal intervention is utilized to produce altered physiologic activity or to alter biochemical processes, a myriad of potential effects can arise. All too often, patients will take over-the-counter hormones, not realizing that they are supplements that should be listed on patient intake forms as such or not telling providers about such use. Although this supplement is taken by many patients to enhance wellness, androstenedione can actually alter important cardiovascular indices.

High-density lipoprotein—Androstenedione may suppress high-density lipoprotein (HDL) levels.6 Young men who consumed 100 mg of androstenedione three times per day for 28 days experienced a 10% decrease in HDL level.7 Estrone and estradiol—Because androstenedione is a precursor of estrone, androstenedione supplements may cause elevations of estrone and estradiol levels.6,7 The previously described 12-week study of the adverse effects of androstenedione on cholesterol produced a significant increase in the aromatization by-products estrone and estradiol.6 In a double-blind, randomized, 28-day study of 55 men, 28 subjects were given 100 mg of androstenedione, three times per day, and 27 were given a placebo. Results of serum readings reflected an increase of androstenedione (300%), free testosterone (45%), dihydrotestosterone (83%), and estradiol (68%).7 Nandrolone—Patients' urine may test positive for the presence of nandrolone as a result of trace contamination of androstenedione with 19-norandrostenedione.8 Nandrolone is an anabolic steroid that resembles testosterone in chemical structure and biologic activity. It is the subject of concern for athletic oversight committees, which test for illicit use by measuring the urine levels of its metabolite, 19-norandrostenedione. Trace contamination of androstenedione with 19-norandrostenedione could result in the unjust accusation that an athlete has used steroids illicitly. As noted in an insightful paper in the Journal of the American Medical Association,8 it is important that consumers be advised to buy supplements from reputable manufacturers who provide certificates of analysis.

The study discussed in this paper involved 41 healthy men, ages 20-44 who took either 100 mg or 300 mg per day of androstenedione for seven days. All subjects were treated with androstenedione containing 19-norandrostenedione. The authors proved that, if androstenedione that was sold over the counter (OTC) contained 19-norandrostenedione, the nandrolone marker was found in the subjects' urine. This led the researchers to test seven OTC products randomly for the presence of 19-norandrostenedione. Of seven brands tested, one contained no androstenedione, one contained 10 mg of testosterone, and four more contained 90% or less of the amount stated on the product labels. The authors concluded that trace contamination of androstenedione with 19-norandrostenedione is sufficient to cause positive urine results for the presence of 19-androstenedione.

Patients' urine may test positive for the presence of nandrolone as a result of trace contamination of androstenedione with 19-norandrostenedione.

Testosterone—Free and total testosterone levels can become elevated, particularly in the first two months of use, although testosterone levels may begin to normalize over the course of time for many patients. This effect is the result of the precursor nature of androstenedione for testosterone production.6

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