Herb/Supplement Reference Design Sample Intervention Control Outcomes Evidence Direction Jadad Adverse Effects/Events Alpha-lipoic Acid Jacob S et al (1999) Blinding unclear; 4 parallel groups 74 Type 2; well-controlled on diet and/or OHA Alpha-lipoic-acid 600 mg/d vs. 1200mg/d vs. 1800 mg/d (Thioctacid, Asta Medica, Germany); for 4 wks Placebo pill Increase glucose uptake; trend decrease fasting insulin and improve insulin sensitivity; no change in FPG + 1 No side effects Branched Chain AA Mourier A et al (1997) Open-label; 4 parallel groups 24 Type 2; on diet and/or OHA Branched chain amino acid supplement containing leucine, isoleucine, valine (Paraphar Laboratories, France) +/- exercise training program; for 2 mos Placebo supplement (tricalcic phosphate and stearate of magnesium) No supplement effect on FBG, PPG, insulin, HgbA1C - 2 No side effects Carnitine (Acetyl-L-Carnitine) Giancaterini A et al (2000) Double-blind; Crossover; Short-term metabolic trial 18 Type 2; on diet, OHA, and/or insulin (switched to insulin during study) Intravenous infusion acetyl-L-camitine; 0.025mg/kg/min vs 0.1mg/kg/min; constant infusion during euglycemic-hyperinsulinemic clamp Saline infusion Increase glucose uptake, glucose storage; decrease insulin; no change in glucose or lipid oxidation ++ 4 Not reported Carnitine (L-Carnitine) Mingrone G et al (1999) Blinding unclear; Crossover; Short-term metabolic trial 15 Type 2; on diet and OHA (switched to insulin during study) L-Carnitine; 0.28 µmol/kg bw/min (Sigma Tau S.P.A., Italy);simultaneous infusion with euglycemic hyperinsulinemic clamp Saline infusion Increase glucose uptake, glucose oxidation, glucose storage, insulin sensitivity ++ 1 Not reported Carnitine Capaldo B et al (1991) Blinding unclear; Crossover; Short-term metabolic trial 9 Type 2 Carnitine; 1.7mmol/min; constant intravenous infusion with euglycemic hyperinsulinemic clamp Saline infusion Increase glucose uptake, insulin sensitivity ++ 1 Not reported Chromium Lee NA et al (1994) Double-blind; Crossover 30 Type 2; on diet, OHA, and/or insulin Chromium picolinate; 200µg/d (unspecified preparation); for 2 mos Placebo pill No change in FBG, HgbA1C - 4 No side effects Chromium Anderson R et al (1997) Double-blind; 3 parallel groups 180 Type 2; on diet, OHA, and/or TCM meds Chromium picolinate; 200µg/d vs. 1000µg/d ("Nutrition21," San Diego, CA); for 8 wks Matched placebo pill Decrease HgbA1C, fasting and postprandial insulin (both doses); decrease FBG and PPG (high dose) ++ 3 No side effects Chromium Bahijiri SM et al (2000) Double-blind; Multiple crossover 78 Type 2; on diet, OHA, and/or insulin Organic chromium (Brewer’s yeast capsule 23.3µg Cr/day) vs. Inorganic chromium (CrCl3 capsule 200µg Cr/day); for 8 wks Torula yeast capsule Decrease FPG, PPG, fructosamine (both Cr supplement types); no change in BMI ++ 4 No side effects Chromium Uusitupa MIJ et al (1992) Double-blind; 2 parallel groups 26 elderly with impaired glucose tolerance Chromium-rich yeast; 160µg/d in 4 pellets (unspecified preparation); for 6 mos Identical placebo pellets No change in FBG, PPG, postprandial insulin, HgbA1C, C-peptide, BMI - 3 Not reported Chromium Anderson RA et al (1991) Double-blind; Crossover 8 impaired glucose tolerance Chromium Chloride; 200µg/d (preparation unspecified); for 4 wks Placebo tablet Decrease PPG, postprandial insulin, glucagon ++ 2 Not reported Chromium Cefalu WT et al (1999) Double-blind; 2 parallel groups 29 obese nondiabetic at risk for Type 2 Chromium picolinate; 1000µg/d (preparation unspecified); for 8 mos Placebo Increase insulin sensitivity by FSIVGTT; no change in FPG, PPG, glycated Hgb, fructosamine, weight; trend decrease insulin + 2 No side effects Chromium Abraham AS et al (1992) Blinding unclear; 2 parallel groups 25 Type 2 with atherosclerotic disease; on diet and/or OHA Chromium chloride; 250µg/d in syrup (preparation unspecified); for 7–16 mos Placebo supplement in syrup No change in FBG - 2 No side effects, no effect on liver/renal function tests, CBC, chemistries Chromium, Zinc Anderson RA et al (2001) Double-blind; 4 parallel groups 110 Type 2; well-controlled on diet, OHA, and/or insulin Chromium pidolate 400µg/d vs. Zinc gluconate 30mg/d vs. Zn+Cr (Labcatal Pharmaceutical, France); for 6 mos Placebo pill Decrease in plasma thiobarbituric acid reactive substances (TBARS); no change in FPG, HgbA1C, insulin, weight, BMI (all supplement groups) - 2 No side effects Mg de Lourdes LM et al (1988) Double-blind; 3 parallel groups 128 Type 2, poorly controlled (with neuropathy and CAD) on diet and/or OHA Magnesium oxide; 20.7mmol/d vs. 41.4 mmol/d elemental Mg; for 30 d Placebo pill Decrease fructosamine (higher dose); no change in FBG, HgbA1C, BMI + 3 No side effects Mg Eibl NL et al (1995) Double-blind; 2 parallel groups 40 Type 2 with hypomagnesemia; well-controlled on diet and OHA Magnesium citrate; 30 mmol/d ("Magnosolv granulate," Asta Medica); for 3 mos Placebo pill No change in HgbA1C, FBG, PPG, insulin - 3 Exanthem (1), gastrointestinal pain (1) Mg Paolisso G et al (1992) Double-blind; Crossover 12 nondiabetic (elderly with insulin resistance) Magnesium pidolate; 4.5g/d Mg, ("Mag2," Lirca Synthelabo, Italy); for 4 wks Placebo pill Decrease FBG; increase postprandial insulin, glucose uptake, glucose oxidation; unclear C-peptide ++ 2 Not reported Mg Paolisso G et al (1994) Double-blind; Crossover 9 Type 2, elderly, nonobese; on diet alone Magnesium pidolate; 4.5g/d ("Mag2," Lirca Synthelabo, Italy); for 4 wks Placebo Improve insulin sensitivity and glucose oxidation during clamp; no change in FPG, C-peptide, glucagon, body weight + 2 Not reported Mg deValk HW et al (1998) Blinding unclear; 2 parallel groups 50 Type 2; all on diet and insulin Magnesium aspartate HCL; 15 mmol/d (Verla-Pharm, Germany); for 3 mos Placebo No change in FBG, HgbA1C, urine glucose - 2 No side effects Mg Paolisso G et al (1999) Open-label; Crossover 8 Type 2; on diet and OHA (diet alone during study) Magnesium; 2gm/d ("Mag2," Lirca Synthelabo, Italy); for 4 wks Placebo pill Decrease FPG, increase postprandial insulin ++ 1 Not reported Mg, Vit C Erikksson J et al (1995) Double-blind; Crossover 29 Type 1, 27 Type 2; on diet, OHA and/or insulin Magnesium (600 mg/day) vs. Ascorbic Acid (2g/day) water soluble tablets; for 90 d No treatment Decrease FBG, HgbA1C (Vit C in Type 2 only); otherwise no change - 3 No side effects Vanadium Cohen N et al (1995) Non-randomized; Single-blind; Crossover 6 Type 2; diet and/or OHA Vanadyl sulfate hydrate; 100mg/day (Spectrum Chemical, CA); for 3 wks Placebo capsule Decrease FBG, HgbA1C, hepatic glucose production; increase insulin-mediated glucose uptake, insulin sensitivity; trend decrease fructosamine; no change PPG and C-peptide ++ N/A 5/6 transient gastrointestinal discomfort; no effect on liver/kidney function Vanadium Halberstam M et al (1996) Non-randomized; Single-blind; Crossover 7 Type 2 Vanadyl sulfate hydrate; 100mg/day (Spectrum Chemical, CA); for 3 wks Placebo capsule Decrease FBG, HgbA1C, hepatic glucose output; increase insulin sensitivity; no change in insulin ++ N/A 7/7 transient gastrointestinal discomfort no effect liver/kidney function Vanadium Boden G et al (1996) Non-randomized; Single-blind; Crossover 8 Type 2; OHA and/or insulin Vanadyl sulfate; 100mg/d; for 4 wks Placebo capsule Decrease FBG, decrease hepatic glucose output during clamp ++ N/A 4/8 diarrhea; 1/8 nausea; 1/8 flatulence Vit E Reaven PD et al (1995) Double-blind; 2 parallel groups 21 Type 2 men; on diet and/or OHA Vitamin E; 1600 IU/d dl-alpha-tocopherol (Hoffman-LaRoche); for 10 wks Placebo pill No change in FBG, PPG, postprandial insulin, glycated Hgb, glycated albumin, glycated total plasma proteins, fructosamine; decrease susceptibility of LDL to oxidation - 4 No side effects Vit E Paolisso G et al (1993) Double-blind; Crossover 15 Type 2; well controlled on diet and OHA Vitamin E; 900 mg/d dl-alpha-tocopheryl acetate ("Ephynal," Roche, Italy); for 4 mos Sodium citrate placebo Decrease HgbA1C, FPG, PPG; no change in insulin, hepatic glucose output, glucose oxidation; increase total body glucose disposal and non-oxidative glucose metabolism ++ 3 No side effects Vit E Gomez-Perez FJ et al (1996) Double-blind; Crossover 53 DM (39 Type 2, 14 Type 1); poorly controlled on diet, OHA and/or insulin Vitamin E; 1200 mg/d (Searle de Mexico SA de CV): for 2 mos Placebo capsule No change in FBG, fructosamine, HgbA1C - 3 Not reported Vit E Paolisso G et al (1993) Double-blind; Crossover 25 Type 2; well controlled on diet and OHA Vitamin E; 900 mg/d d-alpha-tocopherol ("Ephynal," Roche, Italy); for 3 mos Placebo pill Decrease FPG, HgbA1C, PPG; no change in insulin ++ 3 No side effects; no effect on liver/renal function tests Vit E Ceriello A et al (1991) Single-blind; 3 parallel groups 30 "insulin-requiring DM"; on diet and insulin Vitamin E; 1200mg/d vs. 600 mg/d (unspecified preparation); for 2 mos Placebo Decrease Hgb A1C and glycosylated protein (dose related); no change in FPG or mean daily glucose ++ 1 Not reported Vit E Jain SK et al (1996) Non-randomized; Double-blind; 2 parallel groups 35 Type 1 Vitamin E; 100 IU/d; for 3 mos Placebo capsule Decrease glycated Hgb; no change FPG, insulin requirement + N/A Not reported

^* All trials are randomized unless otherwise specified in the "Design" column. -, no outcome measures positive; +, at least one outcome measure positive; ++, >50% of outcome measures positive. FBG, fasting blood glucose; FSIVGTT, frequently sampled intravenous glucose tolerance test; PPG, postprandial glucose; OHA, oral hypoglycemic agent.

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