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Hierbas y Dietas para El Control de La Diabetes
Hierbas y Dietas para El Control de La Diabetes
D
iabetes is a predominant public lar disease. With increasing rates of child- systems of healing such as traditional
health concern, affecting ⬃16 mil- hood and adult obesity, diabetes is likely Chinese medicine (TCM) (19 –30).
lion persons in the U.S. The disease to become even more prevalent over the Most of the literature, however, has
causes substantial morbidity, mortality, coming decade (1). focused on herbs or other dietary supple-
and long-term complications and remains In response to the increasing use of ments. This finding parallels results from
an important risk factor for cardiovascu- complementary and alternative medicine prevalence surveys that report herbal
● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● remedies or other dietary supplements
From the 1Division for Research and Education in Complementary and Integrative Medical Therapies, taken by mouth to be consistently among
Harvard Medical School, Boston, Massachusetts; and the 2Division of General Medicine and Primary Care, the top CAM therapies used, regardless of
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. the sample surveyed (5,6,8,9,31).
Address correspondence and reprint requests to Gloria Y. Yeh, MD, Harvard Osher Institute, 401 Park Dr.,
Ste. 22A, Boston, MA 02215. E-mail: gyeh@caregroup.harvard.edu.
Plant derivatives with purported hy-
Received for publication 30 October 2002 and accepted in revised form 13 January 2003. poglycemic properties have been used in
Additional information for this article can be found in an online appendix at http://care. folk medicine and traditional healing sys-
diabetesjournals.org. tems around the world (e.g., Native
Abbreviations: CAM, complementary and alternative medicine; GTT, glucose tolerance test; RCT, ran-
domized controlled trial; TCM, Traditional Chinese medicine.
American Indian, Jewish [32], Chinese
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion [20], East Indian, Mexican). Many mod-
factors for many substances. ern pharmaceuticals used in conventional
1278
Evidence Adverse Effects/
Herb/Supplement Reference Design Sample Intervention Control Outcomes Direction Jadad Events
Allium sativum Sitprija S et al Double-blind; 2 33 Type 2; diet Garlic; 700 mg/d Placebo No change in FBG, – 2 No side effects; no
(Garlic) (1987) parallel groups alone (preparation PPG; insulin effect on liver
unspecified); for 4 wks function
Aloe vera Bunyapraphatsara Non-randomized; 76 Type 2; Aloe vera Linn. 80% Placebo juice Decrease FBG ⫹ N/A No effects on liver/
N et al (1996) Single-blind; 2 uncontrolled juice; 1 tbsp BID kidney function
parallel groups on OHA (prepared by Faculty
of Pharmacy, Mahidol
University, Thailand);
for 42 d
Aloe vera Yongchaiyudha S Non-randomized; 40 Type 2; Aloe vera Linn. 80% Placebo juice Decrease FBG ⫹ N/A 1/40 ketosis (group
Review of herbs/vitamins in diabetes
Artocarpus Fernando MR et Non-randomized; 10 Type 2; no Artocarpus heterophyllus; Distilled water Decrease PPG ⫹ N/A Not reported
heterophyllus al (1991)† Open-label; diabetes 200mg fresh leaves
Crossover; medication boiled decoction;
Short-term single experimental
metabolic trial dose prior to GTT
Asteracanthus Fernando MR et Non-randomized; 10 Type 2; no Asteracanthus longifolia; Distilled water Decrease PPG ⫹ N/A Not reported
longifolia al (1991)† Open-label; diabetes 100mg fresh leaves
Crossover; medication boiled decoction;
Short-term single experimental
metabolic trial dose prior to GTT
Bauhinia forficata Russo EMK et al Double-blind; 16 Type 2; diet Bauhinia forficata tea; Placebo herb tea No change in FBG, ⫺ 3 No side effects; no
(1990) Crossover and/or OHA 3g/d (1g individual tea (sape, Imperata HgbA1C, insulin effect on liver/
bags from dried brasiliensis) kidney function
leaves); for 8 wks
Coccinia indica Azad Khan AK et Double-blind; 2 32 Type 2; Coccinia indica leaf; 1800 Placebo tablet Decrease FBG, PPG ⫹⫹ 4 No side effects; no
al (1979) parallel groups uncontrolled or mg/d (freeze-dried effect on liver/
untreated powder from fresh kidney function
leaves in tablets); for 6
wks
Coccinia indica Kamble SM et al Non-randomized; 70 Type 2; other Coccinia indica; 6g/d No treatment; OHA Decrease FBG, PPG ⫹⫹ N/A Not reported
(1996) Open-label; 3 medications (dried pellets from (similar to OHA)
parallel groups unclear fresh leaves); for 12
wks
Ficus carica (Fig leaf) Serraclara A et al Open-label; 10 Type 1; diet Fig leaf tea; 13g/d leaf Bitter commercial tea Decrease PPG, ⫹ 2 No side effects
(1998) Crossover and insulin decoction; for 4 wks blend insulin
requirement; no
change in FPG,
C peptide,
HgbA1C
Ginseng Sotaniemi EA et Double-blind; 3 36 Type 2; newly Ginseng; 100mg/d vs. Placebo tablet Decrease FBG, ⫹ 3 No side effects
(Unspecified) al (1995) parallel groups diagnosed; diet 200mg/d (tablet HgbA1C
alone preparation Dansk (200mg); no
Droge, Copenhagen); change in BG,
for 8 wks insulin, C-
peptide during
Gymnema sylvestre Baskaran K et al Non-randomized; 47 Type 2; all on Gymnema sylvestre No GS4 treatment Decrease FBG, ⫹⫹ N/A Not reported
(1990) Open-label; 2 OHA extract, GS4; 400 mg/d HgbA1C,
parallel groups capsule; for 18–20 mos glycosylated
plasma protein,
conventional
medication, urine
glucose; increase
insulin
Gymnema sylvestre Shanmugasundaram Non-randomized; 64 Type 1; all on Gymnema sylvestre No GS4 treatment Decrease FBG, ⫹⫹ N/A No side effects
ERB et al Open-label; 2 insulin extract, GS4; 400 mg/d HgbA1C,
(1990) parallel groups capsule; for 2–30 mos glycosylated
plasma protein,
insulin
requirement,
urine glucose;
increase C-
peptide
Momordica charantia Welhinda J et al Non-randomized; 18 Type 2; newly Momordica charantia Distilled water Decrease PPG ⫹ N/A Not reported
(1986) Open-label; diagnosed juice; homemade
Crossover; preparation (dose
Short-term unspecified); single
metabolic trial experimental dose
prior to GTT
Momordica charantia, Baldwa VS et al Non-randomized; 9 DM (?6 Type 1, Momordica charantia Placebo injection Decrease FBG ⫹ N/A No hyper-sensitivity
V-insulin (1977) Blinding 3 Type 2); all vegetable insulin (unspecified) reactions
unclear; 2 on insulin/OHA (purified protein
parallel stopped during extract); single severity
groups; Short- study dependent
term metabolic experimental dose
trial (subcutaneous)
Myrcia uniflora Russo EMK et al Double-blind; 18 Type 2; on diet Myrcia uniflora tea; 3g/d Placebo herb tea No change in FBG, ⫺ 3 No side effects; no
(1990) Crossover and/or OHA (1g individual tea bags (sape, Imperata HgbA1C; effect on liver/
from dried leaves); for brasiliensis) decrease insulin kidney function
8 wks
Ocimum sanctum Agrawal P et al Single-blind; 40 Type 2; on diet Ocimum album fresh leaf; Fresh spinach leaf Decrease FBG, PPG, ⫹⫹ 2 No side effects
(Holy basil) (1996) Crossover and/or OHA 2.5g powder; for 4 wks powder urine glucose
Yeh and Associates
1279
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Opuntia streptacantha Frati AC et al Open-label; 14 Type 2; diet Grilled nopal stems; 400ml H2O Decrease glucose, ⫹⫹ 1 Not reported
(Nopal) (1990) Crossover; and/or OHA 500g; single insulin
1280
Short-term (diet alone dur- experimental dose
metabolic trial ing study)
Opuntia streptacantha Frati-Munari AC Non-randomized; 32 Type 2; OHA Fresh nopal stems, Water; broiled Decrease FBG, ⫹⫹ N/A Not reported
(Nopal) et al (1988) Open-label; stopped during broiled; 500g crude zucchini squash insulin
Crossover; study weight; single
Short-term experimental dose
metabolic trial
Silymarin (Milk Velussi M et al Open-label; 2 60 Type 2 with Silymarin; 600mg/d No treatment Decrease FBG, ⫹⫹ 2 No side effects
Thistle) (1997) parallel groups cirrhosis; diet (“Legalon” formulation, mean BG, urine
and insulin IBI Lorenzini, Milan); glucose,
for 12 mos HgbA1C, fasting
insulin, insulin
requirement, C
peptide
Review of herbs/vitamins in diabetes
Trigonella foenum Sharma RD et al Blinding unclear; 15 Type 2; diet Defatted fenugreek seed No treatment Decrease FBG, PPG, ⫹⫹ 1 Not reported
(Fenugreek) (1990) Crossover and OHA (dose powder; 100g/day in postprandial
decreased 20% unleavened bread; for insulin, urine
during study) 10 d glucose
Trigonella foenum Sharma RD et al Blinding unclear; 5 Type 2; diet and Defatted fenugreek seed No treatment Decrease FBG, PPG, ⫹⫹ 1 Not reported
(Fenugreek) (1990) Crossover OHA (dose powder; 100g/day in urine glucose,
decreased 20% unleavened bread; for insulin
during study) 20d
Trigonella foenum Sharma RD et al Blinding unclear; 10 Type 1; diet Defatted debitterised No treatment Decrease FBG, PPG, ⫹⫹ 1 Not reported
(Fenugreek) (1990) Crossover and insulin fenugreek seed urine glucose; no
(dose decreased powder; 100g/d in change body
during study) unleavened bread; for weight, insulin
10d
Trigonella foenum Madar Z et al Non-randomized; 21 Type 2 Fenugreek seed powder; No treatment Decrease PPG; no ⫹ N/A No side effects
(Fenugreek) (1988) Open-label; 15g in water; single change in insulin
Crossover; experimental dose with
Short-term meal tolerance test
metabolic trial
*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; PPG, postprandial glucose; OHA, oral hypoglycemic agent. †Fernando MR, Wickramasinghe N, Thabrew MI, Ariyananda PL, Karunanayake EH: Effect of Artocarpus heterophyllus and
Asteracantha longifolia on glucose tolerance in normal human subjects and in maturity-onset diabetic patients. J Ethnopharmacol 31:277–277, 1991
(48 –51).
ture research.
METHODS
with diabetes.
of increasing interest (35).
*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
Diarrhea (1), dry mouth
Adverse Effects/Events
Minor gastrointestinal
hypoglycemia (10)
search to herbs and supplements for gly-
hypoglycemia (9)
OHA treatment;
cemic control and symptoms of hypergly-
discomfort (1)
OHA⫹TCM
No side effects
No side effects
vertigo (1), cemia. We excluded trials that primarily
Not reported
examined diabetic complications such as
neuropathy, nephropathy, or retinopa-
thy. We included studies in subjects with
impaired glucose tolerance or those spe-
Jadad
N/A
cifically at risk for diabetes (e.g., older,
3
2
sedentary, obese individuals with a family
history of diabetes). As supporting evi-
Direction
Evidence
⫹⫹
dence, we also examined studies of glyce-
⫹
⫺
mic control in healthy volunteers. To
assess quality of RCTs, we employed the
FBG, PPG, or insulin
No change in HgbA1C,
PPG, with synergistic
No change in PPG,
difference from
treatments; no
Outcomes
fructosamine,
effect of both
in weight
description of study withdrawals or drop-
HgbA1C
HgbA1C
control
with Chinese
green tea,
treatment
American Diabetes Association evidence
capsule;
tablet
No herb
grading system for clinical practice rec-
seed
Ramulus Cinnamomum,
membranaceus, 120mg
Scrophularie, Radix
Intervention
Rehmanniae, Radix
untreated; on
diagnosed or
40 Type 2; on
Sample
diet alone
diet alone
or insulin
Data synthesis
148 Type 2
parallel groups
parallel groups
parallel groups
Non-randomized;
Open-label; 2
Double-blind; 4
Open-label; 2
Crossover
Design
Ryan EA et al
Reference
Vray M et al
Hale PJ et al
(1989)
(1995)
(2000)
(2001)
herb combina-
herb combina-
herb combina-
Tibetan Medicine
tion
tion
1282
Evidence Adverse Effects/
Herb/Supplement Reference Design Sample Intervention Control Outcomes Direction Jadad Events
Alpha-lipoic Acid Jacob S et al Blinding unclear; 4 74 Type 2; well-controlled Alpha-lipoic-acid 600 mg/d Placebo pill Increase glucose uptake; ⫹ 1 No side effects
(1999) parallel groups on diet and/or OHA vs. 1200mg/d vs. 1800 trend decrease fasting
mg/d (Thioctacid, Asta insulin and improve
Medica, Germany); for 4 insulin sensitivity; no
wks change in FPG
Branched Chain AA Mourier A et al Open-label; 4 24 Type 2; on diet and/or Branched chain amino acid Placebo supplement No supplement effect on ⫺ 2 No side effects
(1997) parallel groups OHA supplement containing (tricalcic FBG, PPG, insulin,
leucine, isoleucine, valine phosphate and HgbA1C
(Paraphar Laboratories, stearate of
France) ⫹/⫺ exercise magnesium)
training program; for 2 mos
Review of herbs/vitamins in diabetes
Carnitine (Acetyl-L- Giancaterini A et Double-blind; 18 Type 2; on diet, OHA, Intravenous infusion acetyl-L- Saline infusion Increase glucose uptake, ⫹⫹ 4 Not reported
Carnitine) al (2000) Crossover; and/or insulin (switched camitine; 0.025mg/kg/min glucose storage;
Short-term to insulin during study) vs 0.1mg/kg/min; constant decrease insulin; no
metabolic trial infusion during change in glucose or
euglycemic- lipid oxidation
hyperinsulinemic clamp
Carnitine (L-Carnitine) Mingrone G et al Blinding unclear; 15 Type 2; on diet and L-Carnitine; 0.28 mol/kg Saline infusion Increase glucose uptake, ⫹⫹ 1 Not reported
(1999) Crossover; OHA (switched to bw/min (Sigma Tau S.P.A., glucose oxidation,
Short-term insulin during study) Italy);simultaneous glucose storage,
metabolic trial infusion with euglycemic insulin sensitivity
hyperinsulinemic clamp
Carnitine Capaldo B et al Blinding unclear; 9 Type 2 Carnitine; 1.7mmol/min; Saline infusion Increase glucose uptake, ⫹⫹ 1 Not reported
(1991) Crossover; constant intravenous insulin sensitivity
Short-term infusion with euglycemic
metabolic trial hyperinsulinemic clamp
Chromium Lee NA et al Double-blind; 30 Type 2; on diet, OHA, Chromium picolinate; 200g/ Placebo pill No change in FBG, ⫺ 4 No side effects
(1994) Crossover and/or insulin d (unspecified HgbA1C
preparation); for 2 mos
Chromium Anderson R et al Double-blind; 3 180 Type 2; on diet, OHA, Chromium picolinate; 200g/ Matched placebo Decrease HgbA1C, ⫹⫹ 3 No side effects
(1997) parallel groups and/or TCM meds d vs. 1000g/d pill fasting and
(“Nutrition21,” San Diego, postprandial insulin
CA); for 8 wks (both doses);
decrease FBG and
PPG (high dose)
Chromium Bahijiri SM et al Double-blind; 78 Type 2; on diet, OHA, Organic chromium (Brewer’s Torula yeast capsule Decrease FPG, PPG, ⫹⫹ 4 No side effects
(2000) Multiple and/or insulin yeast capsule 23.3g Cr/ fructosamine (both
crossover day) vs. Inorganic Cr supplement
chromium (CrCl3 capsule types); no change in
200g Cr/day); for 8 wks BMI
Chromium Uusitupa MIJ et al Double-blind; 2 26 elderly with impaired Chromium-rich yeast; 160g/ Identical placebo No change in FBG, PPG, ⫺ 3 Not reported
(1992) parallel groups glucose tolerance d in 4 pellets (unspecified pellets postprandial insulin,
preparation); for 6 mos HgbA1C, C-peptide,
BMI
Chromium Anderson RA et al Double-blind; 8 impaired glucose Chromium Chloride; 200g/ Placebo tablet Decrease PPG, ⫹⫹ 2 Not reported
(1991) Crossover tolerance d (preparation postprandial insulin,
unspecified); for 4 wks glucagon
Chromium Cefalu WT et al Double-blind; 2 29 obese nondiabetic at risk Chromium picolinate; Placebo Increase insulin ⫹ 2 No side effects
(1999) parallel groups for Type 2 1000g/d (preparation sensitivity by
unspecified); for 8 mos FSIVGTT; no change
in FPG, PPG,
glycated Hgb,
fructosamine, weight;
trend decrease insulin
Mg de Lourdes LM et Double-blind; 3 128 Type 2, poorly Magnesium oxide; 20.7mmol/ Placebo pill Decrease fructosamine ⫹ 3 No side effects
al (1988) parallel groups controlled (with d vs. 41.4 mmol/d (higher dose); no
neuropathy and CAD) on elemental Mg; for 30 d change in FBG,
diet and/or OHA HgbA1C, BMI
Mg Eibl NL et al Double-blind; 2 40 Type 2 with Magnesium citrate; 30 mmol/ Placebo pill No change in HgbA1C, ⫺ 3 Exanthem (1),
Vanadium Cohen N et al Non-randomized; 6 Type 2; diet and/or OHA Vanadyl sulfate hydrate; Placebo capsule Decrease FBG, HgbA1C, ⫹⫹ N/A 5/6 transient
(1995) Single-blind; 100mg/day (Spectrum hepatic glucose gastrointestinal
Crossover Chemical, CA); for 3 wks production; increase discomfort; no
insulin-mediated effect on liver/
glucose uptake, kidney
insulin sensitivity; function
trend decrease
fructosamine; no
change PPG and C-
peptide
Vanadium Halberstam M et Non-randomized; 7 Type 2 Vanadyl sulfate hydrate; Placebo capsule Decrease FBG, HgbA1C, ⫹⫹ N/A 7/7 transient
al (1996) Single-blind; 100mg/day (Spectrum hepatic glucose gastrointestinal
Crossover Chemical, CA); for 3 wks output; increase discomfort no
insulin sensitivity; no effect liver/
change in insulin kidney function
Yeh and Associates
1283
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Vanadium Boden G et al Non-randomized; 8 Type 2; OHA and/or Vanadyl sulfate; 100mg/d; for Placebo capsule Decrease FBG, decrease ⫹⫹ N/A 4/8 diarrhea; 1/8
(1996) Single-blind; insulin 4 wks hepatic glucose nausea; 1/8
1284
Crossover output during clamp flatulence
Vit E Reaven PD et al Double-blind; 2 21 Type 2 men; on diet Vitamin E; 1600 IU/d dl- Placebo pill No change in FBG, PPG, ⫺ 4 No side effects
(1995) parallel groups and/or OHA alpha-tocopherol postprandial insulin,
(Hoffman-LaRoche); for 10 glycated Hgb,
wks glycated albumin,
glycated total plasma
proteins, fructos-
amine; decrease
susceptibility of LDL
to oxidation
Vit E Paolisso G et al Double-blind; 15 Type 2; well controlled Vitamin E; 900 mg/d dl- Sodium citrate Decrease HgbA1C, FPG, ⫹⫹ 3 No side effects
(1993) Crossover on diet and OHA alpha-tocopheryl acetate placebo PPG; no change in
(“Ephynal,” Roche, Italy); insulin, hepatic
for 4 mos glucose output,
Review of herbs/vitamins in diabetes
glucose oxidation;
increase total body
glucose disposal and
non-oxidative glucose
metabolism
Vit E Gomez-Perez FJ et Double-blind; 53 DM (39 Type 2, 14 Type Vitamin E; 1200 mg/d (Searle Placebo capsule No change in FBG, ⫺ 3 Not reported
al (1996) Crossover 1); poorly controlled on de Mexico SA de CV): for 2 fructosamine,
diet, OHA and/or insulin mos HgbA1C
Vit E Paolisso G et al Double-blind; 25 Type 2; well controlled Vitamin E; 900 mg/d d-alpha- Placebo pill Decrease FPG, HgbA1C, ⫹⫹ 3 No side effects;
(1993) Crossover on diet and OHA tocopherol (“Ephynal,” PPG; no change in no effect on
Roche, Italy); for 3 mos insulin liver/renal
function tests
Vit E Ceriello A et al Single-blind; 3 30 “insulin-requiring DM”; Vitamin E; 1200mg/d vs. 600 Placebo Decrease Hgb A1C and ⫹⫹ 1 Not reported
(1991) parallel groups on diet and insulin mg/d (unspecified glycosylated protein
preparation); for 2 mos (dose related); no
change in FPG or
mean daily glucose
Vit E Jain SK et al Non-randomized; 35 Type 1 Vitamin E; 100 IU/d; for 3 Placebo capsule Decrease glycated Hgb; ⫹ N/A Not reported
(1996) Double-blind; 2 mos no change FPG,
parallel groups insulin requirement
*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.
applicable.
RESULTS
trolled trials.
Coccinia indica
glycemic control
Single herbs/plant derivatives for
quired to categorize the trial as positive.
Coccinia indica is not well understood, but (n ⫽ 36 and n ⫽ 24); both reported de- evidence for allium species in glycemic
the herb appears to have insulin-mimetic creases in fasting blood glucose and control. (Level I, C)
properties (61-63). HbA1c (68,69). Only one case of insomnia
The one RCT of this herb (n ⫽ 32), was reported in these trials. Three other Ocimum sanctum
conducted in India, reported significant short-term metabolic trials in healthy vol- Ocimum sanctum (holy basil) is another
changes in glycemic control following 6 unteers also found decreases in postpran- commonly used herb in Ayurveda (relat-
weeks’ use of powder from locally ob- dial glucose (66,70,71). All but one of the ed species include Ocimum album and
tained crushed dried leaves in poorly con- clinical trials we examined were from the Ocimum basilicum). Studies in animal
trolled or otherwise untreated patients same investigator group. The available ev- models suggest hypoglycemic effects
with type 2 diabetes (64). Another three- idence for American ginseng in diabetes (77), although the mechanism of action
arm controlled clinical trial (n ⫽ 70) com- suggests a possible hypoglycemic effect; remains unknown. Postulated effects in-
pared 12 weeks’ use of dried herb pellets however, the trials are small and longer- clude enhanced -cell function and insu-
made from fresh leaves with no treatment term studies are needed. (Level I, A) lin secretion. The one available controlled
and oral hypoglycemic agents (chloprop- clinical trial of Ocimum sanctum (n ⫽ 40)
preparations of fenugreek before oral decrease in postprandial glucose and in- tes (n ⫽ 60) using a commercially
GTT. In these series of trials, whole raw sulin requirements, but no change in fast- available preparation (“Legalon” 600 mg/
seeds, extracted seed powder, gum isolate ing glucose when compared with the day; IBI Lorenzini, Milan, Italy) for 12
of seeds, and cooked whole seeds seemed control commercial tea (60). No effect months, with significant improvements
to decrease postprandial glucose levels, was seen in C-peptide levels, thereby sup- in glycemic control when compared with
whereas degummed seeds and cooked porting a non–insulin-mediated effect. no treatment (92). No adverse effects
leaves did not (79). Other open-label pro- No adverse effects were reported. Clearly, were reported. Further information and
spective cohort studies have followed pa- more information is needed before the ef- higher quality clinical trials are needed to
tients on fenugreek for up to 6 months ficacy of Ficus carica can be properly as- further investigate milk thistle in glycemic
with reported benefits in glycemic control sessed. (Level III, C) control. (Level III, C)
(79,81– 84). No adverse effects were re-
ported in these trials. There is some pre- Opuntia streptacantha Gymnema sylvestre
liminary evidence for the efficacy of Opuntia streptacantha (nopal) or the Gymnema sylvestre is another commonly
fenugreek that suggests further studies prickly pear cactus can be found in arid used herb in Ayurveda. The plant is a
nisms include increased insulin secretion, Multiple herb combinations for reported with this formulation. The avail-
tissue glucose uptake, liver muscle glyco- glycemic control able studies suggest that some TCM for-
gen synthesis, glucose oxidation, and de- Table 2 presents the controlled clinical mulations, but not others, may have
creased hepatic gluconeogenesis. Studies trials of multiple herb combinations for beneficial effects. However, the data are
in alloxan-induced diabetic rabbits have glycemic control in patients with diabetes. certainly limited and no formula has been
suggested hypoglycemic effects (98). studied in more than one trial. (Level I, C)
Two controlled short-term metabolic Combination formulas in TCM
trials in patients with type 2 diabetes (n ⫽ TCM encompasses a system of healing Combination formulas in Native
18 and n ⫽ 9) have reported acute effects that has origins over 2,000 years old. It American medicine
on blood glucose with Momordica charan- emphasizes the importance of a balanced Native American medicine refers to the
tia fruit juice, as well as subcutaneous and harmonious flow of “qi,” or “life healing practices from the people indige-
vegetable insulin extract (95,99). Two force,” and employs diverse modalities nous to North America; the approach
other small, uncontrolled open-label tri- such as acupuncture, massage, qigong, combines awareness of mind, body, and
and an individualized approach to herbal spirit and ritualistic observances with
als also reported positive effects on glyce-
been studied in patients with diabetes, excessive thirst, and frequent urination To our knowledge, this is the only report
three from Ayurveda (D-400, MA-471, (143). These studies all reported no ad- of vitamin C for glucose control.) The
and Ayush-82) (33,119 –121) and three verse effects. A recent meta-analysis by available data for magnesium are mixed,
from Siddha (Chendooram, Sandan- Althuis et al. (144) that included 15 RCTs and thus the evidence for efficacy in dia-
apodi, and Kadal Azhinjil) (122–125). (only 4 included diabetic individuals) re- betes is inconclusive. (Level I, C)
None have been examined in RCTs— ported that chromium had no effect on
only open-label prospective cohort stud- glucose or insulin concentrations in non-
ies or case reports. diabetic subjects; however, the data Vitamin E
among patients with diabetes were incon- Diabetes produces a state of increased free
Vitamins/trace elements/dietary clusive. Althuis et al. also suggested that radical activity. The purported effects of
supplements for glycemic control more trials should be performed in North vitamin E on glucose control relate to the
Table 3 presents the controlled clinical America, as the generalizabiltiy of trials vitamin’s potent lipophilic antioxidant ac-
trials of vitamin/mineral supplements for conducted in China is unknown given re- tivity, with possible influences on protein
glycemic control in patients with diabe- gional differences in diet and nutritional glycation, lipid oxidation, and insulin
Vanadium trial showed no changes in fasting blood mostly for supportive evidence from
Vanadium has been described as either a glucose (153). Another noncontrolled RCTs with methodological flaws or un-
nonessential nutrient or a nutrient that is trial offers supportive evidence for a controlled studies, or conflicting evidence
required only in minute quantities, as no change in insulin sensitivity (152). The with weight supporting the recommenda-
physiological role of the trace element has available data are limited and suggest that tion (online appendix B). Those supple-
yet to be found (35,149). Human defi- further elucidation of ␣-lipoic acids ac- ments that earned an A rating include
ciency has not been documented. There tions is needed. (Level II-3, C) Coccinia indica, American Ginseng, and L-
are no accurate assays in clinical settings, carnitine, with supportive evidence from
and there is no recommended daily allow- DISCUSSION — A total of 108 hu- at least one adequate RCT. However, ac-
ance. Vanadium exists in several valence man trials of herbs and vitamin/mineral cording to the criteria described by
forms, with vanadyl (⫹5) sulfate and so- supplements for glycemic control were Weiger et al. (56), no herb or supplement
dium metavanadate (⫹4) being the most obtained. Most trials examined supple- has sufficient evidence to actively recom-
common supplement forms. Its mecha- ments as an adjunct to conventional treat- mend or discourage its use among pa-
nism of action in glycemic control is ment with diet and/or medication. Of the tients with diabetes. That is, evidence
(e.g., surgeries or anesthesia) and in the dardize supplements, there is a general nisms of action so that applicability to
event of an adverse effect. lack of consistency across the market. type 1 or type 2 diabetes can be clarified.
Although the trials contained in this With vitamin and mineral supplements,
review reported very few adverse effects, these issues are less relevant. CONCLUSIONS — As interest in the
other sources mentioned potential or In addition, the development of potential benefit of herbs and supple-
theoretical effects for six supplements. proper supplement regulation and safety ments for diabetes grows, it will become
Theoretical cross-allergenicity was men- codes has been slow. Currently, all dietary increasingly important to monitor the
tioned with silymarin as a member of the supplements (including herbal products) progress of the clinical literature and to
aster family (daisy) and Trigonella as a are regulated under the Dietary Supple- communicate these findings to patients.
member of the leguminosae family (pea- ment Health and Education Act of 1994 Based on this review, there is insufficient
nuts), although no actual cases have been (DSHEA), which specifically differenti- evidence to actively recommend or dis-
reported. The most important potential ates supplements from drugs. Conse- courage use of any particular supplement,
drug-herb interaction was that of garlic or quently, DSHEA does not require the although most appeared to be generally
Trigonella with warfarin, as both herbs extensive premarket approval that the safe. Preliminary evidence of several
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