Clinical Review Complementary and alternative medicine for the treatment of type 2 diabetes Richard Nahas MD CCFP Matthew Moher Abstract
the most prevalent and fastest grow-ing diseases in Canada, responsible
OBJECTIVE To review clinical evidence supporting complementary and
for expenditures of 9 billion dollars per
alternative medicine interventions for improving glycemic control in type 2 diabetes mellitus.
year.1 Family physicians play a central role in the management of diabetes. Although
QUALITY OF EVIDENCE MEDLINE and EMBASE were searched from January
1966 to August 2008 using the term type 2 diabetes in combination with
each of the following terms for specific therapies selected by the authors:
they do not necessarily provide real-world
cinnamon, fenugreek, gymnema, green tea, fibre, momordica, chromium, and
benefits. In the recent ACCORD (Action to
vanadium. Only human clinical trials were selected for review.
Control Cardiovascular Risk in Diabetes)2
MAIN MESSAGE Chromium reduced glycosylated hemoglobin (HbA ) and
fasting blood glucose (FBG) levels in a large meta-analysis. Gymnema sylvestre
Vascular Disease: Preterax and Diamicron
reduced HbA levels in 2 smal open-label trials. Cinnamon improved FBG but its
MR Controlled Evaluation)3 trials, intensive
effects on HbA are unknown. Bitter melon had no effect in 2 smal trials. Fibre
glycemic control had minimal effect on clin-
had no consistent effect on HbA or FBG in 12 smal trials. Green tea reduced
ical cardiovascular outcomes. In fact, in a
FBG levels in 1 of 3 smal trials. Fenugreek reduced FBG in 1 of 3 smal trials. Va-
recent meta-analysis, combination therapy
nadium reduced FBG in smal , uncontrol ed trials. There were no trials evaluating
microvascular or macrovascular complications or other clinical end points.
the risk of a composite end point of car-
CONCLUSION Chromium, and possibly gymnema, appears to improve gly-
diovascular events and mortality (relative
cemic control. Fibre, green tea, and fenugreek have other benefits but there
risk 1.43, 95% confidence interval [CI] 1.10
is little evidence that they substantially improve glycemic control. Further
to 1.85).4 The use of thiazolidinediones has
research on bitter melon and cinnamon is warranted. There is no comple-
recently been called into question because
mentary and alternative medicine research addressing microvascular or
they increase cardiovascular risk and frac-
using complementary and alternative medi-
OBJECTIF Faire le point sur les données cliniques en faveur d’interventions
cine (CAM) therapies,6 often without con-
de médecine complémentaire et alternative pour améliorer le contrôle de la
sulting or even informing their FPs. It is
glycémie dans le diabète de type 2. QUALITÉ DES PREUVES On a consulté MEDLINE et EMBASE entre janvier 1966
their CAM use and provide evidence-based
et août 2008 à l’aide du terme type 2 diabetes en combinaison avec chacun des
information about the safety and efficacy of
termes suivants pour des traitements spécifiques, choisis par les auteurs : cinna-mon, fenugreek, gymnema, green tea, fibre, momordica, chromium et vanadium.
Here we provide a brief review of the evi-
Seuls les essais cliniques humains ont été retenus pour cette étude. PRINCIPAL MESSAGE Le chrome a réduit l’hémoglobine glycosylée (HbA )
therapies commonly used to treat type 2 DM.
et la glycémie à jeun (GÀJ) dans une grande méta-analyse. Le gymnema sylvestre a réduit les niveaux d’ HbA dans 2 petits essais sans insu. La can-
Quality of evidence
nelle a amélioré la GÀJ, mais on ignore ses effets sur l’ HbA . La margose n’a
eu aucun effet dans 2 petits essais. Les fibres ont eu des effets variables sur le
HbA ou sur la GÀJ dans 12 petits essais. Le thé vert a abaissé la GÀJ dans 1
essai sur 3. Le fenugrec a diminué la GÀJ dans un essai sur 3. Le vanadium a
key words were type 2 diabetes in combi-
réduit la GÀJ dans des petits essais non contrôlés. Aucun essai n’a évalué les
nation with each of cinnamon, fenugreek,
complications micro ou macro-vasculaires, ou d’autres issues cliniques. gymnema, green tea, fibre, momordica, chro-CONCLUSION Le chrome et possiblement le gymnema sylvestre semblent mium, and vanadium. These interventions
améliorer le contrôle de la glycémie. Les fibres, le thé vert et le fenugrec
ont d’autres effets bénéfiques, mais il y a peu de données indiquant qu’ils améliorent le contrôle de la glycémie. La margose et la cannelle mériteraient
This article has been peer reviewed.
d’autres études. Il n’existe aucune recherche en médecine complémentaire et
Cet article a fait l’objet d’une révision par des pairs.
alternative sur les issues cliniques micro ou macro-vasculaires. Vol 55: JUNE • JUIN 2009Canadian Family Physician • Le Médecin de famille canadien 591 Clinical ReviewComplementary and alternative medicine
literature reviews and clinical experience. Results were
is contact dermatitis from volatile oils. Safety in preg-
screened by one author to include clinical trials, system-
atic reviews, and meta-analyses. Only human clinical
Overall, there is moderate evidence that cinnamon
lowers blood glucose levels. Its effect on HbA appears
negligible, but long-term studies are required to prop-
Relevant findings for each search term are briefly sum-marized in Table 1 and are detailed as follows:
Chromium. Chromium is an essential trace element with many sites of action, including carbohydrate and
Cinnamon. True cinnamon (Cinnamomum verum) is
lipid metabolism. Trivalent chromium is a constituent
a small evergreen tree, the bark of which is a common
of a complex known as the “glucose tolerance factor,”15
culinary spice. Most cinnamon sold in the United States
and chromium deficiency causes reversible insulin resis-
and Canada is actually derived from C aromaticum or
C cassia, sometimes called “Chinese cinnamon” to dis-
A meta-analysis identified 41 trials (N = 1198) that
tinguish it from C verum. Cinnamon has been used for
evaluated the effects of various chromium formula-
thousands of years to treat diabetes and other condi-
tions at doses of 200 to 1000 µg daily for 2 to 26 weeks.
tions. The aqueous extract appears to activate the insu-
Of these, 14 trials (n = 431) evaluated patients with
lin receptor by multiple mechanisms, and also increases
type 2 DM and baseline HbA levels of 7.0% to 10.2%.
Chromium picolinate and brewer’s yeast at doses of 200
A recent meta-analysis identified 5 trials (N = 282) that
to 1000 µg for 6 to 26 weeks reduced HbA levels by an
evaluated C cassia at 1 to 6 g daily for 40 days to 4
average of 0.6% (95% CI -0.9% to -0.2%) and FBG levels
months.11 One trial was not randomized, while another
by an average of 1 mmol/L (95% CI -1.4 to -0.5).19 These
trial investigated adolescents with type 1 diabetes. The
findings are limited by the fact that more than half the
other 3 randomized controlled trials (RCTs) involved
studies included were of poor quality and used different
196 patients. In one, 60 patients with poorly controlled
formulations and doses of chromium in populations that
diabetes were given 1, 3, or 6 g of C cassia for 40 days.
might have had very different amounts of chromium in
Fasting blood glucose (FBG) levels decreased by 18%
their diet. No significant adverse effects were reported in
to 29%, but chromium-reduced glycosylated hemoglo-
bin (HbA ) levels were not investigated.12 In a second
The meta-analysis included 2 RCTs that evaluated
trial, 79 well-controlled diabetes patients received 3 g of
combination therapy using 600 µg chromium pico-
C cassia daily for 4 months. More moderate reductions
linate and 2 mg biotin. Biotin is a B vitamin that has
in FBG levels (average 10.3% vs 3.4% in placebo group,
enhanced chromium absorption in animal studies.
P = .046) were noted, but HbA levels were unchanged.13
One 3-month trial in 447 patients with diabetes (mean
In the third trial, 43 patients with diabetes with an aver-
baseline HbA level 8.6%) noted an HbA level reduc-
age HbA measurement of 7.1% were treated with 1 g
tion of 0.54% (P = .03) overall, and an impressive 1.76%
daily for 3 months. No change was reported in FBG or
reduction among patients with baseline HbA levels
above 10% (P = .0001).20 In the second trial, 36 patients
No significant adverse effects were reported in the
with diabetes were treated for 1 month; no reduction in
reviewed trials. The only reported risk of cinnamon use
Table 1. Summary of evidence supporting complementary and alternative medicine therapies for type 2 diabetes mellitus INteRveNtIoN BoDy oF evIDeNCe
HbA and FBG level reduction in meta-analysis
FBG level reduction in uncontrolled trials
HbA level reduction (non-significant) in 1 of 3 trials FBG level reduction in 6 of 12 trials
FBG level reduction in 1 of 3 trials Other benefits
No benefit to HbA or FBG levels in 2 small trials
FBG level reduction in 1 of 3 trials Other benefits
HbA —glycosylated hemoglobin A , FBG—fasting blood glucose. 592 Canadian Family Physician • Le Médecin de famille canadienVol 55: JUNE • JUIN 2009 Complementary and alternative medicineClinical Review
There is strong evidence that 200 to 1000 µg of chro-
the freshly collected leaves. The numerous health ben-
mium picolinate daily improves glycemic control. Based
efits of tea consumption are attributed to polyphe-
on its safety and potential cost-effectiveness, a definitive
nol catechins, particularly epigallocatechin gallate.45,46
clinical trial is urgently needed. Biotin might enhance its
These compounds have improved insulin sensitivity and
effects, but this combination requires further study.
reduced β-cell damage in animal and in vitro studies.47-53
Although caffeine initially impairs glucose metabolism,
Vanadium. Vanadium is a poorly understood trace
long-term exposure stimulates lipolysis, increases basal
element that is ubiquitous in nature and believed to
energy expenditure, and mobilizes muscle glycogen.54,55
have many functions in human physiology. In vitro and
Prospective and retrospective population studies sug-
animal studies have demonstrated its insulinomimetic
gest that green tea consumption reduces the risk of type
effects mediated by inhibition of phosphotyrosine phos-
2 DM by up to 48%.56,57 Surprisingly, only 1 small RCT
phatase enzymes that affect the insulin receptor.22-24
(N = 49) has evaluated green tea in the context of dia-
A recent meta-analysis identified 5 uncontrolled trials
betes. In this study, patients with baseline HbA levels
(N = 48) in which 50 to 300 mg of vanadium was admin-
of 6.5% to 9.1% were randomized to receive either an
istered for 3 to 6 weeks.25 Vanadyl sulfate was used in
extract containing green tea catechins and black tea
4 trials and sodium metavanadate was used in 1 trial.
theaflavins or placebo for 3 months. No improvements
All 5 trials reported reductions in FBG levels, but these
in HbA levels were seen and FBG values were not
were of short duration; none of the trials included con-
measured.58 Side effects included a generalized rash in 1
trols. Commonly reported side effects included gastroin-
testinal upset, bloating, and nausea.
Three open-label trials (N = 141) of 1 to 2 months’
There is insufficient evidence to support the use of
duration reported no changes in HbA values.59-61
vanadium in the treatment of type 2 DM.
Investigators in one trial administered 1.5 L of oolong
(partly oxidized) tea to 20 patients for 4 weeks and
Fibre. Dietary fibre is recognized as an important part
reported a 30% decrease in FBG levels (P < .001).44
of a healthy diet. Soluble and insoluble fibre have posi-
There is little evidence to support the use of green tea
tive effects on cardiovascular risk factors,26 intestinal
for glycemic control. Epidemiologic data suggest large
disorders,27 and certain cancers.28-30 Cohort studies sug-
potential benefits, but further research is warranted.
gest that consumption of cereal fibre and whole grains is
Green tea consumption should still be recommended for
inversely related to type 2 DM incidence.31
its other potential health benefits.
We identified 12 small RCTs (N = 345) that evaluated
the effect of fibre in diabetes patients.32-43 Many differ-
Bitter melon. Bitter melon (Momordica charantia) is
ent kinds of fibre were used, including wheat, guar, beet,
a tropical vine that produces fruit that is used to treat
soy, corn, agar, glucomannan, psyllium, and mixtures.
diabetes in many traditional cultures, including Indian
Daily doses of 2 to 50 g were administered for 3 to 20
Ayurvedic medicine. Several of its active ingredients,
weeks. In 3 trials of 12 to 20 weeks’ duration, only 1
including charantin, vicine, and polypeptide-p,62-64 are
found an improvement in HbA levels: in this trial of 76
believed to stimulate insulin secretion and alter hepatic
patients with well-controlled diabetes, a non-significant
decrease from 6.6% to 6.1% was seen in those who con-
Two RCTs have evaluated the effects of bitter melon
sumed agar containing 4.5 g fibre daily for 12 weeks. Six
in patients with type 2 DM. In one RCT, 40 patients with
of the 12 RCTs reported reductions in FBG; the other 6
baseline HbA values of 7% to 9% were given either
RCTs reported no change in this outcome. Most of the
3 g of fruit and seed extract or placebo. After 3 months,
studies also reported improvements in other risk factors,
there was no change in HbA or FBG values.68 The other
particularly those related to cholesterol levels. Some
trial, in which 51 patients consumed either 6 g of fruit
trials reported gastrointestinal side effects, including
and seed extract or placebo for 1 month, also reported
bloating, diarrhea, and abdominal pain.44
no effect on HbA or FBG values.69 No side effects were
There is little evidence that dietary fibre improves gly-
cemic control. Existing trials are limited by the hetero-
There is no evidence to support the use of bit-
geneity of fibre formulations and the variation in doses
ter melon. It should be noted that stimulating insulin
and duration of treatment. Evidence of a short-term
release is probably less desirable than improving insu-
hypoglycemic effect in diabetes patients is conflicting.
lin sensitivity. Bitter melon’s widespread traditional use
Nonetheless, fibre can be recommended based on its
merits further study, particularly in patients originating
salutary effect on other cardiovascular risk factors.
from cultures with a long history of traditional use. Green tea. Green and black tea both originate from the
Fenugreek. Fenugreek (Trigonella foenum-graecum)
leaves of the Camellia sinensis plant. Green tea is heated
has been cultivated and used medicinally and ceremoni-
to inactivate the enzymes that would otherwise oxidize
ally for thousands of years in Asian and Mediterranean
Vol 55: JUNE • JUIN 2009Canadian Family Physician • Le Médecin de famille canadien 593 Clinical ReviewComplementary and alternative medicine
cultures. Its leaves and seeds are used to treat diabetes
EDITOR’S KEY POINTS
in Ayurvedic and other traditional medical systems. The
• Chromium (200 to 1000 µg per day) is the only
most studied active ingredient is 4-hydroxyisoleucine,
complementary and alternative medicine interven-
which increases pancreatic insulin secretion and inhibits
tion with level 1 evidence to support its use in dia-
sucrose α-D-glucosidase and α-amylase.70-72 Additionally,
betes management, but a large-scale clinical trial is
fenugreek seeds are used to lower cholesterol, as sapo-
genins in the seeds increase biliary secretion73-80; they
• Small studies indicate that Gymnema sylvestre
improves HbA levels. Larger studies are required to
Three small short-term RCTs (N = 50) have evaluated
fenugreek in patients with type 2 DM. In one trial, 25
• Cinnamon probably lowers blood glucose levels, but
patients consumed 1 g of seed extract or placebo for
its effects on HbA levels are unknown.
2 months with no change in FBG levels.81 In a small
• Bitter melon has a long history of traditional use,
crossover study, 10 patients added 25 g of defatted seed
but preliminary evidence suggests its benefits might
powder to 1 meal or ate the meal without the powder
for 15 days. Several measures of glucose metabolism
• Vanadium is poorly understood, has potential
were all unchanged.82 A third trial, which used a higher
adverse side effects, and should probably be avoided.
dose (100 g) of defatted seed powder in 15 patients for
• Green tea, fenugreek, and fibre can be recom-
10 days, did report improvements in FBG values.83 None
mended on account of their other health benefits,
of the trials investigated HbA levels. No adverse effects
but evidence that they improve glycemic control is
There is very limited evidence to support the use of
fenugreek in diabetes management. High doses of seed
POINTS DE REPèRE DU RÉDACTEUR
powder might be effective but require further study and
• La seule substance en médecine complémentaire
are likely impractical for most patients. Its widespread
et alternative dont l’usage dans le traitement du
traditional use and its reported lipid-lowering benefits
diabète s’appuie sur des preuves de niveau 1 est
le chrome (200 à 1000 μg/d), mais il faudra un essai clinique à grande échelle pour confirmer ces
Gymnema.Gymnema sylvestre is also known as gur-mar (sugar destroyer) in Hindi. The leaves of this plant
• Certaines petites études indiquent que le gymnema
are used in Ayurvedic medicine to treat diabetes, choles-
sylvestre améliore les niveaux de HbA . Ces résultats
terol, and obesity.84 Gymnemic acid, a mixture of many
prometteurs devront être confirmés par de plus
different saponins, is believed to be the active fraction,
although a clear mechanism of action is yet to be been
• La cannelle abaisse probablement le glucose sanguin,
Two small open-label trials have yielded promising
• La margose est d’usage traditionnel depuis long-
results. In the first trial, 22 patients with type 2 DM were
temps, mais des données préliminaires suggèrent
given either 200 mg of an ethanolic extract daily or
que ses avantages pourraient être limités.
their usual treatment for 18 to 20 months. Significant
• Les effets du vanadium sont mal connus; il pourrait
improvements in FBG and HbA levels (P < .001 for
avoir des effets indésirables et on devrait vraisem-
both) were noted in the test group.86 The other trial was
uncontrolled, but reported that 3 months of treatment
• Le thé vert, le fenugrec et les fibres peuvent
with 800 mg daily of a similar extract reduced FBG lev-
être recommandés à cause de leurs autres effets
els by 11% and HbA levels by 0.6% in a mixed popula-
bénéfiques sur la santé, mais les preuves qu’ils
tion of 65 patients with type 1 and type 2 diabetes.87 No
améliorent le contrôle de la glycémie sont limitées
adverse effects were reported in either trial.
Preliminary evidence of any benefit is probably insuf-
ficient to support the widespread use of G sylvestre for diabetes management at this time. The significant
involve HbA measurements and should be of at least
improvements in HbA levels definitely warrant further
4 months’ duration. Most of these trials were of insuf-
study as well as judicious use in selected patients.
ficient duration to evaluate this outcome. None of the research examined has addressed the potential effect
of CAM interventions on cardiovascular outcomes. This
Changes in HbA values are most often used to evalu-
is important because better glycemic control might not
ate hypoglycemic effects. It is important to consider that
always lead to real-world clinical benefits. It is also
the life span of a red blood cell is 120 days. Therefore,
important because some interventions can improve
studies investigating diabetes management should
594 Canadian Family Physician • Le Médecin de famille canadienVol 55: JUNE • JUIN 2009 Complementary and alternative medicineClinical Review
Overall, there is a paucity of research evaluating
overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev 2008;24(1):41-51.
CAM therapies that are commonly used to treat type 2
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DM. This should be a high priority for CAM researchers
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22. O’Connell BS. Selected vitamins and minerals in the management of diabe-
Dr Nahas is a Lecturer in the Department of Family Medicine at the University
tes. Diabetes Spectrum 2001;14(3):133-48. Available from: http://spectrum.
of Ottawa and Medical Director of the Seekers Centre for Integrative Medicine
diabetesjournals.org/cgi/reprint/14/3/133.pdf. Accessed 2009 Apr 17.
in Ottawa, Ont. Mr Moher is a fourth-year medical student at the University of
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sulfate-stimulated glycogen synthesis is associated with activation of
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Developing World Bioethics ISSN 1471-8731 (print); 1471-8847 (online) FROM PMTCT TO A MORE COMPREHENSIVE AIDS RESPONSE FOR WOMEN: A MUCH-NEEDED SHIFT CYNTHIA EYAKUZE, DEBRA A. JONES, ANN M. STARRS AND NAOMI SORKIN Keywords PMTCT, ABSTRACT Half of the 33.2 million people living with HIV today are women. Yet, responses to the epidemic are not adequately meeting the needs of wom
Supplemento di Segnalazioni Bibliografiche Gennaio 2000 Are a i nform ativa "L'ultimo sballo" Londra rappresenta da sempre una città che fa tendenza nell’uso di nuove sostanze Negli ultimi tempi sembra che stia prendendo sempre più forza l’abitudine di assumere, insieme a droghe eccitanti come l’ecstasy o la cocaina, pillole di Viagra. L’effetto prov