Pro4u.co.il

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- Résumé
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 2009 Canadian Family Physician • Le Médecin de famille canadien 591
Clinical Review Complementary 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- Main findings
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.
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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 2009 Canadian Family Physician • Le Médecin de famille canadien 593
Clinical Review Complementary 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 Conclusion
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 canadien Vol 55: JUNE • JUIN 2009
Complementary and alternative medicine Clinical 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 21. Geohas J, Daly A, Juturu V, Finch M, Komorowski JR. Chromium picolinate DM. This should be a high priority for CAM researchers and biotin combination reduces atherogenic index of plasma in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Am J Med Sci 2007;333(3):145-53.
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 23. Verma S, Cam MC, McNeill JH. Nutritional factors that can favorably influ- ence the glucose/insulin system: vanadium. J Am Coll Nutr 1998;17(1):11-8.
Contributors
24. Pandey SK, Anand-Srivastava MB, Srivastava AK. Vanadyl Dr Nahas and Mr Moher contributed to the literature review, selection and sulfate-stimulated glycogen synthesis is associated with activation of review of studies, and preparation of the manuscript for publication.
phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. Biochemistry 1998;37(19):7006-14.
Competing interests
25. Smith DM, Pickering RM, Lewith GT. A systematic review of vanadium oral supplements for glycaemic control in type 2 diabetes mellitus. QJM Correspondence
Dr R. Nahas, Medical Director, Seekers Centre for Integrative Medicine, 6 26. Galisteo M, Duarte J, Zarzuelo A. Effects of dietary fibers on disturbances Deakin St, Ottawa, ON K2E 1B3; e-mail [email protected] clustered in the metabolic syndrome. J Nutr Biochem 2008;19(2):71-84. Epub 2007 Jul 6.
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