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An evaluation of the product containing Peria Katak (Momordica charantia).

INTRODUCTION

Within the population of Malaysia, Momordica charantia is among the traditional vegetables or generally referred to as "ulam" and is locally known as Peria Katak. [1] It is commonly consumed for its effect on blood glucose levels. [1] M. charantia or bitter melon has been suggested to produce hypoglycemic effect via utilization of various forms and extracts of the plant. [2]

More than 20 brand of supplements containing M. charantia is listed and granted registration codes by the National Pharmaceutical Control Bureau. [3] Despite limitations on available published clinical trial on findings of efficacy and safety, the product is widely advertised for its hypoglycemic properties. This somehow indicates the extensive usage in our local community, which is possibly related to the increased prevalence of diabetes cases in Malaysia. [4]

This brief review is conducted to evaluate the efficacy and safety of M. charantia based on relevant studies and reviews.

METHODOLOGY

An electronic search for studies on the effectiveness and safety of M. charantia was carried out from resources of MEDLINE, Cochrane Library, trial, and reviews. The relevant studies and reviews are summarized in Table 1, inclusive of trials conducted in human, with the evaluated preparation administered orally.

PHARMACOKINETIC

Limited data are available with regard to the pharmacokinetic properties of m. Charantia. The dried powder form of the fruit, orally administered in mice, produces a peak effect at 10 h with half-life of 7.6 Min. [5] Distribution site was found highest in kidney, lung, liver, stomach, and brain.

EFFICACY IN TRIALS

In a double-blind, randomized, placebo-controlled trial that looks at the glycemic effect by the capsule formulation of M. charantia, result was inconclusive as the power achieved was only 11% even though a difference in the hemoglobin A1c (HbA1c) value was shown in the treatment group receiving M. charantia. [6]

In a randomized, two-arm, parallel placebo-controlled trial on glycemic effect as well as the glycation status by the dried pulp preparation of M. charantia, findings provide preliminary evidence on the significant benefit of M. charantia in the form of dried fruit pulp in reducing levels of HbAlc up to 16 weeks. [7] In addition, decrement of total advanced glycation end products that relates to long-term complications in diabetic such as nephropathy and retinopathy implies its potential profit in preventing the associated microvascular complications.

Another randomized controlled trial assesses the potential of M. charantia as a hypoglycemic agent. [8] The administration of M. charantia at the dose used in this study as a dried whole fruit does not produce any significant effects in lowering blood sugar.

A multicenter, randomized, double-blind, active control trial by Fuangchan et al. evaluates the efficacy of bitter melon at three different dose ranges in comparison to conventional oral hypoglycemic agent--metformin in means of hypoglycemic effect. [9] Findings from the study showed that glycemic control was achievable by both metformin and bitter melon at a daily dose of 1000 mg/day and 2000 mg/day with reference to fructosamine concentrations, respectively. Nevertheless, the hypoglycemic effect of bitter melon is lesser in comparison to metformin. Study provides a base on the feasible dose of M. charantia in the form of dried powder that may be used for future studies.

A systematic review of randomized trials evaluates the effect M. charantia in type 2 diabetes patients administering oral preparations in a variety of forms and dosages. The preparations were taken alone, or concurrently with oral hypoglycemic agents, with or without insulin. [10] Having most studies not exhibiting statistically significant differences between M. charantia consumption and placebo or other medication, suggestion was made to perform more trials in providing standardization over issues and the quality control to make sound recommendations that may be placed in practice.

SAFETY

Monitoring done in studies reveals insignificant effect on tested laboratory findings including alanine aminotransferase, aspartate aminotransferase, [6,7,9,11] and serum creatinine [6,7,11] in patients administering M. charantia of specified doses in the particular studies. Caution is somehow to be exercised for use in those with existing liver impairment or actively consuming drugs that is known to induce hepatotoxicity. [5]

Report on mild side effect includes gastrointestinal [7,11] and central nervous system [9] related. Nonetheless, they are not regarded as conclusive as length of reported studies is limited from only weeks to months. It is, however, worth to note on the more seriously reported adverse event, hypoglycemic coma and convulsions in children. [12]

Precaution is as well advice in individuals with glucose-6-phosphate-dehydrogenase deficient due to the risk of favism following exposure to the seeds of M. charantia [12] and in expecting women due to risk of miscarriage. [13]

With the incomplete pharmacokinetic findings, administration by patients with existing renal, liver impairment places them at risk.

Interaction is another aspect to be discussed. A minimum drug interaction data are documented on M. charantia, with most of reviews mentioning the synergistic effect when taken together with hypoglycemic agents. [14-16] Hence, patients should be educated on the danger of extreme hypoglycemic level if they were taken together improperly, regardless of form of preparation. In addition, ingestion of multiple types of herbal, may it be part of daily meal or as dietary supplement without knowing their similar pharmacological actions, further places a patient at risk by potentiating the effect of one another.

Even though clinical findings are not conclusive on the hypoglycemic effect by bitter melon, results do somehow demonstrate the blood glucose lowering effect. Synergistic effect provides idea on the claimed role, but recommendation on the required dose adjustment to prevent risk of hypoglycemic is not presented. Therefore, health care professionals should always be conscious on the possibilities of intake with the prescribed hypoglycemic agents and be able to offer evidence-based explanation particularly on the safety matters on its ingestion.

A cross-sectional study by Ching et al. revealed 62.5% prevalence on complementary and alternative usage among type 2 diabetic patients in a local setting, with bitter gourd (M. charantia) being the mostly consumed herbal based alternative. [17] They described that part of the reason on such would be the belief that these complementary medicines potentially ameliorate the diabetes condition.

The safety factor following intake of herbal-based supplements may not be a major consideration since mostly may regard them as a common "ulam" included in daily meals. Method of consumption varies from the capsule preparation to dried fruit.

Up to date, even preparations used in clinical trials are not of standardized formulation, [10] indicating that a well-formulated preparation that is effective as a hypoglycemic agent, far more in terms of safety, has not been identified yet. Thus, the various forms of bitter melon consumed, when it is not recognized, pose risk in terms of unproven efficacy against the claimed effect since available trial does not provide definitive findings. Also, risk of toxicity should be concerned about, if the doses in use are beyond the therapeutic range, that presently remains unknown. Moreover, available trials do not directly evaluate the safety outcomes with regard to the administration of bitter melon. Safety measures were mostly additional outcome in the findings.

Apart from that, description on the adverse events is limited to length of study between 4 weeks to 3 months only. [10] Having patients consuming the herbal supplements over years, [17] result for longer terms should instead be considered. Safety aspects following long-term exposure are paramount importance since diabetic itself is a chronic condition that brings about the likelihood of prolonged intake.

It is noted that most trials are conducted within Asia vicinity, possibly due to the accessibility of the herbal diversity. Thus, wide consumption may be linked to the availability in the country. Having multiple risks, prolonged use without proper monitoring may compromise the overall management plan.

RECOMMENDATION AND CONCLUSION

In all of the reviewed clinical trials, dissimilar outcome measures were used such as fasting blood glucose levels, [6,9] HbA1c, [6,7] and fructosamine levels. [6,9] Furthermore, parts of the M. charantia in use also differ in all studies. This somehow renders difficulty in providing a collective assessment. As known, dietary intake and physical activities play a role in part of diabetes management that can affect glucose level. With no direct control, these confounding factors may impinge the outcome measure. Although supportive outcomes were noted in some of the studies, nevertheless, attention on the study design, duration of study, and sample size (which is mostly small) should be accounted in deriving conclusions.

Thus, further studies with larger sample, longer period, controlled environment with the use of standard preparation of the herb are needed to allow concrete conclusion to be made and placed in practice. Definite findings of dosage form and dosage in use to achieve hypoglycemic effect, safely, are also necessary. As for the meantime, findings generated from the studies only provide implication on the potential advantages that M. charantia offers in preventing and managing type 2 diabetes as well as microvascular complications instead of a certain conclusion.

Complete pharmacokinetic data in human are still unavailable. The reviewed studies recruited patients with normal kidney and liver function. Although insignificant changes were seen at the end of study periods, [7,9] intake of preparation is not advised in patients with existing impairment until further explored.

Patients should be encouraged to report the use of this preparation as monitoring is vital in view of the precaution warranted for the specific individuals and unknown herbal-drug or herbal-food interaction that could possibly interrupt the overall management plan.

It was found that ideation on the use of these complementary medicines within the local diabetes mellitus population comes from friends, family members, and media. [17] Multimedia may be utilized for sellers of these products to reach consumers. This is inclusive of the internet that provides information and as a tool that eases availability. [18]

In the local setting, healthcare providers in particular and the public are to be aware on the importance of any marketed product conforming to the guide as outlined by the Malaysia's Medicine Advertisement Board. [19] Advertisement requirement includes complete information of product to avoid ambiguity, advisory statement for continued consultation with physician to monitor blood glucose and hypoglycemic agent adjustment, owing to the risk of potentiated effect. Safety detail on the use of product should also be informed.

Advertiser holds social responsibility in avoiding misleading understanding by the public. Example of such deprivation includes the inclusion of testimonials without mentioning that the effect somehow varies between individuals and using "guaranteed" term that may delude public's estimation on the actual value of product.

Until hypoglycemic effect is made evident through more reliable findings, M. charantia or bitter melon preparations from the evidence-based view should not be encouraged. Nonetheless, with continuation of intake, the preparation being in any form should only be regarded as a supplement and not an alternate to the established therapy in place with continuous monitoring.

DOI: 10.4103/2045-080X.183035

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

For reprints contact: reprints@medknow.com

Financial support and sponsorship

This work was supported by Research Acculturation Grant Scheme: RAGS/1/2014/SKK07/UITM//7. The authors would like to express their gratitude to Ministry of Higher Education and Universiti Teknologi MARA (UiTM), Malaysia for financial support for this research.

Conflicts of interest

There are no conflicts of interest.

REFERENCES

[1.] Bachok MF, Yusof BN, Ismail A, Hamid AA. Effectiveness of traditional Malaysian vegetables (ulam) in modulating blood glucose levels. Asia Pac J Clin Nutr 2014; 23:369-76.

[2.] World Health Organization. WHO. Monographs on Selected Medicinal Plants. Vol. 4. Spain: WHO Library Cataloguing-in-Publication Data; 2009.

[3.] National Pharmaceutical Control Bureau. Quest 3 Product Search; 2015. Available from: http://www.quest3.bpfk. gov.my/. [Last accessed 2015 Oct 09].

[4.] Wan Nazaimoon WM, Md Isa SH, Wan Mohamad WB, Khir AS, Kamaruddin NA, Kamarul IM, et al. Prevalence of diabetes in Malaysia and usefulness of HbA1c as a diagnostic criterion. Diabet Med 2013; 30:825-8.

[5.] Micromedex Health Solutions. Micromedex Solutions; 2015. Available from: http://www.micromedex.com/. [Lasst accessed on 2015 Oct 09].

[6.] Dans AM, Villarruz MV, Jimeno CA, Javelosa MA, Chua J, Bautista R, et al. The effect of Momordica charantia capsule preparation on glycemic control in type 2 diabetes mellitus needs further studies. J Clin Epidemiol 2007; 60:554-9.

[7.] Trakoon-osot W, Sotanaphun U, Phanachet P, Porasuphatana S, Udomsubpayakul U, Komindr S. Pilot study: Hypoglycemic and antiglycation activities of bitter melon (Momordica charantia L.) in type 2 diabetic patients. J Pharm Res 2013; 6:859e864.

[8.] John AJ, Cherian R, Subhash HS, Cherian AM. Evaluation of the efficacy of bitter gourd (Momordica charantia) as an oral hypoglycemic agent--A randomized controlled clinical trial. Indian J Physiol Pharmacol 2003; 47:363-5.

[9.] Fuangchan A, Sonthisombat P, Seubnukarn T, Chanouan R, Chotchaisuwat P, Sirigulsatien V, et al. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol 2011; 134:422-8.

[10.] Ooi CP, Yassin Z, Hamid TA. Momordica charantia for type 2 diabetes mellitus. Cochrane Database Syst Rev 2012; 8:CD007845.

[11.] Tsai CH, Chen EC, Tsay HS, Huang CJ. Wild bitter gourd improves metabolic syndrome: A preliminary dietary supplementation trial. Nutr J 2012; 11:4.

[12.] Basch E, Gabardi S, Ulbricht C. Bitter melon (Momordica charantia): A review of efficacy and safety. Am J Health Syst Pharm 2003; 60:356-9.

[13.] Geil P, Shane-McWhorter L. Dietary supplements in the management of diabetes: Potential risks and benefits. J Am Diet Assoc 2008; 108 4 Suppl 1:S59-65.

[14.] Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355:134-8.

[15.] Prabhakar PK, Kumar A, Doble M. Combination therapy: A new strategy to manage diabetes and its complications. Phytomedicine 2014; 21:123-30.

[16.] Rehman SU, Choi MS, Choe K, Yoo HH. Interactions between herbs and antidiabetics: An overview of the mechanisms, evidence, importance, and management. Arch Pharm Res 2015; 38:1281-98.

[17.] Ching SM, Zakaria ZA, Paimin F, Jalalian M. Complementary alternative medicine use among patients with type 2 diabetes mellitus in the primary care setting: A cross-sectional study in Malaysia. BMC Complement Altern Med 2013; 13:148.

[18.] Covolo L, Capelli M, Ceretti E, Feretti D, Caimi L, Gelatti U. Nutritional supplements for diabetes sold on the internet: Business or health promotion? BMC Public Health 2013; 13:777.

[19.] Medicine Advertisements Board. Guideline on Advertising of Medicines and Medicinal Products to General Public. Malaysia: Medicine Advertisements Board; 2015.

Nur Irnawaty Zainol (1), Sundara Rajan Mahalingam (3), Sandy Gim Ming Ong (4), Kamaruddin Arshad (2,3), Long Chiau Ming (1,3)

(1) Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, (3) Vector-borne Diseases Research Group (VERDI), Pharmaceutical and Life Sciences CoRe, Universiti Teknologi MARA, Shah Alam, Selangor, (2) Department of Environmental Health, Faculty of Health Sciences, Universiti Teknologi MARA, Bertam, (4) School of Pharmaceutical Sciences, University of Science Malaysia, Penang, Malaysia

Address for correspondence:

Nur Irnawaty Zainol, Level 11, FF1 Building, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor, Malaysia.

E-mail: nrirna@selayanghospital.gov.my
Table 1: Studies on Momordica charantia

Study           Design           Number of   Intervention
                                 patients

Dans et al.,    A                 40 (20     Each patient
2007            randomized,      patients    instructed to
                double-blind,      each      administer 2 capsules
                placebo-          group)     of either treatment
                controlled                   (M. charantia content)
                trial                        or placebo capsules,
                                             3 times daily (dose
                                             not specified)

Trakoon-osot    A two-arm,          38       Participants were
et al., 2013    parallel,                    randomized to take
                randomized,                  either 6 g/day of
                placebo-                     M. charantia dried
                controlled                   fruit pulp in 3 divided
                trial                        doses 30 min before
                                             meals or placebo

John et al.,    Randomized,         50       2 tablet, 3 times daily
2003            controlled                   (1 tablet contains
                trial                        1 g of dried fruit
                                             M. charantia)

Fuangchan       A                   143      Randomly assign
et al., 2011    multicenter,                 patients to receive
                randomized,                  either 500 mg/day,
                double-blind,                1000 mg/day,
                active-control               2000 mg/day of bitter
                trial                        melon or
                                             1000 mg/day
                                             of metformin

Ooi et al.,     Systematic          --       M. charantia orally
2012            review                       administered in a
                                             variety of forms
                                             and dosages.
                                             Taken alone or
                                             concurrently with oral
                                             hypoglycemic agents
                                             with or without
                                             insulin

Study           Existing       Length of
                medication     follow-up

Dans et al.,    Existing        3 months
2007            medications
                continued
                without dose
                modification

Trakoon-osot    Existing        16 weeks
et al., 2013    medications
                continued
                without dose
                modification

John et al.,    Existing        4 weeks
2003            medications
                continued
                without dose
                modification

Fuangchan       --              4 weeks
et al., 2011

Ooi et al.,     --             4 weeks to
2012                            3 months

Study           Outcome

Dans et al.,    After 3 months, result shows a mean
2007            change difference of 0.22% for the
                hemoglobin A1c value between
                the two groups, with preference
                over M. charantia. group. However,
                having a P value of 0.4825, the
                findings were insignificant

Trakoon-osot    Significant decrement of A1c levels
et al., 2013    was observed at week 8 and 16 of the
                study period in the group treated with
                addition of M. charantia compared
                to placebo (week 8: 0.25 [+ or -] 0.12%,
                P=0.042; week 16: 0.31 [+ or -] 0.15%,
                P=0.044). Also, reduction in the total
                advanced glycation end products
                was displayed by the treated group
                by week 16 with a mean difference
                of 8.22 [+ or -] 3.58 x [10.sup.3] AU/g
                protein (P=0.028) between the two groups

John et al.,    At week 4, no significant changes
2003            in the blood sugar levels and
                fructosamine levels in treatment
                or placebo group were observed

Fuangchan       At week 4, a significant reduction
et al., 2011    in fructosamine was seen in the
                metformin group (-16.8%; 95% CI)
                and the 2000 mg/day bitter melon
                group (-10.2; CI 95%). Whereas
                insignificant reduction was shown
                in the 500 and 1000 mg/day bitter
                melon group (-3.5; 95% CI and
                -10.3; 95% CI). Lowering of fasting
                plasma glucose was not seen by
                bitter melon groups at week 4

Ooi et al.,     In studies with placebo as control,
2012            statistically significant difference was
                not observed between the glycemic
                control with the M. charantia and
                placebo
                Comparison conducted between
                M. charantia and commonly
                prescribed metformin or
                glibenclamide also did not exhibit a
                significant change in glycemic control

CI=Confidence interval, M. charantia=Momordica charantia
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Author:Zainol, Nur Irnawaty; Mahalingam, Sundara Rajan; Ong, Sandy Gim Ming; Arshad, Kamaruddin; Ming, Long
Publication:Archives of Pharmacy Practice
Article Type:Report
Date:Jan 1, 2016
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