Safety and efficacy of herbal tea for patients with diabetes mellitus.
Diabetes is a chronic long-term metabolic disorder which affects the ability of the body to produce enough or use insulin.  As a result, glucose builds up in the bloodstream and cause abnormal high levels of glucose in the blood (hyperglycemia). Uncontrolled diabetes can lead to several potential complications such as heart attack, stroke, kidney disease, limb amputation, depression, anxiety, and blindness. 
The indications for Glucos Cut (GC) Tea are to help prevent excessive sugar intake, reduce the risk of developing type II diabetes, reduce the risk of chronic diseases, regulate the level of blood glucose, and control body weight.  One tea bag of GC Tea should be dipped into 300 ml hot water and it is recommended to be consumed 2-3 times per day. GC Tea consists of five different herbs, i.e., green tea, Gymnema sylvestre, mulberry leaf, rooibos tea, and stevia.  This article will review the safety and efficacy used of GC Tea as well as its medical marketing and regulation.
The electronic databases such as PubMed, ScienceDirect, Google Scholar, and MEDLINE via EBSCOhost were accessed using the following search terms: "Green tea," "rooibos," "gymnema sylvestre," "mulbwwerry," "stevia,", "pharmacokinetics," "pharmacology,", "safety" and "efficacy".
Additional information was searched through the Micromedex, "Medicines (Advertisement and Sales) Act 1956" and the "Guideline on Advertising of Medicines and Medicinal Products to General Public 2006." The search was conducted from September to October 2015.
Of total 28 articles reviewed, only 20 relevant full-text articles were obtained and reviewed.
Green tea contains several active polyphenols such as epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), and epicatechin gallate, with EGCG being the most abundant and possessing the most potent antioxidative activity.  In addition, caffeine, theobromine, theophylline, and phenolic acids such as gallic acids are also present in green tea.  According to Chow et al., the catechins in human plasma reached peak levels in 1.5-2.5 h after consumption of 1.5 g of decaffeinated green tea. Plasma concentration of tea catechins in human is mostly in the sub-[micro]M or nM after oral consumption of green tea as a beverage or as an oral product.  The daily dosing with 800 mg EGCG for 4 weeks increased both maximum plasma concentration and AUC, but no such increase was observed for dose below 400 mg per day.  Over 90% EGC and EC were excreted in urine within 8 h.  EGCG was not detected in urine, thus were assumed to be excreted through bile. 
The major constituents of G. sylvestre are gymnemic acid and gymnema saponins.  There are no many pharmacokinetic studies done for G. sylvestre. Poor lipid solubility and complex structure of gymnemic acid make it difficult to pass through the biomembranes for its absorption in the circulatory 
The three major flavonoids present in mulberry leaf are rutin, isoquercitrin, and astragalin.  In the pharmacokinetics study of mulberry leaves done by He et al., all these three flavonoids were rapidly absorbed and eliminated in rat plasma after oral administration, with their half-life of elimination ranging from 0.87 to 1.19 h. Metabolites of astragalin (i.e., kaempferol) and quercetin (i.e., isorhamnetin) also have been detected in rat plasma after oral administration of total flavonoids from mulberry leaves. 
The most abundant flavonoid in rooibos tea (Aspalathus linearis) is aspalathin, a dihydrochalcone C-glycoside.  Most of the aspalathin metabolites were excreted within 5-12 h of tea consumption, suggesting absorption in the intestine!101 However, rooibos flavonoids have a very low bioavailability based on the absence of detectable amount of its metabolites in blood.  The presence of unchanged flavonoids, especially aspalathin, in plasma could not be confirmed due to its high affinity to albumin. 
Stevia is an herb that is commonly known as sugar leaf or sweet leaf where it is used as a sweetener. As a sugar substitute, stevia has slower onset and longer duration than that of normal sugar.  Stevioside, an abundant component of Stevia rebaudiana leaves, is a hydrophilic diterpenoid glycoside with relatively high molecular weight; therefore, it is unlikely to be absorbed in the intestine unless with the help of bacterial intestinal.  According to Chatsudthipong and Muanprasat, metabolic conversion of stevioside to steviol occurred in liver and was excreted via two routes, biliary and urinary excretion.
Efficacy and safety
In a randomized, double-blind, placebo-controlled trial study about therapeutic effect of high-dose green tea extract on weight reduction by Chen et al., the results show that high-dose green tea extract significantly reduced weight and waist circumference within 12 weeks. There is also a consistent decrease in total cholesterol and low-density lipoprotein (LDL) plasma levels without any adverse effects in women with central obesity.  The mechanism of green tea extract in influencing body weight and body composition is attributed by the effects of EGCG where it increases fat oxidation through inhibition of COMT, an enzyme involved in the degradation of norepinephrine, and through the regulation of lipid metabolism-related genes and transcription factor expression. 
A clinical study was conducted to determine the safety and pharmacokinetics of green tea polyphenols after 4 weeks oral administration of EGCG or Polyphenon E (a decaffeinated green tea polyphenol mixture) in healthy individuals by Chow et al. Findings show that only mild adverse events (Grade 1) were reported such as upset stomach, nausea, heartburn, excess gas, dizziness, headache, and muscle pain. 
In the experimental study done by Persaud et al., G. sylvestre is found to have stimulatory effects on insulin release by increasing membrane permeability. It produces hypoglycemic effects through an unwanted physical mechanism, rather than a physiological one that is by stimulating exocytosis by regulated pathway. [14,15] The phytoconstituents such as gymnemic acid, gymnema saponins, and gurmarin are responsible for sweet suppression activity.  This suppression involved direct interaction with the apical side of the taste cells, possibly by binding to sweet taste receptor. 
In a review article about phytochemicals and pharmacological properties of G. sylvestre done by Tiwari et al., it can be concluded that G. sylvestre is safe when taken in recommended dose. However, symptoms such as hypoglycemia, weakness, shakiness, excessive sweating, and muscular dystrophy may occur when it is consumed in high doses.  Toxic hepatitis and drug-induced liver injury also have been reported in the diabetic patients treated with G. sylvestre. 
A cross-over study was done to assess the effect of drinking rooibos tea on total antioxidant capacity.  Conclusion has shown that acute ingestion of rooibos tea induced an increase in plasma antioxidant defenses in healthy patients. Also, a controlled clinical trial followed a pre-and post-measurement single group intervention design was conducted to investigate the effect of rooibos on biochemical and oxidative stress parameters in adults at risk for cardiovascular disease by Marnewick et al. It is found that rooibos significantly improved lipid profile and redox status, both relevant to heart disease. The results also show that no adverse effects were reported when consuming six cup of rooibos per day for 6 weeks although certain liver (alanine transaminase, aspartate aminotransferase, and alkaline phosphatase) and kidney (creatinine) function indicators were significantly increased. However, the level of these indicators was still within reference range. 
A case-control study was carried out to identify reduction of postprandial hyperglycemia by mulberry tea in type-2 diabetic patients by Banu et al. Findings show a significant decline in the postprandial glucose level after 90 min of mulberry tea consumption. This is probably due to the action of mulberry tea extract (i.e., 1-deoxynojirimycin) on the enzyme a-glucosidase causing delayed in carbohydrate ingestion.  Mulberry leaf extracts also exhibit good antioxidant activity and significantly reduce serum triglyceride and LDL level by 10.6% and 8.2%, respectively (P < 0.05) from baseline. 
In the study done to test the effects of stevia on food intake, satiety, postprandial glucose, and insulin level in both healthy and diabetic patients showed a significant reduction in postprandial glucose and insulin level when compared to sucrose.  According to the review article by Chatsudthipong and Muanprasat, it is found that ingestion of 750 mg/day of stevioside for 3 months produced no adverse effects or abnormalities in liver and renal function tests and serum electrolytes in either healthy individuals or individuals with underlying diseases such as diabetes or hypertension.
GC Tea is categorized as a drinking supplement, which is controlled by the Food Safety and Quality Division, Ministry of Health (MOH). It does not need to be registered with the National Pharmaceutical Control Bureau (NPCB) as only pharmaceutical products or cosmetic products are required to be registered with NPCB. As a health supplement, GC Tea advertisement does not require an approval from the Medicine Advertisements Board (MAB), MOH.
However, any food or drinking supplements are prohibited to make any claims on medical treatment either directly or indirectly in their advertisement. 
According to the MAB guideline, the advertisement of medicines or medicinal products should not contain any claims on prevention, treatment, alleviation, cure, or diagnosis of the disease. GC Tea is a supplement that can help reduce risk of diabetes and chronic diseases as mentioned in the original distributor company website. However, in the advertisement created by local suppliers through online blogs and facebook, GC Tea is claimed to be a cure for diabetes. This act has clearly violated the clause no. 3 (1) in Medicines (Advertisement and Sale) Act 1956 where the party involved, if convicted, may be subjected to a fine not exceeding RM3000 or to imprisonment not exceeding 1 year or to both. 
Although at the upper part of online advertisements, it has the statement that GC Tea is a cure for diabetes, at the lower part of the same advertisements, it is stated in a tiny red font that GC Tea only acts as a drinking supplement and not to be treated as a medicine specifically for cure. These contradict statements in that advertisement will cause confusion among its consumers and will give false information about the true benefits of GC Tea. It is also mentioned in the MAB guideline, clause no. 4.9 where advertisements should not contain any statement or visual presentation which, whether directly or by implication, is likely to mislead the consumer about any product.
Distributor/manufacture company should take full responsibilities by monitoring and advising their local suppliers in term of advertisement. They should clearly inform their local suppliers about the guideline and criteria that must be followed before advertising their product.
How Malaysian society is at risk
Malaysia is a multi-racial country with each race has its own beliefs and cultures. Like other Asian peoples, Malaysians also believe with the use of traditional or herbal medicines to treat illnesses. They are exposed to herbal medicines through internet, media, publications, and friends without being aware of its potential toxicity. 
Most of the people, especially elderly and those poorly educated, believe that herbal medicines are safe because it is a natural product and contains no chemical. The truth is pure herbal medicine contains more chemicals compare to modern medicine as modern medicine is created by extracting only one chemical compound from plants or other organisms. Unlike modern medicines, herbal supplements do not undergo rigorous study and trial to measure its safety and efficacy. Herbal medicine may also be contaminated with substances such as lead, arsenic, mercury, mycobacterium, penicillium, coliforms, salmonella, candida, mouse dropping, earthworms, and blister beetles.  This contamination may cause toxicity to human body.
Search strategies Search item Features Keywords "Green tea," "rooibos," "gymnema sylvestre," "mulbwwerry," "stevia," "pharmacokinetics," "pharmacology," "safety" and "efficacy" Years searched All Total number of 28 articles reviewed Relevant full-text 20 articles reviewed
The use of herbal medicines concurrently with modern medicines could also cause interaction. It may interrupt with the mechanism and pharmacokinetics of modern medicine resulted in reduce efficacy or increase toxicity of modern medicine. For example, Gymnema sylvestre in GC Tea will have interaction with Gliclazide where it will reduce hypoglycemic activity of Gliclazide.  G. sylvestre inhibiting absorption and increasing clearance of Gliclazide resulted in a significant decrease of hypoglycemic effect of Gliclazide. 
Consumption of dietary supplements and herbal medicines are relatively harmless when used appropriately.  The unnecessary and reckless uses of these products are reported to be the reasons that lead to problems.  For example, when herbs and supplements are used for inappropriate indications, or prepared inappropriately, or used in excessive dosages, or used in longer duration, it can cause toxic to human body.  This also applied to GC Tea as mentioned in the safety and efficacy data above; when G. sylvestre is consumed in large dosage, it will cause adverse events such as muscular dystrophy and liver toxicity. 
Based on efficacy data above, it is proved that GC Tea has benefits in reducing risk of diabetes, cardiovascular diseases, and obesity. GC Tea also has antioxidant properties that can help reduce risk of cancer. Only mild adverse effects were reported when consuming these herbs in recommended dose. Therefore, consumption of GC Tea should follow its recommended doses to avoid any unwanted adverse effects.
It is very important to bear in mind that herbal medicines are not effective against serious diseases. GC Tea cannot control diabetes as effectively as modern medicines. To manage diabetes effectively, it needs to be prescribed with anti-diabetic drugs. However, concomitant use of GC Tea with anti-diabetic drugs may reduce efficacy of anti-diabetic drugs. Diabetic patients who are currently on anti-diabetic medications should consult their doctors or pharmacists before consuming GC Tea. Although GC Tea seems to be effective in reducing weight, it is also recommended to balance the food intake and exercise to reduce the body weight. Consumers should not be too dependent on the consumption of GC Tea alone.
Some of the studies mentioned above have a few limitations such as small sample size and short intervention duration. This makes it difficult to assess efficacy and safety for a long-term and to verify the traditional claims made. There are also very few studies on these herbs conducted in human. Most of pharmacokinetics and toxicology data were contributed by the experimental studies done in animals. More researches and investigations in human focusing on double-blind, randomized control trial methodology are needed to ensure the validity and applicability of study results. Long-term efficacy and appropriate dosage for safety should also be considered in the future research.
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.
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Financial support and sponsorship
This work was supported by LESTARI Grant Scheme: 600RMI/DANA 5/3/LESTARI (42/2015). 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.
[1.] American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2004; 27 Suppl 1:S5-10.
[2.] GC Tea. Rashwealth Group, 2015.
[3.] Chow HH, Cai Y, Hakim IA, Crowell JA, Shahi F, Brooks CA, et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res 2003; 9:3312-9.
[4.] Chow HH, Hakim IA. Pharmacokinetic and chemoprevention studies on tea in humans. Pharmacol Res 2011; 64:105-12.
[5.] James KD, Forester SC, Lambert JD. Dietary pretreatment with green tea polyphenol, (-)-epigallocatechin-3-gallate reduces the bioavailability and hepatotoxicity of subsequent oral bolus doses of (-)-epigallocatechin-3-gallate. Food Chem Toxicol 2015; 76:103-8.
[6.] Micromedex Solutions, Truven Health Analytic. 2015.
[7.] Tiwari P, Mishra BN, Sangwan NS. Phytochemical and pharmacological properties of Gymnema sylvestre: An important medicinal plant. Biomed Res Int 2014; 2014:830-285.
[8.] He J, Feng Y, Ouyang HZ, Yu B, Chang YX, Pan GX, et al. A sensitive LC-MS/MS method for simultaneous determination of six flavonoids in rat plasma: Application to a pharmacokinetic study of total flavonoids from mulberry leaves. J Pharm Biomed Anal 2013; 84:189-95.
[9.] Breiter T, Laue C, Kressel G, Groll S, Engelhardt UH, Hahn A. Bioavailability and antioxidant potential of rooibos flavonoids in humans following the consumption of different rooibos formulations. Food Chem 2011; 128:338-47.
[10.] Stalmach A, Mullen W, Pecorari M, Serafini M, Crozier A. Bioavailability of C-linked dihydrochalcone and flavanone glucosides in humans following ingestion of unfermented and fermented rooibos teas. J Agric Food Chem 2009; 57:7104-11.
[11.] Uchiyama H, Tozuka Y, Imono M, Takeuchi H. Transglycosylated stevia and hesperidin as pharmaceutical excipients: Dramatic improvement in drug dissolution and bioavailability. Eur J Pharm Biopharm 2010; 76:238-44.
[12.] Chatsudthipong V, Muanprasat C. Stevioside and related compounds: Therapeutic benefits beyond sweetness. Pharmacol Ther 2009; 121:41-54.
[13.] Chen IJ, Liu CY, Chiu JP, Hsu CH. Therapeutic effect of high-dose green tea extract on weight reduction: A randomized, double-blind, placebo-controlled clinical trial. Clin Nutr 2015. pii: S0261-561400134-X.
[14.] Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinol 1999; 163:207-12.
[15.] Ezuruike UF, Prieto JM. The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations. J Ethnopharmacol 2014; 155:857-924.
[16.] Villano D, Pecorari M, Testa MF, et al. Unfermented and fermented rooibos teas (Aspalathus linearis) increase plasma total antioxidant capacity in healthy humans. Food Chem 2010; 123:679-83.
[17.] Marnewick JL, Rautenbach F, Venter I, Neethling H, Blackhurst DM, Wolmarans P, et al. Effects of rooibos (Aspalathus linearis) on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease. J Ethnopharmacol 2011; 133:46-52.
[18.] Banu S, Jabir NR, Manjunath NC, Khan MS, Ashraf GM, Kamal MA, et al. Reduction of post-prandial hyperglycemia by mulberry tea in type-2 diabetes patients. Saudi J Biol Sci 2015; 22:32-6.
[19.] Aramwit P, Supasyndh O, Siritienthong T, Bang N. Mulberry leaf reduces oxidation and C-reactive protein level in patients with mild dyslipidemia. Biomed Res Int 2013; 2013:787981.
[20.] Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite 2010; 55:37-43.
[21.] Guidelines On Advertising of Medicines and Medicinal Products To General Public. MAB 3/2015 ed; 1 September, 2015.
[22.] Medicines (Advertisement And Sale) Act 1956. 2006.
[23.] Chalut D. Toxicological risks of herbal remedies. Paediatr Child Health 1999; 4:536-8.
[24.] Dholi SK, Raparla R, Kannappan. Effect of Gymnema Sylvestre on the pharmacokinetics and pharmacodynamics of gliclazide in diabetic rats. Am J Phytomed Clin Therap 2013; 1.
[25.] Phua DH, Zosel A, Heard K. Dietary supplements and herbal medicine toxicities-when to anticipate them and how to manage them. Int J Emerg Med 2009; 2:69-76.
Siti Syarihan Abdullah (1), Ali Saleh Alkhoshaiban (1,2), Vasudevan Mani (3), Muhammad Eid Akkawi (4), Long Chiau Ming (1,5)
(1) Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, (5) Vector-borne Diseases Research Group (VERDI), Pharmaceutical and Life Sciences CoRe, Universiti Teknologi MARA, Selangor, (4) Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan, Malaysia, (2) College of Medicine, (3) College of Pharmacy, Qassim University, Buraidah, Saudi Arabia
Address for correspondence:
Dr. Long Chiau Ming, Level 11, FF1 Building, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor, Malaysia. E-mail: firstname.lastname@example.org
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|Author:||Abdullah, Siti Syarihan; Alkhoshaiban, Ali Saleh; Mani, Vasudevan; Akkawi, Muhammad Eid; Ming, Long|
|Publication:||Archives of Pharmacy Practice|
|Date:||Jan 1, 2016|
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