Diabetes is a group of metabolic diseases in which a person has high blood sugar. This high blood sugar produces the symptoms of frequent urination, increased thirst, and increased hunger. Untreated, diabetes can cause many complications. Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. Serious long-term complications include heart disease, kidney failure, and damage to the eyes. Thus, I am looking for some new natural products to test them as anti-diabetic remedy in an animal model.
Vijayendra:
Glad to help. Fenugreek is a good choice, but just here are a few tips culled from review:
(1) Only trials that administered Fenugreek seed powder in upper dose range (>= 5g) achieved a significant reduction in glucose parameters to a clinically releevant degree;
(2) Low doses (< 2 g) of hydro-alcoholic extracts were ineffective;
(3) The upper dose range that includes doses from 5 - 25 g of fenugreek seed powder provided an additional benefit, of also lowering postprandial glucose levels, again to a clinically releevant degree; this was true of fenugreek raw seeds, extracted seed powder, cooked seeds (dosed at 25 g) and gum isolate of seeds (dosed at 5 g) while degummed seeds (even up to 25 g) had negligible effect.
EVIDENCE-BASED HERBAL AGENTS FOR DIABETES
Despite highly preliminary but inconsistent data for many herbals and spices (such as Cinnamon, Hoodia, Ginseng, Garlic, Ginkgo, Aloe, among many many others), a review of the most robust and critically appraised data to date, methodologically assessed and with cross-confirmation [1-5], finds the highest level of evidence to support just four CAM agents (all Ayurvedic components):
1. Silybum marianum (Silymarin),
2. Trigonella foenum-graecum (Fenugreek),
3. Momordica charantia (Bitter Melon),
4. Gymnema sylvestre).
Below is a brief summary of my review:
A meta-analysis of nine randomized, placebo-controlled trials [1] suggests that supplementation with Silybum marianum (Silymarin), and Trigonella foenum-graecum (Fenugreek) (and with somewhat more provisional evidence, Ipomoea batatas (Sweet Potato)) may improve glycemic control in type 2 diabetes, an effect not consistently nor robustly observed with Cinnamomum cassia (Cinnamon). This has been confirmed, along with strong evidence for Trigonella foenum-graecum (Fenugreek) , Momordica charantia (Bitter Melon), Gymnema sylvestre and Silybum marianum (Silymarin/Milk Thistle) [2-5].
Trigonella foenum-graecum
Human clinical studies [6-14] have shown benefit from fenugreek seeds has been reported in management of both T1D and T2D, with reduction of FBG, TG, total cholesterol, LDL, VLDL, LVDL, glucoseuria, increase HDL level and percent of insulin sensitivity, and improve 24 h urinary glucose output, and favorably effect glycemic index of food, glucose tolerance, fasting glucose and dyslipidemia and triglycerides.
Momordica charantia
Momordica charantia (Karela, Ampalaya, Bitter Melon) significantly decreases PPBG and FBG levels, significantly improve glucose tolerance maturity onset diabetic patients (17), and reduces mean blood glucose and HbA1c [15-20;22]. And the effects of M. charantia and rosiglitazone, the well-known thiazolidinedione derivative were compared [21], showing that M. charantia was more effective in the management of diabetes (FBG, total cholesterol and serum sialic acid) and its related complications (retinopathy and myocardial infarction) than rosiglitazone, although the hypoglycemic effect of M. charantia may be less than metformin [23].
Gymnema sylvestre
Accumulating evidence [24-28] demonstrates that Gymnema sylvestre (Gurmar, Meshashringi, Merasingi, Kavali, Dhuleti) can improve glycemic control in diabetes, significantly decreasing FBG, PPBG, HbA1c and serum lipids, accompanied by increases in circulating insulin and C-peptide, and in addition stimulating insulin secretion from isolated human islets of Langerhans.
Silybum marianum
S. marianum and its flavonolignans (silymarin) has been shown to reduce glucose and lipids, FBG, HbA1c, total cholesterol, LDL, TG, glucosuria, and the hepatic enzymes serum glutamic oxalacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in T2D patients [29-32]. In addition, silymarin administration in diabetic patients with liver disease reduces insulin resistance, endogenous insulin production and need for exogenous insulin administration [33-35].
METHODOLOGY OF THE REVIEW
A search of the PUBMED, Cochrane Library / Cochrane Register of Controlled Trials, MEDLINE, EMBASE, AMED (Allied and Complimentary Medicine Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, ISI Web of Science (WoS), BIOSIS, LILACS (Latin American and Caribbean Health Sciences Literature), ASSIA (Applied Social Sciences Index and Abstracts), and SCEH (NHS Evidence Specialist Collection for Ethnicity and Health) was conducted without language or date restrictions, and updated again current as of date of publication, with systematic reviews and meta-analyses extracted separately. Search was expanded in parallel to include just-in-time (JIT) medical feed sources as returned from Terkko (provided by the National Library of Health Sciences - Terkko at the University of Helsinki). Unpublished studies were located via contextual search, and relevant dissertations were located via NTLTD (Networked Digital Library of Theses and Dissertations) and OpenThesis. Sources in languages foreign to this reviewer were translated by language translation software.
REFERENCES
1. Suksomboon N1, Poolsup N, Boonkaew S, Suthisisang CC. Meta-analysis of the effect of herbal supplement on glycemic control in type 2 diabetes. J Ethnopharmacol. 2011 Oct 11;137(3):1328-33. Epub 2011 Aug 5.
2. Cefalu WT, Stephens JM, Ribnicky DM. Authors. Diabetes and Herbal (Botanical) Medicine. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press; 2011. Chapter 19.
3. Chang CL, Lin Y, Bartolome AP, Chen YC, Chiu SC, Yang WC. Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat Med 2013; 2013:378657.
4. Pothuraju R1, Sharma RK, Chagalamarri J, Jangra S, Kumar Kavadi P. A systematic review of Gymnema sylvestre in obesity and diabetes management. J Sci Food Agric. 2014 Mar 30;94(5):834-40. Epub 2013 Nov 19.
5. Perera PK, Li Y. Functional herbal food ingredients used in type 2 diabetes mellitus. Pharmacogn Rev 2012; 6(11):37-45.
6. SHARMA, R.D.; RAGHURAN, T.C. RAO, N.S. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur. J. Clin. Nutr 1990, v.44, p.301-306..
7. KASSAIAN, N.; AZADBAKHT, L.; FORGHANI, B.; AMINI, M. Effect of fenugreek seeds on blood glucose and lipid profiles in type 2 diabetic patients. Int. J. Vitam. Nutr. Res 2009., v.79, p.34-39.
8. SHARMA, R.D.; RAGHURAN, T.C. Hypoglycaemic effect of fenugreek seeds in non-insulin dependent diabetic subjects. Nutr. Res. 1990, v.10, p.731-739.
9. ISMAIL, M.Y.M. Clinical evaluation of antidiabetic activity of Trigonella seeds and Aegle marmelos leaves. World Appl. Sci. J. 2009, v.7, p.1231-1234.
10. FU-RONG, L.; LIN, S.; YOU, Q.; LAN, G.; HENG, L.; YI, D. Clinical observation on Trigonella foenum-graecum L. total saponins in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Chin. J. Integr. Med., v.14, p.56-60, 208.
11. GUPTA, A.; GUPTA, R.; LAL, B. Effect of Trigonella foenum- graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J. Assoc. Physicians India 2001, v.49, p.1057-1061.
12. SHARMA, R.D. Effect of fenugreek seeds and leaves on blood glucose and serum insulin responses in human subjects. Nutr. Res. 1986, v.6, p.1353-1364.
13. ABDEL-BARRY, J.A.; ABDEL-HASSAN, I.A.; JAWAD, A.M.; Al-HAKIEM, M.H. Hypoglycaemic effect of aqueous extract of the leaves of Trigonella foenum-graecum in healthy volunteers. East Mediterr. Health J. 2000, v.6, p.83-88..
14. Gopalpura P.B, Jayanthi C, Dubey S. Effect of Trigonella foenum-graecum seeds on the glycemic index of food: A clinical evaluation. Int J Diab Dev Ctries. 2009;27:41–5.
15. GROVER, J.K.; GUPTA, S.R. Hypoglycemic activity of seeds of Momordica charantia. Eur. J. Pharmacol. 1990, v.183, p.1026-1027.
16. AHMAD, N.; HASSAN, M.R.; HALDER, H.; BENNOOR, K.S. Effect of Momordica charantia (Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients. Bangladesh Med. Res. Counc. Bull. 1999, v.25, p.11-13.
17. WELHINDA, J.; KARUNANAYAKE, E.H.; SHERIFF, M.H.H.; JAYASINGHE, K.S.A. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. J. Ethnopharmacol. 1986, v.17, p.277-282.
18. SIRVASTAVA, Y.; VENKATAKRISHNA-BHATT, H.; VERMA, Y.; VENKAIAH, K. Antidiabetic and adaptogenic properties of Momordica charantia extract: An experimental and clinical evaluation. Phytother. Res. 1993, v.7, p.285-289.
19. LEATHERDALE, B.A.; PANESAR, R.K.; SINGH, G.; ATKINS, T.W.; BAILEY, C.J.; BIGNELL, A.H.C. Improvement in glucose tolerance due to momordica charantia (karela). Brit. Med. J. 1981, v.282, p.1823-1824.
20. WAHEED, A.; MIANA, G.A.; SHARAFATULLAH, T.; AHMAD, S.I. Clinical investigation of hypoglycemic effect of unripe fruit on Momordica charantia in type-2 (NIDDM) diabetes mellitus. Pakistan J. Pharmacol. 2008, v.25, p.7-12.
21. RAHMAN, I.; MALIK, S.A.; BASHIR, M.; KHAN, R.; IQBAL, M. Serum sialic acid changes in non-insulin-dependant diabetes mellitus (NIDDM) patients following bitter melon (Momordica charantia) and rosiglitazone (Avandia) treatment. Phytomed. 2009, v.16, p.401-405.
22. FUANGCHAN, A.; SONTHISOMBAT, P.; SEUBNUKARN, T.; et al. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J. Ethnopharmacol. 2011, v.134, p.422-428.
23. BALDWA, V.S.; BHANDARI, C.M.; PANGARIA, A.; GOYAL, R.K. Clinical trial in patients with diabetes mellitus of an insulin-like compound obtained from plant source. Upsala J. Med. Sci. 1977, v.82, p.39-41.
24. SHANMUGASUNDARAM, E.R.B.; RAJESWARI, G.; BASKARAN, K.; KUMAR, B.R.R.; SHANMUGASUNDARAM, K.R.; AHMATH, B.K. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J. Ethnopharmacol. 1990, v.30, p.281-294.
25. BASKARAN, K.; AHAMATH, .K.; SHANMUGASUNDARAM, K.R.; SHANMUGASUNDARAM, E.R.B. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J. Ethnopharmacol. 1990, v.30, p.295-305.
26. JOFFE, D.J.; FREED, S.H. Effect of extended release Gymnema sylvestre leaf extract alone or in combination with oral hypoglycemics or insulin regimens for type 1 and type 2 diabetes. Diabetes Control Newsletter 2001, v.76, p.30.
27. AL-ROMAIYAN, A.; AL-ROMAIYAN, A.; LIU, et al. A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro. Phytother. Res. 2010, v.24, p.1370-1376.
28. Paliwal, R.; Kathori, S.; Upadhyay, B. Effect of Gurmar (Gymnema sylvestre) powder intervention on the blood glucose levels among diabetics. Ethno-Med. 2009, v.3, p.133-135.
29. DIXIT, N.; BABOOTA, S.; KOHLI, K.; AHMAD, S.; ALI, J. Silymarin: a review of pharmacological aspects and bioavailability enhancement approaches. Indian J. Pharmacol. 2007, v.39, p.172-179.
30. FALLAH HOSEINI, H.; LARIJANI, B.; HESHMAT, et al. The efficacy of Silybum marianum (L.) gaertn. (Silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother. Res. 2006, v.20, p.1036-1039.
31. RAMEZANI, M.; AZAR ABADI, M.; FALAH HOSSEINI, H.; ABDI, H.; BAHER, G.R.; HOSSEINI, M.A.S. The effect of Silybum marinum (L.) gaertn. Seed extract on glycemic control in type II diabetic patient's candidate for insulin therapy visiting endocrinology clinic in Baqiyatallah hospital in the years of 2006. J. Med. Plants 2008, v.7, p.79-84.
32. HUSSAIN, S.A.R. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J. Med. Food. 2007, v.10, p.543-547.
33. JOSE, M.A.; ABRAHAM, A.; NARMADHA, M.P. Effect of silymarin in diabetes mellitus patients with liver disease. J. Pharmacol. Pharmacother. 2011, v.2, p.287-289.
34. VELUSSI, M.; CERNIGOI, A.M.; DE, MONTE, A.; DAPAS, F.; CAFFAU, C.; ZILLI, M. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J. Hepatol. 1997, v.26, p.871-879.
35. VELUSSI, M.; CERNIGOI, A.M.; VIEZZOLI, L.; DAPAS, F.; CAFFAU, C.; ZILLI, M. SILYMARIN reduces hyperinsulinemia, malondialdehyde levels, and daily insulin needs in cirrhotic diabetic patients. Curr. Ther. Res. 1993, v.53, p.533-545.
We have been using Fenugreek powder to treat diabetes. Its highly effective.
Thnx Constantine for the informative answer!
Vijayendra:
Glad to help. Fenugreek is a good choice, but just here are a few tips culled from review:
(1) Only trials that administered Fenugreek seed powder in upper dose range (>= 5g) achieved a significant reduction in glucose parameters to a clinically releevant degree;
(2) Low doses (< 2 g) of hydro-alcoholic extracts were ineffective;
(3) The upper dose range that includes doses from 5 - 25 g of fenugreek seed powder provided an additional benefit, of also lowering postprandial glucose levels, again to a clinically releevant degree; this was true of fenugreek raw seeds, extracted seed powder, cooked seeds (dosed at 25 g) and gum isolate of seeds (dosed at 5 g) while degummed seeds (even up to 25 g) had negligible effect.
Dear kaniklidis, tqvm for your review, it is really very helpful and fantastic. Actually in my country we use some of our local herb and plant such as turnip seed, powdered walnut tree leaf, bitter melon, and shorabi (I do not know the name in english). TQ
Rahman:
Yes, bitter melon is also an excellent choice (in addition to Fenugreek) - I discussed it above in my posting, under it's botanical name Momordica charantia, also known as Karela or Ampalaya, or in Malaysia as Peria Katak.
In my country, cameroon, vernonia sp are the famous one to attenuate diabetes secondary effects
Mireille:
Good observation, there is increasing evidence of Vernonia's potential antidiabetic properties which I've studied and reviewed, including a just reported randomized placebo-controlled trial [6]; see below:
VERNONIA (BITTERLEAF) ANTIDIABETIC ACTIVITY
Vernonia amygdalina (Del.) is commonly called bitter leaf (or Bitterleaf) and is the most widely cultivated species of the genus Vernonia, belonging to the family Astaraceae, itself having about 1,000 species of shrubs, popular in most of West Africa countries, especially Cameroon (known as Ndole, or sometimes muop) where the stem and root divested of the bark are used as chewsticks, and also in Nigeria, Gabon, Ghana, the Congo Democratic Republic and the Central African Republic [1,2,3]. In Cameroon the leaves of Vernonia amygdalina are the most consumed vegetables (Ndole) for special occasions (marriage, baptism, Christmas, birthday, funeral). Vernonia has pharmacologic activities that include but are not limited to hypoglycemic, antidiabetic, antimalarial, hypolipidemic, anti-inflammatory, and anti oxidant activities, and there is now growing preclinical data suggesting a potentially significant anticancer role, especially in breast and prostate cancer [4,5].
Although until very recently, the data in support of positive antidiabetic benefit was restricted to preclinical studies, we now (2013) have a randomized placebo-controlled crossover trial [6] of a Vernonia extract for the treatment of Type 2 Diabetes (T2D), finding that the extract (2g three times daily) induced significant reductions in fasting blood glucose, hemoglobin A1c, and on blood cholesterol profile (LDL cholesterol, and triglyceride levels), probably from the n-hexadecanoic acid component of Vernonia along with other flavonoids with antioxidants, and without any adverse effects on liver or kidney function during 6 months of therapy. It is likely therefore that both higher doses and long duration would be safe and may yield still more powerful antidiabetic effects.
One possible caution: Thomas Makon with the Laboratoire de Chimie Théorique et Physique at the Université de Yaoundé I in Yaoundé, Cameroun, and colleagues have found in a recent study [7] that there may be low-level exposure arising from naturally occurring radionuclides in three types of Vernonia (Amygdalina; Calvoana and Richardiana) cultivated in Cameroon, with the AED (Annual Effective Dose) being zero for both radionuclides (uranium and thorium) in the North-west (like the city of Bamenda/Abakwa). This is probably due to the fact that North-west Cameroon contains of a large number of mountains in the midst of old volcanoes (remember the Lake Nyos eruption in 1986), resulting in possible radionuclides depositions being transported through the erosion process to the South and South-west which are located almost at the sea level. But although there could theoretically be mutagenic and carcinogenic effects from these radionuclides, a close reading of the findings which I undertook show that the AED values were within IAEA acceptable limits, and in addition the highest levels were found in the calvoana and richardiana types, while Vernonia amygdalina had the lowest levels.
REFERENCES
1. Mbinglo SB. Student Project Report for Natural Resource Institute. United Kingdom/Dschang University Cameroon; Chatham: 1998. Survey on the Production of Bitterleaf Vernonia spp. in Bamenda, N.W. Cameroon.
2. Audu SA, Taiwo AE, Ojuolape AR. A Study Review of Documented Phytochemistry of Vernonia amygdalina (Family Asteraceae) as the Basis for Pharmacologic Activity of Plant Extract. J Natural Sci Res 2012; 2(7).
3. Yedjou CG, Izevbigie EB, Tchounwou PB. Vernonia amygdalina-Induced Growth Arrest and Apoptosis of Breast Cancer (MCF-7) Cells. Pharmacol Pharm 2013 Jan 1; 4(1).
4. Wong FC, Woo CC, Hsu A, Tan BK. The anti-cancer activities of Vernonia amygdalina extract in human breast cancer cell lines are mediated through caspase-dependent and p53-independent pathways. [PLoS One 2013; 8(10):e78021.
5. Davis H, Tane P, Kimbu SF, et al. In vitro anti-prostate cancer and ex vivo antiangiogenic activity of Vernonia guineensis Benth. (Asteraceae) tuber extracts. J Ethnopharmacol 2012 Jun 14; 141(3):866-71.
6. Bin Sayeed MS, Mostofa AG, Ferdous FM, Islam MS. A randomized, placebo-controlled, crossover study of an herbal preparation containing Vernonia cinerea in the treatment of type 2 diabetes. J Altern Complement Med 2013; 19(9):767-71.
7. Makon TB, Nemba RM, Tchokossa P. Investigation of Gamma-Emitting Natural Radioactive Contents in Three Types of Vernonia Consumed in Cameroon. World J Nucl Sci Technol 2011; 1(2):37-45.
In India Fenugreek seeds (called Methi in Hindi) and bitter gourd (also called Karela in Hindi) are used for lowering the glucose level. They have proved to be very useful in this regard.
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