Jou?7&al ofEthnophamacology, 29 (1990) 1- 11 Elsevier Scientific Publishers Ireland Ltd.
AYURVEDIC TREATMENT OF OBESITY: DOUBLE-BLIND, PLACEBO-CONTROLLED
PRAKASH
PARANJPEb,
PRALHAD
PATKI’
A RANDOMISED CLINICAL TRIAL
and BHUSHAN
PATWARDHAN”
“Interdisciplinary School of Ayurvedic Medicine, University of Poona, Pune 411-007, bObesity Clinic, Nanal Hospital, Pune 411-004 and ‘Byramjee Jeejeebhoy Medical College, Pune 411-001 (Indial (Accepted October 16.1989)
Summary
Seventy obese subjects were randomised into four groups. Ayurvedic drug treatments were given for three months while one group received a placebo. Physical, clinical and pathological investigations were carried out at regular intervals. A significant weight loss was observed in drug therapy groups when compared with the placebo. Body measurements such as skin fold thickness and hip and waist circumferences were significantly decreased. Decreases in serum cholesterol and triglyceride levels were observed. No side effects of any kind were observed during the treatment period.
Introduction
Obesity is an important disorder associated with a number of potentially fatal diseases such as adult-onset diabetes mellitus and ischemic heart disease. Treating obesity has become a problem since safe drugs are not available for long-term therapy. Amphetamines have a well-defined abuse potential and drugs like diethylpropion and fenfluramine cause appreciable undesirable sympathomimetic side effects, pulmonary hypertension and depression (Galloway et al., 1984). Thyroid hormones were once used to treat obesity but are now contraindicated due to their untoward systemic effects (Kyle et al., 1966). There is a clear need for a safer drug for long-term therapy of obesity (Stunkard et al., 1980). The development of a non-toxic compound with a capacity to hold weight gain in check is much needed. Ayurveda is the ancient science of life. In the Sanskrit language, “Ayu” means life and “Veda” means the knowledge. This branch of medicine has a 5000-year record of use in the Indian system of medicine. The concepts and Correspondence
to: B. Patwardhan.
0378-8741/$04.20 0 1990 Elsevier Published and Printed in Ireland
Scientific Publishers
Ireland Ltd.
2
treatment of most of the diseases have been described beautifully and in great depth. Ayurvedic classics such as the Charak Samhita and Sushrut Samhita are still followed critically by Ayurvedic physicians in India. Obesity is referred to as “Medoroga” and is considered to be a disease of “Medadhatu” meaning a disorder of lipid metabolism. A variety of different types have been detailed in the Ayurvedic classics along with the treatment for the same. The basic concepts of obesity according to Ayurveda would be a separate topic by itself and hence will not be discussed here (Charak Samhita, 19491. The indigenous drugs described by Ayurveda are comparatively safe and have been used for many years. Drugs such as Triphala guggul, Sinhnad guggul, Gokshuradi guggul and Chandraprabha vati are claimed to be effective in the treatment of obesity (Sharangdhar Samhita, 19841 but their effectiveness has not been tested in controlled clinical trials. Therefore, we undertook a randomized, double-blind, placebo-controlled clinical trial of these agents in the treatment of obesity. Materials and methods A yurvedic medicines Composition of the four formulations are detailed in Table 1 and were obtained from the well-established company of Ayurved Rasashala of Pune which has a valid drug license issued by the Government. The authenticity of each plant and mineral component was established by the Quality Control Laboratory of the company, is also certified by the Government. All tests of identification were carried out by a qualified chemist approved by the Food and Drug Administration. Clinical studies Seventy subjects referred to the obesity clinic were entered into the trial. All were at least 20% in excess of their ideal body weight as defined by the Life Insurance Corporation of India’s height and weight recommendations. At the time of entry into the study, they had a stable weight and none was receiving any drug to reduce their weight. All were in good health and biochemically euthyroid and non-diabetic. None of them had any endocrine disorders. Their characteristics of entry are recorded in Tables 2 and 3. Serum cholesterol was determined using the method of Annan and Isherwood (19691. HDL cholesterol and serum triglycerides were determined by the methods of Chiamori and Henry (19591 and Van Handel et al. (19571. Individuals were divided randomly into four groups, namely Group I to Group IV. Treatment was planned according to Ayurvedic concepts and Triphala guggul was given to all patients in all groups except the placebo group (Group III). Other drugs given were Gokshuradi guggul (Group 11, Sinhanad guggul (Group II) and Chandraprabha vati (Group IV). Individuals in Group III received a 250-mg placebo tablet indistinguishable from the other formulations (Table 1). The subjects were interviewed individually with respect to diet and exercise
3 TABLE
1
COMPOSITION Local name
OF THE AYURVEDIC
FORMULATIONS
Scientific name
Triphala guggul ISharangdhar SamhitaI (250 mg tablet, three times a day, with lukewarm water before meals) Terminalia chebula Retz. Hirda (Combretaceael Terminalia belerica Roxb. Beheda Amalaki Pippali Guggul
(Combretaceael Emblica officinalis Gaertn. (Euphorbiaceael Piper longum Linn. (Piperaceael Commiphora mukul Hook ex Stocks (Burseraceael
Gokshuradi guggul (Sharangdhar SamhitcLI (250 mg tablet, three times a day, with lukewarm water, before meals) Tm’bulus terrestris Linn. Gokharu (Zygophyllaceael Commiphora mukul Guggul Hook ex Stocks (Burseraceael Shunth Zingiber officinale Roscoe (Zingiberaceael Piper nigrum Linn. Mire (Piperaceael Pippali Piper longum Linn. Hirda Beheda Amalaki Nagarmotha
(Piperaceael Terminalia chebula Retz. (Combretaceael Terminalia belerica Roxb. (Combretaceael Emblica officinalis Gaerth. (Euphorbiaceael Cyperus rotundus Linn. Excipients
AND PLACEBO Plant parts
Weight per tablet (mgl
Dried fruit
28
Dried fruit
28
Dried Fruit
28
Dried unripe fruit Gum oleoresin
28
Dried fruit Gum oleoresin
138
170 35
Root
5
Dried unripe fruit Dried unripe
5 5
fruit Dried fruit
5
Dried fruit
5
Dried fruit
5
Rizome
5 10
Dried fruit
10
Dried fruit
10
Dried fruit
10
(Mineral) Seed oil
15 40
Sinhanad guggul (Bhaishaj Ratnawalil (100 mg tablet, three times a day, with lukewarm water, before meals) Hirda Terminalia chebula Retz. Kombretaceael Terminalia belerica Beheda Roxb. (Combretaceael Em blica officinalis Amalaki Gaertn. (Euphorbiaceael Gandhak Sulphur, purified Ricinus communis Erandsneha Linn. (Euphorbiaceael
4 TABLE
1 (continued)
Local name
Scientific
Guggul
Commiphora mukul Hook ex Stocks
name
Plant
parts
Gum oleoresin
Weight per tablet (mgl
15
(Burseraceael Chandraprabhavati Kharangdhar Samhital (250 mg tablet, three times a day, with lukewarm Vavding Shunth Mire Pippali Pippalmool Vekhand Deodar Gajapippali Ativisha Nagarmotha Hirda Beheda Amalaki Chavak Chitrak Kachora Kadechirait Halad Saindhav Padelon Jawkhar Bidlon
water,
before meals) Embeliar ribes Burm. (Myrsinaceael Z&giber officinale Roscoe (Zingiberaceael Piper nigrum Linn. (Piperaceael Piper longum Linn. (Piperaceael Piper longum Linn. (Piperaceael Acorus calamus Linn. (Araceael Cedrus deodara Roxb., Loud. (Pinaceael Scindapsus officinalis Schott. (Araceael Aconitum he teroph yllum. Wall. (Ranunculaceael Cyper-us rotundus Linn. (Cyperaceael Terminalia chebula Retz. (Combretaceael Terminalia belerica Roxb. (Combretaceael Emblica officinalis Gaertn. (Euphorbiaceael Piper officinarum Cas D.C. (Piperaceael Plumbago teylanica Linn. (Plumbaginaceael Curcuma zedoria Rose. (Zingiberaceael Swertia chirata Buch Ham. (Gentianaceael Curcuma longa Linn. (Zingiberaceael Rocksalt, sodium chloride Sodium sulphate Impure carbonate of potash, potassium carbonate Black salt, sodium chloride
Dried
fruit
1.8
Rizome
1.8
Dried unripe fruit Dried unripe fruit Root
1.8
Rizome
1.8
Stem
1.8
Dried
fruit
1.8 1.8
1.8
Rizome
1.8
Rizome
1.8
Dried
fruit
1.8
Dried
fruit
1.8
Dried
fruit
1.8
Stem
1.8
Root
1.8
Rizome
1.8
Stem
1.8
Rizome
1.8
(Salt) (Salt) (Salt)
1.8 1.8 1.8
(Salt)
1.8
5 TABLE 1 (continued) Local name
Gulvel Daruhalad Dhane Sajjikshar Dalchini Elaichi Tamalpatra Nishottar
Plant parts
Tinospora
Stem
1.8
Rizome
1.8
Dried fruit
1.8
(Salt)
1.8
Stem skin
7.2
Dried fruit
7.2
Leaves
7.2
Root
7.2
Root
7.2
Gum
7.2
cordifolia
(Willd.1 Mires. (Menispermaceaei Berberis aristata D.C. (Berberidaceae) Coriandrum sativum Linn. 0Jmbelliferael Impure carbonate of soda, sodium carbonate Cinnamomum ze ylunicum Blume. (Lauraceael Elettaria cardamomum Maton. (Zingiberaceae) Cinnomomum cassia Blume. (Lauraceael Operculina turpethum R.Br. (Convolvulaceael Boliospermum
Danti Vanshalochan Lohabhasma Khadisakhar Shilajit Guggul Placebo
Scientific name
montanum
Muell-Arg. (Euphorbiaceael Barn busa arundinacia Willd (Gramineael Ferrous sulphate Sucrose Asphalt Commiphora mukul Hook ex Stocks (Burseraceael Excipients
(Mineral) (Carbohydrate) (Mineral) Gum oleresin -
Weight per tablet (mgl
14.4 28.8 57.6 57.6 1.6
tablet
(250 mg tablet, three times a day, with lukewarm water, before meals) Charcoal, I.P. Lactose Excipients
(Carbon) (Carbohydrate)
125 100 25
and were advised suitably. Dietary intake was not controlled. The treatment was continued for a period of three months and patients were examined every two weeks. During these visits their body weight, skinfold thickness, body measurements such as waist and hip circumference, blood pressure, temperature, pulse rate and other clinical examinations were carried out. Subjective findings such as increased or decreased appetite, feeling of lightness, sweating, breathlessness, joint pain, etc. were individually noted. Side effects of the drugs, if any, were carefully noted down. On entry and at the end
CHARACTERISTICS
52.6 +
2.6
54.6 ?
6.2
156.6 2 12.0
142.6 2 10.6
Group II 197.0 * 20.0
186.8 f
Serum cholesterol (mg%) Triglycerides (mg%) HDL cholesterol (mg%)
ON ENTRY
30.0
Group I
Description
5.2 2.7 6.0 2.8 3.0 8
88.0 + 4
16 2110 71.2 + 16.8 ? 87.6 2 100.0 + 86.6 2 128.0 “_
Group II
4.5 3.4 6.4 2.4 3.2 4
90.0 2 2
119 76.8 f 19.6 f 91.3 f 104.0 f 84.2 ? 138.0 “_
22
Group III
listed.
50.4 +
160.6 ?
2.4
6.4
188.8 ? 32.0
Group III
were noted between the four groups for the three determinations
OF THE SUBJECTS
86.0 + 2
Figures are mean + S.D. No significant differences
BIOCHEMICAL
TABLE 3
(mmHg)
Pulse rate (per minute) Systolic blood pressure (mmHg) Diastolic blood pressure
6.2 1.6 4.6 3.6
82.4 f 2.4 140.0 2 6
16 2111 76.6 2 18.4 ” 89.4 + 102.0 +
Number of subjects Male/female
Body weight (kg) Skin-fold thickness (mm) Waist circumference (cm) Hip circumference (cm)
Group I
Description
ON ENTRY
were noted between the four groups for the parameters
OF THE SUBJECTS
SD. No significant differences
CHARACTERISTICS
Figures are mean f
CLINICAL
TABLE 2
listed.
51.8 2
150.6 -t
190.6 f
Group IV
7.4
7.6
30.0
90.0 % 2
16 l/12 68.2 rt_ 4.6 20.8 f 4.1 86.4 ? 7.1 105.0 f 2.6 80.2 f 6.0 136.0 2 4
Group IV
of the study, biochemical investigations such as haemogram, tions, serum lipoproteins and cholesterol were estimated. The results were analysed by Student’s t-test.
urine examina-
Results Forty-eight subjects completed the study and there were 22 dropouts during the course of study. The dropouts were mainly from the placebo group who felt that they were not getting any benefit from the therapy. Ten subjects from the active drug groups dropped out due to a variety of reasons, including domestic and family problems (Table 4). A significant weight loss was seen in Groups I, II and IV compared to the placebo group. However, weight losses among I, II and IV were not significantly different from each other (Table 51. None of the patients in the study reported loss of appetite. Skin fold thickness and circumference of the hips and the waistline were significantly decreased as compared to the placebo group P< 0.011. There was a remarkable reduction in serum cholesterol and triglyceride levels in subjects receiving the medicaments as compared to placebo (Table 61. Subjective improvements, such as feelings of well being and lightness and decreased joint pain, appeared to be associated with the non-placebo but could not be statistically documented as significant. Minor side effects like mild diarrhoea and nausea were observed (8 in the drug therapy groups and 2 in the placebo group) but did not necessitate withdrawal of drug therapy. Discussion Obese patients are notorious defaulters (Silverstone and Soloman, 19651. In the present study, efforts were made to retain the interest and co-operation of those taking part in the study and therefore very few defaulted. In the present study, Ayurvedic drugs were given to an unselected group of obese objects. All three Ayurvedic treatments resulted in significant losses of weight relative to the placebo. It appears that treatment with these drugs can produce a clinically significant weight reduction. The reduction in skin fold thickness and hip and waist circumferences were significantly greater in drugtreated individuals as compared to placebo. The treatment did not produce any significant changes in the pulse rate, body temperature and systolic/diastolic blood pressures, indicating that these drugs do not affect the sympathetic nervous system or thyroid function. Although the food intake was not quantitated, drug therapy appeared not to have an anorexient effect. The exact mechanism of actions of these drugs cannot be ascertained from this study. Whether these drugs affect lipolysis remains to be studied. These drugs decreased serum cholesterol and at the same time increased the levels of HDL cholesterol. Further studies with the individual drug components are warranted.
3 13
1
_ 2
Significant relative to Group III: *P < 0.01.
- 8.4 2 1.6*
-9.1
f 2.1*
-9.1
- 8.2 f 2.4*
f 1.8*
-7.9 -t 2.6* - 4.0 -e 1.0*
- a.2 2 2.4* - 4.6 + 0.8*
Change in body weight (kg) Change in skin-fold thickness (mm) Change in waist circumference (cm) Change in hip circumference (em)
Group II
OF TREATMENT
4 12
-
1 1 2
Group II
Group I
AFTER COMPLETION
Group I
Description
Figures are mean f S.D.
TRIAL
Number of Patients
FAILING TO COMPLETE
CHANGES IN PHYSICAL PARAMETERS
TABLE 5
Total dropouts Patients successfully completing trial
Lack of response Side effects Incomplete investigation Personal reasons
Reasons
REASONS FOR PATIENTS
TABLE 4
- 5.7 f 2.0
- 4.2 f 2.0
-2.4 f 2.0 - 1.0 + 0.8
Group III
12 10
2
4 3 3
Group III
1
1
1
e 1.8* - 8.4 f 1.8*
-8.4
- 8.0 f 2.0* - 4.2 + 0.8*
Group IV
3 13
-
Group IV
a
+5.1 f 1.6*
+6.1 f 1.4*
Significant relative to Group III: *P < 0.05; **P < 0.01.
- 8.1 f 2.4*
- 9.8 f 1.6**
+ 1.2*
-8.2
- 10.6 f 2.4**
Change in serum cholesterol (mg%) Change in serum triglycerides (mg%) Change in HDL cholesterol (mg%)
OF TREATMENT
Group II
AFTER COMPLETION
Group I
PARAMETERS
Description
Figures are mean f S.D.
CHANGES IN BIOCHEMICAL
TABLE 6
-
to
-..__...___ ~..___
+ 5.2 + 1.4* +2.1 k 1.4
-c 1.6*
+ 2.1* -7.1
-8.1 - 5.4 f 3.8 - 2.4 f 1.2
Group IV
Group III
10
The common drug used in these treatments is Triphala guggul. This is a traditional formulation consisting of “Triphala”, a famous mixture of three myrobalans (Terminalia belerica, Terminalia chebula and Embelica officinalis) along with guggul (Commiphora mukul). “Triphala” has high claims in Ayurvedic practice and is in wide use; however, its role as an antiobesity drug remains obscure. Commiphora mukul seems to be the common ingredient in most of the antiobesity drugs described by Ayurveda. Guggul has been extensively studied for its chemistry (Khanna et al., 1969; Patil et al., 19721, pharmacology (Malhotra and Ahuja, 1972) and clinical efficacy (Malhotra and Ahuja, 1971). A number of stereoidal compounds has been isolated which have antiinflammatory capacity (Arora et al., 1971.1972). Fraction A isolated from guggul was also shown to have antihyperlipidemic activity (Mehta et al., 1968; Das et al., 1973; Nityanand et al., 1973). Although a definite hypothesis could not be drawn as to the nature of the mechanism of action of these drugs, a definite first step has been taken in the documentation of the ancient concepts of Ayurveda using modern parameters. Acknowledgements
We thank Dr. P.H. Kulkarni, Chairman, Ayurved Rasashala, sponsoring this project. Co-operation from the management Hospital is also gratefully acknowledged.
Pune, for of Nanal
References Annan, W. and Isherwood, D.M. (19691 An automated method for the direct determination serum cholesterol. Journal of Medical and Laboratory Technology 26,202211.
of total
Arora, R.B, Kapoor, V., Gupta, S.K. and Sharma, R.C. (1971) Isolation of crystalline steroidal compound from Commiphora mukul and its antiinflammatory activity. Indian Journal of Experimental Biology 9,403- 405. Arora, R.B., Taneja, V., Sharma, R.C. and Gupta, S.K. (1972) Antiinflammatory studies on a crystalline steroid isolated from Commiphora mukul. Indian Journal of Medical Research 60,929- 931. Charak Samhita (1949) Translated by Shree Gulabkunverba Ayurvedic Society, Jamnagar, India, p. 52. Chiamori, N. and Henry, R.J. (1959) Study of ferric chloride method for determination of total cholesterol and cholesterol esters. Ametican Jownal of Clinial Pathology 31,305-308. Das, D., Sharma, R.C. and Arora, R.B. (1973) Antihyperlipidaemic activity of fraction A of Commiphora mukul in monkeys. Indian Journal of Pharmacology 5,283 - 285. Galloway, S.Mc., Farquharst, D.C. and Munro, J.F. (19841 Current status of antiobesity drugs. Postgraduate Medical Journal 60 (Suppl. 3) 19-26. Khanna, D.S., Agarwal, D.P., Gupta, S.K. and Arora, R.B. (1969) A biochemical approach to antiatherosclerotic action of Commiphora mukul. Indian Journal of Medical Research 57,900 - 906. Kyle, L.H., Ball, M.F. and Doolan, P.D. (19661 Effect of thyroid hormone on body composition in myxedema and obesity. New England Journal of Medicine 275,1217. Malhotra, S.C. and Ahuja, M.M.S. (1971) Comparative hypolipidaemic effectiveness of gum guggul fraction A, ethyl-p-chlorophenoxyisobutyrate and Ciba 13437~Su. Indian Journal of Medical Research 59, 1621- 1632.
11
Malhotra, S.C. and Ahuja, M.M.S. (19721 Effect of steroidal compound isolated from fraction A of Commipkora mukul on hepatie and aortic lipid content in rats fed on atherogenie diet. Indian Jownal of ~ha~acolog~ 4,110- 113. Mehta, V.L., Malhotra. C.L. and Kalrah, N.S. (19681The effect of various fractions of gum guggul on experimentally produced hypercholesteraemia in chicks. Indian Journal of Physiology and Pharmacology 12,91- 94. Nityanand, S., Kapoor, N.K. and Dev, S. 09731 Cholesterol lowering activity of various fractions of Commiphora mukul (guggull. Indian Journal of Pharmacology 5,259 - 262. Patil, V.D., Nayak, U.R. and Dev, S. (19721 Chemistry of Ayurvedie crude drugs. I: Guggul (resin from Commiphoro mukud). I: Steroidal constituents. Tet~hedron 28, 2341- 2352. Sha~ngdha~ Samhita (1984) Translated by K.K. Shrikanta Murthi, Chaukhamba Orientia, Varanasi, India, p. 82 - 85. Silverstone, J.T. and Soloman, T. (19651The long term management of obesity in general practice. British Journal of Clinical Practice 19,395- 398. Stunkard, A.J., Caraiohead, L.W. and O’Brien, R. (19801Controlled trial of behaviour therapy, pharmacotherapy and their contribution in the treatment of obesity. Lance t 2,1045- 1047. Van Handel, E., Zilversmit, D.B. and Bowman, K. 09571 Micromethod for the direct determination of serum triglycerides. Journal of Laboratory and Clinical Medicine 50,152- 157.
AYURVEDIC TREATMENT OF OBESITY: DOUBLE-BLIND, PLACEBO-CONTROLLED
PRAKASH
PARANJPEb,
PRALHAD
PATKI’
A RANDOMISED CLINICAL TRIAL
and BHUSHAN
PATWARDHAN”
“Interdisciplinary School of Ayurvedic Medicine, University of Poona, Pune 411-007, bObesity Clinic, Nanal Hospital, Pune 411-004 and ‘Byramjee Jeejeebhoy Medical College, Pune 411-001 (Indial (Accepted October 16.1989)
Summary
Seventy obese subjects were randomised into four groups. Ayurvedic drug treatments were given for three months while one group received a placebo. Physical, clinical and pathological investigations were carried out at regular intervals. A significant weight loss was observed in drug therapy groups when compared with the placebo. Body measurements such as skin fold thickness and hip and waist circumferences were significantly decreased. Decreases in serum cholesterol and triglyceride levels were observed. No side effects of any kind were observed during the treatment period.
Introduction
Obesity is an important disorder associated with a number of potentially fatal diseases such as adult-onset diabetes mellitus and ischemic heart disease. Treating obesity has become a problem since safe drugs are not available for long-term therapy. Amphetamines have a well-defined abuse potential and drugs like diethylpropion and fenfluramine cause appreciable undesirable sympathomimetic side effects, pulmonary hypertension and depression (Galloway et al., 1984). Thyroid hormones were once used to treat obesity but are now contraindicated due to their untoward systemic effects (Kyle et al., 1966). There is a clear need for a safer drug for long-term therapy of obesity (Stunkard et al., 1980). The development of a non-toxic compound with a capacity to hold weight gain in check is much needed. Ayurveda is the ancient science of life. In the Sanskrit language, “Ayu” means life and “Veda” means the knowledge. This branch of medicine has a 5000-year record of use in the Indian system of medicine. The concepts and Correspondence
to: B. Patwardhan.
0378-8741/$04.20 0 1990 Elsevier Published and Printed in Ireland
Scientific Publishers
Ireland Ltd.
2
treatment of most of the diseases have been described beautifully and in great depth. Ayurvedic classics such as the Charak Samhita and Sushrut Samhita are still followed critically by Ayurvedic physicians in India. Obesity is referred to as “Medoroga” and is considered to be a disease of “Medadhatu” meaning a disorder of lipid metabolism. A variety of different types have been detailed in the Ayurvedic classics along with the treatment for the same. The basic concepts of obesity according to Ayurveda would be a separate topic by itself and hence will not be discussed here (Charak Samhita, 19491. The indigenous drugs described by Ayurveda are comparatively safe and have been used for many years. Drugs such as Triphala guggul, Sinhnad guggul, Gokshuradi guggul and Chandraprabha vati are claimed to be effective in the treatment of obesity (Sharangdhar Samhita, 19841 but their effectiveness has not been tested in controlled clinical trials. Therefore, we undertook a randomized, double-blind, placebo-controlled clinical trial of these agents in the treatment of obesity. Materials and methods A yurvedic medicines Composition of the four formulations are detailed in Table 1 and were obtained from the well-established company of Ayurved Rasashala of Pune which has a valid drug license issued by the Government. The authenticity of each plant and mineral component was established by the Quality Control Laboratory of the company, is also certified by the Government. All tests of identification were carried out by a qualified chemist approved by the Food and Drug Administration. Clinical studies Seventy subjects referred to the obesity clinic were entered into the trial. All were at least 20% in excess of their ideal body weight as defined by the Life Insurance Corporation of India’s height and weight recommendations. At the time of entry into the study, they had a stable weight and none was receiving any drug to reduce their weight. All were in good health and biochemically euthyroid and non-diabetic. None of them had any endocrine disorders. Their characteristics of entry are recorded in Tables 2 and 3. Serum cholesterol was determined using the method of Annan and Isherwood (19691. HDL cholesterol and serum triglycerides were determined by the methods of Chiamori and Henry (19591 and Van Handel et al. (19571. Individuals were divided randomly into four groups, namely Group I to Group IV. Treatment was planned according to Ayurvedic concepts and Triphala guggul was given to all patients in all groups except the placebo group (Group III). Other drugs given were Gokshuradi guggul (Group 11, Sinhanad guggul (Group II) and Chandraprabha vati (Group IV). Individuals in Group III received a 250-mg placebo tablet indistinguishable from the other formulations (Table 1). The subjects were interviewed individually with respect to diet and exercise
3 TABLE
1
COMPOSITION Local name
OF THE AYURVEDIC
FORMULATIONS
Scientific name
Triphala guggul ISharangdhar SamhitaI (250 mg tablet, three times a day, with lukewarm water before meals) Terminalia chebula Retz. Hirda (Combretaceael Terminalia belerica Roxb. Beheda Amalaki Pippali Guggul
(Combretaceael Emblica officinalis Gaertn. (Euphorbiaceael Piper longum Linn. (Piperaceael Commiphora mukul Hook ex Stocks (Burseraceael
Gokshuradi guggul (Sharangdhar SamhitcLI (250 mg tablet, three times a day, with lukewarm water, before meals) Tm’bulus terrestris Linn. Gokharu (Zygophyllaceael Commiphora mukul Guggul Hook ex Stocks (Burseraceael Shunth Zingiber officinale Roscoe (Zingiberaceael Piper nigrum Linn. Mire (Piperaceael Pippali Piper longum Linn. Hirda Beheda Amalaki Nagarmotha
(Piperaceael Terminalia chebula Retz. (Combretaceael Terminalia belerica Roxb. (Combretaceael Emblica officinalis Gaerth. (Euphorbiaceael Cyperus rotundus Linn. Excipients
AND PLACEBO Plant parts
Weight per tablet (mgl
Dried fruit
28
Dried fruit
28
Dried Fruit
28
Dried unripe fruit Gum oleoresin
28
Dried fruit Gum oleoresin
138
170 35
Root
5
Dried unripe fruit Dried unripe
5 5
fruit Dried fruit
5
Dried fruit
5
Dried fruit
5
Rizome
5 10
Dried fruit
10
Dried fruit
10
Dried fruit
10
(Mineral) Seed oil
15 40
Sinhanad guggul (Bhaishaj Ratnawalil (100 mg tablet, three times a day, with lukewarm water, before meals) Hirda Terminalia chebula Retz. Kombretaceael Terminalia belerica Beheda Roxb. (Combretaceael Em blica officinalis Amalaki Gaertn. (Euphorbiaceael Gandhak Sulphur, purified Ricinus communis Erandsneha Linn. (Euphorbiaceael
4 TABLE
1 (continued)
Local name
Scientific
Guggul
Commiphora mukul Hook ex Stocks
name
Plant
parts
Gum oleoresin
Weight per tablet (mgl
15
(Burseraceael Chandraprabhavati Kharangdhar Samhital (250 mg tablet, three times a day, with lukewarm Vavding Shunth Mire Pippali Pippalmool Vekhand Deodar Gajapippali Ativisha Nagarmotha Hirda Beheda Amalaki Chavak Chitrak Kachora Kadechirait Halad Saindhav Padelon Jawkhar Bidlon
water,
before meals) Embeliar ribes Burm. (Myrsinaceael Z&giber officinale Roscoe (Zingiberaceael Piper nigrum Linn. (Piperaceael Piper longum Linn. (Piperaceael Piper longum Linn. (Piperaceael Acorus calamus Linn. (Araceael Cedrus deodara Roxb., Loud. (Pinaceael Scindapsus officinalis Schott. (Araceael Aconitum he teroph yllum. Wall. (Ranunculaceael Cyper-us rotundus Linn. (Cyperaceael Terminalia chebula Retz. (Combretaceael Terminalia belerica Roxb. (Combretaceael Emblica officinalis Gaertn. (Euphorbiaceael Piper officinarum Cas D.C. (Piperaceael Plumbago teylanica Linn. (Plumbaginaceael Curcuma zedoria Rose. (Zingiberaceael Swertia chirata Buch Ham. (Gentianaceael Curcuma longa Linn. (Zingiberaceael Rocksalt, sodium chloride Sodium sulphate Impure carbonate of potash, potassium carbonate Black salt, sodium chloride
Dried
fruit
1.8
Rizome
1.8
Dried unripe fruit Dried unripe fruit Root
1.8
Rizome
1.8
Stem
1.8
Dried
fruit
1.8 1.8
1.8
Rizome
1.8
Rizome
1.8
Dried
fruit
1.8
Dried
fruit
1.8
Dried
fruit
1.8
Stem
1.8
Root
1.8
Rizome
1.8
Stem
1.8
Rizome
1.8
(Salt) (Salt) (Salt)
1.8 1.8 1.8
(Salt)
1.8
5 TABLE 1 (continued) Local name
Gulvel Daruhalad Dhane Sajjikshar Dalchini Elaichi Tamalpatra Nishottar
Plant parts
Tinospora
Stem
1.8
Rizome
1.8
Dried fruit
1.8
(Salt)
1.8
Stem skin
7.2
Dried fruit
7.2
Leaves
7.2
Root
7.2
Root
7.2
Gum
7.2
cordifolia
(Willd.1 Mires. (Menispermaceaei Berberis aristata D.C. (Berberidaceae) Coriandrum sativum Linn. 0Jmbelliferael Impure carbonate of soda, sodium carbonate Cinnamomum ze ylunicum Blume. (Lauraceael Elettaria cardamomum Maton. (Zingiberaceae) Cinnomomum cassia Blume. (Lauraceael Operculina turpethum R.Br. (Convolvulaceael Boliospermum
Danti Vanshalochan Lohabhasma Khadisakhar Shilajit Guggul Placebo
Scientific name
montanum
Muell-Arg. (Euphorbiaceael Barn busa arundinacia Willd (Gramineael Ferrous sulphate Sucrose Asphalt Commiphora mukul Hook ex Stocks (Burseraceael Excipients
(Mineral) (Carbohydrate) (Mineral) Gum oleresin -
Weight per tablet (mgl
14.4 28.8 57.6 57.6 1.6
tablet
(250 mg tablet, three times a day, with lukewarm water, before meals) Charcoal, I.P. Lactose Excipients
(Carbon) (Carbohydrate)
125 100 25
and were advised suitably. Dietary intake was not controlled. The treatment was continued for a period of three months and patients were examined every two weeks. During these visits their body weight, skinfold thickness, body measurements such as waist and hip circumference, blood pressure, temperature, pulse rate and other clinical examinations were carried out. Subjective findings such as increased or decreased appetite, feeling of lightness, sweating, breathlessness, joint pain, etc. were individually noted. Side effects of the drugs, if any, were carefully noted down. On entry and at the end
CHARACTERISTICS
52.6 +
2.6
54.6 ?
6.2
156.6 2 12.0
142.6 2 10.6
Group II 197.0 * 20.0
186.8 f
Serum cholesterol (mg%) Triglycerides (mg%) HDL cholesterol (mg%)
ON ENTRY
30.0
Group I
Description
5.2 2.7 6.0 2.8 3.0 8
88.0 + 4
16 2110 71.2 + 16.8 ? 87.6 2 100.0 + 86.6 2 128.0 “_
Group II
4.5 3.4 6.4 2.4 3.2 4
90.0 2 2
119 76.8 f 19.6 f 91.3 f 104.0 f 84.2 ? 138.0 “_
22
Group III
listed.
50.4 +
160.6 ?
2.4
6.4
188.8 ? 32.0
Group III
were noted between the four groups for the three determinations
OF THE SUBJECTS
86.0 + 2
Figures are mean + S.D. No significant differences
BIOCHEMICAL
TABLE 3
(mmHg)
Pulse rate (per minute) Systolic blood pressure (mmHg) Diastolic blood pressure
6.2 1.6 4.6 3.6
82.4 f 2.4 140.0 2 6
16 2111 76.6 2 18.4 ” 89.4 + 102.0 +
Number of subjects Male/female
Body weight (kg) Skin-fold thickness (mm) Waist circumference (cm) Hip circumference (cm)
Group I
Description
ON ENTRY
were noted between the four groups for the parameters
OF THE SUBJECTS
SD. No significant differences
CHARACTERISTICS
Figures are mean f
CLINICAL
TABLE 2
listed.
51.8 2
150.6 -t
190.6 f
Group IV
7.4
7.6
30.0
90.0 % 2
16 l/12 68.2 rt_ 4.6 20.8 f 4.1 86.4 ? 7.1 105.0 f 2.6 80.2 f 6.0 136.0 2 4
Group IV
of the study, biochemical investigations such as haemogram, tions, serum lipoproteins and cholesterol were estimated. The results were analysed by Student’s t-test.
urine examina-
Results Forty-eight subjects completed the study and there were 22 dropouts during the course of study. The dropouts were mainly from the placebo group who felt that they were not getting any benefit from the therapy. Ten subjects from the active drug groups dropped out due to a variety of reasons, including domestic and family problems (Table 4). A significant weight loss was seen in Groups I, II and IV compared to the placebo group. However, weight losses among I, II and IV were not significantly different from each other (Table 51. None of the patients in the study reported loss of appetite. Skin fold thickness and circumference of the hips and the waistline were significantly decreased as compared to the placebo group P< 0.011. There was a remarkable reduction in serum cholesterol and triglyceride levels in subjects receiving the medicaments as compared to placebo (Table 61. Subjective improvements, such as feelings of well being and lightness and decreased joint pain, appeared to be associated with the non-placebo but could not be statistically documented as significant. Minor side effects like mild diarrhoea and nausea were observed (8 in the drug therapy groups and 2 in the placebo group) but did not necessitate withdrawal of drug therapy. Discussion Obese patients are notorious defaulters (Silverstone and Soloman, 19651. In the present study, efforts were made to retain the interest and co-operation of those taking part in the study and therefore very few defaulted. In the present study, Ayurvedic drugs were given to an unselected group of obese objects. All three Ayurvedic treatments resulted in significant losses of weight relative to the placebo. It appears that treatment with these drugs can produce a clinically significant weight reduction. The reduction in skin fold thickness and hip and waist circumferences were significantly greater in drugtreated individuals as compared to placebo. The treatment did not produce any significant changes in the pulse rate, body temperature and systolic/diastolic blood pressures, indicating that these drugs do not affect the sympathetic nervous system or thyroid function. Although the food intake was not quantitated, drug therapy appeared not to have an anorexient effect. The exact mechanism of actions of these drugs cannot be ascertained from this study. Whether these drugs affect lipolysis remains to be studied. These drugs decreased serum cholesterol and at the same time increased the levels of HDL cholesterol. Further studies with the individual drug components are warranted.
3 13
1
_ 2
Significant relative to Group III: *P < 0.01.
- 8.4 2 1.6*
-9.1
f 2.1*
-9.1
- 8.2 f 2.4*
f 1.8*
-7.9 -t 2.6* - 4.0 -e 1.0*
- a.2 2 2.4* - 4.6 + 0.8*
Change in body weight (kg) Change in skin-fold thickness (mm) Change in waist circumference (cm) Change in hip circumference (em)
Group II
OF TREATMENT
4 12
-
1 1 2
Group II
Group I
AFTER COMPLETION
Group I
Description
Figures are mean f S.D.
TRIAL
Number of Patients
FAILING TO COMPLETE
CHANGES IN PHYSICAL PARAMETERS
TABLE 5
Total dropouts Patients successfully completing trial
Lack of response Side effects Incomplete investigation Personal reasons
Reasons
REASONS FOR PATIENTS
TABLE 4
- 5.7 f 2.0
- 4.2 f 2.0
-2.4 f 2.0 - 1.0 + 0.8
Group III
12 10
2
4 3 3
Group III
1
1
1
e 1.8* - 8.4 f 1.8*
-8.4
- 8.0 f 2.0* - 4.2 + 0.8*
Group IV
3 13
-
Group IV
a
+5.1 f 1.6*
+6.1 f 1.4*
Significant relative to Group III: *P < 0.05; **P < 0.01.
- 8.1 f 2.4*
- 9.8 f 1.6**
+ 1.2*
-8.2
- 10.6 f 2.4**
Change in serum cholesterol (mg%) Change in serum triglycerides (mg%) Change in HDL cholesterol (mg%)
OF TREATMENT
Group II
AFTER COMPLETION
Group I
PARAMETERS
Description
Figures are mean f S.D.
CHANGES IN BIOCHEMICAL
TABLE 6
-
to
-..__...___ ~..___
+ 5.2 + 1.4* +2.1 k 1.4
-c 1.6*
+ 2.1* -7.1
-8.1 - 5.4 f 3.8 - 2.4 f 1.2
Group IV
Group III
10
The common drug used in these treatments is Triphala guggul. This is a traditional formulation consisting of “Triphala”, a famous mixture of three myrobalans (Terminalia belerica, Terminalia chebula and Embelica officinalis) along with guggul (Commiphora mukul). “Triphala” has high claims in Ayurvedic practice and is in wide use; however, its role as an antiobesity drug remains obscure. Commiphora mukul seems to be the common ingredient in most of the antiobesity drugs described by Ayurveda. Guggul has been extensively studied for its chemistry (Khanna et al., 1969; Patil et al., 19721, pharmacology (Malhotra and Ahuja, 1972) and clinical efficacy (Malhotra and Ahuja, 1971). A number of stereoidal compounds has been isolated which have antiinflammatory capacity (Arora et al., 1971.1972). Fraction A isolated from guggul was also shown to have antihyperlipidemic activity (Mehta et al., 1968; Das et al., 1973; Nityanand et al., 1973). Although a definite hypothesis could not be drawn as to the nature of the mechanism of action of these drugs, a definite first step has been taken in the documentation of the ancient concepts of Ayurveda using modern parameters. Acknowledgements
We thank Dr. P.H. Kulkarni, Chairman, Ayurved Rasashala, sponsoring this project. Co-operation from the management Hospital is also gratefully acknowledged.
Pune, for of Nanal
References Annan, W. and Isherwood, D.M. (19691 An automated method for the direct determination serum cholesterol. Journal of Medical and Laboratory Technology 26,202211.
of total
Arora, R.B, Kapoor, V., Gupta, S.K. and Sharma, R.C. (1971) Isolation of crystalline steroidal compound from Commiphora mukul and its antiinflammatory activity. Indian Journal of Experimental Biology 9,403- 405. Arora, R.B., Taneja, V., Sharma, R.C. and Gupta, S.K. (1972) Antiinflammatory studies on a crystalline steroid isolated from Commiphora mukul. Indian Journal of Medical Research 60,929- 931. Charak Samhita (1949) Translated by Shree Gulabkunverba Ayurvedic Society, Jamnagar, India, p. 52. Chiamori, N. and Henry, R.J. (1959) Study of ferric chloride method for determination of total cholesterol and cholesterol esters. Ametican Jownal of Clinial Pathology 31,305-308. Das, D., Sharma, R.C. and Arora, R.B. (1973) Antihyperlipidaemic activity of fraction A of Commiphora mukul in monkeys. Indian Journal of Pharmacology 5,283 - 285. Galloway, S.Mc., Farquharst, D.C. and Munro, J.F. (19841 Current status of antiobesity drugs. Postgraduate Medical Journal 60 (Suppl. 3) 19-26. Khanna, D.S., Agarwal, D.P., Gupta, S.K. and Arora, R.B. (1969) A biochemical approach to antiatherosclerotic action of Commiphora mukul. Indian Journal of Medical Research 57,900 - 906. Kyle, L.H., Ball, M.F. and Doolan, P.D. (19661 Effect of thyroid hormone on body composition in myxedema and obesity. New England Journal of Medicine 275,1217. Malhotra, S.C. and Ahuja, M.M.S. (1971) Comparative hypolipidaemic effectiveness of gum guggul fraction A, ethyl-p-chlorophenoxyisobutyrate and Ciba 13437~Su. Indian Journal of Medical Research 59, 1621- 1632.
11
Malhotra, S.C. and Ahuja, M.M.S. (19721 Effect of steroidal compound isolated from fraction A of Commipkora mukul on hepatie and aortic lipid content in rats fed on atherogenie diet. Indian Jownal of ~ha~acolog~ 4,110- 113. Mehta, V.L., Malhotra. C.L. and Kalrah, N.S. (19681The effect of various fractions of gum guggul on experimentally produced hypercholesteraemia in chicks. Indian Journal of Physiology and Pharmacology 12,91- 94. Nityanand, S., Kapoor, N.K. and Dev, S. 09731 Cholesterol lowering activity of various fractions of Commiphora mukul (guggull. Indian Journal of Pharmacology 5,259 - 262. Patil, V.D., Nayak, U.R. and Dev, S. (19721 Chemistry of Ayurvedie crude drugs. I: Guggul (resin from Commiphoro mukud). I: Steroidal constituents. Tet~hedron 28, 2341- 2352. Sha~ngdha~ Samhita (1984) Translated by K.K. Shrikanta Murthi, Chaukhamba Orientia, Varanasi, India, p. 82 - 85. Silverstone, J.T. and Soloman, T. (19651The long term management of obesity in general practice. British Journal of Clinical Practice 19,395- 398. Stunkard, A.J., Caraiohead, L.W. and O’Brien, R. (19801Controlled trial of behaviour therapy, pharmacotherapy and their contribution in the treatment of obesity. Lance t 2,1045- 1047. Van Handel, E., Zilversmit, D.B. and Bowman, K. 09571 Micromethod for the direct determination of serum triglycerides. Journal of Laboratory and Clinical Medicine 50,152- 157.
