Analysis of Weight-Reducing/ reduction? Effects of Kintopill™ in Obese Rats

(Chen Yu, et al. Department of Pathophysiology, Shanghai Medical
University, Shanghai, 200032)

Objective:   To investigate the weight-reducing effect of Kintopill™ and its probable mechanism in obese rats.

Method:   The obese rats' body weight, Lee's index, total weight of celiac fat tissue, adipocyte size, blood glucose, blood lipid, expression of leptin in adipocyte (ABC method), level of surem leptin (RIA) were chosen as the indexes.

Results:  After administration of Kintopill™ (40mg/100g B.W./d.), the rats lost their body weights to some extent. At the same time, blood cholesterol and glucose levels were lowered and adipocyte's leptin expression reduced, while serum leptin levels were elevated.

Conclusions:  Kintopill™ reduces the weight of obese rats when it is administered to the rats for more than thirty days with a dosage of 40 mg/100g B. W./d.

The mechanism of its weight-reducing effect may be related to serum leptin elevation. It also lowers blood cholesterol levels. As obesity is frequently accompanied by hyperglycemia, blood glucose can be reduced to lower levels when Kintopill™ is administrated.

An Experimental Study on the Preventing Obesity by Kintopill™ in Rats
(Qu Xiaoyi, et al. Department of Pathophysiology, Shanghai Medical University, Shanghai, 200032)

Objective:   To investigate the effects of Kintopill™ in preventing obesity and its probable mechanism in obese rats.

Method:   Twenty-six newborn SD rats were randomly grouped as prevention group (n=8), control group (n=8) and normal group (n=10).  The rats in the prevention group and control group were fed with high-energy forage and those in the normal group were fed with ordinary forage. The rats in prevention group were administrated with Kintopill™ (40mg/100g B.W./d.) from 9th to 17th weeks.

Dynamic changes in body weight, celiac fat weight and adipocytes were measured. Immunnohistological analysis of leptin in celiac adipocytes (ABC method) and the measurement of serum leptin levals (RIA method) were conducted.

Results:  The body weight and net weight of celiac fat were  lower, their adipocytes were smaller and immunochemical stainings of leptin were weaker in the prevention group than that in the control group. There was an obvious positive relationship between the expression of leptin and celiac fat tissue weight
(r=0.8663, P<0.05). But the changes in serum leptin levels were not significant.

Conclusion:  Kintopill™ (40mg/100g B.W./d.) can prevent obesity in rats fed with high-enegy forage. The mechanism may be related to the decrease of adipocytes leptin expression.

Clinical and Experimental Studies of Rhubarb Extracts and Kintopill™ (A Complex Preparation of Rhubarb) for the Treatment of Obesity

I. The Origin of the Idea of Treating Obesity Using Rhubarb Alone

Obesity facilitates retention of lipophilic toxicants in the human body. Statistical analyses indicate that the lifetime of overweight subjects at the age of 45 and over is 4 years less than that of normal subjects. Moreover, being overweight brings risks of brain thrombus, coronary heat disease, high blood pressure, diabetes mellitus, cholelithiasis, and sudden death .... sudden death???

The mortality rate induced by these complications in overweight subjects is dramatically increased when compared to people with normal weight.

Furthermore, the overweight are also susceptible to breast and
enteric cancers and accelerated aging.

The Clinical Research Data of 5,000 Human Obesity Cases

(1) Diagnosis criteria

All patients were diagnosed with simple obesity.

Subjects:
10 - 19% overweight were defined as overweight (OW),
20 - 30% overweight as light obesity (LO),
31 - 50% overweight as medium obesity (MO), and
51% overweight as serious obesity (SO).

The standard body weight was calculated as the following equation:

Standard Body Weight (kg) = [Height (cm) - 100 (cm)]/0.9

(2) Patient data

Five thousand cases were studied, including 596 male and 4,404 female patients with an average age of 39 (5 to 88). The average disease course was 8.9 years, ranging from 0.2 to 60. The classification of severity of obesity were:
OW, 1,355 cases (26.7%),
LO, 1,125 cases (22.5%),
MO, 1,642 cases (32.8%), and
SO, 898 cases (18.0%).

The causes of obesity included:
improper diet (1,700 cases, 34%),
insufficient exercise (1,231 cases, 24.6%),
post - delivery, genetic susceptibility, post - operation, medications, and unknown factors.

The combined causes of improper nutritional intakes and insufficient exercise induced obesity in 59% patients. From 5,000 cases, 3150 (63%) patients were accompanied with hepatic steatosis, 700 (14%) patients with high blood pressure, 1,300 (26%) patients with hyperlipemia, 1,350 (21%) patients with high blood viscosity, 881 (17.6%) patients with menstrual imbalance, 1,600 (32%) patients with an aversion to warm temperature, 2,600 (52%) patients with polyhidrosis, 802 (16%) patients with fatigue, 600 (12%) patients with dizziness and head distention, 850 (17%) patients with short breath and/or palpitation, and 350 (7%) patients with constipation.

(3) Patient data for the comparisons between rhubarb and other medications (A) A total of 100 cases of simple obesity were randomly selected and equally divided in to two therapy groups of RRT (No. 2 Tablet for lowering Lipids) and fenfluramine (FF).

In the RRT group, 10 male and 40 female patients were recruited. The average age of patients was 46 (25 to 65) and the average disease course was 9 (3 to 15) years. The obesity classifications were: LO, 14 cases, MO, 18 cases, and SO, 18 cases. In the
FF group, 14 male and 36 female patients were recruited with an average age of 43 (24 to 64) and an average disease course of' 10 (1 to 17) years. The obesity classifications were: LO, 20 cases, MO, 17 cases, and SO, 13 cases.

The patients of both testing groups showed similar and comparable symptoms with similar complications, including an aversion to warm temperature, polyhidrosis, fatigue, dizziness, constipation and head distention, short breath and/or palpitations.

(B) The effectiveness of 50 cases treated with RRT were randomly compared with that of the other 50 cases treated with Xiao Pang Mei a Chinese proprietary medication. In the RRT group, 5 male and 45 female patients were recruited with an average age of 43 (22 to 70) and an average disease course of 8 (2 to 13) years.

The obesity classification was: LO, 32 cases, MO, 17 cases, and SO, 1 case. In the Xiao Pang Mei group, 4 male and 46 female patients were recruited with an average age of 40 (21 to 67) and an average disease course of 7 (3 to 12) years. The obesity classifications were: LO, 26 cases,  MO, 19 cases, and SO, 5 cases.

The patients of both testing groups showed similar and comparable symptoms, and were accompanied with similar complications.

(C) A total of 137 cases were tested with # 1 Tablet, while 135 cases were recruited as controls. In the group of # 1 Tablet, 91 male and 46 female patients were recruited with an average age of 12 (9 to 13) and an average disease course of 4 years. The obesity classification was: LO, 34 cases, MO, 68 cases, and SO, 35 cases. In the control group, 90 made and 45 female patients were recruited with an average age of 12 (9 to 13) and an average disease course of 4 years. The obesity classification were: LO, 33 cases, MO, 68 cases, and SO, 34 cases. All 272 patients who participated in the test were randomly selected from Shanghai Summer Campus for Overweight Children in July 1991. All candidates were physically examined, showing similar and comparable health conditions.

A Summary of Effectiveness Analyzed by Random Comparisons between Rhubarb Preparations and Controls
Δ XPM: Xiao Pang Mei
The therapy results of kintopill
(A) An effectiveness of 95% was achieved in 100 patients, who were treated with Kintopill™ for 40 days. 95% effective patients lost an average weight of 7kg and waist loss of 6.5cm.
(B) The Effectiveness of Kintopill™ - treated 33 cases conducted by a division of  the Ministry of Health. All 33 cases treated with Kintopill™ for 40 days showed the effects of weight loss and lipid lowering and significant improvement of hepatic lipid invasion. Kintopill™ had the capabilities of weight loss and lipid lowering, but without any effects of dehydration, thus, Kintopill™ did not hurt normal physiological status. The average weight loss was 4.7kg, ranging from 2.5 to 8kg, including 2.9kg body fat loss. A significant difference was achieved (p < 0.05) when compared between posterior to and prior to the Kintopill™ therapy. A significant difference was also obtained when several parameters, including the thickness of subcutaneous fats in the arms and around the umbilicus, as well as the waist size, were compared between prior to and pos terior to the Kintopill™ treatment (all p < 0.05). The effectiveness achieved by treating with Kintopill™ for 40 days were similar to that obtained by treating with RRT for 3 months (See Table 11 - 3). This fully documents that Kintopill™ is better than all the other rhubarb extracts mentioned previously.

The Comparison of Effectiveness between Kintopill™ and RRT

The principal effect of Kintopill™ was to reduce body lipids rather than water, instead, the ratio between water and body weight was slightly increased, thus, there was no dehydration induced by Kintopill™ (See Table 11 - 4).

The Determination of Physical Stamina Prior to and after the Kintopill™ Therapy [Mean ± SD (l/min)]

From 33 cases tested, seven patients showed increased blood trig ycerides (blood fat). Five patients recovered to normal after 40 days Kintopill™ treatment, with an effectiveness of 71 %. The other two patients showed decreased trigl ycerides, which were still higher than normal. Prior to the Kintopill™ therapy, al1 patients had low HDL, which returned to normal after therapy. Thus, this indicates that Kintopill™ has the ability to balance blood lipid.

From 33 cases tested, 21 patients showed various severity of hepatic lipid invasion. After 40 days' Kintopill™ treatment, the following two different kinds of results were obtained.

(a) One (10%) of the ten cases of hepatic steatosis was cured by Kintopill™ therapy and another one (10%) was improved.
(b) From 11 cases with slight hepatic lipid invasion, 3 (27%), cases were cured, while one (9%) case was improved. Thus, a total effectiveness of 56% was reached after 40 days' Kintopill™ treatment on hepatic lipid invasion and steatosis. A previous result showed only 40% effectiveness of RRT for the treatment of hepatic steatosis, indicating that the effectiveness of Kintopill™ was better than that of RRT for the treatment of hepatic steatosis.

Side Effects
(l) Low abdominal pain occurred in some patients before defecation, when they were treated with orally infused tablets of rhubarb extracts or complex preparations. This was due to colon spasm and disappeared soon after defecation. Thus, no treatment was required for this kind of abdominal pain.

(2) Among 5,000 cases treated with rhubarb preparations, only 3 cases showed allergic skin rashes, which appeared half a day after medication. Such skin rashes could be treated with anti - allergic agents, e.g. chlorpheniramine.

Conclusions and Discussion
1. The Clinical Effectiveness and Mechanism Study of Rhubarb Extracts on weight loss
(l) Similar effectiveness has been achieved by # 1 Tablet and RRT for the treatment of obesity and accompanied symptoms and diseases. However, the dosage of # 1 Tablet is less than that of RRT, approximately, the effects of 3 tablets RRT are equivalent to 2 tablets # 1 Tablet, by which side effects are more prominent.
(2) The summary of 5,000 outpatient cases documents that over 93.3% effectiveness is achieved by # 1 Tablet and RTT. A total of 5.8kg weight loss and 5.5cm waist loss are obtained after 3 months' treatment. The effects are more significant in the treatment of OW and LO. The rhubarb therapy is also effective to treat accompanied diseases, such as hypertension, hyperlipemia, and hepatic steatosis.
(3) A study on 200 randomly selected patients demonstrates that the effectiveness of RRT is similar to that of FF, a known drug for weight loss (p > 0.05), but better than that of Xiao Pang Mei, a nationwide (China) known Chinese proprietary medication (p < 0.05). The comparison between 137 cases treated with # 1 Tablet for one week and 135 control cases without treatment demonstrates a significant difference of 0.93 kg weight loss (p < 0.05). 
(4) Jin Huiming et. al. have conducted the experimental animal studies and compared the pharmacological effectiveness between various dosages of RRT and FF. The results demonstrate that the mid - dosage of RRT surpasses FF in weight loss. Physicians in TCM commonly treat the dosing methods as proprietary information. Thus, different dosages should be prescribed for individual patients during the obesity therapy.
(5) There is a difference in effectiveness between patients treated in - hospital and out patient clinics. For example, the research result of 5,000 out - patient cases has shown weight loss of 2.6 and 5.8kg and waist loss of 3.2cm and 5.6 cm, respectively after one and three months' therapy. However, the result of 300 hospitalized patients has shown weight loss of 8.3 and 19 kg and waist loss of 8.3 and 18.7cm, respectively. Therefore, the hospitalized subjects effectiveness in loss of weight and waist is approximately 3.5 times as much as outpatient effectiveness.
(6) The toxicity of # 1 Tablet and RRT have been tested by the animal experiment and clinical observation. Neither has been found to induce any toxicity. Daily defecation of 2 - 3 times pasty feces is within the physiologic range, and is not harmful to the human body. Recently, a 6 - month long - term toxicity) test and some genetic toxicity tests have also documented that these two rhubarb preparations are safe and free from toxicity.
(7) The Department of Pathphysiology, Shanghai Medical University has assisted to study the mechanism of RHT for the treatment of obesity, the results follow:
(A) There are no substantial changes of intestinal villi induced by the oral infusion of RRT, which does not affect the normal nutritional intake by the human body. But a retardation of gastric emptiness is induced by RRT and followed by a retarded hungry feeling.
(B) Orally fed RRT induces more rapid movement of enteric contents, thus, the lipid intake is reduced.
(C) In addition to weight loss, the decreased Lee's Index, reduced adipose tissue, diminished dimensions of adipocytes, lowered blood cholesterol, triglycerides and LDL have been found in rats treated with RRT, when compared to normal controls, documenting RRT induced inhibition of lipid biosynthesis. The experimental results have show an enhanced, but localized dissolution of mesentery fat, in addition to inhibition of lipid biosynthesis after medication.
(D) Variable sensitivities to RRT have been detected from adipocytes at differently locations. The highest sensitivity to RRT has been found from adipose tissues inside peritoneal cavity. This is consistent to the clinical results, which have found more prominent waist loss in patients with large bellies.
2. The Clinical Trials and Mechanism Studies of Kintopill™ on Weight Loss
Kintopill™ has been further developed and advanced based on the above - mentioned accomplishments. Kintopill™ has much better effectiveness than other rhubarb extracts.
(1) An average of 7kg weight loss with 6.5cm waist loss is achieved in 100 cases simple obesity after a 40 - days treatment course of Kintopill™. Such an effectiveness of weight loss is greatly over that induced by RRT (See above Table 11 - 3). The effectiveness obtained from hospitalized patients is approximately 2 times as much as that from outpatients.
(2) The laboratory examinations have demonstrated that Kintopill™ reduces lipids, but not water in the human body, thus, Kintopill™ dose not reduce physical strength. In the contrary, Kintopill™ increases body strength, eliminates symptoms, including constipation, an aversion to warm temperature, polyhidrosis, palpitation, and short breath.
(3) Kintopill™ is very effective for the treatment of high blood pressure, Hyperljpemia, Hyperinsulinemia, Hyperglycemia, and hepatic steatosis.
(4) The experiments conducted by Jin Hui - ming demonstrate:
(A) Kintopill™ at the moderate dosage shows the best effectiveness, especially, the most significant body weight loss and reduces Lee's Index. It is even better, if dieting is controlled.
(B) Kintopill™ is also very effective for the treatment of obesity accompanied with hyperlipemia and hyperglycemia.
(C) In addition to the effects on hyperlipemia and hyperglycemia, Kintopill™ has the capabilities of removing and expelling toxins, and protecting important organs. Jin's experiments document that Kintopill™ decreases the concentrations of endotoxin, and inhibits the production of Tumor Necrosis Factorα (TNFα), which induces cell damages when interacts with corresponding cell surface receptors.
(D) Mechanism study of Kintopill™ on weight loss
(a) Gastric Peristalsis slowed down and a retardation of gastric emptiness is induced by Kintopill™ and followed by a quick disappearance of hungry feeling, But orally fed Kintopill™ induces more rapid movement of colons, times of defecation are increased and undigested, unabsorbed lipid are eliminated.
(b) Kintopill™ reduces both the volume of adipocytes and weigh of adipose tissue.
(c) Study of cell receptor: there are an elevation of insulin receptor activity, enhancement insulin sensitivity and decrease of insulin - resistance by the oral infusin of Kintopill™. From its very source it is proven that Kintopill™ has  multi-functional mechanisms.
 (d) Study of gene expression level: leptin of adiposcyte in obese rat and expression of C/EBPαmRNA are lowered on an average after treatment by Kintopill™ the two having significant positive correlations, therefore partly inhibiting initiation of obese gene in adiposecyte.
(e) Chemical studies of Kintopill™: three pure compounds of d - catechin, gallic acid and oligosaccharide have been separated as the effective constituents for inhibited pancreatic lipase. Therefore part of the substance basis of kintopill's inhibiting the digestive and sssss

Case Studies
1. Huang Chi (male, age, 28) from Wuhan, China was admitted on 5/24/2000 (registration No. 11594) and discharged on 9/1/2001. At admission, his height was 172cm with a body weight of 209.5kg, and waist at 171cm (picture 3).

After trying several methods of weight loss, including exercise, without success,
Kintopill™ was prescribed for him.   He lost 50kg, from 209.5 to 159.5kg after 4 months' treatment with Kintopill™.

He lost 19kg during the first month therapy, then 7kg in the second month, 11.5kg in the third month, and 12.5kg in the fourth month. His waist was slimmer by 27cm, from 170 to 143cm, with increased bodily strength and prominently improved health.

In addition, the following items returned to normal or significantly improved 2 months after treatment: (1) Blood pressure dropped from 140/95 to 130/80mmHg; (2) total and direct bilirubin returned to normal; (3) insulin releasing test returned to normal; (4) myocardial ischemia was eliminated (T wave of EKG changed from flat to vertical); and (5) hepatic steatosis was improved.

After the Kintopill™ treatment, he lost a total of 125.5kg  which was 60% of his original weight. He also lost 85.5cm at his waist, which was 50% of his original waistline. All obesity-related diseases and symptoms disappeared. He walked better with much stronger bodily strength. He looked totally different from his previous self.

2 Yamakuchi (Japanese, female, age, 31) height of 167cm, weight of 73kg (this case was classified as SO, because the standard weight should be 60.3kg), body fat of 34.3%, and waist of 92cm (picture 24). After only ten days therapy, she lost 5.8kg, 2.8% of body fat, and 6.7cm at the waistline. The c1assification was changed from SO to OW.