| INTRODUCTION
Xuezhikang, a new lipid-regulating medicine made up of natural substances,
is developed by WBL Peking University Biotech Co. Ltd. Many researches
on the pharmacology and toxicology [1,2] as well as clinical effects
and safety of this medicine have been carried out at home and abroad
in the past years. [3,4] Reports on lipid lowering effect of Gemfibrozil
(Nuoheng as the trade name in China, manufactured by Zhuzhou Xiangjiang
Pharmaceutical Company in Hunan Province) appeared in both China
and foreign countries.[5] In this study, Xuezhikang and Gemfibrozil
were employed to compare clinical observations of lipid reduction
between aged primary hyperlipoidemia and non-insulin dependent diabetic
patients (NIDDM). It is described as the followings.
INFORMATION AND METHOD
Patients
Older
hyperlipoidemia patients with serum TC > 5.7 mmol/L and/or TG
> 1.7 ~ 4.5 mmol/L and HDL-C > 1.0 mmol/L were chosen as target
patients totaling 86. They were classified as:
- 52
primary hyperlipoidemia patients aging at 63 ± 3 years
old and BMI 25.8 ± 2.8, 40 male and 12 female, with 49
cases of high TC, 41 cases of high TG and 33 cases of low HDL-C.
Among them, 30 cases were associated with coronary heart disease,
15 cases with hypertension and 8 cases with cerebral infarction.
They were randomly divided into the Xuezhikang treatment group
and the Gemfibrozil treatment group with 26 cases in each group
- 34
cases of NIDDM with slight to moderate diabetes treated with sugar
regulating drugs, aging at 60 ± 4 years old and BMI 27.0
± 2.8, 25 male and 9 female, with 31 cases of high TC,
27 cases of high TG and 19 cases of low HDL-C. Among them, 20
with hypertension, 17 with coronary heart disease and 5 with cerebral
infarction. They were classified into the Xuezhikang treatment
group and the Gemfibrozil treatment group with 17 cases in each
group. Every patient should not take any medicine such as lipid
lowering drug, phenthazine, b receptor inhibitor and sexual hormone
at least for 1 month while keeping their diet and exercise habit
unchanged.
Methods
Patients in Xuezhikang group took two capsules a time (containing
0.3 g Xuezhikang), twice a day. And those in Gemfibrozil group took
0.6 g Gemfibrozil twice a day for 4 weeks as one treatment. FBG,
insulin, functions of liver and kidney, regular blood and urine
testing items, lipid level and side-effects before and after the
treatment were checked and recorded.
Criteria for Effects
It was identified according to Guiding Principles
on Clinical Study of Lipid Reduction Medicines stipulated by Ministry
of Public Health.
Highly
effective: TC decrease ³ 20% or TG decrease ³ 40%, or
LDL-C decrease ³ 20%; HDL-C increase ³ 20%;
Effective: TC decrease by 10% ~ 19%, TG decrease by 20% ~ 39%, LDL-C
decrease 10% ~ 19%; HDL-C increase 10%~19%;
Ineffective: not reaching the above standards;
Deterioration: TC increase ³ 10%, TG increase ³ 10%, LDL-C
increase ³ 10%, HDL-C decrease ³ 10%.
Statistical
Methods
Data
of each group were analyzed by t-test, whereas individual curative
effect analysis was processed by x2 test.
RESULTS
Lipid Levels before and after the
Treatment
Blood
lipid changes of the two groups drive to the same direction with
different range. And they were not statistically significant. (See
Table I)
| Table
I. Lipid Level Change Treated by Xuezhikang and Gemfibrozil |
|
Group
|
Primary
Hyperlipoidemia(26 cases)
|
NIDDM(17
cases)
|
|
|
Before
treatment
|
After
treatment
|
Change(%)
|
Before
treatment
|
After
treatment
|
Change(%)
|
|
Xuezhikang
Group
|
| TC(mmol/L) |
6.90±1.30
|
5.12±1.13b
|
-25.96
|
6.35±1.23
|
5.07±1.06b
|
-20.36
|
| TG(mmol/L) |
2.97±1.16
|
2.14±0.93b
|
-24.67
|
3.86±1.75
|
2.42±1.00b
|
-28.81
|
| HDL-C(mmol/L) |
0.94±0.19
|
1.02±0.93a
|
13.8
|
0.92±0.18
|
1.13±0.16a
|
13.47
|
| LDL-C(mmol/L) |
4.96±1.35
|
2.95±1.26b
|
-38.44
|
4.70±0.92
|
3.01±0.62b
|
-36.75
|
| APOA(g/L) |
1.27±0.20
|
1.40±0.23a
|
8.3
|
1.25±0.18
|
1.37±0.21b
|
10
|
| APOB(g/L) |
1.59±0.46
|
1.27±0.34b
|
-20.8
|
1.57±0.32
|
1.18±0.33b
|
-24
|
|
Gemfibrozil
Group
|
| TC(mmol/L) |
6.69±0.97
|
4.96±0.85b
|
-23.57
|
6.81±1.02
|
5.22±0.95b
|
-22.32
|
| TG(mmol/L) |
3.15±1.18
|
1.75±0.60b
|
-45.26
|
3.76±1.34
|
1.97±0.90b
|
-46.12
|
| HDL-C(mmol/L) |
0.93±0.21
|
1.26±0.23a
|
21.9
|
0.89±0.21
|
1.25±0.23b
|
22.3
|
| LDL-C(mmol/L) |
4.85±1.24
|
3.50±1.07a
|
-25.25
|
4.78±1.12
|
3.24±0.99a
|
26.97
|
| APOA(g/L) |
1.25±0.20
|
1.33±0.21a
|
10
|
1.19±0.17
|
1.29±0.20a
|
11
|
| APOB(g/L) |
1.60±0.46
|
1.18±0.34b
|
-24
|
1.56±0.31
|
1.20±0.35b
|
-25
|
Individual
Effect
Individual
effect comparison on lipid reduction by Xuezhikang and Gemfibrozil
is shown in Table II.
| Table
II. Individual Effect Comparison 4 Weeks after Treatment |
|
Index
|
Primary
Hyperlipoidemia
|
|
|
Cases
|
Highly
effective
|
Effective
|
Ineffective
|
Deterioration
|
Total
efficacy (%)
|
|
Xuezhikang
Group
|
| TC |
24
|
21(87.5)
|
2
(8.3)
|
1
(4.2)
|
|
23
(95.8)
|
| TG |
21
|
11(53.4)
|
4
(14.9)
|
5 (23.8)
|
1
(4.8)
|
15
(72.4)
|
| HDL-C |
16
|
5(31.3)
|
6
(37.5)
|
5
(31.3)
|
|
11
(68.8)
|
|
Gemfibrozil
Group
|
| TC |
25
|
12
(44.4)
|
7
(28.0)
|
6
(27.6)
|
|
20
(72.4)
|
| TG |
20
|
16
(82.0)
|
4
(18.0)
|
|
|
20
(100)
|
| HDL-C |
17
|
9
(82.9)
|
6
(35.3)
|
2
(11.8)
|
|
15
(88.2)
|
|
Index
|
NIDDM
|
|
|
Cases
|
Highly
effective
|
Effective
|
Ineffective
|
Deterioration
|
Total
efficacy (%)
|
|
Xuezhikang
Group
|
| TC |
16
|
14
(88.0)
|
1
(6.0)
|
1
(6.0)
|
|
15
(94.0)
|
| TG |
13
|
15
(72.4)
|
3
(23.1)
|
3
(23.1)
|
|
10
(76.4)
|
| HDL-C |
9
|
3
(33.3)
|
4
(44.4)
|
2
(22.3)
|
|
7
(77.7)
|
|
Gemfibrozil
Group
|
| TC |
15
|
6(40.0)
|
4
(26.7)
|
5
(33.3)
|
|
10
(66.7)
|
| TG |
14
|
11(78.6)
|
2
(14.3)
|
1
(7.1)
|
|
13
(92.4)
|
| HDL-C |
10
|
6(60.0)
|
2
(20.0)
|
2
(20.0)
|
|
8
(80.0)
|
Follow-up Effects
4
weeks after treatment, 20 of the 34 NIDDM patients were randomly
selected and tested with their lipid level. It was found that their
lipid level elevated in average close to that before treatment when
they ceased administrating lipid-lowering agents for 4 weeks. Then
they were fed with Xuezhikang for another 4 weeks and their lipid
level decreased (see Table III).
| Table
III. Post Treatment Investigations of Lipid Level of 20 NIDDM
Patients (mmol/L) |
|
Stop
treatment for 4 weeks
|
4-week
Treatment again
|
Change(%)
|
| TC |
6.72±1.13
|
5.16±1.13b
|
-23.52
|
| TG |
3.89±1.90
|
2.71±0.92b
|
-25.84
|
| HDL-C |
0.89±0.16
|
1.15±0.59a
|
12.18
|
| LDL-C |
4.72±0.83
|
3.28±0.71b
|
-27.56
|
| a:P<0.05;
b:P<0.01 |
The Change of Insulin Sensitivity Index before and after the Treatment
| Table
IIII. The Change of Insulin Sensitivity Index |
|
Before
treatment
|
After
treatment
|
|
Primary
Hyperlipoidemia
|
| Xuezhikang
group |
14.60±3.21
|
15.10±3.40
|
| Gemfibrozil
group |
14.32±3.82
|
14.80±4.10
|
|
NIDDM
|
| Xuezhikang
group |
14.62±4.00
|
15.40±4.60
|
| Gemfibrozil
group |
13.98±3.90
|
15.20±5.00
|
| Insulin
sensitivity index is 10-3 mU/ml·mmol/L |
Side-effects
There
were 4 patients (9.5%) in Xuezhikang group feeling discomfort in
their mid-upper stomach which had been alleviated automatically
1 weeks later. Meanwhile, 1 case (2.4%) in Gemfibrozil group had
diarrhea and the symptom disappears as soon as the medicine is taken
after dinner. Liver and kidney functions, routine blood and urine
test items as well as platelet level of every patient in the two
groups fell into normal range after the treatment.
DISCUSSION
Xuezhikang is manufactured and refined from specially made Hongqu
(red yeast rice or Monascus purpureus) by high biotechnology. It
is rich in HMG-CoA reductase inhibitor. And animal experiments proved
its strong capacity in reducing serum TC, TG and (TC - HDL-C)/HDL-C
ratio of rabbit and quail models. Meanwhile, Xuezhikang inhibits
the formation of atherosclerosis plaques and lipid deposition in
liver of rabbit. [3,4] Gemfibrozil is a lipid-lowering medicine
of the nature of phenoxy aryl acid. Domestic and abroad clinical
studies have proved its remarkable effects on lipid modulation.[5]
The findings of this clinical research showed that both Xuezhikang
and Gemfibrozil performed well in decreasing serum TC, LDL-C and
APOB. And Xuezhikang achieved better results in reducing serum TC
and LDL-C than that of Gemfibrozil. Whereas Gemfibrozil performed
better than Xuezhikang in decreasing serum TG and elevating HDL-C.
The total efficacy of TC reduction by Xuezhikang in 40 hyperlipoidemia
patients in the two groups reached 94.9%, higher than that of Gemfibrozil
71.9% (P < 0.01). Also, in 34 cases of high serum TG patients,
the total efficacy of TG reduction by Gemfibrozil were 96.45%, higher
than that of Xuezhikang 74.15% (P < 0.01). The total efficacy
of Xuezhikang on elevating HDL-C in 25 cases reached 73.32% whereas
that of Gemfibrozil in 27 cases stayed at 85.1% (P > 0.05). Although
some improvement occurred on insulin sensitivity index in both Xuezhikang
group and Gemfibrozil group, no stitistic difference occurs. This
may has something to do with the improvement of glucose tolerance.
In
order to exclude the influence of improved sugar metabolism and
lipid-lowering medicine on serum lipid level, 20 stable NIDDM patients
were chosen to investigate the effect of Xuezhikang on lipid reduction
through self-control observations. The findings did indicate its
performance on improving the metabolism of lipid. Therefore, it
is concluded that regulating sugar metabolism disorder alone is
not enough for diabetes patients. Disorder of lipid metabolism should
also be controlled so as to achieve better results in preventing
the occurrence of atherosclerosis.
The
differences of lipid regulation by Xuezhikang and Gemfibrozil lies
in different treating mechanism. Xuezhikang mainly reduces the synthesis
of cholesterol, elevates the production of LDL-C receptor and facilitates
the clearance of LDL in blood through competitively suppression
of HMG-CoA functioning in the early stage of cholesterol synthesis.
[6] Whereas for Gemfibrozil, it mainly reduces serum TG by decreasing
the synthesis of VLDL-TG and activates lipoprotein lipoidase to
speed up the clearance of TG. [7] The increase of serum HDL-C results
from the increase of HDL3 synthesis in liver and the acceleration
of TG decomposition leading to the production of more HDL2.[8] Thus,
it is considered that patients with high serum TC should take Xuezhikang
and patients with high TG or low HDL-C should administrate Gemfibrozil.
REFERENCES
|
1
.
|
Zhu
yan, Li Changling, Wang Yinye. Effects of Xuezhikang on lipid
reduction of hyperlipoidemia rabbit and quail models, Chinese
Pharmaceutical Journal, 1995, 30(11):656. |
|
2.
|
Li
Changling, Li Yafang, Hou Zhonglin. Toxicity study of Xuezhikang,
Bulliton of Chinese Pharmocological Society, 1995, 12(4):12. |
|
3.
|
Wang
Junxian, Lu Zongliang, Chi Jiamin, et al. Clinical observation
of hyperlipoidemia treated by Xuezhikang, Chinese Journal of
Experimental Traditional Medical Formulae, 1995, 1(1):1. |
|
4.
|
Shen
Zhiwei, Yu Pulin, Sun Meizhen et al. Projective study on primary
hyperlipoidemia treatment by Xuezhikang, National Medical Journal
of China., 1996, 76:156. |
|
5.
|
Manninenv,
Molkonen M, Eislo A, et al. Gemfibrozil in the treatment of
hyperlipoidemia:a 5-year follow-up study. Acta Med Scand, 1982,
668(Suppl):S82. |
|
6.
|
Brolo
MS, Goldstein JL. Areceptor-mediated pathway for cholesterol
homeostasis, Science, 1986, 232:34. |
|
7.
|
Kashyap ML. Mechanism of action of gemfibrozil. Today's Therapeutic
Trends, 1985, 1(Suppl):S31 |
|
8.
|
Manninen
V. Clinical results with genfibrozil and background for the
Helsinki heart study, Am J Crdio, 1983, 52:356. |
|
