Nursing Research 5
glovesme
htn_prunes.pdf
J Ayub Med Coll Abbottabad 2010;22(1)
http://www.ayubmed.edu.pk/JAMC/PAST/22-1/Talat.pdf 28
USE OF PRUNES AS A CONTROL OF HYPERTENSION Talat Ahmed, Halima Sadia, Sadia Batool, Ayesha Janjua, Faiza Shuja
Department of Pharmacology & Therapeutics, Shifa College of Medicine, Islamabad, Pakistan
Background: Fruits and vegetables are shown to reduce blood pressure. It is not merely the antioxidants contained in fruits and vegetables that have health benefits such as lowered systolic and diastolic blood pressures. This study was undertaken to see the cardiovascular protective effects of prunes. Methods: A placebo controlled clinical trial study was designed to see the effects of Prunus domestica on blood pressure in 259 pre-hypertensive (Systolic BP=120–139 mmHg, diastolic BP=80–89 mmHg) volunteers. Treated groups drank prune juice and ate the whole fruit (dried plums) while either 3 (about 11.5 gm) or 6 prunes were soaked overnight in a glass of water whereas control group took only a glass of plain water early in the morning on empty stomach. Blood pressure was recorded fortnightly for 8 weeks, and blood samples were taken at 0 and 8 weeks. Results: There was significant reduction of blood pressure by single dose of prunes daily group and the controls (p<0.05). With the double dose of prunes, only systolic BP was reduced significantly (p<0.05). Control group had significantly increased serum HDL whereas test groups had significantly reduced serum cholesterol and LDL (p<0.05). Data was analysed by paired-sample t-test with 95% confidence interval. Conclusion: The data predicts cardiovascular protective effects of prunes. Keywords: Plums, Prunus domestica, blood pressure, lipid profile, pre-hypertensive patients
INTRODUCTION A high concentration of fruits and vegetables has been correlated with a decrease in cardiovascular disease.1 It is interesting to note that according to various studies, it is not merely the antioxidants contained in fruits and vegetables that have health benefits such as lowered systolic and diastolic blood pressures. Trial studies have shown that vitamin supplements of these antioxidants do not produce the same results on subjects as do fresh fruits and vegetables.2
It is predicted that by the year 2020 Coronary Heart Disease (CHD) along with cerebrovascular disease will rank among the leading causes of death in the world 1st and 4th respectively.3 This is mainly due to the rapid increase of death by these causes in the developing world. The pathogenesis of CHD and stroke is intricately linked with elevated blood pressure, and thus to turn away from the dismal state of affairs predicted for the future, we must now turn to limiting the number of victims within the population as well as reducing the severity in individuals already suffering from this primarily idiopathic disease process.
Hypertension has been classified by the Joint National Committee into several subclasses. A newly categorised group of individuals have been termed as pre-hypertensives, with a systolic blood pressure of 120–139 mmHg or a diastolic blood pressure of 80–89 mmHg. These patients require health promoting lifestyle modifications in order to prevent cardiovascular disease.4 Stage 1
hypertensives are those with a systolic BP of 140– 159 mmHg or a diastolic BP of 90–99 mmHg, and stage 2 hypertensives are those individuals exhibiting readings ≥160 mmHg systolic and ≥100 mmHg diastolic.
The objectives of the study were to see if the use of prunes is useful in cardiovascular disorders to bring about changes in blood pressure or prevention of atherosclerosis, and possibility of developing new drug from organic source.
MATERIAL AND METHODS All pre-hypertensive adult patients (above the age of 18 years) coming in Shifa Foundation Community Health Centre (SFCHC) OPD were included in the study. Two hundred fifty-nine (259) pre-hypertensive patients were selected and divided into A, B, and C Groups randomly. Their systolic BP was 120–140 mmHg and diastolic BP was 80–90 mmHg. Preliminary data such as name, age, sex, address, weight and symptoms like headache, fatigue, exertional dyspnoea, palpitation or chest pain were recorded on individual proformas. Complete general and specific cardiovascular examination was done on all subjects.
Patients with co-morbid factors like Diabetes mellitus, Malignancy, Liver failure, Kidney failure, Pregnancy, and Patients taking Homeopathic or Ayurvedic treatment were not included in the study.
First, dried plums were pitted and packets were prepared each containing 3 prunes weighing about 11.5 gm. One packet constituted single dose and two packets taken as double dose (23 gm). Group (A) was given one packet, and the second group (C) was given
J Ayub Med Coll Abbottabad 2010;22(1)
http://www.ayubmed.edu.pk/JAMC/PAST/22-1/Talat.pdf 29
two packets. Control group (B) simply drank a glass of water early in the morning on empty stomach. Study group patients were asked to soak the contents of the packet overnight (approximately 7–8 hours) in a glass of water (250 ml). Next morning the pre-hypertensive patients were requested to drink the prune juice on an empty stomach and eat the whole fruit as well.
Three consecutive BP readings were recorded for each patient. Mean of these readings was tabulated under week 0. The patients were given instructions for use of prune juice and any clarifications necessary were provided. The patients were sent home with the instructions for a follow up visit after every two weeks when mean of three consecutive BP readings was recorded. The patients were regularly monitored fortnightly for 8 weeks. These patients were advised to take a low salt and low cholesterol diet, do regular daily exercise and visit on week 2, 4, 6 and 8 regularly for checkups. All groups were monitored in a similar fashion. These groups were matched for age, gender and weight as much as possible.
To observe the effects of prune juice on the cardiovascular system, patients from each group provided a blood sample at 0 week, and after 8 weeks treatment. Serum cholesterol, HDL, LDL, and triglycerides levels were estimated in all subjects.
Data were analysed with SPSS 10.0 using Paired-Sample t-test with 95% confidence interval.
RESULTS Study was conducted on 259 pre-hypertensive patients, 11 were missing and 248 were valid. The base line clinical picture is in Table-1.
Table-1: Baseline clinical picture
Variables Total Control Single dose
Double dose
n valid 248 missing 11
valid 98 missing 5
valid 98 missing 4
valid 52 missing 2
Age (Years) 43±10 42±10 43±9 42±12 n % n % n % n % Male 98 38.3 30 29.1 42 41.2 26 51 Female 157 61.3 72 69.9 60 58.8 25 49 Asymptomatic 86 34.5 43 44 28 28.4 15 29 Headache 128 51.4 42 43 60 60.6 26 50 Fatigue 126 50.6 45 46 53 53.5 28 54 Exertional dyspnoea 77 30.9 28 28.6 39 39.4 10 19.2 Palpitations 54 21.8 17 17.3 28 28.3 9 18 Chest pain 43 17.4 13 13.3 23 23.5 7 14
Statistically significant (p<0.05) reduction in systolic BP. (Paired-Sample t-Test) by both treated and control groups after each fortnightly tested BP, i.e., after 2, 4, 6, and 8 weeks treatment with prune or placebo (Table-2).
There was reduction of diastolic BP by all groups which was statistically significant (Paired-
Sample t-Test, p<0.05) with single dose and control groups after 2, 4, 6 and 8 weeks treatment with prunes or placebo respectively (Table-3).
After 8 weeks treatment there was significant reduction of cholesterol by both single (p=0.002) and double (p=0.003) doses; and LDL by both single (p=0.017), double (p=0.009) doses. HDL was significantly increased by control group (p=0.026). There was no significant change in triglyceride serum concentration after 8 weeks treatment with prunes or placebo by all groups. (Table-4) Table-2: Comparison of fortnightly systolic BP of
groups by Paired-Samples t-Test Group n Mean Systolic BP p
62 wk 0=134.03±1.38 wk 2=130.53±0.97 0.000
48 wk 0=133.13±1.35 wk 4=130.31±1.14 0.020
36 wk 0=133.06±1.66 wk 6=127.58±1.37 0.000
Single dose of prunes
31 wk 0=131.45±1.43 wk 8=126.70±1.02 0.004
43 wk 0=131.98±0.82 wk 2=129.76±0.84 0.012
45 wk 0=132.11±0.80 wk 4=128.22±0.85
0.000
45 wk 0=132.33±0.88 wk 6=128.80±0.87
0.000
Double dose of prunes
41 wk 0=131.83±0.83 wk 8=126.29±0.85
0.000
89 wk 0=133.15±1.08 wk 2=131.44±0.86
0.006
73 wk 0=133.56±1.29 wk 4=130.78±0.975
0.001
63 wk 0=133.33±1.40 wk 6=128.88±0.96
0.000
Control
53 wk 0=133.11±1.61 wk 8=128.33±1.03
0.000
Table-3: Comparison of fortnightly diastolic BP of groups by Paired-Samples t-Test
Group n Mean Diastolic BP p 62 wk 0=86.45±0.97
wk 2=83.72±0.85 0.000
48 wk 0=86.56±1.04 wk 4=83.35±0.77 0.000
36 wk 0=85.56±1.27 wk 6=82.22±0.83 0.009
Single dose of prunes
31 wk 0=84.84±1.36 wk 8=81.93±0.85 0.056
43 Wk 0=108.26±21.01 wk 2=85.00±1.09
0.272
45 wk 0=107.33±20.07 wk 4=84.55±0.85
0.265
45 wk 0=107.22±20.07 wk 6=83.24±0.74
0.241
Double dose of prunes
41 wk 0=108.66±22.04 wk 8=81.60±0.56
0.228
89 wk 0=86.81±0.65 wk 2=84.39±0.70
0.001
73 wk 0=86.58±0.74 wk 4=84.10±0.63
0.000
63 wk 0=87.78±0.79 wk 6=83.85±0.67 0.000
Control
53 wk 0=86.98 ±0.84 0.000
J Ayub Med Coll Abbottabad 2010;22(1)
http://www.ayubmed.edu.pk/JAMC/PAST/22-1/Talat.pdf 30
wk 8=81.96 ±0.60 wk= weeks of treatment
Table-4: Comparison of lipid profile of groups by Paired-Sample t-Test
Dependant variable Group n Mean p
Single dose 31 0 wk=189.43±7.46 8 wk=161.36 ±6.60 0.002
Control 31 0 wk=166.87±8.82 8 wk=182.32±12.74 0.266
Cholesterol
Double dose 27 0 wk=174.18±5.75 8 wk=159.33±6.38 0.003
Single dose 31 0 wk=35.80±3.07 8 wk=30.06±2.48 0.101
Control 33 0 wk=29.60±3.08 8 wk=38.63±3.35
0.026
HDL
Double dose 24 0 wk=34.91±2.96 8 wk=30.62±2.14
0.255
Single dose 31 0 week=101.61±7.20 8 week=82.06±4.61
0.017
Control 33 0 week=80.57±6.52 8 week=92.87±7.21
0.100
LDL
Double dose 24 0 week=93.37±6.06 8 week=80.20±5.88
0.009
Single dose 31 0 wk=182.38±18.52 8 wk=194.58±20.01
0.450
Control 33 0 wk=192.45±19.12 8 wk=65.48±16.01 0.243
Triglycerides
Double dose 26 0 wk=186.07±18.80 8 wk=179.65±16.48 0.749
DISCUSSION As time progresses, more and more people are searching for alternate ways for healing the diseases inflicting man. Millions of people around the world spend enormous amounts of money on allopathic medicine. Just imagine if all of this money could be saved. What if the cure for these diseases lies in our very own backyards? This very question is fuelling people to do intense research to find new treatments for these diseases, things which were not known to man a decade or two ago.
According to Mosby’s Medical Dictionary, hypertension is defined as a common disorder characterized by elevated blood pressure persistently exceeding 140/90 mmHg.6 Hypertension is a disease affecting millions of people worldwide. It is one of the leading causes of heart disease and strokes. As a result, scientists are looking for new simpler ways for combating the disease. A study done at Oxford University in the United Kingdom suggests that fruits and vegetables do have a drastic change on blood pressure.2
Bainiku-ekisu, the fruit juice concentrate of Asian plum, could represent a potential new therapeutic agent for cardiovascular diseases such as hypertension and atherosclerosis.7
Our study shows that there is significant drop in systolic and diastolic BP by lower doses of prunes. At higher doses systolic BP fell significantly,
there was also a drop in diastolic BP from 108.66±22.04 to 81.60±0.56 although statistically not significant. A reduction of 2 mmHg in diastolic blood pressure results in a decrease of about 17% in the incidence of hypertension, 6% in the risk of coronary heart disease, and 15% in the risk of stroke and transient ischemic attack.2
Novel results seen are in the control group who took a glass of water empty stomach in the morning showed significant reduction in both systolic and diastolic BP. Control group also had significant increase in serum HDL that was not seen by prune treated groups. May be the water taken on empty stomach early in the morning works, or compliance to instructions for healthy life style like low salt and low cholesterol diet, walk, exercise and reassurance by the physician by fortnightly monitoring are responsible for the effect.
Most plums, lemons, and wild grapes (Eastern Concord variety), cranberries and boysenberries are high in pectin and decrease plasma cholesterol concentration, high density lipoproteins (HDL), triglyceride concentrations and body weight, the viscosity of pectin may determine their cholesterolemic effect in hamsters.8 Plum puree and prune juice contain dietary fibre and carbohydrates.9 Fibres extracted from dried plums lower plasma LDL and liver cholesterol in rats and that is not dose related.10
In another study, an eight-week crossover trial involved 41 adult men with mild hypercholesterolemia. Plasma LDL-cholesterol was significantly lower after the dried plum (3.9 mmol/L) than the fruit juice (4.1 mmol/L).11 There was significant reduction in serum cholesterol and LDL by both lower and higher doses of prunes in our study.
Bainiku-ekisu, the fruit-juice concentrate of the oriental plum (Prunus mume) has recently been shown to improve human blood fluidity.12 Bainiku- ekisu may be beneficial against hypertension and atherosclerosis by selectively inhibiting growth promoting signals of Angiotensin-II in the vasculature.13 Experimental evidence supporting a role for oxidative stress in vascular injury and hypertension is convincing.14 The supplementation of antioxidants, particularly in the form of fresh fruit and vegetables, reduces blood pressure, supporting a role for free radicals in hypertension.15
Many constituents of prunes are identified having antioxidant properties.16–20 May be it is the antioxidant properties of prunes that they reduce both systolic and diastolic blood pressure and reduce serum cholesterol and serum low density lipoprotein.
J Ayub Med Coll Abbottabad 2010;22(1)
http://www.ayubmed.edu.pk/JAMC/PAST/22-1/Talat.pdf 31
In our study BP is reduced by both placebo and prunes but cholesterol and LDL are reduced only by the patients taking both doses of prunes. In our previous study prunes also reduced Serum ALP (alkaline phosphatase) and ALT (alanine aminotransferase).
Alanine aminotransferase predicts coronary heart disease events. A 10 year follow-up of the Hoorn Study strongly suggests that elevation of ALT and non-alcoholic fatty liver disease (NAFLD) are associated with increased risk of cardiovascular disease, and are independent predictors of cardiovascular mortality.20
Our study is in agreement with Unani Tibb for use of prunes in hypertensive patient. Use of prune is cardiovascular protective by reducing blood cholesterol and light density lipoproteins. They have added blood pressure lowering effects.
CONCLUSION Prunes reduce both systolic and diastolic blood pressure that is not different from placebo. One common factor, water, with or without prunes taken early in the morning on empty stomach might be responsible for lowering blood pressure. As prunes also significantly reduced serum cholesterol and LDL, their cardiovascular protective role is predicted.
ACKNOWLEDGEMENT We thank Ajla Wasti, Amal Iftikhar, Amin Ali Mohiuddin, Asim Arif Rizvi, Asma Rehman, Aqifa Amin, Hussain Haider, Maria Zaidi, Mahwish A Hayee, Sara Pasha, Tahmina Haq, Tahseen Talib and Ziad Umar Khan for assisting in writing the protocol of this research work. Waseem safdar (Medical Technologist) and Zubair Alam (Laboratory Assistant) for storage of blood samples, and Mr. Anees Alam, General Manager, Allied Services SIH Lab. for laboratory tests.
REFERENCES 1. Ness AR, Powles JW. Fruit and vegetables, and cardiovascular
disease: a review. Int J Epidemiol 1997;26:1–13. 2. John,J, Ziebland S, Yudkin P, Roe LS, Neil HA. Effects of fruit and
vegetable consumption on plasma antioxidant concentrations and blood pressure: a randomized controlled trial. Lancet 2002;359:1969–74.
3. Guidelines subcommittee. 1999 World Health Organization– International society of hypertension guidelines for the management of hypertension. J Hypertension 1999;17:151–83.
4. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. JAMA 2003;289:2560–71.
5. Nadkarni, AK. Indian Materia Medica, originally edited by late Nadkarni KM revised and enlarged by Nadkarni AK. 3rd Ed. Bombay: 1950. p1014–5.
6. Mosby’s Medical Dictionary, 2002. 7. Eguchi,S, Frank, G, Utsunomiya, H. Popular Japanese plum, now
available in the US, may help prevent the onset of cardiac disease. American Physiological Society 2003. available at: http://www.the- aps.org/press/conference/eb/15.htm
8. Terpstra AHM, Lapre JA, de Vries HT, Beynen AC. Dietary Pectin with High Viscosity Lowers Plasma and Liver cholesterol concentration and plasma cholesteryl ester transfer protein activity in hamsters. J Nutr 1998;128:1944–9.
9. Dikeman CL, Bauer LL, Fahey GC Jr. Carbohydrate composition of selected plum/prune preparations. J Agric Food Chem 2004.;52:853–9.
10. Tinker LF, Davis PA, Schneeman BO. Prune fiber or pectin compared with cellulose lowers plasma and liver lipids in rats with diet-induced hyperlipidemia. J Nutr 1994;124(1):31–40.
11. Tinker LF, Schneeman BO, Davis PA, Gallaher DG, Waggoner CR. Consumption of Prunes as a Source of Dietary Fiber in Men with Mild Hypercholesterolemia. Am J Clin Nutr 1991;53:1259–65.
12. Chuda Y, Ono H, Ohnishi-Kameyama M, Matsumoto K, Nagata T, Kikuchi Y. Mumefural, citric acid derivative improving blood fluidity from fruit-juice concentrate of Japanese apricot (Prunus mume Sieb. et Zucc). J Agric Food Chem 1999;47:828–31.
13. Utsunomiya H, Takekoshi S, Gato N, Utatsu H, Motley ED, Eguchi K, et al. Fruit-juice concentrate of Asian plum inhibits growth signals of vascular smooth muscle cells induced by angiotensin II. Life Sci 2002;72:659–67.
14. Rhian M. Touyz Reactive Oxygen Species, Vascular Oxidative Stress, And Redox Signaling In Hypertension, what is the clinical significance? Hypertension 2004;44:248–52.
15. Ceriello A, Diabetes Complications and Hypertension-Novel Insights into Pathophysiology and Management, Original Article: Possible Role of Oxidative Stress in the Pathogenesis of Hypertension. Diabetes Care 2008;31:S181–S184.
16. Kayano S, Kikuzaki H, Yamada NF, Aoki A, Kasamatsu K, Yamasaki Y, et al. Antioxidant properties of prunes (Prunus domestica L.) and their constituents. Biofactors 2004;21(1-4):309– 13.
17. Kayano S, Kikuzaki H, Ikami T, Suzuki T, Mitani T, Nakatani N. A new bipyrrole and some phenolic constituents in prunes (Prunus domestica L.) and their oxygen radical absorbance capacity (ORAC). Biosci Biotechnol Biochem 2004;68(4):942–4.
18. Kikuzaki H, Kayano S, Fukutsuka N, Aoki A, Kasamatsu K, Yamasaki Y, et al. Abscisic acid related compounds and lignans in prunes (Prunus domestica L.) and their oxygen radical absorbance capacity (ORAC). J Agric Food Chem 2004;52:344–9.
19. Kayano S, Yamada NF, Suzuki T, Ikami T, Shioaki K, Kikuzaki H, et al. Quantitative evaluation of antioxidant components in prunes (Prunus domesticaL.). J Agric Food Chem 2003;51:1480–5.
20. Bellentani S, Bedogni G, Tiribelli C. Liver and heart: A new link? - ALT Predicts Heart Disease. J Hepatol 2008;49(2):300–2.
Address for Correspondence: Prof. Dr. Talat Ahmed, Section Head, Pharmacology and Therapeutics, Shifa College of Medicine, Pitras Bukhari Road, Sector H-8/4, Islamabad, Pakistan. Tel: +92-51-4603403, Cell: +92-334-5344937, Fax: +92-51-4435046 Email: [email protected]
