Effects of Garlic and Trikatu on Plasma Lipid Levels - Research Proposal Example

Effects of Garlic and Trikatu on Plasma Lipid levels Objectives: To study the effects of Garlic and Trikatu: a compound of black pepper (piper nigrum), long pepper (piper longum) and ginger (zinziber officinale) on plasma lipid levels of mildly hypercholesterolemic British Asian men. Hypothesis: Garlic decreases levels of total serum cholesterol and LDL cholesterol and raises HDL cholesterol. Garlic and Trikatu in combination further decreases levels of total serum cholesterol and LDL cholesterol and raises HDL cholesterol. Introduction: Cardiovascular diseases have been increasing in number throughout the years, primarily due to the poor lifestyle we lead of food choice and no exercise program to be followed. Other factors do have their effect too, such as hereditary factors and congenital causes. According to the World Health Organization (WHO) in 2003 an estimation of 16.7 million people die each year from cardiovascular diseases. 1And it is percepted that by 2030 24 million people will suffer and eventually die as a consequence to this disease. 2 United Kingdom has registered one of the highest death rates in the world as registered by Poulter 20033. He claims this is due to the “high levels of standard risk factors and a low level of intervention on those risk factors.” Of those factors he mentions dyslipidaemia (particularly high LDL cholesterol and low HDL cholesterol), smoking, hypertension, glucose intolerance, and central obesity. CVD accounted for more than 233,000 deaths in the United Kingdom (UK) in 2003. Thirty-eight percent of deaths are from CVD, and 34 percent of premature deaths in men and 25 percent in women are from CVD. 4 It is also seen by Poulter that young women are at higher risk of these diseases compared to older men, and the medical intervention is inversely propotional in regards to who deserves the utmost urgent treatment. Increase in cardio vascular disease in British Asian men – migrant community and the effects of lifestyle changes and diet leading to risk factors and cardio vascular disease In an article, a study conducted by University of Manchester's medical school states that people who move from South Asia into the UK actually increase their risk of attaining cardiovascular disease. 5 Significance of plasma lipid levels on cardio vascular disease, identifying low risk and high risk lipid levels Plasma lipid level has great impact on the health of cardiac muscle. The heart and vascular components in that areas are greatly affected by any increase of the lipid content especially cholesterol. This is because lipids may adhere to the walls of the coronary arteries and form a plug decreasing the amount of blood that can pass from there causing hypoxia and death of tissues there due to lack of oxygen supplementation. Two lipid profiles exist; the LPD which is the worse type and should be maintained at as low level as possible, the other HPD which is the good type and aids in the health of the cells. Effects of Statin and other cholesterol lowering drugs Statins such as Liptor, Zicor, Lovastatin, a cholesterol LPD lowering, hypolipidemic drug is used mainly to decrease the cholesterol level by inhibiting the HMG-CoA reductase enzyme which inhibits the production of cholesterol by so resuce cardiovascular diseases risks. Side effects to this family of drugs range from constipation, diarrhea, gases, headaches, nausea, decreased sexual ability, insomnia, fever, and muscle cramps. Importance of lowering and maintaining reduced cholesterol by diet and food supplements like garlic and black pepper, long pepper and ginger – common spices used in Asian diets “Research shows a strong relationship between high cholesterol and heart disease. It is now clear lowering cholesterol levels in the blood has significant health benefits. This applies not only to people who have had a heart attack or stroke but to those who want to avoid such an event happening.” lowering cholesterol levels can be achieved either by dietary change or medications. Asian spices such as tumeric, have been used for years in the Chinese herbal medicine to treat inflammation, infections, and various gastrointestinal ailments and is recently being investigated as a possible cholesterol lowering agent. (Moll, Jennifer 2007) Effects of garlic on raised cholesterol levels. Garlic had shown many positive signs of lowering the cholesterol level in hypercholesterolemia cases in many studies. In a study conducted by Mahmoodi M, Islami MR, Asadi Karam GR, Khaksari M, Sahebghadam Lotfi A, Hajizadeh MR, Mirzaee MR 20066, showed a decrease in serum lipids but garlic cannot be used solely as a therapeutic agent. But Gardner CD, Lawson LD, Block E, Chatterjee LM, Kiazand A, Balise RR, Kraemer HC. 20077 did a study to investigate the effect of raw and processed garlic on such high cholesterol cases and found out no significant effect on the LCD or plasma lipid profile. Effects of Trikatu on raised cholesterol levels. Trikatu, a combination of Piper longum (fruit), Piper nigrum (fruit) and Zingiber officinale (rhizome) dry powder, was found to be of great benefit as a hypolipideamic agent confirms a study done by Sivakumar V, Sivakumar S. 20048. Any toxic or side effects identified through previous clinical trials? Of Garlic or trikatu? Allergic reactions such as chelitis have been reported on the use of garlic 9. Also prolonged application of garlic on skin especially its extract Allicin may cause skin burns. Some people even experiences gastrointestinal discomfort. High concentrations of garlic have illustrated toxic and fatal effects on animals. More research needs to be conducted on this issue.10 Background: Studies have shown the benefits of garlic on lipid profile by decreasing LDL levels and raising HDL levels. Aged garlic has shown better results. Trikatu is an ayurvedic compound known to increase absorption and bioavailability of drugs and is often prescribed with other formulations by ayurvedic doctors. Asian men are pre-disposed to raised cholesterol levels and cardio vascular disease, especially migrant British Asian men. The Problem: The importance of diet and lifestyle on reducing raised cholesterol risk factors for cardio vascular disease The success rate of modified diet and exercise programmes on reducing and maintaining raised cholesterol levels. If food supplements like garlic and Trikatu (commonly used Asian spices) can further help reduce raised cholesterol and prevent the intake of statin and other cholesterol reducing drugs Garlic is known to reduce moderately raised cholesterol. Various forms of garlic have been tested (fresh, extracts, aged etc) Identify form, dose and duration of successful trials. Any trials on mildly raised cholesterol levels? No trials of garlic with trikatu to measure effects Questions: does garlic taken with trikatu have a better result in reducing raised cholesterol in British Asian men? Are the results clinically significant to introduce increased garlic and trikatu consumption in the diet of hypercholesterolemia of Asian men? The Study Design: Experimental study to observe the effects of garlic and garlic/trikatu on plasma lipid levels of mildly cholesterolemic British Asian Men Identify Asian men who have recently been diagnosed with mildly raised cholesterol levels by their doctors These men will be identified through placing an advertisement in the local Asian paper (Gujarat samachar) OR be identified by a local clinic in a generally populated Asian area. Written consent will be taken from the participants and their GP. Confidentiality will be maintained by coding the diet data sheets and any other data collection documentation. Participants will be advised on their right to withdraw from the study. In the case of queries during the study, contact numbers of the researcher will be given to all participants. Ethical permission from the relevant ethical committees (will be named): University will be taken prior to the study. All participants will have received standard dietary and lifestyle guidelines from their GP’s. The study will run for a total of 16 weeks including 4 weeks of stabilizing followed by 12 weeks of the experimental/control study. All participants will be put on a diet stabilising period for 4 weeks prior to the experimental intervention. Diet compliancy and intake will be monitored through a data sheet where common Asian foods will be listed. Participants will be asked to monitor intake on a weekly basis and submit data sheets at the end of every 4 weeks for a total of 12 weeks. Garlic and garlic/trikatu supplements in the form of tablets will be given to all the participants. Written instruction on how/when these are to be taken will be provided. Tablets will be given on a 4 weekly basis for 12 weeks and compliancy and intake will be monitored on the refill of these supplements at the end of every 4 weeks. The setting: Measurement Procedures: Participants will have had a blood test prior to selection. The doctors prior to the selection into the study using the standard instruments used nationally will measure plasma lipid levels. Identify this method/instrument. Total cholesterol levels, LDL and HDL levels will be used. Participants will be requested to go for a blood test at the end of 4 weeks. Plasma lipid levels will be again be measured at the end of the 4 weeks of stabilizing of all participants to ensure baseline starts. Blood test will again be repeated at the end of 12 weeks to measure results of the intervention. Total cholesterol, LDL and HDL will be measured for selection, after stabilising (4 weeks) and at the end of the experimental study (12 weeks) Diet compliancy will be measure/monitored using a data sheet for both groups over the 16 weeks. Sampling: Identify size of the sampling population (if known) 40 participants will be selected, with 20 in each group. This is to allow for any dropouts/ exclusions. Study aims to have a total of 30 participants with 15 in each group at the end of the study to identify any significant difference. Inclusion criteria: Men from an Asian descent, between 35 – 50 years. Otherwise healthy with recently diagnosed (between 1-6 weeks) of mildly raised cholesterol levels: check the national guidelines of mildly raised cholesterol. Current guidelines from the National Institute of Clinician Excellence states: Participants will have been given dietary guidelines by their GP’s and will be on observation to return for a blood test in 6 months – 1 year. This can be a longitudinal study. If results are needed in a shorted duration, a cross sectional study can be conducted. Exclusion will be participants with any other chronic conditions like hypertension, cardiac problems etc. Or those who are on any prescribed medication for any condition. This minimizes identified systemic conditions that can affect the study. Sampling method to be used is the blind randomized method to minimize the bias. The participants will be divided equally without revealing their identity into equal groups according to the group they are randomly assigned to. Analysis of data: Identify strategy for data analysis. Specify data analysis: manually and by computer. For computer analysis, Microsoft excel program and statistical procedures are to be performed on the data to allow effective analysis and contrasting of information to be done. Tables of samples clearly showing the number of individuals, age, sex, etc can be used. Total cholesterol levels, LDL levels, HDL levels will be used to identify any statistical difference in the group with garlic only against the group with garlic and trikatu. Comparision of before and after use of garlic can be illustrated in diagrams and statistical tools. Main variables: Diet and garlic Diet and garlic with trikatu Structure of report: Identify structure of the report/finding The report would handle the aim and method of implementing this study. The subject would be identified with the criteria of choosing them. Margin errors should be mentioned. Result of this study will be concluded at the end, seeing if the purpose of this study is reached or not. What modifications could have been made to make the study more reliable and the outcome recording more accurate must be mentioned too. The factors that could have contributed to decrease the reliability of this study are discussed, suggestions of trying to control these factors can be suggested in future researches concerning this subject/ Problems and limitations: Securing permission from the GP to conduct study in alliance with the clinic? Sample collection. Small number of participants to be chosen (40) Number of Asian men willing to undergo this research and consent to its terms might be limited and not as required. Not enough time might be present to make this a longitudinal stude, therefore it should be cross sectional. Cross sectional studies are not very reliable Compliancy of diet and lifestyle? Difficult for Asian men? Accuracy of diet records Follow up problems Life style modification of volunteers may not be as wanted, error margins may be increased. Diet choices of the individuals may have direct and indirect effect on this study, therefore other contributing factors may no be identified. Method of sampling: through advertising has selection bias. Getting the required sample, as Asian men may not go for a routine blood test unless related to another condition. Limitations: Not a clinical study and so threats to reliability and validity Dietary compliance is retrospective so can have recall bias References Aboul-Enein BH, Aboul-Enein FH. (2005) Allium sativum: nutritional properties. Clin Nutr. 24(6):1111-2. Artz MB, Harnack LJ, Duval SJ, Armstrong C, Arnett DK, Luepker RV. (2006) Use of nonprescription medications for perceived cardiovascular health. Am J Prev Med. 30(1):78-81. Atal CK, Zutshi U, Rao PG. (1981) Scientific evidence on the role of Ayurvedic herbals on bioavailability of drugs. J Ethnopharmacol. 4(2):229-32. Atlas of Heart Disease and Stroke, WHO, September 2004 Blomhoff R. (2005) Dietary antioxidants and cardiovascular disease. Curr Opin Lipidol. 16(1):47-54. Review. British Heart Foundation. Coronary Heart Disease Statistics, 2005 Edition. Borek C. (2006) Garlic reduces dementia and heart-disease risk. J Nutr.136 (3 Suppl):810S-812S. Ekeowa-Anderson AL, Shergill B, Goldsmith P.(2007) Allergic contact cheilitis to garlic. Contact Dermatitis. 56(3):174-5 Espirito Santo SM, van Vlijmen BJ, Buytenhek R, van Duyvenvoorde W, Havekes LM, Arnault I, Auger J, Princen HM. (2004) Well-characterized garlic-derived materials are not hypolipidemic in APOE*3-Leiden transgenic mice. J Nutr. 134(6):1500-3. Gardner CD, Messina M, Lawson LD, Farquhar JW. (2003) Soy, garlic, and ginkgo biloba: their potential role in cardiovascular disease prevention and treatment. Curr Atheroscler Rep. 5(6):468-75. Review. Gardner CD, Lawson LD, Block E, Chatterjee LM, Kiazand A, Balise RR, Kraemer HC. (2007) Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial. Arch Intern Med. 167(4):346-53. Izzo AA, Di Carlo G, Borrelli F, Ernst E. (2005) Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction. Int J Cardiol. 98(1):1-14. Review. Johri RK, Zutshi U. (1992) An Ayurvedic formulation 'Trikatu' and its constituents. J Ethnopharmacol. 37(2):85-91. Review. Karan RS, Bhargava VK, Garg SK. (1999) Effect of trikatu, an Ayurvedic prescription, on the pharmacokinetic profile of rifampicin in rabbits. J Ethnopharmacol. 64(3):259-64. Lala LG, D'Mello PM, Naik SR. (2004) Pharmacokinetic and pharmacodynamic studies on interaction of "Trikatu" with diclofenac sodium. J Ethnopharmacol. 91(2-3):277-80. Lau BH. (2006) Suppression of LDL oxidation by garlic compounds is a possible mechanism of cardiovascular health benefit. J Nutr. 136(3 Suppl):765S-768S. Lisa Ganora (2006) Alliin and Allicin, two important sulfur compounds from Garlic (Allium sativum) The Phytochemistry of Herbs retrieved April 28 2007 from http://www.herbalchem.net/GarlicIntroductory.htm Mahmoodi M, Islami MR, Asadi Karam GR, Khaksari M, Sahebghadam Lotfi A, Hajizadeh MR, Mirzaee MR (2006) Study of the effects of raw garlic consumption on the level of lipids and other blood biochemical factors in hyperlipidemic individuals. Pak J Pharm Sci. 19(4):295-8. Moll, Jennifer (2007), Can Turmeric Lower Cholesterol Levels?, About, retrieved 27 April 2007 from http://cholesterol.about.com/od/naturalalternatives/a/turmeric.htm Mousa AS, Mousa SA. (2005) Anti-angiogenesis efficacy of the garlic ingredient alliin and antioxidants: role of nitric oxide and p53. Nutr Cancer. 53(1):104-10. Ou CC, Tsao SM, Lin MC, Yin MC. (2003) Protective action on human LDL against oxidation and glycation by four organosulfur compounds derived from garlic. Lipids. 2003 Mar;38(3):219-24. Pharand C, Ackman ML, Jackevicius CA, Paradiso-Hardy FL, Pearson GJ; Canadian Cardiovascular Pharmacists Network. (2003) Use of OTC and herbal products in patients with cardiovascular disease. Ann Pharmacother. 37(6):899-904. Poulter, N. (2003) Global risk of cardiovascular disease Heart by BMJ Publishing Group & British Cardiac Society 89:ii2 Rahman K, Lowe GM. (2006) Garlic and cardiovascular disease: a critical review. J Nutr. 136(3 Suppl):736S-740S. Review. Ramaa CS, Shirode AR, Mundada AS, Kadam VJ. (2006) Nutraceuticals--an emerging era in the treatment and prevention of cardiovascular diseases. Curr Pharm Biotechnol. 7(1):15-23. Review. Rassoul F, Salvetter J, Reissig D, Schneider W, Thiery J, Richter V. (2006) The influence of garlic (Allium sativum) extract on interleukin 1alpha-induced expression of endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Phytomedicine. 13(4):230-5. Sangeetha T, Darlin Quine S. (2006) Preventive effect of S-allyl cysteine sulfoxide (alliin) on cardiac marker enzymes and lipids in isoproterenol-induced myocardial injury. J Pharm Pharmacol. 58(5):617-23. Sivakumar V, Sivakumar S. (2004) Effect of an indigenous herbal compound preparation 'Trikatu' on the lipid profiles of atherogenic diet and standard diet fed Rattus norvegicus. Phytother Res. 18(12):976-81. Sobenin IA, Prianishnikov VV, Kunnova LM, Radinovich EA, Orekhov AN. (2005) [Reduction of cardiovascular risk in primary prophylaxy of coronary heart disease] Klin Med (Mosk). 83(4):52-5. Russian. Stys T, Stys A, Kelly P, Lawson W. (2004) Trends in use of herbal and nutritional supplements in cardiovascular patients. Clin Cardiol. 27(2):87-90. Sun X, Ku DD. (2006) Allicin in garlic protects against coronary endothelial dysfunction and right heart hypertrophy in pulmonary hypertensive rats. Am J Physiol Heart Circ Physiol. 291(5):H2431-8. Tapsell LC, Hemphill I, Cobiac L, Patch CS, Sullivan DR, Fenech M, Roodenrys S, Keogh JB, Clifton PM, Williams PG, Fazio VA, Inge KE. (2006) Health benefits of herbs and spices: the past, the present, the future. Med J Aust. 21;185(4 Suppl):S4-24. Review. Tattelman E. (2005) Health effects of garlic. Am Fam Physician. 1;72(1):103-6. Review. van Doorn MB, Espirito Santo SM, Meijer P, Kamerling IM, Schoemaker RC, Dirsch V, Vollmar A, Haffner T, Gebhardt R, Cohen AF, Princen HM, Burggraaf J. (2006) Effect of garlic powder on C-reactive protein and plasma lipids in overweight and smoking subjects. Am J Clin Nutr. 84(6):1324-9. WHO, Cardiovascular Disease Prevention and Control. www..who.int Williams MJ, Sutherland WH, McCormick MP, Yeoman DJ, de Jong SA. Aged garlic extract improves endothelial function in men with coronary artery disease. Phytother Res. 19(4):314-9. Yadav RK, Verma NS. (2004) Effects of garlic (Allium sativum) extract on the heart rate, rhythm and force of contraction in frog: a dose-dependent study.Indian J Exp Biol. 42(6):628-31. Yeh GY, Davis RB, Phillips RS. (2006) Use of complementary therapies in patients with cardiovascular disease. Am J Cardiol. 1;98(5):673-80. Yeh YY, Yeh SM. (2006) Homocysteine-lowering action is another potential cardiovascular protective factor of aged garlic extract. J Nutr. 136(3 Suppl):745S-749S. Zahid Ashraf M, Hussain ME, Fahim M. (2005) Antiatherosclerotic effects of dietary supplementations of garlic and turmeric: Restoration of endothelial function in rats. Life Sci. 8;77(8):837-57. Read More