Cardiovascular diseases, especially coronary artery disease remain the leading cause of premature death and disability among both men and women in developed nations. The data from many large scale trials, including the Framingham Heart Study indicates that the risks of coronary disease increases as blood cholesterol levels rise, and that the relationship between death from heart disease and serum cholesterol levels is continuous, graded and strong. Numerous clinical trials, including the Lipid Research Clinics Coronary Primary Prevention Trial have indicated that the clinical manifestations of heart disease, including myocardial infarction can be reduced by lowering cholesterol levels with a variety of lipid-lowering agents. The most effective class of these agents, the RMG-CoA reductase inhibitors, are very potent but produce skin rash, myalgia, abnormalities of liver function and other problems in a small proportion of patients. The cost of these drugs may also be of significant concern, especially in view of the long-term nature of the therapy.

Garlic:(allium sativum), as a therapeutic agent has long been advocated but only recently studied as a treatment for a variety of health-related problems. It has a unique odour, is inexpensive and widely grown throughout the world, but its potency is variable thus necessitating administration by standardised garlic powder tablets for clinical efficacy trials. The ability of standardised garlic powder tablets to significantly lower serum cholesterol has been reported in double-blinded, placebo-controlled clinical trials in Germany, Britain and the United States. including meta-analyses which have been favourably significant. These results prompted us to undertake a Canadian study to assess their potential benefit in a group of hyperlipidemic patients.

The study was designed as a randomized, double-blinded placebo-controlled comparison of the effect of the garlic powder tablet LI-114, (Kwai, Lichtwer Pharma GmbH, Berlin, Germany) and a placebo, on the serum lipid values in patients with hyperlipidemia, conducted in a single centre cross-over trial. Referred patients with known hyperlipidemia and volunteers with an abnormal high lipid profile upon entry criteria screening laboratory profile were included in the study. There were 19 patients, ranging in age from 41-77 years with nine males and ten females. Main outcome measures: lipid-lowering properties of garlic powder tablets by 30 day analysis for a total of 120 days on serum cholesterol, triglycerides, HDL & LDL fractions.There were 34 volunteers who met the entry criteria of elevated cholesterol, off all drug therapy and willing to participate in a blinded study. Informal consent was obtained and baseline parameters were taken, including history, physical examination and biochemical lipid profiles in a fasting state. There were 19 patients who completed the entire 120 day fully blinded protocol. The remaining 15 patients chose to unblind themselves and switch to known active garlic powder tablets. They were thus eliminated from consideration in the study results. For the first 30 days, patients were randomised to either the garlic powder tablets or placebo powder tablets 300 mg, three times daily (TID). At Day 30, both groups were switched to active garlic powder tablets LI-114, 300 mg TID. On Day 60, the blindly labelled bottles of either placebo or active garlic powder tablets were resumed, 300 mg TID-biochemical lipoprotein profiles were obtained at each 30 day visit. The clinical history, pill compliance, weight, blood pressure and diet status were reviewed by a cardiovascular nurse practitioner and recorded.

Blinded number-labelled bottles were supplied with a standardised identical essentially odourless tablet of either placebo or active garlic powder (LI-114) in doses of 300 mg each. Patients were given enough pills to last the entire 120 days of the trial.

Total serum cholesterol levels decreased by 12% (p< 0.03) on average at day 120 in the active treatment group, from average 6.99 (+/- 1.44) mmol/L at baseline to 6.09 (+/- 1.01) mmol/l. The placebo group did not have a significant decrease in cholesterol or triglyceride levels from baseline to any subsequent time point. Nine patients were in the active treatment group, while ten received placebo in the two cross-over intervals of the trial. Average patient age was 54 +/- 8.3 years, ranging from 41 - 77 years. The percentage change from baseline for serum cholesterol are presented in Table 1. The mean percentage decrease for the LI-114 group ranged from approximately 7% to approximately 12% at each time point, with the exception of day 60 where the mean percentage decrease was approximately 5:% +/- 12.27%. In the placebo group the mean percentage difference from baseline ranged from an increase of approximately 7% to a decrease of approximately 3%. Figure 1 shows the graph of declining mean serum cholesterol levels from baseline values over the study period.

Click here for Figure 7 - Serum Cholesterol Level

The triglyceride levels fluctuated variably, but over the course of treatment, neither the LI-114 treatment group nor the placebo group displayed any statistically significant changes in triglyceride levels. The serum levels of HDL fractions were also studied. Although the mean change from baseline for HDL serum levels in the active treatment group increased steadily to 0.22 +/- 0.51 mmol/L at Day 120, with mean baseline percentage changes from 104% to 137%, these results did not reach statistical significance (p< 0.22). The change from baseline for the placebo group was not significant. Patient weight was measured on Day 0 of study treatment, and on Day 120 at the final visit. Continuous weight counselling took place during each study visit. There was a mean increase of 0.45 +/- 2.39 kg for the LI-114 treatment group and a mean increase of 0.45 +/- 2.44 kg for the placebo group. A statistical significance of p > 0.57 was calculated for this efficacy variable.

The medicinal use of garlic can be traced to ancient Egypt with written records from 1550 BC. Animal studies have suggested that allicin, the principal active ingredient in garlic, functions metabolically like a weak HMG-CoA reductase inhibitor. Sterol synthesis and the liver enzymes. Crushing the garlic clove or bulb releases the enzyme allinase, converting inactive alliin to the biologically active allicin. Human studies on normolipidemic subjects showed allicin's ability to decrease the susceptibility of apolipoprotein B- containing lipoproteins to oxidation, reducing free radicals, which in oxidation of LDL, participate in plaque formation in atherosclerosis. Garlic has also been proven to decrease fibrinogen and fibrinopeptide A levels, increase the fibrinolytic activity and reduce systolic and diastolic blood pressure. A significant decrease in serum cholesterol was achieved within one month of treatment with 900 mg/day of LI-114 garlic powder tablets (equivalent to about 2.7g grass fresh garlic). A 12% reduction in cholesterol levels from baseline over 120 days was shown to be produced, while HDL levels rose, but not to a statistically significant degree. There was no significant effect on serum triglycerides. Patients weight remained reasonably controlled and no other drugs were used. Tolerance of the preparation was uniformly excellent with no reports of adverse effects or odour.

These results are consistent with other similar studies and may be about the best degree of reduction that can be obtained by garlic therapy alone. However, a therapeutic reduction in serum lipid levels greater than 12% is often required and thus patients may need more aggressive management to obtain lower cholesterol levels. There are significant benefits to be achieved with standard drug medication therapies for hyperlipidemia, but well documented adverse effects can limit their use and a certain percentage of patients are unable to tolerate these drugs. We believe that garlic powder tablets have a role in cholesterol management as adjunctive therapy in most cases of significant hyerlipidaemias. Strict dietary compliance and lipid-lowering drugs remain the primary recommendations. When patients have milder elevations of lipid levels or are intolerant to conventional medication, garlic therapy may provide a safe, effective alternative to standard agents. Supplemental standardised tablets with a known quantity of allicin offer the most reliable route of delivery of this antilipidaemic substance. Further scientific studies with appropriate critical peer review should be performed in determining the ultimate role of these treatments in the future.