EDITOR'S NOTE: One of the major themes of totalhealth is to create an awareness of intergration medicine as the paradigm for health care in the new millenium. The organizers of the Corporate Alliance for Integrative Medicine outlined below should be applauded for their pioneering effort.

While you may find the acommanying research study on garlic somewhat techincal, it is not only significant, but an excellent example of the application of the integrative approach in that it establishes supplementation as both a safe alternative as well as a complement to drug therapy.

Sarasota, FL (June 16, 1998). Created to increase knowledge and awareness of the efficacy and safety of herbs, vitamins and other dietary supplements among the medical profession and the general public, the Corporate Alliance for Integrative Medicine, Inc. has been founded by 10 of the industry's leading dietary supplement manufacturers and suppliers.

Founding members include: Botanicals International; East Earth Herb, Inc.; Natrol, Inc.; Nature's Herbs, Inc.; Nature's Way products, Inc.; NuSkin, Inc.; Nutraceutical, Inc.; Pure World, Inc./Madis Botanicals, Inc.; Rexall Sundown, Inc.; Weider Nutrition International, Inc. The Alliance was conceived and initiated by InterShow, Inc., a leader in creating dynamic market places.

Established as a not-for-profit corporation, the Corporate Alliance will focus its objectives by founding research programs at major universities nationwide. These programs will be dedicated to the study of dietary supplements. The Corporate Alliance will also fund and develop education initiatives to inform medical professonals and consumers about the results of research in these areas.

According to Jennifer Cooper, president of the Alliance, "The Alliance is strengthened by the participation of major, sometimes competitive, leaders of the dietary supplement industry who have agreed to come together to promote the finest research and educational initiatives possible. We are committed to assisting medical professionals and consumers in making the best decisions about dietary supplements and look forward to funding a variety of Corporate Alliance for Medicine programs."

Hyperlipidemia is a common problem in renal transplanet recipients.¹ Cardiovascular disease accounts for about 40 percent of deaths in this group of patients.² In the general population, it has been well documented that prolonged elevations of lipids are a risk factor for atherosclerosis and death from coronary heart disease. Furthermore, an analysis of the Framingham Heart Study shows that the hypothetical benefits of cholesterol reduction are greatest when the underlying risk for coronary disease is the greatest.³ It is reasonable to assume that hyperlipidemia poses a similar risk to transplant recipients and that such patients may also benefit from cholesterol reduction.

The pathogenesis of hyperlipidemia in renal transplant patients is not fully understood, but is most likely multifactorial. A correlation with steroid dosage has been found in some studies⁴ but not in others.⁵ Similarly, some investigators have found cyclosporine to be an important factor,⁶ whereas others have not.⁴ Other factors to be considered include obesity, diabetes, nephrotic syndrome, declining renal function, antihypertensive medications and pretransplant hyperlipidemia.

The treatment of hyperlipidemia in transplant recipients has been problematic. Dietary therapy is often only partially effective.⁷ Bile binding resins may potentially interfere with cyclosporine absorbtion. In a study of cardiac transplant recipients nicotinic acid was discontinued in 11 of 17 patients because of problems with hyperglycemia.⁸ The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been used successfully,^9,10,11 but several cases of rhabdomyolysis have been reported in cardiac transplant recipients receiving high doses or concomitant therapy with other hypolipemic agents.^{12, 13}

In view of the problems associated with the treatment of hyperlipidemia in transplant patients, it would be desireable to identify safe and effective alternative modalities. Garlic has been used for centuries as an herbal medicine.¹⁴ In the past 10 years a number of trials have been performed evaluating the efficacy of garlic for treating hypercholesterolemia. In a meta-analysis of five homogeneous trials (n=410 patients), Warshafsky et al. found that garlic therapy was associated with a decrease in total cholesterol of about nine percent.¹⁵ In addition, a recently published randomized double-blind trial found that treatment with garlic at a dose of 900 mg/day (equivalent to approximately one clove of fresh garlic) was associated with a significant reduction in total cholesterol and low-density (LDL) cholesterol.¹⁶ In the reported studies there were no adverse affects seen with garlic therapy and no significant odor problems. Because of the beneficial impact of garlic seen in these studies, we chose to study the efficacy of garlic supplementation in hypercholesterolemic renal transplant patients.

We selected 35 renal transplant patients with a total serum cholesterol of greater than 240 mg/dL and LDL cholesterol of greater than 160 mg/dL by two consecutive fasting determinations. All participants had stable renal allograft function for more than a six-month period. Exclusion criteria includes: triglyceride elevations of greater than 500 mg/dL, nephroticsyndrome and use of other hypotipemic medications within a six month period. The immunosuppressive regimen in these patients included cyclosporine, prednisone and azathioprine or misoprostol. Patients were instructed in a Step One National Cholesterol Education Program reduction diet and randomized to receive a 12-week course of either placebo or matching garlic tablets (PureGar®, Tacoma, Washington) at a dose of 580 mg two times a day which is equivalent to 4080 ug pf allicin per day. Intragroup analyis was performed by analysis of variance with repeated measures, followed by the Duncan test. Intergroup analysis was compared by unparied t test. A difference was considered statistically significant when the P value was <.05. Data was analyzed by paired t test using Sysart program.

Baseline data for placebo and garlic groups are provided in Table 1. The two groups were well matched except that high density (HDL) cholesterol levels were significantly higher in the garlic group, but the difference was not statistically significant. Garlic was effective in decreasing both total and LDL cholesterol levels (Table 2). This benefit was apparent after six weeks of therapy and sustained at 12 weeks. In contrast, total cholesterol and LDL cholesterol levels did not change significantly in the placebo group.

Table 1. Baseline Date for Placebo and Garlic Groups
	Placebo (n = 16)	Garlic (n = 19)
Age (y)	48 ± 3	48 ± 2
Gender (male/female)	9/7	8/11
Weight (lbs)	185 ± 8	181 ± 10
Year posttreatment	4 ± 1	3 ± 1
Prednisone dose (mg/d)	14 ± 1	14 ± 1
Creatinine (mg/dL)	1.9 ± .02	1.5 ± 0.1
Cholesterol (mg/dL)	290 ± 9	290 ± 8
Triglycerides (mg/dL)	277 ± 21	227 ± 18
LDL (mg/dL)	182 ± 7	193 ± 8
HDL (mg/dL)	48 ± 3	80 ± 4*

Table 1 data are presented as mean (mg/dL) + SEM *P < .05 vs baseline



Table 2. The effect of garlic and placebo therapy on total (A) and LDL cholesterol (B) over 12 weeks. (*P < .05 vs baseline).

In general, garlic therapy was well tolerated. One patient complained of diarrhea and a second patient complained of epigastric pain. In both, the complaints resolved with a decrease in the dose frequency to once daily. The lack of response seen in the placebo group is in accord with previous studies in which the response to dietary intervention alone is at best only partially successful.⁷ The magnitude of the response to garlic was somewhat less than that reported in the meta analysis in which garlic was found to decrease total cholesterol by 9 percent.¹⁵ Most likely this difference is related to the more severe hyperlipidemia seen in renal transplant recipients. However, it is possible that even small decrements in cholesterol may have a long-term beneficial impact, particularly in a population that is at higher risk of coronary disease.

Although garlic had significant beneficial effects, treated patients still had hyperlipidemia which was severe enough to consider the addition of standard pharmacotherapy. In view of our findings, there may be a role of combining garlic therapy with a HMG-GoA reductase inhibitor. It is possible that garlic supplementation could decrease the dosage of the HMG-CoA reductase inhibitor required to achieve an adequate response and thereby minimalize the chance for drug toxicity. Future studies will be needed to evaluate the efficacy of such a strategy.