Clinical Studies

• Mary Lake Polan, MD, PhD, MPH, Professor and Chair of Gynecology and Obstetrics at Stanford University conducted a 30-day, double-blind study. During this study 93 women and their doctors did not know who was receiving the placebo and who was receiving the ArginMax. At the end of the study, 62% of the group that received the supplement reported greater satisfaction with their overall sex life compared with 38% in the placebo group. 64% of those in the ArginMax group reported improvement in their level of sexual desire compared with 43% in the placebo group. Of those women who were nearing menopause and were in the ArginMax group, 91% reported an increase in the frequency of intercourse compared with 20% in the placebo group. Participants also indicated improvement in degree of clitoral sensation, reduction of vaginal dryness, and satisfaction with sexual relationships.
• A study of the effects of ArginMax was conducted by Thomas Ito, MD, Dept of Urology, Kaye Kawahara, MD, Dept of Medicine of John A. Burns School of Medicine, University of Hawaii and A. Das, MD of Dept of Urology, Albany Medical College and W. Strudwick MD of U.S. Track & Field Team. Published in the Hawaii Medical Journal, the study showed that a month of supplements containing ginkgo biloba, American & Korean ginseng, L-Arginine, and vitamins A,C, E, B-complex, selenium and zinc improved the ability to maintain an erection in nine out of 10 men. Three in four men were overall more satisfied with their sex lives.
• More studies are currently being conducted.

Aileen S. Trant, PhD, Mary Lake Polan MD, PhD* *Dept of Gyn/Ob, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, CA, 94305

Introduction:

A follow-up double-blind, placebo-controlled study was conducted examining the role of dietary supplementation in female sexual function. ArginMax is a natural nutritional supplement which consists of standardized extracts of Ginkgo biloba, Korean ginseng, Damiana, L-arginine, calcium, iron, zinc, and multi-vitamins.

Methods:

Ninety-three (93) participants, age 22-73 years, were enrolled consecutively with participation open to any individuals experiencing some lack of sexual desire. Evaluations were conducted using the Female Sexual Function Index (FSFI), a validated instrument used for the evaluation of sildenafil (Viagra) in women.

Results:

Of the 93 participants, 46 received ArginMax and 47 received placebo; 58 were self reported as premenopausal (PRE), 16 as perimenopausal (PERI), and 19 as postmenopausal (POST). PERI women on ArginMax reported the largest number of improvements, as a group, including increases in frequency of sexual desire (73% of group), satisfaction with sexual relationship (73% showed improvement), and degree of clitoral sensation (73% increased). PRE women on ArginMax improved primarily in satisfaction with overall sex life (67% increased). POST women, as a group, reported the least degree of improvement, but still showed 64% increase in satisfaction with sexual relationship (as compared to 33% on placebo). Overall, PRE and PERI women on ArginMax reported 71% increase in sexual desire and 68% increased in satisfaction with overall sex life (vs. 49% and 36%, respectively, in placebo group).

Conclusions:

Nutritional intervention has a positive effect on both sexual desire and satisfaction, particularly in pre- and peri-menopausal women. Further investigation of differences related to menopause status is warranted. *Study results presented at Boston University Medical School symposium on New Perspectives in the Management of Female Sexual Dysfunction, 10/28/00

Ito, T. (Department of Urology, John A. Burns School of Medicine, University of Hawaii, Hawai) Kawahara, K. (Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Hawai) Das, A. (Department of Urology, Albany Medical College, USA) Strudwick, W. (U.S. Track & Field Team Physician, USA)

Abstract

This study reports results from an ongoing clinical study evaluating the role of natural dietary supplements in male sexual function. ArginMax (Daily Wellness Company), is a dietary supplement consisting of highly standardized extracts of ginkgo biloba (24% flavone glycosides, 6% terpene lactones), Korean ginseng (Panax Ginseng-30% ginsenosides), American ginseng (Panax Quinquefolius- 5% ginsenosides), L-arginine, vitamins ACE, B-Complex, zinc, and selenium. Based on literature review, ingredients in ArginMax may provide the substrates for nitric oxide (NO) production and up-regulate the NO pathway to facilitate smooth muscle relaxation, vascular dilatation, and improved erections. 25 urology clinic based participants from open enrollment of individuals diagnosed with mild to moderate erectile dysfunction of all etiology were recruited. Age: 40-77. Progress was measured using International Index of Erectile Function (IIEF), an instrument validated for the measurement of sexual function. Following 4-weeks of BID regimen of ArginMax, 21 subjects completing the study were evaluated. Using IIEF criteria, 88.9% of subjects experienced improvement in ability to maintain erection during intercourse. 75.0% of subjects experienced improvement in satisfaction with overall sex life. No reports of headaches, nausea, stomach upset, changes in blood pressure, cardiovascular complications, disturbed vision, or dizziness were noted.

The Effects of ArginMax, A Natural Dietary Supplement for Enhancement of Male Sexual Function

Introduction

It has been reported in the literature that dietary supplementation with certain botanical extracts, vitamins, or amino acids have led to modest improvements in male sexual function. No studies, however, have examined a systematically designed combination of natural products for the enhancement of male sexual function. Based on the proposed and elicited mechanisms of various natural products in the literature, we postulated that a combination regimen (ArginMax) could provide a major impact in support of male sexual function. First, a review of the supporting literature.

It is well established that nitric oxide (NO) is the key mediator for the up-regulation of cGMP which in turn mediates erectile function.(1) L-arginine is the precursor of nitric oxide. The conversion of L-arginine to nitric oxide is mediated by nitric oxide synthase (NOS). Increasing tissue L-arginine levels results in the increase of NO and cGMP.(2,3) Supplementation with L-arginine has been shown to be sufficient to restore endothelial-d erived nitric oxide production in many disorders in which endothelial-derived nitric oxide is reduced or impaired including impairment resulting from diabetes and hypercholesterolemia.(4,5,6,7,8) Studies also point to the role of L-arginine as not only a substrate for NOS in the up-regulation of cGMP, but also acts to reduce cell-mediated breakdown of nitric oxide.(9) The efficacy of Korean ginseng (Panax Ginseng) in treating erectile dysfunction was recently demonstrated in a randomized controlled clinical trial involving a total of 90 patients studied over 3 months, 30 each receiving placebo, trazadone, or ginseng.(10) Ginseng was the most efficacious treatment with improvements measured in erectile parameters such as girth, libido, and patient satisfaction. Frequency of intercourse, ejaculations, and erections did not differ among groups. In a controlled study with 66 patients, Panax ginseng was demonstrated to increase spermatozoa count and motility, testosterone, DHT, FSH, and LH levels in 66 patie nts with fertility problems.(11) Ginsenosides (the primary active component of ginseng) have been shown to increase NO production in endothelial cells.(12,13,14) One observed mechanism for increase in NO production is up-regulation of NOS activity by ginsenosides.(14) The effects of ginsenosides on NO production has implications for improved sexual function, and may partly account for the aphrodisiac effect of Panax ginseng used in traditional Chinese medicine.

Ginkgo biloba is well established to facilitate microvascular circulation(15) which may physiologically lead to improvement of erections. In addition to ginkgo biloba's ability to facilitate microvascular circulation, potentially benefiting erectile function through enhanced vascular blood flow, there is evidence that ginkgo biloba extract may also directly elucidate smooth muscle relaxation in the corpus cavernosum, likely via effects on the nitric oxide pathway.(16,17)

B-complex vitamins are important to the activity of hundreds of enzymes and in energy metabolism. Low levels of circulating folate and vitamin B6 confer an increased risk of peripheral vascular disease,(18) leading to potential reduction of erectile function.

Zinc is a fundamental mineral in the maintenance of human reproductive function. Low levels of serum zinc has been shown to cause sexual dysfunction and associated with infertility in males.(19,20) Zinc deficiency during growth periods result in lack of gonadal development in males.(21,22) Zinc deficiency leads to depletion of testosterone and inhibition of spermatogenesis.(23) Zinc is also thought to help extend the functional life span of ejaculated spermatozoa.(23)

Selenium has a key influence on spermatozoa numbers and motility. It is an essential element in normal spermatozoa development. Selenium is incorporated in the sperm mitochondria capsule and may thus affect the behavior and function of the spermazoon.(24) It has been shown that dietary supplementation with selenium-vitamin E statistically significantly in creases sperm motility, percent live, and percent normal spermatozoa.(25)

It is well established that one of the key roles of seminal plasma is the protection of spermatozoa against reactive oxygen species.(26) In a study of 101 patients seeking consultation for infertility and 15 fertile donors, a strong inverse relationship was found between total reactive antioxidant potential in seminal plasma and infertility.(26)

ArginMax (The Daily Wellness Company, Mt. View, CA) is a natural dietary supplement which incorporates a highly standardized combination of ginkgo biloba (24% flavone glycosides, 6% terpene lactones), Korean ginseng (Panax Ginseng-30% ginsenosides), American ginseng (Panax Quinquefolius- 5% ginsenosides), L-arginine, along with B-vitamins 6 and 12, folate, antioxidant vitamins A, C, E, thiamin, riboflavin, niacin, biotin, pantothenic acid, zinc, and selenium. ArginMax was developed as a dietary supplement to support male sexual fitness. This paper reports our findings of a clinical p ilot study of male sexual function using ArginMax as a daily dietary supplement in a group of men with mild to moderate erectile dysfunction.

Materials and Methods

We recruited male subjects with mild to moderate erectile dysfunction through various medical clinics. Interested participants were enrolled at a test center located in a urology clinic at a University of Hawaii affiliated teaching hospital (Kuakini Medical Center). Subjects were enrolled in a consecutive manner until 25 patients had been enrolled for this pilot phase of the study. All interested participants were allowed to enroll regardless of etiology of erectile dysfunction. Initial work up consisted of a detailed patient past medical history including history and etiology of erectile dysfunction, treatment and medication history, and a physical examination including blood pressure, height, and weight. The subjects were then instructed on the use and regimen of ArginMax as a dietary supplement and were requested to fill out a baseline SFQ (Sexual Function Questionnaire). Subjects started a twice-per-day regimen of ArginMax, once in the morning upon waking and once in the evening at bedtime. A 4-week supply of ArginMax was provided. After completing the 4-week regimen, patients were instructed to complete a 4-week SFQ and return to the test center for follow-up evaluation and examination.

The SFQ (Sexual Function Questionnaire) was used as the primary test instrument. The SFQ is a self-administered questionnaire beginning with the validated IIEF (International Index of Erectile Function used with permission) test instrument designed to measure changes in erectile function and sexual function.(27,28,29) Following the IIEF questions, the SFQ included questions regarding subject's activities, condition during the trial period, and quality of life. (30,31)

Results

Subject Group Profile At Baseline:

Total number of subjects - 25; Age range - 40-77; Number hypertensive- 19; Number diabetes mellitus- 4

Study Results:

Sexual Function Improvements as Measured By SFQ:

Patient responses to SFQ variables at 4 weeks were compared to SFQ responses at baseline. A comparison analysis was performed for those subjects whose degree of erectile dysfunction were mild to moderate as characterized by a minimal baseline score of 2 in comparison to their 4 week score on the same SFQ variable. The results were then pooled, summarized, and evaluated to reflect the percentage of subjects with improvement in each of the SFQ variables. The following are our findings showing the two highest and two lowest SFQ variable results:

88.9% of subjects showed improvement in the ability to maintain erection during intercourse, as measured by the following SFQ variable: Over the past 4 weeks, during sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner? 0 = Did not attempt intercourse, 1 = Almost never/never, 2 = A few times (much less than half the time), 3 = Sometimes (about half the time), 4 = Most times (much more that half the time), 5 = Almost always/always 75.0% of subjects showed improvement in satisfaction with overall sex life, as measured by the following SFQ variable: Over the past 4 weeks, how satisfied have you been with your overall sex life? 1 = Very dissatisfied, 2 = Moderately dissatisfied, 3 = About equally satisfied and dissatisfied, 4 = Moderately satisfied, 5 = Very satisfied 20.0% of subjects showed improvement in number of orgasms, as measured by the following SFQ variable: Over the past 4 weeks, when you had sexual stimulation or intercourse, how often did you ejaculate? 0 = No sexual stimulation/intercourse, 1 = Almost never/never, 2 = A few times (much less than half the time), 3 = Sometimes (about half the time), 4 = Most times (much more than half the time), 5 = Almost always/always 12.5% of subjects showed improvement in the number of times attempted intercourse, as measured by the following SFQ variable: Over the past 4 weeks, how many times have you attempted sexual intercourse? 0 = No attempts, 1 = One to two attempts, 2 = Three to four attempts, 3 = Five to six attempts, 4 = Seven to ten attempts, 5 = Eleven+ attempts

Subjects Dropped:

Of the 25 subjects enrolled, 21 were included in the scoring of the above shown results. Four (4) of the enrolled subjects were not included for the following reasons:

Loss of sex partner resulting in major change in sexual activity(1 subject). Did not complete study due to personal problems- unspecified(1 subject). Did not complete 4 week regimen in entirety (2 subjects).

Side Effects:

Blood Pressure Changes: no significant change in blood pressure. Mean blood pressure at baseline:135/82 (s.devs: 14.9/11.71). Mean blood pressure at 4-weeks:139/85 (s.devs:12.26/13.17).

No other significant side effects as noted. The following are net % of patients reporting increase or decrease of: headaches: -4.8%, nausea: -4.8%, stomach upset: -14.3%, chest pain: 0%, dizziness: 0%, vision disturbance: 0%

Discussion and Conclusion

Discussion:

The role of natural dietary supplements for sexual health is an infrequently discussed yet extremely important subject. Our pilot study preliminarily addressed the role of a combinatorial natural product for the enhancement of male sexual health. The proposed mechanism by which ArginMax improves sexual health and erectile function is through increasing smooth muscle relaxation, enhancing vascular dilatation, and improving peripheral circulation. Based on review of the literature pertaining to the ingredients in ArginMax, it is likely that ArginMax enhances the NO-cGMP pathway by providing additional substrate for NOS, up regulating NOS activity, and decreasing the cell-mediated breakdown of cGMP. On a vascular level, ArginMax likely facilitates erectile function by increasing blood vessel dilatation and microvascular circulation.

It is important to recognize that this pilot study is a part of a larger scale ongoing clinical evaluation of the health effects of ArginMax. Although designed as an open-label, pilot study, the results of the SFQ survey demonstrate significantly greater improvements in variables relating to erectile function than in non-erectile function related variables. It is reasonable to conclude that if only a placebo effect was noted, all variables would be impacted in a similar fashion. The presence of major variations among the variables leads us to believe that there is a physiological effect at play. Our pilot study indicates that an expansion of our current study to a larger population with a placebo-controlled protocol is the logical next step in exploring the sexual function benefits of ArginMax.

It is important to recognize that as Americans develop an ever increasing interest in dietary supplementation and the concept of wellness, that the role of a supplement for one of the most important biological functions of life, sexual health, be clinically evaluated. After all, if we take a calcium supplement for our bones, and an aspirin for our blood, why not consider tak ing a supplement for our sexual health?

Conclusion:

In a pilot clinical study of ArginMax (The Daily Wellness Company, Mt. View, CA), a natural daily dietary supplement developed to support male sexual fitness, significant improvements were noted in male sexual function after 21 subjects, ages 40-77, with mild to moderate erectile dysfunction, completed a 4 week regimen of ArginMax. 88.9% of the subjects experienced improvement in ability to maintain an erection during intercourse. 75.0% of the subjects experienced improvement in satisfaction with their overall sex life. There were no significant reports of side effects (headaches, nausea, stomach upset, chest pain, dizziness, vision disturbance, changes in BP). Based on the findings of this study, there appears to be strong indication that natural dietary supplementation (ArginMax) may play an important role in sexual health and erectile function.

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