Reviews of L Arginine Plus and Pine Bark Extract
J Tradit Complement Med. 2017 Jan; 7(i): 117–120.
Effects of a supplement combining Pycnogenol® and l-arginine aspartate on lower urinary dysfunction compared with saw palmetto extract
Received 2015 Sep 28; Revised 2016 April 26; Accepted 2016 May 24.
Abstract
Objectives
Lower urinary tract symptoms (LUTS) and sexual dysfunction (SDys) are common problems that affect quality of life (QOL) in elderly men. In addition to prescribed drugs, many over-the-counter medications including supplements are used to treat QOL diseases. Phosphodiesterase inhibitors are reported to be effective for both LUTS and SDys past increasing nitric oxide levels. French maritime pine bark extract Pycnogenol®, which is a potent nitric oxide donor, is reported to be effective for SDys. Even so, no reports have been published on whether it ameliorates LUTS.
Design
Open-labeled, randomized study. The furnishings of ii supplements, Nokogiriyashi EX® containing 160 mg saw palmetto (SP) extract per tablet and Edicare® containing 10 mg of Pycnogenol®, 115 mg of fifty-arginine and 92 mg of aspartate (PAA) per tablet on International Prostate Symptom Score (IPSS), IPSS–QOL, Overactive Float Symptom Score (OABSS), International Alphabetize of Erectile Function five (IIEF5), Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), urinary 8-OHdG and uroflowmetry (UFM) of total xl men with LUTS and SDys were examined.
Results
19 subjects were instructed to take two tablets of SP, on the other 20 were on four tablets of PAA for sixteen weeks. IPSS and IPSS–QOL showed statistically meaning improvements in both groups. OABSS and IIEF5 were significantly improved in the PAA group. Conversely, ICIQ-SF, 8-OHdG and UFM did not modify in either group.
Conclusions
PAA might be an effective therapeutic alternative for elderly patients with LUTS and SDys.
Keywords: Lower urinary tract symptoms, Sexual dysfunction, Pycnogenol®, Saw palmetto, Oxidative stress
Graphical abstract
i. Introduction
The incidence of benign prostatic hyperplasia (BPH) gradually increases with age, and the disease results in both lower urinary tract syndromes (LUTS) and sexual dysfunction (SDys).one The treatment options for LUTS range from behavioral modifications, such as bladder training, to medical handling. Alpha-one blockers and 5-alpha-reductase (5AR) inhibitors are the virtually frequently prescribed drugs, but they tin can too crusade SDys.two
Preparations made from the berries of saw palmetto (SP) (Serenoa repens) accept a long history of use in the handling of LUTS and SDys.3 , 4 , 5 , vi , 7 Reported modes of action include inhibition of 5AR and anti-inflammatory activities, too as inhibition of autonomous receptors in the lower urinary tract.7 On the other hand, clinical studies take reported that the proprietary, patented combination of l-arginine aspartate and French maritime pine (Pinus pinaster) bark excerpt Pycnogenol® might improve balmy to moderate SDys.8 Pycnogenol® consists of a concentrate of polyphenols and acts to amend SDys past increasing nitric oxide production and promoting vasodilation.8 , 9 , x , 11 Yet, there is no reports on the clinical cess of supplements containing of Pycnogenol®, l-arginine, aspartic acid (PAA) for LUTS accompanied past SDys.
In the present study, we attempted to make up one's mind the efficacy and safe of a supplement containing PAA for elderly patients with both LUTS and SDys compared with a supplement containing SP extract.
ii. Materials and methods
This study was conducted in compliance with the Helsinki Proclamation subsequently approval was granted by the Ethics Commission of Dokkyo Medical University Koshigaya Hospital. Nosotros obtained written informed consent from all participants after thoroughly explaining the efficacy and possible adverse reactions of SP and PAA.
Patients who consulted our hospital with LUTS and SDys between June 2013 and May 2014 were considered for enrollment. The inclusion criteria were 1) male patients betwixt 55–80 years of historic period; two) an International Prostate Symptom Score (IPSS) of 8 or more; 3) the presence of LUTS for at least 2 months; and 4) the presence of SDys (erectile dysfunction and/or decreased libido). Exclusion criteria were one) habitual consumption of a supplement that is intended for the handling of LUTS or SDys; 2) allergy to the substances under investigation; 3) any complications that could affect voiding function such as neurogenic bladder, urethral stricture, and active urinary tract infection; 4) the existence of diabetes mellitus, center disease, renal disease, or hepatic illness. And all participants were required to visit the outpatient clinic at the starting time visit, and subsequently 4, eight and 16 weeks.
The written report was designed as an open, randomized, two-arm study comparing the commercialized food supplement Nokogiriyashi EX® (manufactured past Kobayashi Pharmaceutical Co., Ltd., and containing 160 mg SP extract per tablet) and Edicare® (manufactured past Kobayashi Pharmaceutical Co., Ltd., and containing 10 mg of Pycnogenol®, 115 mg of l-arginine, and 92 mg of aspartic acrid per tablet).
Subjects had blood and urine samples collected, were asked well-nigh their general health status and examined by a physician before the start of the report, and again at 8 and xvi weeks afterward the written report. In combination with the questioning by the physician: IPSS, IPSS-Quality of Life (QOL), the 5-item version of the International Alphabetize of Erectile Office (IIEF5), Consultation on Incontinence Questionnaire-Brusk Form (ICIQ-SF), Overactive Bladder Symptom Score (OABSS), height, body weight, BMI, uroflowmetry (UFM) and prostate estimated weight measured by abdominal ultrasonography were too recorded. Blood test parameters consisted of cerise blood cell count, white claret cell count, hemoglobin, hematocrit, platelet count, total protein, albumin, lactate dyhydrogenase (LDH), alkaline metal phosphatase (ALP), aspartate amino transferase (AST), alanine transaminase (ALT), total bilirubin, creatinine, urea nitrogen, hemoglobin Alc, triglycerides, full cholesterol, HDL cholesterol, LDL cholesterol, sodium, potassium chlorine, and serum prostaglandins. The pH, qualitative protein, qualitative glucose and occult blood were investigated by urinalysis. Equally a marker of oxidative stress, we evaluated urinary eight-OHdG levels using an ICR-001 device (Techno Medica, Yokohama, Nippon) according to the manufacturer's recommendations.
Data are reported every bit means ± SD and were analyzed using SPSS software version 12.0 (IBM, Chicago, IL). Wilcoxon signed-rank examination was used to evaluate the effects of treatment, and P < 0.05 was considered significant.
3. Results
3.1. Patients
Forty subjects were instructed to take two tablets of Nokogiriyashi EX® (SP 320 mg/twenty-four hour period) or 6 tablets of Edicare® (Pycnogenol® lx mg/day) for 16 weeks. 1 subject in the SP grouping was unable to keep the study because of an adverse reaction (loose stool) and was excluded from the analysis. Thus, xix subjects (age range 68–80 years, mean 76.vii ± 6.9) in the SP grouping and 20 subjects (age range 67–80 years, mean 76.1 ± iv.vii) in the PAA group (Tabular array ane) were examined. There were no significant differences in clinical parameters betwixt the 2 groups.
Table i
Backgrounds of participants.
| SP | PAA | p-value | |
|---|---|---|---|
| Age (years) | 76.7 ± vi.ix | 76.1 ± iv.vii | 0.142 |
| Height (cm) | 168.3 ± 3.6 | 167.ii ± 4.9 | 0.177 |
| Body weight (kg) | 69.i ± viii.9 | 68.3 ± six.ix | 0.467 |
| BMI (kg/m2) | 23.8 ± 2.vii | 24.9 ± 2.3 | 0.267 |
| P-EW (cc) | 29.2 ± 8.four | 31.1 ± 9.8 | 0.423 |
| IPSS | |||
| Total | 13.4 ± 5.5 | 14.5 ± 6.2 | 0.182 |
| Storage | vi.2 ± two.5 | 8.1 ± 2.9 | 0.114 |
| Voiding | seven.3 ± 4.3 | viii.4 ± 4.3 | 0.974 |
| QOL | iv.0 ± 1.ane | four.0 ± 0.9 | 0.228 |
| OABSS | four.ix ± ii.5 | 6.eight ± 3.three | 0.706 |
| IIEF5 | ane.two ± 0.v | i.4 ± 0.five | 0.453 |
| ICIQ-SF | 1.nine ± 3.two | 5.3 ± four.9 | 0.197 |
| UFM | |||
| RV (ml) | 30.8 ± 22.3 | 36.4 ± 21.5 | 0.655 |
| Qmax (ml/due south) | xiii.3 ± 6.8 | 12.6 ± 6.7 | 0.187 |
| 8-OHdG (ng/mlCRE) | 18.iv ± 8.ii | 17.iv ± 5.4 | 0.725 |
3.ii. Efficancy
We found the following results in the SP grouping: 1) subjective outcomes assessed by IPSS full, subscore (storage and voiding score) and QOL were significantly improved; 2) no significant improvements were observed in the other parameters (OABSS, IIEF5, ICIQ-SF, UFM and eight-OHdG). On the other mitt, the PAA grouping showed the post-obit results: 1) subjective outcomes assessed by IPSS total, subscore (storage and voiding score), QOL, OABSS and IIEF5 were significantly improved; 2) no meaning improvements were observed in the other parameters (ICIQ-SF, UFM and 8-OHdG) (Tabular array ii). Comparing PAA to SP group showed a meaning difference regarding change from baseline of IIEF5 (Table 3). The other parameters (IPSS total, subscore, QOL, OABSS, ICIQ-SF, UFM and viii-OHdG) did not show a significant difference between the two groups.
Table 2
Effects of SP and PAA.
| SP baseline | After 16 weeks | PAA baseline | Afterwards 16 weeks | |
|---|---|---|---|---|
| IPSS | ||||
| Total | 13.four ± 5.5 | 9.6 ± 5.3 | 14.five ± 6.2 | 10.4 ± five.6 |
| Storage | vi.2 ± 2.5 | iv.4 ± two.6 | 8.1 ± 2.9 | 4.4 ± 2.6 |
| Voiding | seven.3 ± 4.three | 5.ii ± 4.1 | 8.4 ± 4.3 | 5.two ± 4.1 |
| QOL | 4.0 ± 1.ane | 2.9 ± 1.3 | 4.0 ± 0.ix | 2.9 ± 1.three |
| OABSS | 4.9 ± 2.5 | iii.9 ± ii.9 | six.eight ± 3.3 | three.9 ± 2.ix |
| IIEF5 | 1.two ± 0.5 | ane.4 ± 0.5 | ane.4 ± 0.five | 2.iii ± 1.iv |
| ICIQ-SF | ane.9 ± 3.2 | 1.6 ± ii.seven | 5.3 ± 4.ix | 2.9 ± three.8 |
| UFM | ||||
| RV (ml) | 30.8 ± 22.3 | 41.9 ± 43.ii | 36.4 ± 21.v | 41.9 ± 43.2 |
| Qmax (ml/south) | thirteen.3 ± six.eight | 12.3 ± v.three | 12.vi ± 6.vii | 12.3 ± 5.3 |
| viii-OHdG (ng/mlCRE) | eighteen.4 ± 8.two | 22.5 ± 20.8 | 17.4 ± 5.iv | 18.9 ± five.four |
Table 3
Modify from baseline.
| SP | PAA | p-value | |
|---|---|---|---|
| IPSS | |||
| Total | −3.8 ± 5.3 | −6.1 ± 4.viii | 0.536 |
| Storage | −one.7 ± 2.6 | −3.ane ± two.6 | 0.414 |
| Voiding | −2.1 ± 3.8 | −2.vii ± 3.0 | 0.804 |
| QOL | −0.eight ± 1.4 | −0.nine ± 1.6 | 0.805 |
| OABSS | −one.2 ± 2.vi | −ane.ix ± 2.8 | 0.724 |
| IIEF5 | 0.2 ± 0.5 | 0.ix ± 1.1 | 0.047 |
| ICIQ-SF | −0.nine ± 3.viii | −2.four ± 4.7 | 0.564 |
| UFM | |||
| RV (ml) | 0.5 ± 44.0 | −1.4 ± 31.ane | 0.892 |
| Qmax (ml/south) | −1.0 ± 5.three | −0.3 ± 7.0 | 0.703 |
| 8-OHdG (ng/mlCRE) | −one.0 ± 5.4 | ii.3 ± 5.seven | 0.232 |
3.iii. Blood and urine test
The baseline hateful red blood prison cell count, white blood cell count, hemoglobin, hematocrit, platelet count were all within normal limits in both groups. At the end of the xvi weeks study period, the difference of haematology results were not statistically different (data not shown). Results of biochemistry markers indicated a slight subtract in AST and HbA1c in the PAA group (data not shown), simply these changes were all within normal limits. Urinalysis remained unchanged in both group at 8 and 16 weeks.
three.4. Safty
Three patients reported 4 adverse events, including nausea, loose stool and pruritus, all of which were mild in nature and seen as related to the study medication. From the total of xl patients, one from the SP group was unable to go on the written report because of loose stool and was excluded from the analysis.
4. Discussion
In the present study, nosotros demonstrated that consumption of a supplement of PAA combination taken for 16 weeks improved both LUTS and SDys. Pycnogenol® reportedly improves erectile dysfunction (ED) by activating endothelial nitric oxide synthase (eNOS).eight Increases of nitric oxide are achieved when Pycnogenol® is administered in combination with l-arginine, the substrate for eNOS, which is suggested to be a physiological response secondary to increased sexual activity.9 The rationale for Pycnogenol® dosage was inferred from a like study of Aoki et al (2012) that used a similar PAA, we refered like study of study of similar PAA combination with Pycnogenol® 60 mg, which demonstrated a significant improvement of ED.11 However, results of improvement in IIEF5 was smaller in comparing with other reports on the effects of Pycnogenol®.x , 11 , 12 This could be partially attributed to the smaller dose of Pycnogenol® used in this study compared with other studies. The clinical trial that reported successful treatment with PAA involved 40 men between 25 and 45 years of age suffering from mild ED.10 After treatment with ane.vii g 50-arginine per mean solar day for i month, just five% of all patients experienced normal erections. During a second month of handling, fourscore mg Pycnogenol® per day was added to the arginine regimen and yielded a meaning improvement, with 80% of patients showing normal erections. A third calendar month's treatment with l-arginine, together with an increased corporeality of Pycnogenol® (120 mg per day), further increased the number of patients with restored normal erectile function. At the end of the trial, 37 patients, equivalent to 92.5% of all participants, achieved normal erectile part. Moreover, the other reason for the smaller comeback in IIEF5 was because of the mean age of patients in that report. Patients were in their fifties compared to the mean age of 76.1 years in the nowadays study.13
The results of this study showed that consumption of a supplement of SP significantly improved IPSS full, subscore of storage and voiding, IPSS-QOL. SP have a long standing utilise in the treatment of mild to moderate LUTS and ED.iii , four , 5 , 6 , 7 More than than thirty controlled clinical trials evaluating treatments for LUTS and SDys accept demonstrated long-term efficacy.5 , 6 , 7 The found, which is indigenous to Florida, was offset used by white settlers in the U.s.a. non only for treatment of LUTS but also a handling for ED, to improve testicular cloudburst and sperm production.iii , 4 Regarding the mode of action, a variety of mechanisms for SP have been proposed including anti-androgenic effects (prevention against the body's natural response to testosterone by inhibition of the 5AR), anti-inflammatory and anti-proliferative effects, but none have been conclusively proven.7 In a 2002 Cochrane meta-assay of the efficiency of SP extracts for men with LUTS attributed to BPH, 21 clinical trials were identified. Compared to placebo, SP significantly reduced nocturia, increased self-rated improvement, and improved meridian uroflow.14 Adverse effects were exceptional. All the same, results comparison PAA to SP group in this study demonstrated that change from baseline of IIEF5 was significantly improved in the PAA group.
Oxidative stress is reported to consequence in pathophysiological weather condition of the urinary bladder past damaging the urothelium and sensitizing float afferent signaling.xv Previous studies have shown that oxidative stress mediates capsaicin-sensitive c-fibers to induce bladder hyperactivity.sixteen Several investigators have shown that Pycnogenol® enhances antioxidant systems and scavenges free radicals.17 , 18 Therefore, nosotros hypothesized that Pycnogenol® might ameliorate pathophysiological atmospheric condition in the urinary bladder and could be a possible therapy for cases of LUTS that are unresponsive to α1-blockers or antimuscarinic drugsnineteen , 20 However, nosotros did not demonstrate the anti-oxidative furnishings of either supplement in this study.
The major limitations of this written report were the pocket-sized number of patients, lack of a placebo group, and the omission of urodynamic data. The comeback of LUTS and SDys has a strong placebo component, so the possibility of a placebo effect might exist high. It remains unclear whether a supplement containing PAA might be a potential therapeutic culling for elderly patients with LUTS and SDys; therefore, a prospective placebo-controlled written report should exist conducted in the about hereafter.
five. Conclusions
Edicare®, a supplement containing PAA might be an effective potential therapeutic alternative for elderly patients with LUTS and SDys. However, farther clinical investigations past placebo control studies are required to elucidate the precise mechanisms of this supplement.
Conflict of interest
None alleged.
Author disclosure statement
No competing fiscal interests exist.
Acknowledgements
Edicare® and Nokogiriyashi EX® were provided past Kobayashi Pharmaceutical Co., Ltd. This study was partially supported by the grant from Kobayashi Pharmaceutical Co., Ltd.
Footnotes
Peer review under responsibleness of The Heart for Food and Biomolecules, National Taiwan University.
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