Clinical & Scientific Data

Saw Palmetto

Tier 2 supplement containing fatty acids and beta-sitosterols commonly used to help men with prostate or urinary symptoms.

• Shown in vivo to reduce the weight and inhibit growth of prostate (rat)6.
• Clinically shown to be comparable or more effective than pharmaceutical drugs for pain and urinary symptoms associated with prostatitis and BPH7,8,23.
• May help reduce the pressure that the prostate exerts on the urethra by shrinking the lining of the prostate9.
• Reduce cancer cell proliferation and inflammation10,11. Beta-sitosterols have been shown clinically to decrease levels of DHT (hormone linked to BPH) and significantly improve urinary flow 12,13.

Saw Palmetto Clinical Studies*

Design Population Dosage/ Duration N Results
Double-blind, randomized, placebo-controlled trial14 LUTS 6 months 85 • Saw palmetto led to a statistically significant improvement in urinary symptoms in men with LUTS compared with placebo.
Randomized15 Chronic prostatitis Grp A:160 mg 2 x D
Grp B: 0.4 mg Tamsulosin
6 weeks
157 • Similar progress in CPSI scores
• Group A: larger decline in pain scores without negative sexual side effects associated with tamsulosin.
Double Blind, Randomized comaprative16 Moderate BPH Saw palmetto or finasteride (5mg)
6 months
1098 • Saw palmetto inhibited 5-α-reductase
• Effect similar to finastride without side effects associated with drug
Open label17 BPH related UT symptoms 320 mg
2 years
120 • Improved IPPS (5.5 points), QoL, Qmax, IIEF and decrease in residual urinary amount (urinary obstruction).
• Prostate vol decreased from mean 39.8 ml to 36 ml.
Open Label , multi center, Pilot Study BPH 320 mg
8 weeks
82 • IPSS reduces by 51%
• Improved sexual function

Saw Palmetto Clinical Results - BPH




Suter, Andreas, R Saller, et al. Improving BPH symptoms and sexual
dysfunctions with saw palmetto preparation. Results from a pilot trial. Phytother. Res. Feb 2013.

Beta-Sitosterol Clinical Results




Berges RR, Windeler J, Trampisch HJ, Senge T. Randomised, placebo-controlled, double-blind
clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Lancet. 1995 Jun 17;345(8964):1529-32.

Stinging Nettle

Herb commonly used to treat urinary problems associated with BPH and urinary tract infections.

• Clinically shown to relieve difficulty in urinating and urge to urinate caused by BPH18,20,21.
• In vitro seen to interfere with SHGB and prevent it from combining with androgens19.
• Ability to act as a 5-α-reductase inhibitor, preventing the conversion of testosterone to Dihydrotestosterone (DHT)22.
• German Commission E approves the use of nettle leaf as supportive therapy in patients with LUTS (combined with immune and antimicrobial therapy) and to prevent and treat formation of urinary gravel.

Stinging Nettle Clinical Studies*

Design Population Dosage/ Duration N Results
Prospective,randomizeddouble blind, placebo controlled cross over21 BPH 120 mg
3 x D for 6 months
558 Significant reduction in IPSS, serum PSA and prostate size
Randomized, double blind, placebo controlled109 BPH 300 mg
2 x D for 8 weeks
100 Treatment group had better effect in relieving clinical symptoms in BPH patients compared to placebo

Stinging Nettle Clinical Results - BPH




Ghorbanibirgani A, Khalili A, Zamani L. The Efficacy of Stinging Nettle (Urtica Dioica) in Patients with Benign Prostatic Hyperplasia:
A Randomized Double-Blind Study in 100 Patients. Iran Red Cres Med J. 2013;15(1):9-10

Combination Therapy Clinical Studies*
(Saw Palmetto with Stinging Nettle or Quercetin)


Design Population Dosage/ Duration N Results
Prospective20 LUTS secondary to BPH Stinging nettle /saw palmetto /pinus pinaster (120/320/5 mg) alone or w/ antibiotics or α- blockers 3 m-1yr 320 Reduced the symptoms in 85% of the patients in treatment group
Prospective, randomized , double blind, double dummy, multicenter, comparative23 LUTS caused by BPH Stinging nettle /Saw palmetto (120/160 mg) vs. Tamsulosin 60 weeks 140 IPSS improvement Both groups 9 pts QOL improved 2 points (1 pt tamulosin)
Randomized, double blind, placebo controlled22 LUTS caused by BPH Stinging nettle/Saw palmetto (120/160 mg) vs. placebo 24 wks & 24 wks open 257 Stinging nettle/saw palmetto group was clearly superior to the placebo for the amelioration of LUTS as measured by the I-PSS
Prospective, randomized7 Prostatitis Grp 1: Antibiotics, saw palmetto, quercetin & other natural ingredients Grp 2: Antibiotics 143 Group 1:
• ~90% reported symptoms were gone after 1 month (27% on antibiotics alone)
• 6 months follow up: no re occurrence

Stinging Nettle and Saw Palmetto
Combined (PRO) Clinical Efficacy IPSS




Lopatkin N, et al Long-term efficacy and safety of a combination of sabal and urtica extract
for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial . World J Urol. (2005)

Quercetin

Tier 1 supplement and natural occurring flavonoid recognized as a potent antioxidant, anti-inflammatory and relief of symptoms associated with prostatitis.

• Promoted prostate cancer cells apoptosis and caspase activation in vitro 27,28,31, 32
• Shown in vivo to work with finasteride to reduce prostate weight24 and anti-tumor activity 30.
• Clinically shown to provide symptomatic improvement in CP/CPPS and shown to enhance the efficacy of antibiotic to treat CP when used un combination with other natural ingredients (saw palmetto and stinging nettle) 7.
• A recommended treatment though the UPOINT System for Prostatitis Treatment used by medical professionals 25,26.

Quercetin Clinical Studies*

Design Population Dosage/ Duration N Results
Randomized double blind, placebo controlled29 CP/CPPS Grp A: 500 mg 2 x D
Grp B: Placebo
1 month
28 Decrease in IPPS:
Grp A: from 21.0 to 13.1
Grp B from 20.2 to 18.8
Improvement in symptoms:
Grp A: 67%
Grp B: 25% by 20% of patents
Follow up, unblinded, open label29 CP/CPPS 500 mg quercetin combination supplement (bromelain and papain for absorption) 17 82% had 25% improvement in symptoms “Significant symptomatic improvement”
Multimodal, Chronic Prostatitis Symptom Index (CPSI)25 CP/CPPS Multi modal based on UPOINT phenotype 26 weeks 100 Quercetin associated with greater CPSI decrease
Prospective, randomized7 CP Grp A:Quercetin, cumin, saw palmetto, stinging nettle & prulifloxacin
Grp B:Prulifoxacin /14 D
143 Symptoms of prostatitis
Grp A: none /Grp B: 27%
Recurrence following 6 months
Grp A: none /Grp B: 2 patients

Quercetin Effect on human prostate tumors




Yang, F., Jiang, X., Song, L., Wang, H., Mei, Z., Xu, Z., Xing, N."Quercetin inhibits angiogenesis through
thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo". Oncology Reports 35.3 (2016): 1602-1610.

Quercetin Inhibition on prostate cancer cells




Yang, F., Jiang, X., Song, L., Wang, H., Mei, Z., Xu, Z., Xing, N."Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize
human prostate cancer PC-3 cell growth in vitro and in vivo". Oncology Reports 35.3 (2016): 1602-1610.

Quercetin Clinical Results



Pygeum Africanum

Tier 2 herb used to promote prostate and bladder health, BPH, and nocturia reduction.

• Major active components are fat-soluble sterols (phytosterols) and fatty acids that can inhibit the production of DHT (dihydrotestosterone), pro-inflammatory prostaglandins in the prostate48,49.
• Contains triterpenes and ferulic acid nesters to block the accumulation of cholesterol in the prostate49.
• Shown in vitro and in vivo to modulate bladder contractility, inhibit cancer cell proliferation and viability, promote cell apoptosis, and suppress production of prostaglandins41-46.
• Clinically shown to improve urinary flow, reduce nocturia, and improve prostate symptoms in men with BPH or prostatitis33-37,47.

Pygeum Africanum Clinical Studies*

Design Population Dosage/ Duration N Results
Placebo-controlled, double blind, multi center36 Micturitional disorders due to BPH 100 mg/ D
60 D
263 Improved:
• Mictrition 66% (31% placebo grp)
• Uinary max. flow 17.2%
• Overall: 50%
Increased voided volume 12%
• Decreased:
• Nocturia 31% and daytime freq 19.4%
Parallel grp, double blind, comparative phase35 BPH GGrp A 50 mg: 2/D
Grp B 100 mg/1 D
Open phase:
100 mg 1 D/ 10 m
209 Improved:
• Avg IPSS Grp A 38% /Grp B 35%
• Qol 28%
• Max urinary Grp A 16% /Grp B 19%
Open label37 BPH Tandenan (Pygeum extract) 85 Improved:
• IPPS 40% /QOL 32% /Nocturia 32%
Statistically significant urinary flow and vol.
Open label33 Chronic prostatitis 100 mg/d for 5-7wks 47 89% reported complete remission of symptoms
Open label34 Sexual disturbance due to BPH or chronic prostatitis 200 mg/d for 60 days 18 Improved all urinary parameters and sexual function

Pygeum Africanum (PA) Effect on prostate
stromal cells from patients with BPH




MT Quiles et al. Antiproliferative and Apoptotic Effects of the Herbal Agent Pygeum Africanum on
Cultured Prostate Stromal Cells From Patients With Benign Prostatic Hyperplasia (BPH) . Prostate 70 (10), 1044-1053. 2010 Jul 01

Pygeum Africanum
Clinical Result - BPH




Wilt T, Ishani A, Mac Donald R, Rutks I, Stark G. Pygeum africanum for benign prostatic hyperplasia.
Cochrane Database Syst Rev. 2002;(1):CD001044 (latest version in 16 Nov 2001).

Green Tea Extract

Tier 2 supplement with antioxidant qualities to provide support for prostate health, normal prostate size, and anti-cancer protective effect.

• Shown to regulate DHT production and hormones that influence prostate volume. Catechins (polyphenol compounds) in green tea shown to have anti-inflammatory qualities, reduce infection, enhance the immune system, and regulate the production and activities of hormones50,51.
• In vitro, in vivo and clinical studies identified EGCG (green tea catechin) to be a modulator of molecular pathways to prostate carcinogenesis52,53.
• In vitro EGCG acts as an anti-androgen antagonist, suppresses prostate cancer cell proliferation and production of prostate-specific antigen (PSA), reduces tumor size and delays development of prostate tumors (TRAMP mice)54-56.
• Clinically shown in randomized trails to reduce overall rate of progression of prostate cancer in men with HGPIN57-59.

Green Tea Clinical Studies*

Design Population Dosage/ Duration N Results
Single center, randomized, placebo controlled58 HGPIN 600mg GTC /daily
12 months
60 90% reduction in prostate cancer
Multicenter, randomized (US), Placebo controlled57 HGPIN or atypical small acinar proliferation Polyphenon E, 200mg) 2X / D / 12 m 97 Decreased rate of progression to atypical sm acinar proliferation or prostate cancer in men with HGPIN
Open label, Ph II, randomized60 Prostate cancer, pre radical prostatectomy 6 cups green tea, black tea, or water 113 Significant decrease in PSA levels (P=.04) in green tea group
Open label, Ph II61 Prostate cancer, pre radical prostatectomy 4 cups Polyphenon E tablets (tea polyphenols,w 800 mg EGCG) daily until surgery 26 Positive effect on number of prostate cancer biomarker, including VEGF and IGF-1
Random , placebo controlled62 Prostate cancer, pre radical prostatectomy Polyphenon E tablets 800 mg EGCG) 1xD / 3-6 w 50 Greater decrease in serum levels of PSA and IGF-1 than placebo group

Green Tea Clinical Effect




Saverio Bettuzzi et al. Cancer Res 2006;66:1234-1240

Lycopene

Carotentoid produced by plants - enhances antioxidant response to support prostate health, generally recognized as safe (GRAS).

• Epidemiological /Clinical studies link increased lycopene consumption with decreased prostate cancer risk, decreasing serum PSA levels, suppression of tumor growth and supporting urinary function63-69,75.
• Animal studies show antitumorigenic effect73-74.
• In vitro and in vivo shown to enhance the antioxidant response of prostate cells, inhibit proliferation, demonstrate chemopreventive effect induce apoptosis and decrease the metastatic capacity of prostate cancer cells 70, 71.
• May affect insulin-like growth factor (IGF) intracellular pathway in prostate cancer cells70.

Lycopene Clinical Studies*

Design Population Dosage/ Duration N Results
Randomized controlled78 High risk intraepithelial neoplasia 4 mg 2 x/D 1 yr
2 yr follow up
40 Incident of prostate cancer:
• 10% intervention grp/ 30% control grp
PSA decrease from 6.07 to 3.5 ng/ml/ (increased in control group)
Randomized controlled77 BPH 15 mg
1 x D for 6 months
40 Significant PSA reduction in intervention grp /not in control grp
Prostate enlargement in control but not intervention grp
Randomized controlled72 Prostate cancer 15 mg
2XD for 3 weeks
26 PSA serum
• Intervention grp decrease 18%
• Control group increase 14%
Microscopically free resection margins
• Intervention grp: 73%
• Control grp 18%
Randomized controlled76 Prostate cancer, cancer metastases and orhidectomy 2 mg
2 xD for 24-28 months
54 PSA serum levels:
• Intervention grp sig lower (p<0.001)
• Survival rate:
Intervention grp sig higher (p(0.001)
Urinary peak flow:
• Intervention grp sig higher (=0.04)

Lycopene




Holsapfel N, B Holzapfel, S Champ, et al. The potential role of lycopene for the prevention and
therapy of prostate cancer: from molecular mechanisms to clinical evidence, In J Mol Sci. 2014. 14, 14620-46.

Essential Vitamins and Minerals
Vitamin E and Selenium (Mineral)

Vitamin E and selenium have antioxidative properties and are widely used to prevent damage to the cells, tumor suppression in prostate cancer and provide immune support.

• Shown in vitro and in vivo to reduce risk of prostate cancer, suppress tumor progression and cell apoptosis87,90-92.
• Selenium has shown in vitro to decrease the activity of the androgen receptor leading to apoptosis and growth inhibition on prostate cancer cells, increase levels of p53 (tumor suppression) and regulate oxidative and the immune system88,89.
• Higher blood selenium concentrations have been clinically associated with decreased prostate cancer (EPIC and Physicians’ health study) and decrease PSA levels81-84

Vitamin E and Selenium Clinical Studies*

Design Population Dosage/ Duration N Results
‘ATBC’ randomized placebo controlled79 Male smokers age 50-68 Grp 1: 50iu Vit E
Grp 2: Vit E & Beta Carotene
Grp 3: Beta Carotene
Grp 4: Placebo
1 x/day for 5-8 years
29,133 Grp 1 and 2: reduced incidence of prostate cancer by 32%
Grp 1: 41% fewer deaths for prostate cancer
Measure blood and prostatic tissue selenium levels80 Grp A: PC
Grp B: BPH
Grp C: Healthy Men
None 66 Blood levels of selenium were significantly lower in PC compared to Healthy men
Randomize, placebo controlled85 Healthy men Grp 1: 200 mcg
Grp 2: Placebo
6 weeks
60 • Grp 1 reduced levels of PSA (Grp 2 no change)
• Significant increase levels of erythrocyte and plasma glutathione peroxidase in Grp 1 compared to 2.
Meta analyses of 12 studies86 Mixed 13, 254 Inverse relationship between blood/serum level of selenium and PC

Lycopene and Vitamin E
Effect on prostate cancer cells




Jacqueline Limpens et al. J. Nutr. 2006;136:1287-1293

Essential Vitamins and Minerals
Vitamin B6, Vitamin D and Zinc

Vitamins and mineral required for proper prostate function, cell repair and immune health.

Vitamin B6 - Recognized for the proper manufacture and metabolism of hormones necessary for prostate health.


Zinc - Tier 3 supplement for prostatitis, prostate cancer and BPH.
• Induced apoptosis and antiproliferative effect on PC and BPH cells in vitro94,95.
• Plays a role in testosterone, sperm formation /mobility, and DNA damage repair 106, 107.
• Clinical experience associates inverse relationship between zinc intake and risk of prostate issues94-96,99,101.


Zinc
Relationship between Zinc intake and PC




Mahmoud, Abeer M. et al. “Zinc Intake and Risk of Prostate Cancer: Case-Control Study and Meta-Analysis.” Ed. Aamir Ahmad. PLoS ONE 11.11 (2016): e0165956. PMC. Web. 19 Apr. 2017.