For doctors & healthcare professionals

Clinical Reference — Products

Published evidence on our products — grouped by product, graded and bounded as stated in the governing source.

Last updated: October 2026 — Source: Knowledge Base (npfdocs)

Healthcare-professional notice

This section is a scientific reference for doctors, pharmacists and healthcare professionals. It is informational only and does not replace individual clinical judgment. No product result is attributed to another product; ingredient evidence is never presented as formulation evidence; and surrogate outcomes (e.g. semen parameters, HOMA) are never converted into pregnancy or cure promises.

How to read the evidence

• Product evidence: The exact marketed formulation at the studied dose in the target population
• Formulation evidence: A matching or near-matching unnamed mixture
• Ingredient evidence: A single ingredient the product contains
• Guideline: Professional recommendation / position statement

Binding rule: food supplements do not treat diseases. Surrogate outcomes (sperm motility, DFI, HOMA-IR, IIEF) must never be converted into patient outcomes (pregnancy, live birth). The studied dose is always stated beside the product dose.

By productMen with abnormal semen analysis / elevated DFI / preparing for ICSI

Proxeed Plus®

Studied reference formula — Limited–moderate (one between-group RCT + within-group trials)

Approved doctor message
"A formulation studied in men with abnormal semen analysis for up to 6 months, with reported improvement in selected parameters; pregnancy and live-birth outcomes have not been demonstrated for the product."

Studies of the product itself

Product evidenceLimitedVerified

Double-blind, randomised, placebo-controlled trial on the effect of L-carnitine and L-acetylcarnitine on sperm parameters in men with idiopathic oligoasthenozoospermia

Micic S, Lalic N, Djordjevic D, Bojanic N, Bogavac-Stanojevic N, Busetto GM, Virmani A, Agarwal A · Andrologia · 2019

Design: Randomised, double-blind, placebo-controlled (Serbia — single centre)
Sample: 175 men (125 on Proxeed Plus vs 50 on placebo) with idiopathic OAT: count ≤15 M/mL, progressive motility <32%
Dose & duration: 2 sachets/day (the marketed dose) for 6 months — measured at 3 and 6 months

Findings

Ejaculate volume 3.00→3.60 mL (p=0.020) over 6 months
Sperm DNA fragmentation index (DFI) fell 38.5%→31% (p<0.001; vs the 3-month mark p=0.014)
Progressive motility 28%→31% (p<0.001); vitality 0.52→0.56 (p=0.002)
Placebo arm unchanged; alpha-glucosidase activity and seminal carnitine improved

Limits — what it does not show

— Within-group analysis only (each arm vs its own baseline) — no formal between-group comparison
— Baseline imbalance (motility 28% vs 23%); loss to follow-up; single centre
— Pregnancy and live birth were never measured — attributing either to this study is false
— A co-author worked for the manufacturer (Sigma-Tau); funding not declared

DOI PubMed

Product evidenceModerateVerified

Effect of metabolic and antioxidant supplementation on sperm parameters in oligo-astheno-teratozoospermia, with and without varicocele: a double-blind placebo-controlled study

Busetto GM, Agarwal A, Virmani A, Antonini G, Ragonesi G, Del Giudice F, et al. · Andrologia · 2018

Design: Randomised, double-blind, placebo-controlled (Italy)
Sample: 104 men with OAT, with or without varicocele
Dose & duration: 2 sachets/day for 6 months

Findings

Significant between-group differences favouring the product: concentration (p=0.0186), total count (p=0.0117), progressive motility (p=0.0088), total motility (p=0.0120)
Normal morphology also improved; the effect held with or without varicocele
Secondary reading 🟡: pregnancies 10 vs 2 — the trial was not designed to measure pregnancy

Limits — what it does not show

— Live birth was not a measured endpoint — no pregnancy effect can be claimed
— Adverse events were noted only in the product arm (4 nausea, 3 dizziness/headache) — secondary reading
— A co-author is a manufacturer scientist; overall certainty graded low/very low in Cochrane analyses

DOI PubMed

Product evidenceLimitedVerified

Comparison of the effects of two different antioxidant combinations on sperm parameters

Yaris M, Akdogan N, Öztürk M, Bozkurt A, Karabakan M · Urologia · 2022

Design: Prospective multicentre (Turkey), active-controlled (Carniact Duo) — open-label, no placebo
Sample: 122 men with idiopathic infertility (Proxeed Plus n=60 vs Carniact Duo n=62)
Dose & duration: 2 sachets/day for 6 months

Findings

Within the Proxeed Plus arm: total count 53.86→99.58 M (p<0.001); concentration 20.94→32.31 M/mL (p<0.001)
Fast progressive motility 13.23%→22.70% (p<0.001); normal morphology 3.50%→5.71% (p=0.008)
Independent study — no manufacturer funding

Limits — what it does not show

— Between-group differences were not significant for any parameter (p>0.05) — improvement was shared by both arms
— No placebo and no blinding; spontaneous pregnancy (secondary) did not differ significantly

DOI

Product evidenceLimitedVerified

Variation of sperm parameters after metabolic and antioxidant supplementation in infertility patients with oligoasthenoteratospermia

Ben Temime R, Fahrni AC, Major AL, Feki A · Clinical Research and Trials · 2020

Design: Prospective observational cohort (Switzerland) — within-subject baseline comparison, uncontrolled
Sample: 52 infertile men with abnormal spermograms (OAT)
Dose & duration: Standard product dose (2 sachets/day), mean 3 months

Findings

Concentration improved in 55.8% of patients and progressive motility in 51.9%; normalisation in 23% and 22.1% respectively
Positive trend (Wilcoxon) without overall statistical significance across the full cohort
🟡 Pregnancy rate 30.7% (16/52) over a 15-month window (5 spontaneous + 11 assisted) — NOT attributable to the product

Limits — what it does not show

— Small sample, no control group, variable duration; pregnancy cannot be attributed to the product
— Progressive motility p=0.547 (not significant) in the overall reading

DOI

Product evidenceLimitedVerified

Comparison of 3- and 6-month outcomes of combined oral L-carnitine fumarate and acetyl-L-carnitine therapy, included in an antioxidant formulation, in patients with idiopathic infertility

Szymański M, Wandtke T, Wasilow K, Andryszczyk M, Janicki R, Domaracki P · American Journal of Men's Health · 2021

Design: Single-arm interventional cohort (Poland) — 3 vs 6 months comparison, no control arm
Sample: 78 men with idiopathic infertility and abnormal semen parameters
Dose & duration: 2 sachets/day — 3 months vs 6 months

Findings

Significant improvement in concentration, motility and DFI vs baseline at both 3 and 6 months (p<0.05), with 6 months better than 3
No improvement in morphology or ejaculate volume
Numeric reading 🟡 (unusually high averages due to selection): concentration 6.9→8.8 M/mL; progressive motility 53.8%→62.8%

Limits — what it does not show

— No randomisation and no placebo — causal efficacy over placebo cannot be established
— Pregnancy and live birth not measured

DOI

Supporting evidence (ingredient / class)

These are ingredient- or class-level studies — they do not count as proof of the finished formulation.

Ingredient evidenceLimitedVerified

Antioxidants for male subfertility (Cochrane Review)

de Ligny W, Smits RM, et al. (Cochrane) · Cochrane Database of Systematic Reviews · 2022

Design: Systematic review and meta-analysis of 67 randomised trials on antioxidant class
Sample: Men with subfertility — mixed populations
Dose & duration: Mixed doses and formulations (class level — not attributable to one product)

Findings

Live birth OR ≈1.43 (1.07–1.91) — very low certainty; clinical pregnancy OR ≈1.89 (1.45–2.47) — low certainty — not attributable to any one product
Class context: semen parameters improved in several trials including Micic and Busetto

Limits — what it does not show

— The live-birth effect disappears after excluding high risk-of-bias studies
— Class-level evidence (antioxidants) — not evidence for any one formulation
— Semen parameters must not be converted into pregnancy promises — surrogates stay surrogates

DOI Open original source

Dose in the product vs dose studied

↔ Scroll the table sideways to see every column.

Item	In the product	In the studies	Reading
Daily dose	2 sachets (L-carnitine 2000 mg + ALC 1000 mg)	The exact same dose in all five studies	Full match — rare among supplements

What this evidence does not establish

What the studies show: improved semen parameters and DFI over 3–6 months at the product dose. None of this evidence establishes an increase in pregnancy or live birth — surrogate outcomes (semen parameters, DFI, HOMA, IIEF) remain surrogates.

View product: Proxeed Plus®

By productMen needing metabolic/vascular support

Proxeed Men®

Advanced formula — No direct evidence

Approved doctor message
"An advanced formula with three carnitines plus arginine; no direct studies exist on this combination, so only nutrient-function wording is used."

Zero direct studies on this formulation — scientific communication here is compositional transparency and nutrient-function support only.

Supporting evidence (ingredient / class)

These are ingredient- or class-level studies — they do not count as proof of the finished formulation.

Ingredient evidenceLimitedVerified

Antioxidants for male subfertility (Cochrane Review)

de Ligny W, Smits RM, et al. (Cochrane) · Cochrane Database of Systematic Reviews · 2022

Design: Systematic review and meta-analysis of 67 randomised trials on antioxidant class
Sample: Men with subfertility — mixed populations
Dose & duration: Mixed doses and formulations (class level — not attributable to one product)

Findings

Live birth OR ≈1.43 (1.07–1.91) — very low certainty; clinical pregnancy OR ≈1.89 (1.45–2.47) — low certainty — not attributable to any one product
Class context: semen parameters improved in several trials including Micic and Busetto

Limits — what it does not show

— The live-birth effect disappears after excluding high risk-of-bias studies
— Class-level evidence (antioxidants) — not evidence for any one formulation
— Semen parameters must not be converted into pregnancy promises — surrogates stay surrogates

DOI Open original source

Dose in the product vs dose studied

↔ Scroll the table sideways to see every column.

Item	In the product	In the studies	Reading
Printed carnitine weights	3540/1000/504 mg per day — salt weights (1770/500/252 per sachet)	No study exists on this formulation	State as salt weights — never present as active doses

What this evidence does not establish

No study exists on the current formulation. Proxeed Plus trials concern a different base and cannot be attributed to this product. None of this evidence establishes an increase in pregnancy or live birth — surrogate outcomes (semen parameters, DFI, HOMA, IIEF) remain surrogates. Marketing names like "Tricar®" do not appear on the leaflet and are not used.

View product: Proxeed Men®

By productWomen with natural cycles / preparing for ART procedures

Proxeed Women®

Preconception support — Very limited (uncontrolled preliminary data)

Approved doctor message
"Preconception nutritional support; no controlled studies, only small uncontrolled preliminary data."

Studies of the product itself

Product evidenceLimitedPreliminary — pending paper match

Open-label study of Proxeed Women in overweight women with PCOS

Genazzani A, et al. · مذكور في سجل الدراسات — الربط الكامل بالمنشور قيد التحقق · 2020

Design: Open-label, single-arm — no comparison group (Italy)
Sample: 53 women started, 45 completed — overweight PCOS
Dose & duration: The marketed product dose (1 sachet/day) for 24 weeks

Findings

Insulin, HOMA and lipid markers improved over 24 weeks (positive trend as recorded)
Reproductive hormones, LH and weight did not change
🟡 Detailed figures sit in secondary notes not yet matched against the paper — published here descriptively, without numbers

Limits — what it does not show

— No control group — spontaneous improvement over time cannot be excluded
— Metabolic surrogate markers (HOMA/insulin) — not clinical pregnancy or ovulation outcomes
— Any pregnancy readings are confounded by pregnancy-related dropout and the missing control arm — not attributable to the product

Open original source

Product evidenceLimitedPreliminary — pending paper match

Before/after study of Proxeed Women in functional hypothalamic amenorrhoea (FHA)

Genazzani A, et al. · مذكور في سجل الدراسات — الربط الكامل بالمنشور قيد التحقق · 2020

Design: Before/after, uncontrolled (Italy); a different condition from PCOS
Sample: 29 women with functional hypothalamic amenorrhoea
Dose & duration: The marketed product dose (1 sachet/day) for 12 weeks

Findings

LH and insulin rose, cortisol and amylase fell — in the low-LH subgroup only
🟡 Detailed figures pending matching against the paper — published descriptively

Limits — what it does not show

— No control group and no pregnancy or cycle-regularity endpoint
— The condition (FHA) differs from the product's core audience — indirect evidence

Open original source

Dose in the product vs dose studied

↔ Scroll the table sideways to see every column.

Item	In the product	In the studies	Reading
Carnitines	500 + 250 mg (700 mg total)	2,000–3,000 mg in positive studies	~4× lower
NAC	50 mg	1,200–1,800 mg	~24× lower
L-arginine	500 mg	1,600 mg (and 16 g in an IVF study)	3–32× lower
Vitamin D3	200 IU	4,000 IU/day	~20× lower

What this evidence does not establish

The product contains no CoQ10 and no inositol (anything else is wrong). Preliminary data cover metabolic/hormonal markers in PCOS and FHA only. None of this evidence establishes an increase in pregnancy or live birth — surrogate outcomes (semen parameters, DFI, HOMA, IIEF) remain surrogates. Product doses sit below the doses that showed effects in the literature — the source itself acknowledges this.

View product: Proxeed Women®

By productWomen with natural cycles / preparing for ART — metabolic support in PCOS

Proxeed® Women Inositol

Preconception support — Very limited (one retrospective study)

Approved doctor message
"Preconception nutritional support; no controlled studies, only small uncontrolled preliminary data."

Studies of the product itself

Product evidenceLimitedVerified

Retrospective study of the current Proxeed Women Inositol formulation (exact product doses) in overweight women with PCOS

Genazzani A, et al. · Gynecological Endocrinology 41(1):2458710 · 2025

Design: Retrospective, no comparison group — Modena clinic records (Italy) 2022–2024
Sample: 25 overweight/obese women with PCOS
Dose & duration: The product's exact doses (including myo-inositol 1 g/day) — 12 weeks in the abstract vs 4 months in the tables

Findings

HOMA-IR 4.6→2.9 (p=0.04); insulin 19.2→13.0 (p=0.05); fasting glucose 95.2→85.7; LDL 121→95
LH 9.1→7.4 and FSH 6.3→5.1 (down); LH/FSH ratio unchanged (1.4→1.5); androgens did not improve
The authors declare no conflicts of interest

Limits — what it does not show

— Retrospective selection of completers only (dropouts missing — inflates results); no comparison group
— No clinical outcomes: no cycle regularity, ovulation, pregnancy or weight; androgens and testosterone did not improve
— Multiple uncorrected tests (p=0.04–0.05 may be chance); inconsistent duration between abstract and tables
— Product myo-inositol dose is 1 g vs 4 g in most positive studies — higher-dose results must not be attributed to the product

PubMed

Supporting evidence (ingredient / class)

These are ingredient- or class-level studies — they do not count as proof of the finished formulation.

Ingredient evidenceLimitedVerified

Inositol for women with a diagnosis of polycystic ovary syndrome and subfertility (Cochrane Review)

Cochrane Gynaecology and Fertility Group · Cochrane Database of Systematic Reviews (CD012378) · 2018

Design: Systematic review and meta-analysis — 13 randomised trials, 1,472 women
Sample: Women with PCOS and subfertility
Dose & duration: Mixed inositol doses (ingredient level — not attributable to a 1 g product)

Findings

Live birth OR 2.42 (0.75–7.83) from just two trials and 84 women — very low certainty

Limits — what it does not show

— The confidence interval includes 1 — the review cannot establish increased pregnancy or live birth
— Ingredient evidence — not attributable to any commercial formulation or dose

Open original source

Guideline positions

GuidelineStrongVerified

Position statement — Inositol in PCOS (SOGC, February 2025)

Society of Obstetricians and Gynaecologists of Canada (SOGC) · SOGC Position Statement · 2025

Design: Guideline position statement
Sample: Women with PCOS
Dose & duration: Usual studied dose 2 g twice daily (4 g/day) — higher than the product's 1 g

Findings

Myo-inositol is a possible metformin alternative for cycle regularity/ovulation — weak recommendation, moderate certainty
Studies at 4 g generally performed better; insufficient evidence for a specific dose or product

Limits — what it does not show

— No recommendation for any commercial product; no long-term safety data
— The guideline does not treat infertility as a diagnosis — first-line ovulation induction is different

Open original source

GuidelineStrongVerified

International Evidence-Based Guideline for the Assessment and Management of PCOS 2023 (JCEM 108(10):2447)

International PCOS Guideline (Teede HJ, et al.) · Journal of Clinical Endocrinology & Metabolism · 2023

Design: International evidence-based guideline
Sample: Women with PCOS
Dose & duration: No recommendation on inositol type, dose or formulation

Findings

Inositol may be considered per patient preference, with limited clinical benefit; it is regarded as experimental for infertility treatment
Letrozole remains first-line for ovulation induction

Limits — what it does not show

— Guideline context — must not be cited as efficacy evidence for any commercial supplement

Open original source

Dose in the product vs dose studied

↔ Scroll the table sideways to see every column.

Item	In the product	In the studies	Reading
Myo-inositol	1,000 mg (1 sachet/day)	4,000 mg in most positive studies	A quarter of the studied dose — 4 g results are not attributable to 1 g
Folic acid	400 µg (calcium-L-methylfolate)	Folic acid is the only form proven for neural-tube-defect prevention	Methylfolate is a compositional distinction, not a proven clinical advantage

What this evidence does not establish

The only same-dose study is retrospective and uncontrolled (25 women), covering HOMA/insulin markers only. The formulation contains no D-chiro-inositol and no 40:1 ratio — any claim otherwise is wrong. None of this evidence establishes an increase in pregnancy or live birth — surrogate outcomes (semen parameters, DFI, HOMA, IIEF) remain surrogates.

View product: Proxeed® Women Inositol

By productMen — desire/energy/sexual wellness

Proxerex®

Vascular wellness — Moderate ingredient evidence (L-arginine)

Approved doctor message
"2.5 g arginine supporting nitric-oxide production; a wellness product, not an ED treatment and not a PDE5 replacement."

Zero studies on the current formulation — the scientific signal sits entirely at the L-arginine ingredient level.

Supporting evidence (ingredient / class)

These are ingredient- or class-level studies — they do not count as proof of the finished formulation.

Ingredient evidenceModerateVerified

Network meta-analysis of nutritional supplements in male erectile dysfunction

Barbonetti A, et al. · Journal of Sexual Medicine 21(11):1054–1063 · 2024

Design: Network meta-analysis — 15 trials, ~1,000 men
Sample: Men with mild–moderate erectile dysfunction
Dose & duration: Mixed doses (including L-arginine alone 1.5–5 g)

Findings

SUCRA ranking: PLC+ALC+Sildenafil 97% · L-arginine+Tadalafil 84% · Sildenafil 79% · Tadalafil 72% · L-arginine alone 52%
A moderate arginine signal as an ingredient — stronger when added to a PDE5 drug than alone

Limits — what it does not show

— Most rankings lack direct head-to-head comparisons — ranking is not proven efficacy
— The 97% figure belongs to PLC+ALC+Sildenafil, not arginine alone — any other use of the number is wrong
— Ingredient-level evidence on the IIEF surrogate — it must not be converted into a treatment or cure claim

DOI

Guideline positions

GuidelineStrongVerified

EAU Guidelines — Sexual & Reproductive Health (2025): the role of L-arginine in mild ED

European Association of Urology (EAU) · EAU Guidelines on Sexual and Reproductive Health · 2025

Design: Professional guideline
Sample: Men with erectile dysfunction
Dose & duration: The literature uses L-arginine 1.5–5 g — the product provides 2.5 g (within range)

Findings

L-arginine: +2.74 IIEF-EF points over placebo — a change the patient may not perceive (perceptible change ≈6 points)
Weak recommendation for L-arginine only in mild ED for patients refusing drugs; first-line: PDE5 inhibitors + lifestyle change

Limits — what it does not show

— Ingredient-level guideline context — does not prove the efficacy of any commercial formulation
— ED can be an early sign of a vascular/metabolic problem — medical evaluation comes first

Open original source

Dose in the product vs dose studied

↔ Scroll the table sideways to see every column.

Item	In the product	In the studies	Reading
L-arginine	2,500 mg	1.5–5 g (10 trials / 540 patients)	Within range — the product's strongest ingredient
Carnitines (PLC + ALC)	≈250 + 125 mg	2 g + 2 g in the studies	8–16× lower
Maca	150 mg	2,400 mg (weak effect even at the high dose)	~16× lower

What this evidence does not establish

No study exists on the current formulation. Studies of the older mixture (Ezerex) concern a different product still on the market — their results must not be attributed to Proxerex or used comparatively. None of this evidence establishes an increase in pregnancy or live birth — surrogate outcomes (semen parameters, DFI, HOMA, IIEF) remain surrogates. All evidence sits on the IIEF surrogate; any phrasing suggesting an ED treatment or a PDE5-drug alternative is prohibited.

View product: Proxerex®

By productWomen — low desire / menopausal symptoms

Ellamuselle®

Female wellness — No evidence

Approved doctor message
"Zinc and niacin nutrient-function support only; no clinical studies; not intended for women trying to conceive."

Zero studies — stated plainly: this product has no direct clinical evidence.

Dose in the product vs dose studied

↔ Scroll the table sideways to see every column.

Item	In the product	In the studies	Reading
L-arginine	500 mg	~2 g in women's trials	~4× lower — and women's evidence is weak to begin with
Ginkgo	25 mg	240–300 mg (and good trials were negative)	10–12× lower
Black cohosh	40 mg	Dose is 'in range' — but evidence of benefit is insufficient	Not beyond 6 months without medical consultation

What this evidence does not establish

No clinical study exists on the product or its formulation — testimonials are not evidence. Studied single ingredients (ginkgo, black cohosh, damiana) are either negative or lack adequate trials. The product is not for women trying to conceive. None of this evidence establishes an increase in pregnancy or live birth — surrogate outcomes (semen parameters, DFI, HOMA, IIEF) remain surrogates.

View product: Ellamuselle®

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Notice: this reference is informational only and not a substitute for medical advice. Consult your doctor before making any treatment decision.