Every Free Life Labs formula lists named ingredients at stated doses. This page gathers the published research on each ingredient, sorted strongest-evidence first and linked to PubMed, so you can review it before you dispense or recommend.
Summaries of published ingredient research for clinician reference; not product trials unless stated.
Dietary supplement · 2 capsules daily (1 capsule twice daily with food)
Formulated with 600 mg alpha-lipoic acid and 300 mg benfotiamine per day, plus methylated B vitamins in active forms and vitamin D3. Clinical doses, named forms, no proprietary blend. Made in an FDA-registered, cGMP facility and third-party tested.
181 patients with diabetic polyneuropathy took ALA 600, 1,200 or 1,800 mg or placebo once daily for 5 weeks. Total Symptom Score fell by 51%, 48% and 52% vs 32% on placebo. Nausea, vomiting and vertigo rose with dose, and the authors judged 600 mg once daily the best risk-to-benefit dose.
460 patients with mild-to-moderate DSPN, randomized. The primary composite end point did not differ. NIS and NIS-LL impairment scores favored ALA, with more patients improving and fewer progressing. Serious adverse events were 38.1% vs 28.0% on placebo.
90 people with type 2 diabetes on long-term metformin and B12 <400 pmol/L. B12 rose to ~777 pmol/L, and nerve conduction, VPT, sudomotor function, pain and QoL improved vs placebo. Autonomic reflex tests did not change significantly.
214 patients with type 2 diabetes, randomized for 24 weeks, took a combination at 3 mg / 2 mg / 35 mg. VPT (primary end point) did not change. NTSS-6 symptom scores improved at weeks 16 and 24, and homocysteine fell 2.7 µmol/L vs a 0.5 rise on placebo.
Doses, routes and durations are taken from each study’s PubMed abstract. Where a study used a different dose, form or route, the comparison is shown as-is.
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT SYDNEY 2 RCT | 600 / 1,200 / 1,800 mg oral | 5 weeks | All doses beat placebo; 600 mg = best risk-benefit |
| RCT NATHAN 1 RCT | 600 mg oral | 4 years | Primary end point n.s.; impairment scores favored ALA |
| Meta-analysis Meta-analysis (4 RCTs) | 600 mg IV | 3 weeks | Symptoms and deficits improved |
| RCT ALADIN III RCT | 600 mg IV → 1,800 mg oral | 3 wk + 6 mo | No meaningful symptom effect; deficits favored ALA |
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT BENDIP RCT | 300 or 600 mg | 6 weeks | NSS improved (per-protocol); more at 600 mg |
| RCT BEDIP pilot RCT | 400 mg | 3 weeks | Neuropathy score improved vs placebo |
| RCT Fraser RCT (type 1) | 300 mg | 24 months | No effect on nerve function |
| RCT Winkler randomized open | 150 mg; 320 mg (with B-vitamins) | 6 weeks | Greatest change at the higher dose |
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT Didangelos RCT | 1,000 µg methylcobalamin | 12 months | Nerve conduction, pain, QoL improved |
| RCT Mansour RCT | 1,000 vs 2,000 µg B12 | 16 weeks | Similar symptom benefit; 2,000 µg added none |
| RCT Fonseca RCT (combo) | 2 mg methylcobalamin | 24 weeks | Symptoms improved; VPT unchanged |
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT Fonseca RCT (combo) | 3 mg L-methylfolate · 35 mg P-5-P | 24 weeks | NTSS-6 improved; homocysteine fell |
| Clinical study Walker open-label | 3 mg · 35 mg (twice daily × 4 wk, then once daily) | 1 year | Cutaneous sensitivity improved |
| RCT Levin RCT (B6 alone) | Pyridoxine HCl 150 mg | 4 months | Similar to placebo |
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT Karonova RCT | 5,000 vs 40,000 IU/week | 24 weeks | Benefits at 40,000/week only |
| Clinical study Basit open-label | 600,000 IU single IM dose | 20 weeks | Pain scores fell |
| Clinical study Shehab trial | Oral D3 once weekly | 8 weeks | NSS improved; NDS and NCS unchanged |
An antioxidant studied in research on sensory discomfort tied to diabetic nerve challenges, and for oxidative stress around nerves.
Mechanism studied: Antioxidant; reviews attribute its effects in DSPN to lower oxidative stress and better microcirculation. Hsieh 2023
Strongest study designs first · top 3 shown
Meta-analysis Meta-analysis of 4 RCTs (n=1,258): 600 mg/day IV ALA for 3 weeks in symptomatic diabetic polyneuropathy.
Meta-analysis Meta-analysis of 10 RCTs (1,242 patients) of oral ALA: favorable for Total Symptom Score (dose-related trend), NDS and global satisfaction; not for VAS, VPT, NIS-LL or nerve conduction.
Meta-analysis Meta-analysis of RCTs: IV ALA 600 mg/day for 3 weeks gave a significant, clinically relevant reduction in neuropathic pain; whether oral >600 mg/day for 3–5 weeks is clinically relevant was unclear.
Meta-analysis Systematic review/meta-analysis: IV ALA 300–600 mg/day for 2–4 weeks improved nerve conduction velocity and positive symptoms; most included studies were of poor methodological quality.
Systematic review Cochrane systematic review: ALA probably has little or no effect on neuropathy symptoms or adverse events at six months; all included studies at high risk of attrition bias.
RCT NATHAN 1 RCT (n=460, 4 years): oral ALA 600 mg/day did not change the primary composite end point; neuropathic-impairment scores (NIS, NIS-LL) favored ALA. Serious adverse events 38.1% vs 28.0% on placebo.
RCT SYDNEY 2 RCT (n=181, 5 weeks): oral ALA 600, 1,200 or 1,800 mg once daily each improved Total Symptom Score vs placebo (−51%, −48%, −52% vs −32%); authors judged 600 mg once daily the best risk-to-benefit dose.
RCT ALADIN III RCT (n=509): 3 weeks IV then 6 months oral ALA had no clinically meaningful effect on symptoms vs placebo, with a favorable effect on neuropathic deficits.
RCT RCT (n=40, 2 weeks): methylcobalamin and ALA both reduced neuropathy scores; ALA reduced burning and pain more, methylcobalamin slightly more for numbness and paresthesia.
RCT RCT (chemotherapy-induced neuropathy): oral ALA did not prevent oxaliplatin/cisplatin neurotoxicity; high attrition limited feasibility.
RCT ISLAND RCT: lipoic acid 300 mg/day improved endothelial function and inflammation markers in metabolic syndrome.
RCT SYDNEY RCT: IV ALA rapidly improved positive neuropathic sensory symptoms such as pain.
RCT DEKAN RCT: 800 mg/day oral ALA for 4 months in cardiac autonomic neuropathy (heart-rate variability) in type 2 diabetes.
RCT ALADIN RCT (3 weeks IV): ALA 600 mg/day was superior to placebo for symptoms; adverse events were more frequent at 1,200 mg (32.6%) than 600 mg (18.2%).
Animal study Animal study: ALA and nerve conduction / endoneurial blood flow in diabetic rats.
A fat-soluble form of B1 (a thiamine prodrug) studied for higher bioavailability than standard thiamine: in a pharmacokinetic study, oral benfotiamine produced much higher plasma thiamine bioavailability than thiamine hydrochloride. Trials have used 150–600 mg/day, with mixed results over longer follow-up.
Mechanism studied: Lipid-soluble thiamine prodrug with higher bioavailability than thiamine HCl. In diabetic rats it inhibited nerve AGE formation (animal data). Xie 2014Stracke 2001
Strongest study designs first · top 3 shown
Meta-analysis Review and meta-analysis: B-vitamin supplementation may improve some neuropathy scores and sural nerve function in DPN; pain and motor-nerve effects inconsistent; heterogeneity precludes firm recommendations.
Systematic review Cochrane review (vitamin B for peripheral neuropathy): limited randomised data, insufficient to determine benefit or harm; one small alcoholic-neuropathy trial favored oral benfotiamine for vibration threshold over 8 weeks.
RCT 24-month RCT in type 1 diabetes (n=67): benfotiamine 300 mg/day raised blood thiamine but had no significant effect on peripheral nerve function or inflammatory markers.
RCT BENDIP RCT (165 randomised, 6 weeks): benfotiamine 300 or 600 mg/day; Neuropathy Symptom Score improved in the per-protocol population (ITT p=0.055), more at the higher dose; Total Symptom Score did not differ.
RCT BEDIP 3-week randomized pilot (n=40): benfotiamine 400 mg/day improved the neuropathy score vs placebo (p=0.029), most for pain; vibration (tuning-fork) test unchanged.
RCT Study on different benfotiamine dosage regimens in diabetic neuropathy research.
RCT 12-month phase II RCT in type 2 diabetes with mild-to-moderate symptomatic DSPN: benfotiamine was well tolerated but had no significant effect on morphometric, neurophysiological or clinical neuropathy measures.
RCT Phase I single- and multiple-ascending-dose study in healthy subjects: benfotiamine was safe and well tolerated.
RCT Pharmacokinetic study: oral benfotiamine gave much higher plasma thiamine (~1,147%) and erythrocyte TDP (~196%) bioavailability than thiamine hydrochloride.
RCT BAP I RCT: benfotiamine studied in alcoholic polyneuropathy over 8 weeks.
RCT Benfotiamine–vitamin B combination studied in diabetic polyneuropathy research.
Clinical study Benfotiamine studied in diabetic polyneuropathy research.
Animal study Benfotiamine’s pharmacological profile vs thiamine disulfides.
Animal study Animal study (diabetic rats): benfotiamine, but not thiamine, improved nerve function measures and inhibited neural AGE formation.
An active form of B12. Observational studies and trials link diabetes and long-term metformin use to lower B12 status, and B12 deficiency is associated with neuropathy measures.
Mechanism studied: Cofactor for homocysteine remethylation to methionine; proposed nerve mechanisms include myelination, nerve regeneration and reduced ectopic firing. Selhub 1999Julian 2020
Strongest study designs first · top 3 shown
Meta-analysis Systematic review/meta-analysis of RCTs: mecobalamin in combination may improve clinical efficacy and nerve conduction; evidence for mecobalamin alone is not clear.
Meta-analysis Meta-analysis of 31 studies: metformin associated with lower B12 and higher risk of deficiency (RR 2.09), dose- and duration-dependent; no significant association with anemia or neuropathy prevalence.
Meta-analysis Systematic review/meta-analysis of 6 RCTs: metformin lowered serum B12 vs comparators, with a larger drop at ≥2,000 mg/day.
Systematic review Systematic review (24 articles): some evidence for B12 in post-herpetic neuralgia (level II) and painful peripheral neuropathy (level III).
RCT RCT in DPN with low serum B12: 16 weeks of 1,000 µg or 2,000 µg/day oral B12 improved neuropathic symptoms similarly; 2,000 µg added no further neuropathic benefit.
RCT 1-year RCT (n=90, type 2 diabetes on metformin ≥4 years, B12 <400 pmol/L): oral methylcobalamin 1 mg/day raised B12 and improved nerve conduction, VPT, sudomotor function, pain and QoL; autonomic tests and MNSIE did not improve significantly.
RCT Multicenter RCT (24 weeks): acetyl-L-carnitine was as effective as methylcobalamin (the active comparator) on symptoms and neurophysiology in DPN.
RCT DPP/DPPOS secondary analysis of an RCT: long-term metformin use was associated with biochemical B12 deficiency and anemia.
RCT RCT (n=390 on insulin, 4.3 years): metformin 850 mg three times daily lowered B12 by 19% vs placebo and raised the absolute risk of B12 deficiency by 7.2 points; authors link the deficiency to raised homocysteine.
RCT Double-blind study: methylcobalamin improved somatic and autonomic symptoms in diabetic neuropathy; nerve conduction did not change at 4 months.
Observational B12/folate deficiency linked to higher homocysteine and oxidative stress.
Observational Functional B12 deficiency (high MMA) was common in older adults with diabetes; neuropathy was present in 62% with high MMA vs 18% with normal MMA, and B12 therapy improved MMA in 88%.
Observational Metformin use was associated with lower B12, higher MMA/homocysteine, and more severe neuropathy measures.
Not in PubMed 24-week study using 1500 mcg methylcobalamin daily.
L-methylfolate (5-MTHF) is the active form of folate the body uses directly and its main circulating form; it is not folic acid. The MTHFR enzyme makes 5-MTHF, and common MTHFR variants (C677T, A1298C) have been linked to reduced enzyme activity, which reduces the ability to make 5-MTHF. Supplemental 5-MTHF is already past that step. See the methylation deep-dive below.
Mechanism studied: 5-MTHF is the predominant circulating folate and the carbon donor for remethylating homocysteine to methionine. Frosst 1995
Strongest study designs first · top 3 shown
RCT Multicenter RCT (n=214, 24 weeks): L-methylfolate 3 mg + methylcobalamin 2 mg + P-5-P 35 mg did not change VPT (primary end point) but improved NTSS-6 symptom scores at weeks 16 and 24 and lowered homocysteine (−2.7 vs +0.5 µmol/L).
RCT RCT in older adults (n=40, 4 weeks): 400 µg/day folic acid or equimolar [6S]-5-MTHF both lowered homocysteine (−13.4% vs −7.8%; difference not significant).
RCT MTHF raises plasma folate better than folic acid in MTHFR variants.
RCT Low-dose L-MTHF equals or beats folic acid for lowering homocysteine.
Clinical study Folic acid handling by the human gut.
Observational Cross-sectional analysis in hypertensive adults: serum 5-MTHF was inversely associated with homocysteine at ≤10 ng/mL, and the association was modified by MTHFR C677T genotype.
Observational 5-MTHF + methylcobalamin + P-5-P studied in diabetic peripheral neuropathy research.
Review Narrative review of preclinical and clinical data on L-methylfolate (in a combination B-vitamin medical food) in DPN, including MTHFR C677T literature.
Review Folate, folic acid, and 5-MTHF are not the same.
Animal study Animal study (ZDF rats): the L-methylfolate/P-5-P/methylcobalamin combination at a human-equivalent dose improved sensory nerve conduction, hypoalgesia and intraepidermal nerve fiber density.
B6 already in its active form. With methyl-B12 and L-methylfolate, it’s the trio studied in small-fiber nerve research.
Mechanism studied: Pyridoxal-5′-phosphate is the cofactor for transsulfuration of homocysteine to cystathionine. Very high B6 intakes are linked to neuropathy. Selhub 1999Muhamad 2023
Strongest study designs first · top 3 shown
Meta-analysis Systematic review/meta-analysis (46 observational, 7 interventional studies): neuropathy associated with lower B12 and higher MMA and homocysteine; pooled B-vitamin treatment effects were non-significant.
Systematic review Systematic review: evidence supports a neurotoxic role of B6 at high levels; low B6 may also be a risk factor—dose context for B6.
RCT Multicenter RCT (n=214, 24 weeks): the combination with P-5-P 35 mg improved NTSS-6 symptom scores (VPT unchanged); improvement was inversely related to baseline PLP.
RCT Double-blind RCT (n=18, 4 months): pyridoxine 50 mg three times daily gave symptom relief at a similar rate to placebo (6/9 vs 4/9); nerve conduction unchanged.
RCT Study on thiamine and pyridoxine in diabetic peripheral neuropathy research.
Clinical study That combination studied for cutaneous sensitivity in diabetic neuropathy research.
Clinical study L-methylfolate + methylcobalamin + P-5-P in diabetic small-fiber nerve research.
Review Review of proposed mechanisms of pyridoxine (B6)-induced peripheral neuropathy—safety context for high-dose B6.
Research found 81% of people with neuropathy were vitamin D deficient, versus 60% without. High-dose D3 has been studied alongside diabetic nerve discomfort.
Mechanism studied: Observational meta-analyses link low 25(OH)D with DPN. One RCT reported microcirculation and inflammatory-marker changes at 40,000 IU/week. Yammine 2022Karonova 2020
Strongest study designs first · top 3 shown
Meta-analysis Meta-analysis of RCTs (4 trials, n=320): vitamin D reduced short-term pain in painful diabetic neuropathy vs placebo (SMD −0.85); small, variable-quality trials, so authors call for larger RCTs before routine use.
Meta-analysis Meta-analysis: vitamin D deficiency was more prevalent in diabetic patients with neuropathy (pooled OR 1.84 fixed-effects; 2.87 random-effects).
Meta-analysis Systematic review/meta-analysis: lower 25(OH)D was associated with type 2 DPN; more high-quality research needed.
Meta-analysis Systematic review/meta-analysis: vitamin D deficiency is very likely associated with DPN in type 2 diabetes; further validation needed.
Systematic review Systematic review: vitamin D supplementation could add value in painful DPN; pain improvement may relate to the vitamin D level attained.
RCT RCT (n=67, 24 weeks): cholecalciferol 40,000 IU/week improved neuropathy scores, cutaneous microcirculation and IL-6/IL-10; no changes with 5,000 IU/week.
Clinical study High-dose vitamin D studied alongside diabetic neuropathy discomfort.
Clinical study Vitamin D3 supplementation studied in neuropathy research.
Observational 81% with neuropathy were vitamin D deficient vs 60% without in one study.
Observational NHANES 2001–2004 analysis (n=591 adults with diabetes): vitamin D insufficiency and peripheral neuropathy.
Research letter Type 2 diabetics had lower pain scores after 3 months of vitamin D.
Why the formula uses L-methylfolate, methylcobalamin and P-5-P, and what published studies do and do not show. Each statement summarizes a PubMed abstract and links to it.
Meta-analysis Association between neuropathy and B-vitamins: A systematic review and meta-analysis
Meta-analysis Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis
Meta-analysis Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis
Meta-analysis Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis
Meta-analysis Metformin Treatment and Homocysteine: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Meta-analysis Elevated serum homocysteine level in the development of diabetic peripheral neuropathy
RCT Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial
RCT Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces serum homocysteine concentrations in older adults
RCT Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial
RCT [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C-->T polymorphism of methylenetetrahydrofolate reductase
RCT Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study
RCT Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial
Clinical study Improvement of cutaneous sensitivity in diabetic peripheral neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate
Clinical study Folic acid handling by the human gut: implications for food fortification and supplementation
Clinical study Management of diabetic small-fiber neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate
Observational Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin
Observational Nutritional management of patients with diabetic peripheral neuropathy with L-methylfolate-methylcobalamin-pyridoxal-5-phosphate: results of a real-world patient experience trial
Observational Association of MTHFR gene C677T mutation with diabetic peripheral neuropathy and diabetic retinopathy
Observational Plasma homocysteine levels are independently associated with the severity of peripheral polyneuropathy in type 2 diabetic subjects
Observational Association of homocysteine with peripheral neuropathy in Chinese patients with type 2 diabetes
Observational Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy
Observational Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus
Observational Increasing homocysteine levels and diabetic autonomic neuropathy
Genetic / lab study A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity
Genetic / lab study A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?
Genetic / lab study A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase
Review Folate, folic acid and 5-methyltetrahydrofolate are not the same thing
Review Homocysteine metabolism
Review The metabolism of homocysteine: pathways and regulation
Animal study Metanx alleviates multiple manifestations of peripheral neuropathy and increases intraepidermal nerve fiber density in Zucker diabetic fatty rats
For clinician reference. These associations come from the cited studies. They are not a basis for diagnosis, and this panel does not recommend genetic testing. NerveReverse Formula is a dietary supplement; the research above is ingredient research, not trials of this formula.
Other ingredients: microcrystalline cellulose, vegetable cellulose (capsule), magnesium stearate, silicon dioxide.
Topical analgesic · 4% menthol (active) · apply up to 3–4 times daily
A cooling topical analgesic for temporary relief of minor aches and pains, with 4% menthol up front and MSM, alpha-lipoic acid, and L-arginine as supporting ingredients. For external use only.
Regulatory status: FDA-registered OTC drug, made under FDA's OTC monograph for external analgesics, in an FDA-registered cGMP facility.
60 breast-cancer patients on chemotherapy, randomized: 1% menthol on the hands and feet twice daily vs standard care. CIPN symptoms improved more over 6 weeks with menthol.
51 patients with cancer treatment-related neuropathic pain (mostly CIPN) applied 1% menthol cream twice daily. At 4–6 weeks, 82% of evaluable patients (31/38) had improved Brief Pain Inventory scores. Uncontrolled.
Menthol selectively activates TRPM8 channels. As a counter-irritant it cools, then desensitizes nociceptors, and may engage central analgesic pathways. High concentrations may cause cold allodynia.
Doses, routes and durations are taken from each study’s PubMed abstract. Where a study used a different dose, form or route, the comparison is shown as-is.
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT Ozdemir RCT (CIPN) | 1%, twice daily | 6 weeks | CIPN symptoms improved vs standard care |
| Clinical study Fallon open study | 1% cream, twice daily | 4–6 weeks | 82% improved BPI (uncontrolled) |
| RCT Johar randomized (DOMS) | 3.5% gel | Single session | Less discomfort than ice |
| RCT Dillon RCT (blood flow) | 5% gel | Single session | Skin blood flow ↑ at site |
| RCT Lasanen randomized | 0.5% / 4.6% / 10% gel | Single session | 4.6% felt coolest; cooling similar |
| Clinical study Makibuchi (healthy) | 10% solution | Single session | Lower pain-evoked potentials |
The cooling topical analgesic. Research has looked at topical menthol in nerve-related discomfort and musculoskeletal pain, including its action on the TRPM8 cold receptor.
Mechanism studied: Selective TRPM8 activator. Topically it acts as a counter-irritant that cools, then desensitizes nociceptors; it is also vasoactive. Pergolizzi 2018Dillon 2022
Strongest study designs first · top 3 shown
RCT RCT of topical menthol for chemotherapy-related neuropathy symptoms.
RCT Randomized crossover study (n=15 healthy adults): 5% menthol gel increased skin blood flow at the treated site and modestly across the dermatome, consistent with TRPM8 activation.
RCT Randomized study (n=10 healthy men): 0.5%, 4.6% and 10% menthol gels all cooled the skin; concentration did not change skin cooling, but 4.6% felt coolest.
RCT Randomized study (n=16, delayed-onset muscle soreness): 3.5% menthol gel reduced perceived discomfort more than ice and allowed greater evoked force.
RCT RCT: a menthol-based topical analgesic reduced pain sensitivity (pressure-pain threshold) similarly whether applied to the upper or lower body.
RCT Randomized human study: topical menthol dose-dependently increased cutaneous blood flow; sensory-nerve inhibition attenuated the effect.
RCT Triple-blind RCT: topical menthol vs placebo for chronic arm/hand pain.
Clinical study L-menthol and pain-related somatosensory-evoked potentials.
Clinical study Proof-of-concept: topical 1% menthol cream in treatment-related neuropathic pain.
Clinical study 3.5% topical menthol gel studied in knee osteoarthritis functional tasks.
Observational Retrospective chart review (n=21, refractory localized neuropathic pain, 71% chemotherapy-induced): menthol cream titrated 1%→10%; 12/21 met the responder criterion at 10%. Exploratory.
Review Role and mechanism of menthol in topical analgesic products.
Review Review of menthol’s role in pain and analgesia, including TRPM8.
Most MSM research is oral — knee comfort, physical function, and quality of life. Cited here as ingredient research, not a claim that this cream treats arthritis.
Strongest study designs first · top 3 shown
Meta-analysis Meta-analysis of DMSO and MSM in osteoarthritis of the knee.
RCT RCT: MSM and knee quality of life in people with mild knee pain.
RCT Randomized controlled study of MSM supplementation in knee osteoarthritis.
An antioxidant researched (mostly orally or IV) for sensory findings, neuropathic symptoms, and idiopathic pain — ingredient research, not a claim that this cream treats disease.
Strongest study designs first · top 3 shown
Meta-analysis Meta-analysis of 4 RCTs (n=1,258): 600 mg/day IV ALA for 3 weeks in symptomatic diabetic polyneuropathy.
RCT SYDNEY 2: oral ALA in symptomatic diabetic polyneuropathy.
RCT RCT of oral ALA for pain of unknown etiology (not a disease-treatment claim for this cream).
RCT Sensory findings studied with ALA in diabetic polyneuropathy research.
RCT DEKAN RCT: 800 mg/day oral ALA for 4 months in cardiac autonomic neuropathy (heart-rate variability) in type 2 diabetes.
RCT ALADIN: 3-week multicenter RCT of IV alpha-lipoic acid in symptomatic diabetic polyneuropathy.
Nitric-oxide precursor. A small topical pilot looked at blood flow and temperature in the feet; a 12-patient pain study gave L-arginine by IV infusion (not by mouth or topically); a 3-month placebo-controlled RCT (3 g three times daily) found no microcirculation or neuropathy effect. Ingredient background, not trials of this cream.
Mechanism studied: Substrate for nitric-oxide synthesis (L-arginine/NO pathway). Figueroa 2017
Strongest study designs first
RCT Placebo-controlled L-arginine RCT (n=30, 3 g three times daily, 3 months, neuropathic diabetic foot): no effect on endothelial function, TcPO₂, NDS or VPT.
Clinical study Transdermal L-arginine cream: temperature and blood flow in the feet (pilot).
Clinical study IV L-arginine infusion (30 g) and pain scores in 12 patients with persistent pain.
Active ingredient: 4% menthol. Other ingredients: MSM, alpha-lipoic acid, L-arginine. Avoid eyes, mucous membranes, and broken skin. Discontinue if irritation occurs.
Topical cream · 42% urea · once daily · includes pumice stone + brush
42% urea up front, with mango and shea butters and humectants behind it. Urea is part of the skin’s natural moisturizing factor (NMF); at high concentration it is researched as both a humectant and a keratolytic for thick, dry skin such as heels.
Randomized, double-blind, bilateral comparison in 25 adults with moderate-to-severe xerosis. At day 14, 40% urea was superior for most measures, including roughness, fissures, thickness and dryness.
167 people with diabetes and a deep heel fissure were randomized for 4 weeks. Complete healing was 46.3% vs 33.3% (p=0.088). Fewer deep open fissures remained (6.4% vs 24.1%), and xerosis improved.
Split-foot double-blind RCT, 40 patients, 4 weeks: 10% urea + 4% lactic acid vs vehicle. Xerosis improved more on the urea side, and the difference held 2 weeks after stopping.
Doses, routes and durations are taken from each study’s PubMed abstract. Where a study used a different dose, form or route, the comparison is shown as-is.
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT Ademola RCT (xerosis) | 40% cream | 14–28 days | Superior to 12% ammonium lactate at day 14 |
| RCT Ross RCT (heel fissures) | 40% (comparator) | 28 days | Barrier cream ≈ urea 40% |
| RCT Lahfa RCT (nails) | 40% ointment, occluded | — | Chemical nail avulsion |
| RCT Syed RCT (nails) | 20% (+2% butenafine) | — | Keratinolysis adjunct |
| RCT Pham RCT (diabetic feet) | 10% (+4% lactic acid) | 4 weeks | Xerosis improved vs vehicle |
| RCT Federici RCT (diabetic feet) | 5% (+arginine, carnosine) | — | Hydration improved |
Urea is a small, water-loving molecule the skin already makes as part of natural moisturizing factor (NMF); dry, thickened skin often runs low on it. At high concentrations, topical urea is researched as both a humectant (pulls and holds water) and a keratolytic (helps loosen hard keratin so thick, dry skin can soften). Ingredient research, not a claim that Derm 42 treats a disease.
Mechanism studied: Part of the skin’s natural moisturizing factor: a moisturizer at ≤10% and keratolytic above 10%. It also enhances penetration. Celleno 2018Pan 2013
Strongest study designs first · top 3 shown
Meta-analysis Systematic review/meta-analysis of RCTs (diabetic foot xerosis): functional creams, primarily urea-containing, outperformed standard bases.
Meta-analysis Meta-analysis of RCTs: urea cream and celecoxib both helped prevent hand-foot syndrome/skin reaction from cancer therapy; urea especially for moderate-to-severe sorafenib reactions.
Systematic review Parker et al. 2017 — systematic review of moisturisers for foot xerosis; urea was the most researched ingredient (14 studies). The review could not rank one ingredient over another due to study quality.
Systematic review Pan et al. 2013 — urea: a comprehensive review of the clinical literature (systematic review).
RCT RCT (JAPMA 2025) — double-blind, 48 enrolled, 28 days: 40% urea was the comparator for pedal (heel) fissures; a barrier-repair cream showed minimal statistical difference from urea 40%. Ingredient research, not a Derm 42 outcome claim.
RCT Multicenter RCT (n=167 with diabetes and heel fissures, 4 weeks): a urea/glycerine/petrolatum cream improved fissure closure and xerosis; complete target-fissure healing 46.3% vs 33.3% (primary end point p=0.088).
RCT Multicenter RCT (onychomycosis): 40% urea ointment under occlusion outperformed bifonazole-urea for complete chemical removal of the infected nail.
RCT RCT (type 2 diabetes, severe foot xerosis): 5% urea + arginine + carnosine cream increased skin hydration vs a glycerol-based emollient.
RCT Ademola et al. 2002 — RCT: 40% urea cream vs 12% ammonium lactate for xerosis; day 14 urea superior on roughness, fissures, thickness, and dryness.
RCT Split-foot RCT (n=40 with diabetes, 4 weeks): 10% urea + 4% lactic acid cream reduced foot xerosis more than its vehicle, with benefit persisting 2 weeks after stopping.
RCT Double-blind RCT (toenail onychomycosis): 2% butenafine with 20% urea for keratinolysis; well tolerated.
RCT Double-blind RCT (diabetic foot syndrome): two 10% urea creams of different cost both improved foot skin quality.
RCT Federici et al. 2015 — RCT: urea-containing cream vs glycerol emollient for severe foot xerosis in type 2 diabetes (urea combo, not 42%). Greater hydration with the urea cream.
RCT Open-label RCT (n=871, sorafenib): 10% urea cream three times daily lowered 12-week hand-foot skin reaction incidence (56.0% vs 73.6%) and delayed onset.
RCT Phase III placebo-controlled RCT: a urea/lactic-acid keratolytic cream did not prevent capecitabine hand-foot syndrome (null result).
RCT Gloor et al. 2002 — urea / ammonium lactate combinations studied for skin hydration and protection vs either component alone.
RCT RCT in atopic dermatitis: glycerine and urea moisturizers differed in their effects on skin barrier function.
Clinical study Clinical analysis (onychomycosis): once-weekly 40% urea/1% bifonazole under occlusion was associated with nail removal about 1 week earlier.
Clinical study Clinical report: urea nail lacquer allowed easy removal of the affected part of fungal nail plates.
Clinical study Gloor et al. 2001 — 40% urea was keratolytic in a standardized stratum-corneum test (high-dose urea NRF formulations).
Review Piquero-Casals et al. 2021 — urea in dermatology: emollient, moisturizing, keratolytic, barrier, and antimicrobial roles (review).
Review Starace et al. 2020 — clinical evidence for high-concentration urea on hyperkeratotic skin (keratolytic, moisturizing, emollient).
Review Celleno 2018 — topical urea in skincare review: lower doses moisturize; higher concentrations (>10%) exert keratolytic action.
Review Loden 2003 — review of emollients and moisturizers for dry-skin barrier; urea-containing moisturizers studied for TEWL and irritation resistance.
Unrefined mango (Mangifera indica) and shea (Butyrospermum parkii) butters — emollients that help seal moisture after urea softens thick, dry skin. Cited as ingredient research, not a claim that Derm 42 treats eczema or any disease.
Strongest study designs first
Clinical study Hon et al. 2015 — cream containing shea butter extract studied for skin hydration and acceptability (pediatric eczema; not a Derm 42 disease-treatment claim).
Aloe vera gel juice, glycerin, and tocopheryl acetate support the cream’s moisturizing feel. Glycerin is a classic humectant used in topical skincare.
Strongest study designs first
Review Fluhr et al. 2008 — glycerol and the skin: review of hydration, barrier, and related functions.
Review Loden 2003 — moisturizers with humectants (including urea) studied for dry-skin barrier function; relevant background for glycerin’s humectant role.
Pumice: after the cream has softened dead skin, gently buff — never on open, bleeding, or infected cracks.
Dietary supplement · 90 capsules · 3 capsules daily
Nutritional support for surgery and recovery — plastic surgery, orthopedic cases, and everyday recovery. Twenty ingredients across vitamins, minerals, collagen, amino acids, botanicals, and probiotics. Made in an FDA-registered, cGMP facility and third-party tested.
200 malnourished adults with pressure ulcers, randomized for 8 weeks. The enriched oral formula reduced ulcer area by 60.9% vs 45.2% on an isocaloric, isonitrogenous control.
A small double-blind RCT (n=16). Healing at 8 weeks was median 100% with vitamin C vs −14% on placebo, and half of participants were vitamin C deficient at baseline.
48 patients randomized to 170 µg or 20 µg D3 daily. Ulcers healed in 70% vs 35% (intention-to-treat). WoundWorx provides 25 µg.
Across trials of nutritional interventions for pressure ulcers, benefits are uncertain and may not differ from standard nutrition. That is why we show nulls alongside positive trials.
Reviews of surgical nutrition describe a stress cascade after surgery or injury — higher glucagon and cortisol, inflammatory cytokines, burned glycogen, and amino acids pulled from muscle to feed gluconeogenesis, immune work, and tissue repair. Micronutrient demand (vitamin C, zinc, and others) rises with it; the overdrive can run for hours to days and, after bigger operations, may linger for 2–4 weeks. WoundWorx is designed as nutritional support for that documented metabolic demand: taken for about a month before surgery to build reserves, then continued on the same 3-capsule routine alongside the clinician’s plan.
Meta-analysis Systematic review/meta-analysis (cancer patients): high-protein oral nutritional supplements associated with fewer complications and shorter stay; no effect on readmission or mortality.
Meta-analysis Systematic review/meta-analysis: perioperative immunonutrition reduced total and infectious complications after head-and-neck or GI cancer surgery.
Meta-analysis Systematic review/meta-analysis of 178 RCTs: immunonutrition, inspiratory muscle training and multimodal prehabilitation reduced hospital stay; overall evidence certainty low.
Meta-analysis Meta-analysis (major abdominal surgery): immunonutrition did not alter mortality; reduced complications and hospital stay (low-to-moderate GRADE).
Review Review: pre- and post-surgical nutrition, the surgical stress response, and preservation of muscle mass, strength and function.
Doses, routes and durations are taken from each study’s PubMed abstract. Where a study used a different dose, form or route, the comparison is shown as-is.
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT Gunton RCT (foot ulcers) | 500 mg slow-release | 8 weeks | Healing improved |
| RCT Pisalsitsakul RCT (dental) | 600 or 1,500 mg/day | 10 days | 600 mg improved early healing, pain |
| RCT Desneves RCT (pressure ulcers) | 500 mg + arginine 9 g + zinc 30 mg | 3 weeks | PUSH improved (combination) |
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT Momen-Heravi RCT (DFU) | 50 mg elemental | 12 weeks | Ulcer size reduced |
| RCT Desneves RCT | 30 mg (combination) | 3 weeks | PUSH improved (combination) |
| Study | Dose / route studied | Duration | Abstract finding |
|---|---|---|---|
| RCT Halschou-Jensen RCT (DFU) | 170 µg vs 20 µg/day | 48 weeks | 70% vs 35% healed |
| RCT Razzaghi RCT (DFU) | 50,000 IU every 2 weeks | 12 weeks | Ulcer dimensions reduced |
Fat-soluble vitamin used in epithelial tissue maintenance.
Strongest study designs first
RCT CABG RCT: vitamin A (with zinc status considered) associated with shorter ICU/hospital stays; not this dose or product, nutritional-support context only.
Clinical study Cardiac surgery patients: 5,000 IU vitamin A/day linked to lower oxidative-stress markers when zinc was adequate; not WoundWorx dose/form and not a wound-healing trial.
Collagen-synthesis cofactor — featured in wound-nutrition reviews.
Mechanism studied: Involved in every phase of wound healing, including collagen synthesis, maturation and secretion. Moores 2013
Strongest study designs first · top 3 shown
Meta-analysis Cochrane review: benefits of nutritional interventions for pressure-ulcer prevention and treatment are uncertain; there may be little or no difference vs standard nutrition.
Systematic review Wound-nutrition review
RCT Split-mouth double-blind RCT (n=42, tooth extraction): vitamin C 600 mg/day for 10 days improved early wound-size reduction and pain vs placebo.
RCT Double-blind RCT (n=16, chronic foot ulcers): 500 mg slow-release vitamin C; 8-week healing median 100% vs −14% on placebo; half had baseline deficiency.
RCT Small RCT (n=16, pressure ulcers, 3 weeks): supplements with arginine 9 g, vitamin C 500 mg and zinc 30 mg improved PUSH scores; the other arms did not.
RCT Multicenter RCT (pressure ulcers): ascorbic acid supplementation did not improve healing vs control (null result).
Review Collagen cofactor / wound-nutrition reviews
Cholecalciferol for everyday vitamin D status during recovery.
Strongest study designs first · top 3 shown
Meta-analysis Systematic review/meta-analysis (1,115 patients): lower vitamin D in diabetic foot ulcers; severe deficiency associated with higher DFU risk (OR 3.22).
Systematic review 2024 RCT review: no clear benefit of vitamin D supplementation on postoperative survival or length of stay—mixed/null signal for routine peri-op D.
Systematic review Systematic review: low vitamin D status often associated with worse post-surgical outcomes; association ≠ proof this supplement heals surgical wounds.
RCT DFU RCT: high-dose D3 (170 µg) vs low-dose improved ulcer healing rates; chronic diabetic ulcers, not elective surgery, and far above this product’s 25 µg.
RCT RCT (n=60, grade 3 DFU, 12 weeks): 50,000 IU vitamin D every 2 weeks reduced ulcer length, width and depth and improved glycemic and lipid markers vs placebo.
d-alpha-tocopherol succinate — antioxidant vitamin support.
Strongest study designs first
RCT CABG RCT of high-dose vitamin E+zinc combo shortened hospital stay/inflammation markers; combo and doses differ from this bottle—not wound-healing proof.
Review Evidence-based review: significant dearth of robust human data that vitamin E improves wound healing.
Review Perioperative review notes vitamin E may increase bleeding tendency via platelet effects; discuss with surgeon—mixed/safety-relevant literature.
Active folate form — not folic acid.
Strongest study designs first
Observational Retrospective DFU cohort used high-dose folic acid 5 mg/day—not L-methylfolate and not this product dose; exploratory nutritional context only.
Animal study Rabbit wound model: active folate (5-methyltetrahydrofolate) increased wound DNA synthesis; animal data only.
Active B12 for methylation pathways.
Strongest study designs first
Systematic review Case review: N2O anesthesia can unmask B12 deficiency with neurologic injury—supports adequacy of B12 status around surgery, not wound-cure claims for this capsule.
Supports normal cellular energy metabolism.
Strongest study designs first
RCT RCT after periodontal flap surgery used a full B-complex including 50 µg biotin—not biotin alone or this product; attachment-level gains, not systemic surgical wound proof.
Oxygen transport mineral in a familiar iron salt form.
Strongest study designs first
Meta-analysis Cochrane review of preoperative iron for anemia: evidence limited; transfusion reduction not clearly proven—nutritional correction framing, not wound-healing claims.
RCT IVICA RCT: oral ferrous sulphate raised Hb less than IV iron; transfusion rates similar—relevant to oral iron support for anemia, not this bottle treating wounds.
Chelated zinc — researched for roles in tissue repair and immune function.
Mechanism studied: Zinc deficiency delays wound healing; the benefit of supplementation is debated. Kogan 2017
Strongest study designs first · top 3 shown
Meta-analysis Meta-analysis of clinical zinc trials suggests possible ulcer-healing benefit with moderate-certainty evidence; not this chelate form/dose and not a treat/cure claim.
Meta-analysis Cochrane review: oral zinc sulphate did not appear to aid healing of arterial or venous leg ulcers; small studies with unclear risk of bias.
Systematic review Systematic review: oral nutritional supplements may enhance chronic-wound healing; high-calorie, high-protein formulas with antioxidants favored.
RCT RCT (n=60, grade 3 diabetic foot ulcer, 12 weeks): 50 mg elemental zinc/day reduced ulcer length and width and improved glycemic and oxidative-stress markers vs placebo.
RCT CABG RCT of perioperative zinc+vitamin E (high loading doses) reduced inflammation/LOS; combination study—not isolated zinc at 20 mg or wound-closure proof.
Review Zinc physiology in wound healing
L-Selenomethionine antioxidant mineral.
Strongest study designs first
Meta-analysis Cardiac-surgery selenium meta-analysis: mixed—shorter stay/CRP but no clear cut in major complications/infections; not oral selenomethionine 100 µg or wound proof.
RCT Large RCT: high-dose IV sodium selenite did not reduce organ dysfunction or mortality after cardiac surgery—null result for routine high-dose selenium.
Case report Single case: correcting zinc+selenium deficiency after RYGB coincided with laparotomy-wound improvement—n=1, combined micronutrients, not this product.
Trace mineral that pairs with zinc in connective-tissue enzymes.
Strongest study designs first
RCT Cesarean RCT of copper-impregnated dressings (topical)—not oral copper gluconate 1 mg; delivery-route mismatch.
Clinical study Prospective copper-dressing study on hard-to-heal wounds; topical copper oxide dressings—not oral gluconate and not this supplement.
Bovine collagen peptides — types abundant in skin and soft tissue.
Strongest study designs first · top 3 shown
Systematic review Systematic review: oral nutritional supplements had variable effects on wound healing across wound types.
Systematic review Systematic review: preliminary evidence for oral collagen in wound healing and skin aging; generally safe.
RCT Pragmatic multicenter RCT (hospitalised pressure-ulcer patients): no significant benefit of intensive nutrition or wound-healing supplements (null result).
RCT Burn RCT: oral hydrolyzed collagen-based supplement improved wound-healing rate vs placebo; burn setting and higher protein intake—not this 400 mg dose alone.
RCT Collagen peptide supplementation research
RCT Multicenter RCT (n=89, pressure ulcers, 8 weeks): a fortified collagen protein hydrolysate supplement three times daily roughly doubled the PUSH healing rate vs placebo.
Animal study Animal (rat) study: dietary collagen hydrolysate increased skin type I/IV collagen and reduced MMP-2 activity
Pineapple enzyme studied in postoperative comfort and wound-care contexts.
Strongest study designs first · top 3 shown
Meta-analysis Systematic review/meta-analysis: moderate-quality studies support oral bromelain for pain control and topical bromelain in wound care; no major health risks reported.
Meta-analysis Systematic review/meta-analysis (third-molar surgery): oral bromelain gave moderate relief of postoperative discomfort.
RCT Tibrolin (trypsin + bromelain + rutoside) RCT in surgical wound management — combination enzyme tablet study, not this bottle
RCT RCT (third-molar surgery): bromelain alone moderately reduced swelling, not significantly vs no drug; best results combined with dexamethasone.
RCT RCT (third-molar surgery): less inflammatory response with bromelain than control.
Curcuma longa — curcuminoids studied in inflammation and nutrition research.
Strongest study designs first
RCT Open-label RCT (laparoscopic hysterectomy): no pain difference at 24 h; lower pain at 72 h with curcuminoids.
RCT Pilot RCT (laparoscopic gynecologic surgery): curcuminoids reduced postoperative pain severity.
Review Nutrition and wound-healing overview discussing curcumin
Raises plasma arginine more efficiently than oral arginine in published PK work.
Mechanism studied: Oral L-citrulline raised plasma L-arginine more effectively than L-arginine itself in a crossover PK study. Schwedhelm 2008
Strongest study designs first · top 3 shown
Meta-analysis Systematic review/meta-analysis on arginine and glutamine: authors conclude wound healing might be enhanced by supplementation at the right dose.
Systematic review Systematic review (pressure ulcers): arginine shows potential but evidence remains inconclusive; glutamine was only studied with arginine.
RCT Arginine-pathway research. Multicenter RCT (n=200 malnourished adults with pressure ulcers, 8 weeks): a formula enriched with arginine, zinc and antioxidants reduced ulcer area more (60.9% vs 45.2%).
RCT Schwedhelm et al., Br J Clin Pharmacol 2008 — oral citrulline vs arginine / NO metabolism
Review Review: L-citrulline/watermelon supplementation and vascular function via the L-arginine/nitric oxide pathway.
Review Review of the pharmacokinetics of arginine, ornithine and citrulline.
Amino acid studied in surgical and burn nutrition research.
Strongest study designs first · top 3 shown
Meta-analysis Systematic review/meta-analysis (severe burns): enteral glutamine may not improve mortality; may be associated with shorter stay and fewer wound infections.
Meta-analysis Systematic review/meta-analysis (burns): apparent benefits came from small single-centre trials; authors do not recommend routine use.
Meta-analysis Systematic review/meta-analysis on arginine and glutamine: wound healing might be enhanced by supplementation at the right dose.
Meta-analysis Meta-analysis of IV glutamine dipeptide in major abdominal surgery: shorter hospital stay but no clear cut in morbidity—IV dipeptide, not 175 mg oral L-glutamine.
Meta-analysis Systematic review/meta-analysis (critically ill): enteral glutamine gave no significant clinical benefit except reduced hospital stay; possible burn benefit on sparse data.
RCT RE-ENERGIZE RCT (n=1,200, severe burns): enteral glutamine did not reduce time to discharge alive
Sodium hyaluronate — extracellular matrix glycosaminoglycan.
Strongest study designs first
RCT Oral HA RCT improved skin hydration/tone (100–200 mg/day)—skin condition study, not surgical-wound healing; dose above this product’s 15 mg.
RCT Topical HA gel after palatal graft surgery improved pain and epithelialization; topical oral-surgery use—not oral sodium hyaluronate capsules.
Probiotic strain included for gut support during recovery.
Strongest study designs first
RCT LA14 in a multi-ingredient GERD supplement RCT—LA14 present but combo product and GI symptom endpoint, not peri-operative wound support.
RCT La-14 (+HN001) oral RCT in 50 healthy women: vaginal microbiota remained stable and colonisation was not detected; not a surgery or wound trial—La-14 matched, indication mismatch.
Companion probiotic in the same serving.
Strongest study designs first · top 3 shown
Meta-analysis Multi-strain probiotic research. Meta-analysis of placebo-controlled RCTs (colorectal cancer surgery): probiotics/synbiotics associated with lower infection (OR 0.34) and septicemia incidence.
Meta-analysis Systematic review/meta-analysis (colorectal cancer surgery): probiotics reduced overall infection (OR 0.51) and incision infection (OR 0.59).
Meta-analysis Network meta-analysis (surgical patients): synbiotics ranked first for reducing surgical-site infection, pneumonia, sepsis, stay and antibiotic use.
RCT Trauma ICU RCT: 4-strain probiotic including L. plantarum UBLP-40 reduced SSI vs placebo; multi-strain (not this bottle alone) and strain mismatch vs unspecified L. plantarum 5 mg.
RCT Colorectal surgery RCT: 4-probiotic mix including L. plantarum cut SSI/pneumonia/leak rates; combo regimen—not single-strain plantarum at this dose.
RCT Elective surgery RCT of L. plantarum 299v: no effect on translocation or septic morbidity—null result; strain 299v ≠ this product’s unspecified plantarum.
Piper nigrum — included to support turmeric absorption.
Strongest study designs first
Clinical study 2025 crossover PK reappraisal: piperine added no benefit for unconjugated curcumin exposure—mixed literature vs older Shoba findings.
Clinical study Classic human PK: 20 mg piperine with 2 g curcumin raised measured curcumin bioavailability; relevant to turmeric co-ingestion—dose far above 2 mg extract, not wound healing.
Wound dressing gel · 32 ppm molecular / nano-silver · external use only
A clear, water-based gel built around 32 ppm molecular silver. Free Life Labs materials describe gradual silver-ion release and a protective moist wound environment without alcohol, sting, or sulfa.
Regulatory status: Wound dressing gel made in an FDA-registered facility
Labeling describes “management of” these wound types — not a treat-or-cure claim. External use only. See a clinician for serious or non-healing wounds.
Meta-analysis of 7 RCTs (650 patients): better healing rate, faster complete healing, shorter hospital stay and better infection resolution. No significant difference in ulcer-area reduction.
Meta-analysis of 5 RCTs (n=285): infections were 9.5% vs 27.8% with older silver formulations, with lower pain and cost where reported.
There is insufficient evidence to establish whether silver dressings or topical agents promote wound healing or prevent wound infection.
Published research describes how Ag+ (silver ions) — not solid silver metal — act as a broad-spectrum antiseptic in lab and dressing studies: attaching to and damaging bacterial membranes, binding thiol groups on proteins, and condensing DNA. These papers study Ag+ and silver hydrogels as ingredients or dressings — in-vitro and dressing research, not a claim that this tube treats, cures, or prevents infection.
Mechanism studied: In vitro, Ag⁺ detached bacterial membranes from the cell wall, condensed DNA and inactivated proteins. Feng 2000
Strongest study designs first · top 3 shown
Meta-analysis Meta-analysis of 7 RCTs (650 patients, diabetic foot ulcers): silver dressings improved healing rate, time to healing, hospital stay and infection resolution; no significant effect on ulcer-area reduction.
Meta-analysis Meta-analysis of 5 RCTs in burns (n=285): nanocrystalline silver vs older silver formulations—infection 9.5% vs 27.8%, lower pain; mixed results for length of stay.
Meta-analysis Meta-analysis of RCTs (lower-extremity ulcers): silver dressings significantly benefited diabetic-foot-ulcer healing; the venous-ulcer effect was positive but not significant.
Meta-analysis Meta-analysis (burns): silver-containing hydrofiber shortened healing time and reduced inflammatory reactions vs silver sulfadiazine; safety needs further analysis.
Meta-analysis Systematic review/meta-analysis (burns): nanocrystalline silver vs silver sulfadiazine/silver nitrate associated with shorter stay, less pain, fewer procedures and lower infection rates.
Meta-analysis Cochrane review (diabetic foot ulcers): antimicrobial dressings vs non-antimicrobial may increase the number of ulcers healed; trials few, small and often poorly designed.
Meta-analysis Meta-analysis of RCTs (clean/clean-contaminated surgery): silver dressings were not associated with fewer surgical-site infections than silver-free dressings; very low-quality evidence.
Meta-analysis Cochrane review: uncertain whether any wound dressing, including silver, reduces surgical-site infection in wounds healing by primary intention.
Systematic review Cochrane review: insufficient evidence to establish whether silver dressings or topical agents promote healing or prevent wound infection.
RCT Double-blind randomized study (n=80, non-ischemic DFU): silver-nanoparticle gel dressing had a higher weekly healing rate than conventional dressing.
RCT RCT (outpatient adult burns): no efficacy or safety difference between nanocrystalline silver and 1% silver sulfadiazine; higher dressing cost.
RCT Adhya et al., 2014 — nano-crystalline silver hydrogel vs silver sulfadiazine in second-degree burns (wound-dressing study).
Review Rai et al., 2009 — silver nanoparticles as a new generation of antimicrobials (review).
Review Chopra, 2007 — increasing use of silver-based products as antimicrobial agents (review).
Review Lansdown, 2002 — “Silver I: its antibacterial properties and mechanism of action.”
In vitro Jung et al., 2008 — electrically generated Ag+; >5-log reduction of S. aureus and E. coli at 90 min with membrane damage.
In vitro Feng et al., 2000 — mechanistic Ag+ study on E. coli and S. aureus (membrane detach, DNA condensation, protein inactivation).
Not for deep puncture wounds, animal bites, or serious burns. Do not use in eyes or on mucous membranes. Stop if irritation occurs.
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Request clinic samples or talk through a formula with our team.
Summaries of published ingredient research for clinician reference; not product trials unless stated. For NerveReverse Formula and WoundWorx Surgery Supplement: these statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.
