DavidPerlmutterMD · 2024-04-22 · David Perlmutter (host), Paul Fernyhough, Nigel A. Calcutt

Exciting Developments in the Treatment of Peripheral Neuropathy | Dr. Fernyhough & Dr. Calcutt

40 research-tied claims examined: 3 overstated 1 context 31 supported 5 unverified

Overstated

0:13:30 David Perlmutter (host)overstatedmoderate

Co-administration of intravenous glutathione with platinum-based chemotherapies significantly reduces the incidence of peripheral neuropathy.

"the co-administration of intravenous glutathione, as it relates to at least the platinum-based chemotherapy agents, was pretty dramatic in terms of reducing the number of those individuals who ended up with a peripheral neuropathy problem." (said at 0:13:30)

Although early randomized controlled trials showed marked reductions in moderate-to-severe neurotoxicity (for example, a 2002 double-blind trial of 52 patients receiving oxaliplatin found grade 2–4 neuropathy in 2 of 21 patients receiving IV glutathione versus 11 of 19 receiving placebo after 8 cycles), broader evidence across platinum-treated cohorts is mixed and inconclusive. Subsequent randomized trials have found no significant reduction in overall neurotoxicity incidence between glutathione and control groups (e.g., 90.0% vs 92.9% after 9 cycles), and systematic Cochrane reviews have concluded that available trials provide insufficient high-quality evidence to establish reliable prevention of platinum-induced peripheral neuropathy.

supports: Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advance… (Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2002) · cited 419x in the literature
"With regard to grade 2 to 4 National Cancer Institute common toxicity criteria, 11 patients experienced neuropathy in the placebo arm compared with only two patients in the GSH arm (P =.003). After 12 cycles, grade 2 to 4 neurotoxicity was observed in three patients in the GSH arm and in eight patients in the placebo arm (P =.004)." (abstract, results, passage verified)
pubmed full study (doi)
contradicts: [Assessment of the protective effect of calcium-magnesium infusion and glutathione on oxal… (Zhonghua zhong liu za zhi [Chinese journal of oncology] 2010) · cited 13x in the literature
"After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms." (abstract, results, passage verified)
pubmed
partial: Interventions for preventing neuropathy caused by cisplatin and related compounds. (The Cochrane database of systematic reviews 2014) · cited 301x in the literature
"Of the seven eligible glutathione trials (387 participants), one used quantitative sensory testing but reported only qualitative analyses." (abstract, results, passage verified)
pubmed full study (doi)

0:26:45 Nigel A. Calcuttoverstatedmoderate

Ruth van Heyningen discovered in the 1950s that aldose reductase is expressed at high levels in organs where diabetic complications occur, including the eyes, nerves, blood vessels, and kidneys.

"The the the the primary observation was made by a lady named Ruth van Heyningen in the 1950s, who looked at the distribution of aldose reductase and noted that it it just happened to be present in all the organs of the body where you got diabetic complications. The eyes, the nerves, the blood vessels, the kidneys, these were all at levels with high expression of aldose reductase." (said at 0:26:45)

Biochemist Ruth van Heyningen discovered the presence of aldose reductase and the sorbitol (polyol) pathway in the ocular lens in 1959, linking polyol accumulation to the formation of sugar and diabetic cataracts. However, she did not map its distribution across the full spectrum of organs affected by diabetic complications in the 1950s. The identification of aldose reductase activity in other non-insulin-dependent tissues susceptible to diabetic complications—such as peripheral nerves, blood vessels, and the kidneys—and the broader formulation of the polyol hypothesis for systemic diabetic microvascular complications occurred in subsequent decades through work by researchers such as Kenneth Gabbay and Jin Kinoshita.

context: All in the family: aldose reductase and closely related aldo-keto reductases. (Cellular and molecular life sciences : CMLS 2004) · cited 202x in the literature
"Aldose reductase catalyzes the first step in the polyol pathway and is thought to be involved in the pathogenesis of diabetic complications." (abstract, passage verified)
pubmed full study (doi)
context: Aldose reductase, ocular diabetic complications and the development of topical Kinostat(®)… (Progress in retinal and eye research 2016) · cited 90x in the literature
"Among these, the two-step sorbitol pathway has been the most extensively investigated; nevertheless, it remains controversial. To date, long-term pharmacological studies in animal models of diabetes have demonstrated that the onset and development of ocular complications that include keratopathy, retinopathy and cataract can be ameliorated by the control of excess metabolic flux through aldose reductase (AR)." (abstract, passage verified)
pubmed full study (doi)

0:56:02 Nigel A. Calcuttoverstatedmoderate

WinSanTor has completed two Phase 2 clinical trials showing that topical pirenzepine stimulates nerve regrowth and improves patient-reported outcomes in neuropathy.

"And WinSanTor, with help from Canadian government and the US government, has concluded two phase two clinical trials. Now, both of which have shown success in in showing nerve regrowth and other patient descriptors of effect." (said at 0:56:02)

The speaker claims that two Phase 2 clinical trials have concluded, both demonstrating nerve regrowth and patient-reported improvements. To date, published clinical trial data exist for only one Phase 2a randomized, double-blind, placebo-controlled trial evaluating topical 4% pirenzepine in 58 participants with diabetic peripheral neuropathy (PMID 41352124). While this trial demonstrated a statistically significant increase in lower-limb intraepidermal nerve fibre density (IENFD) over 24 weeks compared to placebo, the patient-reported outcome (Norfolk QOL-DN score) showed no significant difference in the primary modified intent-to-treat (mITT) analysis set. Improvement in QOL was observed only in a per-protocol secondary analysis, which the study authors noted requires cautious interpretation due to potential bias. Claiming that two Phase 2 trials have completed and successfully demonstrated both nerve regrowth and patient-reported benefits overstates the published evidence.

partial: Topical application of the antimuscarinic pirenzepine increased lower limb nerve fibre den… (EBioMedicine 2026) · cited 3x in the literature
"Topical pirenzepine administered once daily for 24 weeks in patients with DPN resulted in a statistically significant growth of nerve fibres as measured by IENFD at the ankle. ... There was a 10.4-point improvement in the Norfolk QOL-DN score in the combined treatment groups over placebo (p < 0.001) in the per protocol (PP) analysis set, but no difference was observed in the modified intention-to-treat analysis, suggesting the need for cautious interpretation of the PP result due to potential bias." (abstract, results and conclusions)
pubmed full study (doi)

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.