Chemotherapy-induced peripheral neuropathy and Vitamin D, Omega-3

Chemotherapy-induced peripheral neuropathy might be 3X more likely if low Vitamin D - Nov 2026

Vitamin D status and chemotherapy-induced peripheral neuropathy in patients with cancer: a systematic review with exploratory quantitative synthesis.

Support Care Cancer 34, 1203 (2026). https://doi.org/10.1007/s00520-026-11456-6 PDF behind paywall

Wei, J., Chang, C., Li, M. et al.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a clinically important toxicity of neurotoxic anticancer therapy. This review evaluated whether serum or plasma 25-hydroxyvitamin D (25(OH)D) status is associated with CIPN risk or severity in patients with cancer.

Methods: The protocol was prospectively registered in PROSPERO (CRD420261438011). PubMed, Web of Science, and the Cochrane Library were searched from database inception through 23 June 2026. Eligible English-language human studies reported vitamin D status and CIPN-related outcomes during or after neurotoxic anticancer therapy. Vitamin D measurement timing was coded, risk of bias was assessed using ROBINS-E, and adjusted and unadjusted estimates were synthesized separately. Two-study pooled models were prespecified as exploratory.

Results: Fourteen records contributed evidence. Exploratory adjusted pooling for severe CIPN included two studies and showed a common-effect odds ratio (OR) of 1.81 (95% confidence interval (CI) 1.32-2.49; I2 92.4%);

the random-effects OR was 2.94 (95% CI 0.63-13.73). Exploratory adjusted pooling for any CIPN included two studies and showed a common-effect OR of 2.76 (95% CI 1.70-4.48; I2 70.5%) and a random-effects OR of 3.36 (95% CI 1.20-9.43).

Most evidence had high or very high risk of bias, and the pooled models should be interpreted as hypothesis-generating rather than confirmatory.

Conclusion: Low vitamin D status may be associated with greater CIPN risk or severity, particularly when measured before treatment or at baseline. The evidence remains hypothesis-generating because of small study numbers, heterogeneity, and risk of bias.

38 references online

Chemotherapy-induced peripheral neuropathy: Vitamin D, Omega-3

Claude AI Nov 2026

CIPN is nerve damage caused by certain cancer drugs. The longest sensory nerves are hit first, so symptoms start in the toes and fingertips and spread upward in a "stocking-and-glove" pattern. It is one of the most common reasons oncologists cut or stop chemotherapy, and for a sizable minority it becomes permanent.

Drugs that cause it

Class	Examples	Notable features
Taxanes	paclitaxel, docetaxel, nab-paclitaxel	Mainly sensory; worsens with cumulative dose
Platinum	oxaliplatin, cisplatin (carboplatin less so)	Acute cold-triggered symptoms with oxaliplatin; can worsen after the last dose ("coasting")
Vinca alkaloids	vincristine, vinblastine	Sensory, motor and autonomic (e.g., constipation)
Proteasome inhibitors	bortezomib	Painful small-fiber type
Immunomodulators	thalidomide	Often irreversible
Antibody-drug conjugates	brentuximab vedotin, enfortumab vedotin	Payload disrupts microtubules

Symptoms and how common it is

Numbness, tingling, burning or electric-shock pain, and loss of vibration sense.
Poor balance and falls, plus trouble with fine tasks like buttons and typing.
Cold sensitivity: oxaliplatin causes an acute cold-triggered syndrome in 85–95% of patients [OxaNeuro protocol].
A meta-analysis of 31 studies (4,179 patients) found CIPN in 68% of patients in the first month after chemo, 60% at 3 months and 30% at 6 months or later [Seretny 2014].

Mechanisms (briefly)

Taxanes and vincas disrupt the microtubules that carry material along axons.
Platinum drugs form DNA adducts in dorsal root ganglion neurons, which sit outside the blood–nerve barrier.
Shared downstream damage: mitochondrial dysfunction, oxidative stress, ion-channel changes, neuroinflammation and loss of small nerve fibers in the skin.

Risk factors

Higher cumulative dose
Neuropathy before treatment starts
Diabetes
Older age
Smoking
Reduced kidney function [Seretny 2014]
Self-reported Black race
Low vitamin D (see below)

What the guidelines say

ASCO's 2020 guideline is still listed as current (last updated April 2023) [ASCO status]. Its main points [ASCO 2020]:

No drug is recommended for prevention. Acetyl-L-carnitine is actively discouraged, because it made CIPN worse in a SWOG trial.
During treatment, the main tool is to delay, reduce, swap or stop the neurotoxic drug.
For established painful CIPN, duloxetine is the only drug with adequate evidence, and its benefit is modest.

Non-drug prevention with growing evidence

Compression: In a 63-patient taxane trial, 64.7% of the compression group met the success criterion at 12 weeks, versus 41.1% for both cryotherapy and placebo. Only 35% of the cryotherapy group stuck with it, versus 73% for compression [[CONTRoL results](https://naturalmedicinejournal.com/journal/compression-therapy-versus-cryotherapy-for-chemo-neuropathy)] [CONTRoL abstract]. A phase III trial (SWOG S2205) is now comparing cryocompression, continuous compression and low cyclic compression [S2205].
Exercise: The STOP trial randomized 158 patients on oxaliplatin or vinca alkaloids. Supervised sensorimotor/balance training (twice a week, 15–30 minutes) cut CIPN incidence to 30%, versus 70.6% with usual care. Whole-body vibration training gave 41.2% [STOP 2024]. In a 355-patient trial, home walking plus resistance exercise also reduced symptoms [Kleckner 2018].

Vitamin D

Vitamin D, the SWOG S0221 analysis (1,191 women on paclitaxel):

One-third had pretreatment 25(OH)D ≤20 ng/mL.
Severe (grade ≥3) CIPN occurred in 20.7% of the insufficient group versus 14.2% of the sufficient group (OR 1.57).
In mice, a vitamin D-deficient diet caused nerve hypersensitivity and made them more sensitive to paclitaxel [Chen 2023].
77% of Black patients were insufficient, versus 28% of White patients, and Black patients also had about twice the CIPN rate [Drug Topics].

Vitamin D, an earlier 37-patient cohort: Vitamin D was the only one of four nutrients measured (with B12, folate and homocysteine) that was deficient often enough to analyze. Lower baseline levels predicted worse neuropathy [Jennaro 2020].

Caveats: These are association studies. S0221 didn't record grade 2 CIPN, diabetes or pre-existing neuropathy. I found no completed RCT showing that vitamin D supplementation prevents CIPN. Two trials are underway:

VCU: patients below 20 ng/mL are randomized to vitamin D replacement adjusted to blood levels, versus advice to take over-the-counter vitamin D. Completion is projected for 2030 [VCU trial].
Egypt: 132 patients below 30 ng/mL receive D3 with paclitaxel [NCT06596122].

Omega-3

A small double-blind RCT gave 640 mg three times daily during paclitaxel and for a month after. About 30% of the omega-3 group developed neuropathy versus about 59% on placebo (OR 0.3). Severity and nerve-conduction results did not differ significantly [Ghoreishi 2012].
The larger Danish OxaNeuro trial is testing 3 g/day EPA+DHA against corn oil for 8 months in 120 oxaliplatin patients [OxaNeuro]. I found no published results yet.

Bottom line: CIPN is common, often long-lasting and hard to treat. The best-supported options right now are adjusting the chemo dose, compression and supervised balance training. Testing and correcting vitamin D before chemo is cheap and low-risk, and the link with CIPN has been confirmed in a large trial dataset. The SWOG investigators suggest it, but no outcome trial has shown it works yet.