Supplements for Chemo Neuropathy: Hits, Misses & Hidden Risks
What is the evidence for B complex, Magnesium and Omega-3?
In the first part of this series about chemo-induced peripheral neuropathy (CIPN), we mostly talked about prevention. If you haven’t read the article, you can read it here: Saving Your Hands And Feet From Chemo
Due to the immensity of this topic (the more I looked, the more I had to say), this week, we’ll take a deep dive into supplements often prescribed for CIPN and we’ll look at integrative approaches next week. Plus, Double-zero sent me this fascinating article about herbs for CIPN that I want to look into.
Neuropathic Pain Medications
I won’t write too much about pharmaceuticals. There is plenty of info out there about drugs and I don’t have too much to add to the stack.
Suffice to say, for painful neuropathy specifically, duloxetine remains the agent with the most (albeit modest) evidence. Other agents like gabapentin, pregabalin, and amitriptyline are sometimes used empirically, but phase 3 RCTs for gabapentin and amitriptyline in CIPN have not shown benefit over placebo1.
Admittedly, I have written many prescriptions for pregabalin over the years and despite the RCTs reporting no benefit, many of my patients did see some pain relief from CIPN.
B-Complex Supplements
This one was disappointing, because I was recommending B-complex supplementation to patients with neuropathy as a supplement that could improve nerve health and likely wouldn’t cause harm.
The evidence says otherwise.
The only randomised, placebo-controlled trial found B vitamin supplementation was not superior to placebo for preventing CIPN during chemotherapy with oxaliplatin, taxanes, or vincristine2. However, the authors noted that patients reported improved sensory symptoms.
Interestingly, one small study found that higher plasma vitamin B6 levels during chemotherapy were associated with lower chronic CIPN severity in colorectal cancer patients3. This doesn’t necessarily mean supplementation will replicate the effect. It may simply reflect better nutritional status as a marker of overall health. I’ll tell you why.
Caution With Pyridoxine (Vitamin B6)
I am cautious about recommending Vitamin B6 supplementation for CIPN as pyridoxine is itself neurotoxic at higher doses. Past a certain threshold, it can cause sensory ataxic neuropathy (loss of balance and coordination). Some of my patients have complained of tingling up the spine, electric shock sensations down the arms and even progressive neuropathy! Fortunately, these side effects went away with ceasing supplementation.
As of March 2023, the Therapeutic Goods Administration (TGA) in Australia requires products containing B6 at daily doses above 10 mg to carry a label warning for neuropathy risk.
The half-life of pyridoxine HCl is up to 30 days, meaning repetitive small doses can accumulate over months. Neuropathy can occur with daily doses less than 50 mg but some supplements contain up to 100 mg of B6.
Vitamin B6 is also a common inclusion in magnesium supplements, multivitamins, B-complex supplements, and various ‘wellness’ formulations. Cumulative intake from multiple products may far exceed the safe threshold. If your supplement contains activated or methylated B6, you may be at even higher risk of side effects.
Before you forget, stop reading and check your supplement cabinet for hidden B6.
Based on these findings, I’ve concluded that checking and correcting a documented folate or B12 deficiency is reasonable since deficiency independently causes neuropathy. However, routine B-complex supplementation is not supported by current evidence and carries the specific risk of pyridoxine neurotoxicity.
Magnesium
I love magnesium, prescribe it regularly to patients and personally take it myself so I was happy to see there were no red flags in the literature.
In fact, current evidence for magnesium and CIPN is promising although still limited and mostly observational.
A prospective study of 196 colorectal cancer patients showed that higher dietary magnesium intake during chemotherapy was associated with lower prevalence of chronic CIPN4.
Another study in colorectal patients receiving oxaliplatin found that low pretreatment serum magnesium was associated with increased risk and severity of acute oxaliplatin‑induced peripheral neuropathy5. Again, we see the importance of testing.
However, if you were told your magnesium level was fine, this is usually a blood (serum) measurement. When circulating levels of magnesium are low, other tissues provide magnesium to restore circulating magnesium levels. With low magnesium intake, body stores of magnesium could be depleted, while circulating levels are still in the healthy range.
In this case, you could still benefit from additional intake of magnesium. Dietary intake or supplementing with magnesium could restore depleted body stores of magnesium, increasing availability of magnesium in muscles and nerves. This could be neuroprotective and improve CIPN symptoms.
What About IV Magnesium?
Early retrospective work suggested that IV calcium–magnesium infusions around oxaliplatin reduced neurotoxicity6 but later larger randomized trials failed to confirm benefit7.
Therefore, intravenous Ca/Mg for oxaliplatin‑induced CIPN is not routinely recommended in current guidelines, but the underlying magnesium-nerve function link remains mechanistically relevant.
Side note: Anecdotally, most of my patients who had acute (not CIPN) neurotoxicity from oxaliplatin during or just after infusion benefited from the addition of IV Magnesium infusion prior to chemo. However, I never infuse IV calcium unless patients are proven hypocalcaemic. We’ll talk about why I don’t like calcium supplements in another article.
Omega-3 Supplements
Evidence on omega-3 for CIPN is mixed, with some positive preclinical and clinical trials but negative results from others. A 2012 randomized double-blind placebo trial in breast cancer patients receiving paclitaxel found omega-3 (640 mg t.i.d) reduced CIPN incidence to 30% vs. 59% in the placebo arm8. A systematic review published in 2019 reported (with low certainty) lower neuropathy incidence (RR=0.58) and better sensory nerve preservation with omega-39.
Then you have a 2023 randomized controlled trial in breast cancer patients on weekly paclitaxel using 4g omega-3 showing no reduction in acute pain syndrome (84% vs. 88%) or CIPN scores with trends toward worse symptoms10.
An umbrella meta-analysis, along with many other studies, has shown that omega-3 fatty acids can reduce systemic inflammation markers such as CRP, TNF-α, and IL-611. While there is currently no direct clinical evidence supporting omega-3 supplementation for patients with elevated inflammatory markers to prevent or treat CIPN, it seems biologically plausible that it could help.
In cases of high CRP, ferritin, or other inflammation-related markers, I would consider omega-3 supplementation if there is no contraindication.
That’s all for this week folks. I hope this article was enlightening. For those awaiting the big hitters like IV glutathione and ALA, that will come next week. I promise!
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This information is for education only and not a substitute for medical advice. Always consult your healthcare team before making changes to treatments, supplements, or lifestyle. While every effort is made to ensure information is accurate and evidence-informed, no guarantee can be given. The author accepts no responsibility for any loss or harm that may arise from reliance on the information provided.
Nicely done! We counsel our patient’s similarly.
I’m not sure if it’s the placebo effect but the Pregabalin does help me with the neuropathy.