Supplements

WHAT THEY ARE MEANT TO DO

Chemotherapy and pelvic radiotherapy damage the intestinal epithelium and change the composition of the gut flora, and diarrhoea is a common reason for dose reduction or treatment interruption. Probiotics, that is live bacteria (most often Lactobacillus and Bifidobacterium), are intended to restore that flora and strengthen the gut barrier ^[2].

WHAT THE POOLED ANALYSES SHOW

• a systematic review of 29 randomised trials: lower incidence of diarrhoea with probiotics (RR 0.67; 95% CI 0.47–0.95) and a stronger effect with synbiotics (RR 0.51; 95% CI 0.29–0.89) ^[1];
• a meta-analysis of 18 trials and 1,526 patients with colorectal cancer: RR 0.51 (95% CI 0.40–0.64) and shorter duration of diarrhoea ^[3];
• a meta-analysis of 14 trials during fluoropyrimidine- or irinotecan-based chemotherapy: RR 0.40 (95% CI 0.27–0.60), NNT 3–5, meaning in theory one case of diarrhoea avoided per 3–5 people treated ^[4];
• a meta-analysis of 8 trials and 753 patients with leukaemia: OR 0.39 (95% CI 0.26–0.57) ^[8].

WHY WE STILL DO NOT WRITE THAT PROBIOTICS WORK: The largest and best-designed trial in this field — a multicentre, double-blind, placebo-controlled phase 3 study in 233 patients with colorectal cancer receiving irinotecan — failed its primary endpoint ^[5]. Grade 3–4 diarrhoea occurred in 7.9% of those taking a mixture of Bifidobacterium BB-12 and Lactobacillus rhamnosus GG versus 11.8% on placebo (p=0.38); diarrhoea of any grade in 41.2% versus 46.2% (p=0.51). The authors stated plainly that the results indicate a LACK of benefit. This is the classic pattern in which an effect shrinks as trial quality rises: many small trials show benefit, one large trial does not confirm it. In that situation the more cautious reading is the correct one.

WHAT THE GUIDELINES SAY

The MASCC/ISOO panel "suggests" that probiotics containing Lactobacillus species be used to prevent diarrhoea in patients receiving chemotherapy and/or radiotherapy for a pelvic malignancy, at level of evidence III ^[6]. This is the weakest category of recommendation and a narrow population — it is not a recommendation for every person with cancer.

WHEN PROBIOTICS SHOULD NOT BE TAKEN WITHOUT TALKING TO A DOCTOR:

• profound neutropenia, haematopoietic stem-cell transplantation, immunosuppressive treatment;
• mucositis of the gastrointestinal tract, a damaged gut barrier, a central venous catheter;
• ongoing immune-checkpoint immunotherapy (a separate question — see the entry "Probiotics and immunotherapy").

SAFETY: In the phase 3 trial no infection caused by the strains used was observed ^[5]. The risk is nonetheless not zero: a case has been described of a patient with advanced lung cancer in whom a bacterium from a probiotic fermented-milk drink caused a bloodstream infection, and the strain cultured from blood was genetically identical to the strain in the product ^[7]. The precondition was a combination of two factors: reduced immunity and a breach in the gastrointestinal wall.

WHAT THESE RESULTS DO NOT SAY

The absence of a proven benefit from probiotics does not mean that treatment-related diarrhoea does not need treating — on the contrary, it is a complication that can force chemotherapy to be interrupted and requires management agreed with the treating team. Nor do these results say anything about probiotics as a way of treating the cancer itself; none of the studies discussed tested that.

Sources

1. [1] Rachmawati et al. — The Role of Probiotics, Prebiotics, and Synbiotics for Reducing Chemotherapy-Induced Gastrointestinal Toxicity, Rom J Intern Med 2026 (29 RCT): europepmc.org ↗
2. [2] Salehi et al. — Gut microbiome dysbiosis and cancer: a systematic review on the emerging role of probiotics in oncology, Crit Rev Oncol Hematol 2026: europepmc.org ↗
3. [3] Yang et al. — Efficacy and safety of probiotics in preventing chemotherapy-related diarrhea in colorectal cancer, Medicine 2025 (18 RCT, n=1526): europepmc.org ↗
4. [4] Siritientong et al. — Oral probiotic supplementation to alleviate diarrhea induced by fluoropyrimidines or irinotecan-based chemotherapy, Complement Ther Med 2025 (14 RCT w metaanalizie): europepmc.org ↗
5. [5] Mego et al. — Randomized double-blind placebo-controlled multicenter phase III study of prevention of irinotecan-induced diarrhea by a probiotic mixture (BB-12 + LGG), Front Oncol 2023 (n=233): pmc.ncbi.nlm.nih.gov ↗
6. [6] Lalla et al. — MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy, Cancer 2014 (sugestia, poziom dowodów III): acsjournals.onlinelibrary.wiley.com ↗
7. [7] Lacticaseibacillus paracasei bacteremia secondary to esophageal invasion by pleomorphic carcinoma — case report, BMC Infect Dis 2026: europepmc.org ↗
8. [8] Chen et al. — Can probiotics reduce chemotherapy-induced complications in leukemia patients?, Nutr Clin Pract 2026 (8 RCT, n=753): europepmc.org ↗

WHY PEOPLE TAKE IT

Glutamine is an amino acid absorbed from food, also synthesised by the body and stored mainly in muscle and lungs ^[1]. In oncology it is bought chiefly for mucositis, chemotherapy-induced peripheral neuropathy, gastrointestinal side effects and muscle weakness ^[1].

WHAT THE EVIDENCE SHOWS

Memorial Sloan Kettering states that studies SUGGEST glutamine or its derivatives are useful against mucositis, and that it may help prevent numbness and tingling caused by oxaliplatin and vincristine; intravenous glutamine also reduced chemotherapy-induced nausea, vomiting and diarrhoea in patients with gastric or colorectal cancer ^[1]. Findings from cachexia trials are MIXED ^[1].

WHAT THE GUIDELINES SAY — AND WHY THAT OUTWEIGHS SINGLE TRIALS. The 2014 MASCC/ISOO guidelines carried a recommendation AGAINST intravenous glutamine for the prevention of oral mucositis in patients receiving high-dose chemotherapy for haematopoietic stem cell transplantation ^[2]. The 2019 update identified new evidence but judged it inadequate and conflicting, and for that reason issued NO guideline for glutamine at all ^[3]. That is the honest state of knowledge: not “it works”, not “it does not work”, but “the evidence is too weak to recommend anything”.

A SEPARATE CONCERN, INDEPENDENT OF EFFICACY. Glutamine transporters are upregulated in tumour cells and glutamine may promote their growth and survival, so supplementation during cancer requires careful consideration ^[1].

INTERACTIONS WITH CANCER AND OTHER TREATMENT

• lactulose — glutamine may reduce its ammonia-lowering effect ^[1];
• methotrexate — glutamine may increase tumour retention of methotrexate, potentially enhancing its effect ^[1].

SAFETY. Reported effects include peripheral oedema, gastrointestinal symptoms, headache, fever and infections ^[1]. One case report documented severe abdominal pain with liver damage requiring discontinuation ^[1].

WHAT THIS MEANS

Glutamine is often presented as a harmless “building block” because the body makes it naturally. The evidence does not support that framing, and in one specific setting (intravenous form, stem cell transplantation) scientific societies explicitly advised against it. Any decision about supplementation during cancer treatment belongs to the treating physician, who knows the full medication list. This entry is not medical advice.

Sources

1. Memorial Sloan Kettering Cancer Center — About Herbs: Glutamine: mskcc.org ↗
2. Lalla RV i wsp. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014: acsjournals.onlinelibrary.wiley.com ↗
3. Elad S i wsp. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy (aktualizacja 2019). Cancer 2020: acsjournals.onlinelibrary.wiley.com ↗

WHY THIS ENTRY DIFFERS FROM THE REST OF THE CATALOGUE: Most entries here describe preparations a patient considers on their own, where the evidence is weak or conflicting. This one is the opposite. Folic acid and vitamin B12 with pemetrexed are part of the treatment regimen: not 'support', but a condition of delivering that treatment safely. Pemetrexed acts by targeting the folate pathway ^[2], so the body's folate and vitamin B12 status translates directly into the severity of adverse effects.

THE EVIDENCE THAT CHANGED A PROTOCOL MID-TRIAL

In the phase 3 trial comparing pemetrexed plus cisplatin with cisplatin alone in malignant pleural mesothelioma, folic acid and vitamin B12 were added to the protocol during recruitment - after 117 patients had enrolled - specifically in order to reduce toxicity ^[1]. The authors report that this resulted in a significant reduction in toxicities in the pemetrexed/cisplatin arm ^[1], and that the addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time ^[1]. Median survival in that trial was 12.1 months with pemetrexed plus cisplatin versus 9.3 months with cisplatin alone (p = .020) ^[1].

THIS IS AN UNUSUAL EVIDENTIAL SETUP AND IT IS WORTH SAYING SO PLAINLY: Changing the protocol midway means some patients received pemetrexed without the vitamins and some with them, and the difference in toxicity was seen within a single trial. At the same time this was not a randomised comparison of 'with vitamins' against 'without vitamins', so the strength of that particular finding differs from the strength of the trial's main result. We say this because the distinction matters: the direction is certain and has entered practice, but the trial did not measure the size of the benefit from supplementation itself as an endpoint.

THE SIGNAL FROM THE OTHER DIRECTION - WHAT HAPPENS WITHOUT SUPPLEMENTATION: In a retrospective analysis of patients given intrathecal pemetrexed for leptomeningeal disease, neutropenia occurred in about one third of patients, and a higher incidence and earlier onset were observed among those NOT receiving vitamin B12 and folic acid ^[3]. An important methodological caveat applies: the analysis covered 16 patients and 138 doses, it is retrospective, and the intrathecal route is off-label use. It is an observation consistent with the rest of the material, not a standalone proof. In a phase I/II study of the same route, folic acid and vitamin B12 supplementation was initiated BEFORE the first dose ^[4], reflecting the principle applied in intravenous regimens as well.

WHAT THIS ENTRY DOES NOT CONTAIN, AND WHY: We give no doses, no preparation forms and no timing. This is not an omission: the supplementation schedule is part of the medical prescription, depends on the specific protocol and on the patient's condition, and setting it out on an information page would be advice to an individual. The patient receives that schedule from the treating team along with the treatment itself.

WHAT MUST NOT BE READ INTO THIS ENTRY

• that folic acid 'helps in cancer' generally - the evidence presented concerns only patients treated with pemetrexed, and only the safety of that treatment;
• that an over-the-counter preparation replaces the schedule prescribed by the oncologist - starting, interrupting or altering supplementation during pemetrexed treatment on one's own may change the toxicity of that treatment;
• that this applies to other anticancer drugs - pemetrexed is a folate-pathway-targeting agent ^[2], and the whole relationship described here follows from that.

THE GENERAL RULE, WHICH APPLIES HERE TOO: The treating physician should be told about all supplements being taken, including those that seem harmless. Decisions about treatment and supplementation are made by the specialist physician. This page describes the state of knowledge and is not advice for any individual.

Sources

1. [1] Vogelzang NJ i wsp. — Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma, Journal of Clinical Oncology (dodanie kwasu foliowego i witaminy B12 po włączeniu 117 chorych; znamienne zmniejszenie toksyczności bez wpływu na przeżycie; mediana przeżycia 12,1 vs 9,3 miesiąca, p = 0,020): europepmc.org ↗
2. [2] Adverse events profiles of pemetrexed: a Food and Drug Administration Adverse Event Reporting System, Frontiers in Medicine 2026 (pemetreksed jako lek działający na szlak folianowy; najsilniejsze sygnały w zaburzeniach krwi i układu chłonnego, ROR = 7,31; znaczenie przestrzegania protokołu suplementacji): europepmc.org ↗
3. [3] Incidence of neutropenia with intrathecal pemetrexed for leptomeningeal disease associated with solid tumors — a retrospective analysis, Journal of Oncology Pharmacy Practice 2026 (16 chorych, 138 podań; większa częstość i wcześniejszy początek neutropenii u chorych bez suplementacji witaminą B12 i kwasem foliowym): europepmc.org ↗
4. [4] Intrathecal pemetrexed for newly diagnosed leptomeningeal metastases: a multicenter, open-label, phase I/II study, Journal of Neuro-Oncology 2025 (suplementację kwasem foliowym i witaminą B12 rozpoczynano przed pierwszą dawką): europepmc.org ↗

WHY THIS ENTRY EXISTS

Neuropathy after chemotherapy is one of those consequences of treatment for which medicine currently has least to offer — which is precisely why it is an area where patients most often reach for supplements on their own. Alpha-lipoic acid is among the most popular of them. This page describes what is known about it, not what anyone should do.

WHAT THE GUIDELINES SAY

• for the PREVENTION of chemotherapy-induced peripheral neuropathy, NO agent is recommended ^[1];
• the use of acetyl-L-carnitine for prevention of CIPN is explicitly discouraged ^[1];
• for TREATMENT of established painful neuropathy, duloxetine is the only agent with appropriate supporting evidence ^[1];
• alpha-lipoic acid is not among the recommended agents.

WHAT THE DATA ON ALA ITSELF SHOW

The MSKCC monograph records isolated reports suggesting ALA may be a useful adjunct in reducing paclitaxel-induced neuropathy, together with observations on doxorubicin cardiotoxicity and on salivary gland dysfunction and oral mucositis after radiotherapy ^[2]. These are results from small, single studies — not from registrational trials or reviews that would support a recommendation.

THE KEY WARNING — INTERACTION WITH CANCER TREATMENT: Alpha-lipoic acid may ANTAGONISE the effects of chemotherapy and radiotherapy because of its antioxidant properties ^[2]. This warning points in exactly the opposite direction from the hoped-for benefit, and it concerns the effectiveness of anticancer treatment rather than the patient's comfort. Deciding whether to use ALA during active treatment therefore requires assessment of the individual situation by the treating team and cannot be replaced by any general recommendation.

SEPARATELY — OTHER PRACTICALLY RELEVANT INTERACTIONS:

• ALA affects carbohydrate metabolism and may intensify the action of glucose-lowering drugs in people treated for diabetes;
• neuropathy in a cancer patient often has several causes at once (vitamin B12 deficiency, diabetes, alcohol, pressure from the tumour itself), so its assessment belongs to a physician — the symptom alone does not identify the cause.

WHAT THIS ENTRY DOES NOT SAY

We give no doses or dosing schedules, since that would be advice for an individual rather than a description of the state of knowledge. Nor do we claim that ALA does not work — we state that the evidence is limited and that alongside it stands a warning about possible weakening of treatment. Absence of high-quality evidence is not the same as evidence of absence, but during anticancer treatment the burden of that risk falls on the patient, not on the supplement.

THE DECISION BELONGS TO THE DOCTOR

Management of chemotherapy-induced neuropathy, and the taking of any supplements during cancer treatment, is decided by the treating specialist. All supplements being taken should be disclosed to the treating team — including those regarded as natural.

Sources

1. [1] Loprinzi CL i wsp. — Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol 2020 (PMID 32663120) — brak zalecanego środka w profilaktyce CIPN; acetylo-L-karnityna odradzana; duloksetyna jedynym lekiem z odpowiednimi dowodami w leczeniu bolesnej CIPN: europepmc.org ↗
2. [2] Memorial Sloan Kettering Cancer Center — About Herbs: Alpha-Lipoic Acid (pojedyncze doniesienia o zmniejszeniu neuropatii po paklitakselu; ostrzeżenie o możliwym antagonizowaniu chemioterapii i radioterapii): mskcc.org ↗

WHY PATIENTS REACH FOR IT

Echinacea is among the most widely bought herbal products, marketed for colds, flu, wound healing and "immune support" ^[1]. In oncology it is taken mainly by people whose white cell counts have been lowered by chemotherapy — precisely the situation in which the promise of "boosting the immune system" sounds most convincing. That intuition, rather than the herb itself, is the problem here.

WHAT THE EFFICACY TRIALS SHOWED

The evidence is mixed and limited. Memorial Sloan Kettering Cancer Center reports that echinacea was INEFFECTIVE in preventing the common cold caused by rhinoviruses ^[1]. On the other hand, one influenza trial found it as effective as oseltamivir, with fewer adverse events ^[1]. Neither line of evidence concerns cancer patients, and neither shows that the supplement repairs immunity damaged by chemotherapy — no such evidence exists.

WHY THIS IS NOT A NEUTRAL SUPPLEMENT IN ONCOLOGY.

• Some studies suggest echinacea could decrease plasma drug levels, affect therapeutic efficacy, or cause adverse effects with some anticancer drugs ^[1].
• Profound thrombocytopenia was reported in a lung cancer patient receiving cisplatin and etoposide, attributed to echinacea use ^[1].
• In laboratory studies echinacea inhibits CYP3A4 and CYP2C8 ^[1]. The thrombocytopenia seen with etoposide was thought likely to be due to CYP3A4 inhibition ^[1].
• The same mechanism works in the opposite direction: in vitro there is a risk of subtherapeutic systemic exposure of prodrugs such as tamoxifen, which must be metabolised to become active ^[1].
• Echinacea may antagonise the effects of immunosuppressants ^[1].

ADVERSE EFFECTS

Reported effects include headache, dizziness, nausea, constipation, gastrointestinal upset and rash ^[1]. More rarely: thrombotic thrombocytopenic purpura, acute hepatitis, acute liver failure, leukopenia and exacerbation of pemphigus vulgaris ^[1].

CONTRAINDICATIONS. Memorial Sloan Kettering lists: chemotherapy, autoimmune and allergic conditions, immunosuppression, and pregnancy or breastfeeding ^[1]. Note the apparent contradiction that is in fact consistent: a product said to stimulate the immune response is unsuitable both when the immune system attacks the body's own tissues and when it is being deliberately suppressed by drugs.

STRENGTH OF EVIDENCE

Limited. The efficacy trials concern respiratory infections in generally healthy people, give conflicting results, and do not transfer to a patient undergoing cancer treatment. The harm evidence rests on case reports and laboratory work on drug metabolism ^[1] — it does not allow the frequency of complications to be estimated, but it does establish that they are possible and involve drugs used in everyday oncology practice.

WHAT THIS ENTRY DOES NOT SAY

It neither recommends nor advises against anything for any individual, and gives no doses. It states what the trials showed and which interactions are documented. The decision to take or stop any supplement during chemotherapy belongs to the treating physician, who knows the full list of medicines taken.

SOURCES.

• ^[1] Memorial Sloan Kettering Cancer Center, About Herbs: Echinacea

Sources

1. [1] Memorial Sloan Kettering Cancer Center — About Herbs: Echinacea: mskcc.org ↗