Supplements

WHAT THE EVIDENCE SAYS

Selenium entered cancer-prevention research on the strength of observational data and a single 1990s trial in which reduced cancer incidence was a secondary, not a primary, endpoint ^[1]. The test came with SELECT (Selenium and Vitamin E Cancer Prevention Trial): 35,533 healthy men randomly assigned to selenium, vitamin E, both, or placebo ^[2]. No prevention of prostate cancer was found ^[2]. Moreover, the vitamin E arm showed a SIGNIFICANT INCREASE in prostate cancer risk — 620 cases versus 529 on placebo (HR 1.17; 99% CI 1.004–1.36; p = 0.008), that is 1.6 additional cases per 1,000 person-years (JAMA 2011) ^[2].

A nested analysis from the same trial (Journal of the National Cancer Institute 2014; 1,739 prostate cancer cases including 489 advanced, versus 3,117 comparison men) showed that the effect of supplementation DEPENDS ON BASELINE SELENIUM STATUS: in men with high baseline selenium, supplementation increased the risk of high-grade disease by 91% (p = 0.007), while in men with low selenium, vitamin E increased overall risk by 63% (p = 0.02) and high-grade risk by 111% (p = 0.008) ^[3]. The authors state the conclusion plainly: men should avoid selenium or vitamin E supplementation at doses exceeding recommended dietary intakes ^[3].

The 2018 Cochrane review (PMID 29376219) pooled the randomised evidence: no effect on overall cancer incidence (RR 1.01; 95% CI 0.93–1.10; 3 trials, 19,475 participants) and no effect on cancer mortality (RR 1.02; 95% CI 0.80–1.30; 1 trial, 17,444 participants) ^[1]. The absence of effect also held for individual sites: colorectal, lung, breast, bladder and prostate cancer ^[1]. The authors did, however, note signals of harm: increased melanoma risk in trials at low risk of bias, increased risk of type 2 diabetes, and more frequent alopecia and dermatitis ^[1].

STRENGTH OF THE EVIDENCE

High — and this is the key point here. This is not a topic where evidence is missing; on the contrary, the trials are large, randomised and long, and they agree: selenium supplementation does not reduce cancer risk ^[1]. Cochrane rates the certainty of that conclusion as high ^[1]. Continuing to look for benefit here is no longer a knowledge gap but a conclusion already drawn.

WHO THIS ENTRY IS FOR

For people considering selenium capsules as a way to prevent cancer or to support treatment, and for people after a diagnosis who encounter claims about the "anticancer action of selenium". This entry does not cover documented selenium deficiency diagnosed and treated by a physician — that is a clinical situation governed by its own rules and decided by the treating team.

INTERACTIONS WITH CANCER TREATMENT

Selenium is an antioxidant, and taking antioxidants during chemotherapy and radiotherapy is a matter of justified caution: both modalities work partly through oxidative damage to tumour cells ^[4]. The best available data come from a prospective observational study nested in the SWOG S0221 clinical trial (Journal of Clinical Oncology 2020, PMID 31855498; 1,134 breast cancer patients receiving chemotherapy) ^[4]. Use of any antioxidant supplement (vitamins A, C, E, carotenoids, coenzyme Q10) both before and during treatment was associated with numerically worse outcomes — recurrence adjHR 1.41 (95% CI 0.98–2.04) and death adjHR 1.40 (95% CI 0.90–2.18) — but THE CONFIDENCE INTERVALS INCLUDE 1.0, so for antioxidants alone this is not a statistically significant result and must not be presented as proof of harm ^[4]. What did reach significance in the same study were vitamin B12 (disease-free survival adjHR 1.83; 95% CI 1.15–2.92; overall survival adjHR 2.04; 95% CI 1.22–3.40) and iron taken during chemotherapy (recurrence adjHR 1.79; 95% CI 1.20–2.67) ^[4]. The authors advise caution with supplements other than multivitamins during chemotherapy ^[4].

There is also the question of dose itself: selenium in excess is toxic (selenosis — brittle hair and nails, hair loss, gastrointestinal and neurological symptoms), and the Cochrane review recorded an increased risk of type 2 diabetes in selenium groups ^[1]. The National Cancer Institute states the general rule without exceptions: "Tell your doctor if you're taking any dietary supplements, even vitamins, no matter how safe you think they are ^[5]."

THE SCOPE OF WHAT WE WRITE HERE

We give no doses and no blood-level thresholds, because that would be advice for an individual, and cancer3.ai is an information portal, not a clinic. We also do not cover intravenous selenium in hospital settings or the management of diagnosed deficiency — those are decisions for the treating team. We describe only what is known about selenium supplementation in relation to cancer risk and the course of oncological treatment.

Sources

1. Vinceti M et al. — Selenium for preventing cancer, Cochrane Database of Systematic Reviews 2018: europepmc.org ↗
2. Klein EA et al. — Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT), JAMA 2011: europepmc.org ↗
3. Kristal AR et al. — Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk, Journal of the National Cancer Institute 2014: europepmc.org ↗
4. Ambrosone CB et al. — Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221), Journal of Clinical Oncology 2020: europepmc.org ↗
5. National Cancer Institute — Complementary and Alternative Medicine (CAM), cancer.gov 2024: cancer.gov ↗

WHAT THE EVIDENCE SAYS

The starting point is a pharmacological difference that is rarely explained and that accounts for the whole dispute. Taken by mouth, plasma vitamin C is tightly controlled by absorption and renal excretion and does not exceed roughly 300 µM ^[1]. Intravenous administration bypasses that control and reaches concentrations of about 20 mM, tens of times higher (NCI PDQ) ^[1]. This means two things at once: studies of oral and intravenous vitamin C effectively concern two different interventions and conclusions must not be transferred between them; and reaching a high concentration is not itself evidence of clinical benefit — it is evidence that the drug arrived.

The clinical evidence is sparse and early. NCI lists phase I trials in pancreatic cancer (14 participants combined with gemcitabine and erlotinib; 9 participants with stage IV disease), a phase I/IIA trial in 27 patients with stage III/IV ovarian cancer, and more recent phase II trials in 47 patients with castration-resistant prostate cancer and 34 patients with stage IV pancreatic cancer ^[1]. These are small, mostly single-arm studies designed to assess safety and feasibility rather than efficacy ^[1]. A reported median overall survival of 12 months in pancreatic cancer means little without a comparison group — patients enrolled in early-phase trials are typically in better general condition than the average patient with that diagnosis ^[1].

The results are mixed and must be presented as such: some studies report fewer chemotherapy side effects and better quality of life, others show no anticancer effect at all ^[1][2]. Findings in cell cultures and animal models are considerably more promising than findings in humans — which in oncology is the rule rather than the exception and is not in itself an argument for use ^[1].

STRENGTH OF THE EVIDENCE

Low. There is not a single large randomised trial answering whether intravenous vitamin C prolongs life or delays progression ^[1]. Absence of evidence of benefit is not evidence of absence of benefit — but neither is it a basis for paying for a therapy presented as causal treatment. The regulatory position is unambiguous: the FDA has not approved IV vitamin C as a cancer treatment ^[1][2].

WHO THIS ENTRY IS FOR

For people who have been offered — usually privately, outside the public system — vitamin C infusions as part of cancer treatment, and for their families. It does not concern dietary vitamin C or the treatment of diagnosed deficiency (scurvy), which are separate matters entirely.

INTERACTIONS WITH CANCER TREATMENT

Plasma cell myeloma and bortezomib is the best-documented signal of harm. Vitamin C binds bortezomib and blunts its activity: in preclinical work, bortezomib combined with oral vitamin C produced greater tumour volume than bortezomib alone (NCI PDQ) ^[1]. Anyone treated with bortezomib should discuss any vitamin C supplementation with their physician.

A broader caution applies to all antioxidants taken during chemotherapy and radiotherapy, whose mechanism relies partly on oxidative damage to tumour cells. The best data come from an observational study nested in SWOG S0221 (JCO 2020; 1,134 breast cancer patients): antioxidant supplement use before and during chemotherapy was associated with numerically worse outcomes (recurrence adjHR 1.41; 95% CI 0.98–2.04), but the confidence interval includes 1.0, so this is NOT statistically significant and must not be presented as proof of harm ^[3]. What reached significance in that study were vitamin B12 and iron, not antioxidants ^[3].

CONTRAINDICATIONS — NO ROOM FOR UNDERSTATEMENT HERE

NCI lists them explicitly ^[1][2]. Glucose-6-phosphate dehydrogenase (G6PD) deficiency: high doses may cause haemolysis, and people with this inherited disorder should not be given them ^[1][2]. Kidney disease: kidney failure has been reported after treatment with IV vitamin C ^[2]. Predisposition to kidney stones: people likely to develop stones should not be treated with IV vitamin C ^[2]. Haemochromatosis and other iron-overload states: vitamin C increases iron absorption ^[2]. Outside these situations, infusions were generally well tolerated in clinical trials, with mild reported effects (increased urination, thirst, nausea, vomiting, chills) ^[1][2].

THE SCOPE OF WHAT WE WRITE HERE

We give no doses, infusion schedules or concentration targets — that would be advice for an individual, and cancer3.ai is an information portal, not a clinic. Nor do we rule on whether an infusion is acceptable alongside standard treatment in an individual case; that is for the treating team, which knows the diagnosis, renal function and the full medication list. We write about one thing: how strong the evidence is and where the known safety limits lie.

Sources

1. National Cancer Institute — Intravenous Vitamin C (PDQ®), Health Professional Version 2025: cancer.gov ↗
2. National Cancer Institute — Intravenous Vitamin C (PDQ®), Patient Version 2024: cancer.gov ↗
3. Ambrosone CB et al. — Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221), Journal of Clinical Oncology 2020: europepmc.org ↗

WHAT THE EVIDENCE SAYS

The starting point is solid and uncontested: gut bacteria help shape the response to immune checkpoint blockade ^[1][3]. The controversy begins with the practical question — whether that relationship can be exploited by swallowing a capsule.

The key clinical paper appeared in Science in 2021 (Spencer et al., PMID 34941392) ^[1]. It assessed faecal microbiota profiles, dietary habits and use of commercially available probiotic supplements in melanoma patients receiving immunotherapy, alongside parallel preclinical work ^[1]. The authors report: "Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use ^[1]." In mouse models the same picture was reproduced: a low-fibre diet or probiotic administration impaired the response to anti-PD-1-based therapy, with a lower frequency of interferon-gamma-positive cytotoxic T cells in the tumour microenvironment ^[1].

The picture is not uniform, however, and honesty requires the other side. A 2025 review (Frontiers in Immunology, PMID 41472726) collects data in which specific strains — Bifidobacterium, Lactobacillus, Clostridium butyricum, Akkermansia muciniphila — enhanced checkpoint inhibitor responses in animal models of melanoma, lung and colorectal cancer, while in early-phase clinical studies and retrospective cohorts, particularly in lung and renal cancer, probiotic use was associated with improved progression-free and overall survival ^[2]. The same authors state the limitation plainly: "most clinical data are observational, and the field lacks standardized probiotic formulations and dosing protocols ^[2]."

The second, far better established part of this topic is ANTIBIOTICS. The National Cancer Institute describes a European study as follows: "Patients who had taken antibiotics for an infection within 2 months before or 1 month after starting immunotherapy with checkpoint inhibitors did not live as long as patients who didn't take antibiotics ^[3]." A caveat must accompany that sentence: this is an observation, not an instruction to forgo antibiotics. Infection in a cancer patient can be life-threatening, and only the treating physician decides whether antibiotic therapy is warranted.

STRENGTH OF THE EVIDENCE

Low to moderate — and unevenly distributed. The association between microbiota composition and immunotherapy efficacy is well documented. The claim that taking a probiotic improves treatment outcomes is supported by NOT ONE conclusive randomised trial; the available clinical data are observational and therefore burdened by the fact that people who reach for supplements differ from those who do not in many ways at once ^[2]. Moreover, two good sources point in opposite directions — the Science paper signals possible harm, the 2025 review possible benefit ^[1][2]. In that situation the only honest answer is "we do not know", rather than picking whichever side sounds more agreeable.

WHO THIS ENTRY IS FOR

For patients treated with checkpoint inhibitors (most often in melanoma, lung cancer and renal cancer) and their families, who encounter reports that "the microbiome decides whether immunotherapy works" and wonder whether to buy a probiotic. It does not cover probiotics used for other indications under medical supervision, nor faecal microbiota transplantation, which remains an investigational procedure conducted only within clinical trials.

INTERACTIONS WITH CANCER TREATMENT

First — possible weakening of immunotherapy. The Science paper indicates that in melanoma patients taking probiotics the benefit of high fibre intake was less pronounced, and animal models showed an outright worse response to anti-PD-1 after probiotic administration ^[1]. This is a signal, not proof, but a signal pointing toward harm in a treatment that for many patients is the only effective option.

Second — infection risk. Probiotic strains are live microorganisms, and bloodstream infections caused by those very strains have been described in immunocompromised people ^[4][5]. A case series in Emerging Infectious Diseases (2024) on Clostridium butyricum bacteraemia after probiotic use noted that most patients had compromised immune systems ^[4]. In another series in the same journal (2026), among 5,034 children who received probiotics after cardiac surgery, 6 developed bacteraemia with a probiotic strain; all had central venous catheters ^[5]. The population differs from an oncological one, but the mechanism — translocation of live bacteria from the gut and catheter contamination — is the same, and patients on chemotherapy combine both risk factors: neutropenia and a vascular port. Saccharomyces fungaemia after administration of an S. boulardii preparation has also been described.

Third — antibiotics. As above: the association with shorter survival is documented, but the practical conclusion is "tell your treating team that you are starting immunotherapy", not "avoid antibiotics" ^[3].

WHAT THIS MEANS FOR DIET

The only element of this topic backed by clinical data suggesting benefit is DIETARY FIBRE from food, not a supplement from the pharmacy ^[1]. That is consistent with the catalogue entry on the Mediterranean diet, and the two entries are worth reading together.

THE SCOPE OF WHAT WE WRITE HERE

We give no strains, doses or regimens, because no standardised preparation of demonstrated efficacy exists, and naming a specific one would amount to advice for an individual ^[2]. We do not describe faecal microbiota transplantation beyond noting that it is investigational. cancer3.ai is an information portal — whether to take any supplement during cancer treatment is decided by the treating team.

Sources

1. Spencer CN et al. — Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response, Science 2021: europepmc.org ↗
2. Jani CT et al. — Leveraging beneficial microbiome-immune interactions via probiotic use in cancer immunotherapy, Frontiers in Immunology 2025: europepmc.org ↗
3. National Cancer Institute — Gut Bacteria Influence Effectiveness of a Type of Immunotherapy, Cancer Currents Blog 2018: cancer.gov ↗
4. Sada RM et al. — Clostridium butyricum Bacteremia Associated with Probiotic Use, Japan, Emerging Infectious Diseases 2024: europepmc.org ↗
5. Wang X et al. — Case Series of Bacteremia Associated with Probiotic Use in Children after Cardiac Surgery, China, Emerging Infectious Diseases 2026: europepmc.org ↗

WHAT THE EVIDENCE SHOWS

Beta-carotene is one of the few supplements assessed in large randomised trials rather than observational data alone — and both trials came out against supplementation ^[1][2].

• ATBC (New England Journal of Medicine 1994): 29,133 male smokers aged 50-69 from south-western Finland, beta-carotene 20 mg daily, five to eight years of follow-up ^[1]. Among 876 new lung cancer cases, the beta-carotene group had an 18% higher incidence and 8% higher total mortality, driven mainly by lung cancer and ischaemic heart disease ^[1].
• CARET (New England Journal of Medicine 1996): 18,314 smokers, former smokers and asbestos-exposed workers, beta-carotene 30 mg daily combined with 25,000 IU retinol ^[2]. The relative risk of lung cancer was 1.28 (95% CI 1.04-1.57; p=0.02), of death from any cause 1.17 (95% CI 1.03-1.33) and of death from lung cancer 1.46 (95% CI 1.07-2.00) ^[2]. The trial was stopped 21 months ahead of schedule ^[2].
• US Preventive Services Task Force (JAMA 2022): a grade D recommendation, that is, an explicit recommendation against beta-carotene supplements for the prevention of cancer or cardiovascular disease ^[3].

Both trials started from the opposite premise: epidemiological data linked carotenoid-rich diets and high serum beta-carotene with a LOWER risk of lung cancer ^[1][2]. A pharmacological-dose supplement did not reproduce that association — it reversed it ^[1][2]. This is the most frequently cited demonstration that a finding about dietary patterns does not transfer automatically to a pill.

WHO IS MOST CONCERNED

The harm signal comes from people who smoke and from workers exposed to asbestos, and it is best documented in those groups ^[1][2]. Trials of comparable size in never-smokers do not exist, which means "harm has not been demonstrated", not "safety has been demonstrated".

WHAT ABOUT BETA-CAROTENE FROM FOOD

These results concern supplements at doses far above dietary intake. They are not an argument against carotenoid-rich fruit and vegetables, which remain part of recommended eating patterns.

INTERACTIONS AND CAUTIONS DURING CANCER TREATMENT

• Beta-carotene is an antioxidant. The effect of high-dose antioxidants on the efficacy of radiotherapy and chemotherapy remains unresolved, and for that reason their routine use during treatment is not recommended.
• For people who smoke during cancer treatment, the documented increase in lung cancer incidence described above applies as well ^[1][2].
• The CARET regimen combined beta-carotene with retinol; that combination carries an additional risk of hypervitaminosis A ^[2].

A treating team can assess interaction risk only if it knows about every preparation being taken — a supplement left out of the history stays outside any control.

SCOPE OF THIS ENTRY

This entry covers beta-carotene supplements in an oncological context. It does not cover treatment of vitamin A deficiency or ophthalmological and dermatological uses, which follow separate indications.

Sources

1. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group — The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers, New England Journal of Medicine 1994: pubmed.ncbi.nlm.nih.gov ↗
2. Omenn GS et al. — Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease, New England Journal of Medicine 1996: pubmed.ncbi.nlm.nih.gov ↗
3. US Preventive Services Task Force — Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement, JAMA 2022: pubmed.ncbi.nlm.nih.gov ↗

WHAT THE EVIDENCE SAYS

The decisive study for this entry is MISTRAL (Palliative Medicine, July 2026): a phase 3, multicentre, randomised, double-blind, placebo-controlled trial in which 290 patients with advanced pancreatic cancer received standard treatment plus either subcutaneous mistletoe extract or placebo ^[1]. The primary focus was health-related quality of life, measured with the EORTC QLQ-C30 and QLQ-PAN26 questionnaires ^[1]. The result: no statistically significant differences between the arms in either quality of life or body weight ^[1]. In the nested biomarker study, the only significant change was a rise in eosinophils in the mistletoe group, with no clinical correlate; there were no differences in blood counts, lymphocyte subpopulations, C-reactive protein, albumin or Ca19-9 ^[1]. The authors' conclusion, verbatim: "Since no benefit was observed, there is no clinical reason to recommend mistletoe extract in patients with advanced pancreatic cancer ^[1]."

WHY WE PUT THIS SO PLAINLY WHEN OTHER SOURCES READ DIFFERENTLY.

This is a point where two credible sources diverge, and readers deserve to know what the difference rests on. The National Cancer Institute summary reports older work with mixed results: in pancreatic cancer, longer survival was described in people given mistletoe extract; in melanoma there was no increase in survival time; in lung cancer no differences were found ^[2]. We do not settle the contradiction by picking the more convenient sentence, but on methodological grounds. The earlier studies suggesting benefit in pancreatic cancer were neither blinded nor placebo-controlled, and in quality-of-life research that is decisive: a patient who knows they are receiving an "extra treatment" rates how they feel differently from one who does not ^[2]. MISTRAL tested precisely the setting in which the earlier data looked most promising, in a design immune to that effect, and found no benefit ^[1].

STRENGTH OF THE EVIDENCE

Moderate for the topic as a whole, high for one specific question. High: adding mistletoe to standard treatment in advanced pancreatic cancer does not improve quality of life — that comes from a large trial with the strongest available design ^[1]. Moderate for the rest: mistletoe preparations differ from one another (host tree species, manufacturer, method of preparation), they are used across many diagnoses and schedules, and most remaining data come from unblinded, small or observational studies ^[2]. This must not be read as "absence of effect has been proven in every cancer"; the correct statement is that where it has been tested most rigorously no benefit was shown, and elsewhere high-quality evidence is lacking.

WHAT READERS MAY NOT KNOW ABOUT HOW IT IS GIVEN.

Mistletoe in oncology is usually not a tablet or a tea. According to the National Cancer Institute, extracts are most often given by injection under the skin, and less commonly by mouth, into a vein, into the pleural cavity, or directly into a tumour ^[2]. This has two practical consequences. First, it is not a "dietary supplement" in the everyday sense and should not be thought of like a vitamin from the pharmacy. Second, reported side effects include soreness and inflammation at injection sites, headache, fever, chills, nausea and severe tiredness, and a few cases of severe allergic reactions, including anaphylactic shock, have been reported ^[2].

INTERACTIONS WITH CANCER TREATMENT

In the reference sources available to us there is no documented pharmacokinetic interaction between mistletoe and any specific anticancer drug — and we say so plainly rather than implying an interaction that has not been demonstrated ^[2][3]. The real problems lie elsewhere, and there are three.

• Fever, chills and injection-site inflammation can be mistaken for signs of infection. In a patient undergoing chemotherapy, particularly during neutropenia, fever is a state requiring urgent medical assessment — and a preparation that itself causes fever blurs that signal.
• Mistletoe extracts are immunologically active (MISTRAL recorded a rise in eosinophils) ^[1]. Data on combining them with modern immunotherapy, including checkpoint inhibitors, simply do not exist. Absence of data is not evidence of safety and should not be read as such.
• The risk of a severe allergic reaction, though rare, is real and independent of the cancer itself ^[2].

The general rule the National Cancer Institute states without exceptions: tell your doctor about every preparation you are taking, including those regarded as natural and safe ^[3].

THE SCOPE OF WHAT WE WRITE HERE

We give no doses, brand names or administration schedules, and we do not decide whether any individual should stop or continue mistletoe — that is a decision for their treating team, and cancer3.ai is an information portal, not a clinic. We describe the state of knowledge: what has been tested, how strong the test was, and what it showed.

Sources

1. Wode K et al. — Mistletoe extract in patients with advanced pancreatic cancer: Health-related quality of life in a double-blind, randomized, placebo-controlled trial (MISTRAL), Palliative Medicine 2026: europepmc.org ↗
2. National Cancer Institute — Mistletoe Extracts (PDQ®), Patient Version, updated 2023: cancer.gov ↗
3. National Cancer Institute — Complementary and Alternative Medicine (CAM), updated 2024: cancer.gov ↗

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 ↗

WHERE THE PROBLEM CAME FROM

Soy isoflavones (mainly genistein and daidzein) are structurally similar to oestrogens and weakly stimulate oestrogen receptors. Because most breast cancers are hormone-dependent, patients were for years advised against soy, and many women still avoid it. These concerns rested on cell-line and animal studies in which genistein abolished the inhibitory effect of tamoxifen on tumour growth ^[3].

WHAT PATIENT DATA SHOW

• a pooled analysis of four cohorts (two US, two Chinese), 9,514 patients, mean follow-up 7.4 years, 1,348 recurrences and 1,171 deaths, including 881 from breast cancer ^[1];
• intake of at least 10 mg of isoflavones per day versus the lowest intake: recurrence HR 0.75 (95% CI 0.61-0.92);
• death from breast cancer HR 0.83 (95% CI 0.64-1.07) - a favourable direction, but not significant;
• death from any cause HR 0.87 (95% CI 0.70-1.10) - also not significant;
• a 2025 review of the clinical and epidemiological evidence concludes that post-diagnosis isoflavone intake from food reduces the risk of recurrence and that observational data do NOT indicate interference with the efficacy of tamoxifen or aromatase inhibitors ^[2].

WHAT THESE RESULTS DO NOT SAY

All of the above come from observational studies, not randomised trials - they show an association, not causation. Women who eat a lot of soy may differ from others in lifestyle, body weight and access to care, and the analyses adjust only for what was measured. Only the recurrence result was statistically significant; these data do not settle the question of overall survival. Nor do the results say that soy treats breast cancer or that intake should be increased beyond customary amounts.

FOOD IS NOT THE SAME AS A SUPPLEMENT

The doses in the cited studies correspond to an ordinary diet (10 mg of isoflavones is roughly one serving of tofu, soy milk or edamame); the 2025 review speaks of at most two servings of traditional soy foods per day, about 50 mg of isoflavones ^[2]. Isoflavone preparations deliver many times higher doses in isolated form, for which safety data in breast cancer patients are lacking. Memorial Sloan Kettering puts it as follows: soy in food form is generally safe, whereas supplements or larger amounts of soy should be discussed with the treating team ^[3]. This is the same principle that applies to beta-carotene: the safety of a compound in vegetables does not transfer automatically to a tablet.

INTERACTIONS WITH CANCER TREATMENT

• tamoxifen - the signal of weakened activity comes from preclinical models (genistein abolishes growth inhibition of MCF-7 cells); the clinical relevance remains unknown and patient data do not confirm it ^[2][3];
• aromatase inhibitors - observational data do not indicate reduced efficacy ^[2];
• high-dose isoflavone supplements - MSKCC classes the use of soy in hormone-sensitive cancers as a controversial question and advises talking to a doctor before taking a preparation ^[3];
• separate issues are soy allergy and the effect of large amounts of soy on levothyroxine absorption - these are general medical, not oncological, questions.

WHAT THIS MEANS FOR THE READER

There is no basis today for a woman with breast cancer to eliminate ordinary soy foods from her diet for fear of recurrence - the data point rather in the opposite direction. Taking concentrated isoflavone preparations is not justified. Any supplementation during hormone therapy is a decision for the doctor leading the treatment.

Sources

1. [1] Nechuta SJ i wsp. — Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women, Am J Clin Nutr 2012 (n=9514, PMID 22648714): europepmc.org ↗
2. [2] Messina M, Nechuta S — A Review of the Clinical and Epidemiologic Evidence Relevant to the Impact of Postdiagnosis Isoflavone Intake on Breast Cancer Outcomes, Curr Nutr Rep 2025 (PMID 40131602): europepmc.org ↗
3. [3] Memorial Sloan Kettering Cancer Center — About Herbs: Soy (przegląd dowodów, interakcje z tamoksyfenem, ostrzeżenia): mskcc.org ↗

WHY THIS ENTRY EXISTS

Cannabis is among the most widely self-administered products used by people with cancer, and the information circulating outside medicine blends two entirely different claims: that it helps tolerate treatment, and that it treats the cancer. The first has partial support in evidence; the second has none ^[1][2]. That distinction is the substance of this entry.

SYMPTOMS: WHERE THE EVIDENCE IS STRONGEST. The 2024 American Society of Clinical Oncology (ASCO) guideline reviewed 13 systematic reviews and 5 additional primary studies ^[1]. The highest quality of evidence (moderate) was found for cannabinoids in refractory chemotherapy-induced nausea and vomiting, and specifically for licensed drugs rather than herbal cannabis ^[1].

• Dronabinol (synthetic THC) was approved for this indication in 1986 ^[2].
• Nabilone is a second available synthetic THC analogue ^[2].
• Nabiximols (Sativex, 1:1 THC:CBD) are approved in Canada for symptomatic relief of pain in advanced cancer ^[2].

For herbal cannabis itself, rigorous clinical trial data in these indications are lacking - what exists is largely patient surveys ^[2].

APPETITE AND WASTING

Here the picture is weaker than common belief suggests. Dronabinol's indication was extended in 1992 to anorexia associated with HIV infection, but clinical trials showed no statistically significant weight gain - patients did report improved appetite ^[2]. Improved hunger and weight gain are not the same thing, and in cancer cachexia it is the latter that counts (see the separate entry on nutrition in cachexia).

TREATING THE CANCER

NO DATA. The US National Cancer Institute PDQ summary states plainly that clinical trials of medicinal cannabis are limited and that the FDA has not approved cannabis as a treatment for any medical condition ^[2]. Evidence of antitumour activity comes exclusively from laboratory and animal work (apoptosis, inhibition of angiogenesis in glioma, breast and colorectal models) and has not been confirmed in humans ^[2]. On that basis the ASCO guideline strongly recommends against using cannabis or cannabinoids as cancer-directed treatment outside a clinical trial, citing very low quality evidence and poorer outcomes observed in patients using these products during immunotherapy ^[1].

INTERACTIONS WITH CANCER TREATMENT - THE ESTABLISHED PART

Cannabinoids interact with the hepatic cytochrome P450 enzyme system, through which a large share of anticancer drugs is metabolised ^[2]. The NCI warns that highly concentrated CBD oils could through this mechanism increase toxicity or decrease the effectiveness of treatment ^[2]. For a sense of scale: in a study of 24 patients receiving irinotecan or docetaxel, cannabis herbal tea did not significantly influence exposure to or clearance of these drugs ^[2] - so the risk concerns concentrated preparations above all, not every form of cannabis. The practical conclusion is single: cannabinoid use must be disclosed to the treating team, because without that information the interaction risk cannot be assessed.

INTERACTIONS WITH IMMUNOTHERAPY - THE CONTESTED PART

Here the data are outright contradictory and must be presented as such.

• The biological premise raises concern: THC produced immunosuppression and enhanced tumour growth in immunocompetent mice ^[2].
• The ASCO guideline cites poorer clinical outcomes in patients using cannabis during immunotherapy ^[1].
• Yet a pooled analysis of individual patient data from four Canadian Cancer Trials Group studies (684 patients on durvalumab plus tremelimumab, with or without chemotherapy; 65 patients, 9.5%, used cannabinoids and 32 did so at baseline) found no harm: immune progression-free survival was longer in cannabinoid users (10.91 versus 8.31 months; HR 0.60; 90% CI 0.36-1.00; p=0.05), overall survival did not differ significantly (14.23 versus 11.30 months; HR 0.81; 90% CI 0.51-1.27; p=0.35), and there were no differences in response rate or in immune-related adverse events ^[3]. The authors write that the finding supports the safe use of cannabinoids alongside combination immune checkpoint inhibitor therapy ^[3].

WHAT THESE DATA DO NOT SAY

The CCTG analysis is retrospective: dose, route and THC-to-CBD ratio were unknown, the number of users was small and most likely understated through under-reporting ^[3]. Most users had non-small cell lung cancer (41.5%) or pancreatic cancer (40.0%), so the result does not transfer automatically to other diagnoses ^[3]. A positive association between cannabinoid use and longer time to progression does NOT mean cannabinoids improve immunotherapy outcomes - they may simply not harm them, and the difference may reflect the characteristics of patients who reach for them. Nor did any of the cited studies examine whether cannabis affects survival under other treatment regimens.

WHAT THIS MEANS FOR THE READER

Cannabinoids in licensed drug form have a documented place in symptom control, above all in refractory nausea and vomiting ^[1][2]. They are not a cancer treatment and must not replace or delay cancer treatment ^[1][2]. Decisions on starting or continuing them, on the form of the preparation and on interaction risk belong to the physician managing the treatment, who knows the patient's full regimen.

Sources

1. Braun IM, Bohlke K, Abrams DI i wsp. — Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline, Journal of Clinical Oncology 2024;42(13):1575-1593: ascopubs.org ↗
2. National Cancer Institute — Cannabis and Cannabinoids (PDQ), Health Professional Version: cancer.gov ↗
3. Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data, Immunotherapy 2025 (PMID 40184324): pubmed.ncbi.nlm.nih.gov ↗

WHAT THE LARGEST TRIAL SHOWED

• a multicentre double-blind trial conducted in the URCC CCOP network; 576 patients entered the analysis (91% women, mean age 53) ^[1];
• patients were randomised to placebo or ginger at 0.5 g, 1.0 g or 1.5 g daily; the preparation was taken for 6 days, starting 3 days BEFORE chemotherapy ^[1];
• all participants received standard antiemetic treatment with a 5-HT3 receptor antagonist - ginger was studied as an ADDITION, never as a replacement ^[1];
• all ginger doses significantly reduced the severity of acute nausea on day 1 of chemotherapy compared with placebo (p=0.003); the largest reductions were at 0.5 g and 1.0 g (p=0.017 and p=0.036 respectively) ^[1];
• anticipatory nausea, arising before the drug was given, was an independent predictor of nausea (p<0.0001) ^[1].

STRENGTH OF EVIDENCE - MODERATE

MSKCC summarises the literature as mixed but generally supportive: ginger may reduce nausea and vomiting, while a systematic review pointed to the need for further confirmation and some studies showed no additional benefit when standard antiemetics were already in use ^[2]. The result is therefore not uniform: one large positive trial alongside a set of smaller studies with divergent outcomes.

WHAT THESE DATA DO NOT COVER

• the trial assessed ACUTE nausea on day 1; it is not evidence of efficacy in delayed nausea or in vomiting;
• the study population was 91% women and the abstract gives no breakdown by diagnosis, so transferring the result to any given cancer is extrapolation;
• there are no data here on any effect of ginger on the course of cancer, the efficacy of chemotherapy or survival.

INTERACTIONS AND SAFETY - THIS IS THE MOST IMPORTANT PART:

• BLEEDING: ginger inhibits thromboxane formation and platelet aggregation, and so significantly increases bleeding risk in people taking anticoagulant and antiplatelet drugs, including warfarin ^[2]. A fatal bleeding event has been reported in an elderly patient taking dabigatran after consuming a ginger and cinnamon mixture ^[2];
• SURGERY: because of bleeding risk, MSKCC advises stopping ginger 2 weeks before an operation ^[2];
• BLEEDING DISORDERS: a contraindication to use ^[2];
• OTHER DRUGS: potential interactions are described with non-steroidal anti-inflammatory drugs, insulin and tacrolimus ^[2];
• ADVERSE EFFECTS: most commonly heartburn and skin irritation ^[2];
• PREGNANCY: MSKCC advises avoiding it ^[2].

THE SCOPE OF WHAT WE WRITE HERE

We give the doses that WERE STUDIED, because they are part of describing the trial - this is not a dosing recommendation for an individual. Patients undergoing cancer treatment very often take anticoagulants (prophylaxis and treatment of venous thromboembolism is typical in oncology, not exceptional), have thrombocytopenia after chemotherapy, or are being prepared for surgery - in each of those situations the bleeding risk described above is real. Whether to take any plant preparation during treatment is decided by the treating physician, who should be told about ALL supplements being taken. This page describes the state of knowledge and is not advice for any individual.

Sources

1. [1] Ryan JL i wsp. — Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients, Supportive Care in Cancer 2012 (PMID 21818642): europepmc.org ↗
2. [2] Memorial Sloan Kettering Cancer Center — About Herbs: Ginger (podsumowanie kliniczne, działania niepożądane, interakcje z lekami przeciwkrzepliwymi): mskcc.org ↗

WHY PATIENTS REACH FOR IT

Sleep disturbance is among the most common and most overlooked problems in cancer - it accompanies treatment, anxiety, pain and hospital stays. Melatonin is available without prescription and widely assumed to be harmless, so it is often taken without the treating team knowing. That is precisely why this entry exists.

WHAT THE EVIDENCE SHOWS

• sleep and quality of life: in women after breast cancer treatment short-term supplementation improved sleep quality; improvement in subjective sleep quality has also been described in other patient groups ^[1];
• treatment side effects: data suggest a possible reduction in the incidence of thrombocytopenia, asthenia and neurotoxicity after chemotherapy, and of oral mucositis caused by chemo- and radiotherapy ^[1];
• fatigue, anxiety and mood: benefits have been described ^[1];
• survival: some trials report improvements in fatigue, quality of life and survival time, but the data are CONFLICTING and other work finds no benefit ^[1]. This point matters most here: melatonin is not to be treated as anticancer therapy.

STRENGTH OF EVIDENCE - MODERATE AND UNEVEN

The source's wording is consistently cautious (data suggest, has been described), and on survival it speaks explicitly of conflicting data ^[1]. Melatonin therefore stands as a supportive preparation of uncertain effect size, not an established part of supportive care.

ADVERSE EFFECTS

Drowsiness, headaches, altered mental status, tachycardia, hypothermia ^[1]. Driving should be avoided until the individual response is known ^[1]. A SEPARATE PAEDIATRIC WARNING: in children under 3 years, trouble breathing and deaths have been reported, and serious outcomes have been described in ingestion cases ^[1].

INTERACTIONS WITH TREATMENT - THE PART THAT MUST NOT BE OMITTED:

• HORMONE-SENSITIVE CANCERS: MSKCC lists breast and prostate cancer as a contraindication, because melatonin can change the amount of oestrogen in the body ^[1];
• ANTICOAGULANTS: melatonin is associated with lower plasma levels of factor VIII and fibrinogen, increasing bleeding risk ^[1];
• CYP1A2: melatonin inhibits this enzyme and may increase the bioavailability of substrate drugs (the example given by the source is fluvoxamine) ^[1];
• IMMUNOSUPPRESSANTS: risk of exacerbating myasthenia gravis ^[1];
• NIFEDIPINE: elevations in blood pressure and heart rate have been described ^[1].

THE SCOPE OF WHAT WE WRITE HERE

We give no doses or timing - that would be advice for an individual. We do draw attention to a situation typical in oncology: a patient with breast or prostate cancer, on hormonal treatment and thromboprophylaxis, meets TWO separate warnings here at once. Whether to take melatonin during cancer treatment is decided by the treating physician, who should be told about all preparations being taken, including those available without prescription. This page describes the state of knowledge and is not advice for any individual.

Sources

1. [1] Memorial Sloan Kettering Cancer Center — About Herbs: Melatonin (podsumowanie kliniczne, działania niepożądane, interakcje lekowe, przeciwwskazania w nowotworach hormonozależnych): mskcc.org ↗

WHY PEOPLE REACH FOR IT

Green tea is a beverage, not a drug, and that is precisely why its extract feels like a risk-free choice. Preparations standardised for epigallocatechin gallate (EGCG) are sold over the counter as antioxidants and weight-loss support ^[1]. A patient drinking a few cups a day and a patient taking an extract capsule are in two different situations — and that distinction is the core of this entry.

WHAT THE ONCOLOGICAL EVIDENCE SHOWS — SIGNALS IN BOTH DIRECTIONS:

• prevention: data are mixed, with possible benefit suggested for oral premalignant lesions and in populations at high risk of liver and colorectal cancer ^[1];
• prostate cancer: a blend containing green tea showed protective effects after treatment, but high-dose combination supplementation was associated with an ELEVATED incidence of prostate cancer in high-risk men ^[1]; long-term EGCG did not prevent recurrence ^[1];
• breast cancer: reduced recurrence risk has been reported, but regular consumption may elevate risk in some postmenopausal women ^[1];
• ovarian cancer: EGCG did not prevent recurrence ^[1];
• treatment side effects: limited data indicate EGCG may reduce radiation-induced oesophagitis in lung cancer patients and radiation dermatitis ^[1].

WHAT FOLLOWS FROM THIS PICTURE

This is not the profile of a preparation with proven anticancer activity. It is the profile of a substance whose effect depends on dose, formulation and clinical setting, and which in part of the research turned out opposite to expectation.

INTERACTIONS WITH CANCER TREATMENT — THE MOST IMPORTANT PART:

• BORTEZOMIB and other boronic acid-based proteasome inhibitors: EGCG and other polyphenols can inhibit their therapeutic effect ^[1]. This concerns the backbone of multiple myeloma treatment, so the supplement may reduce the efficacy of therapy;
• IRINOTECAN: EGCG inhibits biliary elimination, prolongs half-life and increases the risk of toxicity ^[1];
• PALBOCICLIB: decreased bioavailability in animal models ^[1];
• TAMOXIFEN: increased oral bioavailability, although a clinical trial did not confirm the interaction ^[1];
• NINTEDANIB: 21% reduction in bioavailability ^[1];
• anticoagulants and antiplatelet drugs: vitamin K antagonism at high intake ^[1];
• CYP3A4 and UGT substrates, verapamil, nadolol, rosuvastatin and atorvastatin — documented changes in drug exposure ^[1].

SAFETY: Common effects are nausea, stomach pain, sleep disruption and headache ^[1]. The serious concern is liver injury: hepatotoxicity has been documented at doses from 800 mg EGCG daily, with case reports of jaundice and acute hepatitis after green tea extracts ^[1]. At high doses (800–1600 mg EGCG daily) elevated liver enzymes, rectal bleeding and indigestion have also been described ^[1]. MSKCC lists contraindications: pregnancy and breastfeeding, stomach ulcers, and use on an empty stomach; the preparation should be discontinued if liver symptoms develop ^[1].

WHAT THIS ENTRY DOES NOT SAY

We give no doses and no regimen — any decision about a supplement during cancer treatment belongs to the treating physician, who knows the regimen and the patient's liver status. Nor do we claim that green tea as a drink is harmful: the reported liver events and most interactions concern concentrated EXTRACTS, not an ordinary infusion.

WHAT TO TELL THE TREATING TEAM

That an extract is being taken, the EGCG dose stated on the packaging, and every other supplement — especially before starting bortezomib, irinotecan or the targeted agents listed above.

Sources

1. [1] Memorial Sloan Kettering Cancer Center — About Herbs: Green Tea (dowody kliniczne, hepatotoksycznosc od 800 mg EGCG na dobe, interakcje z bortezomibem, irynotekanem, palbocyklibem, tamoksyfenem i nintedanibem): mskcc.org ↗

WHERE THE QUESTION COMES FROM

The reasoning that leads a patient to the vitamin shelf is logical and not at all naive: cancer treatment also damages healthy cells, and antioxidants protect cells from oxidative damage, so they ought to reduce collateral harm. NCI describes this motivation directly: antioxidants are taken by many cancer patients because it is thought that the substances will protect and repair healthy cells damaged by cancer therapy ^[1].

WHERE THAT REASONING BREAKS DOWN

Numerous anticancer agents generate reactive oxygen species, which decrease antioxidant levels, damage DNA and cause cancer cell death ^[1]. This is not a side effect of treatment — it is its MECHANISM. A preparation that blunts that mechanism may therefore blunt the treatment itself. The very property meant to protect a healthy cell also protects a cancer cell, and the supplement does not tell one from the other.

WHAT THE TRIALS SHOWED — HEAD AND NECK CANCER: Two randomised controlled trials assessed alpha-tocopherol (vitamin E) at 400 IU daily during radiation therapy ^[1]. The results:

• higher risk of tumour relapse,
• increased all-cause mortality,
• a decrease in cancer-free survival ^[1].

These are randomised trials, the strongest form of evidence available on this question, and they point to HARM rather than to absence of benefit.

WHAT THE STUDIES SHOWED — BREAST CANCER:

• a 2019 study: postmenopausal breast cancer survivors using antioxidant supplements (selenium, multivitamins, zinc, vitamins A, C and E) during chemotherapy or radiation had an increased risk of total mortality and worsened recurrence-free survival ^[1];
• a 2020 study: use of antioxidants (vitamins A, C, E; carotenoids; coenzyme Q10) during treatment with cyclophosphamide, doxorubicin and paclitaxel was associated with an increase in the hazards of recurrence and death; the result was not statistically significant but trended in the same direction as the previous one ^[1].

Both are observational and therefore do not establish causation — their value lies in independently pointing the same way as the randomised trials.

HOW NCI SUMS IT UP

This evidence gives reason to use these supplements with caution and indicates that more research on this topic is needed ^[1]. For many specific antioxidant supplements there is insufficient information to determine whether they are safe and effective ^[1].

WHAT THIS ENTRY DOES NOT SAY

• it does not concern antioxidants present in FOOD. Vegetables and fruit supply the same compounds in incomparably smaller amounts and in a different form; the problem described here concerns concentrated preparations;
• it does not concern preparations taken to correct a documented DEFICIENCY, for example in anaemia or proven vitamin D deficiency — that is a separate clinical situation decided by a physician;
• it contains no recommendation for any individual and gives no doses. The decision to stop or continue a supplement during treatment belongs to the treating physician.

WHAT TO TELL THE TREATING TEAM

About every vitamin or mineral preparation being taken, with the dose stated on the packaging — including multivitamins, which are rarely reported because they are not thought of as medicines. A conversation before chemotherapy or radiotherapy begins is a cheaper solution than stopping a preparation halfway through treatment.

Sources

1. [1] National Cancer Institute — Cancer Therapy Interactions With Foods and Dietary Supplements (PDQ), Health Professional Version (mechanizm reaktywnych form tlenu; dwa badania z losowym doborem z alfa-tokoferolem 400 j.m. w nowotworach glowy i szyi; prace Jung 2019 i Ambrosone 2020 w raku piersi; stanowisko o ostroznosci): cancer.gov ↗

WHAT LAETRILE IS

Laetrile is a purified form of amygdalin, a cyanogenic glycoside found in the pits of many fruits and in raw nuts ^[1]. It is sometimes sold as vitamin B17, although no vitamin classification recognises that designation ^[1]. The cyanide released from the molecule is regarded by advocates of the preparation as its principal anticancer component ^[1].

WHAT THE CLINICAL TRIAL SHOWED

The decisive data come from an NCI-sponsored phase II trial that enrolled 179 patients with various cancers, predominantly of the breast, colon and lung ^[1]. Among the 178 treated patients:

• ONE patient met response criteria, with a partial response lasting 10 weeks ^[1];
• 54% had measurable disease progression by the end of the intravenous course ^[1];
• seven months after completing therapy, ALL patients had disease progression ^[1];
• 7% reported improved work capacity and 20% reported symptomatic relief, but that relief did not persist ^[1].

Laetrile has shown little anticancer activity in animal studies and none in human clinical trials ^[1].

WHY THE ROUTE OF ADMINISTRATION CHANGES THE RISK

Cyanide is released from the molecule only under the action of beta-glucosidase enzymes, present in intestinal bacteria and in some commonly eaten plants ^[1]. Blood cyanide levels were therefore not elevated after intravenous administration but were elevated after oral therapy, and poisoning occurs far more frequently with oral use ^[1]. In animal studies, germ-free rats showed no effects from oral laetrile, whereas animals with normal gut flora showed signs of cyanide poisoning including lethargy and convulsions ^[1].

INTERACTIONS THAT INCREASE THE DANGER

Toxicity rises with concurrent consumption of ^[1]:

• raw almonds and crushed fruit pits,
• foods containing beta-glucosidase: celery, peaches, bean sprouts, carrots,
• high-dose oral vitamin C.

A case of life-threatening cyanide toxicity following ingestion of amygdalin together with vitamin C has been reported ^[1]. This combination is particularly troubling because both substances tend to be taken by the same people, as two elements of a single self-treatment strategy — precisely where the risk is greatest.

WHAT POISONING LOOKS LIKE

Adverse effects mirror the picture of cyanide poisoning: nausea, vomiting, headache, dizziness, liver damage, low blood pressure, fever, ataxic neuropathies, drooping eyelids, mental confusion, coma and death ^[1].

LEGAL STATUS

Laetrile is not approved for use in the United States; in 1980 the Supreme Court upheld a federal ban on interstate shipment ^[1]. It continues to be manufactured and administered, mainly in Mexico and in some clinics in the United States ^[1].

WHAT THIS ENTRY DOES NOT SAY

It is not a recommendation for any individual, nor a judgement on decisions already taken. Anyone taking laetrile, or considering taking it, should tell their treating physician — not least because the symptoms of cyanide poisoning can be mistaken for side effects of cancer treatment, and telling them apart determines what is done next. Decisions about cancer treatment are made by the specialist physician.

Sources

1. National Cancer Institute — Laetrile/Amygdalin (PDQ) Health Professional Version: cancer.gov ↗

WHAT SELECT TESTED

SELECT (the Selenium and Vitamin E Cancer Prevention Trial) was a large randomised trial designed to test whether vitamin E and selenium PREVENT prostate cancer ^[1]. More than 35,000 men aged 50 and over took part, assigned to receive vitamin E at 400 IU per day, selenium, both together, or placebo ^[1]. Mean follow-up was seven years: 5.5 years on supplements and a further year and a half of observation after they were stopped ^[1].

A RESULT OPPOSITE TO THE ONE INTENDED

The trial was designed to demonstrate benefit and demonstrated harm. In the group taking vitamin E alone, 76 prostate cancers were diagnosed per 1,000 men versus 65 per 1,000 on placebo — a relative increase of 17% ^[1]. The NCI states that this difference is statistically significant ^[1].

THE RISK DID NOT DISAPPEAR WHEN THE SUPPLEMENT STOPPED. The most important practical observation concerns not the increase itself but its persistence: the number of diagnoses continued to rise during the year and a half after men stopped taking vitamin E ^[1]. The effect therefore cannot be undone simply by stopping the supplement at the moment concern arises — which is an argument against starting high doses without an indication.

WHAT ABOUT SELENIUM

Men taking selenium alone, and selenium together with vitamin E, were also diagnosed with prostate cancer more often than the placebo group, but those differences were smaller and did not reach statistical significance ^[1]. This is therefore not evidence that selenium protects against the adverse effect of vitamin E — it is an absence of a finding, and the two are not the same thing.

WHAT THESE DATA DO NOT SAY

They do not say that vitamin E in food is harmful; the trial studied a supplement at a dose many times dietary intake ^[1]. Nor do they say anything about the management of someone already diagnosed with cancer, or about patients given vitamin E for a documented deficiency or fat malabsorption — those are separate situations decided by the treating physician. The SELECT result concerns men without a cancer diagnosis taking a high-dose preparation to prevent disease. This entry gives no doses or schedules, as that would be advice for an individual.

Sources

1. National Cancer Institute — Selenium and Vitamin E Cancer Prevention Trial (SELECT): Questions and Answers: cancer.gov ↗

WHAT IT IS AND WHY IT CONCERNS ONCOLOGY

St John's wort is a herb used for mild to moderate low mood, sold over the counter as capsules, tablets and infusions. It appears in this catalogue not because it has antitumour activity, which has not been demonstrated, but because it is one of the best documented herbs causing drug interactions. The indication for which people take it overlaps with a common experience during cancer treatment, so the risk of concurrent use is real rather than theoretical.

MECHANISM OF THE INTERACTION

St John's wort induces the CYP3A4 enzyme in the liver and the membrane transporter P-glycoprotein ^[1]. Both systems clear drugs from the body. Inducing them means a drug is broken down and excreted faster, so its blood level is lower than assumed when the dose was set. The direction of this interaction runs against everyday intuition: the problem is not overdose but LOSS OF TREATMENT EFFICACY.

WHAT HAS BEEN MEASURED IN PEOPLE

• Irinotecan (used among others in colorectal cancer): in a crossover study in 5 cancer patients taking St John's wort 300 mg three times daily for 18 days, plasma levels of the active metabolite SN-38 fell by 42%, and markedly deeper suppression of bone marrow function was described alongside it ^[1][2].
• Imatinib: in two independent studies enrolling 12 and 10 subjects, at the same herb dose for 14 days, the area under the concentration curve, the maximum concentration and the half-life all decreased; the estimated magnitude is a 30-40% reduction in drug exposure ^[1].

WHY THIS IS MORE DANGEROUS THAN IT LOOKS

The interaction does not produce a new complaint the patient could report — only a silent fall in drug levels. Neither the patient nor the treating team has a symptom prompting them to look, unless the herb is asked about directly. St John's wort is also often regarded as harmless precisely because it is natural and sold without prescription, so it frequently goes unmentioned when medication is reviewed.

HOW LONG THE EFFECT LASTS AFTER STOPPING

Enzyme induction does not stop overnight. CYP3A4 activity returns to baseline roughly one week after St John's wort is discontinued, with an estimated half-life of this effect of about 46 hours ^[1]. Stopping the herb on the day the drug is given therefore does not remove the problem.

LIMITS OF THE EVIDENCE, STATED PLAINLY. The studies in cancer patients are SMALL: five people in the irinotecan study, ten and twelve in the imatinib studies. Groups that size cannot tell us how large the fall in drug levels will be in any individual, or in whom it will be greatest. What is strong is the MECHANISM itself and its direction, confirmed across many drugs and not only anticancer ones. Herbal preparations also vary in active content between manufacturers, so the potency of one package need not match another.

SCOPE OF THIS ENTRY

This entry describes a documented pharmacological phenomenon and contains no recommendations for any individual and no management schedules. Decisions about what to take and what to stop during cancer treatment belong to the treating physician, who knows the full medication list. The one point that matters for the reader: taking St John's wort or other herbal preparations is worth telling the treating team about, because without that information the interaction cannot be anticipated.

Sources

1. Borrelli F, Izzo AA. Herb-Drug Interactions with St John's Wort (Hypericum perforatum): an Update on Clinical Observations. AAPS Journal 2009 (przeglad; PMC2782080): pmc.ncbi.nlm.nih.gov ↗
2. Mathijssen RHJ i wsp. Effects of St John's wort on irinotecan metabolism. Journal of the National Cancer Institute 2002 (PMID 12189228): pubmed.ncbi.nlm.nih.gov ↗

WHY PEOPLE TAKE IT

Silymarin, a mixture of flavonolignans from milk thistle seeds, has a firm reputation as a liver-protective agent. Patients most often start it on their own initiative when liver function tests rise during chemotherapy ^[1].

WHAT THE EVIDENCE SHOWS

Memorial Sloan Kettering summarises the data cautiously: these are SMALL studies rather than decisive clinical trials ^[1]. They suggest:

• reduced chemotherapy-induced liver injury in children with acute lymphoblastic leukaemia and in patients with non-metastatic breast cancer,
• reduced radiotherapy-induced mucositis in patients with head and neck cancer,
• reduced chemotherapy-induced peripheral neuropathy and hand-foot syndrome (oral and topical forms),
• benefit in radiodermatitis in patients with breast cancer (topical form).

What the evidence does NOT show: silymarin does not treat cancer, does not replace any part of oncological treatment, and there are no data that it improves survival.

INTERACTIONS WITH CANCER TREATMENT

This is the most important part of this entry:

• milk thistle INHIBITS cytochrome CYP3A4, the enzyme that metabolises a large share of anticancer drugs, and can therefore change their concentrations ^[1];
• it modulates UGT enzymes, which per MSK may increase side effects of drugs metabolised by that route ^[1];
• it may decrease the clearance of sirolimus ^[1];
• a case of INR rising from 2.64 to 4.12 was reported in a patient on warfarin ^[1];
• cases of pancreatitis were reported with concomitant haloperidol or risperidone ^[1].

CONTRAINDICATIONS AND ADVERSE EFFECTS

Do not use if allergic to plants of the daisy/ragweed family. At high doses, increases in bilirubin and liver enzymes have been described — the opposite of the expected effect. Cutaneous reactions have also been reported: pruritus, rash, urticaria ^[1].

WHAT THIS MEANS

A supplement that looks like a neutral herbal add-on sits directly on the metabolic pathway of cancer drugs. Whether to take it during treatment is decided by the treating physician, who knows the full medication list. This entry is not medical advice.

Sources

1. Memorial Sloan Kettering Cancer Center — About Herbs: Milk Thistle: mskcc.org ↗

WHY PEOPLE TAKE IT

Reishi (lingzhi) is the best known of the so-called medicinal mushrooms, sold as an “immune-boosting” product and as “support during cancer”. It comes as powder, capsules and spore extracts ^[1].

WHAT THE EVIDENCE SHOWS

Memorial Sloan Kettering summarises the data as SMALL clinical studies in which reishi increased plasma antioxidant capacity and affected immune and tumour responses ^[1]. That is not enough to claim efficacy: there is no evidence that reishi treats cancer, prolongs survival, or replaces any part of oncological treatment. MSK also notes findings in the opposite direction — a reishi extract showed toxic effects in leukocytes ^[1].

A SIGNAL THAT MUST NOT BE OVERLOOKED

Patients undergoing treatment for gastrointestinal cancer who took reishi spore supplements had HIGHER levels of the tumour marker CA72-4 ^[1]. In practice this means the supplement may distort the follow-up tests the physician uses to judge how treatment is going.

INTERACTIONS WITH CANCER TREATMENT

• anticoagulants and antiplatelet drugs — reishi can increase bleeding risk ^[1];
• immunosuppressants — reishi enhances the immune response, working against the purpose of such treatment ^[1];
• drugs metabolised by cytochrome P450 — in vitro, reishi polysaccharides inhibited CYP2E1, CYP1A2 and CYP3A ^[1].

SAFETY. Cases of liver injury after powdered reishi have been reported, including one DEATH from fulminant hepatitis ^[1]. Reported adverse effects include nausea, insomnia, dry mouth, constipation, pruritus and vertigo ^[1].

WHAT THIS MEANS

“Natural” and “immune-boosting” does not mean neutral for treatment. Any decision about taking a mushroom preparation 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: Reishi Mushroom: mskcc.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 PEOPLE TAKE IT

Coenzyme Q10 (ubiquinone) is involved in cellular respiration and energy production ^[1]. It is sold mainly for heart disease, high cholesterol, statin-induced muscle pain, migraine, Parkinson's disease and infertility ^[1]. In oncology it is often bought by patients receiving anthracyclines — out of concern for the heart — and by people looking for a remedy for fatigue.

WHAT THE EVIDENCE SHOWS IN CANCER PATIENTS

The most important signal for patients is a warning, not an encouragement: antioxidant supplementation including CoQ10 before and during treatment was associated with an INCREASED hazard of recurrence in breast cancer patients ^[1]. In patients on tamoxifen, CoQ10 appeared to lower inflammatory cytokine levels ^[1], but that is a biological result, not proof of clinical benefit. Preliminary studies on cancer-related fatigue are MIXED ^[1]. Protection against doxorubicin toxicity was described in a murine model ^[1] — that is, not in humans.

WHY “ANTIOXIDANT” IS NOT AN ADVANTAGE HERE. Radiotherapy and some chemotherapy act partly through oxidative stress. For this reason MSK states plainly that CoQ10's antioxidant properties may REDUCE the effectiveness of chemotherapy and radiation therapy ^[1]. This is the same concern that applies to antioxidant supplements as a class.

INTERACTIONS WITH CANCER AND OTHER TREATMENT

• chemotherapy and radiotherapy — possible reduction in treatment effectiveness due to antioxidant activity ^[1];
• warfarin — CoQ10 may antagonise its anticoagulant effect ^[1];
• increased bleeding risk has also been reported ^[1].

SAFETY. Adverse effects are infrequent: nausea, diarrhoea and appetite suppression ^[1].

WHAT THIS MEANS

A product bought “to protect the heart” during chemotherapy may work against the treatment, and in breast cancer patients a higher hazard of recurrence was described with antioxidant supplementation. 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: Coenzyme Q10: mskcc.org ↗

WHERE THE DEFICIENCY COMES FROM

Niacin (vitamin B3) is obtained not only from food but also from tryptophan, an amino acid supplied with dietary protein. Neuroendocrine tumours causing carcinoid syndrome divert tryptophan elsewhere: they consume it to produce serotonin. When the tumour takes up a large share of the tryptophan pool, the substrate for niacin synthesis may run short - this is the mechanism of deficiency described in the European guidelines ^[1]. The extreme form of that deficiency is pellagra, classically described as a triad: skin lesions, diarrhoea and cognitive disturbance ^[1].

WHAT THE EVIDENCE SHOWS

A 2018 review of carcinoid syndrome brings together figures that are worth reading side by side, because they describe two different things. Full clinical pellagra is rare - "usually<1%, but up to 3% in one study" of patients ^[2]. When niacin was actually measured, however, deficiency proved far more common: in one study it affected 10 of 36 patients, that is 28% ^[2]. Among 42 supplemented patients, niacin levels normalised, and before supplementation urinary niacin metabolites were below normal in 45% of those tested ^[2].

Put differently: symptomatic pellagra is uncommon in this disease, but biochemical deficiency - invisible without testing - is frequent.

STRENGTH OF EVIDENCE

Limited. All the figures quoted come from small patient series and review articles, not from randomised controlled trials ^[2]. There is no study comparing supplementation with no supplementation in terms of survival, quality of life or complication rates. What is documented is that supplementation normalises niacin levels ^[2] - an effect on a laboratory measure, not on hard endpoints. The mechanism of tryptophan depletion, by contrast, is well described and consistently presented in society guidelines ^[1].

INTERACTIONS WITH CANCER TREATMENT

Two points matter in practice.

The first concerns somatostatin analogues, the mainstay of symptomatic treatment in carcinoid syndrome. The ENETS guidelines state that in patients previously treated with somatostatin analogues, deficiencies of fat-soluble vitamins should be looked for and adequately substituted ^[1]. Cancer treatment therefore changes nutritional status itself and can be a reason for monitoring, not merely a background factor.

The second concerns the form and dose of the vitamin. The literature describes nicotinamide at 250-500 mg per day orally for treating deficiency ^[3], whereas high doses of niacin (of the order of 3000 mg per day) may cause flushing, jaundice, impaired vision and abdominal discomfort, and sustained high doses may cause liver injury ^[3]. The tolerable upper intake level for adults is 35 mg per day ^[3]. In carcinoid syndrome this carries extra weight: flushing is the most prevalent symptom of the disease itself, reported in approximately 85% of patients ^[4]. A drug-induced symptom may therefore be mistaken for the disease or for its exacerbation - and vice versa. This is one reason why the choice of preparation and dose is not a neutral matter and belongs to the physician.

WHAT THIS ENTRY DOES NOT SAY

It does not say that every patient with a neuroendocrine tumour should take vitamin B3, nor what dose is appropriate in an individual case. The figures quoted describe groups of patients studied in the literature, not a recommendation for one person.

WHAT TO DISCUSS WITH THE TREATING TEAM

Whether, in a given situation, it is reasonable to check nutritional status and vitamin sufficiency - particularly during long-term somatostatin analogue treatment ^[1], chronic diarrhoea, or skin and cognitive symptoms that could correspond to the described triad ^[1]. Diagnosing a deficiency requires testing, and diagnostic and therapeutic decisions are made solely by a specialist physician.

WHY THIS ENTRY EXISTS

A low haemoglobin level is popularly equated with iron deficiency, and iron products are among the most commonly bought without prescription. In bone marrow disorders the mechanism differs: the marrow fails to produce normal cells even though the body is not short of iron.

WHAT THE SOURCE SAYS

In its summary on myelodysplastic syndromes NCI describes that anaemia is treated with red-cell transfusions to avoid symptoms, and that the oral iron-chelating agent deferasirox has come into widespread use. Chelation is the REMOVAL of iron from the body, used precisely because repeated transfusions accumulate it.

HOW STRONG IS THE EVIDENCE

NCI states explicitly that while some consensus panels advocate prophylactic iron chelation in patients with ongoing transfusion needs, the impact of chelation on survival and disease progression is unknown. The honest conclusion is therefore limited: iron accumulation itself is certain, the benefit of treating it is not.

WHAT THIS MEANS FOR THE READER

• A blood count is not enough to diagnose iron deficiency; iron studies, including ferritin, serve that purpose.
• Iron deficiency can coexist with cancer, for instance with gastrointestinal bleeding, and then iron treatment may be justified. This entry does not claim iron is always harmful; it says it must not be chosen on one's own.
• Multi-ingredient and "strengthening" preparations often contain iron, which is easy to overlook. It is worth showing the package to the physician.
• Supplementation, its dose and any chelation are decided by the haematologist in charge of treatment.

WHAT THIS ENTRY IS ABOUT

Oral mucositis is the painful inflammatory reaction that develops during radiotherapy to the head and neck region and during some chemotherapy regimens, and it can make eating impossible. It is among the most common and most burdensome complications of treatment in this region; a scoping review of 151 studies on the oral consequences of irradiation lists, alongside mucositis, dental caries, periodontitis, xerostomia, candidiasis, trismus, dysphagia and osteoradionecrosis ^[4].

WHAT THE GUIDELINES SAY

• MASCC/ISOO (the Multinational Association of Supportive Care in Cancer with the International Society of Oral Oncology) reviewed 78 papers, of which 49 entered the analysis, and made a NEW SUGGESTION in favour of honey delivered topically COMBINED with systemic delivery, for the PREVENTION of oral mucositis in head and neck cancer patients receiving radiotherapy with or without chemotherapy ^[1];
• in the same paper, for the remaining interventions in the "natural and miscellaneous agents" group — herbal compounds, probiotics, saliva stimulants — no guideline was possible because the evidence was insufficient ^[1];
• separately, chewing gum was found NOT to be effective for the prevention of oral mucositis in paediatric patients with haematological or solid cancers treated with chemotherapy ^[1].

WHAT THE QUANTITATIVE REVIEWS SHOW

• a network meta-analysis of 36 randomised trials compared 13 mouthwashes in use in different countries and ranked them by SUCRA; from best downwards: aloe vera juice, Chinese herbal medicine, Bing Peng San, HONEY, Lactobacillus, chamomile, riboflavin, rehabilitation solution, benzydamine, turmeric, aluminium sulfide, povidone-iodine, chlorhexidine — honey came fourth ^[2];
• the authors of that meta-analysis state plainly that the conclusion still needs to be verified by randomised trials with larger samples ^[2];
• an umbrella review of eight systematic reviews covering 257 primary studies identified honey among the agents showing consistent improvement in quality of life across pain relief, oral function and emotional well-being ^[3].

HOW TO READ THIS HONESTLY

The strength of this recommendation is moderate and worth knowing before buying anything. A "Suggestion" on the MASCC/ISOO scale means the evidence points in a direction but is not strong enough to constitute a Recommendation. A SUCRA ranking orders interventions relative to one another and does NOT say by how much honey reduces risk — the meta-analysis abstract reports no effect size and no confidence intervals ^[2]. Note also that the guideline concerns PREVENTION, that is use from the start of treatment, not the relief of mucositis that has already developed.

WHAT IS NOT KNOWN

• no single dose or schedule has been established: the guideline speaks of topical combined with systemic delivery, without specifying the type of honey ^[1]; trials use various honeys, manuka among them, and none has been shown to be superior;
• the evidence concerns primarily head and neck cancer treated with radiotherapy; extending it to other diagnoses and other treatments is unsupported;
• in children, a review of nutritional interventions describes honey-based results as promising but without pooled data ^[5].

SAFETY POINTS TO KEEP IN MIND

• honey is high in sugars, and irradiation of the head and neck region leads to a dry mouth and radiation caries ^[4] — which is why the decision to use it, and the accompanying dental care, is taken together with the treating team and a dentist, not alone;
• honey is not a sterile product; in a patient with profound neutropenia everything taken by mouth is decided by the treating team;
• in people with diabetes, regular honey intake affects glycaemic control and needs to be discussed with the treating physician.

WHAT THIS ENTRY DOES NOT SAY

It is not a recommendation for any individual, it gives no dose or route, and it replaces neither dental prophylaxis nor pain management. It describes only where the evidence stands: there is a positive guideline suggestion of moderate strength, concerning prevention, in one specific diagnosis and one specific treatment modality.

Sources

1. [1] Yarom N i wsp. — Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines, part 2: honey, herbal compounds, saliva stimulants, probiotics and miscellaneous agents, Support Care Cancer 2020 (78 prac zidentyfikowanych, 49 wlaczonych; nowa Sugestia za miodem w profilaktyce OM w raku glowy i szyi; PMID 32056010): europepmc.org ↗
2. [2] The effect of different mouthwashes to prevent oral mucositis in patients with radiotherapy and chemotherapy: a network meta-analysis, BMC Complement Med Ther 2025 (36 badan randomizowanych, 13 plukanek, ranking SUCRA — miod na 4. miejscu; PMID 40611101): europepmc.org ↗
3. [3] Therapeutic Interventions to Manage Oral Mucositis and Their Impact on Quality of Life in Cancer Patients: An Umbrella Review, Pain Res Manag 2026 (8 przegladow systematycznych, 257 badan pierwotnych; PMID 41647299): europepmc.org ↗
4. [4] Radiation-induced oral side effects in head and neck cancer: a scoping review and interdisciplinary recommendations, BMC Oral Health 2026 (151 badan; prochnica, suchosc, martwica popromienna kosci; PMID 41862928): europepmc.org ↗
5. [5] Nutritional and Supplemental Interventions for Prevention and Treatment of Oral Mucositis in Pediatric Oncology, Nutrients 2025 (PMID 41305573): europepmc.org ↗

WHERE THE DEFICIT COMES FROM IN ONCOLOGY

Unlike most nutritional deficits, this one is usually not about what the patient eats. Mechanistic reviews describe it as drug-induced renal magnesium wasting, listing antineoplastic agents, diuretics, some antibiotics and proton pump inhibitors ^[3][4]. The practical consequence is that neither diet nor a tablet can close the tap through which magnesium escapes; losses can only be replaced for as long as their cause persists.

HOW OFTEN IT HAPPENS

In a multicentre study of 304 patients with RAS/RAF wild-type colorectal cancer treated with cetuximab, hypomagnesaemia was found in 29.9% and hypokalaemia in 20.7% ^[1]. A twenty-year pharmacovigilance analysis indicates that of the two anti-EGFR antibodies, panitumumab shows the stronger association with hypomagnesaemia ^[6]. With platinum agents the phenomenon has long been recognised; a case of profound hypomagnesaemia emerging a year after carboplatin has also been described, although this is a single case report, the weakest form of evidence ^[5].

WHAT HAS NOT BEEN CONFIRMED

A belief circulates online that low magnesium signals that the disease is progressing, or conversely that it heralds a good response to treatment. The study cited above tested this directly and found no significant association between hypomagnesaemia and either progression-free or overall survival ^[1]. The negative result is informative in its own right: the disturbance is treated because it has consequences of its own, not because it forecasts anything.

WHY THIS IS NOT A DECISION TO TAKE ALONE: In oncology magnesium is at times part of hospital treatment rather than a pharmacy purchase. In a prospective study of 207 patients with locally advanced head and neck cancer receiving high-dose cisplatin, intravenous magnesium was used as nephroprotection; acute kidney disease occurred in 5.3% of patients (11/207; 95% CI 2.7-9.3) ^[2]. Management reviews additionally list agents that reduce renal magnesium loss, such as amiloride and SGLT2 inhibitors ^[4]. Every one of these decisions — whether, when, in what form and under what laboratory monitoring — belongs to the physician directing the cancer treatment. This service does not interpret laboratory results and does not give doses.

INTERACTIONS AND CAUTIONS

• Proton pump inhibitors, very frequently taken during cancer treatment, lower magnesium in their own right and add to the effect of chemotherapy ^[3][4].
• The deficit may appear with delay, including after platinum treatment has ended, so previous chemotherapy is worth mentioning to any physician, including those outside oncology ^[5].
• Taking magnesium unsupervised may mask a problem whose origin lies in the kidneys and delay its recognition.

WHAT MAGNESIUM DOES NOT DO

None of the sources cited here shows that magnesium supplementation reduces the risk of developing cancer, slows its growth, or increases the effectiveness of anticancer treatment. The role described here concerns a complication of treatment, not the disease itself.

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 IT MATTERS

Hormonal therapy lowers the sex hormones that protect bone. In men on androgen deprivation therapy (ADT), bone mineral density falls by an average of 5–8% during the first year and fracture risk doubles; with long-term ADT, fracture incidence is 20–30% higher than in men not on hormonal therapy ^[1]. In postmenopausal women, aromatase inhibitors and GnRH analogues increase bone turnover and reduce bone density ^[1][2].

WHAT GUIDELINES RECOMMEND

The SEOM–SEIOMM consensus (2026) states a calcium intake of 1000–1200 mg/day and vitamin D supplementation of 800–1000 IU/day for patients at risk of osteoporosis, with higher doses if dietary intake is insufficient ^[1]. The 2025 joint position statement of the bone societies (IOF, ECTS, ESCEO and others) specifies vitamin D3 800–2000 IU/day for women on an aromatase inhibitor, plus 1000 mg calcium daily if dietary calcium is low ^[2].

WHAT SUPPLEMENTATION DOES NOT COVER

Calcium and vitamin D are one component of care, not the whole of it. Once bone density falls below guideline thresholds (T-score below −2.0 on an aromatase inhibitor; more generally T-score ≤ −2.5 or a prior fragility fracture), or when additional risk factors coexist, guidelines call for antiresorptive treatment with bisphosphonates or denosumab ^[1][2]. Decisions about bone density assessment and treatment belong to the treating physician.

INTERACTIONS WITH CANCER TREATMENT

• With bisphosphonates and denosumab, adequate calcium and vitamin D are mandatory rather than optional: these drugs lower blood calcium and can cause hypocalcaemia if intake is inadequate. Registration trials of these agents typically included at least 500 mg calcium and 400 IU vitamin D per day ^[1].
• Before starting antiresorptive treatment, guidelines recommend measuring calcium, vitamin D and renal function ^[1].
• Doses higher than those above have no documented advantage in this setting; high-dose supplementation "just in case" is not the same as correcting a deficiency.

STRENGTH OF EVIDENCE

Moderate. Recommendations on calcium and vitamin D here rest on consistent society position statements and on the known mechanism of bone loss, not on randomised trials showing that supplementation alone reduces fractures in patients on hormonal therapy. The stronger evidence concerns antiresorptive drugs. The honest conclusion: calcium and vitamin D are the foundation on which the rest of management is built, but on their own they do not protect bone against the effects of hormonal therapy.

Sources

1. Beato-Zambrano C i wsp. Bone health in patients with cancer: a SEOM-SEIOMM consensus review. Clin Transl Oncol. 2026;28(8):3059-3074 (PMID 41703396): europepmc.org ↗
2. Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer — updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS and SIOG. J Bone Oncol. 2025;53:100694 (PMID 40726588): europepmc.org ↗
3. Coleman R i wsp. Bone health in cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2020 (PMID 32801018): esmo.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 ↗

WHAT IT IS AND WHY IT IS DISCUSSED

L-carnitine is an amino-acid derivative whose role in the cell is to transport long-chain fatty acids across the inner mitochondrial membrane, enabling their beta-oxidation ^[1]. Because this is part of how the cell produces energy, carnitine is marketed for fatigue — including fatigue during cancer treatment — and also for heart disease, diabetic nerve pain, insulin resistance and male infertility ^[1]. The mechanism sounds persuasive; what follows is what human studies actually showed.

WHAT THE EVIDENCE SAYS

The evidence is inconsistent and its balance is negative.

• Current guidelines do NOT recommend L-carnitine for cancer-related fatigue ^[1].
• In a randomised, double-blind, placebo-controlled phase 3 ECOG trial, four weeks of L-carnitine at 2 g per day did not improve fatigue in patients with invasive malignancies and good performance status ^[2].
• A systematic review with meta-analysis concludes that carnitine supplementation is unlikely to give a clinically meaningful benefit for cancer-related fatigue in the chemotherapy-treated population ^[3].
• Individual small oncology studies described improved nutritional status in pancreatic cancer and reduced muscle spasms caused by vismodegib ^[1]. These are observations from small studies, on endpoints other than fatigue, and they do not offset the phase 3 result.

WARNING: THE DERIVATIVE ACETYL-L-CARNITINE AND NEUROPATHY. This is the most important practical item on this card, and it concerns not L-carnitine itself but its derivative. Acetyl-L-carnitine, studied to PREVENT chemotherapy-induced peripheral neuropathy, in fact INCREASED it, and guidelines do not recommend it for that purpose ^[1]. A supplement whose name sounds like nerve support can therefore worsen the very complication it was meant to prevent.

INTERACTIONS WITH TREATMENT, AND ADVERSE EFFECTS.

• Warfarin: L-carnitine may have additive anticoagulant effects with warfarin, increasing bleeding risk ^[1]. This matters often in oncology, because anticoagulation is standard care for cancer-associated thromboembolism.
• Neurotoxic chemotherapy (platinum agents, taxanes): acetyl-L-carnitine is not to be added for nerve protection — see the warning above ^[1].
• Adverse effects: dyspepsia and heartburn; also reported are flu-like syndrome, injection-site reaction, pain, pharyngitis, headache, diarrhoea and hypertension; high doses may cause an unpleasant body odour ^[1].

WHAT THIS CARD DOES NOT SAY

This is neither a recommendation nor a warning-off for any individual. Fatigue in cancer has many reversible causes — anaemia, hypothyroidism, pain, disturbed sleep, drug effects, malnutrition — and it is identifying those, not a supplement, that changes a patient's situation. Decisions about supplements taken during treatment belong to the treating physician, who knows the patient's full medication list.

Sources

1. [1] Memorial Sloan Kettering Cancer Center, About Herbs — Carnitine (mechanizm, deklarowane zastosowania, podsumowanie kliniczne, brak zalecenia w wytycznych, nasilenie neuropatii przez acetylo-L-karnitynę, interakcja z warfaryną, działania niepożądane): mskcc.org ↗
2. [2] Cruciani RA i wsp. L-carnitine supplementation for the management of fatigue in patients with cancer: an Eastern Cooperative Oncology Group phase III, randomized, double-blind, placebo-controlled trial. PMID 22987089: pubmed.ncbi.nlm.nih.gov ↗
3. [3] Efficacy and effectiveness of carnitine supplementation for cancer-related fatigue: a systematic literature review and meta-analysis (PMC5707696): pmc.ncbi.nlm.nih.gov ↗

WHAT IT IS AND WHY PATIENTS TAKE IT

Ashwagandha (Withania somnifera) is an Ayurvedic herb sold over the counter as a dietary supplement. Cancer patients most often take it on their own hoping to reduce anxiety, stress and fatigue, improve sleep and — less commonly — ease joint pain.

WHAT THE EVIDENCE SHOWS

Clinical data are limited and come from few, small studies. Memorial Sloan Kettering notes reports of reduced chemotherapy-induced fatigue in breast cancer patients, and of improved sleep quality and reduced anxiety. This is not a basis for a recommendation: there are no large randomised trials, no independent confirmation, and the endpoints are subjective.

WHAT ASHWAGANDHA DOES NOT DO

Laboratory studies have shown slowed growth of cancer cells, but — as MSKCC states explicitly — this effect has not been observed in humans. Ashwagandha is not anticancer treatment and does not replace any therapy.

SAFETY — THIS IS THE MAIN ISSUE. Commonly reported adverse effects are drowsiness, nausea, headache, stomach upset and diarrhoea. Serious events have also been reported:

• liver injury associated with use of ashwagandha supplements,
• thyrotoxicosis,
• kidney transplant rejection.

SPECIFIC WARNINGS

• Pregnancy: do not use — the herb may increase the risk of miscarriage.
• Hormone-sensitive prostate cancer: discuss with the treating physician, because ashwagandha may raise testosterone levels.
• Autoimmune disease: the herb may trigger or exacerbate it.
• Liver disease or abnormal liver tests: discuss with the treating physician before considering use.

INTERACTIONS WITH CANCER TREATMENT

• CYP3A4: ashwagandha is a moderate inducer of this enzyme. Many oncology drugs (including kinase inhibitors) are metabolised by it, and induction may lower their blood levels.
• CYP2B6: inhibition shown in vitro.
• Sedatives and antiepileptics (benzodiazepines, barbiturates): ashwagandha has sedative, GABAergic properties; additive effects are possible.
• Thyroid medication: thyroxine levels may rise.
• Digoxin: may cause falsely elevated immunoassay results.

MSKCC notes that the clinical relevance of several of these interactions is yet to be determined — which means they have not been measured, not that they are unimportant.

BOTTOM LINE

The quality of evidence for benefit is limited, while the list of documented hazards — including liver injury and CYP3A4 induction — is concrete. Any supplement use during cancer treatment is a decision for the treating physician, who knows the patient's full medication list.

WHAT IT IS AND WHY PATIENTS TAKE IT

Berberine is an alkaloid found in several medicinal plants (including barberry and goldenseal). It is sold as a dietary supplement. Patients most often take it for reasons unrelated to cancer: type 2 diabetes, raised cholesterol, digestive complaints, and under the banner of "cleansing".

WHAT THE EVIDENCE SHOWS

Memorial Sloan Kettering summarises that several studies and meta-analyses suggest benefit from berberine, but better-designed studies are needed and the effect may be small. Diabetes studies are described as of limited quality. In hyperlipidaemia, improvement in the lipid profile has been reported in people who cannot or will not take statins.

THE ONE ONCOLOGY FINDING

A reduced rate of recurrence of colorectal adenomas has been reported in people after adenoma removal. This is prevention of recurrence of BENIGN lesions with malignant potential, not treatment of colorectal cancer — and it should be read that way. There are no data showing that berberine treats any malignancy.

ADVERSE EFFECTS

Reported as mild: appetite loss, upset stomach, diarrhoea, constipation, rash.

SPECIFIC WARNINGS

• Pregnancy and breastfeeding: do not use — berberine may worsen neonatal jaundice.
• Bosutinib: do not use together (see interactions).
• Immunosuppressants (tacrolimus, ciclosporin): avoid.

INTERACTIONS WITH CANCER AND SUPPORTIVE TREATMENT

• CYP2D6, CYP2C9, CYP3A4: berberine reduces the activity of these enzymes, which can alter levels of many drugs cleared by them — in oncology this includes kinase inhibitors.
• Bosutinib: simulations predict a 1.3-fold increase in drug exposure; MSKCC advises against combining them.
• Tacrolimus and ciclosporin: berberine raises their blood levels — relevant after transplantation and in graft-versus-host disease.
• Sulfonylureas: additive blood-glucose-lowering effect is possible.

BOTTOM LINE

Berberine is not anticancer therapy and there is no basis for treating it as an adjunct to cancer treatment. It does, however, have a concrete documented interaction profile that can change the levels of drugs a patient is already taking. Any supplement use during cancer treatment is a decision for the treating physician, who knows the patient's full medication list.

WHY PATIENTS REACH FOR IT

Ginkgo biloba is marketed to improve circulation, enhance memory and treat tinnitus ^[1]. In oncology it is taken mainly by people left with problems of concentration, memory and mental speed after chemotherapy — a real and burdensome complaint for which no treatment of proven efficacy exists. That gap is what drives sales of the supplement.

WHAT THE TRIALS SHOWED

Memorial Sloan Kettering Cancer Center summarises the evidence without ambiguity: ginkgo was INEFFECTIVE in preventing chemotherapy-associated cognitive dysfunction in breast cancer patients ^[1]. Large randomised trials, notably the Ginkgo Evaluation of Memory (GEM) study, generally show that supplementation does not improve cognitive performance or prevent Alzheimer's disease or dementia ^[1]. Cancer incidence data from GEM do not support using ginkgo to reduce cancer risk ^[1].

ADVERSE EFFECTS — WHERE THE MAIN RISK LIES. Spontaneous bleeding has been documented, including haematomas and brain haemorrhages ^[1]. Also reported: low blood sodium, seizures in susceptible individuals, and acute haemolytic anaemia in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency ^[1]. In oncology this list carries more weight than in the general population: chemotherapy-induced thrombocytopenia, surgery and biopsies are settings in which a prolonged bleeding time stops being theoretical.

INTERACTIONS WITH CANCER TREATMENT

• Anticoagulants and antiplatelet drugs: ginkgo may induce or prolong bleeding time, creating a serious haemorrhage risk when combined with warfarin or similar agents ^[1].
• CYP450 enzymes: ginkgo both inhibits and induces multiple pathways (CYP3A4, CYP2D6, CYP2B6), potentially altering drug metabolism ^[1]. A large share of anticancer drugs, including kinase inhibitors, is metabolised through CYP3A4, and shifting their concentration in either direction is undesirable.
• Drugs that lower the seizure threshold: combined use increases seizure risk ^[1].
• Reduced effectiveness of efavirenz, midazolam and insulin has also been reported ^[1].

CONTRAINDICATIONS. Avoid during pregnancy, especially near childbirth, because of antiplatelet properties that prolong bleeding time ^[1].

STRENGTH OF EVIDENCE

Moderate — and pointing towards absence of benefit. This grade reflects the fact that the conclusions of ineffectiveness come from randomised trials, including the large GEM study, rather than from observation ^[1]. The harm evidence is of a different kind: it rests on case reports and interaction data, so it does not allow the frequency of complications to be estimated — but it does establish that they are possible and serious.

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 before surgery, during chemotherapy or while on anticoagulation belongs to the treating physician, who knows the full list of medicines taken.

SOURCES.

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

Sources

1. [1] Memorial Sloan Kettering Cancer Center — About Herbs: Ginkgo: 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 ↗

WHERE THE IDEA CAME FROM

Pomegranate (Punica granatum) is a rich source of polyphenols, and laboratory work showed effects on prostate cancer cell proliferation and apoptosis. In 2006 the first clinical trial in men with rising PSA after prostatectomy or radiotherapy was published: a phase II study with no control group, in which mean PSA doubling time increased from 15 months to 54 months ^[1]. The authors stated explicitly that the result warranted testing in a placebo-controlled study ^[1] — yet it is precisely the "15 to 54 months" figure that still circulates today.

WHAT THE CONTROLLED TRIAL SHOWED

A multi-institutional, double-blind, placebo-controlled study enrolled 183 men with rising PSA after primary therapy, randomly assigned 2:1 (extract 102, placebo 64, juice 17) ^[2]. The primary endpoint was change in PSA doubling time. The authors' conclusion is unambiguous: compared with placebo, pomegranate extract did NOT significantly prolong PSA doubling time ^[2].

WHY THE EARLIER RESULT WAS MISLEADING

In the placebo-controlled study, PSA doubling time lengthened significantly in BOTH arms — in the placebo group the median rose from 11.1 months at baseline to 15.6 months ^[2]. This shows that a lengthening of PSA doubling time during follow-up does not by itself demonstrate that a preparation works. The 2006 phase II study had no control group and so could not tell the two apart. It is a textbook illustration of why an uncontrolled result is not enough.

A GENETIC SUBGROUP — WHAT MUST NOT BE READ INTO IT: In an exploratory analysis, men with the manganese superoxide dismutase (MnSOD) AA genotype taking the extract had a change in median PSA doubling time from 13.6 to 25.6 months ^[2]. The authors themselves note that this observation requires prospective hypothesis testing and validation ^[2]. A subgroup identified after the fact is not a basis for using the preparation.

INTERACTIONS WITH CANCER TREATMENT

• CYP3A: in rat studies pomegranate juice inhibited CYP3A activity similarly to grapefruit juice, but human clinical trials did NOT show clinically relevant inhibition ^[3]. Equating pomegranate with grapefruit is therefore unwarranted.
• CYP2C9: inhibition was shown in rats (increased tolbutamide bioavailability); in humans no effect on CYP2C9 activity was found ^[3].
• warfarin: a case report suggests that pomegranate juice may interact with warfarin ^[3].
• metformin: in a rat model, prior administration of the juice reduced metformin efficacy; clinical relevance remains undetermined ^[3].

TOLERABILITY: Pomegranate is generally well tolerated; daily consumption of about 240 ml of juice for over two years produced no significant adverse effects ^[3]. Mild effects reported included nausea, constipation and decreased appetite, with diarrhoea at higher doses in some patients ^[3].

WHAT FOLLOWS

Pomegranate as a fruit and juice is a dietary component with a good safety profile. There is, however, no controlled-trial evidence that pomegranate extract slows the rise of PSA after treatment for prostate cancer. Decisions about management of a rising PSA are made by the treating physician; a supplement replaces neither surveillance nor treatment.

Sources

1. [1] Pantuck AJ i wsp., Phase II study of pomegranate juice for men with rising PSA following surgery or radiation for prostate cancer, Clin Cancer Res 2006: pubmed.ncbi.nlm.nih.gov ↗
2. [2] Pantuck AJ i wsp., A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer, Prostate Cancer Prostatic Dis 2015;18(3):242-8: pubmed.ncbi.nlm.nih.gov ↗
3. [3] Memorial Sloan Kettering Cancer Center, About Herbs: Pomegranate (interakcje i tolerancja): mskcc.org ↗

WHY PATIENTS REACH FOR ALOE

Aloe gel is among the most common home remedies applied to the skin during radiotherapy — it is cheap, available without prescription and associated with soothing burns. Radiation dermatitis affects a large proportion of irradiated patients, and the expectation that a "burn" preparation will help here too is intuitive. Clinical evidence does not clearly bear that intuition out.

WHAT THE BREAST CANCER TRIAL SHOWED

A three-arm randomised phase III trial enrolled 248 patients with breast cancer assigned to powder, aloe cream or placebo cream; acute skin toxicity was scored weekly on a modified 10-point Catterall scale and patients rated their own symptom severity ^[1]. The aloe formulation did NOT reduce acute skin toxicity or symptom severity ^[1]. The authors found no evidence supporting prophylactic use of aloe and stated that their results support a dry powder skin care regimen ^[1]. They also noted that both study creams were associated with a greater skin reaction than the dry powder regimen ^[1].

WHAT THE HEAD AND NECK TRIAL SHOWED

A multicentre, randomised, double-blind, placebo-controlled trial enrolled 120 patients with head and neck cancer receiving concurrent chemoradiation; skin reaction was assessed with the RISRAS scale ^[2]. In the main comparison, median RISRAS values from week 1 to week 8 did NOT differ significantly between groups ^[2]. Differences appeared in individual weeks: moderate to severe erythema occurred in week 5 in 13.6% of patients using aloe versus 27.8% on placebo (p=0.05), and in week 6 in 24.1% versus 42.6% (p=0.038) ^[2].

HOW TO READ THE TWO TOGETHER

The two randomised trials give an inconsistent picture, and in both the main comparison showed no significant difference. A favourable result in individual weeks of follow-up is weaker ground than a result in the planned comparison across the treatment period. The honest conclusion is therefore: there is no high-quality evidence that aloe gel prevents radiation dermatitis or reduces its severity. This is not evidence that the gel is harmful on the skin — it is an absence of confirmed benefit.

ORAL MUCOSITIS

Preliminary findings suggest a benefit of aloe in preventing chemotherapy-induced oral mucositis in adults, and studies in children report a similar benefit ^[3]. These are preliminary data, not established practice.

THE KEY WARNING — GEL IS NOT JUICE: Aloe gel must not be confused with aloe juice or aloe latex; both contain anthraquinone, a cathartic laxative ^[3]. Internal use of aloe should be discouraged because of possible adverse effects ^[3]. Reported effects include stomach pain, nausea, vomiting, seizures, low potassium and liver dysfunction ^[3]. Low potassium matters particularly in cancer patients, who often receive drugs affecting electrolyte balance.

INTERACTIONS WITH CANCER TREATMENT

• liver enzymes: aloe juice inhibited CYP3A4 and CYP2D6, which may affect intracellular concentrations of drugs metabolised by these enzymes ^[3] — this concerns many anticancer drugs;
• surgery: excessive intraoperative bleeding was reported in a patient taking oral aloe vera tablets, under sevoflurane anaesthesia ^[3];
• practical conclusion: information about taking aloe orally should reach the treating team before a planned procedure and when systemic treatment is being decided. The decision rests with the treating physician.

Sources

1. [1] Hoopfer D i wsp., Three-Arm Randomized Phase III Trial: Quality Aloe and Placebo Cream Versus Powder as Skin Treatment During Breast Cancer Radiation Therapy, Clin Breast Cancer 2015: pubmed.ncbi.nlm.nih.gov ↗
2. [2] Reduction in severity of radiation-induced dermatitis in head and neck cancer patients treated with topical aloe vera gel: a randomized multicenter double-blind placebo-controlled trial, Eur J Oncol Nurs 2022: pubmed.ncbi.nlm.nih.gov ↗
3. [3] Memorial Sloan Kettering Cancer Center, About Herbs: Aloe Vera (zapalenie blony sluzowej, ostrzezenia, interakcje): mskcc.org ↗

WHAT IT IS

EGCG (epigallocatechin gallate) is the principal polyphenol of green tea. Two things that are often conflated must be kept apart: an infusion of green tea leaves, and a supplement containing an extract in which the EGCG dose is many times higher. The safety concerns described below apply to extracts, not to tea drunk in ordinary amounts ^[4].

THE MOST IMPORTANT WARNING — BORTEZOMIB (MULTIPLE MYELOMA). Bortezomib carries a boronic acid group. EGCG forms a stable chemical adduct with it, so the drug no longer binds the proteasome — that is, it stops doing what it is given for. In myeloma and glioma cell lines the antitumour effect of bortezomib was blocked, and in a mouse model it was abolished completely ^[2]. The NCI PDQ database describes this mechanism explicitly and notes that human studies have not been performed ^[3]. Memorial Sloan Kettering lists the interaction among its patient warnings ^[4].

• Level of evidence: laboratory and animal studies plus a defined chemical mechanism — there are no clinical data.
• Why it is nevertheless taken seriously: the mechanism is direct and requires no assumption beyond the chemistry of the two molecules.

OTHER DOCUMENTED INTERACTIONS

• Irinotecan — in models, higher plasma drug levels and reduced biliary excretion of the active metabolite SN-38, meaning a risk of increased toxicity ^[4].
• Kinase inhibitors (erlotinib, lapatinib, sunitinib, palbociclib) — reduced oral bioavailability in animal models; a single human case has been reported with sunitinib ^[4].
• Statins — increased exposure to atorvastatin and a marked decrease in exposure to rosuvastatin ^[4].
• Nadolol — the extract inhibits the OATP1A2 transporter and reduces drug absorption ^[4].

WHAT HUMAN STUDIES HAVE NOT SHOWN

• Prostate cancer: a double-blind randomised trial in 97 men with precancerous lesions (HGPIN/ASAP), 400 mg EGCG daily for one year. Cancer was diagnosed in 5 of 49 men on the preparation and 9 of 48 on placebo; p=0.25. The primary endpoint was not met ^[1].
• Oral precancerous lesions: a randomised phase 2 trial showed a clinical response in 50% (n=28) versus 18.2% on placebo (n=11), p=0.09 — not statistically significant ^[6].
• Chronic lymphocytic leukaemia: a single-arm phase 2 study (n=42) reported a response in 69% of patients, but measured by a surrogate marker (fall in lymphocyte count, reduction of nodal masses), not by survival or time to treatment ^[7].
• Neither the NCI nor Memorial Sloan Kettering recommends green tea or EGCG for cancer prevention or treatment; the FDA has approved no such indication ^[8].

SAFETY OF EXTRACTS

The European Food Safety Authority concluded that catechins from a traditional infusion are generally safe, whereas doses from supplements of 800 mg EGCG per day and above produced a statistically significant rise in transaminase activity; the panel was unable to identify a safe dose for extracts ^[5]. The NIH LiverTox registry assigns green tea extracts its highest likelihood category for liver injury, describing more than a hundred cases including acute liver failure requiring transplantation; the injury is idiosyncratic and typically appears after one to six months of use ^[9].

WHAT TO DISCUSS WITH THE TREATING PHYSICIAN

Every supplement being taken — and particularly so during treatment with bortezomib, irinotecan or a kinase inhibitor. The decision to stop or continue a preparation rests with the specialist who knows the patient's full medication list; this page describes the state of knowledge, not a recommendation for any individual.

Sources

1. [1] Kumar NB i wsp. Randomized, placebo-controlled trial of green tea catechins for prostate cancer prevention. Cancer Prev Res 2015: pmc.ncbi.nlm.nih.gov ↗
2. [2] Golden EB i wsp. Green tea polyphenols block the anticancer effects of bortezomib. Blood 2009;113(23):5927-37: pubmed.ncbi.nlm.nih.gov ↗
3. [3] NCI PDQ — Cancer Therapy Interactions With Foods and Dietary Supplements (Health Professional Version): cancer.gov ↗
4. [4] Memorial Sloan Kettering Cancer Center — About Herbs: Green Tea: mskcc.org ↗
5. [5] EFSA — Scientific opinion on the safety of green tea catechins (2018): efsa.europa.eu ↗
6. [6] Tsao AS i wsp. Phase II randomized trial of green tea extract in oral premalignant lesions. Cancer Prev Res 2009: pubmed.ncbi.nlm.nih.gov ↗
7. [7] Shanafelt TD i wsp. Phase 2 trial of daily oral Polyphenon E in patients with CLL. Cancer 2013: pubmed.ncbi.nlm.nih.gov ↗
8. [8] NCI PDQ — Prostate Cancer, Nutrition, and Dietary Supplements (Patient Version): cancer.gov ↗
9. [9] NIH LiverTox — Green Tea (Camellia sinensis): ncbi.nlm.nih.gov ↗

WHAT IS BEING STUDIED

Zinc is a trace element required for epithelial healing and normal taste perception. In cancer patients it has been tested in two settings, both linked to radiation of the head and neck region:

• oral mucositis during radiotherapy and chemoradiotherapy,
• radiation-induced taste disturbance (dysgeusia).

WHAT THE EVIDENCE SAYS

The NCI PDQ guidance on oral complications lists “oral zinc supplements in oral cancer patients receiving radiation therapy or chemoradiation”, but assigns it Level of Evidence IV — the lowest rating in that scale, based on expert opinion and observation rather than high-quality trials ^[1].

MSKCC summarises the literature more cautiously and points to a discrepancy that matters in practice: reduced mucositis was reported in some patients receiving radiation or chemotherapy, but NOT in head and neck cancer patients — the very group in which the problem is most common. For taste, results are mixed; a meta-analysis suggests zinc may reduce the INCIDENCE of radiation-induced dysgeusia while having minimal effect on symptoms already present ^[2].

WHO IT APPLIES TO

There is no basis for treating zinc as cancer therapy — none of the referential sources attributes an antitumour effect to it. It is considered only as supportive care for mucosal and taste complications, and the decision to supplement, at what dose and for how long, belongs to the treating physician who knows the patient's other treatment.

ADVERSE EFFECTS AND CAUTIONS

Zinc lozenges cause taste disturbances, nausea, vomiting, upset stomach and diarrhoea. Doses of 100–300 mg per day lead to copper deficiency, depressed immune function, headache, chills, fever and fatigue ^[2] — so the very symptom the supplement is meant to prevent can result from taking too much of it.

INTERACTIONS WITH CANCER TREATMENT

This is the most important part of this entry:

• zinc reduces the availability of fluoroquinolone and tetracycline ANTIBIOTICS; if a physician recommends supplementation, it should be taken 2 hours before or 4 hours after the antibiotic ^[2]. In neutropenic patients, for whom antibiotics can be life-saving, this matters directly;
• the immune suppression seen with chronic zinc excess is particularly unwelcome during myelosuppressive chemotherapy;
• zinc-induced copper deficiency may compound treatment-related anaemia and obscure its cause.

WHAT WE DO NOT KNOW

There is no agreement on dose, timing or duration of supplementation, and it is unclear whether any benefit exists in head and neck cancer at all. “No high-quality evidence” is an honest summary of the current state of knowledge.

Sources

1. NCI PDQ — Oral Complications of Chemotherapy and Head/Neck Radiation (Health Professional Version): cancer.gov ↗
2. Memorial Sloan Kettering Cancer Center — About Herbs: Zinc: mskcc.org ↗

WHAT THE EVIDENCE SHOWS

The strongest evidence is the VITAL trial (NEJM 2019) — randomised, placebo-controlled, two-by-two factorial, 25,871 participants (men aged 50+, women aged 55+), vitamin D3 2000 IU daily ^[1]. The primary endpoint, invasive cancer, did not differ between groups (HR 0.96; 95% CI 0.88-1.06; p=0.47), and neither did site-specific cancers: breast HR 1.02, prostate HR 0.88, colorectal HR 1.09 ^[1]. The NCI summarises the randomised evidence in the same way: vitamin D supplements, with or without calcium, do not reduce the risk of developing cancer overall or of specific cancers ^[2].

STRENGTH OF EVIDENCE

High for the absence of an effect on incidence (a large randomised trial with a hard endpoint). Low for cancer mortality: the HR of 0.83 comes from a secondary endpoint and its confidence interval crosses 1.0, so the result cannot be distinguished from chance ^[1].

WHO IT CONCERNS

Measuring and correcting vitamin D status in a person with cancer is justified by bone health and deficiency, not by cancer treatment — particularly in patients who are immobilised, hospitalised for long periods, have limited sun exposure, or receive drugs affecting calcium metabolism.

CAUTION AND CONTRAINDICATIONS

The NCI gives a safe upper limit of 100 µg per day (4000 IU) for adults and children aged 8+, with recommended intakes of 15 µg (600 IU) up to age 70 and 20 µg (800 IU) above ^[2]. Excess vitamin D causes calcinosis (calcium salt deposits in kidneys, heart or lungs) and hypercalcaemia ^[2]. Doses far above 4000 IU, marketed as "anticancer", have no support in the evidence and carry this risk ^[2]. The NCI also advises against increasing sun exposure to raise vitamin D levels, as this increases skin cancer risk ^[2].

INTERACTIONS WITH CANCER TREATMENT

The cited reference sources describe no direct interaction between vitamin D and anticancer drugs at the level of drug metabolism ^[1][2]. What is clinically relevant is the metabolic consequence of excess: hypercalcaemia ^[2]. In a person with cancer, hypercalcaemia may also be a manifestation of the disease itself (bone metastases, paraneoplastic syndromes), so its occurrence during supplementation calls for medical assessment rather than self-directed dose changes.

Sources

1. Manson JE et al. — Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease, N Engl J Med 2019 (badanie VITAL, PMID 30415629): europepmc.org ↗
2. National Cancer Institute — Vitamin D and Cancer, NCI Fact Sheet 2023: cancer.gov ↗

WHAT THE EVIDENCE SHOWS

The National Cancer Institute lists St John's wort among supplements that must be discussed with the treating team, stating plainly: "St. John's [wort], which some people use for depression, may cause certain cancer drugs to not work as well as they should ^[1]." A review of herb–chemotherapy interactions in Frontiers in Oncology (2019) names St John's wort among six herbal products with interactions demonstrated in humans rather than only in the laboratory, mediated by inhibition or induction of drug-metabolising enzymes ^[2].

HOW IT WORKS

St John's wort induces the CYP3A4 isoenzyme of the cytochrome P450 system and P-glycoprotein — the very pathways by which the body breaks down and clears a large share of anticancer drugs, particularly oral ones ^[2]. The effect is the opposite of what the patient intends: the drug is cleared faster, blood levels fall, and treatment may lose effectiveness even though the full prescribed dose is being taken ^[1][2].

THE SCOPE OF WHAT WE STATE HERE

We deliberately do not quote by how many per cent the levels of specific drugs fall. Publications reporting such figures exist, but we could not confirm them in the reference-class sources available to us — and an unverified number is worse than no number. For a patient's decision the direction of the effect is enough, and it is not disputed: St John's wort WEAKENS the action of some anticancer drugs.

WHO SHOULD PAY PARTICULAR ATTENTION

Anyone on systemic treatment, especially oral targeted agents and oral chemotherapy, and anyone reaching for St John's wort because of low mood during cancer treatment — precisely the situation in which the interaction risk is highest. St John's wort is also an ingredient in herbal blends and calming preparations, so the composition is worth checking, not just the brand name.

WHAT TO DO

Every supplement taken, including herbal and over-the-counter products, should be reported to the treating physician and clinical pharmacist BEFORE treatment starts ^[1]. Antidepressants should never be stopped or replaced with St John's wort on one's own; low mood during cancer is a medical problem with treatment that can be chosen with interactions in mind.

Sources

1. National Cancer Institute — Complementary and Alternative Medicine (CAM), cancer.gov 2024: cancer.gov ↗
2. Fasinu PS, Rapp GK — Herbal Interaction With Chemotherapeutic Drugs — A Focus on Clinically Significant Findings, Frontiers in Oncology 2019 (PMID 31850232): europepmc.org ↗

WHAT THE EVIDENCE SAYS The broadest appraisal is a 2025 systematic review (European Journal of Clinical Pharmacology) covering 34 randomised trials and 2,580 patients undergoing cancer treatment ^[1]. Patients most often had head and neck cancers, followed by breast, prostate and colorectal cancer; curcumin was given topically or systemically ^[1]. Results for oral and skin symptoms, pain, body weight, body composition, survival and disease progression were heterogeneous ^[1]. The authors recorded significant findings only for oral mucositis and weight loss ^[1].

STRENGTH OF EVIDENCE — WEAK The authors state plainly that all included studies had a moderate to high risk of bias, and that because of heterogeneous results and methodological limitations no clear statement about the effectiveness of curcumin in cancer patients can be made ^[1]. Higher-quality research is needed ^[1]. A harm was also recorded: in one trial vomiting was significantly more frequent in the curcumin group ^[1].

INTERACTIONS WITH CANCER TREATMENT This is the most important part of this entry. In a 2019 study (Cancers), in breast cancer patients taking tamoxifen, adding curcumin (1,200 mg three times daily) reduced the area under the curve for endoxifen by 7.7% (95% CI: −15.4 to 0.7%; p=0.07), and curcumin with piperine by 12.4% (95% CI: −21.9 to −1.9%; p=0.02) ^[2]. Endoxifen is the active metabolite of tamoxifen — the form of the drug that does the work ^[2]. The authors conclude that co-treatment with curcumin could lower endoxifen concentrations below the threshold for efficacy, in their estimate potentially in 20–40% of patients, especially in extensive CYP2D6 metabolisers ^[2]. Note that piperine, added to supplements precisely to improve curcumin absorption, made the unfavourable effect LARGER in this study ^[2].

The National Cancer Institute states the general rule: “Tell your doctor if you're taking any dietary supplements, even vitamins, no matter how safe you think they are”, noting that some such products can change how cancer treatment works ^[3].

THE SCOPE OF WHAT WE WRITE HERE We give no figures for interactions between curcumin and cytotoxic drugs or kinase inhibitors, because we could not confirm them in accessible reference-class sources — the only clinically confirmed interaction in patients is the tamoxifen interaction described above. We also found no clinical data on perioperative bleeding risk in cancer patients taking curcumin. A missing number here is information, not an oversight: an unverified number would be worse than none.

This page describes the state of knowledge. It is not advice for any individual and not a recommendation to take or stop any preparation.

Sources

1. Gutsche et al. — Curcumin as a complementary treatment in oncological therapy: a systematic review, European Journal of Clinical Pharmacology 2025: europepmc.org ↗
2. Hussaarts et al. — Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen, Cancers 2019: europepmc.org ↗
3. National Cancer Institute — Complementary and Alternative Medicine (CAM): cancer.gov ↗

WHAT THE EVIDENCE SAYS The strongest available appraisal is a 2022 meta-analysis (Nutrition Research) of 12 controlled trials and 1,184 patients with cancer cachexia ^[1]. The result is split: quality of life improved (standardised mean difference 0.70; 95% CI 0.01–1.40; p=0.048) and survival was longer (median survival ratio 1.10; 95% CI 1.02–1.19; p=0.014), while body weight did not increase (SMD 0.10; 95% CI −0.06 to 0.26; p=0.236) and lean body mass did not change significantly (SMD −0.17; 95% CI −0.36 to 0.03; p=0.095) ^[1]. The authors' conclusion is literal: n-3 PUFAs improved quality of life and survival, but not body weight ^[1].

STRENGTH OF EVIDENCE — MODERATE, RESULTS DIVERGENT The upper confidence bound for quality of life (1.40) and the lower bound for survival (1.02) show these are borderline findings drawn from trials of varying methodology ^[1]. Cancer cachexia cannot be reversed by nutritional measures alone — we write about this separately in the entry on nutrition in cachexia — and omega-3 does not change that picture.

INTERACTIONS AND SAFETY The most common concern is bleeding. A meta-analysis of 11 randomised trials covering 120,643 participants (Journal of the American Heart Association, 2024) found no increase in bleeding events with omega-3 supplementation (rate ratio 1.09; 95% CI 0.91–1.31; p=0.34); haemorrhagic stroke, intracranial bleeding and gastrointestinal bleeding were likewise similar ^[2]. The caveat concerns high-dose purified EPA: in a prespecified analysis the relative risk of bleeding rose by 50%, with only a very modest rise in absolute risk (0.6%) ^[2]. Risk tracked the dose of EPA (risk difference 0.24; 95% CI 0.05–0.43; p=0.02), not the background use of antiplatelet therapy (risk difference −0.01; 95% CI −0.02 to 0; p=0.056) ^[2]. AN IMPORTANT CAVEAT: the abstract of this meta-analysis does not separate out cancer patients, so carrying its result over to people on chemotherapy or before surgery is extrapolation rather than direct data ^[2].

A separate, unsettled question is the use of antioxidant preparations during chemotherapy and radiotherapy — the literature calls the risk–benefit balance in that situation a controversial topic. The National Cancer Institute states the general rule: “Tell your doctor if you're taking any dietary supplements, even vitamins, no matter how safe you think they are” ^[3].

THE SCOPE OF WHAT WE WRITE HERE We give no target doses or dosing schedule, because that would be advice for an individual rather than a description of the state of knowledge. Nor did we find data on patients taking warfarin or direct oral anticoagulants concurrently — the meta-analysis cited examined only antiplatelet background therapy ^[2]. This page is not advice for any individual.

Sources

1. Jin X et al. — Omega-3 polyunsaturated fatty acids improve quality of life and survival, but not body weight in cancer cachexia: a systematic review and meta-analysis of controlled trials, Nutrition Research 2022: europepmc.org ↗
2. Javaid M et al. — Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials, Journal of the American Heart Association 2024: europepmc.org ↗
3. National Cancer Institute — Complementary and Alternative Medicine (CAM): cancer.gov ↗

WHAT THIS ENTRY COVERS

This concerns cancer-related fatigue — exhaustion out of proportion to exertion and not relieved by rest, the most commonly reported symptom during cancer treatment. The entry covers one specific botanical: the root of American ginseng (Panax quinquefolius). It does NOT cover Asian ginseng (Panax ginseng) or Korean red ginseng — different species with a different ginsenoside profile, and the recommendation cited below was formulated for the American species only.

WHAT THE EVIDENCE SHOWS

The principal evidence is a multicentre, double-blind, placebo-controlled randomised trial, NCCTG N07C2 (JNCI, 2013; PMID 23853057): 364 patients from 40 institutions, 2,000 mg of ground root daily for 8 weeks.

• primary endpoint (general subscale of the MFSI-SF) at 8 weeks: change score 20.0 (SD 27) with ginseng versus 10.3 (SD 26.1) with placebo, p = .003
• the difference was NOT significant at 4 weeks — the effect emerged only with longer use

The ASCO/Society for Integrative Oncology guideline on the management of cancer-related fatigue lists American ginseng among options that "may be recommended in adults undergoing cancer treatment", while stating that certainty and quality of evidence for fatigue interventions are low to moderate. This is conditional wording ("may be"), not a strong recommendation.

A smaller, more recent placebo-controlled randomised trial in Supportive Care in Cancer (2026; PMID 41838185) in 65 survivors of gastrointestinal cancer reported improved fatigue scores at 4 weeks (3.99 ± 0.86 vs 5.37 ± 1.27; p < .001), but it used a Panax ginseng extract at 250 mg — a different species and dose from N07C2, so the two results should not be read as confirming one another.

WHAT THESE RESULTS DO NOT SAY

They do not say that ginseng affects the course of the cancer — the endpoint measured was how patients feel, not survival or treatment response. Nor do they make it a first-line measure: in the same guideline the best-documented interventions for fatigue are physical activity and psychological approaches, not oral products. Finally, it is unknown whether the effect persists after stopping, or whether it applies to fatigue that continues long after treatment ends.

INTERACTIONS WITH CANCER TREATMENT — MANDATORY SECTION.

• WARFARIN and other vitamin K antagonists: ginseng has been described as potentially lowering INR, i.e. weakening anticoagulation. In cancer patients, in whom thrombosis is a frequent complication, this matters practically.
• DRUGS METABOLISED BY CYP3A4, including tyrosine kinase inhibitors (e.g. imatinib): liver injury has been reported with concurrent ginseng use. The interaction mechanism is the same as for St John's wort, though its direction and magnitude are less well documented.
• ANTIDIABETIC DRUGS: ginseng may lower blood glucose, so the effect adds to glucose-lowering therapy.
• OESTROGEN-LIKE ACTIVITY: ginsenosides show oestrogenic activity in vitro, and ethanol-extracted preparations contain more of them. N07C2 deliberately used pure ground root rather than an ethanol extract. In hormone-dependent cancers this is a reason for caution, although clinical evidence of harm is lacking.

THE DECISION BELONGS TO THE PHYSICIAN

Cancer-related fatigue has reversible causes that must be excluded first — anaemia, hypothyroidism, pain, sleep disturbance, depression, drug effects. A supplement does not replace that work-up. Introducing any botanical product during chemotherapy, targeted therapy or anticoagulation requires agreement with the treating physician and clinical pharmacist.