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 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 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 ↗

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 ↗

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 ↗

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 ↗