Authored by Dr. Brian Koffman
General Information:
Supplements are not generally recommended unless used to correct a documented deficiency.
Always disclose all supplement use to your hematologist and other doctors.
We know almost half of CLL patients use supplements, but many do not inform their doctors. While most are safe, there is little evidence of benefit, and there is a real risk of drug interactions in some cases.
The biggest issue is that so much remains unknown and underexplored about supplements in CLL. Below is a partial list of some of what we do and don’t know.
Supplements to AVOID During CLL Treatment:
CLL drugs (BTK inhibitors, venetoclax) are metabolized via CYP3A4, making them vulnerable to dangerous interactions:
- St. John’s Wort: reduces drug levels; can render treatment ineffective
- Grapefruit, Seville oranges, starfruit: increase drug toxicity; avoid use together
- Curcumin/turmeric: increases drug exposure ~1.6-fold; strongly consider stopping. Despite there being some preclinical evidence of efficacy, curcumin/turmeric has not been shown in human trials to benefit CLL patients
- Green tea extract (EGCG): modulates CYP3A4; avoid concentrated forms during treatment; EGCG in a high-dose formulation did show activity in small human trials in CLL, but the formulation used is no longer available, and at the doses needed to treat CLL, it can be associated with liver inflammation
- Ginkgo biloba: CYP3A4 inhibitor; strongly consider stopping
- Ginseng: CYP inducer; may reduce drug efficacy
- High-dose antioxidants (vitamin C, E, beta-carotene, selenium): may protect cancer cells from therapy, less of an issue in CLL
Use With Caution:
- Echinacea: modulates CYP3A4; use with caution
- Milk thistle: CYP3A4 inhibition in vitro; caution warranted
- Fish oil / omega-3 — additive bleeding risk with BTK inhibitors; however standard doses (1–2 g/day) generally safe otherwise
Acceptable Supplements:
Recommend testing Vitamin D 25(OH)D blood level at diagnosis: best studied of all supplements; 30–57% of CLL patients are deficient at the time of diagnosis. Supplement to get into the normal range, usually targeting ≥30 ng/mL. Deficiency is associated with shorter time-to-treatment based on real-world data, but there have been no prospective randomized trials that have proven correction improves CLL outcomes.
Daily multivitamin (≤100% Daily Value) acceptable but only needed if dietary intake is inadequate; no cancer-specific benefit. The best source of vitamins and minerals is a balanced diet.
No Proven Benefit in CLL:
Aloe vera, mistletoe, homeopathic remedies, mushroom extracts (reishi, AHCC)
Special Mention:
Cordyceps is a mushroom that may have activity in CLL based on some nicely documented charting of clinical status and lab work by the patients themselves in response to a tea extract made from the fruiting bodies, but its efficacy and safety are yet to be vigorously studied in controlled studies. Research is progressing. At this time, we do not recommend it, and if you are taking it, we urge you to discuss it with your hematologist. See this more detailed discussion of cordyceps.
Referral:
If you are using or considering supplements, please consider a consultation with a well-trained registered dietitian or integrative medicine specialist.
MSK “About Herbs” database is a reliable interaction-checking resource.
