MULTIPLE MYELOMA: SUPPLEMENTS, CANNABIS, AND TREATMENT INTERACTIONS
MULTIPLE MYELOMA: SUPPLEMENTS, CANNABIS, AND TREATMENT INTERACTIONS
No supplement or cannabis product has demonstrated disease-modifying benefit in multiple myeloma, and NCCN explicitly discourages routine supplement use in cancer survivors except for documented deficiency or comorbid indication, with antioxidants to be avoided during active chemotherapy.
[1]
The evidence-supported roles are narrow:
Repletion of documented vitamin D deficiency as part of bone-health supportive care.
Cannabinoids as a weakly supported option for refractory chemotherapy-induced nausea/vomiting and possibly pain/anxiety.
[2-4]
Several common supplements, including vitamin C and catechol-containing polyphenols such as green tea EGCG, quercetin, myricetin, and curcumin, chemically inactivate boronate proteasome inhibitors such as bortezomib and ixazomib. These supplements should be avoided during those regimens.
[5-8]
Assess vitamin D status in all patients receiving bone-targeting therapy.
Deficiency, defined as less than 20 ng/mL, is common and associated with worse overall survival in myeloma.
General correction:
400 to 2000 IU/day.
Myeloma-specific prospective regimen:
Loading doses of 200,000 IU, given once or twice, plus maintenance dosing of:
• 800 IU/day
• 1600 IU/day
• 3200 IU/day
Maintenance dosing was titrated to the patient’s vitamin D level.
The regimen achieved adequate 25(OH)D levels in 66% of patients.
A reduction in peripheral neuropathy severity was reported in 37% of patients. This finding was exploratory and came from a single-arm study.
Daily dosing, rather than bolus dosing, is associated with reduced cancer mortality in meta-analysis.
Avoid supraphysiologic vitamin D targets because of the risk of hypercalcemia, which is particularly relevant in myeloma.
[2][9-11]
Calcium is reasonable with bisphosphonate or denosumab therapy at National Academy of Medicine intake levels, provided there is no hypercalcemia.
Denosumab carries a risk of hypocalcemia, especially in patients with renal insufficiency.
[2][12-13]
Curcumin is the only supplement with randomized human data in the plasma cell disorder spectrum.
However, the data apply only to MGUS and smoldering myeloma, not active multiple myeloma.
• 4 g/day orally
• An open-label extension using 8 g/day
Curcumin reduced:
• The involved/uninvolved free light chain ratio
• dFLC
• iFLC
• Urinary DPD, a marker of bone resorption
An earlier open-label study using 4 g/day showed a 12% to 30% paraprotein reduction in 5 of 10 patients whose paraprotein was greater than 20 g/L.
No progression-free survival benefit has been shown.
No overall survival benefit has been shown.
The studies were small.
Curcumin is a polyphenol and should not be co-administered with bortezomib or ixazomib.
[5][8][14-15]
The evidence is preclinical only.
EPA and DHA induce apoptosis and enhance bortezomib sensitivity in myeloma cell lines without harming normal peripheral blood mononuclear cells.
A Mendelian randomization analysis suggests a lower incidence risk of multiple myeloma:
OR 0.80.
No treatment dosing has been established.
General cardiovascular doses of approximately 1 g/day are the practical default.
[16-17]
Green tea EGCG has potent preclinical anti-myeloma activity through the 67-kDa laminin receptor.
However, it is clinically contraindicated with boronate proteasome inhibitors because catechins directly inactivate the drug.
[5][8][18-19]
Vitamin B12 and folate deficiencies are common in myeloma and worsen prognosis.
Check for deficiencies and replete when indicated.
[20]
Oral vitamin C at 1 g/day can produce plasma levels that block bortezomib proteasome inhibition and abrogate its antitumor effect in vivo.
Avoid supplemental vitamin C during boronate proteasome inhibitor therapy.
[6]
This category includes catechol or vicinal-diol polyphenols.
These compounds form inactive boronate esters with bortezomib and ixazomib.
Restrict these supplements during proteasome inhibitor treatment.
[5, 7-8]
Examples include:
• Vitamin E
• High-dose multivitamin antioxidants
Antioxidants may blunt the effectiveness of chemotherapy and radiotherapy.
NCCN Survivorship recommends avoiding antioxidants during:
• Chemotherapy
• Radiotherapy
• Photodynamic therapy
[1]
Examples include:
• Alpha-lipoic acid
• Glutathione
• Glutamine
• Acetyl-L-carnitine
There is no prospective trial support for these supplements, and there is possible treatment interference.
At minimum, avoid these supplements on bortezomib dosing days.
[21]
ASCO guidelines recommend against non-evidence-based use.
The guidelines note only weak support for refractory chemotherapy-induced nausea and vomiting when standard antiemetics have failed.
The evidence is weak, conflicting, or negative for:
• Cancer pain
• Appetite and cachexia
• Sleep
• Quality of life
[3][22]
A 2025 meta-analysis included 98 studies.
Pain:
MRAW −1.22.
Anxiety:
MRAW −1.30.
• Fatigue
• Mobility
• Depression
• Overall quality of life
Psychiatric adverse events:
OR 10.62.
Neurologic adverse events:
OR 2.24.
[4]
THC effects are biphasic.
Low and medium doses reduced pain in the nabiximols trial.
High doses did not reduce pain in the trial.
[22]
Dronabinol and nabilone are FDA-approved options for chemotherapy-induced nausea and vomiting.
CBD is FDA-approved only for specific epilepsies.
[23]
Start low and titrate.
Use additional caution in patients with multiple myeloma who are:
• Older
• Frail
• Cytopenic
• Receiving dexamethasone-containing regimens
Cannabinoids studied for possible anti-myeloma activity include:
• CBD
• THC
• CBG
• CBC
• CBN
• Beta-caryophyllene
Reported findings include synergy with carfilzomib and bortezomib.
However, the evidence is entirely preclinical and does not support the therapeutic use of cannabinoids for disease control.
[24-27]
The NCCN Multiple Myeloma supportive care principles frame where vitamin D and bone health fit in the overall treatment algorithm.
MYEL-4. Multiple Myeloma: Primary Treatment and Follow-up/Surveillance for Symptomatic MM. NCCN Guidelines®. Multiple Myeloma, page 12, version 5.2026.
Multiple Myeloma. January 8, 2026.
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To view the most recent and complete version of the guideline, go to NCCN.org.
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