Magnesium-L-threonate May Reduce Opioid Use, Constipation in Cancer-Related Pain

The oral magnesium compound L-TAMS enhances the analgesic effect of opioids and reduces the opioid dosage in patients with cancer-related pain.

Magnesium-L-threonate (L-TAMS) had a better analgesic effect compared with placebo while reducing opioid dosage and opioid-induced constipation in patients with cancer-related pain, according to study findings from a prospective, randomized, double-blind trial published in Cancer Medicine.

For the analysis, researchers enrolled 83 patients who were receiving oral opioids daily for cancer-related pain. The patients receiving L-TAMS and placebo had a mean [SD] age of 66.17[12.66] and 69.51[11.36] years; 57.1% and 53.7% were men; and 64.3% and 51.2% had a history of radiation or chemotherapy, respectively. In addition, patients had a 24-hour average Visual Analogue Scale (VAS) score (0–10) of at least 4 or breakthrough cancer pain episodes 3 or more times per day.

Patients were randomly assigned 1:1 to receive 1.5 or 2.0g L-TAMS (n=42) or placebo (n=41) taken 30 minutes prior to daily opioid medication for 12 weeks. The primary outcome was the change in oral morphine equivalent daily dose (OMEDD).

More clinical samples and longer follow-up period are necessary to determine the impact of oral L-TAMS on opioid tolerance in cancer patients.

At day 14, patients in the L-TAMS and placebo groups increased their OMEDDs by an average of 5.48 and 10.24 mg per day, which were both significant increases from baseline (both P <.05), but the level of increase did not differ between groups (P =.19).

A day 30, the increase in OMEDDs from baseline was 9.85 mg per day among the L-TAMS recipients, which was significantly lower than the placebo group (mean difference [MD], 20.49 mg/d; P <.05). Similar trends were observed at days 60 (P <.05) and 90 (P <.01).

The L-TAMS recipients reported significantly lower VAS pain scores than the placebo recipients on days 14 (mean, 5.83 vs 6.21 points; P <.05) and 90 (mean, 5.47 vs 5.93 points; P <.05), respectively.

The most common side effects in this trial were constipation, nausea, vomiting, pruritus, dizziness, and urine retention, which occurred at similar rates between cohorts. However, researchers found that on day 7, Wexner constipation scores started to decrease significantly among the L-TAMS recipients while remaining stable among placebo recipients (mean, 15.70 vs 18.12 points; P <.001), respectively. The Wexner scores stabilized in the L-TAMS group on day 21 at 12.81 points, which was significantly lower than the placebo recipients (mean, 17.78; P <.001).

Study limitations included the small sample size, and that patient blood magnesium levels and their changes were not measured. In addition, there was no specified protocol or criteria for opioid dose escalation.

“More clinical samples and longer follow-up period are necessary to determine the impact of oral L-TAMS on opioid tolerance in cancer patients,” the study authors concluded.


Wu S, Jin T, Ma B, et al. Oral application of magnesium-L-threonate enhances analgesia and reduces the dosage of opioids needed in advanced cancer patients—A randomized, double-blind, placebo-controlled trial. Cancer Med. Published January 26, 2023. doi:10.1002/cam4.4922