Use of High-Dose Melatonin May Decrease Risk for Colorectal Cancers

Colorectal cancer, intestinal carcinoma, bowel neoplasia, 3D illustration showing malignant tumor in intestine
Investigators assessed whether the use of melatonin was associated with a decreased risk for colorectal cancer.

A nation-wide cohort study found that individuals who used melatonin had a lower risk for colorectal cancer (CRC). These findings were published in Clinical and Translational Gastroenterology.

Swedish-born residents (N=9,147,428) who did not have cancer at baseline and were included in the Swedish Total Population Register between 2005 and 2015 were assessed for CRC diagnosis and mortality. Data from the Swedish Prescribed Drug Register were used to determine which individuals were using melatonin during the same time period. Melatonin users aged ³50 years (n=58,657) were matched for age, sex, education, and family history of CRC in a 1:3 ratio with nonusers (n=175,971) to assess trends in CRC.

Users of melatonin tended to have more inflammatory bowel disease, obesity, and chronic obstructive pulmonary disease; they were also found to use more aspirin, metformin, and statins, and more likely to undergo colonoscopy screening, compared with nonusers (all P <.001).

Compared with nonusers, CRC risk was decreased among the melatonin cohort (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.72-0.92; P =.001).

Stratified by cancer site, melatonin was associated with decreased risk for rectal cancer (aHR, 0.73; 95% CI, 0.58-0.93; P =.011) but not proximal colon (P =.237) or distal colon (P =.058) cancers.

Stratified by cancer stage, melatonin was associated with decreased risk for stage I or II cancers (aHR, 0.78; 95% CI, 0.65-0.94; P =.010) and stage III or IV cancers (aHR, 0.82; 95% CI, 0.68-0.99; P =.041).

The protective effect of melatonin was observed among individuals aged 60 to 69 years (aHR, 0.78; 95% CI, 0.63-0.98) and ³70 years (aHR, 0.81; 95% CI, 0.68-0.95), women (aHR, 0.79; 95% CI, 0.68-0.93), and those who used a cumulative dose of ³90 cumulative defined daily doses (aHR, 0.66; 95% CI, 0.50-0.86).

These data may have been biased by the choice to correct for colonoscopy, which could have also included some adjustment for health-related behaviors that differed between individuals who chose to undergo CRC screening.

These data indicated that CRC risk, especially for rectal cancer, may be reduced with use of melatonin. These trends were significant for women, older individuals, and those taking the highest dose of melatonin.


Zhang N, Sundquist J, Sundquist K, Ji J. Use of melatonin is associated with lower risk of colorectal cancer in older adults. Clin Transl Gastroenterol. 2021;12(8):e00396. doi:10.14309/ctg.0000000000000396