Skip to content

Post-Diagnosis Multivitamin Supplementation May Prolong Survival Among Patients With Nonmetastatic CRC

Key findings

  • This study examined relationships between mortality and multivitamin supplementation after diagnosis of colorectal cancer (CRC) in 2,424 participants from the Nurses' Health Study and the Health Professionals Follow-up Study
  • Users of 3–5 multivitamin tablets/week after CRC diagnosis had a lower risk of CRC-specific mortality (HR, 0.55; P=0.005) and lower risk of all-cause mortality (HR, 0.81; P=0.04)
  • Users of 6–9 tablets/week had a lower risk of all-cause mortality (HR, 0.79; P<0.001), but users of ≥10 tablets/week had an increased risk of CRC-specific mortality (HR, 1.60; P=0.02)
  • A dose–response analysis showed the risk of both CRC-specific and all-cause mortality was lowest for users of 3–5 tablets/week
  • In a joint analysis of pre- and post-diagnosis use, patients who initiated use after CRC diagnosis at a modest dose had lower all-cause mortality than never-users; pre-diagnosis users who discontinued use after diagnosis had higher all-cause mortality

Multivitamin components, such as vitamin C, vitamin D, folate, retinol, and selenium, have been shown in preclinical studies to have anti–colorectal cancer (CRC) properties. Furthermore, in recent randomized controlled trials, vitamin C and vitamin D improved the prognosis of patients with advanced CRC.

Mingyang Song, MBBS, ScD, a researcher in the Clinical and Translational Epidemiology Unit and Division of Gastroenterology at Massachusetts General Hospital and associate professor of epidemiology and nutrition at Harvard T.H. Chan School of Public Health, and colleagues conducted the first prospective study of the prognostic influence of multivitamin supplements among patients with non-metastatic CRC.

In Cancer, they report that using multivitamin supplements at a moderate dose after diagnosis was associated with lower CRC-specific and overall mortality. In contrast, a high dose was actually associated with higher CRC-specific mortality.

Methods

The team analyzed data from two large, well-characterized U.S. cohorts:

  • The Nurses' Health Study (NHS), which enrolled 121,701 female registered nurses, ages 30 to 55, in 1976
  • The Health Professionals Follow-up Study (HPFS), which enrolled 51,529 male health professionals, ages 40 to 75, in 1986

Participants completed a questionnaire about their medical history and lifestyle at baseline and every two years after that. The baselines for the current analysis were 1980 for the NHS and 1986 for the HPFS, when detailed data on multivitamin supplementation were first collected.

This analysis included 2,424 participants diagnosed with new-onset stage I–III CRC and provided information about pre- and post-diagnosis multivitamin use. The median follow-up period was 11 years.

Multivitamins and Survival

After CRC diagnosis, compared with non-users:

  • Users of 3–5 tablets/week had a lower risk of CRC-specific mortality (HR, 0.55; P=0.005)
  • Users of 3–5 tablets/week had lower all-cause mortality (HR, 0.81; P=0.04)
  • Users of 6–9 tablets/week had lower all-cause mortality (HR, 0.79; P<0.001)
  • Users of ≥10 tablets/week had an increased CRC-specific mortality (HR, 1.60; P=0.02)

No significant associations were found for users of 1–2 tablets/week.

A dose-response analysis showed the maximum reduction of both CRC-specific and all-cause mortality was at three to five tablets/week. For CRC-specific mortality, users of more than eight tablets/week had an even higher risk of death than non-users.

Pre- vs. Post-Diagnostic Use

In further analysis, the team adjusted for multivitamin use before CRC diagnosis. Compared with non-users in both periods, the risk of all-cause mortality was:

  • Lower in new users of <10 tablets/week after CRC diagnosis (HR, 0.81; P=0.005)
  • Higher in new users of ≥10 tablets/week after diagnosis (HR, 1.58; 95% CI, 1.07–2.33)
  • Higher in participants who discontinued multivitamin use after diagnosis (HR, 1.35; 95% CI, 1.14–1.59)

For CRC-specific mortality, there were no significant associations.

Commentary

Antioxidant vitamins have anti-inflammatory properties and improve endothelial function. In patients with CRC, the systemic alterations associated with the cancer and its treatment may enable a survival-prolonging benefit of post-diagnosis multivitamin supplementation.

Conversely, systemic adaptations to these properties may lead to a withdrawal effect (dysregulation of the immune system) when multivitamin use is discontinued, negatively influencing survival.

Clinical trials are needed in the postoperative setting to assess the influence of multivitamin use at different doses among CRC patients with different stages of disease.

45%
less risk of colorectal cancer–specific mortality among patients with nonmetastatic colorectal cancer who used 3–5 multivitamin tablets/week after diagnosis

19%
less risk of all-cause mortality among patients with nonmetastatic colorectal cancer who used 3–5 multivitamin tablets/week after diagnosis

21%
less risk of all-cause mortality among patients with nonmetastatic colorectal cancer who used 6–9 multivitamin tablets/week after diagnosis

60%
greater risk of colorectal cancer–specific mortality among patients with nonmetastatic colorectal cancer who used ≥10 multivitamin tablets/week after diagnosis

Learn more about the Division of Gastroenterology

Refer a patient to the Division of Gastroenterology

Related topics

Related

Samuel J. Klempner, MD, and colleagues determined adagrasib shows promising clinical activity in pretreated patients with advanced colorectal cancer with a KRAS G12C mutation. The activity appears to be even greater in combination with cetuximab where the objective response rate was 46%.

Related

Shuji Ogino, MD, PhD, Mingyang Song, MBBS, ScD, and colleagues leveraged data from two large, prospective U.S. studies that showed the use of vitamin C after diagnosis of colorectal cancer with KRAS or BRAF mutations was associated with a 26% reduction in the risk of disease-specific mortality.