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Combined Supplementation with Vitamin B-6 and Curcumin is Superior to Either Agent Alone in Suppressing Obesity-Promoted Colorectal Tumorigenesis in Mice.

Publication ,  Journal Article
Wu, X; Ueland, PM; Roper, J; Koh, GY; Liang, X; Crott, JW; Yilmaz, ÖH; Bronson, RT; Mason, JB
Published in: J Nutr
December 3, 2021

BACKGROUND: Obesity increases the colorectal cancer risk, in part by elevating colonic proinflammatory cytokines. Curcumin (CUR) and supplemental vitamin B-6 each suppress colonic inflammation. OBJECTIVES: We examined whether the combination of CUR and vitamin B-6 amplifies each supplement's effects and thereby suppress obesity-promoted tumorigenesis. METHODS: Male Friend Virus B (FVB) mice (4-week-old; n = 110) received 6 weekly injections of azoxymethane beginning 1 week after arrival. Thereafter, they were randomized to receive a low-fat diet (10% energy from fat), a high-fat diet (HFD; 60% energy from fat), a HFD containing 0.2% CUR, a HFD containing supplemental vitamin B-6 (24 mg pyridoxine HCl/kg), or a HFD containing both CUR and supplemental vitamin B-6 (C + B) for 15 weeks. Colonic inflammation, assessed by fecal calprotectin, and tumor metrics were the primary endpoints. The anti-inflammatory efficacy of the combination was also determined in human colonic organoids. RESULTS: HFD-induced obesity produced a 2.6-fold increase in plasma IL-6 (P < 0.02), a 1.9-fold increase in fecal calprotectin (P < 0.05), and a 2.2-fold increase in tumor multiplicity (P < 0.05). Compared to the HFD group, the C + B combination, but not the individual agents, decreased fecal calprotectin (66%; P < 0.01) and reduced tumor multiplicity and the total tumor burden by 60%-80% (P < 0.03) in an additive fashion. The combination of C + B also significantly downregulated colonic phosphatidylinositol-4,5-bisphosphate 3-kinase, Wnt, and NF-κB signaling by 31%-47% (P < 0.05), effects largely absent with the single agents. Observations that may explain how the 2 agents work additively include a 2.8-fold increased colonic concentration of 3-hydroxyanthranillic acid (P < 0.05) and a 1.3-fold higher colonic concentration of the active coenzymatic form of vitamin B-6 (P < 0.05). In human colonic organoids, micromolar concentrations of CUR, vitamin B-6, and their combination suppressed secreted proinflammatory cytokines by 41%-93% (P < 0.03), demonstrating relevance to humans. CONCLUSIONS: In this mouse model, C + B is superior to either agent alone in preventing obesity-promoted colorectal carcinogenesis. Augmented suppression of procancerous signaling pathways may be the means by which this augmentation occurs.

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Published In

J Nutr

DOI

EISSN

1541-6100

Publication Date

December 3, 2021

Volume

151

Issue

12

Start / End Page

3678 / 3688

Location

United States

Related Subject Headings

  • Vitamins
  • Vitamin B 6
  • Pyridoxine
  • Obesity
  • Nutrition & Dietetics
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Dietary Supplements
  • Diet, High-Fat
 

Citation

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Wu, X., Ueland, P. M., Roper, J., Koh, G. Y., Liang, X., Crott, J. W., … Mason, J. B. (2021). Combined Supplementation with Vitamin B-6 and Curcumin is Superior to Either Agent Alone in Suppressing Obesity-Promoted Colorectal Tumorigenesis in Mice. J Nutr, 151(12), 3678–3688. https://doi.org/10.1093/jn/nxab320
Wu, Xian, Per M. Ueland, Jatin Roper, Gar Yee Koh, Xu Liang, Jimmy W. Crott, Ömer H. Yilmaz, Roderick T. Bronson, and Joel B. Mason. “Combined Supplementation with Vitamin B-6 and Curcumin is Superior to Either Agent Alone in Suppressing Obesity-Promoted Colorectal Tumorigenesis in Mice.J Nutr 151, no. 12 (December 3, 2021): 3678–88. https://doi.org/10.1093/jn/nxab320.
Wu, Xian, et al. “Combined Supplementation with Vitamin B-6 and Curcumin is Superior to Either Agent Alone in Suppressing Obesity-Promoted Colorectal Tumorigenesis in Mice.J Nutr, vol. 151, no. 12, Dec. 2021, pp. 3678–88. Pubmed, doi:10.1093/jn/nxab320.
Wu X, Ueland PM, Roper J, Koh GY, Liang X, Crott JW, Yilmaz ÖH, Bronson RT, Mason JB. Combined Supplementation with Vitamin B-6 and Curcumin is Superior to Either Agent Alone in Suppressing Obesity-Promoted Colorectal Tumorigenesis in Mice. J Nutr. 2021 Dec 3;151(12):3678–3688.
Journal cover image

Published In

J Nutr

DOI

EISSN

1541-6100

Publication Date

December 3, 2021

Volume

151

Issue

12

Start / End Page

3678 / 3688

Location

United States

Related Subject Headings

  • Vitamins
  • Vitamin B 6
  • Pyridoxine
  • Obesity
  • Nutrition & Dietetics
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Dietary Supplements
  • Diet, High-Fat