Intest Res.  2022 Jan;20(1):78-89. 10.5217/ir.2020.00124.

Effectiveness of administering zinc acetate hydrate to patients with inflammatory bowel disease and zinc deficiency: a retrospective observational two-center study

Affiliations
  • 1Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
  • 2Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
  • 3Department of Gastroenterology and Hepatology, Sapporo Hokushin Hospital, Sapporo, Japan

Abstract

Background/Aims
Inflammatory bowel disease (IBD) patients frequently have zinc deficiency. IBD patients with zinc deficiency have higher risks of IBD-related hospitalization, complications, and requiring surgery. This study aimed to examine the effectiveness of zinc acetate hydrate (ZAH; Nobelzin) in IBD patients with zinc deficiency.
Methods
IBD patients with zinc deficiency who received ZAH from March 2017 to April 2020 were registered in this two-center, retrospective, observational study. Changes in serum zinc levels and disease activity (Crohn’s Disease Activity Index [CDAI]) before and after ZAH administration were analyzed.
Results
Fifty-one patients with Crohn’s disease (CD, n = 40) or ulcerative colitis (UC, n = 11) were registered. Median serum zinc level and median CDAI scores significantly improved (55.5–91.0 μg/dL, P< 0.001; 171.5–129, P< 0.001, respectively) in CD patients 4 weeks after starting ZAH administration. Similarly, median serum zinc levels and CDAI scores significantly improved (57.0–81.0 μg/dL, P< 0.001; 177–148, P= 0.012, respectively) 20 weeks after starting ZAH administration. Similar investigations were conducted in groups where no treatment change, other than ZAH administration, was implemented; significant improvements were observed in both serum zinc level and CDAI scores. Median serum zinc levels in UC patients 4 weeks after starting ZAH administration significantly improved from 63.0 to 94.0 μg/dL (P= 0.002), but no significant changes in disease activity were observed. One patient experienced side effects of abdominal discomfort and nausea.
Conclusions
ZAH administration is effective in improving zinc deficiency and may contribute to improving disease activity in IBD.

Keyword

Inflammatory bowel diseases; Zinc deficiency; Ulcerative colitis; Crohn disease; Zinc acetate

Figure

  • Fig. 1. Patient enrollment. Of the 56 inflammatory bowel disease (IBD) patients who were administered zinc acetate hydrate (ZAH) for zinc deficiency from March 2017 to April 2020, patients who self-interrupted administration, changed hospitals, or underwent total colectomy for ulcerative colitis (UC) were excluded; a total of 51 patients were included. Of these, analyses were conducted on 32 Crohn’s disease (CD) patients and 9 UC patients whose serum zinc levels were measured 4 weeks after ZAH administration, and 25 CD patients and 5 UC patients whose serum zinc levels were measured 20 weeks after ZAH administration.

  • Fig. 2. Changes in serum zinc levels and Crohn’s Disease Activity Index (CDAI) scores in Crohn’s disease (CD) patients before zinc acetate hydrate (ZAH) administration and 4 weeks or 20 weeks after administration. (A, B) The serum zinc levels of 32 CD patients were measured 4 weeks after ZAH administration. Median serum zinc levels significantly improved from 55.5 μg/dL (31–74) to 91.0 μg/dL (43–171) (P<0.001). Median CDAI scores significantly improved from 171.5 (43–546) to 129 (36–397) (P<0.001). (C, D) There were 25 CD patients whose serum zinc levels were measured 20 weeks after ZAH administration. Median serum zinc levels significantly improved from 57.0 μg/dL (31–73) to 81.0 μg/dL (58–189) (P<0.001). Median CDAI scores significantly improved from 177 (43–546) to 148 (36–397) (P=0.012).

  • Fig. 3. Changes in serum zinc levels and Crohn’s Disease Activity Index (CDAI) scores before and after zinc acetate hydrate (ZAH) administration in Crohn’s disease (CD) patients, in whom changes in treatment other than ZAH were not implemented from 4 weeks before to 4 weeks or 20 weeks after starting ZAH administration. (A, B) A total of 81.3% (26/32) of the CD patients did not undergo changes in treatment other than ZAH from 4 weeks before to 4 weeks after starting ZAH administration. The median serum zinc levels significantly improved from 57.0 μg/dL (31–74) to 91.0 μg/dL (43–171) (P<0.001). Median CDAI scores significantly improved from 145 (43–546) to 116 (36–397) (P=0.003). (C, D) A total of 76.0% (19/25) of CD patients did not undergo changes in treatment other than ZAH from 4 weeks before to 20 weeks after starting ZAH administration. The median serum zinc levels significantly improved from 59.0 μg/dL (46–73) to 85.0 μg/dL (58–189) (P<0.001). Median CDAI scores significantly improved from 170 (21–430) to 109 (21–425) (P=0.004).

  • Fig. 4. Correlation between serum zinc level and Crohn’s Disease Activity Index (CDAI) score or C-reactive protein (CRP) in Crohn’s disease (CD) patients. (A, B) Before zinc acetate hydrate (ZAH) administration, there was a moderate correlation between serum zinc level and CDAI score (r=–0.439, P=0.005), and there was a moderate correlation between serum zinc level and CRP (r=–0.483, P=0.002). (C, D) Four weeks after ZAH administration, there was no correlation between the degree of increase in serum zinc level and the degree of improvement in CDAI score (r=–0.020, P=0.913), and there was no correlation between the degree of increase in serum zinc level and the degree of improvement in CRP (r=–0.047, P=0.800). (E, F) Twenty weeks after ZAH administration, there was no correlation between the degree of increase in serum zinc level and the degree of improvement in CDAI score (r=–0.301, P=0.148), and there was no correlation between the degree of increase in serum zinc level and the degree of improvement in CRP (r=–0.090, P=0.668).

  • Fig. 5. Changes in serum zinc level and partial Mayo score in ulcerative colitis (UC) patients before zinc acetate hydrate (ZAH) administration and 4 weeks or 20 weeks after administration. (A, B) There were 9 UC patients whose serum zinc levels were measured 4 weeks after ZAH administration. Median serum zinc levels significantly improved from 63.0 μg/dL (57–74) to 94.0 μg/dL (53–146) (P=0.020). Median partial Mayo scores improved from 3 (0–9) to 1 (0–4) (P=0.125). (C, D) There were 5 UC patients whose serum zinc levels were measured 20 weeks after ZAH administration. Median serum zinc levels significantly improved from 63.0 μg/dL (57–73) to 94.0 μg/dL (62–109) (P=0.125). Median partial Mayo scores before and after ZAH administration improved from 3 (0-5) to 1 (0-3) (P=0.688).


Reference

1. Mekhjian HS, Switz DM, Melnyk CS, Rankin GB, Brooks RK. Clinical features and natural history of Crohn’s disease. Gastroenterology. 1979; 77(4 Pt 2):898–906.
Article
2. Harries AD, Heatley RV. Nutritional disturbances in Crohn’s disease. Postgrad Med J. 1983; 59:690–697.
Article
3. Dawson AM. Nutritional disturbances in Crohn’s disease. Br J Surg. 1972; 59:817–819.
Article
4. Dawson AM. Nutritional disturbances in Crohn’s disease. Proc R Soc Med. 1971; 64:166–170.
5. Hwang C, Ross V, Mahadevan U. Micronutrient deficiencies in inflammatory bowel disease: from A to zinc. Inflamm Bowel Dis. 2012; 18:1961–1981.
Article
6. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019; 68(Suppl 3):s1–s106.
Article
7. Walsh CT, Sandstead HH, Prasad AS, Newberne PM, Fraker PJ. Zinc: health effects and research priorities for the 1990s. Environ Health Perspect. 1994; 102 Suppl 2(Suppl 2):5–46.
Article
8. Filippi J, Al-Jaouni R, Wiroth JB, Hébuterne X, Schneider SM. Nutritional deficiencies in patients with Crohn’s disease in remission. Inflamm Bowel Dis. 2006; 12:185–191.
Article
9. Vagianos K, Bector S, McConnell J, Bernstein CN. Nutrition assessment of patients with inflammatory bowel disease. JPEN J Parenter Enteral Nutr. 2007; 31:311–319.
Article
10. Solomons NW, Rosenberg IH, Sandstead HH, Vo-Khactu KP. Zinc deficiency in Crohn’s disease. Digestion. 1977; 16:87–95.
Article
11. Siva S, Rubin DT, Gulotta G, Wroblewski K, Pekow J. Zinc deficiency is associated with poor clinical outcomes in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2017; 23:152–157.
Article
12. McClain C, Soutor C, Zieve L. Zinc deficiency: a complication of Crohn’s disease. Gastroenterology. 1980; 78:272–279.
Article
13. Sturniolo GC, Molokhia MM, Shields R, Turnberg LA. Zinc absorption in Crohn’s disease. Gut. 1980; 21:387–391.
Article
14. Naber TH, van den Hamer CJ, Baadenhuysen H, Jansen JB. The value of methods to determine zinc deficiency in patients with Crohn’s disease. Scand J Gastroenterol. 1998; 33:514–523.
Article
15. Tomita H. A proposal of the clinical standard value for diagnose of zinc deficiency by serum zinc value. Biomed Res Trace Elem. 2008; 19:22–24.
16. Matsuoka K, Kobayashi T, Ueno F, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol. 2018; 53:305–353.
Article
17. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: a randomized study. N Engl J Med. 1987; 317:1625–1629.
Article
18. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. National Cooperative Crohn’s Disease Study. Gastroenterology. 1976; 70:439–444.
19. Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn’s Disease Activity Index (CDAI). Gastroenterology. 1979; 77(4 Pt 2):843–846.
Article
20. Kobayashi Y, Ohfuji S, Kondo K, et al. Association between dietary iron and zinc intake and development of ulcerative colitis: a case-control study in Japan. J Gastroenterol Hepatol. 2019; 34:1703–1710.
Article
21. Li J, Chen H, Wang B, et al. ZnO nanoparticles act as supportive therapy in DSS-induced ulcerative colitis in mice by maintaining gut homeostasis and activating Nrf2 signaling. Sci Rep. 2017; 7:43126.
Article
22. Itagaki M, Saruta M, Saijo H, et al. Efficacy of zinc-carnosine chelate compound, Polaprezinc, enemas in patients with ulcerative colitis. Scand J Gastroenterol. 2014; 49:164–172.
Article
23. Sturniolo GC, Di Leo V, Ferronato A, D’Odorico A, D’Incà R. Zinc supplementation tightens “leaky gut” in Crohn’s disease. Inflamm Bowel Dis. 2001; 7:94–98.
Article
24. Harzer G, Kauer H. Binding of zinc to casein. Am J Clin Nutr. 1982; 35:981–987.
Article
25. Fleming CR, Huizenga KA, McCall JT, Gildea J, Dennis R. Zinc nutrition in Crohn’s disease. Dig Dis Sci. 1981; 26:865–870.
Article
26. Brewer GJ. Wilson’s disease. In : Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, editors. Harrison’s principles of internal medicine. 16th ed. New York: McGraw-Hill;2005. p. 2313–2315.
27. Illing AC, Shawki A, Cunningham CL, Mackenzie B. Substrate profile and metal-ion selectivity of human divalent metal-ion transporter-1. J Biol Chem. 2012; 287:30485–30496.
Article
28. Kanabrocki EL, Sothern RB, Ryan MD, et al. Circadian characteristics of serum calcium, magnesium and eight trace elements and of their metallo-moieties in urine of healthy middle-aged men. Clin Ter. 2008; 159:329–346.
29. McMillan EM, Rowe DJ. Clinical significance of diurnal variation in the estimation of plasma zinc. Clin Exp Dermatol. 1982; 7:629–632.
Article
30. Food and Nutrition Board, Institute of Medicine. Zinc. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press;2001. p. 442–501.
Full Text Links
  • IR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr