IBD and decrease AP

Q: 38 years old male with a long-standing history of Inflammatory Bowel Disease (IBD) presented with Right Upper Quadrant (RUQ) pain and suspicion of acute cholecystitis. Serum alkaline phosphatase (AP) is reported to be low, although ultrasound and clinical signs are highly consistent with the diagnosis. What could be the reason for decreased serum alkaline phosphatase in IBD?

Answer: Zinc Deficiency

Patients, particularly those with Crohn's disease, are at high risk of decreased serum zinc concentrations. Additionally, serum zinc levels depend on albumin. Total-body zinc deficiency is associated with reduced serum alkaline phosphatase levels; alkaline phosphatase is a zinc-containing metalloenzyme. 

Overall, patients with zinc deficiency have a higher risk of hospitalization, surgical procedures, and other complications.

IBD patients tend to have clinically significant zinc deficiency, particularly with excessive losses due to ostomies, fistulas, or profuse diarrhea. Additionally, during the active inflammatory state of IBD, there is zinc malabsorption via increased losses of endogenous zinc stores on the one hand and intestinal epithelial sloughing and disruption of reabsorption on the other.

Interestingly, zinc supplementation is found to improve chronic diarrhea in these patients. Some experts suggest supraphysiologic zinc replacement.

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References:

1. McClain C, Soutor C, Zieve L. Zinc deficiency: a complication of Crohn's disease. Gastroenterology 1980; 78:272.

2. Siva S, Rubin DT, Gulotta G, et al. Zinc Deficiency is Associated with Poor Clinical Outcomes in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2017; 23:152.

3. Sturniolo GC, Di Leo V, Ferronato A, et al. Zinc supplementation tightens "leaky gut" in Crohn's disease. Inflamm Bowel Dis 2001; 7:94.

4. Naber TH, Baadenhuysen H, Jansen JB, van den Hamer CJ, van den Broek W. Serum alkaline phosphatase activity during zinc deficiency and long-term inflammatory stress. Clin Chim Acta. 1996 May 30;249(1-2):109-27. doi: 10.1016/0009-8981(96)06281-x. PMID: 8737596.