Tag Archives: zinc

Time to Revise ImproveCareNow Micronutrient Recommendations

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With ImproveCareNow, there have been efforts to minimize variation in care.  As such, there have been suggestions to monitor labs like vitamin D, vitamin B12, and folate routinely. I have voiced concern that some of this testing is unnecessary.  For vitamin B12, deficiency in pediatrics is rare; at risk populations include those with extensive small bowel resections, gastric resections or strict vegan diet.

A recent article (J Fritz et al. Inflamm Bowel Dis 2019; 25: 445-59) which is a systematic review of micronutrients in pediatric inflammatory bowel disease provides further support for the approach of less testing.

Key points:

  • A total of 39 studies were included in the final review (2903 subjects, 1115 controls)
  • Iron deficiency and vitamin D deficiency are common in pediatric patients with IBD
  • Vitamin B12 and folate deficiency are rare
  • Zinc deficiency is uncommon but increased in patients with Crohn’s disease compared to healthy controls.
  • The authors recommend routine (at least yearly) testing for iron, vitamin D and zinc and that there is “insufficient evidence to support routine screening for other micronutrient deficiencies.”

My take: Except in patients with surgical resections and in those with unusual diets (eg. vegan), routinely checking vitamin B12, folate and most other micronutrients is unnecessary & low value care.

Related blog posts:

Vitamin B12:

Vitamin D:

Iron:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

How Effective is Zinc Therapy for Wilson’s Disease?

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A study from France (R Santiago et al. JPGN 2015; 61: 613-18) examined the use of zinc therapy for Wilson’s disease. Though the national survey had 90 children from 6 centers, there were only 26 who were treated with zinc and only 9 who had received zinc as a first-line single therapy.

Despite the small numbers, data on treating children with Wilson’s disease are fairly sparse; as such, this article provides some helpful information.

The study reviews zinc’s mechanism of action:

“Oral zinc induces enterocyte synthesis of metallothionein, a cystic-rich protein acting as an endogenous chelator for metals, which preferentially binds copper in the enterocyte and inhibits its entry into the portal circulation. Thereby, it reduces copper intestinal absorption and leads to copper elimination in fecal contents within senescent enterocytes.”

Key results:

  • “Median transaminase level normalized within 6 months from treatment initiation” in the entire cohort of 26 children.  However, 10 of 26 children had abnormal ALT at 6 months into therapy.
  • Zinc dose was gradually increased such that 38% eventually had doses “exceeding recommended doses” which were >75 mg/day in 6-15 years and >150 mg/day in those ≥16 years.
  • Overall, the authors thought that zinc appeared to be less effective.  Failure with zinc occurred in 5 of 9 (3 due to ineffectiveness, 2 due to poor adherence).  The authors note that decompensation has been reported in children and adults on zinc monotherapy.

The authors indicate that zinc therapy is likely most appropriate after an induction phase with chelators in most children.  Criteria for changing to zinc include the following: “patients should be clinically well…with normal transaminase levels and hepatic synthetic function, non-ceruloplasmin-bound copper concentration within the normal range, and 24-hour urinary copper excretion in the range of 200-500 mcg/24 h.”

Additional precautions with zinc acetate (which is often better tolerated than chelators), 4 of 26 children in this study had gastric irritation, including one child with a perforation.  Therefore, a low threshold for endoscopy should be set in a child with epigastric pain. Adherence can be problematic due to the timing & frequency (TID) of zinc administration.  Monitoring urinary zinc excretion can be useful to monitor compliance.

Related blog posts:

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“This Is A Stick Up — Your Money or Your Life”

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When I read a recent Hepatology editorial (Hepatology 2015; 61: 1106-8), I could not help think of the aforementioned title of this blog.

Here’s the scoop:

The two most commonly used medications for Wilson’s disease are trientine (Syprine) and D-penicillamine (Cupramine). For about 20 years, the original manufacturer of these medications kept the consumer cost at ~$1 per 250 mg tablet.  Currently the cost of Syprine is ~$200 per 250 mg tablet and Cuprimine costs ~$55 per 250 mg tablet.  This 200-fold increase translates into a yearly cost of ~$300,000.

How did this happen?

  • Little competition
  • Profit motive
  • Patients are reluctant to protest (they need this medication to be manufactured)

Why is this outrageous?

This increase in cost was not driven by any new discovery or research innovation.

Are there options?

Zinc is inexpensive and may be an option after initial period of chelation/normalization of liver biochemistries.  Zinc needs to be taken two to three times per day and “well away from meals for best absorption.”

Bottomline: These medication prices are outrageous.

Briefly noted:

  • “Molecular pathophysiology of portal hypertension”  Hepatology 2015; 61: 1406-15. Terrific review with excellent figures.
  • “Ezetimibe for the treatment of Nonacloholic Steatohepatitis” (MOZART trial) Hepatology 2015; 61: 1239-50. This randomized double-blind, placebo-controlled trial with 50 patients (biopsy-proven NASH) showed that Ezetimbe was not significantly different from placebo in histologic response rates, serum aminotransferases, or in magnetic resonance elastography findings.
  • Van Biervliet et al. “Clinical Zinc Deficiency as Early Presentation of Wilson Disease” JPGN 2015; 60: 457-9. Case report.

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What happens to micronutrient levels in the hospital setting?

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When atypical labs need to be obtained, many times this is easier in the hospital setting for logistical reasons including insurance and accessibility to specialty labs.  One group of labs that may be less suited for checking in the hospital, despite convenience, would be micronutrients.  Many of the micronutrients can be affected by systemic inflammatory response (Am J Clin Nutr 2012; 95: 64-71).  Thanks to Kipp Ellsworth for this reference (from his @PedNutritionGuy twitter feed).

Previous studies on systemic inflammatory response (SIR), as assessed by elevated C-reactive protein (CRP) concentrations, has shown that with elective surgery there are transient decreases in plasma concentrations of zinc, selenium, iron, vitamin A, vitamin E, carotenoids, riboflavin, vitamin B-6, vitamin C, and vitamin D.

This current study adds to this body of information.  Between 2001-2011, 2217 whole-blood samples were taken from 1303 patients. Specific micronutrients that were studied: plasma zinc, copper, selenium, vitamins A, B-6, C, and E.  For vitamin D, the authors examined 4327 samples from 3677 patients. The authors did not include manganese, thiamine or riboflavin because these are measured in erythrocytes.

For each analyte, the concentrations were separated according to 6 categories of CRP values: <5, 6-10, 11-20, 21-40, 41-80, and >80 mg/L.

Key finding: Except for copper and vitamin E, all plasma micronutrient concentrations decreased with increasing severity of acute inflammatory response.  For selenium, vitamin B-6, and vitamin C, this occurred with only slight increases in CRP (5 to 10 mg/L).

The magnitude of the SIR effect on micronutrients was quite variable among patients and analytes.  When CRP was >80 mg/L, analyte deficiency rate was noted to be the following:

  • 60 % for selenium (vs. 33% with NL CRP)
  • 48% for vitamin A (vs. 7% with NL CRP)
  • 35% for vitamin B-6 (vs. 14% with NL CRP)
  • 80% for vitamin C (vs. 33% with NL CRP)
  • 88% for vitamin D (vs. 69% with NL CRP)
  • 81% for zinc (vs. 33% with NL CRP)
  • 9% for copper (vs. 4% with NL CRP)
  • 16% for vitamin E (vs. 9% with NL CRP)

**The specific normal value cutoffs and more data at all CRP values are noted in Table 9 of the manuscript.

The implications from this study are clear.  When micronutrient values are derived from plasma during a SIR, a false-positive diagnosis of a micronutrient deficiency is more likely. The study has several limitations and the findings may not be applicable to all types of medical conditions.

Authors conclusion: When CRP concentration is >20 mg/L (>2 mg/dL), “plasma concentrations of selenium, zinc, and vitamins A, B-6, C, and D are clinically uninterpretable.”

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