Effects of L- Carnosine and Its Zinc Complex ( Polaprezinc ) on PU Healing

1. Effects of L-Carnosine and Its Zinc Complex (Polaprezinc) on PU Healing ASPEN- The American Society for Parenteral & Enteral Nutrition Presented by: Emily Macieiski

2. Background Information • Pressure Ulcers (PU) range from a few to 30% of patients in acute and long term care. • Increase mortality rate • Factors that cause them: • Pressure • Advanced age • Malnutrition • Deterioration of underlying dx

4. CAR and Zn • L-carnosine (CAR)- dipeptide composed of B-alanine and L-histidinethat is abundant in long-living cells (muscles and nerves) • Antioxidation, antiglycation, pH buffering, metal ion-chelating, and antiaging activity • Zinc (Zn)- essential trace element required by various enzymes or transcription factors that are involved in cell replication, PRO synthesis, & repair systems after injury • Significant role in wound healing • Deficiency delays wound healing • Excess amounts may inhibit healing and induce Cu and Fe deficiencies

5. PLZ • Polaprezinc (PLZ)- complex consisting of CAR and Zn with 1:1 molar ratio • a synergistic effect of its 2 components on would healing is anticipated • Animal study showed PLZ increased healing of skin incisions • In Europe and US, CAR and PLZ are available as dietary supplements • Aims of this study: • Show effects of CAR and PLZ on PU healing • Show how Zn contributes to PU healing by comparing effects of CAR and PLZ • Examine nutrition status including Zn in patients with PUs

6. Methods • Patients recruited between October 2008- October 2012 from Japan • Inclusion criteria: • At least 20 years old • Must have at least 1 Stage II, III, or IV PU for ≥ 4 wks • ESA for 1 ulcer no more than 24 cm • Capable or oral ingestion • Exclusion criteria: • Presence of clinical suspicion or diagnosis of osteomyelitis • DM, peripheral VD, malignant tumor, acute illness, or severe dx • Being in terminal phase of illness • Use of corticosteroids • Receiving T/P feeding d/t limited ability to consent to study participation

8. Methods cont… • Nonrandomized controlled trial, max 4 week follow up • 42 patients • 14 control • 10PLZ (orally given 2 doses 75 mg/d PLZ – 116 mg CAR + 34 mg Zn) • 18CAR (orally given 2 doses 58 mg/d) • Assessments made 1 x/week for PU severity. • PUSH tool • Risk for PU development assessed by Braden Scale • Ulcer infection controlled during the study

9. Methods cont… • Body weight measurements at week 0 and 4 • Dietary intake recorded for 3 meals/day • Mean intakes of energy, protein, Zn, Cu, Fe, and vitamins A, C, E • Blood biochemistry assessed • CBC, liver fxn tests, transthyretin, CRP, urea, creatinine, electrolytes, uric acid, total and HDL cholesterols, serum Zn, Cu, & Fe • Outcomes: Primary PU healing by PUSH score; Secondary changes in nutritional variables • A P value of <.05 was considered statistically significant.

10. Results • Baseline: • No significant difference in demographic and nutrition parameters, the level of PU risk, and PU characteristics, except for PU location • Most on sacrum • Use of supplements comparable • MWI of PUSH total score: • Control: 0.8 ± 0.2, CAR: 1.6 ± 0.2, PLZ 1.8 ± 0.2

11. Dietary Intakes • No significant differences among the 3 groups in any of these nutrient intakes. • Energy and protein daily intake comparable as well • Vitamins A,C,E- no significant differences among the group

12. Blood biochemistry • After CAR treatment, serum Zn, Cu, Fe showed no significant changes • After PLZ treatment, serum Zn gradually and significantly increased, whereas serum Cu gradually and significantly decreased, serum Fe showed no changes • Serum transthyretin and albumin levels below RR. CRP elevated. No significant changes in any. • On average, CBC, liver fxn tests (except serum albumin), urea, creatinine, electrolytes, uric acid, and total and HDL cholesterol showed little deviation from RR, with no significant changes

13. Discussion • First controlled clinical trial focusing on CAR or PLZ for treatments of PUs. • PU healed 2-2.2x more during the trial than the control group • No significant differences between the effects of the 2 agents • Even though the effects of PLZ were greater than those of CAR • Few studies done to show effects of oral Zn alone • Couldn’t show how Zn alone helped with healing since the complex PLZ was used • 36/42 in the study were already Zn deficient • Serum Zn gradually  after 4 wks d/t PLZ • CAR did not affect serum Zn

14. Discussion cont… • PLZ caused serum Cu to significantly • Before: 65 ug/dL  48 in one pt • Prolonged use can cause anemia • No pt experienced GI distress, impaired immune fxn, or HDL chol d/t high-dose Zn use • Compromised nutrition status (recent wt loss, underweight, reduced oral intake) are risk factors for PUs. • 31% significant wt loss, 69% underweight, 74% underweight at end • Avg 38.19 kcal/kg & 1.52 g PRO/kg

15. Discussion cont… • This study had high frequency of underweight patients ( cytokines in schizophrenia) that possibly triggered hypercatabolism and muscle wasting • Ex: low serum albumin levels and high CRP • Energy requirements may have needed to be more than the recommended • Energy, protein, Cu, Fe, vitamins A, C, E related to PU healing, but intake of these didn’t differ significantly • Limitations: small sample size, lack of randomization, nonblinded, supplements • Conclusion: Results show that CAR and its Zn complex PLZ may be almost equally promising treatments for PUs. • Shortened healing time- costs and improve quality of life

16. Thought of the Day??? • What as health professionals can we do to help treat pressure ulcers?