1. ASPEN- The American Society for Parenteral & Enteral Nutrition
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- histidine that 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
Glycation- covalent bonding of PRO/lipid molecule with a sugar molecule. Impairs functioning of biomolecules.
CAR- has life-extending effects on fibroblasts, stimulatory effect on nitric oxide production in endothelial cells, and protective effect against oxidative stress implicated in the pathogenesis of nonhealing ulcers.
No study has found oral zinc supplementation to have a + effect on PU healing

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 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
Administered until healing or max 4 weeks
Throughout, all patients received same topical treatment and PU care, all given their regular diets and prescriptions
Some received high PRO and energy supplements to meet their needs
PUSH (pressure ulcer scale for healing) used for rating. 0 (completely healed) to 17 (greatest severity).
Braden Scale- 6 (highest risk) to 23 ( lowest risk)
Local pressure reduced by using repositioning, alternating pressure air mattress on the bed, and pressure redistributing seat cushion when sitting in a chair. Topical treatment also given.
When the study started, granulation tissues were removed as extensively as possible

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.
Intake recorded on a scale 0 (nothing consumed) to 10 (all consumed) for each individual food/beverage item.
These were put in manually using the Standard Tables of Food Composition in Japan.
All blood taken in fasted state

10. Results Baseline: MWI of PUSH total score:
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
Contrary to their expectation that Zn-containing PLZ would show a great advantage over CAR
Even in those few studies, no significant effects found using Zn sulfate at a dosage of about 150 mg/dl of elemental Zn.
Difficult to determine Zn status, even using serum Zn level which is most often used approach. Still poor measure of Zn deficiency

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 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?