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Arginine Supplementation
and Wound Healing
KELBY BRINK
SODEXO DIETETIC INTERN
JUNE 12TH, 2019
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Activity

 On the note card provided, draw a

picture of the 4 classifications of pressure
ulcers
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Background Information- Pressure Ulcer
Stages
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Background Information- Layers of the
Skin
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Background Information- Wound
Healing Stages
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Background Information

 Wounds affect 2.5 million patients each year

 Pressure Ulcers cost $9.1-$11.6 billion per year
 Costs for individual pressure ulcers range from $20,900-
$51,700 per pressure ulcer

US Dept of Health, 2014

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Background Information

 Topic Selection: from experience at LVHN

 Currently
Juven or similar products are
recommended by some RD’s for patients
with burns or ulcers
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Background Information

 Arginine is one of the 20 amino acids

 Conditionally essential during times of stress
 Broken down to fuel the Krebs Cycle
 Carries
nitrogenous waste out of the body
through urea cycle
 Substrate for nitric oxide production
 Causes blood vessels to open wider
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Background Information

 Building block for collagen synthesis

 Creates new cells
 Food sources
 Red meat, poultry, fish, watermelon,
nuts/seeds, soy protein isolate, dairy
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Learning Objectives

 Participants will be able to explain the

current evidential associations between
arginine and wound healing.
 Participants will be able to provide
patients with evidence-based
recommendations regarding arginine
supplementation in wound healing.
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Presentation Overview

 Arginine in Diabetic and Pressure Ulcer

Healing
 Arginine in Cesarean Section Wound
Healing
 Arginine in Chronic Oral Wound Healing
 Discussion and Conclusion
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Diabetic and
Pressure Ulcers
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Study 1: Arginine in Wound Healing for
Non-Malnourished Patients

Inclusion Criteria Exclusion Criteria Pre-Supplement Wound

Characteristics

• Wounds existing >3 • Recent weight loss • 9 Diabetic Foot Ulcers

weeks • Severe medical • 7 Pressure Ulcers
• Did not improve with conditions • 13 Leg Ulcers
standard wound • Tube fed patients
care • Previous arginine
• Meeting estimated supplementation
energy needs
through oral diet
Neyens, 2017
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Study 1 Continued

 Methods
 One supplement 1-3x daily for 12 weeks
 Must consume 5g of arginine per day
 Measures
 Wound healing through wound surface area
measurements
 Patient satisfaction rating
 Compliance to supplementation
Neyens, 2017
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Study 1 Continued

Neyens, 2017
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Study 1 Continued

 Outcomes
 10 wounds completely healed
 13 wounds with improvement
3 wounds unchanged
 Positive supplementation satisfaction rating
 Limitations
 Small sample size- 29 participants
 Formula with many nutrients
Neyens, 2017
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Study 2- Arginine in Wound Healing for
Diabetic Ulcers

 Prospective, double-blind, randomized, controlled

study
 Inclusion Criteria
 Diabetic foot ulcer for over 30 days but less than 12
months
 Exclusion Criteria
 Uncontrolled diabetes, impaired renal/liver function,
infection, vascular disease

Armstrong, 2014
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Study 2 Continued Group Supplement

Experimental • 80kcals
 Methods
• 7g L-arginine
 Supplement 2x daily • 7g glutamine
 16 weeks • 2.5g protein
• 300mg vit C
 Measures
Control • 88kcals
 Wound area • Low glycemic
 Results response
 No statistically significant difference in outcomes unless baseline
albumin was low
 207 participants: wound area at 16 weeks with p-value of 0.623
Armstrong, 2014
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Study 2 Continued

Control: Black
Circles
Experimental: Red
Squares

Armstrong, 2014
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Study 2 Continued

Group # with Low Wound

Albumin Healing
Experimental 61 50.8%
participants

Control 66 34.9%
participants

 P-value of 0.0325
Armstrong, 2014
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Study 3- Arginine and Collagen
Peptides in Pressure Ulcers

 Inclusion Criteria
 Receiving/consuming 60% of energy needs
 inflammation in wound
 Exclusion Criteria
 Uncontrolled diabetes
 Systemic infection
 Untreatable pressure ulcers
 Hemodialysis
Yamanaka, 2017
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Study 3 Continued

Group Supplement
 Methods
Control Standard Wound
4 weeks of one supplement Care
daily
Collagen 12g protein
 16-18 people per group
Peptide 10g collagen peptide
 Measurement 80kcals
 DESIGN-R method
Arginine 5g protein
 Bywound, ostomy, and
2.5g arginine
continence nurse
100kcals
Yamanaka, 2017
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Study 3 Continued

 Outcomes
 All groups had improvement in wound healing
 Collagen Peptide group had the most improvement
 Arginine group had the fastest improvement
 Improvement slowed after 2 weeks

Yamanaka, 2017
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Study 3 Continued

Yamanaka, 2017
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Cesarean
Section
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Study 4- Arginine in Cesarean Section
Healing

 Case Study
 Patient Background
 28 years old
 Pre-pregnancy BMI of 23.5
 No history of chronic diseases
 C-section at 36 weeks
 Normaldiet consisting of 2-5 servings of fruits,
vegetables, whole grain, protein, and dairy daily
Hicks-Roof, 2018
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Study 4 Continued

 Methods
 Juven supplement 2x daily Supplement
• 80 kcals
2 weeks
• 7g L-arginine
 Measures • 7 g glutamine
 Stony Brook Scar Evaluation Scale • collagen protein,
vitamin C, E, and
 Manchester Scar Scale
zinc
 PCP opinion

Hicks-Roof, 2018
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Study 4 Continued

 Outcomes
 Scars
scored a 5 and 8 on Stony Brooks and
Manchester scar scales respectively
 PerPCP, had improved wound healing compared to
most patients with same procedure
 Limitations
 One person
 PCP opinion for results
Hicks-Roof, 2018
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Chronic Oral
Wounds
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Study 5- Arginine in Healing of Chronic
Soft Tissue Diseases of the Mouth

 Inclusion Criteria
 Participants
with oral lichen planus or recurrent
apthous stomatitis
 Wounds not responding to regular treatment

Inaba, 2016
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Study 5 Continued

 Methods
 One Abound packet daily for 2 weeks
 78kcals,
beta-hydroxyl-beta-methylbutyrate, arginine, and
glutamine
 Measures
 Wound surface area
 Outcomes
 Improvement in 7 out of 9 wounds
 Some wound disappeared after 8 weeks of supplementation
Inaba, 2016
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Study 5 Continued

 Patient 1
• Chronic, non-healing oral wound
• Not improving with standard wound care
• Continued with supplementation for 8 weeks
• All symptoms and wounds disappeared

Inaba, 2016
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Study 5 Continued

 Patient 2
• Chronic, non-healing, and recurring oral wounds
• Not responsive to standard treatment
• Total wound healing after 3 weeks on
supplementation
• No recurring wounds at 6 month follow-up

Inaba, 2016
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Conclusions,
Applications for
Clinical Practice,
and Directions for
Further Research
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Study Summaries

Study Effective? Amount of

Arginine
1: Diabetic and Yes 3g
Pressure Ulcers
2: Diabetic Foot Only with low 7g
Ulcers albumin levels
3: Pressure Ulcers Somewhat 2.5g
4: C-Section Yes 7g
5: Chronic Oral Yes 7g
Wounds
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Literature Review Summaries

 Review based on 11 articles from 2001-2014

 645 total patients with Pressure Ulcers
 3-9g of L-arginine per supplement
 Conclusions: Substantial evidence supporting the
positive effect of arginine supplementation with
protein.
 Limitations:
 Small studies
Neyens, 2017
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Conclusions

 Mixed results as to whether or not arginine by itself is

helpful in wound healing
 Combination of arginine, glutamine, collagen peptides
and other vitamins and minerals have shown to be
most effective
 These mixtures can be helpful in healing many different
types of wounds
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Applications for Clinical Practice

 Supplements with multiple ingredients may benefit

patients with wounds the most
 Important to monitor the patient and effectiveness of
the supplement in order to determine if changes need
to be made
 Dietary interventions can aid in the progression of
wound healing
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Directions for Further Research

 How arginine supplementation alone effects wound

healing
 What combination of ingredients promotes wound
healing the best
 How this supplementation effects patients with different
disease states and conditions
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Emerging Research

 Arginine with metabolic profiling

 Effect of arginine on tumor growth
 Effect of arginine on severe asthma symptoms
 Arginine feeding and its effect on protein metabolism in
cancer patients
 Aspirin and arginine restriction in colorectal cancer

Clinicaltrials.gov
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Questions?
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References

 Neyens, Cereda, Rozsos, Molnár, Rondas, van Leen, Schols (2017). Effects of an Arginine- enriched Oral Nutritional
Supplement on the Healing of Chronic Wounds in Non- Malnurished Patients; A Multicenter Case Series from the
Netherlands and Hungary. Journal of Gerontology and Geriatric Research. 6:2
 Armstrong D., et al. (2014). Treatment Effect of Oral Nutritional Supplementation on Wound Healing in Diabetic Foot
Ulcers: A Prospective Randomized Controlled Trial. Diabetic Medicine, 31 (9): 1069-1077.
 Hicks-Roof K. (2018) The Use of an Arginine-Enriched Oral Nutrition Supplement to Enhance Wound Healing from a
Cesarean Section. Case Reports in Clinical Nutrition. 1:1-7.
 Yamanaka H., Okada S., Sanada H. (2017) A Multicenter, Randomized, Controlled Study of the Use of Nutritional
Supplements containing collagen peptides to facilitate the healing of pressure ulcers. Journal of Nutrition and
Intermediary Metabolism. 8: 51-59.
 Inaba M., et al. (2016). Usefulness of oral administration of the specialized amino acid supplement consisting of b-
hydroxy-b-methylbutyrate, L-arginine, and L-glutamine for chronic soft tissue diseases in the mouth. Journal of Food
Science and Technology. 1(4): 123-127.
 Ellinger, S. (2014). Micronutrients, Arginine, and Glutamine: Does Supplementation Provide an Efficient Tool for
Prevention and Treatment of Different Kinds of Wounds? Journal of Advanced Wound Care. 3 (11): 691-707.
 Clinicaltrials.gov
 Neyens, Cereda, Meijer, Linholm, Schols (2017). Argininge-enriched oral nutrition supplementation in the treatment og
pressure ulcers: A literature Review. Wound Medicine. 16:46-51.
 US Department of Health and Human Services