Vitamins that may be helpful
Antioxidants such as vitamin C, vitamin E, and glutathione are depleted in healing skin
tissue.3 One animal study found that vitamin E (alpha-tocopherol) applied to the
skin shortened the healing time of skin ulcers.4 Another animal study reported that
administration of oral vitamin E before skin lesions were introduced into the skin prevented
some of the tissue damage associated with the development of pressure ulcers.5 A
controlled human trial found that 400 IU of vitamin E daily improved the results of skin graft
surgery for chronic venous ulcers.6 No further research has investigated the
potential benefit of vitamin E for skin ulcers.
Animal research has suggested that vitamin C may help prevent skin ulcers,7 and
in a preliminary study,8 elderly patients with pressure ulcers had lower blood
levels of vitamin C than did ulcer-free patients. Supplementation with vitamin C (3 grams per
day) increased the speed of healing of leg ulcers in patients with a blood disorder called thalassemia, according to a double-blind
study.9 And while a double-blind trial of surgical patients with pressure ulcers
found that supplementation with 500 mg of vitamin C twice a day accelerated ulcer
healing,10 a similar double-blind trial found no difference in the effectiveness of
either 20 mg per day or 1,000 mg per day of vitamin C.11
An older preliminary report suggested that large amounts of folic acid given both orally and by injection could
promote healing of chronic skin ulcers due to poor circulation.12 No controlled
research has further investigated this claim.
A controlled trial found that topical application of a hyaluronic acid compound with compression bandaging
was significantly better than bandaging alone for healing chronic venous skin
ulcers.13 No research has investigated whether oral hyaluronic acid supplements
might be similarly effective.
Zinc plays an important role in tissue
growth processes important for skin ulcer healing. One study reported that patients with
pressure ulcers had lower blood levels of zinc and iron than did patients without pressure
ulcers,14 and preliminary reports suggested zinc supplements could help some types
of skin ulcer.15 Supplementation with 150 mg of zinc per day improved healing in a
preliminary study of elderly patients suffering from chronic leg ulcers.16
Double-blind trials using 135 to 150 mg of zinc daily have shown improvement17 only
in patients with low blood zinc levels,18 and no improvement in leg ulcer
healing.19 20 A double-blind trial of 150 mg zinc per day in people with
skin ulcers due to sickle cell anemia found that the healing rate was almost three times
faster in the zinc group than in the placebo group after six months.21 Lastly, a
preliminary study of patients with skin ulcers due to leprosy found that 50 mg of zinc per day
in addition to anti-leprosy medication resulted in complete healing in most patients within 6
to 12 weeks.22 Long-term zinc supplementation at these levels should be accompanied
by supplements of copper and perhaps calcium, iron, and magnesium. Large amounts of zinc (over
50 mg per day) should only be taken under the supervision of a doctor.
Topically applied zinc using zinc-containing bandages has improved healing of leg ulcers in
double-blind studies of both zinc-deficient23 and elderly individuals.24
Most controlled comparison studies have reported that these bandages are no more effective
than other bandages used in the conventional treatment of skin ulcers,25
26 but one controlled trial found non-elastic zinc bandages superior to alginate
dressings or zinc-containing elastic stockinettes.27 Two controlled trials of
zinc-containing tape for foot ulcers due to leprosy concluded that zinc tape was similarly
effective, but more convenient than conventional dressings.28 29
Pressure ulcers and diabetic ulcers frequently develop in malnourished and/or
institutionalized people. A double-blind study30 of malnourished people compared
topical application of 20 ml of a solution containing essential fatty acids (EFAs) and
linoleic acid extracted from sunflower oil with a control solution containing topical mineral
oil. Each solution was applied to the skin three times per day. Compared with the control
solution, the solution containing EFAs significantly reduced the incidence of pressure ulcers
and improved the hydration and elasticity of the skin.
A preliminary report suggested that evening
primrose oil improves blood flow to the legs and heals or reduces the size of venous leg
ulcers.31 No controlled research has further investigated this claim.
A double-blind trial found that a combination of 900 mg per day of diosmin and 100 mg per
day of hesperidin, two members of the
flavonoid family, resulted in significantly greater healing of venous leg ulcers after two
months.32 33 Related flavonoids known as hydroxyethylrutosides have also
been investigated for venous ulcer healing. While one controlled study reported significant
additional benefit when 2,000 mg per day of hydroxyethylrutosides were added to compression
stocking therapy,34 another double-blind trial using 1,000 mg per day found no
effect on ulcer healing;35 a second double-blind trial found no effect of 1,000 mg
per day hydroxyethylrutosides on the prevention of venous ulcer recurrences.36
Are there any side effects or interactions?
Refer to the individual supplement for information about any side effects or interactions.
1. Breslow RA, Hallfrisch J, Guy DG, et al. The importance of dietary
protein in healing pressure ulcers. J Am Geratr Soc 1993;41:357–62.
2. Bourdel-Marchasson I, Barateau M, Rondeau V, et al. A multi-center
trial of oral nutritional supplementation in critically ill older inpatients.
3. Houwing R, Overgoor M, Kon M, et al. Pressure-induced skin lesions in
pigs: reperfusion injury and the effects of vitamin E. J Wound Care
4. Lucero MJ, Vigo J, Rabasco AM, et al. Protection by alpha-tocopherol
against skin necrosis induced by doxorubicin hydrochloride. Pharmazie
5. Shukla A, Rasik AM, Patnaik GK. Depletion of reduced glutathione,
ascorbic acid, vitamin E, and antioxidant defence enzymes in a healing cutaneous wound.
Free Radic Res 1997;26:93–101.
6. Ramasastry, SS, Angel MF, Narayanan K, et al. Biochemical evidence of
lipoperoxidation in venous stasis ulcer: Beneficial role of vitamin E as antioxidant. Ann
NY Acad Sci 1989; 506–8.
7. Hajarizadeh H, Lebredo L, Barrie R, Woltering EA. Protective effect of
doxorubicin in vitamin C or dimethyl sulfoxide against skin ulceration in the pig. Ann
Surg Oncol 1994;1:411–4.
8. Goode HF, Burns E, Walker BE. Vitamin C depletion and pressure sores
in elderly patients with femoral neck fracture. BMJ 1992;305:935–7.
9. Afifi AM, Ellis L, Huntsman RG, Said MI. High dose ascorbic acid in
the management of thalassaemia leg ulcers—a pilot study. Br J Dermatol
10. Taylor TV, Rimmer S, Day B, et al. Ascorbic acid supplementation in
the treatment of pressure cores. Lancet 1974;ii:544–6.
11. ter Riet G, Kessels AG, Knipschild PG. Randomized clinical trial of
ascorbic acid in the treatment of pressure ulcers. J Clin Epidemiol
12. Kopjas TL. Effect of folic acid on collateral circulation in diffuse
chronic arteriosclerosis. J Am Geriatr Soc 1966;14:1187–92.
13. Taddeucci P, Pianigiani E, Colletta V, et al. An evaluation of
Hyalofill-F plus compression bandaging in the treatment of chronic venous ulcers. J Wound
14. Williams CM, Lines CM, McKay EC. Iron and zinc status in multiple
sclerosis patients with pressure sores. Eur J Clin Nutr 1988;42:321–8.
15. Greaves MW, Skillen AW. Effects of long-continued ingestion of zinc
sulphate in patients with venous leg ulceration. Lancet 1970;2:889–91.
16. Carruthers R. Oral zinc sulphate in leg ulcers. Lancet
17. Haeger K, Lanner E, Magnusson PO. Oral zinc sulfate in the treatment
of venous leg ulcers. In: Pories WJ, Strain WH, Hwu JM, et al (eds), Clinical applications
of zinc metabolism. Springfield, IL: CC Thomas, 1974, 158–67.
18. Hallbook T, Lanner E. Serum-zinc and healing of venous leg ulcers.
19. Greaves MW, Ive FA. Double-blind trial of zinc sulphate in the
treatment of chronic venous leg ulceration. Br J Dermatol 1972;87:632–4.
20. Clayton RJ. Double-blind trial of oral zinc sulphate in patients with
leg ulcers. Br J Clin Pract 1972;26:368–70.
21. Serjeant GR, Galloway RE, Gueri MC. Oral zinc sulphate in sickle-cell
ulcers. Lancet 1970;2:891–3.
22. Mathur NK, Bumb RA. Oral zinc in the trophic ulcers of leprosy.
Int J Lepr 1983;51:410–1.
23. Agren MS. Studies on zinc in wound healing. Acta Derm Venerol
24. Stromberg HE, Agren MS. Topical zinc oxide treatment improves
arterial and venous leg ulcers. Br J Dermatol 1984;111:461–8.
25. Eriksson G. Comparison of two occlusive bandages in the treatment of
venous leg ulcers. Br J Dermatol 1986;114:227–30.
26. Agren MS, Stromberg HE. Topical treatment of pressure ulcers. A
randomized comparative trial of Varidase and zinc oxide. Scand J Plast Reconstr Surg
27. Stacey MC, Jopp-Mckay AG, Rashid P, et al. The influence of dressings
on venous ulcer healing—a randomised trial. Eur J Vasc Endovasc Surg
28. Soderberg T, Hallmans G, Stenstrom S, et al. Treatment of leprosy
wounds with adhesive zinc tape. Lepr Rev 1982;53:271–6.
29. Walton RT, Fritschi EP, Umapathy VA. Treatment of plantar ulcers in
leprosy patients in the community with adhesive zinc tape. Lepr Rev
30. Declair V. Usefulness of topical application of essential fatty acids
to prevent pressure ulcers. Ostomy Wound Management 1997;43:48–52.
31. Simpson LO, Hand BI, Olds RJ. Large leg ulcers, Efamol and hyperbaric
oxygen. N Z Med J 1986;99:552 [abstract].
32. Guilhou JJ, Fevrier F, Debure C, et al. Benefit of a 2-month
treatment with a micronized, purified flavinoidic fraction on venous ulcer healing. A
randomized, double-blind, controlled versus placebo trial. Int J Micro
Clin Exp 1997;17:21–6.
33. Guilhou JJ, Dereure O, Marzin L, et al. Efficacy of Daflon 500 mg in
venous leg ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107
patients. Angiology 1997;48:77–85.
34. Stegmann W, Hubner K, Deichmann B, Muller B. Efficacy of
O-(s-hydroxyethyl)-rutosides in the treatment of venous leg ulcers. Phlebologie
1987;40:149–56 [in French].
35. Mann RJ. A double blind trial of oral O. B-hydroxyethyl rutosides for
stasis leg ulcers. Br J Clin Pract 1981;35:79–81.
36. Wright DD, Franks PJ, Blair SD, et al. Oxerutins in the prevention of
recurrence in chronic venous ulceration: randomized controlled trial. Br J Surg
37. Marquart FX, Bellon G, Gillery P, et al. Stimulation of collagen
synthesis in fibroblast cultures by a triterpene extracted from Centella asiatica.
Connective Tissue Res 1990;24:107–20.
38. Tenni R, Zanaboni G, De Agostini MP, et al. Effect of the
triterpenoid fraction of Centella asiatica on macromolecules of the connective matrix
in human skin fibroblast cultures. Ital J Biochem 1988;37:69–77.
39. Shukla A, Rasik AM, Jain GK, et al. In vitro and in vivo wound
healing of asiaticoside isolated from Centella asiatica. J
40. Brinkhaus B, Linder M, Schuppan D, Hahn EG. Chemical, pharmacological
and clinical profile of the East Asian medicinal plant Centella asiatica.
41. Zawahry ME, Hegazy MR, Helal M. Use of aloe in treating leg ulcers
and dermatoses. Int J Dermatol 1973;12:68–73.
42. Thomas DR, Goode PS, LaMaster K, Tennyson T. Acemannan hydrogel
dressing versus saline dressing for pressure ulcers. A randomized, controlled trial. Adv
Wound Care 1998;11:273–6.
43. Hammarlund C, Sundberg T. Hyperbaric oxygen reduced size of chronic
leg ulcers: a randomized double-blind study. Plast Reconstr Surg
44. Wattel F, Mathieu D, Coget JM, Billard V. Hyperbaric oxygen therapy
in chronic vascular wound management. Angiology 1990;41:59–65.
45. Lee HC, Niu KC, Chen SH, et al. Hyperbaric oxygen therapy in clinical
application. A report of a 12-year experience. Chung Hua I Hsueh Tsa Chih (Taipei)
46. Landau Z. Topical hyperbaric oxygen and low energy laser for the
treatment of diabetic foot ulcers. Arch Orthop Trauma Surg 1998;117:156–8.
47. Heng MC, Pilgrim JP, Beck FW. A simplified hyperbaric oxygen
technique for leg ulcers. Arch Dermatol 1984;120:640–5.
48. Leslie CA, Sapico FL, Ginunas VJ, Adkins RH. Randomized controlled
trial of topical hyperbaric oxygen for treatment of diabetic foot ulcers. Diabetes
49. Faglia E, Favales F, Aldeghi A, et al. Adjunctive systemic hyperbaric
oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized
study. Diabetes Care 1996;19:1338–43.
50. Baroni G, Porro T, Faglia E, et al. Hyperbaric oxygen in diabetic
gangrene treatment. Diabetes Care 1987;10:81–6.
51. Frantz RA. Adjuvant therapy for ulcer care. Clin Geriatr Med
52. Frantz RA. Adjuvant therapy for ulcer care. Clin Geriatr Med