What is the application of integrative medicine in dermatology?

1. INTEGRATIVE MEDICINE
in DERMATOLOGY:
What is the evidence?
Peter Nugraha Soekmadji
Department of Dermatovenereology
Faculty of Medicine
Maranatha Christian University
Bandung
peternugraha@yahoo.com

2. Conflict of Interest Statement
• NO support or commercial funding for this
presentation or for any products mentioned
here

3. TOPICS OUTLINE
1. Introduction
2. General skin care
3. Sun protection
4. Acne
5. Hair loss
6. Hyperpigmentation disorders

4. Integrative Dermatology
• Complementary / alternative / integrative
medicine?
• Is it evidence-based?
– Efficacy
– Safety
• Is it feasible?

5. “Satius est enim anceps auxilium
experiri quam nullum”
(It is better to try a doubtful remedy
than none at all)
Celsus

6. “Primum non nocere”
(First do no harm)
Hippocratic oath

8. Topical Vitamin C
• Tissue inhibitor of matrix metalloproteinase ↓
• Collagen ↑
• Better skin texture
• Dyspigmentation & rhytides ↓
1. Split-face study of topical 23.8% l-ascorbic acid serum in treating photo-aged skin. J Drugs Dermatol. 2012 Jan;11(1):51–56.
2. Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix
metalloproteinase I in the human dermis. J Invest Dermatol. 2001 Jun;116:853–59.

9. Oral Flavonoids
100 g of dark chocolate daily
• UV-induced erythema ↓
• Cutaneous microcirculation ↑
• Skin hydration ↑
• Better skin texture
1. Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition in women. J
Nutr. 2006 Jun;136(6):1565–9.
2. Consumption of flavanol-rich cocoa acutely increases microcirculation in human skin. Eur J Nutr. 2007 Feb;46(1):53–56.

10. Oral/Topical Soy
• MMP ↓
• Hyaluronic acid production ↑
• Fine wrinkles↓
• Skin elasticity ↑
1. Oral intake of soy isoflavone aglycone improves the aged skin of adult women. J Nutr Sci Vitaminol (Tokyo). 2007;53(1):57–62.
2. Efficacy of a soy moisturizer in photoaging: adouble-blind, vehicle-controlled, 12-week study. J Drugs Dermatol. 2007;6(9):917–22.

11. Oral Carotenoids
Tomato paste
• UV-induced erythema ↓
• MMP ↓
• Mitochondrial DNA
damage ↓
• Collagen ↑
1. Dietary tomato paste protects against ultraviolet light-induced erythema in humans. J Nutr. 2001 May;13(5):1449–51.
2. Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial. Br J Dermatol. 2011
Jan;164(1):154–62.

12. Handbook of Integrative Dermatology: An Evidence-Based Approach

14. Oral/Topical Niacinamide
• Actinic keratosis (premalignant lesion) ↓
• Photosensitivity & photocarcinogenesis ↓
1. Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatol Surg. 2005 Jul;7(2):860–5.
2. Oral nicotinomide reduces actinic keratosis in phase II double blinded randomized controlled trials. J Invest Dermatol. 2012;132:1497–500.

15. Oral Polyphenols
Green tea, wine, curcumin
• UV-induced erythema ↓
• ROS ↓
• Pirymidine dimers ↓
• Photocarcinogenesis ↓
• Matrix metalloproteinase (MMP) ↓
1. Effects of oral epigallocatechin gallate supplementation on the minimal erythema dose and UV-induced skin damage. Skin Pharmacol
Physiol. 2009;22(3):137–41.
2. Curcumin inhibits UV radiation-induced skin cancer in SKH-1 mice. Otolaryngol Head Neck Surg. 2013;148:797–803.

16. Topical Green Tea
1. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. J Am Acad Dermatol. 2001 Mar;44(3):425–32.
2. Green tea polyphenol treatment to human skin prevents formation of ultraviolet light B-induced pyrimidine dimers in DNA. Clin Cancer Res.
2000 Oct;6:3864–69.

17. Oral Green Tea
1. Effects of oral epigallocatechin gallate supplementation on the minimal erythema dose and UV-induced skin damage. Skin
Pharmacol Physiol. 2009;22(3):137–41.

18. Curcumin
2. Curcumin inhibits UV radiation-induced skin cancer in SKH-1 mice. Otolaryngol Head Neck Surg. 2013;148:797–803.
3. Polyphenols: skin photoprotection and inhibition of photocarcinogenesis. Mini Rev Med Chem. 2011 Dec;11(14):1200–15.

19. Oral Carotenoids
40 g of tomato paste daily
• Lipid peroxidation & singlet oxygen ↓
• UV-induced erythema ↓
1 . β-Carotene and other carotenoids in protection from sunlight. Am J Clin Nutr. 2012Nov;96(5):1179S–84S.
2. Photosensitivity disorders in children: part I. J Am Acad Dermatol. 2012 Dec;67(6):1093
3. Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial. Br J Dermatol.

20. Polypodium leucotomos
Oral supplement
• Apoptosis ↓
• DNA repair ↑
• UV-induced immunosuppression ↓
• Polymorphous light eruption, actinic keratosis,
squamous cell carcinoma ↓
1. Orally administered Polypodium leucotomos extract decreases psoralen UVA-induced phototoxicity, pigmentation, and damage of human
skin. Middelkamp-Hup MA, Pathak MA, Parrado C, Garcia-Caballero T, Rius-Diaz F, Fitzpatrick T, Gonzalez S. J Am Acad Dermatol. 2004;50:41–9.
2. Oral administration of Polypodium leucotomos delays skin tumor development and increases epidermal p53 expression and the antioxidant

21. PUVA vs PL Repigmentation (4 months)
1. Orally administered Polypodium leucotomos extract decreases psoralen UVA-induced phototoxicity, pigmentation, and damage of human
skin. Middelkamp-Hup MA, Pathak MA, Parrado C, Garcia-Caballero T, Rius-Diaz F, Fitzpatrick T, Gonzalez S. J Am Acad Dermatol. 2004;50:41–9.

22. Handbook of Integrative Dermatology: An Evidence-Based Approach

24. Topical Vitamin C
• Antimicrobial effects → P. acnes ↓
• Antioxidant → sebum oxidation ↓
• Stability?
1. Comparison of clinical efficacies of sodium ascorbyl phosphate, retinol and their combination in acne treatment. Int J Cosmet Sci. 2009
Feb;31(1):41–6.
2. Sodium L-ascorbyl-2-phosphate 5% lotion for the treatment of acne vulgaris: a randomized,double-blind, controlled trial. J Cosmet

25. 1. Comparison of clinical efficacies of sodium ascorbyl phosphate, retinol and their combination in acne treatment. Int J Cosmet
Sci. 2009 Feb;31(1):41–6.
5% MAP
0.2% retinol
Combination

26. 3. Sodium ascorbyl phosphate shows in vitro and in vivo efficacy in the prevention and treatment of acne vulgaris. Int J Cosmet
Sci. 2005 Jun;27(3):171–6.

27. Topical Niacinamide
• Antioxidant
• Sebum production ↓
• IL-8 production ↓ → inflammation ↓
• Efficacy ≈ topical clindamycin, without
bacterial resistance
1. Topical 4% nicotinamide vs 1% clindamycin in moderate inflammatory acne vulgaris. Int J Dermatol. 2013;52:999–1004.
2. Topical clindamycin 1% vs linoleic acid-rich phosphatidylcholine and nicotinamide 4% in the treatment of acne: a multicenter-randomized
trial. Int J Cosmet Sci. 2011 Oct;33(5):467–76.

28. 1. Topical 4% nicotinamide vs 1% clindamycin in moderate inflammatory acne vulgaris. Int J Dermatol. 2013;52:999–1004.
1% clindamycin
4% nicotinamide

29. Dietary Modifications
• Association:
– Dairy products (skim milk & ice cream)
– High glycemic load foods
• Protective:
– Fish
– Lower body mass index
1. High glycemic load diet, milk and ice cream consumption are related to acne vulgaris in Malaysian young adults: a case control study. BMC
Dermatol. 2012;12:13.
2. Mediterranean diet and familial dysmetabolism as factors influencing the development of acne. Scand J Pub Health 2012;40:466–474.

30. 1. High glycemic load diet, milk and ice cream consumption are related to acne vulgaris in Malaysian young adults: a case control
study. BMC Dermatol. 2012;12:13.

31. 7. The effect of a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters
associated with acne vulgaris: a randomized, investigator-masked, controlled trial. J Am Acad Dermatol. 2007 Aug;57(2):247–56.

32. Topical Tea Tree Oil
• Disruption of bacterial membranes →
antiseptics
• Vs benzoyl peroxide: slower onset, irritation ↓
1. The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: A randomized, double-blind placebo-controlled study. Indian J
Dermatol Venereol Leprol. 2007;73(1):22–25.
2. A comparative study of tea-tree oil versus benzoyl peroxide in the treatment of acne. RS. Med J Aust. 1990;153(8):455–8.

33. Handbook of Integrative Dermatology: An Evidence-Based Approach

34. Topical Green Tea
• Sebum production ↓
• NF-κB & AP-1 ↓ → inflammation
• Clinical outcome: severity ↓
1. The efficacy of topical 2% green tea lotion in mild-to-moderate acne vulgaris. J Drugs Dermatol. 2009 April;8(4).
2. Outcomes of 3% green tea emulsion on skin sebum production in male volunteers. Bosn J Basic Med Sci. 2010 Aug;10(3):260–4.
3. Epigallocatechin-3-Gallate Improves Acne in Humans by Modulating Intracellular Molecular Targets and Inhibiting P. acnes. J Invest

35. 3. Epigallocatechin-3-Gallate Improves Acne in Humans by Modulating Intracellular Molecular Targets and Inhibiting P. acnes. J
Invest Dermatol 2013;133:429–40.

36. 3. Epigallocatechin-3-Gallate Improves Acne in Humans by Modulating Intracellular Molecular Targets and Inhibiting P. acnes. J
Invest Dermatol 2013;133:429–40.

37. Oral Probiotics
• Treg cells ↓ → inflammatory cytokines ↓
• Sebum production ↓
• Modulate side effects of antibiotics
1. Prospective, Randomized, open-label trial comparing the safety, efficacy and tolerability of an acne treatment regimen with and without a
probiotic supplement and minocycline in subjects with mild to moderate acne. J Cutan Med Surg. 2013 (March/April);17(2).

38. Oral Zinc
• Bacteriostatic effects on P. acnes
• Inflammatory cytokines ↓
• P. acnes resistance to erythromycin ↓
1. Effect of zinc gluconate on propionibacterium acnes resistance to erythromycin in patients with inflammatory acne: in vitro and in vivo study.
Eur J Dermatol. 2005 May–Jun;15(3):152–5.1. Effect of zinc gluconate on propionibacterium acnes resistance to erythromycin in patients with inflammatory acne: in vitro and in vivo study.
Eur J Dermatol. 2005 May–Jun;15(3):152–5.

39. 4. An observational study of methionine-bound zinc with antioxidants for mild to moderate acne vulgaris. Dermatol Ther.
2010;23:411–8.

40. Also consider…
Handbook of Integrative Dermatology: An Evidence-Based Approach

42. Raspberry Ketone
• Insulin-like growth factor ↑ → hair growth
1. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-1 in mice and on hair growth and skin
elasticity in humans. Growth Horm IGF Res. 2008 Aug;18(4):335–44.

43. Procyanidins
• Mechanism of action: unknown
1 . T h e first clinical trial of topical application of procyanidin B-2 to investigate its potential as a hair growing agent. Phytother Res.
2001;15(4):331–6.
2. Investigation of the topical application of procyanidin oligomers from apples to identify their potential use as a hairgrowing agent. J Cosmet

44. Handbook of Integrative Dermatology: An Evidence-Based Approach

46. Topical Vitamin C
• Chelation of copper ions → pigment synthesis
↓
• Improvement:
– 5% ascorbic acid: 62.5%
– 4% HQ: 93%
1. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int J Dermatol. 2004 Aug;43(8):604–7.
2. 2. A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melasma. Dermatology. 2003;206(4):316–20.

47. 2. A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melasma. Dermatology. 2003;206(4):316–
20.

48. Vitamin C Hydroquinone
1. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int J Dermatol. 2004 Aug;43(8):604–7.

49. Oral/Topical Soy
• Melanosome transfer ↓ → dyspigmentation ↓
1. Efficacy of a soy moisturizer in photoaging: adouble-blind, vehicle-controlled, 12-week study. J Drugs Dermatol. 2007;6(9):917–22.

50. Oral/Topical Niacinamide
• Melanosome transfer ↓
• Improvement:
– 4% niacinamide: 44%
– 4% HQ: 55%
– MMP ↓
1. A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone 4% in the treatment of melasma. Dermatol Res Pract.
2011;2011:379173.
2. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol. 2002;147(1):20–31.

51. Niacinamide 4% Hydroquinone 4%
1. A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone 4% in the treatment of melasma. Dermatol
Res Pract. 2011;2011:379173.

52. 3. The effects of a daily facial lotion containing vitamins B3 and E and provitamin B5 on the facial skin of Indian women: a
randomized, double-blind trial. Indian J Dermatol Venereol Leprol. 2010 Jan–Feb;76(1):20–6.

53. Topical Licorice
• Tyrosinase inhibition → melanin production ↓
• Improvement:
– 4% liquiritin: 96.7%
– 4% hydroquinone (HQ) → 73.3%
1. Comparison of efficacy of topical 2% liquiritin, topical 4% liquiritin and topical 4% hydroquinone in the management of melasma. J Pak Assoc
Dermatol 2009;19:158–63.
2. Topical liquiritn improves melasma. Int J Dermatol. 2000;39(4):299–301.

54. Handbook of Integrative Dermatology: An Evidence-Based Approach

56. Case 1
• 15 yo male, well-controlled moderate acne
• Antibiotics 1x1 for 6 months, BPO, topical
retinoid
• Interested in stopping oral antibiotic

57. Case 1
• Excessive dairy intake?
• Abundance of sugar or carbohydrate- rich
foods?
• 500 mg of niacinamide 2x1
• Follow up: consider addition of oral zinc

58. Case 2
• 34 yo female, mild acne
• Well controlled with topical retinoid
• Plans to start pregnancy
• Wants to stop retinoid

59. Case 2
• Balanced diet
• Probiotic juices & yogurt
• Vitamin C serums at night
• Niacinamide during the day
• Topical azelaic acid?

60. Case 3
• 42 yo woman, melasma & solar lentigines
• Hydroquinone for several months, mild
improvement
• Concerned about the side effects
• Not interested in chemical peels or intense
pulsed light therapy

61. Case 3
• Strict photoprotection
• Topical vitamin C preparation 2x1
• Topical licorice

62. Case 4
• 39 yo female, looks “tired”, more lentigines,
redness & overall dullness of her complexion.
• Intolerance to retinoids and AHA
• Confused by various OTC products & botanical
ingredients

63. Case 4
• Morning sunscreen containing soy extracts for
dyspigmentation
• Evening serum containing green tea
polyphenols & topical niacinamide for redness
& dyspigmentation
• Topical vitamin C 2x1 to increase collagenesis
• Diet rich in flavonoids (eg. dark chocolate) &
carotenoids (eg. tomatoes)

64. Benefit >
risk?
Mostly small
samples
Warrants
further
research!
Integrative
Dermatology