Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study

Skin lesions such as acne affect a large portion of the population. Teenagers between the ages of 13 and 18 typically experience the highest rates, affecting approximately 80% of individuals. (18)

Some studies cite the prevalence in adolescents as high as 85%. (23) Additionally, skin lesions continue to affect 3% of men and 12% of women over 25 years of age. (18

Addressing the possible underlying mechanisms involved in the development of skin lesions is vital to an integrative treatment plan. Certain topical and dietary supplement therapies show promising results. For example, decreasing sebum production may play a role in improving total lesion count. (4)(23) Other interventions suggest that inducing anti-inflammatory mechanisms via the suppression of NF-κB and AP-1 pathways may subsequently decrease the number of inflammatory lesions. (23)

Based on the research findings, the ingredients presented in the protocol below have demonstrated efficacy in alleviating skin lesions such as comedones, inflammatory papules, and pustules.

Zinc gluconate

30 mg elemental zinc from zinc gluconate (preferably, although other forms may be effective), once per day, 6-12 weeks (7)

  • A decrease in inflammatory score demonstrated by the number of inflammatory lesions was observed in individuals receiving zinc gluconate supplementation when compared to placebo (4)(6)(7) 
  • Compared to baseline, zinc sulfate supplementation resulted in a decreased number of papules, pustules, infiltrates, and cysts in 58% of patients (16)(21)
  • Overall improvement in lesion counts following zinc sulfate supplementation when compared to placebo, with improved efficacy over the duration of 12 weeks (10)(15
  • Systematic review and meta-analysis found zinc relieved symptoms of acne by decreasing the number of inflammatory papules (22)
  • Systematic review found both topical and oral zinc to be effective for acne treatment, potentially due to antibacterial, anti-inflammatory, and decreased sebum production (4)
  • Zinc was inferior to minocycline however still resulted in 31.2% clinical success rate in the treatment of inflammatory acne (7)
Zinc gluconate in the Fullscript catalog

Tea tree oil (Melaleuca alternifolia)

5% tea tree oil gel applied topically, 1-2 times per day, 45 days to 12 weeks (2)(8)(13

Note: It is suggested to dilute tea tree essential oil with a carrier oil (e.g., olive oil) to avoid skin irritation (3

  • Application of tea tree oil gel decreased total number of inflamed and non-inflamed acne lesions, being 3.55 times more effective than placebo on total acne lesion count and 5.75 times more effective than placebo on acne severity index (8
  • Decreased number of open and closed comedones for inflamed and non-inflamed lesions when treated with tea tree oil of benzoyl peroxide; fewer side effects observed in those treated with tea tree oil gel when compared with benzoyl peroxide lotion (2)
  • Tea tree oil gel and face wash used twice daily was found to improve acne via a decrease in mean total lesion count and mean investigator global assessment score (13)
Tea tree oil in the Fullscript catalog

Green tea extract (Camellia sinensis)

1500 mg green tea extract (with standardized EGCG of 856 mg), once per day, minimum 4 weeks; (12) or 1-5% tea catechin gel, applied topically 1-2 times per day, minimum 8 weeks (19)(23)

  • Decreased revised Leeds score, which assesses inflammatory and noninflammatory acne lesions such as papules, pustules, nodules, cysts, and comedones, following topical application of both 1% and 5% EGCG; EGCG regulated the AMPK-SREBP-1 signaling pathway, inhibited NF-κB and AP-1 signaling pathways and caused cytotoxicity of SEB-1 sebocytes, thereby reducing inflammation, sebum production and P. acnes (23
  • Lesion count of acne vulgaris decreased with 2% green tea topical lotion application compared to baseline and placebo (19
  • Oral supplementation (856 mg EGCG per day, 4 weeks) reduced number of facial inflammatory lesions on the nose, perioral area, and chin, when compared to baseline in women with post-adolescent acne (12)
  • Systematic review and meta-analysis of five randomized controlled studies found topical green tea extract improved acne by decreasing number of inflammatory lesions (11)
Green tea extract in the Fullscript catalog

Turmeric (Curcuma longa)

As directed, dosing varies greatly (1)(14)(20

  • Systematic review of 18 studies found both oral and topical turmeric preparations to be effective in alleviating skin conditions such acne, atopic dermatitis, pruritus, and psoriasis compared to control (20)
  • Systematic review of 11 studies found turmeric supplementation to show benefit in patients with skin conditions such as psoriasis, pruritus, and facial redness (14)
  • Systematic review of 12 studies found Curcuma longa and Curcuma aeruginosa to aid in decreasing inflammation and improve skin conditions such as radio-dermatitis (1)
Turmeric in the Fullscript catalog

Lactoferrin

As directed, minimum of 8 weeks (5)(17)

  • Reduced inflammatory lesions by 20.2% and non-inflammatory lesions by 23.5% compared to baseline in patients with mild to moderate facial acne (17)
  • Systematic review of six studies found lactoferrin may alleviate acne, psoriasis, and diabetic ulcerations (9)
  • Decreased total lesion count compared to placebo in patients with mild to moderate acne (5)
Lactoferrin in the Fullscript catalog

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

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References
  1. Barbalho, S. M., de Sousa Gonzaga, H. F., de Souza, G. A., de Alvares Goulart, R., de Sousa Gonzaga, M. L., & de Alvarez Rezende, B. (2021). Dermatological effects of Curcuma species: a systematic review. Clinical and Experimental Dermatology https://pubmed.ncbi.nlm.nih.gov/33522006/ (A)
  2. Bassett, I. B., Pannowitz, D. L., & Barnetson, R. S. (1990). A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. The Medical Journal of Australia, 153(8), 455–458. https://pubmed.ncbi.nlm.nih.gov/2145499/ (C)
  3. Boehm, K., Büssing, A., & Ostermann, T. (2012). Aromatherapy as an adjuvant treatment in cancer care–a descriptive systematic review. African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM / African Networks on Ethnomedicines, 9(4), 503–518. https://pubmed.ncbi.nlm.nih.gov/23983386/ (A)
  4. Brandt, S. (2013). The clinical effects of zinc as a topical or oral agent on the clinical response and pathophysiologic mechanisms of acne: a systematic review of the literature. Journal of Drugs in Dermatology: JDD, 12(5), 542–545. https://pubmed.ncbi.nlm.nih.gov/23652948/ (A)
  5. Chan, H., Chan, G., Santos, J., Dee, K., & Co, J. K. (2017). A randomized, double-blind, placebo-controlled trial to determine the efficacy and safety of lactoferrin with vitamin E and zinc as an oral therapy for mild to moderate acne vulgaris. International Journal of Dermatology, 56(6), 686–690. https://pubmed.ncbi.nlm.nih.gov/28369875/ (B)
  6. Dreno, B., Amblard, P., Agache, P., Sirot, S., & Litoux, P. (1989). Low doses of zinc gluconate for inflammatory acne. Acta Dermato-Venereologica, 69(6), 541–543. https://pubmed.ncbi.nlm.nih.gov/2575335/ (C)
  7. Dreno, B., Moyse, D., Alirezai, M., Amblard, P., Auffret, N., Beylot, C., Bodokh, I., Chivot, M., Daniel, F., Humbert, P., Meynadier, J., Poli, F., & Acne Research and Study Group. (2001). Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment of inflammatory acne vulgaris. Dermatology , 203(2), 135–140. https://pubmed.ncbi.nlm.nih.gov/11586012/ (C)
  8. Enshaieh, S., Jooya, A., Siadat, A. H., & Iraji, F. (2007). The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: a randomized, double-blind placebo-controlled study. Indian Journal of Dermatology, Venereology and Leprology, 73(1), 22–25. https://pubmed.ncbi.nlm.nih.gov/17314442/ (B)
  9. Hassoun, L. A., & Sivamani, R. K. (2017). A systematic review of lactoferrin use in dermatology. Critical Reviews in Food Science and Nutrition, 57(17), 3632–3639. https://pubmed.ncbi.nlm.nih.gov/26857697/ (A)
  10. Hillström, L., Pettersson, L., Hellbe, L., Kjellin, A., Leczinsky, C. G., & Nordwall, C. (1977). Comparison of oral treatment with zinc sulphate and placebo in acne vulgaris. The British Journal of Dermatology, 97(6), 681–684. https://pubmed.ncbi.nlm.nih.gov/146511/ (B)
  11. Kim, S., Park, T. H., Kim, W. I., Park, S., Kim, J. H., & Cho, M. K. (2021). The effects of green tea on acne vulgaris: A systematic review and meta-analysis of randomized clinical trials. Phytotherapy Research: PTR, 35(1), 374–383. https://pubmed.ncbi.nlm.nih.gov/32812270/ (A)
  12. Lu, P. H., & Hsu, C. H. (2016). Does supplementation with green tea extract improve acne in post-adolescent women? A randomized, double-blind, and placebo-controlled clinical trial. Complementary Therapies in Medicine, 25, 159–163. https://pubmed.ncbi.nlm.nih.gov/27062963/ (B)
  13. Malhi, H. K., Tu, J., Riley, T. V., Kumarasinghe, S. P., & Hammer, K. A. (2017). Tea tree oil gel for mild to moderate acne; a 12 week uncontrolled, open-label phase II pilot study. The Australasian Journal of Dermatology, 58(3), 205–210.
    1. https://pubmed.ncbi.nlm.nih.gov/27000386/ (C)
  14. Mata, I. R. da, Mata, S. R. da, Menezes, R. C. R., Faccioli, L. S., Bandeira, K. K., & Bosco, S. M. D. (2020). Benefits of turmeric supplementation for skin health in chronic diseases: a systematic review. Critical Reviews in Food Science and Nutrition, 1–15. https://pubmed.ncbi.nlm.nih.gov/32713186/ (A)
  15. Michaëlsson, G., Juhlin, L., & Ljunghall, K. (1977). A double-blind study of the effect of zinc and oxytetracycline in acne vulgaris. The British Journal of Dermatology, 97(5), 561–566. https://pubmed.ncbi.nlm.nih.gov/145237/ (C)
  16. Michaëlsson, G., Juhlin, L., & Vahlquist, A. (1977). Effects of oral zinc and vitamin A in acne. Archives of Dermatology, 113(1), 31–36. https://pubmed.ncbi.nlm.nih.gov/137693/ (C)
  17. Mueller, E. A., Trapp, S., Frentzel, A., Kirch, W., & Brantl, V. (2011). Efficacy and tolerability of oral lactoferrin supplementation in mild to moderate acne vulgaris: an exploratory study. Current Medical Research and Opinion, 27(4), 793–797. https://pubmed.ncbi.nlm.nih.gov/21303195/ (C)
  18. Purdy, S., & de Berker, D. (2011). Acne vulgaris. BMJ Clinical Evidence, 2011. https://pubmed.ncbi.nlm.nih.gov/21477388/ (A)
  19. Sharquie, K. E., Al-Turfi, I. A., & Al-Shimary, W. M. (2006). Treatment of acne vulgaris with 2% topical tea lotion. Saudi Medical Journal, 27(1), 83–85. https://pubmed.ncbi.nlm.nih.gov/16432600/ (C)
  20. Vaughn, A. R., Branum, A., & Sivamani, R. K. (2016). Effects of Turmeric (Curcuma longa) on Skin Health: A Systematic Review of the Clinical Evidence. Phytotherapy Research: PTR, 30(8), 1243–1264. https://pubmed.ncbi.nlm.nih.gov/27213821/ (A)
  21. Verma, K. C., Saini, A. S., & Dhamija, S. K. (1980). Oral zinc sulphate therapy in acne vulgaris: a double-blind trial. Acta Dermato-Venereologica, 60(4), 337–340. https://pubmed.ncbi.nlm.nih.gov/6163281/ (B)
  22. Yee, B. E., Richards, P., Sui, J. Y., & Marsch, A. F. (2020). Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatologic Therapy, 33(6), e14252. https://pubmed.ncbi.nlm.nih.gov/32860489/ (A)
  23. Yoon, J. Y., Kwon, H. H., Min, S. U., Thiboutot, D. M., & Suh, D. H. (2013). Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P. acnes. The Journal of Investigative Dermatology, 133(2), 429–440. https://pubmed.ncbi.nlm.nih.gov/23096708/ (C)