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Sulfur  

OVERVIEW
History and Significance
Applications

CHEMISTRY
General Manufacturing Process
Available Formulations
Biologic Activity
Metabolism
Synthesis
Oxidative Effects

APPROVED INDICATIONS AND THERAPEUTIC USE
Acne
Seborrheic Dermatitis
Rosacea
Eczema, Psoriasis
Pityriasis versicolor
Scabies, Lice

CLINICAL CONSIDERATIONS
Patient Instructions
Duration and Frequency of Treatment
Contraindications, Warnings, Precautions

PRODUCT SELECTION FOR RESULTS

REFERENCES

Sulfur  

 OVERVIEW

Sulfur is a naturally occurring mineral that is found primarily near volcanic craters and hot springs, as well as in the amino acids, cysteine and methionine, which serve as the foundation for polypeptides, proteins and enzymes. The therapeutic properties of sulfur have been recognized by ancient civilizations to treat a variety of ailments. In its native form, sulfur is recognized as a yellow crystalline solid as a pure element (also known as brimstone) and combined as sulfide and sulfate minerals. Sulfur supports metabolic and neural function in combination with vitamins B1 (thiamine), B5 (pantothenic acid) and H (biotin). It is vital to collagen synthesis, evidenced by its abundance in keratin.1

 History and Significance

Sulfur is found primarily in volcanic ash and hot springs, which are located near the Pacific "Ring of Fire", eastern Europe, western Asia, and along the coast of the Gulf of Mexico. These resources enabled ancient civilizations to recognize the therapeutic benefits of balneotherapy (in sulfur springs or mud baths) for pain, and the abundance of sulfur has been included in ancient texts and traditional Chinese medicine. In 1990, the FDA banned 27 ingredients used in dandruff shampoos; sulfur was one of only five ingredients approved for nonprescription use.2 Sulfur is approved by the FDA as an active ingredient in over-the-counter (OTC) medications for acne, dandruff, seborrheic dermatitis, and psoriasis3. Additional clinical data is being evaluated for OTC use as an active ingredient for anorectal, antifungal, pediculicide, and skin protectant applications.3 Scientific literature on clinical studies and the clinical application of topical sulfur formulations is vast.

 Applications

The abundance of sulfur and its related compounds have a broad span of applications, including manufacturing (gunpowder, rubber, cellophane, and polymers), chemistry (sulfuric acid), agriculture (fertilizers), and healthcare. Methylsulfonylmethane (MSM) is a dietary supplement for joint and connective tissue support. FDA-approved formulations contain the supplement, dimethyl sulfoxide (DMSO). Topical formulations include cleansers, creams, and ointments.4,5 The properties of sulfur, its role in biologic processes, and its versatility in compounds provide healthcare professionals with options to optimize each patient's dermatologic treatment strategy.6

 CHEMISTRY

Chemical name: sulfur (also known as colloidal sulfur or precipitated sulfur)



 General Manufacturing Process

Elemental sulfur is commercially extracted from hydrogen sulfide present in petroleum and natural gas using what is commonly known as the Claus process. For biologic use, hydrogen sulfide is combined with a slight alkaline solution in a wet scrubber to produce a biosulfur product that is hydrophilic.

 Available Formulations

Sulfur is an active ingredient found in lotions, creams, gels, washes, and shampoos. KAVI manufactures dermatologic formulations containing colloidal sulfur, which efficiently provides the same potency as suspended sulfur particles, but at a fraction of the concentration, thereby reducing the level of irritation and minimizing the associated smell from sulfur's oxidative process. Sulfur and sulfur compounds are widely available combined with other agents.

 Biologic Activity

Sulfur plays an important role in metabolism and synthesis, as part of the amino acids that comprise polypeptides, proteins, and enzymes. In addition to its role as a supplement, sulfur produces a mild oxidative effect when used as a topical application.

 Metabolism

The amino acids cysteine and methionine contain sulfur and are the foundation for polypeptides, proteins, and enzymes. Other biologic components containing sulfur include homocysteine, taurine, and glutathione, all essential as antioxidants and in tissue regulation. Cellular enzymes and peptides that contain a sulfydryl (-SH) moiety facilitate reactions involving acyl-containing compounds such as coenzyme A and alpha-lipoic acid. Catabolism, the converse of metabolism, can be induced with sulfur and added compounds (such as hydrogen sulfide) for desulfurization.

 Synthesis

Protein assembly and structure relies on the formation of disulfide bonds (S-S bonds) between cysteine residues in peptide chains. Stable covalent bonds between peptide chains provide proteins with their unique strength and resiliency. Clear examples of these bonds are feathers and eggs, which contain large concentrations of protein and sulfur. Birds' eggs contain large amounts of sulfur for protein synthesis. The high disulfide content of hair and feathers contributes to their indigestibility and also their odor when burned.

 Oxidative Effects

Elemental sulfur oxidizes slowly to sulfurous acid in the presence of water, which as a sulfite, has an antibacterial and mild reducing effect.

 APPROVED INDICATIONS AND THERAPEUTIC USE

APPROVED INDICATIONS
Acne
Seborrheic Dermatitis
Rosacea
Eczema, Psoriasis
Pityriasis versicolor
Scabies, Lice
 Acne

Sulfur-containing formulations have proven effectiveness as a micro-exfoliant and mild antiseptic through its oxidative properties in topical applications. Biologic formulations of sulfur are hydrophilic, enabling dermal penetration to promote collagen and protein synthesis while reducing bacterial infections associated with breakouts. Propionibacterium acnes is a normal inhabitant of sebaceous follicles and a healthy population is maintained by cysteine. Abnormal proliferation of P. acnes alters the skin's pH, effecting acne infection. Clinical studies have demonstrated that sulfur formulations such as those containing sodium sulfite inhibit the growth of P. acnes by desulfurization of cysteine with the concomitant formation of hydrogen sulfide (cysteine catabolism).7 Topical application of sulfur enables penetration into sebaceous pores to the keratogenous zone for metabolic and catabolic availability. Mild oxidative effects of topical sulfur enhance treatment of infection through its antibacterial action and helps restore normal pH. Sulfur is included in combination therapy to enhance the penetration of other agents, such as salicylic acid.8 Over-the-counter formulations contain up to a 2% concentration of colloidal sulfur or a 10% concentration of precipitated sulfur.

 Seborrheic Dermatitis

Sulfur is one of five ingredients that are approved by the FDA as an active ingredient to treat seborrheic dermatitis. Biologic formulations of sulfur enable penetration to dermal layers to optimize micro-exfoliation. The mild oxidative effect of sulfur neutralizes the effects of yeast normally present in sebaceous skin. The oxidative properties and metabolic significance of sulfur has been extensively studied, and systemic absorption of the topical agent is minimal to moderate.2,3

 Rosacea

Rosacea is a chronic, relapsing skin disorder characterized by facial flushing, persistent erythema, telangiectasia, and inflammatory papules and pustules affecting the central face.9,10 Patients can exhibit several subtypes of rosacea, and cosmesis is a significant factor in determining treatment. Topical applications of sulfur, such as sodium sulfacetamide and OTC sulfur formulations, have been shown to be effective in monotherapy and adjunctive care, providing patients with clinically significant improvements in severity with favorable safety and tolerability profiles and enhanced quality of life.11,12

 Eczema, Psoriasis

Chronic eczema and psoriasis can present red, scaly skin rashes. Diagnosis for each disease can be differentiated according to location: eczema-prone areas are flexor surfaces and psoriasis-prone areas are extensor surfaces. The severity of psoriasis is based on the extent of the condition (percentage of body affected) and its level of impact on a patient's life.13 Topical sulfur assists in promoting desquamation of the epidermis and collagen synthesis, preparing the skin for absorption of topical medication. The histology of psoriatic epidermis has been studied to detect an abnormal pattern of keratinocyte differentiation14, which supports the effectiveness of topical sulfur applications for its properties in oxidation, metabolism, and synthesis.

 Pityriasis versicolor

Pityriasis versicolor is a skin condition that presents as flaky discolorations on the trunk, neck, and arms. It is common in hot, humid climates and among patients with hyperhidrosis. Pityriasis versicolor is caused by yeasts present in normal skin which affect pigment function. Sulfur compounds are used to treat the active condition to oxidize the epidermis and enhance antiseptic effects with a combination formulation. Sulfur supports biosynthesis of protein present in pigmented cells for normalized function.

 Scabies, Lice

Sulfur as a component of amino acids acts as a regulatory signal during immune responses to parasitic challenges.15 Infestations have been historically treated with balneotherapy, and ointments containing sulfur applied to dry lesions, descale skin and excavate the organisms. Clinical studies support the therapeutic effectiveness of topical sulfur applications to resolve the majority of cases for human scabies (95% in one study16), thereby providing a safer alternative for children, pregnant women and the elderly, where there is concern for potential toxicity.16

 CLINICAL CONSIDERATIONS
 Patient Instructions; Duration and Frequency of Treatment

KAVI cleansing bars, liquid cleansers, and anti-acne treatments can be used frequently and daily as instructed.

Cleansing Bars: Regular, daily use is recommended. pH-balancing properties favor replacement of other cleansers with KAVI sulfur-based cleansers for long-term use.
DermaWash, Shampoo: Daily use is recommended.
Complex P: Apply a thin layer to acne lesions once or twice per day after cleansing to repair infected pores.
Organic Sulfur Suspension: Apply to skin one to two times per day after cleansing with DermaWash, Aqua KAVI, or Coral KAVI.
Reduce frequency of application if skin becomes too dry.

 Contraindications, Warnings, Precautions

For external use. Do not use on irritated or sunburned skin, or on open wounds or sores. Suspend use if excessive dryness and discomfort is observed. KAVI anti-acne sulfur topicals are not intended for use on a regular basis with other oral or topical antiseborrheics.

 PRODUCT SELECTION FOR RESULTS

Sulfur is a versatile and effective ingredient in topical treatments. Healthcare professionals have product options for sulfur formulations to meet the goals of their treatment plan and needs of the patient. Colloidal sulfur provides patients with products that have the same potency as precipitated sulfur, with the added benefits of reduced irritation and odor.

KAVI Products have been developed to provide professionals with a line of high-quality products that can be configured for your treatment needs. The following table provides an overview of available products and their corresponding indications.

AcneRosaceaClogged, Infected, or Inflamed PoresSeborrheic DermatitisEczema, Psoriasis
DermaWash 
Aqua KAVI
Coral KAVI  
Sulfur Shampoo  
Organic Sulfur Suspension   
Complex P   


Additional information on the KAVI 1% liquid sulfur cleanser (equivalent to 5% precipitated sulfur soap)
Additional information on the KAVI 1% sulfur cleansing bar (equivalent to 5% precipitated sulfur soap)
Additional information on the KAVI 2% sulfur cleansing bar with 3% salicylic acid (equivalent to 10% precipitated sulfur soap)
Additional information on the KAVI 0.5% sulfur shampoo
Additional information on the KAVI 6.6% precipitated sulfur suspension
Additional information on the KAVI 2% sulfur, 5% benzoyl peroxide cream

 REFERENCES

1. Ehrlich SD. "Sulfur", University of Maryland Medical Center, Sep, 2007. Available online. Accessed June 2, 2009.
2. Hingley AT. "OTC Options: Controlling Dandruff", FDA, Oct, 1994 Available online. Accessed June 2, 2009.
3. OTC Ingredient List, FDA, 2008. Available online. Accessed June 2, 2009.
4. Olansky S. "Old Drug in a New System - Revisited", Cutis. Jun, 1977; 19(6):852-4.
5. Gupta AK, Nicol K. "The Use of Sulfur in Dermatology", J Drugs Dermatol. Jul-Aug, 2004; 3(4):427-31.
6. Margolis DJ. "Evidence-Based Dermatology", Cutis. Mar, 2005; 75(3 Suppl):8-12; Discussion 33-6. Review.
7. Nielsen PA. "Role of Reduced Sulfur Compounds in Nutrition of Propionibacterium Acnes", J Clin Microbiol. Feb, 1983; 17(2):276-279.
8. Harlan SL. "Steroid Acne and Rebound Phenomenon", J Drugs Dermatol. Jun, 2008; 7(6):547-50.
9. Gooderham M. "Rosacea and its Topical Management", Skin Therapy Lett. Feb, 2009; 14(2):1-3. Available online.
10. Wilkin J, Dahl M, Detmar M, et al. "Standard Classification of Rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea", J Am Acad Dermatol. 2002; 46:584-7.
11. Trumbore MW, Goldstein JA, Gurge RM. "Treatment of Papulopustular Rosacea with Sodium Sulfacetamide 10% / Sulfur 5% Emollient Foam", J Drugs Dermatol. Mar, 2009; 8(3):299-304.
12. Del Rosso JQ. "Evaluating the Role of Topical Therapies in the Management of Rosacea: Focus on Combination Sodium Sulfacetamide and Sulfur Formulations", Cutis. Jan, 2004; 73(1 Suppl):29-33. Review.
13. "Treating Psoriasis: Mild Psoriasis", National Psoriasis Foundation, Available online. Accessed June 2, 2009.
14. Easty DJ, Patel K, Otto WR, et al. "A Study of Protein Synthesis in Cells Cultured from Involved Psoriatic Skin", Electrophoresis. Jul-Aug, 1991; 12(7-8):579-84.
15. Pain SJ, Revell DK, James PJ. "Effect of Sulphur Amino Acids on Epithelial Immunity and Parasite Susceptibility", Asia Pac J Clin Nutr. 2003; 12 Suppl:S58.
16. Díaz M, Cazorla D, Acosta M. "Efficacy, Safety and Acceptability of Precipitated Sulphur Petrolatum for Topical Treatment of Scabies at the City of Coro", Falcon State, Venezuela Rev Invest Clin. Sep-Oct, 2004; 56(5):615-22.

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