> Integrative Dermatology

Natural Ingredients and How to Use Them in Practice – Part 2


Welcome back to our continued discussion on the natural, botanical ingredients that are formulated into skin care products that you can easily incorporate into your practice.

And, in case you missed Part 1, you can read it here.

Mushroom Extract

Mushroom extract, in particular shitake and reishi, retain anti-inflammatory and antioxidant properties. These properties are due to the polysaccharides, cerebrosides, proteins, triterpenes, phenols, and lipids5. Cerebrosides are composed of ceramides, which contribute to the lipid composition of skin and prevent transepidermal water loss. Total phenols identified in medicinal mushrooms promote free radical scavenging and chelating processes6.

Furthermore, increased levels of superoxide dismutase and catalase activity were found in murine skin models after application of mushroom extract compared to controls7. Superoxide dismutase and catalase are important enzymes in the breakdown of free radicals.

Beyond anti-aging, mushroom extract also has been optimized by generations of Eastern medicine for its pigment reduction properties. Reishi mushroom extract inhibits tyrosinase, the melanin-generating enzyme used in topical skin lightening preparations8. Mushroom extract is also capable of inhibiting the enzyme elastase, thereby preserving elastin and structural support of the skin5. The combination of pigment modification and ROS protection makes mushroom extract an effective natural anti-aging therapy. For patients who are looking for an anti-aging natural ingredient that also has skin lightening properties (e.g., patients with melasma, lentigos or post-inflammatory hyperpigmentation), a night cream with mushroom extract would be a nice adjunct to their skin care regimen.


Feverfew (Tanacetum parthenium), as its name entails, was once used as a natural antipyretic. As a result, feverfew’s anti-inflammatory, anti-irritant, and antioxidant qualities have been successful optimized by natural skin products.

As a powerful antioxidant, feverfew has 5 times the capacity of vitamin C (ascorbic acid) to scavenge oxygen and hydroxyl radicals and 13 times the superoxide dismutase activity9. This evidence was substantiated in a randomized placebo-controlled trial where women were asked to apply PD-Feverfew 1% to the skin for two days prior to UV radiation and then reapply for two days after UV exposure. Those with feverfew protection had reported statistically significant reduction in erythema (p<0.05)9.

It is important to advise patients to seek “parthenolide-free” feverfew (i.e., Feverfew PFETM), as parthenolide can cause skin sensitivity and irritation. Cleansers or moisturizers with feverfew are ideal of patients who have sensitive skin and suffer from erythema, such as patients who have rosacea.


Research surrounding niacinamide, the active form of B3, has contributed significantly to the management of many dermatoses. Niacinamide promotes epidermal differentiation, dermal proliferation, and maintains barrier integrity by upregulating epidermal sphingolipids (e.g., ceramides), collagen, and proteins. Loss of these components sacrifices barrier protection and leads to transepidermal water loss, as reported in such conditions as atopic dermatitis and xerosis.

On a biochemical level, aged skin fibroblasts possess higher levels of NAD+ and NADP+, however application of niacinamide converts these cations to endogenous antioxidants NADH and NADPH, restoring homeostasis and driving cell metabolism.

Niacinamide also addresses hyperpigmentation by modifying melanosome deposition in keratinocytes. This process, though currently undefined, is not via tyrosinase inhibition. Niacinamide’s melanin modification is, however, confirmed in an in vivo split-face, vehicle-controlled experiment where hyperpigmentation was significantly reduced with a 5% topical niacinamide application10. It is of note that evidence points toward rebound pigmentation after cessation of niacinamide application.

Lastly, niacinamide treatment significantly improved collagen and protein production by 54% compared to control in in vitro studies11. This data indicates the beneficial effects of niacinamide in recovery of photo-damaged skin and elasticity via collagen restoration.

As it is a form of vitamin B and is found in a number of foods, niacinamide is considered by many patients to be a nice alternative to prescription medications. Many patients who desire to benefit from the anti-aging properties of a retinoid but cannot tolerate this class of ingredients are pleasantly surprised to learn that niacinamide has many of the same benefits and is very well tolerated.


Soy contains two main ingredients, phytosterols and small serine protease inhibitors (SSPIs). Bowman-Birk inhibitor and soybean trypsin inhibitor are two examples of soy-specific SSPIs. Phytosterols act as antioxidants while SSPIs act on protease-activated receptor-2 pathway, leading to skin pigmentation reduction.

Similar to niacinamide, in vitro studies have shown collagen production promotion5. Larger randomized controlled trials and cohort studies have examined the role of soy in multiple other parameters of skin improvement. A vehicle-controlled, parallel, randomized trial of 65 women with moderate sun damage was conducted to evaluate the efficacy of topical soy. After 12 weeks of therapy, reduction in uneven pigment, fine lines, texture smoothness, redness and dullness was observed12.

Soy has phytoestrogens, primarily isoflavones genistein and daidzein. Genistein and daidzein are present in topical preparations as glycosides without any estrogenic effect, unless converted to their free isoflavone state. Regardless, these phytoestrogens, though similar to estradiol, have only weak estrogenic effect and consequently some concern exists regarding an increased risk of breast or uterine cancer. Data addressing this concern has been controversial and inconclusive. Although the phytoestrogens in soy could theoretically promote cancer cell growth, epidemiological data suggest a protective effect of soy against breast cancer development (possibly due to its antioxidant activity). At present, research is insufficient to determine the long-term estrogenic effects of topical soy.13 In the opinion of the authors, patients with acne breast cancer should avoid the use of topical soy.


The continued interest in natural ingredient combined with the enduring pursuit for the “fountain of youth” has generated significant investigation into alternative organic therapies. Products that include green tea, mushroom extract, feverfew, niacinamide and soy are viable options supported by evidence-based medicine. In vitro and in vivo animal and human models confirm their antioxidant, anti-inflammatory, and epidermal modification properties. These treatments are also valuable due to their safety profiles and limited contact hypersensitivity. Though they may not replace pharmaceutical options, they are viable, easily accessible first-line or adjunctive therapies.

There are few controlled clinical trials looking at penetration or optimal substrate concentrations, as well as a lack of regulation of the term “organic.” These parameters should continue to be investigated and additional large-scale randomized controlled human trials would contribute significantly to the realm of organic therapies.

As a dermatologist, you are considered an expert in all things skin-related. As such, your patients will frequently seek your guidance when it comes to purchasing over-the-counter products. Natural and naturally-derived ingredients continue to take up more and more shelf space as consumers show continued interest in this product category. It is critical that you have a working knowledge of at least a handful of natural ingredients that demonstrate efficacy and safety, so that you can maintain credibility with your patients while helping them address their skin care concerns. For holistic dermatology, check out our series.


  • ROS – Reactive oxygen species
  • GTPs – Green tea polyphenols
  • SOD – Superoxide dismutase
  • SSPIs – Small serine protease inhibitors

References and Suggested Readings

  • 5. Berson, D. S. (2008). “Natural antioxidants.” J Drugs Dermatol 7(7 Suppl): s7-12.
  • 6. Mau, J. L., et al. (2002). “Antioxidant properties of several medicinal mushrooms.” J Agric Food Chem 50(21): 6072-6077.
  • 7. Cherian, E., et al. (2009). “Free-radical scavenging and mitochondrial antioxidant activities of Reishi-Ganoderma lucidum (Curt: Fr) P. Karst and Arogyapacha-Trichopus zeylanicus Gaertn extracts.” J Basic Clin Physiol Pharmacol 20(4): 289-307.
  • 8. Chien, C. C., et al. (2008). “Effects on tyrosinase activity by the extracts of Ganoderma lucidum and related mushrooms.” Mycopathologia 166(2): 117-120.
  • 9. Martin, K., et al. (2008). “Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV irradiation and external aggression.” Arch Dermatol Res 300(2): 69-80.
  • 10. Boissy RE, Minwalla L, Bissett DL, Zhuang JC, Chhoa M. Niacinamide inhibits transfer of melanosomes from melanocytes to keratinocytes. 59th Annual Meeting American Academy of Dermatology, Washington, 2001.
  • 11. Oblong JE, Bissett DL, Ritter JL, Kurtz KK, Schnicker MS. Niacinamide stimulates collagen synthesis from human dermal fibroblasts and differentiation marker in normal human epidermal keratinocytes: potential of niacinamide to normalize aged skin cells to correct homeostatic balance. 59th Annual Meeting American Academy of Dermatology, Washington, 2001.
  • 12. Wallo, W., et al. (2007). “Efficacy of a soy moisturizer in photoaging: a double-blind, vehicle-controlled, 12-week study.” J Drugs Dermatol 6(9): 917-922.
  • 13. Levin J, Momin SB. (2010). “How much do we really know about our favorite cosmeceutical ingredients?” J Clin Aesthet Dermatol 3(2):22-41.

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