329 Topical Apple Derivatives
chemical burns after his mother placed cotton balls with apple cider vinegar over the lesions
for approximately 8 hours.19 While stronger acids are more likely to cause chemical burns,
this case is unique in that a weak acid derived from apples resulted in the chemical burns.19
APPLE CAN ATTENUATE CHEMOTHERAPY-INDUCED ALOPECIA
One experimental study tested the effectiveness of an industrial polycyanidic extract
of Annurca apple (AnnurtriComplex® 6% foam (Mb Med., Turin, Italy) for treating
chemotherapy-induced alopecia in mice (Table II). The study found that the apple extract
enhances mitochondrial activity in hair follicles, resulting in changes in signaling molecules
in the hair follicles. Treated hair follicles damaged by chemotherapy contained structural
and molecular similarities to hair follicles undamaged by chemotherapy. It was found that
inactivating alterations of prostanoid PGF2α is likely the main contributor in the hair
promoting effects of this cosmetic foam.20
APPLE CIDER VINEGAR IS NOT EFFECTIVE IN TREATING ATOPIC DERMATITIS
A controlled clinical trial tested the therapeutic potential of apple cider vinegar in
improving the skin barrier integrity in atopic dermatitis (Table I). Daily topical 0.5%
apple cider vinegar soaks found no long-term effects on skin TEWL or skin pH.21 The
soaks were effective in reducing skin pH, but this effect was not sustained at 60 minutes
post-treatment. 73% of subjects with atopic dermatitis reported mild skin discomfort of
the forearm soaked in apple cider vinegar. One subject with atopic dermatitis experienced
severe pruritus, erosion, and burning of the soaked forearm, which resolved within two days
of discontinuing apple cider vinegar soaks. One healthy subject experienced a nonpruritic
papular rash which resolved without any treatment.21
Another controlled clinical trial tested the potential of apple cider vinegar to alter the skin
microbiome in atopic dermatitis on human subjects (Table II). Daily topical 0.5% apple
cider vinegar soaks were ineffective in altering the skin microbiome or the abundance of
Staphylococcus aureus after two weeks.1
APPLE EXTRACTS CAN CAUSE URTICARIA AND DERMATITIS
The second case report that was reviewed involved a 16-year-old male with atopy. The
topical application of apple, carrot, and potato extracts resulted in contact urticaria
periorally on both hands and on the nape.22 Removal of the extracts cleared any urticaria
and dermatitis.22
DISCUSSION
According to the current evidence, apple derivatives were found to be effective in treating
some dermatological diseases. The strongest evidence was found for treatment of male
pattern baldness, which has 4 double-blind clinical trials with more than more than 20
subjects in each treatment group, 3 of which were tested in human males, and one tested in
mice. Male pattern baldness, the most common cause of hair loss in men, is a multifactorial

330 JOURNAL OF COSMETIC SCIENCE
condition defined by a progressive thinning of hair in a specific pattern that can often be
seen as a receding hairline.23 Procyanidins, like those found in apples, have been found to
have growth-promoting effects on murine hair cells.24 Three of the four reviewed studies
looked at how procyanidins could affect the growth of human hair cells and, by relation,
could possibly treat male pattern baldness. The results of the studies showed an increased
growth in the number of hairs and hair density with no adverse effects when procyanidin
was used.5,15,25 This suggests that procyanidin oligomers have growth-promoting effects
on human hair cells and could therefore be used as a safe and effective treatment for male
pattern baldness. The fourth study investigated the mechanism of growth-promoting
effects of procyanidin B2 on hair follicles in mice. The study used Annurca polyphenolic
extract the Annurca apple species contains one of the highest contents of procyanidin B2.4
The study found that mice hair follicles treated with Annurca polyphenolic acid underwent
metabolic reprogramming, which increased rates of β-oxidation and increased overall
mitochondrial activity in comparison to those treated with placebo. This study was able
to replicate growth-promoting effects with procyanidin B2 in mice and was further able
to prove a mechanism behind those growth-promoting effects. Knowing how procyanidin
B2 alters hair follicles, this pathway can be further extrapolated to create more effective
treatment options for patients with male pattern hair loss. However, it is uncertain that
effects in human hair follicles are the same as those observed in mice hair follicles, therefore
further studies in human hair follicles are indicated.4
Antioxidant and cosmetic effects of apple derivatives are also supported by evidence that
still needs further development in human subjects through long-term study. UV radiation
plays a significant role in skin aging, especially photoaging, through skin damage that
results from the generation of reactive oxygen species, oxidative damage, and eventual DNA
fragmentation in skin cells.26 Many products have been investigated to determine their
efficacy in dampening the features of skin aging. Research has shown that apple derivatives
play a promising role in reducing the damaging effects that UV radiation exposure has
on the skin. One study by Shin et al. revealed that a serum medium containing 1%
phloretin 3’,3-disulfonate, a modified phloretin derived from apple, significantly decreased
UVB-mediated DNA damage, UVB-mediated apoptosis, and UVB-induced cell growth
inhibition in HaCaT keratinocytes. The mechanism that explains this finding is suspected
to involve the upregulation of XPA and XPC genes, which play a major role in nucleotide
excision repair after DNA damage.17 Moreover, the study revealed that treatment with
phloretin 3’,3-disulfonate post-UVB irradiation resulted in an increase in GSH levels and
a significant decrease in COX-2 expression. GSH is an endogenous tripeptide that plays a
major role in scavenging free radicals to protect cells from oxidative damage. The increase
in GSH in the UV-irradiated HaCaT keratinocytes suggests that phloretin 3’,3-disulfonate
may participate in the modulation of cellular redox signaling and cell death activation
by preserving the GSH levels within the cells.17 Furthermore, COX-2 is an important
enzyme that produces pro-inflammatory mediators in response to attacks on the body.
The reduction in COX-2 expression in UV-irradiated HaCaT keratinocytes indicates that
phloretin 3’,3-disulfonate may have an effect on the inflammatory pathway, reducing
the potential for further damage from prolonged intracellular exposure to inflammatory
mediators.17
A human clinical study also performed by Shin et al. demonstrated that treatment with 0.05%
phloretin 3’,3-disulfonate gel significantly reduced UV-induced skin erythema after 6 days.
Phloretin 3’3-disulfonate is known to have antioxidant and anti-inflammatory properties (as