Article 13 November 2020
UCIBIO/REQUIMTE, MedTech, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge de Viterbo 228, 4050-313 Porto, Portugal
Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge de Viterbo 228, 4050-313 Porto, Portugal
Author to whom correspondence should be addressed.
The development of synthetic peptides for skin care dates to the 1980s. The cosmetic industry periodically launches new peptides, as they are promising and appealing active ingredients in the growing and innovative cosmetics market. In this study, trends in the use of peptides in anti-aging products were analyzed by comparing the composition of the products marketed in 2011 with products launched or reformulated in 2018. The scientific and marketing evidence for their application as active ingredients in anti-aging cosmetics was also compiled from products’ labels, suppliers’ technical data forms and online scientific databases. The use of peptides in anti-aging cosmetics increased by 7.2%, while the variety and the number of peptide combinations in products have increased by 88.5%. The most used peptides in antiaging cosmetic formulations are, in descending order, Palmitoyl Tetrapeptide-7, Palmitoyl Oligopeptide and Acetyl Hexapeptide-8. In 2011, the majority of peptides were obtained from synthesis, while in 2018, biotechnology processing was the dominant source. This study provides an overview of the market trends regarding the use of peptides in anti-aging products, providing meaningful data for scientists involved in the development of new peptides to identify opportunities for innovation in this area.
The anti-aging market is expected to grow at an approximate 8% compound annual growth rate between 2018 and 2021, reaching a value of USD 271.0 billion by 2024 [1]. As the competition increases among cosmetic brands from the anti-aging market, new products claim to contain the ultimate innovations in order to stand out, often advertising new active ingredients.
Glutathione was the first biological peptide synthesized in the laboratory, and the development of new synthetic methods allowed for the synthesis of longer peptide chains, such as oxytocin and insulin [2]. Although peptides are distinguished from proteins by their shorter length, the cut-off number of amino acids to establish the classification as peptide is arbitrary [3]. According to the Food and Drug Administration (FDA), which is responsible for the regulation of health products, proteins are amino acid polymers with a specific defined sequence that is greater than 40 amino acids in size [4]. Peptides became popular in cosmetic products due to their bioactive properties, as they are able to interact with skin cells by multiple mechanisms, present high potency at low dosage and because their size is thought to achieve a moderate penetration into the upper skin layers. Due to their hydrophilic properties, chemical modifications such as esterification with alkyl chains, may be required to enhance penetration [5,6]. Furthermore, there are peptides whose structure is inspired by naturally occurring molecules, such as matrikines originating from the fragmentation of extracellular matrix, which is a relevant trend in the cosmetic industry [7]. However, most peptides are actually obtained by chemical synthesis or biotechnology processing [8].
Peptides started being incorporated in cosmetic products during the late 1980s with the use of copper glycine-histidine-lysine (Cu-GHK). However, these ingredients did not earn notoriety in cosmetic products until the beginning of 2000, when Palmitoyl Pentapeptide-4 was launched, proposing to reduce facial wrinkles [9].
Currently, there are a wide variety of peptides available as cosmetic ingredients, which can be categorized according to their mechanism of action [6,8,9,10,11]:
Regarding safety, although some proteins are linked to skin allergy, including contact dermatitis, we were unable to find any evidence that peptides used in cosmetics may raise any concerns in this regard [12,13]. Moreover, protein hydrolysates, which contain bioactive peptides, are categorized as Generally Recognized as Safe (GRAS) by the FDA [7].
Nowadays, the “European glossary of common ingredient names for use in the labelling of cosmetic products” contains 848 entries with the word “peptide” [14]. Given the vast diversity of peptides available for cosmetic products, this study aimed to understand how the composition of anti-aging formulations has changed in recent years for these ingredients. For this purpose, an exploratory analysis of a pool of anti-aging products corresponding exclusively to multinational brands was performed. To our knowledge, this is the first study to describe the trends in the composition of cosmetic products on the market regarding anti-aging peptides.
Data were collected from anti-aging products from multinational manufacturers, marketed in parapharmacies and pharmacies from Portugal. Anti-aging cosmetics were included in the study if they exhibited on the label one of the following words: anti-wrinkle(s); anti-age/anti-aging; wrinkle repair; regenerator; aging; anti-slackening; firming. All the information available on the products’ labels was collected from the manufacturers’ websites. The data collection started in 2011 and was updated with products launched in 2018 or whose composition has been reformulated that year in order to avoid duplicate product analysis and to reflect the market trends. Cosmetics for application on the face, neck and eye contour were included, comprising more than 40 multinational brands. Following these criteria, 280 products were selected, 177 and 103 in 2011 and 2018, respectively.
The peptides contained in the cosmetic products collected during the study were listed according to the International Nomenclature of Cosmetic Ingredients (INCI) and commercial names. Afterwards, the data were analyzed with respect to the following parameters.
The relative amount of cosmetic products containing peptides and the occurrence of combinations of these ingredients were assessed and expressed in percentage.
The analysis focused on the twelve peptides with the highest usage frequency among the selected products in both years. The overall usage frequency for each peptide was determined by the sum of the number of products containing that specific ingredient in 2011 and 2018, and then they were ranked in descending order.
Peptides were categorized according to their sources, based on the information provided by the manufacturer or mentioned in scientific literature.
All peptides found in the periods of analysis were categorized according to the mechanism of action [9,15]. The anti-aging benefits of each peptide were searched on the following online databases: PubMed, Google Scholar, Scopus, Cochrane and KOSMET, using the following keywords: “peptide INCI name” AND (“skin” OR “topical”) AND aging. Given the innovative nature of these ingredients and the lack of peer-reviewed articles for some of the peptides found in marketed products, the manufacturers’ technical data sheets and brochures were also analyzed.
Between 2011 and 2018, the percentage of anti-aging cosmetic products containing peptides was raised from 23.5% to 25.2%. Furthermore, the number of products containing two or more peptides was also raised from 8.2% to 15.5%, showing an 88.5% increase.
The prevalence of products containing peptides on anti-aging products marketed in 2011 and 2018. The percentage of products containing only one peptide (1) is represented in green, and the percentage of products containing two or more peptides (2+) is represented in orange. In 2018, there was also a greater diversity of peptides amongst anti-aging cosmetic products, as we were able to identify 29 different peptides versus the 14 peptides identified in 2011 (not illustrated), which represents more than a two-fold increase. Overall, 37 different peptides were used.
Overall, the most used peptides during the seven-year period for anti-aging cosmetics were Palmitoyl Tetrapeptide-7, Palmitoyl Oligopeptide, Nicotiana benthamiana Hexapeptide-40 SH-Oligopeptide-1 and Palmitoyl Tripeptide-1.
Top peptides included in the composition of anti-aging products marketed in 2011 and 2018.
In 2011, the most used peptides were Palmitoyl Oligopeptide, Palmitoyl Tetrapeptide-7 and Acetyl Hexapeptide-8. In 2018, the pole positions were occupied by Palmitoyl Tetrapeptide-7, Nicotiana benthamiana Hexapeptide-40 SH-Oligopeptide-1 and Palmitoyl Tripeptide-1.
Tripeptide-1, Dipeptide-2 and Pimpinella anisium extract (apiacea peptides) were used in 2011 but did not appear in products launched in 2018.
The majority of peptides launched in 2011 are obtained through chemical synthesis. Conversely, in 2018, there were more peptides that originated from biotechnology than synthetic ones. It is noteworthy that there is a significant amount of peptides found in both years whose source is unknown.
Sources of peptides.
Signal peptides were the most used in both years, followed by neurotransmitter-inhibiting and carrier peptides. Contrary to the signal and carrier categories, the use of neurotransmitter-inhibiting peptides seems to be decreasing. We were unable to find enzyme-inhibiting peptides in this analysis.
Mechanisms of action for peptides found in anti-aging products marketed in 2011 and 2018.
The information regarding all peptides present in the composition of the analyzed anti-aging products is summarized on Table 1.
Summary of bioactive peptides used in anti-aging products marketed in 2011 and 2018.
This study explored the trending peptides used by the cosmetic industry in anti-aging formulations from the Portuguese market, which mainly encompasses multinational brands. From 2011 to 2018, the use of peptides in anti-aging products presented a small increase, reaching one fourth of the formulations on the market. However, the diversity of peptides almost doubled in these products, which reflects the growing importance of these ingredients in the period of analysis. The number of peptide combinations also followed this tendency. This observation may also be related with the use of peptide mixtures from ingredient suppliers, which often contain more than one peptide. There are 848 entries with the word “peptide” in the “European glossary of common ingredient names for use in the labelling of cosmetic products”, but this study only identified 37 compounds, which corresponds to 4.4%. This may relate to the fact that this study is restricted to the anti-aging market and/or it may portray the lack of relevance of many peptides commercially available for cosmetic formulators.
In 2011, “Palmitoyl oligopeptide” was the most used peptide in cosmetic products, but this ingredient is hardly found in products released in 2018. This is possibly related to the fact that the term “Palmitoyl oligopeptide” was “removed” in 2013, as it has been used to designate two distinct molecules since its development in 1994. Those compounds were renamed as Palmitoyl Tripeptide-1 (Pal-GHK) and Palmitoyl hexapeptide-12 (Pal-KTTKS) in order to avoid misunderstandings. With this in mind, we found that the second most used peptide in 2018 was Palmitoyl Tripeptide-1, which demonstrates that this ingredient is still being used by formulators [40]. Curiously, the ingredient “Palmitoyl Oligopeptide” was still found in the composition of one product launched in 2018. Both matrikine-mimetic peptides act by stimulating fibroblast activity, thus increasing matrix protein and glycosaminoglycan synthesis in the dermis. Palmitoyl Tripeptide-1 has shown the ability to stimulate collagen synthesis in a human fibroblast culture and prevent its degradation after the exposure to UVA light [41]. Furthermore, Palmitoyl Tripeptide-1 has been tested in a clinical study involving 23 healthy female volunteers, at 4 ppm, promoting a small but statistically significant increase in skin thickness of about 4% [41]. Palmitoyl hexapeptide-12 is an elastin fragment used to stimulate collagen and elastin synthesis, as well as fibronectin and glycosaminoglycans. In a double-blind study, a group of 10 female volunteers performed two daily applications of an emulsion containing 4% Palmitoyl hexapeptide-12 or a placebo for one month. The application of the test product improved skin elasticity and firmness. However, the supplier did not provide the study methodology nor reported if these improvements had statistical significance [16].
The second most used peptide in 2011 was Palmitoyl Tetrapeptide-7, which in 2018 i
