Peptides vs. Retinol | Which is Better For Skin Health?

Looking for an expert comparison of the effects of peptides vs. retinol on the skin? Then stick around.

Many researchers wonder how peptides for skin care and anti-aging might perform against retinol in experimental settings.

Here we will break down the main mechanisms behind both retinoids and peptides, answering key questions like:

• Which is better for skincare—peptides or retinol?
• Should skincare peptides and retinol be used in tandem?
• What are the safety concerns associated with peptides and retinol?

We will also share the most clinically studied and effective peptides for skin care, as well as our most trusted sources of high-quality compounds for research.

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What is Peptide Therapy?

Peptide therapy may be defined as the clinical application of peptides, which are small proteins. Generally, a compound consisting of one polypeptide chain that is no more than 40 or 50 residues long is called a peptide. Like larger proteins, peptides are represented by three-dimensional structures that can target specific receptors and thus regulate different biological processes [1, 2].

The therapeutic potential of peptides has attracted great attention among clinicians and researchers alike. There are now over 60 peptide-based drugs that have been approved by the United States Food and Drug Administration (FDA) for human use, and hundreds of research peptides are pending investigation.

Peptides operate through various mechanisms, including by stimulating skin cell proliferation, augmenting collagen synthesis, preventing collagen degradation, activating growth factors, and directly inhibiting facial muscle contraction, resulting in diminished wrinkles and improved skin appearance [3].

Additionally, certain research peptides, such as GHK-Cu and epithalon, have been explored for their potential systemic benefits. These benefits encompass promoting longevity, facilitating wound healing and tissue recovery, aiding DNA repair, and potentially inhibiting tumorigenesis [4, 5, 6, 7, 8, 9].

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What is Retinol?

Retinol is a form of vitamin A that plays critical roles in vision, cell growth, immune function, and the healthy development of vital organs such as the heart and lungs [10].

Retinol is also widely known for its use in skin care due to its proven benefits for the skin [11]. Topical retinol can help improve the appearance of the skin by promoting epithelial cell proliferation and protecting against collagen degradation [12, 13].

Thus, retinol may help to address a variety of skin concerns, including:

1. Acne: By helping the skin shed dead cells and produce new ones, retinol prevents cells from clogging pores and creating conditions for acne formation. Retinoids such as retinol also have anti-inflammatory effects on the skin [14].
2. Wrinkles and fine lines: Retinol protects collagen against degradation and inhibits matrix metalloproteinase (MMP) activity. This helps reduce the appearance of wrinkles and fine lines [12].
3. Uneven skin tone and texture: By increasing the production of new skin cells, retinol may help fade dark spots, even out skin tone, smooth rough texture, and make the skin feel softer and smoother [13].

Retinol is not free of side effects and can cause skin irritation, dryness, and sun sensitivity, particularly during initiation of use or when applied in high concentrations.

Yet, retinol has a lower risk of side effects, but also lower efficacy compared to other retinoids, particularly tretinoin, which is reported to be about 10-fold more potent [11].

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Best Peptides For Skin Care

Below, we break down some of the more notable research peptides for anti-aging and skin care, including their corresponding mechanism and benefits.

GHK-Cu

GHK-Cu (glycyl-l-histidyl-l-lysine-copper), aka copper peptide, is found in human bodily fluids (blood, urine, saliva, etc.), and its levels appear to decline with age [15].

GHK-Cu was discovered in 1973 and has been found to stimulate dermal fibroblasts in the dermis and upregulate the production of collagen, elastin, and glycosaminoglycan—the main components of the intercellular matrix of tissues such as the skin [4].

It has also been reported to upregulate the breakdown of collagen and glycosaminoglycans. Therefore, it may work by increasing intracellular matrix turnover and replacing old matrix components with new ones [15].

GHK-Cu is likewise known to pass easily through the outer skin layers, thereby exerting its beneficial effects on the dermis when applied topically. Once there, it may act as an early signal for skin repair since its amino acid sequence is present in the alpha 2(I) chain of type I collagen, which is often broken down to GHK by injury-activated proteolytic enzymes [4].

In addition to its effects on the intercellular matrix, GHK-Cu may also have antioxidant and anti-inflammatory properties. Studies on cultured skin keratinocytes show that GHK-Cu protects them from reactive carbonyl species, protein glycation, and the photoaging effects of ultraviolet (UV)-radiation [16].

According to a review encompassing several clinical trials involving topical GHK-Cu, the peptide can provide several benefits for the skin, including [4]:

• Tightening loose skin
• Reversing thinning of aged skin
• Improving skin firmness, elasticity, and clarity
• Reducing fine lines and depth of wrinkles, and improving the structure of aged skin
• Smoothing rough skin and improve overall skin appearance
• Protecting against UV and photoaging
• Reducing photodamage, mottled hyperpigmentation, skin spots, and lesions

One randomized controlled trial reported that compared to a control serum, GHK-Cu applied topically twice daily in the course of 8 weeks reduced wrinkle volume by 55.8% and wrinkle depth by 32.8% in 40 female volunteers aged 40 to 65 years [17].

In addition, GHK-Cu is also available in injectable research peptide form. When applied via injections, GHK-Cu may exert systemic effects related to DNA repair, healing of wounds, lung tissue repair, angiogenesis, and nerve outgrowth [4].

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Epithalon

Epithalon (also known as Epitalon, Epithalamin, or AEDG peptide) upregulates telomerase activity and elongates telomeres in fibroblasts, with the effect of delaying aging processes in various cells, including skin fibroblasts [18, 19].

Research suggests that epithalon may increase the functional activity of skin fibroblasts, normalizing intracellular matrix hemostasis [20].

In addition, epithalon stimulates skin fibroblast proliferation and reduces apoptosis in organotypic cultures of skin cells from rats of different ages [21].

Researchers have suggested that these benefits may be due to the effects of epithalon on reducing the expression of the apoptosis-inducing caspase-3 and consequently MMP-9 (matrix metalloproteinase-9) in aged skin fibroblast cultures. In fact, epithalon lowers the expression of these proteins below the level observed in young cell cultures [22].

Analysis of the efficiency of topical epithalon formulations has shown that this peptide increases the moisture content in the skin's surface layers and visually reduces neck and face wrinkles in elderly women [22].

Epithalon is also available as an injectable compound for research purposes. It has been studied for its potential effects on sleep, chronic inflammation, longevity, aging-related conditions, DNA repair, and inhibition of tumor development [5, 6, 7, 8].

In Russia, the peptide has been reported to reduce mortality in elderly subjects. However, the subjects in this study were described as having a “rapidly aging cardiovascular system”, a description that does not correspond to a particular clinical diagnosis [9].

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Argireline

Acetyl Hexapeptide-3 (aka Acetyl Hexapeptide-8) is most commonly known by the brand name Argireline (trade name of the Spanish cosmetics firm Lipotec) [3].

It is a synthetic hexapeptide patterned from the N-terminal end of the protein SNAP-25 (synaptosome-associated protein 25kDa), which is a component of the SNARE (soluble NSF attachment protein receptor) complex [23].

Argireline acts as a competitive inhibitor of SNAP25, which prevents SNARE from facilitating synaptic vesicle Ca(2+)-dependent exocytosis for the release of neurotransmitters mediating muscle contractions such as acetylcholine [23].

By inhibiting acetylcholine release, the peptide can prevent facial muscle contraction and reduce visible wrinkles. This is a similar mechanism to the one exerted by the popular botulinum neurotoxins (BoNTs) produced by Clostridium botulinum that are used as injections for anti-wrinkle therapy [24].

Argireline appears to exert these functions when applied topically, without the need for injections—hence it being dubbed “Botox in a Bottle.” It is often marketed as a gentler, safer alternative to the botulinum toxin [3, 25].

Clinical studies report that the topical application of Argireline can significantly reduce wrinkle depth and appearance compared to placebo. Two notable trials involved the application of Argireline on one side of the face and an empty vehicle as a placebo on the other. The authors reported 30-50% wrinkle depth reduction with 10% Argireline emulsion applied twice daily for one month compared to 0-10% improvement on the control side [26, 27].

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Peptides Creams and Serums

Peptides for skin care and intervention against aging-related processes can often be studied as blended formulations found in creams and serums.

One notable research formulation is the Anti-Wrinkle Research Formula Cream by innovative peptide firm Limitless Life Nootropics.

Limitless is a research peptides vendor that is known for its high-quality and third-party tested compounds.

Their top-rated cream incorporates several peptides with potential skin revitalizing properties, including the aforementioned copper peptide (GHK-Cu) and acetyl hexapeptide-3 (Argireline). Here are some of its other notable components:

• SNAP-8: Also known as acetyl octapeptide-3 or acetyl octapeptide-1, SNAP-8 is another gentler, safer alternative to the botulinum toxin. It is also a competitive inhibitor of SNAP-25 and works by blocking acetylcholine release and facial muscle contraction.

  It has been reported to cause up to 65% reduction in wrinkle depth (mean 35%) and potentially exert a synergistic effect with another peptide called pentapeptide-18 (Leuphasyl) [3].

• Pentapeptide-18 (brand name Leuphasyl): Pentapeptide-18 also works by limiting muscle movement by blocking the release of acetylcholine in the neuromuscular synapses. It has been reported to act similarly to enkephalins, which bind to specific opioid receptors on pre-synaptic nerve terminals to decrease the amount of calcium entering the nerve terminal. It has been shown to result in about a 7% inhibition in facial muscle contraction, with the effect increasing up to 47% when combined with SNAP-8 [3].
• SYN-AKE: Also called tripeptide-3, it was discovered by Swiss researchers and designed to mimic the effect of waglerin-1, a polypeptide found in the venom of the Temple Viper. It works by reversibly blocking the muscular nicotinic acetylcholine receptors, inhibiting muscle contraction [28, 29]. There is evidence that a 28-day course of Syn-Ake reduces the visibility of wrinkles by up to 52% [3].
• Syn-Coll: Palmitoyl tripeptide-5, popular under the brand name Syn-Coll, is a synthetic peptide designed to stimulate the skin's production of collagen by stimulating transforming growth factor beta (TGF-β) [30]. Syn-Coll may also inhibit matrix metalloproteinases (MMPs), such as MMP1 and MMP3, that degrade collagen. By boosting collagen levels, Syn-Coll can help improve the firmness and elasticity of the skin [3]. It has also been reported to improve fine lines and wrinkles [31].

The combination of potent peptides with a wide range of beneficial effects make the Anti-Wrinkle Research Formula Cream a great asset in the experiments of researchers looking to investigate the synergistic effects of peptides on skin and anti-aging.

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Peptides vs. Retinol | Pros and Cons

Retinol and research peptides for modulating aging-related processes and skin care may share similar mechanisms that improve skin appearance. For example, retinol appears to reduce skin photoaging by inhibiting the UV-induced activation of MMPs that degrade collagen [32].

Similarly, palmitoyl tripeptide-5 (Syn-Coll) also inhibits MMPs to preserve and improve skin firmness and elasticity [3].

On the other hand, retinol also interacts with specific cellular receptors, such as Cellular Retinoic Acid Binding Protein (CRABP) types I and II, to upregulate skin cell proliferation and epidermal thickness [32].

Unlike retinol, topical peptides such as GHK-Cu may work to upregulate both the breakdown and synthesis of collagen and other intercellular matrix components, thereby increasing collagen turnover [15]. Many topical peptides also exert various mechanisms to block facial muscle contraction and prevent the formation of wrinkles [3].

Few studies have directly compared the benefits of peptides for skin care against the effects of retinol or other retinoids. One notable trial in 20 subjects compared the effects of the retinoid tretinoin, which is about 10x more potent than retinol, to the effects of GHK-Cu on dermal procollagen synthesis, epidermal proliferation, and inflammation.

After one month of therapy, 7 of the 10 subjects receiving GHK-Cu had increased procollagen production, compared to only 4 out of 10 individuals on retinoids. On the other hand, the retinoid stimulated epidermal proliferation and induced anti-inflammatory effects [33].

Pros and Cons of Retinol for Skin Care

Here are the main pros and cons of using topical retinol for skin care:

• Pros: Increases collagen formation, reduces collagen breakdown, exerts anti-inflammatory effects, and stimulates skin cell proliferation [32]. Topical retinol does not lead to systemic toxicity.
• Cons: May cause skin irritation in the form of peeling and erythema. The peeling from topical retinol is secondary to the hyper-proliferation of the epidermis mediated by retinoic acid receptor stimulation [34]. It may also cause photosensitivity, thereby forcing subjects to apply sunscreen products.

Pros and Cons of Peptides for Skin Care

Peptides for modulating aging-related processes also have specific pros and cons in regard to their use for skin care:

• Pros: Work via a variety of mechanisms which include induction of collagen and other intercellular matrix components synthesis, regulation of collagen breakdown, protection against active radicals and photoaging, and relaxation of facial muscles that may cause wrinkles and fine lines [3].
• Cons: Many of the compounds require further research in independent randomized controlled trials.

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Can Researchers Use Peptides + Retinol For Anti-Aging?

Unfortunately, there is a lack of research regarding the combined use of peptides and retinol for modulating aging-related processes in skin. Nevertheless, utilizing peptides and retinol together may be feasible based on their overlapping and potentially complementary effects.

While retinol affects epithelial cell proliferation and inhibits collagen degradation, peptides may augment this process by further enhancing collagen production and intercellular matrix components. Both retinol and peptides for skin care may also protect skin cells against inflammation, active radicals and photoaging.

However, it's worth noting that peptides such as palmitoyl tripeptide-5 (Syn-Coll) may further stimulate the proliferating effects of retinol and potentially increase the risk of side effects related to hyperproliferation.

Therefore, any research studies using these ingredients should be carefully designed to monitor for potential adverse reactions, and the concentration of these research compounds should be optimized to balance efficacy and safety.

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Peptides + Retinol | Side Effects and Safety

Researchers should be aware of the potential side effects associated with retinol and peptides for skin care and anti-aging before incorporating either or both in their experiments.

As mentioned, retinol may induce hyperproliferation of epidermal cells, which can lead to side effects such as scaling and peeling of the outermost layer of the skin [34].

In addition, retinol may also induce erythema and photosensitivity, especially soon after initiating retinol research. The risks appear to be dose-dependent, transitory and can be minimized or avoided by initiating retinol experiments with lower doses [35, 36].

According to the available research, topical peptides such as GHK-Cu, acetyl hexapeptide-3/8, palmitoyl tripeptide-5, and others do not appear to exert any side effects when applied topically. Moreover, the majority of these peptides do not penetrate deep within the skin and do not carry risks for systemic side effects [3, 16, 26, 30, 37].

Nevertheless, many research peptides for skin care and anti-aging lack extensive human trials and there are reasons for caution, especially for those considering investigating therapeutic uses of these peptides on a long-term basis.

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Retinoids and Peptides | FAQ

In this section, our peptide experts address some of the more commonly asked questions posed by researchers in the skincare and anti-aging space.

Are peptides better than retinol?

In general, peptides may be better than retinol in terms of wider therapeutic range and safety, as their topical use has not been associated with any side effects or safety concerns. At the same time, retinol is a potent inducer of skin cell proliferation which mediates many of its benefits for skin care. However, retinoid-associated hyper-proliferation may lead to adverse reactions, especially at high retinol concentrations.

Do peptides work the same as retinol?

No, retinol works primarily by interacting with specific receptors called Cellular Retinoic Acid Binding Protein (CRABP), which upregulates skin cell proliferation. It also reduces inflammation and prevents collagen breakdown. On the other hand, peptides have a variety of effects, and may increase collagen, elastin, and glycoprotein production, thereby increasing skin thickness and elasticity. Some act similarly to botulinum neurotoxins (BoNTs), preventing facial muscle contraction and wrinkle formation.

Should researchers use retinol and peptides?

There is a lack of research regarding the combined use of retinol and peptides. However, there is also no cogent reason to avoid the combination, and the different mechanisms of retinol and peptides for skin care and anti-aging may complement their effects.

Which peptide is best for anti-aging?

GHK-Cu stands out as one of the most potent anti-aging peptides that is highly effective when applied both topically and systemically in research settings. GHK-Cu injections have shown significant benefits in wound healing and tissue recovery research. Further, topical application has been reported to reduce wrinkle volume by 55.8% and wrinkle depth by 32.8% within 8 weeks in middle-aged test subjects.

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Peptides and Retinol | Verdict

Both retinol and peptides have shown significant benefits for skin care and anti-aging in experimental settings. Retinol appears to upregulate keratinocyte proliferation, protect collagen from degradation and reduce inflammation.

Research peptides exert various mechanisms depending on the specific compound, including upregulating collagen synthesis, reducing oxidative stress, and inducing relaxation in facial muscles to reduce the depth and volume of wrinkles.

Researchers looking to incorporate topical or injectable peptides into their anti-aging research are recommended to source high-quality compounds from trusted vendors such as Limitless Life Nootropics.

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