- 01What Peptides Can Do for Your Skin
- 02Not All Peptides Are Equal
- 03Signal Peptides: Matrixyl 3000 is Best in Class
- 04Neurotransmitter Inhibiting Peptides: Argireline is Best in Class
- 05Carrier Peptides: GHK-Cu is Best in Class
- 06Enzyme Inhibitor Peptides: Rice Peptides Among Best in Class
- 07Why You Need All Four Classes
- 08How to Use Peptides in Your Routine
- 09Why Not One Serum for Everything?
- 10Who Should Use a Peptide Serum?
- 11Do Peptides Cause Inflammation?
If you just want the Cliff's Notes version, check out our casual guide to peptides. Otherwise, read on — we're going deep.
Peptide products can be hydrating and anti-aging
Peptides are good humectants which means they are good at attracting water and holding onto it. A subset of peptides also help reduce wrinkles.
Depending on the peptides included, a peptide serum can either be hydrating or both hydrating and anti-aging. If you want anti-aging benefits, then look for peptides that fight wrinkles in one of four ways.
Signal peptides, neurotransmitter inhibiting peptides, carrier peptides, and enzyme inhibitor peptides are the four classes of anti-aging peptides (Gorouhi and Maibach 2009, Ferreira et al. 2020, Schagen et al. 2017).
Peptides are mini-proteins — and some are much more validated than others
The word "peptide" basically means mini-protein. If you chop up a protein into smaller pieces, you get peptides. For example, collagen is a protein. If you chop up collagen into little pieces, you get collagen peptides.
Both proteins and peptides are made up of amino acids which form chains when linked together. If the chains of amino acids are less than 50 amino acids in length, we call them "peptides." If longer, we call them "proteins."
Now imagine if you asked someone what they were having for dinner and they answered back "proteins." That would be pretty uninformative, right? The same is true for peptide serums. It's not an informative moniker.
So unless you look at the specifics, you won't know much about a peptide serum. Not all peptide serums are equal and there can be large differences between any two peptide serums. For example, even when just looking at the subset of anti-aging peptides, there are more than 50 different anti-aging peptides available in various products on the market today.
The vast majority of peptides have no scientific backing except for a few studies conducted by the company that sells that particular peptide. Stick with the peptides that are the most validated with a long history of unbiased scientific study by hospitals and universities. The ones that are best studied are also likely the ones naturally found in the skin — and so are less likely to have unknown negative effects.
About signal peptides: pal-GHK and pal-GQPR found in Matrixyl 3000 are best in class
So first, let's cover Signal Peptides. Remember when we told you earlier that if you chop up collagen into little pieces, you get collagen peptides? Well these collagen peptides can signal the production of collagen making them signal peptides.
So how do collagen peptides help build more collagen? When you get a skin injury, broken fragments of collagen are naturally released. Your body sees these pieces, thinks you have a wound, and pumps out more collagen to help heal it. When using these collagen fragments, you are taking advantage of your skin's natural wound healing mechanisms — but for anti-aging purposes.
The reason you get wrinkles as you age is that the long and rigid collagen fibers in the inner layer of your skin called the dermis decrease in number and degrade so that they no longer hold up your skin. Think of collagen fibers as tent poles. If you take away some tent poles and break the remaining ones up into smaller pieces, your tent is going to start to sag. That's basically what is happening to your skin as you age.
Not to overly complicate matters, but other than collagen, there are a couple other proteins in the dermis that are also important. These include elastin (which is important for making your skin stretchy with bounceback), and glycosaminoglycans (GAGs) such as hyaluronic acid which hold water and make your skin hydrated and turgid. And a few others too like proteoglycans, fibronectin and laminin.
All of these also decrease with aging. And all these components form something called the extracellular matrix (ECM). These ECM components are secreted by specialized cells in the dermis called fibroblasts. So to restore your skin to youthfulness, you want to encourage fibroblasts to secrete more of these ECM components, especially collagen.
Signal peptides do just that. As a class, signal peptides are collagen or other ECM fragments which signal fibroblasts to increase the production of collagen, elastin, GAGs, and other components of the ECM including proteoglycans, fibronectin and laminin (Errante et al. 2020, Gorouhi and Maibach 2009).
The history of Matrixyl
One of the first signal peptides was described in 1993 when a subfragment of type 1 collagen was found to stimulate fibroblasts to secrete type 1 and 3 collagen and fibronectin. To help this peptide cross the skin barrier, it was linked to palmitic acid and then proven in double-blind clinical trials to decrease wrinkle depth and density. This signal peptide pal-KTTS was originally sold by the company Sederma as Matrixyl (Huang and Miller 2007). You might see the original Matrixyl peptide included in some older peptide products.
In more recent years, another collagen fragment, pal-GHK has become more favored. GHK stands for glycyl-L-histidyl-L-lysine — glycine, L-histidine, and L-lysine are all amino acids. So GHK is a short peptide that is three amino acids long. For context, collagen fibers consist of long protein chains at least a thousand amino acids long that are braided together. GHK is a really tiny fragment.
Here is the thing about GHK. At the site of skin injury, your body activates enzymes that specifically cut GHK from collagen. GHK then stimulates healing. In other words, this particular fragment works better than other collagen fragments because your body is naturally geared to respond to it with healing processes (Pickart et al. 2015b).
GHK was first discovered in blood plasma way back in 1973 (Pickart and Thaler 1973) and its collagen and ECM stimulating properties were first described way back in 1985 (Maquart et al. 1999). GHK can stimulate skin dermal fibroblasts to produce growth factors and increase collagen and GAG synthesis (Pickart and Margolina 2018, Lintner 2002, Errante 2020, Sederma Matrixyl 3000). So, GHK is the best and longest studied signal peptide.
GHK content is highest in the young and declines with aging. In men aged 20–25, average plasma GHK was found to be 200µg/L — but in men aged 60–80, levels were only 80µg/L (Pickart et al. 2015b). This natural decline with aging may in part explain why adding GHK back to the skin can reverse signs of aging.
When you apply GHK to your skin topically, it isn't the exact same copy of what is naturally found inside your body. This is because it has a fatty acid called palmitic acid linked to it in order to form pal-GHK. The reason it is engineered in this way is because topicals have to cross the waterproof skin barrier on the surface of your skin. Peptides just don't do that easily, but fatty acids do. So by linking to a fatty acid, the peptide can now enter into your skin. Pal-GHK has been used in anti-aging and cosmetic products in humans for decades without any adverse effects (Pickart and Margolina 2018), giving it an established safety record.
Why Matrixyl 3000 outperforms GHK alone
Matrixyl 3000 is pal-GHK combined with another peptide, pal-GQPR. Why the combination? Well, it was found that combining pal-GHK with pal-GQPR could boost the total amount of collagen production. In fact, the amount of collagen, fibronectin and hyaluronic acid production stimulated by applying both was much greater than the sum of production stimulated by each acting alone. In other words, 1 + 1 = 3 (US patent 2004/0132667 A1). This is called synergy — a phenomenon common to skincare and medicine.
GQPR is a fragment of antibody protein immunoglobulin G naturally found in your body. GQPR is immunomodulatory. As skin ages, there is an increase in inflammatory cytokine IL-6, which may contribute to chronic inflammation in the aging process. The putative mechanism by which pal-GQPR works is by reducing IL-6 secretion by keratinocytes. However, like GHK, GQPR changes the expression of multiple genes and so it has a broad effect on fibroblast activity that goes beyond anti-inflammatory action (Schagen 2016).
It's not fully understood how it boosts the efficacy of GHK. Sederma conducted a study that provides a clue — they showed that pal-GQPR and pal-GHK activated different but complementary genes (Sederma Matrixyl 3000). Maybe you have a friend like this who is very different from you but somehow has qualities that complement your own.
Clinical evidence for Matrixyl 3000
Subsequent placebo-controlled clinical studies in both men and women showed Matrixyl 3000 performed well in significantly decreasing wrinkle depth and volume as well as skin roughness.
We think Matrixyl 3000 is the standout in this class. First, GHK is the best studied and naturally found signal peptide with the most unbiased scientific studies supporting it. Second, Matrixyl 3000 boosts GHK performance through synergy. Finally, it performs well in clinical trials. In ingredient lists, look for palmitoyl tripeptide-1 (pal-GHK) and palmitoyl tripeptide-7 (pal-GQPR). Both are included in Peptide Squad.
Neurotransmitter inhibiting peptides relax away wrinkles — Argireline is best in class
Neurotransmitter inhibiting peptides are sometimes informally called "botox-like" because they have the same target as botox. They aim to inhibit muscle activity to limit expression lines.
Dermatologists hate the term "botox-like" because botox injections are much more effective and longer lasting than anything topical. Let's be honest here: if you really want botox-like results, then you should get botox injections. But hold on — even if you get regular botox injections, I have something to tell you that I know you will want to hear. And for those of you who want to avoid botox injections, these topical peptides are a safe, non-toxic alternative (Blanes-Mira et al. 2002).
The principles behind these neurotransmitter inhibiting peptides are similar to that of botox in that they aim to act on the cholinergic neuromuscular junction (NMJ) to inhibit muscle activity. For neurotransmitter acetylcholine to be released at the NMJ, a reaction cascade mediated by SNAP receptor proteins and SNARE complex formation is necessary. SNAP-25 specifically is targeted by both botulinum neurotoxin type A (botox) and peptide Argireline.
Argireline competes with the SNARE complex by mimicking the N terminal end of SNAP-25 — hence preventing formation of the SNARE protein complex and inhibiting acetylcholine release and subsequent muscle contraction (Lipotec Argireline).
Why Argireline stands out
Similar to other peptides in this class, clinical studies conducted by the manufacturer demonstrate reduced expression wrinkles around the eyes with usage of Argireline creams (Lipotec Argireline). Further, other published academic clinical studies show its anti-wrinkle efficacy whether formulated alone (Blanes-Mira et al. 2002, Tadini et al. 2015) or in a mix of peptides (Draelos et al. 2016, Errante et al. 2020).
Most interesting to us however was a double-blind, placebo-controlled, randomized study conducted by the National Institutes of Health in patients with a condition called "blepharospasm" (Lungu et al. 2013). Blepharospasm is a condition in which you have excessive blinking or twitching or other eyelid movements that you can't control. If severe enough, patients are treated with regular botox injections into the eyelid muscles.
In this study, some patients got a placebo cream and some got a cream with Argireline right after their botox injection. Those who used the Argireline cream had better control of their eyelid movements for longer than those who used placebo.
If you get regular botox injections, this NIH study suggests that applying Argireline regularly afterwards can extend how long the benefits of botox last — so you can get injections less frequently, saving you time and money.
Other neurotransmitter inhibiting peptides targeting the NMJ include Pentapeptide-3 (Vialox), Pentapeptide-18 (Leuphasyl), Tripeptide-3 (SYN-AKE), Acetyl Octapeptide-3 (SNAP-8), Palmitoyl Heptapeptide-18 and Palmitoyl Hexapeptide-52 (X50 Myocept CC), and Acetyl Hexapeptide-30 (Inyline). These have all been found to have anti-wrinkle activity in clinical studies and are all fine choices. Nonetheless, in this class, we believe Argireline has the best track record because of the unbiased scientific studies conducted outside the manufacturer that show it works.
For these reasons, we include Argireline in both our Peptide Squad serum as well as our Eye Enhancer gel cream. The INCI name for Argireline is acetyl hexapeptide-8 or acetyl hexapeptide-3 — look for either of these names on the ingredient list.
Carrier peptides carry copper to the skin — GHK-Cu is best in class
In recent years, people have become more and more excited about copper peptides and with good reason. Copper peptides are called carrier peptides because they carry copper to the areas of skin where it is needed. The clear standout here is GHK-Cu, also known as copper tripeptide-1.
GHK-Cu is actually a natural carrier peptide already in your skin that is involved in wound healing. Typically, you ingest small amounts of copper through your diet and the copper goes into your bloodstream. Eventually, that copper is carried to your skin by GHK-Cu. Think of it like an Uber delivering copper home after a pickup at the airport — copper needs to be carried from one place to another. However, these natural levels of GHK-Cu drop as you age. So less Ubers, less copper delivery to your skin.
And here is another thing: if you apply it topically, it has been found that GHK-Cu can cross into the skin in sufficient quantities to deliver copper to your skin directly and compensate for this decline (Pickart et al. 2015ab).
GHK-Cu is the carrier system your body uses to bring copper to your skin as a natural part of wound healing. It stimulates the whole process of wound healing including support of the breakdown of scar tissue and promotion of collagen synthesis, as well as elastin, proteoglycan and GAG production (Gorouhi and Maibach 2009, Pickart et al. 2015b). Further, while GHK-Cu may serve as a natural built-in modulator of dermal repair, the levels decrease with age (Freedman et al. 1982, Pickart et al. 2015ab).
Why copper matters for collagen
Copper is essential for the enzymes in your skin to form mature collagen fibers. In other words, no copper, no mature collagen fibers. Even small concentrations of GHK-Cu can stimulate increases in collagen fibers and clinical studies show topical GHK-Cu can decrease wrinkle volume to an extent comparable to retinoids (Badenhorst et al. 2016, Abdulghani et al 1998, Leydon et al. 2002).
A caution about other copper peptides
Not all copper is good copper. Without a carrier, copper can go from hero to zero and cause both damage to cells and inflammation (Li et al. 2016, Pickart et al. 2015). One study looked at GHK-Cu and two other copper compounds — the other two stimulated inflammation and damage to skin cells, and only GHK-Cu did not (Li et al. 2016). Other copper peptides (such as encapsulated copper peptides / encapsulated lipopeptide Copper Palmitoyl Heptapeptide-14) are not as well-researched and are not naturally found in skin. We don't feel comfortable advocating for them.
In your skin, the safe delivery of copper is trusted to GHK-Cu. GHK-Cu is like riding with a chauffeur you have trusted all the years of your life. Whereas, other copper peptides are like hitchhiking a ride with a stranger. You are taking a risk — and we don't think that risk is worth it.
Peptide Squad with GHK-Cu can be used with our Glow Maker Vitamin C Serum. So stick with the tried and true GHK-Cu. The INCI name is copper tripeptide-1 — look for that in your ingredient lists.
Enzyme inhibitor peptides block collagen breakdown — rice peptides are among the best in class
Now imagine that a tree damages your roof. What's the first thing you need to do before getting a new roof? You need to remove the damaged parts. This is what enzymes called matrix metalloproteinases (MMPs) do.
In younger skin, the activities of MMPs are well controlled and are useful for wound healing when you need to purge damaged skin so new skin can grow. However, as you age, MMPs become excessively active and start attacking healthy collagen (Varani et al. 2006). In other words, one of the reasons you get wrinkles as you age is that MMPs go berserk and start ripping up the new roof you just put in.
This is where enzyme inhibitor peptides come in. They inhibit MMPs. Studies show rice and soybean peptides inhibit MMPs (Schagen 2017, Ferreira 2020). Further, not only do rice peptides inhibit MMPs, they also stimulate production of glycosaminoglycans like hyaluronic acid by stimulating hyaluronan synthase, as well as having anti-tyrosinase activity for hyperpigmentation (Schagen 2017). Rice oligos with Vitamin C in ampoules have also been tested in humans with positive findings (Escobar et al. 2020), and rice peptides are also very good natural humectants (Purnawati et al. 2017).
Particularly in East Asia, rice peptides have been used for thousands of years — going back to ancient times when women in the royal court used rice water to maintain their skin. Rice peptides have been incorporated into popular luxury skincare products in East Asia for decades. We include rice peptides in Peptide Squad serum.
If each class of peptides fights wrinkles, why do you need all four classes?
Many of the serums on the market will contain only one or two classes of wrinkle fighting peptides. In contrast, Peptide Squad combines all four classes in one bottle. Does it matter?
Well, it matters because of the concept we mentioned earlier: synergy. Serums and creams are not magic. They aren't plastic surgery. They aren't injections. They require consistent and prolonged usage to really see results from small effects that build up over time. The greater the effect of each application, the faster you will see results and the greater that result will be.
At Maelove, we are known for products that work. And the way we achieve that is through synergies — that is when 1 + 1 = 3. The best way to get synergies is to combine ingredients that help a problem but in different ways. Combining all four classes does just that. Each class helps fight wrinkles via a different mechanism.
It would be like trying to get healthier. Maybe you go to yoga class twice a week. You would get good results from it. But let's say you also started to eat more vegetables, lift weights, do some cardio, and skip dessert. Which would get you the better result faster? Just the yoga, or the yoga combined with all these other actions? It's a no brainer. If you want to get results you can see from topicals, you want to attack the problem from many directions.
How should you use peptides in your routine?
Your other best friends in the fight against wrinkles are what we call your Vitamin ABCs of anti-aging: Vitamin A (retinoids), Vitamin B3 Niacinamide, and Vitamin C. Both peptides and Vitamins ABC are scientifically proven anti-aging ingredients that help build collagen and fight wrinkles. Additionally, Vitamin C antioxidant serums will protect against UV damage, Niacinamide will strengthen the skin barrier, and retinoids thicken skin and increase blood flow. We believe that a winning combo is to use all of the above.
Now, there are many reasons to not use all of the above. For example, those who are pregnant or lactating should avoid retinoids. Those with sensitive skin may find retinoids and Vitamin C too irritating to use. So it really matters case by case. In general though, the more you can tackle aging skin from different angles, the better an overall result you will get.
Think of collagen building like filling a lake with a hose. The larger the wrinkles, the deeper the lake. If the lake is small, one hose may be sufficient. But what if one hose is not enough? What's better, one hose or four? You'll get better results if you combine peptides and vitamins.
At Maelove, we design our serums to layer on top of one another so you can build what we call multilayer combination therapy. Maelove serums are designed to go thinnest to thickest.
Combination therapy is something used throughout medicine and healthcare where you combine treatments to fix a problem from many different angles. It's like the Avengers — a team of superheroes that each have a unique power and together can fight off the bad guys. It's much more effective to have a team than just having one superhero. The combination also introduces synergies which means they can boost one another to be better than they would otherwise be alone. Combination therapy is the scientifically proven latest and best way to tackle cancer — and you guessed it — problems in skincare.
Why can't you just use one serum that combines every anti-aging ingredient?
Here is one example we saw of a company advertising their Vitamin C serum as better than others because it also contained Niacinamide. If you've read our newsletters, you know this should set off alarm bells. For Vitamin C to permeate skin, it needs to be in a serum with a pH of 3.5 or lower. However, at this low pH, niacinamide will break down into niacin within the bottle. Niacin is a well known skin irritant that causes itching and flushing.
So either this serum does not provide the right conditions for Vitamin C to penetrate the skin, or it does not provide the right conditions for Niacinamide to be stable in the formulation. In other words, some ingredients should not be formulated together — and if they are, that signals to you that the serum is likely worthless.
Different ingredients — and especially Vitamin C and Retinoids — often need special treatment. There are several factors to consider including sensitivity to degradation from light and air, optimal pH, solubility, levels of irritation for sensitive skin, safety during pregnancy, how long it takes to acclimate to the ingredient, whether you should apply in the morning or evening, and more.
In general, you want your Vitamin C serum and your retinoid serum to be distinct serums from one another and distinct from your copper peptides serum. Niacinamide in contrast can be co-formulated with your copper peptides serum — as it is in Peptide Squad. Lean towards the layering method, not the all-in-one method.
Who should use a peptide serum?
First off, peptide serums are anti-aging solutions that can work for basically everyone. This includes pregnant and lactating women, and people with sensitive skin. With a serum like Peptide Squad, some may notice an initial numbing or tingling sensation. Don't worry — this is a normal reaction to Argireline, the neurotransmitter inhibiting peptide.
Don't worry also if you don't feel a tingle. That's also normal. It has nothing to do with efficacy, and rather just your particular skin sensitivity. The numbing or tingle will quickly fade.
Otherwise, peptide serums should be non-irritating and in the case of Peptide Squad, it is formulated with skin soothing and anti-inflammatory ingredients such as niacinamide, panthenol, bisabolol, madecassoside, red algae and botanical extracts that should calm and soothe your skin further.
You can use peptide serums in the morning or in the evening or anytime also during the day. With a serum like Peptide Squad, we like to use it basically whenever — including whenever skin feels dry, as it is also highly hydrating. We extended the natural hydrating power of peptides with other natural moisturizing factors, hyaluronic acid, ceramides, and jojoba oil.
There is no acclimation period with Peptide Squad. You should start to reap benefits from Day 1, although many of the wrinkle fighting effects take consistent usage over time to fully develop.
Do peptides that mimic wound healing cause inflammation?
Some sites on the web say that since signal and carrier peptides are both naturally involved in wound healing, they can also cause inflammation which typically accompanies wounds.
Our point of view is that as long as you stick to the tried and true peptides mentioned earlier, the exact opposite has been shown to be true. Both GHK and GHK-Cu have been found to be both anti-inflammatory and antioxidant. GHK has anti-inflammatory benefits by reducing TNF-alpha induced secretion of proinflammatory cytokine IL-6 in dermal fibroblasts, and GHK is an efficient antioxidant, inactivating damaging free radical by-products of lipid peroxidation (Pickart et al. 2015a, Pickart and Margolina 2018).
Further, GHK-Cu activates genes associated with further antioxidant activity (Pickart et al. 2015ab, Pickart and Margolina 2018).
As long as you stick with well-understood peptides, you don't have to worry about inflammation. In fact, these peptides provide the added benefits of anti-inflammatory and antioxidant properties.
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