Tag Archives: collagen

Forget the Collagen Supplements for Skin Health – It’s All Pay to Play When the Studies Are Analyzed

A new study analyzing 23 randomized clinical trials with 1474 participants has found that “collagen supplements” significantly improved skin hydration, elasticity, and wrinkles only if you include data from physician-investigators who were paid by pharmaceutical/supplement companies. However, an analysis of studies not receiving funding from pharmaceutical companies revealed no effect of collagen supplements for improving skin hydration, elasticity, and wrinkles, while those receiving funding from pharmaceutical companies did show significant effects. Similarly, high-quality studies of “collagen supplements” revealed no significant effect in all categories, while low-quality studies revealed a significant improvement in elasticity.

No evidence that collagen supplements improve skin health

First, “collagen supplements” don’t contain collagen – they contain hydrolyzed collagen, otherwise known as amino acids. Moreover, most “collagen supplements” contain many ingredients other than the hydrolyzed collagen. A new meta-analysis by scientists at two major universities casts doubt on the effectiveness of “collagen supplements” for improving signs of skin aging, raising questions about the role of industry-funded research in shaping health and wellness trends. As the authors conclude, “There is currently no clinical evidence to support the use of “collagen supplements” to prevent or treat skin aging.” This is nothing new. Many studies in the pharmaceutical and supplement industries are flawed, frequently using fraudulent data, to sell their products that actually don’t work.

Often times, pharma and supplement companies hire ghostwriters to perform and write-up the study. Then the company finds a physician who will put their name on the byline. The physician didn’t have anything to do with the study and had nothing to do with writing the study. Ghostwriting is a big problem, and growing. For example, “first author” of a medical paper on Vioxx, Jeffrey Lisse, M.D., has said in an interview that “Merck designed the trial, paid for the trial, ran the trial…Merck came to me after the study was completed and said, ‘We want your help to work on the paper.’ The initial paper was written at Merck (ghostwritten), and then it was sent to me for editing.” In other words, Mr. Lisse was not an author of the study but was paid to pretend he was. Not only were his actions immoral, they were dangerous. Vioxx was later removed from the market because it significantly increases cardiovascular adverse events – people died from heart attacks. As physician Adriane Fugh-Berman, M.D., professor at Georgetown University School of Medicine and PharmedOut, has said about ghostwriting, “But there’s also the fact that this is so common that it’s not considered unusual. There’s no shame attached to it.” The point here is that many studies of drugs and supplements are flawed, some are fraudulent, and the studies of collagen supplements seem to be highly flawed.

Collagen and its importance to skin function and health

From: Han et al (2021) Recent advances in skin collagen: functionality and non-medical applications

Skin Collagen is a scleroprotein (not water soluble) and a major structural protein found throughout the body, including in skin (Fig. 2), hair, nails, tendons and bones. Much collagen in the body, including in the skin, is long-lived. One estimate of human skin collagen half-life suggested 14.8 years. Specifically, type I and type III collagen are found in abundance in the skin. Elastic fibers also play an important structural role within the dermis. Elastic fibers are composed of elastin and fibrillin microfibrils. In contrast to collagen, the biochemical configuration of elastin allows for gliding, stretching, and recoiling of fibers. The reticular dermis comprises thick elastic fibers. Two subtypes of elastic fibers are noteworthy: elaunin and oxytalan fibers. Elaunin fibers are horizontally arranged elastic fibers found near the junction of the papillary and reticular dermis. Oxytalan fibers are perpendicular elastic fibers found in the papillary dermis. Fibers work alongside substances like glycosaminoglycans (GAGs), such as hyaluronic acid, to maintain skin elasticity, volume, and moisture. While the body naturally produces collagen using amino acids from foods like beans and tofu, production declines with age and can be further reduced by sun exposure and poor diet.

From Alcaide-Ruggiero et al (2021). Schematic representation of collagen biosynthesis. (1) Gene transcription. (2) Formation of α-chains. (3) Formation of triple helix procollagen and secretion into extracellular space. (4) Procollagen processing and formation of tropocollagen (non-soluble form of collagen). (5) Association of tropocollagen molecules to form collagen structures.

Many forms of collagen, such as type I, are abundant through a range of tissues and are fundamental structural building blocks. Type I collagen is the main component of fibrils that provide tissues with tensile strength. Type I collagen is a heterotrimeric protein assembled from the two α1(I) and one α2(I) polypeptides when they fold into a triple helix. After secretion of procollagen into the extracellular space, the terminal domains are removed by proteolytic cleavage and the rodlike triple helices of the central domain polymerize into fibrils and are covalently cross-linked.

Type I collagen is the most abundant collagen type in the skin, accounting for 80–85% of the dermal ECM. Other subtypes, like type III and type V collagen, can be found in skin, but type I collagen is fundamental to skin structure; it supplies considerable tensile strength and helps to determine the structure and durability of the dermis. As skin ages, there is a progressive loss, damage, and fragmentation of dermal collagen fibrils, leading to reduced skin thickness and biomechanical strength.

Type I collagen is also one of the longest-lasting of the long-lived protein in humans, and is a major fibrillar component of connective tissues such as skin, bone, and tendons. It has a triple-helix structure composed of two α1 chains encoded by the Collagen type I alpha 1 chain (COL1A1) gene and one α2 chain encoded by the Collagen type I alpha 2 chain (COL1A2) gene. Among these, COL1A1 expression has been identified as a biomarker of skin aging, as its levels decline with age. This organization of collagen along with other fibrils and matrix molecules endows connective tissues with mechanical strength and elasticity.

Collagen genetics

The COL1A1 gene provides instructions for making part of type I collagen. A component of type I collagen called the pro-α1(I) chain is produced from the COL1A1 gene. Collagens begin as rope-like procollagen molecules that are each made up of three chains. Type I collagen is composed of two pro-α1(I) chains and one pro-α2(I) chain (which is produced from the COL1A2 gene).

The triple-stranded procollagen molecules are processed by enzymes in a series of steps inside and outside the cell to create mature collagen. The collagen molecules then arrange themselves into long, thin fibrils that form stable interactions (cross-links) with one another in the spaces between cells. The cross-links result in the formation of very strong type I collagen fibers.

Industry funded pharmaceutical and supplement studies are often flawed

While collagen drinks, supplements, topical products and even prescription pharmaceuticals have gained market traction for their promised skin benefits, the stark difference between the overall results and the subgroup findings underscores how industry funding and study quality can sway outcomes, a longstanding concern in nutrition, pharmaceutical, and supplement research. Sadly, many medicines and supplements don’t work, including those for dermatological use. Allen Rogers, PharmD, worldwide vice president of genetics at Glaxo SmithKline, is reported on the front page of the Independent (8 December, p 1) as saying: “Our drugs don’t work on most patients.”

Confounding these studies of collagen, most of the trials used commercially available supplements that contained more than hydrolyzed collagen (amino acids), including vitamins, minerals, antioxidants, coenzyme Q10, hyaluronic acid and chondroitin sulfate were among the additional ingredients.

Too much amino acid consumption is bad for health, including heart health

Scientists have discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. For example, amino-acid-mediated mammalian target of rapamycin (mTOR) signalling in macrophages has been implicated in the pathogenesis of ischemic cardiovascular disease. Specifically, ingestion of protein or amino acids in excess of ∼22% of dietary energy requirements drives atherosclerosis.

Further, an unbalanced, unnatural increased intake of one or more amino acids can cause imbalance in amino acid concentrations in the body, increase concentrations of its metabolites, and affect the transport of a group of amino acids into cells due to competition for a carrier at the cell membrane. The phenomenon of carrier competition can affect absorption of other amino acids in the gut and subsequently their appearance in the blood, transport across the blood-brain barrier, and supply for protein synthesis. Proteinopathies may result, leading to degenerative disorders. For example, too much leucine consumption can decrease autophagy in the brain. Autophagy, a cellular process of waste and debris removal, is known to decrease proteinopathy, and therefore too much leaucine may potentially lead to the buildup of toxic metabolites and neurodegeneration.

Summary

Skip the supplements made from hydrolyzed collagen. Eating a variety of plant-based protein sources—such as beans, soy, legumes and quinoa—means your body will have the amino acids it needs to make collagen, while also providing Vitamin C and antioxidants, all of which are important to the health status of the skin, particularly collagen formation and protection of the long-lived collagen.

Skin Cell Renewal and Collagen Production Without Injury

Wounding from procedures induces cellular replication, and replication may drive changes in cells and could push them toward a more tumorigenic state. “Tumors are wounds that don’t heal.”

Tissue specific stem and progenitor cells, such as the skin’s mesenchymal stem cells, fibroblasts, and keratinocytes, can persist during the lifetime or for extended periods of time in humans and contribute to both renewal and repair by giving rise to pools of progenitor cells that persist for various periods of time, replenish differentiated, i.e. mature cells, release many types of molecules involved in healing, and make short-term contribution to wound healing. Normally, these cell’s processes maintain and heal our skin throughout life. However, due to poor lifestyle, such as a diet that overfeeds us but under nourishes us, the nutrients needed to maintain proper function in these cells are lacking. Too much sun, leave-on products that are pro-inflammatory, and environmental exposures are other examples of lifestyle factors diminishing skin function. While hereditary and genetic factors may play a role, their contribution is minimal to developing diseases. Along with intrinsic aging, where our cells go through “wear and tear” to maintain themselves regardless of other impinging factors, what we do in life, i.e. our exposome is by far the most significant factor in maintaining health, including our skin health. Again, our exposome as a consequence of what we do in life, is the largest factor in our skin’s health. For example, if you don’t exercise, then the body won’t produce a normal complement of antioxidants. And, if you don’t eat a sufficient supply of fruits and vegetables, antioxidants will not be carried through the blood and pumped into the skin. And if you’ve induced chronic inflammation in the skin, perhaps through the continuous use of an inflammatory product or procedure, then the antioxidants and other nutrient may not be efficiently pumped from the blood supply into the skin. Yes, inflammation can interfere with the pumps in the blood vessels that bring nutrients from the blood supply into the skin.

As I have written, numerous studies have found that providing all the necessary nutrients, without an overabundance of calories, optimizes stem cell function in the body. Eating well also optimizes the cell function in cells other than stem cells, many of which act to support stem cell function. It’s all a tightly woven system, and the key here is to understand it’s a system. All of our cells work together. For example, even inflammation in the outer layers of the skin, the epidermis, leads to inflammation throughout the body. So what you do to your skin affects your whole body. If you’re using topical products that induce inflammation in the skin, you’re inducing inflammation in the body. If you’re having a procedure, such as laser, chemical peels or microneedling, you’re inducing inflammation in the skin and therefore inflammation in the body. As I have previously written, wounding the skin through the use of these procedures, induces not only inflammation, but proliferation too. This over-driving of cell proliferation leads to cellular exhaustion. Stem cell exhaustion or dysfunction increases with age, and especially with too many wounding procedures, and impedes the normal function of multiple tissues and systems. Dr. Leonard Hayflick, Ph.D., a professor at UCSF, discovered that cultured normal human cells have limited capacity to divide, after which they become senescent and can secrete inflammatory factors, a phenomenon now known as the ‘Hayflick limit’.  Increase inflammation and/or increase proliferation, and you can drive cells towards their Hayflick Limit. That’s what too many wounding procedures can do to the skin. Further, chronic inflammation coupled with chronic proliferation of cells is a hallmark of cancer.

If you are having one of these wounding procedures, something that can induce prolonged inflammation, I recommend using a product, such as NeoGenesis Recovery, that quells inflammation. Here’s why I recommend Recovery: Stem cell released molecules from adult stem cells derived from the skin are the key ingredient in Recovery. These molecules, the so-called S2RM technology, powerfully quell inflammation and reset the immune system from one of inflammation to one of anti-inflammation and pro-repair. The results are dramatic, and inflammation is quickly reduced. And because healing is hastened, proliferation is reduced too. Too much proliferation of the cells in the skin can lead to cellular exhaustion, senescence, and aging of the tissue. So key to healthy skin, particularly while we’re aging, is to control inflammation and, importantly, control the damage to the skin. Too many procedures that wound the skin, will lead to eventual aging of the skin. Thus, one may see short term positive effects, but long term negative consequences.

So how does one induce modest amounts of cellular turnover to remediate skin problems such as lines and wrinkles, sagging, and discoloration? The key is evolutionary science. How does mother nature naturally keep the skin healthy and keep the cells turning-over at a safe rate? The key is feeding the skin: from the inside-out through diet, and from outside-in through topical application of carefully chosen products. And what you feed the skin is critical. There is no magic bullet, not one ingredient alone that will yield the desired results. Rather, the skin is a system, composed of many different elements, each element depending on its own set of needs. So to feed the skin, many different ingredients are needed. For example, Vitamin C is needed as an antioxidant and also to induce the production of collagen as well as to facilitate the post-translational modification of the collagen protein that has been produced. There are other functions of Vitamin C in the skin as well. Many other antioxidants are present in the skin, and they work synergistically. To optimize the antioxidant capacity of the skin, and not to have too much of one thing, many antioxidants need to be fed to the skin. Too much of one can have disastrous results. Consider Vitamin E. Tocopherol and its esters are some of the most well described antioxidants and they are commonly used for their ability to minimize ultraviolet damage. However, overuse of Vitamin E can inhibit glutathione-S-transferase, responsible for the removal of cytotoxic compounds related to tumorigenesis in the skin. And if too much Vitamin C is present, then oxidative oxygen radicals are formed through interactions with other molecules in the tissue. The consequences of this Vitamin C overload and the production of oxidants is yet to be adequately described.

The bottom line is to use a combination of ingredients that are natural to the skin, and not overload on a single or just a few ingredients. This is the scientifically-based strategy that I use when formulating products for NeoGenesis. I use Vitamin C in some of our products to help in the natural production of collagen turmover and to repair those collagen fibrils that will be present for years to come. Some collagen protein is called long-lived protein and will remain in the skin for decades. It can accumulate damage over the years, and one way to protect it and repair it is with the use of multiple types of antioxidants. Therefore, when I formulate products, Neogenesis offers multiple types of antioxidants that work synergistically. Sometimes people ask me, why do the Neogenesis products have different colors, and why aren’t they all white and creamy like other products on the market? The simple answer, our products have a multitude of ingredients that are important to the skin and have different colors. Think about your diet. If everything you ate was white, you die pretty quickly from malnutrition because you’re not eating all of those colorful fruits and vegetables that provide colorful nutrients to the body. All of these ingredients are necessary for the natural turnover and repair of your skin’s cells. Mother nature gives you a balance of nutrients, and that is what we do at NeoGenesis.

At Neogenesis we offer safe and natural, mostly skin-identical, ingredients that support the natural turnover of the skin’s cells. Skin identical ingredients include the S2RM that our skin’s stem cells make and ceramide and urea that are made by other cells. Skin identical ingredients also include ingredients that our bodies don’t make, but are brought into the skin through diet, including vitamin C and carrotenoids. We don’t give you a product loaded with just one ingredient at high amounts, such as EGF so that face reddens and puffs up like a water balloon, nor do we offer a lip product loaded with gobs of peppermint oil to irritate, cause an inflammatory immune reaction, and swell the lips so that everyone looks like they have Melkersson-Rosenthal syndrome. A core technology that we use at Neogenesis is our S2RM technology. As our skin ages or is compromised by poor health and poor diet, our stem cell function can decline. The molecules that we use at NeoGenesis are from stem cells in the skin that help to induce collagen production, protect collagen, and help to control the turnover of keratinocytes in the epidermis that are key to barrier formation. So what we’re doing at NeoGenesis is simply returning to the skin what was naturally present when we were young and healthy. In this way we restore natural cellular turnover and collagen production, without the adverse side effects of inflammation and over-proliferation associated with wounding procedures. And remember, if you do have a wounding procedure, be sure to use NeoGenesis Recovery before and after the procedure to minimize inflammation, normalize proliferation, and reset the innate and adaptive immune systems of the skin to a pro-healing mode. Please avoid certain stem cell products that are made with pro-inflammatory and pro-oncogenic bone marrow mesenchymal stem cell cytokines. With the use of Recovery, better results are realized from the procedure with fewer adverse side effects and less down time.