Tag Archives: Collagen supplements

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.

Hair, Skin, and Nails Supplements Loaded with “Collagen,” Biotin, Vitamins – Wasting Money and Diminishing Your Health 

 Hair, skin, and nails (HSN) supplements are increasingly purchased despite limited evidence they work and evidence they are harmful, and suffer from lack of regulatory oversight. Stop substituting expensive, harmful supplements for a healthy whole plant-forward diet. And remember, collagen supplements don’t contain collagen, they contain amino acids and peptides (protein fragments).

Supplements marketed for skin, hair, and nail benefits, often called “dermatology” or “beauty” supplements, are increasingly being sold by unscrupulous and/or ignorant salespeople , with the global beauty supplement market expected to reach $7 billion by 2024 (Sanchez et al, 2020). So much money can be made selling these unregulated products that practicing physicians are stepping into this industry in large numbers. It’s a booming business where a supplement manufacturer makes a supplement, then recruits a physician to sell it – and then the marketing claim is made that the supplement is “doctor formulated.” It’s called a physician “side-gig” Despite the narrative that physicians are overworked, at least 40% of them have a side-gig in addition to their physician practice. What better way to make money than to stick your name on a bottle of supplements. Just ask Dr. Oz.

No U.S. Food and Drug Administration (FDA) approval or registration is required to produce and market a dietary supplement. There is no need for manufacturers to provide proof of safety or efficacy to sell these products. Since no approval is required, like other foods, there is no centralized database of currently available dietary supplements. While it’s hard to immediately harm yourself when eating natural foods, there is no restriction on concentrated doses of vitamins, minerals, and other ingredients that may be eaten, even for nutrients with defined tolerable upper limits (ULs). For example, high levels of vitamin B12 may cause lung cancer (Fanidi et al, 2019), and high levels of Vitamin B1 have been correlated with breast cancer (Tan et al, 2023). Many of these supplements contain iron, and common adverse effects of iron overdose are constipation, gastrointestinal upset, reduced zinc uptake, and iron overload in acquired hemochromatosis (iron can build in the skin and darken and damage it). Zinc toxicity is another problem with many attendant problems including poor cholesterol regulation. I could go on, but you get the idea.

There’s another problem too, of which many, consumers, physicians, and manufacturers alike, are unaware. Biotin (vitamin B7) is widely used in “nail” and “hair” supplements that the FDA has warned may cause interactions between biotin and certain laboratory tests, including those that test for cardiac function and thyroid function. There are numerous reports of biotin interference with laboratory testing, specifically with thyroid function tests. Most commonly, biotin use can result in falsely high levels of T4 and T3, and falsely low levels of TSH, leading to either a wrong diagnosis of hyperthyroidism or that the thyroid hormone dose is too high. Not interfering with such testing is important because thyroid hormone (T3 and T4) affects every cell and all the organs in your body.  

Considering collagen, it can be extracted from fish, pig and cattle skin, but wildly popular is the “bovine” variety. Interesting, Type II collagen from animals is used to induce inflammation and arthritis in animal studies – too much collagen is not good – think scleroderma. In this bovine collagen craze lies a veiled industry driving the destruction of tropical forests and fueling violence and human rights abuses in the Brazilian Amazon. When found out, according to the Bureau of Investigative Journalism, Vital Proteins, a major supplier of bovine “collagen,” said it would “end sourcing from the Amazon region effective immediately.” ​I ponder. Remember, it’s not collagen, rather the processed, hydrolyzed components of collagen, mainly some amino acids and peptides, is what the product really is. And those peptides will be broken down to amino acids in the gut, including by the gut’s enterocytes. As for fish “collagen,” many reports of reactions, including anaphylaxis, have been reported. Bovine “collagen” too.

Jennifer Aniston is the chief creative officer of Vital Proteins, a leading collagen brand owned by Nestlé that has been deforesting the Amazon.

For those who would like to know, otherwise you can skip this paragraph, here’s how hydrolyzed collagen is made according to Lopez et al (2019).. Denaturation of native collagen produces three α chains in their random coiled form. It can be observed by thermal treatment of collagen above 40 °C. Once the chains are separated, the hydrolysis is carried out by the action of proteolytic enzymes (alcalase, papain, pepsin, and others). The resulting product is commonly called hydrolyzed collagen (HC). It is composed of small peptides with low molecular weight 3–6 KDa. Its solubility and functional activity (antioxidant, antimicrobial) are related to the type and degree of hydrolysis as well as the type of enzyme used in the process. Another type of hydrolysis is by use of chemical products in acidic (acetic acid, hydrochloric acid, and phosphoric acid) or alkaline media. These two types of extraction are strongly corrosive and produce a high salt concentration in the final product after neutralization. Alternative methods of extraction consist in thermal treatment or applying high temperature and pressure to the protein. It includes subcritical water level (SCW) that exists at a temperature between 100 and 374 °C and a pressure of less than 22 MPa. More environmentally unfriendly steps in the production of “collagen” supplements.

You may have heard about a published, systematic review of clinical trials on oral collagen supplements. Like many studies of this type, the study claims their results support that ingesting hydrolyzed collagen can reduce skin wrinkles and improve elasticity and skin hydration. If you’ve read my papers, you know to ask an important question, “compared to what?”

This study was of taking oral hydrolyzed collagen and comparing it to doing nothing. Eat a lousy diet, take a supplement, and see some benefit. That’s what the study found. In other words, taking a supplement was compared to eating a lousy diet. Try this instead. 1. Eat a healthy diet versus a lousy diet and see what happens, and 2. compare that to the take a supplement with a lousy diet versus eat a lousy diet. Which one is better? Probably number one. Because taking a supplement only provides part of what a good diet provides.

Eat vegetables to provide all the nutrient your body needs to grow healthy hair.

Eating a combination of plant foods that can help with this include: