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Collagen is the most abundant protein in the body and the main structural protein of connective tissue. Supplementing with collagen improves arthritis symptoms and joint health and increases hair growth. Read on to see what else collagen benefits as well as how to increase collagen production.
What is Collagen?
Collagen Superfamily and the Extracellular Matrix
Tissues are made of more than just cells. Most of the volume within a tissue is comprised of the extracellular matrix (ECM), a diverse mesh of proteins and sugars produced by certain cells, which acts as the mortar binding our cells together [R].
The ECM is composed of two components, proteoglycans, and fibrous proteins. Collagens, elastins, fibronectins, and laminins are all fibrous proteins making up the scaffolding in the ECM. The proteoglycans fill in space in between [R].
Collagen is one of the many proteins embedded in the ECM. In fact, it is the most abundant protein in animal tissues. Thirty percent of the total protein mass in mammals is comprised of collagen [R].
The term collagen stems back to the Greek word kólla, meaning “glue” [R].
Collagen proteins are produced by animal connective tissue cells called fibroblasts. For a protein to be classified as a collagen, it must form the collagen-like triple helix and provide structural support in the ECM [R].
Tropocollagen is the basic building block of collagen. It is made from three peptides (groups of amino acids) strands that are coiled together in the form of a helix. These strands are known as alpha chains (α-chains) [R, R].
Collagenous region: This region is a series of three amino acids. The first amino acid, glycine, is the most important. The next two can be any amino acid but are usually proline and hydroxyproline. The repeating amino acid sequence is responsible for the helix structure of tropocollagen [R].
The three peptide strands of tropocollagen are glycine-rich. Foods containing high collagen levels also contain high glycine levels.
Non-collagenous region: This region lacks the repeating amino acid sequence required for the helix structure. Contains binding sites for other ECM molecules to interact with [R]. Multiple tropocollagens cross-links to form collagen fibrils [R].
Types of Collagen
Collagen is located throughout the body and has many known and unknown functions. Humans have 28 different types of collagen proteins and even more collagen-associated genes [R].
Some collagens are much more common than others. Over 80% of collagen is type I, II, or III, which are found mainly in the skin, bones, tendons, cartilage, lungs, intestines, and vascular system [R].
Type IV collagen is also very common, as it is a major component of the ECM produced by skin cells [R].
There are five major types of collagen:
- Type I
- Type II
- Type III
- Type IV
- Type V
Collagen Synthesis and Folding Requirements
Synthesis of collagen proteins within the body is a complex process. First, cells must properly read the genes in our DNA to produce the α chains. Three α chains then wrap around each other. Whether or not the α chains are identical depends on the type of collagen [R].
When these single α chains are produced within the cell, enzymes (prolyl hydroxylase and lysyl hydroxylase) modify the amino acids proline and lysine. These modifications are essential for forming a stable triple helix [R].
Each type of collagen has specific ratios of glycine, proline, hydroxyproline, and hydroxylysine. Mutations affecting collagen can have negative health effects.
Genetic Disorders That Decrease Collagen Production
Brittle Bone Disease (Osteogenesis Imperfecta)
Osteogenesis Imperfecta (OI) is a collagen-related disease, which is both heritable and incurable. This is a painful disease characterized by fragile bones and abnormal tissues [R].
Depending on the mutation, an individual might be diagnosed with a mild, severe, or lethal OI condition, yet any form of the condition will increase the individual’s risk of bone fractures [R].
OI is an autosomal dominant disorder, meaning it only takes one of the two genes to be mutated in order to see the effect in the body. A single mutation in the COL1A1 gene can reduce the amount of type I collagen and cause a mild OI disorder [R].
The most common mutation is a substitution of the glycine amino acid in the triplet, which generally causes improper folding of the triple helix. Severe and lethal forms of OI are the result of mutations in either COL1A1 or COL1A2 genes that disrupt the triple helix [R, R, R].
Ehlers-Danlos Syndrome (EDS) is caused by a collagen deficiency or a defective collagen structure. Most commonly, EDS is linked to the mutations of COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, which affects collagens type I, III, and V. These mutations are all affecting fibrillar collagens required in the skin, tendons, and vascular system [R].
Many mechanisms and mutations can reduce collagen production and lead to EDS. There are at least 10 different subtypes of EDS [R].
Generally, all EDS patients share the same features of highly elastic skin, fragile skin, flexible joints, and easy bruising. EDS patients usually have unstable joints and are more prone to dislocations and chronic pain. Some forms of EDS are far more life-threatening, as patients may have an increased risk of rupturing blood vessels [R, R].
Benefits of Collagen Supplementation
1) Collagen Improves Symptoms of Rheumatoid Arthritis and Osteoarthritis
In 60 patients with severe rheumatoid arthritis (RA), three months of chicken type II collagen reduced the number of swollen and tender joints compared to placebo (DB-RCT). Four patients in the collagen group saw all symptoms disappear and a halt in the progression of the disease [R].
A larger study (DB-RCT) of 274 RA patients found that multiple doses (20, 100, 500, and 2,500 μg) reduced swollen and tender joint counts [R].
A study (DB-R) of 52 patients with osteoarthritis found that 90 days of chicken type II collagen reduced symptoms of their conditions, decreased pain, and improved their ability to complete daily activities including walking up and down stairs [R].
In dogs with arthritis, type II collagen for 90 days reduced pain and increased physical activity [R].
2) Collagen Improves Joint Health
A study (DB-RCT) of 147 athletes with joint pain found that collagen hydrolysate for 24 weeks significantly reduced their pain [R].
In another study (DB-RCT) of 139 athletes with knee pain, five grams a day of collagen peptides for 12 weeks reduced activity-related pain [R].
3) Collagen Improves Skin Health
The skin is the largest organ on the body, and collagen is one of its main components. As we age, collagen content decreases by 1% per year (per unit area of skin surface). This decrease can be seen in the form of wrinkling, loosening, and sagging skin [R].
One study in 69 women (DB-RCT) found that daily collagen supplementation for eight weeks increased skin elasticity, an indicator of increased collagen [R].
Another study in 85 women (DB-RCT) found that eight weeks of collagen hydrolysates improved skin moisture, elasticity, wrinkles, and roughness (all signs of increased collagen) [R].
4) Collagen Increases Hair Growth
In a study of 15 women with thinning hair (DB-RCT), 180 days of collagen supplementation resulted in improvements in hair volume, scalp coverage, shine, and thickness. Skin moisture and smoothness also improved [R].
Topical administration of collagen may be beneficial for hair growth, as it can attach and penetrate into the outer layer (cuticle) of hair follicles and increase their thickness [R].
In addition to supplementing with collagen, you can also look for hair and skin care products containing collagen hydrolysate.
5) Collagen May Increase Bone Density
Collagen is also a major component of bones. As we age, collagen production decreases in our bones, which decreases bone density. Individuals over the age of 70 have lower bone density and increased risk of injury [R].
Patients suffering from osteoporosis and porous bone disease lose bone more rapidly than normal [R].
Hydrolyzed collagen increased bone density in rats [R].
Hydrolyzed collagen also increased type I collagen in the bones of rats with osteoporosis [R].
Hydrolyzed collagen stimulates human cartilage-producing cells (chondrocytes) to make more extracellular matrix molecules, including collagen itself. These findings indicate that collagen may effectively prevent age-related bone density reduction in humans [R].
6) Collagen Improves Blood Sugar Regulation
Normal blood sugar levels are between 70-130 mg/dL between meals and no greater than 180 mg/dL two hours after eating [R, R].
7) Collagen Helps Treat Bedsores
In a study (RCT) of 89 patients with bedsores (pressure ulcers), collagen hydrolysate supplementation three times a day for eight weeks improved healing of bedsores [R].
Factors That Decrease Collagen Production
1) UV Radiation Decreases Collagen Production
UV radiation activates several cell growth factors and cytokine receptors, which increases MMP (matrix metalloproteinase) production and decreases collagen type I production [R].
2) Vitamin C Deficiencies Decrease Collagen Production
Vitamin C is required for the proper formation of collagen. Vitamin C deficiency can lead to scurvy. Scurvy is the result of malformed collagen in the ECM. This leads to degraded tissues and may eventually cause death [R, R, R].
3) Smoking Decreases Collagen Production
Smoking tobacco can decrease collagen production. Smokers produce 18% less collagen type I and 22% less collagen type III in their skin than non-smokers [R].
Matrix metalloproteinases (MMPs) are responsible for degrading matrix proteins like collagen. MMP-8 levels 2x greater for smokers than non-smokers, meaning the matrix proteins are degraded at a faster rate [R].
The tissue inhibitor of matrix metalloproteinases (TIMP-1), normally stops MMPs from degrading collagen. TIMP-1 levels are 14% lower in the skin of smokers [R].
It is well known that stress negatively impacts our health. Stress can indirectly lead to accelerated skin aging and poor wound healing by decreasing collagen integrity [R].
5) High Blood Sugar and Diabetes Decreases Bone Quality
Collagen is a long-lived protein (has a low biological turnover). Amino acids in collagen like lysine and hydroxylysyl can accumulate sugars as we age. High blood sugar (hyperglycemia) makes collagen more susceptible to glucose accumulation [R, R].
As we age, collagen becomes stiffer. Researchers can predict a person’s age by how well their collagen is digested in the laboratory. Individuals with diabetes generally show stiffer collagen [R].
Patients with high blood sugar have less enzymatic crosslinks between collagen strands, resulting in less stable collagen formation [R].
Sugars block the LOX enzyme from properly forming collagen [R].
Sugar can also block receptors on collagen. When these receptors are blocked, then this makes them unrecognizable to the receptors. Due to this fact, diabetes can alter collagen-associated cell signaling and gene expression and cause the release of pro-inflammatory molecules and free radicals [R].
How to Increase Collagen Production
1) Nutrients that Increase Collagen Production
Many types of collagen supplements exist, but often times they require multiple doses throughout the day. Here are a few key factors that will stimulate collagen production naturally:
- Vitamin C – is found many fruits and vegetables. It is required for enzymes to hydroxylate collagen and form healthy cross-linked fibrils [R, R].
- Lysine and proline – are found in lean meats like chicken and fish. They are the amino acids required to build stable tropocollagen helices [R].
- Vitamin B3 (niacin) – is also known as niacinamide and nicotinamide. Found in high concentrations in lean meat, peanuts, and mushrooms. It is a precursor to NAD/NADH, which can help stimulate collagen synthesis [R].
- Vitamin A – also known as retinol, is found in liver, eggs, and dairy products. It can reduce the activity of matrix metalloproteinase (MMPs) and increase collagen production [R].
2) Exercise Increases Collagen Production
3) Royal Jelly Increases Collagen Production
Royal Jelly (RJ) is secreted by the glands of honeybees. It contains many proteins, sugars, fats, vitamins, and minerals. RJ also contains unsaturated fatty acids that increase collagen production and decrease collagen degradation (lowers MMP activity) [R].
One study found that rats who were fed a 1% supplement of RJ produced more collagen in their skin [R].
4) Aloe Vera Increases Collagen Production
Aloe Vera is a plant that is widely used in skin and hair products like lotions, ointments, and shampoos. Traditionally, aloe is used for reducing skin irritations like sunburns or other types of chaffing.
Aloe vera supplements can improve wrinkling of the skin by increasing collagen production and decreasing collagen degradation. Patients who used aloe vera for 90 days showed an increase in collagen production and a decrease in MMP-1 gene activity [R].
5) Silicon May Increase Collagen Production
Silicon is a trace nutrient that is likely involved in collagen production.
Silicon increases collagen production and the amount of an enzyme needed to make collagen (prolyl hydroxylase) in cartilage and bone cells [R].
A form of silicon callled orthosilic acid (OSA) increased type 1 collagen production in bone cells [R].
Rats deprived of silicon have decreased collagen production in wounds and bones [R].
OSA increased collagen levels in the skin of calves [R].
A study (DB-RCT) of 134 women with low bone density (osteopenia) low bone density or osteroporosis found that OSA supplementation for 12 months increased markers for type 1 collagen synthesis and bone mineral density in the femus [R].
Another study (DB-RCT) in women with sun-damaged skin found that OSA increased skin smoothness and reduced hair and nail brittleness, indicating increased collagen production [R].
Collagen supplements generally come from cows, pigs, or fish. Most of these supplements are hydrolyzed, meaning that the bonds holding collagen strands together are broken.
Collagen tripeptide, collagen hydrolysate, gelatin, gelatine hydrolysate, and hydrolyzed gelatine are other names for hydrolyzed collagen. Hydrolyzed collagen peptides are smaller than normal collagen structures, which allows the body to absorb and use them.
Gelatin and collagen hydrolysate come from the same sources: skin and bones. There are two main differences between the two collagen supplements.
Firstly, the peptides are much smaller in hydrolyzed collagen than unhydrolyzed gelatin. Unhydrolyzed or partially hydrolyzed gelatins have longer collagen peptides and do not dissolve well in water [R].
Secondly, hydrolyzed collagens are more easily digested and absorbed into the body. Large unhydrolyzed collagen peptides can only bind to the peptide transporter, PEPT1. Small peptides are able to bind with both PEPT1 and PEPT2 transporters, allowing hydrolyzed collagen to be digested and absorbed easier [R, R, R].
Side Effects of Collagen Supplements
User Reviews of Collagen Supplements
Most people who have taken collagen report a good experience. They notice a significant decrease in joint pain, increased flexibility, and faster hair and nail growth. There are few negative experiences. More often than not, the bad reviews are due to a lack of effect rather than side effects.
“It’s interesting that when you look at the most articles about collagen and its health benefits, improving digestion isn’t really mentioned as the first thing. Improving bone and joint health seems to be number one reason for using it, followed by all the anti-aging benefits collagen has. However, for me, the most noticeable change has been much better digestion. I’ve always dealt with some kind of digestive issues, but I’m feeling a lot better now as I’ve added a scoop of collagen peptides into my coffee every day. My husband’s knees used to always get really sore after some time of sitting. After starting to use collagen, which has been about 30 days, according to him his knees feel much better. The pain isn’t completely gone, but there’s much less of it.”
“The first couple of months I took collagen, I could genuinely feel improvements in my janky ankle, almost on a daily basis. At this point, it feels MUCH healthier, almost as healthy as my normal ankle, with a way more normal range of motion. My ROM still isn’t perfect, but there’s way less pain and astoundingly, less swelling.”
“I tried one dose of Marine collagen, supposedly very high quality, to help my nails, hair, and skin. My hormone specialist recommended this therapy. Unfortunately, approximately 15-20 minutes after I ingested it I experienced tingling in my left leg and very rapid heart rate. It scared me to death. I guess it’s not for me. I had complete cardiovascular work up in January. My heart is fine.”
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