Protein Replacement Therapy: A Promising Medical Treatment Approach

Protein replacement therapy is a method for treating diseases and disorders by replacing missing proteins in diseased cells. Clinical trials show it can help to treat rare diseases, like recessive dystrophic epidermolysis bullosa, as well as common conditions such as heart disease. Here’s what you should know about the science behind protein replacement therapy as well as its potential applications.

Most laypeople haven’t heard of protein replacement therapy, but the world of molecular medicine is abuzz with interest in this promising medical treatment. A chief aim for those working in the field of molecular medicine is to develop an efficient way to reliably replace missing proteins in diseased cells. Gene therapy is one possible method for achieving that, but according to the U.S. National Library of Medicine, a database overseen by the National Institutes of Health (NIH), this experimental approach comes with considerable risks and significant advances will need to be made before it becomes safe. Other methods of protein replacement therapy, however, do not require the transfer of genetic material into cells, which eliminates some of the most significant issues that arise with gene therapy while still allowing for the delivery of missing or deficient proteins.

Read on to learn more about protein therapy and its potential treatment applications.

The Science of Protein Replacement Therapy

So far, most of the research into protein replacement therapy has been focused on its use for the treatment of rare monogenic diseases. These conditions occur because of a single defect in a single gene found in human DNA. Though these diseases are considered rare, experts estimate there are over 10,000 of them and that they affect millions of individuals around the globe.

Supporting Research Into Treatments for Rare Diseases

Developing treatments for rare diseases can be quite challenging, in part because companies are less likely to make a profit off such treatments, and therefore less likely to fund research into potential treatments and cures. In an effort to address this, several countries have passed legislation to encourage companies to develop drugs to treat “orphan diseases,” a classification applied to “diseases with a prevalence of less than 200,000 affected individuals in the United States and less than approximately 250,000 affected individuals in the European Union (EU),” per an article titled “Protein Replacement Therapies for Rare Diseases: A Breeze for Regulatory Approval?” that was published in Science Translational Medicine in 2013.

The U.S. Orphan Drug Act, passed in 1983, extends regulatory, commercial, and tax incentives to companies investigating drugs designed to treat orphan diseases. In 2000, the EU passed a similar piece of legislation and multiple other countries have since followed suit. Currently, genetic diseases (along with rare types of cancer and drugs with pediatric indications) rank among the top three in terms of approved orphan drug treatments. And protein replacement therapies for monogenic diseases is a popular subcategory within that realm.

Justifying the Use of Monogenic Protein Replacement Therapies

Blood factors and enzyme replacement therapies for lysosomal storage disorders were two of the first monogenic protein replacement therapies (MPRTs) to receive regulatory approval with orphan drug classification in the United States and EU. When these drugs went to market, manufacturers introduced what’s known as “orphan pricing,” a system in which high premiums are charged to compensate for limited demand. According to the Science Translational Medicine article, the cost of MPRTs, a category that includes drugs like Fabrazyme, Elaprase, and Naglazyme, tops $200,000 annually while sales come in at over $100 million.

Given those numbers, it’s hardly surprising how much attention has been paid to the prices charged for orphan drugs, and, subsequently, the difficulties faced by health care systems when it comes to reimbursement. Determining which patients should be approved for these costly treatments requires complicated calculations, and not everyone agrees on which criteria should be used.

The paradigm so far has been that the use of MPRTs can be reimbursed in the United States, most member countries of the EU, and Japan. It’s also common practice for these drugs to be provided at no cost in countries with low average household income levels and underdeveloped health care systems.

The authors of the Science Translational Medicine article argue that in order to justify the high prices charged for orphan drugs and the rates at which health care systems reimburse for their use, manufacturers must demonstrate that they are, in the long-term, cost-effective treatments. While clinical trials have shown that long-term use of MPRTs can be safe, clinically effective, and lead to health-related improvements in terms of quality of life, more research is needed to conclusively prove that their use leads to net reductions in health care costs.

13 Vital Facts About Protein Replacement Therapy

Potential Applications for Protein Replacement Therapy

Clinical trials have investigated the use of protein replacement therapy for a variety of conditions, including:

Two of the most promising applications to date are for the treatment of recessive dystrophic epidermolysis bullosa and heart failure.

Protein Replacement Therapy for Recessive Dystrophic Epidermolysis Bullosa

Studies conducted on the use of protein replacement therapy to treat recessive dystrophic epidermolysis bullosa have yielded highly promising results.

This disease belongs to the epidermolysis bullosa family, a collection of genetic disorders related to structural proteins in the skin. Individuals with these disorders have atypically fragile skin and mucous membranes that are prone to splitting and blistering. To compound matters, the underlying gene defect compromises wound healing. If wounds do manage to heal, extensive scarring is typical.

Recessive dystrophic epidermolysis bullosa (RDEB), one of the most severe iterations, happens when the gene coding for type VII collagen protein either does not function properly or is absent. This protein helps the two primary layers of the skin—the epidermis and the dermis—adhere to each other. Without it, the skin often separates, leading to blisters and a higher risk of infection.

The NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases highlighted research done with mice that indicated protein replacement therapy could be the key to treating this debilitating genetic condition.

The research, published in Molecular Therapy and the Journal of Investigative Dermatology, examined two techniques for replacing absent or defective type VII collagen with the goal of improving wound healing and reversing both structural and molecular defects in the skin of individuals with RDEB.

The first technique involved topically applying human recombinant type VII collagen (rC7) to the backs of mice with normal collagen genes. After 2 weeks, the team of researchers led by David T. Woodley, M.D., and Mei Chen, Ph.D., of the University of Southern California discovered that the rC7 had been stably incorporated and sped up the skin’s healing process. It also decreased scarring compared to untreated mice. The beneficial effects lasted for 2 months.

Next, the researchers tried topical applications of rC7 on RDEB skin grafts attached to the backs of mice. When rC7 was applied to broken skin, it was successfully incorporated and improved wound healing. However, when it was applied to intact skin, it was not incorporated. The researchers concluded that this limits the use of topical rC7 as it can only help to increase the rate of healing for existing wounds and cannot prevent the formation of wounds or blisters.

The second technique was intravenous administration of rC7. The research team began by wounding the skin on the backs of mice with normal collagen genes and injecting rC7 into their tail veins. They discovered that the rC7 traveled to the wounds where it was successfully incorporated. Again, it appeared to accelerate healing. They found no evidence of rC7 in healthy, wound-free skin or internal organs.

Subsequently, the team examined the effects of administering rC7 intravenously to mice with RDEB skin grafts. The injected rC7 traveled to the skin grafts where it “created new anchoring fibril structures, which hold the epidermis together.”

According to study authors Drs. Woodley and Chen, “Intravenous delivery of rC7 opens up new prospects for more systemic treatment of the disease. Our data suggest that intravenous rC7 not only improves the healing of multiple RDEB-related wounds simultaneously, but it can also prevent new blisters from developing in RDEB skin.”

Protein Replacement Therapy for Heart Failure

While much of the excitement about protein replacement therapy has to do with its use for the treatment of rare genetic disorders, it shows promise as a treatment for more common health conditions too.

Myocardial infarction (heart attack) and heart failure are among the top causes of death in the United States and other countries. A myocardial infarction occurs when blood flow to a segment of heart muscle drops below adequate levels. The greater the length of time before treatment to restore blood flow takes effect, the greater the loss of cardiac muscle cells, or cardiomyocytes. Because the adult heart has little capacity for regeneration, the cardiomyocytes lost in the aftermath of a myocardial infarction get replaced by different types of cells, resulting in scarring and, frequently, heart failure.

To develop an efficacious means of promoting heart regeneration, researchers must find solutions to a multitude of quandaries. It appears that protein replacement therapy utilizing modified mRNA (modRNA) may avoid many common pitfalls. “Modified mRNA (modRNA) is a safe, non-immunogenic, efficient, transient, local, and controlled nucleic acid delivery system,” noted the authors of a 2019 article published in Molecular Therapy.

Increased understanding of the molecular pathways and genes involved in heart disease has led scientists to believe protein replacement therapy could be used to target signaling pathways involved in heart disease progression. Per the Molecular Therapy article cited above, delivering replacement proteins to the myocardium (the muscle tissue of the heart) can encourage the regeneration of cardiomyocytes.

Gene Therapy

Some approaches have fallen into the subcategory of gene therapy, which involves placing a defined gene into a cell to either replace a defective gene or to increase the amount of a certain gene in a specific cell or tissue in order to increase production of a needed protein. Some examples of work in that vein included using viral vectors like adeno-associated virus (AAV) to mediate the delivery of either FGF1 and p38 MAP kinase proteins or periostin.

However, the use of viral vectors comes with the risk of viral genome insertions. While preclinical studies have returned encouraging results, namely, “robust and consistent gene expression,” there has also been evidence of adverse effects, including immune responses to the viral vectors.

Direct Delivery of Proteins

As experts continue probing how best to use gene therapy to treat cardiac disease, a consensus is growing that the most practical way to change the expression of a protein of interest is to deliver the corresponding protein directly to the myocardium. This circumvents problems associated with other delivery methods, such as the potential immune responses triggered by viral vectors. It’s also been linked to benefits such as:

  • Higher levels of protein expression
  • Improved dose regulation
  • Enhanced control

Direct protein comes with some issues of its own, however, including the short half-life and overall instability of injected proteins.

Modified mRNA Therapy

Unlike gene therapy and the direct delivery of proteins, mRNA-based therapies have proven to be highly promising methods of treating heart disease as well as other disorders. One reason for that is its overall safeness, because mRNA does not integrate into the genetic code.

The first successful use of direct mRNA transfer occurred in the late 1980s in mouse models. Then, in 2008, a team of researchers from the Department of Neurosurgery and Department of Medicine at the University of Pennsylvania in Philadelphia, the Laboratory of RNA Molecular Biology at The Rockefeller University in New York, and the Department of Host Defense at the Research Institute for Microbial Diseases in Osaka discovered how mRNA therapy could be used in genetic and regenerative medicine. Essentially, by modifying mRNA with a naturally occurring modified nucleoside pseudouridine to produce modified mRNA (modRNA), researchers changed its structure so that the body was better able to utilize it to address issues related to protein defects or deficits.

According to the authors of the Molecular Therapy article, modRNA “allows rapid, transient, and efficient gene expression to a specific time window after cardiac injury.” They further state that modRNA protein replacement therapy could be “an excellent therapeutic agent to address experimental and clinical needs to induce cardiac regeneration and promote cardiac function in ischemic heart disease.”

Key Takeaways About Protein Replacement Therapy

Protein replacement therapy offers a way to treat diseases by transporting missing or deficient proteins to cells, thereby correcting the dysfunction that results in disease. Other techniques for doing this involve transferring genetic material into cells, which comes with a higher level of risk.

At this time, one of the most pertinent applications for protein replacement therapy is as a treatment for rare monogenic diseases, which fall into a category called “orphan diseases” because manufacturers are less likely to develop drugs to treat them due to the limited financial incentive for doing so. While some experts view protein replacement therapy as a much-needed option in a realm with a dearth of viable potential treatments, others feel manufacturers still need to do more work to show that using these treatments ends up being a cost-effective decision for health care systems.

It’s important to note, too, that the promise of protein replacement therapy is not limited to rare diseases. Clinical trials have shown it can also be used to overcome one of the central challenges of treating myocardial infarction and preventing heart failure.

As researchers continue to explore applications for protein replacement therapy, it seems likely that they’ll uncover an even broader swathe of diseases and conditions it can be used to treat.

How to Speed up Healing: From Sunburns to Surgery Recovery

The wound healing process, much like our physical activity levels, tends to decline as we age. Here are some scientifically backed tips on the best ways to speed up healing, from minor cuts and scrapes around the home, to post-surgical recovery and muscle tissue rebuilding.

Whether you have a cut, a burn, or are healing from a surgical procedure, there are ways to help speed up healing and close your wounds faster. The wound healing process, much like our physical activity levels, tends to decline as we age. The older we get, the longer our healing time takes, leading in some instances to chronic wounds that never really go away. To speed up wound repair, here are some tips for helping your body along.

Speed up healing: from sunburns to surgery.

At-Home Healing: Small Wounds and Scar Reduction

When it comes to home remedies for wound care, there are a lot of old wives’ tales still around. Some of them make a certain amount of sense when considered scientifically, like waiting 30 minutes to swim after you eat may well help you avoid a minor cramp. However, not all of these folktales are true enough to keep repeating or insisting on. Not everyone will get a minor cramp if they swim after eating, and even if they do, it won’t cause them to drown. And yet still we wait, and tell children to wait, and keep the myth going.

When it comes to how to speed up wound healing, there are a lot of practices that don’t really apply. Some say leaving a wound open to dry in the air and “breathe” helps it heal faster, but that isn’t true if it’s now open to dirt and possible infection. To stop infection, many douse a wound in alcohol or peroxide—talk about pouring salt on a wound!

In truth, leaving a wound to dry out is not ideal, and can even slow healing and increase pain. Wounds need moisture to heal, and moist wound healing speeds up healing and reduces scarring. Here are some other tips on how to foster faster healing and reduce the risk of scarring.

1. Clean and Disinfect

Before touching a wound, wash your hands. When it comes to cleaning the wound, start with clear water and a clean cloth to remove any dirt or particles from the wound. If there are pieces of debris in a wound (your kid took a wipeout on their skateboard and has gravel embedded in the scrape, for example), use a pair of tweezers to remove them. The tweezers should be sterilized with some isopropyl alcohol, but alcohol is not advised directly on the open wound.

Instead, once the wound is clean, apply an antibiotic cream, ointment, or spray to the wound area, and make your call about what kind of bandage applies. If it’s an open wound like a wide scrape, a gauze and a wrap may be called for, but a cut on a finger might need only a bandaid to reduce the risk of infection and speed healing.

Remember not to pick at any scab that forms, because a scab is the body’s natural bandage.

2. Encourage Blood Flow

Nobody can heal you better than your own body, but there are ways to help it along. You’ll notice when you get a scrape or a bruise that the area seems to heat up. That’s because the body has dispatched its in-house medical team via your bloodstream.

To increase blood flow to the skin and surrounding area, you can apply a heating pad or hot water bottle, or place the wound area in some warm water for 15-30 minutes. It’s not a high-tech method but it does help, especially for wounds on your extremities (fingers, toes, arms, and legs) where your blood vessels are smaller, or for anyone with poor circulation, like the elderly.

If adding heat is uncomfortable, massaging the surrounding area is another way to usher blood to the site of injury.

3. Reduce Inflammation

After encouraging healthy blood flow, your wound may experience unhealthy inflammation. A burn that you got from pulling dinner out of the oven might feel like it’s still burning for days after, and you’ll want some kind of anti-inflammatory to help relieve the pain.

Many people think of the gel-like insides of the aloe vera plant for burns, and this is an age-old home remedy that actually works! Aloe vera is a succulent plant originally native to Africa that has a gooey substance in its leaves called mucilaginous juice, and while the plant is 99% water, it does have two chemicals within that improve wound healing.

According to researchers, many of the healing effects of aloe vera are due to the glycoproteins and polysaccharides present in the plant’s pulp. The polysaccharides increase cellular movement, leading to faster tissue regrowth, and the glycoproteins help relieve pain and control the inflammatory response. Together these compounds aid and possibly improve your immune system.

There is even more evidence out of a 2015 study that suggests there are further helpful compounds in aloe vera for cutaneous wounds (like sunburns). For instance, glucomannan stimulates the growth of fibroblasts responsible for collagen, skin cell, and tissue building. Other chemicals found in aloe vera may also help foster blood vessel regrowth, making it a fantastic, natural anti-inflammatory to have on hand for minor wound healing.

4. Get More Protein, Vitamins, and Nutrients

There are certain power foods that contain the nutrients your body needs to rebuild itself, including vitamin C, vitamin D, vitamin E, omega-3 fatty acids, and magnesium. You’ll find these nutrients in dark green leafy vegetables and in orange, yellow, and red fruits and veggies (eat the rainbow!), like bell peppers, tomatoes, oranges, and more.

One of the biggest factors when it comes to tissue and wound healing though? Protein. Omega-3s come from fish along with fish’s protein content, and you can get an assortment of your essential amino acids from various meats and dairy products.

Amino acids are needed for wound healing, so if you’re not a meat-eater, you can increase your protein intake with certain vegetarian and vegan protein foods, or with an amino acid supplement while you heal.

How to Speed up Healing After Surgery

Outside of household and playground injuries, recovery after surgery is a whole different ball game. No matter where it is on the body or how good the chances for a speedy recovery are, surgery still carries a certain amount of risk, and so does surgical recovery. Once you’re sent home from your procedure, you’re going to want to heal as quickly and safely as possible. Here are some tips for how to do so.

1. Follow Your Doctor’s Instructions

While it’s true that no one knows your body quite like you do, doctors don’t give out suggestions willy-nilly. Their medical advice is based on data and research collected from all different kinds of patients over years and years of procedures.

If a doctor tells you to avoid activities for a specific amount of time after a procedure, it’s in your best interest to heed that advice. If you’re told to avoid driving, avoid sexual intercourse, avoid alcohol, or avoid lifting anything over 10 pounds for a couple of weeks, this is for your safety, and so you don’t end up back in their office with a new injury or complication. You may be feeling good enough to return to normal activity, and that’s great, it means your healing is right on course! And yet there may still be healing processes going on beneath your skin that need a little bit more time.

2. Eat the Right Recovery Foods

As true as it was for minor wounds, eating a nutrient-dense diet is even more important after a surgery, because you’re healing much deeper wounds. Although you may have a loss of appetite or digestive discomfort after a surgery, it’s important that you eat a healthy diet by any means necessary (broths, smoothies, amino acid powders), because certain foods are actually going to feed your recovery process.

Again, vitamin C and zinc can help with healing, and can be had from fruit and beans. Iron and vitamin B12 help in forming new blood cells and can be found in fish and eggs. Sports and sugary drinks should be avoided for the time being, as should refined sugar foods.

Protein is more important than ever, as many surgeries by nature involve cutting through tissue and muscle, and the amino acids in protein can help speed post-surgical recovery. Meat, poultry, fish, and eggs are all strong sources of protein, but if a doctor tells you to take a protein supplement, look for a comprehensive amino acid supplement. For recovering after surgery, you may need more protein than a normal diet or your appetite can provide, and supplementing may be a necessity.

3. Follow-up, Ask For Help, and Get Moving Gradually

Surgical recovery may take a while and involve follow-up appointments, physical therapy, and/or at-home assistance. During this time, it’s important to keep all appointments with your health care team, because a diagnostic such as bloodwork could alert your doctor to a problem before it becomes an infection. Likewise, physical therapy could help you correct something like a limp before it becomes a misalignment.

Asking for help from your family or your medical team may not be your usual tendency, but it is necessary and encouraged for the sake of a speedy and successful recovery. If problems are allowed to fester, you could end up back in the hospital or on bedrest, and in danger of new problems altogether, like muscle atrophy.

4. Don’t Smoke

This is a tip that may not apply to all, so if you don’t smoke or have never smoked, skip ahead. However, if you are a smoker or live with one, the effects of cigarette smoking can counteract your wound healing.

Nicotine tightens blood vessels, and the more constricted your blood vessels are, the harder it is for all the other recovery work you’re doing to matter. The nutrients you eat won’t be going to the right places, the muscle you’re building takes longer to thrive, your wounds take longer to heal, and more carcinogens and harmful substances are coming in at the same time. If you’ve ever wanted to quit smoking, after a surgery it’s more important than ever, and can make even more of a positive health impact.

The Need for Speed

Some things can’t be rushed, and a lot of the time your health is the tortoise racing against the hare: slow and steady wins the race. Diet and exercise are long-haul habits that make all the difference. While that’s also true when it comes to a lot of aspects of healing, the more you can do to support your body’s healing mechanisms and get out of their way, the faster the process goes and the lower the chance you’ll have any more problems arising from the initial issue.

Whether it’s a cut, a sunburn, a broken limb, or a surgical operation, anything can go from bad to worse if you’re not careful. Luckily there are resources you can use and advice to be had on how to speed up healing in a successful and sustainable way. Take these tips into consideration, seek medical advice if needed, and know that we wish you a speedy recovery.

Serrapeptase: The Science Behind the Supplement

Mostly used by health care professionals in Japan and Europe for reducing inflammation after trauma, surgery, or in other inflammatory circumstances, serrapeptase is also available as a dietary supplement for its various health benefits. Find out what serrapeptase is, how it was discovered, and which of its supposed benefits have the strongest evidence backing them.

Serrapeptase, also known as serratiopeptidase, serratia peptidase, or silk worm enzyme, is an isolated enzyme from bacteria found in silk worms. Mostly used by health care professionals in Japan and Europe for reducing inflammation after trauma, surgery, or in other inflammatory circumstances, it is also available as a dietary supplement for its various health benefits. This article will explore the science behind those health claims, discuss the potential side effects of serrapeptase, and help you decide whether this anti-inflammatory is right for you.

What Is Serrapeptase?

The serrapeptase enzyme is a proteolytic enzyme, which means it has the ability to break down proteins into their building blocks, amino acids. It’s an enzyme produced by the bacteria living in the silk worm’s digestive tract, and specifically it’s the enzyme that allows an emerging moth to dissolve and digest its own cocoon. If you’re the kind of person who finds bugs and worms to be skin-crawlingly gross, it might do you well to think less about where this enzyme comes from, and more about what it and other proteolytic enzymes like bromelain, chymotrypsin, and trypsin can do to benefit you.

Discovered throughout the 1950s, these enzymes were used in the United States to relieve the inflammation caused by ulcerative colitis, rheumatoid arthritis, and post-surgical swelling. By 1957, the Japanese were using serrapeptase in the same manner, and in the 1990s these different enzymes were compared and it was found that serrapeptase was the most successful at reducing inflammatory responses. Since then it has become more widely used in Europe and Japan for its anti-inflammatory benefits.

The Benefits of Serrapeptase

Though serrapeptase is relatively new to the medicinal scene, there have nevertheless been many studies done to document its effectiveness and safety. Here are some of the benefits that have been observed from the use of serrapeptase.

Serrapeptase supplements: the science and the speculation.

May Reduce Inflammation

This is the health benefit serrapeptase is best known for, reducing inflammation in instances like tooth removal or post-surgery recovery. It’s thought that serrapeptase works by decreasing inflammatory cells at the site of injury. The anti-inflammatory effects of serrapeptase were shown in a clinical trial on the surgical removal of wisdom teeth, and serrapeptase was found to be more effective at improving lockjaw than more powerful drugs like ibuprofen and corticosteroids.

Though corticosteroids improved facial swelling more effectively on the first day post-surgery, the differences on the second day were insignificant. While more research is still needed to define the best uses of serrapeptase going forward, the researchers in the study did note that serrapeptase had a better safety profile than the other drugs analyzed, which may make it particularly useful in cases of drug intolerance in patients, or those who have adverse side effects with stronger drugs.

May Prevent Infections

There is evidence that serrapeptase may decrease the risk of bacterial infection by acting as a “biofilm buster,” so-called because bacteria have the ability to join together and form a protective barrier or film around themselves. The biofilm shields them from antibiotics long enough that their rapid growth can take place and cause infection. Serrapeptase can inhibit the formation of biofilms, increasing the efficacy of antibiotics in cases like Staphylococcus aureus (Staph. aureus), or staph infection, one of the most common opportunistic dangers associated with hospital stays.

Both animal and test-tube studies have shown that serrapeptase combined with antibiotics was more effective than treating Staph. aureus with antibiotics alone, including those strains that have become drug-resistant. An example of a drug-resistant form of staph infection is MRSA (methicillin resistant Staph. aureus), an especially dangerous infection to those who are already hospitalized in immune-compromised states.

May Reduce Pain

Pain being a symptom of inflammation, serrapeptase has been known to reduce pain by inhibiting certain compounds. For example, in one double-blind study that examined the effects of serrapeptase in about 200 people with inflammatory conditions of the ear, nose, and throat, researchers found that those who took a serrapeptase supplement had significant reductions in mucus production and pain severity than did those who took a placebo.

Another study found that serrapeptase reduced pain significantly compared to a placebo in 24 participants following the removal of their wisdom teeth. More research is needed for scientists to be sure of serrapeptase’s effects, but these findings show promise for those hoping to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) after medical procedures.

May Help Dissolve Blood Clots

It is thought that by acting to break down fibrin (a protein formed in blood clots) as well as damaged and dead tissue, the serrapeptase enzyme could help treat atherosclerosis. Atherosclerosis involves plaque buildup inside your arteries, which leads to a hardening and narrowing of the arteries and an increased danger from blood clots.

If serrapeptase is successful at dissolving plaque or blood clots, it could reduce a person’s risk of stroke or heart attack. However, not enough studies have been done showing a direct effect, and so while there is potential that serrapeptase has a role in treating blood clots, more research is warranted.

May Be an Aid Against Chronic Respiratory Disease

Chronic respiratory and chronic airway diseases affect the lungs and breathing apparatuses of the body. Serrapeptase’s potential to clear mucus and reduce inflammation in the the lungs could help improve breathing in those with asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension, which is a form of high blood pressure in the vessels of your lungs.

These chronic conditions are ongoing and incurable, and yet managing the symptoms effectively (as with increased mucus clearance and better dilation of air passages) can greatly improve a person’s quality of life. One month-long study of 29 participants with chronic bronchitis involved a test group that was given 30 milligrams of serrapeptase per day, which resulted in less mucus production than the control group, better lung-clearing ability, and greater ease of breathing.

May Treat Endometriosis

Due to the potential serrapeptase has for targeting dead tissue and scar tissue throughout the body, some believe there is potential in using serrapeptase for endometriosis treatment. Endometriosis occurs when endometrial cells grow outside the uterus, in the tissues surrounding the pelvic area, causing pain and often issues with fertility.

Likewise with conception issues arising due to ovarian or uterine cysts, serrapeptase for fertility is another natural therapy that currently has more anecdotal evidence than scientific research done on it, though that does not mean the research won’t be done, nor that it wouldn’t be a safe supplement to try in consultation with a qualified health care professional.

May Help Relieve Alzheimer’s Disease

One study on rat models revealed that the proteolytic enzymes nattokinase and serrapeptase may have a therapeutic application in the treatment of Alzheimer’s disease, modulating the different factors that characterize the disease. Oral application of these enzymes provided a decrease in transforming growth factor, acetylcholinesterase activity, and interleukin-6, all of which are found in high levels among patients with Alzheimer’s disease. While more research still needs to be done, Alzheimer’s is a medical condition that needs any relief options available.

Potential Serrapeptase Side Effects

Because it’s such a new commodity, people are rightly concerned that there could be potential serrapeptase dangers. There are not many published studies touching on potential adverse reactions to taking serrapeptase, however some studies have reported the following side effects.

As there is a lack of data on the long-term safety and tolerability of this enzyme, should any side effect occur after you take it, you should stop immediately and seek medical advice. What works for some may not work for all, and so your judgement is paramount when it comes to whether you’re getting the benefits you want.

How to Take Serrapeptase

It’s advised against taking serrapeptase with any sort of blood thinner, or other dietary supplements like turmeric, garlic, or fish oil which could increase a risk of bruising or bleeding. For serrapeptase dosage, it’s recommended to take between 10-60 milligrams per day (the range used within the various studies) on an empty stomach, and to avoid eating for at least 30 minutes afterwards.

When purchasing the supplement, choose a product in an enteric-coated capsule to prevent your stomach acid from neutralizing the enzyme before it reaches your intestine. Without a strong enough capsule, the enzymatic activity could be deactivated before it has a chance to work.

How long does it take serrapeptase to work after you take it? For pain and swelling it can have immediate effects post-surgery, but for more gradual or ongoing treatments, the effects might be felt over a period of weeks. It truly depends on your condition, your health, and how you’re using the supplement.

The Secrets of Serrapeptase

Our understanding of serrapeptase is far from comprehensive at this moment. There is one study linking it to treatment of carpal tunnel syndrome and anecdotal evidence suggesting serrapeptase for weight loss (albeit temporary). There are far more clinical studies on the use of serrapeptase for reducing inflammation, fighting infections, and preventing blood clots, but researchers are still exploring its uses. Should you be interested in seeing what serrapeptase supplementation can do for you, we only ask that you do so wisely, and with a willingness to consult a medical professional about any results you find, be they bad or good.

Treating Bee Stings: How to Take the Sting Out

What do you do when a bee strikes with its stinger? We’ll take a look at what you should do for treating bee stings and some helpful remedies to take the sting out!

You hear the buzz, and then…ouch! You’ve been stung by a bee. For most people, bee stings cause a mild reaction and are just a temporary nuisance, but a sting from these flying insects can still pack a punch. What do you do when you’re stung by a bee and what remedies provide relief from the itching and pain? We’ll take a look at what you should do for treating bee stings and taking the sting out!

Why Bees Sting

Bees are not out looking to find someone or something to sting. The stinger is strictly used when the bee believes its colony is under attack or its life is in danger. Both wasps and bees will sting when a person or animal comes near their nest or hive. The risk of becoming stung increases if you are using something that causes a loud noise, such as a lawn mower, or if you swat or shout at a bee, or wear bright-colored clothes. Multiple bees may also pursue you after the single bee sting if the species contains pheromones in the bee’s venom, which alerts the rest of the hive to attack.

Sting Reactions

Bee and wasp stings are fairly common, especially during the warmer months when people are outside for longer periods of time. The initial sting can be unpleasant and lead to throbbing and pain at the sting site but typically does not cause any severe reactions. The pain from a bee or wasp sting is caused by your body’s reaction to the toxin that is released from the insect’s stinger.

Your immune system kicks into action, with white blood cells arriving first on the scene to rid the body of the antigens in the bee venom. Soon after you are stung, your body releases serotonin and histamine that cause an allergic reaction at the sting site. As your body continues its fight, the site becomes inflamed and swollen and may be painful and hot to the touch. You can often spot a small white dot in the middle of the sting site where the stinger went into your skin. For most people, the swelling and pain subside within hours of being stung, especially if it is not on an area that is ultra sensitive, like the face, ears, or neck.

Bee vs. Wasp Stings

The main reason bees only sting as a last resort is that they have barbed stingers that are torn off upon contact and they will die soon after stinging. If they believe it’s a matter of life or death for their hive or themselves, they will go into attack mode. You may notice you must remove the stinger or venom sac after being stung, since it is often left behind after the bee flies away.

Like bees, wasps have a stinger that contains venom but their stingers do not have barbs and usually retract upon stinging. Since the stinger remains intact, a wasp, as well as other stinging insects like hornets and yellow jacket wasps, can sting you multiple times.

Allergic Reactions

For most people, when an insect stings it’s just a nuisance, but for others, it can be serious and have life-threatening complications. Some individuals will experience substantial swelling or redness at the sting site due to a more serious reaction. For those who are highly allergic, a bee or wasp sting can turn into a life-threatening situation quickly. A bee or wasp allergy can cause anaphylaxis (wheezing and difficulty breathing), rapid heartbeat, hives, low blood pressure, swelling of the throat or tongue, and dizziness or fainting. In incidences of anaphylactic shock, emergency medical care is needed to counteract the severe allergic reaction.

What do you do when you’re stung by a bee and what remedies provide relief from the itching and pain? We’ll take a look at what you should do for treating bee stings and some helpful remedies to take the sting out!

Bee Sting Treatments

Unless you have a bee sting allergy, most bee and wasp stings can be treated at home with over-the-counter products or home remedies.

If you’re stung by a bee, gently extract the stinger using your nails or the firm edge of a credit card. Avoid using tweezers, which can drive more toxic venom into the wound. Toxins can still be released from the bee’s stinger if left in place so prompt removal is important.

Using soap and water, wash the area well and apply an astringent or antiseptic with a cotton ball. Next grab an ice pack, ice cube, or cold compress and hold over the sting site to calm inflammation. For additional treatment of bee and wasp stings, you can find several products at your local drugstore or gather a few items around your house to alleviate the pain and provide bee sting itch relief.

Over-the-Counter Treatments

  • Oral antihistamine: Benadryl or Claritin can help relieve the swelling and itching that accompanies a bee sting.
  • Tylenol: To relieve pain and swelling, take ibuprofen or acetaminophen as directed.
  • Hydrocortisone cream: An over-the-counter cream like 1% hydrocortisone cream can be applied topically to curb itching and calm irritation.
  • Calamine lotion: Used to treat many skin rashes, bug bites, and irritations, calamine lotion can relieve itching and help to dry up the site quickly.

Home Remedies

  • Honey: It’s a bit ironic that honey can soothe a bee sting, but it is very effective at helping the wound heal and relieving the pain and itching. Spread honey over the wound and cover with a loose bandage; leave on for up to an hour and then rinse.
  • Apple cider vinegar: To help neutralize the toxin in the bee sting, apply an apple cider vinegar compress to the sting site and let sit for several minutes.
  • Toothpaste: To soothe the burn that can follow a bee sting, apply a squirt of white toothpaste to the wound and let dry.
  • Meat tenderizer: Papain, an enzyme in meat tenderizer, appears to cause the protein responsible for itching and pain to break down. Apply a mixture of 1:4 meat tenderizer to water and leave on the sting site for half an hour.
  • Baking soda: A baking soda paste made with water is a traditional anti-itch remedy for everything from bee stings to mosquito bites. Cover with a bandage for 15 minutes.
  • Aspirin paste: A topical paste made from an aspirin tablet and water is helpful for reducing pain.
  • Tea tree oil: A natural antiseptic, tea tree oil can help ease bee or wasp sting pain. Add a few drops to coconut oil and apply to the irritated area.
  • Ammonia: Effective at breaking down the protein in bee venom, ammonia can offer quick relief and help reduce swelling.
  • Aloe vera: From relieving sunburns to skin irritations, aloe vera can help soothe a bee sting. Slice a leaf from the aloe plant to extract the gel or buy pure aloe from the store and apply to the sting site.
  • Witch hazel: When witch hazel is used to treat a sting, it can relieve itching, pain, and inflammation.
  • Activated charcoal: Charcoal should be in everyone’s first aid kit since this age-old remedy can immediately provide pain and swelling relief. Found in health food stores, the contents of charcoal capsules can be mixed with water to form a paste. Spread the paste over the sting site and gently cover. Repeat this throughout the day until symptoms are relieved.

Preventing Bee Stings

If you know you’ll be spending time outdoors, take these steps to reduce your risk of a bee sting:

  • If bees fly near you or begin to swarm around you, this is a warning. Slowly and calmly leave the area without swatting or swinging your arms.
  • If you kick or knock into a hive or nest, immediately run away as quickly as possible. If you can get to an enclosed area, do so.
  • Avoid going outside barefoot.
  • Do not wear bright colors such as yellow or red.
  • Do not disturb a hive if you come across one.
  • Keep food and soda covered during picnics.
  • Drive with windows up.
  • Avoid open garbage cans.
  • If you have been prescribed an epinephrine auto-injector (an EpiPen), always have two with you at all times.

Bee stings can be painful, whether you’re allergic to bees or not. If a bee or wasp stings you or someone you know, try to remain calm and get to a place where you can treat the sting as soon as possible to lessen the effects and speed up relief.

5 Proven Health Benefits of Amino Acids

Amino acid supplements are popular in the bodybuilding world. But amino acids, while key muscle makers, perform many more health-enhancing feats. They can help improve mood, keep stress at bay, and even strengthen the immune system. Let’s take a look at 5 of the most celebrated benefits of amino acids.

Amino acids, fittingly nicknamed the building blocks of proteins, not only make up the protein you eat, but also join together to form proteins in your body. These proteins are the very foundation of your hair, nails, bones, muscles, cartilage, connective tissues, and skin. They are the proteins your body uses to build and repair tissues and to synthesize hormones and enzymes. When you eat dietary protein, your body breaks amino acids into their individual parts, and then uses these amino acids to build the protein your body requires. Given that amino acids are so integrated into the makeup of the human body, it’s hardly surprising that researchers have uncovered a plethora of health benefits of amino acids.

Amino acids play a key role in muscle health, and, for this reason, amino acid supplements are popular in the bodybuilding world. But amino acids, while key muscle makers, perform many more health-enhancing feats. While they undoubtedly play vital roles in processes such as muscle growth and muscle recovery, they also contribute to brain function. Research indicates that increasing your amino acid intake from food sources or by taking supplements can help improve mood and keep stress at bay. Plus, they can strengthen the immune system. Before diving deep into five scientifically validated health benefits of amino acids, let’s take a moment to go over some amino acid basics.

The Basics of Amino Acids

In scientific terms, amino acids can be defined as organic compounds composed of nitrogen, carbon, hydrogen, and oxygen, along with a variable side chain group. Scientists have identified 20 different amino acids that the human body requires in order to properly develop and maintain itself. Though all 20 make essential contributions to your overall health, 9 of those amino acids have been categorized as essential amino acids (EAAs):

  1. Histidine
  2. Isoleucine
  3. Leucine
  4. Lysine
  5. Methionine
  6. Phenylalanine
  7. Threonine
  8. Tryptophan
  9. Valine

The reason scientists deemed those nine amino acids essential is that your body cannot independently produce them, making it essential that you obtain them from the food you eat or supplements you take.

Three of the nine essential amino acids exist in their own subcategory: the branched-chain amino acids (BCAAs). Those amino acids are:

  1. Isoleucine
  2. Leucine
  3. Valine

While many have touted the benefits of BCAA supplements, based on the impressive effects of those three specific amino acids, the truth is that to benefit from an increased supply of one amino acid, your body must have a balanced amount of all the essential amino acids.

The 11 amino acids necessary for human health that the body can produce on its own are called nonessential amino acids (NEAAs), because it’s not essential that you consume them.

However, the dividing line between essential amino acids and nonessential amino acids has more wiggle room than their names might initially lead you to believe. Enter the conditionally essential amino acids. Of the 11 nonessential amino acids, 7 have been identified as conditionally essential:

  1. Arginine
  2. Cysteine
  3. Glutamine
  4. Glycine
  5. Proline
  6. Serine
  7. Tyrosine

While your body has the ability to generate these amino acids, that ability becomes compromised under certain conditions, like if you become ill or are dealing with chronic stress. To illustrate this idea, let’s look at how this plays out with one specific conditionally essential amino acid: arginine. Researchers have found that your body cannot produce enough arginine on its own while fighting diseases such as cancer. Under those conditions, it becomes essential to augment your body’s supply of naturally produced arginine with supplemental arginine.

Now that you have a working understanding of the different types of amino acids relevant to human health, we can discuss some of the most exciting, research-backed health benefits associated with individual amino acids.

5 Proven Benefits of Amino Acids for Your Body and Mind

We rely on amino acids to perform a multitude of roles. An adequate intake of amino acids helps us build muscle, maintain mental focus, maximize exercise performance, and more. Amino acids contribute to crucial bodily functions such as:

  • Protein synthesis
  • Tissue growth and repair
  • Energy production
  • Immune defenses
  • Wound healing
  • Nutrient absorption

Individual amino acids have been shown to prevent muscle loss, increase energy, boost endurance and stamina, improve mood, decrease body fat percentage, speed recovery time, enhance immune health, optimize sleep quality, and more.

The essential amino acids, which your body cannot generate, can be found in high-quality sources of dietary protein. While eating a vegetarian or vegan diet may necessitate that you pay closer attention to your amino acid intake, it’s certainly possible to meet your body’s needs using only plant-based proteins. Furthermore, it can be beneficial to take concentrated doses in supplemental forms regardless of how healthy and balanced a diet you eat.

Essential amino acids are the only macronutrients required for survival. A normal diet containing high-quality proteins should deliver adequate amounts of essential amino acids to meet minimal requirements. However, amino acid supplements can provide benefits not achievable with even high-quality protein food sources.

Amino Acid Benefit #1: Muscle Protector

Muscle tissue consists mainly of proteins, and protein is made of amino acids. It stands to reason that amino acids would have a pronounced effect on muscle growth. As you may be aware, increasing your amino acid intake can boost muscle mass, strength, and function by stimulating muscle protein synthesis, or the building of new muscle tissue.

Did you know, however, that amino acids also help prevent muscle breakdown during exercise or between meals? In other words, they not only encourage muscle growth, but they also protect the gains you’ve worked so hard to build.

When you exercise, your body uses glucose, fats, and protein as fuel sources. If the body is low in fuel, it will start pulling protein from muscles, chipping away at your overall muscle mass. For instance, endurance activities quickly drain your stores of branched-chain amino acids (BCAAs). To avoid muscle loss, it’s important to supply your body with more essential amino acids, either by eating dietary protein or supplementing with amino acids. This ensures amino acid levels in your bloodstream stay stable and keeps your muscles protected.

Amino Acid Benefit #2: Energy Generator

As I touched on above, your body requires fuel to carry out tasks such as contracting your muscles. However, the body stores very little energy. The energy stored in your muscle takes the form of creatine phosphate.

Three amino acids—arginine, methionine, and glycine—join together to form creatine. The process of breaking down creatine phosphate releases energy that can provide an immediate source of fuel for muscle contraction. It gives us the energy boost we need for activities like sprinting or lifting heavy weights.

Because only a small quantity of creatine phosphate can be stored in our muscles at any given time, we depend on a different kind of cellular energy called adenosine triphosphate (typically abbreviated to ATP) for more sustained exercise activities. As with creatine phosphate, the breakdown of ATP provides energy that can fuel muscle contraction. When ATP is broken down, it forms adenosine diphosphate (ADP). Your body then regenerates ATP from ADP and phosphate in small organelles in the muscle called mitochondria.

There are a number of proteins in the mitochondria that enable the production of ATP from the oxidation of glucose, fatty acids, and amino acids. These specialized proteins are called enzymes. The more mitochondrial enzymes you have, the more ATP can be produced and the more energy is available to fuel muscle function. The number of mitochondrial enzymes depend on the number of mitochondria and the number of oxidative enzymes in each mitochondria.

Amino acids play a crucial role in increasing both the number of mitochondria available to generate ATP as well as the number of enzymes within each mitochondria. Both the formation of new mitochondria and the enzymes they contain result from protein synthesis.

A proportionately blended amino acid supplement stimulates the production of new mitochondria and increases the number of enzymes in the mitochondria by stimulating mitochondrial protein synthesis. Thus, an ample availability of dietary amino acids is an indispensable part of producing the energy our bodies need to keep functioning and to perform at their best.

Amino Acid Benefit #3: Endurance Enhancer

In addition to increasing your body’s ability to produce physical energy to fuel exercise performance, amino acids can help improve mental energy during a long workout.

Your mental energy depends on the balance between the inhibitory neurotransmitter serotonin (which brings on feelings of calm) and the excitatory neurotransmitter dopamine (which stimulates feelings of excitement). These neurotransmitters are made inside the brain from amino acids circulating in your bloodstream. The amino acid tryptophan serves as a precursor to serotonin production and tyrosine fulfills the same role for dopamine.

During long, grueling workouts, the balance between tryptophan uptake and tyrosine uptake can be disrupted. The brain begins to let in more tryptophan, and as production of serotonin outstrips production of dopamine, you end up feeling mental fatigue. You have plenty of physical energy to keep going, but not the cognitive drive you need.

Taking an amino acid supplement with a balance of essential amino acids can counter the increased uptake of tryptophan by the brain, helping you work out for longer by reducing serotonin production and thus delaying the mental perception of fatigue.

It is important to use an appropriately balanced amino acid mixture that also increases dopamine production, as it is the balance between serotonin and dopamine that determines your mental energy level.

As I briefly mentioned earlier when introducing the concept of branched-chain amino acids, taking an imbalanced mixture of amino acids will not yield the results you hope for. While taking a BCAA supplement can reduce the uptake of tryptophan by the brain, it will also reduce the amount of tyrosine taken up by the brain.

In order to boost mental energy so you can sustain focus during a workout, an amino acid supplement must decrease the ratio of serotonin to dopamine in the brain. Decreasing the amount of serotonin will have minimal effect on brain focus and energy if the amount of dopamine is also reduced. It is, therefore, important that you use a balanced amino acid supplement that not only decreases brain tryptophan uptake, but also increases the dopamine precursor tyrosine.

Amino Acid Benefit #4: Mood Stabilizer

As we just discussed, too much serotonin can cause fatigue during workouts. Too little serotonin, however, has been linked to depression, anxiety, insomnia, and overall moodiness. While tryptophan, and subsequently serotonin production, is ideally down-regulated during exercise, it can have a palliative effect when it is increased in individuals battling mood disorders.

Low tryptophan can be especially problematic when you are dieting. Dieting generally calls for eating fewer calories, which typically entails eating less protein, even if you’re on a so-called high protein diet. So, it is especially important to consume sufficient tryptophan if you’re on a diet.

There are two other standout amino acids for promoting balanced moods. The first, which I introduced in the preceding section, is tyrosine. This amino acid functions as a precursor not only for dopamine, but also for the equally influential brain chemicals epinephrine and norepinephrine. Increasing your intake of tyrosine has been shown to significantly amplify energy, strengthen motivation, elevate sexual function, and heighten concentration, thereby benefiting mood. The best route to increasing tyrosine levels, however, is not to up your intake of tyrosine itself but rather to focus on the essential amino acid phenylalanine, which the body then converts into tyrosine.

The third amino acid that’s particularly important when it comes to promoting balanced moods is glutamate. This nonessential amino acid can act as a neurotransmitter itself, but is probably more relevant as a mood enhancer due to its role as the precursor of gamma-aminobutyric acid, better known as GABA. As the main inhibitory neurotransmitter in the brain, GABA helps us feel calm and relaxed and prevents overstimulation of nerve cells. Glutamate is produced from glutamine, so both glutamine and glutamate have similar effects on GABA production.

It’s also worth noting that theanine, a non-dietary amino acid, mimics some of the properties of glutamate and GABA. Green tea is one of the few natural source of theanine, and probably responsible for green tea’s reputation as a mood enhancer.

Amino Acids Benefit #5: Immune Strengthener

Nutritional deficiencies, stress, and environmental toxins can take a toll on our immune systems. Amino acid support can help keep our immune systems strong.

People with compromised immune systems tend to have low levels of the amino acid cysteine, which is a precursor of the master antioxidant glutathione. To efficiently and effectively increase your stores of this vital amino acid, select a balanced essential amino acid supplement that contains cysteine in the form of N-Acetyl-L-Cysteine (NAC).

Research consistently demonstrates that an increased intake of cysteine can fortify the immune system. According to one study published in The European Respiratory Journal, supplementing with cysteine significantly decreased flu symptoms in elderly patients.

Since cysteine is produced from the essential amino acid methionine, it’s also possible to use methionine supplementation to achieve similar effects while promoting the production of proteins involved in the immune response.

Lysine is another amino acid noted for its antiviral and immune-boosting properties. It is traditionally recommended as a preventative nutraceutical for flare-ups of the herpes virus and shingles.

If only one piece of information from this article stays with you, I hope that it is this: in order to benefit from the properties of any individual amino acid, it is vital that you supply your body with an appropriate quantity of all the essential amino acids. That’s why research consistently shows that the most reliable way to access the health benefits of amino acids is by taking a carefully formulated essential amino acid supplement.

The 4 Stages of Wound Healing: How Amino Acids Can Accelerate Wound Repair

Wound healing is a complex series of reactions that involve at least four distinct processes. Let’s first take a look at what happens when you get a wound and the 4 stages of wound healing so that we can better understand how proper nutrition and amino acids can accelerate wound repair.

As a research scientist, I’ve conducted many studies on wound healing and nutritional and metabolic support following serious illness and/or injury. Throughout my 40-year career, amino acid nutrition has emerged as a major nutritive aid for the four stages of wound healing.

These four distinct stages involve a complex series of reactions often referred to as the phases of wound healing. But that implies a sequence of events. While some processes do indeed precede others, some also occur simultaneously.

Let’s take a look at what happens when you get a wound so that we can better understand how proper nutrition and essential amino acid support can accelerate the healing process.

The 4 Stages of Wound Healing

Stage 1: Hemostasis Phase

The first thing your body needs to do when it gets a wound is to stop the bleeding. During the process of hemostasis, blood vessels narrow in order to reduce blood flow, and platelets begin to clump together in order to patch up the tear in the blood vessel wall.

Next, the blood starts to clot as a way of “plugging up” the wound, and an enzyme called thrombin activates the formation of a fibrin mesh (composed of a type of insoluble protein) that covers the platelet plug and helps form a stable clot.

Once blood loss is under control, inflammatory cells migrate to the site of the wound to begin the inflammatory phase of wound healing.

Stage 2: Inflammatory Phase

Inflammation plays a key role in initiating the process of healing. During this second phase, inflammation helps to regulate bleeding and protect against infection by removing debris, bacteria, and pathogens from the wound site.

Inflammatory agents—white blood cells, nutrients, enzymes, and growth factors—create the redness, swelling, and pain typically associated with the inflammatory phase, which, under normal conditions, lasts between 4 and 6 days.

While inflammation is an essential part of the healing process, sustained inflammation is counterproductive and actually slows healing.

4 stages of wound healing

Stage 3: Proliferative Phase

During this tissue growth phase, the wound is filled and covered using new tissue made of collagen (the protein that gives skin its strength and structure) and an extracellular matrix formed from connective tissue cells called fibroblasts. The wound edges (referred to as wound margins) contract and pull toward the center of the wound as new blood vessels and tissues are formed.

During the initial stage of this process, the new tissue that is formed is known as granulation tissue. Healthy granulation tissue can be recognized by its pink or red color and somewhat shiny appearance.

Cells called epithelial cells then move from the wound margins and travel across the wound bed, covering the new tissue. This process can last from as few as 4 days to as many as 24. The collagen that is created during this phase, however, is disordered and thick.

Stage 4: Maturation Phase

Starting at around day 21 of the healing process, the maturation phase—or remodeling phase, as it’s sometimes called—restructures the collagen from type III (the main component of reticular fibers, which act as a supportive mesh) to type I (the most common type of collagen in the body and a major structural component of the skin) so that the collagen lines up with the wound’s tension lines.

As tissue repair continues, collagen creeps ever closer together and cross-links (a process that reduces the thickness of the scar tissue and strengthens the skin growing over the wound). This phase can last more than a year, but healed wounds tend never to regain 100% of their tensile strength (the ability to resist tension and not break).

If one or more of these phases is disrupted or incomplete, successful wound closure can’t occur. A range of factors—from advancing age to inadequate nutrition—can impair the wound healing process. And failure to complete all four stages of wound healing successfully can cause a pathologic inflammatory response and chronic, non-healing wounds.

Factors That Slow Wound Healing

Wound healing isn’t cut and dried. In fact, there are many physiologic factors that can slow this complex process. For example, according to a scientific article published in the Journal of Dental Research, the rate of wound healing can be slowed by:

  • Infection
  • Aging
  • Medications
  • Poor overall health
  • Inadequate nutrition
  • Insufficient tissue oxygenation
  • Age and sex hormones
  • Diabetes
  • Stress
  • Obesity
  • Alcoholism
  • Smoking

Let’s discuss a few of these factors in more detail.

Infection and Chronic Inflammation

Inflammation is crucial during wound healing because it clears the wound of bacteria and toxins that can cause infection. If all contaminants are not cleared from the wound site, then pro-inflammatory molecules remain elevated indefinitely, the immune system becomes compromised, and the wound becomes vulnerable to infection.

Advancing Age

Between 3 and 6 million people in the United States suffer from chronic wounds. And 85% of them are aged 65 or older. Advancing age is a primary risk factor for impaired wound healing because age-related characteristics affect every phase of wound healing and can delay the entire process.

Interestingly, exercise has demonstrated a protective effect on wound healing in the aging population, as it helps reduce levels of pro-inflammatory molecules in wound tissue.


Certain medications, such as glucocorticoids (a class of steroids), non-steroidal anti-inflammatory drugs (NSAIDs), and chemotherapeutic drugs, can interfere with platelet function and clot formation and exert undesirable anti-inflammatory effects during wound healing.

Inadequate Protein/Amino Acid Intake

During wound healing, the body needs an increased supply of protein to keep up with the demands of collagen formation. However, if you’re not supplying your body with the increased protein intake it needs during this process, collagen synthesis suffers, wound tissue isn’t as strong, and the wound is more vulnerable to infection.

With regard to nutritional status, inadequate nitrogen intake in the form of amino acids or dietary protein also impairs wound healing. For this reason, adequate amino acid nutrition is crucial during this process.


If a person is insulin resistant, meaning they have a decreased sensitivity to insulin, wound healing will be impaired. Such is the case for people with diabetes, a chronic disease marked by insulin resistance. Older people may also fall prey to insulin resistance and impaired wound healing.

My research team and I discovered that a local insulin-zinc injection can accelerate the wound healing process. (You can read about the study here.) However, without extra amino acids, an increase in insulin has only a modest effect on the net gain of protein in the wound. Insulin helps prime the cells’ response to extra dietary amino acids by increasing the rate of protein synthesis.

The stimulatory effect of the combination of increases in amino acids and insulin stimulates wound healing more than the sum of the individual effects of each treatment. In other words, supportive amino acid nutrition can work with insulin to help build protein and accelerate wound repair.

Amino Acids and Wound Repair

How fast a wound heals depends on how fast proteins can be built. The synthesis of all the proteins in new cells is important, but the most crucial component of wound repair is the synthesis of collagen.

Collagen is the primary protein component of the connective tissue that rebuilds the wound. It’s a somewhat unique protein as well, as it’s composed of approximately 90% nonessential amino acids.

Nonessential amino acids are produced by the body, and you’d not expect them to affect how quickly a protein can be produced. Thus, it’s not surprising that increasing the amount of amino acids you take—as a supplement or by eating more dietary protein—has little effect on how quickly normal skin makes protein.

Although protein synthesis in normal skin does not respond to variations in dietary amino acid intake, increased amino acid intake does stimulate protein synthesis in wounded skin. Specifically, the essential amino acids (those amino acids not produced by the body) have been shown to stimulate collagen production and speed wound repair.

How do essential amino acids help jump-start collagen production in wounds?

Because collagen is composed of less than 10% essential amino acids, there are most likely enough available to stimulate collagen protein building (that’s why collagen synthesis in normal skin isn’t responsive to increased intake of dietary amino acids).

So, it’s not an availability issue. Rather, essential amino acids help regulate the inflammatory process—and not just during stage 2 of wound healing, but throughout all phases.

Essential amino acids decrease the number of inflammatory cells that are activated during the entire process of wound healing. By decreasing these pro-inflammatory cells, the body can make more fibroblasts—the cells that produce collagen during the proliferative stage of wound healing. The result is the faster formation of a dense network of collagen fibers, which produces a stronger wound.

Taking a properly balanced essential amino acid blend optimized for targeted wound healing support can help protect against an overactive immune response and increase the amount and quality of new collagen, for faster and more durable wound healing.

Should You Take an Ornithine Supplement for Muscle Building?

Visit any bodybuilding forum on the web and you’ll see mention of ornithine and its athletic performance-enhancing and muscle-building benefits. But is an ornithine supplement the best amino acid supplement for muscle building?

Visit any bodybuilding forum on the web and you’ll see mention of ornithine and its athletic performance-enhancing and muscle-building benefits. This amino acid (also called: L-Ornithine, L-Ornithine HCl, L-Ornithine Hydrochloride, L-5-aminorvaline, L-2,5-diaminovaleric acid, and Ornithine HCl) is frequently promoted as a dietary supplement for stimulating muscle growth. But is an ornithine supplement the best amino acid supplement for muscle building?

5 Top Uses for Ornithine Supplements

While much of the excitement about ornithine has to do with its impact on muscle mass and athletic performance, scientists have found that this potent amino acid can affect your health in other ways as well.

Here’s further information on five of the top reasons people try ornithine supplementation:

  1. Anti-fatigue effects: Some evidence indicates that ornithine helps flush fatigue-inducing metabolites from your muscles and can relieve fatigue related to excess ammonia in the blood (common with chronic stress).
  2. Increased muscle mass: Studies show that ornithine supplementation can positively influence factors that stimulate the growth of muscle tissue, like testosterone and growth hormone levels.
  3. Boosted athletic performance: Because of its role in the urea cycle, ornithine can increase your capacity for physical exertion, allowing you to push yourself harder, for longer.
  4. Enhanced wound healing: Research shows that ornithine supplementation can substantially improve wound healing, largely due to the way ornithine influences collagen synthesis.
  5. Strengthened immune function: At least one study (which looked specifically at the use of ornithine alpha-ketoglutarate) has found that ornithine can improve your immune function.

How the Body Uses Ornithine

In order to understand the mechanics of L-ornithine supplementation, it’s important to have a grasp on the basics of how your body uses amino acids.

Amino acids, in technical terms, are simple organic compounds that link together to form protein. Our bodies need an adequate supply of amino acids to build muscle tissue and perform other vital functions. Because amino acids—including L-ornithine—are so essential to our overall health and well-being, they’ve earned the moniker: the building blocks of life.

A quick note about why you’ll sometimes see amino acids like ornithine referred to interchangeably as “L-ornithine” and “ornithine.” Amino acids can be in either a D configuration (like D-aspartic acid) or L configuration (like L-aspartate). However, since there really isn’t a “D-ornithine” in supplements, it’s common to see both terms used synonymously.

When we talk about amino acids, we tend to focus on the role they play in protein metabolism. But certain amino acids carry out different functions that are not directly linked to the synthesis or production of protein. These acids are categorized as non-proteinogenic amino acids or NPAAs.

Neither the proteins we eat nor the proteins our bodies make contain ornithine. Rather, ornithine functions in the liver as part of the urea cycle. In fact, the urea cycle is often called the ornithine cycle because ornithine is such an important component.

Understanding the Urea Cycle

The urea cycle is a biochemical reaction that converts ammonia to urea that the body can then excrete. This is an absolutely crucial detoxification process since excess ammonia, a waste product generated from cellular metabolism, can be toxic when blood concentration levels rise too high.

The urea cycle has four phases: 1) your liver produces urea, 2) your liver releases the urea into your bloodstream, 3) the urea travels to your kidneys, 4) your kidneys excrete the urea in your urine.

As part of the urea cycle, ornithine combines with ammonia to form the amino acid L-citrulline, or more simply, citrulline. Citrulline then combines with another ammonia molecule to form the amino acid L-arginine, which is more commonly referred to as (you guessed it) just plain arginine. From here, arginine is converted to ornithine, with urea as a byproduct—and we’re back to where the cycle started. Ornithine to citrulline to arginine to ornithine, and so on.

So, the urea cycle converts ammonia to nontoxic urea for excretion by the kidneys without disrupting amounts of the essential components: arginine, ornithine, and citrulline. In almost all circumstances other than liver failure, the cycle functions adequately to produce urea and prevent excess ammonia from entering the bloodstream. None of the amino acids involved in the urea cycle are essential amino acids, which must be taken in from the food you eat or from dietary supplements. Under normal conditions, the body produces sufficient amounts of these nonessential amino acids to effectively keep plasma ammonia levels in check and produce urea for elimination.

Why You Should Care About Your Nitric Oxide Levels

The idea behind ornithine supplementation (and prior to that, arginine supplementation), is that it can increase blood levels of nitric oxide, a desirable outcome for several reasons.

During the urea cycle, a small percent of arginine is not converted to ornithine but rather is converted to citrulline. Nitric oxide (NO) is the byproduct of this arginine to citrulline conversion. Testing has revealed that nitric oxide helps to regulate how much blood can pass through your blood vessels. When nitric oxide levels increase, the diameter of your blood vessels expands, a process known as vasodilation. Maximizing vasodilation during exercise can be highly beneficial since you want as much blood flowing to your muscle tissue as possible in order to bring in oxygen and nutrients and clear out waste products.

Nitric oxide also supports healthy sexual function in men.

Methods for Increasing Nitric Oxide Levels

As scientists began to appreciate the physiological importance of nitric oxide, they devised different approaches to promote its production.

1. Arginine Supplementation

One of the first methods they tried was arginine supplements, which have been used since the 1950s. In the early days, arginine supplements were considered to have nutraceutical properties, as they seemed to have more potent effects than would have been expected, but the precise mechanisms were not understood.

Subsequent studies showed that the benefit of arginine supplementation was due at least in part to the increased production of NO. Arginine was also found to have a direct stimulatory effect on muscle protein production by activating a key molecular factor inside the cell (mTOR). Finally, in large doses arginine was discovered to stimulate the release of growth hormone.

There are, however, two considerable problems with arginine supplementation. The first has to do with the cellular metabolism of arginine. After L-arginine is absorbed from the intestine it must pass through the liver before reaching the blood in the rest of the body. However, your liver cells very effectively take up and metabolize orally ingested arginine. As a result, consuming oral L-arginine has only a small effect on blood levels of arginine.

The second problem, which is related to the first, is that in order to elevate blood levels of arginine to the desired extent, you have to take doses that are so high they cause digestive distress in most people. Studies show that doses of arginine at 10 grams and higher can cause diarrhea as well as other unpleasant side effects.

2. Ornithine Supplementation

Given the problems with using dietary supplements of arginine, scientists started to explore alternate options for raising arginine levels in the blood with the ultimate goal of increasing nitric oxide production.

We’ve already seen how ornithine, citrulline, and arginine convert from one to the other via the urea cycle. Both amino acids are possible alternative approaches to arginine supplementation. The idea behind ornithine supplementation is to increase arginine by conversion in the urea cycle.

Research indicates that oral L-ornithine supplementation can have an anti-fatigue effect while improving measures of athletic performance including speed, strength, and power.

A study published in the Journal of Sports Medicine and Physical Fitness found that ornithine supplementation increased lean muscle mass as well as power output for weight lifters.

Separate findings from a study done with bodybuilders demonstrated that ornithine can increase growth hormone levels. Low-dose ornithine supplementation had no effect, but the highest dose (170 milligrams of ornithine hydrochloride) increased growth hormone concentrations to 318% above baseline. As with arginine, high doses of ornithine frequently cause digestive side effects.

The effects of ornithine on growth hormone appear to be short-lived. The desirable effects of raising growth hormone levels, such as increased lean muscle mass gains and fat loss, occur when you sustain elevated levels. This makes ornithine supplementation an ineffective method for pursuing those goals.

3. Citrulline Supplementation

Another reason taking an ornithine supplement may not be the most logical route to achieving goals like improved endurance and increased muscle mass is that the ornithine you take is converted to citrulline, which is then converted to arginine. So, ornithine is two metabolic steps away from arginine.

Keep in mind too that if your primary reason for trying arginine supplementation or ornithine supplementation is to build muscle and maximize your athletic performance, you need to increase nitric oxide production and stimulate muscle protein synthesis and muscle growth.

Citrulline is the optimal nutritional supplement to achieve this. Unlike arginine, the liver lets most of the absorbed citrulline pass through. Citrulline is largely converted to arginine in the kidneys, which release the arginine into the blood for circulation to the rest of the body, including muscle tissue. This explains the surprising fact that the blood level of arginine increases much more after consumption of citrulline than after the same amount of arginine.

The second aspect of citrulline that makes it a great way to increase arginine concentration is that citrulline consumption rarely causes gastric distress.

All in all, it appears that supplementing with citrulline is the most effective way to increase blood levels of arginine as well as ornithine, elevate production of nitric oxide, and reap the benefits.