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

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

As a research scientist, I have 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 wound healing.

Wound healing is a complex series of reactions that involve at least four distinct processes. These different processes are often referred to as phases, but that implies a sequence of events. While some processes do indeed precede others, some also occur simultaneously.

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

The 4 Stages of Wound Healing

Stage 1: Hemostasis—The first thing your body needs to do when it gets wounded is to stop the bleeding. During hemostasis, blood vessels narrow in order to reduce blood flow. Platelets begin to clump together as a way to patch up the tear in the blood vessel wall. Next, the blood starts to clot as a way of “plugging up” the wound. An enzyme called thrombin activates the formation of a fibrin mesh that covers the platelet plug and helps forms a stable clot. Once the bleeding is under control, inflammatory cells migrate to the site of the wound to begin the inflammation phase of wound healing.

Stage 2: Inflammation—Inflammation plays a key role in initiating the process of healing. It helps to regulate the 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 response, which, under normal conditions, lasts between 4 and 6 days. While inflammation is an essential part of healing, sustained inflammation is counterproductive and slows 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 extracellular matrix formed from connective tissues cells called fibroblasts. The edges of the wound (referred to as the wound margins) contract and pull toward the center of the wound, as new tissues and blood vessels are formed. Cells called epithelial cells move from the wound margins and travel across the wound bed, covering the new tissue. The collagen that is created during this phase, however, is disordered and thick. This process can last as few as 4 days and as many as 24.

Stage 4: Maturation Phase—Starting at around day 21 of the healing process, the maturation phase restructures the collagen from type III to type I so that the collagen lines up with the wound’s tension lines. Collagen creeps ever closer together and cross-links, a process that reduces the thickness of a scar and strengthens the skin growing over the wound. This phase can last over a year, but healed wounds tend to never 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, then successful wound healing can’t occur. A range of factors—from advancing age to inadequate nutrition—can impair the wound healing process. Failure to complete all 4 stages of wound healing successfully can cause pathological inflammation and chronic, non-healing wounds.

Factors that Slow Wound Healing

Wound healing isn’t cut and dry. There are many physiological factors that slow wound healing. 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 not all the contaminants are 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 age 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 process. Interestingly, exercise has demonstrated a protective effect on wound healing in the aging population because it helps reduce levels of pro-inflammatory molecules in wound tissue.

Medications: Certain medications, such as glucocorticoid steroids, non-steroidal anti-inflammatory drugs (NSAIDs), and chemotherapeutic drugs, can prohibit platelet function and clot formation, and exert undesirable anti-inflammatory effects during wound healing.

Inadequate protein/amino acid intake: If you’re not supplying your body with the increased protein intake it needs during wound healing, then collagen synthesis suffers, the wound tissue won’t be as strong, and your 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 times of wound healing.

Diabetes: If a person is insulin resistant, meaning they have a decreased sensitivity to insulin, then wound healing is 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 skin wound healing. (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 so than the sum of the individual effects of each treatment. 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 is a somewhat unique protein, as it is composed of approximately 90% nonessential amino acids.

Nonessential aminos are produced in the body, and therefore you would not expect them to affect how quickly a protein can be produced. It is, therefore, 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 is not responsive to variations in the intake of dietary amino acids, increased amino acid intake does stimulate protein synthesis in wounded skin. Specifically, the essential amino acids (those amino acids not produced in the body) have been shown to stimulate collagen production and speed wound repair.

How do essential amino acids help jumpstart 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 is not responsive to increased intake of dietary amino acids). So, it’s not an availability issue. Rather, the 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 pro-inflammatory cells, the body can make more fibroblasts, which are 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 that produce 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.

Dr. Robert Wolfe

Robert R. Wolfe, PhD, has researched amino acid and protein metabolism for more than 40 years. His work has been continuously funded by the National Institutes of Health since 1975. He has published more than 550 scientific articles and 5 books that have been cited more than 60,000 times according to Google Scholar.

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