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07th June 2024

Clinical White Paper - WoundVite for Dogs: The Healing Process and Beneficial Nutritional Supplements

Dr. Devan Patel, PharmD
Clinical White Paper - WoundVite for Dogs: The Healing Process and Beneficial Nutritional Supplements

Brittany Sinclair, BVSc(hons), DACVECC, Devan Patel, PharmD

 

Introduction 

Wound care management is an ever-changing field in veterinary medicine.1 It has changed significantly over the past 25 years which can be attributed to understanding more of the cellular process of wound healing as well as the myriad of wound care products and supplements available. Appropriate patient wound care must take into account the normal process of wound healing, patient factors, and comorbidities.2  

While there are many types of dog wounds, from surgical incisions to puncture wounds to traumatic degloving injuries, they all undergo the same healing process. Wound healing generally progresses through four healing stages for any wound including inflammatory, debridement, repair, and maturation phases.  

Inflammation - starts immediately 
Debridement - starts in a couple of hours 
Repair - starts in a couple of days 
Maturation - starts in two to three weeks 

Understanding the process of wound healing, the differences between species, and common factors that can impede it is imperative to successfully manage wounds in dogs. 1,2,3 

 

The Wound Healing Process 

A thorough understanding of the phases of wound healing is a necessity as treatment and additional nutrition can be tailored to benefit certain phases. 

Inflammation is the (dog or human) body’s natural instinct after sustaining an injury. Injured tissues send chemical signals to initiate the healing process.1,2 Capillaries leading away from the injured area are signaled to constrict and the arterioles are signaled to dilate. This results in an increase in blood flow as well as allowing white blood cells and fluids to pass through the injured area. Swelling is a common symptom of inflammation due to the fluids having a higher protein concentration, attracting water to the injured area.1 Other symptoms of inflammation include pain, redness, heat, and immobility. Depending on the severity of the wound and the health of the dog, inflammation can last up to a week.

Debridement is a critical component of wound healing that involves the removal of necrotic tissue and debris from the wound.4 It can occur naturally or it can be manually debrided. Natural debridement and sloughing of dying tissue keep pace with the normal wound-healing process with less severe wounds in healthier dogs. However, necrotic tissue or debris present in the wound bed can hinder wound healing as it affects the migration and multiplication of cells. Not removing this can further delay wound healing by prolonging inflammation secondary to excessive production of proinflammatory cytokines.5 Additionally, the inhibition of developing new, healthy tissue can make the wound site more susceptible to bacterial contamination and infection, allowing it to spread further into deeper tissues.

Forms of debridement include: 

Autolytic – This is painless and favorable for long-term healing. Typically uses dressings to promote moist wound healing. The wound dressing provides a moisture-balanced environment that allows natural enzymes to liquefy the hardened, damaged tissue.1,3

Surgical – This is more aggressive and is performed in an operating room. The veterinarian removes devitalized tissue from the wound bed leaving healthy tissue intact.4

Mechanical – This is a less acceptable form of debridement because it can slow, or halt the regular healing cycle as well as it being generally painful. It is achieved through wet-to-dry dressings or hydrotherapy. 

The repair stage begins to mend the wound. In an uninfected wound, cells begin to grow and rebuild missing and devitalized tissue. New tissue is created by using collagen and a unique cell matrix which is the scaffolding for new tissue to grow. Once this scaffolding is created, the wound undergoes a process where it is filled, connecting the edges closer together and covering the wound area with more cells.6

Maturation is the final stage of healing. During the repair phase, plenty of collagen is deposited at the site of injury. After serving its purpose, the excess collagen appears disorganized, thick, and lumpy. The maturation phase cells that had been used to repair the wound are no longer needed and undergo apoptosis (programmed cell death). Collagen is aligned along tension lines and water is reabsorbed so the collagen fibers can lie closer together and cross-link collagen fibers. This reduces scar thickness and makes the skin area of the wound stronger. However, healed wound areas continue to be weaker than uninjured skin. 2,3,4,5,6 

 

The Variations in Wound Healing Between Species 

Although it is suspected that dogs and cats heal in similar phases and patterns as humans, the final result of healing may be deviated from.7  There is a variety of research on wound healing in animals due to animals being used for translational models for wound healing in humans. These models have been shown to alter genetics, accelerate healing, and are used to obtain tissue samples for testing and analysis. For example, rats heal mainly by contraction of the wound bed while pigs heal mainly by re-epithelization.1  

The differences between dogs and cats have been reported as well. Differences include patterns of granulation tissue formation and decreased cutaneous perfusion, decreased tissue contraction, reduced granulation tissue production and epithelialization, and weaker healed tissue in cats. These differences can be attributed to dogs producing more of an early inflammation response and the differences between cutaneous angiosomes. The vasculature that supplies the cutaneous tissues is composed of subdermal plexus. This is supplied by direct cutaneous vessels. Because a dog typically has greater density and more vessels, they will have a variation in wound healing different than humans.7 

 

Factors That Can Affect Wound Healing 

Some factors affect wound healing and can be divided into three different categories: physical, endogenous, and exogenous factors.8 

Physical factors that affect wound healing include temperature, pressure, and tissue oxygen levels. Temperature can affect the tensile strength of wounds. Ideal conditions to allow wound healing occur at 30°C or 86°F. Pressure can decrease the oxygen levels in the tissues by compromising the blood flow healing area. Vessels can tear from shear forces, also compromising the blood flow. Anything that interferes with blood flow will slow the wound healing process due to the fact that having adequate oxygen levels is essential for proper healing. Not having enough oxygen flowing through the body and wound can interfere with protein synthesis and fibroblast activity, resulting in a delay. Aside from pressure and force compromising oxygen levels, other factors such as overly tight bandages, hematomas, low blood volume, and devitalized tissue are some of those additional factors. 

Endogenous factors include malnutrition and obesity. These factors reflect the overall health of a dog. A dog that is anemic can experience delayed wound healing  from decreased oxygen levels. A dog that has uremia can have delayed wound healing through slowing down  with the process of tissue degranulation formation which can result in producing poor quality collagen.  Nutrition is essential for overall health and the healing effects of the body. Because wound healing is a function of protein synthesis, malnutrition can alter the healing process. The ideal nutritional level for wound healing is unknown, but based on studies, it was shown that low blood protein levels delay wound healing when the total serum protein content is < 2 g/dL. Malnutrition can be in the form of obesity. The metabolic needs of fat cells are different and their ability to mobilize nutrients is diminished. Furthermore, obesity can decrease blood supply as well as cause the sutures to hold onto the subcutaneous fat layers instead of the connective tissue.

Exogenous factors include any external chemical or treatment such as medications or radiation. Corticosteroids are commonly used after surgery. However, steroids can inhibit capillary budding, fibroblast proliferation, and rate of epithelialization. Not having enough or too many vitamins and minerals can affect the healing process as well. Vitamin C is a prerequisite for the hydroxylation of the amino acids, proline and lysine. Zinc is required for epithelial and fibroblastic proliferation, but too much zinc can delay wound healing through inhibition of macrophage function. Radiation and alkylating agents can delay wound healing as well. Inappropriate concentrations of antiseptics can also be another factor. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to delay wound healing in human medicine.

 

Nutrition and Wound Healing  

Delays in wound healing can be caused by a multitude of reasons, such as infection, wound location, certain medications, and underlying metabolic diseases. But, perhaps the most crucial factor is poor nutritional status. Adequate nutrition is one of the most underappreciated facets of wound healing in both dogs and humans.1,2 Healing requires the body to have sufficient energy stores, in the form of fats and carbohydrates, to help rebuild tissue. The body begins to break down endogenous protein in an attempt to meet its needs for the “building blocks” of healing without these resources. Nutritional support is therefore critical for animals with healing wounds. With wound management being an ever-changing field in veterinary medicine, nutritional support should be a strategy implemented in every wound patient. 

 

Fundamental Nutrients to Support Wound Healing 

Vitamin A  

Vitamin A is essential for life in all vertebrate animals.9  Vitamin A is a fat-soluble vitamin that acts as a powerful antioxidant. Vitamin A plays an important role in a dog’s reproduction, embryological development, cellular differentiation, growth, immunity, and vision.10  

There are two primary forms of vitamin A: Active vitamin A (also called retinol) and provitamin A carotenoids, the most important of which is β-carotene. Retinol comes from animal-derived foods and is a type of “pre-formed” vitamin A that can be used directly by the dog’s body. β-carotene is found in plant-based products, which is a precursor molecule since it needs to first be converted to retinol in order to be utilized by the body.11, 12, 13  Because dogs are considered carnivores, β-carotene from plants is limited in their circulation. Dogs have been found to have no to moderate concentrations of β-carotene in circulation when consuming unsupplemented omnivorous diets that likely contain some carotenoids. Another aspect to note is that dogs have colorless fat, so it appears that they do not accumulate β-carotene in their adipose. 

Vitamin A helps regulate the growth and differentiation of many cell types within the skin, and their deficiency leads to metaplasia, epithelial differentiation, abnormal epithelial keratinization as well as compromised function of both innate and adaptive immunity. 

During the wound healing process, vitamin A has shown to have a beneficial impact. Due to its anti-inflammatory properties, vitamin A may be useful in the management of wound care in dogs. Vitamin A increases the inflammatory response in wounds via enhanced lysosomal membrane ability, increased macrophage influx, and activation and stimulation of collagen synthesis. Vitamin A increases the number of monocytes and macrophages at the wound site early in the inflammatory phase, facilitating epithelial cell differentiation. It increases collagen cross-linking and wound-breaking strength. 14,15 

Overall, vitamin A supplementation may accelerate wound healing and surgical recovery and might be even more beneficial in dogs due to the lack of β-carotene.

 

Glucosamine HCl 

Osteoarthritis (OA) is common in humans and dogs. It is characterized by a change in tissues of synovial joints, leading to deterioration of articular cartilage.16 Common findings include hypertrophy of bone at the margins, degeneration of the cartilage, and changes in the synovial membranes. The causes of OA in dogs include trauma, genetic predisposition, and excessive exercise. Risk factors include the breed, gender, animal size, and if they are overweight. Unfortunately, OA can cause chronic pain and disability and cannot be cured. The main goal is to reduce chronic pain improving the patient’s wellbeing. Nonsteroidal anti-inflammatory drugs (NSAIDs) are common drugs that veterinarians may prescribe. However, side effects have been reported. Side effects include changes in appetite, upset bowel movements (diarrhea, bloody stool), behavior changes (activity level, aggression, incoordination), seizures, drinking habits (more or less water consumed), urine changes (color, frequency, smell), lethargy, and skin conditions.  

Dietary supplements and traditional herbal products are increasingly being used for the treatment of pain in dogs. Glucosamine is a chondroprotective agent that is naturally found in joint cartilage and synovial fluid, which lubricates the joints and facilitates easy movement. Glucosamine helps maintain these structures by stimulating the production of glycosaminoglycan (GAG) molecules, which are essential to forming new cartilage and maintaining the structure of mature cartilage. Glucosamine helps keep chondrocytes healthy while also providing anti-inflammatory effects. It stimulates synoviocytes to make hyaluronic acid which is vital in maintaining healthy joints. Glucosamine has minor adverse effects which may include allergies (specifically among those who are allergic to shellfish), insomnia and fatigue at high doses, excessive thirst, and frequent urination.16-19  

In a study, an orally administered glucosamine hydrochloride and chondroitin sulfate combination for the treatment of OA showed statistically significant improvements in scores for pain, weight-bearing abilities, and severity of OA by day 70 (P<0.001) as compared to carprofen, a common NSAID used in canines. Another study investigated the effects of a dietary supplement containing a mixture of Boswellia serrata, chlorophyll, green tea extract, glucosamine, chondroitin sulfate, and hyaluronic acid in dogs. The study concluded that no adverse effects occurred, making the supplement safe and tolerable. It also was shown to be beneficial in reducing pain and in alleviating symptoms of osteoarthritis over a period of 6 weeks.  

Glucosamine continues to be commonly recommended by veterinarians as an alternative for treating osteoarthritis in dogs who are unable to tolerate the adverse effects of NSAIDs, or as add-on therapy. With its anti-inflammatory effects, regenerating factors, the ability to keep chondrocytes healthy, and stimulating synoviocytes to form hyaluronic acid, this suggests that glucosamine may aid in wound healing and the pain associated with it.16-19 

 

Omega-3 (EPA and DHA) 

Omega-3 is a term used to describe a certain set of essential fatty acids. EPA (Eicosapentaenoic acid) and DHA (Docosahexaenoic acid) are the most notable substances. 20 These essential fatty acids are abundantly found in fish including certain cold-water fish, salmon, mackerel, halibut, and herring, or oils made from them. Omega-3 can also be found in krill oil and in products made from algae. The other Omega-3 fatty acid is ALA (alpha-linolenic acid) which is typically found in dark-leafed plants. While both are needed for optimum health, each works differently in the body. 21

Omega-3 is essential in the diet of dogs and cats, as recognized in the nutrient recommendations for pet food provided by the National Research Council (NRC) and the Association of American Feed Control Officials (AAFCO).22 The resolution of inflammation is an active process involving endogenous mediators derived specifically from EPA and DHA, which results in a reduced inflammatory response with decreased platelet aggregation and immunologic stimulation. Endogenous mediators are resolvins and protectins that form in the resolution phase of the inflammatory response and serve to stop inflammation and reduce leukocyte-mediated tissue injury.  

EPA and DHA contribute to healthy skin structure as part of cell membranes.23  When physical or chemical injury to the skin occurs, the omega-3 fatty acids in the damaged cell membranes are converted into compounds that are less pro-inflammatory (resolvins and protectins) and can reduce allergic skin conditions or inflammation. 

A study investigated the effects of fish oil on pruritic skin disease in dogs. Sixteen dogs with idiopathic pruritus, confirmed atopy, or flea allergy were evaluated and received 180 mg of EPA and 120 mg of DHA per 4.55 kg or a control. The dogs that received the DHA and EPA had significant improvements in pruritus (P < 0.02), self-trauma, and coat character (P < 0.001) over time.24 Another study compared dogs with OA receiving a daily supplementation with either mineral oil or fish oil for 3 months. The study outcomes measured pain, lameness, and joint disease in dogs with osteoarthritis for 3 months. The study concluded that daily supplementation of fish oil had consistent clinical improvements in their pain, dysfunction, and overall well-being.25

Omega-3 is commonly recommended by veterinarians as it has been shown to reduce inflammation, promote a silky coat, reduce itchy and flaky skin, and can even help relieve pain, making it an essential supplementation for dogs recovering from a wound or a procedure.20-25 

 

Bovine Collagen 

Collagen, an abundant and important extracellular matrix protein, is the main structural protein found in the skin, tendon, and bone.26  In dogs, it makes up 70% of their skin and coat and 30% of their hips and joints, making it a vital protein in a dog’s body. Dogs, like humans, reduce their capacity to produce collagen over time. This makes them more susceptible to injuries, painful conditions of the bones and joints, poor skin and coat health, and when injured – they take a longer time to heal. Lost collagen might be replaced through supplementation to some extent.  

Collagen supplements originate from various sources such as marine, bovine, and porcine, which can improve skin integrity and modulate skin aging in dogs. Bovine collagen is derived from the bones, hides, and cartilage of cattle and is especially useful for skin, bone, joint, and leaky gut health.  

 

Green-Lipped Mussel Powder 

The green-lipped mussel (Perna canaliculus) are shellfish native to New Zealand.27 Green-lipped mussels possess an exceptional degree of biological activity. Green-lipped mussels contain a high level of omega-3 and other fatty acids, as well as other naturally occurring compounds that may improve joint lubrication, reduce inflammation, stiffness, joint pain, and improve mobility and range of motion. It is notably high in protein, an essential macronutrient in wound healing, accounting for a protein efficiency ratio of 3.6.28 It also contains glycosaminoglycans (ranging from 11-12% by weight) that provide nutritional support to the body, especially the joints. This component has the ability to limit additional deterioration and possibly regenerate damaged joint cartilage and synovial fluid.

Another component that is in green-lipped mussels is eicosatetraenoic acid (ETA).27 This has been shown to provide equivalent pain relief to non-steroidal anti-inflammatory drugs (NSAIDs). This works by blocking the enzyme, cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors. These enzymes trigger the production of prostaglandins and other chemicals that cause inflammation in the body. With the enzymes inhibited, this blocks the formation of damaging prostaglandins and other inflammatory chemicals. There may also be the benefit of protecting the stomach lining and liver from harm.27-28

 

Organic Hemp Seed Powder

Hemp seed comes from the hemp plant, Cannabis sativa, but only contains insignificant amounts of THC.29 Hemp seeds are recognized as a superfood, containing a precise 3:1 ratio of omega-6 to omega-3 fatty acids, high in iron, magnesium, calcium, zinc, and high amounts of fiber.

The mix of omega-3 and omega-6 essential fatty acids gives hemp seeds anti-inflammatory properties.30 This mixture can provide a balance of inflammation, omega-6 may contribute to inflammation, while omega-3 may have an anti-inflammatory effect. This can provide an equilibrium to keep the body balanced when dealing with inflammation. These fatty acids can also support the brain and nervous system, which are partly made up of fats. An additional benefit is that these fatty acids may provide a shinier coat and nourished skin. 

Hemp seeds are high in zinc, magnesium, iron, and calcium, among other minerals, giving the nutrients needed to boost a dog’s immune system.31 The fiber content can also aid a healthy digestive tract, correlating back to a better immune system since the majority of the immune system is in the gut. The mineral magnesium plays a role in body functions that affect mood. It can help relax muscles and keep a dog calm and content during the recovery process after surgery. 

Hemp seed is a nutritional powerhouse containing fatty acids, minerals, and fiber necessary for immunity, mood, and even a shinier coat. This superfood could be a beneficial supplement for surgery recovery for dogs.29-31

 

Organic Turmeric Root Powder 

Turmeric is a bright, yellow-orange spice that is related to ginger.32 For the last 4000 years, it has been used in Chinese medicine and Ayurvedic medicine for humans. With more studies conducted over the years, many benefits have been revealed. It is not just used only for humans but for animals as well.33

Turmeric has been linked to healing and cosmetic benefits. The health benefits may come from the bioactive component, curcumin. This bioactive component has multi-dimensional benefits including potential anti-inflammatory, anti-oxidant, anti-bacterial, anti-virus, anti-fungal, healing, and anti-cancer properties.34 Thе сurсumin fоund in turmeric саn hеlр wоundѕ heals by dесrеаѕing inflammation and oxidation, resulting in the body lowering the response to cutaneous wounds. This might result in a dog’s wound healing more quickly and effectively. A 2019 study that investigated turmeric in dogs showed improvement in joints and reduced pains in dogs with advanced osteoarthritis.35 The study also found that it was well tolerated and had no adverse effects. Overall, turmeric has many multi-dimensional benefits that can aid in wound healing in dogs. 

 

Methysulfonylmethane (MSM)

Officially known as methylsulfonylmethane, MSM is an organic sulfur-containing compound that is well known for its joint health benefits.36  Sulfur is a vital element for proper biochemical functioning and it serves as a building block for amino acids, joints, cartilage, and other connective tissues. Deficiencies in biological sulfur can result in the less-than-optimal functioning of cells, tissue, and organs in the body.37 

One of the benefits of MSM is that it is a natural analgesic that inhibits the transfer of pain impulses through the nerve fibers. It has anti-inflammatory properties, by enhancing the activity of cortisol.38 This may be beneficial in wound healing by reducing pain, redness, and swelling. Several studies have shown that supplementation with MSM significantly reduces joint degeneration and inflammation. In one study, 24 people with symptomatic osteoarthritis were treated with either NSAIDs, or with 3 grams of MSM daily. After one month, both groups noted equal improvements in pain and stiffness. 

MSM may also have synergistic abilities, potentiating vitamins and nutrients such as vitamin C, B vitamins, vitamin A, vitamin D, vitamin E, amino acids, selenium, calcium,  and magnesium. All necessary for immunity and recovery from surgery. Ultimately, MSM may be a good supplement for dogs who are recovering from all types of wounds or even dogs with joint problems. 36-38

 

Vitamin C (Ascorbic Acid) 

Vitamin C is a water-soluble vitamin that is synthesized in the liver in most species, including dogs and cats. 39 Vitamin C has an important physiologic role in numerous metabolic functions including tissue growth and maintenance, protecting cells from damage due to oxidative stress, and immune regulation. Along with its effective antioxidant properties, it also possesses anti-inflammatory effects. This makes it an ideal supplement not only to boost the immune system, but to recover from any injury.  

Collagen is an insoluble protein that makes up one-third of the body’s protein. There are at least 16 types of collagen with the majority belonging to types 1, 2, and 3.40 Type 1 collagen is the most abundant and is a key structural component of several different tissues. Vitamin C plays a role in regulating the synthesis of type 1 collagen. It does this through the hydroxylation of collagen molecules which are required to maintain extracellular stability and to support the epidermis. Additionally, vitamin C stabilizes collagen mRNA, which allows an increase in collagen protein synthesis to repair damaged skin. Prolonged vitamin C deficiency in dogs causes slower wound healing.41  

Several studies have been conducted on dogs with burns. A 2009 study investigated the effect of vitamin C on alleviating peroxidative damage in the intestines of dogs during fluid resuscitation of severe burn shock. This study found a statistically significant difference from the supplementation of vitamin C, and concluded that vitamin C can reduce peroxidative damage and tissue edema. 41 Another study investigated the effects of vitamin C treatment on burn injury in the hind paws of 12 dogs. The authors concluded that administration of high-dose vitamin C reduces early postburn microvascular leakage of fluid and protein.39 These studies suggest that vitamin C supplementation has wound-healing capabilities in dogs.

 

Vitamin E (D alpha-tocopherol acetate)  

Vitamin E is a fat-soluble vitamin that is an essential component of a dog’s diet.43 It possesses powerful antioxidant properties that prevent cell damage caused by free radicals. Free radicals can cause oxidative stress which can cause severe damage to the cell membrane, proteins, DNA, and other essential parts of a dog’s organ systems.44 An antioxidant, like vitamin E, can neutralize these free radicals. It is also required for the proper function of many organs, enzymatic activities, and neurological processes. Aerobic metabolism produces reactive oxygen radicals, where an increase in vitamin E may be needed in some dogs. In one study by Scott, K et al., they investigated the effect of alpha-tocopherol supplementation on serum vitamin E concentrations in Greyhounds before and after a race.45 The findings showed that supplementation with alpha-tocopheryl acetate increased serum alpha-tocopherol concentrations after the race –  leading to a decrease in oxidation during exercise. This suggests vitamin E may improve canine performance or exercise recovery.  

Vitamin E is composed of two forms of molecules, tocopherols and tocotrienols. Tocopherols are more commonly added to pet foods and supplements as ‘mixed-tocopherols’. An important aspect of Scott, K et al. study, α-tocopheryl acetate was used for supplementation due to its stability, whereas unesterified forms of vitamin E are relatively unstable in stored foods such as kibble dog food. Alpha-tocopheryl acetate has no antioxidant activity until hydrolyzed to α-tocopherol. However, it is still a useful source of vitamin E since it is hydrolyzed within the body. The study’s results demonstrated that alpha-tocopheryl acetate appears to be absorbed and it increases circulating alpha-tocopherol concentrations.  

Commercially available pet food that meets the Association of American Feed Control Officials (AAFCO) standards will contain at least the minimum amount of vitamin E that meets a healthy dog’s needs. However, additional vitamin E could be beneficial especially when a dog experiences skin conditions. Adam Denish, VMD of Rhawhurst Animal Hospital in Elkins Park, PA reported that the decision to supplement a dog’s diet with vitamin E is that “...there is no real reason to add it to their diet. However, dogs with dry or itchy skin, or skin and ear allergies could benefit from it.” For example, in canine atopic dermatitis (CAD) low levels of plasma vitamin E concentrations were found. A study investigated the effect of an eight-week vitamin E supplementation on clinical response in dogs with atopic dermatitis.44 The authors of the study found that throughout the treatment in the vitamin E group, the severity of CAD was significantly lower than in the placebo group.  

Vitamin E is a staple of human skincare products as it is often recommended by physicians to improve the outcome of scars after skin surgery and resurfacing.43 With its ability to neutralize free radicals, it may help protect against exposure to toxins, ultraviolet rays, drugs, radiation, pollution, and smoke. This antioxidant may help prevent oxidation of cells, preventing cellular damage that can accelerate aging and disease. Vitamin E can also strengthen the capillary walls and improve moisture and elasticity, acting as a natural anti-aging nutrient within a dog’s body. Dogs use vitamin E to form collagen fibers, which are directly involved in developing hair and skin, making it good for their skin and coat.  

 

Grape Seed Extract 

Grape seed extract is a substance derived from ground-up seeds of grapes.46 It is commonly known that grapes are toxic to dogs, however, the extract of the seeds is beneficial to dogs and humans alike. A 2016 research review published by BMC Veterinary Study tested an extract of blueberries and grapes and found it did not cause renal or liver damage. 

Grape seed extract contains oligomeric proanthocyanidin complexes (OPCs), which are recognized as powerful antioxidants that help improve immune responses and nerve functionality.47 It may have anti-allergen, anti-inflammatory, and anti-mutagenic properties. OPCs have many functions including improving blood flow, and, having adequate oxygen levels is essential for proper healing. It might ease swollen joints and may help improve eye function and slow or prevent cataracts. Grape seed oil is not only full of antioxidants but it also possesses anti-anxiety and anti-stress components, which may aid in relaxation. Rest is essential during the recovery process after surgery. 

Grape seed oil also has antiseptic characteristics and may be used in conjunction with shampoo to combat fungal skin problems, infectious diseases, and parasites.48 Grape seed oil is also high in linoleic acid, a polyunsaturated omega-6 fatty acid. This essential fatty acid helps with cell membrane structure and cell function. Linoleic acid plays a crucial role in immune function and skin and coat health.46-48 

Grape seed extract with its antioxidant properties may hеlр сlеаr роtеntiаllу раthоgеniс bасtеriа frоm a wоund, increase blood flow, aid in relaxation, and help immune function, contributing to more optimal wound healing and even a shinier coat.

 

Selenium Yeast 

Selenium (Se) is an essential trace element in dogs.49  Selenium’s major function in the body is its involvement in the production of antioxidants, in particular, the antioxidant enzyme glutathione peroxidase. Free radicals result in damage to biological systems, including DNA, proteins, fats, and intracellular components – delaying the wound-healing process. 

A selenium deficiency can cause serious health problems, such as weakening joint cartilage, premature aging, heart disease, and dry flaky skin.50 Adequate levels of selenium may help prevent free radical generation, preserve tissue elasticity, slow down the aging process of tissues, and prevent dry, flaky skin. Steroids are typically prescribed after surgery, and they can deplete the natural levels of selenium in the body. This makes supplementation especially beneficial for dogs being treated with steroids. After surgery, stress on a dog can be heightened which can cause lost selenium, making less selenium available in the blood and increasing the likelihood of deficiency. 51 Post-surgery can lead to poor skin health, especially around the affected areas. As the skin heals, dogs are more likely to scratch or bite the affected area. Selenium can increase the health of the skin and potentially reduce the dryness associated with sore skin. Selenium also plays an important role in hair growth and coat quality, allowing hair to grow back healthy and strong and the coast softer and more shiny. 49-51

Selenium yeast is a natural and organic form of selenium produced by yeast. Selenium yeast closely mimics the form of selenium found in fresh food. It can be absorbed in a dog's bloodstream and is stored in their cells for use during times of stress or overexertion. Selenium yeast supports metabolism, cellular regeneration, immune response support, and healthy skin and coat, all of which are necessary during surgery recovery.   

 

Boswellia Serrata 

Boswellia, extracted from the Boswellia serrata tree in India, has long been used as a traditional herbal medicine in dogs and humans.52 It’s another powerful natural anti-inflammatory that has well-known joint support and comfort properties and has also been shown to help maintain the structural integrity of connective tissues. It has also been shown to soothe digestive issues, can help to firm loose droppings, and is thought to support the respiratory system.

The mechanism of anti-inflammatory activity of the Boswellia extract is due to the boswellic acids.53 The chemical structure of boswellic acids closely resembles that of steroids. However, their actions are different from prescription medications. Boswellic acids inhibit the enzyme 5-lipoxygenase. This enzyme contributes to chronic inflammation in diseases such as rheumatoid arthritis, osteoarthritis, cancer, and asthma. The inhibition of 5-lipoxygenase stops one of the major biochemical pathways involved in inflammation, reducing inflammation and preventing cartilage loss. The compounds in Boswellia also decrease glycosaminoglycan degradation and inhibit mediators of autoimmune disorders, slowing the progression of cartilage damage in arthritic joints. This can be exceptionally helpful in easing pain in dogs who have arthritis.54

According to research from a Swiss study, dogs with osteoarthritis and degenerative conditions given Boswellia serrata extract experienced relief from symptoms.53 The study concluded that after just two weeks of treatment, researchers found the dogs showed a 71% improvement in symptoms. Dogs showed a reduction of lameness and increased smoothness of gait after 6 weeks.

Researchers from the Regional Research Laboratory in Jammu, India found oleogum from Boswellia serrata to be effective in treating inflammation. During the study, rats with swelling in their paws experienced a 39-75% reduction of inflammation, compared to a 47% reduction from NSAIDs.52-55

The mechanism of Boswellia extract of reducing inflammation ѕuggеѕts thаt thiѕ plant extract mау aid wound healing.

 

Bromelain

Bromelain is an anti-inflammatory enzyme found in the pineapple plant.56 It digests proteins and promotes plasmin, contributing to healthy tissue. Bromelain contains, among other compounds, various closely related proteinases, exhibiting various fibrinolytic, antiedematous, antithrombotic, and anti-inflammatory activities in vitro and in vivo, thus possessing notable nutraceutical and therapeutic properties.59

Bromelain’s antiinflammatory potential is mediated through regulating several inflammatory mediators including interleukin (IL)-1β, IL-6, interferon (INF)-γ, and tumor necrosis factor (TNF)-α. 58 It modulates lymphocyte homing and migration to the sites of inflammation. Bromelain exerts potential immuno-modulatory effect through the activation of natural killer cells and enhances the production of granulocyte-macrophage-colony stimulating factor, IL-2, IL-6, and decreases the activation of T-helper cells. Bromelain mediates anti-inflammatory action by decreasing pro-inflammatory prostaglandins, reducing the level of bradykinin, and reducing plasma fibrinogen as it enhances serum fibrinolytic activity leading to less distention and permeability of capillaries. If a dog is injured or recovering from surgery, these mechanisms possessed by bromelain can help their tissues heal effectively.56

Bromelain contains escharase which is nonproteolytic, selectively acting on necrotic tissues sparing normal protein substrates or various glycosaminoglycan substrates.61 Through this, bromelain has a potential benefit in the debridement of necrotic tissue and acceleration of healing. It can accelerate the recovery of blood perfusion and partial pressure of oxygen to areas of wounded tissues. A clinical study demonstrated that bromelain orally administered to boxers completely cleared all bruises on the face and hematomas of the orbits, lips, ears, chest, and arms in four days.57 In a rat model, bromelain significantly reduced the edema in traumatically-induced hind leg edema.61 

Bromelain has notable therapeutic properties, assisting in reducing inflammation, swelling, bruising, pain, and promoting healing. This makes it a potentially beneficial supplement post-surgery for dogs and humans alike. 

 

L-arginine 

L-arginine is an essential amino acid required for dogs to support protein synthesis, growth, and biological functions.62 Specifically, the role of arginine in wound healing involves collagen synthesis. Arginine is a precursor to proline, where regulation of proline availability for collagen biosynthesis is critical to maintaining tissue integrity. Studies have shown that supplementation of arginine accelerated wound healing mаinlу bу inсrеаѕing соllаgеn dероѕitiоn in wоundѕ.63 Not оnlу iѕ соllаgеn ассumulаtiоn inсrеаѕеd bу arginine ѕuррlеmеntаtiоn, but реriрhеrаl blооd lуmрhосуtеѕ ѕhоw inсrеаѕеd mitоgеnеѕiѕ аnd activity as well. Overall, arginine is essential in the wound healing process, making supplementation potentially beneficial for collagen synthesis. 

 

Hyaluronic Acid 

Hyaluronic acid naturally occurs in the body, including the eyes and skin.64 The gel-like substance binds with water to cushion joints to mainly carry out synovial fluid functions. In dogs, osteoarthritis is very common, degrading hyaluronic acid as they age. Hyaluronic acid is commonly used as an intra-articular injection to manage osteoarthritis in veterinary medicine, in hopes of restoring joint lubrication and shock absorption while avoiding the use of long-term pain medications.66 Oral administration is less common, however, current available scientific evidence has shown some advancement. Researchers in a 2021 study found that orally administered hyaluronic acid significantly improved biomarkers of osteoarthritis in dogs.65 The study showed a significant 10-week improvement in hyaluronic acid concentration in the synovial fluid and a decrease in paraoxonase-1(considered an indicator of inflammation and oxidative damage, with its concentration decreasing as oxidative stress progresses). Overall, oral hyaluronic acid can be a potential supplement in providing optimal wound care, specifically in dogs recovering from osteoarthritis.64-66 

 

Zinc Proteinate 

Zinc is an essential trace element required for enzymatic, structural, and regulatory functions. Functions include regulation of the immune response, modulation of keratogenesis and wound healing, maintenance of normal reproductive function, and acuity of taste and smell. Zinc proteinate is an inorganic zinc, attached to organic compound proteinate, making it a chelated mineral. Because inorganic minerals are difficult to absorb by animals, chelated minerals improve the absorption, ensuring that the body gets an adequate amount of zinc.67 

There are studies conducted in other mammals showing that zinc transporters are present in skin cells of the epidermis, having an important role in health and skin homeostasis. Zinc is a cofactor of the enzyme delta-6 desaturase that catalyzes a step in the biosynthesis of linoleic acid into arachidonic acid. This is then taken up by keratinocytes and used for the formation of a functional epidermis.70 One study investigated the effects of zinc and linoleic acid on skin, hair, and coat conditions in dogs. The study found that supplementation of zinc and linoleic acid can make significant enhancements to skin and coat condition in dogs.68 Another study conducted on Siberian huskies with periocular crusts and parakeratosis showed that oral zinc ameliorated these clinical symptoms in most of the dogs in the study.69

Adequate zinc status is required for the proper function of several systems. In dogs, the role of zinc in skin health has been well documented. A dog's access to zinc depends upon oral intake, which is commonly added to pet food or even additional supplementation if needed, especially in scenarios where a dog is recovering from injury or surgery.67-70

 

Astaxanthin 

Astaxanthin is a red pigment found in fish, shrimp, and algae.75 It is classified as a ketocarotenoid, possessing many important biological properties including anti-inflammatory and antioxidant activity.71 The antioxidant activity of astaxanthin has been reported to be higher than that of α-carotene, β-carotene, lutein, and α-tocopherol. Both in vitro and in vivo studies have shown that astaxanthin can enhance humoral and cell-mediated immune responses, and suppress bacterial infection. Studies have shown that dietary astaxanthin heightened cell-mediated and humoral immune response and reduced DNA damage and inflammation in dogs.73 

Astaxanthin and vitamin E are both antioxidants that are frequently used in humans for cosmetic purposes as well as food additives, to prevent oxidative damage. A combination of astaxanthin and vitamin E would be expected to show an additive antioxidative effect. A study conducted in humans showed that the combination of astaxanthin and vitamin E induces synergistic scavenging activity, making its antioxidant activity even more effective and potent.72

Astaxanthin’s potent antioxidant properties may create an ideal supplement for aiding in wound care or injury.71-75

 

Probiotics (Lactobacillus)

Probiotics are live microorganisms necessary for maintaining homeostasis in the gut and skin. Probiotics have played a role in managing diseases and immune modification. The skin microbiota acts on keratinocytes and their cytokine release, ensuring the skin is in good condition. When a wound occurs or if a dog experiences certain inflammatory skin diseases such as atopic dermatitis, skin homeostasis is compromised. One study looked into the differences between the skin microbiomes of healthy dogs and allergic dogs. After extracting and analyzing the DNA of the dog’s skin, researchers found allergic dogs have lower species richness and diversity than healthy dogs. Supplementation of probiotics for dogs could replenish these depleted levels, helping to reduce skin allergies and aid in the wound healing process.76-80

 

Calendula Officinalis 

Medicinal plants have been traditionally used for centuries in treating wounds and skin diseases in both humans and animals.81 One of these many medicinal plants is Calendula officinalis, also known as pot marigold. Calendula officinalis belongs to the plant family Asteraceae and is native to the Mediterranean region of Europe, however, it can be found in many other parts of the world. The beneficial effects come from the broad array of compounds in the flower such as carotenoids, saponins, flavonoids, oils, and triterpene alcohols. The beneficial effects may include anti-inflammatory, antiseptic, antiviral, anti-fungal, and antibacterial healing properties.

Calendula can be used both externally and internally on dogs. Externally, this medicinal plant can keep wounds clean and help new tissue to grow, speeding up cell reproduction. It can help relieve any inflammation at the site of the wound including redness, swelling, and tenderness. This effect is due to its ability to scavenge free radicals, preventing them from causing further inflammation, and to its ability to inhibit lymphocyte proliferation. The antibacterial properties of the flower can inhibit growth at the wound site and may be used to prevent secondary infection. An additional benefit of using it topically is that it can be moisturizing, making the coat and skin shinier and smoother. It increases skin moisture content resulting in a decrease in the trans-epidermal water loss and an increased firmness of the skin. Internally, Calendula can be used to reduce inflammation, more specifically in the digestive or urinary tract. This effect can aid in stimulating the immune system since much of the immune system is connected to the digestive tract. 

Calendula is a medicinal plant with a broad array of healing properties, making it an ideal supplementation for wound care in dogs. Both externally and internally, it has been shown to reduce inflammation, making this flower a necessity in healing.81-84

 

Conclusion

Nutrition plays an important role in the wound-healing process for both humans and dogs alike. Both undergo the same wound-healing process including inflammation, debridement, repair, and maturation – each stage varying slightly depending on species. Through these intricate events, macronutrients including protein, carbohydrates, and fats, and micronutrients such as vitamins and minerals, are deeply involved. If a dog lacks certain macronutrients such as protein or certain micronutrients are diminished in their diet, it can delay the wound healing process. This may affect inflammation levels or even cause a disruption in collagen synthesis. Given the evidence, optimal nutrition and supplementation of science-based ingredients can enhance wound healing in dogs. 

Nutritional requirements, especially when the body may need more during recovery, can not always be met through diet alone. WoundVite™ for Dogs is an all-in-one effective oral supplement formula for dog wound care to help aid in tissue repair, immunity, pain, and inflammation. Each capsule is formulated with 21 different pharmaceutical-grade vitamins, minerals, and herbs, as well as five different probiotics. These evidence-based ingredients have been researched and proven safe to consume in dogs. Not only can this formulation aid in optimal wound recovery in dogs, but it may also correct nutritional deficiencies or aid in joint care. WoundVite™ for Dogs is a veterinarian-approved supplement that pet owners can give their dogs to support an easier and faster recovery after surgery or injuries. 

 

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