Understanding The Link Between Nutrition And Wound Healing

By John E. Hahn, DPM, ND

In our profession, we do not receive extensive training in medical nutrition and its link to wound healing and the prevention of infections. Most podiatric and medical school curriculums devote only a limited amount of time to nutritional instruction for their students. Granted, podiatrists are aware of the nutritional requirements for the diabetic patients. Preoperatively, we usually work alongside an internist or primary care physician to help these patients balance their insulin and glucose levels during and after the foot surgeries. However, aside from treating patients who are diabetic, morbidly obese or alcoholics, not much thought is given to a patient’s dietary habits as they relate to wound healing. The field of medical nutrition is growing significantly each year and the general public is becoming more aware of the importance of foods and food supplements in maintaining health and preventing disease. There are daily reports in both print and electronic media on health issues and the relationship to foods, beverages and supplements. Podiatrists need to take a proactive role in learning about the field of nutrition as it relates not only to wound healing but to other diseases which affect the lower extremities and feet. Diseases such as osteoporosis, arthritis, peripheral neuropathy, psoriasis and eczema all have nutritional ramifications. In fact, plantar fasciitis has recently been linked to obesity. Patients whose body mass index (BMI) is over 25 have an increased incidence of foot and heel pain.1 Augmenting the traditional podiatric therapies for plantar fasciitis and heel pain with nutritional counseling for obese patients will give a value-added service. Helping these patients reduce their weight can subsequently reduce weightbearing stress and plantar fascia pain. Choosing The Most Nutritious Diet Although there are no magic formulas for dietary recommendation to ensure wound healing in all cases, there are a few general dieting guidelines, which are supported by all major health-related organizations.2 In general, patients should consume a low-fat, high fiber diet, a nutrient dense diet that is adequate in all vitamins and minerals, on a daily basis. Avoidance of simple sugars, carbohydrates and convenience foods should be a top priority along with reducing fat intake. This diet should consist of a wide variety of fresh fruits, fresh or frozen plain vegetables and whole grain breads and cereals, beans and peas. Also on the menu are low-fat or non-fat milk products such as 1% low-fat milk and yogurt. Patients should consume small amounts of extra lean meats, chicken or fish in a ratio of 40 percent protein to 30 to 35 percent complex carbohydrates and 30 percent oils such as olive oil and sunflower oil. These oils could be added to the meal as either part of a salad dressing or a vegetable topping. In addition, daily aerobic exercise acts as an effective method of stress control. Avoidance of tobacco products and toxic elements (e.g., lead, mercury, arsenic) are important for reducing oxidation radicals within the body. Most people can tolerate alcohol in moderation and wine does have antioxidant activity. Your patients must take an active responsibility to make wise food choices or assume the risk for the unnecessary suffering that results from a lifetime of poor dietary choices. The American menu is not the only way to eat. In fact, few people in the world consume the quantity of fats, salt and sugar that Americans do on a yearly basis. It shouldn’t be a surprise that cultures of those who do eat a “Westernized” diet also have higher rates of cardiovascular disease, cancer and other degenerative diseases.3 Since most Americans do not eat a correct balance of the various foods in the aforementioned food groups, there is the possibility of lacking vital nutrients essential to wound healing. Many of these macro- and micronutrients essential for wound healing may be either greatly reduced or missing in the standard American diet. The immune system requires adequate protein, fatty acids, vitamins and minerals for normal function. There is a direct link between a healthy immune system and healthy wound healing. A “junk food” diet leads to too many calories and unhealthy fats, resulting in a form of malnutrition with too little trace minerals and vitamins that act as co-enzymes. This nutritional imbalance from a junk food diet will weaken the immune system. This reduced immune system activity may lead to delayed wound healing and wound infections. The lack of a balanced nutritional intake can be particularly problematic among elderly patients. The digestive systems of these patients do not operate in the same capacity as those of younger patients. Given the reduced digestive enzymes available, there is reduced absorption of essential nutrients for the immune system in elderly patients. How Vitamin C Facilitates Improved Healing Antioxidant nutrients such as vitamin C, vitamin E, selenium, copper, zinc and beta carotene may enhance the immune response by lowering the burden of free radicals. This protects the immune cells against the cumulative oxidation and free radical attack due to the release of powerful oxidizing agents such as super-oxide dismutase. Vitamin C is a water-soluble vitamin and easily oxidized in solution. One of vitamin C’s functions is in collagen synthesis. Hydroxyletion of proline forms prolyhydroxylase and lysylhydroxylase, which are both essential enzymes for the hydroxylysine cross-links found in collagen. Collagen is essential in proper wound healing and maintaining the integrity of the integumentary system. Ascorbic acid (vitamin C) acts as a reducing agent and keeps both of the above enzymes active. The connective tissues influenced by these two enzymes also include cartilage, dentin, skin and bones. Vitamin C is utilized by fibroblast to generate collagen components.5 In two double-blinded controlled studies, vitamin C demonstrated a statistically significant positive effect in the healing of surgical patients suffering from pressure sores.6,7 Twenty surgical patients were treated with either placebo or 1 gram of vitamin C. Forty-three percent of placebo patients had improvements compared to 84 percent of the vitamin C-treated group. The recommended daily allowance for vitamin C is 60 milligrams per day. However, to achieve therapeutic levels, daily intake should be between 1 and 6 grams per day, depending upon the individual patient’s size and weight. This increased dosage of vitamin C has been shown to enhance wound healing and stimulate the human immune system. What You Should Know About Vitamin E Vitamin E comes in several forms known as tocopherols. These are oily, yellow liquids that are water-soluble as well as heat and acid stable. There are eight known tocopherols. Of these, only four occur naturally in foods: alpha, beta, gamma and delta tocopherols. D-alpha tocopherol accounts for 80 percent of the activity of the vitamin. When you see mixed tocopherols on the label of a vitamin or mineral supplement, it indicates that 80 percent of the natural D-alpha tocopherol is present and the remaining 20 percent is a mixture of beta, gamma and delta tocopherols. The D-alpha tocopherol form of vitamin E has the most biological activity of all the forms. Vitamin E requires the presence of bile for absorption at the normal levels of intake, approximately 15 to 20 international units per day. However, only about 20 to 30 percent of vitamin E is actually absorbed to the intestinal tract. Vitamin E is an antioxidant that protects cell membranes. In particular, it protects the fatty acids against oxidative damage by inhibiting phospholipase A2 activity, which prevents release of arachidonic acid. 8 Arachidonic acid is a pro-inflammatory substance. Vitamin E also has an inhibitory effect on lipoxygenase and a stimulating effect on cyclooxygenase. This seems to be the mechanism of action for vitamin C’s antiinflammatory effects in the body. Vitamin E’s therapeutic range is 400 to 800 international units per day. The best food sources for vitamin E are wheat germ oil, sunflower seeds, almonds, pecans, soy yogurt and filberts. When you apply Vitamin E, in its liquid form, to closed wounds, its antioxidant action decreases healing time transcutaneously. How Selenium Can Make An Impact Selenium was originally believed to be a toxic element to animals and humans, due to diseases that appeared in animals who grazed on land that had high selenium levels. “Blind staggers” and “alkali disease” can occur in cattle and sheep. There are organic and inorganic forms of selenium. Selenium is involved in the synthesis of the enzyme glutathione peroxidase. This enzyme is responsible for detoxifying hydrogen peroxide (a powerful oxidizing agent) on an intracellular level. It also converts hydroperoxyeicosatetraenoic (HPETE) acid into hydroxyeicosatetraenoic (HETE) acid on an extracellular level, thereby reducing leukotriene 4 series and inflammation. It should be noted that lucotrienes are very powerful pro-inflammatory agents. The recommended daily allowance for selenium is 55 to 70 micrograms per day. The optimal daily intake should be in the range of 200 to 300 micrograms a day, depending upon toxin exposure. Keep in mind that 900 to 1,000 micrograms a day is the highest level of selenium that can be taken without the development of toxicity in most people.9 What Role Does Copper Play In Wound Healing? Copper is found in its highest concentrations in the brain, liver, heart, bones, teeth and kidneys. Approximately 90 percent of copper in the blood is bound as ceruloplasmin and the rest is bound to albumin and amino acids. Copper is a divalent cation fructose and sucrose can inhibit its absorption from the diet. Some copper can be absorbed from the stomach but the majority is absorbed from the small intestines. Copper functions as a co-factor for several enzyme systems, including cytochrome oxidase, dopamine hydroxylase, tyrosinase and ceruloplasmin. Ceruloplasmin is a broad spectrum oxidase and its main function is as an extracellular scavenger of super-oxide and other oxygen radicals in copper transport and in antioxidant defense. Ceruloplasmin is intimately involved in detoxification. It also acts as a co-factor by reducing iron into the ferrous form, making it much more absorbable through the GI tract. It also facilitates availability from the liver. Lysyl oxidase is a copper-containing enzyme secreted by connective tissue cells that aid in the cross-linking of elastin and collagen. This role that copper plays with lysyl oxidase makes copper indispensable for connective tissue repair. Copper, in its astitute form, has been used by various drug manufacturers in topical preparations for wound healing. Applying this copper solution topically has demonstrated effectiveness in increasing the activity of wound healing.10 There is an increase in serum copper by 20 to 30 percent during inflammatory conditions. Through the action of ceruloplasmin, which acts as a free radical scavenger, and superoxide dismutase (SOD), copper plays a pivotal role in decreasing inflammation. There is no RDA (recommended daily allowance) for copper intake but the estimated safe and adequate daily dietary intake for copper is between 1 and 3 milligrams per day. The best food sources for copper are beef liver, rye, dried beans, brazil nuts, cashews, dried and cooked peas and black strap molasses. A deficiency of copper can cause hemolysis with liver and brain damage and anemia. Copper is essential for the immobilization of iron from the liver. A deficiency of copper may result in micocytic anemia. Large doses of copper may cause nausea and vomiting. Long-term supplementation of large doses of copper may cause cirrhosis of the liver. Be aware that non-steroidal anti-inflammatory drugs (NSAIDs) and penicillamine may cause copper deficiency. Chronic copper steroid intake, which weakens connective tissue, may also cause a copper deficiency. Also keep in mind that there is a strong relationship between zinc and copper. Iron can interfere with copper absorption.11 What About Zinc? Zinc supplements come in many forms: zinc picolinate, citrate, aspartate, gluconate and oxide. Zinc is stored in the muscles, spleen, bone marrow and liver. There are high concentrations of zinc in skin, the prostate and the retina, especially the macular of the retina. Zinc is involved in the synthesis of cholesterol, protein and fats. It helps regulate the release of vitamin A from the liver. Zinc affects cell growth of epithelial tissue. Zinc is an antioxidant co-factor for super oxide dismutase. Zinc is required for proper insulin function and immune system function. The best food sources of zinc are Swiss chard, Swiss cheese, cheddar cheese, dark turkey meat, wheat germ, roast beef, Pacific oysters and Eastern oysters. The recommended daily allowance of zinc is 15 milligrams per day. The optimal dose for therapeutic levels is 30 to 50 milligrams per day. Zinc has been shown to be helpful in treating rheumatoid arthritis due to its involvement as an antioxidant to the enzyme super oxide dismutase. Zinc levels were found to be low in patients suffering with RA.12 Zinc applied topically or orally has been shown to enhance wound healing. Zinc is involved as a co-factor with Delta 6 desaturase in the production of PGE1. PGE1 acts as an antiinflammatory agent both internally and externally. Zinc oxide ointment, especially for infants, has been shown to reduce inflammation of the skin and aid in wound healing. A Few Thoughts About Vitamin A The term vitamin A is used to refer to the alcohol, aldehyde and acid forms of vitamin A, all of which are biologically active. The carotenoids (alpha, gamma and beta) are converted to vitamin A primarily in the intestinal mucosa. Beta-carotene is considered to be significantly less biologically active than pure rentinol. Rentinol, or vitamin A, occurs in three forms: alcohol, aldehyde and acid. Beta-carotene is stored in fat deposits and the adrenals rather in the liver. Serum levels of beta carotene directly reflect daily consumption, not storage. Both thyroxin and vitamin E enhance the conversion of carotene to rentinol. Most ingested rentinol is stored in the liver and rentinol storage has a half-life of 50 to 100 days. The function of rentinoic acid involves vision, growth and bone development, epithelial tissue development and maintenance, immunity, reproduction and anti-cancer functions. The best food sources for beta-carotene or rentinol are beef liver, chicken liver, cooked dandelion leaf, cod liver oil, steamed burdock and pork liver. Vitamin A or rentinoic acid is needed for the differentiation of basal cells into mucus epithelial cells. Vitamin A or rentinoic acid is essential in the formation and regeneration of epithelial cells. The recommended daily allowance of vitamin A is 5,000 international units. This allowance assumes a mixed diet of two-thirds vegetables and one-third animal sources of vitamin A. The recommended daily allowance for women is 4,000 international units. When it comes to rentinol, the optimal daily intake is 15,000 international units although you should inform your patients that they need to exercise caution during early pregnancy. The optimum daily dose of beta-carotene is 25,000 international units per day.13 In Conclusion We can see from the preceding discussion that there are various macronutrients that we derive from our food sources and micronutrients that we can obtain from food sources and supplements that are essential in proper wound healing. As podiatric physicians, we need to extend the scope of our services to our patients by augmenting our armamentarium with appropriate nutritional counseling and advice. Indeed, we need to become proactive in acquiring knowledge of nutriceuticals and dietary programs for our patients. This will aid our patients not only in wound healing but in their general overall health status. Dr. Hahn practices at Trinity Clinic, Inc. in Bend, Ore. He is board-certified by the American Board of Podiatric Surgery and is a member of the American Association of Naturopathic Physicians. Editor’s Note: For a related article, see “Can Nutritional And Metabolic Influences Improve Wound Healing?” in the December 2000 issue at www.podiatrytoday.com. CE Exam #105 Choose the single best response to each question listed below: 1. A BMI of 25 or over can contribute to the following conditions: a) Bunions b) Plantar warts c) Plantar fasciitis d) Hammertoes 2. A “Westernized” diet has the following characteristics: a) consumption of adequate amounts of fresh fruits and fresh or frozen plain vegetables, whole grain breads and cereals, low-fat or non-fat milk b) diet dominated by saturated fats, refined sugars, moderate alcohol intake, increased salt and refined foods c) a vegetarian diet d) a predominantly animal protein diet 3. All of the following are antioxidant nutrients except: a) D-Alpha tocopherol b) Zinc c) Iron d) Ceruloplasmin 4. Vitamin C functions in collagen synthesis by: a) hydroxyletion of proline b) inactivation of lysyl hydroxylase c) acting as an oxidizing agent for prolyl hydroxylase d) reducing iron 5. The RDA for vitamin C is: a) 1,000 milligrams twice a day b) 60 milligrams per day c) 2 grams three times a day d) 100 milligrams three times a day 6. Vitamin E acts as a protective antioxidant by the following mechanism: a) protects arachidonic acid from oxidation b) accelerates the activity of lipo oxygenase c) participates in the oxidation of fatty acids d) functions as an antioxidant protecting cell membranes 7. Selenium was originally thought to be: a) a toxic element to animals and humans b) a cure for blind staggers c) only occurring in an inorganic form d) responsible for macular degeneration 8. Glutathione peroxidase is responsible for: a) oxidizing vitamin C b) acting as an enzyme for creating intra-cellular hydrogen peroxide c) converting each HETE to HPETE d) reducing leukotriene 4 series and inflammation 9. Superoxide dismutase (SOD) is an enzyme that needs the involvement of the following micronutrient to function: a) Iron b) Copper c) Manganese d) Zinc 10. Beta-carotene blood levels reflect dietary carotene and functions in all of the following except: a) growth and bone development b) epithelial tissue development and maintenance c) wound healing d) benign prostatic hypertrophy



References 1. The Journal of Foot and Ankle Surgery, Vol. 4, No. 6, November-December 2001. “Correlation of Heel Pain with Body Mass Index and other Characteristics of Heel Pain,” James A. Rano, DPM, and Loris M. Fallat, DPM. 2. The Nutrition Desk Reference, 1995. Garrison R Jr., Sommer E. Pps. 417-418. 3. The Nutrition Desk Reference, 1995. Garrison R Jr., Sommer E. Pps. 545-546. 4. The Encyclopedia of Nutrition and Good Health. Ronzio RA, 1997. Pps. 244-245. 5. Pot GN. Gerlack, Enzyme, 25: 395, 1980. 6. British Journal of Nutrition, 1970. 7. British Journal of Dermatology, 1975. 8. Packer L, “Interaction Among Antioxidants in Health and Disease - Vitamin E and Its Redox Cycle.” 200: 271-276, 1992. 9. Selenium, Hou J, et. al.; “Inhibitory Effect of Selenium on Complement Activation and Its Clinical Significance.” Chung-Hua-I-Hsueh-Tsa-Chin, 73, (11)a. 645-656 and 699, 1999. 10. Product, “IAMIN with Copper Peptide,” Distributed by Persite Corporation, Redmond, WA. 11. Marz RB: Medical Nutrition, Sec. Ed., Omni Press, August 7, 1997, Pps. 125-128. 12. Simkin PA, “Oral Zinc Sulphate in Rheumatoid Arthritis. Lancet, 2: 539-542, 1976. 13. Marz RB: Medical Nutrition, Sec. Ed., Omni Press, August 7, 1997, Pps. 167-194.


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