For patients with wounds, vitamin D can be valuable, as it can promote angiogenesis, can reduce inflammation, and can improve insulin resistance. This author reviews the factors that can put patients at risk for vitamin D deficiency and how supplementation can lead to better wound healing.
The entire world is waiting for a therapeutic agent or vaccine to treat COVID-19, the disease caused by the novel coronavirus officially identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The global pandemic has shown no signs of ending but there have been rumors that researchers are getting closer to a solution. Several different drugs and a variety of treatments have been splashed across the headlines as possibilities. The rumored cures have included everything from drugs to plasma treatments to light therapy, and have ranged from plausible to laughable to even dangerous.
Among the proposed theories is one that seems so simple, it might get overlooked. A number of recent studies have implied that vitamin D could play a role in COVID-19—from preventing infection to making the disease less severe.1 This theory has a long way to go before becoming a mainstream treatment for COVID-19, but it is still worth focusing on vitamin D for a variety of reasons. In the 1980s, sun exposure was demonized and we became an indoor society. Because sun exposure is one of the best ways to obtain vitamin D, the lack of sunshine plus zealous use of sunscreen has contributed to a vitamin D-deficient society. Vitamin D deficiency is a global health problem but many physicians do not adequately address it.
For wound healing, we know vitamin D is important for promoting angiogenesis and mitigating inflammatory responses. It also has been shown to decrease the risk of type 2 diabetes by 13% compared when comparing vitamin D intake >500 international units (IU)/day to vitamin D intake <200 IU/day.2 In addition, vitamin D has the potential to improve insulin resistance, which could be beneficial to the treatment of diabetic foot ulcers. Clinicians may want to begin taking a closer look at vitamin D status especially in patients with chronic and non-healing wounds.
Forms of Vitamin D
Vitamin D actually refers to a pair of inactive precursors to a critical hormone. Cholecalciferol, more commonly known as D3, is produced in the skin after exposure to ultraviolet B light (UVB) or from foods we consume. Ergocalciferol, also known as D2, is produced in plants and enters the body through diet. Once D2 and D3 are present in circulation, they are bound to vitamin D-binding proteins (VDBP) and hydroxylated in the liver to form 25-hydroxyvitamin D (25[OH]D) or calcidiol. A further conversion in the kidney changes the calcidiol to 1,25-dihydroxyvitamin D (1,25[OH]2D) or calcitriol.
Calcidiol is the main circulating and storage form of vitamin D in the blood, with a half-life of approximately 3 weeks. This is the preferred form to evaluate vitamin D status in patients. Because the production of calcitriol is tightly regulated with a half-life of only 4 to 6 hours, its measurement is usually only of interest in renal disease or primary hyperparathyroidism.3
Vitamin D Deficiency
Numerous risk factors may predispose an individual to vitamin D deficiency:4
• Limited sun exposure, including constant use of sunscreens when outdoors. Sunscreens with a sun protection factor (SPF) of 15 block 99% of the UVB rays that make vitamin D in our skin.
• Cultural dress, such as hijabs or burkas worn by Muslim women.5
• Limited intake of foods that provide vitamin D, such as fortified milk, fortified cereal, and fatty fish.
• Living 40º north of the equator. The farther a person lives from the equator, the less his/her exposure to UVB rays and the less vitamin D produced by the body;
• Limited use of vitamin D supplements. Typical multivitamins do not provide an adequate amount of vitamin D for optimum health if other sources are not present.
• Dark complexions. People with darker complexions (e.g., individuals from Africa, East India, and the Caribbean) may require up to six times the amount of sun exposure to form the same amount of vitamin D from the sun as light-skinned people.
• Aged skin. In general, people >60 years of age have a 25% reduction in cutaneous formation of vitamin D. Senior citizens who are homebound or in long-term care facilities are at very high risk for vitamin D deficiency.
• Obesity. Because vitamin D is fat-soluble, it appears to be sequestered in adipose stores and not released easily into the blood for use by the body.
• Malabsorption disorders, including Crohn’s disease, celiac disease, and cystic fibrosis. Patients who have undergone gastric bypass surgery for weight loss also are at risk.
• Kidney disease. Supplementation of the calcidiol form of vitamin D often is started too late in many patients with renal disease. A 20% increase in mortality is seen in patients not given vitamin D.6
• Infants breastfed exclusively who are not receiving a vitamin D supplement, unless the mother is on a high dose of supplements herself.
• Certain medications that can impair absorption (e.g., phenytoin and cholestyramine). Other medications necessitate limited sun exposure because of photosensitivity—for example, amiodarone, tetracyclines, and sulfonamides.
Evaluating these risk factors is important for every patient, because the list of diseases and health problems caused or worsened by vitamin D deficiency is extensive. This includes rickets, osteoporosis, osteomalacia, frequent bone fractures, frequent falls, muscle pain and weakness, heart disease, congestive heart failure, hypertension, diabetes, some types of cancer, fibromyalgia, preeclampsia in pregnancy, autoimmune disorders such as rheumatoid arthritis and multiple sclerosis, depression, brain development, migraines, flu, pneumonia, tuberculosis, and periodontal disease.4
Adequate Intake Guidelines
For most adults, the recommended dietary allowance (RDA) is 600 international units (IU). For those >70 years of age, the current recommendation is 800 IU. The tolerable upper limit for adults is 4,000 IU.7 Vitamin D toxicity is rare but can occur.
Vitamin D Intake and Supplementation
Very few foods in nature contain vitamin D. Fatty fish and cod liver oil are among the best sources. In the American diet, most of the vitamin D comes from fortified foods. For example, milk, breakfast cereals, and some brands of orange juice are fortified. Reading the nutrition facts label is the best way to confirm the amount of vitamin D in a particular food.
Americans spend billions of dollars on various supplements each year. Some people feel this is money well spent while others question its value. There is no consensus on the optimal level of 25(OH)D but it is generally accepted that serum levels <20 nanograms (ng)/milliliter (mL) represents a deficiency state.
Treatment is usually with much higher amounts of vitamin D than can be obtained in nonprescription supplements. Vitamin D is commercially available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol). They differ chemically only in their side-chain structure. Vitamin D2 is manufactured by the UV irradiation of ergosterol in yeast, and vitamin D3 is manufactured by the irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol. Many experts prefer D3 because they believe there’s more evidence pointing to its benefits, but some studies have found D2 works just as well.4
In order to replete a deficiency quickly, prescription supplements containing 50,000 IU of vitamin D per week for at least 8 weeks are suggested.4 After 8 weeks, blood levels are retested to determine if this level of supplementation needs to be continued. If the result is <30 ng/mL, continuation of prescription level supplementation is recommended. Once 30 ng/mL is reached, daily supplements of a lower dose are continued along with periodic monitoring of serum levels. Currently, over-the-counter products range from 400 to 2,000 IU; thus, it is important to read the product label carefully.
It is important to note that researchers have not identified a universal vitamin D dosage that will consistently suit the needs of all patients. Individual medical history, lifestyle, geographic location, body composition, and other factors all play a role in determining the proper dose. Furthermore, some diseases limit the use of vitamin D supplementation, such as sarcoidosis, primary hyperparathyroidism, oat cell lung cancer, and non-Hodgkin’s lymphoma. These considerations reinforce the need for a knowledgeable physician and registered dietitian (RD) to ensure proper treatment and monitoring.4
Vitamin D and Wound Healing
Research has found that injury causes skin cells to require additional vitamin D. The genes controlled by vitamin D promote creation of an antimicrobial peptide called cathelicidin, which the immune system uses to fight infections. Skin wounds require vitamin D3 to protect against infection and begin the normal repair process. A vitamin D deficiency may compromise the body’s innate immune system, which works to resist infection, making a patient more vulnerable to microbes. These responses are a previously unrecognized part of the human injury response.8 This innate immunity process also links adequate vitamin D levels to the possible reduction in influenza and tuberculosis risk.
Rigorous studies on how the correction of a vitamin D deficiency may hasten wound healing still are needed. At this juncture, the substantial portion of the evidence is anecdotal. An often told story describes how a pain management physician approached care of a 75-year-old woman who weighed 250 pounds. The physician prescribed 50,000 IU of vitamin D per week for underlying osteoporosis. When he saw the patient for a follow-up exam, he discovered she had taken the vitamin D supplement daily instead of weekly. The physician then noticed that the patient had remarkable healing of venous stasis ulcers in her bilateral lower extremities. These ulcers previously had remained stagnant for more than 5 years, despite the best efforts of the local wound care clinic.
Caroline Fife, MD, has also published observations that vitamin D deficiency is rampant in wound patients.9 She tells the story of a 70-year-old man who underwent podiatric surgery for a ganglion cyst. His wound had difficulty healing after the sutures were removed; the wound bed that was pale and without any granulation tissue. His vitamin D level was low so Dr. Fife ordered 50,000 IU supplementation and witnessed tremendous improvement after only three weeks. Hopefully in the near future, we will see more formal studies on this topic. Vitamin D just might take a place next to the other nutrients that are essential for wound healing.
• The correct test for evaluating vitamin D (also known as calcidiol) status is 25(OH)D.
• It is only necessary to test (1,25[OH]2D), or calcitriol, if the patient has advanced kidney disease, a high calcium level, or certain diseases that induce a vitamin D hypersensitivity.
• Research now shows that activated vitamin D (calcitriol) is made in most tissues and cells, not only in the kidneys, as was previously believed.
• Vitamin D fortification is required only in liquid milk. Other dairy products do not provide vitamin D unless specified on the label.
• Sensible exposure for the face, arms, and legs to the sun should include approximately 15 to 20 minutes before applying sunscreen at least three times/week. It is estimated that a light skinned person could make 10,000 IU of vitamin D during that time.
• Always make sure to request and review the actual test results because different labs use different amounts to define normal limits.
• In this day of advanced medicine, don’t forget to check for basic nutrient deficiencies that may help preserve the quality of life and may even improve wound healing.
Dr. Nancy Collins is a wound care-certified dietitian specializing in the relationship between nutrition and wound healing. She is also a medico-legal expert dedicated to improving provider-patient communication and bettering the patient experience. To contact her, visit her website, www.drnancycollins.com.
1. Macmillan C. Vitamin D deficiency and COVID-19: Is there a connection. Yale Medicine. June 11, 2020. Available at https://www.yalemedicine.org/stories/vitamin-d-covid-19/. Accessed July 3, 2020.
2. Mitri J, Muraru M, Pittas A. Vitamin D and type 2 diabetes: a systematic review. Eur J Clin Nutr. 2011; 65:1005–1015. https://doi.org/10.1038/ejcn.2011.118.
3. Wootton AM. Improving the measurement of 25-hydroxyvitamin D. Clin Biochem Rev. 2005;26(1):33-36.
4. Holick M. Vitamin D. deficiency. N Engl J Med 2007; 357:266-281 DOI: 10.1056/NEJMra070553.
5. Ajmani SN, Paul M, Chauhan P, Ajmani AK, Yadav N. Prevalence of vitamin D deficiency in burka-clad pregnant women in a 450-bedded maternity hospital of Delhi. J Obstet Gynaecol India. 2016;66(Suppl 1):67-71. doi:10.1007/s13224-015-0764-z.
6. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):1730–1737. doi:10.1001/archinte.167.16.1730
7. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
8. Schauber J, Gallo RL. The vitamin D pathway: a new target for control of the skin's immune response? Exp Dermatol. 2008;17(8):633-639. doi:10.1111/j.1600-0625.2008.00768.x
9. Fife C. Don’t miss this! The vitamin D deficiency epidemic. Available at https://carolinefifemd.com/2018/01/23/dont-miss-this-the-vitamin-d-deficiency-epidemic-and-yes-that-is-a-pulsating-dorsalis-pedis-artery/. Accessed July 3, 2020.