Should We Be Supplementing Vitamin C and Zinc?

Question: I have been a wound care nurse in long-term care for more than 20 years. We used to automatically order vitamin C and zinc supplements for every patient with a pressure injury or chronic wound, but that is no longer the facility policy. Are vitamin C and zinc still important for wound healing? If so, shouldn’t I order supplements?

Answer: Nutritional science is constantly evolving, and recommendations change over time. We must adjust our practices as new evidence comes to light. Vitamin C and zinc play important roles in wound healing; that has never been in question. What has changed is how we look at each patient as an individual and determine if supplementation is needed based on the totality of food intake, other vitamin and mineral supplements prescribed, oral nutritional supplements, comorbidities, and care goals. Routinely giving vitamin C and zinc supplements to every patient with a wound is not consistent with truly individualized care. It is important to understand why you are prescribing these supplements, the daily requirements, and what foods can meet those requirements.

Functions of vitamin C. Vitamin C has many physiologic functions in the human body. It often is aligned with wound healing because of its role in collagen formation. Vitamin C is a cofactor in proline and lysine hydroxylation, a necessary step in collagen formation. Hydroxyproline and hydroxylysine are essential for stabilizing the triple helix structure of collagen with strong hydrogen bonds and crosslinks. Without this stabilization, the structure disintegrates rapidly.¹ Vitamin C also provides tensile strength to newly built collagen; otherwise, new tissue could not stretch without tearing. Tensile strength is important in pressure injury (PI) healing because healed PIs are susceptible to future skin breakdown. Vitamin C also is required for proper immune system function, a consideration in patients with open wounds.

Other chief functions of vitamin C include that it is an antioxidant to inhibit damage to body cells; is an anti-inflammatory; is necessary for the synthesis of carnitine, a molecule essential for the transport of fat to mitochondria; plays a role in the synthesis of the neurotransmitter norepinephrine; protects iron in the intestines from oxidation and promotes absorption; and protects vitamin E in the blood from oxidation and may recycle it to its active form.²

Functions of zinc. Zinc is an essential mineral and is a component of almost every living cell in the body. Zinc stimulates the activity of approximately 100 enzymes, including about 2 dozen known zinc metalloenzymes. Zinc plays a role in all stages of wound healing with functions ranging from membrane repair, reduction of oxidative stress, coagulation, inflammation and immune defense, tissue reepithelialization, angiogenesis, and fibrosis/scar formation.³ All proliferating cells, including inflammatory cells, epithelial cells, and fibroblasts, require zinc. In addition, zinc plays a central role in the immune system and is necessary for antibody production and proper activity of lymphocytes. Zinc also functions as an antioxidant and a membrane stabilizer and has many roles in basic cellular functions, such as DNA replication, RNA transcription, and cell division. Zinc also plays a role in taste acuity and sense of smell, interacts with platelets, and participates in the synthesis, storage, and release of insulin.

Daily requirements. Before we can answer the question regarding the appropriateness of supplementation, we must first understand the baseline requirements. Nutritional requirements are determined by the National Academy of Sciences Food and Nutrition Board of the Institute of Medicine. Each dietary reference intake includes a recommended dietary allowance (RDA) and an upper limit (UL). The RDA may be used as a goal for individual intake. RDAs are set to meet the needs of almost all individuals (97% to 98%) in a group.⁴ The UL represents the maximum daily intake likely to pose no risk of adverse effects. RDAs are based on healthy people. For vitamin C, the RDAs for women and men are 75 mg/day and 90 mg/day, respectively. The UL is 2000 mg/day; taking more than this amount may promote gastrointestinal distress and diarrhea. For zinc, the RDA is 8 mg/day for women and 11 mg/day for men. The UL is 40 mg/day. Patients with nonhealing and chronic wounds often have many other medical problems and would not generally be thought of as healthy. The RDAs are a good starting point but are not the entire answer because they leave us with the question of how to adjust these recommendations for medically challenged patients.

Food first. In an ideal world, an adequate supply of micronutrients would come from various foods consumed during meals and snacks. Today many people turn to highly processed and convenience foods and may not be meeting all their nutritional requirements from the foods they eat. Patients with acute or chronic illnesses may have additional metabolic needs, poor appetites, depression, medication interactions, financial challenges, and frailty that may limit food shopping and preparation. For these reasons and more, supplementation has come into vogue, with the nutritional supplement industry valued at $151.9 billion in 2021 and expectations to expand at a compound annual growth rate of 8.9% from 2022 to 2030.⁵

Foods high in vitamin C.⁶Most people recognize citrus fruits, such as oranges and grapefruits, as good sources of vitamin C. Many other sources provide more than 20% of the RDA in a typical serving, including kiwifruit, green peppers, strawberries, broccoli, vegetable juice cocktail, Brussels sprouts, cantaloupe, pineapple, cauliflower, tomato juice, and cabbage. Vitamin C is a water-soluble vitamin. These vitamins are not stored in the body and must be replenished daily. Vitamin C is the most unstable of all water-soluble vitamins; cooking, handling, and processing affect its content in food. The vitamin is destroyed easily by oxygen, alkalis, and high temperature; it also reacts with the metallic ions of iron and copper. Patients should be encouraged to consume at least one daily serving of a vitamin C-rich food.

Foods high in zinc.⁷Oysters are the richest source of zinc. Other foods high in zinc include red meat, shellfish such as Alaskan king crab and lobster, fortified breakfast cereals, pork chops, dark meat chicken, yogurt, baked beans, pumpkin seeds, and cashews.

Considerations for supplementation. For patients with wounds, routinely ordering vitamin C and zinc supplements is no longer the trend. Instead, a nutrition-focused physical examination, coupled with a close look at food intake, weight history, wound severity including drainage, and realistic care goals, should be done to determine the patient’s needs. Although there is scant literature on exact optimal supplementation levels in wound healing, there is consensus that any nutritional deficiencies should be corrected with supplements.

Before deciding whether additional vitamin C is needed, consider some other factors. First, the human body excretes increased vitamin C when stressed. Therefore, a deficiency may exist in many patients. Second, vitamin C is safe and relatively inexpensive. Third, adverse effects are unlikely at typical supplementation levels of 500 mg twice daily (well below the tolerable upper limit of 2000 mg/day set out in the dietary reference intake). If any adverse effects occur, they could be reversed simply by stopping the supplement. Fourth, vitamin C is water-soluble with any excess excreted in the urine. Fifth, although the clear evidence for supplementation beyond the RDA in patients with PIs may be lacking, vitamin C provides many other benefits, particularly in immune function. On the flip side, caution should be exercised when prescribing vitamin C for patients who are prone to kidney stones, those with renal disease, and those who have iron overload.

Zinc is not water-soluble and is stored in the body, so it is a little more complicated than vitamin C. If you suspect a deficiency, steps should be taken to correct it. The difficulty is that the widely used biomarkers of zinc status, such as plasma, whole blood, and urine zinc, are not reliable enough to assess zinc status, especially in mild to moderate deficiency.⁸ Fortunately, researchers are working on new methods to assess zinc status. Meanwhile, looking for the signs and symptoms of deficiency is advised. These signs include loss of appetite and impaired immune function. In more severe cases, zinc deficiency causes hair loss, diarrhea, delayed sexual maturation, impotence, hypogonadism in males, eye and skin lesions, weight loss, delayed wound healing, taste abnormalities, and mental lethargy.⁷ Clearly, many of these symptoms are nonspecific and often associated with other conditions. Because zinc deficiency is difficult to assess, many health care facilities supplement zinc for stagnant wound healing but only for a limited period. For example, a policy may call for zinc supplement for 2 to 4 weeks and include a stop order to allow for reevaluation. The assumption is that if the wound begins to make progress, perhaps there was a deficiency. If not, maybe it is not needed.

Before supplementing, it is important to look carefully at all the sources of zinc the patient may be receiving. These include ready-to-drink supplements, powdered wound supplements, liquid protein modular supplements, daily multivitamins with minerals, and the meals consumed. The totality of zinc from all sources may be surprising and approach the UL of 40 mg/day. Higher doses of zinc may cause vomiting, diarrhea, headaches, exhaustion, a metallic taste, and other symptoms.

PRACTICE POINTS

Nutrition care of patients with wounds is constantly evolving. Each patient presents with a unique history, nutritional status, and prognosis. Rather than a one-size-fits-all approach, assess patients on an individual basis using a nutrition-focused physical examination coupled with detailed dietary and wound information to determine what, if any, supplementation is needed. Vitamin C and zinc have clearly identified roles in wound healing and must be onboard in the required amounts to build new collagen. Their importance is not debated, but no vitamin or mineral can substitute for basic good nutrition. Any underlying nutritional problems, including unintended weight loss, must be simultaneously corrected to achieve the best possible outcome.

REFERENCES

1. DePhillipo NN, Aman ZS, Kennedy MI, Begley JP, Moatshe G, LaPrade RF. Efficacy of vitamin C supplementation on collagen synthesis and oxidative stress after musculoskeletal injuries: a systematic review. Orthop J Sports Med. 2018;6(10):2325967118804544. doi:10.1177/2325967118804544

2. Litwack G. Vitamins and nutrition. In: Litwack G, ed. Human Biochemistry. Elsevier; 2018: Chapter 20.

3. Lin P-H, Sermersheim M, Li H, Lee PHU, Steinberg SM, Ma J. Zinc in wound healing modulation. Nutrients. 2018; 10(1):16. doi:10.3390/nu10010016

4. US Department of Health and Human Services. National Institutes of Health. Office of Dietary Supplements. Nutrient recommendations: dietary reference intakes (DRI). Accessed May 23, 2022. https://ods.od.nih.gov/HealthInformation/Dietary_Reference_Intakes.aspx

5. Grandview Research. Dietary supplements market size, share & trends analysis report by ingredient (vitamins, minerals), by form, by application, by end user, by distribution channel, by region, and segment forecasts, 2022–2030. Report ID: 978-1-68038-919-7. Accessed May 23, 2022. https://www.grandviewresearch.com/industry-analysis/dietary-supplements-market#:~:text=Report%20Overview,8.9%25%20from%202022%20to%202030.

6. National Institutes of Health. Fact sheet for health professionals. vitamin C. Accessed May 23, 2022. https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/#en8

7. National Institutes of Health. fact sheet for health professionals. Zinc. Accessed May 23, 2022. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/.

8. Cheng J, Bar H, Tako E. Zinc status index (ZSI) for quantification of zinc physiological status. Nutrients. 2021;13(10):3399. doi:10.3390/nu13103399

Dr. Collins is a wound care-certified registered dietitian based in Las Vegas, NV. She is well known for her expertise in the complex relationships among malnutrition, body composition, and tissue regeneration. She can be reached through her website, www.drnancycollins.com.

The opinions and statements expressed herein are specific to the respective authors and not necessarily those of Wound Management & Prevention or HMP Global. This article was not subject to the Wound Management & Prevention peer-review process.