Continuing Education Activity
Vitamin C is a water-soluble vitamin, antioxidant, and essential co-factor for collagen biosynthesis, carnitine and catecholamine metabolism, and dietary iron absorption. Humans are unable to synthesize vitamin C, so it is strictly obtained through the dietary intake of fruits and vegetables. Citrus fruits, berries, tomatoes, potatoes, and green leafy vegetables are excellent sources of vitamin C. Although most vitamin C is completely absorbed in the small intestine, the percentage of absorbed vitamin C decreases as intraluminal concentrations increase. Proline residues on procollagen require vitamin C for hydroxylation, making it necessary for the triple-helix formation of mature collagen. The lack of a stable triple-helical structure compromises the integrity of the skin, mucous membranes, blood vessels, and bone. Consequently, a deficiency in vitamin C results in scurvy, which presents with hemorrhage, hyperkeratosis, and hematological abnormalities. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, and monitoring, of vitamin C so providers can direct patient therapy in treatment or supplementation where it is indicated as part of the interprofessional team.
Objectives:
Explain the role and pharmacology of vitamin C in human physiology.
Summarize the dietary sources for vitamin C.
Identify vitamin C deficiency by name and give the prominent signs and symptoms of such deficiency.
Review the importance of collaboration and coordination among the interprofessional team and how it can enhance patient care with vitamin A to improve patient outcomes where vitamin C supplementation is indicated.
Indications
Vitamin C is a water-soluble vitamin, antioxidant, and essential co-factor for collagen biosynthesis, carnitine and catecholamine metabolism, and dietary iron absorption. Humans are unable to synthesize vitamin C,so they can only obtain it through dietary intake of fruits and vegetables. Citrus fruits, berries, tomatoes, potatoes, and green leafy vegetables are excellent sources of vitamin C. Although most vitamin C is completely absorbed in the small intestine, the percentage of absorbed vitamin C decreases as intraluminal concentrations increase. Proline residues on procollagen require vitamin C for hydroxylation, making it necessary for the triple-helix formation of mature collagen. The lack of a stable triple-helical structure compromises the integrity of the skin, mucous membranes, blood vessels, and bone. Consequently, a deficiency in vitamin C results in scurvy, which presents with hemorrhage, hyperkeratosis, and hematological abnormalities.[1][2][3][4][5]
Vitamin C deficiency usually arises in the setting of decreased intake or increased requirements or losses. Personsat risk for inadequate intake of the vitamin include patients in the following groups:
The elderly
Those with alcohol use disorder, anorexia, or cancer
Practicing food fads
Those with presumed food allergies
Receiving unsupplemented parenteral nutrition
Those on restricted diets secondary to inflammatory bowel disease, gastrointestinal reflux, or Whipple disease
Those who smoke tobacco products
Taking medications such as aspirin, indomethacin, oral contraceptives, tetracyclines, and corticosteroids.
Those who have renal failure due to filtration of water-soluble vitamin C during dialysis
Those with a complication of interleukin-2 treatment of metastatic renal cell carcinoma
Receiving liver transplants
Indications
Scurvy
Vitamin C is indicated to prevent and treat scurvy. Scurvy develops 1 to 3 months after initiating a vitamin C deficient diet. Individuals may complain of lethargy, fatigue, malaise, emotional lability, arthralgias, weight loss, anorexia, and diarrhea. They also may experience easy bleeding, bruising, and poor wound healing. The cutaneous manifestations of scurvy include phrynoderma, corkscrew hairs, perifollicular hemorrhage and purpura, edema of the lower extremities, and splinter hemorrhages. Phrynoderma, or enlarged hyperkeratotic hair follicles, initially present on the posterolateral arms. This presentation subsequently generalizes to involve the buttocks, posterior thighs, calves, shins, and back. Corkscrew hairs represent fractured and coiled hairs due to impaired keratin cross-links by disulfide bonds. With time, significant vascular congestion occurs, particularly in the lower extremities, leading to perifollicular hemorrhage and edema. This purpura is occasionally palpable, mimicking a cutaneous vasculitis. Blood vessel wall fragility also results in splinter hemorrhages of the nail bed. Oral disease is prominent among those with pre-existing poor dentition. Individuals may develop hemorrhagic gingivitis, where the gingiva is initially red, swollen, and shiny and later becomes purple, necrotic, and prone to bleeding. Additionally, poorly formed soft teeth are prone to infection. Musculoskeletal disease frequently presents in children. Hemorrhage can be intramuscular, intra-articular, or subperiosteal, leading to pain and pseudoparalysis. Bowing of the long bones, depression of the sternum, and swelling of the costochondral junctions are present on physical examination. Radiographic findings include a transverse metaphyseal radiolucent band (scurvy line or Trummerfeld zone), widening at the zone of calcification (white line of Frankel), a ring of increased density around the epiphysis (Wimberger ring), and metaphyseal spurs with marginal fractures (Pelkan spurs). Reports exist of conjunctival, intraocular, intracerebral, and gastrointestinal bleeding.
Other indications
Daily need increases in patients with conditions like gingivitis, asthma, glaucoma, collagen disorders, heatstroke, arthritis, infections (pneumonia, sinusitis, rheumatic fever), and chronic illnesses. Hemovascular disorders, burns, and delayed wound healing are causes for an increase in the daily intake.
Mechanism of Action
Absorption is through an energy-dependent process that has two mechanisms: simple diffusion and active transport. Two transporters are involved: SVCTs (sodium-dependent vitaminC transporters) and hexose transporters. The site for absorption isthe distal small intestine and is regulated by renal excretion. Usual dietary doses of up to 100 mg/day are almost completely absorbed. The highest ascorbic acid concentrations are in the pituitary gland, the adrenal gland, the brain, leukocytes, and the eyes.
Ascorbic acid functions as a cofactor, enzyme complement, co-substrate, and a powerful anti-oxidant in various reactions and metabolic processes. It also stabilizes vitamin E and folic acid and enhances iron absorption. It neutralizes free radicals and toxins as well as attenuates inflammatory response, including sepsis syndrome.
Administration
Usually administered orally,the drug may be administered intramuscularly, intravenously (IV), or subcutaneously whenmalabsorptionis suspected. ForIVinjection,minimize adverse reactions bydiluting the drug with normal saline or glucose.
The average protective adult dose of vitamin C is 70 to 150 mg daily. Increase the dose to 300 mg to 1 g dailywhen scurvy is present.
Adverse Effects
Adverse effects include headaches, flushing, nausea or vomiting, and dizziness (IV use). There are reports of migraine headaches with a daily dose of 6 g.
Significant amounts of vitamin C can increase the risk of kidney stones and elevate uric acid and oxalate becauseit acidifies the urine.
Contraindications
Vitamin C supplementation is contraindicated in blood disorders like thalassemia, G6PD deficiency, sickle cell disease, and hemochromatosis. Avoid taking supplements immediately before or following angioplasty. Diabetic patients should take vitamin C supplements with care as it raises blood sugar levels.
Vitamin C should be used cautiously in oxalate nephropathy or nephrolithiasis as acidification by ascorbic acid increases the chances of precipitation of cysteine, urate, and oxalate stones.
Monitoring
Scurvy is largely a clinical diagnosis. Serum ascorbic acid levels may be measured (greater than 11 micromoles/L), but this typically reflects recent dietary intake. Measurement of leukocyte ascorbic acid levels tends to be more accurate, but testing is not widely available. Normochromic normocytic anemia is common due to blood loss, folate deficiency, and iron deficiency.[6][7][8]
Test dichlorophenolindophenol to measure vitamin C level in urine and serum/plasma and high-performance liquid chromatography (HPLC) to measure storage level in lymphocytes and tissues.
The recommended daily intake of vitamin C is 40 to 120 mg, depending on age and gender.
Scurvy is treated with ascorbic acid 100 to 300 mg daily until symptoms remit. Clinical improvement is noted within the first 1 to 2 weeks, with a resolution of fatigue, joint swelling, ecchymoses, andgingivahealing. Complete recovery frequently occurs within three months.
Toxicity
Vitamin C (in grams) can give false negative stool guaiac results and is rarely associated with fatal cardiac arrhythmias in patients with iron overload.
Enhancing Healthcare Team Outcomes
Almost anyclinician, including the nurse practitioner, can prescribe vitamin C. However, unless there is a deficiency, the emphasis should be on eating a healthy diet that consists of fruits and veggies. Supplements of vitamin C are relatively safe but can be expensive in the long run. Plus, because there is no oversight on supplements, product quality can be an issue. There is very little good evidence to supportusing vitamin C to prevent most chronic disorders like heart disease, stroke, diabetes, or cancer.[4]
Whether prescribed by the clinician or taken as an OTC supplement, the entire interprofessional healthcare team, including all clinicians, nursing staff, and pharmacist, should know that the patient is taking vitamin C and be able to offer counsel, signs of deficiency and/or excessive intake, and offer counsel on how to optimize the use of this vitamin to achieve optimal outcomes. [Level5]
References
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Fenech M, Amaya I, Valpuesta V, Botella MA. Vitamin C Content in Fruits: Biosynthesis and Regulation. Front Plant Sci. 2018;9:2006. [PMC free article: PMC6353827] [PubMed: 30733729]
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Khalife R, Grieco A, Khamisa K, Tinmouh A, McCudden C, Saidenberg E. Scurvy, an old story in a new time: The hematologist's experience. Blood Cells Mol Dis. 2019 May;76:40-44. [PubMed: 30704850]
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Blaszczak W, Barczak W, Masternak J, Kopczyński P, Zhitkovich A, Rubiś B. Vitamin C as a Modulator of the Response to Cancer Therapy. Molecules. 2019 Jan 28;24(3) [PMC free article: PMC6384696] [PubMed: 30695991]
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Ashor AW, Brown R, Keenan PD, Willis ND, Siervo M, Mathers JC. Limited evidence for a beneficial effect of vitamin C supplementation on biomarkers of cardiovascular diseases: an umbrella review of systematic reviews and meta-analyses. Nutr Res. 2019 Jan;61:1-12. [PubMed: 30683434]
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de Carvalho Melo-Cavalcante AA, da Rocha Sousa L, Alencar MVOB, de Oliveira Santos JV, da Mata AMO, Paz MFCJ, de Carvalho RM, Nunes NMF, Islam MT, Mendes AN, Gonçalves JCR, da Silva FCC, Ferreira PMP, de Castro E Sousaa JM. Retinol palmitate and ascorbic acid: Role in oncological prevention and therapy. Biomed Pharmacother. 2019 Jan;109:1394-1405. [PubMed: 30551390]
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Zhan X, Zhu Z, Sun DW. Effects of pretreatments on quality attributes of long-term deep frozen storage of vegetables: a review. Crit Rev Food Sci Nutr. 2019;59(5):743-757. [PubMed: 30595028]
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Langlois PL, Manzanares W, Adhikari NKJ, Lamontagne F, Stoppe C, Hill A, Heyland DK. Vitamin C Administration to the Critically Ill: A Systematic Review and Meta-Analysis. JPEN J Parenter Enteral Nutr. 2019 Mar;43(3):335-346. [PubMed: 30452091]
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González-Fuentes J, Selva J, Moya C, Castro-Vázquez L, Lozano MV, Marcos P, Plaza-Oliver M, Rodríguez-Robledo V, Santander-Ortega MJ, Villaseca-González N, Arroyo-Jimenez MM. Neuroprotective Natural Molecules, From Food to Brain. Front Neurosci. 2018;12:721. [PMC free article: PMC6206709] [PubMed: 30405328]
Disclosure: Muhammad Abdullah declares no relevant financial relationships with ineligible companies.
Disclosure: Radia Jamil declares no relevant financial relationships with ineligible companies.
Disclosure: Fibi Attia declares no relevant financial relationships with ineligible companies.
