Vitamin C (Ascorbic Acid)


Article Author:
Muhammad Abdullah
Radia Jamil


Article Editor:
Fibi Attia


Editors In Chief:
Sherri Murrell


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
10/21/2019 12:07:53 PM

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 it is strictly obtained 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 the 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. Persons at risk for inadequate intake of vitamin include patients in the following groups:

  • The elderly
  • Those with alcoholism, 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 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 a 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 is frequently seen 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 noted 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). Conjunctival, intraocular, intracerebral, and gastrointestinal bleeding have been reported.

Other indications

Daily need increases in patients with conditions like gingivitis, asthma, glaucoma, collagen disorders, heat stroke, 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 vitamin C transporters) and hexose transporters. The site for absorption is the distal small intestine and is regulated by renal excretion. Usual dietary doses of up to 100 mg/day are almost completely absorbed. The greatest concentrations of ascorbic acid are found in the pituitary gland, the adrenal gland, the brain, leukocytes, and eyes.

Ascorbic acid functions as the cofactor, enzyme complement, co-substrate and a very strong anti-oxidant in a variety of 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 when malabsorption is suspected. For IV injection, minimize adverse reactions by diluting 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 daily when scurvy is present.

Adverse Effects

Adverse effects include headaches, flushing, nausea or vomiting, and dizziness (IV use). Migraine headaches have been reported 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 because it acidifies 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, and gingiva healing. Complete recovery frequently occurs within 3 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 any healthcare provider 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, one never knows if the product is fake or counterfeit. There is very little good evidence to support the use of vitamin C for prevention of most chronic disorders like heart disease, stroke, diabetes or cancer.[4]


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Vitamin C (Ascorbic Acid) - Questions

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Which contains the highest amount of vitamin C?



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A 65-year-old female presents with malaise and easy bruising. On exam, there is evident gum disease and several loose teeth. Labs reveal that she is severely vitamin C deficient. Vitamin C deficiency results in improper collagen synthesis that is responsible for this patient's symptoms. What is the role of vitamin C in collagen synthesis?



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Which is not a function of vitamin C?



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Which of the following is not true of vitamin C?



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Which food is lowest in vitamin C?



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A 17-year-old patient presents to the healthcare provider with complaints of fatigue, depression, amenorrhea for the last three months. She does not use tobacco, alcohol, or illicit drugs. Her family history is positive for a maternal aunt with major depressive disorder. On physical examination, the patient is thin with pale conjunctivae. Her gums bleed easily and have several poorly healed bruises, which she says have been present for several weeks. She has a BMI of 17 kg/m2. Which of the following is true about the most likely nutrient deficiency causing her clinical presentation?



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Which of the following vitamins does the human body not store?



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A depressed patient presents with a complaint of indigestion, nausea, vomiting, diarrhea, fatigue, and insomnia. Which of the following is most likely correct?



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A 65-year-old male presents to the healthcare provider for a routine health evaluation. He had an episode of diarrhea five days ago, which resolved on its own. The patient denies epigastric pain, weight loss, or constipation. He is a non-smoker and does not use alcohol or illicit drugs. The patient has a past medical history of hypertension controlled with lisinopril and dietary restrictions. His surgical history is positive for an appendectomy at the age of 37, and his family history is positive for a father with colon cancer diagnosed at age 75. The patient is very health conscious and proudly tells the provider that he exercises for two hours every day, eats a well-balanced diet along with nutritional supplements. On examination, his vitals are normal, and the cardiopulmonary and abdominal examinations are insignificant. A stool guaiac test for colon cancer screening comes back negative. Due to high clinical suspicion, the provider repeats the test, which comes back positive. Colonoscopy confirms the presence of a mass consistent with carcinoma. What is the most likely cause of the first stool guaiac test result?



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Vitamin C (Ascorbic Acid) - References

References

Fenech M,Amaya I,Valpuesta V,Botella MA, Vitamin C Content in Fruits: Biosynthesis and Regulation. Frontiers in plant science. 2018;     [PubMed]
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, molecules     [PubMed]
Blaszczak W,Barczak W,Masternak J,Kopczyński P,Zhitkovich A,Rubiś B, Vitamin C as a Modulator of the Response to Cancer Therapy. Molecules (Basel, Switzerland). 2019 Jan 28;     [PubMed]
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. Nutrition research (New York, N.Y.). 2019 Jan;     [PubMed]
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. Biomedicine     [PubMed]
Zhan X,Zhu Z,Sun DW, Effects of pretreatments on quality attributes of long-term deep frozen storage of vegetables: a review. Critical reviews in food science and nutrition. 2018 Dec 30;     [PubMed]
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. Journal of parenteral and enteral nutrition. 2018 Nov 19;     [PubMed]
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. Frontiers in neuroscience. 2018;     [PubMed]

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