Ascorbic Acid (Vitamin C) Injection
Ascorbic acid is a water-soluble vitamin found in plants like citrus fruits and peppers. When isolated, it resembles a white or yellowish powder with an acidic taste. When exposed to air and light the color gradually darkens. In its dry state the product is relatively stable, but in solution it quickly oxidizes. Ascorbic acid is a free radical, or a scavenger of oxygen species, and it plays a role in oxidation-reduction reactions. The product is a cofactor for enzymes involved in the biosynthesis of collagen, carnitine, and neurotransmitters. Humans cannot synthesize ascorbic acid endogenously and must receive it through diet; a lack of intake leads to scurvy. Vitamin C is typically consumed as a nutritional supplement or an adjunct treatment of idiopathic methemoglobinemia and as a participant in the treatment of chronic iron toxicity. Ascorbic acid has been used to treat the common cold, gum infections, acne, depression, infertility, and cancer, though these claims have not been proven and vitamin C is not recommended for these purposes. Ascorbic acid received FDA approval in 1939.
Ascorbic acid supports collagen formation and tissue repair, and when reverse oxidized, it becomes dehydroascorbic acid. Both forms are involved in oxidation-reduction reactions. Vitamin C also contributes to the metabolism of tyrosine, carbohydrates, norepinephrine, histamine, and phenylalanine. It contributes vitally to the biosynthesis of corticosteroids and aldosterone, proteins, neuropeptides, and carnitine, also the conversion of cholesterol to bile acids, blood vessel maintenance, and cellular respiration. Vitamin C may activate white blood cells and thereby promote resistance to infection. It also supports the production of interferon and the regulation of the inflammatory process. It reduces iron in the intestine to allow absorption, transfers iron from plasma transferrin to liver ferritin, and regulates iron distribution and storage by preventing oxidation. Ascorbic acid also contributes to the treatment of chronic iron toxicity, and may have a role in the regeneration of other biological antioxidants such as glutathione and α-tocopherol to their active state.
In the absence of vitamin C, collagen formation is impaired due to a deficiency in the hydroxylation of procollagen and collagen. Non-hydroxylated collagen is unstable, and the normal processes of tissue repair cannot occur. This results in the various features of scurvy including capillary fragility manifested as hemorrhagic processes, bony abnormalities and delayed wound healing.
Other than scurvy, the use of vitamin C in the prevention and treatment of diseases is unclear. Further study is needed to recommend vitamin C therapy for the following ailments, but recent data suggest a role for vitamin C in the address of: the prevention of coronary heart disease; diabetes mellitus management; reducing stroke risk; management of atherosclerosis; osteoporosis prevention; reducing Alzheimer disease risk in combination with vitamin E; and cataract prevention. An exogenous source of ascorbic acid is required by humans for collagen formation and tissue repair.
Vitamin C may be taken orally or administered by intramuscular, subcutaneous, or intravenous injection. Foods and supplements offer similar bioavailabilities, though the bioavailability of vitamin C in foods is easily degraded with cooking, processing, or the addition of preservatives such as sodium bicarbonate. Approximately 70 to 90% of the typical dietary intake of ascorbic acid (30—180 mg/day) is absorbed, although absorption falls below 50% with doses above 1 g/day or in patients with GI disease. The biological half-life of the product varies between 8 and 40 days and is inversely related to body stores. The body typically stores 1.5 g of ascorbic acid, with a daily turnover of 30—45 mg. Total body stores of < 300 mg and 3—5 months of deficient vitamin C intake are associated with scurvy. High levels of ascorbate are maintained in the pituitary and adrenal glands, leukocytes, eye tissues, and brain. Vitamin C crosses the placenta and enters into breast milk.
Most ascorbic acid is reversibly oxidized to dehydroascorbic acid. The remainder is metabolized into inactive metabolites which are excreted in the urine. Unmetabolized ascorbate is not excreted with normal dietary intake, but increases proportionately with higher intake. When body stores become saturated, excess ascorbic acid is excreted unchanged in the urine and can indicated nutritional status via an ascorbic acid saturation test. Unabsorbed ascorbate from large oral does is degraded in the intestine, which may contribute to diarrhea and intestinal discomfort.
Intravenous Administration: Dilute in a compatible diluent prior to administration. Compatible diluents include Dextrose 5%, Dextrose 10%, 0.9% Sodium Chloride (Normal Saline or NS), 0.45% Sodium Chloride (half-Normal Saline), Lactated Ringer's (LR), Dextrose/Saline combinations or Dextrose/LR solutions. For intermittent IV infusion: Add to a large volume of diluent and infuse slowly (manufacturer recommendations). A faster rate of infusion and less diluent have been used in clinical trials. A pharmacokinetic modeling study reported the administration of intravenous vitamin C (doses up to 1.25 gram IV) at a rate of 250 mg/min IV to healthy volunteers.13 Another study reported the infusion of 3 g of vitamin C infused IV over 10 minutes (rate: 300 mg/min IV) without deleterious effects on monitoring parameters such as the ECG.14 For continuous IV infusion: When used for the reduction of fluid resuscitation requirements in severely burned patients, a 25 mg/mL concentration was compounded in LR solution and administered at a rate of 66 mg/kg/hr.
False negatives may occur if ascorbic acid is ingested 48—72 hours before amine-dependent stool occult blood tests.
Excessive regular doses of ascorbic acid can increase the metabolism of the product, which can lead to scurvy when normal or lower levels are resumed. Large doses can also generate oxalate stones in the urinary tract in patients with a history of nephrolithiasis, hyperoxaluria, or oxalosis.
In some patients with G6PD deficiency (glucose-6-phosphate dehydrogenase deficiency), large IV or oral doses of ascorbic acid have caused hemolytic anemia.
High doses of ascorbic acid may interfere with urinary glucose determinations made via the glucose oxidase method. Diabetes mellitus patients should recognize the possibility of false test results.
Ascorbic acid may elevate the risk of iron toxicity in hemochromatosis patients; these patients should limit their intake of ascorbic acid to no more than 500 mg/day. In rare cases, ingestion of large quantities of ascorbic acid have contributes to fatal cardiac arrhythmias in patients with iron overload.
Patients with anemia may experience decreased iron absorption during high dose therapy. High doses of ascorbic acid may also precipitate a crisis in patients with sickle cell anemia.
Vitamin C is classified as pregnancy category C. Umbilical cord blood concentrations are 2 to 4 times higher than those of maternal plasma levels. Normal daily intake of ascorbic acid is not associated with adverse effects for pregnant patients. The use of ascorbic acid in excess of the recommended dietary allowance during normal pregnancy should be avoided unless potential benefits in a specific case outweigh the hazards involved.
Ascorbic acid, vitamin C is distributed into breast milk. When kept within the recommended daily intake for lactating women, the product is considered safe. In mothers not taking vitamin C supplements, vitamin C in human milk in the first 6 months of lactation varies between 34 and 83 mg/L. In mothers taking vitamin C supplements ranging from 45 to > 1,000 mg/day, the content in human milk varies between 45 and 115 mg/L.17. If a breast-feeding infant experiences an adverse effect related to a drug administered to the mother, healthcare providers should report the adverse effect to the FDA.
Ascorbic acid is necessary for many functions, including iron metabolism. The absorption of nonheme iron from the intestinal tract requires the iron to exist in its reduced form. (Heme iron from meat products appears to be absorbed intact.) Ascorbic acid can enhance the absorption of oral iron, however, the increase is limited to about 10% and only occurs with doses of ascorbic acid of 500 mg or greater. Healthy individuals usually absorb iron supplements adequately from the GI tract, but some patients may benefit from receiving ascorbic acid with each oral iron dose.
Patients should be advised not to take ascorbic acid supplements along with deferoxamine chelation therapy unless the supplements are prescribed by a doctor. Patients with iron overload usually become vitamin C deficient, likely because the iron oxidizes the vitamin. Vitamin C can be a beneficial adjunct in iron chelation therapy. As an adjuvant, vitamin C (in doses up to 200 mg/day for adults, 50 mg/day in children < 10 years of age or 100 mg/day in older children) may be given in divided doses, starting after an initial month of regular treatment with deferoxamine. At the same time, higher doses of ascorbic acid can facilitate iron deposition, particularly in the heart tissue, causing cardiac decompensation. In patients with severe chronic iron overload, the use of deferoxamine with more than 500 mg/day PO of vitamin C has lead to impaired cardiac function; the dysfunction was reversed when vitamin C was discontinued. Vitamin C supplements should not be given concurrently with deferoxamine in patients with heart failure. In other patients, supplementation should not be started until one month of regular treatment with deferoxamine, and should be given only to patients receiving regular deferoxamine treatments. Vitamin C doses should not exceed 200 mg/day for adults, 50 mg/day for children under ten, or 100 mg/day in older children, and should be given in divided doses. All patients should be monitored for decreased cardiac function.
Large doses of ascorbic acid can lead to oxalate, urate, or cystine renal stones causing renal tubular obstruction, characterized by back pain. Also, hyperoxaluria develops in 5% of patients taking large doses. Patients with renal disease or a history of nephrolithiasis, and those on hemodialysis are at increased risk.
Ascorbic acid is generally nontoxic but may cause flushing, headache, nausea/vomiting, and abdominal cramps or diarrhea from high doses. Dizziness and faintness can result from rapid IV administration.
After receiving large IV or oral doses of ascorbic acid, some patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency experience hemolytic anemia. In rare cases, patients with sickle cell disease experience a crisis because of decreased blood pH.
Excessive use of chewable ascorbic acid can lead to the breakdown of dental enamel.