ASCORBIC ACID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ASCORBIC ACID (ASCORBIC ACID).
Ascorbic acid is a water-soluble vitamin that acts as an electron donor for several enzymatic reactions, including collagen synthesis, neurotransmitter synthesis, and carnitine synthesis. It also functions as a potent antioxidant, protecting cells from oxidative damage.
| Metabolism | Primarily metabolized in the liver via oxidation to dehydroascorbic acid, which is further converted to oxalate, threonate, and ascorbate-2-sulfate. Renal excretion of metabolites and unchanged drug. |
| Excretion | Renal: 100% as unchanged drug and metabolites; tubular reabsorption is saturable; at high doses, excretion increases proportionally. Fecal: minimal. |
| Half-life | Terminal half-life: 10-20 hours in healthy adults; prolonged in renal impairment. Clinical context: doses >200 mg/day lead to renal elimination of unchanged ascorbate, reducing half-life. |
| Protein binding | 25-30% bound, primarily to albumin. |
| Volume of Distribution | 0.14-0.6 L/kg (overall), with highest concentrations in adrenal glands, pituitary, and leukocytes. Vd increases in inflammatory states. |
| Bioavailability | Oral: 70-90% at doses up to 200 mg; decreases to 50% at 500 mg and 20% at 1250 mg due to saturable intestinal absorption. Intravenous: 100%. |
| Onset of Action | Oral: clinical effect (reversal of deficiency symptoms) begins within 24-48 hours. Intravenous: immediate for acute deficiency. Topical: not applicable for systemic effect. |
| Duration of Action | Duration: 4-6 weeks after discontinuation in deficiency states; depends on body stores. Clinical notes: stores are depleted in 4-12 weeks without intake. |
Oral: 100-200 mg daily for prevention; 500-1000 mg daily for deficiency. IV/IM: 100-250 mg once daily for deficiency; higher doses (e.g., 1-3 g daily) for scurvy.
| Dosage form | SOLUTION |
| Renal impairment | No specific dose adjustment for GFR; use caution in severe renal impairment (eGFR <30 mL/min/1.73 m²) due to oxalate accumulation; avoid high doses (>1 g/day) in chronic kidney disease. |
| Liver impairment | No specific Child-Pugh based dose adjustment; monitor for potential oxalate nephropathy in severe hepatic impairment. |
| Pediatric use | Infants: 30-50 mg/day; Children 1-3 years: 15 mg/day; 4-8 years: 25 mg/day; 9-13 years: 45 mg/day; 14-18 years: 65-75 mg/day. For deficiency, 100-300 mg/day divided. |
| Geriatric use | No specific dose adjustment; use lowest effective dose due to potential renal impairment; avoid doses >1 g/day to prevent oxalate stones. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ASCORBIC ACID (ASCORBIC ACID).
| Breastfeeding | Ascorbic acid is excreted into breast milk; concentrations in milk correspond to maternal intake. The M/P ratio is approximately 1.0. The dietary allowance for lactation is 120 mg/day. Excessive maternal intake may lead to diarrhea in infants. No adverse effects reported at recommended doses. |
| Teratogenic Risk | Ascorbic acid (vitamin C) is generally considered safe during pregnancy at recommended dietary allowances. High doses (e.g., >1000 mg/day) have not been associated with teratogenicity in human studies, but animal studies show no evidence of fetal harm. No trimester-specific risks; however, megadoses near delivery may cause neonatal scurvy due to metabolic withdrawal. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to ascorbic acid","Patients with known oxalate kidney stones (relative contraindication)","Concurrent use with deferoxamine in iron overload (due to increased iron absorption)"]
| Precautions | ["Caution in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolytic anemia","High doses may cause oxalate kidney stones","Interference with laboratory tests (e.g., glucose, bilirubin)","Use with caution in patients with iron overload disorders"] |
| Food/Dietary | Vitamin C enhances non-heme iron absorption from plant foods; avoid taking with dairy or calcium-rich foods within 1 hour. Do not drink large amounts of grapefruit juice concurrently. Cooking destroys vitamin C; take supplements with food but avoid excessive heat exposure. Alcohol consumption increases urinary excretion of vitamin C. |
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| Fetal Monitoring | No specific monitoring required. For high-dose therapy (>1000 mg/day), monitor for maternal gastrointestinal side effects (diarrhea, cramps) and renal oxalate stone formation. Fetal monitoring not indicated. |
| Fertility Effects | No evidence of adverse effects on fertility in humans. Ascorbic acid is essential for reproductive health; deficiency may impair fertility, but supplementation at recommended doses does not enhance fertility. |
| Clinical Pearls | Ascorbic acid (vitamin C) is essential for collagen synthesis and acts as an antioxidant. High-dose IV ascorbic acid is used as adjunctive therapy in sepsis and COVID-19, but oral absorption is saturable (doses >200 mg have decreased bioavailability). Monitoring serum uric acid is recommended in patients with gout due to potential oxalate crystal formation. Co-administration with iron increases iron absorption, which can be beneficial in iron deficiency anemia but may cause hemosiderosis in patients with hemochromatosis. In G6PD deficiency, high doses may cause hemolysis. |
| Patient Advice | Do not exceed 2000 mg per day from all sources to avoid gastrointestinal distress and kidney stones. · Smoking and alcohol consumption increase vitamin C requirements; consult your doctor for appropriate dosing. · Take with food to reduce stomach upset; do not take with dairy products within 1 hour as calcium may impair absorption. · High doses may cause false-negative stool occult blood tests; inform your doctor of recent vitamin C intake. · If you have a history of kidney stones (especially oxalate stones) or G6PD deficiency, consult your doctor before taking high doses. |