Vitamin C + Vitamin D3 + Folic acid

Approved Indications:

• Vitamin C (Ascorbic Acid): Prevention and treatment of scurvy and vitamin C deficiency; support for wound healing; enhancement of iron absorption.
• Vitamin D₃ (Cholecalciferol): Prevention and treatment of vitamin D deficiency; management of rickets and osteomalacia; adjunct in osteoporosis; maintenance of serum 25‑hydroxyvitamin D levels.
• Folic Acid (Vitamin B₉): Treatment and prevention of folate-deficiency anemia; prevention of neural tube defects during pregnancy; support of erythropoiesis.

Clinically Accepted Off‑label Uses:

• Immune support (combination boosts antioxidant defense and immune function).
• Support in chronic fatigue, frequent infections, or poor nutritional status.
• Adjunctive supplementation in elderly or post‑menopausal women (bone, hematologic, immune health).
• Pregnancy supplementation to support maternal and fetal health: folic acid for neural tube closure, vitamin D₃ for bone development, vitamin C for iron absorption.

Adults:

• Vitamin C: 75–90 mg/day (RDA); therapeutic/supportive doses up to 500–1000 mg/day.
• Vitamin D₃: 600–800 IU/day (RDA); higher doses (1,000–4,000 IU/day) for documented deficiency or osteoporosis support.
• Folic Acid: 400 µg/day standard; up to 1,000 µg/day in pregnancy or deficiency.

Combination Tablet (once-daily):

• Common formulation: Vitamin C 250 mg, Vitamin D₃ 1,000 IU (25 µg), Folic Acid 400 µg.

Elderly (≥65 years):

• Same dosing; consider higher vitamin D₃ (e.g., 2,000 IU/day) per bone health needs and serum 25(OH)D levels.

Pediatrics:

• Combination not routinely used in young children.
• Individual RDAs: Vitamin C 15–75 mg/day; Vitamin D₃ 400 IU/day; Folic Acid 150–300 µg/day.

Pregnancy & Lactation:

• Vitamin C: ~85 mg/day; therapeutic supplement up to 500 mg/day.
• Vitamin D₃: 600–800 IU/day; higher doses (up to 4,000 IU/day) for deficiency.
• Folic Acid: 400–800 µg/day, up to 1,000 µg/day to prevent neural tube defects.

Renal Impairment:

• Use caution with high-dose vitamin C (>1 g/day) due to oxalate risk; adjust based on renal function.
• Vitamin D₃ dose adjustment may be required in severe CKD (monitor calcium, phosphorus).

Hepatic Impairment:

• No routine adjustment; monitor liver function if using high-dose vitamin D₃ (rare hepatotoxic potential).

Administration Tips:

• Oral dosing with water; can be taken with or without food (vitamin D absorption improved with fat-containing food).
• Maintain consistent daily intake.
• Duration varies: maintenance vs. therapeutic dosing, often several weeks to months depending on deficiency correction.

• Vitamin C acts as a potent antioxidant, supports collagen synthesis (via hydroxylation of proline/lysine), enhances non-heme iron absorption (reducing Fe³⁺ to Fe²⁺), and supports immune cell function.
• Vitamin D₃ is converted to calcitriol (1,25-dihydroxyvitamin D), which binds the vitamin D receptor to promote intestinal absorption of calcium and phosphorus, regulate bone mineralization, and modulate immune and muscle function.
• Folic Acid is converted to tetrahydrofolate cofactors essential for one-carbon transfers in purine and thymidylate synthesis, red blood cell maturation, and DNA methylation.

Together, the combination supports antioxidant defense, hematopoiesis, bone health, immune support, and fetal development.

• Vitamin C:
• Absorption: Active transport in small intestine; saturable above ~200 mg.
• Peak: ~1–2 hours post-dose.
• Half-life: Short (8–40 minutes at physiologic doses; longer at high doses).
• Excretion: Renal; as ascorbate or oxalate.
• Vitamin D₃:
• Absorption: Fat-soluble; improved with dietary fat.
• Peak: Several hours after ingestion.
• Half-life: ~15 days for 25-hydroxyvitamin D; longer for storage form.
• Metabolism: Converted in liver to 25(OH)D, then kidney to 1,25(OH)₂D.
• Excretion: Bile/feces and renal.
• Folic Acid:
• Absorption: Proximal small intestine; ~85% bioavailability.
• Peak: ~1 hour.
• Half-life: ~85 hours.
• Excretion: Renal; metabolites excreted via urine.

• Pregnancy: All three are regarded as safe and essential. Folic acid critically reduces neural tube defect risk; vitamin D₃ supports fetal bone growth; vitamin C supports iron absorption and maternal immune health. Generally recommended at RDA or pregnancy-specific doses.
• Lactation: All are excreted into breast milk at low levels. Standard supplementation is considered safe. High-dose vitamin C (>1,000 mg/day) may cause infant diarrhea or discomfort.
• Caution: Remain within recommended ranges unless higher dosing is medically indicated.

• Vitamin C: Water-soluble vitamin; antioxidant cofactor.
• Vitamin D₃: Fat-soluble vitamin; hormone precursor.
• Folic Acid: Water-soluble B-vitamin; one-carbon metabolism coenzyme.

Combination class: Multivitamin / Nutritional Supplement.

• Known hypersensitivity to any component.
• History of oxalate kidney stones or oxaluria (vitamin C high doses).
• Hypercalcemia or sarcoidosis (vitamin D₃ may exacerbate).
• Iron overload disorders (combination may boost iron absorption via vitamin C).
• Severe renal failure or dialysis patients (risk of oxalate/calcium accumulation).

• Renal stone risk: High-dose vitamin C increases oxalate; ensure adequate hydration.
• Hypercalcemia risk: Vitamin D₃ may elevate calcium; monitor calcium/phosphate in susceptible patients.
• Vitamin D toxicity: Signs include hypercalcemia, nausea, weakness—rare at recommended doses.
• Folate masking B₁₂ deficiency: High-dose folic acid alone may mask cobalamin deficiency; assess B₁₂ status if anemia persists.
• G6PD deficiency: IV vitamin C at high doses may induce hemolysis.
• Monitoring: Serum calcium, renal function, and vitamin levels when using high-dose or long-term therapy.

Common:

• GI: Nausea, diarrhea, abdominal cramps (dose-dependent).
• CNS: Headache, mild fatigue with vitamin D₃ initiation.

Less Common:

• Skin rash or flushing.
• Hypercalcemia symptoms (polydipsia, polyuria, weakness).

Serious (Rare):

• Nephrolithiasis from oxalate or calcium.
• Vitamin D₃ overdose: hypercalcemia, cardiac arrhythmias, nephrocalcinosis.
• Hemolysis in G6PD-deficient individuals (with high IV vitamin C).

Timing: GI symptoms within hours; hypercalcemia and nephrotoxicity over weeks of excessive dosing.

• Vitamin C: Increases iron absorption; may raise aluminum absorption from antacids; high-dose may interfere with glucose readings.
• Vitamin D₃: Concurrent thiazide diuretics increase hypercalcemia risk; corticosteroids may reduce vitamin D efficacy; calcitriol and digoxin potentiation risk.
• Folic Acid: Interferes with methotrexate activity (antifolate); anticonvulsants (e.g., phenytoin, carbamazepine) reduce folate; trimethoprim-sulfamethoxazole lowers folate levels.
• Alcohol: Chronic intake reduces absorption/utilization of all three.

No significant involvement of CYP450 enzyme systems.

• Prenatal health: Continued global endorsement of folic acid (400–800 µg/day) and vitamin D₃ supplementation (600–800 IU, or up to 2,000–4,000 IU if deficient) in pregnancy by WHO and national guidelines.
• Bone health: Recent osteoporosis guidelines recommend vitamin D₃ supplementation (800–2,000 IU/day) with calcium in older adults.
• Trials in COVID-19 and sepsis: Vitamin C and D₃ studied as immunomodulatory agents; no regulatory indication changes but supportive research ongoing.
• No new contraindications or dosage restrictions have been issued recently.

• Tablets/Chewable/Effervescent: Store at 20–25 °C (68–77 °F), excursions allowed between 15–30 °C (59–86 °F); protect from moisture and direct light.
• Syrup: Store sealed in a dry, cool place below 25 °C; avoid freezing.
• Reconstitution: Not applicable.
• Handling: Do not freeze; keep in original container to preserve stability.
• Safety: Keep out of reach of children; clearly label to prevent accidental overdose.