Each chewable tablet contains: Vitamin C (as sodium sacorbate and ascorbic acid) 500 mg • Acerola 5 mg • Citrus Bioflavonoids (37% total bioflavonoids as hesperidin) 5 mg • Orange juice powder 100 mg. Other Ingredients: Xylitol, Sorbitol, Cellulose, Natural Flavors, Vegetable Source Stearic Acid, Vegetable Source Magnesium Stearate, Beta Carotene, Silica.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product C 500. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product C 500. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when acerola fruit is used orally and appropriately. Acerola fruit contains an average of 2000 mg vitamin C per 100 grams of fruit, although this content varies widely. Acerola fruit should be consumed in amounts that do not provide more vitamin C than the tolerable upper intake level (UL) of 2000 mg per day for adults (4844).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in amounts greater than found in foods.
LIKELY SAFE ...when used orally in amounts found in foods.
POSSIBLY SAFE ...when supplements are used orally and appropriately, short-term. Doses of up to 3 grams daily have been used with apparent safety for up to 3 months (37494,54850,94544,105275,105276).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods.
PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally in doses of up to 100 mg daily for 30 days in combination with diosmin.
Some evidence suggests that taking this combination may be associated with placental insufficiency when used during the third trimester of pregnancy; however, the combination does not seem to induce fetal abnormalities, retard fetal growth, increase the risk of intrauterine death, or affect birth weight. Also, when breastfeeding, this combination does not seem to affect infant growth or feeding (54970).
LIKELY SAFE ...when sweet orange juice or fruit is used orally in amounts commonly found in foods (1310,3340,15171,92309,114401).
POSSIBLY SAFE ...when the essential oil of sweet orange is inhaled as aromatherapy, short-term (35735,58060,90505,105455). There is insufficient reliable information available about the safety of sweet orange peel when used orally.
CHILDREN: LIKELY SAFE
when sweet orange juice or fruit is used orally in amounts commonly found in foods.
CHILDREN: POSSIBLY UNSAFE
when the sweet orange peel is used orally in excessive amounts.
There have been reports of intestinal colic, convulsions, and death in children given large amounts of sweet orange peel (11).
PREGNANCY AND LACTATION: LIKELY SAFE
when sweet orange juice or fruit is used orally in amounts commonly found in foods (1310,3340).
LIKELY SAFE ...when used orally, topically, intramuscularly, or intravenously and appropriately. Vitamin C is safe when taken orally in doses below the tolerable upper intake level (UL). Tell patients not to exceed the UL of 2000 mg daily (1959,4713,4714,4844). ...when used intravenously or intramuscularly and appropriately. Injectable vitamin C is an FDA-approved prescription product (15) and has been used with apparent safety in clinical trials up to 150 mg/kg daily for up to 4 days (114489) and up to 200 mg/kg daily for up to 2 days (114492).
POSSIBLY UNSAFE ...when used orally in excessive doses. Doses greater than the tolerable upper intake level (UL) of 2000 mg daily can significantly increase the risk of adverse effects such as osmotic diarrhea and gastrointestinal upset (4844).
CHILDREN: LIKELY SAFE
when used orally and appropriately (4844,10352,14443).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive amounts.
Tell patients not to use doses above the tolerable upper intake level (UL) of 400 mg daily for children ages 1 to 3 years, 650 mg daily for children 4 to 8 years, 1200 mg daily for children 9 to 13 years, and 1800 mg daily for adolescents 14 to 18 years. Higher doses can cause osmotic diarrhea and gastrointestinal upset (4844).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately (4844).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Tell patients over age 19 not to use doses exceeding the UL of 2000 mg daily when pregnant or breast-feeding and for those 14-18 years of age not to use doses exceeding 1800 mg daily when pregnant or breast-feeding. Higher doses can cause osmotic diarrhea and gastrointestinal upset. Large doses of vitamin C during pregnancy can also cause newborn scurvy (4844); avoid using.
Below is general information about the interactions of the known ingredients contained in the product C 500. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, the antioxidant effects of acerola might reduce the effectiveness of alkylating agents.
 Details
Acerola contains vitamin C, an antioxidant. There is concern that antioxidants might reduce the activity of chemotherapy drugs that generate free radicals, such as alkylating agents (391). In contrast, other researchers theorize that antioxidants might make alkylating chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.
|
Theoretically, concomitant use of acerola with aluminum salts might increase the amount of aluminum absorbed.
Details
Acerola contains vitamin C. It is thought that vitamin C chelates aluminum, keeping it in solution and available for absorption (10549,10550,10551). In people with normal renal function, urinary excretion of aluminum likely increases, making aluminum retention and toxicity unlikely (10549). However, patients with renal failure who take aluminum-containing compounds, such as phosphate binders, should avoid acerola in doses that provide more vitamin C than the recommended dietary allowances.
|
Theoretically, the antioxidant effects of acerola might reduce the effectiveness of antitumor antibiotics.
Details
Acerola contains vitamin C, an antioxidant. There is concern that antioxidants might reduce the activity of chemotherapy drugs that generate free radicals, such as antitumor antibiotics (391). In contrast, other researchers theorize that antioxidants might make antitumor antibiotic chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on antitumor antibiotic chemotherapy.
|
Theoretically, acerola might reduce the clearance of aspirin; however, its vitamin C content is likely too low to produce clinically significant effects.
Details
Acerola contains vitamin C. It has been suggested that acidification of the urine by vitamin C can decrease the urinary excretion of salicylates, increasing plasma salicylate levels (3046). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589). The vitamin C content of acerola is typically about 2000 mg per 100 grams. Thus, a clinically significant interaction between acerola and aspirin is unlikely.
|
Theoretically, concomitant use of acerola with estrogens might increase estrogenic effects.
Details
Acerola contains vitamin C. Increases in plasma estrogen levels of up to 55% have occurred under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products (129,130,11161). It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall (129,11161). When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. However, increases in plasma estrogen levels may occur when women who are deficient in vitamin C take supplements (11161).
|
Theoretically, acerola might reduce the effectiveness of warfarin; however, its vitamin C content is likely too low to produce clinically significant effects.
Details
Acerola contains vitamin C. High doses of vitamin C may reduce the response to warfarin, possibly by causing diarrhea and reducing warfarin absorption (11566). This occurred in two people who took up to 16 grams daily of vitamin C, and resulted in decreased prothrombin time (9804,9806). Lower doses of 5-10 grams daily of vitamin C can also reduce warfarin absorption, but this does not seem to be clinically significant (9805,9806,11566,11567). The vitamin C content of acerola is typically about 2000 mg per 100 grams. Thus, a clinically significant interaction between acerola and warfarin is unlikely.
|
Theoretically, hesperidin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Animal research suggests that hesperetin, a bioflavonoid aglycone derivative of hesperidin, may have antiplatelet activity (54822).
|
Theoretically, taking hesperidin with antihypertensive drugs might increase the risk of hypotension.
Details
|
Theoretically, hesperidin may decrease the levels and clinical effects of celiprolol.
Details
Animal research shows that concomitant use of hesperidin may reduce the plasma area under the curve of celiprolol by up to 75% (91760). This effect has not been reported in humans.
|
Theoretically, concomitant use with CNS depressants may cause additive sedative effects.
Details
|
Theoretically, hesperidin may increase the levels and clinical effects of diltiazem.
Details
Animal research suggests that hesperidin may enhance the bioavailability of diltiazem, increasing the plasma area under the curve of diltiazem by up to 65.3% (91761). This effect has not been reported in humans.
|
Theoretically, hesperidin might inhibit P-glycoprotein-mediated drug efflux and potentially increase levels of drugs that are substrates of P-glycoprotein.
Details
In vitro research shows that hesperidin can inhibit P-glycoprotein efflux (54908). This effect has not been reported in humans.
|
Theoretically, hesperidin might increase the levels and clinical effects of verapamil.
Details
Animal research suggests that hesperidin may enhance the bioavailability of verapamil, increasing the plasma area under the curve of verapamil by 96.8% (91762). This effect has not been reported in humans
|
Consuming sweet orange with celiprolol can decrease oral absorption of celiprolol.
Details
A pharmacokinetic study in healthy volunteers shows that celiprolol levels, after a single dose of 100 mg, are decreased by up to 90% in people who drink sweet orange juice 200 mL three times daily. It's not known if lower consumption of sweet orange juice will have the same effect. Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP) (12115,17603,17604). Recommend separating drug administration and consumption of sweet orange by at least 4 hours (17603,17604).
|
Consuming sweet orange juice with fexofenadine can decrease oral absorption of fexofenadine.
Details
Clinical research shows that coadministration of sweet orange juice 1200 mL decreases bioavailability of fexofenadine by about 72% (7046,17604). In an animal model, sweet orange juice decreased bioavailability of fexofenadine by 31% (17605). Fexofenadine manufacturer data indicates that concomitant administration of sweet orange juice and fexofenadine results in larger wheal and flare sizes in research models. This suggests that sweet orange reduces the clinical response to fexofenadine (17603). Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP) (7046). Recommend separating drug administration and consumption of sweet orange by at least 4 hours (17603,17604).
|
Consuming sweet orange juice with ivermectin can decrease the oral absorption of ivermectin.
Details
A pharmacokinetic study in healthy volunteers shows that taking ivermectin orally with sweet orange juice 750 mL over 4 hours reduces the bioavailability of ivermectin. This effect does not seem to be related to effects on P-glycoprotein. The effect on ivermectin is more pronounced in males compared to females (12154).
|
Consuming sweet orange juice can decrease oral absorption of OATP substrates. Separate administration by at least 4 hours.
Details
Clinical research shows that consuming sweet orange juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP (17603,17604). For example, sweet orange juice decreases bioavailability of fexofenadine, a substrate of OATP, by about 72% and of celiprolol, another OATP substrate, by up to 90% (7046,12115). Since sweet orange juice seems to affect OATP for a short time, recommend separating drug administration and consumption of sweet orange juice by at least 4 hours (17603,17604).
|
Sweet orange juice seems to modulate P-glycoprotein (P-gp), which might affect the blood levels of P-gp substrates.
Details
Animal and in vitro research suggest that orange juice extract inhibits drug efflux by P-gp, increasing absorption and levels of P-gp substrates (12116,15327). In contrast, pharmacokinetic research in humans shows that drinking large amounts of sweet orange juice decreases absorption and levels of the P-gp substrate celiprolol. This suggests that orange juice actually induces drug efflux by P-gp or affects drug levels by another mechanism such as inhibiting the gut drug transporter called organic anion transporting polypeptide (OATP) (7046,12115). Until more is known, sweet orange juice should be used cautiously in people taking P-gp substrates.
|
Consuming sweet orange juice with pravastatin can increase the absorption of pravastatin.
Details
A small pharmacokinetic study in healthy volunteers shows that consuming sweet orange juice 800 mL over 3 hours, including before, during, and after taking pravastatin 10 mg, increases pravastatin levels by about 149%, without affecting pravastatin elimination. Theoretically this effect might be due to modulation of organic anion transporting polypeptides (OATPs) by sweet orange juice (14348). Sweet orange juice does not seem to affect simvastatin levels, but it is not known if sweet orange affects any of the other statins.
|
Calcium-fortified sweet orange juice might reduce quinolone absorption.
Details
|
High-dose vitamin C might slightly prolong the clearance of acetaminophen.
Details
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases (6451). This effect is not likely to be clinically significant.
|
Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
Details
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.
|
Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Details
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption (10549,10550,10551,21556). In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely (10549). Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.
|
Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
Details
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.
|
Acidification of the urine by vitamin C might increase aspirin levels.
Details
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction is not clinically significant.
|
Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
Details
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046,4531). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.
|
Vitamin C might increase blood levels of estrogens.
Details
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products (129,130,11161). It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall (129,11161). When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements (11161). Monitor these patients for estrogen-related side effects.
|
Theoretically, vitamin C might decrease levels of fluphenazine.
Details
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started (11017). The mechanism is not known, and there is no further data to confirm this interaction.
|
Vitamin C can modestly reduce indinavir levels.
Details
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown (11300,93578).
|
Vitamin C can increase levothyroxine absorption.
Details
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH (102978).
|
Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
Details
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.
|
Acidification of the urine by vitamin C might increase salsalate levels.
Details
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046). However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.
|
High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Details
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption (11566). There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time (9804,9806). Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant (9805,9806,11566,11567). However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR) (90942). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.
|
Below is general information about the adverse effects of the known ingredients contained in the product C 500. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, acerola seems to be well tolerated.
However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Acerola has been linked with one case of anaphylaxis and one case of rectal obstruction.
Gastrointestinal ...Osmotic diarrhea and gastrointestinal upset have been reported with doses of vitamin C greater than the tolerable upper intake level (UL) of 2000 mg daily (4844). Theoretically this could occur with large doses of oral acerola. A case report describes rectal obstruction with mass consisting of partially digested acerola fruits in a 5-year-old child who had ingested an unknown quantity of fruits daily for 7 days. The child presented with vomiting, abdominal pain and distension, tenesmus, constipation, and dehydration, and required surgical disimpaction (93205).
Immunologic ...There is a case report of a 37 year old man who developed a pruritic rash, dyspnea, and tachycardia 5 minutes after drinking a mixture of apple and acerola juices. He had a history of hay fever, oral allergy symptoms with avocado, celery, walnut, and curry, and contact urticaria with latex, but tolerated apples and apple juice. IgE antibodies to acerola were identified in the patient's serum. Ultimately, cross-reactivity between a latex protein and acerola was determined (93206).
General ...Orally, hesperidin is generally well tolerated.
Dermatologic ...A case of recurrent allergic dermatitis was reported in a 70-year-old female with no known allergies who applied topical hesperidin methyl chalchone (94538).
Immunologic ...A case of recurrent allergic dermatitis was reported in a 70-year-old female with no known allergies who applied topical hesperidin methyl chalchone (94538).
General ...Orally, sweet orange juice or fruit seem to be well tolerated. Large amounts of sweet orange peel may be unsafe, especially for children. When inhaled, sweet orange essential oil seems to be generally well tolerated.
Gastrointestinal ...There have been reports of intestinal colic in children following ingestion of large amounts of sweet orange peel (11).
Neurologic/CNS ...There have been reports of convulsions in children following ingestion of large amounts of sweet orange peel (11).
General
...Orally, intravenously, and topically, vitamin C is well-tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, esophagitis, heartburn, headache, osmotic diarrhea, nausea, vomiting. Kidney stones have been reported in those prone to kidney stones. Adverse effects are more likely to occur at doses above the tolerable upper intake level of 2 grams daily.
Topically: Irritation and tingling.
Serious Adverse Effects (Rare):
Orally: There have been rare case reports of carotid inner wall thickening after large doses of vitamin C.
Intravenously: There have been case reports of hyperoxalosis and oxalate nephropathy following high-dose infusions of vitamin C.
Cardiovascular
...Evidence from population research has found that high doses of supplemental vitamin C might not be safe for some people.
In postmenopausal adults with diabetes, supplemental vitamin C intake in doses greater than 300 mg per day is associated with increased risk of cardiovascular mortality. However, dietary intake of vitamin C is not associated with this risk. Also, vitamin C intake is not associated with an increased risk of cardiovascular mortality in patients without diabetes (12498).
Oral supplementation with vitamin C has also been associated with an increased rate of carotid inner wall thickening in men. There is preliminary evidence that supplemental intake of vitamin C 500 mg daily for 18 months can cause a 2.5-fold increased rate of carotid inner wall thickening in non-smoking men and a 5-fold increased rate in men who smoked. The men in this study were 40-60 years old (1355). This effect was not associated with vitamin C from dietary sources (1355).
There is also some concern that vitamin C may increase the risk of hypertension in some patients. A meta-analysis of clinical research suggests that, in pregnant patients at risk of pre-eclampsia, oral intake of vitamin C along with vitamin E increases the risk of gestational hypertension (83450). Other clinical research shows that oral intake of vitamin C along with grape seed polyphenols can increase both systolic and diastolic blood pressure in hypertensive patients (13162). Three cases of transient hypotension and tachycardia during intravenous administration of vitamin C have also been reported (114490).
Dental ...Orally, vitamin C, particularly chewable tablets, has been associated with dental erosion (83484).
Dermatologic ...Topically, vitamin C might cause tingling or irritation at the site of application (6166). A liquid containing vitamin C 20%, red raspberry leaf cell culture extract 0.0005%, and vitamin E 1% (Antioxidant and Collagen Booster Serum, Max Biocare Pty Ltd.) has been reported to cause mild tingling and skin tightness (102355). It is unclear if these effects are due to vitamin C, the other ingredients, or the combination.
Gastrointestinal ...Orally, the adverse effects of vitamin C are dose-related and include nausea, vomiting, esophagitis, heartburn, abdominal cramps, gastrointestinal obstruction, and diarrhea. Doses greater than the tolerable upper intake level (UL) of 2000 mg per day can increase the risk of adverse effects such as osmotic diarrhea and severe gastrointestinal upset (3042,4844,96707,104450,114493,114490). Mineral forms of vitamin C, such as calcium ascorbate (Ester-C), seem to cause fewer gastrointestinal adverse effects than regular vitamin C (83358). In a case report, high dose intravenous vitamin C was associated with increased thirst (96709).
Genitourinary ...Orally, vitamin C may cause precipitation of urate, oxalate, or cysteine stones or drugs in the urinary tract (10356). Hyperoxaluria, hyperuricosuria, hematuria, and crystalluria have occurred in people taking 1 gram or more per day (3042,90943). Supplemental vitamin C over 250 mg daily has been associated with higher risk for kidney stones in males. There was no clear association found in females, but the analysis might not have been adequately powered to evaluate this outcome (104029). In people with a history of oxalate kidney stones, supplemental vitamin C 1 gram per day appears to increase kidney stone risk by 40% (12653). A case of hematuria, high urine oxalate excretion, and the presence of a ureteral stone has been reported for a 9-year-old male who had taken about 3 grams of vitamin C daily since 3 years of age. The condition resolved with cessation of vitamin C intake (90936).
Hematologic ...Prolonged use of large amounts of vitamin C can result in increased metabolism of vitamin C; subsequent reduction in vitamin C intake may precipitate the development of scurvy (15). In one case, a patient with septic shock and a large intraperitoneal hematoma developed moderate hemolysis and increased methemoglobin 12 hours after a high-dose vitamin C infusion. The patient received a blood transfusion and the hemolysis resolved spontaneously over 48 hours (112479).
Neurologic/CNS ...Orally, the adverse effects of vitamin C are dose-related and include fatigue, headache, insomnia, and sleepiness (3042,4844,83475,83476).
Renal ...Hyperoxalosis and oxalate nephropathy have been reported following high-dose infusions of vitamin C. Hyperoxalosis and acute kidney failure contributed to the death of a 76-year-old patient with metastatic adenocarcinoma of the lung who received 10 courses of intravenous infusions containing vitamins, including vitamin C and other supplements over a period of 1 month. Dosages of vitamin C were not specified but were presumed to be high-dose (106618). In another case, a 34-year-old patient with a history of kidney transplant and cerebral palsy was found unresponsive during outpatient treatment for a respiratory tract infection. The patient was intubated for acute hypoxemic respiratory failure, initiated on vasopressors, hydrocortisone, and antibacterial therapy, and received 16 doses of vitamin C 1.5 grams. Serum creatinine level peaked at greater than 3 times baseline and the patient required hemodialysis for oliguria and uncontrolled acidosis. Kidney biopsy revealed oxalate nephropathy with concomitant drug-induced interstitial nephritis (106625). In another case, a 41-year-old patient with a history of kidney transplant presented with fever, nausea, and decreased urine output 4 days after receiving intravenous vitamin C 7 grams for urothelial carcinoma. Serum creatinine levels increased from 1.7 mg/dL to 7.3 mg/dL over those 4 days, and hemodialysis was initiated 3 days after admission due to anuria. Renal biopsy confirmed the diagnosis of acute oxalate nephropathy (109962).
Other ...Intravenously, hypernatremia and falsely elevated ketone levels is reported in a patient with septic shock and chronic kidney disease after a high-dose vitamin C infusion. The hypernatremia resolved over 24 hours after cessation of the infusion (112479).
