| Ingredients | Amount Per Serving |
|---|---|
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(Ascorbic Acid)
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250 mg |
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3 in 1 Creatine Complex
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6.25 Gram(s) |
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(NO3-T)
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Natural & Artificial flavors, Citric Acid, Silicon Dioxide (Alt. Name: SiO2), Sucralose, Acesulfame Potassium, FD&C Red # 40
Below is general information about the effectiveness of the known ingredients contained in the product CN3 Fruit Punch. 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
Below is general information about the safety of the known ingredients contained in the product CN3 Fruit Punch. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally and appropriately, short-term. Creatine supplementation appears to be safe when used at loading doses of up to 25 grams daily or 0.3 grams/kg daily for up to 14 days in healthy adults (1367,2100,2101,3996,4569,10064,15354,15520,46570,46587)(46673,46688,46719,46753,46801,103278,103279,108336). Creatine supplementation also appears to be safe when used at maintenance doses of 4-5 grams daily for up to 18 months (2101,4578,15353,15354,15520,46587,46673,46690,46753,46838,102164,103278,108336).
POSSIBLY SAFE ...when used orally and appropriately, long-term. Creatine supplementation has been safely used at doses of up to 10 grams daily for up to 5 years in some preliminary clinical research (1367,3996). There is insufficient reliable information available about the safety of creatine when used topically.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Creatine supplementation appears to be safe when used in appropriate doses in infants and children. Creatine 3-5 grams daily for 2-6 months has been safely used in children 5-18 years of age (6182,46596,46739,46841). Creatine 2 grams daily for 6 months has been safely used in children 2-5 years of age (46841). Additionally, weight-based dosing of creatine 0.1-0.4 grams/kg daily in infants and children or 4.69 grams/m2 in children weighing over 40 kg has been used safely for up to 6 months (46623,46629,46694,46759,104672).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
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 CN3 Fruit Punch. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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).
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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).
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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.
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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.
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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.
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Below is general information about the adverse effects of the known ingredients contained in the product CN3 Fruit Punch. 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, creatine is generally well-tolerated.
Topically, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Dehydration, diarrhea, gastrointestinal upset, muscle cramps, and water retention.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about interstitial nephritis, renal insufficiency, rhabdomyolysis, and venous thrombosis.
Cardiovascular
...Some research suggests that creatine supplementation can cause edema.
In a randomized controlled trial, 26% of patients with amyotrophic lateral sclerosis (ALS) receiving creatine 10 grams daily reported edema after 2 months of treatment compared to 9% with placebo. The difference between groups was statistically significant at 2 months but not at month 4 and beyond. Creatine is believed to cause slight water retention, which may have been more apparent in patients who were immobilized due to ALS (46647). While this adverse drug reaction did not lead to worsening cardiac function in these patients, theoretically, creatine-related water retention could worsen congestive heart failure or hypertension.
There is one case report of lone atrial fibrillation in a 30-year-old male vegetarian. He started powdered creatine 20 grams daily for 5 days, followed by 2.5 grams daily for a month. However, he discontinued powdered creatine due to severe cramping and diarrhea, and reinitiated creatine supplementation a month later with an encapsulated formulation. Aside from gelatin in the capsule, creatine was the only ingredient listed in both formulations. During the loading dose phase, the patient developed dyspnea and palpitations and was diagnosed with lone atrial fibrillation in the emergency department. Symptoms resolved with treatment and supplement discontinuation (13187). Theoretically, alterations in electrolyte balance due to dehydration or diarrhea could lead to conduction abnormalities and arrhythmia; however, in this case, the patient had normal electrolyte levels. Contaminants in dietary supplements might also be responsible for adverse reactions; this specific creatine product was not tested for contaminants. It remains unclear whether creatine was associated with this event.
Theoretically, taking creatine nitrate might reduce blood pressure and heart rate due to its nitrate component. However, clinical research shows that creatine nitrate 12 grams daily for 7 days followed by 3 grams daily for 21 days does not lower blood pressure or heart rate acutely or chronically when compared to creatine monohydrate or placebo (95959).
Dermatologic
...In a small clinical trial of older, healthy males, one subject out of the 10 receiving creatine 5 grams four times daily for 10 days followed by 4 grams daily for 20 days reported a skin rash during the study.
The type and severity of rash and whether it resolved after creatine was discontinued were not discussed (4572). Also, skin rash has been reported by patients taking celecoxib and creatine; however, whether this effect was due to creatine or celecoxib is unclear (46706).
Topically, burning, itching, redness, irritation, and perception of changes in skin temperature have been reported (104669).
Endocrine ...Creatine may influence insulin production (11330). In human research, insulin levels increased 120 and 240 minutes after creatine supplementation (46760); however, there was no effect in another trial (46732). In a clinical study, 0.3 grams/kg of creatine daily for one week significantly increased cortisol levels by 29%. However, the levels returned to baseline at week 2 (46615).
Gastrointestinal
...Some small clinical studies have reported diarrhea and vomiting with oral creatine supplementation (4584,11332,46562,46684,46698,46704,104673).
Also, gastrointestinal distress, transient abdominal discomfort, constipation, heartburn, and nausea have been reported by a small number of individuals in randomized, controlled clinical trials (4572,11332,46527,46528,46573,46589,46622,46668,46684,46695), (46704,46771,95964,104668,104669,104673,108316). However, most high-quality clinical research shows that creatine does not increase the incidence of gastrointestinal upset (103102,103278,103279).
Undissolved creatine powder may cause gastroenteritis (1368). Additionally, simultaneous intake of creatine and caffeine powder may increase the occurrence of gastrointestinal distress (95964).
Hematologic ...There are two case reports of creatine-related venous thrombosis in otherwise healthy adults. In the first case, an active 18-year-old male who had been taking an unspecified dose of creatine daily for 3 months was diagnosed with venous thrombosis via MRI. The patient reported increased thirst and fluid consumption when taking creatine. In the second case, an active 31-year-old male who had recently taken a 5-hour flight was diagnosed with deep vein thrombosis. He had been taking an unspecified dose of creatine. After stopping creatine and receiving anticoagulation therapy for 6 months, both patients' thromboses were resolved and did not recur. Researchers speculate that dehydration might be to blame for these adverse events, as dehydration increases the risk of thrombosis. In both cases, thrombophilic conditions were ruled out, and a temporal relationship between creatine consumption and thrombosis was established (90301). However, it remains unclear if creatine was responsible for these thrombotic events.
Hepatic
...Despite two case reports describing hepatic injury in patients taking creatine (46701,90319), meta-analyses and clinical studies specifically evaluating the safety of creatine have not identified an increased risk for hepatic injury (103278,103279).
In addition, population research suggests that there is not an association between creatine intake and liver fibrosis, cirrhosis, or hepatic steatosis. However, this study largely included subjects consuming less than 4 grams daily (112208).
One preliminary clinical trial specifically evaluated the effect of creatine loading and maintenance doses on hepatic function indices in healthy adults. No clinically significant changes in hepatic indices were reported in patients taking creatine loading doses of 20 grams daily for 5 days followed by maintenance doses of 3 grams daily for 8 weeks (46521). Another clinical study evaluated the impact of creatine monohydrate and creatine nitrate on liver function enzymes, showing no change in levels within 5 hours after the first dose of 12 grams or after continued consumption of 12 grams daily for 7 days followed by 3 grams daily for 21 days (95959). The patients that experienced hepatic injury in the available case reports were also taking other exercise supplements. Whether the reported adverse hepatic effects were due to creatine or the other supplements patients were taking is unclear. Also, neither of these case reports addressed whether the supplements were tested for contamination (46701,90319).
Musculoskeletal ...Creatine-associated increase in body mass is well documented in randomized, controlled clinical trials and is often as large as 1-2 kg during the five-day loading period of creatine (2101,4569,4589,4591,4600,4605,46504,46561,46815,46827)(46830,46843,95962,103279,112201). This may be considered an unwanted adverse reaction in some individuals and a desired effect of supplementation in others. This weight gain may interfere with mass-dependent activities such as running and swimming (46504,46823). Muscle cramping due to creatine supplementation has been reported in controlled clinical trials and may result from water retention in skeletal muscle (2104,4572,4584,30915,46562,46695,46826,46827,104673). However, most high quality clinical research shows that creatine does not increase the incidence of musculoskeletal injuries or muscle cramping (103102). In one case report, rhabdomyolysis in a weight lifter using creatine 25 grams daily over a one-year period has been reported (12820). Another case report describes an adult male who developed acute compartment syndrome of the leg after regular consumption of an unspecified amount of creatine and cocaine (112210).
Neurologic/CNS ...In clinical research, thirst, sleepiness, mild headache, and syncope have been reported for patients taking creatine, although the events were uncommon (46578,46615,46820). More serious adverse events have been reported for patients taking creatine in combination with other ingredients. A case of ischemic stroke has been reported for an athlete who consumed creatine monohydrate 6 grams, caffeine 400-600 mg, ephedra 40-60 mg, and a variety of other supplements daily for 6 weeks (1275). In another case, a 26 year old male reported with a hemorrhagic stroke linked to taking the supplement Jack3d, which contains creatine, DMAA, schizandrol A, caffeine, beta-alanine, and L-arginine alpha-ketoglutarate (90318). It is likely that these adverse events were due to other ingredients, such as caffeine, ephedra, and DMAA, which are known to have stimulant and vasoconstrictive properties.
Oncologic ...Population research shows that use of muscle building supplements such as creatine, protein, and androstenedione is associated with an increased odds of testicular germ cell cancer. This risk appears to be more apparent in early users, those using two or more muscle building supplements, and those with long-term use of the supplements. The odds of testicular germ cell cancer may be increased by up to 155% in males taking both creatine and protein supplements (90329). The risk of testicular germ cell cancer from creatine alone is unclear from this study.
Psychiatric ...Anxiety, irritability, depression, aggression, and nervousness have been reported in clinical research for patients taking creatine, although the effects are not common (46518). A case of acute organic psychosis was reported in a 32-year-old soldier in Iraq who was consuming excessive amounts of caffeine coupled with use of creatine (Creatamax, MaxiNutrition) one tablet twice daily for 3 weeks plus a specific stimulant containing bitter orange, guarana seed extract, and St. John's wort extract (Ripped Fuel Ephedra Free, Twinlabs) two tablets three times daily for 2 days prior to admission. The psychosis was considered likely due to caffeine consumption in combination with the stimulant supplement rather than creatine (37982).
Renal
...Isolated cases of renal dysfunction in patients taking creatine have been reported, including a case of interstitial nephritis in a healthy male (184) and a case of renal insufficiency in a football player (46828).
In contrast to these cases, several clinical studies and case reports have shown that creatine does not affect markers of renal function in healthy adults (2120,3996,4573,16535,46735,46749,46758,46779,46813,95959,103279). Doses studied included 5- to 7-day loading regimens of 12 to 21 grams daily (2120,46813), or maintenance doses of 3-10 grams daily for up to 2 years (16535,46712,46758,95959). In two additional studies, creatine supplementation 15.75 grams for 5 days followed by 4.25 grams daily for 20 days with carbohydrate and protein ingestion led to no change of renal stress markers (46844). Other clinical research has shown that ingestion of creatine up to 30 grams daily for 5 years is not associated with an increased incidence of renal dysfunction (103102).
Other case reports involve patients with pre-existing renal dysfunction. For example, in one case, a patient with a history of recurrent renal failure developed relapsing steroid-responsive nephritis syndrome after taking creatine (1368,2118). In another case, a patient with diabetic nephropathy who was taking creatine and metformin developed severe metabolic acidosis and acute renal failure. It is unclear if creatine contributed to this event, as metformin alone is known to cause metabolic acidosis (46738). These case reports have raised concern that individuals with pre-existing renal dysfunction may be at increased risk for renal injury with creatine supplementation. However, no prospective clinical trials have been conducted in this population to clarify this concern.
In addition, two cases of acute kidney injury and hypercalcemia have been reported in 16 year old males that took 1-4 servings of creatine for less than 4 weeks; however, the creatine product contained unlabeled, very high doses of vitamin D, which is the likely cause of these symptoms (109739).
In one survey, 13% of male collegiate athletes taking creatine reported dehydration (4584). The Association of Professional Team Physicians has warned that creatine may cause dehydration, heat-related illnesses, and electrolyte imbalances, and reduce blood volume. Mild transient dehydration resulting in an elevated serum creatinine was also reported in a single person in a clinical trial (104672). However, a study found that creatine supplementation during preseason football training had no effect on fluid or electrolyte status (46845). Additionally, most high quality clinical research shows that creatine does not increase dehydration (103102). A theoretical increase in risk of dehydration due to intracellular fluid shifts has led most creatine manufacturers to caution about adequate hydration with creatine supplementation (4576).
Other
...There have been reports of heat intolerance with oral creatine supplementation (46505).
Increases in formaldehyde production have been reported with creatine use. A-24 year-old man taking supratherapeutic doses of creatine monophosphate in combination with an energy supplement developed malignant hyperthermia after undergoing anesthesia. His symptoms included tachycardia, hypertension, hypercarbia, and hyperthermia. Environmental factors are suspected to have played a role in the development of malignant hyperthermia, so whether this adverse event was due to creatine at all is unclear (46717).
In 1997, three collegiate wrestlers died after engaging in a rapid weight-loss program in order to qualify for competition (93628). Initially creatine supplementation was considered to have contributed to or caused these deaths (12820,93629); however, investigations by the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) did not confirm this belief (12820,93630). It appears that only one of the three wrestlers had been using creatine. Instead, the deaths were related to drastic, short-term weight loss in which the wrestlers wore rubber suits, avoided hydration, and performed workouts in rooms with temperatures up to 33 °C (1368,93631).
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).
