Each tablet contains: Proprietary Blend 198 mg: Acerola berry, Rose Hips , Dried Buckwheat juice, Buckwheat seed • Vitamin C 5.4 mg • Echinacea root 135 mg. Other Ingredients: Honey, Calcium Stearate.
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 Echinacea C. 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
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Echinacea C. 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.
POSSIBLY SAFE ...when used orally and appropriately (11438,11442).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately, short-term. Various liquid extracts of Echinacea purpurea have been used safely for up to 10 days, including EchinaGuard (Madaus AG) 20 drops every 2 hours for 1 day, then three times daily (10320), or Echinilin (Inovobiologic Inc.) 40 mL in divided doses for 1 day, then 15 mL in divided doses daily thereafter (12355,20062). Other liquid extracts have been used safely for relatively longer periods, including Echinaforce (A. Vogel Bioforce AG) 2.4 grams daily for 4 months or 1.6 grams daily for 6 months (7087,18225), and Echinacin (Madaus AG) 5 mL twice daily for 10 days, or 4 mL twice daily for 8 weeks (3282,10802). Specific solid dosage forms of echinacea that have been used safely for up to 10 days include Echinacea purpurea above-ground parts (EchinaFresh, Enzymatic Therapy) 300 mg daily (11970), and mixtures of Echinacea purpurea and Echinacea angustifolia herb in divided doses of 6 grams to 10.5 grams for 1 day then 3 grams to 5.1 grams daily (10800,17519,20059). A specific Echinacea angustifolia extract (ExtractumPharma ZRT) has also been used with apparent safety at a dose of 40 mg once or twice daily for up to 7 days (20064,103233). An Echinacea purpurea product (Natures Resource) has been used safely at a dose of 1.8 grams daily for 8 weeks (17521), and echinacea (Puritan's Pride) has been used safely at 8 grams daily for 28 days (20066).
POSSIBLY SAFE ...when used topically, short-term. A specific cream (Linola Plus Cream, Dr. August Wolff GmbH & Co.) containing echinacea extract (WO 3260) has been applied to the skin safely 2-3 times daily for up to 12 weeks (97499). There is insufficient reliable evidence about the safety of echinacea when used parenterally.
CHILDREN: POSSIBLY SAFE
when used orally, short-term.
Some clinical research shows that an extract of the above-ground parts of Echinacea purpurea (EC31J2, Echinacin Saft, Madaus AG) in a dose of 3.75 mL twice daily (for ages 2 years to 5 years) or 7.5 mL twice daily (for ages 6 years to 11 years) is safe when used for up to 10 days (4989). However, about 7% of children experienced a rash after taking echinacea, which might have been caused by an allergic reaction (4989). There is concern that allergic reactions could be severe in some children. The Medicines and Healthcare Products Regulatory Agency in the United Kingdom recommends against the use of oral echinacea products in children under 12 years of age due to this risk of allergic reaction (18207). In contrast, another clinical study in children 4-12 years old shows that a specific Echinacea purpurea product (Echinaforce Junior, A. Vogel) does not cause allergic or urticarial reactions more frequently than vitamin C (105719).
PREGNANCY: POSSIBLY SAFE
when used orally, short-term.
There is preliminary evidence that mothers can safely use echinacea in the form of E. purpurea or E. angustifolia solid dosage forms, 250-1000 mg daily, or tinctures, up to 30 drops daily, for 5 days to 7 days during the first trimester without adversely affecting the fetus (7056,13418,15123). There is insufficient reliable information available about the safety of echinacea when used for longer than 7 days.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when rose hip extract is used orally in the amounts found in foods. Rose hip extract has Generally Recognized as Safe (GRAS) status in the US (4912). ...when rose hip from Rosa canina is used orally and appropriately in medicinal amounts. A specific formulation of rose hip powder from Rosa canina (LitoZin/i-flex, Hyben Vital), taken in doses of up to 2.5 grams (5 capsules) twice daily, has been safely used for up to 6 months (17416,71641,71646,71658,71660,71661,104557). Rose hip powder from Rosa canina, 40 grams daily mixed in apple juice, has been used safely for up to 6 weeks (18104). Rose hip powder from Rosa canina, 500 mg twice daily for 20 days, has also been safely used (97938).
POSSIBLY SAFE ...when rose hip from Rosa damascena is used orally and appropriately in medicinal amounts. Rose hip extract from Rosa damascena has been used safely in doses of 200 mg every 6 hours for 3 days (104555). There is insufficient reliable information available about the safety of medicinal amounts of rose hip from other Rosa species. There is also insufficient reliable information available about the safety of rose hip when used topically.
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of rose hip when used orally or topically in medicinal amounts; avoid using in amounts greater than those found in foods.
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).
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 Echinacea C. 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.
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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.
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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.
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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.
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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).
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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.
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Echinacea can increase plasma levels of caffeine by inhibiting its metabolism.
Details
Echinacea seems to increase plasma concentrations of caffeine by around 30% (12155). This is likely due to inhibition of cytochrome P450 1A2 (CYP1A2) by echinacea.
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Echinacea might inhibit the metabolism of CYP1A2 and increase plasma levels of some drugs.
Details
Echinacea appears to inhibit CYP1A2 enzymes in humans. Additionally, echinacea seems to increase plasma concentrations of caffeine, a CYP1A2 substrate, by around 30% (12155). Theoretically, echinacea might increase levels of other drugs metabolized by CYP1A2.
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Echinacea may induce hepatic CYP3A4 and inhibit intestinal CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Details
Several clinical trials have shown that taking echinacea for up to one month does not significantly affect the metabolism of various CYP3A4 substrates, including midazolam, docetaxel, etravirine, lopinavir-ritonavir, and darunavir-ritonavir (13712,48618,88164,88165). However, other clinical research shows that echinacea may increase the clearance of midazolam, suggesting that echinacea might induce CYP3A4 (48618). The discrepancy is thought to be due to differing effects of echinacea on intestinal versus hepatic CYP3A4 enzymes. Echinacea appears to induce hepatic CYP3A4 but inhibit intestinal CYP3A4 (12155). In some cases, these effects might cancel each other out, but in others, drug levels may be increased or decreased depending on the level of effect at hepatic and intestinal sites. The effect of echinacea on CYP3A4 activity may differ depending on the CYP3A4 substrate (6450,11026,88162,88167).
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Theoretically, echinacea may interfere with the metabolism of darunavir; however, a small clinical study found no effect.
Details
Darunavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but administration of an E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg four times daily for 14 days did not affect darunavir/ritonavir pharmacokinetics in 15 HIV-infected patients (88163,93578).
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Theoretically, echinacea may interfere with the metabolism of docetaxel; however, a small clinical study found no effect.
Details
Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea whole plant extract (Echinaforce, A. Vogel Biopharma AG) 20 drops three times daily for 2 weeks did not alter the pharmacokinetics of docetaxel in one clinical study (88164).
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Echinacea may increase levels of etoposide.
Details
In one report, concomitant use of etoposide and echinacea was associated with more severe thrombocytopenia than the use of etoposide alone, suggesting inhibition of etoposide metabolism (20082). Etoposide is a cytochrome P450 3A4 (CYP3A4) substrate. Echinacea has variable effects on CYP3A4, but some studies have reported inhibition of the enzyme (6450,11026,12155,88162,88167).
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Theoretically, echinacea may interfere with the metabolism of etravirine; however, a small clinical study found no effect.
Details
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Echinacea has immunostimulant activity which may interfere with immunosuppressant therapy.
Details
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Theoretically, echinacea may interfere with the metabolism of lopinavir; however, a small clinical study found no effect.
Details
Lopinavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but taking E. purpurea (Echinamide, Natural Factors Nutritional Products, Inc.) 500 mg three times daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in healthy volunteers (48618,93578).
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Theoretically, echinacea may increase the metabolism of intravenous midazolam.
Details
Echinacea induces hepatic CYP3A4 and might decrease plasma levels of midazolam by about 20%, reducing the effectiveness of intravenous midazolam (12155). Echinacea also appears to inhibit intestinal CYP3A4, which could theoretically increase the bioavailability of oral midazolam. This may cancel out the decrease in availability caused by induction of hepatic CYP3A4, such that overall plasma levels after oral administration of midazolam are not affected by echinacea.
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Echinacea seems to increase the clearance of warfarin, although the effect may not be clinically significant.
Details
Preliminary clinical research in healthy male volunteers suggests that taking echinacea increases the clearance of the active S-isomer of warfarin after a single dose of warfarin, but there was not a clinically significant effect on the INR (20083).
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Theoretically, the antioxidant effects of rose hip might reduce the effectiveness of alkylating agents but might also reduce the oxidative damage caused by certain alkylating agents.
Details
Rose hip contains vitamin C. 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). Further, some animal research suggests that the antioxidant effects of rose hip might attenuate cyclophosphamide-induced testicular toxicity (111413). More evidence is needed to determine what effect, if any, antioxidants found in rose hip, such as vitamin C, have on the effectiveness and adverse effects of chemotherapy.
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Theoretically, rose hip might increase the amount of aluminum absorbed from aluminum compounds.
Details
Rose hip contains vitamin C. Theoretically, vitamin C increases the absorption of aluminum. Concomitant use might increase aluminum absorption, but the clinical significance of this is unknown (3046). Administer rose hip two hours before or four hours after antacids.
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Theoretically, rose hip might reduce the effectiveness of anticoagulant or antiplatelet drugs.
Details
In vitro and animal research suggests that a constituent of rose hip, rugosin E, can induce platelet aggregation (71653). This has not been shown in humans. Theoretically, concomitant use of rose hip might reduce the effectiveness of antiplatelet or anticoagulant drugs.
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Theoretically, the antioxidant effects of rose hip might reduce the effectiveness of antitumor antibiotics.
Details
Rose hip contains the antioxidant vitamin C. 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.
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Theoretically, rose hip might reduce the clearance of aspirin; however, its vitamin C content is likely too low to produce clinically significant effects.
Details
Rose hip 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 rose hip is typically about 500 mg per 100 grams. Thus, a clinically significant interaction between rose hip and aspirin is unlikely.
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Theoretically, rose hip might increase blood levels of estrogens.
Details
Rose hip contains vitamin C. Increases in plasma estrogen levels of up to 55% have occured 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).
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Theoretically, rose hip might increase blood levels of lithium.
Details
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Theoretically, rose hip might reduce the effectiveness of warfarin; however, its vitamin C content is likely too low to produce clinically significant effects.
Details
Rose hip 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 rose hip is typically about 500 mg per 100 grams. Thus, a clinically significant interaction between rose hip and warfarin is unlikely.
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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 Echinacea C. 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, buckwheat seems to be well tolerated (11438,11442). However, allergic reactions to buckwheat can occur in some adults and children. Symptoms can include skin sensitization, allergic rhinitis, asthma, conjunctivitis, nausea, vomiting, and anaphylaxis (11435,11436,11437,96060,96061). Occupational exposure to buckwheat, or household exposure through sleeping on a buckwheat husk stuffed-pillow can cause sensitization, of which symptoms include allergic rhinitis and asthma (11437,11443).
Immunologic
...Orally, buckwheat seems to be well tolerated (11438,11442).
However, allergic reactions to buckwheat can occur in some adults and children. Symptoms can include skin sensitization, allergic rhinitis, asthma, conjunctivitis, nausea, vomiting, and anaphylaxis (11435,11436,11437,96060,96061).
Occupational exposure to buckwheat, or household exposure through sleeping on a buckwheat husk stuffed-pillow can cause sensitization, of which symptoms include allergic rhinitis and asthma (11437,11443).
General
...Orally, echinacea is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, heartburn, nausea and vomiting, rashes, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions and hepatitis have been reported.
Dermatologic ...Itching, urticaria, tingling, and allergic rashes have been reported with various echinacea preparations (8225,12355,17519,20059,20077,101592,111530,111540). In a study of children aged 2-11 years, rash occurred in about 7% of children treated with an extract of the above-ground parts of E. purpurea (EC31J2, Echinacin Saft, Madaus AG), compared with about 3% of those treated with placebo (4989,95652). There is concern that allergic reactions could be severe in some children. The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) recommends against the use of oral echinacea products in children under 12 years of age due to this risk of allergic reaction (18207). However, another study in children 4-12 years old shows that a specific E. purpurea product (Echinaforce Junior, A. Vogel) did not cause allergic or urticarial reactions more frequently than vitamin C (105719).
Gastrointestinal ...Gastrointestinal adverse effects include nausea and vomiting, abdominal pain, stomach upset, heartburn, diarrhea, and constipation (10802,11970,12355,13419,17519,20059,48680,105719,106626). An unpleasant taste, dry mouth, and burning, tingling or numbness of the tongue also occur (11970,12355,17519,20059,20070,20077).
Hematologic ...A 51-year-old female presented with leukopenia after taking echinacea 450 mg three times daily for 2 months, along with ginkgo biloba, multivitamins, and calcium. Her leukocyte count recovered upon stopping these supplements, but dropped again when she restarted echinacea alone about a year later. The problem resolved when echinacea was stopped permanently (48533). A 32-year-old male presented with severe thrombotic thrombocytopenic purpura (TTP) about 2 weeks after using an extract of E. pallida to treat a cold. He required admission to an intensive care unit and extensive plasmapheresis. The authors speculate that immunostimulant effects of echinacea induced or exacerbated the TTP (48572).
Hepatic
...Although uncommon, cases of echinacea-induced hepatitis have been reported.
One case report describes acute cholestatic autoimmune hepatitis in a 45-year-old male who had been taking an echinacea root extract 1500 mg daily for about 2 weeks. He presented with significantly elevated liver function tests (LFTs), elevated immunoglobulin G (IgG) levels, and a positive test for anti-smooth muscle antibodies, indicating an autoimmune process. Elevated LFTs and IgG levels returned to normal within one month of stopping echinacea (17518). Another case report describes acute cholestatic hepatitis in a 44-year-old male who had taken echinacea root tablets 600 mg daily for 5 days to treat flu-like symptoms. He presented with elevated LFTs, prothrombin time, and international normalized ratio (INR). His condition gradually improved after stopping echinacea, and his LFTs normalized within 3 months (91528).
Seven cases of hepatitis associated with echinacea use were reported to the Australian Adverse Drug Reactions Advisory Committee between 1979 and 2000, but specific details are lacking (8225).
One case report describes acute liver failure in a 2 year-old child who had been given about 100 mg of echinacea daily for 2 weeks. The patient presented with jaundice, diarrhea, lethargy, anorexia, and significantly elevated LFTs. A liver biopsy showed hepatocyte swelling, spotty necrosis, and inflammatory infiltrate with eosinophils. A full recovery was made over a 2-week period (88166).
Immunologic
...Allergic reactions, including urticaria, runny nose, dyspnea, bronchospasm, acute asthma, angioedema, and anaphylaxis, have been reported with various echinacea preparations (638,1358,8225).
Atopic individuals and those sensitive to other members of the Asteraceae family (ragweed, chrysanthemums, marigolds, daisies) seem to be at higher risk for these reactions (1358,8225).
A case report describes a 36-year-old female who presented with muscle weakness, electrolyte abnormalities, renal tubular acidosis, fatigue, and dry mouth and eyes after taking echinacea, kava, and St. John's Wort for 2 weeks., She also had a positive antinuclear antibody (ANA) test, with elevated anti-dsDNA antibodies SSA and SSB. Sjogren syndrome was diagnosed; the authors hypothesize that it may have been triggered by the immunostimulant effects of echinacea (10319). A 55-year-old male with a history of pemphigus vulgaris in remission for about a year experienced a flare of the disease after taking an echinacea supplement for one week. After stopping echinacea, medical treatment resulted in partial control of the disease (12171). Another case report describes a 58-year-old male who presented with marked eosinophilia and elevated immunoglobulin E (IgE) levels while taking an echinacea supplement. He required prednisone therapy until he stopped taking echinacea 3 years later, at which time his eosinophils and IgE normalized (48623). A 41-year-old male experienced four episodes of erythema nodosum, each occurring after he had taken echinacea for early symptoms of influenza. After stopping echinacea, he had no further exacerbations of erythema nodosum, suggesting that it had been triggered by the immunostimulant effects of echinacea (7057).
Musculoskeletal ...Reports of arthralgia and myalgia have been associated with echinacea (13418).
Neurologic/CNS ...Headache has been reported in people taking various echinacea preparations orally (3282,11970,17519,20059,20064). Dizziness has also been reported (3282,8225,11970). In one study using an alcoholic extract of the above-ground parts of E. purpurea (EC31J0, Echinacin, Madaus AG), somnolence and a tendency to aggressiveness were reported (3282).
General
...Orally, rose hip from Rosa canina is well tolerated.
Rose hip from Rosa damascena also seems to be well tolerated. A thorough evaluation of safety outcomes has not been conducted for rose hip derived from other species.
Most Common Adverse Effects:
Orally: Flatulence, loose stools.
Dermatologic ...Orally, one case of mild urticaria has been reported in a clinical trial for a patient taking a specific rose hip powder product (LitoZin/i-flex, Hyben Vital) 2. 5 grams twice daily (71646).
Gastrointestinal
...Orally, gastrointestinal reactions have been reported.
These include abdominal cramps, acid reflux, constipation, diarrhea, flatulence, nausea, vomiting, gastrointestinal obstruction, esophagitis, heartburn, acid reflux, and water brash. However, in most cases, these adverse effects occurred at the same frequency in patients taking placebo (15,18104,71641,71646,97938).
Rose hip powder is a source of vitamin C. 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). However, most rose hip products contain only 500 mg of vitamin C per 100 grams.
Genitourinary ...Orally, a few mild cases of frequent voiding have been reported in clinical trials. However, the frequency of occurrence does not seem to differ from those taking placebo (71641,71646).
Immunologic ...When inhaled in the workplace, rose hip dust has caused mild to moderate anaphylaxis (6).
Neurologic/CNS ...Orally, vertigo and headache have been reported rarely (97938).
Ocular/Otic ...A case of keratoconjunctivitis secondary to contact with rose hip has been reported. The adverse effect was attributed to irritant hairs found on the fruit of rose hip. Symptoms resolved after treatment with topical prednisolone 1% eye drops (71642).
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).
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). 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).
