Ingredients | Amount Per Serving |
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800 mcg | |
(root)
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800 mg |
Cellulose, Microcrystalline Cellulose, Magnesium Stearate (Alt. Name: Mg Stearate), Silicon Dioxide (Alt. Name: SiO2)
Below is general information about the effectiveness of the known ingredients contained in the product Cassanovum Original. 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 Cassanovum Original. 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 in food amounts that have been processed appropriately to remove cyanogenic glycosides. Cassava flour that contains no more than 10 ppm of cyanide is considered safe by the World Health Organization (25869,26585). Grating and crushing are considered to be appropriate processing methods to remove cyanide from bitter or sweet cassava root. Sweet cassava may be processed by boiling, steaming, baking, or frying (25841,26585). Boiling, steaming, baking, or frying are not considered to be sufficient processing methods to remove cyanide from bitter cassava (26585).
POSSIBLY UNSAFE ...when used orally in food amounts that have not been processed appropriately to remove cyanogenic glycosides. Regularly consuming uncooked cassava or cassava that has not been processed appropriately, especially as part of a protein-deficient diet, increases exposure to cyanogenic glycosides (25844). Heap fermentation or sun drying are not considered to be appropriate processing methods for removing cyanide from bitter or sweet cassava root (26585). Boiling, steaming, baking, or frying are not considered to be appropriate processing methods for removing cyanide from bitter cassava (26585). There is insufficient reliable information available about the safety of using cassava in medicinal amounts.
CHILDREN: POSSIBLY SAFE
when used orally in food amounts.
Cassava is commonly consumed as a food with apparent safety. However, regular cassava consumption by children has been associated with inadequate intake of vitamin A, zinc, and iron (26175). Also, cassava may contain cyanogenic glycosides, and children are at a higher risk of cyanide poisoning from cassava compared to adults (25843).
CHILDREN: POSSIBLY UNSAFE
when used orally as a food in large quantities.
Epidemiological research has found that children who eat more than 700 grams of cassava daily may have a higher risk of developing konzo, a paralytic disease, than those who eat less than 150 grams daily (25860).
PREGNANCY: POSSIBLY UNSAFE
when used orally as a food, especially in large quantities.
Animal research suggests that consuming milled cassava powder as 80% of the diet during the first 15 days of pregnancy can cause teratogenic effects, including intrauterine growth restriction, limb defects, and abnormally small brain (microencephaly) (26171). Also, epidemiological evidence suggests that pregnant women who regularly consume dietary cassava in the form of gari during pregnancy have higher levels of thiocyanate, which has negative effects on fetal birthweight, compared to those who do not consume cassava (26172). ...when applied intravaginally. Inserting 2-3 cm of cassava stalk into the vagina has been used to induce abortion and labor (26174).
LACTATION: POSSIBLY UNSAFE
when used orally in food amounts, especially in large quantities.
Excess consumption of cassava during lactation may increase the risk of exposing the infant to thiocyanate, which can negatively affect thyroid function in the infant (26586).
LIKELY SAFE ...when used orally or parenterally and appropriately. Folic acid has been safely used in amounts below the tolerable upper intake level (UL). The UL for folic acid is based only on supplemental folic acid and is expressed in mcg folic acid. Dietary folate is not included in UL calculations, as dietary folate consumption has not been associated with adverse effects. The UL for folic acid in adults is 1000 mcg (6241). In cases of megaloblastic anemia resulting from folate deficiency or malabsorption disorders such as sprue, oral doses of 1-5 mg per day can also be used safely until hematologic recovery is documented, as long as vitamin B12 levels are routinely measured (6241,7725,8739).
POSSIBLY SAFE ...when L-5-methyltetrahydrofolate (L-5-MTHF), the reduced form of folate, is used orally and appropriately, short-term. L-5-MTHF has been used with apparent safety at a dose of 416 mcg daily for 16 weeks (104913,104914) and a dose of 113 mcg daily for 24 weeks (104920). A specific L-5-MTHF product (Metafolin, Eprova) has been used with apparent safety at a dose of 1.3 mg daily for 12 weeks (104912).
POSSIBLY UNSAFE ...when used orally in large doses, long-term. Clinical research shows that taking folic acid daily in doses of 800 mcg to 1200 mcg for 3-10 years significantly increases the risk of developing cancer and adverse cardiovascular effects compared to placebo (12150,13482,16822,17041). Doses above 1 mg per day should also be avoided if possible to prevent precipitation or exacerbation of neuropathy related to vitamin B12 deficiency (6241,6242,6245). However, there is contradictory evidence suggesting that higher doses may not be harmful. There is some evidence that doses of 5 mg per day orally for up to 4 months can be used safely if vitamin B12 levels are routinely measured (7725). Also, other clinical research suggests that folic acid supplementation at doses up to 5 mg, usually in combination with vitamin B12, does not increase the risk of cancer when taken for 2-7 years (91312). Very high doses of 15 mg per day can cause significant central nervous system (CNS) and gastrointestinal side effects (505).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Folic acid has been safely used in children in amounts below the tolerable upper intake level (UL). The ULs for folic acid are based only on supplemental folic acid and are expressed in mcg folic acid. Dietary folate is not included in UL calculations, as dietary folate consumption has not been associated with adverse effects. The UL for children is: 1-3 years of age, 300 mcg; 4-8 years of age, 400 mcg; 9-13 years of age, 600 mcg; 14-18 years of age, 800 mcg (6241).
CHILDREN: POSSIBLY SAFE
when L-5-methyltetrahydrofolate (L-5-MTHF), the reduced form of folate, is used orally and appropriately.
One clinical study in infants aged 27 days and younger shows that consuming a formula containing L-5-MTHF (Metafolin, Merck & Cie) 10.4 mcg/100 mL daily has been used with apparent safety for up to 12 weeks (104918).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Folic acid 300-400 mcg is commonly used during pregnancy for prevention of neural tube defects (8739). Miscarriage rates and negative impacts on fetal growth have not been shown to increase with peri-conception supplemental folic acid intakes of 4 mg per day (91320,91322). However, other research shows that taking more than 5 mg per day during pregnancy may reduce development of cognitive, emotional, and motor skills in infants (91318). Also, the tolerable upper intake level (UL) of folic acid for pregnant or lactating women is 800 mcg daily for those 14-18 years of age and 1000 mcg daily for those 19 years and older (6241).
PREGNANCY AND LACTATION: POSSIBLY SAFE
when L-5-methyltetrahydrofolate (L-5-MTHF), the reduced form of folate, is used orally and appropriately, short-term.
L-5-MTHF has been used with apparent safety at a dose of 416 mcg daily for 16 weeks during lactation. Compared to folic acid, this form seems to further increase the folate concentration of red blood cells, but not breast milk (104913,104914).
Below is general information about the interactions of the known ingredients contained in the product Cassanovum Original. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Evidence from human and animal research suggests that cassava root has marked antithyroid effects, particularly if poorly processed or if consumed as part of a protein-deficient diet (25846,25848,25849,25850,25851,25852). Also, clinical research shows that consuming boiled cassava leaves 200 grams twice daily for 9 days significantly reduces levels of the thyroid hormones triiodothyronine and thyroxine (25847). Theoretically, cassava may alter thyroid function, reduce thyroid hormone levels, and interfere with thyroid hormone-replacement therapy.
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Theoretically, high doses of folic acid might increase the toxicity of 5-fluorouracil.
Details
Increases in gastrointestinal side effects of 5-fluorouracil, such as stomatitis and diarrhea, have been described in two clinical studies when leucovorin, a form of folic acid, was administered with 5-fluorouracil (16845).
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Use of high-dose folic acid might contribute to capecitabine toxicity.
Details
Clinical research suggests that higher serum folate levels are associated with an increased risk for moderate or severe toxicity during capecitabine-based treatment for colorectal cancer (105402). Additionally, in one case report, taking folic acid 15 mg daily might have contributed to increased toxicity, including severe diarrhea, vomiting, edema, hand-foot syndrome, and eventually death, in a patient prescribed capecitabine (16837).
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Folic acid might reduce the efficacy of methotrexate as a cancer treatment when given concurrently.
Details
Methotrexate exerts its cytotoxic effects by preventing conversion of folic acid to the active form needed by cells. There is some evidence that folic acid supplements reduce the efficacy of methotrexate in the treatment of acute lymphoblastic leukemia, and theoretically they could reduce its efficacy in the treatment of other cancers (9420). Advise cancer patients to consult their oncologist before using folic acid supplements. In patients treated with long-term, low-dose methotrexate for rheumatoid arthritis (RA) or psoriasis, folic acid supplements can reduce the incidence of side effects, without reducing efficacy (768,2162,4492,4493,4494,4546,9369).
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Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.
Details
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Folic acid might reduce serum levels of phenytoin in some patients.
Details
Folic acid may be a cofactor in phenytoin metabolism (4471). Folic acid, in doses of 1 mg daily or more, can reduce serum levels of phenytoin in some patients (4471,4477,4531,4536). Increases in seizure frequency have been reported. If folic acid supplements are added to established phenytoin therapy, monitor serum phenytoin levels closely. If phenytoin and folic acid are started at the same time and continued together, adverse changes in phenytoin pharmacokinetics are avoided (4471,4472,4473,4531). Note that phenytoin also reduces serum folate levels.
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Folic acid might have antagonistic effects on primidone and increase the risk for seizures.
Details
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Folic acid might antagonize the effects of pyrimethamine.
Details
Folic acid can antagonize the antiparasitic effects of pyrimethamine against toxoplasmosis and Pneumocystis carinii pneumonia. Folic acid doesn't antagonize the effects of pyrimethamine in the treatment of malaria, because malarial parasites cannot use exogenous folic acid. Use folinic acid as an alternative to folic acid when indicated (9380).
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Below is general information about the adverse effects of the known ingredients contained in the product Cassanovum Original. 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, cassava may cause cyanide poisoning. Cassava, especially the bitter variety, contains cyanogenic glycosides. If not removed during processing, these constituents are converted to cyanogens. Symptoms of cyanide poisoning can include vomiting, nausea, stomach pains, and diarrhea, as well as dizziness, weakness, and headache. (26585). Cassava intake has also been associated with an increased risk of hypothyroidism and endemic goiter. This adverse effect is attributed to cyanogens, which can disrupt thyroid hormone production by decreasing iodine absorption (25841,25843,25844). The risk of these adverse effects is especially high for patients who consume cassava as part of a protein-deficient diet (25841,25843,25844). Consumption of cassava that has not been processed to remove the cyanogens has also been associated with an increased risk of developing paralytic diseases, tropical pancreatitis, and tropical ataxic neuropathy (25844,25854,25856,25859,25860,25861,25863,25864). Rarely, cassava has been reported to cause allergic reaction (99802,99806,99807).
Endocrine
...Orally, cassava has been associated with an increased risk of hypothyroidism and endemic goiter, particularly when consumed after poor processing or along with a protein-deficient diet (25846,25850,25852).
Cassava, especially the bitter varieties, contains cyanogenic glycosides. If not removed during processing, these constituents are converted to cyanogens, which disrupt thyroid hormone production by decreasing iodine absorption (25841,25843,25844). In humans, consuming boiled cassava leaves 200 grams twice daily can decrease serum levels of the thyroid hormones triiodothyronine (T3) and thyroxine (T4) after only 9 days (25847).
There is also some concern that people who regularly consume cassava may have an increased risk of developing tropical pancreatitis, a form of pancreatitis that is primarily seen in tropical countries. However, this association has not been consistently observed (25854,25856).
Gastrointestinal ...Orally, cassava can cause cyanide poisoning. Cassava, especially the bitter varieties, contains cyanogenic glycosides. If not removed during processing, these constituents are converted to cyanogens. Gastrointestinal symptoms of cyanide poisoning can include vomiting, nausea, stomach pains, and diarrhea (26585).
Immunologic ...Rarely, cases of IgE-mediated allergic reaction have been reported after consumption of cassava. Reactions have included generalized urticaria, angioedema, respiratory distress, dry cough, and anaphylaxis. To date, all patients with confirmed cassava allergy also had an existing, confirmed latex allergy. It is hypothesized that cassava allergy results from primary sensitization to latex (99802,99806,99807).
Neurologic/CNS ...Orally, cassava can cause cyanide poisoning. Cassava, especially the bitter variety, contains cyanogenic glycosides. If not removed during processing, these constituents are converted to cyanogens. Neurological symptoms of cyanide poisoning include dizziness, weakness, and headache (26585). Evidence from case-control studies suggests that ingestion of wild or unprocessed cassava is associated with an increased risk of paralytic diseases, including spastic paraparesis, ataxic neuropathy, and konzo. People who consume wild or unprocessed cassava along with a protein-deficient diet seem to be at a particularly increased risk for these effects (25844,25859,25860,25861,99804). Although konzo is primarily a paralytic disease, children diagnosed with konzo have also demonstrated reduced mental and motor function (99805). Furthermore, children who have not been diagnosed with konzo but who live in a region where konzo is endemic demonstrate impairment in neurocognition and motor proficiency when compared with children in non-endemic regions. This suggests that there may be a subclinical form of the condition that causes neurocognitive complications (99805).
Ocular/Otic ...Orally, long-term consumption of wild or unprocessed cassava has been associated with the development of optic neuropathy and tropical ataxic neuropathy, presenting as loss of vision and hearing, particularly in protein-malnourished populations. Both of these conditions are attributed to cassava-induced cyanide overload (25863,25864,26585).
General
...Orally, folic acid is generally well-tolerated in amounts found in fortified foods, as well as in supplemental doses of less than 1 mg daily.
Most Common Adverse Effects:
Orally: At doses of 5 mg daily - abdominal cramps, diarrhea, and rash. At doses of 15 mg daily - bitter taste, confusion, hyperactivity, impaired judgment, irritability, nausea, sleep disturbances.
Serious Adverse Effects (Rare):
Orally: Cancer (long-term use), cardiovascular complications, liver injury, seizures.
All ROAs: Allergic reactions such as bronchospasm and anaphylactic shock.
Cardiovascular ...There is some concern that high oral doses of folic acid might increase the risk of adverse cardiovascular outcomes. Clinical research shows that taking doses of 800 mcg to 1.2 mg/day might increase the risk of adverse cardiovascular events in patients with cardiovascular disease (12150,13482). High doses of folic acid might promote cell growth by providing large amounts of the biochemical precursors needed for cell replication. Overgrowth of cells in the vascular wall might increase the risk of occlusion (12150). Although some research suggests that use of folic acid might increase the need for coronary revascularization, analysis of multiple studies suggests that taking folic acid up to 5 mg/day for up to 24 months does not appear to affect coronary revascularization risk (90798).
Dermatologic ...Orally, folic acid 1-5 mg daily can cause rash (7225,90375,91319). Folic acid 15 mg daily can sometimes cause allergic skin reactions (15).
Gastrointestinal ...Orally, folic acid 5 mg daily can cause abdominal cramps and diarrhea (7225). Folic acid 15 mg daily can sometimes cause nausea, abdominal distention, flatulence, and bitter taste in the mouth (15). In children aged 6-30 months at risk of malnourishment, taking a nutritional supplement (Nutriset Ltd) enriched in folic acid 75-150 mcg daily, with or without vitamin B 12 0.9-1.8 mcg daily, for 6 months increases the likelihood of having persistent diarrhea (90391).
Hepatic ...Liver dysfunction, with jaundice and very high liver enzymes, occurred in a 30-year-old pregnant patient with severe nausea and vomiting taking a folic acid supplement (Folic acid, Nature Made) 400 mcg daily. Based on the timing of ingestion, the lack of other etiological factors, a positive drug-induced lymphocyte stimulation test, and liver function normalization once the folic acid had been stopped, the authors suggest the folic acid supplement was the cause. However, the authors did not determine which substance in the folic acid supplement was responsible and therefore it cannot be determined that folic acid itself was the cause (91309).
Neurologic/CNS ...Orally, folic acid 15 mg daily can sometimes cause altered sleep patterns, vivid dreaming, irritability, excitability, hyperactivity, confusion, and impaired judgment (15). Large doses of folic acid can also precipitate or exacerbate neuropathy in people deficient in vitamin B12 (6243). Use of folic acid for undiagnosed anemia has masked the symptoms of pernicious anemia, resulting in lack of treatment and eventual neurological damage (15). Patients should be warned not to self-treat suspected anemia. There is also some concern that consuming high amounts of folic acid from the diet and/or supplements might worsen cognitive decline in older people. A large-scale study suggests that people over 65 years of age, who consume large amounts of folic acid (median of 742 mcg/day), have cognitive decline at a rate twice as fast as those consuming smaller amounts (median of 186 mcg/day). It's not known if this is directly attributable to folic acid. It is theorized that it could be due to folic acid masking a vitamin B12 deficiency. Vitamin B12 deficiency is associated with cognitive decline (13068). More evidence is needed to determine the significance of this finding. For now, suggest that most patients aim for the recommended folic acid intake of 400 mcg/day.
Oncologic
...There is some concern that high dose folic acid might increase the risk of cancer, although research is unclear and conflicting.
A large-scale population study suggests that taking a multivitamin more than 7 times per week with a separate folic acid supplement significantly increased the risk of prostate cancer (15607). Clinical research also shows that taking folic acid 1 mg daily increase the absolute risk of prostate cancer by 6.4% over a 10-year period when compared with placebo. However, those with a higher baseline dietary intake of folic acid had a lower rate of prostate cancer, but this was not statistically significant. Also, folate and folic acid intake in patients with prostate cancer is not associated with the risk of prostate cancer recurrence after radical prostatectomy (91317). However, it is possible that discrepancies are due to dietary folate versus folic acid intake. Large analyses of population studies suggest that while dietary folate/folic acid is not associated with prostate cancer, high blood folate/folic acid increases the risk of prostate cancer (50411,91316).
Additional clinical research shows that taking folic acid 800 mcg daily, in combination with vitamin B12 400 mcg, significantly increases the risk of developing cancer, especially lung cancer, and all-cause mortality in patients with cardiovascular disease (17041). However, this may be due to vitamin B12, as other observational research found that higher vitamin B12 levels are linked with an increased risk for lung cancer (102383). Meta-analyses of large supplementation trials of folic acid at levels between 0.5-2.5 mg daily also suggest an increased risk of cancer (50497,110318). Also, in elderly individuals, taking folic acid 400 mcg daily with vitamin B12 500 mcg daily increased the risk of cancer. The risk was highest in individuals over 80 years of age and in females and mainly involved gastrointestinal and colorectal cancers (90393).
Not all researchers suspect that high intake of folic acid supplements might be harmful. Some research suggests that increased dietary intake of folic acid, along with other nutrients, might be protective against cancer (16822). A meta-analysis of multiple clinical trials suggests that folic acid supplementation studies with folic acid levels between 500 mcg to 50 mg/day does not increase the risk of general or site-specific cancer for up to 7 years (91312,91321). Also, a post-hoc subgroup analysis of results from clinical research in adults with a history of recent stroke or ischemic attack suggests that taking folic acid, vitamin B12, and vitamin B6 does not increase cancer risk overall, although it was associated with an increased risk of cancer in patients who also had diabetes (90378).
Psychiatric ...Orally, folic acid 15 mg daily can sometimes cause exacerbation of seizure frequency and psychotic behavior (15).
Pulmonary/Respiratory ...Folic acid use in late pregnancy has been associated with an increased risk of persistent and childhood asthma at 3. 5 years in population research (50380). When taken pre-pregnancy or early in pregnancy, population research has not found an association with increased risk of asthma or allergies in childhood (90799,103979). Folic acid use in pregnancy has been associated with a slightly increased risk of wheeze and lower respiratory tract infections up to 18 months of age in population research (50328).