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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abortion. Although there is interest in using oral oleander for abortion, there is insufficient reliable information about the clinical effects of oleander for this condition.
• Asthma. Although there is interest in using oral oleander for asthma, there is insufficient reliable information about the clinical effects of oleander for this condition.
• Cancer. Although there is interest in using oral oleander for cancer, there is insufficient reliable information about the clinical effects of oleander for this condition.
• Heart failure. Although there is interest in using oral oleander for heart failure, there is insufficient reliable information about the clinical effects of oleander for this condition.
• Dysmenorrhea. Although there is interest in using oral oleander for dysmenorrhea, there is insufficient reliable information about the clinical effects of oleander for this condition.
• Epilepsy. Although there is interest in using oral oleander for epilepsy, there is insufficient reliable information about the clinical effects of oleander for this condition.
• Malaria. Although there is interest in using oral oleander for malaria, there is insufficient reliable information about the clinical effects of oleander for this condition.
• Tinea corporis. Although there is interest in using oral oleander for tinea corporis, there is insufficient reliable information about the clinical effects of oleander for this condition.
• Warts. Although there is interest in using topical oleander for warts, there is insufficient reliable information about the clinical effects of oleander for this condition.

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POSSIBLY EFFECTIVE

• Hypercholesterolemia. Most clinical research shows that oral pectin at a dose of 15 grams daily can slightly lower total cholesterol and low-density lipoprotein (LDL) cholesterol levels in patients with hypercholesterolemia. Details: While some small studies in patients with or without hypercholesterolemia suggest that pectin 1-12 grams daily for up to 12 weeks does not reduce lipid levels (2215,2217), other research in patients with hypercholesterolemia shows that taking pectin 15 grams daily for 4 weeks consistently reduces total cholesterol and LDL cholesterol by around 7% to 10% when compared with baseline or placebo (2214,2216,92473). Some forms of pectin might lower cholesterol levels better than others. Pectin with a higher molecular weight and higher degree of esterification appears to be the most effective (92473). A larger clinical study also shows that taking 20 grams of pectin and guar gum, along with small amounts of insoluble fiber, reduces total cholesterol by nearly 8% and LDL cholesterol by nearly 11%, but does not improve high-density lipoprotein (HDL) cholesterol or triglycerides, when compared with placebo (12547).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Colorectal cancer. Although there has been interest in using oral pectin for the prevention of colorectal cancer, there is insufficient reliable information about the clinical effects of pectin for this purpose.
• Diarrhea. It is unclear if oral pectin is beneficial in children with persistent diarrhea. Details: A small clinical study in children aged 5-12 months in developing nations with persistent diarrhea shows that taking pectin 4 grams/kg reduces the duration of diarrhea and vomiting, and reduces the need for oral rehydration solution and intravenous fluid, when compared with a rice-diet control (12575). Pectin has also been evaluated in combination with other ingredients. One clinical study in children aged 6 months to 6 years with acute diarrhea shows that taking a combination of apple pectin and chamomile (Diarrhoesan, Dr. Loges + Co. GmbH) for up to 5 days reduces the frequency of stools by day 3 by about 1.36-fold when compared with placebo, with improvements maintained through day 5. This combination product was given hourly up to a maximum dose of 50 mL in children 6-12 months of age, 60 mL in children 1-3 years of age, and 80 mL in children 4-6 years of age (19705). It is unclear if these findings are due to pectin, chamomile, or the combination.
• Gastroesophageal reflux disease (GERD). It is unclear if oral pectin is beneficial in children with GERD. Details: A small clinical study in children with GERD and cerebral palsy shows that adding pectin to enteral nutrition in a 1:2 ratio for 4 weeks might reduce some symptoms of GERD. The number of vomiting episodes per week was reduced by 60% and the frequency of coughing/wheezing was reduced by 76% for children given the pectin diet when compared with those given a non-pectin diet (92476).
• Impaired glucose tolerance (Prediabetes). It is unclear if oral pectin is beneficial in patients with impaired glucose tolerance. Details: A small clinical study in middle-aged patients with impaired glucose tolerance or impaired fasting glucose shows that drinking 400 mL of a beverage containing 40 grams/L of sugar beet pectin in two divided doses daily for 12 weeks does not improve fasting or postprandial plasma glucose concentrations or serum lipid levels when compared to baseline (34118).
• Irritable bowel syndrome (IBS). Although there has been interest in using oral pectin for IBS, there is insufficient reliable information about the clinical effects of pectin for this purpose.
• Mercury toxicity. It is unclear if oral pectin is beneficial in patients with mercury toxicity. Details: A small clinical study in children with mercury poisoning shows that taking pectin 2.5 grams daily for 21 days and then 5 grams daily for 39 days increases mercury excretion in the urine, decreases the duration of mercury toxicity, and improves psychological symptoms when compared to baseline (31657). The validity of these findings is limited by the lack of a comparator group.
• Niacin-induced flushing. It is unclear if oral pectin is beneficial for the prevention or management of niacin-induced flushing. Details: A small clinical study shows that taking apple pectin 2 grams 30 minutes prior to taking niacin extended-release 1000 mg reduces the duration of flushing by about 35 minutes when compared with placebo. However, apple pectin does not reduce the incidence of flushing, the time to flush, or the maximum severity of flushing (92477).
• Peptic ulcers. It is unclear if oral pectin is beneficial for the prevention of peptic ulcers. Details: A small clinical study in patients with recently healed duodenal ulcers shows that taking apple pectin 10 grams twice daily for 6 months does not reduce the recurrence of duodenal ulcers when compared with placebo (31697).
• Prostate cancer. It is unclear if oral pectin is beneficial in patients with prostate cancer. Details: Two small clinical studies in patients with prostate cancer show that taking a specific modified citrus pectin product (Pectasol, Econugenics) 4.8 grams three times daily following prostatectomy, radiation, or cryosurgery for up to one year slows disease progression and increases the time to prostate specific antigen (PSA) doubling when compared to baseline (15020,108525). The validity of these findings is limited by the lack of a comparator group.
• Radiation exposure. Although there has been interest in using oral pectin to minimize exposure to environmental radiation, there is insufficient reliable information about the clinical effects of pectin for this purpose. More evidence is needed to rate pectin for these uses.

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POSSIBLY UNSAFE ...when applied topically to broken or raw skin. Topical use of a paste containing multiple ingredients including oleander on broken or raw skin has caused bradycardia (94434).

LIKELY UNSAFE ...when used orally. Ingestion of oleander leaf, oleander leaf tea, or oleander seed has led to fatal and non-fatal poisonings (9,3495,65395,65407,65409,65410,65420,65422,65436,65437),(65438,94417,94428,94429,94430,94431,94432,94433,94434,94435),(94436,94437,103238,103239,103240,103241). A safe dose has not been identified, and as few as 2 seeds can cause fatal poisoning (106426).

CHILDREN: LIKELY UNSAFE
when used orally. Ingestion of oleander leaf, oleander leaf tea, or oleander seed has led to fatal and non-fatal poisonings (65395,65411,65419,65433,65434,65442,65444).

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally. Oleander has been reported to have abortifacient properties (5000). Also, maternal ingestion of oleander seeds during pregnancy has led to fetal toxicity (65425). There is insufficient reliable information available about the safety of topical use of oleander during pregnancy and lactation; avoid using.

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LIKELY SAFE ...when used in amounts commonly found in foods. Pectin has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally in amounts greater than those typically found in food. Pectin 4.8 grams three times daily has been used for up to one year without serious adverse effects (12547,15019,15020,92481,108525).

CHILDREN: POSSIBLY SAFE
when used orally in amounts greater than those found in food, short-term. Pectin 4 grams/kg has been used daily for up to 7 days without reports of serious adverse effects (12575,19705).

PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts commonly found in foods. Pectin has Generally Recognized as Safe (GRAS) status in the US (4912).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally in medicinal amounts (12577).

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CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, using oleander with prolonged corticosteroid therapy can increase the risk of oleander toxicity.  Details Oleander contains cardiac glycosides. Concomitant use of corticosteroids with oleander can increase the therapeutic and adverse effects of long-term corticosteroid use due to potassium depletion and electrolyte imbalance (2).

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of digoxin and oleander will increase the risk and severity of toxic effects.  Details Oleander contains cardiac glycosides similar to digoxin, increasing the risk of additive effects with concomitant use (2).

DIURETIC DRUGS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, diuretic drugs may increase the risk of oleander toxicity.  Details Concomitant use of potassium depleting diuretics and oleander can increase the risk of cardiac glycoside toxicity due to potassium depletion (506).

MACROLIDE ANTIBIOTICS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, macrolide antibiotics may increase the risk of oleander toxicity.  Details Macrolide antibiotics reduce levels of bacteria in the gut that break down digoxin to inactive metabolites, increasing digoxin bioavailability (17). Theoretically, this same process could increase the bioavailability of cardiac glycosides in oleander, increasing its toxicity.

QUININE Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, quinine may increase the risk of oleander toxicity.  Details Quinine is known to increase plasma levels of digoxin by inhibiting an efflux pump. This interaction might occur with other cardiac glycosides, including those in oleander (506).

STIMULANT LAXATIVES Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, stimulant laxatives may increase the risk of oleander toxicity.  Details Overuse or misuse of stimulant laxatives leads to potassium depletion. This might increase the risk of toxicity with cardiac glycosides, including those in oleander (2).

TETRACYCLINE ANTIBIOTICS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, tetracycline antibiotics may increase the risk of oleander toxicity.  Details Tetracycline antibiotics reduce levels of bacteria in the gut that break down digoxin to inactive metabolites, increasing digoxin bioavailability (17). Theoretically, this same process might increase the bioavailability of cardiac glycosides in oleander, increasing its toxicity.

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DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, pectin might reduce the absorption of digoxin, potentially decreasing its effectiveness.  Details A small clinical study shows that taking digoxin with a kaolin-pectin suspension reduces the absorption of digoxin by about 62% (2212). It is unclear if these effects are due to pectin, kaolin, or the combination.

LOVASTATIN (Mevacor) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, pectin might reduce the absorption of lovastatin, potentially decreasing its effectiveness.  Details Case reports suggest that concomitant use of pectin and lovastatin might reduce the cholesterol-lowering effect of lovastatin, possibly due to reduced intestinal absorption of lovastatin (615).

TETRACYCLINE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, pectin might reduce the absorption of tetracycline antibiotics, potentially decreasing their effectiveness.  Details A small clinical study shows that taking tetracycline with bismuth subsalicylate in a kaolin-pectin suspension reduces the absorption of tetracycline by about 34% (2213). It is unclear if these effects are due to pectin, kaolin, bismuth subsalicylate, or the combination.

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General ...Oleander can cause significant toxicity by any route of administration.
Most Common Adverse Effects:
Orally: Abdominal pain, bitter taste, diarrhea, headache, mucous membrane irritation, nausea, salivation, stupor, and vomiting.
Topically: Contact dermatitis.
Serious Adverse Effects (Rare):
Orally: Arrhythmias, cardiac arrest, cardiovascular collapse, death, hyperchloremia, hyperkalemia, metabolic acidosis, mydriasis, peripheral neuritis, and vision disturbances.

Cardiovascular ...Orally, oleander can cause malignant dysrhythmias, ventricular ectopy, cardiovascular collapse, cardiac arrest, and death (17,94437,103238,103239). Oleander can also cause hyperkalemia (2532,3495,65419,65435,94429,94436,94437,103239,103241). Hyperkalemia after oleander ingestion is generally due to inhibition of the sodium-potassium ATPase pump. Digoxin is usually detectable by radioimmunoassay, due to the cross-reactivity between digoxin and the cardiac glycosides contained in oleander (98220).
Topically, applying an oleander paste to penile and perianal ulcers has caused asymptomatic bradycardia. The paste contained oleander bark and leaves, as well as holy basil, tamarind, onion, and neem. There is also one case report of bradycardia requiring atropine treatment and a pacemaker after application of this paste to a penile ulcer. The risk of transcutaneous absorption of oleander is increased if applied to raw or broken skin (94434).

Dermatologic ...Topically, the sap of freshly cut oleander leaves can cause contact dermatitis (5000,65432,65448). In a case report, a 5-year-old child applied oleander leaves to the face and developed skin erythema, followed by blistering, swelling and partial thickness facial burns. The condition resolved with conservative management (106425).

Gastrointestinal ...Orally, oleander leaves, flowers, and seeds have a bitter taste, and can cause a burning sensation in the mouth, nausea, vomiting, and diarrhea (17,18,3495,65395,65411,65419,65422,65423,65431,65437,94417,94430,94432,94435,94436,98220,103239,103241). Oleander can also cause mucous membrane irritation, increased salivation, abdominal pain and cramping, and buccal erythema (3495,5000,65422,94435,94436,98220,103239). In one case report, a male with schizoaffective disorder consumed the leaves of an ornamental oleander plant, resulting in severe diarrhea and diarrhea-induced hypokalemia (94430).

Hematologic ...Oleander use has been associated with thrombocytopenia. A 33-year-old female who ingested an infusion of 20 oleander leaves presented with symptoms of oleander poisoning and, 72 hours after ingestion, developed thrombocytopenia. Another case of thrombocytopenia linked to oleander intake has also been reported (103241).

Hepatic ...Two cases of jaundice, increased bilirubin, and hepatosplenomegaly have been reported after oleander ingestion (65420).
Intramuscularly, there is one case report of a patient with cancer who developed hepatotoxicity after receiving daily injections of a specific oleander extract (Anvirzel, Phoenix Biotech) 1.2 mL/m2 for 2 months. Other causes of hepatotoxicity were ruled out (94428).

Neurologic/CNS ...Orally, oleander can cause weakness, headache, giddiness, dizziness, and malaise or stupor (17,18,3495,65422,65434,65443,65444,94417,94432,94435,94436,98220,103239). It can also cause peripheral neuritis (3495,5000) and numbness of the mouth or tongue (65422,94429). There is one case report of a young child who developed irritability and seizures after ingestion of oleander (65444). In another case, a 12-year-old child developed hypertonia, neck stiffness, and flexor plantar response after ingestion of oleander seeds (65434).

Ocular/Otic ...Orally, oleander can cause visual disturbances and mydriasis (3495,5000). In one case report, a 7-year-old child experienced a change in color vision about 6 hours after ingestion of oleander seeds (65411). There is also a report of dimness of vision and tinnitus after ingesting a water extract from oleander leaves (65424).

Renal ...Orally, oleander can cause acute kidney failure characterized by dark colored, scanty urine (less than 300 mL daily) (65417,65420,106426).

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General ...Orally, pectin seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, gas, loose stools, and mild cramps.
Serious Adverse Effects (Rare):
All routes of administration: Allergic reactions, including anaphylaxis, in sensitive individuals.

Gastrointestinal ...Orally, pectin alone or in combination with guar gum and insoluble fiber can cause gastrointestinal adverse effects such as mild cramps, diarrhea, gas, and loose stools (12547,15020,92473).

Immunologic ...Orally and topically, pectin may cause allergic reactions in sensitive individuals. In one case, a 7-year-old boy with a history of oral allergy syndrome after consuming a pectin-containing beverage experienced anaphylaxis after taking a citrus bath containing pectin. Allergy testing confirmed sensitivity to pectin (106928).

Pulmonary/Respiratory ...The occupational inhalation of pectin dust can cause asthma (580,581,582,583,584).

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