The Fluoroquinolone Toxicity Research Foundation

 
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Vitamins and Supplements Research                  See downloads for: Adobe Files



Illnesses and Injuries Associated With the Use of Selected Dietary Supplements

Products marketed as "dietary supplements" include a diverse range of products, from traditional nutrients, such as vitamins or minerals, to such substances as high-potency free amino acids, botanicals, enzymes, animal extracts, and bioflavanoids that often have no scientifically recognized role in nutrition.

There is currently no systematic evaluation of the safety of products marketed as dietary supplements. Dietary supplements routinely enter the marketplace without undergoing a safety review by FDA. Published studies on the safety of these products are extremely sparse. There is no systematic collection and review of adverse reaction reports for dietary supplements, as there is for drugs, and physicians rarely seek information about their patients' use of dietary supplements. Despite the lack of any system for gaining information about the risks of dietary supplements, an increased number of reports of adverse reactions to dietary supplement products has recently been recognized. Because of concern about these products, FDA has, in the last year, initiated an effort to collect and evaluate existing studies and case reports on safety problems associated with dietary supplements. As a result of that effort, FDA has begun to identify dietary supplements for which serious adverse reactions have been documented. A list of selected dietary supplements associated with serious safety problems follows. This list is not intended to include all hazardous ingredients in dietary supplements.

Vitamins and Minerals
Vitamin and mineral dietary supplements have a long history of use at levels consistent with the Recommended Dietary Allowances (RDA's) or at low multiples of the RDA's, and are generally considered safe at these levels for the general population. Intakes above the RDA, however, vary widely in their potential for adverse effects. Certain vitamins and minerals that are safe when consumed at low levels are toxic at higher doses. The difference between a safe low dose and a toxic higher dose is quite large for some vitamins and minerals and quite small for others.

A. Vitamin A
Vitamin A is found in several forms in dietary supplements. Preformed vitamin A (vitamin A acetate and vitamin A palmitate) has well-recognized toxicity when consumed at levels of 25,000 International Units (IU) per day, or higher. (Beta-carotene does not have the potential for adverse effects that the other forms of vitamin A do, because high intakes of beta-carotene are converted to vitamin A in the body at much lower levels). The RDA for vitamin A is 1,000 retinol equivalents (RE) for men, which is equivalent to 3,300 IU of preformed vitamin A, and 80 percent of these amounts for women.
The adverse effects associated with consumption of vitamin A at 25,000+ IU include severe liver injury (including cirrhosis), bone and cartilage pathologies, elevated intracranial pressure, and birth defects in infants whose mothers consumed vitamin A during pregnancy. Groups especially vulnerable to vitamin A toxicity are children, pregnant women, and those with liver disease caused by a variety of factors, including alcohol, viral hepatitis, and severe protein-energy malnutrition.
There are some studies that suggest vitamin A toxicity has occurred at levels of ingestion below 25,000 IU. In addition, the severity of the injuries that occur at 25,000 IU suggests that substantial, but less severe and less readily recognized, injuries probably occur at somewhat lower intakes. Most experts recommend that vitamin A intake not exceed 10,000 IU for most adults or 8,000 IU for pregnant and nursing women.

B. Vitamin B6
Neurologic toxicity, including ataxia (alteration in balance) and sensory neuropathy (changes in sensations due to nerve injury), is associated with intake of vitamin B6 (pyridoxine) supplements at levels above 100 milligrams per day. As little as 50 milligrams per day has caused resumption of symptoms in an individual previously injured by higher intakes. The RDA for vitamin B6 is 2 milligrams. Vitamin B6 is marketed in capsules containing dosages in the 100-, 200-, and 500-milligrams range.

C. Niacin (nicotinic acid and nicotinamide)
Niacin taken in high doses is known to cause a wide range of adverse effects. The RDA for niacin is 20 milligrams. Niacin is marketed in dietary supplements at potencies of 250 mg, 400 mg, and 500 mg, in both immediate and slow-release formulations. Daily doses of 500 mg from slow-release formulations, and 750 mg of immediate-release niacin, have been associated with severe adverse reactions, including gastrointestinal distress (burning pain, nausea, vomiting, bloating, cramping, and diarrhea) and mild to severe liver damage. Less common, but more serious (in some cases life-threatening), reactions include liver injury, myopathy (muscle disease), maculopathy of the eyes (injury to the eyes resulting in decreased vision), coagulopathy (increased bleeding problems), cytopenia (decreases in cell types in the blood), hypotensive myocardial ischemia (heart injury caused by too low blood pressure), and metabolic acidosis (increases in the acidity of the blood and urine).
Niacin (nicotinic acid) is approved as a prescription drug to lower cholesterol. Many of the observed adverse reactions have occurred when patients have switched to OTC formulations of niacin, and particularly when they have switched from immediate-release formulations to dietary supplements containing slow-release niacin formulations without the knowledge of their physicians.

D. Selenium
Selenium is a mineral found in dietary supplement products. At high doses (approximately 800 to 1,000 micrograms per day), selenium can cause tissue damage, especially in tissues or organs that concentrate the element. The toxicity of selenium depends upon the chemical form of selenium in the ingested supplement and upon the selenium levels in the foods consumed. Human injuries have occurred following ingestion of high doses over a few weeks.

Herbals
Herbal and other botanical ingredients of dietary supplements include processed or unprocessed plant parts (bark, leaves, flowers, fruits, and stems), as well as extracts and essential oils. They are available in a variety of forms, including water infusions (teas), powders, tablets, capsules, and elixirs, and may be marketed as single substances or in combination with other materials, such as vitamins, minerals, amino acids, and non-nutrient ingredients. Although data on the availability, consumer use, and health effects of herbals are very limited, some herbal ingredients have been associated with serious adverse health effects.

A. Chaparral (Larrea tridentata)
Chaparral, commonly called the creosote bush, is a desert shrub with a long history of use as a traditional medicine by Native Americans. Chaparral is marketed as a tea, as well as in tablet, capsule, and concentrated extract form, and has been promoted as a natural antioxidant "blood purifier," cancer cure, and acne treatment. At least six cases (five in the United States and one in Canada) of acute non-viral hepatitis (rapidly developing liver damage) have been associated with the consumption of chaparral as a dietary supplement. Additional cases have been reported and are under investigation. In the majority of the cases reported thus far, the injury to the liver resolves over time, after discontinuation of the product. In at least two patients, however, there is evidence that chaparral consumption caused irreversible liver damage. One patient suffered terminal liver failure requiring liver transplant.
Most of these cases are associated with the consumption of single ingredient chaparral capsules or tablets; however, a few of the more recent cases appear to be associated with consumption of multi-ingredient products (capsules, tablets or teas) that contain chaparral as one ingredient. Chemical analyses have identified no contaminants in the products associated with the cases of hepatitis. Products from at least four different distributors and from at least two different sources have been implicated thus far.
After FDA's health warning, many distributors of chaparral products voluntarily removed the products from the market in December of 1992. Some chaparral products remain on the market, however, and other distributors who removed their products from the market are seeking to clarify the status of these products.

B. Comfrey (Symphytum officinale (common comfrey), S. asperum (prickly comfrey), S. X uplandicum (Russian comfrey))
Preparations of comfrey, a fast-growing leafy plant, are widely sold in the United States as teas, tablets, capsules, tinctures, medicinal poultices, and lotions. Since 1985, at least seven cases of hepatic veno-occlusive disease--obstruction of blood flow from the liver with potential scarring (cirrhosis)--including one death, have been associated with the use of commercially available oral comfrey products.
Comfrey, like a number of other plants (e.g., Senecio species), contains pyrrolizidine alkaloids. The toxicity of pyrrolizidine alkaloids to humans is well-documented. Hepatic veno-occlusive disease following ingestion of pyrrolizidine alkaloid-containing products, has been documented repeatedly throughout the world. Hepatic veno-occlusive disease is usually acute and may result in fatal liver failure. In less severe cases, liver disease may progress to a subacute form. Even after apparent recovery, chronic liver disease, including cirrhosis, has been noted. Individuals who ingest small amounts of pyrrolizidine alkaloids for a prolonged period may also be at risk for development of hepatic cirrhosis. The diagnosis of pyrrolizidine alkaloid-induced hepatic veno-occlusive disease is complex, and the condition is probably underdiagnosed.
The degree of injury caused by pyrrolizidine alkaloid-containing plants, like comfrey, is probably influenced by such factors as the age of the user, body mass, gender, and hepatic function, as well the total cumulative dose ingested and the type of exposure (i.e., whether exposure was to leaves or roots, infusions or capsules). Infants in general appear to be particularly susceptible to adverse effects of exposure to pyrrolizidine alkaloids; there are reports of infants developing hepatic veno-occlusive disease following acute exposure of less than one week. Transplacental pyrrolizidine poisoning has been suggested by the occurrence of hepatic disease in the newborn infant of a woman who consumed herbal tea during pregnancy.
Although liver damage is the major documented form of injury to humans from pyrrolizidine alkaloid-containing herbals, animal studies suggest that their toxicity is much broader. Animals exposed to pyrrolizidine alkaloids have developed a wide range of pulmonary, kidney and gastro-intestinal pathologies. Pyrrolizidine alkaloid-containing plants, including comfrey, have also been shown to cause cancer in laboratory animals.
Four countries (the United Kingdom, Australia, Canada, and Germany) have recently restricted the availability of products containing comfrey, and other countries permit use of comfrey only under a physician's prescription.

C. Yohimbe (Pausinystalia yohimbe)
Yohimbe is a tree bark containing a variety of pharmacologically active chemicals. It is marketed in a number of products for body building and "enchanced male performance." Serious adverse effects, including renal failure, seizures and death, have been reported to FDA with products containing yohimbe and are currently under investigation.
The major identified alkaloid in yohimbe is yohimbine, a chemical that causes vasodilation, thereby lowering blood pressure. Yohimbine is also a prescription drug in the United States. Side effects are well recognized and may include central nervous system stimulation that causes anxiety attacks. At high doses, yohimbine is a monoamine oxidase (MAO) inhibitor. MAO inhibitors can cause serious adverse effects when taken concomitantly with tyramine-containing foods (e.g., liver, cheeses, red wine) or with over-the-counter (OTC) products containing phenylpropanolamine, such as nasal decongestants and diet aids. Individuals taking yohimbe should be warned to rigorously avoid these foods and OTC products because of the increased likelihood of adverse effects.
Yohimbe should also be avoided by individuals with hypotension (low blood pressure), diabetes, and heart, liver or kidney disease. Symptoms of overdosage include weakness and nervous stimulation followed by paralysis, fatigue, stomach disorders, and ultimately death.

D. Lobelia (Lobelia inflata)
Lobelia, also known as Indian tobacco, contains pyridine-derived alkaloids, primarily lobeline. These alkaloids have pharmacological actions similar to, although less potent than, nicotine. There have been several reported cases of adverse reactions associated with consumption of dietary supplements containing lobelia.
Depending on the dose, lobeline can cause either autonomic nervous system stimulation or depression. At low doses, it produces bronchial dilation and increased respiratory rate. Higher doses result in respiratory depression, as well as sweating, rapid heart rate, hypotension, and even coma and death. As little as 50 milligrams of dried herb or a single milliliter of lobelia tincture has caused these reactions.
Because of its similarity to nicotine, lobelia may be dangerous to susceptible populations, including children, pregnant women, and individuals with cardiac disease. Lobelia is nevertheless found in dietary supplement products that are marketed for use by children and infants, pregnant women, and smokers.

E. Germander (Teucrium genus)
Germander is the common name for a group of plants that are contained in medicinal teas, elixirs and capsules or tablets, either singly or in combination with other herbs, and marketed for the treatment of obesity and to facilitate weight loss.
Since 1986, at least 27 cases of acute nonviral hepatitis (liver disease), including one death, have been associated with the use of commercially available germander products in France. These cases show a clear temporal relationship between ingestion of germander and onset of hepatitis, as well as the resolution of symptoms when the use of germander was stopped. In 12 cases, re-administration of germander was followed by prompt recurrence of hepatitis. Recovery occurred gradually in most cases, approximately two of six months after withdrawal of germander. Analyses of these cases does not indicate a strong relationship between the dosage or duration of ingestion and the occurrence of hepatitis.
Although the constituent in germander responsible for its hepatic toxicity has not been identified, germander contains several chemicals, including polyphenols, tannins, diterpenoids, and flavonoids.
On the basis of the 27 French hepatitis cases, the French Ministry of Health has forbidden the use of germander in drugs. Its use has been restricted in other countries.

F. Willow Bark (Salix species)
Willow bark has long been used for its analgesic (pain killing), antirheumatic, and antipyretic (fever-reducing) properties. Willow bark is widely promoted as an "aspirin-free" analgesic, including in dietary supplement products for children. Because it shares the same chemical properties and the same adverse effects as aspirin, this claim is highly misleading. The "aspirin-free" claim is particularly dangerous on products marketed, without warning labels, for use by children and other aspirin-sensitive individuals.
The pharmacologically active component in willow bark is "salicin," a compound that is converted to salicylic acid by the body after ingestion. Both willow bark and aspirin are salicylates, a class of compounds that work by virtue of their salicylic acid content. Aspirin (acetylsalicylic acid) is also converted to salicylic acid after ingestion.
All salicylates share substantially the same side effects. The major adverse effects include irritation of the gastric mucosa (a particular hazard to individuals with ulcer disease), adverse effects when used during pregnancy (including stillbirth, bleeding, prolonged gestation and labor, and low-birth-weight infants), stroke, and adverse effects in children with fever and dehydration. Children with influenza or chickenpox should avoid salicylates because their use, even in small doses, is associated with development of Reye syndrome, which is characterized by severe, sometimes fatal, liver injury. Salicylate intoxication (headache, dizziness, ringing in ears, difficulty hearing, dimness of vision, confusion, lassitude, drowsiness, sweating, hyperventilation, nausea, vomiting, and central nervous system disturbances in severe cases) may occur as the result of over-medication, or kidney or liver insufficiency. Hypersensitivity, manifested by itching, broncho-spasm and localized swelling (which may be life-threatening), can occur with very small doses of salicylates, and may occur even in those without a prior history of sensitivity to salicylates. Approximately 5 percent of the population is hypersensitive to salicylates.

G. Jin Bu Huan
Jin Bu Huan is a Chinese herbal product whose label claims that it is good for "insomnia due to pain," ulcer, "stomachic sic| neuralgia, pain in shrunken womb after childbirth, nervous insomnia, spasmodic cough, and etc." Jin Bu Huan has been recently reported to be responsible for the poisoning of at least three young children (ages 13 months to 2 2 years), who accidentally ingested this product. The children were hospitalized with rapid-onset, life-threatening bradycardia (very low heart rate), and central nervous system and respiratory depression. One child required intubation (assisted breathing). All three utlimately recovered following intensive medical care.
Although the product label identified the plant source for Jin Bu Huan as Polygala chinensis, this appears to be incorrect since preliminary analyses indicate the presence of tetrahydropalmatine (THP), a chemical not found in Polygala. THP is found, however, in high concentrations in plants of certain Stephania species. In animals, exposure to THP results in sedation, analgesia, and neuromuscular blockade (paralysis). The symptoms of the three children are consistent with these effects.
An additional case of THP toxicity, reported in the Netherlands, appears to be associated with the same product, and is being investigated.

H. Herbal products containing Stephania and Magnolia species
A Chinese herbal preparation containing Stephania and Magnolia species that was sold as a weight-loss treatment in Belgium has been implicated recently as a cause of severe kidney injury in at least 48 women. These cases were only discovered by diligent investigations by physicians treating two young women who presented with similar cases of rapidly progressing kidney disease that required renal dialysis. Once it was determined that both these women had used the herbal diet treatment, further investigation of kidney dialysis centers in Belgium found a total of 48 individuals with kidney injury who had used the herbal product.
At the time that a report of these adverse effects was published in February 1993, 18 of the 48 women had terminal kidney failure that will require either kidney transplantation or life-long renal dialysis.

I. Ma huang
Ma huang is one of several names for herbal products containing members of the genus Ephedra. There are many common names for these evergreen plants, including squaw tea and Mormon tea. Serious adverse effects, including hypertension (elevated blood pressure), palpitation (rapid heart rate), neurophathy (nerve damage), myopathy (muscle injury), psychosis, stroke, and memory loss, have been reported to FDA with products containing Ma huang as ingredients and are currently under investigation.
The Ephedras have been shown to contain various chemical stimulants, including the alkaloids ephedrine, pseudoephedrine and norpseudoephedrine, as well as various tannins and related chemicals. The concentrations of these alkaloids depends upon the particular species of Ephedra used. Ephedrine and pseudoephedrine are amphetamine-like chemicals used in OTC and prescription drugs. Many of these stimulants have known serious side effects.
Ma huang is sold in products for weight control, as well as in products that boost energy levels. These products often contain other stimulants, such as caffeine, which may have synergistic effects and increase the potential for adverse effects.

Amino Acids
Amino acids are the individual constituent parts of proteins. Consumption of foods containing intact proteins ordinarily provides sufficient amounts of the nine amino acids needed for growth and development in children and for maintenance of health of adults. The safety of amino acids in this form is generally not a concern. When marketed as dietary supplements, amino acids are sold as single compounds, in combinations of two or more amino acids, as components of protein powders, as chelated single compounds, or in chelated mixtures. Amino acids are promoted for a variety of uses, including body-building. Some are promoted for claimed pharmacologic effects.
The Federation of American Societies for Experimental Biology (FASEB) recently conducted an exhaustive search of available data on amino acids and concluded that there was insufficient information to establish a safe intake level for any amino acids in dietary supplements, and that their safety should not be assumed. FASEB warned that consuming amino acids in dietary supplement form posed potential risks for several subgroups of the general population, including women of childbearing age (especially if pregnant or nursing), infants, children, adolescents, the elderly, individuals with inherited disorders of amino acid metabolism, and individuals with certain diseases.
At least two of the amino acids consumed in dietary supplements have also been associated with serious injuries in healthy adults.

A. L-tryptophan
L-tryptophan is associated with the most serious recent outbreak of illness and death known to be due to consumption of dietary supplements. In 1989, public health officials realized that an epidemic of eosinophilia-myalgia syndrome (EMS) was associated with the ingestion of L-tryptophan in a dietary supplement. EMS is a systemic connective tissue disease characterized by severe muscle pain, an increase in white blood cells, and certain skin and neuromuscular manifestations.
More than 1,500 cases of L-tryptophan-related EMS have been reported to the national Centers for Disease Control and Prevention. At least 38 patients are known to have died. The true incidence of L-tryptophan-related EMS is thought to be much higher. Some of the individuals suffering from L-tryptophan-related EMS have recovered, while other individuals' illnesses have persisted or worsened over time.
Although initial epidemiologic studies suggested that the illnesses might be due to impurities in an L-tryptophan product from a single Japanese manufacturer, this hypothesis has not been verified, and additional evidence suggests that L-tryptophan itself may cause or contribute to development of EMS. Cases of EMS and related disorders have been found to be associated with ingestion of L-tryptophan from other batches or sources of L-tryptophan. These illnesses have also been associated with the use of L-5-hydroxytryptophan, a compound that is closely related to L-tryptophan, but is not produced using the manufacturing process that created the impurities in the particular Japanese product.

B. Phenylalanine
A number of illnesses, including those similar to the eosinophilia myalgia syndrome (EMS) associated with L-tryptophan consumption, have been reported to FDA in individuals using dietary supplements containing phenylalanine. There are also published reports of scleroderma/scleroderma-like illnesses, which have symptoms similar to EMS, occurring in children with poorly controlled blood phenylalanine levels, as well as in those with phenylketonuria (PKU), a genetic disorder characterized by the inability to metabolize phenylalanine.

Other Products Marked as Dietary Supplements

A. Germanium
Germanium is a nonessential element. Recently, germanium has been marketed in the form of inorganic germanium salts and novel organogermanium compounds, as a "dietary supplement." These products are promoted for their claimed immunomodulatory effects or as "health-promoting" elixirs. Germanium supplements, when used chronically, have caused nephrotoxicity (kidney injury) and death. Since 1982, there have been 20 reported cases of acute renal failure, including two deaths, attributed to oral intakes of germanium elixirs. In surviving patients, kidney function has improved after discontinuation of germanium, but none of the patients have recovered normal kidney function.
One particular organogermanium compound, an azaspiran organogermanium, has been studied for its potential use as an anticancer drug. Forty percent of the patients in this study experienced transient neurotoxicity (nerve damage), and two patients developed pulmonary toxicity. Because of these side effects, medically supervised administration of this drug with monitoring for toxicity has been recommended for those using germanium chronically.


Side effects and toxicity of some vitamins and minerals.

Vitamin-caused symptoms may be secondary to those associated with additives
(e.g., mannitol), colorings, or binders;. The following are symptoms of
specific vitamin overdose: Underlying disease, medical conditions and
medications can interact with dietary supplements.

Vitamin A
Acute toxicity effects include headache, nausea, vomiting, drowsiness, and
desquamation after 24 hours.
Chronic toxicity affects the skin, mucous membranes, and the musculoskeletal
and neurological systems.
Skin and mucous membrane effects include erythema, eczema, pruritus, dry and
cracked skin, conjunctivitis, palmar and plantar peeling, and alopecia.
Musculoskeletal effects include pain and tenderness, particularly in the long
bones of the upper and lower extremities, which may be exacerbated by
exercise; epiphyseal capping and premature epiphyseal closure may occur in
children.
Neurological effects include frontal headache and blurred vision.
Findings also include papilledema, hepatomegaly, ascites, erythematous
dermatitis, or bulging fontanelle in infants.

Vitamin D
Acute toxicity effects may include muscle weakness, apathy, headache,
anorexia, nausea, vomiting, and bone pain.
Chronic toxicity effects include the above symptoms and constipation,
anorexia, polydipsia, polyuria, backache, hyperlipidemia, and hypercalcemia.
Findings also may include hypertension and cardiac arrhythmias.

Vitamin E
Acute toxicity effects include nausea, headache, fatigue, easy bruising, and
bleeding (lowered prothrombin time [PT], prolonged activated partial
thromboplastin time [aPTT]), diplopia (at dosages as low as 300 IU), muscle
weakness, and creatinuria.
Chronic toxicity effects include all of the above.

Vitamin K
This particular toxicity typically is associated with infants.
Effects may include jaundice in newborns, hemolytic anemia, and
hyperbilirubinemia.
Toxicity also blocks the effects of oral anticoagulants.

Vitamins B-1, B-2, B-12, and folate
Effects may be minimal and nonspecific.

Vitamin B-2 turns the urine yellow-orange.

Vitamin B-1 (ie, thiamine) toxicity effects may include the following:
Tachycardia
Hypotension
Cardiac dysrhythmias
Headache
Anaphylaxis
Vasodilation
Weakness
Convulsions
Single acute toxicity is rare.

Vitamin B-3 (ie, niacin, nicotinic acid)
Acute toxicity effects are prostaglandin-mediated and include flushing,
pruritus, wheezing, vasodilation, headache, increased intracranial blood
flow, and headache.
Chronic toxicity effects include jaundice, abnormal liver function tests,
signs and symptoms of liver toxicity (most common with sustained-release
preparations), and acanthosis nigricans (rare).

Vitamin B-6 (ie, pyridoxine)
Effects include tachypnea and sensory neuropathies, such as burning pains,
paresthesias, ataxia, clumsiness, paralysis, and perioral numbness.
Findings range from normal CNS function to progressive sensory ataxias,
profound impairment of position and vibration sense, and diminished tendon
reflexes.

Vitamin C
Effects may be renal colic (ie, nephrolithiasis), diarrhea, rebound scurvy in
infants born to women taking high doses, hemolysis if G-6-PD deficiency is
present, possible dental decalcification, and increased estrogen levels.
Findings may include occult rectal bleeding. Causes:

Vitamin A (ie, retinol) - Found in green and yellow vegetables, liver, egg
yolks, fish oil, and margarine
US recommended dietary allowance (RDA) is 5000 IU (2500 IU for children aged
1-4 years).
Supplements usually are 10,000-50,000 IU per capsule. Fish-liver oils may
contain more than 180,000 IU/g.
Acute toxic dose is 25,000 IU/kg, and chronic toxic dose is 4000 IU/kg every
day for 6-15 months.
Beta-carotene (ie, provitamin A) is converted to retinol but not rapidly
enough for acute toxicity. Vitamin A is highly teratogenic in pregnancy;
however, it also is a cofactor in night vision and bone growth.

Vitamin D (ie, cholecalciferol) is present in most dairy products, egg yolks,
liver, and fish.
RDA is 400 IU for persons older than 1 year.
Supplements usually are 400 IU per tablet.
Acute toxic dose is not established, and chronic toxic dose is more than
50,000 IU/d in adults. In children, 400 IU/d is potentially toxic. A wide
variance in potential toxicity exists.
Vitamin D increases serum calcium levels by facilitating calcium absorption
and mobilizing calcium from bone.

Vitamin E (ie, alpha-tocopherol) is found in vegetable oil, nuts, wheat, and
green leafy vegetables.
RDA is 30 IU (10 IU for children aged 1-4 years).
Supplements usually are 100-1000 IU per capsule.
The potentially toxic dose is more than 3000 IU/d for 7-9 weeks. Severe
toxicity is very rare.
Vitamin E functions as an antioxidant. It may block absorption of Vitamin A
and K. Vitamin E decreases low-density lipoprotein (LDL) cholesterol level at
doses more than 400 IU/d.

Vitamin K (ie, phytonadione)
Vitamin K-1 supplements usually are 2.5-10 mg.
A toxic dose amount is not established.
Phytonadione promotes liver synthesis of factors II, VII, IX, and X.

Vitamin B-1 (ie, thiamine) is found in organ meats, yeast, eggs, and green
leafy vegetables.
RDA is 1.5 mg (0.7 mg for children aged 1-4 years).
Supplements usually are 50-500 mg per tablet.
Thiamin generally is nontoxic.

Vitamin B-1 is a cofactor for pyruvate dehydrogenase in the Krebs cycle.
Vitamin B-2 (ie, riboflavin)
RDA is 1.7 mg (0.8 mg for children aged 1-4 years).
Supplements usually are 25-100 mg.
B-2 generally is nontoxic.

Vitamin B-3 (ie, niacin) is found in green vegetables, yeast (pumpernickel
bagels may contain 190 mg of niacin), animal proteins, fish, liver, and
legumes.
RDA is 20 mg (9 mg for children aged 1-4 years).
Supplements usually are 20-500 mg per tablet.
Toxic dose is more than 1000 mg/d.

Vitamin B-3 is converted to nicotinamide adenine dinucleotide (NAD) or
nicotinamide adenine dinucleotide phosphate (NADP), which are coenzymes for
dehydrogenase type reactions. In large doses, niacin decreases synthesis of
LDL cholesterol.

Vitamin B-6 (ie, pyridoxine) is found in poultry, fish, pork, grains, and
legumes.
RDA is 2 mg (0.7 mg for children aged 1-4 years).
Supplements usually are 5-500 mg per tablet.
Over time, 300-500 mg/d may be neurotoxic. Acute toxic dose generally is not
established.

Vitamin B-6 functions in protein and amino acid metabolism. Pyridoxine is the
treatment of choice for isoniazid overdose and is used for bodybuilding,
premenstrual syndrome, schizophrenia, childhood autism, and attention deficit
hyperactivity disorder (ADHD).

Vitamin B-12 (ie, cyanocobalamin) requires intrinsic factor for absorption.
RDA is 2 mcg (1 mcg for children aged 1-4 years).
Supplements usually are 25-250 mcg per tablet.
Toxic dose is not established.

Vitamin B-12 is a treatment for pernicious anemia and cyanide poisoning.

Vitamin C (ie, ascorbic acid) is found in citrus fruits and vegetables.
RDA is 60 mg (40 mg for children aged 1-4 years).
Supplements usually are 100-2000 mg per capsule.
Chronic toxic dose is more than 2 g/d.
Acute toxic dose is not determined.

Vitamin C is an antioxidant and reducing agent. Vitamin C is used to treat
(controversial) upper respiratory infections (URIs) and cancer.

Folic acid is found in leafy green vegetables and oranges.
RDA is 0.4 mg (0.2 mg in children aged 1-4 years).
Toxic dose is not established. Folic acid generally is nontoxic. Intakes more
than 5000 mcg/d mask pernicious anemia.
Folic acid decreases risk of neural tube defects and may decrease serum
homocysteine levels (coronary artery disease [CAD] risk factor).


Symptoms of magnesium toxicity can occur more likely if calcium intake is
low. These symptoms may include depression of the central nervous system,
causing muscle weakness, fatigue, sleepiness, or even hyperexcitability. In
extreme states, magnesium overload can cause death. high doses of magnesium
supplements, which may be added to laxatives, can promote adverse effects
such as diarrhea. Magnesium toxicity is more often associated with kidney
failure, when the kidney loses the ability to remove excess magnesium. Very
large doses of laxatives also have been associated with magnesium toxicity,
even with normal kidney functions Signs of excess magnesium can be similar to
magnesium deficiency and include mental status changes, nausea, diarrhea,
appetite loss, muscle weakness, difficulty breathing, extremely low blood
pressure, and irregular heartbeat.

An increase in the concentrations of sodium in the bloodstream can be toxic.
The normal concentration of sodium in the blood plasma is 136-145 mM, while
levels over 152 mM can result in seizures and death . Increased plasma
sodium, which is called hypernatremia , causes various cells of the body,
including those of the brain, to shrink. Shrinkage of the brain cells results
in confusion, coma , paralysis of the lung muscles, and death. Death has
occurred where table salt (sodium chloride) was accidently used, instead of
sugar, for feeding infants. Death due to sodium toxicity has also resulted
when baking soda (sodium bicarbonate) was used during attempted therapy of
excessive diarrhea or vomiting. Although a variety of processed foods contain
high levels of sodium chloride, the levels used are not enough to result in
sodium toxicity.

The normal level of potassium in the bloodstream is in the range of 3.5-5.0
mM, while levels of 6.3-8.0 mM (severe hyperkalemia) result in cardiac
arrhythmias or even death due to cardiac arrest. Potassium is potentially
quite toxic, however toxicity or death due to potassium poisoning is usually
prevented because of the vomiting reflex. The consumption of food results in
mild increases in the concentration of potassium in the bloodstream, but
levels of potassium do not become toxic because of the uptake of potassium by
various cells of the body, as well as by the action of the kidneys
transferring the potassium ions from the blood to the urine. The body's
regulatory mechanisms can easily be overwhelmed, however, when potassium
chloride is injected intravenously, as high doses of injected potassium can
easily result in death.

Iodine toxicity can result from an intake of 2.0 mg of iodide per day. The
toxicity results in impairment of the creation of thyroid hormone, resulting
in lower levels of thyroid hormone in the bloodstream. The thyroid gland
enlarges, as a consequence, and goiter is produced. This enlargement is also
called hyperthyroidism . Goiter is usually caused by iodine deficiency. In
addition to goiter, iodine toxicity produces ulcers on the skin. This
condition has been called "kelp acne ," because of its association with
eating kelp, an ocean plant, which contains high levels of iodine. Iodine
toxicity occurs in Japan, where large amounts of seaweed are consumed.

Iron toxicity is not uncommon, due to the wide distribution of iron pills. A
lethal dose of iron is in the range of 200-250 mg iron/kg body weight. Hence,
a child who accidently eats 20 or more iron tablets may die as a result of
iron toxicity. Within six hours of ingestion, iron toxicity can result in
vomiting, diarrhea, abdominal pain , seizures, and possibly coma. A latent
period, where the symptoms appear to improve, may occur but it is followed by
shock , low blood glucose, liver damage, convulsions, and death, occuring
12-48 hours after toxic levels of iron are ingested.
Nitrite poisoning should be considered along with iron toxicity, since
nitrite produces its toxic effect by reacting with the iron atom of
hemoglobin. Hemoglobin is an iron-containing protein that resides within the
red blood cells. This protein is responsible for the transport of nearly all
of the oxygen, acquired from the lungs, to various tissues and organs of the
body. Hemoglobin accounts for the red color of our red blood cells. A very
small fraction of our hemoglobin spontaneously oxidizes per day, producing a
protein of a slightly different structure, called methemoglobin. Normally,
the amount of methemoglobin constitutes less than 1% of the total hemoglobin.
Methemoglobin can accumulate in the blood as a result of nitrite poisoning.
Infants are especially susceptible to poisoning by nitrite.
Nitrate, which is naturally present in green leafy vegetables and in the
water supply is rapidly converted to nitrite by the naturally occurring
bacteria residing on our tongue, as well as in the intestines, and then
absorbed into the bloodstream. The amount of nitrate that is supplied by
leafy vegetables and in drinking water is generally about 100-170 mg/day. The
amount of nitrite supplied by a typical diet is much less, that is, than 0.1
mg nitrite/day. Poisoning by nitrite, or nitrate after its conversion to
nitrite, results in the inability of hemoglobin to carry oxygen throughout
the body. This condition can be seen by the blue color of the skin. Adverse
symptoms occur when over 30% of the hemoglobin has been converted to
methemoglobin, and these symptoms include cardiac arrhythmias, headache ,
nausea and vomiting, and in severe cases, seizures.

Calcium and phosphate are closely related nutrients. Calcium toxicity is
rare, but overconsumption of calcium supplements may lead to deposits of
calcium phosphate in the soft tissues of the body. Phosphate toxicity can
occur with overuse of laxatives or enemas that contain phosphate. Severe
phosphate toxicity can result in hypocalcemia , and in various symptoms
resulting from low plasma calcium levels. Moderate phosphate toxicity,
occurring over a period of months, can result in the deposit of calcium
phosphate crystals in various tissues of the body.

Zinc toxicity is rare, but it can occur in metal workers who are exposed to
fumes containing zinc. Excessive dietary supplements of zinc can result in
nausea, vomiting, and diarrhea. The chronic intake of excessive zinc
supplements can result in copper deficiency, as zinc inhibits the absorption
of copper.

Severe alterations in copper metabolism occur in two genetic diseases,
Wilson's disease and Menkes' disease. Both of these diseases are rare and
occur in about one in 100,000 births. Both diseases involve mutations in the
proteins that transport copper, that is, in special channels that allow the
passage of copper ions through cell membranes. Wilson's disease tends to
occur in teenagers and in young adults, and then remain for the lifetime.

Copper accumulates in the liver, kidney, and brain, resulting in damage to
the liver and nervous system. Wilson's disease can be successfully controlled
by lifelong treatment with d-penicillamine. Treatment also involves avoiding
foods that are high in copper, such as liver, nuts, chocolate, and mollusks.
After an initial period of treatment with penicillamine, Wilson's disease may
be treated with zinc (150 mg oral Zn/day). The zinc inhibits the absorption
of dietary copper.

Selenium toxicity occurs in regions of the world, including some parts of
China, where soils contain high levels of selenium. A daily intake of
0.75-5.0 mg selenium may occur in these regions, due to the presence of
selenium in foods and water. Early signs of selenium toxicity include nausea,
weakness, and diarrhea. With continued intake of selenium, changes in
fingernails and hair loss results, and damage to the nervous system occurs.
The breath may acquire a garlic odor, as a result of the increased production
of dimethylselenide in the body, and its release via the lungs.

Manganese toxicity occurs in miners in manganese mines, where men breath air
containing dust bearing manganese at a concentration of 5-250 mg/cubic meter.
Manganese toxicity in miners has been documented in Chile, India, Japan,
Mexico, and elsewhere. Symptoms of manganese poisoning typically occur within
several months or years of exposure. These symptoms include a mental disorder
resembling schizophrenia , as well as hyperirritability, violent acts,
hallucinations , and difficulty in walking.

Kava-containing products have been associated with liver-related injuries
including hepatitis, cirrhosis, and liver failure The presence of kava
in a supplement should be identified on the product label in the "Supplement
Facts" box. The following are commonly used names for kava:

ava
ava pepper
awa
intoxicating pepper
kava
kava kava
kava pepper
kava root
kava-kava
kawa
kawa kawa
kawa-kawa
kew
Piper methysticum
Piper methysticum Forst.f.
Piper methysticum G. Forst.
rauschpfeffer
sakau
tonga
wurzelstock
yangona

PC SPES, SPES (BotanicLab)
Audience: Urologists, Consumers
Consumers are warned to stop using the dietary supplement / herbal products
PC SPES and SPES capsules because they contain undeclared prescription drug
ingredients that could cause serious health effects if not taken under
medical supervision. Laboratory analysis of the products by the California
Department of Health Services found PC SPES contains warfarin and SPES
contains alprazolam, which are available only by prescription and sold either
by their generic names or the trade names, Coumadin and Xanax. PC SPES and
SPES are respectively marketed "for prostate health" and strengthening the
immune system. BotanicLab, the manufacturer of the products, has voluntarily
recalled PC SPES and SPES nationwide.
FDA Concerned About Botanical Products, Including Dietary Supplements,
Containing Aristolochic Acid

The agency has issued a Consumer Advisory and sent updated letters to
industry and health professionals to communicate our concern about the use
and marketing of dietary supplements or other botanical-containing products
that may contain aristolochic acid. The use of products containing
aristolochic acid, including botanical products marketed as traditional
medicines, has been associated with nephropathy. Because of our concerns
about botanical-containing products known or suspected to contain
aristolochic acid, we will be pursuing appropriate regulatory action
regarding these products.

FDA ISSUES A NATIONWIDE ALERT ON THE RECALL OF THIRTEEN "TREASURE OF THE EAST" HERBAL PRODUCTS BECAUSE OF POSSIBLE HEALTH RISK
The FDA is warning consumers to discontinue use of thirteen Chinese herbal
products containing aristolochic acid because they may present a serious
health hazard to consumers. Aristolochic acid found in certain plants and
botanicals is toxic to the kidneys and is a potent carcinogen. The use of
aristolochic acid containing products has been linked to increased risk of
kidney cancer in people who have consumed it.
The use of comfrey in dietary supplements is a serious concern to FDA. These
plants contain pyrrolizidine alkaloids, substances which are firmly
established to be hepatotoxins in animals. Reports in the scientific
literature clearly associate oral exposure of comfrey and pyrrolizidine
alkaloids with the occurrence of veno-occlusive disease (VOD) in animals.
Moreover, outbreaks of hepatic VOD have been reported in other countries over
the years and the toxicity of these substances in humans is generally
accepted. The use of products containing comfrey has also been implicated in
serious adverse incidents over the years in the United States and elsewhere

The Food and Drug Administration is warning consumers not to purchase or
consume Nature's Nutrition Formula One products labeled as containing Ma huang
(ephedrine) and kola nut because the product poses a risk to consumers'
health. The products are sold by Alliance U.S.A. of Richardson, Texas. \
FDA has determined that the products can cause severe injury or death in some
people who consume them. Nature's Nutrition Formula One is labeled as a
dietarysupplement and has been marketed with labeling purporting that itis
useful for weight loss and energy enhancement FDA has been receiving
increasing numbers of reports recently of adverse events associated with the
use of certain products marketed as dietary supplements for weight loss,
energy, and ergogenic (performance-enhancing) and body-building purposes.
These apparently diverse categories of products often contain a number of
similar ingredients, including Ma huang (Ephedra sinica or Chinese ephedra, a
botanical source of ephedrine, pseudoephedrine, and norpseudoephedrine),
guarana or Kola nut (caffeine sources), white willow (salicin source), and
chromium. They may also contain various amino acids, glandular products, or
other nutrients. They are touted for their reported stimulant effects (pep or
energy) and their ability to enhance metabolism with subsequent weight loss
(so-called "fat burners").
The Food and Drug Administration (FDA) is warning consumers to immediately
stop use of the product LipoKinetix®, marketed as a dietary supplement by
Syntrax Innovations, Inc. LipoKinetix has been implicated in a number of
serious liver injuries. FDA has received multiple reports of persons who
developed liver injury or liver failure while using LipoKinetix.
LipoKinetix is marketed for weight loss. It contains the ingredients
norephedrine (also known as phenylpropanolamine or PPA), caffeine, yohimbine,
diiodothyronine, and sodium usniate.

The Food and Drug Administration is again warning consumers of products
marketed as dietary supplements that contain tiratricol, also known as
triiodothyroacetic acid or TRIAC, a potent thyroid hormone that may cause
serious health consequences including heart attacks and strokes

glucosamine or chondroitin. The most common side effects are increased
intestinal gas and softened stools. However, animal research has raised the
possibility that glucosamine may worsen insulin resistance, a major cause of
diabetes. So far, studies in humans have not substantiated that risk.
Nevertheless, people with diabetes should monitor their blood-sugar level
particularly carefully when using that supplement. There have been no reports
of allergic reactions to glucosamine. But since it's made from shellfish
shells, people who are allergic to seafood should use it cautiously, watching
for reactions, or avoid it entirely. As for chondroitin, it can cause
bleeding in people who have a bleeding disorder or take a blood-thinning drug.