Discussion
Chronic arsenic toxicity may cause peripheral neuropathies, parasthesia, ataxia, cognitive deficits, fatigue, and muscular weakness. GI complaints include anorexia, hepatomegaly, jaundice, nausea, and vomiting. Skin afflictions may include erythema, eczema, pigmentation (arsenic melanosis), diffuse alopecia, keratosis (especially of palms and soles), scaling and desquamation, brittle nails, white lines or bands in the nails (Mees lines), and localized subcutaneous edema. White striae in the fingernails are consistent with a diagnosis of arsenical polyneuritis, even though urine and hair arsenic concentrations may be within normal limits (Heyman et al. 1956).
Manifestations of chronic arsenic ingestion depend on both the intensity and duration of exposure. Our case had a more severe presentation than would be expected with an elevated urinary arsenic concentration of 83.6 µg/g creatinine. The intensity of her symptoms may have been the result of her lengthy duration of exposure or perhaps of an undiagnosed underlying condition. Also, that a single spot urine may not be as accurate as a 24-hr urine sample, despite adjustment for creatinine concentration.
In most cases the toxic moiety is presumably trivalent arsenic in the form of inorganic arsenious acid (arsenite), or an organic arsenoxide, rather than the element itself. Pentavalent arsenicals may be reduced, to a small extent in vivo, to the active trivalent form. This in vivo conversion may explain why all chemical forms of arsenic eventually produce the same toxic syndrome.
Elemental arsenic is found naturally in the earth's crust at concentrations of 2-5 ppm (Tamaki and Frankenberger 1992). Arsenic is released into the environment through both natural sources (i.e., soil erosion, volcanoes) as well as anthropogenic sources (e.g., release from metal mining and smelting, pesticide application, coal combustion, waste incineration). Most arsenic release into the environment is inorganic and accumulates by binding to organic soil matter (Smedley and Kinniburgh 2005).
Soils with high arsenic concentrations can yield foods with exceedingly elevated arsenic levels. Diet is the largest source of exposure for nonoccupationally exposed individuals, with an average total (inorganic and methylated) arsenic intake of 40 µg/day. U.S. dietary intake of inorganic arsenic has been estimated to range from 1 to 20 µg/day (Schoof et al. 1999). Because of high arsenic concentration in algae and marine microorganisms, seafood is the highest dietary source of arsenic (Tao and Bolger 1999). Arsenic concentrations for fish and seafood average 4-5 ppm (Bennett 1981), significantly higher than concentrations found in grains and cereals, with an average of 0.02 ppm (Gartrell et al. 1986). Although chronic low-level exposure to arsenic does occur from dietary sources, it is usually significantly below toxic levels. The tragedy of acute and chronic arsenic poisoning from contamination of water in Bangladesh, West Bengal, and elsewhere in the world has recently been described (Mead 2005).
A number of published studies have highlighted cases in which homeopathic remedies cause clinical arsenic toxicity. One such study describes 74 patients in Singapore who were victims of chronic arsenic poisoning caused by local antiasthmatic herbal preparations (Tay and Seah 1975). Systemic involvement mainly affected the patients' skin (hyperpigmentation, hyperkeratosis), nervous system (polyneuropathy, tremors, headache), and GI system (gastroenteritis, toxic hepatitis). Of the 74 patients studied, 10 presented with malignancies. Of the 29 herbal preparations analyzed in this study, 16 contained inorganic arsenic in concentrations of 25-1,000 ppm, and 10 contained 1,001-50,000 ppm.
Mitchell-Heggs et al. (1990) reported on a 33-year-old Korean woman who presented with malaise, difficulty walking, arthralgia, and diarrhea. Her elevated urine and blood arsenic levels were linked to an herbal treatment for hemorrhoids, which contained 10,000 ppm arsenic. The patient recovered completely after ceasing her usual dosage of 90 pills/day (50 mg/day).
Espinoza et al. (1995) analyzed traditional Chinese herbal balls, which are taken for a variety of conditions, including rheumatism and cataracts. The herbal balls were found to contain up to 36.6 mg arsenic per ball. The authors concluded that with a "recommended dose" of two herbal balls daily, the preparation "poses a potentially serious health risk to consumers." They advised that "health professionals should be aware that patients who consume traditional Chinese remedies may be exposed to potentially toxic substances" (Espinoza et al. 1995).
To our knowledge, only one case study has previously documented arsenic toxicity related to consumption of herbal kelp supplements. Walkiw and Douglas (1975) reported on two patients admitted for neurologic investigation with elevated urinary arsenic excretion (138 and 293 µg/24 hr). Through detailed history and laboratory sampling, both cases were linked to ingestion of kelp supplement. Urinary arsenic concentrations declined to normal range (< 10 µg/24 hr) within 3 months of discontinuing kelp supplements. The initial presenting signs of foot-drop also resolved.
To assess the concentration of arsenic present in commercially available kelp supplements, we purchased nine over-the-counter kelp samples from local health food outlets. Included were samples from three different batches of the product that was consumed by the patient. We determined total arsenic in the herbal samples by inductively coupled argon plasma (ICP) using the identical hydride vapor generation method, as described by Tracy et al. (1991). The ICP used was an Applied Research Laboratories-model Accuris, and fitted with a Noordermeer V-groove nebulizer (both from Fisons Instruments, Valencia, CA). All samples were analyzed randomly in a blindfolded manner.
Laboratory analysis by the California Animal Health & Food Safety Laboratory found detectable levels of arsenic in eight of the nine kelp herbal supplements, ranging from 1.59 ppm to 65.5 ppm by dry weight (1.59, 2.28, 9.55, 9.97, 10.5, 24.1, 34.8, and 65.5 ppm); the median value was 10.23 ppm. One of the nine samples was below the method detection limit of 0.010 ppm. The three samples of the brand of kelp supplement consumed by our patient throughout the duration of her symptoms showed arsenic concentrations of 34.8, 2.28, and 1.59 ppm.
In a recent analysis of ayurvedic herbal medicine products, Saper et al. (2004) found that 20% of products tested contained heavy metals. Detectable arsenic levels in 6 of 70 samples ranged in concentrations from 37 ppm to 8,130 ppm. Although the kelp samples we analyzed were consistently elevated, the concentration of arsenic in our samples was considerably lower than previously documented concentrations in herbal remedies (Mitchell-Heggs et al. 1990; Saper et al. 2004; Tay and Seah 1975). This raises the concern that chronic exposure to contaminated supplements, even with moderately elevated arsenic concentrations, could still be toxic. None of the supplements contained labeling information regarding the possibility of contamination with arsenic or other heavy metals.
The Food and Drug Administration (FDA) has set tolerance levels for arsenic in certain food products. These permissible levels range from 0.5 ppm in eggs and uncooked edible tissues of chickens and turkeys to 2 ppm in certain uncooked edible by-products of swine. The concentration of arsenic found in seven of the nine supplements exceeded the FDA tolerance level of 2 ppm (Agency for Toxic Substances and Disease Registry 2006).
In 1998, the California Department of Health reported that 32% of traditional Asian medicines sold in the state contained heavy metals (including lead, mercury, and arsenic) or undeclared pharmaceuticals (Ko 1998). Although this case report focuses on the potential for arsenic contamination in herbal supplements, lead exposure from supplements is also of increasing concern (Mattos 2006). Labeling information provides little warning; two-thirds of homeopathic medicines sampled contained arsenic levels higher than indicated on the label (Kerr and Saryan 1986).
The popularity of herbal treatments and dietary supplements has increased at an astonishing rate. In 2001, $178 billion was spent in the United States on dietary supplements (Anonymous 2002). Of the many reasons for the increasing popularity of supplements, the most important has been attributed to the enactment of the Dietary Supplement and Health Education Act (DSHEA 1994; Marcus and Grollman 2002). DSHEA amends the Food and Drug Act (1938) to define the way dietary supplements are regulated and labeled. Under DSHEA (1994), herbal, vitamin, and mineral treatments are considered dietary supplements, and the act limits the FDA's control over substances classified as dietary supplements.
Commenting on DSHEA, former FDA commissioner David A. Kessler stated that
[T]he Act does not require that dietary supplements be shown to be safe or effective before they are marketed. The FDA does not scrutinize a dietary supplement before it enters the marketplace. (Kessler 2000)
Instead, Kessler noted, the FDA must rely on adverse event reports to determine product safety and efficaciousness. As a result, dietary supplements such as herbal therapies are now subject to lower safety standards than food additives. In a review of regulations for botanical medicines, Mitchell-Heggs et al. (1990) warned that
Consumers are provided with more information about the composition and nutritional value of a loaf of bread than about the ingredients and potential hazards of botanical medicines.
Environ Health Perspect. 2007;115(4):606 © 2007 National Institute of Environmental Health Sciences
Cite this: Case Report: Potential Arsenic Toxicosis Secondary to Herbal Kelp Supplement - Medscape - Apr 01, 2007.
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