Herbs have been used worldwide as complementary and alternative medicines (CAMs) for thousands of years. Korea has traditionally used a variety of herbal products, and 85.5% of the Korean general population has used an herbal medicine more than once in their lifetime1. Herbs are cultivated and harvested in natural environments and, thus, are heavily influenced by metal contamination of the soil and surrounding environment. Therefore, many countries consistently analyze the metal contents of herbs and herbal products2345.

In Korea, herbs are categorized as ‘food ingredients’ when used as foodstuffs and ‘herbal plants’ when used for medicinal purposes. Herbal plants used by Korean herbal doctors, the Hospital of Oriental Medicine, pharmaceutical companies, pharmacies, and Oriental medicine dispensaries should meet quality-control standards based on the regulations of the Korea Food and Drug Administration (KFDA)6789. However, the updated Korean herb and herbal-product purity guidelines include only four heavy metals, arsenic (As), lead (Pd), cadmium (Cd), and mercury (Hg), whereas other metals are measured as the sum of the total metals using the sulfide precipitation method.

In Korea, 43.6% of adverse reactions associated with Oriental medicines involve dermatological problems, which are the most common side effects1. For example, contact dermatitis, arsenic keratosis, phototoxicity, and alopecia have been reported after using herbal products10. Since the 2000s, countries around the world have noted that CAMs, including herbs, may be an important ingestion factor for metal antigens such as nickel, chromium, cobalt, and mercury11121314. However, no studies have investigated the metal contents of Korean herbs and herbal products with the potential to cause contact dermatitis. Therefore, this study aimed to identify the metal contents of Korean herbs and herbal products and to give information on counselling metal allergic patient compared with previous reports in literature reviews.

The results from the quantitative analyses of 30 herbal items, including herbal plants, herbal products, and herbal extracts, are shown in Table 2.

As CAM use broadens worldwide, and the international market expands rapidly, emphasis on the safety and quality of herbs and herbal products is increasing17. According to the World Health Organization (WHO), herbal products were regulated in 65 countries in 1999 but in as many as 119 in 201218.

In Korea, various herbal products are used in medical institutions such as the oriental medicine hospitals, pharmacies, as well as in the private sector in functional foods, teas, and spices. The regulation of heavy metals in herbal products was strengthened in April 2006 in Korea, and the limits of four metals (Pb ≤5 ppm, As ≤3 ppm, Cd ≤0.3 ppm, and Hg ≤0.2 ppm) were incorporated into previous regulations recommending total amounts ≤30 ppm. Because most final herbal extracts and products prescribed by Korean herbal doctors consist of several raw herbal plant materials, herbal extracts and products may have metal levels several times higher than each herbal plant components. In this study, ingesting some herbal extract led to daily metal intake values up to 22.63 times higher Co and up to more than five thousand times higher Ni than for ingesting an herbal plant (Table 2). However, herbal plants and specific herbal products listed in the KFDA are regulated in Korea, whereas herbal products prescribed by Korean herbal doctors are not. Same regulation limit applies to herbal plants, which are raw materials, and herbal products, the final products. In contrast to the Korean Pharmacopoeia (KP), Canada and USA apply stricter regulations to final products than raw materials19. Although the regulations on herbal products have been strengthened, these regulations refer only to certain heavy metals, and there have been no standards for evaluating metals as allergens until now.

Fortunately, most of the herbal plants and products analyzed in this study had little metals relative to permissible tolerable daily intake levels provided by several international organizations (Table 3).

Ni is a ubiquitous element with strong antigenicity, and Ni allergies are generally reported in 10% to 20% of the population. Food and water are the primary sources of Ni exposure. The level of dietary Ni intake varies from 20 to 600 µg/d, depending on the geographic area152021. A strong correlation has been observed between the amount of ingested Ni and allergic contact dermatitis. Dietary interventions, including Ni restriction, are important for treatment and prevention of Ni allergy, because very low concentrations (10~60 µg/kg) can elicit allergic reaction after sensitization 202223. Well-known Ni-rich foods include cocoa, peanuts, and chocolate. Jacob et al.24 reported that four Ni allergic children who improved after strict Ni restriction diet showed abrupt deterioration after eating chocolate bars, and Krecisz et al.14 reported a case of systemic contact dermatitis following cocoa ingestion232425. In these two reports, Ni in the food was approximately 50 µg (50 g/chocolate bar, 1.00 [0.85~1.32] mg/kg Ni24; 5 g/recommended daily dose of cocoa powder, 10 mg/kg Ni26).

In this study, six herbal extracts had daily Ni intake similar to or higher than 50 µg (Table 2). Han et al.25 analyzed Ni content of Korean foods in 2005 and found considerably more Ni in most Korean foods than previous reports. For example, the Ni content of Korean green tea bags is 7,852 times higher than that reported by Veien and Andersen26 in 198625. Fortunately, the Ni contents of herbal plants and products in this study were considerably lower than those previous reported from other countries 2327293031. However, the metal contents of herbal plants and products can differ greatly, even in the same country, depending on types of selected herbal plants, cultivation environment, and time obtained 229. Thus, interpretations of these results should be careful 232728293031.

Cr is commonly used in alloys and showed sensitization rate up to 6%32. Irritant dermatitis, dyshidrotic eczema, and contact dermatitis are closely related to dietary or medicinal Cr. Fregert and Rorsman33 reported that a provocation test using 50 µg oral dichromate salt in five Cr allergy patients caused acute flare-ups of hand eczema. Korean herbal products contain average Cr of 0.618 ppm, which is six times higher than daily diet (0.1 ppm)34. In this study, six herbal plants and one herbal product contained five times more Cr than nuts (0.7 ppm), a wellknown Cr-rich food35. One herbal plants, Herb G (prepared Rehmannia root) contained 3.685 ppm (Table 2).

Co exposure commonly occurs via inhalation, oral ingestion, and contact and can cause irritant dermatitis, contact dermatitis, allergic vasculitis, and hand eczema (dyshidrotic eczema)36. Like Ni, geographic and environmental conditions affect Co contents of food and water37. Stuckert and Nedorost36 suggested that <12 µg/d is appropriate for standard Co-restricted diet. In this study, four herbal extracts had Co levels higher than 50% of the restricted diet standard, and one (Herbal extract G, 7.13 µg/d) had up to 60% (Table 2).

In Korea, many patients use CAMs to treat allergic diseases such as asthma, rhinitis, atopic dermatitis, and urticaria1. But significant levels of high-antigenicity metals, such as Ni, Co and Cr are contained in Korean herbal plants and products compared with the metal levels in Nior Cr-rich foods which can aggravate metal allergy patient or those of Co-restricted diets.

In addition to the metals assessed in this study, other studies have reported that CAMs contain manganese, iron, zinc, and selenium. Assessments of these metals in Korean herbal products should be conducted in the future430.

When describing metal-restricted diets, most authors distinguish between metal-rich and low-metal foods based only on metal content. However, in addition to content, actual dietary intake amount is an important factor for metal exposure. Dietary intake should be taken into consideration in dietary education. In this study, the lowest mean metal content was detected in herbal extracts compared with herbal plants and products sold in Korean drugstores. However, when the contents were converted to daily intake values, there was 5.15 times higher in Co and 8.32 times higher in Ni daily metal intake from herbal extracts than from herbal plants.

The present study is limited in that it involved a small sample number and purchased only in Seoul. Furthermore, because all of the samples were KFDA-approved, these results do not represent the herbs obtained from markets.

In previous analyses of Korean herbs, only certain heavy metals (Pb, As, Cd, and Hg) in raw herbal plant were assessed. Therefore, this study was the first to analyze metal antigens in Korean herbal plants and the final ingested forms of herbal products. The herbal preparations contained similar or higher metal than known metal-rich foods. The KFDA has strict regulations on heavy metals, pesticide, and aflatoxins but does not provide standards for metal antigens. The allergenicities of herbal products have been underestimated. Metal exposure differs depending on the intake amount, and place of purchase, even for the same herb. Therefore, doctors should perform a detailed medical history about the usage of herbal products and the place of purchase for patients with intractable contact dermatitis or acute deteriorated lesions.