Research Article: An increase in ALS incidence on the Kii Peninsula, 1960-2009: A possible link to change in drinking water source

Date Published: May 28, 2012

Publisher: Informa Healthcare

Author(s): Tameko Kihira, Sohei Yoshida, Tetsuya Kondo, Keiko Iwai, Sachiko Wada, Satomi Morinaga, Yoshinori Kazimoto, Tomoyoshi Kondo, Kazusi Okamoto, Yasumasa Kokubo, Shigeki Kuzuhara.


We investigated changes in the incidence of amyotrophic lateral sclerosis (ALS) in the Koza/Kozagawa/Kushimoto area (K. area) in the Kii Peninsula, Japan in 1960–2009. Probable and definite ALS cases diagnosed using El Escorial criteria were collected during a five-decade period: period I-V, 1960–2009. Forty-three ALS patients matched the selection criteria in the overall K. area, including three patients on Oshima, a small island opposite the mainland K. area. The age- and gender-adjusted incidence of ALS in the overall K. area (standardized for the 2005 Japanese population) decreased from 5.47/100,000 (95% CI 1.86–9.08) in period I to 0.61/100,000 (95% CI-0.28–1.50) in period III, and then increased to 4.39/100,000 (95% CI 1.70–7.07) in periodV. On Oshima, the age- and gender-adjusted incidence of ALS was 9.45/100,000 (95% CI—7.39–26.29) in period V. The present research indicates an increase of ALS incidence in the K. area, especially on Oshima. A limitation of this study was the small population.

Partial Text

Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset degenerating disease of unknown etiology of the motor neuron systems. The Koza, Kozagawa and Kushimoto (K.) area in the Kii Peninsula of Japan was reported to have a higher incidence of ALS in the 1950s than other areas of the world (1–5). Epidemio-logic research showed that drinking water sourced from Kozagawa River in the K. area contained severely low levels of Ca and Mg, and Ca/Mg deficiency was speculated to have a role in the development of ALS in these areas (5,6). On Oshima, a small island municipally included in the K. area, the source of drinking water was changed from regional water to the Kozagawa River in 1975. To clarify whether ALS epidemiology on Oshima changed after altering the water source, we investigated changes in ALS incidence on Oshima and in the K. area in 1960–2009.

The age- and gender-adjusted ALS incidence in the K. area decreased from 5.47 in 1960–1969 to 0.61 in 1980–1989, and then increased to 4.39 in 2000–2009. The declining trend of the male: female ratio in the past 10 years was comparable with other reports (9,10), and the recent increase of ALS incidence in females could be related to some type of environmental or cultural factor pertaining in females in this area and the increased confirmation of older female patients (11). The reason for the decline in 1980-1989 is not clear, but might be partially due to missing cases from the data set, emigration, and environmental, lifestyle and cultural changes. Recent reports of annual age-adjusted ALS incidences ranged from 0.42/100,000 (12) to 2.96/100,000 (13) in other areas in the world (14–17). Taken together, the age-and gender-adjusted incidence in the K. area and Oshima in 2000-2009 was higher than in other areas. On Oshima, no patient with ALS was found in previous research in 1946–1965 (18). It is noteworthy that a high ALS incidence was first found on Oshima in 2000–2009 after the drinking water source was changed to the Kozagawa River in 1975. The present research indicated an increase of ALS incidence in the K. area, especially on Oshima. A limitation of this study was the small population. Continuous study over a longer period is needed in this area.