42 Current Aging Science, 2011, 42-56 A High Accumulation of … · 2017-05-31 · A High Accumulation of Hair Minerals in Mongolian People Current Aging Science, 2011, Vol. 4, No

42 Current Aging Science, 2011, 4, 42-56

1874-6098/11 $58.00+.00 © 2011 Bentham Science Publishers Ltd.

A High Accumulation of Hair Minerals in Mongolian People: 2nd

Report; Influence of Manganese, Iron, Lead, Cadmium and Aluminum to Oxida-tive Stress, Parkinsonism and Arthritis

Fumio Komatsu1,*, Yasuo Kagawa

1, Terue Kawabata

1, Yoshinori Kaneko

1, Ulziiburen Chimedreg-

zen2, Baatar Purvee

3 and Jugder Otgon

4

1Kagawa Nutrition University, 3-9-21 Chiyoda, Sakado, Saitama, 350-0288, Japan,

2Mongolian Medical Women’s As-

sociation, Ulaanbaatar, Mongolia, 3Citizens Representative Convention in Huvsgul Prevince, Mongolia,

4Huvsgul Prov-

ince Hospital, Murun City, Huvsgul Province, Mongolia

Abstract: It was previously reported that the hair of Mongolian people showed very high accumulation of manganese

(Mn), which may increase oxidative stress. This study (2nd

report), indicated that not only Mn but other minerals had also

accumulated at high levels in hair. It describes the influence of these minerals on oxidative stress, Parkinson’s disease-like

symptom (Parkinsonism) and arthritis, these diseases being prevalent in Mongolia. Methods: 299 subjects were enrolled

(including 21; Parkinsonism and 25; arthritis) from Ulaanbaatar and 5 other areas in Mongolia. Oxidative stress was

evaluated by measuring the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). The minerals accumulated in scalp

hair were measured by the inductively coupled plasma mass spectrometry method. As a control, 81 healthy Japanese sub-

jects were enrolled. Results: Mongolian subjects showed high accumulated levels of Mn, iron, lead, cadmium and alumi-

num accumulations in hair, as compared with Japanese subjects. These levels were correlated with urinary 8-OHdG lev-

els. The subjects with Parkinsonism and arthritis demonstrated higher levels in these minerals than healthy subjects. Con-

clusion: High accumulations of these minerals may increase oxidative stress in Mongolian people, and induce Parkin-

sonism and arthritis through the high oxidative stress. The high accumulations of these minerals may be induced by eating

large amounts of sheep meat. In addition, sandy wind pollution may also contribute to it.

Keywords: Mongolians, oxidative stress, manganese, lead, cadmium, parkinsonism, arthritis.

INTRODUCTION

Mongolia is located in the center of the Eurasian Conti-nent and has an extremely severe climate. The temperature reaches 35°C in summer and drops lower than -40°C in win-ter. Rain fall is scarce. Although there are large green fields, twenty percent of the territory is dry land. Sandy wind blows from the western areas. The population is 2,590,000. Life expectancy at birth, 64 years for males and 69 years for fe-males (Health Indicators, 2008, the Ministry of Health, Mongolia), is relatively short compared to that for the Japa-nese, being 79 years for males and 86 years for females (Sta-tistics and Information, 2008, the Ministry of Health, Labor and Welfare of Japan). Mongolians and Japanese belong to the same ethnic group of Neo-Mongoloid people, which are different from Paleo-Mongoloid people such as America Indians and Pacific Ocean aborigines [1,2]. Thus, such com-parison may be meaningful in understanding the health status of Mongolian people. Thirty-three percent of Mongolians are under 15 years. Elderly people over 65 make up less than 5% of the population (22% in the Japanese population). The low percentage of elderly people indicates a shorter life span.

As previously reported, Mongolian people were exposed to high oxidative stress, which may relate to early aging [3,4]. Such high oxidative stress may be induced by many

*Address correspondence to this author at the Kagawa Nutrition University,

3-9-21 Chiyoda, Sakado, Saitama 350-0288, Japan; Tel/ Fax: +81-49-282-

3702; E-mail: [email protected]

factors, including the severe climate, strenuous labor, long time ultraviolet exposure, heavy smoking and in particular, the insufficiency of anti-oxidant food such as vegetables and fruit. However, oxidative stress in Mongolians was very high as compared with that of the Japanese. So a further contrib-uting factor was speculated. In 2008, hair minerals in Mon-golian people were assayed and found to show a very high accumulation of manganese (Mn) [5]. This high Mn accumu-lation was considered inductive to high oxidative stress be-cause it was significantly correlated with oxidative stress markers such as serum malondialdehyde-modified low-density lipoprotein (MDA-LDL), serum reactive oxygen metabolites (ROM) by a d-ROM test (Diacron, Gresseto, Italy) and urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels.

In 2008, a hair mineral assessment was performed at Mu-run city in the northern area of Mongolia. In 2009, the as-sessment was extended from south-east Gobisumber to north-west Tsagan-uul, covering 1,300 km through central Mongolia. It found that not only Mn, but iron (Fe), lead (Pb), cadmium (Cd), aluminum (Al) and several other minerals were accumulated at high levels in people. It is known that the excessive accumulation of harmful minerals in the body increases oxidative stress [6,7], and leads to several nervous disorders and inflammatory diseases [8,9]. In Mongolia, Parkinson’s disease-like symptoms (Parkinsonism) and ar-thritis, including rheumatoid arthritis, spondylitis, osteoar-thritis of the spine and degenerative joint disease, are preva-

A High Accumulation of Hair Minerals in Mongolian People Current Aging Science, 2011, Vol. 4, No. 1 43

lent. Although these diseases are caused by different mecha-nisms, high oxidative stress may trigger them [10-13]. Thus, this report describe the relationship of these diseases and oxidative stress with the high accumulation of minerals in Mongolian people. Furthermore, the routes by which these minerals have entered the body are also discussed.

METHODS

Investigated Places

This investigation was performed in summer, 2009, in the capital, Ulaanbaatar, and in five country areas, Gobisum-ber, Erdenet, Murun, Aleg-erden and Tsagan-uul (Fig. 1). Ulaanbaatar has a population of 1,250,000, with roads filled with vehicles, thick dust and vehicular exhaust. Gobisumber is a small town, population 3,000, 400 km from Ulaanbaatar in the south-east, near the Gobi desert. The land is dry, with dusty wind from the western area. There is a coal mining factory 30 km from town where the inhabitants work. This investigation was performed in the clinic which takes care of health. Erdenet is a big city, population 90,000, 460 km from Ulaanbaatar in the north-western area. It has a large copper (Cu) and molybdenum (Mo) mining factory which people depend on. Murun, Aleg-erden and Tsagan-uul are all in Huvsgul Province, the coldest district in this country. The air is clean, but dusty wind often blows across this province. People breed sheep, cattle, goats, horses, camels and rein-deer. Murun is a city 770 km from Ulaanbaatar, with a popu-lation of 38,000. Aleg-erden and Tsagan-uul are small vil-lages of about five hundred people. Aleg-erden is situated 65 km north of Murun, and Tsagan-uul is 180 km north-east of Murun, near the Russian federation.

Subjects

The number of subjects are shown in Table 1. From the countryside of Gobisumber, Erdenet, Murun, Aleg-elden and Tsagan-uul, a total of 244 subjects were randomly enrolled (including 214 healthy subjects, 10 with Parkinsonism and 20 with arthritis), ranging in age from 10 to 82 years (mean age±SD: 39.7±13.4 y-o). Parkinsonism was diagnosed through symptoms including hand tremor, difficulty in walk-ing, muscle rigidity, and several extra-pyramidal signs. Rheumatoid arthritis, spondylitis, osteoarthritis of the spine and degenerative joint disease were diagnosed by arthralgia, lumbago, back pain, and some clinical examinations. All subjects were living in small houses or gers. Healthy subjects looked to be sufficiently nourished and worked outdoors every day. No healthy subjects routinely took supplements. As well, 55 subjects in Ulaanbaatar were enrolled, (including 39 healthy subjects, 11 with Parkinsonism and 5 with arthri-tis). The healthy subjects of Ulaanbaatar were divided into two groups, one being indoor workers such as medical doc-tors, nurses, dentists, school teachers and public officers, the other being outdoor workers from road construction, house building, truck-driving and street stall. The subjects with Parkinsonism and arthritis in Ulaanbaatar had been treated by family clinics. As a comparison, 81 healthy Japanese sub-jects from the Tokyo area were randomly enrolled. The pro-tocol for this study was approved by the Ethics Committee of the Kagawa Nutrition University (No 53 and No 54). The subjects gave written informed consents before the study.

Measurement of Hair Minerals

To know the accumulation level of minerals in the body, scalp hair (about 0.2g) was collected from the subjects, and

Fig. (1). Investigated places in Mongolia and Japan. There is a distance of 1,300 km from Gobisumber to Tsagan-uul.

44 Current Aging Science, 2011, Vol. 4, No. 1 Komatsu et al.

hair minerals (including many metals, some semi-metals and non-metals) were measured. The measurement was per-formed by a research laboratory (La Belle Vie Inc. Tokyo, Japan), in accordance with the procedures recommended by the Hair Analysis Standardization Board [14]. In brief, a hair sample of 75 mg was weighed into a 50 ml plastic tube, and washed twice with acetone, then with 0.01% Triton solution. Thus, hair coloring, oil and dust were removed. The washed hair sample was mixed with 10 ml of 6.25% tetramethylam-monium hydroxide (Tama Chemical, Tokyo, Japan) and 50μl of 0.1% gold solution (SPEX Certif. Prep. Tokyo, Japan), and then dissolved at 75°C by shaking for 2 hours. After cooling the solution to room temperature and adjusting its volume gravimetric, the obtained solution was measured by using the inductively coupled plasma mass spectrometry method (ICP-MS; Agilent-7500i and 7500c). The results were expressed as ng/g hair (ppb) or μg/g hair (ppm). Accu-mulated levels were compared with those of Japanese sub-jects and Japanese standards. Japanese subjects were en-rolled as a control in this study, as described above. Japanese standards were established by a laboratory (La Belle Vie Inc.) from the determinations of 6,000 healthy Japanese peo-ple [15].

Evaluation of Oxidative Stress

To evaluate oxidative stress in this study, the level of urinary 8-OHdG alone was measured, because it had previ-ously been established that urinary 8-OHdG levels were sig-nificantly correlated with the levels of serum MDA-LDL and serum ROM (d-ROM test) [5,16]. Urine samples were ob-tained from the subjects and rapidly frozen, sent to Tokyo and stored at -80°C until analysis. The analysis was per-formed by an enzyme-linked immunosorbent assay in a re-search laboratory (Japan Institute for Control of Aging, Si-zuoka, Japan).

Measurement of Minerals Contained in Drinking Water, Meat, Wild Grasses and Soil

The amount of minerals contained in drinking water, sheep meat, wild grasses and soil in Mongolia was also measured and compared with results from Japanese samples. Drinking water samples were obtained from well water in the investigated places. Grasses and Mongolian sheep meat were obtained in Murun. As a control, Japanese cattle meat was used. Samples were heated for 16 hours at 550°C. The ash was dissolved in a hydrochloric acid (HCl)-water solu-tion and dried on a boiled water bath, then dissolved again in

Table 1. Number of Subjects

Mongolian Subjects

Males Females Age

M ± SD

Countryside 244 111 133 39.7 ± 13.4

Gobisumber 54 30 24 38.4 ± 12.9

Erdenet 51 25 26 38.5 ± 11.7

Murun 73 27 46 42.1 ± 14.7

Aleg-erden 55 26 29 36.1 ± 15.2

Tsagan-uul 11 3 8 58.9 ± 12.8

Healthy subjects) 214 94 120 38.9 ± (13.6)

Parkinsonism) 10 5 5 55.1 ± (9.3)

Arthritis) 20 12 8 47.1 ± (9.8)

Ulaanbaatar 55 21 34 47.3 ± 14.8

Healthy subjects)

(Indoor workers) 15 4 11 44.2 ± (11.3)

(Outdoor workers) 24 16 8 42.7 ± (10.5)

Parkinsonism) 11 1 10 57.3 ± (10.2)

Arthritis) 5 0 5 48.8 ± (8.3)

Japanese subjects (Control)

Tokyo area 81 40 41 45.7 ± 14.2

(Healthy subjects)


a HCl-water solution and heated for 10 min on the boiled water bath, then filtrated. Finally, the sample concentration was adjusted with water. Soil samples were obtained from the surface soil of the residential land of the subjects. After these samples were dissolved with distilled water (pH : 7.30, 23°C), pH was measured using the top clear layer. The soil samples were dissolved using nitric acid (HNO3), and the minerals were extracted and diluted in HNO3-water. The quantities of specific content in the samples were measured using an ICP-MS.

Statistical Analysis

The results were expressed as a mean average and stan-dard deviation (M±SD). For evaluation of the difference, a Student’s t-test was used, and a p value <0.05 was consid-ered to be statistically significant.

RESULTS

1. Measurements of Hair Minerals

(1) The level of hair mineral accumulation in 214 country-side healthy subjects from Gobisumber, Erdenet, Murun, Aleg-erden and Tsagan-uul, was measured and com-pared with that of Japanese subjects (Japanese standards and Japanese healthy subjects). Healthy subjects in Ulaanbaatar showed different tendencies between indoor and outdoor workers. Thus, these results were not in-cluded in this calculation (the results are described later). As shown in Table 2, accumulated levels of the countryside subjects were different according to which minerals. In particular, very high levels in Mn, Fe, Cd, Pb and Al were shown, with low levels of mercury (Hg) and selenium (Se) accumulations. Sodium, potassium, magnesium, chromium (Cr), cobalt (Co), lithium (Li) and Mo also showed high levels, and Cu demonstrated relative low level. In this study, excepting children, most were smokers and drinkers, so there were not divided. Because it is known that Mn, Fe, Cd, Pb and Al enhance oxidative stress, it is mostly these minerals that were mentioned in the following descriptions.

(2) Hair mineral accumulations of countryside healthy male and female subjects were compared. As shown in Table

3, Fe, Cd, Pb and Al levels were significantly higher in males than in females, whereas the Mn level was higher in females than in males, although no significantly.

(3) The levels of minerals among the investigated places were compared. As shown in Table 4, there were some differences. Mn, Fe, Pb, Cd and Al levels were rela-tively high in Gobisumber. Se and Hg levels were low in all investigated places. The Se level decreased going northward, and was lowest in Tsagan-uul.

(4) The relationship of mineral accumulation to age was investigated. As shown in Fig. (2), no correlation be-tween these levels and ages was observed. High accu-mulations were observed even in 10-19 year olds.

(5) The relationship of Mn accumulation to Fe accumula-tion in the countryside subjects was investigated, be-cause it is known that Mn absorption in the intestine conflicts with Fe absorption, and that high absorption of

Mn suppresses Fe absorption [17,18]. However, as shown in Fig. (3), subjects showed high levels of both Mn and Fe accumulations, and the Mn level was signifi-cantly correlated with the Fe level. This result suggested that high accumulations of Mn and Fe may not always reflect levels of intestinal absorption alone. Furthermore, the Mn level was also correlated with the Pb level and this with the Cd level. The Fe level was correlated with the Al level at a high significance. These results suggest that these minerals may enter the body through the same route.

2. Measurements of Urinary 8-OHdG

(1) To know oxidative stress, urinary 8-OHdG levels of countryside subjects were assayed and compared with those of Japanese subjects. As shown in Table 5, the countryside subjects showed 13.5±5.8 ng/mg Crea, whereas the Japanese subjects were 8.5±3.4 ng/mg Crea, a significant difference (p<0.001). This finding suggests that the countryside subjects may be in high oxidative stress as compared with the Japanese subjects. Because subjects of all investigated places showed such high lev-els, with Gobisumber subjects demonstrating the highest level, this phenomenon may be prevalent in large areas of Mongolia.

(2) The relationship of Mn accumulation to urinary 8-OHdG levels was investigated. As shown in Fig. (4), the Mn level was significantly correlated with the 8-OHdG level, with Fe, Pb, Cd and Al levels also correlated. This finding is indicative of these minerals leading towards high oxidative stress in the subjects. In this Figure, the relationship of Se level to the 8-OHdG level is also shown. The Se level was generally low compared to that of the Japanese subjects as described above, and this level exhibited a reverse correlation to the 8-OHdG level. It suggests that the low Se level may cause a re-duction of anti-oxidant potential, resulting in high oxida-tive stress.

3. Association of Hair Mineral Accumulations with Park-insonism and Arthritis

In Mongolia, Parkinsonism is prevalent and because it is known that a high accumulation of Mn in the body induces Parkinsonism, the association of hair mineral accumulation with the disease was investigated. Twenty-one patients (10 from the country sides and 11 in Ulaanbaatar) were selected by native researchers. The Ulaanbaatar patients were more serious than the countryside patients. They transferred from rural areas to Ulaanbaatar 5-8 years ago in order to receive treatment at family clinics. They lived in a concrete apart-ment house and did not go out. Conversely, the countryside patients had suffered from the disease for 3-5 years, and lived in gers or small houses and spent for a relatively long time outdoors every day. Arthritis (rheumatoid arthritis, os-teoarthritis, spondylitis, and degenerative joint disease) were also prevalent here. Because it is said that arthritis is caused by harmful minerals such as Pb, Cd and Al, the relationship of these minerals to the disease was also investigated. Twenty-five patients (20 from the country sides and 5 from Ulaanbaatar) were selected. The Ulaanbaatar patients were severe, and did not go out but stayed indoors daily because


Table 2. Accumulated Minerals in Hair of Mongolian Countryside Healthy Subjects, and Japanese Standards and Japanese

Healthy Subjects

Japanese Standard Japanese Healthy Subject n=81 Countryside Healthy Subjects n=214 Significance

Mean ± SD Mean ± SD

Cd ppb 3.3 - 25.0 8.2 ± 7.6 46.0 ± 45.5 ***

Hg ppm 1.4 - 5.3 3.83 ± 1.78 0.14 ± 0.13 ***

Pb ppb 153 - 1392 548 ± 432 1789 ± 1705 ***

As ppb 13 - 71 48 ± 46 38 ± 37 ns

Be ppb 0.12 - 0.94 0.26 ± 0.12 0.70 ± 0.66 ***

Al ppm 1.9 - 8.5 3.7 ± 2.4 10.0 ± 7.0 ***

Na ppm 3.1 - 22.9 18.6 ± 24.3 92.9 ± 97.7 ***

K ppm 1.9 - 23.6 18.2 ± 16.3 34.9 ± 28.8 ***

Mg ppm 30 - 156 92 ± 88 209 ± 186 ***

Ca ppm 314 - 1582 876 ± 855 815 ± 806 ns

P ppm 96 - 142 119 ± 36 111 ± 30 ns

Se ppb 405 - 784 661 ± 152 322 ± 97 ***

I ppb 71 - 626 458 ± 405 581 ± 502 ns

Cr ppb 12 - 106 70 ± 55 126 ± 73 ***

Mo ppb 14 - 37 32 ± 14 57 ± 55 ***

Mn ppb 53 - 248 109 ± 73 2067 ± 2028 ***

Fe ppm 4.4 - 8.7 5.6 ± 1.8 15.4 ± 7.5 ***

Cu ppm 13.4 - 60.2 22.4 ± 14.6 13.3 ± 5.9 ***

Zn ppm 108 - 184 147 ± 43 162 ± 86 ns

V ppb 4.5 - 66.1 22.7 ± 19.2 25.5 ± 19.4 ns

Co ppb 2.4 - 17.0 6.4 ± 4.2 17.6 ± 16.8 ***

Ni ppb 82 - 902 390 ± 444 167 ± 155 ***

Li ppb 0.4 - 11.0 3.3 ± 2.1 13.0 ± 11.1 ***

Ge ppb 44 - 144 73 ± 30 31.5 ± 24.8 ***

B ppb 109 - 487 429 ± 314 622 ± 673 **

Br ppm 0.9 - 19.0 5.9 ± 5.7 3.2 ± 2.7 ***

Significance means the difference of countryside healthy subjects to Japanese healthy subjects. ** p<0.01, *** p<0.001, ns : not significant

Table 3. Comparison of Hair Mineral Levels between Males and Females of Countryside Healthy Subjects

Male Subjects

n=111

M ± SD

Female Subjects

n=133

M ± SD

Significance

Cd ppb 57.4 ± 51.1 30.3 ± 28.9 ***

Hg ppm 0.16 ± 0.15 0.12 ± 0.13 *

Pb ppb 2194 ± 2088 1251 ± 1087 ***

As ppb 59.6 ± 40.8 19.3 ± 13.4 ***


(Table 3) Contd….

Male Subjects

n=111

M ± SD

Female Subjects

n=133

M ± SD

Significance

Be ppb 0.78 ± 0.97 0.63 ± 0.30 ns

Al ppm 12.0 ± 7.4 8.9 ± 7.7 ***

Na ppm 65.8 ± 63.4 114.2 ± 101.4 ***

K ppm 29.2 ± 25.4 40.3 ± 32.8 **

Mg ppm 109 ± 107 287 ± 240 ***

Ca ppm 402 ± 381 1138 ± 1105 ***

P ppm 115 ± 22 108 ± 35 ns

Se ppb 381 ± 88 294 ± 88 ***

I ppb 395 ± 340 728 ± 711 ***

Cr ppb 145 ± 82 111 ± 62 ***

Mo ppb 60 ± 55 55 ± 48 ns

Mn ppb 1818 ± 1410 2263 ± 2238 ns

Fe ppm 16.8 ± 8.0 14.7 ± 8.8 *

Cu ppm 12.6 ± 4.4 14.1 ± 7.8 ns

Zn ppm 137 ± 36 181 ± 107 ***

V ppb 25.0 ± 19.1 25.9 ± 19.8 ns

Co ppb 12.6 ± 12.0 21.6 ± 20.0 ***

Ni ppb 125 ± 100 199 ± 176 ***

Li ppb 12.8 ± 11.0 13.1 ± 12.0 ns

Ge ppb 29.0 ± 23.3 33.5 ± 25.8 ns

B ppb 676 ± 564 581 ± 579 ns

Br ppm 3.8 ± 2.1 2.7 ± 2.2 ***

* p<0.05, ** p<0.01, *** p<0.001, ns : not significant

Table 4. Hair Mineral Levels of Countryside Healthy Subjects

Gobisumber

n=41

M ± SD

M Erdenet

n=45

M ± SD

Murun

n=65

M ± SD

Aleg-erden

n=55

M ± SD

Tsagan-uul

n=8

M ± SD

Mn ppb 3200 ± 3134 1526 ± 1418 1975 ± 1876 2008 ± 1617 2292 ± 1907

Fe ppm 22.1 ± 11.2 14.4 ± 7.6 13.1 ± 7.3 15.9 ± 6.3 12.6 ± 5.8

Pb ppb 2455 ± 2326 972 ± 878 1285 ± 1146 2010 ± 1986 2236 ± 1460

Cd ppb 59 ± 53 46 ± 42 38 ± 33 32 ± 31 26 ± 17

Al ppm 12.8 ± 8.6 9.1 ± 6.4 7.8 ± 6.4 11.9 ± 6.1 6.2 ± 5.6

Hg ppm 0.20 ± 0.11 0.17 ± 0.15 0.14 ± 0.13 0.13 ± 0.11 0.17 ± 0.11

Se ppb 349 ± 120 337 ± 122 311 ± 75 294 ± 74 283 ± 107


Fig. (2). The relationship of hair mineral levels to ages in countryside healthy subjects.

Table 5. Comparison of Urinary 8-OHdG Levels between Countryside and Japanese Healthy Subjects

n

8-OHdG (ng/mg Crea)

M ± SD Significance to Japanese

Gobisumber 41 17.2 ± 6.2 ***

Erdenet 45 10.2 ± 3.9 *

Murun 65 13.2 ± 7.2 ***

Aleg-erden 55 13.8 ± 4.9 ***

Tsagan-uul 8 12.7 ± 6.2 **

( average) 13.5 ± 5.8 (***)

Japanese 81 8.5 ± 3.4

* p<0.05, ** p<0.01, *** p<0.001

of arthralgia, lumbago and back pain. The countryside patients were not as severe, and could work a little.

(1) As shown in Fig. (5), countryside patients with Parkin-sonism and arthritis showed higher levels in Mn, Fe, Pb, Cd and Al accumulations than countryside healthy sub-jects. The levels of urinary 8-OHdG were also higher in these patients than in healthy subjects. This finding sug-gests that the high accumulation of these minerals may have an association with Parkinsonism and arthritis through increasing of oxidative stress. In particular, Mn accumulation was higher in Parkinsonism than in arthri-tis, and Fe, Pb, Cd and Al accumulations were higher in

arthritis than in Parkinsonism, although these differ-ences were not always significant.

(2) While, as shown in this Figure (Fig. 5), Ulaanbaatar patients showed lower levels in these minerals than countryside patients. The same tendency was also ob-served in the urinary 8-OHdG level. As described above, most of the Ulaanbaatar patients stayed indoors every day. Meanwhile, countryside patients spent for a long time outdoors every day, suggesting that life style may affect the different tendencies.

(3) Furthermore, because Ulaanbaatar healthy subjects showed variable levels in the accumulation of these


Fig. (3). The correlation of hair mineral levels in countryside healthy subjects.

Fig. (4). The relationship of urinary 8-OHdG levels to hair mineral levels in countryside healthy subjects.


Fig. (5). Accumulated hair mineral levels and urinary 8-OHdG level in the patients with Parkinsonism and arthritis, and in the healthy sub-

jects of countryside, Ulaanbaatar (outdoor workers and indoor workers) and Japanese.

minerals, subjects were divided into outdoor and indoor workers, and accumulation tendencies were compared between them. As shown in this Figure, outdoor workers generally demonstrated higher levels in minerals than indoor workers. The same tendency was also observed in the level of urinary 8-OHdG. This finding suggests that a certain outdoor factor may affect the high accu-mulation of these minerals in outdoor people.

4. Measurements of Minerals Contained in Drinking Wa-ter, Sheep Meat, Wild Grasses and Soil

(1) To know how these minerals entered the human body, the minerals contained in drinking water (well water) were analyzed and compared with that of the public wa-

ter supply in Tokyo. The results are shown in Table 6. Mineral levels contained in the well waters were vari-able among the investigated places. As a whole, the dif-ferences between Mongolian drinking waters and that of Tokyo were not so large. Therefore, the high accumula-tion of these minerals in the hair of Mongolian subjects could not be explained by the drinking water.

(2) Generally, Mongolian people eat large amounts of sheep meat every day, while Japanese people eat cattle meat 1-2 times a week. Thus, minerals contained in Mongolian sheep meat from Murun were analyzed, and levels com-pared with those in meat from Japanese cattle raised near Tokyo. The results are shown in Table 7. Mongo-lian sheep meat contained Mn, Fe, Pb, Cd, Al and some


other minerals at very high levels, as compared with that of Japanese cattle meat. This finding suggested that the high accumulation of these minerals in the hair of Mon-golian subjects may be due to the high intake of sheep meat.

(3) Because Mongolian sheep meat contained these miner-als at high levels, those contained in Mongolian wild grasses from Murun were analyzed, and the results compared with that of wild grasses from the Tokyo area. The Mongolian wild grass sample was consisted of pars-ley and shepherd’s pasture, the main plants in Murun and eaten by sheep, cattle and goats. Wild grasses from near Tokyo contained parsley, clover and shepherd’s pasture, the most common wild grasses from there. As shown in Table 8, Mn, Fe, Cd, Pb, Al and some other

minerals were contained at higher levels in the Mongo-lian wild grasses than in the grasses of the Tokyo area. This result indicated that the high levels of minerals in sheep meat may be induced by eating these grasses.

(4) Minerals contained in the soil of the investigated places were also analyzed, and results compared with those of soil in the Tokyo area. Samples were collected from sur-face soil at 3 different points in each place. The averages are shown in Table 9. There were some differences among the investigated places. The soil sample from Gobisumber contained Fe, Pb, Cd, Al and Li at rela-tively high levels, and was compatible with the high ac-cumulation of these minerals in subjects from here. As a whole, Mongolian soil samples contained these minerals

Table 6. Minerals Contained in Drinking Water of Investigated Places of Mongolia and Public Water of Tokyo

Gobisumber

pH : 8.45

Ulaanbaatar

7.93

Erdenet

7.86

Murun

7.75

Aleg-erden

7.76

Tsagan-uul

7.8

Tokyo

8.06

Cd ppb 0.01 0.01 0.02 0.01 0.01 0.01 0.02

Hg ppb 0.12 0.07 0.09 0.02 ND ND 0.23

Pb ppb 0.03 0.01 0.01 0.03 0.01 0.01 0.09

As ppb 1.22 1.55 0.76 0.77 0.35 0.22 0.28

Be ppb ND ND ND 0.002 ND ND ND

Al ppb 0.43 1.11 0.09 0.83 1.55 1.28 5.78

Na ppm 114.7 1.7 3.5 21.8 18.4 17.2 13.8

K ppb 862 285 638 1660 1534 1350 2400

Mg ppm 6.5 0.6 4.7 3.6 2.7 2.6 5.9

Ca ppm 34.5 4.3 21.3 35.7 31.9 33.4 19.4

Se ppb 0.14 0.11 0.07 0.21 0.06 0.02 0.18

Cr ppb 0.11 0.04 0.04 0.46 0.18 0.15 0.15

Mo ppb 7.06 0.25 1.47 3.51 3.03 2.65 0.55

Mn ppb 2.73 4.92 2.87 0.54 1.44 2.11 0.11

Fe ppb 0.14 0.99 0.03 1.32 1.19 0.88 1.32

Cu ppb 0.09 0.03 0.84 0.66 0.62 0.73 1.29

Zn ppb 1.46 2.08 25.95 1.86 1.54 1.32 7.33

V ppb 0.43 0.09 0.39 0.29 0.38 0.14 1.54

Co ppb 0.02 0.01 0.02 0.04 0.04 0.03 0.06

Ni ppb 0.23 0.26 0.13 0.08 0.12 0.15 0.07

Li ppb 47.3 0.44 1.12 4.54 3.64 2.11 1.83

Ge ppb 0.06 0.01 0.01 0.01 0.01 0.02 0.04

Sb ppb 0.02 0.02 0.03 0.02 0.01 0.01 0.01

Ba ppb 4.5 2.2 9.2 21.2 14.4 15.1 2.9

Sr ppb 526 33 139 130 128 154 85

ND : not detected.


Table 7. Minerals Contained in Mongolian Sheep Meat and

Japanese Cattle Meat

Mongolian Sheep Meat Japanese Cattle Meat

Cd ppb 11 1

Hg ppb 1 2

Pb ppb 230 13

As ppb 112 28

Be ppb 8.9 ND

Al ppm 274 70

Na ppm 1393 2115

K ppm 9419 11080

Mg ppm 646 659

Ca ppm 269 142

Se ppb 81 757

Cr ppb 586 94

Mo ppb 57 32

Mn ppb 9963 487

Fe ppb 350900 66570

Cu ppb 3566 2897

Zn ppm 131 200

V ppb 783 14

Co ppb 124 15

Ni ppb 295 31

Li ppb 226 5

Ge ppb 37 11

Sb ppb 11.3 1.5

Ba ppb 3033 174

Sr ppb 1025 199

ND: not detected

at higher levels than from Tokyo soil, although the Mn level was not high. Conversely, Se and Hg levels were lower in Mongolian soil than in Tokyo soil, indicating that the low accumulation of Se and Hg in Mongolian hair may be associated with the low concentration of these in the soil. In this Table, the result of measurement of wind-drifted soil was also added. This sample was obtained at the road sides in Murun. Wind-drifted soil contained Mn, Fe, Pb, Cd and Al at very high levels, as compared with the simple soil sample from Murun. This finding suggests that these minerals may also be con-tained in the wind pollution, and furthermore, that the certain outdoor factor as described above may be the wind pollution.

Table 8. Minerals Contained in Wild Grasses of Mongolia

and Tokyo Area

Mongolia Grasses Tokyo Area Grasses

Cd ppb 27 8

Hg ppb 99

Pb ppb 526 122

As ppb 48 23

Be ppb 5.0 2.1

Al ppm 441 132

Na ppm 25 24

K ppm 15260 13825

Mg ppm 3588 1925

Ca ppm 17485 1211

Se ppb 37 120

Cr ppb 519 38

Mo ppb 1908 23

Mn ppm 224 128

Fe ppm 210 16

Cu ppm 25 4

Zn ppm 35 33

V ppb 490 45

Co ppb 115 121

Ni ppm 0.8 3.9

Li ppb 116 73

Ge ppb 20 13

Sb ppb 8.9 4.2

Ba ppm 34 13

Sr ppm 96 6

ND: not detected.

DISCUSSION

As previously reported, Mongolian people were in high oxidative stress, as compared with Japanese people, which may mainly have been induced by a high accumulation of Mn in the body [5]. Excessive Mn accumulation causes health problems. Chronic manganese poisoning mainly ap-pears in the central nervous system. Mn readily crosses the blood-brain barrier [19] and generates cytotoxic reactive oxygen species (ROS) [20,21], and induces a severe reduc-tion of dopamine in astrocytes [22]. A marked decrease of dopamine causes Parkinson’s disease [23]. In Mongolia, Parkinsonism is highly observed. Thus, it was considered that the high Mn accumulation may have affected the preva-lence of this disease.


This (2nd

) report revealed that not only Mn, but Fe, Pb, Cd and Al were all accumulated in the hair at high levels. Because these mineral accumulations were correlated with urinary 8-OHdG levels, it is likely that they also increased oxidative stress. This tendency was observed even in young people of 10-19 years. Fe is an essential mineral, together with Cu and zinc (Zn). These minerals are necessary for the activity of anti-oxidant enzymes. Fe is integrated into cata-lase. Cu and Zn are components of superoxide dismutase. In this study, Cu accumulation showed relatively low level, and Zn was a similar level to that of the Japanese. However, Fe demonstrated a 2.8 fold higher level than the average of the Japanese (from 1.0 fold to 6.8 fold high levels). Excessive Fe reacts with hydrogen peroxide (H2O2), called Fenton’s reac-tion, and induces hydroxyl radical which is one of the most dangerous ROS. Pb, Cd and Al are known to be harmful minerals, and dangerous to the body. In particular, Pb and Cd contribute to high oxidative stress by catalyzing the for-mation of ROS, increasing lipid peroxidation, and depleting glutathione [24]. Major sources of Pb are dust, water, paint, cosmetics and food supplements. Exposure to Pb elevates 8-OHdG, and produces Alzheimer’s disease-related -amyloid peptide in the aging brain [25]. Cd is contained in grain and tobacco, but it is highly generated by industrial practices. It is widely used for electroplating, galvanizing, and in batter-ies. Cd elevates lipid peroxidation in tissues soon after expo-sure, resulting in toxicity to liver, kidneys, brain, lung, heart and central nervous system. Free radical scavengers and an-tioxidants are useful in protecting against Cd toxicity [26]. Al is also a contributor to neurological disorders and age-related dementia such as Alzheimer’s and Parkinson’s dis-eases [20]. Al enters the body through cookware and proc-essed food like cheese and soy-based milk products. The exact mechanism of Al toxicity is not known, but it is con-sidered that Al increases oxidative stress and enhances in-flammation, leading to impaired neurological function [27].

Hg is also known to be harmful mineral. But, in this study, the Hg level in hair was very low. The Hg concentra-tion in Mongolian soil was also low. Yasutake et al. [28] stated that the high accumulation of Hg in the Japanese was due to a high intake of large wandering fish such as bonito and tuna because Hg is usually contained in such fish. Mon-golian people rarely eat fish so it was first thought that the low level of Hg in hair might be due to the low intake of fish, but it is likely that the low level in hair may have a con-nection with low concentration in the soil. A low accumula-tion of Hg is favorable to the human body, but a low level of Se is disadvantageous because Se is a component of glu-tathione peroxidase, an important anti-oxidant enzyme. In this study, Se level was generally low in Mongolian hair. Its level decreased as going northward, and was very low in Tsagan-uul subjects. More than seventy years ago, Se insuf-ficiency in food caused Keshan disease in the north-eastern area of China [29], where Se is known to be in scant amount. In this study, the Se component in the soil of each investi-gated area was also low. Therefore, one of the reasons for high oxidative stress in Mongolian subjects may be the pov-erty of Se. Furthermore, this study also found a high accu-mulation in other minerals like Cr, Mo, Li and Co, but the influence of them on the body could not be elucidated.

In Mongolia, Parkinsonism and arthritis are prevalent, although the incidences of these diseases have not yet been assayed. Subjects with these diseases showed high levels in urinary 8-OHdG, indicating that oxidative stress may con-tribute to these diseases. They are induced by different mechanisms, but may be triggered or enhanced by harmful minerals [10,11] through the high oxidative stress [12,13]. Milachowaski et al. [10] stated that idiopathic necrosis of the head of the femur is connected with heavy-metal toxicity due to Cd, nickel and Pb. Mirshafiey et al. [12] described that increased ROS production leads to tissue damage in rheuma-toid arthritis. Shin et al. [13] reported that ROS caused apop-totic cell death in fibroblast-like synovial cells in rheumatoid arthritis. In order to suppress arthritis, anti-oxidant agents are often effective [30]. In considering why these diseases are prevalent in so many in Mongolia, it may be explained by the high accumulation of harmful minerals and by high oxi-dative stress.

Now, routes by which these minerals entered the body should be discussed. The way through drinking water was discredited as shown in Table 6. Thus, the minerals con-tained in meat were assayed. Minerals are originally con-tained in soil, and enter plants, animal meats and then human body. Mn is contained in food materials such as wheat, grain, legume, green laver, tea leaves, etc. The amount of Mn contained in animal meats is generally small. The previous study calculated the amount of Mn intake in Mongolian peo-ple using the Standard Tables of Food Composition in Japan (the Ministry of Education, Culture, Sports, Science and Technology of Japan, 2007) [5]. However, it was noticed in this study that the content of Mn in Mongolian sheep meat was entirely different from that of the Japanese Standard Tables of Food Composition. It is surprising that Mongolian sheep meat contained these minerals at extremely high levels as shown in Table 7. Thus, the high accumulation of these minerals in the hair of Mongolian people can be explained by sheep meat. These minerals were really contained in soil and wild grasses at high levels as shown in Tables 8 and 9. It is conceivable that these minerals may be concentrated in sheep body.

On the other hand, there is possibly another route. Re-cently, Finkelstein et al. [9] reported the relationship be-tween traffic-derived Mn air pollution and Parkinson’s-like disorder. During the past ten years, the number of vehicles has increased in Ulaanbaatar, Erdenet and Murun, but the traffic-derived Mn air pollution is not applicable in Aleg-erdene or Tsuganuul, which are small villages in green field, with no traffic air pollution. Now, our guess is not traffic air pollution but sandy wind pollution. Sandy wind blows from the dry western land to the investigated areas, and also reaches Japan. Tottori Prefecture in Japan is the first place reached. This prefecture measured the levels of minerals contained in sandy wind during the sandy wind season from January to April in 2007, and recently reported the results as follows; the average level of Mn increased to 14.7 fold, Fe 30.5 fold, Al 10.0 fold, Cd 3.4 fold and Pb 4.1 fold, com-pared to those of the non-sandy wind season (report by Tot-tori Prefecture Institute of Public health and Environmental Science, April, 2008). This report has relevance in under-standing the high accumulation of these minerals in Mongo-lian subjects. Sun et al. [31] reported that Mn toxicity is due


to chronic inhalation of high concentrations of airborne Mn. Nemmar et al. [32] assayed the absorption of inhaled pollut-ant particles into systemic circulation using

99mTechnetium-

labeled ultrafine carbon particles, and stated that radioactiv-ity was already detected in blood at 1 minute, and reached a maximum at between 10 and 20 minutes. Concerning Al, Michalke et al. [33] stated that the main pathway of Al expo-sure is via inhalation, comprising up to 90%. In this study, it was noticed that wind-drifted soil contained these minerals at very high levels, as shown in Table 9. This result suggested that sandy wind pollution may be one noteworthy route for such high accumulations.

Finally, why Ulaanbaatar indoor workers showed low levels in these minerals as compared to outdoor workers, as shown in Fig. (5), should be described. Most countryside healthy subjects and the Ulaanbaatar outdoor workers spent outdoors for long periods of time every day. Because miner-als were contained in wind-drifted soil at very high levels, it is likely that they were highly exposed to the sandy wind pollution. In contrast, the indoor workers were not so much exposed, although they breathed the same air. In comparing mineral levels between males and females, because males may have been exposed to outdoor air pollution for a longer time than females, males showed higher levels in Fe, Pb, Cd and Al accumulations than females as shown in Table 3,

Table 9. Minerals Contained in Soil of Investigated Places and Tokyo Area

Gobisumber Ulaanbaatar Erdenet Murun Aleg-Erden

Tsagan-

Uul Wind-Drifted Soil in Murun Tokyo

pH 7.42 8.36 7.72 8.34 7.51 7.42 8.53 7.78

Cd ppb 225 92 124 100 125 145 280 68

Hg ppb ND ND ND ND ND ND ND 88

Pb ppm 126 221 31 65 39 28 180 27

As ppm 7.0 5.8 24 2.5 1.7 1.4 7.5 5.5

Be ppm 1.8 1.5 1.2 1.3 1.1 0.2 2.8 1.7

Al ppm 25460 10360 13538 20520 17600 10190 42200 7080

Na ppm 17800 19160 19360 19260 17050 9276 18450 6979

K ppm 23720 14860 12700 15240 8773 7791 11070 4879

Mg ppm 5278 4355 4270 3705 3659 3627 3907 2899

Ca ppm 2902 9569 19990 25090 21650 19290 28890 17130

Se ppb 115 105 99 67 48 41 76 686

Cr ppm 13.0 22 38 25 62 34 28 13

Mo ppb 725 644 13640 693 591 530 1934 301

Mn ppm 671 688 573 531 522 523 1043 696

Fe ppm 38310 19560 23200 16790 16961 15450 58960 5900

Cu ppm 4.0 9.4 464.3 5.6 7.9 10.1 23.7 36.2

Zn ppm 35 52 58 36 54 43 45 56

V ppm 33 38 118 53 65 78 84 44

Co ppm 5.5 7.1 10.0 8.6 7.0 7.4 14.8 3.4

Ni ppm 4.0 5.6 6 10 13 16 14 31

Li ppm 27 14 10 7 9 8 9 11

Ge ppm 1.3 1.4 2.2 1.5 2.1 0.8 1.8 2.6

Sb ppb 406 1522 7107 293 190 155 535 4063

Ba ppm 396 334 307 404 340 272 405 150

Sr ppm 270 149 123 247 202 184 409 66

The data are averages of three samples which were obtained at 3 points of each investigated place. Wind-drifted soil was obained at the road side soil which was accumulated by the wind in Murun. ND: not detected.


although Mn level was relatively high in females. Ulaan-baatar patients with Parkinsonism and arthritis also showed lower levels than countryside patients. This may also be ex-plained by sandy wind pollution because the Ulaanbaatar patients spent every day indoors. In Mongolia, mineral ac-cumulation in the body has not yet been assayed systemati-cally, but Bodienkova et al. [34] recently reported that envi-ronmental pollution increased Pb level in the serum of chil-dren, which resulted in neurological diseases in these chil-dren.

In conclusion, Mongolian people are in high oxidative stress. High accumulations of Mn, Fe, Pb, Cd and Al may induce oxidative stress and cause a high prevalence of Park-insonism and arthritis. The main route for such high accumu-lation in the body may be through eating sheep meat. Sandy wind pollution may also contribute. These conditions may also be connected to other non-communicable diseases here, resulting in early aging and a short life span of the people. In order to suppress high oxidative stress, the accumulation of these minerals in the body should be avoided.

ABBREVIATIONS

8-OHdG = 8-hydroxy-2'-deoxyguanosine

ROM = Reactive oxygen metabolites

MDA-LDL = Malondialdehyde-modified low density lipoprotein

ROS = Reactive oxygen species

ICP-MS = Inductively coupled plasma mass spectrometry

Al = Aluminum

As = Arsenic

Cd = Cadmium

Cr = Chromium

Co = Cobalt

Cu = Copper

Fe = Iron

Hg = Mercury

Li = Lithium

Mn = Manganese

Mo = Molybdenum

Pb = Lead

Se = Selenium

Zn = Zinc

ACKNOWLEDGMENTS

The authors are grateful for the cooperation of the staff in Mongolia in the management of this study. This study was supported by Grants from the Ministry of Education, Cul-ture, Sports, Science and Technology, Japan.

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Received: April 19, 2010 Revised: May 17, 2010 Accepted: May 31, 2010

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