Sustainability Issue #1 January 2009

Water is vital for all life on earth. People can survive several weeks without food, but only a few days without water. Sweden is one of the relatively few countries where both surface water and groundwater of good quality are readily available. In many countries,  most of all in the developing world, access to clean drinking water is becoming increasingly problematic because of overpopulation and greater use of water for industrial processes and agriculture. More and more people are becoming dependent on groundwater since surface water in sufficient volume or an adequate degree of purity is not available. Groundwater has generally been regarded to be of good quality, but substances such as arsenic, manganese, fluoride, uranium and radon are naturally present in rock and can be dissolved by the surrounding water, giving rise to elevated contents, especially in drilled wells. 

Arsenic in drinking water 

A summary is given below of the health risks that are associated with arsenic in drinking water and the research conducted at the Karolinska Institute KI, in cooperation with many research teams all over the world. Research at Karolinska Institute is of world class as regards the health risks of arsenic. The focus is on risk groups and risk factors. We have also started to be interested in manganese which is considerably more common in drinking water than arsenic. Small children are presumed to be a high risk group since it takes several months after birth before children can regulate the uptake of manganese in the intestine and to excrete any excess with the bile. Infants can therefore take up too much manganese from the water used for the preparation of breast milk substitute and gruel. We have insufficient knowledge concerning the effects. 

In wells drilled in rock 

Arsenic is an element and occurs naturally in the bedrock. In areas with arsenic-containing minerals, arsenic may be dissolved into groundwater. Elevated arsenic contents primarily occur in wells drilled in rock. Globally, many millions of people use drinking water with such a high arsenic content, often several hundred microgrammes (Ug) per litre, that there is a risk of serious health effects. Worst hit are poor countries such as Bangladesh, India, parts of South America and Inner Mongolia, but elevated contents are found in many countries, even in Sweden, where the bedrock contains arsenic, for example in Västerbotten and Västernorrland, and also in Enköping, Västerås and Smedjebacken.

Arsenic affects foetuses and children 

Inorganic arsenic is very toxic and prolonged exposure can give rise to a number of health effects. The earliest symptoms of chronic exposure are changes in skin pigmentation and hyperkeratosis, i.e. thickening of the outermost layer of the skin, especially on the palms and on the soles of the feet. Arsenic is also highly carcinogenic and increases the risk of tumours in the skin, lungs and bladder, and possibly also in the liver and kidneys. 

Although we showed more than ten years ago that arsenic easily passes from the placenta to the foetus, knowledge of the effects of arsenic on the health and development of the child is limited. We have therefore focused our research on this area

and have ongoing studies in e.g. Argentina and Bangladesh. It is hoped that improved knowledge can speed up measures to reduce exposure to arsenic. In the villages up in the Andes, people have been drinking water with elevated arsenic contents for thousands of years. In Bangladesh, perhaps one half of the ca 10 million wells installed over the past decades, partly with the help of development funds, have been found to have high arsenic contents. We have shown that arsenic in drinking water can affect the development of the foetus and can in serious cases cause the death of the foetus. One important finding is that breast feeding gives protection against further exposure since breast milk contains very little arsenic. Very recently, however, reports have come in that arsenic can also affect the development of the child, and our continued research focuses on elucidating the various risk factors and especially the susceptible ages. 

Arsenic metabolised in the body 

Inorganic arsenic which we ingest with drinking water is metabolised in the body through methylation into dimethyl arsenic acid (DMA) which is excreted with the urine and can therefore be regarded as a detoxification mechanism. Reactive intermediate products such as monomethyl arsenic acid (MMA) can however be formed, and it is therefore essential that methylation should proceed all the way to DMA and not stop at MMA. 

The metabolisation of arsenic occurs through the single-carbon metabolism of the body. Through this reaction, a seemingly small and insignificant methyl group (consisting of one carbon atom which binds three hydrogen atoms) is transformed from an activated form of the amino acid methionine into a number of different compounds to form essential compounds such as creatine (which stores and supplies energy in the muscles) and different forms of methylated DNA (which controls the activity of different genes). The single-carbon metabolism, in the same way as the methylation of arsenic, greatly varies between individuals, depending on both hereditary factors and various environmental factors. We have found that women, in general, have more effective methylation of arsenic than men, and that this may be the explanation why men run a higher risk than women of developing effects of arsenic in the skin and possibly also other effects. The Indians in the Andes have very effective methylation of arsenic, and we have shown, as the first research team, that this is dependent on a special genotype, perhaps developed through selection over many centuries of exposure. This research considerably enhances understanding of how arsenic is detoxified in the body. 

The single-carbon metabolism is dependent on folic acid and Vitamin B12 for the recycling of methionine from the homocysteine formed when SAM releases a methyl group and which functions as a stop light for further methylation reactions. It may therefore be assumed that women in Bangladesh, with malnutrition and a monotonous diet (mainly rice), have a worse capacity to detoxify arsenic than we in the western world. However, this does not appear to be the case, which can probably be explained by the fact that women can influence methylation of arsenic in different ways. Since the single-carbon metabolism is of fundamental importance for the development of the foetus, women can, through the influence of the female sex hormone oestrogen, produce choline which can help recycle methyl groups, especially when there is folic acid deficiency. This capacity to synthesise choline increases during pregnancy, which results in more effective methylation of arsenic during pregnancy. We have seen that effectivisation of the single-carbon metabolism during pregnancy and breast feeding also result in effective methylation of arsenic by the breast-fed child. The aim of our further research is to show whether this also protects against the toxic effects of arsenic during early childhood, which would obviously be very beneficial.

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