Water, Elements UPDATES

Adding Fluoride To Water Supplies —

This is such a contentious subjects. The observation that towns in the North East of England which were close together had different teeth decay levels lead to the observation that the fluoride content of the drinking water was the determinant.

The next step was to fortify the drinking water of fluoride deficient water. ( Germany, Ireland, Portugal, Spain, UK and USA) or table salt ( France ). Water fluoridation is intended to reduce social inequality in the provision of fluoride.

There has been much debate on this subject which has generated heat and dismay. Is this mass medication or acting within commonly found natural limits. If a medicine then the standard of proof has to be that of a medicine.

In the BMJ this topic has been reviewed

Cheng, Chalmers, Sheldon ( 2007 ) Adding fluoride to water supplies BMJ vol 335, 699-702

A review commissioned by the Department of Health in England at the University of York looked at the evidence for benefit of adding fluoride to drinking water on dental health. Whilst there are many papers on this subject many did not meet proper scientific standards.

A problem is fluorosis, teeth mottling which was visible in 48% and aesthetically concerning in 12% of people studied at 1 part per million.

A claim for an increase in bladder cancer from Taiwan proved to be a difficult one to prove or disprove and the evidence is at the best marginal.

Studies become more difficult because of the wide availability of fluoride containing toothpastes. The benefit in young children appears to be 24%.

Fluoride is the main factor that alters the resistance of teeth to acid attack and sugar in plaques. Caries are reduced fluoride which

Reduces and inhibits the dissolution of enamel

Promotes remineralisation

Alters the ecology of the plaque.

Fluoride is most effective when used topically

Copper Binding —

In a recent copy of Nature Chemical Biology Davis and Halloran discuss cellular copper ion chemistry. Transition metals such as zinc, copper and iron are necessary to reach intracellular concentration of tens to hundreds of micromolar. Few if any of these ions are thought to be ‘free’ or readily accessible in terms of their thermodynamic availability or reaction chemistry. The mechanisms by which cells control the metal occupancy of a given metal-binding site—that is, how metalloenzymes acquire the correct metal ion at the right time in cellular growth—are emerging through physiochemical characterization of a range of conserved metal trafficking pathways.

The regulation of metal ion availability requires the concerted activity of numerous metal receptors, including metal transporters, metallochaperones and metalloregulatory factors.

Mechanistic and structural insights into the chemistry of cellular copper-trafficking machinery have predominately focused on cysteine (that is, thiol)-rich CuCI) sites which are associated with inherited diseases of copper metabolism.

In a series of recent studies characterizing methionine-rich domains of copper trafficking proteins, some unexpected copper-thioether chemistry is emerging. As was the case for cysteine thiolate-rich sites, the CuCI) coordination chemistry of such proteins is quite distinct from that seen in copper enzymes.

Two fundamental differences are emerging between the two classes: they each function in chemically distinct subcellular compartments, and they use quite different electrostatic contributions to achieve Cu(I) binding selectivity and transfer.

Most of the cysteine-rich copper sites characterized to date are found in reducing intracellular compartments, whereas an abundance of methionine-rich copper sites are found in the oxidizing compartments and the extracellular milieu.

One important feature of the methionine-rich sites and motifs is their selectivity against the two most abundant intracellular transition metal ions: zinc and iron. Notably, the +2 ions of these metals are not favoured for binding in the methionine-rich sites, but hundreds of examples of zinc and iron ions bound to CXXC motifs in higher-coordinate or metal-cluster sites can be found in the metalloprotein literature (for example, in zinc finger proteins and iron-sulfur proteins).

As our understanding of the methionine-rich chemistry expands to include extracytosolic proteins, a broad picture is emerging of biological cuprous coordination and ligand-exchange chemistry. Different coordination motifs seem to be tailored to different pathways and cellular environments in order to preserve copper-specific recognition within a robust metal-binding site. A corollary to this idea, however, is the consideration that metal-trafficking sites may also be responsive to changing cellular environments, as oxidative bursts may release copper or zinc ions from cysteine-rich (or methionine-rich) metal-binding sites as the ligating groups are oxidized and the metal-binding sites are disrupted. The interplay between the intimate coordination chemistry of each family of sites and the changing metabolic needs of the cell may well prove to be a key to unlocking the roles of metal ions in intracellular signaling processes.

Davis and Halloran 2008 A place for thioether chemistry in cellular copper ion recognition and trafficking Nature Chemical Biology vol 4 148-151.

Feed and Water Deprivation —

James P. Hogan et al review The physiological and metabolic impacts on sheep and cattle of feed and water deprivation before and during transport in Nutrition Research Reviews (2007). 20. 17-28

In traditional livestock farming systems, animals were driven across land on foot, receiving food and water en route, but nowadays they are nearly always transported by road or rail. This is usually from a farm to a market, or abattoir, or from a farm specialised in breeding stock to one reserved for fattening. Such journeys can cover thousands of km and take several days. Food and water provision is nearly always suspended during transportation and it is also common practice to deny sheep and cattle access to feed and water for several hours before transport. The practice of feed and water deprivation before transport was first called a ‘curfew by Wythes. This is distinct from undernutrition (a prolonged inadequate supply of nutrients to sustain good health and, in the case of immature or underweight animals, growth potential’) and malnutrition (‘a deficit, imbalance or excess of nutrients with consequential adverse effects on health and growth potential’)”.

The feed and water deprivation before transport has two main aims. The first is to reduce digesta load in the gastrointestinal tract in an attempt to reduce fouling of other animals, the trucks and roads over which they pass, and carcass contamination. The second, in situations where animals arc sold by weight, is to permit a more accurate prediction of carcass weight.

The short-term interruption to nutrient supply associated with feed and water deprivation will in particular affect functioning of the rumen and the rest of the digestive tract, tissue homeostasis and control of enteropathogenic bacteria by rumen microbes. Effects on metabolism in animal muscle will also influence meat quality. The process of gathering animals on a farm, holding them in yards, often with unfamiliar companions, loading them aboard unfamiliar vehicles and then transporting them, subjects the animals to multiple stressors. These are manifested by substantial increases in the circulating levels of corticosteroids, notably cortisol, and the release of catecholamines such as adrenaline

Animals need to recover quickly after feed and water deprivation in order to maintain the efficiency of production or ensure meat quality.

There is species and individual responses to feed and water deprivation. Sheep do better than cattle. Young animals, deer in winter and stock exposed to feed and water deprivation in the morning.

Iron Metabolism —

There is a brilliant review of iron metabolism and the implications for deficiency in the Lancet

Zimmermann and Hurrell Nutritional iron deficiency 2007 Lancet 370, 511-20

Estimates of iron deficiency in developed countries are usually derived from specific indicators of iron status. These are expensive so in developing countries estimates are often based on haemoglobin alone which does not allow for other causes of anaemia , eg vitamin A deficiency), infectious disorders (particularly malaria, HIV disease, and tuberculosis), haemoglobinopathies, and ethnic differences in normal haemoglobin distributions.

WHO estimates that 39% of children younger than 5 years, 48% of children between 5 and 14 years, 42% of all women, and 52% of pregnant women in developing countries are anaemic, with half having iron deficiency anaemia. Iron deficiency is also common in women and young children in industrialised countries. In the UK, 21% of female teenagers between 11 and 18 years, and 18% of women between 16 and 64 years are iron deficient. Other countries have similar figures.

Human beings are unable to excrete iron actively, so its concentration in the body must be regulated at the site of iron absorption in the proximal small intestine. Diets contain haem and non-haem (inorganic) iron; each form has specific transporters. There is an intestinal haem iron transporter which is upregulated by iron deficiency, which may also transport folate. Transport of non-haem iron from the intestinal lumen into the enterocytes is mediated by the divalent metal ion transporter 1 which transports only ferrous iron, but most dietary iron that enters the duodenum is in the ferric form. Therefore, ferric iron must be first reduced to ferrous iron, possibly by the brush border ferric reductase, duodenal cytochrome b or by other reducing agents, eg ascorbic acid. Inside the enterocyte, iron may be stored as ferritin or crosses the basolateral membrane into the blood, controlled by the transport protein ferroportin 1, and the iron oxidase, hephaestin.

When red cell are old they are broken down in the spleen and the freed iron binds to transferrin, which binds to transferrin receptors in the bone marrow and this iron is incorporated into new red cells.

Within cells, iron status upregulates or downregulates ferritin and transferring receptors important in iron homeostasis by binding at the post-transcription level iron regulatory proteins to specific non-coding sequences in their mRNAs, called iron-responsive elements. Various genes are modulated by iron status, many of these genes are not directly related to iron metabolism.

During gestation, the fetus stores about 250 mg of iron which is used during breastfeeding, as breastmilk supplies only about 0-15 mg of absorbed iron per day, whereas requirements for absorbed iron are about 0-55 mg per day. Low birth weight infants do not store sufficient iron and are at risk of developing iron deficiency while being breastfed. During growth in childhood, about 0-5 mg of iron per day is absorbed in excess of body losses; adequate amounts of iron during growth typically results in a 70-kg man accumulating about 4 g of body iron. About 2-3 g of body iron is within haemoglobin and about 1 g is stored as ferritin or haemosiderin, mainly in the liver. Men absorb and excrete about 0-8 mg of iron per day, and women, during childbearing years, should absorb almost twice as much (1 -4mg per day) to cover menstrual losses. The usual diet of a population strongly affects iron bioavailabiiity,so that recommended intakes for iron depend on diet characteristics.

Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations eating plant-based diets with little meat. In meat, 30-70% of iron is haem iron, 15-35% of which is absorbed. However, in plant-based diets most dietary iron is non-haem iron, and its absorption is often less than 10%. The absorption of non-haem iron is increased by meat and ascorbic acid, but inhibited by phytates, polyphenols, and calcium.The needs for iron increase in infants and young children, adolescents, and in menstruating and pregnant women.

Increased blood loss from gastrointestinal parasites aggravates dietary deficiencies in many developing countries.

During the first two trimesters of pregnancy, iron deficiency anaemia increases the risk for preterm labour, low birthweight, infant mortality, and predicts iron deficiency in infants after 4 months of age. Data for the adverse effects of iron deficiency on cognitive and motor development in children are equivocal because environmental factors limit their interpretation


There are three main strategies for correcting iron deficiency in populations, alone or in combination: education combined with dietary modification or diversification, or both, to improve iron intake and bioavailability; iron supplementation (provision of iron, usually in higher doses, without food); and iron fortification of foods. A new approach is biofortification through plant breeding or genetic engineering. Although dietary modification and diversification is the easiest , changing dietary practices and preferences is difficult, and foods that provide highly bioavailable iron (such as meat) are expensive.

For oral supplementation, ferrous iron salts (ferrous sulphate and ferrous gluconate) are preferred as they are cheap and have high bioavailability. Standard therapy for iron deficiency anaemia in adults is a 300-mg tablet of ferrous sulphate (60 mg of iron) three or four times per day.

Iron fortification is probably the most practical, sustainable, and cost-effective long-term solution to control iron deficiency at the national level. Fortification of foods with iron is more difficult than it is with other nutrients, such as iodine in salt and vitamin A in cooking oil. The most bioavailable iron compounds are soluble in water or diluted acid, but often react with other food components to cause flavour, and colour changes, fat oxidation, or both. Thus, less soluble forms of iron, although less well absorbed, are often chosen for fortification to avoid unwanted sensory changes.

Knut Schmidt-Nielson 1915-2007 —

Knut Schmidt-Nielsen, one of the all-time greats of animal physiology, died on 25 January 2007 aged 92..

He studied life in deserts, where heat and drought makes survival difficult. The most effective means of keeping cool depend on evaporation of precious water, either in the breath or as sweat, but kangaroo rats survive in the Arizona Desert with nothing at all to drink. They keep reasonably cool by spending the day in burrows and emerging only at night. But even at night they would lose much too much water in their breath if it were not for their remarkable noses. The air they breathe in is relatively cool and dry, but it is inevitably warmed in the body and becomes saturated with water vapour. To minimize water loss, this air must be cooled before it leaves the body to condense out most of the vapour. Schmidt-Nielsen showed that the incoming air cools the surfaces of the nasal cavity, which, in turn, cools the air when it is breathed out again. He showed that the same principle operates in other mammals and birds, but is particularly effective in kangaroo rats because their nasal surfaces are enlarged by elaborate nasal bones the turbinals. They also save water by producing exceptionally con concentrated urine.

In contrast dogs overheated by exercise, need to let water evaporate to cool themselves. With colleagues, Schmidt-Nielsen showed that panting dogs avoid the effect by breathing in through the nose but out through the mouth.

Camels are too big to shelter in burrows in the heat of the day. Schmidt-Nielsen showed that camels avoid the water loss by allowing their bodies to heat up by day and cool by night. A camel may start the morning with a body temperature of only 34°C, but warms to 41°C during the afternoon. This strategy would be ineffective for small animals such as kangaroo rats, because they would quickly heat up to lethal temperatures. Schmidt-Nielsen then showed that camels’ noses also effectively conserve water .

Sea birds face a different problem: they drink sea water, which has a much higher osmotic concentration than their blood. Instead of producing urine even more concentrated than sea water, they have glands opening into their nostrils which secrete droplets of concentrated salt solution that are shed by a shake of the head.

In the later part of his career, Schmidt-Nielsen studies the energy budgets of animals with other. They measured the rates of oxygen consumption of various mammals, ranging from mice to horses, running at different speeds. They calculated the quantity of oxygen used per kilogram of animal moving a distance of one metre, this was less for large animals than small. Implying that the muscles of small animals are less efficient.

Similar relationship of oxygen consumption and body mass was shown for flying birds and swimming fish. Flight is cheaper than running (for the same body mass), and swimming is cheaper still.

Obituary in Nature Alexander Nature 2007, vol 446, p 744

RDI Of Trace Elements —

There is a good review of methods of evaluating the status of trace elements in the body for Nutrition

Ed Fairweather-Tait and Harvey

Micronutrients status methods Proceedings of the EURRECA Workshop and working party on new approaches for measuring micronutrient status.

BJN vol 99 Supplement 3 pp S1-80

Biomarkers of copper status: a brief update

Harvey and McArdle

Copper (Cu) deficiency in humans is associated with anaemia, hypercholes-terolaemia and bone malformations. Despite significant effort over several decades a sensitive and specific Cu status biomarker has yet to be identified.

Current biomarkers include a range of cuproenzymes such as the acute phase protein caeruloplasmin and Cu-Zn-super-oxide dismutase all of which are influenced by a range of other dietary and environmental factors. A recent development is the identification of’ the Cu chaperone, CCS as a potential biomarker; although its reliability has yet to be established.

Merhods to assess iron and iodine status


Four methods are recommended for assessment of iodine nutrition: urinary iodine concentration, 1 the goitre rate, and blood concentrations of thyroid stimulating hormone and thyroglobulin. These indicators are complementary, in that urinary iodine is a sensitive indicator of recent iodine intake (days) and thyroglobulin shows an intermediate response (weeks to months), whereas changes in the goitre rate reflect long-term iodine nutrition (months to years). Spot urinary iodine concentrations are highly variable from day-to-day and should not be used to classify iodine status of individuals. International reference, criteria for thyroid volume in children have recently been published and can be used for identifying even small goitres using thyroid ultrasound. Recent development of a dried blood spot thyroglobulin assay makes sample collection practical even in remote areas.

Serum ferritin remains the best indicator of iron stores in the absence of inflammation. Measures of iron-deficient erythropoiesis include transferrin iron saturation and erythrocyte zinc protopor-phyrin, but these often do not distinguish anaemia due to iron deficiency from the anaemia of chronic disease. The serum transferrin receptor is useful in this setting, but the assay requires standardization. In the absence of inflammation, a sensitive method to assess iron status is to combine the use of serum ferritin as a measure of iron stores and the serum transferrin receptor as a measure of tissue iron deficiency.

Update on the assessment of magnesium statue


There is no simple rapid and accurate method, only serum magnesium and use of loading dosage methods.

Indicators of zinc status at the p[population level: a review of the evidence.

Gibson, Hess, Hotz, Brown

There are few reliable methods, only serum zinc and the clinical sign of clinical runting in children. of


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