Scientific discoveries and chance.

Whilst careful logic applied to science is the hall mark of science, observation and chance also play a significant in new discoveries.
When Jenner listened to the milk maid talking about the protective abilities of cow pox against small pox a new era entered social medicine. Similarly Withering responded to an account of the therapeutic benefits of digitalis in heart failure , an infusion from the fox glove flower.
The clue is the listening and then testing.
Chance is Fleming who was studying the ability of tear drops to inhibit the growth of bacteria seeing by chance that a penicillin fungal infection killed bacteria growing on the same agar plate.
The time interval used for many dietary fibre studies is three weeks, the reason for this being that in the first experiment on bran three weeks was chosen because the experiment could then be finished between the Edinburgh Medical Faculty Ball and Christmas.
The subsequent promotion of the idea and observation must then be subjected to careful scientific studies and abandoned if the experiments don’t fit the inspired thought.
Such was the discovery of the tranquilliser drug largactil. This drug met theoretical requirements of an ideal drug. When tested in all organ tests it was without effect. So in exasperation one of the scientists who was quite agitated drank the potion and felt very calm. A new drug was found.

Water supplies and conservation

Water is vital to life The American Museum of Natural History has an exhibition on Water ( Water : H2O = Life.)
The exhibition shows the difference in usage in different parts of the world. The average North American, uses between 227 and 340 litres of water per day. Yet Atlanta, Georgia, will run out of drinking water within the next four months if it doesn’t rain soon. The city is experiencing its driest year since 1931. In some parts of sub-Saharan Africa, women spend between 15 and 17 hours a week collecting water..
20 litres per day is the minimum amount of clean water required to meet basic human needs, drinking, cooking and hygiene. Some people in parched places have to survive on just 5 litres or less. One quarter of Mexico City’s residents have no access to tap water; others have only 1 hour a week.
The exhibit’s emphasis is on water conservation. It takes 3 litres of water to produce a 1-litre bottle of bottled water .
There are innovative methods to extract, conserve and purify water. More than 700 PlayPump water systems have been installed in rural South Africa and other sub-Saharan countries. Children spinning on these colourful merry-go-rounds 16 times per minute generate enough energy to pump about 1,400 litres of water per hour from boreholes 40 metres deep. Perth , Australia gets 20% of its water supply from the Indian Ocean, desalinated with wind power. Windhoek in Namibia reclaims up to 30% of its water from sewage.
Bangladeshi women have cut cholera incidence in half using sari fabric, folded eight times, to filter bacteria from water.
Following the writings of Snow and the demonstration in the late 19th century that faecal contaminated water was a factor in the spread of cholera the London Corporation built separate water mains and sewerage tunnels emptying downstream into the Thames river, a system that is still in use. The Thames and Lee rivers now supply drinking water to 8.3 million residents in th London area every day.
Systems age and the antiquated system allows hundreds of millions of litres of untreated sewage to pass directly back into the rivers . This happens in London and in the River Forth in front of my house. .
Glausiusz J (2007) The liquid of life Nature vol 450 p 353

Gene control and retinoic acid

In cells genes are turned off or on according to the requirements and type of cell. Clearly an intestinal cell will behave differently to a nerve cell yet arising from the same germinal cell line. Yet the genes are the same.
The silencing of genes can be controlled by the Polycomb group of proteins. These alter the structure of chromatin the DNA – histone complex. Such silencing may be thorough the addition of specific small molecular weight molecules to the histone. This can be reversible.
The manner in which genes are arrayed within the cell determines transcription. The suppressing tags include acetyl, methyl and phosphate groups added to specific amino acids in histones. Methylation is the most stable addition and be retained through many life cycles. There are histone demethylase enzymes which remove the methyl additions to the histone.
A newly described demethylase enzyme acts with a retinoic acid receptor to prevent expression of retinoic acid responsive genes. Retinoic acid can signal to the Polycomb group proteins to remove histone tags in nerve cell releasing more specialised stem cells. Retinoic acid also has a role in bone marrow and macrophage gene unlocking .
Jones (2007) Reversing the irreversible Nature vol 450 pp 357-9

Stem cells and medical usage

Several fines of evidence have suggested extensive proliferaton activity and pluripotency of germline stem cells, including spermatogonial stem cells .
In an early embryo a cell has the potential to generate many different cell types. During development cells generally lose this potential or ’potency’, and become restricted to making one or a few cell types. Cells can become undetermined and undifferentiated in special circumstances. These Undifferentiated cells which are capable of self-renewal and differentiation into more specialised cells are called stem cells . . Stem cells have the potential to develop into many different cell types in the body They might act as a repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or » brain cell.
Karin Nayernia ( 2007 : Stem cell derived from testis show promise for treating a wide variety of medical condition’ Cell Research 17, 895-897 )
Has written a review showing the possibility of using the continued presence of stem cells in the testis for the repair of medical problems. The maturation of such stem cells may well have needs for nutritional support in as yet unsuspected ways.

Useful UK websites

Food Standards Agency www.food.gov.uk
www.food.gov.uk/eatwell.gov.uk
www.salt.gov.uk

Statistics UK www.statistics.gov.uk

Defra UK www.defra.gov.uk

Allergy www.food.gov.uk/safereating/allergyintol

Allergy UK www.allergyuk.org

British Heart Foundation www.bhf.org.uk

www.heartstats.org

Cancer www.cancerresearchuk.org

Diabetes www.diabetes.org.uk

Age related macular degeneration and anti-oxidants

Early age related macular degeneration is characterised clinically by yellow deposits known as drusen and changes in pigmentation of the retina. Late age related macular degeneration develops when there is a growth of new blood vessels that bleed into the subretina] space or when the macula atrophies. Both conditions usually lead to severe loss of central vision. The pathogenesis of age related macular degeneration is unclear, older age, genetic markers, and cigarette smoking are the only reported risk factors. Treatment options are few and not very helpful.
Dietary antioxidants have long been suggested as useful for preventing the development and progression of AMD. The retina, with its high oxygen content and constant exposure to light, is particularly susceptible to oxidative damage
Evidence of the role of dietary antioxidants as a primary preventive measure for age related macular degeneration is not conclusive. Some studies, but not others, suggest that diets rich in anti-oxidants may protect against the development of signs of early age related macular degeneration . Chong and colleagues have published a systematic review and meta-analysis of the role of a range of dietary antioxidants in the primary prevention of age related macular degeneration.
The conclusions of this major survey was that there was insufficient evidence to support the use of dietary anti oxidant supplements for the primary prevention of early age related macular degeneration
Chong et al 2007 Dietary anti oxidants and primary prevention of age related macular degeneration : systematic review and meta-analysis . BMJ vol 335, 755-9

Prolonged fatigue and workout

This is not nutrition but is of interest, at least to me.
Burnout and prolonged fatigue are both characterised by the symptom of fatigue. Both come from different backgrounds. Prolonged fatigue has a medical cause. Burnout has a psychological origin eg work conditions .
There is considerable overlap between the two conditions. However burnout is seen as not merely fatigue bu rather a specific work related syndrome.
Leone et al 2007 Similarities , overlap and differences between burnout and prolonged fatigue in the working population QJM vol 100 , 617-627

Prolonged fatigue and workout

This is not nutrition but is of interest, at least to me.
Burnout and prolonged fatigue are both characterised by the symptom of fatigue. Both come from different backgrounds. Prolonged fatigue has a medical cause. Burnout has a psychological origin eg work conditions .
There is considerable overlap between the two conditions. However burnout is seen as not merely fatigue bu rather a specific work related syndrome.
Leone et al 2007 Similarities , overlap and differences between burnout and prolonged fatigue in the working population QJM vol 100 , 617-627

Obesity education in schools

There have been a number of obesity prevention schemes for children in schools. The reasonable premise is the young are receptive and they have a life ahead to be influenced
A Cochrane report found that in 27 intervention schemes success was meagre. Possibly because they were too short term
An intervention scheme in the South of England concentrated on carbonated drinks and health talks. The results were encouraging at 12 months. However at 3 years the benefit had disappeared. Suggesting that there can be no let up in the programme.
One third of the children were lost to follow up.
This is a life long project
James et al 2007 Preventing childhood obesity: two year follow-up results from the Christchurch obesity prevention programme in schools (CHOPPS) BMJ vol 335 pp 762-764

Maths and the dynamics of cancer

An old question is not why do we go to sleep but why do we wake up again ?
Similarly multicellular creatures are made of an array of different cellular structures all of which are dividing and developing until death for whatever reason.
One cause of death which is feared is cancer. To some extent the puzzle is not that cancer develops but that normal physiological growth, tissue formation and preservation is the norm. For cancer to develop a sequence of events must occur and a series of defence or constraining processes overcome.
The mathematician is a brave person who through formulae, assumptions and no constraints of laboratory data can tackle the problems of biological processes. These modelling arguments are very important if not sometimes difficult to follow. The popular problem to tackle is the cancer process.
Weinberg reviews a new book on the dynamics of cancer by Steven Frank which grapples with this interesting approach to as yet an unresolved problem.
Weinberg (2007 ) Using maths to tackle cancer Nature vol 449, 978-81
Frank Dynamics of Cancer : Incidence, inheritance and evolution . Princeton University Press .

Group living and animal nutrition

A popular programme on TV is nature films showing lions, cheetahs , whales and sharks killing their food. Very dramatic and for some beats going round Tesco to buy the weeks food.
The assumption has always been that the predators gain by hunting in packs by being able to tackle larger prey.
The truth may not be a simple as this. Animal s hunting on their own in the short term eat better. Group living influences individual food intake rates and the dynamics of the populations of predators and their prey. The grouping of prey and predators reduces the amount that each individual predator eats. The group allows a larger area to be swept looking for prey, and allows the area to be defended from interloper groups.
What parallels this has in human nutrition I cannot immediately say, but eating together rather than on ones own can only be better.
Fryxell et al (2007) Nature vol 449, 1041-1043
Coulson (2007 ) Group living and hungry lions Nature vol 449 996-7

Synergy in nutrition

One of the great discoveries in Nutrition was that of Justus von Liebig in the 19th century. He showed that crop production is limited by the nutrient in shortest supply. His law of the minimum.
Plants require carbon, hydrogen and oxygen from atmospheric gases and water. And of course trace elements.
The work of Liebig has transformed agriculture and taken some of the worry of Malthus and his theory of population from us, at least for a while.
The ready provision of food has enabled the human population to grow in an unfettered manner. However the excess of nitrates and phosphorous added to the land and the seepage into the overall system especially water has had dire consequences. Including a proliferation of algal bloom. This has had consequences for fish stock and available oxygen in the water.
Elser and colleagues in Ecology Letters have made a meta analysis of the effects of these two elements on the biomass. The effect of adding nitrogen and phosphorous to growing plants is profound. At the same time there is a synergistic effect and both are required. The effect is to alter complex metabolic relationships within the plant which have yet to be fully understood
Nevertheless we have here an important nutritional point of relevance to human nutrition. There are limiting elements in our diet.
The concept of a balanced diet is not a platitude but central to good nutrition.
Davidson and Howarth 2007 Nutrients in synergy Nature vol 449, 1000-1001

Carbohydrates in Human Nutrition

The European Journal of Clinical Nutrition 2007 vol 61 has published a supplement. S1-137
Joint FAO/ WHO scientific update on carbohydrates in human nutrition
INTRODUCTION
FAO / WHO Scientific Update on carbohydrates in human nutrition: introduction
C Nishida & F Martinez Nocito
REVIEWS
Carbohydrate terminology and classification
J H Cummings & A M Stephen
Nutritional characterization and measurement of dietary carbohydrates
K N Englyst, S Liu & H N Englyst
Physiological aspects of energy metabolism and gastrointestinal effects of carbohydrates
M Elia & 3 H Cummings
Carbohydrate intake and obesity
R M van Dam & J C Seidell
Dietary carbohydrate: relationship to cardiovascular disease and disorders of carbohydrate metabolism
J Mann
Carbohydrates and cancer: an overview of the epidemiological evidence
T J Key & E A Spencer
Glycemic index and glycemic load: measurement issues and their effect on diet-disease relationships
B J Venn & T J Green

FAO/WHO Scientific Update on carbohydrates in human nutrition: conclusions
J Mann, J H Cummings, et al

Sanitation a pre-requisite for health

Our interest in food may not to stop once the residue leaves the colon into the outside world.
In Asia, Africa and Latin America more than two and half billion people ( 40% of the worlds population) have no toilets with a proper waste removal system. In India the figure is 700 million. In Afghanistan less than 10% have access to toilets. Which is a major source of disease, as the free expression leads to contamination of drinking water and the spread of highly lethal diseases e.g. cholera with faecal contamination ( in 2006 over 230,000 reported cases ) and hepatitis from faecal and urinary contamination. When there is a serious sanitation programme then the death rate particularly in children falls . There are cultural problems and the need or education, to use toilets and for them to be kept clean and healthy. My wife and I have a league of the worst toilet we have seen , one in South Mexico is a slender winner.
It also must be said what a remarkable system the urban sewage system is. The pioneering London scheme in the Victorian era and the development of similar systems in the cities, town, villages has transformed life and health.
Leader Lancet 2007 Access to toilet for all Lancet vol 370, p 1590
Durrheim 2007, A clarion call for greater investment in global sanitation Lancet vo370, 1592-3
Barreta et al 2007 Effect of city-wide sanitation programme on education in rate of childhood diarrhoea in northeast Brazil : assessment by two cohort studies Lancet ; vol 370, 1622-28

betaine, homocysteine and cognitive function in the elderly

One-carbon metabolites choline and homocysteine.are important for brain function. The relationship between the one-carbon metabolites choline. betaine. methionine and dimethylglycinc with cognition in elderly has been looked at by Simone et al in a population of elderly Dutch people as a double-blind, placebo-controlled trial.
Individuals (n 195) were randomized to receive daily oral capsules with either 1000ug cobalamin (vitamin B12), or 1000ug cobalamin and 400 ug folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycinc were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment.
At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed.
Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36%. and increased betaine concentrations by 38%. Participants with the largest increases in betaine concentrations showed a borderline significant (P=0-07) higher memory performance compared to those without it.
Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function.
In short a brave, very detailed attempt but no rewards to any one.
Simone et al (2007) The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people British Journal of Nutrition 98, 960-968

Vitamin A supplementation dosage

Vitamin A supplementation
Vitamin A deficiency is a worldwide nutritional problem. The well being of millions of babies and infants and mothers are threatened by this deficiency ( calculated to be 127 million ) and 7 million pregnant women. .
Most developing countries provide vitamin A supplements to infants and new mothers according to WHO recommendations. However, in 2002, the International Vitamin A Consultative Group recommended a higher dose of vitamin A. Momodou Darboe and colleagues ( Darboe et al 2007, effectiveness of an early supplementation scheme of high-dose vitamin A versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial designed a randomised controlled trial Lancet vol 369 pp 2088-96 ) ( 25000 IU v three doses of 50000 IU) to assess both dosing regimens.
No significant differences were noted for primary outcomes—
maternal vitamin A concentration at 2 months;
infant vitamin A at 5 months;
H pylori infection at 12 months;
maternal pneumococcal carriage at 12 months;
infant pneumococcal carriage at 12 months;
and infant gut mucosal damage at 12 months.
The investigators concluded that they saw no additional benefits of the high-dose regimen and recommend that the WHO regimen should not be changed.
In a Comment, Bernard Brabin Lancet 2007 Infant vitamin A supplementation : consensus and controversy pp 2054-56) discusses the controversy surrounding the selection of the optimum dose. The higher dosage raises concerns about overdosage.

dietary microparticles and intestinal response

Dietary microparticles and their impact on tolerance and immune responsiveness of the gastrointestinal tract
Powell et al (2007 ) British Journal Nutrition Dietary microparticles and their impact on tolerance and immune responsivenes of the gastrointestinal tract. vol 98, supplement S59-63
This is an interesting and novel approach and an important contribution to a theory for the aetiology of Crohn’s disease. Crohn’s disease is said to be a new condition. Who knows? One theory was that toothpaste and other sources of indigestible particles is a factor. So the authors have reviewed the evidence.
Dietary microparticles are non-biological bacterial-sized particles of the gastrointestinal lumen that occur due to endogenous formation (calcium phosphate) or following oral exposure (exogenous microparticlc). In the UK. about 40 mg (10 x12) of exogenous microparticles are ingested per person per day, through exposure to food additives, pharmaceutical/supplement excipients or toothpaste constituents.
Once ingested, exogenous micro particles are unlikely to pass through the gastrointestinal tract without adsorbing to their surfaces some ions and molecules of the intestinal lumen. Both entropy and ionic attraction drive such interactions. Calcium ions are especially well adsorbed by dietary micro particles which then provide a positively charged surface for the attraction (adsorption) of other organic molecules such as lipopolysaccharides, peptidoglycans or protein antigen from the diet or commensal flora.
The major (but not only) sites of microparticle entry into intestinal tissue arc the M-cell rich lymphoid aggregates (termed Peyer’s patches in the small bowel). Indeed, it is well established that this is an efficient transport route for non-biological microparticles although it is unclear why.
The authors suggest that this pathway exists for “endogenous microparticles” of calcium phosphate. with immunological and physiological benefit, and that “exogenous dietary microparticles”, such as titanium dioxide and the silicates, hijack this route.
This overview focuses on what is known of these microparticles and outlines their potential rule in immune tolerance of the gut (endogenous microparticlesl or immune activation (exogenous microparticles) and inflammation of the gut.

Immuno nutrition review

A supplement to the October 2007 British Journal of Nutrition; vol 98, supplement 1 is devoted to immuno nutrition in Health and disease. This is a tour de force. A brilliant example of modern scientific nutrition at its very best.
There are four introductory reviews including the recent history of the science.
The improvements in nutrition consequent upon the improved knowledge of what matters in nutrition is described by Scrimshaw and Solomon, who have achieved so much in this field.
The benefits of better nutrition and supplements of vitamins( vitamins A, D, E, C, B6, B12 ) and trace elements( iron, copper, selenium, zinc ) are major advances in Health and disease reduction
There are papers on the immune system and micronutrients, fatty acids and bioactive compounds ,and alcohol. The inflammatory process and obesity. Finally the important area of immuno nutrition and illness.
The President and vice President of the Work shop modestly call the publication excellent overview, an understatement.

tea bag colour and taste.

Have you noticed that when one makes a cup of tea with a tea bag, 90% of the colour leaches into the water in 1 minute and only 10% of the taste.

Joan Eardley pictures and Glasgow children stature1950s

When I came to Edinburgh in 1954 and arrived on the overnight train I was struck by the small stature of the workmen in Princes Street. This is no longer the case.
There is a wonderful exhibition of paintings by Joan Eardley in the Scottish Gallery at the bottom of the Mound. . In addition to her masterly sea and landscapes there are paintings of Glasgow children after the 2nd world war. Despite the improved nutrition with rationing and a more equitable distribution of food they are still very underweight. The fat boy, there always was a fat boy would be at the most plump in modern day parlance.

Intestinal stem cells

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. The absorptive epithelium of

the small intestine is ordered into crypts and villi, which in the mouse turn over every three to five days. The

rapid rate of ceil production in the crypts is balanced by apoptosis at the tips of the villi.

Self-renewing stem cells cycle steadily to produce the cells capable of differentiating towards all types of

intestinal cells. . The estimated number of stem cells is between four and six per crypt:. Long-term DNA-

label retention has tentatively located stem cells directly above the Paneth cells’. Three differentiated cell

types (enterocytes, goblet cells and enteroendocrine cells) form from trans it-amplifying cells at the crypt-

villus junction and continue their migration in coherent bands stretching along the crypt-villus axis. Each villus

receives cells from multiple different crypts. The fourth principal differentiated cell type, the Paneth cell,

is at bottom of the crypt

The colon epithelium contains crypts, but has a flat surface rather than carrying villi. This epithelium

consists of two main differentiated cell types: the absorptive colonocytes and the goblet cells’. Until now, no

stem cells have been identified in the colon.

Using an intestinal target gene Lgr5 Barker et al have demonstrated that the crypt base columnar cell generated all

epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon.

Barker et al. ( 2007 ) Identification of stem cells in small intestine and colon by marker gene Lgr5 Nature vol 449,

1003-7

Sleeping metabolic rate

Methodology papers are so important.
Basal Metabolic Rate, is measured at complete rest and without physical work ( basal metabolism . This is the energy required for the activity of internal organs and to maintain body temperature. This contributes some 60-70% of Total Energy Expenditure. It is said that during sleep the overall metabolism approximates to the basal metabolic rate. Ganpule et al ( European Journal of Clinical Nutrition : Inter individual variability in sleeping metabolic rate in Japanese subjects. , [ 2007] vol 61, 1256-1261) show that the sleeping metabolic rate has a smaller prediction error than basal metabolic rate and is a more accurate value.
I wonder what effect the REM ( rapid eye movement phase of sleep has on the measurement?

World cancer research fund recommendations for diet, activity and cancer prevention

Amid substantial publicity the World Cancer Research Fund has published its report on cancer, physical activity and diet
http://www.wcrf-uk.org/.
The overall recommendations are 10 in number, of which the first 7 are the general ones.
It would be interesting to know how these recommendations fit with the large pool of knowledge on the molecular biology of cancer which now exists and is being added to. Shades of Mr Casaubon in George Elliot’s novel Middlemarch.

1. Be as lean as possible without becoming underweight
Convincing evidence shows that weight gain and obesity increases the risk of a number of cancers, including bowel and breast cancer. Maintain a healthy weight through a balanced diet and regular physical activity to help keep your risk lower.
2. Be physically active for at least 30 minutes every day
There is strong evidence that physical activity protects against cancers including bowel and breast cancer. Being physically active is also key to maintaining a healthy weight. .Any type of activity counts-the more you do the better! Try to build some into your everyday fife.
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3. Avoid sugary drinks. Limit consumption of energy-dense foods and drinks (particularly processed foods high in added sugar, or low in fibre, or high in fat. Try to eat lower energy-dense foods such as vegetables, fruits and wholegrains instead. Opt for water or unsweetened tea or coffee in place of sugary drinks.
4. Eat more of a variety of vegetables, fruits, wholegrains and pulses such as beans. . As well as eating your 5 A DAY, try to include wholegrains (e.g. brown rice, wholemeal bread and pasta) and/or pulses with every meal.
5. Limit consumption of red meats (such as beef, pork and lamb) and avoid processed meats
6. If consumed at all. limit alcoholic drinks to 2 for men and 1 for women a day
7. Limit consumption of salty foods and food processed with salt (sodium)

8. Don"t use supplements to protect against cancer
Research shows that high-dose nutrient supplements can affect our risk of cancer, so it's best to opt for a balanced diet without supplements.

Food additives and hyperactivity behaviour

It has been claimed , originally by Ben Feingold more than 30 years ago that artificial food colours and other food additives affect behaviour in children.
The principle effect of artificial food colours and other food additives is said to cause overactive, impulsive, and inattentive behaviour, i.e. hyperactivity. A pattern of behaviour that has substantial individual differences in the general population. Children who show this behaviour pattern to a large degree can be diagnosed with attention-deficit hyperactivity disorder (ADHD). A recent meta-analysis of double-blinded, placebo-controlled trials has shown a significant effect of artificial food colours and other food additives on the behaviour of children with ADHD. The possible benefit in a reduction in the level of hyperactivity of the general population by the removal of AFCA from the diet is less well established.
A community-based, double-blinded, placebo-controlled food challenge described in a paper in the Lancet tested whether the intake of artificial food colour and additives affected childhood behaviour.
In this trial 3-year-old and 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two mixes (A or B) or a placebo mix.
Mix A included artificial food colouring, sunset yellow [E110], carmoisine [E122], tartrazine [E102], and ponceau 4R [E124 ] and sodium benzoate [E211].
Active mix B included artificial food colourings (sunset yellow, carmoisine, quinoline yellow [E110], and allura red AC E129j) and sodium benzoate.
The dosage for 3 year olds was equivalent to eating two 56 g bags of sweets a day, and for 8/9 years old dosage of A equivalent to 2 Bags of sweets and B 4 bags of sweets.
The main outcome measure was a global hyperactivity aggregate, based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention.
Mix A had a significant adverse effect compared with placebo in global hyperactivity aggregate for all 3-year-old children but not mix B versus placebo. 8/9-year-old children showed a significantly adverse effect when given mix A or mix B
The authors concluded that artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population. There were significant individual differences in response to these compounds
It is important to note that sodium benzoate is an important food preservative whereas the other substances are cosmetic.
Eigenmann and Haenggeli 2007 Food colourings, preservatives and hyperactivity The Lancet vol 370, 1524-5
McCann et al (2007) Food additives and hyper active behaviour in 3 year old and 8/9 year old children in the community: a randomised double-blinded, placebo-controlled trial Lancet vol 370, 1560-67

Obesity in a woman's life

Ryan explains the disadvantages of obesity with in a stark list of outcomes at every stage of life ( Ryan 2007 Obesity in women: a life cycle of medical risk: International Journal of Obesity , 31, S3-S7.
Obesity can have an adverse affect at each stage of a woman’s life cycle.
In young women, obesity has an impact on psycho social health and, as they grow older and become parents, on their reproductive health. Obesity is also associated with a number of serious risks during pregnancy.
In older women , obesity is associated with a number of chronic diseases. E.g. type 2 diabetes and cardiovascular disease, and possibly increased risk for almost all types of cancer.
The elderly obese woman, should she live that long is at risk for dementia and Alzheimer’s disease.
Obesity has a marked impact on life expectancy.
The medical risks associated with obesity in women are also important for the woman’s children and future generations.
There is emerging evidence that nutrition during foetal and early life can influence risk for obesity and chronic diseases for both sexes.

Obesity and genes

Adipose-tissue contains the largest store of energy in the body and has important roles in regulating energy partitioning. Adipose tissue is also seen as an active biological tissue rather than a mass of fat.
Developments in genomics, in particular microarray-based expression profiling have: provided scientists with a number of new candidate genes whose expression in adipose tissue is regulated by obesity- Integrating expression profiles with genome-wide linkage and/or association analyses is a promising strategy to identify new genes underlying susceptibility to obesity.
An article by Dahlman and Arner gives a comprehensive review of adipose-tissue expressed genes possibly involved in predisposition to human obesity
The following genes are of potential note.
peroxisome proliferator-activated receptor gamma
INSIG2 acting in adipogenesis;
the adrenoreceptors beta 2 and 3,
hormone-sensitive lipase acting on lipolysis:
uncoupling protein a acting in mitochondria energy expenditure ;
and among secreted molecules the cytokine tumor necrosis factor alpha and the hormone leptin.
Whilst this is in part inspired speculation, the concept of predisposition is an interesting thought. But obesity is the result of an imbalance between food intake and energy expenditure resulting in the storage of energy as fat. No food, no obesity. Or is that the case?
Dahlman and Arner 2007, Obesity and polymorphisms in genes regulating human adipose tissue. International Journal of Obesity vol 31, 1629-1641

weight history and physical performance.

Are overweight individuals overweight all their lives ? We have all seen pictures of lean and hungry looking youngsters and this contrasts with the overweight middle age person. I have always related this to less exercise and an ample diet and alcohol intake in the more sedentary older person.
Houston et al (2007 ) The association between weight history and physical performance in the Health , ageing and body composition study : International Journal of Obesity vol 31, 1680-1687.show just that.
Maintaining a healthy body weight throughout adult life may play a role in preventing or delaying the onset of less physical activity
A thought on this is in my experience (small though this is ) that long distance athletes ( slow muscle predominantly ) tend to keep exercising throughout life whereas the sprinters Fast muscle predominantly ) retire form exercise early on and become overweight. An interesting field for study.

hand grip strength and nutrition screening

The identification of patients coming to hospital as being under or over weight is very important. Especially the underweight.
There are many methods and Body Mass Index is the hall mark measure.
Matos et al write in EJCN that handgrip strength is a good indicator of underweight patients.
This is an easy method in principle and fun if a happy person teases the patient into a good test.
However the test may be compromised by arthritis, strokes, anxiety ( not another bloody test ) and inattention
My own feeling is look at the person are they thin, fat or normal size?
Matos LC et al (2007) handgrip strength as a hospital admission nutrition risk screening method. European Journal Clinical Nutrition vol 61, 1128-35.

Stem cell differentiation control

This is not easy stuff ,but if read slowly drinking a cup of tea ,can be at the very least comprehended. Again a complex system controlled by a methylation process.
The stem cell complex is capable of differentiating into most if not all tissues. The differentiation is determined by histone modification . Histones are the protein wrapping around the DNA.
Bone and fat are somewhat different and their formation involves osteoblasts and adipocytes respectively. The production of osteoblasts and adipocytes from common mesenchymal stem cells is under transcriptional control. Peroxisome proliferator receptor-γ is an marrow . inducer of fat tissue formation
Takada and colleagues have shown that a pathway using CaMKII-TAKl-TAB2-NLK transcriptionally represses PPAR-γ transactivation and induces Runx2 expression, promoting osteoblastogenesis in preference to adipogenesis in bone marrow mesenchymal progenitors. Wnt-5a activates NLK (Nemo-like kinase), which in turn phosphorylates a histone methyltransferase, SETDB1 (SET domain bifurcated 1), leading to the formation of a co-repressor complex that inactivates PPAR-γ function through histone H3-K9 methylation. The signalling pathway suppresses PPAR-γ function through chromatin inactivation triggered by recruitment of a repressing histone methyl transferase, thus leading to an osteobtastic cell lineage from mesenchymal stem cells.
Takarda et al 2007 A histone lysine methyltransferase activated by a non-canonical Wnt signalling suppresses PPAR-γ trans activation. .Nature Cell Biology 9, 1273-1285
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Organism and organ size control

Organism and organ size control
The control of organ (or organism) size is a fundamental aspect of life ? What makes an elephant grow a million times larger than a mouse? How do our two hands develop independently of each other yet reach very similar size? How does a liver precisely regenerate its original mass when two-thirds of it is removed? The coordination of cell proliferation and cell death is essential for proper organ size during development and for maintaining tissue homeostasis throughout postnatal life
The recent discovery of a novel signaling network in Drosophila, known as the Hippo (Hpo) pathway, might provide an important entry point to these fascinating questions. The Hpo pathway consists of several negative growth regulators acting in a kinase cascade that ultimately phosphorylates and inactivates Yorkie (Yki), a transcriptional coactivator that positively regulates cell growth, survival, and proliferation. Components of the Hpo pathway are highly conserved throughout evolution, suggesting that this pathway may function as a global regulator of tissue homeostasis in all metazoan animals. (Pan D ( 2007) Genes Devel. Hippo signalling in organ size control. vol 21, : 886-97)
In Drosophila, cell proliferation and cell death are orchestrated by the Hippo kinase cascade, a growth-suppressive pathway that ultimately antagonizes the transcriptional coactivator Yorkie (Yki). A single phosphorylation site in Yki mediates the growth-suppressive output of the Hippo pathway. Hippo-mediated phosphoryiation inactivates Yki by excluding it from the nucleus, whereas loss of Hippo signaling leads to nuclear accumulation and therefore increased Yki activity. A mammalian Hippo signaling pathway also culminates in the phosphorylation of YAP, the mammalian homolog of Yki. The mammalian Hippo pathway is a potent regulator of organ size, and that its dysregulation leads to tumorigenesis. ( Dong J ( 2007,) Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell, 130, 1120-33 )

Which is part of the explanation for why a mouse and an elephant are somewhat different in size.
As an aside it is fascinating how such complex and far reaching are controlled by phosphorylation, acetylation and methylation.



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Effect of season on diet during pregnancy and infant outcome

The diet that the Mother eats during the pregnancy must be important for the baby
So an exciting and intriguing paper from New Zealand appears in the European Journal of Clinical Nutrition examining whether seasonal variation of nutrition in pregnancy effects infant measures and the health of the baby.
The authors PE Watson and BW McDonald looked at whether there was any seasonal effect on nutrient intake during pregnancy and birth measurements, secondly if there was any relationship between maternal nutrient intake and infant birth measure according to season and thirdly to test the hypothesis that seasonal change in nutrient intake might effect health in later life of some mothers offspring.
A great idea, though in our society the super market neutralises the effect of seasons by having similar foods available all the year round.
They studied 214 pregnancies in lower Northern New Zealand.
Significant seasonal variation was found for fat, carbohydrate ,electrolytes, vitamin and trace metal intake.
There was no effect on gestational weight and head circumference. with season. There were significant effects of birth measures and specific maternal nutrients at months 4 and 7 of pregnancy.
They conclude that seasonal nutrient variation may affect foetal development.
PE Watson and BW McDonald 2007, European Journal Clinical Nutrition, vol 61, 127-1280

History of Italian Food by John Dickie

Italy is such a mix of cultures from the North with the great City States to the South and Sicily extending into the Mediterranean absorbing the flow of cultures passing by through the centuries.
This great mix is reflected in the wonderful cuisine that Italy enjoys. Even the French cuisine owes something in part to an Italian Princess marrying into the French Royal family and bringing her own Italian Chefs and food delicacies.
Where ever Italians have migrated they have transformed the local diet with their food. To the extent that a well known English Model on returning home said that whilst she was abroad that she had longed for good English food like spaghetti.
John Dickie has written a fine history of Italian food which makes good reading.
The glory of nutrition is the translation of science into an agreeable meal. And the Italians have instinctively achieved this.
John Dickie The epic history of the Italians and their food Hodder and Stoughton

Obesity by country and especially Scotland

Scotland is the second-fattest nation in the developed world, with only the United States having higher obesity levels, a report revealed yesterday.
Figures show for the first time the full extent of the link between obesity and serious illness in Scotland, with obese people 18 per cent more likely to receive hospital treatment than those of normal weight
Women are particularly likely to develop serious health problems from being obese, according to the report by the Scottish Public Health Observatory, a collaboration of public health information bodies in Scotland.
Obese women are nearly 13 times more likely to develop type 2 diabetes than women of normal weight, more than four times as likely to suffer from high blood pressure, and about three times as likely to develop cancer of the colon. They are nearly 30 per cent more likely to suffer a stroke.
Obese men are more than five times as likely to develop type 2 diabetes than those of normal weight, 2.6 times as likely to suffer from high blood pressure and about twice as likely to develop osteoarthritis. Their chances of suffering a stroke are also 30 per cent higher.
Based on 2003, the most recent year for which figures are available, nearly 500,000 cases of high blood pressure, 36 per cent of the total, and more than 50,000 cases of coronary heart disease were a direct result of obesity, according to the report About 900 cases of cancer, mostly of the colon, were also attributed to obesity.
Under new rules for Schools in Scotland , at least two portions of fruit and vegetables will be served every lunchtime, oily fish will he served once every three weeks, while deep-fried food will be limited to three items a week. Sweets and fizzy drinks will be removed from schools and chips will be served only as part of a balanced meal.
Top of the table (per cent)
United States 32. 2
Scotland............................... .25.5
Mexico.................................. 242
UK (as a whole)................... 23
England................................ 22.5
Canada.................................. 22.4
Greece................................... 219
Australia........................ _...... 217
New Zealand....................... 20.9
Hungary............................... 18.8
Czech Republic
And at the bottom
Germany............................... 12.9
France........................ ~......... 9.5
Italy........................................ -9
Norway.................................. 8.3

Times Sept 26th 2007 p 11

Maternal Mortality Rates in India.

No one could dispute the central place that a mother has in the upbringing of young children particularly in unsophisticated societies.
In Victorian times a pregnant woman would in addition to preparing clothes for the baby prepare her shroud for the strong possibility that she would die during the delivery or shortly after.
In India the Maternal Mortality Rate has fallen over the last 10 years from 407 per 100,000 live births to 301 per 100,000 life births.
Some 77,000 women die a year from causes related to pregnancy. Many could be prevented.
The more remote and less structure the society the higher the death rate. An exception is Kerala which has a high literacy rate and Maternal Mortality Rae of 100 deaths per 100,000 live births.
Critical to the care of these women is awareness of the danger and transport to medical care. Anaemia is widespread
In Aberdeeen in the early 20th century there were many women with a haemoglobin of under 5 g/100ml. Simple iron therapy restored their blood concentrations
Chattergee P,(2007) India addresses maternal deaths in rural areas Lancet vol 370, 1023-4

Mortality among under 5 year olds world wide

The annual number of deaths of children aged under 5 years has dropped to less than 10 million last. Still a terrible figure.
www.unicef.org
Of these half were in sub Saharan Africa. ( 4.8 million ( due to HIV and AIDS) and 3.1 million rom south Asia.
The figure for West and Central Africa is 186 deaths per 1000 children under 5 years compared with 6 per 1000 in Western industrial countries
China and India has made great advances in caring for the young
Achieved by simple procedures such as
Immunisation against measles
Exclusive breast feeding
Vitamin A supplements
Use of bed nets treated with insecticide against insect carrying malaria.
Treatment of malaria, pneumonia, diarrhoeal diseases and severe malnutrition , HIV and Aids.
Murray CJL et al 2007 Can we achieve Millenium Development Goal 4? New analysis of country trends and forecasts of under-5 mortality to 2015. Lancet, vol 370, 1040-54

Mortality among under 5 year olds world wide

The annual number of deaths of children aged under 5 years has dropped to less than 10 million last. Still a terrible figure.
http://www.unicef.org/
Of these half were in sub Saharan Africa. ( 4.8 million ( due to HIV and AIDS) and 3.1 million from south Asia.
The figure for West and Central Africa is 186 deaths per 1000 children under 5 years compared with 6 per 1000 in Western industrial countries
China and India has made great advances in caring for the young
Achieved by simple procedures such as
Immunisation against measles
Exclusive breast feeding
Vitamin A supplements
Use of bed nets treated with insecticide against insect carrying malaria.
Treatment of malaria, pneumonia, diarrhoeal diseases and severe malnutrition , HIV and Aids.
Murray CJL et al 2007 Can we achieve Millenium Development Goal 4? New analysis of country trends and forecasts of under-5 mortality to 2015. Lancet, vol 370, 1040-54