Alcohol metabolism

Alcohol dehydrogenase (ADH) and mitochondria! aldehyde dehydrogenase (ALDH2) are responsible for metabolizing the bulk of consumed ethanol . These enzymes also affect the rate of ethanol elimination from the blood. They are expressed at highest levels in liver, but at lower levels in many tissues. This pathway probably evolved as a detoxification mechanism for environmental alcohols.
However, with the consumption of large amounts of ethanol. the oxidation of ethanol can become a major energy source and. particularly in the liver, interferes with the metabolism of other nutrients. Polymorphic variants of the genes for these enzymes encode enzymes with altered kinetic properties.
The patho-physiological effects of these variants may be mediated by accumulation of acetaldehyde: High-activity ADH variants are predicted to increase the rate of acetaldehyde generation, while the low-activity ALDH2 variant is associated with an inability to metabolize this compound. The effects of acetaldehyde may be both in the cells, or by the acetaldehyde passing to various tissues by the bloodstream or even saliva.
Inheritance of the high-activity ADH β2. encoded by the ADH2*2 gene, and the inactive ALDH2*2 gene product have been conclusively associated with reduced risk of alcoholism. This association is influenced by gene-environment interactions, such as religion and national origin.
The variants have also been studied for association with alcoholic liver disease, cancer, foetal alcohol syndrome. CVD, gout, asthma and clearance of xenobiotics. The strongest correlations found to date have been those between the ALDH2*2 allele and cancers of the oro-pharynx and oesophagus.
Crabb et al 2004, Proceedings of the Nutrition Society (2004) vol 63, 49-63

Ageing and metabolic controls

Ageing is of interest to everyone, except the young who welcome growing older and those who don’t make old age.
Many ageing related genes which alter longevity for good or bad have been identified. A gene that influences ageing is the daf-16 gene which is called a gerontogene.
The protein encoded by daf-16 is a transcription factor which modifies the activity of other genes. This gene in the C.elegans worm and mice is a powerful influence on life span.
Daf-16 is turned off by hormonal signalling pathways similar to insulin and insulin growth factor.
There are two classes of genes affected by Daf-16
Class -1 genes ( there are 189 of these) are switched on and are associated with increased life span
Class -2genes ( there are 122 of these) are repressed and are associated with reduced life span
The effect of Daf-16 is additive and requires the combined activity of many of these genes.
So what is a ageing. Is it the accumulation of metabolic rubbish? ( It feels like this ) or some other process ? Or some as yet unthought of process.
It is interesting that a recent blog that I wrote confidently proposed that ageing was accumulated DNA damage,
Of interest to all of us.
Gems and McElwee Nature 2003, vol 424, 259-261
Murphy et al Nature 2003, vol 424, 277-283

Brain thoughts

As vertebrate embryo grows, the development of its brain and spinal cord is controlled by complex and precisely regulated patterns of gene activity. Writing in Nature Lacalli ( Nature 2003, vol 424 , pp263-4) reviews a paper discussing the genes responsible for patterning the body along its antero-posterior axis (that is, from front to back), notably Hox genes and the like. These genes are highly conserved in evolution, with similar expression patterns in animals and such anatomically different creatures as insects and vertebrates. Insects and vertebrates are advanced members, respectively, of the two major divisions of animals, protostomes and deuteros tomes
These genes are expressed in the vertebrate brain and spinal cord and appear on the surface nerve net of a closely related group of invertebrates.
Understanding of the brain is fundamental to nutrition but is so complex as to be daunting If the brain has a common evolutionary basis with worms where in all of this comes the characteristics of the human brain. Intelligence, thought, creativity , emotions, wanting, perception of self, language, understanding free will , communication to name but a few.
Baum in his book “What is thought” published by Bradford Books 2004 , MIT Press Cambridge Massachusetts proposes a computational explanation of thought. That life must be explainable at a fundamental level by physics and chemistry, Baum argues that the complexity of mind is the outcome of evolution, which has built thought processes that act unlike the standard algorithms of computer science, and that to understand the mind we need to understand these thought processes and the evolutionary process that produced them in computational terms.
Baum proposes that underlying mind is a complex but compact program that corresponds to the underlying structure of the world. He argues further that the mind is essentially programmed by DNA. We learn more rapidly than computer scientists have so far been able to explain because the DNA code has programmed the mind to deal only with meaningful possibilities. Thus the mind understands by exploiting semantics, or meaning, for the purposes of computation; constraints are built in so that although there are myriad possibilities, only a few make sense. Evolution discovered corresponding subroutines or shortcuts to speed up its processes and to construct creatures whose survival depends on making the right choice quickly. Baum argues that the structure and nature of thought, meaning, sensation, and consciousness therefore arise naturally from the evolution of programs that exploit the compact structure of the world.
He draws heavily on that basic principle oft disregarded in Nutrition namely Occam’s razor, the dictum of the 14th Century philosopher, “Entities should not be multiplied unnecessarily”, and he is looking for straight forward simple laws to govern this complexity. His other basic rule is Bayesian statistics which is a rational way of calculating and revising probabilities and beliefs during change .The concept of meaningful possibilities which he relates to the flexibility of change during evolution. It makes sense that brain structure is modelled on a template of DNA. The complex inter connections by which the brain functions are a different matter. Theories based on systems that we have created e.g. the computer are forms of anthropomorphism. Heady or even brainy stuff
It does not help us however with .
Where does consciousness start?.
What is thought or creativity?
Why do some have convergent and others divergent minds?
If we ensure that the developing mind receives a sufficiency of long chain fatty acids and other nutrients what element of intelligence do we improve or is it an overall improvement. Is creativity or memory changed? Does the spectrum of long chain fatty acids matter.? .

Public Health Statistical Indicators

Nutritionists and other Professionals use statistics to help decide what is best for the general public. This is a very important paper in Lancet setting out the principles that are necessary for good practice. (Murray Lancet 2007, vol 369, 862-73)

Towards good practice for health statistics: lessons from the Millennium Development Goal health indicators
Health statistics are at the centre of many global health controversies. Several factors are influencing the supply and demand for high quality health information. The health-related Millennium Development Goals give a good example.
Thousands of indicators are recommended but of them are well measured. The international health community needs to focus its efforts on improving measurement of a small set of priority areas. Priority indicators should be selected on the basis of public-health significance and measurability.
Health statistics can be divided into three types: crude, corrected, and predicted.
Health statistics are prerequisites for planning and strategic decision making, programme implementation, monitoring progress towards targets, and assessment of what works and what does not.
Crude statistics that are biased have no role in any of these steps; corrected statistics are preferred. For strategic decision making, when corrected statistics are unavailable, predicted statistics can play an important part.
To monitor progress towards agreed targets and assessment of what works and what does not, however, predicted statistics should not be used.
The most effective method to reduce the controversies over health statistics and to encourage better primary data collection and the development of better analytical methods is a strong commitment to provide an explicit data audit trail.
This initiative would make available the primary data, all post-data collection adjustments, models including covariates used for farcasting and forecasting, and necessary documentation to the public.

Definitions of technical terms
Indicator
A variable measured to monitor progress or assess what works and what does not.
Validity
Validity refers to the extent to which a measurement is capturing what it is intended to measure. There are different types of validity such as face validity, content validity, criterion validity (denoting predictive validity and concurrent validity), and construct validity (denoting convergent and discriminant validity).
Reliability
Reliability refers to the repeatability or consistency of a set of measurements or measuring instrument, for example, test-retest reliability where a test and a retest are compared.
Comparability
Measurements arc comparable if the same value means the same thing in the settings being compared. Two thermometers, one in Farenheit and one in Celsius, can both be valid and reliable but they do not give comparable results.
Out-of-sample
Prediction about ranges of values that are not in the investigator's sample (ie, that the investigator's data set does not cover).
Out-of-time
Prediction about individuals, populations, etc, in time outside
the time range of the investigator's sample.
Forecasting
Forecasting is the process of estimation in unknown situations. Predicting is a moie general term and connotes estimating for any time series, cross-sectional, or longitudinal data Forecasting is commonly used when discussing time series data.
Farcasting
Farcasting is trying to predict the value of a variable in a place that may be far away but is not a future value.
Prior
The prior is a reflection of some information the investigator has before the observations in the data set (the investigator should state explicitly how the information on the prior was obtained). The prior is the sum of what is known about the relationship under study.


Murray Lancet 2007, vol 369, 862-73

Hot drinks and sweetness

Temperature has a strong influence on how we taste. The sweetness of diluted sugar solutions increases strongly with temperature. Merely cooling or heating the tongue is sufficient to cause sensations of taste in approximately 50% of subjects.
Several members of the TRP super family function as thermosensors and this has been studied by Talavera et al Nature 2007, vol 438, 1022- 1025 to attempt explain what is happening in the tongue. The TRP super family are Transient Receptor Potential channels .
TRPM5, is an intra-cellular calcium -activated, voltage-dependent channel of the TRP superfamily, and is highly expressed in taste buds of the tongue, where it has a key role in the perception of sweetness , umami and bitter tastes. Activation of TRPM5 occurs downstream of the activation of G-protein-coupled taste receptors and generates a depolarizing potential in the taste receptor cells:. Factors that influence TRPM5 activity are therefore expected to influence taste.
Talavera et al have shown that TRPM5 is a highly temperature-sensitive, heat-activated channel. Inward TRPM5 currents increase steeply at temperatures between 15 and 35 degrees centigrade
Increasing temperature between 13 and 35 degrees centigrade markedly enhances the gustatory nerve response to sweet compounds in mice. The strong temperature sensitivity of TRPM5 may underlie known effects of temperature on perceived taste in humans, including enhanced sweetness perception at high temperatures and ‘thermal taste’, the phenomenon whereby heating or cooling of the tongue evoke sensations of taste without any taste being involved.
Which is why a hot sweet cup of tea can taste so deliciously in certain circumstances. It’s the TRPM5 at work.

Functional foods

Functional foods

Functional foods are modified foods that claim to improve health quality of life or well being.
To many these are a cause for concern.
The producers of these products seize on some half fact, utilise this to sell a well priced product to a gullible public. My wife and I have raised cholesterol concentrations and for 6 months religiously took a stanol containing yoghurt with no change in our cholesterol concentrations .
There are more than 200 different functional foods which claim all manner of health wonderments.
They include
Enrichment with phytosterol-stanols to affect low density lipoprotein cholesterol
Bioactive peptides blood pressure
Enrichment with melantonin sleep inducemen
Omega 3 fatty acids depression, triglycerides, joints
Beta glucan blood sugar and low density lipoprotein cholesterol
Prebiotics bowel function
Probiotics diarrhoea
Calcium and vitamin D bones
Protein or bioactive peptides obesity, appetite

The EU is now starting to look at this hotch potch of claims and conducting evaluations of the products. A new drug has to be tested in a series of very demanding tests. A new food just turns up on the shelves.
The European Food Safety Authority is now establishing serious requirements for nutritional claims.
About time.
De Jonge et al BMJ 2007, vol 334, 1037-1039

Ageing

There are many theories of why we age, Curious we accept the ageing of a car or some tool more than ourselves. We accept growth but decline and its anticipation of death is less attractive. More personal perhaps.
Theories of ageing include the accumulation of toxins produced by gut bacteria (curable by eating yoghurt) and reduced secretions from the testicles (curable by transplants of testicular tissue from monkeys. ).
Jan Vijg has written a book Aging of the Genome: the dual role of DNA in life and death published by Oxford University Press Reviewed by Linda Partridge Nature 2007, vol 447, pp 262-3
The current accepted theory is that ageing is caused by the accumulation of random alterations to DNA in somatic tissues (all tissues other than the reproductive germline cells). What is not known is the damage responsible for functional impairment and death, and the processes that generate this damage and protect against it. Though the usual culprits ,( smoking reduces life expectation by 11 years, excess alcohol, weight , blood pressure and poor diet) must get a look in .
DNA is being constantly bombarded with chemical and physical challenges that induce random alterations, including structural damage and changes in nucleotide sequence and organization. But unlike proteins and lipids, the damaged DNA cannot be simply broken down completely and remade, because it holds unique information. Instead, cellular pathways detect alterations and dependent on the type of cell and the nature of the changes, this variously leads to DNA repair, arrest of the cell cycle (preventing cell division), cellular senescence or death, or toleration of the change. In some cell types, some forms of DNA alterations accumulate with age, with evidence for genomic hotspots and considerable variation between individuals. Cancer is a clear case where DNA alterations can give rise to age-related pathology; their role in other aspects of functional decline is less clear, with the exception of mutations in DNA within mitochondria, the organelles that power cells.
Vijg : Aging of the Genome: the dual role of DNA in life and death published by Oxford University Press Reviewed by Linda Partridge Nature 2007, vol 447, pp 262-3

whippets, speed and MSTN mutation

Whippet are very fast runners, can reach 60 km an hour and have traditionally been used for racing. A rather unfortunate complication has arisen in that some whippets are experiencing doubling muscling, a cramp in the shoulders and thighs.
This is due to a mutation on the MSTN gene which encodes myostatin, a protein important in muscle composition. This mutation involves the deletion of only two DNA bases.
If the dog has mutations in both copies of the MSTN gene then they have the double muscling problem. The parents will have only one mutation.
There is a relationship between speed, muscle mass and a single mutation of the MSTN.
Selective breeding of whippets but not other heavy muscled dog breeds leads to this double muscle condition.
Reported by Shadam in Nature 2007, vol 447, p 274

Genetics,nutrition, environment and health

Genetics,nutrition, environment and health
Can a well established known environmental or dietary threat or precipitant of ill health affect a person who does not have the innate genetic predisposition?

heart disease risk and SNPs

In Science there are two recent reports of single-nucleotide polymorphism ( SNP) which give an enhanced risk of heart disease in white populations. These are found in the same tight area in chromosome 9 , in a non coding region close to two tumour suppressing genes. ( Science doi:10.1126/science 1142447 and doi : science 10.1142843 (2007).
Those individuals who carry one of these high risk clusters have a 30-40% increase in having heart disease and possessing both increases the risk to 64%.
Which is very interesting but does not say what happens if one ignores the usual prudent advise of not smoking, weight control, diet and exercise.
In the great Novel, “The confessions of a justified sinner” James Hogg , describes how a man belonging to a fundamental Christian Faith was told by his Minister that he was saved. So the hero went out and lived a raucous life as he was confident that he was eventually going to Heaven.
Does having a clean sheet in terms of predisposing genetic SNPs in ones DNA remove the need to be prudent?
Not worth the risk. The important pointers are surely there for us all.

whole body protein turnover methods

Protein turnover is the continual synthesis and breakdown of protein in the body. This is a core process in biology and many talents have attempted to measure this in the whole body .
The use of radio labelled amino acids requires a model system to enable calculations.
Q = I + B + N = S + M + C
Q is the flux of the amino acid, I the dietary intake, plus the input from protein breakdown B and N is the input from de novo synthesis. The flux is equal to the incorporation of the amino acid into body protein S, oxidation and other forms of metabolism M. There is small additional loss from the gastrointestinal tract as faeces
( 1 g N / day ) , skin ( 20 mg N / kg body weight ) and non measurable urinary uric acid ( 3 % of urinary nitrogen). Q can be calculated with the flux based on NH3 ( Q A ) or on urea (Q u ).
In human studies stable isotopes are used eg 13 C and 15 N. The amino acid chosen is usually leucine as this has one catabolic pathway and is predominantly metabolised in muscle. The amino acid can be given orally or more usually intravenously for 2 hours to achieve a plateau enrichment of the plasma . If leucine is used, its muscle metabolic product a-keto isocaproic acid (KIC) is used for measurement, being a better indicator of intracellular leucine enrichment. Such methodology requires
1. that a steady state plasma concentration of tracer is achieved
2. the dose of tracer has no consequences for the metabolism of the tracer.
3. the labelled and unlabelled amino acids are metabolised identically
4. no significant recyling of the isotope occurs
5. the enrichment in plasma is representative of that at the site of protein synthesis.

In a review Duggleby and Waterlow ( British Journal of Nutrition 2005, vol 94, pp 141-153 ) have analysed an cheap alternative , the end product approach using labelled glycine. This method has merit for population results.
This method relies on a two-pool model , and that the two products of the same precursor have the same labelled activity. The other assumption is that the activity of the end product reflects the amino acid-N mixture taken up into protein. The end products of ammonia or urea may not give the same result.
In the complex of all the proteins in the body and their varied rate of turnover this is a basic assumption, and is reflected in the range of inexplicable results.
If nitrogen flux is measured in the same subject over a period of time using a range of amino acid precursors then the measure of protein synthesis ( mg protein /kg per hour) ranges from 70 to 1038 ) and between oral and intravenous. However closer results are obtained from the individual amino acids. Few studies have been made on the same subject using different labelled amino acids at the same time.
In many respects this is an unresolved and demanding area.
Review Duggleby and Waterlow (British Journal of Nutrition 2005, vol 94, pp 141-153)

human genetic variaiton mapping

The large studies of human genetic variation have concentrated on understanding the pattern and nature of single- nucleotide differences within the human genome. There are larger polymorphisms for example insertions, deletions and inversions, Which leaves much to be studied .in human structural genetic variation. The National Human Genome Research Institute (NHGRI propose to sequence large-insert clones from many individuals, from all racially diverse groups systematically discovering and resolving the complex variants at the DNA sequence level.
The sequencing of the human genome has revolutionised human biology and genetic medicine. However it is anticipated that the sequencing of individual human genomes is necessary for a comprehensive genetic understanding of disease. The cost of such efforts is prohibitive.
The discovery of functionally important genetic variation lies at the core of these endeavours, and there has been considerable progress in understanding the common patterns of single-nucleotide polymorphism (SNP) in humans. Of the estimated 10-15 million common human SNPs, a significant fraction have now been identified and genotyped among population samples (Hap.Map release 21).
Understanding the structural variation in the human genome is less advanced .Structural variation can be defined as all genomic changes that are not single base-pair substitutions i.e. insertions, deletions, inversions, duplications and translocations of DNA sequences, and copy-number differences (also known as copy-number variants, CNVs. .Thee are large-scale (>100 kb), intermediate-scale (500 bp-100 kb) and fine-scale (1-500 bp) structural variations in the human genome. Structural changes are common, and frequently involve the rearrangement of genes. It is important to establish a baseline of normal structural variation to allow the discovery and characterization of disease-causing mutations in patients.
There are considerable variation between normal human genomes, with more than 1,447 copy-number variant regions spanning 12% of the reference DNA sequence. It still remains important to identify which specific DNA sequences have been altered, and the molecular events that have given rise to these structural genomic variants.
Previous methodology has been unable to show structural variation events that have arisen as a result of balanced chromosomal rearrangements (such as inversions or reciprocal translocations of chromosomal segments). The frequency of such balanced events is unknown, a guess is 1-20% of all structural variation may in fact be balanced and does not involve copy-number changes.
Such human genetic traits as such as colour blindness, rhesus blood group sensitivity, classical haemophilia and forms of beta- and alpha- thalassaemia result from complex structural alterations in genes and gene families Other traits involve large, structural rearrangements of chromosomes for example, Prader-Willi syndrome. Structural genetic variation can confer phenotypes through several mechanisms, gene dosage (copy-number variation); gene disruption; gene fusions at the junction; position effects in which the rearrangement alters the regulation of a nearby gene; and unmasking of recessive mutations or functional SNPs on the remaining allele. Another possible mechanism could occur through perturbations of gene expression that normally result from the pairing of homologous allele. .
Several common structural genetic variants (>1% minor allele frequency) have been shown to be important in both normal phenotypic variability and disease susceptibility.
These examples highlight the importance of structural variation to disease and disease susceptibility, and suggest several concepts of potentially broad relevance.
1., the number of copies of a given gene or family of genes can be a direct risk factor for specific diseases.
2. Copy number alone may not explain phenotypic differences caused by structural genetic variation. In rhesus blood group sensitivity, colour blindness and the alpha- and beta-thalassaemias, the precise DNA sequence structure (that is, the formation of fusion genes or the position of a gene with respect to functional promoters) provides the most meaningful associations between genotype and disease
3. Normal structural genetic variation can increase the risk of secondary, pathogenic rearrangement.
The Human Genome Structural Variation Working Group ( Eichler et al ) Nature 2007, vol 447, 99161-165

Stamina food for 10 year old footballers

Stamina and Juvenile football teams

I have a grandson who plays in an under 10 year old football team. The boys include several who are included in a Scottish Premier Division Football Academy.
They play with all the commitment and activity of little boys b they always flagged in the second 25 minute half. This left them vulnerable to loosing goals. The team includes several boys from underprivileged homes and whose nutrition is far from good. These boys are often given money to buy a bag of chips as their evening meal. These boys are resistant to any offer of food acceptable to a nutritionist.
So what does one give them to enhance stamina?
One Scottish Premier Division Club gives the players wine gums before the game, presumably as slow release sugar
We gave our young boys a small Mars bar before the game and a similar one at half time and afterwards
The change in stamina was striking in the most demanding game of the season. Hopefully we can persuade them to eat pasta the night before.

Methylation and acetylation in genetic control processes

Nutrition has had to come to terms with the domination of science by molecular biology. Can Nutrition find a place in the science of the post translational events by providing substrates for the modulation of these genetic metabolic programme?.
Hints are given by studies describing small molecular transfer reactions.
Acetylation as a regulatory post translational modifier. The general transcription factor TFIIB which is prerequisite for the initiation of polymerase II activity is acetylated. Acetyl CoA is involved in this reaction ( Choi et al Nature 2003, vol 424, pp 965-9 )
Methylation is involved in cancer linked epigenetic alteration , either through hypomethylation or hypermethylation . The breast cancer drug tamoxifen is a drug with distinct genomic activity and gene transcriptional regulation. ( Wu et al Nature 2005, vol 438, , pp 981- 987
Nicotinamide riboside increases the concentrations of nicotinamide adenine dinucleotide which activates the age related protein Sir2, well anyhow in yeast. Nature 2007, vol 447, p 118
Folic acid is a determinant of DNA methylation which is important in DNA activity. Ageing is associated with DNA hypomethylation. ( Choi et al 2005, British Journal of Nutrition vol 93,pp31-35)
The inhibition of histone deacetylases can improve memory capabilities in a genetically engineered mouse model of neurodegenera-tion in the central nervous system . Histone deacetylases remove acetyl groups from lysine amino acids in proteins, including the cell nucleus histones. Histones interact with DNA to form chromatin which control the accessibility of DNA for gene transcription. Acetylated histones form active chromatin complexes with DNA, which makes the DNA accessible to RNA polymerases, thereby regulating gene transcription
Inhibitors of Histone deacetylases block the ability of these enzymes to deacetylate histones, promoting histone acetylation in the nucleus and thus altering gene expression. Because altered transcription is known to be necessary for the formation of long-term memories, Histone deacetylases inhibitors have the potential to boost memory formation. This has been demonstrated in normal rats and mice
Sweatt Nature 2007, vol 447, pp151-152
Fischer et al Nature 2007, vol 447 pp 178-182.
There is much potential here for exciting studies.

Under 5 year old mortality in Thailand

Mortality in children under 5years is a sensitive index of the well being of a society.
In Thailand there is a National project to reduce mortality in under 5 year old.
In the 1950s and 60s the under 5 year old mortality was 160 per 1000 and this had been reduced to under 40 by 1990. Since then there has been a further 24% reduction
Clearly this is a top Government priority.
There has also been a marked reduction in inequality between the riches and the poorest in society.
A major improvement in household economic status is a major component. In Thailand a measure of poverty is the proportion of the population living on less than 1 US $ a day.
The practice of culling baby girls ( female feticide ) has to be abolished but exists even in civilised Eastern countries. Tolerance of religious and ethnic minorities is important.
A range of free health improvement schemes for the poor is also important, especially for the poor rural populations. This includes community hospitals and vaccination and anti polio programmes. Dedicated Medical teams have proved to be important.
It is also important to identify pockets of poverty and at risk groups.
Vapattanawong et al Lance2007, vol 369, 850-855
Bhutta Lancet 2007, vol 369, 804-806

A survey of adults taking dietary supplements.

Dietary supplement survey. Harrison et al Brit Journal Nutrition 2007, 91, 617-23.

The authors of this paper surveyed 21923 adults asking them of their usage of dietary supplements along with a self assessment of health and twelve item general health questionnaire in the Bolton and Wigan area of Lancashire. They were also asked about exercise, smoking and fruit, vegetable and fish oil intake Their ethnic and social and economic status was also asked for.
A mammoth and important study.
Over 95% of replies were from white adults.
Over one third ( 35.4 %) took supplement. This group tended to be older, female, homeowners, , none smokers, physically active and white. The use of vitamin supplements was often in association with five pieces of fruit and vegetable a day. Taking fish oil supplements was in addition to one oil rich fish a week.
Those who took these supplements were physically fitter. There was increased
usage of fish oils in individuals troubled with musculoskeletal problems.
Individuals with cardio vascular diseases tended not to take any supplements.
The official view amongst Dietetic experts is that most people eat a diet which makes supplementation unnecessary. Ignoring the wish to do something natural, prudent , sustaining and cosseting to be healthy.
This is a practice generated by Nutrition literature and acted upon by the thinking public. Even if their logic is not totally correct. .It would be very interesting to know how the individuals decided to take a supplement. Gossip over tea or Bridge, daughters fussing over their Mums or reading magazines . Or none of the above.

Obituary of Schmidt-Nielson; Animal Physiologists

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, cool 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

autophagy and starvation

Autophagy
Autophagy occurs when cells need to degrade their constituents. This occurs in most normal cells to prevent the accumulation of protein aggregates and defective cellular substructures. During starvation, high temperature, low oxygen, hormonal stimulation or intracellular stress (damaged organelles, accumulation of mutant proteins, microbial invasion) there is activation of signalling pathways that increase autophagy.
The enzyme TOR kinase is a sensor of nutrient status and a major regulator of cell growth; negatively regulating autophagy acting through autophagy-execution proteins. Various signalling pathways, such as those involved in the control of cell growth, DNA-damage repair, programmed cell death (apoptosis) and immunity also induce autophagy. .
After the cell receives the appropriate signal, the autophagy-execution proteins trigger a cascade of reactions leading to membrane rearrangements forming a double-membrane-bound vesicle called an autophagosome. An isolation membrane forms, which surrounds the cytoplasmic contents to be degraded, creating a sac the autophagosome. This vesicle then fuses with a lysosome (or a vacuole in yeast), with the release of lysosomal digestive enzymes into the lumen of the resulting autolysosome. The sequestered cytoplasmic contents are degraded inside the autolysosome into free nucleotides, amino acids and fatty acids, which are reused by the cell to maintain macro-molecular synthesis and to fuel energy production. The nutrient recycling and housekeeping functions of autophagy allows cell survival, although in certain circumstances autophagy may promote cell death
Autophagy may also stop routine protein synthesis to allow the synthesis of essential proteins when external nutrients are limited. During starvation, autophagy comes into play to ensure that the cell has sufficient amino acids to synthesize the proteins that are essential for its survival . However the synthesis of specific stress-response proteins, including autophagy-execution proteins are turned on. A coordinated strategy. and autophagy is activated.
The autophagy-specific genes are encode proteins that are components of kinase complexes, which regulate the activity of proteins and lipids through the addition of a phosphate group. Alternatively, they encode components of protein-conjugation systems, which attach to each other or to membrane lipids to form the membrane of the autophagosome.
Autophagy and apoptosis are usually been classified as different forms of programmed cell death. Whereas apoptosis invariably leads to cell death, autophagy (despite its frequent occurrence in dying cells) commonly contributes to cell survival. There is a complex, and not fully understood, relationship between autophagy and apoptosis that may vary depending on the biological context. The two pathways are regulated by common factors; they share common components; they can exert overlapping functions; and one pathway may regulate and modify the activity of the other.
Autophagy and apoptosis may occur in the same cell, both when autophagy is trying to keep cells alive and when it contributes to cell death. In some circumstances, e.g. starvation and treatment with certain DNA-damaging agents, autophagy delays the onset of apoptosis.
Review in Nature Levine Nature 2007, vol 446, 745-7

Protein modification and function

Polypeptides after synthesis on the cell’s protein-assembly apparatus require further elaboration for use. Both the peptide backbone and its side chains may need to be altered by post-translational modifications , the covalent attachment of chemical groups that change the properties, and hence the function, of newly generated proteins. Post-translational modifications also control the degradation of aberrant proteins and proteins at the end of their lifespan. Such modifications dramatically expand the compositional and functional complexity of these molecules.
Proteins may exist as a mixture of forms, each incorporating different post-translational modifications.
One intricate form of post-translational modifications is the attachment of carbohydrates, glycans, either to nitrogen atoms (N-linked) in the side chains of asparagine amino acids, or to oxygen atoms (O-linked) on the side chains of serine or threonine. In living cells, glycosidase and glycosyl transferase enzymes first trim N-linked glycans, then extend them with sugars that can branch in several directions, generating numerous variations on a theme. Glycosyl transferases also act on O-linked glycans, imposing similar extensions and modifications. To add to the complexity, each sugar can bear different chemical groups, and the linkages between sugars have specific orientations. Many biological processes, such as cellular differentiation and development, cell adhesion, immune surveillance and inflammation, rely to varying degrees on the correct decoration of proteins with such glycans.
Grotenbreg and Ploegh Nature 2007, vol 446, pp 993-995.

Iron, plankton and place in carbon dioxide usage.

The Southern Ocean plays a major role in the climate system, and is recognized as the ocean most sensitive to climate change . The control of biological productivity e.g. the phytoplankton community by iron in the Southern Ocean has been shown by iron adding experiments.
The availability of iron limits biological productivity and the associated uptake of carbon over large areas of the ocean. Iron plays an important role in the carbon cycle, and changes in iron supply to the ocean surface may have had a significant effect on atmospheric carbon dioxide concentrations.
Blain and his colleagues in Nature 2007, 26th April , vol 446, pp 1070-74, have shown that a large phytoplankton bloom over the Kerguelen plateau in the Southern Ocean is maintained by the supply of iron and major nutrients to surface waters from iron-rich deep water below. The efficiency of fertiliz­ation, defined as the ratio of the carbon export to the amount of iron supplied, was at least ten times higher than previous estimates from short-term blooms induced by iron-addition experiments’. This result sheds new light on the effect of long-term fertilization by iron and macronutrients on carbon sequestration, suggesting that changes in iron supply from below may have a more significant effect on atmospheric carbon dioxide concentrations.
However another major factor is the availability of carbon to convert into organic materials. ( Boyd Nature 2007, vol 446, pp 989-90.
Blain and his colleagues in Nature 2007, 26th April , vol 446, pp 1070-74

The chicken as food, a book

I was brought up in Farming. When I was a teenager the poultry trade was free range hens or at the most confining wire surrounded runs for the hens. The lucky poultry roamed the fields. Then came deep litter and then the intensive farming of poultry. If you go to a super market the ready made meals are primarily chicken in any food style you like. Indicating the size of the industry. The birds are bred and reared to mature at a remarkable rate.
Any one who has seen or looked in the sheds where there is intensive farming of hens or who has seen the chicken processing factories might feel less keen on these delicacies.
A book devoted to this topic is
Planet Chickens; The shameful story of the bird on your plate. By Hattie Ellis published by Sceptre Publications

The Banana

The banana is the most popular fruit eaten in the UK, 95% of families buy bananas each week.
Whilst there are more than 300 varieties of bananas, the majority of bananas grown have been of one type, Gros Michel or Big Mike. A variety which has a universally acceptable taste, acceptable size, colour and sweetness. The modern popularity of bananas came as a result of the activities of the United Fruit Company in the USA which had plantations in the southern American states and Islands. The company developed the sale of these all over the world using a fleet of 100 refrigerated ships.
Hot and damp conditions are ideal for growing the banana. The mass production of the banana plants has lead to problems. The plants are readily infected by a variety of pathogens as the banana plant is a clone, inbred and has inherent vulnerability and susceptibility to a wide range of pathogens. The plants are grown from cuttings and the seeds are quite fragile. The climate must facilitate the activity of pathogens, warm and wet.
The variety of banana now used is the Cavendish and even this is dying.
The transport of bananas to the shops is a masterly exercise in transport. The time from cutting the bananas from the tree on the plantation to the distant shop must be within 12 to 13 days before rotting begins.
The banana plant requires intensive pesticide and fungicide application to keep the plants alive. Hence bananas are amongst the most chemically treated of any food we eat.
This description of the bananas way of life and the politics of the company ( United Fruit ) who developed its widespread usage is to be found in the Financial Times Magazine May 5/6 2007, pp 24-27; written by Peter Chapman
He has also written a book “Jungle Capitalists, a story of Globalisation Greed and Revolution published by Canongate. Press

Validation and reproducibility of Food Frequency Questionnaire

Villegas et al (2007) Validity and reproducibility of the Food Frequency Questionnaire used in the Shanghai men’s health study. British Journal Nutrition, 97, 993-1000
The accurate estimates of food intake over long periods is a real necessity and poses a methodology problem for diet-disease research. .One method is the Food Frequency Questionnaire. Short-term recalls and diet records are expensive and not very accurate. Especially in taking diet histories from the past. Food Frequency Questionnaires have been the primary method of dietary assessment for most epidemiological studies. Food Frequency Questionnaire are easy and cheap to use They are however very sensitive to the cultural and dietary practices of populations. .The food list which the questionnaire is based is very important. The list shown to the population being studied must contain the foods eaten by that population,
The validity and reliability of an FFQ needs to be evaluated for the specific population being studied. of concern. In many epidemiological studies, however, the main concern is to classify individuals into different groups according to exposure levels rather than to assess their absolute intake. Thus, comparisons of percentage agreement in quartile distributions are also often used in the evaluation of the validity and reliability of a Food Frequency Questionnaire.
The validity and reproducibility of Food Frequency Questionnaires in multiethnic populations has been investigated before. For absolute nutrient intakes, the correlations were greatest for whites, somewhat lower for Japanese-Americans and Latinos, and lowest for African-Americans . A complication is food choice. In Shanghai, women are mainly responsible for purchasing and preparing foods for the family and. thus, are more likely to estimate their dietary intake accurately than men.
Villegas and his colleagues believe that the dietary recall information obtained from this study is a fairly accurate measurement of the true usual intake for this study population over a 1-year period. Multiple dietary recalls may sensitise study participants regarding their dietary intake, and thus participants may answer the Food Frequency Questionnaire more accurately, resulting in an overestimation of intake. On the other hand, changes in dietary intake during the year must also be identified.
Food Frequency Questionnaires overestimate soy. fruit and vegetable intake, and slightly underestimated poultry, red meat, fish and egg intake. Some of the measurement error may reflect a bias of study participants seeking social approval.
Villegas and colleagues concluded that Food Frequency Questionnaires appropriate for the population under study can reasonably categorise usual intake of major nutrients and food groups. Food Frequency Questionnaires. may under- or overestimate the absolute amount of intake of some nutrients or foods.

Undernutrition in in early life and influence on adolescent body composition

Undernutrition in early life and body composition on reaching adolescence in males.
Gigante et al, British Journal of Nutrition 2007, 97, 949-954
In middle- and high-income countries there is an epidemic of excess weight and obesity. This has attracted a number of studies to determine the early determinants of adult size. One possibility is that individuals who have suffered under nutrition in early life, followed by Western-type diets might be at risk of overweight and chronic disease.
The association between stunting and overweight in children has been shown in a cross-sectional study in four countries in nutritional transition (Russia. Brazil. South Africa and China). The risk of being overweight for a stunted child ranged from 1-7 to 7-8. In a review of early nutrition and later-life, adiposity and high birth weight was associated with subsequent obesity, whereas the evidence for poor nutrition in early life as a risk factor for increased fatness later in life was inconclusive. In a more recent review, the increase in weight or BMI and rapid growth during infancy were associated with obesity in childhood and adulthood.
In Brazil, stunted boys accumulated more body fat and gained less lean mass than non-stunted boys, and stunted girls showed a significantly higher percentage of fat mass at the end of follow-up, whereas non-stunted girls showed no significant differences in the percentage of fat mass over time
In this study in British Journal of Nutrition ( Gigante et al 2007, 97, 949-954 ) a cohort of boys aged 18 years was studied in Pelotas. a city in Southern Brazil since their birth. The aim of the present analysis was to study the associations between stunting, wasting and underweight at 2 and 4 years of age, and the body composition of male adolescents. This is part of a long term study of boys identified at birth. It is note worthy that the population are boys. That 5% of the group died and those who were poor, with low birth weight and malnourished were most at risk.
The conclusions of this study which included body composition indices was that under nutrition in early life is not a risk facto for over weight or obesity. These boys had lower fat, lean and body mass indices.
The results suggest that under nutrition is not a risk factor for overweight and obesity in later life population and may partially protect against fatness in adolescence.
This is a remarkable study and illustrated the merit of long term studies.

A sad end to a goat "wife"

A sad story.
Rose a Sudanese goat had been the focus of world wide interest since the report in the Juba Post in 2004 that she was forced into marriage with a Sudanese man. The forced marriage was the result of an intemperate relationship between a man who was drunk (so he claimed ) and the goat. To preserve Rose’s reputation the man was obliged to pay a dowry to the owner and “marry “the goat.
Everyone expected the happy couple to live happily ever afterwards. There are 178,000 returns for Google for “goat, Sudan, Marry “.

However the value of a varied balanced diet, even for a goat, was underlined when Rose died after swallowing and choking on a plastic bag as she scavenged for food scraps on the streets of Juba.
She left a grieving kid and the unrelated widow.
Times London Friday May 4th 2007

Receptors for bitter taste

The sense of taste provides animals with valuable information about the nature and quality of food. When animal experience a bitter taste this is a warning against the ingestion of toxic and noxious substances. . The mechanism of this is through bitter taste receptors called T2Rs.The T2Rs are a family of approximately 30 different G-protein-coupled receptors (GPCRs) that are selectively expressed in the tongue and palate epithelium. Differences in T2Rs between species (human and mouse) can determine the selectivity of bitter taste responses. ( Mueller et al Nature 2005, 10th March vol 434 pp 225-9
Mice and humans have distinctive differences in their sensitivities to many bitter compounds
In mice (m)T2R5 is a high affinity receptor for cycloheximide (Cyx)
In humans (h)T2R16 is a receptor for (3-glucopyranosides (salicin and related compounds),
( h)T2R14 is a candidate receptor for picrotoxinin
(h)T2R44 and (h)T2R61/hT2R43 are receptors for denatonium, aristolochic acid and 6-nitrosaccharin
Several β-glucopyrano-sides evoke strong bitter taste in humans, yet mice are largely indifferent to these compounds
. Similarly, phenylthiocarbamide (PTQ, a well known bitter taste often used in human genetic studies, is ineffective in mice.
Mueller et al were able to confer human bitter taste responses on mice by introduction of human taste receptors.
.From Mueller et al Nature 2005, 10th March vol 434 pp 225-9

Salt and cardiovascular disease.

Blood pressure is the most important factor in the development of strokes and other cardiovascular diseases. The dietary intake of salt(sodium chloride) has a role in determining blood pressure and hypertension . This is well shown in clinical trials. This finding applies regardless of age, gender, ethnic origin, base line blood pressure and body mass.
Salt intake is a good predictor of the incidence of cardiovascular events.
There have been few studies on the benefits of reduced salt intake on clinical outcome as opposed to reducing blood pressure.
Cook and colleagues (BMJ 2007, vol 334, 885-8), now show the long term benefits of reduced dietary sodium on cardiovascular disease in people participating in controlled randomised trials of hypertension prevention and follow-up studies . More than 3000 participants without hypertension were randomised to a reduced sodium intake for 18 months or to a control arm. The reductions in sodium intake were 44 mmol/day and 33 mmol/day ( 2.6 and 2.0 g of salt), respectively. The results show that people originally allocated to either sodium reduction group had a 30% lower incidence of cardiovascular events in the next 10-1.5 years, irrespective of sex, ethnic origin, age, body mass, and blood pressure.
In 1985, the World Health Organization recommended that the average salt intake should be reduced to 5g per day or less. However, few countries- have policies for targeted reduction in salt intake.
In Westernised countries, people derive salt mostly from bread and processed food and only a small proportion comes from added salt. Any reduction therefore needs the involvement of the food industry.
In many developing countries, like those of sub-Saharan Africa, where the main source of salt is still added salt ,there should be a place for education
Cook et al BMJ 2007, vol 334, 885-8
Cappuccio BMJ 2007, vol 335, pp 859-60