nutritional supplements use and contamination with doping agents.

Nutritional supplements: prevalence of use and contamination
with doping agents
In a review article by van Thurne and colleagues they discuss the role that nutritional supplements play in the lifestyle of a substantial proportion of the population
In addition to vitamins or minerals products, several precursors of anabolic steroids are marketed as nutritional supplements. Another group of commercially available supplements are products for weight loss based upon herbal formulations originating from Ephedra species.
Whilst some supplements indicate the presence of these active compounds, numerous non-hormonal nutritional supplements are to be found that were contaminated with non-labelled anabolic steroids. Stimulating agents other than naturally occurring analogues of ephedrine were detected
A major group using dietary supplements are sportsmen, ranging from amateur level to elite athletes. Besides the possible health risks associated with the use of dietary supplements, athletes should take care not to violate the rules of the World Anti-Doping Agency
The responsibility for knowing what is in these supplements lies with athletes. They remain responsible for substances detected in their biofluids, irrespective of their origin.
The consequences of failing to do this are dire. The drug testing system is now very efficient. Or appears to be.
W. Van Thuyne et al 2006, Nutritional supplements:prevalence of use and contamination with doping agents. Nutrition Research Reviews vol 19 , 147-158

a good text on thermodynamics

Peter Atkins has written a non mathematical book on thermodynamics.
To my mind there are three elements to nutrition.
1. What goes into the system ( food)
2. How the food is metabolised ( metabolism and thermodynamic)
3. What happens to the metabolic process e.g. growth , exercise etc
Whilst much attention is given to 1 and to an extent 3 few in Nutrition with note worthy heroes cope with 2
The reason is simple we who are attracted to nutrition are not attracted to the subject because of its mathematical content. Quite the converse. Most of our maths is restricted to counting calories.
But thermodynamics are to be neglected at our peril
The underlying problems will be resolved by an understanding of the thermodynamics of the obese system.
Or maybe obesity is some form of infection rather as duodenal ulcers turned out to be not due primarily to acid but the Helicobacter bacteria. .
The book which is well recommended is
Four laws that drive the universe Peter Atkins Oxford University Press

good practical slimming advise

I bought a sandwich from BON APPETIT and found this advise on how to slim. It was such common sense that I thought it was worth handing on. I have not contacts with the firm and only occasionally eat sandwiches but this is such good advise.
EAT WITH YOU& HEAD
They interviewed loads of French women (of all ages). A few Spanish and a couple of Italians as well. Here’s their advice on eating well (and keeping a good figure):

Insist on nutritious, fresh, natural, quality food without any nasties in it

Eat three times a day and don’t pig out No grazing Don’t count calories.

Simply eat with your head. Think about what your’re eating (before you eat it]

Lay the table, sit down, get a plate. And when you’re nearly full, stop eating

Don’t diet , diets are rubbish. Being on a diet is a constant losing bottle

Crisps, cookies and candy are not ‘treats’. Eat them at your peril

Drink lots and lots (and lots) of water every day and, dare we say it, less alcohol?

If you hate exercise don’t worry (don’t feel guilty).

Eat and drink properly and you’ll be fine

Behave slim and you’ll stay slim. Slim is a state of mind

from a sandwich box sold by BON APPETIT

a new dimension to RNA, small RNA

A new development in our understanding of metabolism as controlled by our genome is the finding of a large family of small non coding RNAs.
In a clear summary in Nature Grobhans and Filopwicz explain their biology
There arc three main types of well characterised RNA:
Messenger RNA, transfer RNA and ribosomal RNA.
Messenger mRNAs are translated into proteins, whereas transfer tRNAs and ribosomal rRNAs have housekeeping roles during mRNA translation
Small RNAs (20-30-nucleotides) are not translated into proteins, but regulate biological processes, often by interfering with mRNA translation.
Small RNAs include small interfering RNAs (siRNAsJ, microRNAs (miRNAs) and Piwi-associated RNAs (piRNAs).

A summary of RNAs

Messenger RNAs (mRNAs) act as templates for protein synthesis.

Ribosomal RNAs ( rRNAs ) are found in ribosomes, and mediate the decoding of mRNAs to the amino-acid sequences of proteins.
Transfer RNAs (tRNAs ) carry individual amino acids to the site of protein synthesis that recognize specific codons in -mRNA.
Non-coding regulatory RNA
Small interfering RNAs ( siRNAs)
Small RNAs (20-25 nucleotides in length)are formed by cleavage of long double-stranded RNA molecules. These are important in modulating of transposons activity and combating viral infection, and regulate protein-coding genes
.MicroRNAs (miRNAs) Small RNAs (20-25 nucleotides in length) are encoded by specific genes from long, single-stranded RNA sequences and fold into hairpin structure. The are important in repressing mRNA translation or mRNA degradation
Piwi-associated RNAs (piRNAs ) are small RNAs (25-3nudeotides in length) and are essential for the development of germ cells.
Longer non-coding RNAs of of 70 to thousands of nudeotides lengths which are involved in various cellular processes, including mRNA splicing and ribosome biogenesis.
Small RNAs are generally produced by fragmentation of longer precursors eg from double-stranded RNAs form ed by base-pairing of complementary RNAs by the enzyme Dicer into shorter double-stranded siRNAs some 20 base pairs long.
Each strand assembles into an effector complex known as an RNA-induced silencing complex (RISC), finds a mRNAs with a sequence perfectly complementary to the siRNA. RISC then cleaves the mRNA in the middle of the mRNA-siRNA duplex, and the resulting mRNA halves are degraded by other cellular enzymes
MicroRNAs are processed from specific genome-encoded precursors, in two steps, catalysed by the enzymes Drosha (in the nucleus) and Dicer (in the cytoplasm).
Piwi associated RNAs are generated from long, single-stranded precursors in a process independent of Drosha and Dicer. There are tens of thousands of these and are important in the development of the germ cell.
Grobhans and Filipowicz 2008 The expanding world of small RNAs vol 451, 414-416

prion detection

Prion infection is a worry with beef in the human food chain. This rather
esoteric paper is an important step in the detection of this threat to human
well being.,

Privat et al 2008 Human prion diseases: from antibody screening to a standardized
fast immunodiagnosis using automation. Modern Pathology vol 21, 140-149

Demopstration of pathological prion protein accumulation in the central nervous system is required to establish the diagnosis of transmissible subacute encephalopathies. In humans, this is frequently achieved using prion protein immunohistochemistry in paraffin -embedded tissue, a technique that requires multiple epitope retrieval and denaturing pretreatments. In addition to being time-consuming this procedure induces tissue alterations that preclude accurate morphological examination. The aim of the study described in this paper was to simplify prion protein immunohistochemistry procedure in human tissue, together with increased sensitivity and specificity. A panel of 50 monoclonal antibodies were produced using various immunugens ( human and ovine recombinant prion protein, prion protein peptides. denatured scrapie associated fibrils from 263K-infected Syrian hamsters) and directed against different epitopes along the human prion protein sequence. A panel of different forms of genetic, infectious and sporadic transmissible subacute encephalopathies was assessed. The monoclonal 12F10 antibody provided a high specificity and fast immunodiagnosis with very limited denaturing pretreatments. A standardized and reliable fast imnmnostaining procedure was established using an automated diagnostic system and allowed prion protein detection in the- central nervous system and in tonsil biopsies. It was evaluated in a series of 300 patients with a suspected d iagnosis of transmissible subacute transmissible encephalopaties and showed high sensitivity.

lipid update

I was trained a s a lipid chemist and have always enjoyed this aspect of biochemistry, along with the analytical techniques and function studies. A series of reviews in Nature Reviews Molecular Cell Biology are hence very interesting to me. The place of nutrition in these stories is through the building blocks which is so important.
Mark A. Lemmon 2008, Membrane recognition by phospholipid-binding domain Nature Reviews Molecular Cell Biology vol 9 pp99-111
Many different globular domains bind to the surfaces of cellular membranes, or to specific phospholipid components in these membranes. This binding is often tightly regulated. Examples include pleckstrin homology and C2 domains, which are among the largest domain families in the human proteome. Crystal structures, binding studies and analyses of sub cellular localization have provided much insight into how members of this diverse group of domains bind to membranes, what features they recognize and how binding is controlled. A full appreciation of these processes is crucial for understanding how protein localization and membrane topography and trafficking are regulated in cells-
Hannun and Obeid 2008 Principles of bioactive lipid signalling: lessons from sphingolipids Nature Reviews Molecular Cell Biology vol 9 pp 139-50
It has become increasingly difficult to find an area of cell biology in which lipids do not have important, if not key, roles as signalling and regulatory molecules. The rapidly expanding field of bioactive lipids is exemplified by many sphingolipids, such as ceramide, sphingosine, sphingosine-1-phosphate . ceramide-1-phosphate and lyso-sphingomyelin, which have roles in the regulation of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intraccllular trafficking. Deciphering the mechanisms of these varied cell functions necessitates an understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action.
Michell 2008 Inositol derivatives: evolution and functions. Nature Reviews Molecular Cell Biology vol 9, 151-161
Current research on inositols mainly focuses on myo-inositol derivatives in eukaryotic cells, and in particular on the many roles of myo-inositol phospholipids and polyphosphorylated myo-inositol derivatives. However, inositols, and their derivatives are more versatile than this — they have acquired diverse functions over the course of evolution. Given the central involvement of primordial bacteria and archaea in the emergence of eukaryotes, what is the status of inositol derivatives ini these groups of organisms, and how might inositol, inositol lipids and inositol phosphates have become ubiquitous constituents of eukaryotes? And how, later, might the multifarious functions of inositol derivatives have emerged during eukaryotc diversification?
See what I mean?

apoptosis and cancer

Letai (2008) Diagnosing and exploiting cancer's addiction to blocks in apoptosis Nature Reviews Cancer H, 121-132
Apoptosis is an important bodily function, but the control of which has yet to be associated with nutrition.
Cancer cells survive despite violating rules of normal cellular behaviour that ordinarily provoke apoptosis. The blocks in apoptosis that keep cancer cells alive are therefore attractive candidates for targeted therapies. Recent studies have significantly increased our understanding of how interactions among proteins in the BCL2 family determine cell survival or death. It is now possible to systematically determine how individual cancers escape apoptosis. Such a determination can help predict not only whether cells are likely to be killed by antagonism of BCL2, but also whether they are likely to be sensitive to chemotherapy that kills by the intrinsic apoptotic pathway.

Adding fluoride to water supplies

Adding fluoride to water supplies.
This is such a contentious subjects. The observation that towns in the North East of England which were close together had different teeth decay levels lead to the observation that the fluoride content of the drinking water was the determinant.
The next step was to fortify the drinking water of fluoride deficient water. ( Germany, Ireland, Portugal, Spain, UK and USA) or table salt ( France ). Water fluoridation is intended to reduce social inequality in the provision of fluoride.
There has been much debate on this subject which has generated heat and dismay. Is this mass medication or acting within commonly found natural limits. If a medicine then the standard of proof has to be that of a medicine.
In the BMJ this topic has been reviewed
Cheng, Chalmers, Sheldon ( 2007 ) Adding fluoride to water supplies BMJ vol 335, 699-702
A review commissioned by the Department of Health in England at the University of York looked at the evidence for benefit of adding fluoride to drinking water on dental health. Whilst there are many papers on this subject many did not meet proper scientific standards.
A problem is fluorosis, teeth mottling which was visible in 48% and aesthetically concerning in 12% of people studied at 1 part per million.
A claim for an increase in bladder cancer from Taiwan proved to be a difficult one to prove or disprove and the evidence is at the best marginal.
Studies become more difficult because of the wide availability of fluoride containing toothpastes. The benefit in young children appears to be 24%.
Fluoride is the main factor that alters the resistance of teeth to acid attack and sugar in plaques. Caries are reduced fluoride which
Reduces and inhibits the dissolution of enamel
Promotes remineralisation
Alters the ecology of the plaque.

Fluoride is most effective when used topically


.

The effectiveness of encouraging exercise in children

The BMJ of 6th October has two interesting articles on trying to encourage the young to take exercise.
Exercise is a key contributor to weight and the more exercise the better.
However one’s experience is that children vary so much in how much they exercise. There was a time when the young would walk to school and there were physical education classes and games. This is no longer the case.
Even in games there is variation. On a professional football pitch, there are those who run several mile s and others like the goal keeper and the strikers who may cover a much shorter distance.
Improvement in exercise is hard to assess but there must be a difference between a statistically positive improvement and an improvement which is sustained and which improves weight and health and is regarded as fun. In the main article cited below there is a failure to identify the amount of exercise actually needed. The increases ranged from the trivial 3 minutes to 50% increase.
Also a child who hates organised sport may love swimming and dancing.
The conclusions in these articles are full of hope but enable to identify how to evaluate success.
This is a really good area for work, including the inner cities.
Giles-Corti and Salmon -Leader BMJ 2007 Encouraging children and adolescents to be more active BMJ vol 335 pp 677-8#
Sluiijs et al 2007 Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials. BMJ vol 335, 703-7

Managing liver dysfuntion in parenteral nutrition

David A. J. Lloyd and Simon M. Gabe 2007 Managing liver dysfunction in parenteral nutrition, Proceedings of the Nutrtion Society vol 66 530-538
Parenteral nutrition is such a help in the compromised patient. When I ran the TPN service in the Hospital where I worked live abnormalities were a constant problem . So I found this article very interesting.
Parenteral nutrition is life saving in patients with intestinal failure but liver dysfunction is a frequent problem , especially in neonates. Although abnormal liver function tests associated with short-term parenteral nutrition are usually benign and transient, liver dysfunction in both children and adults receiving long-term parenteral nutrition can progress to end-stage liver disease and liver failure. The aetiology of parenteral nutrition-associated liver disease is com­plex and multi factorial, with a range of patient, disease and nutrition-related factors implicated. Sepsis is of particular importance, as is the lack of enteral nutrition and overfeeding with intravenous glucose and/or lipid. Deficiencies of a number of amino acids including cholinc and taurine have also been implicated. Management of hepatic dysfunction in parenteral nutrition should initially focus on preventing its occurrence. Sepsis should be managed appropriately, enteral nutrition should be encouraged and maximised where possible and parenteral overfeeding should be avoided. Provision of parenteral lipid should be optimised to prevent the adverse effects of both deficiency and excess, and cyclical rather than continuous parenteral feeding should be administered. There is some evidence of benefit in neonates from oral antibiotics to prevent intestinal bacterial overgrowth and from oral ursodeoxycholic acid, but less to support their use in adults. Similarly, data to support widespread use of parenteral choline or taurine supplementation are lacking at present. Ultimately, severe parenteral nutrition-associated liver disease may necessitate referral for small intestine and/or liver transplantation.

influence of sleep on food intake and metabolism

Crispim et al , 2007 The influence of sleep and sleep loss upon food intake and metabolism Nutrition Research Reviews vol 20 195-212
This review looks at the role of sleep and its alteration in influencing metabolic disorders. A reduction in the amount of time spent sleeping has become an endemic condition in modern society. There are important associations between sleep loss and alterations in nutritional and metabolic aspects.
Some studies suggest that individuals who sleep less have a greater probability of becoming obese. This may be related to an increase of ghrelin and decrease of leptin concentrations and an increase of appetite and hunger
Sleep loss has been closely associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and diabetes, and this disturbance may reflect decreased efficacy of the negative-feedback regulation of the hypothalamic- pituitary -adrenal axis.
During of sleep there is also an increase in blood lipid concentrations, which can be be more pronounced with reduced sleep time, leading to disorders in fat metabolism.
The authors conclude sleep loss represents an important risk factor for weight gain, insulin resistance, type 2 diabetes and dyslipidaemia.
Therefore, an adequate sleep pattern is fundamental for the nutritional balance of the body and should be encouraged by professionals in the area.
It does of course matter why there is sleep loss. There is a difference between an active social night life sleep loss and anxiety induced sleep loss and consequent metabolic problems.

zeaxanthins and lutein and age related macular eye disease.

Thurnham has written a very interesting review of macular zeaxanthins and luteins.
Thurnham (2007) Macular zeaxanthins and luteins-a review of dietary sources and bioavailability and some relationship with macular pigment optical density and age-related macular disease. Nutritional Research Reviews vol 20 163-179.

The retina is unique in the human body in containing three xanthophyll carotenoids: 3K,3'R-zeaxanthin. meso-zeaxanthin (MZ) and lutein.
We eat 1 to 3 mg lutein per day and the lutein: zeaxanthin ratio in the diet is about 5:1 .Xanthophyll pigments occur widely in vegetables and fruits but MZ is found in only a few foods such as the shrimp carapace and fish skin.
In spite of the amounts of the different xanthophylls in the diet, zeaxanthin and MZ occur in approximately equal amounts in the eye, and their combined concentration can exceed that of lutein. A number of studies have used single and mixed sources of the pure xanthophylls to achieve steady-state plasma responses. Mostly these have been with lutein and zeaxanthin but two using MZ are also described.
Vegetables are the richest source of dietary lutein Intervention studies with eggs, which are a good source of zeaxanthin. suggest that the xanthophyll carotenoids in egg yolk may be more bioavailablc than those in other foods
Very limited information from human studies of MZ-containing supplement. suggests that MZ is less well absorbed than zeaxanthin. Thus plasma responses may not reflect true absorption if it takes MZ longer to equilibrate with body tissues than the other xanthophylls and competition with zeaxanthin may lower the relative concentrations of MZ in plasma.
It would be nice if a xanthophyll carotenoids rich diet kept the retrina healthy, but this has yet to be proven

Inter action nitrogen and carbon cycles

The acceleration of the nitrogen cycle as a result of the production and industrial use of artificial nitrogen fertilizers worldwide has enabled human kind to increase food production. However there are unforeseen environmental problems.
Studies on these alterations in the nitrogen cycle have led to a much improved understanding of the scope of the problem and possible strategies for managing it. These alterations in the nitrogen cycle affect other major biogeochemical cycles, particularly that of carbon.
The release of carbon dioxide (CO2) from the burning of fossil fuels has major consequences for the functioning of the global carbon cycle, and as nitrogen has a crucial role in controlling key aspects of this cycle, the nitrogen-carbon-climate interactions are becoming increasingly pressing.
Does the availability of nitrogen affect the capacity of Earth's biosphere to continue absorbing carbon from the atmosphere, and hence continue to help in mitigating climate change. The dynamics of the nitrogen cycle are important in the context of a changing carbon cycle, a changing climate and changes in human actions.
Nitrogen is a fundamental component of living organisms; but is in short supply in forms that can be assimilated by plants in both marine and land ecosystems. Nitrogen has a critical role in controlling primary production in the biosphere. Nitrogen is also a limiting factor for the plants grown by humans for food. Without the availability of nitrogenous fertilizer produced by the Haber-Bosch process, the enormous increase in food production over the past century, which in turn has sustained the increase in global population, would not have been possible. All the nitrogen used in food production is added to the environment, as is the nitrogen emitted to the atmosphere during fossil-fuel combustion.
In the 1990s, these two sources of anthropogenic nitrogen to the environment amounted to more than 160 teragrams (Tg) N per year On a global basis, this is more than that supplied by natural biological nitrogen fixation on land (HOTg N per year) or in the ocean (UOTgN per year}.
Given expected trends in population, demand for food, agricultural practices and energy use, anthropogenic nitrogen fluxes will increase; that is, humans are likely to be responsible for doubling the turnover rates not only of the terrestrial nitrogen cycle but also of the nitrogen cycle of the entire Earth.
The negative consequences of these nitrogen additions include excessive growth of plant and microorganisms in terrestrial and aquatic systems to global acidification and stratospheric ozone loss
Also chemical transformations of nitrogen along its transport pathway in the environment is important. Nitrogen oxide can first cause photochemical smog and then, after it has been oxidized in the atmosphere to nitric acid and deposited on the ground, can lead to soil and water acidification and excessive growth of plant and microorganisms
The human acceleration of the nitrogen cycle did not occur, alone as the phosphorus, sulphur and carbon cycles are are affected. The burning of fossil fuels and carbon emissions from land-use change, atmospheric CO, has increased to levels that are more than 30% above those of pre-in Industrial times and the observed warming over the past century, particularly that of the past 30 years.
The perturbations of the global nitrogen and carbon cycles caused by human activity are in part linked to each other. This is mostly a result of the atmosphere's being very efficient in spreading the nitrogen oxides and ammonia emitted as a result of energy and food production, and also because this nitrogen is deposited on the ground in a form that is readily available to plants, thereby stimulating productivity and enhancing the uptake of CO, from the atmosphere
The deposition of both nitrogen products and carbon in the oceans has unknown effects.
Gruber and Galloway 2008 An earth-system perspective of the global nitrogen cycle . Nature vol 451, 293-296

Maternal and childhood malnutrition 1

The Lancet has embarked on an immensely important series on Maternal and Childhood under nutrition s
BlackRL et al 2008, Maternal and child undernutrition: global and regional exposures and health consequence. The Lancet vol 371, 243-260.
There are also important leaders in the same edition
Morbidity and mortality in families in Iraq p177
Maternal health and child undernutrition: an urgent opportunity R Horton p 179
The challenge of hunger J Sheeran p 180
Nutrition interventions need improved operational capacity Heikens et al p 181

Maternal and child undernutrition is highly prevalent in low-income and middle-income countries, resulting in substantial increases in mortality and overall disease burden. In this paper, new analyses are presented to estimate the effects of the risks related to measures of undernutrition, as well as to suboptimum breastfeeding practices on mortality and disease
They discussed their findings as
Maternal short stature and low body mass index in pregnancy and lactation. Maternal short stature is a risk factor for mother and baby in the delivery as the pelvis is small.
Childhood underweight, stunting and wasting.
The authors estimate that stunting, severe wasting, and intrauterine growth restriction together were responsible for 2 2 million deaths and 21% of disability-adjusted life-years (DALYs) for children younger than 5 years. Deficiencies of vitamin A and zinc were estimated to be responsible for 0 6 million and 0 4 million deaths, respectively, and a combined 9% of global childhood DALYs. Iron and iodine deficiencies resulted in few child deaths, and combined were responsible for about 0 2% of global childhood DALYs. Iron deficiency as a risk factor for maternal mortality added 115000 deaths and 0 4% of global total DALYs. Suboptimum breastfeeding was estimated to be responsible for 1 - 4 million child deaths and 44 million DALYs (10% of DALYs in children younger than 5 years). In an analysis that accounted for co-exposure of these nutrition-related factors, they were together responsible for about 35% of child deaths and 11% of the total global disease burden. The high mortality and disease burden resulting from these nutrition-related factors make a compelling case for the urgent implementation of interventions to reduce their occurrence or ameliorate their consequences.
Maternal and child undernutrition is the underlying cause of 3-5 million deaths, 35% of the disease burden inchildren younger than 5 years and 11% of total global DALYs
The number of global deaths and DALYs in children less than 5 years old attributed to stunting, severe wasting,and intrauterine growth restriction constitutes the largest percentage of any risk factor in this age group
Vitamin A and zinc deficiencies have by far the largest remaining disease burden among the micronutrientsconsidered
Iodine and iron deficiencies have small disease burdens, partly because of intervention programmes, but sustained effort is needed to further reduce their burden
Sub optimum breastfeeding, especially non-exclusive breastfeeding in the first 6 months of life, results in
1-4 million deaths and 10% of disease burden in children younger than 5 years
Maternal short stature and iron deficiency anaemia increase the risk of death of the mother at delivery accounting for at least 20% of maternal mortality

Global Food Chain

Nutrition on a macro scale is a compelling subject. The Television News frequently carries pictures of awful deprivation. A recent radio programme spoke of the horrors of the famine around Calcutta in India during the second World War when millions died.
Raj Patel has written a timely book
Stuffed and Staved: Markets , power and the hidden battle for the World’s food system. Portobello Books
He discusses the food chain . He emphasises the importance of our relationship with the land and the natural world. Global warming, in part, is the consequence of ignoring this.
Coupled to the excess number of humans alive today. Yet who can deny each individual their life
This very important book is reviewed in the Lancet 2007 vol 370 pp2089-90 by . Jonathan Porrit. Even if you don’t get the book at least try to read this captivating review.

Vitamin D in Health and illness

Vitamin D health and illness.
Susan Mayor in the BMJ 12 JANUARY 2008 VOLUME 336 page 62

Vitamin D deficiency is associated with bone disease .
Two recent studies show that lack of the vitamin D also increases the risk of heart disease and is linked to poorer prognosis for some cancers.
A follow-up study of 1739 offspring of the original participants in the Framingham heart study, with no cardiovascular disease, showed that those with low concentrations of vitamin D (below [5 ng/ml) had twice the risk of a first cardiovascular event, such as a myocardial infarction, heart failure or stroke, over a five year period than those with higher concentrations Wang et al in Circulation. After adjusting for the usual cardiovascular risk factors, high cholesterol concentrations, diabetes, and hypertension, the risk of a cardiovascular problems remained 62% higher in people with low vitamin D concentrations
A second study by Moan et al in Proceedings of the National Academy of Sciences of the United States of America shows that warnings to avoid sunlight because of the risk of skin cancer from solar radiation may have to be balanced against the health benefits of exposure to sunlight, given that vitamin D improves outcomes in patients with major internal cancers, including prostate, breast, and colon cancers.
The study showed that vitamin D production generated by solar radiation was 3.4 times greater in countries south of the equator than in the United Kingdom and 4.8 times greater than in Scandinavia. Although the incidences of major internal cancers were higher in countries at lower latitudes, the survival prognosis improved significantly.
Wang et al Vitamin D Deficiency and Risk of Cardiovascular Disease.
Circulation. 2008 Jan 7;
Moan, et al 2008 Addressing the health benefits and risks, involving vitamin D or skin cancer of increased sun exposure. Proceedings of the National Academy of Sciences of the United States of America vol 105: 668-673;
It would be an interesting thought that the absence of heart disease and cancer attributed to dietary fibre was in part a consequence of sun light and vitamin D production.

Marathon running and sudden deaths

Exercise is an integral element in the advise for a healthy and long life. There are those , including myself who love running and run or ran marathons.
The distance is considerable and the training demanding. People die on such runs.
It is therefore interesting to read a paper which studies marathon running and the chances of sudden death.
Redelmeir and Greenwald looked at the risk of sudden cardiac death associated with running in an organised marathon compared with the risk of dying from a motor vehicle crash that might otherwise have taken place if the roads had not been closed.
They looked at Marathons with at least 1000 participants that had two decades of history and took place on public roads in the United States, 1975-2004.
The marathons provided results for 3,292,268 runners on 750 separate days about 14 million hours of exercise.
There were 26 sudden cardiac deaths observed, equivalent lo a rate of 0.8 per 100000 participants. Because of road closure, an estimated 46 motor vehicle fatalities were prevented, equivalent to a relative risk reduction of 35%. The net reduction in sudden death during marathons amounted to a ratio of about 1.8 crash deaths saved for each case of sudden cardiac death observed (95% confidence interval: 0.7 to 3.8). The net reduction in total deaths could not be explained by re-routing traffic to other regions or days and was consistent across different parts of the country, decades of the century, seasons of the year, days of the week, degree of competition, and course difficulty. So organised marathons are not associated with an increase in sudden deaths from a societal perspective, contrary to anecdotal impressions fostered by news media.
Redelmeier and Grenwald 2007 Competing risks of mortality with marathons: retrospective analyis BMJ . vol 335, 1275-7

Curcumin and gastrointestinal cancer.

In the Newsletter published by the American Gasttoenterology Association there is an interesting article by Kunnumakkara and Aggarwal ( AGA perspectives vol 3 issue 6 pp8-10 )
The write of the belief that sporadic cancers are preventable especially gastrointestinal cancers. To support this belief
Gastrointestinal cancers are more common in developed countries than in developing countries. The incidence of colorectal cancer in India is less than a tenth that in the U.S.
Grilled meal and fried foods, environ­mental pollutants, and certain viruses and bacteria have been linked to tumoro-genesis of the GI tract in rodent models.
Dietary components derived from fruits and vegetables have been shown to suppress carcinogenesis in animals.
Epidemiological studies and limited clinical trials in humans suggest a role for fruits and vegetables in the prevention of GI cancers.
The foods and the active agents that have been so far linked with prevention of GI cancers include resveratrol from grapes, peanuts and berries; catechins from tea; genistein from soybean; caffeic acid from mustard seeds, olive oil from olives; curcumin from turmeric; quercetin from onions; ellagic acid from pomegranate; diallyl disulfide from garlic; sulforaphane from broccoli; lycopene from tomato; and indoIe-3-carbinol from cruciferous vegetables .
These agents may have protective effects against GI cancers by targeting multiple molecular targets.
Curcumin gives curry powder (turmeric) its yellow colour, and is the dietary agent which the authors know most with respect to GI cancers. Its active ingredient is diferuloylmethane. Curcumin has been shown to protect animals from a wide variety of carcinogens that cause GI cancers .
A protective effects of curcumin have also been reported in patients with Crohn's disease, ulcerative colitis, irritable bowel disease (IBS) and tropical pancreatitis).
The mechanisms mediating the inhibitory effects of curcumin have been extensively investigated. Their group showed that curcumin down-regulates the activation of NF-kB, leading to down-regulation of anti-apoptoric, cell proliferative, invasive and angiogenic gene products.
Curcumin also suppresses the activation of STAT3 HIF-1 and PPAR-y. Curcumin down-regulates the activity and expression of both COX2 and 5-LOX , down-regulates the expression of TNF,ILl.-l and IL-6; and inhibits EGF receptor signalling. In spite of interfering with all these targets, curcumin has been found to be pharmacologically safe at very high doses, with no dose-limiting toxicity.

I have always been sceptical of comparisons of disease incidence between developed and developing countries. Many diseases so studied occur in an age group older than generally experienced in the developing world. It would also be possible to say that intestinal parasites, malaria and under nutrition may also protect.
Having said that this is serious and interesting work and offers great interest. Remember aspirin and its wide therapeutic value.

Dietary and life style advise , ancient and modern

Interesting and relevant dietary advise is available from the work of Kay-Tee Khaw and colleagues based at the University of Cambridge and the MRC Unit.
They questioned 20,000 healthy adults aged 45-79 about their life styles and measured their blood vitamin C concentration as a measure of fruit and vegetable intake.
They gave values between 0 and 4 for a series of healthy behaviours and then followed the participants for a period of time and recorded their death ( 0 being absence of a healthy behaviour, 4 being good )
People with low scores were much more liable to die of coronary heart disease than those with high scores. Low scorers were also liable to die 14 years earlier than those with high scores.
In order of impact the life style benefits in order best to least benefit, albeit still of benefit was
Not smoking
Eating fruit and vegetable
Moderate drinking and exercise.
It has long been known that smoking can educe life expectation by 11 years on its own
This was reported by Reuters and published in PLoS medicine.
In Melvin Bragg's BBC Newsletter 20th December he quotes Noga Arikha who has written a book
Passions and Tempers: a history of the humours, an ancient belief in medicine.

Each humour traditionally had specific characteristics, for instance:
Choler, or Yellow Bile
Predominant in those endowed with a choleric temperament
element: fire
qualities: hot and dry .
colour: yellow
taste: bitter .
season: summer
time of day: midday .
body organ: spleen .
period of life: youth .
signs: Virgo, Leo, Cancer .
planet: Mars
In a balanced person, the predominance of choler ensured a reactive and quick-tempered character. A choleric was typically able to make decisions well and fast, and preferred action over contemplation. But a surplus of choler could become "burned" and eventually turn into melancholy (melan=black, choler=bile, in Greek). Character could also become acrid and negative; reactivity might then be directed at the wrong objects. This sort of choleric could get angry easily and have episodes of uncontrolled, potentially dangerous rage. As Brutus exclaimed to Cassius in Shakespeare's Julius Caesar (IV, 3): "Must I give way and room to your rash choler? Shall I be frightened when a madman stares?
She does the same for melancholy and for blood and for phlegm.
This demonstrates that you had a life system through the four humours, giving your place in the universe, on the planet and inside your own skin.
Standard remedies for melancholia and other complaints included playing soothing music, taking baths, drinking broths and herbal infusions, applying leeches, and taking potions and pills - made with everything from mint and saffron to turpentine. Some of the remedies worked, others didn't and some had the opposite effect and ended up killing the patient."

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