five fruit and vegetables a day

The recommendation that we eat 5 different types of frit and vegetables a day is a real advance. I still worry though which 5 and how do we choose.
The range is wide
Nuts and seeds
Pulses
Grains and cereals
Leaf vegetables
Brassica
Pods and seeds
Shoot vegetables
Bulb vegetables
Root vegetables
Tubers
Fruit vegetables
Cucumbers and squashes
Mushrooms and truffles
Sea vegetables
Apples, pears and grapes
Pitted fruit
Berries and soft fruit
Tropical and exotic fruit
Melons
Citrus fruit
Herbs
Spices
And that is a cookery book classification not botanical.
I think this is a challenge for nutrition research

Citation distortion in journals

This fascinating paper by Greenberg discusses the pattern of citations among papers stating belief in a particular scientific phenomenon. He chose as his model the role of β-amyloid protein which is well known for its role Alzheimer’s disease but is also claimed to be produced and injure skeletal muscle fibres in inclusion body myositis.
Greenberg looked at 242 papers and 675 citations with looked at this with a devise called social network theory and graph theory.
Of the 10 authoritative papers which provided experimental evidence supporting the concept of inclusion body myositis muscle fibres, four provided experimental data and were from the same laboratory. Six papers refuted the claim. The 4 papers supporting the claim received 94% of the subsequent citations and the refuters 6 %. Some other papers had data, which failed to show the phenomenon, but claimed this supported the claim.
I am aware of this because a widespread claim that it is possible to heat water for domestic use using a compost heap traces to one paper, with a huge compost heap which worked briefly.
Greenberg 2009 How citation distortion create unfounded authority: analysis of a citation network. BMJ vol 339 pp 210-213

Food balance sheet and epidemiology

Worldwide dietary data for nutrition monitoring and surveillance are commonly derived from food balance sheets (FBS) and household budget surveys (HBS). This is important as specifically designed individual nutrition surreys are both expensive and labour intensive and require skill and co-operation.
In this huge study Naska et al have compared food supply from FBS and food availability data from HBS among eighteen European countries and have estimated the extent to which they correlate, focusing on food groups which are comparably captured by FBS and HBS and for which there is epidemiological evidence that they can have a noticeable impact on population mortality. Spearman's correlation coefficient was +0·78 (P< 10-3) for vegetables (including legumes), + 0·76 (P< 10-3) for fruits, +0·69 (P< 10-3) for fish and seafood and +0·93 (P< 10-3) for olive oil.
With respect to meat and meat products, the coefficient was lower at +0·39 (P=0·08).
The writers have examined whether the supply (FBS) or the availability (HBS) of food groups known or presumed to have beneficial effect on the occurrence of CHD and total cancer can predict overall, coronary and cancer mortality in ecological analyses. After controlling for purchasing power parity-adjusted gross domestic product and tobacco smoking we found that for vegetables, fruits, fish and seafood, as well as for olive oil, both the FBS and the HBS estimates were inversely associated with total mortality, coronary mortality and cancer mortality, although the number of countries with complete information on all study variables hindered formal statistical documentation (P>0·05 in some instances).
FBS and HBS have their own strengths and weaknesses, but they may complement each other in dietary assessments at the population level.

Naska et al 2009 Food balance sheet and household budget survey dietary data and mortality patterns in Europe. British Journal of Nutrition vol 102 166-171

The 500th blog

I think this is number 500 of these blogs. I do not know who, if any one, reads them but I enjoy looking at and recording different aspects of nutrition. I hope you enjoy the science of nutrition in all it exciting aspects.

Genomic copy number variation and human health.

Chromosomal structural abnormalities are now being studied as a result of the completion of the Human Genome Project. much of the structural variation in the genome has gone unrecognised until recently. Deletions and duplications of DNA strands of between a few hundred base pairs and several million base pairs (copy number variants) are widespread. Human genomic variation, as single nucleotide substitutions has been catalogued since the completion of the draft human genome sequence in 2000. The HapMap project, which by 2007 had documented more than 3 ·1 million single nucleotide polymorphisms (SNPs) and their inter-relation, has underpinned subsequent successful genome-wide association studies. Since 2007, genome-wide association studies based on single nucleotide polymorphisms show replicated associations to several common diseases. Some copy number variants explain rare, previously uncharacterised disorders, and they are now expected to explain some of the genetic contribution to common diseases. This review by Wain et al reviews current work to map copy number variants and discusses the of further understanding human health and disease.
Large deletions, duplications, and other structural rearrangements have a role in the aetiology of specific diseases (genomic disorders)
In addition intermediate scale structural variation, caused by a variable number of copies of a particular DNA segment are referred to as copy number variants. The influence of these on disease aetiology is now being studied.
The potential role of copy number variation in complex diseases, includes susceptibility to autism, shizophrenia, Crohn's disease, psoriasis," systemic lupus erythematosus. amyotrophic lateral sclerosis, and HIV-l . Such variation has also been associated with vertical transmission of HIV-l, and the progression and response to treatment of HIV-l/ AIDS.
Some of these associations could be false positives, others have had either technical validation or replication of findings in different study populations, or both. These validated associations are probably a direct or an indirect result of changes to the copy number of the relevant genomic sequence.
The location, size, and boundaries (breakpoints) of these variants documented in public databases have been very imprecise, although the new generation of maps of copy number variants are providing much improvement. Scalable methods to characterise copy number variation in association studies have been inexact. In this Review, Wain et al introduce copy number variation, examine advances in our understanding, and discuss the inferences that can be reasonably drawn from association studies of copy number variation.
Wain et al 2009genomic number variation, human health and disease. Lancet vol 374 pp 340-350

Evolution of Obesity

A recent book “The evolution of obesity” by Power and Schulkin is a very comprehensive survey of the possible causations of this complex problem. It identifies many weight-regulation mechanisms and possible evolutionary reasons for why these can fail. The book uses an evolutionary framework al to analyse a major body of neuroendocrine knowledge about obesity.
They point out that no simple description can be accurate.
Attributing one function to a hormone is attractive, but often wrong. There is a strong correlation of leptin concentrations with body-fat mass, suggesting that leptin limits body weight. But administering leptin to people who are obese does not reduce appetite or weight. Low leptin levels signal the need to seek food, but leptin is only one part of the complex system that regulates eating.
The authors come to similar conclusions for dozens of information molecules that are involved in feeding regulation - including the hormones ghrelin, corticotropin-releasing hormone and cholecystokinin.
The book covers nearly all the main issues in obesity research, the ‘thrifty genotype’ - shaped to store fat to cope with food scarcity , adipose tissue, where fat is stored, as an endocrine organ that secretes at least ten information molecules, and describe the role of cytokines as mediators of the tissue damage associated with abdominal obesity.
The epidemiology of the recent obesity epidemic, a threefold increase in obesity in the United States in just 50 years is discussed.
Power and Schulkin ask why humans eat meals instead of feeding continuously, quoting from explanations from behavioural ecology with the brain mechanisms responsible and with the social functions of sharing meals. They review changes in diet since the Palaeolithic era and the interactions between meat eating and brain evolution.
Other possible contributors to obesity are fructose-based beverages and exercise
The book is reviewed by Randolph Nesse in Nature 2009, vol 40 page 461
Power and Schulkin 2009. The evolution of obesity . John Hopkins University pp 408

newly discovered olfactory sensors

Mammals rely heavily on olfaction to interact adequately with each other and with their environment. The mammalian olfactory system recognizes diverse chemical stimuli conveying information about such things as food quality, the genetic identity or sexual status of potential mates, and even stress':'. A paper by Riviere et al in Nature May 2009 ) describes the identification of a chemosensory neuron in the rodent nose that responds to stimuli associated with cell damage, disease and inflammation, These results should help us to understand how animals identify pathogens or assess the health status of potential partners.
Until recently it was believed that the olfactory system of most mammals was of 2 types : a main olfactory system that detects environmental odours, for instance those emitted by food or predators, and an accessory (vomeronasal) olfactory system that detects pheromones - intraspecies chemical signals that elicit a stereotyped behavioural or hormonal change. It is now clear that the sense of smell is much more complex. Indeed, the main and accessory olfactory systems each respond to both general odours and pheromones.
Each olfactory division contains several types of sensory cell identified by the receptors and other proteins they express, the connections they make in the olfactory part of the brain, and the chemical stimuli to which they respond. This diversity of sensory cells in the nose has given rise to the concept of olfactory subsystems, each dedicated to a particular chemosensory role.
In addition animals use olfaction to assess whether other organisms may be dangerous, or even to judge the health status of potential partners. Mice use olfactory cues to avoid potential mates that are infected with parasites', whereas nematode worms develop aversions to odours given off by harmful bacteria, thereby avoiding toxic food, However, although such olfactory-based aversion behaviours have been documented, no olfactory subsystem that is dedicated to the assessment of health status or disease has been identified in mammals.
They make use of seven transmembrane G-protein-coupled receptors to identify odorants and pheromones. These receptors are present on dendrites of olfactory sensory neurons found in the main olfactory or vomeronasal sensory epithelia, and are involved in the odorant, trace amineassociated receptor and vomeronasal type 1 receptor superfamilies. The newly described formyl peptide receptor-related genes and vomeronasal sensory neurons, are found in multiple mammalian species. They are similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium.

Munger Noses within noses Nature vol 459, 521-2

Riviere et al 2009 Formyl peptide receptor – like proteins are a novel family of vomeronasal chemosensors Nature vol 459, 574-577

exercise for a small room

Exercise is good and can be a problem to do. The Royal Canadian Air force exercise regime is a superb way to exercise in a small space and 11 minutes a day can only be good.
There is a good article on this in FT com /weekend magazine July 18/19 pp 38-39 by Angus Watson

Exercise I

Stand with feet apart, arms up. Bend forward to touch the floor then stretch up

and bend backward. Do not strain to keep knees straight.

Exercise2
lie on your back with feet 6in apart. arms at sides. Sit up just far enough to see

your heels. Keep your arms straight. Your head and shoulders must clear the

floor.

Exercise 3

Lie on our front, palms placed under your thighs. Raise your head and one leg ,

repeating using alternative legs. Keep leg straight at the knee. Thighs must clear

palms.

Exercise 4

Lie on your front , arms under shoulders , palms flat on floor. Straighten arms and lift

upper body , keeping knees on floor. Keep body straight from knees, arms fully

extended . Chest must touch floor to complete one movement.

Exercise 5

Stationary run. Lift feet approximately 4 inches off the floor. Every 75 steps do 10

“scissors jumps ” : stand with right leg and left arm extended backward. Jump up and

change position of arms and legs before landing. Arms reach shoulder height.

Further details are available on the internet

Physical Fitness
Or www.gettingfitagain.com/5bx.php

cardiovascular disease prediction

The QRISK cardiovascular risk prediction was first published in 2007. The questionnaire predicts the chance of a cardiovascular event during the next 10 years. The questionnaire is available on the web and easily accessible through Google.
The questionnaire includes
Age, sex, systolic blood pressure, smoking status, serum cholesterol, : high density lipoprotein ratio, body mass index, family history of cardiovascular disease and social deprivation, and anti- hypertensive treatment. This questionnaire has been further validated in BMJ of 18th July 2009
Colins and Altman 2009 An independent external validation and evaluation of QRISK cardiovascular risk prediction: a prospective open cohort study. BMJ vol 339 pp 144-147.

protein diets and weight loss

In the management of obesity the effect of diet composition on feeding behaviour is clearly important to encourage weight loss in the short term and weight maintenance in the longer term. Isoenergetic amounts of the dietary macronutrients are not equal in terms of their effect on appetite and motivation to eat.
The diet composition strongly affects ad libitum energy intake with protein being the most satiating macronutrient, independent of energy density, relative to carbohydrate and fat. The protein-induced satiety is important as hunger is one of the main reasons why subjects do not comply with a weight-loss regimen .Are such diets safe ?.
For example, recent studies have indicated greater weight loss can be achieved on high-protein diets when compared with high-carbohydrate, low-fat alternatives for periods up to 6 months, but by 12 months, all diets were equally effective. However high-protein low-carbohydrate diets are high in fat, and often the contributions of fruit, vegetables and whole grains is low, which runs counter to current healthy eating advice. There is also some recent evidence that high-protein low-carbohydrate diets may have implications for gut health. But many studies show improvements in fasting lipidaemia and/or glycaemic control on such diets. High-protein diets could be a powerful tool to promote weight loss in the short term.
It is not known how much protein is required to maximise protein-induced satiety or whether there is a relationship with the energy density of the diet. Normal protein intake is about 15 % of energy intake, which, for a sedentary adult male, is approximately 76-88 g/d. The high-protein diets reported for weight-loss studies often include about 30 % of energy intake as protein. This does not mean that protein intake (g) is doubled, as energy intake is reduced. Often the protein intake is increased only by 30-40 % over habitual levels.
It is not clear if protein promotes satiety (inter-meal interval) or satiation (meal termination) or, indeed, both. Humans eat and over consume energy for a variety of reasons, often not related to hunger.
. Johnstone 2009 High-protein diets for appetite control and weight loss-the “holy grail “ of dieting British J of Nutrition vol 101 pp 1729-1730

Cancer genome

This is a fascinating review of the molecular biology of cancer by Stratton et al in Nature . . Cancer is responsible for one in eight deaths worldwide and includes more than 100 distinct diseases with diverse risk factors and epidemiology in most of the cell types and organs of the human body. The cancers are characterized by relatively unrestrained proliferation of cells that can invade beyond normal tissue boundaries and metastasize to distant organs.
There is a central role of the genome in cancer development and bizarre chromosomal aberrations. Agents that damage DNA and generate mutations also cause cancer. Subsequently, increasingly refined analyses of cancer cell chromosomes showed that specific and recurrent genomic abnormalities, such as the translocation between chromosomes 9 and 22 in chronic myeloid leukaemia (known as the 'Philadelphia' translocation':"), are associated with particular cancer types..
All cancers are thought to share a common pathogenesis. Each is the outcome of a process of cancer development is based on two constituent processes, the continuous acquisition of heritable genetic variation in individual cells by more-or-less random mutation and natural selection acting on the resultant phenotypic diversity. The selection may weed out cells that have acquired deleterious mutations or it may foster cells carrying alterations that confer the capability to proliferate and survive more effectively than their neighbours. Occasionally, however, a single cell acquires a set of sufficiently advantageous mutations that allows it to proliferate autonomously, invade tissues and metastasize.
The DNA sequence of a cancer cell genome, and indeed of most normal cell genomes, has acquired a set of differences from its original fertilized egg. These are called somatic mutations-to distinguish them from germline mutations that are inherited from parents and transmitted to offspring.
The somatic mutations in a cancer cell genome may encompass several distinct classes of DNA sequence change. These include substitutions of one base by another; insertions or deletions of small or large segments of DNA; re arrangements, in which DNA has been broken and then rejoined to a DNA segment from elsewhere in the genome; copy number increases from the two copies present in the normal diploid genome, sometimes to several hundred copies (known as gene amplification); and copy number reductions that may result in complete absence of a DNA sequence from the cancer genome
The cancer cell may have acquired, from exogenous sources, completely new DNA sequences, notably those of viruses such as human papilloma virus, Epstein Ban virus, hepatitis B virus, human T lymphotropic virus 1 and human herpes virus 8, each of which is known to contribute to the genesis of one or more type of cancer,
The cancer genome will also have acquired epigenetic changes which alter chromatin structure and gene expression, and which manifest at DNA sequence level by changes in the methylation status of some cytosine residues..
The thousands of mitochondria present in cells each carry a circular genome of approximately 17 kilobases. Somatic mutations in mitochondrial genomes have been reported in many human cancers, although their role in the development of the disease is not clear.
The mutations found in a cancer cell genome have accumulated over the lifetime of the cancer patient. It is likely that the mutation rates of each of the various structural classes of somatic mutation differ and that there are differences among cell types too. Mutation rates increase in the presence of substantial exogenous mutagenic exposures, for example tobacco smoke carcinogens, naturally occurring chemicals such as aflatoxins, which are produced by fungi, or various forms of radiation including ultraviolet light. These exposures are associated with increased rates of lung, liver and skin cancer, respectively,
The rest of the somatic mutations in a cancer cell genome have been acquired during the segment of the cell lineage in which predecessors of the cancer cell already show phenotypic evidence of neoplastic change For example, colorectal and endometrial cancers with defective DNA mismatch repair due to abnormalities in genes such as MLHl and MSH2, show increased rates of acquisition of single nucleotide changes and small insertions/deletions at polynucleotide tracts.
Each somatic mutation in a cancer cell genome, whatever its structural nature, may be classified according to its consequences for cancer development. Driver' mutations confer growth advantage on the cells carrying them and have been positively selected during the evolution of the cancer. They reside, by definition, in the subset of genes known as 'cancer genes'. The remainder of mutations are 'passengers' that do not confer growth advantage, but happened to be present in an ancestor of the cancer cell when it acquired one of its drivers.
A driver mutation is causally implicated in oncogenesis and gives growth advantage to the cancer cell and has been positively selected in the microenvironment of the tissue in which the cancer arises. A driver mutation need not be required for maintenance of the final cancer (although it often is) but it must have been selected at some point along the lineage of cancer development shown in Fig. 1.
A passenger mutation has not been selected, has not conferred clonal growth advantage and has therefore not contributed to cancer development.

The known cancer genes are wide in their tissue specificities and mutation prevalences. Some, for example TP53 and KRAS, are frequently mutated in diverse types of cancer whereas others are rare and/or restricted to one cancer type. In some cancer types, for example colorectal and pancreatic cancer, abnormalities in several known cancer genes are common. In contrast, in gastric cancer, relatively few mutations in known cancer genes have been reported.
Approximately 90% of the known somatically mutated cancer genes are dominantly acting, that is, mutation of just one allele is sufficient to contribute to cancer development.

For some cancers, classification and treatment protocols are now defined by the presence of abnormal cancer genes.eg acute myeloid leukaemia, for example, is subclassified on the basis of the presence of abnormalities involving specific cancer genes. Each subtype has a characteristic gene expression profile, cellular morphology, clinical syndrome, prognosis and opportunity for targeted therapy.

Stratton et al 2009 The cancer genome A review. Nature vol 458 pp 719-724

Diet restriction and cancer development

It is well established that dietary restriction, which involves limiting nutrient intake below normal levels but without reaching malnutrition, extends lifespan, youthfulness, age-associated traits and diseases, including cognitive deterioration and cancer in most, if not all, species - probably including humans, This might be due to the evolutionary advantage of keeping alive under suboptimal nutrient availability, and postponing reproduction until food is plentiful.

But dietary restriction does not affect all types of cancer similarly, raising questions about the generality of its effects and its mode of action in cancer. 'Writing in Nature 9th April 2009 , Kalaany and Sabatini and with a commentary by Brunet describe the behaviour of address these questions in both human tumour cells and animal models of human cancer.
When human-tumour cell lines are implanted into mice, some lines cannot expand if the animals' caloric intake is reduced by 40% for a period of 3 weeks. The cell lines that were resistant to the antitumour benefits of this nutrient restriction carried mutations that led to the constitutive (continuous) activation of the signalling pathway mediated by the hormone insulin. These cell lines had mutations that activated the enzyme PI3K, a key component of the insulin signalling pathway, or inactivated PTEN phosphatase, an enzyme that counteracts PI3K action. So it seems that, to exert its anticancer benefits, limited dietary intake must reduce insulin-mediated signalling.
In further experiments, only tumours with an active PI3K pathway were resistant to dietary restriction. What's more, activating this pathway was both necessary and sufficient for tumour resistance to reduced food intake. Finally, the FOXO proteins, which are major down stream targets of the PI3K signalling and affect gene transcription , seems to execute the effects pof dietary restriction as FOXO transcription factors were inactivated in the tumours resistant to reduced nutrient intake.
There was an increase in programmed cell death (apoptosis). Reduced food intake could affect other cellular processes that contribute to tumour size, cell proliferation; or trigger autophagy, a 'self-eating' cellular process that would help to recycle nutrients and ward off cancer by eliminating damaged proteins or organelles; or it might help to reduce the growth of new blood vessels in tumours - a process known as angiogenesis - thus affecting the tumour micro environment rather than the tumour cells.
Dietary restriction in moderation might reduce the chances of developing cancer along with not smoking.
Brunet 2009 When restriction is good . Nature vol 458 pp 713-4
Kalaany and Sabatini 2009 Tumours with P12K activation are resistant to dietary restriction. Nature vol 458 pp 725 - 731

severe malnutrition defininition WHO

On May 22, WHO and UNICEF change the definition of new case severe acute malnutrition based on the 2006 WHO growth standards.' Before the global food crisis, a 2006 review estimated that 13 million children had such malnutrition.' By January, 2009, aid agencies reported about 19 million affected. Calls were made for the disease-burden demand to be met with increased supply of treatment services.
Numbers of children diagnosed as malnourished vary greatly depending on which case definition is used. Each has advantages and disadvantages, and is useful for particular purposes. Malnutrition for admission to feeding programmes was originally defined by low weiqht-for-aqe. This definition was changed to weiqht-for-heiqht to better identify children who would benefit most from treatment. Weight-for height expressed as Z scores is useful for surveys, yet many treatment programmes admit children with conceptually simpler %-of-median measures. (Minus 1 Z score=l standard deviation below a normally distributed population median. Nutritional oedema is also part of the case definition for severe acute malnutrition.) More recently, focus has been on mid-upper-arm circumference.'
WHO growth standards are an international gold standard describing how children should grow when measured by weight and height. Previously, severe acute malnutrition was defined as weight-for-height <70% or ←3 Z scores below the National Centre for Health Statistics (NCHS) median. The new case definition is weight-for-height ←3 Z scores below the WHO growth standards median. The diagnostic threshold of mid-upper-arm circumference has also been changed from 110 mm to 115 mm.
Increases in the diagnoses of severe acute malnutrition with the new WHO weight-for-height criteria have been noted. As different countries use different case definition it is difficult to know the true extent of severe acute malnutrition.
Most countries currently use %-of-median. Changing from <70 % median to ←3Z scores results in dramatic increases in the prevalence of severe malnutrition

Kerac et al 2009 New WHO growth standards: roll-out needs more resources. Lancet vol 374 pp 100-101

El Nino 2009

The Times of July 13th 2009 describes how El Nino, the warming of the Pacific Ocean that creates chaos in global weather patterns, is on its way back, threatening droughts, floods, crop failure and social unrest.
Scientists at America's National Oceanic and Atmospheric Administration (NOAA), warn that a new bout of El Nino is under way as the surface of tropical waters across the eastern Pacific has warmed roughly IC (l.8F) above normal and is still rising. Further down, some 150 meters (500ft) below the surface, the waters are heating up - by around 4C (7.2F).
The persistently warm sea temperatures are important indicators of an El Nino.
There is also a link between the ocean and the atmosphere, with Indonesia tending to dry out as tropical rainfall shifts towards the international dateline in mid-Pacific."
The implications are severe, not just for climate but for the effects on food, water supplies and other commodities. Australia, still recovering from its worst drought in a century will be affected
again if the rains fail with consequences for the wheat belt. Indonesia is one of the world's biggest producers of palm oil - a basic source of income for many of its poor - and a drought would hit this commodity hard. Farming in India is already suffering from an abnormal monsoon, which scientists think could be related to the emerging El Nino. The rains arrived early but stalled. Shortages and food prices caused riots all over the world in 2008, from western Africa to Mexico, Uzbekistan, Haiti and Egypt, as well as consumer protests in Europe and panic in food importing countries. Rice-producing nations were urged to stop hoarding supplies as stocks fell to their lowest levels for 30 years.
The emerging El Nino is expected to continue strengthening over the next few months and reach a peak during the northern hemisphere's winter.

The regions affected
1 Pacific coast of South America prone to floods
2 Australia. Indonesia. Philippines suffer droughts
3 United States tends to have fewer hurricanes. California stormy. and milder winters 4 Southern Africa can suffer drought
5 Parts of East Africa flooded
6 Indian monsoon can be disrupted

El Ninos recur every few years and vary hugely in strength . A severe one badly influences weather patterns across the Pacific and beyond, leading to drought in some areas and heavy rains in others, such as the western coast of South America,
In the last severe episode in 1997-98 torrential rains pulverised California, heat waves swept across Australia and Brazil, forest fires swept Indonesia, eastern Africa was flooded while southern Africa withered under drought, and floods and storms caused billions of dollars' damage to crops and buildings.
There is even a positive aspect for Australians: a recent study has linked El Nino to increased chance of an Australia-in-Australia Cricket Ashes victory. Records from 1882 to 2007 show that the tendency for dry wickets in El Nino years favours their fast bowlers.
This was written by Paul Simons, the Times Weather Correspondent and author of Weird Weather, The Strangest Weather in the World

Effect of weight loss on health

The Nutrition Research Review of 2009 contains an interesting review and meta-analysis of the effect of weight loss on all-cause mortality risk

Overweight and obesity are associated with increased morbidity and mortality, although the range of body weights that is optimal for health is controversial. It is less clear whether weight loss benefits longevity and hence whether weight reduction is justified as a prime goal for all individuals who are overweight (normally defined as BM! > 25 kg/m2).
The review examines the evidence base for recommending weight loss by diet and lifestyle change as a means of prolonging life. An electronic search identified twenty-six eligible prospective studies that monitored subsequent mortality risk following weight loss by lifestyle change, published up to 2008.
The Data were analysed by meta-analysis, giving particular attention to the influence of confounders. Moderator variables such as reason for weight loss (intentional, unintentional), baseline health status (healthy, unhealthy), baseline BM! (normal, overweight, obese), method used to estimate weight loss (measured weight loss, reported weight loss) and whether models adjusted for physical activity (adjusted data, unadjusted data) were used to classify subgroups for separate analysis.
Intentional weight loss per se had no positive effect on all-cause mortality (relative risk (RR) 1·01; P = 0·89), while weight loss which was unintentional or ill-defined was associated with excess risk of 22 to 39 %. Intentional weight loss had a small benefit for individuals classified as unhealthy (with obesity-related risk factors) (RR 0·87 (95 % Cl 0·77, 0·99); P = 0·028), especially unhealthy obese (RR 0·84 (V5 % Cl 0·73, 0·97); P = 0·018), but appeared to be associated with slightly increased mortality for healthy individuals (RR 1·11 (95 % Cl 1·00, 1·22); P = 0·05), and for those who were overweight but not obese (RR 1·09 (95 % Cl 1·02, 1·17); P = 0·008).
There was no evidence for weight loss conferring either benefit or risk among healthy obese. In conclusion, the available evidence does not support solely advising overweight or obese individuals who are otherwise healthy to lose weight as a means of prolonging life. Other aspects of a healthy lifestyle, especially exercise and dietary quality, should be considered. However, well-designed intervention studies are needed clearly to disentangle the influence of physical activity, diet strategy and body composition, in order to define appropriate advice to those populations that might be expected to benefit.
Harrington et al A review and meta-analysis of the effect of weight loss on all-cause mortality risk

Irritable Bowel Syndrome treatment

An Evidence-Based Position Statement on the
Management of Irritable Bowel Syndrome by an
American College of Gastroenterology IBS Task Force

Irritable bowel syndrome (IBS) is a common disorder
characterized by abdominal pain and altered bowel habit
for at least 3 months. With this publication, an American
College of Gastroenterology Task Force updates the
2002 Monograph on IBS in light of new data. A series
of systematic reviews were performed to evaluate the
diagnostic yield of investigations and the efficacy of
treatments for IBS. The Task Force recommends that
further investigations are unnecessary in young patients
without alarm features with the exception of celiac sprue
serology, which may be of benefit in some patients. Further
investigation such as colonoscopy is recommended in those
over 50 years of age and in patients with alarm features.
Trials suggest psyllium fiber, certain antispasmodics, and
peppermint oil are effective in IBS patients although the
quality of the evidence is poor. Evidence suggests that
some probiotics may be effective in reducing overall IBS
symptoms but more data are needed. Antidiarrheals
reduce the frequency of stools but do not affect the overall
symptoms of IBS. 5HT3 antagonists are efficacious in
IBS patients with diarrhea and the quality of evidence is
good. Patients need to be carefully selected, however,
because of the risk of ischemic colitis. 5HT3 agonists are
modestly effective in IBS patients with constipation and
the quality of evidence is good although the possible risk of
cardiovascular events associated with these agents may limit
their utility. Tricyclic antidepressants and selective serotonin
reuptake inhibitors have been shown to be effective in IBS
patients of all subtypes. The trials generally are of good
quality but the limited number of patients included in
trials implies that further evidence could change the
confidence in the estimate of effect and therefore the
quality of evidence was graded as moderate. Nonabsorbable
antibiotics are effective particularly in diarrhea-predominant
IBS and selective C-2 chloride channel activators are
efficacious in constipation-predominant IBS with a moderate
quality of evidence. Psychological therapies may also provide
benefit to IBS patients although the quality of evidence is
poor.

American College of Gastroenterology IBS Task Force 2009 An Evidence-Based Position Statement on the Management of Irritable Bowel Syndrome
Am J Gastroenterology vol 104: S1 – S35;

polyphenols and bone health

This is a very interesting and relevant review by Trzeciakiewicz et in Nutrition Research Review of recent research, which has given insights into dietary components that may optimise bone health and stimulate bone formation.
The vertebrate skeleton is composed of two specialised tissues, cartilage and bone. Bone is essential as its main role is to provide structural support for the body, protect the organs, contribute to haematopoiesis and store minerals. Three distinctly different cell types can be found within bone: the osteoblasts responsible for the synthesis and mineralisation of bone, the osteoclasts implicated in bone tissue resorption and the osteocytes which are the most abundant cells present in the adult skeleton. The integrity of the skeleton requires a dynamic balance between bone formation and bone resorption . If a dysfunction occurs in these two processes, pathologies, such as osteoporosis, can develop.
Fruit and vegetable intake, as well as grains and other plant-derived food, have been associated with decreased risk of major chronic diseases including osteoporosis.This effect has been partially attributed to the polyphenols found in these foods.
Phytochemicals are a large group of plant-derived nonnutritive chemical compounds divided into several classes: phenolics (polyphenols), carotenoids, alkaloids, sterols, terpenes and fibre. Phytochemicals produced by plants are used to protect themselves but recent research demonstrates that certain molecules may protect humans against some pathologies such as cancer, cardiovascular diseases and osteoporosis.
Polyphenols can be divided into different groups depending on the number of phenol rings they contain and on the structural elements bound to these rings. Polyphenols have been classified as phenolic acids, flavonoids, stilbenes, tannins, coumarins and lignans. Among flavonoids, six subclasses exist and share a common structure of two aromatic rings (A and B) bound together by three carbon atoms that form an oxygenated heterocycle (ring C). These are flavones, flavonols, flavanones, isoflavones, flavanols (catechins and proanthocyanidins) and anthocyanidins'F".

Thus, it has been suggested that these compounds may give benefits to bone health through an action on bone cell metabolism. The review shows how some polyphenols can modulate osteoblast function and suggests which cellular signalling pathways are potentially implicated. As yet, few studies have provided clear evidence that phenolic compounds can act on osteoblasts.
Some polyphenols seem to be able to modulate the expression of transcription factors such as runt-related transcription factor-2 (Runx2) and Osterix, NF-KB and activator protein-l (AP-l).
Polyphenols may act on cellular signalling such as mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP), oestrogen receptor and osteoprotegerin/receptor activator of NF-KB ligand (OPGIRANKL) and thus may affect osteoblast functions.
Trzeciakiewicz, et al 2009 When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols. Nutrition Research Reviews vol 22 68-81

Global warming migration

Global Warming induced migraton.
Migration from the farms has long been a feature of the dry areas of Western Africa. Rural life becomes more difficult and populations move to the cities and urban life.
As Global Warming progresses so people will find farming impossible and will move in search of sustenance and work.
10 % of the population would have to move from their homes with a 1-metre rise in sea level. 1 billion live in dry lands vulnerable to drought. The number of people seeking new places to live may reach between 50 million to 1 billion of the world population of 9 billion by 2050.
When Hurricane Katrina hit New Orleans 1.5 million people left in 14 days. Three times the number who moved in the great Dust Bowl migration of 1930s.
The low lying Maldive Islands will disappear under the sea with consequent loss of habitation for the present population.
These movements will overwhelm the refugee laws and humanitarian agencies. The rich and ecological stable countries will be under pressure from this migration.
The global change will range from disasters as with Hurricane Katrina, drought and wildfires , loss of marginal land to desert, sea rises of possibly 3 meters
Knight 2009 The human tsunami FT Weekend Magazine June 20/21 p 24-31

HIV and weight loss

HIV is a grave problem in sub-Saharan and the basic treatment is antiretroviral therapy. Mortality is high during the first few months of treatment, significantly associated with weight loss i.e. reduced BMI. How can the BMI be increased?
The most commonly used supplement in food aid programmes is corn-soy blended flour, a cheap fortified cereal-legume combination that requires cooking.
The results are disappointing.
A controlled trial using an energy dense ready to use fortified pre-cooked lipid paste made from peanuts that resists bacterial contamination is reported in the BMJ of May 30th 2009. And works, increases BMI and lean body mass but does not change mortality.
Which challenges the underlying concepts and ideas. Is weight loss the entire cause of death? There was no increase in micronutrient content of the supplement above normal recommendations. More is not necessarily better.
The editorial quotes Kleiber’s law, that in the face of competitive functional demands, how specific nutrients are used eg energy and pattern of protein deposition will be determined by the relative availability of all other nutrients. A wise thought.
In the resuscitation of inmates of freed concentration camp inmates in 1944 much had to be learnt about the way in which food was reintroduced.
MacDonald et al 2009 Supplementary feeding with either ready o use fortified spread or corn soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised , investigator blinded controlled trail BMJ vol 338 pp 1309-1312
Rollins in Editorial Food supplements and HIVBMJ vol 338 pages 1282-3

Statistics in randomised controlled trials

The use of statistics in randomised controlled trials is central to the whole exercise and it is a terrible waste of everyone’s time when this is neglected. This timely paper in the BMJ id worth the attention of anyone undertaking such trials.
The importance of sample size determination in randomised controlled trials has been widely asserted, and must be reported in published articles. An a priori sample size calculation will determinate the number of participants needed to detect a clinically relevant treatment effect.
The conventional approach is to calculate sample size with four parameters: type I error, power, assumptions in the control group (response rate and standard deviation), and expected treatment effect. Type I error and power are usually fixed at conventional levels (5% for type I error, 80% or 90% for power). Assumptions related to the control group are often prespecified on the basis of previously observed data or published results, and the expected treatment effect is expected to be hypothesised as a clinically meaningful effect. The uncertainty related to the rate of events or the standard deviation in the control group and to treatment effect could lead to lower than intended power.
Charles and his colleagues assessed the quality of reporting sample size calculation in published reports of randomised controlled trials, the accuracy of the calculations, and the accuracy of the a priori assumptions.
In this survey of 215 reports published in 2005 and 2006 in six general medical journals with high impact factors, only about a third (n=73, 34%) adequately described sample size calculations-that is, they reported enough data to recalculate the sample size, the sample size calculation was accurate, and assumptions in the control group differed less than 30% from observed data. This study raises two main issues. The first is the inadequate reporting and the errors in sample size calculations, which are surprising in high quality journals with a peer review process; the second is the large discrepancies between the assumptions and the data in the results, which raises a much more complex problem because investigators often have to calculate a sample size with insufficient data to estimate these assumptions.
Reporting of the sample size calculation has greatly increased in the past decades, from 4% of reports describing a calculation in 1980 to 83% of reports in 2002. This review highlights that some parameters for sample size calculation are frequently absent and that miscalculations occur.
They also found large discrepancies between values for assumed parameters in the control group used for sample size calculations and estimated ones from observed data. Assumed values were fixed at a higher or lower level than corresponding data in the results sections in roughly even proportions, a finding different from the results of a previous study.
These results suggest that researchers, reviewers, and editors do not take reporting of sample size determination seriously. An effort should be made to increase transparency in sample size calculation or, if sample size calculation reporting is of little relevance in randomised controlled trials, perhaps it should be abandoned, as suggested by Bacchetti.

. After years of trials with supposedly inadequate sample sizes, it is time to develop and use new ways of planning sample sizes.

Charles et al 2009 Reporting of samle size calculation in randomised controlled trials: review. BMJ vol 338, pp 1256-1259

Food Waste

The affluent countries waste millions of tons of edible food. Supermarkets, restaurants, canteens and manufactures are identifiable in this respect. For example nearly 500 million pots of yoghurt are thrown away every year in Britain. 50% of food disappears between the plough and the plate. Up to a third of school meals are thrown away, A quarter of food products purchased are thrown away. The Cooperative Supermarket wastes the least food of the British Supermarkets, followed by Morrisons, Tesco, Asda , Waitrose and the worst is Sainsbury’s with over 50 % more waste than the Cooperative Supermarket.
Poor and misunderstood labelling can lead to good food being thrown away.
Obviously food poisoning is a real problem But one can be ultra cautious.
EU food-labelling law require most pre-packed food to carry a “use-by” or “best-before” date, the “best-before” date is a mark of quality, “use-by” date of food safety. But the date may mean that the food could be past its prime but safe to eat. Sell by is for the convenience of the shop and does not reflect any nutritional. Value. All very confusing.
A ridiculous example is bottled water which has been in the ground for thousands of years , but once in a bottle has a brief use by label.

Tristam Stuart No appetite for waste Financial Times Weekend Magazine July 4/5 2009. p 30-35
Based on an important book
Waste: uncovering the Global Food Crisis Author Tristram Stuart : Penguin Publication.

Garlic

This is a very interesting paper in Critical Reviews in Food Science and Nutrition 2009 on the merit of garlic in the diet.
Natural plant products have a real place in combating various physiological threats including oxidative stress, cardiovascular problems, cancer, and immune dysfunction.
Garlic (Allium sativum} holds a unique position in history and was recognized for its therapeutic potential. Recent advancements in the field of immunonutrition, physiology, and pharmacology have emphasised its importance as a functional food against various pathologies. Extensive research work has been. carried out on the health promoting properties of garlic, often referred to its sulfur containing metabolites i.e. allicin and its derivatives.
Alicin
Diallyl sulfide, Diallyl disulfide Diallyl trisulfide AllylMethyl sulfide AllylMethyl disulfide Allylmethyl trisulfide 2-vinyl-4H-I,3-dithiin
3-vinyl-4H-l,2-dithiin
E- Ajoene , Z-Ajoene


S-allyl-Lcysteines
S-allylmercaptocysteine


Garlic has many modes of preparation which are believed to be effective against health risks and even used as dietary supplements such as age garlic extract (AGE) and garlic oil etc. Its components/formulations can scavenge free radicals and protect membranes from damage and maintains cell integrity. It also provides cardiovascular protection by lowering of cholesterol, blood pressure, anti-platelet activities, and thromboxane formation thus providing protection against atherosclerosis and associated disorders. Besides this, it possesses antimutagenic and antiproliferative properties that are interesting in chemoprevenrive interventions. Several mechanisms have been reviewed in this context like activation of detoxification phase-I and II enzymes, reactive oxygen species (ROS) generation, and reducing DNA damage etc. Garlic could be useful in preventing the suppression of immune response associated with increased risk of malignancy as it stimulates the proliferation of lymphocytes, macrophage phagocytosis, stimulates the release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma, and enhances natural killer cells.
Masood Sadiq Butt et al 2009 Garlic : Nature’s protection against physiological threats, Critcal Reviews in Food Science and Nutrition vol 49, pp 538-5551

plant hormones

Recent advances and emerging trends in plant hormone signalling
Aaron Santner ' & Mark Estelle have reviewed plant homones in Nature 25th June 2009

In eating frit and vegetables there are many different molecules whose function when eaten by man is unknown included in these are plant hormones.
Plant growth and development is regulated by plant hormones. During the last 15 years the number of known plant hormones has grown from five to at least ten. Furthermore, many of the proteins involved in plant hormone signalling pathways have been identified, including receptors for many of the major hormones. Strikingly, the ubiquitin-proteasome pathway plays a central part in most hormone-signalling pathways. In addition, recent studies confirm that hormone signalling is integrated at several levels during plant growth and development.


Because plants have a sessile lifestyle, they must adjust to numerous external stimuli and coordinate their growth and development accordingly. The plant hormones, a group of structurally unrelated small molecules, are central to the ntegration of diverse environmental cues with a plant's genetic program. The 'classical' phytohormones, identified during the first half of the twentieth century, are auxin, abscisic acid, cytokinin, gibberellin and ethylene.
More recently, several additional compounds have been recognized as hormones, including brassinosteroids, jasrnonate, salicylic acid, nitric oxide and strigolactcnes

Plants also use several peptide hormones to regulate various growth responses, Most hormones are involved in many different processes ( hormone synthesis, transport and signalling pathways, as well as by the diversity of interactions among hormones) to control growth responses. throughout plant growth and development. Genetic screens have identified many of the proteins involved in hormone signalling
Receptors for auxin, gibberellin , jasmonate and abscisic acid have now been identified. . Some hormones (cytokinins, ethylene and the brassinosteroids) use well-characterized signalling mechanisms.
The auxin and jasmonate receptors, as well as proteins in gibberellin signalling, have highlighted a novel mechanism for hormone perception in which the ubiquitin--proteasome pathway.
Has this any relevance to human nutrition? Who knows , but we do know that eating fruit and vegetables is good for health, and these plant hormones may be of biological value.
Santner and Estelle 2009 Recent advances and emerging trends in plant hormone signalling. Nature vol 459 pp 1071-78

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trans fats in the diet

A review of trans fats by D Mozaffarian, A Aro and W C Willett indicating that these ar not too good for out health.
Growing evidence indicates that trans-fatty acids (TFA) adversely affect cardiovascular health. As part of the World Health Organization (WHO) Scientific Update on TFA, we reviewed the evidence for effects of TFA consumption on coronary heart disease (CHD).
The effects of TFA consumption on risk factors most consistently seen in both controlled trials and observational studies included adverse lipid effects (for example low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), total/HDL-C ratio), proinflammatory effects (for example tumor necrosis factor- activity, interleukin-6, C-reactive protein) and endothelial dysfunction. These effects were most prominent in comparison with cis unsaturated fats; adverse effects on total/HDL-C and endothelial function were also seen in comparison with saturated fatty acids (SFA). TFA may also worsen insulin sensitivity, particularly among individuals predisposed to insulin resistance; possible effects on weight gain and diabetes incidence require further confirmation. Five retrospective case–control studies and four prospective cohort studies demonstrated positive associations between TFA consumption and CHD events. A meta-analysis of prospective studies indicated 24, 20, 27 and 32% higher risk of myocardial infarction (MI) or CHD death for every 2% energy of TFA consumption isocalorically replacing carbohydrate, SFA, cis monounsaturated fatty acids and cis polyunsaturated fatty acids, respectively. The differential effects of specific TFA isomers may be important but are less well established. The available evidence indicates that trans-18:1 and particularly trans-18:2 isomers have stronger CHD effects than trans-16:1 isomers. The limited data suggest that the experimental effects of ruminant and industrial TFA are similar when consumed in similar quantities, but very few persons consume such high levels of ruminant TFA, and observational studies do not support adverse CHD effects of ruminant TFA in amounts actually consumed.
Conclusions:
Controlled trials and observational studies provide concordant evidence that consumption of TFA from partially hydrogenated oils adversely affects multiple cardiovascular risk factors and contributes significantly to increased risk of CHD events. The public health implications of ruminant TFA consumption appear much more limited. The effects of specific TFA isomers require further investigation.
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D Mozaffarian, A Aro and W C Willett (2009)Health effects of trans-fatty acids: experimental and observational evidence European Journal of Clinical Nutrition 63, S5–S21;

obesity epidemiology

The vol 87 (2009) of the Millbank Quarterly contains a big review on obesity. Sallis and Glanz ( vol 87 pp 123-154) have written a timely reminder that where there is little provision for exercise then obesity is more prevalent. : Numerous cross-sectional studies have consistently demonstrated that some attributes of built and food environments are associated with physical activity, healthful eating, and obesity. Residents of walkable neighborhoods who have good access to recreation facilities are more likely to be physically active and less likely to be overweight or obese. Residents of communities with ready access to healthy foods also tend to have more healthful diets. Environmental, policy, and societal changes are important contributors
to the rapid rise in obesity over the past few decades, and there has been substantial progress toward identifying environmental and policy factors related to eating and physical activity that can point toward solutions

ageing and vitamin D

This is a good review by Oudshoorn et al on the important subject of vitamin D in the elderly.
Vitamin D is a pleiotropic hormone. Besides the effects on classical tissues like bone and intestine, vitamin D has an effect on many more tissues. Effects of vitamin D metabolites can occur via endocrine, paracrine or autocrine mechanisms.
Ageing increases the risk of vitamin D deficiency and is associated with vitamin D resistance and less efficient intestinal Ca absorption and renal reabsorption. Vitamin D supplementation doses needed to treat vitamin D deficiency and secondary hyperparathyroidism vary considerably between individuals. This makes it necessary for clinicians to give tailored advice to patients when treating hypovitaminosis D, taking into account these age-related effects and other characteristics that influence vitamin D status and Ca homeostasis.
In general, mobile, Caucasian community-dwelling elderly, who have a varied diet, need vitamin D supplementation of 10-20 μg (400 IU – 800 IU ) /d to reach serum vitamin D levels of 50-75 nmol/l. Frail or institutionalised elderly on the other hand are suggested to need up to 50 ug (2000 IU)/). The effectiveness of this high-dose vitamin D supplementation in raising serum 250HD3 levels adequately has been demonstrated in several clinical trials. However, good evidence for the optimal dose of vitamin D supplementation in specific high-risk groups is still lacking.
Oral supplementation is the most effective intervention to treat vitamin D deficiency. Ergocalciferol is equally as effective as cholecalciferol in raising serum 250HD3 levels. Daily dosing is the most efficient interval to raise serum 250HD3 concentrations when compared with weekly or monthly administration.
Although vitamin D supplementation therapy is generally regarded as safe, cases of iatrogenic and accidental overdose with cholecalciferol have been reported. . Most safety data concerning the use of high-dose cholecalciferol supplementation come from observations in relatively young individuals. Few studies have used high-dose cholecalciferol supplementation for longer periods in frail, older patients. Frail old people, particularly the institutionalised, often have poor daily fluid intake, use diuretics and have less thirst sensation than younger persons.
All clinicians who frequently treat older patients should take a proactive approach to screening at-risk individuals for vitamin D deficiency, as this condition is still very prevalent. When treating patients for vitamin D deficiency, Ca intake should be assessed. Possible unwanted effects of long-term vitamin D supplementation and the effects of hypervitaminosis D should be studied in forthcoming trials.
Oudshoorn et al Ageing and vitamin D deficiency : effects on calcium homeostasis and consideration or vitamin D supplementation .

minerals and vitamins in bone health

This is a very good review of such an important topic. Very thoughtful
Nutrition is important to bone health, and a number of minerals and vitamins have been identified as playing a potential role in the prevention of bone diseases, particularly osteoporosis. Despite this, there is currently no consensus on maximum levels to allow in food or as dietary supplements. The benefits of supplementation of populations at risk of osteoporosis with Calcium and vitamin D are well established. Prolonged supplementation of Ca and vitamin D in elderly bas been shown to prevent bone loss, and in some intervention studies to prevent fragility fractures.
Calcium intakes and recommendations vary form country to country but range between 700 mg/d to 1200 mg depending on age and gender.
Vitamin D 1000 IU ( 25 μg/d ) has been recommended but not yet achieved.

Although Phosphorous is essential to bone health, the average intake is considered to be more than sufficient and supplementation could raise intake to adverse levels. The role of vitamin K in bone health is less well defined, though it may enhance the actions of Calcium and vitamin D. Strontium administered in pharmacological doses as the ranelate salt was shown to prevent fragility fractures in postmenopausal osteoporosis. However, there is no hard evidence that supplementation with Strontium salts would be beneficial in the general population. Magnesium is a nutrient implicated in bone quality, but the benefit of supplementation with foodstuffs remains to be established. A consensus on dietary supplementation for bone health should balance the risks, for example, exposure of vulnerable populations to values close to maximal tolerated doses, against evidence for benefits from randomised clinical trials, such as those for Ca and vitamin D. Feedback from community studies should direct further investigations and help formulate a consensus on dietary supplementation for bone health.
Bonjour J-P et al 2009 Minerals and vitamins in bone health : the potential value of dietary enhancement. Brit J Nutrition vol 101 pp 1581-1596