Vitamins and the prevention of diseases.

Faith in vitamin E, β carotene, and oestrogen endures despite the evidence

Throughout the 1990s there was a widespread believe that vitamin E could help prevent cardiovascular disease. Large observational studies found clear evidence of benefit. Since then. equally large and more convincing randomised trials have found the opposite.
Belief in the protective properties of vitamin E persists. In scientific articles citing the early observational studies, some half were still arguing in favour of vitamin E as late as 2003 despite there being a landmark trial five years earlier overturning the observational studies findings..
Belief in the anti-cancer potential of β carotene has also persisted. The notion that β carotene prevents cancer was discredited by randomised trials published in 1996. In another citation analysis, two thirds of citations to the original observational work were still favourable 10 years later. Most of the articles simply ignored the later evidence. Results were similar for the more recently discredited idea that oestrogen protects post-menopausal women against dementia.
In the vitamin E analysis, articles in specialist journals were more likely than articles in general journals to defend the protective properties of vitamin E. So were articles that reported their own observational data, those from outside the US. and those that failed to cite the key (negative) randomised trial.
BMJ 2007, Faith in vitamin E, β carotene, and oestrogen endures despite the evidence . vol 335 p 1234
Quoting a review in JAMA 2007;298:2517-26
It is interesting that vitamins may in an epidemiological study be shown to protect against all manner of diseases. But vitamins may be a marker of other nutritional constituents.
One area where there is a better basis for believing that there is protective role for a vitamin is the use of folic acid to reduce the incidence of neural tube disorders. The UK Food Standards Agency has recommended the fortification of flour with folic acid. Here there is a clear evidence of efficacy. Never the less there is continued dissent because of a misinterpretation of trial data. The suggestion is that folic acid fortification increases the incidence of colonic polyps The results do not show this.
The real problem is that vitamins are present in food in minute amounts and act in minute amounts.
What is being asked is that they also have a pharmacological action ie at an increased dosage.
Such claims have to be judged by the same criteria as a pharmacological agent . Backed by Clinical trials. The financial reward to Drug Firms would be so small as to rule out such trials
Clearly this is the province of Research Councils.
Bayston et al 2007, Folic acid fortification and cancer risk The Lancet vol 370, p 2004

Technorati Profile

phytosterol enriched margarines and effectiveness on blood lipids

Phytosterol-stanol enriched margarines are an attractive method to reduce the blood lipids.
In an extensive study in Holland groups of individuals using either cholesterol lowering drugs or phytosterol-stanol enriched margarines ,or both cholesterol lowering drugs and phytosterol-stanol enriched margarines and a control group were looked at over a 5 year period.
The reduction in lipid concentrations on average was
Cholesterol lowering drugs - -17%
Phytosterol stanol enriched margarine - -4%
cholesterol lowering drugs, plus phytosterol-stanol enriched margarines -29%
control 0%
The conclusion was that on their own the phytosterol-stanol enriched margarines were of modest value but with cholesterol reducing drugs had an enhancing effect.
Jong et al 2007 Exposure and effectiveness of phytosterol/stanol-enriched margarines
Vol 61, 1407-1415

Vegetarians and bone fractures

A diet that is outside the accepted norm may raise concerns for its adequacy in terms of nutrients and whether or not this diet has inbuilt deficiencies
The vegetarian diet is one such concern. . The Oxford cohort of the European Prospective Investigation into Cancer and Nutrition ( EPIC-Oxford ) conducted a survey of vegetarians and non vegetarians in Oxford for bone fracture.
They studied vegetarians, vegans, meat eaters and fish eaters for self reported bone fractures. Spontaneous bone fractures are a rough and ready estimate of bone fragility eg osteoporosis.
The conclusion is that there is no difference in fracture rate between vegetarians, meat eaters and fish eaters but is very slightly greater for vegan.
At the end of the day the conclusion was that the differences was that calcium intake rather than the prime strategy of the diet mattered.
Appleby et al (2007) Comparative fracture risk in vegetarians and non-vegetarians in EPIC-Oxford. European Journal of Clinical Nutrition vol 62, 1400-1406

Variations in boy girl baby ratios.

In Nature 2007, vol 450 p 765 there is a fascinating summary of two papers describing variations in male female ratios in babies
. Biol. Lett. doi:10.1O98/rsbl.2007.0482 (2007);
Proc. R. Soc. B doi:10.1098/rspb.2007.1401 (2007)
Evolutionary theory suggests that sexual creatures increase the number of descendants if they have more sons than daughters when conditions are optimal and more daughters than sons in less ideal circumstances. How this happens is not clear.
It may also be that after wars, more male babies are born than female.
Samuli Helle, of the University of Turku in Finland, and his colleagues report a correlation between the annual mean temperature in northern Finland and the sex ratio of newborns in three populations of indigenous Sami people for the years 1745-1890. The team compared demographic data from the parish registers of Lutheran churches with a climatic record reconstructed from tree rings and an index of the North Atlantic Oscillation. Warmer years brought an increased proportion of boys, in keeping with theory.
Elissa Cameron, of the University of Pretoria in South Africa, and her colleagues raised the proportion of daughters in mouse litters by lowering the blood glucose levels of females during conception. The researchers added dexamethasone, a steroid that blocks glucose uptake into the blood, to the drinking water of female mice for three days while the animals had access to a mate. Only 41,9% of the litters of dexamethasone-treated mice were male, compared with 53.5% in control litters.
This suggests a fascinating research project. The effect of diet on the male female ratio of offspring. Easy in mice. Firstly a nutritionally adequate , an adequate and insufficient diet.
Pregnancy can often happen if the girl is drunk so study alcohol ( beer, white and re wine )
Then the vast array of food and herb aphrodisiacs, which include oysters and chocolate.

enzyme kinetics and protein configuration

When I first studied Biochemistry in RB Fisher in Edinburgh in the early 1960s I was draw into his enthusiasm for enzyme kinetics. I was so ignorant and yet had a medical degree and was entranced by this topic. He was very mathematical in his approach.
I wondered at the time if there was but one chemical structure for a protein enzyme. and that different biochemical processes used different sections of the structure. I was so obviously wrong. This was before the expansion of knowledge of structure and structure relationships that we now enjoy.
In Henzler-Wildman et al Nature 2007 Intrinsic motions along an enzymatic reaction trajectory vol 450 pp 838-44 there is a fascinating paper which uses a variety of analytical techniques to identify how a protein assumes a shape which maximises and facilitates enzyme function.
A folded protein is not a unique structure, but includes an ensemble of folded states at physiological temperatures.
Protein folding does not happen by random sampling of all possible conformation. The rearrangements within a folded protein are directed by the energy requirements. Although the lowest energy structures can often be determined experimentally, an understanding of other conformations and the transitions among them is still in its infancy.
A relationship between structure and freedom of movement and shape plasticity results in the unique power of biocatalysts (enzymes). The chemical mechanisms of many enzymatic reactions are known in great detail thanks to advances in classical enzymology and structural biology. For a number of enzymes, snapshots of conformations that are sampled during catalysis have been obtained using ligands, substrates and inhibitors. Recently, transitions between these states have been measured by nuclear magnetic resonance (NMR) relaxation experiments with substrate analogues or during catalysis, as well as by single-molecule fluorescence resonance energy transfer (FRET). In this paper the authors explore how an enzyme, adenylate kinase, reaches a catalytically competent conformation in which the reactive groups are brought into close proximity in a position favouring catalysis.
Using X-ray crystallography, NMR, single-molecule FRET, normal mode analysis (NMA) and molecular dynamics simulations, they identify1 conformational substates during a reaction.
The motions in the form of the protein enzyme are as one might anticipate, not random but follow a pathway which enables a configuration capable of effective catalytic activity.

Grip strength , metabolic syndrome

Sarcopenia that is the loss of muscle mass and strength with age, and is also a feature of type 2 diabetes in the older person .
In diabetes there is a relationship between increased glucose concentration and weaker muscle strength.
In the Hertfordshire cohort study impaired grip strength runs in parallel with the features of the metabolic syndrome.
The paper suggests that there may be place for the use of the grip test in the clinic.
Sayer et al 2007 Grip strength and the metabolic syndrome: findings from the Hertfordshire Cohort study Q.J.Med vol 100, 707-713

Grip strength of value in the metabolic syndrome

Sarcopenia that is the loss of muscle mass and strength with age, and is also a feature of type 2 diabetes in the older person .
In diabetes there is a relationship between increased glucose concentration and weaker muscle strength.
In the Hertfordshire cohort study impaired grip strength runs in parallel with the features of the metabolic syndrome.
The paper suggests that there may be place for the use of the grip test in the clinic.
Sayer et al 2007 Grip strength and the metabolic syndrome: findings from the Hertfordshire Cohort study Q.J.Med vol 100, 707-713

mianserin, energy restriction and life span

In a remarkable study , 88, 000 chemicals were tested to see if they could extend the life span of the worm ( caenorhabditis elegans) . This worm may normally live for up to 3 weeks. Of all the drugs tested only the anti-depressant mianserin significantly extended the worms life span by almost a third.
Mianserin is a blocker of the neural signalling by the neurotransmitter serotonin.
Further studies on the mechanism show analogies with nutritional deprivation which in appropriate circumstances may also extend life span.
Petrascheck et al 2007 An antidepressant that extends lifespan in adult caenorhabditis elegans Nature vol 450, pp 553-7

Protein movements across cell membranes.

The molecular mechanism of protein translocation, is the subject of a review by Rapoport in Nature.
Proteins transported across the eukaryotic endoplasmic reticulum membrane or the prokaryotic plasma membrane include soluble proteins, such as those ultimately secreted from the cell or localized to the endoplasmic reticulum lumen, and membrane proteins, such as those in the plasma membrane or in other organelles of the secretory pathway.
Soluble proteins cross the membrane completely and usually have amino-terminal, cleavable signal sequences, the major feature of which is a segment of 7-12hydrophobic amino acids.
Membrane proteins have different topologies in the lipid bilayer, with one or more transmembrane segments composed of about 20 hydrophobic amino acids; the hydrophilic regions of these proteins either cross the membrane or remain in the cytosol.
Both types of proteins are handled by the same machinery within the membrane: a protein-conducting channel. The channel allows soluble polypeptides to cross the membrane and hydrophobic transmembrane segments of membrane proteins to exit laterally into the lipid phase.
An important step in the biosynthesis of many proteins is the partial or complete translocation across the endoplasmic reticulum membrane. Most of these proteins are translocated through a protein-conducting channel that is formed by a conserved, heterotrimeric membrane-protein complex, the Sec61 or SecY complex.
Depending on channel binding partners, polypeptides are moved by different mechanisms: the polypeptide chain is transferred directly into the channel by the translating ribosome, a ratcheting mechanism is used by the endoplasmic reticulum chaperone BiP. Structural, genetic and biochemical data show how the channel opens across the membrane, releases hydrophobic segments of membrane proteins laterally into lipid, and maintains the membrane barrier for small molecules.
Rapoport 2007, Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature vol 450, 663-669.

Pharmacotherapy for obesity

The ingenuity that has been devoted to obesity is boundless. Whether this be psychological, surgical or therapeutic .
As weight losses, achieved with lifestyle intervention are modest and limited by high rates of recidivism and compensatory slowing of metabolism there is a potential for even greater use of drug treatment In a meta analysis review by Rucker the use of the long term efficacy of anti-obesity drugs in reducing weight and improving health status is looked at.
The trials (30 trials of one to four years duration) were reviewe, all lasted for over a year. .
The drugs studied were
Orlistat, a gastrointestinal lipase inhibitor
sibutrarnine. a central!) acting monoamine reuptake inhibitor,
rimonabant an endocannabinoid receptor antagonist,
Compared with placebo, orlistat reduced weight by an average of 2.9 kg ,
sibutramine by 4.2 kg
rimonabant by 4.7 kg.
Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss than control subjects.
Ortistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
Sibutramine improved concentrations of high density lipoprotein cholesterol and triglycerides but raised blood pressure and pulse rate.
Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
Rucker et al 2007, Long term pharmacotherapy for obesity and overweight: updated meta-analysis BMvol 335, 1194-9

Physiological p53 function

P53 is regarded as the guardian of the genome, which regulates the cellular response to stress. It is a tumour suppressor gene , but does p53 have a physiological role? It has a function in maternal reproduction. Sufficient LIF ( leukaemia inhibitory factor) a cytokine is required for implantation of the fertilised ovum and the embarkation on a successful pregnancy. This is regulated by p53.
What the role in the male is remains to be seen? Also from LIF’s name there are other functions attributable to LIF which must be the start of an interesting story.
Hu et al 2007, p53 regulates maternal reproduction through LIF. Nature vol 450 pp721-724

The fruit fly, evolution and a potential for nutritional studies.

Many of the classical studies in genetics have used the fruit fly Drosophila. Why the Drosophila?. It has been suggested that the original scientist who used Drosophila was intending to study another insect but as he ate his lunch there was a fruit fly on his banana.
The sequence of the genomes of 12 fly species has now been completed. During evolution, protein coding genes are conserved but show variation. . The vast majority of multigene families are found in all the 12 genomes Drosophila studies. Though there are novel genes peculiar to a particular species.
A major review in Nature looks at the genes involved in genetic selection. And why the different Drosophila species emerge and indeed why they are different. They have examined the traditional protein coding genetics, motifs that regulate gene expression and additional possible mechanisms for the pre-translational processing of mRNAs or alternative modes of translation.
Rapid evolution has occurred in the genes involved in olfaction, immunity and insecticide resistance.
The Drosophila has a simple metabolic system for example the control of glucose and lipid metabolism. Studies in Drosophila metabolic processes have equivalence in mammalian tissue and hence are a good model to study the gene protein metabolic systems. Similarly the control of total size, organ size, cell competition and apoptosis, control of cell division , cell shape and arrangement can be studied in the fruitfly .The feedback systems coordinating various processes are similarly well studied in the fly.
Gunter et al Editor 2007 Genome labour bear fruit. Nature vol 450 pp 183-241

Obesity and cancer incidence

Gillian Reeves and her colleagues have studied whether there is a relationship between body mass index (kg/m1) and cancer incidence and mortality. They studied a large group of 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. They looked at the Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted forage, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy.
45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38,1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50,1.23 to 1.83), multiple myeloma (1.31,1.04 to 1.65), pancreatic cancer (1.24, 1,03 to 1.48), non-Hodgkin's lymphoma (1.17,1.03 to 1,34), ovarian cancer (1.14,1.03 to 1.27), all cancers combined (1,12,1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in prernenopausal women (1.61,1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status.
They concluded that increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese.
They suggest that for endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity
Association with adenocarcinoma of the oesophagus makes sense as acid reflux will be a potent irritant and hence a stimulus for malignant change. The endometrial cancer
Reeves et al 2007 Cancer incidence and mortality in relation to body mass index in the million women study: cohort study. BMJ vol 335 pp 1134-9
Calle 2007 Editorial Obesity and cancer BMJ vol 335, pp 1107-8
Maybe the other side of this story is important. Malignant change is reduced by decreased energy intake. That it is not so much the obesity but the nutritional load and the metabolic stress incurred.

obesity and a choir

It is interesting to make observations on common conditions and groups. When I first came to Edinburgh as a student in 1954 there were groups of elderly people with rickets sitting on the benches alongside a main thorough fare.
Last weekend I went to a Christmas Choir concert here in Fife. There must have been over 50 children mostly girls aged 10-12years singing in a choir. There are many quoted figures for obesity rates but in this group only 2 or at the most 3 who were obese. The remainder were slim children,. This is in contrast to the young people using those aisles in the supermarket which carry biscuits, sweets, drinks, alcoholic or none alcohol where fat people abound. .
Does this mean that singing prevents obesity? Or that the type of child who sings in a choir comes from a social group wee nutrition is important.

Action on additives

The Food Commission magazine, Food Magazine has several good websites
including
Action on Additives www.actiononadditives.com
which lists products and additives.

CO2 uptake by the Ocean

The ocean is very important in modulating atmospheric carbon dioxide through a variety of physical, chemical and biological processes.. A key process responsible for about three-quarters of the surface to deep-ocean gradient in dissolved inorganic carbon (DIC) is the biological carbon pump. This transports carbon bound by photosynthesis from the sunlit surface layer to the deep ocean. Small changes in this pool, for example, caused by biological responses to ocean change, would have a strong affect on atmospheric CO2.
At present, one of the most far-reaching global perturbations of the marine environment is caused by the massive invasion of fossil fuel CO2; into the ocean, making it the second largest sink for man made carbon dioxide after the atmosphere itself. CO2 entering the ocean alters the seawater carbonate equilibrium, decreasing pH and shifting dissolved inorganic carbon away from carbonate towards more bicarbonate and CO2-
The oceans have absorbed nearly half of the fossil-fuel carbon dioxide (CO2) emitted into the atmosphere since pre-industrial times’, causing a measurable reduction in seawater pH and carbonate saturation. If CO2 emissions continue to rise at current rates, upper-ocean pH will decrease to levels lower than have existed for tens of millions of years and, critically, at a rate of change 100 times greater than at any time over this period. Recent studies have shown effects of ocean acidification on a variety of marine life forms, in particular calcifying organisms.
In a paper in Nature Riebesell et al show that the dissolved inorganic carbon consumption of a natural plankton community increases with rising CO2. The community consumed up to 39% more dissolved inorganic carbon at increased CO2 partial pressures compared to present levels, whereas nutrient uptake remained the same.
This excess carbon consumption was associated with higher loss of organic carbon from the upper layer of the stratified mesocosms. If applicable to the natural environment, the observed responses have implications for a variety of marine biological and biogeo-chemical processes, and underscore the importance of biologically driven feedbacks in the ocean to global change.
Riebesell et al 2007 Enhanced biological carbon consumption in a high CO2 ocean Nature vol 450 pp 546-8

Fibonacci number and nutritional hazards

A really interesting programme is the Melvin Bragg programme on the BBC Radio 4.
He and guests talk about all manner of intelligent topics including mathematics
He sends on request a newsletter which summarises his programme.
The Fibonacci sequence is one of those fascinating games which mathematicians indulge in.
It struck me that the breeding rabbits and the numbers are not dissimilar to the number of unfortunate effects food, it is claimed, can have on the unsuspecting public.
These stick in the text books and like the rabbits never die, only accumulate. The public meanwhile lives longer each century and enjoys food. .
Fibonacci introduced the number sequence through the analogy of breeding rabbits. He based his model on a world where the rabbits could never die or get ill, in other words nothing would stop them constantly reproducing..
Suppose a newborn pair of rabbits (one male and one female) are put in a field. These rabbits take a month to become sexually mature, after which time they produce a new pair of baby rabbits, one male and one female.
These babies will take a month to mature, so although in the third month the mature rabbits can produce yet another pair of baby rabbits, the other pair will only be ready in the fourth month to reproduce. The pattern continues in this fashion and every month there are increasing numbers of rabbits. - 1,1,2,3,5, 8,13_ And so the Fibonacci number sequence emerges from the breeding habits of rabbits.There is a strong interrelationship between the numbers in the Fibonacci sequence. For a start, you get the next Fibonacci number by adding the two previous ones together, so there is already a relationship between them. For example, if you square the first hundred Fibonacci numbers and add them together it is the same result as the hundredth Fibonacci number times the 101st Fibonacci number. It is curious that these connections between the squares of Fibonacci numbers connect with later numbers in the sequence and in fact, there are quite a lot of these weird connections between the numbers. For example, if you have the 100th Fibonacci number and you want to find out the 300th Fibonacci number there is a very simple way to do it. You cube the 100th Fibonacci number, multiply by 5 and then add 3 times the 100th Fibonacci number. This will give the answer to what the 300th Fibonacci number is. There are many formulas linked with the Fibonacci sequence.
Melvyn Bragg Newsletter 30th November 2007

Liz Blackburn and the story of Telomeres

A biography of Liz Blackburn one of the pioneers in research on telomeres has been written
This describes her development in science form Melbourne to Cambridge and then California.
She trained in the techniques of DNA analysis and then embarked on her studies of the chromosome ends, telomeres.
Telomeres are important in ageing and possibly cancer. She transformed curiosity into hard science.
Elizabeth Blackburn and the story of Telomeres: deciphering the ends of DNA by Catherine Brady
MIT Press 2007

Starvation, tumour formation and molecular biology

It is always satisfying when the hints developed by epidemiology ae shown in experiments to be true.
Some epidemiological observations ( e.g. smoking and cancer of the lung and jumping from the 22nd floor of a building is fatal) stand in their own right.
Others point the direction
One such indicator is that starvation reduces the chances of tumour development.
Lee and his colleagues in a difficult paper show a relationship between tumour development and energy starvation.
Tumour formation is a process in which the normal control mechanisms are lost. A serine/threonine kinase ( mTOR) is central to a diverse range of cellular processes important in growth and proliferation. mTOR is increased in a number of malignant processes. There are two forms of mTOR with different regulatory functions. The tumour suppressors TSC1 and TSC2 regulate mTOR.. Loss of TSC1 or TSC2 leads to a tumour called hamartoma syndrome which is a none malignant growth.
By phosphorylating TSC2, the low energy response mediator AMPK inactivates mTOR dependent growth and proliferation. This phosphorylation of TSC2 has a protective role against energy starvation mediated apoptosis ( cell death ). Other substrates phosphorylated by AMPK lead to anabolic processes being inhibited and catabolic processes being activated.
AMPK also protects the cell cycle from stress by phosphorylation of the gene p53. Protein synthesis is also prevented.
Both energy starvation and DNA damage lead to p53 activation. mTOR activity increases p53 synthesis and activation in response to both glucose starvation and DNA damage. There is phosphorylation of p53 . p53 is a potent activator of apoptosis.
By means of the AMPK-TSC-mTOR pathway , p53 forms a negative feedback loop which keeps its own synthesis in check. Cells that cannot inhibit mTOR have increased p53 activity when activated.
Lee et al (2007) Constitutive mTOR activation in TSC mutants sensitises cells to energy starvation and genomic damage via p53. The EMBO Journal vol 26, 4812-4823.

Energy intake and the menstrual cycle

Women’s weight and body composition is significantly influenced by the female sex-steroid hormones.
Concentrations of these hormones change through the menstrual cycle and influence energy bomeostasis. A review by Davidsea et al (2007 ) reviews the scientific literature on the relationship between hormonal changes across the menstrual cycle and energy balance, and whether these changes influence weight loss in women. In the luteal phase of the menstrual cycle it appears that women’s energy intake and energy expenditure are increased and they experience more frequent cravings for foods, particularly those high in carbohydrate and fat. compared to the than during the follicular phase.
The follicular phase of the menstrual cycle includes menstruation , during the first 14 or so days, with processes leading to ovulation under the control of Follicle Stimulating Hormone and later in this first 14 days oestrogen.
After ovulation the luteal phase lasts for another 14 or so days. The ovum has been expressed into the Fallopian tubes and conception is possible. During this phase Luteinising Hormone and progesterone concentrations increase. There is also a slight increase in body temperature.
These profound hormonal changes are liable to have metabolic and nutritional consequences. Amenorrhoea, absence of periods is a feature of profound weight loss.
The authors of the review suggest that studies are needed to assess the weight loss outcome of tailoring dietary recommendations and the degree of energy restriction to each menstrual phase throughout a weight management program, taking these preliminary findings into account.
A worthy thought . It is interesting that women often accumulate weight during pregnancy and possibly also in the post menopausal period of their lives.
Davidsea L et al (2007 ) Impact of the menstrual cycle on determination of energy balance : a putative role in weight loss attempts. International Journal of Obesity. Vol 31, 1777-1785.