Supplements, vascular risk and homocysteine

Supplements to lower homocysteine concentration disappoint again
Epidemiological and genetic studies show a clear association between high serum concentrations of homocysteine and a higher risk of cardiovascular disease. So for more than a decade, researchers have been trying to reduce the risk of cardiovascular disease by giving people homocysteine lowering supplements of B vitamins and folic acid. Four large trials have already reported disappointing results. Now a fifth finds that B vitamins and folk acid don’t prevent cardiovascular disease, even in high risk patients with chronic, renal failure. Once again, the supplements brought down the participant’s homocysteine concentrations but not their risk of death , heart attack, stroke , or amputation .
No one can explain why the supplements don’t work in large trials, although one explanation is the attenuating effect of fortifying cereals with folic acid.
BMJ 22nd September 2007, supplements to lower homocysteine concentrations disappoint again vol 335, p587
Jamison et al JAMA 2007, Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease. Vol 298, 1163-1170.
Homocysteine is a non-protein-forming sulphur amino acid whose metabolism is at the intersection of two metabolic pathways: remethylation and transsulfuration . In remethylation, homocysteine acquires a methyl group from N-5-methyltetrahydrofolate or from betaine to form methionine. The reaction with N-5-methyltetrahydrofolate occurs in all tissues and is vitamin B]2 dependent, whereas the reaction with betaine is confined mainly to the liver and is vitamin B[2 independent. A considerable proportion of methionine is then activated by ATP to form S-adenosylmethionine (SAM). SAM serves primarily as a universal methyl donor to a variety of acceptors. 5-adenosyl homocysteine (SAH), the by-product of these methylation reactions, is subsequently hydrolysed, thus regenerating homocysteine, which then becomes available to start a new cycle of methyl-group transfer. This hydrolysis is a reversible reaction that favours the synthesis of SAH and that elevated cellular concentrations of this metabolite are likely to accompany all forms of hyperhomocysteinemia.
.In the transsulfuration pathway, homocysteine condenses will form cystathionine in an irreversible reaction catalyzed by the pyridoxal -5'- phosphate (PLP)-containing enzyme -cystathionine. β-synthase.is hydrolyzed by a second PLP-containing enzyme, γ-cystathionase, to cysteine and α-ketobutyrate. Excess cysteine is oxidized to taurine excreted in the urine.
Thus, in addition to the synthesis of cysteine, this transulfuration pathway effectively catabolises excess homocysteine which is not required for methyl transfer.
Selhub J 1999 Homocysteine vol 19, 217-8
Could it be that the emphasis is on the wrong system. What if the transsulfuration enzyme reaction system is lacking. There is synergy between the two pathways and this is nutritionally regulated. The addition of folic acid or other B vitamin may be of secondary rather than primary import.

loss of smell, anosmia

If one had to chose a sensory faculty to loose, smell would rank above sight or hearing. Neverthe less it is an important loss. It is called anosmia and is said to affect 2 % of the population. Nevertheless few clinicians are interested in this problem. Such olfactory disorders may be secondary to nasal polyps. Damage to the nerves supplying the nose and viral infections are other causes.
Watts G 2007 Scent trials British Medical Journal 335, pp588-9

Benefits of education on exclusive breast feeding rates

The World Health Organisation and the American Academy of Pediatrics advocate exclusive breast feeding for the first 6 months and partial for up to 1 to 2 years.
The best way to achieve this has still to be identified. In a paper from Singapore
Su and colleagues have studied the effect of antenatal breast feeding education compared with routine hospital car (Su et al 2007, Antenatal education and postnatal support strategies for improving rates of exclusive breast feeding randomised controlled trial British Medical Journal vol 335, 596-9
The combination of antenatal breast feeding education and post natal support significantly improve the rate of mothers breast feeding their babies.
All of which confirms the benefit of education and support in nutrition. Mothers are particularly sensitive to advise to care for their baby.

Coordinated series of papers on Child Poverty

Poverty and the impact on children is a global problem.
It is impossible to look at pictures of beautiful youngsters from anywhere in the world and not to feel a strong sense of protection and hope for their future. Of course there is also the adage “the trouble with a kitten is that it grows into a cat”. The adult population has problems of its own.
Poverty however can compromise child development in so many ways. A remarkable enterprise is being conducted by 235 scientific journals around the world to draw attention to the theme of poverty and human development. Amongst these are
New York Academy of Sciences Special Annals Volume which has with typical generosity made articles available on line for open access. These include articles on Tuberculosis, HIV, hookworm, education and access to health care.
BMJ 2007, 27th October has an issue- Health in an unequal world devoted to the same subject. This includes Equitable access to health care ,including teenagers, poverty in Liverpool, school feeding programmes, Malaria and infant health .Articles are available on line.
The Lancet has a series of papers on this topic over a number of weeks.
This is true nutrition. Here are complex political, cultural , agricultural and nutritional problems. With millions dying in the sub African Sahara from HIV, tuberculosis and malaria the fate of the next generation in these countries is very indeterminate. The eldest child rears the others. This is far from ideal.

cancer and enzymes

Cancerous process do not by their very nature necessarily follow the metabolic pathways of the normal tissues.
The changes in the genome in cancer are becoming clearer. Such gene changes must by accompanied by enzyme changes. Two reviews look at two important enzyme groups which are important in cell biochemistry , proteases and fatty acid synthase.
Proteases have long been associated with cancer progression because of their ability to degrade extracellular matrices, which facilitates invasion and metastasis. However, recent studies have shown that these enzymes target a diversity of substrates and favour all steps of tumour evolution. Unexpectedly, the post-trial studies have also revealed proteases with tumour-suppressive effects. These effects are associated with more than 30 different enzymes that belong to three distinct protease classes.
Carlos Lopez-Otin and Lynn M. Mutrisian Emerging roles of proteases in tumour suppression Nature Reviews Cancer , 2007, vol 7, 800-808
There is a continued interest in the role of, (a key lipogenic enzyme which catalyses the terminal steps in the de novo biogenesis of fatty acids) in cancer pathogenesis. Tumour-associated fatty acid synthase, by conferring growth and survival advantages rather than functioning as an anabolic energy-storage pathway, appears to accompany the natural course of most human cancers. Recent work on the links between fatty acid synthase and well-established cancer-controlling networks begins to show that there is role for fatty acid synthase in the cancerous process. This must have metabolic consequences.
Javier A. Menendez and Ruth Lupu Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis Nature Reviews Cancer 207, vol 7, 765-777
Whilst such studies do not have immediate relevance to Nutrition, one day these findings will be translated into clinical care say in the anorexia of malignancy.

Dave Kritchevsky, a song on Fiber

My friend David Kritchevsky died this year. He had so many talents including being a superb scientist, with an encyclopaedic knowledge of nutrition and as a speaker and teacher composer of songs on nutrition .
This is an example.

F.I.B.E.R.
Tune: Mother
F is for the increased weight of feces
I is for intestinal milieu
B is for the gut bacterial action
E is how the enzymes work for you
R is for some useful explanation
of how these factors work for you and me.
Put them all together they spell "FIBER" Which leads to better health as all can see.
Fiber
Tune: Swanee
Fiber
How we need you, how we feed you
Bulky old fiber.
Cut transit time with ease And you can cure all Heart diseases and diabetes
Fiber - binding cholanoic acids Sticky old fiber
You'll live to be a hundred and six If you stay on your fiber kicks.

Book review , a history of British food

British Cooking has received a great deal of opprobrium over the recent years. Many look to the continent for good cooking. Meanwhile undisturbed by this reputation every day delicious dishes and meals are been served in Britain over the centuries..
Cookery books are major sellers, being of universal interest. They are the recordings of how food was prepared and reflect the cooking practices of the era in which the book was written. Cookery books in English are to be found from the 14th century from the cooks serving Richard II. Through out the ages these writers emphasise the joys of cooking rather than buying ready made meals.
Kate Colquhoun has written a history of British Cooking through the ages. This account starts in the medieval ages and comes to modern times.
Taste, The story of Britain through its cooking Bloomsbury
Worth having and reading

Watson and Venter have written their autobiographies

Life at the top of any intellectual discipline is not necessarily a kindly experience. The very bright can be bold brash characters.
Two men who have radically changed our knowledge of genetics are James Watson and Craig Venter.
Watson and Crick were the first to adequately describe DNA and in doing so transform our understanding of biology.
Craig Venter organised a privately funded project to decode the human genome.
Each have written an account of their lives and experiences.
Craig Venter , A life decoded: My genome: My life
Allen Lane
James Watson Avoiding boring people. And other lessons from a life in science.
Oxford University Press
Well reviewed and worth looking at.

Pubertal growth

The onset of puberty is a wonderful event for the child if not the parents. The curiosity is why it happens at this age. Why is the latent growth delayed. It is also interesting that the age of puberty and the so called growth spurt varies form child to child. Some children continue growing long after others and after a slow start grow more that expected.
Indian, Japanese and US children have similar growth patterns up to the age of 9 years. Thereafter a growth gap develops during the remaining years of growth between the first two nationals and the US adolescents. It is not clear whether this difference is environmental or genetic. The Indian and Japanese diet is largely cereal-derived and there may be dietary deficiency or dietary antinutrients which cause the lack of growth. A survey by the Japanese Ministry of Education in 1992 of 700 000 children aged between 4 and 18 years showed they had grown significantly in height compared with their parents. Boys aged 13–14 years old were 9.5 cm taller and 9 kg heavier than their parents at the same age. At 17–18 years these Japanese in 1992 were 5 cm taller than 30 years ago. Much of this difference was in leg length.
In the Netherlands, there is a tradition of monitoring children’s height that goes back to the 19th century. During the last century and the early part of this century differences of 5–11 cm at various ages were noted between those children whose fathers had a ‘low’ as compared with a ‘high’ occupational status. This gap is now reduced to differences of 1–3 cm. Similar reduction in height differentials between socially and economically disadvantaged and rich children have been observed in India. A British tradition, unproven except in folklore, is that the child’s height at 2 years 6 months is half that of the final growth achievement.
A curious feature of the development of the stunted child is the anatomy of the deficient height. This may be the sitting height, that is, coccyx to top of head or standing height where leg length is important. In stunted USA blacks and Australian Aborigines the sitting height is deficient; in Japanese, standing height is deficient and in Indians the deficit is symmetrical. Possibly some complicating micronutrient is deficient or the timing of the deficiency at some vulnerable period occurs primarily affecting trunk or leg growth.