Alcohol toxicity - not every drinker
Dr Victor Preedy, head of the Nutritional Sciences Research Division
at King’s College London’s Genomics Centre, asked why some
drinkers can OD on alcohol with little apparent toxic effect whereas
others cannot.
It is generally believed that cirrhosis and brain damage are the most common
physiological results of alcohol misuse; in fact there is good evidence that
alcohol can affect a wide range of body systems. Alcoholic myopathy, characterised
by muscle weakness and loss of bulk, is five times more common than cirrhosis
and is arguably the most prevalent skeletal muscle disorder in the western hemisphere.
But, not every alcohol misuser will develop a disease.
The key lies in the way alcohol is metabolised. A major product of the metabolism
of alcohol is acetaldehyde. Acetaldehyde is normally oxidised to acetate, which
is not overtly toxic. This reaction is catalysed by aldehyde dehydrogenase, which
is where genes come into play. Depending on the individual’s genetic make-up,
the level of acetaldehyde resulting from a similar amount of alcohol will be
very different.
Parallel reactions in the metabolism of alcohol include the generation of free
radicals and oxidative imbalance, so dietary factors such as vitamin E are important
in counteracting the damaging effects of alcohol. Individual responses to alcohol
are due to a combination of genetics, diet and other lifestyle factors.
Why are some patients harmed by medicines and others are not?
Professor Munir Pirohamed of the Department of Pharmacology at Liverpool University
quoted some frightening statistics.
It is estimated that up to 65% of the patients in hospital at any one time are
there because of adverse drug reactions (ADRs). Around 28% of ADRs are easily
avoidable and probably over 70% could be avoided with correct prescribing practices.
The most common cause of ADRs is the prescription of multiple drugs that interact
with each other. It is common practice, for instance, to prescribe aspirin with
a non-steroidal drug when the combination is more dangerous than either drug
alone and, in most cases, less effective.
One dose size does not fit all. Individuals can have radically different dose
requirements and the effectiveness or otherwise of a particular drug depends
on getting the dose right. The medical profession needs strategies to personalise
drugs doses to individuals. There can be severe interactions between herbal medicines
and prescription drugs yet doctors seldom ask patients about, or note, herbal
and other alternative remedies they may be taking. Doctors need to educate their
patients to tell them about their drug regimes - and they need to educate themselves
to listen.
Of the UK population over 80, more than 60% is on warfarin, but it is very difficult
to titrate the correct warfarin dose for the individual patient. The warfarin
dose requirements of 54% of those over 80 could be determined by genetic tests,
but unfortunately for 46% the tests are not yet effective.
Genotype analysis is likely to be the way forward for determining drug dosage
of warfarin but there is still a long way to go.
Diet and individuality in detoxification
Dr Rosemary Waring, Reader in Human Toxicology at the University of Birmingham,
asked why it is that different people respond differently to diet and environmental
factors? Her research indicates that that the answer lies in a combination of
inborn susceptibility (genetics) and the precise cumulative input from the environment.
This leads to some interesting conclusions.
The answer to the perennial question ‘is coffee bad for me?’ depends
on the individual’s acetylator status. Fast acetylators are not affected
by coffee whereas slow acetylators are. The UK population is split roughly 50/50
between fast and slow acetylators, so probably 50% of the customers of the local
Starbucks should not be there, as almost nobody knows their acetylator status.
Generalisations about diet and health are often hard to justify. For instance,
epidemiological cancer studies show no real benefit from the much hyped five
portions of fruit and vegetables. In some individuals fruit and veg enhance important
enzymes, whereas in other cases they inhibit them. Certain foods do have widespread
and detectable benefits. Onions and bananas are good for the hearts of most people.
Allergic responses can be made worse by the presence of sulphite (often found
in food preservatives). Patients with allergies frequently have high urinary
sulphite levels, which may reflect an inability (either genetically or environmentally
induced) to oxidise sulphite to non-toxic sulphate.
Blood group diets
Drs Tom Greenfield and Laura Power both discussed
blood group diets but this has been covered in some detail in Dr
Greenfield's article in the
January 04 Foods Matter.
More information can also be had at www.dadamo.com where Dr Greenfield has a regular blog.
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