alcohol metabolism

Alcohol Consumption and Cardiovascular Health PDF Print E-mail

Moderate ethanol ingestion and cardiovascular protection: From epidemiologic associations to cellular mechanisms.

J Mol Cell Cardiol. 2011 Oct 23.

While ethanol intake at high levels (3-4 or more drinks), either in acute (occasional binge drinking) or chronic (daily) settings, increases the risk for myocardial infarction and stroke, an inverse relationship between regular consumption of alcoholic beverages at light to moderate levels (1-2 drinks per day) and cardiovascular risk has been consistently noted in a large number of epidemiologic studies. Although initially attributed to polyphenolic antioxidants in red wine, subsequent work has established that the ethanol component contributes to the beneficial effects associated with moderate intake of alcoholic beverages regardless of type (red versus white wine, beer, spirits). Concerns have been raised with regard to interpretation of epidemiologic evidence for this association including heterogeneity of the reference groups examined in many studies, different lifestyles of moderate drinkers versus abstainers, and favorable risk profiles in moderate drinkers. However, better controlled epidemiologic studies and especially work conducted in animal models and cell culture systems have substantiated this association and clearly established a cause and effect relationship between alcohol consumption and reductions in tissue injury induced by ischemia/reperfusion (I/R), respectively. The aims of this review are to summarize the epidemiologic evidence supporting the effectiveness of ethanol ingestion in reducing the likelihood of adverse cardiovascular events such as myocardial infarction and ischemic stroke, even in patients with co-existing risk factors, to discuss the ideal quantities, drinking patterns, and types of alcoholic beverages that confer protective effects in the cardiovascular system, and to review the findings of recent experimental studies directed at uncovering the mechanisms that underlie the cardiovascular protective effects of antecedent ethanol ingestion. Mechanistic interrogation of the signaling pathways invoked by antecedent ethanol ingestion may point the way towards development of new therapeutic approaches that mimic the powerful protective effects of socially relevant alcohol intake to limit I/R injury, but minimize the negative psychosocial impact and pathologic outcomes that also accompany consumption of ethanol.

Metals in Wine PDF Print E-mail

Biol Trace Elem Res. 2011 Apr 9. [Epub ahead of print]
Metals in Wine-Impact on Wine Quality and Health Outcomes.
Tariba B.
Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10001, Zagreb, Croatia, This e-mail address is being protected from spambots. You need JavaScript enabled to view it .
Metals in wine can originate from both natural and anthropogenic sources, and its concentration can be a significant parameter affecting consumption and conservation of wine. Since metallic ions have important role in oxide-reductive reactions resulting in wine browning, turbidity, cloudiness, and astringency, wine quality depends greatly on its metal composition. Moreover, metals in wine may affect human health. Consumption of wine may contribute to the daily dietary intake of essential metals (i.e., copper, iron, and zinc) but can also have potentially toxic effects if metal concentrations are not kept under allowable limits. Therefore, a strict analytical control of metal concentration is required during the whole process of wine production. This article presents a critical review of the existing literature regarding the measured metal concentration in wine, methods applied for their determination, and possible sources, as well as their impact on wine quality and human health. The main focus is set on aluminum, arsenic, cadmium, chromium, copper, iron, manganese, nickel, lead, and zinc, as these elements most often affect wine quality and human health.

Levels of histamine and other biogenic amines in high-quality red wines. PDF Print E-mail

Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2011 Apr;28(4):408-16. Epub 2011 Feb 16.
Levels of histamine and other biogenic amines in high-quality red wines.
Konakovsky V, Focke M, Hoffmann-Sommergruber K, Schmid R, Scheiner O, Moser P, Jarisch R, Hemmer W.
FAZ - Floridsdorf Allergy Centre, Franz Jonas Platz 8/6, A-1210 Vienna, Austria.
Biogenic amines in wine may impair sensory wine quality and cause adverse health effects in susceptible individuals. In this study, histamine and other biogenic amines were determined by HPLC after amine derivatisation to dansyl chloride conjugates in 100 selected high-quality red wines made from seven different cultivars. Amine levels varied considerably between different wines. The most abundant amines were putrescine (median = 19.4 mg l(-1), range = 2.9-122), histamine (7.2 mg l(-1), 0.5-26.9), and tyramine (3.5 mg l(-1), 1.1-10.7), whereas lower levels were found for isoamylamine (median = 0.25 mg l(-1)), phenylethylamine (0.16 mg l(-1)), cadaverine (0.58 mg l(-1)), spermidine (1.8 mg l(-1)) and tryptamine (0.06 mg l(-1)). Positive correlations were observed between isoamylamine and phenylethylamine, and between histamine, putrescine and tyramine levels. Amine concentrations were similar in all wine cultivars except Pinot noir and St. Laurent wines, which showed significantly higher tryptamine and cadaverine levels. The results indicate that levels of histamine and other biogenic amines may vary considerably between red wines independent of grape variety and that high amounts can also be found in high-rated wines. Adopting a legal histamine threshold level of 10 mg l(-1) in the European Union, as formerly introduced in other countries, would have excluded 34% of the investigated wines from the market.
PMID: 21337238 [PubMed - in process]

Winedoctors and AIM PDF Print E-mail

This article has been collated in response to a series of

dialogues between members of AIM Social Scientific

and Medical Council and The International Scientific

Forum on Alcohol Research. Gordon Troup of Monash

University, invited his mathematician colleague,

Mike Deakin to look at the maths and statistics in the

literature regarding the rate of metabolism of alcohol

and blood alcohol concentration, much of which

dates mainly from the 1950’s and indeed back to the

19th century.

The mechanisms of how alcohol is broken down

We know that alcohol (ethanol), a small water

soluble molecule, can be absorbed unchanged

along the whole length of the digestive tract and

that absorption takes place rapidly from the stomach

(about 20%), and most rapidly from the small gut

(about 80%).

We know too, that the rate of absorption after

drinking is affected by several factors, such as the

concentration and volume of liquid taken with the

alcohol, whether drinking with or without food, the

rate of gastric emptying and individual variations,

such as ethnicity, height, weight and sex.

After absorption into the blood-stream, alcohol is

distributed quickly throughout the total body water.

Approximately 90% is broken down into carbon

dioxide and water at a steady rate, the remainder is

converted to acetate (harmless) – and then into CO2,

H2O and energy (this is known as the Krebs cycle) and

excreted via the normal routes!

Myths and realities – can you speed up the rate of

metabolising alcohol?

An interesting study in 1972 by G PAWAN (Metabolism

of alcohol (ethanol) in man Proc. Nutr. Sac. (197z),

31, 83) investigated claims that taking vitamins and

sugars can increase the rate of ‘sobering up’ in man

and laboratory animals. He analysed the effects of

caffeine and strong black coffee, dietary factors,

physical exercise, environmental temperature

changes, thyroid hormones, oxygen therapy and

various drugs on the rate of metabolising alcohol in


Physical exercise - Despite the increased pulmonary

ventilation, sweat loss and general rise in metabolic

rate, physical exercise did not significantly affect the

rate of alcohol metabolism.

Vitamin supplements - It was concluded that in

these normal, well-nourished individuals, vitamin

supplementation did not affect the rate of alcohol


Caffeine and strong black coffee - Caffeine (50mg)

and two cups of strong, unsweetened black coffee

were given one hour after the dose of alcohol; no

effect on the rate of alcohol metabolism was seen.

The metabolism of alcohol and its effect on estimating blood alcohol


excreted unchanged in the

urine, expired air and sweat.

The main site of metabolism of

ethanol is the liver, although

some other tissues, for

example kidney, muscle, lung,

intestine and possibly even the

brain, may break down smaller

quantities. It is thought that

the rate-limiting step in the

breakdown of alcohol is its

conversion to acetaldehyde

(toxic), a reaction catalysed by

the zinc-containing enzyme,

alcohol dehydrogenase


The acetaldehyde formed in

the first oxidative step in the

metabolism of ethanol, is then

Metabolism of ethanol


Significantly, Pawan found that both a long term

high fat diet and a starvation diet slowed the bodies

ability to break down alcohol by 20%. This was

believed to be due to a depletion of enzymes (being

inhibited by free fatty acids) and an enhancement

of the reduced redox state of liver cells. However,

eating a balanced meal before, during or even after

drinking does help the metabolism of alcohol. Food,

and particularly carbohydrate, retards absorption

and blood concentrations may not reach a quarter of

those achieved on an empty stomach.

An interesting study by Dr Wayne Jones et al

explored food-induced increase in the rate of

disposal of ethanol. Ten healthy subjects ate a meal

5 hours after drinking when the post-absorbtive

phase of ethanol metabolism was well established.

The mean rate of disappearance of alcohol from the

blood was increased by between 36 and 50%. The

results demonstrate that eating a meal boosts the

rate of disappearance of ethanol from the blood,

and the increase was seen after 3 different doses

of alcohol. (Jones AW, Jönsson KÅ. Food-induced

lowering of blood-ethanol profiles and increased

rate of elimination immediately after a meal. Journal

of Forensic Sciences 1994;39:1084-93).

No sugars, with the exception of fructose, affected

the rate of metabolism of alcohol.


Responsible drinking guidelines are lower for women

for good biological reasons.Very little alcohol enters

fat because of fat’s poor solubility. Blood and tissue

concentrations are therefore higher in women, who

have more subcutaneous fat and a smaller blood

volume, than men, even when the amount of alcohol

consumed is adjusted for body weight. Women

also may have lower levels of the enzymes alcohol

dehydrogenases (ADH) in the stomach than men, so

that less alcohol is metabolised before absorption.

Populations lacking gene to metabolise alcohol

As explained, alcohol metabolism, is catalysed by an

enzyme, acetaldehyde dehydrogenase (ADH). This

enzyme converts acetaldehyde to acetate, which

is a normal metabolite in humans and hence is non


Certain individuals, common in the Japanense

and some other Asians, have a defective aldehyde

dehydrogenase gene, ALDH2, which doesn’t

metabolise acetaldehyde as rapidly as normal. Thus,

a person who drinks too much builds up acetaldehyde

in their system and feels bad or is sick. This manifests

in Asians with the defected ALDH gene as a facial

flush as they drink. These responses make drinking

any alcohol unpleasant, as well as toxic.

Comments of Mike Deakin School of Mathematics

Monash University, Victoria 3800 Australia

One would think it a relatively simple matter to

discover the rates of alcohol clearance from the

human body, and in a sense this is the case. However,

if one looks for reputable sources backed up by wellconducted

experiments, then the search suddenly

becomes more difficult!

However, the book Drink, Drugs and Driving by

H. J. Walls and A. R. Brownlie, 2nd Ed. (London &

Edinburgh: Sweet & Maxwell, 1985) is accessible and

authoritative. The first author is a former director of

the Metropolitan Police Forensic Science Laboratory

(UK) and the second a solicitor of the Edinburgh

Supreme Court.

Sensibly, these authors do not try elaborate

mathematical modeling or fancy curve-fits. Rather

they supply 2 straight-lines that summarise the data

excellently well. The rule is this:

For a BAC of 0.15 or greater, the elimination rate is 0.02

per hour, for lower BACs, 0.015 per hour.

Although this source is authoritative and commands

respect, it is not primary, but rather draws on two

other sources,

The rule just given is based on data from a German

study: Gerchow & Steigleder’s Blutalkohol (1961); it

is partially supported by an English study (“Effect of

small doses on a skill resembling driving”, Medical

Research Council Memorandum No. 38, HMSO,

London, 1959). (This source considers only lower

levels of BAC, but agrees with the figure of 0.015. It

should, of course, be borne in mind that the figures

given are averages only.

The two editions of Walls and Brownlie’s book differ in

some places, and the first edition includes references

not cited in the second. Regrettably, most of these

are likewise difficult of access.

Blood Alcohol Content Metabolised at 0.01 per


Comments by Gordon Troup School of Physics,

Monash University, Victoria 3800 Australia

The difficulties in finding satisfactory articles were

great, and there were difficulties even in the articles.


An article by in ‘Nature’ by Jacobsen [1] in1952 refers

to work by Mellanby (1919 ) and Widmark (1922-35),

To quote from Jacobsen: “Both studies found in man

an average of 15 mgm. percent alcohol disappears

from the blood per hour, the range being 10-20 mgm.

per cent.”

So we now know when respectable work started!

Again, to be brief as to respectable work and its

interpretation, the best reference in English is by

Walls and Brownlie (1985) [2].We give a reference in

German, by Ebbel and Schleyer (1956).

Since the respectable works agree on the .015 rate of

recovery, to work on a .01 rate seems a good margin of

safety for people to to judge by. Remember, This is for

MEN. If necessary, experts could re-examine the old

references with regard to methods and conclusions

in the light of modern techniques and analytical

developments. In the meantime, it is suggested that

we continue with the .01 rate.

Lynn Gretkowski MD comments

‘Regardless of citations this “clearance number” is

merely now only a number that is generalisable. The

individual pharmacodynamics of alcohol elimination

take into account liver weight, gender, ethnicity, type

and density of alcohol dehydrogenase receptors,

rate at which alcohol is consumed, associated

consumption of food and activities among many

other factors. The reason no new calculations exist

from the mid-nineteenth century onward is likely

largely a reflection of that. It seems as though this is

about as specific as it can be to be clinically useful’.

Dr Erik Skovenborg finds that

‘Very little has been added to the Widmark formula

during the years. One aspect, however, investigated

by a pupil of Widmark has found inter individual

variations in the ethanol metabolism: (Jones AW.

Interindividual variations in the disposition and

metabolism of ethanol in healthy men. Alcohol


Dr David Van Velden cited:

‘The ABC of alcohol was published in the BMJ Volume

330, 8 January 2005 ( The 4th edition of the

ABC of Alcohol, became available in February 2005.

According to this article alcohol is removed from

the blood at a rate of about 3.3 mmol/hour (15 mg/



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Glaxo Halts Resveratrol Study PDF Print E-mail

Glaxo Halts Resveratrol Study

By Darryl Isherwood & Darryl R. Isherwood
Published May 05, 2010

GlaxoSmithKline (GSK) halted a clinical trial seeking to explore the benefits of a chemical found in red wine.
The trial was studying the effects on cancer patients of a drug containing a reformulated version of resveratrol. Glaxo acquired the drug as part of its 2008 purchase of Sirtris Pharmaceuticals.
Glaxo halted its trial of the drug on patients with multiple myeloma  after several patients developed nephropathy, a condition that can cause kidney failure.
A Sirtris official told Dow Jones that the condition is common in multiple myeloma patients, so its cause is unclear.
Resveratrol has been hailed as an anti-aging miracle drug, but recently scientists have begun to question the effectiveness. Resveratrol is thought to work by activating enzymes in the body called sirtuins.

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