Bruce Ames, a highly respected scientist of worldwide fame from
Berkely, co-authored a review of the possible use of megavitamin
therapy in a number of inherited conditions. Among these he discusses
the one you cite. He found papers in the scientific literature
showing that the mutation responsible affects only one amino acid in
the part of the aldehyde dehydrogenase molecule that is responsible
for binding to the enzymes cofactor, NAD (nicotinamide adenine
dinucleotide). As a result the enzyme becomes 150 times less
effective in binding NAD. Since the cofactor is needed to the enzyme
to do its job in metabolising acetaldehyde, the mutant enzyme is less
effective at doing that as well, with its activity being only 8% of
the non-mutant form. NAD is produced from the B-complex vitamin
niacin. Ames suggests that taking high doses of niacin could increase
the binding between enzyme and cofactor and thus increase the
efficiency of the mutant enzyme.
The review is: High-dose vitamin therapy stimulates variant enzymes
with decreased coenzyme binding affinity (increased Km): relevance to
genetic disease and polymorphisms by
Bruce N Ames, Ilan Elson-Schwab and Eli A Silver, published in
American Journal of Clinical Nutrition, Vol. 75, No. 4, 616-658, April
2002. You can read the full text of the article at:
Taking fructose or glucose might help. A study in rats found that
supplementation of diets with fructose or glucose increased the
elimination of alcohol, but without affecting the alcohol
dehydrogenase activity. It is possible that these sugars stimulate
another metabolic pathway that does not result in the production of
Dietary carbohydrate accelerates ethanol elimination, but does not
alter hepatic alcohol dehydrogenase. By Keegan A, Batey R., published
in Alcohol Clin Exp Res. 1993 Apr;17(2):431-3.
Hmmm, and since fructose is found in fruit, perhaps some daiquiri
The drug 4-methpyrazole is a strong inhibitor of alcohol
dehydrogenase, and was found to prevent the accumulation of
acetaldehyde and related responses such as flushing in Japanese men.
Suppression of acetaldehyde accumulation by 4-methylpyrazole in
By Inoue K, Kera Y, Kiriyama T, Komura S., published in Japanese
Journal of Pharmacology, 1985 May;38(1):43-8. Abstract at:
It is used to treat poisoning by ethylene glycol and methanol.
However, I cannot see it being used simply for social reasons, since
it is extremely expensive: 4-methylpyrazole is available in a dose
pack of 4-1.5ml vials of a 1g/ml solution. This should be enough for
the entire course of treatment for one patient. The cost (in 1998) of
one dose pack however is $4000.
Clinical Toxicology Review, June 1998
Since flushing is due to dilation of blood vessels, it might well be
useful, while drinking, to avoid other things that can cause this
effect, for example heat (hot atmosphere, being too warmly dressed)
and spicy food.
Aspirin has been found to increase blood alcohol levels in some
individuals. The mechanism is that it inhibits the activity of
gastric alcohol dehydrogenase, as reported for example in: Mechanism
of the aspirin-induced rise in blood alcohol levels by Gentry RT,
Baraona E, Amir I, Roine R, Chayes ZW, Sharma R, Lieber CS, published
in Life Sciences 1999 Oct 29; Vol. 65: pp. 2505-12.
Abstract at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10622235&dopt=Abstract
Antihistamines and acetaminophen are also reported to decrease the
activity of this enzyme. However, this effect only operates on the
so-called first-pass metabolism, through which some of the alcohol
is metabolised in the stomach. First-pass metabolism varies among
individuals, and is much lower in woman generally than in men.
Therefore, the effect of aspirin and other such agents will vary a
More importantly, even when there is no inhibition, only about 8% at
most of the alcohol is metabolised in this way. The rest of the
alcohol reaches the liver where it is metabolised by liver alcohol
dehydrogenase to acetaldehyde. I have not found any reports of aspirin
inhibiting liver alcohol dehydrogenase, therefore I do not see how
aspirin would affect the overall alcohol metabolism, and thus the
production of acetaldehyde, to any significant degree.
Therefore, I do not see how aspirin would help to prevent flushing.
Flushing is one of the side effects of high levels of acetaldehyde,
due to acetaldehyde causing the blood vessels to dilate. The
inhibition of gastric alcohol metabolism will only make more available
to reach the liver. There it will be metabolised to acetaldehyde by
liver alcohol dehydrogenase, which does not seem to be affected by
aspirin etc (at least, I was unable to find any papers to that effect
in the medical literature).
Moreover, as missy already said, combining aspirin and alcohol is not
a good idea. Aspirin irritates the stomach, and so does alcohol, and a
combination of the two is thought to increase the risk of stomach
ulcers. Also, both aspirin and alcohol inhibit blood clotting, so in
combination can increase the risk of dangerous levels of bleeding in
general and also of the stomach ulcers.
See, for example, Alcohol, pharmacology and neurobiology, by Michael J
Bohn, University of Wisconsin
OTC antihistamine preparations in the US, as far as I am aware, tend
to be first-generation antihistamines; the sort that make you sleepy.
Add that effect to the neurological effect of alcohol, and you get
someone walking round in a daze, highly prone to accidents.
Search strategies on Google and PubMed ( http://www.nlm.nih.gov/ )
1. "aldehyde dehydrogenase" Asians alcohol treatment
2. "aldehyde dehydrogenase" flushing
3. "alcohol dehydrogenase" aspirin
4. "alcohol dehydrogenase" inhibition
I hope this has given you the information you require, but please
request further clarification if necessary. Please note that I am
away from tomorrow (Friday) until Monday evening GMT.
Clarification of Answer by
22 Sep 2003 15:18 PDT
Hello again danausch,
The information I found is just a suggestion made by Bruce Ames. I
did not manage to find any studies attempting to prove or disprove
what he says. However, because Ames is respected in other areas of
science, I felt OK about transmitting his suggestion to you.
Nevertheless, I have no evidence that it will or will not work. Ames
suggests megadoses of niacin might have an effect on enzyme activity.
I know there are many mega-B-complex supplements, which would fulfil
this criterion, and there might be mega-niacin ones as well. Since
the B-complex vitamins, including niacin, are water-soluble, high
doses are relatively safe, because what is not used will be easily
excreted. Nevertheless, I would urge you not to go beyond the
suggested dosages of the supplement you purchase. I would guess the
best effect will be likely to occur if you take the supplement daily,
not just before you want to drink. Hopefully this might have a
longer-lasting influence on overall enzyme parameters.
With respect to the sugars, the study was done with fructose and
glucose. I know that sucrose (ordinary sugar) is metabolised to
glucose. Nevertheless, I would personally try using fructose or
glucose rather than just ordinary sugar. However, a high sugar intake
has its own associated minuses. My own strategy would be to increase
my intake of fruit, especially sweet fruit, since fructose is the
sugar that is found in fruit. Increased fruit intake will be of
enormous general benefit anyway. If you want to try supplementing
this, I would suggest trying to get hold of fructose or glucose powder
and take this before you hit the booze.