I am one of 50% of Asians that are plagued with the "Asian Flush." 
I'm referring to the condition where after at least one alcoholic
drink is ingested, my complexion becomes flushed, my heart beats
faster, my temperature goes up (my skin radiates heat), and I
ultimately resemble a red cherry!  After doing my own research, I'm
familiar with the technical understanding of my alcohol flush reaction
(the concept that I lack the enzyme, aldehyde dehydrogenase, which
breaks down acetylaldehyde…).

My Profile:  I am a social drinker (a few drinks once a week such as
three beers on a Saturday night), stocky set.
 
Regarding this phenomenon, I've read many research articles and
postings such as the following:

	http://oregonstate.edu/groups/chronicle/issues/Winter2001/articles/redface.cfm
	http://www.goaskalice.columbia.edu/2327.html
	http://www.inform.umd.edu/News/Diamondback/archives/2002/10/10/news6.html

I am knowledgeable about the "Red Face" or "Asian Flush" phenomenon,
but I would like some treatment/preventative tips.
  
Here are my following questions:

1)  What preventive measures or treatments are there, such as taking a
pill before drinking alcohol, etc,. to lessen my red flush reaction? 
(*I already know the obvious answer would be to drink less or not at
all, but I would like other credible ideas that lead to noticeable
results.)

2)  I have heard that it is possible that an antihistamine or aspirin
will cut down or prevent the flush, but does this work and is it safe?

Thanks so much!
Your Beet Red Friend

danausch

Hello danausch

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 enzyme’s 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:
http://www.ajcn.org/cgi/content/full/75/4/616 

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
acetaldehyde.
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.
Abstract: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8488989&dopt=Abstract
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
alcohol-hypersensitive Japanese.
By Inoue K, Kera Y, Kiriyama T, Komura S., published in Japanese
Journal of Pharmacology, 1985 May;38(1):43-8.  Abstract at:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4021229&dopt=Abstract
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
http://www.maripoisoncenter.com/ctr/9806_4methypyrazole.html

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
lot.

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
http://www.dhfs.state.wi.us/substabuse/Education/Teleconference/2002presentations/alcoholpharmacology051402.pdf

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.

---

Request for Answer Clarification by danausch-ga on 22 Sep 2003 13:20 PDT

Just to make things clear, to prevent or reduce flushing, I should 1)
Increase my sugar intake while drinking and 2) Ingest Niacin
vitamins/pills (while not taking aspirin).  Anything else that you
happen to come across?  No elaboration needed.  Thanks so much!

---

Clarification of Answer by tehuti-ga on 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.

Thanks for the detailed answer!

With regard to taking an antihistamine or aspirin prior to drinking -
just don't.  Mixing alcohol and medications can be quite hazardous, so
please be safe and don't do this!

As for the "flush", have you considered eating something starchy while
you're drinking?  Pretzels or party mix or some such?  I'm very pale
and become quite rosy when I'm drinking, but find that the effect is
lessened when I've eaten.  It seems to slow down the alcohol
absorbtion.

Good luck!

--Missy

I also get the "glow" mysely and, personally, eating only makes things
worse for me.  I just try not to eat so much and so close to the time
I know I might be having a drink as well as not eat during. (i usually
wait a good 3-4 hours)  I'm thinking the food just lets it sit in your
stomach longer makes it longer to run through your system.  And as for
the advice on taking niacin..I was reading another site that but i
don't know.  said it was either nicotinamide or niacinamide..not
niacin.    the site is:  www.askbird.com/cfs/aldehyde.htm  I don't
know what really works but the separating of food and alcohol seem to
work pretty well for me.

Howdy, I know this thread started a while ago, but i have the answer
to all your prayers.  Take a antacid (pepcid AC, zantac NOT tums,
etc.) and follow the directions on the box this will help immensely.

Just to add to the posting, I'm half asian, and have problems with the
flush and associated problems.  Eating has various effects sometimes
helping sometimes not, but is certainly not consistent.  I've found
that sugary drinks (margarita's, Mai-Tai's, etc) are the worse, and
generally give me a headache as well.  Wine and beer are next worst. 
Good quality vodka mixed with soda water or water (martini's also)
usually has pretty minimal effect--just a light flush instead of the
full Red Light effect.  I haven't tried the antacid solution.

I'm half asian also and the flush hits me pretty bad that I cant
engage in the activity.  Likewise vodka is proberly the best of the
lot, mixed perhaps with orange juice. Sugar doesnt seem to help and
maybe it worsens the situtation in my case. I might give the
suggestions in this thread a try, mega doses of nicican may work but
it is interesting to note the substance in itself causes flushing
also.  there is a no flush compound (Inositol Hexanicotinate) and i
Think megadosing with that (maybe not to frequently as it has its own
pros and cons could be a feasible solution.  The mutant genes cofactor
(NAD) is as far as i can interpret a compound of the supplements
niacic acid (causes the vasolidation), nicotimamade, both together
which make "nician".  To treat this symptom at the cause would be to
address the imbalance here but I think it's inherrently a very complex
arangement and it's not as simple an answer as suplementing one
missing vitimin. "oxidation of ethanol results in the transfer of
hydrogen to the co-factor NAD converting it to its reduced form NADH"

However there are potentially other ways that this symptom could be contained.

4-methpyrazole is an easy solution but it should be noted the drug
itself has some very nasty side effects.  Not to mention they
adminster it intravenously.  I would stay away from this one.

Some people mentioned substances that can bypass the first pass
process of alcohol (in the stomach) the first pass process is more
important to men than women as they have a lower water content.  As
mentioned the majority of the action happens in the liver anyhow so
the process would simply delay or stall acculimation of acetaldehyde
for a certain amount of time untill it all reaches the liver
eventually anyway.

Metabolism of ethanol:
While the ADH + NAD = NADH route is considered the primary route for
the breakdown of alcohol it should be noted that there other pathways
in which the substance can be processed.  The MEOS system is used
increasingly in those who often consume large ammounts of alcohol.  In
this case a much higher percentage (up to tenfold) of the substance is
metabolized through this route.  This is why some people with the
deficiency report that drinking more frequently reduces the flush
symptoms. An idea would be to take another substance that also uses
the MEOS system, priming or enabling it as a route of catalzisation as
a substitute to the ADH route. Another system exists in the large
intestine (ie colon) I believe this route is refered to as catalese
but I not sure.  The contribution of bacteria in gastronomical alcohol
matabolism is still controversial. Certain antibotics can increase
alcohol absorbtion in the intestine.

Reducing vasodilation.  I didnt look into this but certain precautions
(as mentioned above) can be taken to limit the extremity of flushing
in the face and other areas.


Id like to compile more information before testing any of the above
things (it's kinda like stabbing in the dark really) and get more
conclusive data on a whole range of things from the matobolism of
alcohol ALDH, MEOS and catalase, the mutant gene ALDH2,drug alcohol
interactivity, and the function of niacin and NAD to try and forumlate
a solution.

here's some linkage for all the above stuff
http://chemcases.com/alcohol/alc-13.htm
http://www.findarticles.com/p/articles/mi_m0CXH/is_1_23/ai_57050108
http://www.medhelp.org/NIHlib/GF-166.html
http://www.medicouncilalcol.demon.co.uk/handbook/hb_meta.htm

has anyone tried the antacid? Does it work? When do you take it?