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01/23/2003
Mice and Men and Alcohol
Are you confused about all those recent studies relating to the
Atkins diet, new food pyramids and the beneficial health effects
of certain beverages? As for me, I’m ready for my Bloody Mary
made with vodka and V-8, thus combining the benefits of both
vegetables and alcohol. Or am I deluding myself? While the
controversy over the fatty Atkins approach versus the low fat
diets still rages, the evidence for a beneficial effect of moderate
alcohol consumption for men seems clearly established.
Roughly 30 years ago, one of my colleagues at Bell Labs decided
to switch careers and become a physician. He returned on a visit
while in medical school and I remember him saying that when
alcoholics were autopsied their blood vessels were as clean as a
whistle. Of course, most having died from cirrhosis of the liver,
their livers were shot to Hell. These poor souls illustrate
perfectly the benefit and danger of alcohol consumption and the
importance of the dose.
A recent 12-year study conducted by Harvard researchers has
been getting a lot of media attention. An article in the January
20 issue of Newsweek on the study mentions that, in 1974 (about
the same time my colleague was in medical school), cardiologist
Arthur Klatsky “stumbled across” evidence that those who
imbibed had fewer heart attacks. Coincidentally, after starting
this column, I stumbled across an article by Klatsky in the
February 2003 issue of Scientific American. Klatsky is a senior
consultant in cardiology at the Kaiser Permanente Medical
Center in California and is a graduate of Harvard Medical
School.
The Harvard study followed nearly 40,000 men over the twelve-
year period and found that men who had a drink or two from
three to seven times a week cut their chances of a heart attack by
a third. Klatsky is still studying the problem and last November
he and his colleagues presented the results of a study on 129,934
patients over the period from 1975 to 1998. During that period
over 16,000 died, 3,001 from coronary heart disease (CHD).
Analysis of the data showed that those who had a drink or two a
day were 32% less likely to die from CHD, in remarkable
agreement with the one-third reduction found in the Harvard
study.
In his article, Klatsky stresses a number of points, the most
important being moderation, i.e., one to two drinks a day for
men. A drink is defined as 12 ounces of beer, 5 ounces of wine
or 1.5 ounces of hard spirits such as vodka, gin, scotch or
bourbon. All these drinks contain nearly the same amount of
alcohol. As has been widely reported, moderation for women is
one drink a day and even then there is the tradeoff with an
increased risk of breast cancer. All bets are off if you imbibe
more than those one or two drinks a day, with liver cirrhosis,
certain cancers, high blood pressure, stroke, damaged heart
muscle, suicide and accidents being among the possible
consequences. There are no benefits to overindulgence!
Why does alcohol in moderation have a beneficial effect vis a vis
CHD? Klatsky says the evidence is solid that alcohol increases
the amount of HDL, the “good” cholesterol, by 10-20 percent.
This HDL is thought to help remove and transport the “bad”
LDL cholesterol away from the walls of the blood vessels,
diminishing the chances of plaque buildup. About half the
beneficial effect of moderate alcohol consumption is due to this
increase in HDL.
The other beneficial effect of moderate alcohol intake is an
increased anti-clotting effect. Klatsky cites “moderately
supporting” data that indicates alcohol lowers levels of
fibrinogen, a clotting agent in the blood. The effect is to lessen
the chances of clots forming on artherosclerotic plaques on the
blood vessel walls. There are other possible benefits such as
improved conditioning of the heart muscle and even lessening
the chances for adult-onset diabetes. However, Klatsky doesn’t
consider the data conclusive on these other possible benefits.
We’ve all heard about the “French paradox”, the fact that the
French suffer relatively few CHD cases even though the typical
French diet is loaded with all those cheeses and rich dishes not
thought to promote good heart health. Red wine is the savior; at
least that’s the lore. Klatsky cites some work with his colleagues
on Californians and a Danish study, both of which found that the
red wine drinkers had a significantly lower risk of CHD than
those who drank beer or hard liquor.
But there’s a catch. Klatsky points out that these two studies are
“confounded” by other factors. For example, the Danish diet is
typically loaded with healthful vegetables, fish, salads, olive oil,
etc., while the California wine drinkers were typically better
educated, more temperate, smoked less and overall tended to lead
healthier lifestyles than the beer and liquor drinkers. These
factors make it difficult to come to any firm conclusion that wine
is inherently a better choice than other alcoholic drinks.
Naturally, the biggest danger of taking to heart the drinking
regime is that of overindulgence and alcoholism. Is alcoholism
genetic or is it caused by some environmental factor, notably
stress? The answer is yes. Take the work of Inge Sillaber and
Rainer Spanagel and their colleagues at the Max Planck Institute
of Psychiatry in Munich reported in the May 3, 2002 issue of
Science. They ran studies of the behavior of two kinds of mice
given the chance to choose freely between water and water laced
with between 2 and 8 percent alcohol.
One set of mice was composed of ordinary wild mice, nothing
special. In the other set, the mice were bred with a particular
gene missing. These “knockout” mice were missing a gene
responsible for the release of a hormone related to reacting to
stress. What knocking out this gene did was to blunt the mice’s
response to stress. The knockouts were not as anxious about
things as the normal mice and would eagerly explore places the
wild mice would avoid.
The German workers placed the two sets of mice in their cages
with two bottles, one containing pure water and the other the
alcohol-water mixture. Hopefully, if we were given such a
choice, we would realize the benefit of concentrating on drinking
the water, and only occasionally take a nip or two of the good
stuff. It turns out both sets of mice were similarly inclined and
were classed as moderate drinkers.
Now comes the stress. Male mice were placed in cages with
hostile stranger mice, who didn’t take kindly to the intrusion and
would attack the visiting mice. Then the visitors and strangers
were placed in separate adjoining cages separated only by wire
mesh. This was meant to serve as a continuing source of
intimidation. After the experiment, all the mice continued their
moderate drinking behavior. However, a few weeks later, the
knockout mice began to consume twice as much of the alcoholic
beverage while the normal mice kept to their moderate ways.
Later, both sets of mice were subject to another stressful
situation. For three days in a row, they were placed in water for
five minutes and had to keep swimming without any exit.
The knockouts began to drink even more heavily but not the
normal mice. Even six months later, the knockouts continued
their alcoholic ways. The conclusion, of course, is that the
missing gene is responsible for the knockout’s behavior, leading
to the conclusion that alcoholism can be both genetic and stress-
related. With the recent mapping of the mouse genome, it seems
that we and mice share some 99 percent of our genes in common.
Therefore, the results of these mice experiments could be quite
indicative of our own reactions to alcohol. You can be sure that
research is underway to look for similar genes and effects in
humans.
How often do you say or hear it said that the evening cocktail
helps one to relax? I was somewhat surprised to find that
Klatsky found no evidence that moderate alcohol intake had any
beneficial effect on psychosocial stress. Whatever, I’m sticking
to my one drink a day.
Allen F. Bortrum
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