Sunday, April 24, 2011

Alcohol consumption, gender, and type 2 diabetes: Strange … but true

Let me start this post with a warning about spirits (hard liquor). Taken on an empty stomach, they cause an acute suppression of liver glycogenesis. In other words, your liver becomes acutely insulin resistant for a while. How long? It depends on how much you drink; possibly as long as a few hours. So it is not a very good idea to consume them immediately before eating carbohydrate-rich foods, natural or not, or as part of sweet drinks. You may end up with near diabetic blood sugar levels, even if your liver is insulin sensitive under normal circumstances.

The other day I was thinking about this, and the title of this article caught my attention: Alcohol Consumption and the Risk of Type 2 Diabetes Mellitus. This article is available here in full text. In it, Kao and colleagues show us a very interesting table (Table 4), relating alcohol consumption in men and women with incidence of type 2 diabetes. I charted the data from Model 3 in that table, and here is what I got:

I used the data from Model 3 because it adjusted for a lot of things: age, race, education, family history of diabetes, body mass index, waist/hip ratio, physical activity, total energy intake, smoking history, history of hypertension, fasting serum insulin, and fasting serum glucose. Whoa! As you can see, Model 3 even adjusted for preexisting insulin resistance and impaired glucose metabolism.

So, according to the charts, the more women drink, the lower is the risk of developing type 2 diabetes, even if they drink more than 21 drinks per week. For men, the sweet spot is 7-14 drinks per week; after 21 drinks per week the risk goes up significantly.

A drink is defined as: a 4-ounce glass of wine, a 12-ounce bottle or can of beer, or a 1.5-ounce shot of hard liquor. The amounts of ethanol vary, with more in hard liquor: 4 ounces of wine = 10.8 g of ethanol, 12 ounces of beer = 13.2 g of ethanol, and 1.5 ounces of spirits = 15.1 g of ethanol.

Initially I thought that these results were due to measurement error, particularly because the study relies on questionnaires. But I did some digging and checking, and now think they are not. In fact, there are plausible explanations for them. Here is what I think, and it has to do with a fundamental difference between men and women – sex hormones.

In men, alcohol consumption, particularly in large quantities, suppresses testosterone production. And testosterone levels are inversely associated with diabetes in men. Heavy alcohol consumption also increases estrogen production in men, which is not good news either.

In women, alcohol consumption, particularly in large quantities, increases estrogen production. And estrogen levels are (you guessed it) inversely associated with diabetes in women. Unnatural suppression of testosterone levels in women is not good either, as this hormone also plays important roles in women; e.g., it influences mood and bone density.

What if we were to disregard the possible negative health effects of suppressing testosterone production in women; should women start downing 21 drinks or more per week? The answer is “no”, because alcohol consumption, particularly in large quantities, increases the risk of breast cancer in women. So, for women, alcohol consumption in moderation may also provide overall health benefits, as it does for men; but for different reasons.


John said...

Hi Ned,

Regarding your warning about spirits: alcohol seems to cause high liver concentrations of NADH, which in turn would inhibit gluconeogenesis, causing hypoglycemia [1]. So it appears that the insulin resistance would be compensated for, in a twisted way. My guess is that the hypoglycemia is part of the explanation of the "spacey" feeling due to alcohol.

It seems to make sense that if alcohol in women increases estrogen, their risk for type 2 diabetes goes down. It turns out that estrogen increases choline via PEMT [2,3], which is required to export fat (e.g., due to alcohol) out of the liver [4]. Higher choline due to estrogen, would mean lower risk of fatty liver (= an insulin resistant liver).


[1] Berg J.M., Tymoczko J.L., Stryer L. Biochemistry. 5th edition.
Section 30.5 Ethanol Alters Energy Metabolism in the Liver.
[2] Fischer L.M. et al. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 2010 Nov;92(5):1113-9.
[3] Resseguie M.E. Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. J Biol Chem. 2011 Jan 14;286(2):1649-58.
[4] Masterjohn C. Nonalcoholic Fatty Liver Disease.

Ned Kock said...
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Ned Kock said...

Hi John. Very interesting.

Alcohol consumption also induces ketosis, which I believe is one of the reasons behind its health-promoting effects, when consumed in moderation.

There is some evidence that ketones are powerful antioxidants, and I’m planning on blogging about it in the future.

In other words: not hormesis, but plain ole ketones.

Nick said...
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Nick said...

Hi Ned,

John's comment is true in my case. Three years ago I started measuring my blood sugar due to elevated FBS. I found that my postprandial numbers were going above 140 after certain foods, so I reduced my carb intake. I began to feel much better, but noticed that drinking on an empty stomach made me feel 'drunk' after just a few ounces of wine. I decided to measure my BS after wine on an empty stomach and it was dropping into the 50-60s range. An OGTT also showed my BS drop into the 50s at the end of the test.

I always eat food now when I drink alcohol now, but I worry, because my definition of a glass of wine is 6oz. Their 21 is my 28. Real world glasses of wine seem to be 6oz, so if one drinks two 6oz glasses of wine a day, they are at the 21 'limit'.

BTW, it seems that alcohol preceding anything soaked in vegetable oil would be a deadly combination for the reasons pointed out in your post.

John said...

Hi Ned,

I think people draw the hormesis card too quickly once they know the concept. So when they find that a toxic substance has a positive effect, hormesis is assumed almost by default. I think it is better as a backup option, if no other explanation can be found.
Alcohol induced ketosis as an explanation for some positive effects is certainly something that crossed my mind. I'm looking forward to your post.

My personal guess is that something similar applies to apple cider vinegar. It seems to be presented as this magical potion. But perhaps there is nothing magical at all: just water + ketones.


Helen said...


You have an eerie way of posting about things that I have just in the previous day or two started to think or Google about.

I have mild diabetes and was wondering about this. I was never partial to alcohol. Not against it - just not my drug of choice. (That would be caffeine, or, if it weren't so addictive, Ativan, but I steer clear of that.)

But I noticed recently after a half glass of wine (being a near-non-drinker, I am a cheap date) nicer glucose readings that evening and the next morning and am trying to add it to my routine.

I am still trying to sort out the story on caffeine. There are several epidemiological studies showing coffee and/or tea and/or caffeine consumption to be inversely associated with the development of diabetes, even among people with prediabetes, but in diabetics *and* in nondiabetics, it impairs glucose tolerance (increased post-prandial readings), so I am thoroughly confused.

I tried to cut out my 1-2 cups a day, but found life unbearable, so I'm back to 1 cup a day.

Anyway, thanks for the relevant post!

Ned Kock said...

Hi Nick. Another advantage of drinking wine with food is that tooth erosion is minimized.

Ned Kock said...

Hi John. Yes, the hormesis explanation is invoked way too often, and it is hard to falsify.

On your comment regarding vinegar, do you mean to say that food that contains ketones will lead to an increase in blood concentration of ketones?

Usually a fatty meal will increase blood ketone concentrations because of the body’s switch to fat as a source of fuel, and ketones are a byproduct of fat metabolism. The same seems to be the case with alcohol.

Ned Kock said...

Hi Helen, thanks. The topic of coffee and diabetes is rather controversial, and the results of different studies tend to be contradictory:

Frequent contradictory results are a telltale sign that there may be no significant direct effect, and that the effects that are sometimes observed are indirect (due to other variables, which can act as amplifiers).

Btw, I’ve switched from coffee to green tea because I often fast in the morning and like to drink something. Coffee by itself was giving me an unpleasant feeling in the hours after drinking.

You got to listen to your body.

David Isaak said...

Under 21 drinks a week? Not a very challenging limit. (Guys who drink might want to up their intake of cruciferous vegetables--diindolylmethane seems to be an aromatase inhibitor that keeps testosterone from being converted to estrogen-related compounds.)

I didn't know about alcohol speeding ketosis, but it matches with my experience. I can't resist dietary experiments, so I once tried a few days of the Atkins "Fat Fast", where calories come 90% from fat. On one of those days, I had a social event where downing a couple of glasses of cabernet was nigh unto mandatory (not that I was fighting it), and even though I was careful tokeep my water intake up, it seemed to accelerate fat loss greatly.

At other times I've noticed that alcohol seemed to up my rate of weight loss--but only when consumed after a number of days of abstinence. I used to try to explain this with hydration levels, but your post makes me think something else is going on.

Ned Kock said...

Hi David. Alcohol consumption is sometimes associated with weight loss due to malnutrition, this usually happening in alcohol abuse cases. Otherwise it is associated with weight gain.

Alcohol is oxidized with high priority. If consumed together with fat, the fat will be stored and the alcohol will be oxidized for energy, yielding about 7 calories per gram.

Ketones are a byproduct of alcohol oxidation.

David Isaak said...

Hi, Ned--

Alcohol is "associated" with weight gain? I have a little trouble with that statement unless it is highly qualified. If you look at, say, obesity rates in developed countries I think you'd find the association is rather poor and often inverse.

Is it associated with weight gain independent of caloric intake and independent of macronutrient composition?

In any case, I was wondering about the effects alcohol has in accelerating ketosis, not general epidemiology.

It has been my experience that if used in moderate dosage and not used chronically, on a few occasions it has sped weight loss for me, and I'm curious about possible mechanisms. Of course, this is an anecdotal, n=1 observation, but the plural of anecdote is data.

Ned Kock said...
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salvinder said...
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salvinder said...
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Ned Kock said...

Nonsensical spam above (2 comments) deleted.

Ned Kock said...

Hi David. The association between alcohol consumption and body fat gain that I alluded to is definitely mediated by increased caloric intake. Alcohol is a very calorie-dense “nutrient”. It does not become fat itself, but it is prioritized for oxidation. And many people overeat after they have a few drinks.

As for your experience of losing body fat by drinking alcohol, I have a couple of ideas, but they are speculative.

One is that alcohol may suppress appetite in some people, and you may be one of them, exactly because alcohol is oxidized right after it is consumed. While some feel relaxed and eat more, others may feel full of energy and not very hungry.

The other is what I would call “ketosis inertia”. When you consume a nutrient that induces ketosis, the body may stay in that state of ketosis for longer than it would normally be, even after the nutrient is completely oxidized. That is, once in ketosis, the body may stay in ketosis until something that raises insulin levels is eaten.

David Isaak said...

I think the "ketosis inertia" you're referring to is probably part of the answer, and it's a great term.

In fact, I think as with inertia in physics, it cuts both ways: many people find it hard to get full-on ketosis rolling at first. (That, of course, is the principle of the "fat fast"--sudden caloric restriction and little in the diet but fat.)

Alcohol doesn't seem to affect my appetite much one way or the other, but it does tend to make me hot and slightly energized. Maybe in some people the body speeds elimination of ethanol by upping metabolism and NEAT?

"Ketosis inertia." A useful concept!

Ned Kock said...

This idea of ketosis inertia could explain why some people report body fat loss by consuming coconut oil; something like half a tablespoon early in the morning, with nothing else until lunch time.

The fat acid chains that make up coconut oil are absorbed directly into the portal vein via the intestine; they are not packaged into chylomicrons. In part because of that, they cause a quick and significant elevation of ketone levels in the blood.

Possibly the body stays in that ketosis state until lunch time; and ketosis is a relatively “wasteful” state. For most people, simply fasting from evening till lunch time will not put them in deep ketosis. If ketosis continues, it will have to rely on body fat, as half a tablespoon of coconut oil yields about 63 calories, which is less than what most people will burn in one hour.

I say “wasteful” within quotes above because I believe that ketones have other functions – e.g., they may act as powerful neutralizers of free radicals (in other words, as antioxidants).

John said...

Hi Ned,

My vinegar idea was triggered by a discussion on Hyperlipid. Peter quoted a blog post about vinegar's ketogenic potential, see
Personally I don't see why dietary ketones wouldn't raise blood levels: they are water soluble and should be able to easily enter the body. They just don't provide a sustained stream of ketones like the liver does (unless you continuously sip on vinegar).


Ned Kock said...

Makes sense John.

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