Monday, January 28, 2013

How much alcohol is optimal? Maybe less than you think

I have been regularly recommending to users of the software HCE () to include a column in their health data reflecting their alcohol consumption. Why? Because I suspect that alcohol consumption is behind many of what we call the “diseases of affluence”.

A while ago I recall watching an interview with a centenarian, a very lucid woman. When asked about her “secret” to live a long life, she said that she added a little bit of whiskey to her coffee every morning. It was something like a tablespoon of whiskey, or about 15 g, which amounted to approximately 6 g of ethanol every single day.

Well, she might have been drinking very close to the optimal amount of alcohol per day for the average person, if the study reviewed in this post is correct.

Studies of the effect of alcohol consumption on health generally show results in terms of averages within fixed ranges of consumption. For example, they will show average mortality risks for people consuming 1, 2, 3 etc. drinks per day. These studies suggest that there is a J-curve relationship between alcohol consumption and health (). That is, drinking a little is better than not drinking; and drinking a lot is worse than drinking a little.

However, using “rough” ranges of 1, 2, 3 etc. drinks per day prevents those studies from getting to a more fine-grained picture of the beneficial effects of alcohol consumption.

Contrary to popular belief, the positive health effects of moderate alcohol consumption have little, if anything, to do with polyphenols such as resveratrol. Resveratrol, once believed to be the fountain of youth, is found in the skin of red grapes.

It is in fact the alcohol content that has positive effects, apparently reducing the incidence of coronary heart disease, diabetes, hypertension, congestive heart failure, stroke, dementia, Raynaud’s phenomenon, and all-cause mortality. Raynaud's phenomenon is associated with poor circulation in the extremities (e.g., toes, fingers), which in some cases can progress to gangrene.

In most studies of the effects of alcohol consumption on health, the J-curves emerge from visual inspection of the plots of averages across ranges of consumption. Rarely you find studies where nonlinear relationships are “discovered” by software tools such as WarpPLS (), with effects being adjusted according.

You do find, however, some studies that fit reasonably justified functions to the data. Di Castelnuovo and colleagues’ study, published in JAMA Internal Medicine in 2006 (), is probably the most widely cited among these studies. This study is a meta-analysis; i.e., a study that builds on various other empirical studies.

I think that the journal in which this study appeared was formerly known as Archives of Internal Medicine, a fairly selective and prestigious journal, even though this did not seem to be reflected in its Wikipedia article at the time of this writing ().

What Di Castelnuovo and colleagues found is interesting. They fitted a bunch of nonlinear functions to the data, all with J-curve shapes. The results suggest a lot of variation in the maximum amount one can drink before mortality becomes higher than not drinking at all; that maximum amount ranges from about 4 to 6 drinks per day.

But there is little variation in one respect. The optimal amount of alcohol is somewhere around 5 and 7 g/d, which translates into about the following every day: half a can of beer, half a glass of wine, or half a “shot” of spirit. This is clearly a common trait of all of the nonlinear functions that they generated. This is illustrated in the figure below, from the article.



As you can seen from the curves above, a little bit of alcohol every day seems to have an acute effect on mortality reduction. And it seems that taking little doses every day is much better than taking the equivalent dose over a larger period of time; for instance, the equivalent per week, taken once a week. This is suggested by other studies as well ().

The curves above do not clearly reflect a couple of problems with alcohol consumption. One is that alcohol seems to be treated by the body as a toxin, which causes some harm and some good at the same time, the good being often ascribed to hormesis (). Someone who is more sensitive to alcohol’s harmful effects, on the liver for example, may not benefit as much from its positive effects.

The curves are averages that pass through points, after which the points are forgotten; even though they are real people.

The other problem with alcohol is that most people who are introduced to it in highly urbanized areas (where most people live) tend to drink it because of its mood-altering effects. This leads to a major danger of addiction and abuse. And drinking a lot of alcohol is much worse than not drinking at all.

Interestingly, in traditional Mediterranean Cultures where wine is consumed regularly, people tend to generally frown upon drunkenness ().

41 comments:

Ugur Gundogmus said...

Great info. Impossible to argue with the data.

I don"t drink every day. Two or three times a week: 2-3 glasses each time. It may not be the optimum alcohol intake, but it seems that it`s better than not drinking.

WilliamS said...

"Impossible to argue with the data."

No, it's not, as the authors of the study say themselves. The data is all observational, interesting perhaps, but with limited ability to establish cause and effect or disentangle the enormous number of possible confounders.

With relative risks this close to one, even controlled trials will have difficulty establishing causality with confidence given all the potential biases and methodological flaws, and they will have to be enormous to do so. That is why trials of things like colonoscopy and mammography, weak interventions at best, require massive numbers of participants and even then don't always convince people who haven't already decided to hear the music.

Chris Masterjohn said...

Hey Ned,

Given the observational nature I'm not sure the data says a whole lot -- I mean, it could be confounded by things so simple as moderate people tend to drink moderate amounts of alcohol -- but the idea is interesting.

One thing that jumps into my mind is the interaction between ethanol and vitamin A. Alcohol dehydrogenase detoxifies alcohol, but also activates vitamin A. Many of the adverse effects of alcohol -- liver damage, maybe kidney stones -- could be attributed to ethanol "hogging" this enzyme so it is not available to activate vitamin A. However, one of the "hormetic" effects of low-dose alcohol could be to upregulate the enzyme so that more enzyme is available to activate vitamin A. Probably there is some optimal amount that keeps the enzyme upregulated but doesn't occupy its behavior so as to crowd out vitamin A from activation.

Chris

George Henderson said...

I read a longevity study a while back on the odds of 70yr olds living to be 90. Drinking alcohol 2-3 times a month was associated with longevity a little more than zero or more than 3x alcohol consumption. But not much. Alcohol consumption was a surprisingly weak predictor of longevity in this group (whereas arthritis was strongly associated with survival - explain that!)

http://www.iumsp.ch/Enseignement/postgradue/medecine/doc/Y_PHS_longevity08.pdf

George Henderson said...

@ Chris, there is a mechanism whereby high alcohol intakes convert retinol to a polar metabolite and impair mitochondrial membrane potential:
http://www.fasebj.org/content/early/2005/04/28/fj.04-2809fje.full.pdf

Chris Masterjohn said...

Thanks George. I guess it is complicated at high ethanol intakes, but it would be interesting to see whether there are positive effects on retinoid metabolism of very low non-zero ethanol intakes.

Chris

Ned Kock said...

Hi Ugur. This is speculation, but on a low-carb diet things may be a bit different. See my comment and link on the French paradox below.

Ned Kock said...

Hi WilliamS. The relative risks are around 20 percent lower at the optimal level of alcohol consumption.

Ned Kock said...

Btw, the samples are reasonably large in some of the sub-studies and the meta-study. The authors didn’t have to resort to pointing out that 1 death per 1,000 is a whopping 50 percent less than 2 deaths per 1,000.

Ned Kock said...

Hi Chris. That could be tested with a simple nonlinear model with the following two links: (alcohol consumption) -> (vitamin A status)  (mortality), and (alcohol consumption) -> (mortality). If the latter link were to be nonsignificant and the former significant with an inverted J-curve shape between (alcohol consumption) -> (vitamin A status), the model would support your point.

Ned Kock said...

The study linked below supports the (alcohol consumption)  (vitamin A status) link, but only the right side of an inverted J-curve relationship.
http://europepmc.org/abstract/MED/6681629

Ned Kock said...

Btw, Chris, I still wonder if alcohol intake may be beneficial because it induces ketosis when people drink after a fast, or because it intensifies ketosis when people drink on a low-carb diet, assuming that ketones may act as antioxidants (remember our brief chat in Boston last year?). This would be consistent with the French paradox:

http://www.sciencedirect.com/science/article/pii/014067369291277F

Angela said...

I wonder how much the centenarian's ethanol consumption was reduced by the fact that she put the whiskey in hot coffee. Surely her longevity has much more to do with other factors (genes, coffee, diet, exercise, sleep, etc).

Ned Kock said...

Hi Angela. I usually mention single cases to show that the opposite hypothesis is not likely – e.g., that is not likely that a bit of alcohol added to coffee would do any harm. Just an additional data point, which in this case helps readers remember the post as well.

George Henderson said...

@ Chris and Ned,
the hormetic vitamin A mechanism is plausible at low and intermittent intakes.
Here are a couple more factors;
when liver cells are damaged by alcohol (or anything else), hepatic stellate cells (Ito cells) become activated - they are important agents in both repair and fibrosis.
HSCs also store the liver's retinol, and release the stores rapidly as they activate.
The retinol helps the undamaged cells to replicate while the activated HSC toddles off to fix the damaged extra-cellular matrix and play its role in the inflammatory response.

Ketone bodies can also trigger the retinol-polar metabolite conversion.
This might fit in with two things - retinol deficiency being so destructive in voluntary starvation scenarios, and polar bear liver being so toxic in arctic survival scenarios.
Removal of retinol by alcohol or ketones might serve some adapative purpose at average levels.
I wonder if alcohol was protective in the CARET study...

Michael Barker said...

When I first became diabetic, the doctors looked for medications that would control it outside of insulin. They, by the way, they never did find anything except insulin. I found that drinking whiskey did the job. I guess through its toxic effect on the liver.

Okay, we already know I'm a weird diabetic.

Anya said...

Alcohol also inhibits the production of glutamine.

It is interesting to note then that phenylbutyrate (used as a novel way in combating certain cancers) also depletes glutamine.

Could reducing intra cellular glutamine (chronic or acute ?) be the source of the longevity ?

Ned Kock said...

Michael! It’s been a long time since you last commented here. A colleague of mine recently developed what seems to be T2KPD. It was quite a scare – like a T1 episode, but with some recovery of beta cell function. I referred him to your site.

David Isaak said...

Hi, Ned-- I agree that alcohol per se has benefits; but I also think that the choice of beverage makes at least some difference.

But it gets rather tangled, because alcoholic beverage choice tends to be tied up with food choices (beer and pizza vs wine and cheese)--as you note in your French paradox remark.

A lot could depend on dietary status. I've read speculations that in Medieval England, beer was probably vital as a source of B vitamins; but if you're not undernourished, then perhaps its benefits decline rapidly. And, as you say, low-carb or fasting status can make a big difference with wine or spirits (beer's too carby to maintain low-carb status).

I'm trespassing on Chris' territory here, but in terms of diet and the slope of those J-curves, I wonder if the point at which alcohol benefits zero out relative to no intake is affected by choline consumption. Choline is liver protective even in cases of substantial ethanol intake.

dearieme said...

My cardiologist asked how much I drank. I said a glass of wine (125 ml) with dinner five or six times a week (with the wine sometimes replaced by beer, cider or whisky, depending on what we are having for dinner).


He said it would be better to drink that amount seven days a week.

dearieme said...

More data that shows no dependence on age, sex, weight.....

Does a glass of wine really have equal effects on the health of a slip of a girl and of a burly, tall, 65 year old male?

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Ivor Goodbody said...

Damn you Ned - I'd given up alcohol years ago and FINALLY trained all friends and relatives into refraining from even offering it to me.

And now this.

You have me seriously reconsidering whether to add a teaspoon or two of booze to my food or cocoa each day.

Two thoughts, one pro, one anti.

1.Could this study on ethanol and worms http://www.ncbi.nlm.nih.gov/pubmed/21871869# point to a possible chemical mechanism for the data you cite, I wonder? A tiny amount of ethanol yields a massive boost to (worm) longevity, it seems.

2. Could the benefit simply be an artifact of alcohol as a social lubricant and therefore marker of better mental health status, with all the well-attested benefits thereof in older adults?

This studyhttp://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2010.01286.x/abstract doesn't quite rule it out, but doesn't conclusively rule it in either:

"Findings are consistent with an interpretation that the survival effect for moderate drinking compared to abstention among older adults reflects 2 processes.

First, the effect of confounding factors associated with alcohol abstention is considerable.

However, even after taking account of traditional and nontraditional covariates, moderate alcohol consumption continued to show a beneficial effect in predicting mortality risk."

My teaspoon is poised over my cocoa in anticipation of your answer.

Wishing you lifelong health

Ivor

Krissie said...

Interesting post about alcohol and longevity. My grandfather always had a beer after work - he lived to be 87, although the last 12 years of his life he suffered from Alzheimer's disease. Wondering if there's any correlation there?

Kim Øyhus said...

Worms also react well to similar amounts of alcohol:

Caenorhabditis elegans Battling Starvation Stress: Low Levels of Ethanol Prolong Lifespan in L1 Larvae

Ivor Goodbody said...

Since my last comment/question, I found this:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1993980/

"Beneficial Effect of Low Ethanol Intake on the Cardiovascular System: Possible Biochemical Mechanisms"

which says this:

"Low ethanol improves insulin resistance, increases high-density lipoprotein and stimulates activity of the antioxidant enzyme, paraoxonase. In conclusion, we suggest that chronic low ethanol intake confers its beneficial effect mainly through its ability to increase antioxidant capacity and lower AGEs."

But also this:

"[D]ue to the addictive nature of alcohol, recommending ethanol intake at any level may not be prudent.

It may be more appropriate to suggest other agents which act in a similar fashion and may provide the same beneficial effects without the complication of addiction.

Supplementation with antioxidants including vitamin C, E, or B6, N-acetylcysteine, lipoic acid and coenzyme Q10 has been shown to lower blood pressure in animal models and humans with essential hypertension...In humans, antioxidants have also shown a beneficial effect on atherosclerotic endpoints in several studies...As well, various anti-AGE therapies, which either prevent or reverse AGE formation, such as pyridoxamine, thiamine, metformin, alagebrium, or soluble RAGE have been shown to attenuate hypertension and atherosclerotic disease."

For detailed refs, see paper

Wishing you lifelong health, Ivor

Ivor Goodbody said...

@David Isaak

The large meta-study referred to here:

http://www.theheart.org/article/1189421.do

showed dramatic risk reduction for CVD, and some but not so much for stroke, with the type of low-moderate ethanol intake Ned discusses, but the article concludes:

"The effects were independent of whether alcohol was consumed in beer, wine, or liquor."

Wishing you lifelong health, Ivor

George Henderson said...

What is the evolutionary explanation for beta-butyrate inducing retinol degradation?

Here it is:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812036/

It is puzzling why metabolic regulation by the pathway described in this report depends on retinol that vertebrates cannot synthesize de novo. In limiting vitamin A to nutritional sources, there must be an evolutionary advantage of such import as to override the physiological needs for vitamin A in vision and retinoic acid-dependent transcription. The answer may lie in the scenario that finite amounts of vitamin A are subject to depletion during periods of severe starvation when an organism is forced to conserve energy. Our observation that in the absence of vitamin A energy generation by respiration adapts downwards appears relevant in this context.

- it makes sense now; it is about how adaption to starvation conserves energy.
Never mind the thyroid. But it might be where low-carb metabolic slowdown comes from.

Anonymous said...

how can not drinking alcohol at all be harmful in any way? what is the evolutionary advantage? or are we trying to justify our little transgressions?

Ivor Goodbody said...

@Anonymous

I don't think that's how the argument runs. It's not so much that teetotalism may be harmful, as that it may possibly deprive us of a benefit conferred by (very) moderate drinking.

The evidence for heart and circulatory benefits seems strong and getting stronger, the risk reduction in mortality from all causes including cancer has been estimated at 13%, but conversely ANY alcohol consumption seems to raise risks for some cancers, especially in women.

To that extent, arguably, we're better off taking in some alcohol than none, especially if we're men.

Wishing you lifelong health

Ivor

Ivor Goodbody said...

In the absence of an opinion from Ned as to whether the benefits of drinking are down to sociability or ethanol, I've gone with the latter and start adding a tablespoon of brandy or whisky to my cocoa each morning.

I'll let you know how it's gone in half a century or so, I hope

Until then, wishing lifelong health to all

Ivor

Ned Kock said...

Hi Ivor. Alcohol as a social “lubricant” makes some sense. The problem is that this happens in the context of the mood-altering effects of alcohol. And, as far as how much alcohol to drink, my guess is that if it affects your mood at all then you had too much to drink.

If one relies on alcohol to make him/her relaxed, he/she is in the path to addiction and abuse, in my opinion. It may be the beginning of a path that will never progress, but arguably it is a slippery beginning.

annlee said...

Dr. Robert Lustig notes the similar effect of fructose on the liver as alcohol. Would fructose - in moderation - be suitably hormetic?

Intervention services said...

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Zorica Vuletic said...
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Zorica Vuletic said...
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Zorica Vuletic said...

Ivor, it is now August.

Do you have any updates on your addition of 1tbsp of brandy or whiskey to your morning cocoa?

I am seriously considering this little experiment for myself. I would put brandy or whiskey (I like those two choices) in my morning coffee. I suppose it would be difficult to tell within a month, since this seems as a long-term effect. But what I can look for in a month's time is if there is an absence of negative health consequences. etc.

I recall a time when I was very put off from alcohol due to who I was living with. I decided to have some 'blue berry' tea, which was brandy, with (not even blueberry) tea. It was a berry flavoured tea of some sort. It was one of the most enjoyable alcoholic beverages I had ever had in my life. It was much nicer than wine, although I do enjoy wine, but always prefer just a half glass, because I feel like a whole glass is just 'too much' (for me).

So here goes: coffee + brandy/whiskey for a month. :)

Zorica Vuletic said...

"Btw, Chris, I still wonder if alcohol intake may be beneficial because it induces ketosis when people drink after a fast, or because it intensifies ketosis when people drink on a low-carb diet, assuming that ketones may act as antioxidants" [French paradox]

"- it makes sense now; it is about how adaption to starvation conserves energy.
Never mind the thyroid. But it might be where low-carb metabolic slowdown comes from."

Based on what I am inferring here, it seems that the (small) amount of alcohol consumption on a daily basis seems to be not just 'not harmful, and so don't worry', but rather might be beneficial for successful LC (to whatever one thinks is LC). ie. It might be that the alcohol would stop a potential 'metabolic slowdown' that some see on LC diets.

Hmmmm....


Insights from Ned, would be greatly appreciated. I do realize this is an older post. I'm reading back on your blog and am thoroughly enjoying it. You have many opinions which I agree with.

Ivor Goodbody said...

Zorica

Sorry to take so long to reply to your August comment. I have only just had reason to review the subject and this thread.

This entertaining review of the benefits of drinking by Doll (the UK epidemiologist who officially linked smoking to lung cancer)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2128014/pdf/9448535.pdf

concludes:

"There is no specific benefit associated with one type
of beverage, but the benefit derives from the content of
ethanol and the extra benefit associated with wine in
some studies can be accounted for by differences in the
pattern of drinking."

That extra benefit is, however, quite large, which suggests to me that if you have an established pattern of healthy drinking (eg you are a Greek shepherd!), you shouldn't upend it in search of some "optimal" result.

But if you are starting from scratch and have the discipline to implement a new regime regularly, pick the most convenient beverage for your way of life.

I would prefer to drink wine at lunch, but as this would mean opening a bottle all to myself and drinking just one-sixth of it per day, while trying to keep the rest fresh all week, it's not practical. Nor does it fit with my work schedule. Nor would it go down well with those whom it is easiest to tell I am teetotal (because if I try to drink with them, they will - annoyingly - continue to fill my glass without asking and when I'm not looking).

So I now put ~1 tablespoon of white rum in my cocoa each morning, first thing. Not brandy or whisky, because

(a) they often contain caramel, a burnt sugar I don't want in my diet
(b) they're more expensive

Wishing you enduring health

Ivor

IvorGoodbody said...

Ned

A study just appeared which suggests that drinking alcohol up to or more than 2.5x per week increases stroke risk up to threefold, "independent of total AMOUNT of alcohol consumption" [my emphasis].

http://onlinelibrary.wiley.com/doi/10.1111/ane.12243/abstract

This seems at odds with your view that "the optimal amount of alcohol is somewhere around 5 and 7 g/d, which translates into about the following EVERY DAY" [my emphasis].

As a daily drinker of your recommended amount, I would love to hear your take on this new research (not that I blame you for putting me up to it, you understand! I am the sole author of my own (mis)fortunes, within the constraints of circumstance.)

Wishing you enduring health

Ivor Goodbody

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