Alcohol on keto

This article isn’t about alcohol tolerance.  It’s about your liver.

Tl;dr: with a basic knowledge about alcohol metabolism and ketoadaptation, drinking on keto gives me pause.

It might be nothing, but it gives me pause.

Alcohol is metabolized primarily by alcohol dehydrogenase, producing acetaldehyde and reducing equivalents as NADH.  This pathway produces energy.

Some alcoholics are skinny, in part, because of the other pathway: CYP2E1 (MEOS).  CYP2E1 actually consumes energy to metabolize alcohol (it’s like “negative calories” in this #context).  Recall this blog post, where it was shown that chronic alcoholics would gain weight if extra calories were given in the form of chocolate but not alcohol.  It’s because alcoholism enhances CYP2E1.  Downside is that CYP2E1 produces superoxide and lipid peroxides which contribute to inflammation, fibrosis, and eventually liver failure (eg, Porubsky et al., 2008).


CYP2E1 lipid peroxidation


An old rule of thumb is that it takes about 15 years of heavy drinking in an otherwise healthy person to induce liver failure.  That seems way too specific, imo, but whatever.





What else increases CYP2E1?

-Fasting (eg, Johansson et al., 1988).  Drunkorexia, or fasting prior to drinking to offset the alcohol calories.  This also applies to intermittent fasting.  You can offset the calories by fasting, but increased CYP2E1 makes this practice particularly nefarious.

-Ketogenic diet.  There are no studies on alcohol ingestion in people following a ketogenic diet, but given the known impact of CYP2E1 on liver pathology, this way of eating might take that theoretical 15 years down to 10.  Or something.  Guessing here, but I don’t think drinking on keto is healthier than drinking on LC/Paleo/whatever other diet… probably the opposite.  Maybe it’s a matter of goal posts.



CYP2E1 has a function, and it produces oxidative stress with substrates other than alcohol… that is, even if your not imbibing, CYP2E1 still works if it’s upregulated by other factors (eg, ketogenic diet, intermittent fasting)… so might not want to add more fuel to the fire by adding an additional CYP2E1 enhancer and substrate (ie, alcohol).

#context and further considerations:

1) most people following a ketogenic diet are health-conscious, so a few drinks now and then are probably fine.

2) keto is a therapeutic intervention.  If you’re in a state where such an intervention is required, should you really be drinking anyway?

3) there are no direct studies on this.  Like I said, “it gives me pause.”  I have no idea the extent to which this might apply.



THAT SAID, if you still choose to imbibe, it may be prudent to consider these… considerations

-Long and medium chain saturated fats: swap out some of your other cooking fats for cocoa butter and coconut oilThese are strongly protective against alcohol-induced liver damage, possibly due to their intrinsic molestation-resistance.

I’m not suggesting dumping all your butter and olive oil, just swap out some.

-Coffee.  Yay!  There are many epidemiological & mechanistic studies showing a hepatoprotective effective of coffee & coffee polyphenols, and even some specifically in models of alcohol toxicity … sorry, yes, alcohol is still pretty much justifiably classified as a toxin… yeah yeah yeah dose makes the poison, but still.

-Asparagus, Brussels sprouts, broccoli, artichokes, and a variety of LC plants* to bolster endogenous antioxidants.  Also, some supps like NAC, silymarin, and maybe TUDCA might be helpful here, too.

*LC plants: I specify LC in this context because high carbs + alcohol = no bueno. In her excellent book “Lights Out!,” T.S. Wiley frequently groups alcohol together with carbs.  I concur.

Just some food for thought.

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  • Tuck

    I’ve come across some interesting links on this same topic. It turns out that omega-6 fats are required to induce alcoholic liver injury (to your observation about eating healthier fats):

    “Dietary linoleic acid is required for development of experimentally induced alcoholic liver injury.”

    It turns out that not only are the toxic omega-6 metabolites degraded by alcohol dehydrogenase (ADH):

    “The hepatocellular metabolism of 4-hydroxynonenal by alcohol dehydrogenase, aldehyde dehydrogenase, and glutathione S-transferase.”

    But they also break down ADH:
    “4-Hydroxynonenal regulates 26S proteasomal degradation of alcohol dehydrogenase.”

    So what I suspect is happening is that ethanol and 4-HNE are both competing for a limited amount of ADH, and that 4-HNE is breaking down ADH, resulting in the damage to the liver when the two are combined. Since the liver damage also occurs w/out ethanol (non-alchoholic fatty liver disease is induced by a high omega-6 diet, and resolved on a low omega-6 diet), I think it’s safe to say that the primary problem isn’t with the ethanol, keto diet or no. 4-HNE and the other omega-6 metabolites are causing the liver damage, and alcohol is contributing to it by reducing the available amount of ADH.

    See here:

    “These results indicate that proteasomal activity was not directly affected by ethanol or CYP2E1 induction. Since 4-hydroxynonenal (4-HNE) concentration was significantly increased at 1 month of ethanol feeding, it was suspected that 4-HNE adduct formation with proteasome subunits could be the mechanism of proteasome inhibition.”

    “The effect of ethanol-induced CYP2E1 on proteasome activity: the role of 4-hydroxynonenal”

    This is not license to be a lush, of course, but I think it does a pretty good job of explaining what’s going on…

  • TechnoTriticale

    re: #context and further considerations:

    4) If you are Apo E4…

  • George

    Why wouldn’t butter have the liver-protecting effects of its SFA and MCFAs? Tallow and even EVOO do well in animal models of alcoholic liver disease, though EVOO is just one study, tallow is heaps.

    • “I’m not suggesting dumping all your butter and olive oil, just swap out some.”

      I didn’t say butter was harmful, just that “swapping out some” drastically increases the SFA/UFA ratio

      • George

        Sure, I think adding coconut oil is a good idea as that seems to be a star. But my reading of the evidence is that about 80% of the protective effect comes from keeping PUFA low, 20% from specific effects of various SFAs, and MUFA is not a problem.
        However I looked up the EVOO reference in Kirpich et al 2016, and this study only compared 5% EVOO with chow. So it may be at higher intakes there is too much PUFA, as PUFA in EVOO is equivalent to lard, which isn’t good.

        However, CO, tallow, cocoa butter in these experiments is always cut with a little corn oil to replace PUFAs lost to MEOS. This takes it to 5% PUFA in fat at 35%E fat and this is the protective formula. So this does allow the 50/50 olive/butter mix at a 35%E fat diet, but you might want to swap out some of the EVOO at higher fat intakes.

  • George

    MEOS enzymes are also PUFA oxidising enzymes – there was probably no ethanol in the sea, so these proteins evolved to create and degrade eicosanoids; see here for the overlap between alcohol and PUFA metabolism, which explains NAFLD.

  • mikemarkham

    I’ve been keto for over five years and drink on the weekends, typically 12-15 drinks total. I get physical exams every year and my low-grade inflammatory markers are barely registered (hs-CRP). Does this debunk the inflammation -> liver failure postulation as it relates to alcohol ingestion on keto?

    • unfortunately not, but maybe if you had low plasma LPS & liver enzymes and followed a relatively low SFA diet

    • nero88888

      Someone should put a bullet between your eyes

  • John Smith

    Kinda disappointed Ash Simmonds hasn’t commented on this yet.

  • Scott Stevens

    My dad has been a consistent heavy/dependent drinker for 50 years yet a liver test showed no signs of damage. He’s also a heavy coffee drinker. He drinks 5 cups a day (freshly ground good quality) and his servings are double what I would have. I’m sure the coffee has protected his liver, there’s no other explanation.