Acetylcysteine does not prevent hangover, study shows (update)

N-Acetyl-L-Cysteine (NAC)-containing supplements are widely propagated for hangover prevention, although there’s been no scientific evidence backing this claims. First-ever results from a placebo-controlled hangover trial now became available.

The popular supplements are useless. NAC does not prevent hangover.

This blog has written extensively in finnish about a scam product by Rohtos Labs from Oulu. Called SUOJA – formerly Detoxformula -, it contains NAC as main ingredience, and was sold internationally.

 

What trial?

The world’s first-ever placebo-controlled trial of NAC in hangover prevention was conducted already in August – December 2015 in Pennsylvania, US. Run by the St. Luke’s Hospital and Health Network, it enrolled 62 people and used a crossover design.

49 participants had analysable data. They were randomized in groups of 23 and 26. 2/3 were male, race was not recorded. Alcoholism was an exclusion criterium. Outcome measure was the Hangover Symptoms Scale (HSS), which has 13 items á 4 pts max. The worst (but unimaginable) hangover thus would score 52 pts.

Participants drank beer until reaching a blood alcohol concentration of 0.1. The number of drinks was recorded, and NAC 600mg capsules were given, 1 caps for 3 drinks. The next morning, participants filled out the HSS questionnaire.

The results should make NAC sellers and users feel uncomfortable: NAC and placebo had exactly the same effect. The HSS scores were 0-35 and 0-38, respectively. That means, that hangover really occured and the alcohol dose was sufficient – as should have been the NAC dose.

Still worse, NAC had significantly more side effects than placebo. In the Acetylcysteine group, 22% of users experienced adverse effects, while in the placebo group adverse reactions were registered in only 8%.

These results became available a few days ago through the Study results-tab of the trial’s registry entry at clinicaltrials.gov. Ahead or in place of a peer-reviewed publication, they went completely unnoticed by the supplements community.

This demonstrates again, how dietary supplements are used without justification, based only on lab studies. Rarely such useless and potentially hazardous “biohacks” get so cleanly refuted as in this case.

***UPDATE 9.7.2018***

The second, bigger NAC study with 200 participants was now terminated early. Obviously it was deemed futile to try to demonstrate a non-existent effect.

NCT03104959

15 thoughts on “Acetylcysteine does not prevent hangover, study shows (update)

  1. I have used nac for hangover prevention and I suggest it is 60-70 % effective in my experience. That the trial mentioned herein is flawed in that participants are administered the supplement after they have consumed all the alcohol. At the end of the evening. That the literature which accompanies NAC for hangover prevention states it should be taken an hour in advance of and then every hour or so, during an evening of drinking. Takne inthis manner, you are essentially absorbing nac, throughout the night, to help it build those antioxidants on the fly. That taking it after drinking is too late, as all the damage from acetylaldehyde has already been done. Hence the negative trial results. Well, that’s my anecdotal 2 bits. I have used it, and with decent success.

    1. It’s a common feature of alternative treatments, wonder supplements and other “biohacks”, that failures are blamed on the user. “Would you’ve taken it before, it would have worked!” – “Didn’t you know it can not be taken together with X?” and so on.

      There is no credible “literature” to accompany any NAC product for hangover prevention. Simply because it’s not scientifically tested. The only thing we have in humans is this single study, and it’s negative. I could go on with a tractate about GI physiology to show you got the wrong idea how these substances “work”. But that would be nothing more than another rant w/o relevance for the question.

      If someone has a link to reliable information, please put it here for discussion. So far most does come from people with a commercial interest, not from scientific research.

  2. In my opinion the study you have linked is more ore less worthless because it has too less participiants and is using only a Median Value for the score. At least total Hangover symptom score is 10 vs 13 and nauseated score is 0 vs 1 for NAC vs Placebo. Though its insignificant the NAC users had a little less hangover than placebo users.

    Second is what Tony said. You should take it before drinking, at least for mice it had a negative effect taking NAC after drinking. (liver damage wise)
    https://www.ncbi.nlm.nih.gov/pubmed/16439183

    Third, I am getting an alcohol flush reaction when drinking alcohol and for me it is greatly reduced by taking NAC. Most probaly NAC safes a little from Acetataldehyde intoxication.

    I am not really saing it will help against hangover for most of the people but it can have other positive effects and for people like me who gets an alcohol flush reaction the hangover is probaly reduced greatly.

    1. The study had enough power to detect meaningful differences.

      The side effects difference had trend-level significance (p=0,09 roughly calculated). If there had been a few more participants (1-2 more), it would have reached significance.

      For power calculation, see for example the good tutorial in Critical Care, which is already a classic and should be understood before claiming anything about “too small” studies. Other literature about biostatistics will tell the same (but is harder to read, in my opinion).

  3. This study is complete nonsense. Participants were given NAC at the end of the night, after drinking. Of course it’s not going to prevent a hangover if administered after a night of heavy drinking. I use NAC regularly, and it must be taken 30 minutes to an hour prior to drinking, with pills taken throughout the night with each drink. It works wonderfully if taken properly… I’d say about 70-80 percent reduction in hangover symptoms a night after heavy drinking. This study is ridiculous.

  4. I have zero commercial interest in NAC, but I do have an interest in my ability to wake up without a hangover in the morning, and my results, as indicated were reasonably worth while. Prior to taking NAC, I’d consistently wake up hungover after a night of drinking. As I got older, I could tolerate even less alcohol. Taking NAC had immediate effect for me.

    Anyway, I already admitted my results were around 70% effective, and agree they are purely anecdotal, but for you to suggest I am somehow doing it for “commercial interest”, or that I am somehow not credible, is plainly false. It worked for me. My experience is very credible. More credible than the trial I just read which was- by and large- a waste of time in the manner it was conducted, as well as your own “unfounded opinion”.

    I was interested to read the trial results, but the manner in which the trial was done rendered it usesess. Gastrointestinal physiologies notwithstanding.

    1. I didn’t mean you with that. To expect that such a comment would be in commercial interest, would be silly, as this blog is too unimportant…and I plainly hate discussions where others are un(dis)provably blamed for sinister agendas.

      Apologies if that was misunderstandable.

      1. Ha – my apologies in return.

        As soon as I submitted my response, I read your reply more fully and felt my reply might have been deemed a little defensive, so sorry about that.

        I still stand my my personal experience using NAC.

        Have honeslty been trying to find supporting literature for my experience which, as you indicated, does not exist, so was just a little disappointed at how they arrived at their conclusions. The trial meant little to me.

        I have also read literature that they adminster NAC for tylenol overdose, so it must have some antioxidant / liver benefit. I am sure there is also literature indicating its benefit in improving liver function, so really a harmless supplement to take if you are planning to drink alcohol.

  5. NAC definitely improves hangovers (not perfect but vast improvement) but it must be taken in advance. Again no commercial interest.

    1. Again: That was not aimed at commenters.

      If there is any reliable source for the claim that it works if taken *before*, please let me know. Otherwise it’s irrelevant for our question, because this post is about science and not personal views.

  6. In the absence of high-quality evidence I’m not going to pretend to know NAC definitely works and I haven’t tried it myself. But every anecdotal account of using NAC to prevent hangovers on the internet speaks of taking the supplement BEFORE and often during and after drinking. If it is indeed true that in this study they had participants take NAC after finishing drinking then their null result doesn’t prove anything. Mechanistically we should EXPECT a null result because much if not most of the alcohol should’ve already been converted to acetaldehyde, and, indeed much of the acetaldehyde may already have been converted to acetic acid.

    1. You’re right about the evidence-based view. It’s often forgotten that the best available evidence has to be used. If there are no good studies, anecdotal evidence is the best we have and must be used. I have to keep that in mind.

      On the other hand, the question here was not before or after. That’s beyond scope and would require comparative studies.

      I’m afraid there will be no further studies on NAC for alcohol soon, because the best we have (one with NAC taken after drinking) was negative and there’s no great interest in that topic from the industry. The pharmaceutical industry, which usually sponsors bigger RCTs, not the supplement industry which usually relies on prejudice and half-truths.

  7. If the subjects only drank to a blood alcohol content of .1%, I don’t expect there would be much hangover, and the test would not be very sensitive. And looking at the study results, there was very little reported hangover symptoms in either group. All of the 1-4 symptom ratings were only 1 for both groups, except for nausia, which was 0 in the NAC group.

    In my personal experience, NAC does work, specifically when the alcohol amount is enough to be considered very drunk.

    This article draw too positive and unreserved a conclusion from a single, seemingly flawed study.

  8. The study does, though, seem to show that nausea is less in the NAC group, while other effects are equal. I ask you, could it be that there is more than one process at work in a hangover? Consider the way NAC is used by hospitals to treat certain overdoses, and it’s method of action.

    Could it be that nausea symptom is caused by the buildup of toxins in the brain, which NAC combats by increasing glutathione, while the dehydration symptom is caused by another process that NAC does not address, namely the production of vasopressin?

    The article does not contemplate this. I use NAC specifically for the nausea prevention and do not expect it to prevent dehydration.

    The update section in particular seems un-objective when it states that the reason for a new study’s discontinuation is “obvious” when actually the reason is not obvious to us. The writer seems to have an axe to grind.

    1. That makes sense to me! I still feel some effects of a hangover (tiredness, soreness etc.), but the worst symptomd—the nausea and lack of appetite (and to some extent, the post-alcohol anxiety)—are pretty much nonexistent. I was almost blackout drunk this Saturday, yet shockingly functional yesterday (it’s Monday now). I slept at my friend’s place, and he’s STILL feeling the after effects today…
      Actually, the last time I had a proper hangover was before I started taking NAC (and mind you, it was so bad that I couldn’t sleep and started experiencing panic attacks, trembled and felt horribly weak, had to take an ice cold shower because I felt feverish, was hardly able to swallow food, and almost vomited several times), and I’ve been on several binges since then.
      I originally started taking high doses of NAC to see if it would help me with my skin picking disorder and trichotillomania (it has somewhat alleviated my body-focused repetitive disorders thus far). So finding out that it can prevent hangovers if taken about 30+ minutes beforehand was a nice surprise! After researching it, I do avoid taking any after I have started drinking, and about 16-24 hours afterwards, since apparently it can have the opposite effect of making ethanol more toxic for your body if used too soon after drinking.

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