On 2015 Feb 27, David Keller commented:

Proposed techniques to preserve blinding in a randomized trial of ethanol capsules versus water

In reply to my letter [1], Dr. Huang writes: "We agree that a large prospective randomized controlled trial will be the most valuable path to evaluate the effects of alcohol on all-cause mortality and cardiovascular health."[2] I agree; there is voluminous epidemiological and observational evidence that mild to moderate ingestion of ethanol has benefits on cardiovascular and all-cause mortality in various populations. What we need now is a randomized interventional trial to confirm and quantify the benefits and the risks of low-dose ethanol, so that physicians can prescribe ethanol to appropriate patients with confidence.

The design of such a trial will be crucial. Dr. Huang wrote: "we are skeptical concerning the use of ethanol capsules. The blindness of the study design would not be guaranteed because the patients in the treatment arm may experience psychotic, cutaneous, or other effects."

I request clarification: what does Dr. Huang mean by "psychotic" effects? Psychosis is described among heavy abusers of ethanol, in both the intoxicated and the withdrawal states. However, the ingestion of mild to moderate doses of ethanol does not normally cause any form of psychosis or of hallucinations. Patients with any history of ethanol abuse would be excluded from a randomized trial.

Unpleasant cutaneous flushing is caused when persons with a genetic deficiency of alcohol dehydrogenase, or a mutated allele of this gene, ingest even small amounts of ethanol.[3] This reaction generally causes these persons to avoid ethanol ingestion, and they should be excluded from a randomized trial.

If there are no other objections to a randomized trial of ethanol, then I would like to propose a toast to its safe and successful completion. Cheers!

References

[1] Keller DL. Ethanol should be subjected to a randomized controlled trial. Mayo Clin Proc. 2015 Jan;90(1):160. doi: 10.1016/j.mayocp.2014.10.013. PubMed PMID:25572202.

[2] Huang C, He QQ. In reply—Ethanol should be subjected to a randomized controlled trial. Mayo Clin Proc. 2015 Jan;90(1):161. doi: 10.1016/j.mayocp.2014.10.012. PubMed PMID: 25572204.

[3] Holmes MV, et al.; InterAct Consortium. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2014 Jul 10;349:g4164. doi: 10.1136/bmj.g4164. PubMed PMID: 25011450; PubMed Central PMCID: PMC4091648.

On 2015 Feb 27, David Keller commented:

Proposed techniques to preserve blinding in a randomized trial of ethanol capsules versus water

In reply to my letter [1], Dr. Huang writes: "We agree that a large prospective randomized controlled trial will be the most valuable path to evaluate the effects of alcohol on all-cause mortality and cardiovascular health."[2] I agree; there is voluminous epidemiological and observational evidence that mild to moderate ingestion of ethanol has benefits on cardiovascular and all-cause mortality in various populations. What we need now is a randomized interventional trial to confirm and quantify the benefits and the risks of low-dose ethanol, so that physicians can prescribe ethanol to appropriate patients with confidence.

The design of such a trial will be crucial. Dr. Huang wrote: "we are skeptical concerning the use of ethanol capsules. The blindness of the study design would not be guaranteed because the patients in the treatment arm may experience psychotic, cutaneous, or other effects."

I request clarification: what does Dr. Huang mean by "psychotic" effects? Psychosis is described among heavy abusers of ethanol, in both the intoxicated and the withdrawal states. However, the ingestion of mild to moderate doses of ethanol does not normally cause any form of psychosis or of hallucinations. Patients with any history of ethanol abuse would be excluded from a randomized trial.

Unpleasant cutaneous flushing is caused when persons with a genetic deficiency of alcohol dehydrogenase, or a mutated allele of this gene, ingest even small amounts of ethanol.[3] This reaction generally causes these persons to avoid ethanol ingestion, and they should be excluded from a randomized trial.

If there are no other objections to a randomized trial of ethanol, then I would like to propose a toast to its safe and successful completion. Cheers!

References

[1] Keller DL. Ethanol should be subjected to a randomized controlled trial. Mayo Clin Proc. 2015 Jan;90(1):160. doi: 10.1016/j.mayocp.2014.10.013. PubMed PMID:25572202.

[2] Huang C, He QQ. In reply—Ethanol should be subjected to a randomized controlled trial. Mayo Clin Proc. 2015 Jan;90(1):161. doi: 10.1016/j.mayocp.2014.10.012. PubMed PMID: 25572204.

[3] Holmes MV, et al.; InterAct Consortium. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2014 Jul 10;349:g4164. doi: 10.1136/bmj.g4164. PubMed PMID: 25011450; PubMed Central PMCID: PMC4091648.