Wednesday, 10 May 2017

Disulfiram and alcohols

I was thinking about disulfiram and alcohols - does it interacts with ethanol and methanol only? What about sorbitol, mannitol etc? Should all "-ols" be avoided in diet?
Mainly what about perillyl alcohol - it is monoterpene but does it have something in common with alcohol?
Can you take them simultanesly- disulfiram and perillyl alcohol (solution with NaCl only)? What are your thoughts and experiences?


  1. The question here is whether any given alcohol requires aldehyde dehydrogenase in its transformation and clearance by the body. Disulfiram, as an aldehyde dehydrogenase inhibitor, interrupts the conversion of acetaldehyde (which is itself converted from ethanol by alcohol dehydrogenase) to harmless acetic acid, causing an accumulation of toxic acetaldehyde.

    Likewise, perillyl alcohol gets converted to perillaldehyde. Aldehyde dehydrogenase then converts perillaldehyde to perillic acid.

    This leads to questions such as: is perillaldehyde toxic to humans, and is perillic acid an active cancer-inhibiting metabolite of perillyl alcohol. If so, then disulfiram might be contra-indicated with perillyl alcohol. However, disulfiram has different affinities for different isoforms of aldehyde dehydrogenase, and I can't tell you which specific ALDH is required in the perillaldehyde to perillic acid conversion.

    A quick look at wikipedia tells me that sorbitol is converted to fructose by sorbitol dehydrogenase.

    The only alcohols I'd expect to be potentially problematic with disulfiram are ones that go through a stage of being converted to an aldehyde during their metabolism. This happens to be the case for both ethanol and perillyl alcohol. A biochemist might be able to tell you which other ones to flag.

    A similar questions came up on the the cancer compass "cocktails thread"

    "Stephen and all:
    I´ve been thinking of starting disulfiram, at least around my TMZ cycles. Anyway, I am not sure about if it will interact (negatively) or not with perillyl alcohol, that I´m inhaling 4 times a day. What are your thoughts about that? Thank you!"

    "Indeed there could be an interaction between perillyl alcohol and disulfiram.
    Perillyl alcohol is first metabolized to perillaldehyde. The aldehyde dehydrogenase enzyme then converts perillaldehyde to perillic acid.
    Disulfiram is an aldehyde dehydrogenase (ALDH) inhbitor, so it would likely cause an accumulation of perillaldehyde and reduce the conversion to perillic acid.
    Whether this would increase or decrease the efficacy of perillyl alcohol, or cause an adverse reaction, I don't know. I will definitely continue to study this. I'm glad you asked."

    "So, would I likely feel the nasty effects of disulfiram on my body, like if I consumed alcohol? If the answer is yes, I´ll better pass on disulfiram!"

    "The well known ethanol-disulfiram reaction is caused by the accumulation of acetaldehyde. Disulfiram prevents the conversion of acetaldehyde to harmless acetic acid.
    According to wikipedia "Acetaldehyde is a highly unstable compound and quickly forms free radical structures which are highly toxic if not quenched by antioxidants"
    "Acetaldehyde is an irritant of the skin, eyes, mucous membranes, throat, and respiratory tract. This occurs at concentrations up to 1000 ppm. Symptoms of exposure to this compound include nausea, vomiting, headache".
    On the other hand, perillaldehyde is a very different molecule from acetaldehyde, and is used as a food additive (according to wikipedia). It is the main flavor and fragrance compoenent of perilla leaf.
    However there is no literature for the combination of perillyl alcohol plus disulfiram, and what the effects would be. I suspect the interaction would mainly be pharmacokinetic, increasing levels of perillyl alcohol and perillaldehyde in the body, and decreasing levels of perillic acid. To what extent I can't say, as this has never been tested. Anyway I doubt that you would experience the same nasty disulfiram reaction, as acetaldehyde (from ethanol) is quite a different molecule from perillaldehyde (from perillyl alcohol).",74411,128.htm

  2. Another thing to consider is that often perillyl alcohol is diluted in ethanol in an approximately 1:1 ratio before further diluting in distilled water. If this is the case, I would definitely avoid taking disulfiram anywhere near perillyl alcohol.

    Preclinical development and clinical use of perillyl alcohol for chemoprevention and cancer therapy

    "In one study with rat PC12 pheochromocytoma cells [11], perillyl aldehyde
    exerted stronger effects than POH and caused apoptosis at 200 µM. In comparison, POH
    required 500 µM for the same outcome, whereas perillic acid was inactive in these assays."

    It's possible that disulfiram could actually potentiate the effect of perillyl alcohol, by inhibiting its conversion to the less potent perillic acid. Again though, perillyl alcohol is typically diluted in ethanol, and then distilled water, according to the instructions I've seen.

  4. Thank you Stephen for your detailed answer. I need time to figure it out.