22 replies to this topic

[platypus]

I think I too have noticed the effect of c60 increasing alcohol tolerance. If we assume that is a true effect it must happen in the brain and not in the liver (I do not believe c60 causes alcohol to be metabolized more quickly). What are the mechanisms how c60 could reduce perceptions of alcohol intoxication? 

[Andey]

No need to invent something new. Most probably mechanism is similar to  NAC and Vit C by limiting cells damage via antioxidant properties.

Edited by Andey, 01 July 2014 - 07:36 AM.

[platypus]

No need to invent something new. Most probably mechanism is similar to  NAC and Vit C by limiting cells damage via antioxidant properties.

I don't think so, as NAC or Vit C do not reduce alcohol intoxication in itself, but only some of the detrimental downstream effects that cause hangovers.

 

Here's what Wikipedia has to say about the pathways through which alcohol "works" in the brain: 

In the past, alcohol was believed to be a non-specific pharmacological agent affecting many neurotransmitter systems in the brain.^[5] However, molecular pharmacology studies have shown that alcohol has only a few primary targets. In some systems, these effects are facilitatory and in others inhibitory.

Among the neurotransmitter systems with enhanced functions are: GABA_A,^[6] 5-HT₃ receptor agonism^[7] (responsible for GABAergic (GABA_A receptor PAM), glycinergic, and cholinergic effects), nicotinic acetylcholine receptors.^[8]

Among those that are inhibited are: NMDA,^[7] dihydropyridine-sensitive L-type Ca2+ channels^[9] and G-protein-activated inwardly rectifying K+ channels.^[10]

The result of these direct effects is a wave of further indirect effects involving a variety of other neurotransmitter and neuropeptide systems, leading finally to the behavioural or symptomatic effects of alcohol intoxication.^[5]

 

Edited by platypus, 01 July 2014 - 08:06 AM.

[thedarkbobo]

Was going to post in other c60 topic but here it goes:

Last week

I took some c60-00 before party on purpose.

I had deep problems with getting high from lots of alcohol on that party...also no tiredness after playing volleyball...but the day after was not so good - my legs were quiet tired, but it still was quiet ok. Another epic feat I noticed and confirmed on myself, again, was no feeling of cold...when I was off it for about 4 days I think this feeling slowly started to come back.

Smoking cigar proved to be quiet relaxing. Might it just be the effect of blocking something in brain? Hard to check it just by reporting..

Edited by thedarkbobo, 03 July 2014 - 08:14 PM.

[niner]

A lot of people (pretty much everyone who both uses c60oo and drinks) have noted the effect it has on the way alcohol makes you feel.  The high feels different.  I find that the feeling of tight numbness in my face is missing.  Other things might be missing as well, although I don't feel like I'm less drunk.  I'm just as stupid and incapable of safely driving than without c60.   I consider this effect of c60 to be one of its downsides, but it's a small price to pay for the upside.   The effect may or may not be due to the ability of c60 to absorb and catalytically detoxify free radicals.  It could alternatively be a receptor mediated effect.  I find that it is very persistent, not going away over the course of a month, which is what I see with the 'mitochondrial' effects.   I've never gone longer than about five weeks between doses, and normally take 24-30mg once a month. 

[Andey]

A lot of people (pretty much everyone who both uses c60oo and drinks) have noted the effect it has on the way alcohol makes you feel.  The high feels different.  I find that the feeling of tight numbness in my face is missing.  Other things might be missing as well, although I don't feel like I'm less drunk.  I'm just as stupid and incapable of safely driving than without c60.   I consider this effect of c60 to be one of its downsides, but it's a small price to pay for the upside.   The effect may or may not be due to the ability of c60 to absorb and catalytically detoxify free radicals.  It could alternatively be a receptor mediated effect.  I find that it is very persistent, not going away over the course of a month, which is what I see with the 'mitochondrial' effects.   I've never gone longer than about five weeks between doses, and normally take 24-30mg once a month. 

 

I cant agree with on alcohol effects. On my experience its more like straight forward reducing of alcohol effects on cognitive abilities. Difference is not huge but when it came to extremes I can  retain resonable speech and muscular coordination when all friends of mine cant and this starts exactly when I started to use c60. Enough to be often mistaken as a sober person. Anyway its not a pleasant experience, so I drink only very occasionally now.

[Adaptogen]

i've noticed no real changes in my alcohol metabolism since starting c60.

I still get a pretty significant buzz after just a couple drinks. not exactly pleasant, but i've never been much of a recreational drinker so it's hard to say if it has gotten less euphoric since starting c60, or if it is merely my own mentality. it also hasn't seemed to have altered my propensity towards alcohol induced headaches, even from just a couple drinks

[niner]

 

A lot of people (pretty much everyone who both uses c60oo and drinks) have noted the effect it has on the way alcohol makes you feel.  The high feels different.  I find that the feeling of tight numbness in my face is missing.  Other things might be missing as well, although I don't feel like I'm less drunk.  I'm just as stupid and incapable of safely driving than without c60.   I consider this effect of c60 to be one of its downsides, but it's a small price to pay for the upside.   The effect may or may not be due to the ability of c60 to absorb and catalytically detoxify free radicals.  It could alternatively be a receptor mediated effect.  I find that it is very persistent, not going away over the course of a month, which is what I see with the 'mitochondrial' effects.   I've never gone longer than about five weeks between doses, and normally take 24-30mg once a month. 

 

I cant agree with on alcohol effects. On my experience its more like straight forward reducing of alcohol effects on cognitive abilities. Difference is not huge but when it came to extremes I can  retain resonable speech and muscular coordination when all friends of mine cant and this starts exactly when I started to use c60. Enough to be often mistaken as a sober person. Anyway its not a pleasant experience, so I drink only very occasionally now.

 

You might be right, Andey.  It sounds like you might be looking at a higher alcohol consumption level than I am.  It's possible that I'm just drinking more to compensate, too.  We need to get a bunch of people who've never taken c60oo, test them with specific amounts of alcohol, then on a later date dose them with c60oo and repeat the test.
 

[Adamzski]

i drink a few 500ml cans of beer each day and at times drink to extremes on weekends.

 

In the 2 months I had c60, I cant say for sure that it lessened the effects of alcohol but I am almost sure that it changed the effects and made me more clear headed and more arrogant like I felt superior to people when drinking, I did drink for several hours a couple of times while taking it. 

[Andey]

You might be right, Andey.  It sounds like you might be looking at a higher alcohol consumption level than I am.  It's possible that I'm just drinking more to compensate, too.  We need to get a bunch of people who've never taken c60oo, test them with specific amounts of alcohol, then on a later date dose them with c60oo and repeat the test.
 

We also use different administration protocols. As I read at other thread you use c60 once a month, I am on a week basis and it looks for me that greater part of alcohol protecting effects fades quickly so if I expect to participate at some party I take c60 1-2 days before.

[niner]

 

You might be right, Andey.  It sounds like you might be looking at a higher alcohol consumption level than I am.  It's possible that I'm just drinking more to compensate, too.  We need to get a bunch of people who've never taken c60oo, test them with specific amounts of alcohol, then on a later date dose them with c60oo and repeat the test.

We also use different administration protocols. As I read at other thread you use c60 once a month, I am on a week basis and it looks for me that greater part of alcohol protecting effects fades quickly so if I expect to participate at some party I take c60 1-2 days before.

 

 

By alcohol protecting effect, do you mean the immediate effect of not feeling as drunk, or the later effect of less hangover, or both?  I've been thinking lately about the various effects of c60oo.  There is probably more than one molecule involved, possibly different isomers or perhaps constitutionally different.  These could easily have different pharmacokinetics.  There could also be dose effects, where some activities show up at low doses, but others require a higher dose.

[sofaking]

After a long youth of unfettered drinking, now I tend to feel unpleasant after about two glasses of wine - so I stop drinking. It is a perfectly self-limiting system. 

 

I read about the increased alcohol tolerance attributed to C60oo, but didn't think it applied to me since I always stop at one or two glasses. Was I ever wrong, and I am writing this as a WARNING to anyone who isn't used to drinking very much. 

 

On day 2 of C60oo (2ml/day), I went to a casual dinner party with very diligent hosts who kept my wine glass full at every moment. Unfortunately I can't quantify how much I drank, but I felt great and also very thirsty! I just kept drinking and drinking and drinking and feeling awesome. If I was to guess, I probably downed nearly two bottles of wine, which is a crazy amount for me.

 

Cut to the next morning when I woke up with no memory of the end of the night, wearing all my clothes, a pile of barf next to my bed, and a hangover I haven't experienced since I was at university twenty years ago. It was a truly devastating hangover. 

 

I have barely been able to take a sip of wine in the month since then. I am not proud of this story at all - it was totally humiliating - but I wanted to share it as a warning to be very careful with your alcohol consumption while taking C60oo. 

[Sasha_]

Well, I actually have to report something slightly different after having just finished my first week on c60oo.

I bought the Vaughter one, and have taken 1 dropper every morning for 7 days.

I have not been drinking for the first 3 days, but then went on a short holiday with friends where we had quite a few drinks on several instances.

I am pretty much a lightweight when it comes to liquor, and usually don't recover well from heavy drinking nights.

I can't say I have noticed any increased tolerance in the way that I felt "compelled" to drink more than I can handle (which is what I always end up doing anyway) but it is true that the buzz was coming a bit more progressively than usual and I seemed to remain sort of clear headed for slightly longer but that's about it.

What really amazed me was that I never actually got hungover after any of those nights ! And knowing myself there is clearly two times when I should have felt like crap for a day, experiencing headache and nausea for hours, but none of it occured. I felt tired and not particularly fresh, but actually fucking amazing with regards to what I had just inflicted myself...

 

[Andey]

 

By alcohol protecting effect, do you mean the immediate effect of not feeling as drunk, or the later effect of less hangover, or both?  I've been thinking lately about the various effects of c60oo.  There is probably more than one molecule involved, possibly different isomers or perhaps constitutionally different.  These could easily have different pharmacokinetics.  There could also be dose effects, where some activities show up at low doses, but others require a higher dose.

 

 

   Both, for me it came natural that if you feel less drunk then most probably you are less drunk and should expect less hangover. I understand that its not exactly the case because alcohol effects feels differently 'in the process' and hangover feels differently too.  Anyway it is more of theoretical disscussion for me coz I havent drunk more than a bootle of beer at once for 3 months or more )

 

  As for possible mechanisms of action, you seems to be right. Its not hard to imagine that C60 have different isomers that have different effects on how liver and brain cells  works on functional level while drinking and also have some generic influence on mitochondrial function for all cells when time goes to hangovers.

[niner]

Here's what Wikipedia has to say about the pathways through which alcohol "works" in the brain: 

In the past, alcohol was believed to be a non-specific pharmacological agent affecting many neurotransmitter systems in the brain.^[5] However, molecular pharmacology studies have shown that alcohol has only a few primary targets. In some systems, these effects are facilitatory and in others inhibitory.

Among the neurotransmitter systems with enhanced functions are: GABA_A,^[6] 5-HT₃ receptor agonism^[7] (responsible for GABAergic (GABA_A receptor PAM), glycinergic, and cholinergic effects), nicotinic acetylcholine receptors.^[8]

Among those that are inhibited are: NMDA,^[7] dihydropyridine-sensitive L-type Ca2+ channels^[9] and G-protein-activated inwardly rectifying K+ channels.^[10]

The result of these direct effects is a wave of further indirect effects involving a variety of other neurotransmitter and neuropeptide systems, leading finally to the behavioural or symptomatic effects of alcohol intoxication.^[5]

 

 

Here is what Wikipedia has to say about the mechanism of action of isoflurane, an inhalation anaesthetic:

 

 

Similar to many general anesthetics, how isoflurane works remains incompletely understood. Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamates and glycine receptors, but has different effects on each receptor. It potentiates glycine receptor activity, which decreases motor function. It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels. Isoflurane also affects intracellular molecules. It activates calcium ATPase by increasing membrane fluidity. It binds to the D subunit of ATP synthase and NADH dehydrogenase.

 

 

I see some overlap with ethanol, and the part of the alcohol high that seems the most different to me is something that I find to be kind of "anaesthetic".  Here is the part that's interesting:  I've used an Advair (corticosteroid plus beta agonist) inhaler for many years.  The propellant in this and most other inhalers is a halogenated hydrocarbon that has a lot in common with typical inhalation anaesthetics.  A not-uncommon side effect of these things is having it act like an anaesthetic.  When I would take two hits in rapid succession, I could come close to passing out.  As soon as I started using c60, that effect was obliterated.   I've occasionally noticed a taste of it, but nothing like it used to be.  I wouldn't be surprised that whatever is going on with alcohol and c60 is also going on with these low molecular weight anaesthetics.  I should try to get my hands on some nitrous to see how that feels now  In the name of science...

[Adamzski]

I have a dental visit and c60 on the way, I will definitely get gas as it will be a painful visit whatever I end up getting done.

 

You think it could null the gas? Will be interesting anyway. Might need some benzos.

 

I did have a root canal without gas last year and they never believe me that I need a triple hit of the dental block, They are always surprised when even after the second injection they dig in and I almost jump out of the seat.

[Kalliste]

That is an interesting idea. I should ask a colleague to give me some local anesthetics in the name of science while I'm on C60.

Edited by Cosmicalstorm, 25 September 2014 - 10:23 AM.

[niner]

That is an interesting idea. I should ask a colleague to give me some local anesthetics in the name of science while I'm on C60.

 

It won't affect the compounds that are typically used for local anesthesia, like the *caine drugs (procaine, lidocaine, etc).    You might see a difference in the gaseous general anesthetics. 

[hav]

I've had gas at the dentist since starting c60 and it did not dull its effectiveness for me.

 

Howard

 

[Wilberforce]

Took first large-ish (10mg) single dose on Saturday and haven't craved or enjoyed alcohol since. Maybe temporary. I wondered if my alcohol craving was due to massive childhood antibiotic prescription and the ongoing candida overgrowth I've since dealt with. I.e. whether c60oo has mitigated candida.

[niner]

Alcohol craving might be self-medication, though probably not for a candida problem.  If it knocks out the craving, that would be great.  Even though it doesn't feel the same as it once did, I still like alcohol.

[Kalliste]

 

Alcohol hangover (AH) is defined as the temporary state after alcohol binge-like drinking, starting when ethanol (EtOH) is absent in plasma. Previous data indicate that AH induces mitochondrial dysfunction and free radical production in the mouse brain cortex. The aim of this work was to study mitochondrial function and reactive oxygen species production in the mouse cerebellum at the onset of AH. Male mice received a single i.p. injection of EtOH (3.8 g/kg BW) or saline solution. Mitochondrial function was evaluated 6 h after injection (AH onset). At the onset of AH, malate-glutamate and succinate-supported state 4 oxygen uptake was 2.3 and 1.9-fold increased leading to a reduction in respiratory control of 55% and 48% respectively, as compared with controls. Decreases of 38% and 16% were found in Complex I–III and IV activities. Complex II–III activity was not affected by AH. Mitochondrial membrane potential and mitochondrial permeability changes were evaluated by flow cytometry. Mitochondrial membrane potential and permeability were decreased by AH in cerebellum mitochondria. Together with this, AH induced a 25% increase in superoxide anion and a 92% increase in hydrogen peroxide production in cerebellum mitochondria. Related to nitric oxide (NO) metabolism, neuronal nitric oxide synthase (nNOS) protein expression was 52% decreased by the hangover condition compared with control group. No differences were found in cerebellum NO production between control and treated mice. The present work demonstrates that the physiopathological state of AH involves mitochondrial dysfunction in the mouse cerebellum showing the long-lasting effects of acute EtOH exposure in the central nervous system.

 

[ambivalent]

Well, this like feels like a gathering with the ghosts of longecity-past!

 

This paper may offer some possible explanation for c60oo alcohol tolerance and reduced hangovers experiences of many:

 

https://www.ncbi.nlm...46-jcm-09-03421

 

 

"In conclusion, assessment of biomarkers of alcohol metabolism suggests that fast elimination of ethanol is associated with experiencing less severe hangovers."

 

On the metabolism of ethanol:

 

"A third, relatively minor pathway involves the activity of catalase in liver peroxisomes in which ethanol functions as an electron donor for the reduction of hydrogen peroxide to water. Together, these oxidative pathways account for over 90% of alcohol elimination. The other 10% of ethanol is metabolized via non-oxidative pathways"

 

So possibly, this pathway becomes over expressed when c60 is present with the elimination not limited by the amount of H2O2, with each c60 molecule able to receive hundreds of electrons. Perhaps may indicate why I and I suspect others have found such inconsisent results with c60 and alcohol. Could it be catalase becomes depleted - when it is in abundance we experience very high tolerances when used up, c60 has much less impact on alcohol? The other two pathways appear dependent on NAD+ and NADP+. 

 

Also on oxidative stress:

 

"Free radicals, i.e., reactive oxygen species (ROS), are usually scavenged by antioxidants such as glutathione or superoxide dismutase (SOD). However, consuming large quantities of alcohol causes an imbalance between the amount of free radicals and antioxidants, i.e., excess levels of ROS such as hydroxyethyl radical (HER), called oxidative stress. The abundance of free radicals elicits a process called lipid peroxidation, in which various byproducts of alcohol breakdown, called adducts, are formed . Adducts are a combination of acetaldehyde or other aldehydes with a protein. Most notable in this regard are the aldehydes malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE). Similar to acetaldehyde, these highly reactive aldehydes cannot pass through the blood brain barrier. In the presence of acetaldehyde, MDA can react with various proteins to form malondialdehyde–acetaldehyde adducts (MAA adducts). MAA adducts are known to have proinflammatory properties. The MAA adducts are recognized by the body as foreign substances, and as a result an immune response is elicited, including increased secretion of cytokines and chemokines, as discussed elsewhere."

 

 

"To date, only one study has investigated both the biomarkers of oxidative stress and antioxidants in relationship to hangover severity. Mammen et al. examined the effect of a polyphenolic extract of clove buds (Clovinol) versus placebo on hangover severity in N = 16 healthy men, aged 25 to 55 years old. Blood ethanol and acetaldehyde concentration were determined before and at 0.5, 2, 4, and 12 h after alcohol consumption (240 mL of 42.8% McDowell’s V.S.O.P. Brandy; United Spirits Limited, Bangalore, India), and a hangover scale was completed 14 h after drinking. To assess oxidative stress, two biomarkers (8-isoprostane and malondialdehyde) were assessed, as well as two antioxidants, glutathione and superoxide dismutase (SOD). No significant difference in ethanol concentrations was found between placebo and Clovinol at any time point. After intake of alcohol alone (i.e., the placebo condition), biomarkers of oxidative stress increased over time, whereas antioxidant concentrations decreased. Mammen et al. observed a significant reduction in hangover severity after Clovinol, which was associated with a significant reduction in acetaldehyde, 8-isoprostane and malondialdehyde concentration and a significant increase in glutathione and SOD. Van de Loo et al. [43] further evaluated the placebo data of the study by Mammen et al. This evaluation revealed no significant correlations between hangover severity and blood ethanol or acetaldehyde concentrations at any time point after alcohol consumption. In addition, concentrations of the antioxidants glutathione and SOD did not significantly correlate with hangover severity at any timepoint after alcohol consumption."

 

 

So, here, perhaps, C60 acting as an SOD mimic rapidly clears up the ROS damage caused by metabolising ethanol.

 

 

Interestingly, the paper suggests that high ROS early in the drinking session correlates with less severe hangovers, whereas increased ROS later with stronger hangovers - presumably the high ROS concentration signifies a faster elimination of ethanol and so less of it crossing the BBB. 

 

Intuitively it would seem the two processes seem correlated - faster ethanol coversion and clearance of ROS: quick ethanol elimanation doesn't seem to result in ROS that lingers. But slow ethanol metabolism appears to result in ROS damage which is not so easily removed. Perhaps, it is the failure to rapidly eliminate ethanol that causes the weakened immune response to elimate the ROS.

 

Clovinol seems to have no impact on the ethanol conversion to acetaldehyde but does effect the ROS cleanup. So with c60 and alcohol so perhaps we are doing something additionally harmful while drinking - depleting endogenous catalse (scaling up as a substitute for H202 and so depleting catalase through elimating ethanol) - while perhaps preserving SOD or gluthianone (replacing their role in the ROS clean up).

 

 

For those who've experienced inconsistent effects with c60, it might be interesting to see the effects of c60 with and without catalase supplemention and the effects of catalase supplementation with and without c60.  

 

Edited by ambivalent, 03 December 2022 - 05:14 PM.