34 replies to this topic

[ozone]

I was reading on the IAS pages the history of deprenyl and then caught this bit:

Contrary to the researcher's expectations, the Deprenyl treated animals (given the high dose of Deprenyl based on the short-term studies), lived shorter lives than did the controls!

http://www.antiaging...prenylmulti.htm

So the article was talking about how important it is to take no more than the recommended dose otherwise at a high dose it can radically reduce your lifespan, instead of extending it. I just wanted to know if anyone had some info about that study because I see all these young people on this forum taking 5mg/day or what not and that type of dose isn't even recommended until you hit 60yrs, which I know a lot of people here aren't at.

So if someone can shed some light on the doses used in this study I would appreciate it.

[lemon]

A segment of the population will always abuse any substance. It's evident on these forums as well from those who post topics as "Alcohol is is My Favorite Nootropic" or "I Just Snorted Hydergine!".

[ozone]

A segment of the population will always abuse any substance.  It's evident on these forums as well from those who post topics as "Alcohol is is My Favorite Nootropic" or "I Just Snorted Hydergine!".

That's not what I mean. I have seen a lot of people who opinions I respect and who are under 45 claiming they take 5mg/day or thereabouts and it just makes me wonder when I read about a study saying the lifespan can radically decrease if you take the wrong dose. What I am trying to discover is what dose the study was performed at. If the subjects (probably rats) were given an incredible amount (the equivalent of say 50mg/day) in humans, then it would calm my fears since no one in their right mind is going to take that amount. But if instead the subjects were given the equivalent of 5mg/day then I'd start to worry if taking even 1mg/day at my age is safe.

[scottl]

Did you read this reference which Lemon posted previously:

http://www.futuresci...m/deprenyl.html

(near bottom of the page?)

Also, lifeMirage has commented on it previously.

[emerson]

Did you read this reference which Lemon posted previously:

(near bottom of the page?)

Do you mean the part about the higher SOD levels being potentially dangerous? Going by that, I assumed that any fairly high level of dosing done over long periods of an animal's life would have either a negative or negligible effect. My question is whether taking a wide spectrum of other antioxidants would protect against this negative effect, as the article seems to suggest.

[scottl]

No this part:

[A personal note: After all this, sometimes confusing, information about deprenyl, you are probably wondering how much, if any, deprenyl I take. In 1989, I began taking 15 mg. a week. I soon reduced the dosage to 5 to 10 mg. of deprenyl weekly. In 1996, I reduced my dose to 5 mg. a week and started using liquid deprenyl citrate. I also take 1000 mg. of NAC per day and at least 800 I.U. of vitamin E and 3200 mg. of vitamin C per day.]

[ozone]

No this part:

[A personal note: After all this, sometimes confusing, information about deprenyl, you are probably wondering how much, if any, deprenyl I take. In 1989, I began taking 15 mg. a week. I soon reduced the dosage to 5 to 10 mg. of deprenyl weekly. In 1996, I reduced my dose to 5 mg. a week and started using liquid deprenyl citrate. I also take 1000 mg. of NAC per day and at least 800 I.U. of vitamin E and 3200 mg. of vitamin C per day.]

Well that doctor is also in his like +60s, so it's not really imformative regarding the high-dose study his buddy conducted. Though I found this really interesting: The half-life of MAO-B inhibition in humans has been measured to be about 40 days, therefore, deprenyl probably need not be taken daily by persons who do not have a neurological disease.

Also, what do you all think about this. I tried 1/2 a tab of deprenyl today and it I felt pretty good for about 4hrs, but then I started to get really sleepy. I ended up taking a huge nap from like 4pm-10pm. In the past, I tried reboxetine which blocks dopamine reuptake in the front part of the brain in hopes that the norepherenine (I spelled that wrong) will soak longer and not reuptake through the dopamine receptors. That said, reboxetine also really make me feel sleepy and lethargic.

Does anyone have some info regarding what might be going on?

[enemy]

I'd say the most likely scenario is SOD excess becoming hydroxyl radicals.

Hijinks ensue.

[scottl]

I do not know how old you are, but why don't you review LifeMirage's posts on the topic....I could be wrong but I did not think one needed much e.g. I'm taking 1 mg 5 times per week. That might not be enough I suppose I should track this down myself at some point. Oh but I'm 45 years old.

[ozone]

I'd say the most likely scenario is SOD excess becoming hydroxyl radicals.

Hijinks ensue.

Wonderful lol. Well I only took that 1/2 tab, so I guess I'll just stick to taking KRALA and Ortho-Core until the problem goes away. Maybe I'll run to the store and pick up some blueberries and other anti-oxidants too to fix the problem. [nuk]

[ozone]

Hah, and a mere 10 min after taking some KRALA, 3 ORTHO-CORE, and some extra NAC I feel much better. [thumb]

I wish I read this part yesterday:

Obviously, if we could re-balance the antioxidant systems, the excess SOD activity could be turned from a problem to an advantage. It will be years before we know the effect of long-term low-dose deprenyl in humans. In the meantime, here are some things for anyone contemplating low-dose deprenyl for life extension to consider:

The three major natural antioxidant systems in the body are SOD, catalase, and glutathione peroxidase. Deprenyl raises SOD activity markedly, catalase activity slightly, and glutathione peroxidase activity none at all. The nutritional supplement N-Acetyl-Cysteine (NAC) raises glutathione peroxidase levels and should help to re-balance the body's natural antioxidant system in those using deprenyl.

It is probably unwise for anyone to use deprenyl without rather large doses of supplementary antioxidant vitamins, especially vitamins C and E.

The increased SOD activity induced by deprenyl is greater in females than males. The lifespan studies with deprenyl that produced positive results in animals were always done with male animals. Female animals did not have positive results in lifespan studies. The ideal dose of deprenyl in women appears to be less than the ideal dose for men. The use of supplementary antioxidants in women taking deprenyl is correspondingly more important than for men taking deprenyl.

I sure hope that going from noon-4am before I figured out this issue didn't cause any perm damange.

Edited by ozone, 23 August 2005 - 04:22 PM.

[ozone]

Another question guys. It said that the half-life of deprenyl in the brain is 40 days... so does this mean I'm going to have elevated SOD for THAT long?! I mean sheesh, if so then talk about a pain in the ass.

[nuncle]

Another question guys. It said that the half-life of deprenyl in the brain is 40 days... so does this mean I'm going to have elevated SOD for THAT long?!

No. The 40 day half-life refers to the resynthesis of MAO-B, not deprenyl itself. SOD effects are independent of deprenyl's effects as a dopamine (DA) agonist. If your goal is to elevate DA levels, you probably don't need to take deprenyl more than once every week or so. If it's the antioxidant effects you're after, you may need to take it daily--it's unclear. It's been suggested that the extended lifespan observed in mice on deprenyl is due to SOD upregulation and not MAO-B inhibition, but as yet there's really no evidence to suggest the same holds true in humans. Certainly there hasn't been any observed extension of life in Parkinson's patients taking large doses of deprenyl (though symptomatic relief is common). So, as with everything else, use your own judgment.

[ozone]

No. The 40 day half-life refers to the resynthesis of MAO-B, not deprenyl itself. SOD effects are independent of deprenyl's effects as a dopamine (DA) agonist. If your goal is to elevate DA levels, you probably don't need to take deprenyl more than once every week or so. If it's the antioxidant effects you're after, you may need to take it daily--it's unclear. It's been suggested that the extended lifespan observed in mice on deprenyl is due to SOD upregulation and not MAO-B inhibition, but as yet there's really no evidence to suggest the same holds true in humans. Certainly there hasn't been any observed extension of life in Parkinson's patients taking large doses of deprenyl (though symptomatic relief is common). So, as with everything else, use your own judgment.

Thanks for the info. Let me ask you something then. I want deprenyl to act only as a MAO-B inhibitor, and not a type-a. If I were to take 5mg/week, would it eventually turn into a type-a due to the accumulation in the brain? If that's the case then I'll simply take 1mg/week. Since you seem to know a lot on the subject I'd like to get your opinion. Thanks.

[wannafulfill]

No. The 40 day half-life refers to the resynthesis of MAO-B, not deprenyl itself. SOD effects are independent of deprenyl's effects as a dopamine (DA) agonist.

Deprenyl isn't a DA agonist. I don't have much evidence, but I personally suspect deprenyl worked for longevity in knoll's studies through MAO-B more than through SOD upregulation (making the large assumption that these effects can be separated in terms of function).

[johnmk]

Grasping at straws here, but is there any evidence that humans may be different than rats in how we respond to selegiline, and that tablet form doses up to 5mg/day might not be so harmful? Remember -- tablet form and liquid (sublingual absorption) cannot be directly compared. I believe something like 60-70% of the tablet form, when swallowed, ultimately turns into metabolites of selegiline prior to actually entering the brain, whereas sublingual absorption results in pretty much all of it reaching the brain as selegiline.

[jeromewilson]

Hmm, I guess Deprenyl could go down pretty well in Spain then, where afternoon nap attacks are part of the culture. Lucky blighters.

Sheesh, and here's me taking 10mg / day (on LifeMirage's recommendation) - live fast die young. I'm definitely going to cap up some NAC this evening.

[johnmk]

If it's any consolation, I don't believe the human studies (admittedly using diseased patients with mild and worse Parkinson's Disease) show increased mortality from using deprenyl at 10mg/day dosages. The only study that did show increased mortality was a combination study on the effects of deprenyl + l-dopa, and that study has been criticised as being poorly run and using flawed methodology that actually undermines specifically that result.

[nuncle]

Deprenyl isn't a DA agonist. I don't have much evidence, but I personally suspect deprenyl worked for longevity in knoll's studies through MAO-B more than through SOD upregulation (making the large assumption that these effects can be separated in terms of function).

Well, strictly speaking, one of deprenyl's metabolites is amphetamine, which is a DA agonist. But the amount is too small to serve a functional role. But the net effect of deprenyl's MAO-B inhibition is to increase DA levels. Synaptic DA increases on the order of 30% have been measured in some of Knoll's rat studies. Deprenyl inhibits MAO-B, which is selectively involved in DA catabolism. So in other words, with less of the stuff that breaks DA down around, DA levels rise.

As for the longevity effects, it's Knoll's own work I'm referring to--he seems to believe the longevity effects are due to SOD upregulation. Personally I haven't seen enough data to draw firm conclusions one way or the other.

[nuncle]

I want deprenyl to act only as a MAO-B inhibitor, and not a type-a. If I were to take 5mg/week, would it eventually turn into a type-a due to the accumulation in the brain? If that's the case then I'll simply take 1mg/week.

No, the effects wouldn't accumulate, because the deprenyl itself is metabolized quickly (in a matter of hours). It's the magnitude of the single dose you have to worry about. You can probably take a small dose (anything up to 10 mg/day) without much risk of MAO-A inhibition. Any number of Parkinson's patients take a 10mg dose, and to date there are very few reports of a 'cheese' effect due to Deprenyl. On the other hand, there's no long-term human data showing any benefits of taking that large a dose (except mild-to-moderate relief for Parkinsonism symptoms). So while it probably isn't going to hurt you, there's really no reason to go any higher than 5 mg/day. Certainly 5 mg/week isn't anything to worry about (unless you get worrisome side effects--everyone's biochemistry is different, so you never know).

[jeromewilson]

Thanks John, that does make me feel beter

jeromewilson did LM recommended that on forum or it was private message? would you mind saying why he recommended such relativly high dose?

It was in a PM after I had asked his advice about an anti-depressant regime. I'm guessing that he suggested that dose (actually 'between 10 and 30mg') because at that sort of level selegiline provides around 100% MAO-B inhibition, which is pretty cool, particularly when combined with DLPA or similar.

[johnmk]

I wouldn't thank me yet. I don't think we have enough data at this point, and if we do have enough data, I am not capable at this precise moment of sifting through and analyzing it. I have cut my dose down to 2.5mg/day (tablet form) from 5mg/day for the time being until this issue has obtained some measure of clarity that suits me.

[ozone]

NM

Edited by ozone, 23 August 2005 - 10:17 PM.

[johnmk]

How does a multivitamin increase catalase levels?

[ozone]

How does a multivitamin increase catalase levels?

You caught my post before I removed it. I thought that's what Vitamin C did (maybe I'm wrong).

But I did figure something out. This morning at 9am I tried 1mg of deprenyl again. I also took 650mg of KRALA and 400mg of NAC and 3xOrthoCore (multivitamin). I also had 9hrs of sleep. Around 3pm I ate some food and had another KRALA, NAC, and OrthoCore. Around 5pm though, I felt unusually tired. So tired in fact that I HAD to sleep. No if's and's or but's about it. I slept for probably 2hrs but this didn't solve this weird "tired" feeling I had. Also I felt the "odd" feeling that I felt when I initially took 2mg of deprenly about 1-2 weeks ago. What odd feeling was that? Well during this "tired" period I was having, my head would like thump ever few seconds heh. Only way to describe it is imagine you're at a complete stop physically, then all of a sudden you fly forward for like a second then come to a complete stop. My vision was fine and all that and I was still totally functionally, but that's the "feeling" that my brain was having. Really odd.

So anyway, here is the summary of what I found. Because deprenyl only lasts a few hours, I can't be feeling tired due to increased SOD. Why? Because I took KRALA, NAC, and Vitamin C at 8am (when I took the deprenly), and then again at 3pm. So any extra SOD should be removed due to the other antioxidents I was taking. So... why was I tired? I have no clue. But if this is what 1mg of deprenyl does, then I don't really want to take it again. [thumb]

[johnmk]

When specifying one's dose of deprenyl or selegiline it's helpful to specify the method of ingestion given that tablet form is roughly half as bioavailable or worse.

[ozone]

When specifying one's dose of deprenyl or selegiline it's helpful to specify the method of ingestion given that tablet form is roughly half as bioavailable or worse.

I took 2.5mg of the tablet and had this effect, and two weeks later I took 1drop of the liquid and had the same effect.

[wannafulfill]

The ideal dosing for deprenyl for life-extension purposes is a serious challenge that won't have a definitive answer unless and until costly and lengthy human trials are funded. Even as far as subjective effects, the use of deprenyl must be fine-tuned; for a given dose can cause one to be focused, another distrait. I currently use deprenyl citrate at 1mg every other day.