10 replies to this topic

[Cephalon]

Hi dear CR community,

I'm not sure I'm up to date with all supplements to avoid while doing CR.

From what I understand

a) nicotinamide and
b) ala

might have negative impact on CR effects. are there any other forms of Vitamin B3 to avoid during CR?

I'm sorry in case this subject has allready been discussed a lot, since I was not able to find a seperate thread on this.

I'm just about starting CR and want to make sure my effords are not all for nothing.

Additionaly, are there any supplements to support CR? I understand that resveratrol is a mimetic, but is there a synergy combinding a mimetic with CR?

Thank you all for your experiances / opinions/knowledge!

Best, Cephalon

to a)

Kevin J. Bitterman, Rozalyn M. Anderson, Haim Y. Cohen, Magda Latorre-Esteves and David A. Sinclair
Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1*
November 22, 2002 The Journal of Biological Chemistry, 277, 45099-45107

Edited by Michael, 27 December 2010 - 12:53 AM.

[Michael]

Like the reference you cite, all of the work on sirtuin inhibition by nicotinamide is in yeast, with nicotinamide applied in vitro; we don't know whether nicotinamide even can reach concentrations high enough in humans to inhibit the human homolog (SIRT1), or what dose would be required to do so, or how the pharmacokinetics, tissue distribution, and metabolism would affect NAD (let alone SIRT1) in individual target tissues.(1)

More importantly, we also don't actually know whether sirtuins are actually involved in the CR effect in even in yeast (see multiple papers by Kaeberlein's group), let alone in mammals. Notably, the putative SIRT1 activator resveratrol has no effect on lifespan in normal, genetically healthy, nonobese mice (tho' whether it actually does activate SIRT1 is in hot dispute) -- and even more strikingly, neither does transgenic overexpression of SIRT1.

OTOH, for the vast majority of people, there's no reason to take supplemental B3 (niacin OR nicotinamide) IAC.

I wouldn't worry about combining lipoic acid with CR, either, tho' again I don't see any good reason to take it if you aren't diabetic or over 60.

Reference
1. Adams JD Jr, Klaidman LK (2008). Sirtuins, Nicotinamide and Aging: A Critical Review. Letters in Drug Design & Discovery 4 (1): 44–48. doi:10.2174/157018007778992892

Edited by Michael, 27 December 2010 - 01:03 AM.

[Cephalon]

Hi Michael,


Thank you very much for taking your time to reply to my question.
First I want to thank you for bringing my post in shape!

I wasn't aware that the CR - SIRT1 connection is still in question, I will read more into this!
(thanks for refering the review on sirtuins, I will read this one today)

The reason I'm concerned about a) nicotinamide is because I was thinking about adding a B-Complex supplement, like Jarrow's B-Right to my regime, since my daily intake of some B vitamins is under the RDA. Due to my vegetarian diet I'm regularly low in Vitamin B12 (among others Vitamins e.g. D) so I will go better to supplement each B Vitamin seperately. (I will have a closer look to my cron-o-meter). Beeing a vegetarian yourself (if I remember correctly) you are familiar with this topic.

The reason I supplement b) ala is because I use ALCAR daily (1-2g) and the general oppinion seems to be that ALA is needed to prevent possibly oxidative damage to brain cells caused by ALCAR supplementation. (though I'm not sure in how far this is accurate)

I'm 25 and not diabetic.

Supplemets I regularly use are:
2g Fish oil, Vitamin D 2000IU, K (MK7 90mg), ~1g C, 1-2g ALCAR, 300mg ALA, ~3g Piracetam, ~ 10g Glutamine, ~ 5g Creatine, Ashwagandha, Magnesium, Melatonin 1mg I get the rest from my diet as far as I can see, might add Beta-Alanine


Best regards,

Cephalon

[pmcglothin]

I'm not sure I'm up to date with all supplements to avoid while doing CR.

From what I understand

a) nicotinamide and
b) ala

might have negative impact on CR effects. are there any other forms of Vitamin B3 to avoid during CR?

SNIP

I'm just about starting CR and want to make sure my (efforts) are not all for nothing.

Hi Cephalon,

Congratulations on starting CR-- a healthy way of living indeed. The question you asked is important -- a question I frequently discuss in CR way teleconferences and also here on this forum

You may find this post helpful: using Calorie Restriction Sicence to Select Supplements.

I think SIRT2 is important, along with any number of energy-sensitive regulators that become active when CR is practiced. As you enjoy your new CR life, I suggest taking a look at studies like the one below and others cited in the references. Then carefully consider any supplements you take that may conflict with the pathways you have learned about.

Good luck with your CR life!

Paul



SIRT1 Negatively Regulates the Mammalian Target of Rapamycin

Hiyaa Singhee Ghosh1¤, Michael McBurney2, Paul D. Robbins1*


The IGF/mTOR pathway, which is modulated by nutrients, growth factors, energy status and cellular stress regulates aging in various organisms. SIRT1 is a NAD+ dependent deacetylase that is known to regulate caloric restriction mediated longevity in model organisms, and has also been linked to the insulin/IGF signaling pathway. Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress. We demonstrate that SIRT1 deficiency results in elevated mTOR signaling, which is not abolished by stress conditions. The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner. Furthermore, we demonstrate that SIRT1 interacts with TSC2, a component of the mTOR inhibitory-complex upstream to mTORC1, and regulates mTOR signaling in a TSC2 dependent manner.

These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex.

Citation: Ghosh HS, McBurney M, Robbins PD (2010) SIRT1 Negatively Regulates the Mammalian Target of Rapamycin. PLoS ONE 5(2): e9199. doi:10.1371/journal.pone.0009199


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Edited by Michael, 01 January 2011 - 04:09 PM.
fixing quote

[Cephalon]

Hi Paul,

Thank you very much for all the information, wow that is a lot to read, but I got vacation so I will follow up!

First I will start with my copy of The CR Way, that should be in the mail tomorrow hopefully.

I read a post you made on your forum livingthecrway.com where you recommend Fish Oil and B12, I feel comfortable to supplement with unless I hear anything differnet.

Thank you very much for all the great information you provide here at Imminst and other resources!

Best regards,

Cephalon

[brunotto]

Greeen Tea (ECGC) inhibits p38... an important atophagy signal...

http://content.karge...&file=000257431

Besides SB203580, a specific inhibitor of the p38 MAPK, the reactive oxygen species (ROS) scavenger N-acetyl-cysteine (NAC) and a cell-permeable superoxide dismutase (SOD) mimetic strongly abrogated the stimulatory effects of rapamycin on Smad 2 and 3 phosphorylation.

http://www.ncbi.nlm....pubmed/19666112

Edited by brunotto, 01 January 2011 - 12:14 AM.

[Michael]

The reason I'm concerned about nicotinamide is because I was thinking about adding a B-Complex supplement... Due to my vegetarian diet I'm regularly low in Vitamin B12 (among others Vitamins e.g. D) so I will go better to supplement each B Vitamin seperately.

Always best.

(I will have a closer look to my cron-o-meter).

ALWAYS best.

The reason I supplement ala is because I use ALCAR daily (1-2g)

And in turn, you do that because ...?

and the general oppinion seems to be that ALA is needed to prevent possibly oxidative damage to brain cells caused by ALCAR supplementation. (though I'm not sure in how far this is accurate)

It's at least accurate at high doses, and probably worth bearing in mind -- IF you're taking ALCAR.

Supplemets I regularly use are:
2g Fish oil, Vitamin D 2000IU, K (MK7 90mg), ~1g C, 1-2g ALCAR, 300mg ALA, ~3g Piracetam, ~ 10g Glutamine, ~ 5g Creatine, Ashwagandha, Magnesium, Melatonin 1mg I get the rest from my diet as far as I can see, might add Beta-Alanine

There is nowhere near enough safety or even efficacy data on Ashwagandha for any life extensionist to be taking it. Do you have a good reason to be taking glutamine?

I recommend that people on CR avoid EPA/DHA/fish oil supplements.

You may find this post helpful: using Calorie Restriction Sicence to Select Supplements.

Any supplement that I even consider must complement, rather than conflict with, those [CR] pathways. Downregulation of the insulin/IGF-1 pathway is a good example, and there are quite a few other related pathways that work thematically with each other to move the body away from growth operations. [...] [In] a new section of LivingTheCRWay.com called “Essential Cell Signaling” one can find a diagram of the actions and description of basic CR cellular chemistry.

This is in principle good advice, except that (a) with the exception of IGF-1 and mTOR, it's not at all clear that the putative CR mediators actually have any causal relationship to the CR effect (as in the sirtuin case), and (b) it's very rarely clear whether the supplements in question actually have any real-world effect on those metabolic intermediates (as in the nicotinamide case). Eg:

Ghosh HS, McBurney M, Robbins PD (2010) SIRT1 Negatively Regulates the Mammalian Target of Rapamycin. PLoS ONE 5(2): e9199. doi:10.1371/journal.pone.0009199

... in vitro, at doses of uncertain physiological relevance in any given target tissue, and in non-CRed cells ...

Greeen Tea (ECGC) inhibits p38... an important atophagy signal...

http://content.karge...&file=000257431

... in vitro, in Human Gingival Fibroblasts, at doses of uncertain physiological relevance in any given target tissue, particularly for a heavily-biotransformed polyphenol, and in non-CRed cells that are first forced into p38 activation by dousing them with IL-17A...

(NAC) and a cell-permeable superoxide dismutase (SOD) mimetic strongly abrogated the stimulatory effects of rapamycin on Smad 2 and 3 phosphorylation.

http://www.ncbi.nlm....pubmed/19666112

... in vitro, in non-CRed rat mesangial cells that are apparently (haven't seen the full text and the abstract is silent) being first forced into profibrotic proliferation by some means and clearly being nudged into mTOR repression by rapamycin, at doses of uncertain physiological relevance in any given target tissue, assessed by indirect intermediates ...

Come on, folks: to paraphrase Walford, show me the mammalian survival curves.

Edited by Michael, 01 January 2011 - 04:44 PM.

[Cephalon]

Hi Michael,

Thank you very much for your comprehensive reply!

(my previous post posted some days ago got lost in cyber space I´m afraid, I send it from my mobile phone ...)

I use ALCAR together with Alpha GPC and Piracetam because I think they synergize well.

I use this combination as a study aid, because I'm convinced of their effect on my performance.

I can not stand stimulants (I have high blood pressure without stimulants allready) and have been in hospital due to stimulant (ab)use.

Since I'm lazy by nature that is a good way to get things going (did not notice side effects yet)

I must admit that I do not notice a change in wellbeing after droping the Ashwagandha (I wasn't sure about it anyways, due to the throid issues it might cause), though I noticed a mood lift in the beginning of use. Thank you for your input on this.

I use l-glutamine for intestinal health (this is accurate I belive, or am I out of date there?)

Could you relink your fish oil reference? The link appears to be broken.

Best regards,

Simon

[Michael]

I use l-glutamine for intestinal health (this is accurate I belive, or am I out of date there?)

You're not exactly out of date: it was always nonsense . Glutamine supplements are probably helpful in reducing intestinal atrophy during total parenteral nutrition (although some would dispute even that), but if you're a basically normal, healthy person, there's no good reason to think that you're going to have an especially healthy gut.

Could you relink your fish oil reference? The link appears to be broken.

Sorry: here is the thread on why people on CR should not take fish oil but use flax oil or other sources of alpha-linoleic acid (ALA) instead. (Actually, it's probably easiest to start here, read the links (in order), and then go back to the beginning of the thread).

And no, alpha-linolenic acid does not increase risk of prostate cancer, based on the sum of the evidence.

[Cephalon]

Hi Michael,

Thank you for your input on Glutamine. I must admit, that I do not notice any improvements or harm after using Glutamine at approx. 5g/day for 4 weeks, so I will probably drop that.

I recently added the following supplements to my regime, that do not negatively interact with CR from my understandig:

May have run short in those after around 15 years of vegetarism
500mcg Methyl B12
2 g Beta- Alanine /divided in serveral doses over the day
3 g Taurine

without regards to dietary habits
4 g Glycine
1 mg Lithium (picked this up after reading your post: the state of my pills Lithium looks really good on the paper but I could not handle even the 5mg dose, so I gave that a try. I'm not aware of any medical indication of Lithium in mycase. Just a nutritional aspect)

[lucid3]

Mods feel free to delete my post.
I need to do more reading before posting on this thread

Edited by lucid3, 30 May 2012 - 12:34 PM.