12 replies to this topic

[mrkosh1]

Hello Everyone,

 

I'm trying to interpret the literature to figure out if the metabolism of B-hydroxybutyrate (from an exogenous source) will boost the level of NAD+ over NADH or lower the level of NAD+ over NADH. 

 

Here is a paper with some information, but there are many others.

 

http://onlinelibrary...02/iub.1627/pdf

 

I'm currently taking NR, R-ALA, Ubiquinol, and intermittently fasting to boost my level of NAD+. I'm considering exogenous BHB salt. However, I don't want to take the supplement if it will reduce my NAD+ levels. 

[tunt01]

Someone else that has a better understanding of the biochemistry should comment.  But I would think that introducing any kind of energy source, even exogenous ketones, will ultimately reduce available NAD+/NADH ratio.  I remember listening to an interview of Benjamin Bikman, a staunch advocate of dietary ketosis, that introducing exogenous ketone (salts? esters?) into the body will likely result in fat production, but that it isn't mechanistically proven yet.

 

I actually have a BHB salt sitting in my kitchen cabinet and I tried it once.  But I've not heard of anyone advocating its use in an appropriate manner, unless you are going through a stroke or traumatic brain injury.  I used it on the 2nd day of a fast to accelerate my transition to ketosis once, and it worked.  But I'm probably going to pour it down the drain.

[able]

On the home page of Alivebynature.com they have a section about BHB and Nad+.  

 

They say its the opposite - BHB increases Nad+.

 

The reasons seem to make sense to me, but I haven't had a chance yet to dig in to the research they linked.   Some of that is below:

 

 

 

"A 2016 study found β-hydroxybutyrate significantly increased the phosphorylation of AMPK (16).

AMPK activation is the key signal that drives increased NAMPT, which is the rate limiting factor in the bodies constant recycling of NAD+ ®.

Metabolism of one BHB molecule require 2 molecules of NAD+ instead of the 4 molecules required in normal glucose metabolism, thereby preserving the cytoplasmic NAD+ pool (7).

• Inhibits inflammation which is a key consumer of NAD+ as we age
• Activates AMPK which drives endogenous production of NAMPT and NAD+
• Uses 50% less NAD+ in the production of ATP for basic cellular energy"

 

and

 

"The third study by Yiguo Shen and Raymond Swanson found the BHB produced in a keto diet improved the NAD+/NADH ratio to block brain inflammation following stroke and brain trauma."

Edited by able, 02 October 2017 - 10:26 PM.

[tunt01]

Makes sense, but these data points are in the setting of ketosis (nutritional, fasting).  The rats are 3 days starving, if I'm reading this right. 

 

I'm wondering what the risks are and how that might be different if insulin is around and the person isn't generating BHB from nutritional/fasting ketosis.  Introducing exogenous ketones is going to have a different effect, I think.

Edited by prophets, 02 October 2017 - 11:23 PM.

[tunt01]

HIH BIKMAN INTERVIEW

 

Watch the last part of this interview w/ Bikman.

Edited by prophets, 03 October 2017 - 11:51 AM.

[able]

Makes sense, but these data points are in the setting of ketosis (nutritional, fasting).  The rats are 3 days starving, if I'm reading this right. 

 

I'm wondering what the risks are and how that might be different if insulin is around and the person isn't already in ketosis.

 

I think some of those linked, or some others linked elsewhere on that page, are research that shows it is the BHB itself that causes the life extension benefits.  

 

This one points out that burning BHB uses 1/2 as much NAD+ :

 

β-Hydroxybutyrate: A Signaling Metabolite in starvation response 

 

"By contrast, metabolism of one BHB molecule to the same two molecules of acetyl-CoA involves conversion of only two molecules of NAD+ into NADH, both in the mitochondrion by BDH1, thereby preserving the cytoplasmic NAD+ pool (7). The cytoplasmic and mitochondrial NAD pools are relatively distinct, so the preservation of cytoplasmic NAD+ by BHB may have important cellular effects. NAD+ is a cofactor for sirtuin deacylases (such as nuclear/cytoplasmic SIRT1) as well as poly-ADP-ribose polymerase (PARP) (133)."

 

 

 

 

another one links BHB to reduced inflammation, which spares NAD+:

 

Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses

 

 

Haven't got to the other linked articles yet, but it seems to make sense.  Although not sure how BIG of a factor it is.

 

I've been taking NR and am keto for over a year, so glad to read more about this.  Think I need to look into BHB salts and other means of exogenous BHB.

Edited by able, 02 October 2017 - 11:41 PM.

[tunt01]

Yea, but everything you are saying assumes the person is already humming along in ketosis.  If you have insulin around and you are introducing exogenous ketone bodies through ketone esters or ketone salts, you aren't burning the BHB/acetyl-CoA, it's ultimately forming fat via lipogenesis.  

 

You aren't talking about the same thing I'm talking about, in terms of exogenous ketone bodies.  It's context dependent and exogenous ketones are not the same as ketones from fasting.

 

OP is talking about exogenous ketones.

 

I'm trying to interpret the literature to figure out if the metabolism of B-hydroxybutyrate (from an exogenous source) will boost the level of NAD+ over NADH or lower the level of NAD+ over NADH. 

 

 

Edited by prophets, 03 October 2017 - 11:53 AM.

[able]

Right.  I've seen references to him a lot, but never felt patient enough to watch his videos.

 

Glad I did - explains it very well.

 

(btw, the youtube link you posted was malformed and didn't work for me.  so I searched and watched several of his videos, and am not sure which one you referred to)

 

It further confirms what I've long felt - that a lifetime of insulin abuse makes us age so much faster - for a variety of reasons.

 

And being a keto fan, alternate between excitement at the benefits, and anger at the AMA and all still clinging to excess carbs.

 

I can see that exogenous ketones introduced into a high insulin environment will have little benefit.

 

OP mentioned intermittent fasting, so am guessing he is not high glucose and insulin, and seems like BHB would not lower NAD+.

 

For that matter, I still don't see anything to indicate exogenous ketones would ever be bad.  If someone is high blood glucose/insulin - BHB might provide some benefit as indicated in research, but certainly much less than in a low insulin environment.  

 

Or did I miss something?

 

 

Edited by able, 03 October 2017 - 01:30 AM.

[mrkosh1]

On the home page of Alivebynature.com they have a section about BHB and Nad+.  

 

They say its the opposite - BHB increases Nad+.

 

The reasons seem to make sense to me, but I haven't had a chance yet to dig in to the research they linked.   Some of that is below:

 

 

 

"A 2016 study found β-hydroxybutyrate significantly increased the phosphorylation of AMPK (16).

AMPK activation is the key signal that drives increased NAMPT, which is the rate limiting factor in the bodies constant recycling of NAD+ ®.

Metabolism of one BHB molecule require 2 molecules of NAD+ instead of the 4 molecules required in normal glucose metabolism, thereby preserving the cytoplasmic NAD+ pool (7).

• Inhibits inflammation which is a key consumer of NAD+ as we age
• Activates AMPK which drives endogenous production of NAMPT and NAD+
• Uses 50% less NAD+ in the production of ATP for basic cellular energy"

 

and

 

"The third study by Yiguo Shen and Raymond Swanson found the BHB produced in a keto diet improved the NAD+/NADH ratio to block brain inflammation following stroke and brain trauma."

 

Thanks for links everyone.  

[tunt01]

a bunch of stuff...

 

Or did I miss something?

 

No.  I largely agree with you.  Aside from NAD+ available, I think there is a lot we (or maybe just me) don't know about BHB as a signaling metabolite.  I guess I just worry about the extremely unnatural state of having a certain level of insulin around in the body (at a homeostatic level) and then playing with mother nature's natural machinery by dumping exogenous ketones into the system that far exceeds what the body would produce naturally.

 

I wouldn't be surprised to see that it was oncogenic in some fashion.  It isn't just the lipogenesis.  After all, diabetic ketoacidosis isn't exactly healthy.  And while I am not describing the same exact thing, the unnatural, altered physiological state can't be a good thing.

[able]

Ah,gotcha.   Makes sense that it might be problematic to force unnatural levels of ketones.

 

Edited by able, 03 October 2017 - 03:32 PM.

[ClarkSims]

 

I actually have a BHB salt sitting in my kitchen cabinet and I tried it once.  But I've not heard of anyone advocating its use in an appropriate manner, unless you are going through a stroke or traumatic brain injury.  I used it on the 2nd day of a fast to accelerate my transition to ketosis once, and it worked.  But I'm probably going to pour it down the drain.

Where did you get the BHB from? I am looking for a quality provider, who sells at a reasonable price. Pruvit, is supper expensive. I have bought from them before.

BTW, BHB has a huge following in the ketogenic diet community.

I simple Google of BHB ketogenic diet, will show a huge number of links.

I could post some links if you really want me to dig through them all.

[aribadabar]

Where did you get the BHB from?

 

There are many sellers on Amazon: https://www.amazon.c...ld-keywords=BHB