April 17, 2025 • 16 mins
Navigating the complex landscape of NAD+ precursors just got easier. We're cutting through scientific noise to examine a massive meta-analysis combining 40 clinical studies with nearly 15,000 participants that reveals surprising truths about these popular supplements and their effects on cholesterol.
NAD+ isn't just another molecule—it's an essential coenzyme powering countless processes throughout your body, particularly fatty acid and cholesterol metabolism. The precursors that help your body produce NAD+—nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinic acid (NA), and nicotinamide (NAM)—have generated tremendous interest in health circles, but with wildly varying claims about their benefits.
Our deep dive reveals that while these precursors collectively improved lipid profiles (reducing triglycerides, total cholesterol, LDL, and increasing HDL), the benefits weren't universal. The most striking finding? NAD+ precursors showed minimal impact in healthy individuals but produced significant improvements in those with existing cardiovascular disease or dyslipidemia. Nicotinic acid (niacin) emerged as the clear frontrunner for lipid management, working through multiple pathways to improve cholesterol markers and demonstrating real clinical benefits including reduced cardiovascular mortality.
We also explore the potential tradeoff—a slight increase in blood glucose levels associated with some precursors—and the evolving research suggesting NAM might offer lipid benefits without this downside. Whether you're considering supplementation or simply fascinated by metabolic health, this evidence-based exploration provides crucial context for understanding how these molecules might fit into your health strategy. What role might supporting NAD+ levels play in your long-term wellness plan?
Disclaimer:
The information provided in this podcast is for educational purposes only and is not intended as medical advice. Always consult with a qualified healthcare professional before making changes to your supplement regimen or health routine. Individual needs and reactions vary, so it’s important to make informed decisions with the guidance of your physician.
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Remember, informed choices lead to better health. Until next time, be well and take care of yourself.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
Welcome to the Deep Dive.
You're here, I think, becauseyou want to get right to the
heart of what matters in healthand wellness without wading
through tons of information.
Speaker 2 (00:09):
Exactly Cut through the noise.
Speaker 1 (00:10):
Right.
So today we're doing just thatfor NAD plus precursors,
specifically how they mightimpact cholesterol and well your
overall health.
Speaker 2 (00:19):
And we've got a pretty solid basis for this
discussion.
Speaker 1 (00:21):
We do.
We're looking at a bigmeta-analysis, one that combined
results from 40 clinicalstudies.
We're talking almost 15,000people involved.
Speaker 2 (00:28):
Yeah, that's Zhang and colleagues from 2022.
They really dug into how theseNAD plus precursors affect
glucose and, importantly fortoday, lipid metabolism in
humans.
Speaker 1 (00:40):
So our goal, our mission for this deep dive is
pretty clear let's understandwhat these precursors are, how
they connect to cholesterol andyou know what the actual science
is telling us about potentialbenefits.
Speaker 2 (00:51):
Let's break it down, make it make sense.
Speaker 1 (00:52):
OK, so let's start right at the beginning.
Nad plus DOH what is it?
Why should our listeners reallycare about?
Speaker 2 (00:59):
it Right NAD plus DOH .
It stands for nicotinamideadenine dinucleotide.
Bit of a mouthful.
Speaker 1 (01:06):
Yeah.
Speaker 2 (01:06):
But basically it's absolutely essential.
Think of it as a tiny criticalhelper molecule involved in well
countless processes that justkeep your body running.
Speaker 1 (01:16):
Processes like.
Speaker 2 (01:17):
Oh, all sorts Redox reactions which are fundamental
for energy transfer, directlyinvolved in energy production,
but also, crucially for today,fatty acid and cholesterol
synthesis.
Speaker 1 (01:29):
Ah, so the cholesterol connection is direct
.
Speaker 2 (01:31):
Very direct.
It's also involved in otherenergy-related things like ATP
generation that's your maincellular fuel gluconeogenesis,
making glucose and evenproducing ketone bodies.
It's really central tometabolism.
Speaker 1 (01:44):
Okay, central.
How does our body actually getthis NAD plus man?
Where does it come from?
Speaker 2 (01:50):
Well, there are two main routes.
You can make it from scratch,what's called de novo synthesis,
using tryptophan and an aminoacid.
But the main way, the reallyprimary sorts for maintaining
levels is through what we callsalvage pathways.
Speaker 1 (02:02):
Salvage pathways like recycling.
Speaker 2 (02:02):
Exactly like recycling, the body is really
efficient at taking NAD plusprecursors the building blocks
and just reusing them to makefresh NAD plus egging.
That's the dominant pathway.
Speaker 1 (02:13):
Efficient recycling always good.
Now the study.
It also mentions sirtuins.
How do they link up with NADplus?
Speaker 2 (02:20):
Ah, sirtuins.
They're a really fascinatingfamily of proteins, and the key
thing is they depend on NAD plusto do their job.
They absolutely need it tofunction, and what is their job
exactly?
They're like master regulatorsfor a huge range of cellular
functions.
We're talking about things likemanaging inflammation,
controlling cell growth, energymetabolism, how your body uses
(02:42):
fuel.
Speaker 1 (02:42):
Wow, okay.
Speaker 2 (02:43):
Yeah, and even things like your circadian rhythm.
You know your internal bodyclock, nerve function, aging
processes.
Speaker 1 (02:49):
That's a massive portfolio for one protein family
.
Speaker 2 (02:51):
It really is.
They're also implicated inthings like cancer development,
obesity, insulin resistance, howyour body handles stress.
So you see, a lot of thebiological effects we associate
with NAD+ actually happenthrough these sirtuins.
Speaker 1 (03:04):
So NAD plus enables the sirtuins to do all this
important work.
Speaker 2 (03:08):
Precisely and interestingly, the research
we're looking at highlights onespecific sirtuin SART6.
Lower levels of SART6 have beenlinked to abnormal glucose and
lipid metabolism problemshandling sugar and fats.
Speaker 1 (03:22):
Okay, that ties it all together nicely.
Nad plus is crucial.
Sirtuins need NAD plus cell andsirtuins help manage metabolism
, including cholesterol, whichbrings us logically to NAD plus
precursors.
What exactly are thesesupplements?
Speaker 2 (03:38):
Right.
So the precursors are basicallythe raw ingredients your body
uses in those salvage pathwaysto make more NAD plus cell.
Speaker 1 (03:44):
The building block.
Speaker 2 (03:45):
The building blocks exactly.
The meta-analysis focused onfour main ones that get studied
a lot Nicotinamide riboside, orNR, nicotinamide mononucleotide
NMN, nicotinic acid NA andnicotinamide NAM.
Speaker 1 (03:57):
And the idea behind taking these as supplements is
just boost your NAD plus levels.
That's the core idea Providemore raw material hoping the
body makes more NAD plus S,which might support all those
NAD plus C dependent processeslike the ones involving sirtuins
, makes sense.
So what did this bigmeta-analysis actually find?
Did taking these precursorshelp with health markers,
(04:18):
especially cholesterol?
Speaker 2 (04:20):
Okay, so the overall results, when they pulled all
the studies together, werepretty interesting.
It showed that, generallyspeaking, taking NAD plus
precursors was linked tosignificant reductions in
triglycerides.
Okay dude Total cholesterol andLDL cholesterol, the bad kind,
Also good and on the flip side,it was linked to an increase in
(04:41):
HDL, the good cholesterol.
Speaker 1 (04:43):
So positive effects on lipids overall.
Speaker 2 (04:45):
Yes, but there was a catch.
The analysis also showed atendency for these precursors as
a group to slightly increaseplasma glucose levels, blood
sugar.
Speaker 1 (04:55):
Ah, so a potential trade-off there Improvements in
fats, but maybe a negative nudgeon sugar.
Speaker 2 (05:00):
Potentially.
Yeah, it's something to beaware of from the overall
picture.
Speaker 1 (05:03):
Did all the precursors behave the same way,
or were there differencesbetween NR, na and NAM?
Nmn wasn't studied right.
Speaker 2 (05:09):
Correct.
Nmn wasn't included in thetrials they analyzed and, yes,
there were differences when theylooked at each one individually
.
Nicotinic acid or NA reallystood out.
Speaker 1 (05:21):
How so.
Speaker 2 (05:21):
NA seemed to have the most significant positive
effects across the board onlipid markers, triglycerides,
total cholesterol, ldl and HDL.
It also had an effect on plasmaglucose consistent with the
overall trend.
Speaker 1 (05:34):
So NA was the heavy hitter in this analysis for
lipids.
What about the other two, NRand NAM?
Speaker 2 (05:40):
Well for NR and NAM.
This specific meta-analysisdidn't find statistically
significant improvements inhuman lipid metabolism.
Based on the studies theyincluded.
Speaker 1 (05:49):
Okay, so maybe less effective.
Speaker 2 (05:51):
Not necessarily.
The researchers themselvespointed out something important.
There just weren't that manystudies included.
For NR and NAM specifically,the number was quite limited.
Speaker 1 (05:59):
Ah, so lack of evidence isn't necessarily
evidence of lack of effect.
Speaker 2 (06:03):
Exactly.
You can't definitively say theydon't work based on this
analysis alone, because the datapool was smaller for them and
actually, as we might discuss abit later, particularly for NA,
some newer research outside thismeta-analysis is suggesting
potential benefits for lipids.
Speaker 1 (06:18):
Okay, good to know.
Let's focus on nicotinic acidNA for a bit, then, since it
showed such strong results here.
This isn't some brand newdiscovery.
Is it NA or niacin?
Speaker 2 (06:27):
Oh, absolutely not.
Niacin has been around for along time.
It has a well-established rolein managing dyslipidemia that's
just unhealthy lipid levels andeven in treating atherosclerotic
cardiovascular disease.
Speaker 1 (06:39):
The plaque buildup in arteries.
Speaker 2 (06:41):
Right.
It's known for lowering totalcholesterol, triglycerides, ldl
and, importantly, forin HDL.
Speaker 1 (06:47):
And does that translate to actual health
outcomes, not just betternumbers?
Speaker 2 (06:50):
Yes, absolutely.
There are clinical trialsshowing that niacin therapy can
actually reduce overallmortality, the risk of dying
from cardiovascular diseases,and it can slow down the
progression of atherosclerosisitself.
So real, meaningful benefits.
Speaker 1 (07:04):
That's significant.
How does it work?
What's the mechanism behindthese cholesterol effects?
Speaker 2 (07:09):
It seems to work through a few different routes.
One key way is by promoting thebreakdown of a protein called
ApoB inside liver cells.
Apob yeah, apob is a majorstructural protein in LDL
cholesterol and otherlipoproteins that can contribute
to plaque buildup.
Niacin seems to inhibit theliver's production of
triglycerides the fats which inturn leads to more ApoB getting
(07:32):
broken down.
Speaker 1 (07:32):
Okay, so less triglyceride production means
less packaging for these badcholesterol particles.
Speaker 2 (07:37):
That's part of it, yes, and it also seems to
increase the degradation, thebreakdown, of the ApoB protein
itself.
Another mechanism involves fattissue.
How so Niacin can reduce theactivity of an enzyme in fat
cells that releases fatty acidsinto the bloodstream, so fewer
free fatty acids travel to theliver.
Speaker 1 (07:55):
And less fuel for the liver to make triglycerides.
Speaker 2 (07:57):
Exactly.
Less fatty acid uptake by theliver means less triglyceride
synthesis and, ultimately, lesssecretion of VLDL, which turns
into LDL.
Speaker 1 (08:06):
So it's hitting the supply line from fat tissue too.
Speaker 2 (08:09):
Right, and there's even evidence.
It directly inhibits a keyenzyme within the liver that's
crucial for making triglycerides, an enzyme called DGAT2.
So it's working on multiplelevels within the liver and
related tissues.
Speaker 1 (08:21):
Sounds really effective.
Speaker 2 (08:22):
Right.
Speaker 1 (08:23):
I feel like there's a but coming.
Yeah, I seem to recall a commonissue with niacin.
Speaker 2 (08:27):
You're right.
There is a well-known sideeffect.
Especially at the doses neededfor significant cholesterol
effects, usually above 50milligrams a day, it's flushing.
Speaker 1 (08:35):
Ah, the niacin flush.
Speaker 2 (08:37):
Yeah, that temporary redness, feeling of warmth,
sometimes itching.
It's generally harmless but itcan be quite uncomfortable for
people.
Definitely something to beaware of with NA.
Speaker 1 (08:47):
Okay, Now let's switch gears to nicotinamide
riboside NR.
It seems like this one gets alot of buzz lately.
What did the meta-analysis sayabout it again?
Speaker 2 (08:57):
Well, as we mentioned , this specific analysis didn't
find a statistically significanteffect from NR on lipids in the
human studies they looked at.
But it's important context thatNR is a naturally occurring
form of vitamin B3, and it'sdefinitely an NAD plus precursor
, and animal studies haveactually been quite promising.
Speaker 1 (09:15):
What do they show in animals?
Speaker 2 (09:16):
In rodent models, nr supplementation has been shown
to improve glucose tolerance,how well they handle sugar and
reduce various metabolicproblems.
So positive signs in animals.
Speaker 1 (09:27):
Any hints of that in humans, even if not
statistically significant inthis particular analysis.
Speaker 2 (09:32):
There is some other human research.
Yes, suggesting NR mightimprove lipid metabolism.
One potential way is byactivating those sirtuin
proteins we talked about earlier.
Speaker 1 (09:42):
The NAD plus 2 dependent regulators.
Speaker 2 (09:44):
Exactly.
Sirtuins play roles in fat andsugar metabolism, so activating
them could theoretically help.
But the bottom line, as themeta-analysis authors noted, is
that while NR seems pretty goodat boosting NAD plus in animals,
the human clinical trial dataon its metabolic effects,
especially lipids, is stillrelatively limited.
Speaker 1 (10:03):
Some more research needed for NR in humans.
Speaker 2 (10:05):
Definitely we need more robust human studies to
really pin down its effects.
Speaker 1 (10:09):
Okay, what about the last one, nicotinamide or NM you
mentioned?
It's related to NA, butdifferent.
Speaker 2 (10:15):
Yes, structurally similar but functionally
distinct.
Nm doesn't typically cause thatflushing effect like NA does.
Speaker 1 (10:22):
Okay, that's one difference.
Speaker 2 (10:23):
And clinically it's often used for a specific
purpose in dialysis patients tohelp manage high phosphate
levels.
Speaker 1 (10:29):
Interesting and its effect on lipids.
You said earlier studiesweren't that impressive.
Speaker 2 (10:34):
Right.
Historically, anacalia wasn'tthought to have much impact on
lipid metabolism.
That was the general viewreflected in some of the older
studies possibly included in themeta-analysis baseline.
Speaker 1 (10:46):
But you also hinted, there might be newer findings.
Speaker 2 (10:48):
Yes, and this is where it gets interesting.
While this meta-analysis didn'tshow a significant effect based
on its included studies, somemore recent research,
particularly in hemodialysispatients, has shown that no M
supplementation could actuallyimprove blood lipid profile.
Speaker 1 (11:04):
Improve lipids in dialysis patients.
Speaker 2 (11:05):
Yes, lowering things like triglycerides or
cholesterol and, crucially,these improvements were seen
without causing an increase inblood glucose levels, which is a
potential concern with NA andmaybe the precursors.
Speaker 1 (11:17):
Overall, so NA might offer lipid benefits without the
blood sugar downside, at leastin that specific group.
Speaker 2 (11:24):
It's suggestive.
Yeah, the mechanisms aren'tfully clear yet, but these newer
findings indicate NA might havesome clinical promise for
lipids, perhaps in specificsituations.
That wasn't apparent before.
Speaker 1 (11:36):
So again, the science seems to be evolving,
especially for NR and NA.
Speaker 2 (11:40):
Very much so.
It's an active area of research.
Speaker 1 (11:43):
Now something you touched on earlier who actually
benefits most?
Did the meta-analysis look intodifferent groups of people?
Speaker 2 (11:50):
Yes, they did a subgroup analysis and this was a
really key finding, I think.
Speaker 1 (11:54):
What did it show?
Speaker 2 (11:55):
It strongly suggested that NAD plus precursor
supplementation didn't reallymove the needle much on lipid
markers for people who arealready healthy.
Speaker 1 (12:04):
So if your cholesterol is fine, these might
not do much for it.
Speaker 2 (12:07):
Based on this analysis for lipid markers
specifically, that seems to bethe case.
However, the story changedcompletely when they looked at
patients with existingcardiovascular disease or
dyslipidemia.
Speaker 1 (12:18):
People who already have heart problems or abnormal
lipid levels.
Speaker 2 (12:21):
Exactly In those groups.
The supplementation did showsignificant benefits, improving
those lipid markers liketriglycerides and cholesterol.
Speaker 1 (12:29):
That makes a lot of sense.
Actually, it suggests a moretargeted effect, helping to
correct existing imbalances,rather than being a general
booster for everyone, at leastfor lipids.
Speaker 2 (12:40):
Precisely.
It really highlights that thepotential benefit likely depends
on your baseline health status.
Speaker 1 (12:46):
Of course, no study, especially a meta-analysis
combining different studies isperfect.
Speaker 2 (12:52):
What were some of the limitations or things we should
keep in mind about thisresearch?
Speaker 1 (12:55):
Good point.
There were definitely a fewfactors.
One is just the variabilitybetween the included studies.
How so Well they use differentdoses of the precursors.
Some studies combine thesupplement with lifestyle
changes like diet or exercise,or even with drugs like statins.
Others looked at the precursoralone.
That mix makes it harder toisolate the effect of just the
(13:18):
precursor.
Speaker 2 (13:19):
Yeah, lots of moving parts.
Speaker 1 (13:20):
Another thing is they only included studies published
in English, so potentiallyrelevant research in other
languages might have been missed.
Speaker 2 (13:27):
A common limitation in these types of reviews.
It is Also.
The sample sizes of theindividual studies varied quite
a bit from small trials tolarger ones.
That kind of variation orheterogeneity can influence the
overall pooled results Okay.
Speaker 1 (13:43):
Anything else.
Speaker 2 (13:44):
Just one more technical point.
The researchers noted thatdifferent studies sometimes
reported the biochemical resultslike cholesterol levels using
different units.
That adds a layer of complexitywhen trying to combine and
analyze all the data accurately.
Speaker 1 (13:58):
So while this meta-analysis gives us a really
valuable big picture view, itsounds like the researchers
themselves would say we stillneed more high-quality studies.
Speaker 2 (14:06):
Absolutely.
That was a clear conclusion.
More research is needed toconfirm these findings, to
really clarify the specificeffects of each different
precursor NR, nam, na and figureout optimal doses, who benefits
most and, importantly, thelong-term effects.
Speaker 1 (14:21):
Right, so let's try to wrap this up Based on our
deep dive today.
What are the key takeaways?
Speaker 2 (14:26):
Okay, I'd say first NAD plus precursors, especially
nicotinic acid, based on thislarge analysis, do show real
promise for improvingcholesterol and triglyceride
levels.
Speaker 1 (14:36):
But mainly in certain people.
Speaker 2 (14:37):
Right, Particularly in individuals who already have
cardiovascular disease ordiagnosed dyslipidemia.
The benefit seems less clearfor generally healthy folks
regarding lipids.
Speaker 1 (14:48):
And we need to remember the potential impact on
blood sugar.
Speaker 2 (14:51):
Yes, that's the caveat.
The overall trend suggested apossible increase in glucose,
although recent NM studies hintit might avoid this issue in
some cases.
Definitely something to monitor.
Speaker 1 (15:03):
What about NR and NM?
Speaker 2 (15:04):
For NR and NM.
This meta-analysis didn't showsignificant lipid effects, but
that might be due to limiteddata for NR and for NM.
Newer studies are actuallysuggesting potential benefits,
so their story isn't fullywritten yet.
More research is clearly neededfor both.
Speaker 1 (15:19):
A complex picture, but clearer than before, I think
.
Speaker 2 (15:22):
Hopefully.
Yes, it gives a framework forunderstanding where the science
currently stands.
Speaker 1 (15:26):
Okay, so that leads us to our final thought.
For everyone listening today,we know NAD plus is absolutely
vital.
We see these precursors havepotential, particularly NA, but
also maybe NAR and NAM down theline, especially for certain
people.
So the question to ponder iswhat are the bigger long-term
implications of activelysupporting healthy NAD plus
(15:47):
levels throughout life, and whatnew questions does this raise
for research and maybe even foryour own personal health
strategy?
Speaker 2 (15:53):
Definitely food for thought.
How do we best maintain thiscrucial molecule as we age?
Speaker 1 (15:58):
Exactly Something to keep thinking about.
Thanks for joining us for thisdeep dive.
Welcome to the Deep Dive.
You're here, I think, becauseyou want to get right to the
heart of what matters in healthand wellness without wading
through tons of information.
Speaker 2 (00:09):
Exactly Cut through the noise.
Speaker 1 (00:10):
Right.
So today we're doing just thatfor NAD plus precursors,
specifically how they mightimpact cholesterol and well your
overall health.
Speaker 2 (00:19):
And we've got a pretty solid basis for this
discussion.
Speaker 1 (00:21):
We do.
We're looking at a bigmeta-analysis, one that combined
results from 40 clinicalstudies.
We're talking almost 15,000people involved.
Speaker 2 (00:28):
Yeah, that's Zhang and colleagues from 2022.
They really dug into how theseNAD plus precursors affect
glucose and, importantly fortoday, lipid metabolism in
humans.
Speaker 1 (00:40):
So our goal, our mission for this deep dive is
pretty clear let's understandwhat these precursors are, how
they connect to cholesterol andyou know what the actual science
is telling us about potentialbenefits.
Speaker 2 (00:51):
Let's break it down, make it make sense.
Speaker 1 (00:52):
OK, so let's start right at the beginning.
Nad plus DOH what is it?
Why should our listeners reallycare about?
Speaker 2 (00:59):
it Right NAD plus DOH .
It stands for nicotinamideadenine dinucleotide.
Bit of a mouthful.
Speaker 1 (01:06):
Yeah.
Speaker 2 (01:06):
But basically it's absolutely essential.
Think of it as a tiny criticalhelper molecule involved in well
countless processes that justkeep your body running.
Speaker 1 (01:16):
Processes like.
Speaker 2 (01:17):
Oh, all sorts Redox reactions which are fundamental
for energy transfer, directlyinvolved in energy production,
but also, crucially for today,fatty acid and cholesterol
synthesis.
Speaker 1 (01:29):
Ah, so the cholesterol connection is direct
.
Speaker 2 (01:31):
Very direct.
It's also involved in otherenergy-related things like ATP
generation that's your maincellular fuel gluconeogenesis,
making glucose and evenproducing ketone bodies.
It's really central tometabolism.
Speaker 1 (01:44):
Okay, central.
How does our body actually getthis NAD plus man?
Where does it come from?
Speaker 2 (01:50):
Well, there are two main routes.
You can make it from scratch,what's called de novo synthesis,
using tryptophan and an aminoacid.
But the main way, the reallyprimary sorts for maintaining
levels is through what we callsalvage pathways.
Speaker 1 (02:02):
Salvage pathways like recycling.
Speaker 2 (02:02):
Exactly like recycling, the body is really
efficient at taking NAD plusprecursors the building blocks
and just reusing them to makefresh NAD plus egging.
That's the dominant pathway.
Speaker 1 (02:13):
Efficient recycling always good.
Now the study.
It also mentions sirtuins.
How do they link up with NADplus?
Speaker 2 (02:20):
Ah, sirtuins.
They're a really fascinatingfamily of proteins, and the key
thing is they depend on NAD plusto do their job.
They absolutely need it tofunction, and what is their job
exactly?
They're like master regulatorsfor a huge range of cellular
functions.
We're talking about things likemanaging inflammation,
controlling cell growth, energymetabolism, how your body uses
(02:42):
fuel.
Speaker 1 (02:42):
Wow, okay.
Speaker 2 (02:43):
Yeah, and even things like your circadian rhythm.
You know your internal bodyclock, nerve function, aging
processes.
Speaker 1 (02:49):
That's a massive portfolio for one protein family
.
Speaker 2 (02:51):
It really is.
They're also implicated inthings like cancer development,
obesity, insulin resistance, howyour body handles stress.
So you see, a lot of thebiological effects we associate
with NAD+ actually happenthrough these sirtuins.
Speaker 1 (03:04):
So NAD plus enables the sirtuins to do all this
important work.
Speaker 2 (03:08):
Precisely and interestingly, the research
we're looking at highlights onespecific sirtuin SART6.
Lower levels of SART6 have beenlinked to abnormal glucose and
lipid metabolism problemshandling sugar and fats.
Speaker 1 (03:22):
Okay, that ties it all together nicely.
Nad plus is crucial.
Sirtuins need NAD plus cell andsirtuins help manage metabolism
, including cholesterol, whichbrings us logically to NAD plus
precursors.
What exactly are thesesupplements?
Speaker 2 (03:38):
Right.
So the precursors are basicallythe raw ingredients your body
uses in those salvage pathwaysto make more NAD plus cell.
Speaker 1 (03:44):
The building block.
Speaker 2 (03:45):
The building blocks exactly.
The meta-analysis focused onfour main ones that get studied
a lot Nicotinamide riboside, orNR, nicotinamide mononucleotide
NMN, nicotinic acid NA andnicotinamide NAM.
Speaker 1 (03:57):
And the idea behind taking these as supplements is
just boost your NAD plus levels.
That's the core idea Providemore raw material hoping the
body makes more NAD plus S,which might support all those
NAD plus C dependent processeslike the ones involving sirtuins
, makes sense.
So what did this bigmeta-analysis actually find?
Did taking these precursorshelp with health markers,
(04:18):
especially cholesterol?
Speaker 2 (04:20):
Okay, so the overall results, when they pulled all
the studies together, werepretty interesting.
It showed that, generallyspeaking, taking NAD plus
precursors was linked tosignificant reductions in
triglycerides.
Okay dude Total cholesterol andLDL cholesterol, the bad kind,
Also good and on the flip side,it was linked to an increase in
(04:41):
HDL, the good cholesterol.
Speaker 1 (04:43):
So positive effects on lipids overall.
Speaker 2 (04:45):
Yes, but there was a catch.
The analysis also showed atendency for these precursors as
a group to slightly increaseplasma glucose levels, blood
sugar.
Speaker 1 (04:55):
Ah, so a potential trade-off there Improvements in
fats, but maybe a negative nudgeon sugar.
Speaker 2 (05:00):
Potentially.
Yeah, it's something to beaware of from the overall
picture.
Speaker 1 (05:03):
Did all the precursors behave the same way,
or were there differencesbetween NR, na and NAM?
Nmn wasn't studied right.
Speaker 2 (05:09):
Correct.
Nmn wasn't included in thetrials they analyzed and, yes,
there were differences when theylooked at each one individually
.
Nicotinic acid or NA reallystood out.
Speaker 1 (05:21):
How so.
Speaker 2 (05:21):
NA seemed to have the most significant positive
effects across the board onlipid markers, triglycerides,
total cholesterol, ldl and HDL.
It also had an effect on plasmaglucose consistent with the
overall trend.
Speaker 1 (05:34):
So NA was the heavy hitter in this analysis for
lipids.
What about the other two, NRand NAM?
Speaker 2 (05:40):
Well for NR and NAM.
This specific meta-analysisdidn't find statistically
significant improvements inhuman lipid metabolism.
Based on the studies theyincluded.
Speaker 1 (05:49):
Okay, so maybe less effective.
Speaker 2 (05:51):
Not necessarily.
The researchers themselvespointed out something important.
There just weren't that manystudies included.
For NR and NAM specifically,the number was quite limited.
Speaker 1 (05:59):
Ah, so lack of evidence isn't necessarily
evidence of lack of effect.
Speaker 2 (06:03):
Exactly.
You can't definitively say theydon't work based on this
analysis alone, because the datapool was smaller for them and
actually, as we might discuss abit later, particularly for NA,
some newer research outside thismeta-analysis is suggesting
potential benefits for lipids.
Speaker 1 (06:18):
Okay, good to know.
Let's focus on nicotinic acidNA for a bit, then, since it
showed such strong results here.
This isn't some brand newdiscovery.
Is it NA or niacin?
Speaker 2 (06:27):
Oh, absolutely not.
Niacin has been around for along time.
It has a well-established rolein managing dyslipidemia that's
just unhealthy lipid levels andeven in treating atherosclerotic
cardiovascular disease.
Speaker 1 (06:39):
The plaque buildup in arteries.
Speaker 2 (06:41):
Right.
It's known for lowering totalcholesterol, triglycerides, ldl
and, importantly, forin HDL.
Speaker 1 (06:47):
And does that translate to actual health
outcomes, not just betternumbers?
Speaker 2 (06:50):
Yes, absolutely.
There are clinical trialsshowing that niacin therapy can
actually reduce overallmortality, the risk of dying
from cardiovascular diseases,and it can slow down the
progression of atherosclerosisitself.
So real, meaningful benefits.
Speaker 1 (07:04):
That's significant.
How does it work?
What's the mechanism behindthese cholesterol effects?
Speaker 2 (07:09):
It seems to work through a few different routes.
One key way is by promoting thebreakdown of a protein called
ApoB inside liver cells.
Apob yeah, apob is a majorstructural protein in LDL
cholesterol and otherlipoproteins that can contribute
to plaque buildup.
Niacin seems to inhibit theliver's production of
triglycerides the fats which inturn leads to more ApoB getting
(07:32):
broken down.
Speaker 1 (07:32):
Okay, so less triglyceride production means
less packaging for these badcholesterol particles.
Speaker 2 (07:37):
That's part of it, yes, and it also seems to
increase the degradation, thebreakdown, of the ApoB protein
itself.
Another mechanism involves fattissue.
How so Niacin can reduce theactivity of an enzyme in fat
cells that releases fatty acidsinto the bloodstream, so fewer
free fatty acids travel to theliver.
Speaker 1 (07:55):
And less fuel for the liver to make triglycerides.
Speaker 2 (07:57):
Exactly.
Less fatty acid uptake by theliver means less triglyceride
synthesis and, ultimately, lesssecretion of VLDL, which turns
into LDL.
Speaker 1 (08:06):
So it's hitting the supply line from fat tissue too.
Speaker 2 (08:09):
Right, and there's even evidence.
It directly inhibits a keyenzyme within the liver that's
crucial for making triglycerides, an enzyme called DGAT2.
So it's working on multiplelevels within the liver and
related tissues.
Speaker 1 (08:21):
Sounds really effective.
Speaker 2 (08:22):
Right.
Speaker 1 (08:23):
I feel like there's a but coming.
Yeah, I seem to recall a commonissue with niacin.
Speaker 2 (08:27):
You're right.
There is a well-known sideeffect.
Especially at the doses neededfor significant cholesterol
effects, usually above 50milligrams a day, it's flushing.
Speaker 1 (08:35):
Ah, the niacin flush.
Speaker 2 (08:37):
Yeah, that temporary redness, feeling of warmth,
sometimes itching.
It's generally harmless but itcan be quite uncomfortable for
people.
Definitely something to beaware of with NA.
Speaker 1 (08:47):
Okay, Now let's switch gears to nicotinamide
riboside NR.
It seems like this one gets alot of buzz lately.
What did the meta-analysis sayabout it again?
Speaker 2 (08:57):
Well, as we mentioned , this specific analysis didn't
find a statistically significanteffect from NR on lipids in the
human studies they looked at.
But it's important context thatNR is a naturally occurring
form of vitamin B3, and it'sdefinitely an NAD plus precursor
, and animal studies haveactually been quite promising.
Speaker 1 (09:15):
What do they show in animals?
Speaker 2 (09:16):
In rodent models, nr supplementation has been shown
to improve glucose tolerance,how well they handle sugar and
reduce various metabolicproblems.
So positive signs in animals.
Speaker 1 (09:27):
Any hints of that in humans, even if not
statistically significant inthis particular analysis.
Speaker 2 (09:32):
There is some other human research.
Yes, suggesting NR mightimprove lipid metabolism.
One potential way is byactivating those sirtuin
proteins we talked about earlier.
Speaker 1 (09:42):
The NAD plus 2 dependent regulators.
Speaker 2 (09:44):
Exactly.
Sirtuins play roles in fat andsugar metabolism, so activating
them could theoretically help.
But the bottom line, as themeta-analysis authors noted, is
that while NR seems pretty goodat boosting NAD plus in animals,
the human clinical trial dataon its metabolic effects,
especially lipids, is stillrelatively limited.
Speaker 1 (10:03):
Some more research needed for NR in humans.
Speaker 2 (10:05):
Definitely we need more robust human studies to
really pin down its effects.
Speaker 1 (10:09):
Okay, what about the last one, nicotinamide or NM you
mentioned?
It's related to NA, butdifferent.
Speaker 2 (10:15):
Yes, structurally similar but functionally
distinct.
Nm doesn't typically cause thatflushing effect like NA does.
Speaker 1 (10:22):
Okay, that's one difference.
Speaker 2 (10:23):
And clinically it's often used for a specific
purpose in dialysis patients tohelp manage high phosphate
levels.
Speaker 1 (10:29):
Interesting and its effect on lipids.
You said earlier studiesweren't that impressive.
Speaker 2 (10:34):
Right.
Historically, anacalia wasn'tthought to have much impact on
lipid metabolism.
That was the general viewreflected in some of the older
studies possibly included in themeta-analysis baseline.
Speaker 1 (10:46):
But you also hinted, there might be newer findings.
Speaker 2 (10:48):
Yes, and this is where it gets interesting.
While this meta-analysis didn'tshow a significant effect based
on its included studies, somemore recent research,
particularly in hemodialysispatients, has shown that no M
supplementation could actuallyimprove blood lipid profile.
Speaker 1 (11:04):
Improve lipids in dialysis patients.
Speaker 2 (11:05):
Yes, lowering things like triglycerides or
cholesterol and, crucially,these improvements were seen
without causing an increase inblood glucose levels, which is a
potential concern with NA andmaybe the precursors.
Speaker 1 (11:17):
Overall, so NA might offer lipid benefits without the
blood sugar downside, at leastin that specific group.
Speaker 2 (11:24):
It's suggestive.
Yeah, the mechanisms aren'tfully clear yet, but these newer
findings indicate NA might havesome clinical promise for
lipids, perhaps in specificsituations.
That wasn't apparent before.
Speaker 1 (11:36):
So again, the science seems to be evolving,
especially for NR and NA.
Speaker 2 (11:40):
Very much so.
It's an active area of research.
Speaker 1 (11:43):
Now something you touched on earlier who actually
benefits most?
Did the meta-analysis look intodifferent groups of people?
Speaker 2 (11:50):
Yes, they did a subgroup analysis and this was a
really key finding, I think.
Speaker 1 (11:54):
What did it show?
Speaker 2 (11:55):
It strongly suggested that NAD plus precursor
supplementation didn't reallymove the needle much on lipid
markers for people who arealready healthy.
Speaker 1 (12:04):
So if your cholesterol is fine, these might
not do much for it.
Speaker 2 (12:07):
Based on this analysis for lipid markers
specifically, that seems to bethe case.
However, the story changedcompletely when they looked at
patients with existingcardiovascular disease or
dyslipidemia.
Speaker 1 (12:18):
People who already have heart problems or abnormal
lipid levels.
Speaker 2 (12:21):
Exactly In those groups.
The supplementation did showsignificant benefits, improving
those lipid markers liketriglycerides and cholesterol.
Speaker 1 (12:29):
That makes a lot of sense.
Actually, it suggests a moretargeted effect, helping to
correct existing imbalances,rather than being a general
booster for everyone, at leastfor lipids.
Speaker 2 (12:40):
Precisely.
It really highlights that thepotential benefit likely depends
on your baseline health status.
Speaker 1 (12:46):
Of course, no study, especially a meta-analysis
combining different studies isperfect.
Speaker 2 (12:52):
What were some of the limitations or things we should
keep in mind about thisresearch?
Speaker 1 (12:55):
Good point.
There were definitely a fewfactors.
One is just the variabilitybetween the included studies.
How so Well they use differentdoses of the precursors.
Some studies combine thesupplement with lifestyle
changes like diet or exercise,or even with drugs like statins.
Others looked at the precursoralone.
That mix makes it harder toisolate the effect of just the
(13:18):
precursor.
Speaker 2 (13:19):
Yeah, lots of moving parts.
Speaker 1 (13:20):
Another thing is they only included studies published
in English, so potentiallyrelevant research in other
languages might have been missed.
Speaker 2 (13:27):
A common limitation in these types of reviews.
It is Also.
The sample sizes of theindividual studies varied quite
a bit from small trials tolarger ones.
That kind of variation orheterogeneity can influence the
overall pooled results Okay.
Speaker 1 (13:43):
Anything else.
Speaker 2 (13:44):
Just one more technical point.
The researchers noted thatdifferent studies sometimes
reported the biochemical resultslike cholesterol levels using
different units.
That adds a layer of complexitywhen trying to combine and
analyze all the data accurately.
Speaker 1 (13:58):
So while this meta-analysis gives us a really
valuable big picture view, itsounds like the researchers
themselves would say we stillneed more high-quality studies.
Speaker 2 (14:06):
Absolutely.
That was a clear conclusion.
More research is needed toconfirm these findings, to
really clarify the specificeffects of each different
precursor NR, nam, na and figureout optimal doses, who benefits
most and, importantly, thelong-term effects.
Speaker 1 (14:21):
Right, so let's try to wrap this up Based on our
deep dive today.
What are the key takeaways?
Speaker 2 (14:26):
Okay, I'd say first NAD plus precursors, especially
nicotinic acid, based on thislarge analysis, do show real
promise for improvingcholesterol and triglyceride
levels.
Speaker 1 (14:36):
But mainly in certain people.
Speaker 2 (14:37):
Right, Particularly in individuals who already have
cardiovascular disease ordiagnosed dyslipidemia.
The benefit seems less clearfor generally healthy folks
regarding lipids.
Speaker 1 (14:48):
And we need to remember the potential impact on
blood sugar.
Speaker 2 (14:51):
Yes, that's the caveat.
The overall trend suggested apossible increase in glucose,
although recent NM studies hintit might avoid this issue in
some cases.
Definitely something to monitor.
Speaker 1 (15:03):
What about NR and NM?
Speaker 2 (15:04):
For NR and NM.
This meta-analysis didn't showsignificant lipid effects, but
that might be due to limiteddata for NR and for NM.
Newer studies are actuallysuggesting potential benefits,
so their story isn't fullywritten yet.
More research is clearly neededfor both.
Speaker 1 (15:19):
A complex picture, but clearer than before, I think
.
Speaker 2 (15:22):
Hopefully.
Yes, it gives a framework forunderstanding where the science
currently stands.
Speaker 1 (15:26):
Okay, so that leads us to our final thought.
For everyone listening today,we know NAD plus is absolutely
vital.
We see these precursors havepotential, particularly NA, but
also maybe NAR and NAM down theline, especially for certain
people.
So the question to ponder iswhat are the bigger long-term
implications of activelysupporting healthy NAD plus
(15:47):
levels throughout life, and whatnew questions does this raise
for research and maybe even foryour own personal health
strategy?
Speaker 2 (15:53):
Definitely food for thought.
How do we best maintain thiscrucial molecule as we age?
Speaker 1 (15:58):
Exactly Something to keep thinking about.
Thanks for joining us for thisdeep dive.
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