A Perspective Changing NAD+ Supplement? Nuchido Time+
Summary
TLDR本视频探讨了NAD补充剂对健康的影响。尽管先前的研究显示NAD补充剂对健康生物标志物影响不大,但最近的一项研究提出了新的视角。这项研究采用交叉设计,测试了NAD补充剂对NAD水平、细胞途径、炎症和衰老标志物的影响。结果显示,虽然NAD水平有所提高,但在其他方面效果不明显。研究者提出了一种新的补充策略,通过平衡NAD的生成和降解来提高其效果。尽管研究结果并不完全令人信服,但这一新思路为NAD补充剂的研究提供了新的方向。
Takeaways
- 🧬 NAD(烟酰胺腺嘌呤二核苷酸)是细胞内的一种重要分子,直接参与DNA修复、基因修复以及线粒体代谢等多种细胞途径。
- 👵 以往的研究表明,NAD补充剂对于健康生物标志物的影响有限,除非是年纪较大的人群(50-60岁以上)。
- 🔍 新的人类试验采用了交叉设计,通过一个月的NAD补充剂和安慰剂的交替使用,来评估NAD水平、细胞内NAD特定途径、炎症指标和衰老指标的变化。
- 🧪 研究者提出了一个新的假设,即通过补充NAD的前体分子(如NMN和NR)可能不是最佳方法,因为随着年龄的增长,将这些前体转化为NAD的酶的浓度会降低。
- 💡 研究建议直接补充NAD或使用能够平衡NAD生成和降解途径的活性分子,如香菜提取物,可能更有效。
- 📈 试验数据显示,使用NAD补充剂的参与者血液中NAD水平有所上升,而安慰剂组则没有变化。
- 📊 在细胞内,NAD补充剂似乎增加了某些基因表达调控蛋白的水平,但对线粒体基因和NAD降解酶CD38的影响不显著。
- 👵 尽管NAD补充剂似乎对减少蛋白质糖化有轻微益处,但研究者使用的统计方法存在问题,且对生物年龄变化的效果不明确。
- 🤔 尽管研究提出了有趣的假设,但作者认为证据并不具有说服力,因此对NAD补充剂的立场未变,认为它可能不值得投资,除非在特定情况下。
- 🔗 更多关于炎症效应的讨论和补充剂细节将在视频的扩展版本中提供,链接在视频描述中。
Q & A
NAD补充剂在健康生物标志物方面的效果如何?
-根据分析,NAD补充剂在健康生物标志物方面的效果并不显著,除非可能年龄较大,比如50、60岁及以上。
NAD补充剂是否被认为可以改善临床指标,例如胆固醇、血糖和胰岛素?
-NAD补充剂从未被假设可以改善这些临床指标,因此之前的研究可能没有关注NAD特定的指标。
什么是交叉设计研究?
-交叉设计研究是一种研究方法,参与者在不同时间接受不同的干预措施,这样可以减少遗传和营养对结果的影响。
NAD在细胞中的作用是什么?
-NAD是一种在细胞内发现的常见分子,直接涉及DNA修复、基因修复以及线粒体代谢等细胞途径。
研究人员提出的NAD补充剂的新假设是什么?
-研究人员提出,由于老年细胞中NAD转化酶的浓度降低,而NAD降解酶的浓度增加,因此NAD补充剂可能需要与活性分子共同摄入,以重新平衡这一平衡。
NAD补充剂直接给药与给药前体分子有何不同?
-直接给药NAD补充剂不稳定,因此研究人员使用更稳定的前体分子。他们认为,通过共同摄入可以重新平衡NAD生成和降解的活性分子,可能更有效。
研究人员在NAD补充剂试验中观察到了哪些变化?
-研究人员观察到NAD水平在补充组上升,而安慰剂组没有变化。此外,某些酶的水平有所增加,但对线粒体基因或NAD降解酶cd38的影响不大。
研究人员如何评估NAD补充剂对细胞途径的直接影响?
-研究人员通过观察NAD补充剂对组蛋白去乙酰化酶SIRT1的影响来评估其对细胞途径的直接影响,发现NAD补充剂在某些条件下增加了SIRT1的水平。
研究人员如何测量生物年龄的变化?
-研究人员通过测量血清中IgG抗体的糖基化程度来评估生物年龄的变化,但统计数据不明确,因此效果尚不明确。
NAD补充剂对蛋白质糖基化有何影响?
-尽管统计数据不明确,但NAD补充剂似乎对减少整体蛋白质糖基化有小幅度的益处。
根据这项研究,NAD补充剂是否值得购买?
-根据这项研究,NAD补充剂可能并不值得购买,除非在特定情况下,如年龄较大者。
Outlines
🧬 NAD补充剂的新研究
本段讨论了NAD补充剂在人体中的作用,特别是NMN补充剂。提到了之前的研究显示NAD补充剂对健康生物标志物的影响有限,除非是年纪较大的人群。然而,NAD补充剂并未被假设能够改善临床指标,如胆固醇、血糖、胰岛素等。最近的一项研究可能提供了不同的视角,研究者采用了交叉设计的方法,将参与者分为安慰剂组和NAD补充剂组,进行了为期一个月的干预,然后是洗脱期,最后交换条件。研究测量了NAD水平、细胞内NAD特定途径、炎症指标和衰老指标。研究者提出了一个新的假设,即之前的NAD补充剂研究可能因为使用了错误的指标而效果有限。他们提出了一个新的补充剂配方,包括能够平衡NAD生产和降解的活性分子,如欧芹提取物,可以阻断CD38,理论上可以减少其浓度。
📊 NAD补充剂对NAD水平和细胞途径的影响
本段详细讨论了NAD补充剂对血液中NAD水平的影响,以及对细胞内NAD中心途径的直接影响。研究显示,使用NAD补充剂的参与者血液中NAD水平上升,而安慰剂组则没有变化。研究还观察了NAD补充剂对组蛋白去乙酰化酶SIRT1的影响,这是一种调节细胞核内基因的酶。结果显示,NAD补充剂组在某些条件下显著增加了SIRT1蛋白的水平。然而,对线粒体基因和NAD降解酶CD38的影响并不明显,表明可能只解决了途径的一部分。此外,研究还提到了对炎症效应的评估,以及补充剂配方本身的一些细节,这些可能会在视频的扩展版本中详细讨论。
📉 NAD补充剂对衰老指标和炎症的影响
本段探讨了NAD补充剂对衰老指标的影响,特别是通过测量血清中IgG抗体的糖基化程度。糖基化程度越高,通常意味着健康状况越差。数据显示,NAD补充剂组的糖基化程度有所下降,但缺乏统计学上的明确证据。此外,作者对研究中使用的统计方法提出了批评,认为应该使用ANOVA而不是学生t检验。尽管如此,研究似乎在减少蛋白质糖基化方面显示出了一定的益处。作者还提到,将在视频的扩展版本中讨论炎症效应,但到目前为止,他认为这项研究并没有改变他对NAD补充剂的看法,认为它可能不值得投资,除非在特定情况下。
Mindmap
Keywords
💡NAD补充
💡NMN
💡临床测量
💡交叉设计
💡细胞途径
💡酶
💡衰老
💡炎症
💡统计测试
💡蛋白糖基化
Highlights
NAD补充剂在改善健康生物标志物方面的效果可能并不显著,尤其是对于较年轻的人群。
NAD补充剂从未被认为能改善胆固醇、血糖、胰岛素等临床指标。
一项新的人类试验可能提供了不同的视角,研究者从不同的角度探讨NAD补充剂。
NAD是一种在细胞内发现的常见分子,直接涉及DNA修复、基因修复和线粒体代谢等细胞途径。
试验采用了交叉设计,减少了遗传和营养对结果的影响。
研究者提出了一个假设,即以往的NAD补充方法可能是错误的。
研究者提出了一个新方法,即直接补充NAD,而不是其前体分子。
随着年龄的增长,将NAD前体转化为NAD的酶浓度降低,而降解NAD的酶浓度增加。
研究者提出了一种新的补充策略,即同时补充活性分子以平衡NAD的生成和降解。
血液NAD水平的实验表明,NAD补充剂组的NAD水平上升,而安慰剂组没有变化。
研究还观察了NAD对细胞内特定途径的直接影响,例如组蛋白去乙酰化酶SIRT1。
NAD补充剂似乎增加了SIRT1蛋白的水平,这可能对抗衰老和自噬基因有积极影响。
尽管NAD补充剂增加了某些酶的水平,但对线粒体基因和NAD降解酶CD38的影响不大。
研究者使用了基于血清中IgG抗体糖基化的实验来测量生物年龄。
尽管数据显示NAD补充剂可能减少了蛋白质糖基化,但统计数据的不明确性使得这一发现的可靠性受到质疑。
研究者认为,尽管有一些积极的迹象,但整体上并没有提供非常有力的证据来支持NAD补充剂的有效性。
作者对NAD补充剂的立场没有改变,认为它可能不值得投资,除非在特定情况下。
Transcripts
I've had some less than encouraging
words to say when it comes to NAD
supplements at least when it comes to
nmn supplementation the reason comes
down to the studies that I analyzed in
previous work offering an overall
perspective that it simply doesn't do
much in relation to various Health
biomarkers unless possibly you're a
little older say 50 60 and beyond that
said though I've also mentioned that NAD
supplements have never really been
postulated to improved clinical measures
like cholesterol blood sugar insulin and
so on so it almost seemed like a
self-defeating prophecy to have so many
human studies looking at NAD
supplementation and yet so few look at
metrics that are actually NAD specific
well fortunately we have a trial that
was recently published and was brought
to my attention by a few physionic
insiders this trial might tell a
different story because the researchers
address the NAD supplementation issue
from a different perspective which I
admittedly really like so what does this
new human trial show and does it change
my
perspective really quickly if you aren't
familiar with NAD it's a common molecule
found inside your cells and it's
directly implicated in different
cellular Pathways like DNA repair Gene
repair as well as plays a crucial role
in mitochon contral metabolism among
other Pathways without it you're dead I
really can't put it more simply than
that I'll get into some more specifics
on some of the mechanisms in a minute
but first the study the trial which was
partially industry funded split one
group of people into two groups a
placebo group which is an inert uh non
NAD intervention and the NAD
supplementation group and had each group
consume the respective intervention for
one month and then they underwent a wash
out phase a period of time where they
essentially no longer consumed anything
and return to their normal
lifestyle and then they switch
conditions this kind of study is known
as a crossover design it's a great
design that reduces the impact of
genetics and even nutrition on the
results because the same participants
are exposed to both interventions during
both time periods the participants
multiple measures taken to assess
changes in NAD levels intracellular NAD
specific Pathways inflammatory measures
and even an aging measurement admittedly
this trial seems more in line with what
preclinical studies look into which is
why I wanted to bring it up to you now
before we look at the data allow me to
explain the different hypothesis that
the researchers put forward you know how
I said most studies using NAD
supplements in humans up to now have
been pretty lackluster well sure some of
that and maybe a major reason is due to
looking at the wrong metrics to assess
nad's impact however the researchers
acknowledge there's been a limited
effectiveness of NAD supplementation and
that may be because we've been going
about supplementation
incorrectly they present this graphic
which goes over the NAD production and
utilization path pathway dominant in
cells previous research has simply given
participants NAD precursors like the
aforementioned nmn and NR which means
that they were given molecules that are
converted to NAD through these enzymatic
reactions like this one here n m PT
along with another one
nmnat so the researchers thought to
themselves well why not just give NAD
directly because no one had ever thought
of that brilliant plan before I'm
kidding that's already been tried but
NAD is apparently really unstable so
researchers use more stable precursor
molecules anyway what the researchers
point out is that the enzymes that
convert precursor molecules to NAD are
reduced in concentration in aging cells
in addition enzymes that degrade NAD
like cd38 and
nnmt there increase in concentration
with aging so think about it the pool is
less readily replenished by the
precursors because the enzymes aren't as
readily available as well as degraded
more readily due to more degradation
enzymes a double hit to the available
NAD pool so the solution would be to
co-ingested supplement with active
molecules that rebalance both sides of
the equation they show that if
Illustrated here note the different
molecules like parsley extract that
blocks cd38 thereby reducing its
concentration theoretically that is
because this is just an idea at present
we'll see if the evidence if it actually
pans out in a minute personally I like
this thinking it makes a good reasonable
sense so does the logic pan out to the
data here we're again blood NAD levels
the vertical axis is the amount of blood
NAD and the horizontal line is the time
elaps the black bars are the non NAD
supplemented placebo group and the puke
gold are the NAD supplemented group
using this magic cocktail
proposed clearly NAD levels rise in the
correct group but not in the placebo
group this is an important experiment to
indicate
if the NAD supplement is well even
absorbed it is however one drawback of
this experiment is that many previous
Studies have shown increases in blood
NAD but still have shown no effect of
NAD yes I understand that ignores some
of the context that I mentioned earlier
but I'm just saying anyway tissue NAD
would have been preferable but whatever
we don't actually care so long as the
other metrics change so do they let us
begin inside of your cells I like this
experiment because they're addressing
the actual direct effect of NAD on NAD
Centric Pathways first they look at CT
one c one is a histone deacetylase which
means that it regulates genes in the
nucleus of your cells specifically your
genes are encoded written as DNA
segments and these DNA segments are
coiled around proteins called histones
the orientation of these histones
influences if these genes are red or
suppressed the grand histone conspiracy
of suppression at any rate c one takes a
tag known as an acetes off the histone
which changes if the DNA reading
proteins can read the Gene and produce
the protein encoded I'll wrap this up by
saying that this matters because many of
the genes that c One controls are age
related genes as well as autophagy genes
okay A bit of background out of the way
and be aware that there's plenty more to
be said on that topic what did the NAD
cocktail do well I could show you this
but I doubt it would actually offer much
unless uh you know molecular biology yes
it's really ugly by the way for those in
the know anyway let's focus on the
average results in in bar graph form
we're comparing against the BL there in
both conditions that's a baseline before
supplementation of placebo or NAD
cocktail the grayscale bar is all the
placebo results over 28 days and the
vomit gold graph is the NAD cocktail the
higher the bar the more c one protein is
present clearly the placebo groups
didn't change appreciably and yet the
NAD cocktail did increase cert one at
least in certain conditions and the
others are awfully close to
statistically significant which is set
to
0.05 don't uh mind those error bars
we're we'll be uh returning to this
later in how to interpret this but
currently it seems that the cocktail
worked at increasing certainer one
Levels by the way the same was true for
one of the NAD producing enzymes
nppt how however no changes in a potent
mitochondrial Gene nor the
aforementioned cd38 which remember
degrades NAD which means that we're only
potentially addressing one part of the
pathway the production but not the
degradation all right so I planned on
covering some of the inflammatory
effects including some more specifics on
supplement cocktail itself and I'll
address some of it still but I'll likely
leave some of the finer details for the
extended version of this video which can
actually be accessed if you're a
physionic Insider the link is in the
description but fear not we still have
more to cover the video is just getting
longer than expected and YouTube is uh
really not Stellar for uh getting into
all the nitty-gritty anyway check out
the Insiders if you're so inclined and
if not let's continue with the Aging
effects for the Aging measurements they
used an experiment based on serum gly
illation of IGG
antibodies what was all that gobbley
cook they measured the amount of sugar
molecules glucose molecules found
attached to a very common antibody in
your body called IG the greater glyc
illation the worse one's Health outcomes
generally although it also depends on
the molecule attached but we won't get
into that here's the data that dotted
line is the Baseline so before
supplementation and the black dot in
line called the confidence interval is
the placebo group and the wretch gold is
the NAD cocktail if it goes down that's
a good sign it means reversal of age
unfortunately you don't see any
statistical symbols indicating
comparisons and if you read the paper
there's no indication if this difference
is statistically significant so while it
seems like there's a difference we have
no unbiased
confirmation okay that was a lot of
information so let me bore you with my
stance taking all of this into
consideration if we look at their
intriguing and wellth thought out
hypothesis it doesn't seem that they
provided very convincing evidence across
the board sure some enzymes were changed
but considering that they used the wrong
statistical tests they used a student T
Test where they should have used an
anova and the results were just barely
significant I'm inclined to dismiss this
data you may feel differently but I just
don't like it for the statistical
reasons in addition if you look at some
of the supplemental data if you compare
the placebo against the NAD condition
the results really don't look so hot for
the NAD condition which might be why
they separated the data and only
compared against Baseline within each
condition and didn't compare between
conditions then in regard to the
biological age change
I'm not sure if there's even an effect
because of the lack of clarity on the
statistics uh one positive is that they
do seem to show a small benefit in
reducing overall protein glycation and
they did apply the right statistics this
time so that data seems accurate even if
the NAD supplement colors used
throughout the study are well mustard
hurl I'll have more to say on the
inflammation effects in the extended
version but up to now I'll say this I
really like the idea and there may be
still some Merit behind it I just think
that the approach needs to be tweaked
however this study leaves my stance
unmoved in relation to NAD boosting it's
likely just isn't worth your money
except in the exceptions that I
mentioned in my full investigation on
the matter found right here
[Music]
a
[Applause]
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