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 =?UTF-8?q?hat_They_Hoped_From_NAD+?=
From: Derek from Research Radar <derekpruski@substack.com>
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View this post on the web at https://derekpruski.substack.com/p/nmn-vs-nr-a=
-deep-dive-for-researchers

Read this first: Everything below is for research and educational purposes =
only. Nothing here is medical advice. If you=E2=80=99re considering anythin=
g for personal use, that=E2=80=99s a conversation for a qualified clinician=
 =E2=80=94 not a Substack post.
The Landscape
The NAD+ conversation has gotten messy. IV NAD+. SubQ NAD+. NMN. NR. NA. NA=
M. Every podcast names a different =E2=80=9Cbest=E2=80=9D precursor.
A lot of researchers have looked at NAD+ protocols =E2=80=94 usually subQ, =
sometimes IV =E2=80=94 and walked away unimpressed by the data. Small effec=
ts, often nothing you can clearly tie back to the protocol. Then they read =
about NMN or NR and wonder if the field picked the wrong format from the st=
art.
That confusion isn=E2=80=99t on the researcher. The NAD+ space has three re=
al debates running at the same time:
Does direct NAD+ administration even work, or does the molecule get broken =
down before it can do anything useful inside cells?
Between NMN and NR, is there a real difference, or are they basically the s=
ame?
What dose, how long, and what outcomes are realistic?
This post walks through all three.
NAD+ Biology In One Page
NAD+ (nicotinamide adenine dinucleotide) is a helper molecule used in almos=
t every metabolic process =E2=80=94 ATP production, DNA repair, sirtuin act=
ivity, PARP activity, mitochondrial function. It exists in every cell, and =
cells contain far more NAD+ than they do its precursors.
NAD+ levels drop with age. That drop tracks with mitochondrial dysfunction,=
 more DNA damage, lower sirtuin activity, and most of the hallmarks of agin=
g. Whether the drop is the cause or just a symptom is debated, but the link=
 is solid.
You don=E2=80=99t get NAD+ directly from food in any real amount. The body =
builds NAD+ from precursors through a few different pathways:
Tryptophan (de novo pathway) =E2=80=94 slow, inefficient
NA / nicotinic acid (Preiss-Handler pathway) =E2=80=94 causes flushing, wel=
l-studied
NAM / nicotinamide (salvage pathway) =E2=80=94 the main recycling route
NR / nicotinamide riboside =E2=80=94 joins the salvage pathway one step fur=
ther along
NMN / nicotinamide mononucleotide =E2=80=94 one step closer to NAD+ than NR
The supplement world mostly lives in the last two. Everything else is eithe=
r old news (niacin) or impractical (tryptophan loading).
The SubQ NAD+ Debate
This is the elephant in the room, and it=E2=80=99s why a lot of researchers=
 feel the broader NAD+ story isn=E2=80=99t delivering.
The pro-subQ argument is simple: oral NAD+ has terrible bioavailability (of=
ten cited at 2-10%), so the logic goes =E2=80=94 skip the gut, put it direc=
tly into the bloodstream, and it should work better. SubQ NAD+ administrati=
on has become popular at longevity clinics because it=E2=80=99s more practi=
cal than IV but supposedly delivers more than oral.
The skeptical argument is about mechanism. NAD+ is a big, charged molecule.=
 Cells don=E2=80=99t have a known door (transporter) that lets a circulatin=
g NAD+ molecule walk into a muscle cell or neuron and start working as a co=
enzyme. The body builds its NAD+ pool inside cells from precursors. It does=
n=E2=80=99t import NAD+ from outside.
Eric Verdin, President of the Buck Institute for Research on Aging, has bee=
n the loudest voice on this. His position: when you administer NAD+ subQ or=
 IV, most of it gets broken down to nicotinamide before it ever reaches cel=
ls. The end result inside cells is basically the same as if you=E2=80=99d j=
ust taken nicotinamide orally. Charles Brenner (the researcher who first id=
entified NR as an NAD+ precursor) has been even blunter =E2=80=94 he=E2=80=
=99s called NAD+ administration outside the cell mechanistically incoherent=
=2E
So what does that mean for the research showing modest or no benefit from s=
ubQ NAD+? Two fair reads:
The molecule gets chopped up into nicotinamide and the rest of the NAD+ str=
ucture within minutes of administration. What actually raises cellular NAD+=
 is just nicotinamide =E2=80=94 same as a B3 vitamin. Plausible. Fits the b=
iochemistry.
Or: it briefly raises NAD+ in the blood, but tissue NAD+ =E2=80=94 which is=
 what actually matters =E2=80=94 barely moves because cells make their own =
and don=E2=80=99t need imported NAD+.
Either way, the end result is the same: subQ NAD+ may be functioning as nic=
otinamide administration. And as the next section covers, nicotinamide is t=
he weakest of the precursors for keeping NAD+ high over time.
This is the key context for anyone reading the NAD+ literature. Weak result=
s from subQ NAD+ research aren=E2=80=99t evidence that NAD+ doesn=E2=80=99t=
 matter. They=E2=80=99re evidence that the delivery format probably isn=E2=
=80=99t doing what the marketing claims.
NMN vs NR =E2=80=94 What They Actually Are
NR (nicotinamide riboside) is nicotinamide attached to a ribose sugar. Disc=
overed as an NAD+ precursor by Charles Brenner=E2=80=99s lab in 2004. Paten=
ted and sold by ChromaDex under the Niagen brand. The most studied NAD+ pre=
cursor in humans by trial count.
NMN (nicotinamide mononucleotide) is NR with a phosphate group added. One e=
nzymatic step closer to NAD+ in the pathway. Closely tied to David Sinclair=
=E2=80=99s lab at Harvard, which published the landmark 2013 paper showing =
NMN reversed multiple aging markers in mice.
The two are more similar than different. For years there was a debate about=
 whether NMN gets absorbed whole (through a gut transporter called Slc12a8)=
 or first gets stripped down to NR in the gut and then taken up. The 2025 C=
hristen et al. study in Nature Metabolism mostly settled it: NMN=E2=80=99s =
path through nicotinamide and then nicotinic acid looked a lot like NR=E2=
=80=99s, and both changed gut bacteria in similar ways.
Practically: NMN and NR aren=E2=80=99t fundamentally different molecules. T=
hey feed into the same pathway, raise NAD+ to similar levels at similar dos=
es, and have overlapping (but not identical) downstream effects.
The differences that do matter:
Stability and delivery. NMN holds up better in water. NR holds up better as=
 a chloride salt in capsules. Both come in solid oral capsule forms now.
Regulatory status. NR has been an established dietary supplement in the US =
for years. NMN had a rougher path =E2=80=94 the FDA pulled it from the supp=
lement category in November 2022 over the drug preclusion clause (MetroBiot=
ech=E2=80=99s MIB-626 was in drug development). After a multi-year fight le=
d by the Natural Products Association, the FDA reversed itself on September=
 29, 2025, confirming NMN is lawful as a dietary supplement. As of late 202=
5, NMN is back on Amazon and standard retail.
Evidence depth. NR has a longer track record of human trials. NMN=E2=80=99s=
 evidence base is catching up fast =E2=80=94 as of mid-2025, at least five =
NMN RCTs and ten NR RCTs have reported metabolic outcomes, with more on the=
 way.
What The Human Data Shows
This is where the picture sharpens. We=E2=80=99re not just looking at roden=
ts anymore.
The head-to-head trial (Christen et al., 2025, Nature Metabolism). The firs=
t direct human comparison of NR, NMN, and nicotinamide. NR and NMN both rou=
ghly doubled blood NAD+ over 14 days. Nicotinamide didn=E2=80=99t. Short-te=
rm, nicotinamide raised NAD+ faster, but the effect didn=E2=80=99t last. Th=
e conclusion: NR and NMN are comparable for keeping NAD+ elevated long-term=
=2E Nicotinamide isn=E2=80=99t a good pick for sustained elevation.
NR human trials (overall). Across multiple placebo-controlled trials at dos=
es from 100 mg to 2000 mg/day, NR reliably raises whole-blood NAD+, is well=
-tolerated, and has shown some improvements in muscle acetylcarnitine level=
s, arterial stiffness, blood pressure, and inflammatory markers. Honest sum=
mary: NAD+ goes up, safety is clean, functional outcomes are hit-or-miss. T=
he twin study (Lapatto et al., 2023) used escalating NR doses of 250 to 100=
0 mg/day for 5 months in BMI-discordant identical twins. It showed improved=
 muscle mitochondrial numbers, better myoblast differentiation, and changes=
 in gut microbiota =E2=80=94 but no real improvement in body fat or metabol=
ic health.
NMN human trials. The 250 mg/day Japanese trial in older men (Igarashi et a=
l., 2022) showed measurable NAD+ elevation and =E2=80=9Cnominally significa=
nt=E2=80=9D improvements in muscle function over 6-12 weeks. The MIB-626 tr=
ial in hospitalized COVID-19 patients with acute kidney injury (2 g/day for=
 14 days) showed safe NAD+ elevation in a clinical setting. More recent NMN=
 trials have reported improvements in sleep quality, walking speed in older=
 adults, insulin sensitivity, and exercise performance.
Where both come up short. Neither NMN nor NR has been shown to extend human=
 lifespan, prevent specific age-related diseases, or reverse aging in any m=
eaningful way. The trials are short (usually 8-12 weeks, longest around 5-6=
 months), small (median around 40 people), and mostly in healthy population=
s where there isn=E2=80=99t much room to improve. What the trials do show c=
onsistently: NAD+ goes up with both, safety is good at doses up to 2 g/day,=
 and downstream effects are real but modest.
The honest takeaway from the literature: a big chunk of the disappointment =
in NAD+ outcomes probably comes down to the wrong precursor (oral nicotinam=
ide alone isn=E2=80=99t great), the wrong delivery format (subQ NAD+ may no=
t actually do what the marketing claims), or expecting too much of a =E2=80=
=9Cfeel=E2=80=9D from raising NAD+ in the first place.
Why NAD+ Interventions Don=E2=80=99t Feel Like Much
Worth its own section because it trips up almost every read of the literatu=
re.
The marketing around NAD+ =E2=80=94 especially IV and subQ =E2=80=94 strong=
ly implies an experience: energy, mental clarity, almost a stimulant-like e=
ffect. Some user reports describe that. A lot don=E2=80=99t. Controlled tri=
als don=E2=80=99t even measure =E2=80=9Cfeel=E2=80=9D as a primary outcome.
Here=E2=80=99s the mechanism reason: NAD+ is a coenzyme. Coenzymes don=E2=
=80=99t usually produce a felt effect. They=E2=80=99re tools that enzymes u=
se to run reactions in the background. Raising NAD+ by 50% doesn=E2=80=99t =
produce a sensation any more than raising cellular ATP would. Both are nece=
ssary for cells to function. Neither is something you actually feel.
What trials do show with NMN or NR at adequate doses over months: better ex=
ercise tolerance, small gains in muscle endurance or strength, better sleep=
 in some subgroups, lower inflammation markers, lower acylcarnitines (mitoc=
hondria using fuel more efficiently), and sometimes better insulin sensitiv=
ity. None of these are dramatic. Most are measurable, not noticeable.
If NAD+ protocols are being judged against a stimulant-like response, they=
=E2=80=99ll look disappointing no matter the format. That=E2=80=99s not the=
 protocol failing. That=E2=80=99s the marketing setting bad expectations.
Dosing Patterns From The Literature
What the trials have actually used =E2=80=94 not what supplement companies =
recommend.
NR. Single-dose pharmacokinetics tested at 100, 300, and 1000 mg, with dose=
-dependent increases in blood NAD+. Long-term dosing trials have used 250 m=
g up to 2000 mg/day. 1000 mg/day (usually 500 mg twice a day) is the most-s=
tudied dose with functional results. Time to measurable NAD+ rise: days. Ti=
me to functional effects: 8-12 weeks at minimum.
NMN. Single-dose safety established at 100, 250, and 500 mg in healthy Japa=
nese men. Long-term trials have used 250 mg/day to 1250 mg/day for 4-12 wee=
ks. 500-1000 mg/day is where most positive results come from. The 250 mg/da=
y older-men trial showed effects but smaller ones. Time course is similar t=
o NR =E2=80=94 NAD+ rises in days, functional changes show up at 6-12 weeks=
 and beyond.
Timing. Both NMN and NR have been used with and without food in trials. Foo=
d doesn=E2=80=99t really get in the way of absorption. Morning dosing is th=
e convention but not based on evidence.
Combination protocols. Some longevity clinics use subQ NAD+ as a =E2=80=9Cl=
oading=E2=80=9D phase and then oral NMN or NR for maintenance. The reasonin=
g is shaky for the reasons covered earlier. No published RCT shows combinat=
ion protocols beat oral precursor alone.
Stacking with sirtuin activators (resveratrol, pterostilbene). Common in co=
mmercial products, often with weak human data. The story =E2=80=94 that you=
 need NAD+ as fuel for sirtuins, so giving both raises sirtuin activity mor=
e than either alone =E2=80=94 sounds reasonable but isn=E2=80=99t well-supp=
orted in trials.
Where The Research Points
For studies where subQ NAD+ didn=E2=80=99t produce clear functional outcome=
s: the literature backs oral NMN or NR at clinically tested doses (500-1000=
 mg/day) for at least 12 weeks as the more evidence-supported path. The mec=
hanism is more solid. The trial data is stronger.
For research models where NR didn=E2=80=99t show obvious benefit: switching=
 to NMN probably won=E2=80=99t change much, but the 2025 Christen et al. da=
ta does point to some difference in short-term kinetics. Honest answer: for=
 most populations they=E2=80=99re interchangeable.
For research models where both NR and NMN at adequate doses for adequate du=
ration didn=E2=80=99t produce functional benefit: the question probably isn=
=E2=80=99t =E2=80=9Cwhich precursor=E2=80=9D but =E2=80=9Cdoes raising NAD+=
 even matter in this model.=E2=80=9D Younger subjects with already-high NAD=
+ aren=E2=80=99t likely to see big effects. Older subjects, sedentary popul=
ations, or those with metabolic dysfunction are more likely to show measura=
ble changes =E2=80=94 which is exactly what trial subgroups tend to confirm=
=2E
For evidence depth: NR has the longest track record. For being one step clo=
ser to NAD+ in the pathway, with the caveat of a noisier regulatory history=
: NMN. They mostly converge.
Product Suggestions
Here are some good suggestions from products off Amazon.
NR:
Option 1 [ https://substack.com/redirect/cc11084b-8946-4ee1-92cb-88a534bd11=
70?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
Option 2 [ https://substack.com/redirect/0d8335b6-57e8-4ebe-b292-16d87ad30d=
ef?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
Option 3 [ https://substack.com/redirect/d710ce76-fa4b-48ea-b1f5-5e3fe96095=
a3?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
NMN:
Option 1 [ https://substack.com/redirect/6d413a2b-66dc-4455-92f0-fcd4dc9c70=
46?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
Option 2 [ https://substack.com/redirect/ad37a6ad-ddaa-4590-a329-fb803e76c2=
b8?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
Option 3 [ https://substack.com/redirect/8bcd6fc0-d8d8-4cac-bde6-ce7a009549=
fb?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
Things Worth Researching Further
The Christen et al. 2025 paper [ https://substack.com/redirect/633714cd-402=
f-41e0-81a0-1b8a748e0c8f?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy=
3p768BWtuZifRB-Zs ] in Nature Metabolism for the head-to-head NR/NMN/Nam co=
mparison and the gut microbiome angle. The original NMN paper from Sinclair=
=E2=80=99s lab (2013) and the follow-up mouse aging work. Charles Brenner=
=E2=80=99s writing on NAD+ biology and his criticism of NAD+ administration=
 outside the cell. Eric Verdin=E2=80=99s public talks on NAD+ delivery form=
ats. The 2023 twin study on NR =E2=80=94 useful for understanding what NR d=
oesn=E2=80=99t do as much as what it does. The MIB-626 trials for NMN in cl=
inical populations. The September 2025 FDA reversal on NMN supplement statu=
s for the regulatory backstory.
Final Thoughts
NAD+ biology is real. The decline with age is real. The case for restoring =
it through precursors is reasonable. What=E2=80=99s muddied the picture is =
a delivery format =E2=80=94 subQ NAD+ =E2=80=94 that probably doesn=E2=80=
=99t do what it claims, casting doubt on the whole thesis.
If your read on NAD+ from the subQ literature has been =E2=80=9Cthis whole =
space is hype=E2=80=9D =E2=80=94 the better read is that the wrong tool was=
 being tested. The oral precursors have stronger mechanism, better trial da=
ta, and more predictable outcomes. They also don=E2=80=99t produce a big su=
bjective effect, which is exactly what you=E2=80=99d expect given how they =
actually work.
NMN and NR aren=E2=80=99t dramatic compounds. They=E2=80=99re slow, structu=
ral tools that move things you can measure but rarely feel. That=E2=80=99s =
the point. The compounds that produce the strongest felt effects are usuall=
y the ones with the shortest lasting benefit. Mitophagy inducers, NAD+ prec=
ursors, mitochondrial biogenesis tools =E2=80=94 they all share this profil=
e.
Whether raising NAD+ for years translates into real longevity outcomes in h=
umans is a question the next decade of trials will answer. The mechanisms, =
the safety data, and the short-term biomarker improvements are already enou=
gh to make NMN and NR worth understanding deeply =E2=80=94 even if the subQ=
 NAD+ literature has been a letdown.
This is for research and educational purposes only. Nothing in this post is=
 medical advice, and this isn=E2=80=99t a recommendation to use NMN, NR, or=
 any NAD+ format personally. If the topic is of interest for any non-resear=
ch reason, that=E2=80=99s a conversation for a qualified medical profession=
al.
Drop questions below =E2=80=94 happy to go deeper on mechanism, the subQ de=
bate, dosing literature, or any other angle.
References
Head-to-head comparison of NAD+ precursors (2025): Christen S, Cuenoud B, e=
t al. Comparative effects of NR, NMN, and nicotinamide on NAD+ metabolism i=
n humans. Nature Metabolism. 2025. Link [ https://substack.com/redirect/633=
714cd-402f-41e0-81a0-1b8a748e0c8f?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdam=
Y0krRXGMy3p768BWtuZifRB-Zs ]
NR pharmacokinetics in humans: Trammell SAJ, Schmidt MS, Weidemann BJ, et a=
l. Nicotinamide riboside is uniquely and orally bioavailable in mice and hu=
mans. Nature Communications. 2016;7:12948. Link [ https://substack.com/redi=
rect/06eaff85-45e0-47dd-bd5a-3fe540e724f1?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ8=
5v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
NMN safety in healthy older men (250 mg/day): Igarashi M, Nakagawa-Nagahama=
 Y, Miura M, et al. Chronic nicotinamide mononucleotide supplementation ele=
vates blood nicotinamide adenine dinucleotide levels and alters muscle func=
tion in healthy older men. NPJ Aging. 2022;8(1):5. Link [ https://substack.=
com/redirect/3d9cbbc4-9f70-4fc8-9458-c7a1d29192d0?j=3DeyJ1IjoiNGl3b2U2In0.s=
VDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
NMN single-dose safety in healthy men: Irie J, Inagaki E, Fujita M, et al. =
Effect of oral administration of nicotinamide mononucleotide on clinical pa=
rameters and nicotinamide metabolite levels in healthy Japanese men. Endocr=
ine Journal. 2020;67(2):153-160.
NMN oral administration efficacy review: Yoshino M, Yoshino J, et al. Oral =
Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Incre=
ases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. Li=
nk [ https://substack.com/redirect/c98fc7de-febc-40f9-8a37-9d08ed19bcf6?j=
=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
NR twin study (5 months, escalating dose): Lapatto HAK, Kuusela M, Heikkine=
n A, et al. Nicotinamide riboside improves muscle mitochondrial biogenesis,=
 satellite cell differentiation, and gut microbiota in a twin study. Scienc=
e Advances. 2023;9(2):eadd5163. Link [ https://substack.com/redirect/d56638=
f0-43c9-4875-bf16-e204cbc9aed7?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0k=
rRXGMy3p768BWtuZifRB-Zs ]
NMN clinical trials updated review: The Safety and Antiaging Effects of Nic=
otinamide Mononucleotide in Human Clinical Trials: an Update. Link [ https:=
//substack.com/redirect/1ca34b90-20b4-4114-80fe-f329798630d2?j=3DeyJ1IjoiNG=
l3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
NMN metabolic variability and uptake pathways: Nicotinamide Mononucleotide =
Supplementation: Understanding Metabolic Variability and Clinical Implicati=
ons. Link [ https://substack.com/redirect/db89ba87-ec2f-42f8-abcf-8e5830fc6=
9a6?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
MIB-626 NMN in hospitalized patients: Oral MIB-626 (=CE=B2 Nicotinamide Mon=
onucleotide) Safely Raises Blood Nicotinamide Adenine Dinucleotide Levels i=
n Hospitalized Patients With COVID-19 and Acute Kidney Injury. 2025.
NR muscle and bone function trial (Mayo Clinic, NCT03818802): Link [ https:=
//substack.com/redirect/9737018a-4061-459d-b557-f2b4b2758ccc?j=3DeyJ1IjoiNG=
l3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
NR functional capacity in older veterans (NCT04691986): Link [ https://subs=
tack.com/redirect/a1083f0f-ad4f-476d-b711-078d0b8eda66?j=3DeyJ1IjoiNGl3b2U2=
In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
FDA NMN dietary supplement reversal (September 2025): FDA letters to NMN in=
gredient suppliers, September 29 and December 2, 2025. NPA [ https://substa=
ck.com/redirect/dc4cb2d0-d7e4-453f-84a6-168130522dde?j=3DeyJ1IjoiNGl3b2U2In=
0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ] | NutraIngredients [ https:=
//substack.com/redirect/452ce012-978e-4e44-9290-53568f668351?j=3DeyJ1IjoiNG=
l3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ]
=E2=80=94 Derek

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ext-transform: uppercase;letter-spacing: .2px;text-decoration: none" href=
=3D"https://substack.com/@dereksresearchradar">Derek</a></div></td></tr></t=
body></table></td></tr><tr><td><table role=3D"presentation" width=3D"auto" =
border=3D"0" cellspacing=3D"0" cellpadding=3D"0"><tbody><tr><td style=3D"ve=
rtical-align:middle;"><div class=3D"pencraft pc-reset color-secondary-ls1g8=
s line-height-20-t4M0El font-meta-MWBumP size-11-NuY2Zx weight-medium-fw81n=
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t-transform: uppercase;letter-spacing: .2px;"><time datetime=3D"2026-05-11T=
14:07:04.532Z">May 11</time></div></td></tr></tbody></table></td></tr></tbo=
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tion: none;">Upgrade to paid</span></a></div></div><div style=3D"font-size:=
 16px;line-height: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height: 1p=
x;background: rgb(0,0,0,.1);border: none;"></div><h2 class=3D"header-anchor=
-post" style=3D"position: relative;font-family: 'SF Pro Display',-apple-sys=
tem-headline,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto,H=
elvetica,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI Sy=
mbol';font-weight: bold;-webkit-font-smoothing: antialiased;-moz-osx-font-s=
moothing: antialiased;-webkit-appearance: optimizelegibility;-moz-appearanc=
e: optimizelegibility;appearance: optimizelegibility;margin: 1em 0 0.625em =
0;color: rgb(54,55,55);line-height: 1.16em;font-size: calc(1.625em * 1);">T=
he Landscape</h2><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-h=
eight: 26px;font-size: 16px;">The NAD+ conversation has gotten messy. IV NA=
D+. SubQ NAD+. NMN. NR. NA. NAM. Every podcast names a different &#8220;bes=
t&#8221; precursor.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);=
line-height: 26px;font-size: 16px;">A lot of researchers have looked at NAD=
+ protocols &#8212; usually subQ, sometimes IV &#8212; and walked away unim=
pressed by the data. Small effects, often nothing you can clearly tie back =
to the protocol. Then they read about NMN or NR and wonder if the field pic=
ked the wrong format from the start.</p><p style=3D"margin: 0 0 20px 0;colo=
r: rgb(54,55,55);line-height: 26px;font-size: 16px;">That confusion isn&#82=
17;t on the researcher. The NAD+ space has three real debates running at th=
e same time:</p><ol style=3D"margin-top: 0;padding: 0;"><li style=3D"margin=
: 8px 0 0 32px;"><p style=3D"color: rgb(54,55,55);line-height: 26px;margin-=
bottom: 0;box-sizing: border-box;padding-left: 4px;font-size: 16px;margin: =
0;">Does direct NAD+ administration even work, or does the molecule get bro=
ken down before it can do anything useful inside cells?</p></li><li style=
=3D"margin: 8px 0 0 32px;"><p style=3D"color: rgb(54,55,55);line-height: 26=
px;margin-bottom: 0;box-sizing: border-box;padding-left: 4px;font-size: 16p=
x;margin: 0;">Between NMN and NR, is there a real difference, or are they b=
asically the same?</p></li><li style=3D"margin: 8px 0 0 32px;"><p style=3D"=
color: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box-sizing: border-=
box;padding-left: 4px;font-size: 16px;margin: 0;">What dose, how long, and =
what outcomes are realistic?</p></li></ol><p style=3D"margin: 0 0 20px 0;co=
lor: rgb(54,55,55);line-height: 26px;font-size: 16px;">This post walks thro=
ugh all three.</p><div style=3D"font-size: 16px;line-height: 26px;"><hr sty=
le=3D"margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,0,.1);borde=
r: none;"></div><h2 class=3D"header-anchor-post" style=3D"position: relativ=
e;font-family: 'SF Pro Display',-apple-system-headline,system-ui,-apple-sys=
tem,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit-f=
ont-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit-app=
earance: optimizelegibility;-moz-appearance: optimizelegibility;appearance:=
 optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);line-heigh=
t: 1.16em;font-size: calc(1.625em * 1);">NAD+ Biology In One Page</h2><p st=
yle=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size:=
 16px;">NAD+ (nicotinamide adenine dinucleotide) is a helper molecule used =
in almost every metabolic process &#8212; ATP production, DNA repair, sirtu=
in activity, PARP activity, mitochondrial function. It exists in every cell=
, and cells contain far more NAD+ than they do its precursors.</p><p style=
=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16=
px;">NAD+ levels drop with age. That drop tracks with mitochondrial dysfunc=
tion, more DNA damage, lower sirtuin activity, and most of the hallmarks of=
 aging. Whether the drop is the cause or just a symptom is debated, but the=
 link is solid.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line=
-height: 26px;font-size: 16px;">You don&#8217;t get NAD+ directly from food=
 in any real amount. The body builds NAD+ from precursors through a few dif=
ferent pathways:</p><ul style=3D"margin-top: 0;padding: 0;"><li style=3D"ma=
rgin: 8px 0 0 32px;mso-special-format: bullet;"><p style=3D"color: rgb(54,5=
5,55);line-height: 26px;margin-bottom: 0;box-sizing: border-box;padding-lef=
t: 4px;font-size: 16px;margin: 0;"><strong>Tryptophan</strong><span> (de no=
vo pathway) &#8212; slow, inefficient</span></p></li><li style=3D"margin: 8=
px 0 0 32px;mso-special-format: bullet;"><p style=3D"color: rgb(54,55,55);l=
ine-height: 26px;margin-bottom: 0;box-sizing: border-box;padding-left: 4px;=
font-size: 16px;margin: 0;"><strong>NA / nicotinic acid</strong><span> (Pre=
iss-Handler pathway) &#8212; causes flushing, well-studied</span></p></li><=
li style=3D"margin: 8px 0 0 32px;mso-special-format: bullet;"><p style=3D"c=
olor: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box-sizing: border-b=
ox;padding-left: 4px;font-size: 16px;margin: 0;"><strong>NAM / nicotinamide=
</strong><span> (salvage pathway) &#8212; the main recycling route</span></=
p></li><li style=3D"margin: 8px 0 0 32px;mso-special-format: bullet;"><p st=
yle=3D"color: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box-sizing: =
border-box;padding-left: 4px;font-size: 16px;margin: 0;"><strong>NR / nicot=
inamide riboside</strong><span> &#8212; joins the salvage pathway one step =
further along</span></p></li><li style=3D"margin: 8px 0 0 32px;mso-special-=
format: bullet;"><p style=3D"color: rgb(54,55,55);line-height: 26px;margin-=
bottom: 0;box-sizing: border-box;padding-left: 4px;font-size: 16px;margin: =
0;"><strong>NMN / nicotinamide mononucleotide</strong><span> &#8212; one st=
ep closer to NAD+ than NR</span></p></li></ul><p style=3D"margin: 0 0 20px =
0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">The supplement w=
orld mostly lives in the last two. Everything else is either old news (niac=
in) or impractical (tryptophan loading).</p><div style=3D"font-size: 16px;l=
ine-height: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height: 1px;backg=
round: rgb(0,0,0,.1);border: none;"></div><h2 class=3D"header-anchor-post" =
style=3D"position: relative;font-family: 'SF Pro Display',-apple-system-hea=
dline,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetic=
a,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI Symbol';f=
ont-weight: bold;-webkit-font-smoothing: antialiased;-moz-osx-font-smoothin=
g: antialiased;-webkit-appearance: optimizelegibility;-moz-appearance: opti=
mizelegibility;appearance: optimizelegibility;margin: 1em 0 0.625em 0;color=
: rgb(54,55,55);line-height: 1.16em;font-size: calc(1.625em * 1);">The SubQ=
 NAD+ Debate</h2><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-h=
eight: 26px;font-size: 16px;">This is the elephant in the room, and it&#821=
7;s why a lot of researchers feel the broader NAD+ story isn&#8217;t delive=
ring.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 2=
6px;font-size: 16px;">The pro-subQ argument is simple: oral NAD+ has terrib=
le bioavailability (often cited at 2-10%), so the logic goes &#8212; skip t=
he gut, put it directly into the bloodstream, and it should work better. Su=
bQ NAD+ administration has become popular at longevity clinics because it&#=
8217;s more practical than IV but supposedly delivers more than oral.</p><p=
 style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-si=
ze: 16px;">The skeptical argument is about mechanism. NAD+ is a big, charge=
d molecule. Cells don&#8217;t have a known door (transporter) that lets a c=
irculating NAD+ molecule walk into a muscle cell or neuron and start workin=
g as a coenzyme. The body builds its NAD+ pool inside cells from precursors=
=2E It doesn&#8217;t import NAD+ from=20=
outside.</p><p style=3D"margin: 0 0 20p=
x 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">Eric Verdin, P=
resident of the Buck Institute for Research on Aging, has been the loudest =
voice on this. His position: when you administer NAD+ subQ or IV, most of i=
t gets broken down to nicotinamide before it ever reaches cells. The end re=
sult inside cells is basically the same as if you&#8217;d just taken nicoti=
namide orally. Charles Brenner (the researcher who first identified NR as a=
n NAD+ precursor) has been even blunter &#8212; he&#8217;s called NAD+ admi=
nistration outside the cell mechanistically incoherent.</p><p style=3D"marg=
in: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">So =
what does that mean for the research showing modest or no benefit from subQ=
 NAD+? Two fair reads:</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,5=
5);line-height: 26px;font-size: 16px;">The molecule gets chopped up into ni=
cotinamide and the rest of the NAD+ structure within minutes of administrat=
ion. What actually raises cellular NAD+ is just nicotinamide &#8212; same a=
s a B3 vitamin. Plausible. Fits the biochemistry.</p><p style=3D"margin: 0 =
0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">Or: it br=
iefly raises NAD+ in the blood, but tissue NAD+ &#8212; which is what actua=
lly matters &#8212; barely moves because cells make their own and don&#8217=
;t need imported NAD+.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,5=
5);line-height: 26px;font-size: 16px;">Either way, the end result is the sa=
me: subQ NAD+ may be functioning as nicotinamide administration. And as the=
 next section covers, nicotinamide is the weakest of the precursors for kee=
ping NAD+ high over time.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,5=
5,55);line-height: 26px;font-size: 16px;">This is the key context for anyon=
e reading the NAD+ literature. Weak results from subQ NAD+ research aren&#8=
217;t evidence that NAD+ doesn&#8217;t matter. They&#8217;re evidence that =
the delivery format probably isn&#8217;t doing what the marketing claims.</=
p><div style=3D"font-size: 16px;line-height: 26px;"><hr style=3D"margin: 32=
px 0;padding: 0;height: 1px;background: rgb(0,0,0,.1);border: none;"></div>=
<h2 class=3D"header-anchor-post" style=3D"position: relative;font-family: '=
SF Pro Display',-apple-system-headline,system-ui,-apple-system,BlinkMacSyst=
emFont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple Color Emoji','Se=
goe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit-font-smoothing: a=
ntialiased;-moz-osx-font-smoothing: antialiased;-webkit-appearance: optimiz=
elegibility;-moz-appearance: optimizelegibility;appearance: optimizelegibil=
ity;margin: 1em 0 0.625em 0;color: rgb(54,55,55);line-height: 1.16em;font-s=
ize: calc(1.625em * 1);">NMN vs NR &#8212; What They Actually Are</h2><p st=
yle=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size:=
 16px;"><strong>NR (nicotinamide riboside)</strong><span> is nicotinamide a=
ttached to a ribose sugar. Discovered as an NAD+ precursor by Charles Brenn=
er&#8217;s lab in 2004. Patented and sold by ChromaDex under the Niagen bra=
nd. The most studied NAD+ precursor in humans by trial count.</span></p><p =
style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-siz=
e: 16px;"><strong>NMN (nicotinamide mononucleotide)</strong><span> is NR wi=
th a phosphate group added. One enzymatic step closer to NAD+ in the pathwa=
y. Closely tied to David Sinclair&#8217;s lab at Harvard, which published t=
he landmark 2013 paper showing NMN reversed multiple aging markers in mice.=
</span></p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height:=
 26px;font-size: 16px;"><span>The two are more similar than different. For =
years there was a debate about whether NMN gets absorbed whole (through a g=
ut transporter called Slc12a8) or first gets stripped down to NR in the gut=
 and then taken up. The 2025 Christen et al. study in </span><em>Nature Met=
abolism</em><span> mostly settled it: NMN&#8217;s path through nicotinamide=
 and then nicotinic acid looked a lot like NR&#8217;s, and both changed gut=
 bacteria in similar ways.</span></p><p style=3D"margin: 0 0 20px 0;color: =
rgb(54,55,55);line-height: 26px;font-size: 16px;">Practically: NMN and NR a=
ren&#8217;t fundamentally different molecules. They feed into the same path=
way, raise NAD+ to similar levels at similar doses, and have overlapping (b=
ut not identical) downstream effects.</p><p style=3D"margin: 0 0 20px 0;col=
or: rgb(54,55,55);line-height: 26px;font-size: 16px;">The differences that =
do matter:</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-heig=
ht: 26px;font-size: 16px;"><strong>Stability and delivery.</strong><span> N=
MN holds up better in water. NR holds up better as a chloride salt in capsu=
les. Both come in solid oral capsule forms now.</span></p><p style=3D"margi=
n: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><str=
ong>Regulatory status.</strong><span> NR has been an established dietary su=
pplement in the US for years. NMN had a rougher path &#8212; the FDA pulled=
 it from the supplement category in November 2022 over the drug preclusion =
clause (MetroBiotech&#8217;s MIB-626 was in drug development). After a mult=
i-year fight led by the Natural Products Association, the FDA reversed itse=
lf on September 29, 2025, confirming NMN is lawful as a dietary supplement.=
 As of late 2025, NMN is back on Amazon and standard retail.</span></p><p s=
tyle=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size=
: 16px;"><strong>Evidence depth.</strong><span> NR has a longer track recor=
d of human trials. NMN&#8217;s evidence base is catching up fast &#8212; as=
 of mid-2025, at least five NMN RCTs and ten NR RCTs have reported metaboli=
c outcomes, with more on the way.</span></p><div style=3D"font-size: 16px;l=
ine-height: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height: 1px;backg=
round: rgb(0,0,0,.1);border: none;"></div><h2 class=3D"header-anchor-post" =
style=3D"position: relative;font-family: 'SF Pro Display',-apple-system-hea=
dline,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetic=
a,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI Symbol';f=
ont-weight: bold;-webkit-font-smoothing: antialiased;-moz-osx-font-smoothin=
g: antialiased;-webkit-appearance: optimizelegibility;-moz-appearance: opti=
mizelegibility;appearance: optimizelegibility;margin: 1em 0 0.625em 0;color=
: rgb(54,55,55);line-height: 1.16em;font-size: calc(1.625em * 1);">What The=
 Human Data Shows</h2><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);l=
ine-height: 26px;font-size: 16px;">This is where the picture sharpens. We&#=
8217;re not just looking at rodents anymore.</p><p style=3D"margin: 0 0 20p=
x 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><strong>The he=
ad-to-head trial (Christen et al., 2025, </strong><em><strong>Nature Metabo=
lism</strong></em><strong>).</strong><span> The first direct human comparis=
on of NR, NMN, and nicotinamide. NR and NMN both roughly doubled blood NAD+=
 over 14 days. Nicotinamide didn&#8217;t. Short-term, nicotinamide raised N=
AD+ faster, but the effect didn&#8217;t last. The conclusion: NR and NMN ar=
e comparable for keeping NAD+ elevated long-term. Nicotinamide isn&#8217;t =
a good pick for sustained elevation.</span></p><p style=3D"margin: 0 0 20px=
 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><strong>NR huma=
n trials (overall).</strong><span> Across multiple placebo-controlled trial=
s at doses from 100 mg to 2000 mg/day, NR reliably raises whole-blood NAD+,=
 is well-tolerated, and has shown some improvements in muscle acetylcarniti=
ne levels, arterial stiffness, blood pressure, and inflammatory markers. Ho=
nest summary: NAD+ goes up, safety is clean, functional outcomes are hit-or=
-miss. The twin study (Lapatto et al., 2023) used escalating NR doses of 25=
0 to 1000 mg/day for 5 months in BMI-discordant identical twins. It showed =
improved muscle mitochondrial numbers, better myoblast differentiation, and=
 changes in gut microbiota &#8212; but no real improvement in body fat or m=
etabolic health.</span></p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,=
55);line-height: 26px;font-size: 16px;"><strong>NMN human trials.</strong><=
span> The 250 mg/day Japanese trial in older men (Igarashi et al., 2022) sh=
owed measurable NAD+ elevation and &#8220;nominally significant&#8221; impr=
ovements in muscle function over 6-12 weeks. The MIB-626 trial in hospitali=
zed COVID-19 patients with acute kidney injury (2 g/day for 14 days) showed=
 safe NAD+ elevation in a clinical setting. More recent NMN trials have rep=
orted improvements in sleep quality, walking speed in older adults, insulin=
 sensitivity, and exercise performance.</span></p><p style=3D"margin: 0 0 2=
0px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><strong>Wher=
e both come up short.</strong><span> Neither NMN nor NR has been shown to e=
xtend human lifespan, prevent specific age-related diseases, or reverse agi=
ng in any meaningful way. The trials are short (usually 8-12 weeks, longest=
 around 5-6 months), small (median around 40 people), and mostly in healthy=
 populations where there isn&#8217;t much room to improve. What the trials =
do show consistently: NAD+ goes up with both, safety is good at doses up to=
 2 g/day, and downstream effects are real but modest.</span></p><p style=3D=
"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;=
">The honest takeaway from the literature: a big chunk of the disappointmen=
t in NAD+ outcomes probably comes down to the wrong precursor (oral nicotin=
amide alone isn&#8217;t great), the wrong delivery format (subQ NAD+ may no=
t actually do what the marketing claims), or expecting too much of a &#8220=
;feel&#8221; from raising NAD+ in the first place.</p><div style=3D"font-si=
ze: 16px;line-height: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height:=
 1px;background: rgb(0,0,0,.1);border: none;"></div><h2 class=3D"header-anc=
hor-post" style=3D"position: relative;font-family: 'SF Pro Display',-apple-=
system-headline,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Robot=
o,Helvetica,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI=
 Symbol';font-weight: bold;-webkit-font-smoothing: antialiased;-moz-osx-fon=
t-smoothing: antialiased;-webkit-appearance: optimizelegibility;-moz-appear=
ance: optimizelegibility;appearance: optimizelegibility;margin: 1em 0 0.625=
em 0;color: rgb(54,55,55);line-height: 1.16em;font-size: calc(1.625em * 1);=
">Why NAD+ Interventions Don&#8217;t Feel Like Much</h2><p style=3D"margin:=
 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">Worth =
its own section because it trips up almost every read of the literature.</p=
><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font=
-size: 16px;">The marketing around NAD+ &#8212; especially IV and subQ &#82=
12; strongly implies an experience: energy, mental clarity, almost a stimul=
ant-like effect. Some user reports describe that. A lot don&#8217;t. Contro=
lled trials don&#8217;t even measure &#8220;feel&#8221; as a primary outcom=
e.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px=
;font-size: 16px;">Here&#8217;s the mechanism reason: NAD+ is a coenzyme. C=
oenzymes don&#8217;t usually produce a felt effect. They&#8217;re tools tha=
t enzymes use to run reactions in the background. Raising NAD+ by 50% doesn=
&#8217;t produce a sensation any more than raising cellular ATP would. Both=
 are necessary for cells to function. Neither is something you actually fee=
l.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px=
;font-size: 16px;">What trials do show with NMN or NR at adequate doses ove=
r months: better exercise tolerance, small gains in muscle endurance or str=
ength, better sleep in some subgroups, lower inflammation markers, lower ac=
ylcarnitines (mitochondria using fuel more efficiently), and sometimes bett=
er insulin sensitivity. None of these are dramatic. Most are measurable, no=
t noticeable.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-h=
eight: 26px;font-size: 16px;">If NAD+ protocols are being judged against a =
stimulant-like response, they&#8217;ll look disappointing no matter the for=
mat. That&#8217;s not the protocol failing. That&#8217;s the marketing sett=
ing bad expectations.</p><div style=3D"font-size: 16px;line-height: 26px;">=
<hr style=3D"margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,0,.1=
);border: none;"></div><h2 class=3D"header-anchor-post" style=3D"position: =
relative;font-family: 'SF Pro Display',-apple-system-headline,system-ui,-ap=
ple-system,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,=
'Apple Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-w=
ebkit-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-web=
kit-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appe=
arance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);lin=
e-height: 1.16em;font-size: calc(1.625em * 1);">Dosing Patterns From The Li=
terature</h2><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-heigh=
t: 26px;font-size: 16px;">What the trials have actually used &#8212; not wh=
at supplement companies recommend.</p><p style=3D"margin: 0 0 20px 0;color:=
 rgb(54,55,55);line-height: 26px;font-size: 16px;"><strong>NR.</strong><spa=
n> Single-dose pharmacokinetics tested at 100, 300, and 1000 mg, with dose-=
dependent increases in blood NAD+. Long-term dosing trials have used 250 mg=
 up to 2000 mg/day. 1000 mg/day (usually 500 mg twice a day) is the most-st=
udied dose with functional results. Time to measurable NAD+ rise: days. Tim=
e to functional effects: 8-12 weeks at minimum.</span></p><p style=3D"margi=
n: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><str=
ong>NMN.</strong><span> Single-dose safety established at 100, 250, and 500=
 mg in healthy Japanese men. Long-term trials have used 250 mg/day to 1250 =
mg/day for 4-12 weeks. 500-1000 mg/day is where most positive results come =
from. The 250 mg/day older-men trial showed effects but smaller ones. Time =
course is similar to NR &#8212; NAD+ rises in days, functional changes show=
 up at 6-12 weeks and beyond.</span></p><p style=3D"margin: 0 0 20px 0;colo=
r: rgb(54,55,55);line-height: 26px;font-size: 16px;"><strong>Timing.</stron=
g><span> Both NMN and NR have been used with and without food in trials. Fo=
od doesn&#8217;t really get in the way of absorption. Morning dosing is the=
 convention but not based on evidence.</span></p><p style=3D"margin: 0 0 20=
px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><strong>Combi=
nation protocols.</strong><span> Some longevity clinics use subQ NAD+ as a =
&#8220;loading&#8221; phase and then oral NMN or NR for maintenance. The re=
asoning is shaky for the reasons covered earlier. No published RCT shows co=
mbination protocols beat oral precursor alone.</span></p><p style=3D"margin=
: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><stro=
ng>Stacking with sirtuin activators</strong><span> (resveratrol, pterostilb=
ene). Common in commercial products, often with weak human data. The story =
&#8212; that you need NAD+ as fuel for sirtuins, so giving both raises sirt=
uin activity more than either alone &#8212; sounds reasonable but isn&#8217=
;t well-supported in trials.</span></p><div style=3D"font-size: 16px;line-h=
eight: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height: 1px;background=
: rgb(0,0,0,.1);border: none;"></div><h2 class=3D"header-anchor-post" style=
=3D"position: relative;font-family: 'SF Pro Display',-apple-system-headline=
,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetica,Ari=
al,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-w=
eight: bold;-webkit-font-smoothing: antialiased;-moz-osx-font-smoothing: an=
tialiased;-webkit-appearance: optimizelegibility;-moz-appearance: optimizel=
egibility;appearance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb=
(54,55,55);line-height: 1.16em;font-size: calc(1.625em * 1);">Where The Res=
earch Points</h2><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-h=
eight: 26px;font-size: 16px;">For studies where subQ NAD+ didn&#8217;t prod=
uce clear functional outcomes: the literature backs oral NMN or NR at clini=
cally tested doses (500-1000 mg/day) for at least 12 weeks as the more evid=
ence-supported path. The mechanism is more solid. The trial data is stronge=
r.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px=
;font-size: 16px;">For research models where NR didn&#8217;t show obvious b=
enefit: switching to NMN probably won&#8217;t change much, but the 2025 Chr=
isten et al. data does point to some difference in short-term kinetics. Hon=
est answer: for most populations they&#8217;re interchangeable.</p><p style=
=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16=
px;">For research models where both NR and NMN at adequate doses for adequa=
te duration didn&#8217;t produce functional benefit: the question probably =
isn&#8217;t &#8220;which precursor&#8221; but &#8220;does raising NAD+ even=
 matter in this model.&#8221; Younger subjects with already-high NAD+ aren&=
#8217;t likely to see big effects. Older subjects, sedentary populations, o=
r those with metabolic dysfunction are more likely to show measurable chang=
es &#8212; which is exactly what trial subgroups tend to confirm.</p><p sty=
le=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: =
16px;">For evidence depth: NR has the longest track record. For being one s=
tep closer to NAD+ in the pathway, with the caveat of a noisier regulatory =
history: NMN. They mostly converge.</p><div style=3D"font-size: 16px;line-h=
eight: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height: 1px;background=
: rgb(0,0,0,.1);border: none;"></div><h2 class=3D"header-anchor-post" style=
=3D"position: relative;font-family: 'SF Pro Display',-apple-system-headline=
,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetica,Ari=
al,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-w=
eight: bold;-webkit-font-smoothing: antialiased;-moz-osx-font-smoothing: an=
tialiased;-webkit-appearance: optimizelegibility;-moz-appearance: optimizel=
egibility;appearance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb=
(54,55,55);line-height: 1.16em;font-size: calc(1.625em * 1);">Product Sugge=
stions</h2><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height:=
 26px;font-size: 16px;">Here are some good suggestions from products off Am=
azon.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 2=
6px;font-size: 16px;"><strong>NR:</strong></p><ul style=3D"margin-top: 0;pa=
dding: 0;"><li style=3D"margin: 8px 0 0 32px;mso-special-format: bullet;"><=
p style=3D"color: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box-sizi=
ng: border-box;padding-left: 4px;font-size: 16px;margin: 0;"><a href=3D"htt=
ps://substack.com/redirect/cc11084b-8946-4ee1-92cb-88a534bd1170?j=3DeyJ1Ijo=
iNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" style=3D"color: #=
ff6719;text-decoration: none;">Option 1</a></p></li><li style=3D"margin: 8p=
x 0 0 32px;mso-special-format: bullet;"><p style=3D"color: rgb(54,55,55);li=
ne-height: 26px;margin-bottom: 0;box-sizing: border-box;padding-left: 4px;f=
ont-size: 16px;margin: 0;"><a href=3D"https://substack.com/redirect/0d8335b=
6-57e8-4ebe-b292-16d87ad30def?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0kr=
RXGMy3p768BWtuZifRB-Zs" style=3D"color: #ff6719;text-decoration: none;">Opt=
ion 2</a></p></li><li style=3D"margin: 8px 0 0 32px;mso-special-format: bul=
let;"><p style=3D"color: rgb(54,55,55);line-height: 26px;margin-bottom: 0;b=
ox-sizing: border-box;padding-left: 4px;font-size: 16px;margin: 0;"><a href=
=3D"https://substack.com/redirect/d710ce76-fa4b-48ea-b1f5-5e3fe96095a3?j=3D=
eyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" style=3D"c=
olor: #ff6719;text-decoration: none;">Option 3</a></p></li></ul><p style=3D=
"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;=
"><strong>NMN:</strong></p><ul style=3D"margin-top: 0;padding: 0;"><li styl=
e=3D"margin: 8px 0 0 32px;mso-special-format: bullet;"><p style=3D"color: r=
gb(54,55,55);line-height: 26px;margin-bottom: 0;box-sizing: border-box;padd=
ing-left: 4px;font-size: 16px;margin: 0;"><a href=3D"https://substack.com/r=
edirect/6d413a2b-66dc-4455-92f0-fcd4dc9c7046?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRt=
mZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" style=3D"color: #ff6719;text-decorat=
ion: none;">Option 1</a></p></li><li style=3D"margin: 8px 0 0 32px;mso-spec=
ial-format: bullet;"><p style=3D"color: rgb(54,55,55);line-height: 26px;mar=
gin-bottom: 0;box-sizing: border-box;padding-left: 4px;font-size: 16px;marg=
in: 0;"><a href=3D"https://substack.com/redirect/ad37a6ad-ddaa-4590-a329-fb=
803e76c2b8?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB=
-Zs" style=3D"color: #ff6719;text-decoration: none;">Option 2</a></p></li><=
li style=3D"margin: 8px 0 0 32px;mso-special-format: bullet;"><p style=3D"c=
olor: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box-sizing: border-b=
ox;padding-left: 4px;font-size: 16px;margin: 0;"><a href=3D"https://substac=
k.com/redirect/8bcd6fc0-d8d8-4cac-bde6-ce7a009549fb?j=3DeyJ1IjoiNGl3b2U2In0=
=2EsVDxRtmZ85v8kfdamY0krRXGMy3p768BWtu=
ZifRB-Zs" style=3D"color: #ff6719;text-=
decoration: none;">Option 3</a></p></li></ul><div style=3D"font-size: 16px;=
line-height: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height: 1px;back=
ground: rgb(0,0,0,.1);border: none;"></div><h2 class=3D"header-anchor-post"=
 style=3D"position: relative;font-family: 'SF Pro Display',-apple-system-he=
adline,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto,Helveti=
ca,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI Symbol';=
font-weight: bold;-webkit-font-smoothing: antialiased;-moz-osx-font-smoothi=
ng: antialiased;-webkit-appearance: optimizelegibility;-moz-appearance: opt=
imizelegibility;appearance: optimizelegibility;margin: 1em 0 0.625em 0;colo=
r: rgb(54,55,55);line-height: 1.16em;font-size: calc(1.625em * 1);">Things =
Worth Researching Further</h2><p style=3D"margin: 0 0 20px 0;color: rgb(54,=
55,55);line-height: 26px;font-size: 16px;"><span>The </span><a href=3D"http=
s://substack.com/redirect/633714cd-402f-41e0-81a0-1b8a748e0c8f?j=3DeyJ1Ijoi=
NGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" style=3D"color: #f=
f6719;text-decoration: none;">Christen et al. 2025 paper</a><span> in </spa=
n><em>Nature Metabolism</em><span> for the head-to-head NR/NMN/Nam comparis=
on and the gut microbiome angle. The original NMN paper from Sinclair&#8217=
;s lab (2013) and the follow-up mouse aging work. Charles Brenner&#8217;s w=
riting on NAD+ biology and his criticism of NAD+ administration outside the=
 cell. Eric Verdin&#8217;s public talks on NAD+ delivery formats. The 2023 =
twin study on NR &#8212; useful for understanding what NR doesn&#8217;t do =
as much as what it does. The MIB-626 trials for NMN in clinical populations=
=2E The September 2025 FDA reversal on=20=
NMN supplement status for the regulato=
ry backstory.</span></p><div style=3D"font-size: 16px;line-height: 26px;"><=
hr style=3D"margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,0,.1)=
;border: none;"></div><h2 class=3D"header-anchor-post" style=3D"position: r=
elative;font-family: 'SF Pro Display',-apple-system-headline,system-ui,-app=
le-system,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'=
Apple Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-we=
bkit-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webk=
it-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);line=
-height: 1.16em;font-size: calc(1.625em * 1);">Final Thoughts</h2><p style=
=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16=
px;">NAD+ biology is real. The decline with age is real. The case for resto=
ring it through precursors is reasonable. What&#8217;s muddied the picture =
is a delivery format &#8212; subQ NAD+ &#8212; that probably doesn&#8217;t =
do what it claims, casting doubt on the whole thesis.</p><p style=3D"margin=
: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">If yo=
ur read on NAD+ from the subQ literature has been &#8220;this whole space i=
s hype&#8221; &#8212; the better read is that the wrong tool was being test=
ed. The oral precursors have stronger mechanism, better trial data, and mor=
e predictable outcomes. They also don&#8217;t produce a big subjective effe=
ct, which is exactly what you&#8217;d expect given how they actually work.<=
/p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;fo=
nt-size: 16px;">NMN and NR aren&#8217;t dramatic compounds. They&#8217;re s=
low, structural tools that move things you can measure but rarely feel. Tha=
t&#8217;s the point. The compounds that produce the strongest felt effects =
are usually the ones with the shortest lasting benefit. Mitophagy inducers,=
 NAD+ precursors, mitochondrial biogenesis tools &#8212; they all share thi=
s profile.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-heig=
ht: 26px;font-size: 16px;">Whether raising NAD+ for years translates into r=
eal longevity outcomes in humans is a question the next decade of trials wi=
ll answer. The mechanisms, the safety data, and the short-term biomarker im=
provements are already enough to make NMN and NR worth understanding deeply=
 &#8212; even if the subQ NAD+ literature has been a letdown.</p><p style=
=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16=
px;"><em>This is for research and educational purposes only. Nothing in thi=
s post is medical advice, and this isn&#8217;t a recommendation to use NMN,=
 NR, or any NAD+ format personally. If the topic is of interest for any non=
-research reason, that&#8217;s a conversation for a qualified medical profe=
ssional.</em></p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-h=
eight: 26px;font-size: 16px;">Drop questions below &#8212; happy to go deep=
er on mechanism, the subQ debate, dosing literature, or any other angle.</p=
><div style=3D"font-size: 16px;line-height: 26px;"><hr style=3D"margin: 32p=
x 0;padding: 0;height: 1px;background: rgb(0,0,0,.1);border: none;"></div><=
h2 class=3D"header-anchor-post" style=3D"position: relative;font-family: 'S=
F Pro Display',-apple-system-headline,system-ui,-apple-system,BlinkMacSyste=
mFont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple Color Emoji','Seg=
oe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit-font-smoothing: an=
tialiased;-moz-osx-font-smoothing: antialiased;-webkit-appearance: optimize=
legibility;-moz-appearance: optimizelegibility;appearance: optimizelegibili=
ty;margin: 1em 0 0.625em 0;color: rgb(54,55,55);line-height: 1.16em;font-si=
ze: calc(1.625em * 1);">References</h2><p style=3D"margin: 0 0 20px 0;color=
: rgb(54,55,55);line-height: 26px;font-size: 16px;"><strong>Head-to-head co=
mparison of NAD+ precursors (2025):</strong><span> Christen S, Cuenoud B, e=
t al. Comparative effects of NR, NMN, and nicotinamide on NAD+ metabolism i=
n humans. </span><em>Nature Metabolism.</em><span> 2025. </span><a href=3D"=
https://substack.com/redirect/633714cd-402f-41e0-81a0-1b8a748e0c8f?j=3DeyJ1=
IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" style=3D"color=
: #ff6719;text-decoration: none;">Link</a></p><p style=3D"margin: 0 0 20px =
0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><strong>NR pharm=
acokinetics in humans:</strong><span> Trammell SAJ, Schmidt MS, Weidemann B=
J, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice=
 and humans. </span><em>Nature Communications.</em><span> 2016;7:12948. </s=
pan><a href=3D"https://substack.com/redirect/06eaff85-45e0-47dd-bd5a-3fe540=
e724f1?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs"=
 style=3D"color: #ff6719;text-decoration: none;">Link</a></p><p style=3D"ma=
rgin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><=
strong>NMN safety in healthy older men (250 mg/day):</strong><span> Igarash=
i M, Nakagawa-Nagahama Y, Miura M, et al. Chronic nicotinamide mononucleoti=
de supplementation elevates blood nicotinamide adenine dinucleotide levels =
and alters muscle function in healthy older men. </span><em>NPJ Aging.</em>=
<span> 2022;8(1):5. </span><a href=3D"https://substack.com/redirect/3d9cbbc=
4-9f70-4fc8-9458-c7a1d29192d0?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0kr=
RXGMy3p768BWtuZifRB-Zs" style=3D"color: #ff6719;text-decoration: none;">Lin=
k</a></p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 2=
6px;font-size: 16px;"><strong>NMN single-dose safety in healthy men:</stron=
g><span> Irie J, Inagaki E, Fujita M, et al. Effect of oral administration =
of nicotinamide mononucleotide on clinical parameters and nicotinamide meta=
bolite levels in healthy Japanese men. </span><em>Endocrine Journal.</em><s=
pan> 2020;67(2):153-160.</span></p><p style=3D"margin: 0 0 20px 0;color: rg=
b(54,55,55);line-height: 26px;font-size: 16px;"><strong>NMN oral administra=
tion efficacy review:</strong><span> Yoshino M, Yoshino J, et al. Oral Admi=
nistration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases=
 Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. </span=
><a href=3D"https://substack.com/redirect/c98fc7de-febc-40f9-8a37-9d08ed19b=
cf6?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" st=
yle=3D"color: #ff6719;text-decoration: none;">Link</a></p><p style=3D"margi=
n: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;"><str=
ong>NR twin study (5 months, escalating dose):</strong><span> Lapatto HAK, =
Kuusela M, Heikkinen A, et al. Nicotinamide riboside improves muscle mitoch=
ondrial biogenesis, satellite cell differentiation, and gut microbiota in a=
 twin study. </span><em>Science Advances.</em><span> 2023;9(2):eadd5163. </=
span><a href=3D"https://substack.com/redirect/d56638f0-43c9-4875-bf16-e204c=
bc9aed7?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs=
" style=3D"color: #ff6719;text-decoration: none;">Link</a></p><p style=3D"m=
argin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">=
<strong>NMN clinical trials updated review:</strong><span> The Safety and A=
ntiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: a=
n Update. </span><a href=3D"https://substack.com/redirect/1ca34b90-20b4-411=
4-80fe-f329798630d2?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768=
BWtuZifRB-Zs" style=3D"color: #ff6719;text-decoration: none;">Link</a></p><=
p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-s=
ize: 16px;"><strong>NMN metabolic variability and uptake pathways:</strong>=
<span> Nicotinamide Mononucleotide Supplementation: Understanding Metabolic=
 Variability and Clinical Implications. </span><a href=3D"https://substack.=
com/redirect/db89ba87-ec2f-42f8-abcf-8e5830fc69a6?j=3DeyJ1IjoiNGl3b2U2In0.s=
VDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" style=3D"color: #ff6719;text-de=
coration: none;">Link</a></p><p style=3D"margin: 0 0 20px 0;color: rgb(54,5=
5,55);line-height: 26px;font-size: 16px;"><strong>MIB-626 NMN in hospitaliz=
ed patients:</strong><span> Oral MIB-626 (&#946; Nicotinamide Mononucleotid=
e) Safely Raises Blood Nicotinamide Adenine Dinucleotide Levels in Hospital=
ized Patients With COVID-19 and Acute Kidney Injury. 2025.</span></p><p sty=
le=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: =
16px;"><strong>NR muscle and bone function trial (Mayo Clinic, NCT03818802)=
:</strong><span> </span><a href=3D"https://substack.com/redirect/9737018a-4=
061-459d-b557-f2b4b2758ccc?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXG=
My3p768BWtuZifRB-Zs" style=3D"color: #ff6719;text-decoration: none;">Link</=
a></p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px=
;font-size: 16px;"><strong>NR functional capacity in older veterans (NCT046=
91986):</strong><span> </span><a href=3D"https://substack.com/redirect/a108=
3f0f-ad4f-476d-b711-078d0b8eda66?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY=
0krRXGMy3p768BWtuZifRB-Zs" style=3D"color: #ff6719;text-decoration: none;">=
Link</a></p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height=
: 26px;font-size: 16px;"><strong>FDA NMN dietary supplement reversal (Septe=
mber 2025):</strong><span> FDA letters to NMN ingredient suppliers, Septemb=
er 29 and December 2, 2025. </span><a href=3D"https://substack.com/redirect=
/dc4cb2d0-d7e4-453f-84a6-168130522dde?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8k=
fdamY0krRXGMy3p768BWtuZifRB-Zs" style=3D"color: #ff6719;text-decoration: no=
ne;">NPA</a><span> | </span><a href=3D"https://substack.com/redirect/452ce0=
12-978e-4e44-9290-53568f668351?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0k=
rRXGMy3p768BWtuZifRB-Zs" style=3D"color: #ff6719;text-decoration: none;">Nu=
traIngredients</a></p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);l=
ine-height: 26px;font-size: 16px;">&#8212; Derek</p><div class=3D"subscribe=
-widget is-signed-up" data-component-name=3D"SubscribeWidget" style=3D"marg=
in: 0 0 1em;direction: ltr;font-size: 16px;line-height: 26px;margin-bottom:=
 0;"><div class=3D"pencraft pc-reset button-wrapper" style=3D"text-decorati=
on: unset;list-style: none;font-size: 16px;line-height: 26px;text-align: ce=
nter;cursor: pointer;border-radius: 4px;"><a class=3D"button subscribe-btn =
primary" href=3D"https://substack.com/redirect/2/eyJlIjoiaHR0cHM6Ly9kZXJla3=
BydXNraS5zdWJzdGFjay5jb20vc3Vic2NyaWJlP3V0bV9zb3VyY2U9cG9zdCZ1dG1fY2FtcGFpZ=
249ZW1haWwtY2hlY2tvdXQmbmV4dD1odHRwcyUzQSUyRiUyRmRlcmVrcHJ1c2tpLnN1YnN0YWNr=
LmNvbSUyRnAlMkZubW4tdnMtbnItYS1kZWVwLWRpdmUtZm9yLXJlc2VhcmNoZXJzJnI9NGl3b2U=
2JnRva2VuPWV5SjFjMlZ5WDJsa0lqb3lOek0yTWpJek9UZ3NJbWxoZENJNk1UYzNPRFV3T0RZMU=
9Dd2laWGh3SWpveE56Z3hNVEF3TmpVNExDSnBjM01pT2lKd2RXSXRNek0yTlRNMk55SXNJbk4xW=
WlJNkltTm9aV05yYjNWMEluMC5zMW5XbGRxZmFIWG81ZnVxb0lUZTlhTW40bnRHX25qV0RLYTEw=
Y05DTVhvIiwicCI6MTk3MjE5Mzg0LCJzIjozMzY1MzY3LCJmIjp0cnVlLCJ1IjoyNzM2MjIzOTg=
sImlhdCI6MTc3ODUwODY1OCwiZXhwIjoyMDk0MDg0NjU4LCJpc3MiOiJwdWItMCIsInN1YiI6Im=
xpbmstcmVkaXJlY3QifQ.VoZgEcFWumueelLDamGIcPzqlumqhfIiZ9LCOxv8BGc?&utm_mediu=
m=3Demail&utm_source=3Dsubscribe-widget&utm_content=3D197219384" style=3D"f=
ont-family: system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto,He=
lvetica,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI Sym=
bol';display: inline-block;box-sizing: border-box;cursor: pointer;border: n=
one;border-radius: 8px;font-size: 14px;line-height: 20px;font-weight: 600;t=
ext-align: center;opacity: 1;outline: none;white-space: nowrap;text-decorat=
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