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How NAD Precursors Work in the Body or what do I need to understand before taking a NAD supplement
Generated by ChatGPT (GPT-5 Thinking mini, OpenAI). Answer obtained August 10, 2025. Note: AI-generated content may contain inaccuracies; consult primary literature for clinical decisions.
Step 1 — Ingestion
• You swallow NR, NMN, or niacinamide.
• NAD⁺ itself is mostly broken down in the gut into smaller units before absorption.
Step 2 — Absorption
• NR: Taken up in the small intestine by nucleoside transporters.
• NMN: Likely broken down into NR before uptake in humans (still debated), though some evidence suggests a specific transporter exists in mice.
• Niacinamide: Readily absorbed via facilitated diffusion.
Step 3 — First-pass conversion
• In intestinal cells and liver, precursors enter the NAD salvage pathway:
• NR → NMN → NAD⁺
• NAM → NMN → NAD⁺
• Enzymes: NRK (nicotinamide riboside kinase) and NMNAT (nicotinamide mononucleotide adenylyltransferase) are key rate-limiting steps.
Step 4 — Distribution
• NAD⁺ made in the liver is not directly shipped out — instead, NAD precursors (like NAM) circulate and are taken up by other tissues to make their own NAD⁺.
Step 5 — Regulation & limits
• If intake is too high, excess NAM accumulates. This inhibits sirtuins and PARPs, counteracting benefits.
• Enzymes like CD38 constantly break down NAD⁺ — higher with age and inflammation, meaning older adults may “burn through” NAD⁺ faster.
• Cells balance NAD⁺ pools across the nucleus, cytosol, and mitochondria separately — boosting blood NAD⁺ doesn’t guarantee a big mitochondrial bump.
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Key takeaway for dosage:
• There’s a ceiling: above a certain point, enzymes and feedback loops turn extra NAD precursors into waste products or inhibitors.
• For most healthy adults in studies, 300–500 mg/day NR or NMN moves NAD⁺ significantly; beyond 1 g/day, gains flatten and side effects (like flushing or digestive upset) can increase.
Prompt:
What do we know about the biology of NAD taken as a supplement. By biology is meant does oral ingestion really result in improving what we know the molecule does. Also biology is replete with examples of just the right amount being critical and that suggests dosage matters
Response
NAD biology is tricky, because the molecule is central to metabolism but also because taking it as a supplement doesn’t work as cleanly as people often assume. Let’s break it down carefully.
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1. What NAD does in the body
• Core role: NAD⁺ (nicotinamide adenine dinucleotide) is a coenzyme that shuttles electrons in redox reactions — it’s essential for energy production (glycolysis, TCA cycle, oxidative phosphorylation).
• Other roles: It’s also a substrate for enzymes that regulate DNA repair (PARPs), gene expression (sirtuins), and cell signaling (CD38).
• Decline with age: Tissue NAD⁺ levels tend to drop with age and in certain diseases, which has spurred interest in supplements.
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2. The problem with taking NAD⁺ directly
• Poor absorption: NAD⁺ itself is too large and charged to cross cell membranes efficiently and is rapidly broken down in the gut.
• Blood stability: Even if some NAD⁺ gets absorbed, blood enzymes degrade it quickly into smaller molecules before it reaches cells intact.
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3. Why precursors are used instead
Most supplements aren’t pure NAD⁺ — they’re precursors that cells can convert into NAD⁺:
• Niacin (vitamin B3) — classic form, raises NAD⁺ but can cause flushing.
• Nicotinamide (NAM) — raises NAD⁺ but in high doses can inhibit sirtuins (feedback inhibition).
• Nicotinamide riboside (NR) — marketed for NAD⁺ boosting; shown to raise NAD⁺ in blood and some tissues in humans.
• Nicotinamide mononucleotide (NMN) — similar to NR, but one step closer to NAD⁺ in the biosynthetic pathway. Absorption route in humans is still debated.
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4. What the evidence says about oral supplementation
• Human trials: Small clinical studies show NR and NMN can raise blood NAD⁺ by ~20–60% within days to weeks.
• Tissue effects: Less clear — increases in muscle NAD⁺ are modest in healthy young adults, but more noticeable in older adults or those with metabolic issues.
• Functional benefits: Early human data suggest possible improvements in some measures (insulin sensitivity, vascular function), but effects are modest and not always reproducible.
• Animal vs human: Mice show bigger and more consistent benefits (lifespan extension, improved mitochondrial function) than humans so far.
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5. The dosage question — “just right” matters
Biology often follows a U-shaped curve:
• Too little NAD⁺ → impaired energy metabolism, DNA repair, resilience to stress.
• Too much NAD⁺ → potential issues:
• Sirtuin/PARP overactivation (could affect cell cycle or stress response).
• NAM accumulation from breakdown, which at high levels inhibits sirtuins.
• Possible support for growth of some cancer cells (since cancer often thrives on robust NAD⁺ metabolism).
• Most human trials use 250–1000 mg/day of NR or NMN and report it as safe for months to years — but long-term effects beyond that aren’t known.
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6. Key uncertainties
• Optimal target NAD⁺ level for different ages and conditions isn’t known.
• Which tissues benefit most from supplementation — blood NAD⁺ isn’t always a good proxy for brain, heart, or muscle.
• Whether long-term high-dose use has subtle downsides, especially in those without NAD⁺ deficiency.
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Bottom line
• Oral NAD⁺ itself doesn’t survive digestion well; precursors like NR and NMN do raise blood NAD⁺ in humans.
• There’s good biochemical evidence they work in principle, but the translation into large, lasting health gains in humans is still tentative.
• Dose likely matters a lot — both too little and too much could be counterproductive.
• At present, the strongest case for supplementation is in older adults or people with certain metabolic or mitochondrial disorders, not necessarily healthy young individuals.
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Prof Heather Cox Richardson’s post today, ChatGPT created bulletproof points
Key Issues Raised
Stock Market Decline & Economic Concerns
• Major stock market losses: S&P 500 (-2%), Dow Jones (-715 points, -1.7%), Nasdaq (-2.7%).
• Consumer confidence hit its lowest since January 2021 due to government policies.
• Rising inflation rates exceeded expectations, impacting market stability.
• Tariff policies raising concerns about prolonged inflation.
• Potential Federal Reserve reluctance to cut interest rates due to inflation.
Social Security System Overhaul
• Elon Musk’s “Department of Government Efficiency” (DOGE) attempting rapid migration of Social Security Administration (SSA) systems from COBOL to AI-driven systems.
• Concerns from experts about risks of errors, delays, and mismanagement affecting 65 million beneficiaries.
• Congressman Don Beyer experienced excessive wait times and system failures when calling SSA.
• Musk plans to step down from DOGE in May to avoid financial disclosures.
Shutdown of USAID
• State Department announced plans to dissolve USAID by July 1.
• USAID, created by Congress, cannot legally be shut down by the executive branch.
• The move aligns with Project 2025’s goal to consolidate executive power.
• USAID’s dissolution could weaken U.S. global influence and foreign aid efforts.
Public Health & Vaccine Controversies
• Dr. Peter Marks, top vaccine regulator, resigned, citing concerns over misinformation.
• Resignation tied to Health Secretary Robert F. Kennedy Jr.’s anti-vaccine stance.
• Marks warned about a growing measles outbreak (450+ cases).
• Kennedy appointed discredited anti-vaccine activist David Geier to study vaccines and autism.
• Widespread criticism from scientists and public health experts.
Defense Department Controversies
• Defense Secretary Pete Hegseth hired his younger brother Phil Hegseth, raising nepotism concerns.
• Military attack plans against Houthis in Yemen leaked on the unsecure Signal app.
• National Security Advisor Mike Waltz revealed Israeli intelligence, straining U.S.-Israel relations.
• Military personnel angry over perceived double standards for leadership versus rank-and-file soldiers.
• Republican Rep. Victoria Spartz faced backlash for refusing to call for resignations.
Upcoming Special Elections & Political Backlash
• White House appears worried about April 1 special elections.
• Florida’s District 6 race unexpectedly competitive; Trump campaigned for GOP candidate Randy Fine.
• Democrat Josh Weil outraised Fine nearly 10-to-1, polling within the margin of error.
• Florida District 1: Democrat Gay Valimont outraising Republican Jimmy Patronis in a deep-red district.
• Republicans scrambling to hold seats, with Elon Musk donating heavily to GOP candidates.
Wisconsin Supreme Court Election & Election Integrity Issues
• Musk donated $20M to Trump-backed candidate Brad Schimel in the Wisconsin Supreme Court race.
• Court balance could determine voting laws and district maps for decades.
• Musk’s campaign tactics included offering $1M prizes to voters, violating Wisconsin election laws.
• Wisconsin Attorney General sued to block Musk’s payments to voters.
• Widespread criticism of Musk’s attempts to influence elections with money.
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Reversing progress in alternate energy sources to limit climate change
Excerpt
beg the question of why it is necessary to boost production at all if demand is indeed so much weaker than before. The answer was recently provided by none other than the head of the International Energy Agency, Fatih Birol.
At CERAWeek, Birol said that the world needs upstream investments in existing oil and gas fields to support global energy security. Many saw these remarks as a stark departure from his usual refrain over the past few years, which has focused on the perceived success of the energy transition that would eliminate the need for hydrocarbons pretty soon. Indeed, that’s exactly what they were.
https://oilprice.com/Energy/Crude-Oil/New-Oil-Projects-Set-to-Flood-Market-in-2025.html
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A second PhD in psychology for Professor Heather Cox Richardson, Boston College
As a PhD in Chemistry I would second the analysis she published yesterday as it is a critical and missing piece of the puzzle to explain the outlandish actions by MAGA that the world is being drowned in
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MAGA hack that explains their confidence
2022 the work began 
Weeks before the election 
Election machines and Leonard Leo 
Strategy was in place 
Greg Palast warned 
The funding was in place -
Putin played Trump
The 2025 Putin–Trump call was a formal telephone conversation between U.S. President Donald Trump and Russian President Vladimir Putin that President Trump said took place on February 12, 2025.
Aggregation of reports of this call, that I consider an ongoing pattern of a fascist alliance between Putin and Trump who share the ideology.
1. Why did Putin agree to an “immediate ceasefire on all energy facilities”? Anyone who has ever tried negotiating with russia understands this tactic.
Putin will continue targeting Ukraine’s critical infrastructure while claiming that russia is only striking “military facilities.” Meanwhile, he will accuse Ukraine of violating the ceasefire agreement.
By
Roman Sheremeta
Professor of Economics, Board Member at Save Ukraine and Ukrainian American House
Weatherhead School of Management at Case Western Reserve
University • Purdue University
Cleveland, Ohio, United States
Source: LinkedIn 20 March 2025
2. Another article from LinkedIn with supporting data
3. President Zelenskyy speaks about the Putin Trump call
4. The betrayal by Putin from a different writer
5. Trump’s former national security advisor perhaps has insider intelligence and knowledge. Here is what he has to say
6. BBC reporting of the talks
7. The call was purposeless, war resumes
BBC reports resumption of the war
8. Professionals with a view of ethics that is based on an understanding of “common good” and “virtue”.
9. An explanation of the call
10. Behind the scenes, during the call
11. The counter argument by Breitbart
12. The betrayal from the perspective of a journalist, attorney and filmmaker in Substack
LinkedIn post of a Substack post
13. The refusal by to accept the non starter
14. Why negotiations fail
15. Russian attack violates agreement
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Truth and Politics
What does truth mean.
One way to look at it is this: essential nature of the thing. As long as a process conforms to the nature of things, it will be sustainable.
Political systems are constructs that are useful. In order for the system to be sustainable, it should conform to the nature of “human beings”.
The ideals of liberty, freedom, justice conforms to human nature only when your view of”human” is science evidence based. Namely Homo sapiens. You have to learn to respect humans because you know first hand about qualia or the private nature of your mind and can understand to respect it. Another way of saying do unto others what you would have them do unto you or the law of karma in behavior.
Therefore what is sustainable is the American constitution which is being demolished by MAGA. If adopted by all countries it will be like a pendulum swinging between conservative and liberal ends of fiscal policy and social policy.
Dialogue in society is critical for which the first Amendment and a separation of church and state are the critical elements from the American experiment in liberty, freedom and justice which is under an existential threat from the current administration
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Brahmins under attack by the world’s most powerful Vaishya a lower caste
This Professor of American history writes professional journal publications quality analysis using simple English and all her posts are explaining events unfolding in the coup underway in Washington DC.
In this piece I chose to highlight segments as screenshots and provide a link in the comments to the entire piece.
The greatest impact of all these actions by the Trump administration will be on the most vulnerable sections of society and in fact on their supporter base.
Professionals who have education should remember that knowledge acquired is never paid for through money. Knowledge acquisition and sustenance is provided by society supporting the upper caste Brahmins in all societies. The Brahmin is the mindset that values knowledge over wealth and they are the selfless servant leaders of knowledge workers who become scientists dedicating their lives to acquiring and furthering knowledge. The US government was the world’s largest patron of the world’s largest agencies of Brahmins furthering scientific knowledge in all frontier areas. A real Brahmin would choose to work there than for a profit seeking Vaishya (lower caste) entity.
We are seeing a historical demolition of the structure of world’s greatest institution of research, the Crown Jewels of America being plundered by Elon Musk, who floated a lottery to elect a real estate agent who admitted he gained power through as yet undiscovered sleight of technological meddling.
Who is Heather Cox Richardson 
Snippet of a piece whose link will be added 
Second snippet https://www.facebook.com/share/p/18s2ToGx2L/?mibextid=wwXIfr
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Coup on the Titanic by a real estate developer
Current historical fiction, or a view from my on the job experience
So here is the deal with automation. You hire a few jocks who have demonstrated an ability to parse code and alter it to meet the new requirements you provide.
They don’t follow any software engineering best practices because that is too expensive.
Why is that too expensive – because every small change, however innocuous looking from a logic perspective has a potential unforeseen impact.
Major corporations have processes in place where the business process owners, generally the finance folks who have an eye on revenue impact have a lot more say as do supply chain business that looks at potential impact to shipping to customers.
So, IT folks like me who can span across the silos speaking the language of each silo, while also not just talking to coders but also documenting the design changes and getting each change “certified” to move to production before it goes to production and are also on “the hook” if anything goes wrong soon after or later.
Why do we need this expensive process, a real estate developer might ask. The way you run a yacht with a staff of 4 is not the way you run the titanic.
Right now you have a real estate developer eyeing Gaza run the titanic of all titanics conducting a coup while it’s occupants are busy arguing – give him a chance
This narrative is drawn from studying software engineering in graduate school for computer science, business process management using ERP Accenture and later applying it on the job at 4 companies, McAfee, PepsiCo, Verizon and currently Johnson & Johnson.
By the way if you come across my rants supporting Science, about the same real estate developer at the helm of the coup on the Titanic, that comes from a decade and a half working as faculty teaching and conducting research in India and the US.
Inspired by Bertrand Russell’s Conquest of Happiness, I found happiness in servant leadership and I have no concept of retirement because happiness is found in service. In America, I’ve seen a lot of older folks doing volunteering which makes this nation great.
What is my rant about this post I am sharing- these are corporate raiders raiding the largest corporation that has a constitution to strip it of its expensive processes which no successful business would allow unless they are in bankruptcy court
Remember, USA is not in bankruptcy like MAGA makes it appear because they are corporate raiders who want the chattel to do their bidding and not question them
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Support Ukraine save democracy
Senator Tillis explains why
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We were forewarned
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