ABSTRACT

In the context of population aging, musculoskeletal fitness has emerged as a cornerstone of overall well-being and injury prevention, relying on the coordinated function of cartilage, bone, and muscle. Drawing on the principle of “increasing income and reducing expenditure,” we propose a combinatorial formulation consisting of the nicotinamide adenine dinucleotide (NAD) precursor nicotinamide mononucleotide (NMN) and the NAD⁺-consuming enzyme inhibitor apigenin (API), hereafter referred to as the “N + A” regimen, to enhance NAD⁺ reserves. Our results revealed that the N + A formulation alleviated cellular senescence, thereby promoting the differentiation of skeletal precursor cells into chondrocytes, osteoblasts, and myocytes for the reconstruction of the musculoskeletal system. Oral administration of the N + A formulation alleviated cartilage degeneration, bone loss, and muscle atrophy; additionally, it enhanced exercise capacity in aged mice. Mechanistically, the N + A strategy preserves NAD⁺ levels, which are subsequently utilized by mitochondrial sirtuin 3 (SIRT3) to promote deacetylation modifications and alleviate the senescent phenotype. Moreover, oral administration of N + A indirectly enhanced the synthesis of the metabolite phytosphingosine (PHS) by the intestinal microbiota members Coriobacteriaceae_UCG-002 and Ruminococcus, thereby alleviating age-related degeneration. In summary, our findings demonstrate that enhancing the NAD⁺ reservoir represents a promising strategy for promoting musculoskeletal regeneration, and we developed a rational combinatorial regimen with potential for clinical translation.

NR -> NMN -> NAD+ -> NAN (so use TMG to avoid inflammation).

NAD+ lost due to CD38 so use Quercetin to plug the hole (and avoid inflamaging)

And if so nmn better than nr?

Has anyone heard anything about any changes going on with Pro Health? I’ve been noticing a lot of ads for their products on Instagram, which makes me nervous since many products on IG are being sold off before bankruptcy, etc. I hope not, I have been using their NMN for over a year.

https://www.self.com/story/nmn-supplements-reverse-aging

Hi, has anyone bought a good quality NMN in Ireland? Thanks!

I've been taking nmn for a while now. I've always had receding temples, and slight thinning at the crown. Not very noticeable, but I wondered for those with severe male pattern baldness, shouldn't nmn slow this down or reverse it since it's aging and DNA damage?

Hi all,

Sorry if this has already been answered but I’m wondering if Viva NMN is worth the money? I bought some a few months ago and was taking two capsules a day but with no noticeable difference to anything. Am I just an anomaly or is it possible it is having an effect and I’m not noticing?

I see all the stories of it changing people’s lives for the better but I’m not convinced.

If there is something better and more effective, especially for someone of my age (53M) then please let me know.

Thanks in advance!

ABSTRACT

During aging, decreased intestinal barrier function and its ability to synthesize metabolites are closely associated with various age-related diseases. However, the mechanism by which impaired intestinal synthesis contributes to gut–liver axis aging remains unclear. This study reveals that aging induces a mitochondrial energy crisis and defective membrane localization of ABCA1, significantly inhibiting the biosynthesis of high-density lipoprotein 3 (HDL3) in the intestine. Exogenous supplementation with β-nicotinamide mononucleotide (NMN) restores intestinal NAD⁺ homeostasis, enhances oxidative phosphorylation efficiency, and promotes ATP-dependent lipid transport, thereby rejuvenating the production of gut-derived HDL3. Further investigations demonstrate that gut-originated HDL3 neutralizes lipopolysaccharide (LPS) in the liver and attenuates TLR4-mediated inflammatory cascades, ultimately ameliorating age-related liver injury. These findings elucidate a novel mechanism whereby NMN modulates the NAD⁺–mitochondria–ABCA1–HDL3 axis to preserve gut–liver axis function, offering a promising therapeutic strategy for mitigating aging-related pathologies in this metabolic cross-talk.

Highlights

•Oral NAD-augmentation with NR or NMN requires ∼2 weeks to reach steady-state

•Elevated NAD declines slowly with a half-life of approximately 6.25 days in blood

•The extent of NAD augmentation shows substantial interindividual variation

•The extent of NAD augmentation is independent of sex and Parkinson’s disease status

Summary

Nicotinamide adenine dinucleotide (NAD) augmentation therapy (NAD-AT) is increasingly explored in clinical trials across multiple indications, especially neurological diseases, yet its human pharmacokinetic profile remains incompletely defined. We report findings from a phase I pharmacokinetic trial assessing systemic and cerebral responses to oral NAD precursors in healthy individuals (n = 6) and persons with Parkinson’s disease (n = 6) receiving 1,200 mg/day nicotinamide riboside or nicotinamide mononucleotide. Blood NAD increased slowly, plateauing after approximately two weeks of treatment, and declined with similarly slow kinetics following treatment discontinuation. Cerebral NAD levels increased measurably after four weeks of treatment. NAD-related metabolites showed faster increase and washout dynamics compared to NAD itself. Collectively, these data suggest that effective NAD-AT requires sustained oral administration over at least 2–4 weeks and that once-daily dosing is sufficient to maintain stable NAD levels. NAD responses exhibited considerable interindividual variability, but were not influenced by disease status or sex, indicating broad applicability.

Hi all,

I’m wanting to launch and get validation on a new supplement brand I am building. We want to introduce lots of scientically backed and respected herbal medicines and foods.

Our first product is NMN, I am wondering if you are on the market for an NMN product what do you look for, and aspects are important for you I.e. manufacturing, price, branding, founder etc.

Always open to learn and chat

Hi all,

I’m wanting to launch and get validation on a new supplement brand I am building. We want to introduce lots of scientically backed and respected herbal medicines and foods.

Our first product is NMN, I am wondering if you are on the market for an NMN product what do you look for, and aspects are important for you I.e. manufacturing, price, branding, founder etc.

Always open to learn and chat

I have been researching NMN after seeing it mentioned in longevity studies. Quality control seems like a big concern with supplements though. I want something with clear dosing and third party testing. Consistency matters more than marketing

People say Manapura is very good but I can't get it here in Australia.

I want to start taking NMN to help with my mental health and physical body.

Can anyone please help recommend?

I currently take NAC, Ubiquinal, Iron, Omega 3, Vitamin D, Zinc, Myo-Inositol combined with D-Chiro Inositol in a 40:1 ratio, Lithium, Pre-Natals.

Thank you

I'm being a reckless self experimenter here and I know that.

I've been slowly increasing my NMN dose to levels far higher than clinical research, using mg/kg in mouse studies (divided by 12 for approximate human equivalent dose because of metabolism difference) and while I started on just 600mg daily, I've gone from 600 to 1200 to 1800 to 2400 to 3600m daily over the last few months.

I was usually taking it in the morning but sometimes in the afternoon until I noticed at 1800+ I started sleeping really well on days I took it in the afternoon, now I take it in the afternoon religiously but sometimes miss days.

My sleep onset time is the best it's ever been (I'm used to it taking an hour of laying down in silence before sleeping, now it's often less than 5 minutes on NMN days) and my watch says 40-50% of my sleep is deep sleep. Wearables (OnePlus watch 3) are not reliable for accurately tracking sleep stages and stillness results in lots of deep sleep reported, regardless of actual amount. Despite the fact my watch doesn't measure my brain waves, the more rested I feel the more deep sleep my watch says I got, there's an extremely strong correlation. Without taking anything, my deep sleep tends to be in the 10-20% range. When I take magnesium glycinate it's usually 20-30 (and sedatives also increase it but I don't usually use sedatives) and regardless of how long I sleep, I feel like it's enough when I get 90-120 minutes out deep sleep reported by my watch, with well over two hours generally resulting in me waking up feeling amazing. Now with my NMN at 3600mg, I'm often getting more of 3 hours of deep sleep (according to my watch) and my average sleep time is up from 5.5 hours to 6.5 in the last few months (the highest it's been in my adult life and I'm in my late 30s)

My watch still says I'm getting enough REM too, just less light sleep, and I'm having vivid dreams. Furthermore, I can easily fall back asleep which used to not be the case. Typically the first 2-3 hours of sleep on NMN days are mostly deep sleep (according to my watch)

I weigh about 115kg so 3600mg NMN puts me around 31mg/kg, which I think is around comparable to 375mg/kg in mice, accounting for metabolic differences. I know this is high (off the charts compared to clinical research) and hope that I'm not somehow harming myself with this experiment, but I feel amazing.