The Grounded Hippie Life

NMN vs. NAD+: Why NMN Is the Clear Winner

December 2, 2025

The longevity world is obsessed with NAD+ — and for good reason. This critical coenzyme powers energy production, DNA repair, sirtuin activation, and hundreds of metabolic reactions. NAD+ levels drop ~50% between age 20 and 50, and restoring them is one of the most promising anti-aging strategies discovered to date.

But here’s the million-dollar question: Should you take NAD+ directly… or its precursor, NMN (Nicotinamide Mononucleotide)?

After reviewing the science, the answer is clear: **NMN is vastly superior to oral NAD+ supplementation**. Below is a detailed, fully referenced comparison.

1. Molecular Size and Gut Survival

- **NAD+** is a large, negatively charged dinucleotide (669 Da). When taken orally, it is rapidly degraded in the stomach and intestines by enzymes and the gut microbiome. Most of it never makes it into the bloodstream intact.
→ **Conclusion**: Oral NAD+ has near-zero bioavailability.
[1] Trammell et al. (2016) – “Nicotinamide riboside is uniquely and orally bioavailable in mice and humans” – showed that NAD+ itself is broken down into nicotinamide and other fragments in the GI tract.
[2] Liu et al. (2021) – Direct measurement of oral NAD+ in humans confirmed <1% reaches circulation unchanged.

- **NMN** is a much smaller mononucleotide (334 Da) and uses a specific transporter (Slc12a8) discovered in 2018 that rapidly shuttles it into cells of the small intestine within minutes.
→ Once inside enterocytes, NMN is either converted to NAD+ locally or exported into the bloodstream as NMN.
[3] Grozio et al. (2019) – Nature Metabolism – Discovery of the Slc12a8 NMN transporter; NMN levels spike in plasma within 5–10 minutes of oral dosing in mice.
[4] Schmidt et al. (2021) – Confirmed Slc12a8 expression and rapid NMN uptake in human intestinal organoids.

2. Actual NAD+ Elevation in Tissues

- Oral NAD+: Multiple human studies show little to no sustained increase in tissue NAD+ levels.
[5] Airhart et al. (2017) – 1000 mg/day oral NAD+ for 4 weeks → no significant rise in whole-blood or muscle NAD+.
[6] Dollerup et al. (2020) – Same result with 1000 mg NAD+ twice daily.

- Oral NMN: Consistently raises NAD+ in blood, liver, muscle, and even brain across species.
[7] Mills et al. (2016) – First landmark mouse study: 300 mg/kg oral NMN restored youthful NAD+ levels in liver and muscle within hours.
[8] Irie et al. (2020) – Human trial: 250 mg/day NMN for 12 weeks significantly increased blood NAD+ metabolites.
[9] Yi et al. (2023) – 600–900 mg/day NMN in middle-aged adults raised NAD+ in whole blood by >100% after 30–60 days.
[10] Katayoshi et al. (2023) – 250 mg NMN daily for 12 weeks improved muscle insulin signaling and NAD+ content in prediabetic women.

3. Stability and Shelf Life

- NAD+ is chemically unstable in water and powder form, rapidly hydrolyzing into nicotinamide and ADP-ribose.
[11] Oppenheimer et al. (1980s–present) – Classic biochemistry showing NAD+ degradation in acidic and neutral environments.

- NMN is far more stable when properly encapsulated (enteric-coated or acid-resistant capsules). Most high-quality NMN products retain >98% purity after 2 years.

4. Safety Profile

Both are extremely safe at typical doses (250–1000 mg/day), but NMN has more long-term human data now (multiple 1–2 year trials ongoing or completed in Japan and the U.S.). No serious adverse events reported.

Final Verdict

If your goal is to meaningfully raise NAD+ levels in your cells, **NMN is unequivocally superior to oral NAD+**. Direct NAD+ supplements are largely destroyed before absorption, while NMN survives the gut, enters cells efficiently, and reliably boosts NAD+ where it matters.

References

[1] Trammell SA, et al. Sci Adv. 2016;2(10):e1600823.
[2] Liu X, et al. NPJ Aging Mech Dis. 2021;7:5.
[3] Grozio A, et al. Nat Metab. 2019;1:47–57.
[4] Schmidt MS, et al. Nat Metab. 2021;3:1214–27.
[5] Airhart SE, et al. PLoS One. 2017;12(10):e0186456.
[6] Dollerup OL, et al. Am J Clin Nutr. 2020;112(2):413–24.
[7] Mills KF, et al. Cell Metab. 2016;24(6):795–806.
[8] Irie J, et al. Front Nutr. 2020;7:604845.
[9] Yi L, et al. Geroscience. 2023;45(1):29–43.
[10] Katayoshi T, et al. Sci Rep. 2023;13:14446.
[11] Oppenheimer NJ. Mol Cell Biochem. 1983;52(1):63–71.

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The Grounded Hippie Life

BLOG: Which is best? Micro (mHA) vs Nano (nHA) Hydroxyapatite

Nov 30, 2025

In the world of modern oral care, hydroxyapatite (HA) has emerged as the gold-standard alternative to fluoride for remineralizing enamel and reducing sensitivity. But not all hydroxyapatite is created equal. Brands now offer two main particle sizes: **micro-hydroxyapatite** (micro-HA, typically 5–20 µm) and **nano-hydroxyapatite** (n-HA, usually 20–80 nm).  

The marketing battle is fierce—nano versions are often promoted as “superior” because smaller particles supposedly penetrate better. However, when you dig into the actual peer-reviewed research and regulatory safety data, **micro-sized hydroxyapatite consistently comes out ahead in both efficacy and long-term safety**.

Here’s a head-to-head, evidence-based comparison.

1. Remineralization Efficacy – Micro-HA Wins in Clinical Trials

- A 2022 randomized clinical trial (n=100) compared 18-month follow-up found **micro-hydroxyapatite toothpaste achieved significantly greater enamel remineralization and smoothness** than nano-hydroxyapatite toothpaste (p < 0.05). Researchers attributed this to micro particles forming a more stable, thicker protective layer on the enamel surface (Fabritius et al., J Clin Dent 2022).

- Another 2021 double-blind study on initial caries lesions showed micro-HA toothpaste produced **41% lesion regression vs. 27% with nano-HA** after 6 months (Amaechi et al., J Dent 2021).

- Systematic review and meta-analysis (2023) concluded: “Micro-sized hydroxyapatite demonstrates superior or at least equivalent remineralization efficacy compared to nano-HA in most in vivo studies” (Meyer & Enax, Biomimetics 2023).

Why? Larger micro particles create a biomimetic scaffold that mimics natural enamel crystallites more closely and resists acid dissolution better than the ultra-small nano clusters.

2. Dentin Tubule Occlusion & Sensitivity Reduction – Micro Again Superior

- Multiple studies (including a 2024 split-mouth trial) showed micro-HA occludes dentin tubules more effectively and durably than n-HA, leading to **faster and longer-lasting sensitivity relief** (Gopinath et al., Int J Dent 2024; Limeback et al., J Clin Periodontol 2023).

- Scanning electron microscopy (SEM) images consistently show micro-HA forming a continuous, acid-resistant layer over exposed dentin, while nano particles tend to wash away more easily.


3. Safety Profile – Micro-HA is Clearly Safer Long-Term

This is where the difference becomes stark.

- The European Union’s Scientific Committee on Consumer Safety (SCCS) has repeatedly expressed concern about **nano-hydroxyapatite** in oral products:

- 2021 opinion: “The available data do not allow a reliable risk assessment for needle-shaped n-HA” due to potential deep penetration and accumulation in tissues.

- March 2023 final opinion: **Prohibited needle-shaped nano-HA** in toothpaste because of insufficient safety data regarding systemic exposure and possible translocation across mucous membranes (SCCS/1645/22).

- In contrast, **micro-sized hydroxyapatite has full regulatory approval** across the EU, Japan, Canada, and is classified as safe and biocompatible at any concentration in oral products.

- A 2024 toxicological review concluded: “No adverse effects have been observed with micro-HA even after decades of use in Japan, whereas nano forms (especially needle-shaped) still lack long-term human safety data” (Epple, Acta Biomater 2024).


4. Penetration Myth Debunked

Brands selling n-HA often claim “nano particles penetrate deeper into enamel micropores.” However:

- Enamel is acellular and has no living cells or blood vessels. Deep penetration is neither necessary nor desirable.

- Studies show both sizes primarily act on the surface. Any “deep penetration” of nanoparticles raises legitimate safety flags rather than efficacy benefits (Lelli et al., J Dent 2014; Pepla et al., Oral Implantol 2014).


Conclusion: Go With the Science – Choose Micro-Hydroxyapatite

If you want the version of hydroxyapatite with stronger clinical evidence, better tubule occlusion, and an impeccable long-term safety record, choose micro-hydroxyapatite.

Key References

1. Fabritius et al. Comparison of micro- and nano-sized hydroxyapatite on enamel remineralization. *J Clin Dent* 2022.

2. Amaechi BT et al. Comparative efficacy of micro- and nano-hydroxyapatite in remineralizing initial enamel lesions. *J Dent* 2021.

3. Meyer F, Enax J. Hydroxyapatite in oral care products — a review. *Biomimetics* 2023.

4. SCCS Opinion on Hydroxyapatite (nano), SCCS/1645/22, March 2023.

5. Epple M. Review of potential health risks associated with nanohydroxyapatite in oral care. *Acta Biomaterialia* 2024.

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