Nano-Hydroxyapatite (nHA): Safety, Controversy & Oral Health

Nano-hydroxyapatite (nHA) is a form of hydroxyapatite, the naturally occurring mineral that makes up the majority of our tooth enamel, broken down into ultra-fine particles. Because of its smaller particle size, nHA can penetrate more deeply into the enamel surface, making it especially effective for addressing tooth sensitivity and repairing early enamel erosion. However, despite its promising benefits in oral care, nHA has been the subject of some controversy, particularly concerning its safety and whether it can cross the blood-brain barrier.

First and foremost…is hydroxyapatite really the perfect fluoride replacement it’s sometimes marketed as?

I’ll be the first to admit that I’ve probably oversimplified this conversation before, but I’ve learned oral health simply isn’t that black and white. And I think making blanket claims that everyone can automatically swap fluoride for hydroxyapatite (or another mineral toothpaste) without considering individual risk factors is misleading.

With that being said, I LOVE nHA. I genuinely think it’s one of the most exciting things to happen in oral care. And I absolutely believe is can be a fantastic option for many people, particularly lower-risk individuals with healthy saliva flow, strong oral hygiene, balanced diets, and minimal cavity history. But I also think it’s being misrepresented online.

The reality is that hydroxyapatite simply does not yet have the same depth of long-term clinical evidence behind it that fluoride does for high-risk cavity prevention, especially in children. That doesn’t mean hydroxyapatite is ineffective. It doesn’t mean future evidence won’t continue growing. And it definitely doesn’t mean fluoride is the only answer.

Is nHA toxic?

Concerns about the safety of nano-hydroxyapatite (nHA) toothpaste often stem from early toxicological studies in animals, many of which involved intraperitoneal injections (an exposure route that does not reflect how humans use toothpaste).

A 2016 report by the European Commission’s Scientific Committee on Consumer Safety noted that extremely high doses of nHA caused serious effects such as cardiac and respiratory arrest in rats, along with tissue-specific impacts like lung proliferation, liver oxidative damage, kidney disruption, blood cell interference, and DNA damage. However, these outcomes occurred under unrealistic experimental conditions involving high systemic doses, not topical application.

For example, in this study, nano-hydroxyapatite (nHA) was administered to rats via oral gavage - a method involving delivering the nHA directly into the stomach using a tube. In this study, the nHA was delivered via intravenous injection, and this study was delivered through an injectable paste.

The Blood-Brain Barrier Debate

One common concern raised is whether nano-hydroxyapatite from toothpaste can cross the blood-brain barrier. This fear is largely based on misinterpretations of research. Some studies in medical literature do involve engineered nanoparticles designed to target the brain for drug delivery, particularly in the treatment of central nervous system diseases. However, those particles are specifically engineered to cross the blood-brain barrier and are delivered through routes like injection or nasal sprays - not brushed onto teeth.

Read more about nHA crossing the BBB here.

Can nHA Reach the Brain from Toothpaste?

For a substance in an oral care product to penetrate the blood brain barrier we have to ask: how is it going to get there? To enter the brain from a toothpaste, a substance would first need to enter systemic circulation, either through the gut or oral mucosa.

Gut absorption is unlikely because nano-hydroxyapatite dissolves in the highly acidic environment of the stomach, which has a pH of 1.5–3.5. nHA begins dissolving at a pH of 4, meaning it would likely break down before ever reaching the bloodstream. And as mentioned earlier, studies show it does not penetrate the oral epithelium either.

The stomach has a pH of 1.5–3.5. nHA begins dissolving at a pH of 4.

Will future research show that it actually can via properly used toothpaste route? Sure, maybe. But right now we can only go off of what we know. Like...

Research on Topical Use in Oral Care

When it comes to oral care specifically, available research paints a very different picture. A key study evaluating toothpaste containing 10% nano-hydroxyapatite applied the substance directly to oral mucosa and found no penetration through the oral epithelium. This means the nHA remained on the surface and did not enter the bloodstream or systemic circulation. Furthermore, applying 10% nHA (50 nm particle size) to both keratinized and non-keratinized oral tissues for 24 hours found no evidence of tissue penetration, supporting the conclusion that systemic absorption through the mouth is highly unlikely.

When looking at research it's important to understand the full context behind the findings before trying to compare to oral care products: Is the particle shape known? Do they give the concentration? What was the method of delivery? How was the nHA prepared/for what purpose? What is specifically engineered to cross the BBB?

Was nHA banned in the EU?

This is a common, simplified misconception. The EU didn’t completely ban nano-hydroxyapatite (nHA). Instead, the SCCS raised questions about the safety of certain nano-sized particle forms and characteristics, then later determined that specific formulations could be considered safe within set concentration limits after additional safety data was provided.

Basically, particle shape and concentration matters.

Particle Shape Matters

There are four main shapes of hydroxyapatite crystals: rod, sphere, amorphous, and needle. Research to date has only evaluated the rod-shaped and amorphous particles for safety in oral care products. The needle-shaped particles have not yet been studied in this context.

Concentration Matters

In 2023, the European Union released an official opinion confirming that nano-hydroxyapatite is safe for use in toothpaste at concentrations up to 10%, provided the particles are rod-shaped and not surface-coated or chemically modified. This highlights the importance of checking product labels (or reaching out to companies) for both concentration and particle shape to ensure you're using a well-tested form of nHA.

Pretty much all the commercial nHA toothpaste on the market is going to be 10% or below. While there isn’t usually a strict “ban” against higher concentrations, exceeding 10% could trigger regulatory scrutiny or require additional safety testing and approvals before a product can be marketed.

https://health.ec.europa.eu/publications/hydroxyapatite-nano-0_en

Additionally, there is some debate as to what the most effective concentration is. Research indicates that toothpaste formulations containing nHA at concentrations lower than 10% may be less effective in remineralizing enamel and reducing tooth sensitivity (1,2, 3, 4). However, there is also research indicating that lower concentrations may be just as effective as well (1, 2), especially if the source of the nHA is NanoXIM (as low as 3%) (1, 2, 3).

My Thoughts

I've gone back and forth on my personal thoughts on this. I have had conversations with Dr. Jennifer Eisenhuth who created Dr. Jen's 10% nHA toothpaste (one of the very few 10%), and she is pretty adamant that anything under 10% is unlikely to provide true remineralization. But then there's Dr. Mark Burhenne, who disagrees. He created Fygg which is 3.1%, and I highly admire and respect him. When all the talk about "10% only" came out, he actually second guessed his own product and conducted his own research.

I personally remineralized a spot by using Risewell's Pro toothpaste with contains 5% nHA (and 10% micro), BUT I also did ozone therapy so I can't say with 100% confidence that the toothpaste alone helped or not.

But my initial leaning is for overall oral care and maintenance you'll probably be just fine with 3-5% if you have a strong and healthy oral environment to start off with.

If you are prone to cavities, then there is a deeper root cause that is worth evaluation. Toothpaste can be a supportive tool, but it is not a cure. I would highly recommend a consult with a biologic, airway focused dentist.

Naturally Derived nHA from Eggshells

Most nHA toothpaste is made synthetically, which isn't necessarily a bad or "toxic" thing. But if this is something you'd still like to stay away from, there is naturally derived nano-hydroxyapatite, such as that sourced from eggshells, has shown promising safety data. A 2024 study published in the Arab Gulf Journal of Scientific Research concluded that eggshell nHA exhibited no toxicity toward human osteoblast and fibroblast cells, and even enhanced cell viability, making it a biocompatible option for dental use. Dr. Jen has a great egg-shell nHA derived toothpaste.

What about Micro-Hydroxyapatite (or non-nano)?

This research article reflects a scientific consensus, backed by 37 studies, indicating that micro-HA crystals are largely ineffective. While they may offer limited surface-level remineralization, their significantly larger size compared to natural enamel HA and dentinal tubules reduces their overall effectiveness in promoting deeper remineralization and alleviating sensitivity.

Conclusion: Is nHA Safe in Toothpaste?

In summary, while high-dose animal studies raised theoretical concerns about nano-hydroxyapatite, these scenarios do not reflect real-world exposure via toothpaste. Current research supports the safety of nHA in oral care when used at or below a 10% concentration, particularly when composed of rod-shaped particles. Misinformation often arises from unrelated research on drug delivery nanoparticles and does not apply to topical dental products. Based on the evidence available, nano-hydroxyapatite remains a promising and safe ingredient for remineralization and sensitivity relief when used appropriately.

Damned if You Do, Damned if You Don't

This can certainly feel like the case when it comes to topics where one "expert" says xyz is great, and another says it's terrible. But at the end of the day it's not a black and white subject matter. Everyone has different risk factors, and those factors are going to determine the "best" option.

Cavities are More than Toothpaste

At the end of the day, our biggest focus should be protecting teeth from the inside out and looking at the overall state of the oral microbiome when someone is struggling with cavities. Cavities are multifactorial and not simply about toothpaste. Saliva quality matters. Mouth breathing matters. Airway health matters. Diet matters. Feeding habits matter. Sleep matters. Bacterial load matters. Overall systemic health matters. Toothpaste can only do so much.

That’s why I think focusing exclusively on finding the “perfect” toothpaste ingredient can sometimes miss the bigger picture entirely. More important than obsessing over fluoride versus hydroxyapatite vs whatever else is being talking about online is asking why someone is cavity-prone in the first place.

What does their nutrition look like? Are they constantly snacking? Are they mouth breathing or snoring? Do they have poor saliva flow, airway issues, or high pathogenic bacterial loads? And most importantly…why?

Those are the questions that matter long term. Root cause matters.

Toothpaste Hasn't Always Been Necessary

The reality is, toothpaste hasn’t always been necessary for humans to maintain healthy teeth. Dental disease is deeply connected to overall systemic health. When the body is properly nourished, breathing well, developing correctly, and supported with the nutrients needed for remineralization, saliva itself can help protect teeth by maintaining a healthier oral environment and supplying minerals to the enamel.

Unfortunately, most of us don’t live in that ideal environment today. Modern diets, chronic inflammation, processed foods, stress, poor sleep, airway dysfunction, and altered oral microbiomes have dramatically changed the landscape of oral health, especially in Western societies. Our mouths are often in a much more acidic, dysbiotic state that favors the growth of cavity-causing bacteria.

And we can see this reflected historically. Early 20th century records (1,2) documented extremely low rates of tooth decay in pre-contact Inuit populations despite the absence of toothpaste. By the 2000s, surveys showed cavity rates in Inuit preschoolers had risen dramatically following major dietary and lifestyle shifts. Weston A. Price also famously observed far lower cavity rates in isolated indigenous populations eating traditional diets compared to groups consuming more processed Western foods.

Weston A. Price compared isolated indigenous diets vs Western processed diets, and found only 0.1% of traditional indigenous diet teeth had cavities, vs 23% in processed-diet groups. 

Audette AJ, Anello F & Johnson RR (2021) Comparison of traditional indigenous diet and modern industrial diets and their link to ascorbate requirement and status. J Orthomol Med. 36(1)

Toothpaste is a Tool

BUT…all this doesn’t mean toothpaste is useless either, especially in today’s world. Toothpaste is still a tool, and the right tool may provide an important extra layer of protection while you work on addressing those deeper root causes - and that "right tool" may look different for everyone.

Final Thoughts

At the end of the day, hydroxyapatite simply does not yet have the same level of long-term clinical evidence that fluoride does for high-risk cavity prevention. That doesn’t mean it’s ineffective or toxic, and it doesn’t mean the research won’t continue to grow. Personally, I think the evidence we do have is very promising and moving in a positive direction. Will I be proven wrong in the future? Maybe. But like anything still being actively studied, we can only base decisions on the evidence currently available.

If you’re low-risk and seeing great results with hydroxyapatite, that’s wonderful - keep going. But if you’re higher-risk, it may be worth looking at and discussing all available options rather than assuming there’s a one-size-fits-all answer. I’ve personally seen remineralization happen with hydroxyapatite, but there have also been times where we’ve chosen fluoride too.