Oral diseases, such as tooth decay and erosion, are the most prevalent diseases of humankind, affecting nearly 3.5 billion people worldwide.
Early in the 20th century, the connection between fluoride and healthy teeth was discovered and since the mid-20th century, water fluoridation and fluoride containing oral care products have provided the mainstay of oral health treatment in many countries. However, over the course of the 20th century, evidence began to accumulate showing the consumption of dairy products, too, might lead to improved oral health.
For our March Speaking of Science, we were joined by Laureate Professor Eric Reynolds AO of the University of Melbourne to discuss his discovery of new dairy based technologies that have since gone on to significantly improve dental health both in Australia and globally.
Watch and listen as Professor Reynolds discusses the decades of NHMRC supported research that has impacted dental health care and improved the smiles of many.
Recorded on Monday 23 March 2026 at 11:00AM-12:00PM.
- Video transcript
00:03 Professor Steve Wesselingh
It has gone past the hour, and Eric's got a lot to tell us, so we'll start off and get the preliminaries out of the way, and then Eric can tell us about his amazing work.00:15 Professor Steve Wesselingh
Thank you for joining me for our second speaking of science webinar for 2026. Before I start, I'd like to recognise the traditional custodians of the lands which were gathered on. Today I'm speaking from Ngunnawal country in the ACT. I acknowledge their continuing culture and contributions paying my respects to elders past, present and emerging and to all Aboriginal and Torres Strait Islanders joining us today. I just like to remind you that at the end, we'll have a little bit of time for questions so if you have any questions, put them in the chat, and I can certainly give them to Eric. We're also recording this so that afterwards, if you want to watch it again, or you want to offer it to someone else to watch, please do that, and we also ask you to turn your microphones off during the webinar.01:11 Professor Steve Wesselingh
As I mentioned at our last Speaking of Science this year, our focus is on NHMRC investigator led discoveries that have made a real world impact on our national healthcare system. Now today's story falls within that category of discovery, through to impact, to the topic of oral disease.01:34 Professor Steve Wesselingh
Oral diseases such as tooth decay and erosion are the most prevalent diseases of humankind affecting nearly three and a half billion people worldwide. In Australia, the cost of treating oral disease and disorders is about $10 billion per annum, with the full economic impact of oral disease in 2010 estimated at $442 billion. Last Friday, the 20th of March, we celebrated world Oral Health Day to raise global awareness of oral hygiene, disease and prevention and the importance of caring for your mouth at every stage of your life. Early in the 20th century, the connection between fluoride and healthy teeth was discovered, and since the mid 20th century, water fluoridation and fluoride containing health care products have provided the mainstay of oral health treatment in many countries. However, over the course of the 20th century, evidence began to accumulate showing the consumption of dairy products too might lead to improved oral health.02:43 Professor Steve Wesselingh
That brings me to our speaker for today. After completing his PhD in 1978 at the University of Melbourne, biomedical researcher, Professor Eric Reynolds, AO began investigation into whether dairy products could provide a new and powerful method to treat and reverse tooth decay. Professor Reynolds now holds the position of Chief Executive Officer and Research Director of the Oral Health Clinical Research Centre at the Melbourne Dental School in the University of Melbourne. Professor Reynolds established the Australian Oral Health CRC in 2003 which is now the internationally recognised research centre focusing on major oral health disease. He was appointed an office Officer of the Order of Australia for his service to community dental health in 2005 and has received many accolades and awards for his contribution to dentistry with NHMRC funding commencing in 1989. Sorry Eric, I don't want to make you too old. The research activity of Professor Reynolds and his team have led to discovery of new dairy based technologies to help reduce oral disease.04:04 Professor Steve Wesselingh
I've heard Eric's name so often in regard to oral health over the last 20 to 30 years, but actually, I've never heard Eric talk. I'm really looking forward to Professor Reynolds' presentation today, and so please join me in welcoming to Speaking of Science today, Professor Reynolds.04:28 Professor Eric Reynolds AO
Thanks very much, Steve. A very kind introduction, and I hope I don't let you down. Thanks very much to all the audience that have joined in too. I really appreciate you joining the presentation.04:42 Professor Eric Reynolds AO
As Steve mentioned in the introduction, I've spent 30 years, and I do remember that Steve, 1989 was my first NHMRC grant Project Grant, and I can still remember it, because I'm very excited about it, and I get just as excited every time I get a new NHMRC grant. NHMRC has funded this work for 30 years, and so I have focused on dairy, and really this talk is about the important role of dairy in helping to reduce the major oral diseases. Steve mentioned tooth decay and erosion, but it also helps with periodontal disease. Gum disease, so I'll talk about that as well, which is relatively new, but quite an exciting area. But I'll start with, if I can get the slide to move, I'll start with tooth decay.05:56 Professor Eric Reynolds AO
The stats that Steve gave really show that it's still a major public health problem, and even though some of this data is a little old, we're looking at probably around one in two Australian 12 year olds that have tooth decay. It's defined as a pathological process of localised destruction of tooth tissue by microorganisms. This is bacteria in plaque and everybody knows that it's sugar in the diet that these bacteria ferment, and they produce lactic acid predominantly and other organic acids. You end up with a gel on the tooth, an acidic gel, because these bacteria will thrive in an acidic environment, and this literally dissolves the tooth mineral.06:48 Professor Eric Reynolds AO
The tooth enamel is hydroxyapatite based calcium phosphate base, and it's soluble in acid. The first signs of it you can see here are these white spots around orthodontic brackets, and there's severe forms of it with early childhood carries. It's related to sugar being used in a pacifier bottle, and you can see it's rampant destruction. But this slide here shows all the stages of dental carries, and it affects people of all ages, everyone with teeth, if they eat sugar and don't look after their teeth. You can see, from a healthy surface to the white spot, then it starts to discolour, and then you get destruction, cavitation. It does look like a significant problem, but I do want to go back.07:47 Professor Eric Reynolds AO
Steve mentioned fluorides. Fluorides were introduced in the late 70s, and if you look at the data before fluoride was introduced, you would see that nearly every Australian 12 year old had tooth decay, and the severity was much worse overall, than it is today, whereas there seems to be now high risk groups. As I mentioned, sugar in a pacifier bottle around orthodontic brackets, but you still see people if you don't look after your teeth, you don't clean them, you don't use fluoride, you can end up with with tooth decay.08:35 Professor Eric Reynolds AO
Going back to that 1989 NHMRC grant, I was really interested in how fluoride actually worked, and in the 90s too, the level of decay or the decline due to the introduction of fluorides, it plateaued. That was a major disappointment, because we were hoping that fluoride would, just it would just keep declining. But it did plateau, and then it started to be people like me, that question the mechanism of how fluoride was working and some people might remember the TV ads that, fluoride gets into the enamel and makes it resistant to decay. In actual fact, it doesn't make it resistant to decay, not enough fluoride gets into the enamel to do that. If someone stops using fluoride, stops drinking fluoridated water, or stops using fluoride products, and still eats sugar and has poor old hygiene, they get carries. Cildren that move away from a fluoridated area get carries, and there was a lot of questions about, how does fluoride actually work?09:48 Professor Eric Reynolds AO
As I mentioned, that acidic gel with lactic acid is dissolving the appetite base of a teutonem or releasing calcium. Calcium is calcium lactate phosphate is HPF, 4H 2PF 4OH, and so it just dissolves out. But interestingly, saliva, by producing calcium and phosphate, can remineralise, can put those ions back. But normally what happens, the challenge of demineralisation from the sugar in the plaque and acid produced overwhelms this process, so it continues to progress. But if you introduce fluoride, and if fluorides in the environment, what fluoride does is drive remineralisation, because fluorapatite is far less soluble than hydroxyapatite, even the same level of calcium and phosphate when carbonated, hydroxyapatite, which is a real tooth structure, is dissolving, you introduce fluoride into that environment, it will remineralise and put the mineral back.11:00 Professor Eric Reynolds AO
What we've shown is that it works in a catalytic way, because you very rarely get pure fluorapatite formed, that you get a fluorohydroxyapatite formed. You can see this, this is not a multiply. This is an x, and what we've shown is that it is never greater than point five, which means that you need 20 calciums for every fluoride ion to form this unit cell of fluorohydroxyapatite.11:33 Professor Eric Reynolds AO
This is when it dawned on us that obviously fluoride is becoming calcium limited, and it relies so much on saliva that if the saliva is hyperfunctional or not providing calcium. But as I said, even in normal saliva, it can be overwhelmed by the amount of sugar that's consumed in the diet and lactic acid that's produced. This was the early work where we showed that fluoride is calcium limited, and just to say that, more recently, we've seen in particularly in children and teenagers, where tooth decay and erosion are increasing and I put it down to two things. One is that it's become very trendy to drink bottled water that doesn't have fluoride in it, and so they're not consuming tap water that's fluoridated, and they consume these products that are loaded with food acids, particularly citric acid or citrate, because of the tangy taste, but disastrous for tooth enamel. You get a combination. You can have caffeine, which causes dry mouth, sugar and food acids in these drinks, they're disastrous for the dentition but even the ones that don't have sugar, be very wary of sugar free drinks and really, children shouldn't be encouraged to drink them because they have more food acid to to compensate for lack of sugar taste. Again, they're quite dangerous for teeth in terms of erosion. This really does show how important calcium is in the diet.13:29 Professor Eric Reynolds AO
This just shows you, here's a list of food acids that are commonly used, and this is really expanded in processed foods now in drinks and foods. I regularly go to the supermarket and look for these food codes. Unfortunately, people probably don't know what these codes refer to, but so many foods have these food acids that are removing calcium, and fluoride needs calcium to work. Even in Melbourne, with a major city where it's fluoridated, using fluoride toothpaste, it can get overwhelmed because there's not enough calcium to promote remineralisation.14:18 Professor Eric Reynolds AO
This is when I started to think about, where can we get a bioavailable form of calcium? I actually want to acknowledge one of my mentors in the dental school. When I first started as a researcher, introduced me to this study, and it really is a landmark study. It was done in Australia and published in 1967 in the Australian Dental Journal. It was a study on institutionalised children in Hopewood House in New South Wales, and they had really poor oral hygiene, but they were on a strict lactovegetarian diet, but they were allowed to eat as much honey and fruit and milk as they liked. But even though they're eating lots of honey, which is quite kerogenic, if poor oral hygiene, they got very little tooth decay until they left the house at age 12.15:24 Professor Eric Reynolds AO
You can see in the graph here, when they leave the house at 12, the carries rates just increase, just like non institutionalised kids in New South Wales. This was presented to me as a young researcher, by a mentor, that there were protective factors in milk, and a lot of research has been done in epidemiological surveys and laboratory work indicating that milk does have protective factors.15:59 Professor Eric Reynolds AO
You can see now, more recently, there's quite a few good surveys showing that consumption of dairy products and low fat dairy products are inversely associated with carries and periodontal disease. That's the second half of my talk I'll talk about that. The more recent studies, of course, are relating it to bioavailable calcium and casein phosphopeptides, and they're citing our earlier work, which I'm going to go back to.16:39 Professor Eric Reynolds AO
The funding I got from NHMRC in the 90s was to try and understand not only how the fluoride mechanism and how calcium and fluoride interact, but to try and systematically understand the mechanism of dairy in preventing tooth decay. Anecdotally, you know, milk buffers, and it's got calcium, which, interestingly, you know, after all these years of research, turns out that's quite an important part of how dairy does work. But with the NHMRC funding, we started to look at fractionating milk. We used various models, at that stage we used a rat carries model, where you put a typical organism like Streptococcus mutans, which is in human mouths and is associated with, particularly in children these high levels of tooth decay. If you put that in the rats mouths and put them on a sucrose diet, the good thing about rats is they quite love sucrose, and so there's no problem getting them to eat it, and they get rampant carries in a few months. It's a good model to test anti kerogenic agents with that model.18:03 Professor Eric Reynolds AO
But we also developed, and we were one of the first to do this, developed an in situ model where we would get human enamel, and we would make early lesions. You can see the white spots here that we've made. We would section and put half in an intra oral appliance, and then have volunteers wear these and they can use oral care products, or consume a normal diet. Then we can take out these enamel slabs and do microradiography, which is a very sensitive technique, and you can see the lesions here. We can actually see whether the lesions progress or regress. Regresses is remineralisation, progress is further demineralisation and what we showed was that the milk protein casein... So we separated, removed fat and showed that skim milk had the same anticariogencity as full milk, which is great. It wasn't related to the fat. We then did the old curds and whey, you know, separating casein from from whey. That showed that casein was superior, but it depended on how you made the whey, because if you make acid casein, a lot of the calcium ends up in the whey. But if you use rennet to produce micellar casein, then all of the activity that was in the casein calcium complexes. That's when we realised that it's related to this unique ability of milk casein to stabilise calcium and make it bioavailable.19:53 Professor Eric Reynolds AO
Of course, that's why dairy stands out, and it's designed to deliver bioavailable calcium to the developing neonate, and when it's digested, it releases these phosphopeptides that carry amorphous calcium phosphate into the gut, and it makes these highly bioavailable for absorption. By producing the casein phosphopeptides in the lab and then testing them with amorphous calcium phosphate, and I'm going to refer to this as CPP ACP from now on, we showed that all of the anti keragenic activity related to CPP ACP, and these are all the studies that were done in in the 90s with NHMRC funding and all published.20:47 Professor Eric Reynolds AO
Now, what's interesting about CPP ACP is when you look at the protein sequence, you see, here's the protein sequences of peptides, and these are the active regions, and they contain phosphoserines. This is SERP, you can see these clusters of phosphoserines, and these have evolved to carry nanocomplexes of calcium and phosphate, and stop calcium phosphate precipitating out, so makes it very bioavailable. What's interesting is that we showed that there's similar peptides in saliva. One's called stethrin, another a proline rich, but they're nowhere near as good as the milk sequence particularly these are from bovine because they need to carry so much calcium phosphate for the developing calf neonate. When you mix these with saliva, I say you're making a super saliva in terms of its ability to carry calcium phosphate and remineralise.21:58 Professor Eric Reynolds AO
But what's interesting is, when we looked at the sequences and the genes that encode these proteins are all from the same arm of the human chromosome four, and you can show that they've evolved from the same ancestral gene. They've evolved to solubilise and carry bioavailable calcium and phosphate. We spend a little bit of time actually analysing the structure of these using biochemical tests, solution phase NMR and electron microscopy. We've got a really good handle on..this just shows what happens. Calcium and phosphate ions in solution attract because calcium is two plus, phosphates three negative, they just keep growing and then ultimately fall out of solution. If these peptides are there, once they get to nanometer size, the peptides bind to them. This shows the peptide stick model.23:02 Professor Eric Reynolds AO
Here is a solid model where you can see the peptides completely encapsulate these calcium and phosphate clusters. In fact, with fluoride, it encapsulates a lot. Calcium phosphate fluoride. In these nano sized and electron neutral, and this is important in terms of their ability to fuse through plaque and into the nanoprosities of teeth. We've shown they actually do get into teeth and once they get into teeth, the peptides release the calcium phosphate, because they prefer to bind to crystal surfaces, and the calcium phosphate then is delivered to enable remin.23:46 Professor Eric Reynolds AO
This is now getting to 2000 where we managed to get NHMRC funding and industry backing to do quite an expensive randomised control clinical trial. The company was an American company, Warner Lambert, that made sugar free gum. They wanted to see whether adding CPP ACP to sugar free gum would be superior to sugar free gum without CPP ACP. You will know that, as I mentioned, fluoride in the water reduces tooth decay. Fluoride toothpaste reduces tooth decay. Well, consuming sugar free gum stimulates saliva, and that's been shown to have a positive effect in reducing tooth decay. It was a big ask to put CPP ACP in sugar free gum and show that it works. But that was the clinical study, and it involved 2720 school children in Melbourne, average age 12 and a half years. They were provided with a fluoride toothpaste. They all consume fluoridated water and they were randomly assigned to sugar free gum with CPP ACP, or a control sugar free gum, which was exactly the same, except didn't have CPP ACP.25:09 Professor Eric Reynolds AO
They chewed the gum three times a day, or they were asked to anyway, chew the gum three times a day for 24 months. I won't go into this, but we developed at this time, it was really state of the art now it's pretty common, but we developed standardised digital radiography at baseline in 24 months. That gave us the ability to do a carries progression regression analysis using a transition matrix. This just shows the radiographs and you see we put a step wedge, which enabled us to ensure the contrast baseline and 24 months was the same to do the comparison. Just to show you, this is one of the children at the start. These white areas here are fillings. You can see this child was carries risk as prior evidence of carries. If you see this shadow here, and it's in a proximal space here, between teeth where you get plaque, you can see there's carries developing here, and this is usually what happens, you get occlusal carries in a proximal and this then combines into a big filling.26:26 Professor Eric Reynolds AO
But what happened is 24 months later, no new carries, and that lesion is gone. This is one of the children on the CPP ACP that's actually remineralised that early lesion. Here's the results, once they were decoded and statistically analysed. This is the transition matrix. We can see regression. The CPP ACP gum produce 53% more regressions than the control gum. It really shows, and this is why I use the term super saliva, by putting CPP ACP in saliva, you enhance its ability to remineralise enormously, and particularly because these children were in a fluoridated area, you then get the synergistic effect of CPP ACP and fluoride.27:20 Professor Eric Reynolds AO
What we saw in terms of slowing the progression of carries, we slowed it by 20%. I mentioned to you that toothpaste is considered to reduce carries by 14 to 20% this is one of the early studies that was looking at fluoride toothpaste against a controlled toothpaste, and this is children that weren't in a fluoridated environment, so not consuming fluoridated water. This is a controlled toothpaste, effectively, no active in it. What they showed in 24 months is virtually the same protocol. They got a 20% reduction, or 20% slowing in progression of carries.28:11 Professor Eric Reynolds AO
That does put it in into context, given that we were looking at CPPACP against sugar free gum that's been shown to reduce carries, fluoride toothpaste which is reducing caries and fluoride in the drinking water. It really does highlight the additive effect of calcium, providing that by available calcium in a fluoride environment. All our research indicated, this clinical trial really confirmed and validated that if you provide bivailable calcium for fluoride, you get a enhancement in reduction of carries.28:53 Professor Eric Reynolds AO
By this stage, we had our first Oral Health CRC, and the CRC funded a lot of the commercial activities. We used NHMRC for the basic studies, to look at mechanisms, etc, and understand what was going on. The CRC funded most of the commercialisation, but there was a company that then developed the first product with CPP ACP and fluoride, and this is just actually getting volunteers to use the product. Then we collected saliva after they used it and if you see, if you use a placebo toothpaste with no fluoride or calcium and phosphate, you get no fluoride in saliva and very little fluoride in saliva and very little calcium and phosphate. But when you use the CPA ACP product, you can see the levels of bioavailable calcium phosphate in saliva are huge, you know, sort of more than 15 times greater. But what is absolutely fantastic is that you get fluoride as well as bioavilable calcium phosphate.30:17 Professor Eric Reynolds AO
Now, without the peptides, this would all crash out. Fluorapatite is very poorly soluble, and it's the peptides that are delivering not only calcium phosphate, but also fluoride. This is what's critical with these products. It's making it bioavailable, and it's presenting it in saliva. When we used our in situ model, this is exactly what we saw. In fact, this was the first study when we realised the dramatic effect of making bioavailable calcium phosphate available with fluoride.30:54 Professor Eric Reynolds AO
The other exciting thing is, these are transverse microradiographs, so that's the surface and that's the advance in front of the lesion. You can see fluoride, by itself, is very reactive, and it reacts with the surface and forms most of its fluorapatite in the surface. But when it's incorporated into these electron neutral complexes, the peptides, by being nano sized, deliver it right through and we get remineralisation right through the lesion. We're getting, and I'll show you, it's fluorappetite.31:31 Professor Eric Reynolds AO
We can do transmission electron microscopy of thin sections, and this is demineralised, where you can see the inner prismatic spaces between the prisms and rods, the structure of the enamel are dissolving, and all these little donor appetite crystals that dissolve from the centre first, because this is where all the carbonate is. After remin with CPP ACP, and this is in the body of the lesion after remin with CPP ACP and fluoride, which we refer to as CPP ACFP, you can see that most of the donuts are remineralised. Even the interprismatic space is remineralised and it enables us, you can do then electron diffraction. It showed we're actually forming fluorapatite, not fluorohydroxyapatite, but we're actually getting fluorapatite.32:28 Professor Eric Reynolds AO
The reason being is because the Nano complexes provide calcium phosphate and fluoride in exactly the right molar ratio to form fluorapatite. That's the way we prepare the CPP ACP in the fluoride. The molar ratio in the Nano complexes is the same as fluorapatite, and that's what forms in the body of the lesion.32:54 Professor Eric Reynolds AO
Now the product's been commercialised, and these products are in available in over 50 countries. There's been a lot of research on them, and if you put CPP ACP into PubMed, you know quite proud that Australian technology now has 800 publications all around the world, with people analysing these products, confirming that they do in factory mineralise.33:22 Professor Eric Reynolds AO
In fact, there's enough clinical studies now for systematic meta analysis, and there's more than 15 independent systematic meta analyses. These are all independent. They're listed here. Just showing some of the clinical cases, a lot of them are after orthodontic D banding. You can see the white spots, and this is just after a couple of months of CPP ACP, and this is a hypermineralised case where the stain was polished off, and then CPP ACP, so it's just polishing. Then using the CPP ACP for a couple of months, and you get significant remineralisation and this is an American study where they were looking at it during orthodontic therapy. Though they showed that the CPP ACP completely stopped demin around the brackets, and in the placebo group, they got significant demin around the brackets. But why I included this particular photo is because they said it not only stopped demin around the brackets. You see, these white area at the sizal edge which is quite typical in children. The incisors, when they erupt, they have a hyper mineralised edge and that hypermineralised edge over the period of a few months, remineralised. They said it not only stopped carries, it actually mineralised the hypermineralised incisal edge. That was a study done in the US.35:12 Professor Eric Reynolds AO
Now you can imagine, through all this work, all the major oral care companies have realised the importance of calcium, so they all add some form of calcium now to their products. Amorphous calcium phosphate is largely the same as what's with CPP, but it's not stabilised. That's probably the best after CPP ACP, but it's difficult to stabilise, and it can precipitate out intraorally, which you don't want. The other products, calcium phosphorsilicates, effectively a calcium glass, releases calcium quite poorly. Calcium carbonate, which is added, a lot of toothpaste companies use calcium carbonate, but again, solubility is very poor. But look, they all work to an extent.36:07 Professor Eric Reynolds AO
This is a graph that we did to look at do they enhance fluoride's remineralisation, and they all do. They are certainly worth using. But you can see the one that stands out is because this is got the highest level of soluble calcium in saliva, so it's bioavailable, and it really helps drive fluoride remineralisation.36:36 Professor Eric Reynolds AO
Okay, so now I'm going to get on to periodontal disease, because we've also spent a fair bit of time on that with NHMRC funding. It's a little bit of a different aspect, but it's interesting how things all come together. My interest in periodontal disease was trying to understand the microbial aetiology. Because it was very complex, and as new techniques became available, particularly the ability to analyse plaque samples for the microbial community, using next gen sequencing, really opened up the field. I've always been very interested in it and so I'll just tell you the story on this and how it's now interacting with CPP ACP.37:31 Professor Eric Reynolds AO
The periodontal diseases, major diseases, mainly of adults, but you can still see gingivitis, on the left. They're defined as chronic inflammatory diseases associated with microorganisms in plaque. In children, it's largely super ginger plaque, and you can see here chronically inflammed. The good thing about gingivitis is that if you can motivate the person with gingivitis to clean properly, to floss, which is very important, to get the plaque out and to clean these areas, the inflammation resolves and there's no lasting tissue destruction.38:21 Professor Eric Reynolds AO
But the difference with periodontitis is that you get a pocket. What happens if gingivitis goes unchecked, this swelling causes a pocket, and then you start to get emergence of gram negative bacteria, and particularly gram negative protolytic obligate anaerobes that are very nasty, and you end up with tissue destruction. This is a probe that's the same length as this one. It's going all the way down to here. You have someone that looks... there's no gingivitis here, but they've got periodontitis and substantial tissue destruction and loss of the supporting bone. This shows it with recession, and that's what this would look like if the soft tissue wasn't there.39:18 Professor Eric Reynolds AO
We're seeing about one in three adults have moderate to severe periodontitis. Recently, it's been reclassified clinically. It's always been gingivitis, early to moderate periodontitis and moderate to severe periodontitis. It's been reclassified as stages of disease. Stages one and two for early to moderate, and stages three and four from moderate to severe. What I was really pleased with was that the stage three to four was around pocket depths. That's a PD down here. Pocket depths of six millimetre or greater. Our research showed that it's these pockets where these proteolytic gramme negative pathogens emerge, and it ultimately becomes an infection. I was pleased to see that the clinical classification met our microbiological transition data, and others have shown this as well.40:42 Professor Eric Reynolds AO
These microbiome studies, we've done them. Others have done them. This is a big study that was done in the US, but probably can't read this, but I'll show you later. But the greener, what we know as commensal, and in fact, now we know they're beneficial species like rothia species, the middle strep. These are not the kerogenic strep, these are the ones that are associated with health. Karine bacteria and actinomyces, these are the gramme positive species that you see typically in someone with a really healthy dentition and healthy periodontal tissue. These are the species that you see emerge down the base of these deep periodontal pockets. Porphyrmonas gingivalis is now considered a keystone pathogen. It loves being down the base of a pocket, and it has partners in crime in terms of spirochetes. This treponema denticola spirochete, the two together, they produce a very pathogenic consortium, okay?41:55 Professor Eric Reynolds AO
This just shows a study that we've done when patients are treated with disease, what happens is that the plaque down the pocket is removed by scaling and root planing, and many sites respond to that, and you get resolution. The inflammation resolves, and there's no progression of disease. However, even with professional treatment and on a professional maintenance programme, you still see sites progress. We wanted to understand what is it about these sites that progress, so we did a progressive study. When a site progressed, we went back and looked to see what was in that site, and the key culprit was porphyromonas gingivalis with its partner treponema denticola. But you can see, if you had more than 15% of the consortium down the base of the pocket is P gingivalis. You got 100% chance that site's going to continue even after treatment.43:06 Professor Eric Reynolds AO
Now there's a lot of research that has been done on the link with the severe forms of periodontitis with a variety of things. It's not good to have chronic periodontitis, where people can get these infections in their 30s, and it increases the risk... The Diabetes link goes both ways and increases the risk of cardiovascular disease, preterm and low birth weight. It's linked with chronic inflammatory diseases like arthritis, certain cancers, like oral pharyngeal cancer, and more recently, cognitive impairment. I'll touch on that, because we've been involved in that, in its link with Alzheimer's.43:56 Professor Eric Reynolds AO
Now I'm going to have to move on, because I just noticed the time ticking away. This just shows a study we did that was published in Science Advances in 2019 that this organism, P gingivalis, we can find it. These are brain specimens from deceased Alzheimer's patients, and we found that the P gingivalis, proteases associated with amyloid plaque and tau tangles are hallmarks of Alzheimer's disease.44:34 Professor Eric Reynolds AO
The person I collaborated with went off and formed a company in the US and developed a drug and showed that this drug in Alzheimer's people with P gingivalis infection, which is about 30% of the cohort, they had, 37% they showed the treatment of the drug targeting P gingivalis protease, reduced cognitive decline by 57% and it's quite a remarkable reduction. It also suggests that about a third of Alzheimer's may be linked with chronic periodontitis, associated with these nasty pathogens.45:16 Professor Eric Reynolds AO
Alright, what I'm going to show you, very quickly, because I'm running out of time, is that we don't think you need this drug. I mentioned sites that progressed, but sites that the treated that resolve, we've now analysed them, and we've got a good handle on why they resolve. Not only do you see a reduction of the pathogens, you know, porphyro gingivalis, treponemogenicola in the pocket. This is more significant to me. What we see is they get replaced with these beneficial bacteria, karine bacteria, actinomyces, the middle strep, etc. We're replacing pathogens with beneficial species and as epidemiologically dairy products, low fat dairies, again, being linked with with reduction in periodontal disease.46:10 Professor Eric Reynolds AO
This is a huge study in Denmark that really got my interest, because they were looking at severe periodontitis, and this is taken from this study. I added the CPP ACP. But apart from that, it's exactly from this study. Intakes of calcium and casein were inversely associated with periodontitis severity, and they adjusted for age everything. It's a really well conducted study. It was pretty conclusive, and to me that says CPP CPA is doing something they didn't know what... But sorry, they knew it was reducing periodontal disease, but they didn't know the mechanism.46:52 Professor Eric Reynolds AO
Now we've been doing some work at that stage on regular use of CPP ACP, and we find that it actually modulates the oral microbiome and not only are some other people showed that regular use of the CPP CPA products, you see changes in the oral microbiome where you're seeing increases in beneficial species. We wanted to see, is it actually a prebiotic? Is it promoting beneficial species and therefore reducing disease? We looked at gingivitis, we did a dose response, and I'm going to have to whiz through it, unfortunately. The conclusion was the clinical trial, when it was decoded that we saw a significant dose response. All of the people had professional cleaning so this is why you get a reduction in gingivitis when you get a professional clean at the dentist. We expected that, but we didn't expect this significant dose response reduction of gingivitis.48:04 Professor Eric Reynolds AO
Then we look at the microbiome, and we can see what we're seeing, this is a reduction, and these are increases. The reduction all gramme negative anaerobes, and the increase is gramme positive. These are the major reductions, all gramme negative. The prevotella, the tenurella and the selena monus are all obligate, highly proteolytic and associated with with quite severe periodontal disease. But all of them are gramme negative and produce LPS that is inflammatory.48:43 Professor Eric Reynolds AO
When we looked at what CPP CPA is increasing that takes their place, it's all gramme positive organisms, the ones I mentioned, actinomycetes, rothia, karenia bacteria and the streps. These all have either arginine deiminase or nitrate reductase, and some both. We then went back and looked at all of the samples and all the species, and we showed a clear dose response reduction in gramme negative species and a clear dose response increase in these gramme positive beneficial species with arginine deiminase and nitrate reductase.49:21 Professor Eric Reynolds AO
I'll skip over. Why are these gramme positive organisms? They produce interesting structures, I talked about. You see them in thin biofilms in healthy people, and they produce structures which I haven't got time to go into, which stops the pathogens colonising. There's some really nice work showing that the nitrate reductase species, if there's nitrate there, they produce nitrite and nitrite kills all of these periodontal pathogens. It also kills the kerogenic ones like strep nutans Then the good streps produce hydrogen peroxide, which kills the gramme negative pathogens as well. You can see this antagonism, if you get a healthy biofilm, it really does help protect against oral disease.50:16 Professor Eric Reynolds AO
What we've shown, how does CPP ACP do this? It does it by improving the fitness of these beneficial species we've shown. It gets into plaque, and this is the black dots, and these are the commensal species. It buffers, because it's got very high buffering capacity, and it maintains oral pH homeostasis, which is very important for the commensals.50:42 Professor Eric Reynolds AO
Interestingly, we've shown it's got a half life of about one to two hours, where these bacteria break it down and take up the peptides and they use it as a nitrogen source. Minor acids like arginine, lysine, glutamine, asparagine, and similar to what's been shown in the gut, the CPP are rich in prebiotic amino acids. Again, going back to this is dairy, this has evolved to produce homeostasis, and there's a prebiotic in the gut. It's not too surprising. We're seeing it in the mouth as well. We're seeing an improvement in fitness, and these species then out compete the pathogens, and that's what we believe is a mechanism for reducing periodontal disease. The commensal species also stimulate anti inflammatory, FOX P3, plus T reg cells, so there's an element of immune tolerance and mucosal homeostasis with these beneficial bacteria as well. The very important bacteria for the development of oral homeostasis.51:58 Professor Eric Reynolds AO
I am finishing now, Steve. This comes back to, well, if dairy is enhancing nitrate reducing species, where are they getting their nitrate from? Well, of course, nitrate comes from vegetables, particularly green leafy vegetables. There's many vegetables at a rich source of nitrate. If the CPP ACP is promoting the nitrate reducing, you'd expect to see some additive effect between dairy and vegetables. Well, that goes right back to the Hopewood House Study, which was a lacto vegetarian diet. Since then, there's been a number of studies. This one's a study in the gut, and as I said, what happens in the gut we're showing happens in the mouth as well, exactly the same. You can see a lacto vegetarian diet here is producing a better effect than just a vegan diet, as opposed to omnivorous. But these other studies looking at oral health and promoting a healthy oral microbiome, it does really show the importance of dairy and vegetables. I'm finishing saying that a lacto vegetarian diet is very good for oral health.53:31 Professor Eric Reynolds AO
The CPP ACPs are also used clinically to reduce sensitivity. I just mention that because a lot of dentists use it clinically to reduce sensitivity, and patients can use it at home as well. Because it remineralises so well, it blocks these tubules. These are tubules of root surface that become exposed and cause sensitivity. This shows electron microscope where you see CPP ACP completely covers it and this is a high magnification where you can actually see the peptides I quite like.54:05 Professor Eric Reynolds AO
This is a big clinical trial done overseas showing significant reduction in tooth sensitivity. I'm finishing this is why CPP CPA is used around the world because it not only helps reduce the risk of tooth decaying erosion, it actually helps with periodontal disease, but it helps reduce dental sensitivity, but it actually can even improve the appearance. Here we can see some hypermineralised areas and some stain and this is literally after polishing and in surgery, bleaching, and then a few months of CPP ACP, the peptides bind water. They're better than saliva at that and so you get this glossy appearance. They mineralise and the mineralising enamel, stops the dentine showing through that yellow colour, so that appears much whiter. There's a lot of dentists in Australia now that use this, and that's why originally the first product was called tooth mousse, because it's a conditioner for your teeth. Not only remineralises it improves homeostasis.55:25 Professor Eric Reynolds AO
I wanted to acknowledge NHMRC, that have funded this for 30 years of research, and also the Cooperative Research Centres Programme. We've had two of those that's helped with the commercialisation. Of course, the people, the core researchers that have done this, Pieyen Shen, James Fernando, Coralie Reynolds, Yi Yuan and Jeff Adams. I also want to thank Mike Morgan and Denise Bailey that assisted with some of the particularly big clinical trials, and Stuart who assisted with the microbiology.56:01 Professor Eric Reynolds AO
Sorry, I took so long, Steve, but you got the whole talk.56:08 Professor Steve Wesselingh
Thanks very much. That was fabulous, and such an important story, right from the beginning of that first trial all the way to where we are now. Incredible story, thank you very much. I'll just say to everyone, we haven't got a lot of time, but if you do have a question, throw it into the chat and we'll see if we can use it. Eric, my question is that, and it really is to all of us as people with teeth, we want our teeth to be as good as possible. What is the best source of CPP ACP that we can have? Is it dairy and yoghurt, or is it actually buying a product off the shelf and utilising it? What's the best thing the average healthy person should be doing?56:56 Professor Eric Reynolds AO
Well, that's a good question. Yes, you do get it in dairy, but the oral care products, it's highly concentrated. One of the unfortunate things about getting it from dairy is it's expensive. It's the oral care products with CPA ACP that end up being the most expensive. But, and I thought Steve commercially that would kill it. But what staggers me is that people around the world, because of the benefit, and particularly dentists are aware of it, strongly recommend it, that people will pay three times the price of products that don't have it.57:38 Professor Eric Reynolds AO
But if you can't afford it, then low fat dairy products, definitely low fat for health. The products I put up they are all the ones that we consume at home. Low fat milk, the low fat yoghurts are delicious. But I have gone off cheese, unfortunately, just because I had to get my cholesterol down. I love cheese, and cheese is a really good source because of the CPP ACP, but unfortunately, there's just too much fat in cheese, so I can't have it. I don't want to mention the products, but I use them. My family use them every day and I would recommend you can in Australia, you can get them at any chemist or supermarket.58:43 Professor Steve Wesselingh
That's one of our questions. Can we buy the oral care products, toothpaste and gum, at the supermarket or the chemist?58:51 Professor Eric Reynolds AO
The product that's in the supermarket, chemist in Australia, is called tooth moose, the one with fluoride. I strongly recommend tooth mousse. Plus tooth mousse is only for children, really six years or younger, so they don't ingest the fluoride. But tooth mousse is not a toothpaste, so it doesn't have detergents, doesn't have abrasives. You can use it, and I recommend that people use it. You put it in your mouth, distribute it around with your tongue and leave it in your mouth for 15-20, minutes, or as long as you can. The longer the contact time, the better effect. That helps, and that means you only have to use a small amount to help offset the high price for it.59:39 Professor Eric Reynolds AO
That's the best way to use it so. What I recommend is you rinse with with water, you floss, you then use a good quality fluoride toothpaste, and then use tooth mousse plus. But you don't spit it out in 30 seconds. You keep it in your mouth for 15-20 minutes, or as long as you can. It's completely safe, and then spit out, and you enhance contact time. Remin is dose and contact time related so the longer the contact with the tooth enamel, the better remin you get.1:00:19 Professor Steve Wesselingh
We have a couple of other questions here. Would it be more effective to add fluoride to dairy products rather than to water?1:00:27 Professor Eric Reynolds AO
Well, that was done. Interestingly, when it was first done, that's a very good question, because when it was first done, because the fluoride incorporates into the calcium phosphate complexes in milk, that was considered not a good thing, because you need fluoride ion. But what we've shown actually that it is a good thing. You could definitely add fluoride to milk, and you get the benefit of calcium and fluoride, and we've actually done that. The person who asked that question.... That's a very good question, because adding it to milk makes milk far better in terms of reducing tooth decay, right?1:01:14 Professor Steve Wesselingh
Well done. Richelle, well done.1:01:17 Professor Steve Wesselingh
Joe has asked, and I'm sure you are asked to defend or advise on the level of fluoride in water. We know there are councils in Northern Queensland who are now stopping fluoridation and so this must be something that worries you.1:01:34 Professor Eric Reynolds AO
It does indeed. As you said, and as I said, you know it has such an effect because brushing your teeth or using CPP ACP and fluoride products relies on compliance, whereas having it in the drinking water and children drinking the water means that you're getting fluoride benefit to them. That's why fluoride in the water is so effective at reducing dental carries and I said that all we have is our results and other people show that the major reduction we've seen in Australia is through fluoride in the drinking water. I am concerned about any push to remove it. It is a real backward step, in my opinion,1:02:23 Professor Steve Wesselingh
My last question. I noticed on one of your first tables, you had the list of acids that people are consuming, particularly in high energy drinks, etc. But one of the acids was ascorbic acid, which obviously is in fruit and particularly oranges and other things. I mean, obviously ascorbic acid has a whole lot of positive benefits. How bad is it for your teeth, and how bad are fruits and oranges and juices?1:02:52 Professor Eric Reynolds AO
Well it was way down on the list from memory, it is not a bad guy. It was the ones up the top that are the bad guys.1:03:01 Professor Eric Reynolds AO
No, it's not significant in terms of erosion. Look at ascorbic acid, my concern would be, if you're chewing ascorbic acid tablets, you know that you can buy these mega vitamin C tablets that are all ascorbic acid and I would be concerned if you're doing a Linus Pauling and chewing 20 or 30 of these a day. You could definitely then cause erosion. But for the normal person having one a day, or two a day, or something like that, that is not going to do anything to the teeth.1:03:41 Professor Steve Wesselingh
Alright. Well, we might end there. I really want to thank you for a fantastic presentation, incredible science, but actually science that has gone from the discovery science all the way to products that are important to all of us, because everyone has teeth.1:03:59 Professor Steve Wesselingh
As you've said, there are so many health... Not only don't we want bad teeth, but bad teeth are associated, as you said, with cardiovascular disease, your work on dementia was really interesting and so just incredible work. I think everyone here at NHMRC should be pretty proud that we've funded you to do this work and we really like to see this sort of pathway from discovery to translation, so thank you. Thank you very much and congratulations to you and your team.1:04:32 Professor Steve Wesselingh
I would like to thank everyone who joined us on the talk and also the really high quality questions, and encourage everyone to come back to the next webinar. So thanks, Eric, that was fantastic.1:04:45 Professor Eric Reynolds AO
Thank you. Thanks everyone.End of transcript.