Perspectives

Healthy mouth, healthy body: Are dental caries the harbinger of metabolic disease?

Sarah Hancock, Cliff Harvey

Received: 31 May 2025; Accepted: 03 Aug. 2025; Published: 22 Sept. 2025

Copyright: © 2025. The Author(s). Licensee: AOSIS.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dental caries is an easily identifiable marker of poor metabolic health. The proposed model of dental caries aetiology portrays the caries process as both a local response and systemic hormonal and metabolic responses to diet-driven mitochondrial dysfunction and metabolic dysregulation. The prevention of dental caries through the life course should become a global healthcare priority and may assist in the prevention of chronic disease through the lifespan.

Keywords: dental caries; metabolic health; refined carbohydrates; vitamin deficiency; oral health.

Introduction

In the 19th century, Antoine Bechamp and Louis Pasteur debated the origin of infectious diseases, which were the leading causes of death at that time.¹ Bechamp advocated for ‘terrain’ theory, which posited that disease occurs in a vulnerable host with a dysregulated cellular environment. Pasteur promoted an alternate ‘germ’ theory, characterised by reductionist approaches which focused on the role of microorganisms as causative of disease. The application of the ‘germ theory’ framework towards the end of the century resulted in the establishment of public health strategies, including sterilisation, sanitation, vaccination and the formation of food guidelines and educational hygiene programmes.¹ Consequently, the germ theory paradigm became the dominant framework for the management of all disorders within healthcare systems.²

The assumptions of the germ theory paradigm have been applied to non-communicable, non-infectious ‘lifestyle’ disorders, which are currently the predominant causes of morbidity and mortality worldwide.² A central tenet of germ theory is that management of chronic non-communicable diseases (NCDs) comprises the suppression or elimination of pathological targets of blood glucose levels, cholesterol and other lipids, mutations, and abnormal protein aggregates for metabolic syndrome, atherosclerosis, cancer and neurodegenerative disorders, respectively.² However, the prevalence of these disorders has increased over recent decades, and current approaches do not consider underlying diet-related metabolic and hormonal processes at cellular levels that are implicated in health and disease.

In recent times, dysregulation of mitochondrial function leading to systemic inflammatory processes and compensatory hyperinsulinaemia has been identified as central to the aetiology of chronic diet-related diseases of predominantly adult onset.² Typically, the first marker of metabolic dysfunction during the life course is regarded to be high fasting blood glucose levels or prediabetes as a consequence of prolonged hyperglycaemia and increased insulin resistance.³

The most prevalent chronic disease globally is dental caries, which affects more than 3 billion individuals across all age groups. Incongruously, dental caries and other aspects of dental health remain largely overlooked in the metabolic health literature.⁴ In a recent study in which the connections between a range of NCDs were modelled using a complex network approach, dental caries was found to be the most frequently co-occurring NCD across all age groups; an escalation was observed in the quantity and diversity of connections to other NCDs with increasing age.⁵ Further, by 20 years of age, dental caries is associated with periodontitis, which in turn was connected in the network model to metabolic risk factors.⁵ Unlike NCDs traditionally associated with adult-onset, dental caries in young people is an early, painful and rapid demonstration of the harmful effects of a poor-quality diet. In children of pre-school age, dental caries can necessitate the extraction of multiple teeth because of the severity of the disease presentation.

The caries process begins with the appearance of reversible lesions on the surface of the teeth in response to acid production from the fermentation of carbohydrates by oral bacteria. In addition, a series of unmitigated hormonal and metabolic responses leads to systemic inflammation at cellular levels that results in non-reversible destruction of teeth.

Dental caries: A metabolic disease

Traditionally, dental caries is regarded as the destruction of dental tissues by acids generated by the metabolism of fermentable carbohydrates by bacteria on the tooth enamel.⁶ However, considering the dental caries process using only the local ‘in-mouth’ reactions to carbohydrate metabolism ignores other evidence regarding mitochondrial dysfunction, metabolic dysregulation and systemic inflammation in the development of dental caries. Importantly, considering how the hypothalamus–parotid axis controls hormone secretion in response to a modern dietary lifestyle may show dental caries to be a metabolic disease underpinned by cellular dysfunction.

To understand how a dietary pattern comprising restriction of refined carbohydrates enables optimal oral health, some historical context is required. Given that much of the evidence regarding dietary patterns over time is derived from anthropological studies of the oral microbiome, what follows is a brief outline of how dietary shifts over time produced transitions towards eating patterns implicated in dental caries and the presentation of a proposed dual process model of dental caries aetiology.

Dietary transition: From hunter-gatherer to modern dietary lifestyles

The first principal alterations in the oral microbiome involved the shift from hunter-gatherer diets during the Neolithic era to carbohydrate-based diets.⁷ There were marked increases in the prevalence of calcified plaque, changes in the composition and diversity of the oral microbiome, and evidence of dental caries. Notably, caries and other oral diseases, including periodontal disease, occurred rarely in pre-Neolithic societies, and the appearance of oral disease was attributed to the increased consumption of cereals in this era.⁷

Dr. Weston Price’s investigations into indigenous populations revealed that the shift from traditional diets to processed foods correlated with a marked decline in oral and systemic health. Price attributed this deterioration in oral health and the emergence of chronic illnesses to the adoption of ‘displacing foods of modern commerce’, including white flour and sugary products.⁸ Historical patterns surrounding World War II suggest a link between processed carbohydrate supply and chronic disease incidence. The rates of both oral and chronic disease increased and decreased over this time in alignment with the availability of refined carbohydrates. Notably, diabetes-related mortality among English women decreased by 29%, and dental caries in young British schoolchildren decreased by 28%.⁹ These patterns suggest temporal associations between reduced consumption of processed carbohydrates and improved health outcomes.

Currently, the dietary patterns of humans in developed and developing countries consist of a high intake of refined carbohydrates from ultra-processed foods (UPFs) and multiple daily eating occasions characterised by between-meal snacking.² The high consumption of grain-based processed foods adds to high carbohydrate loads, which leads to leptin dysregulation and cycles of increased hunger.¹⁰ The increased frequency of food intake means that substantial parts of the day are spent in a postprandial state typified by constantly high levels of substrate, prolonged glucose elevations and over-proliferation of unstable advanced glycation end-products (AGEs).¹⁰ Sustained activity of glycolysis, coupled with subsequent pyruvate oxidation and the citric acid cycle within the mitochondria, can lead to a high production of nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FADH2). If the electron transport chain’s capacity to process these electron carriers is exceeded, it could potentially result in electron overflow. High-frequency, chronic overfeeding leads to the initiation of hormonal and metabolic responses to mitigate mitochondrial exposure to oxidative stress; the most prominent response is compensatory hyperinsulinaemia and peripheral insulin resistance.³ Another response is represented by a set of reactions in which changes in the hypothalamus–parotid axis control of parotid hormone secretion result in alterations in the flow of dentinal fluid by which teeth are nourished internally.¹¹

The aetiology of dental caries

Traditionally, and aligned with the germ theory of dental disease origin, the development and progression of carious enamel lesions is viewed as a local within-mouth series of reactions that are initiated by the ingestion of fermentable carbohydrates. This pathway is outlined in Figure 1.

FIGURE 1: The traditional aetiological model of dental caries.

On ingestion of fermentable carbohydrates, bacteria, including Streptococcus mutans, Bifidobacteria, Atopobium, Propionibacterium and Lactobacilli, metabolise carbohydrates and produce acids.¹² The oral biofilms become increasingly acidic; critical pH levels for enamel demineralisation range between 5.0 and 5.5 and are dependent on salivary flow and food consumption frequency.¹² At early stages of enamel demineralisation, the caries process can be arrested or remediated via the uptake of calcium, fluoride and phosphate from saliva.¹² Mechanisms by which saliva also enables protection from caries include: the clearance of food particles from the mouth; acting as a buffer for neutralising acid; and maintaining supersaturation of tooth minerals.¹² The development of enamel lesions within the mouth and progression to cavitated lesions is a reflection of the net effect of demineralisation of tooth surfaces by the metabolism of fermentable carbohydrates by bacteria and remineralisation of teeth through saliva production and dietary behaviours involving food consumption frequency.

Evidence from animal studies suggests that a high-frequency intake of refined carbohydrates exerts a significant influence on dental tissue nourishment via a pathway mediated by the hypothalamus–parotid axis.¹¹ The nourishment of the non-vascularised dentine is facilitated by a centrifugal fluid flow through the dentine and enamel.¹¹ This process is driven by the secretion of parotid hormone from the parotid gland and, comparable to the secretion of insulin by the pancreas, is a process that is regulated by hypothalamic activity.¹¹ High levels of blood glucose lead to increases in the metabolism of the mitochondria in the hypothalamus and increased production of reactive oxygen species (ROS) resulting in increased inflammation. Simultaneously, the hypothalamus downregulates parotid hormone secretion and upregulates insulin production from the pancreas.¹¹ The downregulation of parotid hormone secretion leads to a reversal or cessation of the centrifugal flow of dentinal fluid and tooth malnourishment.

The dysregulated metabolism within the hypothalamus and continually increased production of ROS and hypothalamus-based inflammation promote insulin resistance in skeletal muscle, fat, and the liver.³ The compensatory upregulation of insulin production by the pancreas to maintain stable blood glucose causes hyperinsulinaemia,³ which is implicated in multiple inflammatory conditions, including periodontal disease, and in metabolic diseases, including type 2 diabetes, neurological disorders, vascular disease and some cancers.³ Hyperinsulinaemia is also associated with dysregulated leptin function, which regulates food intake and energy balance by signalling satiety from food consumption.¹⁰ The consequence of leptin dysregulation is the promotion of increased hunger, leading to excess food intake and consequent weight gain.¹⁰ Deficiencies or insufficiencies of Vitamins A, D and K2, calcium, iron, and zinc are also implicated in immune-inflammatory modulation, metabolic dysregulation, and poor tooth and bone health.¹⁰ Poor vitamin D status in particular is associated with both periodontitis and dental caries in children.¹³ The mechanisms by which Vitamin D deficiencies impact oral health include altering dentine and enamel development in utero, resulting in enamel hypoplasia, decreasing activation of antibacterial peptides such as cathelicidins and defensins, and reducing calcium ions in saliva.¹³

The model of the dental caries aetiology presented in Figure 2 provides a compelling case to reconsider the paradigm of dental caries progression. Further, the action of multiple bacteria within the mouth and metabolic and hormonal processes occurring at cellular levels illustrate a dual response to a high-frequency intake of refined carbohydrates. Similar to the model outlined by Phillips,² dental caries is a culmination of responses to a diet-related disorder of mitochondrial dysfunction.

FIGURE 2: The proposed pathways and mechanisms of dental caries and chronic disease.

Taken together, a persistently high intake of refined carbohydrates and dysregulated hormone-mediated responses originating in the mitochondria of the hypothalamus are central in the development of chronic diet-related diseases, including dental caries. Given the prevalence of dental caries within the general population, particularly young children of preschool age, the presence of dental caries is an easily identifiable marker for underlying metabolic dysfunction. As such, dental caries should be regarded as one of the earliest indicators in the life course of cellular dysfunction and systemic inflammation in response to the excessive intake of refined carbohydrates.

Children with dental caries are at increased risk of poor oral health persisting into adulthood. The development of caries in both deciduous and permanent dentitions is particularly concerning, as the condition is inherently lifelong, progressive and cumulative in nature.⁵ Nonetheless, oral health remains insufficiently addressed within public health nutrition, especially in the context of dietary strategies aimed at preventing chronic disease. This oversight is disconcerting, given the common risk factors underlying both dental caries and chronic diet-related health conditions.

Prevention of dental caries

The concept of dental caries as a disorder of mitochondrial dysfunction and metabolic dysregulation represents an important shift in the paradigm of dental caries aetiology with implications for the prevention of dental caries and accompanying poor metabolic health. Current clinical approaches to dental caries predominantly centre on the treatment of caries lesions, often failing to incorporate dietary determinants or to recognise the associations between caries prevalence and other chronic conditions.

Non-dietary prevention of dental caries

The conceptual framework attributing dental caries to the accumulation of calcified plaque, and its presumed eradication through oral hygiene practices, has long underpinned preventive strategies in dental health.¹⁴ Presently, first-line prevention approaches are increasingly reliant on the commercial oral care industry, which encompasses oral hygiene devices, chemical rinses, fluoride-based delivery systems, and antimicrobial agents and was collectively valued at approximately $53 billion as of 2024.¹⁵

Non-dietary oral health promotion strategies include teaching effective oral hygiene practices to target bacteria in the mouth for suppression or elimination by using toothpastes, mouthwashes and other techniques to remove ‘plaque’ from the surfaces of teeth. Other features of oral health promotion include facilitating early access to preventive dental services and directives to add fluoride to the water supply. Investigations into non-dietary interventions for caries prevention have shown considerable heterogeneity in methodological rigour, which has limited the strength and generalisability of their findings.¹⁶ The fundamental limitation with the promotion of these strategies is the failure to address persistent dietary patterns characterised by high-frequency consumption of refined carbohydrates.¹⁷ When dietary regimes with elevated proportions of fermentable carbohydrates were endorsed as preventative for chronic systemic diseases and embedded within government-approved dietary guidelines, dental practitioners were obliged to promote foods previously linked to greater caries burdens.¹⁷ Within the field of preventive dentistry, there was a growing emphasis on non-dietary caries prevention, influenced in part by the dominance of the lipid hypothesis focused on a central principle to restrict saturated fat intake.¹⁷ The idea that carbohydrate restriction could prevent dental disease became increasingly downgraded.¹⁷ In addition, the increasing prominence of the germ theory-based idea that caries would not be present in a ‘clean mouth’ was also enthusiastically endorsed by commercial interests, including the sugar and oral hygiene industries.¹⁴

Dietary prevention

Dental caries may be preventable through adherence to dietary patterns characterised by reduced intake frequency of refined carbohydrates and increased consumption of nutrient-dense foods.¹⁸ However, the benefits of vitamin- and mineral-rich foods for caries prevention were sidelined with the introduction of dietary guidelines that advocated reductions in fat consumption.¹⁸ The implacability of the dominant and ongoing assumption that fat reduction was associated with health benefits has in part led to a paucity of investigations of dietary interventions with a twin focus on the intake of nutrient-rich foods and reduced carbohydrate consumption for caries prevention. Studies of dietary interventions for caries prevention are typically based on adherence to advice provided in dietary guidelines.¹⁷ Dietary recommendations within dental public health initiatives commonly advocate for the reduction of sugar-sweetened foods and beverages and adherence to conventional nutritional guidelines. There is advice to increase both the quantity and frequency of carbohydrate-based food consumption during childhood and to preferentially select low-fat dairy and meat produce.¹⁷ Such guidance is contradictory to empirical evidence regarding the dietary contributors to dental caries and the benefits associated with consumption of full-fat dairy for dental health¹⁹ and the mitigation of metabolic syndrome risk.²⁰

Thus, strategies for caries prevention should target the primary dietary aetiological factor associated with caries, namely, the high and, most critically, frequent intake of refined carbohydrates. Hence, feasible interventions for dental caries prevention may be based on restriction of refined carbohydrates and a focus on the consumption of a nutrient-replete dietary pattern with a focus on vitamin- and mineral-rich foods of a whole and lesser processed nature. Human intervention trials have shown that such strategies effectively mitigate metabolic syndrome, are acceptable, and can confer benefits maintained over several years.²¹

Discussion and conclusion

Contemporary preventive initiatives focused on oral hygiene promotion have demonstrated limited efficacy in achieving enduring improvements in oral health. In addition, current approaches do not consider the diet-induced role of systemic cellular dysfunction in dental caries and other metabolic disorders. The integration of metabolic strategies for the prevention and treatment of dental caries should become a global priority for healthcare systems because of the high prevalence of this condition. Such integration will also require government agencies and professional organisations to construct nutrition policies that reflect the evidence regarding the harmful effects of dietary patterns associated with poor metabolic health.

There is growing acceptance that chronic NCDs are underpinned by a modern dietary lifestyle of a high frequency consumption of refined carbohydrates. Dental caries, the most common diet-related disease worldwide, are typically regarded as a local phenomenon occurring solely because of fermentation of carbohydrates by bacteria in the mouth. Similar to other chronic diet-related diseases, dental caries is characterised by hormonal and metabolic responses designed to lessen cellular exposure to oxidative stress. As such, dental caries should be regarded as a metabolic disorder akin to metabolic syndrome, atherosclerosis, cancer and neurodegenerative disease. Despite this, public health preventive approaches are primarily focused on non-dietary, oral hygiene-based strategies.

The appearance of dental caries in childhood should be regarded as the earliest indicator in the life course of metabolic disease and provide impetus for dietary change interventions for those with this condition. A considerable body of evidence has shown benefits of carbohydrate-restricted dietary patterns in achieving beneficial changes in metabolic syndrome and commonly associated disorders. Prevention of dental caries via dietary patterns characterised by restriction of refined carbohydrates may be efficacious in reducing disease burdens and preventing ongoing metabolic dysfunction through the life course.

The systemic impacts of a dietary pattern characterised by both the restriction of refined carbohydrates in refined carbohydrate-based foods and high intake of vitamin- and mineral-rich foods should be investigated in methodologically rigorous prospective studies to determine the effect of systemic mechanisms on caries aetiology, prevention and treatment. This research should be a priority because of the high prevalence of dental caries through the life course and the lack of efficacy of current preventive and treatment strategies in mitigating the global disease burden of dental caries.

Acknowledgements

This article includes content that overlaps with research originally conducted as part of Sarah Hancock’s doctoral thesis titled ‘Healthy Mouth, Healthy Body: Towards Integrated Dietary Approaches’, submitted to the Faculty of Health and Environmental Sciences, Auckland University of Technology in 2021. The thesis was supervised by Caryn Zinn, Grant Schofield and Simon Thornley. Portions of the data, analysis and/or discussion have been revised, updated and adapted for journal publication. The original thesis is publicly available at: https://openrepository.aut.ac.nz/items/d0ff9db8-de18-404b-bc5c-6c7f5f4b3a73. The authors affirm that this submission complies with ethical standards for secondary publication, and appropriate acknowledgement has been made to the original work.

The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

S.H. and C.H. conceptualised a perspective paper based on the body of evidence and contributed resources to the original manuscript and subsequent drafts. Both authors independently read and evaluated the existing literature.

This article followed all ethical standards for research without direct contact with human or animal subjects.

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Data sharing is not applicable to this article, as there were no new data created or analysed in this study.

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors or that of the publisher. The authors are responsible for this article’s results, findings and content.

References