Dental and oral implications of prescribed Oral Nutritional Supplements for disease related malnutrition- A systematic review

1.1Oral Nutritional Supplements

Oral Nutritional Supplements (ONS) or Food for Special Medical Purposes (FMSP) are a form of oral nutrition therapy, “developed to provide energy and nutrient-dense solutions that are provided as ready to drink liquids, cremes or powder supplements that can be prepared as drinks or added to drinks and foods” [1]. They can be provided in the management of patients with a “limited, impaired or disturbed capacity to take, digest, absorb, metabolise or excrete ordinary food or certain nutrients contained therein, or metabolites, or with other medically-determined nutrient requirements, whose dietary management cannot be achieved by modification of the normal diet alone” [1, 2].

Reasons for prescribing ONS are listed in Table 1 below [3]

It can be seen from Table 1 that there are some circumstances where the consumption of ONS will only be short term, e.g. post-operatively after a gastrectomy, however individuals with chronic conditions such as cystic fibrosis or renal disease. Therefore, any effects ONS may have on the oral environment will most likely be dependent on amount, type and duration of ONS that would be prescribed and consumed.

A recent study in Ireland found that the majority of people taking ONS were female (58.2%), the median age was 76 years and 18.7% were in residential care [11]. This is similar to global studies, with the majority (72.5%) of ONS consumers being female, with a mean age of 81.9 years and ONS being prescribed to 13.9% of nursing home residents [12, 13]. This varies from country to country, with only 1.2% of nursing home residents receiving ONS in Portugal, compared to 43.2% in Turkey [12]. Another study, from the Republic of Ireland found that the majority of patients they examined were prescribed ONS for more than 6 months without review [3].

The benefits of ONS for malnourished individuals are well-established [14, 15] and include reduced mortality, reduction in number of hospital admissions and duration of hospital stays in people who are malnourished [16]. Recent studies have shown protein-rich ONS as a promising treatment for sarcopenia [17]. They have also been shown to improve patients’ quality of life and can result in a gain in quality-adjusted life years (QALYs) [18]. Despite these clear benefits, there have been some adverse effects reported, such as nausea and diarrhoea [14], and concerns have been raised about the cost-effectiveness of ONS [19]. Also of note is the sugar content in ONS, which can be significant. A recent study showed that some of the most common ONS on the market can contain up to 35 g of sugar per 200 ml whole milk reconstitution [20].

1.2Oral disease

Oral disease includes all diseases of the mouth, both hard tissues (teeth) and soft tissues (mucosa including gingivae). The Global Burden of Disease Study 2017 found that oral diseases were the most common diseases found in mankind, affecting close to 3.5 billion people worldwide [21]. The most common of these was dental caries (“tooth decay”) which affects approximately 2.3 billion people with permanent teeth and the deciduous teeth of 530 million children. Other common oral diseases include periodontal (“gum disease”) and oral candidiasis (“thrush”). It is recognised that oral diseases can impact upon people’s quality of life and well-being, tools such as the Oral Health Impact Profile (OHIP) [22, 23]. Untreated dental disease can result in pain, discomfort and affect an individual’s physical functions such as chewing, smiling and talking and impact upon the individual’s social roles [24]. Elderly people with dental disease are at increased risk of oral frailty, which can be defined as decline in oral function which impacts an individual’s ability to chew, speak and swallow [25]. This in turn can lead to an increased risk of frailty, sarcopenia, disability, and mortality [25].

Dental caries is the localised destruction of dental hard tissues (enamel and dentine) by acidic by-products from the bacterial fermentation of free sugars [26]. This is presented in a simplified visual format in Fig. 1. These sugars can come in the form of added monosaccharides (e.g. glucose (dextrose) and fructose) and disaccharides (e.g. sucrose, lactose and maltose) or sugars naturally present in honey, syrups, fruit juices and fruit juice concentrates [27]. Intake of dietary sugars is the most important risk factor for dental caries, and both the frequency and the amount of sugars consumed are important in caries development [28]. In relation to ONS, many are described as “sip-feeds” in that they should be “sipped” on frequently throughout the day, which will result in increased exposure to any sugars contained. In Ireland, very high-energy sip feeds are the most frequently dispensed type (45% of the cohort examined) [11].

If carious lesions progress, they can lead to cavitation resulting in pain and discomfort. If left untreated, caries can eventually result in infection, sepsis and tooth loss. Exposure to fluoride can limit disease progression as fluoride promotes remineralisation of the dental hard tissues [26]. There is a high prevalence of dental caries amongst old-age populations, with the 2009 UK Adult Dental Health Survey reporting that 27% of adults aged 65–74 years had evidence of dental caries, and this figure increased to 40% for those aged 75–84 years [29, 30].

Fig. 1

A simplified visual representation of the multifactorial aetiology of dental caries. Dietary sugars are metabolized by bacteria present in dental biofilms, generating acidic by-products that can lead to caries. The fourth factor that this disease process depends on is time, i.e. that it will take time for this process to occur.

Fig. 2

Patient with periodontal disease. Note erythema around gingival margin, loss of interdental papillae, recession and tooth loss associated with this disease (Photo credit: Prof. Anthony Roberts, UCC).

Periodontal diseases (namely, gingivitis and periodontitis) are chronic inflammatory conditions of the tissues surrounding the teeth [26]. Gingivitis, which may be seen clinically as red, swollen gums which bleed on probing, is considered to be reversible when adequate oral hygiene measures are implemented and maintained [31]. Periodontitis involves the destruction of the supporting structures of the teeth, which includes the periodontal ligament, bone and soft tissues. Although gingivitis must precede periodontitis, not all cases of gingivitis progress to periodontitis and it can be said to have a site and subject predilection [32]. Similar to dental caries, the prevalence of periodontitis increases with age, and it is a major cause of tooth loss in older adults [33]. Other risk factors for periodontal disease include being of the male gender and genetic conditions, such as Down syndrome [34–36]. Smoking has also been proven to lead to an increase in periodontal disease rates and a decrease in success rates following periodontal treatment [37, 38]. Sugar has also been suggested as a risk factor: analysis of 2437 young adults found that “A high frequency of consumption of added sugars is associated with periodontal disease, independent of traditional risk factors, suggesting that this consumption pattern may contribute to the systemic inflammation observed in periodontal disease” [39].

The European Federation of Periodontology discussed in a 2016 workshop that dental caries and periodontal disease share common genetic, aetiological and environmental factors, and that the prevention and treatment of both disease entities can share similar pathways [40, 41].

Oral candidiasis, commonly known as ‘thrush”, is an opportunistic fungal infection of the oral cavity. The main causative agent, Candida albicans, is a commensal organism, generally regarded as a normal and harmless member of the oral microbiome in humans. However, changes in the host microenvironment can cause it to become pathogenic [42–44]. A key virulence attribute of Candida is its ability to adhere to the host surface, be that the oral epithelium or surfaces of intra-oral prosthetic devices e.g. dentures, orthodontic appliances [44]. Local risk factors for oral candidiasis include salivary dysfunction, poor denture hygiene and ill-fitting dentures, and topical corticosteroid treatment [42]. Systemic factors include broad spectrum antibiotics, immunosuppressive therapy and intake of dietary carbohydrates [42, 45, 46].

Therefore, it can be seen that high sugar consumption is cited as a risk factor in these three common oral diseases. Due the high sugar content of many ONS, and due to the fact that they are often prescribed as “sip feeds” to be taken throughout the day, a systematic review was carried out to investigate if there are any studies examining if ONS result in a higher prevalence of dental disease.

2.1Protocol

This study was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines adapted by Liberati [47]. The PICO question was as follows:

Population: Individuals (both children and adults)

Intervention: Use of Oral Nutritional Supplements

Comparison: Individuals not taking Oral Nutritional Supplements

Outcome: Increased risk of oral disease (specifically dental caries, periodontal disease or candida)

The research question was: “Are people who take ONS at higher risk of oral diseases than the general population?”

The primary aim of this review was to establish if the use of ONS leads to an increase in oral disease levels.

The secondary aim was to search for any studies on the effect of ONS on oral hard and soft tissues, or on oral microbiota.

Eligibility criteria

The results obtained from the literature search were filtered, according to these inclusion and exclusion criteria:

Inclusion criteria

Exclusion criteria

2.2Information sources

The searches were conducted in the following electronic databases: Medline (via Ebsco), Embase, Web of Science Core Collection, Google Scholar. These databases were selected due to recommendations for optimal searches in systematic reviews [48]. The bibliographies of relevant articles were hand- searched to identify any additional studies that may have not been captured by the digital searches.

2.3Search strategy and selection criteria

The following search terms were used ““Dental health” “periodont*” “caries” “dental” “candida” AND “oral nutritional supplements”. An example of a search strategy in included in appendix 1. The search was last run on 14/11/2021. Two investigators (N.C., F.O’L.) independently reviewed titles and abstracts to determine eligibility for inclusion. Full articles were obtained for the identified titles and those which met the selection criteria were included. Differences of opinion of the two investigators about study eligibility were resolved by discussion with a third author (M.H.).

2.4Risk of bias

For each of the studies, a risk of bias assessment was performed using the ROBINS-I tool for assessing risk of bias in non-randomised studies [49]. Different items are evaluated as described in the ROBINS-I checklist. The items include questions asking for adequate randomization, allocation to appropriate comparison groups and the accounting for confounding and modifying variables, among others. Each item is rated with as Low, Moderate, Serious or Critical risk of bias, or that “no information” was given on which to base a judgement about risk of bias.

3.1Study characteristics

Two of the studies [51, 52] were in vitro studies and the third study was an in vivo study [53]. The first study [51] examined the cariogenicity of a milk-based dietary supplement that is distributed to older adults in Chile. The second study [52] investigated if oral microorganisms can proliferate in thickened drinks including ONS. (The second aspect of this study examined lemon-flavoured thickened drinks, but as these did not fit into the inclusion criteria, this is not included in the qualitative review). The third study [53] measured cariogenic potential in vivo utilising intraoral plaque telemetry. As the studies are heterogenous in nature, a meta-analysis was not possible and they will be discussed separately.

3.2Study results

Study No.1: Castro et al, 2019

The aim of this study was “to evaluate the cariogenicity of a milk-based drink intended for older adults that was used as part of a governmental initiative in Chile to improve their nutritional conditions”. The study used a previously validated experimental caries model with bio-films of Streptococcus mutans. 4 items were tested:

The composition of the milk-based drink (Appendix 2) is comparable to other Oral Nutritional supplements [40] and is included in Appendix 2.

The method involved the use of bovine dentine (the main hard dental tissue found on root surfaces) slabs, combined with salivary pellicle from healthy volunteers, inoculated with streptococcus mutans (the main cariogenic bacteria). After 24 hours of biofilm growth, dentine slabs were exposed to the different treatments 3 times per day (at 8 : 30 am, 12 : 30 pm, and 4 : 30 pm) for 5 min. After each treatment, biofilms were washed three times in 0.9% NaCl, and relocated to a medium containing well. Culture medium was changed twice per day before the first (at 8 am) and after the last treatment. The samples were tested for biofilm acidogenicity, dentine demineralisation and viable microorganisms present. The results showed that the milk-based drink had higher cariogenic potential than milk (higher acidogenicity). However, there was no statistical difference in dentine demineralisation and no significant difference in viable micro-organisms present.

This study concluded that the tested milk-based drink used as a dietary supplement for older adults in Chile shows a potential risk for root caries, higher than whole milk. The authors also stressed the importance of testing the cariogenic potential of the dietary supplements available to the elderly population.

Study No.2: Jung et al. 2019

The aim of this study was to investigate in vitro microbial survival or proliferation in ONS. In this study, 4 drinks were tested:

Seven samples of part open ONS were collected from the Geriatric Ward of Nice University Hospital to verify if they were contaminated after opening and consumption. They had been open for less than 2 hours. They were collected by nurse aides, transported at 4°to the laboratory and immediately inoculated onto Petri dishes. 100μL of ONS were diluted in 900μL of saline water and this 1-mL inoclulum was plated onto sheep blood agar plates. Plates were incubated for 5 days in microaerophilic conditions, adapted to oral microflora, to replicate the oral environment in vivo.

Results were expressed as a qualitative evaluation of the rate of ONS contamination, ranging from – to+++, based on Colony Forming Units (CFUs) numeration on Petri dishes. The samples were tested for 3 micro-organisms: Escherichia coli, Staphylococcus aureus and C. albicans. Qualitative evaluation of microbial growth in the different ONS showed that E. coli, S aureus and C. albicans all grew at room temperature (20° C) in dairy drinks and creams. C. albicans also grew in the juice which was milk protein-free and lipid-free.

The study concluded that ONS are similar to some bacterial and fungal culture media, and may pose a risk of iatrogenic infection for people who consume these.

The degree of contamination was not bound to the type of ONS (dairy ONS vs. juice) but to the contamination of the product by the oral flora of the patient-both types contributed to preserving the viability of some microaerophilic oral strains.

The authors also concluded that ONS could be a source of contamination to other body sites and could increase the risk of aspiration pneumonia.

Study No.3: Stillhart et al., 2021

The aim of this study was to evaluate the cariogenic potential of ONS using intraoral plaque telemetry.

Ten ONS were tested on five healthy volunteers (having no active caries and no medications). A test electrode in a partial denture recorded the plaque-pH values measured for 30minutes. Participants were requested to refrain from toothbrushing and oral hygiene measures for at least 3–7 days in order to allow dental biofilm to build up. The oral fluid was neutralised by chewing on paraffin wax. The participants were then given the ONS and held the solution in the mouth for 2 minutes. pH measurements were recorded for 30 minutes. A rinse with water was then carries out, and participants chewed on paraffin again to neutralise the pH and the saliva. A control solution of 10% sugar was then administered under the same conditions as the ONS. Relative cariogenicity (RC) was expressed as a mean+/– standard deviation. The AuCp (area under the curve) ranged between 6.02±4.34 and 30.57±14.03.

This study showed that all the tested ONS were potentially cariogenic on enamel.

3.3Risk of bias assessment

Different items are evaluated as described in the ROBINS-I checklist for assessing risk of bias in non-randomized studies of interventions. The items include questions asking about adequate randomization, allocation to appropriate comparison groups and the accounting for confounding and modifying variables, among others. Each item is rated with as Low, Moderate, Serious or Critical risk of bias, or that “no information” was given on which to base a judgement about risk of bias. Two of the studies [51, 53] were classified as being at low risk of bias, based on the domains described in the ROBINS-I tool. The study by Jung et al. was classified as being at serious risk of bias. The checklist is presented in Table 2.

Table 2

Risk of Bias assessment