We used two electronic databases (PubMed and Web of Science) as our tools to search the potential literatures. The literature search through databases was performed on 6 April 2022 until 14 April 2022. We constructed the keywords for each database. For PubMed, we used the following keywords; ((((((coffee [MeSH]) OR (caffeine [MeSH])) OR (“coffee intake”)) OR (“coffee consumption”)) OR (“caffeine intake”)) OR (“caffeine consumption”)) AND ((((mouth [MeSH]) OR (tooth [MeSH])) OR (((“oral health” [MeSH]) OR (“periodontal health”)) OR (“periodontal index” [MeSH]))) OR (((“tooth loss”[MeSH]) OR (periodontitis [MeSH])) OR (periodontal disease [MeSH]))). Meanwhile for Web of Science, the keywords were (((((ALL=(coffee)) OR ALL=(“coffee intake”)) OR ALL=(“coffee consumption”)) OR ALL=(“caffeine intake”)) OR ALL=(“caffeine consumption”)) OR ALL=(caffeine) AND (((((((ALL=(mouth)) OR ALL=(tooth)) OR ALL=(“oral health”)) OR ALL=(“periodontal index”)) OR ALL=(“periodontal health”)) OR ALL=(“periodontal disease”)) OR ALL=(periodontitis)) OR ALL=(“tooth loss”). During the literature search, no time limit was set.

All types of experimental and observational studies in English language were included. No duplicate studies and no treatment or clinical trial studies included. Study subjects include adults without any gender and age restrictions, and any other objects of in vivo and in vitro studies. Study factor or exposure included in the studies were coffee or caffeine intake in a daily basis, any other interventions using caffeine or coffee. Outcome of studies included were oral health status, periodontal health status, periodontal diseases, tooth loss and any other assessment of periodontal conditions.

The aforementioned keywords gave a total number of 895 articles, consisting of 243 and 652 articles from PubMed and Web of Science respectively. We excluded one literature as it was a book chapter. After excluding duplicates and languages, we had 829 potential articles to be reviewed. After conducting title and abstract reading, we had remaining 47 studies. Two researchers reviewed the full text of those studies and finally selected ten of them which met the inclusion criteria. Critical appraisal had been done by two reviewers separately using JBI Critical Appraisal tools. The flow diagram of the selection of study is shown in Figure 1.

The included studies in this review were originally from Asia, America, Europe, and Africa. Out of ten studies, three were from Korea, two were from Japan, another two were from America, and the remaining three were from each of Brazil, Germany, and Egypt. The year of publication ranged from 1999 to 2022. Half of the included studies used cross-sectional study design, three studies were randomized controlled trial, one study used cohort study design, and another one used quasi-experimental study design. This review including studies with various subject, six studies observing the effect of coffee intake on human, ^{8 – 13} three studies exploring the cellular changes using rats as the subject, ^{14 – 16} and one in vitro study observing the coffee effect using UMR106-01 rat osteoblast-like cells. ¹⁷ The summary of the included study were tabulated based on the results, whether coffee intake have positive ( Table 1) or negative effect ( Table 2) on periodontal health.

Human studies

Among six studies, two studies used data from national survey, and choosing the eligible participants based on some criteria. One study used data from dental longitudinal studies, one study used data from Genome and Epidemiology Study, one used general population, and one other study selected chronic periodontitis patients who had received initial treatment as the participants of the study. All of the human studies used questionnaire to assess the dose of daily coffee consumption (all six studies), ^{8 – 13} one study also used Cornell Medical Index (CMI) to gain coffee consumption in addition to questionnaire. ⁹ Two studies admitted that validity and reliability test of the questionnaire were not performed sufficiently, therefore, further research is required. ^{11 , 12}

The assessment of periodontal health was mostly performed using various reliable ways, however, one study only ask whether the participants ever diagnosed with periodontitis without further clinical examination. ¹¹ The clinical oral examination performed to assess periodontal health including scoring method according to American Association of Periodontology by probing pocket depth and clinical attachment level, ¹² using Community Periodontal Index (CPI), ^{8 , 10} radiographic examination to measure alveolar bone loss, measurement of probing depth, ^{9 , 13} bleeding on probing, ^{9 , 13} gingival recession, ¹³ and examining supragingival calculus, ^{9 , 13} and plaque index score. ¹³ Aside from periodontal health, caries measurement using DMFT index was also performed. ¹³

In terms of bias, some studies also observed several confounding factors, such as Body Mass Index (BMI) ^{9 , 11 , 13} and other nutritional intake, ¹¹ smoking and alcohol habit, ^{9 , 11 – 13} medical history such as diabetes, ^{8 , 9 , 12 , 13} cholesterol level ⁸ and coronary heart diseases, ^{12 , 13} blood sample analysis, ⁸ and other socio-demographic factors. ^{10 , 12}

Animal studies

The animal studies were performed with various designs. One study induced periodontitis on rats by means of ligature placement, then made comparisons between groups with and without caffeine ingestion (Bezerra et al). The two other studies observed the effect of giving green coffee bean extract (Abbas) and powdered coffee (Kobayashi) on periodontal health of the rats. Histological examinations were performed to assess the effect, by observing bone structure and volume (Abbas, bezerra, kobayashi), RANKL expression (bezerra), measuring serum oxidative stress and antioxidant capacity, 8-OHdG and Nrf2 positive cells, and gene expression analysis (Kobayashi).

In vitro study

The only one in vitro study was observing any possible interaction between Prostaglandin E2 (PGE2) and caffeine using UMR106-01 rat osteoblast-like cells.

The favorable effects of coffee intake on periodontal health

The minority of the included studies managed to reveal the benefits of coffee intake on periodontal health. Studies found that coffee intake might be beneficial against periodontal disease. ^{9 , 10} Another study on patient with periodontitis during maintenance phase of therapy also showed those who drank more than one cup of coffee in a day had lower prevalence of severe periodontitis. However, no such significant difference found on the prevalence of moderate periodontitis. ¹² An in vivo study using revealed that consuming coffee had a protective effect against periodontal diseases. The result showed a lower ratio of 8-OHdG-positive cells in the group with the highest dose of coffee intake, compared to those in the control and other treatment group with lower dose of coffee. The study also identified that coffee intake improve the antioxidant activity in periodontal tissue by upregulating Nrf2 signaling pathway. ¹⁶ However, Hong et al (2021) revealed that there is no significant association between coffee intakes and periodontitis as the adjusted ratio were not statistically significant. ¹¹

The drawbacks of coffee consumption on periodontal health

Five studies found out that consuming coffee might also have negative impacts on periodontal tissue, especially the alveolar bone. An animal study comparing the effect of consuming two different dietary supplement (green coffee extract/GC and Agiolax ^®/Ag) on alveolar bone loss. Both supplements showing deleterious effect towards periodontal health, however, GC groups showed greater alveolar bone loss compared to Ag groups. ¹⁴ Another study on periodontitis-induced rats by placing a cotton ligature also showing that caffeine ingestion causing larger area of bone loss, even though without ligature placement, caffeine alone was unable to induce alveolar bone loss. ¹⁵ The only in-vitro study in this review investigated the interaction between caffeine and prostaglandin E2 (PGE2) on rats’ osteoblast-like cells. It showed significant inhibition of cell proliferation when both caffeine and PGE2 were incubated together and the inhibition were stronger as the dose higher. ¹⁷ Lastly, two human studies also indicated the destructive effect of coffee on periodontal tissue. ^{8 , 13}

Interestingly, the current review covers several study designs and settings, taking humans, animals, and culture medium as their objects of study. However, some studies did not state the possible confounding factors and ways to deal with it. ^{8 – 10}

Periodontitis is an inflammatory disease that mainly caused by microorganisms that present as the destruction of teeth supporting tissue. Periodontitis is also associated with the presence of reactive oxygen species (ROS) as a result of hyperactivity of peripheral blood neutrophils. Its hyperactivity may occur as a reaction of host-immune reaction to the inflammation of periodontitis. Not only neutrophils, the infection of bacteria producing ROS might also be contributed to the oxidative stress in periodontitis, leading to the progression of alveolar bone loss.

Coffee is considered as one of the most antioxidant-rich beverages as it has various components that were found to have antioxidant and anti-inflammatory properties; caffeine, chlorogenic acid, and caffeic acid. Due to the presence of such effects, there might be protective impacts of coffee in periodontal diseases. ^{8 , 10} A study suggest that phenolic content in coffee have strong antioxidant properties, thus might reduce oxidative stress due to bacterial activity. In addition, the recent replacement of cream with skimmed milk powder in the coffee mix is thought to be helpful in preventing osteoporosis, thus can also be protective against periodontal bone loss. ^{10 , 18} Milk belongs to dairy products, with calcium and casein content that is helpful in bone and tooth mineral preservation. ¹⁸ Other explanation of the coffee protective effect against alveolar bone loss is also presented by Ng et al. It was stated that caffeine has immunomodulatory actions by inhibiting cyclic adenosine monophosphatase (cAMP)-phospodiesterase, thus increasing the concentration of intracellular cAMP. ⁹ Another supporting result was also presented by Machida et al that observed the effect of consuming coffee during the maintenance phase of periodontal therapy. ¹² Besides, chlorogenic acid contents in coffee also known to act as antimicrobial agent by reducing the protease activity of Porphyromonas gingivalis. Those are bacteria that commonly found in plaque biofilm that plays role in the periodontal disease progression. ^{11 , 19}

A cellular molecular observation also found that chlorogenic acid contained in coffee can significantly decrease malondialdehyde, which is the result of lipid peroxidation degradation, and increase catalase, superoxide dismutase, and glutathione. Thus, reducing oxidative stress. However, the study was focus on the anti-aging effect of coffee intake toward oxidative stress on periodontal tissues, without considering the normal flora. Thus, the effect on periodontal disease might be slightly different. ¹⁶

The similar findings have been shown through gene expression analysis. Some genes that were having a role in the antioxidant effect were highly expressed in the highest percentage of coffee group; glutamate cysteine ligase modifier subunit, ferritin, and hypoxanthine phosphoribosyltransferase 1 genes. ²⁰ Glutamate cysteine ligase (modifier subunit) has a role to maintain the synthesis of glutathione, one of the largest intracellular antioxidants. Meanwhile, ferritin has a protective role against iron-dependent oxidative stress. The cellular defense against oxidative stress may occur through the activation of Nrf2 signaling pathways which controls the genes that involved in the elimination of reactive oxidants by increasing the cellular antioxidant capacity. ²¹ This notion is consistent with the study result showing the more frequent of Nrf2 nuclear translocation in the highest percentage of coffee group. ²⁰ It is indicated that the continuous intake of coffee lead to some increase in the antioxidant capacity of the periodontal tissue, decreasing age-related oxidative stress in the tissues. The systemic increase of antioxidant activities may contribute to a decrease in oxidative damage at the local level. ²² Hence, the systemic approaches including dietary habits may also provide promising benefits in the treatment of periodontal diseases. ¹²

In contrast, many studies reported the detrimental effects of coffee intake on periodontal disease. ^{8 , 13 – 15 , 17} Hypotheses explaining the association might focus on the caffeine as the major content in coffee. ^{8 , 14} Caffeine is reported to affect calcium metabolism and evoking bone mineral density. Thus, long-term caffeine intake denotes one of the risk factors in the advancement of periodontitis pathology. Another study revealed that caffeine may increase bone loss and alter bone healing following tooth extraction. ⁸ There are several pharmacological and cellular activities of caffeine on bone metabolism related to osteoblast proliferation and calcium metabolism. ^{8 , 14 , 15} Caffeine is known to be able to inhibit the osteoblast-like cells proliferation, also have negative impacts towards the viability of osteoblast, leading to the increase of apoptosis rate of the cells. ¹⁵ The negative impacts towards these cells are due to the caffeine ability to disrupt the mitochondria of osteoblast and osteocyte in vivo. ¹⁷ Caffeine can also increase the expression of the receptor activator of NF-κB ligand (RANKL), as the result of low calcium levels in blood. The low level of calcium will be responded by the increase secretion of parathyroid hormone, and stimulate the osteoclast to increase calcium blood levels through expressing RANKL. ¹⁴ Alveolar bone loss in periodontitis is mediated by tumor necrosis factor (TNF)-α, interleukin (IL)-6, RANKL, and prostaglandin E2 (PGE2) as the response to a pathogens. A combination of PGE2 and caffeine in blood strongly inhibit osteoblast proliferation. ^{15 , 17} This might be the reason behind the absence of coffee consumption effect toward healthy periodontal tissue. The contradictory effects of coffee consumption might be caused by several factors. First of all, the roast degree can alter the amount of chlorogenic acid content in the coffee, thus might also affect its anti-oxidant, anti-bacterial and anti-inflammatory activity. ¹⁹ Secondly, the caffeine content in each coffee consumed may vary, and the last possible causes is the additives content in coffee (milk, sugar, cream) consumed might also contribute to different effects of coffee. ²³ In addition, the effects of coffee on health work in a dose-dependent manner. The high dose of caffeine administered daily in an in vivo study that causes bone destruction was equivalent to 1,360mg/70kg ^0.75 in humans. ¹⁵ This dosage was equivalent to 16 cups of coffee per day. Meanwhile, the suggested daily intake of coffee that is considered to be safe is around four-five cups per day.

As we did limit the language to be English only, many studies written in non-English were not covered in this review which may lead to language bias. The various designs used in the selected studies gave a wide range of results and it is not feasible to quantitatively summarize the selected studies. Besides, the measurement of periodontal health as the study outcome is various, giving a challenge to meaningfully compare among one and another. Moreover, the majority of studies were a cross-sectional study which cannot answer the causality of the findings. In future studies, it will be necessary to observe the potential antioxidant effects on periodontal tissue by measuring the antioxidant marker on gingival crevicular fluid (GCF) sample.