Content of potentially toxic elements (PTEs) in coffee and coffee-based products: a meta-analysis study, Systematic review, and health risk assessment

Abstract Coffee is the most popular beverage after water in the world, which has an important role in health as a result of various minerals and vitamins but it may be pollution source of potentially toxic elements (PTEs) that can threate the health. Thus, the current study intended to detect the level of PTEs such as Cadmium (Cd), Copper (Cu), Lead (Pb), Nickel (Ni), Znc (Zn) and Iron (Fe), in various coffee and coffee-based products (powder, ground, processed, infusion and bean). Considering the databases of Scopus, Google scholar, PubMed, and Web of Science, the concentration of PTEs in coffee and coffee-based products was retrieved and meta-analyzed. Additionally, the non-carcinogenic risks in terms of total hazard quotient (TTHQ) were assessed using Monte Carlo simulated (MCS) model. According to the findings of 23 articles, the ranking of metal concentration in different coffees was Fe > Zn > Cu> Ni > Pb > Cd in powder, Fe > Cu > Zn> Ni in ground, Fe > Zn > Ni> Cu> Pb > Cd in processed and infusion and Fe > Zn > Ni> Cs > Pb in bean. Moreover, based on WHO regions, the highest concentrations of Cd and Pb (0.742 mg/kg) were related to the South-East Asia Region (SEARO) and European region (EURO) respectively. However, the highest concentrations of Fe (81.161 mg/kg), Zn (33.392 mg/kg), Cu (9.408 mg/kg), and Ni (18.064 mg/kg) were related to Pan American health organization (PAHO), PAHO, PAHO and Eastern Mediterranean Region (EMRO), respectively. On the other hand, the risk pattern was different in different countries. Moreover, consumers in some countries were not at significant non-carcinogenic risks because of ingestion of PTEs via coffee and consumption of coffee-based products.


Introduction
There are concerns regarding the contamination of different food products such as vegetable oil, cereal, and fruit and dairy with metals for both industry and academic (Heshmati et al. 2020, Ghane et al. 2021, Khazaei et al. 2021, Rahimi et al. 2021).Coffee is frequently used by consumers because of its sensory characteristics such as aroma, taste, and created alertness.It is made from the beans family tree.There are various species of coffee (Trindade et al. 2020).Coffee contains a variety of nutrients such as protein, lipids, carbohydrates, chlorogenic acids, tannin, polyphenols, and various minerals and vitamins (Debastiani et al. 2019).Drinking coffee can regularly upgrade the glutathione level while protecting the body against DNA injury (Winiarska-Mieczan et al. 2021).Coffee is made from soluble instant powder or groundroasted coffee beans with a very complex matrix.After water, it is the most popular nonalcoholic beverage in the world (Voica et al. 2016).Indeed, there is an annual profit of about 60 billion dollars in the coffee industry compared to inedible oil (petroleum) in this respect (Al-Dalain et al. 2020).As mentioned by the International Coffee Organization, the annual production of coffee in the world in 2020 was estimated at 169.5 million bags (ICO , 2021).Several studies have been carried out on the health effects of coffee, indicating its beneficial effect on diseases such as Alzheimer's, Parkinson's, type 2 diabetes, while reducing the risk of depression and hypertension (G ongora-Alfaro 2010, Hjellvik et al. 2011, Lucas et al. 2011).Coffee is an important source of trace and essential elements that are daily required, such as copper (Cu), manganese (Mn), magnesium (Mn), Calcium (Ca), iron (Fe), potassium (K), phosphorus (P), and zinc (Zn).However, some elements of heavy metals such as cadmium (Cd), mercury (Hg), nickel (Ni), and lead (Pb) in coffee are harmful to health (Al-Dalain et al. 2020).Therefore, it is important to study the metal concentrations in coffee.Heavy metals remain stable in the environment for a long time and can accumulate in the environment and soil thus leading to the transfer of heavy metals to the food chain and accumulation.This can be a source of contamination and potential threat to human health (Pigozzi et al. 2018, Bounar et al. 2020).Besides, the concentration and composition of different elements can be affected by geographical area, temperature, climate, elevation, soil type and it is chemical composition, field practices, coffee plant species, processing method, fertilizers and pesticides (Habte et al. 2016, Debastiani et al. 2019).In order to confirm the health of fruits for consumers, different guidelines have been set by some countries for assessing the concentration of toxic metals in various food products (Joint FAO/WHO Expert Committee on Food Additives 2010).The toxicity of metals is different based on the type intensity, duration, frequency, and exposure routes to the metals (Ezeonyejiaku and Obiakor 2017).Heavy metals are highly toxic and harmful for humans, for example, they can disrupt ionic mineral balance and create neoplastic transformations thus leading to stimulating oxidative damage to DNA (Kowalska 2021).Exposure to arsenic has adverse effects on organs such as the heart, kidneys, liver, skin, nerve system, gastrointestinal, and respiratory system, leading to developmental anomalies, blood disorders, and cancer.Moreover, exposure to a high concentration of Pb can disturb the kidney, red blood cells, reproductive systems, and the central nervous system while causing memory disorder and delays in response times (Khazaei et al. 2021).Furthermore, Cd can damage the lung and kidney tissue (Heshmati et al. 2020).Long chronic exposure to zinc can result in impairment in disruption of protein metabolism and arteriosclerosis.Brain damage, iron deficiency, and destruction of cells membranes are among the side effect of elevated levels of copper (Parveen et al. 2003).It is reported that exposure to the high level of Ni can also lead to deficiency of Zn or Fe and enzymes malfunctioning (J€ arup 2003).Several reports have been recently presented regarding different metal contamination in coffee (Nogaim et al. 2014, Qin et al. 2015, Stelmach et al. 2015).On the other hand, various studies have been performed on the concentration of heavy metals and essential elements in coffee presenting different results.A metaanalysis study can comprehensively show the distribution of concentrations of different elements in coffee worldwide.To the best of our knowledge, no meta-analysis study has been conducted on this subject, so far.Therefore, the present study aimed to evaluate the concentration and the non-carcinogenic risks of PTEs (Cd, Pb, Cu, Zn, Fe and Ni) in coffee and coffee-based products (powder, ground, processed, infusion and bean) using systematic review and meta-analysis.

Inclusion, exclusion criteria and extraction of data
In this systematic review, according to inclusion and exclusion criteria, all articles were evaluated by two researchers, (FM, and AR), independently based on title and abstract.the difference between manuscripts among the investigators was agreed by reexamining the articles and was subsequently approved by a third author.The studies were included based on the following criteria were including (1) full-text and English language available articles (2) cross-sectional and descriptive study; (3) recording of mean and standard deviation of heavy metals in coffee (Salahinejad and Aflaki 2010, G€ okbel et al. 2015, Gao et al. 2022).In this regard, qualitative studies, duplicates, case reports, clinical trials, review articles, letters to editors, and all studies that evaluated the kind of various processing to remove metals in coffee, and also the fate of metals in coffee and its products were excluded from the study, besides articles that did not mention the name of authors, mean values, raw data, standard deviations, year of publication, country type and brand of coffee were excluded.The following information was included in the dataset such as the year; country; type of coffee; sample size; the average and standard deviation of each study.Aiming to unify units, all units of toxic metals including ppb and ng/g, and lg/kg were changed to mg/kg.

Meta-analysis
The content of metals in coffee and coffee-based products was calculated using mean and standard error.SE was calculated using the mentioned Equation In this equation; N and SD indicate sample size and, standard deviation, respectively.
Weight of study (Wi) was calculated by the following equation (2) The relative weight (RW) was calculated by the following equation In this equation, P W is sum Wi and Wi, the weight of the study (Khaneghah et al. 2020).Analysis method was accepted to assess the pooled concentration of metals in coffee and coffee-based products using a random effect model.Subgroup analysis was independently conducted based on country and type of coffee.A chi-square test was conducted to detect heterogeneity.Heterogeneity of meta-analysis was designed by Q and I 2 tests.Cochran Q test (Q statistic, p < 0.10) and I 2 statistic (I 2 > 50%) showed statistically significant heterogeneity and large heterogeneity respectively.Data were evaluated by the Stata software, version 11 (StataCorp, College Station, TX, USA).P < 0.05 was considered as significant.

Non-carcinogenic risk assessment
The non-carcinogenic risk due to the intake of metals by consumption of coffee was investigated using the current equation C indicates the mean level of metals in various coffees (mg/kg); IR, ingestion rate of coffee is shown in Table 3; ED, exposure interval (adults ¼ 30 years); Body weight (BW) (adults ¼ 70 kg); EF, exposure occurrence (350 days/year); ATn, meantime exposure (adults ¼ 10,950 days).Furthermore, target hazard quotient (THQ) due to the intake toxic metals in different coffees was measured by the following equation (Einolghozati et al. 2022): In this equation, (EDI) and RfD indicate Estimated daily intake and oral reference dose respectively.TDI of Pb and RfD of Cd, Zn, Cu, Fe, and Ni was 0.0036, 0.001, 0.3, 0.04, 0.7, and 0.02 mg/kg/day, respectively (Heshmati et al. 2020).
TTHQ display the amount of THQ for each metal if TTHQ was lower than 1, The health risk is acceptable (Ghane et al. 2022).

Uncertainty analysis using monte carlo simulated (MCS)
Monte Carlo simulated (MCS) technique was recommended by EPAI in order to raise the precise risk assessment via considering uncertainties.To conduct this method, the parameters like the concentration of metals (C), ingestion rate (IR), and body weight (BW) were considered as lognormal distribution using the Oracle Crystal Ball software (version 11.1.2.4.600).The amount of repetitions at 10,000 and percentile 95% of THQ s considered as the cut point of human health risk (Khazaei et al. 2021).

Results and discussion
Retrieve studies process discussion articles that met all required criteria were retained in this study (Figure 1).

Specifications of study
The study characteristics and results have been shown in  1).(Morgano et al. 2002).Copper in various forms including copper oxychloride, copper hydroxide, and copper sulfate is an active ingredient of pesticides used in coffee plant cultivation.This element can be also present in the soil.Thus, the Cu amount is based on its origin (Senkondo et al. 2015).A wide concentration of metals found in various coffees can be related to other factors such as human activities (waste from mining, the cosmetics industry, the steel industry), agricultural activities, origin, and chemical characteristics of raw materials used for coffee production (De Moura et al. 2010, da Silva et al. 2017).

Results of a meta-analysis on metals in coffee based on various continents
The content of metals in the different coffee samples was different among the continents.As shown in  Ozcan (2014), in Saudi Arabia.In these studies, the concentration of different metals studied such as Pb, Cd, Fe, Zn, Cu, and Ni in various samples of coffee including powder, ground, processed, infusion, and bean.According to the findings of these studies, there were significant differences in metal concentrations between different studies.Among factors affecting the metal concentration in coffee between different countries iscontamination with specific metals in the country, the existence of resources and industries, climate conditions and atmospheric pollution, natural sources (volcanic eruptions, weathering of soils and rocks, wildfires), different analytical techniques, storage, transportation and processing and different methods of preparation (Ashu and Chandravanshi 2011).Stelmach et al. and Nogaim et al. investigated Cu, Fe, and Pb metal contents in various coffee beans from Africa, America, Asia, and Yemen, respectively.Reporting different concentrations for Pb metal, they confirmed that coffee beans growing in the mentioned geographical regions are impressed by different chemical compositions (Nogaim et al. 2014, Stelmach et al. 2015).Consistent with these results, Oliveira et al. studied the concentration of metals in infusions prepared from roasted coffee beans from Brazil, India, Mexico, Honduras, Papua New Guinea, Cuba, Timor, and China.They represented different values for Fe metal and observed that the metals profiles of the beverages coffee were related to both inter-and intracontinental differences (Oliveira et al. 2015).Od zakovi c et al. reported that the content of metals in coffee beans is also influenced by industrial processes such as drying, roasting, burning, and storage (Ashu andChandravanshi 2011, Od zakovi c et al. 2017).In another study, the content of metals in infusion is influenced by brewing methods and water used to prepare beverages (Długaszek et al. 2010).In a similar study, it was reported that processing technical and roasting conditions cause the difference in the blends and quality of coffee in terms of the metal concentrations (Ranheim and Halvorsen 2005).As mentioned by various authors, the difference in sampling, preparation and analytical methods have an important role in the metal level in coffee.For example, Stelmach et al., observed that the increased heat of water used for the coffee preparation brews can lead to increase Fe amount in coffee (Stelmach et al. 2013).Other sources of coffee pollution with toxic metals in various continents can be related to the climatic property including humidity, rainy season, and temperature, besides the agricultural technique.Ahmed et al. (2019) concluded that in the wet season of the year, metal fall dilute the irrigation water thus decreasing the level of metals in the soil (Ahmed et al. 2019).In regions where the earth's crust is contaminated with Cd metal, the organic substances of the soil can be absorbed while contaminating human nutrition due to transportation by the food chain (Korish and Attia 2020).

Risk assessment of health
Table 3 represents the non-carcinogenic risk assessment of toxic metals based on consumption of coffee and coffee-based products in different countries.The ranking of countries according to TTHQ in the adult consumers was as Brazil > Poland > Saudi Arabia > England > Ethiopia > Jordan > Philippines > Indian > Pakistan.The results obtained by a risk assessment of metals in different countries indicated different patterns as a result of the difference in coffee and coffee-based products consumption content in various countries, coffee consumption per capita, the concentration of metals in soil and water used for coffee plant cultivation (Getachew and Worku 2014).The findings revealed that TTHQ amounts for consumers in all investigated countries were lower than 1.Therefore, coffee and coffee-based products were not dangerous to health.Our results were consistent with the results of other authors.Arvay et al. reported in the risk assessment of metals in coffee brands reported that Arabica was safe for consumers ( Arvay et al. 2019).Mushtaq et al. indicated that the concentration of Cd and Pb metals in coffee was not significant.Therefore, drinking coffee has no risk for the consumer.However, it should be mentioned that long-term exposure can be harmful to the body (Mushtaq et al. 2012).It must be remembered that other contact routes for example, dermal, inhalation, and ingestion of other sources are effective on the health risk of the consumer (Rahimi et al. 2021, Ghane et al. 2022).

Conclusion
This study was conducted to study the level of the metals in coffee and coffee-based products according to metals type and countries in various continents.Health risk of metals was also assessed based on the consumption of coffee and its metals content in different countries.According to findings, the highest content of Cd and Pb were reported in bean and infusion coffee, and the lowest content of those was detected in powder and bean coffee respectively.Concerning the trace elements, the highest concentrations of Zn, Cu, and Fe were observed in process, process, and ground coffee respectively.Moreover, considering the type of continents the highest concentrations of Cd and Pb were related to SEARO and EURO while the highest concentrations of Fe, Zn, Cu, and Ni (18.064 mg/kg) were related to PAHO, PAHO, PAHO, and EMRO respectively.The risk assessment results showed that the highest and lowest non-carcinogenic risk of metals for coffee was related to Brazil and Pakistan respectively.Based on risk assessment consumption of coffee was safe and does not pose risk to the health of consumers.The characteristics of metals and climatic, soil situations (humidity, pH, and water level), the existence of industries and active mines, type and amount of chemical fertilizers, have critical roles in the concentration of metals in coffee and coffeebased products.

Figure 1 .
Figure 1.Selection process evidence searches and inclusion.

Table 1S .
The included studies werepublished between 2001   and 2016 for Cu metal, between 2001 and 2020 for Fe metal,  between 2001 and 2021 for Cd metal, between 2001 and  2016 for Ni metal, between 1974 and 2021 for Pb metal, and  between 2001 and 2016for Zn metal.Moreover, the sample size of included articles was a total of 275 samples for Cd, a total of 1354 samples for Fe, a total of 318 samples for Ni, and a total of 654 samples for Zn.The ranking of countries based on number of the study was Poland (11 studies)

Table 1 .
(Malec and Borowski 2017)e weChandravanshi 2011)erences in metal concentrations between the types of studied coffees.The ranking of metal concentration in different coffees was Fe > Zn > Cu > Ni > Pb > Cd in powder, Fe > Cu > Zn > Ni in the ground, Fe > Zn > Ni > Cu > Pb > Cd in processed and infusion, and Fe > Zn > Ni > Cs > Pb in the bean.Based on the findings, the maximum concentrations of Cd and Pb were reported in bean and infusion coffee (0.100 and 0.695 mg/kg, respectively).The lowest concentrations of these metals were found in powder and bean coffee (0.002 and 0.033 mg/kg, respectively).About the trace elements, the maximum concentrations of Fe, Zn, and Cu were observed in the process, and ground coffee (45.788 mg/kg, 26.109 mg/kg, and 10.527 mg/kg, respectively).Besides, the lowest Fe, Zn, and Cu were seen in infusion, ground, and processed coffee (6.028 mg/kg, 4.472 mg/kg, and 0.507 mg/kg, respectively).Meta-analysis of concentration of heavy metal (PTEs) (mg.kg) in coffee and coffee-based products based on type of metals.Also, the maximum and minimum concentrations of Ni were found in processed and powder coffee (1.511 mg/kg, and 0.952 mg/kg, respectively).Numerous studies have been performed on the concentration of metals in different coffees in several countries.For example,Ribeiro et al. (2003)indicated the average concentrations of Cu and Fe in powdered coffee as 0.584 and 32.6 mg/kg, respectively(Ribeiro et al. 2003).This is possibly owing to the formation of strong complexes of ions of Cu and Fe with caffeine or other alkaloids.However, other mentioned metals make less strong attachment to the coffee matrix(Santos et al. 2004, Ashu andChandravanshi 2011).Based on the chemical properties of the different farming soils in different weather conditions, Al-Dalain, et al. reported a significant correlation between elements in the soil of cultivated coffee in various areas(Al-Dalain et al. 2020).Da Silva reported a high concentration of Pb in coffee produced in Brazil.This was related to the soil pollution in this area (da Silva et al. 2017).Malec et al. reported the varied level of heavy metals in the plant based on the character and the pollution resource of soil.Metals in the soil in a dissolved form can be absorbed by plants, accumulated in plant tissues, and transferred to coffee(Malec and Borowski 2017).Based on the species of coffee plant cultivation, Novozamsky et al. indicated the different chemical con- (Novozamsky et al. 1993) and Copper (Cu), Nickel (Ni) Iron (Fe) and zinc (Zn),.ively(Trindadeetal. 2020).Based on the results of our metaanalysis and published studies by others, large variability in metal concentrations metals(Fe, Cu, Ni, Zn, Cd, and Pb)within coffee consumption (powder, ground, processed, infusion, and bean) can be caused by the differences in the physicochemical properties of metals, as well as the conditions and species of coffee plant cultivation (Wasserman 1998).It was revealed that the types of soil (organic and mineral content, drainage status, pH, and water level) fertilizer, and pesticides used in coffee cultivation affect the metal content in coffee(Martı n et al. 1998).Considering various chemicalphysical properties of metals, Santos et al. showed higher extractability for Ca, Mn, Mg, and Zn metals as compared to Cu and Fe metals.tent of metals in coffee at different sites.It can be related to various genotypic of the coffee plant, which may selectively accumulate nutrients.Thus, a balance is made between intracellular content to improve metabolism, various protein synthesis, and tissue production(Novozamsky et al. 1993).Based on the fertilizer and pesticides used in coffee cultivation, Morgano et al. obtained different values of Cu associated with the origin pesticides, and agricultural treatment

Table 2 .
Meta-analysis of concentration of toxic metal (PTEs) (mg.kg) in coffee and coffee-based products based on WHO regions.European Region; c Eastern Mediterranean Region; d The Pan American Health Organization; e South-East Asia region.

Table 3 .
Uncertainty analysis for TTHQ of metals in adult due to consumption of coffee and coffee-based products in various countries.
b Total ingestion rate.