Introduction:

Coffee belongs to the scientific family called Rubiaceae or genera Coffea, which comprises around 70 different species [1, 2]. Among the species, Coffea arabica which contributes around 75 % of the world's production, and Coffea canephora which contributes around 25 % are commonly available on the world market [3, 4]. Coffee is one of the most important agricultural products in the international business in terms of international trade. It is the second most product in value after petroleum in international trade [5]. Coffee is the top consumed beverage after water in the world. Around 500 billion cups of coffee are drunk per year through out the world [6, 7]. Around 40% of the world's population is a coffee consumer and drinking coffee is a part of their daily lifestyle and habit for most people in the world [3]. From a historical point of view, coffee consumption began in Ethiopia, where the local people have been drinking coffee for many centuries [8]. Ethiopia is the place of origin of coffee, and then coffee made its way to Yemen possibly around the 6th century, and then spread throughout the world [9].

Coffee is the major source of the Ethiopian economy as it contributes over 60% of the national foreign exchange earnings and it covers 30% of government direct revenue [8, 10]. Metu, Jimma, Yirgachefee, Sidama, Harare, and Wolega are the leading coffee producing areas in Ethiopia [8]. Brazil, Vietnam, Colombia,  Indonesia, and Ethiopia are the largest coffee producers in the world [2, 11]. Ethiopia, Uganda, Côte d’Ivoire, Zimbabwe, Kenya, Tanzania, Rwanda, Angola, Cameroon, and Burundi are the biggest coffee producers in Africa [12]. The coffee beverage can be consumed for many reasons. The popularity of coffee is due to caffeine, a naturally-occurring alkaloid compound which has an energetic and stimulating value, it has antioxidant properties. In addition, the importance of coffee is associated with a decreasing risk of several diseases. The consumption of coffee can lower the risk of depression in women due to the presence of caffeine and therefore, drinking more than four cups of coffee per day can decrease the probability of attacking by hypertension, while the ingestion of more than seven cups per day reduces even further the risk of type 2 diabetes [3]. Caffeinated coffee also has the benefit of lowering the risk of death from Parkinson's disease in men and women who never used postmenopausal estrogens [13] since it is an important source of daily needs of several essential elemental nutrients like Na, Mg,  K, Ca, Cl, Fe, and Mn [13].

As coffee consists of essential elements, it may also contain an excess of toxic metals that can cause public health risks. Heavy metals are metals that have a specific density of greater than 5 g/cm³ [14, 15]. These metals are essential to maintain various biochemical and physiological functions in living organisms. However, they become a risk to human health when their concentration is found above a certain permissible limit [16]. Chromium, arsenic, lead, cadmium, copper, zinc, and nickel are the most common heavy metals [16, 17].

Inhalation and ingestion are the two main routes in which humans get exposed to those heavy metals. The toxic metals are distributed and found in the soil, water, rock, and air. Plants, vegetables, and fruits then gradually take up these metals through root absorption which get accumulated in them [16, 18]. Eating these plant and animal sources, drinking water, breathing the polluted air, and or smoking cigarettes are the means by which humans and animals are exposed [7]. However, eating poisoned food is the main source of toxic metals for humans [14]. Soil erosion, natural weathering of the earth’s crust, mining, wastewater from various industries, urban runoff, sewage discharge, herbicides and pesticides, fossil fuels,  fertilizers, and insect or disease control agents applied to crops are the major sources of heavy metal poisoning [16, 19].

Figure 1: The sources of heavy metal in the environment [20].

The foods and drinks that a person takes may contain both essential and toxic elements. The essential mineral elements Na, Mg, Cl, K, Ca, and Mn are important for healthy growth, development, and the proper functioning of the human body [21, 22]. They have an important role in bone and tooth formation and normal nerve function [23]. They are the sources of energy and the storage of carbohydrates. But toxic metals in the body when excess amounts are ingested, can induce adverse health effects. Exposure to toxic metals is responsible for damage to vital organ systems, adverse effects on cognitive abilities and the reproductive system, induces diseases such as multiple sclerosis and Alzheimer’s disease. According to the International Agency for Research on Cancer (IARC), toxic metals are classified as a category of carcinogens, as they increase cancer risk (kidney and liver) in humans even with mild to moderate exposure, since they damage cells or DNA [23]. Heavy metals beyond the permissible limits also lead to illness in human fetuses, preterm labor, and mental retardation in children. Adults may suffer from fatigue, high blood pressure, and kidney problems [24]. And therefore, the World Health Organization (WHO) and the Food and Agricultural Organization of the United Nations (FAO) have set guideline standards including maximum permissible limits (MPL) for toxic heavy metal contents in food and beverage varieties [25]. Abnormalities in human health may be caused by the deficiency or excess of various elemental nutrients in the environment [26]. It implies that the concentration of heavy metals in air, water, and food varieties should be studied to avoid their harmful effects. Since coffee is consumed throughout the world, the nutritional quality of the species should be investigated. That is, the amount of essential and non-essential elements has to be determined and kept under consideration [3]. For the analysis of coffee, different analytical techniques can be used,  like inductively coupled plasma mass spectrometry (ICP-MS), and neutron activation analysis (NAA) [8, 13].

Materials and Methods:

Strong acids like nitric acid, hydrogen peroxide, distilled water, beakers, tubes, or vessels, full setup of ICP-MS, and standard sample solution.

ICP-MS Method:

Everything around us, including human beings, is made of different combinations of elements. If one needs to identify from which elements something is made, a technique called inductively coupled plasma mass spectrometry (ICP-MS) can be used [27, 28]. It is a relatively young technique that was invented at the beginning 1980s and for the first time commercially available in 1983 by Perkin Elmer SCIEX [29]. ICP-MS is a fast, multi-elemental analysis technique of a given sample. It can detect metals and non-metals in a liquid sample at a very small sample size [30]. This technique performs both qualitative and quantitative multi-elemental analysis of a liquid sample [29]. 

High sensitivity, low detection limit, high resolution, taking small sample amounts, simultaneous multiple element detection, fast scanning characteristics, and isotope quantification of various elements are the characteristics that make inductively coupled plasma mass spectrometry the most advantageous technique [28, 29]. However, the occurrence of spectral and non-spectral interference of ions, its destructive nature, its uses of only liquid samples, and its high cost are the major disadvantages of ICP-MS  [31]. The principle behind ICP-MS is based on ionizing various atoms in the prepared liquid sample using the extremely hot temperature from the plasma torch created from argon gas. Those ions are detected and separated by a mass spectrometer (MS) according to their mass-to-charge ratio [30].

The fundamental components of ICP-MS include the sample introduction system, inductively coupled plasma (ICP), interface (sample cone and skimmer cone), ion optics (electrostatic lenses), a mass analyzer, detector (electron multiplier EM), and the appropriate software [29, 32].

The initial step in the analysis of the sample is the introduction of the liquid sample. The common way of sample introduction is the use of an analytical nebulizer. The prepared sample solution is pumped into a nebulizer [32]. Then it converts the liquid into a fine spray or aerosol mist (droplet form). The aerosols are then passed through a spray chamber which is another part of ICP-MS where the larger droplets are removed (selection) and the appropriate aerosol can then be swept into the plasma torch to create the ions [33].

In a plasma torch, argon which is the ionizing gas of inductively coupled plasma mass spectrometry (ICP-MS), is exposed to a high energy which is generated from coils based on electromagnetic induction using Faraday-Lenz’s law, and hence the gas is now converted into a plasma of temperature at approximately 7,500–10,000 K [29] which is hotter than the surface of the sun. The sample aerosol is put through the center of the plasma where the droplets are dried and the sample material is decomposed and dissociated into individual atoms [27]. The atoms are then ionized (M → M⁺ + e⁻) so that they can be detected and separated by the mass spectrometer [34].

The next part of inductively coupled plasma mass spectrometry (ICP-MS) is an interface (sampler Cone and skimmer cone). They are parts in which the free ions generated by the plasma torch are transmitted to the mass spectrometer (in a vacuum chamber). The motion of the free ions is adjusted by electrostatic lenses or optical lenses. The lens is composed of several metal plates with adjustable voltages applied to them. A plate with a positive voltage repels the positively charged ions. While a plate with a negative voltage attracts the positive ions [33]. The purpose of electrostatic lenses or optical lenses is to focus (positive) ions onto the entry of the true mass spectrometer. In addition to focusing, the ion lens also separates the generated ions from the neutral particles and photons extracted from the plasma. These uncharged particles are the sources of noise or background signal and signal instability, so they must be prevented from passing and reaching the detector. Since they are uncharged, they continue in a straight line rather than attracted by the plates and so they are removed from the ion beam [28].

Collision or reaction cell is also another component of inductively coupled plasma mass spectrometry (ICP-MS). It is used to resolve ion overlaps or to prevent ion combinations to form polyatomic ions. It prevents ion interference [30]. Example ⁴⁰Ar can combine with ¹⁶O to create an ArO⁺ polyatomic ion at a mass of 56 which is overlapping with the major isotope of iron (⁵⁶Fe). So interference occurs by ArO+ and Fe.

Those generated ion beams are now forwarded into the basic components of ICP-MS called Mass Spectrometer (MS) or mass analyzer. It filters and sorts identical ions by mass or more accurately, by mass-to-charge ratio (m/z). The quadrupole type of mass analyzer consists of four parallel cylindrical metallic rods [28]. Radio-frequency alternating current (AC) and direct current (DC) potentials are applied to the rods, creating a time-varying electric field in the center through which ions pass. For an ion with a particular m/z ratio, only specific combinations of AC and DC potentials result in a stable ion flight trajectory through the quadrupole [27].

The quantity of the separated ions of various atoms is processed and counted using the common detector used in ICP-MS called an electron multiplier (EM) [35]. The electron multiplier detector consists of a series of sensitive dynodes. Positively-charged analyte ions strike the first dynode,  which allows them to generate more secondary electrons. Each ion that strikes a dynode releases more electrons further and finally, a cascade of electrons is formed. Which generates a signal pulse. This process makes the signal large enough to be measured as an ion count. There are many ions of the same element. For each ion measured, the counts are registered by the detector which is processed, and a spectrum is formed which is the mass to charge (m/z) ratio of the ions present in a sample against their intensities. The calculation of the width or area of the peak is made using data analysis software that can give the concentration of the elements in the sample [34].

Figure 2: The main components of ICP-MS [28].

Health Risk Assessment:

The associated health risk of coffee can be expressed in terms of quantities called Estimated Daily Intake (EDI) and Chronic Daily Intake (CDI) [6]. The value of Estimated Daily Intake (EDI) and Chronic Daily Intake (CDI) should be below the oral reference dose (RFD). Maximal estimated daily intake (EDI) is calculated in adults of average body weight (BW) of 70kg using mass consumed (MSi) of 5 g for coffee as [6].

EDI =                                                                  Eq .1

Where C represents the concentration of each toxic element in the sample. The chronic daily intake (CDI) can be calculated as [6, 40],

CDI =                                                     Eq .2

Where EF is exposure frequency which is considered as every day of the year (365 days/year), EDtot is the total exposure duration, in most countries a person starts drinking coffee at the adult stage (18 years) and continues up to his/her death. The average life span in the world is 74 years, and therefore,  EDtot is 56 years, and AT is the average period of exposure (365 days/year).

The Target Hazard Quotient (THQ) of each toxic element can be calculated as,

THQ = CDI/RFD                                                                    Eq .3

Hazard Index (HI) determines the total risk of all toxic metals in the sample.

HI =                                                                                     Eq .4

An HI value less than 1 is accepted whereas HI > 1 is a danger that can cause adverse health effects.

Results:

The elemental analysis of different element concentrations in a coffee sample is measured in the Czech Republic using inductively coupled plasma mass spectrometry (ICP-MS) which was imported from Ethiopia [5]. The aim was to determine the mineral nutrient contents like Ca, Cu, Fe, Mg, Zn, Cd, Cr, Mn, Ni, and Pb in five types of imported coffee from different countries and to compare them in terms of elemental content.

         Table 1: Average concentrations (in μg/g) of selected metals in Ethiopian coffee using ICP-MS.

LOD – limit of detection, ND- Not Detected

Discussion:

The findings of [5] in Table 1 show that coffee of Ethiopian origin contains essential elements such as Mg, Ca, Mn, Fe, Co, Cu, and Zn [36] which are important for living organisms for the growth and health of living and also non-essential and toxic elements like Cd, Cr, and Pb [19] which become toxic at high concentration. The result shows different elemental concentrations in Ethiopian coffee. This variation might be due to the type of soil where the coffee was cultivated. Soils are also the main source of heavy metals in plants, where they become the main source of heavy metals in plant-derived foods [36]. Some coffees are grown on soil exposed to fertilizers, pesticides, and other agrochemical. Similarly, a coffee plant cultivated on land exposed to wastewater from industry and urban areas may contain several water-soluble toxic metals.

In terms of the concentration value, the experimental result shows that the most dominant heavy metal is manganese, which was found to be the maximum, followed by copper and zinc respectively as shown in Table 1. Manganese is within permissible limits and will not have adverse effects. It is essential for the development of normal bone structure, reproduction, metabolism of amino acids, lipids, carbohydrates, and functioning of the central nervous system [22]. The kidney and liver are the main storage places for the manganese in the body. But excess manganese is toxic to humans [19]. The result of the paper shows that the concentration of manganese is found to be lower in contents than the allowed maximum limits set by FAO and WHO jointly as shown in Table 2. The concentration of copper is found to be  17.64 ± 1.25μg/g from the Ethiopian coffee sample which is under the maximum permissible concentration. Headaches, fatigue, insomnia, depression, hypotension, skin rashes, spaciness, or detachment are the symptoms caused by copper poisoning [14].
On comparing the metallic concentration of Zinc in a coffee with those proposed by FAO/WHO it was found that its concentrations fall within the permissible limit. Zinc is one of the most important minerals in the body. It is used to govern the contractibility of muscles,  acts as a co-factor for enzymes, takes part in the synthesis of DNA, and insulin biosynthesis [19]. The concentration of nickel in the coffee sample is 0.460 ± 0.02 μg/g which is lower than the permissible limit set by FAO/WHO  in medicinal plants, which is 1.63 μg/g as shown in Table 2. Excess nickel is carcinogenic and can cause cancer of different organs such as the nose, prostate, and lungs [19].
Chromium(Cr) is involved in natural human lipid and protein metabolism, so that very small amounts are needed for normal human life functions. Excess chromium causes asthma, shortness of breath, liver and kidney damage, and allergic reactions [36]. The amount of cadmium(Cd) content in the Ethiopian coffee sample is 0.040 ± 0.01 μg/g which is within the permissible values recommended by FAO and WHO jointly. Contamination of food and beverages with Cd is of high health risk, which is classified in Group I of human carcinogens by the International Agency for Research on Cancer (IARC) [37]. It is an extremely toxic metal. Its permissible value recommended by FAO and WHO jointly is 0.3 μg/g as shown in Table 2 which is the lowest limit due to its adverse effect. The concentrations of lead in the coffee samples fall within the permissible limit. Therefore, its consumption will not lead to any negative effect on human health.

Table 2: Maximum Permissible Limit values for toxic metals in medicinal plants according to [38].

In the present study, the values of Estimated Daily Intake (EDI) and Chronic Daily Intake (CDI) for each element are calculated to estimate the health risk associated with the consumption of coffee as shown in Table 3, and the values are found to be in agreement with the oral reference dose (RFD) set by the US, EPA. The values of THQ and HI are also found to be less than one which means that the risk of developing diseases connected with chronic exposure to heavy metals consumed with coffee is low.

     Table 3: The health risk assessment of heavy elements through coffee consumption.

Conclusion:

Coffee is the most popular and appreciated beverage all around the world, mainly for its stimulating properties and the advantage of decreasing the risk of various diseases. It originated in Ethiopia, which is the leading coffee producer country in Africa. As coffee contains essential elements, it may also contain an excess amount of toxic metals that can cause public health risks. The concentration of toxic elements like lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), manganese (Mn), zinc (Zn), cobalt (Co), and chromium (Cr) in Ethiopian coffee was determined by a fast and multi-elemental analysis technique called inductively coupled plasma mass spectrometry (ICP-MS). The amount of those toxic elements is found to be below the maximum permissible values set by FAO and WHO jointly. Furthermore, the values of Estimated Daily Intake (EDI) and Chronic Daily Intake (CDI) for each element are found to be in agreement with the oral reference dose (RFD) set by the US, EPA. The values of the Target Hazard Quotient (THQ) and Hazard Index (HI) are also found to be less than one and therefore, the consumption of Ethiopian coffee will not lead to any negative effect on human health.

Conflict of Interest:

The authors declare that the research is free of any financial relationships that could be construed as a potential conflict of interest.

Data Availability Statement:

The primary data supporting this SYSTEMATIC REVIEW are from previously reported studies and datasets, which have been cited.