Abstract
Introduction
Tea consumption with meals affects iron absorption, increasing the risk of iron deficiency. Our study investigated the association between tea consumption patterns and serum ferritin levels among women of childbearing age (WCA) in Nandi County, Kenya.
Methods
We conducted a cross-sectional analytical study among 160 WCA selected using a systematic random sampling technique from Kapsabet Ward. Information on tea consumption practices was gathered using a researcher-administered questionnaire, and serum ferritin and C-reactive protein were measured. We assessed associations between tea consumption and iron status of respondents by multivariable regression analysis, adjusting for potential confounders, including parasitic infections and recent severe blood losses.
Results
The prevalence of anaemia and iron deficiency among the study participants were 86.2% and 45%, respectively. Majority (90.6%) of the respondents consumed tea or coffee, with an infusion time of more than 5 min (60.0%) and a moderate tea strength (64.1%), within 1 h before or after meals. Iron deficiency was associated the number of teacups consumed (adjusted odds ratio = 7.282, 95% CI = 3.580–14.812).
Conclusion
High tea consumption is positively associated with iron deficiency among WCA. Lower tea infusion strength, shorter tea infusion duration, and a lower number of teacups overall consumed, as well as consuming tea 1 h before or after meals instead of with meals, may be recommended for better outcomes in iron status among WCA.
Keywords: Serum ferritin, Tea consumption patterns, Polyphenols, Iron status, Women of childbearing age
Introduction
Kenya is the third leading producer of tea worldwide after China and India [1]. Tea is the second most popular beverage globally after packaged water [2]. Much lobbying has been undertaken to promote tea consumption among the local Kenyan people. As such, Kenya has seen a tremendous increase in the consumption of tea for over 2 decades [1, 3]. A Kenyan adult is reported to take 2–3 cups of tea for breakfast daily [4]. Furthermore, high consumption of tea among pregnant women has been reported, although the intake of tea is relatively low among youths aged between 15 and 25 years [5]. A growing body of evidence postulates that women of childbearing age (WCA) consume tea with meals in Kenya [6–10], or close to mealtimes, within less than 20 min before or after meals [11].
The effect of tea consumption on iron absorption has been investigated extensively in various populations. A study conducted in the UK described that the simultaneous consumption of tea and an iron-containing porridge meal resulted in a notable decrease in nonheme iron absorption among women [12]. In Morocco, results of a randomised controlled trial indicated that tea consumption might reduce iron absorption from NaFeEDTA by more than 85% in both women with iron deficiency anaemia and non-anaemic women [13]. Using rice meal, an Indian RCT found that the consumption of 1 or 2 cups of tea resulted in a reduction in iron absorption by 49% or 66%, respectively, and in the IDA group by 59% or 67%, respectively [14]. Contrasting findings emerged from a study conducted in South Africa, which found that tea consumption did not significantly increase the risk of iron deficiency in a mixed black adult population [15]. This assumption was confirmed in studies conducted in Western populations with generally adequate iron stores, where tea consumption did not influence iron status [16, 17].
Plant-based food sources such as wine, tea, and coffee contain polyphenols [18]. The most abundant phenols in tea are catechins and tannins [16]. Phenols significantly reduce the dietary bioavailability of iron by inhibiting iron absorption from many meals in the gut. Tea consumption patterns, including the type of tea, frequency, steeping duration, and timing of consumption, may be determining factors in the potential effect of tea on iron status. Habitual tea consumption during meals might pose a significant risk of chronic depletion in iron stores if appropriate interventions are not implemented [19, 20]. Therefore, investigating the association between tea consumption patterns, encompassing aspects such as the type of tea, frequency, steeping duration, and timing of consumption, is key to understanding the link between tea consumption patterns and iron status. Iron deficiency is more pronounced among WCA [21]. However, most studies have primarily focused on assessing dietary iron intake, with less emphasis on investigating the consumption patterns of iron absorption inhibitors, specifically among WCA. To address this gap, the present study aimed to examine the relationship between tea consumption patterns and iron status among WCA in Nandi County.
Methods
A cross-sectional analytical study was conducted in December 2019 among WCA drawn from Kapsabet Ward of Emgwen Sub-County in Nandi County, Kenya. The study area is located in the western region of Kenya, which has a subtropical highland climate. The area is characterised by hilly terrain with fertile soils, making it suitable for tea cultivation. Income is mainly agricultural, with tea farming being a major source of income for many households. Kapsabet Ward covers Kapsabet town which serves its dwellers within a radius of 5–10 km. The residents either purchase their tea from three tea factories in the ward or from retail shops in Kapsabet town.
Non-expectant and non-lactating WCA aged between 15 and 49 years who consented to participate in the study were included in this study. Those respondents who had taken iron supplements in the past 6 months, donated blood or suffered severe blood loss in the previous 6 months, or had other chronic illnesses were excluded from the study. Our primary outcome was serum ferritin (SF) levels. Participants were classified as iron deficient when their SF was <15 μg/L or SF 15–70 μg/L and C-reactive protein (CRP) >5 mg/L [22, 23], and all other participants were considered to have normal iron status.
Sample Size Determination and Sampling Technique
G Power software version 3.1.9.4 was used to determine the sample size. The level of significance (α) was 0.05, while the level of power (1-β) was 0.95, and the odds ratio was 3.57 with a proportion of successful outcome among the tea/coffee consumers (Pr(y = 1|x = 1) = H1) of 0.65 and proportion of successful outcome among the non-tea/coffee consumers (Pr(y = 1|x = 1) = Ho) at 0.35 [24]. A sample size of 160 was determined allowing 10% non-response [24].
Kapsabet Ward has eight villages (online suppl. Material; for all online suppl. material, see https://doi.org/10.1159/000536196) with a total target population of 4,960. A proportionate sample was determined for each village, and a systematic sampling technique was employed to select respondents at the village level. The households were mapped and numbered systematically. The selection interval ranged from 29th to 32nd households in the respective villages with the first household determined using a simple random sampling technique. For households that had more than one eligible respondent, an online random number generator was used to settle on one participant.
Data Collection Tools and Methods
A structured, researcher-administered questionnaire was used to collect information on the tea consumption patterns of the respondents. The tool was used to collect data on the common type of beverage consumed, reasons for taking or not taking tea/coffee, types of tea, preferred flavour, accompaniment, a household measure of a teacup, number of teacups consumed, tea infusion time, strength of tea in teacups, and time WCA took tea (before, after, or with meals). Three scales of tea strength based on infusion time used are low (less than 2 min), moderate (2–5 min), and high (more than 5 min), representing lighter, medium, and richer levels of colours, respectively (online suppl. Material) [25].
Pre-testing of the questionnaire was carried out among 10% of the sample size [26], selected from Emgwen Sub-County, before the actual data collection. We modified the content of the data collection tool based on the findings of the pre-test and expert consultations to ensure validity. The reliability of the tool was ensured through the test-retest method, and the questionnaire was administered twice with a difference of 2 weeks, and the Cronbach coefficient was 0.8.
Seven undergraduate nutrition students and three phlebotomists were trained by PNN in data collection and blood collection procedures, respectively. Training included demonstrations and role-plays to improve data collectors interviewing skills. Members of the data collection team resided in Kapsabet town, spoke fluent Nandi (local language), and were well versed in local Nandi culture and setting. During the data collection process, PNN provided supervision to each group of data collectors. These groups, comprising a phlebotomist and two interviewers, were assigned to specific villages. The paper questionnaire was filled by the trained research assistants after collecting information directly from participating WCA.
Collection of Blood Sample
A phlebotomist drew 2 mL venous blood from participants aseptically; half ml of the collection was aliquoted into BD vacutainer tubes (purple tubes) with K2E anti-coagulant for haemoglobin determination within 24 h of collection and the rest into serum vacutainers. Samples were coded for identification, using a fine-point permanent marker pen. The tubes were packed in a cooler box at 15°C and transported within 1 h of collection to Chepsoo Medical Centre, and they were centrifuged, serum separated (maximum time: 60 min), aliquoted into vials, and refrigerated at 4°C for 5 days. A 5-day collection of serum was packed in a cooler box at 15°C and transported (maximum time: 7 h) to the University of Nairobi/Kenyatta National Hospital Paediatric laboratory where they were stored at a temperature below −20°C (the biomarkers are stable for 12 months in this temperature). Repeated cycles of freezing and thawing were avoided to reduce interference with the integrity of the samples. Analyses for SF and CRP were conducted after 1 month of sample storage in the frozen state.
Biomedical Methods for Determining Biomarkers
Blood in vacutainers with K2E anti-coagulant was used to form a drop that was placed on a strip inserted in the Mission® Plus machine (San Diego, USA) for haemoglobin determination. SF was quantitatively determined using an automated chemiluminescence LIAISON® analyser (DiaSorin S.p.A., Saluggia, Italy). CRP was analysed using an automated HumaStar 600 quantitatively by the immunoassay method. The standards were stored for 2 days at a temperature of 2–8°C. During biochemical analysis, the SF samples were first retrieved from storage, defrosted, and thoroughly mixed using a vortex mixer.
Data Analysis
Data were cleaned and coded. Data on tea consumption patterns, biomarkers, and health-related data were entered into Statistical Package for Social Sciences software version 22 (Illinois, Chicago). Descriptive statistics, such as percentage, means and standard deviation, were performed on tea consumption patterns and iron status. Multivariable regression was conducted to determine the association between tea consumption patterns and iron status (as a dichotomous variable) of WCA [15]. Seven respondents were excluded from the final multivariable analysis to control for malaria and severe blood losses (two had recent episodes of malaria, three had recent severe blood loss, and one had both) (online suppl. Material). The consumption of milk and milk products with meals were adjusted for during the final (regression) analysis.
Results
Characteristics of the Study Respondents
A total of 160 WCA participated in the study. Data and blood samples were obtained from all of them. Table 1 presents the socio-demographic characteristics of the study respondents. Majority of the respondents were single (57.5%) with a mean age of 24.7 years (SD: 7.31). A total of 145 WCA reported to be tea/coffee consumers. Finally, 139 WCA were included in the analyses. Reasons for exclusions are shown in online supplementary Figure 1.
Table 1.
Socio-demographic characteristics of the respondents
| Characteristics | n = 160, n (%) |
|---|---|
| Sex of household head | |
| Male | 77 (48.1) |
| Female | 83 (51.9) |
| Marital status | |
| Single | 92 (57.5) |
| Married | 65 (40.6) |
| Separated | 2 (1.3) |
| Widowed | 1 (0.6) |
| Age, years | |
| Mean age (SD) | 24.7 (7.31) |
| 15–24 | 86 (53.8) |
| 25–34 | 56 (35.0) |
| 35–44 | 16 (10.0) |
| 45–49 | 2 (1.3) |
| Highest education level attained | |
| No formal education | 2 (1.3) |
| Primary | 48 (30.0) |
| Secondary | 69 (43.1) |
| Tertiary | 41 (25.6) |
| Occupation | |
| Casual worker | 27 (16.9) |
| Formal employment | 14 (8.8) |
| Businessman/woman | 44 (27.5) |
| Student | 67 (41.9) |
| Others | 8 (5.0) |
Tea Consumption Patterns among the Study Respondents
The tea consumption patterns of the study respondents are presented in Tables 2 and 3. Tea or coffee was the most consumed beverage (90.6%) among the study participants. Nearly two-thirds (64.1%) of the respondents reported drinking tea with moderate infusion strength, and the majority (75.2%) consumed tea with milk. Majority (71.7%) of the respondents consumed tea with meals during breakfast and slightly more than half (53.4%) at lunch meal and over one-third (37.7%) during supper. Those who did not take tea with meals mainly consumed the tea 1 h before or less than 1 h after the meals (Table 3).
Table 2.
Consumption patterns of tea among the study participants
| Characteristics | n = 145a, n (%) |
|---|---|
| Beverage consumed (n = 160) | |
| Tea and/or coffeeb | 145 (90.6) |
| Other drinksc | 15 (9.4) |
| Reasons for taking tea | |
| Health/dietary reasons benefits | 39 (26.9) |
| To keep warm | 12 (8.3) |
| Prefer tea taste | 18 (12.4) |
| Drinking tea is relaxing | 11 (7.6) |
| Habitual | 65 (44.8) |
| Type of tea taken | |
| Black | 138 (95.2) |
| Green | 5 (3.4) |
| Blend | 2 (1.4) |
| Preferred flavour in tea | |
| Ginger/masala | 36 (24.8) |
| Lemon | 10 (6.9) |
| Plain | 98 (67.6) |
| Others | 1 (0.7) |
| Accompaniment | |
| Without milk | 36 (24.8) |
| Tea with milk | 109 (75.2) |
| Duration of tea infusion | |
| 0–2 min | 6 (4.1) |
| 3–5 min | 52 (35.9) |
| >5 min | 87 (60.0) |
| Frequency of tea consumption | |
| 1–2 times a week | 5 (3.4) |
| Breakfast only | 34 (23.4) |
| 2–3 times a day | 79 (54.5) |
| >3 times a day | 27 (18.6) |
| Volume of tea taken | |
| 200–500 | 53 (36.6) |
| 501–1,000 | 61 (42.1) |
| 1,001–1,500 | 25 (17.2) |
| 1,501–2,000 | 6 (4.1) |
| Strength of black tea concentration | |
| Low | 30 (20.7) |
| Moderate | 93 (64.1) |
| High | 22 (15.2) |
aFifteen respondents did not consume tea or coffee.
bTea was the predominant beverage among the majority of respondents, however, since coffee is equally a potential inhibitor of iron absorption and demonstrates similar inhibitory effects as tea, both beverages (tea and coffee) were included.
ci.e., cocoa/drinking cholate and juices.
Table 3.
Consumption patterns of tea among WCA in Nandi County, Kenya (n = 145a)
| Breakfast (n = 145) | Tea with breakfast | Tea before breakfast (n = 18) | Tea after breakfast (n = 23) | ||
| 104 (71.7%) | <1 hb | >1 h | <1 h | >1 h | |
| 13 (72.2%) | 5 (27.8%) | 15 (65.2%) | 8 (34.8%) | ||
| Lunch (n = 88) | Tea with lunch | Tea before lunch (n = 7) | Tea after lunch (n = 34) | ||
| 47 (53.4%) | <1 h | >1 h | <1 h | >1 h | |
| 4 (57.1%) | 3 (42.9%) | 29 (85.3%) | 5 (14.7%) | ||
| Supper (n = 77) | Tea with supper | Tea before supper (n = 7) | Tea after supper (n = 41) | ||
| 29 (37.7%) | <1 h | >1 h | <1 h | >1 h | |
| 6 (85.7%) | 1 (14.3%) | 36 (87.8%) | 5 (12.2%) | ||
aFifteen respondents did not use tea or coffee.
bAs assessed using a 1 h reference scale [12].
Iron Deficiency among WCA in Nandi County, Kenya
The prevalence of crude iron deficiency was 21.3% but increased to 45.0% after adjusting for inflammation among the respondents (Table 4).
Table 4.
Iron status of the respondents
| Parameters | n = 160, n (%) |
|---|---|
| Haemoglobin levels, g/dL | |
| Mean (SD) | 9.6 [1.9] |
| Normal ≥12.0, g/dL | 22 (13.8) |
| Mild anaemia (11.0–11.9 g/dL) | 24 (15.0) |
| Moderate anaemia (8.0–10.9 g/dL) | 86 (53.8) |
| Severe anaemia (<8 g/dL) | 28 (17.5) |
| Anaemia (<12.0 g/dL) | 138 (86.2) |
| C-reactive protein (CRP) concentrations, mg/L | |
| Mean (SD)a | 4.826 [2.017] |
| Elevated levels (CRP >5 mg/L) | 49 (30.6) |
| Serum ferritin (SF) concentrations, µg/L | |
| Mean (SD) | 35.3 [42.2] |
| Crude iron deficient storesb | 34 (21.3) |
| SF 15–70 µg/L and CRP >5 mg/L | 38 (23.8) |
| Adjustedc iron stores status | |
| Iron deficient (ID)d | 72 (45.0) |
| Frequency of deworming (n = 94) | |
| Regularly (every 3 months) | 48 (51.1) |
| Irregularly | 46 (48.9) |
| Had malaria episode within 2 weeks preceding data collection | 3 (1.9) |
| Had recent (<3 months) severe blood loss | 5 (3.1) |
aStatistical measure is mean and standard deviation.
bCrude Iron deficient stores is SF <15 µg/L.
cAdjusted iron stores for inflammation.
dID is (SF <15 μg/L or SF 15–70 µg/L and CRP >5 mg/L).
Association between Consumption of Tea and Iron Deficiency
An increase in the number of teacups consumed was associated with an increased likelihood of iron deficiency among the respondents (adjusted odds ratio (AOR) = 7.282, 95% confidence interval (CI) = 3.580–14.812, p < 0.001). Low compared to high tea infusion strength in teacups (AOR = 0.060, 95% CI = 0.060–0.270, p < 0.001) or short (3–5 min) in comparison to long (more than 5 min) duration of tea infusion (AOR = 0.318, 95% CI = 0.318–0.144, p < 0.001) were less associated with iron deficiency (Table 5).
Table 5.
Association between consumption patterns of tea and serum iron statusa among WCA in Nandi County, Kenya
| Determinants | CORb [95% CI] (n = 145) | p value* | AORc [95% CI]d (n = 139) | p value* | SF, µg/L | |
|---|---|---|---|---|---|---|
| mean (SD) | 95% CI | |||||
| Accompaniment | ||||||
| Tea (without milk) | 0.055 [0.006–0.505] | 0.010 | 0.044 [0.005–0.413] | 0.006 | 37.453 (35.696) | 27.252–50.553 |
| Tea (with milk) | 0.080 [0.009–0.687] | 0.021 | 0.070 [0.008–0.605] | 0.016 | 40.423 (56.161) | 29.763–56.198 |
| Tea (without milk) with food | 0.143 [0.016–1.290] | 0.083 | 0.134 [0.015–1.218] | 0.074 | 29.318 (27.152) | 20.515–40.134 |
| Tea (plus milk) with food (ref) | 0.031 | 0.017 | 15.962 (8.260) | 10.120–22.298 | ||
| Duration of tea infusion | ||||||
| 0–2 min | 0.512 [0.089–2.940] | 0.453 | 0.098 [0.98–3.250] | 0.502 | 36.167 (22.914) | 19.925–56.729 |
| 3–5 min | 0.341 [0.160–0.726] | 0.005 | 0.318 [0.318–0.144] | 0.005 | 44.578 (63.416) | 30.068–62.885 |
| >5 min (ref) | 0.019 | 0.018 | 30.239 (28.090) | 24.981–36.789 | ||
| Tea infusion strength in teacupse | ||||||
| Low | 0.052 [0.012–0.231] | <0.001 | 0.060 [0.013–0.270] | <0.001 | 38.420 (24.900) | 30.398–48.102 |
| Moderate | 0.352 [0.131–0.945] | 0.038 | 0.366 [0.133–1.006] | 0.051 | 37.040 (51.531) | 27.806–49.902 |
| High (ref) | 0.001 | 0.001 | 25.325 (29.581) | 15.495–39.902 | ||
| Frequency of tea intake | ||||||
| 1–2 times a week | 0.999 | 0.999 | 159.840 (155.410) | 51.576–330.400 | ||
| Breakfast only | 0.997 | 0.997 | 52.062 (38.536) | 39.773–66.430 | ||
| 2–3 times a day | 0.026 [0.003–0.203] | <0.001 | 0.023 [0.003–0.179] | <0.001 | 27.636 (16.570) | 24.032–31.685 |
| >3 times a day (ref) | 0.005 | 0.005 | 13.127 (6.156) | 10.966–15.671 | ||
| No. of cups (250 mL) per dayf | 7.300 [3.643–14.626] | <0.001 | 7.282 [3.580–14.812] | <0.001 | ||
aThe iron status indicator was SF levels.
bCOR stands for crude odds ratio.
cAOR stands for adjusted odds ratio.
dAdjusted for parasitic infections, severe blood losses, and milk and milk products.
eLow, moderate and high tea infusion strength is define by short (<2 min) and lighter colour, moderate (2–5 min steeping) timing and moderate colour intensity, long (>5 min) and richer colour, respectively.
fThe consumption of tea also caters for the infrequent consumption of coffee by the respondents.
*Significance level at p < 0.05.
**A multivariable logistic regression model was used.
Discussion
This cross-sectional analytical study conducted among 160 WCA from Nandi Country, Kenya, investigated the relationship between consumption patterns of tea and iron status. The prevalence of iron deficiency among the study participants was 45%. Majority of the respondents consumed tea or coffee, with an infusion time of more than 5 min (60.0%) and a moderate tea strength (64.1%), within 1 h before or after meals. The majority of participants consumed tea 2–3 times/day and 2–4 cups (250 mL) daily. The chances of iron deficiency increased with an increasing number of teacups consumed. Lower tea infusion strength in teacups and a duration of tea infusion shorter than 5 min both decreased the chance of iron deficiency.
Our study is the first of its kind to assess tea consumption patterns and its potential impact on iron-related outcomes, specifically among WCA in Kenya. Our results highlight that intensive tea consumption may pose significant health risks for WCA. Strength of our study include a sample size determined based on a sample size calculation; the random sampling method used, a data collection team with extensive knowledge of the local culture and setting; and the large study participation rate. Our study has some weaknesses. As it is a cross-sectional study, no clear causal relationship can be established based on our results. Further, we noticed that students were overrepresented among the participants of our study; therefore, despite our best efforts, results might not be representative to the broader local society of women aged 15–49, as students might represent WCA of different age, education level, and socioeconomic status.
In agreement with our study’s findings, three studies described that tea or coffee is the most preferred beverage in Kenya [4, 11, 27]. The study area (Nandi County) is a tea-growing region harbouring 19 tea factories such as Chebut Tea, Kibwari Tea, and Kipchabo Tea, which could explain the high availability and utilisation of loose tea leaves. The County has hills that normally have very cold weather which could contribute to the high consumption of tea by the locals to keep themselves warm [28]. Similarly, other studies have found that WCA consume tea with meals or within 1 h before or after meals in Kenya [7–9, 11]. When tea is taken less than an hour before or after a meal, a situation is created where phenolic compounds complex with iron in food, subsequently reducing dialysable iron [12].
Our findings demonstrate that the respondents were less associated with iron deficiency when they consumed tea with milk alone as compared to taking milk tea with an accompanying meal. When tea is consumed with milk alone without an accompanying meal, the phenolic compounds in the tea will not have iron to complex with. However, this advantage can be reduced if there is an overlap between the food- and tea-gastric emptying phases [12]. The milk in tea introduces calcium, which is an important inhibitor of iron bioavailability further compounding the iron absorption inhibition. Earlier studies suggested that the dialysability of iron increased when both milk and tea are consumed together [29, 30]. It may imply that calcium availed by milk complex with tannic acid sparing more dialysable iron. On the contrary, more recent studies established that the addition of milk to tea reduced significantly the dialysable iron as compared to when tea or milk is taken alone with meals [31, 32].
A review of determinants of iron bioavailability suggested that an overall increase in the intake of polyphenols attracted an equivalent greater reduction in the dialysable iron [31]. This might be an explanation for the results of this study, as increased tea intake might result in a higher provision of tannic acid in the gut and, as a consequence, reduced bioavailability of iron. While similar studies have reported contrasting results on relationship between tea consumption and iron status [15–17], certain investigations have exclusively focused on iron absorption [12–14]. The results described in our study might be applicable to WCA living in a country or region with high tea/coffee consumption pattern.
Conclusion
Lower tea infusion strength, shorter tea infusion duration, and a lower number of teacups overall consumed decreased the chance of having iron deficiency among WCA in Nandi County, Kenya. A more favourable iron status may be achieved by recommending healthier tea consumption habits to WCA and other risk groups. Further, recommending the consumption of tea 1 h before or after meals instead of consuming it with meals might have further beneficial effects on iron status of WCA.
Acknowledgments
The authors are grateful to the respondents who accepted to participate in the research and to the research assistant team who collected data and blood samples.
Statement of Ethics
This study protocol was reviewed and approved by the Kenyatta University Ethics Review Committee (PKU/2029/11176). Written informed consent was solicited from the respondents before data and blood sample collection. PNN obtained written informed consent from parents/legal guardians for all participants aged under 18 years.
Conflict of Interest Statement
The researchers express no conflicts of interest.
Funding Sources
The study received no funding.
Author Contributions
P.N.N. designed the study, collected data, analysed and interpreted the work, drafted the manuscript, and approved the final version. J.K. and A.W.M. supervised the design of the work, data collection, interpretation of data, and drafting of the manuscript and approved the final version of the paper. D.A.G. and S.L. interpreted the data, revised the manuscript critically for important intellectual content, and approved the final version of the work for publication.
Funding Statement
The study received no funding.
Data Availability Statement
Data used to reach conclusion in this study are not publicly available due to ethical reasons. Further enquiries can be directed to the corresponding author.
Supplementary Material
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Associated Data
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Supplementary Materials
Data Availability Statement
Data used to reach conclusion in this study are not publicly available due to ethical reasons. Further enquiries can be directed to the corresponding author.