
==== Front
Heliyon
Heliyon
Heliyon
2405-8440
Elsevier

S2405-8440(24)12697-7
10.1016/j.heliyon.2024.e36666
e36666
Case Report
Severe iron-deficiency anemia after short-term moderate consumption of green tea in woman: A rare case report
He Yanlang a
Chen Jianyong cjyktz@163.com
b⁎
a Department of Infectious Disease, Shaoyang Central Hospital, Shaoyang, China
b Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
⁎ Corresponding author. cjyktz@163.com
22 8 2024
15 9 2024
22 8 2024
10 17 e3666625 5 2024
20 8 2024
20 8 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
While the mechanisms by which tea consumption hinders iron absorption are well understood, tea-related anemia usually stems from prolonged and excessive intake, which obstructs iron absorption and depletes the body's iron reserves. Consequently, it is uncommon for hemoglobin levels to plummet by 6.9 g/dl solely due to moderate tea consumption over a span of three months. We present a case of severe iron-deficiency anemia in a woman following short-term, moderate green tea consumption. After modifying her tea intake regimen, there was no recurrence of anemia. Clinicians should be mindful that even moderate tea consumption can precipitate severe iron-deficiency anemia in individuals particularly vulnerable to its effects on iron absorption.

Keywords

Iron-deficiency anemia
Short-term moderate consumption
Green tea
Case report
==== Body
pmc1 Introduction

Globally, green tea is widely recognized as a healthful food, celebrated for its various biological activities, including antioxidative, anti-inflammatory, and anti-proliferative properties [1]. Consequently, many nutritionists advocate for its inclusion in a health-promoting lifestyle [2]. However, this does not imply that green tea is entirely devoid of potential adverse effects on human health. Epidemiological surveys reveal that in Kenya's Nandi County, where tea consumption is prevalent, the anemia prevalence rate among women of childbearing age is 86.3 %, with iron deficiency accounting for 45 % of cases [3]. Similarly, a study in West Bengal, India, indicates that 23 % of female tea plantation workers who frequently consume green tea suffer from iron-deficiency anemia(IDA) [4]. These findings suggest the potential ability for green tea to impede iron absorption across different populations and ethnicities. Iron is crucial for the synthesis of hemoglobin, cell growth and differentiation, neurotransmission, immunity, and cardiopulmonary function [[5], [6], [7]]. Iron deficiency can lead to fatigue, poor concentration (brain fog), alopecia, ridged or brittle nails, aching and restless legs, reduced exercise tolerance, anxiety, low mood or depression, and decreased work performance [8]. Therefore, India's National Nutritional Anemia Control Program advises against tea consumption for individuals at risk of anemia [9].

For a long time, researches have generally suggested a connection between excessive tea consumption and iron deficiency. A previous study in Kenya found that iron deficiency was associated with excessive tea consumption (more than three cups per day, extended steeping time (>5 minutes), or strong tea infusion (dark-colored tea)) [3]. Similarly, another study in Japan classified individuals who drank more than three cups of green tea daily as high consumers and linked this to lower serum ferritin levels in postmenopausal women [10]. Fan also reported a case of iron deficiency anemia due to excessive green tea consumption, where the patient drank over 1500ml of green tea almost daily for 20 years [11]. However, for certain individuals with unique physiological constitutions, even moderate tea consumption may pose health risks. This case presents a severe IDA occurring in a woman after short-term, moderate green tea consumption, highlighting the need for increased awareness of the potential adverse effects associated with tea intake.

2 Case report

In August 2023, a 23-year-old female was referred to the Department of Gastroenterology at Jiangxi Provincial People's Hospital for unexplained severe IDA. She had a normal menstrual blood volume of 30–40ml per cycle and reported no family history of blood disorders, chronic intestinal disease, or surgery. She was neither a picky eater nor a vegetarian and consistently followed a balanced diet in line with the recommendations of the Chinese Dietary Guidelines for residents. Her daily intake typically included approximately 500–700g of fresh vegetables, 400–500g of various fruits, and 150–250g of meat products. During her annual physical examination three months prior, no signs of anemia were detected, with her hemoglobin level at 12.0 g/dl (normal range 11.5–15.5 g/dl). Subsequently, she began drinking green tea after learning about its numerous health benefits, consuming two cups daily (about 10–15g of tea with 300–400ml of water). She preferred to drink tea within half an hour after meals, as it helped freshen her breath and alleviate the greasy discomfort from eating—an approach so common among Chinese tea drinkers that it often goes unnoticed.

Aside from experiencing mild dizziness and weakness, she reported no other symptoms such as abdominal pain, dark-colored urine, persistent diarrhea, tarry or bloody stools, or recent weight loss. The physical examination revealed pallor of the lips and nail beds, without evidence of cheilosis. Laboratory data (Table 1) indicated anemia with thrombocytosis, showing hemoglobin (Hb) levels at 5.1 g/dl (normal range 11.5–15.5 g/dl), mean corpuscular volume (MCV) at 68.3 fl (normal range 80–100 fl), mean corpuscular hemoglobin (MCH) at 19.3 pg (normal range 26–32 pg), mean corpuscular hemoglobin concentration (MCHC) at 283 g/L (normal range 320–360 g/L), serum ferritin at 2.5 ng/ml (normal range 13–150 ng/ml), transferrin saturation at 10 % (normal range 20–50 %), and platelet count at 507*10⁹/L (normal range 100–300*10⁹/L). Based on the latest Chinese guidelines [12], she was diagnosed with severe IDA. Biochemical studies did not reveal any hepatic, renal, or thyroid dysfunction. Urinalysis also did not detect microhematuria or pyuria. Tumor marker levels were within the normal range, and hemoglobin electrophoresis did not show a beta thalassemia pattern. Routine rheumatic antibody tests were negative, partially ruling out immune-related hemolysis. Despite a negative fecal occult blood test, we proceeded with comprehensive gastrointestinal endoscopy and abdominal imaging to exclude any potential organic diseases. Esophagogastroduodenoscopy, colonoscopy, enteroscopy, and computerized tomography of the abdomen revealed no abnormalities or bleeding points, so a mucosal tissue biopsy of the digestive tract was not performed. A gynecological consultation, including a routine examination, hormone testing, and pelvic ultrasound, ruled out gynecological tumors or hormone-related bleeding. Bone marrow examination (Fig. 1) revealed active erythroid cell proliferation, predominantly late erythroblasts with cytoplasmic deficiency and poor hemoglobin formation. Iron staining was negative both intracellularly and extracellularly, with no other abnormalities observed, confirming a diagnosis of simple IDA.Table 1 Changes in anemia-related indicators in the patient.

Table 1	On hospital day 1	On hospital day 2	On hospital day 3	On hospital day 6	On hospital day 9	On hospital day 12	On hospital day 15
On discharge	1 month after discharge	3 months after discharge	6 months after discharge	
hemoglobin	5.1	7.6	9.8	9.2	9.1	9.7	10.2	8.1	12.0	12.5	
mean corpuscular volume	68.3	75.2	79.8	78.0	77.2	78.7	81.0	76.8	90.2	92.3	
mean corpuscular hemoglobin	19.3	22.9	24.9	24.3	24.3	24.8	25.5	24.3	28.8	29.9	
mean corpuscular hemoglobin concentration	283	293	312	300	298	315	322	305	340	347	
serum ferritin	10	NA	25	NA	NA	42	50	43	70.3	95.4	
main treatment	oral iron supplement	the first transfusion	the second transfusion	oral iron supplement	stop drinking green tea	No change	No change	oral iron supplement
no more than 5g/day of tea
1-h time interval	No change	No change	
oral iron supplement	oral iron supplement	oral iron supplement	

Fig. 1 Result of the patient' s bone marrow examinatio

Fig. 1 The bone marrow examination revealed active proliferation of erythroid cells, mainly late erythroblasts with lack of cytoplasm and poor formation of hemoglobin. Negative manifestation of iron staining was also observed both intracellularly and extracellularly.

Fig. 1

Due to her severe IDA, she was prescribed oral slow-release ferrous sulfate 300 mg three times daily for iron supplementation, and an emergency blood transfusion was arranged. When her hemoglobin level increased to 9.0 g/dl, in accordance with the latest Chinese blood transfusion guidelines, we discontinued the transfusion but continued the oral slow-release ferrous sulfate. However, following the cessation of the transfusion, her hemoglobin levels began to gradually decline (Table 1). This unexpected development left us perplexed, as the underlying cause of her IDA remained unidentified.

We then turned our attention to her history of green tea consumption. Despite her moderate intake, considering individual variations, we advised her to stop drinking green tea. Subsequently, her hemoglobin and serum iron levels began to gradually increase again (Table 1), reaching 10.2 g/dl at discharge. After discharge, she continued oral iron supplementation but was reluctant to give up her green tea habit, believing that reducing consumption frequency would not significantly impact her IDA. However, at a follow-up one month later, her hemoglobin had dropped to 8.1 g/dl. Referring to a safety review on green tea [13], we advised her to limit her intake to no more than 5 g of green tea leaves per day to satisfy her preference. Based on a previous clinical trial [14], we also recommended a one-hour interval between meals and green tea consumption to minimize the inhibition of iron absorption. The patient agreed to this regimen and adhered to it over the following months. At follow-ups 3 and 6 months after discharge, following our recommended tea-drinking regimen, her hemoglobin levels increased to 12.0 g/dl and 12.5 g/dl, respectively, with serum ferritin levels at 70.3 ng/ml and 95.4 ng/ml. Currently, she reports no discomfort during follow-up. At our outpatient department, she continues to undergo routine blood examinations without any recurrence of anemia.

3 Discussion

To our knowledge, this is the first detailed case report of severe iron deficiency anemia (IDA) in a woman following short-term moderate green tea consumption, underscoring the individual variability in how tea consumption impacts IDA. After resuming green tea intake post-discharge, her IDA recurred. However, by adjusting the quantity and timing of green tea consumption, her IDA was concurrently resolved. These findings strongly suggest that even short-term moderate green tea consumption may lead to severe IDA, a concern that has previously been underappreciated by clinicians. This case report offers novel insights into the diagnosis of tea-related anemia.

The form of iron in food is either heme or nonheme. Polyphenols, phytate, and calcium in green tea can inhibit nonheme iron absorption by chelating iron and affecting intestinal iron transporters[15,16]. Among these inhibitors, tannins containing a trihydroxy-benzene group (galloyl) are extensively studied. They can reduce nonheme iron absorption by forming insoluble mineral complexes with Fe3+ [17], and this effect is further amplified in the presence of phytates. Studies have shown that in soybean meal containing tannins/polyphenols, high-phytate soybean meal significantly reduces the bioavailability of dietary iron compared to low-phytate soybean meal [18]. This is likely due to phytates'ability to chelate cations and form insoluble complexes with iron in the upper digestive tract. Since humans lack intestinal phytase, phytates cannot be digested or absorbed, leading to a dose-dependent reduction in iron absorption [19,20]. More importantly, the Chinese diet is rich in phytates, with a median intake of 1186 mg [21], higher than in Western developed countries. This suggests that tea drinkers in China may be at an increased risk of iron deficiency.

Furthermore, although the absorption of heme iron is relatively less affected by diet, it is not negligible. Studies suggest that the uptake of heme iron occurs via receptor-mediated endocytosis, where heme is internalized into endosomes and then degraded by heme oxygenases (HOs) to release free ferrous iron, which is likely transported to the cytoplasm by divalent metal transporter 1 (DMT1) [22]. Subsequently, heme-derived free iron in enterocytes joins the labile iron pool, ready to be incorporated into ferritin (Ft) for temporary storage or exported across the basolateral membrane via ferroportin-1 (FPN-1) into circulation [23]. Polyphenols can significantly inhibit the absorption of heme iron in the intestines by reducing basolateral iron export in Caco-2 cells. Even at very low concentrations (0.46 mg/L), (−)-epigallocatechin-3-gallate (EGCG), grape seed extract (GSE), and green tea extract (GT) significantly reduced heme iron transport across the cell monolayer during a 7-h transport assay. According to IC50 values, transepithelial heme iron transport across the cell monolayer can be reduced by 50 % with 3.6, 3.0, and 5.1 mg/L of EGCG, GSE, and GT, respectively [24]. Polyphenols have a dose-dependent inhibitory effect on heme iron absorption [24], which may partially explain why patients in previous case reports typically developed IDA only after prolonged excessive tea consumption [25,26]. However, the expression of other proteins involved in iron metabolism and basolateral iron transport did not show significant changes [24], and the specific mechanisms by which polyphenols regulate heme iron remain unclear. Additionally, calcium in tea can influence heme iron absorption by modulating enterocyte iron transporter proteins, which may occur during the initial entry of iron into the mucosal cell via inhibition of iron transport [27]. A randomized clinical trial on children consuming iron-fortified milk showed that reduced calcium content led to a 18–27 % increase in heme iron absorption [28]. Given that green tea is rich in these substances, long-term excessive consumption may lead to IDA.

Our case challenges the conventional view of tea-related anemia held by clinicians. Although existing mechanisms and Chinese guidelines clearly indicate that tea can contribute to IDA, literature has not documented instances of moderate tea consumption leading to severe IDA in the short term. This may be attributed to adequate dietary iron intake and the body's own iron reserves. A Danish study revealed that daily dietary iron intake and bioavailability were sufficient to maintain optimal iron status in 80-year-old subjects, with some even experiencing mild iron overload [29]. Other studies have indicated that the human body contains 3–4 g of iron, with the total erythroid mass holding 30 mg of iron per kilogram of body weight, while most of the remaining iron is stored in the liver [30]. The body absorbs only 1–2 mg of iron per day from the gut, and its iron stores can sustain iron consumption for a period of time, even in the absence of dietary iron intake.

Thus, current guidelines do not emphasize the risk of moderate tea consumption in relation to IDA. Although the latest British guidelines recognize tea consumption as a risk factor for IDA, they do not impose limits on normal tea intake [31]. Similarly, Australian guidelines identify tea as a potential cause of inadequate response to oral iron therapy but do not include it in their clinical pathways [32]. In Eastern countries like China, the most recent guidelines also mention the risk of IDA associated with strong tea consumption rather than moderate tea intake (Table 2). Therefore, even if we had been aware of the patient's history of tea drinking prior to treatment, we did not focus on or consider this factor. Our case is rare and suggests that tea consumption, regardless of quantity or duration, may be an important etiology to consider in severe IDA for certain individuals.Table 2 Common causes of absolute iron deficiency in latest Chinese guideline.

Table 2Etiology	Mechanism	
Insufficient iron intake	
Diet	Such as long-term vegetarian, low iron content in the diet; Or drink strong coffee or strong tea to inhibit iron absorption	
Absence of stomach acid	For example, atrophic gastritis, the use of antacids or proton pump inhibitors, Helicobacter pylori infection, and bariatric surgery lead to insufficient gastric acid and affect iron absorption	
Small Intestinal mucosal diseases	Reduce iron absorption	
Chronic diarrhea, celiac disease, etc	Reduce iron absorption	
Hepcidin was increased	For example, TMPRSS6 gene mutation can increase hepcidin level and inhibit iron absorption. Obesity	
Increased iron demand	
Children and adolescents	Growth develops rapidly, and the iron demand increases	
Women during pregnancy	Iron demand increases during pregnancy	
Women during their period	Losing iron through menstruation, the iron demand increases	
EPO treatment period	Erythropoiesis and iron requirements	
Blood loss	
Blood loss from the digestive system	Esophageal blood loss: varicose veins, esophageal cancer, ulcer, reflux esophagitis, etc. (2) Gastric blood loss: gastric cancer, gastric polyps, gastric ulcer, gastric bleeding and gastric angiectasis caused by the use of aspirin and other non-steroidal anti-inflammatory drugs; (3) Small intestinal blood loss: duodenal ulcer, inflammatory bowel disease, parasites (hookworm, etc.), lymphoma, tumors and polyps, telangiectasia, diverticulum, etc. (4) Colonic blood loss: colon cancer, polyps, diverticular bleeding, inflammatory bowel disease, type 2 von Willebrand disease, angiodysplasia, etc. (5) Anal blood loss: hemorrhoids bleeding	
Gynecological blood loss	Excessive menstrual bleeding caused by uterine fibroids, adenomyosis, gynecological malignant tumors, bleeding diseases (such as von Willebrand disease, hemophilia carriers, abnormal platelet count and function, etc.), intrauterine device, etc	
Blood loss from the urinary system	tumor diseases such as kidney cancer or bladder cancer; Infectious diseases such as schistosomiasis, viral infections, tuberculosis; Urinary calculi: such as kidney stones, bladder stones, causing hematuria; Intravascular hemolysis (e.g., PNH, mechanical heart valves, malaria, etc.) results in destruction of red cells	
Blood loss from the respiratory system	Lung tumor, infection (lung abscess, fungal infection, tuberculosis infection, etc.) cause hemoptysis	
Donation of blood	Frequent blood donation	
Iatrogenic blood loss	Frequent hemodialysis	
Comprehensive factor	
Exercise (rare)	Reduced dietary iron intake; occasional hemolysis	
TMPRSS6 is a transmembrane serine protease 6. EPO is erythropoietin; PNH is paroxysmal nocturnal hemoglobinuria.

We do not advocate for dismissing the value of tea consumption among the general public. Currently, epidemiological studies lack definitive evidence necessitating restrictions on tea consumption among healthy individuals to prevent iron deficiency [33,34]. Moreover, studies examining the correlation between tea intake levels and serum ferritin levels have yielded inconsistent results [35,36]. Our case study suggests that individuals who are interested in tea consumption, even those with factors influencing iron metabolism, may consider adjusting the amount and timing of their tea consumption as a viable option.

Currently, there is no universally recommended daily intake for green tea. Some studies have identified a link between green tea extract (GTE) or epigallocatechin gallate (EGCG) and liver injury [37,38]. Thus, safety assessments have predominantly focused on establishing safe thresholds for GTE and EGCG intake to prevent hepatic damage [[39], [40], [41]], often overlooking the potential impact on iron absorption associated with green tea consumption. Consequently, data in this area remain limited. Given the inconsistent chemical composition of GTE across various studies, we attempted to regulate the patient's green tea intake based on EGCG levels. Table 3 presents data from studies on human hepatic toxicity related to EGCG. A comprehensive safety review set the safe threshold for EGCG intake in beverage form at 704 mg/day [13]. Another European review suggested a threshold of 800 mg/day for high-level consumers [41], while Japanese researchers reported no observed hepatotoxicity with EGCG intake below 600 mg/person/day in clinical intervention studies [40]. According to data from the United States Department of Agriculture Flavonoid Database, approximately 70 mg of EGCG is found per gram of green tea leaves. Considering the patient's susceptibility, we recommended limiting her daily green tea consumption to no more than 5 g. The patient strictly adhered to this advice, and during follow-ups, she did not experience a recurrence of IDA or hepatotoxicity. Therefore, our case may offer valuable intake guidelines for similar patients.Table 3 Data from various human safety studies on EGCG intake.

Table 3Authors	EGCG intake per day	Subject of study	Duration	Findings related to the liver and severity rating	Reference	
Tsuchida et al., 2002	114.9 mg	39 healthy subjects; 20M of 30–62 years (mean 42.2) and 19 menopausal women	12wks	No adverse effects on liver	T. Tsuchida et al. Reduction of body fat in humans by long-term ingestion of catechins. Prog. Med., 22 (2002), pp. 2189-2203	
Matsuyama et al., 2008	102.3 mg	19 overweight children (14M/5F)	6m	No adverse effects on liver	T. Matsuyama et al. Catechin safely improved higher levels of fatness, blood pressure, and cholesterol in children.
Obesity (Silver Spring), 16 (2008), pp. 1338-1348	
Yoneda et al., 2009	114.9 mg	77 healthy males	11–17m	No adverse effects on liver	T. Yoneda et al. Effectiveness and safety of 1-year ad libitum consumption of a high-catechin beverage under nutritional guidance. Metab. Syndrome Relat. Disord., 7 (2009), pp. 349-356	
Ullmann et al., 2004	800 mg (highest dose)	27 healthy males	10d	One subject of the 800 mg group presented with a slight and reversible increase of ALT	U. Ullmann et al. Plasma-kinetic characteristics of purified and isolated green tea catechin epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy volunteers. Int. J. Vitam. Nutr. Res., 74 (2004), pp. 269-278	
Widlansky et al., 2007	300mg	21 subjects (15M/6F) with coronary artery disease	2wks	No adverse effects on liver	M.E. Widlansky et al. Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease.
J. Am. Coll. Nutr., 26 (2007), pp. 95-102	
Yoshikawa et al., 2012	810 mg	20 healthy subjects (8M/12F)	1wk	No adverse eﬀects on liver	T. Yoshikawa et al. Effects of short-term consumption of a large amount of tea catechins on chromosomal damage, oxidative stress markers, serum lipid, folic acid, and total homocysteine levels: a randomized, double-blind, controlled study.
Jpn. J. Clin. Pharmacol. Therapeut., 43 (2012), pp. 9-16	
Laurie et al., 2005	676mg	16 subjects (8M/8F) with lung cancer	4wks	No adverse effects on liver	S.A. Laurie et al. Phase I study of green tea extract in patients with advanced lung cancer. Canc. Chemother. Pharmacol., 55 (2005), pp. 33-38	
Brown et al., 2011	424–753 mg	63 healthy males	6wks	No adverse effects on liver	A.L. Brown et al. Health effects of green tea catechins in overweight and obese men: a randomised controlled cross-over trial. Br. J. Nutr., 106 (2011), pp. 1880–1889	
Tsao et al., 2009	277 mg, 416 mg, 554 mg	30 subjects (13M/17F) with high-risk of oral premalignant lesions	12wks	No adverse effects on liver	A.S. Tsao et al.Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions.Cancer Prev. Res. (Phila), 2 (2009), pp. 931-941	
Chen et al., 2016	856.8 mg	39 obese females	12wks	No adverse effects on liver	I.J. Chen et al. Therapeutic effect of high-dose green tea extract on weight reduction: a randomized, double-blind, placebo-controlled clinical trial. Clin. Nutr., 35 (2016), pp. 592-599	
Chantre and Lairon, 2002	1080 mg	70 overweight to obese subjects (7M/63F)	12wks	1 subject with an increase in transaminase	P. Chantre, D. Lairon. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity.
Phytomedicine, 9 (2002), pp. 3-8	
Pezeshki et al., 2016	157 mg	35 subjects (16M/19F) with nonalcoholic fatty liver disease	90d	No adverse effects on liver	A. Pezeshki et al.The effect of Green tea extract supplementation on liver enzymes in patients with nonalcoholic fatty liver disease.
Int. J. Prev. Med., 7 (2016), p. 28	
Roshdy et al., 2013	360 mg	22 females with symptomatic uterine fibroids	4m	No adverse effects on liver	E. Roshdy et al. Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study.
Int. J. Womens Health, 5 (2013), pp. 477-486	
Hsu et al., 2011a	856.8 mg	35 overweight or obese subjects (12M/23F)	16wks	No adverse effects on liver	C.H. Hsu et al.
Does supplementation with green tea extract improve insulin resistance in obese type 2 diabetics? A randomized, double-blind, and placebo-controlled clinical trial
Alternative Med. Rev., 16 (2011), pp. 157-163	
Fukuzawa et al., 2014	395 mg	26 subjects (13M/13F) with nonalcoholic steatohepatitis	6m	No adverse effects on liver	Y. Fukuzawa et al.
Effects of green tea catechins on nonalxoholic steatohepatitis (NASH) patients
J. Funct. Foods, 9 (2014), pp. 48-59	
Qian et al., 2012	232 mg	76 females with osteopenia	6m	No adverse effects on liver	G. Qian et al. Mitigation of oxidative damage by green tea polyphenols and Tai Chi exercise in postmenopausal women with osteopenia. PLoS One, 7 (2012) e48090	
de la Torre et al., 2016	800 mg (highest dose)	43 subjects (24M/19F) with Down's Syndrome	12m	No adverse effects on liver	R. de la Torre et al. Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol., 15 (2016), pp. 801-810	
Dostal et al., 2015	843 mg	538 post-menopausal females at risk for breast cancer	1y	53 incidences of ALT elevations in treatment group:	A.M. Dostal et al. The safety of green tea extract supplementation in postmenopausal women at risk for breast cancer: results of the Minnesota Green Tea Trial. Food Chem. Toxicol., 83 (2015), pp. 26-35	
Nguyen et al., 2012	800 mg	24 male subjects with prostate cancer	3–6wks	1 subject with Grade 1 ALT elevation (4 %)	M.M. Nguyen et al.
Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: evaluation of potential chemopreventive activities
Cancer Prev. Res. (Phila), 5 (2012), pp. 290-298	
McLarty et al., 2009	800 mg	26 males with prostate cancer	12-214d,	No adverse effects on liver	J. McLarty et al.Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev. Res. (Phila), 2 (2009), pp. 673-682	
Dryden et al., 2013	400 or 800 mg	13 subjects (6M/7F) with mild to moderate	8wks	No adverse effect on liver	G.W. Dryden et al. A pilot study to evaluation the safety and efficacy of an oral dose of (−) epigallocatechin-3-gallate-rich polyphenon E in patients with mild to moderate ulcerative colitis.
Inflamm. Bowel Dis., 19 (2013), pp. 1904–1912	
Wu et al., 2012	800 mg	71 overweight or obese females	2m	No adverse effects on liver	A.H. Wu et al. Effect of 2-month controlled green tea intervention on lipoprotein cholesterol, glucose, and hormone levels in healthy postmenopausal women. Cancer Prev. Res. (Phila), 5 (2012), pp. 393-402	
Ahn et al., 2003	200 mg	14 females with cervical lesions	12wks	One subject with abnormal liver function at week 4 that returned to normal for week 8 and 12	W.S. Ahn et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions.
Eur. J. Canc. Prev. Official J. European Canc. Prevent. Org., 12 (2003), pp. 383-390	
Garcia et al., 2014	800 mg	41 females with persistent high risk HPV	4m	4 subjects had elevated AST	F.A. Garcia et al. Results of a phase II randomized, double-blind, placebo-controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia. Gynecol. Oncol., 132 (2014), pp. 377-382	
Shanafelt et al., 2009	800–4000 mg	33 subjects (24M/9F) with chronic	Up to 6m	33 % of subjects, all with Grade 1	T.D. Shanafelt et al. Phase I trial of daily oral Polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leukemia. J. Clin. Oncol., 27 (2009), pp. 3808-3814	
Shanafelt et al., 2013	2000 mg for 7 days, then increased to 4000 mg	42 subjects (30 M/11 F) with chronic lymphocytic leukemia	6m	13 subjects with Grade 1, 6 subjects with Grade 2 and 1 subject with Grade 3 transaminitis	T.D. Shanafelt et al. Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia.Cancer, 119 (2013), pp. 363-370	
Lovera et al., 2015	800 mg	10 subjects (9 F/1 M) with multiple sclerosis	6m	One subject with Grade 1	J. Lovera et al. Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: phase I single group and phase II randomized placebo-controlled studies.
J. Neurol. Sci., 358 (2015), pp. 46-52	
Joe et al., 2015	1200 mg	33 subjects (10F/23M) with Barrett's	6m	Study discontinued due to	A.K. Joe et al. Phase Ib randomized, double-blinded, placebo-controlled, dose escalation study of polyphenon E in patients with Barrett's esophagus. Cancer Prev. Res. (Phila), 8 (2015), pp. 1131-1137	
Crew et al., 2012	1600 mg	30 females with breast cancer	6m	2 subjects with Grade 1 transaminitis and 1 subject with Grade 3 elevated ALT; 2 subject with Grade 1 high alkaline phosphatase	K.D. Crew et al. Phase IB randomized, double-blinded, placebo-controlled, dose escalation study of polyphenon E in women with hormone receptor-negative breast cancer.
Cancer Prev. Res. (Phila), 5 (2012), pp. 1144-1154	
Kumar et al., 2015	400 mg	36 males	1y	Liver function was monitored but data not reported	N.B. Kumar et al. Randomized, placebo-controlled trial of Green tea catechins for prostate cancer prevention.
Cancer Prev. Res. (Phila), 8 (2015), pp. 879-887	
Lovera et al., 2015	800 mg	7 subjects (5F/2M) with multiple sclerosis	1y	4 subjects had Grade 1 abnormal liver enzymes, 1subject had Grade 4 abnormal liver function	J. Lovera et al. Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: phase I single group and phase II randomized placebo-controlled studies.
J. Neurol. Sci., 358 (2015), pp. 46-52	
Ahn et al., 2003	200 mg	10 females with cervical lesions	12wks	No adverse effects on liver	W.S. Ahn et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions.
Eur. J. Canc. Prev. Official J. European Canc. Prevent. Org., 12 (2003), pp. 383-390	
Mielgo-Ayuso et al.,	300 mg	43 obese females	12wks	No adverse effects on liver	J. Mielgo-Ayuso et al. Effects of dietary supplementation with epigallocatechin-3-gallate on weight loss, energy homeostasis, cardiometabolic risk factors and liver function in obese women: randomised, double-blind, placebo-controlled clinical trial.
Br. J. Nutr., 111 (2014), pp. 1263-1271	
Hill et al., 2007	300 mg	19 postmenopausal overweight or obese females	12wks	No adverse effects on liver	A. M. Hill et al. Can EGCG reduce abdominal fat in obese subjects? J. Am. Coll. Nutr., 26 (2007), pp. 396S-402S	
de la Torre et al., 2014	200 or 400 mg	13 subjects (6F/7M) with Down's Syndrome	3m	No adverse effects on liver	R. de la Torre et al. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol. Nutr. Food Res., 58 (2014), pp. 278-288	
Panza et al., 2008	233.4mg	14 healthy males	7d	No adverse effects on liver	V.S. Panza et al. Consumption of green tea favorably affects oxidative stress markers in weight-trained men. Nutrition, 24 (2008), pp. 433-442	
Kim et al., 2006	256 mg	20 Korean males who were chronic smokers	2wks	No adverse effects on liver	W. Kim et al.Effect of green tea consumption on endothelial function and circulating endothelial progenitor cells in chronic smokers. Circ. J., 70 (2006), pp. 1052-1057	
Toolsee et al., 2013	704 mg	65 subjects (33M/32F) at risk for diabetes	14d	No adverse effects on liver	N.A. Toolsee et al.Effectiveness of green tea in a randomized human cohort: relevance to diabetes and its complications
BioMed Res. Int., 2013 (2013), p. 412379	
Henning et al., 2015	562 mg	34 males with prostate cancer	3–8wks	No adverse effects on liver	S.M. Henning et al.Randomized clinical trial of brewed green and black tea in men with prostate cancer prior to prostatectomy
Prostate, 75 (2015), pp. 550-559	
Yang et al., 2012	NR	15 overweight subjects (8M/7F)	6wks	No adverse effects on liver	H.Y. Yang et al.Beneficial effects of catechin-rich green tea and inulin on the body composition of overweight adults
Br. J. Nutr., 107 (2012), pp. 749-754	
Basu et al., 2010	440 mg	13 obese subjects (10F/3M) with metabolic syndrome	8wks	No adverse effects on liver	A. Basu et al. Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. J. Am. Coll. Nutr., 29 (2010), pp. 31-40	
Maki et al., 2009	214.4 mg	65 obese subjects (32M/33F)	12 wks	No adverse effects on liver	K.C. Maki et al. Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. J. Nutr., 139 (2009), pp. 264-270	
Nagao et al., 2005	135 mg	17 healthy males	12 wks	No adverse effects on liver	T. Nagao et al. Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men.
Am. J. Clin. Nutr., 81 (2005), pp. 122-129	
Nagao et al., 2007	100.3 mg	123 Japanese subjects (51F/72M) withvisceral fat type obesity	12 wks	No adverse effects on liver	T. Nagao et al. A green tea extract high in catechins reduces body fat and cardiovascular risks in humans Obesity, 15 (2007), pp. 1473-1483	
Nagao et al., 2009	100.3 mg	23 overweight or obese Japanese subjects(15F/8M) with type 2 diabetes	12 wks	No adverse effects on liver	T. Nagao et al.A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes
Obesity (Silver Spring), 17 (2009), pp. 310-317	
F = female, M = male, wk = week, d = day, m = month. y = year.

NR = not reported, F = female, M = male, wk = week, d = day, m = month, y = year.

Furthermore, the interval between tea consumption and meals is also an important factor to consider. Research indicates that habitual tea drinking during meals may significantly increase the risk of chronic iron depletion [42,43]. In a study among anemic women in Kenya, Lohner et al. [3] found that most respondents (71.7 %) consumed tea during breakfast, slightly over half (53.4 %) during lunch, and over one-third (37.7 %) at supper. Those who did not drink tea with meals typically consumed it 1 h before or less than 1 h after eating. Tijburg et al. [44] also suggest that tea should be consumed between meals rather than during them. These findings suggest that it is preferable to drink tea at a certain interval from meals to minimize its impact on iron absorption. However, there are currently no professional guidelines that clearly define the optimal timing for tea consumption to minimize its impact on iron absorption. We referenced a randomized controlled study that reported a 37 % increase in iron absorption when tea was consumed 1 h after meals compared to drinking it with meals. The inhibitory effect of tea on iron absorption decreased from 37.2 % to 18.1 % when tea was consumed 1 h after meals, rather than with water [14]. Additionally, Disler et al. [45]. found that drinking tea 3 h after meals also reduced its inhibitory effect on iron absorption from iron-rich meals, though not significantly different from the one-hour interval. Considering the typical midday rest and afternoon work pattern in Chinese life, we recommended the patient drink tea 1 h after meals. The absence of recurrent IDA in follow-ups supports the effectiveness of this approach.

Some limitations remain in this report. First, due to the specificity of this case report, we were unable to elucidate the precise mechanism by which short-term moderate tea consumption caused severe IDA. Therefore, the conclusions drawn still require confirmation through further studies. Second, as the findings from endoscopy were unremarkable, we did not perform a biopsy of the digestive tract mucosa, which may have limited our ability to detect any underlying malabsorptive disorders. Consequently, our findings should be interpreted with caution.

4 Conclusion

Our case underscores that even short-term moderate consumption of green tea can result in severe IDA. In situations where routine tests fail to identify the cause of IDA or when iron supplementation proves ineffective, clinicians should remain vigilant and thoroughly examine patients’ lifestyle habits, such as tea consumption, even if they seem normal. For patients unwilling to completely abstain from tea, adjusting the quantity and timing of tea intake may be a feasible approach.

Ethical approval

Since this study belonged to a single case report, the data were anonymous, and had no identifiable information about the patient, the need for ethics approval was waived by Ethics Committee of the Jiangxi Provincial People's Hospital.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Funding

This work was supported by 10.13039/100014717 National Natural Science Foundation of China (No. 81960111 ).

Data availability statement

The original contributions presented in the study have been included in the article. According to the requirements of the patient, further data will be made available from the corresponding author on reasonable request.

CRediT authorship contribution statement

Yanlang He: Writing – original draft. Jianyong Chen: Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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