Severe iron-deficiency anemia after short-term moderate consumption of green tea in woman: A rare 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 Changes in anemia-related indicators in the patient. 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. 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.

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

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

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.

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

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.

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 2 Etiology 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. Common causes of absolute iron deficiency in latest Chinese guideline. 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 3 Authors 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. Data from various human safety studies on EGCG intake. 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.

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.

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.

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.