Green tea contraindicated in pregnancy
April 2, 2005
Subject: The mechanism by which green tea protects against cancer by blocking folic acid metabolism makes it potentially dangerous during pregnancy.
The human mind is designed to make order out of chaos, to take diverse sensory input and turn it into sight, vision and touch. These sensory inputs are integrated into experience. Experience generates thought and our minds continually want to order and explain that experience into simple equations. At least that is how I'm rationalizing things today.
People often want simple clear cut answers in life. In terms of health they want to know, “Is this good for me or bad for me.” Life is rarely black and white and rarely are there answers as simple as people would like them.
In regard to health, there are few things which are always “good for you.” Instead things may be beneficial in certain situations and certain times. At other times they may be harmful. It's all a matter of time and place. This appears to be the story with green tea.
What has caused these ramblings is a recent article published in Cancer Research on green tea. Roger Thorneley from the United Kingdom and his colleagues in Spain have published an explanation why green tea drinkers have lower incidences of gastric and esophageal cancers.
The benefits of green tea are generally attributed to a chemical called epigallocatechin gallate (EGCG).
Why does EGCG prevent cancer? It seems that EGCG blocks the enzyme dihydrofolate reductase, an enzyme essential for tumor cell growth. [i] Without this enzyme, folic acid is unavailable in the cells. Folic acid is needed for cells to divide. Without folic acid cell division is slowed down. This is how the chemotherapy drug methotrexate works, blocking folic acid, although of course EGCG has fewer side effects.
The good news is that EGCG blocks folic acid metabolism preventing tumor growth. This is also the bad news. Other cells besides tumor cells need folic acid to divide.
It is well proven that low folic acid levels increase the risk for a mother to give birth to a child with spina bifida. A study published in 2,000 established a worrisome link between tea consumption and spina bifida. Women who drank more than three cups of tea a day were almost three times as likely to give birth to a child with spina bifida as non tea drinkers. [ii] Thorneley's study explains the mechanism causing this increase and suddenly gives more weight to these earlier observations.
This information should certainly give us pause and then produce a great many questions, most of which I can't answer.
Green tea should certainly be avoided during pregnancy and for several months prior to conception. That much is clear.
Low folic acid levels are associated with elevated homocysteine levels. High homocysteine increases the risk of heart disease and other undesirable conditions. Does tea drinking lower the folate enough to raise homocysteine levels? A 2003 study that looked at black tea consumption and homocysteine levels found no effect [iii] but an earlier 2001 study on coffee and black tea did see an effect. [iv] None of these studies looked at green tea and homocysteine. Could the effect be large enough to be clinically significant? That is, is it enough to increase heart disease in green tea drinkers? We don't know.
Folic acid deficiency causes hematological and neurological damage similar to vitamin B-12 deficiency. Should people drinking large quantities of green tea or taking large doses of green tea extract be concerned about folic acid deficiency? We don't know.
When methotrexate is used to treat certain illnesses, such as psoriasis, supplementing with folate decreases the drug side effects without decreasing therapeutic benefit. Should we supplement with folate when using green tea? We don't know.
Methotrexate is frequently prescribed to treat rheumatoid arthritis and psoriasis. Could green tea benefit people with either of these conditions? Once again we don't know.
I would have liked green tea to be a “good guy” in that I could tell everyone to drink it because it was “healthy.” Well it doesn't look like it will be that simple. There are more questions than answers at this point.
Here's one last little thought. A chemical very similar to the epigallocatechin gallate (EGCG) in green tea is found in chocolate. Are we going to have to say that chocolate should be avoided during pregnancy?
I don't think any of us really want to hear the answer to that question.
[i] Cancer Res. 2005 Mar 15;65(6):2059-64
The antifolate activity of tea catechins.
Navarro-Peran E, Cabezas-Herrera J, Garcia-Canovas F, Durrant MC, Thorneley RN, Rodriguez-Lopez JN.
Grupo de Investigacion de Enzimologia, Departamento de Bioquimica y Biologia Molecular A, Facultad de Biologia, Universidad de Murcia , Spain .
A naturally occurring gallated polyphenol isolated from green tea leaves, (-)-epigallocatechin gallate (EGCG), has been shown to be an inhibitor of dihydrofolate reductase (DHFR) activity in vitro at concentrations found in the serum and tissues of green tea drinkers (0.1-1.0 micromol/L). These data provide the first evidence that the prophylactic effect of green tea drinking on certain forms of cancer, suggested by epidemiologic studies, is due to the inhibition of DHFR by EGCG and could also explain why tea extracts have been traditionally used in "alternative medicine" as anticarcinogenic/antibiotic agents or in the treatment of conditions such as psoriasis. EGCG exhibited kinetics characteristic of a slow, tight-binding inhibitor of 7,8-dihydrofolate reduction with bovine liver DHFR (K(I) = 0.109 micromol/L), but of a classic, reversible, competitive inhibitor with chicken liver DHFR (K(I) = 10.3 micromol/L). Structural modeling showed that EGCG can bind to human DHFR at the same site and in a similar orientation to that observed for some structurally characterized DHFR inhibitor complexes. The responses of lymphoma cells to EGCG and known antifolates were similar, that is, a dose-dependent inhibition of cell growth (IC50 = 20 micromol/L for EGCG), G0-G1 phase arrest of the cell cycle, and induction of apoptosis. Folate depletion increased the sensitivity of these cell lines to antifolates and EGCG. These effects were attenuated by growing the cells in a medium containing hypoxanthine-thymidine, consistent with DHFR being the site of action for EGCG.
PMID: 15781612 [PubMed - in process]
[ii] Ann Epidemiol. 2000 Oct 1;10(7):476-477.
Prenatal tea consumption and risks of anencephaly and spina bifida.
Correa A, Stolley A, Liu Y.
National Center for Environmental Health, Centers for Disease Control, Atlanta , GA , USA
PURPOSE: To evaluate the relationship between prenatal tea consumption and risk of anencephaly and spina bifida.METHODS: Data from the population-based Atlanta Birth Defects Case-Control Study were examined. Cases were infants with anencephaly (n = 122) or spina bifida (r = 154) and no other associated anomalies, and identified between 1968 and 1980. Controls were infants without birth defects (n = 3029) identified from birth certificates of the same birth cohort and frequency matched to cases by race, period of birth, and hospital of birth.RESULTS: Maternal tea consumption during the periconceptional period (3 months before through the first trimester of pregnancy) was reported at 82, 83.6, and 92.9% among controls, anencephaly, and spina bifida cases, respectively. With subjects whose mothers consumed no tea as a reference, odds ratios (OR) for tea consumption during the periconceptional period (adjusted for gender, race, period of birth, maternal age, education, alcohol consumption, smoking, and periconceptional multivitamins) were: anencephaly 0.9 (95% confidence limits (CI) 0.5-1.5); spina bifida 2.3 (CI 1.2-4.4). Odds ratios for spina bifida and number of cups of tea consumed/day were: 1-2 cups 2.1 (CI 1.1-4.0); 3+ cups 2.8 (CI 1.4-5.6). Consumption of other caffeinated beverages was not associated with risk for anencephaly or spina bifida.CONCLUSIONS: Further studies are warranted to corroborate and elucidate the observed association between tea consumption and spina bifida.
PMID: 11018418 [PubMed - as supplied by publisher]
[iii] Am J Clin Nutr. 2003 Apr;77(4):907-11.
Can black tea influence plasma total homocysteine concentrations?
Hodgson JM, Burke V, Beilin LJ, Croft KD, Puddey IB.
School of Medicine & Pharmacology, University of Western Australia, and the Western Australian Institute for Medical Research, Royal Perth Hospital, Perth, Australia. email@example.com
BACKGROUND: Polyphenols can act as acceptors of methyl groups during the metabolism of methionine to homocysteine. This may result in elevations in plasma total homocysteine (tHcy) concentrations after ingestion of polyphenol-rich beverages such as tea. OBJECTIVES: Our major objective was to determine whether regular, moderate-to-high intakes of black tea alter tHcy concentrations. We also assessed the relation between the degree of O-methylation of tea-derived polyphenols and the change in tHcy with regular ingestion of tea. DESIGN: Twenty-two subjects completed a randomized, controlled crossover study. Subjects consumed 1250 mL black tea/d (5 cups each containing 2 g tea leaves in 250 mL boiled water) and 1250 mL hot water/d for 4 wk each. Fasting tHcy concentrations and 24-h urinary excretion of 4-O-methylgallic acid (4OMGA, the major O-methylated metabolite of gallic acid) were measured at the end of each period. 4OMGA was used as a marker of overall O-methylation of tea-derived polyphenols. RESULTS: Black tea did not significantly alter mean (+/- SEM) tHcy concentrations (9.9 +/- 0.5 and 10.0 +/- 0.5 micro mol/L for the hot water and black tea periods, respectively). However, the increased excretion of 4OMGA as a consequence of black tea consumption was positively associated with the change in tHcy from the hot water period to the black tea period (r = 0.55, P = 0.008). Subjects in the bottom quartile of increase in 4OMGA excretion had a significant decrease in tHcy (-0.28 +/- 0.10 micro mol/L; P = 0.046), and those in the top quartile had a significant increase in tHcy (0.78 +/- 0.16 micro mol/L; P = 0.005). CONCLUSIONS: Overall, regular ingestion of black tea did not alter mean tHcy concentrations. However, individual differences in O-methylation of polyphenolic compounds may influence the ultimate effects of black tea on tHcy.
Randomized Controlled Trial
PMID: 12663290 [PubMed - indexed for MEDLINE]
[iv] Am J Clin Nutr. 2001 Mar;73(3):532-8.
Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans.
Olthof MR, Hollman PC, Zock PL , Katan MB .
Division of Human Nutrition and Epidemiology, Wageningen University , Wageningen , Netherlands . firstname.lastname@example.org
BACKGROUND: In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d. OBJECTIVE: We studied whether chlorogenic acid affects plasma total homocysteine concentrations in humans. For comparison we also studied the effects of black tea rich in polyphenols and of quercetin-3-rutinoside, a major flavonol in tea and apples. DESIGN: In this crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic acid, 4 g black tea solids containing approximately 4.3 mmol polyphenols and comparable to approximately 2 L strong black tea, 440 mg (0.7 mmol) quercetin-3-rutinoside, or a placebo daily. Each subject received each of the 4 treatments for 7 d, in random order. RESULTS: Total homocysteine in plasma collected 4-5 h after supplement intake was 12% (1.2 micromol/L; 95% CI: 0.6, 1.7) higher after chlorogenic acid and 11% (1.1 micromol/L; 95% CI: 0.6, 1.5) higher after black tea than after placebo. Total homocysteine in fasting plasma collected 20 h after supplement intake was 4% (0.4 micromol/L; 95% CI: 0.0, 0.8) higher after chlorogenic acid and 5% (0.5 micromol/L; 95% CI: 0.0, 0.9) higher after black tea than after placebo. Quercetin-3-rutinoside did not significantly affect homocysteine concentrations. CONCLUSIONS: Chlorogenic acid, a compound in coffee, and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid could be partly responsible for the higher homocysteine concentrations observed in coffee drinkers. Whether these effects on homocysteine influence cardiovascular disease risk remains to be established.
Randomized Controlled Trial
PMID: 11237928 [PubMed - indexed for MEDLINE]