# Implications of MTHFR Polymorphisms in Women receiving a Combination of Green Tea Extract and Fertility Promoting Drugs on Serum Folate Levels

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $159,900

## Abstract

Project Summary
Uterine fibroids (i.e. leiomyomas) affect 30 to 50% of reproductive-age women that are strongly associated with
reducing the likelihood of pregnancy (RR=0.3-0.7) when compared to unaffected women. Surgical removal of
fibroids can restore fertility, however, the benefits are often short due to a high recurrence rate of fibroids.
Post-operative consequences are another concern as adhesions can negatively impact a woman’s fertility and
overall health. Pharmacological approaches to reduce uterine fibroids include hormonal therapies, however,
they also lead to pharmacologically-induced menopause thereby preventing pregnancy. For this reason, there
is a critical and unmet need to identify safe and orally bioavailable non-hormonal and non-surgical treatment
options for women with fibroids that distort the uterine cavity. One such approach is being investigated in the
parent grant (1R01HD100367) evaluating the hypothesis that EGCG can reduce fibroid size and increase the
likelihood of pregnancy. Briefly, the parent grant is supporting a placebo-controlled clinical trial to evaluate live
birth outcomes for women with unexplained infertility who have uterine fibroids. The objective of this proposal
is to complement the parent project (1R01HD100367) to identify clinically relevant mechanisms of folate
depletion and determine if a clinically relevant natural product drug interaction (NPDI) exists between fertility
treatment and green tea extract. a consortium as described in RFA-HD-19-022 was formed. Yale will serve as
the DCC and a clinical site, John Hopkins will coordinate the single IRB and be a clinical site. Investigators at
UIC have experience with EGCG and clinical trials and will serve as lead PI. MTHFR represents the most
studied enzyme in the folate pathway for neural tube defects and with strong evidence that polymorphisms
decrease enzyme activity it represents a clinically relevant target. Another critical enzyme in the folate pathway
is dihydrofolate reductase (DHFR) which has been shown to be inhibited by select small molecules including
green tea catechins. We are proposing to stratify subjects by wildtype MTHFR, MTHFR (C677T), and MTHFR
(A1298C). The prevalence of MTHFR mutations can range from 30 to 40% in the American population for
C677T and ~50% for A1298C. Green tea extract has been reported to decrease folic acid levels through two
mechanisms that include the inhibition of dihydrofolate reductase (DHFR) and decreasing the bioavailability of
folic acid. Our hypothesis is that green tea catechins have weak inhibitory DHFR properties that may increase
the risk of folic acid depletion in women expressing known MTHFR polymorphisms. To test our hypothesis, we
have proposed two specific aims. Specific Aim 1. To determine if MTHFR polymorphisms increase the risk of
folate depletion in women receiving green tea extract. Specific Aim 2. To determine if a clinically relevant
natural product-drug interaction (NPDI) exists in women ...

## Key facts

- **NIH application ID:** 10156039
- **Project number:** 3R01HD100367-02S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Ayman Al-Hendy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $159,900
- **Award type:** 3
- **Project period:** 2019-09-26 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156039

## Citation

> US National Institutes of Health, RePORTER application 10156039, Implications of MTHFR Polymorphisms in Women receiving a Combination of Green Tea Extract and Fertility Promoting Drugs on Serum Folate Levels (3R01HD100367-02S1). Retrieved via AI Analytics 2026-07-19 from https://api.ai-analytics.org/grant/nih/10156039. Licensed CC0.

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