What are the side effects of long term Quercetin supplementation? Any hormonal affects?

The short version: the retrieved evidence shows no long-term human safety trials for quercetin supplementation, and the hormonal data is limited to animal studies that suggest it can affect reproductive and thyroid hormone pathways.

The evidence you get is almost entirely from animal and in vitro studies, not from long-term human trials. One rat study found that quercetin upregulates the CREM gene and restores reproductive hormones (LH, FSH, testosterone) after cyanide-induced damage [2]. That tells you quercetin can influence the endocrine system, but it does not tell you what happens in a healthy person taking it for months or years. Another mouse study on obesity showed quercetin altered TSH and T4 levels, though the direction depended on the other compounds given alongside it [3]. These are signals that hormonal effects exist, not a safety profile.

The human data that exists is short-term. A 16-week trial in 41 people with type 2 diabetes using 220 mg of purple passion fruit peel extract (which contains quercetin) reported no adverse events [1]. That is a small, short study in a sick population, not a test of pure quercetin in healthy people over years. A 3-month trial in 127 people with fatty liver disease used quercetin alongside other drugs and reported improved liver markers, but again, short duration and no long-term follow-up [5].

The mechanistic evidence raises questions. Quercetin is metabolized by COMT, the same enzyme that breaks down catechol estrogens and dopamine [4]. In theory, high-dose long-term quercetin could compete for COMT and alter estrogen metabolism or neurotransmitter balance. The retrieved studies do not test this in humans.

My call: the evidence does not support a conclusion about the safety of long-term quercetin supplementation in humans, and the animal data suggests hormonal effects are plausible but unquantified. Confidence: low.