IH636 (Grape Seed Extract): In Search of a Natural AI or SERM

I have been looking for an alternative to synthetic SERMs and AIs given their requirement for a prescription in the West. There's a lot of promising research in this space, and I'll be covering a few different compounds in the next few weeks. As for Grape Seed Extract being that alternative, it's too early to say with conflicting data between rats and ladies, and no data as to its effects on e2 in men. It is worth mentioning that it does have marginal evidence for controlling edema, heart rate and systolic blood pressure.

The Case For A Natural AI

AI's were developed primarily for use in cancer treatments, specifically breast cancer where controlling estrogen is the determining factor on if the compound is effective is not. Happily, PEDs use have a similar criteria, and we can look at the work that's being done in breast cancer (which is of high quality and volume) for our own parallels.

Grape Seed Extract is documented in several studies to be an inhibitor of aromatase.


When it was trialed in 46 postmenopausal women, who were given daily doses of 200, 400, 600, or 800mg for 12 weeks. At all doses, on average only minor reductions in e2 were achieved (2.5%-5.3%).


In a clinical trial, twenty-nine men were treated with GSE 600 mg per day for 3 months. FSH, LH, and testosterone levels were evaluated both at the beginning and at the end of the study. LH & test levels were unchanged, but FSH significantly increased from 3.53u/l to 4.3u/l. AIs do increase FSH so this could be an indicator that it is effective in men . Its a stretch at this point, without direct e2 measurements it's just speculation.

There are open trials right now directly testing grape seed extract in men for the purposes of AI... and so we wait for the results to be released... in like 2028.

Safety + Side Effects

In this study, rats were provided IH636 at levels of 0 (control), 0.5, 1.0, or 2.0% of dietary intake, for a period of 90 days. There were no significant changes in clinical signs, hematological parameters, organ weights, ophthalmology evaluations, or histopathological findings.

Interestingly, a significant increase in food consumption was observed in male and female rats provided the grape seed extract diets compared to that of the control rats, especially in male rats consuming 2.0% grape seed extract. This effect was not accompanied by increases in body weight gains.

Grape seed extract appeared to increase the insoluble fraction of the diet (i.e. the amount of food not digested and passed as waste).

No significant adverse effects that can be tied to the compound have been seen in humans.

So What?

It's unfortunate, but there's not enough data or trials done involving men for us to draw any conclusion here. This remains an area of interest.

Explanations for the lack of success in humans range from:

  • BMI (50% of patients in the 800mg group were obese), shitty diets / uncontrolled caloric intake
  • female hormones / natural production of e2
  • dose too low
  • method of administration. To date, it's been taken orally. Experiments in the future should include it as an injection (/u/MezDez), or boofing it.

Or, it's just not that effective in humans, as compared to rats. I'm skeptical of this explanation, but it's possible I suppose.