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    NRF2 much of a good thing (December 2017) sulforaphane stm.sciencemag.org
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This might be an important detail for people using sulforaphane to boost NRF2 expression. The benefits of NRF2 expression are pretty well known, but from this article it seems like having NRF2 strongly activated all the time might have some downside effects in the long-term. I used to take sulforaphane every day, but now I’m thinking about spacing my broccoli sprouts out a little bit, with the goal of letting NRF2 expression cycle up and down over time, hopefully deriving the benefits without incurring tissue damage. Have I misunderstood the article, or am I possibly overreacting? Personally, I’m still sold on the benefits of sulforaphane, but maybe it’s worth looking at spacing the doses out (exactly how far, I don’t really know). Anyone have any thoughts, rebuttals, or suggestions?

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    Trying to wrap my head around the research paper. Here if you can get through the paywall: DOI: 10.1210/en.2017-00752 From the abstract: We investigated the role of nuclear factor erythroid 2–related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). …

    These data identify a mechanism, Nrf2-mediated stimulation of intrarenal RAS gene expression, by which chronic hyperglycemia induces hypertension and renal injury in diabetes.

    So, if I understand correctly, these are type 1 diabetic mice. Directly activating Nrf2 using oltipraz in these diabetic mice resulted in hypertension and kidney damage.

    I’m not sure how generally we want to interpret these results. Although if you are a type I diabetic with uncontrolled hyperglycemia you would probably want to keep an eye on your blood pressure in the unlikely event you were taking oltipraz.

    What about sulfurophane? No idea. Not covered in this paper.

    Well, okay, since we are basically stumbling around in a dark room trying to figure out what is happening, let’s take the worst possibility – that sulfurophane acts as a Nrf2 activator in exactly the same mode as oltipraz. In that case don’t use either if you are hyperglycemic. Get your hyperglycemia under control before inducing Nrf2 in your kidneys.

    Although, chances are that oltipraz and sulfurophane are doing 10 other things beside dis-inhibiting Nrf2 and some of these 10 other things mitigate or aggravate damage-causing processes in some kidney cells in the presence of hyperglycemia.

    If you are doing Time Restricted Eating, you are already spacing out the sulfurophane. I’m not sure what sulfurophane’s half-life is, though.

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      It should be noted that other supplements plus exercise and fasting also stimulate NRF2. Compulsive biohackers (probably most of us) doing all of these things may be chronically overactivating the NRF2 pathway. A couple of washout days a week may keep things in balance.

      https://drjockers.com/nrf2-benefits/

      https://www.selfhacked.com/blog/about-nrf2-and-natural-ways-to-increase-it/