Reversing osteoporosis with Nrf2

This 2021 rodent study made old females out of young females by removing their ovaries, which induced osteoporosis. They then demethylated the Nrf2 gene promoter with exercise, increasing its expression, which reversed osteoporosis:

“Nrf2 repression due to aberrant Dnmt elevation and subsequent Nrf2 promoter hypermethylation is an important epigenetic feature of osteoporosis (OP) pathogenesis.

Nrf2 promoter demethylation

Ovariectomized mice display increased femoral Dnmt1/3a/3b (Dnmts), Nrf2 promoter hypermethylation, and Nrf2 suppression, which promote oxidative stress (OS), osteoclastogenesis (OCG) and OP (dashed line).

Running exercise (RE, solid line) normalizes Dnmt aberrations, resulting in Nrf2 promoter demethylation, Nrf2 recovery and reduced femoral osteoporotic pathologies.

Nrf2 repression due to aberrant Dnmt elevations and associated promoter hypermethylation contributes significantly to epigenetic development of OP. RE effectively corrects epigenetic abnormalities and pathogenesis of OP.”

https://www.nature.com/articles/s41413-020-00128-8 “Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis”


Running an hour every day has effects on Nrf2 gene promoter expression similar to eating broccoli sprouts. A 2021 study Sulforaphane prevents angiotensin II‐induced cardiomyopathy by activation of Nrf2 through epigenetic modification found:

“SFN reduced Ang II‐induced CpG hypermethylation and promoted Ac‐H3 accumulation in the Nrf2 promoter region, accompanied by inhibition of global DNMT and HDAC activity, and a decreased protein expression of key DNMT and HDAC enzymes.”

A 2019 study Sulforaphane‑induced epigenetic regulation of Nrf2 expression by DNA methyltransferase in human Caco‑2 cells found:

“DNMT1 protein expression was inhibited by sulforaphane. Nrf2 promoter methylation decreased significantly in the sulforaphane group.

Sulforaphane may promote demethylation of the Nrf2 promoter region to increase activation of Nrf2.”


Per Week 6, my running days are over, though not walking, climbing, etc. Nrf2 activation with broccoli sprouts began after two weeks of self-quarantine more than a year ago.

Improving one’s own health provides sufficient rationale to act.

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