Vitamin K (MK-4), A, pregnenolone, progesterone as novel treatments for neurodegenerative conditions
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Surely a post that may aggravate the vitamin A opponents, but the results speak for themselves. The study found that vitamin K (MK-4) increased the expression of so-called microtubule associated protein 2 (MAP2), which is also a major target of the neurosteroids such as pregnenolone and (to a lesser degree) progesterone. Vitamin K activates the xenobiotic receptor (SXR) and vitamin A activates the retinoic acid receptor (RAR), and activation of both receptors is a prerequisite for inducing the MAP2 expression. That means a combination of vitamin K and A would be a viable option for people with neurological conditions who do not want to take steroids such as pregnenolone. For people who do not have an issue with pregnenolone, the combination of vitamin K/A plus pregnenolone or progesterone would probably be even more synergistic. The study claims that such treatments may be viable approaches to conditions such as Alzheimer Disease (AD), Parkinson Disease (PD), Huntington Disease (HD), and maybe even conditions such as ALS, MS, etc.
https://dx.doi.org/10.1021/acschemneuro.5c00111
https://phys.org/news/2025-09-vitamin-analogs-treatment-neurodegenerative-diseases.html
“…Neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease are characterized by the progressive loss of neurons. The resulting debilitating symptoms, such as loss of memory and cognition, and motor impairment, can significantly degrade patients’ quality of life, confining them to round-the-clock care. ”
“…While currently used drugs help alleviate symptoms, curative treatments are lacking, thus underscoring the need for novel therapeutic strategies. One such strategy involves the induction of neuronal differentiation, which can replenish lost neurons and potentially stall or reverse neurodegeneration. Vitamin K, a fat-soluble vitamin with established roles in blood coagulation and bone metabolism, has recently been implicated in neuronal differentiation and neuroprotection. However, the therapeutic activity of naturally active vitamin K compounds like menaquinone 4 (MK-4) may be insufficient for their application in regenerative medicine against neurodegenerative diseases.”
“…”Since neuronal loss is a hallmark of neurodegenerative diseases such as Alzheimer’s disease, these analogs may serve as regenerative agents that help replenish lost neurons and restore brain function.” To improve the potency of vitamin K, the researchers synthesized 12 vitamin K hybrid homologs conjugated with retinoic acid—an active metabolite of vitamin A known to promote neuronal differentiation, a carboxylic acid moiety, or a methyl ester side chain and compared the neuronal differentiation-inducing activity of the hybrid homologs. Vitamin K and retinoic acid regulate transcriptional activity via the steroid and xenobiotic receptor (SXR) and retinoic acid receptor (RAR), respectively. The researchers assessed SXR and RAR transcriptional activity in mouse neural progenitor cells treated with the newly synthesized compounds. Notably, the biological activity of vitamin K and retinoic acid was preserved in the hybrid homologs.”