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5α-Dihydroprogesterone (5α-DHP) - Potent Role In Neurodegenerative Conditions

  1. While researching saturated steroids and their effects on the brain, I noticed a number of highly promosing studies demonstrating benefit of such steroid for a variety of neurodegenerative conditions such as MS, ALS, Alzheimer, Parkinson, etc. Ray has written extensively on the topic of progesterone and its protective role in the brain, including therapeutic effects for a number of these conditions. There are a few large human clinical trials going on right now using progesterone to treat traumatic brain injury (TBI), especially in soldiers and athletes. Successful humans trials have also been conducted with progesterone for Alzheimer disease, dementia, stroke, depression, and even cancer.
    A number of studies have shown that the degree of saturation of a steroid directly correspond to its beneficial effects in brain and actually all other tissues. So, I did some research on progesterone and its saturated metabolite 5α-DHP, and as it turns out this steroid may have promise for all of the above mention conditions. It is apparently known in research circles to treat animal models of MS, and human studies have shown the dramatic decline of saturated steroids like DHT and 5α-DHP in the CSF of MS patients as well as patients with other neurological conditions. The studies below give some background on the beneficial effects of 5α-DHP for these conditions.

    1. Multiple Sclerosis (MS) and other demyelination diseases
    5a-Pregnane-3,20-dione | CAS 566-65-4
    "...5a-Pregnane-3,20-dione exerts neuroprotective effects in chronic autoimmune encephalomyelitis (EAE). The neuroactivity of the steroid acts as a therapeutic agent for multiple sclerosis."

    Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients. - PubMed - NCBI
    Neuroprotective effects of progesterone in chronic experimental autoimmune encephalomyelitis. - PubMed - NCBI
    Progesterone derivatives are able to influence peripheral myelin protein 22 and P0 gene expression: possible mechanisms of action. - PubMed - NCBI
    The action of steroid hormones on peripheral myelin proteins: a possible new tool for the rebuilding of myelin? - PubMed - NCBI
    Neuroactive steroids and peripheral myelin proteins. - PubMed - NCBI
    Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber lo... - PubMed - NCBI
    Effects of neuroactive steroids on myelin of peripheral nervous system. - PubMed - NCBI
    Neuroactive steroids influence peripheral myelination: a promising opportunity for preventing or treating age-dependent dysfunctions of peripheral ... - PubMed - NCBI
    Actions of progesterone and its 5alpha-reduced metabolites on the major proteins of the myelin of the peripheral nervous system. - PubMed - NCBI

    2. Diabetic neuropathy
    Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: a multimodal analysis. - PubMed - NCBI

    3. Alzheimer Disease (AD)

    4. Traumatic nerve injury

    5. Amyotropic Lateral Sclerosis (ALS)

    6. Miscellaneous brain protection
  2. It was only published a week ago, so I guess you can be forgiven. What happened to Euraeka by the way?
  3. Not much commercial interest in it. Tried to get some money for it but back in 2009 everybody said there is no money in news. It may be different today, so I may resurrect it but I need to code up a frontend for it and that takes time (which I don't have currently). But I keep the algorithms running on the backend and this how I find most of interesting popular press articles that I post on the forum. I had Euraeka trained on some articles I like and now it just recommends 100 new ones every day from which I select what ti post here.
  4. Any advice on what biomarkers should be monitored before, after and during the administration of 5a-DHP to evaluate the safety and efficacy of 5a-DHP and to determine what is the best treatment regime of 5a-DHP for a rat that might be suffering from Parkinson's disease?

    Here is what I have come up with;

  5. Also in a discussion with a doctor about Allopregnanolone, I have been told that elevating this substance directly is not necessary given the current treatment that is being administered.

    The female mammal in question is currently receiving some very advanced stem cell therapy and it has no doubt improved her condition. The Doc claims that this has a more powerful stem cell effect than allopregnanolone which he claims also improves conditions through the proliferation of stem cells.

    This study would seem to demonstrate this,
    The Neurosteroid Allopregnanolone Promotes Proliferation of Rodent and Human Neural Progenitor Cells and Regulates Cell-Cycle Gene and Protein Expression.

    It should be noted that the stem cell treatment she is receiving is not directly targeted at increasing dopamine cells in the brain but rather increasing all levels of stem cells throughout the entire body. It is known as stem cell transplant therapy.

    However, I believe that the increase of allopregnanolone via 5a-DHP, would have additional benefits that are not currently afforded by current stem cell therapy treatment. Because I do not believe that the neuroprotective benefits of an increase of allopregnanolone stem only from neural cell generation but other factors as well such as lowering of chronic stress factors and improving metabolism.
  6. So, you think the new and largely unproven stem cell therapy, which also has remarkable parallels to cancer cell functionality, is safer than allopregnanolone? Also, the claim about allopregnanolone working through stem cells is largely unproven and I am not even sure where the doctor got this information from. If you have studies from that doctor about the allopregnanolone and stem cell connection please post here.
  7. The fact that stem cell therapy has parallels to cancer cell functionality is news to me and deeply concerning. I was very sceptical about the stem cell allopregnanolone connection as he did not provide me any studies. The only one I was able to find that might be relevant was the study I posted in my original post, The Neurosteroid Allopregnanolone Promotes Proliferation of Rodent and Human Neural Progenitor Cells and Regulates Cell-Cycle Gene and Protein Expression. But perhaps I misunderstood it.

    When you say parallels to cancer, are you implying that stem cell therapy could increase the risk of cancer? That would be highly ironic in this case as his main business is using stem cell and bone marrow transplants to treat cancer. You can see for yourself here, South Florida Bone Marrow/Stem Cell Transplant Institute. As far as I understand it his treatment helps for cancer by raising the bodies natural defences (primarily t-cells) to fight off the cancer independently of chemotherapy or other traditional cancer treatments. He has shown me examples of how when the natural t-cells of people go below a certain count cancer becomes very likely and that raising them back up through stem cell and bone marrow transplants helps the body to fight off cancer. A lot of this is way outside my depth of understanding. While it sounds good on paper, for all I know raising t-cell levels could just be another chronic stressor on the body. Although he does appear to have some pretty powerful results with regards to cancer treatment.

    I must say he has been very open for the most part to alternative views that are outside the mainstream of medicine. He was fully aware of red light therapy when I mentioned it to him and is strongly in favour of it for assistance in treating neurological conditions. He does not buy into genetic determinism at all when it comes to disease and believes virtually all chronic health conditions from cancer to heart disease are caused by environment rather than genetics. He also took on board my suggestions for b vitamins as a potential treatment. He also had her go on thyroid which I think has greatly helped her. His measurement so far for progress in the treatment of Parkinson's certainly seems to me to be better than the traditional mainstream doctor. He has done tests for heavy metal toxicity and a number of other bio-markers to try and determine what the chronic environmental factors might have been that led to PD. He doesn't always get it right though as he recommended fish oils to help with the treatment of PD. Which was odd because he was vehemently against PUFA but in favour of fish oil. I quickly put that to bed when I showed him that fish oil is just another PUFA.

    He always listens to my feedback and responds to my email correspondence. Anyway done defending him haha. I'll ask him if he has any studies about allopregnanolone and stem cells.

    One final thing I would say there has been improvement as from direct observance and correspondence with said mammal. Less tremors, more stable and reduction in brain fog. For my part I think the treatment is having a benefit but considerably less than what might be possible with a more peat-centric approach. Hence why I am strongly pushing for 5a-DHP and trying to get as much info as possible showing the benefit of allopregnanolone comes from actions outside of stem cell proliferation.
  8. I am not saying the therapies he promotes are not legitimate. I am just saying that they are largely untested, unlike allopregnanolone and the statement about allopregnanolone working the same way as the stem cell treatment is suspect (to me at least). Anyways, if this is your doctor and you trust him then best to go by what he says. Here are some things to consider and show him.
    Stem Cells Might Cause Cancer
    Hundreds of companies in the U.S. are selling unproven stem cell treatments, study says
  9. Thanks haidut :thumbsup:
  10. Is this why 5a-DHP can become less effective over time?

    Tolerance to allopregnanolone with focus on the GABA-A receptor

    There are physiological conditions in which allopregnanolone production increases acutely (e.g. stress) or chronically (e.g. menstrual cycle, pregnancy), thus exposing the GABA-A receptor to high and continuous allopregnanolone concentrations. In such conditions, tolerance to allopregnanolone may develop. We have shown that both acute and chronic tolerances can develop to the effects of allopregnanolone. Following the development of acute allopregnanolone tolerance, there is a decrease in the abundance of the GABA-A receptor α4 subunit and the expression of the α4 subunit mRNA in the ventral-posteriomedial nucleus of the thalamus. Little is known about the mechanism behind allopregnanolone tolerance and its effects on assembly of the GABA-A receptor composition. The exact mechanism of the allopregnanolone tolerance phenomena remains unclear. The purpose of this review is to summarize certain aspects of current knowledge concerning allopregnanolone tolerance and changes in the GABA-A receptors.
  11. This is one mechanism, yes. All receptor agonist would tend to induce de-sensitization when used chronically. But the liver adaptation is also probably involved. This is why I think the lower doses as per the studies (5-6 mg) is optimal on a daily basis as it has almost the same effects on prolactin and estrogen but at that low dose it is not likely to induce desensitization or liver adaptation. If a higher dose is used I would to every other day or take period breaks for a week every 3-4 weeks.
  12. Makes sense.
    Funny you mention liver adaptation, that is why actually got me into looking into that study originally due to finasteride being first metabolized by the liver (and liver toxic) and the 5AR enzyme being there as well. Meaning if adaption to fin could of taken place, the first place could be the liver (the enzymes being downregulated there). Hence why elevated enzymes, poor liver function (poor conversion of T4 to T3, poor clearance of estrogen, poor glycogen storage etc.). Although liver enzymes aren't that accurate of liver function, still could be something to take a look at. I can't see it be only being related to the brain ONLY, when people can barely go on hour due to such horrible glycogen storage.

    Another area caffeine/K2/thyroid/niacinamide/thiamine helps.