Pregnenolone effects on skin and hair

This is a knowledge dump of everything I've learned about pregnenolone as a topical scalp treatment. I make topical solutions in oil or EtOH with under about .5% pregnenolone, the highest concentration I can make without saturation at room temperature. For the oil solution I use coconut oil due to its stability and antioxidant properties. I cannot report direct, observable benefits to my scalp, but I have not been using it for a very long time. I (and others I've recommend it to) have used it as a powerful anti-itch remedy for such conditions as poison ivy.

As a practical matter it is difficult to make a pregnenolone solution in oil or water, and I have not found the breakdown temperature of pregnenolone. In general it seems that steroids start breaking down much over 150C, and I try to avoid going over 100C when mixing a solution. I have not been successful making a vitamin E combination and am not sure why many people try to mix it with that particular vitamin. There is a valid reason to use vitamin D with pregnenolone, since that vitamin participates in production of some of its metabolites, but I don't mix it with my topical solutions but take it orally instead.

Skin is both a source and depot of pregnenolone, and some of its metabolites like DHEA are also produced in the skin. Both hormones are important to skin health, and both decline after adolescence and the decline rates are sufficiently predicable as to serve as reliable biomarkers of aging. Many of the effects of these hormones are closely related to skin maintenance and general health. It may be reasonable to deduce that the decline of these steroids is an important factor in skin aging. This may also be the rationale behind the use of pregnenolone in various commercial cosmetic preparations. Pregnenolone may be useful in a hair loss treatment regimen to the extent that it reduces or reverses skin aging, considering the extent to which hair loss is connected to skin aging. This is my rationale for using it.

Pregnenolone was discovered over 70 years ago and was used medicinally until it was replaced by synthetic corticosteroids, which are derived from pregnenolone. The synthetic derivatives and more powerful but have serious side effects. To my knowledge, pregnenolone has none of the more serious side effects of corticosteroids. My theory is that these side effects occur for the same reason synthetic corticosteroids are more powerful. The body cannot properly metabolize them, giving them a longer half live but also causing side effects. Some of the caution doctors have for corticosteroids may affect their opinions about pregnenolone. Early studies used as much as 500mg daily without adverse effects. One (unofficial) source claims that over 200mg causes liver problems, but I have not found any corroboration for this. Some medical web sites urge caution for all pregnenolone usage, claiming lack of safety and effectiveness data. In any case, topical use for scalp treatment is probably a low-risk route of administration. The only risk factor that seems to have a strong medical consensus is use by people with heart rhythm issues, but this may be allegorical and not based on studies or scientific evidence. Pregnenolone is a widely available supplement and there have been no reported deaths or serious complications, to my knowledge. DHEA, on the other hand, is much more widely used supplement since it is marketed as a weight-loss supplement. As an intermediate pro-hormone and weak anabolic steroid, it is more likely to cause serious side effects and probably deserves more caution when used as a supplement.

The FDA allows a very low percentage of pregnenolone in commercial cosmetics, much lower than the topicals I've been making and using. Since skin is a natural pregnenolone depot it seems unlikely that much systemic exposure results from topical use. In addition, pregnenolone topical serums intended for systemic effects have a much higher percentage of pregnenolone than the <.5% solutions I am using, and probably include various penetration enhancers. Although medicinal uses have used very high concentrations, in scientific (in vitro) studies, pregnenolone has been shown to have some strong effects in less than nanomolar concentrations. Some neurosteroidal effects are reported from amounts as low as a few dozen molecules. Its effects in steroid recepters, however, are weaker than any of its derivatives, although it as a weak agonist on all its derivative hormone receptors. This may explain why topical pregnenolone has cortisol effects on skin inflammation.

Although it is produced endogenously, pregnenolone is also a natural part of the human diet. For example, compared to modern diets, primitive societies got more pregnenolone in their diets from organ meat. Pregnenolone may be one of those nutrients which, like vitamin D, become quasi-essential under particular conditions, and aging may be one such conditions. Other conditions causing pregnenolone depletion include disease, injury, stress and pain. Since pregnenolone is the source of most hormones, this depletion has systemic adverse effects. These conditions, if prolonged, tend to drive more pregnenolone into the cortisol metabolic pathway, resulting increasing inflammation and immunosuppression combined with a reduction of tissue regeneration and maintenance as mediated by other hormones, likewise depleted by pregnenolone deficit The resulting additional cortisol production and pregnenolone depletion completes a vicious feedback cycle. Multiple glands, organs and hormone pathways become involved and are adversely affected, including skin. (Ray Peat goes into detail about the detailed mechanisms.) This process can occur as a short-term or long-term disorder, and when it happens lone-term, according to Peat, it effectively becomes a permanent condition synonymous with aging.

Pregnenolone and its metabolites are vital to all organs, tissues and systems of the body. The visible condition of the skin may be a indirect indicator of internal organ health and status. Pregnenolone is the most important and broadly active neurosteroid in the brain. In addition to its steroidal functions, it has anti-oxidant, neuroprotective and anti-inflammatory effects. It is one of the most important chemicals in the body and certainly the most important steroid. Depletion is a factor, possibly the chief factor, in aging-related disorders. It has broader effects on the nervous and endocrine systems than any other steroid.

The peptide GHK also declines with age and like pregnenolone, its decline serves as a reliable age biomarker. GHK is vital to all cell metabolic processes at all phases of the cell life cycle. Correspondingly, it is calculated to be the most active chemical in the body based on MITs Connection Mapping (gene expression) simulator. (See Loren Pickart's papers on the subject.) I wrote about it in another post, but it's mentioned here to contrast it with the mechanisms of action of pregnenolone. Pregnenolone triggers steroid receptors and acts on a systemic basis. in contrast GHK moderates through gene expression and DNA maintenance. It is vital to intra-cellular biochemical signaling, analogous, though opposite in scale, to how pregnenolone acts on a systemic level. Since both are depleted with aging and both, by that depletion, as strongly associated with aging, it raises the chicken and egg question of which depletion comes first and causes the other, or whether both occur together. As a precaution I have added GHK-cu to my regimen, occasionally cycle between them to detect any differences in effects.

Given its availability, low cost, safety profile, extensive scientific and medical scrutiny, and its long history of human use, I see no reason to exclude pregnenolone from a normal hair treatment regimen. It's likely that in some cases, it is critical for scalp recovery. I also use it as a dietary supplement but topical use may be orders of magnitude more efficient. Since it is naturally and typically produced in the organs where it is used (in the brain for example) it makes sense to apply it in a more targeted way, in this case topically. Oral pregnenolone is quickly converted in the liver to the storage metabolite, pregnenolone sulfate, and slowly distributed throughout the body. Topical application skips this step. Compared to many supplements, pregnenolone has strong scientific evidence as a treatment for maintaining general skin heath, especially for aging persons. It does not have much human trials data, however, like GHK-cu for example. For this reason, I use both of them to "cover my bases."

In addition to their steroidal and anti-aging effects on skin, pregnenolone and DHEA have anti-inflammatory and anti-oxidant effects. I have tried them together but at this point only use the pregnenolone, since learning that DHEA is produced from it naturally in the skin. Topical pregnenolone may offer some sunscreen effect, but I am not sure of my sources for that. It would take more time than I have to cite sources for all of this, and it is likely that some of my facts are incorrect, but I hope this helps somebody. My source for bulk pregnenolone is Health Natura. I am not connected to them in any way and cannot vouch for the quality of their product, but it seems to work and is the only source I can find at the moment.