Pregnenolon part 3 – Supplement and information summary

Cara Marshall

In addition to the main functions, such as increasing steroid hormone production and improving the condition of the nervous system, pregnenolone also has several minor advantages regarding sleep quality, immune system activity and addiction to certain drugs. Before starting supplementation, it’s important to get acquainted with all aspects of the product to have complete control over what the supplement does with our body.

    What else can you expect from pregnenolone?

    A large part of society is struggling with sleep problems that come up for a number of reasons - too late to bed, using blue light, late stress, and so on. This is one of the most underrated and at the same time very serious factors affecting the deterioration of our health by weakening insulin sensitivity, increase blood pressure, suppress sexual hormones, or decrease cognitive ability. According to the researchers, pregnenolone and its metabolites can improve sleep quality by prolonging deep, slow-wave sleep [1,2], which can improve night-time regeneration and improve general health and memory formation.

    In some cases, pregnenolone can also be used to modulate the Th1 and Th2 arms of the immune system's cytokine balance. This steroid can contribute to suppression of Th2 cells, which is potentially beneficial in asthma, allergies, or some cancers [3]. Moving on to immunology and cancer, it is worth mentioning the positive effects of pregnenolone in the treatment of gliomas by increasing the apoptosis of tumour cells, as confirmed by studies [4].

    Research done on rats indicates that pregnenolone may reduce alcohol consumption [5,6]. This is another consequence of the interaction of neurosteroids with the GABA system, as this reduces the need for GABA-induced alcohol-induced effects because our natural GABA works better.

    Pregnenolone is also a potent inhibitor of CB1 receptors for the cannabinoid system [7], thereby limiting the effect of THC contained in marijuana and synthetic cannabinoids such as AB-Chiminaca or AB-Fubinaca. This property can be useful for people struggling with addiction to cannabinoids who would like some help with the addiction.

    The key questions, whether and when to take supplements with this steroid?

    It is most worthwhile as soon as they come to this indication, and these are few. The first, most obvious reason for substitution is the decline of hormones that progresses with age, especially after menopause or andropause, to improve the quality of life, reduce the risk of illness, including those affecting the nervous system and improve overall health.

    However, elderly age is not the only indication, as younger people may also struggle with certain disorders associated with insufficient hormone production. Common causes of such problems are chronic starvation, especially when combined with above-average training intensity (e.g. when preparing for a competition) and excessive psychological stress associated with everyday life. It’s worthwhile to support ourselves with supplements until we can find and fix the cause of the problem.

    The next situation in which pregnenolone is worthy of attention are adrenal dysfunctions that sabotage the production of hormones that are important to us, such as cortisol or DHEA. For many people it is surprising that one can worry about low cortisol. Well, it turns out that deficiency of this steroid is as dangerous as its excess, so it is worth to take care of its proper level.

    Less well-known indication for supplementation may also be genetic disorders. One is the variant rs6971 of the TSPO gene [8], which affects the less efficient synthesis of pregnenolone from cholesterol, which seems to be an obvious prerequisite for the implementation of supplementation.

    Is pregnenolone safe?

    The vast majority of studies indicate no side effects and overall good tolerance of the supplement. Minor negative effects such as excessive drowsiness or headache have been reported sporadically, usually in patients with severe illness who may be significantly more sensitive to the effects of any means. It is also worth mentioning that it is a natural steroid synthesized also in our own body, so it is well known by our body. We can therefore say that pregnenolone is a safe supplement.

    However, as with all other things, it’s worth keeping some precautions. Firstly, the results of hormone testing should be monitored to appropriately adjust the dosage of the supplement and not lead to excessively high levels of hormones. Another way to achieve maximum benefit is to include supplementation that allows you to manipulate pregnenolone metabolism pathways. For example, the use of aromatase inhibitors such resveratrol can reduce the growth of estradiol and oestrone, thereby increasing testosterone and androstenedione increase, which is particularly interesting for men. Potentially, cortisol suppression seems to be beneficial if we do not complain about adrenal insufficiency. Such treatment should also provide for greater hormone growth, which will give us more beneficial effects, limiting those potentially harmful in excess.

    Read more

    If you missed earlier parts of this series regarding pregnenolone, first one focused on what pregnenolone actually is, and second one on pregnenolone benefits for brain and nervous system. Be sure to check them!


    1) Terán-Pérez G et al. Steroid hormones and sleep regulation. Mini Rev Med Chem. 2012 Oct;12(11):1040-8.

    2) Steiger A et al. Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation. Brain Res. 1993 Jul 2;615(2):267-74.

    3) Bidesh Mahata et al. Single-Cell RNA Sequencing Reveals T Helper Cells Synthesizing Steroids De Novo to Contribute to Immune Homeostasis. Cell Rep. 2014 May 22; 7(4): 1130–1142.

    4) XIAO XIAO et al. Pregnenolone, a cholesterol metabolite, induces glioma cell apoptosis via activating extrinsic and intrinsic apoptotic pathways. Oncol Lett. 2014 Aug; 8(2): 645–650.

    5) Rezvani AH,  Levin ED. Assessment of pregnenolone effects on alcohol intake and preference in male alcohol preferring (P) rats. Eur J Pharmacol. 2014 Oct 5;740:53-7.

    6) J. Besheer et al. Pregnenolone and ganaxolone reduce operant ethanol self-administration in alcohol-preferring P rats. Alcohol Clin Exp Res. 2010 Dec; 34(12): 2044–2052.

    7) Monique Vallée et al. Pregnenolone Can Protect the Brain from Cannabis Intoxication. Science. 2014 Jan 3; 343(6166): 94–98.

    8) Costa B et al. The spontaneous Ala147Thr amino acid substitution within the translocator protein influences pregnenolone production in lymphomonocytes of healthy individuals. Endocrinology. 2009 Dec;150(12):5438-45.


    Tags: cortisol, dhea, hormones, oestradiol, pregnenolon safety, pregnenolon side effects, pregnenolone, testosterone

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