It's hard to imagine a more complex network of relationships than the human hormonal economy. We have a vast array of steroids that transmit information between different organs and control the work of our brain, regulating its activity. Each of the steroids involved in this festival of life has a common denominator - the substance from which they are formed. This is pregnenolone.

• What is pregnenolone?
• What effects can pregnenolone supplementation bring?
• Pregnenolone dosage in supplementation
• What to watch out for.

What is pregnenolone?

Pregnenolone is the precursor of all steroids in the human body. He, in turn, is produced from cholesterol in the mitochondria. The main organs where pregnenolone is produced are the gonads, adrenal glands and brain. Each of the steroids naturally circulating in our system has its origin in pregnenolone.

In the US market, pregnenolone is sold in the form of dietary supplements.

What effects can pregnenolone supplementation bring?

The effects are due more to the metabolites of pregnenolone than to pregnenolone itself. For this reason, pregnenolone is more considered a precursor than an active steroid per se. We can consider all steroids as its metabolites, but the most important are those produced first, such as pregnenolone sulfate, pregnanolone and allopregnanolone, DHEA and its sulfate, and progesterone, among others. Each of these metabolites is a neurosteroid. This means that they are active in the brain and regulate its function. This is why pregnenolone is readily used in various types of brain disorders, such as mood or memory impairment, and sometimes in various neurological diseases.

One of the most important elements of the action of all these neuro-steroids is their effect on the activation or inhibition of GABA(A) and NMDA receptors. In this way, they influence the modulation of brain excitability. To a lesser extent, Sigma1 and CB1 (cannabinoid receptor) receptors are also affected.

The available reviews of pregnenolone on the web are very much in favor of its effect on improving memory. Scientific publications are not the strongest focused on this aspect, but there is no shortage of relevant rationale either. The aspect of improving memory and cognitive function requires further research to definitively state a beneficial effect in humans. At this point, reports are severely limited and yield mixed results, while there is much more and more promising data on animal models.

Many reports, both from scientific experiments and from practical user feedback, indicate an anti-anxiety effect and a reduction in mild depressive symptoms. In addition to its effect on memory, the mood-enhancing effect is one of the main reasons for using pregnenolone supplements. The neuroprotective and neuronal plasticity-enhancing effects are considered a significant benefit and also encourage those looking to use anti-aging supplementation. More advanced benefits include an analgesic effect and action against schizophrenia and psychosis.

Pregnenolone dosage in supplementation

The usual dosage ranges are wide. They can be closed in the range of 5-100 mg of pregnenolone per day. The universal rule of thumb is to use low doses to begin with and raise when needed, while the target dose is strongly dependent on the reason for including supplementation and even the age of the supplementing person. The older the person, the greater the need for the steroid precursor may be.

Pregnenolone supplements are available in various forms - capsules, tablets or lozenges.

What to watch out for.

The disadvantage of pregnenolone is that it is quite difficult to accurately predict its effect. By providing more of it in a supplement, we are simply providing a building block. What will be built from it is already the responsibility of our body. Steroid metabolism pathways are very elaborate and there may be differences between different individuals. Individual genetic predisposition regulates the strength of activity of various enzymes, so the proportion of steroids created from pregnenolone in each user may be different.

It is crucial, especially in the initial phase of supplementation, to watch your reaction carefully. If the decision is already made to supplement pregnenolone, it is a good idea to start with a minimum dose and gradually increase it as needed.

Sources:

• Vallée M, Mayo W, Le Moal M. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Brain Res Rev. 2001 Nov;37(1-3):301-12.
• Vallée M. Neurosteroids and potential therapeutics: Focus on pregnenolone. J Steroid Biochem Mol Biol. 2016 Jun;160:78-87. doi: 10.1016/j.jsbmb.2015.09.030. epub 2015 Oct 1. PMID: 26433186.