Pregnenolone Extract Additional Information
Pregnenolone is a neurosteroid that can be derived from the brain, gonads, or adrenal glands and is produced from cholesterol. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization. Myelin insulates nerve cells axons which increases the speed that information can travel across nerve cells. Additionally, pregnenolone acts as precursor to many other steroid hormones. (1,2,3)
Pregnenolone was originally synthesized by the Nobel Prize winning German biochemist, Adolf Butenandt. As a dietary supplement, Pregnenolone has become popular for being the “Mother/Grandmother of all steroid hormones”. (4,5) This nickname comes from its mechanism of production of other hormones. As a neurosteroid, pregnenolone has also shown promise for stimulating the brain and being neuroprotective. (1,2,3)
Pregnenolone Extract Benefits
Pregnenolone’s primary two benefits are as a cognitive enhancer and its action as a prohormone. (3) Pregnenolone, through its action of increasing levels of pregnenolone sulfate, is able to act as a signaling molecule and stimulate neuronal activity. (3,6) In a similar mechanism, pregnenolone is able to increase the growth of neurons.
Pregnenolone, as an excitatory neurosteroid, is able to modulate GABAᴀ and NMDA which has beneficial effects on cognition. (6) Pregnenolone also plays a role in the stabilization of microtubules, increase of ion flux, and dopamine release which plays a role in both cognition and mood. (9,10,11,12)
As a prohormone, a hormone that plays a role in the synthetization of other hormones, pregnenolone increases androgen, estrogen, progestogen, glucocorticoids, and mineralocorticoids. (see “How Pregnenolone Works”) (1,2,3)
In addition to boosting cognitive function and supporting hormonal balance, pregnenolone has added benefits that will be discussed further in “Pregnenolone Research” that includes:
- Stimulates deep sleep (17)
- Reduces anxiety (18)
- Balances immune system (19)
How to Use Pregnenolone
It is best to take pregnenolone early in the day on an empty stomach so that it gets absorbed more quickly. It is best to exercise when supplementing with pregnenolone to better assist in converting pregnenolone to other hormones.
For males, pregnenolone is commonly supplemented with aromatase inhibitors. This is to prevent pregnenolone from creating more estrogen.
Pregnenolone Dosing Instructions
Since pregnenolone affects your hormones, it is best to start with a smaller dose and see how it impacts your body. It is recommended that you start with 25mg or 50mg and work your way up to larger doses if needed.
A typical recommendation is 100mg per day and this should not be exceeded as side effects are more likely to occur at higher doses.
Pregnenolone Safety and Side Effects
Pregnenolone is reported very safe. Pregnenolone supplementation as high as 500mg per day was well tolerated in humans. (14) Additional mouse studies have shown that it would take a pregnenolone dose over 200mg/kg to cause toxicity. (20)
Pregnenolone is reported to be very well tolerated but the most commonly reported side effects include; insomnia, mood changes, headaches, and irregular heart rhythm. If taking pregnenolone at recommended doses, these side effects are very unlikely to occur.
Since pregnenolone is a prohormone, these side effects are related to a hormonal imbalance. Do not take pregnenolone with other hormones as it could increase the likelihood of side effects.
How Pregnenolone Works
Pregnenolone works as a neuroprotective agent and can enhance cognition by increasing allopregnanolone and pregnenolone sulfate. (6) Allopregnanolone is a naturally produced steroid that enhances GABAᴀ receptor responses which is major biological target of the inhibitory neurotransmitter γ-aminobutyric acid.
Pregnenolone sulfate is an excitatory neurosteroid that is a positive NMDA receptor modulator that is known to have cognitive enhancing effects. By acting in this way, pregnenolone can mitigate GABA dysregulation and NMDA hypofunction. (6) NMDA receptors interact with intracellular proteins by the subunits; NR1, NR2, and NR3. Within each of these subunits are other variations of the subunits. Pregnenolone sulfate potentiates glutamate and glycine-induced currents of NR1/NR2A and NR1/NR2B receptors. (3) Supplementation with pregnenolone is required to increase levels of pregnenolone sulfate as pregnenolone sulfate does not cross the blood-brain barrier. (7)
When pregnenolone binds to receptors, they elicit a series of reactions. (8) These reactions include:
- Stabilization of microtubules: Microtubules are structural cellular components that are involved in several areas of cell functioning but are inherently instable and are frequently disassembled. When pregnenolone binds with a protein, there is an increase in microtubule stability which is important in determining cell shape and polarity. (9)
- Increase of ion flux into cells: The function of ion channels is to allow specific inorganic ions to diffuse rapidly across the lipid bilayer of cells. As there is a large amount of sodium ions at the membrane surface, sodium ions are able to permeate the membrane via a flux. By pregnenolone increasing the number of fluxes, more sodium ions are able to permeate cells. In humans, sodium ions are important for neuronal function. (10,11)
- Dopamine release: Dopamine is a neurotransmitter that serves as a chemical signal between neurons. Most commonly associated with reward-motivated behavior, dopamine also aids in mood, attention, memory, and learning. By releasing dopamine, pregnenolone can aid all of these areas. (12)
Pregnenolone acts a precursor (or prohormone) in the biosynthesis of (1,2,3):
- Androgen: Steroid hormones that regulate the development and maintenance of male characteristics. Included in an androgen is Testosterone, the primary male sex hormone and anabolic steroid. Androgen is responsible for: testes formation, male pubertal development, spermatogenesis, fat deposition, muscle mass, aggression, and libido.
- Estrogen: The primary female sex hormone responsible for the development and regulation of the female reproductive system. The three major endogenous estrogens in females are estrone, estradiol, and estriol. Estrogen is responsible for: the formation of female secondary sex characteristics, increasing uterine growth, protein synthesis, increasing HDL, decreasing LDL, promotes lung function, ovulation, and sexual behavior.
- Progestogen: A class of steroid/sex hormones that activate the progesterone receptor. Progestogen is responsible for: the male and female reproductive systems, involved in the regulation of menstrual cycles, maintenance of pregnancy, preparation of mammary glands, spermiogenesis, and sperm capacitation.
- Glucocorticoids: A class of corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. Glucocorticoids are responsible for: regulation of glucose metabolism, synthesis in the adrenal cortex, feedback mechanism in the immune system which reduces inflammation, and impact fetal development.
- Mineralocorticoids: A class of corticosteroids that are produced in the adrenal cortex that influence electrolyte and fluid balance. Mineralocorticoids are responsible for: reabsorption of sodium, secretion of potassium, and the secretion of protons.
Pregnenolone Research
Enhances Cognition (13,14)
24-month-old rats were injected daily with either a placebo, .5mg/kg, or 2mg/kg of pregnenolone. Western blot analysis was used to determine the level of choline acetyltransferase (ChAT), a transferase enzyme responsible for the synthesis of acetylcholine (the primary neurotransmitter for memory and learning) and synaptic protein 1 (SYP1), which integral for neural function and synaptic signaling.
The results showed that 2.0mg/kg of pregnenolone significantly increased the levels of ChAT and SYP1 in the frontal lobe, temporal lobe, and hippocampus regions. At the same time, pregnenolone supplementation showed a decrease in acetylcholinesterase, which is responsible for breaking down acetylcholine.
Another randomized, placebo-controlled, double-blind study was conducted on 21 volunteers. The volunteers administered pregnenolone were done so at a dose of 500mg per day for eight weeks. Cognition was measured using The Brief Assessment of Cognition (BAC). While there was an increase in BAC scores, it was not deemed to be statistically significant. However, increases in allopregnanolone, a pregnenolone metabolite, predicted improvements in BAC composite scores at eight weeks. This suggests that peripheral pregnenolone levels may produce a significant response.
Improves Mood (15,16)
A proof-of-concept investigation was performed to determine pregnenolone’s effect on mood. 70 patients were randomly assigned to receive 100mg of pregnenolone or a placebo daily for eight weeks. Their mood was measured utilizing the Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scale (YMRS) on a bi-weekly basis. The group that received pregnenolone showed improvement in both the HRSD and YMRS.
A separate study using the HRSD and YMRS was conducted on 80 adults with a reported depressed mood state. In this study, they were assigned either a placebo or 500mg or pregnenolone daily for 12 weeks. It was again found that pregnenolone supplementation improved mood via both models with at least 61% of participants reporting an improved mood.
Stimulates Deep Sleep (17)
Paradoxical sleep (REM sleep) is the deepest stage of sleep. It is notable characterized by an abundance of acetylcholine. Cholinergic neurons of the pedunculopontine tegmentum nucleus (PPT) are important for initiating paradoxical sleep. Pregnenolone sulfate, a metabolite of pregnenolone, has synthesis enzymes that are present in this area. Both low (5ng) and high (10-20ng) of pregnenolone sulfate demonstrated they are able to increase the amount of paradoxical sleep.
Reduces Anxiety (18)
Allopregnanolone modulates the GABAᴀ to produce anxiolytic properties. Since pregnenolone increases levels of allopregnanolone, a study was conducted to determine pregnenolone’s impact on anxiety. 16 volunteers were administered 400mg of pregnenolone while 15 were given a placebo. To probe emotional processes, they were tasked with performing the Shifted-Attention Emotion Appraisal Task (SEAT) under a high-resolution MRI to measure neurocircuitry.
Allopregnanolone lead to reduced activity in the amygdala and insula across all conditions whereas the placebo did not. These regions are associated with generation of negative emotion. Allopregnanolone, via pregnenolone supplementation, demonstrate the ability to reduce anxiety.
Balances Immune System (19)
T helper 2 cells (Th2) regulate immunity by secreting various cytokines. Pregnenolone was demonstrated to by produced by Th2 cells in vitro and in vivo. The analysis suggests that the synthesis of pregnenolone in Th2 cells is related to immunosuppression. Pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching, which supports the suggestion of immunosuppression. This de novo production of pregnenolone may be an intrinsic situation of Th2-mediated immune responses to restore immune homeostasis.
Pregnenolone FAQ
Can pregnenolone help you to lose weight?
Although not commonly considered a benefit of pregnenolone, some hormones can boost your metabolism and weight loss may be a biproduct of that.
Can you take pregnenolone with DHEA?
It is not recommended to take pregnenolone with DHEA or any other hormonal supplement.
What causes low levels of pregnenolone in the body?
Pregnenolone levels generally decrease with age as a result of chronic stress. Inflammation and the transition to menopause are also causes of low levels of pregnenolone.
What is pregnenolone steal?
Pregnenolone steal is a condition where your body converts pregnenolone to cortisol instead of sex hormones.
What are symptoms of low pregnenolone levels?
Symptoms commonly associated with low levels of pregnenolone include; irritability, depression, anxiety, migraines, insomnia, or fatigue. However, these symptoms may be related to a myriad of health issues and therefore it should not be assumed its due to low pregnenolone.
How can I check how much pregnenolone I have?
You can get a blood test to see how much pregnenolone is in your body.
Do you need a prescription for pregnenolone?
Pregnenolone is sold as a dietary supplement in the United States that you do not need a prescription for. This may vary in other countries so should be checked prior to attempting to purchase pregnenolone.
Cited Sources
- https://www.ncbi.nlm.nih.gov/pubmed/15415436
- https://pubchem.ncbi.nlm.nih.gov/compound/8955#section=Pharmacology
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386997/
- https://hcahealthcare.com/hl/?/21848/Pregnenolone
- https://www.huffpost.com/entry/pregnenolone_b_1631742
- https://www.ncbi.nlm.nih.gov/pubmed/25030803
- Jong Rho; Raman Sankar; Carl E. Stafstrom (18 June 2010), page 479
- https://www.ncbi.nlm.nih.gov/pubmed/26844377
- https://www.ncbi.nlm.nih.gov/books/NBK9932/#_A1831_
- https://www.ncbi.nlm.nih.gov/books/NBK26910/
- https://www.sciencedirect.com/science/article/pii/0095852265900668
- https://www.news-medical.net/health/Dopamine-Functions.aspx
- https://www.ncbi.nlm.nih.gov/pubmed/23848990
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427920/
- https://www.ncbi.nlm.nih.gov/pubmed/20493557
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200497/
- https://www.ncbi.nlm.nih.gov/pubmed/15139033
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- https://chem.nlm.nih.gov/chemidplus/sid/0000145131
