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Pregnenolone is an endogenous steroid hormone produced primarily in the adrenal glands and brain. It is considered the “mother of all hormones” because it is directly derived from cholesterol and is the precursor to all steroid hormones including DHEA, testosterone, and progesterone. Adequate pregnenolone is necessary for a proper hormonal response, stress management, cognitive health, and efficient metabolism.
Pregnenolone is a youth-associated hormone because it is found in high concentrations in young people and levels naturally decrease with age. It is estimated that levels peak around age 30 and continue to decrease by around 60%. Pregnenolone can be converted to protective hormones which can decrease the impact of stress. This may explain its role in anti-aging because, with age, comes greater insults on the body such as toxin exposure, nutrient depletion, increased production of stress hormones, etc. In men, pregnenolone can be converted to DHEA and testosterone, both which have been demonstrated to offset the damaging effects of excess cortisol, estrogen, and neurodegeneration. Supplementing pregnenolone may help maintain healthy hormone levels in the body, decrease the impact of stress, and support brain health.
Anti-Aging Benefits
Pregnenolone is converted from cholesterol to DHEA, the precursor to testosterone, in the adrenal glands, testes, and brain. Although its mechanisms are still being researched, DHEA is also a youth-associated hormone because of its anti-cortisol actions and role in sugar and fat metabolism. DHEA has been demonstrated to promote energy production by supporting enzymes needed for the cellular uptake of nutrients and promoting a healthy insulin response, which both play a role in a healthy metabolism and weight management. It also opposes the harmful effects of excess stress hormones, which can potentially lead to such things as high blood sugar, hypertension, and bone tissue breakdown. DHEA counters these effects by increasing bone mineral density, promoting insulin sensitivity, and regulating blood pressure.
DHEA can further metabolize into testosterone, which similarly decreases with age. Testosterone is critical for healthy cardiovascular and sexual function, protection against estrogens, and healthy thyroid function. Supplementing with DHEA increases testosterone levels at higher, more concentrated rates. However, pregnenolone enhances the production of testosterone by supporting the optimal function of the entire endocrine system. This suggests that pregnenolone may be a safer option for those in need of additional hormonal support.
Studies demonstrate that pregnenolone also helps with elevated blood cholesterol by returning steroid levels to optimal proportions. These hormones (DHEA, testosterone, estrogen, and progesterone) play a role in regulating the body’s production of cholesterol. Pregnenolone has shown other cardioprotective qualities as well because of its antioxidant and antiapoptotic properties, along with its role in supporting a healthy inflammatory response.
Pregnenolone & the Body’s Stress Response
Aging often causes alterations to the hypothalamic-pituitary-adrenal (HPA) axis, which is responsible for regulating the body’s response to cortisol, a primary stress hormone. Cortisol levels typically increase especially around age 60 which coincides with decreasing levels of other steroid hormones. Increased blood cortisol coupled with decreasing pregnenolone, DHEA, and testosterone can contribute to negative symptoms. Most notable is excess cortisol’s ability to alter insulin response, promote weight gain, increase blood pressure, and break down muscle and bone tissue. Pregnenolone, through its conversion to DHEA as previously mentioned, blocks the negative actions of cortisol. A study that measured serum cortisol levels following DHEA administration for 30 days “resulted in a decrease in plasma cortisol concentrations.” Another study exploring the relationship between metabolic syndrome, cortisol, and DHEA found that individuals with impaired metabolic response experienced both increased cortisol and DHEA. The authors found that the body naturally raises DHEA when cortisol is high as a protective mechanism. Adequate pregnenolone is required for DHEA production in adrenal glands.
Pregnenolone may also be metabolized into allopregnanolone, a neurosteroid known for its neuroprotective and anti-anxiety effects. Allopregnanolone binds to the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), which plays a role in regulating the central nervous system, producing a calming effect. In a study where subjects were administered 400 mg of pregnenolone, “reduced activity in the amygdala (the fear center of the brain)…and enhance[d] activity in regions of the brain linked to regulatory processes” were reported. It is noted that chronic stress exposure alters the responsivity of the HPA axis and decreases allopregnanolone levels. Maintaining pregnenolone levels may effectively inhibit the HPA axis and help with the body’s stress response by regulating allopregnanolone.
Pregnenolone & Brain Health
The body’s most important organ, the brain, naturally contains a high concentration of pregnenolone, suggesting its protective effects. Various studies demonstrate that the steroid helps support mood and cognition, and promotes restful sleep. A study published in Neuropsychopharmacology found that administration of pregnenolone in patients with bipolar depressive disorder resulted in 61% depression remission. Another study in Brain Research found that pregnenolone supplementation in men increased the amount of time subjects spent in slow-wave sleep (deep sleep). Slow-wave sleep helps support normal tissue repair, immune function, and clear thinking.
Researchers have concluded that “a decreased level of pregnenolone has been observed in neuroinflammatory diseases. When restored to optimal levels, pregnenolone protects the brain from toxins and may even help to regulate disorders associated with stress and drug use. It promotes myelination in neurons, which allows the central nervous system to conduct impulses more efficiently. Metabolic disorders are similarly associated with decreased cognition and memory. Pregnenolone has shown to be a therapeutic agent in metabolic dysfunction by supporting memory and brain function, specifically by regulating acetylcholine which helps brain cells communicate with one another.
Pregnenolone Supplementation
Pregnenolone has countless beneficial properties that are associated with hormone balance, healthy cognition, and the body’s response to stress. Because each individual has their own hormonal makeup, blood hormone testing may provide insight into proper dosages for pregnenolone supplementation.
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