Pregnenolone as a therapeutic supplement
Pregnenolone is a naturally occurring steroid hormone synthesized in the body from cholesterol, often referred to as the "grandmother of all steroid hormones" due to its role as a precursor for other key hormones like testosterone and estrogen. As a therapeutic supplement, it has been proposed for various health issues, including aging, Alzheimer's disease, depression, and menopausal symptoms, among others. It is important to note that while pregnenolone levels do not decline with age, some believe that supplementing it may help maintain youthful hormone levels.
Recent research has suggested potential benefits of pregnenolone in enhancing cognitive function and alleviating mood disorders, particularly in patients with bipolar disorder and schizophrenia. However, the long-term effects of pregnenolone supplementation are not well understood, and experts caution against its use until more is known. Pregnenolone is legally classified as a dietary supplement but functions similarly to a drug, necessitating careful consideration and consultation with a healthcare provider before use. Side effects can include gastrointestinal upset, hair loss, and mood swings, among others. Pregnenolone should be approached with caution, particularly for individuals with hormone-sensitive conditions or those taking specific medications.
Pregnenolone as a therapeutic supplement
- PRINCIPAL PROPOSED USES: None
- OTHER PROPOSED USES: Aging in general, Alzheimer’s disease, depression, enhancing memory and mental function, fatigue, menopausal symptoms, osteoporosis, Parkinson’s disease, rheumatoid arthritis, stress, weight loss
DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.
Overview
Pregnenolone has been called the grandmother of all steroid hormones. The body manufactures it from cholesterol and then uses it to make testosterone, cortisone, progesterone, estrogen, DHEA (5-dehydroepiandrosterone), androstenedione, aldosterone, and all other hormones in the steroid family.
One reason given for using pregnenolone is that the level of many of these hormones declines with age. By taking pregnenolone supplements, proponents say, people can keep all their hormones at youthful levels. However, pregnenolone levels themselves do not decline with age, and there is no indication that taking extra pregnenolone will increase the levels of any other hormones.
Steroid hormones are powerful substances, and they can cause harm as well as benefit. Long-term use of cortisone causes severe osteoporosis. Estrogen can increase the risk of cancer, and anabolic steroidsused by athletesmay cause liver problems and stress the heart. Experts have very little idea what long-term consequences the use of pregnenolone might entail.
Pregnenolone is legally classified as a dietary supplement, but it is not a nutrient. It is a drug, just as estrogen, cortisone, and aldosterone are drugs. Its use is not recommended until scientists know more about what it really does.
Before research on pregnenolone expanded in the twenty-first century, there had been only one effect of pregnenolone that had been documented via double-blind, placebo-controlled studies: for reasons that are not clear, regular use of pregnenolone may greatly decrease the sedative effect of drugs in the Valium family (benzodiazepines).
Requirements and Sources
Pregnenolone is not normally obtained from foods. The human body manufactures it from cholesterol. Supplemental pregnenolone is made synthetically in a lab from substances found in soybeans.
Therapeutic Dosages
A typical recommended dosage of pregnenolone is between 30 and 250 milligrams (mg) daily, but some studies have used as much as 700 mg. Research indicates it is safe for use for up to twelve weeks.
Therapeutic Uses
On the Internet and in health magazines, pregnenolone is described as a treatment for an enormous list of health problems, including Alzheimer’s disease, menopausal symptoms, Parkinson’s disease, osteoporosis, fatigue, stress, depression, and rheumatoid arthritis. It is also supposed to help people lose weight, improve brain power, and make people feel young again. However, like many supplements, there was little to no scientific evidence for any of these uses until research expanded in the twenty-first century.
In the late 2010s and early 2020s, research expanded on the therapeutic uses of pregnenolone. Human studies indicated it may improve memory and facilitate learning. Researchers reported that pregnenolone showed promise in brain-based health benefits related to increasing cognitive function. Its neuroprotective qualities were believed to offer hope for research into Alzheimer's. Pregnenolone was also studied for its mental health benefits. A small study showed pregnenolone eased depression symptoms in patients with bipolar disorder, and other studies showed it to alleviate symptoms of schizophrenia. Supplementing with pregnenolone was also shown to be effective in treating patients with alcohol and cocaine use disorders.
Neurosteroids like pregnenolone gained an increased importance in twenty-first-century biomedical research in understanding and treating neurodegenerative diseases and mood disorders. In 2019, the US Food and Drug Administration approved the first neurosteroid drug called brexanolone, intended to treat postpartum depression. As the potential use of these steroids for medicinal purposes increased, funding for research also increased. Researchers discovered that, generally, pregnenolone levels were elevated in individuals with Alzheimer's disease but low in individuals with major depression and bipolar disorder. Because neurosteroids regulate nervous system function, their role in mental wellness and neurological aging may be more important than previously believed. Their potential to treat these conditions is uncertain, but some research is positive. For example, some research found positive results in treating traumatic brain injury (TBI) with pregnenolone because of its neuroregeneration properties.
Safety Issues
Pregnenolone is a powerful hormone, not a nutrient that people naturally get in their food. This supplement should be approached with caution, as if it were a drug because it behaves like a drug. Individuals considering taking a pregnenolone supplement should consult a doctor first to ensure it is safe to use with specific medications or conditions. Pregnenolone is not recommended for children, pregnant or nursing women, or those with liver or kidney disease. Pregnenolone is also not recommended for patients with hormone-sensitive conditions.
Potential side effects include gastrointestinal upset, hair loss, sweating, tremors, drowsiness, skin issues like rashes or acne, and mood swings like excitement or agitation.
Important Interactions
As noted earlier, pregnenolone may decrease the effectiveness of sedatives in the Valium family (benzodiazepines). People using benzodiazepine drugs for sleep or anxiety find that these drugs do not work as well if they take pregnenolone. Taking medications that contain estrogen, progesterone, progestin, or testosterone with pregnenolone may result in a hormonal imbalance or too much of these hormones in the body.
Bibliography
Flood, J. F., et al. “Pregnenolone Sulfate Enhances Post-training Memory Processes When Injected in Very Low Doses into Limbic System Structures: The Amygdala Is by Far the Most Sensitive.” Proceedings of the National Academy of Science USA, vol. 92, 1995, pp. 10806-10.
Kelly, Caitilin. “Pregnenolone: Benefits, Side Effects, Dosage, and Interactions.” Verywell Mind, 7 Feb. 2023, www.verywellmind.com/the-lowdown-on-pregnenolone-89502. Accessed 1 Oct. 2024.
Marx, Chris. "Traumatic Brain Injury and Psychological Health." Congressionally Directed Medical Research Programs, 29 Sept. 2023, cdmrp.health.mil/tbiphrp/research‗highlights/23Chris‗Marx‗highlight. Accessed 1 Oct. 2024.
Meieran, S. E., et al. “Chronic Pregnenolone Effects in Normal Humans: Attenuation of Benzodiazepine-Induced Sedation.” Psychoneuroendocrinology, vol. 29, 2004, pp. 486-500.
Murugan S., et al. “The Neurosteroid Pregnenolone Promotes Degradation of Key Proteins in the Innate Immune Signaling to Suppress Inflammation." Journal of Biological Chemistry, vol. 294, no. 12, 2019, pp. 4596-4607. doi:10.1074/jbc.RA118.005543.
Wampler, Susan. "New USC Mann Study Unlocks the Potential of Neurosteroids." USC Mann, University of Southern California, 28 Aug. 2023, mann.usc.edu/news/new-usc-mann-study-unlocks-the-potential-of-neurosteroids. Accessed 1 Oct. 2024.