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Home > Anti-aging Research > Cortisol.

Cortisol

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Note:  To lower cortisol, I feel the best way to go is phosphatidylserine (PS), Remeron (mirtazapine) and/or Avandia (rosiglitazone) although there is only one study on mice that I know of with Avandia.  An effective PS dose of 800 mg per day lowered cortisol in one study by 30%.  However that amount runs about $6 per day.  See my dedicated page on the only study I've seen regarding Remeron (an antidepressant).  Click here for articles on Avandia.  Remeron and Avandia are available through OffshoreRX.combut check with a doctor before taking any supplement or medication.  Avandia is also available through SuperSaverMeds.com.

A new product, Relora at 750 mg/day has been shown to reduce cortisol by 37%.  See Vitamin Shoppe.  For phosphatidylserine, see Vitacosticon, iHerb and Vitamin Shoppe.  I tried Relora and didn't at all like the way it made me feel.  CortiSlim is also available at Vitamin Shoppe or drugstore.comicon.  Also,  Relacoreicon at drugstore.com and Cortisol formulas at iHerb.  I feel these formulas may be designed my the accountant though.

I was watching Dr. Perricone anti-aging lectures on PBS in late August 2002 and he claims that DHEA can help protect the brain from the negative effects of cortisol.  I take 50 mg/day of the 7-keto DHEA.

I was updating the links and noticed that several of the links below went dead but left them anyway because of the quote. - Ben

Popular Supplements thought to Reduce Cortisol:

Medications that may reduce cortisol:

The important news:

  • The relationship of serum and salivary cortisol levels to male sexual dysfunction as measured by the International Index of Erectile Function - Int J Impot Res. 2009 May 7 - "testosterone (T) and cortisol (F) ... (Total-T, Free-T, Bioavailable-T, Total-F and Bioavailable-F) and salivary hormones (Saliva-T and Saliva-F) ... International Index of Erectile Function (IIEF) ... Free-T and Bioavailable-T showed significant inverse correlations with age (P<0.01). In the group not taking antidepressants, the levels of Bioavailable-F and Saliva-F showed significant inverse correlations with a portion of the IIEF score (P<0.05). However, reductions in Bioavailable-T and Saliva-T showed no association with the IIEF score. In the group taking antidepressants, these hormone levels showed no correlation with IIEF"
  • Effects of phosphatidylserine supplementation on exercising humans - Sports Med. 2006;36(8):657-69 - "S-PtdSer 800 mg/day reduced the cortisol response to overtraining during weight training while improving feeling of well-being and decreasing perceived muscle soreness"
  • Associations of salivary cortisol with cognitive function in the Baltimore memory study - Arch Gen Psychiatry. 2007 Jul;64(7):810-8 - "Higher levels of pretest and mean cortisol as well as the area under the curve of cortisol over the study visit were associated with worse performance (P < .05) in 6 domains (language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, and visual memory). For instance, an interquartile range increase in the area under the curve was equivalent to a decrease in the language score expected from an increase in 5.6 (95% confidence interval, 4.2-7.1) years of age"
  • Chronic Exposure To Stress Hormone Causes Anxious Behavior In Mice - Science Daily, 4/17/06 - "Scientists already knew that many people with depression have high levels of cortisol, a human stress hormone, but it wasn't clear whether that was a cause or effect. Now it appears likely that long-term exposure to cortisol actually contributes to the symptoms of depression"
  • Pharmacologic management of Cushing syndrome : new targets for therapy - Treat Endocrinol. 2005;4(2):87-94 - "Compounds with neuromodulatory properties have been effective in only a limited number of cases of hypothalamic-pituitary-dependent Cushing disease, the most common form of Cushing syndrome. These agents include serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), GABA agonists (valproic acid [sodium valproate]), and somatostatin analogs (octreotide). Interesting new avenues at the pituitary level involve the potential use of thiazolidinedione compounds, such as rosiglitazone, and of retinoic acid, which are ligands of different nuclear hormone receptors involved in hypothalamic-pituitary regulation"
  • Diabetes Drugs May Help Cushing's Syndrome - Reuters Wire, 11/07/2002 - "Cushing's syndrome results from high levels of the hormone cortisol, and can cause fat accumulation in the upper body and face, and thinning of the arms and legs. Patients can experience high blood pressure and high blood sugar, along with depression, fatigue, irritability and weakened bones ... a protein called PPAR-gamma, which is found on pituitary gland tumor cells, appears to be linked to overproduction of ACTH ... researchers injected mice with ACTH-secreting pituitary tumor cells and then treated them with commonly used diabetes drugs, rosiglitazone (Avandia) and troglitazone, or an inactive placebo ... There was an 85% reduction in ACTH and a corresponding 96% reduction in their cortisol-like hormone"
  • Mirtazapine Regulates Stress Hormones, Improves Sleep In Depressed Patients - Doctor's Guide, 8/8/01 - "Mirtazipine might be the best option for depressed patients with sleep disturbance and irregularities in stress hormone function ... Depression is often accompanied by sleep disturbance -- subjective and objective -- as well as [hypothalamic-pituitary-adrenal] HPA-axis dysregulation ... Mirtazapine is a treatment that [profoundly affects] the HPA-axis within hours and promotes sleep within days ... They tested the 24-hour urinary free cortisol (UFC) levels of 16 healthy men and 20 men and women with major depression ... mirtazipne significantly reduced UFC concentrations, which is often elevated in depressed patients"
  • Cortisol - Keeping a Dangerous Hormone in Check - Life Extension Magazine, 7/04 - "daily cortisol production increased by 54% from a group of 21- to 30-year-old men to a group of men over 70 ... Phosphatidylserine, DHEA, and ginkgo biloba all have been shown to reduce the amount of cortisol produced during stressful events, and these stress fighters can help retard the negative consequences of this hormone" - See iHerb or Vitacosticon phosphatidylserine products.
  • The Role of Cortisol and Depression: Exploring New Opportunities for Treatments - Psychiatric Times, 5/04 - "Although glucocorticoid production is essential for survival, overproduction is associated with a significant disruption of cellular functioning, which, in turn, leads to widespread physiological dysfunction ... Cortisol, a glucocorticoid released from the adrenal cortex, is the end product of the HPA axis ... The physiological function of DHEA and its sulphated metabolite (DHEA-S) is unclear, but these circulating corticosteroids have been shown to possess antiglucocorticoid properties, and high cortisol/DHEA ratios are reported to be associated with persistent depression"
  • Why Are So Many Women Depressed? - Scientific America Women's Health: A Life Long Guide, Summer 1998 (see the subtopic "Stress and Cortisol") - "It is unclear whether depression is a cause or a consequence of elevated cortisol levels, but the two are undoubtedly related."
  • Wilson's Reverse T3 Dominance Syndrome - knoxintegrativemed.com - "However, when a person experiences prolonged stress, the adrenal glands respond by manufacturing a large amount of cortisol. Cortisol inhibits the conversion of T4 to T3 and favors the conversion of T4 to RT3. If stress is prolonged, a condition called Reverse T3 Dominance occurs and persists even after the stress passes and cortisol levels fall. Apparently, RT3 itself acts like cortisol and blocks the conversion of T4 to T3"
  • Wilson's Syndrome - providentmedical.com - "We know that elevated amounts of cortisol, the major stress hormone, can block 5 prime deiodinase, keeping T4 from being converted to T3.  This results in most of the T4 being converted into reverse T3, which then needs the available 5 prime deiodinase to be converted into T2."
  • Low-Dose DHEA Increases Androgen, Estrogen Levels in Menopause - Medscape, 12/12/03 - "Cortisol F plasma levels progressively decreased throughout the study." - See iHerbor Vitacosticon DHEA products.
  • A diet fortified with L-lysine and L-arginine reduces plasma cortisol and blocks anxiogenic response to transportation in pigs - Nutr Neurosci. 2003 Oct;6(5):283-9
  • Fish oil prevents the adrenal activation elicited by mental stress in healthy men - Diabetes Metab. 2003 Jun;29(3):289-295 - "In control conditions, mental stress significantly increased heart rate, mean blood pressure, and energy expenditure. It increased plasma epinephrine from 60.9 +/- 6.2 to 89.3 +/- 16.1 pg/ml (p<0.05), plasma cortisol from 291 +/- 32 to 372 +/- 37 micromol/l ... After 3 weeks of a diet supplemented with n-3 fatty acids, the stimulation by mental stress of plasma epinephrine, cortisol, energy expenditure, and plasma non esterified fatty acids concentrations, were all significantly blunted ... Supplementation with n-3 fatty acids inhibits the adrenal activation elicited by a mental stress" - See Mega Twin EPA at Vitacosticon or iHerb.
  • Disappointing Data Confound Claims For DHEA Effectiveness [against Alzheimer's] - Psychiatric News, 6/6/03 - "DHEA has been reported to reduce cortisol, the so-called "stress hormone," which in response to stress is released in large quantities that have been linked to neuronal stress and damage" -  Does anyone detect bias in that title?  I don't know if DHEA helps Alzheimer's or not but I feel the title should have been something like "Alzheimer's Shows Trend Toward Improvement with DHEA at 3 Months".  Their attitude seems to be that nothing works except what we write prescriptions for.  The way I understand it, Alzheimer's usually gets worse, not better and cholinesterase inhibitors slow the disease, they don't reverse it and three months is a short time to determine if it is working.  For example, see the following  in the same issue of Clinical Psychiatry News.  See iHerb or Vitacosticon DHEA products. - Ben
  • Light Sleeper, Heavy Gainer - HealthDay, 2/14/03 - "Sleep deprivation can increase production of cortisol, a stress hormone that stimulates the appetite"
  • Stress, Cortisol and Health - Supplement Watch Newsletter, 10/02 - "several lines of evidence have converged to solidify the concept that stress makes us fat (because of cortisol), thins our bones (because of cortisol), shrinks our brains (because of cortisol), suppresses our immune system (because of cortisol), saps our energy levels (because of cortisol), and kills our sex drive (because of cortisol) ... Take a daily multivitamin/multi-mineral supplement - because calcium, magnesium, vitamin C and B-complex vitamins are needed for a proper stress response ... Chief among the supplements with documented cortisol-controlling effects are Phosphatidylserine, Beta-sitosterol, Magnolia bark, Theanine, Epimedium, Ashwagandha and Passionflower"
  • Phosphatidylserine (PS) The Essential Brain Nutrient - Life Extension Magazine, 9/02 - "Among its list of functions, phosphatidylserine stimulates the release of dopamine (a mood regulator that also control physical sensations, and movement), increases the production of acetylcholine (necessary for learning and memory), enhances brain glucose metabolism (the fuel used for brain activity), reduces cortisol levels (a stress hormone), and boosts the activity of nerve growth factor (NGF), which oversees the health of cholinergic neurons"
  • A Supplement to Prevent Alzheimer’s - Dr. Weil, 8/20/02 - "In theory, PS works by strengthening cell membranes thus protecting them and their contents from damage, particularly from the stress hormone cortisol"
  • Testosterone Deficiency & Depression, Does DHEA Raise the Levels of Bioavailable Testosterone in Men? - Life Extension Magazine, 8/02 - "We know that as cortisol rises, testosterone levels tend to drop"
  • Hypercortisolemia Cited in Link Between Depression and Cardiovascular Disorders - Doctor's Guide, 4/9/02 - "Depressed patients who are also hypercortisolemic appear to have resistance to insulin and increased visceral fat, possibly accounting for a link between major depression and cardiovascular disorders"
  • Physical and Psychological Effects of Stress - MedicineNet.com, 2/02 - "Under excessive stress, we tend to produce cortisol, the classic anti-stress hormone produced by our body, perhaps to conserve energy. However the side-effect here is sexual dysfunction and infertility as cortisol also inhibits production of the hormones essential for sexual"
  • Errant Enzyme Causes Big Bellies - WebMD, 12/11/01 - "They looked at an enzyme called 11-beta hydroxysteroid dehydrogenase type 1. This enzyme is able to increase the level of cortisol in fat cells without raising the level of cortisol in the blood"
  • Single enzyme to blame for potbellies: study - MSNBC, 12/6/01 - "What they found was that a single enzyme in fat cells that raises levels of cortisol — the “fight or flight” stress hormone — triggers fat accumulation around the belly and its associated ill effects ... The researchers were drawn to the role of cortisol because patients with a rare illness known as Cushing syndrome — who have too much of the steroid hormone in their blood — develop severe obesity concentrated around their middles and become diabetic ... Since overweight people without Cushing syndrome typically don’t have too much cortisol in their bloodstreams, Flier hypothesized that they may be producing high cortisol levels solely in their fat cells — possibly because the enzyme HSD-1, which makes cortisol from an inactive molecule, is overactive ... The level of cortisol in their stomach fat tissue was 15 percent to 30 percent higher than in their non-engineered counterparts" - Note: The way I read this article, the final culprit is still the cortisol and there are ways to reduce cortisol now.
  • Retinoic acid prevents experimental Cushing syndrome - J Clin Invest, October 2001, Volume 108, Number 8, 1123-1131 - "This glucocorticoid excess produces abnormal fat deposition, adrenal hyperplasia, thinning of the skin, hypertension, and psychological disturbances"
  • Sleep Deprivation May Trigger Insulin Resistance - Clinical Psychiatry News, 10/01 - "sleep deprivation leads to the release of tumor necrosis factor-, which triggers cortisol release, and that, in turn, causes insulin resistance"
  • Researchers Explore New Meds for Mood Disorders - Clinical Psychiatry News, 10/01 - "Another approach being developed for patients with high levels of circulating cortisol involves the abortion pill mifepristone ... The findings, to be published this month in the Journal of Clinical Psychopharmacology, suggest that a rapid antidepressant response (approximately 7 days) may occur in some patients"
  • Researchers Hopeful Antidepressant Augmentation Will Improve Remission - Clinical Psychiatry News, 9/01 - "In psychotic depression, a corticosteroid antagonist looks most promising. Mifepristone, which is used to induce abortions but was originally designed as treatment for Cushing's disease, has achieved rapid reversal of symptoms in some 30 psychotically depressed patients, ostensibly by blocking cortisol receptors. The drug is now being investigated in a large double-blind trial, he said"
  • Two studies implying that cortisol is the cause, not the result of depression:
  • Procaine HCI - aidsmap.com, 6/28/01
  • AACE Clinical Practice Guidelines For The Evaluation and Treatment of Male Sexual Dysfunction - American Association of Clinical Endocrinologists - "Other endocrine disorders that may cause libido or erectile difficulties include hypothyroidism, hyperthyroidism, adrenal insufficiency, or excessive levels of adrenal corticosteroids [cortisol]"
  • How You React to Stress May Affect How Your Clothes Fit - WebMD, 1/16/01 - "fat created by cortisol is the "deep-belly" kind, which, one expert says, is known to increase health risks"
  • RU-486 could aid variety of ills - MSNBC, 11/2/00 - "RU-486's ability to block the action of a different hormone � cortisol � has prompted doctors to try it for psychotic depression. In addition to feeling sad and worthless, people with this devastating condition have distorted thinking and often suffer delusions or hallucinations. Many
    become suicidal.

    They have very, very disturbing and crazy thoughts ... and they have no ability to suppress them,� said Joseph K. Belanoff, a California psychiatrist who is chief executive officer of Corcept Therapeutics Inc., a small pharmaceutical company. Corcept is sponsoring a study of RU-486 for psychotic depression.

    Several lines of evidence have led researchers to suspect that some of the symptoms of psychotic depression are caused by an excess of cortisol in the brain. Cortisol levels rise in response to stress and may be abnormally elevated in depressed individuals. Similar symptoms can occur in patients with Cushing's syndrome, an overabundance of cortisol usually caused by a tumor, and RU-486 has cured the mental disturbance in some
    such cases.

    Our feeling has been that a lot of the cognitive problems and delusions that you see in some of the patients are due to the [cortisol],� said Alan F. Schatzberg, chairman of the psychiatry department at Stanford University School of Medicine, where researchers are conducting a study that will test RU-486 on 30 patients with psychotic depression.

    RU-486 or other cortisol-blocking drugs �may be better alternatives than ... some of the typical treatments� such as antipsychotic drugs or electric shock therapy, he said."
  • Neuroscience finds foggy link between depression and memory loss - CNN, 4/18/00 - "Studies show that prolonged depression or stress leads to elevated levels of cortisol, a "stress" hormone produced by the adrenal glands. This in turn appears to shrink or atrophy the hippocampus, the sea-horse shaped part of the brain associated with many kinds of memory and learning."
  • STGI Announces Anticort's FDA Phase I/II is Moving Forward - aegis.com, 7/28/99 - "Procaine (the active ingredient of Anticort(TM)) has been used clinically for more than 40 years, primarily as the local injectable anesthetic Novocaine. Despite the widespread use of procaine, reports of side effects have been rare, and are usually associated with excessive dosage, rapid absorption or inadvertent intravascular injection ... For the pharmacokinetics study, participants will receive Anticort(TM) at a single oral dose of 200 mg (cohort A), 400 mg (cohort B), 600 mg (cohort C) or 800 mg (cohort D). For the 8-week continuous dosing study, participants will receive 200 mg (1 pill per day; cohort A), 400 mg (1 pill twice daily; cohort B), 600 mg (1 pill three times daily; cohort C) or 800 mg (2 pills twice daily; cohort D). To ensure the safety of each dose level, these cohorts will be enrolled sequentially"
  • Study Supports Role Of Anticort In Treating Alzheimer's, HIV - Doctor's Guide, 4/17/98 - "Cortisol's role as a cause of disease is most recently confirmed in a study to be published in the May issue of the journal Nature Neuroscience. Authored by Dr. Sonia Lupien of McGill University, the study reports that high levels of cortisol play a key role in Alzheimer's, memory loss, shrinkage of the brain and aging. Dr. Lupien also states that such illnesses might be prevented with medications to reduce elevated cortisol levels."
  • Georgetown Researchers Report Development of New Way to Control Excess Cortisol Levels - Georgetown University Medical Center, 6/12/00 - "Although more work is needed to understand how Anticort works, these results clearly indicate that we now have a powerful tool to control the stress response and its detrimental effects on the body"
  • Endocrinology of Aging - Medscape, 3/00 - "Excessive lifelong adrenal cortisol feedback on the brain may exacerbate the aging-associated loss in neuronal synapses and plasticity"
  • Hypericum, Drug Interatcions, and Liver Effects  - MedHerb.com, 2/00 - "Endogenous hormones metabolized by the CYP3A enzyme system - estradiol, estriol, testosterone, cortisol"
  • The Neurobiology of Depression - Scientific America, 6/98 - "When a threat to physical or psychological well-being is detected, the hypothalamus amplifies production of corticotropin-releasing factor (CRF), which induces the pituitary to secrete ACTH. ACTH then instructs the adrenal gland atop each kidney to release cortisol"
  • Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides - Alzheimer Dis Assoc Disord 1995 Fall;9(3):128-31 - "beta-endorphins significantly decreased after treatment; plasma cortisol levels matched this reduction. Since both CSF beta-endorphins and plasma cortisol decreased, one possible explanation is that ALCAR reduced the AD-dependent hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity"
  • Adrenal Disease - Life Extension Magazine
  • Anxiety and Stress - Life Extension Magazine
  • About Relora - Relora.com
  • Psychotic Depression - healthyplace.com - "Researchers aren't exactly sure what causes major depressive disorder with psychotic features (psychotic depression), but it's frequently associated with high levels in the blood of a hormone called cortisol"
  • Gerovital GH-3 information - International Antiaging Systems - "It is also known that Gerovital-H3 can help reduce cortisol levels, the hormone responsible for stress and a rare hormone in that it is one of the few that increases with age. It is believed that high-cortisol levels lead to accelerated aging because cortisol “attacks” the hypothalamus, the area of the brain that “controls” the endocrine system. Ironically cortisol may run out-of-control due to its ability to damage the hypothalamus that controls the adrenal glands that produce cortisol!" - Note:  I'm not a doctor but the way I understand it, GH-3 (procaine HCl) reduces 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity.  This is what statins do to lower cholesterol.  Cortisol is made from cholesterol therefore less cholesterol equals less cortisol.  The company making Anticort (procaine HCl), stopped after phase II studies.  See J Pharmacol Exp Ther. 2003 Dec;307(3):1148-57. Epub 2003 Oct 14.  - Ben

Effects of cortisol on thyroid:

  • central hypothyroidism---fibromyalgia, hypothyroidism, thyroid hormone resistance - drlowe.com - "During stress (such as surgery or an auto accident), the adrenal glands increase their secretion of cortisol. The increase in cortisol inhibits the thyroid system in two ways: (1) it decreases TSH secretion by the pituitary gland, and (2) it decreases conversion of T4 to T3"
  • Wilson's Reverse T3 Dominance Syndrome - knoxintegrativemed.com - "However, when a person experiences prolonged stress, the adrenal glands respond by manufacturing a large amount of cortisol. Cortisol inhibits the conversion of T4 to T3 and favors the conversion of T4 to RT3. If stress is prolonged, a condition called Reverse T3 Dominance occurs and persists even after the stress passes and cortisol levels fall. Apparently, RT3 itself acts like cortisol and blocks the conversion of T4 to T3"
  • Wilson's Syndrome - providentmedical.com - "We know that elevated amounts of cortisol, the major stress hormone, can block 5 prime deiodinase, keeping T4 from being converted to T3.  This results in most of the T4 being converted into reverse T3, which then needs the available 5 prime deiodinase to be converted into T2."
  • Wilson's Thyroid Syndrome - "Conversion of T4 to T3 can also be impaired by glucocorticoids" - Maybe that is the mechanism by which cortisol causes depression, and if so, could T3 then cure the depression? - Ben, Related article:
  • Use OF T3 Thyroid Hormone to Treat Depression - DrMirkin.com, 5/11/01 - "some people become depressed when they take just T4 and their depression can be cured when they take both thyroid hormones, T3 and T4"

Alternative News:

CME:

General Information:

Other News:


Cushing's syndrome is caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. I've talked to doctors who implied that it was black and white, i.e. you have Cushing's or you don't.  My personal opinion, and I'm not a doctor, is that there is a linear gray area in between.

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