24 replies to this topic

[lucid]

Cortisol is a hormone released indirectly in response to stress. When the adrenal gland releases adrenaline this triggers the release of the hormone called cortisol.

It increases blood pressure, blood sugar levels and has an immunosuppressive action. In pharmacology, the synthetic form of cortisol is referred to as hydrocortisone, and is used to treat allergies and inflammation as well as cortisol production defficiencies.

Recently I have seen some infomercials pushing an over the counter product called Relacore. This product apparently reduces cortisol. The active ingredient is magnolia bark which is compared to Valium as an anti anxiety drug.

Cortisol is shown to be very detrimental to health. Its cousin hormone used in the salmon species is the drug mass produced after some species mate; triggering programmed death. I believe that it has also been shown to induce heart disease in humans which partially explains how people die after experiencing trauma.

In this Study it is shown that CR delays onset of age related increases in cortisol.

Dietary caloric restriction (CR) slows aging, extends lifespan, and reduces the occurrence of age-related diseases in short-lived species. However, it is unclear whether CR can exert similar beneficial effects in long-lived species, like primates. Our objective was to determine if CR could attenuate purported age-related changes in the 24-h release of adrenal steroids. To this end, we examined 24-h plasma profiles of cortisol, and dehydroepiandrosterone sulfate (DHEAS) in young and old, male and female rhesus macaques (Macaca mulatta) subjected to either ad libitum (AL)-feeding or CR (70% of AL) for 2-4 years. Hormone profiles from young monkeys showed pronounced 24-h rhythms. Cortisol concentrations were higher in old males but not females, whereas DHEAS rhythms were dampened with age in both sexes. The cortisol rhythms of old CR males resembled those of young control males. However, CR failed to prevent age-related declines in DHEAS and further dampened DHEAS rhythms in both sexes. Apart from the partial attenuation of the age-related cortisol elevation in the old males, 24-h adrenal steroid rhythms did not benefit from late-onset CR.

Too low cortisol results in Attisons disease. I know some studies were done though where the adrenal gland was removed in mice, and doing so resulted in I believe longer life spans in mice exposed to stress. Ill read up on this again later and update the post.

Cortisol is very important to aging. As mentioned, It is one of the most important factors in programmed organism death. I was wondering what kind of knowledge that people here have of cortisol and cortisol level management. Cheers.

[Shepard]

Like insulin, I think people put too much emphasis on trying to minimize cortisol when they shouldn't. Chronically elevated cortisol is an entirely different beast than normal cortisol patterns throughout the day.

[lucid]

Well, cortisol patterns like many other hormone patterns, change unfavorably as we age. Something to consider...

[Shepard]

Well, cortisol patterns like many other hormone patterns, change unfavorably as we age. Something to consider...

True. I guess I was viewing this topic as more anti-aging than controlling an already unfavorable hormonal situation.

To what degree is cortisol going to be damaging in an aging person that has lived a healthy diet/lifestyle? Not so much, I imagine.

[biknut]

Gerovital H3 (GH3) is a proven Cortisol inhibitor. Relacore is not.

[krillin]

7-keto DHEA is the only anti-cortisol treatment that worked (past tense, unfortunately) for me, as rated by ability to relieve neck and shoulder tension from mold allergy. GH3, Holy Basil, Relora, Rhodiola, Ashwagandha, Eleuthero, and Panax Ginseng were total busts. I think the Panax actually made it worse. The GH3 and Rhodiola do give a mild high, though.

[biknut]

One thing I can say about GH3 is it's hard to take properly. It must be taken on a empty stomach and you can't eat anything for 45 minutes after. Also, another big problem with GH3 is a lot of brands are total fakes with no procaine hydrochloride at all in them.

The brand I buy is Romanian, Gerovital H3, made by S.A. Sicomed.

[Shepard]

7-keto DHEA is the only anti-cortisol treatment that worked (past tense, unfortunately) for me, as rated by ability to relieve neck and shoulder tension from mold allergy. 

Did you try higher doses of Vitamin C?

[zoolander]

what about stress reduction techniques? I'm betting a regular routine of mindful mediation and awareness training would trump any cortisol reducing medication/supplement for reducing cortisol overtime.

Can those who are stating that Gerovital GH3 being a proven whatever please provide references?

[mike250]

addison's and cushing syndrome are the extremities. adrenal fatigue tends to be the majority of the people under the inverted U-curve. I think it depends which levels of adrenal sufficiency you've reached.

[zoolander]

you mean adrenal insufficiency

[biknut]

I got a lot of information posted here.

http://www.imminst.o.....vital h3&st=0

Life Extension Foundation

LIFE EXTENSION DRUG NUMBER 6

LIFE EXTENSION DRUG GH3 or K.H.3
GH3 and K.H.3 are popular products whose active agent is procaine, an anti-aging compound discovered in the 1950s by Romanian physician Ana Asian. Both GH3 and K.H.3 suppress monoamine oxidase (MAO) levels. Elevated MAO destroys the essential neurotransmitters dopamine and norepinephrine. GH3 or KH3 also suppress elevated serum cortisol levels, which has been linked to several of the degenerative diseases of aging. There are better cortisol suppressing therapies such as low dose RU486, but at this time, RU-486 is not available to Americans.


Inhibition of adrenal cortical steroid formation by procaine is mediated by reduction of the cAMP-induced 3-hydroxy-3-methylglutaryl-coenzyme A reductase messenger ribonucleic acid levels.
Xu J, Lecanu L, Han Z, Yao Z, Greeson J, Papadopoulos V.

Division of Hormone Research, Department of Cell Biology, Georgetown University Medical Center, 3900 Reservoir Road, Washington, DC 20057, USA.

Elevated glucocorticoid levels are associated with many diseases, including age-related depression, hypertension, Alzheimer's disease, and acquired immunodeficiency syndrome. Cortisol-lowering agents could provide useful complementary therapy for these disorders. We examined the effect of procaine and procaine in a pharmaceutical formulation on adrenal cortical steroid formation. Procaine inhibited dibutyryl cyclic AMP (dbcAMP)-induced corticosteroid synthesis by murine Y1 and human H295R adrenal cells in a dose-dependent manner without affecting basal steroid formation. Treatment of rats with the procaine-based formulation reduced circulating corticosterone levels. This steroidogenesis-inhibiting activity of procaine was not observed in Leydig cells, suggesting that the effect was specific to adrenocortical cells. In search of the mechanism underlying this inhibitory effect on cAMP-induced corticosteroidogenesis, procaine was found to affect neither the cAMP-dependent protein kinase activity nor key proteins involved in cholesterol transport into mitochondria, cytochrome P450 side chain cleavage enzyme _expression, and enzymatic activities associated with cholesterol metabolism to final steroid products. However, procaine reduced in a dose-dependent manner the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity and the dbcAMP-induced HMG-CoA reductase mRNA levels by affecting mRNA stability. These data suggest that the inhibitory effect of procaine on cAMP-induced corticosteroid formation is due to the reduced synthesis of cholesterol. This modulatory effect of procaine on HMG-CoA reductase mRNA _expression was also seen in dbcAMP-stimulated Hepa1-6 mouse liver hepatoma cells. Taken together, these results suggest that procaine may provide a pharmacological means for the control of hormone-induced HMG-CoA reductase mRNA _expression and hypercortisolemia.

PMID: 14560037 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm....t_uids=14560037

[krillin]

One thing I can say about GH3 is it's hard to take properly. It must be taken on a empty stomach and you can't eat anything for 45 minutes after. Also, another big problem with GH3 is a lot of brands are total fakes with no procaine hydrochloride at all in them.

The brand I buy is Romanian, Gerovital H3, made by S.A. Sicomed.

I take (until the bottle runs out) one Tierra (from Beyond a Century) tablet an hour before breakfast, based on your success with this brand reported last year.

[krillin]

7-keto DHEA is the only anti-cortisol treatment that worked (past tense, unfortunately) for me, as rated by ability to relieve neck and shoulder tension from mold allergy. 

Did you try higher doses of Vitamin C?

I've been taking 2 x 1 gram since years before the mold sensitization. Would anything higher make a difference?

[krillin]

what about stress reduction techniques? I'm betting a regular routine of mindful mediation and awareness training would trump any cortisol reducing medication/supplement for reducing cortisol overtime.

I'm a big fan of the Sirius light and sound machine. I can actually get my arms and legs to feel heavy with it, and it helped me get to sleep when I was in the mold belt.

Can those who are stating that Gerovital GH3 being a proven whatever please provide references?

Here are some contrary references. This is definitely a YMMV supplement.

Biol Psychiatry. 1987 Sep;22(9):1107-26.
Intravenous procaine as a probe of limbic system activity in psychiatric patients and normal controls.
Kellner CH, Post RM, Putnam F, Cowdry R, Gardner D, Kling MA, Minichiello MD, Trettau JR, Coppola R.
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda 20892.

Evidence from animal and human studies suggests that procaine hydrochloride may selectively activate limbic system structures and suppress neocortical structures. We administered a series of intravenous bolus doses of procaine hydrochloride to 31 subjects (7 with affective disorders, 17 with borderline personality disorder, and 7 healthy normal volunteers). Dose-related cognitive and sensory distortions and illusions were observed; affective experiences ranged widely from euphoric to dysphoric. Topographic electroencephalogram (EEG) analysis indicated selective increases in fast activity (26-45 Hz) over the temporal lobes; the degree of increase in this activity correlated with degree of dysphoria experienced. Procaine was associated with increases in secretion of cortisol, adrenocorticotrophic hormone (ACTH), and prolactin, but not with growth hormone. These preliminary data are consistent with the possibility that procaine might serve as a clinically useful probe of psychosensory, affective, electrophysiological, and endocrine effects referable to the limbic system.

PMID: 2820518

J Pharmacol Exp Ther. 1994 Mar;268(3):1548-64.
Effects of local anesthetics on experiential, physiologic and endocrine measures in healthy humans and on rat hypothalamic corticotropin-releasing hormone release in vitro: clinical and psychobiologic implications.
Kling MA, Gardner DL, Calogero AE, Coppola R, Trettau J, Kellner CH, Lefter L, Hart MJ, Cowdry RW, Post RM, et al.

Clinical Neuroendocrinology Branch, National Institute of Mental Health, Bethesda, Maryland.

Local anesthetics, given i.v. to treat cardiac arrhythmias and for regional anesthesia, exert prominent central nervous system side effects, such as sensory distortions and mood changes. In experimental animals, these drugs activate limbic structures, such as the amygdala, that may coordinately regulate sensory processing, mood and pituitary hormone secretion during stress. Clinically relevant i.v. doses of the short-acting local anesthetic procaine were administered to 17 healthy volunteers and topographic electroencephalographic (EEG) spectra, stress-responsive neuroendocrine and cardiovascular parameters and sensory-cognitive and mood changes were examined. Because corticotropin-releasing hormone (CRH) mimics the behavioral and physiologic responses to stress and activates limbic structures in experimental animals, the effects of procaine and lidocaine on immunoreactive CRH release from rat hypothalami in vitro were also explored. Procaine administration produced a dose-related increase in fast (21-50 Hz) EEG activity, a significant decrease in alpha EEG activity and dose-dependent increases in heart rate, systolic blood pressure and plasma adrenocorticotropic hormone, cortisol and prolactin secretion. Dose-dependent increases in sensory distortions involved virtually all modalities, particularly auditory, visual and somatosensory. Mood changes occurred in most subjects, including anxiety, euphoria and arousal. In vitro, procaine and lidocaine both produced significant dose-related increases in immunoreactive CRH release from rat hypothalami, maximal at 10(-6) M, that were blocked by carbamazepine, a limbic anticonvulsant used in the management of mood disorders. The electrophysiologic effects of procaine in these volunteers were analogous to local anesthetic effects in experimental animals and consistent with the activation of subcortical structures localized within the temporal lobe, such as the amygdala. The effects of procaine on stress-responsive neurohormones were similar to those of amygdala stimulation both in experimental animals and human subjects. The in vitro data suggested that procaine-induced pituitary-adrenal activation involves stimulation of hypothalamic CRH, although additional (e.g., limbic-hypothalamic) mechanisms may contribute in vivo. These data were compatible with a direct action of local anesthetics on limbic structures that might account for many of the central effects seen with the systemic use of these agents in clinical practice.

PMID: 8138967

[Shepard]

Did you try higher doses of Vitamin C?

I've been taking 2 x 1 gram since years before the mold sensitization. Would anything higher make a difference?

Most studies have shown somewhere between 2 and 4 grams to be effective, IIRC.

[mike250]

you mean adrenal insufficiency

yep or moreso secondary adrenal insufficiency, if its quite severe then I think medical interference might be necessary. I'm surprised that some doctors don't know about it.

[biknut]

I take (until the bottle runs out) one Tierra (from Beyond a Century) tablet an hour before breakfast, based on your success with this brand reported last year.

That's a good brand that I like, but the S.A. Sicomed brand is just as good or better. I guess the main reason I favor it is because it usually cost less. I bought a big pile of it on ebay for about $5 a bottle.

[krillin]

Did you try higher doses of Vitamin C?

I've been taking 2 x 1 gram since years before the mold sensitization. Would anything higher make a difference?

Most studies have shown somewhere between 2 and 4 grams to be effective, IIRC.

I ramped up to 3 x 3 grams before giving up on it and returning to 2 x 1 gram. Didn't even give me the squirts.

Next in the queue is nicergoline, to enhance the glutamate reuptake that cortisol impairs. And if that fails, Keppra's up next. (I had to fail on 2.4 grams Neurontin before the doc would prescribe it. It doesn't even give me side effects. At least Lyrica had the decency to work for 6 weeks.)

Does this mechanism sound right? Allergen triggers cytokine release (without histamine degranulation, thanks to mast cell stabilizers like citrus bioflavonoids) -> cortisol -> impaired glutamate transport -> tonic muscles (calves, shoulders, jaw) clench up, anxiety

I'm out of the mold cloud now, so anxiety and calf and jaw problems are gone. All that's left are head, neck, and shoulder tension, facial tingling in the trigeminal area, and 10 pounds of water retention. Joint inflammation is also down (don't need my wrist brace to type anymore), but my CRP just came back at 1.57 mg/l. I had hoped that quercetin (1 gram!) would inhibit cytokine release, but that was a bust.

[lucid]

Not that I would recommend this but, Ketoconazole, the agent in dandruff shampoo nizoral (the 2% is the best dandruff shampoo on the market), if taken as a pill can suppress glucocorticoid(corisol) synthesis, where it is used in the treatment of Cushing's disease. The only noted side effect is decreased testosterone. I wonder if a small dosage could be useful for life extension where as cortisol can be very dangerous. (It has also been studied as an anti-depressant which had good results though the Trial wasn't placebo controlled.)

Cortisol could be a pretty critical part in aging and can explain why the people who make it to 100 almost always say that religion was a crucial part of their lives. (The logic here being that believing in an afterlife and the act of praying (similiar to meditation) are stress reducing tendancies). Stress is a killer.

[niner]

krillin, it sounds like you have a whopping mold allergy. Obviously you'll want to reduce exposure as much as possible, and I expect you've already done that. Have you considered immunotherapy? I'm allergic to a handful of common environmental allergens, including mold, and get shots once a week. I cannot begin to tell you how much better I felt after I got up to my working dose on the immunotherapy. It was like night and day, and nothing else I tried worked.

[krillin]

Not that I would recommend this but, Ketoconazole, the agent in dandruff shampoo nizoral (the 2% is the best dandruff shampoo on the market), if taken as a pill can suppress glucocorticoid(corisol) synthesis, where it is used in the treatment of Cushing's disease. The only noted side effect is decreased testosterone. I wonder if a small dosage could be useful for life extension where as cortisol can be very dangerous. (It has also been studied as an anti-depressant which had good results though the Trial wasn't placebo controlled.)

Cortisol could be a pretty critical part in aging and can explain why the people who make it to 100 almost always say that religion was a crucial part of their lives. (The logic here being that believing in an afterlife and the act of praying (similiar to meditation) are stress reducing tendancies). Stress is a killer.

Ketoconazole also can damage the liver. If one were to go the cortisol synthesis inhibition route, I think metyrapone would be best. Blocking 11B hydroxylase just lowers cortisol, corticosterone, and aldosterone. But ACTH rises as a result, and who knows what the increased ACTH stimulus will do to the adrenals?

http://www.indstate....d-hormones.html

[Matt]

I ramped up to 3 x 3 grams before giving up on it and returning to 2 x 1 gram. Didn't even give me the squirts.

I think its important you use all methods possible. Taking 2g of vitamin C is fine and its probably worth it in the long run. Studies have shown it blunts adrenaline and cortisol increase and prevents some of the symptoms associated with high levels of these. Personally it helped me loads! but took at least 1-2 weeks to start having an effect. Not only that, combining it with exercise or going for daily walk, fish oil, magnesium helps a lot too!

[krillin]

krillin, it sounds like you have a whopping mold allergy.  Obviously you'll want to reduce exposure as much as possible, and I expect you've already done that.  Have you considered immunotherapy?  I'm allergic to a handful of common environmental allergens, including mold, and get shots once a week.  I cannot begin to tell you how much better I felt after I got up to my working dose on the immunotherapy.  It was like night and day, and nothing else I tried worked.

You should've seen the mold and mildew injection sites from my allergy test. A coworker said they might have to cut my arm off. The shots haven't done anything at all after a year and a half, even though I've reached the maintenance dose. The only way I know they're not sugar water is that sometimes I get red circles from them. But no itching or swelling: phytochemicals seem to be very good at keeping histamine at bay.

One weird thing I've noticed is how quickly the tension goes away when I go outside. There must be a very rapid dynamic equilibrium going on. I also can't believe how badly I react to the indoor air here. There can't be THAT much mold indoors in Colorado. My only explanation is that chitin from all the dead bugs is mistaken for mold by my immune system.

Nature. 2007 May 3;447(7140):92-6.
Chitin induces accumulation in tissue of innate immune cells associated with allergy.Reese TA, Liang HE, Tager AM, Luster AD, Van Rooijen N, Voehringer D, Locksley RM.
Howard Hughes Medical Institute, Departments of Medicine and Microbiology/Immunology, University of California San Francisco, San Francisco, California 94143-0795, USA.

Allergic and parasitic worm immunity is characterized by infiltration of tissues with interleukin (IL)-4- and IL-13-expressing cells, including T-helper-2 cells, eosinophils and basophils. Tissue macrophages assume a distinct phenotype, designated alternatively activated macrophages. Relatively little is known about the factors that trigger these host responses. Chitin, a widespread environmental biopolymer of N-acetyl-beta-D-glucosamine, provides structural rigidity to fungi, crustaceans, helminths and insects. Here, we show that chitin induces the accumulation in tissue of IL-4-expressing innate immune cells, including eosinophils and basophils, when given to mice. Tissue infiltration was unaffected by the absence of Toll-like-receptor-mediated lipopolysaccharide recognition but did not occur if the injected chitin was pre-treated with the IL-4- and IL-13-inducible mammalian chitinase, AMCase, or if the chitin was injected into mice that overexpressed AMCase. Chitin mediated alternative macrophage activation in vivo and the production of leukotriene B(4), which was required for optimal immune cell recruitment. Chitin is a recognition element for tissue infiltration by innate cells implicated in allergic and helminth immunity and this process can be negatively regulated by a vertebrate chitinase.

PMID: 17450126