Phytoestrogens as therapeutics - anyone explored?

[Alchemica]

So who's explored phytoestrogens? I'm looking at ones that would act more as SERMs and be beneficial in mental illness. SERMs are quite neuroprotective, modulate things like DA beneficially and are promising for mental illness and neurodegenerative issues. Great cognitive improvers in illness. Mainly looking at ones that will act through ERβ. A gentle healing feminine energy for the body, mind, spirit and soul but not a feminising force for a male to be compromised with.

 

Something that could add depth to inner feminine dimensions safely. Some of the milder soy isoflavones may fit the bill but to be honest, I've never explored such. If anyone has expertise or experience, love to hear.

Actually I have a bit of daidzein which might be worth exploring

Warning: Removing dietary phyto-oestrogens in adult male rats causes obesity and diabetes in some models [1] and long-term consumption of a diet rich in soy isoflavones can have marked influences on patterns of aggressive and social behaviour [2].
 

 

Edited April 25, 2019 by Alchemica

[Alchemica]

So with today's cacao in the system, I'm going to explore some high AAU (14%) Galaxy Hops Pellets and see if I can add some phytoestrogen (highly potent phytoestrogen 8-prenylnaringenin) and anxiolytic (xanthohumol) dimensions. Not sure of the beta-acids levels in these but Hops increases GABA levels in rat brain homogenate by inhibiting GABA transaminase . Zanoli et al. have investigated the in vivo and in vitro effect of hop beta-acids on central nervous system function and suggested an antidepressant-like activity. Behavioral effects of beta-acids fraction were explained by a modification in the GABAergic activity.

 

I used to like the intoxication of beer but it was dirtied by alcohol messiness. Lets see what 2g of the pellets is like!

[Alchemica]

Yeah this was a nice blend. Ended up dosing in the evening with a bit of tryptophan chocolate which takes it to an even nicer place.

You could get beer chocolate. It's a good reflection of the Hops spirit, the Cacao and Hops mix. Add some other GABAergics like myristic acid as a fat source. Maybe other GABAergic phytochemicals, flavonoid or things like pinene which are BZD site GABAA modulators. Even magnolol/honokiol and a bit of ashwagandha extract

 

Cloudy, feminine, soft, anxiolytic, mellow hops spoke to me in this combo. Taste with the bitters of alpha-acids would be an acquired one, not sure if I can find a high beta-acid variety and what that tastes like.

[Alchemica]

So has anyone used soy lecithin as a choline source, health tonic, pro/remyelination strategy? Not very desired these days, why's that? Don't want to fork out for expensive things from china like CDP-choline. The PUFAs are a nice addition, I might isoflavone my lecithin up on the cheap. Just sprinkle it on food as required...
 

I'd actually welcome soy isoflavones if they crept in. Particularly genistein, a neuroprotective estrogen receptor (ER) β dependent modulator acting healthily on estrogenic/serotonergic systems for beneficial actions in the CNS - which I can get reasonably cheaply: chronic genistein administration to mice engenders antidepressant-like efficacy evidenced by lessened behavioral despair. Serotonergic system that preferentially couples with 5-HT1A receptors may be critically responsible for the present genistein anti-depression. Genistein <10mg/kg enhanced serotonergic transmission in the amygdala, including upregulation of tryptophan hydroxylase, serotonin, and phosphorylated (p)-CaMKII and p-CREB, as well. Genistein exerts anti-anxiety effects on a PTSD model probably through enhancing serotonergic system and CaMKII/CREB signaling pathway in the amygdala. It also acts on 5-HT3Rs.
 

Seizure-induced abnormalities improved partially only by the lower dose of genistein (0.5mg/kg).

Genistein may have restorative and preventive effects against cognitive impairment.

[Alchemica]

Up to cacao + 1.8mg/kg genistein, mixed in coconut MCTs and administered orally.

 

Contrary to beer which contains a potent phytoestrogen which attaches preferentially to ERα and is physically feminising, genistein is different. Beer drinkers are upping the physical/sexual feminisation, I'm upping the beneficial ERβ activity.
 

Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects
 

Coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits, contributing to cognition, with potential relevance for the development of novel estrogenic-based therapies for neurodevelopmental or neurodegenerative disorders.

 

Particularly useful for the mind are HERβAL ERβ agonists!
 

So what's a genistein dose like? You can get soy isoflavone caps which have like 50 or 60 mg of isoflavones with sometimes only 2-20mg genistein in them. I'm going deep to suss this one out... 15 or 45 mg/kg, p.o. exerted dose-dependently antidepressant-like effect in mice while 2-8mg/kg was injected intraperitoneally for anxiety in traumatised PTSD rats and 10mg/kg to prevent seizures. Many anti-carcinogenic effects of genistein are seen in the range of 10-20mg/kg I'll eventually work up to 3.7mg/kg going on the oral doses converted roughly to human equivalents, seeing how I go.

 

If you take it orally, it's suggested in the literature to take it with a prebiotic to prevent its degradation by gut bacteria - this one doesn't seem to form equol-type desired breakdown products so you want to divert away from genistein degradation.
 

ERβ is a key requirement for activation of mechanisms that underlie estrogen-inducible neuronal morphological plasticity, brain development, and cognition. ERα, on the other hand, is more predominant in mediating the sexual characteristics of estrogen effects in the reproductive organs such as breast anduterus. ERβ is a pharmacological target to promote memory function and neuronal defense mechanisms against age-related neurodegeneration such as Alzheimer’s disease (AD) and psychiatric disorders, while avoiding activating untoward estrogenic proliferative effects in the breast and uterus, although this might be at the cost of lower efficacy due to the lack of activation of ERα in the brain. Other potential therapeutic advantages associated with ERβ include regulation of estrogen vasculoprotective action and development of interventions targeting diseases such as depression, colon cancer, prostate cancer, obesity, leukemia, and infertility.
 

However, a potential disadvantage of an ERβ-selective ligand is the lack of activation of ERα in bone, as ERα has been demonstrated to mediate estrogen regulation of bone density.

Genistein has high selectivity for ERβ with strong serotonergic effects.

Males

A 2010 meta-analysis of fifteen placebo-controlled studies said that "neither soy foods nor isoflavone supplements alter measures of bioavailable testosterone concentrations in men." Furthermore, isoflavone supplementation has no effect on sperm concentration, count or motility, and it leads to no observable changes in testicular or ejaculate volume. A 2010 review suggested that the sperm count decline and the increasing rate of testicular cancers in the West could be linked to a higher presence of isoflavone phytoestrogens in the diet, even if this is not proved and must still be debated.

Females

It is unclear if phytoestrogens have any effect on the cause or prevention of cancer in females. Some epidemiological studies have suggested a protective effect against breast cancer. But a recent in vitro study concluded that females with current or past breast cancer may risk of tumor growth by consuming soy products, since they can stimulate the growth of estrogen receptor-positive cells in vitro. Low levels of genistein and daidzein, the phytoestrogens in soybeans, showed the potential to stimulate tumors, while protective effects were found at larger concentrations of the same phytoestrogen. A 2006 review article concluded that not enough information is available on the effects of phytoestrogens to justify drawing conclusions. While preliminary in vitro results suggest that isoflavins inhibit tumor growth, more research is needed to evaluate how isoflavones affect breast tissue in females at high risk for breast cancer. A more recent epidemiologic study argued that consumption of soy estrogens is safe for patients with breast cancer and that it may in fact decrease mortality and recurrence rates. Thus, even review studies have failed to produce consensus on the relationship between phytoestrogens and breast cancer.

 

It also remains unclear if phytoestrogens can minimize some of the deleterious effects of low estrogen levels (hypoestrogenism) resulting from oophorectomy, menopause, or other causes. A Cochrane Review of the use of phytoestrogens to relieve the vasomotor symptoms of menopause (hot flashes) concluded that there was no conclusive evidence to suggest any benefit to their use, although genistein effects should be further investigated. Another study reported that phytoestrogens such as genistein may help prevent photoaging in human skin and promote formation of hyaluronic acid.

Modulate DA

I've always wanted a way to drop mesolimbic DA activity while boosting mesocortical DA. Hypothetically part of a perfect strategy for me.

It wasn't long ago, being a bit of a big pharma-posessed person, I thought to go a SGA+dexamphetamine. Now I'm resonating with ERβ-selective phytoestrogens as a potentially great tool to healthily modulate DA nicely while at the same time boosting hippocampal-dependent functions, neurogenesis, neuroplasticity and providing neuroprotection - genistein adding serotonergic + other beneficial activity to boot.
 

ER agonists can powerfully modulate the responsiveness of the mesocortical dopaminergic system, increase the expression of key genes related to dopaminergic neurotransmission and augment the dopamine content of the PFC. Large increases in both dopamine and 3,4-dihydroxyphenylacetic acid content of the PFC are seen with modification of this system.
 

ERβ agonists prevent amphetamine induced PPI disruptions, likely by preventing mesolimbic DA hyperactivity.
 

There are sexually dimorphic aspects but it seems ERβ benefits are more conserved between the sexes? See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793919/
 

Maybe I can instill better long-term goal directed behaviour through ERβ modulation?

Disorders of the dopamine system, such as schizophrenia or stimulant addiction, are associated with impairments in different forms of cost/benefit decision making. The neural circuitry (ie amygdala, prefrontal cortex, nucleus accumbens) underlying these functions receives dopamine input, which is thought to have a central role in mediating cost/benefit decisions. Estradiol modulates dopamine activity, and estrogen receptors (ERs) are found within this neurocircuitry, suggesting that decision making may be influenced by estradiol.
 

Agonists modulate cost/benefit decision making, whereby concomitant activation of ERα and β receptors shifts the decision criteria and reduces preference for larger, yet more costly rewards.

Oxytocin and Vasopressin - Social dimensions
 

I never responded with benefit on the whole in any way to potent therapeutic and supra-therapeutic doses of oxytocin via multiple RoAs. Always felt it was a missing dimension for me endogenously. Why was this 'miracle cure' so crappy for me?
 

Oxytocin (OT), has gained widespread attention as a potential therapeutic agent in a myriad of disorders, including autism spectrum disorder, schizophrenia, and addiction.
 

Yet results are so variable. What if I simply need to induce some of the good stuff a different way? Maybe ERβ agonist phytoestrogens that also have strong effects on serotonergic systems, including 5-HT1ARs, are potently useful as a pro-social tool? I aim to test that a bit!
 

Maybe I can get these pro-social systems cranking another way: Steroid hormones differentially modulate stress responses and alter OTR expression. In particular, estrogen receptor β activation has been found to both reduce anxiety-related behaviors and increase OT peptide transcription, suggesting a role for OT in this estrogen receptor β-mediated anxiolytic effect. ERβ activation plays a critical role in estrogenic regulation of OT and AVP gene expression in the PVN.

Weight loss

Having a bit of belly fat I want to slaughter, I might get around to applying this cream... these ERβ ligands reduce obesity and metabolic diseases in mice by converting bad fat (white fat) to good fat (brown fat). This is significant as brown fat increases metabolism and may facilitate weight loss. Don't need new agonists when nature provides them!
 

Animals fed a high-fat diet showed a significant increase in body weight, and this weight gain was attenuated by ERβ ligands. High-fat diet-mediated increases in serum cholesterol, leptin, glucose, and fat accumulation in organs were also reduced by ERβ ligands. In addition, MRI scanning indicated that ERβ ligands altered body composition by reducing fat mass and increasing lean body mass. Organ weights and gene expression analyses demonstrated that adipose tissue is the center of action for ERβ ligands, and the reduction in body weight is likely due to increased energy expenditure. In vitro and in vivo mechanistic studies indicated that the anti-obesity effects were due to indirect peroxisome proliferator-activated receptor γ
 

Impairment of insulin and glucose metabolism by ERβ may have significant implications for our understanding of hormone receptor-dependent pathophysiology of metabolic diseases, and may be essential for the development of new ERβ-selective agonists.

More info

 

In premenopausal women (20 to 43 y) administered 0.4 - 0.8 mg/kg:

 

Serum concentrations of [13C]genistein and [13C]daidzein peaked after 5.5 and 7.4 h, respectively. The systemic bioavailability and maximum serum concentration of [13C]genistein were significantly greater than those of [13C]daidzein. The bioavailability of both isoflavones did not increase linearly when the dietary intake was doubled. The mean volume of distribution normalized to bioavailability (Vd/F), clearance rate, and half-life of [13C]daidzein were 336.25 L, 30.09 L/h, and 7.75 h, respectively; the corresponding values for [13C]genistein were 258.76 L, 21.85 L/h, and 7.77 h. The average recovery of [13C]daidzein and [13C]genistein in urine was 30.1% and 9.0% of the dose ingested, respectively.

 

The value for AUCinf for [13C]genistein was significantly greater (P < 0.05) when the isoflavone dose was increased to 0.8 mg/kg body wt. Like [13C]daidzein, however, the mean values for the bioavailability of [13C]genistein did not double with a doubling of the intake of isotope [6.33 (moderate dose) compared with 9.77 (mean for the low dose and low dose repeat) μmol · h/L]. Cmax also significantly increased in 2 of the low-dose regimens compared with the moderate dose (P < 0.05). The values for Cmax and AUCinf were unaffected by prior exposure to isoflavones (low dose after food). For AUCinf, the mean was slightly lower, but the difference was not significantly different from the values for other low-dose regimens. The calculated t1/2, CL, and Vd/F were not significantly different among the dosing regimens.

http://ajcn.nutrition.org/content/77/2/411.full

Edited July 19, 2017 by Alchemica

[Alchemica]

While we're at it, just modulate everything for me!
 

What known systems does ERβ agonism modify? In addition to the other aspects I've mentioned:
 

ERβ-mediated processes relate to regulation of transcription, translation, neurogenesis, neuromodulation, and neuroprotection
 

The alterations in transmitter signaling include the serotonergic; GABAergic; glutamatergic; adrenergic/noradrenergic; and cholinergic systems. In the case of peptidergic signaling mechanisms, the local production of CCK, cholecystokinin and PDYN, prodynorphin is influenced. Various peptide hormone receptors are also regulated. This group reflects changes in GAL, galanin; GnRH, gonadotropin-releasing hormone; POMC, pro-opiomelanocortin; PRL, prolactin; CRH, corticotropin-releasing hormone; ANG, angiotensin; PACAP, pituitary adenylate cyclase-activating polypeptide; and BK, bradykinin neurotransmission/modulation. Growth hormone and trophic factor production is also highly targeted. A strong regulatory effect is exerted upon certain potassium channels. Synaptic vesicle proteins are also regulated. Transcription factors show altered expression accompanied with modification of RNA processing, translation and protein synthesis. These complex mechanisms may regulate neurogenesis and synaptic plasticity
 

This includes genes encoding growth factors (Igf2, Igfb2, Igf1r, Fgf1, Mdk, Ntf3, Bdnf), transcription factors (Otx2, Msx1), potassium channels (Kcne2), neuropeptides (Cck, Pdyn), peptide receptors (Crhr2, Oprm1, Gnrhr, Galr2, Sstr1, Sstr3), neurotransmitter receptors (Htr1a, Htr2c, Htr2a, Gria2, Gria3, Grm5, Gabra1, Chrm5, Adrb1), and vesicular neurotransmitter transporters (Slc32a1, Slc17a7).
 

See: http://journal.frontiersin.org/…/10.3…/fncel.2016.00149/full

~~~

Another aspect I'm interested in seeing resolve is my sleep difficulties. It's a huge issue and I've tried everything. Now I just use a sedating antihistamine dose when I need but it would be nice to not need that. Sick of having poor quality sleep.
 

While androgens drive DA/NE arousal systems, I'm adding a bit of mellowness to that. It feels calming! Had a nap on the 1.8mg/kg...
 

It appears that the hormones estrogen, progesterone, and testosterone play a role in the regulation of circadian rhythm in animals.

Gonadal steroid receptors are expressed in almost every site that receives direct SCN input and cause differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamic-adrenal-pituitary (HPA) axis, and sleep-arousal systems. Disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease.
 

Hormone signalling during critical periods organises the adult circadian timekeeping system by altering adult hormone sensitivity and shaping fundamental properties of circadian rhythmicity.

[Alchemica]

First a recipe! Cacao based:
 

Cacao, coconut, rosehip, soy and lavender body butter attempt. Small scale.

10mL (2 tsp) coconut 90% MCTs [supermarket liquid coconut oil from the fancy cooking oils section]
10g raw cacao butter [Health food shops]
qs rosehip oil
Lavandula angustifolia essential oil [Thursday plantation lavender oil from the supermarket] or EO of choice
Pure genistein/cacao alkaloids - dose as required*

Over warm water, heat the coconut oil and add the genistein and/or cacao alkaloids. Stir to dissolve as well as possible, if you keep the dose low you should find it will mostly dissolve. I tried with 100mg and some of it remained in the oil at 5mL, better at 10mL. Add as many drops of lavender oil as your body needs, I did quite a few (500mg oil). Add the cacao butter to the warm oil while stirring. Add some drops of rosehip oil as desired (I used about 10).

Allow to cool.

The coconut oil MCTs are called, when used this way, penetration enhancers. They help the actives penetrate the skin.

The Lavender modulates the autonomic nervous system and possibly has other health benefits. Inhalation modulates the transcription of deleterious stress effects on various brain chemicals, normalising the effects of stress. At 80mg orally it as as effective as lorazepam and paroxetine for generalised anxiety!

The genistein is a soy isoflavone that selectively modulates a special estrogen receptor - good for the body, mind, spirit and soul. Be cautious and don't use if you have breast cancer although evidence is not in anyway conclusive, it may actually be helpful. Doses of genistein should maybe be around 20mg in a serve of cream for women, higher for medicinal applications?

Cacao alkaloids up to 200mg/serve

This gives a butter that has a skin/warm roomtemp-ish melt in your fingersness

What's my thoughts on transdermal genistein? Hard to tell. @100mg If it's infusing into my bloodstream it's doing it a really nice gentle subtle way - could be useful. Until I can get solid evidence that it's reaching my brain I'm going to do dual application oral and transdermal. Split my doses. Infuse that HERβAL CNS healing into me both ways. Hopefully the transdermal should mellow out the peaks and troughs of oral administration all going well. This is just short-termish while I see how much this helps my brain along!

~~~

So for anyone males wondering. Does genistein at mega doses acutely affect your primal manliness? Important for some, not so much me.

So far it doesn't seem to but I haven't fully experimentally verified that. Manly primal functions still there but it's less important to be even worried about sex or anything. Just interested in people and company and helping and love and all that.
 

It's a better state of manliness. You get your testosterone stuff as required, in the background awaiting loving use, plus a new social-emotional dimension which is way more fascinating and satisfying than a root...

I'll keep an eye on this dimension but yeah ERβ agonism is so far super man friendly. Just maybe don't try 1.8mg/kg too quickly.

In the name of science: Verified while I'm super HERβ'd on genistein, don't know if I'll be dosing to these doses again - No need for PDE5 inhibitors, more of a need to get in the state, adds some level of porn star duration dimensionality possibly through 5-HT? More emotional dimensions....

Using this in brain injury
 

Following brain injury, microglia and astrocytes assume a reactive-like state and secrete pro-inflammatory molecules that can potentiate damage. A therapeutic strategy that may limit this is of potential interest. In this context, selective estrogen receptor modulators, such as raloxifene and tamoxifen, are known to reduce microglia activation induced by neuroinflammatory stimuli. I'm doing it naturally.
 

There is strong observational evidence for estrogen enhancement of certain aspects of cognitive functioning

Estrogen has neuroprotective and neurotrophic actions that may be mediated by a variety of routes. Estrogen receptors (both alpha and beta forms) have been found in microglia and within reactive astrocytes. In addition, there is evidence that estrogen suppresses activation of microglia and astrocytes and thereby the inflammatory cascade. Circulating estrogen is critical to the health of some types of neurons. This has been clearly demonstrated for a subpopulation of dopaminergic neurons in the substantia nigra. It is not yet clear whether this effect on dopaminergic neurons is mediated via the intracellular estrogen receptor or by a plasma membrane receptor for estradiol, although the antioxidant actions of estrogen have been implicated.
 

The neuroprotective actions of estrogen have been convincingly demonstrated in animal models of ischemia, contusion, hypoxia, and drug-induced toxicity

Epigenetic effects!

(ERβ) is a ligand-inducible transcription factor regulating gene expression in response to the female sex hormone oestrogen. Previously, we found that ERβ deficiency results in changes in DNA methylation patterns at two gene promoters, implicating an involvement of ERβ in DNA methylation.

[Alchemica]

Back on track for an attempt with clean socialising just with a solid dose of genistein (2mg/kg) today.

Aim for catching up with a good friend if I can, otherwise I'll do something social. Challenge is to stay away from needing anything vicey detrimental in the way of anxiolysis.
 

That's pushing the dose but still not quite at the upper 3.7mg/kg human equivalent that was used as an antidepressant in one study. Content with the energy and working with it, no longer feels alien. It's soft energy but I like a bit of softness.

Been sticking with this long enough, just a couple of days, that I might be starting to get the neurogenic, systems level epigenetic, frontal cortical DA upregulation, pro-social 5-HT1A, oxytocin and vasopression transcription, upregulation of tryptophan hydroxylase, serotonin, and phosphorylated (p)-CaMKII and p-CREB and neuroplastic shifts coming in slowly.

 

While something was acutely notable, like a plasticity and cognitive shift for the better, the serotonergic effects were verified in mice at day 7. Considering I'm trying to medicate some heavy pathology beyond depression (though that comes with the terrain), not expecting rapid shifts on a heavily scarred brain.

 

ERβ, antidepressant responses, BDNF and 5-HT2A!
 

"...sex-unspecific regulation of ERβ by the stress and by antidepressants and its differential convergence with bioenergetics and apoptotic pathways in females and males implies its role as a vulnerability factor in the stress response and emphasizes mitochondrial ERβ-dependent pathways as an important gateway of ADs action, at least in females."
 

https://www.ncbi.nlm.nih.gov/pubmed/28716632
 

"ERβ agonism significantly enhanced BDNF/TrkB signaling and the downtream cascades involved in synaptic plasticity. Subsequent study in ERβ mutant rat models demonstrated that disruption of ERβ was associated with a significantly elevated level of 5-HT2A but not 5-HT1A in rat hippocampus, indicating ERβ negatively regulates 5-HT2A. Additional analyses in primary neuronal cultures revealed a significant association between BDNF and 5-HT2A pathways, and the data showed that TrkB activation downregulated 5-HT2A whereas activation of 5-HT2A had no effect on BDNF, suggesting that BDNF/TrkB is an upstream regulator of the 5-HT2A pathway. Collectively, these findings implicate that the disruption in estrogen homeostasis leads to dysregulation of BDNF-5-HT2A signaling and weakened synaptic plasticity, which together predispose the brain to a vulnerable state for depression. Timely intervention with an ERβ-targeted modulator could potentially attenuate this susceptibility and reduce the risk or ameliorate the clinical manifestation of this brain disorder."

https://www.ncbi.nlm.nih.gov/pubmed/28544903

 

Use of phytoestrogens/SERMs in psychotic spectrum illnesses
 

Well as desired, the behavioural preservation is slowly lifting, by either intent or phytochemical intervention, likely a combination. More open to the world around me.

 

My stress-induced coprolalia/obsessive compulsive symptoms (OCS) are there but diminished? These symptoms are considered highly treatment refractory and worsened by traditional pharmacotherapies. The current consensus is that it is a disruption of particularly serotonergic signalling, particularly 5-HT2A and pharmacological antagonism adds to it. However many phamacological therapies depend on D2/5-HT2A antagonist action to exert efficacy. That said, it appears targeting 5-HT2A through downregulation indirectly via estrogenic signalling could be a new, unexplored, therapeutic avenue. With such signalling, you also get the correct dopaminergic corrections, without antagonising anything!
 

This is highly prevalent and an unmet treatment need for a significant population of people with psychotic-spectrum illnesses. My psychosis may be organic and really well controlled (no positive symptoms!) but the OCS are debilitating: See https://www.ncbi.nlm.nih.gov/pubmed/28189922
 

"Although obsessive-compulsive symptoms (OCS) in schizophrenia have been conceptually controversial and clinically challenging, recent evidence suggests that schizophrenia with OCS may constitute a distinct schizophrenic subgroup. Recent epidemiological and clinical findings have shown that the subgroup obsessive-compulsive (OC) schizophrenia is associated with poor outcome and is more frequent than previously realized. Emerging biological evidence suggests that OCS in schizophrenia has more than one pathogenesis, with distinct mechanisms that may require different treatment interventions"

https://www.ncbi.nlm.nih.gov/pubmed/19944887

 

Genistein at high doses seems robustly healing as the current literature is discovering. In males and females. Why use synthetic SERMs when natural long-term safe options are provided by nature! This is a functional food option that can be titrated by the consumer!

 

It is intriguing to see that raloxifene as an adjunct to neuroleptics improves cognition and reduces symptom severity in men and women with schizophrenia even in treatmentresistant psychosis. A recent meta-analysis investigating symptom reduction reviewed numerous clinical trials and found that raloxifene adjunct therapy had a more profound effect on the negative symptoms and cognition than on positive symptoms. Because negative symptoms and cognitive impairments are more strongly linked with structural abnormalities in the brain than with positive symptoms, the findings that raloxifene improves cognition (information processing) and reduces negative symptoms in treatment-resistant psychosis may be a result of improved neuronal and synaptic density and connectivity that is disrupted in schizophrenia, particularly in the cortico-striatal region. Furthermore, because cognitive impairments are seen long before the onset of first signs of schizophrenia, (i.e., the positive and negative symptoms), early intervention with raloxifene in schizophrenia may produce more satisfactory results in terms of improving cognition, general psychopathology, and correcting the illness at an early stage.
 

The observations that raloxifene increases forebrain neurogenesis in the injured brain and enhances working memory and synaptic plasticity in the animal models of neurodegeneration suggest that it has potential brain- and behavior-reparative properties in addition to its potential anti-oxidant and anti-inflammatory effects. Oxidative stress and neuroinflammation exist and probably cause several neurodegenerative diseases including autism, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease; thus, raloxifene is worthy of intervention in these hard-wired brain diseases.

Edited July 24, 2017 by Alchemica

[Alchemica]

Genes, Gender, Environment, and Novel Functions of Estrogen Receptor Beta in the Susceptibility to Neurodevelopmental Disorders.

It is proposed that perturbed estrogenic signaling in the fetal brain due to aberrant DNA methylation of the estrogen receptor β (ERβ) gene, and such methylation patterns, may be imprinted to future generations and could theoretically increase subsequent neurodevelopmental disorders such as ASD offspring risk. Exposure to endocrine-disrupting components in the environment and even pharmaceuticals, including hormonal contraceptives may increase the risk.
 

ERβ-/- mice display a defective migration and layering of cortical neurons as well as impaired spatial learning and increased anxiety behavior. Such behaviors have not been shown for ERα-/- mice, suggesting that ERβ is the main ER isoform in regulating neuronal development associated with cognitive and affective behaviors. ERβ is crucial in the developing brain. However, its mechanistic understanding here is far from clear. In adult rodents, it has been shown that ERβ is expressed in serotonergic neurons of the dorsal raphe nucleus, where it mediates E2-dependent tryptophan hydroxylase (TPH) production, the rate-limiting enzyme for serotonin synthesis, and maintenance of serotonergic neurons. ERβ is also the main ER isoform in dopaminergic (DA) neurons of the substantia nigra. It is well established that E2 promotes neuroprotection of these DA neurons. However, it is not clear if it is a direct effect of E2 on these neurons or if E2 exert its neuroprotective effect through oligodendrocytes, microglia, or astroglia. Interestingly, both oligodendrocytes and microglia express mainly ERβ. ERβ could rapidly alter transmission in the mPFC to alter PFC-dependent behaviors. ERβ opposes AR signaling and inflammation
 

New studies have suggested that ERβ may play a more important role during neuronal development, as well as having new functions in regulating temporal DNA methylation dynamics. Treatment with ERβ agonist causes a significant decrease in DNA methylation globally.

This strategy potently promotes remyelination (this has important implications for neuroprotective therapies that directly target oligodendrocyte survival and myelination - ERβ ligand therapy activates PI3K/Akt/mTOR signaling in oligodendrocytes and promotes remyelination)
 

See: https://www.ncbi.nlm.nih.gov/pubmed/28362134 for effect on male germline

 

[Alchemica]

Sitting with a functional blend at the moment. Cacao powder, bit of cinnamon metabolite, N-acetylcysteine and genistein. Don't want to add more for once.

I'm finding the combination of phytoestrogen ERβ agonism (pushed the dose for a bit, this stuff is friendly, now it seems to be kind of a PRN thing if I require a prosocial shift) with 2400mg/day N-acetylcysteine is tackling impulsivity, obsessive compulsive dimensions and coprolalia really well. Doing this while keeping mood good and cognition sharp. Restoring feeling in control. Giving me control over my life to reprogram it in a healthy direction.

 

Most people don't understand this dimension at all. Always struggled with some dimensions of impulsivity but after my suicidal injuries, I started developing extreme addictions which just cascaded. Got to the point of more suicide attempts and more organic neuropsychiatric problems from such. From extreme obsessive compulsiveness, coprolalia, tics, impulsivity particularly on substance cues - it makes a vicious unescapable cycle happen if we don't appropriately target this therapeutically.
 

The ERβ agonism tapers down hyperactive mesolimbic dopamine while boosting mesocortical dopamine and allows a shift from seeking high reward, high risk things to a healthier state where executive function high order cognition starts to be restored. It also induces a prosocial shift,  transcriptional oxytocin modulation etc, restores a loving energy. It also targets serotonergic aspects of obsessive compulsive and impulsive behaviours.

 

The N-acetylcysteine tapers down glutamate through the cystine/glutamate exchange system in things like the often damaged OFC. This helps prevents obsessive compulsive dimensions, improves the coprolalia too. It also reverses drug-induced metaplasticity and provides relapse protection.

 

Vulnerability to relapse is a cardinal feature of addictions, and the glutamatergic projection from the prefrontal cortex (PFC) to the nucleus accumbens core (NAc) has been identified as a potentially important neural mediator of relapse. In addiction, there is insufficient for normal mGluR2/3 activation, thereby increasing PFC-NAc glutamate release probability. N-acetylcysteine helps target this.

 

Through mGluR2/3s social deficits in autism spectrum disorders are also targeted.

A page on phytoestrogens as therapeutics: https://www.facebook.com/Phytoestrogens-as-therapeutics-126178541328922/