Author Topic: Prevention and relief with plant sterols and sterolins (Moducare)  (Read 25176 times)

Quantum

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Re: Prevention and relief with plant sterols and sterolins (Moducare)
« Reply #40 on: January 20, 2015, 11:12:57 PM »
I only took a 500mg pill right before bed that day but before then i had not taken any for months. I will try it the way you described, i figured 500mg is to much anyways.
I see you mention rosemary, a poiser mentioned it helped them recover faster.

Rosemary is one of my best POIS-relieving supplement.  The rosmarinic acid in it is an excellent IDO inhibitor ( http://en.wikipedia.org/wiki/Rosmarinic_acid#Clinical_importance) , so it is good for blocking the transformation of tryptophan in kynurenine.  It is one of the best also as prevention, when I take it in my pre-O pack, one hour before O.  Rosemary is also a very good antioxidants source.  I have noticed years ago that rosemary was good for me, way before knowing about the role of IDO and tryptophan in my POIS. 

if you go to the link I gave above, you will also read that rosmarinic acid has anxiolytic properties, via the inhibition of the GABA transaminase enzyme.  No surprise it helps me a lot against POIS, my main symptoms being emotional symptoms, including anxiety.

My favorite and most effective way to take rosemary, and also very low cost, is to use rosemary essential oil.  I put 1 drop in a glass of water, mix it, and drink as needed (never put more than 1 or 2 drops in a glass of water, essential oils are highly  concentrated).  If you can bare the camphor-like taste of the rosemary essential oil,which is not that bad, that's much more efficient and faster than eating rosemary.  My "rosemary water" is good for all POIS symptoms, and the one most effective way to correct my POIS-induced hypotension (if I didn't take my pre-O pack and get symptoms ). Furthermore, 25mg of 5-HTP taken with rosemary water is very, very effective for me.

Other spices/herbs also contains rosmarinic acid, and are good for POISers as well: curcumin, oregano, sage, marjoram, peppermint oil, lemon balm, basil.  They are all anti-inflammatory and anxiolytic, some more than others ( rosemary and curcumin are my favorites).  I started to put more spices in what I eat, last year, after reading about the benefits of peppered curcumin and other spices as well.  I didn't know that would help me eventually with POIS :)

You are totally right, go slowly with your tryptophan dose.  It is better to take less, like 200mg. and take more a few hours later, than take too much and being stuck with side effects.
« Last Edit: January 20, 2015, 11:19:55 PM by Quantum »
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G-man

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Re: Prevention and relief with plant sterols and sterolins (Moducare)
« Reply #41 on: February 05, 2015, 11:35:43 PM »
The concept of depression as a dysfunction of the immune system

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002174/?report=classic

"Chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis and the immune system, acts as a trigger for anxiety and depression. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids, as occurs in chronically stressful situations and in depression, contribute to the behavioural changes associated with depression.

A defect in serotonergic function is associated with hypercortisolaemia and the increase in proinflammatory cytokines that accompany depression. Glucocorticoids and proinflammatory cytokines enhance the conversion of tryptophan to kynurenine. In addition to the resulting decrease in the synthesis of brain serotonin, this leads to the formation of neurotoxins such as the glutamate agonist quinolinic acid and contributes to the increase in apoptosis of astrocytes, oligodendroglia and neurons.

The importance of the inflammation hypothesis of depression lies in raising the possibility that psychotropic drugs that have a central anti-inflammatory action might provide a new generation of antidepressants."

...

"Until recently, the brain was considered to be an immunologically privileged organ that was protected from the peripheral immune system by the blood-brain-barrier. It is now apparent that this view is incorrect and that the brain is directly influenced by peripherally derived cytokines, chemokines, prostenoids and glucocorticoids, as well as some immune cells, that can access the brain and thereby influence those neuronal networks that appear to be malfunctioning in depression [9]. The influence of large molecules from the periphery on the brain is somewhat surprising as specific transporters for peptides such as the interleukins do not appear to be present at the blood-brain-barrier. Nevertheless, there is now experimental evidence to indicate that such molecules could access the brain a) via a leaky blood-brain-barrier that occurs in major depression, b)by activation of endothelial cells that line the cerebral vasculature and produce inflammatory mediators inside the barrier c)by binding to cytokine receptors associated with the vagus nerve and thereby signalling inflammatory changes in the brain via the nucleus tractus solitarius and hypothalamus [10,11]. Once in the brain, the proinflammatory cytokines activated both neuronal and non-neuronal (for example, the microglia, astrocytes and oligodendroglia) cells via the nuclear factor-kappa-beta (NF-kB) cascade in a similar manner to that occurring in the peripheral inflammatory response [12].

There is also evidence from clinical studies that peripherally administered cytokines can enter the brain. Thus the therapeutic administration of IFN to patients with hepatitis results in an increase in the cerebrospinal fluid (CSF) not only of IFN but also IL-6 and monocyte chemoattractant protein (MCP-1) [13]. In experimental studies it has been shown that MCP-1 activates microglia to release IL-1 and TNF [14] and as the microglia are the primary source of proinflammmatory cytokines in the brain this could be an important means whereby peripheral inflammatory mediators activate the inflammatory response in the brain. In addition, the proinflammatory cytokines modulate the release of biogenic amine neurotransmitters [15]. Recently much attention has been paid to the activation of the tryptophan-kynurenine pathway by these cytokines whereby tryptophan is shunted from the synthesis of serotonin to that of kynurenine. The importance of this pathway will be discussed in more detail later and clearly this is an important mechanism whereby serotonergic function is decreased in depression. The activity of the dopaminergic system is also reduced in response to inflammation. For example, IFN reduces the synthesis of dopamine by decreasing the concentration of the co-factor tetrahydrobiopterin (BH4), thereby reducing the synthesis of dihydroxyphenylalanine (DOPA), the immediate precursor of dopamine, from tyrosine [16]. As IFN increases the synthesis of nitric oxide by activating the BH4 dependent enzyme nitric oxide synthase in the microglia it seems likely that the reduction in dopaminergic function is linked to the increase in nitric oxide. This gaseous neurotransmitter is known to activate the glutamatergic system which, when this exceeds physiologically limits, enhances apoptosis and neurodegeneration [15,16].

Cytokines, and their signalling pathways, have been shown to enhance the re-uptake of monoamine neurotransmitters and thereby reduce their functionally important inter-synaptic concentrations in the brain [16,17]. For example,IL-1 and TNF have been shown to activate the serotonin transporter on neurons by stimulating the p38 mitogen activated protein kinase pathway [17]

In addition to the modulation of neurotransmitter function, proinflammatory cytokines contribute to the major symptoms of depression by activating the HPA axis by increasing the release of CRF, thereby contributing to hypercortisolaemia, a feature of major depression [18,19,20]. The mechanism whereby the cytokines induce hypercortisolaemia involves a decreased sensitivity of the glucocorticoid receptors thereby leading to glucocorticoid resistance; both the brain and the peripheral receptors become insensitive to glucocorticoid activation. The precise mechanism whereby the proinflammatory cytokines cause glucocorticoid receptor insensitivity is uncertain but it is known that the cytokines activate the inflammatory cascade. Thus the NF-kB, p38MAPK and the 5-STATS (signal transducer and activator of transcription 5) pathway is activated and leads to a disruption of the translocation of glucocorticoid receptors from the cytoplasm to the nucleus (21), thereby decreasing the active form of the receptor. While it would appear that glucocorticoid receptor resistance is correlated with the increase in the serum concentration of the proinflammatory cytokines, it seems unlikely that glucocorticoid resistance is directly related to the psychopathology of depression. Thus an increase in proinflammatory cytokines leading to glucocorticoid resistance also occurs in nondepressed individuals without any major change in the mood state [22]. However, such observations do throw light on the fact that many aspects of cellular and humoral immunity are not suppressed in patients with major depression despite the elevation of the plasma glucocorticoid concentration that is a common feature of the disorder."

"An important conceptual shift in the possible cause of depression has occurred recently with the discovery that inflammation plays a crucial role in the psychopathology of the disorder. However, as major depression is often accompanied by inflammatory diseases (such as irritable bowel syndrome, type 2 diabetes, arthritis and autoimmune disorders) that can activate the peripheral and central inflammatory response, it is possible that such inflammatory disorders initiate the inflammatory changes that precipitate depression. Although this is plausible, it is evident that inflammation also occurs in depressed patients who are not suffering from concurrent inflammatory disorders. Thus the increased vulnerability of depressed patients to psychosocial stress is probably the key factor that leads to the activation of the immune and endocrine axes in depression. It is known, for example, that even the relatively mild acute stress of public speaking causes an increase in NF-kB activity, a key element in the induction of the inflammatory cascade [23]. In this regard, it is also known that patients with major depression frequently show an enhanced responsiveness of IL-6 and NF-kB to an antigen challenge [24]. However, chronic stress, as experienced by caregivers or individual subject to marital discord but who are not suffering from depression also show an increase in plasma C-reactive protein, IL-6 and other inflammatory mediators [24,25]. Whatever the cause, such changes appear to be associated with activation of the microglia thereby suggestion that the inflammatory changes are also occurring in the brain [26].

The mechanism whereby psychological stress influences both the peripheral and central inflammatory cascade is co-ordinated by the autonomic nervous system. Thus the release of noradrenaline and adrenaline following the activation of the sympathetic system results in the activation of both alpha and beta adrenoceptors on immune cells thereby initiating the release of proinflammatory cytokines, via the activation of the NF-kB cascade, particularly on macrophages and monocytes in peripheral blood; antagonists of these adrenoceptors block the stress induced rise in these cytokines [27]. Conversely stimulation of the parasympathetic system has the opposite effect on the stress induced inflammatory response. Thus stimulation of the vagus nerve results in release of acetylcholine that activates the alpha-7 sub-unit on nicotinic receptors thereby reduces the activation of NF-kB [28]. It is possible that the anti-depressant-like action of vagal nerve stimulation, occasionally used to treat resistant depression, is associated with such an anti-inflammatory action.

The question arises why should inflammation occur in depressed patients despite the frequently observed increase in glucocortioids? The most parsimonious explanation is that glucocorticoid receptor resistance in the brain and periphery contribute to the lack of suppression of most types of immune cells with the possible exception of the natural killer cells. One possible explanation is that the stress induced increase in the sympathetic nervous system, combined with steroid resistance, leads to the activation of the microglia in the brain, and macrophages and monocytes in the periphery, thereby leading to the inflammatory state."
31 years old. POIS since puberty. Cognitive and physical symptoms.

G-man

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Re: Prevention and relief with plant sterols and sterolins (Moducare)
« Reply #42 on: February 05, 2015, 11:39:09 PM »
Continued from the previous post

"Of the numerous neurotransmitters that have been postulated to be dysfunctional in major depression, serotonin has been widely implicated for its contributory role in the symptoms of the disorder (sleep disturbance, depressed mood, anorexia, loss of libido and anxiety). Serotonin modulates the stress axis by activating the corticotrophin releasing factor pathways in the para ventricular nucleus thereby increasing the release of adrenocorticotrophic hormone from the anterior pituitary gland [29] There is a close relationship between the plasma cortisol concentration and the serotonergic system. Thus the stress induced rise in cortical is associated with an increased turnover of serotonin, a change that is linked to the stimulation of the rate limiting enzyme, tryptophan hydroxylase, in the pathway leading to the synthesis of serotonin from tryptophan [30]. Chronic stress that results in a sustained rise in cortisol has the opposite effect and sertotonin release is decreased. This is associated with the glucocorticoid activation of tryptophan dioxygenase in the liver whereby tryptophan is diverted from serotonin synthesis down the tryptophan-kynurenine pathway [31].

The increase in anxiety, and the impairment if adaptation to chronic stress that has been observed in both animals and man can be explained by the changes in the functional activity of the somatodendritic 5HT 1A receptors located on the median raphe nucleus and the hippocampus [32]. Experimental studies have shown that rats raised in a stressful, overcrowded environment show an increase in anxiety which is correlated with a decrease in the functional activity of the 5HT1A receptors. These receptors are influenced by the mineralocorticoid receptors that inhibit the 5HT1A receptor activity under conditions of chronic stress [33] In contrast to the 5HT1A receptors, the 5HT2 receptors are activated by chronic stress [34] while the 5HT1B receptors, that act as autoreceptors and thereby control the release of the transmitter, are activated by chronic stress [35]. Thus the stress induced changes in the circulating glucocorticoids can help to explain the decrease in the functional activity of the serotonergic system in depression."

...

"The emphasis in this review is on the adverse effects of the proinflammatory cytokines that, in pathological concentrations in the brain and periphery, are likely to cause cellular injury. However, it must be remembered that at physiological concentrations, these same cytokines provide trophic support for neurons, enhance neurogenesis and contribute to normal cognitive function [39]. Such effects are severely compromised when the cytokines are present in pathological concentrations and result in changes that are important in the psychopathology of depression. Thus in major depression, the prolonged activation of the inflammatory network in the brain results in a decrease in neurotrophins, leading to reduced neuronal repair, a decrease in neurogenesis, and an increased activation of the glutamatergic pathway that contributes to neuronal apoptosis, oxidative stress and the induction of apoptosis in astrocytes and oligodendrocytes [40,41,42,43].

In addition to the proinflammatory cytokines, nitric oxide and the glucocorticoids, glutamate plays a crucial role in the pathological processes that are associated with depression. The proinflammatory cytokines, and inflammatory mediators such as nitric oxide, increase glutamate release and decrease the expression of glutamate transporters on astrocytes and oligodendroglia thereby decreasing glutamate reuptake and enhancing the inter-synaptic concentration [44].

Stimulation of the extra-synaptic N-methyl-D-aspartate (NMDA) glutamate receptor not only causes excitotoxic damage to the neurons and astrocytes but also results in a decrease in synthesis of brain derived neurotrophic factor (BDNF), a key neurotrophic factor governing neuronal repair [45]. To add to the potential neurotoxic changes, IL-1 and TNF, that are generally raised in depression, trigger the release of reactive oxygen and nitrogen species from activated microglia and astrocytes; these are toxic to both neurons and oligodendroglia [46,47]. The net result of these changes is a loss of astrocytes and oligodendroglia, and neuronal apoptosis particularly in the subgenual prefrontal cortex, the amygdala and the hippocampus, brain regions that are thought to be crucially involved in the genesis of the symptoms of depression.[48].

The question now arises regarding the possible link between the neurotoxic effects of the proinflammatory cytokines, excess glutamate and the tryptophan-kynurenine pathway that, in depression, produces neurotoxic end-products that contribute to neurodegeneration in depression. Tryptophan is metabolised through two main pathways, one of which leads to the synthesis of serotonin and the other to kynurenine and kynurenic acid. In the latter pathway, tryptophan is metabolised by indoleamine 2,3 dioxygenase (IDO), an enzyme that is quite widely distributed in peripheral tissues and the brain, and by tryptophan 2,3 dioxygenase (TDO) that is primarily located in the liver [49]. IDO is activated by proinflammatory cytokines while TDO is activated by glucocorticoids. As both the cytokines and cortisol are raised in major depression, it is not surprising to find that the tryptophan-kynurenine pathway is increased [49,50]. Anti-inflammatory cytokines reduce the activity of this pathway [51]. There are two main pathways that lead to the metabolism of tryptophan following the formation of kynurenine. Kynurenine hydroxylase metabolises kynurenine first to 3-hydroxykynurenine and then to 3-hydroxyanthranilic acid and quinolinic acid. This pathway is increased in depression and dementia [49,50]. In glia and neurons 3-hydroxykynurenine increases the formation of reactive oxygen species while quinolinic acid activates NMDA glutamate receptors and thereby enhances apoptosis. By contrast kynurenine can be metabolised by kynurenine aminotransferase to for the neuroprotective end product, kynurenic acid, an antagonist of NMDA receptors [51]. In the brain,the metabolism of tryptophan by IDO occurs both in the microglia and astrocytes [52]. The microglia synthesise both 3-hydroxyanthranilic acid and quinolinic acid while the astrocytes produce mainly kynurenic acid. Astrocytes also metabolise quinolinic acid and therefore under physiological conditions can reduce the impact of the neurotoxins [53]. In chronic depression however, the activated microglia produce an excess of the neurotoxin that cannot be adequately metabolised by the astrocytes. Furthermore quinolinic acid can cause apoptosis of the astrocytes. This results in a reduction in the metabolic and physical buffer to the neurons that is usually provided by the astrocytes and thereby further exposes the neurons to the neurodegenerative actions of quinolinic acid [54].

The clinical evidence supporting the hypothesis that the tryptophan-kynurenine pathway is activated comes from two major studies. Wichers and coworkers [55] showed that the concentration of kynurenic acid was reduced in patients being treated with IFN for the treatment of hepatitis while Myint and colleagues [56] reported evidence that components of the neurodegerative pathway was increased in the blood of depressed patients before antidepressant treatment. Effective treatment for 8 weeks only partially reversed these changes in patients being treated for their first major episode of depression but had no effect in those patients who had suffered several episodes. This suggests that more permanent changes may occur in the brain of those with a chronic depression.

The structural changes observed in the brain of patients with chronic depression lends support to the neurodegenerative hypothesis of depression [57]. It is known that there is a shrinkage of the hippocampus in patients with major depression [58] and a decrease in the number of astrocytes and a neuronal loss in the prefrontal cortex [59] and in the striatum. Such changes could be the consequence of chronic low grade inflammation in which the proinflammatory cytokines, nitric oxide, prostaglandin E2 and other inflammatory mediators play key roles; the cytokines are known to induce the cyclo-oxygenase and nitric oxide sythase pathways in the brain and thereby increase the inflammatory insult [60]. The inhibition of neurotrophin synthesis in the brain by glucocorticoids [61], and the neurotoxic action of quinolinic acid, add further to the impact of the inflammatory changes."
31 years old. POIS since puberty. Cognitive and physical symptoms.

Quantum

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Re: Prevention and relief with plant sterols and sterolins (Moducare)
« Reply #43 on: March 06, 2021, 06:10:20 PM »
I am posting a follow up on my Moducare use in POIS.  This thread dates back to the first months I had found poiscenter.   You can read my update in its context at https://poiscenter.com/forums/index.php?topic=3717.msg39648#msg39648 .

here is a copy and paste of it:
"Hi Journey,  here is some info about this Th1 and Th2 balance:
"Too little TH1 activity and the immune system can not fight off virus or cancer, whilst too much TH2 activity and the immune system will stop recognising self tissue as self and damage its own body (an auto immune reaction). A balanced T helper cell activity is essential for optimum health." ( from https://dennisthechemist.blogspot.com/2011/11/moducare-and-me.html  , interesting and simple article to understand the basics of the Th1 - Th2 system)


Interestingly enough, Moducare will help either way.  It helps raise Th1 when too low and helps lower Th2 when too high.

Recently, I have used Moducare in the context of a couple of unexpected NE.  2 Capsules right after, when I woke up, and again the following day, a few other doses.  I was amazed at how well it works for me.  Back in 2014, when I developed my pre-pack composition, I remember I put it aside because of its rather higher cost than other supplements, but I already knew it was very effective for me.  Through the years, I kept it for treating cold and flu, and allergy symptoms.  Now I probably have developed more kindness for myself than back then :)   I remembered having tested it positively in POIS, and now I "allow" myself to use Moducare more often, including when I have some POIS residual symptoms.  By not using it fo POIS for about 6 years now, I had forgotten how much it is effective to get rid of any residual fatigue and any other residual POIS symptoms, including emotional ones ( irritability, mood swings, ...).   "
« Last Edit: March 06, 2021, 06:15:47 PM by Quantum »
You are 100% responsible for what you do with anything I post on this forum and of any consequence it could have for you.  Forum rule: ""Do not use POISCenter as a substitute for, or to give, medical advice" Read the remaining part at http://poiscenter.com/forums/index.php?topic=1.msg10259#msg10259