Alchemica Posted September 17, 2018 (edited) How do you modulate your serotonin system with dietary factors? I wanted to try and address persistent issues at the most fundamental dietary level possible - amino acids, vitamins. I tried some challenge doses with tyrosine and tryptophan and the later seemed to provide the most robust improvements. I keep on top of B-vitamins but assumed tryptophan in dietary protein was going to be enough... I've been abstinent from deleterious things for a long time now but it didn't mean health was improving. I couldn't shift a worsening phenotype of persistent emotional and mood dysregulation, cognitive decline, multiple night time awakenings and poor sleep quality, uncharacteristic uncontrollable verbal aggression (to the point of coprolalia), impulsiveness, intrusive thoughts, obsessiveness and plain dysphoria. SSRIs alone were not getting at the issue sufficiently. Diet, exercise and meaningful activity wasn't stopping the roller-coaster. Studies have found disturbances of tryptophan metabolism and their association with depression in alcoholics. Particularly, a decreased tryptophan ratio to other amino acids competing with tryptophan for brain entry has been investigated - diminished supply of tryptophan would lead to serotonin deficiency and thus contribute to depression in alcoholics Depressed alcoholics had significantly decreased ratios of plasma tryptophan to amino acids sharing with it the same transport carrier into the brain (tryptophan ratio). This ratio has been shown to predict the brain serotonin concentration. It is not presently known whether amino acid modifications disappear after a period of abstinence or persist [1]. Patients who had exhibited violent behavior were observed to have tryptophan ratios lower than patients with no history of violence. Research has demonstrated a robust response to increasing plasma Trp/LNAA ratio, stimulating a significant affective response. Unexpectedly Trp supplementation not only improved central serotonergic functioning but improved the profile of tryptophan metabolism [2]. [1] http://grantome.com/grant/NIH/R01-AA006510-02 [2] https://patentimages.storage.googleapis.com/50/94/8b/2fef42545c61d4/WO2005049012A2.pdf Using the amino acids is not just addressing pathology but providing some vital things: A source of believable hope, when things feel hopeless A source of day-to-day stability and connection to something when other sources of connection are non-existent or volatile A sense of being in control, when things feel out of control A secure quasi 'attachment relationship' to something when these might not elsewhere exist A safe displacement onto healthier behaviours for residual impulsivity and craving A placebo effect synergistic with added active effects. Placebo effects themselves can be potent medicine, as seen in many illnesses, from depression to Parkinson's. Sure it's better to find these things in other ways but it's often the most stable, permanent connection in times of illness and volatility one can find In recovery: “Glutaminergic-Dopaminergic Optimization Complex Therapy”, has been well-researched in many clinical trials and shown to provide gentle activation of dopamine across the brain reward circuitry in abstinence. Additionally, significant increases in resting state functional connectivity have been demonstrated in human and animal models using state of the art resting state fMRI measurements [1] Amino acid based therapies have led to: Improved Physical and BESS (behavioural, emotional, social and spiritual) Scores Reduced craving, relapse rates and enhanced recovery Stress reduction lead to improved sleep, enhanced energy, and improved focus and performance, reduced appetite, loss of unwanted weight, decreased body inches, and enhanced well-being Cognitive processing speeds were enhanced Significant results were observed for weight loss, sugar craving reduction, appetite suppression, snack reduction, reduction of late night eating, increased energy Research is needed regarding the potential for return of well-being in recovery by the gentle induction of “dopamine homeostasis;” balancing serotonergic, endorphinergic, cannabinergic, glutaminergic, dopaminergic mechanisms and restoring healthy brain function and connectivity. While I'm just using simple aminos and vitamins, one such version that has been extensively researched is KB220Z which is composed of the following ingredients: 10 mg (500%) vitamin B6, 15 mg (1,033% of daily value) thiamine, 200 mcg (166%) chromium poly nicotinate, and a fixed dose of synaptose. Synaptose is a combination of amino acids and herbs. The amino acids include L-tyrosine, DL-phenylalanine, L-glutamine, and 5-hydroxytryptophan. The herbs include passionflower extract and a complex containing astragalus, arabinogalactans, N-acetylglucosamine, aloe vera, white pine bark extract, frankincense resin, Spirulina, Rhodiola [1] https://dx.doi.org/10.1080%2F10826084.2016.1244551 What if the serotonergic dimension needs more urgent addressing? I tried L-methylfolate 15mg/day (+B12 1mg) with slight improvements for a short time, then also added some tryptophan [1] to the diet. A few days into adding the Trp and the coprolalia waned, emotional regulation started to return. I started to get malleable non-intrusive thinking again. Mood started to improve. See what happens longer term Folate for Depression, Schizophrenia and Dementia: Folate supplementation may be beneficial for severe mental health problems Folate deficiency seems to be an important contributor for the onset and progression of neuropsychiatric diseases [2]. L-methylfolate addresses hyperhomocysteinemia, lower methylation reactions and tetrahydrobiopterin levels [3]. Brain folate abnormalities causes diminished production and availability of tetrahydrobiopterin (BH4) which is a critical cofactor for the rate-limiting enzymes involved in the synthesis of the monoamine neurotransmitters and may be targeted by L-methylfolate. L-methylfolate should cause, in an over-simplistic framework: -Activation of tryptophan hydroxylase initiates a cascade that leads to the synthesis of serotonin, and -Activation of tyrosine hydroxylase initiates a cascade that leads to the synthesis of dopamine and norepinephrine [1] http://journals.sagepub.com/doi/abs/10.1177/0269881111430744 [2] https://www.ncbi.nlm.nih.gov/pubmed/25939915 [3] https://www.ncbi.nlm.nih.gov/pubmed/27068282 Why L-methylfolate? Many users find it quite effective - some users get quite rapid responses "Within 1 day, I felt like my internal motor that had been idling along at a 5 out of 10 had been turned up to a 10 for the first time in a long time. I had more energy, clearer thoughts, happier disposition..." "I felt better the first day. I feel like normal people feel. I have hope, motivation, freedom. I am completely happy." "Within just days of my first dose, I could fell a huge, positive difference. My mind and speech were clearer, my anxiety was nearly unrecognizable, and I was just plain happy." "...my lows vanished within first week on 15mg/day." "Within one week of taking L-methylfolate, I had absolutely NO anxiety. It was so quiet in my soul that I almost felt anxiety about not having anxiety! It was foreign to me; the steady drip, drip, drip of adrenalin rushing through my system was shut off." "Within 10 days, I felt more alive, motivated, energetic, and at peace then I had EVER felt in my life. " 15 mg eight days ago and I feel absolutely wonderful. Mood is great, anxiety has improved significantly, and I feel so peaceful. My energy level is up, and I feel hopeful and full of life again. I am so relieved and happy I could cry." I am able to finally really smile and laugh. I have not been able to find humor in things for years. I have more of a sense of well being I have more serenity I have an increased amount of time I feel better emotionally and mentally There is some support for the efficacy of both standard folic acid and L-methylfolate as an augmentation agent for depression [1]. The lowest dose of MTHF studied in depression to augment antidepressant treatment is 7.5 mg, roughly equivalent to 52 mg of folic acid. Synthesis of the monoamine neurotransmitters serotonin, dopamine, and norepinephrine is regulated by L-methylfolate, which can cross the blood brain barrier. "Adjunctive L-methylfolate at 15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs" [2]. It shows promise against negative symptoms in psychotic illness [3]. "Clinical improvement in depressed patients treated with an SSRI and l-methylfolate (0.5 to 1 mg) was 30 percent greater than that in matched patients treated with an SSRI only. A systematic review of controlled studies (total N = 247) concluded that folate augmentation (1 to 15 mg per day) enhanced the efficacy of conventional antidepressants." "Does folate supplementation relieve symptoms of depression? A ten-week trial of 127 participants compared 0.5 mg/day folic acid (standard folate) augmentation of fluoxetine to placebo augmentation, and found that folic acid significantly outperformed placebo in terms of treatment response rate (38% vs. 18%) and overall improvement on the Hamilton Depression Rating Scale. However, the advantages for folic acid were not seen until ten weeks into treatment. In a smaller trial, patients with depression or schizophrenia were given either 15 mg methylfolate (equivalent of 7.5 mg L-methylfolate) or placebo in addition to their existing medication regimen. Though hampered by a small sample size (24 depressed patients and 17 patients with schizophrenia), there was a statistically significant benefit on a general clinical outcome scale and there were trends toward a significant benefit on other outcome measures in the six-month study" Administration of MTHF may have significant advantages over administration of folic acid to augment antidepressants in depressed patients who do not respond adequately to their antidepressant treatment. Such patients may or may not be folate deficient, may or may not have the inefficient form of the genotype. "Biomarkers associated with inflammation or metabolism (higher BMI) and genomic markers associated with L-methylfolate synthesis and metabolism may identify patients with SSRI-resistant depression who are responsive to adjunctive therapy with L-methylfolate" [4]. "Patients with schizophrenia who take daily folic acid in the form of methylfolate 15 mg together with an antipsychotic may have fewer positive symptoms (e.g. hallucinations and delusions) and fewer negative psychotic symptoms (paucity of thought, social withdrawal) and may respond more rapidly" [5] [1] https://pro.psychcentral.com/l-methylfolate-for-depression-the-real-deal/ [2] https://www.ncbi.nlm.nih.gov/pubmed/23212058 [3] http://www.schizophreniaforum.org/news/l-methylfolate-shows-promise-against-negative-symptoms-schizophrenia [4] https://www.ncbi.nlm.nih.gov/pubmed/24813065 [5] https://www.psychologytoday.com/us/blog/integrative-mental-health-care/201709/folate-depression-schizophrenia-and-dementia Addressing homocysteine and potential B9/B12 deficiencies While I keep on top of B-vitamins generally... Stress can increase homocysteine levels (HCy). Higher levels of hostility were associated with higher levels of homocysteine [1]. People high in hostility are known to report more life stress, it is possible that homocysteine concentrations are elevated among these individuals due to increased stress [2]. Elevated levels of homocysteine have been associated with major depressive illness (and positively correlated with anger and length of depressive episode), bipolar disorder (both during manic and depressive episodes and in euthymic state) and various other mental conditions. "Studies of subjects with a wide range of cognitive functions showed increased plasma Hcy and decreased serum folate and enzymatic cofactors involved in methionine and Hcy metabolism are associated with the risk of cognitive dysfunction" Supplemental use of these vitamins has shown a slowing cognitive decline and also improvement in clinical status in patients with cognitive impairment, particularly in those with high baseline levels of serum Hcy [3]. A high circulating concentration of homocysteine has been implicated as a risk factor for Alzheimer's Disease and its prodromal stage, mild cognitive impairment. Cognitive and psychosocial impairment has been associated with increased levels of homocysteine [4]. While not a specific marker for schizophrenia, hyperhomocysteinemia occurred in our schizophrenia patients with poor social and relational functioning [5]. Elevations of serum homocysteine levels are a consistent finding in addictions. Hyperhomocysteinemia could enhance the substance consumption increasing the severity of craving in a circular self reinforcing mechanism. [6,7] MTHFR variants and smoking behaviour were associated with homocysteine plasma levels [8] Folate deficiency is associated with depression, attention issues, and other neuropsychiatric disorders, along with irritability and behavioural problems. Cerebral folate deficiency has been linked to self-injurious behaviour. In ASD, "In clinic I have certainly seen some very beneficial effects of using the active forms of folate in ASD" [9] Inflammation induced by by low folate concentrations can significantly be attenuated through treatment with appropriate supplementation and result in cognitive function improvement and decrease of peripheral inflammatory cytokine levels B12 deficiency has been "linked to agitation, irritability, negativism, confusion, disorientation, amnesia, impaired concentration and attention and insomnia; while psychiatric disorders that may be diagnosed in patients having vitamin B12 deficiency include depression, bipolar disorder, panic disorder, psychosis, phobias and dementia". B12 deficiency has presented in younger patients with “irritability, regressive behaviour, apathy, crying and truancy” [1] https://news.osu.edu/hostility-anger-linked-to-chemical-that-may-cause-heart-disease/ [2] https://www.ncbi.nlm.nih.gov/pubmed/14724053. [3] https://www.ncbi.nlm.nih.gov/pubmed/29936555 [4] https://www.ncbi.nlm.nih.gov/pubmed/29306698 [5] https://www.ncbi.nlm.nih.gov/pubmed/26017629 [6] https://www.ncbi.nlm.nih.gov/pubmed/28527647 [7] https://www.ncbi.nlm.nih.gov/pubmed/26885351 [8] https://www.ncbi.nlm.nih.gov/pubmed/23285280 [9] http://www.allnaturaladvantage.com.au/home/wp-content/uploads/2014/11/Cerebral-Folate-Deficiency.pdf Addressing serotonergic aspects The emotional dysregulation was intense. It seemed to be hypothetically a very 5-HT deficient state Both fear/terror and anger/rage are here further assumed to be low-serotonergic. Aggression has also been coupled to serotonergic deficit in many studies, supporting the placement of anger/rage on the low-serotonergic side A first approach would involve the administration of tryptophan and/or BH4. Lack of tryptophan in the diet has been linked to decreases in tissue tryptophan and in brain serotonin - changes in tryptophan availability have a direct impact on the rate of 5-HT synthesis Tryptophan enriched diets in animal models have led to increased prefrontal activation, these results seem to suggest that activation of the PFC could be related to a decrease in anxiety/diminishing amygdalar activity and to decrease in depression-related symptoms L-tryptophan has shown efficacy as an isolated substance in the treatment of depressed patients (it lifted the mood of participants and affected the function of brain regions known to be associated with mood regulation), addition of tryptophan to fluoxetine was associated with a greater improvement within the first week of treatment. It also lessened the fluoxetine-induced decrements in slow wave sleep. There were no cases of serious toxicity of the combination; it was very well tolerated overall [1]. Serotonin syndrome resulting from augmentation of antidepressants with L-tryptophan is ‘rare’ It has found use in OCD as an augmentation strategy [2] L-tryptophan was found to be a well tolerated and useful adjunct and standalone antidepressive agent in treatment-resistant unipolar depressed borderline personality disorder patients, with positive effects on sleep, suicidality and social engagement. [3] [1] https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/11022398/ [2] https://www.ncbi.nlm.nih.gov/pubmed/9393391 [3] https://www.sciencedirect.com/science/article/pii/S221296261500036X Trp as a dietary manipulation "Impulsive, violent and suicidal behaviours have repeatedly been shown to be associated with a reduction in serotonergic activity in the central nervous system. Tryptophan supplementation may be most effective in reducing aggression during times of stress. Tryptophan, an essential amino acid, is the dietary precursor to serotonin, and several lines of evidence have suggested that the amount of tryptophan in the diet relates closely to aggressive behavior. For example, rats given a diet almost lacking in tryptophan develop aggressive behavior In a group of depressed alcoholics, those with a history of aggression, including suicide attempts, also had the lowest tryptophan ratios When hospitalized male schizophrenics were given tryptophan, only those patients with high levels of hostility and a high lifetime frequency of aggressive incidents benefited; these patients showed a lessening of hostility and depression, a reduction in ward incidents and improvement on a standardized psychiatric rating scale." Note: A diet high in Trp, but with a large amount of LNAAs (leucine, isoleucine, tyrosine, phenylalanine, and valine), will not result in higher brain Trp levels, and may even decrease Trp uptake into the brain. An intervention rich in Trp relative to other LNAAs (including is needed in order to boost uptake of Trp, and consequently serotonin production, in the brain. It may be more difficult for the prefrontal cortex to control negative emotional responses that are generated within the amygdala under low serotonin, meaning Trp may help [1] Low tryptophan levels may significantly affect the mood and may contribute to anti-social, aggressive and impulsive behaviours [2] Tryptophan metabolism is disturbed in abstinence Experimental lowering of serotonin (5-HT) neurotransmission by acute tryptophan depletion (ATD) induces a transient depressed mood in 50–60% of patients treated with a selective serotonin reuptake inhibitor (SSRI) who are in remission from depression [3]. It has been claimed by some that simple dietary manipulation is not an effective method to increase brain Trp and 5-HT. The effect of an SSRI on extracellular 5-HT are dependent on the nutritional availability of Trp. Moreover, increased availability of TRP affects behaviour in a manner similar to SSRI administration. While caution is advised, it's being explored as an augmentation strategy [4] "...nutritional factors play an important role in the biosynthesis of 5-HT. Increasing 5-HT levels by increasing the availability of TRP might augment the therapeutic efficacy of SSRIs, whereas malnutrition may render patients refractory to SSRI treatment.” Studies suggest long-term effects of dietary Trp on stress responsiveness Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation in OCD. "Successful selective serotonin reuptake inhibitor treatment of obsessive-compulsive disorder may involve the ability of serotonin to switch habitual responding to goal-directed behaviour." and it has been proposed tryptophan or 5-HTP may augment the effectiveness of antidepressants. Trp supplementation seems to improve control over social behaviour in patients and individuals suffering from disorders or behaviours associated with dysfunctions in serotonergic functioning - in healthy humans supplementation seems to promote social behaviour [5]. Review: Effects of tryptophan loading on human cognition, mood, and sleep [1] https://www.cam.ac.uk/research/news/serotonin-levels-affect-the-brain’s-response-to-anger [2] https://www.salubrainous.com/tryptophan-for-alcoholism/ [3] https://www.sciencedirect.com/science/article/pii/S0165032705000182 [4] https://link.springer.com/article/10.1007/s00213-003-1632-6 [5] https://doi.org/10.1016/j.neubiorev.2016.02.022 Part of the fun with effectively bolstering serotonergic activity is that positive beliefs come on line (or feel positively amendable), what were heavy cognitive self-referential processes taper down there's a socio-emotional dimension that comes on line and cognitive/behavioural flexibility bolsters. Studies show that the relationship between the activation of serotonin and subsequent behaviour is highly dependent on the belief about the circumstances [1] Self-referential processing is a key cognitive process, associated with the serotonergic system and the default mode network (DMN). "Typically, depressed individuals endorse more negative adjectives as self-referential than non-depressed individuals. This bias in self-referential processing is also present in individuals who have remitted depression, suggesting that negative cognitive biases persist even when symptoms are no longer evident." "Analytical self-focused rumination (thinking analytically about self and symptoms) is maladaptive - This cognitive style is associated with overgeneral autobiographical memory, global negative self-judgments, greater negative future thinking, and dysphoria." It appears to reflect DMN connectivity which can be modulated by TRP [3] [1] https://www.eurekalert.org/pub_releases/2018-06/oios-wfi053018.php [2] https://www.sciencedirect.com/science/article/pii/S016801021002835X There are a few 'side effects' to Trp While "involvement of 5-HT in rewarding and aversive processing, hedonic experience, mood and higher cognitive functions such as consciousness or self reflection are undisputed" and there seems to be a good level of "contentedness" and mood/emotional regulation... Manipulations of serotonergic tone affect reward [1] and decision making [2]. Depleted states cause one to be significantly more perseverative over choices and acutely significantly less sensitive to reward (lower reward magnitude) For me, the impulsive reward chasing loops start to seemingly undergo some changes (serotonin has been proposed as a possible encoder of reward and facilitator of reward extinction): you go from impulsive action to greater conscious choice but it doesn't feel as rewarding to do things. It's a little blunting. So those healthy addictions, for me gardening and daily walking, start to feel more effort-driven than impulse driven and require more effort in. If you're not careful, you can become content with inaction. Depletion of 5-HT enhances behavioural and brain responsiveness to aversive signals, while disinhibiting previously rewarded but now aversive behaviours. [3] You start to seemingly have a layer of higher order self-reflection come in. You want better choices. It has been proposed "5-HT encodes beneficialness, and may signal motivation to either maintain or switch current behaviour, for example displayed by 5-HT’s role in facilitating patience for future rewards" [1] https://www.frontiersin.org/articles/10.3389/fnhum.2017.00484/full [2] http://www.jneurosci.org/content/32/17/5833 [3] https://www.ncbi.nlm.nih.gov/pubmed/18069045 Edited September 18, 2018 by Alchemica 4 Share this post Link to post Share on other sites
tarenna Posted September 19, 2018 Welcome back A.. 1 Share this post Link to post Share on other sites
Alchemica Posted September 20, 2018 (edited) The recent dietary modification has given me baseline stable state where it feels feasible to attempt simple meditations, started that and try and incorporate that each morning, whereas before the dysregulation was something I couldn't at all over-ride. In SUDs, there is a brain-state shift from a hippocampal and PFC- mediated regulatory state to a more primitive and dysregulated amygdala and insula-mediated state underlying emotion dysregulation Few things I've noticed: Trp influences behaviour along the agonistic–affiliative axis, it regulates the tone of interactions along the axis that runs from agreeable to quarrelsome to overt aggression. Tryptophan - promotes prosocial behaviour. - promotes interpersonal trust. - causes greater sharing and helpfulness, greater perspective taking and emotion recognition. - improves control over antisocial behaviour - It allows regulation of aggression and positive social interactions, as well as emotional processing Serotonergic signalling impacts the two-way interaction between each of the following pairs: mood and social behaviour, mood and cognition, social behaviour and cognition and increases prosocial behaviours - Enhanced serotonergic function might promote effortful control over underlying action tendencies - Enhancing serotonergic function should decrease reliance on habitual, reflexive forms of self-regulation and increase the use of effortful, reflective forms of behaviour regulation - Enhanced 5-HT leads to blunted evaluative responses to both positive and negative stimuli Manipulations of serotonergic tone affect reward [1] and decision making [2]. Depleted states cause one to be significantly more perseverative over choices and (acutely) significantly less sensitive to reward (lower reward magnitude) For me, the impulsive reward chasing loops start to seemingly undergo some changes (serotonin has been proposed as a possible encoder of reward and facilitator of reward extinction): you go from impulsive action to greater conscious choice but it doesn't feel as impulsively rewarding to do things. It feels a little blunting. So those healthy addictions, for me gardening and daily walking, start to feel more effort-driven than impulse driven and require more effort in. If you're not careful, you can become content with inaction. Depletion of 5-HT enhances behavioural and brain responsiveness to aversive signals, while disinhibiting previously rewarded but now aversive behaviours [3]. Dysfunction by the serotonergic system in impulse control disorders reflect inhibitory impairment of the prefrontal cortex [4]. You want 'better'. It has been proposed "5-HT encodes beneficialness, and may signal motivation to either maintain or switch current behaviour, for example displayed by 5-HT’s role in facilitating patience for future rewards" [1] https://www.frontiersin.org/articles/…/fnhum.2017.00484/full [2] http://www.jneurosci.org/content/32/17/5833 [3] https://www.ncbi.nlm.nih.gov/pubmed/18069045 [4] http://europepmc.org/articles/PMC4117279 Imagine, after a long time of not knowing/feeling emotions or self-regulating them, you are now unable to avoid the blunt edges of tough emotions which are, after so long, alien influences. Sadness, anger, disappointment, frustration, boredom, annoyance, confusion, disgust, surprise, anxiety, guilt, shame, embarrassment. There is no more avoidance. Your escape route has gone. ‘Feeling all the feels’ is like being on a furious roller coaster, particularly when your emotional regulation route has always been psychopharmacological. There's not just the array of problems induced by self-medication but also over a decade of often supratherapeutic doses of potent psychotropics/ECT, including over neurodevelopmentally-sensitive timeframes when the prefrontal networks and skills in emotional regulation should have been developing. I'll attest that attempting meditation when all emotional regulation is in tatters and you have pure negative affect is plain frustrating, studies show that greater intact emotional regulation when meditating produces more benefits in affect regulation You can use attentional bias modification: mindfully focus on their breath, or on emotions. Breathing meditation and emotion-focused meditation may constitute effective emotion regulation strategies to deal with negatively valenced emotional states [1] Short meditation [2] enhanced mood (i.e., total mood disturbance, anxiety, and fatigue), cognition (i.e., attention, working memory, and recognition memory), and improved the response to acute stress Simple 13 min meditation [they used Journey Meditation (http://www.journeymeditation.com/) for 8 weeks has been studied. 8 weeks of brief daily meditation relieves feelings of negativity by decreasing levels of mood disturbance. It exhibited a similar range of cognitive benefits as the effects previously reported following longer duration, more intense meditation training If you get through regulating and managing persistent negative emotion, you start to feel the good ones in all their glory too. All of the lovely positive emotions such as; satisfaction, joy, elation, excitement, love, contentment, gratitude, hope, amusement, inspiration, awe, interest. [1] https://www.ncbi.nlm.nih.gov/pubmed/30146138 [2] https://www.ncbi.nlm.nih.gov/pubmed/30153464 The world of emotions Key to this employment of equanimity to reduce emotional reactivity is the intentional cultivation of awareness towards emotional information. I was shutting down that world. "Limiting cognitive elaboration in favor of momentary awareness appears to reduce automatic negative self-evaluation, increase tolerance for negative affect and pain, and help to engender self-compassion and empathy in chronically dysphoric individuals" [1] - cognitive elaboration often automatically triggers negative self-judgments that cannot be voluntarily overridden "Dysregulation of fronto-limbic control regions may lead to maladaptive, ruminative, and egocentric attention contributing to depressive affect. In mood disorders, cognitive control appears to be impaired, there is compromised connectivity between the PFC and limbic regions such as the amygdala. Thus, activating PFC regions in efforts to reappraise negative feelings may backfire, bringing attention to focus on dysphoric mood without a commensurate reduction in the intensity of negative feelings." Instead, you begin observing, describing, acting with awareness, being nonreactive, and being nonjudging. When emotional information is consciously attended, you evoke less of an amygdala response and engaged greater prefrontal cortical resources. By deploying attentional resources to recruit a network that limits habitual elaboration and self-referential narrative "automatic recruitment of temporally-extended, self-referential narrative generation may undergo a form of neural extinction, restoring autonomy to the central executive system and freeing it from its habitual applications For me, some of the skills I'm trying to bolster are: 1. Acceptance of emotional responses (ACCEPTANCE) 2. Engaging in goal directed behavior (GOALS) 3. Impulse control (IMPULSE) 4. Emotional awareness (AWARENESS) 5. Emotion regulation strategies (STRATEGIES) Mindful emotion regulation can be construed as a process of ‘turning toward’ momentary experience - attention is positively directed towards present moment sensation, providing a non-conceptual and non-threatening focus for attention 6. Emotional clarity (CLARITY) Improving the self-regulation of attention might reduce the negative emotionality associated with ruminative thought patterns and the tendency to suppress thoughts, both of which have been associated with craving and relapse in addictive behaviours [2] The development of an attitude of acceptance (i.e. a nonjudging/nonattached view of experiences) could reduce negativity affectivity by reinforcing distress tolerance abilities in relation to several experiences (e.g. craving, stress, anxiety) [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303604/ [2] https://www.ncbi.nlm.nih.gov/pubmed/30216741 Tryptophan and ASD I always had strong affinity for serotonergics but addressing it at the dietary level is so much more sustainably promising for me than other approaches. Trp, B-vitamins and magnesium have been used. While radically boosting prosociality through empathogens is being researched for autism, I feel it often needs to be addressed at a more fundamental and sustainable level. A slow and steady, easily integratable and sustainable induction of mood, emotion and greater prosociality can seemingly be had through safer dietary serotonergic interventions. "Low brain tryptophan availability… could be one of the possible mechanisms involved in the alteration of serotonergic function in autism.” "Serotonergic abnormalities were reported in ASD. Research indicates that the reduced levels of serotonin are correlated with the occurrence of impulsive and aggressive behavior, fatigue, depression episodes, insomnia and increased sensitivity to pain. There is evidence that pharmacological treatment is aiming the reduction of the serotonergic neurotransmission results in worsening of autistic symptoms" [1] "Often, families observe that anxiety and subsequent frustration leading to aggression can be better controlled by administering this supplement on a daily basis. Likewise, more focus and attention may accompany administration of tryptophan" [2] It seems to have quite prominent socio-emotional qualities in the way I'm using it that have not really been researched in ASD "BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes." [3] Lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder. Lower 5-HT synthesis were hallmarks of AS [1] https://link.springer.com/article/10.1007/s11011-017-0045-x [2] http://www.theautismdoctor.com/tryptophan-to-treat-autism/ [3] https://www.ncbi.nlm.nih.gov/pubmed/30033880 It also targets another issue for me: Recent findings suggested the serotonin system may be an effective target for prevention and treatment of mild cognitive impairment “Now that we have more evidence that serotonin is a chemical that appears affected early in cognitive decline, we suspect that increasing serotonin function in the brain could prevent memory loss from getting worse and slow disease progression.” Researchers have tried with limited success to treat Alzheimer’s disease and cognitive impairment with antidepressants such as SSRIs What if it's as simple as tryptophan as a starter? I was skeptical about simple tryptophan, assuming it could worsen pathology through often noted disturbed tryptophan metabolism. L-Tryptophan (TrP) enriched diet protect against memory deficits during physiological aging 5-HT modulates BDNF mRNA levels. TrP significantly elevates the number of 5-HT immunoreactive fibers and this correlated with BDNF increase in the FC and hippocampal region "...enhanced TrP intake and the consequent increase in 5-HT neurotransmission may act as a modulator of BDNF system suggesting a possible mechanism for the protective role of serotonergic system on memory impairment occurring along normal aging process." [1] "data suggest that enhanced TrP intake, and in consequence a potential increase in 5-HT neurotransmission, might be beneficial in preventing age-related detrimental features by inhibition of hippocampal apoptosis." [2] https://www.healio.com/.../serotonin-may-play-important... [1] https://www.ncbi.nlm.nih.gov/pubmed/26444078 [2] https://www.ncbi.nlm.nih.gov/pubmed/27889579 Targeting alexithymia Working through spectrums of emotions and getting some quite pleasant positive ones for once. My emotional world has consistently much improved, as has the range of accessible emotions, I have to learn to put words to them more. Finally looking forward to the new place now that I'm not stuck with such negative unprocessed emotions over-riding me. I like this take. "Alexithymia, a personality trait involving difficulties in identifying and describing one’s own emotional feelings and an externally oriented or concrete thinking style, has been reported to be strongly associated with alcohol misuse" [1] "We argue that emotion processing deficits result in a diminished ability to put words to emotions, or articulate feelings, with the consequence that feelings cannot be acted on with goal directed behaviour, but are instead treated as undifferentiated emotion distress, prompting repetitive compulsive behaviours." In alexithymia, "Instead of dampening amgydaloid activity (and subsequent neuro-endocrine release) in order to identify and label emotion in order to cognitively process, alexythmics may do the opposite. They appear to increase amgydaloid and neuro-endocrine activity, which recruits more automatic, implicit and motoric regions in responding to affective stimuli. Emotion is thus not labelled as a resource to be cognitive processed but almost treated in a compulsive threat or “fight or flight” stimulus; an undifferentiated emotion distress" [2] [1] https://www.jstor.org/stable/10.5406/amerjpsyc.131.1.0041 [2] https://insidethealcoholicbrain.com/2018/07/06/addiction-as-a-brain-disorder-of-emotion-regulation-part-4/ Edited September 22, 2018 by Alchemica 4 Share this post Link to post Share on other sites
LikeAshesWeFade Posted September 22, 2018 A couple of amazing posts again dude!! I look forward to having a read through them both this evening, love your work mate! 1 Share this post Link to post Share on other sites
Alchemica Posted September 23, 2018 (edited) Thanks @tarenna and @LikeAshesWeFade for the kind words Still going with the Trp. Finding it really quite useful. It's not so much a mood boost as what I need Modulating 5-HT more given me a view on 5-HT beyond it being a way of increasing personal "happiness". I'm not more "happy" - it's deeper than that. It's also deeper than 5-HT making octopi cuddly with empathogens, too. I like the model where "Serotonin influences social behaviour by shifting social preferences in the positive direction, enhancing the value people place on others’ outcomes." Trp augmentation may "influence the way they feel and think about themselves in a social context" and "serotonin function is related to positive social preferences, that is, the positive valuation of others’ outcomes" Serotonin's effects appear to depend on the social context: "serotonin amplifies neural representations of positive social preferences, whereas serotonin depletion shifts neural value computations toward selfish or even negative social preferences" "Serotonin is concentrated in discrete brain regions known to regulate social cognition and decision-making that have been collectively called “the social brain”. Depleting serotonin in normal individuals shifts their behaviour toward lack of impulse control and short-term gratification at the expense of long-term benefits. Enhancing brain levels of serotonin causes people to become more averse to harming others" Depleting brain serotonin levels in normal individuals results in a shift away from cooperative behavior in favor of short-term gain and results in antisocial behaviour, increased uncontrolled aggressive behavior, feelings of anger, quarrelsome behavior, and self-injury Low functioning "compromises the decision-making process by altering the ability to distinguish the magnitude of differences between immediate versus long-term rewards" and increases the tendency to choose the less probable outcome Low Trp manipulations result in the use of more self-references, more negative words, and fewer positive words Reduced serotonin function indeed impairs ones empathic abilities. Serotonin is important for promoting behavioural suppression or withdrawal in the face of aversive predictions Serotonin modulates human concerns for harm and fairness Serotonergic activities might strongly influence the sharing effect of emotions. It plays important roles in the regulation of individual behaviours that organize social group dynamics. Read How serotonin shapes moral judgment and behavior Vitamin D and 5-HT I'm a month into the L-methylfolate with the later added amino acids. It's reduced some symptoms quite nicely but it's pricey when I have house expenses. Trp will definitely remain as a useful amino acid for me but I'm keen for more affordable monoamine modulating vitamin options - maybe massive doses of L-methylfolate aren't needed and I can just use a mg/day or something. I also note how much the sun does for me... when I get out there properly "Vitamin D acts not only to induce serotonin synthesis, but also functions at an indirect, molecular-genomic stage to mimic SSRIs and MAO inhibitors" [1] "Fine-tuning serotonin concentrations in the synaptic cleft, vitamin D may be able to steer neurological control of such processes as social behaviour and depression." It is "hypothesized that an association between vitamin D insufficiency and low central serotonin concentrations represents a common denominator in a myriad of neuropsychiatric disorders." How does this apply to health? The core symptoms of ASD fluctuated in severity with changes in serum vitamin D levels in children: high-dose vitamin D3 regimens may ameliorate the core symptoms [2, 3] "...core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL." Vitamin D supplementation is associated with lower depressive and anxiety symptoms in psychotic illness [4] and addition of vitamin D to conventional antidepressive agents can improve antidepressive effect [5] I was always on the lower end dose when supplementing. A daily vitamin D intake of 1000–4000 IU (25–100 micrograms) should be enough to ensure optimal blood levels for most people [6] Anyone attest to benefits dosing higher? [1] https://www.ncbi.nlm.nih.gov/pubmed/30008960 [2] https://www.ncbi.nlm.nih.gov/pubmed/29629638 [3] https://www.ncbi.nlm.nih.gov/pubmed/27868194 [4] https://www.ncbi.nlm.nih.gov/pubmed/30245372 [5] https://www.ncbi.nlm.nih.gov/pubmed/29460820 [6] https://www.healthline.com/nutrition/how-much-vitamin-d-is-too-much Edited September 25, 2018 by Alchemica Share this post Link to post Share on other sites
Alchemica Posted October 2, 2018 (edited) Switching this around, how do we use the social to modulate monoamines? Is 5-HT something that is successfully modulated by the social? That's the other thing that causes a drastic reduction in symptoms for me - nourishing social interaction. The serotonergic system itself is highly responsive to social influences and social isolation has been shown to affect endogenous 5-HT release and 5-HT turnover and leads to a reduction in the excitability of DRN 5-HT neurons. Sure, initially the elevated serotonergic states where nice but eventually things seem to return to a homeostasis, likely as seen in clinical studies with Trp augmentation "During the first week of treatment, there was a significantly greater decrease in depression scores. No significant differences were noted at later time points." and if you're adding additional Trp, are you potentially providing extra fuel for an activated kynurenine pathway? Upping the monoamines helped but... I mean really, is fancy supplementation really alleviating issues at the source and improving life, or just a band-aid for real problems, like persistent social isolation? Part of me says, fix the aberrant underlying deficits and you'll start having better social approach and try more socialising whereas in reality, each "band-aid" is directing life force away from actively tackling the root causes. The bidirectional effects of the social on the biological could be more effective and stable than trying to up monoamines with anything. I've tried that approach before, a few times, but it's worth a retry. Riding through the nastiness of 'augmentation cost cutting', feeling quite extra crap, and more attempted action even though I feel crap. Often the only way that works... I'm at the point Trp isn't doing much more, other than inducing side-effects and becoming very blunting. More so than just switching favour between hedonic short-term rewards in favour of longer-term ones, actually feeling extremely anhedonic. It switched the impulsivity down, tackled negative emotional dysregulation well, for a bit. PRN stuff it feels. Do social factors induce cascading serotonergic abnormalities? It seems very difficult to climb back to any level of health if you condition social defeat and isolation. We too easily isolate and subordinate people with lower mental health, as they do to themselves, how much does that cascade into crippling mental illness? How much of a role does the serotonergic system play in that? Serotonin is probably most central in its relation to social status functioning [1] Changes in serotonergic function seems to directly affect perceived social status. "Social subordination leaves one fidgety, easily perturbed, and their behaviour seems to be largely controlled by external stimuli rather than being self-directed. [they are] prone to impulsive behavior including impulsive aggression." 5-HT appears - important in developing nourishing social contacts - contributes to the appraisal of the social emotional cues - increases the perception/interpretation of social stimuli - It stimulates pro-social behaviour, which leads to high levels of cooperation and improved perception of social cues In a simplistic framework: "Serotonin levels are not innate and inflexible. They are themselves the product of social status. The higher your self-esteem and social rank relative to those around you, the higher your serotonin level is. Experiments with monkeys reveals that it is the social behavior that comes first. Serotonin is richly present in dominant monkeys and much more dilute in the brains of subordinates. Cause or effect? Almost everybody assumed that the chemical was at least partly the cause: it just stands to reason that the dominant behavior results from the chemical, not vice versa. It turns out to be the reverse: serotonin levels respond to the monkey’s perception of its own position in the hierarchy, not vice versa." “Contrary to what most people think, high rank means lower aggressiveness, even in vervet monkeys. The high-ranking individuals are not especially large, fierce or violent. They are good at things like reconciliation and recruiting allies. They are notable for their calm demeanor. There is little doubt that the monkeys mood is set by its high serotonin levels. If you artificially reverse the pecking order so the monkey is now a subordinate, not only does its serotonin drop, but its behavior changes, too. Moreover, much the same seems to happen in human beings." - Genome The activity of 5-HT neurons is highly vulnerable to stress. Stress → social withdrawal/low mood → social isolation and continuous social subordination. Each of those declines is another hit to the functionality of the serotonergic system. It forms a negatively re-enforcing cascade. [1] https://www.ulm.edu/~palmer/TheBiochemistryofStatusandtheFunctionofMoodStates.htm "Serotonin dysregulation found in depression and other psychiatric disorders may go hand-in-hand with deficits in initiating social interaction, impaired learning from social interaction experience and making adverse decisions in social situations." Edited October 2, 2018 by Alchemica 2 Share this post Link to post Share on other sites
immanuel Posted November 23, 2018 (edited) Well I did a bit of reading into this and came across a few sources that could be considered dietary. A few purely natural sources here: https://www.longecity.org/forum/topic/73458-natural-5-ht1a-agonistsantagonists-pssdand-cognitive-function/ Berberine The anxiolytic mechanism of BER might be related to the increase in turnover rates of monoamines in the brain stem and decreased serotonergic system activity. Moreover, BER decreased serotonergic system activity via activation of somatodendritic 5-HT1A autoreceptors and inhibition of postsynaptic 5-HT1A and 5-HT2 receptors. https://www.ncbi.nlm.nih.gov/pubmed/15350820 Creatine These results indicate that the antidepressant-like effect of creatine is likely mediated by an interaction with 5-HT1A receptors. https://www.ncbi.nlm.nih.gov/pubmed/23352985 Ginger In this study, bioactivity-guided fractionation of a ginger extract identified nine compounds that interact with the human serotonin 5-HT(1A) receptor with significant to moderate binding affinities https://www.ncbi.nlm.nih.gov/pubmed/20363635 Sodium butyrate In conclusion, NaB may exert antidepressant-like effects in combination with EB in ovariectomized female rats through 5-HT1A receptor, via altering the expression of 5-HT1A in the hypothalamus. https://www.sciencedirect.com/science/article/pii/S016643280800497X Also Myo-inositol may act like SSRIs in the brain: Several studies have proposed a selective serotonin reuptake inhibitor-like role for myo-inositol, likely due to the fact that myo-inositol is the second messenger of serotonin https://www.ncbi.nlm.nih.gov/pubmed/22031267 Omega 3 fatty acids We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. https://www.ncbi.nlm.nih.gov/pubmed/?term=Vitamin+D+Vitamin+D+and+the+omega-3+fatty+acids+control+serotonin+synthesis+and+action%2C+part+2%3A+relevance+for+ADHD%2C+bipolar+disorder%2C+schizophrenia%2C+and+impulsive+behavior Exercise Several lines of research suggest that exercise increases brain serotonin function in the human brain. Post and colleagues56 measured biogenic amine metabolites in cerebrospinal fluid (CSF) of patients with depression before and after they increased their physical activity to simulate mania. Physical activity increased 5-HIAA, but it is not clear that this was due to increased serotonin turnover or to mixing of CSF from higher regions, which contain higher levels of 5-HIAA, with lumbar CSF (or to a combination of both mechanisms). Nonetheless, this finding stimulated many animal studies on the effects of exercise. For example, Chaouloff and colleagues57 showed that exercise increased tryptophan and 5-HIAA in rat ventricles. More recent studies using intracerebral dialysis have shown that exercise increases extracellular serotonin and 5-HIAA in various brain areas, including the hippocampus and cortex (for example, see58–60). Two different mechanisms may be involved in this effect. As reviewed by Jacobs and Fornal,61 motor activity increases the firing rates of serotonin neurons, and this results in increased release and synthesis of serotonin.62 In addition, there is an increase in the brain of the serotonin precursor tryptophan that persists after exercise. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077351/#!po=28.2609 Edited November 24, 2018 by manuel 1 Share this post Link to post Share on other sites
Alchemica Posted April 26, 2019 (edited) Trying different proteins for serotonergic effects (along with Mg/Zn etc) these days Protein source tryptophan from seeds with a high tryptophan-to-total protein ratio can be comparable to pharmaceutical grade tryptophan in some studies [1, 2] They are nutrient-dense and mostly anti-nutrient-free. The seeds of Cucurbita sp.have been traditionally used as medicine. Among the Cucurbitaceae members, pumpkin seeds are big, abundant, and edible. Yet, these seeds are mostly discarded as agro-industrial wastes [3]. They are rich in protein, polyunsaturated fatty acids (PUFA), minerals (magnesium, phosphorous, copper and potassium, iron, zinc, manganese), carotenoids, beta-carotene, and Vitamin E "...a remarkable assortment of health-enhancing nutrients, from magnesium, protein, niacin, and zinc, to its high concentration of tryptophan and essential fatty acids, pumpkin seeds provide a powerful health punch" - anti-inflammatory and anti-oxidative properties - protective activity against cardiovascular diseases - hypoglycaemic properties: Acute consumption of 65 g of pumpkin seed markedly reduced postprandial glycemia. Pumpkin seed has potential as a hypoglycemic food [4] - because of the high tryptophan content, pumpkin seeds might ease depression, anxiety, nervous irritability and insomnia - shown to improve the iron status I like other 'waste' products that are healing, too. [1] https://www.ncbi.nlm.nih.gov/pubmed/18066139 [2] https://www.ncbi.nlm.nih.gov/pubmed/16053244 [3] https://www.ncbi.nlm.nih.gov/pubmed/28463796 [4] https://www.ncbi.nlm.nih.gov/pubmed/30055778 Sure I try to put love into some meals but other times, just need sustenance. I chew through quite a bit of protein powder to keep at 0.8g/kg. Was doing well dropping weight by using that. I've tried so many proteins from hemp to soy but just settle on whey most of the time. Epidemiological and clinical studies have shown that dairy products have beneficial effects on cognitive decline and dementia, which may in part occur through whey peptides [1] As I've sort of subjectively noticed, chronic ingestion of diets differing in protein source elicits marked differences in the brain tryptophan concentrations and serotonin synthesis [2]. and tryptophan concentrations and serotonin synthesis in brain neurons are remarkably sensitive to which protein is present in a meal [3]. Whey protein has been proposed as a potential functional nutritional food supplement that prevents the progression of neurodegenerative disorders [4] and and useful for metabolic disorders [5,6] A hydrolyzed protein source may be more adequate to increase brain tryptophan and 5-HT function compared with intact alpha-lactalbumin protein or pure tryptophan [7]. While there have been "no significant changes in clinical outcomes" in some neurodegenerative disorders like Parkinson's in human studies, it improves some biomarkers [8] Whey consists of a heterogeneous group of proteins, including beta-lactoglobulin (35%), alpha-lactalbumin (12%), proteose peptone (12%), immunoglobulins (8%), and bovine serum albumin (5%) Due to greater solubility, more rapid digestion, and resultant higher plasma concentrations of amino acids, whey appears to be a favourable protein to provide nutritional and functional benefits. alpha-lactalbumin: - Lactalbumin increased plasma tryptophan (3-fold) and the tryptophan ratio (50%) [9] - may enhance sustained alertness early in the morning after an overnight sleep, most likely because of improved sleep [10]. - Dietary protein rich in alpha-lactalbumin improves cognitive performance in stress-vulnerable subjects via increased brain tryptophan and serotonin activities. - Supplements of lactalbumin may be useful for nutrition research in relation to age- or disease-related memory decline [11] [1] https://www.ncbi.nlm.nih.gov/pubmed/30011836 [2] https://www.ncbi.nlm.nih.gov/pubmed/23395255 [3] https://www.ncbi.nlm.nih.gov/pubmed/19454292 [4] https://www.ncbi.nlm.nih.gov/pubmed/29199432 [5] https://www.ncbi.nlm.nih.gov/pubmed/26516411 [6] https://www.ncbi.nlm.nih.gov/pubmed/25888881 [7] https://www.ncbi.nlm.nih.gov/pubmed/18648776 [8] https://www.ncbi.nlm.nih.gov/pubmed/27423583 [9] https://www.ncbi.nlm.nih.gov/pubmed/23395255 [10] https://www.ncbi.nlm.nih.gov/pubmed/15883425 [11] https://www.ncbi.nlm.nih.gov/pubmed/16174675 Edited April 26, 2019 by Alchemica Share this post Link to post Share on other sites
kindness Posted May 5, 2019 How are your testosterone levels? Assuming male here... 1 Share this post Link to post Share on other sites
Alchemica Posted May 5, 2019 (edited) Good point @Kindness. Probably quite messed up... Have been seeing what a *little* bit more carbs in the diet does, seems to be one part of the problem, potentially contributing to the shocking sleep quality and waking up 2am every morning... I went quite restrictive on carbs and a lot of people seem to find such messes with their sleep, potentially in part through the influence on 5-HT I've noted how socially modulated it is. The brain state caused by prolonged social isolation seems to involve neuropeptides Edited May 5, 2019 by Alchemica Share this post Link to post Share on other sites
kindness Posted May 5, 2019 Just wondering about that as a lot of those symptoms are similar to ones I endure and that’s due to low test count. Recently had a blood test to confirm 1 Share this post Link to post Share on other sites
