I am going to have to warn everyone not to combine 5-HTP with the C60 protocol as I did in my version of the protocol because of a negative reaction I had this April to 5-HTP and which took a few months to resolve.
The side effects are related to excess serotonin which downregulated (reduced) the number of my serotonin receptors and was fixed by upregulating (increasing) the number of serotonin receptors, as well as treating other side secondary effects caused by serotonin.
I further recommend not using other serotonin promoting and/or SSRI-like agents like SAM-e or St. Johns Wart (or any other neurotransmitters aside from serotonin) since they could have similar effects because of their serotonin enhancing properties. Since I only used 5-HTP a handful of times with the protocol, and never outside of it, this could indicate that taking the C60 protocol along with supplements or pharmaceuticals that alter any neurotransmitter balance or stimulate neurotransmitters could cause a more rapid than normal upregulation or downregulation of those receptors.
I am going to describe what I did to correct this problem and recommend anyone who did use 5-HTP with the C60 protocol to please use collagen, shilajit or fulvic acid (BUT preferably COLLAGEN) in the manner described in the following serotonin upregulation protocol I have written out below; UNLESS they show symptoms of serotonin syndrome which would require immediate medical treatment.
Please see if you have any of the symptoms of excess serotonin described by Jason Malek Russo I have posted further below.
Eventually I will also write a more detailed post on a new thread about this serotonin upregulation protocol because I discovered (quite unintentionally) while correcting this problem that upregulating serotonin receptors removes the suppressive effect serotonin exerts over dopamine activity. By removing serotonin's block on dopamine my creativity has increased in important ways such as the fact my sense of smell is enhanced, and I am more emotionally sensitive to music and art, including an improved sense of humor.
In general, I feel much more emotionally alive and creative than I have in quite a few years years.
Before I begin, I want to mention a few points.
One is that I likely had already downregulated my serotonin receptors years ago by using a large amount of serotonin-generating supplements such as SAM-e for liver health. Many common supplements, like curcumin, when taken in excess can increase serotonin levels and elevating serotonin activity tends to downregulate serotonin receptors.
Thus, I may have already been susceptible to a negative reaction to adding 5-HTP to the C60 protocol because my serotonin receptors had already been lowered/downregulated from previous years of supplementation.
I now believe I might have been experiencing a low-level of anhedonia years before I had started either the mito protocol or the C60 protocol, but adding 5-HTP to the protocol brought this issue to a head where it became much more noticeable. For example I had noticed a steady drop off in creativity and a dulling of my sense of humor years ago, that has now been corrected by the serotonin reducing protocol I created out of necessity.
However, 5-HTP is arguably a more a potent serotonin stimulant than SAM-e or pharmaceutical SSRIs like Paxil because SSRIs usually do not increase the total number of serotonin neurotransmitters in the body (like 5-HTP does). Instead, SSRIs keep the same total number of serotonin neurotransmitters the same while keeping them longer in the synapse.
I might also have been susceptible to 5-HTP because my GABA receptors, which inhibit excess serotonin activity, might have been downregulated because of past use of alcohol (moderately) and using nicotine at the same time as drinking (from vaping and Swedish snus, not traditional combustible tobacco which I have not used except a few times in school) which both overstimulate/decrease GABA receptors by overstimulating them with higher GABA.
For reference purposes I made extensive use of Jason Malek Russo's work on excess serotonin and its numerous negative side effects from both SSRIs and naturally occurring SSRIs like SAM-e and 5-HTP.
Russo (who used to post here and at other forums as Area-1255) was an invaluable source of information because, as far as I could tell, he is 100% correct in his descriptions of how serotonin and its receptors operate.
HOWEVER I should warn the reader that for treatment of various ailments his advice was NOT ALWAYS wise or safe. For example, he recommends phenibut on his blog for certain ailments, but phenibut has dangerous side effects. I would STRONGLY recommend someone looking at his works in an attempt to understand an ailment (for any issue, not just ones that are serotonin related) to NOT automatically take a drug or supplement he recommends unless they do careful research on its side effects, check if there are safer alternatives that have similar or better effects, and, preferably, ask people here if his treatment suggestion is a good idea.
Background - In general, neurotransmitters and neurotransmitter receptors act like baseballs (neurotransmitters) and catcher's mitts (neurotransmitter receptors) where the receptors "catch" the neurotransmitter. Hence, serotonin receptors "catch" serotonin transmitters, dopamine receptors "catch" dopamine neurotransmitters, etc, etc.
Although this is a gross oversimplification of a complex topic, it does capture the basic idea of how neurotransmitters relate to their receptors. As a general rule (which has exceptions) receptors decrease (decrease = downregulate) in number when there are too many neurotransmitters agonizing/activating them.
When receptors, such as serotonin receptors, decrease/downregulate in number they become overly sensitive to normal changes in serotonin neurotransmitter levels because there are too many serotonin neurotransmitters chasing too few serotonin receptors to "catch" them.
The overstimulation of ANY receptor with any neurotransmitter can become dangerous.
Therefore, in general, the way to improve downregulated neurotransmitter imbalances is to increase (increase = upregulate) the number of receptors so the remaining receptors do not become "overwhelmed" and the rest of the neurotransmitter system is rebalanced.
Fortunately, receptors can be upregulated provided there is not significant damage to the underlying neurons.
Upregulation is usually accomplished by gradually decreasing receptor exposure to the neurotransmitters, either by reducing the amount of neurotransmitters (such as by cutting serotonin levels) or by blocking the receptor from interacting with the neurotransmitter, such as by upregulating beta adrenoreceptors with beta blockers like propranolol which limits the beta adrenoreceptor's contact with adrenaline/epinephrine and noreadrenaline/norepinephrine.
The main problem I encountered in April about an hour after trying the C60 protocol with 5-HTP was from downregulated serotonin receptors.
The symptoms forced me to go the ER because of worry that I was suffering from serotonin syndrome, which requires immediate medical care.
The symptoms of excess serotonin (which were corrected individually in a phased approach over a period of months) included loss of appetite, nervousness to sounds and certain shapes and lighting, anxiety attacks from excess adrenaline release (usually occurring after eating meat), elevated blood pressure from my normal 108/78 which consistently became 125-135 / 82-94, and high anxiety sensitivity to citric acid and methylation because of its activation of the PNMT pathway which generates adrenaline and noreadrenaline.
This serotonin downregulation created secondary effects caused by downregulated beta receptors from excess adrenaline release, dysregulated GABA function, intestinal upset from downregulation of serotonin receptors in the GI tract, difficulty processing fat and protein, intolerance of certain supplements because the P450 chromosome in my liver appeared to be downregulated.
This P450 chromosome is necessary for processing medicines (hence why SSRI's are dangerous to take with grapefruit juice because grapefruit juice also downregulates P450 -
Insights into PSSD - A Collection of Data & Detailed Analysis of the Etiology and Pathology of Post-SSRI-Sexual Dysfunction as well as Possible Novel Treatment Approaches
One of the most distinguishable traits of all SSRI's, with the exception only of those with a short half life (and these are used for other purposes) ~ is that each SSRI not only generally has a very long half-life, but also that each drug tends to have prominent effects on liver enzymes; generally CYP3A4 and CYP2C19 or cytochrome P450. The implications of this binding are many, one of the main problems here is that by these drugs binding to liver enzymes, depending on which one ~ there is a possibility of changing the breakdown of other drugs, or delaying their elimination - this can lead to amplified side-effects of other drugs and thus further causes physiological disturbances especially if the other drugs have even so much of a parallel in regards to their mechanism of action […]
Now another big no-no, in fact one that is warned about ON-LABEL, is combining these anti-depressant drugs with NATURAL inhibitors of these enzymes, related cytochrome enzymes, or downstream , fairly related enzymes - one of the most discussed is GRAPEFRUIT JUICE.
By combining grapefruit juice you may increase the risk of overdosing on multiple drugs, and if you then take a second inhibitor, like LUVOX; the effects are then ADDITIVE....which essentially means that combining one simple 6oz glass of grapefruit juice with luvox, and then a blood pressure pill - could very easily KILL you or land you in the hospital with nearly uncontrollable bouts of panic, or immobilization stress and severe HYPOTENSION...if you do survive such a combination, the almost total loss of oxygen delivery during the periods of treatment and recovery may result in permanent nerve and blood vessel damage!
Other causes aside from receptor dysregulation were ruled out with medical test results that showed normal vital signs.
Blood work, liver and kidney enzymes were normal.
A complete abdominal ultrasound came back normal.
A brain MRI with contrast showed normal brain function.
X-rays and EKGs of the heart and circulatory system came back normal and showed no signs of heart or circulatory disease.
The phased approach to correct these problems is outlined below.
During all of the steps I used weight lifting to increase testosterone to counteract serotonin and ate at least 12 eggs each week to provide the liver with choline because egg yolks (if served sunny side up, and are not scrambled) contain the type of choline (phosphatidylcholine) the liver prefers.
I strongly recommend not to combine supplements from the different steps of this protocol at the same time because their combination might be too strong for an imbalanced system. For example, no one should combine Omega 3 fish oil and propranolol (both of which I used) at the same time because both of them lower blood pressure and heart rate and taking them at the same time could cause a dangerous decrease in heart rate and/or blood pressure.
Symptoms of excess serotonin -
Signs of Too Much Serotonin
SENSORY EFFECTS
Over-Sensitivity to sounds, especially loud noises. Excessive jumpiness or even anxiety in response to sudden sounds or movements(1) (2).
Visual distortions, height / depth alteration, hallucinations(3) (4).
Words may appear out of place, or your perception of what you are reading may be entirely different. { e.g reading the third line thinking its the second} (5)
Sensitivity changes to light, sedation or no response to darkness(6) (7) (8) (9).
Lack of pain sensation, or HYPO Algesia, some individuals with high serotonin display such a lack in pain perception/sensitivity that it mirrors the effects of those under the influence of PCP. Pain asymbolia can be misdiagnosed as high serotonin(10) (11).
Tinnitus, ringing in ears(12)(13).
Vertigo. Dizziness. Room spinning(14) (15).
BEHAVIORAL / MENTAL EFFECTS
Delirium. Usually including abnormal forms of panic or worry along with various disperceptions(16) (17).
Depersonalization. Feeling out of place, out of body, or that events or surroundings are surreal(18)(19).
Frequent or occasional episodes of psychosis, paranoia, pathology changes, and obsessional behavior(20)(21).
Religious delusions and religious over-engagement. (some cult leaders are hypothesized to have elevated, but not toxic levels of serotonin)(22). The best book on this is "Biology of Religious Behavior : The Evolutionary Origins of Faith and Religion".
Unexplained agitation or inner restlessness(23).
Dystonia, tic-like behaviors, punding; repetitive behaviors(24) (25) (26)(27).
Frequent crying episodes in children, unwarranted panic or extreme anxiety(28).
Low/Absent Libido(29)
Emotional Anhedonia / Apathy / Blunt AFFECT (30) (31) (32) (33) (34)
Jittery, nervous hands, tremors, impatient(35) (36) (37).
Depression , despair, lack of motivation(38) (39).
Reading/Comprehension deficits(40).
PERIPHERAL / INTERNAL EFFECTS
Persistent nausea, unexplained/stress induced; not due to motion sickness which is more acetylcholine based. (41) (42)
Diarrhea/IBS Symptomology(43) (44) (45).
Part 1 - Upregulation of serotonin receptors by taking shilajit for 1 month using Double Wood's brand of shilajit (500 mgs shilajit per capsule standarized to 20% fulvic acid).
Shilajit was used to upregulate my serotonin receptors because its active ingredient, fulvic acid, reduces serotonin. Although I am not sure how this mechanism works I suspect it occurs by converting serotonin into melatonin because I felt sleepy after taking it and the conversion of serotonin into melatonin is one of the main ways the body gets rid of excess serotonin.
I took 1 capsule of shilajit for one week then increased to 2 capsules for the second week, then 4 capsules for the week after, and then tapered off the last week to just 1 capsule.
This process was completed in one month.
It was important to GRADUALLY increase the dose because trying to take too much too fast would be excessive for an imbalanced system, although I did have SSRI withdrawal symptoms the first week. The SSRI withdrawal symptoms included feeling depressed if I was in a dark room and not outside in sunlight. The withdrawal symptoms subsided after the first week.
Beginning with a low, gradual, dose allowed tolerance to the lower serotonin levels to build up in an orderly fashion.
It was crucial to ALWAYS take shilajit with a meal that included meat because the tryptophan in meat kept serotonin levels from dropping too low.
I could also have used fulvic acid or collagen to reduce serotonin.
If using fulvic acid keep in mind it cannot be applied in pure form to the mouth because it is acidic. Instead a few drops (3 to 5) need to be diluted in water and drunk.
There is a concern that diluting fulvic acid in tap water (or taking shilajit capsules with tap water) could cause the fulvic acid to react with chlorine to create a toxic substance.
However, chlorinated water has only trace amounts of chlorine so I took shilajit with only a small sip of tap water.
Because shilajit contains minerals taken from the Himalayas I used EDTA after I stopped using shilajit to chelate any heavy metals that might not have been removed from the processing of shilajit, although I suspect heavy metals were largely removed in the processing operations because shilajit is not naturally standardized to 20% fulvic acid.
Hydrolized collagen can also be used to lower serotonin.
I STRONGLY RECOMMEND using collagen as follows for most people who want to lower somewhat elevated serotonin levels because collagen is better studied than shilajit.
I recommend collagen for anyone who took 5-HTP with the protocol, even if they have no symptoms of excess serotonin, as a precaution.
I also recommend collagen for anyone with signs of mild serotonin excess and who has not used 5-HTP because serotonin has a number of negative side effects even at slightly elevated levels.
Ideally, serotonin levels should be slightly below average to moderately below average, although not reduced to an extreme level.
Collagen should be taken on an empty stomach in the morning 1 to 2 hours before a meal with meat to lower serotonin. If collagen is taken with a meal it will not reduce collagen.
It is important to take a meal with meat 1 to 2 hours later so meat provides enough tryptophan to prevent collagen from dropping serotonin levels too low.
Remember that your system will adjust best with a gradual lowering of serotonin.
This is not recommended for those who need higher levels of serotonin.
For those with no obvious signs of excess serotonin this protocol should be used only occasionally to improve mood and creativity, and not excessively.
If you are unsure if your serotonin levels are high I recommend going to a Labcorp and asking for a urine test for serotonin's metabolite, 5-H1AA, to check.
I recommend doing this even if you have to pay out of pocket and setup a urine test appointment yourself because doctor's might be reluctant to run a test that would implicate a major cashcow for the pharmaceuticals, namely SSRIs, which have been shown to be no better than placebos 50% of the time at reducing depression, and which have a number of negative side effects.
Serotonin Antagonists
Shilajit is found to protect against serotonin induced cognitive deficits by rapidly depleting serotonin activity; especially in the Hippocampus. This is also a proposed mechanism by which Shilajit rejuvenates normal libido / sexual function.
Pharmacokinetics of acute tryptophan depletion using a gelatin-based protein in male and female Wistar rats
The essential amino acid tryptophan is the precursor of the neurotransmitter serotonin. By depleting the body of tryptophan, brain tryptophan and serotonin levels are temporarily reduced. In this paper, several experiments are described in which dose and treatment effects of acute tryptophan depletion (ATD) using a gelatin-based protein-carbohydrate mixture were studied in male and female Wistar rats. Two or three doses of tryptophan depleting mixture resulted in 65-70% depletion after 2-4 h in males. ATD effects were similar in females, although females may return to baseline levels faster. Treatment effects after four consecutive days of ATD were similar to the effects of 1 day of treatment. Object recognition memory was impaired 2, 4, and 6 h after the first of two doses of ATD, suggesting that the central effects occurred rapidly and continued at least 6 h, in spite of decreasing treatment effects on plasma tryptophan levels at that time point. The method of acute tryptophan depletion described here can be used to study the relationship between serotonin and behaviour in both male and female rats.
Part 2 - Reduce blood pressure with Omega 3 from eating salmon (Note it might have been better if I done Part 3 before Part 2. See Part 3 below for more information).
After finishing with shilajit I ate 6 ounces of salmon, once a week, for two weeks to lower blood pressure because Omega 3 reduces aldosterone which is the main hormone that regulates sodium retention in the kidneys.
Before April of this year my blood pressure was normally 108/78 at rest.
But 5-HTP raised it to around 125 to 135 / 82 to 92.
SSRIs (both pharmaceutical and "natural" like 5-HTP or St. Johns Wart) have been implicated in the creation of cardiovascular disease because their downregulation of serotonin receptors causes disruption of cardiovascular function and releases of adrenaline that downregulate beta receptors.
Omega 3 was surprisingly effective after eating salmon once a week for two weeks.
By the second week my resting blood pressure dropped to 105-112 / 70-75, which was better than it was before this started in April.
Omega 3 also completely eliminated intestinal bloating and abdominal cramping, for some reason.
I also hoped that Omega 3 would reduce anxiety attacks caused by serotonin raising adrenaline levels but I found that Omega 3, for some reason, increased anxiety (perhaps I should have done part 3 before part 2).
Long-term antidepressant use may double the risk of heart disease
Using data from UK Biobank, a large-scale biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants, the team linked comprehensive health data with prescription and disease data (using GP records) on 222,121 adults aged between 40 to 69-years old.
They compared the risk of developing adverse health outcomes between those who had not taken antidepressants and those who had been treated with the most commonly prescribed antidepressants in England over ten years. These were categorised by drug class as selective serotonin reuptake inhibitors often known as SSRIs, called citalopram, sertraline, fluoxetine and paroxetine and ‘other’ non-SSRI antidepressants called mirtazapine, venlafaxine, duloxetine and trazodone.
The researchers found that, once pre-existing risk factors had been taken into account, long-term antidepressant use was associated with an increased risk of coronary heart disease, and an increased risk of death from cardiovascular disease and from any cause. The risks were greater for non-SSRI antidepressants (mirtazapine, venlafaxine, duloxetine, trazodone), with the use of such drugs associated with a two-fold increased risk of coronary heart disease, cardiovascular mortality, and all-cause mortality at ten years.
Can Serotonin Cause High Blood Pressure / Hypertension ? (Serotonin causing High Blood Pressure)
Serotonin is implicated in a number of cross-reactions in the nervous system, and there are serotonin receptors located directly in/on the heart/atrium. Increased activity of the serotonin receptors 5-HT2B and 5-HT4 is shown on failing hearts. (3) (4)
As such , chemicals/drugs that block these two serotonin receptors are being investigated/trialed for the treatment of those with various forms of heart disease. (5) (6)
Namely, right ventrical heart failure (5-HT2B) and congestive heart failure (CHF) along with tachycardia (5-HT4).
In addition to central heart failure, serotonin itself is dangerous in moderately-elevated to substantially elevated amounts, high plasma serotonin levels are found to cause primary pulmonary hypertension (7) (8) (9).
Additionally, serotonin is found to , along with adrenaline, mediate stress-induced increases in systolic blood pressure, which essentially means that serotonin is about half of the reason why blood pressure can go up in response to stress(10) (11). Part of this has to do with the serotonin induced accumulation of ALDOSTERONE via 5-HT4 receptor activation(12).
This means that serotonin allows for sodium retention as well as excessive calcium ion influx via that receptor.
Finally, anabolic steroid use, especially that of nandrolone or progestin based steroids - leads to the (abnormal) downregulation of serotonin autoreceptors which then may lead to the direct enhancement of serotonin signaling at the 5-HT4 receptors - which may be a valid hypothesis or at the least, a contribution by AAS in heart failure/enlargement(13) (14) (15).
Omega-3 fatty acids and blood pressure
Omega-3 appear to suppress aldosterone secretion compared to physiological stimulus such as angiotensin II, ACTH or K+. This effect may be related to changes in intracellular signal transduction, alterations in plasma viscosity or to a lower activity of angiotensin converting enzyme (ACE). ACE is the enzyme that transform angiotensin-I into angiotensin-II, that controls blood pressure and regulates body fluid volume by modulating renin-angiotensin-aldosterone system. The inhibition of this enzyme leads to reduce angiotensin-II production, producing vascular relaxation and reducing aldosterone secretion(Reference Fischer, Dechend, Qadri, Markovic, Feldt, Herse, Park, Gapelyuk, Schwarz, Zacharzowsky, Plehm, Safak, Heuser, Schirdewan, Luft, Schunck and Muller9). Besides, ω-3 PUFA have been linked to increase production of endothelial nitric oxide (eNO) in animal models, and on the other hand, the L-arginine-NO system increase PUFA metabolism(Reference Das10). In addition, EPA and DHA can inhibit proteinuria development, suppress hypertension in stroke-prone spontaneously hypertensive rats and prevent excessive growth of smooth muscle by inhibiting the transforming growth factor beta (TGF-β) synthesis(Reference Das10). Also, it has been reported that DHA promotes vascular smooth muscle apoptosis, perhaps because of a modulatory effect on the renin-angiotensin-aldosterone system. Thus, it has been suggested that through these two mechanisms, DHA help to prevent vascular wall fibrosis and secondary hypertension development
Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research
Part 3 - Upregulate beta receptors with the beta blocker propranolol to halt anxiety attacks and upregulate beta receptors.
Because of periodic anxiety attacks and because serotonin's overactivation of adrenaline probably downregulated my beta adrenoreceptors/adrenergic receptors I had my doctor prescribe propranol to block adrenaline's action and upregulate the beta receptors.
I used 10-20 mgs of propranol a day for a month. Then I tapered off propranolol by taking 10 mgs every other day for two weeks and then 10 mgs once a week for two weeks.
It is important to taper off beta blockers gradually because the heart can become dependent on them to a point where suddenly withdrawing from them could cause a heart attack, or other heart problems.
While on propranolol I went to places where I had anxiety attacks to "unlearn" the fear response.
This proved effective because I could go anywhere I wanted as needed so long as I was on propranol.
I also noticed that eating meat and protein became normal again, apparently because increased adrenaline and adrenaline rush "flight or fight" responses interfere with the GI tracts ability to absorb food.
Therefore, propranolol's blockade of beta receptors prevented adrenaline from interfering with eating.
Part 4 - Upregulate GABA and upregulate P450 in the liver using Culturelle Probiotic.
To further eliminate anxiety symptoms, for a month I took with meals two pills of Culturelle's Probiotic of lactobacillus rhamnosus to upregulate GABA receptors with Swanson's Prebiotic of FoS to feed the L. rhamnosus bacteria.
GABA receptors are responsible for suppressing both serotonin and adrenaline release and L. rhamnosus has been shown to upregulate GABA in rats.
L. rhamnosus also enhances serotonin transport systems (SERT) in the intestines (over 90% of serotonin is located in the GI tract). By activating SERT L. rhamnosus should reduce excessive interactions of serotonin with serotonin receptors, at least in the gut where most of serotonin is stored.
In order to further improve my digestive system I also took Culturelle to upregulate the P450 liver enzyme (and its related enzymes like CYP3) which is responsible for the liver processing medicines and other foods.
P450 was probably downregulated because of serotonin.
Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve
GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.
Effect of Lactobacillus rhamnosus GG supernatant on serotonin transporter expression in rats with post-infectious irritable bowel syndrome
The levels of SERT mRNA and protein in intestinal tissue were higher in rats treated with LGG-s than in control rats and PI-IBS rats gavaged with PBS during the whole study. Undiluted LGG-s up-regulated SERT mRNA level by 2.67 times compared with the control group by week 2, and SERT mRNA expression kept increasing later. Double-diluted LGG-s was similar to undiluted-LGG-s, resulting in high levels of SERT mRNA. Triple-diluted LGG-s up-regulated SERT mRNA expression level by 6.9-times compared with the control group, but SERT mRNA expression decreased rapidly at the end of the second week. At the first week, SERT protein levels were basically comparable in rats treated with undiluted LGG-s, double-diluted LGG-s, and triple-diluted LGG-s, which were higher than those in the control group and PBS-treated PI-IBS group. SERT protein levels in the intestine were also comparable in rats treated with undiluted LGG-s, double-diluted LGG-s, and triple-diluted LGG-s by the second and third weeks. SERT mRNA and protein levels in the brain had no statistical difference in the groups during the experiment.
CONCLUSION
LGG-s can up-regulate SERT mRNA and protein levels in intestinal tissue but has no influence in brain tissue in rats with PI-IBS.
Lactobacillus rhamnosus induces CYP3A and changes the pharmacokinetics of verapamil in rats
This report investigated the potential of gut microbiota-drug interactions between lactobacillus rhamnosus and verapamil via using wild type (WT) and Cyp3a1/2 knockout (KO) rats. In WT rats, administration of Lactobacillus rhamnosus for 14 days decreased systemic exposure of verapamil and increased its metabolite norverapamil in vivo, and resulted in gut microbiota-drug interactions. In Cyp3a1/2 KO rats, however, this interaction disappeared. Further studies found that Lactobacillus rhamnosus induced CYP3A activity and expression, and changed the composition of gut microbiota, thus changing the pharmacokinetics of verapamil. These results demonstrated the interaction between lactobacillus rhamnosus and verapamil, and indicated that the effect of gut microbiota on metabolic enzymes cannot be ignored.
Probiotic Administration Attenuates Myocardial Hypertrophy and Heart Failure After Myocardial Infarction in the Rat
Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial
Therapeutic Anti-Depressant Potential of Microbial GABA Produced by Lactobacillus rhamnosus Strains for GABAergic Signaling Restoration and Inhibition of Addiction-Induced HPA Axis Hyperactivity
Dietary supplementation with Lactobacillus rhamnosus JB-1 restores brain neurochemical balance and mitigates the progression of mood disorder in a rat model of chronic unpredictable mild stress
Part 5 - Improving MAO function with the mitochondrial protocol (Still ongoing).
To further ensure anxiety attacks do not return I am still using my version of the mito protocol once a week to restore MAO function.
Like GABA, MAO has a central role in eliminating excess adrenaline.
Since MAO is embedded within mitochondria, restoring mito function has a direct role in correcting anxiety disorders that are related to MAO dysfunction.
Once a week I take 1 gram of nicotinamide and 20 mgs PQQ on fission days and 2 grams of dihydromyricetin and 20 mgs PQQ on fusion days.
Then the following week I use 750 mgs NMN and 20 mgs PQQ for fission days because NMN reaches muscle and blood vessel tissue effectively.
I will start adding 100 mgs fisetin and 500 mgs quercetin once every two weeks to clear out any senescent cells.
I am doing 1 cycle a week.
I am not using AKG right now for either fission or fusion days in case my system is sensitive to glutamate which AKG increases (although I do not believe I was suffering from glutamate toxicity because, if I was, propranolol wouldn't have been effective at preventing anxiety attacks).
An energetic view of stress: Focus on mitochondria
Another important class of hormones released in response to certain stressors are catecholamines, particularly norepinephrine (NE) and epinephrine (E). Both are derived from the neurotransmitter dopamine, itself generated from the amino acid tyrosine. Interestingly, the biosynthetic enzymes involved in catecholamine degradation, the monoamine oxidases MAO-A and MAO-B are anchored to the outer mitochondrial membrane (Binda et al., 2011). Some reports also suggest that TH may be tethered to the mitochondrial surface (Wang et al., 2009; Baumann et al., 2016), although this may be tissue specific and inducible under certain conditions; more work is needed to examine this potential functional association of mitochondria with catecholamine synthesis and degradation.
Although much of the evidence so far is preliminary, it points to a substantial connection. Mitochondria seem to be central to the very existence of a stress response, serving both as mediators of it and targets for the damage it can do. To some of the researchers involved in this work, the stress response even looks like a kind of coordinated action by mitochondria throughout the body that interacts with the neurological processing.
“I think mitochondria are underrated,” said Martin Picard of Columbia University’s Irving Medical Center in New York, whose laboratory has helped to pioneer this research. “They’re the chief executive organelle of the cell.” Now scientists can explore what the implications of the organelles’ importance might be for future therapies.
Part 6 - Returning to the C60 Protocol (To be done following the mito protocol).
I will eventually use my version of the C60 protocol again (without 5-HTP!) to fix any additional damage that may have been caused by excess serotonin but which was not cleaned up by the previous steps.
I especially want to use it repair any stress my blood vessels and arteries may have suffered during this time. Although tests by my doctor showed no heart or circulatory issues it is possible that some of the stress could be a problem if left untreated by the C60 protocol decades in the future, and which is something current technology could not detect this early on.
Part 7 - Maintenance longterm.
I will use natural beta blockers like 70% dark chocolate and magnesium periodically to prevent beta receptors from downregulating again. I will also use Culturelle periodically to prevent GABA receptors from downregulating.
For anyone suffering from anxiety attacks caused by adrenaline surges it is probably better to consult with a doctor about getting a prescription for propranolol because its beta blocking effects upregulate beta receptors more rapidly across the entire body than natural beta blockers like dark chocolate and magnesium. A dose of 10 to 20 mgs propranolol a day for a month, followed by a gradual tapering off, should be enough to help most people.
Dark Chocolate Intake Buffers Stress Reactivity in Humans
To test whether dark chocolate consumption induced changes in stress hormone reactivity to acute psychosocial stress, we calculated general linear models with repeated measures while controlling for the pre-chocolate baseline of the respective stress hormone as covariate. Across all subjects, the TSST induced significant increases in cortisol, ACTH, epinephrine, and norepinephrine (all, p <0.001). The dark chocolate group showed a significantly blunted cortisol (interaction group-by-stress F(2.5/154.8) = 7.47, p <0.001, eta2 = 0.108, f = 0.35) (Fig. 1A) and epinephrine (interaction group-by-stress F(1.7/101.0) = 4.34, p = 0.021, eta2 = 0.066, f = .27) (Fig. 1B) reactivity to psychosocial stress compared to the placebo group. Additional controlling for age, BMI, and MAP did not significantly change these results (interaction group-by-stress cortisol: F(2.6/155.6) = 6.59, p = 0.001, eta2 = 0.100, f = 0.33; epinephrine: F(1.8/101.8) = 4.06, p = 0.025, eta2 = 0.065, f = 0.26). There were no group differences in terms of ACTH or norepinephrine stress reactivity (all, p > 0.26).
Edited by Kelvin, 09 October 2023 - 10:55 PM.
