tag:blogger.com,1999:blog-655962722302095847.post3464553590988881524..comments2024-03-27T20:20:54.505+01:00Comments on Epiphany: Regulation of the Arachidonic Acid (AA) Cascade to treat Inflammatory Disease via aspirin, diet, lithium or better still calcium channelsPeter Lloyd-Thomashttp://www.blogger.com/profile/10173383229834614994noreply@blogger.comBlogger33125tag:blogger.com,1999:blog-655962722302095847.post-82436556992705643762022-12-13T15:56:34.638+01:002022-12-13T15:56:34.638+01:00I see no mention that verapamil can cause hyperpro...I see no mention that verapamil can cause hyperprolactinemia...dragon-67https://www.blogger.com/profile/05996281035116298199noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-9104057568552274782020-05-30T10:53:52.766+02:002020-05-30T10:53:52.766+02:00Adam, it is not really known for sure why Verapami...Adam, it is not really known for sure why Verapamil helps some people with IBS-D. It did not help enough people to become an approved therapy.<br /><br />"The efficacy of the calcium channel blocker verapamil was prospectively studied in a group of 129 nonconstipated IBS patients meeting Rome II criteria [Quigley et al. 2007]. In this doubleblind study, 12-week study, patients were randomized to receive either placebo or the r-enantiomer of verapamil. Doses were adjusted at 4-week intervals, increasing from 20 mg p.o. t.i.d. to 80 mg p.o. t.i.d. as tolerated. The authors reported that the medication was generally well tolerated, without any significant adverse events being reported. Intention-to-treat analysis showed a significant improvement for the r-verapamil group for both primary efficacy variables compared with control, including global symptom scores (p¼0.0057) and abdominal pain/discomfort (p ¼ 0.05). Although not discussed in this preliminary report, verapamil may improve symptoms by modulating smooth muscle function in the gastrointestinal tract. Further studies are forthcoming from this active research group."<br /><br />Good luck!Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-33322763868016012442020-05-30T03:08:19.683+02:002020-05-30T03:08:19.683+02:00Sorry, I commented on the wrong thread! I'm go...Sorry, I commented on the wrong thread! I'm going to trial Verapamil before TSO as it's far cheaper. Probably combine with LDN, pregnenolone and some antioxidants. I have IBS-D so will be interesting to see how Verapamil affects that. If Verapamil affects the mucosal layer, would this affect intestinal permeability and therefore immune activation via this mechanism, say in the small intestine? Or are the effects just concentrated in the colon? I know the helminths also increase mucus production, so a similar effect there too.Adamhttps://www.blogger.com/profile/13685366728650876234noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-48459496171420708582019-05-29T09:58:04.380+02:002019-05-29T09:58:04.380+02:00Prada, that is interesting. The positive result wa...Prada, that is interesting. The positive result was achieved with a commercial Japanese product containing 40 mg/capsule of DHA, 40 mg/capsule of ARA, and 0.16 mg/capsule of astaxanthin.<br /><br />We should note that astaxanthin also has effects on the brain. <br /><br />Based on the old post above, I wonder what happens if you add a tiny dose of aspirin.<br /><br />So many people with autism take fish oil you would think some clever University researchers would put all the information together once and for all, so people stop using the "wrong" products. Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-32179553883634288762019-05-29T04:56:35.416+02:002019-05-29T04:56:35.416+02:00I found this article about Arachidonic Acid AA and...I found this article about Arachidonic Acid AA and autism. <br />https://www.omicsonline.org/efficacy-of-adding-large-doses-of-arachidonic-acid-to-docosahexaenoic-acid-against-restricted-2155-6105.S4-006.php?aid=3211<br />Coincidentally the only fish oil which has an effect on my daughter it is one with AA, EPA, DHA and Gamma-Linolenic Acid.pradanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-82611838312028442282017-10-04T14:45:55.558+02:002017-10-04T14:45:55.558+02:00Rape seed oil has an even better omega3:6 ration t...Rape seed oil has an even better omega3:6 ration than olive oil. It doesn't taste as good on a salad, but works great for cooking.<br />/LingAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-32941971839778526842017-08-12T23:07:22.732+02:002017-08-12T23:07:22.732+02:00I found some facts about a condition named AERD (A...I found some facts about a condition named AERD (Aspirin Exacerbated Respiratory Disease) that are very interesting both in respect to this blogpost and to the bigger picture of the hyperreactive immune system that is so common in autism.<br />Aspirin and also many other NSAIDs can cause AERD, and I just think that there might be an elevated risk for those with autism.<br /><br />"People with AERD often have high levels of cells called eosinophils in their blood and in their sinuses, which may lead to chronic inflammation of the airways. It has also been found that people with AERD have an impaired cyclooxygenase enzyme (COX) pathway, and produce high levels of leukotrienes. Leukotriene levels are further increased after ingestion of aspirin or NSAIDS, which is why patients develop reactions to these medications, and why anti-leukotriene medications are sometimes helpful as treatments.<br />(..)<br />Medications that block the production of leukotrienes (zileuton / Zyflo CR) or block the actions of leukotrienes (montelukast / Singulair and zafirlukast / Accolate) have been found to provide some benefit in treating the symptoms of AERD" <br />(https://aerd.partners.org/about-aerd/)<br /><br />"The disorder is thought to be caused by an anomaly in the arachidonic acid metabolizing cascade which leads to increased production of pro-inflammatory cysteinyl leukotrienes, a series of chemicals involved in the body's inflammatory response. (..) The underlying cause of the disorder is not fully understood, but there have been several important findings (see Wikipedia for full textblock)<br />(..)<br />There may be a relationship between aspirin-induced asthma and TBX21, PTGER2, and LTC4S."<br /><br />Are these genes involved in autism?<br /><br />/LingAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-80011223340976484082016-10-30T11:18:09.498+01:002016-10-30T11:18:09.498+01:00I am not sure what a megadose would be, but I trie...I am not sure what a megadose would be, but I tried somewhere between 3-5gms per day, quite a while ago, for apraxia. I did not worry about blood thinning since my daughter's fibrinogen tends to run high. It did nothing. RGhttps://www.blogger.com/profile/07458829468580940361noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-63765284994454664832016-10-30T01:50:56.626+02:002016-10-30T01:50:56.626+02:00Relevant to this discussion, some new research on ...Relevant to this discussion, some new research on Omega 3 fatty acids helping clear amyloid deposits from the brain. In at least one post-mortem study on donated brains from deceased individuals with ASD, it was found that there were highly elevated levels of amyloid-beta deposits in the brain.<br /><br />Here is the paper:<br /><br />http://www.fasebj.org/content/early/2016/10/07/fj.201600896<br /><br />It is thought that omega 6 and omega 3 fatty acids compete for the same enzymes so that if your diet has an abundance of one fatty acid over the other, the other fatty acid would be starved of enzymes necessary for proper metabolism. It is very, very, very hard to get too many Omega 3's relative to Omega 6's in diet, and the western diet has what many consider to be a very skewed ratio in favor of Omega 6's (all covered in Peter's post above).<br /><br />This discussion gets me to wondering if anyone has tried "megadosing" Omega 3's with respect to autism (I would imagine there might be Alzheimer's studies on the matter but I have not looked yet). The only known risk factor I know about Omega 3's is that they do thin the blood which can be a pretty big risk factor, though I do not know if there is a ceiling as to how much megadose Omega 3 would thin the blood. Just something to think about.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-2042299184390603972016-10-29T11:14:35.137+02:002016-10-29T11:14:35.137+02:00Kritika, since you are in India, trying Kutki shou...Kritika, since you are in India, trying Kutki should be inexpensive and then you will know if apocyanin helps.<br /><br />Calcium Folinate is also a potent antioxidant, but very different to NAC. It looks like some people without Cerebral Folate Deficiency, respond to Calcium Folinate and this might explain why. There are different types of oxidative/nitrosative stress and NAC will mainly help one type only.<br /><br />It really is all trial and error. There are lots of things you could try. If I lived in India, I would try Kutki.<br /><br />Galantamine does help some people. It is wise only to use what really helps substantially, otherwise you may well do more harm than good.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-6935318698628259342016-10-29T08:19:03.384+02:002016-10-29T08:19:03.384+02:00A big study on mitochondrial mutations in children...A big study on mitochondrial mutations in children with autism relative to their unaffected siblings came out today:<br /><br />https://www.sciencedaily.com/releases/2016/10/161028161729.htm<br /><br />I am posting the press release because there are actually two studies.<br /><br />The first study is a rather short read but very interesting in that the areas of the brain where they found the greatest pathological increase in lactate, also in many other studies I have read tend to pop up as hot areas for brain dysfunction (I have read a ton of them now). The cingulate gyrus (and its many subparts) does many things, but the anterior part of it (called the dorsal antererior cingulate gyrus or dACC) is involved intimately in a very important resting state brain network called the "salience network" which is thought to be involved in task switching, and in particular being responsive to environmental cues and helping to switch a person's brain from a default mode network bias (daydreaming, thinking of others, thinking about the future, self-related thinking) to a bias towards the central executive network (focus on some particular goal or action) and dorsal attention network (focus on what you see in front of you).<br /><br />Other brain areas such as the precentral gyrus (motor cortex which involves planning and executing movements) and the postcentral gyrus (somatosensory processing which includes touch, temperature, proprioreception) pop up pretty much all the time in imaging studies which is not a big surprise considering sensory processing issues tend to be a major comorbid set of symptoms associated with many if not most cases of autism.<br /><br />The superior temporal gyrus has many different functionalities but it tends to be a sensory integration area that binds all the senses together into a common percept. Also, depending on what range you define the STG to be, you could also include the auditory cortex as well as one of the primary speech processing areas in the brain often called wernickes area (these defined areas can be ambiguous in their boundaries depending on how a researcher might define them). These areas of the brain also tend to be core areas of disruption with respect to autisms core defined symptoms.<br /><br />Now why these brain areas seem to have greater mitochondrial dysfunction than others is not an easy answer and is along similar lines as to the question of why dopamine neurons in the brain are the first to be destroyed by Parkinson's disease when there is increasing evidence that mitochondrial problems in these dopamine producing cells may be what causes the cascade of dysfunction in these cells that eventually leads to their death. Why some areas of the brain are attacked more aggressively and why mitochondrial dysfunction occurs more in one part of the brain is a question for each and every neurological disease.<br /><br />I do know that there are thought now to be quite a few mitochondrial enhancing compounds and interventions (inducing autophagy via fasting for example) that would make sense to screen for, as addressing the deficits of a particular mutation or set of mutations likely requires a specific intervention. Some general purpose mitochondrial boosting compounds (nicotanimide riboside, methylene blue, rapamycin, to name a few) exist now, but most of the research I have seen does not cover any of these compounds with respect to autism (rapamycin though at least in some animals).<br /><br />Of course, mitochondrial dysfunction is always going to be a chicken and the egg problem until more is known about what developmentally goes wrong in autism, but that does not mean that focused attempts at a broad array of mitochondrial interventions should not be tried before giving up since there could likely be dozens of different mitochondrial genes that are mutated and it might take multiple mitochondrial interventions to get the ATP flowing again.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-89212968956872558512016-10-29T07:42:45.822+02:002016-10-29T07:42:45.822+02:00Hello Peter,
My son's cold and digestive issu...Hello Peter,<br /><br />My son's cold and digestive issues are getting better..the drugs and seasonal illnesses created such a behavioural cocktail that making sense of it becomes quite tiresome. I think in another ten days I will come to know of bumetanide is helping in any way.<br /><br />I have already procured diamox and thinking of ordering clonazepam also as it becomes easier to slip in a few prescription grade drugs camouflaged in a long list of OTC medicines. However, I do wonder how effective these may be in case bumetanide is not, although I understand diamox might have certain additional impacts.<br /><br />I would also appreciate your advice on trialling nootropics or those drugs used for CP, Parkinson's or Alzheimer's like citicholine or galantamine. Galamer is available as a very cheap drug albeit through prescription and I can probably persuade my son's paed as the online version seems expensive. I was thinking that these drugs might help those individuals more where some sort motor problems or issues like working memory, long term memory or executive skills exhist. My son does not have any of these issues. Although increased attention span would be a big boon.<br /><br />I have also been following with lot of interest your recent posts on CFD and inflammatory cascades<br />Do you see any indication for trying leucovorin in my son? We do have anemia in females of my family, I did not in my arrogance about my vitality take folic acid during the initial months of my pregnancy and my son is also anaemic. B12 and foliate?<br /><br /><br />What about apocyanin?<br /><br />My son behaves most normally when he gets up from sleep which I think is quite different from how your son behaves through the day. <br /><br />As usual, I have put together a long, rambling query. Would appreciate your suggestions.<br /><br />Regards <br /><br />Kritikanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-85367023882697279942016-10-28T19:34:00.130+02:002016-10-28T19:34:00.130+02:00Low dose aspirin, for those who tolerate it, is an...Low dose aspirin, for those who tolerate it, is an interesting anti-inflammatory strategy. I expect some people will benefit, just like some benefit from NSAIDs, but it may be different people. You would just have to try them. NSAIDs are not well tolerated by most people for long term use.<br /><br />I do not believe natural calcium channel blockers are anywhere near as potent as verapamil. There are many including the leaves of olive trees.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-4823002220892962752016-10-28T18:37:59.504+02:002016-10-28T18:37:59.504+02:00Great post. So much to think about. In your view...Great post. So much to think about. In your view do you think it is best to trial low dose aspirin for inflammation or reg/high strength ? Same for bipolar? In your view, is aspirin more promising than another NSAID like ibuprofen? Last, regarding verapamil -- do you think there are natural calcium channel blockers like magnesium that are as effective? Thanks! Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-50384615603817475082016-10-28T11:31:39.079+02:002016-10-28T11:31:39.079+02:00Kritika, this is all experimentation. It would be ...Kritika, this is all experimentation. It would be wise to check a small dose first to see if he has a negative reaction. Then use the higher end of the suggested dosage, so five drops three times a day. Try for a couple of days. If no response try a couple of days with a higher dose. If still no response, then assume the probiotic has no "autism" effect on your son. It seems that people who respond, do so very quickly, in our case, the same day. Your bacteria is a different one to the one I use, but people do report positive effects with it.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-63434591577685517072016-10-28T10:56:11.912+02:002016-10-28T10:56:11.912+02:00Thank you Christine for your comment and informati...Thank you Christine for your comment and information.<br />I absolutely agree with you.<br />As I read, in Greece has been made legal to produce industrial cannabis with no more than 0,2% THC and CBD will soon be available.<br />There is also an open debate, with lots of advocates, pressing for legal medical use.<br />I think systemic inflammation plays an important role in fear conditioning disorders our children are challenged by and possible treatments should be trialled.Anonymoushttps://www.blogger.com/profile/16138974464162606874noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-76949095062852775512016-10-28T09:39:13.997+02:002016-10-28T09:39:13.997+02:00Peter,
On the bottle it says five drops one to th...Peter,<br /><br />On the bottle it says five drops one to three times a day for someone over four years of age. This seems to be the standard dose. What could a higher dose be?<br /><br />I was under the impression that ten drops once a day for two days will give me an idea if he is a responder. In fact this impression was based on your opinion. <br /><br />Now it will take me another month to get another bottle and I can't order too many at one time as it was quite a formal process with undertakings and id proofs from our side to the company importing it from Canada.<br /><br />In short, it's a 15 ml bottle, what do you think constitutes a high dose?Anonymoushttps://www.blogger.com/profile/03480846227414561711noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-25402782071255310652016-10-28T09:25:35.205+02:002016-10-28T09:25:35.205+02:00Tyler,
Agree with you there and personally I woul...Tyler,<br /><br />Agree with you there and personally I would not even play with that idea but as you said one can't discourage a parent from trying it out as one of the final resort when faced with debilitating and potentially life threatening encephalopathies like dravet syndrome.<br /><br />That said, evidence for its actual efficacy remains largely anecdotal. Autism and anecdotal evidences seem to be best buddies.<br />Anonymoushttps://www.blogger.com/profile/03480846227414561711noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-32091445600405609002016-10-28T09:00:39.214+02:002016-10-28T09:00:39.214+02:00Kritika, if you give the standard dosage I do not ...Kritika, if you give the standard dosage I do not think the cold is an issue. If you give much higher doses then it would make sense to wait. Bioamicus told me that they thought the effect in autism comes with higher or more frequent doses.<br /><br />If you have just one bottle, better to wait for him to get better and then maximize the chance of a good trial.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-12964935876564967382016-10-28T08:26:01.948+02:002016-10-28T08:26:01.948+02:00Legal issues aside, I would avoid cannabis and can...Legal issues aside, I would avoid cannabis and cannabis related compounds because there is a lot of recent research lately into its effects in adolescents and teens as well as animals scaled to the same age of development that suggest nothing but bad occurs from exposure to exogenous cannabinoids. The other problem is that neuroscience does not have a real grasp on how cannabinoids work in the brain other than some guesses based upon behavioral changes. For example, I read a paper a few weeks ago that now shows that CB2 receptors are found in some areas of the brain (CB2 receptors are what help stimulate hunger in the digestive tract). This is new information as it was previously thought only CB1 receptors were active in the brain.<br /><br />Drugs like cannabinoids and opiates are very poor drugs except for some niche uses because they are so broad acting, and therefore will always come with undesirable side effects and very hard to predict impacts on human development. The most recent scientific evidence suggests right now that modern cannabis (which is far more potent than what the boomer generation smoked 30 years ago) is both physically addictive and that it acts as a permanent IQ and memory reducer in adolescents who use it (the studies on adults are mixed). If your child has intellectual disability, why would you want to give them a substance that causes even more intellectual disability.<br /><br />Politics aside, the endocannabinoid system is still very much undiscovered country scientifically, so who knows maybe in the future drugs targeting this system will be beneficial for a whole host of issues, not just autism. In the meantime, unless your child is having brain damaging seizures and nothing else has worked, it would be wise to avoid cannabis interventions until more is known about how they can work positively, because at the moment most of the objective news suggests that it is very bad stuff to put into your body and even worse to put into the body of a developing child.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-39955232654590416052016-10-28T07:00:10.203+02:002016-10-28T07:00:10.203+02:00Hello Peter,
I have received bioamicus reuteri bu...Hello Peter,<br /><br />I have received bioamicus reuteri but my son has come down with a cold. Can I start giving him the probiotic or wait for his cold to subside?Kritikanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-3962968742422410992016-10-28T06:47:52.276+02:002016-10-28T06:47:52.276+02:00Tanya,
Thanks. Yes, I think too many things happe...Tanya,<br /><br />Thanks. Yes, I think too many things happened at once. Weather change leading to sensitive stomach and then the nac and potassium. I have stopped giving him both and the sensory behaviour which I was erroneously linking to low potassium has also improved.<br /><br />But, the episode sort of unnerved me. He was standing all hunched up in pain on his toes. So basically I have got a lesson not to take things for granted.<br /><br />I will try the peppermint oil. Asfoetida also helps, orally as well as when rubbed on tummy or so they say.<br /><br />Regards Kritikanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-101323114670595962016-10-27T21:18:22.842+02:002016-10-27T21:18:22.842+02:00Kritika, I know that NAC, for some, can be hard on...Kritika, I know that NAC, for some, can be hard on the stomach - as well as potassium supplements (however, I give my son a combination of potassium bicarbonate and sodium bicarbonate and it helps his stomach in times of gut related histamine flare). Maybe since you were supplementing those it just flared things up a bit and since you've stopped, give it some time for things to go back to his normal?? Peppermint oil rubbed on his tummy might help him. Or some ginger tea? Hope he feels better soon. Tanyahttps://www.blogger.com/profile/01489962611979985947noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-51265091025165330172016-10-27T19:45:21.918+02:002016-10-27T19:45:21.918+02:00Hi Kritika,
In ancient Greece is well documented t...Hi Kritika,<br />In ancient Greece is well documented that they used cannabis, mostly for inflammation, in medicine, but it wasn't a part of recreational or religious life.<br />In 1890 cannabis was made illegal and only persisted in some remote rural areas. It is still illegal and the law is quite strict.<br />Greece is not a cannabis producing country, there are some minor exceptions of course.<br />I know from my grandmother that they made a kind of drink from poppy flowers, which grow everywhere, to keep babies calm while they were busy doing chores.<br />I think they actually gave their kids homemade opium.Anonymoushttps://www.blogger.com/profile/16138974464162606874noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-21033503305692566592016-10-27T19:33:38.971+02:002016-10-27T19:33:38.971+02:00Christine,
Thank you so much for all your valuabl...Christine,<br /><br />Thank you so much for all your valuable suggestions..have to note them down somewhere. And no, I have not tried any of these ideas before as I have been able to correlate his periodic stomach issues with his autistic behaviour so explicitly only recently. I had tried digestive enzymes generally after his diagnosis two years back but could not notice anything perceptible. And these problems are actually not perennial. In fact this is a season for virals, colds coughs and stomach issues for everybody. But as in your case, this period overlapped with me trialling NAC and bumetanide and it made isolating impacts of these drugs all the more difficult.<br /><br />But Christine, then I also thought that how effective these drugs may be if they act only in a narrow window of optimum environmental conditions and physical health. Its too confusing.<br /><br />One more thing, the slight disfluency that you observed in your son has been an issue with my son also for the past month or so..dont remember exactly. I do not think it's bumetanide or could it be..although I read the drug can cause speech problems in the elderly.<br /><br /><br />Do keep suggesting..I really am so grateful.<br /><br />Warm regards <br />Kritikanoreply@blogger.com