Going out on a limb - #25 - excess Glyphosate. #26 - Microbiome health. #27 - low Tryptophan
It is a really big limb though. Glyphosate was developed as an antibiotic and our microbes include bacteria. Our microbes can directly affect brain health.
Research focused on Alzheimer’s dementia found that glyphosate can cross the blood brain barrier and it causes elevated TNF-alpha, (1), which would increase NF-kB and the hyperinflammation positive feedback loop. (3)
Changes in the gut microbiome caused by glyphosate’s antibacterial effects can directly affect brain amyloidosis and has been associated with many mental health conditions including schizophrenia. (2)
“Alterations to the gastrointestinal microbiome have been associated with multiple neuropsychiatric and neuroinflammatory disease states, including anxiety, depression, Alzheimer's, and Parkinson's disease (5, 6).” (2)
“Both glyphosate and glyphosate-based herbicide exposure have been shown to decrease members of the family Ruminococcaceae (45). Reductions in Ruminococcaceae within the gut microbiome are implicated in multiple neuropsychiatric disease states, including Parkinson's disease (46), Schizophrenia (47), depression (48) and modulate social behaviors in rodents (49). Members of the family Ruminococcaceae produce a variety of metabolites that can alter mood and behavior, including L-glutamate. The amino acid L-glutamate mediates communication between the gut and the brain in several ways.” (2)
The microbe “family Ruminococcaceae” (2) helps gut health by producing L-glutamate, a free amino acid, which has multiple roles in the gut and brain. The Vagus nerve is a direct conduit between the two and chemicals do pass between the brain and gut. Other beneficial species, “including Clostridium sporogenes and Lactobacillus spp.”, (2), that may be lost to glyphosate effects, produce a metabolite from the amino acid tryptophan, “3-Indole Propionic Acid (IPA). (2) IPA helps prevent misfolded proteins which are seen in Alzheimer’s dementia, autism and other neurodegenerative conditions.
“…certain commensal microbiome members, including Clostridium sporogenes and Lactobacillus spp., can metabolize tryptophan into compounds such as 3-Indole Propionic Acid (IPA) and Indole-3-Aldehyde (I3A) (15). IPA is a potent neuroprotective antioxidant that decreases activation of glial cells and astrocytes, prevents DNA damage, and inhibits beta-amyloid fibril formation, the primary contributor to the pathogenesis of Alzheimer's disease (15). I3A acts on the aryl hydrocarbon receptor (AhR) within intestinal immune cells, resulting in increased IL-22 production, a key cytokine in maintaining mucosal homeostasis, by playing a prominent role in inflammation and tissue regeneration (15).” (2)
“Additionally, metabolism of glyphosate by the microbiome may alter NMDA receptor activation thereby promoting neuroinflammation in otherwise healthy individuals.” [NMDA over activation would be a risk to the hippocampus and could lead to Alzheimer’s eventually.]
“Glyphosate-induced perturbations to the gastrointestinal microbiome may influence the synthesis of many neurotransmitters, necessary for mental health and wellbeing, encourage the formation of damaging ROS and reduce bacteria thought to be beneficial during times of stress.” (2)
The list is bigger too. (With my answers as example participant #one, see post - Solutions - How did I get better?)
Revised Check List
(#1) Yes - Low vitamin D (can also be
(#1 & #6/Trace mineral imbalance) Yes - Low magnesium or
(#25 & #1) Yes - Excess Glyphosate - helped to cut it out, thoroughly, or
Yes -Gene differences in the Vitamin D Receptor (VDR). (47) also seen in bipolar disorder (48) toxoplasmosis risk (76)
(#20 & #1) Yes - Excess Retinoic Acid might affect Vit D Receptor & other receptor’s transcription of proteins. (114) Either deficiency of retinoids (Vitamin A and beta and some other carotenoids) or excess Retinoic acid can be a causal factor in symptoms of schizophrenia. (114, 116) See post #20.
(#2) Yes - Low iodine/hypothyroidism / excess fluoride, bromide and perchlorates. (55)
(#2 & #20) Yes - thyroid & Retinoic acid link - Excess Retinoic Acid might affect Thyroid Receptor function. (114)
(#3) Yes - Zinc deficiency prenatally
(#3) Yes - or zinc deficiency later in life. (69, 70, 71, 72, 73)(114) Pyroluria seems a genetic cause for me.
(#4) Yes - Excess copper in relation to a low zinc level - may be dietary
(#4) Unknown - gene issues in copper transport - or genetic - the copper/zinc transport protein dysbindin would be needed as a treatment if that was an underlying factor. (Dysbindin:56, 57, 58, 81),
(#5) Unkown - Low manganese and iron were found along with elevated copper. (80, 57)
(#6) Yes - (low selenium and zinc, probably elevated copper, marginal to okay iron) - Low trace minerals or excess, or imbalance - it is complex - (83)
(#7) Unknown - Low Cesium is also seen in Alzheimer’s. The research team speculate that it may chelate misfolded proteins. (83) [Regarding the #s - there are lots of trace minerals, this is still an initial look at the size of the problem.]
(#8) Yes - low folate/B12 methyl B vitamins, dietary – or
(#8) Yes - gene methylation difference and/or - Yes - pyroluria may be factors in chronic deficiency. Low methyl folate and methyl B12; possibly methylation gene differences. (55)
(#9) Unknown but seems likely elevated Crp level - Low B6, folate and methyl B12 can lead to increased C-reactive protein levels which is associated with schizophrenia. (46, 55)
(#10) Yes - low B6 - the pyroluria causes this for me. - Low B6, (82)
(#11) Yes - low Inositol -supplements help and are needed at least every other day or so or symptoms start returning. - B6, B8 (Inositol), and B12 supplementation helped. (85)
Yes - (#23) B1 deficiency, most likely seen with severe malnutrition.
(#12) Yes - Low niacin (B3) – or need for more than average for an unknown reason. (45) The reason might be that it preserves tryptophan to be used for other things, like our microbiome and serotonin. “Dietary components including tryptophan, glutamate and complex carbohydrates serve as a substrate for many bacterial metabolites. Amino acids, including tryptophan and glutamate, serve as precursors in synthesizing many neuroactive substances, including kynurenine, serotonin (5-HT), dopamine, gamma-aminobutyric acid (GABA) and epinephrine (12, 13). Enterochromaffin cells within the intestinal epithelium are the primary producer of gut-derived 5-HT. Tryptophan metabolites are vital precursors in the synthesis of kynurenine and 5HT within the gut.” (2)
(#27) Out here on the limb - I’m adding tryptophan - adequate protein!
(#13) Yes - Vit C too low can cause easy bruising - Vitamin C supplementation helped, (88)
( #14) Yes - ALA I added that early in my Get Better Journey and have stuck with it - Cofactors: Alpha lipoic acid helped, “(100 mg/d) for 4 months”(86)
(#15) Yes - CoQ10 - I do find CoQ10 helpful too and have it used it for many years - CoQ10 supplementation found no difference – adherence may have dropped off. (87)
(#16) Adequate protein diet will provide enough cysteine for most people - N-acetylcysteine – an amino acid, used to form glutathione, along with glycine and glutamate. Doses of 600-1000 mg once or twice a day were used. (91) Also see NAC – N-acetylcysteine.
(#17) Yes - Low DHA/EPA, omega 3 fatty acid: (43)
(#18) Yes - externally induced- high THC marijuana with no CBD for too long for my medical use - too much THC alone can worsen rationality or genetic…
(#18) No - my gene difference causes low levels of both 2-AG and anandamide. Gene difference leading to - Low 2-AG (CBD equivalent) in relation to anandamide (THC equiv.). (49) (50) (75) (51, 77) (52)
(#19) Unknown - Glutathione levels were found to vary, (88) Nrf2 promoting phytonutrient foods or supplements would be helpful.
(#21) Yes - Psych med history, use and withdrawal - See post #21.) -
(#22) Yes - Psychosomatic symptom history and childhood ACEs or other trauma history. See post #22. I discussed my history and recovery strategies in that post. This post, part 3 of a series on Moderation includes child trauma and ACEs information.
(#24) Yes/& likely prenatally. (My mother had lifelong symptoms too and now has Alzheimer’s but has improved on a low histamine diet with methyl folate supplements and some herbal and medication antihistamines and pomegranate juice! and CBD drops.) - Histamine intolerance prenatally during fetal development, and/or currently as a child or adult.
Yes - (#26) Poor gut health - Microbiome. Digestive issues have been a problem for me, including occasional SIBO like symptoms - overgrowth, or years of leaky bowel like problems and more food sensitivities, migraine triggers, and autoimmune molecular mimicry issues. (Molecular mimicry - Gut protein that is undigested and similar to a body protein is allowed through a poorly defended gut wall whole, and white blood cells set up antibodies that attack it and the similar self-proteins.)
Clearly this is complicated and difficult for someone with a college or medical degree - or a neuroscience advanced degree - so it would be very difficult for someone already experiencing mental health problems.
I will repeat - this is about suicide risk in young people and potentially now in the CoV vakked. Histamine excess is someone who is not themselves currently, and if it is a daily diet, for years, then it may seem like that is their normal self - but it might not be with some big changes.
I am glad to have survived histamine excess while not knowing what was wrong, and while mostly being told that I was just in need of psych meds or talk therapy. Talk therapy did help some and I did have some psychosomatic symptoms - working through that process was a need too. Depending too much on lab tests can miss a lot of things that standard lab tests don’t screen for. Or they may be inconclusive as a diagnostic standard but are treated as if the negative result does mean that the condition is not the problem.
Condolences to anyone who has lost a loved one to self-harm of some sort. Irrational is hard to cope with for the strongest people, smart, brave, caring - if the brain chemically imbalanced then it can cause extreme changes. Please don’t try to rationalize actions that may have been very irrationally based at the time.
The checklist is a list of things to avoid, genetic problems to screen for, and nutrients to obtain in adequate and balanced amounts - daily or very regularly. Adequate sleep and water are also needs, and blackout curtains or an eye cover at night. Social connection and some sense of purpose, ideally within a small team would also be very helpful for mental health and for reducing inflammation of emotional stress.
Since the checklist is so difficult - to be blunt - a live-in facility would be ideal for people who are already experiencing brain fog or extreme anxiety or irrational thinking. Self-care is too difficult when the care is so detailed. Histamine excess requires many varied diet restrictions and retinoic acid excess would require even more.
I will repeat - pain hurts, health is better. Health is worth the work, in my opinion, but healthy people may need to do some work for unhealthy people to help them regain their own better health.
Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.
Reference List
New study shows that commonly used herbicide crosses blood-brain barrier, July 28, 2022, asu.edu, https://news.asu.edu/20220728-new-study-shows-commonly-used-agricultural-herbicide-crosses-bloodbrain-barrier
Barnett JA, Bandy ML, Gibson DL. Is the Use of Glyphosate in Modern Agriculture Resulting in Increased Neuropsychiatric Conditions Through Modulation of the Gut-brain-microbiome Axis? Front Nutr. 2022 Mar 8;9:827384. doi: 10.3389/fnut.2022.827384. PMID: 35356729; PMCID: PMC8959108. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959108/
Schütze S, Wiegmann K, Machleidt T, Krönke M. TNF-induced activation of NF-kappa B. Immunobiology. 1995 Jul;193(2-4):193-203. doi: 10.1016/s0171-2985(11)80543-7. PMID: 8530143. https://pubmed.ncbi.nlm.nih.gov/8530143/