Editing advice from a friend
Editing advice from a friend
Feedback about my article draft agrees, too big for a paper, that is a chapter or two of a book. It did feel like two papers only somewhat related.
The advice - establish the premise, dive below the surface to see the history, flesh out the details, note others questioning the premise, close out with call to action. That fit neatly with the article format and started thinking about …
What is my point? --For this specific journal submission, a special supplement to a pharmacology journal focused on phytonutrients for nociceptive pain.
Abstract - establish the premise:
Pomegranate products help the acute nociceptive pain of histamine excess or Retinoid Toxicity and reduce long term degenerative risks.
Who may be at risk for undiagnosed histamine excess and/or retinoid toxicity is a separate subpoint. The case for kidney, liver disease, and schizophrenia and Alzheimer’s dementia being long-term risks of both is supporting evidence that histamine excess may be caused by Retinoid Toxicity – and that pomegranate can help those issues too. That Retinoid Toxicity may be caused by viral infection, vak injury and maybe in alcoholism and FAS, is also separate but adds to the point that histamine excess may be occurring in far more people than recognized – and when unrecognized, diet still loaded with vitamin A, leads to the degenerative risks of kidney, liver and brain damage.
Introduction - dive below the surface to see the history:
Histamine excess/Retinoid Toxicity is a problem with suicide as a risk, but long-term degenerative diseases may account for a higher percentage of deaths. Pomegranate can help the acute and long-term risks by inhibiting mast cells, and thereby reducing nociceptive pain and reducing hyperinflammation and oxidative stress damage. As a modulator it is low risk compared to previous efforts with histamine receptor agonists or reverse agonists or TRP channel inhibitors. Histamine receptors and TRP channels have too many wide-ranging effects throughout the body and negative side effects occur.
There are so many good reviews now and a peer-reviewed open access book about pomegranate that I should just list some briefly and the phytonutrients and benefits.
Known background about the ME/CFS and Retinoid Toxicity links to histamine excess could go in here and the comorbid conditions – the cannabinoid deficiency trend with Ehlers-Danlos – eat the pomegranate seeds too, they provide phospholipid content.
Sections - flesh out the details:
· What is pomegranate helping with in nociceptive pain and histamine excess or Retinoid Toxicity? TRP channels triggered by histamine, or stress or diet, etc, leading to endocannabinoid breakdown, (and cannabinoid deficiency symptoms eventually),
…leading to more translocation of channels to epithelial cell surfaces and increased hypersensitivity after stress or other causes, possibly <- that is my theory more than substantiated with a strong reference.
· Why are some people hypersensitive? Review possible causes of hypersensitivity.
Histamine excess leading to endocannabinoid release and breakdown leading to translocation of channels to epithelial cell surface- my theory.
Serotonin excess; dopamine excess – the chronic itch info; over-activation may lead to more expression of channels – capsaicin ointment occasional reports with higher dose patch; leaky gut/microbiome dysbiosis; gene alleles or nutrient deficiencies affecting metabolism or detoxification or channel metabolism or post-translational modification of proteins. Stress, mitochondrial dysfunction.
Bitter taste receptors, butyrate, TRP channels, kidney disease; polysialisis, prenatal ethanol, FAS & NCAM during development? How is that all related? à heterogeneity of many conditions? à
· How might congenital gene alleles be forming? Leaving some people with the phenotype of over-inflammatory, at risk for histamine excess. /Embryology and alcohol other toxins and retinoids, NCAM./ Possibly male alcohol use affecting the sperm is causing long-term excess retinoids in the liver, transported to the rest of the body. – another theory.
· What doesn’t help? Anything that triggers mast cells or adds to dietary histamine loads is adding risk. Vitamin A and carotenoids would only be additional risk if over activation is occurring – potentially if liver injury is suspected, ME/CFS or history of viral infection, vak or drug injury/akathisia, alcoholism is present or possibly in FAS or ADHD, schizophrenia or Alzheimer’s dementia possibly. Glyphosate does not help bacterial species, as it is antibiotic in nature. Microbiome dysbiosis is a risk. And other risk factors of modern life graphic/Table.
· What might help? Preventing pain/inflammatory triggers in the first place. Learning to recognize the hammers your patients are banging their own thumbs with. Recognizing the cause of pain is powerful knowledge, then the underlying dysfunction may be correctable.
Treating acute symptoms with mast cell inhibiting, Nrf2 promoting, antioxidant rich pomegranate and/or synergistic products that include mitochondrial support nutrients and calming amino acids can help while histamine excess is not yet under control. Reduce the pain by reducing the problem – inhibiting mast cells - and also preventing oxidative stress chemicals from adding more inflammatory signaling with the immunomodulatory and Nrf2 promoting antioxidant benefits of pomegranate. The pomegranate contains antioxidants and promotes our own production of glutathione. Promoting Nrf2 is also inhibiting NFkB as the pathways share a Clock protein and pomegranate peel has been shown to inhibit NFkB and to promote Nrf2, along with many other nutrients also.
Niacin helps – section on what else helps? Relevant to pharmacology as a pitch for synergistic products perhaps? That mitochondrial dysfunction is part of the long-term risks and fatigue and pomegranate and Nrf2 promoting foods can help? Pomegranate helps the microbiome, use of inner pith fiber would help too. The microbiome makes butyrate for us and can make urolithin A and B. Pomegranate helps promote butyrate producing species. Mitochondria are also bacterial in nature.
Add cholesterol – the post-translational modification issue – needs cholesterol to work right – to prevent misfolded proteins. It is somewhere in the earlier Substack posts, misfolded protein section I think.
Keep Self-injury info in there for general awareness and accessibility in a paper about a condition with suicidal urges, and because emotional dysregulation also requires cognitive training in coping? Stress itself is a hammer?
Discussion - note others questioning the premise,
The bulk of research on pomegranate is quite positive, the biggest problem is that it is still in early adopter phases of establishing the market. There are only a few products available as supplements and adulterants can be a problem. There is a need for quality production of pomegranate for use of peel and separation into inner pith and outer rind increases the potential uses. The pith is milder in tannins than the outer rind and richer in beneficial fiber, and helpful as a functional food. The outer rind is more concentrated in the medically potent ellagitannins and other phenols and would be useful in extracts or for synthesizing tannins or antioxidants for industrial applications.
Again - the idea that Retinoid Toxicity is being caused by jabs or virus is a separate hypothesis than the idea that pomegranate peel or fruit can help symptoms and long-term risk of histamine excess and Retinoid Toxicity. Discussion of that theory doesn’t belong in this proposed paper. Within this paper it is being presented as a possible cause for histamine excess and therefore a potential group of people in need of pomegranate or other help.
Addition regarding Fetal Alcohol Syndrome and the heterogeneity that is seen with many congenital conditions, autism, and schizo-affective disorder.
Retinoic acid is activated excessively during alcohol use leading to low in active vitamin A and excess active retinoids that shipped throughout the body. It effects DNA and can affect fetal development via the father’s damaged sperm or the pregnant mother’s use of alcohol.
Discussion - Problem – the work on FAS has focused on female drinking as the cause and less on what male drinking does to the sperm – which is half the infant’s DNA – while the mother’s drinking is affecting morphogenesis directly, her ovum would have not been formed during her drinking. It was formed during the woman’s fetal development – was grandma a drinker too? And what about grandpa? We need generational research regarding Fetal Alcohol Syndrome. Also, socio-economic factor to consider – if a woman drinks alcohol prenatally, chances are good that her partner is also a drinker. While some women may be isolated drinkers, it is common for a couple to share a habit and males tend to drink more alcohol than women on average and can handle more based on average body size differences. If something is likely to be happening, the effects should be studied. The adult population of FAS has had little research or support for their ongoing needs which seem to include degeneration into worse mental and physical health – something is still wrong for them – could it be Retinoid Toxicity remains from alcohol effects on the sperm from their fathers?
Epigenetic and gene alleles are likely in the sperm of men who use alcohol, niacin deficiency is likely, membrane breakdown from oxidative stress (ROS) risking damage to kidney, lung and sexual glands. Antioxidant support with vitamin C, cysteine, and methionine, were protective in an animal-based study. (Amanverez, 2005), (Pourmasumi, et al, 2017) Acute or chronic alcohol use causes oxidative stress and can cause genetic or epigenetic changes in sperm that can affect the offspring. (Carrell, 2013) Reversible loss of mitochondrial DNA was seen in an animal based study with ethanol or lipopolysaccharide. Antioxidant supplements of melatonin, vitamin E, and Coenzyme Q10 promoted adaptive resynthesis of mtDNA after ethanol administration, (anima-based study). (Alexeyev, 2011)
Conclusion - repeat the premise and findings, close out with call to action:
Pomegranate products can ease the emotional dysregulation of histamine excess within 20 minutes [personal experience] and help protect against long term risks associated with chronic MCAS or Retinoid Toxicity. The availability of quality pomegranate products available as pharmaceutical products or functional foods are limited and there is a growing need with LongCovid and ME/CFS populations as possible consumers in need of mast cell inhibition and Nrf2 promotion.
//I really want people to know that suicidal urges from histamine excess are not the person in their rational mind and they really need help not condemnation for being out of control, weak, or angry. Their brain is an itchy mess of whirling over-active thoughts – and a small glass of pomegranate juice can calm that within 20 minutes [personal experience].//
Good night, sleep in peace!
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