Link to Niacin/wild hamster cannibalism/glyphosate and a list of Glyphosate posts, with a CoV theme.

Expanded last post: Niacin deficiency linked to glyphosate and cannibalism (in wild hamsters). ( I posted that link before I was done watching the video, and slept a little more after watching it. So now the post has the hamster story in more detail and some other info from the video webinar. Each of the four speakers had significant info that added to the bigger picture.

What I didn’t include in my rewrite was that action individually is being encouraged – informing the government isn’t working or what they claim to be doing is on a too long-time scale – status quo to continue until some future date.

We are in a corporatocracy, an oligarchy, and corporate profit is protected over individual consumers. Our buying power collectively may be our biggest voice. If the consumers stop buying the poisonous products more producers might switch to organic foods. However – with the government complicit – they buy a lot of food and provide a lot of school children on Free or Reduced-price meals with two and sometimes three meals a day. Our individually stopping the purchase of RoundUp ready crops or meats raised with them – will not stop the big bucks that agribusiness gets from government purchase for schools, VA hospitals or facilities, or the military. Anyone on a cafeteria meal-plan will likely be getting glyphosate foods.

brown mouse on brown wooden table
“Teddy, my Syrian Hamster.” Photo by Andy Holmes on Unsplash

Glyphosate disrupts actin which is like a scaffolding with a crane that can direct activity and line up vital chemical parts within the cell. Glyphosate disrupts the crane’s ‘hook’.

Series – glyphosate is a big deal and has been since around 1965, use greatly increased sometime between 1985 and 1995:

  • Glycine & glyphosate & misfolded proteins – Seneff article. (June 13, 2021)
  • Covid-19 “broken glass lung” and glyphosate, draft (March 4, 2021), posted (Dec 17, 2022) *This is/was a follow-up to Glyphosate & COVID19, (Oct 25, 2020)
  • Glyphosate increases histamine, both may be a factor in COVID19 (Nov 10, 2020)
  • Glyphosate & COVID19, (Oct 25, 2020) *Biofuel made with RoundUp biomass is producing increased glyphosate residue in the air of communities near the biofuel production facility and in areas that now use a lot of biofuel in their gasoline mix. This post has a link to a company where you can self-order a screening test for glyphosate residue (in a urine sample I think).
  • Glutathione, Nrf2, Autism & Glyphosate, (May 26, 2018)
  • A US Congressman [Ted Lieu] is concerned about safety of glyphosate, (March, 19, 2017) Excerpt from the brief post: “An employee of the EPA may have colluded with Monsanto to suppress investigation of the safety of glyphosate and the herbicide Roundup.” (My words, link to a article in the post).
  • Glycine, Cheerful Juice, and testing for glyphosate, (Oct 26, 2016) *One of my solutions is to take powdered Dimethylglycine in water with a little sweetener, smidge of baking soda to offset the acidity, and a little juice for flavor. It can taste a little like red wine. Acidic citrus juices are not as helpful as a little blueberry, pomegranate or cherry juice. This post has links to previous posts I had written about DMG and my ‘Cheerful Juice’ – it makes me more cheerful but can taste kind of bad without the extra additions.
  • Glyphosate and disruption of the protective mucus layer made by coral species. *an old draft post that I just posted, (Oct 19, 2016) (Dec 17, 2022)
  • The herbicide Round-Up found more dangerous than glyphosate alone, (Oct 17, 2016)
  • Glyphosate, a consensus statement; a link, (Sept 21, 2016)
  • Updates regarding glycine, health, and glyphosate, (Sept. 20, 2016)
  • Glyphosate was found in vaccines; and tips for reducing dietary exposure, (Sept 16, 2016)
    • *Gelatin from commercial sources is likely also a source of glyphosate residue as collagen is a protein made with a lot of glycine – leaving a lot of opportunity for glyphosate to be substituted instead in an animal fed RoundUp crops as feed. This would make gelatin capsule supplements a negative and any collagen joint support products that use commercially sourced collagen instead of organically raised sources.
  • Glyphosate was created as an antibiotic and mineral chelator but is being used as an herbicide, (Aug 2, 2016)
  • CYP enzymes are needed to produce both 25 vitamin D and 1, 25 hormone D; and more on glyphosate, (June 29, 2016)
  • There is never going to be a good time to say that glyphosate is unhealthy, (June 17, 2016). This post is more about how society ignores some people, the second in command in the airplane, and that can lead to big crashes. I bring up the infertility aspect of glyphosate in this post, and that it is likely part of the increase in gender dysphoria.
  • Vitamin D activating enzyme and Glyphosate, the herbicide Roundup, (June 14, 2016)
  • Vitamin D, Cholesterol sulfate, concussions, and glyphosate (Round-up), (June 11, 2016)

Glyphosate would be causing a DNA female fetus to develop male pattern instinctual behaviors – rougher active play as a child and mounting dominance behavior when sexuality is developing rather than bending over and wanting to submit. Gender dysphoria is very real and occurs in the prenatal hormone environment of an infant when there is a mismatch between the uterine hormones that are predominant and the fetal DNA sex.

Historically, male DNA with female gender behavior was more common, though rare still. A pregnant woman is female and has female hormones, so it makes sense. Endocrine mimetic pesticides and BPA are likely increasing the incidence of male DNA babies that grow up with female gender behavior instincts. The glyphosate is newer to human history and now there is a big increase in female DNA babies that grow up with male gender behavior instincts. There is also social pressure on young girls and woman to be very overtly sexual, or maybe skip it by transitioning to male. Join the fun LGBTQIA+ marginalized group and give up your ‘white privilege’ – along with your healthy body, normal function sexual parts, and ability to have a baby or breast feed it…. This is not a solution to reducing glyphosate or estrogen mimetics in our food supply and environment.

We, humans, are causing trans or homosexuality in other species too. It makes me embarrassed for humans and sad for other species and the planet as a whole. We are a blight on this planet.

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.

Covid-19 “broken glass lung” and glyphosate

The HO-1 enzyme that may be being made wrong, with glyphosate in place of glycine, promotes another chemical (granulocyte macrophage-colony stimulating factor (GM-CSF) that is seen to be elevated in Covid-19 (1) and the receptor for the chemical may be involved in a lung condition (2) that also has “broken glass” like lung images. The unusual lung images are due to the alveolar areas to be fluid filled and dysfunctional, opaque white areas in the images instead of black/air filled cavities that would normally be visible. (2)

PAP – Pulmonary alveolar proteinosis – “broken glass” lung, or “paving tile”.

The “broken glass” lung issue is also called pulmonary alveolar proteinosis (PAP). (2, 3)

Medical opinion: “Clinical data, analytical findings and the few pathological references we have so far suggest SARS-CoV-2 lung disease could be a secondary interferonopathy with pulmonary alveolar proteinosis (PAP)-like features and sometimes thrombotic microangiopathy.” (3)

Treatment with Interferon inhibitors might provide “IFN-γ blockage” and medication trials were recommended.

The presence of PAP suggests alveolar macrophage dysfunction in clearing surfactant from the alveoli. Whether IL-18 or IFNγ blockage and/or treatments aimed at increasing surfactant phagocytosis/processing by alveolar macrophages are viable treatment strategies, needs further exploration.” (3)

Take home point from clinical trial information and an Abstract-less paper: the PPAR-gamma activator Pioglitazone helped reduce the size of alveolar macrophages in autoimmune pulmonary alveolar proteinosis (PAP). (Vis, Kelly, De Heuvel, MacEachern, 2020) (CTG Labs/NCTO3231033)

GM-CSF promotes growth of alveolar macrophages.

COVID-19 is a clinical syndrome ranging from mild symptoms to severe pneumonia that often leads to respiratory failure, need for mechanical ventilation, and death. Most of the lung damage is driven by a surge in inflammatory cytokines [interleukin-6, interferon-γ, and granulocyte-monocyte stimulating factor (GM-CSF)]. Blunting this hyperinflammation with immunomodulation may lead to clinical improvement. GM-CSF is produced by many cells, including macrophages and T-cells. GM-CSF-derived signals are involved in differentiation of macrophages, including alveolar macrophages (AMs).” (1)

The authors go on to explain that some GM-CSF can be helpful and promote growth of alveolar macrophages while too much of the GM-CSF stimulation is not. Trials are underway with medication to either block the receptors or antibody medication that combines with the free floating GM-CSF in the blood stream so it is no longer available. (1)

This blockade can be achieved through antagonism of the GM-CSF receptor or the direct binding of circulating GM-CSF. Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. “

Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies…HO-1-dependent heme catabolism, regulates GM-CSF synthesis in human airway..”

PPAR-gamma activation helped autoimmune PAP. (Vis, Kelly, De Heuvel, MacEachern, 2020) (CTG Labs/NCTO3231033) See Figure 3, the PPAR alpha, beta/delta, and gamma activate different functions in normal health. Figure 5 shows natural and synthetic ligands of the PPAR receptors, (Grygiel-Gorniak, 2014), but fails to include 9-cis-Retinoic Acid. It was found that both a synthetic and a natural agonist of PPAR gamma only had the desired anti-inflammatory effect when 9-cis-Retinoic acid was also present. (Worley, et al., 2003)

Use of a retinoid medication for a type of leukemia can cause an adverse reaction syndrome that include “ground glass lung” scans.  (Weerakkody, et al, 2012)  See this post for more info and the full citation: microRNA, elevated homocysteine and is there a role for excess Retinoic Acid? ( I think there is a role for excess active retinoids in COVID19 and hyperinflammation that seems to be related to the “ground glass lung” scans – fluid filled alveoli – patients drowning in their own body fluids.

We would need to find out if there is an aberrant form of the HO-1 enzyme containing glyphosate in its amino acid construction, that is functional in some new aberrant way, possibly promoting too much GM-CSF – causing a change in the function rather than just making it dysfunctional.

Regulation of IL-1 beta-induced GM-CSF production in human airway smooth muscle cells by CO [Carbon monoxide] — retracted article – need to rethink/read more, * “The American Physiological Society is retracting this article due to inclusion of data in Figure 4A that were published previously in Figures 5 and 6 of the article “Carbon Monoxide Inhibits Human Airway Smooth Muscle Cell Proliferation via Mitogen-Activated Protein Kinase Pathway” (https:// and represent different results. Due to the length of time since initial publication, the authors were unable to provide original captures for these experiments to resolve the concerns.” (Retraction statement) **So, ignore Figure 4A.

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

  1. Bonaventura A, Vecchié A, Wang TS, et al. Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies. Front Immunol. 2020;11:1625. Published 2020 Jul 3. doi:10.3389/fimmu.2020.01625
  2. Borie R, Danel C, Debray M-P, et al., Pulmonary alveolar proteinosis. European Respiratory Review 2011 20: 98-107; DOI: 10.1183/09059180.00001311
  3. Julián Fernández-Martín, Pérez-Álvarez Roberto and Lamas-Barreiro José María, COVID-19: An Acute Secondary Interferonophaty? The Mirror of Autoinflammatory Syndromes. Arch of Immunology, Vol 2, Issue 1, DOI: 10.36959/885/368
  4. Mair, K.M., Robinson, E., Kane, K.A., Pyne, S., Brett, R.R., Pyne, N.J. and Kennedy, S. (2010) Interaction between anandamide and sphingosine-1-phosphate in mediating vasorelaxation in rat coronary artery. British Journal of Pharmacology, 161 (1). pp. 176-192. ISSN 1476-5381
  5. Giacoppo S, Mazzon E. Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?. Neural Regen Res. 2016;11(12):1896-1899. doi:10.4103/1673-5374.197125
  6. ARN14988 (aCDase Inhibitor),
  7. Xiao Mei Wang, Hong Pyo Kim, Kiichi Nakahira, Stefan W. Ryter and Augustine M. K. Choi, The Heme Oxygenase-1/Carbon Monoxide Pathway Suppresses TLR4 Signaling by Regulating the Interaction of TLR4 with Caveolin-1. J Immunol March 15, 2009, 182 (6) 3809-3818; DOI:
  8. Rebecca Gilbert, Update on COVID-19 and Parkinson’s Disease. Oct. 27, 2020,,
  9. Fukushima T. Niacin metabolism and Parkinson’s disease. Environ Health Prev Med. 2005;10(1):3-8. doi:10.1265/ehpm.10.3
  10. Francisco Navarrete, María Salud García-Gutiérrez, Rosa Jurado-Barba, et al., Endocannabinoid System Components as Potential Biomarkers in Psychiatry. Front. Psychiatry, 27 April 2020 |
  11. Erukainure OL, Matsabisa MG, Salau VF, Islam MS. Tetrahydrocannabinol-Rich Extracts From Cannabis Sativa L. Improve Glucose Consumption and Modulate Metabolic Complications Linked to Neurodegenerative Diseases in Isolated Rat Brains. Front Pharmacol. 2020;11:592981. Published 2020 Nov 24. doi:10.3389/fphar.2020.592981
  12. CK Eternity, Melatonin: the master antioxidant. August 9, 2020,,
  13. Yingying Lu,Baixia Hao,Richard Graeff &Jianbo Yue, NAADP/TPC2/Ca2+ Signaling Inhibits Autophagy.
  14. Article: e27595, Published online: 08 Jan 2014,,
  15. Li R, Li Y, Liang X, Yang L, Su M, Lai KP. Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets [published online ahead of print, 2020 Nov 10]. Brief Bioinform. 2020;bbaa300. doi:10.1093/bib/bbaa300
  16. Tweet Thread
  18. / pdf

Glyphosate and disruption of the protective mucus layer made by coral species.

Excerpt – glyphosate entering the ocean may chelate manganese and leave coral unable to form their protective layer of mucus containing sulfated glycoproteins: “A protective layer of mucopolysaccharides called mucus is secreted by corals, and it has been characterized as containing sulfated glycoproteins similar to chondroitin sulfate, [44] which play an important role in controlling pH and the transepithelial movement of electrolytes and water, just as is the case in vertebrate mucosa. Mucus pathology is implicated in coral disease leading to mortality, particularly in the Caribbean.[219] Thus, an interesting hypothesis that should be considered is that glyphosate chelation of Mn is a crucial factor in the worldwide coral die-off.” (Samsel, Seneff, 2015)

Manganese is important:

Vitamin D deficiency has reached epidemic proportions in the US and increasingly around the world in recent years. [124] In a large population study in the US, Bodnar et al. [34] found deficient levels of vitamin D in 83% of Black women and 92% of their newborns, as well as in 47% of White women and 66% of their newborns, despite the fact that over 90% of the women were on prenatal vitamins. This deficiency is associated with an increased risk to bone fractures, likely due to impaired calcium homeostasis. [145] It is even likely that care-takers are being falsely accused (“Shaken Baby Syndrome”) of abusing children in their care who suffer from bone fractures. [255] These children are highly vulnerable to bone fractures due to impaired bone development. Bone fractures in the elderly due to osteoporosis have also risen sharply recently in the industrialized world. [139] The cause of a surging incidence of hip fractures across multiple age groups remains a mystery to medical personnel. [140]

Samsel and Seneff [248,249] proposed that the current vitamin D deficiency epidemic is caused by glyphosate, due to glyphosate’s interference with CYP enzymes. The metabolite that is usually measured, 25-hydroxy vitamin D, is the product of activation in the liver by a CYP enzyme that is also critical in bile acid formation. However, there is a larger problem with bone development due to impaired Mn homeostasis.” (Samsel, Seneff, 2015)

Selenium is also important (selenoproteins):

Dopamine suppresses thyroid stimulating hormone, and therefore dopamine insufficiency can lead to overactive thyroid and potential burnout of the thyroid gland. [270] This problem is compounded by the fact that thyroid hormone itself is derived from tyrosine, one of the three aromatic amino acids that are negatively impacted by glyphosate through disruption of the shikimate pathway. The thyroid gland also depends critically on selenoproteins as antioxidants. [249] Glyphosate’s depletion of both selenium and methionine will lead to reduced bioavailability of selenoproteins. It is conceivable that all of these factors working together can explain the strong correlation of glyphosate application to corn and soy with thyroid cancer [Figure 7], as well as the association between maternal thyroid disease and autism. [238]” (Samsel, Seneff, 2015)

Glutathione is depleted, Manganese is needed for its production, along with other nutrients and Nrf2 promotion and/or a healthy circadian cycle:

Experiments exposing immature rats to Roundup®, whether via exposure to the dam during pregnancy and lactation or via acute exposure to the pup for 30 min, demonstrated lipid peroxidation and NMDA receptor activation in the hippocampus, indicative of oxidative stress and glutamate excitotoxicity. [59] Acute exposure increased the release of glutamate into the synaptic cleft, and depleted GSH.

Glutamine synthase depends upon Mn as a cofactor, so depleted Mn supplies would lead to a build-up of glutamate that cannot be returned to the neurons using normal channels. Multiple sclerosis is associated with both depleted Mn in the cerebrospinal fluid [185] and depleted GSH synthase in the white matter lesions. [309]” (Samsel, Seneff, 2015)

Why should we care about coral? Because we and coral have similar biological pathways. Nature loves a good design and sticks with it across the plant and animal and microbial kingdoms. Also it would be better to be good stewards of the planet, instead of being an invasive parasite that destroys everything in its path.

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

(Samsel, Seneff, 2015) Samsel A, Seneff S. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies. Surg Neurol Int. 2015 Mar 24;6:45. doi: 10.4103/2152-7806.153876. PMID: 25883837; PMCID: PMC4392553.

Sorry for the disruption in site service (my fault); Cancer, POTS, Epigenetics & the One-Carbon Methylation Cycles.

I missed an email. Problem now fixed.

I have been very busy with the pomegranate paper, and sadly, or not surprising, it was not accepted for further review – non-standard, which is true. It was too long and I learned more while researching for it and needed to rewrite the main article. A book or website with guided pages and some screening questions to help guide people to material that may be helpful is my plan.

My goal is to make a more concise site with a dropdown menu of some sort to help guide people to the info that they want or need – and some screening question sections to help pinpoint which information may be needed. I have started a very preliminary ( but got hung up on how to add images. It says just “drag and drop” and I have no idea why that doesn’t seem to work. Is that an Apple thing? ** I figured out how to drag and drop an image but then I couldn’t move it to any other sections. WorkFlowy may not be for me.

I have been posting on SubStack and need to post here more. I have posted a few new things to, but an older post was most read in November so that may have been Oct or even longer ago. The images in this post are some of my travel pics. Peace is mental and physical. ( It is not a long post but has some good starting points. Build mindfulness, peaceful brain pathways and try to forget stressful worry pathways by not thinking about them. One anxiety tip I like – make a Worry Jar and write down your worry, stick it in the jar, schedule 15 minutes to go through your Worry Jar once a week. Saves mental strain to not have an overload on your mind. Writing lists or goals can help put them someplace else where you know you can find it again, and have a little more peace of mind.

Great design should be ‘intuitive.’ Translation: feel natural.
— Tom Peters

Nature repeats chemical structures and pathways across the chain of life. The essential omega 3 fatty acid DHA is ancient, unchanged from simple life forms to complex.

This post is the first of a series, in which I will share my Genes Table.

It has the solution for the health problems that gene alleles may cause – plant polyphenols. Polyphenols may be able to correct the up or down regulation in important pathways that the dysfunctional allele caused by affecting microRNA.

  1. microRNA are the real regulators of gene transcription.Substack.
  2. microRNA, elevated homocysteine and is there a role for excess Retinoic Acid?” ( *The hyperhomocysteinemia/homocystinuria section of my Genes Table.
  3. Pollutants in Human Plasma Found via Double-Filtration Plasmapheresis Plasma Exchange”, James Lyons-Weiler. ( *This is a cross post. Heavy metal toxins and thread like objects and aluminum-silicon combinations were found in a filtration of plasma procedure. This is related to pomegranate because the peel is effective at clumping nanoparticles into larger clumps that are big enough for white blood cells to sense as something needing to be removed.
  4. POTS – Postural Orthostatic Tachycardia Syndrome, can be epigenetic & therefore may be reversible”. ( *The Dystonia section of my Genes Table.

Before moving on to more sections, or exploring other conditions and yet more links…

This one is excellent and has a video abstract/overview: (Hayden, Tyagi, 2022) Hayden, M.R., Tyagi, S.C., (2022). Impaired Folate-Mediated One-Carbon Metabolism in Type 2 Diabetes, Late-Onset Alzheimer’s Disease and Long COVID. Medicina. 58(1):16. Available at (Accessed: 4 Dec 2022) Figure 1: Folate-Mediated One-Carbon Metabolism (FOCM).

In it we learn that the one-carbon methylation cycles are used within cell’s cytoplasm, within the mitochondria, and within the cell’s nucleus – and if the nucleus version is impaired, then … methylation of DNA will be impaired – it will not occur. Epigenetic changes will be very likely if there is dysfunction in the one-carbon methylation cycle within the nucleus.

Nature loves a good design and will repeat it.

Figure 2. Compartmentalization of FOCM. Note the presence of the folate-methionine one carbon cycle metabolism in the cytoplasm (cytosol), mitochondria and nucleus. Additionally, note the importance of formate being transferred from the mitochondria to the nucleus, as well as S-adenosylmethionine (SAM) via nuclear pores. Importantly, deoxythymidine monophosphate (dTMP) synthesis occurs in the cytosol, nucleus and mitochondria, whereas purine synthesis and methionine synthesis take place within the cytosol. Mitochondrial FOCM generates formate for cytosolic and nuclear FOCM and biosynthetic precursors for mtDNA synthesis and mitochondrial protein translation. Thymidylate synthase (TYMS) converts deoxyuridine monophosphate (dUMP) to dTMP in a 5,10-methylene-THF-dependent reaction (not shown). It is important to note that mitochondrial SAM (Mt SAM) is derived from cytosolic SAM (cSAM). Additionally, the Krebs cycle also resides within the mitochondria and provides NADH and FADH2 to the electron transport chain for ATP production. ATP = adenosine triphosphate; c = cytosol; ETC = electron transport chain; FAD = flavin adenine dinucleotide; FADH = reduced flavin adenine dinucleotide; FFA = free fatty acids; HHcy = hyperhomocysteinemia; MS = methionine synthase; Mt = mitochondria; NADH = reduced nicotinamide adenine dinucleotide; T = thymidylate-thymine; U = uracil.” (Hayden, Tyagi, 2022)

I had a reply recently saying nobody understands this (roughly) and my response would be: We learn by studying things that we don’t understand and looking up whatever words we need to look up in order to better understand it.

Here, in this complex graphic (above) – even a First Grader might guess that “Formate” is important. It appears that the nucleus version of the one-carbon cycles will not occur without formate to get it started. SAM is also important – the one-carbon cycle taking place in the cell’s cytoplasm creates the methyl donor cSAM which is converted into mitochondrial mSAM. The nucleus needs the (I don’t know what it is either) “Formate” and cSAM to enter through nuclear pores in order for the one-carbon cycle to be able to take place within the nucleus for DNA methylation needs. Meaning mitochondrial dysfunction of the one-carbon cycle leads to epigenetic changes and lack of DNA methylation in the nucleus of the cell, and dysfunction of the one-carbon cycle in the cytoplasm might precede the mitochondrial dysfunction as the cSAM is needed by the mitochondria and the nucleus. (Hayden, Tyagi, 2022) *They recommend that physicians screen homocysteine levels more often – it is not standardly measured with basic labs.

Formate, heat stress and SMYD3.

Internet answers: Formate is a result of the breakdown of Carbon dioxide, CO2,— and various engineering research approaches have been used to try to reduce CO2 from the air by promoting formate production (in microbes or chemical reactions) – but that is tangentially related and simply was the immediate search results. More to the physiological point – if we want to be able to make formate, we need the gene SMYD3 to be functional and active as it promotes synthesis of formate.

Conclusions: Our study demonstrates that SMYD3 regulates the activity of the mitochondrial metabolic enzyme MTHFD1L through H3K4me3 histone methylation modification, promotes formate synthesis and induces mitophagy, which inhibits M1 polarization in macrophages.” (Zhu, et al., 2022)

SMYD3 is important in histone methylation, and growth of embryos and cancer tumors, in order to localize it to the nucleus, where we need it for the one carbon cycle and methylation of DNA, Heat Shock Protein 90 (HSP 90) is needed as a nuclear chaperone (~transport protein). “[12, 23, 31]” (Bernard, et al, 2021)

In summary, SMYD3 is critical for the activation of MAP3K2, a key kinase in the Ras-activated MAP signaling pathway, in both lung and pancreatic cancers. Furthermore, SMYD3 is associated with advanced stage and poor survival in NSCLC, and promotes cell proliferation, invasion, and chemotherapy resistance phenotypes.” (Bernard, et al, 2021)

… ‘miR-3613-3p/MAP3K2/p38/caspase-3 pathway regulates the heat-stress-induced apoptosis of endothelial cells’ (Liu, Liu, Chen, 2021)

The results revealed that miR-3613-3p expression was reduced in human umbilical vein endothelial cells (HUVECs) following [heat stress] HS, which led to apoptosis. Mechanistically, following HS, a decrease in miR-3613-3p binding to the 3′-untranslated region of MAP3K2 directly upregulated its expression, and the downstream p38 and caspase-3 pathways, thereby leading to apoptosis. Taken together, the results of the present study demonstrated that HS suppressed miR-3613-3p expression, which activated the MAP3K2/p38/caspase-3 pathway, leading to the apoptosis of HUVECs.” (Liu, Liu, Chen, 2021)

Our goal – to not get overheated – avoid heat stress.

Not the same miRNA exactly, but from an interesting paper. “Chen et al. identified two miRNAs (hsa-miR-1307-3p and hsa-miR-3613-5p) that could prevent viral replication by targeting the 3′-UTRs of replication-related SARS-CoV-2 RNA 67.” (Yang, et al., 2022)

Pomegranate and heat stress – nature designed the plant to tolerate heat.

Pomegranate is a sustainable crop because it can tolerate heat, and salty soil and doesn’t need much water. The MAPK pathway is inhibited by pomegranate peel extract, and also by the 9 polyphenols discussed in the post: 1. “microRNA are the real regulators of gene transcription.Substack. I am not sure if the MAP3K2 is similarly inhibited but it seems likely.

Postural Orthostatic Tachycardia Syndrome can have an epigenetic cause.

Why is this important? Postural Orthostatic Tachycardia Syndrome is no fun and kind of scary. If you stand up too fast, your blood pressure can no longer shift quickly enough, however that works, and you get dizzy and need to grab something and rest a minute to get the accompanying tachycardia (very rapid heart rate, like it is trying to leap out of your chest almost). Laying down and lifting the knees and feet up helps slow the heart rate. Sitting or at least pausing is necessary or fainting may occur. I did faint once or twice and that is an odd feeling to find yourself on the floor after you come around. See: POTS – Postural Orthostatic Tachycardia Syndrome, can be epigenetic & therefore may be reversible. ( *Includes the Dystonia section of my Genes Table with more info and a link to my book chapter on the topic (but in computer lingo, the links don’t work).

Many chronic conditions involve epigenetic changes. Sometimes it can be reversed but not always and less likely the longer the condition has lasted. I had POTS-like symptoms for a few months twice and I figured out how to get better. It is not a fun condition and standard treatment usually does not help enough. People become physically disabled as it worsens. You can’t over-exert or stand up too fast or the symptoms of dizziness and racing heart occur.

When you have an open mind, you can learn new things.

Epigenetics – the basics.

Epigenetics – an overview/the opening of an Abstract about a review paper focused on cancer treatment and epigenetics:

Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression.

In mammals, epigenetic mechanisms include changes in

  • DNA methylation,
  • histone modifications and
  • non-coding RNAs.
    • [microRNA are non-coding RNAs (19-23 nucleotides) and there are also longer ones (up to ~100, or a few >/= 200 nucleotides) that are still shorter than an mRNA which is used to transcribe a protein, so it is the full length of the matching DNA from the gene sequence, but only half of the zipper/ladder shape of the double helix.]

Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies. Burgeoning evidence in the last decade has provided unprecedented clues that diet and environmental factors directly influence epigenetic mechanisms in humans. Dietary polyphenols from green tea, turmeric, soybeans, broccoli and others have shown to possess multiple cell-regulatory activities within cancer cells. More recently, we have begun to understand that some of the dietary polyphenols may exert their chemopreventive effects in part by modulating various components of the epigenetic machinery in humans.” (Link, Balaguer, Goel, 2010)

*Bullet points and note added by me. See: Non-coding RNAs: Classification, Biology and Functioning. (Hombach, Kretz, 2010)

Cancer is mitochondrial dysfunction related to cytoplasm dysfunction of the One-Carbon Methylation cycles.

As it turns out, nature really likes the one-carbon methylation cycle and mitochondria seem to be a control center of our cells rather than the nucleus. Cancer is dysfunction of mitochondria which leads to aberrant signaling to the cell nucleus which leads to cancerous like changes in their growth. Experiments have shown though, that when the nucleus of a cancer cell, with the gene changes in place, is transplanted into a healthy cell with healthy mitochondria and cytoplasm, the cell does not become cancerous. However, when a nucleus from a healthy cell is transplanted into a cancer cell that had its nucleus removed, the cell remains cancerous. When cancer cell mitochondria are transplanted into a healthy cell with a normal nucleus – it changes into a cancer cell with cancerous gene changes and out of control growth. The increased growth may be part of more normal pathways used during embryology and child growth. This indicates that cancer is NOT a GENETIC disease. The disease pathology was connected to the diseased cell’s mitochondria, not the diseased cell’s nucleus.

It turns out that mitochondria direct events within the cell and are the controller for signaling the need for apoptosis – put this cell to a merciful death, it is done. But with dysfunctional mitochondria there is no signal presented to kill the cell and it grows out of control or remains dysfunctional but alive – a senescent cell – alive and consuming, but no longer producing functional benefits for the organism or organ.

Cancer is a mitochondrial dysfunction. The one flaw in Dr Seyfried’s treatment plan though, is that such a high fat diet will still promote mitochondrial dysfunction. I would recommend a less stringent ketone diet, at least after some short-term initial phase that is moderate carb and >/= 50% of calories from fats. Use more ketones and some protein, but a diet above 60% fat may in itself cause mitochondrial dysfunction.

His depressing but helpful message is that also, the chemotherapy, radiation and some of surgical approaches are likely just adding to mitochondrial dysfunction and making the cancer worse. Carbohydrates and glutamates need to be restricted – and that equals sugar, bread, potatoes, pasta, pizza, tomato products, cheese, soy sauce, Worcestershire sauce, barbecue sauce or barbecue, artificial seasonings, ice cream, sweetened beverages, etc – much of the modern diet in other words.


/Housekeeping – I noticed an older comment suggesting that I provide checklists or more guidance for what to do, regarding my Table 5 – Nutrients depleted by psychiatric medications, which also are nutrients needed by mitochondria, and are risk factors for schizophrenia, Alzheimer’s dementia, or COVID19. I shortened the name of that Table to ‘Nutrients of Concern’.


  • Downloadable Tools in my toolbox – by Jennifer Depew, R.D. (
  • My first Substack post is still pertinent – Nrf2 & NF-kB – 2 proteins to know. (

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

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(Hayden, Tyagi, 2022) Hayden, M.R., Tyagi, S.C., (2022). Impaired Folate-Mediated One-Carbon Metabolism in Type 2 Diabetes, Late-Onset Alzheimer’s Disease and Long COVID. Medicina. 58(1):16. Available at (Accessed: 4 Dec 2022) Figure 1: Folate-Mediated One-Carbon Metabolism (FOCM), Figure 2. Compartmentalization of FOCM.

(Hombach, Kretz, 2010) Hombach S, Kretz M. (2016). Non-coding RNAs: Classification, Biology and Functioning. Adv Exp Med Biol. 937:3-17. doi: 10.1007/978-3-319-42059-2_1. PMID: 27573892. Available at: (Accessed: 5 Dec 2022)

(Link, Balaguer, Goel, 2010) Link, A., Balaguer, F., Goel, A., (2010). Cancer Chemoprevention by Dietary Polyphenols: Promising Role for Epigenetics. Biochemical pharmacology. 80:1771-92. 10.1016/j.bcp.2010.06.036. Available at: 5 Dec 2022)

(Liu, Liu, Chen, 2021) Liu J, Xu S, Liu S, Chen B. (2021). miR‑3613‑3p/MAP3K2/p38/caspase‑3 pathway regulates the heat‑stress‑induced apoptosis of endothelial cells. Mol Med Rep. Sep;24(3):633. doi: 10.3892/mmr.2021.12272. Epub 2021 Jul 19. PMID: 34278472; PMCID: PMC8280962. Available at: (Accessed: 5 Dec 2022)

(Yang, et al., 2022) Yang, C.Y., Chen, Y.H., Liu, P.J., Hu, W.C., Lu, K.C., Tsai, K.W., (2022). The emerging role of miRNAs in the pathogenesis of COVID-19: Protective effects of nutraceutical polyphenolic compounds against SARS-CoV-2 infection. Int J Med Sci. Jul 18;19(8):1340-1356. doi: 10.7150/ijms.76168. PMID: 35928726; PMCID: PMC9346380. Available at: (Accessed: 5 Dec 2022)

(Zhu, et al., 2022) Zhu, W., Wang, S., Xue, L., Liu, L., Yang, X., Liu, Z., et al., (2022). The SMYD3-MTHFD1L-formate metabolic regulatory axis mediates mitophagy to inhibit M1 polarization in macrophages, International Immunopharmacology, 113(Part A), 2022, 109352, ISSN 1567-5769,