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 workflowy.com (https://workflowy.com/s/hyperinflammation-pr/NA9NrJpva8lyi1nH) 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 peace-is-happy.org, 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. (peace-is-happy.org) 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?” (substack.com) *The hyperhomocysteinemia/homocystinuria section of my Genes Table.
  3. Pollutants in Human Plasma Found via Double-Filtration Plasmapheresis Plasma Exchange”, James Lyons-Weiler. (substack.com) *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”. (substack.com) *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. https://doi.org/10.3390/medicina58010016 Available at https://www.mdpi.com/1648-9144/58/1/16 (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. (substack.com) *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.

https://www.youtube-nocookie.com/embed/KusaU2taxow?rel=0&autoplay=0&showinfo=0&enablejsapi=0

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.

Resources

/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’.

See:

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

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

(Bernard, et al, 2021) Bernard, B.J., Nigam, N., Burkitt, K. et al., (2021). SMYD3: a regulator of epigenetic and signaling pathways in cancer. Clin Epigenet 13(45) https://doi.org/10.1186/s13148-021-01021-9 Available at: https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-021-01021-9 (Accessed: 5 Dec 2022)

(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. https://doi.org/10.3390/medicina58010016 Available at https://www.mdpi.com/1648-9144/58/1/16 (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: https://pubmed.ncbi.nlm.nih.gov/27573892/ (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: https://www.researchgate.net/publication/45090894_Cancer_Chemoprevention_by_Dietary_Polyphenols_Promising_Role_for_Epigenetics/citation/download(Accessed: 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: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280962/ (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: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346380/ (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, https://doi.org/10.1016/j.intimp.2022.109352. https://www.sciencedirect.com/science/article/pii/S1567576922008360

Niacin, & early treatment in general for SARS-CoV-2 is sensible, reduces hospitalization and mortality rate.

The longer a viral infection is allowed to progress the more cells are killed or damaged, either by the viral replication, or by the damaged cells contents harming the surrounding tissue . See for more information: Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. (1)

*post updated 8/1/2021, & 8/24/2021, & 9/2/2021.

See my recent post for a variety of nutrients or other strategies which may help prevent or provide early treatment for a viral infection: COVID19, summary of nutrients that might help prevent, treat, recover. Or more recent: Spike Protein Risks & Aids – summary list.

The post Niacin may help prevent or treat migraines also includes a graphic by Dmitry Katz, PhD about the cofactors used in the Citric Acid Cycle by mitochondria when they are performing aerobic glycolysis – metabolizing sugar with the use of oxygen. Mitochondrial dysfunction and a shift to anaerobic metabolism of sugar or glutamate, fermentation, is associated with cancer cells and other chronic degenerative disease. The cause may be limited nutrients – the list of cofactors needed is long and includes niacin.

Cofactors needed in the Citric Acid Cycle include niacin:

  • B vitamins: B1 (Thiamin) (3) , B2 (Riboflavin) (4), B3 (Niacin) (810), B5 (Pantothenic acid) (5), B6 (Pyridoxine) (67), B7 (Biotin), B9 (Folate) (9),
  • Minerals (17): Mg++ (Magnesium) (111213), Mn++ (Manganese), K+ (Potassium) (13), Zinc (1415), Iron (16), Copper, Sulfate,
  • Amino acids: Carnitine (derived from lysine), Cysteine,
  • Antioxidants: CoQ10, Glutathione, Alpha-Lipoic Acid (ALA).

Niacin in a large dose may help with treatment of an active COVID19 illness or the symptoms of LongCovid. Specifically the niacin/nicotinic acid form, not niacinamide. The “niacin flush” that occurs is warm – and is removing inflammation along with the increased sensation of warmth on the skin. Feeling a little chilled as the niacin flush continues is also normal, internally the body is cooling somewhat as the inflammation is being removed as heat on the skin.

This article summarizes the value of a variety of B vitamins against viral infections and/or inflammation and goes into more detail about niacin use for prevention or treatment of infections and inflammation: Is Niacin a Missing Piece of the COVID Puzzle?. (2) Niacin helps our body cope with increased inflammation and without niacin the inflammation continues to become more severe. For more detail see: Sufficient niacin supply: the missing puzzle piece to COVID-19, and beyond? by Dmitry Kats, PhD (3); and Be Well: A Potential Role for Vitamin B in COVID-19, a team project including scientists from several nations. (4)

Niacin (nicotinic acid) Protocol against COVID-19,
shared with permission of the author, Dmitry Kats, PhD. *His website: niacincurescovid.com.
*The apples and antihistamines can decrease the flush effect if it seems like too much and should be fine at other times of the day, than taken with or shortly after the niacin dose.

Adequate niacin may also help the body have a stable thyroid hormone level. (5)

Low levels of niacin and a metabolite NAD+ may be involved in mitochondrial myopathy which leads to tiredness and weak muscles. Providing 500-1000 milligrams of niacin per day was found to improve muscle strength, increase NAD+ levels to the level seen in the healthy control group, and liver fat decreased by 50% in the experimental group. (6)

Potential short term symptoms – may include serotonin increase.

People who were previously low in serotonin, a neurotransmitter that affects mood and intestinal health, may experience temporary symptoms from an increase in the messenger chemical. Once the body adjusts to the new level of serotonin the symptoms should no longer occur. Symptoms of a sudden increase, or excess of serotonin may include: Agitation or restlessness, Confusion, Rapid heart rate and high blood pressure, Dilated pupils, Loss of muscle coordination or twitching muscles, Muscle rigidity, Heavy sweating, Diarrhea, Headache, Shivering, Goose bumps. (13) People experiencing Serotonin Syndrome for other reasons would likely have more severe symptoms than the short term change due to the increase in niacin. Tryptophan is an amino acid precursor for serotonin and it is depleted when there is inadequate niacin available to make NAD+.

Addition 8/1/21: St. John’s Wort herbal supplements, 5-HTP, and other medications including SSRI antidepressants may increase risk of serotonin toxicity. The problem usually is seen with SSRI use, and treatment generally is to wean off the amount of whatever is being taken, without a sudden stop in case of adverse reaction to that, and the symptoms should lessen. See: St. John’s Wort Drug Interactions with Antidepressants (17)

During acute infection the risk of serotonin toxicity becoming severe is more of a concern to medical professionals I’ve been in communication with. The gradual increase over time may help when it is being used preventatively. Caution is advised with high dose niacin use. Serotonin inhibitor treatment would be needed if the problem of serotonin excess was severe.

Addition 8/24/2021: The FLCCC protocol for CoV may include SSRI medications and trying the niacin protocol and the I-MASK+ FLCCC protocol in combination may increase risk of the serotonin excess. Sudden increase of the niacin dosing to the 1000 mg amounts may also increase the risk of the adverse symptoms of serotonin excess. Try to remain calm, it is temporary though can be dangerous. Seek medical help and cut back on the niacin or SSRIs but suddenly stopping may also be risky. The FLCCC protocol uses fluvoxamine an SSRI.

Saffron taken as a medicinal herbal supplement (88 mg day per Dr. Grouf) may also help by preventing a serotonin excess which may also be a risk of a severe infection condition. “Saffron will restore breathing, heart rate and clear the lungs, it will also prevent serotonin induced injury to brain, lungs and heart and fix co–d diarrhoea” (@DGrouf)

Saffron extract may inhibit serotonin reuptake in synapses (Sophia Esalatmanesh et al., 2017). Serotonergic mechanisms have been influenced by crocin by showing antagonistic action at the 5-HT2c receptor site (Lopresti et al., 2014).
Saffron: The Age-Old Panacea in a New Light, by Maryam Sarwat · 2020, page 125, Chapter 10: Saffron in Brain Diseases, (Google Books) via (@DGrouf)

Another caution against taking saffron at the same time as curcumin/turmeric, as the phytonutrients have opposing mechanisms of action. https://twitter.com/MirrorManDan/status/1430203127257608192?s=19

Dizziness – niacin, nicotinamide and nicotine in combination, can have an adverse effect.

Dizziness may result from a combination of niacin, nicotinamide, and use of a nicotine patch. Niacin/(rxlist.18) Solution – stop taking the niacinamide.

Niacin is converted into niacinamide during metabolic use of the nutrient, so taking both is not really necessary.

Chemically, niacin is one of the simplest vitamins, having the empirical formula C6H3O2N (Illus. 13-1). Nicotinic acid and nicotinamide correspond to 3-pyridine carboxylic acid and its amide, respectively.” […] “Nicotinic acid is converted to the amide form in the tissues, and Erickson et al. (1991) suggests this occurs in the rumen. [article about supplements for lactating cows > is helpful] Nicotinamide functions as a component of two coenzymes: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).” […] (16)

Although niacin coenzymes are widely distributed in the body, no true storage occurs. The liver is the site of greatest niacin concentration in the body, but the amount stored is minimal.” […] (16)

Niacin can be made from tryptophan, an amino acid, as long as there is also adequate protein, energy, vitamin B6, riboflavin and necessary hormones available. Iron is also needed. Synthesis may take place in the gut as well as throughout the body. See longer excerpt in the Reference List. (16)

Glyphosate may be reducing average tryptophan levels in our diet, and in our bodies.

Glyphosate residue in our food supply may be reducing our levels of tryptophan and other amino acids (14) and trace minerals such as manganese. (15) Glyphosate is a mineral chelator and antibiotic affecting a chemical pathway that affects tryptophan. That may disrupt bacterial health, and was thought to not risk human health too, however it may affect us due to our need for the amino acids., in addition to other effects that have been less studied then the shikimate pathway mechanism of action.

The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan.” (Vivankos et al., 2011) (14)

Potential long term risks – may affect liver health and gout – uric acid; quercetin may help reduce risk of uric acid build up.

People with liver damage or gout may need to avoid taking large doses of niacin long term (more than 2000-6000 mg/day). Taking it along with alcohol use may increase the risk of liver damage and worsen the symptoms of the niacin flush with itching. Long term use of large doses may lead to gout, excess uric acid. (7) Symptoms of gout can occur abruptly even waking up at night with severe joint pain, most frequently occurring in the joint at the base of the large toes. Other joint tissue can also be affected. Pain, swelling and redness in the affected toe or other joints are typical symptoms. (8)

Use of large doses of niacin/nicotinic acid for treatment of patients with symptoms of schizophrenia were studied extensively in the 1950s-70s. Use of nicotinamide was not found to help similarly and the treatment was most immediately beneficial for patients with acute onset of the schizophrenia symptoms. People with chronic schizophrenia took longer to respond to use of niacin and needed larger doses to achieve symptom relief. Regarding risk of toxicity, liver concerns, gout, and increases in blood uric acid were observed but were not too severe of a problem, compared to the adverse side effects seen with standard psychiatric medications, and some patients could use a different form or a smaller dose. “The vitamin has been given to patients suffering from gout whose symptoms were not aggravated and it did not interfere with their specific treatment for gout.” (9)

Uric acid/urate levels in gout can be reduces with use of xanthine oxidase inhibitors (10) which include the phytonutrient quercetin. (11) For more information about quercetin’s other benefits as a zinc ionophore and bioflavonoid see the recent post: COVID19, summary of nutrients that might help prevent, treat, recover.

Quercetin is found in many plant foods in small amounts, and rich in some foods like capers (Alcaparras) and cilantro. It is also found in citrus and pomegranate peel. “The researchers note that pickling promotes conversion of rutin (flavonoid compound also called rutoside in capers) to quercetin, the ingredient that they found to be an efficacious KCNQ channel activator. This makes pickled capers as the richest known “natural” source of quercetin, with a maximum reported concentration of 520 mg/100 g for canned capers, compared to a maximum of 323 mg/100 g quercetin for raw capers.” (12) People with Mast Cell overactivity (seasonal allergy & other symptoms might be present) may need to avoid pickled or other fermented foods as that can worsen mast cell symptoms, for more information see: MCAS/Histamine.

Other nutrients that may help as cofactors recommended by Dimitry Kat’s, Ph.D. include vitamin C, a B complex, vitamin D3, zinc, magnesium, and Black seed oil, quercetin, and N-acetyl cysteine could provide additional antioxidant support.

Dr. Kats’ All Natural Daily Protocol for COVID19 (*may help preventively, during viral or other infections, and during recovery. The nutrients help the body remove inflammation as heat loss, the skin reddening ‘niacin flush’. The nutrients also are used by mitochondria to provide us energy and reduce risk of cancer. Niacin and magnesium help cells engulf damaged cells, pathogens, and chemical debris, or tangled proteins for reuse as nutrients. )

Dr. Kats’ Niatonin Protocol (update 9/2/21)

Melatonin and niacin are recommended in the most recent version of the Kats’ protocol, available in this post: Spike summary spreadsheet; telomerase, Circadian cycle & Nrf2, Aug. 22, 2021. Caution: Melatonin is a hormone normally present and active in very tiny amounts, not a milligram, micrograms, and too much may disrupt sleep cycle. Too much regularly, may suppress our own production of melatonin.

Simply focusing on improving sleep habits and getting full spectrum light during the day can help all of the genes and hormones effected by our circadian cycle. Hundreds of genes are activated or de-activated during the day/night transitions – during normal health. Modern life tends to keep us in the inflammatory day time mode – all of the time. That is really what Metabolic Syndrome is – constant low level inflammation instead of cycling between anti-inflammatory night-time growth and repair mode, and the active get busy and do stuff, inflammatory day-time mode.

Disclaimer: This 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. Peter A. McCullough, MD, MPH. et al., Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. August 06, 2020 American Journal of Medicine, VOL 134, ISSUE 1, P16-22, JANUARY 01, 2021 DOI:https://doi.org/10.1016/j.amjmed.2020.07.003 https://www.amjmed.com/article/S0002-9343(20)30673-2/fulltext
  2. Mercol J, Is Niacin a Missing Piece of the COVID Puzzle?, Jan 20, 2021, mercola.com, https://articles.mercola.com/sites/articles/archive/2021/01/20/what-are-the-benefits-of-niacin.aspx
  3. Kats D, Sufficient niacin supply: the missing puzzle piece to COVID-19, and beyond?, preprint, https://osf.io/uec3r/
  4. Be Well: A Potential Role for Vitamin B in COVID-19, Maturitas, Shakoor H, Feehan J, Mikkelsen K, et al. Be well: A potential role for vitamin B in COVID-19. Maturitas. 2021;144:108-111. doi:10.1016/j.maturitas.2020.08.007 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428453/
  5. Shakir KM, Kroll S, Aprill BS, Drake AJ 3rd, Eisold JF. Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state. Mayo Clin Proc. 1995 Jun;70(6):556-8. doi: 10.4065/70.6.556. PMID: 7776715. https://pubmed.ncbi.nlm.nih.gov/7776715/
  6. Pirinen E, Auranen M, Khan NA, Brilhante V, Urho N, Pessia A, Hakkarainen A, Kuula J, Heinonen U, Schmidt MS, Haimilahti K, Piirilä P, Lundbom N, Taskinen MR, Brenner C, Velagapudi V, Pietiläinen KH, Suomalainen A. Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metab. 2020 Jun 2;31(6):1078-1090.e5. doi: 10.1016/j.cmet.2020.04.008. Epub 2020 May 7. Erratum in: Cell Metab. 2020 Jul 7;32(1):144. PMID: 32386566. https://pubmed.ncbi.nlm.nih.gov/32386566/
  7. Niacin, mayoclinic.org, https://www.mayoclinic.org/drugs-supplements-niacin/art-20364984
  8. Gout – Symptoms & Causes, mayoclinic.org, https://www.mayoclinic.org/diseases-conditions/gout/symptoms-causes/syc-20372897
  9. Hoffer A, Megavitamin B-3 Therapy for Schizophrenia, Canad. Psychiat. Ass. J. Vol. 16 (1971) https://journals.sagepub.com/doi/pdf/10.1177/070674377101600605
  10. White WB, Gout, Xanthine Oxidase Inhibition, and Cardiovascular Outcomes. Circulation. 2018;138:1127–1129 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.036148
  11. Zhang C, Wang R, Zhang G, Gong D. Mechanistic insights into the inhibition of quercetin on xanthine oxidase. Int J Biol Macromol. 2018 Jun;112:405-412. doi: 10.1016/j.ijbiomac.2018.01.190. Epub 2018 Jan 31. PMID: 29410028. https://pubmed.ncbi.nlm.nih.gov/29410028/
  12. Kim Stewart, Discovery: Caper Berry’s Quercetin Activates KCNQ Potassium Channel. July 16, 2020, todayspractitioner.com https://todayspractitioner.com/botanical-medicine/discovery-caper-berrys-quercetin-activates-kcnq-potassium-channel/
  13. Serotonin Syndrome: Symptoms & Causes, mayoclinic.org https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758
  14. Vivancos PD, Driscoll SP, Bulman CA, et al. Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration. Plant Physiol. 2011;157(1):256-268. doi:10.1104/pp.111.181024 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165874/
  15. Samsel A, Seneff S. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies. Surg Neurol Int. 2015;6:45. Published 2015 Mar 24. doi:10.4103/2152-7806.153876 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392553/
  16. Niacin, DSM.com, https://www.dsm.com/anh/en_US/products/vitamins/vitamin-nutrition-compendium/companion-animals/niacin.htmlThe amino acid tryptophan is a precursor for the synthesis of niacin in the body. There is considerable evidence that synthesis can occur in the intestine. There is also evidence that synthesis can take place elsewhere within the body. The extent to which the metabolic requirement for niacin can be met from tryptophan will depend first on the amount of tryptophan in the diet and second on the efficiency of conversion of tryptophan to niacin. The pathway of tryptophan conversion to nicotinic acid mononucleotide in the body is shown in Figure 13-1. Protein, energy, vitamin B6 and riboflavin nutritional status as well as hormones, affect one or more steps in the conversion sequence shown in Figure 13-1. Therefore, they can influence the yield of niacin from tryptophan. Iron is required by two enzymes for the conversion of tryptophan to niacin with a deficiency reducing tryptophan utilization.” (16)
  17. St. John’s Wort Drug Interactions with Antidepressants, verywellmind.com, https://www.verywellmind.com/st-johns-wort-drug-interactions-with-antidepressants-1066686
  18. Niacin, RxList.com https://www.rxlist.com/niacin/supplements.htm

Fonia- sustainable grain

Our changing world and growing population can benefit from changing what we put on our menu plans – change what we eat often. Fonia is a drought tolerant grain in the millet family which can be harvested in just six to eight weeks from planting and it tolerates poor soil conditions.

Fonia is native to West African countries and may also have been used by ancient Egyptian cultures as the grain has been found in archeological sites.

Fonia is cooked similarly to rice but is a smaller grain. It would be good as a hot breakfast porridge or used like rice in salads or side dishes. It is gluten free, rich in fiber, protein, magnesium, zinc, and B vitamins. For more information and a couple recipes see: “Whole Grains- Fonio,” By Jessica Levinson, Today’s Dietitian, https://www.todaysdietitian.com/newarchives/0918p12.shtml

Disclaimer: Information provided for educational purposes within the guidelines of fair use, not intended for individual health care guidance.

Choline and betaine – water soluble nutrients

Choline is a newer discovery in the nutrient world. It is considered to be a member of the water soluble B vitamins group which are nutrients involved in metabolism – the use of energy within the body. We can produce small amounts of choline so it isn’t considered a vitamin but as we can not produce enough for health it is considered an essential nutrient. (1) Betaine is a slightly different form of choline. Choline is found throughout the body but is particularly important within the brain and is needed for the neurotransmitter acetylcholine. Betaine is a metabolite of choline.

Choline, a water soluble nutrient. Foods Sources and symptoms of deficiency.

Choline is most typically found within phospholipids (such as phosphatidylcholine) which are important in membranes and as messenger chemicals within the brain and in the immune system. It may play a role in prenatal brain development but research on supplementation within pregnancy r to protect cognitive skills in the elderly is still in early stages. (1)

Choline is a  methyl donor (1) which means it can share a methyl group – essentially one carbon atom with three hydrogen atoms with an overall neutral charge.

An important role of methyl groups is in the release of energy from sugar within mitochondria. The methyl group is passed back and forth between nutrients and enzymes that are involved in breaking down a molecule of fat or sugar for use of the stored energy that is released when a double bond is broken. The methyl group is combined with an acetyl group when it is removed from the area on the chain of carbon molecules when a double bond is broken. An acetyl group is an atom of carbon combined with one atom of hydrogen and the group has a negative charge. The process for breaking down the glucose sugar molecule is called the Krebs cycle and most beginning level organic chemistry or nutrition students will remember having to memorize all of the steps involved. My summary may be inaccurate – college was a long time ago – the important point is that B vitamins and methyl donors are needed for mitochondria to be able to release energy from glucose/sugar molecules).

  • (The Krebs cycle is also known as the “citric acid cycle or the tricarboxylic acid (TCAcycle.” More info: Krebs cycle.)

Methyl groups are also important in controlling gene activity. They act like an on/off switch for genes. A gene that is fully methylated – all the available double bonds between carbon atoms are broken into single bonds with a methyl group added instead – is in the off position, the protein that the gene would encode is not being made. Genes that are unmethylated have double bonds and are in the on position, the pattern for assembling amino acids into a protein can be read by a matching strand of RNA and the protein can be formed (generally in the endoplasmic reticulum or Golgi apparatus areas of a cell).

Betaine and the more familiar B vitamins folate (B9 if anyone is counting), B6 and B12 are also methyl donors. Folate deficiency has been associated with less gene methylation (a histone is part of a gene). (2) More about methyl donors as a group is available here:  Methyl Donors and BPA.

  • The number system for naming B vitamins was derived at an earlier stage of research and some of the chemicals that were given numbers at the time were discovered to not be essential nutrients – meaning the body was able to form them within the normal health and didn’t essentially need to have them included in the diet (so that is why we don’t hear about a B4, B8, B10 or B11).

Excessive intake of choline above 7500 milligrams may cause a drop in blood pressure, sweating, vomiting and digestive upset, and change in body odor. The recommended Upper Limit is 3,500 mg/day. It would be difficult to reach that amount with food sources. (Safety information, lpi.oregonstate.edu)

Food Sources of Choline:

Good sources of choline include meats, fish & shellfish, eggs/egg yolks, cheese, milk, yogurt, broccoli, cauliflower, cabbage, kale, kohlrabi and other cruciferous vegetables, green leafy vegetables, pomegranate seeds, sesame seeds, tahini, peanuts,  soybeans, beans, brown rice, whole grains.

Food Sources of Betaine:

Sweet potatoes, meats, cheese, beets, basil, spinach, green leafy vegetables, brown rice, whole grains.

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.

References:

  1. Choline, Linus Pauling Institute, Oregon State University, http://lpi.oregonstate.edu/mic/other-nutrients/choline
  2. Benjamin A. Garcia, Zigmund Luka, Lioudmila V. Loukachevitch, Natarajan V. Bhanu, Conrad Wagner, Folate deficiency affects histone methylation,

    Medical Hypotheses, Volume 88, March 2016, Pages 63-67, ScienceDirect, https://www.sciencedirect.com/science/article/pii/S0306987716000116

  3. Foods used in the 30% Calories from Carbohydrates Menu Plans, https://effectiveselfcare.info/2018/05/19/healthy-hair-is-the-proof-of-a-healing-diet/