Category: B vitamins

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Aging biomarker found to be increased in LongCovid, epigenetic changes possible

Evidence of aging, five years on average, was found in survivors of Covid who experienced ongoing illness after an apparent recovery or even only ever having had mild symptoms initially. (1) Other research has found evidence of autoimmune antibodies against certain types of G-protein coupled receptors – need a different post for that.

  • Evidence for Biological Age Acceleration and Telomere 2 Shortening in Covid-19 Survivors. Alessia Mongelli, Carlo Gaetano, Michela Gottardi Zamperla, et al., medRxiv, April 27, 2021, preprint, (1)
  • “The results show a consistent biological age increase in the post-covid population (mean 58,44 DS 14,66 ChronoAge Vs. mean 67,18 DS 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 DS 7,29 years (+5.25 years above range of normality) compared to 3,68 DS 8,17 years for the COVID19-free population (P<0,0001). A significant telomere shortening parallels this finding in the post-COVID19 cohort compared to COVID19-free subjects (post-COVID19 TL: 3,03 DS 2,39 Kb vs. COVID19-free: 10,67 DS 11,69 Kb; P<0,0001).” (1)
  • Additionally, ACE2 expression was decreased in post-COVID19 patients compare to COVID19-free, while DPP-4 did not change. ” (1)

ACE2 receptor expression was expected to be decreased in patients with increased viral load due to the virus destroying the cells with the receptors. Eventually less ACE2 function would be left and patients would exhibit symptoms similar to genetic ACE2 knockout mice – bred to not have ACE 2 receptors in order to see the effect on health. It can provide information about what function something has to see what goes wrong when the animal doesn’t have it.

Also of interest – stopping the virus from entering the ACE2 receptor means that it can’t replicate and go on to infect other cells or people – pomegranate peel may block access: Pomegranate peel – anti-COVID19, may block ACE2 receptor access to the SARS-CoV-2 virus. I ate some pomegranate peel today. *Recipe at the end of this post, more information about pomegranate prep & benefits G13. Pomegranate.

Pomegranate extract reduces inflammation and modulates health and gene transcription.

Pomegranate extract, of the whole fruit or peel is a very potent anti-inflammatory and modulator of health, (6), even epigenetics to some extent – epigenetics effects which genes will be transcribed into proteins by the cell. Pomegranate extract was found to modulate/effect microRNAs which control which mRNA will get transcribed. (2)

“Pomegranate extract intake reversed the surgery-mediated upregulation of various miRNAs and mildly reduced expression of selected miRNAs in tumour tissue compared with normal tissue.” (2)

What is microRNA? — “Noncoding (nc) RNAs also possess a regulatory effect on gene expression. MicroRNAs (miRNAs) are small ncRNAs of 20–22 nt that inhibit gene expression at the posttranscriptional level either by imperfect base-pairing to the mRNA 3′-untranslated regions to repress protein synthesis, or by affecting mRNA stability (reviewed in [23]).” (2)

What is mRNA? — “Messenger RNA (mRNA) molecules carry the coding sequences for protein synthesis and are called transcripts;” (3) Messenger RNA is copied from the double helix strands of DNA that make a gene. The messenger RNA is a single helix – one ladder leg instead of both sides of the spiraling ladder with nucleotide steps, or one side of a zipper.

What is epigenetics? — “The term ‘epigenetics’ refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Major epigenetic mechanisms include DNA hyper- and hypomethylation [11], remodelling of the chromatin, modification of histones by histone acetylation and methylation (among others), and noncoding RNAs [12].” (2)

What are methyl donors? — Folate in the bioactive methylated form and methylated B12 are both helpful for providing the methyl groups needed for DNA methylation. The small chemical group added onto genes is like turning the light switch off, that gene is no longer in the ready to be transcribed mode. Choline is another methyl donor in the B vitamin group. See: Methyl Donors & BPA.

EGCG found in Green tea & Pomegranate Peel may protect length of Telomeres.

Pomegranate peel is also a source of EGCG (more commonly associated with green tea) which has been found protective of telomere length, by inhibiting a telomerase enzyme.

“Epigallocatechin-3-gallate, a major component of green tea polyphenols, downregulated expression of human telomerase reverse transcriptase (hTERT), a major enzyme determining telomere stability, through causing promoter hypomethylation and histone deacetylations, thereby inhibiting proliferation of breast cancer cells [12].” (7)

Polyphenols, alkaloids, triterpenes, and xanthones may be plant nutrients that help inhibit the overactivity of the telomerase enzyme seen in some types of cancer cells. (8) EGCG is a polyphenol. Alkaloids include “morphine, strychnine, atropine, colchicine, ephedrine, quinine, and nicotine.” (11) Triterpenes include sterols (such as vit. D group, 12) and carotenoids (vit A). (9) xanthones are found in the Garcinia, mangosteen fruit. (10) Telomeres are a section of non protein encoding DNA at the end of genes. Telomeres get shorter as we age and longer ones indicate younger metabolic age. Excessive lengthening of telomeres can occur in cancer and that isn’t good either.

The really good news about epigenetic changes – they can be changed back.

“In contrast to irreversible genetic alterations (mutations, deletions, etc.), genes silenced by epigenetic modifications are still intact and can be reactivated [13,14].” (2)

Many genes are turned on or off with the change from night to day/day to night. We do more active energy using work during the day, which produces waste chemicals, and more growth and repair, clean up, at night while we sleep. It is very unhealthy to chronically miss sleep.

Sunlight in the day & blackout curtains at night help immune function with melatonin & sunshine vitamins.

Sunlight in the morning or at some point in the awake hours of the day also helps health.

“People have a feeling of wellbeing when exposed to sunlight. This may be due to the fact that keratinocytes produce β-endorphin when exposed to UV radiation.67 ” (12)

A full spectrum lamp with UVB capability for a half hour of artificial “sun” during winter months or for night shift workers may be more beneficial for health, and mood, than a vitamin D2/D3 supplement. Our bodies make other forms of the vitamin D group of sterols, some water soluble, and other forms of vitamin A are also made. (12, 13)

“Bright light treatment requires a minimum of 2,500 lux to be effective, & the brightness recommended by researchers & clinicians for most people is 10,000 lux – an amount significantly higher than standard indoor lighting.” (14) This reference is recommending no UV in the light treatment, however for the vitamin D and A chemistry UVB is needed and UVA may also have some role in health in moderation.

Seasonal Affective Disorder (SAD) lamps may not provide the UVB, and the UVB intense ones are only meant for 30 minute use or less per day, as sunburn possible, so that type of light wouldn’t treat the SAD problem in the same way as the no UVB lights. (13, 15) The 10,000 lux lamps may be helping patients with Seasonal Affective Disorder (14) by increased beta-endorphins. Serotonin increase is involved in the benefit of Bright Light Therapy (BLT) which was found to be better than placebo in a metareview. (16) Bright Light Therapy was found to reduce cerebral monoamine oxidase A (MAO-A) levels which have a seasonal decrease in healthy controls compared to participants with SAD. Serotonin receptors and transport proteins may also be affected by the light treatment. (17)

Black out curtains at night and covering all little alarm clock lights and other device lights helps our body switch into night-time biology of clean-up and repair. Melatonin is also made at night and lights can reduce the amount that is made. It helps immune function and seems helpful against COVID-19. Melatonin produced in the lungs prevents infection by novel coronavirus. (18)

Lack of niacin, which is needed in increased amounts during infection or inflammation, would lead to overuse of tryptophan instead. Lack of tryptophan would lead to a lack of serotonin and melatonin, both of which are made from tryptophan. (19)

We may need a healthy gut microbiome, to have overall health.

The microbes in our intestines may have a larger role in health than we realized because they also impact our epigenetics – we want our good guys to be helping us then.

“Recent research has indicated that the gut microbiota and gut microbial metabolites might be important mediators of the diet–epigenome interaction (previously reviewed in [29–31]).” (2)

Obesity has been found to be related frequently to less beneficial microbiome species. (4) Anxiety can also be linked to microbiome species. (5) “Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota–gut–brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic–pituitary–adrenal (HPA) axis early in life, and stress reactivity over the life span.” (5)

More information about POTS & epigenetic changes:

I go into more detail about epigenetic changes, methyl donors and Postural Orthostatic Tachycardia Syndrome (POTS) – a problem that has been occurring for some Covid survivors and a problem I’ve had symptoms of twice and got better from twice – See: Epigenetic changes may also be involved in Covid19 or LongCovid. I prefer being healthy to being unhealthy and I’m willing to work to get better when I can.

Seasoned Peas and Pistachios, with Pomegranate peel.

Peas with pistachios, with cumin and coriander and a little pomegranate peel (inner pith)..

*Pound of frozen Peas, boil for a few minutes with a cup of Pistachios in water to cover the food – then pour off the water. It may contain oxalates from the pistachios. Add a 1/4 cup of fresh water to the drained food along with a half teaspoon of Cumin, Coriander and Gumbo file; one tablespoon powdered or minced dehydrated Pomegranate Peel (inner pith); and simmer with the peas & pistachios for a minute or two to set the Gumbo file thickener and mix the flavors. Serve the peas hot or cold with a little Apple Cider Vinegar and Salt to taste. Makes about four 3/4 cup servings.

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. Alessia Mongelli, Carlo Gaetano, Michela Gottardi Zamperla, et al., Evidence for Biological Age Acceleration and Telomere 2 Shortening in Covid-19 Survivors. medRxiv, April 27, 2021, preprint, https://www.medrxiv.org/content/10.1101/2021.04.23.21255973v1
  2. Clarissa Gerhauser, Impact of dietary gut microbial metabolites on the epigenome. Royal Society, 23 April 2018, https://doi.org/10.1098/rstb.2017.0359 https://royalsocietypublishing.org/doi/10.1098/rstb.2017.0359
  3. Ribosomes, Transcription, and Translation, nature.com/scitable https://www.nature.com/scitable/topicpage/ribosomes-transcription-and-translation-14120660/
  4. Davis CD. The Gut Microbiome and Its Role in Obesity. Nutr Today. 2016;51(4):167-174. doi:10.1097/NT.0000000000000167 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082693/
  5. Stefanie Malan-Muller, Mireia Valles-Colomer, Jeroen Raes, et al., The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders. OMICS J of Integ Biology, Vol 22, 2, 2018, Mary Ann Liebert, Inc. DOI: 10.1089/omi.2017.007 https://www.liebertpub.com/doi/pdfplus/10.1089/omi.2017.0077
  6. Ceci C, Lacal PM, Tentori L, De Martino MG, Miano R, Graziani G. Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid. Nutrients. 2018;10(11):1756. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266224/Published 2018 Nov 14. doi:10.3390/nu10111756
  7. Yan Bian, Juntong Wei, Changsheng Zhao and Guorong Li, Natural Polyphenols Targeting Senescence: A Novel Prevention and Therapy Strategy for Cancer. Int J Mol Sci. 2020, 21, 684; https://www.dropbox.com/s/wckq66cgye3yjr4/ijms-21-00684-v3.pdf?dl=0doi:10.3390/ijms21020684
  8. Kumar Ganesan ID and Baojun Xu, Telomerase Inhibitors from Natural Products and Their Anticancer Potential. Int. J. Mol. Sci. 2018, 19, 13; doi:10.3390/ijms19010013 https://www.dropbox.com/s/xjhguj3dnbop6h2/ijms-19-00013.pdf?dl=0
  9. Triterpenes, sciencedirect.com, https://www.sciencedirect.com/topics/chemistry/triterpene
  10. Xanthones, sciencedirect.com, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/xanthone
  11. Alkaloids, sciencedirect.com, https://www.sciencedirect.com/topics/food-science/alkaloid
  12. Wacker M, Holick MF. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013;5(1):51-108. doi:10.4161/derm.24494 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897598/
  13. CK Eternity, The Truth about Vitamin D Metabolism, Mar 12, 2021, Patreon.com, https://www.patreon.com/posts/truth-about-d-48683534
  14. Bright Light Treatment Research. sunbox.com, https://www.sunbox.com/research/bright-light-treatment-research/
  15. Ezvid Wiki, The 6 Best Vitamin D Lights – 2019, Nov 28, 2018, youtube.com, https://www.youtube.com/watch?v=iqk9hzYC5Mc&feature=youtu.be
  16. Pjrek E, Friedrich M, -E, Cambioli L, Dold M, Jäger F, Komorowski A, Lanzenberger R, Kasper S, Winkler D: The Efficacy of Light Therapy in the Treatment of Seasonal Affective Disorder: A Meta-Analysis of Randomized Controlled Trials. Psychother Psychosom 2020;89:17-24. doi: 10.1159/000502891 https://www.karger.com/Article/Abstract/502891
  17. Spies, M., James, G.M., Vraka, C. et al. Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy. Transl Psychiatry8, 198 (2018). https://doi.org/10.1038/s41398-018-0227-2 https://www.nature.com/articles/s41398-018-0227-2
  18. Elton Alisson, Melatonin produced in the lungs prevents infection by novel coronavirus. Agência FAPESP, Jan 27, 2021 https://www.eurekalert.org/pub_releases/2021-01/fda-mpi012721.php
  19. Dmitry Kats, Tweets & images regarding tryptophan, melatonin, and niacin. “Yes, and melatonin is depleting as a result of tryptophan depleting due to inflammation, and only exclusively sufficient niacin supply can flush this inflammation out to then accordingly restore auxiliary biochem and health” “Funny how melatonin is being pushed through publications in relation to #COVID19, whilst they purposefully censor or “ignore” the inflammatory biochemical mechanism that causes this melatonin deficiency & how sufficient niacin supply nips the inflammation in the bud to restore it” https://twitter.com/NiacinIsHealth/status/1354624867300241408?s=20
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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) (8, 10), B5 (Pantothenic acid) (5), B6 (Pyridoxine) (6, 7), B7 (Biotin), B9 (Folate) (9),
  • Minerals (17): Mg++ (Magnesium) (11, 12, 13), Mn++ (Manganese), K+ (Potassium) (13), Zinc (14, 15), 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.html “The 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
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Kale and carrots – super good right? maybe not for everyone.

The take home point about retinoid toxicity that is mind blowing to this dietitian (last post, & second half of this post) is that kale and carrots and other super nutritious beta-carotene rich foods might be part of the health problem for some people. If retinoid toxicity is occurring due to an enzyme change in the liver then the long held belief that we can’t really overdose on the carrot type of vitamin A may be wrong. Carnivore diet followers though, don’t rejoice too quickly, the animal product foods are sources of the active form of vitamin A and would definitely be part of the problem if excessive retinal was being activated to retinoic acid.

Thanks to everyone who responded to my survey on retinoid toxicity (last post/document). The summary points are that dry skin, seasonal allergies, and fibromyalgia type fatigue are fairly common symptoms and 100% of respondents (including me) were unfamiliar with all of the symptoms. Rewriting the survey and getting approval for research is needed. The initial effort did show that the topic is an unfamiliar one.

Change in the gene expression of enzymes involved in retinal/retinoic acid metabolism has been seen with infection with the Epstein Barr virus. (11) Chronic symptoms for years after an Epstein Barr infection have been known. The range of symptoms that can be due to retinoid toxicity could confuse the diagnosis process – see a dermatologist for the skin, an autoimmune/allergy specialist and a general practitioner might also be involved – would any one of them ask about all the possible retinoid toxicity symptoms? or suggest cutting back on food and supplement sources of vitamin A/beta carotene in order to just test the theory and see if any symptoms improve?

Retinoid toxicity may also help explain why smoking tobacco seems to have a somewhat protective effect against peripheral neuropathy while also being a risk – NAD+ deficiency could mean nicotine is helping provide a source of niacin – so the take home point there would be take niacin to help prevent nerve damage and fatigue (1, 2, 3) without providing smoke toxins that also worsen health risks. (post: Neuropathy can be a cause of extreme tiredness)

Nicotinamide adenine dinucleotide (NAD+)  is an essential pyridine nucleotide involved in energy production within the mitochondria of cells and is protective against harmful effects of oxidative stress ( 2) – the chemical effects of physical or emotional stressors on the body. NAD+ is used in one enzyme involved in vitamin A metabolism. (9)

The following video connects Mast Cell over activity with niacin deficiency. Retinoic acid would add to mast cell activity as it is an activator of mast cells too. Mast cells can release histamine & then there can also be more supplied from foods, or produced in response to foods in mast cells in the intestinal lining. If the Epstein Barr virus causes retinoic acid metabolism gene changes maybe other infections can too. See: First Effective Treatment for Long Covid | Stunning Data from Huge New Study Dec 22, 2020 youtube.com, https://youtu.be/9-3V3h0ncIA  

  • Low histamine/MCAS protocol
  • Niacin, zinc, selenium, vitamin C, D, quercetin, magnesium. – Dr. Ade Wentzel 
  • Anti-histamine medications, over-the-counter generally
  • Prescription medications. Possibly ACE1 and ACE2 blockers, or Mast cell stabilizers or inhibitors.

The chemistry is complex, I am still learning, in the meantime though, cutting back on my daily intake of carrots, kale and then the addition of a lot of mango for a while – DID HELP – when did I ever think that I might be eating too much kale? or mango or my favorite anti-cancer vegetable – the carrot? answer – never. Learning about retinoid toxicity has been unexpected but helpful. Again carnivore diet fans – earlier in my symptom flare up history I found I had to cut out all animal products from my diet in order to get the new skin problem to resolve. Retinoid toxicity may have been a factor that I reduced without realizing why it helped but it worked so I stuck with it.

From a differential diagnosis perspective the range of symptoms that can be a result of retinoid toxicity would likely not be connected to each other. The patient might be seeing an allergy and autoimmune specialist, a psychiatric medical professional and talk therapist, and a general practitioner and as problems worsened a liver specialist, kidney specialist, and a neurologist might be added to the medical team – would they all talk to each other about the amount of carrots and liver in the patient’s average daily diet?

Probably not.

Updates are likely. Document with previous work on MCAS & a copy the survey.

Happy New Year’s Eve Eve!

Celebrating a new year and new health discoveries! (image: fireworks)

Excerpt from previous post – sources/types of vitamin A & retinoic acid

Might an excess or retinoic acid be overstimulating activity in the brain and causing hyperexcitability? (1, 2) Excess retinoic acid can have negative effects in the brain, particularly the hippocampus, (6), the area damaged initially in Alzheimer’s dementia, and may cause cell death. (7)

“The three active forms of vitamin A in the body are retinol, retinal, and retinoic acid.” … “Retinol and retinyl esters are often referred to as preformed vitamin A. Retinol can be converted by the body to retinal, which can be in turn be oxidized to retinoic acid, the form of vitamin A known to regulate gene transcription. Retinol, retinal, retinoic acid, and related compounds are known as retinoids. β-Carotene and other food carotenoids that can be converted by the body into retinol are referred to as provitamin A carotenoids (see the article on Carotenoids). ” (11)

Malfunction of CYP enzymes could increase the risk of excess retinoic acid as they are required to break down the active forms of vitamin A. (12)

Beta-carotene food sources

Beta-carotene, is an inactive form of vitamin A that is generally considered non-toxic, it provides the orange color of carrots, and since it is a fat soluble nutrient it can collect within our skin if eaten in excess and cause an orange color to the skin. (8, 13) It is unlikely to eat enough of the nutrient to cause the skin color change unless regularly drinking juice made with carrots, or kale or other fruits and vegetables that are very rich in beta- carotene. It is unlikely to cause any health problems other than to appear orange for a while (stop drinking so much carrot juice to make it fade). Infants and toddlers who are fed limited numbers of foods but daily may also develop the problem if carrots and sweet potatoes are given consistently instead of including more variety.

Beta-carotene may be broken down to the active retinal form in the intestinal lining or in the liver. (13)

Sources of Pre-formed vitamin A and Provitamin A – beta-carotene and other carotenoids.

“…vitamin A toxicity can occur from either topical or oral use. Oral vitamin A delivery comes in two forms: provitamin A (a prodrug that is metabolized to vitamin A) and preformed vitamin A. Pre-formed vitamin A is obtained from animal food sources, including dairy products and liver, and in most supplements. A list of other foods containing Vitamin A includes milk, cheese, margarine, butter, eggs, chicken, chicken liver, beef, beef liver, processed meats, pizza, fish, and cold breakfast cereals[1]. Provitamin A (beta-carotene and other carotenoids), found in plants such as green leafy vegetables, sweet potatoes, and carrots, must be metabolized to vitamin A. As a result, it is less likely to cause toxicity.” (9) [See Reference list from previous post/document)

From the survey:

  1. Meals and snacks include meats, poultry, fish, milk and other dairy products. [and Vitamin A & D fortified milk equivalent drinks]
    1. Several servings per day typically
    2. At least one serving per day
    3. At least one serving per week
    4. One serving per month or less
    5. No servings of animal products typically
    6. Unknown
  2. Meals and snacks include carrots, tomato products (fresh, or tomato sauce, ketchup, or salsa), sweet potatoes, winter squash or pumpkin, dark green leafy vegetables, cantaloupe, apricots, mango, papaya, peaches, nectarines.
    1. Several servings per day typically.
    2. At least one serving every other day
    3. At least one serving per week
    4. One serving or less per month
    5. No servings of carotenoid rich plant foods typically

*2. Answer 2 is the amount menu planners have as a minimum goal – 1 beta carotene rich produce serving at least every other day.

My own symptoms & diet: I was having several servings of beta carotene rich foods daily and often several times a day, when I had a skin symptom flare up, reducing to the less frequent use helped the skin problem, cheilitis, finally get better. Cheilitis is nonhealing cracks/fissures at the corners of the lips and my problem didn’t get better with more vitamin Bs or iron which deficiencies of can also be a cause., but then got better within a few days of stopping the daily carrot, kale and mango intake. I have one serving occasionally now instead of several daily.

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 – includes excerpts & references not mentioned in the text.

  1. Steve Hill, Niacin Increases NAD+ Significantly in Human Trial. June 8, 2020, lifespan.io, https://www.lifespan.io/news/niacin-increases-nad-significantly-in-human-trial/
  2. Braidy N, Villalva MD, van Eeden S. Sobriety and Satiety: Is NAD+ the Answer?. Antioxidants (Basel). 2020;9(5):425. Published 2020 May 14. doi:10.3390/antiox9050425 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278809/
  3. Griffith GD, Griffith T, Byerrum RU, Nicotinic Acid as a Metabolite of Nicotine in Nkotiana rustica.* J of Biological Chemistry, Vol. 226, No. 12, December 1960 https://www.jbc.org/content/235/12/3536.full.pdf “It appears that the nicotinic acid derived from nicotine enters the metabolic pool and presumably is converted to bound forms such as the pyridine nucleotides, since the dilution of isotope increases somewhat with time.“
  4. Nicotinic acid – an overview. sciencedirect.com https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/nicotinic-acid Niacin, V.K. Lule, … C.D. Khedkar, in Encyclopedia of Food and Health, 2016, https://www.sciencedirect.com/science/article/pii/B9780123849472004839 Interactions of Niacin with Drugs: “Taking nicotinic acid and/or nicotinamide and using a nicotine patch can increase the possibility of becoming flushed and dizzy.” – may increase the risk of the niacin flush reaction, also a side effect risk of the nicotine patch:
  5. Niacin and Niacinamide (Vitamin B3) , webMD.com, https://www.webmd.com/vitamins/ai/ingredientmono-924/niacin-and-niacinamide-vitamin-b3
  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. Luis Rajman, Karolina Chwalek, and David A. Sinclair https://www.cell.com/cell-metabolism/pdf/S1550-4131(18)30122-0.pdf “NMNATs are also attractive targets for raising NAD+ in cells because they have dual substrate specificity for NMN and nicotinic acid mononucleotide (NaMN), and they contribute to both de novo and salvage pathways (Zhou et al., 2002). The green tea compound epigallocatechin gallate has been reported to activate NMNAT2 by more than 100% and NMNAT3 by 42% at 50 mM, although this needs to be confirmed, as no data were presented in the paper (Berger et al., 2005). … An alternative approach to raising NAD+ is to inhibit its degradation either by inhibiting PARPs or NADases, also known as glycohydrolases. The major NADase in mammals, CD38, is inhibited in vitro at low micromolar concentrations by flavonoids including luteolinidin, kuromanin, luteolin, quercetin, and apigenin (IC50 < 10 mM) .” …niacin/niacinamide supp may help reduce risk of kidney injury which involves low NAD+ … bloodflow and muscle and nerve function also may be improved by adequate niacin treatment. … “Since then, numerous studies have reinforced the view that NAD+ levels are key to neuronal function and survival. This includes the dependence on NMNAT2 and its NAD synthesis activity for axonal survival (Yan et al., 2010). ” Supplementing may help protect against Parkinson’s Disease and Alzheimer’s dementia and other neurologic conditions. “NAD-boosting regimens prevent and in some cases can reverse neuronal degeneration associated with hearing loss, prion toxicity, retinal damage, traumatic brain injury (TBI), and peripheral neuropathy (Brown et al., 2014; Dutca et al., 2014; Hamity et al., 2017; Lin et al., 2016; Vaur et al., 2017; Yin et al., 2014; Zhou et al., 2015) ” https://www.cell.com/cell-metabolism/pdf/S1550-4131(18)30122-0.pdf
  8. Fricker RA, Green EL, Jenkins SI, Griffin SM. The Influence of Nicotinamide on Health and Disease in the Central Nervous System. Int J Tryptophan Res. 2018;11:1178646918776658. Published 2018 May 21. doi:10.1177/1178646918776658 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966847/
  9. Seung-Hye Hong, Ho-Phuong-Thuy Ngo, Hyun-Koo Nam, Kyoung-Rok Kim, Lin-Woo Kang, Deok-Kun Oh. Alternative Biotransformation of Retinal to Retinoic Acid or Retinol by an Aldehyde Dehydrogenase from Bacillus cereus, Applied and Environmental Microbiology Jun 2016, 82 (13) 3940-3946; DOI: 10.1128/AEM.00848-16 https://aem.asm.org/content/82/13/3940 “This enzyme converted not only small aldehydes to carboxylic acids but also the large aldehyde all-trans-retinal to all-trans-retinoic acid with NAD(P)+.“
  10. 1.1.1.105: all-trans-retinol dehydrogenase (NAD+). https://www.brenda-enzymes.org/all_enzymes.php?ecno=1.1.1.105&table=Natural_Substrates_Products Epstein-Barr virus lytic infection induces retinoic acid-responsive genes through induction of a retinol-metabolizing enzyme, DHRS9.17244623 From table https://www.brenda-enzymes.org/enzyme.php?ecno=1.1.1.105&onlyTable=Disease
  11. Jones RJ, Dickerson S, Bhende PM, Delecluse HJ, Kenney SC. Epstein-Barr virus lytic infection induces retinoic acid-responsive genes through induction of a retinol-metabolizing enzyme, DHRS9. J Biol Chem. 2007 Mar 16;282(11):8317-24. doi: 10.1074/jbc.M608667200. Epub 2007 Jan 22. PMID: 17244623. https://www.jbc.org/content/282/11/8317.long “Abstract: Lytic Epstein-Barr virus (EBV) replication occurs in differentiated, but not undifferentiated, epithelial cells. Retinoic acid (RA) induces epithelial cell differentiation. The conversion of retinol into its active form, retinoic acid, requires retinol dehydrogenase enzymes. Here we show that AGS gastric carcinoma cells containing the lytic form of EBV infection have enhanced expression of a gene (DHRS9) encoding an enzyme that mediates conversion of retinol into RA. DHRS9 expression is also increased following induction of lytic viral infection in EBV-positive Burkitt lymphoma cells. We demonstrate that the EBV immediate-early protein, BZLF1, activates the DHRS9 promoter through a direct DNA binding mechanism. Furthermore, BZLF1 expression in AGS cells is sufficient to activate DHRS9 gene expression and increases the ability of retinol to induce the RA-responsive gene, CYP26A1. “
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Epigenetic changes may also be involved in Covid19 or LongCovid

Epigenetic changes may be involved in Covid19 and LongCovid, which might be able to be changed back with the addition of plenty of methyl donor vitamins. People with methylation genetic alleles would be more at risk for epigenetic changes to DNA or actin protein filaments. Actin are semi flexible proteins in a double helix shape which support the fluid and organelles inside of cells and around cells and organs of our bodies. Actin also is involved in guiding the work of DNA replication and growth and development of cells or infants.

Methylation is the addition of a methyl group – one carbon atom and three hydrogen atoms, to genes, or actin filaments. A methylated gene is not active for encoding proteins while a demethylated gene is available to be transcribed into a messenger mRNA to be made into a matching protein. Actin filaments are a double helix shape like DNA but do other functions throughout our body. Some have methyl groups also that seem to be essential for proper function of the actin protein whether in muscle contraction or in guiding chemicals within cells to make DNA or do other work. Actin filaments add structure to the jelly like fluid around and in cells and may tether chemicals in place for chemical reactions or guide cellular organization during growth and development.

Actin may be involved with energy fields of our body along with microtubules also, but that is not discussed in greater detail in this post (more information about quantum energy fields and actin is included in Cracking Nature’s Code (2019) (1), and in several posts on another site of mine first in the series, 2nd, 3rd, 4th).

Viral infection and epigenetic changes with a focus on Postural Orthostatic Tachycardia Syndrome and possible dietary and lifestyle changes that may help reverse epigenetic changes is the focus of this post – which got long. It is also available as a section of this document that includes the series on Mast Cells and Histamine. Current standard of treatment for patients with POTS symptoms may leave them unwell for years – a few get better more rapidly. I got better on my own within a few months – twice. More about possible strategies for improvement of epigenetic changes will be included later in the post. More about the epigenetics involved in POTS is included in the Genetics/Epigenetics chapter of my book draft which is available on a platform where you can get an e-copy early (minimum price Free, Leanpub/Tipping The Clock Toward Health) and then be informed of updates with an email subscription.

Viral infection can cause Epigenetic changes.

“Bacterial (Pacis et al., 2015, 2) and viral infection (Lichinchi et al., 2016, 3) directly impact methylation patterns, most likely orchestrated by actin since it is universally hi-jacked in viral infectivity (Cudmore et al. 1997, 4; Ohkawa and Volkman, 1999, 5; Lu et al., 2004, 6; Marek et al., 2011, 7).”

page 34, JB Head, PhD, Cracking Nature’s Code (2019) (1)

I found I have methylation gene alleles in a genetic screening (post: Methylation Cycle Defects – in me – genetic screening “for research purposes only”). Since finding out I stopped taking standard supplements of B12 and folic acid because they are not methylated, not bioactive. I take methyl B12 & methyl folate supplements now. Postural Orthostatic Tachycardia Syndrome (POTS) (9) has been a problem for me in past years a couple times and I got better. Symptoms include a rapid heart rate, tachycardia, and feeling faint or blacking out, especially when getting up quickly from a seated or laying down position to standing. (9) I have heard anecdotal reports of it being a symptom for some LongCovid survivors who had never had the problem before.

To slow the rapid heart rate during an episode I found it helpful to stop and sit or lay down with my feet above my heart if possible and just wait a couple minutes for the rapid heart rate to slow again. Continuing to exercise would make the rapid heart rate worse. Preventing the faintness upon rapidly getting up required trying to remember to slow down and have a support ready to hold if I felt wobbly. I did faint once, odd to find yourself on the floor unexpectedly.

POTS has been found to potentially involve a genetic difference in the norepinephrine transporter gene (SLC6A2) sequence and it can also be an epigenetic problem with links to excess formaldehyde. (9) Formaldehyde can donate methyl groups to DNA that normally would be unmethylated – active. (10) Methylation of DNA is a little like a on/off switch for genes, or the cap on bottle – add the methyl groups and the DNA gene is inactive.

“Formaldehyde as a methyl donor for the methylation of DNA, RNA, and histone acts as an epigenetic factor participating in the reversible and dynamic methylation. DNA demethylation elicits formaldehyde generation in the dividing cells and post-mitotic neurons.” (10) Memory formation involves methylation of DNA and cognitive impairment in older adults is associated with increased internal formaldehyde levels (self-made) and demethylation of DNA. Use of nutrients to remove formaldehyde helped improve memory in an animal based study. (10)

Formaldehyde can be prevalent in secondhand or thirdhand smoke in enclosed rooms, or smog, or we make our own during normal metabolism, and physical or emotional stress conditions may cause an increase, as well as the level potentially increasing in older adults. (11) Elevated levels of formaldehyde within cells causes more breakdown of sugar for energy and increased removal of an antioxidant out of the brain cells, which may increase risk for cognitive damage. “As excess formaldehyde accelerates glycolysis and glutathione export in neural cells, formaldehyde‐induced alterations in brain metabolism and oxidative stress may contribute to the pathological progression of neurodegenerative disorders.” (11)

Formaldehyde is very reactive and can use the methyl group to form links between protein groups or parts that wouldn’t normally be linked – like bungee cords holding parts together in places that would be separate in normal function. (11) Formaldehyde is used with tissue samples to preserve material for viewing under a microscope. Studies of the effect of formaldehyde on the actin protein of live cells that were low on blood sugar found that modifications to the protein did occur – the authors suggest any prior research on the actin protein in formaldehyde treated samples may be inaccurate. (12) Take home point – formaldehyde is not good for our brain cells and may effect the protein of our brain cytoskeleton structure. (12) Protein tangles in brain cells are associated with dementia and autism.

What is a cytoskeleton? We are mostly water, so how do we walk around? With a balance in tension between string like ligaments and muscles and rod like bones of our skeleton. Within the cellular environment, inside and outside the cell membrane – the tent wall, there are rod like microtubules and string like actin protein that is more flexible, it can change shape but isn’t stretchy as much as structurally able to modify in shape. Actin is a double helix, two spirals like DNA except without the ladder like steps joining the two lengths of protein. When force is applied the double helix can get a little longer or shorter as the coils compress or lengthen slightly – tensile strength – and the protein gets stiffer from a side to side direction – torsion – and is less flexible along the length, less able to bend sideways. (13)

The actin protein may act as torsion sensors – is the environment changing in pressure around that section of the protein length – from increased fluid or gas? How full is the balloon like membrane? (14) Channels in a membrane will open and start to leak rather than letting the membrane burst like an overfull balloon. This may seem like a silly discussion – however it is your brain and organs – leaking is better than bursting. Leaking membranes will release fluid and some types of chemicals while a bursting open, as when viral replication is complete and the virus exit a cell, the membrane bursts and all the remaining chemicals in the cell flood into the surrounding cytoskeleton and can cause inflammatory damage to surrounding cells.

These flexible yet firm cytoskeleton actin filaments also may act like guidelines for directing traffic or tethering organelles in place for activity such as replication of DNA during cell division (one cell doubles its DNA and then divides into two cells). Too much of the proteins within a cell nucleus will prevent DNA replication rather than guiding it. (15) Actin is also involved in muscle fiber motion. The double helix structure can also be methylated with methyl groups doing an unknown but critical function. Loss of methylation of actin in one location is associated with cancer and autism spectrum disorders, (16), loss of it in another location along the protein chain is associated with muscle changes that cause female animals to have delivery problems and fewer babies. (17, 18)

So actin is important stringy protein that effects muscle power, cell division, and the brain – and formaldehyde can cause demethylation of DNA, likely it can cause demethylation of actin also which may lead to autism spectrum disorders, cancer, and muscle problems that can affect a healthy delivery of infants (in an animal study). The visual – we want our jelly like insides to have a strong yet flexible tent membrane, tent poles (microtubules), and tie downs (actin) – without having so many tie downs it starts looking like a haunted house full of cobwebs. The amyloid beta protein associated with Alzheimer’s dementia and autism may be protective against a low level infection (post: Magnesium might help protect against beta amyloid placques) but also may increase changes in actin stress fibers (24) and an excess seems to add to chronic inflammatory damage over time.

How do we achieve this? Healthy actin?

It may help promote appropriate methylation of DNA and actin to have adequate antioxidants and methyl donor nutrients in our diet, to reduce oxidative stress chemicals and provide adequate methylation to DNA and actin. Avoiding excessive physical and emotional stress may also be an important strategy, so we aren’t embalming ourselves with self produced formaldehyde (the mummy in the haunted house being our own brain).

We also want to avoid formaldehyde in our environment, which would include improving air quality, especially during sleep hours when our body is focused on detoxification of the brain. Parkinson’s Disease is another chronic condition that may involve epigenetic changes and reducing formaldehyde exposure may be protective. More information is in this post with a link to a longer post about formaldehyde sources: The Cholinergic System

Increasing methyl donor vitamin rich foods and/or supplements should focus on the methylated form if unsure whether there is a genetic allele problem causing lack of methylation.

“Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl group can directly be delivered by dietary methyl donors, including methionine, folate, betaine, and choline.” … “Studies that simulated methyl-deficient diets reported disturbances in energy metabolism and protein synthesis in the liver, fatty liver, or muscle disorders.” … “Hypomethylation has a wide spectrum of effects that include genetic, epigenetic, and metabolic alterations.” (8)

Gastrointestinal problems have been found to be common among patients with Postural Orthostatic Tachycardia Syndrome (POTS) with malfunction or slowing, dysmotility, of the smooth muscle lining of the intestinal tract. “Case study 1: A 20-year-old woman presented to clinic for further evaluation of a several year history of fullness and epigastric discomfort associated with eating and irregular bowel habits. Her weight was stable. She also described frequent migraine headaches, episodic palpitations and lightheadedness with progressively increasing episodes of syncope. A systems review was notable for profound fatigue, dry eyes and mouth and intermittent flushing and pruritus.” (19) The patient’s symptoms include many in common with Mast Cell Activation Syndrome, however testing for mast cell activation was normal. Patients whose symptoms followed a viral infection tend to get better more often than patients with a family history of POTS. (19)  

“A number of chronic conditions are frequently seen in patients with POTS and contribute to symptom burden and reduced quality of life. Common comorbidities include chronic fatigue syndrome, fibromyalgia, interstitial cystitis, and migraine headaches. Other unique conditions that seem to occur with increased frequency in POTS are autoimmunity, the hypermobile form of Ehlers-Danlos syndrome (HM-EDS), and mast cell activation disorder (MCAD).” (19)  

“Unlike mastocytosis, idiopathic mast cell activation [MCAD] occurs in the absence of mast cell proliferation and with episodic accumulation of mast cell mediators in the plasma or urine, usually present when symptomatic. Patients with MCAD typically present with episodic “attacks” of flushing, urticaria and pruritus accompanied by lightheadedness, dizziness, dyspnea, nausea, headache, diarrhea, and/or syncope; symptoms representative of the hyperadrenergic type of POTS with biochemical evidence of MCAD (20).” (19)

The patient in case study 2 had ongoing nausea, vomiting, abdominal pain, and weight loss continuing for years following a viral infection. She was found to have deficiency in iron, zinc, and vitamin B12 and gastroparesis (slow or little intestinal muscle action). Intravenous iron and B12 were provided and an oral zinc supplement. Nutrient levels improved however the GI symptoms and weight loss continued and the patient was given tube feedings which improved weight, however some intolerance to the tube feedings continued and abdominal pain persisted. (19)  

If demethylation of actin protein in the muscle tissue of the intestinal wall was a problem for the patient in case study 2, then it may have been a factor in the gastroparesis. Genetic screening for methylation defects is not mentioned. Supplements of B12 are often an unmethylated form, cyanocobalamin, and which include cyanide. (21) In a study of 12 patients by Huang et al, (22): “Disturbances in GI motility were found to involve not only the stomach, but also multiple segments of the gut spanning the esophagus to the anus.” (19) The commonly used treatments for GI symptoms associated with POTS (see Table 5) do not include nutrients and do include proton pump inhibitors, (19),  a medication that takes the place of magnesium as a calcium channel blocker, and which may lead to worse magnesium deficiency for some people, a genetic difference may be involved. See post: Original Prilosec Warning, edited.

Small intestinal bacterial overgrowth (SIBO) may occur along with GI problems and lead to fat and carbohydrate digestion and absorption problems and bloating from excessive bacterial growth. Changes in diet due to the discomfort are common in patients with POTS and these more severe GI symptoms and which may lead to deficiencies in fat soluble vitamins A, D, E and K. Megaloblastic anemia may result from deficiencies in iron, folate and vitamin B12. (19) Sulfate deficiency may be an underlying factor (23) and providing Epsom salt soaks of the lower legs and feet, or in a bath one to two times a week might help by providing a topically absorbed form of magnesium and sulfate. See post: To have optimal Magnesium needs Protein and Phospholipids too.

Zinc is also involved in DNA methylation and deficiency of the trace mineral can lead to epigenetic changes and gene transcription problems. Zinc is needed along with actin and other proteins to tell the cell nucleus and cell which genes to make into mRNA to be encoded into a protein. “Accumulating evidence has demonstrated that several key enzymes and zinc finger proteins with zinc atom(s) in the reactive center and binding site play important roles in DNA methylation and histone modifications. Therefore, zinc deficiency may disrupt the functions of these enzymes and proteins and result in epigenetic dysregulation. Furthermore, zinc deficiency may enhance inflammatory response and subsequently alter DNA methylation status of the genes involved in inflammation.” (20) Also see posts: Zinc – big news, CoV and other illness related, and Zinc, cancer, and bitter taste receptors.

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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