Cannabinoids are made with the BHMT gene (and others).

Cannabinoids are complex molecules we can make when genetically and nutritionally, healthy and nourished. Various genetic differences are known that cause a deficiency in endogenously made cannabinoids – phospholipids. Lack of cannabinoids negatively effects many areas of health throughout the body and brain, the mood and decision making, and appetite, and movement are all affected by cannabinoid availability.

It is discrimination to prevent research from occurring into the medical benefits of cannabis and cannabinoids and to prevent people who need an external source from having access to it. Covid and LongCovid may be increasing the number of people who might benefit from an external source as epigenetic changes or some other effects of the viral infection may be causing dysfunction in normal production of cannabinoids or some other problem.

Cannabinoids and the Cannabinoid receptors perform many functions in the body.

Membranes and growth of tissue is affected directly as building blocks that are part of the membranes, and indirectly as messenger chemicals that help promote and guide growth.

Cannabinoids also have widespread effects on immune function in addition to brain and nerve function. Cannabinoid receptors are found throughout the brain and also on white blood cells, leukocytes. Our immune function also needs endogenous, internally made, cannabinoids, or would benefit from an external source if endogenous cannabinoids were not able to be made normally.

“In human leukocytes the expression of cannabinoid receptor mRNA has been reported to be lower than that found in brain tissue. The message has, however, been detected in all subsets of leukocytes examined. The message levels are greatest in S cells, followed sequentially by natural killer cells (NK), polymorphonuclear neutrophils (PMN), T8 cells, monocytes and T4 cells.” (11)

Leukocytes help us fight viral infections and patrol for other infectious pathogens or precancerous or cancerous cells. Nutrients work together, synergy – increased power together than any on their own. We need magnesium for leukocytes to be able to perform the killing, apoptosis, and we need niacin to help with the safe removal of debris or engulfing of virus or small cells. Cell contents that are spilt into surrounding tissue has to be removed or it causes more inflammatory damage and can lead to death of other cells.

Niacin reduces inflammation for us in some direct ways and indirectly by inhibiting the NF-kB inflammatory pathway. Deficiency may increase neurodegeneration as well as reduce immune function for fighting virus or cancer.

Reports suggest that deficiency of niacin can increase the risk of neurodegeneration, immunological disorder and inflammation stress [14]. Additionally, niacin exerts its anti-inflammatory effect by suppressing the NF-κB pathway [15].” (18)

The cannabinoid system is also involved in neurotransmitter levels.

According to previous studies, CB1r [Cannabinoid Receptor type 1] is located in the locus coeruleus (LC) and in the dorsal raphe nucleus (DRN), and it regulates noradrenaline (NA) and serotonin (5HT) release, respectively, by the modulation of GABAergic and glutamatergic terminals (117118).” (17)

Problems with the endocannabinoid system can affect mood such as changes in serotonin leading to anxiety or depression. Adequate niacin intake helps preserve our serotonin levels by sparing tryptophan.

Genetic studies pointed out interesting results regarding the involvement of polymorphisms or epigenetic modifications of CNR1 as susceptibility/risk biomarkers to develop anxiety disorders. Lazary and cols. analyzed the interaction of the promoter regions of the serotonin transporter (5HTT; SLC6A4) and CNR1 genes on anxiety. Specific constellations of CB1r and 5HTT promoters were closely associated with high or low synaptic 5HT concentrations, which could result critically in the vulnerability to experience an anxiety disorder (124). Hay and cols. employed CRISPR/CAS9 technology to disrupt a highly conserved regulatory sequence (ECR1) of the gene encoding CB1r (CNR1).” (17)

Cannabinoid system differences occur in ethnic & gender groups. We may be equal but we are not all the same.

Who has the gene differences may vary with ethnicity. “With 60 DNA samples (120 alleles) for each of the 4 ethnic groups studied, we had 90% power to detect a variant allele with a true population frequency of ≥ 2% [16]. ” “Twenty-five SNPs were observed in BHMT — 17 in AA, 8 in CA, 9 in HCA, and 10 in MA subjects (Table 1 and Fig. 2 upper panel).” (1) Number of cannabinoid receptors has been found to vary based on ethnicity and gender with people of Caucasian background having the most, people with African/black background having slightly fewer, and Asian having significantly fewer than those of people with Caucasian or African ethnicity. (11)

The relative levels of the 58 kDa CBI protein 1070 E.S. Onaivi et al. from the male volunteers were, 47.4%; 39.0% and 13.6% for the White, Black and Asian blood samples respectively as shown in Fig. 3. The relative levels of the Cl31 protein in the male and female volunteers were 49.6%, 32.2% and 18.2% for the white and black females in comparison to the black male blood samples respectively as shown in Fig. 4. Therefore in both males and females, the cannabinoid receptors appear to vary by gender and ethnicity, for example Fig. 3 show white male > black male > Asian male and Fig. 4 show white female > black female > black male.” (11)

African Americans were found to have variations in the BHMT gene almost twice as often than Caucasian and Mexican-American ethnic groups and Hans Chinese American were least likely (small group study). (1)

The BHMT gene and Endogenous Cannabinoid production & breakdown.

The BHMT gene encodes an enzyme involved in homocysteine metabolism and the production of amino acids methionine, and dimethylglycine from betaine. (2) The BHMT enzyme is visualized in a graphic of the folded shape, made up of four parts, monomers, coupled into two sets of dimers, figure C: (1.1).

The BHMT enzyme is also involved in about 60% of the glycerophospholipid production pathway (2) which means important cannabinoids may not be able to be made internally and would need to be obtained in the diet or other sources or suffer deficiency symptoms chronically. People with Cystic Fibrosis also can’t make cannabinoids however the fatty acid end of the molecule is what can’t be made normally. The BHMT gene difference would disrupt production of the glycerophosphate end of the larger cannabinoid molecule. PA, PE, PI, and PS production might be reduced or dysfunctional and breakdown of LPC and LPE which might lead to some types of cannabinoids being unavailable and others unable to be broken down and remove normally so excess might collect -unknown by me. (3)

  • Phospholipids: PA, phosphatidic acid; PE, phosphatidylethanolamine; PC, phosphatidylcholine; PS, phosphatidylserine; PG, phosphatidylglycerol; CL, cardiolipin; PI, phosphatidylinositol. (15)
  • LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine, (19)

Research in cannabinoid chemistry was limited to toxicity or addiction due to the rescheduling of marijuana by the Nixon administration as nonmedical. Since the differences in function of the endocannabinoid system varies with ethnic group it is somewhat genetic discrimination to as well as racial discrimination to target an ethnic group with a law that wouldn’t affect all ethnic groups equally. Someone unable to make cannabinoids would have more craving and physical need for a rich source of phospholipids or cannabinoids, than a person with normal ability to make cannabinoids and/or a low or normal amount of cannabinoid receptors compared to someone with many of them.

Cannabinoid receptors effect mood, & may be involved in anxiety, depression, and possibly suicide.

Lysophosphatidylcholine, LPC, can cause an increase in calcium flow into cells at an atypical cannabinoid receptor GPR55 (4, 5) which is excitatory. Over activity, excess calcium entry, might be a negative to cell health. During normal activation levels the atypical cannabinoid receptor has anti-depressant effects and may help prevent suicide as the brains of suicide victims have fewer GPR55 receptors than typical. (14)

This result, plus the observation that GPR55 increases intracellular calcium, suggests that GPR55 activation enhances neuronal excitability. These findings, together with the preferential expression of GPR55 on large-diameter DRG neurons, which can be involved in nociception, particularly in neuropathic or inflammatory pain states (2931), suggest that GPR55 may have a pronocioceptive [pain increasing] role.” (5)

So overactivity of the GPR55 receptors might be perceived as chronic pain and might affect mood and suicidal ideation. Cannabinoid receptors in the prefrontal cortex (CB1) are also known to be involved with suicide risk from research with people suffering from anorexia (17) or alcoholism and depression. (16)

Cannabinoids also can reduce oxidative stress & inflammation, and may be helpful for preventing or treating neurocognitive degeneration conditions.

Calcium can cause oxidative stress damage and would be increased during times of strenuous activity or infection or other times of increased metabolism. THC can cross the blood brain barrier and can help reduce oxidative stress and may be helpful for treatment of neurocognitive degeneration. It was found to improve glucose use within cells and improve brain function in other ways with no toxicity problems in an animal based study. (12)

In silico analysis predicted THC to be permeable across the blood-brain-barrier. THC was also predicted to have an oral LD50 and toxicity class values of 482 mg/kg and 4 respectively. These results indicate that C. sativa improves glucose consumption with concomitant suppression of oxidative stress and cholinergic dysfunction, and modulation of purinergic and gluconeogenic activities in brain tissues.” (12)

Personal experience – I have a double BHMT allele – it isn’t something I would recommend trying yourself.

I have experience of a lifetime without typical cannabinoid production and the symptoms that may cause. There is a double allele of my BHMT gene which means I can not make some endocannabinoids and can’t break down others. A double allele means both copies contain the same difference from typical. (post, see # 3 in the first list) So I can’t make the BHMT enzyme at all. I supplement with dimethylglycine and methionine since finding out and it helped. I need to continue daily though as genetic metabolic differences mean lifelong symptoms of deficiency of the nutrients that are affected, or an excess of a chemical metabolite that normally would be broken down sooner so it wouldn’t collect.

Post: Clinical Endocannabinoid Deficiency, (CED), and phospholipids. Excerpt:

Conditions that may involve Clinical Endocannabinoid Deficiency, (CED):

Conditions that may involve a deficiency in cannabinoids chronically may include symptoms of pain, muscle spasms, nerve numbness, mood disorders, movement disorders, digestive and appetite problems, appetite and growth failure in infants or colic, menstrual problems and infertility/miscarriages and hyperemesis prenatally.

  • Pain/inflammation: Migraines, Fibromyalgia.
  • Mental health: Anxiety, PTSD, Major Depression, Bipolar disorder, Motion Sickness, The balance of cannabinoids (2-AG ~ noneuphoric CBD and anandamide ~ euphoric THC) is a problem in schizophrenia. There is too much of the anandamide, excess THC can cause schizophrenia like symptoms, and providing CBD may help patients. *See this post for more nutritional deficiencies that cause schizophrenia like symptoms, five or more may be involved, suggesting the problem is a symptom rather than a condition with a single cause – and a single cure: The voices that people with schizophrenia are hearing are probably their own inner thoughts.
  • Nervous system: Multiple sclerosis, Diabetic Neuropathy, Brachial plexopathy, Causalgia, Phantom limb pain, Glaucoma, Huntington’s, Parkinson’s, Cystic Fibrosis,
  • Appetite/digestive system: Anorexia & Bulimia, Neonatal Failure to Thrive, infantile Colic, Irritable Bowel Syndrome.
  • Fertility/reproductive system: Dysmenorrhea, Hyperemesis, repeated miscarriages (Russo 2016), (anandamide is needed for implantation of a fertilized egg in the uterus and development of the placenta to occur normally, too much or too little can disrupt the process, Fonseca 2013), male infertility due to sperm motility problems is associated with low levels of anandamide (AEA) (Amoako 2013), (too much can also negatively affect male or female fertility). *See this post for more details about infertility and phospholipids: (Phospholipid or phosphorylation deficiency: Potential symptoms)
  • Other food sources of cannabinoids exist in addition to marijuana or hemp however the amount provided is in lower concentrations so you might need a large salad that includes several sources at one meal, and other sources in beverages, supplements, or at other meals.

— Addition to the excerpt – the amount of cannabinoids in medical marijuana is a lot more, and more likely to be obviously helpful, than the amount of phospholipids or cannabinoids found in a few foods and spices. Sadly medical marijuana has been stigmatized and illegal for many decades. Research into medical benefits was prevented with Richard Nixon’s administration rescheduled cannabis as having no medical value. Research was only possible on addiction or toxicity. Marijuana/cannabis not only has medical value, it has been used medicinally or in other ways by humans for thousands of years. Paper and rope made from hemp fiber was also a large industry prior to making cannabis illegal.

Conditions I’ve had symptoms of which might be due to Clinical Endocannabinoid Deficiency.

The conditions/symptoms I’ve had over my life from the above list include: Migraines, Fibromyalgia; Anxiety, PTSD, Major Depression, Bipolar disorder; Anorexia & Bulimia, Irritable Bowel Syndrome; and some nerve/numbness symptoms since childhood – dystonia.

The amount of cannabinoids a human needs if they are unable to make them internally/endogenously is not readily available information due to the lack of research. The amount of medical marijuana that I find necessary to feel nerve flow in my fingers and throughout my body and to have other symptoms improve is quite a bit each day. It adds up in money to buy, and time and stigma to use.

Smoking is frowned upon by society and cannabis use is still treated as if it is just an addiction or even criminal (which it still is at the Federal level), so it frightens some people to even learn that you use it, or have used it recently. Chronic users have adapted a tolerance to it (8), and mentally may be more used to functioning with some than going without. The type of strain is important for the terpenes that provide different aroma also provide different health effects. Some can be calming for anxiety (limonene), and another sleep inducing and pain relieving (myrcene).

Daily use every 2-4 hours is what I find helpful and smoking has benefits for dosing. Edibles take longer to feel an effect and then suddenly can be too much. Inhalation effects are fairly immediate and easy to know then when enough has been absorbed. The forms of cannabinoids that are absorbed may vary too with the different intake routes, and inhalation may be more effective for some types of health problems than edible/intestinal absorption. The healthiest I’ve ever felt was when I combined eating some fresh trim or immature buds everyday or edibles along with some smoked bud.

Smoke toxins are a negative that causes the “dopey” effect of the stereotypical marijuana user. Vaping devices exist that heat the bud to a lower temperature so the burnt toxins are not created, however some of the THC conversion occurs at higher temperatures so symptoms may not be helped as much. The vape oil products may have other negative effects on the lungs due to the oil and flavorings being inhaled into the lungs where it can add to pneumonia risk.

How much THC am I getting throughout a day then? Possibly 40% of whatever was in the marijuana you smoked – a lot is lost when you burn the buds. 8 There is approximately 525 mg in an eighth of good medical grade marijuana with 15% THC. (6) That eighth ounce might cost $45-60. One gram per day of 10% THC marijuana might provide 40% of the 100 mg of THC it contains, if smoked vs made into an edible. A quarter to half of a one gram joint every 2-4 hours might be giving 10-20 milligrams of THC each time. Strains that also provide some CBD are important as the cannabinoids work together to do somethings in the body such as inhibit mast cell activation.

Eighty to hundred milligrams of THC is suggested as possibly feeling like an excessive dose all at once for someone with increased tolerance, while 25-80 range might be the typical preferred dose. (8)

I have not calculated this for myself before so it does bring up an interesting question of whether I’m getting too much, or enough, or not enough – the fact that I felt best while also eating fresh trim and other edibles regularly would suggest to me that it is not enough when only smoking and that I do need quite a bit daily.

The non-euphoric CBD has been found safe for use even at 1500 mg per day, though 20-40 mg might be more typically used. (7)

Dronabinol is a capsule form of a THC like medication and it might be prescribed at a 2.5 mg dose twice per day. That might seem like a lot to a new user and not that big of a dose to someone else, although the lack of CBD may be a problem if anxiety is a side effect.

Tolerance levels can reduce after not using for a while and then build back up again. Doses that would seem intense for a new user would not really affect a long term user. (8) Genetics may play more of a role in these differences too, lack of research leaves some questions unasked.

Genetic differences occur in the number of cannabinoid receptors which can effect tolerance for a concentrated source such as medical marijuana.

There can be genetic differences where a person doesn’t make cannabinoids well and has lots of extra cannabinoid receptors, all wanting/ready for cannabinoid activation – but with none or to little available. They might tolerate and prefer a larger dose of THC. Other people might have normal amounts of cannabinoid production and like a smaller dose or none, might not like it. For me it provides feeling throughout my body in a way that I don’t have otherwise. It helps me for muscle knots or spasms and pain. Mentally it helps me with PTSD and anxiety and prevents mast cell histamine excess and hyperexcitability.

Cannabinoids help with learning & forgetting – reshaping nerve pathways – neural plasticity. Pain signal pathways can also be remade more easily with cannabinoids.

Cannabinoids help with learning and nerve flow, and with forgetting – changing nerve pathways to build new as needed and remove the old as they are not needed (old phone number for example). Neural plasticity – changing nerve pathways and synapses between nerves is a function involving cannabinoids. Pain and movement, appetite and growth, cannabinoids affect many functions of the body and neural plasticity can affect pain pathways too – remembered pain in an amputee’s healed wound, and maybe feelings of the missing limb still being there also.

The same team noted a baseline fragility of serotonergic systems in migraine and fibromyalgia [89], plus the co-occurrence of primary headache in 97% of 201 fibromyalgia patients. In a later study [67], they supported the concept that both disorders represented a failure of serotonergic analgesia and NMDA-mediated neuronal plasticity.” (9)

Synergy – many nutrients work together to perform any action in the body. Magnesium also helps inhibit excess pain nerve signals.

Pain conditions can be caused by deficiency of nutrients or chemicals that inhibit pain sensing nerves. Magnesium is needed to inhibit them as well as cannabinoids. Migraine pain may be not responsive to opiate pain killers. (9)

A trigeminovascular system has long been implicated as integral to the pain, inflammation and secondary vascular effects of migraine, linked through the NMDA/glutamate system [49]. Cannabinoid agonists inhibit voltage-gated calcium channels, and activate potassium channels to produce presynaptic inhibition of glutamate release [50], without dissociative effects noted with other NMDA inhibitors, such as ketamine.” (9)

*Having adequate potassium and magnesium in the diet and avoiding excess glutamate in seasonings and other dietary sources can also help avoid migraines – in addition to the cannabinoids or cannabinoid receptor agonists – activators.

Diabetes pain may also not be helped by opiates unless magnesium is also provided – and providing magnesium in a larger dose helped even more! (10)

Give the body what it needs to function and it functions. Miracle!

Sunshine might be part of the miracle too – vitamin D represents a group of chemicals which may aid us in ways we don’t know yet. Supplementing with one – vitamin D, may not be providing us others that we would have made if sun or full spectrum/UVB containing light is available. (13)

We need cannabinoids too – and some of us genetically can’t make them – since birth, and potentially – epigenetic changes might be occurring that cause dysfunction in a person’s ability to make cannabinoids at some point later in their life. Is that happening in LongCovid survivors? -discussed in the last post.

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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    1. Figure 3, https://europepmc.org/articles/PMC2515933/figure/F3/
  2. BHMT Gene (Protein Coding), Betaine–Homocysteine S-Methyltransferase: BHMT Pathways & Interactions, genecards.org, https://www.genecards.org/cgi-bin/carddisp.pl?gene=BHMT#pathways_interactions
  3. Glycerophospholipid biosynthesis, reactome.org, https://reactome.org/PathwayBrowser/#/R-HSA-1483206
  4. Drzazga A, Sowinska A, Krzeminska A, Rytczak P, Koziolkiewicz M, Gendaszewska-Darmach E. Lysophosphatidylcholine elicits intracellular calcium signaling in a GPR55-dependent manner. Biochem Biophys Res Commun. 2017 Jul 22;489(2):242-247. doi: 10.1016/j.bbrc.2017.05.145. Epub 2017 May 26. PMID: 28552522. https://pubmed.ncbi.nlm.nih.gov/28552522/
  5. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A. 2008;105(7):2699-2704. doi:10.1073/pnas.0711278105 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268199/
  6. Understand Cannabis Weights & Calculate THC Dose, June 5, canuvo.org, https://canuvo.org/cannabis-weight-calculate-thc-dose/
  7. CBD Dosage: Figuring Out How Much to Take, healthline.org, https://www.healthline.com/health/cbd-dosage#safety-and-side-effects
  8. Barreda AR, De Leon K and Urmasa S., A simple guide to pot, THC and how much is too much. April 20, 2018, latimes.com, https://www.latimes.com/projects/la-me-weed-101-thc-calculator/
  9. Russo, Ethan. (2008). Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?. Neuro endocrinology letters. 29. 192-200. 10.1522/cla.roj.let. https://www.researchgate.net/publication/5448843_Clinical_Endocannabinoid_Deficiency_CECD_Can_this_Concept_Explain_Therapeutic_Benefits_of_Cannabis_in_Migraine_Fibromyalgia_Irritable_Bowel_Syndrome_and_other_Treatment-Resistant_Conditions
  10. M. Bujalska, H. Makulska-Nowak, S.W. Gumuka,  Magnesium ions and opioid agonists in vincristine-induced neuropathy, Pharmacol Rep. 2009 Nov-Dec;61(6):1096-104. http://www.ncbi.nlm.nih.gov/pubmed/20081245
  11. Onaivi ES, Chaudhuri G, Abaci AS, Parker M, Manier DH, Martin PR, Hubbard JR. Expression of cannabinoid receptors and their gene transcripts in human blood cells. Prog Neuropsychopharmacol Biol Psychiatry. 1999 Aug;23(6):1063-77. doi: 10.1016/s0278-5846(99)00052-4. PMID: 10621950 https://www.researchgate.net/publication/12692236_Expression_of_cannabinoid_receptors_and_their_gene_transcripts_in_human_blood_cells
  12. Erukainure OL, Matsabisa MG, Salau VF, Islam MS. Tetrahydrocannabinol-Rich Extracts From Cannabis Sativa L. Improve Glucose Consumption and Modulate Metabolic Complications Linked to Neurodegenerative Diseases in Isolated Rat Brains. Front Pharmacol. 2020;11:592981. Published 2020 Nov 24. doi:10.3389/fphar.2020.592981 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774498/
  13. Vitamin D and your health: Breaking old rules, raising new hopes. Updated May 17, 2019, Published Feb. 2007, health.harvard.edu, https://www.health.harvard.edu/staying-healthy/vitamin-d-and-your-health-breaking-old-rules-raising-new-hopes
  14. Wróbel A, Serefko A, Szopa A, Ulrich D, Poleszak E, Rechberger T. O-1602, an Agonist of Atypical Cannabinoid Receptors GPR55, Reverses the Symptoms of Depression and Detrusor Overactivity in Rats Subjected to Corticosterone Treatment. Front Pharmacol. 2020;11:1002. Published 2020 Jul 8. doi:10.3389/fphar.2020.01002 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360849/
  15. Image/ Figure “General structure of phospholipids and common head groups.” source: Membrane lipids in Agrobacterium tumefaciens: Biosynthetic pathways and importance for pathogenesis researchgate.net, https://www.researchgate.net/figure/General-structure-of-phospholipids-and-common-head-groups-PLs-contain-two-fatty-acids_fig1_261605192
  16. Hungund BL, Vinod KY, Kassir SA,, et al., Upregulation of CB1 receptors and agonist-stimulated [35S]GTPS binding in the prefrontal cortex of depressed suicide victims. March 2004, Mol Psychiatry 9(2):184-90 DOI: 10.1038/sj.mp.4001376 https://www.researchgate.net/publication/8692237_Upregulation_of_CB1_receptors_and_agonist-stimulated_35SGTPS_binding_in_the_prefrontal_cortex_of_depressed_suicide_victims
  17. Navarrete Francisco, García-Gutiérrez María Salud, Jurado-Barba Rosa, et al., Endocannabinoid System Components as Potential Biomarkers in Psychiatry. Frontiers in Psychiatry Vol 11, 2020, 31 pp, DOI=10.3389/fpsyt.2020.00315 https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00315/full
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  19. Lysophosphatidylethanolamine, sciencedirect.com, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/lysophosphatidylethanolamine

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)

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.

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.
*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+.

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.

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/
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  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

COVID19, summary of nutrients that might help prevent, treat, recover.

I had untested Covid19 like illness Feb/March prior to when testing was available. Antibody testing wasn’t available until 3 months later and it was negative at that time. My symptoms and timeline matched the description of the still novel illness. Due to my autoimmune illness history I already was familiar with and using daily, many phytonutrients, in addition to other nutrients.

I managed to get better on my own but the symptoms got into breathless asthma like problems with non-productive cough before I started recovering and my history of colitis-like/inflammatory bowel symptoms also flared up but I was also familiar with what foods could help get that back under control instead of worsening. Severe diarrhea can be deadly too and a percentage of Covid patients did have bowel symptoms too, see the pomegranate peel section below for a link. (More specifics on my illness: Treatment vs a ‘Cure’.

Twenty two other nations besides the United States are distributing medications, nutrients, and/or therapeutics, for early at home treatment for their citizens. (rcm.imrpress.com)

Citrus Peel and Bioflavonoids

Patients could be helped with some non-toxic, inexpensive, readily available nutrients and phytonutrient foods. Bioflavonoids – citrus peel – was what I added to my routine as the non-productive cough got worse – within 10-20 minutes the mucus had loosened and my airways opened and I could cough it out. Vitamin C, chewable 100 mg (what I had), also soothed my sore throat and helped with breathing. The serving of citrus peel to open the airway (lots of research on bioflavonoids for asthma exists) that I found helpful was about 2 teaspoons of orange zest every few hours or one navel orange peeled with a sharp knife so the white pith was left on the orange instead of being removed. (citrus peel posts)

Powdered bioflavonoid is readily available for purchase in bulk and the inner pith is mild – it could simply be added to foods for patients still able to eat. Bitter taste receptors in the lungs are activated and cause thinning of the mucus, opening of airways, and increase in cilia moving the mucus up and out of the lungs. Bioflavonoids are also a source of some vitamin C, quercetin, and a variety of flavonoids that may also be available as single nutrients such as hesperidin and that might help patients who could only be given nutrients intravenously (Evaluation of the Intravenous and Topical Routes for Ocular Delivery of Hesperidin and Hesperetin). Like vitamin C, hesperidin and other flavonoids can help reduce risk of vascular problems. 

Zinc Ionophores, anti-viral, anti-microbial.

Quercetin and EGCG, found in green tea and pomegranate peel, have similar anti-viral mechanism of action as Hydroxychloroquine & Ivermectin, though those medications have other anti-viral action also. Pomegranate peel also has other mechanisms of action as an anti-viral. The inner peel is milder than the outer rind and both are sources of potent phytonutrients. The inner peel can be chopped fresh or dried and powdered to add to soup or salads in small amounts, about one to two tablespoons for a recipe. The outer peel is more bitter and can be used to make a tea/extract, simmer gently for about 20-30 minutes. Overheating too long deactivates some of the medicinal nutrients.

Niacin and other B vitamins have anti-viral power, and are needed to help with energy level and reducing inflammation.

Adequate B vitamins are also important for preventing vascular and other symptoms. Thiamin (needed in higher amounts during an infection, Operation Thiamine – Reducing the Need for Hospitalization of Patients with COVID-19.), riboflavin, and niacin also have anti-viral action. The niacin can be very effective at higher doses, given in the ‘flush’ form, building up to 1000 mg day. (Sufficient Niacin Supply: The Missing Puzzle Piece to COVID-19, and beyond?.)

Symptoms of low niacin/B3 include dermatitis, skin rash or dryness, the lower legs in particular may show the skin symptoms; diarrhea; and worsening deficiency can cause dementia, and ultimately death if left untreated. See: Pellagra: dermatitis, dementia, and diarrhea.

Niacin (nicotinic acid) Protocol against COVID-19,
shared with permission of the author, Dmitry Kats, PhD.
*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.

For more about the benefits and possible risks for a few types of people, which might be reduced by the additional use of quercetin, see the post: Niacin, & early treatment in general for SARS-CoV-2 is sensible, reduces hospitalization and mortality rate.

People with a methylation gene difference may be at more risk because the methylated folate and B12 are essential for homocysteine metabolism. Excess homocysteine is a cause of atherosclerosis. Sulfate and vitamin C are also needed for preventing excess homocysteine (Review: Chemical Pathology of Homocysteine. V. Thioretinamide, Thioretinaco, and Cystathionine Synthase Function in Degenerative Diseases)

An overview paper describes the role the various B vitamins have in reducing inflammation and/or helping us fight a viral infection: Be well: A potential role for vitamin B in COVID-19.

Magnesium helps white blood cells kill infected cells & protects the brain from inflammation risks.

Epsom salt, magnesium sulfate, can be absorbed through skin pores (any studies about magnesium chloride not being that well absorbed have little to nothing to do with the absorbability of a hydrated magnesium sulfate molecule). The sulfate is bioactive and patients would also be helped by the magnesium. Magnesium is nature’s calcium channel blocker and so would help protect against cell damage from excess calcium being allowed into cells. Magnesium is also essential for white blood cells to be able to perform apoptosis, killing infected cells and removing them safely. Poor intestinal absorption is not uncommon and topical magnesium or intravenous may help, especially if muscle cramps are a symptom. Lab tests showing hypokalemia can also suggest low magnesium is a problem. (Mechanism of Hypokalemia in Magnesium Deficiency – JASN)

Magnesium also is needed as a calcium channel blocker to protect against stimulation by EMF energy which can also open the calcium channels. (Klinghardt pdf) See post: EMFs and Intracellular Calcium – Magnesium is nature’s calcium channel blocker. For the long hours of sleep in particular it can help reduce inflammation risk to remove or turn off WiFi devices from the sleeping area or nearby rooms. Various products are available that block EMF such as cell phone cases and modem covers which help reduce excess energy release, (educateemf.com/WiFi Router Guards) turning it off while sleeping would be ideal if possible.

The SARS-CoV-2 virus can add viroporins to the infected cell’s membrane which allows calcium to enter. The excess calcium within a cell causes the creation of NLRP-3 inflammasomes which produce cytokines that increase inflammatory changes in other cells, (“pro-inflammatory IL-1β cytokines“). (Klinghardt/3/19/2020,pdf) The viroporin channels vary somewhat for different virus and one type is blocked/inhibited by the anti-viral medications “amantadine and rimantadine.” (viroporins) Adequate magnesium would help protect other cells if/when an infected cell burst open to release the newly replicated virus from the infected cell. Phytonutrients that may help inhibit NLRP-3 inflammasome assembly are listed towards the end of this post: Phytonutrients that may help against SARS-CoV-2.

Avoiding EMF exposure would help by not adding more activation of our own calcium channels and promoting even more entry of excess calcium into all of our cells (our whole body being exposed to the EMF somewhat equally depending on the source, or more to our ear/hand if holding a smartphone). (Klinghardt/3/19/2020,pdf)

Blackout curtains or an eye mask for sleeping or napping can help with eye sensitivity and may help the body make more melatonin which has protective effects against viral infection and inflammasome production. Vitamin C also reduces inflammasome production and can reduce over negative effects on blood vessels. (Klinghardt/3/19/2020,pdf)

Zinc helps us make antibodies and immune cells, and has antiviral power when given with a zinc ionophore.

Zinc is needed to make mature T-cells and for the thymus gland to make antibodies. Zinc is needed for the gene transcription of bitter (and other) taste receptors. Patients who have lost their sense of taste and smell may be experiencing zinc deficiency. Zinc is involved in protein replication and zinc ionophores are antimicrobial because of the ionophore carries the zinc to cells with excess iron (sign of infection or cancer) and help the zinc enter the cell where the zinc then disrupts protein replication – so no virus will be made. The current nutrient guidelines for zinc are likely half what an elderly person needs to promote thymus gland function. During an acute infection more can be given safely but high dose zinc can accumulate so is not for long term use. (jenniferdepew.com/zinc) (other nutrients that may promote T-cells)

Zinc ionophores that have been found effective in many other nations of the world include hydroxychloroquine and ivermectin. Hydroxychloroquine has been safe and effective if given within the first few days to week of symptom onset and ivermectin has been found helpful in preventive, early treatment, and later stage treatment. Phytonutrient zinc ionophores that I was using anyway include quercetin and EGCG from pomegranate peel (my primary source – it is a main research interest of mine) or green tea. (effectivecare.info/pomegranate)(Pomegranate peel – anti-COVID19, may block ACE2 receptor access to the SARS-CoV-2 virus)

  • Ivermectin, a zinc ionophore, has helped in South America and elsewhere, review.
  • Hydroxychloroquine is also a zinc ionophore and has also been found effective given early with zinc and azithromycin: study .
  • Quercetin and EGCG are phytonutrient zinc ionophores that also have shown some benefit as antivirals against SARS-CoV2 and are available in foods and as herbal supplements.

Zinc is also needed for beneficial intestine microbes. Poor gut health has been linked to severe COVID19.

Zinc is also critically important for having a healthy microbiome – intestinal bacteria that help us instead of harming us. Beneficial species use as much as 30% of the zinc from our diet and if our daily diet is consistently low in zinc then more harmful species that don’t need zinc will grow instead. (Chronic Dietary Zinc Deficiency Alters Gut Microbiota Composition and Function, ) Poor gut health has been linked to more severe COVID19. (New Research Shows Poor Gut Health Connected to Severe COVID-19 – Probiotics May Help Patients)

Vitamin D deficiency has been found in as many as 80% of patients with severe COVID19 – it is needed for immune function & reducing risk of an over reaction that is inflammatory & can lead to long term autoimmune disease.

Vitamin D has been clearly shown to be a factor in severe COVID19 (an early study, April 2020) and it is unclear to me why the population as a whole is not being encouraged to take vitamin D and zinc right away – both are needed before an infection ideally. The vitamin D helps reduce risk of an autoimmune type cytokine over-reaction and the zinc is needed to make antibodies and help T-cells to change from immature to functional.

Studies … show an increased risk of infection in those with low vitamin D levels and a 25 to 30-fold reduced risk of ICU admission and a substantial reduction risk of death in older COVID-19 patients supplemented with vitamin D.” ~ Dr. Dan McCartney

Vitamin D and SARS-CoV-2 infection—evolution of evidence supporting clinical practice and policy development, McCartney et al, 2020. (quote via @mercola)

Low vitamin D levels has been associated with a greatly increased risk of death from severe COVID-19. Levels of vitamin D above 33 ng/ml seems most protective and the greatest risk seen with levels below 27 ng/ml according to one study. (Raharusun et al, an early study, 4/2020)

Low vitamin D levels were significantly associated with increased risk of death from severe COVID19 illness. Levels above 33 ng/ml seem most protective against mortality risk.
Results of the age-adjusted clinical study by the working group of Dr. Prabowo Raharusun,” Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study, an early study, 4/2020.

Standard nutrient guideline dosing of vitamin D may be adequate for protection but it needs to be prior to exposure to the infectious pathogen. Defense doesn’t help as much after an allergic/autoimmune over-reaction already developed. A review found that moderate dose supplements in advance helped reduce risk of respiratory infection by as much as 50%, while mega dose supplements of vitamin D taken after the respiratory infection had already begun were not significantly helpful. (Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data) The vitamin D3 form is more bioactive than the vitamin D2 form that is more typically available in one-a-day type supplements, if you have a choice about what to buy.

Pomegranate peel has anti-viral effects, a zinc ionophore and other phytonutrients that have brain protecting effects, and it can help intestinal health.

Pomegranate peel is a good source of hydrolysable tannins which can be healing to mucus membranes/GI tract) in smaller amounts and an irritant in larger amounts, also a diuretic, so dosing does matter – but I had colitis like flare-up with my CoV-like illness and my bean soup with a little pomegranate peel and Gumbo file was very soothing. The second half of this post has a list of hydrolysable tannin sources and mucilaginous foods or seasonings, which include Gumbo file: ACE2, Diarrhea, & COVID19 – it gets complicated.

Selenium deficiency is also more common in patients with severe COVID19.

Selenium deficiency has also been associated with more severe COVID19. Iodine is needed for immune function but I haven’t seen a direct finding of deficiency associated with severe CoV19. Vitamin A deficiency causes lack of immune function but excess conversion to active retinoic acid within the liver may be a factor in LongCovid – I have improved my health post CoV by reducing beta-carotene foods and I already had cut out all animal products during a previous autoimmune flare-up which helped. At the time I suspected I had developed an albumin autoimmune problem but maybe vitamin A was involved. I am still reading on this topic, very complex (Retinoid Toxicity)

Omega 3 fatty acids are anti-inflammatory and may help protect against death from COVID19.

Omega 3 fatty acids are the type found in fish oil, known also as EPA and DHA, and precursor, ALA, found in plant sources such as walnuts, flax seed meal and Black Currant Oil. Patients with severe COVID19 who had higher levels of omega 3 fatty acids had lower risk of dying of the infection than people with lower levels. (nutraingredients-usa.com) Omega 2 fatty acids EPA and DHA have been found to be made into a endogenous cannabinoid form that has anti-inflammatory benefits. (Emerging Class of Omega-3 Fatty Acid Endocannabinoids & Their Derivatives)

Post recovery may have fatigue from anemia of chronic inflammation and worse symptoms may involve overproduction of the active form of vitamin A – retinoid toxicity.

The liver changes that lead to overproduction of active vitamin A can occur with Epstein Barr viral infection. I had mononucleosis in high school and chronic fatigue type symptoms since then, off and on. Post recovery this March I was still extremely fatigued and it felt like anemia of chronic inflammation/infection to me and I added artemisinin twice a day as an iron chelator and it helped within just a day or two, I was able to start going on short walks outside instead of feeling like the bedroom to the kitchen was too much exercise. (Artemisinin, arteannuin-B, sgp130Fc and COVID-19

Pain hurts. Health is better. We need all of the nutrients for health and in much greater amounts for some during illness. During health we make the antioxidant equivalent of 300 oranges – during illness we may no longer be able to do so, but we can’t eat 300 oranges, two teaspoons of citrus peel would have more antioxidants than one orange.

Resources with dosing recommendations for early or preventive self care by medical groups or professionals.

Regarding dosing for supplements – see an individual health care provider for individual guidance and here are some recommendations by medical groups or medical professionals:

  • Immediate Treatment for Early Stage SARS-CoV-2 Infections Recommended To Be Supported Nationally Starting Now,  Authored by Ben Kaplan Singer, M.D.; Daniel Stickler, M.D.; Avery J. Knapp Jr., M.D.; with many contributing doctors.  (googledoc)
  • TCM Treatment of COVID-19, based on extensive experience in Chinese hospitals, by Adam Tate, March 20, 2020, updated March 25, 2020. (medicinetraditions.com) — This document includes a description of the progressive or varying stages of COVID19 illness. It includes examples of symptoms that occur in the different stages, and herbal recipes recommended for the specific stage and symptom set. The Chinese medical professionals have found that a combination of the traditional medicinal herb mixtures and modern medicines to be more effective than either alone for treating patients with more severe COVID19 infections. 
  • EVMS Critical Care COVID-19 Management Protocol, Developed and updated by Paul Marik, MD (17)
  • The Zelenko Protocol with over-the-counter self care and clinician guidance for the medication dosing is available here: Zelenko Protocol. For prevention: Zelenko COVID-19 Prophylaxis Protocol.
  • Dr Klinghardt’s COVID-19 Prevention & Treatment Guidance Summary, (website/to download pdf) (pdf) (summary pdf)
  • Physician Secrets Revealed: Outpatient Treatment For Covid-19, By Peter A. McCullough, MD, MPH (physicianoutlook.com)

A graphic summary of care guidance said to be used in Australia was shared on a social media site (harley_carter1). The protocol recommends Ivermectin, zinc, doxycyline, Montek-LC, Paracetamol for fever (better known as acetaminophen in the US). However I am unsure of the specific origin other than the site on the screen shot: (thecompleteguidetohealth.com/ivermectin.html#AUSTRALIA).

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.