Histamine excess may affect long Covid sufferers.

Histamine may be a familiar word for seasonal allergy sufferers. Anti-histamine medications may be used during pollen season for those with a itchiness and a runny nose. Others may have a year long sensitivity as the problem can also be genetic, due to less of the enzyme that is needed to breakdown histamine. The diamine oxidase enzyme, (DOE), is available as a supplement that can be taken with meals. (1)

We make our own histamine in response to allergy type sensitivities. Mast cells are part of the immune system that might become overactive and produce more histamine than we want during pollen season – or possibly after having experienced an infection such as COVID19. People experiencing odd symptoms months after seeming to recover from the worst of the respiratory and other symptoms of COVID19 may be experiencing excess histamine and mast cell overactivity. See this video for more information: Nicola Haseler interviewing Dr. Tina Peers regarding histamine and overactive mast cells after COVID19 recovery (LongCovid). (7)

Dr. Bruce Hoffman discusses Mast Cell Activation Syndrome – overactivity of the immune Mast cells in more detail. Lab tests for histamine, or other chemicals involved in the inflammatory response are not necessarily reliable and may require a refrigerated centrifuge, which may not be standard lab equipment. The problem may involve genetic susceptibility but not necessarily, anyone might develop symptoms given a combination of stressors. Emotional or physical stress, lack of sleep, and the foods we eat may over activate mast cells throughout our body or within the mucosal lining of the Gastrointestinal tract (from the mouth, already the way through). Someone with recent bowel illness, may have a short term reduction in the diamine oxidase enzyme needed to break down histamines in food. The enzyme is produced in the lining of the intestinal tract.

…we’re inundated, so to speak, with multiple stresses far more than our capacity to withstand them. Our immune system, it just gets triggered because of multiple stressors. And there are many triggers for mast cell activation. Poor sleep. Stress is one of the biggest triggers. Food, I mean, food is incredible in its ability to trigger the mast cells…” […] “So education is first. Second is to try and identify the triggers that trigger their mast cell activation. And this is one of the greatest challenges because there are many triggers from, you know, hot, too much heat, too much cold, stress, poor sleep, as mentioned. And then we get into the more obvious triggers, chemicals, heavy metals, dietary antigens, and then infections or inflammatory triggers like mold.” – Dr. Bruce Hoffman (8)

Family history may also be a factor, trauma for the person may have left them with an identity of illness; or trauma earlier in the family’s history may have left epigenetic changes. Changing diet and lifestyle, and pursuing health can be a lot of work, and which may even be resisted as the patient improves, (psychoneuroimmunology). Misdiagnosis of the physical problem as a somatization disorder (“it is all in your head”) may also be a problem according to Dr. Hoffman. (8)

The itchiness is not in my head – it is all over my body.

How do you even be a healthy person if you have never known health, nor has your family? What do people do all day? Go for a walk, without sneezing – cook delicious food that doesn’t leave you with a mystery headache later on – so many choices, but change can be difficult.

We also get some from foods that contain histamine naturally. Other foods may have increased content as it ages – fresh is best for people with histamine excess. (4) Freezing a larger batch of food in meal size portions might be a sensible way to prepare fresh foods (that don’t have food additives or seasonings that you need to avoid). Fermented foods such as yogurt, saurkraut and kombucha are popular currently, for the goal of improving intestinal health and the microbiome, (the balance of beneficial bacteria and other microbes within the GI tract). However they may make someone with overactive mast cells worse instead of better. Vitamin C may help. (8)

Avoiding foods that contain histamine or may increase our tendency to make more can help allergy sufferers or the people with the genetic difficulty breaking down the excess. Symptoms can include headaches as well as itchiness and runny nose. Fatigue may also be a problem as well as other odd symptoms or chronic pain. Anxiety and schizophrenia symptoms may worsen with excess histamine. (1, 3, 4)

There is plenty of information on the topic available so I will link to it rather than try to replicate it here. Several of the articles make the point that the problem is additive and histamine is not something you can avoid all together. Small amounts or a taste may be okay, but several foods or beverages over the course of the day may lead to an uncomfortable headache that evening. (3)

  • Amy Myers, MD, provides an overview of the food lists of foods to avoid, or consider eliminating and then adding back to check tolerance, a list of lower histamine foods, symptoms that may be linked to excess histamine, and a list of medications that may be increasing histamine, amymyersmd.com. (1)
  • People with histamine food sensitivities may also be sensitive to lectins, oxalates, and pesticides. Foods more likely to be low or high in histamines are also labeled with a code for lectin (L), oxalate (O), or pesticide residue ![food] on a website by Beth O’Hara, a Functional Naturopath, mastcell360.com. This includes the most extensive food list and includes seasonings and food additives to avoid, or which might be less of a concern to use. (2)
  • Brief list of symptoms that may occur, along with foods to avoid, and a sample day’s menu of lower histamine foods. (3)
  • Extensive list of symptoms or physical traits that may be associated with people with a lifelong sensitivity to histamine is included in this article about histamine. Mood problems of increased anxiety are not uncommon for people with histamine intolerance problems. Sleep problems may also be a concern. (4)
  • Tracking your symptoms and daily food is recommended by this site, histamineintolerance.org.uk; Food List: (5), the Food Diary is a downloadable link from this page: (6).
  • Medications, lab tests for diagnosis, and nutrients or phytonutrients that may help if the individual is not overly sensitive to them already are discussed in detail in the interview with Dr. Hoffman, audio or the transcript or available on Dr. Hedberg’s website: (8) . Dr. Hoffman also makes the very important point that an apparent ‘drug’ sensitivity might really be a reaction to other components of the tablet or capsule, or even contaminants, which is also something to look at on labels for other supplements and over-the-counter medications. Psychoneuroimmunology and the effects of trauma on the brain, and possible cognitive therapy approaches are also discussed in more detail.

Writing down your daily foods, beverages, and symptoms can be a good way to watch for patterns in what seems to make you feel better or worse. Food sensitivities can also vary with how much stress you are experiencing and whether you slept well, or drank enough water. Once you are more familiar with your patterns and know which foods and habits are helpful then recording your daily foods and symptoms may no longer be necessary.

Health is worth it. Happy dining, and good sleep to you!

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. Amy Myers, MD, Histamine Intolerance: What You Need to Know, amymyersmd.com, https://www.amymyersmd.com/article/histamine-intolerance/
  2. Beth O’Hara, Low-histamine diet: How it can benefit you and what to eat, Low and High Histamine Foods Lists mastcell360.com https://mastcell360.com/low-histamine-foods-list/
  3. How to follow a low-histamine diet. Nov 13, 2018, houseofwellness.com.au, https://www.houseofwellness.com.au/health/conditions/follow-low-histamine-diet
  4. Histamine, histamine-sensitivity.com, https://www.histamine-sensitivity.com/histamine.html
  5. The Food List, histamineintolerance.org.uk, https://www.histamineintolerance.org.uk/about/the-food-diary/the-food-list/
  6. The Food Diary, histamineintolerance.org.uk, https://www.histamineintolerance.org.uk/about/the-food-diary/
  7. Long Covid + Histamine / MCAS – Dr Tina Peers in conversation with journalist Nicola Haseler. Oct. 16, 2020,
    nicola haseler, youtube.com https://youtu.be/vr2bb0b4X14
  8. Mast Cell Activation Syndrome with Dr. Bruce Hoffman, interview by Dr. Nikolas Hedberg, https://drhedberg.com/mast-cell-activation-syndrome-dr-bruce-hoffman/

Zinc deficiency more frequent for severe Covid-19

To recap from recent posts – zinc is needed for thymus gland function, which is needed to make antibodies; zinc is needed for immature T-cells to mature into immune cells that can kill infectious pathogens or infected cells; zinc is needed to make bitter taste receptors which are needed for many functions throughout the body in addition to being on our tongue and sensing the bitter tasting phytonutrients in our foods, or bitter tasting toxins which we need to avoid.

Older adults may need about double the zinc that is the US recommendation (it is the same for all adults) in order to have thymus gland function. (5) Excess zinc can build up to a toxic level but that is more likely to occur in amounts of 50 milligrams/daily or more regularly.

In Covid-19 it has been found that zinc deficiency is more common for patients with more severe symptoms. The author’s words:

  • “Patients with coronavirus disease 2019 (COVID-19) had significantly low zinc levels in comparison to healthy controls.
  • Zinc deficient patients developed more complications (70.4% vs 30.0%, p = 0.009).
  • Zinc deficient COVID-19 patients had a prolonged hospital stay (7.9 vs 5.7 days, p = 0.048).
  • In vitro studies have shown that reduced zinc levels favour the interaction of angiotensin-converting enzyme 2 (ACE2) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and likewise that increased zinc levels inhibit ACE2 expression resulting in reduced viral interaction.”
  • COVID-19: Poor outcomes in patients with zinc deficiency. (Jothimani et al, 2020) (1)

Zinc deficiency having a role in more severe COVID19 illness was suspected earlier in the outbreak and details about the correlation between the symptoms is available here: (6).

Some good news – early treatment, within four days of symptom onset, using hydroxychloroquine (HCQ), zinc and the antibiotic azithromycin, was found to reduce mortality rate significantly for patients with COVID-19 and no heart problem side effects were experienced by the patients using the experimental protocol (HCQ/zinc/az.). (2)

More good news – there does seem to be T-cell immunity for people who have had other coronavirus infections in the past. (3) T-cell immunity is more flexible than antibody/antigen type of B-cell immunity. T-cell immunity tends to react against a group of similar type pathogens.

Phytonutrient rich foods or some types of phytonutrient supplements, and zinc and other nutrients, can help the body’s immune system to make a beneficial balance of T-cells instead of having more inflammatory types that are less helpful against a direct intracellular infection such as a virus. See this document for more details on foods and supplements that may help the immune T-cell function: (4)

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. Dinesh Jothimani, Ezhilarasan Kailasam, Silas Danielraj, et al., COVID-19: Poor outcomes in patients with zinc deficiency. International Journal of Infectious Diseases, Vol 100, Nov 2020, Pages 343-349 https://www.sciencedirect.com/science/article/pii/S120197122030730X
  2. Roland Derwand, Martin Scholz, Vladimir Zelenko, COVID-19 outpatients – early risk-stratified treatment with zinc plus low dose hydroxychloroquine and azithromycin: a retrospective case series study. Int J of Antimicrobial Agents, Available online 26 October 2020, 106214 https://www.sciencedirect.com/science/article/pii/S0924857920304258
  3. Peter Doshi, Covid-19: Do many people have pre-existing immunity? BMJ 2020;370:m3563 https://www.bmj.com/content/370/bmj.m3563
  4. Depew J, Foods and phytonutrients that may benefit T cells. https://docs.google.com/document/d/1wXIZfyynEWAvTyOhvPX-iI7QJ5jyHbAj8t5yA0p-55Y/edit?usp=sharing
  5. Cabrera ÁJ. Zinc, aging, and immunosenescence: an overview. Pathobiol Aging Age Relat Dis. 2015;5:25592. Published 2015 Feb 5. doi:10.3402/pba.v5.25592 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321209/
  6. Inga WesselsBenjamin Rolles, Lothar Rink, The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis. Front. Immunol., 10 July 2020 | https://doi.org/10.3389/fimmu.2020.01712 https://www.frontiersin.org/articles/10.3389/fimmu.2020.01712/full

Artemisinin, arteannuin-B, sgp130Fc and COVID-19

I’m more of a blogger, or early Christmas present giver, than may be ideal for a book author. I’ve been working on a section of my new book that might be beneficial for SARS-CoV-2 prevention and COVID-19 treatment. It may also help explain what makes some people more susceptible for developing severe COVID-19 illness rather than remaining asymptomatic as others who test positive for the SARS-CoV-2 virus.

The book is in very early stages but is 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. I’m copying the artemisinin section here in case it may be helpful. The theme of the book is not CoV specific so the excerpt is also including it within a larger topic.

The too long;didn’t read – a different extract of wormwood, arteannuin-B, may be a more effective anti-viral and anti-inflammatory, than the artemisinin; while the artemisinin may help with a chronic anemia of inflammation type iron overload problem, which may occur with COVID-19 recovery or when the illness is severe. Artemisinin has also been found useful for autoimmune disease and possibly as a cancer treatment. The bigger CoV specific information is a theory about interleuken-6 (IL-6) and a genetic difference that may explain why some people can be asymptomatic carriers of the virus – their immune system doesn’t overreact to IL-6 – and for those more at risk for over-reacting a protein our body normally makes (sgp130Fc) may be an effective treatment because it would just be needed in the overactive amount (five times the normal level).

Merry Christmas – I never could save a present I bought early.

Autoimmune Disease and other Chronic conditions

What if you are feeling so sick that nothing seems cheerful? There are no guarantees that eating healthier will be a cure-all, however you don’t know without trying and some symptom relief might be possible at least. Giving time a chance to help may also help. It can take seven days for the intestinal lining to start to heal and longer for most other areas of the body. Take care of your brain because most types of brain cells do not get replaced regularly the way that cells throughout the rest of the body are retired and replaced with new cells. The advantage in the foods and phytonutrients that tip the body away from inflammatory pathways and towards the production of antioxidants and increased immune function is modulation – moderation.

Immunomodulators and other types of modulating chemicals can shift the activity slightly towards more active or less active. An overactive immune system can also be dangerous. Modulation can be moderate – just the right amount of activity. The healing foods and phytonutrients may help moderately increase immune activity without over activating it into an autoimmune level of action. And they may moderately inhibit the inflammatory pathways without suppressing them totally as may occur with immunosuppressive drugs. During an infection we need the inflammatory pathways but we do not need an overactive response.

Too many inflammatory chemicals can lead to their attacking our healthy body cells in an immune response called a Cytokine Storm or Sepsis Shock. An autoimmune over-reaction may involve molecular mimicry where a food protein or other substance that is similar to our own body’s chemicals sets off an allergic type of immune response against the body chemical, not just the dietary protein.

Wormwood, Artemisia annua, an anti-malarial herb used in Traditional Chinese Medicine, and source of Artemisinin and arteannuin-B .

Wormwood is a medicinal herb used in Traditional Chinese Medicine (TCM). An extract of it is used to treat malaria. Artemisinin, the extract, has also been found to help modulate the immune system, which may be helpful for the treatment of autoimmune disease. Derivatives of artemisinin have also been studied for use as antiviral and anticancer treatments. (52⁸⁷) White blood cells can help identify, kill, and remove infected, damaged, or cancerous cells in a process called autophagy however the response can also become overactive in the case of autoimmune disease or a cytokine storm.

Immunomodulating herbs and drugs can help stimulate an immune response while also inhibiting too large of a response. Artemisinin was found to be helpful for rheumatoid arthritis, which has been shown to be due to a pathogen with an intracellular form, (53⁸⁸), and not helpful for osteoarthritis which is due to overuse or other physical trauma. (54⁸⁹) Artemisinin is a phytonutrient extract of the herb wormwood. It is used as a malaria treatment and in Africa ten grams of the dried herb may be used daily as a prevention against malaria, a mosquito borne parasitic disease affecting blood cells. (55⁹⁰)

The whole herb, wormwood (Artemisia annua), may contain other phytonutrients with stronger anti-viral effects than artemisinin, as whole herb extracts were found more effective against the SARS-CoV-2 virus than artemisinin alone (cell-based study). The World Health Organization (W.H.O.) expressed concern that use of a whole herb extract for non malarial illness in the population might result in an increase in artemisinin-resistant malaria strains. (56⁹¹) That concern may be overlooking the synergistic – additive – effect phytonutrients within a plant may have.

Many plants have phytonutrients that work together beneficially, helping health in different ways that have an additive effect: one may help offset a negative effect of another, or one may help one symptom and another might help a different symptom. Ginger root, for example, has over 400 bioactive phytonutrients.

Artemisinin chemically is a sesquiterpene lactone – an aromatic terpene. Two strains of Artemisia annua were chemically analyzed and found to have slightly different ratios and types of sesquiterpenes and terpenes, (57⁹²) so other aromatic chemicals in the whole herb may also be helping health in various ways. One in particular, arteannuin-B, has been found to work with artemisinin against the malaria parasite in a combination that was more effective than if the artemisinin was used alone. (58⁹³) Switching to a whole herb extract or using the combination of arteannuin-B and artemisinin might reduce the risk of the malaria parasite becoming artemisinin resistant instead of increasing the risk about which the W.H.O. expressed concern. (56⁹⁴)

Bioactive – chemicals with some biological effect within our bodies, it might be beneficial or harmful for a particular person depending on the person’s underlying level of health or genetic differences, or gender, age or other factors.

Artemisinin chemically is attracted to cells with excess iron which infectious microbes need for growth and so do cancer cells. The phytonutrient can stop protein replication within the iron rich cell which stops the replication of the infectious microbe. It also seems to bind with the excess iron which in itself can cause oxidative damage – rust might be a more familiar term for oxidative damage affecting iron. If Rheumatoid arthritis is due to an intracellular pathogen then artemisinin may be helping by stopping the underlying infection. It can help in cancer because cancer cells also tend to have extra iron and it may be helpful for the anemia of chronic inflammation which also involves excess iron in cell storage instead of being used to carry oxygen within red blood cells and may be involved in symptoms of extreme tiredness during later stages or recovery from an infection.

The amazing thing about artemisinin in comparison to other antimalarial medications is a low toxicity risk comparatively. Healthy cells are not targeted. Normal function does not seem to be disrupted although it may have pro-inflammatory effects. Arteannuin-B, on the other hand, has been found to have significant anti-inflammatory effects:

Arteannuin-B inhibits the LPS-activated production of PGE2 four times more than artemisinin or dihydroartemisin, and it has a strong inhibitory effect on the proinflammatory interleukines IL-1β, IL-6, TNF-α.”. (Lutgen 2013, 58⁹⁵)

Reducing interleukin-6 levels would likely be helpful for treating COVID-19 illness. It is increased by the SARS-CoV-2 virus and by the infection process naturally. It can help fight infection and has pro and anti-inflammatory types. A protein (sgp130Fc) helps control the pro-inflammatory type but it is normally present in amounts lower than would be needed during later stages of COVID-19 illness (the name of the disease caused by an infection with the SARS-CoV-2 coronavirus, a new virus in the group of cold and influenza viruses). Providing sgp130Fc as a treatment may help treat the people with the more severe inflammatory reaction. There seems to be a genetic susceptibility regarding the over sensitivity to IL-6 levels which may help explain why some people don’t get very sick and others get severely ill with a SARS-CoV-2 infection. (59⁹⁶)

Recent studies about polymorphism within the IL-6R genes, showed how some IL-6 Receptor variants could be a much better substrate for the shedding protease ADAM17, resulting in a reduced response to inflammation and infectious states, in terms of sIL-6R increase [68]. Those individuals are also protected from many chronic inflammatory diseases [69].” (59⁹⁷)

This theory, if true, could help point out who is more at risk for a severe immune reaction to a SARS-CoV-2 infection – people with chronic inflammatory diseases – it suggests they have the more active immune response by their IL-6 Receptor. Knowing who is more at risk can help identify who needs to be more self-protective and who may benefit from preventive treatment or early treatment for suspected symptoms. And they may be the people who might be helped by providing the protein sgp130Fc that inhibits the pro- inflammatory IL-6 Receptor. There is enough of the inhibiting protein to block the receptor activity during normal health but the level of IL-6 can increase five-fold during an infection – while no extra sgp130Fc is made. The excess IL-6 starts inflammatory activity in surrounding cells creating an increasing inflammatory response. (59⁹⁸)

Panic? Or use the information about our genetic immune responses and infection risks to be more proactive about our own health? or our communities’ health?

We can defend from within by providing our bodies with the extra nutrients that our unique genetic metabolism or infection or disease may require for our cells to cope. Vitamin C and other antioxidants and phytonutrients can also help reduce IL-6 and other inflammatory chemicals.

~~~~ end of book excerpt as it was written

addition: The protein sgp130Fc has also been found helpful to treat an animal model of Rheumatoid arthritis. The treatment used was 2.5 mg/kg which was given intravenously to the animals daily three weeks after the induction of the disease condition. Thy hypothesis that the treatment would also improve vascular health in the animals was not disproved. (60) Vascular health is commonly negatively effected in Rheumatoid arthritis along with the symptoms of swollen and painful joints, typically starting in the fingers and toes and progressing to the feet and ankles.

The protein sgp130Fc may also be helpful for treating ulcerative colitis and Irritable Bowel Syndrome. It is tested in human clinical trials for the two bowel conditions by Ferring Pharmaceuticals and I-MAB Biopharma. The version of the protein being produced and tested by the pharmaceutical companies is being called Olamkicept. (61)

The protein may also affect the risk of Alzheimer’s dementia or other inflammatory brain conditions. The protein does not cross the blood brain barrier but affects throughout the rest of the body may still affect the brain by causing an increase of soluble interleuken-6 Receptors which then can increase brain inflammation. The spg130Fc would need to be delivered into the brain somehow to inhibit the soluble IL-6 R and reduce inflammation. (61)

Maybe it would help reduce the amount of the soluble IL-6 Receptors that would be available to enter the brain if given intravenously within general circulation, I don’t know enough about this topic. It is nice to have some hope though. Previous treatment approaches for Alzheimer’s dementia have focused on reducing amyloid protein and it has not been found very helpful for improving the condition.

Pomegranate polyphenols (ellagic acid) can cross the blood brain barrier after metabolism by intestinal bacteria transforms them into urolithins. (62) Pomegranate peel extract also has been used to help form nanoparticles. Urolithin a is being given orally as a nanoparticle to help reduce oxidative stress during treatment with the cancer drug cisplatin. Mortality rate improved in an animal-based study with the addition of the urolithin a. (63) Maybe a combination of spg130Fc and urolithin could cross the blood brain barrier.

Cautions for use of spg130Fc may be needed if liver disease is present, and use for cancer treatment would be dependent on the specific cancer type. It might help treat some types and worsen other types. (61)

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Reference List