This text was beforehand printed December 20, 2020, and has been up to date with new info.
“The Immunity Fix: Strengthen Your Immune System, Fight Off Infections, Reverse Chronic Disease and Live a Healthier Life” is a guide written by James DiNicolantonio, Pharm.D., with whom Ico-wrote “Tremendous Gasoline,” and Siim Land, an esteemed biohacker and writer of “Metabolic Autophagy.”
In it, they evaluation how you can enhance and regulate your immunity — a subject that ought to be excessive on anyone’s listing nowadays. The catalyst for this collaboration was a lot of tutorial papers written by DiNicolantonio on the underlying causes for why some folks endure worse COVID-19 outcomes.
Many who find yourself with extreme sickness produce low quantities of Kind 1 interferon. There’s additionally a discount of their adaptive immune system. In consequence, they do not clear the virus shortly and find yourself having to depend on a extra proinflammatory killing of the virus inside their cells as an alternative.
Immune System Fundamentals
As a refresher, your immune system consists of two major “arms”:
- The innate immune system, which is your first line protection made up of pure killer (NK) cells, macrophages and white blood cells like neutrophils
- The adaptive immune system — T cells, and B cells that produce antibodies
As defined by DiNicolantonio:
“We used to suppose that the adaptive immune system was this method that takes some time to kick in, and after you have immunity out of your adaptive immune system, then you could have a longer-term safety, which is true. Nevertheless, the adaptive immune system additionally appears to have cross sensitivity, that means in case you’ve been uncovered to earlier coronaviruses, your T cells appear to have some cross sensitivity to SARS-COV-2.
So, primarily, what we see is a discount in T cells, within the cytotoxicity of those CD8 T-killer cells, which kill viruses in a pleasant, apoptotic, managed approach.
When you could have a discount in these sorts of immune cells, you must rely extra in your proinflammatory innate immune system for clearing viruses — issues like neutrophils, white blood cells, macrophages. They kill in a way more pro-inflammatory, non-specific approach, they usually find yourself killing wholesome bystander cells.
What we predict is occurring is, primarily, you could have this discount in Kind 1 interferons … which intrude with the virus. And on the similar token, you could have a discount in B cells and T cells. So, what finally ends up occurring is you do not clear the virus as shortly, and you find yourself having this proinflammatory killing.
Siim and I collaborated as a result of this stuff are advanced. We have to get this in layman’s phrases. What our guide boils all the way down to is that your weight-reduction plan and your way of life management these sorts of issues, and there is issues that you are able to do to help your individual immune system.”
Your T cell perform tends to say no with age. It is also lowered in these with persistent illness. Lowered T cell perform seems to be a major reason behind extreme COVID-19, seeing how these with the worst COVID-19 outcomes are the aged and/or these with comorbidities comparable to diabetes, hypertension, metabolic syndrome and heart problems.
These elements worsen the proinflammatory response that you just get from SARS-CoV-2, however additionally they weaken your immunity on the whole. “The Immunity Repair” evaluations way of life methods that aid you sidestep and forestall this proinflammatory response. “It is a very holistic method to trying on the immune system,” Land notes.
Prime Two Nutrient Deficiencies to Handle
Food plan and dietary supplementation are two key methods that may assist increase your immune perform. In accordance with Land and DiNicolantonio, vitamin D could also be a very powerful nutrient on this respect. Vitamin D prompts greater than 2,000 genes, DiNicolantonio notes, together with vitamin Okay-dependent proteins and restore genes. It additionally helps your physique produce highly effective antimicrobial and antiviral peptides.
These over the age of 60 have a ninefold better danger of dying from COVID-19 than that of youthful people. Should you’re severely vitamin D poor, your danger will be 15fold better. So, whilst you can not change your age, you’ll be able to actually alter your vitamin D standing, thereby probably minimizing your danger.
Nevertheless, with the intention to convert the vitamin D into its lively kind, you want magnesium, so magnesium would most likely be the second-most vital nutrient deficiency to deal with. Magnesium can be required for immune cell perform, so in case your magnesium stage is low, your immune perform could possibly be impaired.
“Individuals who have genetically low magnesium of their pure killer (NK) cells and their CD8 T-killer cells … their immune system is down. They’ve persistent activation of Epstein-Barr, which 95% of us are contaminated with, they usually’re at a a lot larger danger of lymphoma,” DiNicolantonio says.
“And that is only one nutrient. Being poor in a single nutrient can probably trigger this immunodeficiency primarily. So, within the guide, we undergo how vitamins and your immune system work together and why nutrient deficiencies are most likely resulting in lots of these poor COVID-19 outcomes.”
Zinc and Selenium Are Additionally Essential
When it comes to significance, zinc would most likely nab the third spot. Taking zinc lozenges on the first onset of chilly signs has been proven to chop the period of the widespread chilly by six to seven days, however you must take it appropriately.
“Should you’re utilizing lozenges, you must take it each two hours,” DiNicolantonio explains. “You bought to take it inside 24 hours of symptom onset. You must take about 18 milligrams per dose, and you must get the whole each day dose over 75 milligrams.”
Fourth on the listing could be selenium. Not solely is selenium deficiency related to a fivefold larger danger of dying from COVID-19 and a threefold larger danger of getting a poor COVID-19 consequence, however additionally it is related to coxsackievirus-induced cardiomyopathy (Keshan illness).
So, in case you’re poor in selenium, a nonvirulent RNA virus known as coxsackievirus, which generally solely causes hand, foot and mouth syndrome in sure kids, can turn into way more virulent, resulting in virally induced cardiomyopathy. Sufferers with this cardiomyopathy, generally known as Keshan illness, are sometimes given selenium. Selenium can be vital for the manufacturing of glutathione, which seems to play a big position in COVID-19.
The Significance of Melatonin
One other factor that’s related to improved COVID-19 outcomes is melatonin. DiNicolantonio explains:
“Melatonin is fascinating. I sort of view it like molecular hydrogen however with some further benefits. Melatonin can freely cross into any cell membrane, in order that’s very key. If you wish to get to the oxidative stress, you could have to have the ability to entry it and get into the mitochondria. Melatonin and molecular hydrogen are two molecules that may try this and actually try this nicely …
Melatonin isn’t just this hormone we secrete within the mind. We synthesize it from serotonin, and it may be produced in lots of cells. So, it is lively all through all the day. What’s fascinating is that it is one of many solely molecules that appears to extend the transcription of Nrf2.
Most plant polyphenols and all these different Nrf2 boosters solely inhibit the inhibitor of Nrf2, which is KEAP1. Basically, they’re making the present Nrf2 ranges extra lively. If you add melatonin, that will increase the transcription of Nrf2. Only a few molecules can truly try this.
And Nrf2 is how we increase our endogenous antioxidant enzymes. Actually, that is the important thing. You probably have acute respiratory misery, you wish to increase your total endogenous antioxidant programs, and the easiest way to do tha is thru Nrf2 activators, notably melatonin.”
Excessive-Dose Melatonin Reduces COVID-19 Mortality
As for dosage, a current case collection involving 10 sufferers with COVID-19-related pneumonia used 36 to 72 mg of oral melatonin per day in 4 divided doses, which is way larger than beneficial for sleep. DiNicolantonio feedback:
“It is so protected. Doses of melatonin as much as 1,000 mg per day in people have proven just about no unwanted effects moreover grogginess and sleepiness … Melatonin use is related to an 83% discount in mortality from COVID-19, a 30 to 50% discount in testing constructive for SARS-COV-2, and in a case collection of 10 COVID pneumonia sufferers, it lower the period of hospital keep by 5 days.
And none of these sufferers who bought melatonin ended up on a mechanical ventilator or died whereas in comparable extreme COVID-19 circumstances that have been hospitalized on the similar time, 25% to 40% of these people ended up on mechanical ventilators or died.”
As defined by DiNicolantonio, melatonin is actively produced all through the day and is a grasp antioxidant, that means it scavenges free radicals. It additionally binds to melatonin receptors that upregulate your innate antioxidant protection programs.
“Melatonin truly appears to pay attention within the bone marrow and that is vital as a result of your immune system comes from stem cells produced out of your bone marrow,” DiNicolantonio explains.
“From these stem cells, you get your immune cells. A few of your immune cells may even produce melatonin. We predict it is being concentrated within the bone marrow to guard immature stem cells and immune cells from oxidative harm, which truly makes lots of sense.”
Nebulized Hydrogen Peroxide
Whereas Land and DiNicolantonio hypothesized that inhaled molecular hydrogen at 2% or 3% could be a possible vital technique in COVID-19 sufferers requiring air flow in a hospital, this may be considerably costly. A greater various, for my part, could be nebulized hydrogen peroxide, which you are able to do at house. That is my private go-to technique, and I’ve seen many get well from COVID-19 utilizing this technique.
You’ll be able to evaluation my video under for extra detailed in formation.
Nebulizing hydrogen peroxide into your sinuses, throat and lungs is a straightforward, simple technique to increase your physique’s pure expression of hydrogen peroxide to fight infections and can be utilized to help the immune system.
All you want is a desktop nebulizer, food-grade hydrogen peroxide and a few saline. That approach, you could have every little thing you want and might start remedy at house on the first indicators of a respiratory an infection. Consider meals grade hydrogen peroxide should be diluted all the way down to a 0.1% dilution earlier than use.
I imagine the hydrogen peroxide works like a signaling molecule, and should even have some direct viricidal impact on the cells within the lining of the lungs and the sinuses the place the virus takes maintain initially. So, you are probably killing it instantly, plus supporting your immune responses.
Handle Your Metabolic Well being
Along with addressing nutrient deficiencies, particularly vitamin D, magnesium, zinc and selenium, Land stresses the significance of optimizing your metabolic well being.
“Analysis [has found] that metabolic syndrome, weight problems and diabetes, all these issues, worsen the outcomes of COVID-19 in addition to different infections like influenza. Weight problems additionally will increase the period you could carry the virus and share it for longer. So, it is particularly unfavourable in a society that tends to be in poor metabolic well being.
One fascinating factor that we found through the writing of the guide is that one of many molecules that will get activated throughout an an infection is named HMGB1, which stands for Excessive Mobility Field-1.
That will get activated throughout an an infection, and it is one of many key molecules that sort of offsets the cytokine storm by activating NFKB and NLRP3 inflammasome and finally causes this huge pro-inflammatory cytokine response …
What we theorized primarily based on this analysis, is that hyperglycemia, insulin resistance, elevated blood sugar will make it extra probably that HMGB1 goes to get into the cell and activate NFKB and these different pro-inflammatory cytokines that may finally result in the cytokine storm.”
The Case for a Low Linoleic Acid Food plan
DiNicolantonio and I mentioned the significance of avoiding seed oils in our guide, “Superfuel.” In it, we dove deep into the significance of wholesome fat for metabolic well being, and the harmful nature of linoleic acid-rich vegetable oils.
Linoleic acid (LA) is likely one of the most perishable molecules in meals, that means it is extremely vulnerable to wreck. When it oxidizes, it turns into oxidative metabolites known as oxidative linoleic acid metabolites or oxylipids or OXLAMs that harm proteins, DNA and cell membranes and are probably the first wrongdoer of persistent illness.
OXLAMs additionally activate pathways that destroy your immune response. What we did not totally respect on the time was that even wholesome oils, comparable to olive oil, can have a unfavourable influence, due to their LA content material. LA can be excessive in conventionally raised rooster, as these animals are sometimes fed LA-rich grains.
Should you exceed 10 grams of LA per day, and maybe as little as 5 grams — no matter their supply — chances are you’ll radically worsen your metabolic well being. From a historic perspective, 150 years in the past, the common consumption of LA was 2 to three grams. Right this moment, many get greater than 30 grams a day from their weight-reduction plan. For my part, an LA-restricted weight-reduction plan stands out as the single most vital dietary intervention out there.
“That is an important level, and I believe from a COVID-19 perspective, the largest factor you wish to do is enhance the resilience of your cells to oxidative stress. Sadly, in case you’re consuming a weight-reduction plan excessive in LA, and if it would not get burned for gas and it will get saved in tissues, the half-life of LA is 680 days, and it will possibly begin oxidizing the mobile membranes, together with in your immune cells as nicely.
Should you enhance your omega-6 consumption, that impacts the degrees in your immune cells. And in case you saturate your immune cells with this oxidized LA, you are most likely at a a lot larger danger of secreting extra proinflammatory cytokines in your individual cells, and your lungs and your arteries are most likely way more vulnerable to the harm that happens when our physique tries to kill off viruses.
I am certain if we have been to really take a look at the blood ranges of oxidized LA in extreme COVID-19 sufferers, they’d be sky excessive … So yeah, it is probably an enormous driver of total irritation.”
Easy Methods to Enhance Your NAD+ Degree
One other vital molecule is nicotinamide adenine dinucleotide (NAD+), which will be elevated utilizing precursors comparable to nicotinamide mononucleotide (NMN) and/or nicotinamide riboside (NR).
NMN seems to be the superior of the 2, because it prompts a salvage pathway. Nevertheless, you need not take an costly complement to enhance your NAD+ stage. Methods comparable to train, sizzling or chilly publicity and time-restricted consuming — which prices you nothing — can get the job completed. Land explains:
“A variety of the NAD that your physique produces is recycled by means of the salvage pathway. Little or no (lower than 1%) of it will come from meals, particularly tryptophan or niacin.
The best technique to forestall shedding your NAD as you become old or as you get immunocompromised is to advertise the salvage pathway, and one of many activators of this NAMPT enzyme that governs the salvage pathway is AMP protein kinase (AMPK), and AMPK will get primarily turned on by catabolic stressors within the physique, comparable to train, sauna, chilly, in addition to fasting.
What I’ve concluded is that doing this common intermittent fasting or timed consuming is a really environment friendly approach of retaining our vitality ranges excessive and stopping the decreasing of the opposite issues that decrease NAD, like irritation and oxidative stress.
The issue is that NAMPT is managed by sirtuins and sirt1 particularly. Sirtuins are longevity genes. Sirtuins additionally management your circadian rhythms. So, what I believe is that in case your circadian rhythms are misaligned, in case you’re doing shift work otherwise you’re jet lagged or one thing, then sirtuins will not be going to be expressed, and additionally, you will then inhibit NAMPT, which can then shut down the NAD salvage pathway.”
In different phrases, when sirtuins are suppressed from mismatched circadian rhythms, you additionally suppress NAMPT, because the NAMPT requires sirtuins to work. Sirtuins additionally eat NAD, so in case your NAD stage is low, you are not going to get the advantages sirtuins present.
“I believe the supplemental NR and NMN are very helpful in case you’re in an NAD-deficient state as a result of the issue is that in case you’re already low in NAD, then it is laborious to lift that bar since you’re already so low and depleted,” Land says.
“In case your NAD is excessive, you then expertise the much less unfavourable unwanted effects from irritation oxidative stress as a result of your physique can restore and take care of it, whereas in case you’re immunocompromised, you are very outdated or you might be simply nutrient poor and have low NAD, then it is a vicious suggestions loop. So, utilizing one thing like a NAD precursor or a booster could be a fast repair to get your self again heading in the right direction.”
Should you use an NAD or NMN complement, take into account getting it in suppository kind. Different options embrace subcutaneous or intranasal administration, all of that are simpler than oral dietary supplements. That stated, as famous by DiNicolantonio, in case your NAD is low, your finest wager is to deal with the underlying trigger reasonably than merely including dietary supplements.
“Finally, any kind of oxidative stress goes to deplete NAD. So, repair your metabolic dysfunction and enhance your nutrient deficiencies first, and in the end your NAD want goes to go down. Repair the issues which are inflicting you to burn by means of your NAD.”
One of the crucial widespread sources of oxidative stress is electromagnetic subject (EMF) publicity, which is the subject of my guide “EMF*D.” Two major enzymes eat NAD. One is poly ADP-ribose polymerases (PARP), which is often known as adenosine ribosyl transferase (ARTD). PARP is used to restore DNA harm, and each time PARP is activated, it makes use of up 150 molecules of NAD.
The excellent news is that methods comparable to sauna, train and fasting not solely will enhance the manufacturing of NAD, but additionally will scale back the consumption of it. These methods additionally decrease irritation, which in and of itself will decrease your NAD consumption.
Different Advantages of Sauna Bathing
Along with preserving your NAD, sauna bathing additionally mimics a fever, which is your physique’s first-line protection in opposition to infections. DiNicolantonio explains:
“The rationale why we induce a fever to struggle an an infection is as a result of that permits our cells to secrete warmth shock proteins. To ensure that a virus to copy, it has to contaminate your cell, hijack your equipment, and it has to export its ribonucleoprotein advanced out of the cell to copy. To ensure that that advanced to get exported, the M1 protein has to dock onto it.
Warmth shock protein 70, which will get launched throughout sauna periods, can mix to the viral ribonucleoprotein advanced stopping M1 protein from docking. [By] inhibiting the export of that viral ribonucleoprotein advanced, [heat shock protein] primarily inhibits viral replication.”
In accordance with Land, common sauna bathing and train are among the many finest issues you are able to do to strengthen your immune system and enhance your physique’s resilience. The 2 are additionally complementary.
Train causes preconditioning hormesis, so in case you train earlier than your sauna, you then considerably bolster your physique’s capability to deal with an infection and different stresses. The warmth will even promote restoration from the train by boosting progress hormone, repairing broken proteins and decreasing irritation.
This interview merely touches on a small variety of highlights of the data present in “The Immunity Fix,” so to be taught extra, be sure you choose up a replica. To attach with DiNicolantonio and Land, see their web sites, DrJamesDinic.com and SiimLand.com. Each can be discovered on Twitter and Instagram by looking for DrJamesDinic (@drjamesdinic) and Siim Land.