Intermittent Fasting For COVID-19

[scoobydoo]

The effects of diurnal intermittent fasting on proinflammatory cytokine levels while controlling for sleep/wake pattern, meal composition and energy expenditure

"During DIF, there was a significant decrease in the levels of cytokines, particularly, IL-1β and IL-6, in most measurements compared to non-fasting BL. This reduction was more obvious during the FOR period. There were no significant changes in the circadian phase of the measured cytokines reflected by the acrophase of the measured variables during fasting (FOR and Ramadan) compared to non-fasting BL"

Peter Attia has been sharing lots of info on the immunological benefits of intermittent fasting, specifically for COVID-19 as it appears to lower blood levels of cytokines. I am curious if others have researched into this as well. I still very much am a believer in IF so long as calorie intake is sufficient.

 

[Hugh Johnson]

So IF causes immune suppression?

 

[RWilly]

Bacteria use viruses to cause stress in the host to access iron. Intermittent fasting does reduce the endotoxin load, likely because of reduced gut bacteria. Perhaps the reduced bacteria can reduce the virus response.

 

[Constatine]

I wouldn't fast for viral infections. Fasting typically increases host survival and lowers cfu count in bacteria infections but does the opposite in viral infections. There are quite a lot of studies showing that fasting is bad for viral infections. Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation

 

[LLight]

I wouldn't fast for viral infections. Fasting typically increases host survival and lowers cfu count in bacteria infections but does the opposite in viral infections. There are quite a lot of studies showing that fasting is bad for viral infections. Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation

Yeah but is it really a viral infection? Or put differently, is the virus really the issue?

And regarding fasting, I would advise you to do it dry, as it may improve the immune response.

Dehydration triggers ecdysone-mediated recognition-protein priming and elevated anti-bacterial immune responses in Drosophila Malpighian tubule renal cells

"
Background
Drosophila is a powerful model for the study of factors modulating innate immunity. This study examines the effect of water-loss dehydration on innate immune responsiveness in the Drosophila renal system (Malpighian tubules; MTs), and how this leads to elevated host defense and contributes to immunosenescence.

Results
A short period of desiccation-elevated peptidoglycan recognition protein-LC (PGRP-LC) expression in MTs, increased antimicrobial peptide (AMP) gene induction, and protected animals from bacterial infection. We show that desiccation increased ecdysone synthesis in MTs, while inhibition of ecdysone synthesis or ecdysone receptor expression, specifically within MTs, prevented induction of PGRP-LC and reduced protection from bacterial infection. Additionally, aged flies are constitutively water-stressed and have elevated levels of ecdysone and PGRP-LC. Conversely, adults aged at high relative humidity show less water loss and have reduced expression of PGRP-LC and AMPs.

Conclusions
The Drosophila renal system is an important contributor to host defense and can modulate immune responses in an organ autonomous manner, responding to environmental changes such as desiccation. Desiccation primes immune responsiveness by elevating PGRP-LC expression specifically in MTs. In response to desiccation, ecdysone is produced in MTs and acts in a paracrine fashion to increase PGRP-LC expression, immune responsiveness, and improve host defense. This activity of the renal system may contribute to the immunosenescence observed in Drosophila."

Maybe if it's combined with fasting, there is no immunosenescence: Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence
"In contrast, FMD cycles followed by refeeding are emerging as both an effective and feasible intervention with the potential for long-term and wide use. They are also emerging as potentially powerful interventions in the treatment of other age-related diseases and conditions including immunosenescence."

Similarity between the Marshall Protocol and dry fasting/dehydration:

Dry fasting/dehydration could help stimulate the immune system:

1. Dry fasting/dehydration may induce the secretion of oxytocin and vasopressin, two hormones involved in fluid retention/balance, which also seem to regulate the immune system or even have "antibiotic-like effects".
   
   
2. Dehydration may stimulate the production of the cathelicidin antimicrobial peptide (CAMP) in macrophages. This molecule has antibiotic properties and seems to be able to disrupt biofilms, structures that bacteria produce to escape the immune system.
   
   
3. NFAT5, a protein that tends to be upregulated, among other things, by hyperosmotic stress (that could be elicited by dehydration), seems to be involved in the proper targeting of bacteria by autophagy.
   
   
4. A deficiency of this same protein has been involved in autoimmune diseases (1, 2) which are, according to these publications and the Marshall protocol, nothing more than the consequences of immunodeficiency allowing pathogens to survive.
   
   
5. The NFAT5 protein itself seems to have antiviral properties against Coxsackievirus B3. This virus tries to deactivate the NFAT5 protein. I would not be surprised, knowing the importance of this protein, if other pathogens would try to suppress it too.
   
   
6. NFAT5 (also called TonEBP in the literature) seems to suppress the expression of the HO-1 enzyme in macrophages. HO-1 has a "well-established immunosuppressive activity". Interestingly, HO-1 inhibition could be a potential therapeutic strategy for metabolic disease.

Moreover, following dehydration (in mice, NFAT5 involved again), the CYP3A4 enzyme seems to be upregulated several folds in the liver (1, 2). This enzyme appears to be involved in the catabolism of vitamin D which "has multiple immunosuppressant properties".

____________________

The Marshall Protocol (see this video for an explanation about the theory) seems to be able to help people battle chronic inflammatory diseases, especially the so-called "autoimmune" diseases.

The theory of this professor is that following a first unresolved infection, intracellular pathogens decrease the potency of the immune system, for their own survival, by blocking the vitamin D receptor, such that subsequent infections are not as well dealt with, starting a vicious circle of increasing pathogens number and diversity inside cells and decreasing immune system's efficiency. These chronic infections could maintain chronic inflammation and metabolic abnormalities.

According to him, vitamin D cannot have the status of a vitamin, by definition, because it can be produced by the body and its level is controlled by feedback mechanisms.

The protocol involves:

1. trying to decrease vitamin D blood levels below 20ng/ml, the 25OHD3 form which "tempers bacterial-induced inflammation by slowing VDR activity", by abstaining from eating food containing vitamin D (especially fortified food or supplements),
   
   
2. taking a drug (Olmesartan) that activates the vitamin D receptor (VDR). The activation of the VDR "affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides". These are the same sort of peptides than the CAMP mentioned above,
   
   
3. taking low doses of antibiotics (minocycline) if needed.

One concept he develops is that every immunosuppressant substance (vitamin D, corticosteroids, fish oils, or immunosuppressive drugs) will provide relief in the short term, because it decreases the inflammation, but it will have negative effects in the long term by allowing pathogens to survive and even spread, making the disease worse. Note that autoimmune diseases are often "treated" with such substances.

Fighting these pathogens induces what is called immunopathologies (also known as “Jarisch-Herxheimer reaction”). In short, they are the bad side effects which are due to increased inflammation and fragments of dead pathogens (endotoxins or LPS), but they actually indicate that the immune system is fighting. They can often be interpreted as a flare-up of the disease.

NFAT5-sensitive Orai1 Expression and Store-Operated Ca 2+ Entry in Megakaryocytes

"The transcription factor nuclear factor of activated T cells 5 (NFAT5) is up-regulated in several clinical disorders, including dehydration."

"Platelets and megakaryocytes were isolated from wild-type mice with either access to water ad libitum or dehydration by 36 h of water deprivation."

"In the mice, dehydration increased NFAT5 and Orai1 protein abundance in megakaryocytes and NFAT5, Orai1, and Orai2 abundance in platelets. Dehydration further augmented the degranulation and integrin activation by thrombin and collagen-related peptide. In summary, NFAT5 is a powerful regulator of Orai1-expression and SOCE in megakaryocytes."

Emerging roles of store-operated Ca2+ entry through STIM and ORAI proteins in immunity, hemostasis and cancer

"The role of SOCE in immunity to infection is underlined by the severe, recurrent infections with viral, bacterial, and fungal pathogens affecting patients with mutations in ORAI1 and STIM1 genes that abolish SOCE.42,43 Patients are susceptible to chronic and recurrent viral infections, especially with herpes viruses such as cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus (HHV) 8.44-46 SOCE is impaired in cells of both the innate and adaptive immune system in these patients, and defective immune responses by both systems are likely to contribute to their immunodeficiency."

"NK cells are cytotoxic lymphocytes that are essential for immune responses against many viral infections and antitumor immunity. Intriguingly, ORAI1- and STIM1-deficient NK cells from patients showed impaired cytokine production, failed to exocytose cytotoxic granules and were unable to lyse tumor target cells when coincubated in vitro.46,51 Consistent with these findings, NK cells from Orai1KI/KI mice also showed reduced degranulation and cytotoxic function in vitro (SF, unpublished data)."

"Pathogens sequestered within phagosomes of macrophages and neutrophils are killed following fusion of phagosomes with lysosomes. The phagosomal production of reactive oxygen species (ROS) by NADPH oxidase is dependent on SOCE."

Platelets: essential components of the immune system

"Platelets interact with bacteria, viruses, fungi and protozoa and demonstrate anti-microbial functions."

"Upon contact with certain bacteria, platelets can become activated, aggregate and degranulate. Activated platelets release over 300 known secretory products including anti-microbial products (collectively known as platelet microbicidal proteins (PMPs))."

"Recently, a study demonstrated the expression of β defensin 1 in human platelets and its novel antibacterial activity [21]. It was observed that activated platelets surround Staphylococcus aureus and force the pathogens into clusters which reduce growth rate. Platelet-derived β defensin 1 not only impaired the growth of S. aureus, but also triggered neutrophil extracellular trap (NET) formation."

"In addition to the anti-microbial mechanisms as discussed above, platelets can internalize bacteria and viruses. Specifically, platelets have been shown to engulf S. aureus and human immunodeficiency virus (HIV) thus promoting pathogen clearance from blood stream and tissues [22]. In fact, platelets are capable of not only internalizing targets but also the killing of various internalized bacterial species including Escherichia coli and S. aureus [23, 24]. Whether this entitles platelets a potential phagocytic role needs further investigation. Furthermore, platelets generate and release hydrogen peroxide and other reactive oxygen species to mediate other anti-microbial effects in response to stimuli."

From my limited understanding, these elements suggest that dehydration could increase NFAT5 in immune cells (at least platelets here) and then ORAI1 and SOCE which seem to be necessary for an efficient immune response. Platelets are recognized more and more for being able to fight pathogens directly or influencing the other immune cells.

 

[Constatine]

Yeah but is it really a viral infection? Or put differently, is the virus really the issue?

And regarding fasting, I would advise you to do it dry, as it may improve the immune response.

I believe so. I have a much more traditional perspective when it comes to viruses. Of course there normally must be a degree of immune compromise for a virus to be realized, but in my mind viruses are a threat equal to bacteria in scale. It's important to liberally consume antiviral foods during viral infections.

 

[LLight]

Dry fasting may also help increasing nitric oxide in immune cells.

Very interesting connection being made here regarding this topic.

COVID-19 Mutations, Vaccines & Nitric Oxide - The Vitamin C Connection - EvolutaMente.it

 

[Tristan Loscha]

It increases weakness and decreases host-reserves for energy and Protein.
I wouldnt manipulate such a system,and starvation is associated with all worse outcomes.
Would recc against.

 

[Mhtro]

Dry fasting may also help increasing nitric oxide in immune cells.

Dry as in no water or any liquid? How long can you go without liquids and have the positive impact you describe?

 

[scoobydoo]

So IF causes immune suppression?

I'm not sure thats what it is stating. In fact I think just the opposite. cytokine lowering is not equivalent to lower immunity I don't think

 

[LLight]

Dry as in no water or any liquid? How long can you go without liquids and have the positive impact you describe?

16h without water increased NFAT5 in 2/3 of people and they were not fasting (protein restriction should also increase NFAT5)

I guess you could also eat low protein and drinking like 2 glasses a day only during a certain period of time (5 days for example) and to also have results.

The advantage of fasting is that you should produce ketones that could theoretically boost the production of antimicrobial peptides.

Additionally, when you are not drinking water, your body only has metabolic water at its disposal. Metabolic water is relatively depleted in deuterium, which could be helpful regarding the control of pathogens in the body.

Deuterium Depletion as a Possible New Strategy to Combat SARS-CoV-2

"Considering all available data on the effect of deuterium depletion on cell function and metabolism, and over 20 years’ experience with Vetera-DDW-25 deuterium-depleted veterinary medicinal anti-cancer product, which showed anti-viral effect of deuterium depletion in pets"

Mitochondrial deuterium depletion restrains prokaryote proliferation and virus hosting cellular events thus may alleviate the use of biologics

Burn (saturated) fat, create water, drink less and be immune?

 

[LLight]

There may be a link between COVID19 and tuberculosis:
Younger People Dying Of Covid19 Have Latent TB

And there could also be a link between Crohn's disease and tuberculosis (or other mycobacteria) as they seem to be hard to differentiate:
Distinguishing Tuberculosis and Crohn's Disease in Developing Countries: How Certain Can You Be of the Diagnosis?

This is interesting because NFAT5 seems to be downregulated in Crohn's disease:

NFAT5 expression is reduced in patients with inflammatory bowel disease
To determine whether the link between reduced NFAT5 expression and autoimmunity might be generalizable to other immune-mediated diseases, we examined NFAT5 mRNA expression in intestinal tissue biopsies from patients with inflammatory bowel disease (IBD). Crohn's disease (CD) and ulcerative colitis (UC), which together comprise IBD, are believed to result from an aberrant immune response to commensal gut microbes, leading to chronic intestinal inflammation. Compared to healthy controls, we observed that NFAT5 mRNA expression was significantly reduced in patients with active UC and CD (Fig. 7), raising the possibility that NFAT5 and other components of the osmoadaptation pathway may be dysregulated in IBD.​

 

[Constatine]

I'm not sure thats what it is stating. In fact I think just the opposite. cytokine lowering is not equivalent to lower immunity I don't think

Lower cytokine producing by itself is not necessarily a sign of immune suppression but lower cytokine production in response to infection is. Various cytokine should spike during infection.

 

[Tristan Loscha]

The effects of diurnal intermittent fasting on proinflammatory cytokine levels while controlling for sleep/wake pattern, meal composition and energy expenditure

"During DIF, there was a significant decrease in the levels of cytokines, particularly, IL-1β and IL-6, in most measurements compared to non-fasting BL. This reduction was more obvious during the FOR period. There were no significant changes in the circadian phase of the measured cytokines reflected by the acrophase of the measured variables during fasting (FOR and Ramadan) compared to non-fasting BL"

Peter Attia has been sharing lots of info on the immunological benefits of intermittent fasting, specifically for COVID-19 as it appears to lower blood levels of cytokines. I am curious if others have researched into this as well. I still very much am a believer in IF so long as calorie intake is sufficient.

I feel 'Peter Attia' is insane and wants the opposite of 'longevity' with this info-nugget made for you !!
2c..

 

[Hugh Johnson]

I would hypothesize that anti-inflammatory actions in response to infections might be useful for those eating a high omega-6 diet, because their body is already inflamed and being sick means the system is in serious overdrive. Less so for peatarians.

Even then, not eating is highly stressful and you would be better of taking aspiring or something. Of course, going for juices and other stuff that is less likely to feed gut bacteria could be prudent.