"Fixing" T-Cell exhaustion

A short and simplfied 'guide'

As an opening statement, this will be less “sciencey”, it is a short article aimed more at being helpful rather than “connecting dots” as my usual ones are. I decided to write this on the spur of the moment, although the research efforts have been there ever since I came to research and connect the dots about T-Cell exhaustion. Particularly, I am not very fond of increasingly cutting-edge treatments that are :

• Too expensive

• Very hard to scale given the complexity of its production pipeline

• Even if the molecules are “easier” to produce, half the planet lacks the knowledge and industrial base to do it

So I now present you a few approaches towards T-Cell exhaustion. As a “FYI,” this isn’t much applicable to most, since we are not experiencing a collapse of T-Cell function at the global level, but the information is valuable to be shared, especially pertinent to people with chronic viral infections, Long Covid, Cancer, etc.

I have argued for some time that many if not most human diseases and their long-term effects are often byproducts of energy efficiency collapse when your body and cells can’t properly produce bioenergy. Our immune system would not be different, and I have written for a while about how specific immune cells have “preferred” metabolisms, with the biggest “culprit” among all for variance and bioenergetic failure being glycolysis. Everything loves sugar.

Source

By mere coincidence, this paper proposes and demonstrates one of my arguments in my T-Cell Exhaustion article, that TEx occurs from excessive ROS (cell rust in my simplified terms) which directly affects mitochondrial function. The T-Cell exhaustion goes through a similar change in metabolism as cancer cells, in fact, cancer is one of the primary methods and models to study TEx, called “The Warburg Effect” where the cells just go towards high rates of glycolysis (breaking down sugars), so fast it creates “cell rust”.

Nicotinamide, another form of Vitamin B3 which we could call “Niacin sister” is able to both prevent and reverse TEx, it directly inhibits the expression of inhibitory receptors, and it reverted the inhibitory effects of TEx, affecting the production of IL-2, IFN-Gamma and TNF-Alpha, the proteins that you need to fight a whole host of pathogens. It also reversed the expression of TIM3 and LAG3 in TEx cells, and if you recall these proteins are responsible for the dysfunction in the exhausted cells.

The most remarkable finding was that Nicotinamide was able to help both CD4+ and CD8+ T cells differentiate in both TEM (effector) and TEMRA (memory) cells. If you don’t remember, this is the specific cells that are dysfunctional in a subset of Long Covid patients, among a few other conditions.

Before delving further into other methods to deal with TEx, Nicotinamide as a supplement has a myriad of other uses, such as helping treat depression, and depending on the root cause, anxiety. It is worth reading more about its other uses, such as inhibiting mycobacterium tuberculosis replication.

Nicotinamide Riboside (NR) is one of the closer steps in the NAD+ pathway, and it has been widely researched in recent years for this property alone, but lately, the main interest has been in its possible “anti-aging” effects. By being part of the pathway responsible for energy metabolism, NR has positive effects on TEx in a sepsis model, as Nicotinamide, NR also had positive effects on CD4 and CD8 cells, and remarkably it increase both Th1 and Th2 cells yet brought them to a balance.

A skewed ratio between T helper cells is one of the hallmarks of many inflammatory and allergic diseases and states. NR also lowered the bacterial load and organ damage in this septic model.

Arguably one of the best “cures” for NAD+ dysfunction or systemic deficiency is Niacin, one of the most studied forms of Vitamin B3 (all supplements discussed so far are a form of Vitamin B3).

Niacin Cures Systemic NAD⁺ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy

Highlights

• Mitochondrial myopathy patients have NAD⁺ deficiency in muscle and blood

• Niacin is an efficient NAD⁺ booster in humans

• Niacin improves muscle strength and fatty liver in mitochondrial myopathy

• Niacin boosts muscle mitochondrial biogenesis and respiratory chain activity in humans

Niacin has too many uses, and innumerable amount of papers published on its many uses, it was primarily used to lower cholesterol, but it has an unbelievable amount of other positive effects on our bodies, especially for anyone with persistent inflammation, diabetes, and other modern, often metabolic in nature, diseases. Not the first, won’t be the last time I suggest its use, but there is a caveat many people miss.

First, you must only use Niacin Flush, the non-flush type literally does only one thing for you. Liver damage. Second and significantly, the consumption of Niacin close to carbohydrates can induce insulin resistance long-term. Just space the consumption of Niacin if you are going to use it.

One significant dynamic in SARS-CoV-2 derived T-Cell dysfunction is their impaired ketogenesis. And a very low carbohydrate diet directly enhances T-Cell immunity and immune function through metabolic reprogramming. By adding ketone bodies such as BHB these researchers were able to both rescue and potentiate dysfunction CD8 cells from severe Covid-19 patients.

In the odd case you were not aware, yes, you can easily buy and use ketones as a supplement, aiding in researching a ketogenic state, or helping your metabolism go into deeper ketosis.

Last but not least, as a “last resort” because of its price point. Thymalin and Thymogen.

The many wonders of Peptides

I am a huge proponent of the use of peptides to fix a myriad of issues, I have extensively used some myself to heal from conditions modern medicine described as “unfixable”. But since 2020, there has been quite a shift in the global peptide markets, both in the US and in China, the Chinese government cracked down on all labs producing peptides, and a significant portion of the supply went offline.

Read about both peptides, and decide if it is for you or not, but I advise you to be careful and go slow. TEx isn’t merely a dysfunctional state, but a compensatory one, your body was or is attempting to mitigate the damage from something else. This commentary is in regard to immune-modulating peptides such as Thymalin and Thymogen.

Given the impactful role cellular metabolism, especially glycolysis plays on T-Cell Exhaustion, both Berberine and Metformin play an indirect role in modulating the metabolism and immune cells in a very positive manner. Such as the decline in bioenergetic seeing in tuberculosis, can be rescued and CD8 reinvigorated by Metformin. Metformin can also reduce CD4 T cell exhaustion in HIV-infected adults in suppressive therapy. Similar potentiating CD8 effect in cancer.

I hope this is helpful to some people on their road to recovery.

If you chose to become a supporter of my work, thank you, and thank you for reading.