Nicotinamide and probiotics for Covid recovery

And the two pandemics that never were

I guess we should start the next half of the month with a more uplifting tone because it will get darker again. I will address the most important studies first, rather than 2 self-indulgent pieces of news.

If you have been following me for a few years, or even if you are a recent follower, around one year, you will be aware that among the many points I consistently and persistently brought up is NAD+. NAD+ can be simplified as “cell fuel”, cells will continuously produce NAD+ because it also acts as a necessary step towards other functions, not just “cell fuel”.

One of the hallmarks of SARS-CoV-2 is the rather drastic, systemic depletion of NAD+. Dizziness before or while infected ? A decent chance it is NAD depletion. Brain fog ? Yep. Many symptoms can be tied to NAD depletion and the complications that follow, after all, the collapse of every complex system is low energy, or expensive energy, and even at a molecular level, that remains true.

Tryptophan goes through a complex process and gets broken down into NAD, and this process is ruled over by the Kynurenine Pathway. The virus, the Spike Protein, other viral infections, latent virus reactivation, and stress will also deplete your body out of NAD (called NAD+ pool), and if you throw systemic inflammation into the mix, you get the immuno-toxic side of the Kynurenine Pathway.

The importance of (proper) Tryptophan Metabolism

Kynurenine Pathway and SARS-CoV-2

I was suggesting supplementing with different forms of Vitamin B3 since early 2021, with a “protocol” being one of the first articles published in this Substack. Over time science did catch up.

Things Hidden Since the Splicing of SARS 2 S protein (part 2)

Treatment of SARS-CoV-2-induced pneumonia with NAD+ and NMN

Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19

Every patient in this study was infected by either Alpha or Delta, two of the “nastiest” strains before Omicron, and everyone was unvaccinated. I have stated multiple times that vaccine-injured have a higher innate need for NAD+, degree of injury is not a factor, since NAD+ is particularly important and upstream.

The author of this paper raises a great point, SARS-CoV-2 is known to damage the gut barrier, making the gut more permeable, impacting the microbiome constitution, shifting the abundance of the wrong microbes, lowering the good ones, and affecting ACE2 expression.

ACE2 and healthy gut barrier integrity are really important for absorbing nutrients, including components needed for Vitamin B3 production or absorption, like tryptophan. When both the gut barrier and ACE2 function are disrupted by infection, it can impair tryptophan absorption and alter its metabolism, which in turn can contribute to more inflammation and immune dysfunction in the body.

This study was a double-blind, randomized, placebo-controlled trial involving 900 patients with mild-to-moderate Covid-19. They used a specific Nicotinamide formulation that wasn't just a standard pill. It combined a conventional, immediate-release form with a new type designed to release later, specifically in the small intestine and colon. You can replicate this delayed released by buying enteric coated vitamins =).

The results are nuanced, after all, even drugs are not magic pills, thus, supplementation suffers a more nuanced and individualized effect. For the most part, supplementation is often aimed at accelerating recovery and fueling the body with what it needs “more”.

Authors measure effectiveness by improvement of symptoms and how quickly patients taking Nicotinamide go back to normal activities, and that is exactly what the data here shows, faster recovery. Fatigue among the patients here was already mild, so fatigue improvement shouldn’t be taken too heavily.

As a simplified rule of thumb, mild to moderate infections will lead to lower rates of Long Covid, albeit I would disagree over a long enough timeline. Thus, Long Covid patients were already in low numbers in this trial, but the authors found that the nicotinamide group had lower Long Covid scores at 6 months compared to the placebo.

The reason I found this study interesting enough to share was the microbiome effects, besides the mounting trial of evidence that simple and cheap interventions can speed up recovery at the very least. This very complicated measurements and presentation of multiple highly significant metabolic pathways in the body.

A better way to explain the information presented here is that there's a consistent trend demonstrated where several key microbial metabolic pathways are significantly altered between the groups of patients. These include pathways involved in the biosynthesis (creation) of essential amino acids such as tryptophan, lysine, and methionine, the production of certain Menaquinols (forms of Vitamin K2), and the microbial NAD+ salvage pathway (that's the way bacteria recycle NAD+ precursors, not your body’s Kynurenine pathway using tryptophan).

Unlike other studies that often focus on changes in the types or abundance of specific microbes (compositional shifts), this research highlights a functional shift, changes in the microbial community's capacity to perform certain metabolic tasks. This gives a clearer perspective on the metabolic impact of mild-to-moderate infections at the microbiome level, giving insight into the metabolic level.

Nicotinamide intervention (by their data) prevents or reduces the compensatory increase in the biosynthesis and salvage pathways observed here, and when compared Nicotinamide group with placebo and other Covid-infected groups, and healthy individuals, the Nicotinamide group will often present a microbiome and its metabolic-related pathways much closer to those of healthy individuals.

By having sufficient NAD+ reserves (NAD+ pool) by supplementing with nicotinamide, it helps the body replenish NAD+ and directly modulates tryptophan metabolism, since you have another source for NAD, this likely alleviates all the cellular and metabolic stress signals that drive the microbes to shift the metabolism of many amino acids.

Sufficient NAD+ thus leads to better amino acid availability by improving a diverse range of metabolic pathways, avoiding the body from compensatory mechanisms and salvage pathways (and we have many of these…gives me a headache really). And since we are talking about trials, the microbiome, and supplementation.

Marked reduction of SARS-CoV-2 infection and improved recovery following supplementation with a probiotic mix of four strains and two strains of Bifidobacterium breve in hamsters

Only a few studies have shown that certain probiotics have beneficial effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, two strains of Bifidobacterium breve, CNCM I-5644 and CNCM I-5979, selected for their in vitro immunomodulatory properties demonstrated in a screening of 20 strains and a mixture of 4 probiotic strains selected based on its immunomodulatory and antiviral properties were evaluated in a hamster model of SARS-CoV-2 infection. Supplementation with these probiotics (7 days before plus 7 days after infection) reduced SARS-CoV-2 infection with a significantly reduced viral load in the upper respiratory tract and lungs and improved weight recovery. Probiotics also counteracted the increase in inflammatory markers and intestinal permeability. The impact of these probiotics was independent of microbiota composition and short-chain fatty acid production. Overall, these data suggest that the probiotics tested, in particular the mix containing Bifidobacterium longum LA101, Lactobacillus helveticus LA102, Lactococcus lactis LA103, and Streptococcus thermophilus LA104, can facilitate recovery from SARS-CoV-2 infection (as shown by weight regain in infected hamsters) by reducing viral load and inflammation.

This is a harmster study, but in case you haven’t read me for over 3 years, or are new to scientific research, harmster studies often are a decent signal to the effects in humans, in fact, many early hamster and mice studies were proved time, and time again in humans on a later date, especially in regards to SARS-CoV-2.

Here, the authors found that supplementation with a specific mix of probiotics induced significant changes in the immune system, had antiviral effects, and improved recovery from the infection. Specific strains of microbes, especially as a supplement, have significant and distinct effects in the body, and here, specific strains improved the infection and recovery markers.

Special interest should be given to the fact that probiotic supplementation counteracts the inflammation, but especially intestinal permeability, which is a hallmark of long-term damage from the virus. Even mild infections affect the gut, but we lack evidence on the degree the gut barrier is affected and how long recover to baseline takes.

Given that any real-world metric you want to use, such as Long Covid, Long vaccine, Vaccine injury, moderate to severe infection, all share this similar trend (dysbiosis, damage to the gut at one point or another), help in this matter is welcomed.

I am yet to test Akkermansia Muciniphila, which to me is likely the most important microbe to supplement at any point of a SARS-CoV-2 infection, but especially after, but I have tested Lactobacillus Reuteri and had significant benefits from it. Many Lact strains are very beneficial.


Last in the science part of this article.

Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial

This is a small but human trial with a decent design (methods section), with the goal of assessing the effects of supplementing Vitamin D, and VitD+NAC in older adults, with the primary focus on immunosenescence. Immunosenescence is a hallmark of aging, when the immune system gradually deteriorates, immune defenses slow down, and there are significant shifts in immune populations, thus leading to old-age diseases and a higher propensity for infections of all kinds.

Vitamin D is quintessential to our lives, and older people by age alone have a harder time producing appropriate levels of one of the most important systemic hormones in the body, another hallmark of older age is the constant “deficiency”, or better yet, depenecy on exogenous antioxidants, when you are older your body doesn’t have enough antioxidants, especially its master antioxidant, Glutathione.

Supplementation with 5.000 IU of Vitamin D alone, and this dosage of VitD + 600 mg of NAC, daily, for 8 weeks had a significant antiinflammatory, immuno-modulatory effect on the senescence-related genes and markers. Vitamin D alone had this effect, but this higher dosage of Vitamin D administered together with NAC had synergy, with NAC potentiating VitD effects on the senescence.

This isn’t exactly news for most of my readers, but it is good to have evidence to point any healthcare provider, or doctor, family members towards, as it is much easier to understand “They tested this in people and it worked”, rather than the usual cutting-edge research.

The Pandemics that never were

To the self-indulgent part. As someone who followed extremely closely the avian flu pandemic, from its earliest, forgotten and ignored signals to the quasi-propaganda war of recent months, it still remains of interest as a matter of curiosity and track record. Thus, more good news.

Cases of avian flu have been declining both in animals but also in humans, and most cases in humans, if not all, are related to animal exposure. In recent months I shared the most up-to-date evidence on avian flu and its dynamics in animals and humans, culminating in one paper where the authors found we have cross-reactive immunity, meaning other flu viruses infecting us, and this protects us from the brunt and severity of this novel virus.

The only real way Avian Flu would come to cause a human pandemic would be with a human hand, and I guess this early assessment of mine has proved to be true. The second self-indulgent news.

More Monkeypox "breakthrough" cases

Monkeypox may have undergone 'accelerated evolution,' scientists say

I covered MonkeyPox throughout 2022, as it suddenly popped up in a pocket in Europe, and it spread elsewhere, although its endemicity was always contained within a specific group. The vaccine was a failure from the get-go, with vaccinated individuals getting infected as soon as they got vaccinated. As a Lol, lmao even moment.

T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination

To the surprise of no one but a few, the authors of this paper tested the immune response of the MonkeyPox vaccine, and to the infection, uncovering the obvious. While the MonkeyPox vaccine induces a decent immune response to the metrics used by the researcher, T-cells from infected patients had greater cytotoxicity, migratory potential, and TCR clonal expansion.

Meaning the most protective measure against a MonkeyPox infection is getting infected, not vaccinated, with a much stronger and broader immunity overall. It is still a mystery how MonkeyPox went from a non-issue in the entire planet, to a measurable and trackable problem……………

I may write something else, simpler, in the science department in the next few days, rather than my usual.


Consider becoming a supporter, it helps my work here, and if you are one, thank you !