Positive effects of the Ketogenic diet on the brain

And the pointless effort of human influenza vaccination

I meant to send an e-mail yesterday but decided to just help my mother cook, and do stuff around the house so she could have a chill day. But as they say, better late than never.

A late Happy Mother’s Day to all moms that read this substack.

Stole this from a friend this substack

Before we delve into the ketogenic diet paper I referred to in the last article, first a few pieces of information, it sounds contrived to mention these now, but I rather take this out of the way now, rather than later. A ketogenic or low-carbohydrate diet is for most people, highly diuretic, in simple terms you will pee a lot.

Water intake isn’t usually a problem for 99% of people adhering to the diet, but some experience certain “side-effects” that are not pleasant, among them the “keto flu”. The majority of the Western population has a poor salt intake, poor magnesium intake, and most certainly poor potassium intake, to avoid these side effects if you decide to try this dietary change, you should add more salt to your diet and electrolytes, with special attention to magnesium and potassium.

The second part, as I discussed with some of the most brilliant doctors in their fields, it doesn’t matter much how you achieve the low-carb part of the equation, as long as you limit your carbohydrate intake. Some people, me being a perfect example, can’t handle high amounts of fat, even if I break it down throughout the day, so the better strategy is a low-carb high-protein diet (I will also write something here about high-protein diets and kidney function). Find what works for you.

Lastly, a non-intentional byproduct of any diet that restricts carbohydrate intake is weight-loss, but unmanaged weight loss and drastically cutting carbohydrates can lead to long-term problems. The more fat you possess, the less drastic your carbohydrate intake should be. If you are obese, or morbidly obese your “low-carb diet” will look like a high-carb diet for strictly keto “bros”. Start with small cuts, and go from there, this applies to anyone, but obese/morbidly obese should never drastically cut the carbs, ever, you will lose the most precious of resources. Lean mass.

I personally adhere to carb cycling. Meaning a strictly low-carb diet for X days (6 in my case) with 1 day where I am carb-free, and when I say free, I mean it. Also, a low-carb diet drastically changes for each person, if you sit on your ass and do some mild exercise, even if daily, 50-130 grams of carb is “low-carb”. My friends from Special Forces can maintain ketosis at 250-300 grams of carbs, because of the high level of activity. The more effort you put into exercise and fitness (especially functional strength) the more carbohydrate freedom you have. Unrealistic for most people, but I rather leave this tidbit of information here.

One high-carbohydrate meal (like a pasta dish) in the middle of your X days won’t ruin your diet, it won’t throw you out of ketosis. That is a myth. Multiple high-carb meals definitely will.

The ketogenic diet has been one of the major components of my “how to heal yourself from Covid) series of posts. The Part 3 isn’t overly big and it is worth a look. Ketosis is also highly important for immune function. The articles below are but a few of the many times I directly mentioned the ketogenic diet or BHB.

Things Hidden Since the Splicing of SARS 2 S protein (part 3)

Impaired Ketogenesis ties metabolism to T cell dysfunction in COVID-19

Spike in the brain II - How to deal with NETs

Now to the main reason, we are here today. FYI, the entire paper is worth reading, especially the Introduction section since they cite a lot of interesting evidence in regards to KD (Ketogenic Diet) and many other conditions.

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

Conclusions: KD can exert substantial neuroprotective effects via multiple molecular mechanisms in various neurodegenerative and psychiatric pathological states. Large, long-term, randomized, double-blind, controlled clinical trials with a prospective design are strongly recommended to delineate whether KD may attenuate or even treat neurodegenerative and psychiatric disease development, progression, and symptomatology.

Molecular mechanisms through which KD can exert neuroprotective effects in vitro and in vivo (adenosine trisphosphate, ATP; reactive oxygen species, ROS; gamma-amino butyric acid, GABA; peroxisome proliferator activated receptor, PPAR; mammalian target of rapamycin, mTOR; 5′ adenosine monophosphate-activated protein, AMPK; interleukin, IL; brain-derived neurotrophic factor, BDNF; transforming growth factor beta, TGF-β; inducible nitric oxide synthase, iNOS; cycloogygenase-2, COX-2; tumor necrosis factor alpha, TNF-α; nuclear factor kappa B, NF-κB; uncoupling proteins, UCPs; increase, ↑; decrease, ↓).

For our intents and purposes, I will refer to the most meaningful mechanisms by which KD helps against neurodegeneration and psychiatric diseases, because both hold a massive correlation with SARS-CoV-2 and mRNA pathways we have covered so far. BHB, sometimes referred to as BHBA (Beta-Hydroxybutyrate Acid) is the most abundant “byproduct” of the KD. In microglial cells (immune cells of the brail), BHB can shift them towards an anti-inflammatory state and decrease migration of these cells after LPS stimulation, this is incredibly important because activation, especially persistent, in the brain is one of the hallmarks of many neurodegenerative states (including Long Covid), it also significantly lower the production of IL-17, the biggest contributor to inflammatory diseases and the main culprit into shifting your immune system towards Th17.

All the effects described in the paragraph above could be ascribed to the effect BHB has on the nucleotide-binding domain and leucine-rich repeat-P3 (NLRP3), an inflammasome, and as the name implies its role in immune regulation and inflammatory signaling, it is fairly “upstream” in the physiological cascade effects we covered a few times here, and by inhibiting such important part it reduces the amount of other potent inflammatory proteins use was IL-1Beta nad Caspase-1 (caspase-1 participates into multiple functions in inflammatory responses), BHB also lower ROS, lowers cellular mortality. And by directly increasing NADH oxidation (cells making energy), and lowering the inflammatory burden it increases glutathione synthesis, which is one of the most important aspects of neurodegenerative and inflammatory diseases.

As a potent suppressor of IL-6 and TNF-Alpha, both responsible for much of the damage one can observe in a myriad of diseases, from acute to chronic infections, and by modulating the specific proteins described above, BHB can regulate dopamine neurons through facilitating the GPR109A signaling pathway (Niacin uses the same receptor, and achieves similar effects).

Another positive effect of the KD (observable only after weeks under the diet) was the attenuation of Amyloid beta 40 and 42 (the most toxic parts of your brain), each section of the brain had a different time for the KD to induce this protective effect. Since aberrant, out-of-control glucose metabolism is present even in the early stages of cognitive impairment, the KD already has a positive impact from the get-go.

Source

KD for 16 weeks was also found to regulate the gut microbiota in young, healthy mice, and ketone bodies’ release was associated with the gut microbiota modifications [40]. KD significantly increased cerebral blood flow (CBF) and P-glycoprotein passages on the blood-brain barrier (BBB) to accelerate Aβ clearance [40]. These neurovascular enhancements were related to decreased mechanistic target of rapamycin (mTOR) and increased endothelial NOS (eNOS) protein expression levels. Moreover, KD raised the relative plethora of potential favorable gut microbiomes (Akkermansia muciniphila and Lactobacillus) and diminished that of potential pro-inflammatory taxa (Desulfovibrio and Turicibacter) [40].

Dysfunctional production of eNOS is a hallmark in many post-Covid (or post-mRNA exposure) damage, overly represented among many Long Covid patients, so merely shifting to a KD and improving the production/expression already promotes better circulatory function.

The gut microbiome modulation is one of the most significant from the SARS-CoV-2, Akkermansia is displaced by Omicron even months after a mild infection, and it is responsible for modulating many important metabolic and immunologic pathways inside our bodies. And Desulfovibrio was mentioned in this Substack recently, responsible for neurodegeneration, so diminishing the presence and bringing it to balance is another positive effect. Below is an overview of the impacts of the KD in many different conditions.

A big part of my observations of the myriad of adverse effects of the Spike Protein was, and still is the Kynurenine Pathway. Supplementing with BHB (referred to as Exogenous Ketones or Exogenous BHB) is a way to accelerate ketosis and its effects, with everything described above being a perfect example. Supplementing with Exogenous BHB may help preserve lean mass. But one remarkable effect of the Ketogenic diet or perhaps adding BHB with less carb intake is…

In conclusion, using a combined untargeted/targeted metabolomics strategy, we showed that the TRP degradation pathway, which includes the metabolism of KYN, is a target of the KD and mild caloric restriction. Considering the indecisive results of this study, modulation of this pathway may or may not be involved in the beneficial effects exerted by the KD and mild caloric restriction in the treatment of epilepsy and neurodegenerative diseases.

Source

Changes in tryptophan and kynurenine pathway metabolites in the blood of children treated with ketogenic diet for refractory epilepsy

• The kynurenic pathway may be modulated by ketogenic diets (KDs).

• KDs affect plasma levels of kynurenines in refractory epileptic patients.

• Specifically tryptophan and kynurenine levels decrease, kynurenic acid levels increase, while levels of 3-hydroxykynurenine remain unchanged.

• Increases in plasma levels of kynurenic acid correlate with greater seizure reduction.

I hope with this somewhat decent overview of the Ketogenic diet and some of its positive effects, it may work as an introduction and fuel to the consideration of many people on either trying the diet or delving further. As one of the leading experts in ketone research said “Perhaps we modern humans are all ketone deficient and as a byproduct of such state, the ketogenic diet possesses so many positive effects on our physiology.”

Last, one of my years-long crusades has been the futile attempt on vaccinating against influenza, with much discussion engaged to little avail. We finally have decent evidence that vaccinating against influenza is a pointless effort. Protection wanes fast, and we are basically driving viral evolution.

Do you know what really protects against influenza infection ? The ketogenic diet. Who would have thought that a glucose-hungry virus, would be affected by depriving the virus of that fuel.

This one for a dear friend, Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health. The ketones directly and positively impacts mitochondrial function and health.

Thank you for your support here or anyone who used Kofi, it does help !