A small Merry Christmas message

Or Happy Holidays

First, and foremost, I want to wish all my readers a Merry Christmas or a Happy Holiday if you don’t celebrate Christmas.

Similar to last year’s message, I wish your holiday season to be cheerful, happy, and as much as you can try, positive. The world has changed as much as it did in 2023, and it is bound to change more in all directions in 2024, if there is a lesson I learned and took to heart this year, it is the world is what you make out of it. A quote from last year remains a habit you should pick up in 2025, if you haven’t.

You should take this time to reflect on the year, what you achieved, what you want to achieve in 2024, and what you can do better. As I shared in the past, I adhere to the “writing down your objectives, goals, and intent to the next year on paper”, and giving each of these a time frame, short, medium, and long-term, keeps me accountable and I often complete/achieve them faster than I have previously foreseen.

Writing things on paper has a significantly and substantially deeper impact on your brain and overall cognition than previously assumed by neurobiology, it is one of the reasons I sometimes recommend journaling, or reading scientific papers or articles of higher complexity and taking notes. When in doubt about anything, refer to your list back, it will consciously and subconsciously boost your drive towards achieving your goals.

In regards to the long-term consequences of Covid, the data is mostly crunched (the most time-consuming part usually) but I decided to try to keep the holiday spirits up, although mine isn’t this year =P, although such as Mozard, I am a vibes person. It is coming in the next few days. And so this isn’t completely empty or devoid of content.

Mozart was an “I follow the vibes” man

Weeks ago I covered a very recent paper on how BHB, an exogenous ketone, helps the body remove misfolded protein, and improve neurodegeneration, meaning what is supposed to be unreservable, actually is. To remain in the positive theme, BHB also enhances the effect of CAR-T cell cancer therapy, a new and often effective option to treat many forms of cancer.

Ketogenic Diet Enhances CAR-T Cancer Therapy

Researchers have found that a ketogenic diet boosts CAR T cell therapy effectiveness by enhancing tumor control and survival in mice with lymphoma. The key is beta-hydroxybutyrate (BHB), a metabolite produced during ketosis, which CAR T cells prefer as an energy source over glucose. Laboratory models showed that BHB supplementation led to complete cancer remission in most mice and enhanced CAR T cell expansion.

Translational studies in human samples confirmed that higher BHB levels correlate with better CAR T cell performance. This approach is now being tested in a Phase I clinical trial for lymphoma patients. If successful, this low-toxicity, cost-effective strategy could significantly improve cancer immunotherapy outcomes.

Key Facts:

• Ketogenic Boost: A ketogenic diet increased tumor control and survival in lymphoma-afflicted mice by enhancing CAR T cell efficacy.

• BHB Preference: CAR T cells thrive on beta-hydroxybutyrate (BHB), a metabolite from ketosis, outperforming glucose as a fuel source.

• Clinical Trials: A Phase I trial is testing BHB supplementation in lymphoma patients receiving CAR T therapy to validate these findings.

The reasons it works are a laundry list. You should read this paper but here is a glimpse of it.

Serum ALT↓, Serum HMGB1↓, Cleaved caspase3↓, IL-6 ↓, IFNγ↓, TNF-α↓, IL-1β↓, NLRP3↓, 4-HNE↓, Bcl-2↑, FOXO1↑, HO-1↑, LC3B↑

Serum ALT↓, Serum HMGB1↓, Cleaved caspase3↓, IL-6 ↓, IFNγ↓, TNF-α↓, IL-1β↓, NLRP3↓, 4-HNE↓, Bcl-2↑, FOXO1↑, HO-1↑, LC3B↑

Some of the changes ↓ (downregulated, cells produce less) are known to play large roles in cancer, so given the large list of gene, epigenetic, anti-inflammatory, and everything else BHB does, it is no surprise it is a versatile “anti-disease, longevity” molecule.

Here is another paper, recent too.

β-hydroxybutyrate alleviates neurological deficits by restoring glymphatic and inflammation after subarachnoid hemorrhage in mice

Results: Compared with the SAH group, BHB reinstated AQP4 polarization by upregulating SNTA1 protein to enhance the glymphatic system. According to RNA-seq, the different genes were primarily connected to microglia activation, astrocytes, and inflammation. Western blot and immunofluorescence further confirmed that the related inflammatory protein expression levels were upregulated. BHB attenuated neuroinflammation after SAH. Ultimately, it can mitigate the neurological deficits in SAH mice.

Conclusion: The study reveals a novel mechanism that BHB treatment mitigates neurologic impairment in SAH mice. We propose that BHB may play a neuroprotective effect by enhancing glymphatic system function and attenuating neuroinflammatory subarachnoid hemorrhage.

If you recall, the glymphatic system is the “brain disposal” system for bad proteins, your cells, and complex protein interactions “dissolve” the bad proteins, and the glymphatic system removes them. Failure of the glymphatic system, or efficiency loss (clearing less bad proteins) leads to accumulation. Thus, BHB improves glymphatic function, so not only does BHB “glue” itself to bad proteins, change them, and help the body break down, but also improves the clearance system used by the brain.

It will soon be researched and accepted that BHB acts as a universal metabolite on its own, with secondary, and perhaps tertiary pathways. A post-translational metabolite that can be “added” in other proteins to exert profound changes.

Hope everyone has a great day today and tomorrow (Brazilians often celebrate Eve more than the day itself lol…)

I appreciate and I am grateful for everyone who chose to support me this year and everyone who has supported me since the start.