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Intracellular NAD+ Testing & Optimization: Supporting Synthesis Pathways



Today, I want to discuss intracellular NAD+ testing: I will be doing a blood test to determine my levels, and later, after a few weeks, I'll retest and share the results of my optimization protocol. I'm genuinely excited about this because I enjoy applying my research through self-experimentation, and any improvement in NAD+ levels is beneficial. But with that said, let's get into the research.


Now, you've likely heard about NAD+ and its significance for energy, longevity, and more. However, understanding how it functions can aid us in exploring ways to boost our levels naturally, rather than relying solely on external NAD+ therapies (IVs, injections, patches, etc). Of course, treatments like NAD+ IVs, patches, and injections have their place, but today, I aim to focus on compounds, supplements, nutrients, or lifestyle factors that enhance our body's ability to regenerate or synthesize NAD+ internally.


So, why is NAD+ crucial? NAD+ is integral to various cellular processes, including repairing damaged DNA, eliminating aging (senescent) cells, supporting mitochondrial function, regulating sleep and immune response, and reducing inflammation and free radicals. It serves as a catalyst for over 500 enzymes, notably those involved in cellular energy production (ATP). Therefore, let's delve into its role in energy metabolism.


When we consume carbohydrates, they are broken down into glucose, which enters the cell, initiating glycolysis. Glycolysis relies on enzymes like glyceraldehyde 3-phosphate dehydrogenase, which necessitates NAD+ for continued function. Similarly, during the Krebs cycle in the mitochondria, NAD+ is utilized by various enzymes to facilitate energy production. Ultimately, NADH generated in these processes fuels the electron transport chain, leading to ATP synthesis. Maintaining the balance between NAD+ and NADH is critical for efficient energy production. Disruptions in this balance, such as those caused by environmental toxins, drugs, or reactive oxygen species (ROS), can impede the electron transport chain, leading to decreased NAD+ levels and energy production.


To counteract such disruptions, we can explore pathways for increasing NAD+ levels. Firstly, the de novo synthesis pathway relies on tryptophan, obtained from dietary protein, to produce NAD+. A study demonstrated that even a short-term low-protein diet can impair this pathway (and create metabolic dysfunction), emphasizing the importance of adequate protein intake.


Another pathway, the Preiss-Handler Pathway, utilizes nicotinic acid (a form of vitamin B3) to synthesize NAD+. Supplementation with niacin has shown promising results in increasing NAD+ levels, enhancing muscle strength, and promoting mitochondrial biogenesis.


Lastly, the salvage pathway involves recycling nicotinamide, a breakdown product of NAD+, back into NAD+. Supporting this pathway can be achieved through supplementation with nicotinamide mononucleotide (NMN) or nicotinamide riboside (which can be converted into NMN).


In addition to these pathways, inhibiting the enzyme CD38, which consumes NAD+, can help preserve NAD+ levels. Compounds like apigenin and quercetin can inhibit CD38 activity: Quercetin is a flavonoid found in various fruits and vegetables while Apigenin is another flavonoid found in parsley, celery, and chamomile tea.


Study:

Hu G, Ling C, Chi L, Thind MK, Furse S, Koulman A, Swann JR, Lee D, Calon MM, Bourdon C, Versloot CJ, Bakker BM, Gonzales GB, Kim PK, Bandsma RHJ. The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction. Nat Commun. 2022 Dec 8;13(1):7576. doi: 10.1038/s41467-022-35317-y. PMID: 36481684; PMCID: PMC9732354.


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