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Deuterium/heavy isotopes (eg D2O, C13) and longevity thread


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https://www.linkedin.com/pulse/deuterium-secret-yucatán-doris-loh/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108472/

I drank deuterated water two days ago (only a little) but it gave me some ideas, and it's possible deuterium increases the dof that the brain can express itself in its proteins too (if the body knows how to deal with deuterated compounds) => a possible route to improving memory with deuterium (esp b/c deuterium is *harder to clear/change* than normal hydrogen). [note this is SUPER-speculative but I'm putting it out there bc it's falsifiable)

[1400 British pound/L...]

Also deuterated compounds (and C13) are harder to remove from the body, so maybe if you gave a lot of C13 during reprogramming (or some other plastic influence like a psychoplastogen or tFUS), it would stay for longer => stronger argument for its cost effectiveness despite expense.

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"In addition, food prepared from animal sources tends to have much higher nitrogen‐15 content compared with food from plant sources, as observed in infant formulas and whole animals 9, 15. This suggests that the position in the food chain/web also has an impact on heavy isotope content

"much" higher?? Does this ALSO mean that heavy isotopes will STAY in the body once ingested?

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https://www.fightaging.org/archives/2016/09/a-review-of-heavy-isotopes-and-slowed-aging

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I could also imagine differences in SOME protein-protein interactions or protein-ligand interactions (b/c they do change the geometry *enough* and small changes in this can have very large effects downstream), especially ones that result in signal transduction cascades. It may slow them down a bit, but slowing them down could be important for *getting other things* to properly multiplex [TESTABLE SPECULATION].

[if a chemical has multiple degradation pathways, it can shift the balance away from some reaction byproducts, maybe especially including ones broken down by MAO-A]

Deuterium gives an additional degree of freedom if you want to achieve extremely precise control over atoms

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There's also "deuterium depleted water" [https://www.linkedin.com/pulse/deuterium-quantum-paradox-light-water-magnetism-doris-loh/ ] which is the OPPOSITE of what we should expect for longevity... andhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746303/ also says the opposite.

HOW TO MEASURE: https://www.linkedin.com/pulse/deuterium-101-chapter-1-measuring-doris-loh/

But https://www.linkedin.com/pulse/deuterium-secret-yucatán-doris-loh/ is mildly worth reading

I don't believe these as much b/c there is already so little deuterium in the body *anyways* - the data for pro-deuterium kinetic isotope effect is more compelling and is cited by fightaging AND michael snyder is one of the authors for this

 

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Deuterated Vitamin A (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048682/), deuterated dopamine/L-DOPA (against Parkinson's - https://www.michaeljfox.org/grant/enhanced-dopamine-availability-prolonged-activity-and-improved-dyskinesia-profile-after), deuterated DMT (Cybin), deuterated psilocybin are ALL in clinical trials

Deuterated cannabinoids - https://patents.google.com/patent/US5036014A/en

Structure

Reaction

Therapeutic indication or use (mechanism of action)

Advantage given by deuterium incorporation

Highlighted in reference

41573_2023_703_Taba_HTML.pngd9-caffeine

CYP1A2-mediated amide and amine N-dealkylation

Apnoea of prematurity in infants; pain medications associated with analgesic agents (adenosine receptor antagonist)

Increase in PK parameters (longer t½, higher AUC); slower oral absorption

35,36,37,38,39,40

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https://www.nature.com/articles/s41573-023-00703-8

what is the easiest imaging method (eg fNIRS/MRI/raman) to detect for deuterium enrichment in an organism over time? 

=> Yale has a lab: Deuterium metabolic imaging (DMI) lab:https://medicine.yale.edu/lab/dmi/faculty-researchers/

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Depending on how heavy isotopes are introduced, in general they should retard catabolic reactions but produce much milder effects on the anabolic reactions (see Fig. Fig.33 for an example of deuterium and hydrogen). Therefore, it is more likely that the observed heavy isotope decline derives from internal partitioning, a notion that is supported by observation that the heavy isotope content declines in the same metabolites found in both the cytosol and media during yeast aging, as demonstrated for glutamine 5.

Promoting longevity and health by heavy isotope supplementation

Before our observation of heavy isotope decline during organismal aging, deuterium‐bearing heavy water has been shown to promote longevity or improve certain health aspects in several organisms, including fruit flies, rodents, and humans 19, 20, 29, 37, 38. In fruit flies, transient exposure to heavy water at juvenile stages extends lifespan, and the exposure does not affect the health and reproduction 19

 

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The proposed heuristic model shows that when the concentration of D is lower than the normal value of ≈150 ppm, the oxidative stress increases, slowing down cell proliferation. However, when D concentration becomes higher than normal, cell growth is promoted through inhibition of ROS production. The growth acceleration effect seems to peak in a broad range of deuterium concentrations between 250 and 500 ppm, with ≈350 ppm being the center of that interval. Incidentally or not, this is the value predicted for maximum growth acceleration by the isotopic resonance paradigm (55, 56), which is supported by several previous observations (13, 14). Because the growth acceleration effect at 350 ppm is nearly halved when the resonance conditions are destroyed, at least part of the effect must be because of the isotopic resonance. Interestingly, Lobysheva et al. have recently not only confirmed the effect of deuterium content in water on the function of mitochondria, but also concluded that

 

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Fig. 1: The deuterium kinetic isotope effect and its consequences.

figure 1

a, Comparison between protium (H) and deuterium (D), showing the difference in atomic mass between the two species. b, The different extent of activation energy for C–H and C–D cleavage steps. c, A representation of the deuterium kinetic isotope effect (DKIE) for cytochrome P450 (CYP)-mediated oxidative metabolism. d, Ranking of the main CYP-mediated oxidative transformations in terms of sensitivity to deuteration and approximate DKIE values.

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826779/

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Human studies involving deuterated water can be found in the areas of whole body metabolism, cell proliferation and DNA synthesis (6062). In a typical study the subject drinks 50 mL of D2O for several days to weeks, in which the body 2H enrichment can reach 0.5 – 1.5 %. These doses and enrichments, as well as experiences with heavy water in humans in general, have been deemed safe with no adverse effects. The only known acute side effect is transient vertigo or nausea which may occur following the initial D2O intake. These symptoms are apparently due to the hair cells of the inner ear vestibular apparatus detecting differences in bulk flow properties of water during the transient period of changing 2H enrichment. Administering the D2O slowly or using lower enriched D2O can further reduce these symptoms (60). In a typical DMI study involving human subjects, [6,6’−2H2]-glucose is administered at a dose of 0.75 g per kg body weight. A dose of 60 g corresponds to 330 mmol glucose or 660 mmol 2H. An 80 kg human subject with a 70% water content contains 716 mmol natural abundance 2H (0.0115 %). The deuterons from [6,6’−2H2]-glucose will, via metabolic breakdown, primarily end up in the body water, so that the body water 2H content rises from 716 mmol to 1376 mmol or equivalently from 115 ppm to 221 ppm enrichment. The relatively small amount of 2H associated with DMI studies based on [6,6’−2H2]-glucose therefore raises the 2H enrichment by only a modest amount. Performing 5 DMI scans longitudinally keeps the overall body 2H enrichment well below 0.1%, even when assuming that no 2H leaves the body throughout the longitudinal study.

While all human studies that involve deuterium keep the overall body 2H enrichment well below 1%, the use of deuterated substrates such as [6,6’−2H2]-glucose can raise the blood substrate 2H enrichment during and shortly after administration to levels well in excess of 15%. Depending on the exact route of administration (intravenously or oral) and starting plasma glucose levels, the 2H enrichment of blood glucose can reach 60 – 75%. It is well known that the replacement of protons with deuterons can lead to a large kinetic isotope effect (KIE) in which reaction rates in the presence of deuterium (kD) are reduced relative to those involving only protons (kH). Even though a KIE can be expected for any isotope, the large relative mass increase during the replacement of 1H with 2H leads to the theoretically largest KIE = kH/kD of > 7, depending on the type of chemical bond and the temperature (63). While large deuterium KIEs can be observed for select chemical reactions, the majority of in vitro reactions are characterized by KIEs closer to unity (55,64). A KIE for an individual enzyme will only have a large effect on the flux through an entire metabolic pathway in vivo if that the enzyme is rate-limiting. While KIE measurements in vivo are sparse, data from Funk et al. (65) on KIEs of [U-2H7]-glucose in rat heart and our own data on KIEs of [6,6’−2H2]-glucose in rat brain and tumor cells (66) all indicate a very small KIE for glycolytic glucose metabolism. While the KIEs for deuterated glucose in vivo appear small, they need to be established for every unique substrate and possibly even for each position within a substrate. Despite the presence of a small KIE, the safety of deuterated glucose for human use is well established by extensive studies of human body metabolism (67), as well as studies in infants (68).

 

 

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