Heavy isotope diet

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Chemical structures of ethyl linoleate — natural (top) and its deuterated version 11,11-D2-ethyl linoleate. Protium hydrogen atoms (H) are explicitly shown where they are replaced with deuterium atoms (D).

Heavy isotope diet is the consumption of nutrients in which some atoms are replaced with their heavier non-radioactive isotopes, such as deuterium(2H) or heavy carbon (13C). Biomolecules that incorporate heavier isotopes give rise to more stable molecular structures under certain circumstances, which is hypothesized to increase resistance to damage associated with ageing[1] or diseases.[2][3]

Medicines with some hydrogen atoms substituted with deuterium are called deuterated drugs, while substances that are essential nutrients can be used as food constituents, making this food "isotopic". Consumed with food, these nutrients become building material for the body. The examples are deuterated polyunsaturated fatty acids, essential aminoacids,[4] DNA bases such as cytosine,[5] or heavy water and glucose.[6]

Suggested mechanism

One of the most pernicious and irreparable types of oxidative damage inflicted by reactive oxygen species (ROS) upon biomolecules involves the carbon-hydrogen bond cleavage (hydrogen abstraction). Intriguingly, the biomolecules most damageable by this type of damage belong to the group of essential nutrients (10 out of 20 amino acids; nucleosides at certain conditions (conditionally essential); all polyunsaturated fatty acids). In theory, replacing hydrogen with deuterium "reinforces" the bond due to the kinetic isotope effect, and such reinforced biomolecules taken up by the body will be more resistant to ROS.[7]

Deuterated omega-6 fatty acids for humans with degenerative diseases

The company Retrotope pioneered the development a source of deuterated omega-6 fatty acid di-deuterated linoleic acid ethyl ester (RT001) as a food additive for potential treatment of neurodegenerative diseases such as Friedreich’s ataxia and infantile neuroaxonal dystrophy. FDA has granted it an orphan drug designation and it passed the Phase I/II clinical trials (as of 2018).[8]

See also

References

  1. ^ "Heavy hydrogen keeps yeast looking good".
  2. ^ Tsikas, Dimitrios (2017). "Combating atherosclerosis with heavy PUFAs: Deuteron not proton is the first". Atherosclerosis. 264: 79–82. doi:10.1016/j.atherosclerosis.2017.07.018. PMID 28756876.
  3. ^ "Deuterium diet". Chemistry & Industry. 84 (9): 30–33. 2020. doi:10.1002/cind.849_7.x. S2CID 240909784.
  4. ^ Korneenko, Tatyana V; Pestov, Nikolay B; Hurski, Alaksiej L; Fedarkevich, Artsiom M; Shmanai, Vadim V; Brenna, J. Thomas; Shchepinov, Mikhail S (2017). "A strong developmental isotope effect in Caenorhabditis elegans induced by 5,5-deuterated lysine". Amino Acids. 49 (5): 887–894. doi:10.1007/s00726-017-2386-5. PMID 28161800. S2CID 625937.
  5. ^ Woodcock, Clayton B; Ulashchik, Egor A; Poopeiko, Nikolai E; Shmanai, Vadim V; Reich, Norbert O; Shchepinov, Mikhail S (2016). "Rational Manipulation of DNA Methylation by Using Isotopically Reinforced Cytosine". ChemBioChem. 17 (21): 2018–2021. doi:10.1002/cbic.201600393. PMID 27595234. S2CID 19507501.
  6. ^ Li, Xiyan; Snyder, Michael P (2016). "Yeast longevity promoted by reversing aging-associated decline in heavy isotope content". npj Aging and Mechanisms of Disease. 2: 16004. doi:10.1038/npjamd.2016.4. PMC 5515009. PMID 28721263.
  7. ^ Shchepinov, Mikhail S (2007). "Reactive Oxygen Species, Isotope Effect, Essential Nutrients, and Enhanced Longevity". Rejuvenation Research. 10 (1): 47–59. doi:10.1089/rej.2006.0506. PMID 17378752.
  8. ^ Schmidt, Charles (2017). "First deuterated drug approved". Nature Biotechnology. 35 (6): 493–494. doi:10.1038/nbt0617-493. PMID 28591114. S2CID 205269152.

External links