Sweet taste of heavy water

Abstract

Hydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and can add to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and chimeric G-proteins are activated by D2O but not by H2O. Lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3, suppresses the sweetness of D2O in human sensory tests, as well as the calcium release elicited by D2O in sweet taste receptor-expressing cells. The present multifaceted experimental study, complemented by homology modelling and molecular dynamics simulations, resolves a long-standing controversy about the taste of heavy water, shows that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of the detailed mechanism of action.

Heavy Water Models for Classical Molecular Dynamics: Effective Inclusion of Nuclear Quantum Effects

“…4,5 On a safer note, we have recently confirmed old claims that heavy water has a mildly but distinctly sweet taste, showing that D 2 O (unlike H 2 O) activated the human sweet taste receptor. 6 While the exact molecular mechanism of the sweet taste of D 2 O remains elusive, our simulations confirm experimental observations that in general protein stability and rigidity change (typically slightly increase) upon moving from ordinary to heavy water. 7−9 Changes in protein behavior in ordinary vs heavy water are primarily due to differences in hydrogen bonding due to NQEs; 3 namely, a reduction in vibrational zero-point energies leads to slightly stronger water−water and water−protein hydrogen bonds in D 2 O vs H 2 O.…”

“…The above differences between ordinary and heavy water, in particular kinetic effects concerning proton/deuteron transfer, are behind the very low toxicity of D 2 O to higher organisms, which only becomes an issue if a sizable amount (tens of percent) of bodily water is replaced by its deuterated analogue. , On a safer note, we have recently confirmed old claims that heavy water has a mildly but distinctly sweet taste, showing that D 2 O (unlike H 2 O) activated the human sweet taste receptor . While the exact molecular mechanism of the sweet taste of D 2 O remains elusive, our simulations confirm experimental observations that in general protein stability and rigidity change (typically slightly increase) upon moving from ordinary to heavy water. − …”

Viewpoints on the First Transatlantic GPCR Symposium for Early-Career Investigators

“…In a fully controlled experiment, unlike the 1935 paper with an N = 2, blinded human participants reportedly ranked D 2 O as more sweet than H 2 O. 13 Dr. Niv's group tracked this perception down to the sweet taste receptor homodimer T1R2/T1R3 using clever in vivo pharmacology. This was backed up with in vitro assays in transfected cells that further demonstrated that T1R2/T1R3 is activated by D 2 O.…”

“…However, chemists, with perhaps questionable lab safety protocols, have repeatedly claimed that D 2 O tastes sweet. In a fully controlled experiment, unlike the 1935 paper with an N = 2, blinded human participants reportedly ranked D 2 O as more sweet than H 2 O . Dr. Niv’s group tracked this perception down to the sweet taste receptor homodimer T1R2/T1R3 using clever in vivo pharmacology.…”

Incorporating Nuclear Quantum Effects in Molecular Dynamics

“…There have been many theoretical developments on the incorporation of NQEs in molecular simulations. Some empirical force fields [6] have been used to include NQEs implicitly, and have been able to treat protons and deuteriums differently in water [7]. Quantum wave packet dynamics is based on the exact time evolution of a quantum system according to the time-dependent Schrödinger equation and can give theoretical predictions that accurately match to experiments [8][9][10][11][12].…”