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Monday, February 15, 2021

Weird biochemistry on the Internet

Is deuterium toxic? Does glyphosate destroy resistance to Covid? Does it cause Alzheimer's disease?

I Is deuterium really toxic? Does glyphosate really destroy resistance to Covid? Does it cause Alzheimer's disease? Does butter really treat cancer because it is low in deuterium? And what in the world is this structured water everyone's talking about, and where can I buy it? These are some of the questions a reader might ask after perusing an alternative medicine website. I searched through the scientific peer-reviewed literature to see if any of these claims have any merit.

What is deuterium?

Deuterium is a naturally occurring non-radioactive isotope of hydrogen. It is 0.015625% as abundant as normal hydrogen, or 156 parts per million. The concentration of pure normal water is 1000 grams per liter, which chemists express as 55.6 moles per liter (M), so the concentration of monodeuterated water or HDO, which has one deuterium and one hydrogen, is 8.6 mM, about twice as high as Ca2+. The concentration of D2O, which has two deuterium atoms, is about 1.357 μM, which is so low as to be insignificant.

Deuterium bound to an oxygen in water is fleeting: it exchanges with hydrogen from water so rapidly that we can never say what any particular water molecule is composed of. Even when it's attached to a carbon in a protein molecule, deuterium will exchange with hydrogens in the course of a few minutes.

It is well accepted that, because of its higher mass, deuterium could cause a slowing effect on enzymes that rely on hydrogen ions. This does not mean that deuterium is toxic, or that getting rid of it will benefit you in any way. Claims that deuterium is produced during inflammation, that lipoxygenase produces deuterium-depleted water, that it “wrecks” the mitochondrial ATPase pump, and that butter is low in deuterium and therefore good for you, are not supported by any evidence in the literature.

Is deuterium toxic?

Most of the articles on deuterium discuss deuterium isotope dilution or stable isotope labeling. One study gave 400 ml of 70 atom% deuterium to participants to study protein synthesis. If it were even slightly toxic, they'd never be permitted to do this. But there are some that studied whether it is toxic.

A group from Islamic Azad Univ in Iran [1] in the Turkish Journal of Pharmacological Science claimed that water with deuterium depleted to 15 and 30 ppm, known as deuterium-depleted water or DDW, reduced inflammation in rats. The inflammation was induced by cecal ligation and puncture, which induces lethal sepsis. The authors claimed that DDW reduced COX-2, an enzyme that is a gateway to prostaglandins, at a significance level of p<0.05.

Another study in Ukraine found that feeding rats 10 ppm DDW increased weight gain, apparently because the rats drank 1 1/2 times as much of it as their regular MilliQ purified water.[2] DDW increased superoxide dismutase activity from 15.6±3.2 to 27±2.4 units. This means DDW would reduce the concentration of harmful reactive oxygen species like superoxide. If this were true, then the reverse experiment, i.e. feeding them pure D2O, would have produced a hugely toxic effect, but few papers have ever reported this. In one that did,[3] also from Iran, the authors put up to 300000 ppm D2O on their cultured cells and found no effect unless celecoxib or indomethacin was also added, in which case the highest dose of D2O, in which 30% of the water was replaced by heavy water, produced a 25% reduction in cell growth.

Other papers claim that DDW does not inhibit the production of reactive oxygen species, but instead enhances it, suggesting that it could enhance inflammation and thus might be useful for treating cancer. One points out, correctly, that no widely accepted mechanism of DDW on anticancer action has emerged.[4] They propose that DDW between 50 and 105 ppm increases the mitochondrial membrane potential, causing inflammation, slower growth, and apoptosis, which is desirable for killing cancer cells, but lower concentrations cause a restoration of redox equilibrium and resumed growth.

Here's a tip: whenever the effect goes one way or the other depending on the exact concentration, or when an enormous concentration is needed to see an effect, it is usually a sign of bad science.

Conclusion: there is no support in the scientific literature for deuterium being toxic even at very high doses.

Deuterium and lipoxygenase

Lipoxygenase is an enzyme that converts arachidonic acid to bioactive lipids and prostaglandins. One group in Moscow [5] found that deuteration of arachidonic acid at C7, C10, and C13, known as the bis-allylic positions, dramatically reduced the kinetic rate of COX-2 and 15-lipoxygenase-2. No D2O was used here; the authors replaced carbon-hydrogen bonds with carbon-deuterium bonds.

The biggest effect was with 13,13-d2-arachidonic acid, where the Vmax (the maximum rate of the enzyme reaction) of 15-lox-2 was reduced by 188-fold. They suggest that these deuterated lipids could be given to patients as anti-inflammatory agents.

Extrapolating to the normal abundance of D, we would expect the amount of deuterium in the body to have a 6400-fold smaller effect, which would be unmeasurably small, but there is no doubt that deuterium can affect enzyme rates.

Conclusion: there is no support in the scientific literature for a physiologically relevant effect on enzyme reactions at ordinary levels.

Structured water

Structured water is water that is stuck in the restricted space of biological macromolecules, at the membrane interface, or surrounding a nanoparticle. Here is the claim on one vitamin web page:

“Problems arise when you cannot make enough structured water to sequester all the deuterium. The deuterium gets loose, causing mitochondrial dysfunction, impairing energy production and contributing to chronic disease.”

I could find nothing to support this claim. A paper in Nat Struct Mol Biol [6] [paywalled] says that ordered water molecules are important for proton translocation. There are thousands of papers on deuterium, mostly using deuterium labeling or hydrogen-deuterium exchange mass spectrometry (a powerful technique for studying proteins that I've used many times), but a few do talk about ATP. One paper that does, from researchers in Suwon, Korea [7], says that D2O stimulated the p53-cyclin-dependent kinase (CDK) pathway, leading to an increase in the ATP/ADP ratio. D2O also inhibited proliferation of cultured hepatic stellate cells that have been transactivated to a myofibroblastic phenotype. Activation means that cell proliferation is inhibited, as happens in liver fibrosis, so it's an important thing to study.

The authors find that D2O's effect might be mediated by a decrease in aquaporin-11, a protein that facilitates transport of water out of the cell. They found that at 30% D2O, cell proliferation was reduced by about 20 percent. At 50% D2O, it was reduced by about 50%. This appears to be a real effect, and it's interesting for what it tells us about aquaporin, but again at the normal levels of 0.016 percent we would expect no measurable effect. Adding any exogenous chemical, even D2O, at 55.6 molar concentration (which for D2O is 1110 grams per liter), is almost certain to do something.


The tox literature is full of speculative hypotheses about various chemicals that may or may not be toxic at concentrations attained in the body. There are also many papers of marginal scientific value. So I am skeptical about any claims of toxicity for glyphosate. I could also find no articles that mentioned glyphosate and COVID-19 in the same paper.

One interesting claim is that glyphosate acts as an amino acid analogue of glycine and is incorporated into proteins. The author claims that this may be why glyphosate is

“. . . a plausible contributory cause of diabetes, obesity and Alzheimer's disease, amyotrophic lateral sclerosis (ALS), autism, multiple sclerosis and prion diseases, anencephaly, chronic kidney disease of unknown etiology (CKDu), and gout.”[8]

The problem these authors face is that researchers on environmental toxins have a history of making hysterical claims based on a limited understanding of pharmacological toxicology. Femtomolar concentrations of molecules are easily detected nowadays. If an article doesn't mention the actual amounts that were detected and just says something was “found,” the claim has little scientific value.

The article claiming glyphosate is incorporated into proteins [9] is actually a highly speculative review that essentially says if it were incorporated into proteins it might be harmful. The main connection the article makes to Alzheimer's is GSK-3, by which the authors presumably mean GSK-3β, which is an enzyme that phosphorylates tau (which is associated with neuronal death). GSK-3, they say, contains a highly conserved glycine-rich N-terminus. And β-amyloid contains two glycines. Or maybe, they speculate, glyphosate chelates magnesium and induces a deficiency.

Luckily for the authors, I was not a peer reviewer: I would have ripped those unsubstantiated claims to shreds. But the connection to glycine is interesting. The primary metabolite of glyphosate is amino­methyl­phosphonic acid, but glyphosate can be metabolized to glycine in some bacteria,[10] so it's possible that some atoms in glyphosate could end up as glycine in proteins.


Just because the claims discussed here are not supported by research or are based on a misunder­standing of basic molecular biology does not necessarily mean they are false. They may even be valuable. Unconventional theories, even if they're invented from thin air, can generate interest in science. They may encourage readers, originally attracted by their conspiracy value, who would never dream of opening a copy of Alberts and never heard of Lehninger, to seek out confirmatory information. Censoring them would deprive people of the chance to learn how to distinguish valid from invalid information. This is something that even science struggles with.

The ultimate fallacy would be to use science, the United Nations, a religious text, or any other source as an authority for what is true. If Big Tech claims that truth can be defined by authority, they will undermine what remains of their credibility.

[1] Fatemi F, Golbodagh A, Hojihosseini R, Dadkhah A, Akbarzadeh K, Dini S, Malayeri MRM. Anti-inflammatory Effects of Deuterium-Depleted Water Plus Rosa Damascena Mill. Essential Oil Via Cyclooxygenase-2 Pathway in Rats. Turk J Pharm Sci. 2020 Feb;17(1):99–107. doi: 10.4274/tjps.galenos.2018.24381. PMID: 32454767; PMCID: PMC7227869.

[2] Halenova T, Zlatskiy I, Syroeshkin A, Maximova T, Pleteneva T. Deuterium-Depleted Water as Adjuvant Therapeutic Agent for Treatment of Diet-Induced Obesity in Rats. Molecules. 2019 Dec 19;25(1):23. doi: 10.3390/molecules25010023. PMID: 31861678; PMCID: PMC6982901.

[3] Hassanzade A, Mandegary A, Sharif E, Rasooli R, Mohammadnejad R, Masoumi-Ardekani Y. Cyclooxygenase inhibitors combined with deuterium-enriched water augment cytotoxicity in A549 lung cancer cell line via activation of apoptosis and MAPK pathways. Iran J Basic Med Sci. 2018 May;21(5):508–516. doi: 10.22038/IJBMS.2018.25366.6269. PMID: 29922432; PMCID: PMC6000214.

[4] Zhang X, Gaetani M, Chernobrovkin A, Zubarev RA. Anticancer Effect of Deuterium Depleted Water - Redox Disbalance Leads to Oxidative Stress. Mol Cell Proteomics. 2019 Dec;18(12):2373–2387. doi: 10.1074/mcp.RA119.001455. PMID: 31519768; PMCID: PMC6885702.

[5] Chistyakov DV, Filimonov IS, Azbukina NV, Goriainov SV, Chistyakov VV, Fomich MA, Bekish AV, Shmanai VV, Sergeeva MG, Shchepinov MS. Deuterated Arachidonic Acids Library for Regulation of Inflammation and Controlled Synthesis of Eicosanoids: An In Vitro Study. Molecules. 2018 Dec 15;23(12):3331. doi: 10.3390/molecules23123331. PMID: 30558277; PMCID: PMC6321560.

[6] Grba DN, Hirst J. Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation. Nat Struct Mol Biol. 2020 Oct;27(10):892–900. doi: 10.1038/s41594-020-0473-x. PMID: 32747785.

[7] Lee PJ, Park HJ, Cho N, Kim HP. Aquaporin 11-Dependent Inhibition of Proliferation by Deuterium Oxide in Activated Hepatic Stellate Cells. Molecules. 2018 Dec 5;23(12):3209. doi: 10.3390/molecules23123209. PMID: 30563120; PMCID: PMC6321126.

[8] Gunatilake S, Seneff S, Orlando L. Glyphosate's Synergistic Toxicity in Combination with Other Factors as a Cause of Chronic Kidney Disease of Unknown Origin. Int J Environ Res Public Health. 2019 Jul 31;16(15):2734. doi: 10.3390/ijerph16152734. PMID: 31370256; PMCID: PMC6695815.

[9] Samsel A., Seneff S. Glyphosate, pathways to modern diseases V: Amino acid analogue of glycine in diverse proteins. J. Biol. Phys. Chem. 2016;16:9–46. doi: 10.4024/03SA16A.jbpc.16.01. http://amsi.ge/jbpc/11616/jbpc11616.html

[10] Pipke R, Amrhein N, Jacob GS, Schaefer J, Kishore GM. Metabolism of glyphosate in an Arthrobacter sp. GLP-1. Eur J Biochem. 1987 Jun 1;165(2):267–273. doi: 10.1111/j.1432-1033.1987.tb11437.x. PMID: 2439330.

feb 15 2021, 3:54 am

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