Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Deuterium Content of the Organic Compounds in Food Has an Impact on Tumor Growth in Mice

Version 1 : Received: 12 June 2022 / Approved: 13 June 2022 / Online: 13 June 2022 (09:49:32 CEST)

How to cite: Somlyai, G.; Nagy, L.I.; Puskás, L.G.; Papp, A.; Kovács, B.Z.; Fórizs, I.; Czuppon, G.; Somlyai, I. Deuterium Content of the Organic Compounds in Food Has an Impact on Tumor Growth in Mice. Preprints 2022, 2022060177. https://doi.org/10.20944/preprints202206.0177.v1 Somlyai, G.; Nagy, L.I.; Puskás, L.G.; Papp, A.; Kovács, B.Z.; Fórizs, I.; Czuppon, G.; Somlyai, I. Deuterium Content of the Organic Compounds in Food Has an Impact on Tumor Growth in Mice. Preprints 2022, 2022060177. https://doi.org/10.20944/preprints202206.0177.v1

Abstract

Research with deuterium-depleted water (DDW) in the last two decades proved that deuterium/hydrogen ratio has a key role in cell cycle regulation and cellular metabolism. The present study aimed to investigate the possible effect of deuterium-depleted organic compounds (DDOC) alone and in combination with DDW on cancer growth in two in vivo mouse models. To produce DDOC, drinking water of laying hens was replaced with DDW (25 ppm) for 6 weeks, resulting in 60 ppm D level in dried egg yolk that was used as deuterium-depleted food additive. In one model, 4T1, a cell line with high metastatic capacity to the lung, was inoculated in the mice’s mammary pad. After three weeks of treatment with DDW and/or DDOC, the tumor volume in the lungs was smaller in all treated groups vs. controls with natural D level. Tumor growth and survival in mice transplanted with MCF-7 breast cancer cell line showed that the anticancer effect of DDW was enhanced by food containing the deuterium-depleted yolk. The study confirmed the importance of D/H ratio not only in consumed water but also in metabolic water produced by the mitochondria while oxidizing nutrient molecules. This is in line with the concept that initiation of cell growth requires the cells to generate a higher D/H ratio, but DDW, DDOC, or the naturally low-D lipids in a ketogenic diet, have significant effect on tumor growth by preventing the cells from raising D/H ratio to the threshold.

Keywords

Deuterium-depleted water (DDW); deuterium-depleted organic compounds (DDOC); anticancer drug development; D/H ratio; production of metabolic water; ketogenic diet

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Comments (3)

Comment 1
Received: 4 July 2022
Commenter: (Click to see Publons profile: )
The commenter has declared there is no conflict of interests.
Comment: The preprint paper of Somlyai et al. (1) provides long-awaited experimental animal data to show the efficacy of deuterium depleted nutrient substrates in the treatment of cancer, in addition to such known effects regarding deuterium depleted drinking water in similar models. The latter is well described and cited in the manuscript.

The former, i.e. nutrients being directly involved in intracellular deuterium depleted metabolic water production by mitochondrial (complete) substrate oxidation are explained elsewhere by the same authors. These papers are worth reviewing for clarity and mechanism of action by the many deuterium depleting water and proton exchange reactions in the tricarboxylic acid cycle (2, 3). Of course, these effects all depend on the deuterium content of nutrients, as the source of metabolic water (4), which has specifically been addressed as “We herein recommend that ketogenic dieting experimental protocols use fat sources with known deuterium content and ratios (5), and only when natural deuterium depleting potential of fatty acids upon oxidation of the β carbon is established should the study be introduced into the literature as such.”

This work moves such previous arguments further towards translational medicine and the clinics.

References:
1. Somlyai, G.; Nagy, L.I.; Puskás, L.G.; Papp, A.; Kovács, B.Z.; Fórizs, I.; Czuppon, G.; Somlyai, I. Deuterium Content of the Organic Compounds in Food Has an Impact on Tumor Growth in Mice . Preprints, 2022, 2022060177. doi: 10.20944/preprints202206.0177.v1
2. Boros, L.G.; D’Agostino, D.P.; Katz, H.E.; Roth, J.P.; Meuillet, E.J.; Somlyai, G. Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle. Medical Hypotheses, 2016, 87: 69-74. https://doi.org/10.1016/j.mehy.2015.11.016
3. Boros, L.G.; Somlyai, G. Compartmentalized NADPH synthesis, intramolecular deuterium disequilibrium and water pools of mammalian cells. Comment on: Lewis CA, Parker SJ, Fiske BP, et al. Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol Cell. 2014;55:253–263. http://www.cell.com/molecular-cell/comments/S1097-2765(14)00402-X
4. Boros, L.G.; Collins, T.Q.; Somlyai, G. What to eat or what not to eat—that is still the question Neuro-Oncology, 2017, 19(4): 595–596. https://doi.org/10.1093/neuonc/now284
5. Duan JR Billault I Mabon F et al. . Natural deuterium distribution in fatty acids isolated from peanut seed oil: a site-specific study by quantitative 2H NMR spectroscopy. Chembiochem. 2002;3(8):752–759.
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Comment 2
Received: 20 July 2022
Commenter:
The commenter has declared there is no conflict of interests.
Comment: The authors perform a solid study on the impact of deuterium depletion on the growth of tumors, observing significant impacts.

Suggestions for improvement:

  • text More information on the biological mechanism by which DDW exerts antitumor effects.
  • text Histological stains to assess any qualitative differences between the tumor populations.

This work is solid and supports present hypotheses for anticancer impact of DD. Future work should characterize the transcriptome of deuterium depleted and deuterium enriched experimental conditions. As far as I know, no such record exists in the gene expression omnibus (GEO).

We thank the authors for their contribution, and look forward to seeing the final published work.

Matthew Halma,
PhD Student, Physics of Life Processes, VU Amsterdam
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Comment 3
Received: 1 August 2022
Commenter: James C Lech
The commenter has declared there is no conflict of interests.
Comment: Biophysics.org states “the field of science is at the forefront of solving age-old human problems as well as problems of the future by developing cutting-edge technologies working to develop methods to overcome disease, eradicate global hunger, produce renewable energy sources, and solve countless scientific mysteries”. It entails tackling a wide array of topics, for example, how nerve cells communicate, how plant cells capture light and transform it into energy, how changes in the DNA of healthy cells can trigger their transformation into cancer cells, and an inexhaustible range of other biological problems. Biophysics is a field that applies the theories/models and methods of physics to understand how and why biological systems work. It helps to understand the mechanics of how the molecules of life are made, how different parts of a cell move and function, and how complex systems in our bodies—the brain, circulation, immune system, and others— work.

Quantum biology (QB) is the field that deals with the application of quantum mechanics (QM) to biological processes. QB is generally considered a subdivision of quantum physics. Its application to medicine is termed sub-molecular medical sciences (SMMS), and its application to agriculture is termed sub-molecular agricultural sciences (SMAS), which
indirectly also impacts SMMS. SMMS is about taking a complicated QM idea and demonstrating how it manifests itself in life, in this instance, medical treatment and/or diagnostics. SMMS is a domain that may appear hard to believe but an incredible path to be built offering novel treatment options to patients with new perspectives.

As is published in the World Health Organization Nation Report 2022:
Clinical reviews and understanding the underlying mechanisms demonstrate and classify deuterium depletion through consumption of water with significantly lowered deuterium levels, and/or diet with reduced deuterium levels and/or regulating deuterium’s metabolic activity within the body. For example, there is strong supportive evidence for prostate, brain and lung cancers, an effective early-stage treatment as a single therapy and delays conventional therapy. Even when used in conjunction with conventional therapy of radiation or chemotherapy, patient lifespan is significantly increased compared to controls. Using a scientific-technical analysis, deutenomics is found to be a cost-effective, pragmatic and accessible form of treatment to clinicians and the public. Impacts on improvements to Type 2
diabetes are to be noted.

The works in this paper by Somlyai and his team, is extremely important, and instrumental to aiding the growth and development of biophysics further.
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