Top

Published in:

01-12-2020 | Breast Cancer | Research article

Impact of a ketogenic diet intervention during radiotherapy on body composition: III—final results of the KETOCOMP study for breast cancer patients

Authors: Rainer J. Klement, Colin E. Champ, Ulrike Kämmerer, Petra S. Koebrunner, Kelley Krage, Gabriele Schäfer, M. Weigel, Reinhart A. Sweeney

Published in: Breast Cancer Research | Issue 1/2020

Abstract

Background

Obesity and low muscle mass are associated with worse outcomes of breast cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in breast cancer patients undergoing radiotherapy.

Methods

Patients with non-metastasized breast cancer were allocated to either the KD (N = 32) or the SD (N = 31) during radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters and quality of life were assessed before, during, and at the end of radiotherapy.

Results

A total of 29 KD and 30 SD patients completed the study. During radiotherapy, mean and median fasting BHB concentrations in the KD group were 0.72 and 0.49 mmol/l (range 0.06–4.9) which was significantly higher than those in the SD group (p < 2.2 × 10⁻¹⁶). There was a very small and insignificant increase in body weight and fat mass in the SD group, as well as a decrease of fat free mass. In contrast, patients in the KD group lost body weight and fat free and skeletal muscle mass quickly after diet onset, which for the most part was related to water losses. The KD did not cause further substantial changes in fat free or skeletal muscle mass, but was associated with a gradual decrease of 0.4 kg body weight and fat mass per week (p < 0.0001). The KD significantly decreased free T3 levels by 0.06 pg/ml/week (p = 6.3 × 10⁻⁵). Global quality of life remained stable in the SD group but increased in the KD group from a score of 66.7 to 75.0 (p = 0.20).

Conclusions

In breast cancer patients undergoing curative radiotherapy, a KD based on natural foods is feasible. After initial water losses, the KD tends to reduce body weight and fat mass while preserving fat free and skeletal muscle mass.

Trial registration

ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.

Available only for authorised users

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492.CrossRef

Kreis K, Plöthner M, Schmidt T, Seufert R, Schreeb K, Jahndel V, et al. Healthcare costs associated with breast cancer in Germany: a claims data analysis. Eur J Health Econ. 2020. https://doi.org/10.1007/s10198-019-01148-w.

Robinson PJ, Bell RJ, Davis SR. Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer. Maturitas. 2014. https://doi.org/10.1016/j.maturitas.2014.07.004.

Azrad M, Demark-Wahnefried W. The association between adiposity and breast cancer recurrence and survival: a review of the recent literature. Curr Nutr Rep. 2014;3:9–15.CrossRef

Caan BJ, Cespedes Feliciano EM, Prado CM, Alexeeff S, Kroenke CH, Bradshaw P, et al. Association of muscle and adiposity measured by computed tomography with survival in patients with nonmetastatic breast cancer. JAMA Oncol. 2018;94612:1–7. https://doi.org/10.1001/jamaoncol.2018.0137.CrossRef

Cespedes Feliciano E, Chen WY. Clinical implications of low skeletal muscle mass in early-stage breast and colorectal cancer. Proc Nutr Soc. 2018;77:382–7. https://doi.org/10.1017/S0029665118000423.CrossRefPubMed

Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002;20:42–51.CrossRef

Ferroni P, Riondino S, Laudisi A, Portarena I, Formica V, Alessandroni J, et al. Pretreatment insulin levels as a prognostic factor for breast cancer progression. Oncologist. 2016;21:1041–9.CrossRef

Erickson K, Patterson RE, Flatt SW, Natarajan L, Parker BA, Heath DD, et al. Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer. J Clin Oncol. 2011;29:54–60. https://doi.org/10.1200/JCO.2010.29.3183.CrossRefPubMed

10.

Villarreal-Garza C, Shaw-Dulin R, Lara-Medina F, Bacon L, Rivera D, Urzua L, et al. Impact of diabetes and hyperglycemia on survival in advanced breast cancer patients. Exp Diabetes Res. 2012;2012:732027. https://doi.org/10.1155/2012/732027.CrossRefPubMedPubMedCentral

11.

Minicozzi P, Berrino F, Sebastiani F, Falcini F, Vattiato R, Cioccoloni F, et al. High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease. Eur J Cancer. 2013;49:3881–8. https://doi.org/10.1016/j.ejca.2013.08.004.CrossRefPubMed

12.

Osborne CK, Monaco ME, Lippman ME, Kahn CR. Correlation among insulin binding, degradation, and biological activity in human breast cancer cells in long-term tissue culture. Cancer Res. 1978;38:94–102.PubMed

13.

Christodoulatos GS, Spyrou N, Kadillari J, Psallida S, Dalamaga M. The role of adipokines in breast cancer: current evidence and perspectives. Curr Obes Rep. 2019;8:413–33. https://doi.org/10.1007/s13679-019-00364-y.CrossRefPubMed

14.

Visagie MH, Mqoco TV, Liebenberg L, Mathews EH, Mathews GE, Joubert AM. Influence of partial and complete glutamine-and glucose deprivation of breast-and cervical tumorigenic cell lines. Cell Biosci. 2015;5:1–26. https://doi.org/10.1186/s13578-015-0030-1.CrossRef

15.

Edward P, Mathews EH, Visagie MH, Meyer AA, Joubert AM, Mathews GE. In vitro quantification: long-term effect of glucose deprivation on various cancer cell lines. Nutrition. 2020;74:110748. https://doi.org/10.1016/j.nut.2020.110748.

16.

Muck BR, Trotnow S, Egger H, Hommel G. Altered carbohydrate metabolism in breast cancer and benign breast affections. Arch Gynakol. 1976;221:83–91. https://doi.org/10.1007/BF00667684.CrossRefPubMed

17.

Champ CE, Volek JS, Siglin J, Jin L, Simone NL. Weight gain, metabolic syndrome, and breast cancer recurrence: are dietary recommendations supported by the data? Int J Breast Cancer. 2012;2012:506868. https://doi.org/10.1155/2012/506868.CrossRefPubMedPubMedCentral

18.

Genton L, Kyle UG, Balmer Majno S, Pichard C. Body composition changes in breast cancer patients during curative radiation therapy. Clin Nutr ESPEN. 2006;1:2–8. https://doi.org/10.1016/j.eclnm.2006.07.005.CrossRef

19.

Champ CE, Mishra MV, Showalter TN, Ohri N, Dicker AP, Simone NL. Dietary recommendations during and after cancer treatment: consistently inconsistent? Nutr Cancer. 2013;65:430–9. https://doi.org/10.1080/01635581.2013.757629.CrossRefPubMed

20.

Hyde PN, Lustberg MB, Miller VJ, LaFountain RA, Volek JS. Pleiotropic effects of nutritional ketosis: conceptual framework for keto-adaptation as a breast cancer therapy. Cancer Treat Res Commun. 2017;12:32–9. https://doi.org/10.1016/j.ctarc.2017.06.001.CrossRef

21.

Kämmerer U, Bartmann C, Wöckel A, Reuss-Borst M. Krebszellen lieben Zucker, Patientinnen brauchen Fett. Gynakologe 2019. doi:https://doi.org/10.1007/s00129-019-4459-x.

22.

Miller VJ, Villamena FA, Volek JS. Nutritional ketosis and mitohormesis: potential implications for mitochondrial function and human health. J Nutr Metab. 2018;2018:5157645.

23.

Klement RJ, Sweeney RA. Impact of a ketogenic diet intervention during radiotherapy on body composition: II. Protocol of a randomised phase I study (KETOCOMP). Clin Nutr ESPEN. 2016;12:e1–6. https://doi.org/10.1016/j.clnesp.2015.11.001.CrossRefPubMed

24.

Klement RJ, Schäfer G, Sweeney RA. A ketogenic diet exerts beneficial effects on body composition of cancer patients during radiotherapy: an interim analysis of the KETOCOMP study. J Tradit Complement Med. 2020;10:180–7 https://doi.org/10.1016/j.jtcme.2019.03.007.CrossRef

25.

Klement RJ, Sweeney RA. Impact of a ketogenic diet intervention during radiotherapy on body composition: I. Initial clinical experience with six prospectively studied patients. BMC Res Notes. 2016;9:143. https://doi.org/10.1016/j.clnesp.2015.11.001.CrossRefPubMedPubMedCentral

26.

Kämmerer U, Schlatterer C, Knoll G. Krebszellen lieben Zucker - Patienten brauchen Fett. 1st ed. Systemed; 2012.

27.

Jungvogel A. Food-based dietary guidelines in Germany. 1st ed. Bonn: Deutsche Gesellschaft für Ernährung e. V.; 2015.

28.

Burnham KP, Anderson DR. Multimodel inference: understanding AIC and BIC in model selection. Sociol Methods Res. 2004;33:261–304. https://doi.org/10.1177/0049124104268644.CrossRef

29.

Anderson DR. Model based inferences in the life sciences. New York: Springer Science+Business Media, LLC; 2008.CrossRef

30.

Nakagawa S, Johnson PCD, Schielzeth H. The coefficient of determination R2 and intra-class correlation coefficient from generalized linear mixed-effects models revisited and expanded. J R Soc Interface. 2017;14:20170213. https://doi.org/10.1098/rsif.2017.0213.CrossRefPubMedPubMedCentral

31.

Bosy-Westphal A, Schautz B, Later W, Kehaylas J, Gallagher D, Müller M. What makes a BIA equation unique? Validity of eight-electrode multifrequency BIA to estimate body composition in a healthy adult population. Eur J Clin Nutr. 2013;67:S14–21.CrossRef

32.

Bosy-Westphal A, Jensen B, Braun W, Pourhassan M, Gallagher D, Müller MJ. Quantification of whole-body and segmental skeletal muscle mass using phase-sensitive 8-electrode medical bioelectrical impedance devices. Eur J Clin Nutr. 2017;71:1061–7. https://doi.org/10.1038/ejcn.2017.27.CrossRefPubMedPubMedCentral

33.

Yuan Y, Johnson VE. Bayesian hypothesis tests using nonparametric statistics. Stat Sin. 2008;18:1185–200.

34.

Held L. An objective Bayes perspective on p-values. Biom J. 2017;59:886–8. https://doi.org/10.1002/bimj.201700068.CrossRefPubMed

35.

Benjamin DJ, Berger JO, Johannesson M, Nosek BA, Wagenmakers EJ, Berk R, et al. Redefine statistical significance. Nat Hum Behav. 2018;2:6–10. https://doi.org/10.1038/s41562-017-0189-z.CrossRefPubMed

36.

Cohen CW, Fontaine KR, Arend RC, Alvarez RD, Leath CA III, Huh WK, et al. A ketogenic diet reduces central obesity and serum insulin in women with ovarian or endometrial cancer. J Nutr. 2018;148:1253–60. https://doi.org/10.1093/jn/nxy119.CrossRefPubMed

37.

O’Hearn LA. Ketogenic diets, caloric restriction, and hormones. J Evol Heal. 2018;2:13. https://doi.org/10.15310/2334-3591.1093.CrossRef

38.

Wright C, Simone NL. Obesity and tumor growth: inflammation, immunity, and the role of a ketogenic diet. Curr Opin Clin Nutr Metab Care. 2016;19:294–9. https://doi.org/10.1097/MCO.0000000000000286.CrossRefPubMed

39.

Klement RJ, Fink MK. Dietary and pharmacological modification of the insulin/IGF-1 system: exploiting the full repertoire against cancer. Oncogenesis. 2016;5:e193. https://doi.org/10.1038/oncsis.2016.2.CrossRefPubMedPubMedCentral

40.

Deluche E, Leobon S, Desport JC, Venat-Bouvet L, Usseglio J, Tubiana-mathieu N. Impact of body composition on outcome in patients with early breast cancer. Support Care Cancer. 2018;26:861–8. https://doi.org/10.1007/s00520-017-3902-6.CrossRefPubMed

41.

Kroenke CH, Chen WY, Rosner B, Holmes MD. Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol. 2005;23:1370–8. https://doi.org/10.1200/jco.2005.01.079.CrossRefPubMed

42.

MacKay EM, Bergman HC. The relation between glycogen and water storage in the liver. J Biol Chem. 1932;96:373–80.

43.

Olsson K-E, Saltin B. Variation in total body water with muscle glycogen changes in man. Acta Physiol Scand. 1970;80:11–8. https://doi.org/10.1111/j.1748-1716.1970.tb04764.x.CrossRefPubMed

44.

Fernández-Elías VE, Ortega JF, Nelson RK, Mora-Rodriguez R. Relationship between muscle water and glycogen recovery after prolonged exercise in the heat in humans. Eur J Appl Physiol. 2015;115:1919–26. https://doi.org/10.1007/s00421-015-3175-z.CrossRefPubMed

45.

Soleimani M. Insulin resistance and hypertension: new insights. Kidney Int. 2015;87:497–9. https://doi.org/10.1038/ki.2014.392.CrossRefPubMed

46.

Champ CE, Ohri N, Klement RJ, Cantor M, Beriwal S, Glaser SM, et al. Assessing changes in the activity levels of breast cancer patients during radiation therapy. Clin Breast Cancer. 2018;18. https://doi.org/10.1016/j.clbc.2017.08.009.

47.

Allen BG, Bhatia SK, Anderson CM, Eichenberger-Gilmore JM, Sibenaller ZA, Mapuskar KA, et al. Ketogenic diets as an adjuvant cancer therapy: history and potential mechanism. Redox Biol. 2014;2:963–70. https://doi.org/10.1016/j.redox.2014.08.002.CrossRefPubMedPubMedCentral

48.

Klement RJ, Champ CE. Calories, carbohydrates, and cancer therapy with radiation: exploiting the five R’s through dietary manipulation. Cancer Metastasis Rev. 2014;33:217–29. https://doi.org/10.1007/s10555-014-9495-3.CrossRefPubMedPubMedCentral

49.

Klement RJ. Fasting, fats, and physics: combining ketogenic and radiation therapy against cancer. Complement Med Res. 2018;25:102–13. https://doi.org/10.1159/000484045.CrossRefPubMed

50.

Klement RJ. The influence of ketogenic therapy on the 5 R’s of radiobiology. Int J Radiat Biol. 2019;95:394–407. https://doi.org/10.1080/09553002.2017.1380330.CrossRefPubMed

51.

Seyfried TN, Mukherjee P, Iyikesici MS, Slocum A, Kalamian M, Spinosa J-P, et al. Consideration of ketogenic metabolic therapy as a complementary or alternative approach for managing breast cancer. Front Nutr. 2020;7:21. https://doi.org/10.3389/fnut.2020.00021.CrossRefPubMedPubMedCentral

52.

Khodabakhshi A, Akbari ME, Mirzaei HR, Mehrad-Majd H, Kalamian M, Davoodi SH. Feasibility, safety, and beneficial effects of MCT-based ketogenic diet for breast cancer treatment: a randomized controlled trial study. Nutr Cancer 2019;72:627–34. https://doi.org/10.1080/01635581.2019.1650942.

53.

Worrall J. Evidence in medicine and evidence-based medicine. Philos Compass. 2007;2:981–1022. https://doi.org/10.1111/j.1747-9991.2007.00106.x.CrossRef

Title: Impact of a ketogenic diet intervention during radiotherapy on body composition: III—final results of the KETOCOMP study for breast cancer patients
Authors: Rainer J. Klement
Colin E. Champ
Ulrike Kämmerer
Petra S. Koebrunner
Kelley Krage
Gabriele Schäfer
M. Weigel
Reinhart A. Sweeney
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Radiotherapy
Published in: Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-020-01331-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2020

Inter-tumor genomic heterogeneity of breast cancers: comprehensive genomic profile of primary early breast cancers and relapses

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk

Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis

Association of TILs with clinical parameters, Recurrence Score® results, and prognosis in patients with early HER2-negative breast cancer (BC)—a translational analysis of the prospective WSG PlanB trial

Identification and transfer of spatial transcriptomics signatures for cancer diagnosis

Correction to: Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis

Keynote webinar | Spotlight on antibody–drug conjugates in cancer