Favorable Effects of a Ketogenic Diet on Physical Function, Perceived Energy, and Food Cravings in Women with Ovarian or Endometrial Cancer: A Randomized, Controlled Trial

Caroline W Cohen, Kevin R Fontaine, Rebecca C Arend, Taraneh Soleymani, Barbara A Gower, Caroline W Cohen, Kevin R Fontaine, Rebecca C Arend, Taraneh Soleymani, Barbara A Gower

Abstract

Ketogenic diets (KDs) are gaining attention as a potential adjuvant therapy for cancer, but data are limited for KDs' effects on quality of life. We hypothesized that the KD would (1) improve mental and physical function, including energy levels, (2) reduce hunger, and (3) diminish sweet and starchy food cravings in women with ovarian or endometrial cancer. Participants were randomized to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS: high-fiber, lower-fat). Questionnaires were administered at baseline and after 12 weeks on the assigned diet to assess changes in mental and physical health, perceived energy, appetite, and food cravings. We assessed both between-group differences and within-group changes using ANCOVA and paired t-tests, respectively. After 12 weeks, there was a significant between-group difference in adjusted physical function scores (p < 0.05), and KD participants not receiving chemotherapy reported a significant within-group reduction in fatigue (p < 0.05). There were no significant between-group differences in mental function, hunger, or appetite. There was a significant between-group difference in adjusted cravings for starchy foods and fast food fats at 12 weeks (p < 0.05 for both), with the KD group demonstrating less frequent cravings than the ACS. In conclusion, in women with ovarian or endometrial cancer, a KD does not negatively affect quality of life and in fact may improve physical function, increase energy, and diminish specific food cravings. This trial was registered at ClinicalTrials.gov as NCT03171506.

Keywords: endometrial cancer; fatigue; food cravings; ketogenic diet; mental function; ovarian cancer; physical function; quality of life.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Physical component summary scores at 12 weeks by diet group and (B) mental component summary at 12 weeks. Values are adjusted means ± SEM. * Denotes a significant between-group difference (p < 0.05) from ACS arm by ANCOVA, using baseline values and chemotherapy status as covariates. ACS, n = 20; KD, n = 23.

References

    1. Zhou W., Mukherjee P., Kiebish M.A., Markis W.T., Mantis J.G., Seyfried T.N. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr. Metab. 2007;4:5. doi: 10.1186/1743-7075-4-5.
    1. Zuccoli G., Marcello N., Pisanello A., Servadei F., Vaccaro S., Mukherjee P., Seyfried T.N. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report. Nutr. Metab. 2010;7:33. doi: 10.1186/1743-7075-7-33.
    1. Sremanakova J., Sowerbutts A.M., Burden S. A systematic review of the use of ketogenic diets in adult patients with cancer. J. Hum. Nutr. Diet. 2018 doi: 10.1111/jhn.12587.
    1. Lawrence D.P., Kupelnick B., Miller K., Devine D., Lau J. Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J. Natl. Cancer Inst. Monogr. 2004;32:40–50. doi: 10.1093/jncimonographs/lgh027.
    1. Servaes P., Verhagen C., Bleijenberg G. Fatigue in cancer patients during and after treatment: Prevalence, correlates and interventions. Eur. J. Cancer. 2002;38:27–43. doi: 10.1016/S0959-8049(01)00332-X.
    1. Cella D., Davis K., Breitbart W., Curt G., Fatigue C. Cancer-related fatigue: Prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J. Clin. Oncol. 2001;19:3385–3391. doi: 10.1200/JCO.2001.19.14.3385.
    1. Wang X.S., Zhao F., Fisch M.J., O’Mara A.M., Cella D., Mendoza T.R., Cleeland C.S. Prevalence and characteristics of moderate to severe fatigue: A multicenter study in cancer patients and survivors. Cancer. 2014;120:425–432. doi: 10.1002/cncr.28434.
    1. Williams L.A., Agarwal S., Bodurka D.C., Saleeba A.K., Sun C.C., Cleeland C.S. Capturing the patient’s experience: Using qualitative methods to develop a measure of patient-reported symptom burden: An example from ovarian cancer. J. Pain Symptom Manag. 2013;46:837–845. doi: 10.1016/j.jpainsymman.2013.02.007.
    1. Bower J.E. Cancer-related fatigue—Mechanisms, risk factors, and treatments. Nat. Rev. Clin. Oncol. 2014;11:597–609. doi: 10.1038/nrclinonc.2014.127.
    1. Ebede C.C., Jang Y., Escalante C.P. Cancer-related fatigue in cancer survivorship. Med. Clin. N. Am. 2017;101:1085–1097. doi: 10.1016/j.mcna.2017.06.007.
    1. Tan-Shalaby J.L., Carrick J., Edinger K., Genovese D., Liman A.D., Passero A.V., Shah R.B. Modified Atkins diet in advanced malignancies-final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System. Nutr. Metab. 2016;13:52. doi: 10.1186/s12986-016-0113-y.
    1. Toth C., Clemens Z. Halted progression of soft palate cancer in a patient treated with the Paleolithic ketogenic diet alone: A 20-months follow-up. Am. J. Med. Case Rep. 2016;4:288–292.
    1. Klement R.J. Beneficial effects of ketogenic diets for cancer patients: A realist review with focus on evidence and confirmation. Med. Oncol. 2017;34:132. doi: 10.1007/s12032-017-0991-5.
    1. Breymeyer K.L., Lampe J.W., McGregor B.A., Neuhouser M.L. Subjective mood and energy levels of healthy weight and overweight/obese healthy adults on high-and low-glycemic load experimental diets. Appetite. 2016;107:253–259. doi: 10.1016/j.appet.2016.08.008.
    1. McClernon F.J., Yancy Jr.W.S., Eberstein J.A., Atkins R.C., Westman E.C. The effects of a low-carbohydrate ketogenic diet and a low-fat diet on mood, hunger, and other self-reported symptoms. Obesity. 2007;15:182–187. doi: 10.1038/oby.2007.516.
    1. Gibson A.A., Seimon R.V., Lee C.M., Ayre J., Franklin J., Markovic T.P., Caterson I.D., Sainsbury A. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes. Rev. 2015;16:64–76.
    1. Martin C.K., Rosenbaum D., Han H., Geiselman P.J., Wyatt H.R., Hill J.O., Brill C., Bailer B., Miller B.V., III., Stein R., et al. Change in food cravings, food preferences, and appetite during a low-carbohydrate and low-fat diet. Obesity. 2011;19:1963–1970. doi: 10.1038/oby.2011.62.
    1. Cohen C.W., Fontaine K.R., Arend R.C., Alvarez R.D., Leath C.A., III, Huh W.K., Bevis K.S., Kim K.H., Straughn J.M., Jr., Gower B.A. A ketogenic diet reduces central obesity and serum insulin in women with ovarian or endometrial cancer. J. Nutr. 2018;148:1253–1260. doi: 10.1093/jn/nxy119.
    1. Ware J., Jr., Kosinski M., Keller S.D. A 12-Item Short-Form Health Survey: Construction of scales and preliminary tests of reliability and validity. Med. Care. 1996;34:220–233. doi: 10.1097/00005650-199603000-00003.
    1. Ware J.E., Kosinski M., Keller S.D. How to Score the SF-12 Physical and Mental Health Survey Summary Scales. 2nd ed. The Health Institute, New England Medical Center Press; Boston, MA, USA: 1995.
    1. Gandek B., Ware J.E., Aaronson N.K., Apolone G., Bjorner J.B., Brazier J.E., Bullinger M., Kaasa S., Leplege A., Prieto L., et al. Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: Results from the IQOLA Project. J. Clin. Epidemiol. 1998;51:1171–1178. doi: 10.1016/S0895-4356(98)00109-7.
    1. Bhandari N.R., Kathe N., Hayes C., Payakachat N. Reliability and validity of SF-12v2 among adults with self-reported cancer. Res. Soc. Adm. Pharm. 2018 doi: 10.1016/j.sapharm.2018.01.007.
    1. Flint A., Raben A., Blundell J.E., Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int. J. Obes. Relat. Metab. Disord. 2000;24:38–48. doi: 10.1038/sj.ijo.0801083.
    1. Stock S., Leichner P., Wong A.C., Ghatei M.A., Kieffer T.J., Bloom S.R., Chanoine J.P. Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger responses to a mixed meal in anorexic, obese, and control female adolescents. J. Clin. Endocrinol. Metab. 2005;90:2161–2168. doi: 10.1210/jc.2004-1251.
    1. White M.A., Whisenhunt B.L., Williamson D.A., Greenway F.L., Netemeyer R.G. Development and validation of the food-craving inventory. Obes. Res. 2002;10:107–114. doi: 10.1038/oby.2002.17.
    1. Rock C.L., Doyle C., Demark-Wahnefried W., Meyerhardt J., Courneya K.S., Schwartz A.L., Bandera E.V., Hamilton K.K., Grant B., McCullough M., et al. Nutrition and physical activity guidelines for cancer survivors. Cancer J. Clin. 2012;62:275–276. doi: 10.3322/caac.21142.
    1. Hamilton K.K. In: Nutritional Needs of the Adult Oncology Patient, in Oncology Nutrition for Clinical Practice. Leser M., Ledesma N., editors. Academy of Nutrition and Dietetics; Chicago, IL, USA: 2013. pp. 33–39.
    1. Brown J.C., Harhay M.O., Harhay M.N. Patient-reported versus objectively-measured physical function and mortality risk among cancer survivors. J. Geriatr. Oncol. 2016;7:108–115. doi: 10.1016/j.jgo.2016.01.009.
    1. Brown J.C., Harhay M.O., Harhay M.N. Physical function as a prognostic biomarker among cancer survivors. Br. J. Cancer. 2015;112:112–194. doi: 10.1038/bjc.2014.568.
    1. Cheung A.S., Rooy C.D., Hoermann R., Joon D.L., Zajac J.D., Grossmann M. Quality of life decrements in men with prostate cancer undergoing androgen deprivation therapy. Clin. Endocrinol. 2017;86:388–394. doi: 10.1111/cen.13249.
    1. Patel A.R., Lester R.T., Marra C.A., van der Kop M.L., Ritvo P., Engel L., Karanja S., Lynd L.D. The validity of the SF-12 and SF-6D instruments in people living with HIV/AIDS in Kenya. Health Qual. Life Outcomes. 2017;15:143. doi: 10.1186/s12955-017-0708-7.
    1. Bennett S.J., Oldridge N.B., Eckert G.J., Embree J.L., Browning S., Hou N., Chui M., Deer M. Murray MD Comparison of quality of life measures in heart failure. Nurs. Res. 2003;52:207–216. doi: 10.1097/00006199-200307000-00001.
    1. Kunitake H., Russell M.M., Zheng P., Yothers G., Land S.R., Petersen L., Fehrenbacher L., Giguere J.K., Wickerham D.L., Ko C.Y., et al. Quality of life and symptoms in long-term survivors of colorectal cancer: Results from NSABP protocol LTS-01. J. Cancer Surv. 2017;11:111–118. doi: 10.1007/s11764-016-0567-y.
    1. Schulman-Green D., Ercolano E., Dowd M., Schwartz P., McCorkle R. Quality of life among women after surgery for ovarian cancer. Palliat. Support Care. 2008;6:239–247. doi: 10.1017/S1478951508000497.
    1. Harvey C., Schofield G., Williden M., The lived experience of healthy adults following a ketogenic diet: A qualitative study [(accessed on 10 May 2018)];J. Holist. Perform. 2018 Available online: .
    1. Sarafidis P.A., Bakris G.L. The antinatriuretic effect of insulin: An unappreciated mechanism for hypertension associated with insulin resistance? Am. J. Nephrol. 2007;27:44–54. doi: 10.1159/000098955.
    1. Rabast U., Vornberger K.H., Ehl M. Loss of weight, sodium and water in obese persons consuming a high- or low-carbohydrate diet. Ann. Nutr. Metab. 1981;25:341–349. doi: 10.1159/000176515.
    1. Kolanowski J. On the mechanisms of fasting natriuresis and of carbohydrate-induced sodium retention. Diabete Metab. 1977;3:131–143.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa