Ketogenic Diet

Our assessments of evidence for each medical benefit fall into one of these categories:

• Strong evidence: consistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results
• Good evidence: significant effects in one large or several mid-sized and well-designed clinical studies ( randomized controlled trialsa study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects with an appropriate placebo or other strong comparison control or observational studies that control for confounds)
• Modest evidence: significant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies), or several small studies aggregated into a meta-analysis
• Preliminary evidence: significant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect
• Weak evidence: one or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects
• Insufficient evidence: preclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example)

• No significant effect on body weight among people with cancer with low-carbohydrate ketogenic diets compared to any other diet in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 6 RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects of generally poor quality¹⁵Yang YF, Mattamel PB et al. Efficacy of low-carbohydrate ketogenic diet as an adjuvant cancer therapy: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2021 Apr 21;13(5):1388.
• No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on blood lipids among people with ovarian or endometrial cancer following a ketogenic diet (70% fat, 25% protein, 5% carbohydrate) compared to the American Cancer Society diet (high fiber and lower fat) for 12 weeks, with adherence 57–80%, in a small RCT¹⁶Cohen CW, Fontaine KR, Arend RC, Gower BA. A ketogenic diet is acceptable in women with ovarian and endometrial cancer and has no adverse effects on blood lipids: a randomized, controlled trial. Nutrition and Cancer. 2020;72(4):584-594.
• Lower weight, body mass index (BMI) and waist circumference among people with type 2 diabetes following a ketogenic diet compared to baseline in a meta-analysis of uncontrolled trialsa study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design¹⁷Yuan X, Wang J et al. Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis. Nutrition & Diabetes. 2020 Nov 30;10(1):38.
• Weight loss among people with advanced incurable cancers following a ketogenic diet (carbohydrates limited to 5% of total kilocalories) who achieved dietary ketosis compared to baseline in a small uncontrolled trial;¹⁸Fine EJ, Segal-Isaacson CJ et al. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition. 2012 Oct;28(10):1028-35.
• Slight increase in lean body mass among cachectic cancer patients following a ketogenic diet compared to baseline in a small uncontrolled trial¹⁹Fearon KC, Borland W et al. Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism. American Journal of Clinical Nutrition. 1988 Jan;47(1):42-8.
• Weight loss and lower body mass index (BMI), but no evidence of an effect on cholesterol or blood lipids among people with advanced metastatic tumors and no conventional therapeutic options following a ketogenic diet compared to baseline, but only 5 of 16 people were able to complete the 3-month intervention in a small uncontrolled study²⁰Schmidt M, Pfetzer N, Schwab M, Strauss I, Kammerer U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutrition & Metabolism. 2011 July 27;8(1):54.

• Worse appetite among people with advanced metastatic tumors and no conventional therapeutic options following a ketogenic diet compared to baseline, but only 5 of 16 people were able to complete the 3-month intervention in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design²¹Schmidt M, Pfetzer N, Schwab M, Strauss I, Kammerer U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutrition & Metabolism. 2011 July 27;8(1):54. Note: the people in this study were very ill from cancer, and 2 died during the study; symptoms such as these would likely have worsened either with or without the change in diet, but since the study was uncontrolled, we have no comparison group.

Preliminary evidence of better quality of life among people with cancer following a ketogenic diet

Weak evidence of worse physical function among people with advanced cancer following a ketogenic diet

• Better quality of life and mental health among people with stage 2 or 3 cancer with a modified ketogenic diet utilizing medium-chain triglyceride fats for 4 months compared to an institutionalized standard traditional diet in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²²Augustus E, Granderson I, Rocke KD. The impact of a ketogenic dietary intervention on the quality of life of stage II and III cancer patients: a randomized controlled trial in the Caribbean. Nutrition and Cancer. 2021;73(9):1590-1600.
• Stable quality of life and slightly worse physical function among people with advanced metastatic tumors and no conventional therapeutic options following a ketogenic diet compared to baseline, but only 5 of 16 people were able to complete the 3-month intervention in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design²³Schmidt M, Pfetzer N, Schwab M, Strauss I, Kammerer U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutrition & Metabolism. 2011 July 27;8(1):54. Note: the patients in this study were very ill from cancer, and 2 died during the study; symptoms such as these would likely have worsened either with or without the change in diet, but since the study was uncontrolled, we have no comparison group.

Preliminary evidence of low adherence and completion rates among people following a ketogenic diet

• Low rate of acceptance of the KD dietary restrictions by patients—only 37% of those on the KD were able to follow the diet for the duration of the study—in a review of clinical studies²⁴Erickson N, Boscheri A, Linke B, Huebner J. Systematic review: isocaloric ketogenic dietary regimes for cancer patients. Medical Oncology. 2017 May;34(5):72.
• Quality of life was a factor in decisions to decline participation in a trial which also had poor retention—only 4 of 12 patients completed the 3-month diet—among people with glioblastoma in a small RCT²⁵Martin-McGill KJ, Marson AG et al. Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study. Journal of Neuro-oncology. 2020 Mar;147(1):213-227.

• Less reported insomnia among people with advanced metastatic tumors and no conventional therapeutic options following a ketogenic diet compared to baseline, but only 5 of 16 people were able to complete the 3-month intervention in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design²⁶Schmidt M, Pfetzer N, Schwab M, Strauss I, Kammerer U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutrition & Metabolism. 2011 July 27;8(1):54.