Table 1.

Summary of Clinical Studies of KD and Cancer.

Cancer Type(s)	Sample Size	Dietary Intervention	Study Duration	Results/Outcomes	References
Prostate	N = 45 Arm A: N = 27 Arm B: N = 18	Arm A: A low-carbohydrate diet, goal: (≤20 g per day), estimated actual carbohydrate intake: 37 g/day; Arm B: Control group (no dietary intervention)	6 months	-Weight loss -BMI reduction -Waist circumference reduction	[51]
Breast cancer	N = 60 Arm A: N = 30 Arm B: N = 30	Arm A: Medium-chain triglycerides (MCT) based ketogenic diet (6% calories from Carbohydrates [CHO], 19% protein, 20% MCT, 55% fat); Patients received 500 mL of MCT oil from the Nutricia Company every 2 weeks Arm B: Standard Diet (55% CHO, 15% protein, and 30% fat)	3 months	-Weight loss -BMI reduction -Reduction in body fat	[52]
Ovarian/endometrial cancer	N = 45 Arm A: N = 25 Arm B: N = 20	Arm A: Ketogenic diet (70% (≥125 g): 25% (≤100 g): 5% (<20 g) energy per day from fat, protein, and carbohydrates) Arm B: American Cancer Society diet (ACS: high in fiber, low in fat) Individual diet advice from certified dietitians. Weekly emails or phone calls. One face-to-face meeting after baseline assessment	3 months	-Self-reported improvement in energy levels (intervention group) -Fewer cravings for starchy foods and fast-food fats -Reduction in total body	[53,54]
Rectal cancer, head and neck cancer Breast cancer	N = 81 Arm A: N = 20 Arm B: N = 61	Arm A: ketogenic diet with additional consumption of non-glucogenic amino acids Arm B: no dietary intervention	30–40 days	-Decreased fat mass	[55]
Pancreatic cancer Duodenal cancer Common bile duct cancer Ampulla of Vater cancer Cholangiocarcinoma Neuroendocrine tumor	N = 19 Arm A: N = 10 Arm B: N = 9	Arm A: Ketogenic diet (3–6%, 14–27%; 70–80% energy per day from carbohydrates, protein, and fat) served as three meals and three snacks per day Arm B: usual Korean diet (55–65%, 7–20%, 15–30% energy per day from carbohydrates, protein and fat) served as three meals per day	12 days	-Decreased body cell mass higher in General Diet arm	[56]
Glioblastoma multiforme	N = 53 Arm A: N = 6 Arm B: N = 47	Arm A: self-administered KD Arm B: unspecified standard American diet	Duration: 3–12 months	- Two patients with grade 1 constipation, 4 patients with grade 1 fatigue, 1 patient with grade 2 fatigue, 1 patient with deep venous thrombosis during treatment, 1 patient with asymptomatic hypoglycemia, 1 patient with nephrolithiasis no grade 3 and higher toxicities or symptomatic hypoglycemia -Weight loss on non-calorie-restricted KD: 1 to 27 Ibs -Weight loss on calorie-restricted KD: 46 Ibs	[57]
Fearon et al. [44] Ovarian, Lung, Gastric	N = 5	Crossover study: Nasogastric tube feeding: normal, balanced regimen on days 1–6 KD containing same total calorie and protein on days 7–13	13 days	-Increase in body weight	[58]
Diverse	Recruited patients N = 12 Analyzed patients N = 10	KD with targeted CHO intake below 5% of total energy intake, written menus and samples of CHO-restriction products were provided	28 days	-Five patients with grade 2 fatigue, 5 patients with grade 1 constipation, 1 patient with grade 1 leg cramps -Weight loss - Decreased caloric intake -Adherence: 5 of 12 patients completed all 28 days of the diet	[27]
Diverse	Analyzed patients N = 78 Arm A: N = 7 Arm B: N = 6 Arm C: N = 65	Arm A: full adoption of a non-specified KD, patients informed about a single company producing KD-related food Arm B: partial adoption of a non-specified KD, patients informed about a single company producing KD related food Arm C: patients who did not adopt a KD	Not specified	1. Reduction in TKTL 1 was associated with adopting a KD; 2. Correlation between improvement in cancer status category and full adoption of a KD (χ2 = 33.26; df = 4; p = 0.00001	[59]
Diverse	Analyzed patients N = 6	Self-administered KD (recommended CHO intake < 50 g/day) during the course of RT/RCT; patients received basic information on KD; counseling at least once per week	Patient-dependent from 32 to 73 days	-Decreased fat mass	[60]
Glioblastoma	Assessed for eligibility: N = 57 Randomized: N = 12 Arm A: N = 6 Arm B: N = 6 Retention at 12 weeks. N = 4 Arm A: N = 3 Arm B: N = 1	Arm A: MCTKD (75%; 15%; 10% of energy per day from fat, protein and carbohydrates, with 30% of fat from MCT nutritional products) Arm B: MKD (80%; 15%; 5% of energy per day from fat, protein and carbohydrates)	12 weeks	1. Arm A: Three patients retained for 3 months (drop-out = 50%) Arm B: One patient retained for 3 months (drop-out = 83%) 2. GHS at baseline: Arm A: patients who later withdrew: 72.2 ± 20.7; patients who retained: 75 ± 6.8 Arm B: patients who later withdrew: 70 ± 13.8; patients who retained: 80 ± 0 GHS: at week 6: Arm A: patients who withdrew at week 6: 41.7 ± 0; patients who retained: 66.7 ± 0 Arm B: patients who withdrew at week 6: 50 ± 0; patients who retained: 100 ± 0 3. Adverse events during the first 6 weeks: Arm A: diarrhea (n = 1, CTCAE grade 1), nausea (n = 1, CTCAE grade 1), vomiting (n = 1, CTCAE grade 2), dyspepsia (n = 1, CTCAE grade 1) Arm B: vomiting (n = 1, CTCAE grade 1), dry mouth (n = 1 MKD, CTCAE grade 1)	[61]
Glioblastoma	Enrolled: N = 6 Completed intervention: N = 4	MKD (70%: 3–5% (≤20 g) energy per day from fat and carbohydrates; protein consumption was not restricted	12 weeks	-Constipation in two patients, resolved with dietary modification	[62]
Glioblastoma	Included patients N = 20 Evaluable for efficiency N = 17	KD with CO intake < 60 g/day, additionally highly fermented yoghurt drinks and two different plant oils were provided to be consumed at will. No calorie restriction, patients were instructed to always eat to satiety	Until progression of the disease	-Three out of 20 patients discontinued the diet after 2–3 weeks without progression, due to reduced QoL - Body weight reduction -Diarrhea, constipation, hunger and/or demand for glucose were present in some patients during the diet	[63]
Diverse	Enrolled: N = 16 Completed intervention: N = 5	KD with CHO limited to 70 g per day and 20 g per meal Two oil–protein shakes consumed in the morning and in the afternoon	12 weeks	-11/16 Patients discontinued the diet - 3/11 were unable to adhere to the diet, -6/11 discontinued due to progressive disease -2/11 died from progressive disease - reported side effects included increase in appetite loss, constipation, diarrhea and fatigue during the diet - QoL was low at baseline and stayed relatively stable during the intervention; worsening of fatigue, pain, dyspnea and role function but emotional functioning and insomnia improved slightly	[64]
Diverse	Enrolled: N = 17 Drop-out before first analysis: N = 6 Completed intervention: N = 4	Modified Atkins Diet with 20 to 40 g of CHO and restricted consumption of high CHO foods no restrictions for calories, protein or fats	16 weeks	-13/17 patients discontinued the diet before 16 weeks -weight loss -Reported adverse effects included: hyperuricemia (N = 7), hyperlipidemia (N = 2), pedal edema (N = 2), anemia (N = 2), halitosis (N = 2), pruritus (N = 2), hypoglycemia (N = 2), hyperkalemia (N = 2), hypokalemia (N = 2), hypomagnesemia (N = 2), flulike symptoms/fatigue (N = 2)	[65]
Glioblastoma multiforme	Phase A: N = 9 Phase B: N = 8 Completed intervention N = 6	Phase A: Fluid KD with a 4:1 ratio (4 g fat versus 1 g protein plus carbohydrates, 90% energy from fat) Patients were allowed a snack with the same 4:1 diet ratio once a day Phase B: Solid-food KD (diet ratio 1.5–2.0:1) with MCT; (70% energy from fat with the consistency of an emulsion)	14 weeks	-6/9 patients included in phase A completed the 14 weeks KD - Reported adverse effects included: constipation (n = 7), nausea/vomiting (n = 2), hypercholesterolemia (n = 1), hypoglycemia (n = 1), low carnitine (n = 1) and diarrhea (n = 1). CTCAE grade 2: hallucinations (n = 1), allergic reaction (n = 1) and wound infection (n = 1)	[66]
Glioma	N = 29	MAD with a 0.8–1:1 ratio (0.8-1 g fat to 1 g carbohydrate plus protein Duration: 6 weeks	6 weeks	-28/29 patients completed the 6-week diet - Reported adverse events: Grade 2 constipation (n = 1), grade 1 fatigue and nausea were present in the patients -Decreased BMI for all patients	[67]
Lung	Enrolled patients: N = 7 Completed intervention: N = 2	KD with 90%; 8%; 2% of energy per day from fat, protein and carbohydrates. All meals prepared for the patients	42 days	-Weight loss - Reported adverse events included: constipation, diarrhea, nausea, vomiting and fatigue; hyperuricemia	[68]
Pancreas	N = 2	KD with 90%; 8%; 2% of energy per day from fat, protein and carbohydrates. All meals readily prepared for the patients	34 days	-1/2 patients completed the intervention 2. Reported adverse events included: Constipation, diarrhea, nausea and vomiting, 1 patient experienced dehydration -Weight loss	[68]
Desmoid tumor	N = 1	TPN consisting of 28 kcal fat/kg body weight/day, 1.5 g protein/kg body weight/day; 40 g glucose/day	Desmoid tumor	-Body weight increased	[69]
Glioma	N = 2	ERKD: with a 3:1 ratio of ingested nutrients (3 g fat versus 1 g protein plus carbohydrates) 20% restriction of calories per day	12 months	-Adherence: 1/2 patients completed the intervention -Reported headaches -Initial body weight decrease in both patients and remained stable afterward	[70]
Glioblastoma multiforme	N = 1	ERKD delivering 600 kcal per day, consisting of 42 g fat, 32 g protein and 10 g CHO per day	56 days	-Bodyweight decreased in the first 14 days of the diet - Grade 4 hyperuricemia reported, resulted in diet change to calorie restricted non-ketogenic diet	[71]
Rectal	N = 1	Paleolithic KD, nutrients consumed in a fat:protein ratio of 2:1 animal fat, red meats and organ meats were encouraged, root vegetables were allowed, all other foods were prohibited	24 months	-Decreased bodyweight -Initial decrease in volume after concomitant radiotherapy -Tumor volume remained stable but four hepatic metastases were detected at the end of the diet	[72]
Diverse	N = 12	Single 3 h infusion of glucose-based (GTPN) or a lipid-based TPN (LTPN) containing 4 mg glucose/kg/min or 2 mg lipid/kg/min, respectively	3 h	-No statistically significant stimulation or suppression of FDG uptake	[73]
Recurrent Breast	N = 1	Self-administered high doses of oral vitamin D3 (10,000 IU/day), and KD rich in oleic acid. Duration: 3 weeks	3 weeks	-Progesterone receptor status positivity increased -HER2 positivity decreased	[74]
Astrocytoma	N = 2	KD with 60%; 20%; 10%, 10% of energy per day from MCT oil, protein, carbohydrates and dietary fat plus additional supplements	8 weeks	-Dose uptake ratio tumor: decreased normal cortex decreased -Adherence: 100% patients were able to complete the dietary intervention	[75]
Esophagus Stomach Colon-rectum	N = 27 Arm A: N = 9 Arm B: N = 9 Arm C: N = 9	Arm A: glucose-based TPN (100% of the calorie from dextrose); Arm B: lipid-based TPN (80% of the calorie from fat, 20% from dextrose); Arm C: oral diet All diets were iso-caloric and isonitrogenous. Duration: 2 weeks	2 weeks	No statistically significant changes	[76]
Head and neck	N = 12	Unspecified Western diet followed by unspecified KD	Variable, up to 4 days	Decline of mean lactate concentration in the tumor tissue during the KD	[77]
Brain	Included: N = 9 intervention: N = 5 retrospectively added control N = 4	KD based on ready-made formula, with a 4:1 ratio of ingested nutrients (4 g fat versus 1 g protein plus carbohydrates)	variable from 2 to 31 months	-Diet tolerated by 4/5 patients,(strict adherence only in 2 patients) -Four out of 50 MRI spectroscopy scans detected ketone bodies in the brains of the patients following the KD	[78]
Lung	N = 44	Mild KD (patients were encouraged to avoid high CHO food) in combination with HBO, hyperthermia and polychemotherapy administered during induced hypoglycemia	24 weeks	-Adverse events reported—during treatment period: grade 5 neutropenia (N = 1), grade 3 neutropenia (N = 3), grade 3 anemia (N = 10), grade 4 thrombocytopenia (N = 3), grade 3 fatigue (N = 5), grade 3 diarrhea (N = 8), grade 3 neuropathy (N = 1), all of which were attributed to chemotherapy	[79]
Pancreas	N = 25	Mild KD (patients were encouraged to avoid high CHO food) in combination with HBO, hyperthermia and polychemotherapy administered during induced hypoglycemia	Duration: mean follow-up: 25 months	-Adverse events reported: during treatment period: grade 3/4 neutropenia (N = 9), febrile neutropenia (N = 1), grade 3 anemia (N = 7), grade 4 thrombocytopenia (N = 4), grade 3 diarrhea (N = 2), all of which were attributed to chemotherapy	[80]
Brain	N = 8	MAD with20g CHO/day restriction	2-24 months: mean- 13 months	-7/8 completed intervention -Decreased body weight -Reduction in seizure frequency per week	[81]
Glioblastoma multiforme	N = 1	Energy-restricted KD with a 4:1 ratio of calorie intake (fat versus protein plus carbohydrates) Total calories calculated 25% below BMR	4 months	-No metabolically active tumor detected	[82]
Glioblastoma multiforme	N = 1	KD with a 4:1 ratio of calorie intake (fat versus protein plus carbohydrates), delivered as calorie-restricted diet, combined with intermittent fasting, HBOT, other novel therapies and SOC treatment	20 months	-Good surgical outcome and regressive changes in histopathology -Decreased body weight	[83]
Diverse	N = 6	Very low CHO diet (not further specified) with a multitude of supplements, including amino acids and Vitamin D3 combined with SOC therapy	Varied	-Shrinkage of tumor or stable disease was reported during the intervention -Subjective improvement reported in some cases	[84]
Head and neck	N = 14	KD with as little CHO as possible (estimated < 50 g per day), combined with insulin administration 3 × per day	Not specified	Visible remission after 2–3 weeks, but rebound effect after 2–3 months on the diet	[85]
Extra-cranial	N = 30	KD with as little CHO as possible (estimated < 50 g per day), combined with insulin administration 3 × per day	Not specified	Tumor shrinkage in some cases Improvement in general condition and positive effects on clinical symptoms	[86]
Exra-cranial	N = 23	KD with as little CHO as possible (estimated < 50 g per day), combined with insulin administration 3 × per day	Not specified	-Reduced pain severity, fatigue but deteriorated orientation	[87]
Pancreatic cancer Duodenal cancer Common bile duct cancer Ampulla of Vater cancer Neuroendocrine tumor	N = 18	LCKD: Energy content: 1500 kcal/d, provided 4% from carbohydrate, 16% from protein and 80% from fat. Ketogenic ratio of 1.75:1 (F: C + P w/w)	4 weeks	-Patients were in a poorer nutrition state after surgery, but this was alleviated at week 4; - LCKD induced ketone body production -Week 4, there were no significant differences in ketone levels	[88]
Glioma	N = 13 newly diagnosed= 6 recurrent=7	KD + MCT + Metformin 850	6 weeks (recurrent) 2 weeks (newly diagnosed)	Increase in survival rate. Synergistic interaction between radiation therapy and KD.	[89]
Invasive Rectal	N = 359	KD ≥ 40% kcal fat and <100 g/day glycemic load (48)	Not specified	Reduced risk of cancer-specific deaths	[90]
Glioblastoma	N = 32	KD 50% kcal fat, 25% kcal CHO, 1.5 g/kg protein (17), CD (15)	3 months	No change in glucose increased ketosis No change in body weight	[91]