Table 4.

Combined intervention results

Reference (author, year)	Design	Population (No. of participants, age, site/lesion type)	Intervention (DR intervention, corresponding cancer treatment)	Feasibility	Tolerance	Treatment effect
Freedland, 2016, USA [44]	RCT	40 (19 IG, 21 CG) Age NR Prostate cancer	Low CHO diet (< 20 g/day) combined with moderate physical activity increased by 30 min/day for 5 days/wk. Concurrent to ADT	81% retention	Mild headaches main side effect	↓ HOMA by 19% in IG compared to 7% in CG (p = 0.127) at 3 m ↓ weight (kg) of 9.3 in IG compared to ↑ of 1.3 in CG (p < 0.001) at 6 m ↓ FM of 16.2% in IG compared to ↑ of 11.0% in CG (p = 0.002) at 6 m ↑ bone mineral content of 0.1% in IG compared to ↓2.3% in CG (p = 0.025) at 6 m ↓ PSA 99% in both groups (p = 0.37)
Reinwald, 2015 and Branca, [45], Italy [46]	Case report	1 Age 66y Breast cancer	An isocaloric KD: special amino acid formula combined with probiotic yoghurt containing vitD binding protein macrophage activating factors and injections of vitD, oleic acid and vitD binding protein 3 weeks prior to surgery	NR	NR	Change in gene expression to HER2 -ve. Increase in progesterone expression (20 vs < 1%) No invasion of blood or lymph vessels around the tumour ER and Ki-67 markers were unchanged
Iyikesici, 2017, Turkey [47]	Case report	1 Age 29y Triple negative breast cancer	Chemotherapy administered after a 12 h fast followed by 5–10 units of insulin. Patient also consumed a KD for duration of treatment	Patient adhered to KD (urinary ketones present at each visit)	NR	Pathological complete response
Zuccoli, 2010, Italy [48]	Case report	1 Age 65y Brain cancer	Self-administered post-operative fast followed by a calorie restricted KD with chemo-radiotherapy. KD: 600ckal/day using Keto-Cal® 4:1 supplemented with multivitamins. After approx. 2 months on restricted KD, patient switched to a calorie restricted non-KD (600 kcal/day) for 5 months.	NR	Karnofsky performance status: 100% during diet Hyperuricemia on restricted KD so patient was switched to a non-KD calorie restricted diet. Hypoproteinemia on restricted diet, resolved by increasing dietary protein to 7 g/day for 1 month. ↓ bodyweight (− 9%) after fast and − 22% after restricted diet	↓ blood glucose: −50% after fast and − 53.3% after restricted diet ↑ ketones: from 0 (baseline) to 2.5 mmol/L after fast and after restricted diet

↑ = increase

↓ = reduction

Where absolute figures were provided, %s have been calculated to aid comparison

Abbreviations: ADT Androgen Deprivation Therapy, CG Control Group, CHO Carbohydrate, DR Dietary Restriction, ER Estrogen receptor, FM Fat Mass, HER-2 Human Epidermal Growth Factor Receptor 2, HOMA Homeostatic model assessment, IG Intervention Group, KD Ketogenic Diet, m months, NR Not Reported, PSA Prostate-Specific Antigen, RCT Randomised Controlled Trial, VitD Vitamin D