Switching to a very strict low-carb diet was associated with an increase of systemic inflammation in apparently healthy subjects (Rosenbaum et al., 2019), while in subjects with metabolic syndrome or obesity, a short-term ketogenic diet yielded beneficial cardiometabolic effects (Gyorkos et al., 2019; Ruth et al., 2013). In T2DM patients, a one-year nutritional ketosis intervention resulted in a lower cardiovascular risk (Bhanpuri et al., 2018). Importantly, these beneficial effects are amplified by physical exercises (Alves et al., 2016; Asle Mohammadi Zadeh et al., 2018; Myette-Cote et al., 2018), and by the diet supplementation with nuts (Hou et al., 2018), soy (Kani et al., 2017), or even carefully choosing the types of ingested carbohydrates. In obese and overweight adolescents and adults, a diet based on low glycaemic index food improved inflammation, metabolic as well as cardiovascular risk factors (Rouhani et al., 2016), while the addition of functional foods resulted in further benefits (Izadi et al., 2018). Also, the consumption of complex carbohydrates led to a decline of pro-inflammatory molecules’ level in pregnant women (Hernandez et al., 2016). The results of most recent clinical studies concerning the link between low-carb diet and systemic inflammation are summarized in Table 3 . Table 3 Recent reports regarding the relationship between carbohydrate intake and inflammation. Diet type Design Population Intervention Effects Ref. Low-carbohydrate versus high-fat diet Randomized crossover study 11 T2DM patients 4-day diet intervention:➢ Group 1: Low-fat low-glycaemic index diet, ➢ Group 2: Low-carbohydrate high-fat diet ➢ Group 3: Low-carbohydrate high-fat diet +15-min postmeal walks Glycemia and circulating proinsulin were significantly lower in groups 2 and 3 versus 1; Myette-Cote et al. (2018) Low-carbohydrate versus low-fat diet Randomized controlled feeding study 33 obese T2DM patients 8-week diet intervention:➢ Normal diet ➢ Low-carbohydrate diet (LCD) ➢ Low-fat diet (LFD), ➢ followed by 12 weeks of high intensity interval training 3 days/week, then a 4-week diet intervention, as presented above. After the 24-week period:LCD: ↓ IL-6, resistin, leptin, glucose, insulin, cholesterol, TG, ↑ HDLLFD: ↓ TNF-α, LDL, HOMA-IR, ↑ adiponectin Asle Mohammadi Zadeh et al. (2018) Low-carbohydrate versus low-fat diet Randomised controlled trial 51 T2DM patients 6-month diet intervention:➢ Low-carbohydrate diet (LCD) ➢ Low-fat diet (LFD) LCD: ↓ sICAM, E-selectinLFD: ↓ CRP Davis et al. (2011) Low-carbohydrate versus low-fat diet Randomised controlled trial 51 T2DM patients 6-month diet intervention:➢ Low-carbohydrate diet (LCD) ➢ Low-fat diet (LFD) LCD: ↓ IL-1Ra, IL-6 Johansson-Persson et al. (2014) Low-carbohydrate versus low-fat diet Clinical trial 148 obese adults (no diabetes and CVD) 12-month diet intervention:➢ low-carbohydrate diet – LCD, n = 75 (<40 g/day) ➢ low-fat diet – LFD, n = 73 (<30% kcal/day from total fat, <7% saturated fat) LCD: ↑ adiponectin ↓ICAM Hu et al. (2015) Low-carbohydrate + nuts Randomised controlled trial 51 T2DM patients 3-month diet intervention:➢ Low-carbohydrate diet + peanuts: 60 g for men, 50 g for women (LCD-P) ➢ LCD + almonds: 55 g for men, 45 g for women (LCD-A) Improved glycaemic profile versus baseline, no difference between groups regarding IL-5 serum levels Hou et al. (2018) Low-Calorie, Low-Carbohydrate Soy Diet Parallel randomized clinical trial 45 patients with NAFLD 8-week diet intervention:➢ Group 1: Low-calorie (LC) diet, ➢ Group 2: LC, low-carbohydrate diet ➢ Group 3: LC, low-carbohydrate diet + soy (LCS) LCS: ↓ glycaemic indices, CRP Kani et al. (2017) Switching to an isocaloric ketogenic diet (KD) Clinical study 17 men (BMI: 25–35 kg/m2) Transitioning from a normal diet (4 weeks–35% fat, 15% protein, 50% carbohydrate) to 4 weeks of an isocaloric KD (80% fat, 5% carbohydrate, 15% protein) KD: ↑glycerol, free fatty acids, glucagon, adiponectin, gastric inhibitory peptide, TC, LDL, CRP↓Fasting insulin, C-peptide, triglycerides and fibroblast growth factor 21 Rosenbaum et al. (2019) Carbohydrate-restricted Paleolithic-based diet Randomized crossover trial 12 subjects with metabolic syndrome 4-week diet intervention:➢ carbohydrate-restricted (<50g) Paleolithic-based diet + sedentary activity (PD-S) ➢ PD + high-intensity interval training (PD-Ex) PD-S + PD-Ex: ↓ Glycaemia, TG, fasting insulin, insulin resistance, CRP, TNF-α, IL-6, ICAM-1 Gyorkos et al. (2019) Low carbohydrate high fat, diet Randomised controlled trial 55 obese subjects 12-week diet intervention:➢ High-fat, low-carbohydrate diet (HFLC) group ➢ Low-fat, high-carbohydrate diet (LFHC) group HFLC: ↓ CRP,TG ↑ adiponectin, HDL Ruth et al. (2013) Nutritional ketosis Randomised controlled trial 262 patients with T2DM 12-month diet intervention:➢ Nutritional ketosis (NK, n = 262) ➢ Control group, normal diet (n = 87) ↓ CRP Bhanpuri et al. (2018) Moderate-carbohydrate versus low-fat diet Randomised controlled trial 122 overweight and obese adults 6-month diet intervention:➢ Group 1: moderate-carbohydrate and high-glycaemic index (GI) diet (HGI), n = 37 ➢ Group 2: a moderate-carbohydrate and low-GI diet (LGI), n = 36 ➢ Group 3: a low-fat and high-GI diet (LF), n = 31 LGI vs LF: ↓ fasting insulin, ↑ HOMANo significant differences among groups regarding lipid profiles, inflammatory and metabolic risk markers (IL-6, MCP-1, Leptin, ICAM-1). Juanola-Falgarona et al. (2014) Low-glycemic-index diet Randomised controlled trial 90 subjects 12-week diet intervention:➢ isocaloric control diet (50% of energy from carbohydrate, 35% from fat, 15% from protein) ➢ low-glycaemic-index diet (LGI) (60% from carbohydrate, 25% from fat, and 15% from protein) ➢ LGI, rich in functional foods (LGI + FF) (60% from carbohydrate, 25% from fat, and 15% from protein) LGI + FF vs. control: ↓CRP, TNF-αLGI + FF vs. LGI: ↑ adiponectin Izadi et al. (2018) Low glycaemic index diet Randomised controlled trial 50 obese and overweight adolescent girls 10-week diet intervention:➢ Healthy nutritional recommendation diet (HNR) ➢ Low glycaemic index diet (LGI) ↓ IL-6, CRP Rouhani et al. (2016) Low- carbohydrate high-fat diet versus higher-complex carbohydrate lower-fat Randomized controlled feeding study 12 overweight and obese women with gestational (31 weeks) diabetes mellitus 31-week diet intervention:➢ control conventional low-carbohydrate, higher-fat diet (LCHF, 40% carbohydrate, 45% fat, 15% protein; n = 6) ➢ higher-complex carbohydrate/lower-fat diet (CHOICE, 60% carbohydrate, 25% fat, 15% protein; n = 6) CHOICE: ↓ expression of proinflammatory genes (IL-1β, TNF- α) Hernandez et al. (2016) Regular diet Observational study 95 postmenopausal women Participants classified according to CRP - lower or ≥3 mg/L. Sedentary lifestyle was described by walking ≤6000 steps/day; diet was evaluated using a validated food frequency questionnaire. CRP was higher for women with sedentary lifestyle and higher glycaemic load Alves et al. (2016) Low-fructose diet Comparative study 28 patients with chronic kidney disease 6-week of low-fructose diet (LFD), followed by 6 weeks of regular diet ↓ insulin, CRP sICAM (decrease of insulin and sICAM persistent, while CRP did not when resuming regular diet) Brymora et al. (2012) ICAM – intercellular adhesion molecule-1; HOMA – homeostatic model assessment of β cell function; MCP-1 – Monocyte chemotactic protein-1.