Background: many patients who struggle to lose weight are unable to cut down certain ultra-processed, refined types of food with a high glycemic index. This condition is linked to responses similar to addiction that lead to overeating. A very-low-calorie ketogenic diet (VLCKD) with adequate protein intake could be considered a valid dietary approach. The aim of the present study was to evaluate the feasibility of a VLCKD in women with binge eating and/or food addiction symptoms. Methods: subjects diagnosed with binge eating and/or food addiction symptoms (measured with the Binge Eating Scale and the Yale Food Addiction Scale 2.0) were asked to follow a VLCKD with protein replacement for 5–7 weeks (T1) and a low-calorie diet for 11–21 weeks (T2). Self-reported food addiction and binge eating symptoms and body composition were tested at T0 (baseline) and at the end of each diet (T1 and T2 respectively); Results: five women were included in the study. Mean age was 36.4 years (SEM = 4.95) and mean BMI was 31.16 (SEM = 0.91). At T0, two cases of severe food addiction, one case of mild food addiction, one case of binge eating with severe food addiction, and one case of binge eating were recorded. Weight loss was recorded at both T1 and T2 (ranging from 4.8% to 11.6% of the initial body weight at T1 and from 7.3% to 12.8% at T2). No case of food addiction and/or binge eating symptoms was recorded at T2. Muscle mass was preserved. Conclusions: recent findings have highlighted the potential therapeutic role of ketogenic diets for the treatment of addiction to high-calorie, ultra-processed and high-glycemic food. Our pilot study demonstrates the feasibility of a ketogenic diet in women with addictive-like eating disorders seeking to lose weight.

Introduction Chronic pain is related to gastrointestinal (GI) functions because food components affect inflammation and pain through their action on the GI immune and/or neural system and because many analgesics interact with the gut to alter its structure and function. Immunoglobulin G4 (IgG4) are food-specific antibodies resulting from exposure of the gut immune system to nutrients. High IgG4 levels have been found to be associated with inflammation. Methods IgG4 were determined (both with the rapid test and enzyme-linked immunosorbent assay, ELISA) in men and women outpatients with chronic pain. All subjects were asked to exclude for 4 weeks all foods to which they had high blood levels of IgG4 antibodies. Pain and quality of life questionnaires were administered before (visit 1) and after (visit 2) the personalized exclusion diet period. Visual analogue scale (VAS), Italian Pain Questionnaire (QUID) and Margolis (MA) questionnaires were administered to determine pain intensity, pain features and pain extent, while Short Form Health Survey (SF-36) and Profile of Mood States (POMS) were used to test the quality of life and mood state. The nutritional status was evaluated in all subjects. Subject groups were women of reproductive age (pre-MW), women in menopause for at least 1 year (MW) and men. Results Fifty-four subjects with chronic pain (n = 12 neuropathic, n = 14 diffuse pain, n = 11 headache, n = 17 low back pain) completed the two visits and the 1-month exclusion diet. At visit 1, 47 (87%) subjects showed medium/high levels of IgG4 to at least one food. The foods showing the highest IgG4 values were eggs, dairy products, cereals and dried fruit. At visit 2, IgG4 levels were decreased, increased or unchanged. In all groups, the 4-week exclusion diet resulted in a significant reduction in all pain measures and an improvement of quality of life parameters. In particular, at visit 2, the VAS score determined in the morning decreased by more than 50%. Conclusions A food elimination diet based on IgG4 antibody levels may be effective in reducing pain and improving quality of life in patients with chronic pain.

Fibromyalgia (FM) is a common chronic disorder with chronic pain. FM generally affects all ages and occurs more commonly in women. The cause of FM remains undefined, but a number of factors suggest the cardiovascular system and the blood in particular as contributors to its occurrence and maintenance. Hemograms and other blood indexes often show high percentages of values at the ‘normal’, low, or high limits and several values outside of the ‘normal’ ranges. On the other hand, vessels regulate blood arrival to tissues depending on many internal and external factors. Both aspects can interfere with tissue oxygenation and then with the numerous consequences induced by hypoxia. In this narrative review, efforts were made to highlight factors that are potentially able to affect oxygen arrival in cells, as well as other factors related to blood elements that can play a role in the chronic pain experienced by FM patients. Data strongly indicate that most of the symptoms commonly present in FM patients can find their physio-pathological basis in the blood, suggesting blood-related interventions in these patients.

Pain is a chronic condition in many women; drugs used for its treatment are often accompanied by detrimental effects on many organs, including the gut. Once inflamed, the gut can affect pain processes. The aim of this study was to evaluate the general health of women suffering chronic pain, with particular attention to gastrointestinal (GI) conditions. The possibility to improve pain and quality of life through personalized nutritional advice was also tested. Forty women suffering from chronic pain were contacted for the administration of questionnaires to define their pain features and gastrointestinal conditions. Their psychological, clinical and reproductive states were also recorded. Pain scores were correlated with GI, psychological and clinical scores. Diet suggestions were given, and evaluation was repeated after 4 weeks. Thirty-eight women were included in the study: 32 suffered chronic widespread pain and had 6 pelvic pain. Pain had been present in all women for years; more than 80% of women reported various types of disorders related to the gut. Pain scores were worse in the women intolerant to milk and dairy products. The GI score was positively correlated with the pain score. The Dietary Inflammatory Index was very high in all subjects. Personalized nutritional advice followed by 26 subjects for 4 weeks resulted in a significant improvement of pain and quality of life parameters. We describe women with chronic pain as being particularly affected by GI alterations. The change in feeding habits had a beneficial effect on pain and other quality of life parameters.

Free fatty acid receptor 1 (FFAR1) has emerged as the most targeted isoform of the free fatty acid receptors because of its involvement in the modulation of energy balance and its potential role in the control of inflammatory and pain conditions. Quercetin-3-oleate (AV2), recognized as a new FFAR1 partial agonist, was investigated for its ability to modulate inflammation and nociception. Human immortal neuroblastoma SH and the murine macrophagic RAW 264.7 cells were used to evaluate cell viability, the potential cytoprotective activity, and the anti-inflammatory properties of AV2 in vitro. Paw edema, caused by zymosan-A, and the formalin test were used to assess the in vivo anti-inflammatory and antinociceptive effects in CD-1 mice. In vitro, AV2 was devoid of cytotoxicity, significantly reduced ROS in both cell types, and protected RAW 264.7 cells from lipopolysaccharide damage by reducing tumor necrosis factor-α production. Interestingly, AV2 induced a transient elevation of intracellular calcium that was reduced in cells, pre-incubated with the FFAR1 antagonist DC260126. In vivo, AV2 reduced formalin-induced nociception and zymosan A-induced paw edema, and both effects were reversed by the FFAR1 antagonist GW1100. In conclusion, these data strongly support the AV2-mediated antioxidant, anti-inflammatory, and antinociceptive activity. AV2 represents a promising molecule for the clinical management of inflammatory-related pain conditions.

Background: Piperine, an alkaloid from Piper nigrum, modulates oxidative stress, proliferation, and survival pathways in several cancer models; however, its mechanistic effects in colorectal epithelial Caco-2 cells remain insufficiently defined. Objective: This study aimed to investigate the cytotoxic, antiproliferative, oxidative, autophagic, and anti-migratory effects of piperine in Caco-2 cells. Methods: Caco-2 cells were treated with piperine (0.001–0.1 mg/mL) for up to 72 h. Cell viability, proliferation, and migration were assessed using SRB and scratch assays. Oxidative stress, apoptosis, autophagy, and tight junction integrity were evaluated through ROS quantification, Western blotting, gene expression analysis, confocal microscopy, and transmission electron microscopy (TEM). NACET was used to determine the contribution of oxidative stress to piperine-induced cytotoxicity and autophagy. Results: Piperine induced a time- and dose-dependent reduction in viability, with viability decreasing to 53.0 ± 2.88% at 0.1 mg/mL after 72 h. Proliferation decreased to 51% of control levels (p < 0.001), accompanied by p21 upregulation (p < 0.05), indicating G2/M cell cycle arrest. Piperine markedly increased intracellular ROS (p < 0.001), downregulated NRF2 (p < 0.05), and suppressed GSTA1 expression (p < 0.001), while NACET co-treatment restored viability (p < 0.001). No activation of caspase-dependent apoptosis was observed. Piperine significantly enhanced autophagic flux, as shown by the increased LC3B-II/LC3B-I ratio (p < 0.01), elevated LC3B-II/LAMP-1 co-localization (p < 0.01), and chloroquine-induced accumulation of LC3B-II and p62 (p < 0.01), with preserved lysosomal function. TEM analysis confirmed a marked increase in double-membrane autophagosomes in piperine-treated cells compared with controls. NACET reduced LC3B-II/LC3B-I levels, increased p21 expression, and significantly improved cell viability, indicating that piperine-induced autophagy is cytotoxic and driven by oxidative stress. Additionally, piperine upregulated occludin (p < 0.01) and reduced cell migration independently of proliferation (p < 0.01). Conclusions: Piperine exerts antiproliferative effects in Caco-2 cells through ROS-mediated stress, p21-dependent G2/M arrest, and activation of cytotoxic autophagy. Its ability to impair migration and enhance tight junction integrity further supports its potential as a complementary therapeutic agent in colon cancer.