The obesity paradox refers to extant evidence showing that obesity in older subjects or in patients with several chronic diseases may be protective and associated with decreased mortality. A number of mechanisms have been postulated to support the existence of obesity paradox; however, marked heterogeneity was found across studies and this has cast doubt on the actual presence of this phenomenon. The aim of the present narrative review is to summarize evidence underlying the concept of obesity paradox, focusing on limitations and bias related to this phenomenon, with emphasis on the use of body mass index (BMI). A major cause of the discrepancy between studies may be related to the use of BMI in the definition of obesity, that should consider, instead, excess body fat as the main characteristic of this disease and as the unique determinant of its complications. In addition, the adjustment for potential confounders (e.g., stage and grade of diseases, smoking habit, inability to capture the presence of signs of undernutrition in the normal-weight comparative group, consideration of body composition) may significantly scale down the protective role of obesity in terms of mortality. However, it is still necessary to acknowledge few biases (e.g., reverse causation, attrition bias, selection bias of healthy obese subjects or resilient survivors) that would still apply to obesity even when defined according with body composition. Further research should be prompted in order to promote correct phenotyping of patients in order to capture properly the trajectories of mortality in a number of diseases.

The ketogenic diet, originally developed for the treatment of epilepsy in non-responder children, is spreading to be used in the treatment of many diseases, including Alzheimer’s disease. The main activity of the ketogenic diet has been related to improved mitochondrial function and decreased oxidative stress. B-Hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species (ROS), improving mitochondrial respiration: it stimulates the cellular endogenous antioxidant system with the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), it modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD⁺/NADH) and it increases the efficiency of electron transport chain through the expression of uncoupling proteins. Furthermore, the ketogenic diet performs anti-inflammatory activity by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome as well as inhibiting histone deacetylases (HDACs), improving memory encoding. The underlying mechanisms and the perspectives for the treatment of Alzheimer’s disease are discussed.

To assess the impact of a personalized diet, with or without addition of VSL#3 preparation, on biomarkers of inflammation, nutrition, oxidative stress and intestinal microbiota in 62 healthy persons aged 65-85 years. Open label, randomized, multicenter study. High-sensitivity C-reactive protein. Community. Eight week web-based dietary advice (RISTOMED platform) alone or with supplementation of VSL#3 (2 capsules per day). The RISTOMED diet was optimized to reduce inflammation and oxidative stress. Blood and stool samples were collected on days 1 and 56. Diet alone reduced ESR (p = 0.02), plasma levels of cholesterol (p < 0.01) and glucose (p = 0.03). Addition of VSL#3 reduced ESR (p = 0.05) and improved folate (p = 0.007), vitamin B12 (p = 0.001) and homocysteine (p < 0.001) plasma levels. Neither intervention demonstrated any further effects on inflammation. Subgroup analysis showed 40 participants without signs of low-grade inflammation (hsCRP<3 mg/l, subgroup 1) and 21 participants with low-grade inflammation at baseline (hsCRP≥3 mg/l, subgroup 2). In subgroup 2 addition of VSL#3 increased bifidobacteria (p = 0.005) in more participants and improved both folate (p = 0.015) and vitamin B12 (p = 0.035) levels compared with subgroup 1. The increases were positively correlated to the change in the bifidobacteria concentration for folate (p = 0.023) and vitamin B12 (p = 0.001). As expected change in homocysteine correlated negatively to change in folate (r = -0.629, p = 0.002) and vitamin B12 (r = -0.482, p = 0.026). Addition of VSL#3 increased bifidobacteria and supported adequate folate and vitamin B12 concentrations in subjects with low-grade inflammation. Decrease in homocysteine with VSL#3 was clinically relevant. suggesting protective potentials for aging-associated conditions, e.g. cardiovascular or neurological diseases. ClinicalTrials.gov: NCT01069445-NCT01179789.

To evaluate the change in eating habits occurring in community- dwelling and institutionalized elderly subjects with senile anorexia. Cross- sectional, observational. Community, nursing homes and rehabilitation or acute care facilities in four Italian regions. A random sample of 526 subjects, aged 65 years and older (217 free living individuals, 213 residents in nursing homes, and 93 patients in rehabilitation and acute wards). All subjects underwent a multidimensional geriatric evaluation of: nutritional status, anthropometric parameters, health and cognitive status, depression, taste, chewing and swallowing function, and some hormones related to appetite. Diet variety was assessed, considering the frequency of consumption of different food groups (milk and dairy products; meat, fish, and eggs; cereals and derivatives; fruit and vegetables). In anorexic elderly subjects the global food intake was reduced, and the eating pattern was characterized by the reduced consumption of certain food groups (“meat, eggs and fish” and “fruit and vegetables”) whereas the frequency of consumption of milk and cereals remained almost unchanged. Nutritional parameters were significantly better in normal eating subjects and correlated with diet variety. Because of the high prevalence of senile anorexia in the geriatric population and its impact on the nutritional status, further research should be prompted to establish an intervention. protocol allowing the early diagnosis of anorexia of aging, aimed at identifying its causes and at optimizing treatment of anorexic patients.

The Mediterranean diet (MD) has been proposed as a healthy dietary pattern for disease prevention. However, little information exists on the cost and on the environmental impact of such a dietary model. We compared the environmental impact and the costs of the current food consumption pattern of the Italian population and the Mediterranean model in order to investigate its overall sustainability. The environmental impact was calculated on the basis of three indexes, i.e. Carbon, Ecological and Water Footprint. The costs (Euro) per person of the MD and of the current Italian household food expenditure were considered on a weekly basis according to the 2013 data from the Observatory prices and tariffs of the Ministry of Economic Development and the service SMS consumers of the Ministry of Agriculture, Food and Forestry. The MD resulted to produce a lower environmental impact than the current food consumption of the Italian population. The monthly expenditure of the MD is slightly higher in the overall budget compared to the current expenditure allocated to food by the Italian population, but there is a substantial difference in the distribution of budget according to the different food groups.

Here we aimed at determining the therapeutic effect of a very low-calorie diet in overweight episodic migraine patients during a weight-loss intervention in which subjects alternated randomly between a very low-calorie ketogenic diet (VLCKD) and a very low-calorie non-ketogenic diet (VLCnKD) each for one month. In a nutritional program, 35 overweight obese migraine sufferers were allocated blindly to 1-month successive VLCKD or VLCnKD in random order (VLCKD-VLCnKD or VLCnKD-VLCD). The primary outcome measure was the reduction of migraine days each month compared to a 1-month pre-diet baseline. Secondary outcome measures were 50% responder rate for migraine days, reduction of monthly migraine attacks, abortive drug intake and body mass index (BMI) change. Only data from the intention-to-treat cohort (n = 35) will be presented. Patients who dropped out (n = 6) were considered as treatment failures. Regarding the primary outcome, during the VLCKD patients experienced −3.73 (95% CI: −5.31, −2.15) migraine days respect to VLCnKD (p < 0.0001). The 50% responder rate for migraine days was 74.28% (26/35 patients) during the VLCKD period, but only 8.57% (3/35 patients) during VLCnKD. Migraine attacks decreased by −3.02 (95% CI: −4.15, −1.88) during VLCKD respect to VLCnKD (p < 0.00001). There were no differences in the change of acute anti-migraine drug consumption (p = 0.112) and BMI (p = 0.354) between the 2 diets. A VLCKD has a preventive effect in overweight episodic migraine patients that appears within 1 month, suggesting that ketogenesis may be a useful therapeutic strategy for migraines.