2.1.3. Intermittent Fasting
There are several approaches of intermittent fasting. The 16:8 concept is a form oftime-restricted eating where individuals eat within a time window of 8 h and fast for the remaining 16 h daily. The 5:2 concept consists of a normal eating routine on 5 days per week, without any specific recommendations or restrictions, and 2 days of fasting with an energy intake of about 500 kcal. Conley M. et al. compared the 5:2 diet (2 non-consecutive days with 600 kcal and 5 days of energy intake ad libitum per week) with an energy-reduced diet. After 6 months of intervention, both groups reduced their body weight similarly (5.3 kg
(5:2) vs. 5.5 kg (standard)) with no significant difference [44]. A RCT compared the effects of alternate-day fasting with daily caloric restriction on body weight in participants with obesity. Findings demonstrate comparable weight loss after 6 (alternate day fasting: 6.8%, caloric restriction: 6.8%) and 12 months (6.0% versus 5.3%) [45]. In a systematic review and meta-analysis of RCTs intermittent versus continuous energy restriction on weight loss and cardio-metabolic outcomes have been investigated. The included eleven trials with a duration from 8 to 24 weeks resulted in a similar weight loss between the two intervention
groups [46]. Compared to a continuous energy restriction, intermittent fasting leads to similar weight loss and similar improvement of cardio-metabolic parameters [47–49]. The recently published Cochrane review by Allaf et al. found that people lost more weight with intermittent fasting concepts than without a special dietary concept over three months (evidence from seven studies in 224 people). If intermittent fasting concepts were compared with energy-restricted diets for 3 months (10 studies; 719 people) or longer (3 to 12 months; 4 studies; 279 people), this difference in weight loss is lost [50]. The energy restriction
causes the positive effect of intermittent fasting on weight loss, not fasting as a stand-alone intervention [51,52].Besides weight loss, fasting-specific effects on metabolic regulation or cardiovascular health are discussed. In lean persons, there is no statistically significant difference between daily energy restriction and alternate-day fasting with or without energy restriction concerning postprandial indices of cardio-metabolic health, gut hormones, or the gene
expression in subcutaneous adipose tissue [51].A small study with eleven participants with overweight, early time-restricted fasting (eating between 8 a.m. and 2 p.m.) was investigated for acute effects on glucose metabolism and gene expression. In comparison to the control group (eating between 8 a.m. to 8 p.m.)
24 h glucose levels and glycaemic excursions decreased, and ketones, cholesterol, and the expression of the stress response and aging gene sirtuin 1 (SIRT1) and the autophagy gene microtube associated protein 1 light chain 3 alpha (LC3A) increased in the morning before breakfast. This was different to the gene expression pattern in the evening [53]. The early time-restricted feeding effect on cardio-metabolic health (insulin sensitivity, betacell responsiveness, blood pressure, oxidative stress, and appetite)—independent from weight loss—has further been observed by Sutton et al. in men with prediabetes [54]. In
addition, a RCT with 17 participants with normal weight compared the metabolic effects of breakfast and dinner skipping. Compared to the three meals per day control group, Nutrients 2022, 14, 169 7 of 15 skipping breakfast or dinner increased energy expenditure. Furthermore, fat oxidation increased on the breakfast skipping day [55]. In a prospective cohort study, it has been shown that breakfast skipping is associated with a 21% increased risk for the development
of diabetes mellitus type 2 [56]. 2.1.4. Personalized Nutrition In the last years, concepts of personalized nutrition have been more focused, especially by commercial providers offering direct-to-consumer genetic testing. One of the main drivers for personalized dietary recommendations is the inter-individual variability of metabolic response on standardized meal challenges suggesting that personalized diets might successfully modify elevated postprandial blood glucose and its metabolic consequences [57]. In the Personalised Responses to Dietary Composition Trial (PREDICT1) with more than 1000 twins and unrelated healthy adults in the UK, large inter-individual variability in postprandial responses of blood triglycerides (103%), glucose (68%), and insulin (59%) following identical meals was observed. Various intrinsic and extrinsic factors could be identified as predictors of the inter-individual variability. In the following, scientific evidence of gene-based and microbiome-based dietary recommendations is summarized.
Gene-Based Dietary Recommendations
Gene-based dietary recommendations are based on individuals’ genetic make-up. The fact that body weight is, inter alia, genetically determined, and more than hundreds of genetic loci are identified for a relationship with anthropometric parameters [58], is underlining the assumption that even the inter-individual varying degree of success in weight loss indicates a genetic component [59]. The fat mass and obesity-associated (FTO) gene is the gene with the largest effect on body weight. The function of the FTO gene is not yet fully understood, whereas it is shown that the FTO gene inhibits brown adipose tissue genesis [60]. Numerous companies offer genotyping and provide recommendations for a healthy diet or weight loss. Furthermore, commercial offerings for deoxyribonucleic acid (DNA) methylation profiling started to emerge. These commercially available direct-toconsumer tests are in contrast to the lacking scientific evidence that genotypes are associated with weight loss. In a recently published pooled analysis of weight loss data, it has been shown that single nucleotide polymorphisms have a minor role in the inter-individual variation of weight loss [61]. The Food4Me study has shown that including genotype information for dietary recommendations had no beneficial effect on weight loss [62]. The American Society of Dietetics and Nutrition clearly states that ”No significant differences in weight, body mass index (BMI; calculated as kg/m2), or waist circumference were observed when results of genetic testing were incorporated into nutrition counselling compared with counselling or care that did not incorporate genetic results” [63], and the “use of nutrigenetic testing to provide dietary advice is not ready for routine dietetics practice” [64]. Present research cannot provide adequate evidence that individuals with a defined genetic make-up benefit especially from specific dietary recommendations concerning weight loss [65]. A systematic review on gene–diet interactions on weight change concluded that there is no evidence that gene–diet interactions are a main determinant for obesity treatment success [66]. For that reason, more future human studies are required to prove the clinical evidence of gene-based dietary recommendations on weight loss [59]. Furthermore, the investigation of single nucleotide polymorphisms will be replaced by the investigation of polygenetic scores to characterize humans according to their genetic predisposition. Khera AV et al. have developed and validated a genome-wide polygenetic score for five diseases (coronary heart disease, atrial fibrillation, diabetes mellitus type 2, inflammatory bowel disease, and
breast cancer) [67]. In a further data analysis, a polygenetic predictor for body weight has been developed and validated [68].
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