Autophagy slows age‐related pathologies and is stimulated by nutrient restriction in animal studies. However, this has never been shown in humans. We measured autophagy using a physiologically relevant measure of autophagic flux (flux of MAP1LC3B isoform II/LC3B‐II in peripheral blood mononuclear cells in the context of whole blood) in 121 humans with obesity who were randomised to standard care (SC, control condition), calorie restriction (CR) or intermittent fasting plus time‐restricted eating (iTRE) for 6 months. While the differences in change from baseline between groups was not significant at 2 months, we observed a significant difference in change from baseline between iTRE compared to SC at 6 months (P = 0.04, post hoc analysis). This effect may be driven partly by a tendency for autophagy to decrease in the SC group. The difference in change from baseline between CR and SC was not significant. Uncorrected analysis of correlations showed a negative relationship between change in autophagy and change in blood triglycerides. Data on the specificity and performance of the methods used to measure human autophagy are also presented. This shows autophagy may be increased by intermittent nutrient restriction in humans. If so, this is a demonstration that nutrient restriction can be used to improve a primary hallmark of biological ageing and provides a mechanism for how fasting could delay the onset of age‐related disease. image Key points: Autophagy slows biological ageing, and dysfunction of autophagy has been implicated in age‐related disease – an effective way of increasing autophagy in cells and animal models is nutrient restriction. However, the impact of different types of nutrient restriction on physiological autophagic flux in humans has not been extensively researched. Here we measure the effect of intermittent time‐restricted eating (iTRE) and calorie restriction on physiological autophagic flux in peripheral blood mononuclear cells. After 6 months, there was a significant difference in change from baseline between the iTRE and the standard care control group, with flux being higher in the iTRE group at this timepoint. However, there was no significant increase from baseline within the iTRE group, showing that although autophagy may be modified by nutrient restriction in humans, further studies are required.

Iron supplementation is commonly recommended for the prevention and treatment of maternal iron deficiency (ID) or iron deficiency anemia (IDA). However, the impacts of prophylactic of therapeutic prenatal iron supplementation on child neurodevelopment in upper middle-income (UMI) and high-income countries (HICs), where broad nutritional deficiencies are less common, are unclear. To investigate this, we conducted a systematic review, searching four databases (Medline, CINAHL, EMBASE, Cochrane Library) through 1 May 2023. Randomized controlled trials (RCTs) assessing oral or intravenous iron supplementation in pregnant women reporting on child neurodevelopment (primary outcome: age-standardized cognitive scores) were eligible. We included three RCTs (five publications) from two HICs (Spain and Australia) (N = 935 children; N = 1397 mothers). Due to clinical heterogeneity of the RCTs, meta-analyses were not appropriate; findings were narratively synthesized. In non-anemic pregnant women, prenatal iron for prevention of IDA resulted in little to no difference in cognition at 40 days post-partum (1 RCT, 503 infants; very low certainty evidence). Similarly, the effect on the intelligence quotient at four years was very uncertain (2 RCTs, 509 children, very low certainty evidence). No RCTs for treatment of ID assessed offspring cognition. The effects on secondary outcomes related to language and motor development, or other measures of cognitive function, were unclear, except for one prevention-focused RCT (302 children), which reported possible harm for children’s behavioral and emotional functioning at four years. There is no evidence from UMI countries and insufficient evidence from HICs to support or refute benefits or harms of prophylactic or therapeutic prenatal iron supplementation on child neurodevelopment.

Aim: This qualitative study aimed to explore the experiences of participants who were enrolled in 6‐month controlled weight loss interventions with 2‐month follow‐up to better understand the process of behaviour change and maintenance.Methods: Fifteen participants who completed or dropped out from either a daily energy restriction or intermittent fasting group were recruited using maximum variation purposive sampling. In‐depth, semi‐structured interviews were conducted at the 2‐month follow‐up phase. All interviews were transcribed and analysed using thematic analysis, guided by behaviour change models including transtheoretical model, social cognitive theory and integrated model of change.Results: Participants following both diets showed similar behaviour change patterns. Their first motivations were mostly external and relied on ‘accountability’ to adhere to the diet when initiating the dietary changes. Participants highlighted the importance of frequent reviews and monitoring in assisting their adherence. This feedback system promoted the development of self‐efficacy and internalised motivation to encourage an ‘ownership’. Participants who transitioned successfully from relying on accountability to take ‘ownership’ of the intervention were more capable of tackling challenges and tailoring their diet to form a new routine for long‐term maintenance.Conclusion: External motivations were key to initiate while internalised motivations were more important to sustain the behaviour change. Health professionals can assist this process through routine monitoring and feedback processes in clinical practice.