Iron homeostasis in older adults: balancing nutritional requirements and health risks.

Iron plays a crucial role in many physiological processes, including oxygen transport, bioenergetics, and immune function. Iron is assimilated from food and also recycled from senescent red blood cells. Iron exists in two dietary forms: heme (animal based) and non-heme (mostly plant based). The body uses iron for metabolic purposes, and stores the excess mainly in splenic and hepatic macrophages. Physiologically, iron excretion in humans is inefficient and not highly regulated, so regulation of intestinal absorption maintains iron homeostasis. Iron losses occur at a steady rate via turnover of the intestinal epithelium, blood loss, and exfoliation of dead skin cells, but overall iron homeostasis is tightly controlled at cellular and systemic levels. Aging can have a profound impact on iron homeostasis and induce a dyshomeostasis where iron deficiency or overload (sometimes both simultaneously) can occur, potentially leading to several disorders and pathologies. To maintain physiologically balanced iron levels, reduce risk of disease, and promote healthy aging, it is advisable for older adults to follow recommended daily intake guidelines and periodically assess iron levels. Clinicians can evaluate body iron status using different techniques but selecting an assessment method primarily depends on the condition being examined. This review provides a comprehensive overview of the forms, sources, and metabolism of dietary iron, associated disorders of iron dyshomeostasis, assessment of iron levels in older adults, and nutritional guidelines and strategies to maintain iron balance in older adults.

Does time-restricted eating add benefits to calorie restriction? A systematic review.

OBJECTIVE: A growing body of evidence has supported the health benefits of extended daily fasting, known as time-restricted eating (TRE); however, whether the addition of TRE enhances the known benefits of calorie restriction (CR) remains unclear. METHODS: PubMed, Scopus, the Cochrane Library, and Google Scholar were searched through April 2023. This systematic review includes randomized controlled trials (RCTs) that compared CR + TRE with CR alone in energy-matched conditions of at least 8 weeks in duration that assessed changes in body weight and cardiometabolic disease risk factors in adults with overweight and/or obesity. RESULTS: Seven studies were identified (n = 579). Two studies reported greater weight loss and reductions in diastolic blood pressure with CR + TRE compared with CR alone after 8 to 14 weeks, whereas one study reported greater improvements in triglycerides and glucose tolerance with CR + TRE (3 days/week) compared with CR alone following 26 weeks. One study reported significant increases in homeostatic model assessment of insulin resistance (HOMA-IR) levels with CR + TRE versus CR alone after 8 weeks. There were no statistically significant differences in any other outcome variable between the two interventions. CONCLUSIONS: The addition of TRE to CR regimens resulted in greater weight loss and improvements in cardiometabolic risk factors in some studies; however, the majority of studies did not find additional benefits.

Use of Minimally Invasive Methods to Assess Fuel Utilization and Circadian Rhythms in Older Adults.

Aging is associated with multiple physiological changes that contribute synergistically and independently to physical disability and the risk of chronic disease. Although the etiology of age-related physical disability is complex and multifactorial, the decline in mitochondrial function appears to coincide with the progression of functional decline in many older adults. The reason why there is a decrease in mitochondrial function with aging remains elusive, but emerging science indicates that both fuel metabolism and circadian rhythms can influence mitochondrial function. Recent studies have established that circadian rhythms become disturbed with aging, and that disrupted circadian rhythms have pathological consequences that impact mitochondrial function and overlap with many age-associated chronic diseases. Current quantitative methods for direct assessment of mitochondrial function are invasive and typically require a muscle biopsy, which can pose difficulties with participant recruitment and study adherence, given the perceived levels of potential pain and risk. Thus, an innovative and relatively noninvasive protocol to assess changes in mitochondrial function at the cellular level and circadian patterns in older adults was adapted. Specifically, a real-time metabolic flux analyzer is used to assess the mitochondrial bioenergetic function of white blood cells under differential substrate availability. The expression of circadian clock genes in white blood cells to cross-correlate with the mitochondrial bioenergetics and circadian rhythm outcomes are also analyzed. It is believed that these innovative methodological approaches will aid future clinical trials by providing minimally invasive methods for studying mitochondrial substrate preference and circadian rhythms in older adults.

The Effects of Isocaloric Intermittent Fasting vs Daily Caloric Restriction on Weight Loss and Metabolic Risk Factors for Noncommunicable Chronic Diseases: A Systematic Review of Randomized Controlled or Comparative Trials.

BACKGROUND: Intermittent fasting (IF) has gained favor as an alternative regimen to daily caloric restriction (DCR). Therefore, there is a need for systematic reviews of randomized controlled/comparison trials examining the effects of isocaloric IF vs DCR on metabolic risk factors for noncommunicable chronic diseases. OBJECTIVE: To systematically investigate the effects of isocaloric IF vs DCR on metabolic risk factors for noncommunicable chronic diseases in adults with overweight and obesity. METHODS: Five online databases (PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar) were searched for articles published from January 2000 through April 2022. The updated Cochrane Risk of Bias Assessment tool for randomized controlled/comparison trials was used to assess risk of bias in the included studies. This review includes randomized controlled/comparison trials with matched energy intakes (isocaloric) between IF and DCR among adults with overweight and obesity with ≥8-week durations, that assessed risk factors related to obesity and for diabetes, cardiovascular diseases, and cancers. RESULTS: Thirteen randomized controlled/comparison trials with matched energy intakes (isocaloric) between IF and DCR were identified. The effects of IF on weight loss and metabolic risk markers of diabetes, cardiovascular diseases, and cancers were varied but generally comparable with DCR. IF (4:3 and 5:2 diets) was superior to DCR for improving insulin sensitivity in two studies. Reductions in body fat were significantly greater with IF (5:2 diet and time-restricted eating) than DCR in two studies of isocaloric diets. CONCLUSIONS: With matched energy intakes, IF interventions produced similar beneficial effects for weight loss and chronic disease risk factors compared with DCR. Very limited evidence suggests that IF may be more effective vs DCR for fat loss and insulin sensitivity, but conclusions cannot be drawn based on the current evidence. Future clinical studies with larger populations and longer durations are needed for further elucidation of any potential effects of IF regimens for prevention of noncommunicable chronic diseases.

The effects of time-restricted eating on sleep, cognitive decline, and Alzheimer's disease.

According to the United Nations, by 2050, one in six individuals will be over age 65 globally, and one in four people would be aged 65 and older in western countries. The unprecedented growth of the aging population is associated with increased age-related disorders like Alzheimer's disease (AD) and Mild cognitive impairment (MCI). To date, no cure is known for AD, thus lifestyle interventions including calorie restriction (CR) and time-restricted eating (TRE) are proposed as potential approach to delay the onset and progression of the disease. Sleep disturbances are common in people with MCI and AD. Moreover, accumulating data indicates that pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8 and IL-10 increase in individuals with AD and MCI versus healthy subjects. Thus, the purpose of the present review is to describe the potential effects of TRE on sleep, cognition decline, and neuroinflammatory markers in humans. Preliminary evidence suggests that TRE may produce neuroprotective effects on cognition and reduce neuroinflammatory markers related to AD in humans. To date, no studies investigated the effects of TRE on sleep disturbances and patients with AD. Thereby, the impact of TRE on cognition in individuals with cognitive decline and AD needs to be investigated further in randomized controlled trials (RCTs).

Importance of Intermittent Fasting Regimens and Selection of Adequate Therapy on Inflammation and Oxidative Stress in SARS-CoV-2 Infection.

The unpredictable nature of new variants of coronavirus 2 (SARS-CoV-2)-highly transmissible and some with vaccine-resistance, have led to an increased need for feasible lifestyle modifications as complementary therapies. Systemic inflammation is the common hallmark of communicable diseases like severe coronavirus disease 2019 (COVID-19) and non-communicable chronic diseases (NCDs) such as obesity, cardiovascular diseases (CVD), diabetes mellitus, and cancers, all for which mitigation of severe outcomes is of paramount importance. Dietary quality is associated with NCDs, and intermittent fasting (IF) has been suggested as an effective approach for treatment and prevention of some NCDs, similar to that of caloric restriction. There is a paucity of high-quality data from randomized controlled trials regarding the impact of IF and the intake of specific nutrients on inflammation and post-infection outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current review of recent literature was performed to explore the immunomodulatory roles of IF regimens and supplements involving the intake of specific nutrients including vitamins (A, B, C, D, and E), zinc, and nutraceuticals (n-3 polyunsaturated fatty acids, quercetin, and probiotics) on inflammatory and oxidative stress markers, with consideration of how they may be related to SARS-CoV-2.

The effects of intermittent fasting regimens in middle-age and older adults: Current state of evidence.

Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence and an increased risk of mortality. The unprecedented growth of the aging population has thus created an urgent need for interventions that can preserve older adults' capacity to live independently and to function well. To date, there is no conclusive evidence supporting the efficacy of an intervention to prevent or reverse physical disability in older persons at risk of functional decline. A growing body of evidence indicates that prolonged fasting periods and different types of intermittent fasting regimens can have positive effects on anthropometric and metabolic health parameters in middle-aged adults similar to that of calorie restriction. For this reason, there is increasing scientific interest in further exploring the biological and metabolic effects of intermittent fasting approaches, as well as the feasibility and safety of popular types of intermittent fasting regimens in older adults. Thus, the purpose of the present review is to describe the state of evidence of different types of intermittent fasting regimes, specifically time-restricted eating and 5:2 intermittent fasting, in the growing population of middle-aged and older adults. A small, but growing body of evidence indicates both time restricted eating (TRE) and 5:2 intermittent fasting approaches can produce modest weight loss; however, only the 5:2 approach produced clinically meaningful weight losses. Reductions in blood pressure were observed for both TRE and 5:2 fasting approaches, but the effects were not consistent across studies. The majority of studies to date, in middle-age and older adults, however, have been of short duration in small study samples. Future clinical trials with larger populations and longer intervention durations are required to better understand the risks versus benefits of different types of intermittent fasting regimens in middle-age and older individuals.