Reviewing the Effects of Intermittent Fasting on Cognitive Function in Later Life
A reduced calorie intake produces beneficial changes to metabolism, promoting autophagy and cell maintenance, among other mechanisms, improving health and leading to a modestly slowed pace of aging. Interestingly, adjusting the time of eating in order to experience longer periods of hunger while still consuming the same calorie intake produces outcomes that are broadly similar at the high level, even if somewhat different at the detailed level of metabolism and cell biochemistry.
One might look at the great breadth of research into calorie restriction, time-restricted feeding, and intermittent fasting and conclude that one of the more important factors in the results achieved is the amount of time spent in a state of hunger. In other words that it is the hunger-associated signaling and cellular reactions to that signaling that provide a sizable fraction of the benefits observed when calories are consistently reduced. There are, must be, other mechanisms at work, of course. A low calorie diet sustained over time reduces the burden of harmful inflammatory visceral fat tissue, for example. Further, reducing specific dietary components such as methionine without reducing overall calorie intake can trigger nutrient sensors to induce some of the benefits of calorie restriction. It is an interesting area of study.
Nutrition is one of the modifiable lifestyle factors that has been identified as a potential target for interventions in older adults' cognitive health and mental well-being. Time Restricted Eating (TRE) and Intermittent Fasting (IFA) are two dietary approaches that have gained popularity in recent years due to their potential health benefits. Time Restricted Eating (TRE), an approach rooted in the alignment of eating patterns with circadian rhythms, centers on limiting the span of time during which food consumption occurs each day and emphasizes the importance of when we eat, along with underscoring the intricate interplay between nutrition and the body's internal clock within a disciplined time frame typically ranging from 8 to 12 hours.
On the other hand, IFA encompasses a spectrum of fasting regimens with the common thread of cycling between periods of food consumption and periods of calorie restriction or fasting. These dietary approaches, TRE and IFA, have demonstrated their efficacy in improving metabolic health by enhancing factors such as insulin sensitivity, glucose metabolism, and lipid profiles. Additionally, these approaches have been associated with factors linked to increased longevity, including improvements in cardiovascular health and a reduction in the risk of age-related diseases.
Studies have suggested that both IFA and TRE may have beneficial effects on cognitive function and mental health in older adults. The mechanisms underlying these effects are complex and multifaceted, but may involve improvements in glucose metabolism, inflammation, oxidative stress, and neuroplasticity. Both IFA and TRE involve periods of fasting, which can lead to a decrease in insulin resistance and an increase in insulin sensitivity. This can, in turn, improve glucose uptake in the brain, which is important for preserving cognitive function and minimizing the risk of cognitive decline. Additionally, improved glucose metabolism may have a protective effect on the brain, lowering the likelihood of neurodegenerative conditions like Alzheimer's and Parkinson's. IFA and TRE may also modulate the gut microbiome, which has been implicated in brain function and mental health.
Recent studies have delved into the association between TRE, cognitive function, and mental health in older adults, yielding somewhat mixed results. While our findings suggest a relationship between TRE and IFA practices and cognitive function and mental health among older adults, it is important to acknowledge the complexity of this relationship. Various factors, including the duration and timing of the eating window and the physical condition of older adults, or even specific subgroups like those aged 70 years and older, can influence the outcomes.
Our systematic review encompasses a range of study designs, each offering unique insights into the effects of fasting interventions on cognitive function and mental health in older adults. Cross-sectional studies revealed that individuals practicing TRE were less likely to exhibit signs of mental health distress, particularly those aged over 70 years. Experimental designs provided preliminary evidence regarding the feasibility and potential efficacy of fasting interventions. Cohort studies tracked participants over time and found that individuals regularly practicing IFA were more likely to revert to successful aging with no cognitive impairment compared to those with irregular or no IFA practice.
I'm not advocating that this specific paper is the end-all point of knowledge about intermittent fasting, but what are your thoughts on the potential health detriments that might be caused by eating a ton of calories in a short period of time (as you are likely to do if you are following a time-restricted eating pattern)?
"Abstract
Introduction: Time-restricted eating (TRE) has gained popularity as a dietary intervention that limits daily food consumption to a 4- to 12-hour window. Most short-term randomized controlled trials reported that TRE improved cardiometabolic risk profiles. However, whether TRE is associated with long-term hard endpoints remains unknown.
Hypothesis: We assessed the hypothesis that TRE is associated with a reduced risk of all-cause and cause-specific mortality.
Methods: Participants aged at least 20 years who completed two valid 24-hour dietary recalls and reported usual intake in both recalls were included from the National Health and Nutrition Examination Survey in 2003-2018. Mortality status as of December 2019 was obtained through linkage to the National Death Index. An eating occasion required consuming more than 5 kcal of foods or beverages. Eating duration between the last and first eating occasion was calculated for each day. The average duration of two recall days defined typical eating duration which was then categorized as <8, 8-<10, 10-16 hours. Multivariable Cox proportional hazards models were employed to estimate the association of eating duration with all-cause and cause-specific mortality in the overall sample and among adults with cardiovascular disease or cancer. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were derived.
Results: Among 20,078 adults included, the weighted mean (SE) age was 48.5 (0.3) years, 50.0% were men, and 73.3% were non-Hispanic White. During a median follow-up of 8.0 years (IQR, 4.2-11.8), 2797 all-cause deaths occurred, including 840 cardiovascular deaths and 643 cancer deaths. Compared with eating duration of 12-16 hours, eating duration <8 hours was significantly associated with an increased risk of cardiovascular mortality (HR, 1.96 [95% CI, 1.23-3.13]); this association was also observed in adults with cardiovascular disease (HR, 2.06 [95% CI, 1.12-3.81]) and adults with cancer (HR, 2.72 [95% CI, 1.28-5.80]). Other eating durations were not associated with cardiovascular mortality, except for eating duration of 8-16 hours was associated with a lower risk of cancer mortality in people with cancer (HR, 0.46; [95% CI, 0.22-0.95]).
Conclusions: In US adults, TRE with eating duration <8 hours was significantly associated with a higher risk of cardiovascular mortality in the general population as well as in people with cardiovascular disease or cancer. These findings do not support long-term use of 16:8 TRE for preventing cardiovascular death."
https://www.heart.org/en/news/2024/03/18/time-restricted-eating-may-raise-cardiovascular-death-risk-in-the-long-term
They do in fact take into account weight loss in the NEJM publicaton.
They looked at estimated glomerular filtration rate (eGFR), a key measure of kidney function, calculated in two ways - based on creatinine and based on cystatin C.
Weight loss can "artificially" lower creatinine and inflate eGFR. However, they found the kidney benefits were consistent regardless of the eGFR calculation method, and the cystatin C method is not impacted by weight loss.
Additionally, they directly compared creatinine-based and cystatin C-based eGFR changes at week 104 and found them to be nearly identical between semaglutide and placebo groups. This provides strong evidence the kidney benefits were independent of the weight loss effects of semaglutide.
"In addition, the effect of semaglutide was unrelated to changes in body weight regardless of whether the eGFR was computed with serum creatinine, cystatin C, or both, and consistent effects on creatinine-based and cystatin C-based eGFR were identified in this trial."
As someone who is otherwise lean, healthy, and good lifestyle habits (diet, exercise, sleep, etc.), and yet struggles with age-related kidney disfunction, hard to see this as "hype" rather than quantifiably hopeful.
https://gwern.net/doc/longevity/glp/semaglutide/2024-perkovic.pdf