A 2024 meta-analysis (umbrella review) in the Lancet shows the nuances and value of intermittent fasting for health and well-being and gives hope to the public.

This story does not include health advice. It is for information, inspiration, and awareness purposes.

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Fasting, a practice with roots stretching back thousands of years, has only begun to be rigorously studied in clinical trials over the past six years. Despite the potential health benefits these studies might unveil, much of this crucial information remains hidden from the public eye for unknown reasons.

Instead, some authorities and the mainstream media seem to prefer amplifying unpublished manuscripts and poster presentations, panicking the public, leaving the true value of fasting studies obscured. I have touched on this disheartening reality before, where the most vital findings are kept under wraps while less substantial information takes center stage.

This story is not intended as a tirade or a claim to absolute truth but rather as a compassionate reflection inspired by the experiences of my subscribers, many of whom are esteemed scientists and clinicians. Like me, they have embraced fasting in various forms for its purported health advantages.

Fasting does not work well with glucose-dependent bodies and requires fat adaptation and insulin sensitivity. Therefore, it may not be suitable for everyone, particularly those with underlying health concerns like unmanaged diabetes, type I diabetes, children, or breastfeeding women. I respect everyone’s opinions and preferences.

However, encouraging inquiries from my readers about the scientific basis behind the health benefits of time-restricted eating has urged me to write this timely piece to update my readers and inform them of the true scientific backing behind intermittent fasting with nuances.

These discerning readers said that it is disheartening to see that much of the content circulating on social media and other platforms is anecdotal at best and sometimes outright misleading.

Recently, a cardiologist reader with an open mind exploring the health benefits of fasting for cardiovascular situations wanted to know about potential clinical studies. I am fully committed to honoring this request and shedding light on the evidence behind time-restricted eating.

Despite my three-decade journey following literature on fasting, intermittent fasting has only truly gained the spotlight in the last decade. Its rapid adoption by health and fitness communities has piqued the interest of scientists and clinicians, leading to an extensive investigation into its potential benefits, which I will summarize in this post in simple language.

With the literature evolving rapidly, I am grateful that a dedicated group of researchers took on the challenge and conducted a thorough meta-analysis, compiling all significant papers and 133 clinical trials. Their findings were published in the prestigious Lancet’s eClinical Medicine journal on March 11, 2024, providing valuable insights into the field.

They added this valuable paper to their collections in Nutrition & Metabolism, Global Health, Cardiology & Vascular Medicine, and Endocrinology which are excellent knowledge repositories for scientists, clinicians, and interested readers.

In this story, I aim to break down the key points of this remarkable study published in Lancet in March 2024. I summarize the reasons behind their research, how they conducted it, what they discovered, and what it all means to the public. Their findings shed light on important aspects of intermittent fasting, so I explain them in a way that is easy for anyone to grasp.

How did these researchers define fasting for meta-analysis?

They rigorously included the diverse categories of intermittent fasting (IF), like zero-calorie alternate-day fasting (ADF), modified alternate-day fasting (MADF), and long-term fasting as documented in the growing literature.

ADF means fasting completely one day and eating normally the next. MADF involves alternating fasting days with days of reduced calorie intake.

They also included twice-per-week fasting (TWF), where people fast for two days a week and eat normally the rest of the time. Time-restricted eating (TRE) is when someone fasts for 12–24 hours each day.

In addition, they covered periodic fasting, where people fast for longer periods less often, like a 2–5 day water fast or a 4–7 day fasting simulated diet meant to copy the effects of fasting.

I personally tried all of them in the last 30 years, even up to 10 days of fasting, putting me into deep ketosis, like giving my bloodstream 7.3 mmol/L β-Hydroxybutyrate.

Why did they do this comprehensive research?

In recent years, many clinical trials have explored the potential health benefits of intermittent fasting (IF), particularly for conditions like obesity, diabetes, cancer, and cardiovascular diseases.

These trials have shown that IF can lead to weight reduction and improvements in cardiometabolic parameters. However, there have been conflicting results in the literature regarding the changes in health outcomes following IF intervention compared to control groups.

In a 2021 umbrella review (UR) that included 11 meta-analyses comprising 130 randomized controlled trials (RCTs), researchers found that modified alternate-day fasting (MADF) for 1–2 months was associated with a reduction in body mass index (BMI) in healthy adults and those with overweight, obesity, or nonalcoholic fatty liver disease compared to a regular diet.

They selected 23 high-quality clinical trials with health outcomes.

Firstly, the UR screening process only considered obesity-related outcomes, overlooking relevant outcomes such as heart rate, total calorie intake, percentage change in body weight, and body fat. Additionally, there were discrepancies in the UR's citation accuracy, as only 10 out of the 11 systematic reviews identified were cited.

Moreover, several high-quality meta-analyses published after the retrieval deadline of the UR provided updated evidence. For example, a comprehensive review by Gu et al. (2022) found no significant results on fasting glucose after IF intervention compared to non-intervention diets, contradicting the findings of the UR.

Furthermore, a significant proportion of the studies included in the UR did not provide mean or standard deviation data, which could introduce bias in effect size estimation or hinder the interpretation and applicability of findings.

Interestingly, they mentioned that a meta-analysis conducted by Zhang et al. in 2022 yielded inconsistent results. It showed notable alterations in body weight observed after IF compared to continuous energy restriction (CER), but the difference in BMI between the two interventions did not reach statistical significance.

Overall, there has been a surge in high-quality studies investigating the health-related outcomes of IF in recent years, providing valuable insights into its efficacy and potential limitations. Therefore, they decided to systematically analyze all studies and provide valuable insights for scientists, clinicians, health authorities, and the public.

What type of methodology did they use, and how did they maintain the quality to pass peer reviews?

Their methods section outlines a rigorous approach to conducting an umbrella review (UR) to comprehensively evaluate the relationship between intermittent fasting (IF) and various health outcomes. I summarize it in my own words to make it clear.

Employing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, the researchers registered the study protocol with PROSPERO to ensure transparency and methodological rigor. They followed a meticulous search strategy across multiple databases like PubMed, Embase, Web of Science, and Cochrane, with eligibility criteria established based on Population, Intervention, Comparator, Outcome, and Study design (PICOS) criteria.

They included systematic reviews and meta-analyses of randomized controlled trials (RCTs), while observational and animal studies were excluded. They conducted quality assessment using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) and performed data synthesis, which involved categorizing effect sizes and assessing heterogeneity.

Additionally, they conducted sensitivity analyses and subgroup analyses to explore the effects of IF across different populations and health outcomes. Finally, they evaluated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria to inform evidence-based clinical decision-making regarding IF interventions.

What did they find out from so many studies?

In the “Summary effect size” section, they outlined statistically significant associations between intermittent fasting (IF) and various health outcomes, with notable effects on anthropometric measures, lipid profiles, and glycemic profiles. About 29% of associations were statistically significant, with low heterogeneity observed in 58% of cases.

In “Anthropometric measures outcomes,” they found that IF interventions led to significant reductions in fat mass and waist circumference in participants with overweight or obesity.

They observed that IF was effective in increasing fat-free mass compared to non-intervention diets. However, comparisons with continuous energy restriction (CER) did not yield significant effects on weight and BMI.

Regarding “Lipid profile outcomes,” they observed that IF interventions were associated with significant reductions in LDL-C and triglycerides (TG) and an increase in HDL-C (good cholesterol). However, they noted that some comparisons with CER did not show significant effects on total cholesterol (TC), which is useless nowadays.

In “Glycemic profile outcomes,” researchers found mixed effects of IF interventions on fasting glucose and insulin levels compared to non-intervention diets or CER. While some associations showed reductions in fasting insulin, others did not reach statistical significance.

In the “Circulatory system index” section, they highlighted the impact of IF on blood pressure, noting that one association showed less effectiveness in reducing systolic blood pressure compared to CER. They found that effects on diastolic blood pressure and heart rate were not significant in some comparisons.

In the “Appetite” section, researchers noted that none of the results provided moderate or high-quality evidence regarding the effect of IF on appetite outcomes compared to CER. Most associations did not show significant differences in hunger levels after IF intervention.

Lastly, in the “Others” section, they found that IF did not significantly affect liver stiffness or prospective food consumption compared to non-intervention diets or CER. However, some associations showed moderate evidence regarding the effects of IF on blood AST, ALT, and testosterone levels.

They observed that the quality of the evidence varied across different health outcomes, with some associations supported by high—or moderate-quality evidence. They conducted sensitivity analyses and subgroup analyses to provide further insights into the effects of IF across different populations and study characteristics.

After completing the full analysis they reported that Intermittent fasting (IF) shows promise in managing body composition, notably by reducing waist circumference and fat mass while increasing fat-free mass.

It also has positive effects on lipid profiles, including lowering LDL-C, TC, and TG levels, and increasing HDL-C levels, indicating improved cardiovascular health markers. Additionally, IF appears to enhance insulin sensitivity, as evidenced by reductions in fasting insulin levels, which could benefit individuals with type 2 diabetes or those at risk.

Overall, the findings suggest that IF may offer several health benefits for adults with overweight or obesity, particularly in terms of improving body composition, lipid profiles, and glycemic control.

Nevertheless, its effectiveness in reducing blood pressure may be less pronounced than that of other dietary interventions, like the ketogenic diet clinical studies, which I documented in two stories. They said further research is needed to fully understand the long-term effects of IF and its suitability for different populations.

How did researchers interpret the results after completion?

After wrapping up their analysis, researchers found evidence supporting intermittent fasting (IF) as helpful for improving health in many ways.

They saw that IF could reduce waist size, body fat, bad cholesterol, and triglycerides while increasing good cholesterol and muscle mass. These findings matched those of other studies, but there were some differences, likely because the studies had different sizes and durations.

The research showed that IF could significantly reduce body fat compared to regular diets, which was similar to what other studies found. However, some studies disagreed on this point, possibly because of differences in size and duration. More research with bigger groups and longer studies is needed to be sure.

Some studies found that IF lowered blood pressure compared to regular diets, while others didn’t see a big difference or even found it less helpful than other diets. Scientists need to look closer at how IF might affect sodium levels, body repair processes, gut bacteria, and inflammation to figure out why these differences happen.

The review found strong evidence that IF can improve insulin levels, likely because it helps the body use insulin better, consumes fewer calories, cleans up cells, and reduces stress.

They found that IF might be better at lowering blood sugar levels for people with obesity, maybe because it improves how insulin works and reduces inflammation. However, more research is needed to confirm this and understand how it works.

To sum up, the study highlights IF’s potential to improve health for people with overweight or obesity compared to regular diets. However, researchers still point out that more research is needed to understand how IF works and how best to use it for different health problems for different populations.

How about the limitations of the study?

Despite shedding light on the effects of various fasting on diverse health issues, including mental health, the study had limitations like differences between studies, small groups, and excluding some types of studies that did not fit their criteria. Those exclusions might affect how well the findings apply to a broader population. Plus, the review didn’t look at the potential side effects of fasting, so more research is needed to understand the adverse effects of IF. I documented side effects, known as keto flu, which are manageable based on my experience.

Why have I been fasting for over 30 years?

For 30 years, I have been drawn to its potential benefits for health and well-being. As I have examined the science behind fasting, questions have arisen regarding its effects on various health conditions I faced, like prediabetes, abdominal obesity, arthritis symptoms, leaky gut, and brain fog, prompting me to explore the benefits of fasting further.

Firstly, fasting enhances insulin sensitivity, a key factor in managing conditions like metabolic syndrome, prediabetes, type II diabetes, heart disease, some cancers, and neurodegenerative diseases like dementia.

Evidence in a Nature paper suggests fasting’s role in enhancing insulin sensitivity and reducing oxidative stress and inflammation, key factors in combating these conditions. Studies propose that fasting restricts glucose and glutamine, limiting fuel for cancer cells and potentially controlling their growth.

Secondly, fasting has been shown to trigger self-healing processes like autophagy and mitophagy, which can promote healing in arteries and reduce inflammation, typically beneficial for heart, immune, and neurological health.

Thirdly, fasting can lower blood sugar and blood pressure, traditionally viewed as markers of heart health. Moreover, fasting provides an alternative energy source to the heart and brain in the form of ketone bodies, which can reduce oxidative stress and inflammation, typically harmful to heart and neurological health.

Lastly, fasting’s role in improving mitochondrial health through processes like mitophagy and mitochondrial coupling offers promising benefits for energy, healthspan, and lifespan.

Studies highlight fasting’s influence on circadian rhythm genes in adipose and skin tissues. Additionally, fasting activates counter-regulatory responses involving the autonomic nervous system and epinephrine release, vital for maintaining blood glucose levels.

Animal studies suggest fasting’s role in longevity by activating pathways like sirtuins and AMPK while temporarily inhibiting mTOR, key mechanisms that regulate cellular energy and potentially extend lifespan.

In essence, my journey with fasting has led me to confront these complex issues, challenging conventional understandings and prompting a deeper exploration of the relationship between fasting, cardiometabolic processes, neurological health, and cognitive performance.

I recently touched on the benefits of fasting and meditation for enhancing memory in a story titled A New Neuroscience Study Reveals the Secret of Super-Agers’ Remarkable Memories. I will share this new story on NewsBreak soon.

Ketosis, particularly β-Hydroxybutyrate, contributes to neuroprotection and neuroplasticity, potentially guarding against neurodegenerative diseases and enhancing cognitive abilities. This metabolic shift to ketones as brain fuel may offer protection and support cognitive clarity.

The key mechanisms of fasting are ketogenesis and β-Hydroxybutyrate, which I explained in two separate stories in different contexts before. I explained the mysteries of ketogenesis and gluconeogenesis based on deep research and my decades of experimentation. I also covered the impact of fasting on hippocampal neurogenesis.

A paper in Nature indicates fasting’s role in improving long-term memory and brain function by promoting BDNF production. I documented a summary of my research in an article titled Here’s How Fasting Can Change Brain Chemistry.

Ketogenesis can increase mitochondrial bioenergetics activation and neurotrophic factors (BDNF and NGF), resulting in the proliferation of neural progenitor and neural stem cells. Neurotrophin proteins help neurons form new connections and strengthen existing ones, which is essential for cognitive and neuronal functions in the brain.

Thank you for reading my perspectives. I wish you a healthy and happy life.

If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.