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Can Intermittent Fasting Help Reduce Visceral Fat?
Some dietary changes and patterns, like intermittent fasting, may be effective for shrinking visceral fat, which could protect your health.
Intermittent fasting works for some, and doctors see benefits. Is it right for you?
Alex Utter, a New Orleans bartender, began intermittent fasting six years ago, during the coronavirus pandemic.
Scientists Discover a Surprising Reason Intermittent Fasting Extends Life
How the body efficiently shifts metabolism after fasting may be key to improving health, UTSW-led research suggests.
Influencers and biohackers swear by fasting. Here’s what the science says.
Fasting can help some people reduce how many calories they eat — but it’s not “effortless” as some influencers would have you believe.
5 things patients should know about intermittent fasting
Are there health benefits to skipping meals? The "Health vs. Hype" AMA podcast explores the issue.
Intermittent fasting probably doesn’t help with weight loss
Intermittent fasting appears to be no better than doing nothing when it comes to helping people who are overweight or have obesity lose weight
Intermittent fasting no better than typical weight loss diets, study finds
Researchers say limited eating approaches such as 5:2 diet not a ‘miracle solution’ amid surge in their popularity
Intermittent Fasting Can Help You Lose Weight, But Science Says Not For the Reason You Might Think
Research shows when you eat really only matters if it means you'll eat less.
Scientists changed how zoo lions eat. Their wild side came out
Giving zoo lions whole carcasses on a feast-and-fast schedule appears to bring out more natural behavior. The lions spent nearly three times longer feeding, engaged in more tearing and manipulating of food, and rested more heavily after meals. Their activity then increased gradually during the fasting period, closely resembling the rhythm seen in wild lions.
Scientists reveal what seven days of fasting does to the human body
Scientists found that prolonged fasting triggers major changes throughout the body, but many of the most interesting effects only appeared after about three days without food. The results suggest fasting may influence health in ways that go beyond weight loss and could eventually inspire treatments that mimic its effects.
The science of Ramadan fasting
UC Riverside’s Dr. Sherif Hassan breaks down the medical benefits and potential risks of fasting.
Scientists tested intermittent fasting without eating less and found no metabolic benefit
Time-restricted eating has been widely promoted as a simple way to boost metabolic health, but new research paints a more complicated picture. When calorie intake stayed the same, an eight-hour eating window did not improve insulin sensitivity or cardiovascular markers. What did change was the body’s internal clock, which shifted based on meal timing and altered sleep patterns. The results suggest calorie reduction, not the eating window itself, may be the real driver of health benefits.
Sardine fasting: a fad or does eating only fish really boost health and weight loss?
Once a diet fad hits social media, it kind of takes on a life of its own, like sardine fasting -- eating nothing but sardines to get the body to burn fat.
A Fasting-Style Diet Seems to Result in Dynamic Changes to Human Brains
It's not just your weight that's affected.
Why a shorter eating window may not mean better metabolic health
In a nationally representative cross-sectional study of 16,973 Korean adults, researchers identified three distinct eating patterns based on the timing and distribution of daily energy intake. Eating later within a shorter daily window was associated with higher odds of metabolic syndrome, elevated blood pressure, triglycerides, and fasting glucose, while frequent grazing showed a mixed metabolic profile.
The science of Ramadan fasting
The month of Ramadan, which began last week, is when many Muslims around the world fast from dawn to sunset, refraining from food, drink, and other physical needs as an act of worship and self-discipline.
A Fasting-Style Diet Seems to Result in Dynamic Changes to Human Brains
It's not just your weight that's affected.
Study Raises Serious Questions About The Benefits of Intermittent Fasting
Calories count too.
Intermittent fasting and eating rhythmicity: what we know about their impact on metabolic and gut health
Intermittent fasting has gained attention as a strategy that may support metabolic health. Does it truly translate into measurable benefits?
Hall of Famer Joe Thomas on skipping the NFL Draft to fish, raising Wagyu and transforming his health
Cleveland Browns legend Joe Thomas reveals how intermittent fasting and cutting processed foods helped him shed weight after retiring at over 310 pounds.
The science of Ramadan fasting
UC Riverside’s Dr. Sherif Hassan breaks down the medical benefits and potential risks of fasting
Popular intermittent fasting diets may not deliver the health benefits many expect
New study suggests intermittent fasting may not deliver promised health benefits beyond weight loss, challenging beliefs about time-restricted eating.
Two simple eating habits linked to lower weight, study finds
A major study suggests that when you eat could play a key role in staying lean. People who fast longer overnight and start their day with an early breakfast were more likely to have a lower BMI years later. Scientists think this is because eating earlier aligns better with the body’s internal clock. But skipping breakfast as part of intermittent fasting didn’t offer the same advantage—and may even be tied to unhealthy habits.
What intermittent fasting really does for your body and brain
Fasting has been shown to reduce blood pressure, improve cognition, and even reverse chronic disease. But experts say the benefits may not apply to everyone.
From paleo to intermittent fasting: are any diets actually good for us?
As diet trends proliferate on social media, it can be hard to work out which are backed by science and which should be ignored. From paleo to keto, raw food to intermittent fasting, each attracts a tribe of ardent followers. Now Daniel Lieberman, professor of biological sciences at Harvard University, has written a book to try to cut through the noise. In Fed Up, he uses his background as an evolutionary anthropologist to scrutinise the evidence, turning himself into a guinea pig in the process and trying various diets. In this podcast, he tells Ian Sample which one has remained part of his routine
Scientists reveal how seven days of fasting transforms the human body
Scientists have discovered that the human body undergoes a dramatic internal transformation during extended fasting, with major changes appearing only after about three days without food. In a seven-day water-only fasting study, researchers tracked thousands of proteins in the blood and found widespread shifts affecting organs throughout the body — including the brain. While the body quickly switches from burning glucose to fat, the most intriguing biological changes linked to potential health benefits didn’t emerge until later in the fast.
Your Thymus and Your Healthspan
Our thymus gland plays a central role in the development or our immune system, specifically for supporting T cell development (how these cells got their name, maturation and differentiation in the thymus) and discriminating between self and foreign, non-self antigen proteins with production of dendritic cells. As we age, our thymus gland shrinks—the process known as involution—with progressive change from spongy to fatty tissue, with loss of functionality. But this process, with respect to timeline and extent, markedly varies from one person to the next. And to make things even more complicated, our thymus gland anatomy and precise location in the chest also is highly variable. So the famous Frank Netter diagrams from the 1960s (such as at left below) don’t capture the remarkable heterogeneity that a random set of 12 chest CT scans (below at right). What I consider as 2 landmark papers in Nature this week (here and here) used AI to quantify health of the thymus in 2 large cohorts, and then correlate the metric to a broad array of health outcomes. In this edition of Ground Truths, I’m going to cover three questions: (1) How was thymus health determined by AI?; (2) How is thymus health linked to key clinical outcomes? and (3) Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? Subscribe 1. How was thymus health determined by AI? This was accomplished by extensive work developing and validating an AI pipeline for 2 stages, the first for localization and segmentation of the thymus bed, and the second to quantify a digital marker, termed the thymic health score. There’s a lot to this algorithmic development, so I won’t go into all the details, but just provide a rudimentary outline of what was done. The 1st stage used supervised learning with 2 radiologists reviewing 2,461 chest CT scans. That work trained a 3D U-Net model to automatically identify the thymic bed’s 3D cropped region using center of mass coordinates, which reached 99.8% accuracy. The 2nd stage used a foundation model that was pre-trained with SwAV (which stands for Swapping Assignment between multiple Views), a self-supervised model, that generated a high-dimensional thymus representation of 4,096 features. That compares to the radiology reductionist and subjective scoring of 0 to 3 where 0 means the thymus is fully degenerated and fatty, and 3 is considered dense, intact glandular soft tissue. Notably, the self-supervised learning (SSL) performance was superior to supervised (AUC ~0.75 vs 0.55, respectively) reflecting the shallowness of the 0-3 classifier vs SSL’s holistic, self-taught AI. The thymic health score ranged from 0 to 100, with the highest number indexed to fully preserved thymic health. The algorithmic work extended to explainability with both Shapely value distribution, meaning the model was holistic not relying on any “magic” pixel, and occlusion sensitivity, demonstrating the model’s performance was not affected by ribs, sternum, lung tissue, but rather focused on the thymic bed directly. Below are a few saliency maps from the occlusion sensitivity that indicate the thymic bed focus, not affected by neighboring structures, using the jet color scale. Now the AI was ready for processing ~25,000 CT scans, each over 30 MB files, from the 2 large participant cohorts to provide a thymic health score, it did so in less than 14 hours, which is less than 2 seconds per scan! Share 2. How is thymus health linked to key clinical outcomes? The two cohorts were the National Lung Screening Trial, NLST (N=25,031) and the Framingham Heart Study, FHS (N=2,581) each with baseline demographics and long term follow up of >12 years for health outcomes. From the NSLT, you can see below that increased age and body-mass index were correlated to reduced thymic health. And, overall, men had reduced thymic health scores compared with women. There are a lot of graphs in the paper for outcomes, for both the NLST and FHS cohorts. To simplify the major outcomes, below is a composite Figure with striking reduction of all-cause mortality and for the different causes of death. The results were consistent between the 2 cohorts. For example, the cardiovascular mortality hazard ratio average was 0.57 in NLST and 0.38 in FHS (weighted to be 0.53 for the aggregate). The reduction of mortality also extended to digestive diseases and pulmonary disease (data not shown below). Lung cancer incidence was reduced by 36% for high vs low thymic health (Figure below, with a panel -incidence and b panel-mortality, adjusted for age, sex, BMI, smoking status). Notably, there was a smoker’s paradox: lower incidence and improved survival for lung cancer in smokers who had a high thymus health score. Smoking was associated with lower thymic scores whereas alcohol was not. Higher thymic health was linked to higher HDL cholesterol, lower triglycerides, lower fasting blood glucose, and lower systolic and diastolic blood pressure. Inflammation biomarkers, such as C-reactive protein and interleukin-6, were elevated in the people with lower thymic health scores. In their second paper, the same team looked at the relationship between thymic score and outcomes for 3,476 patients receiving cancer immunotherapy. The non-small cell lung cancer progression-free survival was reduced in patients with low thymic health score. A parallel relationship for survival was seen for other types of cancer including melanoma, breast, and kidney with a 44% lower risk among high thymic scores (Figure). A similar pattern was seen with different immune checkpoint inhibitors. The thymus health score outperformed programmed death ligand-1 (PD-L1)and tumor mutation burden (TMB) assay of the tumor and was an independent prognostic marker of progression-free survival. In this dataset, a direct connect with thymus score and adaptive immune function was noted with a correlation before cancer treatment for both T-cell diversity and thymus T-cell production (a metric known as T cell receptor excision circles). Thymus Removal Study There is a highly relevant citation about thymus function before moving onto ways to rejuvenate it. In 2023, a very important study of thymus removal during cardiothoracic surgery was published, with 1146 patients undergoing thymus removal vs 1146 matched controls (mean age 55 years). The adverse outcomes for thymus removal were striking, with a 2.9 higher risk of all-cause mortality and doubling of cancer incidence, 1.5 fold increase in cancer mortality, and 1.5-fold increase in autoimmune diseases. The immune function showed marked compromise after thymus removal, as reflected by CD4+ and CD8+ T cells (Figure below) Share Ground Truths 3. Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? In recent months we’ve learned a lot about the process of thymus involution and the pathways by which this may be modulated. Thymus involution is primarily due to loss to thymus epithelial cells (TECs) and there are 2 subtypes with different functions: the cortical, responsible for positive selection of T cells, and the medullary, for negative selection. When adipose tissue infiltrates the thymus, thymic adipocytes are pro-inflammatory, knocking out T-cell output. Likewise, systemic inflammation, or “inflammaging,” from smoking, obesity, and chronic stress promote thymic adipocytes. Now, from preclinical studies, we know about key pathways that account for these processes. Historically, back in 2014, FOXN1 was recognized as a single master transcription factor essential for TEC function, with studies in mice with forced FOXN1 upregulation leading to thymus regeneration. That laid the foundation for potential regrowth of quiescent thymus cells. It took awhile to find pathways to accomplish this goal and to even refute its role as the master regulator. The Liver-Thymus Axis Feng Zhang and his team recently showed that injection of an mRNA vaccine to the liver encoding DLL1, IL-7 and FLT3-L in combination, factors known to support thymopoiesis (Figure), successfully enhanced immune function in aged mice. However, the effect was transient. The FGF21 Story Two reports in 2025 addressed the thymus gland’s production of FGF21, a growth factor (fibroblast growth factor 21) and its control of thymus involution. This growth factor is also produced by the liver, but it doesn’t have impact on the thymus in aged rodent models. In contrast, The liver’s hepatocyte growth factor (HGF) has been shown to reverse senescent TEC structural changes. Growth hormone stimulates production of insulin growth factor-1 (IGF-1) in the liver and the thymus. Two small studies in human participants (TRIIM, for Thymus Regeneration, Immunorestoration, and Insulin Mitigation) of 6 and 50 people, respectively, treated with combined human growth hormone, metformin and DHEA, suggested the potential of slowing epigenetic aging and improving thymus mass and function. But the combination of drugs, small sample, and lack of controls make conclusions murky. Increased thymus FGF21 led to increased CD8 T cells in old mice and extended healthspan and improved physical performance. Building on the previous FOXN1 data, ablation of β-klotho, the obligatory co-receptor for FOXN1, accelerated thymic aging. The benefit to FGF21 was confirmed in a companion paper using an FGF21 knock-in mouse model showing thymus enlargement and increased TECs throughout the lifespan. (schematic Figure below). The accompanying editorial for these 2 papers speculated: “The proposed link between age-associated thymus involution and organismal aging is intriguing, and suggests we might seek to achieve systemic rejuvenation by counteracting thymic involution.” Other Factors Lessons from the Axolotl (Mexican Salamander) In an elegant set of experiments of the axolotl (Figure), known for its complete thymus regeneration after total surgical removal, mediators were identified. Surprisingly FOXN1 was dispensable. But midkine, a growth factor, appeared to be the driver, the initiator of thymus cell growth, survival, and repair. Other components that contributed were Postn+ (periostin-expressing mesenchymal niches) and Ccl19, a chemokine protein from the bloodstream. RANK and RANKL RANK (receptor activator of nuclear factor κB its ligand (RANKL) have been considered key regulators of medullary TECs. In a study of both aged mice and human thymus cell cultures, their key role was confirmed, with multiple benefits of resorting TEC function, recruitment of progenitor cells, and T cell development. Subscribe Summing Up This body of work strongly supports the health of the thymus gland as a critical regulator of human healthspan, not just a correlate or link. The new landmark studies are reinforced by the regenerative biology experimental models that have shown, via an array of mediators, that healthspan of aged mice is at least in part dependent on thymus gland function and its critical role for maintaining adaptive immunity. It sure seems that we’d be better off having an immune reservoir of naive T cells instead of a profile in older adults of exhausted, low quality, memory T cells, with a senescent phenotype. It is striking that we ignored the importance of the thymus gland for many decades. A wake-up call was the results of the thymectomy matched control study reviewed here, with the opposite of high thymic health score improved health outcomes. The convergence of AI and healthspan here is notable. The exceptional and laborious work for developing and validating (no less explaining) the AI to quantify thymus health set the foundation for probing the connect the major health outcomes in two cohorts with extensive follow-up. We’ve never had a way to meaningfully quantify the thymus gland before, so this represents important leverage of supervised, self-supervised, and transformer models. The study wouldn’t have been possible without AI. And it begs the question as to whether there are ways we can maintain our thymus at a high health score. But it’s not so simple to rejuvenate our thymus. There are multiple risks including the induction of autoimmunity, increasing the risk of cancer, and inducing a pro-inflammatory state. For example, factors that increase TEC proliferation could compromise the medulllary negative selection process and leak out auto-reactive (self-attacking) T cells. Thymic cells could be induced to proliferate, but we know, for example, that growth hormone and IGF-1 are associated with an increase risk of cancer. If thymus rejuvenation doesn’t clear out the accumulated senescent cells in older adults, then inflammation within the gland could block the production of TECs. Keeping these risks in mind, we now have identified many ways to keep our thymus healthy as we age that undoubtedly will be tested in clinical trials going forward. Ultimately, the benefit-to-risk tradeoffs will be defined. In the meantime, we have desperately needed an immunome. As I’ve stressed in multiple prior Ground Truths, we have no test in the clinic to assess a patient’s immune status! It was very encouraging for me to get an email from Hugo Aerts, the senior author of the landmark papers in the days after they were published: “I also wanted to say that your Substack on “Why We Need an Immunome” was inspiring for this work. We found it a very compelling perspective and greatly enjoyed reading it.” Just having an assessment of a person’s immune status via a chest CT scan, with millions of these performed per year, might help in guiding the right immunotherapy for cancer (e.g. more intensive, combinations for those with low thymic health scores) and help define people who are increased risk for age-related diseases of cancer, cardiovascular, and neurodegenerative. The main theme of Super Agers is that we now have many layers of data (genetics, proteins, biomarkers, organ clocks that can be integrated via multimodal AI) for us to define a person’s specific risk decades before one of these age-related diseases leads to symptoms, enabling prevention. From the new studies this week, we can add thymus health score as yet another way to understand a person’s risk, a window into their adaptive immune system and healthspan. And perhaps someday we will be able to safely rejuvenate the thymus, or maintain its health through one’s life, and use the thymus health score to monitor. NB: I wrote this post (No A.I.) A Quick Poll Loading... ********************************************************************* Thanks to Ground Truths subscribers (now > 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Share Ground Truths Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Leave a comment Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. 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