Recent Research on Fasting and Calorie Restriction (March 2024)

1/ Unveiling How Calorie Restriction Boosts Muscle Repair

An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program.

Using a transgenic mouse model, in a new study, researchers identify liver-secreted plasminogen as a key regulator of this process. Blocking circulating plasminogen or its receptor prevents the expansion of muscle stem cells during CR. This signaling mechanism also holds true in human subjects from the CALERIE trial. Essentially, CR prompts the liver to release more plasminogen, which directly signals muscle stem cells to proliferate, enhancing muscle resilience during calorie restriction.

This adds important knowledge to address misconceptions about the loss of muscle mass during fasting. Muscles are preserved by protein-sparing mechanisms, and it starts to be clear that any muscle loss could even be recovered after fasting by the activation of regeneration programs. This is also what we see in our last study on muscle function, strength was maintained in non-weight-bearing muscles and increased in weight-bearing muscles during long-term fasting, and there was a detectable muscle growth during the food reintroduction.

2/ Neuroprotective effects of caloric restriction against acute inflammatory challenges

This study explores how reducing calorie intake might protect against infection-induced inflammation. Researchers focused on the effects of a reduced-calorie diet in rats, especially when faced with an acute inflammatory challenge, such as an infection mimic by acute lipopolysaccharide (LPS) administration. LPS is a molecule found on the outer membrane of certain bacteria that can trigger strong immune responses. The diet lessened inflammation markers in the blood and brain, particularly in areas involved in inflammation and memory. The diet also improved the brain's antioxidant capacity, suggesting a mechanism by which calorie restriction could help protect the brain during inflammation and possibly slow down aspects of aging and disease progression.

3/ Proteome adaptions to 7 days of fasting in humans

Probably one of the best studies on fasting published so far this year!Researchers conducted a 7-day water-only fast with 12 volunteers (5 women, 7 men). By analyzing over 3,000 proteins (aka the proteome) in the blood before, during, and after fasting, the team uncovered nine distinct response profiles.?I have provided a few details about the significance of this study in an earlier post.

4/ ?Intermittent fasting promotes rejuvenation of immunosenescent phenotypes in aged adipose tissue

Aging in white fat tissue is marked by the decline of certain stem cells and changes in immune cells, contributing to metabolic problems. However, removing these aging cells can enhance health. This research revealed that intermittent fasting in aged mice can reduce aging signs in fat tissue stem cells and improve their function. Additionally, intermittent fasting increased a type of immune cell that helps maintain healthy fat tissue in older mice. These findings suggest intermittent fasting could be a practical way to combat the negative effects of aging on fat tissue and prevent related metabolic diseases.

5/ Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats

This study investigated the effects of combining SCD Probiotics with intermittent fasting (IF) on the intestinal health of rats during 30 days. The research showed that this combination improved the condition of the lower intestine tissues. The study particularly highlighted that the probiotics, especially when used with IF, had a pronounced positive impact on the colon. Both IF and SCD Probiotics were found to have protective effects on intestinal structure and stability by reducing mast cell density and levels of TNF-α and NF-κB expression in ileum and colon tissues, thus potentially mitigating age-related intestinal damage and inflammation. The results suggest that intermittent fasting, together with SCD Probiotics, could be effective in preventing or reducing age-related intestinal issues and inflammation, offering a synergistic protective effect.

A word of caution: Note that it might not be the case during longer periods of fasting when the intestinal tract is emptied and inactive. In addition, probiotics’ effects lack consensus; they may work for some but not all. There is still a lot to know before we can reliably recommend the use of probiotics during fasting.

6/ Comparison of three methods of intermittent fasting in high-fat-diet-induced obese mice

This study explored the effects of three popular intermittent fasting methods on obese mice fed a high-fat diet. The mice were initially fed either a normal or high-fat diet. Then, groups were subjected to different fasting protocols: Alternate Day Fasting (ADF), Time-Restricted Feeding (TRF), or the 5:2 Diet.

All of the fasting protocols can prompt acceptable energy restriction and the ADF and TRF protocols can significantly cause weight loss. Also, the TRF and 5:2 Diets can lower the visceral adiposity. To be honest I don't think this brings anything valuable which can be translated to human physiology because of the major differences between human and mice.

7/ Modulation of intestinal metabolites by calorie restriction and its association with gut microbiota in a mouse model of colorectal cancer

The study delved into how calorie restriction influences intestinal metabolites and gut microbiota in a mouse model of colorectal cancer.

Using human colorectal cancer cells, researchers created a mouse model and compared mice with normal diets to those under calorie restriction. They analyzed intestinal metabolites and examined the relationship between gut microbiota and metabolites.?

Results showed that calorie-restricted mice had lower levels of Isoleucyl-Valine but higher levels of D-Proline, 1-Palmitoylphosphatidylcholine, and 4-Trimethylammoniobutanoic acid. Additionally, certain gut microbes like Lactobacillus increased under calorie restriction and were linked to specific metabolite changes, while others like Nitrospirae decreased.

Overall, the study suggests that calorie restriction alters gut microbiota composition and metabolite levels, potentially contributing to the suppression of colorectal cancer growth.

8/ Colonic ketogenesis contributes to blood ketones and protects against colitis in mice.

The study explores the role of a gene called HMGCS2 in colonic inflammation, which can be involved in the etiology of Crohn's disease and ulcerative colitis. Researchers found decreased HMGCS2 expression in diseased tissues. Using mice models, they discovered that deleting HMGCS2 in the intestinal tract led to lower levels of ketones and increased susceptibility to colitis. This effect was more pronounced in male mice. The expression of HMGCS2 was influenced by gut bacteria. Additionally, the absence of HMGCS2 affected mitochondrial function, cholesterol balance, and gut barrier integrity. Overall, the study suggests that ketogenesis, controlled by HMGCS2, plays a crucial role in protecting against colonic inflammation, particularly in males.

9/ Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials

This review analysed evidence on intermittent fasting (IF) and its effects on health outcomes. It included data from 23 studies covering 34 health measures. Among identified outcomes, there was high certainty of evidence that decreased of waist circumference, fat mass, low-density lipoprotein cholesterol, triacylglycerols, total cholesterol, fasting insulin, and systolic blood pressure, while increased of high-density lipoprotein cholesterol and fat free mass by IF compare with non-intervention or continuous energy restriction (CER). Based on a sensitivity analysis, reduced of body mass index, fat mass, homeostatic model assessment for insulin resistance after IF intervention was graded as highly quality evidence. However, IF was less effective in reducing blood pressure compared to continuous energy restriction (CER).

10/ Yo-Yo dieting delays aging in flies

This study investigated the effects of "Yo-yo dieting" on aging in male fruit flies fed high-calorie diets. Yo-yo dieting involved alternating high and low-calorie diets every 3 days. Results showed that Yo-yo dieting extended lifespan, reduced body weight, and improved health markers compared to continuous high-calorie dieting. It also improved mitochondrial function and increased expression of proteins related to mitochondrial health. Overall, Yo-yo dieting positively influenced aging processes in fruit flies by enhancing mitochondrial dynamics and related signaling pathways.

The concept of yo-yo dieting, where individuals cycle between weight loss and regain, may have parallels in seasonal fasting. Our bodies are adapted to switch between eating and fasting, with fasting triggering regenerative processes. It's theorized that these mechanisms evolved to help animals preserve their physiology, potentially extending lifespan for reproductive opportunities under better environmental conditions. In our study of a patient who fasted seasonally for three weeks annually, we found that it was 6 years younger than his chronological age of 92. This suggests seasonal fasting might promote healthy longevity, contrasting with our uninterrupted eating habits in modern lifestyles.

And to finish with gossips, because this is more appropriate to call it that way, I can't avoid mentioning the intermittent fasting and heart health debacle.

I already wrote about this. Researchers presented data at the American Heart Association’s scientific sessions claiming a possible connection between intermittent fasting and increased risk of heart disease death. However, the analysis hasn't undergone peer review or been published in a scientific journal yet. It has been largely criticised.