Recent Research on Fasting and Calorie Restriction (June 2024, part 1)

This is only the part 1 of the interesting studies I have collected for June 2024. Part 2 is coming soon, but I have parenting duties I must prioritise ??

1/ Our new study on ketosis during long-term fasting

In case you haven't seen my posts on this new study, we monitored 1610 participants undergoing the Buchinger Wilhelmi fasting program (4-21 days, 75-250 Kcal daily). We examined fasting ketonemia (blood ketones) and ketonuria (urine ketones), and compared these values to the metabolic improvements the patients experienced. ?Key findings:

1??Long-term fasting induced ketosis safely from day 2 in most patients.

2?? Minimal carbohydrate intake with juices and honey modulated but did not suppress ketosis.

3?? We could predict if patients have weak or strong ketosis based on what the patients did in the clinic, the supplements they took, or their age, gender, physiological status.

4?? Patients with the strongest ketosis had greater reductions in blood glucose, glycated hemoglobin, body weight, and waist circumference.

5??Patients with the strongest ketosis had a better antioxidant status than patients with low ketonuria via the increase in uric acid.

2/ Exploring the effect of prolonged fasting on kynurenine pathway metabolites and stress markers in healthy male individuals

This study explored how fasting for six days affects certain chemicals in the body related to stress and metabolism in healthy men. Researchers found that fasting increased levels of specific metabolites (picolinic acid, kynurenic acid, and 3-hydroxykynurenine) while decreasing others (tryptophan and quinolinic acid). Despite these changes, stress markers like cortisol and noradrenaline remained stable, although adrenaline levels rose. Normal diet restored metabolite levels quickly after fasting.

The stress response causing adrenalin levels to rise during fasting is an ancestral response which pushes us to be more energetic to find some food.

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3/ Brain Responses to Intermittent Fasting and Healthy Living Diets in Older Adults

Interesting new study by Pr. Mark Mattson and colleagues

A 8-week randomized clinical trial with 40 older adults with insulin resistance compared 5:2 intermittent fasting (IF) to a healthy living diet. IF led to more weight loss, while both diets reduced neuronal insulin resistance, slowed brain aging, and improved memory and executive function, with IF showing greater cognitive benefits. No significant changes were observed in Alzheimer’s disease biomarkers with either diet.

?? Important limitations (my opinion): I would be curious to know if both groups had consistent eating windows or if the IF group somehow binged after their fasting days, and what would be the effects if the IF was actually water fasting and not getting protein shakes.

But without being too harsh it is still a very good study because it is very difficult to control so much people’s diet!

Anyway I always found the idea of 5:2 strange because it gets the body into the zone where the fasting metabolism is not established, with the body extremely relying on gluconeogenesis, disturbing circadian rhythms, and then food consumption is resumed before people get in the zone where there are benefits of long-term fasting… Time restricted eating and more rare but longer periods of fasting are more promising!

4/ Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy

Calorie restriction (CR) extends health and stress resilience in aging by enhancing chaperone-mediated autophagy (CMA), a process that maintains protein quality. Aging reduces CMA due to lower levels of the protein LAMP2A. This study shows that CR and CR-mimicking drugs boost CMA in older mice by stabilizing LAMP2A, improving stress responses. These findings suggest targeting CMA could be beneficial for aging-related therapies.

Interestingly, calorie-restriction mimetics like spermidine, a new compound called C646, hydroxycitrate, and the new-generation compound SB20499 also worked quite well in mimicking these effects.

5/ Rejuvenation of stem cells by fasting depends on the food reintroduction

As we age, the stem cells in our blood, which are responsible for creating red blood cells and all the cells of our immune system, become less effective. One way to rejuvenate these old blood stem cells is fasting, which triggers autophagy. In this new study at Columbia University, fasting in mice helped reset stem cell function, making them almost as effective as young stem cells in regenerating the blood system and producing new blood cells. The effects were not triggered by fasting alone, but by fasting plus resumption of eating.

At the Clinic Buchinger Wilhelmi I The Fasting Experts, we have seen that caution in reintroducing food after fasting is crucial for achieving the full benefits. I often tell patients that ending the fast is not the end of the therapeutic journey. It’s like the end of winter for the body, and now it’s time for Spring with cell regeneration.

6/ Assessment of Advanced Glycation End-products (AGEs) and their receptors (RAGE) in obese patients treated by moderate caloric restriction combined with physical activity

This study looked at proteins related to inflammation in lean and obese people. Advanced Glycation End-products (AGEs) and their receptors (RAGE) play a role in inflammation. RAGE has different forms: soluble RAGE (sRAGE), endogenous secretory RAGE (esRAGE), and cleaved RAGE (cRAGE). EN-RAGE is a protein that binds to RAGE and promotes inflammation.

In obese patients, sRAGE and esRAGE levels were lower, while EN-RAGE levels were about three times higher than in lean individuals. After three weeks of moderate calorie restriction and exercise, inflammation markers improved, shown by lower EN-RAGE levels, but sRAGE and esRAGE levels did not increase significantly.

Obese patients before and after calorie restriction had higher AGE concentrations when compared to lean control. Three weeks of calorie restriction with physical activity was not able to correct the obese AGEs value to those observed in the control group.

7/ Acrolein-triggered atherosclerosis via AMPK/SIRT1-CLOCK/BMAL1 pathway and a protection from intermittent fasting

This study reveals that circadian rhythm disruption contributes to heart disease progression. Acrolein, a pollutant, worsens artery hardening by disturbing CLOCK/BMAL1 proteins. However, intermittent fasting (IF) can counteract these effects. Mice on acrolein showed increased inflammation markers, but IF reduced these and boosted beneficial proteins (AMPK, SIRT1). Additionally, IF restored disrupted circadian genes, highlighting its potential to prevent heart disease by improving circadian function and reducing inflammation.

8/ Caloric restriction can also extend the lifespan of plants

Caloric restriction (CR) can extend the lifespan of clonal plants, just like it does in animals. In this study, reducing light intensity (which limits photosynthesis and thus calories) for the aquatic plant Lemna minor significantly increased its lifespan. The results suggest that both plants (autotrophs) and animals (heterotrophs) benefit from CR, with light intensity having predictable effects on plant aging.

9/ Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction

The study compared two weight loss diets: intermittent fasting combined with protein pacing (IF-P) and continuous calorie restriction (CR). Protein pacing involves eating small, protein-rich meals throughout the day. Here, four meals/day were consumed evenly spaced every 4 h, consisting of 25–50 g of protein/meal.

IF days consisted of ~350–550 kcals per day, in which participants were provided a variety of supplements and snacks. In comparison, participants assigned to the CR diet had <35% of kcal as fat. The total calorie intake was 1200 and 1500 calories per day for women and men, respectively, during the 8-week weight loss intervention.

The study found that IF-P improved gut health, increased beneficial gut bacteria (Christensenellaceae), enhanced fat-burning molecules, and reduced inflammation more effectively than CR. Both diets influenced weight loss and body composition through different gut and metabolic changes, suggesting tailored nutrition strategies could enhance health and weight management.

I find the comparison between these two diets very strange, because so many parameters were varying at the same time (quantity of calorie, macronutrient distribution and meal timing). I find it hard to conclude anything about what is best here.

10/ Dietary restriction in mice improves muscle quality, maintaining strength and coordination

Sarcopenia, the loss of muscle mass and function in elderly people, lacks effective treatments. This study found that dietary restriction (kcal restriction increased weekly by 10%, until it reached 30%) in mice reduces body weight and muscle mass but improves muscle quality, maintaining strength and coordination. Using advanced techniques, researchers discovered that dietary restriction decreases harmful stress and inflammation in muscles while increasing beneficial energy production processes. These findings may help in diagnosing, preventing, and treating sarcopenia.?

Would the findings be the same for humans fasting 12 days at the Buchinger Wilhelmi Clinic ? I am going to tell you very soon !

As usual feel free to comment, raise any questions, or simply like or repost this new issue in order to raise awareness about the science of fasting!