Fasting And Stem Cell Function

In mice, a 24 hour fast improves the function of intestinal stem cells through effects on fatty acid oxidation (FAO).  Genetic knockout experiments emphasize the importance of FAO in the fasting effects and suggest possibilities for boosting intestinal stem cell regeneration.  Abstract:

Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration.

High Fat Diet And the Aging Mouse Brain

A high fat diet seems not to be very good for aging of the mouse brain.  Fasting and a low fat diet seemingly have different effects.  Abstract:

Fasting may be exploited as a possible strategy for prevention and treatment of several diseases such as diabetes, obesity, and aging. On the other hand, high-fat diet (HFD) represents a risk factor for several diseases and increased mortality. The aim of the present study was to evaluate the impact of fasting on mouse brain aging transcriptome and how HFD regulates such pathways. We used the NCBI Gene Expression Omnibus (GEO) database, in order to identify suitable microarray datasets comparing mouse brain transcriptome under fasting or HFD vs aged mouse brain transcriptome. Three microarray datasets were selected for this study, GSE24504, GSE6285, and GSE8150, and the principal molecular mechanisms involved in this process were evaluated. This analysis showed that, regardless of fasting duration, mouse brain significantly expressed 21 and 30 upregulated and downregulated genes, respectively. The involved biological processes were related to cell cycle arrest, cell death inhibition, and regulation of cellular metabolism. Comparing mouse brain transcriptome under fasting and aged conditions, we found out that the number of genes in common increased with the duration of fasting (222 genes), peaking at 72 h. In addition, mouse brain transcriptome under HFD resembles for the 30% the one of the aged mice. Furthermore, several molecular processes were found to be shared between HFD and aging. In conclusion, we suggest that fasting and HFD play an opposite role in brain transcriptome of aged mice. Therefore, an intermittent diet could represent a possible clinical strategy to counteract aging, loss of memory, and neuroinflammation. Furthermore, low-fat diet leads to the inactivation of brain degenerative processes triggered by aging.

One can speculate about the human situation.

Intermittent Fasting Problem?

While there are a number of studies supporting benefits for of intermittent calorie restriction (ICR), a disturbing new study in mice suggests negative effects of ICR: an increase in cancer stem cells (CSCs) and enhancement of epithelial to mesenchymal transition, which promotes metastasis.  Keeping the mice in “continuous calorie restriction had no effect on tumor weight, metastasis, or the number of CSCs in tumors or blood” – not bad but not good either.  Speaking for myself, I eat three healthy meals per day (with approximately 12 hours between dinner and the subsequent breakfast), avoid overweight/obesity, and avoid any “fad diets.”  That’s what I’m doing, that is not necessarily a recommendation to anyone else.  Abstract:

The effect of intermittent calorie restriction (ICR) on cancer is controversial. In this study, we examined the effects of ICR and food content in syngeneic BALB/c mice injected with CT26 mouse colon cancer cells. Mice were subjected to 24-h fasting once a week for 4 weeks, and then provided with a control, high-calorie, or trans fatty acid-rich diet. While ICR resulted in increases in tumor weights, metastasis and in the number of cancer stem cells (CSCs) in the tumors or blood of mice fed the control and high-fat diets, it had no effect on body weight after 4 weeks. In particular, we detected increases in the numbers of CSCs in the tumor or blood on the day after starvation, when food overconsumption was detected. Conversely, continuous calorie restriction had no effect on tumor weight, metastasis, or the number of CSCs in tumors or blood. In the post-starvation period, energy metabolism in the tumor was altered from oxidative phosphorylation to glycolysis/lactate fermentation, with the acquisition of the epithelial-mesenchymal transition (EMT) phenotype. Hyperglycemia at the post-starvation period induced the expression of insulin-like growth factor-1, hypoxia-induced factor-1α and Nanog, as well as the phosphorylation of Stat3. Taken together, these findings suggest that ICR induces an increase in the number of CSCs and enhances EMT by promoting the Warburg/Crabtree effect following post-fasting food overconsumption.

Four Approaches To Weight Loss

By FatM1ke - Central_Obesity_011.jpgCentral_Obesity_008.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4412552

Here is a review paper on weight loss that focuses on four methods: (1) juicing/detoxification, (2) intermittent fasting, (3) paleo, and (4) high intensity training.  The first three methods all led to weight loss due to caloric restriction; however, the extreme “fad diets” of juicing or detoxification lead to weight gain when the normal diet is resumed. Paleo, if followed continuously, would seem to enable the weight to be kept off; the basic lesson is that a diet needs to be a sustainable, long-term commitment, not a short-term extreme such as, for example, juicing. Intermittent fasting also can work if followed on a regular basis.  I myself cut back on saturated fat, “junk” food and excess sugar, while increasing fruit, whole grains, and vegetables (with one “cheat day” in which I really don’t eat that unhealthy either).  Caloric restriction is what all have in common.  Interestingly, “high intensity training” worked as well, despite the recent paradigm that says that weight loss is overwhelmingly about diet and not exercise (the latter of which has a host of other benefits). Perhaps the type of exercise is important, and one wonders if all variables are taken into account; perhaps those who do “high intensity training” have healthier diets.  Abstract:

PURPOSE OF REVIEW:

The purpose of this paper is to review the epidemiology of obesity and the most recent literature on popular fad diets and exercise regimens that are used for weight loss. The weight loss plans that will be discussed in this article include juicing or detoxification diets, intermittent fasting, the paleo diet, and high intensity training.

RECENT FINDINGS:

Despite the growing popularity of fad diets and exercise plans for weight loss, there are limited studies that actually suggest these particular regimens are beneficial and lead to long-term weight loss. Juicing or detoxification diets tend to work because they lead to extremely low caloric intake for short periods of time, however tend to lead to weight gain once a normal diet is resumed. Both intermittent fasting and the paleo diet lead to weight loss because of overall decreased caloric intake as well. Lastly, studies on short bursts of high intensity training have shown remarkable weight loss and improvements in cardiovascular health. Review of the literature does suggest that some fad diets and exercise plans do lead to weight loss; however, the studies are quite limited and are all based on the concept of caloric restriction.

Body Composition And Diet

Protein shake on left.  By Sandstein - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=6068429

Here’s an article on body composition and diet.  Note that points 4 and 6 are consistent with mainstream bodybuilding advice, which is reassuring because many people have been following that advice (but note that diets very high in protein can be rough on the kidneys over time, so caveat emptor. Points 1-3 are consistent with common sense (also reassuring).  Point 5 should also be common sense, but is a necessary antidote to those who fixate that their particular form of dieting is “best for everyone” rather than just best for them.  Point 7 falls into the same boat; both methods (intermittent vs daily caloric restriction) can be useful for folks who want to lose weight. Point 8 makes sense – dietary success may depend on mitigating the adaption of the body to the diet, and point 9 is that more study is required. Abstract:

Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature regarding the effects of diet types (macronutrient composition; eating styles) and their influence on body composition. The ISSN has concluded the following. 1) There is a multitude of diet types and eating styles, whereby numerous subtypes fall under each major dietary archetype. 2) All body composition assessment methods have strengths and limitations. 3) Diets primarily focused on fat loss are driven by a sustained caloric deficit. The higher the baseline body fat level, the more aggressively the caloric deficit may be imposed. Slower rates of weight loss can better preserve lean mass (LM) in leaner subjects. 4) Diets focused primarily on accruing LM are driven by a sustained caloric surplus to facilitate anabolic processes and support increasing resistance-training demands. The composition and magnitude of the surplus, as well as training status of the subjects can influence the nature of the gains. 5) A wide range of dietary approaches (low-fat to low-carbohydrate/ketogenic, and all points between) can be similarly effective for improving body composition. 6) Increasing dietary protein to levels significantly beyond current recommendations for athletic populations may result in improved body composition. Higher protein intakes (2.3-3.1 g/kg FFM) may be required to maximize muscle retention in lean, resistance-trained subjects under hypocaloric conditions. Emerging research on very high protein intakes (>3 g/kg) has demonstrated that the known thermic, satiating, and LM-preserving effects of dietary protein might be amplified in resistance-training subjects. 7) The collective body of intermittent caloric restriction research demonstrates no significant advantage over daily caloric restriction for improving body composition. 8) The long-term success of a diet depends upon compliance and suppression or circumvention of mitigating factors such as adaptive thermogenesis. 9) There is a paucity of research on women and older populations, as well as a wide range of untapped permutations of feeding frequency and macronutrient distribution at various energetic balances combined with training. Behavioral and lifestyle modification strategies are still poorly researched areas of weight management.

Diet and cancer, again

The wording in the video is not quite scientific; however, the message is true. Watch if you or someone around you has cancer:  The Ketogenic Diet and Cancer. 
I have previously written about the benefits of both, ketogenic diet and intermittent fasting.

Real feeding frenzy

Today I am not writing about the ($)-feeding frenzy;  I am not discussing intermittent fasting either, as it is clear that the opposite trend, this of a non-stop feeding frenzy is vastly more popular. This frantic behavior is exhibited everywhere, but  it is most evident at the U.S. airports, the movie theaters, and even at our jobs.

For the past 20 years I have spent considerable time waiting for my flights at the U.S. airports. Every time I enter an airport I am shocked by the waiting lines and crowds of people in front of the restaurants. Frequently, there is not a single free table at these places. In fact, the only really long waiting lines I have seen in the U.S. are those in front of airport restaurants (OK, I admit, I have never participated in a Black Friday madness, I rather celebrate Buy Nothing Day). It almost seems that the passengers had been warned that once on the planes, they would be dangerously starved. As a result, any spare time before boarding is dedicated to accumulating more and more calories. Meanwhile, it seems that I might be the only lunatic who is crisscrossing the airport to “keep in shape”. Well, there are also other reasons not to join the gourmet orgy: I am cursed with bloating when flying, and I am reluctant to use the plane bathrooms. So, while I abstain, thousands around me are gorging and stocking up with snacks for the plane. Anyway, at least one person was happy about me being “weird”: last time I boarded a plane, the passenger next to me smiled, and said that it was great to be seated with a normal-weight person. I just nodded.

The situation in our movie theaters is also illustrative. As soon as the movie goers are inside the theater, they flock at the concession stand, and stock up with huge containers of food and drinks. The amount of food a single person gobbles down during a movie may sustain a third-world person for 2-3 days. The impression is that seeing a movie equals to an exhausting expedition to the harsh and unforgiving surroundings…of the movie salon. Clutching huge cups and bags of food, the viewers settle in the artificially created darkness, and only the tactile and olfactory senses allow the courageous people to find their nourishment and prevent the thirst/hunger-induced demise.

Finally, there have been job meetings and workshops, at which my colleagues have been offered or not offered food, and there have been very strong responses to both situations. Situation (A), this of “no food during the meeting” has elicited a strong sense of indignation and even grief. It has been discussed that one- to three-hour meetings are a substantial drain of energy (i.e., involving exertion by sitting and listening to someone else talking) and is therefore, inadmissible inhumane treatment. The second scenario (B) of “food during the meeting” is usually employed by the organizers to secure at least some attendance, and such situations turn the meetings into a lively practice of gorging on anything edible. The talk/discussion at the meeting takes on a secondary role, and it becomes irrelevant to the main activity of eating.

So, there you have it – we have turned into a nation that does not stop eating. Almost nothing can prevent us from doing it.

This one did not want to eat!

More on intermittent fasting and reduced calorie intake

In October 2015, I posted on the ability of intermittent fasting (i.e., the regimen in which food intake is limited within six to eight hours for each 24 hours) to counteract cancer progression. The likely mechanism is the depletion of glucose, which is a primary source of energy for some (but not all) cancer cells. 

Intermittent fasting, however, has more benefits. Here is what I have found so far: 

• Intermittent fasting allows for a renewal of our immune system. It has been established that fasting promotes the regeneration of hematopoietic stem cells, which are responsible for the production of our immune cells. 

•  Reduced calorie intake decreases metabolism and attenuates telomere erosion; both effects may protect cells from DNA damage and therefore, from aging and cancer. I have previously written on the connection between telomere length and cancer risk. It remains to be seen, however, whether intermittent fasting without calorie restriction has the same benefits.

• Fasting counteracts inflammation, because it contributes to the generation of metabolites such as hydroxybutyrate (a ketone body) and lactic acid. It has been documented that these molecules bind receptors on macrophages, and suppress inflammation.

• Intermittent fasting can reduce acne by suppressing inflammation-associated signaling pathways (some of which are induced by our diet).

The bottom line is that the same way lean spending is good for your net worth, being lean on calorie intake boosts your health.