Re: Time restricted eating
I found some crib notes from the first video, for those who don't have time to watch it:
_http://podcastnotes.org/2016/07/11/time-restricted-feeding-and-its-effects-on-obesity-muscle-mass-heart-health/
Dr. Satchin Panda is a professor at the Salk Institute for biological studies
Where he researches the circadian clock
What is the circadian clock and why it’s so important?
It is based on the changing environment of light during a day.
It’s particularly important for diurnal animals:
Dictates when to go to sleep and wake up.
Evolved from pressure and anticipation.
Every organ has its biological clock.
Its performance varies during the day.
Babies also have clocks, but they aren’t tied to outside light until 6 months.
Today’s top diseases are chronic.
They can be caused by an unhealthy circadian clock.
How is it related to our metabolism?
After many experiments on rodent’s brain
Scientists found the Suprachiasmatic Nucleus (SCN) located in the hypothalamus
Without it, we would have no sense of time.
It synchronises organs to activate during certain times.
What happens in the case of neurodegenerative diseases?
The SCN is damaged by the degeneration.
People lose their internal clock.
The hippocampus, which is in charge of long-term memory, is affected.
The importance of light
Light can reset our internal clock.
It adapts when seasons change and when we travel in other time zones.
Why is it blind people can’t see, but still have a clock?
Scientist found that if the eyes are taken, they loose their clock.
They discovered melanopsin, a photoreceptor, in the ganglion cells, located in the eyes.
These photoreceptors are connected to our SCN.
They are sensitive to BRIGHT light and TIME of exposure (10 000 Lux during several minutes).
Melanopsin also regulates sleep and our mood.
It suppresses melatonin, a sleeping hormone.
Melatonin they builds up during the day as the light decreases, making us sleepy when night comes.
When the sky is gray/there’s no light it can cause sessional depression.
We need more light in the first half of the day and less after noon.
Melanopsin promotes cortisol, an hormone that makes us more alert (stress hormone)
Therefore, cortisol spikes early in the morning and decreases throughout the day.
Leading a stressful life maintains our level of cortisol high, which can lead to health issues.
The role electronics play in our internal clocks
Blue light from screens and lighting send the wrong signal to the SCN.
Melatonin can’t build up.
So, someone would have trouble sleep or would wake up tired.
Philips Hue: Lights that can be programmed to send red lights instead of blue.
F.lux: Application that filters blue light and sends different shades depending on the time of day.
What about Jet Lag and night workers?
People that switch from a day shift to a night shift:
They sleep during the brightest sunlight exposure.
They rarely get exposed to the natural light.
While light does half of the work, the other half is done by food.
When traveling, light and food habits change, which messes up our SCN.
How food regulates our tissues
Internal clocks are like traffic lights: without the right timing, it creates accidents and traffic jams.
There’s a specific time for every metabolic activity.
If not properly adjusted:
There’s build up of undesired by-products.
It puts stress on our cells.
It can lead to many chronic diseases.
Our organ’s clocks respond to when we eat.
The act of eating turns on the genes responsible for digestion.
Light has little impact in that case.
The principle behind time-restricting feeding
The idea is to restrict your eating into a certain period of time, usually being 12h.
Mice that don’t have a circadian clock have greater chances of developing a metabolic disorder such as:
Obesity
Cardiovascular diseases
Diabetes
Cancer
High fat diet and high sugar diet were tested with time-restriction.
Did not matter WHAT or HOW MUCH you eat but WHEN you eat is crucial.
Mice ate the same food but the ones on time-restriction had 28% less body mass and 70% less fat.
Time restricting has a huge impact on our body.
Nutrition or quality of food still matters.
The program increased lean mass.
This can be caused by an increase in Nicotimamide Ribose, which creates more NAD.
More NAD gives more ATP.
ATP, being the main energy source of our body, boosts our energy level.
Restricting in an 8h to 9h period is even more beneficial.
It increases endurance.
An increase in brown fat tissue was noted.
There’s also an increase in mitochondria activity.
Intermittent fasting versus time-restricting feeding
In both cases, there’s a prolonged fasting period.
When we eat, we damage our cells.
Fasting promotes repairs.
Intermittent fasting restricts calories, time-restricting does not.
It’s a comeback to our primordial physiology.
The two methods are in synch with the circadian clock.
Melatonin receptors were found in pancreas.
The increase of melatonin that happens during the day inhibits insulin production.
Therefore, late night calories have different effect on our health.
_mycircadianclock.org
This site is a nutrition study application.
50% of the population eat throughout a period of 15 hours.
8 people that were asked to restrict their time.
They lost 4% body weight.
They slept better and were more energetic in the morning.
It’s an indirect way to reduce calories and eat better.
It contains two phases:
Phase 1: Collect how much and when people eat, sleep, exercise.
Phase 2: Selecting a program to follow.
It can be synched with the Health Kit and Google Fit application, which measure movement.
It’s a simple life style changes.
Experiments on fruit flies showed:
Their heart has similar genes and diseases as humans.
By following a time-restricted diet, they develop heart problem later.
They slept better and were more energetic.
The mitochondria in the heart cells were healthier.
The Electron Transport Chain (ETC) was more effective.
It also showed better proteostasis, which is important for protein folding.
Links to microbiota and digestion
Our microbiota also follows a circadian clock.
Different bacteria are active during different part of the day.
Regularity between fasting and eating allows a vast variety of species to grow.
Time-restricting changes the way sugar are digested.
It can also decrease our cholesterol level and increase the production of bile acid.
uBiome: a website where you can evaluate the changes in your gut bacteria.
liffy said:
I've been doing this for a few months, also did it for a period some years ago. It works well for me.
It might however be useful to clarify; intermittent fasting in many cases means precisely the same as this "time restricted eating". Although intermittent fasting also can mean fasting one day every now and then, the way most people use it is to shorten the eating window every day.
My understanding of intermittent fasting was that you reduce the calorie intake too. With the "time restricted eating" you have the same calories as usual.
So perhaps think of it as "eating normally" but with a longer period of time between eating from day to day.
Keyhole said:
On the topic of circadian rhythms, there are two types of circadian clocks in the body.
1. is the suprachiasmatic nuclei in the hypothalamus (the central circadian clock) which is entrained by light cycles. So light in the morning, and no light in the evening maintains this function
2. are the peripheral clocks in the CLOCK genes in peripheral cells. These are entrained by food intake. Hence, eating in the morning is important for setting peripheral clock rhythms. To add to this, eating after dark is a great way to de-synchronize the peripheral clocks (assuming one is blocking blue light at night time - which is a requirement for optimal functioning)
So, if you were eating at 7:30pm every night, this would naturally mess up your chronobiological and circadian rhythmicity. Hence, eating earlier on in the day should increase sleep quality.
I don't do any blue light restriction. I have in the past for some months, and it did improve sleep.
It didn't improve how rested I felt (i.e. still a struggle to get out of bed/no energy), how quickly my body can lose muscle mass, mood, or how I respond to keto/near keto diets.
I've read a lot of the topic of circadian rhythms, and the diet aspect was new to me (beyond not eating too late).
From what I've read/listened too, the 'peripheral clocks' are not so peripheral in my case. Given the gut and it's flora, and all visceral organs seem to be regulated by when we start eating (and are not controlled so much by light) it may be worth considering as less peripheral.
If our gut is our 'second brain' and gut flora is in control of our brain chemistry, visceral organs in charge of energy regulation and detox, could this actually be more important than light?
Good to see you are getting positive results, but what concerns me is the longer-term effects of the stress-hormone cortisol and adrenaline release in response to a fasted state. I think that you and me may be similar in some respects, Redfox. We both find it difficult to lose weight, and find it easy to lose weight if we do not maintain high caloric intake.
As has been mentioned, there is no reduction in caloric intake. I've been weighing myself every day to make sure it's not having a negative effect.
I spent some time thinking about this, as high cortisol and adrenaline would be concerning!
Given cortisol raises blood sugar I've often wondered if this is perhaps why some people don't do well with ketosis? Cortisol is breaking down muscle and causing continued elevated blood sugar, combined with mild insulin resistance and you never get into ketosis? Anyway, that's rather speculative.
So far I've gained more weight (another 1/2kg). This time significantly more muscle than body fat. I should note that I have done no exercise for about a month. If my cortisol was high would my muscle not be breaking down?
My mood is also progressively more relaxed and positive. I am taking things in my stride. Would that suggest that adrenaline isn't elevated?
So, that's subjective, so here's what I found in the way of clinical data:
_https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-1044-0
Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males
Abstract
Background
Intermittent fasting (IF) is an increasingly popular dietary approach used for weight loss and overall health. While there is an increasing body of evidence demonstrating beneficial effects of IF on blood lipids and other health outcomes in the overweight and obese, limited data are available about the effect of IF in athletes. Thus, the present study sought to investigate the effects of a modified IF protocol (i.e. time-restricted feeding) during resistance training in healthy resistance-trained males.
Methods
Thirty-four resistance-trained males were randomly assigned to time-restricted feeding (TRF) or normal diet group (ND). TRF subjects consumed 100 % of their energy needs in an 8-h period of time each day, with their caloric intake divided into three meals consumed at 1 p.m., 4 p.m., and 8 p.m. {Note the timing of the meals when considering light effecting circadian rhythm} The remaining 16 h per 24-h period made up the fasting period. Subjects in the ND group consumed 100 % of their energy needs divided into three meals consumed at 8 a.m., 1 p.m., and 8 p.m. Groups were matched for kilocalories consumed and macronutrient distribution (TRF 2826 ± 412.3 kcal/day, carbohydrates 53.2 ± 1.4 %, fat 24.7 ± 3.1 %, protein 22.1 ± 2.6 %, ND 3007 ± 444.7 kcal/day, carbohydrates 54.7 ± 2.2 %, fat 23.9 ± 3.5 %, protein 21.4 ± 1.8). Subjects were tested before and after 8 weeks of the assigned diet and standardized resistance training program. Fat mass and fat-free mass were assessed by dual-energy x-ray absorptiometry and muscle area of the thigh and arm were measured using an anthropometric system. Total and free testosterone, insulin-like growth factor 1, blood glucose, insulin, adiponectin, leptin, triiodothyronine, thyroid stimulating hormone, interleukin-6, interleukin-1β, tumor necrosis factor α, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured. Bench press and leg press maximal strength, resting energy expenditure, and respiratory ratio were also tested.
Results
After 8 weeks, the 2 Way ANOVA (Time * Diet interaction) showed a decrease in fat mass in TRF compared to ND (p = 0.0448), while fat-free mass, muscle area of the arm and thigh, and maximal strength were maintained in both groups. Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in ND (p = 0.0476; p = 0.0397). Adiponectin increased (p = 0.0000) in TRF while total leptin decreased (p = 0.0001), although not when adjusted for fat mass. Triiodothyronine decreased in TRF, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the TRF group.
Conclusions
Our results suggest that an intermittent fasting program in which all calories are consumed in an 8-h window each day, in conjunction with resistance training, could improve some health-related biomarkers, decrease fat mass, and maintain muscle mass in resistance-trained males.
From the data, the TRF groups cortisol (ng/mL) levels:
Before 174.25 ± 56.78
After 8 weeks 186.05 ± 68.5
Which was considered of no significance.
If you want to consider bio-markets, there is a huge selection of data in this paper. Along with some pretty deep research.
I am tending toward thinking that this state is due to poor thyroid function - possibly subclinical hypothyroid and excess cortisol. This can be one of the reasons why some people "feel good" in a fasted state, because they are basically running off of stress hormones. In my own case, my health went massively downhill when I went on a low-carb/ketogenic diet. I developed dandruff, serious dry skin issues, digestive/IBS symptoms, fatigue, poor circulation and food insensitivities. This fits in perfectly with stress-state metabolism and low thyroid activity. There are lots of people who report this from low-carb diets. For some people, full ketosis/low-carb/intermittent fasting seems to be perfect, but for others it can be disastrous.
I had very similar results to yourself! Which is why time restricted feeding has surprised me.
I do take your suggestion of "feeling good" possibly being stress hormones quite seriously as a result.
If fat utilization (beta oxidation)/absorption is poor, then the cell is deprived of energy. If carbohydrates are scarce, then the metabolsim is forced to switch from thyroid metabolism to the HPA axis and begin releasing cortisol which progressively breaks down muscle tissue to provide glucose for the cell to use for energy. Cortisol also suppresses thyroid hormone, which begins a feedback loop of lower metabolism. At the start, a person can feel like they have loads of energy because they are running off of stress hormones, but this gradually declines and results in muscle wasting and fatigue. What my point is, is that if someone is prone to being underweight and under chronic physiological stress, then I don't see fasting as a viable/nor safe long term option to regain proper metabolism back.
Agreed, fasting doesn't work for me. I'd see a couple of kg of weight loss and my weigh scales would tell me my muscle % had reduced considerably.
So far, the opposite is happening. Considerable muscle gain with no exercise.
I remember the C's saying something about ketosis/low carb being something that will take some people a long time to adapt to. I am under the impression that for these people (myself included), regaining proper thyroid function and metabolic efficiency should be undertaken before attempting ketosis and fasting etc. Just my thoughts, fwiw.
Well that makes sense. I did find a few papers that suggest that TRF may actually reverse some of the metabolic problems.
Of note in the second video above is mention of diabetics doing the keto diet. They could control their insulin through the diet, but fasting glucose was still sky high. TRF fixed fasting glucose.
I figure if fasting glucose is high, you'll never get into ketosis, and will be chronically stressed when NOT eating (i.e. sleeping). Glucose will crash between 2-4am and you'll wake up in a panic as your adrenals kick in to try and raise blood glucose levels.
Here are some of the papers on TRF and metabolic issues:
_http://www.cell.com/cell-metabolism/abstract/S1550-4131(12)00189-1?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413112001891%3Fshowall%3Dtrue&cc=y=
Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet
Highlights
Time-restricted feeding improves clock and nutrient sensor functions
tRF prevents obesity, diabetes, and liver diseases in mice on a high-fat diet
Nutrient type and time of feeding determine liver metabolome and nutrient homeostasis
tRF raises bile acid production and energy expenditure and reduces inflammation
Summary
While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day.
Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.
_http://journal.frontiersin.org/article/10.3389/fncel.2016.00007/full
Anticonvulsant Effect of Time-Restricted Feeding in a Pilocarpine-Induced Seizure Model: Metabolic and Epigenetic Implications
A new generation of antiepileptic drugs has emerged; however, one-third of epilepsy patients do not properly respond to pharmacological treatments. The purpose of the present study was to investigate whether time-restricted feeding (TRF) has an anticonvulsant effect and whether this restrictive diet promotes changes in energy metabolism and epigenetic modifications in a pilocarpine-induced seizure model. To resolve our hypothesis, one group of rats had free access to food and water ad libitum (AL) and a second group underwent a TRF schedule. We used the lithium-pilocarpine model to induce status epilepticus (SE), and behavioral seizure monitoring was analyzed. Additionally, an electroencephalography (EEG) recording was performed to verify the effect of TRF on cortical electrical activity after a pilocarpine injection. For biochemical analysis, animals were sacrificed 24 h after SE and hippocampal homogenates were used to evaluate the proteins related to metabolism and chromatin structure. Our results showed that TRF had an anticonvulsant effect as measured by the prolonged latency of forelimb clonus seizure, a decrease in the seizure severity score and fewer animals reaching SE. Additionally, the power of the late phase EEG recordings in the AL group was significantly higher than the TRF group. Moreover, we found that TRF is capable of inducing alterations in signaling pathways that regulate energy metabolism, including an increase in the phosphorylation of AMP dependent kinase (AMPK) and a decrease in the phosphorylation of Akt kinase. Furthermore, we found that TRF was able to significantly increase the beta hydroxybutyrate (β-HB) concentration, an endogenous inhibitor of histone deacetylases (HDACs). Finally, we found a significant decrease in HDAC activity as well as an increase in acetylation on histone 3 (H3) in hippocampal homogenates from the TRF group. These findings suggest that alterations in energy metabolism and the increase in β-HB mediated by TRF may inhibit HDAC activity, thus increasing histone acetylation and producing changes in the chromatin structure, which likely facilitates the transcription of a subset of genes that confer anticonvulsant activity.
Introduction
Epilepsy is the third most common chronic brain disorder. It affects 50 million people worldwide (Aroniadou-Anderjaska et al., 2008). Although a new generation of antiepileptic drugs has emerged, approximately 30% of epilepsy patients do not respond to classical pharmacological treatment (Löscher et al., 2013). For this reason, it is important to find new alternatives to complement pharmacological therapy in drug-resistant patients. To date, a variety of reports suggest that some metabolism-based therapies, such as ketogenic diet (KD) or calorie restricted (CR) diets, have an anticonvulsant effect (Bough et al., 2003; Stafstrom and Rho, 2012). Recently, it has been suggested that the beneficial effect of these diets may be produced by means of a metabolic shift involving the activation of AMP-activated protein kinase (AMPK), inhibition of the mammalian target of rapamycin (mTOR) and overproduction of ketone bodies (Wong, 2010; McDaniel et al., 2011; Yuen and Sander, 2014).
Time-restricted feeding (TRF) is a nutritional challenge that limits food availability to a brief time during the waking phase in mammals (Belet and Sassone-Corsi, 2010). This restrictive model induces an increase in free fatty acids (FFA) before feeding and an increase in peroxisomal markers, such as PPARα and PPARγ (Rivera-Zavala et al., 2011), suggesting that it may modulate a global metabolic shift that resembles the effects of other metabolism-based therapies.
On the other hand, environmental inputs, such as nutrition, are able to alter cell metabolism. In this sense, functional links between metabolism and epigenetic control are beginning to emerge (Sassone-Corsi, 2013). The regulation of gene expression by epigenetic modifications can occur through a variety of means. To date, the best characterized include DNA methylation, non-coding RNAs and histone posttranslational modifications (Hullar and Fu, 2014).
Histone posttranslational modifications, such as acetylation, occur at specific lysine residues and have been correlated with transcriptional activation (Sassone-Corsi, 2013). Histone deacetylases (HDACs) are enzymes that elicit the induction of repressive chromatin using specific metabolites, such as nicotinamide adenine dinucleotide (NAD+), whose availability dictates the efficacy of the enzymatic reaction (Katada et al., 2012). Interestingly, it has recently been shown that β-hydroxybutyrate (β-HB), a ketone body produced during fasting or starvation conditions, act as an endogenous inhibitor of HDACs, thus linking metabolism with gene expression (Shimazu et al., 2013).
In spite of these findings, there are no reports showing that TRF may produce beneficial effects, such as those of KD and CR, in an acute seizure model. For this reason, the purpose of this study was to determine whether TRF induces a metabolic shift by activating the energy sensor AMPK, inhibiting the Akt signaling pathway and producing epigenetic modifications that are capable of diminishing seizure susceptibility. Here, we report that TRF had anticonvulsant effects observed as prolonged latency to first seizure, a decrease in the seizure score, and a diminished number of animals that reached status epilepticus (SE). Additionally, a reduction in the power of the late phase electroencephalography (EEG) recordings in the TRF group was significantly greater than that in the AL group. Furthermore, TRF produced an increase in the β-HB concentration, activation of AMPK, inhibition of Akt kinase and increased histone 3 (H3) acetylation. These findings suggest that activation of the AMPK signaling pathway together with an increase in ketone bodies could mediate the acetylation of H3, thus contributing to the transcription of a subset of genes conferring anticonvulsant activity.
_http://www.sciencedirect.com/science/article/pii/S1550413114004987
Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges
[..]
Diseases like obesity, arising from nutrient imbalance or excess, are often accompanied by disruptions of multiple pathways in different organ systems. For example, the regulation of glucose, lipids, cholesterol, and amino acids (aa) homeostasis involves the liver, white adipose tissue (WAT), brown adipose tissue (BAT), and muscle. In each tissue, nutrient homeostasis is maintained by balancing energy storage and energy utilization. Pharmacological agents directed against specific targets effectively treat certain aspects of this homeostatic imbalance. However, treating one aspect of a metabolic disease sometimes worsens other symptoms (e.g., increased adiposity seen with insulin sensitizers), and beneficial effects are often short lived (e.g., sulfonylureas) (Bray and Ryan, 2014). Furthermore, recent studies have shown that early perturbation of nutrient homeostasis can cause epigenetic changes that predispose an individual to metabolic diseases later in life (Hanley et al., 2010). Hence, finding interventions that impact multiple organ systems and can reverse existing disease will likely be more potent in combating the pleiotropic effect of nutrient imbalance.
[..]
Recent discoveries have shown that many metabolic pathways, including current pharmacological targets, have diurnal rhythms (Gamble et al., 2014 and Panda et al., 2002). It is hypothesized that under normal healthy conditions the cyclical expression of metabolic regulators coordinates a wide range of cellular processes for more efficient metabolism. In HFD-induced obesity, such temporal regulation is blunted (Kohsaka et al., 2007). Tonic activation or inhibition of a metabolic pathway, as is the case with pharmacological therapy, cannot restore normal rhythmic activity pattern. Therefore, interventions that restore diurnal regulation in multiple pathways and tissue types might be effective in countering the pleiotropic effect of nutrient imbalance.
Gene expression and metabolomics profiling, as well as targeted assay of multiple metabolic regulators, have revealed that a defined daily period of feeding and fasting is a dominant determinant of diurnal rhythms in metabolic pathways (Adamovich et al., 2014, Barclay et al., 2012, Bray et al., 2010, Eckel-Mahan et al., 2012 and Vollmers et al., 2009). Accordingly, early introduction of time-restricted feeding (TRF), where access to food is limited to 8 hr during the active phase, prevents the adverse effects of HFD-induced metabolic diseases without altering caloric intake or nutrient composition (Hatori et al., 2012).
Hypothetically then TRF regulates the visceral circadian rhythm (through food, not light) and
may be able to counter early epigenetic changes in energy metabolism. fwiw
