"Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges"
http://www.cell.com/cell-metabolism/pdf/S1550-4131(14)00498-7.pdfBrilliant. Something I've written about (more than once) and many have probably heard me speak about is finally starting to get further elucidation and light on its benefits.
It's about time-restricted feeding aka intermittent fasting. There have been several studies to demonstrate its benefits over time, however, particularly robust studies have surfaced as of late, allowing further molecular insight governing them, as well as general mechanistic benefits (though a lot still needs to be done).
So, simplifying the matter, it can be said that restricting the eating window to a specific time period (ie 6-12 hours, 12 hours of fasting/eating being the minimum) is largely ameliorative for various biochemical health markers such as plasma cholesterol and triacylglycerols, blood glucose and insulin sensitivity, cognitive decline with age, inflammation, and more.
The study demonstrates that utilizing intermittent fasting, even on an equivalent diet compared to an ad libitium (anytime) protocol still harbors the benefits. This helps show there's much more important factors than the ignorant dichotomy of "clean" vs "dirty" foods, such as eating by your circadian rhythm (biological clock - field of chronobiology) and having a good balance in your respective anabolic/catabolic pathways via diet-induced physiology (think metabolic see-saw of mTOR vs AMPK).
I thought I'd take a moment to discuss some of the high points of this study, as well as give some of my own personal thoughts/implications and some explanations.
This study noted, in the intermittent fasting groups, an attenuation of body weight/fat mass, as well as a general protection from body fat gain. They noted lower insulin levels and greater insulin sensitivity/glucose tolerance. They noted improved lipid & cholesterol homeostasis (reduced plasma TAGs & cholesterol), exercise performance, mitigated inflammation, diminished liver fat accretion (hepatic steatosis), and protein synthesis capacity (via p70s6k expression & phosphorylation).
Now, a major regulator of our circadian rhythms is the expression of Sirt1, which regulates central circadian control at the suprachiasmatic nucleus in the hypothalamus (the central/"master" clock). Sirt1 expression is reduced in obesity and aging, which disrupts the synchronicity of the clock and entrainment to light & feeding schedules causing metabolic derangement. However, short-term fasting/time-restricted feeding increases its levels, which may underlie much of this study's benefits.
Another mechanism may involve the transcription factor CREB, which is upregulated in many tissues during fasting via increased signaling of norepinephrine/epinephrine, glucagon, and et cetera. Its expression plays an integral role in entraining our central clock to a rhythm.
This study noted attenuated inflammation through a reduction in various pro-inflammatory cytokines (such as TNF-alpha and IL-1beta). This is likely through an increase in HDAC4. Other studies have found HDAC4 is increased during fasting, due to a PKA-mechanism (so the norepinephrine/glucagon and such signaling through cAMP pathways will employ this), which directly impedes binding of NFkB (a transcription factor that causes expression of pro-inflammatory cytokines) to the promoter of genes.
Following with inflammation, through metabolomic studies they showed a protection against reactive oxygen species (ROS). This is likely mediated via NRF2 and FoxO, both of which have been shown to be upregulated in fasting. They are huge mediators of a mitohormetic response (of which fasting induces), which increases stress-resistance and upregulates our endogenous antioxidant capacity. This pathway is hugely beneficial.
The lipid & cholesterol metabolism they noted is due to decreased PPAR-gamma in many tissues, indicating decreased fat storage, and increased in other tissues, which has been shown to play a protective role in cholesterol and lipid homeostasis (eg. macrophages/foam cells), increased PGC-1 alpha levels, which increases the lipid oxidation (fat burning), as well as many other benefits the study didn't touch on such as increased mitochondrial efficacy and even a likely mechanism to reduce depression via shifting the metabolism of kynurenine. The cholesterol homeostasis was mediated by increases in the active form of SREBP and an increased synthesis of bile acids, utilizing more cholesterol.
As far as protein synthesis capacity and general protein metabolism is concerned, they actually noted an increased level of circulating amino acids in the ad-libitium groups, and an increased expression of p70s6k in the fasting group (thus also decreased circulating AAs). This is pretty exciting as it seems to hint at greater protein synthesis and AA utilization when giving your body adequate time to fast, despite an elevation in some catabolic factors. The ad-libitium group also had elevated levels of gluconeogenesis, which shows the elevated circulating AAs are likely being more-so utilized there to convert into glucose, dampening available substrate for protein synthesis. I would really like for something similar to be studies in humans as it's still so ubiquitously pontificated in the lifting community that you need to eat more frequently to stimulate protein synthesis.
Another really intriguing aspect of this study, worth bringing attention to, is that mice that were on a varied paradigm, whereby during the week they intermittently fasted (time restricted feeding) and during the weekend they ate ad-libitium. Well, the benefits and gene expression of the fasted mice were sustained with this model, even when the mice were sacrificed during the weekend.
Moreover, switching mice from a chronic ad-libitium diet to a time-restricted one ameliorated the health status of existing obesity and helped shed body fat.
I'll stop here as I've written quite a lot about this before from a different perspective and most of the high points I touched upon. Furthermore, this study did present some new data and all the previous data on this topic corroborates these findings. There's also quite a few studies on metabolic synchronization of the circadian clock, though most of it is still too nebulous to really give a concrete recommendation. I'm elated to see more delineation on the nuances of time-restricted feeding though. I think one thing is assured and that's staying consistent with your dietary habits.
Sorry for the long and random post, but I'm hoping to help people improve themselves through expanding knowledge, so if I could even help 1 person, it's worth it.
Happy fasting
