These dudes ate a ton of sat fats and nothing bad happened

Study: 12 weeks, obese men, very high fat low carb (VHFLC) vs. low fat high carb (LFHC) (Veum et al., 2016) #FATFUNC

 

Pictorially:

 

 




 

It wasn’t explicitly AD LIB, but pretty close.  I say this because that is the magnitude of appetite decline we might expect when people go on The Hunger Free Diet(s), eg,

 

^^^ GOOD IDEA

 

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LIGHT is a drug

Three stories about LIGHT

One

Carbon monoxide (CO): one of the nasty things in car emissions & cigarette smoke.  Also, a byproduct of the ever-important heme.  Heme, as you may recall, activates Rev-erb:

 

“Food for thought: an endogenous ligand of Rev-erb is heme (the iron-binding element in red blood cells).  Heme is degraded into bilirubin.  Elevated levels of bilirubin cause jaundice.  A treatment of neonatal jaundice is exposure to blue light.  Blue light is a major regulator of circadian rhythms and Rev-erb is an executive-level player in this game.  The primary mechanisms of blue light appear unrelated in these two models (melanopsin activation vs. bilirubin photoisomerization), but seem intertwined, because heme activates Rev-erb.  Cool.”

 

News: Disruption of the body’s internal clock causes disruption of metabolic processes

Science: Reciprocal regulation of carbon monoxide and the circadian clock (Klemz et al., 2016)

Tl;dr: heme degradation occurs on a circadian cycle and produces CO.  CO prevents Clock/Bmal1 from binding to DNA. Inhibiting this process throws off numerous other circadian rhythms in the liver.

SUNLIGHT and food in the morning, and let endogenously produced CO rhythmically tune the clock in the evening.

 

 

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Ketones inhibit lipolysis

Petro just posted a brief article about acipimox & the insulin hypothesis.  Similar to insulin’s forte, acipimox inhibits lipolysis.  This leads to expansion of adipose tissue, and eventually, weight gain.

Acipimox acts on the same receptor as niacin and ketones, GPR109a.  That is, all three of those agents inhibit lipolysis.  We’ve discussed some of the implications of this on fuel partitioning HERE.

 

ketone-supp-physiology

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If meat causes cancer…

Disclaimer: I’m meat-cancer agnostic.  *IF* meat causes cancer (and I don’t think it does), it happens extremely slowly and only at very high levels of intake: to get statistically significant risk ratios, researchers usually look to top vs. bottom quartiles, which is quite a large difference in intake.

Meat-cancer studies Tl;dr: some studies show positive associations, some neutral, and none are negative (ie, it’s unlikely meat prevents cancer).

That said, if meat does cause cancer, here is how it might happen:

1. The “Maybes:” AGEs, leucine/mTOR, methionine, etc., but only in combination with numbers 2 & 3.  Not by themselves.

2. Circadian arrhythmia and cancer: potential mechanisms

3. Most animal foods have a lot of linoleate 18:2n6 or at least a lot more n6 than n3 (grass-fed is usually a little better in this context).  More on this below.

 

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VEG*N

I’m not vegan but the “Anti-Vegan Because B12” argument is lame.  B12 insufficiency is largely due to malabsorption, not steak deficiency.

Many people take supps, but somehow anti-vegans think B12 invalidates veganism.  It doesn’t.  Also, 1) tons of B12 in oysters; 2) nori B12 works in humans and rats; and 3) mushrooms still haven’t been ruled out as a legit source.  Whether you consider these foods vegan or not is a different story.  Many non-vegans are B12-deficient, too -> all the steak in the world won’t help if you can’t absorb it.

I’m not undermining the severity of B12 deficiency, just noting some basic facts.

My bias: things like T2DM, obesity, and even some cancers and mood disorders are due primarily to circadian arrhythmia, sleep, & LIGHT… and secondarily to diet.

When it comes to diet, mostly plants plus some animal is optimal for humans in our modern #context, regardless of which Ice-Age Paleo-Fairy Tale™ you subscribe to.  Things like sleep, LIGHT, and activity, among others, seem way more important than debating historical [theoretical] dietary minutiae.

Lastly, this particular debate isn’t “vegan vs. keto.”  THEY’RE NOT MUTUALLY EXCLUSIVE.  “Eco-Atkins” is a thing.  Animals provide a convenient source of LC protein, but it can be done without them.

 

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The poor, misunderstood autophagy

Autophagy isn’t a big deal in the way some Internet Bro’s think it is.  Yes, Dr Ohsumi received a Nobel Prize for cracking deeply into this nut, but that in no way means “intermittent fasting is awesome because autophagy.”  Autophagy isn’t awesome like that.

Alternate title: The dark side of autophagy.

For example: Autophagy contributes to muscle wasting in cancer cachexia (Penna et al., 2013)

Cachexia (muscle wasting) is one of the leading contributors to poor quality of life in cancer patients.  Thanks, autophagy.

“Autophagy is the major process for degradation of cellular constituents, its rate being enhanced under stress conditions leading to organelle damage…”

 

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The Hunger-Free Diet(s)

It started out as “lose weight without hunger on LCHF” and went all the way to “effortless fasting on keto.”  Works for some and it might be true, but the same can be said for low fat diets!  The key, I think, in both contexts, is simple: fewer processed & refined foods… something the Paleo movement got right, imo (although I still think many low-calorie sweeteners are way less unhealthy than HFCS & sugar).

The logic:

1) add “good calories” like almonds to your diet and appetite spontaneously compensates by eating less other stuff: energy neutral

2) you don’t compensate for added “bad calories” like sugar-sweetened beverages: positive energy balance

3) remove bad calories from your diet and you don’t compensate by eating more other stuff: negative energy balance

 

Book: Good Calories, Bad Calories

 

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Circadian rhythms and cancer: potential mechanisms

Humans are incredible omnivorous beasts that can thrive on a great variety of diets, but crumble if you mess with their sleep.

Circadian arrhythmia is thought to be a driving force behind a few types of cancer.  But how, exactly, does seemingly harmless things like artificial light, skipping breakfast, or jet lag actually promote tumorigenesis?  There are many potential mechanisms, and I’d bet different circadian disruptions promote different cancers in different #contexts.

In some cell types, circadian disruptions which dampen amplitude increase proliferation.  This has led to some researchers to believe a robust circadian rhythm per se is tumor-suppressive.  In agreement with this, many tumor suppressors are direct targets of circadian transcription factors.  As was observed in some skin cancers, you may want suppressed proliferation at some times of the day but not others, so the tissue can renew properly.  But you don’t want, for example, skin cells to be proliferating while they’re being exposed to UV light, so this process happens at night (in circadian fashion).

Circadian transcription factors also directly interact with endogenous antioxidant systems.

 

circadian-image

 

Cancer clocks out for lunch: disruption of circadian rhythm and metabolic oscillation in cancer (Altman, 2016)

 

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Non sequiter dietary fats

Tl;dr: SFA and DHA

Essential fatty acids?  Well, there’s really only one, DHA, and we really only need a gram or two.  In other words, our entire requirement for dietary fat can be met by about 2% of total calories (plus a few extra grams to accommodate fat-soluble vitamins) (plus DHA is never the sole fat in a food, so you’d be getting a few more grams of other fats, too).  But still, a very low fat diet!  But impractical and probably not very palatable or healthy.

On average, dietary fat comprises about a third of calories, roughly equally divided between SFA, MUFA, and PUFA (slightly less PUFA).

Major sources of SFA are pizza and desserts – no wonder SFA gets a bad rap!

 

cheese-crust-pizza

 

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Autophagy

Caloric restriction (CR) activates autophagy.  Intermittent fasting (IF) is basically kind-of-like the opposite of CR.  I’m not knocking IF.  The animal studies of autophagy, based on “chronic nutrition depletion,” more accurately reflect CR which results in decreased body weight or metabolic rate.   IF generally includes refeeds, resulting in weight maintenance.  Also, in the few human studies on it, weight loss (CR) but not fasting (IF) has been shown to induce autophagy.

If you’re actually losing weight over the long-term with an IF protocol, and thus are CR by definition, then I suspect you may be autophaging, too (yeah yeah, I know, that’s not really how autophagy works, but you get the picture).

Disclaimer: I’m relatively autophagy-agnostic; not really confident racing to maximize it is a great thing based on Human Studies.

Book: Autophagy in Health and Disease

 

autophagy-image

 

Exhibit A: autophagy in skeletal muscle

Tl;dr: “a little exercise is a better than a lot of fasting”

A1) Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle (Moller et al., 2015)

The protocol: participants either fasted for 36 hours or received a glucose infusion before and during exercise (cycling at 50% max for an hour).

“In the present study, we demonstrate that short-term aerobic exercise activates autophagic signaling through ULK1 in human skeletal muscle, independently of nutrient background.”

They really should’ve stressed that the deck was stacked to show fasting activated autophagy… 36 hours of fasting is pretty long but it had no effect.

 

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