Author Archives: Bill

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.

Also, oysters SMOKE meat for B12. Seriously, over a full day’s supply in one medium-sized oyster. Can meat do that?

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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Circadian rhythms and prostate cancer

Observations:

Incidence of prostate cancer is higher among pilots, flight attendants, and rotating shift workers than the general population (RR as high as 3.0 in some cases!).

Circadian rhythms of androgens is absent & clock genes are disrupted in prostate cancer; the latter of which is reversible with melatonin which also suppresses prostate cancer progression.

Interestingly, radiation treatment is significantly more effective before 5pm than after.  I don’t know why this is; could be a spurious correlation.  Or not.

 

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Discordant insulin sensitivity on a high protein diet

So, we have another “high protein” weight loss study (Smith et al., 2016).  Or really, a “low (0.8 g/kg) vs. moderate (1.2 g/kg) protein weight loss study.”  In brief, it took ’em about 6 months to lose 10% of their starting body weight, then were given 4 weeks of weight stability before “after” measurements were taken.

Important: this was not a contest to see who would lose more weight; they kept going and adjusting food intake until both groups lost 10%.  Not really ad lib, but otherwise a good study design imo.  The intervention was relatively weak (eg, protein 0.8 vs. 1.2 g/kg), but on the plus side, that’s realistic and very “do-able.”  If you’re interested in super-high protein diets (3-4 g/kg), check out research by Jose Antonio.

 




 

Big yet not unexpected finding: the low protein group lost about twice as much muscle than the normal protein group.

 

fat-free-mass

 

The isocaloric normal protein group lost more fat and less muscle than the low protein group.

But then everyone freaked out because the low protein group experienced a significant improvement in muscle/liver insulin sensitivity whereas the normal protein group didn’t:

 

glucose-rate-of-disappearance

 

-The headlines were hilarious, like, “high protein makes weight loss not work anymore.”

-Then some critics jumped the shark and blamed it on “liquid calories,” because whey protein shakes are totes non-Paleo, and #JERF.

-TBH, I found more interesting the changes in adipose insulin sensitivity

The normal protein group had the most insulin sensitive adipose of all groups… yet they lost more fat mass despite eating just as much or even slightly more than the other groups.

 

adipose-insulin-sensitivity

 

Does this mean they’re doomed to regain the weight?  I don’t think so, as high dietary protein is one of the strongest predictors of weight loss success long-term.

HERESY!  the low protein group had: 1) lower basal insulin than the normal protein group; 2) lower adipose insulin sensitivity; 3) ate less (NS); yet lost less fat mass.

 




 

In other words, the normal protein group had higher basal insulin, more insulin sensitive adipose tissue, and slightly higher food intake (NS).  According to the insulin model, they should’ve lost less fat mass than the low protein group, but they didn’t.

Is this another chink in the armor of the insulin model?

The truth seems to be: people lose weight on both LC and LF diets by giving up junk food.  On LC, this is accomplished by giving up carbs; on LF, this is accomplished by switching to better carbs.  Some people adhere better to one diet or the other.  Maybe insulin sensitivity has something to do with it.

Insulin from high protein: not bad?
Insulin from good carbs: not bad?
Junk food: no bueno.
So maybe just maybe it’s not just ze insulin…

 




 

Back to the protein…

This was not sorcery; it’s been seen before in a variety of different paradigms: dietary protein has a profound impact on nutrient partitioning.

Yes, even when it’s liquid calorie insulinogenic whey protein isolate bro-shakes.

Yes, even when it’s not crazy-high levels of protein…  seriously, 1.2 g/kg is not “high”

 

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Past blog posts on [the non-sorcery of] dietary protein:

Holiday feasts, the freshman 15, and damage control

Dietary protein, ketosis, and appetite control.

Nutrient Partitioning: …a *very* high protein diet.

Protein “requirements,” carbs, and nutrient partitioning

Cyclical ketosis, glycogen depletion, and nutrient partitioning

Meal frequency, intermittent fasting, and dietary protein

Muscle growth sans carbs

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calories proper

 

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Keto myths & facts

:::begin rant:::

Trigger warning?  Maybe.

Disclaimer: I’m pro-LC (P<0.05), but not anti-LF because LF works better than LC for some people.  And with the exception of things like keto for neurological issues, I think macros take a back seat to many other factors.

Myths: carbs cause insulin resistance (IR), diabetes, and metabolic syndrome.  Carbs are intrinsically pathogenic.  If a healthy person eats carbs, eventually they’ll get sick.

And the only prescription is more keto.

cowbell

And of course all of this could’ve been prevented if they keto’d from the get-go.

Proponents of these myths are referring to regular food carbs, not limited to things like Oreo Coolattas (which would be more acceptable, imo).  Taubes, Lustig, Attia, and many others have backed away from their anti-carb positions, yet the new brigade proceeds and has even upped the ante to include starvation.  Because “LC = effortless fasting?”

Does this sound sane?

“No carbs ever,
no food often…
otherwise diabetes.”

oreo-coolatta

no one in their right mind would say lentils & beans cause diabetes

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