Category Archives: mortality

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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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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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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Circadian timing with REV-ERB and PERIOD

The circadian proteins Bmal and casein kinase (CK) enhance and degrade Period (PER), respectively, by completely different mechanisms.  Both are necessary, but at different times of day… #context

Gross oversimplification: the Bmal party is kicked off in the morning by LIGHT, and acts to increase PER by night (among many, many other things).  As the day progresses, REV-ERB the Repressor slowly shuts down Bmal, so that peak PER occurs in the evening and doesn’t carry over until the next morning.  GSK3b activates REV-ERB the Repressor.  Lithium puts the system in fast forward, leading to phase advance* and ZZZ’s when timed right, at night… I think

 

Lithium GSK3b image

 

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Circadian Disruption Impairs Survival in the Wild

…just read that huge disasters, ranging from Exxon Valdez to Chernobyl, may have been due, in part, to ignorance of basic principles of circadian rhythms.  Gravitas.

 

circadian rhythms

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Angiotensin: more than just blood pressure.

Pathologically low blood pressure can lead to shock & death.  Angiotensin II is there to prevent that, but it does much more.  A bit non-sequiter, perhaps.

This is what I call teamwork: low blood pressure detected by kidneys –> secretes renin.  Angiotensinogen (liver) is cleaved by renin to Angiotensin I.  Angiotensin Converting Enzyme (lungs [among other tissues]) cleaves angiotensin I into angiotensin II.

RAAS

Angiotensin II increases blood volume and restores blood pressure.  Good if you’ve lost a ton of blood fighting a wild beast; not good if you’re an overweight pen pusher on potato chips.  ACE inhibitors reduce angiotensin II, lowering blood pressure.  ACE is present in lungs probably because it deactivates bradykinin.  ACE inhibitors prevent this which might contribute to one of their side effects, a persistent dry cough which makes these drugs intolerable for many.  One alternative is angiotensin II receptor 1 blockers, or “ARBs.”


If anyone in pharma reads my blog (doubtful, unless they are monitoring for people to polonium-laced blow-dart), this will be their favorite post because I think ARBs are an interesting class of drugs.

If diet and weight loss are inadequate, telmisartan might be the next best thing to manage hypertension in diabetics:  Telmisartan for the reduction of cardiovascular morbidity and mortality (Verdecchia et al., 2011) –> effective at reducing mortality in patients with diabetes.

Efficacy of RAS blockers on cardiovascular and renal outcomes in NIDDM (Cae & Cooper 2012)  –> reduces morbidity and slows progression of renal disease (both hypertension and diabetes contribute to [irreversible] kidney damage, and frequently occur together, which makes this endpoint particularly relevant).  Hyperglycemia should be managed via diet, of course, and ARBs would need to be tested in people following something other than a Western diet (although said people may not even need treatment in the first place) (just thinking out loud here.  Or typing/whatever.)

But enough about blood pressure (<– boring); on to the more interesting stuff:

It started here: Chronic perfusion of angiotensin II causes cognitive dysfunctions and anxiety in mice (Duchemin et al., 2013)

Then: Candesartan prevents impairment of recall caused by repeated stress in rats (Braszko et al., 2012)

And: Anti-stress and anxiolytic effects of [candesartan] (Saavedra et al., 2005)

[Candesartan] prevents the isolation stress-induced decrease in cortical CRF1 receptor and benzodiazepine binding (Saavedra et al., 2006)

[Candesartan] ameliorates brain inflammation (Benicky et al., 2011)   brain inflammation induced by chronic exposure to artificial lights causes depression-like symptoms (in mice) (probably humans, too)

Finally, a human study: Candesartan and cognitive decline in older patients with hypertension (Saxby et al., 2008)

And then there’s this: Angiotensin receptor blockers for bipolar disorder (de Gois et al., 2013)


No mechanistic stuff because, well, I have no idea how it works.  On one hand, it might seem obvious that stress & anxiety can raise blood pressure, so something that lowers stress & anxiety could lower blood pressure.  Candesartan appears to do both (cause <–> effect?).  There are two unique properties of candesartan to note: 1) it gets into the brain; and 2) it leads to increased levels of angiotensin II (which presumably can’t do much because candesartan blocks the receptor for angiotensin II).  Perhaps angiotensin II targets a different receptor?  ARBs might blunt angiotensin II-induced CRH secretion, leading to anxiolysis, stress-tolerance, and pro-cognitive effects (that speculation was made possible by a thread on Avant Labs’ Forum and a few posts by Jane Plain on CRH [eg, here & here]).

Oh yeah, ARBs also prevent cafeteria diet-induced weight gain, insulin resistance, and ovulatory dysfunction [in rats] (Sagae et al., 2013).  And are sympatholytic like bromocriptine (Kishi & Hirooka 2013).

“The Angiotensin-melatonin axis” (Campos et al., 2013).

just sayin’

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Look AHEAD – Nutrition Disinformation 2.0

The day you’ve all been waiting for has finally arrived.  Results from the Look AHEAD study have been published.  When I first wrote about this study (HERE), it had been prematurely halted because the intervention was providing no benefits.  Everybody was in a state of shock and awe because Low Fat didn’t save lives.  But that was before we even had the data.  

Reminder: the “intensive lifestyle intervention” consisted of a Low Fat Diet & exercise.  The results?  Yes, they lost more weight than control, but they also took more Orlistat (of which I’m not a fan, see HERE for why):

orlistat

Orlistat = pharmaceutically enhanced low fat diet. 

Their normal diets were not healthy, but neither was low fat –>

med use

Medication use increased drastically in both groups.  The pundits have gone wild because medication use was lower in the intensive Low Fat group at the end of the study, but this is Nutrition Disinformation 2.0.  Eerily reminiscent of the recent Mediterranean Diet study, the conclusions are the same: keep eating poorly and the need for medications will increase.  You can call it a lot of things, but not “healthy.”  The alternative –>  How to define a “healthy” diet.  Period.


Significant adverse events:SAE

The only thing to reach statistical significance was more fractures in the intensive Low Fat group, but you didn’t read any headlines that said “Low Fat breaks bones.”  Imagine if that happened on low carb [sigh]  The next closest thing to statistical significance was increased amputations in the intensive Low Fat group :/

gem:History of CVD

Translation: if you were healthy at baseline, then you could tolerate a low fat diet.  Otherwise, not so much.  This is exactly what happened in the Women’s Health Initiative.

Ha

needless to say, none of the “possible explanations” they considered were Low fat diet Fail.

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How to define a “healthy” diet. Period.

Whether you’re strictly adhering to a diet or just doing your own thing, if year after year your GP is prescribing more and more medications to stave off morbidity and keep you intact, then the diet you’re following is most likely Fail.  The same is true if your body weight is creeping upward or your quality of life is creeping downward.lunchables

The glaring Fail of all 3 diets in the recent Mediterranean Diet Study for the medications criteria threw up a huge red flag.  As a brief refresher, at baseline and 5 years later, prescription medication usage was as follows:

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Mediterranean Diet Fail – Nutrition Disinformation, Part I.

Do not get your hopes up, do not pass GO!  do not collect $200.  The Mediterranean Diet.  Fail.

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet (Estruch et al., 2013)

This is one of the biggest diet studies we’ve seen in a while, and no doubt it was a very good one.  It very effectively put the Mediterranean Diet to the test.

I felt compelled to write about this study out of fear for the nutrition disinformation that it would likely inspire.  The Mediterranean Diet is associated with all good things, happiness, red wine and olive oil; whereas the Atkins Diet is associated with artery clogging bacon-wrapped hot dogs and a fat guy who died of a heart attack.  Nutrition disinformation.

If you ran a diet study with 3 intervention groups for 5 years, and by the end of the study everybody (in all 3 groups) was on more prescription medications, would you conclude any of the diets were “healthy?”  If so, then we should work on your definition of “healthy.”

Study details: big study, lasted roughly 5 years, and the diet intervention was pristine.  Mediterranean diet plus extra virgin olive oil (EVOO) vs. Mediterranean diet plus nuts vs. low fat control.  They even used biomarkers to confirm olive oil and nut intake (hydroxytyrosol and linoleate, respectively).  Compliance was good.

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Paleotard, meet potatotard, Op. 132

(credit to Dylan and Woo, respectively, for introducing me to those terms)

Empty calories – the potato

While it has a decent amino acid profile, with only 3 grams of protein it’d take a diabetic amount of potatoes to fulfill your daily protein.  By “diabetic,” I mean about a thousand grams of starch.  potatoes are just as glycemic as white bread.

potato

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