Category Archives: microbiome

Ketosis is a hack: here’s why

There are multiple distinct flavors of diabetes/obesity, as evidenced by the fact that some people have: 1) impaired glucose tolerance (but normal fasting glucose); 2) others have impaired fasting glucose (but normal glucose tolerance); and 3) others have both.  This means there isn’t a linear relationship between these phenomena*.  There are also: 4) obese patients with normal glucose metabolism; and 5) lean patients with type 2 diabetes.

*I think the great Dr. Kraft may have missed some of the nuances here.

There is not 100% overlap among these, suggesting [confirming] distinct diabetes/obesity phenotypes (and probably causes & best treatments).

 

 

midnightsun

 

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Good calories

Nuts are good calories.

I’m not a big fan of the omega-6 fatty acid linoleate, but that’s largely in the context of processed foods and confectioneries, where it’s more than likely no longer in it’s native form (Dc9,1218:2n6)… but in the context of unprocessed whole foods (eg, nuts), a little n6 is fine imo.

What are good calories?  They’re nutrient-dense and don’t generally lead to overeating… like the opposite of soda and junk food.  Nuts are low carb and many are highly ketogenic (eg, Brazils, macadamias, and pecans are ~90%fat).  Mr. Ramsey may even approve of macadamias because they have virtually zero PUFAs.

BONUS: magnesium, copper, selenium, many trace minerals and micronutrients, etc., etc.

I’m not saying you should crack open a can of Deluxe Mixed Nuts and sit down with nothing to do other than NOM NOM NOM ALL THE NUTZ.  I’m talking about a few nuts with a meal.  Possibly earlier in the day (coinciding with LIGHT); nuts are tryptophan-rich and this may improve melatonin onset -> good for circadian rhythms:

nuts and melatonin

Appetitive, dietary, and health effects of almonds consumed with meals or as snacks: a randomized controlled trial (Tan and Mattes, 2013)

In this study, the participants were instructed to eat a serving of almonds (~43g, ~245 kcal) daily for four weeks, at different times of the day (with breakfast, midmorning snack, lunch, or afternoon snack).

Regardless of when the almonds were consumed, the calories were practically completely compensated for.  The participants unwittingly ate less other stuff.  And in 3 out of 4 of the conditions, the almonds were so satiating that the participants actually ended up eating fewer overall calories.

That, in a nutshell, is what I call “good calories,” and I don’t think it’s too far from Taubes’ original definition… especially because it was accompanied with [modest] reductions in body fat (NS).  To be clear, they were instructed to eat more (in the form of almonds), but ended up eating less, BECAUSE ALMONDS.  This wasn’t a cross-sectional study, so no healthy user bias or other obvious confounders.

Further, the participants clearly weren’t obesity resistant.  They were overweight, obese, or lean with a strong family history of type 2 diabetes.  Sam Feltham would’ve been excluded.

This is not an isolated finding: another study showed a dose-dependent response to almonds: 28g or 42g consumed in the morning resulted in a compensatory reduction of hunger and total energy intake at lunch and dinner (Hull et al., 2014).  This wouldn’t happen with soda or junk food.

Another study tested ~350 kcal almonds daily for 10 weeks and concluded: “Ten weeks of daily almond consumption did not cause a change in body weight. This was predominantly due to compensation for the energy contained in the almonds through reduced food intake from other sources” (Hollis and Mattes, 2007).

Almonds vs. complex carbs? Almonds, FTW.

1 Brazil nut daily: “After 6 months, improvements in verbal fluency and constructional praxis (two measures of cognitive performance) were significantly greater on the supplemented group when compared with the control group.”    ONE FRIGGIN’ NUT!

http://www.dreamstime.com/-image11630100

Walnuts protect against alcohol-induced liver damage (in rats) (Bati et al., 2015) and may improve brain health (in humans) (Poulose et al., 2014).

Pistachios improve metabolic and vascular parameters (Kasliwal et al., 2015).

Meta-analysis (not an intervention study): nut consumption is associated with lower risk of all-cause mortality (Grosso et al., 2015). Yeah yeah yeah, I know, correlation =/= causation.  Whatever.

Nuts are good calories.  That’s all I’m saying.

Tl;dr: buy these and one of these, not this.

For personalized health consulting services: drlagakos@gmail.com

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Ketone bodies as signaling metabolites

*non sequiter*

One of the ways dietary carbohydrate contributes to liver fat is via ChREBP: “carbohydrate-response element binding protein.”  It responds to a glucose metabolite and activates transcription of lipogenic genes.  Insulin helps.  Ketones do the opposite (Nakagawa et al., 2013), by inhibiting the translocation of ChREBP into the nucleus where it does it’s dirty work:

 

ChREBP

 

More interestingly, ketones are histone deacetylase inhibitors (HDACi)… this leads to more histone acetylation.  Benefits of fasting sans fasting?  Modulating of acetylation is a MAJOR regulator of circadian rhythmicity.

Butyrate is another HDACi, so have some fibrous plant foods with your red wine and dark chocolate.  Anti-aging (mostly worm studies, but still).

 

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Sweet’n Low

I didn’t want to blog about the artificial sweetener study; to be honest, I didn’t even want to read it.  I just wanted to report: 1) how many Diet Cokes are we talking about; and 2) when are you going to die.

Artificial sweeteners induce glucose intolerance by altering the gut microbiota (Suez et al., 2014)

Non-caloric artificial sweeteners (NAS) = saccharin, sucralose, and aspartame. Saccharin worked the best (worst) in the mouse study, so they tested it in humans.  This was the part I found most relevant: seven healthy volunteers (5 men & 2 women, aged 28-36) who did not typically consume a lot of sweeteners were recruited and given 120 mg saccharin three times per day.  360 mg saccharin is ~10 packets of Sweet’n Low.

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Paleo Plants and Carnivory

From what I gather, it’s been difficult to pinpoint the role of plants in the diet of our ancestors for a variety of reasons.  For example, evidence of plants on cooking tools and dental remains is suggestive but doesn’t disprove the possibility that said evidence came from preparing the plants for some other purpose (eg, tools, weapons, or medicine), or that the stomach contents of an herbivore was ingested (which gets partial credit).

That said, after reviewing a few studies on the topic (see below), it’s safe to say that plants were eaten, probably frequently, and the types & quantities varied seasonally & geographically.  Collectively, the data suggest we aren’t carnivores.

…you had to have something to hold you over until the next fish fell prey to your deadly hunting spear…

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Animal fibre

Fruits and veggies, fermented or otherwise, aren’t the only source of prebiotics in your diet.  Eat a whole sardine and some of the ligaments, tendons, bones, and cartilage will surely escape digestion to reach the distal intestine where they will be fermented by the resident microbes.  

sardines

Salmon skin and the collagen in its flesh, the tendons that hold rib meat to the bone, and maybe even some of the ligaments between chicken bones.  All of these are potential prebiotics or “animal fibres.”  And it may explain why fermented sausages are such good vessels for probiotics.

“Animal prebiotic” may be a more appropriate term because the food matrix is quite different from that of non-digestible plant polysaccharides.  And while I doubt those following carnivorous diets are dining exclusively on steak, these studies suggest it might be particularly important to eat a variety of animal products (as well as greens, nuts, dark chocolate, fermented foods, etc.) in order to optimize gut health.

almonds

These studies are about the prebiotics in a cheetah’s diet.  Cheetah’s are carnivores, and as such, they dine on rabbits, not rabbit food.

cheetah

As somewhat of a proof of concept study, Depauw and colleagues tried fermenting a variety of relatively non-digestible animal parts with cheetah fecal microbes (2012).  Many of the substrates are things that are likely present in our diet (whether we know it or not).

Cartilage

Collagen (tendons, ligaments, skin, cartilage, bones, etc.)

Glucosamine-chondroitin (cartilage)

Glucosamine (chitin from shrimp exoskeleton? exo bars made with cricket flour?)

Rabbit bone, hair, and skin (Chicken McNuggets?)

Depauw ferments

The positive control, fructooligosaccharides (FOS), was clearly the most fermentable substrate; however, glucosamine and chondroitin weren’t too far behind.  Chicken cartilage and collagen were also well above the negative control (cellulose).  Rabbit skin, hair, and bone weren’t particularly good substrates.

As to fermentation products, collagen, glucosamine, and chondroitin were actually on par with FOS in terms of butyrate production:

Depauw SCFAs

Glycosaminoglycans (glucosamine and chondroitin) are found in cartilage and connective tissues (ligaments and tendons) and may have been mediating some of these effects as they’re some of the carbiest parts of animal products.  Duck Dodgers wrote about this in a guest post at FTA and in the comments of Norm Robillard’s article (probably elsewhere, too); very interesting stuff.

The authors also mentioned that the different fermentation rates in the first few hours suggests an adaptive component (some took a while to get going), or that certain substrates induced the proliferation of specific microbes.  “Animal prebiotics.”

Depauw close up

This is particularly noticeable for FOS (solid line), which is a plant fibre that wouldn’t really be present at high levels in a cheetah’s diet, so the microbes necessary to ferment it were probably not very abundant (initially).  Chicken cartilage (long dashes), on the other hand, started immediately rapidly fermenting, perhaps because this is more abundant in the cheetah’s diet.

Depauw took this a step further and fed cheetahs either exclusively beef or whole rabbit for a month (2013). Presumably, the beef had much less animal fibre than whole rabbit.  When they initially examined fecal short chain fatty acids, there were no major differences between the groups:

SCFAs per gram

However, if you take into consideration that the whole rabbit-fed cheetahs produced over 50% more crap than meat-fed cheetahs, then some other differences become apparent.  For example, the concentration of total SCFAs is actually greater in the feces from whole rabbit-fed cheetahs:

updated table

edit: la Frite pointed out that the table in the original manuscript is incorrect; the total SCFA numbers are reversed. The excel table above is corrected.

Further, the mere fact that there was 50% more fecal mass per day pretty much confirms way more animal fibre in whole rabbits.  And while neither of these studies were accompanied by microbial analysis, a more recent study on cheetahs fed primarily meat, “randomly interspersed with unsupplemented whole rabbits,” showed low levels of Bacteroidetes and Bifidobacteria, two potentially health-promoting groups of microbes (Becker et al., 2014).  I suspect this may have been at least partially due to a relative lack of animal fibre, compared to the Depauw’s exclusive whole rabbit diet.

Human digestive physiology and gut microbes are certainly far different from that of a cheetah, but maybe we too receive some prebiotic benefits from these animal fibres… just something to think about next time you’re eating sardines or pork ribs.

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