Tag Archives: carbs

Circadian disruptions impact behavior and metabolism in a tissue-specific manner.

The control of circadian gene expression is complex, with layer upon layer of suppressors and enhancers, numerous transcription factors, and a lot of interactions.  A gross oversimplification: Clock and Bmal1 are positive regulators of circadian gene expression; Per and Cry are negative (you don’t really need to know any of this).

 

Some pretty cool progress has been made in examining the effects of global and tissue-specific deletion of circadian rhythm-related transcription factors.  Bear with me 🙂

For example, global Bmal1 knockout mice (ie, mice that don’t express Bmal1 anywhere in their whole body.  Zero Bmal1.  Nil.) (Lamia et al., 2008).  These mice are obese, and exhibit impaired glucose tolerance yet improved insulin sensitivity.

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Does junk food make you lazy?

From Times LIVE: “Does junk food make you lazy?” 

“A diet rich in processed foods and fat – and the extra weight that comes along with it – may actually cause fatigue, a lack of motivation and decreased performance, according to a recent study involving lab rats… excessive consumption of processed and fat-rich foods affects our motivation as well as our overall health.”

(this is categorically false as both diets used in the study being discussed were very low in fat.)

And from Psych Central: “Rat study shows junk food can make you lazy

The theory itself isn’t too far-fetched: a crap diet can cause weight gain and reduced energy expenditure, or a tendency to minimize any kind of physical activity… instead of: “’laziness’ causes obesity.”  And whether or not it’s true, unlike what some would have you believe, this wasn’t the study to prove it.

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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.

Consults are open, contact me if you’re interested: drlagakos@gmail.com

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Insulin, sympathetic nervous system, and nutrient timing.

Insulin secretion is attenuated by sympathetic nervous system activity; eg, via exercise.  Theoretically, exercising after a meal should blunt insulin secretion and I don’t think this will lessen the benefits of exercise, but rather enhance nutrient partitioning.   And this isn’t about the [mythical?] post-workout “anabolic window.”

Sympathetic innervation of pancreas: norepinephrine –> adrenergic receptor activation = decreased insulin secretion & increased lipolysis (Stich et al., 1999):

Stich insulin

Stich CAS

note how quickly catecholamines are cleared upon exercise cessation

Stich NEFA

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Insulin, dietary fat, and calories: context matters!

Jane Plain recently wrote a great article about the relationship between insulin, dietary fat, and calories.  There are a lot of data on this topic, which collectively suggest: context matters! 

For example,

Insulin and ketone responses to ingestion of MCTs and LCTs in man. (Pi-Sunyer et al., 1969)

14 healthy subjects, overnight fasted; dose: 1g/kg.

In brief, MCTs are more insulinogenic than corn oil.  But it’s not a lot of insulin.  Really.  Enough to inhibit lipolysis, perhaps, but that’s not saying much… & certainly not enough to induce hypoglycemia.

Pi-Sunyer MCT Corn oil

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Carbohydrates, calories, appetite, and body weight.

The Optimal Diet, Atkins, South Beach, Paleo, Zone… all have one thing in common: some degree of carbohydrate restriction.

Low, lower, lowest: does it matter?

There are 4 relatively large, randomized ‘diet-induced weight loss’ studies that all reported fairly comprehensive food intake and body composition data. The studies ranged in duration from 24 weeks to one year and included anywhere between 50 and ~300 overweight and obese participants.

In general, participants assigned to the low fat intervention were advised to restrict calories and fat whereas those assigned to low carb were told they could eat as much as they wanted as long as it wasn’t carbs.

Your mileage may vary – but these studies cover a large number of subjects from a wide range of backgrounds, suggesting the results might be applicable across the board.  Conclusion?  the amount of body fat lost was much more strongly associated with the reduction in carbohydrates than calories.  The only modestly surprising aspect was the magnitude… (see the figures below).

The four studies, in chronological order:

Brehm 2003: over the course of 6 months, those who consumed an average of 163 grams of carbohydrate per day lost 8.6 pounds of body weight while those who consumed 97 grams lost 18.7 pounds.

McAuley 2005: 24 weeks; those who ate 171 grams lost 10.3 pounds, while those who ate 133 grams lost 15.2 pounds, and those who ate 107 grams lost 15.6 pounds.

Maki 2007: 36 weeks; those who ate 186 grams lost 5.7 pounds, those who ate 131 grams lost 9.9 pounds.

Gardner 2007: 1 year – those who ate 138 grams lost 10.3 pounds, 181 grams lost 3.5 pounds, 195 grams lost 4.8 pounds, and 197 grams lost 5.7 pounds.

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Ketoacidosis

Nutritional ketosis is a normal, physiological response to carbohydrate and energy restriction.  A ketogenic diet is an effective weight loss strategy for many.  Ketoacidosis, on the other hand, is a pathological condition caused by insulin deficiency.  The common theme is low insulin; however, in ketoacidosis, blood glucose levels are very high.  Ketone levels are elevated in both states, although are 10-20x higher in ketoacidosis (~0.5-2 vs. > 20 mM).  Nutritional ketosis and ketoacidosis should not be confused with one another, and a ketogenic diet doesn’t cause ketoacidosis.

In ketoacidosis, gluconeogenesis occurs at a very high rate and the lack of insulin prevents glucose disposal in peripheral tissues.  Skeletal muscle protein breakdown contributes gluconeogenic substrates, exacerbating the problem.  This can cause blood glucose to reach pathological levels, exceeding 250 mg/dL.

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Gut microbiome & short-chain fatty acids: resistant starch vs. prebiotics

Bifidobacteria undoubtedly like resistant starch (RS).  They bind and hold on tight, an effect mediated by cell surface proteins.  Big thanks to Tim Steele for passing along many of the studies cited here.  One of said studies showed that treatment of bifidobacteria with proteases abolished the RS binding; but even dead critters would bind if their cell surface proteins were intact (Crittenden et al., 2007).  

I suspect fermented foods have this all figured out.  The microbes in sauerkraut are going to be embedded in & all around the cabbage polysaccharides; likely protected from digestive enzymes (to a degree) and holding on tight.

Something similar has been shown for galactooligosaccharides (GOS) (Shoaf et al., 2006).  In this study, GOS, but not a variety of other fibres, inhibited the binding of pathogenic gut microbes to intestinal epithelial cells.

These mechanisms are likely not mutually exclusive, and both seem like they could benefit the host (us).

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Dietary protein, ketosis, and appetite control.

Dietary protein has a purpose, and that purpose is not carbs.”  Nor is it to break ketosis or stall weight loss.  

Drastically increasing protein intake may reduce the degree of ketosis in the context of a large energy surplus, but this is likely due more specifically to the large energy surplus than the protein.  This would explain why Warrior dieters (1 meal meal per day) often report reduced ketones if they eat too much protein.  It’s more likely that the 2000 kcal bolus is exerting it’s anti-ketotic effect by being a large energy surplus, such that anything other than 90% fat would blunt ketosis.  It’s not the proteins… Want proof?  Here’s an n=1 to try: give up Warrior dieting for a few days and try 3 squares.  My bet is that you’ll be able to increase protein intake and still register ketones as high or higher than before.  There are data to support this and reasons why it may not matter (below).

disclaimer: I don’t think “deep ketosis” is necessary to reap the benefits of carbohydrate-restriction.  But if you love high ketone meter readings, then this might be a better strategy to maintain deep ketosis while getting adequate protein. win-win.

if I hear: “oh no, I was kicked out of ketosis!” one more time… 

All of the studies below are confounded one way or another, but so are we humans.

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Implications of the circadian nature of ketones.

Ketosis.  Happens during starvation and also by restricting carbohydrates (and protein, to a lesser degree)… might be important for epilepsy and bipolar disorder, too.

ketogenesis

Ketostix measure urinary acetoacetate (AcAc) and reflect the degree of ketosis in the blood probably about 2-4 hours ago.  Blood ketone meters measure beta-hydroxybutyrate (bHB) right now.  bHB fluctuates to a greater degree, eg, it plummets after a meal whereas AcAc takes longer to decline.  AcAc/bHB is usually around 1, but increases after a meal (Mori et al., 1990):Ketone body ratio

Conversely, when glucose levels decline and fatty acid oxidation increases, liver redox potential drops which reduces AcAc/bHB.

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