Category Archives: Uncategorized

Regular circadian effects vs. effects of circadian misalignment.

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans (Morris et al., 2015)

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“Glucose tolerance is lower in the evening and at night than in the morning.”

THE FIRST FRIGGIN’ LINE! Come on fam, please stop arguing against this fact. A basic tenet of circadian biology is our preparedness for food intake in the morning. “Skipping breakfast” is not hormetic. It’s CICO and not in a good way. Metabolism is gimped at night, so you end up having to eat less so you’re double-restricted (no breakfast and less food at night).

 

 

The point of this study was two-fold, in my estimation: 1) determine the normal circadian influences on glucose tolerance; and 2) influence of circadian misalignment.

 

When comparing the glycemic response to identical meals ingested after an identical period of fasting, either at 8 AM (subjective morning or “breakfast”) or 8 PM (subjective evening or “dinner”): postprandial glucose was 17% higher (ie, lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; ie, a circadian phase effect).

 

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Intermittent vs. Continuous Energy Restriction: Study vs. Headlines

It started here: Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: A randomized 1-year trial (Sundfor et al., 2018)

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If intermittent fasting (IF) works for you, awesome. If not, don’t worry, you’re not missing out on much. The above study was a year long and showed no difference between IF and plain old just cutting out some junk food. IF group lost 8 kg, regular dieters lost 9 kg.

 

 

“Intermittent and continuous energy restriction resulted in similar weight loss after one year in men and women with obesity.”

In this study, the IF protocol they employed was most similar to 5:2 wherein you eat normally for five days a week and consume minimal food on two non-consecutive days.

“Feeling of hunger may limit long-term adherence to intermittent energy restriction.” [this seems somewhat unwarranted because, well, they made it a whole year which is pretty “long-term,” imo] [although they consistently reported higher feelings of hunger which may be unpleasant]

Backlash to the above tweet was savage lol and a lot of people cited a 2016 study with which I was familiar… that doesn’t really make their case…

HEADLINE vs. STUDY, people

disclaimer: if you’re hell bent on IF, I’m still a little biased toward #eTRF

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LOOK AT THE DATA, PEOPLE.

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GLUCONEOGENESIS

I get asked about this a lot. Gluconeogenesis. The brain uses the equivalent of 120 g glucose/d. During starvation, brain still uses glucose, but less (because ketosis) and a bit differently (less oxidation, more lactate release).

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The brain and the obligatory glycolytic tissues always use at least some glucose.  During starvation, this glucose comes from gluconeogenesis.

The substrates for gluconeogenesis are primarily lactate, pyruvate & alanine, glycerol, propionate, and some amino acids (not leucine or lysine). The relative proportions change depending on #context, eg, the duration since your last meal, diet composition (keto, LF, etc.), etc.

Recommended textbook: Stipanuk or Gropper.

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For more on renal gluconeogenesis, see HERE.

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Breaking: Melanopsin Discovered in Human Adipose Tissue

PRELIMINARY FINDINGS. PRELIMINARY.

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“It is clear that centrally mediated circadian rhythms play an important role in human health and our results provide initial information about how appropriate sunlight exposure to subcutaneous white adipose tissue (scWAT) might act as a peripheral circadian sensor that contributes to metabolic health. In contrast, a lack of sufficient bodily exposure to sunlight may contribute to long-term scWAT dysfunction and the current epidemics of obesity, diabetes and cardiovascular disease.”

WUUUUUT

Melanopsin is the blue light photon receptor in our eyes responsible for relaying sunlight to the SCN to entrain the central pacemaker. Well, a group of scientists accidentally discovered it fat cells:

Subcutaneous white adipose tissue express a light sensitive signaling pathway mediated via a melanopsin/TRPC channel axis (Ondrusova et al., 2017)

Figure “C” takes the cake. Electrophysiology studies show this receptor is highly sensitive to 465 nm blue/green, meaning it’s probably definitely melanopsin.

and guess what it does?

LIPOLYSIS — see Figure “E” above. Activation of melanopsin reduces the size of lipid droplets and lowers leptin. Interestingly, it also reduces adiponectin.

 

 

They also discovered this in mice, who are covered with fur and most of their melanopsin-containing scWAT is on their bellies which would never be exposed to the sun anyway. So….

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20% off some delish stocks and broths from Kettle and Fire HERE

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else

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HAMMER TIME

Breakfast

Sunlight

The power of a good walk

Circadian rhythms: blocking the blues. AND THE GREENS

 

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Metabolism at night

From circadian entrainment to blood glucose management to appetite control to sleep quality:

 

 

We’re really not made to skip breakfast and eat late at night.  Nearly every line of evidence points to this.  And now:

Is the timing of caloric intake associated with variation in diet-induced thermogenesis and in the metabolic pattern? A randomized cross-over study (Bo et al., 2015)

 

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Hypothyroid-like symptoms, energy balance, and diet quality

Symptoms: fatigue, cold-intolerance, hair loss, decreased libido, constipation… sound familiar?

 

thyroid

Hypothyroid-like symptoms occur relatively frequently during times of rapid fat loss, and this may be at least partially dependent on diet quality.  Another component is the fact of being in an energy deficit, but this is difficult to evade on a weight loss diet.

Tl;dr: large energy deficit = hypothyroid-like symptoms.

Food choices and diet quality is important, too.

The negative impact of low calorie diet-induced weight loss on thyroid biology and energy metabolism is well established, but this figure from Agnihothri and colleagues sums it up rather nicely (2014):Agnihothri

Rapid fat loss causes a decline in TSH and T3.

And in this study on long-term calorie restriction (3-15 years), a similar phenomenon occurred (Fontana et al., 2006).  However, TSH was normal (unlike in Agnihothri’s study), possibly because they were not actively losing weight:

Fontana

Fontana diet

Note: calorie restricted diet had adequate protein…  low T3 because they’re weight-reduced and hypoleptinemic, and normal TSH because they’re not actively losing weight.

But then there’s this study, which shows active weight loss does not necessarily cause reduced TSH levels, if the diet is ketogenic (Yancy et al., 2005):

Yancy

Yancy diet

Also, this study showed reduced T3 after 11 days on a ketogenic diet, but it didn’t impact TSH or resting energy expenditure , suggesting no hypothyroid-like symptoms (Bisschop et al., 2001):Bisschop REE

Bisschop TSH

And lastly, from the [notorious] Ebbeling study:

Ebbeling

Low TSH and low T3, but highest energy expenditure in weight-reduced patients on very low-carbohydrate diet.

Summary

Agnihothri: Low calorie diet-induced active weight loss: low T3 and low TSH; probably low energy expenditure and hypothyroid-like symptoms.

Yancy: Ketogenic diet, active weight loss: normal TSH.

Fontana: Weight-reduced, weight-stable (CR): low T3, normal TSH.

Bisschop: Ketogenic diet, weight-stable (11 days): low T3, normal TSH, and normal energy expenditure (indicative of no hypothyroid-like symptoms)

Ebbeling: Very low-carbohydrate diet, weight-stable (4 weeks): low T3, low TSH, normal energy expenditure (indicative of no hypothyroid-like symptoms).

 

In all of the above studies, leptin mirrored body fat.  And all of the old Rosenbaum & Leibel studies showed the reduction in thyroid function after low calorie diet-induced weight loss could be repaired with leptin treatment.  Their 2002 paper had it all (Rosenbaum et al., 2002)… replacing leptin levels to pre-weight loss levels, which required roughly 3 mg/d, completely restored thyroid levels and energy expenditure:

Leibel

Carbohydrate restriction appears to throw a wrench in the gears.

We also know from rodent studies that excess carbohydrates, particularly fructose, can induce leptin resistance.  Perhaps by improving leptin sensitivity, carbohydrate restriction attenuates some of the hypothyroid-like symptoms associated with an energy deficit.  This would explain the findings of Bisschop’s and Ebbeling’s studies, and would be in line with the known impact of carbohydrate restriction on lowering plasma triacylglycerols, and the theorized (and somewhat controversial) association between high triacylglycerols and low leptin sensitivity.

If you’re on a weight loss diet and are experiencing cold intolerance, fatigue, low libido, or any other hypothyroid-like symptoms, consider either upping the calories or lowering the carbs (or this?).

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20% off some delish stocks and broths from Kettle and Fire HERE.

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.

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Can MCTs skirt the need for strict keto?

Part I.  Ketones are made from fat in the liver.  But dietary fat has a lot of places to go and people to see, so it rarely gets to the liver en masse to a degree great enough to stimulate ketosis.  Not so much for medium chain triglycerides (MCTs).  Upon entry (ingestion), MCTs go to the liver and are metabolized to ketones without passing GO or collecting $200… but is this sufficient to reap the benefits of a ketogenic diet?

GourmetBacon

MCTs (C8-10) comprise ~14 of the fat in coconut oil, and 9.2% in dairy.  As such, average MCT intake is low – ~2% of total fat intake [because we eat a lot of vegetable oil and not a lot of coconuts].

Exhibit A.  Weight-loss diet that includes consumption of medium-chain triacylglycerol oil leads to a greater rate of weight and fat mass loss than does olive oil (St-Onge and Bosarge, 2008)

Healthy people assigned to either ~21grams of either MCTs or olive oil (~12% of total calories on a hypocaloric 1650 kcal/d weight loss diet) for 16 weeks:

This.St Onge BW

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Protein bar takedown, part III (or V)

No more pretense or cute backstory; I just like reviewing ingredient profiles of protein bars.  It’s a hobby of mine:
Candy in disguise, Op. 73 (circa April 2012)
Decepticon Promicor (soluble corn fiber), Op. 81 (June 2012)
Candy in disguise II, Op. 87 (July 2012)
Protein bar round-up, take II (September 2012)

See?

This is a review of Netrition’s “highest rated” bars.  Important notes about this category: these are not necessarily “new” protein bars, or even the bars everyone buy (“best sellers”).  They are the bars everyone who votes like the most.  They’re not the healthiest either… but some come close.   Continue reading

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Yo-yo dieting revisited, a thought experiment

If at first you do not succeed, try, try again.  Opus 94.

Yo-yo dieting is “probably” not good, but giving up is worse IMO.  I say “probably” because obesity researchers have empirically tested just about every single weight loss intervention except this one.  Furthermore, you’d be hard pressed to find an obese population who’d agree to undergo an intensive weight loss regimen, only to intentionally regain the weight.  Rinse.  Repeat.  The study would be a nightmare to design from a philosophical perspective, and psychological torture to the volunteers.  But what if they did?  Would they end up with more fat mass?  Less?  Right back to where they began?

Changes in energy expenditure resulting from altered body weight (Leibel, Rosenbaum, and Hirsch, 1995)

Maybe you don’t recognize the study by name, but you have definitely heard about their key finding: weight loss causes a decline in metabolic rate which makes further weight loss or simply maintaining more difficult.  The other finding was that the opposite also occurs: during weight gain, metabolic rate increases to drive weight back down to its starting point.

bollocks

All-in-all this was a great experiment and it has a lot of street cred; nobody including myself has ever had anything really bad to say about it.  In brief, volunteers were fed either: 1) the maximally tolerated amount of self-selected foods (~6500 kcal!) until they gained 10% of their body weight; or 2) 800 kcal of a liquid formula (40% fat, 45% carbs, and 15% protein) until they lost 10% of their body weight.  

When lean subjects gain 10% of their initial body weight, 80.1% of it is fat mass.  In obese subjects, however, only 58% is fat mass.  Thus, obese people gain more muscle and less fat than lean people during weight gain (e.g., the holidays).  After a 10% weight loss, 64% of the weight is fat mass in lean subjects while a whopping 84% is fat mass in obese subjects.  Thus, obese people lose more fat and less muscle than lean people during weight loss (e.g., New Year’s resolutions).

Here goes nothing:
Take a 100 kg (220 pounds) obese person who has 50 kg fat mass (50% body fat) and a 70 kg (154 pounds) lean person with 14 kg fat mass (20% body fat). After 10% weight loss, body weight declines by 10 kg in the obese subject and 7 kg in the lean subject.  83.6% of the weight lost (~8 kg) is fat mass in the obese subject and 63.7% (~4 kg) is fat mass in the lean subject:

After 10% weight regain, body weight increases 9 kg in the obese subject and 6 kg in the lean subject.  60% of the weight gained (5 kg) is fat mass in the obese subject and 80% (5 kg) is fat mass in the lean subject:

Rinse.  Repeat:

Encore!:

By the end of 3 complete yo-yo cycles, the obese person is down 3 kg body weight, but more importantly their fat mass has declined by 9 kg, from 50% to 42% of their body weight (winner!).  The unfortunate lean subject, however, despite being 2 kg lighter, now has an additional 2 kg of fat mass; in other words, they lost weight but got fattier (20% body fat to start out, 23% by the end).

To be clear, this study has never been done.  But Leibel, Rosenbaum, and Hirsch’s data are impeccable so any flaws in this hypothesis don’t stem from there.  The lean subjects in their study were 154 pounds; clearly not a population in dire need of weight loss.  Perhaps yo-yo dieting got a bad rap from skinny people trying to get skinner, who instead got fattier and told everyone else to give up if dieting didn’t work the first time.  I’m not against pharmacotherapy or bariatric surgery for those in whom diet has failed, but saying “I’m not against” it is a far cry from saying “I’m for it.”  Furthermore, given the results from this thought experiment, among other things, I’m definitely saying “try, try again.”

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Non-sequiter nutrition II, a sugar-thought experiment

The average western diet contains about 50 grams of fructose from a variety of sources ranging from beneficial fibrous fruits to the more insidious sugar-sweetened beverages, soda and juice.  50 grams of fructose.   2 1/2 cans of Coca-Cola.

50 grams x 4 kcal/g = 200 kcal

200 kcal / 2,000 kcal = 10%

10% of your calories are provided by fructose

Even the very high end of fructose intake rarely exceeds ~85 grams, which is still < 20%.  My point?   This is nowhere near the 60% used in mouse diet studies.  Disclaimer: I think fructose causes leptin resistance because of data from such studies.  60% fructose is the fructose that causes leptin resistance and increased susceptibility to obesity.  What does this say about “normal” levels of fructose intake?  Toxic doses cause leptin resistance and obesity susceptibility in mice, well, because they’re toxic, and fructose toxicity just so happens to manifest like that (in mice).   60% is toxic.  15 cans of Coca-Cola per day (depending on who’s counting); but is it relevant?

39 grams of sugar, roughly half of which is fructose

In mouse studies, toxic doses are used for practical reasons- it’s cheap.  The animals can be rendered leptin resistant, glucose intolerant, and susceptible to obesity within a few months of feeding this expensive purified synthetic diet.  This probably (probably) takes over 100 times longer in humans simply because it’s nearly impossible for humans to ingest mouse-toxic-levels of fructose.

1. If the dose was based on body weight (like a drug; e.g., mg/kg or mpk):

60% fructose x 12 kcal/d = 7.2 kcal.  Divided by 4 kcal/g = 1.8 grams per day.

1.8 grams for a 40 g mouse = 45 g/kg.  For a 70 kg (154 lb) human = 3,150 grams of fructose or roughly 12,600 kcal.  I.e., 150 cans of soda or about a week’s worth of calories.  In other words, you’d have to eat a hypercaloric fructose-only diet for months.

2. If the dose was based on calories:

60% fructose x 2,000 kcal/d = 300 grams = 15 cans of soda or doughnuts per day.   News flash: that’s gross, but it won’t kill you.

fructose: still not as dangerous as playing in traffic

How about just lowering your lifetime sugar exposure.  39 grams of sugar is worse than 0.01 grams of stevia or sucralose.  Anyone remember “water?”  Even if you believe “a calorie is a calorie,” exclusively, it’s still really hard to burn off 39 grams of sugar.  Try running 2 miles.  Skinny kids might do this automatically after drinking a can of soda or eating a doughnut.  Not most adults.

Don’t play in traffic either.

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