Tag Archives: ketosis

The carb/insulin model of obesity was tested again, and it fared better this time.

Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial (Ebbeling et al., 2018)

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This is another NuSi study designed to evaluate certain aspects of the carb/insulin model of obesity. Understanding the design of this study is critical to being able to properly evaluate the results.

Very important:

 

1. All food was provided, all the diets were healthy, and most people complied.

2. This was a very expensive study. They used great methods.

Study design: during the “Run-in diet,” everyone followed the same diet (C/F/P: 45%/30%/25%) at 40% caloric restriction in order to lose about 10% of their initial body weight.

Importantly, insulin sensitivity was assessed and this may have influenced what happened next, in the weight maintenance phase. I used to put a lot of weight on this theory — eg, the top 25% most insulin sensitive people will do better on low fat whereas the bottom 25% insulin sensitive people (the most insulin resistant, ie) will do better on low carb — this theory has fared better or worse depending on which study you look at. In this study, it did pretty well.

 

 

In the end, we had 38 people in the entering into the high carb arm of the weight maintenance phase and 43 on low carb.

Remember, they all lost weight on the same diet. Now they’re being fed enough to maintain body weight (low carb, moderate carb, or high carb) and we’re measuring things.

Really exciting stuff!

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The current state of affairs in nutri-Twitter

Rant.

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1) It’s almost as if you’re either:

a red meat-eating 110% keto-advocate

or

you think red meat and a ketogenic diet is harmful.

 

If you don’t say the diet is magical, the zealots will try to trick you into, or outright accuse you of saying it’s harmful.

Further,

 

2. And the protein/kidney debate re-surfaced again recently. To be clear: no studies have shown direct harmful effects of protein on kidney function. The studies cited by KDOQI are observational and on end-stage renal disease. Not mild kidney disease or slightly impaired renal function. If I had ESRD, I’d rather play it safe and not enroll in one of Jose Antonio’s high protein diet studies (~4.4 g/kg lol).

I’m pro-LC and HP but not anti-LF. Humans have thrived on a wide variety of diets over time regardless of macronutrient composition. Food quality seems more important in this context.

3. If ketones are muscle-sparing, then…

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The Current Status of the Ketogenic Diet in Psychiatry

Here’s when it’s important to measure your ketones (Bostock et al., 2017). Actually, this is one of the cooler aspects of keto: you don’t need to rely on FFQ’s or diet diaries or other unreliable methods to determine adherence. You just measure ketones directly — if they’re there, you’re adhering to the diet. And while this isn’t really important for body recompositioning purposes, it may matter for neuropsychiatric applications where the ketones themselves may be part of the MOA directly.

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Major limitations in the published studies on this: NOT MEASURING KETONES. If keto didn’t work and they didn’t report ketones, it’s hard to know if keto really didn’t work or adherence failure.

One more point before diving into the studies: rigid, strict adherence is very important here. One study showed efficacy in mild cognitive impairment, but adherence worsened with disease severity. In other words, the people who potentially stood to benefit the most were the least able to stick to the diet. This is why I’m open to coconut oil or medium chain triglyceride-supplemented low(ish) carb diets or even ketone supplements.

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“The Big Breakfast Study” !

Chrono-nutrition influence on energy expenditure and body weight (Ruddick-Collins et al., 2018) HT/ Robb Wolf

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“A growing body of evidence highlights the importance of the biological clock as a modulator of energy balance and metabolism. Recent studies in humans have shown that ingested calories are apparently utilized more efficiently in the morning than in the evening and this is manifest through improved weight loss, even under iso-energetic calorie intake.” YES!!!

Book recommendation: Why We Sleep

 

 

People eating 3 square meals a day shouldn’t be ingesting >40% of their calories late at night. <33% prior to sunset is more like it.

“The SCN of the hypothalamus, the ‘master clock,’ is primarily regulated by the light/dark cycles in order to synchronise the body to the light cycle or solar day…” but it also must by sync’d to the peripheral clocks! aka ‘food-entrainable oscillators’ (FEO).

Sure, caffeine and exercise can influence the liver and skeletal muscle clocks, respectively, but for full central & peripheral co-entrainment: FOOD and LIGHT in the morning (exercise and caffeine are optional for this).

Intermittent fasting? Time-restricted feeding? For more on all that, head on over to Patreon! Five bucks a month gets you access to all articles and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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New study: very low carb diets don’t impair high intensity interval training (Cipryan et al., 2018)

Effects of a 4-week very low-carbohydrate diet on high-intensity interval training responses (Cipryan et al., 2018)

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Relevant study design details: 18 young, healthy, moderately-trained males. First, this was a study on exercise performance. Had it been on glucose management in patients with type 2 diabetes or obesity, this is not the population they would have selected. Second, they needed at least a moderately-trained population otherwise both groups would’ve made big n00b gainz which may have out-weighed any differences incurred by ketoadaptation in 4 weeks.

 

 

Third, 4 weeks is a good duration for this kind of study because maximal ketoadaptation occurs in about 3 weeks and doesn’t get stronger thereafter (gains seen beyond 3 weeks are more associated with training effects).

On to the dietary protocols, results, and 2 other relevant new studies… but for that, head on over to Patreon! Five bucks a month gets you full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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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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Watch the Clock, Not the Scale

I’ve been known to say intermittent fasting is #weaksauce because most of the human studies show little or no effect and people frequently report being hungry (yes, even if LCHF). Human studies, not “n=1’s.”

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Well, now we know why. Time-restricted feeding (TRF) only really works when the feeding window is early (eTRF), as demonstrated by the recent Sutton study which showed, miraculously, great benefits achieved sans weight loss. Calories were strictly controlled in that study to prevent weight loss. AND when the participants were on eTRF, they actually reported less hunger in the evening.

 

 

We know from the studies by Jacobs and Hirsh that under ad lib AND isocaloric conditions, people lose more weight eating all their food for breakfast than those eating all their food for dinner.

 

 

That’s cuz metabolism is gimped at night. Lower metabolic rate and greater propensity to store fat.

Melatonin sensitizes the system, preparing it to optimally partition nutrients in the morning.

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“early Time-Restricted Feeding” #eTRF FTW

I feel exonerated!

Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes (Sutton et al., 2018)

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Tl;dr: 8 prediabetic men, 5 week crossover study. When on eTRF, the only rule was basically dinner no later than 3 pm and no snacking thereafter. It was isocaloric because: 1) studies on meal timing and weight loss have been done; and 2) they wanted to test meal timing specifically, not confounded by weight loss.

 

Also, I think the results are due to meal timing, not fasting duration per se, because of the studies by Jacobs & Hirsh. In brief, they tested meal timing with similar fasting durations and showed people who ate one-meal-a-day all at breakfast lost more weight than people who ate one-meal-a-day all at dinner. First they showed this in an ad lib context and then again in an isocaloric context. Metabolism is gimped at night.

For a discussion of these exciting new data, head over to Patreon! Five bucks a month for access to all articles and there are many other options.

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

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calories proper

 

 

 

 

#eTRF

 

The neuroprotective properties of ketone bodies.

There is some overlap between the metabolic effects of calorie restriction (CR) and ketogenic diets (Maalouf et al., 2009). A lot of the underlying mechanisms are related to mitochondrial quality and quantity, anti-apoptotic factors, and neurotrophic factors (eg, BDNF induced by ketosis).

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The influence of ketones on intermediary metabolism

Two studies: one on infusion of D-b-hydroxybutyrate at three different level producing up to 2 mM at the highest level (Mikkelsen et al., 2014); and one on ingestion of a ketone monoester (R-3-hydroxybutyl-R-3-hydroxybutyrate) producing ~3.2 mM (Myette et al., 2018). Both studies were relatively small (n = 6 and 20, respectively) yet interesting.

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Mikkelsen: mainly justified the use of exogenous ketones in T2DM because of their ability to suppress hyperglycemia and hyperlipidemia. And justified ’em in CNS disorders because adherence is poor in this population and goes downhill with increasing disease severity. They’re anti-ketone salts because: 1) the GI distress and salt load with doses required to get into the 2-3 mM range; and 2) they’re often racemic mixtures of D- and L-b-hydroxybutyrate (“D” is the endogenous one).

 

 

As expected, increasing the infusion dose linearly increased plasma bHB:

Further, as expected, brain uptake increased in parallel to plasma levels:

Interestingly, muscle uptake seemed to become saturated and not increase much further… this may be related to the “muscle-sparing effect of fat-derived fuels,” in other words, muscle is sparing ketones for the brain like it does during late starvation.

For the rest of this article (it doesnt suck, I promise!), head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

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calories proper

ketones inhibit lipolysis

 

 

 

The Fates of Pyruvate

As mentioned in the previous blog, obligatory glycolytic cells lack the apparatus (eg, mitochondria) to fully oxidize fuels down to CO2 and water. Thus, they can’t run on fatty acids, ketones, or beta-hydroxybutyrate. During prolonged starvation, there’s always some glucose in the blood, so they survive.

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Recommended textbook: Stipanuk or Gropper.

Glucose -> glycolysis -> pyruvate: then to lactate or the mitochondria, depending on the context. Skeletal muscle has mitochondria, but if you’re exercising hard, glycogen to lactate produces more energy faster than glycogen to pyruvate to mitochondria. Blood lactate increases in this context. During prolonged starvation, lactate is a valuable precursor for gluconeogenesis, so many tissues release lactate instead of oxidizing pyruvate.

To get the rest of this article (it doesn’t suck, I promise) or if you just like what I do and want to support it, head over to Patreon! Five bucks a month and there are many other options. It’s ad-free and you can cancel any time.

Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

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If you have no idea what I’m talking about, read this then this.

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. recommend Lion’s Mane for the brain and Reishi for everything else.

calories proper