Category Archives: insulin

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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Ketogenic diet as a metabolic therapy for mood disorders

Recent findings and current developments: where do we stand today?

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Great “Tl;dr:” figure ->

 

 

 

There is most definitely a multi-level bidirectional relationship between mood disorders and diet/lifestyle habits. Can diet cause or cure mood disorders? Can mood disorders cause you to eat/behave a certain way? Yes, yes, and yes. #Context.

That said, diet interventions present a unique and potentially useful treatment avenue for mood disorders.

Mood disorders are a significant source of mental capital loss with high rates of treatment resistance, in part, because we have no clue about the causes, full influence of their spectrums, or how exactly the effective pharmacotherapies work.

The ketogenic diet: why it should be explored ->

  1. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including glutamate/GABA transmission, monoamine levels, mitochondrial quantity and quality, neurotrophism, oxidative stress, insulin signaling, inflammation, etc., etc…
  2. Benign dietary ketosis is a very exclusive diet, immediately cutting out many of the potentially offensive foods.
  3. Malign dietary ketosis, while still technically ketosis, is full of unhealthy n6- and trans fat-rich oils, insufficient protein and fibre, etc. It’s basically the bacon-wrapped cheese dog version of keto.

Domains of depressive symptomatology of interest: anhedonia, rumination, suicidality, sleep disruption, appetite dysregulation, among others.

In this context, it may be perfectly legitimate to supplement a low carb diet with exogenous ketones or coconut oil.

BDNF BDNF BDNF!

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Study: protein & seafood. They work!

I liked this study for a couple reasons:

Effect of combined use of a low(ish)-carbohydrate, high-protein diet with omega-3 polyunsaturated fatty acid supplementation on glycemic control in newly diagnosed type 2 diabetes: a randomized, double-blind, parallel-controlled trial (Liu et al., 2018)

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There were FOUR groups: 1) high-carb, low protein (HCLP, aka CONtrol group); 2) LCHP; 3) HCLP+n3; and 4) LCHP+n3. So, instead of just taking a group of people, putting them on LCHP+n3 and comparing the results to baseline, they actually controlled for the variables independently.

 

 

All groups were assign 30% fat and the protein was either 17% or 28%. THIS WAS CONFIRMED with serum urea nitrogen and you know how much I like biomarkers! n3 status of the n3 groups were confirmed with plasma n3’s and you know how much I like biomarkers!

Some more details on the study design…

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calories proper

 

“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.

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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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Mutual influence of sleep and circadian clocks on physiology and cognition

“The 24-hour sleep-wake cycle is one of the most prominent outputs of the circadian clock systems (Heyde et al., 2018)”

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Sleep disruption and circadian arrhythmia induce metabolic, cognitive, and immunological impairments. Is it causal? YES.

 

 

Sleep is highly conserved across the animal kingdom, since the dawn of time.

Interesting comparison: unlike hibernation or a coma, sleep is highly reversible. Lots of rebound regulation: lots of wakefulness makes you tired; lots of sleep leads to increased wakefulness.

Studies have shown improved memory performance after naps and extended sleep durations. Imo, you don’t need to go from 6 to 9.5 hours overnight, but keep that “9.5” on your radar.

Diet is easy, just eat like an adult. You can go 10 days without even eating! Try that with sleep. No, don’t try that. Most definitely incompatible with survival. Sleep deprivation impairs cognitive functions.

As a marker of health: cognitive function >>> how many reps you can do at the gym.

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

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calories proper

 

 

It STARTS with Sleep.

 

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.

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calories proper

 

Obligatory glycolytic cells

Some cells lack mitochondria; they need glucose. And they don’t stop working during starvation because #gluconeogenesis.

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Red blood cells, renal medullar cells, and certain cells in the retina. Now do you see why it would be a problem if they stopped working during starvation? Hint: You’d die rather quickly.

Recommended textbook: Stipanuk or Gropper.

 

 

Those cells are unable to use conventional oxidative metabolism like the TCA cycle, ß oxidation of fatty acids, oxidation of ketone bodies and most amino acids, and the electron transport chain are all mitochondrial pathways absent from those cells.

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.

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

calories proper

 

 

Glucose dynamics during prolonged fasts

This is a somewhat complicated level of metabolism. Which tissues are producing what & how much, what are they burning & how much, etc., etc…

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After a few weeks, things begin to level out — we’ll pick it up there. Much of this is from a class I TA’d for in grad school, this book, and all the Cahill studies.

 

 

“The rate of glucose use at this time is around 90-100 g per day [remember, this is starvation, so all of that glucose comes from gluconeogenesis]. Of that, about 40 g is recycled via the Cori and glucose-alanine cycles and the remainder is ‘new’ glucose, ~18 g from glycerol and ~45 g from amino acids.”

Continue reading

Starvation ketosis and “priority” of brain fuels

“Priority” is a funny concept the fields of nutrition, metabolism, etc. For the brain, it is said to be glucose. It’ll use ketones when glucose is low and ketones are really high, like during starvation, but otherwise it’s just glucose. Why is this? One of my mentors had some great insights…

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“It seems that the loss of some energy as ketones in the urine is the price we pay to provide the brain with a suitable fuel. But there are a number of unanswered questions about brain fuel use. Why does the brain not use free fatty acids? The usual answer given is that they are not transported across the blood-brain barrier fast enough to be used as a major fuel and this is probably true. However, why did the brain not develop a suitable transport system, or localized store of glycogen for that matter.”

WHY NOT FATTY ACIDS?

Textbook: Biochemical, Physiological, and Molecular Aspects of Human Nutrition

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

Affiliate links: still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon codeLAGAKOS and Spectra479 is offering 15% off HERE.
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