Tag Archives: insulin

[FULL ARTICLE ON PATREON]

Posted in Advanced nutrition, diabetes, diet, Dietary fat, empty calories, fat, Fructose, Grains, liver, mortality

Tagged body composition, calories proper, carbs, exercise, high fructose corn syrup, insulin, ketogenic, nutrition, obesity

Dopamine regulates systemic glucose metabolism in humans

Posted on June 1, 2018 | Leave a comment

In Four. EPIC. Experiments (ter Horst et al., 2018)

Tl;dr: sunlight & breakfast in the morning.

Dopamine receptors are downregulated in obese patients and are restored in long-term weight loss patients after bariatric surgery. It’s better to get your dopamine hit via sunlight than sugar duh.

This is some amazing science.

Experiment 1. 50-year old dude with severe OCD gets diagnosed with type 2 diabetes and is only able to get his glucose under control with metformin and 226 IU insulin. At 53, his OCD is treated with deep brain stimulation (DBS). His insulin requirements declined to 180 IU. He didn’t lose weight but went off quetiapine, so maybe coincidence because: 1. quetiapine is diabetogenic; and 2. DBS induces dopamine release.

Two-step hyperinsulinemic euglycemic clamp when DBS is turned off and turned on. BOOM! When it’s on, lower fasting insulin, and better insulin-induced suppression of liver glucose output, free fatty acids, & muscle glucose disposal! DBS improved insulin sensitivity in liver, adipose, and skeletal muscle.

For the rest of the discussion on these super-interesting experiments, head over to Patreon! Five bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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Cycloset (bromocriptine)

Go for a walk.

And #eTRF.

Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, clamp, depression, diabetes, Dopamine, melatonin, muscle, nicotine, sex, sleep, Sun, testosterone, vasopressin

Tagged diet, energy balance, insulin, melatonin, muscle

Mutual influence of sleep and circadian clocks on physiology and cognition

Posted on May 1, 2018 | Leave a comment

“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.

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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It STARTS with Sleep.

Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, circadian, depression, diabetes, Dopamine, Energy balance, insulin, Leptin, melatonin, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

Tagged circadian rhythm, insulin, melatonin, mortality, nutrition, Paleo, sleep

Glucose dynamics during prolonged fasts

Posted on March 22, 2018 | Leave a comment

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

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 →

The Biology of Starvation (intro)

Posted in Advanced nutrition, diet, Energy balance, insulin, Ketosis, muscle, Protein

Tagged calories proper, carbs, diet, energy balance, insulin, ketones, muscle, protein

Metabolism of starvation/fasting =/= low carb diet

Posted on March 9, 2018 | Leave a comment

The Biology of Starvation: Renal Gluconeogenesis

One of the major [obvious] differences in metabolism between fasting and low carb dieting is nitrogen metabolism… because you’re eating protein on a low carb diet, not so much while fasting. During fasting/starvation your body tries to downregulate the urea cycle because you can’t really afford to be ‘wasting’ amino acids/protein. I bet you never thought about the muscle-sparing effect of fat-derived fuels like that!

“Glucose production in starvation” is important because you need to make all of it and reduce the use of it.

For the rest of this article and more, head over to Patreon! Five bucks a month for full access and there are many other options.

It’s ad-free and you can cancel if it sucks 🙂

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, RealMushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.

Posted in Advanced nutrition, diet, Energy balance, Exercise, insulin, Ketosis, Protein, strength

Tagged Atkins, calories, calories proper, diet, insulin, ketosis, mortality, muscle, nutrition, protein

Is gluconeogenesis demand-driven? answer: it depends (#context strikes again!)

Posted on January 4, 2018 | Leave a comment

Context #1. The easiest way to explain gluconeogenesis (GNG) is how it relates to starvation. If you’re not eating food, your brain still needs a steady supply of fuel. Mostly glucose at first (ketones come later), but since you’re not eating anything, glucose comes from hepatic GNG (huge potential supply*) or glycogenolysis (limited supply). *One of the precursors for GNG, glycerol, comes from stored fat (which you’ll die of something else before you run out of stored fat bc GNG).

In this case, it is mostly true that GNG is demand-driven.

If you’re interested in this, more HERE.

Context #2. Protein (which also contains GNG precursors) doesn’t acutely increase glucose. But you might think protein does convert to glucose via GNG but protein also induces a splash of insulin which is why blood glucose doesn’t rise. Read this blog post at least up to the awesome Fromentin study: “8% of the blood glucose produced under optimal gluconeogenic conditions came from dietary protein.” But also check out the Conn & Newburgh studies. And Gannon.

This is usually the reason recreational keto dieters say they can be high protein, which either ends up looking like PSMF or it’s probably not very ketogenic (which doesn’t really matter in this #context; protein is restricted in therapeutic ketogenic diets).

#BenignDietaryKetosis #BDK

For the rest of this article (or if you just like what I do and want to support it) head over to Patreon! Full access for a measly five bucks a month and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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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Context #3. the mouse doctor is in 🙂

Context #3b. Chronic high protein.

Context #4. Random thoughts on animal foods.

Posted in Advanced nutrition, diet, epilepsy, gelatin, gluten, insulin, Ketosis, liver, muscle, Protein, strength, TPMC

Tagged body composition, calories proper, carbs, diet, insulin, ketosis, muscle, protein

Intermittent fasting is nothingsauce

Posted on December 18, 2017 | Leave a comment

So Twitter got supermad when I said the human studies on intermittent fasting are not compelling. Not the anecdotes or n=1’s. The actual human studies.
And instead of “not compelling,” I may have said “nothingsauce.”

Hilarity ensued. I was bombarded with
ALL.
THE.
ANECDOTES.

Hey fam, intermittent fasting is totally awesome & a panacea, but the quality of evidence supporting this in humans is quite low (ie, non-existent).
Please don’t hate me for this.

— Bill Lagakos (@CaloriesProper) December 16, 2017

Someone was kind enough to send me all the proof that I was wrong. Here are the 5 non-Varady studies, reviewed.

Tl;dr: as long as you’re not eating like a child, “Eating > not eating. QED.”

Alternate day calorie restriction (ADCR) improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma (Johnson et al., 2006)

Study design: n=10, 8 weeks, NO CONTROL GROUP. Every other day they ate 20% of normal and ad lib the other days. This would’ve been much cooler if they included a 40% caloric restriction and weight maintenance (WM) control groups. The former to see if ADCR was superior to a similar reduction in energy intake and the latter because people behave differently when their being observed (regardless of which group they’re in) (few studies include a WM control group).

Result: body weight declined by 8%. Is that worth having nothing but a snack every other day? How about compared to 40% CR? Nothingsauce?

Oh yeah, uric acid increased and BDNF decreased. So, gout, kidney stones, and cognitive deterioration. Yummy nothingsauce.

The effects of modified alternate-day fasting diet on weight loss and CAD risk factors in overweight and obese women (Eshghinia et al., 2013)

Study design: similar to the above, and also lacking a control group.

Result: BW declined by 7%.

Critique: same. No control group. Would this have been better than CR or anything else? They basically just say “it’s relatively safe;” but it’s not, really… and some forms of intermittent fasting can have harmful side effects.

For the rest of this article (including some LOLZ & facepalming), head over to Patreon! It gets better (or worse, depending on how you look at it): metabolic mayhem, rebound hyperglycemia, some circadian chicanery #eTRF, and much more.

And stay tuned: since BDNF actually declined in the Johnson study, I’m following up with a review of intermittent fasting vs. various aspects of cognition, memory, mood, sleep, etc.

On Patreon, five bucks a month gets you full access. It’s ad-free and you can cancel if it sucks 🙂

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Posted in Advanced nutrition, diet, Energy balance, insulin, Ketosis, muscle, Protein

Tagged body composition, diet, insulin, ketosis, muscle, nutrition, protein

As if we needed another study about breakfast. Or 4.

Posted on November 19, 2017 | 4 comments

Exhibit A. Participants were given ~30 grams of whey, casein, or carbs 30 minutes before bed (Kinsey et al., 2014). [side note: the closer it is to bedtime, the less food is needed to mess up your rhythms. Worded another way, if you’re gonna have a big dinner, the earlier the better]. The following morning, you guessed it, they weren’t hungry for breakfast. And they had higher insulin levels. FFS. Worded another way, light early dinner -> lower insulin and more hungry for breakfast, in the morning.

Light and food in the morning.

Dopamine and breakfast.

Metabolism is gimped at night.

Exhibit B1. Expecting mothers: “Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05)” (Chandler-Laney et al., 2016).

Evening is not the best time to carb… but it’s not just carbs… and it affects infants, too.

Affiliate discounts: if you’re still looking for a pair of hot blue blockers, Carbonshade is offering 15% off with the coupon code LAGAKOS 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 the taste, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS.

For full access to all articles and more (or if you just like what I do and want to support it), head over to Patreon! It’s only three bucks a month and there are many other options. It’s ad-free and you and you can cancel if it sucks 🙂

Sunlight, Meal Timing, and Circadian Rhythms.

we’re talking some serious epigenetics

4 Comments

Posted in Advanced nutrition, chronopharmacology, circadian, diabetes, Dopamine

Tagged circadian rhythm, diabetes, insulin, ketogenic

Yet another study showing low carb doesn’t impair performance +

Posted on November 6, 2017 | 1 comment

and by some metrics, at least in this study, might even improve it.

Ketoadaptation enhances exercise performance and body composition responses to training in endurance athletes (McSwiney et al., 2017)

Advantage of this study over previous ones: 12 weeks. I believe the choice to opt for self-selection over randomization was to improve adherence (which was pretty good for this 12 week-long study). Downside is, well, it’s not randomized. Crossover RCT is best but it’s always a trade-off: sample size, duration, tools, etc., everything has a price. Literally.

Tl;dr: Ketoadaptation doesn’t diminish performance at high intensity even after “draining the tank.”

The study: we aren’t told much about the diets, just high carb vs. ketogenic. And keto group was advised to drink broths for salts, mins, electrolytes, etc.* Speaking of which 🙂 Kettle & Fire is offering 20% off their delish broths/stock HERE.

*I don’t think this qualifies as cheating in this #context.

Before and after the 12-week dietary intervention, a battery of tests were performed: a six second all-out bicycle sprint (SS), immediately followed by a 100 km time trial (TT), immediately followed by a 3-minute sprint (CPT).

These were well-trained, healthy individuals who continued their training throughout the study. This & duration are two important nuances of this study (more on this below).

The biggest finding …*drumroll* … significantly greater fat loss in the keto group and this wasn’t even a weight loss study. They also jacked up protein intake so they didn’t lose muscle mass. Protein declined in the high carb group, but they were able to maintain muscle because carbs increased.

WHERE HAVE WE SEEN THIS BEFORE

HINT: HERE

Whether they knew it or not, this study was designed to test peak power output before (SS) and after (CPT) exhaustively draining the tank (TT). The theory is that ketoadaptation: 1) spares glycogen so there’s some juice left in the tank for the second peak power test, although racing 100 km is pretty tough so there couldn’t have been much juice left in either group; and 2) ketoadaptation relies more on fatty acids at every level of output, as evidenced by the RER figure (below). Fuel usage comes close at high levels of output (both groups rely more heavily on glucose), but ketoadapted is always a little lower (eg, see the right-most point in the figure below). And fat stores are basically limitless whereas glycogen is not. This may or may not have been a factor here.

PEAK PERFORMANCE

I don’t know why the authors reported peak power relative to body weight. I could understand lean mass, maybe, but keto lost a lot of weight via body fat. If peak power remained the same (as has previously been shown), it would [falsely] appear to increase in this study.

For a more nuanced interpretation of this study (which is good, I promise!), head over to Patreon! Five bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

Also, I’m open to suggestions so feel free to leave a comment or email me directly at drlagakos@gmail.com.

Affiliate discounts: if you’re still looking for a pair of hot blue blockers, Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. TrueDark is running a pretty big sale 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.

For the rest of this article and more, head over to Patreon!

1 Comment

Posted in Advanced nutrition, diet, Dietary fat, insulin, Ketosis, muscle, Protein, strength

Tagged Atkins, body composition, carbs, diet, energy balance, energy expenditure, exercise, insulin, ketogenic, ketones, ketosis, nutrition, protein

Ketosis in an evolutionary context

Posted on August 15, 2017 | 104 comments

Humans are unique in their remarkable ability to enter ketosis. They’re also situated near the top of the food chain. Coincidence?

During starvation, humans rapidly enter ketosis; they do this better than king penguins, and bears don’t do it at all.

Starvation ketosis

Humans maintain a high level of functionality during starvation. We can still hunt & plan; some would even argue it’s a more finely tuned state, cognitively. And that’s important, because if we became progressively weaker and slower, chances of acquiring food would rapidly decline.

Perhaps this is why fasting bears just sleep most of the time: no ketones = no bueno..?

Observation: chronic ketosis is relatively rare in nature. This doen’t mean animals evolved a protective mechanism against ketosis.

Animals with a low brain/carcass weight ratio (ie, small brain) don’t need it. Babies and children have a higher brain/carcass weight ratio, so they develop ketosis more rapidly than adults. Is this a harmful process? No, more likely an evolutionary adaptation which supports the brain.

The brain of newborn babies consumes a huge amount of total daily energy, and nearly half comes from ketones. A week or so later, even after the carbohydrate content of breast milk increases, they still don’t get “kicked out of ketosis” (Bourneres et al., 1986). If this were a harmful state, why would Nature have done this? …and all those anecdotes, like babies learn at incredibly rapid rates… coincidence? Maybe they’re myths. Maybe not.

Ketosis in the animal kingdom

Imagine a hibernating bear: huge adipose tissue but small brain fuel requirement relative to body size and total energy expenditure. No ketosis, because brain accounts for less than 5% of total metabolism. In adult humans, this is around 19-23%, and babies are much higher (eg, Cahill and Veech, 2003 & Hayes et al., 2012).