Tag Archives: ketosis

Ketones, Cancer, and the NLRP3 Inflammasome

“Check ‘em all. Do the work. There’s no room for cherry-picking here.

LOOK THE GIFT HORSE IN THE MOUTH”

A few years back, researchers discovered the pseudo-ketone beta-hydroxybutyrate suppressed the NLRP3 inflammasome (Youm et al., 2015). NLRP3 is notorious for aggravating gout symptoms, so it was like: “Yay! A potentially clinically relevant use for ketone supps!” (I think there might be other applications as well, but that’s for another blog post).

Ketones, NLRP3, and IL-1b

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It’s thought that NLRP3 is around during active flares, so gout sufferers would stay on their regular meds and take ketone supps as needed – this is important because from what I understand, gout flares really suck, some people get them frequently, and ketone supps aren’t covered by insurance [yet?].

 

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On the impact of diet on circadian phase setting

We’ve seen that meal size and frequency can influence circadian rhythms, but here are some examples of how nutrients can, too.

Circadian phase advance: going to bed earlier, waking up earlier.  Blue blockers at sunset, bright light at sunrise.  Flying east.  Autumn.

Circadian phase delay: staying up late, sleeping in.  Flying west.  Spring.  Using smart phones, tablets, and iPads in bed at night.  Light pollution.

Relative to adolescents, infants and children are circadian phase advanced.  This is part of what is fueling the movement to delay high school start times.  Kids are mentally better prepared to work later in the day.  With early school start times, performance is down in the morning, but they kill it on video games after school.  Delaying start time by an hour won’t totally fix this, but could help.

 

 

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Endurance Performance Doesn’t Decline on a Low Carb Diet

The new study by Zinn and colleagues doesn’t debunk ketoadaptation. And the authors agree!

In brief, it was 5 ~50-year old recreational endurance athletes. They’ve been training a lot for a very long time. In other words, one way to view this study is the opposite of n00b gainz. Experienced exercisers don’t typically make gains in 10 weeks without drastically changing their training program or increasing protein intake – neither of which occurred in this study.

 

 

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Long-term fat adaptation.

Ketoadaptation

More on physical performance and ketoadaptation

A timeline of ketoadaptation.

 

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Scheduled Meals for Circadian Entrainment

Scheduled Meals for Circadian Entrainment

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Conserved lean body mass? O_o

Alternative title: keto isn’t muscle-sparing if you compare it to any remotely sensible control group.

Exhibit A. Resistance training in overweight women on a ketogenic diet conserved lean body mass while reducing body fat (Jabekk et al., 2010)

The exercise intervention was resistance and progressive.  The diet was ketogenic, confirmed by urinary ketones… of note, presence of urinary ketones is a better indicator of ketosis than any information about diet (although they were advised to start at <20g carb/d).

 

 

As per usual, the LC diet was higher in protein… but that wasn’t enough to induce skeletal muscle growth, even when combined with resistance exercise… worded another way, resistance exercise and more protein prevented ketogenic diet-induced muscle loss:

 

 

Neither group was instructed to restrict energy intake, but from the above graph it’s relatively safe to assume the LC diet counteracted exercise-induced hunger.

Confirmed:

 

 

However, exercise-induced hunger isn’t conducive to fattening because the cause is exercise.  I think.

Ketones may spare muscle during starvation, but not in the context of regular people eating a ketogenic diet.  Otherwise, muscle mass would’ve increased in that study relative to the control group.  Confounded by negative energy balance?  Perhaps, but from where I’m standing, the LC diet did almost exactly what we expected: reduced food intake and induced a selective loss of fat mass.  And exercise also performed as expected: increased muscle mass.  In other words, if you want to gain muscle, you need calories, protein, and exercise.  Keto provides no advantages in this context.

 




 

Exhibit B. The effect of weight loss by ketogenic diet on the body composition, performance-related physical fitness factors, and cytokines of Taekwondo athletes (Rhyu and Cho, 2014)

Keto dieters got 33% more protein (40% vs. 30%), and still managed to lose almost twice as much lean mass as non-ketogenic dieters.

 

(figure from Suppversity)

 

The participants were physically active, and thus likely fairly insulin sensitive, so this may be why those assigned to a ketogenic diet lost less body fat…

 




 

Exhibit C. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women (Volek et al., 2004)

And in this study on sedentary insulin resistant folk, keto still wasted muscle (NS) despite more protein and calories:

 

 

If you’ve been paying attention, this wasn’t unexpected.

Sedentary and overweight: more fat loss on keto.

Keto and sedentary: muscle loss.

Sleep well, get your circadian rhythms entrained proper — otherwise these efforts will give you a mere fraction of the benefits.

 




 

Other~

Protein + exercise works: Interactive effects of an isocaloric high-protein diet and resistance exercise on body composition, ghrelin, and metabolic and hormonal parameters in untrained young men: A randomized clinical trial (Kim et al., 2014)

Simply replacing carbs with fat, or resisting food for as long as possible after waking up and staring at your smart phone all night: doesn’t work.

#context

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Cyclical ketogenic diet and carb refeeds

Potential conclusion (pending full texts): “if you’re gonna keto, no need to carb”

I think these three abstracts are all referring to the same studies.  I haven’t seen the full texts.  My takes are in italics, after each abstract.

Exhibit A. The Effects of an Eight Week Ketogenic Diet vs. a Cyclical Ketogenic Diet on Performance and Testosterone in a Resistance Training Program (Lane, Lowery, Volek, D’Agostino, Wilson, et al., 2015)

Introduction: Our lab recently examined the effects of the ketogenic diet (KD) compared to a western diet regarding strength related performance; additionally, free and total testosterone was evaluated. Individuals on the KD saw similar adaptations in strength and similar changes testosterone. Comparisons of the KD against a cyclic (CKD) in strength, endurance, and testosterone have not been previously demonstrated in literature.

Purpose: Therefore the purpose of this study was to investigate the effects of the KD versus a CKD on performance and testosterone in resistance-trained males.

Methods: Sixteen resistance trained males participated in the study (age: 23.5 ± 3.3; weight: 187.6 ± 32.6). Participants on the KD consumed 5% carbohydrate, 25% protein, and 70% fat for 8 weeks. The CKD group applied the same macronutrient ratio to their diet Monday through Friday, while altering the ratio on weekends (50% carbohydrate, 25% protein, 25% fat). A periodized resistance training program was strictly followed 3 days per week throughout the duration of the study with high intensity interval training implemented on intermittent days 2 times per week by all participants. Participants were placed on a 500 kcal deficit derived from basal metabolic rate determined by the Mifflin St. Jeor equation. One repetition maximum (1RM) strength was assessed on deadlift, bench press, and leg press at baseline with a repeat assessment performed Week 8. Strength endurance was assessed on the leg press at baseline and re-assessed at Week 8. Free and total testosterone was evaluated at baseline and at Week 8. An ANOVA with repeated-measures was used to scrutinize the effects of KD and CKD on dependent variables assuming group (KD and CKD) and time (pre and post) as fixed factors. The significance level was set at p ? 0.05.

Results: There were no differences between groups in the performance tests or testosterone levels detected at baseline (p > 0.05). A time effect was observed for bench press and deadlift 1RM (p < 0.01). There was a trend towards a group by time interaction (p = 0.07) which favored an increase in the leg press 1RM in the KD group. There were no significant differences for leg press strength endurance in both groups. For free testosterone, there were no group or group × time interactions (p > 0.05). For total testosterone, there was a group × time interaction following the diet treatment (p < 0.02). The pairwise comparisons revealed that only the cyclic group decreased in total testosterone (10.3%, p < 0.02).

Conclusions: In regards to performance, a strict KD seems to augment positive strength related adaptations when compared to a CKD. These responses may be explained by sustained total testosterone levels seen in the KD group compared to reductions in total testosterone as a result of the fluctuations in macronutrient intake.

Practical Applications: Individuals attempting to optimize adaptations in strength performance while maintaining testosterone levels should perform a KD compared to a CKD.

My take: no difference between KD & CKD, despite testosterone declining in CKD.  This isn’t surprising because small fluctuations within the physiological range are not expected to affect these outcomes.

When protein and calories are controlled, and the #context is a 500 kcal deficit, not really sure what they were expecting.  Because of the constant deficit, insulin will be low even on the carb-up days, and those carbs are more likely to be burned off than replenish glycogen.

 

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Ice age fairy tales

Trigger warning: potentially offensive.

Trying to pinpoint an Ice Age Diet is about as complicated as defining a Paleo or Mediterranean diet… it would’ve been completely different depending on when & where, season, family/tribe, etc., etc.  And while the interwebz are full of anecdotes & guesses (educated & otherwise), there seems to be little reliable information and a lot of contradictions.

And anyway, is this really relevant for us today?

#context

Here’s what I came up with, and why I feel like ranting.

I don’t doubt that humans went through periods of low & high plant consumption, but if someone argues that passing through times of low plant consumption is what “elevated” our species or fostered brain growth or whatever; LOGIC: it can be just as easily argued that passing through times of high plant consumption did the same.  Saying “don’t eat plants because #IceAge” is just as flawed an argument.

Alternatively, considering the importance of #context in our modern environment, couldn’t you also argue that low-plant diets are only evolutionarily appropriate during an ice age (where the Earth is theoretically a giant snow ball LOL)?  Also, if plants are somehow unhealthy, how did we survive periods when hunting was poor?  All of the arguments can go both ways.




I mean, if I lived 10 thousand years ago, I would eat anything I could get my hands on — which would probably look something like a plant-based diet with seafood and whatever else could be hunted, scavenged, etc.  Gotta eat, but why handicap yourself by intentionally avoiding plants – shouldn’t the goal be to spend as little time worrying about this as possible?

If you didn’t have to hunt 24/7, you’d have more time to do other things like acculturation, play, sex, music, story-telling, building traditions, etc., etc.

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Eating in the absence of hunger

Good idea? Bad idea? … a bit of a rant

Some gurus swear by the “only eat when hungry” mantra.  I’m neutral on the issue.  In my opinion, it can work for people who are good planners because if you wait until you’re hungry and haven’t planned or prepared a meal yet, then it might be a while until you finally get to eat.  Maybe you’re an hour from home: unlucky => by the time you start cooking, you’re famished and end up overeating.  So you try to repent by skipping breakfast the following morning but fall into the same trap.  Of course, however, it’s not gonna be like this for everyone.

 

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Protein, ketosis, and lean mass

Most people make a big deal about protein.  I do, too.  Low carb diets aren’t muscle-sparing.  Again.

 

 

Comparison of a Low-Fat Diet to a Low-Carbohydrate Diet on Weight Loss, Body Composition, and Risk Factors for Diabetes and Cardiovascular Disease in Free-Living, Overweight Men and Women (Meckling et al., 2004)

Part 1.  Hunger Free Diet(s)

Focus on what they’re eliminating:

LC diet: “limit intake of breads, pastas, rice, and desserts, eliminating intake of deep-fried foods, dried fruit, candy, sweetened soft drinks, and sugar, and increased consumption of vegetables, lean meats, eggs, and nuts”

LF diet: “eliminate high-fat dairy products and substitute with no-fat or LF alternatives, to increase intake of fruits, vegetables, whole-grain breads, and pastas and to eliminate fried foods, cream sauces, and high-fat/sugar cakes, pastries, chocolate, and candy. They were also asked to reduce use of oil products in cooking. As with LC subjects, LF subjects were encouraged to consume lean meats as alternatives to high-fat meat products.”

 

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Ketones, NLRP3, and IL-1 beta

Interleukin-1 beta: produced by activated M1 macrophages, classical fever-inducing cytokine, mediates cellular inflammation, and induces COX-2 (target of NSAIDs).  Also involved in autoimmunity.  You don’t want none of it but you certainly don’t want a lot of it.

The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasone-mediated inflammatory disease (Youm et al., 2015)

This is a very specific effect: 1) many structurally similar compounds don’t block NLRP3; and 2) beta-hydroxybutyrate doesn’t block activation of other inflammasomes.

 




 

“In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1b secretion in mouse models of NLRP3-mediated diseases such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome and urate crystal-induced peritonitis. Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.”

 

 

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