Tag Archives: ketones

I’m not anti-keto, but I’m not anti-science.

The ketogenic diet inhibits mTOR but spares muscle. Wait, wut?

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mTOR is a key mediator of skeletal muscle growth. Primarily via stimulating protein synthesis, although some researchers are even looking for ways to activate it to prevent atrophy (eg, Dyle et al., 2014) (eg, ursolic acid & tomatidine).

Role of skeletal muscle mTOR in mechanical load-induced growth (Goodman et al., 2011)

Signaling pathways mediating muscle mass in aging skeletal muscle: role of mTOR (Sandri et al., 2013)

Mechanisms regulating skeletal muscle growth and atrophy (Schiaffino et al., 2013)

mTOR is necessary for proper satelite cell activity and skeletal muscle regeneration (Zhang et al., 2015)

 

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Brain Health, Easy Steps

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Tl;dr: sleep, sunlight, seafood, and exercise. Maybe some others. No industrial foods.

Brain-derived neurotrophic factor (BDNF) comes up a lot, so I’ll just tell you now, it’s like brain-fertilizer.

Sunlight promotes dopamine synthesis in your brain (eg, de Lima et al., 2011). Dopamine, via D5 receptor, has a lot of direct effects on memory and learning, but also stimulates BDNF (Perreault et al., 2013). Take a walk outside after breakfast and/or lunch. Bonus: vitamin D is also good for the brain and exercise after meals promotes +nutrient partitioning.

At night, you need melatonin, and for that, you need darkness. In my experience, it’s harder to control sleep onset & duration than time in darkness. T.S. Wiley recommends 9.5 hours of darkness. That’s a lot, I know, but I have a lot of respect for Wiley and she explains it well in Lights Out!

The studies on melatonin supps are mixed (eg, 1, 2, 3, 4) but those on crappy sleep aren’t (eg, 1, 2, 3), so come on fam, at least get some blue blockers (if you choose Carbonshade or Spectra479, use coupon code LAGAKOS for 15% off).

The positive influence of exercise on brain health seems to have many mechanisms, BDNF being one of them (Seifert et al., 2010). Myokines from exercising muscles have a part in this (Philips et al., 2014), so does beta-hydroxybutyrate (eg, Sleiman et al., 2016 and Marosi et al., 2016). Possible role for exogenous bHB supps?

 

 

Niacin boosts BDNF (eg, Fu et al., 2014). Fortunately, it’s fairly abundant in the diet, but if you wanna try something new, nutritional yeast can add cheesy deliciousness to just about anything.

Niacin is also a precursor to NAD+, and this company really REALLY thinks NAD+ is the bomb (see their website for a round-up of the science). Rodent studies have suggested nicotinamide riboside is better at boosting brain NAD+ than niacin (eg, Collins and Chaykin, 1972), but as mentioned above, niacin isn’t hard to find via diet.

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 the rest of this article (which includes advise on foods & supps), or if you just like what I do and want to support it, head over to Patreon! Three bucks a month for access to all content and there are many other options. Sign up soon as the number of spots at the $3 level is limited. It’s ad-free and you can cancel at any time.

 

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

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)

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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 HERETrueDark is running a pretty big sale HEREIf 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. I recommend Lion’s Mane for the brain and Reishi for everything else.

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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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Efficacy of a wide range of things, from sleep & diet to supps & meds, may depend on timing

A study on epilepsy was published comparing gene expression in parts of the brain where seizures developed with adjacent healthy tissue (Li et al., 2017). It was in humans, so they couldn’t really have proper controls, because what healthy person would volunteer to have some of their brain chopped out?

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They found the core circadian rhythm gene CLOCK was reduced in epileptogenic regions of the brain compared to healthy nearby tissue. It could be that this is just the way it is in healthy people, or that the seizure itself reduced CLOCK not vice versa. But the researchers followed-up with animal models lacking CLOCK in either inhibitory or excitatory neurons and showed mice lacking CLOCK in excitatory neurons had a lower seizure threshold and a more severe condition (suggests causation). They had worse seizures in the dark phase, similar to the findings in humans.

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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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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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Long-term fat adaptation.

Ketoadaptation

More on physical performance and ketoadaptation

A timeline of ketoadaptation.

 

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FOOD PROFILE

Hey Fam, announcement: I’m moving to Patreon soon — will still post about 4-5 articles per month with at least 1 open to the public. The rest will be for Patrons. I’m still trying to figure it out and I’m open to suggestions!

 

I loved this – when describing the two study diets, which differed markedly in carb content (10% vs. 53%), the authors said they were similar in energy, protein, and “FOOD PROFILE,” meaning low-processed, lower-glycemic foods.

Non-industrial foods.

Hunger-free Diet(s).

BOOM!

Visceral adiposity and metabolic syndrome after very high-fat and low-fat isocaloric diets: a randomized controlled trial (Veum et al., 2016)

 

What happens when you give up industrial foods and start following a Hunger-free Diet (regardless of carbz)?

 

 

EVERYBODY LOSES WEIGHT

 

 

And le saturated fat? Industrial foods are the problem, not saturated fat. One group went from 48 to 31 grams per day (LFHC), the other group went from 42 to 81 (VLCHF): all metabolic parameters improved in both groups.

 




 

Even their livers shrank:

 

 

My only qualm: everyone lost a bit of muscle. NOT SURPRISING when you cut calories & protein and don’t exercise. Protein dropped by about ~25 grams in both groups. When you cut calories, you need to up protein or start lifting heavy shit otherwise you’ll lose muscle. The ketonez won’t help.

 

 

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

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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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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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