Isocaloric MCT-supplemented ketogenic diet may improve cognition in Alzheimer’s patients

Posted on December 14, 2017 | Leave a comment

Two-thirds of the time, it works half of the time 🙂

Yes, we all pretend to know the mechanism how ketones may improve cognition in MCI/Alzheimer’s, but we don’t. Nobody does.

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-Preferred fuel? kinda meaningless

-Niacin receptor? if so, where are the studies on niacins or even nicotinamide riboside (the latter is kind of unrelated, but should yield some niacin in vivo) (P.S. blog post on NR in the works).

-Epigenetics? Idk. Of those, I’d say probably all contribute somehow.

Ketogenic Diet Retention and Feasibility Trial #KDRAFT (Taylor et al., 2017)

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The power of a good walk.

Posted on December 10, 2017 | Leave a comment

I walk a lot. Usually after meals; sometimes for sunlight & exercise, other times just because it’s a habit and I like doing it. Sometimes even twice a day (eg, after breakfast and lunch).

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But seriously, it’s way healthier than I thought. This has been in-and-out of the news a few times over the years, but I was always like, “duh,” until I finally looked at the numbers. In some cases glucose & insulin excursions are down 20, 30, even 50%! (mostly depending on the distance covered, but also speed) (but mostly distance).

LOL there are like, a million studies titled “breaking up prolonged sitting improves everything” haha

And since the effects are acute, a lot of well-controlled RCTs — the flipside of that is you have to do it every day… my opinion is that total glycemic exposure over the course of your life is an important metric (more on the MOA below); and with the rise of continuous glucose monitoring systems, this will be proven true.

Exhibit A. The biggest intervention (VERY long walks, 5-6 hrs/d), but most profound results (Manohar et al., 2012)

 

 

 

Exhibit B. Prolonged sitting vs. a 30-minute walk vs. 1.5 minutes walking every 30 minutes throughout the day (Peddie et al., 2013). Both of these interventions are very doable, imo.

In this study, the total daily exposure was 49, 47, and 30 mM / 9 h. 90 seconds of walking every 30 minutes cut glucose by almost half. HALF. Insulin also dropped precipitously. If you work a sedentary job, MAKE TIME FOR THIS. EVERY DAY. GO NOW.

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

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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. 

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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Brain health: more easy steps

Posted on December 6, 2017 | Leave a comment

When describing the length of one of his students’ fingers, the great classical guitarist Andres Segovia said “she has more long fingers than anyone else” — he meant longer fingers… English wasn’t his strong suit haha

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Maximize sunlight exposure, minimize artificial light (or at least get some hot blue blockers). Get at least some physical activity. Those are the basics. Moving on…

Tl;dr: Beef heart, calf liver, and maybe some supps 🙂

Coenzyme Q10

Coenzyme Q10 isn’t approved for the treatment of anything, but hear me out.

We have about a gram of CoQ10 in our entire body, concentrated in the mitochondria of highly oxidative tissues (Saini, 2011). It is found at around 60-110 ug/g in heart (eg, Ercan and El, 2011 & Aberg et al., 1992).

 

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Sunlight is anti-cancer: get some

Posted on December 2, 2017 | Leave a comment

Some important points: there is a lot of evidence that low melatonin mediates the carcinogenic effects of circadian arrhythmia. One of the classical observations was that melatonin-depleted blood from women exposed to bright light promoted tumor growth in a model of human breast cancer and rat liver cancer (Blask et al., 2005). This is also the study that elucidated one possible mechanism: tumors take-up the n6-fatty acid linoleic acid and convert it to 13-HODE, which drives proliferation. Melatonin inhibits this (and more).

Free full article on Patreon!

 

 

There are also data in both humans and rodents that bright light exposure during the day protects nighttime melatonin secretion against artificial light-induced suppression (eg, Kozaki et al., 2016).

 

This was confirmed by showing bright daytime light exposure protected sleep quality in people exposed to artificial light at night (Rangtell et al., 2016).

FYI Rodents exposed to light at night are screwed (Blask et al., 2014):

 

 

 

So, daytime light preserves & protects nighttime melatonin secretion. Melatonin-replete blood inhibits tumor growth. And to connect all the dots: daytime light exposure inhibits tumor growth in some pre-clinical models cancer (eg, Dauchy et al., 2015).

 

And for all you Walburgers, melatonin inhibits aerobic glycolysis in tumors  (eg, Hevia et al., 2017 AND Mao et al., 2016)!

This isn’t a free pass for you to use artificial light at night. Ideally, you should use no artificial light at night. Or dim red ones. Or at least rock some hot blue blockers.

Nocturnal light pollution and underexposure to daytime sunlight: complementary mechanisms of circadian disruption and related diseases (Smolensky et al., 2015)

Doxorubicin resistance in breast cancer is driven by light at night-induced disruption of the circadian melatonin signal (Xiang et al., 2015) (same for tamoxifen [Dauchy et al., 2014])

 

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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. 

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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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, Dopamine, melatonin, nicotine, sex, sleep, Sun, testosterone, vasopressin, Vitamin D

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Activate #Nrf2, then optimize: Brussels sprouts

Posted on November 28, 2017 | 2 comments

Hahaha What can’t you do, Nrf2?

Remember The Day Almonds Became Interesting? Namely, “the long series of  unlikely events that must occur in order for the bifidogenic effects of almonds to manifest.” Well, it happened again. Or the opposite.

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I’m not a huge fan of antioxidant supps for a variety of reasons, including but not limited to ATBC and CARET. There are certainly some exceptions to this, although your body can handle itself quite well under most circumstances.

I am, however, a pretty big fan of periodically doing things like activating #Nrf2, because anti-cancer. Advantage is that if there’s nothing going on, Nrf2 is degraded pretty quickly (can’t really say the same about antiox supps). If there is something going one, Nrf2 rallies the troops to swiftly restore balance: pathways pathways pathways -> DEAD CANCER CELLS.

 

IT DOESN’T GET ANY EASIER THAN THIS, FAM

 

One of the major ways Nrf2 gets it done is by inducing the synthesis of endogenous protective compounds like glutathione. Glutathione synthesis requires sulfury stuff, particularly (if it’s available), cysteine. Guess what?

 

 

Sulforaphane activates Nrf2 and breaks down to provide cysteine for glutathione synthesis. WEIRD COINCIDENCE, I KNOW RIGHT?

WHAT CAN ANY REMOTELY REASONABLE PERSON CONCLUDE FROM THIS?

JOIN MY PATREON TO FIND OUT!

 

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. 

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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Ketone supps and physical performance

Posted on November 25, 2017 | 4 comments

We’ve had a couple more studies on the various ketone supps: two esters (D-b-hydroxybutyrate-R 1,2-Butanediol Monoester and R,S-Butanediol Diacetoacetate) and one beta-Hydroxybutyrate sodium and potassium salts (KetoForce). We’ll call them Clarke, Burke, and Stewart so I don’t get Carpal Tunnel Syndrome typing them out each time. Technically, b-hydroxybutyrate isn’t really a ketone, but whatevs.

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“Clarke”

 

“Burke”

 

“Stewart” (this is actually a blend of the sodium “Na” and potassium “K” [not shown] salts)

 

Two studies on Stewart

Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males (O’Malley et al., 2017)

“Ten healthy, recreationally active men.” The participants did a brief warm-up then a 150 km cycling time trial after receiving 24 g Stewart or salt-matched placebo.  Controlling for salt was cool, but Stewart has about as 5 kcal/g, so the placebo could’ve controlled for that somehow, with either fat or carb, or something… (probably wouldn’t have mattered anyway)

Results: blood beta-hydroxybutyrate reached about 1 mM, power output declined 7% and it took the keto group about 45 seconds longer to complete the time trial.

Oral beta-hydroxybutyrate salt fails to improve 4-minute cycling performance following submaximal exercise (Rodger et al., 2017)

“Highly trained cyclists.” Similar study design as McSwiney’s — drain the tank with 90 minutes cycling at 80% max then 4 minute maximal performance test. Same dose as above in 2 divided doses. Same issue with the control group.

Results: blood beta-hydroxybutyrate reached ~0.6 mM and there was a trivial (non-significant) increase in power. This is actually in line with my interpretation of McSwiney regarding the decline in power output before and after draining the tank; ketoadaptation and all that jazz.

 

One study on Burke

Ketone diester ingestion impairs time-trial performance in professional cyclists (Leckey et al., 2017)

“Internationally competitive elite cyclists.” Two doses of 20 g Burke then a 20-minute warm-up followed by a 31 km time-trial. Non-caloric placebo control, whereas Burke is estimated 4.7 kcal/g. They were well-fed and caffeinated.

Results: beta-hydroxybutyrate reached ~1.1 mM, time-trial took 2% longer, and power was reduced 3.7%.

 

One study on Clarke

Nutritional ketosis alters fuel preference and thereby endurance performance in athletes (Cox et al., 2016)

“High performance athletes.” This study was different: one group got a drink that was 40% Clarke and 60% carbs (by calories), the other drink was 100% carbs. Calorie-controlled. They cycled for an hour at 75% max (to drain the tank), then 30-minute time trial.

Results: this is the first one that worked. beta-hydroxybutyrate reached 2-3 mM and they made it 2% further during the time-trial.

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 eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS.

For my interpretation of these studies and an  explanation why I think the different keto supps had different effects (or if you just like what I do and want to support it), 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. 

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

Posted on November 22, 2017 | Leave a comment

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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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.

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Dopamine and breakfast.

Light and food in the morning.

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 🙂

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Sunlight, Meal Timing, and Circadian Rhythms.

we’re talking some serious epigenetics

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

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SERcadian Rhythms

Posted on November 16, 2017 | 2 comments

The amino acid L-serine may be the next melatonin. A new study showed administration of 3 grams ~30 minutes before bedtime advanced melatonin onset dramatically, almost instantly. It didn’t increase the concentration of melatonin, just onset (Yasuo et al., 2017). For a higher concentration, you’d need AM sunlight and PM blue blockers or actual mel supps (preferably the former) (eg, Burke et al., 2013).

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Important and interesting caveat in the L-serine story: it only worked if the participants received bright light in the morning.

 

In the figure below, “day 1” is no AM light and “day 2” is yes AM light. In both the L-serine and placebo groups, there is a phase advance on day 2 because of the AM light treatment. The advance is markedly greater when the participants received 3 grams of L-serine:

 

Using rodent models (which mimicked the human effect almost exactly), GABA-A receptors were implicated.

Interesting for a couple reasons.

 

 

GABAnergic agents like benzo’s and alcohol don’t really put you to sleep; they knock you out, which isn’t proper sleep. This suggests a non-circadian effect of L-serine; however: 1) GABA-A prevents light-induced SCN activation; and 2) serine advanced melatonin onset (specifically only when combined with light in the morning).

Anyone gonna try L-serine?

In you’re interested consultations with me, reach out: drlagakos@gmail.com.

To learn more about this fascinating discovery or if you just like what I do and want to support it, head over to Patreon! Five bucks a month for full 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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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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Two important blog posts which may hint at how this happened: LIGHT timing for circadian entrainment and Melatonin sensitizes the system.

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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, Dopamine, glycine, melatonin, sex, sleep, Sun, vasopressin, Vitamin D

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Funded by Big ‘Shrooma

Posted on November 12, 2017 | Leave a comment

Reishi, the mushroom of longevity.

“The goal is to maintain or improve brain function and physical performance. And not get cancer.”

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‘Shrooms-every-day is part of my long-term anti-cancer plan. It’s not always a lot per serving, but I try to do the whole variety thing as much as possible, whatever’s available.

Maybe it’s one of those ice-age fairy tales fallacies, but cultures around the world have attributed a large number of health benefits to ‘shrooms for literally, thousands of years:

“Ganoderma [reishi] has a very long history in East Asia as a medicinal mushroom dating back to the Chinese materia medica ‘Shen Nung Ben Cao Jing,’ written between 206 BC and 8 AD. It was considered a superior tonic for prolonging life, preventing aging, and boosting qi.”

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