Category Archives: depression

Intermittent Fasting and Goalposts

I may come across as harsh on Intermittent Fasting (IF) and I’d like to be clear about something. I’m not saying IF will make you gain body fat or die a slow and painful death. I am saying the quality of evidence presented in human studies suggesting it will benefit you somehow is #weaksauce. Further, I don’t really like the idea of huge refeeds. Like, how can 2000 kcals in one sitting be remotely healthy?

[Patron link]

Metabolic. Mayhem.

 

 

You may have noticed many guru’s sliding away from “intermittent fasting” and “skipping breakfast” and toward promoting a more circadian-appropriate feeding pattern. That’s because it’s about when you eat, not the precise duration of the feeding window.

The studies have been done:

 

Which brings me to the current IF study #weaksauce du jour and it’s implications. But for that you’re gonna have to head on over to Patreon! Five bucks a month gets you access to all articles and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

calories proper

Affiliate links: It’s 2018, join Binance and get some cryptoassets or download Honeyminerand get some Bitcoins for free! And now you can mine Bitcoin from your Chromebook!

Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are 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. I recommend Lion’s Mane for the brain and Reishi for everything else

Join Earn.com with this link.

Start your OWN Patreon campaign!

Share

Global rise of potential health hazards caused by blue light

-induced circadian disruptions in modern aging societies (Hatori et al., 2017)

[Patron link]

While this article could’ve easily addressed the havoc wreaked on most animals (hibernating, migrating, reproducing, etc.) or even many plants by artificial light, the focus is on humans.

Continue reading

Share

Dopamine regulates systemic glucose metabolism in humans

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

Tl;dr: sunlight & breakfast in the morning.

[FULL ARTICLE ON PATREON]

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 PatreonFive bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

Affiliate links: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!

Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off 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

Start your OWN Patreon campaign!

Join Earn.com with this link and get paid to answer questions online.

calories proper

 

 

Cycloset (bromocriptine)

 

 

Go for a walk.

And #eTRF.

 

Share

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)”

[Patron link]

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.

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: It’s 2018, join Binance and get some damn cryptoassets or download Honeyminer and get some Bitcoins for free!

Still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off 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

Start your OWN Patreon campaign!

Join Earn.com with this link and get paid to answer questions online.

calories proper

 

 

It STARTS with Sleep.

 

Share

Circadian rhythms, sleep deprivation, and human performance

“Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep-wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance (Goel et al., 2013).”

[Patron link]

 

 

Acute and chronic sleep restriction degrade neurobehavioral functions, attention, cognitive speed, and memory. Strictly according to the studies (not your n=1), < 5.5 hours is bad, < 7 hours is suboptimal, and ~ 9.5 hours may be optimal. Seems like a lot; who has time to sleep 9.5 hours?!

Above image shows cerebral blood flow (orange) in the same person’s brain during a Psychomotor Vigilance Test performed in the morning and afternoon. Interestingly, most participants perform better in the afternoon and this is associated with more blood going to a different part of the brain.

“Sleep is a ubiquitous biological imperative that appears to be evolutionarily conserved across species.” Mandatory for optimal attention and cognitive performance.

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.

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

calories proper

 

It STARTS with Sleep.

Social jet lag.

Share

Start paying attention to REV-ERB alpha

Hey team, remember when I was making wild predictions about REV-ERB alpha?

[Patron link]

“Food for thought: an endogenous ligand of Rev-erb is heme (the iron-binding element in red blood cells). Heme is degraded into bilirubin.  Elevated levels of bilirubin cause jaundice. A treatment of neonatal jaundice is exposure to blue light. Blue light is a major regulator of circadian rhythms and Rev-erb is an executive-level player in this game. The primary mechanisms of blue light appear unrelated in these two models (melanopsin activation vs. bilirubin photoisomerization), but seem intertwined, because heme activates Rev-erb.  Cool.” (From HERE)

and statements:

“Pharmaceutical-grade circadian augmentation = unwittingly better-timed meals? Improved body composition? …they were eating more and moving less. … One possible mechanistic explanation comes from mice lacking Rev-erb in skeletal muscle (Woldt et al., 2013). Mitochondrial biogenesis was impaired and exercise tolerance was reduced in these mice. Spontaneous physical activity was lower; thus, it stands to reason that Rev-erb agonism may improve skeletal muscle mitochondrial function. This isn’t entirely consistent with the drug study, but pretty close.” (From HERE)

 

REV-ERB is really really good for skeletal muscle.

Beta-hydroxybutyrate inhibits activation of the NLRP3 inflammasome.

 

 

Well, so does REV-ERB alpha! In a new study, knocking down REV-ERB alpha jacked up NLRP3 and pharmacologically enhancing it attenuated NLRP3 (Pourcet et al., 2017). The consequence of this in REV-ERB KO mice injected with LPS was hyper-inflation. No bueno. Mice given the commercially-available REV-ERB alpha agonist “Stenabolic” were protected.

I’m geeking out about REV-ERB alpha & SR9009. And fwiw, I don’t think anything will actually fully replace the benefits from actual physical activity and/or exercise, although it’s very hard for some people; eg, COPD, CHD, etc. In those populations, if they can’t exercise enough to really improve their condition, something like this might help. But I’m sure perfectly healthy people are going to try it. If you do, let us know in the comments!

For more about this fascinating research and how it can work for you (or if you just like what I do and want to support it), head over to Patreon! Five bucks a month gets you full access and there are many other options.

It’s ad-free and you can quit 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.

UPDATED Affiliate links: 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. I recommend Lion’s Mane for the brain and Reishi for everything else

calories proper

Become a Patron!

 

 

 

Regulation of Circadian Behavior and Metabolism by Synthetic Rev-erb Agonists (Solt et al., 2013)

Rev-erb alpha modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy (Woldt et al., 2013)

SERcadian Rhythms

Seriphos

Share

Poor sleep, “dietary disinhibition,” and weight gain

“Dietary disinhibition”

In school, the concept was taught like this: recruit a bunch of people and tell them it’s for a cookie taste-testing project. Give them a form with a bunch of questions about cookie quality (taste, texture, sweetness, etc.) and a plate of cookies.

[Patron link]

SWITCHAROO!

They aren’t there for a cookie taste-test. It turns out that some people experience “dietary disinhibition” wherein if they eat one cookie, they think something like “well, I’ve blown my diet for the day, so might as well just eat the whole plate of cookies” (actually, I’m pretty sure it’s way more complicated than that, but I learned it in a nutrition class, not a psychology class).

It’s not a lot of people — most would just take a bite and fill out the questionnaire — but it’s been replicated in enough settings that it’s probably a real phenomenon.

Continue reading

Share

Artificial light and circadian rhythms: blocking the blues

Check out the above image of the electromagnetic (EM) spectrum. Different biohacking eyewear have different purposes, and it largely depends where on the EM spectrum they act.

If you stare at a computer screen (or iPad, smart phone, etc., etc.) all day, the specialized glasses you may want to look into block out light just south of the visible light wavelengths. These will help with eye strain, headaches, etc. You could use bona fide blue blockers for this, as they block blue and everything south, although it’d be overkill and probably annoying due to visual disturbance. Pixels  and Gunnars are good for this, but they’re not especially great at blocking blue light (with the possible exception of the amber-tinted Gunnars).

Warning: there’s an article floating around on the internet saying it’s useless to block blue light because those computer glasses don’t preserve melatonin secretion. This is a STRAWMAN. Computer glasses aren’t designed to block blue light.
The truth: it’s still important to block blue light at night. If you get eye strain or headaches staring at a computer screen, than computer glasses may be appropriate.

 

 

 

Blocking blue light at night is key for proper melatonin secretion and preservation of circadian rhythms.

Most smart devices emit LED light which has a particular spike in the blue range:

 

If you need to light at night: moonlight or candles > amber or red-tinted bulbs  > low watt incandescent bulb. They should be positioned below eye level as light entering the eyes from above more effectively suppresses melatonin than light from below (with the exception of moonlight LOL) (Glickman et al., 2003).

 

Amber lenses to block blue light and improve sleep: a randomized trial (Burkhart and Phelps, 2009)

 

Wearing blue light-blocking glasses in the evening advances circadian rhythms in the patients with delayed sleep phase disorder: an open-label trial (Esaki et al., 2016)

 

Uvex SkypersGunnarsCarbonshades (probably the most effective blue blockers available) … Solar ShieldsBLUblox (less expensive and pretty cool-looking, too) … Spectra479

 

Spectra479 and Carbonshade are offering a 15% discount with the coupon code LAGAKOS!

 

Circadian misalignment augments markers of insulin resistance and inflammation independently of sleep loss (Leproult et al., 2014)

 

For the rest of this article or if you just want to support the show, head over to Patreon!

Three bucks a month for access to all articles and there are many other options. And it’s ad-free.

If you’re on the fence considering it, try it out, you can cancel at any time! Also, there is a limited number of positions remaining at the $3 level.

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

 

calories proper

 

Become a Patron!

 

 

 

Save

Save

Save

Save

Save

Share

Angiotensin: more than just blood pressure.

Pathologically low blood pressure can lead to shock & death.  Angiotensin II is there to prevent that, but it does much more.  A bit non-sequiter, perhaps.

This is what I call teamwork: low blood pressure detected by kidneys –> secretes renin.  Angiotensinogen (liver) is cleaved by renin to Angiotensin I.  Angiotensin Converting Enzyme (lungs [among other tissues]) cleaves angiotensin I into angiotensin II.

RAAS

Angiotensin II increases blood volume and restores blood pressure.  Good if you’ve lost a ton of blood fighting a wild beast; not good if you’re an overweight pen pusher on potato chips.  ACE inhibitors reduce angiotensin II, lowering blood pressure.  ACE is present in lungs probably because it deactivates bradykinin.  ACE inhibitors prevent this which might contribute to one of their side effects, a persistent dry cough which makes these drugs intolerable for many.  One alternative is angiotensin II receptor 1 blockers, or “ARBs.”


If anyone in pharma reads my blog (doubtful, unless they are monitoring for people to polonium-laced blow-dart), this will be their favorite post because I think ARBs are an interesting class of drugs.

If diet and weight loss are inadequate, telmisartan might be the next best thing to manage hypertension in diabetics:  Telmisartan for the reduction of cardiovascular morbidity and mortality (Verdecchia et al., 2011) –> effective at reducing mortality in patients with diabetes.

Efficacy of RAS blockers on cardiovascular and renal outcomes in NIDDM (Cae & Cooper 2012)  –> reduces morbidity and slows progression of renal disease (both hypertension and diabetes contribute to [irreversible] kidney damage, and frequently occur together, which makes this endpoint particularly relevant).  Hyperglycemia should be managed via diet, of course, and ARBs would need to be tested in people following something other than a Western diet (although said people may not even need treatment in the first place) (just thinking out loud here.  Or typing/whatever.)

But enough about blood pressure (<– boring); on to the more interesting stuff:

It started here: Chronic perfusion of angiotensin II causes cognitive dysfunctions and anxiety in mice (Duchemin et al., 2013)

Then: Candesartan prevents impairment of recall caused by repeated stress in rats (Braszko et al., 2012)

And: Anti-stress and anxiolytic effects of [candesartan] (Saavedra et al., 2005)

[Candesartan] prevents the isolation stress-induced decrease in cortical CRF1 receptor and benzodiazepine binding (Saavedra et al., 2006)

[Candesartan] ameliorates brain inflammation (Benicky et al., 2011)   brain inflammation induced by chronic exposure to artificial lights causes depression-like symptoms (in mice) (probably humans, too)

Finally, a human study: Candesartan and cognitive decline in older patients with hypertension (Saxby et al., 2008)

And then there’s this: Angiotensin receptor blockers for bipolar disorder (de Gois et al., 2013)


No mechanistic stuff because, well, I have no idea how it works.  On one hand, it might seem obvious that stress & anxiety can raise blood pressure, so something that lowers stress & anxiety could lower blood pressure.  Candesartan appears to do both (cause <–> effect?).  There are two unique properties of candesartan to note: 1) it gets into the brain; and 2) it leads to increased levels of angiotensin II (which presumably can’t do much because candesartan blocks the receptor for angiotensin II).  Perhaps angiotensin II targets a different receptor?  ARBs might blunt angiotensin II-induced CRH secretion, leading to anxiolysis, stress-tolerance, and pro-cognitive effects (that speculation was made possible by a thread on Avant Labs’ Forum and a few posts by Jane Plain on CRH [eg, here & here]).

Oh yeah, ARBs also prevent cafeteria diet-induced weight gain, insulin resistance, and ovulatory dysfunction [in rats] (Sagae et al., 2013).  And are sympatholytic like bromocriptine (Kishi & Hirooka 2013).

“The Angiotensin-melatonin axis” (Campos et al., 2013).

just sayin’

calories proper

Share

Circadian disruptions impact behavior and metabolism in a tissue-specific manner.

The control of circadian gene expression is complex, with layer upon layer of suppressors and enhancers, numerous transcription factors, and a lot of interactions.  A gross oversimplification: Clock and Bmal1 are positive regulators of circadian gene expression; Per and Cry are negative (you don’t really need to know any of this).

 

Some pretty cool progress has been made in examining the effects of global and tissue-specific deletion of circadian rhythm-related transcription factors.  Bear with me 🙂

For example, global Bmal1 knockout mice (ie, mice that don’t express Bmal1 anywhere in their whole body.  Zero Bmal1.  Nil.) (Lamia et al., 2008).  These mice are obese, and exhibit impaired glucose tolerance yet improved insulin sensitivity.

Continue reading

Share