4019 replies to this topic

[lostfalco]

Time Saving Summary for You:

1. Do hex bar deadlifts to produce and release anaerobic myokines into the blood which travel to the brain and enhance cognition. 

2. Hex Bar that I use at home: https://www.lostfalco.com/devices/

 

Discussion:

One of the things that really drove home the importance of working out to me was learning that muscles are actually endocrine organs. 

 

What does this mean?

 

This means that in response to aerobic and anaerobic exercise your muscles:

1) produce more of certain substances AND

2) release more of those substances into your bloodstream.

 

Scientists have dubbed these substances 'myokines'. 

 

Myokines travel throughout your body and impact various organs; including your brain. 

 

Which substances are we talking about here?

 

Aerobic: apelin, BIBA, IL-15, IL-6, irisin, SDF-1, sestrin, SPARC, VEGF-A

https://www.ncbi.nlm...les/PMC7712334/

https://www.ncbi.nlm...les/PMC8829997/

 

Anaerobic: BMP-7, decorin, IGF-1, IL-15, IL-6, irisin, VEGF-A

https://www.ncbi.nlm...les/PMC7712334/

https://www.ncbi.nlm...les/PMC8829997/

 

Here's a nice little pictorial summary...

 

 

As you can see, there is some overlap on what is increased by each form of exercise but the substances are not identical. 

 

It is currently supposed that irisin/BDNF signaling is the big hitter here but this is still very much an area of active research. 

 

Bottom line is, the current research indicates that we should do both aerobic AND anaerobic exercise to maximally enhance brain function.

 

Are any substances decreased?

 

Yep. 

 

Both aerobic and anaerobic exercise inhibit myostatin. 

https://www.ncbi.nlm...les/PMC7712334/

 

If you inhibit myostatin enough you can look like this...

 

 

That mofo is jacked!

 

I first learned about myostatin inhibition in selectively bred Belgian Blue cattle from Richard Dawkins.

 

On a side note: 'The Selfish Gene' is still a fantastic read 45 years later even if evolutionary theory has come a long way since then and Dawkins' discussion of middle world (see vid below at then end of the post) still impacts my thinking on how to frame my views of the universe in terms of 'the smallest things', 'the largest things' and 'the middle things'. 

 

Check out 'The Selfish Gene' here: https://www.lostfalco.com/books/

 

Back to the story at hand....my reasoning is that I can optimize anaerobic myokine release with the least time and effort by focusing on the biggest muscle groups. 

 

The two biggest muscles are the quads and the glutes.

 

One of the best exercises for quads and glutes is the deadlift. 

 

The safest form of deadlift (that helps you align your center of mass with the weight in order to protect your back) is hex bar deadlifts.

 

Voila!! Do hex bar deadlifts to safely maximize anaerobic myokine release.

 

Here's the hex bar I have: https://www.lostfalco.com/devices/

 

I bought rubber 45lb and 35lb plates from a local fitness shop near me. 

 

Enjoy getting jacked muscles and jacked synapses!

 

 

 

 

 

 

Edited by lostfalco, 25 October 2022 - 04:39 AM.

[APBT]

lostfalco, for the purpose of increasing butyrate via the gut microbiome, how much dextrin (Benefiber) do you consume daily? 

 

Is this taken at one time or dosed throughout the day? 

 

Is it taken with or without food or does it matter?

[lostfalco]

lostfalco, for the purpose of increasing butyrate via the gut microbiome, how much dextrin (Benefiber) do you consume daily? 

 

Is this taken at one time or dosed throughout the day? 

 

Is it taken with or without food or does it matter?

Good questions APBT! I'm really glad you asked about dextrin since it is possibly one of the easiest and most powerful brain enhancing substances that only 5% of the U.S. population gets enough of. https://www.vox.com/...iet-weight-loss

 

For those wanting to try dextrin, I've linked to the Benefiber APBT is asking about here: https://www.lostfalco.com/supplements/

 

On to the questions...this is going to be fun!

 

Right now I'm taking 10 grams of dextrin at each of my three meals (it mixes extremely well in water and is virtually tasteless) for a number of reasons:

 

1. 10g x 3 meals = 30g which is the low end of the daily recommended fiber intake (30 - 38g) for adult males. I get more fiber than just 30 grams since I get quite a bit from my food (fiber is one of the most important things we can possibly eat!) but this gives me a nice baseline to work from. Feel free to adjust this according to your own current fiber intake. Also, make sure you start slowly if you haven't taken it before. It will cause stomach rumbling and gas at first (that is your microbiome remodeling itself...which happens immediately upon your first dose in the scientific literature). I'd recommend 1 tablespoon (5 to 6 g) at dinner (so you won't be gassy at work) to start with. See how you respond and go from there. If there is too much gas or bloating, then pull back. If you're fine then feel free the following day to try 1 tablespoon at lunch and 1 tablespoon at dinner. If you're still good, then the day after that take 1 tablespoon at breakfast, 1 at lunch, and 1 at dinner. Keep increasing from there.You get the idea. Some people increase slowly over a couple of weeks but I like to move quickly. Definitely pay attention to your body's unique reaction and pull back or push forward accordingly.

https://www.mayoclin...ds/art-20050948

 

2. I recommend taking it with food at each meal (I take a few big sips of it before I eat anything and I drink it throughout my meal) for two very important reasons:

       A. the production of butyrate and subsequent release of GLP-1 induce satiety which will cause you to eat less

       B. the microbiome has a circadian rhythm that synchronizes with our body's own circadian rhythm and regulates feeding.

 

That last point is too damn cool to not talk about! Please indulge me as I explain...

 

Our circadian clock is entrained to two main external cues: light and food.

 

These cues cause, "daily oscillations of clock gene expression (e.g. Period1/2, Clock, Bmal1, Cry1, and Rev-erbα) in cells both in the brain and in the peripheral tissues". https://www.nature.c...598-018-19836-7

 

Clock genes are expressed in virtually every cell in the body. 

https://www.scienced...550413121001224

 

However, not only does our body sync to light/dark, fed/unfed signals...so does our microbiome!

 

In fact, "The microbiome has circadian rhythmicity and helps the host circadian clock function." 

https://www.nature.c...598-018-19836-7

 

Here's a visual summary:

 

 

The most fundamental clock is the Central Circadian Clock in the suprachiasmatic nucleus (SCN) of the hypothalamus which is entrained by light dark cycles in the environment and especially by blue (480nm) light stimulating the intrinsically photosensitive retinal ganglion cells in your eyes. 

https://www.ncbi.nlm...les/PMC7065627/

 

Here's what the intrinsically photosensitive retinal ganglion cells look like...

 

 

 

 

 

Here is the path from the intrinsically photosensitive retinal ganglion cells of the eye into the suprachiasmatic nucleus of the brain. 

 

 

 

I use the blue light device linked here first thing in the morning to entrain my central circadian clock: https://www.lostfalco.com/devices/

 

Light is the master clock, "whose rhythmic activity determines the time of food intake," and which sets the timing of sleep and physical activity.

 

Once the light sets the feeding rhythm, the feeding then entrains the peripheral circadian clocks and also causes the microbiome to release metabolites which cause rhythmic transcription in the host. 

 

Some of the primary communicators between the microbiome and the host are the microbiome produced short chain fatty acids (SCFAs): acetate, propionate, and butyrate (ie. "High fibre diets enhanced refeeding-induced peripheral clock entrainment.").

https://www.nature.c...598-018-19836-7

 

One of the best fibers for increasing all three of the SCFAs is Benefiber/dextrin. https://www.ncbi.nlm...les/PMC6060387/

 

IF greater synchronization between the host, the environment, and the microbiome...THEN improved health, cognition, and mood.

 

So, let's get to the main takeaways, shall we?

 

Main Takeaways:

1. Go to bed at the same time every night...even on weekends! Of course, there is some flexibility here, but try your best. Set the temperature to between 60 to 67 degrees Fahrenheit (15.6 to 19.4 degrees Celsius) to signal your body that it's time to sleep. Set a 'go to bed' alarm on your phone for the time when you want to go to sleep. Go to bed when the alarm goes off. 

2. Set your 'Central Circadian Clock': Wake up at the same time (or at least as close as you can) every morning. Go outside into the natural sunlight or use a blue light device to set your master central circadian clock first thing in the morning: https://www.lostfalco.com/devices/

3. Sync your 'Peripheral Circadian Clock' AND your 'Microbiome Circadian Clock': Eat meals at the same time (ya know, as reasonably as you can) every day. Use fiber/dextrin at each meal to sync your microbiome's rhythm with your own body's peripheral circadian rhythm. https://www.lostfalco.com/supplements/

4. Remember that we ARE bacteria that ate another bacteria (endosymbiosis) that is filled with bacteria (our gut microbiome) and that is covered in bacteria (skin microbiome). Take care of your microbiome and it will take care of you! After all, microbes were here 4 BILLION years before us and I, for one, welcome our microscopic overlords. See 'Microcosmos' by Lynn Margulis for a fascinating discussion of one of the greatest scientific discoveries of the past century: endosymbiosis (ie. mitochondria were once free living prokaryotes swallowed by another prokaryote to become the first eukaryote). https://www.lostfalco.com/books/

 

Bonus: For more on the essential importance of sleep for proper brain function check out this brief video on the glymphatic system. You'll never want to skip out on sleep again!

 

 

 

Bonus 2: Check out this video for more on clock genes and how they are master regulators of human metabolism in every cell of our bodies.

 

Edited by lostfalco, 26 October 2022 - 08:38 PM.

[lostfalco]

My post got a little long yesterday so I figured I'd put the key takeaways here so they'd be clear on their own. 

 

And, since we are talking about how TIME affects ENERGY (ie. light/food timing affect clock genes affect metabolism (ie. mitochondria) in EVERY cell of your body!), I figured it was worth repeating.

 

So, without further ado...

 

Sync your 'Central Circadian Clock' with your 'Peripheral Circadian Clock' with your 'Microbiome Circadian Clock' by doing the following:

 

1. Set your master 'Central Circadian Clock' (this is in the running for THE most fundamental enhancement currently known to science!): Wake up at the same time every morning AND stimulate your eyes with blue light. Go outside into the natural sunlight or use a blue light device to set your master central circadian clock first thing in the morning after waking. This syncs up energy production in EVERY cell of your body (ie. gets every mitochondria in every cell of your body working together). Take advantage of this enhancement now. Click here for the blue light device I use: https://www.lostfalco.com/devices/

 

2. Sync your 'Peripheral Circadian Clock': Eat your meals at the same time every day to sync your peripheral clock.

 

3. Sync your 'Microbiome Circadian Clock': Take 10g of fiber/dextrin at each meal to sync your microbiome's rhythm with your own body's peripheral circadian rhythm. Click here for the dextrin supplement I use:  https://www.lostfalco.com/supplements/

 

4. Go to bed at the same time every night...even on weekends. Avoid blue light late in the evening and set the temperature to between 60 to 67 degrees Fahrenheit (15.6 to 19.4 degrees Celsius) to signal your body that it's time to sleep. Set a 'go to bed' alarm on your phone for the time when you want to go to sleep. Go to bed when the alarm goes off. 

 

The basis for these ideas (I'll talk about a lot more related ideas in the future) comes from two EXTREMELY active areas of current study:

1. chronobiology https://www.ncbi.nlm...les/PMC7856659/

2. chrononutrition https://onlinelibrar....1111/jnc.15246

 

Check out the two review studies linked above for more info on these exciting new disciplines.

 

Remember, the purpose of these ideas is for you to take the tiny suggestions listed above, act on them, and 'continue to act' on them if they work for you. 

 

It's not about 'doing once', it's about 'doing repeatedly'. 

 

Use the ratchet effect to lock in tiny one-step improvements so that you can incrementally continue up the staircase from a slightly higher step at each iteration. Physicist turned biologist Peter Hoffman talks about how this is a fundamental principle biology itself uses here: https://www.lostfalco.com/books/

 

One of the best ways I've found to lock in improvements is by using the free spaced repetition flashcard app Anki. https://apps.ankiweb.net/

 

Using Anki to remind myself of these ideas EVERY day really helps me 'continue to act' on them over time. 

 

Create simple, 'one idea' flashcards (I call them elemental flashcards) of some of the ideas listed above and study them daily using Anki's built in spaced repetition algorithm. 

 

Even better, use Spaced Generation Learning to build a reference frame to model:

1. photonic (480nm blue light) input into the eye subsequently activating the suprachiasmatic nucleus;

2. dietary input into the mouth (10g of dextrin per meal) affecting clock genes and the microbiome;

3. lack of photonic input in the evening and during sleep AND;

4. lack of dietary input outside your feeding periods.

 

Remember...for EVERY particle there is an antiparticle. For every positive charge there is a negative charge. For every 'input' there is a 'not-input'.

 

The 'lack of a thing' is just as important as 'having the thing'.

 

The lack of photons is just as important as the photons.

 

Time fasting is just as important as time feasting.

 

With these ideas in mind, answer your flashcards by 'drawing your reference frame by hand out loud on a spaced repetition schedule'. 

 

The act of generating speech and generating your reference frame drawing by hand will massively enhance your memory and understanding of the concepts as you generate the answer to your flashcards. 

 

Your better understanding will cause better actions. 

 

Your better actions will cause a better life.

 

I hope these ideas help you get incrementally closer to the life you've always wanted!

Edited by lostfalco, 05 November 2022 - 01:32 AM.

[lostfalco]

Quick Summary to Save You Time:

Eat your first meal early in the day (6am to 8am-ish) and restrict your eating to a 4 to 10 hour window while fasting the rest of the day/night. 

 

Discussion:

I hope everyone is doing great this evening!

 

In my last post, I talked about optimizing time (since I'm obsessed with optimizing spacetime) by getting blue light first thing in the morning (that's the most important one...do it!), eating at the same time every day, taking 10g of dextrin with each meal, going to bed at the same time every night, and embedding these habits into long term memory using Spaced Generation Learning (a time-based learning and memory system).

 

Since we are on the topic of optimizing spacetime I thought I'd discuss a somewhat recent (2022) study that came out comparing two Time Restricted Feeding (TRF) protocols in healthy humans: one that starts early in the day around 6am and another that starts around 11am.  https://www.nature.c...467-022-28662-5

 

Time Restricted Feeding or TRF refers to restricting your food intake to a 4 to 10 hour window each day and fasting the rest of the day. 

 

In dozens of peer reviewed studies this has been shown to:

1. reduce body mass;

2. prevent obesity;

3. improve insulin sensitivity;

4. reduce fatty liver;

5. lower inflammation;

6. reduce blood pressure, etc.

 

The current study compared eTRF with mTRF:

 

eTRF = early Time Restricted Feeding = eat during an 8 hour window within the 9 hour window from 6am to 3pm (ie. if your first bite of food for the day is at 6am, have your last bite by 2pm; if your first bite of food for the day is at 7am, have your last bite of food by 3pm)

 

mTRF = mid-day Time Restricted Feeding = eat during an 8 hour window within the 9 hour window from 11am to 8pm

 

To make a long story short...

 

The 5-week study showed that compared to mTRF and the control group, eTRF:

1. improved insulin sensitivity

2. lowered fasting plasma glucose

3. lowered body mass and adiposity

4. lowered inflammation, and

5. improved microbiota diversity

 

This is only one study (and I'll talk more about TRF soon), but the take home is that it's worth an experiment to restrict your eating to a limited time window (4 to 10 hours) and have your first meal earlier (6am-ish) in the day rather than later in the day (11am-ish). 

 

Have a great (early) dinner!

 

Falco Out.

 

P.s. Seal these ideas in by reviewing them daily! Go to Anki (it's free!) and create simple flashcards now! https://apps.ankiweb.net/

 

#DO.THE.BASICS.

#ALWAYS.INCREMENT.

 

Blue Light: https://www.lostfalco.com/devices/

Dextrin: https://www.lostfalco.com/supplements/

Endosymbiosis (Microcosmos): https://www.lostfalco.com/books/

Edited by lostfalco, 28 October 2022 - 02:39 PM.

[lostfalco]

Quick Summary to Save You Time

Temporal Food Order Dramatically Enhances Bioenergetic Response to Meals: Eat Fiber/Veggies first, THEN Protein, THEN Carbs to control post-meal glucose AND insulin to help you feel your best. (Note: fat can be included with veggies (ie. olive oil dressing, for example) and/or protein (ie. fatty fish, for example).

 

Remember, action is power. Act on this at your next meal! There is no need to change anything else to get positive results. Simply eat fiber(10g dextrin)/veggies, then protein, then carbs, then feel amazing.

 

Read on to see the evidence from healthy human studies!

 

Discussion

We recently discussed:

1. Central Clock Entrainment: Get 480nm blue light first thing in the morning at the same time every morning and go to bed at the same time every night seven days per week. (This is the most important enhancement currently known to science!)

2. Peripheral Clock Entrainment: Eat meals at the same time every day. Eat breakfast (it really is the most important meal of the day in the scientific literature) early and have an eating window between 4 and 12 hours long (ie. 'not-eating' is just as important as eating).

3. Microbiome Clock Entrainment: Take 10g of dextrin at each meal.

4. Spaced Generation Learning: Use this cutting edge memory technique to imprint these ideas into to your long term memory by generating flashcard answers daily. More precisely...predict the future by modeling the past by daily generating answers to flashcards on a spaced repetition schedule by generating spatio-temporal reference frames by hand drawing while speaking your logic out loud. (haha Eloquent. lol)

 

My goal for all of these enhancements is to feel my best throughout every 24 hour period by using light to optimize time to sync up every mitochondrion in every cell of my body with every microbe in my microbiome. (Note: mitochondria actually communicate with each other (and with the nucleus of the cell) and form mitochondrial 'organelle networks' with each other in which they work together as a single unit...mind-blowingly fascinating! These mitochondrial networks are just as important as neuronal networks in the brain imo). 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925334/

 

 

Since we're on the topic of fascinating mitochondrial ideas, Nick Lane talks about his mitochondrial theory of consciousness in his new book, 'Transformer', linked here: https://www.lostfalco.com/books/

 

Anyway, today we will continue our discussion of optimizing spacetime by looking at the most up to date science around 'food ordering' (ie. Does the sequence in which we eat fiber, proteins, lipids, and carbs matter?) 

 

The short answer is yes. It matters and it matters a lot!

 

Let's start with a few fundamental ideas first and then dive into the studies on healthy humans (there are a ton of human diabetic studies as well. And while we're on the subject of studies, remember my mantra: Data Over Dogma (aka The Data IS Dogma); IF the data changes, THEN I change. (full stop)).

 

Fundamental Assumption: Time is the most fundamental substance.

 

Inference from Fundamental Assumption: Therefore, IF optimize time, THEN optimize life. (or get closer to optimization, at least)

 

Temporal ordering (ie. sequencing) is a major aspect of time.

 

Application

Temporal Food Ordering: Eat Fiber/Veggies first, THEN Protein, THEN Carbs to control post-meal glucose and insulin. (Note: fat can be included with veggies (ie. olive oil dressing, for example) and/or protein (ie. fatty fish, for example).

 

Reason for Controlling Glucose/Insulin: IF control insulin/glucose, THEN control energy input into cells/mitochondria, THEN enhance everything the body does, THEN enjoy an amazing life!

 

What is your evidence for this ‘temporal food ordering’ business, Mr. Falco?

 

My own wishful thinking and warm fuzzy feelings I get in my...oh wait, nevermind. 

 

It's actually these scientific studies in healthy humans. Give in to the power of the studies…

 

 

 

Healthy Human Studies

1. Study Title: ‘Food order and glucose excursion in Indian adults with normal and overweight/obese Body Mass Index: A randomised crossover pilot trial’

 

Full Text Link: https://www.researchgate.net/profile/Ching-Li-Lee-2/publication/347829511_Food_order_and_glucose_excursion_in_Indian_adults_with_normal_and_overweightobese_Body_Mass_Index_A_randomised_crossover_pilot_trial/links/60b82ebf4585159354caea7f/Food-order-and-glucose-excursion-in-Indian-adults-with-normal-and-overweight-obese-Body-Mass-Index-A-randomised-crossover-pilot-trial.pdf

 

Lostfalco Logical Summary: IF protein first AND carb last, THEN decrease post-meal glucose response.

 

Study Conclusion: “...consuming food in the protein first/carbohydrate last order had the biggest effect in reducing PPG [postprandial glucose] excursion.” 

 

2. Study Title: ‘Postprandial glucose, insulin and incretin responses differ by test meal macronutrient ingestion sequence (PATTERN study)’ 

 

Full Text Link: https://www.uninut.org/images/material_ponentes/51/2/Postprandial_glucose_insulin_and_incretin_responses.pdf

 

Lostfalco Logical Summary: IF (Vegetable-Meat-Rice), THEN increase GLP-1, THEN lower glycemic response.

 

Study Conclusion: “Food macronutrient intake sequence can considerably influence its glycemic, insulinemic and incretin responses. V-M-R food intake sequence attenuates the glycemic response to a greater degree with accentuated GLP-1 stimulation without any increased demand for insulin. The sequence of food intake has great potential as a novel and simple behavioral strategy to modulate glycemic response in healthy adults.”

 

3. Study Title: “Consuming Carbohydrates after Meat or Vegetables Lowers Postprandial Excursions of Glucose and Insulin in Nondiabetic Subjects”

 

Full Text Link: https://www.jstage.jst.go.jp/article/jnsv/64/5/64_316/_pdf

 

Lostfalco Logical Summary: IF (veggie-meat-carb), THEN (lower post-meal glucose AND lower post-meal insulin). 

 

Study Conclusion: “We found that consuming carbohydrates at the end of the meal results in significantly lower serum glucose levels 30 min after ingestion and a lower glucose AUC at 0–120 min than those of other consumption orders. Furthermore, insulin responses at 30 min and insulin AUC at 0–120 min were lowest when carbohydrates were consumed at the end (VMC). These findings suggested that meals with the same contents but with carbohydrates consumed at the end (VMC) can control postprandial glucose levels and limit the amount of insulin necessary to control glucose levels.”

 

Q and A

Q: Do you need a break between consumption of nutrient groups? (ie. Should you eat fiber/veggies, take 5 min break, eat protein, take 5 min break, eat carbs, etc. (It’s like ‘The 20/10 Method’ for food consumption. lol) 

https://www.lostfalco.com/how-to-make-long-term-memories-in-minutes-the-2010-method/

A: This is not necessary. Some studies used no-food intervals (ie. 10min breaks or 15min breaks) but other studies showed good effects with simply eating veggies first (with olive oil usually), then protein, then carbs with no break in between. Of course, feel free to eat fiber/veggies/protein then take a 10min break and eat carbs after that if you want to test it out. However, this is not required in the literature. 

 

Q: How long should my meal last?

A: Most of the studies had meal times lasting between 15 to 30 min. I’d say a 30min meal is a reasonable time frame. 

 

Q: Does 10g of dextrin at the beginning of each meal enhance these effects?

A: Yes!

 

Q: Is Lostfalco insane?

A: Absolutely.

 

Conclusion

Food sequencing has significant, positive effects on bioenergetic response in healthy humans. The best sequence is as follows: eat fiber/veggies first, then protein, then carbohydrates. This sequence will enhance satiety to prevent overeating and optimize blood glucose levels and insulin signaling. 

 

Take 10g of the dextrin linked here before each meal as a simple, affordable way to get these results: 

http://www.lostfalco.com/supplements/

 

Happy sequence eating!

 

Upcoming posts

In the spirit of incrementalism, I've been incrementally showing you guys 'Lostfalco's Optimization Template'. We are slowly building it piece by piece; increment by increment. This template is a general framework that will allow you to create your own 'variation on a theme' (that’s what a template is for after all!). The template will be the theme (ie. what I do) and you can use it as an inspiration to create your own variation that works best for you. Think of it as a 'Day Frame' that will allow you to organize your life around the most fundamental enhancements while still having time to enjoy your life! The point is NOT to shoot light at your intrinsically photosensitive retinal ganglion cells, it's to enjoy every moment of this fleeting, temporal gift we call life. Alternately stated, the goal of life is NOT the framework, the goal of the framework is LIFE. Live it!

 

-Order is freedom. 

-Constraints are wings. 

-Constrained motion IS directed motion IS power.

-Data Over Dogma

-Simpler. Smaller. More Fundamental.

 

Blue Light: https://www.lostfalco.com/devices/

Dextrin: https://www.lostfalco.com/supplements/

Nick Lane's 'Transformer': https://www.lostfalco.com/books/

Create Flashcards: https://apps.ankiweb.net/

Edited by lostfalco, 31 October 2022 - 10:42 AM.

[Mad Scientist]

Lostfacto,

 

Thank you for your brilliant contributions, your content is remarkably elucidating. Circling back to the tDCS+D-Cycloserine element of this thread's original post :

 

Electricity--tDCS + D-cycloserine

Comments--repeated studies have shown that taking D-cycloserine 2 hours before doing tDCS causes the typical 1 hour after effects of tDCS to last for over 24 hours! Yup, that's real. This has been tested and verified in humans but, amazingly, I haven't seen any biohackers try it yet. I have a major concern about excitotoxicity on this one but I am ridiculously intrigued. Could I learn an entire semester's worth of info in a weekend? Maybe. Most of the testing has been done in the motor cortex, but I see no reason this wouldn't work in the dlpfc. Anybody tried this? I have my tDCS and a 10 pack of D-CYC in front of me but this is crazy risky. D-CYC has serious side effect potential and 24 hours of anodal excitability could very possibly fry one's brain. Not gonna try it without A LOT more knowledge. Ideas? Experiences? Would love some feedback on this intriguing idea.

 

 

Have you learned of any new literature or reports on this topic? I have a tDCS/tACS device and D-CYC on-hand. Tempted to recklessly explore in the name of science.

 

The experimental evidence for neurotrophic use with neural stimulation modalities has since grown and is now exponentially emerging. The indications as a potential replacement or adjunct for medication assisted treatment and neuroenhancement in normal subjects is promising and prevailing each day. Particularly with the recent approval of a CES device to mediate opioid receptor disturbances for detoxification. 

 

Could you propose a benign, simple teaser N=1 test for what a tDCS+D-CYC trial could look like if I wanted to take a Darwin leap?

Edited by ericzx777, 31 October 2022 - 05:37 PM.

[lostfalco]

Thank you for your brilliant contributions, your content is remarkably elucidating. Circling back to the tDCS+D-Cycloserine element of this thread's original post :

 

 

Have you learned of any new literature or reports on this topic? I have a tDCS/tACS device and D-CYC on-hand. Tempted to recklessly explore in the name of science.

Hey Mad Scientist, thanks for your kind words! I'm glad I've been able to contribute a small bit to your life. 

 

I just did a quick search of the literature and I didn't see any new articles related to the tDCS + D-Cycloserine combo. 

 

It looks like scientists stopped pursuing the combo when it didn't have beneficial (or detrimental) effects in a pilot study on depression. https://pubmed.ncbi....h.gov/23792778/

 

Other studies testing effects in the motor cortex are here: 

https://www.ncbi.nlm...les/PMC3389616/

https://www.nature.c...rticles/1300517

 

Tbh, I actually did try this ten years ago and did not notice much. That's why I like experiments so much! As long as you're safe (I imitated the human studies that showed no negative effects), it doesn't matter whether it has the effect you hope for. You learn something regardless of the outcome. 

 

As far as trying it today...as you can probably guess, I think we have MUCH more fundamental and repeatable enhancements with the power to influence cognition AND every other aspect of our bodies. 

 

The body is such an interconnected whole. The more I've experimented, the more I've become a believer in 'embodied cognition'. The body affects the brain affects the microbiome affects the external environment affects the body and on and on in a lifetime of feedback loops. Our goal to make sure the loops are virtuous and not vicious. 

 

Speaking of virtuous feedback loops....

[lostfalco]

Hello my friends!

 

I've been talking a lot lately about life enhancing effects of Central Circadian Clock Entrainment using light.

 

This, of course, begs the question: Out of the thousands of light emitting products out there, how do I choose the best one for me? (Of course, feel free to choose natural sunlight first thing in the morning!)

 

To answer this question, I tracked down a post by Yale School of Psychiatry scientists in which they tested 24 different commercially available Bright Light Therapy boxes and chose a top 7 to recommend. 

 

Their article was actually the one I originally used to help me choose my beloved SunTouch Plus light therapy box years ago.

 

Unfortunately, the SunTouch (the most affordable one on their list) has been out of stock a lot lately.

 

So, I bought the Day-Light Sky (DL2000) to test out for you guys so you'd have another option you could actually buy.

 

See my article for more details on parameters that make for an effective, safe device and how to dose properly to get the best effects. http://www.lostfalco...re-to-buy-them/

 

Anyway, I chose the Day-Light Sky (DL2000) because it's compact, affordable (relative to the large light boxes), powerful, elevated, and usually in stock. lol

 

Long story short, it works great and I highly recommend it too!

 

I also linked all seven of the devices recommended by the Yale School of Psychiatry so you guys can pick your own box to try out and see how Central Circadian Clock entrainment works for you. 

 

If you try one of the boxes out, come back and let us know how it goes!

 

Click here to get your Phot-On! (Damn, I just couldn't resist that terrible pun *shrug*): http://www.lostfalco...re-to-buy-them/

Edited by lostfalco, 03 November 2022 - 07:38 PM.

[Makiavel]

Hey Lostfalco,

 

Thank you for sharing your research. This is very interesting and you convinced me to better organize my sleeping and eating habits. 

 

Based on the promising results from the paper you linked, I am looking into dextrin, and found out that the brand you use (Benefiber) is not wheat dextrin in Canada. They use inulin instead, which could yield different results.  I am now looking for the best replacement to wheat dextrin, which I haven't found yet in Canada.

 

Have you looked into the other types of resistant starches or dextrins? Do you have any reason to prefer wheat dextrin over the other dextrins, or to prefer resistant dextrin over resistant starch?

[lostfalco]

Hey Lostfalco,

 

Thank you for sharing your research. This is very interesting and you convinced me to better organize my sleeping and eating habits. 

 

 

Hey Makiavel, no problem. Cool you're going to try some of this stuff out. I really think the syncing of the central, peripheral, and microbiome clocks is the most foundational enhancement upon which all others must be built. Keep us updated with how things go for you!

 

 

Based on the promising results from the paper you linked, I am looking into dextrin, and found out that the brand you use (Benefiber) is not wheat dextrin in Canada. They use inulin instead, which could yield different results.  I am now looking for the best replacement to wheat dextrin, which I haven't found yet in Canada.

 

Have you looked into the other types of resistant starches or dextrins? Do you have any reason to prefer wheat dextrin over the other dextrins, or to prefer resistant dextrin over resistant starch?

 

Inulin should work great. Definitely worth an experiment. I really like Now Foods inulin and it could easily replace dextrin if someone wanted to use it instead. Benefiber with inulin should be just fine.

 

I recommend dextrin because it's been shown (in vitro) to be one of the highest producers of short chain fatty acids (acetate, propionate, and butyrate) and because it is virtually tasteless and really easy to add at the beginning of a meal compared to other fibers. "The increase in concentration of all three SCFAs was the highest upon addition of Benefiber, followed by Psyllium husk and NutriKane."   https://www.ncbi.nlm...les/PMC6060387/

 

Inulin is a bit more noticeable (in liquid) and doesn't mix quite as well but it's still a great option.

 

There is going to be some variability from person to person based on differing microbiome populations (there is significant variation between individuals), but inulin, galactooligosaccharides (GOS), resistant starch, psyllium husk, etc. are all legitimate options. 

 

The main thing is to make sure you are getting enough fiber and that you are getting it on a regular schedule.  

Edited by lostfalco, 07 November 2022 - 12:05 AM.

[lostfalco]

Good morning my friends!

 

A few weeks ago I discussed substances released in response to aerobic and anaerobic exercise called myokines. https://www.longecit...131#entry918894

 

It turns out, myokines are only one small (albeit very important) part of the body's response to exercise. 

 

In fact, multiple organs throughout the body release a panoply of substances that scientists have named 'exerkines'. 

 

See this fantastic review in Nature for more on this fascinating new area of science. https://www.nature.c...574-022-00641-2

 

The main organs involved are as follows:

1. myokines - skeletal muscle

2. cardiokines - heart 

3. hepatokines - liver 

4. adipokines - white adipose tissue 

5. batokines - brown adipose tissue 

6. neurokines - nervous system

 

These substances enter the blood stream, enhance organ to organ crosstalk, and exert local as well as systemic effects throughout the entire body. 

 

Here's what it looks like...

 

 

 

Here's what it looks like in the nervous system...

 

 

For more info, see the Nature review.  https://www.nature.c...574-022-00641-2

 

To help you remember some of these ideas, I created flashcard fronts (FCF) and flashcard backs (FCB) for you to add to your Anki flashcards using key terms from the Nature article.

 

Anki is free. Download it here. https://apps.ankiweb.net/

 

Just copy the 'flashcard front' into the front of your flashcard and the 'flashcard back' into the back. 

 

Complicated, I know. lol

 

Use Spaced Generation Learning to generate answers to your flashcards by 'drawing your reference frames out loud on a spaced repetition schedule'.

 

Make sure to perform your Anki reps daily (just use their default 'spacing' algorithm) since the brain will adapt (create a memory) in response to what it repeatedly encounters (ie. temporal intervals and temporal relations are key).

 

Additionally, a simple drawing made each time you encounter a 'flashcard front' will help connect the various ideas, involve multiple brain regions (motor cortex, sensory cortex, etc.) and make them stick in your memory. 

 

I use pencil and paper to draw my reference frames and engage the motor and sensory cortices during learning and retrieval. 

 

Happy generating!

 

Note: The spacing on the 'flashcard backs' is intentional. That is how I parse sentences in order to make the logic of the statements clear to me. Feel free to adjust them to your own liking!

 

FCF: What is resilience?

FCB: the ability of the body to 

resist, 

adapt to, 

recover, or 

grow 

in response to stressors

 

FCF: What is high intensity interval training?

FCB: a form of exercise training 

characterized by bursts of high-intensity activity 

followed by less intense recovery periods.

FCF: What are exerkines?

FCB: a broad variety of signalling moieties 

that are released in response to acute and/or chronic exercise 

that exert their effects through 

endocrine, 

paracrine and/or 

autocrine pathways

FCF: What is acute exercise?

FCB: a single episode of exercise 

(often resistant or aerobic exercise)

that is completed during one visit.

FCF: What is chronic exercise?

FCB: multiple exercise episodes (often resistant or aerobic exercise) 

performed over the course 

of weeks 

to months.

FCF: What are MicroRNAs?

FCB: non-protein coding RNA molecules 

that are regulated in a transcriptional or post-transcriptional fashion 

to affect mRNA transcription and/or degradation

FCF: What are exosomes?

FCB: a type of extracellular vesicle 

released by parent cells, 

which contain 

RNAs, 

proteins and 

lipids, 

to facilitate crosstalk between tissues.

 

P.S. I'll be talking a lot more about exercise in future posts since it is literally nature's God-Stack for cognition (just look at all of those substances above!). For now, make sure you exercise at the same time every single day...and by that, I mean this...just take a 30 minute walk at the same time every day. That's it! Don't complicate it. Don't overexert yourself. Remember our fundamental beginner's principle: standardize THEN optimize. Get a daily 30 minute segment standardized for 7 days per week at the same time every day. Once that is locked in to your schedule, then you can use that time segment for resistance training, different forms of exercise, different intensity levels, etc. For now, just get it locked in at the same time everyday. No stress, no pressure. Just a relaxing stroll. 

 

I go for a 30 minute walk (or I run or lift) immediately after my 30 minutes of bright light upon waking. So, wake up, restroom, drink water then First Light (30min), then First Hike (or Bike) (30min). Corny, I know. But it rhymes!

 

I get books from audible or a podcast or a YouTube vid and listen to them at 3.5x speed (start at 2x speed and gradually increment up if you've never listened at this speed before) while I'm walking. You'll never go back to normal speed listening again. Enhance the body and brain at the same time! 

 

Sync Your Central Clock with Bright Light Therapy: http://www.lostfalco...re-to-buy-them/

Sync Your Microbiome Clock with Dextrin: https://www.lostfalco.com/supplements/

Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): https://www.lostfalco.com/devices/

Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

Edited by lostfalco, 09 November 2022 - 09:38 PM.

[lostfalco]

Hey, what's up my friends! I hope you're having a wonderful weekend. 
 
As you guys know, I'm obsessed with simple reference frames that organize vast amounts of information and allow us to see connections between disparate items of data. 
 
Given our recent focus on using light to optimize time, I've been trying to piece together a reference frame to sum up how 480nm light entrains our master central circadian clock and enhances wakefulness (and focus) throughout the day. 
 
While I was piecing together the disconnected data from various studies, I stumbled across this video by a guy named Kevin Tokoph from Catalyst University and he just nails it. 
 
When it comes to describing the process from 'Melanopsin to Melatonin' (as I like to call it) at a brain network level I really can't do a better job than Kevin does in this video. 
 
Huge props to him!
 
Pay very close attention to all of the brain regions involved and the neurotransmitters primarily used between regions. 
 
There are things we can do to optimize all of these.
 
This gives us a perfect schema around which to focus our enhancements at the brain network level (we will also focus A LOT on the intracellular/mitochondrial level in future discussions). 

 

Remember, your central circadian clock helps control the switching on and off of literally thousands of genes at the proper times in almost EVERY cell of your body.

 

There is virtually nothing more foundational than this. (ie. using light to control time)

 

Every supplement we take and every enhancement we try needs to take into account the circadian nature of the body and all of its systems.

 

All other enhancements fit in around this.
 
Anyway, it's time for me to shut up and let you guys watch this informationally dense and compact bit of simple perfection.
 
This is precisely how light works through the suprachiasmatic nucleus to enhance wakefulness.
 
Enjoy!
 

 

Here is a screenshot of our schema. Click on it to see it full size. 
 

 Screen Shot 2022-11-12 at 12.48.34 PM.png   371.35KB   0 downloads
 
 
Our Enhancements So Far:
1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/
 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/
 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/
 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

Edited by lostfalco, 12 November 2022 - 07:19 PM.

[lostfalco]

Good evening my friends! I hope you're all doing great this evening.

 

Given my level of busy-ness and life commitments I'm probably going to have to do most of my major posting on the weekends for a little while. 

 

So, I thought for my mid-week post I could select an abstract that represents an issue I'm currently studying or one that I plan to talk about in the future. 

 

Therefore...Welcome to Abstract Wednesday!

 

For the past week, I've been looking into midday bright light therapy (ie. bright light therapy between the hours of 12pm and 230pm depending on the study).

 

Check this out...

 

https://ajp.psychiat...p.2017.16101200

 

Am J Psychiatry

. 2018 Feb 1;175(2):131-139.

Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial

Dorothy K Sit 1, James McGowan 1, Christopher Wiltrout 1, Rasim Somer Diler 1, John Jesse Dills 1, James Luther 1, Amy Yang 1, Jody D Ciolino 1, Howard Seltman 1, Stephen R Wisniewski 1, Michael Terman 1, Katherine L Wisner 1

 

Abstract

Objective: Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality.

 

Method: The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less.

 

Results: At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4-6 and significantly lower depression scores (9.2 [SD=6.6] compared with 14.9 [SD=9.2]; adjusted β=-5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them.

 

Conclusions: The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.

 

Our Enhancements So Far:

 

We have our reference frame! This will be the organizing diagram around all of our future enhancements. Memorize it by attempting to draw it (generate it) until you get it down. Then, add it to your Anki flashcards and draw it on a spaced repetition schedule. Click on the pic below to make it larger.

 Screen Shot 2022-11-12 at 12.48.34 PM.png   371.35KB   0 downloads

 

1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/
 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/
 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/
 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

 

Edited by lostfalco, 17 November 2022 - 02:11 PM.

[lostfalco]

Hello my friends! I hope your weekend is going great. 

 

This is a very exciting week because now that we have our reference frame we can focus our research and center our enhancements around it. 

 

As a quick reminder, here it is...

 

 

As you can see, light is traveling from the sun, striking the retina, and sending action potentials down the retinohypothalamic tract to the suprachiasmatic nucleus to sync our master circadian clock to the light/dark cycles of the external environment.

 

So, what is happening at the interface between our retina and light?

 

Answer: Phototransduction!

 

Here's how it works....

 

 

But LF, I thought you said it was 480nm light striking intrinsically photosensitive retinal ganglion cells (ipRGCs) that mattered most. Why are you showing me a video on rods and cones?

 

Actually, ipRGCs have melanopsin in them that responds to 480nm light but they also connect to rods and cones. 

 

Here's what it looks like...

 

 

 

This is why we can use bright 'white' light therapy to enhance the synchronous firing of the suprachiasmatic nucleus...white light consists of ALL visible wavelengths equally therefore we get rod input + cone input + direct melanopsin cell activation. Win, win, win. 

 

This also why we need to dim ALL wavelengths of visible light at night in order to not stimulate these wakefulness promoting cells. Simply blocking blue light is not going to be enough unless the other wavelengths of light are dim enough to not stimulate the rods and cones that connect to ipRGCs. 

 

Fun Fact: ipRGCs are primarily on the bottom of the retina and respond strongly to light from above which is why we want our bright light therapy lamps to be above our eyes and angled down. Makes sense, ya know, since the sun is usually shining down on us from above.

 

Speaking of shining down on us from above...the brightest part of the day is the afternoon. Can we use our bright light therapy lamps then in order to sync our master circadian clock?

 

Yep.

 

As I mentioned on Abstract Wednesday, a study was performed on 46 individuals with bipolar disorder with the goal of reducing depression symptoms. 

https://ajp.psychiat...p.2017.16101200

 

A number of bipolar patients in the past had been treated with morning bright light therapy but it triggered manic episodes in a subset of them.

 

So, midday bright light therapy was tested in order to see if it might resolve depression symptoms without triggering manic episodes.

 

The treatment group received 7000 lux bright light starting at 15 minutes per day in week 1 and gradually increasing to 60 minutes per day by week 4 between 12:30 and 2:30pm.

 

The results were quite exceptional as sixty eight percent of the treatment group had remission of depression as opposed to only twenty percent of patients in the control group.

 

So, what's the takeaway for us?

 

We do not have to limit ourselves exclusively to bright light therapy in the morning. 

 

We can try it in the afternoon or possibly even try both morning AND afternoon. 

 

I'll leave it to you to decide how you want to experiment with it but I wake up at 5am and do 30 minutes then and I've also been doing 30 minutes at noon on the 4 days a week I work from home. On the three days I'm at the office I've been going outside and walking in the sun for 15 to 20 minutes after I finish my lunch at noon. 

 

There are a couple of additional reasons I do this. 

 

First, midday bright light therapy was shown to counteract the post-lunch energy dip in undergraduate students.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215386/

 

"Results showed that a post-lunch nap deprivation significantly increased subjective sleepiness and negative mood and impaired performance in PVT and PVSAT, while exposure to bright blue-enriched white light vs. normal indoor light in the early afternoon significantly relieved such negative effects on mood, sleepiness, and performance in PVSAT..."

 

Of course, this was in students who were used to taking a nap they were forced to skip so take the findings with a grain of salt. lol

 

Additionally, there is evidence that midday bright light therapy (One week of bright light treatment (2-h exposure to 2500 lux between 14.00 and 16.00 h)) can help with winter depression in humans.

https://www.scienced...165178100001384

 

Also, there is further evidence that seasonal effective disorder patients respond equally well to 2 hours of early morning or 2 hours of early afternoon bright light therapy.

https://pubmed.ncbi....ih.gov/3310669/

 

Lastly, and most importantly, there is evidence that midday bright light enhances nighttime melatonin production in humans. 

https://pubmed.ncbi....ih.gov/9121707/

 

"Furthermore, the area under the curve of nocturnal melatonin rise was significantly larger under bright light exposure than under dim light."

 

In a more recent study, bright light therapy was shown to increase nocturnal melatonin secretion and improve sleep quality in young healthy humans. 

https://journals.phy...regu.00211.2006

 

"...repeated exposures to bright light of ∼5,000 lx during the waking period for 7 days significantly increased the amplitude of nocturnal melatonin rise compared with that observed after a 5-day stay under the dim light conditions (∼10 lx)."

 

There is virtually nothing more important than quality sleep for cognition, learning, and memory! 

 

Count me in. 

 

So, there you have it.

 

Midday bright light therapy enhances mood, energy levels, nocturnal melatonin levels, and possibly sleep. 

 

That's a whole lotta goodness right there!

 

It's going on the enhancements list.

 

Until next time, LF out.

 

Our Enhancements So Far:

 

1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock. Resync your master circadian clock and enhance melatonin secretion with 30 minutes of midday bright light therapy. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/
 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/
 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/
 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

 

Edited by lostfalco, 19 November 2022 - 11:07 PM.

[lostfalco]

Hello my friends! Welcome to Abstract Wednesday. 

 

Now that we have some basic enhancements established (see the end of this post for a review) we can see the absolutely essential nature of circadian rhythms for health, mood, energy, learning, memory…everything.

 

We will continue to focus on light, food, exercise, temperature, etc. in future posts but for today I wanted to talk a little bit about something I call ‘circadian supplementation’.

 

‘Circadian Supplementation’ is supplementation that takes into account the timing rules imposed by the body’s molecular clocks. 

 

Therefore, from now on when supplementing we must take into account the time of onset of the substance, the peak, the timing of the substance within our three meal per day structure, the interaction of the substance with light, etc. 

 

Let me give you a quick example. 

 

Let’s say I was going to supplement with 50mg of caffeine. 

 

I would not take caffeine right when I wake up at 5am because my 12 hour eating window doesn’t begin until 6am. 

 

I also would not take caffeine at any time in between my meals because that would start up my digestive machinery outside of one my three meals per day and throw off my body’s digestive rhythm. (I’ll explain why this is super important in future posts. I never eat snacks between meals nor do I drink anything other than water right after waking up or between meals.)

 

I also will never take caffeine after lunch since sleep is of utmost importance, caffeine has a 5 to 6 hour half life, and caffiene disrupts sleep efficiency. (I’ll talk more about this later as well.)

 

Speaking of sleep, we also need to take substances with short enough half lives or a low enough dose so that sleep disruption is not going to occur. (For example, modafinil is going to be a challenge because of its 12 to 15 hour half-life. Not impossible though.)

 

Back to caffeine…

 

In order to supplement with it I would determine the ‘time to peak’ of caffeine (1 hour), take it with my breakfast at 6am, and then hit my retina with a dose bright light therapy at 7am right when caffeine is hitting it's peak and optimally inhibiting adenosine receptors in the retinohypothalamic tract and enhancing glutamate release into suprachiasmaic nucleus. (see the studies below on caffeine + bright light and also see our reference frame below)

 

This will help amplify the signal from the retina to the retinal ganglion cells down the RHT to the SCN. 

 

I’ll talk more about this combo later (there are SO many more!) but I just wanted to give you guys a taste of what’s coming. 

 

Long story short, virtually ALL supplements should be taken based on timing rules. (Of course, if you’re prescribed something take it as your doctor recommends!)

 

Remember, light and sleep (we will always take sleep as a given) are the foundations for everything going forward. 

 

I personally like the light therapy box because it allows me to control dosing and perform timed experiments like the one explained above.

 

For some reason the glowing hot sphere of nuclear fusion 93 million miles away doesn’t do what I tell it to. The nerve. 

 

Anyway, to give you guys a bit of a road map of what’s ahead, remember that the locus coeruleus sends extensive connections into the hippocampus and prefrontal cortex. 

 

Check this out…

 

 

We are going to be headed some crazy places in the next few months. 

 

We now have the perfect starting point for entering the brain (light to the SCN) which branches out to literally every other area of the brain and body from there.

 

I think of it like initial conditions in chaos theory. 

 

We have 30 trillion human cells and 39 trillion bacterial cells (see study below). 

 

We are trying to synchronize EVERY single one of them perfectly so that the entire superorganism that is us functions to its peak capabilities. 

 

Things are going to be massively unpredictable but if we get the starting point just right…the origin…the 0,0…we just might be able butterfly effect the f#%@ out of the rest of our brain and body and attain our perfectly balanced synchronous optimality. 

 

That’s my goal. 

 

I hope you guys are on board because that’s where we’re headed in the coming weeks and months!

 

We’re gonna use light to optimize time to optimize life.

 

We’ve got to walk before we can fly though. 

 

So, with that in mind, here is a (very) partial list of areas I’ve been looking into. 

 

Enjoy!

 

 

Levels of Study

Intracellular (nucleus to itself, clock genes)

Organelle to Organelle (mito to mito; mito to nucleus)

Cell to Cell (neuronal primarily but everything)

Set of Cells to Set of Cells (gap junctions in SCN)

Brain Region to Brain Region (neurotransmitters between brain nuclei)

Organ to Organ (exerkines)

Brain to Body (hormones)

 

 

Abstracts

 

Blue Light

 

https://pubmed.ncbi....h.gov/30674951/

Awakening effects of blue-enriched morning light exposure on university students' physiological and subjective responses

Kyungah Choi 1, Cheong Shin 2, Taesu Kim 1, Hyun Jung Chung 2, Hyeon-Jeong Suk 3

Free PMC article

Abstract

We investigated physiological and subjective responses to morning light exposure of commercially available LED lighting with different correlated colour temperatures to predict how LED-based smart lighting employed in future learning environments will impact students. The classical markers of the circadian system (melatonin and cortisol), as well as the subjective perception of sleepiness, mood, and visual comfort, were compared. Fifteen university students underwent an hour of morning light exposure to both warm (3,500 K) and blue-enriched (6,500 K) white lights at recommended illuminance levels for classrooms and lecture halls (500 lux). The decline of melatonin levels was significantly greater after the exposure to blue-enriched white light. Exposure to blue-enriched white light significantly improved subjective perception of alertness, mood, and visual comfort. With regard to cortisol, we did not find a significant difference in the cortisol decrement between the two light conditions. Our findings suggest that the sensitivity of physiological and subjective responses to white LED light is blue-shifted. These findings, extending the already known effects of short-wavelength light on human physiology, reveal interesting practical implications. Blue-enriched LED light seems to be a simple yet effective potential countermeasure for morning drowsiness and dozing off in class, particularly in schools with insufficient daylight.

 

 

https://pubmed.ncbi....h.gov/25559376/

. 2015;58(5):803-10. doi: 10.1080/00140139.2014.983300. Epub 2015 Jan 6.

Blue light aids in coping with the post-lunch dip: an EEG study

Hongchae Baek 1, Byoung-Kyong Min

Abstract

The 'post-lunch dip' is a commonly experienced period of drowsiness in the afternoon hours. If this inevitable period can be disrupted by an environmental cue, the result will be enhanced workplace performance. Because blue light is known to be a critical cue for entraining biological rhythms, we investigated whether blue light illumination can be a practical strategy for coping with the post-lunch dip. Twenty healthy participants underwent a continuous performance test, during which the electroencephalogram (EEG) was recorded under four different illumination conditions: dark ( < 0.3 lx), 33% blue-enriched light, 66% blue-enriched light and white polychromatic light. As a result, exposure to blue-enriched light during the post-lunch dip period significantly reduced the EEG alpha activity, and increased task performance. Since desynchronisation of alpha activity reflects enhancement of vigilance, our findings imply that blue light might disrupt the post-lunch dip. Subsequent exploration of illumination parameters will be beneficial for possible chronobiological and ergonomic applications.

 

 

https://pubmed.ncbi....h.gov/25526564/

. 2014 Dec 17;15(12):23448-500. doi: 10.3390/ijms151223448.

Protecting the melatonin rhythm through circadian healthy light exposure

Maria Angeles Bonmati-Carrion 1, Raquel Arguelles-Prieto 2, Maria Jose Martinez-Madrid 3, Russel Reiter 4, Ruediger Hardeland 5, Maria Angeles Rol 6, Juan Antonio Madrid 7

Abstract

Currently, in developed countries, nights are excessively illuminated (light at night), whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD), including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs) and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system.

 

 

https://pubmed.ncbi.nlm.nih.gov/31433569/

. 2019 Dec;12(12):e201900102. doi: 10.1002/jbio.201900102. Epub 2019 Sep 2.

The inner clock-Blue light sets the human rhythm

Abstract

Visible light synchronizes the human biological clock in the suprachiasmatic nuclei of the hypothalamus to the solar 24-hour cycle. Short wavelengths, perceived as blue color, are the strongest synchronizing agent for the circadian system that keeps most biological and psychological rhythms internally synchronized. Circadian rhythm is important for optimum function of organisms and circadian sleep-wake disruptions or chronic misalignment often may lead to psychiatric and neurodegenerative illness. The beneficial effect on circadian synchronization, sleep quality, mood, and cognitive performance depends not only on the light spectral composition but also on the timing of exposure and its intensity. Exposure to blue light during the day is important to suppress melatonin secretion, the hormone that is produced by the pineal gland and plays crucial role in circadian rhythm entrainment. While the exposure to blue is important for keeping organism's wellbeing, alertness, and cognitive performance during the day, chronic exposure to low-intensity blue light directly before bedtime, may have serious implications on sleep quality, circadian phase and cycle durations. This rises inevitably the need for solutions to improve wellbeing, alertness, and cognitive performance in today's modern society where exposure to blue light emitting devices is ever increasing.

 

 

Caffeine + Bright Light

https://pubmed.ncbi....h.gov/35398627/

. 2022 May;93:15-25. doi: 10.1016/j.sleep.2022.03.013. Epub 2022 Mar 24.

Bright light alone or combined with caffeine improves sleepiness in chronically sleep-restricted young drivers

Shamsi Shekari Soleimanloo 1, Veronica Garcia-Hansen 2, Melanie J White 3, M Mamun Huda 4, Simon S Smith 4

Abstract

Background: Young drivers are over-involved in sleepiness-related crashes. The alerting effects of bright light offer a potential countermeasure for driver sleepiness, either replacing or in conjunction with current countermeasures such as the use of caffeine.

Methods: Thirty young (18-25) chronically sleep-restricted drivers drove in a simulator under randomized conditions of continuous bright light ('Light,' 500 nm, 230μw/cm2), caffeine ('Caffeine,' 100 mg caffeinated gum), or light and caffeine together ('Light + Caffeine'), after driving under a placebo condition ('Placebo,' decaffeinated gum, 555 nm light, 0.3 μW/cm2) on three consecutive days. Using mixed-effects linear models, the associations between these conditions and physiological outcomes (EEG alpha and theta power, heart rate, and beat-to-beat intervals), driving performance (lateral lane and steering-related outcomes and lateral acceleration), and subjective sleepiness was assessed.

Results: Relative to Placebo, all conditions improved driving performance outcomes (P < 0.0001), with effects of Light + Caffeine equal to Light but greater than Caffeine. Light + Caffeine reduced EEG alpha power more than Light or Caffeine (P < 0.0006), but ECG outcomes were generally worse under all conditions relative to Placebo. Subjective sleepiness improved under the Light + Caffeine condition only (P < 0.0001).

Conclusions: Combining bright light and caffeine enhances their alerting effects on lateral lane variability and subjective sleepiness. A bright light could be a practical alternative to caffeine for sleepy drivers who avoid caffeine. The alerting effects of bright light could alleviate chronic community-level mild sleep restriction and provide on-road benefits to reduce severe injuries and fatal sleepiness-related crashes.

 

 

Lithium

https://pubmed.ncbi....h.gov/33650218/

. 2021 Aug;23(5):445-453. doi: 10.1111/bdi.13070. Epub 2021 Mar 16.

Effect of lithium on circadian rhythm in bipolar disorder: A systematic review and meta-analysis

Ni Xu 1, Kiyomi Shinohara 2, Kate E A Saunders 1 3, John R Geddes 1 3, Andrea Cipriani 1 3

Abstract

Objectives: Circadian rhythm disruption is commonly reported in patients with bipolar disorder. Lithium has been suggested to have effects on the circadian clock, the biological basis of the circadian rhythm. The objective of the current review was to review systematically the existing studies on the effect of lithium on circadian rhythm in patients with bipolar disorder.

Methods: We systematically searched the scientific literature up to September 2020 for experimental or observational studies which measured circadian rhythm in bipolar patients taking lithium (in comparison with placebo or other active treatments) and carried out a meta-analysis. Circadian rest-activity was our primary outcome, but we also collected data about sleep quality and chronotype (Morningness-Eveningness). The protocol was registered in PROSPERO (CRD42018109790).

Results: Four observational studies (n = 668) and one experimental study (n = 29) were included. Results from the meta-analysis suggest a potential association between lithium and shifts towards morningness (standardized mean difference [SMD]: 0.42, 95% confidence interval [CI]: -0.05 to 0.90). One cohort study with 21 days of follow-up found that patients treated with lithium had significantly larger amplitude (0.68, 0.01 to 1.36) when compared to anticonvulsants.

Conclusion: This review highlights the insufficient evidence to inform us about the effect of lithium on circadian rhythm. However, we found that chronotype can be a potential target for further exploration of biomarkers or biosignatures of lithium treatment in patients with bipolar disorder. Further studies with prospective and longitudinal study design, adopting actigraphy to monitor daily circadian rest-activity changes are needed.

 

 

Bright Light Therapy + Methylphenidate (Ritalin/Concerta) + Melatonin

. 2021 Jun;11(2):170-179. doi: 10.1136/bmjspcare-2019-001877. Epub 2020 Jan 10.

Sleep disturbance in patients with cancer: a feasibility study of multimodal therapy

Sriram Yennurajalingam 1, Cindy Carmack 2, Dave Balachandran 3, Cathy Eng 4, Bora Lim 5, Marvin Delgado 2, Diana Guzman Gutierrez 2, Monica Raznahan 2, Minjeong Park 6, Kenneth R Hess 6, Janet L Williams 2, Zhanni Lu 2, Jewel Ochoa 2, Eduardo Bruera 2

Abstract

Background: Our aim was to determine feasibility and effect sizes of bright light therapy (BLT), melatonin (MLT), methylphenidate (MP) and eight combinations (BLT+MLT+MP, BLT+MLT, BLT+MP, BLT alone, MLT+MP, MLT alone, MP alone, placebo for BLT, MLT and MP) defined as multimodal therapy (MMT), to improve sleep quality (SQ) (Pittsburgh Sleep Quality Index (PSQI)) from baseline to day 15. We also examined the effects of MMT on insomnia, fatigue, depression, quality of life and actigraphy.

Methods: Patients with advanced cancer with poor SQ (PSQI ≥5) were eligible. Using a double-blind randomised factorial study design, patients were randomised into 1 of the 8 arms for 2 weeks. Feasibility and effect sizes were assessed.

Results: 81% (54/67) of randomised patients completed the study. There were no differences in the demographics and SQ between groups. The adherence rates for BLT, MLT and MP were 93%, 100% and 100%, respectively. BLT+MLT+placebo of MP; BLT+placebo of MLT+placebo of MP; BLT+MLT+MP showed an effect size (Cohen's d) for change in PSQI scores of 0.64, 0.57 and 0.63, respectively. PSQI change using linear regression showed BLT (n=29) has effect size of 0.46, p=0.017; MLT (n=26), 0.24, p=0.20; MP (n=26), 0.06, p=0.46. No significant differences were observed in scores for insomnia, fatigue, depression, quality of life and actigraphy. There were no differences in adverse events by groups(p=0.80).

Conclusions: The use of MMT to treat SQ disturbance was feasible. BLT+MLT showed the most promising effect size in improvement in SQ, and additional larger studies are needed.

 

 

Human Cells vs. Bacterial Cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991899/

PLoS Biol. 2016 Aug; 14(8): e1002533.

Published online 2016 Aug 19. doi: 10.1371/journal.pbio.1002533

Revised Estimates for the Number of Human and Bacteria Cells in the Body

Ron Sender,1 Shai Fuchs,2,¤* and Ron Milo1,*

Author information Copyright and License information Disclaimer

Abstract

Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.

 

 

Dopamine

. 2017 Aug 21;27(16):2465-2475.e3. doi: 10.1016/j.cub.2017.06.084. Epub 2017 Aug 3.

Direct Midbrain Dopamine Input to the Suprachiasmatic Nucleus Accelerates Circadian Entrainment

Ryan M Grippo 1, Aarti M Purohit 1, Qi Zhang 1, Larry S Zweifel 2, Ali D Güler 3

Free PMC article

Abstract

Dopamine (DA) neurotransmission controls behaviors important for survival, including voluntary movement, reward processing, and detection of salient events, such as food or mate availability. Dopaminergic tone also influences circadian physiology and behavior. Although the evolutionary significance of this input is appreciated, its precise neurophysiological architecture remains unknown. Here, we identify a novel, direct connection between the DA neurons of the ventral tegmental area (VTA) and the suprachiasmatic nucleus (SCN). We demonstrate that D1 dopamine receptor (Drd1) signaling within the SCN is necessary for properly timed resynchronization of activity rhythms to phase-shifted light:dark cycles and that elevation of DA tone through selective activation of VTA DA neurons accelerates photoentrainment. Our findings demonstrate a previously unappreciated role for direct DA input to the master circadian clock and highlight the importance of an evolutionarily significant relationship between the circadian system and the neuromodulatory circuits that govern motivational behaviors.

 

 

Our Enhancements So Far:

 

1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock. Resync your master circadian clock and enhance melatonin secretion with 30 minutes of midday bright light therapy. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/

 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/

 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/

 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

 

 

Our Reference Frame

 

Edited by lostfalco, 27 November 2022 - 04:43 PM.

[lostfalco]

Good morning my friends! Happy Thanksgiving to everyone celebrating today and Happy Day to everyone around the world whether you are celebrating or not. 

 

Since I'm thankful for you guys listening to all my craziness I figured I would give back by giving you four quick tips for avoiding the post Thanksgiving meal food coma. 

 

Here we go....

 

Tip #1: If you can, try and drink your dextrin right before the meal. I know it's a little weird to drink fiber in front of extended family and friends but that influx of dextrin will prime your digestive system and prepare it for the large meal that's coming.

 

Tip #2: Remember to use 'Sequence Eating'. If you have veggies/fiber then eat them first. If not, eat your turkey/meat first before getting to the carbs and desert in the second part of the meal.

 

Tip #3: Eat slowly. Remember that it takes a while for your stomach and brain to communicate your level of fullness. Try to savor each bite and take a little break here and there to chat with family or friends sitting near you. This will help prevent excessive overeating and the coma that follows. 

 

Tip #4: Go for a 15 to 30 minute walk right after the meal. If you can do this, this will help immensely. Being upright and moving around enhances gastric motility, significantly improves glycemic response, and will help you avoid the usual tiredness that follows a meal. (see study below) Personally, I take a 15 minute walk after just about every meal. Makes a huge difference.

 

There you go. Four tips for a great day. 

 

Have a wonderful Thursday!

 

 

https://www.ncbi.nlm...les/PMC8912639/

 

The Effects of Postprandial Walking on the Glucose Response after Meals with Different Characteristics

Alessio Bellini, Andrea Nicolò, [...], and Massimo Sacchetti

Abstract

We evaluated the effect of postprandial walking on the post-meal glycemic response after meals with different characteristics. Twenty-one healthy young volunteers participated in one of two randomized repeated measures studies. Study 1 (10 participants) assessed the effects of 30 min of brisk walking after meals with different carbohydrate (CHO) content (0.75 or 1.5 g of CHO per kg/body weight). Study 2 (11 participants) evaluated the effects of 30 min of brisk walking after consuming a mixed meal or a CHO drink matched for absolute CHO content (75 g). Postprandial brisk walking substantially reduced (p < 0.009) the glucose peak in both studies, with no significant differences across conditions. When evaluating the glycemic response throughout the two hours post-meal, postprandial walking was more effective after consuming a lower CHO content (Study 1), and similarly effective after a mixed meal or a CHO drink (Study 2), although higher glucose values were observed when consuming the CHO drink. Our findings show that a 30 min postprandial brisk walking session improves the glycemic response after meals with different CHO content and macronutrient composition, with implications for postprandial exercise prescription in daily life scenarios.

 

Edited by lostfalco, 24 November 2022 - 11:33 AM.

[lostfalco]

Hello my friends! I hope you’re having a wonderful weekend. 

 

I hope you guys are as excited as I am that we have THE perfect starting point for ALL future enhancements. 

 

If we can master the upstream then literally EVERYTHING downstream will have an incredible probability of taking care of itself. 

 

To illustrate this fact let me quote in full a section from Dr. Satchin Panda’s (the revolutionary discoverer of melanopsin in the retina and Salk Institute Biology Professor) fantastic book ‘The Circadian Code’...(linked here https://www.lostfalco.com/books  )

 

“SCN: The Master Clock - Scientists knew that cells communicated with each other, but we wondered if our internal clocks communicated from organ to organ. Scientists found a small cluster of cells that function as a master clock—just like atomic clocks are the master clocks for all other clocks in the world. These cells, collectively known as the suprachiasmatic nucleus, or SCN, are strategically located at the hypothalamus, the center of the base of the brain, which houses the command centers for hunger, satiety, sleep, fluid balance, the stress response, and more. The 20,000 cells that make up the SCN are indirectly connected to the pituitary gland, which produces growth hormone; the adrenal glands, which release stress hormones; the thyroid gland, which produces thyroid hormones; and the gonads, which produce reproductive hormones. The SCN is also indirectly connected to the pineal gland, which produces the sleep hormone melatonin.

 

Panda, Satchin. The Circadian Code (p. 31). Harmony/Rodale. Kindle Edition.” 

 

Here’s what it looks like drawn out…

 

 Screen Shot 2022-11-27 at 10.07.20 AM.png   742.78KB   0 downloads
 

As you can see, we have at our fingertips the master controller of everything the body does. 

 

What is so incredible to me is that we have only 10,000 ipRGCs in the retina and 20,000 cells in the SCN that thereby give us control over all 68 trillion cells of the human super-organism.

 

Pretty damn amazing. 

 

In light of this knowledge and given my desire to be in control of my 68 trillion cells, I’ve created my own ‘Day Frame’ that I organize my life around using these master regulators of light, food, exercise, and temperature (especially light!).

 

Some of these items I’ve justified scientifically for you guys in previous posts while others I have yet to talk about. 

 

Suffice it to say, I have a reason for everything I do and every decision I make. 

 

Back of the envelope cost-benefit analyses are always carried out and decisions are made to best optimize my life in light of current circumstances (ie. I would choose an 8 or 10 hour eating window in an ideal world).

 

Of course, trial and error experimentation informed by the latest science combined with iterative incremental improvement are a must.

 

Think of my ‘Day Frame’ as a template you can use to create your own Day Frame that works for you.

 

None of us are exactly the same and there will inevitably be variations from person to person.

 

With that said, here’s what I’m doing right now. This is the foundation upon which all other enhancements and all Circadian Supplementation must take place for me. 

 

Take a look...

 

Lostfalco’s Day Frame

 

5:00am - First Light: wake up, use restroom, drink 16 to 32 ounces water, bright light lamp for 30 min

5:30am - First Hike/Bike: exercise (cardio Mon, Wed, Fri, Sun; weights Tues, Thur, Sat)

6:00am - First Bite: 12 hour eating window starts; 50% of daily calories consumed at breakfast; high protein = >30g; main staples are fiber/dextrin, kale, fatty fish/oysters, extra virgin olive oil, whole eggs, blueberries

6:00am - First Type: fiber/veggies first, then protein, then carbs (sequence eating)

6:30am - stop eating, 15 min walk (outside in the sun if possible)

6:45 am to 11:30am - no food, snacks or drinks with calories; only water

11:30am - lunch; 30% of daily calories consumed at lunch; sequence eating

12:00pm - stop eating, 15 min walk (outside in the sun if possible)

12:15pm - midday bright light lamp for 30min

12:15pm to 5:30pm - no food, snacks or drinks with calories; only water

5:30pm - dinner; 20% of daily calories consumed at dinner; sequence eating

6:00pm - stop eating; 12 hour eating window closes; no food, snacks or drinks with calories; only water until 6am the following day; 15 minute walk (outside in the sun if possible)

8:00pm - turn AC down to 67°F (19.4°C); dim lights and computer screens for the rest of the evening

10:00pm - lights out, sleeping mask, white noise or air purifier or loud fan, blackout curtains

 

Anyway, I hope that gives you an idea of the frame I've created for myself each day.

 

It's amazing how freeing it is to have all of those decisions made ahead of time.

 

It truly gives my life an amazing rhythmicity to it.

 

Additionally our brains LOVE patterns and prediction.

 

This gives my brain a very nice pattern and allows it to have a measure of predictive capacity over the coming day.

 

There is A LOT of peace in this.

 

With all of that said, here are a few principles and ideas that I use to guide my research and experiments.

 

Feel free to disagree!

 

These are just my opinions and I realize there are 8 billion people in the world and 8 billion different worldviews. lol

 

Guiding Principles

 

Goal: My Ideal Life 

Means: B3 - Perfect synchronization of Brain, Body, and Biome

Method: A4 - Aim, Act, Attend, Adjust

 

 Screen Shot 2022-11-27 at 10.07.59 AM.png   298.77KB   0 downloads

 

First person conscious mental states are the starting point for everything. However, I believe the external world exists.

 

Spacetime is the most fundamental substance. Therefore, mastering spacetime will increase my probability of mastering my life. Master light, master time, master life.

 

All reality is physical (ie. there are no gods, spirits, demons, angels, non-physical monsters, etc; mental states, conscious states, beliefs, desires, etc are physical). Therefore, mastering my physical reality IS what it means to master myself. Hence, focus on physical realities. (ie. light, oxygen, water, food, energy, information, elements, etc.)

 

The GREATEST power is power over ONESELF.

 

Always think from a first person perspective (ie. imagine the beginning of the universe from a first person perspective and NOT from a third person perspective. A third person perspective ASSUMES waayyy too much and will lead you intellectually astray). We are IN the universe comparing things WITHIN the universe. NEVER assume omniscience or a stance outside spacetime. Our human categories of thought were created within the universe and cannot be extrapolated outside of it. In fact, 'outside' the universe doesn't mean anything. It is a squared circle; it is one hand clapping. 

 

ALL comparisons/measurements are made from inside the universe using other things inside the universe.

 

Constraints are freedom.

 

Take sleep as a given.

 

Go to bed at the same time and wake up at the same time EVERY day, 7 days per week. 

 

‘Weeks’ are arbitrary and made up. ‘Months’ are based on lunar cycles which do not affect us that much. Days (approx 24 hours, Earth’s rotation on its 23.5° axis) and years (Earth’s orbit around the sun) are physical, objective, measurable and non-arbitrary and we evolved with their existence already in place (Sun is 4.6 billion years old, Earth is 4.5 billion years old, Microbes are 4 billion years old, and Humans are 300,000 years old…the external environment (light, atmosphere, elements, microbes, etc) came first). I evolved around THEM and from them. Take this as a given and learn from it. ‘Weekends’ don’t exist except as a social construct. Create a 24 hour pattern that you can repeat EVERY day of the YEAR.

 

The secret to life the universe and everything is NOT 42…it’s 24. Master every 24 hour cycle. 

 

Other people fit in around MY frame for me. My life is MINE and their life is theirs. They can fit into my frame or not. Up to them based on their own frame and their own desires.

 

Eat meals at the same time every day. Use Sequence Eating. 

 

Exercise at the same time every day.

 

‘Do, Not-Do Duality’ - Not doing X is just as important as doing X.  

Not-awake is just as important as awake.

Not-eating is just as important as eating.

Not-exercising is just as important as exercising.

Not-learning is just as important as learning.

Not-scheduled time is just as important as scheduled time.

 

Think in action cardinality and action ordinality.

 

‘The Plus-One Threshold’ - if you slightly increment (+1) multiple areas over time so that you are eventually  incrementing MANY simultaneously, THEN you will eventually reach a threshold that, once crossed, will take you to a new level previously unavailable to you. Think of the strong nuclear force overcoming electromagnetism at short distances.

 

I am constantly being broken down and built back up. I am a homeostatic star constantly balancing the inward crush of gravity with the outward explosive force of nuclear fusion. Therefore, balancing the opposing forces of collapse and expansion is essential. 

 

There are master inflection points such that IF ONE, THEN ALL…ie. IF you take care of ONE thing, THEN it will take care of ALL things. Always search assiduously for such points. 

 

Practice radical simplification.

 

Focus ALL on ONE.

 

Simpler, Smaller, More Fundamental

 

I must constantly reorder myself to fight the disordered pull of entropy. Since I am constantly rebuilding I MUST give my body the best energy to rebuild and the best raw materials to rebuild with.

 

The brain is a prediction engine. The brain changes itself in light of the FREQUENCY of past events in order to prepare itself to encounter those events in the future. It is using it’s precious, scarce energy to build a predictive model of the world to guide future action outputs at the whole organism level.

 

The body is designed for survival movements and reproductive movements...it is designed for movement/output. Use this to your advantage by increasing your outputs/actions.

 

Always focus on the simplest possible actions. (see Turing)

 

The most fundamental area of human thought is discrete mathematics. Master the fundamentals of the most fundamental thing.

 

Always search for positive feedback loops. Use energy to create energy. Use intelligence to create intelligence. Use resources to create resources. Use money to create money. 

 

Invest in yourself, master yourself…and you will have the power to master anything.

 

Be logical in thought and ordered in action.

 

Be rational. Always.

 

Output is king. Always focus on what you are outputting (ie. words, drawings, writings, movements, etc.) 

 

Affect the area around you like a charged particle. 

 

Like the brain, the body is also a prediction engine. The body changes itself in light of the frequency of past events. Frequent past cardio events change the cardiovascular system to prepare to encounter similar future cardio events AND frequent past weight training events change the muscular system (by growing bigger muscles) to prepare for future similar weight training events. It’s prediction all the way down. Thus, prediction is a key to biological success and deserves intense focus.

 

The brain, body, and biome are a superorganism of massively interconnected communication in a rhythmic fashion. 

 

Exerkines are the body, brain and biome communicating with each other with the purpose of making adjustments to anticipate the future. 

 

The reported ‘mind-muscle connection’ is very possibly exerkine related. ‘Thinking’ about the muscle might release neurokines that affect muscle growth and repair.

 

Always increment. 

 

Think in the BROADEST possible frames (ex. the diameter of the universe) and the NARROWEST possible frames (ex. the Planck length)...and always frame middle events within those two extremes. 

 

Free will does not exist. Therefore, be careful when you judge.

 

99.999% of everything your brain does is subconscious. NEVER forget that. 

 

Attempt to change no one except yourself. 

 

Make every possible subconscious assumption conscious. 

 

Beware of subconscious, unconsidered mental anchor points. Make ALL your anchors/reference points explicit. 

 

Data Is Dogma. I always reserve the right to change any and ALL beliefs in light of new data. My starting point is DIRECT observation NOT theoretical assumption. Either make the direct observation myself or learn from the person who made the direct observation. Make the ‘game of telephone’ have as few connections as possible. IF it contradicts experiment, THEN it’s wrong. 

 

Our Enhancements So Far:

 

1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock. Resync your master circadian clock and enhance melatonin secretion with 30 minutes of midday bright light therapy. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/

 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/

 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/

 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

 

 

Our Reference Frame

 

 Screen Shot 2022-11-12 at 12.48.34 PM.png   371.35KB   0 downloads

Edited by lostfalco, 28 November 2022 - 10:20 PM.

[Lsdium]

This last post was gold and beautiful Lostfalco. Thank you!

Keep up with your work! Love to take these small nuggets from you and try applying that to my life.

 

[lostfalco]

This last post was gold and beautiful Lostfalco. Thank you!

Keep up with your work! Love to take these small nuggets from you and try applying that to my life.

 

Thanks Lsdium! I really appreciate that. Truly. 

 

Tbh, I haven't had much feedback in a while so I was starting to wonder if I've really been helping anyone.  

 

It's really good to hear that you've found some bits to add to your life. 

 

I've honestly been having a blast diving headfirst into all of this research and it's been helping me so there's always that. lol

 

There are SO many more things that I can't wait to share so hopefully they'll be some more things coming that you'll find useful.

 

Anyway, thanks again for your kind words. It means a lot. 

[lostfalco]

Hello my friends! I hope your Abstract Wednesday is going great.

 

I have some REALLY exciting studies to show you guys today and I'll be talking more about them this weekend. 

 

It turns out that intrinsically photosensitive retinal ganglion cells follow one pathway into the brain to enhance learning and a newly discovered pathway into the brain to enhance mood. 

 

I f#$@ing love scientific surprises!

 

This is what makes science so damn amazing. 

 

I present to you the...drum roll...the mood enhancing perihabenular nucleus (PHb). 

 

This is SO freaking exciting. 

 

We are going to be able to help A LOT of people with a brand new first line treatment for not just Seasonal Effective Disorder (SAD) but also Major Depressive Disorder (MDD). 

 

Check this out...

 

The Perihabenular Nucleus (PHb)

 

 

 

 

https://www.ncbi.nlm...les/PMC6190605/

Light Affects Mood and Learning through Distinct Retina-Brain Pathways

Abstract

Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood and cognitive functions is well established, viz. intrinsically photosensitive retinal ganglion cells (ipRGCs), the central mediators are unknown. Here, we reveal that the direct effects of light on learning and mood utilize distinct ipRGC output streams. ipRGCs that project to the suprachiasmatic nucleus (SCN) mediate the effects of light on learning, independently of the SCN's pacemaker function. Mood regulation by light, on the other hand, requires an SCN-independent pathway linking ipRGCs to a previously unrecognized thalamic region, termed perihabenular nucleus (PHb). The PHb is integrated in a distinctive circuitry with mood-regulating centers and is both necessary and sufficient for driving the effects of light on affective behavior. Together, these results provide new insights into the neural basis required for light to influence mood and learning.

 

https://pubmed.ncbi....h.gov/30241611/

A Thalamic Circuit Lights up Mood
Abstract

The contributions of areas downstream of retinal ganglion cells involved in the processing and regulation of mood remain largely unspecified. In this issue of Cell, Fernandez et al. (2018) identify a thalamic circuit within the perihabenular region (pHb) linking daily changes of light pattern to mood regulation.

 

 

https://www.ncbi.nlm...les/PMC9187232/

Daily changes in light influence mood via inhibitory networks within the thalamic perihabenular nucleus

Abstract

Exposure to irregular lighting schedules leads to deficits in affective behaviors. The retino-recipient perihabenular nucleus (PHb) of the dorsal thalamus has been shown to mediate these effects in mice. However, the mechanisms of how light information is processed within the PHb remains unknown. Here, we show that the PHb contains a distinct cluster of GABAergic neurons that receive direct retinal input. These neurons are part of a larger inhibitory network composed of the thalamic reticular nucleus and zona incerta, known to modulate thalamocortical communication. In addition, PHbGABA neurons locally modulate excitatory-relay neurons, which project to limbic centers. Chronic exposure to irregular light-dark cycles alters photo-responsiveness and synaptic output of PHbGABA neurons, disrupting daily oscillations of genes associated with inhibitory and excitatory PHb signaling. Consequently, selective and chronic PHbGABA manipulation results in mood alterations that mimic those caused by irregular light exposure. Together, light-mediated disruption of PHb inhibitory networks underlies mood deficits.

 

https://www.ncbi.nlm...les/PMC8781294/

Multi-Level Processes and Retina-Brain Pathways of Photic Regulation of Mood

Abstract

Light exerts powerful biological effects on mood regulation. Whereas the source of photic information affecting mood is well established at least via intrinsically photosensitive retinal ganglion cells (ipRGCs) secreting the melanopsin photopigment, the precise circuits that mediate the impact of light on depressive behaviors are not well understood. This review proposes two distinct retina-brain pathways of light effects on mood: (i) a suprachiasmatic nucleus (SCN)-dependent pathway with light effect on mood via the synchronization of biological rhythms, and (ii) a SCN-independent pathway with light effects on mood through modulation of the homeostatic process of sleep, alertness and emotion regulation: (1) light directly inhibits brain areas promoting sleep such as the ventrolateral preoptic nucleus (VLPO), and activates numerous brain areas involved in alertness such as, monoaminergic areas, thalamic regions and hypothalamic regions including orexin areas; (2) moreover, light seems to modulate mood through orexin-, serotonin- and dopamine-dependent pathways; (3) in addition, light activates brain emotional processing areas including the amygdala, the nucleus accumbens, the perihabenular nucleus, the left hippocampus and pathways such as the retina-ventral lateral geniculate nucleus and intergeniculate leaflet-lateral habenula pathway. This work synthetizes new insights into the neural basis required for light influence mood.

 

https://pubmed.ncbi....h.gov/32483349/

A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice

Abstract

Besides generating vision, light modulates various physiological functions, including mood. While light therapy applied in the daytime is known to have anti-depressive properties, excessive light exposure at night has been reportedly associated with depressive symptoms. The neural mechanisms underlying this day-night difference in the effects of light are unknown. Using a light-at-night (LAN) paradigm in mice, we showed that LAN induced depressive-like behaviors without disturbing the circadian rhythm. This effect was mediated by a neural pathway from retinal melanopsin-expressing ganglion cells to the dorsal perihabenular nucleus (dpHb) to the nucleus accumbens (NAc). Importantly, the dpHb was gated by the circadian rhythm, being more excitable at night than during the day. This indicates that the ipRGC→dpHb→NAc pathway preferentially conducts light signals at night, thereby mediating LAN-induced depressive-like behaviors. These findings may be relevant when considering the mental health effects of the prevalent nighttime illumination in the industrial world.

 

https://pubmed.ncbi....h.gov/33129807/

The relevance of daylight for humans

Abstract

Daylight is ubiquitous and is crucial for mammalian vision as well as for non-visual input to the brain via the intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin. The ipRGCs project to the circadian clock in the suprachiasmatic nuclei and thereby ensure entrainment to the 24-hour day-night cycle, and changes in daylength trigger the appropriate seasonal behaviours. The ipRGCs also project to the perihabenular nucleus and surrounding brain regions that modulate mood, stress and learning in animals and humans. Given that light has strong direct effects on mood, cognition, alertness, performance, and sleep, light can be considered a "drug" to treat many clinical conditions. Light therapy is already well established for winter and other depressions and circadian sleep disorders. Beyond visual and non-visual effects via the retina, daylight contributes to prevent myopia in the young by its impact on eye development, and is important for Vitamin D synthesis and bone health via the skin. The sun is the most powerful light source and, dependent on dose, its ultraviolet radiance is toxic for living organisms and can be used as a disinfectant. Most research involves laboratory-based electric light, without the dynamic and spectral changes that daylight undergoes moment by moment. There is a gap between the importance of daylight for human beings and the amount of research being done on this subject. Daylight is taken for granted as an environmental factor, to be enjoyed or avoided, according to conditions. More daylight awareness in architecture and urban design beyond aesthetic values and visual comfort may lead to higher quality work and living environments. Although we do not yet have a factual basis for the assumption that natural daylight is overall "better" than electric light, the environmental debate mandates serious consideration of sunlight not just for solar power but also as biologically necessary for sustainable and healthy living.

 

https://www.nature.c...1583-020-0332-0

Light darkens mood

Abstract

Increased light exposure at night can exacerbate depressive symptoms. Here, increased light exposure at night in mice increased depressive-like symptoms. The authors mapped a retina-to-dorsal perihabenular nucleus (dpHb)-to-nucleus accumbens (NAcc) pathway that was more excitable at night than during the day and found that the resulting increase in activation of the NAcc could underlie the depressive-like behaviours. These findings could have implications for the effects of artificial light and mental health.

https://www.ncbi.nlm...les/PMC7445808/

How Does Light Regulate Mood and Behavioral State?

Abstract

The idea that light affects mood and behavioral state is not new. However, not much is known about the particular mechanisms and circuits involved. To fully understand these, we need to know what properties of light are important for mediating changes in mood as well as what photoreceptors and pathways are responsible. Increasing evidence from both human and animal studies imply that a specialized class of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs), plays an important role in the light-regulated effects on mood and behavioral state, which is in line with their well-established roles in other non-visual responses (pupillary light reflex and circadian photoentrainment). This paper reviews our current understanding on the mechanisms and paths by which the light information modulates behavioral state and mood.

 

 

Bright Light Therapy + Antidepressants

 

https://pubmed.ncbi....h.gov/31600678/

Efficacy of light therapy versus antidepressant drugs, and of the combination versus monotherapy, in major depressive episodes: A systematic review and meta-analysis

Abstract

Although light therapy (LT) has been shown to be efficient in the treatment of seasonal and non-seasonal depression, it is underused in clinical settings and antidepressant drugs (AD) remain so far the usual first line treatment. The aim of this systematic review and weighted random effect meta-analysis is to examine the randomized controlled trials that compared directly light therapy and antidepressant drugs, as well as their combination (LT + AD). A total of 397 participants were included, with a moderate to severe major depressive episode, from seven independent populations. The median duration of intervention was 5 wks (range 2-8 wks). The superiority (lower depression score) of LT + Placebo compared to AD + Placebo was non-significant (SMD = 0.19 [-0.08-0.45]; p = 0.17). The combination LT + AD was superior to AD + Placebo (SMD = 0.56 [0.24-0.88]; p < 0.001). This superiority was confirmed in the subgroup of patients with non-seasonal depression (SMD = 0.55 [0.16-0.93]; p = 0.005). Meta-analyses showed no or small heterogeneity between studies (I2 = 0%, 18.41%, and 39.23% respectively). No potential publication biases were observed by statistical tests and visual inspection of the funnel plots. No differences were observed between LT and AD, with a clear superiority of the combination, thus both LT monotherapy and combination may be proposed as a first line treatment in seasonal and non-seasonal depression.

 

 

Our Enhancements So Far:

 

1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Get 7 to 9 hours of sleep. Full stop. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock and enhance your ability to sleep that night. Resync your master circadian clock and enhance melatonin secretion with 30 minutes of midday bright light therapy. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/

 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/

 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/

 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

 

Our Reference Frame

 

 

 

Lostfalco's Day Frame

 

5:00am - First Light: wake up, use restroom, drink 16 to 32 ounces water, bright light lamp for 30 min

5:30am - First Hike/Bike: exercise (cardio Mon, Wed, Fri, Sun; weights Tues, Thur, Sat)

6:00am - First Bite: 12 hour eating window starts; 50% of daily calories consumed at breakfast; high protein = >30g; main staples are fiber/dextrin, kale, fatty fish/oysters, extra virgin olive oil, whole eggs, blueberries

6:00am - First Type: fiber/veggies first, then protein, then carbs (sequence eating)

6:30am - stop eating, 15 min walk (outside in the sun if possible)

6:45 am to 11:30am - no food, snacks or drinks with calories; only water

11:30am - lunch; 30% of daily calories consumed at lunch; sequence eating

12:00pm - stop eating, 15 min walk (outside in the sun if possible)

12:15pm - midday bright light lamp for 30min

12:15pm to 5:30pm - no food, snacks or drinks with calories; only water

5:30pm - dinner; 20% of daily calories consumed at dinner; sequence eating

6:00pm - stop eating; 12 hour eating window closes; no food, snacks or drinks with calories; only water until 6am the following day; 15 minute walk (outside in the sun if possible)

8:00pm - turn AC down to 67°F (19.4°C); dim lights and computer screens for the rest of the evening

10:00pm - lights out, sleeping mask, white noise or air purifier or loud fan, blackout curtains

 

Edited by lostfalco, 01 December 2022 - 07:37 PM.

[lostfalco]

Holy mother of god...I think legitimate IQ increase might actually be possible now and I know exactly how to try it. 

 

Guys, this experiment is going to be the most reckless thing I've ever attempted but I have to try it. 

 

And I'm not exaggerating when I say that to my knowledge it will be a first in human history. 

 

You'll see when I tell you what I'm going to do. haha (I'll tell you my exact dosages and substances in a few weeks once I've researched a bit more)

 

My girlfriend is going out of town around Christmas time so I'll have a friend come over and watch me and I'll dose and get on here and share my experience in real time with you guys. 

 

I'll let you know the date soon.

 

Anyway, if you guys remember a few months ago I talked about how synaptogenesis AND enhancing efficient brain connectivity are the keys to true IQ increase imo. 

 

I didn't think it was possible back then but after reading the study linked below I think it might be a real possibility.

 

I already know how to achieve massive synaptogenesis but we now have a way to extend that synaptogenesis out to the entire brain causing efficient full brain connectivity! 

 

Read the ENTIRE study below. I'm not kidding. This could really work. Holy sh*t! This is insane. 

 

I'm going to crank synaptogenesis up to level 10 and hit my brain with a huge dose of bright light for an extended period of time. 

 

The goal is to cause massive restructuring leading to enhanced long term full brain connectivity.

 

Those of you familiar with the literature on synaptogenesis and one shot brain restructuring can probably guess one substance that will be involved. lol

 

btw, I STRONGLY urge that NO ONE do what I'm going to do. 

 

I'm a test pilot pushing the bounds of human possibility and my plane could explode.

 

I could very well end up a cautionary tale. 

 

But hey, if I go down, I'll go out in style. lol

 

Seriously though, I'll probably be fine. 

 

I've tested every substance individually already so I know how my body responds to each of them. 

 

Hell, I've tested most of them in combination already.

 

Anyway, check out this mind-blowing study below. 

 

This is crazy.

 

"BLT can enhance intra-network functional connectivity in the DMN, FPN, SN, and SMN for MDD patients. Furthermore, BLT improves the information processing of the whole brain." https://www.ncbi.nlm...les/PMC9681819/

 

"bright light therapy (BLT)"

"default mode network (DMN)"

"frontoparietal network (FPN)"

"salience network (SN)"

"sensorimotor network (SMN)"

 

" In this study, most nodes in the selected four networks demonstrate elevated betweenness centrality after the BLT. This finding suggests that the effect of BLT can improve the ability of multiple nodes in controlling the flow and integrity of information. Global efficiency is used to represent the efficiency of information transfer across all brain regions (35). The measurement of global efficiency can reflect the global interconnected status of the nodes within a network. All the nodes in these four networks demonstrate elevated global efficiency after BLT, implying that the effect of BLT can enhance the functional connection of nodes and help information flow to be more efficiently exchanged. In addition to the effect of enhancing intra-network functional connectivity of the DMN, FPN, SN, and SMN in MDD patients, based on the results of graph analysis, the BLT also helps global information processing of the brain by improving the flow and integrity of information and the efficiency of global information exchange among the nodes in these four networks."

 

 

https://www.ncbi.nlm...les/PMC9681819/

 

 

Front Neurol

 

Subclinical alterations of resting state functional brain network for adjunctive bright light therapy in nonseasonal major depressive disorder: A double blind randomized controlled trial

Chun-Chao Huang 1 2 3, Hui-Chun Huang 3 4, Chen-Ju Lin 5 6, Chien-Chi Hsu 2 5, Chau-Shoun Lee 2 5, Yu-Hsin Hsu 7, Ting-Lin Chen 1, Wei-Hsin Liao 1, Yun-Hsiang Wu 8, Fan-Pei Gloria Yang 8 9 10, Shen-Ing Liu 2 3 5

Abstract

Introduction: The treatment effect of bright light therapy (BLT) on major depressive disorder (MDD) has been proven, but the underlying mechanism remains unclear. Neuroimaging biomarkers regarding disease alterations in MDD and treatment response are rarely focused on BLT. This study aimed to identify the modulatory mechanism of BLT in MDD using resting-state functional magnetic resonance imaging (rfMRI).

Materials and methods: This double-blind, randomized controlled clinical trial included a dim red light (dRL) control group and a BLT experimental group. All participants received light therapy for 30 min every morning for 4 weeks. The assessment of the Hamilton Depression Rating Scale-24 (HAMD-24) and brain MRI exam were performed at the baseline and the 4-week endpoint. The four networks in interest, including the default mode network (DMN), frontoparietal network (FPN), salience network (SN), and sensorimotor network (SMN), were analyzed. Between-group differences of the change in these four networks were evaluated.

Results: There were 22 and 21 participants in the BLT and dRL groups, respectively. Age, sex, years of education, baseline severity, and improvement in depressive symptoms were not significantly different between the two groups. The baseline rfMRI data did not show any significant functional connectivity differences within the DMN, FPN, SN, and SMN between the two groups. Compared with the dRL group, the BTL group showed significantly increased functional connectivity after treatment within the DMN, FPN, SN, and SMN. Graph analysis of the BLT group demonstrated an enhancement of betweenness centrality and global efficiency.

Conclusion: BLT can enhance intra-network functional connectivity in the DMN, FPN, SN, and SMN for MDD patients. Furthermore, BLT improves the information processing of the whole brain.

 

Our Enhancements So Far:

 

1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Get 7 to 9 hours of sleep. Full stop. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock and enhance your ability to sleep that night. Resync your master circadian clock and enhance melatonin secretion with 30 minutes of midday bright light therapy. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/

 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/

 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/

 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

 

Our Reference Frame

 

 

 

Lostfalco's Day Frame

 

5:00am - First Light: wake up, use restroom, drink 16 to 32 ounces water, bright light lamp for 30 min

5:30am - First Hike/Bike: exercise (cardio Mon, Wed, Fri, Sun; weights Tues, Thur, Sat)

6:00am - First Bite: 12 hour eating window starts; 50% of daily calories consumed at breakfast; high protein = >30g; main staples are fiber/dextrin, kale, fatty fish/oysters, extra virgin olive oil, whole eggs, blueberries

6:00am - First Type: fiber/veggies first, then protein, then carbs (sequence eating)

6:30am - stop eating, 15 min walk (outside in the sun if possible)

6:45 am to 11:30am - no food, snacks or drinks with calories; only water

11:30am - lunch; 30% of daily calories consumed at lunch; sequence eating

12:00pm - stop eating, 15 min walk (outside in the sun if possible)

12:15pm - midday bright light lamp for 30min

12:15pm to 5:30pm - no food, snacks or drinks with calories; only water

5:30pm - dinner; 20% of daily calories consumed at dinner; sequence eating

6:00pm - stop eating; 12 hour eating window closes; no food, snacks or drinks with calories; only water until 6am the following day; 15 minute walk (outside in the sun if possible)

8:00pm - turn AC down to 67°F (19.4°C); dim lights and computer screens for the rest of the evening

10:00pm - lights out, sleeping mask, white noise or air purifier or loud fan, blackout curtains

 

 

Edited by lostfalco, 03 December 2022 - 11:34 AM.

[lostfalco]

Hello my friends! I hope your Sunday is going well. 

 

If my posts going forward for the next month or so seem a little less fun and conversational than usual please forgive me. 

 

I'm going to bear down to fundamental efficient essentiality. 

 

Before we get lost in the weeds of my Moonshot Project I want to emphasize something really quickly. 

 

I'll try to say this as succinctly as possible since I've already built a Major Depression Protocol and I'm going to communicate it properly, refine it, and show you guys the scientific evidence in the coming year: combine bright light therapy + ssri + Cognitive Behavioral Therapy + bibliotherapy (Burns' Feeling Good) + my Day Frame. I've linked Burn's Feeling Good here. https://www.lostfalco.com/books/ My Day Frame is at the end of this post and Satchin Panda's work on Circadian Biology is also linked on my books page. https://www.lostfalco.com/books/

 

Doing all of these in combination will massively increase your probability of beating Major Depressive Disorder. 

 

The three key historical, evidence-based cornerstones (therapy + ssri + bibliotherapy) will be WAY more effective when the realities of bright light therapy and Circadian Biology are accounted for. 

 

This has already been shown in dozens of studies. 

 

I'll show you guys the evidence soon and also give you guys a temporal ordering to follow.

 

For example, start with Bright Light Therapy, do for one week, if symptoms abate then keep that as stand alone treatment, if BLT alone is ineffecitve, then add SSRI to Bright Light Therapy for 3 weeks, etc. 

 

There are also other things you can simultaneously. 

 

For example, do 30 min of bright light therapy while simultaneously reading Burns, THEN go for a 30 minute walk (exercise helps depression as pretty much everyone knows) while SIMULTANEOUSLY listening to Burns on audio book, etc, etc. 

 

We can also combine this with Spaced Generation Learning to enhance the learning process and long term retention of concepts for patients studying Burns. 

 

This will greatly enhance long term remission as they can continue to review Anki flashcard indefinitely on a spaced repetition schedule. 

 

For example, instead of just reading Burns while doing bright light therapy you could 1. Read Burns AND create Anki flashcards WHILE doing Bright Light Therapy on MONDAY then, 2. Study those Anki flashcards WHILE doing Bright Light Therapy on TUESDAY, etc. 

 

You guys get the idea. 

 

It's all about what you do EVERY day and the optimal ordering of the things you do each day.

 

If you can do things simultaneously with very low risk, then do them! (ie. bright light therapy and bibliotherapy have very few risks/side effects)

 

Time is our ally.

 

I'm going to take advantage of temporal concepts such First, Next, Eventually, Always, Until, etc. to refine and modify the protocol until it helps the most people we can possibly help. 

 

I'm using Linear Temporal Logic to model these ideas and make sure my protocols take into account cardinality, ordinality, etc. in order to be as exact, concrete, and precise as possible. 

 https://en.wikipedia..._temporal_logic

 

There are also a lot of 'IF-else's' in there so I may use computational tree logic to model various scenarios for various people but I also want to keep it simple so, we'll see. https://en.wikipedia.org/wiki/CTL*

 

Clearly though, there are going to be things that just about ALL people should do ALWAYS...for example go to bed at the same time, wake up at the same time, eat at the same time, etc. 

 

Temporal Logic concepts will allow us to tease out the ALWAYS from the conditional and design a protocol that helps the greatest number of people possible. 

 

Wholistic, temporally ordered therapies like this have the best chance of long term success imo. 

 

That's coming in the next few months. 

 

I'll do my best to communicate that with the world as soon as I can. 

 

Right now, I need to enhance myself so I can be the greatest force of good possible in the coming years. 

 

So, that brings us to my Moonshot Project. 

 

This post is getting kind of long so I'm going to just briefly mention the other core substance in my Moonshot Menagerie...MDMA. 

 

I'll talk more about it later but before you freak out, read the studies below in their entirety.

 

MDMA is currently expected to be approved for treatment in 2023.

 

My purpose for including MDMA is extreme, rapid synaptogenesis. (See study below)

 

 

My primary goal is to gain conscious access to the most fundamental parts of my neural architecture (whole brain efficiency and connectivity) AND to increase connectivity and efficiency in the FPN especially (frontoparietal network). (See study in my previous post).

 

The MDMA is going to give me massive connectivity AND the bright light is going to make that connectivity as efficient as possible. 

 

The frontoparietal network includes areas and aptitudes typically included in IQ measurements (ie. sustained attention, complex problem-solving,  working memory, etc.) and increased efficiency and connectivity between nodes in this network has the potential to increase IQ.

 

So, I'm going to be strengthening the connections within single networks and then I'm going to be strengthening connections from network to network.

 

In copying the studies I'm currently leaning towards 3 doses spread out 3 weeks apart with 100mg MDMA taken first followed by 50mg MDMA taken 2 hours later for a total of 8 hours per session and 3 total sessions. 

 

I'm tentatively setting my dates for Dec 25th, Jan 14th, and Feb 4th.  

 

I'll do 8 hours each moonshot day, study my Anki flashcards the whole session if I'm able, and post here periodically (maybe every 15 minutes or half hour) while I'm dosing.

 

I'll keep you guys updated as I do more research. 

 

All things are currently flexible and open to change.

 

There are so many more substances I'm thinking about adding. 

 

Bottom line though is that I'll keep doing bright light therapy during the moonshot sessions and between the moonshot sessions since the whole brain network effects were shown after 4 weeks of daily bright light therapy in the study I linked in my last post. 

 

This pretty much perfectly aligns with the 6 week, 3 dose plan of MDMA.

 

Beautiful.

 

Ok, gotta run. So much more to share in the coming days!

 

btw, If I get shut down on Longecity in the future you guys know my website address (see links below). I'll just start posting everything over there. Peace!

 

 

https://www.ncbi.nlm...les/PMC9337778/

 

3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Therapy in Hawaii: A Brief Review

Abstract

The Food and Drug Administration (FDA) granted breakthrough therapy status to 3,4-methyl​enedioxy​methamphetamine-assisted therapy (MDMA-AT) in 2017 due to preliminary evidence supporting its efficacy and safety in treating post-traumatic stress disorder (PTSD). A series of six phase-II clinical trials studying MDMA-AT for treatment-resistant PTSD found that 54% of MDMA-AT full-dose participants no longer met the diagnosis of PTSD after two MDMA sessions, compared to 23% in the control group. In the first phase-III clinical trial, 67% no longer met the criteria for PTSD after three sessions. The effects are durable, with 67% no longer diagnosable after one year and 74% at nearly four years. The MDMA-AT is being fast-tracked for potential FDA approval by 2023. In 2021, Hawaii's Senate Bill 738 unsuccessfully proposed that psilocybin be removed from the Schedule I controlled substances list due to its clinical efficacy for major depressive disorder. Methyl​enedioxy​methamphetamine is also a Schedule I controlled substance and has proven to be a treatment option that could potentially benefit the people of Hawaii.

 

 

https://www.scienced...211124718307551

Psychedelics Promote Structural and Functional Neural Plasticity

Highlights

 

•Serotonergic psychedelics increase neuritogenesis, spinogenesis, and synaptogenesis
•Psychedelics promote plasticity via an evolutionarily conserved mechanism
•TrkB, mTOR, and 5-HT2A signaling underlie psychedelic-induced plasticity
•Noribogaine, but not ibogaine, is capable of promoting structural neural plasticity

Summary

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders.

 

 

https://www.ncbi.nlm...les/PMC9700802/

 

Towards an understanding of psychedelic-induced neuroplasticity

Abstract

Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term improvements arise because psychedelics rapidly and lastingly stimulate neuroplasticity. The focus of this review is on answering specific questions about the effects of psychedelics on neuroplasticity. Firstly, we review the evidence that psychedelics promote neuroplasticity and examine the cellular and molecular mechanisms behind the effects of different psychedelics on different aspects of neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, and expression of plasticity-related genes (e.g., brain-derived neurotrophic factor and immediate early genes). We then examine where in the brain psychedelics promote neuroplasticity, particularly discussing the prefrontal cortex and hippocampus. We also examine what doses are required to produce this effect (e.g., hallucinogenic doses vs. "microdoses"), and how long purported changes in neuroplasticity last. Finally, we discuss the likely consequences of psychedelics' effects on neuroplasticity for both patients and healthy people, and we identify important research questions that would further scientific understanding of psychedelics' effects on neuroplasticity and its potential clinical applications.

 

 

Our Enhancements So Far:

 

1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Get 7 to 9 hours of sleep. Full stop. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock and enhance your ability to sleep that night. Resync your master circadian clock and enhance melatonin secretion with 30 minutes of midday bright light therapy. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/

 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/

 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/

 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

 

Our Reference Frame

 

 

 

Lostfalco's Day Frame

 

5:00am - First Light: wake up, use restroom, drink 16 to 32 ounces water, bright light lamp for 30 min

5:30am - First Hike/Bike: exercise (cardio Mon, Wed, Fri, Sun; weights Tues, Thur, Sat)

6:00am - First Bite: 12 hour eating window starts; 50% of daily calories consumed at breakfast; high protein = >30g; main staples are fiber/dextrin, kale, fatty fish/oysters, extra virgin olive oil, whole eggs, blueberries

6:00am - First Type: fiber/veggies first, then protein, then carbs (sequence eating)

6:30am - stop eating, 15 min walk (outside in the sun if possible)

6:45 am to 11:30am - no food, snacks or drinks with calories; only water

11:30am - lunch; 30% of daily calories consumed at lunch; sequence eating

12:00pm - stop eating, 15 min walk (outside in the sun if possible)

12:15pm - midday bright light lamp for 30min

12:15pm to 5:30pm - no food, snacks or drinks with calories; only water

5:30pm - dinner; 20% of daily calories consumed at dinner; sequence eating

6:00pm - stop eating; 12 hour eating window closes; no food, snacks or drinks with calories; only water until 6am the following day; 15 minute walk (outside in the sun if possible)

8:00pm - turn AC down to 67°F (19.4°C); dim lights and computer screens for the rest of the evening

10:00pm - lights out, sleeping mask, white noise or air purifier or loud fan, blackout curtains

 

Edited by lostfalco, 05 December 2022 - 10:53 AM.

[lostfalco]

Click here to buy caffeine powder: https://www.lostfalco.com/supplements/

Click here to buy Modafinil: https://www.lostfalc...harmaceuticals/

 

Hello my friends! Welcome to Abstract Wednesday.

 

I hope you guys are as excited as I am that we have entered a new era in nootropic experimentation. 

 

I like to name things so I will very 'creatively' call it The Circadian Era. lol

 

Honestly, the recent discoveries in circadian biology have changed everything. 

 

We now have to take into account how every substance that we take affects our body's response to LIGHT hitting the retina. 

 

Additionally, we have to take into account circadian TIMING rules in our experimentation so as not to throw off our body's daily rhythms of genetic expression, hormone secretion, receptor trafficking, etc.

 

Today, however, I want to focus on light.

 

We all know that caffeine and modafinil affect wakefulness.

 

I propose that each substance affects wakefulness primarily by changing the retina's response to light, the retinohypothalamic tract's response to light AND the suprachiasmatic nucleus' response to light. 

 

The increased activity of the suprachiasmatic nucleus in response to light thereby increases orexin secretion which increases norepinephrine secretion and thereby wakefulness. 

 

Here's how it looks:

IF more dopamine, THEN more melanopsin in ipRGCs. (see study on circadian dopamine below)

IF more melanopsin, THEN greater response of ipRGCs to light.

IF greater response of ipRGCs THEN greater release of excitatory glutamate onto suprachiasmatic nucleus neurons. 

IF greater release of glutamate on to suprachiasmatic nucleus neurons, THEN greater release of glutamate onto orexin secreting neurons.

IF greater release of glutamate onto orexin secreting neurons, THEN greater orexin neuron excitation THEN enhanced wakefulness THEN enhanced locus coeruleus release of norepinephrine THEN even greater increased wakefulness. 

 

ipRGCs = intrinsically photosensitive retinal ganglion cells.

Note: exercise increases orexin production so use my Day Frame below to schedule exercise into your day to enhance this pathway further. We want to enhance orexin production AND orexin release for optimal cascading wakeful and cell synchronizing effects to our entire body. 

 

Look at our Reference Frame below to get clear on the sequence. 

 

So, caffeine increases dopamine which could increase melanopsin expression in ipRGCs. 

Modafinil increases dopamine which could also increase melanopsin expression in ipRGCs. 

Caffeine inhibits adenosine receptors on retinohypothalamic tract neurons which will increase glutamate release onto the suprachiasmatic nucleus. (see studies below)

Modafinil enhances glutamatergic signaling in the brain which could increase glutamate release onto the suprachiasmatic nucleus. (see studies below)

 

Of course, substances have MANY different effects in MANY different areas of the brain and body, but the is THE most upstream area there is. 

 

We are talking about the chromophore's (melanopsin in this case) interaction with light itself. 

 

The VERY interface of our body with photonic input from the external environment.

 

Note: ALWAYS focus on fundamental interfaces. There are always surprises here. If we change the interface then we can change EVERY downstream affect from that fundamental source. Additionally, we can control the fundamental INPUT to that interface by controlling light. It's incredible what we can do now days. We can control the input into the interface (light) AND the response of that interface (melanopsin) to the input. This has cascading affects throughout our ENTIRE body. It's crazy. We've seriously found The Grail. 

 

 

https://www.frontiersin.org/articles/10.3389/fncel.2017.00091/full

 

Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System

Abstract

Circadian rhythms are daily rhythms that regulate many biological processes - from gene transcription to behavior - and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian ("clock") genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine. Dopamine has been shown to have circadian-like activities in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it regulates, and is regulated by, clock genes in some of these areas. Thus, it is likely that dopamine is essential to mechanisms that maintain proper rhythmicity of these five brain areas. This review discusses studies that showcase different dopaminergic mechanisms that may be involved with the regulation of these brain areas' circadian rhythms. Mechanisms include how dopamine and dopamine receptor activity directly and indirectly influence clock genes and proteins, how dopamine's interactions with gap junctions influence daily neuronal excitability, and how dopamine's release and effects are gated by low- and high-pass filters. Because the dopamine neurons described in this review also release the inhibitory neurotransmitter GABA which influences clock protein expression in the retina, we discuss articles that explore how GABA may contribute to the actions of dopamine neurons on circadian rhythms. Finally, to understand how the loss of function of dopamine neurons could influence circadian rhythms, we review studies linking the neurodegenerative disease Parkinson's Disease to disruptions of circadian rhythms in these five brain areas. The purpose of this review is to summarize growing evidence that dopamine is involved in regulating circadian rhythms, either directly or indirectly, in the brain areas discussed here. An appreciation of the growing evidence of dopamine's influence on circadian rhythms may lead to new treatments including pharmacological agents directed at alleviating the various symptoms of circadian rhythm disruption.

 

 

https://onlinelibrar...68.2005.04512.x

 

Dopamine regulates melanopsin mRNA expression in intrinsically photosensitive retinal ganglion cells

Abstract

In mammals a subpopulation of retinal ganglion cells are intrinsically photosensitive (ipRGCs), express the photopigment melanopsin, and play an important role in the regulation of the nonimage-forming visual system. We have recently reported that melanopsin mRNA and protein levels in the rat retina are under photic and circadian control. The aim of the present work was to investigate the mechanisms that control melanopsin expression in the rat retina. We discovered that dopamine (DA) is involved in the regulation of melanopsin mRNA, possibly via dopamine D2 receptors that are located on these ipRGCs. Interestingly, we also discovered that pituitary adenylate cyclase-activating peptide (PACAP) mRNA levels are affected by DA. Dopamine synthesis and release in the retina are regulated by the rod and the cone photoreceptors via retinal circuitry; our new data indicate that DA controls melanopsin expression, indicating that classical photoreceptors may modulate the transcription of this new photopigment. Our study also suggests that DA may have an important role in mediating the light signals that are used for circadian entrainment and for other responses that are mediated by the nonimage-forming visual system.

 

https://www.ncbi.nlm...les/PMC2104795/

Presynaptic Adenosine A1 Receptors Regulate Retinohypothalamic Neurotransmission in the Hamster Suprachiasmatic Nucleus

Abstract

Adenosine has been implicated as a modulator of retinohypothalamic neurotransmission in the suprachiasmatic nucleus (SCN), the seat of the light-entrainable circadian clock in mammals. Intracellular recordings were made from SCN neurons in slices of hamster hypothalamus using the in situ whole-cell patch clamp method. A monosynaptic, glutamatergic, excitatory postsynaptic current (EPSC) was evoked by stimulation of the optic nerve. The EPSC was blocked by bath application of the adenosine A1 receptor agonist cyclohexyladenosine (CHA) in a dose-dependent manner with a half-maximal concentration of 1.7 µM. The block of EPSC amplitude by CHA was antagonized by concurrent application of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The adenosine A2A receptor agonist CGS21680 was ineffective in attenuating the EPSC at concentrations up to 50 µM. Trains of four consecutive stimuli at 25 ms intervals usually depressed the EPSC amplitude. However, after application of CHA, consecutive responses displayed facilitation of EPSC amplitude. The induction of facilitation by CHA suggested a presynaptic mechanism of action. After application of CHA, the frequency of spontaneous EPSCs declined substantially, while their amplitude distribution was unchanged or slightly reduced, again suggesting a mainly presynaptic site of action for CHA. Application of glutamate by brief pressure ejection evoked a long-lasting inward current that was unaffected by CHA at concentrations sufficient to reduce the evoked EPSC amplitude substantially (1 to 5 µM), suggesting that postsynaptic glutamate receptor-gated currents were unaffected by the drug. Taken together, these observations indicate that CHA inhibits optic nerve-evoked EPSCs in SCN neurons by a predominantly presynaptic mechanism.

 

https://www.ncbi.nlm...les/PMC2696807/

 

Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain: Clinical Implications

Abstract

Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise.

Objective

To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain.

Design, Setting, and Participants

Positron emission tomography with [11C]raclopride (D2/D3 radioligand sensitive to changes in endogenous dopamine) and [11C]cocaine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007–2008) at Brookhaven National Laboratory.

Main Outcome Measures

Primary outcomes were changes in dopamine D2/D3 receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo.

Results

Modafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%]; 95% confidence interval [CI], 1.5% to 10.8%; P=.02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P=.002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P=.02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P<.001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P<.001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P=.001), reflecting occupancy of dopamine transporters.

Conclusions

In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations.

https://pubmed.ncbi....h.gov/30468674/

Modafinil and orexin system: interactions and medico-legal considerations

Abstract

Modafinil (Mo) is increasingly being used as an enhancement drug rather than for its therapeutic effects. The effects of this drug have been examined in attention deficit disorders, depression, mental fatigue, and in enhancing concentration. The drug possesses wakefulness-promoting properties which are mediated through the interaction of orexinergic system with the activated sympathetic nervous system. Mo exerts a synergistic effect on the orexin system, controls energy expenditure and strengthens the ability of the individual to exercise. Some view Mo as a drug that enhances sports performance, since it induces a prolonged wakefulness and decreasing the sense of fatigue. These characteristics being similar to conventional stimulants have allowed Mo to emerge as a novel stimulant requiring medico-legal considerations. However, more studies are needed to better understand the mid and long-term effects of the drug on user/abuser.

 

https://pubmed.ncbi....h.gov/14521986/

Stimulant doses of caffeine induce c-FOS activation in orexin/hypocretin-containing neurons in rat

Abstract

Although caffeine is a commonly used CNS stimulant, neuronal mechanisms underlying its stimulatory effect are not fully understood. Orexin (hypocretin)-containing neurons play a critical role in arousal and might be activated by acute administration of caffeine. We examined this possibility by using dual-immunostaining for orexin B and c-Fos protein as a marker for neuronal activation. Rats were administered intraperitoneally with 10, 30 or 75 mg/kg caffeine, or saline. As previously reported, caffeine increased locomotion at 10 and 30 mg/kg, but not at 75 mg/kg. The numbers of orexin-immunoreactive and non-orexin-immunoreactive neurons expressing c-Fos were analysed using three counting boxes within the orexin field in the posterior hypothalamus. Compared with saline, all doses of caffeine increased the number of cells immunoreactive for both orexin and c-Fos. The average magnitude of this increase across doses in orexin neurons differed amongst regions; c-Fos expression increased by 343% in the perifornical area and by 158% in the more medial, dorsomedial nucleus. In the lateral hypothalamic area, c-Fos expression increased by 226% at 10 and 30 mg/kg but no change was seen at 75 mg/kg. In contrast, caffeine significantly increased the number of non-orexin-immunoreactive neurons expressing c-Fos only in the dorsomedial nucleus. These results indicate that systemically administered caffeine preferentially activates orexin neurons over non-orexin neurons in the same field, and that this activation is most pronounced in the perifornical region where orexin neurons are most concentrated. The activation of orexin neurons might play a role in the behavioural activation by caffeine.

 

https://pubmed.ncbi....ih.gov/9376524/

The antinarcoleptic drug modafinil increases glutamate release in thalamic areas and hippocampus

Abstract

The antinarcoleptic drug modafinil [(diphenyl-methyl)-sulfinyl-2-acetamide; Modiodal] dose-dependently inhibits the activity of GABA neurons in the cerebral cortex and in the nucleus accumbens, as well as in sleep-related brain areas such as the medial preoptic area and the posterior hypothalamus. This study examined the effects of modafinil (30-300 mg/kg, i.p.) on dialysate glutamate and GABA levels in the ventromedial (VMT) and ventrolateral (VLT) thalamus and hippocampal formation (Hip) of the awake rat. The results show a maximal increase in glutamate release in these brain regions at the 100 mg/kg dose, associated with a lack of effect on GABA release. Thus modafinil may increase excitatory glutamatergic transmission in these regions, altering the balance between glutamate and GABA transmission.

Our Enhancements So Far:

 

1. Sync Your Central Clock with Bright Light Therapy: Go to bed at the same time every day and wake up at the same time every day. Get 7 to 9 hours of sleep. Full stop. Do 30 minutes of bright light therapy first thing in the morning to sync your master circadian clock and enhance your ability to sleep that night. Resync your master circadian clock and enhance melatonin secretion with 30 minutes of midday bright light therapy. Click here for my recommended bright light device. http://www.lostfalco...re-to-buy-them/

 

2. Sync Your Microbiome Clock with Dextrin: Eat fiber at the beginning of each meal to sync your microbiome clock. Click here to try dextrin. https://www.lostfalco.com/supplements/

 

3. Sync Your Peripheral Clock with Meal Timing and Exercise Timing (Hex Bar, Pull Up Bar, Fit Desk): Eat at the same times each day within an 8 to 12 hour window and exercise for 30 min (remember the exerkines!) at the same time every day. Click here for simple, affordable devices you can use at home. https://www.lostfalco.com/devices/

 

4. Use 'Sequence Eating' to Control Glycemic Response: Eat Fiber/Veggies first THEN Protein THEN Carbs (eat fat with fiber and/or protein) https://www.lostfalco.com/supplements/

 

Our Reference Frame

 

 

 

Lostfalco's Day Frame

 

5:00am - First Light: wake up, use restroom, drink 16 to 32 ounces water, bright light lamp for 30 min

5:30am - First Hike/Bike: exercise (cardio Mon, Wed, Fri, Sun; weights Tues, Thur, Sat)

6:00am - First Bite: 12 hour eating window starts; 50% of daily calories consumed at breakfast; high protein = >30g; main staples are fiber/dextrin, kale, fatty fish/oysters, extra virgin olive oil, whole eggs, blueberries

6:00am - First Type: fiber/veggies first, then protein, then carbs (sequence eating)

6:30am - stop eating, 15 min walk (outside in the sun if possible)

6:45 am to 11:30am - no food, snacks or drinks with calories; only water

11:30am - lunch; 30% of daily calories consumed at lunch; sequence eating

12:00pm - stop eating, 15 min walk (outside in the sun if possible)

12:15pm - midday bright light lamp for 30min

12:15pm to 5:30pm - no food, snacks or drinks with calories; only water

5:30pm - dinner; 20% of daily calories consumed at dinner; sequence eating

6:00pm - stop eating; 12 hour eating window closes; no food, snacks or drinks with calories; only water until 6am the following day; 15 minute walk (outside in the sun if possible)

8:00pm - turn AC down to 67°F (19.4°C); dim lights and computer screens for the rest of the evening

10:00pm - lights out, sleeping mask, white noise or air purifier or loud fan, blackout curtains

 

Click here to buy caffeine powder: https://www.lostfalco.com/supplements/

Click here to buy Modafinil: https://www.lostfalc...harmaceuticals/

Edited by lostfalco, 08 December 2022 - 12:08 AM.

[Sikorsky]

You are a gold mine of information. Can't wait for the results of your IQ experiment. You wrote a post on your website about intranasal insulin 6 years ago. How often have you been using it since and do you still consider it to be safe long-term?

[Sikorsky]

Do you think it would be effective to incorporate into your Moonshot project a brain training consisting of 3 components - musical instrument, relational frame theory, and dual n-back and then find out all possible ways to make it more complex, to structure it with as much variety and challenge.

 

For example - musical instrument - more instruments, rather than 1 - violin and piano.

 

Relational frame theory - 4D space with as many different relations and components as possible - use time not only as a relation but also as something that makes the task more challenging - for example, I have 5 minutes to remember this 4D RFT scheme and then try to answer these questions about it. This adds a sense of urgency and makes one invest energy with far more intensity. Using time to constantly push yourself (maybe use it to be in that 4% sweet spot necessary for flow), since it is a parameter that is easiest to manipulate to create the desired magnitude of the challenge. Of course, it is only one lever, one could find a lot of creative ways of fine-tuning the magnitude of the challenge. The schemes and questions could be generated by a computer so that every time you use it for brain training, you have different objects, colors, and all other properties of these objects so that you can't remember schemes during the process of creating them, which would make the task easier, but rather every time you would see a unique, novel scheme.  

 

Dual n-back - There are all sorts of ways one could make it more complex - add variety and challenge. One of the most obvious ones would be to make it 3D. I think it wouldn't be hard to come up with a lot of creative ways to make it more complex (and therefore to make bigger gains since I presume gains are proportional to complexity and amount and intensity of energy one is investing).

 

I am very curious about the substances you are planning to stack. Nicotine? I presume you are also thinking about substances that would raise your capacity for energy output (amount, intensity) during that window of opportunity since gains are proportional to that.

[lostfalco]

You are a gold mine of information. Can't wait for the results of your IQ experiment. You wrote a post on your website about intranasal insulin 6 years ago. How often have you been using it since and do you still consider it to be safe long-term?

Thanks Sikorsky! I read a little too much. lol

 

I used intranasal insulin for 1 year straight in 2016 and stopped because there was no data on long term usage in humans. 

 

It noticeably increased my mood but I didn't notice any memory enhancement from it so I moved on. 

 

I haven't had any negative effects from it at all...either short term or long term. 

 

As far as long term safety...I haven't dug deeply into the recent data because I've obviously been distracted by my current Circadian obsession so I'll have to let you know my view on long term safety once I look at the most recent studies.

 

I did look long enough to determine that it wasn't a priority to focus on in the retina, retinohypothalamic tract, and suprachiasmatic nucleus. 

 

I'll let you know once I dig back into the data. It's still a fascinating substance. 

Edited by lostfalco, 12 December 2022 - 01:00 AM.

[lostfalco]

 

Do you think it would be effective to incorporate into your Moonshot project a brain training consisting of 3 components - musical instrument, relational frame theory, and dual n-back and then find out all possible ways to make it more complex, to structure it with as much variety and challenge.

I totally thought of you when I read that fMRI study on how bright light therapy enhances whole brain connectivity and efficiency. lol

 

This is EXACTLY what you asked about a few months ago. 

 

All of your suggestions are excellent and I'm considering them all. 

 

One thing to remember though is that my whole 6 week 'Moonshot Cycle' is going to consist of three individual 'Moonshot Sessions' that will be 8 hours each of bright light plus MDMA (as core substances; and of course, not bright light the entire 8 hours. ha).

 

Given my love of incrementalism I'm going to ease into the first 8 hour moonshot session and not go too crazy on the substances or the training during the 8 hours. 

 

I'll keep the substances somewhat minimal, study a huge range of flashcards the whole time (if I can. lol), go for walks in the sunlight, etc. 

 

I need to see how MDMA plus bright light is going to affect me at that dose in order to determine how I will approach the next two 8 hour sessions. 

 

I've already tested a pilot dose of 25mg MDMA plus 30min bright light and it was awesome. 

 

So, I'm good to go for the full dose plus bright light on December 26th. (I bumped it later by a day from December 25th)

 

The other two Moonshot Sessions will be on the same days as originally stated: Jan 14th and Feb 4th.  

 

In between sessions I'm going to make sure my diet and Circadian daily rhythm are as flawless as I can make them. 

 

I'll stick to my Day Frame as religiously as I can to keep my Brain, Body, and Biome as synced up as humanly possible. 

 

As far as additional substances, I'm pretty sure the following are going to make the cut: caffeine (due to adenosine inhibition), testosterone enanthate at a high end trt dose (estrogen, testosterone, and dht enhance synaptogenesis), and sermorelin at night due to growth hormone and IGF-1 increases (IGF-1 in particular shows synaptogenesis increases).

 

I'll try to be as Circadian as I can be with the testosterone but it has a long half-life and I don't have access to Natesto (nasal testosterone; it's a particularly interesting circadian substance due to it's short half life). 

 

Nicotine is probably not going to make the cut for this first session because MDMA increases acetylcholine release already and I don't think it's necessary to toggle that switch upward. (see study below)

 

Modafinil is in the same boat since I should be getting plenty of dopamine flooding the brain and I don't think additional reuptake inhibition makes sense. 

 

Adderall and Ritalin are out for similar reasons. 

 

There are hundreds of other substances I'm considering but I keep returning to my own mantra: Simplicity. 

 

MDMA releases such a wide range of neuromodulators that it may not require much more than bright light therapy to have incredible effects. 

 

I may change my mind after the first session but for now, that's the plan. 

 

I'll be more specific about dosages and combinations in the coming week or two. 

 

Only two weeks left. The countdown is on!

 

https://www.ncbi.nlm...les/PMC2505334/

 

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

Absract

3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative and a popular drug of abuse that exhibits mild hallucinogenic and rewarding properties and engenders feelings of connectedness and openness. The unique psychopharmacological profile of this drug of abuse most likely is derived from the property of MDMA to promote the release of dopamine and serotonin (5-HT) in multiple brain regions. The present review highlights primarily data from studies employing in vivo microdialysis that detail the actions of MDMA on the release of these neurotransmitters. Data from in vivo microdialysis experiments indicate that MDMA, like most amphetamine derivatives, increases the release of dopamine in the striatum, n. accumbens and prefrontal cortex. However, the release of dopamine evoked by MDMA in each of these brain regions appears to be modulated by concomitantly released 5-HT and the subsequent activation of 5-HT2A/C or 5-HT2B/C receptors. In addition to its stimulatory effect on the release of monoamines, MDMA also enhances the release of acetylcholine in the striatum, hippocampus and prefrontal cortex, and this cholinergic response appears to be secondary to the activation of histaminergic, dopaminergic and/or serotonergic receptors. Beyond the acute stimulatory effect of MDMA on neurotransmitter release, MDMA also increases the extracellular concentration of energy substrates, e.g., glucose and lactate in the brain. In contrast to the acute stimulatory actions of MDMA on the release of monoamines and acetylcholine, the repeated administration of high doses of MDMA is thought to result in a selective neurotoxicity to 5-HT axon terminals in the rat. Additional studies are reviewed that focus on the alterations in neurotransmitter responses to pharmacological and physiological stimuli that accompany MDMA-induced 5-HT neurotoxicity.

 

Edited by lostfalco, 12 December 2022 - 01:54 AM.

[lostfalco]

For my weekend post, see my short discussion of the Frontoparietal Network here: https://www.lostfalc...al-network-fpn/

 

I've started moving all of my Longecity posts over to my website and it's a sh*tshow right now but I'll get everything cleaned up and organized for you guys in the coming weeks. 

 

I have this massive cathedral of interconnected ideas in my head and I need to just start posting individual nodes one at a time so that I can incrementally connect each node for you guys in the coming weeks and months. 

 

My Day Frame is here: https://www.lostfalc...lcos-day-frame/

 

Feynman and the Bird is here: https://www.lostfalc...d-by-lostfalco/

 

Spaced Generation Learning is here (it's a mess right now!): https://www.lostfalc...g-by-lostfalco/

 

Sequence Eating is here: https://www.lostfalc...g-by-lostfalco/

 

Exerkines are here: https://www.lostfalco.com/exerkines/

 

My Guiding Principles are here: https://www.lostfalc...ing-principles/

 

Psychoplastogens + Bright Light Therapy is here: https://www.lostfalc...hange-humanity/

 

The summary of our enhancements of Central, Peripheral, and Biome clocks are here: https://www.lostfalc...cements-so-far/

 

Our reference frame is here: https://www.lostfalc...eference-frame/

 

I have literally thousands of posts in progress and I have some crazy stuff to show you guys (the retina is ridiculously Circadian! Everything starts there with the interface between us and light. It's beautiful. I'll show you guys soon.). 

 

It's just going to take a little time to clean it, refine it, order it, and synthesize it into the most optimal protocol based on the latest and greatest science. 

 

We'll get there. 

 

Step by step, piece by incremental piece. 

 

2023 is going to be off the charts my friends. 

 

Get ready. 

 

Most importantly though...never forget the simple things. 

 

Temporally order your life around the rotation of the Earth. 

 

Sleep 7 to 9 hours and wake at the same time every day, get sunlight on your body and eyes at the same time every day, eat at the same times every day, exercise at the same time every day, eat fiber first, then protein, then veggies. 

 

All that stuff is free!

 

Sync your Brain, Body, and Biome incrementally over time. 

 

Genius is not mania. 

 

Genius is perfect synchrony between all 68 trillion cells of the superorganism that is you.

 

Time is the most fundamental substance. 

 

Synchrony is the optimal ordering of that substance.

 

Use it to create the life you've always dreamed of. 

 

We're gonna do this my friends. 

 

It's already happened. 

 

This is real. 

 

Sh*t's gonna be crazy. 

 

LF Out.

Edited by lostfalco, 12 December 2022 - 01:56 AM.

[Q did it!]

I've been checking in and reading along LostFalco! Hope the iq increase works. U should look into 40 years of zen too