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“When one realizes one is asleep, at that moment one is already half-awake.”
― P.D. Ouspensky

Updated: Sept/11/2014……work in progress

#lupus humor www.mollysfund.org

See my protocol for curing fatigue.

1) Lactate

I spoke about using lactate as a backup generator before.

Researchers  found that lactate causes cells in the brain to release more noradrenaline (norepinephrine in US English), a hormone and neurotransmitter which is fundamental for brain function. Without it, people can hardly wake up or focus on anything. (R)

Production of lactate can be triggered by muscle use, which reinforces the connection between exercise and positive mental wellbeing………In the brain, it has always been regarded as an energy source which can be delivered to neurons as fuel to keep them working when brain activity increases. (R)

Lactate is also a critical energy source and a regulator of the orexin system. Lactate release from astrocytes  plays an integral part in balancing brain activity and energy supply. (R)

Supplying orexin neurons with lactate and can stop glucose from blocking orexin neurons (R).

Lactate is the most powerful and abundant in my experience.

The effect of lactate on firing activity is concentration dependent. Also, lactate disinhibits and sensitizes these orexin neurons for future excitation (R).

One study hypothesized that orexin neurons only ‘see’ glucose changes when the levels of other energy molecules are low, whereas high energy levels can stop glucose from regulating orexin cells (R).

Read my post about lactate and orexin.

I use this Kombucha Scoby to produce my own.  I use random, cheap decaf teas.

I do interval exercise as well.  Exercise has an added benefit of increasing cAMP.

2) Resistant Starch

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This you will only feel the next day, but it does have a wakeful promoting effect, but again use it the day before.

Hi-Maize  produces butyrate, which is an energy-related molecule and should, therefore, block glucose-induced suppression of orexin (R). Also, butyric acid is acidic and therefore may also increase orexin in that manner.

I’ve found that it does indeed increase wakefulness after a glucose challenge or a big meal.

As discussed above, it also is a GLP-1 agonist, so it can increase orexin and therefore wakefulness in multiple ways,

This is on top of the fact that it can improve memory via BDNF (R) and longevity.

I use Hi-Maize  resistant starch, to great effect.

3) Bright light

This you will feel instantly.  It wakes you up like no body’s business.

Bright light is used for seasonal affective disorder (SAD) and depression.

It’s been known to increase BDNF, but recently it’s been demonstrated that it increases orexin and that’s the likely mechanism by which it’s effective for SAD (R).

4) Breath All The Way Out

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Take a deep breath in and then breath out all of the ways.   The key here is to breath out to the point that it almost hurts.   When you breathe out try to breath out even more.

This is a breathing technique I use to wake me up if need be.

5) Stimulating Breath

6) Fructose/Honey/Fructans

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Fructose, Fructans, and FOS excite orexin neurons by increasing GLP-1, thereby increasing wakefulness (RR2).

Studies have found that long-term fructose consumption (bingeing)  increases orexin (R).  Also, 25% of fructose consumed turns into lactate, which blocks orexin suppression by glucose (R).

Heavy fructose consumption may not be the most healthy way to increase orexin, but based on my experience, it’s effective.

Raw honey is my preferred source.

7) Take a walk

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Walking wakes me up.  Perhaps a long walk is stimulating  by increasing BDNF in the hippocampus (R)

8) C60

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C60 is the most powerful anti-oxidant that I have ever taken and it’s the most long lasting as well. This gives me a nice steady mitochondrial boost throughout the day.

Fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a likely biological mechanism for fatigue (R). ROS/Oxidative stress increases TNF (R), which may explain why anti-oxidants can help.

9) PQQ

PQQ is a powerful mitochondrial enhancer and is stimulating.   It creates new mitochondria and acts as an antioxidant, which may explain why it promotes wakefulness.

10) Rhodiola

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This is very good.  Rhodiola specifically increases dopamine and noradrenaline  in the hypothalamus, which makes us more awake (R– in the body of the study.)

I don’t take this anymore because it increases the immune system and gave me some inflammation.

11) Jasmine Tea

This is the best tea with regard to waking me up.  I think it has to do with caffeine and increasing thyroid hormones (tea suppresses iodine uptake, which causes some of us to increase thyroid hormone release).

12) Yerba Mate

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Yerba mate has caffeine and other xanthines but is more gentle than coffee.

I’m much less allergic to this than coffee.

13) Longvida Curcumin, Boswellia,  Grapeseed extract

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Curcumin probably works by inhibiting TNF, as do the others.

I use these: BoswelliaCurcuminGrape Seed Extract.

14) Nicotine

15) Caffeine

16) Suma

I don’t know the mechanism as there’s no science on it, but it feels like a mitochondrial booster.

17) Gotu Kola

I don’t know the mechanism as there’s no science on it, but it feels like a mitochondrial booster.  It wakes me up when I’m tired and relaxes me when I’m awake.  It’s one of the few balancing supplements for me.

18) Gynostemma

Gynostemma has strong antioxidant effects that extended to the mitochondria of cells (R).   I found that it does feel like a mitochondrial booster when I tried it.

19) Ginkgo

Ginkgo is a GABA and glycine receptor antagonists (R).   This blocks the effects of GABA and glycine, which are inhibitory neurotransmitters.

20) Adrenal glandular

The adrenal glands contain cortisol and norepinephrine.  Cortisol suppresses inflammation (TNF, IL-1b), which is what makes us fatigued.

21) Nicotinamide Riboside

To me, this feels similar as to when I take caffeine, without the negatives.  I’m more motivated and I feel I need to move about, exercise and get stuff done.

Nice performance enhancer.  NAD inhibits TNF.

22) Forskolin

This works by increasing cAMP and thyroid hormones.  Forskolin is a powerful substance and should be used with care.  I don’t recommend this to most people.

23) Water

Don’t know how this works.

24) Rosemary Essential Oil

This oil has terpenes that inhibit the enzyme acetylcholinesterase and can also increase wakefulness. This is a nootropic (R).

Rub a little next to your nose: Rosemary essential oil.

25) Chili or Cayenne pepper

These do a pretty good job at waking me up, albeit only temporarily.

26) Vegetable Juice

This functions as an antioxidant, mitochondrial booster and increases thyroid hormones in me (by blocking iodine uptake).

Containing: romaine lettuce, celery, and cucumber.  Has a very refreshing effect.

27) Cinnamon Sticks

These are hard to chew but they do wake up me pretty powerfully.  I buy them by the pound.

Probably works by inhibiting TNF.

 28) L-Dopa

L-dopa increases dopamine, which is important for mental alertness.  If you see the picture below, you’ll see that this is a mechanism of action for amphetamines.

A study  examined the ability of dopamine agonists to activate orexin neurons in the rat.  The study found that both D1 and D2 agonists are sufficient to activate orexin neurons. (R)

Antipsychotics block dopamine pathways (R) and as you might guess a side effect is fatigue.

Dopamine also converts to epinephrine, which increases alertness.

29) Alpha-GPC

Alpha GPC is a supplement that increases acetylcholine, which increases vigilance.

The disease myasthenia gravis, characterized by muscle weakness and fatigue, occurs when the body inappropriately produces antibodies against acetylcholine nicotinic receptors, and thus inhibits proper acetylcholine signal transmission.

This is a good example that demonstrates the role of acetylcholine in vigilance.

30) Acetyl-L-Carnitine

Acetyl-L-Carnitine has the acetyl portion, which increases acetylcholine.  Carnitine increases fatty acid burning and mitochondrial health.  Buy disposing and using fatty acids for energy, we get an energy boost.  This is a must if you eat a high fat diet.

31) Having Fun

A study found having fun or play was able to increase orexin, while the same level of exercise wasn’t able to (R).

The study concludes that motor and cardiovascular changes are not sufficient to elevate orexin, so they hypothesize that the emotional aspects of yard play account for the observed increase in orexin (R).

32) Nucleotides

Nucleotide supplements are mostly stimulating but also have a sedating side.

Supplemental nucleotides contain 4 “ribonucleotides”: Cytidine Monophosphate (CMP), Uridine Monophosphate (UMP), Adenosine Monophosphate (AMP) and Guanosine Monophosphate (GMP).

Nucleotides are the building blocks for DNA synthesis, though I’m not sure exactly which aspect of the supplement accounts for the simulation.

UMP is more relaxing and I occasionally take it at night before bed.  This doesn’t cause the wakefulness in nucleotide supplements.

AMP contains adenosine, which is a drug used to induce sleep.  This is probably what accounts for the tiredness I feel in the mix of mostly stimulation.

33) Gum

Chewing gum improves some aspects of memory in healthy people (R).

It activates histamine H1 receptors (R), which increase wakefulness.

Gum also increases CCK release, which can be stimulating for some or fatiguing for others.

34) ICES

See my post on ICES.

Images

A pharmacodynamic model of amphetamine and TAAR1

As usual, all links going to amazon I get a small commission off of. I don’t get any commission from links going to other sites

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7 COMMENTS

  • Frederik Emil Hanfgarn

    Would you suggest that one would supplement with some anti-oxidants like NAC etc when using E-Cigarettes. Reason for me asking this, is this article I was reading from Wired:

    http://www.wired.co.uk/news/archive/2015-05/18/electronic-cigarette-liquids-bad-for-you

    So apparently there is some evidence of harm in-vitro, but I am on the fence about extrapolating those findings to an actual human, not just the tissue in a petri dish.

  • Mike

    Did you try hot water + cayenne pepper?

    According to Food Babe, “Combining cayenne with lemon increases the detoxing effect and raises the temperature of your body increasing your metabolism.”

    http://foodbabe.com/2011/12/27/habits-for-the-new-year-and-beyond-1-drink-lemon-water/

    1. Mike

      i meant hot water + lemon + cayenne pepper

  • Judd Crane

    How often would you recommend C60 usage? (Assuming no other mito enhancers than excercise nor NAC)

    Thank you!

  • Paul

    LDN is bought illegally here?

  • Joanna

    Thank you for this list. Interesting that you have put nicotine here since it is almost always regarded as “toxic” and has a generally negative stigma. I will be pulling out my e-cig again to test.

    Will taking fructose/honey on its own not trigger a hypoglycemic response?

    1. Joe

      nope

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