Ground control to Major Tom…

We’re jet-lagged, again….

If you fly with any regularity, you very likely know the feeling of being jet-lagged. 

The so-called “jet lag syndrome” includes a variety of symptoms like sleepiness, headache, body pain, fatigue, dry or irritated skin, brain fog, gastrointestinal issues, and more. 

The biological causes of jet lag are usually a combination of traveling across different time zones, breathing air lower in oxygen for several hours, exposing our bodies to more oxidative stress, dehydration caused by an environment with low-to-no humidity on the plane, limited movement, and exposure to cosmic radiation as well as airborne infectious pathogens. 

Fortunately, there are many ways to reduce these negative effects and we are going to share some of these hacks with you along with our first-ever methylene blue protocol for flying. 

But first, let’s start by understanding what happens when we get on a plane.

Airplane Travel and Oxygen Availability

Airplanes typically fly at 30,000 or 40,000 feet above sea level. The air inside the cabin is pressurized to 8,000 feet above sea level in most airplanes or 6,000 feet in Dreamliners. 

This means that we spend many hours not only flying across various time zones that disrupt our circadian rhythm, but also breathing in air that (at best) we would be breathing on an 8,000- or 6,000-foot mountain. 

The most abundant gas in the air is nitrogen, which at sea level makes up about 78% of the air we breathe. Oxygen is the second most abundant gas at about 21%. When flying, pressurized oxygen concentrations range between 15.2% (8,000 ft) and 17.6% (6,000 ft) in the airplane cabin. This doesn’t mean that there is less oxygen per se, however, since the overall cabin pressure is lower (approximately 564-609 mmHg), the partial pressure of oxygen is lower too (118-128 mmHg vs. 760 mmHg at sea level), thus decreasing the effective amount of oxygen getting into the body.

While symptoms of altitude sickness only start above 10,000 feet, lower oxygen pressure on planes decreases oxygen saturation by approximately 4% and can trigger noticeable discomfort after 3 to 9 hours, including more fatigue and brain fog, especially for those used to being at sea level.

This might not sound like a huge oxygen difference, but for our finely tuned systems, this slight decrease in oxygen pressure means much less oxygen reaching the mitochondria to produce energy and our mitochondria having to work much harder to maintain energy production levels [1,2]. 

This is especially troublesome in people that are already under mitochondrial stress (i.e., chronic inflammation, autoimmunity, infection, post viral symptoms, etc.).

In various studies on this topic, oxygen saturation is significantly reduced in all passengers traveling long and short-haul flights from 97% to 93%. Again, this might not seem like a huge decrease, but these values would potentially prompt physicians to administer supplemental oxygen to hospitalized patients [4]. 

In addition, unless you have the luxury of flying first class and have a bed available (ah, wouldn’t that be nice!), circulation of oxygenated blood decreases as we spend many hours sitting or laying “down-ish." Blood flow increases to the legs but decreases to the heart and brain. Pumping the blood upwards through our body against gravity requires higher energy and oxygen consumption as well. 

And if that wasn’t enough, the air on the plane also has low-to-no humidity, dehydrating you. Travelers might experience dry mouth and skin as well as dizziness and headaches.

And, even with good air recirculation, breathing the same air as 300 or even 800 people in an enclosed space can increase exposure to toxins and pathogens. Plus, cabin air can be mixed with engine air, which is quite toxic [5].

A few more things about travel you need to know

For example… Did you know that cosmic radiation from airplane travel is linked to cancer? Pilots and cabin crew members have an increased incidence of skin cancer due to cosmic and UV radiation [6]. Crazy, right?

Also, did you know that hypoxia (low oxygen levels) can produce glucose spikes, which can lead to insulin resistance? 

And there is more… 

The most susceptible tissues to become resistant to insulin due to hypoxia are fat tissue, as hypoxia creates an insulin-resistant state in adipocytes (fat cells) by inhibiting the phosphorylation of the insulin receptor tyrosine, decreasing glucose transport [7].

Moreover, our permanent residents in the gut, the gut microbiota, also suffer from traveling across time zones. A phenomenon called "chronodisruption" (messing up your biological clock) has a strong effect on our gut microbiota. The changes in our eating patterns during travel alter the rhythmicity of short-chain fatty acids (SCFAs), which regulate gut function on an epigenetic level [8].

And if that was not enough, the junk lighting on planes is constantly activating our sympathetic nervous system and leaving us in a constant state of alertness or fight-or-flight (LOL) mode. Even if we cover our eyes with a sleep mask, there is some evidence that cells all over our body are being stimulated by this bright light in various ways. 

Low Oxygen, Mitochondria, and Methylene Blue

If you follow our blog, you already know that mitochondria have a central role in energy production. You probably also know that when we give methylene blue to our mitochondria, it will donate electrons to the electron transport chain (ETC), which is directly involved in oxygen consumption, energy production, and cell metabolism [9]. 

And if you’re down to get nerdy… here’s a quick recap of the process: In low concentrations, methylene blue increases mitochondrial respiration by enhancing the shuttling of electrons between ETC protein complexes in the mitochondrial matrix (specifically complexes III and IV). The final electron acceptor is oxygen, which is reduced to water in a reaction catalyzed by complex IV, which is coupled with the synthesis of ATP [10].

Energy production by the mitochondrial ETC can be triggered by low oxygen levels (hypoxia). Cells exposed to hypoxia respond quickly by releasing regulatory factors, but if low oxygen levels are maintained, cells activate adaptive mechanisms. The master switch is hypoxia-inducible factor 1 (HIF-1), which is strictly bound to mitochondrial function and tightly related to oxygen levels. Therefore, under low oxygen conditions, mitochondria act as oxygen sensors and contribute to cell redox potential, ion homeostasis, and energy production [11].

In this scenario (i.e., hypoxia), methylene blue can optimize the energy production process in the mitochondria by donating electrons to the ETC independently of the amount of oxygen present. More on this is below! 

Methylene Blue May Reduce Jet Lag

Methylene blue improves mitochondrial function independent of oxygen availability

Methylene blue does this in several ways. 

As mentioned above, methylene blue donates electrons to the ETC and increases ATP production. This effect can occur both in the presence or absence of oxygen. 

Methylene blue also induces the production of the cytochrome oxidase gene and enhances the function of the cytochrome oxidase complex (complex IV), making it work faster and more efficiently. This leads to increased ATP production, especially in the most metabolically active cells like the brain cells, and can potentially help with jet lag-related brain fog [12].

In addition, when we fly, it’s harder for oxygen to attach to the red blood cells because (a) there is less available and (b) the shifting of what is known as the oxygen dissociation curve. This curve represents the amount of oxygen bound to a red blood cell at a given oxygen partial pressure and how much is released in the peripheral tissue.

But there’s more good news for methylene blue: In red blood cells, low-dose methylene blue changes the configuration of the iron (heme) in hemoglobin, the molecule that carries oxygen. This improves the oxygen-carrying capacity of hemoglobin from the lungs to every cell in the body and helps the mitochondria maintain energy production levels despite the hypoxic conditions of flying [13].

Methylene Blue Reduces Oxidative Stress

Oxidative stress is one of the major causes of aging. Low-dose methylene blue works as a powerful mitochondrial-targeting antioxidant as it scavenges the mitochondria and cytosol for free electrons (also called free radicals or oxidative molecules) to neutralize them. 

Compared with other antioxidants such as N-acetyl-L-cysteine (NAC), MitoQ, and mitoTEMPO (mTEM), methylene blue was more effective in stimulating skin fibroblast proliferation and delaying cellular aging, promoting wound healing, and increasing skin hydration and thickness [14,15]. 

Long story short: Under hypoxic conditions, we produce more free radicals (i.e., more inflammation) and methylene blue can help neutralize them. 

Methylene Blue May Decrease the Risk of Infections

There is scientific evidence dating as early as the 1940s showing the power of methylene blue as an antimicrobial (against bacteria, viruses, and parasites). Even in the current era of ever-growing antibiotic resistance, methylene blue is widely used across the world to treat even the most resistant bacteria. 

One example of many is antimicrobial photodynamic therapy (aPDT), based on a light treatment, which has shown to be as efficient as conventional antibiotics, even against antibiotic-resistant bacteria. The activity of aPDT is based on the cytotoxic effect of reactive oxygen species (ROS) with the help of substances such as methylene blue as a photosensitizer to increase oxygen levels [16].

Methylene blue has also been studied (pre-pandemic) as an effective treatment against coronaviruses when combined with certain spectrums of light [18].

Although there is no data yet on using methylene blue as prophylaxis against infections, methylene blue enhances immune system function and decreases inflammation, thus likely decreasing your susceptibility. 

Methylene Blue Reduces the Damaging Effects of Cosmic and UV Radiation

As previously mentioned, the cosmic and UV radiation that we are exposed to when we fly produces oxidative stress (mediated by ROS), which methylene blue can help neutralize. 

Methylene blue not only absorbs UVA and UVB radiation, but also helps repair the DNA damage caused by UV irradiation. As you know, methylene blue is a potent antioxidant that combats ROS-induced cellular aging in human skin, reduces DNA damage caused by UV irradiation, and prevents cell death. Methylene blue can even help prevent UVB-induced DNA damage and improve the clearance of UVA-induced cellular ROS [17]. 

Tips to Avoid Jet Lag

So… now to take action! Here are some tips you can incorporate to avoid (or at least reduce) jet lag:

• Take methylene blue before, during, and after your flight. Find the full suggested protocol below!
• With less humidity on the plane, you will already feel more dehydrated than usual. In addition, alcohol dehydrates the body even more. So, avoid alcohol and drink water — either mineral water or water with electrolytes is best. 
• Walk around and stretch as much as you can to increase blood circulation and wear compression socks to reduce the amount of blood flow pooling in your legs.
• Get oxygenated as soon as you can upon arrival. You may want to consider investing in a portable oxygen concentrator or find a local oxygen bar (yes, that’s a thing!). Hyperbaric oxygen treatment has also been used as a powerful jet lag remedy.
• Exercise when you get off the plane. This will help your body pump more oxygenated blood to all your cells and help with a faster recovery.
• Switch to the new time zone as soon as you get on the plane. Adjust your eating times, sleeping times, and light exposure accordingly!
• Speaking of light… play with your light exposure. For example, if your destination is daytime, use a bright light-mimicking device (many of them on the market) on the plane to trigger cortisol release and tell your body it’s daytime or expose yourself to sunlight upon arrival (if possible). On the contrary, if it’s nighttime at your destination, avoid the light on the plane with blue-blocking glasses. 
• Try a sleep stack of supplements before your desired “nighttime.” Or you can also try Tro Calm and be one-and-done. 
• Try intermittent fasting on the plane. Sounds hard to accomplish, but definitely worth it in the long term. 
• Consider taking digestive enzymes and probiotics to help your GI tract adapt faster to your new feeding schedule.
• Use EMF protection. There are some fancy (although expensive) shirts, caps, or blankets now on the market. 
• Try grounding by walking barefoot on the ground upon arrival or even invest in a grounding blanket to take with you on the plane. Similar to what happens in your sockets, grounding helps your body get rid of the unnecessary electrical charge your body produced during the flight, mainly through oxidative stress (but much less of an issue if you are taking methylene blue… wink!).
• Blue Cannatine can also help you be more awake and alert upon arrival. True story: Dr. Ted initially created Blue Cannatine specifically for this purpose! 
• And, for those who fear flying, Tro Calm can do the trick!

Of course, there is much more you can do too. 

If you’re curious about some state-of-the-art biohacks for jet lag including hormone optimization, check out this podcast with Ben Greenfield and Ted Achacoso talking about the “Rolls Royce” of jet lag hacking. 

Methylene Blue for Jet Lag Protocol

Over the last few years, we have tested several protocols with members of the Tro Team and our most dedicated users. 

What follows is what works the best so far.

However! It is still a work in progress so please use it as a general guide rather than a prescriptive one.

And the usual caveats apply with the use of methylene blue (i.e., the contraindications, your individual response may vary, etc.). 

Note that it’s okay to swallow the troches for this protocol rather than use them as buccal troches. However, some users report they do feel better on arrival if they use them buccally. 

Protocol:

Step 1: 4 hours before you fly, take 1 full Just Blue troche.

Step 2: Follow the instructions below for the time zone you are traveling to, not the one you are leaving. 

1. Take a full Just Blue at 8 am 
2. Take ¾ Just Blue at 12 pm 
3. Take ½ Just Blue at 5 pm 
4. Take ¼ Just Blue at 9 pm 

So for example, let’s say you have a flight at 10 am, which is 5 pm at your destination:

• Take your first full Just Blue 4 hours before (6 am).
• Then take your 5 pm dose when you get on the plane (½).
• Then, if you are still on the plane at 9 pm at your destination, take ¼.
• The following day post-travel, go back to your usual dose of Just Blue and stay on it daily for 3 to 5 days. If you don’t have a regular dose, start with ½ troche.
• If you are traveling to altitude from sea level, consider taking higher strength than usual, i.e., if you typically take ½ troche, take a full one instead for the days at altitude. We have had several reports that this is game-changing. 

Remember, watch your source of methylene blue. Make sure it’s pharmaceutical grade with USP designation. 

At Troscriptions, we take another full step and call ours Beyond USP because it is third-party tested and USP for our manufacturer, and we test it again to ensure potency and purity.

Pick up some Just Blue now and be ready for your next flight. 

Pick up some Blue Cannatine now to rip off the jet lag cobwebs once you land.

And pick up some Tro Calm to help you get some rest on the flight or quelch any fears of getting on the plane in their tracks. 

References

[1] Aldrette JA, Aldrette LE. Oxygen concentrations in commercial aircraft flights - PubMed. Southern Medical Journal 1983;76.
[2] Hinkelbein J, Schmitz J, Glaser E. Pressure but not the fraction of oxygen is altered in the aircraft cabin. Anaesthesia and Intensive Care 2019;47:209–209. https://doi.org/10.1177/0310057x19840038.
[3] Muhm JM, Rock PB, McMullin DL, Jones SP, Lu IL, Eilers KD, et al. Effect of aircraft-cabin altitude on passenger discomfort - PubMed. The New England Journal of Medicine 2007;357. https://doi.org/10.1056/NEJMoa062770.
[4] Humphreys S, Deyermond R, Bali I, Stevenson M, Fee JPH. The effect of high altitude commercial air travel on oxygen saturation - PubMed. Anaesthesia 2005;60. https://doi.org/10.1111/j.1365-2044.2005.04124.x.
[5] Brundrett G. Comfort and health in commercial aircraft: a literature review - PubMed. The Journal of the Royal Society for the Promotion of Health 2001;121. https://doi.org/10.1177/146642400112100108.
[6] Trolio RD, Lorenzo GD, Fumo B, Ascierto PA. Cosmic radiation and cancer: is there a link? - PubMed. Future Oncology (London, England) 2015;11. https://doi.org/10.2217/fon.15.29.
[7] Regazzetti C, Peraldi P, Grémeaux T, Najem-Lendom R, Ben-Sahra I, Cormont M, et al. Hypoxia Decreases Insulin Signaling Pathways in Adipocytes. Diabetes 2009;58. https://doi.org/10.2337/db08-0457.
[8] Desmet L, Thijs T, Segers A, Verbeke K, Depoortere I. Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice - PubMed. Acta Physiologica (Oxford, England) 2021;233. https://doi.org/10.1111/apha.13703.
[9] Gonzalez-Lima F, Auchter A. Protection against neurodegeneration with low-dose methylene blue and near-infrared light. Frontiers in Cellular Neuroscience n.d.;9. https://doi.org/10.3389/fncel.2015.00179.
[10] Tucker, Lu, Zhang. From Mitochondrial Function to Neuroprotection—an Emerging Role for Methylene Blue. Molecular Neurobiology 2017;55:5137–53. https://doi.org/10.1007/s12035-017-0712-2.
[11] Hypoxia and mitochondrial oxidative metabolism. Biochimica et Biophysica Acta (BBA) - Bioenergetics n.d.;1797:1171–7. https://doi.org/10.1016/j.bbabio.2010.02.011.
[12] Callaway NL, Riha PD, Bruchey AK, Munshi Z, Gonzalez-Lima F. Methylene blue improves brain oxidative metabolism and memory retention in rats - PubMed. Pharmacology, Biochemistry, and Behavior 2004;77. https://doi.org/10.1016/j.pbb.2003.10.007.
[13] Smith RP, Thron CD. Hemoglobin, methylene blue and oxygen interactions in human red cells - PubMed. The Journal of Pharmacology and Experimental Therapeutics 1972;183.
[14] Zhang X, Rojas JC, Gonzalez-Lima F. Methylene blue prevents neurodegeneration caused by rotenone in the retina - PubMed. Neurotoxicity Research 2006;9. https://doi.org/10.1007/BF03033307.
[15] Xiong, O’Donovan, Sun, Choi, Ren, Cao. Anti-Aging Potentials of Methylene Blue for Human Skin Longevity. Scientific Reports 2017;7:1–12. https://doi.org/10.1038/s41598-017-02419-3.
[16] Boltes Cecatto R, Siqueira de Magalhães L, Fernanda Setúbal Destro Rodrigues M, Pavani C, Lino-dos-Santos-Franco A, Teixeira Gomes M, et al. Methylene blue mediated antimicrobial photodynamic therapy in clinical human studies: The state of the art. Photodiagnosis and Photodynamic Therapy 2020;31:101828. https://doi.org/10.1016/j.pdpdt.2020.101828.
[17] Xiong Z-M, Mao X, Trappio M, Arya C, Kordi JE, Cao K. Ultraviolet radiation protection potentials of Methylene Blue for human skin and coral reef health. Scientific Reports 2021;11:10871. https://doi.org/10.1038/s41598-021-89970-2.
[18] Eickmann M, Gravemann U, Handke W, Tolksdorf F, Reichenberg S, Müller TH, Seltsam A. Inactivation of three emerging viruses – severe acute respiratory syndrome coronavirus, Crimean–Congo haemorrhagic fever virus and Nipah virus – in platelet concentrates by ultraviolet C light and in plasma by methylene blue plus visible light. Vox Sanguinis 2020;115(3):146-151. https://doi.org/10.1111/vox.12888