How Jet Fumes And Hypoxia On Planes Affect The Body

Hypoxia (loss of oxygen) is a major stressor on the body.

On average, one can live ~21 days without food, ~2 days without water, but only a few minutes without oxygen. R

Most studies review long term exposure of hypoxia, but in this post we will discuss what happens to the body on a cellular level when exposed to hypoxia in the short term, such as flying or space travel (in a non-hormetic way). R. 

Almost two billion people use commercial aircrafts annually. R

When you go on a plane, you normally reach altitudes that cause hypobaric hypoxia (~2300m/8000ft). R

The higher you go into the atmosphere, air pressure (hypobaric) and oxygen (hypoxia) both become less available. R

This means there is less oxygen available to mitochondrial metabolism and less oxygen to saturate tissue, so the body must adapt to this stressor. R

This condition is called short-term hypobaric hypoxia (STHC) or intermittent hypobaric hypoxia (IHH) and as an adaptive response to keep to body in homeostasis, this creates proteopathy (misfolding of proteins). R R R

1. Starves Mitochondria

STHC causes mitochondria to produce more free radicals than it can quench. R

STHC limits the availability of oxygen for reduction to H2O2 at cytochrome oxidase. R

This leads to further production of ROS and RNOS. R

2. Reduces Cognitive Function And Brain Permeability

STHC may reduce cognitive function. R

STHC causes cognitive impairment (affecting memory function specifically) causing hippocampus mitochondrial and synaptic lesions. R

As seen in astronauts, STHC may induce with swelling of the optic disc due to disruption the blood-brain barrier (BBB) and result in cerebral edema. R

STHC in the brain and vascular system decreases expression of the gene Apo-E. R

This reduction in Apo-E makes it harder to protect against glutamate-induced cell death.R

Apo-E also has many effects such as antioxidant, anti-platelet aggregation, anti-proliferative effects, and immunomodulation properties. R R R R

3. Induces Headaches

Changes in cabin pressure during take-off and landing can cause airplane headache (AH). R R R

AH has been commonly associated with anxiety. R

CGRP and VIP levels may be decreased during AH (needs further research). R

4. Impairs Liver Function

STHC may induce insulin resistance as it reduces retinol binding protein (RBP4) which down-regulates GLUT4 (insulin-dependent factor that moves glucose into fat/muscle). R

This also releases more retinol (in free form) into the extracellular space of the cell (10x more than normal). R

In animal models, STHC has shown to increase gluconeogenesis in the liver. R

5. Increases Coagulation

STHC increases the risk of thrombosis. R R

This increases the risk of developing stroke, chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSAS). R R R

Flying (STHC) triggers systemic inflammation and platelet activation,  which leads to coagulation induction and degranulation of platelets. R 

Also, STHC reduces Apo-M (protects LDL from oxidative stress) and Apo-H (prevent activation of the intrinsic blood coagulation). R R

It may also make sickle cell disease worse as it causes sickling of blood cells. R

STHC increases hypoxia-inducible factor-1 and -2 (HIF1a and HIF2a) and causes iron dysregulation in the blood. R

6. Reduces Lung Function

Higher altitudes alter pulmonary function and may make respiratory conditions worse (such as COPD, asthma, pneumothorax, bronchogenic cysts, restrictive pulmonary diseases, cystic fibrosis and pulmonary hypertension). R

As an adaptive response in STHC, ApoA-I gene expression increases. R

ApoA-I protects arteries in the lungs, maintains airway function, and helps prevent inflammation and collagen deposition in the lung. R

7. Worsens Wound Healing

STHC reduces fetuin. R

Fetuin plays as an anti-inflammatory mediator that is critical to regulating the innate immune response following tissue injury. R

8. Damages Vision

STHC may cause optic neuropathy (OD). R

For example, in a case study, a 12 hour flight caused a patient to develop OD in the right eye. R

STHC may also induce myopia. R

For example, in another case study, a patient developed myopia in his right eye after a plane landing. R

9. Worsens Exercise Performance

Exposure to moderate altitude accelerates destruction of muscle tissue. R

It also increases the ability for muscles to become fatigued (as STHC accelerates the transition from the slow-to-fast-twitch fiber type and decreases mitochondrial function/aerobic metabolism in muscles). R

Training in hypoxia, Intermittent induced cyclic hypoxia (IICH), has been studied recently in athletes. R

IICH can stimulate erythropoietin and red blood cell production and increase ventilation. R

IICH may also increase arterial blood pressure through activation of the reninangiotensin system in healthy subjects. R

It also enhances sympathetic and blood pressure responses to acute hypoxia and hypercapnia. R

However, exercise with oxygen therapy (EWOT) + IICH does show some benefits (see separate post). R R

10. Decreases Immune Function 

Reactivation of latent herpes viruses often occurs during short-duration flights. R

STHC suppresses the immune system - T cell function is impaired during hypoxic stress and promotes the accumulation of extracellular adenosine as a result of enhanced purine nucleotide degradation from adenosine tri- and diphosphate (ATP, ADP). R 

11. Worsens Inflammatory Bowel Disease 

Flying can cause Inflammatory Bowel Disease (IBD) flares. R

Crohn's Disease (CD) and Ulcerative Colitis (UC) patients have shown to have elevated levels of HIF-1α and HIF-2α. R R

12. Impairs Sleep And Jet-Lag Recovery

Flying with STHC may reduce the ability to sleep and make jet-lag symptoms worse. R

13. Alters Water Intake

STHC reduces water intake. R

Jet Fumes, Cabin Air, And Aerotoxic Syndrome

Most human and animal studies show the effects of jet fumes to be pretty benign, but are not completely harmless. R

They have been linked to aerotoxic syndrome (ill-health effects caused by breathing contaminated/toxic airliner cabin air). R

Exposure to jet fumes in the respiratory system have shown to cause the production of phlegm, cough, and asthma. R

Studies have also shown that neurotoxins found in cabin air jet fumes have been linked cognitive impairment and loss in brain white matter. R R R

Also, long-term studies of US flight attendants show a possible link to:

• Breast cancer - circadian disruption disrupts melatonin production and may worsen EMF radiation R

• Neurodegeration - suggesting that flight attendants may have an increased risk of Amyotrophic lateral sclerosis (ALS) R

These fumes may get in via engine bleed, which is called a fume event - if an engine bearing seal fails and begins to leak, depending on the location of the seal, some amount of engine oil may be released into the compressed air stream. R

Jet fuel (such JP-8) and jet oil are commonly linked to aerotoxic syndrome and many chemicals from them can be inhaled including: R R R

• Benzene R

• Dioxins R

• Furans R

• PAHs R

• Organophosphates R

• Ozone R R

• VOCs R

Exposure to these chemicals may increase risk for developing cancer or other pathologies in humans who are occupationally exposed (such as air force, airport/airplane workers, and firefighters). R R R

Exposed flight-crew members have reported symptoms, including dizziness, nausea, disorientation, blurred vision, and tingling in the legs and arms. R

Cabin air also has flame retardants circulating from plane materials, which are known carcinogens. R

Carbon Dioxide

Recirculated air increases the amount of carbon dioxide (CO2). R

CO2 may: R

• Alter behavioral health and performance - irritable, lethargic, visuomotor impairment, nausea, dizziness, derealization, fear of losing control, and paresthesia

• Alter bone homeostasis - results in acidosis and the release of calcium carbonate and bone breakdown, so may cause kidney stones

• Alter the binding of oxygen in blood - less O2 is bound to hemoglobin

• Stimulate hyperventilation - has shown to cerebral blood flow (CBF) by up to 35%, without returning to baseline post-exposure

• Vasodilate the brain

Check oxygen levels with a SpO2 meter (only represents blood oxygen, not cellular).

Lifestyle:

• Drink Water

• Hyperbaric Oxygen Therapy (possibly)

• Wear Elastic Stockings / Compression Socks - May help prevent thrombosis during long flights R

Supplements:

• Ginkgo Biloba -helps with HH adaptation R

• Glutamine - protects from intestinal injury and regulates the gut flora imbalance in hypoxia environment R

• Nitrates (or Neo40)- improves blood flow and is paramount if training (exercising) in hypoxia R R

• Quercetin - helps improve brain/mitochondrial function via Sirt1/PGC-1α/FNDC5/BNDF R

• Rhodiola -improves HH R

• Vitamin E - improves intestinal barrier function R

Drugs:

• Antihistamines - may help with airplane headaches (decreases sinus mucous) R

• NSAIDS - may help with airplane headaches via PGE2 R

Pathways:

• Increase GPX R

• Increase NRF2 - helps with acute mountain sickness R

• Increase SOD1 R

• Increase SOD2 R

Hypoxia Tolerance

In humans, hypoxia tolerance improves with increased nitric oxide availability, so consuming greens or supplementing with nitrates may help improve tolerance. R

Another reason for eating greens (or meats) is to increase iron levels, which help with STHC adaptation. R

Also, hypoxia tolerant animal models shower higher levels of the following proteins, so upregulating their expression may be beneficial: R

• Increase CRP

• Increase CLC11

• Increase GPx-3

• Increase Hp

• Increase PON1

• Increase Rab-3D

• Increase TTR

• Reduce C3

• Reduce C4

Hypobaric Hypoxia:

• Increases AAT R

• Increases Aldosterone R

• Increases APOA1 R R

• Increases CLU R

• Increases CRP R

• Increases C1QA R

• Increases C1QB R

• Increases Enoyl CoA hydratase R

• Increases F2 R

• Increases GAPDH R

• Increases GST-P1-1 R

• Increases HBA R

• Increases Hemopexin R

• Increases HP R

• Increases IL-6 R

• Increases Myoglobin R

• Increases NMDA R

• Increases PAI1 R

• Increases Prothrombin R

• Increases Renin R

• Increases sP-selectin R

• Increases TAT R

• Increases TTR R

• Increases VDBP R

• Reduces ALB R

• Reduces Amyloid (serum) R

• Reduces APOE R R

• Reduces Apo-H R

• Reduces CAT R

• Reduces CA1 R

• Reduces Cortisol R

• Reduces C3 R

• Reduces C4a R

• Reduces Fetuin R

• Reduces PGK1 R

• Reduces RBP (plasma) R

• Reduces Transferrin R

Jet Fumes

• Increases LDH R

FAM213A

rs77999529

• Exhibits a low minor allele frequency in various human populations  (may be beneficial for high-altitude adaptation studies have shown accelerated growth in lung volume and chest dimensions in highlanders vs. lowlanders, which might be a developmental compensatory response to high-altitude hypoxia) R

rs150230265

• Exhibits significant allele frequency differences between highlanders vs lowlanders (may be beneficial for high-altitude adaptation studies have shown accelerated growth in lung volume and chest dimensions in highlanders vs. lowlanders, which might be a developmental compensatory response to high-altitude hypoxia) R

SFTPD

rs3923564

• G allele - risk allele for chronic obstructive pulmonary disease R

rs7078012

• T allele - risk allele for chronic obstructive pulmonary disease R

rs3088308

• serine to threonine subsitution - damaging and exhibits significant differentiation between HL and LL R

rs721917

• Thr/Thr genotype - had significantly lower SP-D serum levels, and is associated with increased disease-susceptibility R

• Met allele - associated with defense to respiratory syncytial virus R

rs2243639

• Thr/Ala - more common in highlanders vs. lowlanders (may be beneficial for high-altitude adaptation studies have shown accelerated growth in lung volume and chest dimensions in highlanders vs. lowlanders, which might be a developmental compensatory response to high-altitude hypoxia) R R R

• Reduces SpO2 levels may correlate with flight phobia (not well researched). R