December 5, 2014

Jacob Schor ND, FABNO



A kind neighbor gave Rena and I a ride to Denver International Airport on Thanksgiving day, where the two of us boarded a flight to Chicago where after a short layover we boarded a second flight to Vienna and then again after another short spell, boarded a third flight to Tel Aviv.  This act of quickly crossing 9 time zones has given me good reason to ponder the phenomenon commonly referred to as ‘jet lag.’


Who was the first person was to suffer from jet lag? I expect the honor may be shared between Alcock and Brown who together made the first non-stop transatlantic flight on June 14-15, 1919, flying from Newfoundland to Ireland in less than 16 hours.


The actual term “jet lag” was first used in a Los Angeles Times article written by Horace Sutton published on February 13, 1966: "If you're going to be a member of the Jet Set and fly off to Katmandu for coffee with King Mahendra, you can count on contracting Jet Lag, a debility not unakin to a hangover. Jet Lag derives from the simple fact that jets travel so fast they leave your body rhythms behind." [1]


Commercial jet travel was just 14 years old when Sutton’s article was published.  The FAA was still pondering whether jet travels impacted circadian rhythms. The first PubMed indexed article on jet lag didn’t appear until 1967.  These early studies compared subjects traveling on intercontinental flights through multiple time zones, in multiple directions, east to west, west to east, north to south and so on.  While everyone felt tired, those traveling east to west experienced significant impairment in performance that didn’t occur on flights in other directions [2].   This finding is at odds with later studies that consistently find that eastbound flights are far worse than westbound flights. 


Jet lag is now a recognized sleep disorder with its own diagnostic code number (ICD-9-CM 327.35).  Crossing too many time zones too quickly for the circadian clock to adjust causes jet lag; a person’s circadian clock no longer matches local time. 


Normally circadian cycles are closely synchronized to the light dark daily cycle so that we are alert during the daytime and sleepy at night. When the internal hormonal signals don’t match the local day-night signals, we end up being awake and alert when we should be asleep.


The main symptoms of jet lag are nighttime insomnia and daytime sleepiness but symptoms can also include dysphoric mood, diminished physical performance, cognitive impairment, and gastrointestinal disturbances.  If that isn’t bad enough, other factors can sneak in that also result from traveling such as irregular sleep and meal times, dehydration, and so on that have nothing to do with crossing time zones, but still mess you up.  These later problems will adjust quickly with a few days rest but the circadian shifts can persist far longer.


looking north on the shore of the Dead Sea: 12-8-14


Incidence of jet-lag is unknown, but you have to figure that it impacts a high percentage of the 30 million plus jet travelers who leave the United States yearly for destinations that cross five or more time zones.


There are a couple of basic strategies that work to prevent jet lag, or at least that’s what one reads.  They include working to reset the circadian clock by both timing exposure to light and by taking supplemental melatonin and also by using drugs to counteract the symptoms both of night time insomnia and daytime sleepiness.


Core body temperature measurements are often used as the biomarker for checking circadian cycles.  Using these temperatures it was estimated that the circadian clock resets about 92 minutes later after one has flown westward but only 57 minutes earlier each day after an eastward flight [3].    Similar differences in time shifts have also been confirmed using melatonin levels as a biomarker for circadian timing [4]. 


Differences between flying eastward compared to westward show up in another way, the spike in salivary cortisol levels when awaking in the morning.  In a study of 764 men who crossed three time zones, flying east caused a steeper increase in morning cortisol levels on the first morning after arrival but then a lower peak level the next day. Flying westward resulted in lower waking cortisol levels the morning after arrival [5].


As the circadian clock seems to be set, or at least adjusted by light and dark exposures, it makes sense to try to reset the clock as much as possible as fast as one can. Exposing one’s self to light in the evening shifts the clock to a later time and exposure to light in the morning shifts the clock to an earlier time.  Though at some mysterious point during the night there is a crossover point when the evening response to light exposure, the phase delay, shifts to the morning response, phase advance.  If this sounds complicated to you, consider what it must feel like in my jet lagged brain.  Basically the best approach is to get outside and get as much bright sun exposure as possible and let that suprachiasmatic nucleus that controls circadian timing do the calculus on its own.  This works unless you have crossed eight or more time zones and then apparently the brain may confuse dawn with dusk and the current expert suggestion is to actually stay indoors after long eastward flights for a few hours after dawn and for a few hours before dusk after long westward flights [6].   So much for watching beautiful sunsets…..

Speaking of sunsets.... looking northeast toward Syria as the sunsets over the Golan


For short time zone hops one can of course simply try to stay on one’s own time schedule and ignore what’s happening in the new time zone.  In that case you should probably stay indoors and stay from those sunny cues that might reset your clocks.  It probably might help to try and shift your schedule a few hours even before your travel in the direction of your ‘new time zone’ using a combination of alarm clocks and bright lights to do so, but life typically gets hectic before big trips and some of us find that if anything we are shifting our sleep patterns in the opposite direction we might want to. As Robert Sack wrote about in the NEJM, “… this strategy requires considerable planning and discipline.” [7]


Melatonin supplementation is perhaps the best studied of therapeutic interventions for treating jet lag.  We consider this hormone as the ‘darkness signal’ as it has the opposite effect on circadian timing as exposure to light. When melatonin is taken in the evening it resets the body clock earlier and when taken in the morning it resets the clock later.  Melatonin also may help people fall and stay asleep.


Eight of ten clinical trials found that melatonin, taken close to the destination bedtime decreased jet lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than after 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. The benefit of using melatonin is likely to be greater the more time zones crossed, though it has less benefit for westward flights [8]. 


A series of systematic reviews on the use of melatonin for treating jet lag have been written by Andrew Herxheimer, the most recent published in April 2014 [9].  []


It’s interesting how little we actually know about jet lag considering how common an experience it is.  There are few if any similar experiences that human evolution may have prepared us for. 


There is a combination homeopathic remedy called “No Jet Lag” that is now quite popular to use when traveling.  It contains a curious combination of homeopathic remedies including Arnica montana, Bellis perennis, Chamomilla, Ipecacuanha and Lycopodium, all in 30C potencies.  While there may be a logic underlying the selection of these various homeopathic medicines, it has so far escaped me.    Nevertheless this hasn’t prevented me from using it and I kind of think it helps.


There are a number of websites that suggest four days of alternate day caloric restriction as useful for preventing jet lag [10]   Charles F. Ehret of Argonne's Division of Biological and Medical Research is given credit for this diet.  Ehret was involved in circadian cycle research in the 1970s and jet lag research into the 1990s.


According to Ehret, the traveler should start the diet four days prior to breakfast time at his destination. On day one the prospective traveler feasts, eating heavily with high protein breakfasts and lunches and then a high carbohydrate dinner.  Day two is ‘fasting day’ with only low caloric meals, salads, soups and juices.  Day three is again a ‘feast day’ and day four, the traveling day is a ‘fast day’.  I am not doing justice to how detailed this method is so if you are interested in trying this method, do read the detailed instructions online.

thinking about fasting... not an easy strategy to use while visiting family


An interesting article on self treating via acupuncture points:


The timing of when the mitochondria within individual cells are ready and eager to be active and ‘burn fuel’ is timed by circadian cycles in order to be in synch with mealtimes so perhaps Ehret’s diet makes sense as this regulation may go both ways; fasting may shift mitochondrial scheduling and in turn reset the circadian cycle, or at least reset the mitochondrial timing [11].   On the other hand it appears that the preprogrammed setting for mitochondria and appetite is to be hungriest in the evening [12].


Several interesting tidbits have been published during the past year.

A March 2014 paper using mice as test subjects suggests that exercise may be useful in restoring circadian patterns [13].    High fat diets alter the circadian cycle in mice [14].   A May 2014 paper reports that jet lag profoundly alters intestinal microbiota, again in mice [15].   This raises the question as to whether the Traveler’s Gastritis, typically blamed on intestinal infection from the destination’s water supply, may in fact be a symptom of jet lag, or a result of increased susceptibility due to biome disruption? 


Disruption of circadian cycles to mimic jet lag hastens development of type 2 diabetes in rats by hastening the destruction of beta-cells [16].    This too raises an interesting question; would we know it if jet lag was a contributing factor to the rise of diabetes in modern times?


Liver detoxification pathways are tightly regulated by circadian cycles and deeply disrupted by jet lag.  A drug easily tolerated at home may have a significantly stronger or weaker action on a person’s system when overlapped with jet lag [17].  Aside from knowing this potential problem there seems to be little information about what to do about this.


A fair bit of work has been done experimenting with ‘drugging’ people through jet lag, both drugging them to sleep and then to wake them up again.  As I’m not in a rush to try these methods for myself, nor advise them to patients, I am going to pretty much omit details about using sedatives or stimulants.


Well except for coffee.  I confess I’ve become quite enchanted with the instant Turkish style coffee that I find in our rooms.   Samuels, in his excellent summary of treating jet lag in athletic teams to maintain performance, suggests, “… the judicious use of napping and caffeine, both of which can synergistically improve the alertness of the athlete and reduce symptoms of fatigue.” I love it that he actually suggests a dose: “The strategic use of caffeine [eg, 50-mg to 200-mg pill or beverage (the average 5 oz cup of coffee contains 80 mg of caffeine; a 1 oz espresso contains 58 mg of caffeine.)]” [18].   The very thought of this strategy appears to have provoked an unrelenting desire in me to stop writing and start movement toward acquiring a dose of this herbal extraction least I again fall asleep on the keyboard.







2. Hauty GT. Individual differences in phase shifts of the human circadian system and performance deficit. Life Sci Space Res. 1967;5:135-47.


3. Aschoff J, Hoffmann K, Pohl H, Wever R. Re-entrainment of circadian rhythms after phase-shifts of the Zeitgeber. Chronobiologia. 1975 Jan-Mar;2(1):23-78.


4. Takahashi T, Sasaki M, Itoh H, Sano H, Yamadera W, Ozone M, Obuchi K, Nishimura H, Matsunaga N. Re-entrainment of circadian rhythm of plasma melatonin on an 8-h eastward flight. Psychiatry Clin Neurosci. 1999 Apr;53(2):257-60.


5. Doane LD1, Kremen WS, Eaves LJ, Eisen SA, Hauger R, Hellhammer D, Levine S, Lupien S, Lyons MJ, Mendoza S, Prom-Wormley E, Xian H, York TP, Franz CE, Jacobson KC. Associations between jet lag and cortisol diurnal rhythms after domestic travel.Health Psychol. 2010 Mar;29(2):117-23. doi: 10.1037/a0017865.

 Free PMC Article:


6. Eastman CI, Burgess HJ. How To Travel the World Without Jet lag. Sleep Med Clin. 2009 Jun 1;4(2):241-255.

Free PMC Article:


7. Sack RL. Clinical practice. Jet lag. N Engl J Med. 2010 Feb 4;362(5):440-7. doi: 10.1056/NEJMcp0909838. Review.


8. Waterhouse J. The prevention and treatment of jet lag?: It’s been ignored, but much can be done. BMJ?: British Medical Journal 2003;326(7384):296-297.


9.  Herxheimer A. Jet lag. Clin Evid (Online). 2014 Apr 29;2014. pii: 2303.




11. Peek CB, Affinati AH, Ramsey KM, Kuo HY, Yu W, Sena LA, Ilkayeva O, Marcheva B, Kobayashi Y, Omura C, Levine DC, Bacsik DJ, Gius D, Newgard CB, Goetzman E, Chandel NS, Denu JM, Mrksich M, Bass J. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science. 2013 Nov 1;342(6158):1243417. doi: 10.1126/science.1243417. Epub 2013 Sep 19.


12. Scheer FA, Morris CJ, Shea SA. The internal circadian clock increases hunger and appetite in the evening independent of food intake and other behaviors.

Obesity (Silver Spring). 2013 Mar;21(3):421-3. Free PMC Article:


13. Pendergast JS, Branecky KL, Huang R, Niswender KD, Yamazaki S. Wheel-running activity modulates circadian organization and the daily rhythm of eating behavior. Front Psychol. 2014 Mar 4;5:177. doi: 10.3389/fpsyg.2014.00177. eCollection 2014.


14. Kohsaka A, Laposky AD, Ramsey KM, Estrada C, Joshu C, Kobayashi Y, Turek FW, Bass J. High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab. 2007 Nov;6(5):414-21.


15. Voigt RM, Forsyth CB, Green SJ, Mutlu E, Engen P, Vitaterna MH, Turek FW, Keshavarzian A. Circadian disorganization alters intestinal microbiota. PLoS One. 2014 May 21;9(5):e97500. doi: 10.1371/journal.pone.0097500. eCollection 2014.

  Free PMC Article:


16. Gale JE1, Cox HI, Qian J, Block GD, Colwell CS, Matveyenko AV. Disruption of circadian rhythms accelerates development of diabetes through pancreatic beta-cell loss and dysfunction. J Biol Rhythms. 2011 Oct;26(5):423-33. doi: 10.1177/0748730411416341.

 Free PMC Article:


17. Zmrzljak UP, Rozman D. Circadian regulation of the hepatic endobiotic and xenobitoic detoxification pathways: the time matters. Chem Res Toxicol. 2012 Apr 16;25(4):811-24. doi: 10.1021/tx200538r. Epub 2012 Feb 24.


18. Samuels CH. Jet lag and travel fatigue: a comprehensive management plan for sport medicine physicians and high-performance support teams. Clin J Sport Med. 2012 May;22(3):268-73. doi: 10.1097/JSM.0b013e31824d2eeb.

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