shifted rapidly—but not entirely—during night-
time work. The excretory maximum occurred
when the physical and mental demands of the
night shift were greatest?®.

Another way of studying the effects of chang-
ing light-dark ratios is to observe men living
(temporarily or permanently) at high latitudes.
Natives of the arctic region, where the normal
stimuli of sunrise and sunset are absent for a
considerable portion of the year, showed a cer-
tain decrease in the amplitude of all components
of the 24-hour urinary excretion cycle; during
the extremes of the season these rhythms some-
tinues even disappeared completely". These fluc-
tuations seem to indicate, not an entrainment of
the rhythms by the changing light-dark ratio,
but rather a damping effect on the naturally oc-
curring cycle.

The effects of long periods of abnormal work
and abnormal time routines on physiological fune-
tions in man were studied in a series of experi-
ments conducted in Troms (Norway) and Spitz-
bergen. Groups of subjects lived and worked on
21-hour, 24-hour, and 27-hour schedules”. The
body temperature cycle of these men adapted al-

“most immediately to the abnormal routines**.
The urinary excretion cycle was disturbed only
in the early daylight period and was reestablished
after about 2 weeks. In contrast, the potassium
excretion cycle adhered more closely to its nor-
mal 24-hour pattern throughout the entire pe-
riod‘. The excretion cycles of the 17-hydrox-
ycorticosteroids and electrolytes adjusted to the
changed routines within 5 weeks or more. The
adaptation was delayed when the experimental
“days” fell within periods which corresponded
to deep sleep periods at home”.

Several laboratory studies have been made by
various investigations under controlled condi-
tions in order to determine the effects of changes
of the light-dark ratio on the body’s circadian
rhythms and, as a corollary, to ascertain the
effect of desynchronization on human perform-
ance’, The test subjects in these studies were
isolated singly or in groups for various periods.
In one study at Baylor University, Houston,
Texas, the subjects lived for 1 week on a schedule
of light and darkness comparable to that of a
normal day. During the next 6 days, the “sun-
rise” was advanced 30 minutes each day, so that
by the 6th day it was at 3 a.m. and “sunset” was
at 7:00 pam. This schedule was continued for

3 days. Then, beginning on the 17th day, the
light was kept on for the rest of the 30-day test
period. In this study the following physiological.
measurements were taken: body temperature,
blood pressure, pulse rate, volume and osmolarity
of urine, and urinary content of epinephrine,
norepinephrine, corticosteroids, creatinine, so-
dium, potassium, and chloride. Psychological
and perceptual tests were also administered, and
electroencephalograms were taken at certain in-
tervals.

The most significant finding of the Baylor ex-
periment was the discovery that, while the circa-
dian periodicity shifted gradually with a gradual
shift of the light-dark ratio, an abrupt change
to constant illumination resulted in a severe dis-
ruption in the biological rhythm pattern, which
became grossly distorted. The performance of

“ discrete and sensitive motor and sensory. tasks

was impaired as a result of this disruption, but
gross motor functions were unaffected. The af-
fected functions were reentrained after about 3
days of constant light, but the cycle was slightly
longer than 24 hours. Extremely long periods
of isolation (6 monthes and longer) resulted in
a relatively stable body temperature and sleep-
wake rhythm but in a desynchronization of the
activity cycle. The subjective concept of time
became distorted ; specifically, subjective estimates
of time increased considerably in the course of
these experiments. The dissociation of certain
functions and the effect of the shifts of the light-
dark ratio on psychophysiological processes in-
dicate that the light-dark ratio and the individ-
ual’s work schedule, degree and kind of activity,
social habits, and sleep pattern interact in ways
yet to be clarified.

The Air Traveler and Circadian-Rhythm

/Desynchronization

Circadian rhythms became a matter of im-
portance to travelers with the evolution of the
airplane and the feasibility of long-distance
flights. Wiley Post, the record-setting global
flier of the 1930’s, was the first to recognize the
adverse effects of time-zone displacement on the
sleeping and eating cycles of air travelers‘.
Prior to his 8-day global flight of 1931 and his
7-day'solo global flight of 1933, Post determined
the effects of altered sleep-wake cycles on his
flying proficiency. He also experimented with



Applications of Data on Circadian Rhythm

The International Civil Aviation Organization
(ICAO) has its headquarters in Montreal and
has a membership of 116 countries. Because its
staff members travel frequently from country to

-/country, ICAO has evolved a travel-time formula
to help insure that disturbance in circadian
rhythm neither works a hardship nor impairs
cerebral function on trips to distant places. En-
lightened policies of this type are being adopted
by the management of other progressive organiza-
tions and corporations, insuring optimum effi-
ciency on the part of their traveling representa-
tives. The immediate and long-range benefits to
the parent organization may not be apparent at
first, but they have a sound biological basis. The
benefit to the traveler—in terms of lessening of
fatigue—of the use of formulas such as that used
by ICAO is obvious.

i“ The ICAO formula is as follows:

Rest period (in
tenths of days) = ‘

Travel time
(in hours) Time zones in
2 excess of 4 +
Departure time Arrival time
coefficient + coefficient
(local time) (local time)

The departure and arrival time coefficients are
given in Table 1.

Lloyd Buley, chief of ICAO’s Medical Section,
states that, in general, adherence to the ICAO
formula has had the desired results. The in-
creased weighting given the later hours for de-
partures helps compensate for the effects of loss
of sleep. Also, the high arrival-time coefficient
for the period 0800 to 1159 hours (Table 1) helps
compensate for the disruptions experienced dur-
ing early morning flights plus the effect of ar-
riving at the beginning of a workday without
sufficient rephasing of the circadian rhythms.
The amount of phase difference is accounted for
in the formula by the term “time zones in excess
of 4.”

In applying the formula, the following rules
are observed by ICAO.

y (1.) The value obtained for rest period, in
tenths of days, is to be rounded to the nearest
higher half day. However, rest stops that add up
to less than a day before rounding will not be

scheduled unless the journey involves an over-
night flight on mission travel.

v(2.) “Travel time, in hours” means the num-
ber of hours of elapsed time required for the
journey, in accordance with the published sched-
ules of the airline, rounded off to the nearest hour.

(3.) “Time zones” are computed in increments
of 15 degrees of longitude from Greenwich.

(4.) “Departure time” and “arrival time” are
local times.

The computation (according to the formula)

for determining the rest periods for flights from

Montreal to London and back could be as follows.
For the west-to-east flight, (6/2)+1+3+3=
10/10 day, or 1 day; thus 1 day of rest would be
allowed in London. For the return trip, the fig-
ures might be (7/2) +1+1+2=7.5/10; no extra
day of rest would be given in Montreal since over-
night flight was not involved (see rule 1).

The computation for flights from Montreal to
Karachi and back could be as follows. For the
west-to-east flight, (26/2) +5+4+3=25/10; thus,
21% days of rest would be allowed in Karachi.
For the return trip, the figures might be (26/2)-
+5+4+2=24/10; thus 214 days of rest would
be allowed in Montreal.

For the north-to-south flight from Montreal to
Mexico, the computation could be as follows:
(7/2) +0+1+0=4.5/10; thus, no day of rest
would be given. However, the computation for
a flight from Montreal to Lima might be (15/2)-
+0+1+4=12.5/10, and 1% days of rest would”
be given. Some flights might involve north-
south travel across several time zones. The com-
putation for a flight from Montreal to Sydney
might be (31/2) +5+0+3=93.5/10; thus 214
days of rest. would be given in Sydney. The In-
ternational Radiation Commission, with head-
quarters in Vienna, utilizes the ICAO formula in
planning long trips for its staff.

There is another possibility: Can the critical
circadian rhythms be readjusted prior to de-
parture to be in phase with the time of the city
of destination? The sleep cycle—the most ob-
vious, and posibly the most critical, of the
rhythms—can be modified within limits. The
Deparment of Psychiatry and the Brain Research
Institute at the University of California, Los
Angeles, held a symposium in May 1968, entitled
“Physiology and Pathology of Sleep,” at which
various reports of successful alterations of sleep


fatigue than older pilots, and that pilots should
receive more flight credit for hours of flight
from east to west or from west to east than for
the same number of hours on a north-south route.
When the trips were extended to Anchorage,
Alaska, the analysis of some hormonal reactions
yieled evidence of pronounced and stable circadian
variations in excretion of the 17-OH corticoste-
roids; the other functions studied were not ap-
preciably modified during a stopover in Anchor-
age. However, after 5 days the pilot’s renal and
plasma hormonal cycles were fully adapted to
local time, and different from the cycles observed
before the departure from Paris.

Table 1. Departure and arrival time coeffcients used-

in the ICAO formula (see text).

Departure Arrival
Period time time

coefficient coefficient
0800-1159 hours 0 4
1200-1759 hours 1 2
1800-2159 hours 3 0
2200-0059 hours 4 1
0100-0759 hours 3 3

French aeromedical specialists responsible for
an operational area which extends through the in-
ternational dateline and some distance north and
south of the equator, studied groups of subjects in
a first attempt to develop a geographical map of
circadian functions in relation to local time*.
They found a 4~hour shift in the rhythm of sev-
eral basic biological functions after a 5~hour
change in time, but no dissociation of normally
associated functions. The functions appeared to
drift from the base rhythm after a 10-hour shift
from local time; this shift, reportedly, was
physiologically more disconcerting than two
5-hour shifts.

Dutch scientists recorded the diurnal rhythm
in‘the excretion of water, chloride, sodium, and
potassium for subjects during flights from Am-
sterdam to New York and back. The experiment
lasted 5 days, with a stay of 4 days in New York
and return flight on the 5th day. In a second
experiment, the subjects were returned to Am-
sterdam after a stay of only 214 hours in New
York**. When the subjects arrived in New York
the maxima of their excretion cycles were un-
changed. Those who stayed in New York did not

adapt to the New York time cycle, and the am-
plitude of the rhythms for excretion of water
and electrolytes decreased. In subjects who had
flown from Amsterdam to Anchorage”, the max-
ima of the excretion cycles shifted by the 6th
day after arrival. However, the amplitudes of
the rhythms were depressed, and in subjects who
flew on to Tokyo, the rhythm disappeared com-
pletely. In addition to some desynchronization
in rhythm pattern, the amounts of water and
electrolytes excreted deviated temporarily from
normal values. These deviations, which were
thought to be caused by the stresses involved in
air travel, seemed not to affect the process of
adaptation, however.

Only recently have Japanese scientists studied
physiological responses to the time shifts asso-
ciated with long-distance flights’. They recorded
the diurnal pattern of body temperature of trav-
elers after an eastbound flight that involved a
time shift of 10 hours. This time shift disrupted
the normal temperature cycles; these were grad-
ually reestablished after approximately 13 days
(during this time the maximum of the cycle
shifted by 40 to 50 minutes per day).

/Russian scientists have studied the effects of
rapid time-zone changes on their pilots flying
through 11 time zones on routes within the
U.S.S.R. These studies are, of course, conducted
without the need for passports and all the other
complications of international travel which are
encountered by scientists of other countries mak-
ing similar studies. In preparation for the di-
rect New York-Moscow air link, there was an
exchange of information between U.S. and Soviet
aviation personnel, which included familiariza-
tion with the flight equipment, operational pro-
cedures, and regulations of the other country.
The Soviet Ministry of Civil Aviation revealed
in 1967 that studies of responses to time-zone
shifts have been made along the Moscow-Khab-
arovsk-Moscow route’. Flights over this route
require 8 to 9 hours of flying time. The Russians
observed changes in certain physiologic variables,
in visual factors, in electroencephalograph and
electrocardiograph recordings, and in blood pres-
sures. They also reported subjective symptoms
of fatigue in individual pilots, which they at-
tributed to “the difference in astronomic time be-
tween the geographical points.” Also, disturb-
ances were found in the relaxation, sleep, and
feeding schedules of the crew members, which



an irregular schedule of meals and worked out
a conditioning program designed to break his
habitual sleeping and eating patterns. As indi-
cated in his book", Post felt that the time-zone
effects were significant and that the steps he took
to adjust to them were beneficial.

The next published discussion of time-zone ef-
fects in global flying is a 1952 report by Strug-
hold**. Since then, and especially since jet-
powered air transports were introduced in the
late 1950’s, the literature on aerospace medicine
has contained many papers on “jet age” time-zone
effects. Crew members and passengers have re-
peatedly reported adverse physiological and psy-
chological consequences of rapid long-distance
flights—of east-to-west or west-to-east flights in
particular.

In recent years, several studies have been made
of passengers and crew members under real flight
conditions and of volunteer subjects under stimu-
lated flight conditions, in an attempt to assess
the immediate and delayed effects of diurnal
rhythm desynchronization. Several of these
studies are reviewed here. Almost all countries
that have aircraft making long transcontinental
and intercontinental flights are investigating
time-zone effects. Although the “ultimate”

Jstudy has not yet been made, several investiga-
tions have provided enough data to make pos-
sible certain travel-policy decisions.

V British scientists at the Royal Aircraft Estab-

lishment in Farnborough, England, made bio-
medical studies on pilots of planes making inter-
continental flights; these studies encompassed the
flight phase and periods immediately preceding
and following the flights*°. They showed that
the pilot’s heart rate varied directly with (1)
the flight workload; (2) the type of airplane (the
rate for a pilot landing the Boeing 707 was 128
beats per minute; that for one landing the VC-10,
100 beats per minute); (3) the nature of the
approach aids and airports (when aids were
limited and the airport poor, the heart rate was
higher) ; and (4) the weather.

r These physiologic responses are super-imposed
upon the circadian rhythms and upon the time-
zone desynchronization. An algebraic summa-
tion, for a particular flight, of (1) workload
stresses, (2) circadian rhythm nadir, and (3)
time-zone desynchronization may, for a partic-
ular crew member, lead to a potentially dangerous

impairment in performance. Recognizing this,
v the United Kingdom issued new guidance in-

formation on flight-time limitations. This
reads in part as follows:
Article 47 of the Air Navigation Order... is de-

signed to ensure that no crew member of a British-
registered aircraft which is either engaged on a
flight for the purpose of public transport or is being
operated by an air transport undertaking is sub-
jected to excessive fatigue. It requires the aircraft
operator, after taking into account the particular
circumstances of his operations, to include in his
operations manuals or comparable documents de-
tails of his limitation on flight times and flight
duty periods, and of the minimum rest periods he
has established.

The guidance information then recommends
J/that “long-haul operators should ensure that
their crews are properly briefed on the phy-
siological effects of time zone changes so that
they can adjust their sleeping pattersn accord-
ingly, and should bear this factor in mind when
scheduling rest periods between flights.” The
recommendation is made that “in the event of
Ahere being a time zone change of four or more
hours between the place of departure and the
place where the duty ends, the subsequent rest
period should not be less than twelve hours.”

Vv Aeromedical specialists at the Institut fur
Flugmedizin in Bad Godesberg, Germany, used a
battery of nine psychophysiological tests and a
questionnaire to determine the stress of flight
and of time-zone changes on Lufthansa pilots on
the North Atlantic route**. After having estab-
lished the rhythmicity of the psychological and
physiological functions in base-line studies, they
determined the shifts in peak that occurred during
actual flights. The investigators found the fol-
lowing relationship: the greater the interval be-
tween the time of departure and the time of
maximum activity or efficiency of the pilot, the
greater the stress experienced by the crew. They
also concluded that performance failures (and
probably accidents) are more likely to occur
during the hours of lowered resistance to stress.

v As a result of these studies it was recommended
that intercontinental flight crews be rescheduled,
consideration being given to departure time, flight
duration, and multiple landings.

French scientists studied the responses of Air
France pilots on flights extending through five
time zones on the Paris-New York route. They
reported that younger pilots suffered less from


observed for several physiological parameters dur-
ing flights from the United States to Japan.
These findings are supported by results of animal
experiments, which also indicate that it is much
easier to delay the circadian rhythm than to
advance it**, The physiological “advance-delay”
phase differences in these cases apparently over-
ride any psychological effect of displacement as
opposed to the return home.

In contrast, the results obtained by Aschoff and
Wever in Germany point in the opposite direc-
tion**, After experiments with birds had showed
that reentrainment occurs more quickly after a
single shortening of the Zeitgeber period than
after a lengthening of that period, an experiment
with a human subject was conducted in an air-
raid shelter in Munich. On the 6th day of isola-
tion the artificial night was shortened by 6 hours,
in simulation of a west-to-east flight; on the 13th
day the night was lengthened by 6 hours, in sim-
ulation of the return flight. After the “eastward
flight” the subject’s body temperature was im-
mediately in phase with the periods of light and
darkness, but after the “westward flight” it took
about 3 days for the activity cycle, and 5 days
for the body-temperature cycle, to shift back to
normal, These data are in line with Wever’s
mathematical model, which predicts that reen-
trainment should be accomplished in a shorter
time after west-to-east than after east-to-west
flight.

The findings by some investigators that flights
from a given location to a point farther west are
more disruptive of diurnal rhythms than the op-
posite case are in contrast to conclusions drawn
by other investigators. The resolution of these
differences is of scientific interest and also has
practical implications. The following questions
arise: (1) Can the effects of time-zone shifts be
realistically simulated in laboratory experiments?
(2) Is the entrainment model truly applicable to
the conditions that exist in geographic disloca-
tions? (3) Do bidirectional or even tridirectional
differences truly exist? (4) How serious are the
physiological and psychological effects of time-
zone shifts on airplane crew members and pas-
sengers? (5) Does circadian desynchronization
impose such stress on the human organism as to
significantly impair efficiency? (6) What meas-
ures can be taken to attenuate or compensate for
the deleterious effects of time-zone shifts if they
degrade performance?

Time-Zone Nomograph

Figure 1 shows a representative diurnal curve
(such as might be recorded for body temperature,
heart rate, performance, or other cycles). Above
the curve is a time scale for a time zone to which
an individual is adapted. Below the curve are
times scales for zones 7 hours to the east and 7
hours to the west.

If a traveler leaves on a nonstop flight from
New York to Rome (a 7-hour flight, crossing
seven time zones) at 1830 hours, he will arrive at
0830 hours local time, which is 0180 hours New
York time. He is thus biologically ready to sleep,
and not hungry. However, with sufficient con-
scious effort, he can immediately engage in busi-
ness meetings, tours, meals, and social functions,
but probably at less than peak efficiency for the
first 24 hours.

The return flight, after the traveler has be-
come fully adapted to the local time, leaves Rome
at 1100 hours and arrives in New York at 1415
hours, after a 10-hour flight. Sleep, which is
“due” in 2 or 3 hours, may be delayed for a while,
but the “biologic clock” starts its awakening
process by late evening, and sound sleep, once at-
tained, is hard to maintain. The traveler cannot
achieve sleep by the conscious effort which per-
mitted him to perform acceptably after his ar-
rival in Rome. Moreover, the stomach is very
time-conscious, and hunger for breakfast, which
is “due” at 0100 hours, may further add to his
discomfort. Adaptation after westward flights
can thus be expected to take longer than adapta-
tion after eastward flights of the same length.

These are but two examples, given in general
terms. There are obviously many variables which
govern the symptoms an individual experiences.
These include times of departure and arrival,
length of flight, direction of flight, layovers,
travel experience, stress, age, physical condition,
food and liquor consumed during flight, sleep
during flight, climatic changes, and the new social
environment. The normal diurnal curves for tem-
perature and heart rate can be affected by the
social environment. With the supersonic trans-
port it might be possible to arrange for crews
to make a round trip in one day, thus keeping
them adapted to one time zone. Except in the
case of longer trips with fewer layovers, the
effects of supersonic travel on passengers should
not be significantly more (or less) disrupting than
present jet travel.



AM 69-17

TIME-ZONE EFFECTS ON THE LONG DISTANCE AIR
TRAVELER

P. V. Siegel, M.D.
Siegfried J. Gerathewohl, Ph.D.
Stanley R. Mohler, M.D.

Approved by Released by
Z mo
Stamey & “neh
Srantey R. Mouter, M.D. P. VY. Sreezt, M.D.
Cuter, ArromepicaL APPLICATONS Feperat Ai Surcron
Drviston

September 1969

Department of Transportation

FEDERAL AVIATION ADMINISTRATION
Office of Aviation Medicine



L

10.
11.
12.

13.
14.

16.

REFERENCES AND NOTES

For summaries of the literature on circadian
rhythms and for reports on contemporary studies,
see F. A. Brown, J, Science 130, 1535 (1959); J.
AscHOFr, Symp. Quant. Biol 25, 11 (1960) ; F. Har
nee, ibid., p. 289; C. 8. Prrrenperax, ibid., p. 159;
J. BE. Harker, The Physiology of Diurnal Rhythms
(Cambridge Univ. Press, Cambridge, England, 1964) ;
E. Bunnine, The Physiological Clock (Springer,
Berlin, 1964) ; A. Sortpercer, Biological Rhythm Re-
search (Blsevier, Amsterdam, 1965) ; “Federal Avia-
tion Administration, Circadian Rhythms (Selected
References).” Bibliographic List No. 15 Washington,
D.C. (1968).

B. FRANKLIN, quoted in A Treasury of Science, H.
Saptey, S. Raprorr, H. Waren, Eds. (Harper, New
York, 1943), p. 186.

. C. J. Cortiss, The Day of the Two Noons (Associa-

tion of American Railroads, Washington, D.C. 1949).
CG. S. Prrrenprian, Symp. Quant. Biol. 25, 277 (1960).

. . AscHorr, in Man’s Dependence on the Earthly

Atmosphere, K, B, Scranrer, Bd. (Macmillan, New
York, 1962).

BE, A, AtLuist and W. D. Cuites, Acta Psychol. 27,
436 (1967).

K. HorrMan, in Circadian Clocks, J. Ascuorr, Ed.
(North-Holland, Amsterdam, 1965); E. Bunwine,
Ann. N.Y, Acad. Sei. 138, 515 (1967).

. J. H. van Loon, Acta Physiol. Pharmacol. Neerl. 8,

302 (1959).

Hun Kr Mr, J. E. Jones, E. B, Frick, Fed Proc.
25, 917 (1966).

A. Kosma and Y. Nryama, Ind. Health 8, 9 (1965).
M. ©. Lossan, Symp. Quant. Biol. 25, 325 (1960).
P. R. Lewis and M. C. Loppan, Quart. J. Exp.
Physiol. 42, 356 (1957).

—, ibid., p. 871.

M. C. Loppan and H. W. Simpson, J. Physiol. Lon-
don 155, 64P (1961).

. M. C. Lopsan, in Circadian Clocks, J. AscHorr, Ed.

(North-Holland, Amsterdam, 1965), pp. 219-22’
H. W. Surpson and M. C. Lossan, Aerospace Med.
38, 1205 (1967).

F. Gurrrrzen, Aerospace Med. 37, 66 (1966); T. W.
Frazier and J. A. RuMMEL, ibid. 39, 383 (1698); J.
Amer. Med. Ass. 199, No. 5 (1967); F. Gerrrrzen, T.
Srreneurs, 8. Esser, Acrospace Med. 40, 264 (1969) ;
J.D. Finpey, B. H. Mrerer, J, V. Brapy. “A long-
term study of human performance in a continuously
programmed experimental environment,” Space Res.
Lab. Tech. Rep. Ser. College Park, Md. (1963); J.

10

17.

18.
19.

20.

21.

ie
Ss

23.

24,

27.

28.

Ascuorr, inJan’s Dependence on the Earthly Atmo-
sphere, K. E. Scuaerer, Ed. (Macmillan, New York,
1962); ——, Science 148, 1427 (1965); K. E.
Scwaerer, B. R. Curae, C. R. Carry, J. H. DoucHerry,
B. B. Weyprew, Aerospace Med. 38, 1002 (1967);
J. Coun, Y. Noupas, C. Bourenter, J. Trmpar, M.
Strrre, “Etude du rythme circadien de la temperature
centrale d’un au cours q'isolement souterrain de 6
mois,” paper presented at the 16th International Con-
gress of Aviation and Space Medicine, Lisbon, 1967.
W. Posr and H. Garry, Around the World in Hight
Days (Hamilton, London, 1931).

H. Srevanonp, J. Aviation Med. 23, 464 (1952).

S. R. Mouter, J. R. Ditte, H. L. Grssons, Amer. J.
Public Health 58, 1404 (1968).

J. S. Howrrr, J. 8S. Barxwitt, T. C. D. WHITESIDE,
P. D. GV. Warrrincuam, Flight Personnel Research
Committee Rep No. 1240 (Ministry of Defense, Great
Britain, 1965) ; Flight Personnel Research Committee
Rep. No. 1264 (Ministry of Defense, Great Britain,
1966).

“Board of Trade Guidance Publication: Flight Time
Limitations—The Avoidance of Excessive Fatigue in
Aircrews” (Her Majesty's Stationery Office, London,
1967).

. K. E, Keer, H. Bruner, 8. Rurr, Z. Flugwiss. 14,

109 (1966) ; H. M. Weemann and H. Bruner, Aero-
space Med. 39, 512 (1968).

L.Lavernue, E. Larowrare, R. Larranr, Rev. Med.
Aeronaut. 4, 30 1965) ; “Les rhythmes cireadiens des
activities cortico-surrenale et medullo-surrenale in-
fluence des decalages horaires,” paper presented at
the 16th International Congress of Aviation and
Space Medicine, Libson, 1967.

J. Gwata, P. Fours, F. Borrey, “Application de
Petude des variations circadiennes a Vanalyse des
vols comportant Je passage de fuseaux horaires,”
paper presented at the 16th International Congress
of Aviation and Space Medicine, Lisbon, 1967.

). F. GeRRiTzen, Aerospace Med. 38, 697 (1962).
26.

—, T. Srrencers, S. Esser, “The behavior of the
circadian rhythm in water and electrolyte excretion
before, during and after a flight from Amsterdam to
Anchorage and Tokyo,” paper presented at the 16th
International Congress of Aviation and Space Med-
icine, Libson, 1967; ——, “On secondary influences
on circadian kidney function.” ibid.

T. Sasaki, Proc. Soc. Exp. Biol. Med. 115, 1129
(1964).

A. Kravrsov (chief of the Medical Sanitary Admin-
istration of the U.S.S.R.), official letter from the


patterns were given. Differing techniques were
cited, including tests with a new drug, flurazepam
hydrochloride, which, unlike most hypnotics, is
reported to induce sleep with no adverse effect on
the rapid-eye movement (REM) phase of sleep
now known to be essential to optimum mood and
efficiency during wakefulness; (see also Kleit-
man’s classical work*t). Pilots have reported
many informal means of inducing sleep between
ttights, including moderate exercise (walking)
and warm baths.

Tl.

The scientific literature of many countries re-
ports circadian rhythms which influence the be-
havior of biological systems. In the modern avia-/
tion environment man is exposed rather abruptly
to disruptions of these rhythms, particularly
during long east-to-west and west-to-east flights.
It is still an open question whether eastward or
westward flights from the point of origin pose a
higher stress on the air traveler.

Experimental evidence obtained on animals
and. man is still inconclusive; in the case of man,
the individual differences between “early risers”
and “early sleepers” may mask to some extent.
the transmeridianal time-shift effect. As to the
_ latitudinal displacements, the flight experiments
conducted so far did not last long enough to de-

Conclusions

termine whether pronounced shifts of the light-
dark ratio would affect the circadian oscillator.
In any case, the methods of lessening the effects
of desynchronization of circadian periodicities are
similar to those that are used for crew members
and travelers on long-distance flights. They spe-
cifically include the following:

(1.) Keeping the clock time and the environ-
mental factors at the destination the “same” as.
those at the point of origin through simulation
(this approach is often not practical, for obvious
reasons).

(2.) Scheduling flight time and rest time ac-
cording to a formula that takes into account the
number of time zones traversed, departure time,
state of rest at time of departure, and arrival
time, so that there is as much rephasing of the
critical circadian rhythms as is felt necessary in
the light of demands made on the individual be-
fore, during, and after the trip.

(3.) Pacing activities during the initial period
of rephasing so that superimposed stress (in par-
ticular, heavy eating and drinking )are kept to a
minimum. .

(4.) To avoid the necessity of taking tradi-
tional hypnotics, with consequent loss of REM
sleep, inducing sleep by moderate exercise and a
warm bath.



had a disturbing effect upon their preflight con-
dition. It took these disturbances longer to dis-
appear.

In the United States, experiments have been.
made by Federal Aviation Administration per-
sonnel on the effects of time-zone shifts on body
temperature, heart rate, respiratory rate, loss
of water by evaporation from the palms of the
hands, urinary output, reaction time, decision
time, and critical flicker fusion. Assessments
have been made of subjective fatigue, of subjec-
tive wellbeing, and of intellectual facility of trav-
elers before, during, and after intercontinental
flights in east-west, west-east, and north-south
directions, It was found that rectal-temper-
ature cycles adjusted to local time in 8 to 5 days
after a flight from Oklahoma City to Tokyo, and
readjusted to normal in 1 day after the return
to Oklahoma City. Reaction time, decision-mak-
ing time, and subjective fatigue scores were ad-
versely affected during the transition period in
Tokyo and, to a lesser degree, shortly after the
return to the point of origin. The differences
among individuals were found to be marked. In
a second east-west journey, from Oklahoma City
to Manila, phase shifts occurred in rectal temper-
ature and heart rate (in 4 days) and in evapora-
tive water loss (in 8 days). As for the psy-
chological functions, reaction time and subjective
fatigue were significantly increased in Manila,
but, in contrast to the time lags of the physiologic
phase shifts, the duration of these psychologic
effects was very short. By the second day fol-
lowing the arrival in Manila, normal psychologic
functions had apparently been restored. The re-
turn to Oklahoma City caused less transitory im-
pairment of the physiologic and psychologic fune-
tions.

A flight from Oklahoma City to Rome was
made to investigate possible bidirectional dif-
ferences in phase shift. The time lags of the pri-
mary shifts were greater than those associated
with the flight from Oklahoma City to Manila—
namely, 6 days for rectal temperature, 8 days
for heart rate, and even longer for evaporative
water loss. While the phase shifts that occurred
in Manila maintained the relations of the original
cycles, those that occurred in Rome were unre-
lated. In contrast to the physiologic functions
tested on the Rome trip, the psychomotor func-
tions tested showed no impairment after the west-
east translocation. However, there was significant

increase in subjective fatigue. After the return
from Rome to Oklahoma City, the rectal-temper-
ature and heart-rate cycles did not completely re-
adjust during the 5-day post-flight test period.
During the north-south flights, only subjective
fatigue showed a significant increase.

Similar results, in regard to the physiologic
phase shifts, were obtained in experiments by
Halberg®®. Cycles of sleep-wakefulness, oral tem-
perature, and renal excretion of 17-OH cortico-
steroids, 17-corticosteroids, sodium, and potas-
sium were studied in a healthy human subject
during a 12-day stay in isolation before departure
for Europe by air. Data were obtained during
the subject’s stay overseas and during 56 days of
isolation after his return to the United States.
The six cycles became desynchronized during the
subject’s isolation, and the phase shifts were found
to occur more slowly after west-east than after
east-west dislocation. The latter phenomenon was

uw TIME OF DAY
B2
to 24 6 l2 \s 24
ON Levees
aw
2 = <‘—SLEEP®> + WORK——® 4-RELAX->
F Lv. LY. (East)
w \
4 t
oO i]
2
3 1
a 1 |
< H '
Zz !
« I i
2 !
a \ '
1
!
ARR. ARR.
(East) (West)
8 It . 8 1
eu 1 1 24 6
28 Mri tris tert tri Ty
uN Work —p-<-rELax—pe—sieere
f
1
ro H
18 24 6 2 I
BS eerste My
N
= KR -RELAX—®<4-—SLEEP—»> + work——_»>

Figure 1. Representative diurnal curve such as might
be recorded for body temperature, heart rate, activity,
and other cycles. (Scale at top) Time of day for the
time zone to which the individual is adapted; (scale im-
mediately below curve) the corresponding time of day
seven time zones to the east of the zone to which the
individual is adapted; (scale at bottom) the corres-
ponding time of day seven time zones to the west of
the zone to which the individual is adapted (see text).


either environmental factors, such as light or
darkness, temperature, and tidal and other geo-
physical forces, or regularly repeated physiologic
processes such as going to sleep, eating, exerting
body wastes, and so on. Changes in the hours of
daylight and variations in environmental tem-
perature are the most effective time-givers*.
\/ Periodicities such as the diurnal cycles of light
and temperature do not force an oscillation on the
living system but “entrain” an oscillation. Un-
der normal conditions the time-givers play the
role of regulators by keeping the frequencies or
oscillations of the organism in step with the ex-
ternal stimuli. It is well known that the daily
J/fluctuations of physiological and_ psychological
functions show maxima and minima at certain
times of the 24-hour day. This is of practical
importance since there is evidence that these
/ rhythms are associated with temporal fluctuations
in efficiency and performance. For example, it
is known that there are diurnal variations in ef-
ficiency in the performance of various types of
tasks, such as sentry duty, automobile driving,
~ vadar observation, problem solving of all kinds,
and other mental and psycho-motor tasks*.
J Investigations of circadian rhythms have dem-
onstrated that the biological clockwork is com-
posed of a multitude of oscillating subsystems,
which are properly timed through mutual cou-
vPpling. If the system is uncoupled from the time-
giver or if the subsystems become asynchronous,
the internal clock imprecisely times the functions
and the periods may vary from 20 to 28 hours.
However, the functions can then become locked
upon another periodic system. This is the case
when an individual adapts to a somewhat different
timetable—for example, from normal time to day-
light saving time or to another local time during
travel. Since a natural day has two different
phases—the light period and the dark period—
which, outside the tropi¢s, may differ considerably
in length, especially at high latitudes, animals
migrating from north to south and vice versa
have to make adjustments to changes in the light-
dark ratio. The markedly affects their activity
pattern. When the time-givers, such as the light-
dark or the temperature phase, are modified, the
organism does not immediately follow the new
pattern; it may not do so for a few days or
even weeks, If the exogenous and endogenous
periods are similar, the entrainment process ad-
justs the inner clock to the environmental cycle

by establishing a definite phase relation between
the oscillations of the organism and the exogenous
periodicity’. We know, of course, that not all
biological functions have a 24-hour cycle, and,
furthermore, we know that the phase of biological
periodicities can be modified or resynchronized.
However, there are still many unsolved problems
concerning the application of the theoretical

(/ “models” to practical life situations; the limits

of permissible phase shifts; the changes associated.
with the direction of geographical dislocations;
and the interactions between time-givers and ac-
tivity patterns. Also, the medical implications of

~ desynchronization of the circadian system have

not been fully assessed.
Effects of Shifts of Light-Dark Ratio

Some early observations of the effects of
changes of the light-dark ratio concerned the
physiological functions of workers on alternating
work shifts. In a recent study® the diurnal
rhythm of body temperature of workers on al-
ternating day and night shifts was recorded.
Body temperature usually shows a peak during
the day and a drop at night. While the body
temperature of these workers followed the normal
diurnal time course during the 1-week day shift,
during the 5-week night shift it showed a dif-
ferent pattern at times of work or sleep, but, for
the time between 4 and 10 p.m., which was a
period of leisure on both shifts, it showed a
pattern very similar to that for the day shift.
The three workers used as subjects in this study
responded quite differently to. the changes in
work shift. One individual adjusted almost im-
mediately to the switchover, in either direction,
whereas the second needed several days to make
the adjustment. The third man never adapted
completely to the night- -shift routine. This in-
dividual variation in ease of adapting to time
changes and in ease of establishing new habit
patterns has been observed many times.

Since the metabolic structure is closely related
to the temporal parameters which determine the
physiological-function cycle*, the diurnal varia-
tions in urinary excretion of the 17 ketogenic
steroids, the catecholamines, sodium, potassium,
calcium, and inorganic phosphate were measured
during artificial shifts of the day-night cycle.
The catecholamine rhythm and, in particular, the
adrenaline (epinephrine) cycle, which normally
shows a peak during ordinary daytime activity,




TIME-ZONE EFFECTS ON THE LONG DISTANCE AIR TRAVELER

I. INTRODUCTION

The main celestial events within our planetary
system occur at certain intervals, are repetitive
and periodic, and follow predictable time pat-
terns. Since the earth, moon, sun, and other celes-
tial bodies are connected by such basic and ubiqui-
tous phenomena as gravity and radiation, it seems
plausible to assume that the variations associated
with geophysical and diurnal cycles affect the
course of life processes. Well-known examples
of periodicities in our daily life are the day-night
cycle, the wake-sleep cycle, the work-rest cycle,
and the menstrual cycle. Certain physiological
cycles appear to depend, therefore, on an “internal
clock,” a more or less accurate biological mech-
anism.

Halberg in 1959 introduced the term circadian
(derived from the Latin circa dies) for a time
period which approximates 24 hours; thus circa-
dian means about the same thing as diurnal (di-
urnal is defined as “daily”). Although these
circadian periodicities has been known for sev-
eral centuries, only recently has research on the
temporal dependencies of biological systems be-
come systematic and “mission-oriented” *.

The adverse effects of unusual schedules on the
individual’s subjective and physical state is noted
in the Declaration of Independence and con-
stituted one of the colonists’ grievances against
King George III. This passage reads: “He has
called together legislative bodies at places un-
usual, uncomfortable, and distant . . . for the sole
purpose of fatiguing them. ...” People tradi-
tionally have been very sensitive to, and resistant
to, alterations in their cycles of sleep and wake-
fulness. Rural people have been inclined to main-
tain these cycles in phase with sunset and sunrise.
They tend to arise earlier in the summer, when
sunrise is earlier, than they do in the winter. The
first published suggestion that great economies
could be effected by instituting what was later to
be called “daylight saving time” appeared in
1784 in the Journal of Paris; the author was

Benjamin Franklin. From the fact that the sug-
gestion was not followed until the 20th century,
we see how the human being clings to his cus-
tomary sleep-wake cycle.

II. DISCUSSION
Time Zones

Prior to 18 November 1883, no standard time
zones existed’. Individual towns estimated noon
as best they could by trying to determine when
the sun was most directly overhead. Thus, each
town had its own time, and there were more
than 100 different time zones in the United States.
The state of Michigan had 27 time zones. The
US. railroads, needing a more uniform system as
a basis for establishing train schedules, led in the
informal adoption of four standard time zones,
in 1883. The United States, in the Standard
Time Act of March 19, 1918, gave legal sanction
to the railroads’ four-zone system.

Twenty-Four-Hour Physiological Cycles

The importance of the periodicity of the earth’s
rotation as a factor in the rhythm of biological
functions is demonstrated by the 24-hour varia-
tions manifested by most forms of terrestrial life.

/Two forms of biological periodicity have been dis-
tinguished: (1) An exogenous periodicity, which
exists as long as the environmental factors change
periodically, fading like a “damped oscillation”
when the environmental conditions are kept con-
stant, and (2) an endogenous periodicity, which
functions like a biological clock after a certain
time pattern has been established‘. In this second
form of periodicity the oscillation has its own
natural period. which depends on the organism;
the environment merely influences the frequency
of the phase.

v In exogenous periodicity the periodic changes
of the surroundings play the role of “Zeitgeber”
(“time-givers”), or clues and synchronizers to
which the organism responds. Time-savers can be



Qualified requesters may obtain Aviation Medical Reports from Defense Documentation
Center. The general pubuic may purchase from Clearinghouse for Federal Scientific
and Technical Information, U.S. Dept. of Commerce, Springfield, Va. 22151


80.

Ministry of Civil: Aviation U.S.S.R., to the U.S.
Federal Aviation Agency (1967).

G. T. Haury, in Life Sciences and Space Rescarch
(North-Holland, Amsterdam, 1967), vol. 5; —— and
T. Adams, in Circadian Clocks (North-Holland, Am-
sterdam, 1965) ; ——, Aerospace Med. 37, 668 (1966) ;
—, ibid, p. 1027; —, ibid, p. 1257; —, Fed.
Aviation Office Aviation Med. Rep. AM 65-16 (1965).
F, Harpers, W. NELson, W. Rune, 0. H. Scunrr,
Fed. Proc. 26, No. 2 (1967).

iL

31. F. Harnere, personal communication.

82, J. AscHorr, Ed. Life Sciences and Space Research
(North-Hollanad, Amsterdam, 1967); —— and R.
Wever, Z. Vergl. Physiol. 46, 115 (1968) ; J. Ascrorr,
U. Gerecke, R. Wever, Japan J. Physiol. (1967).

83, A. Kanes (Department of Psychiatry, University of
California, Los Angeles), personal communication.

34, N. Kuxrrman, Sleep and Wakefulness (Univ. of
Chicago Press, Chicago, 1963).