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REDUCTION OF THE EFFECTSOF PROLONGED STRESS
DURING A 13 WEEK STUDY USINGTHE DIETARY SUPPLEMENT beCALM’d™
BARBARA FERRELL, Ph.D.Department of Family Health Medicine Faculty
University of Texas Medical Branch at Galveston, Texas
LARY A. DORRINGTON, M.S.Clear Lake Intermediate School
Houston, Texas
ALBERT H. BIESER, M.S.Natural Neuro Nutrition, Inc.Seabrook, Texas 77586-1111
ABSTRACT
beCALM’d™, an amino acid, vitamin, and mineral formulation, was designed to restorecatecholaminergic, opioidergic, GABAergic, and serotonergic deficits observed in individualssuffering from long-term, moderate-to-high emotional stressors. The formulation was found to reducesignificantly (to very significantly) the variability of blood pressure, skin conductance, and perceivedstress of participants during a double-blind, placebo-controlled, cross-over study of public schooleducators, compared with controls. Each school day, during the 14 weeks of the study, each participantmeasured his or her Skin Conductance Level (SCL,) using an Autogen AT
64, blood pressure, using
a standard digital readout cuff. Each then recorded his or her stress level by responding to the question,“On a scale of 1 to 10, with 1 being no stress and 10 being the most stress you have ever experienced,how would you rate your stress level today?” The factors studied are commonly accepted as stressindicators and are well known to be directly related to harmful continual, low level norepinephrineadrenaline release. During the experimental phase of the study these indicators werevery significantlydiminished. The results thus suggest that beCALM’d may facilitate the availability of the opioids,GABA, and/or serotonin depleted by long term stress, thereby limiting the tissue and organdegradation associated with prolonged norepinephrine adrenalin release.
Research Report
DRAFT DOCUMENT
INTRODUCTION
In the 20th century continual, low level stress is a part of everyday life. Traffic jams, jobpressures, and difficulty with relationships all have become accepted as normal. [The human body,as it has developed over the millennia, reacts to these stressors in the same way in which men have,for all of recorded history, when preparing to escape from physical danger.] That is, when dangerpresents itself, the body begins to undergo physiological changes which prepare it for meeting athreat. Heart rate, circulation, oxygen and energy supplies, and metabolism all increase to allow usto defend ourselves or to escape from the threat. Body functions such as digestion, which serve nouseful purpose at the time, decrease. All of our resources are marshalled to either “fight or flee" fromthe enemy or danger.
The stressors, which are a part of life for modern man, are not quickly eliminated. When the bodyevokes this “stress reaction” for a prolonged period of time in response to long-term stressfulsituations, the result can be devastating to physical and psychological health. Stress has beenimplicated in heart disease, hypertension, ulcers, depression and numberous other diseases. Over30,000 studies have been reported in the last five years relating disease to stress. In fact, it has beenestimated that over 75% of all disease prevalent in western society is related to the activation of thestress mechanism, and that more than 66% of all visits to primary-care physicians are for stress-
STRESS
Low Opioids
Low GABA
High Norepinepherine
Adrenalin ReleaseAdrenalin Release
High Dopamine
Low Serotonin
Sense of UrgencySleeplessness
Adrenalin Release
Adrenalin Release
HypertensionCardiovascular DiseaseGastro-intestonal DiseaseAnd many others
Results In:
CausesHigh AlertnessMemory Enhancement
Anxiety
THE STRESS CYCLE
Figure 1
related disorders14.While the cause of stress varies from individual to individual, the changes which, take place in
the body when under stress, are similar from person to person. Researchers have found that stress
3
depletes neuroregulators from the endogenous opioid, GABA, and serotonin systems, with a relatedincrease in dopamine and norepinephrine release(1,2,3,5,13). The effects of such neuroregulatorchanges in causing a variety of diseases have been demonstrated in numerous scientific studiescompleted and reported during the last fifteen years. A common neurobiological pathway has beensuggested to underlie uncontrolled use of psychoactive agents including alcohol by activating theopioid-mediated mesolimbic catecholaminergic receptors to provide pleasure or relief from pain(3).
The Stress Cycle shown in Figure 1 is based upon Blum’s “Reward Cascade” Link(2) and isdescribed below. From this is shown the mechanism of continuing stress causing the interrelation-ship among the reward/punishment systems within the hypothalamus to form an unstable feedbackloop which continually releases unneeded adrenalin. The effects of this release are well known:
Stress causes the opioid (endorphin, enkephalin, etc.) levels to diminish. The loweropioid levels create a sense of urgency. The lowering of the opioids causes an increase indopamine levels and a decrease in GABA levels. This produces a combination of anxiety andalertness.
The lowering of the GABA levels causes the norepinepherine levels to increase andserotonin levels to decrease. The increase in norepinepherine causes adrenalin to be releasedand the reduction of serotonin makes sleep difficult to impossible. The increasednorepinepherine encourages a quick, emotional response and discourages slower, deliberate(logical) thinking.
The adrenalin release causes the heart to beat both faster and harder and causes redcorpuscle reserves to be placed in the blood stream. It causes energy sources and nutrientsto be diverted from functional organs such as the liver, the digestive tract, etc. for use by themuscles. This results in the person being able to make an almost super-human physicalresponse to the threat.
The serotonin reduction further modulates the opioids downward. Thus, the cyclerepeats with increasing intensity.
{An analogy is found when a speaker steps to a microphone and snaps his fingers to testit. This sound is amplified and then reproduced by the loud speakers. The reproductiontravels back to the microphone at the speed of sound. There, it is picked up and re-amplified.As this continues, a tone is heard which is so loud that the auditorium is made ineffectual bythe very system designed to make it usable. The situation is brought under control by thespeaker turning down the amplifier’s gain control. When he does so, the system is able to dowhat it is designed to do.}
This understanding of the neurochemistry(9,10) led us to investigate the effectiveness ofrestoring brain neuroregulator balance in individuals experiencing stress levels known tocause neuroregulator imbalance.
Treatment of diseases resulting from the continual release of adrenalin caused by long term stress.
Traditional treatment for the patient suffering from the effects of long term emotional stress hastended to focus on three steps: 1) recovery from the damage already done (through the use of specificdrugs and nutritional supplementation); 2) making the patient more comfortable (through the use ofmood elevators such as vitamin B12 and B3, niacin): and 3) preventing further damage (throughbehavior modification techniques and stressor elimination when possible).
Studies have shown(1,2,3) that human design has the means of automatically “turning down thegain.” However, when stress is long term in nature, the metabolites needed for this action are depletedand ultimately the adjustment can no longer be made. Additional nutrition is required to replace thesemetabolites. While the quantities vary from one individual to another, getting these additionalnutrients from food is difficult. The average person would require several pounds of exotic fish, aquart of milk, and a variety of other high cholesterol and high fat content foods daily. A betteralternative is to consume the required additional nutrients as supplements.
A nutritional supplement (beCALM'd) has been formulated, as shown in Table 1. on thefollowing page, to relieve stress by introducing d/l-phenylalanine and l-glutamine which incombination with a formulation of vitamins and minerals has been shown to enhance opioids,GABA, and serotonin availability(1). This study was designed to test the ability of beCALM’d toenable the human to withstand a great deal of constant stress without suffering the effects attributedto continual norepinephrine adrenalin release.
4
THE FORMULATION
TABLE 1: The ingredients per capsule and their effects are as follows:
Restorative ExpectedIngredient Amount Action Mechanism Behavioral
Change
d/l-Phenylalanine 400 mg Enkephalin (d) Enzyme inhibition Reduced urgencyDopamine (l) Precursor loading Alertness
l-Glutamine 50 mg GABA up which Precursor loading Antianxiety reduceses Norepinephrine Antistress
Vitamin A 1000 IU Membrane Supplemental General bodyMaintenance Anti-oxidant repair
Vitamin B6 1 mg Pyridoxal-5- Promotes absorption FacilitatesPhosphate of amino acids action of
neuroregulators
Calcium 50 mg Serotonin Serotonin production EnhancedMagnesium 25 mg catalysts Sleep
Chromium 0.01 mg l-tryptophan Accelerate absorption of EnhancedPicolinate amino acids by muscles Sleep
thus reducing l-tryptophan competition at blood-brain barrier
The LD50 of d-phenylalanine (DPA) in rodents is 5,452 mg/kg. For a standard human male this toxicity level
translates, on a weight basis, to an LD50 of 436,160 mg. Allowing for a six fold difference in metabolically active body
mass between mouse and human(4), this equates to a projected LD50 in humans of 908.5 mg/kg or 72,693 mg. No toxic
effects were seen following acute administration of DPA to monkeys of 3000 mg/kg or chronic administration of 1000mg/kg/day for 30 days(6). Heller(8) has reported no toxic effects in rodents after two continuous years of dosagesequating to 1000 mg/kg/day. The LD
50 of l-phenylalanine in rodents is 5,287 mg/kg, and the LD
50 of l-glutamine in rodents
is 1,600 mg/kg.
These ingredients comprise a nutritional supplement known as beCALM’d (patent pending), manufactured byNatural Neuro Nutrition, Inc., Seabrook, Texas. (1-800-232-7563)
To test the formula a double-blind, placebo-controlled, crossover study was conducted in a suburban middle schoolin Houston, Texas. Educators were selected because they are representative of a large number of U.S. citizens in thatthey experence nearly continual moderate stressors and occasional moments of high level stress(14).
5
SUBJECTS AND METHOD
Group Selection and Dosage Regimen
Forty-seven public middle school educators consisting of teachers, administrators, and supportpersonnel volunteered for the study. Each participant was randomly assigned an identificationnumber and assigned to Group I (placebo-experimental) or to Group II (experimental-placebo). Theparticipants had no knowledge of their group assignments.
After one week of baseline measurements, participants om Group I received a numbered bottlecontaining capsules of the placebo, vitamin A with inert fillers, while participants in Group IIreceived capsules of theexperimental beCALM’d. The participants were instructed to take twocapsules before breakfast and two capsules before bedtime for 42 days. After a seven day cross-overperiod during which no capsules were taken (Spring Break for the educators), Group I was given a42 day supply of the experimental and Group II of the control. There were 14 subjects who withdrewwithdrew within the first two weeks of the test. Group I then contained 18 and Group II, 15. As thestudy was full cross-over in design this gave a resultant "n" of 33, more than sufficient for this typeof test(15).
Test Measurements
The time of day for taking measurements was left to the individual educator with the requirementthat it was to be the same time each day. Most chose their conference period. One selectedimmediately after school.
Cardiovascular Measurements: Standard systolic and diastolic blood pressure measure-ments were taken by the participants, using a BMS model 11-780 Oscillometric Unit, and recordeddaily throughout the study.
Skin Conductance Level (SCL): The electrical properties of the skin have been widely utilizedas an indirect measure of an individual’s stress level. Early lie detectors used only this measurement.A correlation exists between increased skin conductance and sympathetic activation of anxiety andorienting responses to stress. Therefore, a decrease in conductance is associated with a decrease inan individual’s autonomic response to stress (5,11,12). To obtain these measurements, an Autogen,Inc., model AT
64 , was attached to the middle two fingers of the dominant hand of each participant,
and a daily skin conductance reading was displayed and recorded by the participant.
Perceived Stress Level: Participants were asked to record their perceived stress level byresponding to the question “On a scale of 1 to 10, with 1 being no stress and 10 being the most stressyou have ever experienced, how would you rate your stress level today?”, and to circle their responseon a 1 to 10 scale on that day’s data sheet.
6
Method of Statistical Analysis:
TABLE 2. Means and standard deviations of baseline period:
Test (Group) Mean Standard Deviation
Diastolic (I) 75.00 5.20Diastolic (II) 72.29 5.46
Systolic (I) 117.57 6.04Systolic (II) 116.86 7.92
SCL (I) 2.20 0.77SCL (II) 2.03 0.47
Perc’d (I) 5.50 1.52Perc’d (II) 4.91 1.35
Examination of the baseline data (Table 1) revealed that the two groups did not differ in mean score or variabliltyon any of the measures.
Neuroregulator imbalance may allow wide variability in blood pressure, skin conductance, and perception ofstress. The prolonged variability of these factors by continual norepinephrine adrenalin release may account for the organand tissue damage associated with long-term stress(15). Therefore the data were analyzed to test the hypothesis thatsubjects would have less variation in blood pressure, skin conductance and percieved stress level when taking beCALM'dthan when taking placebo.
In this case a variance for each test half, placebo and experimental, was derived for each subject. Thecombination of each half was then evaluated on an “F33/30” distribution basis. The individual means, S2’s, group “F”scores, and final “F” score(Table 3) for each test are shown in Tables 4 & 5, (”F” Score Calculations). The group scoresare only relatively significant. Each of the final scores indicate significance (probability of error less than .05) with valuesof 1.84 or higher, and are deemed to be very significant (probability of error less than .01) with values of 2.39 or higher.
TABLE 3The final “F” scores for each test:
Diastolic 2.20Systolic 2.92Skin Conductance Level 2.58Perceived Stress Level 3.50
RESULTS
General
The environmental stress level in the school was typical during the week of the baseline measurements. It went uphighly during the first six weeks portion of the test. During this time a property tax roll-back election was passed, whicheffectively eliminated 18% of the school district’s budget for the next three years. In addition the district received noticeof a 6.5 million dollar reduction in state funding due to court mandated equalization of state funding of public schools.Each educator was very concerned that he or she might experience severe program cuts, salary reduction, or even lossof employment. By the time the final six weeks portion of the study began, most of the study’s participants had regained
7
their confidence in future job security. However, this period coincided with the ending of the schoolyear causing the stress level to be moderately higher than the baseline period.
This extreme variation in the ambient stress may have increased the variance in the Group Iplacebo period and the variance in the Group II experimental period. This tends to be supported bycomparison of the baseline and placebo results, and the statistical findings for each group. In the firstcase the results tend to indicate a greater population difference and in the second a lesser difference.However, the demonstrated baseline singularity of population of the two groups and the full cross-over nature of the study gives an overall effect of a more conservative test.
Blood Pressure
As demonstrated above, some of the most damaging effects of continued stressful events are therapid swings in blood pressure that accompany continuing moderate to high levels of emotionalstress. These effects are usually observable by monitoring blood pressure. The “F” ScoreCalculations sheet shows each subject’s diastolic and systolic blood pressure 30 day mean and 30 day“S^2” (sum or the square of variances from subject’s mean for each period.) The 33 S^2’s for thecombined placebo and experimental groups were then evaluated using the F Score ANOVA technic.Interestingly, while the diastolic test showed the results to be significant (probability of error less than5%), the systolic test showed the results to be highly significant (probability of error less than 1%).
Examples of diastolic data for typical subjects from both group are shown in Figures 2 through5. Subject No. 10’s results for Systolic (blood pressure), Skin Conductance Level , and PerceivedStress are shown for comparative purposes in Figures 6 through 9.
Skin Conductance Level
As stress levels go up, blood vessels in the extremities (e.g. finger tips) are constricted. Thiscauses two well known effects: a) skin temperature of extremities goes down and b) skin conductancefrom one extremity to another (even between adjacent finger tips) goes down. The later effect is oftenoffset by the presence of sweat on the skin. To counter this effect, electrolytic gel is often used onthe probes.
In this test the gel was not used as the tests were taken inside an air conditioned building, andstress significant enough to cause the subjects to break out into a cold sweat was not expected.Comments from the experimenters and subjects during the test indicated this was probably thecorrect decision.
8
Perceived Stress
The perception of being under emotional stress is usually not felt in time of fight or flee situations.It is felt heavily afterwards. In continuing stress, however, it is felt continually. The usual symptomsare frustration, fatigue, short temper and in extreme cases, periodic short sighs. These are oftenaccompanied by the desire to eat and/or to drink alcohol excessively.
Thus, in the case of long term stress the perception of stress is usually agood gauge ofenvironmental stress levels.
CONCLUSION
The results of the study show a very significant reduction in four of the most common stress effectindicators. Based upon Blum's well established "Reward Cascade," these results suggest thatbeCALM'd facilitates the availability of the opioids, GABA, and/or serotonin depleted by long-termstress, thereby limiting or eliminating norepinephrine adrenalin release except in fight or fleeincidents . Such a result is expected to significantly diminish the tissue and organ degradation andother related diseases associated with long-term stress (see National Library of Medicine for over20,000 recent references.)
ACKNOWLEDGEMENT
The authors would like to thank C. E. Peter Clarke, M.D., Houston, Texas, for the invaluablemedical knowledge and insights he contributed to this study.
9
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6.0
04
10
.00
11
1.2
17
2.5
01
13
.89
68
.07
1.4
6E
+0
24
.88
E+
02
77
.25
8.6
96
8.2
91
7.6
56
9.1
72
9.0
83
.66
E+
02
9.1
0E
+0
01
17
.00
36
.50
10
7.1
82
9.9
31
10
.86
55
.31
9.3
0E
+0
28
.72
E+
01
86
.67
1.5
68
2.6
14
8.4
67
9.1
92
9.2
61
.37
E+
02
8.0
3E
+0
01
34
.67
13
.56
12
9.3
97
0.3
31
26
.81
60
.77
9.7
8E
+0
12
.19
E+
02
69
.60
10
9.4
46
5.1
75
8.6
36
7.2
18
2.5
34
.77
E+
02
2.5
4E
+0
31
12
.20
67
.36
10
3.0
04
8.4
81
07
.62
48
.34
1.4
3E
+0
25
.62
E+
00
69
.20
33
.36
70
.03
36
.93
69
.39
48
.05
2.2
3E
-02
2.5
5E
+0
21
15
.20
18
.56
10
7.3
86
6.8
61
07
.17
48
.80
4.1
2E
+0
17
.97
E+
00
65
.40
19
.04
62
.93
19
.37
64
.43
31
.24
3.0
3E
+0
27
.19
E-0
11
09
.40
15
6.2
41
00
.15
17
.68
10
4.2
52
8.5
81
.83
E+
03
3.0
2E
+0
26
7.0
00
.00
84
.20
6.4
68
5.5
01
1.7
59
.20
E+
02
4.1
4E
+0
21
37
.00
0.0
01
31
.50
10
3.1
51
31
.55
33
.35
1.8
2E
+0
31
.59
E+
02
79
.50
0.2
57
1.2
92
4.8
27
0.3
52
9.2
11
.43
E+
02
8.3
1E
+0
01
20
.00
4.0
01
14
.75
72
.47
12
0.3
52
7.7
81
.45
E+
02
3.3
1E
+0
27
6.0
04
1.2
07
2.8
01
3.4
66
8.6
81
8.0
35
.44
E+
02
1.9
8E
+0
21
16
.80
48
.56
10
6.7
96
3.7
41
07
.05
41
.01
1.0
9E
+0
12
.46
E+
01
72
.33
72
.22
73
.59
37
.31
70
.90
46
.42
2.8
5E
-01
2.0
5E
+0
21
18
.67
17
.56
11
5.5
95
8.1
21
18
.62
48
.90
5.3
3E
+0
08
.56
E+
00
73
.25
23
.69
74
.46
21
.84
77
.00
15
.07
2.2
3E
+0
22
.90
E+
02
12
5.2
53
8.6
91
17
.77
78
.79
12
1.1
97
2.6
53
.37
E+
02
7.1
1E
+0
27
4.6
01
6.2
47
1.4
02
8.1
87
2.7
42
9.9
07
.40
E+
01
4.8
1E
+0
01
12
.60
53
.04
10
8.3
32
6.2
91
10
.96
28
.28
1.1
7E
+0
33
.13
E+
02
72
.29
71
.76
71
.28
11
6.8
61
11
.75
11
3.3
72
9.8
33
6.7
83
2.0
96
2.8
06
0.4
34
5.9
7
2.2
02
.92
"F
" Sc
ores
: abo
ve 1
.84
sign
ify
p =
.05
or le
ss; a
bove
2.3
9, p
= .0
1 or
less
T
able
4.
No
.G
rp1
12
17
11
01
13
11
41
16
11
91
20
12
21
23
12
51
26
13
21
47
14
81
49
15
01
Mea
n of
Mea
ns
Mea
n of
S^2
32
42
21
22
42
30
23
52
36
23
72
38
23
92
40
24
12
44
24
52
46
2
Mea
n O
f Mea
nsM
ean
of S
^2
F s
core
"F"
Scor
e C
alcu
lati
ons
Ski
n C
ondu
ctan
ce L
evel
P
erce
ived
Str
ess
Leve
lB
ase
line
Pla
ceb
oE
xper
im
en
tal
Var
ian
ceB
ase
line
Pla
ceb
oE
xper
im
en
tal
Var
ian
ceS
CL
Mea
nS
CL
S^2
SC
L M
ean
SC
L S
^2S
CL
Mea
nS
CL
S^2
Pla
cebo
Exp
Pcv
d M
ean
Pcv
d S
^2P
cvd
Mea
nP
cvd
S^2
Pcv
d M
ean
Pcv
d S
^2P
lace
boE
xp1
.24
0.0
70
.81
0.1
30
.75
0.0
92
.93
E-0
22
.86
E-0
12
.40
0.2
43
.37
0.9
71
.73
0.8
62
.75
E+
00
1.8
0E
-01
2.6
50
.17
1.8
80
.42
1.2
40
.66
1.3
9E
-02
1.1
8E
-03
2.6
70
.22
3.5
51
.35
2.3
81
.01
1.6
5E
+0
07
.87
E-0
22
.42
0.0
52
.73
0.4
02
.13
1.2
98
.83
E-0
34
.44
E-0
15
.00
3.2
07
.44
0.7
77
.16
0.6
93
.49
E+
00
3.5
0E
-01
1.7
00
.21
1.4
70
.29
0.8
90
.46
3.0
1E
-04
2.6
9E
-02
6.0
02
.00
4.3
53
.76
2.0
60
.61
1.2
7E
+0
04
.60
E-0
11
.44
0.0
91
.08
0.1
00
.72
0.1
74
.23
E-0
22
.09
E-0
16
.00
0.8
06
.31
1.0
66
.70
1.6
12
.48
E+
00
1.0
5E
-01
3.7
81
.30
3.2
90
.63
2.3
21
.69
1.0
8E
-01
1.1
4E
+0
05
.20
4.5
64
.25
3.6
94
.96
1.7
11
.11
E+
00
1.7
7E
-01
2.7
25
.09
1.7
70
.23
0.8
11
.00
5.5
8E
-03
1.4
3E
-01
6.7
50
.19
4.7
32
.47
2.2
41
.42
2.6
2E
-02
1.7
7E
-02
1.4
20
.20
0.9
60
.07
0.7
30
.13
5.5
9E
-02
2.4
4E
-01
3.8
05
.76
3.2
63
.84
1.4
40
.25
1.4
7E
+0
01
.07
E+
00
1.8
40
.06
1.4
80
.24
1.3
40
.16
4.5
9E
-03
2.1
6E
-01
8.0
03
.50
4.0
03
.60
3.2
10
.50
9.3
5E
-01
6.2
1E
-01
0.8
80
.03
1.0
10
.09
0.6
70
.16
4.6
5E
-02
2.1
9E
-01
6.6
71
.56
5.4
43
.75
6.1
01
.90
1.2
4E
+0
03
.71
E-0
12
.60
0.5
71
.28
0.1
80
.79
0.2
71
.45
E-0
21
.27
E-0
16
.50
3.2
54
.69
1.4
43
.33
1.5
61
.41
E+
00
7.2
5E
-02
1.1
40
.06
0.7
00
.12
0.6
00
.13
3.3
0E
-02
2.4
0E
-01
8.0
04
.00
4.1
94
.78
3.4
41
.80
4.6
0E
+0
02
.66
E-0
11
.87
0.1
01
.67
0.0
91
.23
0.4
24
.52
E-0
24
.23
E-0
26
.00
2.0
07
.32
1.7
66
.38
2.0
77
.58
E-0
16
.10
E-0
12
.42
0.0
71
.95
0.2
00
.99
1.0
29
.93
E-0
31
.59
E-0
16
.00
0.8
06
.13
0.3
75
.92
0.3
35
.10
E+
00
9.2
2E
-01
2.6
31
.91
1.2
90
.59
0.7
50
.39
7.9
7E
-02
5.5
2E
-02
6.5
02
.25
3.5
91
.54
1.4
60
.25
1.2
0E
+0
01
.08
E+
00
2.9
40
.61
1.8
40
.21
1.2
60
.51
8.8
8E
-03
1.3
2E
-02
3.0
00
.50
3.3
91
.02
2.5
71
.03
2.6
0E
+0
06
.66
E-0
23
.28
0.0
43
.29
1.2
21
.94
2.4
88
.42
E-0
13
.43
E+
00
5.8
03
.76
5.9
47
.16
4.4
22
.66
2.0
5E
+0
11
.89
E+
00
2.6
30
.18
1.9
10
.26
1.7
60
.21
1.8
9E
-03
1.7
1E
-01
4.6
72
.89
4.7
84
.06
3.5
32
.92
2.0
4E
+0
02
.65
E+
00
2.2
01
.69
1.1
65
.50
4.8
23
.83
0.6
00
.30
0.6
22
.30
2.6
31
.29
1.1
20
.04
0.8
10
.16
1.0
90
.09
9.9
3E
-02
4.0
4E
-02
6.4
03
.04
4.7
56
.71
6.9
22
.35
2.1
6E
+0
17
.97
E-0
12
.30
0.4
20
.91
0.7
11
.72
0.1
95
.27
E-0
29
.87
E-0
35
.50
6.2
55
.13
2.8
83
.82
2.8
66
.62
E-0
11
.95
E+
00
1.9
60
.19
2.6
80
.53
2.2
10
.21
2.4
7E
-03
6.5
2E
-03
4.4
01
.84
6.1
31
.56
2.7
11
.52
2.5
1E
-01
2.9
4E
-03
1.7
00
.16
1.3
70
.60
2.0
10
.42
1.3
8E
-02
1.7
1E
-02
3.7
50
.19
4.4
21
.03
4.5
70
.49
1.0
6E
+0
09
.38
E-0
12
.00
0.3
00
.93
0.2
91
.34
0.2
33
.56
E-0
23
.65
E-0
32
.25
0.1
92
.79
1.2
43
.21
0.9
56
.76
E-0
12
.57
E-0
13
.13
0.4
41
.62
0.4
82
.21
0.4
05
.44
E-0
61
.34
E-0
27
.33
2.8
91
.50
0.0
01
.94
0.0
04
.25
E+
00
2.1
4E
+0
02
.26
0.2
61
.30
0.5
41
.98
0.2
14
.38
E-0
36
.72
E-0
33
.00
0.8
03
.68
0.9
43
.93
0.5
81
.25
E+
00
7.8
5E
-01
0.9
60
.03
0.7
10
.05
0.7
70
.02
1.8
6E
-01
7.1
9E
-02
4.4
02
.24
5.6
12
.08
6.2
31
.74
5.0
5E
-04
7.6
8E
-02
1.4
60
.05
0.6
40
.13
0.8
60
.04
1.1
8E
-01
6.2
0E
-02
6.4
02
.64
3.9
61
.04
4.3
31
.81
1.0
5E
+0
01
.24
E-0
13
.00
0.0
01
.66
1.0
92
.54
0.6
93
.76
E-0
11
.59
E-0
18
.00
0.0
03
.43
1.7
36
.22
0.8
21
.11
E-0
14
.16
E-0
1
2.6
50
.06
0.9
21
.15
1.9
40
.64
4.5
7E
-01
1.2
7E
-01
4.5
00
.25
3.7
02
.78
4.1
34
.28
5.1
0E
-01
7.9
6E
+0
00
.90
0.0
50
.55
0.0
60
.59
0.0
71
.77
E-0
14
.99
E-0
22
.80
0.5
62
.43
0.7
33
.19
0.5
31
.79
E+
00
8.6
6E
-01
2.6
70
.27
2.2
60
.66
2.8
40
.49
3.2
0E
-02
3.8
5E
-02
6.3
30
.89
3.5
05
.00
5.0
01
.14
8.6
3E
+0
01
.04
E-0
11
.53
0.0
30
.92
0.0
91
.14
0.0
31
.53
E-0
16
.72
E-0
25
.00
4.5
04
.00
1.8
34
.24
1.8
35
.53
E-0
21
.38
E-0
12
.78
0.9
11
.42
0.6
42
.03
0.6
12
.60
E-0
21
.06
E-0
13
.60
1.0
42
.64
1.3
92
.67
1.0
24
.53
E-0
11
.99
E-0
1
2.0
31
.25
1.6
84
.91
4.1
24
.21
0.2
10
.48
0.2
91
.82
2.0
61
.46
2.5
83
.50
"F"
Sco
res:
abo
ve 1
.84
sign
ify
p =
.05
or le
ss; a
bove
2.3
9, p
= .0
1 or
less
Tab
le 5
The Following Charts Are Given
To Graphically Demonstrate
The Results Of This Study
55
60
65
70
75
80
85
90
95
10
0 -1
0-
50
51
01
52
02
53
03
54
04
55
05
56
0D
ay
Dia
stol
ic M
easu
rem
ents
of
Sub
ject
No.
20
Bas
eLi
neP
lace
bo P
erio
dE
xper
imen
tal
Per
iod
Mea
n
Mea
nM
ean
Fig
ure
4.
S2
= 3
9.20
S2 =
22.
69S2
= 4
4.24
90
95
10
0
10
5
11
0
11
5
12
0 -10
-5
05
10
15
20
25
30
35
40
45
50
55
60
Da
y
Sys
tolic
M
easu
rem
ents
of
Sub
ject
No.
20
Bas
eLi
neP
lace
bo P
erio
dE
xper
imen
tal
Per
iod
Mea
nM
ean
Mea
n
Fig
ure
7
S2
= 7
.42
S2 =
4.4
8S2
= 7
.77
123456789
10
11 -1
0-
50
51
01
52
02
53
03
54
04
55
05
56
0D
ay
Per
ceiv
ed S
tres
sors
of
Sub
ject
No.
20
Bas
eLi
neP
lace
bo P
erio
dE
xper
imen
tal
Per
iod
Mea
n
Mea
n
Mea
n
S2
= 1
.87
S2 =
0.7
1S2
= 1
.90
Fig
ure
10
60
65
70
75
80
85
90
95
10
0 -10
01
02
03
04
05
06
0D
ay
Dia
stol
ic M
easu
rem
ents
of
Sub
ject
No.
10
Bas
eLi
neP
lace
bo P
erio
dE
xper
imen
tal
Per
iod
Mea
nM
ean
Mea
n
Fig
ure
3
S2 =
19.5
0S2
= 2
1.38
S2 n
= 3
3.45
Sys
tolic
Mea
sure
men
ts o
f S
ubje
ct N
o. 1
0
Bas
eLi
neP
lace
bo P
erio
dE
xper
imen
tal
Per
iod
Mea
n
Mea
n
Mea
n
Fig
ure
6
S2 =
33.
68S2
= 2
17.5
8
11
0
12
0
13
0
14
0
15
0
16
0
17
0
18
0 -1
00
10
20
30
40
50
60
Da
y
S2
= 7
.50
0
.25.5
.751
1.2
5
1.5
1.7
52
2.2
5
2.5 -1
00
10
20
30
40
50
60
Da
y
SC
L M
easu
rem
ents
of
Sub
ject
No.
10
Bas
eLi
ne
S2 =
0.2
9S2
= 0
.46
Pla
cebo
Per
iod
Exp
erim
enta
l P
erio
d
Mea
n
Mea
n
Mea
n
Fig
ure
8.
S2
= 0
.21
Per
ceiv
ed S
tres
sors
of
Sub
ject
No.
10
Bas
eLi
neP
lace
bo P
erio
dE
xper
imen
tal
Per
iod
Mea
n
Mea
n
Mea
n
Fig
ure
9.
S2
= 2
.00
0123456789
10 -1
00
10
20
30
40
50
60
Da
y
S2 =
3.7
6S2
= 0
.61
Dia
stol
ic M
easu
rem
ents
of
Sub
ject
No.
21
Bas
eLi
ne
S2 =
47.
73S2
= 1
80.8
8
50
55
60
65
70
75
80
85
90
95
10
0
10
5
11
0 -10
-5
05
10
15
20
25
30
35
40
45
50
55
60
Da
y
Mea
n
Mea
n
Mea
n
Pla
cebo
Per
iod
Exp
erim
enta
l P
erio
d
Fig
ure
5
S2
= 1
2.56
Dia
stol
ic M
easu
rem
ents
of
Sub
ject
No.
1
Bas
eLi
neP
lace
bo P
erio
dE
xper
imen
tal
Per
iod
50
52
.555
57
.560
62
.565
67
.570
72
.575
77
.5 -10
01
02
03
04
05
06
0D
ay
Mea
n
Mea
nM
ean
Fig
ure
2
S2
= 1
0.16
S2 =
9.0
7S2
= 1
7.62
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