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Depression - A Beneficial Effect of Calcium Intake on Mood
A Beneficial Effect of Calcium Intake on
Mood
Kamyar Arasteh, Ph.D.
Journal of Orthomolecular
Medicine
Vol. 9, Number 4, 1994
Kamyar Arasteh, Ph.D.
Abstract
Two experiments were conducted to test the hypothesis
that the intake of supplementary calcium elevates mood. A total of 123 student
volunteers without a previous diagnosis of depressive disorders received either
placebo or calcium (1000 mg) tablets. The tablets were taken for a period of
four weeks, one tablet, twice per day. In Experiment 1. mood was assessed at two
times: Once before the start of calcium intake and another time after four weeks
of calcium intake, The supplementary intake of calcium, compared to placebo, was
associated with significantly greater elevation in mood as measured by the Beck
Depression Inventory. In Experiment 2, mood was assessed before, two weeks
after, and four weeks after calcium intake, as well as a fifth time, one week
after the discontinuation of calcium intake. As in the first experiment,
calcium, in contrast to placebo, produced a significantly greater elevation in
mood. The results of these experiments show a beneficial effect of calcium on
mood and suggest a possible use for the treatment of depressive
disorders.
It has been known for many decades that calcium plays an
important role in neuronal activity, and the list of neuronal processes found to
be mediated by calcium continues to grow. Because neuronal activity influences
cognitive and behavioural variables, the discoveries of the different neuronal
effects of calcium are of great significance to the sciences of mind and
behaviour. This is especially evident in the instances that calcium affects
neuronal processes specifically associated with particular mental or behavioural
phenomena. One such instance is represented by the finding that calcium
influences the activity of the neurons that are theorized to mediate mood.
Monoaminergic neurons have been theorized to mediate mood and emotions. There is
a variety of evidence that suggest the involvement of these neurons in mood and
emotions. Electrical stimulation of these pathways, for example, are associated
with the production of reward (Crow, Spear, & Arbuthnott, 1972; Gallistel,
Shizgal, & Yeomans, 1981; Stein, 1968). Pharmacological treatments that
increase monoaminergic activity produce an antidepressant effect (Goodwin,
Murphy, Brodie, & Bunney, 1970; Jouvent et al., 1977; van Praag, 1979;
Willner, 1983). Pharmacological treatments that decrease the activity of these
neurons produce a depressant effect (Fries, 1954; Randrup et al., 1975; Raskin,
Schulterbrandt, Reatig, & McKeon, 1970). Additionally, many antidepressants
have been shown to increase monoaminergic activity (e.g., See Carlsson, 1961;
McNeal & Cimbolic, 1986; Murphy et.al., 1981; Potter, Rudorfer, & Manji,
1991). Finally, in some subtypes of depressive illness monoaminergic activity is
reduced (Mass, Fawcett, & Dekirmenjian, 1972; van Praag, Korf, &Schur,
1973; Schildkraut, 1965; Sjostrom, 1973).
On the other hand, calcium has
been found to affect the activity of these neurons. Calcium-dependent
calmodulin, for example, increases the synthesis of monoamines (Kuhn &
Lovenberg, 1982). Large increases in the extracellular calcium have been
reported to dramatically decrease the activity of monoaminergic neurons (Trulson
& Crisp, 1985). Also, the release of the neurotransmitters depends on the
entry of calcium into the nerve terminal (Katz & Miledi, 1970), Moreover, it
is hypothesized that the postsynaptic effect of the monoamines is mediated by a
calcium-dependent mechanism (Phillis, 1974).
More direct evidence of
state for calcium in mood is also available. For instance, in animal models of
depression, large increases of calcium levels have been associated with
decreases in escape response (Trulson, Arasteh, & Ray, 1986), and the
administration of a calcium agonist has decreased mobility (Mogilnicka, Czyrak,
& Maj, 1988). Furthermore, Mogilnicka et al. (1998) were able to block the
effect by the administration of a calcium-channel blocker. In humans, some
conditions that are associated with changes in calcium metabolism (e.g.,
hypercalcemia and hyperparathyroidism) are also accompanied by changes in mood
(Cogan et at., 1978; Mandel, 1960; Reinfrank, 1961) and mood disorders are
associated with altered levels of intracellular calcium (Dubovsky, Murphy,
Thomas, & Rademacher, 1992). Finally, some studies have mooned successful
treatment of patients with bipolar depressive illness by using organic
calcium-channel blockers (e.g., Dubovsky, Franks, Lifschitz, & Coen, 1982;
Caillard et al., 1982; Garza-Trevifio, Overall, & Hollister,
1992).
These findings suggest that changes in calcium levels are closely
related to alterations in mood. Moreover, there appears to be a biphasic effect
such that slight increases in calcium levels seem to be associated with
improvement in mood, whereas very large Increases are associated with the
opposite effect.
The two studies presented here were conducted to provide
an experimental investigation of the effect of relatively small increases in
calcium levels over a period of four weeks. It was hypothesized that the intake
of dietary calcium supplement would result in an improvement in
mood.
Experiment 1
Method
Participants. Forty seven male and
female university students enrolled in the introductory psychology course were
recruited for the study in exchange for receiving credit towards the fulfilment
of their course requirements. Subjects did not have a history of calcium-related
disorders and were not taking calcium supplements prior to the study. They were
informed about the experimental procedures and their consent was
obtained.
Calcium Tablets. Calcium tablets were composed of 1000
mg of calcium and 600 IU of vitamin D. This amount of supplement has been shown
to be effective in producing cardiovascular change, perhaps due to the ability
to block calcium channels (McCarron, 1985; McCarron, Morris, & Cole, 1982).
The addition of vitamin D is necessary for the absorption of calcium from the
intestinal tract. Placebo tablets were similar to calcium tablets in appearance,
but were composed of gelatin and filler.
Measures. Two measures
were used in the assessment of mood: The BDI (Beck, 1978), and the Zang Self
Rating Depression Scale (SDS; Zang, 1965). The BDI consists of 21 items derived
from clinical observation, The possible scores an this measure range from 0 to
63. Scores of 9 of below are considered to be asymptomatic, and scores of 10 to
18 are considered to be associated with mild/ moderate depression (Beck and
Steer, 1987), Scores higher than 18 indicate severe depression. The SDS consists
of 20 items. The possible raw scores range from 20 to 80, and scores of 40 or
above are considered to be indicative of clinical
depression.
Design. A double-blind, factorial design with random
assignment of treatment levels was used. Subjects were divided into two mood
groups, "non-depressed," and "depressed" according to their initial BDI scores.
Subjects in each group were then randomly assigned to one of the two treatment
levels (i.e., placebo or calcium). Each subject was tested at two
times.
Procedure. The experiment was conducted in two sessions, At
the start of the first session, the participants received information about the
protocol and their consent was obtained, Subsequently, the BDI and SDS were
administered. The BDI scores of the participants were then used to divide them
into the two mood groups of "non-depressed" (BDI 9) and "depressed" (BDI 10),
These cut-off scores were used following the guidelines suggested by Beck and
Steer (1987). Using a random number table, the participants within each mood
group were then assigned to either the calcium or placebo groups (in keeping
with the double-blind nature of the experiment, scales, questionnaires, and
tablet vial of each individual were identified by ID numbers only). One day
after the first session, the participants were given a four-week supply of the
appropriate tablets in an unlabeled vial and were told to take one tablet, twice
per day over the following four weeks. After four weeks the BDI and the SDS were
administered again and the subjects were debriefed about the nature of the
experiment.
Results
Two dependent measures, BDI and SOS, were
calculated for each subject by subtracting their BDI and SDS scores of the first
session from those of the second session. Factors were calcium (i.e., whether
the subject had received calcium or placebo tablets) and mood (i.e.,
"non-depressed" when the subject had an initial BDI score of 9 or less, and
"depressed" when the subject had an initial BDI score of 10 or greater). Data
were analyzed by the SPSS procedure for ANOVA. There was a significant effect of
calcium on BDI (F (1, 33) = 4.58, p < .05). The mean decrease in the BDI
score of the calcium group was 3.05 (SD=2.39) in comparison to 1.33 (SD=3.12) of
the placebo group. These changes meant that the mean BDI score of the calcium
group, had changed from 5.47 (SD=3.27) to 2.42 (SD=2.59), while the mean BDI
score of the placebo group had changed from 6.06 (SD=4.21) to 4.72 (SD=3.88).
Also, there was a significant effect of mood (F(l, 33) = 9.07, p<.01) on BDI
The mean decrease in the BDI score of the "depressed" group was 4.29 (SD=4.07)
in contrast to 1.73 (SD=2.35) of the "non-depressed" group. However, there was
no interaction effect on BDI. Calcium did not have any significant effect on
SDS. However, the mean decrease in the SDS scores was greater for the calcium
group (X=2.73, SD=3.0) than for the placebo group (X=1.0, SD=6.45). Also, the
effect of mood on SDS approached significance (E (1, 33) = 3.07, p < A). The
mean decreases in the SDS scores were 1.07 (SD= 4.83) for the "non-depressed"
group and 4.43 (SD= 4.93) for the placebo group.
Experiment
2
Method
Participants. Seventy six male and female university students
enrolled in the introductory psychology course were recruited for the study in
exchange for receiving credit towards the fulfilment of their course
requirements. Subjects did not have a history of calcium-related disorders and
were not taking calcium supplements prior to the study. They were informed about
the experimental procedures and their consent was obtained.
Calcium
Tablets. The same tablets as in Experiment 1 were
used.
Measures. As in Experiment I the BDI was used. However SDS
was replaced with (he Depression Adjective Check List (DACL), which may be more
appropriate for measuring changes in mood in nonclinical populations. The DACL
is a list of 32 adjectives, 10 of which are associated with the absence of
depression and 22 of which are associated with depression. The possible scores
on this scale range from 0 to 34. Higher scores are associated with greater
severity of mood.
Design. Same design as in Experiment I was
implemented, with the exception that each subject was tested at four
times.
Procedure. The experiment consisted of four sessions.
Session procedures were similar to Experiment 1 and the same methods were used
to assign the subjects to groups. One day after the first session, the
participants were given a two-week supply of the appropriate tablets in an
unlabeled vial and were told to take one tablet, twice per day over the
following two weeks. Two weeks after the start of the experiment the
participants were again administered the BDI and DACL. At the end of the session
each participant received another vial containing a two-week supply of their
tablets, and the appropriate instructions. Four weeks after the start of the
experiment, the scales were administered a third time and the participants
discontinued their intake of the tablets. The scales were administered a final
time at five weeks, and at the end of the session the participants were
debriefed about the nature of the experiment.
Results
Two
dependent measures, BDI and DACL, were calculated for each session of each of
the subjects by subtracting the BDI and DACL scores of session I from those of
session 2, 3, and 4, Data were analyzed using the SPSS univariate procedure for
MANOVA with repeated measures. Calcium produced a significant overall difference
in the BDI (E (1, 47) = 4.47, p < .05). Several patterns in the data were
observed.
First, during the period of supplement in like, the mean decrease
in the BDI scores of the calcium group was 5.35 (SD=5.64) 'in contrast to 2.92
(SD=3.99) of the placebo group These changes meant that the mean BDI score of
the calcium group had changed from 9.65 (SD=7.07) to 3.31 (SD=3.11), while the
mean BDI score of the placebo group had changed from 7.96 (SD= 6.55) to 5.04
(SD=6.78). Moreover, during the same time period, the mean BDI score of the
"depressed" subjects in the calcium group changed from 17.0 (SD= 8.21) to 5.57
(SD= 3.41), a change of 11.43 points, while that of the "depressed" subjects in
the placebo group changed from 16.33 (SD= 8.55) to 12.33 (SD= 10.46), a change
of 4.0 points. In addition to the effect of calcium, mood produced a significant
difference in the BDI (E (1, 47) = 11 39, p < .005). For the duration of the
stud he mean decrease in the BDI score of the "depressed" group was 7.0
(SD=7.87) in contrast to 3.13 (SD= 2.88) for the "non-depressed" group.
Additionally, the interaction between calcium and mood produced a significant
effect in BDI Scores (F(1.47)= 4.76, p.<.05). However, the post-hoc analysis
did not show any significant difference between the group, at each session,
Calcium did not have any significant effect on the DACL. However he mean
decrease in the DACL scores Z greater for the calcium group (X=2.89, SD= 6.81)
than for the placebo group (X=I.I2, SD=6.54). No significant effect of mood was
observed for the DACL scores.
General Discussion
The results
of the two studies presented are consistent with the hypothesis that the intake
of supplemental dietary calcium can improve mood. In both studies calcium
significantly decreased the BDI scores, and the effect size was similar in both
studies. Moreover, in Experiment 2 the effect of calcium in the "depressed"
group was such that the ELI scores decreased from a mean of 17.00, which is
associated with moderate depression, to a mean of 5.57, which is well below the
cut-off score for mild depression. a This is in contrast to the placebo group,
in which the BDI scores decreased from a mean of 16.33 to 12.33, a score that is
associated with mild depression. In a clinical population, such a difference
will be important.
Although the changes in SDS and DACL scores were in
the direction predicted by the experimental hypothesis, calcium did not
significantly affect either SDS or DACL scores. It is possible that the scales
are less sensitive than the BDI to changes in mood, or at least to a subset of
changes in mood that may be induced by calcium, and therefore failed to register
these mood alterations. This possibility seems more plausible, because the BDI
is considered to be more sensitive to changes across time and drug treatment
trials (Mayer, 1977), However, the SDS items are very similar to the BDI items.
In both scales there are face valid items that are designed to assess 1)
depressed feeling, 2) hopelessness, 3) indecisiveness 4) dissatisfaction, 5)
suicidal ideation, 6) irritability, 7) weight loss, 8) loss of libido, 9) loss
of appetite, 10) sleep disturbance, 11) somatic preoccupation, 12) crying, and
13) fatigability. The BDI item, also include those that measure social
withdrawal, and body image changes, symptoms that are not directly assessed by
the SDS, The latter, on the other hand, includes items that measure confusion
and agitation, which are not directly measured by the BDI. Also, the proportion
of variance in one scale that is accounted for by the other is generally low
(Kerner Be Jacobs, 1983). The correlations reported for DACL and BDI are
generally of lower magnitude (Lubin, 1981) than those far SDS and BDI (Beck and
Steer, 1987). Although it is difficult to judge the apparent overlap of the DACL
and BDI, because of he superficial dissimilarity of the scales.
In
addition to answering the general question of whether calcium can improve mood,
he time course of the calcium effect was investigated in Experiment 2. However,
because at each specific session the differences between the calcium and placebo
groups did not reach significance, no conclusions could be drawn in this regard.
Therefore, the time course of the effect remains to be examined.
One
improvement can be made in future studies by monitoring the blood-level for
ionic calcium to provide both a measure of object compliance for the intake of
the supplements, and a covariate for the outcome measure. Also, the inclusion of
a waiting control group will be useful as an index for comparing the extent of
the effect of placebo with that of calcium.
Conclusion
It is
clear that if the results of this study are supported by others, there will be
significant implications regarding mood and possibly the treatment of mood
disorders. The latter possibility is strengthened by the isolated reports of
successful treatment of depressive illness by calcium channel blockers (Dubovsky
et al., 1982; Caillard et al., 1982) and the recent finding of the effectiveness
of supplemental dietary calcium in treatment Of the affective symptoms of the
menstrual cycle (Alvir & Thys-Jacobs, 199 1; Penland & Johnson, in
press).