International Journal of Sport Nutrition and Exercise Metabolism, 2007, 17, 378-390
© 2007 Human Kinetics, Inc.
The Effect of 4 Wk of Oral Echinacea
Supplementation on Serum Erythropoietin
and Indices of Erythropoietic Status
Malcolm T. Whitehead, Tyler D. Martin, Timothy P. Scheett,
and Michael J. Webster
The purpose of this investigation was to determine whether echinacea supplementation results in alterations of erythroid growth factors and erythropoietic status.
Twenty-four men age 24.9 ± 4.2 y, height 1.7 ± 0.8 m, weight 87.9 ± 14.6 kg,
and 19.3% ± 6.5% body fat were grouped using a double-blind design and selfadministered an 8000-mg/d dose of either echinacea (ECH) or placebo (PLA) in 5
× 400 mg × 4 times/d for 28 d. Blood samples were collected and analyzed for red
blood cells (RBCs), hematocrit (Hct), hemoglobin (Hb), mean corpuscular volume,
mean corpuscular hemoglobin content, prostaglandin E2, ferritin, erythropoietin
(EPO), interleukin 3 (IL-3), and granulocyte-macrophage-colony-stimulating
factor using automated flow cytometry and ELISA. ANOVA was used to determine
significant differences (P ≤ 0.05). EPO was greater (P < 0.001) in ECH at Days
7, 14, and 21 and reflected a 44%, 63%, and 36% increase, respectively. IL-3 was
greater (P = 0.011) in ECH at Days 14 and 21, which indicated a 65% and 73%
increase, respectively. These data indicate that ECH supplementation resulted in
an increase in EPO and IL-3 but did not significantly alter RBCs, Hb, or Hct.
Key Words: erythropoiesis, red blood cells, IL-3, erythroid growth factors, nutrition, exercise physiology
Echinacea is an herbal supplement that is derived from the North American
purple coneflower plant and is traditionally considered a nonspecific immunostimulant. Evidence from animal models (15, 26) and cell cultures (6, 25, 33) indicates
that echinacea supplementation might also stimulate the production of erythroid
growth factors, induce erythropoiesis, and increase the oxygen-transport capacity
of the blood. Echinacea supplementation in humans (3200 g/d for 30 d) resulted
in a 5% “nonsignificant” increase in maximal oxygen consumption (VO2max) in
untrained subjects (35). Another investigation reported that echinacea supplementation (1000 mg/d for 42 d) resulted in an increase in the number and size of red blood
cells (RBCs), hemoglobin (Hb), and hematocrit (HCT) in an animal model (26).
Whitehead is with the Dept. of Health and Human Performance, Northwestern State University,
Natchitoches, LA 71497. Martin and Webster are with the Dept. of Human Performance and Recreation,
University of Southern Mississippi, Hattiesburg, MS 39406-0001. Scheett is with the Dept. of Physical
Education and Health, College of Charleston, Charleston, SC 29464.
378
Echinacea and Erythropoietic Status 379
One explanation to account for the echinacea-induced erythrocythemia and
increased VO2max is an increase in serum erythropoietin (EPO) and other erythropoietic growth factors.
RBCs develop from stem cells after stimulation by several growth factors including EPO, interleukin-3 (IL-3), and granulocyte-macrophage-colonystimulating factor (GM-CSF). EPO, a hormone that is secreted from the kidney,
is considered a primary stimulator of erythropoiesis that acts by promoting the
formation and release of RBCs from the bone marrow (19). Ferritin is widely used
as a marker of iron storage (23), and subjects treated with EPO exhibit a rapid
decrease in ferritin to levels 50–75% below baseline (16, 32). RBC production is
thought to be regulated within narrow limits so that an adequate number of RBCs
is maintained to provide sufficient tissue oxygenation while simultaneously not
promoting excessive hemoconcentration, which can impede blood flow (17). The
accepted mechanism for the regulation of EPO production dictates that any condition that results in a decrease in the quantity of oxygen transported in the blood to
the tissues, specifically the peritubular capillaries of the kidneys, will result in an
increase in circulating EPO and subsequent RBC production (17). This view was
founded on observations made in a variety of clinical disorders; the control of EPO
production in healthy individuals might not be quite the same (7).
Research indicates that another protein, prostaglandin E2 (PGE2), appears to
stimulate production of EPO (5, 18, 20, 27). Echinacea has been shown to stimulate
macrophage activity, and an increase in macrophage activity can result in an increase
in PGE2 secretion from active macrophages (6, 15, 25, 29, 30, 33). In addition, an
increased concentration of PGE2 has been shown to stimulate GM-CSF release
from cultured smooth-muscle cells, which is also an erythroid progenitor growth
factor (21). Furthermore, echinacea has been shown to increase the activity level
of T-cells in vitro, and activated T-cells are known to synthesize GM-CSF and the
erythroid progenitor growth factor IL-3 (4, 9, 10, 14, 25, 28). These results suggest that echinacea might enhance EPO production and that the mechanism might
be mediated through an increase in the circulating concentrations of PGE2, IL-3,
and GM-CSF.
To date, no studies have been performed with human subjects that have evaluated the effects of oral echinacea supplementation on the serum concentrations of
erythroid growth factors and markers of erythropoietic status. Thus, the present study
was designed to investigate the effects of 28 d of oral echinacea supplementation
on RBC count, Hb, HCT, mean corpuscular volume (MCV), and mean corpuscular
hemoglobin content (MCHC) and to determine whether these measures of erythropoietic status are affected by alterations in serum ferritin, EPO, PGE2, IL-3, or
GM-CSF of human subjects.
Methods
Participants
Twenty-four apparently healthy, recreationally active male students between the
ages of 18 and 30 y were recruited to participate in this investigation. Participant
characteristics are presented in Table 1. All volunteers were verified as being recreationally active (i.e., ≥30 min 3 d/wk) by a physical activity questionnaire, not
380 Whitehead et al.
Table 1 Descriptive Characteristics of Participants
Group
Placebo (n = 12)
Echinacea (n = 12)
Age (y)
24.9 ± 3.6
25.2 ± 1.4
Height (cm)
180.3 ± 2.0
177.5 ± 2.0
Weight (kg)
93.5 ± 14.7
82.4 ± 12.7
Body fat (%)
19.8 ± 7.4
18.7 ± 5.7
Values are means ± standard error of measurement; N = 24.
currently taking any medications or dietary supplements, not currently using tobacco
in any form, and free from signs, symptoms, or known cardiovascular or metabolic
diseases. The Human Subjects Protection Review Committee at the University of
Southern Mississippi approved all procedures.
Each participant provided written informed consent, and a brief medical history
was taken and evaluated before data collection. Participants were asked to abstain
from physical activity, alcohol, and caffeine for 48 h before all testing sessions.
They were asked not to make any deviations from their normal diet and exercise
patterns. Exercise and diet were monitored throughout the duration of the investigation with diet- and exercise-recall journals. Seven days before the experimental trial,
participants reported to the laboratory to undergo preliminary testing that included
a blood sample and measurement of height, weight, and body composition. Height
was measured with a stadiometer, and weight was measured with an electronic
balance. Body composition was measured with dual-energy X-ray absorptiometry
(Prodigy Lunar, GE Medical Systems, Madison, WI).
Study Design
Participants were placed in either the echinacea (ECH) or placebo (PLA) experimental group in a randomized-match and double-blind design and supplemented
for 28 consecutive days. The first 12 participants in each group were randomly
assigned, and Participants 13–24 were grouped in a balanced manner based on RBC
count by an individual not involved in data collection for this project. Participants
self-administered either 8000 mg/d of echinacea (Echinacea purpurea, Puritan’s
Pride, Oakdale, NY) or placebo (wheat flour), and both groups supplemented with
a multivitamin for 28 consecutive days. Each participant took orally five 400-mg
capsules on 4 separate occasions during the course of each day according to the
following schedule: 1.) immediately after waking, 2.) with lunch, 3.) midafternoon,
and 4.) with the evening meal. This dose and regimen is similar to protocols used
in previous research (2, 35). Multivitamins were taken immediately after waking.
Each participant was provided with a known quantity of either ECH or PLA and
a daily log in which to document the time and dose for each self-administration
on a weekly basis. Both the daily log and any unused capsules were returned to
the investigators so they could document adherence to the dosage protocol on a
weekly basis.
Blood Collection
Baseline blood samples were collected on Day 0 for comparison with subsequent
samples taken on Days 7, 14, 21, and 28 during the supplementation period. Wholeblood samples were collected and analyzed for RBC count, Hb, HCT, MCV, and
Echinacea and Erythropoietic Status 381
MCHC. Serum samples were collected, processed, and stored for analyses of ferritin,
EPO, PGE2, IL-3, and GM-CSF. Each sample was collected between 6 and 9 AM
after a 12-h fast. Before collection of each blood sample, an indwelling cannula
(JELCO, Johnson & Johnson Medical, Arlington, TX) was placed in a superficial
forearm vein and kept patent with saline. Participants were then required to rest
in a seated position for 30 min to allow for stabilization of body fluids. The first 3
mL of each sample were discarded, and then 15 mL were collected, with 5 and 10
mL separated into EDTA and serum tubes, respectively.
Sample Analyses
Whole-blood samples were analyzed for RBC count, Hb, HCT, MCV, and MCHC
(Gen∙S System 2 Hematology Workstation, Beckman Coulter, Fullerton, CA).
Serum samples were allowed to clot for 20 min at room temperature and then
centrifuged for 10 min at 5000 rpm and 4 °C. The separated samples were then
decanted into 2.5-mL polyethylene storage tubes and frozen at –80 °C until completion of data collection.
Serum samples were analyzed in duplicate for ferritin, EPO, IL-3, PGE2,
and GM-CSF using ELISA and analyzed on a VersaMax microplate reader and
accompanying software (SoftMax Pro v. 4.3, Molecular Devices, Sunnyvale, CA).
Each participant’s duplicate samples were analyzed from the same ELISA kit.
Sensitivities and intra-assay coefficients of variation for ferritin (5.0 ng/mL and
3.24%, respectively, BC-1025, ALPCO Diagnostics, Windham, NH), EPO (0.6
mU/mL and 2.78%, respectively, DEP00, R&D Systems, Minneapolis, MN), IL-3
(7.4 pg/mL and 9.51%, respectively, D3000, R&D Systems), PGE2 (8.25 pg/mL
and 2.33%, respectively, DE1200, R&D Systems), and GM-CSF (0.26 pg/mL and
5.76%, respectively, HSGM0, R&D Systems) were determined by following the
respective manufacturers’ directions.
Statistical Analysis
Repeated-measures analysis of variance (ANOVA) was performed to determine
significant main effects between the groups and across time for RBC count, Hb,
HCT, MCV, MCHC, ferritin, EPO, PGE2, IL-3, and GM-CSF. Post hoc analyses were
performed for all variables that exhibited significant main effects using independentsample t-tests. A 1-way ANOVA was performed to determine differences across
time within each group that exhibited significant main effects and was followed
with Bonferroni-adjusted multiple comparisons. Effect size was calculated using
Cohen’s d or eta2 (η2). Significance for all analyses was set at P ≤ 0.05.
Results
Results for analyses of erythropoietic status from whole-blood samples are presented
in Table 2. All data are presented as mean ± standard error. Mean replacement was
used to extrapolate data for a single time point for RBC count, Hb, HCT, MCV, and
MCHC because of loss of viability of 1 sample. There were no significant main
effects detected between the groups for RBC count, Hb, HCT, MCV, or MCHC.
Results of analyses of erythropoietic growth factors from serum samples are reported
382 Whitehead et al.
Table 2 Effect of 4 Wk of Oral Echinacea Supplementation (8000 mg/
d) on Measures of Erythropoietic Status
Variable
RBC (× 1012/L)
placebo
echinacea
Hb (g/dL)
placebo
echinacea
HCT (%)
placebo
echinacea
MCV (µm3)
placebo
echinacea
MCHC (g/dL)
placebo
echinacea
Pretrial
Day 7
Time
Day 14
Day 21
Day 28
4.78 ± 0.04
4.70 ± 0.07
4.69 ± 0.03
4.71 ± 0.12
4.71 ± 0.04
4.72 ± 0.10
4.77 ± 0.06
4.71 ± 0.08
4.73 ± 0.07
4.78 ± 0.10
14.7 ± 0.1
14.5 ± 0.2
14.5 ± 0.1
14.3 ± 0.23
14.5 ± 0.1
14.4 ± 0.2
14.7 ± 0.1
14.4 ± 0.2
14.5 ± 0.2
14.6 ± 0.2
42.5 ± 0.3
41.9 ± 0.5
41.8 ± 0.5
41.7 ± 0.5
42.0 ± 0.4
42.1 ± 0.4
42.7 ± 0.5
42.1 ± 0.4
42.3 ± 0.5
42.9 ± 0.5
88.3 ± 1.3
89.1 ± 1.1
88.4 ± 1.4
89.1 ± 1.2
88.3 ± 1.3
89.5 ± 1.3
88.8 ± 1.2
89.5 ± 0.9
88.5 ± 1.3
90.4 ± 1.1
34.6 ± 0.1
34.2 ± 0.2
34.5 ± 0.2
34.3 ± 0.2
34.5 ± 0.2
34.1 ± 0.2
34.3 ± 0.2
33.9 ± 0.2
34.2 ± 0.1
33.9 ± 0.2
Values are mean ± standard error; n = 24. RBC indicates red blood cells; Hb, hemoglobin; Hct, hematocrit; MCV, mean corpuscular volume; MCHC, mean corpuscular hemoglobin content.
in Table 3. There were no significant main effects detected between the groups for
ferritin, PGE2, or GM-CSF. Significant between-subject effects were noted for EPO,
F(1, 22) = 35.162, P < 0.001, η2 = 0.615, and IL-3, F(1, 22) = 7.617, P = 0.011,
η2 = 0.257. Repeated-measures ANOVA was followed with independent-sample ttests for preintervention and Days 7, 14, 21, and 28. Results of independent-sample
t-tests indicated that the ECH group had significantly greater serum EPO than the
PLA group at Day 7, t(22) = –4.605, P < 0.001, d = 1.96; Day 14, t(22) = –5.733,
P < 0.001, d = 2.44; and Day 21, t(22) = –3.529, P = 0.002, d = 1.50, as depicted in
Figure 1. Erythropoietin was 44%, 63%, and 36% greater than baseline at Days 7,
14, and 21, respectively. One-way ANOVA revealed a significant difference in the
means within the ECH group with respect to EPO, F(4, 59) = 25.118, P < 0.001, d
= 2.14. Within-group multiple comparisons indicated that EPO was significantly
greater than the preintervention measure at Days 7, 14, and 21 (P = 0.007, P < 0.001,
and P = 0.003, respectively). Results of independent-sample t-tests indicated that
the ECH group had significantly greater IL-3 than the PLA group at Day 14, t(22)
= –4.538, P < 0.001, d = 1.94, and Day 21, t(22) = –3.070, P < 0.006, d = 1.31, as
depicted in Figure 2. IL-3 was 65% and 73% greater than baseline in ECH at Days
14 and 21, respectively. A 1-way ANOVA indicated a significant difference in the
means within the ECH group with respect to IL-3, F(4, 59) = 13.539, P < 0.001,
d = 1.57. Within-group multiple comparisons indicated that IL-3 was significantly
greater than the preintervention measures at Days 14 and 21 (P < 0.001).
Echinacea and Erythropoietic Status 383
Table 3 Effect of 4 Wk of Oral Echinacea Supplementation (8000 mg/
d) on the Serum Concentration of Erythropoietic Growth Factors
Variable
EPO (mU/mL)
placebo
echinacea
IL-3 (pg/mL)
placebo
echinacea
PGE2 (pg/mL)
placebo
echinacea
GM-CSF (pg/mL)
placebo
echinacea
Ferritin (ng/mL)
placebo
echinacea
Pretrial
Day 7
Time
Day 14
Day 21
Day 28
10.63 ± 0.68 10.02 ± 0.72 10.46 ± 0.91 8.64 ± 0.81 9.54 ± 0.98
12.37 ± 0.87 17.79 ± 1.52* 20.21 ± 1.43* 16.84 ± 2.17* 10.32 ± 0.51
291.6 ± 28.3 326.8 ± 20.8 347.6 ± 13.5 325.2 ± 26.6 261.7 ± 17.4
279.0 ± 27.7 325.7 ± 13.2 460.9 ± 21.0* 483.1 ± 44.1* 279.2 ± 17.8
9.22 ± 0.95 11.24 ± 2.26
10.42 ± 1.72 13.38 ± 3.07
11.50 ± 1.52
15.21 ± 4.67
10.64 ± 1.81 13.58 ± 3.92
11.74 ± 1.82 10.45 ± 1.90
0.67 ± 0.04
0.62 ± 0.04
0.75 ± 0.03
0.74 ± 0.02
0.80 ± 0.03
0.80 ± 0.04
0.80 ± 0.03
0.82 ± 0.04
0.79 ± 0.05
0.84 ± 0.03
54.1 ± 3.8
61.3 ± 5.2
49.6 ± 4.7
59.7 ± 4.8
43.8 ± 5.6
56.4 ± 9.1
45.0 ± 4.6
55.8 ± 4.5
46.5 ± 3.3
44.7 ± 3.4
Values are mean ± standard error; N = 24. EPO indicates erythropoietin; IL-3, interleukin 3; PGE2, prostaglandin E2; GM-CSF, granulocyte-macrophage-colony-stimulating factor.
*Significantly different from placebo, P ≤ 0.05.
Figure 1 — Effects of 4 wk of oral echinacea (ECH) supplementation (8000 mg/d) on
serum erythropoietin (EPO). *Significant difference between groups (P ≤ 0.05). †ECH group
significantly different within group from pretrial (P ≤ 0.05). ‡ECH group significantly different within group from Day 7 (P ≤ 0.05). £ECH group different within group from Day
14 (P ≤ 0.05). §ECH group significantly different within group from Day 21 (P ≤ 0.05).
¥ECH group significantly different within group from Day 28 (P ≤ 0.05).
384 Whitehead et al.
Figure 2 — Effects of 4 wk of oral echinacea (ECH) supplementation (8000 mg/d) on
serum interleukin 3 (IL-3). *Significant difference between groups (P ≤ 0.05). †ECH group
significantly different within group from pretrial (P ≤ 0.05). ‡ECH group significantly different within group from Day 7 (P ≤ 0.05). £ECH group significantly different within group
from Day 14 (P ≤ 0.05). §ECH group significantly different within group from Day 21 (P ≤
0.05). ¥ECH group significantly different within group from Day 28 (P ≤ 0.05).
Discussion
The major finding of the present investigation was a significant increase in serum
EPO at Days 7 (44%), 14 (63%), and 21 (36%) of the supplementation period in the
ECH group that was significantly greater than serum EPO in the PLA group. This
is the first investigation to report a significant increase in serum EPO attributable
to oral supplementation with echinacea in human or animal subjects.
The primary cells acted on by EPO in the bone marrow are the colonyforming unit erythroids (CFU-E), which is in response to the greater quantity of EPO
receptors on this cell than on other cells in the red-cell lineage (13). Erythropoietin
acts synergistically with other erythroid growth factors including GM-CSF and IL-3
to induce maturation and proliferation from the stage of burst-forming erythroid
(BFU-E) and CFU-E to the normoblast stage of erythroid cell development (13).
It is currently thought that EPO acts primarily through an apoptotic mechanism
to decrease the rate of cell death of erythroid progenitor cells in the bone marrow
(13). Other erythroid growth factors including IL-3 cause differentiation into the
myeloid stem cell and the colony-forming unit granulocyte erythroid monocyte
megakaryocyte (CFU-GEMM) (13). The CFU-GEMM then gives rise to the specific
colony-forming units that become erythroid cell precursors (13).
The increases in serum EPO reported in the current investigation are similar
to the results from previously reported research demonstrating an increase in
serum EPO after exposure to hypoxia through a “live-high, train-low” regimen
(8). The stimulus used to induce an increase in serum EPO in those “live-high,
Echinacea and Erythropoietic Status 385
train-low” investigations was 28 d spent living at a moderate altitude of 2,500 m
while training at 1250 m above sea level (8). Chapman (8) reported a significant
30% increase in serum EPO (12.5 mU/mL at baseline vs. 16.2 mU/mL after 14
d at altitude) in the responder group and (13.7 at baseline vs. 15.4 mU/mL after
14 d at altitude) in the nonresponder group that returned to baseline values after
28 d at sea level. The increases in serum EPO in the current investigation are
similar to previous results from several researchers who implemented hypoxic
protocols in both magnitude and response pattern with respect to time (1, 8, 36).
Hypoxia is considered the primary stimulus for increased serum EPO (3, 11–13).
The oxygen-dependent increase in EPO attributable to hypoxia is thought to be
mediated by tumor-suppressor protein Von Hipple-Lindau (24) and transcriptionfactor-complex hypoxia-inducible factor-1α (31). The EPO response appears to
vary with the magnitude of hypoxic exposure; specifically, higher altitude (4500
m) will typically induce a larger circulating EPO response than a moderate altitude (1900 m) (3). The typical response to chronic hypoxia is a gradual increase
in serum EPO with a peak occurring after 2–3 d of exposure and then a gradual
decline approximately 1 wk after the peak (3). The similarity of the results of the
current investigation to those previously reported with altitude-induced hypoxia
indicates that the observed response patterned a normal EPO response to hypoxic
stimulation; however, in this case the hypoxic stimulus was not present.
The second major finding of the current investigation was the significant
increase in serum IL-3 at Days 14 and 21 that returned to baseline at Day 28.
Echinacea has been shown to increase the activity of T-cells in vitro, and activated
T-cells are known to synthesize and secrete the erythroid progenitor growth factor
IL-3 (10, 14). The present investigation indirectly demonstrated an increase in
T-cell activity in vivo, as evidenced by a significant increase in serum IL-3. As
an erythroid growth factor, IL-3 acts in conjunction with other erythroid growth
factors in the maturation and proliferation process by stimulating differentiation
of cells in the red-cell lineage (13). IL-3 works in the first step of erythropoiesis
by initiating the maturation and proliferation of pluripotent stem cells to become
myeloid stem cells (13). IL-3 also stimulates the differentiation of CFU-GEMM
to the specific colony-forming units that become erythroid cell precursors (13).
It must also be noted that the actions of IL-3 precede the actions of EPO in differentiation of pluripotent stem cells (13). Another interesting finding of the current investigation was that the significant
increase in serum EPO was not accompanied with any statistically detectable
changes in measures of erythropoietic status, as seen in Figure 3. This phenomenon
has been previously reported with intermittent altitude (2650 m) exposure for 8–11
h per night for 5 nights (1). Another possible explanation for the lack of statistical
significance in measures of erythropoietic status is that the data-collection time
period might not have been sufficient to yield significant results. Conversely,
similar hypoxia-induced serum EPO values have elicited significant results in 27
d (8, 22, 34). The disagreement between these results and the results from the
current investigation suggests that the mechanism or time course for stimulating
EPO production might be affected when hypoxia is not used as a stimulus for
increased endogenous EPO production. This conclusion has merit in that with
hypoxia-induced EPO production a peak in serum EPO has been shown to occur
after 2–3 d of exposure, thereby allowing 25 d to demonstrate significant results
Figure 3 — Percentage change in measures of erythropoietic status during 4 wk of oral
echinacea supplementation. (a) RBC indicates red blood cells. (b) Hb indicates hemoglobin.
(c) Hct indicates hematocrit. (d) MCV indicates mean corpuscular volume.
386
Figure 4 — Percentage change in the serum concentration of erythropoietic growth factors
during 4 wk of oral echinacea (ECH) supplementation. (a) EPO indicates erythropoietin.
(b) PGE2 indicates prostaglandin E2. (c) IL-3 indicates interleukin 3. (d) GM-CSF indicates
granulocyte-macrophage-colony-stimulating factor. *Significant difference in percentage
change of serum EPO concentration between groups. †ECH group significantly different
within group from pretrial (P ≤ 0.05). ‡ECH group significantly different within group
from Day 7 (P ≤ 0.05). £ECH group significantly different within group from Day 14 (P
≤ 0.05). §ECH group significantly different within group from Day 21 (P ≤ 0.05). ¥ECH
group significantly different within group from Day 28 (P ≤ 0.05).
387
388 Whitehead et al.
as indicated in previously reported results (8, 22, 34). In the current investigation,
the peak appears to have occurred around Day 14 of the supplementation period,
thereby allowing only 14 d to demonstrate a statistically detectable change in
measures of erythropoietic status.
Although the exact mechanism of echinacea-induced EPO production cannot
be determined from the current investigation, there is evidence to indicate that IL-3
might play a role in this process. Our results suggest that echinacea supplementation might induce endogenous EPO production through activation of macrophages
and T-cells, which can secrete erythroid progenitor growth factors. Echinacea has
been shown to increase the activity level of T-cells in vitro, and activated T-cells
are known to synthesize GM-CSF and the erythroid progenitor growth factor IL-3
(4, 9, 10, 14, 25, 28). Although T-cell activity was not directly measured in the
current investigation, IL-3 was shown to be significantly greater than control and
preintervention values in the ECH group at Days 14 and 21. The increase from
preintervention values is equal to 40% and 42% at Days 14 and 21, respectively,
and the increase in serum IL-3 also parallels the observed increase in serum EPO.
Although not statistically significant, there was an upward trend in other erythropoietic growth factors, as seen in Figure 4. As expected, the peak in serum PGE2
preceded the increase in serum EPO; it must be noted, however, that the percentage
change was not significant. Echinacea has been shown to stimulate macrophage
activity, and an increase in macrophage activity can result in an increase in PGE2
secretion from active macrophages (6, 15, 25, 29, 30, 33). It is possible that echinacea increased PGE2 secretion from active macrophages, which might have induced
the increase in serum EPO. There was also a noticeable nonsignificant increase in
GM-CSF, which also parallels the increase in serum EPO and IL-3.
In conclusion, this investigation was the first to show a significant increase
in serum EPO and IL-3 that is attributable to 4 wk of echinacea supplementation.
This investigation was also the first to show a significant increase in endogenous
EPO in human subjects that was not attributable to exposure to hypoxia. It must
also be noted that the increase in serum EPO did not result in any significant
changes in the measured indicators of erythropoietic status (i.e., RBC, Hct, and
Hb). This distinction is important because erythropoiesis is a multifaceted cascade
of physiological events that is not limited to a significant increase is serum EPO.
There are, however, several nonsignificant trends in the data that suggest that
erythropoiesis might have been initiated. The specific mechanism responsible for
the significant increase in serum EPO and IL-3 cannot be determined from the
current investigation, but the significant increase in EPO after echinacea supplementation is very intriguing and warrants further investigation, possibly examining
more robust measures of erythropoietic parameters, including serum transferrin
receptor concentration, RBC mass, and Hb mass.
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