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- Milk Thistle (Silybum marianum)
- Silymarin
- β-thalassemia Major
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Date:
11-15-2013 | HC# 061363-484
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Re: Silymarin Modulates Immune Markers in Patients with β-thalassemia Major
Gharagozloo
M, Karimi M, Amirghofran Z. Immunomodulatory effects of silymarin in patients
with β-thalassemia major. Int
Immunopharmacol. June 2013;16(2):243-247.
The
genetic disease known as β-thalassemia is characterized by abnormal hemoglobin,
leading to increased red blood cell (RBC) turnover and severe anemia. Blood
transfusion is a common treatment; however, lysis (breaking down) of RBCs along
with transfusions often result in excess iron, oxidative stress, and subsequent
immune problems. Milk thistle (Silybum
marianum) contains a combination of structurally related flavonolignans
(silybin A, silybin B, isosilybin A, isosilybin B, silychristin,
isosilychristin, and silydianin), which are found in an extract of the seeds
that is known as silymarin. Silymarin has shown anti-inflammatory, antioxidant,
and iron-chelating bioactivity in previous studies, and has also been reported
to modulate the immune system. This observational study investigates the
potential effects of silymarin on those with β-thalassemia major.
Included
patients had β-thalassemia and received blood transfusions, and 25 took the
pharmaceutical iron chelator desferrioxamine, while 5 did not. Those under 12
years, with hepatitis B, C, or HIV, kidney or heart problems, were pregnant,
taking additional chelators, or had trouble with oral absorption were excluded.
Patients were given Legalon® (Rottapharm|Madaus; Monza, Italy) for
12 weeks. Legalon consists of milk thistle standardized to 80% silymarin.
Patients were assigned to either a combination therapy group (desferrioxamine
at 40 mg/kg/day along with 140 mg of Legalon 3 times daily) or a silymarin-only
group (140 mg of Legalon 3 times daily). Patients kept track of their dosages,
and these "diaries," as well as pill count, served to assess
compliance. At baseline and endpoint, cell counts and immunology markers were
assessed, and function variations in immune cells plus serum levels of markers were
compared.
This
study placed most patients with β-thalassemia (n=25; mean age of 20.0 ± 5.3
years old) into the combination group. Average desferrioxamine dose was 40.0 ±
2.1 mg/kg/day 5 to 7 days per week. Those in the silymarin group (n=5) had not
taken desferrioxamine for the prior 6 months. The compliance in both groups was
rated as "excellent," and no dropouts were reported. Platelets and
RBCs, hemoglobin, hematocrit (HCT), and mean (average) hemoglobin per red blood
cell (MCH), red blood cell volume (MCV), and concentration of hemoglobin per
red blood cell (MCHC) measurements were not different between groups at
baseline.
Immune
cell percentages, including lymphocytes, natural killer (NK) cells, and CD3, 4,
and 8 co-receptors, were unchanged in both groups as compared to baseline. In
addition, immunoglobulins were not different at the end of the study in either
group. In both groups, tumor necrosis factor-α (TNFα) concentrations were
significantly less as compared to baseline values (P<0.05), and neopterin
was significantly elevated in both groups as compared to baseline (P<0.05).
Also, both interleukin-4 (IL-4) and interferon-γ (IFNγ) cytokines from
peripheral blood mononuclear cells stimulated in vitro with phytohemagglutinin significantly
increased in both groups at the end of the study (P<0.05).
Evidence
in this study suggests that silymarin supports aspects of the immune system in
patients with β-thalassemia. Specifically, it is surmised that the stimulation
of neopterin, a marker of cellular immune system activation, may help explain
the benefits of silymarin in protecting the liver. Also, it is mentioned that
silymarin may be an immunostimulant at low doses or an immunosuppressant at
high doses, an important factor to consider in comparing studies, as silymarin
in most formulations is not readily absorbed in the intestine. Despite positive
results, and even though baseline levels allowed each patient in the
combination therapy group to serve as their own control to compare with effects
of desferrioxamine alone, the inclusion of a desferrioxamine arm by itself in
this study would have further clarified silymarin's efficacy as an immune
support. In summary, this study shows that silymarin may have potential in
supporting the immune system of those suffering from iron excess, such as in patients
with β-thalassemia.
—Amy C. Keller,
PhD
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