Evidence continues to grow that the silymarin complex of flavonolignans extracted from milk thistle can have an impact on serum ferritin and iron overload. There are three recent clinical trials of this extract in patients with the genetic disorder b-thalassaemia, mainly used in conjunction with the drug desferrioxamine.
Beta-thalassaemia is a relatively common genetic haemoglobin disorder that leads to severe chronic anaemia and requires regular blood transfusions. Over time these blood transfusions lead to iron overload and very high serum ferritin levels. When transferrin and ferritin’s iron-binding capacities are exceeded, the excess iron leads to harmful free radicals being formed causing tissue and multi-organ damage.1 Chelation therapy with the drug desferrioxamine is the standard therapy for these iron-induced complications. A key drawback, however, is about one-third of patients find it difficult to comply with the required, almost daily, subcutaneous infusions of this drug.
Serum ferritin levels dropped with silymarin
In the first double-blind trial, desferrioxamine and 420mg/day silymarin (n=49) or desferrioxamine and placebo (n=48) were given to patients for nine months.11 Serum ferritin levels decreased significantly from the beginning to the end of silymarin treatment (3028.8 ± 2002.6 versus 1972.2 ± 1250.6ng/mL); however, no significant change in serum ferritin was seen in the patients receiving the placebo (2249.0 ± 1304.2 versus 2015.6 ± 1146.8ng/mL). Patients on silymarin therapy also had a significant drop in serum levels of hepcidin and soluble transferrin receptor after the nine-month treatment period. (Hepcidin is a peptide hormone produced by the liver and involved in iron homeostasis.) A significant improvement in serum transaminases (liver function test) was also observed in the silymarin-treated group.
Measuring soluble transferrin receptor (sTfR) is a helpful way to monitor what the red blood cell production response is to various forms of therapy, in particular when changes in haemoglobin aren’t yet apparent. Increased values of sTfR are detectable in thalassaemia syndromes due to ineffective erythropoiesis (the process that produces red blood cells). The study revealed that combination therapy of silymarin and desferrioxamine significantly reduced levels of sTfR after the nine-month treatment compared with baseline values. To the best of the study authors’ knowledge, this was the first evidence to show the effect of iron chelation therapy (via silymarin and the drug) on sTfR levels in β-thalassaemia major.
Serum iron was reduced
The second trial was conducted over six months with 40 children (average age about five years) with b‑thalassaemia major and a serum ferritin level of more than 1000ng/mL.2 Patients were divided into two random subgroups (group IA and group IB). Group IA received oral desferrioxamine 20 to 40mg/kg/day (supplied in orally dispersible tablets dissolved in water or juice and administered on an empty stomach) together with oral silymarin in the form of 140mg tablets, one hour before each meal (in other words three times daily). Group IB received oral desferrioxamine 20 to 40mg/kg/day and a placebo. Group II included 20 healthy children matched in age and sex and served as a control group. Serum ferritin levels markedly decreased from baseline by around 67 per cent in group IA compared with 43 per cent for group IB (p = 0.001). However, levels were still well above those measured in the healthy control children. Serum iron was also reduced.
In the third study, the immunomodulatory effects of silymarin were investigated in an open-label 12-week clinical trial in two groups of patients. In the combined therapy group (n=25), patients continued subcutaneous desferrioxamine at a dose of 40mg/kg/day and silymarin tablets (420mg daily) were added.3 In the silymarin only group (n=5), patients who were unable or unwilling to use desferrioxamine received just silymarin. Immunological tests were assessed at the beginning and the end of the trial. Serum tumour necrosis factor (TNF-α) levels were significantly decreased in both groups. The analysis of cell culture supernatants of activated T cells showed increased production of interferon gamma (IFNγ) and interleukin (IL)-4 after silymarin treatment in both groups. The authors concluded that silymarin stimulated cell-mediated immune responses in β-thalassaemia major, possibly through a direct action on cytokine-producing mononuclear cells. The reduction in TNF-a also suggested an anti-inflammatory effect.
Research shows silymarin may be useful for iron overload disorders
Silymarin’s hepatoprotective and iron-bonding capacities suggest a role in iron overload disorders such as b-thalassaemia and haemochromatosis, and now there is a reasonable body of clinical evidence supporting its value in the former and preliminary evidence for the latter (see below). While the trial designs were not strong, the substantial ferritin reductions observed, suggest a clinically relevant effect.
In terms of hereditary haemochromatosis, one small study found that a single dose of silymarin (140mg) with food reduced subsequent iron absorption in patients with this disorder. Also, silymarin did reduce serum ferritin in chronic hepatitis C patients. Iron from damaged liver cells could contribute to the inflammatory pathology of this disorder. In a randomized, open-label, dose-finding study, the impact of silymarin (360, 720 or 1080mg/day) as the phosphatidylcholine (lecithin) complex was assessed in 37 patients with chronic hepatitis C and liver fibrosis. There was a highly significant 12 per cent decrease in mean serum ferritin from baseline to the end of treatment 12 weeks later (p = 0.0005). In all, 78 per cent of patients responded with a decrease in this factor.
Silymarin can help manage blood glucose levels
The potential clinical value of silymarin’s impact on iron overload extends well beyond the above disorders. One good example is type 2 diabetes. There is now a strong link between this common disorder and serum ferritin and tissue iron stores, and the relationship is thought to be causal.5 In fact, type 2 diabetes (T2D) has reversed with a reduction in iron status. Based on a recent meta-analysis there is a 1 per cent increased risk of T2D for every 5ng/mL ferritin increment, and 224 per cent for every 5mg/day intake of dietary haem iron.6 However, supplemental iron is not implicated.
In addition, silymarin also can help manage blood glucose levels. In two clinical trials in T2D patients, silymarin improved glycaemic control.8,9 It also improved BMI,8 hepatic transaminases,9and reduced urinary albumin in T2D patients with nephropathy.
To your better health,
Nutrition & Healing
Vol. 9, Issue 3 • March 2015
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