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Monday 10 July 2023

Milk Thistle - Silymarin and Silychristin

We need to be careful regarding Milk Thistle. There have been many claims for Milk Thistle over the years. Often suggested for people with liver-related issues.
 
But the only person I know who tried it felt unwell from taking it. So I have long been cautious.

This is a long and detailed page by Tania S. Smith, PhD,on the excellent Thyroid Patients Canada site which explains the issues and specific circumstances in which it should be avoided.

If you are considering taking Milk Thistle it really is worth some time reading this first.

Milk thistle alters thyroid hormone transport
January 16, 2022

https://thyroidpatients.ca/2022/01/16/milk-thistle-thyroid-transport/
 
This paper identifies a potentially significant issue with a constituent of Milk Thistle.
 
Endocrinology . 2016 Apr;157(4):1694-701.
 doi: 10.1210/en.2015-1933. Epub 2016 Feb 24.

Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8

Jörg Johannes 1 , Roopa Jayarama-Naidu 1 , Franziska Meyer 1 , Eva Katrin Wirth 1 , Ulrich Schweizer 1 , Lutz Schomburg 1 , Josef Köhrle 1 , Kostja Renko 1
Affiliations
•    PMID: 26910310
•    DOI: 10.1210/en.2015-1933
Abstract
Thyroid hormones (THs) are charged and iodinated amino acid derivatives that need to pass the cell membrane facilitated by thyroid hormone transmembrane transporters (THTT) to exert their biological function. The importance of functional THTT is affirmed by the devastating effects of mutations in the human monocarboxylate transporter (MCT) 8, leading to a severe form of psychomotor retardation. Modulation of THTT function by pharmacological or environmental compounds might disturb TH action on a tissue-specific level. Therefore, it is important to identify compounds with relevant environmental exposure and THTT-modulating activity. Based on a nonradioactive TH uptake assay, we performed a screening of 13 chemicals, suspicious for TH receptor interaction, to test their potential effects on THTT in MCT8-overexpressing MDCK1-cells. We identified silymarin, an extract of the milk thistle, to be a potent inhibitor of T3 uptake by MCT8. Because silymarin is a complex mixture of flavonolignan substances, we further tested its individual components and identified silychristin as the most effective one with an IC50 of approximately 100 nM. The measured IC50 value is at least 1 order of magnitude below those of other known THTT inhibitors. This finding was confirmed by T3 uptake in primary murine astrocytes expressing endogenous Mct8 but not in MCT10-overexpressing MDCK1-cells, indicating a remarkable specificity of the inhibitor toward MCT8. Because silymarin is a frequently used adjuvant therapeutic for hepatitis C infection and chronic liver disease, our observations raise questions regarding its safety with respect to unwanted effects on the TH axis.

 
Full paper accessible here:
 
https://academic.oup.com/endo/article/157/4/1694/2422745?login=false

There has long been the received wisdom that T3 does not cross the placenta. I am not aware this has been proved in any level of detail.
 
This paper appears to make that look wrong.
 
Indeed, it appears to identify specific pharmaceutical agents which directly and significantly affect T3 transport.
 
Silychristin is a constituent of Milk Thistle extract and its impact suggests that it should be avoided in pregnancy - and possibly other circumstances.
 
 ThyroidVol. 32, No. 9 Thyroid Economy: Regulation, Cell Biology, and Thyroid Hormone Metabolism and ActionOpen AccessCreative Commons license

Thyroid Hormone Transporters in a Human Placental Cell Model

Zhongli Chen,
A.S. Elise van der Sman,
Stefan Groeneweg,
Linda Johanna de Rooij,
W. Edward Visser,
Robin P. Peeters, and
Marcel E. Meima
Published Online:14 Sep 2022 https://doi.org/10.1089/thy.2021.0503
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Abstract

Background: Fetal brain development in the first half of pregnancy is dependent on maternal thyroid hormone (TH), highlighting the importance of trans-placental TH transport. It is yet unclear which transporters are involved in this process. We aimed to identify the major TH transporters in a human placental cell model (BeWo cells).


Methods: Messenger RNA expression of the known TH transporters (the monocarboxylate transporter [MCT]8, MCT10, the L-type amino acid transporter [LAT]1, LAT2, the organic anion transporting peptide [OATP]1A2 and OATP4A1) in BeWo cells and human placenta were determined by quantitative PCR. To determine the specificity and efficacy of transporter inhibitors, we first determined TH uptake at different inhibitor concentrations in African green monkey kidney fibroblast-like cells (COS1 cells) overexpressing TH transporters. We then tested TH uptake in BeWo cells in the presence or absence of the optimal inhibitor concentrations.


Results: All tested TH transporters were expressed in human term placentas, whereas MCT8 was absent in BeWo cells. Both 2-amino-2-norbornanecarboxylic acid (BCH) and L-tryptophan at 1 mM inhibited LATs, whereas at the highest concentration (10 mM) L-tryptophan also inhibited MCT10. Verapamil inhibited OATP1A2 and less efficiently both MCTs, but not LATs. Both rifampicin and naringin reduced OATP1A2 activity. Finally, silychristin inhibited MCT8 at submicromolar concentrations and OATP1A2 partially only at the highest concentration tested (10 μM). In BeWo cells, verapamil reduced triiodothyronine (T3) uptake by 24%, BCH by 31%, and 1 mM L-tryptophan by 41%. The combination of BCH and verapamil additively decreased T3 uptake by 53% and the combination of BCH and 10 mM L-tryptophan by 60%, suggesting a major role for MCT10 and LATs in placental T3 uptake. Indeed, transfection of BeWo cells with MCT10-specific small interfering RNA significantly reduced T3 uptake. Only the combination of BCH and verapamil significantly reduced thyroxine (T4) uptake in BeWo cells, by 32%.


Conclusions: Using pharmacological inhibitors, we show that MCT10 and LATs play a major role in T3 uptake in BeWo cells. T4 uptake appears independent of known TH transporters, suggesting the presence of, currently unknown, alternative transporter(s).

 
Full paper accessible here:
 
https://www.liebertpub.com/doi/10.1089/thy.2021.0503

And this is a search for other Thyroid UK (HealthUnlocked) posts about Milk Thistle.

https://healthunlocked.com/thyroiduk/search/posts?query=milk%20thistle&page=1

 

If you find anything incorrect, misleading, typos, links that don’t work, etc., please let me know. Go to my profile and use the contact details there:

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