Milk Thistle – Silymarin

Index
Possible benefits
Mechanism of Action
Side Effects
Dosage
Calculate How Much Silymarin

Possible Benefits

To Follow

Mechanism of Action

Silymarin can control the production of Aβ by inhibiting the precursor substance of Aβ (β-amyloid precursor protein), and it can inhibit the polymerization of Aβ.

Silymarin can also increase the acetylcholine content in the nervous system by inhibiting cholinesterase activity. At the same time, it also has the effect of resisting oxidative stress and the inflammatory response of the nervous system.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539875/

Scientists hypothesize that silymarin might act on the biological pathways to:

• Increase liver regeneration by enhancing the production of DNA and RNA
• Prevent poisoning from drugs and toxic substances by making the membrane of liver cells less penetrable to them
• Affect the division of liver viruses such as Hepatitis C
• Neutralize free radicals and increase levels of the antioxidant glutathione
• Reduce inflammatory cytokines (TNF-a, INF-b) and raise anti-inflammatory defense (IL-10)

Source https://supplements.selfdecode.com/blog/milk-thistle-dosage-side-effects/

Side Effects

• Nausea, stomach pain, and discomfort (most common)
• Diarrhea
• Headaches
• Joint pain
• Skin allergies, itching, and eczema
• Fatigue and insomnia
• Nasal congestion, runny nose, sneezing
• Impotence (rare)
• Anaphylaxis (serious life-threatening allergic reaction) (very rare)
• Intestinal gas
• Fullness or pain in the stomach
• Loss of appetite
• Back pain
• Dizziness
• Hair loss

Source https://supplements.selfdecode.com/blog/milk-thistle-dosage-side-effects/ & https://www.medicoverhospitals.in/medicine/silymarin

Contraidincations

https://www.webmd.com/vitamins/ai/ingredientmono-138/milk-thistle

MODERATE interaction with Milk Thistle

• medications changed by the liver include acetaminophen (Tylenol, others) and oxazepam (Serax), haloperidol (Haldol), lamotrigine (Lamictal), morphine (MS Contin, Roxanol), zidovudine (AZT, Retrovir)
• might increase how much tamoxifen is absorbed by the body
• Milk thistle can lower blood sugar levels. 
• The dose of your diabetes medication might need to be changed. Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, metformin (Glucophage), pioglitazone (Actos), rosiglitazone (Avandia)
• might decrease how well the liver breaks down sirolimus (Rapamune)
• might decrease how well the body breaks down raloxifene in the intestines
• Some medications are moved by pumps in cells. Milk thistle might make these pumps less active and increase how much of some medications get absorbed by the body. This might cause more side effects from some medications. Some medications that are moved by these pumps include etoposide, paclitaxel, vinblastine, vincristine, vindesine, ketoconazole, itraconazole, amprenavir, indinavir, nelfinavir, saquinavir, cimetidine, ranitidine, diltiazem, verapamil, digoxin, corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others
• might affect levels of morphine in the blood
• might decrease how quickly the body breaks down ledipasvir

MINOR interation

• might increase how fast the body breaks down estrogen pills to get rid of them. Also has it’s own estrogenic effect – Milk thistle extracts might act like estrogen. If you have any condition that might be made worse by exposure to estrogen, don’t use these extracts.
• might increase the effects and side effects of medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates) eg. amitriptyline (Elavil), diazepam (Valium), zileuton (Zyflo), celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), warfarin (Coumadin)
• might decrease how well medications used for lowering cholesterol eg. atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), and rosuvastatin (Crestor).
• might increase or decrease the effects of medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) eg. lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), alprazolam (Xanax), amlodipine (Norvasc), clarithromycin (Biaxin), cyclosporine (Sandimmune), erythromycin, verapamil (Calan, Isoptin)

Dosage

Dosing on the internet talks about milk thistle, milk thistle extract and silymarin. As silymarin is the main therapeutic I’ve looked for dosage based on the dose of Silymarin used and bought milk thistle which states the amount of silymarin contained.

Silymarin is safe in humans at therapeutic doses and is well tolerated even at a high dose of 700 mg three times a day for 24 weeks.

https://pubmed.ncbi.nlm.nih.gov/31069872/

140 mg silymarin taken orally three times per day
https://www.rxlist.com/milk_thistle/generic-drug.htm

A general, reoccurring dosage for milk thistle is 140 mg three times per day for adults. A review of the literature shows dosages for children are similar to that of adults.
https://www.liversupport.com/milk-thistle-dosage

Liver

an extract containing 200 to 400 mg/day of silymarin is considered effective in various liver disorders. https://www.medicoverhospitals.in/medicine/silymarin

Non-Alcoholic Fatty Liver Disease: In a study done on patients given approximately 400 mg/day of silymarin in a phosphatidylcholine base, it was found that plasma liver enzymes fell, indices of liver fibrosis decreased, and there was a persistent reduction in liver steatosis (fat in liver)
https://www.liversupport.com/milk-thistle-dosage

Non-Alcoholic Steatohepatitis (NASH): An animal study compared a placebo group with a group given 200 mg/kg body weight silymarin for 12 weeks to two groups of rats with NASH. The placebo group went on to develop all the indices of advanced NASH while the treatment group showed improved steatosis, decreased inflammation, improved insulin response, and decreased lipid peroxidation
https://www.liversupport.com/milk-thistle-dosage

Diabetes

Diabetes and Insulin Resistance: Clinical data has shown that 140 mg 3x daily for 45 days statistically reduced fasting glucose by 11% and HBA1C (Hemoglobin A1C) by 14% and improved insulin resistance as compared to baseline. Taking a higher amount, 200 mg/day for four months reduced fasting glucose by 23-43 mg/dl and HBA1C by 1% to 1.5% compared to baseline
https://www.liversupport.com/milk-thistle-dosage

Silymarin 200 mg three times a day in combination with conventional treatment
https://reference.medscape.com/drug/carduus-marianum-holy-thistle-milk-thistle-344521v

Calculate How Much Silymarin

Milk Thistle dosage is hard to understand and compare across products because the dose advertised is the amount of milk thistle and the strength of the silymarin (usually you are aiming for 80% strength). But this doesn’t represent the amount of silymarin used in research studies.

Some products will say on the nutrition information/ingredients how much silymarin is in each capsule or tablet. That’s straightforward.

If not look to see how much “Milk Thistle Extract” it contains. This is the number you want to find 80% of (or whatever strength is listed) for the amount of silymarin.

For example here are some products compared. You can see the mg of milk thistle on the front of the label doesn’t relate directly to the Silymarin dosage.

Milk Thistle mg on Front Label	Concentration of Extract on label	Milk Thistle Extract (milk thistle divided by concentration)	Strength of Silymarin on label %	Silymarin mg (strength % of milk thistle extract)
4000mg	40:1	(4000/40) = 100mg	80%	(100/80)*100 = 80mg
5000mg	40:1	(5000/40) = 125mg	80%	(125/80)*100 = 100mg
2000mg	20:1	(2000/20) = 100mg	80%	(100/80)*80 = 80mg
3500mg	60:1	(3500/60) = 58.33mg	80%	(58.33/80)*100 = 46.67mg

You may need to calculate the Milk Thistle Extract mg if this isn’t listed and you can only do that if the concentration ration is stated somewhere on the label.

To calculate the silymarin mg in a product where it is not stated, follow this example:

1. Serving size here is 3 tablets/3000mg but we’ll calculate for one tablet
2. If it states the Milk Thistle Extract in mg go to Step 5. Otherwise calculate the Milk Thistle Extract mg.
3. Divide the Milk Thistle content on the front (1000mg) by the concentration on the back (10:1)
4. 1000mg/10 = 100mg Milk Thistle Extract
5. Find the Silymarin strength (80%)
6. Apply that percentage to the Milk Thistle Extract we just calculated
7. (100mg/80)*100 = 80mg Silymarin