High Dose Vitamin E Supplements Antagonize Vitamin K


May 7, 2013
These studies indicate that overdosing on Vitamin E antagonizes Vitamin K by reducing its tissue levels. The reduction appears to be partly related to the phenomenon thatg Vitamin E and K share similar transporters/metabolizing enzymes. When high dose Vitamin E is given it may block the transporters/enzymes that are needed to integrate Vitamin K into the appropriate tissues.

So similar to Aspirin, one should consider supplementing Vitamin K when trying high dose Vitamin E. Otherwise he may risk Vitamin K deficiency which can cause downstream problems. This effects also appears to affect natural and not only synthetic vitamin E as seen in the study by Booth et al who used natural RRR alpha-tocopherol (fourth reference).

Randomized controlled trials on Vitamin E indicate that this effect may affect overall mortality. In these trials only lower-dose Vitamin E supplementation (<400IE/day) had beneficial effects on mortality, while no beneficial effect and partly deleterious effects were found for high dose Vitamin E supplements (>400IE/day). There are no trials that studied a combination of Vitamin E with Vitamin K.

Some people mentioned side effects when trying high dose Vitamin E. I wonder whether those side effects are also related to its direct Vitamin K antagonizing effect.


Coagulopathy Associated With Vitamin E Ingestion

Thirteen-week toxicity study of d-alpha-tocopheryl acetate (vitamin E) in Fischer 344 rats.

Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet

Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status.


Supplementation of rats with a lutein mixture preserved with vitamin E reduces tissue phylloquinone and menaquinone-4.

Haemorrhagic toxicity of a large dose of alpha-, beta-, gamma- and delta-tocopherols, ubiquinone, beta-carotene, retinol acetate and L-ascorbic acid in the rat.

Interaction of vitamins E and K: effect of high dietary vitamin E on phylloquinone activity in chicks.

Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone.



May 24, 2013
Thanks a lot, I'd kind of heard of that, but had not given it enough importance.

I'll definitely look into starting up K supplementation again. Of course, I get some issues with that too, but hopefully it'll all balance out ;)


New Member
Dec 12, 2014
Hi Yall,

Thank you for the articles! Very interesting reading. Maybe the shared enzymes, I believe to cleave the side-chain(?) would account for why the few people I have read who tried taking higher doses of MK-7 had adverse reactions, whereas high doses of MK-4 seem relatively benign.

I am currently taking 42 mg of MK4 per day, and I also wonder if high doses of MK-4 would deplete or interfere with vitamin E? For the record, I am guessing it does not, or if it does, the effects would be minimal...but it is just a guess. Does anyone have any insight?


Mar 29, 2014
Welcome aaron-c :welcome


Nov 11, 2014
I'm taking 400 IU of vitamin E, but notice that my K levels are quite low. Maybe this should be done intermittently in light of this news.


Jun 7, 2013
@haidut So is there a ratio we should be shooting for? Haiduts estroban is 100iu of E for every 2 mg k2...so if you were taking 400iu of E would 8mg K2 balance appropriately or am I missing something?


Oct 30, 2015
I just found this study Excess α-tocopherol decreases extrahepatic phylloquinone in phylloquinone-fed rats but not menaquinone-4 in menaquinone-4-fed rats. - PubMed - NCBI

In this study, it appears that alpha-tocopherol didn't affect MK4 levels when rats were supplemented with MK4.
α-tocopherol did however lower phylloquinone (K1) levels, as seen in the OP studies.

After PK administration, α-tocopherol was observed to decrease PK in kidney, adrenal gland, lung, testis, and brain but not in serum and liver, whereas, after MK-4 administration, α-tocopherol did not affect MK-4 in serum and tissues.

Could it be that α-tocopherol mainly lowers K1, thus depleting substrate for K2 production, leading to the observed lower K1 and K2 levels, when rats are fed only K1?

Maybe vitamin E then isn't such a big threat to vitamin K status for those of us supplementing K2, which i guess would be most of us here.

Also, interesting snippet about gamma-tocopherol not lowering extrahepatic K1 like alpha-tocopherol;
Initially, the dietary effect of RRR-α-tocopherol, but not RRR-γ-tocopherol, in decreasing extrahepatic PK concentrations was confirmed.


Jul 13, 2017
Sun Coast, USA
Damn man, how is one supposed to properly balance this all out ? I take D and K separately from E and A, separate days too.
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