Any Problems With Taking Mega Doses (~150mg) Of Vitamin K

[encerent]

K2 (I use health natura True K2 orally) helps me profoundly with depression, anxiety and mental clarity in a dose dependent manner. The more I take the better I'm off it seems. I'm up to 100-150 mg /daily lately and haven't seen any downsides. Is there something to worry about long-term with mega doses of K2?

 

[johnwester130]

Yes, your bank balance.

 

[Koveras]

https://chrismasterjohnphd.com/2016/12/09/the-ultimate-vitamin-k2-resource/

Hypothetical Side Effects of High Doses

Long-term use of 45 mg per day of MK-4 has not revealed any established toxicity syndrome or risk of serious side effects. This is 225 times the dose I recommend. Nevertheless, the biochemistry of vitamin K suggests that unnecessarily high doses could rob the body of antioxidants or interfere with blood sugar regulation, insulin sensitivity, and hormonal health. The real question, though, is at what dose these potential side effects kick in. Since 45 mg per day has not shown any clear syndrome of toxicity and the dose I recommend is more than 200 times lower than this, I think we have a very large window of safety to work within. The potential for hypothetical side effects, however, should lead us to avoid supplementing with doses that are much larger than those that provide clear benefits.

There are several aspects of vitamin K’s biochemistry that suggest high doses could have adverse effects on our health:

Vitamins E and K are broken down in similar pathways (Shearer, 2008). High doses of either one elicit an increase in these catabolic pathways by activating a common receptor known as the steroid and xenobiotic receptor (SXR) or the pregnane X receptor (PXR). As a result, high doses of one will elicit the destruction of the other. Thus, high-dose vitamin K could contribute to vitamin E deficiency.

Second, a small portion of vitamin K is broken down to a compound known as menadione (Thijssen, 2006). Some of the menadione is used to synthesize MK-4, but high concentrations are toxic. We therefore conjugate a portion of the menadione to glutathione, the master antioxidant and detoxifier of the cell, and excrete the complex into our urine. High doses of vitamin K could therefore deplete glutathione. This would impair detoxification, and along with vitamin E depletion it would hurt antioxidant activity.

High doses of vitamin K can inhibit bone resorption, which is probably the mechanistic basis by which 45 mg/day reduce fracture risk (Iwamoto, 2013). While bone resorption sounds like a bad thing, we need to use it every day to help our bones remodel themselves and adapt their structures to our lifestyles, and to keep blood levels of calcium within a precisely controlled range. We also use bone resorption to release osteocalcin into the blood, where it acts on multiple tissues to improve our metabolic and hormonal health (Ferron, 2007; Oury, 2013). Ironically, one of the benefits of vitamin K2 is to support proper production of osteocalcin, but high doses of the vitamin could hypothetically prevent us from using it. That would be expected to hurt blood sugar control, insulin sensitivity, our metabolic rate, and, in males, testosterone production.

Japanese trials using 45 mg/day MK-4 to treat osteoporosis have not established any risk of severe side effects (Iwamoto, 2013). Most of them, however, had between 20 and 120 subjects per group. One very large two-year trial with over 2,000 subjects per group (Inoue, 2009) reported 23 percent more adverse drug reactions in the MK-4 group than in the control group. The report did not include any description of what those side effects were, but confirmed that there was no difference in “serious” adverse effects or deaths.

Such high doses are pharmacological in nature and not nutritional. We should look at their costs and benefits in the same way we look at other pharmaceutical drugs. In this light, high-dose MK-4 is remarkably safe and effective. We nevertheless have hints that negative side effects of some sort occur when using extended pharmacological doses and we have several biochemical rationales for why high doses would cause harm. This provides a basis for caution in using doses outside of the nutritional range.

 

[ecstatichamster]

I wouldn't take such high doses. I would stay in the lower range and wait it out for a bit. There are just too many negative possibilities over time at this high a dose.

 

[Such_Saturation]

I think @Dan Wich poured a bottle of Thorne on himself once. So if he replies, that means it's safe.

 

[Constatine]

This study used a comparatively larger dose than you are thinking of using and it increased testosterone by a huge factor: Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells . I wouldn't recommend it but you'll definitely not die... If you do use this please give a detailed report on how it aids you.

 

[Bahaa El wazzan]

@Constatine oh my goodness

All that mk4 for 5 weeks

Daaaam it

 

[Dan W]

I think @Dan Wich poured a bottle of Thorne on himself once. So if he replies, that means it's safe.

So far I've survived my panicked application of a spilled bottle of Thorne. Plus it gave me superpowers.

We also use bone resorption to release osteocalcin into the blood, where it acts on multiple tissues to improve our metabolic and hormonal health (Ferron, 2007; Oury, 2013). Ironically, one of the benefits of vitamin K2 is to support proper production of osteocalcin, but high doses of the vitamin could hypothetically prevent us from using it. That would be expected to hurt blood sugar control, insulin sensitivity, our metabolic rate, and, in males, testosterone production.

The comment mentioned here seems to suggest we can't conclude much about vitamin K / osteocalcin / blood sugar control. Or at least that's what I take from it, being too lazy to actually read through it carefully or follow up on the references.

 

[healthnatura]

In my practice, I've applied a simple principle for situations like this. (disclaimer: I don't know if this is Ray Peat practice or not, and is solely based on my opinion and experience) Start with loading does, that incrementally increase over time (minimum wait time: 6 weeks) till a state of optimization is felt, or a specific lab based benchmark is reached. In some instances, these doses can end up really high. Maintain this for 6-30 weeks, (depending on the situation) followed by incremental decreases till the lowest effective dose is reached. Time frames, wait times between increases/decreases, vary between substances, condition, and biological individuality. The important thing to remember is that loading doses and maintenance doses (if needed at all) can differ significantly. Also, lifestyle changes should be the primary foundation of care and recovery. Supplements, come from a foundation that they are meant to supplement, not replace, an appropriate diet and lifestyle. Otherwise we would call them replacements, not supplements.

In summary, loading doses if needed, possibly a large number of initial supplements and dietary changes may be needed to optimize the individual. Followed by the fewest number of supplements, and lowest possible effective doses for long term maintenance.

 

[rzero]

Looking at that brand of K2, I see that is has both MK-4 and MK-7 in the formula.

I have read multiple personal anecdotes of people being hospitalized with palpitations/arrhythmia after taking too much MK-7 for a period of time. One guy claimed to have permanent heart damage. The longer half-life of MK-7 is thought to be at least one of the reasons this happens with MK-7, and not MK-4. MK-7 can build up to dangerous levels over time, apparently.

After coming across these reports a few years ago, I have stayed away from MK-7. You may want to consider a brand that contains only K2 MK-4.

 

[grenade]

K2 (I use health natura True K2 orally) helps me profoundly with depression, anxiety and mental clarity in a dose dependent manner. The more I take the better I'm off it seems. I'm up to 100-150 mg /daily lately and haven't seen any downsides. Is there something to worry about long-term with mega doses of K2?

Hey encerent,

I wondered the same thing myself, as I will be using 45 mg of topical K2 MK-4 daily for a couple weeks to resolve joint and bone spur issues.

Another user here did the same exact thing, had the issues resolve, and never saw any adverse effects.

It seems that very large amounts can cause heart arrhythmia. As user rzero said, MK-7 stays in the body for long, so that form of K2 would not be prudent for mega-dosing.

EDIT:
@haidut , care to chime in?

 

[sladerunner69]

Dose that high are clearly not immediately tosic, but over time will lead to nutrient deficiencies and imbalances...

 

[Giraffe]

In my practice, I've applied a simple principle for situations like this. (disclaimer: I don't know if this is Ray Peat practice or not, and is solely based on my opinion and experience) Start with loading does, that incrementally increase over time (minimum wait time: 6 weeks) till a state of optimization is felt, or a specific lab based benchmark is reached. In some instances, these doses can end up really high. Maintain this for 6-30 weeks, (depending on the situation) followed by incremental decreases till the lowest effective dose is reached. Time frames, wait times between increases/decreases, vary between substances, condition, and biological individuality. The important thing to remember is that loading doses and maintenance doses (if needed at all) can differ significantly. Also, lifestyle changes should be the primary foundation of care and recovery. Supplements, come from a foundation that they are meant to supplement, not replace, an appropriate diet and lifestyle. Otherwise we would call them replacements, not supplements.

In summary, loading doses if needed, possibly a large number of initial supplements and dietary changes may be needed to optimize the individual. Followed by the fewest number of supplements, and lowest possible effective doses for long term maintenance.

Peter, what kind of dose do you have in mind when you say "loading dose"? What do you mean with "increase over time" and "minimum wait time 6 weeks"? Can you give an example?

I have on/off bone pains in the shins, and last time I had access to a blood pressure monitor, the difference between systolic and diastolic blood pressure was quite large. Vitamin D seems to help with the bone pains (it definitely helps with mood), but does not completely solve the problem. (Magnesium, calcium, vitamin B6 and C are covered.) I have never felt anything from vitamin K2 up to doses of 5 mg per day. I am planning to try higher doses now. In your experience what could "a state of optimization" feel like? What are other symptoms/markers I would want to look out for?

 

[healthnatura]

Peter, what kind of dose do you have in mind when you say "loading dose"? What do you mean with "increase over time" and "minimum wait time 6 weeks"? Can you give an example?

I have on/off bone pains in the shins, and last time I had access to a blood pressure monitor, the difference between systolic and diastolic blood pressure was quite large. Vitamin D seems to help with the bone pains (it definitely helps with mood), but does not completely solve the problem. (Magnesium, calcium, vitamin B6 and C are covered.) I have never felt anything from vitamin K2 up to doses of 5 mg per day. I am planning to try higher doses now. In your experience what could "a state of optimization" feel like? What are other symptoms/markers I would want to look out for?

For vitamin K2 Mk4 I consider 20mg per day to be a loading dose. I usually do muscle testing or electrodermal conductivity testing to determine a baseline loading dose. K2 Mk4 ranges from 5-20mg/day for a loading dose. If the dose is 20mg, I build up to that over 4 weeks, starting at 5mg and increasing by 5 mg till 20 mg is reached. I have also just started doses right out at 20mg without any problems. I had an elderly patient with bladder stones, completely full of stones (over 300 of them), he had surgery to make them smaller and then we dissolved them with a course of K2 20mg/day and liposomal EDTA Max (3 grams, 3 times a week) for 60 days. He has degenerative scoliosis so I intend to keep him on 20 mg long term along with 10,000 iu daily of D3.

Not everyone will "feel" a state of optimization and it will depend greatly on age and condition. In your case, the bone pain may take a while to resolve, if vitamin K deficiency is a part of the problem. If the source of the pain is more structural than nerve, changes will take longer to notice, perhaps 6 months. Inflammation 2-6 weeks, low bone density 6-12 months, osteoarthritis 4-10 + months. People who use K2 Mk4 for mood, usually see changes within a few days to hours, because Mk4 absorbs into the nervous system so fast.

Hope that helps.

 

[Giraffe]

Hope that helps.

It answers my questions. Thanks.

 

[docall18]

I dont believe its a good idea to mega dose K2. I tried 30mg/day at one stage. However you need to make sure you get lots of D3 with it. Otherwise you will get insomnia, muscle pain, etc etc.