Can High Doses of Vitamin D Be Harmful?

Let me start with a question that lingered in my mind for a while:

​Has anyone ever died from too much vitamin D?

Even though vitamin D is a very safe substance, the unfortunate answer is yes, and, in a moment, you’ll understand why and how it happened.

But, does this mean you should be afraid of supplementing with vitamin D?

It depends.

To understand this seeming contradiction, let’s rephrase the question:

​Has anyone ever drowned at sea?

Unfortunately, the answer is also yes. According to the World Health Organization, drowning accounts for 360,000 annual deaths worldwide. (1)  But, let me ask you:

Does this mean you should be afraid of water?

If you are a mother and your child will be traveling with permissive grandparents, will you be afraid of knowing they’ll be taking many trips to an unsupervised pool? I’m sure you would.

But what if you could be present the whole time to make sure your child remained safe? What if you knew the pool would have several highly trained lifeguards on the watch the whole time? Now you’d feel much safer about the idea of letting your child play in the water.

The same is true about vitamin D supplementation. If you don’t follow the safety guidelines, you can hurt yourself.

We know that 360,000 people drown each year but how many die from too much vitamin D?

As it turns out, answering this question proved to be much harder – and far more surprising – than I expected.

I began this quest with a simple google query: “deaths caused by vitamin D supplementation”. What could be more straightforward than that?

Let us look at the results:

​Can you spot the pattern? 

I asked Google to tell me about deaths caused by vitamin D supplementation and its first result points me to a study telling me about how low vitamin D levels increase the risk of all-cause mortality. (2)

The second search result is even more enlightening because it links to a study (3) providing us with a visual representation of how vitamin D blood levels impact your general chances of dying:

​In a nutshell: Low vitamin D levels increase your chances of dying.

In the third search result we found a multinational group of researchers telling us that “supplementation with vitamin D3 significantly reduces overall mortality among older adults;” with the added warning: “However, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk.” (4)

​Or, in other words: “Just because vitamin D is good for you don’t go on and take as much as you like.”

Fair enough.

The fourth result is from WebMD. “A new study shows that people who have low levels of vitamin D in their blood had a greater risk of dying”, states the article. Later it says: “Researchers found that people with the lowest levels of vitamin D in their blood had the highest chances of dying.“ (5)

The pattern keeps repeating. Apparently, Google doesn’t index articles about vitamin D related deaths when you search for that exact phrase.

But, the fifth result really caught my eye:

​“Tragic death of baby highlights need for vitamin D public health policy change” is the title of the fifth search result.

When you read this title, what images come to your mind?

When I saw it, I imagined a poor mother losing her child due to some unexpected vitamin D side effects. This thought tightened my stomach. No Doctor should administer vitamin D to a baby without following the safety guidelines.

However, my first impression was wrong.

The article, from Science Daily, is about a baby who had died due to “complications of heart failure caused by severe Vitamin D deficiency.“ (6) A preventable death.

Still, this further supports our pattern: Vitamin D supplementation is associated with the prevention of health problems, not with death.

I won’t bore you with a detailed consideration of the following search results. If we really want to access vitamin D safety profile, we have to be more creative in our search terms choice.

Okay, it seems vitamin D probably won’t kill you but how much can it hurt you?

When ​researchers are trying to access the safety profile of a substance, ​they will often look at the LD50.

 What is the LD50 and why it matters?

​LD50 stands for “Lethal Dose 50%.” Or, in other words, the LD50 attempts to answer the following question: “If you had 100 test subjects, how much of this substance would it take to kill half of them?”

As you may imagine, this test is not carried out in humans. Instead, mice are used. Then, researches use their knowledge about the differences between human and mice metabolism to establish a relationship between their findings and their real-world application.

Just so you can get a better feel of how LD50 translates to real life, author Andy Brunning from CompoundChem.com shares this enlightening infographic:

Drink 6 liters of water at once and you are estimated to have a 50% chance of dying.

Now that we have a clearer grasp of the meaning of LD50 we must ask: How much vitamin D would you have to ingest at once to have a 50% chance of dying?

​Even though ​I couldn't find information on humans, tests ​performed on dogs point to an LD50 of 88mg/kg. (7)

How can we understand this number?

First of all, keep in mind this is an average value. Some dogs might be much more sensitive to vitamin D and, in their case, much lower doses could prove toxic or even fatal.

But let’s run with the 88mg/kg. Where does this number take us?

Imagine you had a group of dogs weighing around 10 kg each. If they were to take 88mg of vitamin D per each Kg of their body mass, it’s estimated that 50% of them would die.

Since they have 10 kg of body mass, this translates to a dose of 880mg of vitamin D. However, if a dog weighed 5 kg this dose would be 440 mg.

We are used to thinking of vitamin D in terms of International Units (Abbreviated “IU”). For example, a high-potency vitamin D bottle usually contains around 10,000 IU of vitamin D3 per gelatin capsule.

Can you guess how many IU you’d have to give to a dog to reach the LD50 value of 880 mg?

First, we need to know how many milligrams of a substance are in an IU, then you need to perform a simple multiplication.

This is not as linear as it seems. Why? Because there's no direct relationship between milligrams and international units.

​For example, 1 IU of vitamin D3 is equivalent to 0.000025 milligrams of vitamin D3, but one IU of vitamin A is equivalent to 0.0003 milligrams if it’s in the form of retinol or 0.0006 milligrams if we are talking about beta-carotene (8​).

In fact, international units are often used to represent such small values that we’d be better off thinking in terms of micrograms and not milligrams.​

​Comparison of the variations in the
measurement of international units

Now that we know 1 IU of vitamin D is equivalent to 0.025 micrograms we need to do some simple math:

If 880 milligrams equals 880,000 micrograms, and 1 IU equals 0.025 micrograms, then there are 35,200,000 international units in 880,000 micrograms.

Now, if 1 gelatin capsule contains 10,000 IU, how many of these capsules would you need to give a dog to reach LD50?

About 3,520 capsules, or 10 boxes containing 365 capsules each.

That’s a lot of capsules.

Even though this number applies only to dogs and not to humans, it allows us to understand that vitamin D can’t exactly be considered a dangerous substance.

But still, the questions linger in our mind: How toxic is vitamin D to humans?

To answer this question let’s look at the reported cases of vitamin D overdose. Or, in other words, we’ll be trying to answer this question: What happens when a human accidentally takes a massive dose of vitamin D?

We began this quest by asking Google to tell us about vitamin D related deaths, but Google couldn’t tell us of any case in its first page of results.

Given how Google results are derived from highly complex algorithms evolving artificial intelligence and machine learning, the fact that we are unable to find reports of a vitamin D related death in its first page is great news.

Of course, this doesn’t mean there were no deaths – there are -- but it’s a strong indicator of how rare such an event is.

Why is so hard to find information about vitamin D related deaths?

To answer this question, let’s look at what happens in the human body when you mistakenly take a massive dose of this substance.

​In the open access journal Einstein (São Paulo) there is this report of a man that had been taking 4,000,000 IU of vitamin D. (9)

Now, you might be thinking:

“4 million? That’s 400 capsules per day. How is that even possible?”

Well, that’s true, except he wasn’t taking 400 capsules a day. He was taking just one. It just so happens that those capsules had come from a compounding pharmacy. This man entered the pharmacy with a medical prescription for 2,000 IU capsules and left with capsules containing 4 million international units of the vitamin.

How did this happen?

It happened because the pharmacy in question prepared the capsules itself. These are called compounding pharmacies and work just like a regular pharmaceutical laboratory, but, as it seems, with a harder to enforce quality control.

The study tells us he had been taking these capsules for several months, however, we can’t know how many of them contained four million IU instead of the expected two thousand IU. Nevertheless, we do know his blood levels of vitamin D upon his admission.

But, before I tell you how much vitamin was in this man’s blood, it’s important that I give you a baseline number for comparison.

When your Doctor orders a vitamin D blood test – the famous 25(OH)D3 test -- he’s interested in measuring how many nanograms of this vitamin are present in each milliliter of your blood.

This doctor will usually be happy if your levels are between 20 and 80 nanograms per milliliter – ng/mL. If they are above 100 ng/mL he’ll become worried and if they are greater than 150 ng/mL he’ll most likely panic – unless, of course, he’s familiarized with high-dose vitamin D protocols, such as the Coimbra Protocol.

Now please, put yourself in the shoes of the Doctor that first saw this result:

1000 ng/mL.

That was the level of vitamin D in that man’s blood. It’s one of the highest levels reported in the scientific literature in what concerns vitamin D supplementation.

“How was this man even alive?” the medical team probably thought.

Well, he was alive for sure, but he wasn’t asymptomatic. Fortunately, he was in the hands of good Doctors and was promptly treated.

Nevertheless, before treatment, how were this extreme levels of vitamin D affecting this man’s health?

Before we answer, it’s important to keep in mind that vitamin D, in itself, is pretty much harmless. The reason why vitamin D can become problematic is related to how it impacts calcium and phosphorus metabolism, as well as your parathyroid glands.

Due to several hormonal and chemical interactions, calcium and phosphorus blood levels will rise, while the parathyroid glands secretion of parathyroid hormone will be expected to come down.

This will lead to a serious health problem called hypercalcemia. Symptoms of hypercalcemia include extreme thirst, frequent urination, constipation, mental confusion, and cardiac problems, among many other related symptoms​. (10)

Unattended hypercalcemia may even prove fatal.

​That’s why our body is well prepared to regulate its own calcium levels.

​When mineral levels increase, our kidneys become responsible for restoring the correct values again. They do this by working even harder at filtering the minerals found to be in excess from our blood.

But there’s a limit to how much calcium a kidney can filter.

That’s why medical professionals performing high-dose vitamin D therapy are much more interested in your calcium levels and in your renal health than on your vitamin D levels.

In fact, when we speak about the dangers of vitamin D supplementation, we are mostly speaking about the potential of vitamin D to raise calcium to a harmful value and cause hypercalcemia.

Back to the man, he had 1000 ng/mL of vitamin D in his blood.

How much harm could this level of vitamin D cause him?

It depends a lot on how well these man’s kidneys were functioning.

And, as it turns out, he was no healthy person. He had a history of diabetes mellitus, hypertension, non-dialysis chronic renal failure, and smoking.

From these 4 problems, can you guess what’s the most interesting one to our investigation?

Non-dialysis chronic renal failure.

​This man had severe kidney issues. Keep this mind.

At 1000 ng/mL this man was experiencing a worsening of his renal function (this was to be expected as his frail kidneys were working harder and harder to try and excrete the calcium in excess), pruritus (a fancy name for itchiness), muscle weakness, lack of appetite and weight loss.

His calcium levels were measured and found to be well above the upper limit of the normal range. Upon closer examination, renal calculi (kidney stones) were also detected. One of these was causing an obstruction. The man had to undergo surgery to remove it.

Had this man failed to look for medical help and he could have died. He would have been killed not by vitamin D, but by the calcium buildup promoted by it. It took him 9 months for his blood work to return to normal levels.

But…

Keep in mind that his symptoms weren’t being caused directly by the high levels of vitamin D.

Instead, his symptoms were the result of the calcium build up promoted by vitamin D. If he had perfectly functioning kidneys, he would have had a smaller concentration of calcium in his blood and, by extension, milder symptoms.

Also, had he been following the daily safety guidelines, which include a low-calcium diet, drinking at least 2.5 liters of fluids per day, taking vitamin D co-factors like magnesium and vitamin K2, and his outcome might have been much different.

Still, his circumstances serve to highlight the safety profile of vitamin D.

After all, if there’s anything we learn from this case is that it’s possible to have serious kidney problems take a ridiculously enormous amount of vitamin D, ignore all the safety guidelines and still live to tell the tale.

All things considered, the team of researchers wrote in their paper: “the estimated toxic dose of vitamin D should be greater than 100,000​ IU per day for, at least, one month.” (10)

This means that, if you are healthy and don’t suffer from a hypersensitivity to vitamin D, you will probably survive a dosage of 100,000 IU per day for less than a whole month, even if you fail to pay attention to the remaining safety guidelines.

Still, I wouldn’t recommend such high-doses, unless they are being prescribed by a knowledgeable physician.

Take the example of the pioneer of high-dose vitamin D treatment: Dr. Cícero Coimbra.

Even though Dr. Coimbra is known to have prescribed up to 200,000 IU of vitamin D, this has been done only in very specific cases.

When you undergo a high-dose vitamin D protocol like the Coimbra Protocol, you are first prescribed a much lower dosage. Then, after 2 or more months, your calcium levels in both your blood and your urine are tested, along with several other parameters. Then, your dose is adjusted accordingly.

In certain cases, the person undergoing treatment proves to be more resistant to vitamin D than expected. Maybe the person is very muscular or overweight. This, coupled with problems along the chain of events that culminates in the activation of vitamin D, may force the Doctor to keep increasing the dosage of vitamin D until, in rare cases, a dose of 200,000 IU is reached.

Even then, such a dose will only be supplemented under tight medical control and to a patient well informed about the necessary safety guidelines.

Why is tight medical control so important when using such a high dose?

Because your calcium levels may end up rising too much. When this happens, if you want to keep your high-dose, you’ll end up being prescribed specific diuretics – to help your kidneys expel the excessive calcium -- or bisphosphonates – which directly influence your bones interaction with calcium.

These drugs may have side-effects. Bisphosphonates, for example, may cause your jawbone to enter a state of necrosis — or "rotting". This happens because of how bisphosphonates will reduce the body's ability to renew bone tissue.

​Ana Claudia Domene, a patient of Dr. Coimbra, describes how some patients end up reaching 4000 ng/mL of vitamin D in their blood!

​​And we thought that 1000 ng/mL was impressive!

If you answer yes to all these 3 questions, then you don’t need to worry too much about vitamin D supplementation.

As we’ve seen in our investigation, if you have healthy kidneys, you could probably survive 100,000 IU per day – for less than 30 days. But why would you do it? Vitamin D supplementation isn’t about how many IU you can endure. This is not a competition to check who can make more points. It’s all about finding the right dose for you.

If the right dose for you is 10,000 IU, then 100,000 IU can only hurt you. But, if you are resistant to vitamin D, 10,000 IU is a negligible amount and you’d need much more. Probably about 1000 IU per kg of body mass. But, even then, such a dosage would be reached after several months of careful monitorization.

Now, there’s just one question we still need to answer: As anyone ever died from a vitamin D overdose?

Unfortunately, the answer is yes.

​It took some googling, but I did find a report from the Times of India about a young boy who fell victim of the ill-informed choices of a – I want to believe – well-intentioned Doctor. (11)

The year is 2006. The unnamed boy is 10 years old and lives in Delhi, in northern India.

Apparently, this boy’s Doctor was worried about his growth rate so, according to the news source, prescribed him “six lakh international units (IU) of vitamin D daily for 21 days.” (1​2)

​It was these “six lakh” of vitamin D that ​proved fatal for the young man.

​“A lakh is a unit in the Indian numbering system equal to one hundred thousand.” (​13).

In English, we read the number 100,000 as “one hundred thousand.” Also, notice how the comma is used to divide up the number in groups of 3 digits. In the India numbering system, however, this same number would be written as 1,00,000 and it would be read aloud as “one lakh”.

This boy was prescribed 6 lakh IU, or 6,00,000 IU in the Indian numbering system. Yes, that’s a full six hundred thousand international units per day, every day, for 21 days. This kid was only 10 so we can assume he had around 30 kg​ (1​4), perhaps even less, if we consider that the very reason he was prescribed vitamin D was that he had growth issues.

This low weight is a relevant factor. Why?

If you recall, the toxicity of a substance is expressed in milligrams per kilogram (mg/kg). That makes sense. After all, the higher your body mass the more vitamin D you need to fill up all that conglomerate of fat and muscle.

A simple thought experiment illustrates this point well: Imagine you have two packets of sugar and two cups with coffee. One of the cups is holding 50 ml of coffee, but the other one holds a full liter. It’s an enormous cup.

Each packet contains around 7 grams of sugar. You open the first packet and pour the sugar in the 50 ml cup. You mixed it well.

You grab the second packet and pour the sugar in your liter-sized cup.

Each of these cups has the same amount of sugar: 7 grams. However, the small cup as a concentration of about 140 mg of sugar per milliliter of coffee. The bigger cup, on the other hand, has a meager 7 mg of sugar per milliliter of coffee.

The same thing happened to our small boy. For his young system, 600,000 IU of vitamin D every single day was just too much.

Just how much?

If you follow Dr. Coimbra baseline ration of 1000 IU per kilogram, this means a boy weighing 30 kg would be taking 30,000 IU of vitamin D – provided, of course, that his kidneys were healthy, and his blood work remained stable.

You would have to weight a full 600 kg to be prescribed 600,000 IU. That’s how much an American Bison weights! (1​5)​​​​

If you wanted to duplicate this prescription using a bottle containing 10,000 IU capsules, you’d have to take 60 of them, every day, for 21 days. That’s more than ​an 100 capsule bottle ​every two days.

​To put things in ​even more perspective, ​my wife took ​this photo of me holding 60 gelatin capsules of vitamin D. Each ​with 10,000 IU. That's how many I'd ​have to take every day​.

First, that such a thing can’t be repeated.

Vitamin D can only be taken in a high-dose by a person who knows about the safety guidelines and is willing to follow them. Then, this person’s health must be closely monitored.

Also, these high-doses need to be reached over a period of several months.

We also learn that even though vitamin D isn’t exactly dangerous, it isn’t harmless either.

You must respect it, just like you respect the sea. You wouldn’t leave your small child alone at sea. However, you would be fine with the idea of him playing in ​a pool, under the supervision of a competent lifeguard.

​That’s the kind of respect we need to nurture for ​vitamin D.