Vitamin D3 and K2: The Benefits, Differences, and Usage

Many people, when they think of vitamins, first think of the letters. Vitamin A, vitamin C, vitamin D; and some have numbers attached like vitamin B12. All vitamins have more than one form, similar in chemical structure but different enough that they can have different biological reactions and uptake.

When you're considering taking supplements, understanding not just the vitamin, but its specific form – and how that form interacts with other vitamins – can be an important part of making sure you're achieving your goals with the supplements you take.

Two of the more popular vitamin supplements on the market today are Vitamin D3 and Vitamin K2. These specific forms of vitamins D and K are purported to have a handful of beneficial effects, but the question is, is there research to back it up? If so, should you consider taking them, and should they be taken together, separately, or one or the other?

Let's talk about it.

All About Vitamin D

Most people know vitamin D as the "sunlight vitamin." It's the vitamin your body synthesizes naturally when exposed to sunlight, and a common supplement in the colder months, when the skies are overcast and you're more likely to be spending time indoors. Of course, people being who they are, many have chosen to megadose vitamin D to try to make up for any deficiency.

Note: Megadosing any vitamin or supplement has inherent risks. Your body needs various vitamins and minerals, but too much of a good thing can be harmful. Unless you've been diagnosed with a deficiency and your doctor has recommended a large dose of vitamin, make sure you're aware of the potential side effects before you try it.

Vitamin D comes in at least five identified forms, appropriately named D1 through D5. The version we're primarily talking about today, D3, is also known as cholecalciferol. It's absorbed in the small intestine, primarily alongside dietary fat, and is generally maintained throughout your life (that is, it doesn't decrease absorption as you age like some other vitamins and minerals.)

Vitamin D deficiency can lead to long-term problems. In children, it can cause rickets; in adults, it causes osteomalacia or a softening of the bones. Normal levels are relatively easy to maintain, however, and global diets tend to be fortified already. Overly high levels of vitamin D can also cause side effects, including things like:

• Hypercalcemia
• Hypercalciuria (and kidney stones)
• Nausea, vomiting, and muscle weakness
• Dehydration, polyuria, and excessive thirst

In very extreme overdose levels, vitamin D toxicity can even lead to renal failure, cardiac arrhythmia, and even death.

Why do people supplement vitamin D?

Over the years, numerous studies into the effects of vitamin D have shown a variety of potential benefits. Other studies, though, have either failed to replicate those benefits or have been statistically insufficient to draw a real conclusion. 

The benefits usually cited include:

• Bone support. Since one of the primary functions of vitamin D is to help transport calcium throughout the body, supplementing vitamin D is thought to help ensure an appropriate level of calcium in the bones, particularly as you age. A meta-analysis of supplementation studies found inconclusive evidence as to whether or not this works.
• Cancer prevention. As a class of disease, cancer is one of the greatest boogeymen of our modern medical system, so anything with the potential to reduce the incidence of cancer in the population is a good option. One study seemed to indicate an inverse association between vitamin D levels and cancer rates – in other words, decreased cancer incidence with higher levels of vitamin D. Unfortunately, further studies found no similar correlation.
• Cardiovascular health. Much like with cancer prevention, there was one study that seemed to suggest higher levels of vitamin D could reduce the risk of cardiovascular disease; however, further studies were unable to find similar correlations and saw no difference between those who supplemented and those who didn't.
• Vitamin D is commonly used in various brain processes, so some studies have been performed looking into the association between vitamin D levels and depression. Observational studies indicate some correlation, but clinical trials have not supported the same conclusions and show no significant reduction in symptoms.

There are other proposed benefits as well, but the pattern is largely the same.

Since I work indoors and wear sunscreen, I’ve elected to supplement with 1,000-2,000IU of Vitamin D3 as part of MicroVitamin(link). But just because I take a supplement does not in any way mean that you should as well.

Unless you're at risk of deficiency like I am, supplementing additional vitamin D is unlikely to have significant benefits.

As for why D3 over another form of vitamin D, it's simply the most common and most readily bioavailable form of the vitamin. A common problem in supplementation is that the form of the vitamin you take may not be usable as-is by the body, so taking more of it doesn't provide any benefit without some underlying addition to help your body absorb it.

All About Vitamin K

Vitamin K is an entirely different group of molecules from vitamin D. Vitamin K is another fat-soluble vitamin and is primarily used in blood coagulation and in calcium control throughout the body. This calcium control is a big part of why vitamins D and K are often discussed together, though they are chemically very different and operate in different ways.

Vitamin K2, the one we're looking at primarily today, is one of three main types of vitamin K. It's common in animal products and fermented foods. The most commonly supplemented version today is MK-7, a long-chain menaquinone, most commonly found in fermented foods as a bacterial byproduct.

Why do people supplement vitamin K?

Like vitamin D, there have been studies to indicate the benefits of vitamin K and others that fail to replicate it. In fact, most of the studies that show strong benefits from vitamin K supplementation are decades old and have since been retracted for being problematic in some way.

That said, a more recent study looked at two possible effects of vitamin K: overall blood vessel health and myocardial infarction. While the first showed no conclusive change, the latter showed a possible significant risk reduction.

Vitamin K2 is taken over other forms of vitamin K for similar reasons as D2; it's the most bioavailable form you can find readily available.

Supplementing Vitamin D and K Together

Now we come to the crux of the issue: a new study issued in November of last year. This study looked at the combined supplementation of both vitamin K2 and vitamin D3. The goal was to examine if there is any benefit to arterial valve calcification. The theory is simple; these two vitamins help the body transport calcium to the bones. Since calcium building up in blood vessels and arteries is what causes coronary artery calcification, perhaps supplementing these vitamins could keep more calcium in the bones and away from the arteries.

In this study, a total of 389 participants were randomized, with some given a placebo and some given the vitamins. They were tracked over two years and the process of coronary artery calcification was monitored. In total, there was no significant change in the progression of CAC, but there was a potential reduction in worsening obstructions.

All of this sounds minimal and cautious because it is. The study authors themselves say:

"Although the primary endpoint is neutral, differential responses to supplementation […] and in safety endpoints are hypothesis-generating for future studies."

In other words, this particular study didn't conclusively prove a benefit but opens up additional options to test for other beneficial results that may exist.

Indeed, some of these additional possible studies are currently ongoing. We won't have results for some time, but they're worth watching.

Should You Consider Supplementing Vitamins D3 and K2?

At the end of the day, everyone wants someone to be able to tell them what the best course of action is for their health. That's not my role here. It's a discussion you need to have with your doctor and a decision you need to make for yourself.

My goal here today is to provide a robust picture of our current medical understanding of how these vitamins interact with the body, the potential effects they may have, and their limitations.

With that in mind, let's run down the list.

Does vitamin D support bone health and strength? Not really. As long as you're not deficient in the vitamin, there's no conclusive evidence to suggest that taking more vitamin D will strengthen bones. Most studies performed looking at this impact find no significant difference between those who supplement and those who do not, in terms of incidence rates for fractures and osteoporosis.

Does vitamin D help reduce the incidence of cancer? Results are mixed. It's important to remember that "cancer" is an entire class of diseases, and different types of cancer respond in different ways to different things. As it stands, current studies and evidence are inconclusive. It's possible that maintaining adequate levels of vitamin D could reduce cancer mortality rates, but further research is needed.

Does vitamin D reduce the incidence of cardiovascular disease? This is where things get tricky. A large observational study in Denmark found that both too-low and too-high levels of vitamin D may be associated with a greater risk of mortality from cardiovascular disease and related issues. On the other hand, clinical trials are more mixed, with some showing a reduction in cardiac failure, but not other forms of cardiovascular disease. In short: it seems most important to stay within a normal range, neither too high nor too low.

Does vitamin K support bone health and strength? Much like vitamin D, results are mixed and inconclusive. Some studies found a link between vitamin K supplementation and bone health; others did not. Vitamin K has been authorized as a treatment for osteoporosis in Japan, parts of Asia, and the EU, but not in the USA or elsewhere around the world. Most such studies also supplemented with calcium at the same time, making it difficult to tell if vitamin K or calcium is responsible for the observed effects.

Does vitamin K reduce the incidence of cardiovascular disease? This one is very tricky to analyze. There are a variety of ways that cardiovascular disease can manifest, from arterial hardening to congestive heart failure to stroke to myocardial infarction. Different studies have found different impacts of vitamin K on these different cardiac diseases. The end result is that, as of right now, there's no conclusive evidence to support vitamin K as a benefit to cardiac health; however, certain studies have had promising results that warrant further study, and those further studies are ongoing.

If cardiovascular issues are your primary concern, it's possible that these vitamins could have some beneficial effects, but more studies are ongoing to say one way or the other. It's also possible that they might do the opposite. Additionally, if you're currently on medications such as Warfarin, antibiotics, bile acid sequestrants, orlistat, statins, steroids, or certain diuretics, taking these vitamins can have negative interactions.

The choice of whether or not to take a supplement depends on your own personal health circumstances and the advice of your doctor. I'm just here to present the evidence as we currently understand it.

Do I supplement with Vitamin D3 and K2?

As mentioned in this article, I supplement with 1,000-2,000IU of Vitamin D3 since I’m at risk of deficiency. The evidence for improved bone density from Vitamin K2 intrigues me, and there are possible cardiovascular benefits from Vitamin K2. As such, I’ve elected to also supplement with Vitamin K2 in the MK-7 form at 90mcg as part of MicroVitamin.

Please remember however, that just because I take a supplement does not mean that you should as well.

Sources:

1. Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: Evidence Report and Systematic Review for the US Preventative Services Task Force: https://pubmed.ncbi.nlm.nih.gov/29677308/
2. Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: a systematic review and meta-analysis: https://pubmed.ncbi.nlm.nih.gov/24036014/
3. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease: https://pubmed.ncbi.nlm.nih.gov/30415629/
4. Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: dose-response meta-analysis of prospective studies: https://pubmed.ncbi.nlm.nih.gov/28251933/
5. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease: https://pubmed.ncbi.nlm.nih.gov/30415629/
6. Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494092/
7. Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT: https://www.jacc.org/doi/10.1016/j.jacadv.2023.100643
8. Vitamin D Fact Sheet for Health Professionals: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
9. Vitamin K Fact Sheet for Health Professionals: https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/