In the last two blog posts, we’ve seen how important vitamin K2 is for osteoporosis and atherosclerosis, in that K2 moves calcium from the blood vessels to the bones. Today we’ll explore K2’s connection to prostate health and varicose veins. Seems an odd combination – but read on!  

Poor prostate health is pervasive in Western society, particularly with advancing age. The condition Benign Prostate Hyperplasia (BPH) – enlargement of the prostate gland – is seen in nearly all men once they reach their 70s and 80s.

Yet, after years of research, there is still no clear understanding of what is the root cause of BPH. Several risk factors have been identified, such as obesity, diabetes, and metabolic syndrome. Testosterone is obviously involved too, but levels of testosterone decrease with age, while BPH incidence increases with age. Also, serum testosterone levels don’t correlate with the severity of BPH either, so it’s not a clear testosterone relationship.

What might BPH have to do with varicose veins?

Recent work by Gat et al. takes a fresh look at BPH. They found in one study that BPH does not occur without a varicocele. What is a varicocele? While a varicose vein is a swollen, twisted leg vein, a varicocele is a swollen, twisted vein in the scrotum. 

This swelling in the vein affects the one-way valves in these veins. The research has shown that this causes failure of the valves, resulting in backflow of blood back to the testes. Rather than the blood flowing up into the spermatic vein, the backflow blood is emptied through the prostatic vein. This means that the blood reaching the prostate has much higher testosterone levels than normal. In fact, with varicocele, testosterone levels in veins around the prostate are seen to be 130x higher than overall circulation levels.

These high testosterone levels can then lead to hyperplasia/enlargement in the prostate and thus BPH. And might also affect the risk of prostate cancer.

Take a look at the picture at the top of this blog post, which illustrates this. The left-hand side shows normal veins – no varicocele and blood flowing from the testes (T) up, so no backflow to the prostate. The right-hand side diagram illustrates varicocele and the valves from the testes not functioning. This leads to backflow to the prostate gland (P) and enlargement of the gland. (Diagram from Gat. et al., 2008).

So what causes varicocele and varicose veins?

The role of vitamin K2 in vein/arterial health has been studied – as we saw with K2 deficiency associated with atherosclerosis. With K2 insufficiency, the artery and vein walls can become calcified, setting the stage for varicosities to form.

So is poor prostate health due to a vitamin K2 deficiency that ultimately leads to hyperplasia?

Evidence shows us that the protein MGP that we discussed in our first K2 blog post is seen to be over-expressed in varicose vein tissue, compared to normal vein samples. (As a reminder, Vitamin K2 acts in association with certain proteins that are calcification inhibitors. Three of these are called Osteocalcin, Matrix Gla Protein (MGP), and Gas6. MGP is the strongest inhibitor of soft tissue calcification presently known. But for these proteins to do their job and get the calcium into the correct parts of the body, they need Vitamin K2 to activate them.)

The form of MGP found in the varicose veins was the inactive form, i.e., it hadn’t been activated by K2. In contrast, MGP found in the normal veins was mainly the activated form. The level of varicosity seems to also be dose-dependent on vitamin K levels. This suggests that vitamin K2 deficiency might be associated with varicose veins and might also be a factor in varicocele.

Does this K2 involvement with prostate health extend beyond BPH to prostate cancer?

Results from the large European epidemiology study (EPIC study) in 24,000 men and women between the ages of 35 and 64 found that independent of other cancer risk factors, people with the highest average intakes of vitamin K2 were ~30% less likely to develop cancer than people with the lowest intake.  K2 intake was more strongly inversely associated with fatal cancer rather than with cancer incidence. What was interesting is that this association was stronger in men than in women. This led researchers to investigate the two most common cancers in men – prostate and lung cancer. 

In the Heidelberg cohort of the EPIC study, researchers found that while men with the highest levels of K2 had an overall lower risk of getting prostate cancer (35% risk reduction), this effect was not statistically significant. But where K2 did seem to have a more powerful impact is on the risk of advanced stage and high-grade aggressive cancer (63% risk reduction with highest levels of K2). So K2 intake might make a difference for risk of aggressive prostate cancer.

One issue with the EPIC study – and many other epidemiology studies – is that food frequency questionnaires were used to determine vitamin K2 intake. This approach is fraught with inaccuracies – not just with people’s recall of what they eat, but also the amount eaten by a person doesn’t give us information on how much is absorbed by that person’s body.

However, one study looked at a blood marker of vitamin K2 levels to get around the food frequency questionnaire limitations. Their results showed the same trend as the EPIC study, namely that K2 deficiency (as measured by serum biomarkers) doesn’t affect overall risk of developing prostate cancer, but is significantly associated with advanced-stage prostate cancer. 

Vitamin K2 for prostate health: the missing link?

The research on K2 and prostate health is summarized in an interesting Medical Hypothesis article authored by Michael Donaldson.  

He hypothesizes that the evidence today suggests that poor prostate health is essentially a vitamin K2 insufficiency disorder. The insufficiency leads to calcification of the vein walls through the presence of inactivated MGP, leading to the formation of a varicocele. Blood then does not flow normally; rather it goes directly to the prostate resulting in high levels of testosterone in and around the prostate which can result in BPH and increase the risk of prostate cancer. 

Sufficiency of vitamin K2 might be a key factor. Yes, further studies are needed to confirm these findings. But because supplementation with K2 is low risk with good potential benefits, supplementation with K2 might be warranted for you if you are suffering from prostate issues. Talk to your urologist or health care practitioner about it. Remember, K2 is just one factor…there’s also vitamin D, calcium, magnesium, vitamin A, a healthy diet, exercise…

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