Vitamin K intake vs heart disease and all cause death

And a few other things, even PC!

Hi guys. I just saw this study- NOT an RCT however- and thought it might be of interest to some of us.

Some of us take vitamin D supplements based on a reasonable likelihood that it might help fight various cancers and help with over all health. A few more of us also take vitamin K2 on the likelihood that it increases the chances that calcium- the absorption of which is supposedly increased when D is supplemented(or lots of sunshine)- ends up where we want it, i.e. the bones and not out coronary arteries, aorta, and a few other places, where we don't want it.

So, this was not an RCT(there are some RCTs later), however, the evidence appears very interesting. Also, keep in mind that these studies are looking at "intake", which probably means mostly from diet and not from supplements! So who knows if supplements would be any good.

"We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. .............".

So they somehow judged the intake of Vit K, and then looked at various clinical outcomes over about 10 years. As usual, this is more associaton of increased intake vs improved outcomes, so no solid proof. But, the middle tertiary of K2 did better than the lowest, and the top group did better than the middle group. And K1 had no effect on CHD or all cause death. All of which is good enough to make these results highly interesting to me. Hence, I will continue to keep taking K2 until some harm is proven or it is proven useless. YMMV, of course.

"The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]".

So, risk of CHD in the middle group is 27% lower than the risk of the lowest K2 intake, and the highest third had a reduction of 57%.

Also, when all cause death was looked at as well as aortic calcification, the results were similar, and continued to improve with the higher intakes of K2(but not K1).
"Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.".

So, all cause mortality 26% less with the highest intake of K2, and severe aortic calcification 52% less.

https://www.ncbi.nlm.nih.gov/pubmed?term=(((geleijnse%20jm)%20and%20vermeer%20c)%20and%20menaquinone)%20and%20rotterdam

There was also this, which was similar over all, although K1 seemed better for cardio than K2:
https://www.ncbi.nlm.nih.gov/pubmed/24647393
" In longitudinal assessments, individuals who increased their intake of phylloquinone or menaquinone during follow-up had a lower risk of cancer (HR: 0.64; 95% CI: 0.43, 0.95; and HR: 0.41; 95% CI: 0.26, 0.64, respectively) and all-cause mortality (HR: 0.57; 95% CI: 0.44, 0.73; and HR: 0.55; 95% CI: 0.42, 0.73, respectively) than individuals who decreased or did not change their intake.............An increase in dietary intake of vitamin K is associated with a reduced risk of cardiovascular, cancer, or all-cause mortality in a Mediterranean population at high cardiovascular disease risk."

Post Edited (BillyBob@388) : 5/18/2019 7:00:52 PM (GMT-6)

And this vs PC:
https://www.ncbi.nlm.nih.gov/pubmed/18400723
"OBJECTIVE:

We evaluated the association between dietary intake of phylloquinone (vitamin K1) and menaquinones (vitamin K2) and total and advanced prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition...........................................................................................
RESULTS:

During a mean follow-up time of 8.6 y, 268 incident cases of prostate cancer, including 113 advanced cases, were identified. We observed a nonsignificant inverse association between total prostate cancer and total menaquinone(K2) intake [multivariate relative risk (highest compared with lowest quartile): 0.65; 95% CI: 0.39, 1.06]. The association was stronger for advanced prostate cancer (0.37; 0.16, 0.88; P for trend = 0.03). Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat. Phylloquinone(K1) intake was unrelated to prostate cancer incidence (1.02; 0.70, 1.48).".

However, this study showed no association at all for Vit K and PC:
https://www.ncbi.nlm.nih.gov/pubmed/30624568

Post Edited (BillyBob@388) : 5/20/2019 6:38:51 AM (GMT-6)

And for some here who are concerned with bone loss as a side effect of treatment, in addition to vitamin D, have you talked with your doctor about vitamin K2? Here is another RCT on K2 vs bone health

https://link.springer.com/article/10.1007/s00774-013-0472-7
"Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women

Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial. ......................

The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6–12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects.......".

Trailguy, you are welcome. I was surprised to find a couple of RCTs, one forbone health and one for aortic stenosis.

NotBubba said...
So solid research suggests an inverse association between the intake of K2, and prostate cancer and also CHD. And further studies of dietary vitamin K and prostate cancer are warranted.

But no one cares because "its all snake oil", can someone explain to me how that is?

It does appear to me that there is some fairly solid evidence of health benefits in several areas, including benefits to K1 as well as K2. But of course, more studies are always needed and they will come at glacial speed. And as usual, these studies I have come upon, until I went looking it, was mostly unheard of by me. I certainly never heard of any possible advantages of dietary vitamin K intake or supplementation from a doc or from normal news.

And, maybe that is because we still don't have large scale "proof". Sure, there are some RCTs, and many observational studies providing strong evidence in most cases( I also found some showing no evidence), but I think all my RCTs were positive, if not always of the good old "statistical significance(SS)". But that's OK, there is also no proof of harm, it is cheap, and there is enough evidence for me until proven otherwise. Good enough for me. YMMV. As we say on my hiker forums: HYOH, or Hike your own hike.

But it does make me scratch my head how there could be, for example, an RCT showing SS for what was it, less bone loss? And another SS for(with K1) less aortic stenosis(Both of those are pretty big deals!), and never heard a word about it on the news? Or from my wife's docs in her fight against osteopenia? Even if more studies are needed, since risk and cost are low, why the heck would this not be considered good news with docs informing us about it until larger studies disprove it, if they ever do?

Hopefully we won't wander off into some big battle about this general subject, but I admit to the occasional cynical thought as to why these studies are rarely pointed out by our docs or mainstream news sources. I mean, come on, there exist some RCTs confirming lots of associations! Until there are RCTs proving otherwise- or unless some one can find big problems with the studies- that should be big news! For those for whom all of the huge associations are not enough, there are actually some RCTs to confirm the associations. Just as there are for some other non-prescription, low cost, low SE, non-prescription interventions. I don't ever understand why these things are not of more interest. At least of more interest to us patients. But, again, HYOH, so to speak.

Post Edited (BillyBob@388) : 5/20/2019 3:34:55 PM (GMT-6)

A 2018 review of studies on vitamin K2 vs cancer:
"
5. Discussion

The present review summarizes the effects of VK2 on cancer in clinical, in vivo, and in vitro studies. Clinical trials demonstrated that VK2 has the potential to improve the prognosis of patients with cancer. In addition, evidence indicates that VK2 treatment can prevent HCC(liver cancer) in patients with hepatic cirrhosis, and the dietary intake of VK2 can decrease the risk of developing cancer, particularly prostate and lung cancer (54). Furthermore, VK2 is confirmed to restrain tumor cell growth in animal studies (1,7,20–22,55), with cell-cycle arrest and apoptosis involved in this inhibition. In vitro studies (1,23–27,35) certified that VK2 could inhibit the growth of several cancer cell lines. Although several detailed links remain to be investigated, studies included in the present review (23–25,33–37,39,41,45,48,49) indicated that induction of the cell-cycle arrest, cell differentiation, apoptosis, and autophagy is crucial for VK2-dependent suppression of cancer cell growth. Certain protein kinases, such as PKA and PKC, signaling pathways, such as the MAPK pathways, transcription factors, such as NF-κB and AP-2, and essential proteins, such as Bak and Cx43, are involved in the mechanism of VK2 activity against cancer cells (23,24,33,37,41). The combination treatment of VK2 with other chemotherapeutics, such as sorafenib, can exert a synergistic effect and reduce adverse drug reactions.

In conclusion, VK2 can positively inhibit cancer cells. VK2 appears to be an extremely promising agent with very limited toxicity, which can be a useful option for prevention of cancer and clinical therapy of cancer. However, the inhibition of vitamin K and D in cancers indicated that vitamins might have positive effects on the prevention and therapy of tumors. Therefore, the effects of vitamins or minerals on tumors should be investigated further.............
".
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5958717/

NotBubba said...
So solid research suggests an inverse association between the intake of K2, and prostate cancer and also CHD. And further studies of dietary vitamin K and prostate cancer are warranted.

But no one cares because "its all snake oil", can someone explain to me how that is?

When there is some actual proof i.e. a RCT wake me up.

To make this a little easier to sort out, and for folks who will only consider evidence from RCTs, here are the 2 RCTs linked to in the previous posts:

Vitamin K1 supplements vs aortic stenosis from calcification. I'm sure some of us have excessive calcium deposits in our small coronary arteries, as well as the aorta, that BIG artery:
https://www.ahajournals.org/doi/pdf/10.1161/circulationaha.116.027011
"Over the 12-month period, the AVC volume score progressed by 10.0% in patients in the vitamin K group compared with 22.0% in the placebo group (Table), representing a significant attenuation of AVC progression by vitamin K compared with placebo.........................................................
The present study is the first randomized controlled trial in men to demonstrate that vitamin K supplementation might decelerate the progression of AVC. Our findings are clinically meaningful because a strong, significant correlation exists between the AVC volume score and functional valvular parameters such as mean gradient or peak flow velocity............................................
We consider the present study results to represent the first proof of concept in the evaluation of the potential anticalcification effects of vitamin K treatment in human calcific aortic valvular disease. We acknowledge that our results need to be confirmed and should therefore be interpreted with caution"

And here is one related to bone health, since some PC treatments have a negative effect on that:
https://link.springer.com/article/10.1007/s00774-013-0472-7
"Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial.........................
The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6–12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects."

So there you go, 2 RCTs showing significant benefit from vitamin K supplementation, confirming a much large # of observational studies showing some evidence that diet higher in both K1 and or K2 had better health in a variety of areas.

Post Edited (BillyBob@388) : 5/22/2019 10:30:32 AM (GMT-6)