[1] Introduction.
The vitamin K family (name is from the German: Koagulationsvitamin) consists of vitamins that are needed for blood coagulation. Vitamin K is also involved in calcium transport to bone. (Vitamin K modifies certain proteins in a way that allows calcium to bind to them.)
- Vitamin K1 (phylloquinone, phytomenadione, or phytonadione) – from plants (leafy greens). Has a very short half-life in the body.
- Vitamin K2 (menaquinone) – from animal sources.
- MK-1
- MK-2
- MK-3
- MK-4 menatetrenone – can be synthesized in the body from K1. Short half-life.
- MK-5
- MK-6
- MK-7 cannot be produced by the body, except that e coli in the colon can contribute a minimal amount (from K1). Has a long half-life. This is the important one, IMO.
- MK-8
- MK-9
- three synthetic forms of vitamin K are vitamins K3 (Menadione), K4 (a synthetic hydrophilic menadione compound, clinically used for hemostasis), and K5,.
[2] Vitamin K1 & K2.
The Heidelberg cohort of EPIC (the European Prospective Investigation into Cancer and Nutrition):
[2a] (2008 – Germany)
“We evaluated the association between dietary intake of phylloquinone (vitamin K1) and menaquinones (vitamin K2) and total and advanced prostate cancer”
“During a mean follow-up time of 8.6 years, 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 intake [multivariate relative risk (highest compared with lowest quartile): 0.65 ...
“The association was stronger for advanced prostate cancer (0.37 …).
“Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat.”
“Phylloquinone intake was unrelated to prostate cancer incidence”
Note: “The subgroups of menaquinones differed with respect to food sources. Whereas the main food source of MK-4 (median intake 14.4 μg/d) was meat or meat products (37% of total intake), higher menaquinones MK-5–9 (median intake: 18.0 μg/d) were almost exclusively (85% of total intake) derived from dairy products.”
i.e. for PCa protection MK-7 is the significant component.
[2b] (2009 – Germany)
Vitamin K has a role in carboxylation. Of interest in this study was osteocalcin. With adequate vitamin K, osteocalcin becomes carboxylated & calcium can be transported to bone. When osteocalcin is undercarboxylated, calcium is deposited on arterial walls.
Hence, serum undercarboxylated osteocalcin (ucOC) is a biomarker of poor vitamin K intake. The test they used was actually, ucOC / intact total osteocalcin (iOC).
As expected: “Serum ucOC/iOC ratio was positively associated with advanced-stage (OR per 0.1 increment, 1.38 …) and high-grade prostate cancer (OR, 1.21 …) but not with total prostate cancer.”
This is quite important, I feel. The significance of vitamin K appears in advanced-stage PCa rates.
[2c] (2010 – Germany) (broader scope than just PCa)
“During a median follow-up time of >10 years, 1,755 incident cancer cases occurred, of which 458 were fatal. Dietary intake of menaquinones was nonsignificantly inversely associated with overall cancer incidence (HR for the highest compared with the lowest quartile: 0.86 …),
“and the association was stronger for cancer mortality (HR: 0.72 …).
“Cancer risk reduction with increasing intake of menaquinones was more pronounced in men than in women, mainly driven by significant inverse associations with prostate … and lung … cancer.
“We found no association with phylloquinone intake.”
[3] Vitamin K3 (menadione, menaphthone)
Vitamin K3 is technically not a vitamin, since it cannot be found in food, but is a provitamin, since the body can convert it to vitamin K2.
“In the United States, menadione supplements are banned by the U.S. Food and Drug Administration because of their potential toxicity in human use.” [3a]
Vitamin K3 has been explored, in combination with vitamin C (1:100 ratio), in PCa & other studies. Along the way, the combination was patented & given a name: Apatone.
The FDA site lists Apatone as an orphan drug approved for “Treatment of metastatic or locally advanced inoperable transitional cell carcinoma of the urothelium (stage III and IV bladder cancer)”.
There are only two components: sodium ascorbate & menadione sodium bisulfite.
I haven’t been able to find a good account of the product, but it is described as “a combination of vitamin C and vitamin K3 liquid crystals”
“Most anti-tumor drugs target dividing cells; Apatone targets inflammation,” said James Jamison, Ph.D., director of Summa’s Apatone Research Center and the research scientist leading the development of the compound. The nature of Apatone mimics a naturally occurring sugar, allowing Apatone to penetrate cells and interact with ease.” [3b]
“The late Henryk Taper, Ph.D., a researcher at the Catholic University of Leuven in Brussels, Belgium, began research on the role of reactivation of nucleuses in cancer remission in 1967, which led to the description of the vitamin C and K3 combination as an antitumor agent in his doctoral dissertation in 1975.
“Over the course of nearly 20 years, Jamison, in partnership with Taper and Summa researchers Jack Summers, M.D., Ph.D., former chair of the department of urology, now retired; and Jacques Gilloteaux, D.Sc., now a professor of anatomy and cell biology at St. George’s University School of Medicine, United Kingdom, continued to develop the vitamin combination until it became known as Apatone in 2005. ”
““It primes tumor cells to be killed by chemotherapy and radiation,” Jamison said.
“The basis for this is that Apatone resembles glucose, the primary source of energy for tumor cell activity. Rapidly dividing tumor cells rely heavily on glucose for fuel and are full of channels that are fooled into ingesting Apatone.
Once inside cancer cells, Apatone induces oxidative stress, which is a disturbance in the pro-oxidant— antioxidant balance. The process weakens tumor cells, breaking down their defenses and eventually leading to their death. Normal, healthy cells remain intact. The only side effect noted in clinical research has been GERD or gastroesophageal reflux disease.”
It’s odd that there would be any PCa studies, since PCa does not preferentially use glucose for energy.
Odder still is ProsStay, a Jonathan Wright (Life Enhancement) product. It seems to be a blatant rip-off of the patented ratio - & contains K3, which the FDA has supposedly banned for otc use in the U.S. [3c]
[3d] (1996 – U.S. – Jamison & Summers) The first PCa study.
“… increased oxidative stress, subsequent membrane damage, and DNA fragmentation were responsible for enhanced cytotoxicity of the vitamin combination.”
[3e] (2008 – U.S.) Twelve years later(!) – the second PCa study.
“A 12 Week, Open Label, Phase I/IIa Study Using Apatone®”
“At the conclusion of the 12 week treatment period, {PSA velocity} decreased and { PSA doubling time} increased in 13 of 17 patients”
[4] Vitamin K4.
“The goal of this study was to investigate the inhibitory effect of VK4 on human prostate PC-3 cells and the mechanisms involved. We found that VK4 dose-dependently inhibited cell proliferation in PC-3 cells with an IC50 value of about 20.94 microM. Hoechst 33258 Staining results showed that VK4 caused DNA fragmentation in PC-3 cells. PI staining results indicated that VK4-induced PC-3 cell cycle arrest at the S phase. Further mechanistic studies revealed that VK4-mediated induction of apoptosis in PC-3 cell is associated with disruption of mitochondrial membrane potential, down-regulation of Bcl-2, and up-regulation of Bax, release of cytochrome c from mitochondria, and activation of caspase-3 and PARR.”
[5] Vitamin K antagonists [VKA]s. Includes:
•Coumarins: Acenocoumarol.
•Coumatetralyl.
•Dicoumarol.
•Ethyl biscoumacetate.
•Phenprocoumon.
•Warfarin
•1,3-Indandiones: Clorindione.
Diphenadione.
Good news & bad regarding Warfarin, etc. The good news is that in men who are unaware that dysfunctional coagulation is associated with metastasis, the risk is lessened while on Warfarin.
The bad news is that bones become weaker & arteries become calcified. And, we know from the Heidelberg cohort that undercarboxylated osteocalcin increases the risk of advanced PCa.
It’s hard to make sense of the studies. While a man may be on Warfarin long before a PCa diagnosis, a DVT is considered reason to have a PSA test, since the DVT may be due to undiagnosed cancer. For men with PCa, there is increased risk for clotting events & no prophylactic option – except Nattokinase, which is unrecognized by doctors.
[5a] (2011 – Italy)
“Whether long-term use of vitamin K antagonists (VKAs) might affect the incidence of cancer is a longstanding hypothesis. We conducted a population-based study including all cancer- and thromboembolism-free patients of our health area; study groups were defined according to chronic anticoagulant use to VKA-exposed and control groups. Cancer incidence and cancer-related and overall mortality was assessed in both groups. 76,008 patients (3,231 VKA-exposed and 72,777 control subjects) were followed-up for 8.2 (± 3.2) years. After adjusting for age, sex, and time-to-event, the hazard ratio of newly diagnosed cancer in the exposed group was 0.88 ... VKA-exposed patients were less likely to develop prostate cancer, 0.69 ... The adjusted hazard ratio for cancer-related and overall mortality was 1.07 ... and 1.12 .., respectively. These results support the hypothesis that anticoagulation might have a protective effect on cancer development, especially prostate cancer.”
I can’t think of a reasonable explanation why prior VKA use would reduce PCa rates, unless what is happening is that detection rates are being lowered. This would happen if PSA screening isn’t widespread (the population was Italian), since many cases would only be detected when metastatic & VKAs would inhibit metastasis.
[5b] (2013 – Denmark)
“We used data from four Danish nationwide registers. Cases were all Danish individuals with a first-time cancer diagnosis (except nonmelanoma skin cancer) between 2000 and 2009. For each case, eight controls, matched by birth year and gender, were selected from the source population by risk-set sampling.
"Long-term VKA use was defined as exposure to VKA for a period of 3 or more years." Conditional logistic regression was used to compute odds ratios (ORs) for cancer associated with long-term VKA exposure, adjusting for potential confounders."
"A total of 238,196 cases and 1,713,176 controls were included. The adjusted OR for cancer associated with long-term VKA exposure was 0.99 ...
"Long-term VKA use was associated with increased ORs for alcohol- or obesity-related cancer sites, whereas we observed a decreased risk of prostate cancer (OR: 0.86 …).
"Our study does not support a general chemopreventive effect of VKA drugs. However, in accordance with findings from previous studies, we found an inverse association between use of VKA and prostate cancer.”
-Patrick
[1] en.wikipedia.org/wiki/Vitam...
[2a] ajcn.nutrition.org/content/...
[2b] cebp.aacrjournals.org/conte...
[2c] ajcn.nutrition.org/content/...
[3a] en.wikipedia.org/wiki/Menad...
[3b] ic-medtech.com/media/SUMMA_...
[3c] iherb.com/life-enhancement-...
[3d] ncbi.nlm.nih.gov/pubmed/900...
[3e] ncbi.nlm.nih.gov/pmc/articl...
[4] ncbi.nlm.nih.gov/pubmed/238...
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