Database Query Results : Vitamin K2, , Risk

VitK2, Vitamin K2: Click to Expand ⟱
Features:
Vitamin K2 (menaquinone)
Menaquinone-4 (MK-4), a subtype of vitamin K2 Helps blood clot, calcium metabolise and heart health.
Bone health: Vitamin K2 helps to regulate calcium levels in the body, which can help to prevent conditions such as osteoporosis and fractures.
Vitamin K2 has been studied for its potential role in cancer prevention and treatment. Some of the key findings include:
-Shown to inhibit the growth of cancer cells, including those found in leukemia, lung cancer, and prostate cancer.
-Shown to induce apoptosis (cell death) in cancer cells, which can help to prevent the spread of cancer.
-Shown to have anti-angiogenic effects, which means it can help to prevent the formation of new blood vessels that feed cancer cells.
-Synergistic effects with other nutrients, such as vitamin D and calcium, to enhance its anti-cancer effects.

UBIAD1 is the enzyme that makes MK-4 inside tissues

Vitamin K2 exists in several forms known as menaquinones, with MK-4 and MK-7 being the most studied. MK-4 is often used in Japan for therapeutic purposes, whereas MK-7 (derived from bacterial fermentation) is widely available as a supplement in Western countries.
For bone and cardiovascular health—and by extension, exploring potential anticancer benefits—doses for MK-7 commonly range from 90 to 200 micrograms per day.
Risk, Risk: Click to Expand ⟱
Source:
Type:
Risk: by definition reduces risk of disease or cancer.
Down Target direction of risk indicates lower cancer risk.
ChemoPreventive also mean lower cancer risk. But for Chemopreventive an up arrow indicates more preventive. 
Cancer Risk Impact Score (CRIS)
CRIS scale:
–5 = very strong risk reduction
–4 = strong risk reduction
–3 = moderate risk reduction
–2 = modest risk reduction
–1 = weak / context-dependent
0 = neutral




CRIS Exposure / Compound Evidence Cancers Notes




-5 Exercise (overall)
VStrong Hum BC, CRC, Endo, PCa, Liv






-5 Aerobic + resistance VStrong Hum Broad inc + mort






-4 Aerobic exercise (mod–vig) VStrong Hum BC, CRC, Endo






-4 Resistance training (alone) Strong Hum BC, CRC






-3 High-intensity interval training Mod–Strong Hum BC, CRC






-2 NEAT / low-intensity activity Moderate Hum CRC






-5 Cruciferous vegetable pattern Strong Hum Lung, CRC, BC, PCa






-5 Sunlight exposure (physiologic) Strong Hum CRC, BC, PCa






-4 Fasting (metabolic pattern)
Strong Mech + Hum BC, CRC, PCa 






-4 Curcumin
Hum + Pre GI, BC, PCa






-4 Sulforaphane
Hum + Pre Lung, CRC, BC






-4 PEITC
Hum + Pre Lung, CRC, PCa






-4 EGCG (tea matrix)
Strong Hum GI, PCa, BC






-4 Lycopene
Strong Hum PCa






-4 Apigenin
Pre + Diet Hum BC, PCa, CRC 






-4 Luteolin
Pre + Diet Hum Lung, CRC, BC 






-4 Kaempferol
Diet Hum Ov, Panc, Lung






-4 Fisetin
Pre + Early Hum CRC, PCa, Mel






-4 Ellagic acid → Urolithin A
Hum (microbiome) CRC, PCa, BC






-3 Omega-3 (EPA/DHA)
Strong Hum CRC, BC






-3 Vitamin D3 (supp)
Obs + RCT CRC, BC






-3 Garlic (allicin)
Mod Hum GI






-3 Mushroom beta-glucans
Hum adjunct GI, BC






-3 Melatonin
Hum + Mech BC, PCa






-3 Coffee (whole)
Strong Hum Liv, Endo






-2 Quercetin
Limited Hum Lung, CRC






-2 Resveratrol
Limited Hum CRC, BC






-2 I3C / DIM
Mod Hum BC, Cerv






-2 Thymoquinone
Early Hum BC, CRC






-2 Beta-carotene (food)
Hum Lung






-1 Vitamin K2 (MK-4/7)
Limited Hum Liv, PCa






-1 Boron
Obs PCa, Lung






0 Vitamin C (oral)
Strong Hum —






0 Genistein (soy)
Strong Hum BC, PCa






0 Selenium (diet)
Mixed Hum PCa






0 Capsaicin
Mixed Gastric






+2 Vitamin E (alpha only)
Strong RCT PCa






+2 Green tea extract (high-dose)
Case reports Liv






+4 Beta-carotene (supplement)
Strong RCT Lung (smokers)






+5 Alcohol (ethanol)
Strong Hum BC, Liv, Eso







Evidence
Hum        human data
VStrong    very strong
Strong     strong
Mod        moderate
Obs        observational
Pre        preclinical
RCT        randomized controlled trial
Mech       mechanistic
Adjunct    adjunct clinical use


Scientific Papers found: Click to Expand⟱
4770- CoQ10,  VitK2,    Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer
- in-vitro, BC, MDA-MB-231
other↑, CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC
*antiOx↑, CoQ10 (or ubiquinone) is a potent lipid-soluble antioxidant enriched not only in mitochondria but also in plasma membranes
Risk↓, Loss of the CoQ10-biosynthetic enzyme UBIAD1 is associated to a worse prognosis in BC patients.
other↑, Deletion of Ubiad1 gene accelerates BC development in mouse models.
TumMeta↓, UBIAD1 expression limits metastasis formation in aggressive BC lines
ECM/TCF↓, CoQ10 and UBIAD1 expression impairs ECM-mediated signaling and AKT2 pathway in BC cells
Akt2↓,
Ferroptosis↑, UBIAD1 and CoQ10 enhance BC sensitivity to ferroptosis inducers via FSP1
eff↑, While CoQ10 treatment alone does not affect MDA-MB-231 cell viability, the co-treatment with RSL3 significantly enhanced cell death

2285- VitK2,    New insights into vitamin K biology with relevance to cancer
- Review, Var, NA
Risk↓, Vitamin K intake has been inversely associated with cancer incidence and mortality in observational studies
AntiCan↑, MK4 supplementation on bone loss in women with viral liver cirrhosis.Over 8 years of follow-up, the risk ratio for the development of HCC in the MK4 group compared with the control group was 0.20
eff↑, phase 2 randomized placebo-controlled trial in HCC patients demonstrated that MK4 supplementation (45 mg/day orally) enhanced the efficacy of the multi-kinase inhibitor sorafenib
MMP↓, MK4 mediated apoptosis may also involve binding of MK4 to pro-apoptotic BAK, direct effects on mitochondrial membrane depolarization and reactive oxygen species (ROS)
ROS↑,
Cyt‑c↑, MK4 covalently bound to BAK induces decrease in MMP and cytochrome c release.
eff↓, ROS production can be blocked by N-acetyl-cysteine (NAC) and alpha-tocopherol which can ultimately block MK4 mediated apoptosis.
SXR↑, Activation of SXR by MK4 (The loss of UBIAD1 in prostate cancer cells reduced MK4 synthesis which in turn decreased SXR transcriptional regulation)

4309- VitK2,    Vitamins in the Prevention and Support Therapy of Neurodegenerative Diseases
- Review, NA, NA
*Apoptosis↓, vitamin K2 in preventing apoptosis, oxidative stress,
*ROS↓,
*antiOx↑, vitamin K possesses antioxidant properties
*cognitive↑, Some studies suggest that individuals with higher levels of vitamin K exhibit better cognitive function and memory performance
*memory↑,
*Risk↓, brain samples showed that the increased level of vitamin K2 correlated with the reduced risk of dementia, improved cognitive abilities, lower severity of AD, and lower level of phosphorylated Tau protein aggregation
*p‑tau↓,

1818- VitK2,    New insights on vitamin K biology with relevance to cancer
- Review, Var, NA
TumCG↓, A few small randomized trials support the concept that vitamin K supplementation can retard cancer development and/or progression
ChemoSen↑, phase 2 randomized placebo-controlled trial in HCC patients demonstrated that MK4 supplementation (45 mg/day orally) enhanced the efficacy of the multi-kinase inhibitor sorafenib
toxicity∅, long term vitamin K supplementation is safe and may offer survival benefit in HCC patients.
OS↑,
BMD↑, Primary Outcomes: Bone density
eff↑, In studies where both forms of the vitamin have been compared, MKs generally exerted more potent anticancer effects than PK.
MMP↓, direct effects on mitochondrial membrane depolarization and reactive oxygen species (ROS)
ROS↑,
eff↓, ROS neutralization by antioxidants (N-acetyl cysteine (NAC) and alpha-tocopherol) or BAK knockdown prevented MK4 mediated mitochondrial disruption and apoptosis
ERK↑, activates ERK, JNK/p38 MAPK
JNK↑,
p38↑,
Cyt‑c↑, cytochrome c release
Casp↑, caspase activation
ATP↓, reducing ATP production and increasing lactate production
lactateProd↑,
AMPK↑, which activates AMPK
Rho↓, via inhibition of RhoA
TumCG↓, mouse xenograft studies, treatment with MK4 administered in water at a calculated dose of 20 mg/kg/d significantly reduced growth of established HCCs
BioAv↑, Phylloquinone (K1) is the major dietary form, but it is converted into menaquinone (K2) in tissues.
cardioP↑, optimal vitamin K status is common in adults and may contribute to chronic diseases such as osteoporosis, type 2 diabetes and cardiovascular disease.
Risk↓, Observational studies suggest that low vitamin K intake increases cancer risk(more lowers risk)

1824- VitK2,    Vitamin K and its analogs: Potential avenues for prostate cancer management
- Review, Pca, NA
AntiCan↑, potential anticancer activity in several cancer types including prostate cancer
toxicity∅, VK1 and VK2 are non-toxic even at high doses
Risk↓, Epidemiological studies suggest that there is inverse association between dietary intake of VK (especially menaquinone) and overall cancer incidence
Apoptosis↑, VK2 has anticancer activity through the mechanisms such as induction of apoptosis, production of reactive oxygen species (ROS) and cell cycle arrest
ROS↑,
TumCCA↑,
eff↑, Gilloteaux et al. [90] reported that the combination of VK3 and ascorbic acid induces oxidative stress in DU-145 PCa cells.
DNAdam↑, oxidative stress induce lipid and protein oxidative modifications and DNA damage leading to apoptotic cell death
MMP↓, VK2 induces pro-apoptosis effects by regulating the MMP, in which mechanism VK2 produces superoxide within the mitochondrial membrane, followed by the release cytochrome c, activation of procaspase 3
Cyt‑c↑,
pro‑Casp3↑,
FasL↑, VK3 treatment induced c-myc and also increased both FasL and Fas
Fas↑,
TumAuto↑, VK2 also can induce autophagy
ChemoSen↑, combination of vitamins C and VK3 has been proposed as a non-toxic mixture of drugs active as an adjuvant cancer therapy by increasing chemo- or radiotherapy effects through alteration of deoxyribonuclease activity
RadioS↑,

1825- VitK2,    Vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial
- Analysis, Pca, NA
Risk∅, The present study does not suggest that vitamin K intake influences the occurrence of total and advanced prostate cancer in the general US population

1830- VitK2,    Vitamin K Intake and Risk of Lung Cancer: The Japan Collaborative Cohort Study
- Study, Lung, NA
Risk↓, Vitamin K consumption reduces the risk of lung cancer.
NF-kB↓, Vitamin K2 has been shown to suppress nuclear factor (NF)-κB activation via inhibiting protein kinase C (PKC)- α and ε kinase activities
PKCδ↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 3,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   lactateProd↑, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   Casp↑, 1,   pro‑Casp3↑, 1,   Cyt‑c↑, 3,   Fas↑, 1,   FasL↑, 1,   Ferroptosis↑, 1,   JNK↑, 1,   p38↑, 1,  

Transcription & Epigenetics ⓘ

other↑, 2,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,   TumCG↓, 2,  

Migration ⓘ

Akt2↓, 1,   PKCδ↓, 1,   Rho↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

ECM/TCF↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

SXR↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 2,   eff↓, 2,   eff↑, 4,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

BMD↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   cardioP↑, 1,   OS↑, 1,   Risk↓, 5,   Risk∅, 1,   toxicity∅, 2,  
Total Targets: 40

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   ROS↓, 1,  

Cell Death ⓘ

Apoptosis↓, 1,  

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,   memory↑, 1,   Risk↓, 1,  
Total Targets: 7

Scientific Paper Hit Count for: Risk, Risk
7 Vitamin K2
1 Coenzyme Q10
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:168  Target#:785  State#:%  Dir#:%
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