Editing Vitamin K2

[[Information on nutritional supplements people with ALS have been taking]]

* [https://en.wikipedia.org/wiki/Vitamin_K2 Wikipedia Vitamin K2 page]
* [http://examine.com/supplements/Vitamin+K Examine.com Vitamin K page]


== Effects on ALS ==

Human UBIAD1 localizes to mitochondria and converts vitamin K1 to vitamin K2. Vitamin K2 is best known as a cofactor in blood coagulation, but in bacteria it is a membrane-bound electron carrier. Whether vitamin K2 exerts a similar carrier function in eukaryotic cells is unknown. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson’s disease that affects mitochondrial function. We found that vitamin K2 was necessary and sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed severe mitochondrial defects that were rescued by vitamin K2, and, similar to ubiquinone, vitamin K2 transferred electrons in Drosophila mitochondria, resulting in more efficient adenosine triphosphate (ATP) production. Thus, mitochondrial dysfunction was rescued by vitamin K2 that serves as a mitochondrial electron carrier, helping to maintain normal ATP production.{{#pmid:23910074|lovern2013}}{{#pmid:23847050|wang2013}}

Vitamin K2 is a possible treatment for mitochondrial pathologies such as Parkinson's disease and amyotrophic lateral sclerosis.

K2 may protect from Vitamin D3 toxicity if high amounts of D3 is supplemented.{{#pmid:17145139|masterjohn2007}}

Vitamin K2 may induce mitochondria-mediated apoptosis: ''Here, we identified Bcl-2 antagonist killer 1 (Bak) as a molecular target of VK2-induced apoptosis. VK2 directly interacts with Bak and induces mitochondrial-mediated apoptosis. Although Bak and Bcl-2-associated X protein (Bax), another member of the Bcl-2 family, are generally thought to be functionally redundant, only Bak is necessary and sufficient for VK2-induced cytochrome c (cyt c) release and cell death. Moreover, VK2-2,3 epoxide, an intracellular metabolite of VK2, was shown to covalently bind to the cysteine-166 residue of Bak. Several lines of evidence suggested that the covalent attachment of VK2 is critical for apoptosis induction. Thus this study reveals a specific role for Bak in mitochondria-mediated apoptosis. This study also provides insight into the anticancer effects of VK2 and suggests that Bak may be a potential target of cancer therapy.'' {{#pmid:23229512|karasawa2013}}


== Forms  ==

Only few foods have significant amount of K2. There are several menaquinone forms of Vitamin K2, in supplements common are MK-4 and MK-7. Which menaquinones have effect on ALS is unclear (add info here if found). 
MK-7 has longer activity of those two, and utilization from tablets is about 78 %. 
MK-4 has effect from 1.5 mg upwards. MK-4 is short lived and to maximize effect should be used 3 times a day.

== Cautions ==
Unsafe with at least following medical conditions: diabetes, kidney disease, liver disease. Do not take if using warfarin (Coumadin), might decrease warfarin effectiveness. ([http://www.webmd.com/vitamins-supplements/ingredientmono-983-vitamin+k.aspx?activeIngredientId=983&activeIngredientName=vitamin+k&source=1&tabno=6 Source: WebMD])

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== Regulated pathways ==


== Where to get it ==

Humans can partly convert K1 to K2, amount of K1 in a typical diet is 10 times that of vitamin K2. Conversion process is inefficient. K2 is also produced in the large intestine by gut bacteria. Broad-spectrum antibiotics may contribute to K2 deficiency. Animal sources include high-fat dairy products from grass-fed cows, liver, other organs, egg yolks. Animal foods contain MK-4, fermented foods like sauerkraut, natto and miso contain more of the longer subtypes, MK-5 to MK-14.

* Amazon.co.uk - Life Extension Super K with Advanced K2 Complex x90 Softgels
* iHerb.com - Life Extension Super K with Advanced K2 Complex x90 Softgels

== References ==


[http://www.sciencemag.org/content/336/6086/1241.summary Vitamin K2 Takes Charge]

Science 8 June 2012:
Vol. 336 no. 6086 pp. 1241-1242
DOI: 10.1126/science.1223812

Sheetal Bhalarao, Thomas R. Clandinin

Mitochondria are dynamic organelles that play central roles in eukaryotic cellular energy metabolism. They harbor an electron transport chain (ETC) that couples electron transfer to the movement of protons across the mitochondrial inner membrane, forming an electrochemical gradient that captures chemical energy in the form of adenosine triphosphate (ATP). The biochemical and biophysical properties of the ETC have been studied in detail (1). On page 1306 of this issue, Vos et al. (2) report a new constituent of this chain. The authors show that vitamin K2 is an electron carrier, suggesting this small organic molecule as a possible treatment for mitochondrial pathologies such as Parkinson's disease and amyotrophic lateral sclerosis.


[http://www.sciencemag.org/content/336/6086/1306.abstract Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency]

Published Online May 10 2012 Science 8 June 2012:
Vol. 336 no. 6086 pp. 1306-1310
DOI: 10.1126/science.1218632

Melissa Vos, Giovanni Esposito, Janaka N. Edirisinghe, Sven Vilain, Dominik M. Haddad, Jan R. Slabbaert, Stefanie Van Meensel, Onno Schaap, Bart De Strooper, R. Meganathan, Vanessa A. Morais, Patrik Verstreken

Human UBIAD1 localizes to mitochondria and converts vitamin K1 to vitamin K2. Vitamin K2 is best known as a cofactor in blood coagulation, but in bacteria it is a membrane-bound electron carrier. Whether vitamin K2 exerts a similar carrier function in eukaryotic cells is unknown. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson’s disease that affects mitochondrial function. We found that vitamin K2 was necessary and sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed severe mitochondrial defects that were rescued by vitamin K2, and, similar to ubiquinone, vitamin K2 transferred electrons in Drosophila mitochondria, resulting in more efficient adenosine triphosphate (ATP) production. Thus, mitochondrial dysfunction was rescued by vitamin K2 that serves as a mitochondrial electron carrier, helping to maintain normal ATP production.


[http://neurosciencenews.com/als-parkinsons-pink1-2424/ New Potential Pathway for Treating ALS and Parkinson’s Diseases]

Neuroscience News August 12, 2015
Mutations in PINK1 and its partner molecule Parkin cause hereditary forms of Parkinson’s disease. Moreover, the inability to remove defective mitochondria from nerve cells has been linked to numerous neurodegenerative diseases, including the more common forms of Parkinson’s disease and amyotrophic lateral sclerosis (ALS).


[http://www.ncbi.nlm.nih.gov/pubmed/24128678 Altered expression of DJ-1 and PINK1 in sporadic ALS and in the SOD1(G93A) ALS mouse model.]

Mitochondrial dysfunction is an important mechanism in the pathogenesis of neurodegenerative diseases such as Parkinson disease and amyotrophic lateral sclerosis (ALS). DJ-1 and PTEN-induced putative kinase 1 (PINK1) are important proteins for the maintenance of mitochondrial function and protection against cell death. Mutations in the genes coding for these proteins cause familial forms of Parkinson disease. Recent studies have postulated that changes in the expression of both proteins are also involved in pathologic mechanisms in ALS mouse models. Here, we studied the mRNA and protein expression of PINK1 and DJ-1 in postmortem brain and spinal cord tissue and muscle biopsy samples from ALS patients and controls and in brain, spinal cord, and gastrocnemius muscle of SOD1(G93A) ALS mice at different disease stages. We found significant decreases of PINK1 and DJ-1 mRNA levels in muscle tissue of SOD1(G93A) mice. Together with the significant decrease of PINK1 mRNA levels in human ALS muscle tissue, statistically nonsignificant reduction of DJ-1 mRNA levels, and reduced immunostaining for PINK1 in human ALS muscle, the results suggest potential pathophysiologic roles for these proteins in both mutant SOD1 transgenic mice and in sporadic ALS(G93A).
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	Mitochondrial dysfunction is an important mechanism in the pathogenesis of neurodegenerative diseases such as Parkinson disease and amyotrophic lateral sclerosis (ALS). DJ-1 and PTEN-induced putative kinase 1 (PINK1) are important proteins for the maintenance of mitochondrial function and protection against cell death. Mutations in the genes coding for these proteins cause familial forms of Parkinson disease. Recent studies have postulated that changes in the expression of both proteins are also involved in pathologic mechanisms in ALS mouse models. Here, we studied the mRNA and protein expression of PINK1 and DJ-1 in postmortem brain and spinal cord tissue and muscle biopsy samples from ALS patients and controls and in brain, spinal cord, and gastrocnemius muscle of SOD1(G93A) ALS mice at different disease stages. We found significant decreases of PINK1 and DJ-1 mRNA levels in muscle tissue of SOD1(G93A) mice. Together with the significant decrease of PINK1 mRNA levels in human ALS muscle tissue, statistically nonsignificant reduction of DJ-1 mRNA levels, and reduced immunostaining for PINK1 in human ALS muscle, the results suggest potential pathophysiologic roles for these proteins in both mutant SOD1 transgenic mice and in sporadic ALS(G93A).		Mitochondrial dysfunction is an important mechanism in the pathogenesis of neurodegenerative diseases such as Parkinson disease and amyotrophic lateral sclerosis (ALS). DJ-1 and PTEN-induced putative kinase 1 (PINK1) are important proteins for the maintenance of mitochondrial function and protection against cell death. Mutations in the genes coding for these proteins cause familial forms of Parkinson disease. Recent studies have postulated that changes in the expression of both proteins are also involved in pathologic mechanisms in ALS mouse models. Here, we studied the mRNA and protein expression of PINK1 and DJ-1 in postmortem brain and spinal cord tissue and muscle biopsy samples from ALS patients and controls and in brain, spinal cord, and gastrocnemius muscle of SOD1(G93A) ALS mice at different disease stages. We found significant decreases of PINK1 and DJ-1 mRNA levels in muscle tissue of SOD1(G93A) mice. Together with the significant decrease of PINK1 mRNA levels in human ALS muscle tissue, statistically nonsignificant reduction of DJ-1 mRNA levels, and reduced immunostaining for PINK1 in human ALS muscle, the results suggest potential pathophysiologic roles for these proteins in both mutant SOD1 transgenic mice and in sporadic ALS(G93A).
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