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[[Information on nutritional supplements people with ALS have been taking]] | [[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 == | == 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. | + | 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. |
Vitamin K2 is a possible treatment for mitochondrial pathologies such as Parkinson's disease and amyotrophic lateral sclerosis. | 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. | + | K2 may protect from Vitamin D3 toxicity if high amounts of D3 is supplemented. |
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== Forms == | == Forms == | ||
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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. | 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. | ||
− | == | + | == Discussion threads on the ALSTDI forum == |
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+ | [http://www.alstdi.org/forum/yaf_postst50814_immune-modulation-in-als--harmful-or-beneficial.aspx Immune modulation in ALS - harmful or beneficial?] | ||
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== Regulated pathways == | == Regulated pathways == | ||
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== References == | == References == | ||
+ | [1] | ||
+ | <bibtex> | ||
+ | @article{Masterjohn2007, | ||
+ | abstract = {The dose of vitamin D that some researchers recommend as optimally therapeutic exceeds that officially recognized as safe by a factor of two; it is therefore important to determine the precise mechanism by which excessive doses of vitamin D exert toxicity so that physicians and other health care practitioners may understand how to use optimally therapeutic doses of this vitamin without the risk of adverse effects. Although the toxicity of vitamin D has conventionally been attributed to its induction of hypercalcemia, animal studies show that the toxic endpoints observed in response to hypervitaminosis D such as anorexia, lethargy, growth retardation, bone resorption, soft tissue calcification, and death can be dissociated from the hypercalcemia that usually accompanies them, demanding that an alternative explanation for the mechanism of vitamin D toxicity be developed. The hypothesis presented in this paper proposes the novel understanding that vitamin D exerts toxicity by inducing a deficiency of vitamin K. According to this model, vitamin D increases the expression of proteins whose activation depends on vitamin K-mediated carboxylation; as the demand for carboxylation increases, the pool of vitamin K is depleted. Since vitamin K is essential to the nervous system and plays important roles in protecting against bone loss and calcification of the peripheral soft tissues, its deficiency results in the symptoms associated with hypervitaminosis D. This hypothesis is circumstantially supported by the observation that animals deficient in vitamin K or vitamin K-dependent proteins exhibit remarkable similarities to animals fed toxic doses of vitamin D, and the observation that vitamin D and the vitamin K-inhibitor Warfarin have similar toxicity profiles and exert toxicity synergistically when combined. The hypothesis further proposes that vitamin A protects against the toxicity of vitamin D by decreasing the expression of vitamin K-dependent proteins and thereby exerting a vitamin K-sparing effect. If animal experiments can confirm this hypothesis, the models by which the maximum safe dose is determined would need to be revised. Physicians and other health care practitioners would be able to treat patients with doses of vitamin D that possess greater therapeutic value than those currently being used while avoiding the risk of adverse effects by administering vitamin D together with vitamins A and K.}, | ||
+ | author = {Masterjohn, Christopher}, | ||
+ | doi = {10.1016/j.mehy.2006.09.051}, | ||
+ | issn = {0306-9877}, | ||
+ | journal = {Medical hypotheses}, | ||
+ | keywords = {Animals,Humans,Models, Biological,Vitamin A,Vitamin A: metabolism,Vitamin D,Vitamin D: toxicity,Vitamin K Deficiency}, | ||
+ | mendeley-groups = {kvitamin}, | ||
+ | month = jan, | ||
+ | number = {5}, | ||
+ | pages = {1026--34}, | ||
+ | pmid = {17145139}, | ||
+ | title = {{Vitamin D toxicity redefined: vitamin K and the molecular mechanism.}}, | ||
+ | url = {http://www.ncbi.nlm.nih.gov/pubmed/17145139}, | ||
+ | volume = {68}, | ||
+ | year = {2007} | ||
+ | } | ||
+ | </bibtex> | ||
[http://www.sciencemag.org/content/336/6086/1241.summary Vitamin K2 Takes Charge] | [http://www.sciencemag.org/content/336/6086/1241.summary Vitamin K2 Takes Charge] | ||
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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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