annoyingly this study did not show reversal like the others, just a slowing of calcification like a lot of the studies do Effect of vitamin K1 supplementation on matrix Gla protein level and vascular calcification in hemodialysis patients - The Egyptian Journal of Internal Medicine
10mg 3x a week did not reverse calcification (same dose used in the 2nd case report)
their MGP did not go up a lot. which tells me they didn't uncarboxylate a significant enough % of the elevated MGP to see calcification reversal, it slowed
studies that don't work with K1 / K2 or only show slowing of calcification instead of reversing, show only up to 40% reduction of uncarboxylated MGP. which suggests you need to reduce most or all of it for the reversal effect. and total levels are elevated 2x - 3x in people with calciphylaxis so more K is needed to get the full carboxylation of elevated MGP
but the megadose in the first study should have been enough
is retinol the missing factor?
studies are mixed on whether it increases total or decreases total MGP. which would give more or less MGP needed to carboxylate & so more or less K needed for the calcification reversal effect.
Potent Inhibition of Heterotopic Ossification by Nuclear Retinoic Acid Receptor γ Agonists -> vit A receptor agonists inhibit calcification
Increased dietary intake of vitamin A promotes aortic valve calcification in vivo - PubMed -> but high doses of vitamin A actually have the opposite effect & increase calcification (mice eat ~4g food daily so 100,000iu - 150,000iu daily human equivalent i think? compared to 10,000iu - 15000iu)
chris masterjohn blog post on this with another study
in the 1st case report below her retinol was out of range.
they supplemented her with 3500iu alongside the k1 and calcification reversed for full tissue healing
So if retinol is the extra co-factor this suggests daily 3500iu is enough. too much might give reverse effect
https://academic.oup.com/ckj/article/11/4/528/4616523
This woman had significant calcification of blood vessels causing ulcerations on her calf & leg (Calciphylaxis). regardless of being normocalcaemic in blood tests. Her plasma vitamin K was so low they couldn't even detect it so <0.3 nmol/L (reference range 0.3–2.6). and her plasma vitamin A was 0.8 μmol/L (reference range 1.6–2.3), her parathyroid hormone was 28 pmol/L (reference range <7.5 pmol/L
Her PTH shot up after month 6 as her calcium dropped below a level. but that didn't change the reversal of calcification into month 12, likely because she then had adequate Vit K (& A?). Her wounds healed by month 12. (faster in the other case report)
They also lowered dialysate calcium & increased dialysis during the study. but lowering calcium / increasing dialysis alone wouldn't reverse existing calcification i don't think. so it's the K (+ A maybe). "It seems likely that, of the co-interventions, vitamin K supplementation had the greatest impact on the patient’s recovery."
Vitamin K–Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis
the fraction of total MGP that was carboxylated was lower in cases than in controls. Vitamin K deficiency was more common than in controls.
Plasma levels of both ucMGP (3076±289 pM versus 1485±436, P<0.001) and cMGP (3075±289 pM versus 2688±314 pM, P=0.002) were higher in calciphylaxis cases compared with controls
Similarly, in analyses restricted to patients not taking warfarin, plasma levels of ucMGP (3042±385 pM versus 1099±172 pM, P<0.001) and cMGP (3989±277 pM versus 3024±312 pM, P=0.03) were higher in calciphylaxis cases compared with controls
2mg daily slowed but did not reverse
There's another study in a woman with ulcerated calves from calcification "Successful treatment of calciphylaxis with vitamin K in a patient on haemodialysis" - using 10mg k1 3x a week
maybe her retinol levels were good so she carboxylated a high enough % using the same dose as the first study?
"Two months after starting phylloquinone, her pain and the ulcers had significantly improved and by 3 months they had resolved. Against our advice, she decided to cease phylloquinone. Seven months after her initial presentation (4 months after ceasing phylloquinone), the calciphylaxis recurred (see Supplementary Data). At this time, her plasma vitamin K was 0.7 nmol/L (reference range 0.3–2.6), and her PTH was over 200 pmol/L. She agreed to recommence 10 mg phylloquinone thrice weekly, this time given intravenously. She did not undergo further angioplasty. within 3 months, there was near-complete healing of her ulcers and significant improvement of her pain"
10mg 3x a week did not reverse calcification (same dose used in the 2nd case report)
their MGP did not go up a lot. which tells me they didn't uncarboxylate a significant enough % of the elevated MGP to see calcification reversal, it slowed
studies that don't work with K1 / K2 or only show slowing of calcification instead of reversing, show only up to 40% reduction of uncarboxylated MGP. which suggests you need to reduce most or all of it for the reversal effect. and total levels are elevated 2x - 3x in people with calciphylaxis so more K is needed to get the full carboxylation of elevated MGP
but the megadose in the first study should have been enough
is retinol the missing factor?
studies are mixed on whether it increases total or decreases total MGP. which would give more or less MGP needed to carboxylate & so more or less K needed for the calcification reversal effect.
Potent Inhibition of Heterotopic Ossification by Nuclear Retinoic Acid Receptor γ Agonists -> vit A receptor agonists inhibit calcification
Increased dietary intake of vitamin A promotes aortic valve calcification in vivo - PubMed -> but high doses of vitamin A actually have the opposite effect & increase calcification (mice eat ~4g food daily so 100,000iu - 150,000iu daily human equivalent i think? compared to 10,000iu - 15000iu)
chris masterjohn blog post on this with another study
in the 1st case report below her retinol was out of range.
they supplemented her with 3500iu alongside the k1 and calcification reversed for full tissue healing
So if retinol is the extra co-factor this suggests daily 3500iu is enough. too much might give reverse effect
https://academic.oup.com/ckj/article/11/4/528/4616523
This woman had significant calcification of blood vessels causing ulcerations on her calf & leg (Calciphylaxis). regardless of being normocalcaemic in blood tests. Her plasma vitamin K was so low they couldn't even detect it so <0.3 nmol/L (reference range 0.3–2.6). and her plasma vitamin A was 0.8 μmol/L (reference range 1.6–2.3), her parathyroid hormone was 28 pmol/L (reference range <7.5 pmol/L
Her PTH shot up after month 6 as her calcium dropped below a level. but that didn't change the reversal of calcification into month 12, likely because she then had adequate Vit K (& A?). Her wounds healed by month 12. (faster in the other case report)
They also lowered dialysate calcium & increased dialysis during the study. but lowering calcium / increasing dialysis alone wouldn't reverse existing calcification i don't think. so it's the K (+ A maybe). "It seems likely that, of the co-interventions, vitamin K supplementation had the greatest impact on the patient’s recovery."
Vitamin K–Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis
the fraction of total MGP that was carboxylated was lower in cases than in controls. Vitamin K deficiency was more common than in controls.
Plasma levels of both ucMGP (3076±289 pM versus 1485±436, P<0.001) and cMGP (3075±289 pM versus 2688±314 pM, P=0.002) were higher in calciphylaxis cases compared with controls
Similarly, in analyses restricted to patients not taking warfarin, plasma levels of ucMGP (3042±385 pM versus 1099±172 pM, P<0.001) and cMGP (3989±277 pM versus 3024±312 pM, P=0.03) were higher in calciphylaxis cases compared with controls
2mg daily slowed but did not reverse
There's another study in a woman with ulcerated calves from calcification "Successful treatment of calciphylaxis with vitamin K in a patient on haemodialysis" - using 10mg k1 3x a week
maybe her retinol levels were good so she carboxylated a high enough % using the same dose as the first study?
"Two months after starting phylloquinone, her pain and the ulcers had significantly improved and by 3 months they had resolved. Against our advice, she decided to cease phylloquinone. Seven months after her initial presentation (4 months after ceasing phylloquinone), the calciphylaxis recurred (see Supplementary Data). At this time, her plasma vitamin K was 0.7 nmol/L (reference range 0.3–2.6), and her PTH was over 200 pmol/L. She agreed to recommence 10 mg phylloquinone thrice weekly, this time given intravenously. She did not undergo further angioplasty. within 3 months, there was near-complete healing of her ulcers and significant improvement of her pain"
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