Hi, all.
Will Marsden just sent me this new abstract. I think it adds to the evidence showing the importance of getting the vitamin D level up. This study shows that vitamin D raises the gene expression of the cystathionine beta synthase (CBS) enzyme, which converts homocysteine to cystathionine, and is the gateway into the transsulfuration pathway, which, among other things, makes cysteine, which is needed for the synthesis of glutathione.
Lately I've been seeing test results on several PWCs/PWMEs who have lower than normal flow through the transsulfuration pathway. Low vitamin D may be a contributor to this.
Having the vitamin D level up should help to normalize the glutathione level, based on the results of this study. This is one more piece of information that supports the advisability of getting vitamin D up. As you may know, Dr. John Cannell a few years ago found that giving his patients 5,000 IU per day of vitamin D3 caused all 30 of them not to get the flu when it ran through Atascadero State Hospital in California, where he works. Perhaps this effect on CBS is connected with the protection against flu, because raising glutathione will give better Th1 immune response, which is the type of response needed against viruses. As you may also know, the RDA committee of the Institute of Medicine has recently raised their recommendation for vitamin D intake, but they brought it up only to 600 IU per day. This may not be enough for most people to get them into the optimum range of vitamin D levels. Vitamin D is toxic at very high dosages, perhaps above about 10,000 IU on a steady basis. There does not seem to be good data on the toxic levels so far. Some people take higher than this amount for short times to get their levels up, and this seems to be O.K. It's a good idea to work with your physician and have your vitamin D level measured periodically when supplementing at high dosages. I'm trying to keep my vitamin D level above 50 ng/ml. More information is available on vitamin D at www.vitamindcouncil.org.
Best regards,
Rich
J Bone Miner Res. 2011 Aug 23. doi: 10.1002/jbmr.493. [Epub ahead of print]
1,25-dihydroxyvitamin D(3) influences cellular homocysteine levels in murine pre-osteoblastic MC3T3-E1?cells by direct regulation of cystathionine ?-synthase.
Kriebitzsch C, Verlinden L, Eelen G, van Schoor NM, Swart K, Lips P, Meyer MB, Pike JW, Boonen S, Carlberg C, Vitvitsky V, Bouillon R, Banerjee R, Verstuyf A.
Source
Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Catholic University of Leuven, Gasthuisberg O&N 1, Herestraat 49, B-3000 Leuven, Belgium.
Abstract
High homocysteine (HCY) levels are a risk factor for osteoporotic fracture. Furthermore, bone quality and strength are compromised by elevated HCY due to its negative impact on collagen maturation. HCY is cleared by cystathionine ?-synthase (CBS), the first enzyme in the transsulfuration pathway. CBS converts HCY to cystathionine, thereby committing it to cysteine synthesis. A microarray experiment on MC3T3-E1 murine pre-osteoblasts treated with 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] revealed a cluster of genes including the cbs gene, of which the transcription was rapidly and strongly induced by 1,25(OH)(2) D(3) . Quantitative real-time PCR and Western blot analysis confirmed higher levels of cbs mRNA and protein after 1,25(OH)(2) D(3) treatment in murine and human cells. Moreover, measurement of CBS enzyme activity and quantitative measurements of HCY, cystathionine and cysteine concentrations were consistent with elevated transsulfuration activity in 1,25(OH)(2) D(3) -treated cells. The importance of a functional vitamin D receptor (VDR) for transcriptional regulation of cbs was shown in primary murine VDR knock-out osteoblasts, in which up-regulation of cbs in response to 1,25(OH)(2) D(3) was abolished. Chromatin immunoprecipitation on chip and transfection studies revealed a functional vitamin D response element in the second intron of cbs. To further explore the potential clinical relevance of our ex vivo findings, human data from the Longitudinal Aging Study Amsterdam suggested a correlation between vitamin D status [25(OH)D(3) levels] and HCY levels. In conclusion, this study demonstrated that cbs is a primary 1,25(OH)(2) D(3) target gene which renders HCY metabolism responsive to 1,25(OH)(2) D(3) . 2011 American Society for Bone and Mineral Research.
Copyright 2011 American Society for Bone and Mineral Research.
PMID:
21898591
Will Marsden just sent me this new abstract. I think it adds to the evidence showing the importance of getting the vitamin D level up. This study shows that vitamin D raises the gene expression of the cystathionine beta synthase (CBS) enzyme, which converts homocysteine to cystathionine, and is the gateway into the transsulfuration pathway, which, among other things, makes cysteine, which is needed for the synthesis of glutathione.
Lately I've been seeing test results on several PWCs/PWMEs who have lower than normal flow through the transsulfuration pathway. Low vitamin D may be a contributor to this.
Having the vitamin D level up should help to normalize the glutathione level, based on the results of this study. This is one more piece of information that supports the advisability of getting vitamin D up. As you may know, Dr. John Cannell a few years ago found that giving his patients 5,000 IU per day of vitamin D3 caused all 30 of them not to get the flu when it ran through Atascadero State Hospital in California, where he works. Perhaps this effect on CBS is connected with the protection against flu, because raising glutathione will give better Th1 immune response, which is the type of response needed against viruses. As you may also know, the RDA committee of the Institute of Medicine has recently raised their recommendation for vitamin D intake, but they brought it up only to 600 IU per day. This may not be enough for most people to get them into the optimum range of vitamin D levels. Vitamin D is toxic at very high dosages, perhaps above about 10,000 IU on a steady basis. There does not seem to be good data on the toxic levels so far. Some people take higher than this amount for short times to get their levels up, and this seems to be O.K. It's a good idea to work with your physician and have your vitamin D level measured periodically when supplementing at high dosages. I'm trying to keep my vitamin D level above 50 ng/ml. More information is available on vitamin D at www.vitamindcouncil.org.
Best regards,
Rich
J Bone Miner Res. 2011 Aug 23. doi: 10.1002/jbmr.493. [Epub ahead of print]
1,25-dihydroxyvitamin D(3) influences cellular homocysteine levels in murine pre-osteoblastic MC3T3-E1?cells by direct regulation of cystathionine ?-synthase.
Kriebitzsch C, Verlinden L, Eelen G, van Schoor NM, Swart K, Lips P, Meyer MB, Pike JW, Boonen S, Carlberg C, Vitvitsky V, Bouillon R, Banerjee R, Verstuyf A.
Source
Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Catholic University of Leuven, Gasthuisberg O&N 1, Herestraat 49, B-3000 Leuven, Belgium.
Abstract
High homocysteine (HCY) levels are a risk factor for osteoporotic fracture. Furthermore, bone quality and strength are compromised by elevated HCY due to its negative impact on collagen maturation. HCY is cleared by cystathionine ?-synthase (CBS), the first enzyme in the transsulfuration pathway. CBS converts HCY to cystathionine, thereby committing it to cysteine synthesis. A microarray experiment on MC3T3-E1 murine pre-osteoblasts treated with 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] revealed a cluster of genes including the cbs gene, of which the transcription was rapidly and strongly induced by 1,25(OH)(2) D(3) . Quantitative real-time PCR and Western blot analysis confirmed higher levels of cbs mRNA and protein after 1,25(OH)(2) D(3) treatment in murine and human cells. Moreover, measurement of CBS enzyme activity and quantitative measurements of HCY, cystathionine and cysteine concentrations were consistent with elevated transsulfuration activity in 1,25(OH)(2) D(3) -treated cells. The importance of a functional vitamin D receptor (VDR) for transcriptional regulation of cbs was shown in primary murine VDR knock-out osteoblasts, in which up-regulation of cbs in response to 1,25(OH)(2) D(3) was abolished. Chromatin immunoprecipitation on chip and transfection studies revealed a functional vitamin D response element in the second intron of cbs. To further explore the potential clinical relevance of our ex vivo findings, human data from the Longitudinal Aging Study Amsterdam suggested a correlation between vitamin D status [25(OH)D(3) levels] and HCY levels. In conclusion, this study demonstrated that cbs is a primary 1,25(OH)(2) D(3) target gene which renders HCY metabolism responsive to 1,25(OH)(2) D(3) . 2011 American Society for Bone and Mineral Research.
Copyright 2011 American Society for Bone and Mineral Research.
PMID:
21898591
