Vitamin D: A Pharmaceutical Fountain - with Hector DeLuca
Vimeo, 60 minute talk, 29 minute Q&A
Renowned biochemist and Wisconsin Academy Fellow Hector DeLuca discusses the profound application of vitamin D in medicine, including new treatments in the areas of immunity and autoimmunity, in this special Wisconsin Academy Talk.
DeLuca shares insight from a career devoted to the research of vitamin D and physiological events linked to the function of this vitamin. Among the most important research activities in his laboratory has been the synthesis of tissue-specific analogs of vitamin D for the treatment of diseases. DeLuca's group has produced eight pharmaceuticals that are used for the treatment of diseases, including osteoporosis, vitamin D-resistant rickets, and bone diseases linked to kidney failure.
Presented by the Wisconsin Academy of Sciences, Arts & Letters, this talk was recorded on May 12, 2015, at the Madison Museum of Contemporary Art lecture hall.
Notes by Henry Lahore of VitaminDWiki
- Doctors became aware of injectable cacitriol causing Calcium problems – 1980’s
- Similar Calcification for the vitamin D analogs
- One of the benefits of injectable vitamin D products is that injectables do not have a first-pass problem with Calcium (not go through gut)
(Comment – this would also be true for sublingual and topical)
- Latest analog vitamin D affects just arathroid without affecting Calcium – should be ready for market in ~ 2 years
- DeLuca says that the entire vitamin D mechanism is gene expression (amplify/catalytic effect)
- Very Very concerned about too much vitamin D – needed for MS, will result in Hypercalcemia – not looking at reducing Ca intake or adding Vitamin K
- Vitamin D prevents MS in rats. Tried putting rats on low Calcium diet ,but then Vitamin D did not treat the MS.
- He came to the conclusion that the hypercalcimia prevented the MS, not the vitamin D itself
- Unable to induce MS (by their technique) in mouse which is vitamin D deficient. ( 54 minutes :48 seconds)
- DeLuca personally takes 4,000 IU, He had recommended 5,000 before Institue of Medicine made their recommendations (2010)
- DeLuca guesses than 50 ng level is optimal – his is at 50 ng
- Bisphosphonate use stops bone repair, resulting in microfractures, etc
- Triennial Growth Symposium--Vitamin D: bones and beyond March 2014 – free full text online
- Minireview: Vitamin D: is there a role in extraskeletal health? Aug 2011
- A Half-century of Vitamin D: the Work of Hector F. DeLuca full text
December 2006 The Journal of Biological Chemistry, 281, e41.
- History of the discovery of vitamin D and its active metabolites 2014 full text
- Hector F DeLuca Emeritus Professor 2011-present - his webpage
Molecular function of vitamins and hormones, metabolism of vitamins A and D (June 2015)
Professor H. F. DeLuca's laboratory has been devoted to the understanding of metabolism and mechanism of action of vitamins A and D. Initially, work in this group centered around describing which forms of vitamin D and vitamin A are active in correcting deficiency disease. In particular, in the 1960's by means of isolation, chemical identification and chemical synthesis, this laboratory demonstrated that vitamin D itself is biologically inactive and must be modified by sequential action by the liver and kidney to prepare the hormone derived from vitamin D, namely 1,25-dihydroxyvitamin D3. Not only the hormonal form but many of its analogs were chemically synthesized in this research group and developed for the treatment of a variety of diseases including osteoporosis, vitamin D dependency rickets, and bone disease of kidney failure. More recently, this laboratory has devoted its efforts to understanding how 1,25-dihydroxyvitamin D3 functions in the target tissues. A receptor which recognizes this hormone has been identified in target tissue nuclei. It has been cloned and its entire amino acid and nucleotide coding sequence has been determined. We have successfully expressed it in large quantities in baculovirus and bacteria and are in the process of crystallizing the protein for three-dimensional structural work. Response elements or specific DNA sequences to which the receptor binds in order to initiate transcription of the genes have also been identified. Other molecular biology techniques are being applied to isolate genes and identify the proteins that are made in response to 1,25-dihydroxyvitamin D3. By locating the receptor in tissues not previously recognized as targets of vitamin D action, new functions for vitamin D have been identified. It is now clear that 1,25-(OH)2D3 serves as a developmental hormone as well as a hormone responsible for regulating calcium and phosphorus. It has also been found to be necessary for reproductive function in females, for the immune system, and for the development of giant osteoclasts responsible for remodeling bone. Our laboratory uses a combination of molecular biology techniques, organic chemical techniques, physiological techniques, and cell biology techniques to learn the molecular mechanism of action of these fat-soluble substances. There is considerable effort dedicated to collaboration with the medical world for the application of the newly synthesized analogs of the vitamin D compounds and of vitamin A compounds for the treatment of disease. The most recent application has been to prevent and arrest such autoimmune diseases as multiple sclerosis and rheumatoid arthritis, and as an anti-transplant rejection drug.