Updated: August 9, 2007
The Vitamin D3 Debate Continues
Dermatologists and Other Cancer Experts Examine the Data for Clues
Topics Alert No. 186 Updates the Picture
The picture is hardly clear as the skin cancer risks to CLL patients are viewed against the demonstrated health benefits (including the ability to fight cancers and infections) of sun exposure through the action of Vitamin D3. However, medically supervised supplementation with the active form of this vitamin (cholecalciferol) can still be combined with prudent management of sun exposure to provide most of the benefits of this important mainenance drug. Our Alert #186: the Vitamin D3 Debate Continues, brings you up to date on the debate.
Those Aches and Pains
The Effects of a Hidden Deficiency May be Wrongly Blamed on CLL
Topics Alert No. 47 Identifies an Available Fix for What Possibly Ails You
One of the common mistakes we (and our doctors!) make is attributing everything that goes wrong to CLL — things such as muscle pains and the aches in our bones. You could be suffering from something that can be very easily corrected, a real cheap fix. Not only does it not cost a lot, it is not even toxic (isn't that a welcome change from the usual caveats with chemo drugs?), and it might even help you fight the CLL. But don't do this without medical supervision — overdosing is only too easy and can have lethal consequences. What is this drug? It is called vitamin D3. Read Topics Alert Number 47, titled Those Pesky Aches and Pains for some interesting pointers.
Vitamin D3: Essential for Health
Dosages, Cautions and the Need for Monitoring
Effective Supplementation Can Help Fight Cancer
Vitamin D is a very potent regulator of cellular biochemistry. We review the research literature on the value of an adequate intake of Vitamin D3 in maintaining general health and in fighting cancer. The literature indicates that the officially recommended dosage (RDA) of the vitamin is barely enough to avoid deficiency diseases and woefully inadequate to provide the multiple health benefits available from this supplement. However, any aggressive supplementation regimen must be carefully monitored and medically supervised since high dosages can lead to systemic toxicity (hypercalcemia) and even death. Our review article, “Vitamin D3: Essential for Health” explores the benefits, raises the caution flags and explains how to benefit from the vitamin without the risk of sun exposure.
World class Experts Help to Nail Down the Facts
The Vitamin D Council
The Vitamin D Council is a well-organized website with comprehensive information on the topic, presented in a straightforward way that patients can understand. The experts behind this organization have impressive credentials. Please do visit this site and read the material presented to decide for yourself whether Vitamin D3 supplementation should be a part of your regimen. The material on their website can certainly provide you with authoritative background to start a conversation with your own doctor(s).
Vitamin D3 as Therapy
Date: April 29, 2003
by Chaya Venkat
It is a fact of life with CLL that there are a number of dangerous autoimmune diseases that seem to thrive in the same patient population. Autoimmune diabetes (type 1) is one of the more dangerous complications of an immune system gone crazy, attacking the wrong cells and letting the cancer cells live unharmed. In the case of autoimmune diabetes, it is the insulin producing islet beta cells of the pancreas that are attacked and killed. Unlike more garden variety diabetes, this has little to do with being obese, or eating too many sweet things and being a couch potato.
A couple of weeks ago I wrote about the potential value of several new Vitamin D3 analogues as possible drugs in treatment of cancers of all types, including CLL. Below is an interesting report on a slightly different use, Vitamin D3 analogues as possible treatment for autoimmune diabetes. Please allow me to sound the same cautionary note here as I did in the previous article on Vitamin D3: it is the most toxic of all the vitamins if ingested at greater than required levels. One of the side effects of Vitamin D toxicity is hypercalcemia, which can be potentially fatal. The moral of the story is that Vitamin D3 therapy is not, repeat, not your average do-it-yourself therapy. Having said that, it is encouraging that scientists are now coming up with many different synthetic versions of Vitamin D3 that appear to have many of the desired qualities, with fewer of the toxic side effects.
These are developments worth watching.
26/04/2002 11:19:53 Europe/Roma
Vitamin D3 Analogue Arrests the Development of Autoimmune Diabetes
Milano, Italy, April 26, 2002 - BioXell SpA announced today the publication of a study in the May issue of the journal Diabetes describing the ability of a synthetic analogue of the active form of vitamin D3 (1,25-dihydroxyvitamin D3) to arrest the development of autoimmune diabetes (type 1 diabetes) in non-obese diabetic (NOD) mice. This study is the first to demonstrate the ability of a selected vitamin D3 analogue to block ongoing diabetes in the adult NOD mouse, a model that closely resembles the pathogenesis of human type 1 diabetes.
"The demonstration that ongoing autoimmune diabetes can be arrested by a relatively short treatment of a vitamin D3 analogue in adult NOD mice suggests that a similar treatment may also inhibit disease progression in pre-diabetic or newly diagnosed type 1 diabetes patients," said Dr Luciano Adorini, Chief Scientific Officer of BioXell and director of the study. "The mechanism of action of this analogue is particularly intriguing because inhibition of disease is associated with an increased frequency of a cell subset in pancreatic lymph nodes, that has recently been demonstrated to have a regulatory role in humans."
The paper, entitled "A 1a,25-Dihydroxyvitamin D3 Analogue Enhances Regulatory T Cells and Arrests Autoimmune Diabetes in NOD Mice," demonstrates that this particular analogue inhibits diabetes development without inducing toxic side effects. There is an unmet clinical need for a safe drug that inhibits disease progression and does not rely on exogenous insulin administration, given the very severe complications associated with this disease. Vitamin D3 analogues have been shown to inhibit autoimmune diseases in several animal models, including autoimmune diabetes, but the compounds tested so far show efficacy in NOD mice with ongoing disease only if combined with strong immunosuppressive agents, like cyclosporine A.
This particularly potent analogue, which embodies 20 years of research, was designed and synthesised by Milan Uskokovic, VP for Chemistry at BioXell Inc., a subsidiary of BioXell located in Nutley, NJ. Dr Uskokovic, a co-author of the paper, developed Rocaltrol, the first Vitamin D3 analogue to enter the market.
About BioXell BioXell is a private research and development biopharmaceutical company with a competitive edge in immunology developing two strong technology platforms based on the TREM receptor system and Vitamin D3 analogues. From these, BioXell has identified molecules to be developed in secondary hyperparathyroidism, benign prostatic hyperplasia, as well as research programmes in type 1 diabetes, transplantation and psoriasis. In March 2002, BioXell raised Euro22m in a first-round financing from a consortium of three top-tier venture capital firms: MPM Capital, Index Ventures and Life Science Partners. BioXell has a network of academic collaborations, including Washington University, St. Louis and the Universities of Arkansas, Milan, Florence, Modena and Zurich.
For further information, please contact:
Chief Executive Officer
Tel. +39.02.2884 803
Chief Administrative Officer
Tel. +39.02.2884 803
Noonan Russo Presence
Veronica Cefis Sellar
Tel. +44.20.7726 4452
Tel. +44.20.7726 4452
Therapy for CLL
Vitamin D3 analog EB1089
Date: March 17, 2003
by Chaya Venkat
And here is the abstract of the article regarding vitamin D3 analog that Dr. Grever referred to in his paper "In Pursuit of a Complete Remission". The URL to the Vitamin D3 article is given below.
PLENARY PAPER: Blood, 1 April 2003, Vol. 101, No. 7, pp. 2454-2459
The vitamin D3 analog EB1089 induces apoptosis via a p53-independent mechanism involving p38 MAP kinase activation and suppression of ERK activity in B-cell chronic lymphocytic leukemia cells in vitro
Chris Pepper, Alun Thomas, Terry Hoy, Donald Milligan, Paul Bentley, and Chris Fegan
From the Departments of Haematology, Llandough Hospital, Penarth, Vale of Glamorgan; University of Wales College of Medicine, Cardiff; and Birmingham Heartlands Hospital, United Kingdom.
EB1089, a novel vitamin D3 analog, has been shown to have cytotoxic and antiproliferative properties in a variety of malignant cells. However, its potential as a treatment for B-cell chronic lymphocytic leukemia (B-CLL) has not been evaluated. EB1089 induced apoptosis in all of the 102 B-CLL samples tested with a mean LD50 (the concentration of EB1089 required to kill 50% of cells) value (± SD) of 2.1 × 108 M (± 1.4 × 108 M). Furthermore, no significant difference was found in the cytotoxicity of EB1089 in B-CLL samples from previously treated and untreated patients (P = .1637). Induction of apoptosis was associated with a reduction in Bcl-2 and Mcl-1 protein expression, but this was evident only in the apoptotic cells. In contrast, the expression of Bax, p21, and p53 was not altered in the viable or apoptotic cells from either B- or T-lymphocyte lineages. EB1089-induced apoptosis was preceded by activation of p38 mitogen-activated protein (MAP) kinase and suppression of extracellular signal-regulated kinase (ERK) activity, and this was associated with downstream activation of caspase-3. The pancaspase inhibitor (Z-VAD-FMK) and the caspase-9 inhibitor (Z-LEHD-FMK) were able to partially abrogate the apoptotic effects of EB1089 but did not affect the phosphorylation of p38 MAP kinase or the suppression of ERK. The B-CLL cells in the study were shown to highly express vitamin D receptor, but an additional receptor-independent mechanism of cell killing cannot be ruled out at this stage. These findings show that EB1089 is a potent apoptosis-inducing agent in B-CLL cells and may be useful in the treatment of B-CLL patients, particularly those with p53 mutations or drug-resistant disease.
© 2003 by The American Society of Hematology.
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