Topics Alert

Those Pesky Aches and Pains

Date: October 5, 2024

One of the common mistakes we (and our doctors!) make is attributing everything that goes wrong to CLL. If you are tired, you hurt all over, your muscles ache, heck you can feel the pain in your very bones, and nothing works, not even fistfulls of NSAIDs, why, it must be the dreaded CLL acting up, right?

Not so fast, you could be dead wrong laying this at the door of the 'dragon'. 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. What is this drug? It is called vitamin D3. I have discussed this topic before on Topics (Vitamin D3 Essential for Health) but I think it bears repeating. Below are direct quotes from a very recent paper in the prestigious Mayo Proceedings, December of 2024. You can read the whole article for free, as well as the editorial that accompanied it. I have provided the links below.

There are two reason for my visiting the issue of vitamin D3 deficiency again. First, it is all too easy to dismiss the symptoms of vitamin D3 deficiency, especially when we are dealing with a bunch of cancer patients. Doctors expect us to complain of aches and pains, what else is new? If they take us seriously at all, they may consider something like fibromyalgia, in addition to the catch-all of CLL. Most often, you are expected to grin and bear it, with the not-so-subtle sub-text: stop whining.

The other reason is that I still see "miraculous" claims made for "coral" calcium, with no understanding of calcium homeostasis and how calcium is used in our bodies. Calcium absorption needs adequate vitamin D3, otherwise it just goes for the ride, in one end and out the other. Trust me, your toilet does not need any more calcium. "Coral" calcium is no better than regular calcium you get at the drug store, or even antacids like Tums, it just costs more. It is also significantly worse in one important respect, the presence of high levels of very toxic heavy metals such as mercury. Coral has had a long time to accumulate the heavy metal toxins we have been putting out into the oceans. You worry about eating fish that have lived for a few years, about the level of heavy metals they may have accumulated over that time. Folks, coral has been around a lot longer, and was busy accumulating all the mercury and other heavy metals we were pumping into the oceans in the bad old days, before environmentalism became 'cool'.

Here is what the Mayo Clinic had to say on the subject of vitamin D3, calcium, mysterious aches and pains. They specifically talk about potential misdiagnosis of fibromyalgia, when the problem could well be vitamin D3 deficiency - something that can be easily tested for, and fixed. The quotes are from Mayo, but I did the highlighting to identify points of interest.

• Overall, 93% of the 150 children and adults in the study, which included 6 broad categories of ethnic groups, were vitamin D-deficient. Is this unexpected? No. Is this newsworthy? Yes.
• (The authors) evaluated both children and adults who reported persistent musculoskeletal pain that did not meet the strict criteria for fibromyalgia defined by the American College of Rheumatology. The association between nonspecific musculoskeletal pain and vitamin D deficiency was suspected because of a higher prevalence of these symptoms during winter than summer.
• Vitamin D is essential for the efficient utilization of dietary calcium. In a vitamin D-deficient state, the amount of calcium absorbed is inadequate to satisfy the body's calcium requirement, This results in osteopenia and osteoporosis. This is the likely explanation of why patients with osteomalacia often experience a dull unrelenting aching sensation in their bones. These symptoms are either dismissed or misdiagnosed as fibromyalgia by many physicians.
• Vitamin D deficiency causes muscle weakness and muscle aches and pains in both children and adults.
• It has been estimated that 90% or more of our required vitamin D comes from exposure to sunlight. Anything that interferes with the penetration of solar ultraviolet radiation into the skin, such as increased melanin pigmentation and sunscreen use, will diminish the cutaneous production of vitamin D3.
• People who live at higher latitudes and who are more prone to vitamin D deficiency are at increased risk of developing prostate, colon, breast, and other solid tumors; autoimmune diseases including multiple sclerosis and type 1 diabetes; hypertension; and cardiovascular heart disease.
• When patients with nonspecific skeletomuscular pain are evaluated, their serum 25-hydroxyvitamin D levels should be obtained. Physicians should disregard the laboratory-reported lower limit of the normal range. A serum 25-hydroxyvitamin D level of at least 20 ng/mL is necessary to minimally satisfy the body's vitamin D requirement. Maintenance of a serum 25-hydroxyvitamin D level of 30 to 50 ng/mL is preferred.
• Patients should have their vitamin D status, ie, serum 25-hydroxyvitamin D levels, tested once a year, preferably at the end of the fall season, to ensure that they do not become vitamin D-deficient before winter.

Mayo Proceedings Article

Mayo Proceedings Letters on Vitamin D

I thought you folks might also like to see the two abstracts below. The first one talks about calcitriol (another name for Vitamin D), in clinical trials at Roswell Park Cancer Institute for its anti-cancer activity. The second one talks about a vitamin D3 analog that seems to be effective in CLL. Why the vitamin D3 analog? Why not just use the cheap and available vitamin D3? That is an important question. If you overdose on vitamin D3, it can lead to something very dangerous, called hypercalcemia, which means too much calcium in your blood. Hypercalcemia can be fatal, if it is not immediately detected and treated. The reason for developing the vitamin D3 analog is to see if we can keep the anti-cancer effects, while avoiding the problems with hypercalcemia. Good concept: we need to keep an eye on this initiative, see how far it goes.

In the meantime, please do discuss your vitamin D3 status with your doctor. You may want to revisit our review article "Vitamin D3: Essential for your health" on our website, to get your arms around the arguments you may need to make, to bring your doctor on board. In my opinion, it surely pays to be pro-active on this front. Do remember, unlike the general Joe Shmoe basking on the beach, as CLL patients you have significantly higher (ten times higher!) risk of skin cancer, so getting all the vitamin D3 you need from sun-bathing is not a really good option for you (Do read the article Dying to Get a Tan?. Stay in the shade, pop your doctor's recommended dose of vitamin D3 supplement with a nice cup of freshly brewed green tea (or a good glass of pinot noir!) — that should do it right by you. And get yourself some over-the-counter calcium tablets. Stop wasting good money and destroying coral reefs while you poison yourself with mercury and other heavy metals.

Be well,

Chaya
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Abstracts

J Steroid Biochem Mol Biol. 2024 May;89-90(1-5):519-26.

Anti-tumor activity of calcitriol: pre-clinical and clinical studies.

Trump DL, Hershberger PA, Bernardi RJ, Ahmed S, Muindi J, Fakih M, Yu WD, Johnson CS.

Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

1,25-Dihydroxycholecalciferol (calcitriol) is recognized widely for its effects on bone and mineral metabolism. Epidemiological data suggest that low Vitamin D levels may play a role in the genesis of prostate cancer and perhaps other tumors. Calcitriol is a potent anti-proliferative agent in a wide variety of malignant cell types. In prostate, breast, colorectal, head/neck and lung cancer as well as lymphoma, leukemia and myeloma model systems calcitriol has significant anti-tumor activity in vitro and in vivo. Calcitriol effects are associated with an increase in G0/G1 arrest, induction of apoptosis and differentiation, modulation of expression of growth factor receptors. Glucocorticoids potentiate the anti-tumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. Calcitriol potentiates the antitumor effects of many cytotoxic agents and inhibits motility and invasiveness of tumor cells and formation of new blood vessels. Phase I and II trials of calcitriol either alone or in combination with carboplatin, taxanes or dexamethasone have been initiated in patients with androgen dependent and independent prostate cancer and advanced cancer. Data indicate that high-dose calcitriol is feasible on an intermittent schedule, no dose-limiting toxicity has been encountered and optimal dose and schedule are being delineated. Clinical responses have been seen with the combination of high dose calcitriol+dexamethasone in androgen independent prostate cancer (AIPC) and apparent potentiation of the antitumor effects of docetaxel have been seen in AIPC. These results demonstrate that high intermittent doses of calcitriol can be administered to patients without toxicity, that the MTD is yet to be determined and that calcitriol has potential as an anti-cancer agent.

PMID: 15225831
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Blood Journal Article

Blood. 2024 Apr 1;101(7):2454-60. Epub 2024 Nov 21.

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.

Pepper C, Thomas A, Hoy T, Milligan D, Bentley P, Fegan C.

Department of Haematology, Llandough Hospital, Penarth, Vale of Glamorgan, 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 LD(50) (the concentration of EB1089 required to kill 50% of cells) value (+/- SD) of 2.1 x 10(-8) M (+/- 1.4 x 10(-8) 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.

PMID: 12446453
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