Normal and cancerous pancreatic cells express the enzyme, 1a(OH)ase, that converts inactive vitamin D into active hormone D. [
1] Asking what benefit pancreatic cancer cells might receive from converting more of the inactive vitamin into the powerful hormone D than normal pancreas cells seems like a reasonable question to consider. The excerpt below mentions some other locations that the enzyme has been found and mentions work from a different study regarding the enzyme in the diseases sarcoidosis and psoriasis. The research article the excerpt is from focuses on the use of extra vitamin 25-D or a modified form of it as a possible way to reduce proliferation of the cancer cells.
Excerpt:
“Zehnder et al. examined the distribution of 1a(OH)ase in extra renal tissues (41). They reported specific staining for 1a(OH)ase in skin (basal keratinocytes, hair follicles), lymph nodes (granulomata), colon (epithelial cells and parasympathetic ganglia), pancreas (islets), adrenal medulla, brain (cerebellum and cerebral cortex) and placenta (decidual and trophoblastic cells). They also reported over-expression of the enzyme in disease states including psoriatic skin and sarcoidosis.” [1]
The use of extra vitamin D may not equally benefit all types of patients or possibly all types of cancer. Trials with supplements of vitamin D in live prostate cancer patients have not been found to be reliably beneficial. [2] Supplements of vitamin D and calcium have not been found to reduce fracture risk in healthy pre-menopausal women. [3] Educational materials for physicians may not include information about the risks associated with vitamin D supplements for some types of patients that are known to have risk of having low 25D values along with elevated 1,25D such as patients with sarcoidosis or cancer of the parathyroid gland.[4] [26]
Few research studies about vitamin D deficiency or effects include blood tests of both the vitamin and the hormone. The hormone form is less chemically stable and the lab test for it is more expensive than the lab test for the vitamin. Checking only the level of vitamin D for assessing deficiency is based on the assumption that the converting enzyme is carefully controlled within the kidneys and that excess hormone D won’t build up but the enzyme is also made by some types of cancer cells and white blood cells and even within the placenta of pregnant mammals.[21] If the hormone is especially important within the placenta for growing a baby than it might also be important for growing a tumor. Including less vitamin D in the diet of prostate, breast or colon cancer patients might help more than offering more. But extra vitamin D may be helpful for other patients, and checking both lab values may help to be sure a reduced blood level of 25-D isn’t because it ‘s being converted to extra 1,25-D outside of the kidney rather than being a diet or sun deficiency.
Without also checking the blood levels of 1,25-D it is impossible to know if all patients with depressed levels of 25-D are truly deficient in hormone 1,25-D or whether they simply have depressed levels of the precursor 25-D. The website, Chronic Illness Recovery.org has more information regarding having both tests performed accurately: [6] Taking too much of either form of D regularly can lead to harmful side effects and long term bone loss and soft tissue calcification problems. [20] People with typical health responses will break down some of the excess but a large dose for months can build up to an excess. The risk is increased if there is an undiagnosed problem leading to increased conversion to 1,25-D.
If someone’s diet includes fortified breakfast cereal, toast, milk, yogurt and other fortified beverages and snack bars and the fish that are naturally good sources of vitamin D then too much supplemental vitamin D may be consumed over time without a single capsule having been taken. The average healthy person would have the enzymes needed to break down the excess but chronically ill patients may not have the enzyme that deactivates hormone D. Vitamin D is fat soluble and can be stored. That aspect of vitamin D metabolism may have been critically important to health during winter months before the fortification of foods became common.
/Disclaimer – I have tried to share my concerns regarding the possible societal and personal risks of over-fortification and over-supplementation with vitamin D. If taking excess vitamin D was truly helpful than why hasn’t it helped more people who have tried it by now? Instead supplementation has been associated with an increase in cholesterol levels. [14] Some extra vitamin D is necessary and beneficial when there is an actual deficiency of both the vitamin and the hormone but it is not helpful if the vitamin D blood levels are low because the vitamin is being converted into elevated levels of the very powerful hormone D. Psoriasis [22] and sarcoidosis are painful diseases and the most effective treatment may require avoidance of the precursors to hormone D. Topical use of 1,25-D [24] and light therapy [25] has been tested for psoriasis and found beneficial so some individuals might have a problem using dietary sources of D.
Many foods and beverages are fortified with vitamin D now and the previous fortification levels of liquid milk had already largely eliminated most problems with rickets/vitamin D deficiency during childhood. [7,8,9,10,11] I screened many patients and educated regarding the need for adequate food sources of vitamin D or sunlight for years and during that time only met one child with early signs of rickets. His legs developed normally after sardines were added to his dairy free diet (milk allergy). Now bread and breakfast cereal and other nondairy beverages are also fortified with vitamin D. He would’t need to look only to sardines for vitamin D now but he would need to read labels. Unlike milk, the fortification levels for vitamin D are not set at any consistent level in the newer fortified products. A yogurt may have 50% fortification or zero extra fortification. Food fads to sell more products can be dangerous if the fortified chemical can be stored and possibly collect to dangerous levels. Those smaller percentages of fortification from the varied sandwiches and yogurts might add up over time especially if there is an undiagnosed problem leading to conversion of the vitamin to the hormone. Oat bran is safe but vitamin D in excess is not. A list of overdose side effects of vitamin D: [5]
I do have bias against excessive fortification of the food supply with vitamin D because both myself and my significant other have chronic conditions that cause depressed lab values of vitamin D and elevated levels of hormone D. That also means that I have first hand knowledge regarding what living with the side effects of elevated hormone D is like. Rickets can cause pain but so can the elevated hormone D levels and the elevated calcium levels that increased hormone D can cause. The firsthand knowledge regarding calcium, phosphorus and vitamin D physiology helped me recognize similar symptoms when they occurred in my puppy when she was sick with Parvovirus. The canine illness is frequently deadly. She only got better when I limited foods during the recovery period that were naturally rich or fortified with vitamin D and excess calcium/phosphorus. Pathogens have learned how to use our body’s natural processes for their own benefit. Trying to fight disease while providing the pathogens with the foods that they thrive on is largely a waste of effort. (Feed a fever but starve a cold. – a somewhat true old wive’s tale.)
Taking extra CLA, an essential fatty acid, [15, 16, 17] and limiting foods rich in arachidonic acid [19] may benefit individuals who are fighting prostate and breast cancer. Similar metabolic pathways may be involved with other forms of cancer or chronic disease but not necessarily. [18] Some types of pathogens have learned how to convert nutrients that normally are stored within cellular membranes into food sources. Feeding the body and starving the cancer would make more therapeutic sense than inundating the body with chemicals that kill both the healthy and unhealthy tissue.
Health care is not affordable if it focuses on symptoms and doesn’t tackle the underlying causes of disease./
- Schwartz G, et. al., “Pancreatic cancer cells express 25-hydroxyvitamin D-1a-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3,” (Carcinogenesis vol.25 no.6 pp.1015–1026, 2004) [carcin.oxfordjournals.org/content/25/6/1015.full.pdf] Excerpts: “Two samples obtained from infiltrating adenocarcinoma of the pancreas displayed robust and extensive expression of 1a(OH)ase in (Figure 2C, left two panels). High expression levels were also found in ductal breast carcinoma (Figure 2C, top right) and in a section of pediatric renal cell carcinoma (Figure 2C, bottom right). Furthermore, we found positive staining for 1a(OH)ase in the autonomic ganglia in colon and in the bile ducts of the liver (data not shown).” . . . “Our results confirm previous findings of expression of 1a(OH)ase in normal pancreas. Moreover, they demonstrate for the first time that 1a(OH)ase is also expressed in pancreatic adenocarcinoma.” [1]
- Article by Mary E. Dallas, “Calcium, Vitamin D Supplements May Pose Risks for Men With Prostate Cancer,” MedlinePlus SOURCES: Louis Potters, M.D., chair, radiation medicine, North Shore – LIJ Health System, New Hyde Park, N.Y.; Wake Forest Baptist Medical Center, news release, Aug. 7, 2012
- Article by Gina Kolata, “Calcium and Vitamin D Ineffective for Fractures, U.S. Preventive Services Task Force Says,” (June 12, 2012) NYTimes.com: [nytimes.com]
- “Physician Consideration Regarding Vitamin D,” (March 2012) MGHS, Nutrition and Medicine Committee, pdf [ww4.mgh.org] website: [ww4.mgh.org]
- “Cacitriol,” MedlinePlus [nlm.nih.gov/medlineplus/druginfo/meds/a682335.html]
- “D-Metabolites Tests” ChronicIllnessRecovery.org: [chronicillnessrecovery.org]
- Article by Katherine Doheny, “The Baby Won’t Take a Bow” (April 4, 1995) LATimes [articles.latimes.com] *Not too worried about rickets in 1995.
- Article by Janet Stobart, “Global Health Watch: Rickets showing up in some British children,” (Jan 19, 2011) LATimes: [articles.latimes.com] (*~40 children in the UK were treated for it at one hospital in 2011.) Rickets is no longer a reportable disease in the US and statistics aren’t available.
- Lazol JP, Cakan N, Kamat D. “10-year case review of nutritional rickets in Children’s Hospital in Michigan,” Clin Pediatr (Phila). 2008 May;47(4):379-84. Epub 2008 Jan 11. (*96% of the cases found were breast fed infants that weren’t receiving a supplement and ethnically may have had darker skin tones.)
- “Top children’s surgeon says ‘poverty’ bone disease has returned in Southampton,” (Nov 12, 2010) Press Release, University Hospital Southampton: [uhs.nhs.uk] Excerpt: “In my 22 years at Southampton General Hospital, this is a completely new occurrence in the south that has evolved over the last 12 to 24 months and we are seeing cases across the board, from areas of deprivation up to the middle classes, so there is a real need to get national attention focused on the dangers this presents.” […] “said Professor Nicholas Clarke, consultant orthopaedic surgeon at Southampton General Hospital and professor of paediatric orthopaedic surgery at the University of Southampton.” (*So asking what changed in the one to two year time period preceding Nov. 2010 that would affect 20% of children at all income levels would seem a pertinent question rather than assuming that suddenly 20% of children were no longer receiving vitamin D fortified products and had stopped going outside. Low calcium or phosphorus can also cause rickets, not just low vitamin D. Elevated 1,25 D levels can lead to decreased bone mineralization. Twenty percent of children may have chronic inflammatory conditions that current science doesn’t recognize or test for.)
- Steichen JJ, Tsang RC, Greer FR, Ho M, Hug G. “Elevated serum 1,25 dihydroxyvitamin D concentrations in rickets in very low-birth-weight infants,” J Pediatr. 1981 Aug;99(2):293-8. [ncbi.nlm.nih.gov] * 25D levels were low and 1,25 D levels were elevated. The infants were successfully treated with an increased amount of calcium and phosphorus but without a change in their vitamin D intake. The infant’s 25 D levels increased and the 1,25 D levels decreased after the change in calcium and phosphorus intake. These were premature infants, not average infants.
- Peter J. Malloy, J. Wesley Pike and David Feldman, “The Vitamin D Receptor and the Syndrome of Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets,” Endocrine Reviews April 1, 1999 vol. 20 no. 2 156-188 [edrv.endojournals.org/content/20/2/156.full]
- “Vitamin D3 1,25-Dihydroxyvitamin D, Interpretation” Medscape [emedicine.medscape.com] Excerpt: “In granulomatous disease such as lymphoproliferative disorders, sarcoidosis, tuberculosis, and inflammatory bowel disease, 1α-hydroxylase enzyme activity was found in macrophages as the extrarenal source of 1,25(OH)2 D. When 1α-hydroxylase is activated, it converts 25(OH)D to 1,25(OH)2 D, just as what occurs under physiologic conditions in the kidneys.[12] However, unlike the kidney, the 1α-hydroxylase in the macrophages in granulomatous diseases is not controlled by the usual physiologic regulators.”
- “Vitamin D Supplements Won’t Help Cholesterol Levels: Study,” (Sept 4, 2012) MedlinePlus: [nlm.nih.gov] SOURCES: Manish Ponda, M.D., M.S., assistant professor, clinical investigation, Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York City; Michael Holick, M.D., professor, medicine, physiology and biophysics, Boston University School of Medicine; Sept. 4, 2012, Arteriosclerosis, Thrombosis and Vascular Biology (* Vitamin D in normal metabolism is made from cholesterol and excess amounts of it are converted back into cholesterol so those who don’t need extra vitamin/hormone D are buying and taking a supplement of a slightly different form of cholesterol. Taking supplemental cholesterol is not a typical recommendation for anyone.)
- What Doctors Don’t Tell You (vol 13, issue 5): “CLA fatty acids may combat prostate cancer,” healthy.net: [healthy.net]
- Song HJ, et. al., “Conjugated linoleic acid inhibits proliferation and modulates protein kinase C isoforms in human prostate cancer cells,” Nutr Cancer. 2004;49(1):100-8 [ncbi.nlm.nih.gov]
- Ochoa JJ, et. al., “Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers,” Carcinogenesis (2004) 25 (7): 1185-1191. [carcin.oxfordjournals.org]
- Field CJ, Schley PD, “Evidence for potential mechanisms for the effect of conjugated linoleic acid on tumor metabolism and immune function: lessons from n 3 fatty acids,” Am J Clin Nutr 2004;79:1190S–8S, Full text pdf: [ajcn.nutrition.org]
- A previous article of mine, “Prostate and Breast Cancer and omega 6s and 3s,” (May 16, 2012) Gingerjens: [gingerjens.blogspot.com]
- “Hypervitaminosis D, Symptoms and presentation” Wikipedia [en.wikipedia.org]
- Chapter author, Daniel D Bickle, “Extrarenal Synthesis of 1,25-Dihydroxyvitamin D and Its Health Implications,” Vitamin D: Physiology, Molecular Biology, and Clinical Applications , Nutrition and Health 2010, pp 277-295, Ed. Michael F. Holick [link.springer.com]
- Article by John Gever, “Low Vitamin D Plus Hypertension May Worsen Cardiovascular Risks,” (Jan. 7, 2008) MedPageToday: [medpagetoday.com] Excerpt: “Dr. Wang and colleagues could not rule out the possibility that vitamin D deficiency is not causative. “Unmeasured characteristics associated with vitamin D deficiency could account for the increased cardiovascular risk,” they acknowledged. They pointed out that “an alternate explanation for the present findings is that vitamin D deficiency is a marker of chronic nonspecific illness rather than a direct contributor to disease pathogenesis.” ” (* Depressed levels of vitamin D that are associated with elevated levels of hormone D would lead to increased wasting of magnesium and hypertension is a primary symptom of magnesium deficiency. Other aspects of cardiovascular disease are also related to magnesium deficiency.)
- Morimoto S, et. al., “Inverse relation between severity of psoriasis and serum 1,25-dihydroxy- vitamin D level,” J Dermatol Sci. 1990 Jul;1(4):277-82. [ncbi.nlm.nih.gov]
- Kowalzick L, “Clinical experience with topical calcitriol, (1,25-dihydroxy-vitamin D3) in psoriasis” Br J Dermatol. 2001 Apr;144 Suppl 58:21-5. [ncbi.nlm.nih.gov]
- Amra Osmančević, “Vitamin D Status in Psoriasis Patients Treated with UVB Phototherapy,” (2009, Sahlgrenska University Hospital, Institute of Clinical Sciences at Sahlgrnska Academy)[gupea.ub.gu.se/bitstream/2077/19041/1/gupea_2077_19041_1.pdf ]
- “The parathyroid glands and vitamin D,” Chapter Five in Endocrinology: An Integrated Approach. Nussey S, Whitehead S.Oxford: BIOS Scientific Publishers; 2001. [ncbi.nlm.nih.gov/books]
Biochemistry and physiology are complicated and one answer is not going to work for every patient.
I don’t have all the answers or full access to the expensive research articles and journal subscriptions but I do have different questions. If the medical industry only asks the same questions then we will never learn how to cure or prevent chronic disease. One of the earliest symptoms of magnesium deficiency is hypertension and elevated 1,25 D levels lead to increased wasting of stored magnesium and decreased intestinal absorption of magnesium. Identifying individuals who have undiagnosed hypertension in order to stabilize them on pharmaceuticals will not be cheap or effective if the person’s hypertension was caused by magnesium deficiency. Magnesium is very inexpensive and hasn’t been known to cause side effects when added to foods or beverages. Adequate magnesium is essential for apoptosis and apoptosis is used by white blood cells to protect us from infected or precancerous cells.
True vitamin/hormone D deficiency can also be a cause for hypertension. It would be good to know for sure whether a depressed 25D level was signalling a metabolic pathway malfunction leading to elevated 1,25-D or a true combined vitamin/hormone D deficiency.
We don’t know what we don’t know. Learning requires being open to the idea that previous answers or theories might be wrong or might be wrong for some cases. Accurately testing 1,25 dihydroxy D levels in addition to 25-D would tell us whether the epidemic of low vitamin D levels is actually an epidemic of depressed vitamin D levels and elevated hormone D rather than an epidemic of actual deficiency. Or, even better, it would tell us which patients are part of the epidemic of chronic illness and which actually are low in vitamin and hormone D and would benefit from modifying their diet or starting to use a supplement.
Edited 9/28/12 8:50pm EST, edit-10/1/12
/The Short Disclaimer: Information presented on this site is not intended as a substitute for medical care and should not be considered as a substitute for medical advice, diagnosis or treatment by your physician./
