CPPS, the sun and vitamin D

Prostatitis is currently not one of the diseases thought to be related to low D levels, but many of the symptoms in CP/CPPS seem to be related to either immunological-inflammatory and/or neuromuscular problems. Anecdotal evidence and the studies mentioned earlier indicate that prostatitis symptoms worsen in winter and late spring when bodily D-vitamin stores are at their lowest. This raises the question if cold or D-vitamin insufficiency/deficiency is the cause, or maybe both? So why may vitamin D play a role?

Immuno-modulation and other properties
It was earlier believed that D3 (cholecalciferol) only use was to aid bone mineralization (calcium and phosphorus metabolism), but research has shown that it is a very “potent” and important substance for many bodily processes(1). D3 (or rather its metabolite calcitriol) is very important as mediator of gene transcription (e.g. the prostate specific antigen), immune response(2) (macrophage functions, T- and B-lymphocyte mediated response, NOS induction), blood pressure regulation, regulation of platelet aggregation, insulin production, cell cycle regulation (proliferation and differentiation) in epithelial tissues, synovial cells and many other cell types and tissues(3) (e.g. pituitary cells), and also of neuromuscular function. This is due to the almost ubiquitous vitamin D receptors (VDR).

Decreasing D-vitamin levels are associated with an increase in vulnerability to infection. Vitamin D (or rather its metabolite calcitriol) is a strong immuno-regulatory hormone (e.g inhibition of IL-1, IL-2, IL-6, IL-12, TNF-alpha, INF-gamma etc) (see Peterlik and Cross, 2005, for references) and recent research has also shown that it promotes production of several anti-microbial peptides.(4-5) Especially cathelicidins(6), which also have been shown to protect the urinary tract against infection.(7)

It is also interesting that recent cancer research has shown that calcitriol regulates “the expression of genes involved in the metabolism of prostaglandins”. It significantly represses expression of COX-2 and EP2 and FP receptors, and also up-regulates 15-hydroxyprostaglandin dehydrogenase.(8)

Diseases correlated with D
Diseases thought to be, or proven to be related with low levels of D are many cancers (stomach, colorectal, liver, gall bladder, pancreas, lung(9), female breast, prostate,(10-11) bladder, kidney(12)), tubercolosis(13), multiple sclerosis,(14-15), rheumatoid arthritis (16) (Merlino, Curtis et al.), diabetes type 1/ insulin resistance (Hypponen, Laara et al.), hyperparathyroidism,(17) systemic lupus erythematosus, osteoarthritis, ankylosing spondylitis and, possibly, fibromyalgia, SAD, schizophrenia,(18-19) Crohn’s disease, ulcerative colitis, irritable bowel syndrome, periodontitis and genigivitis,(20) and colorectal cancer.(21) Epidemiological studies (corrected for other factors) indicate that these diseases are more common and severe the more north you live.

The immune conditions above (RA, SLE, MS, IBS and diabetes) are thought to be caused by too low calcitriol (a vitamin D metabolite) levels to prevent a “pathological activation of Th-1 responses” (Peterlik and Cross, 2005).

Some of these diseases and activation of Th1 (cellular) immunity are also correlated to and overlap with CPPS and other urological problem.

Prostate cancer and D
Prostate cancer (Hanchette and Schwartz, Tuohimaa) is e.g. one of the cancers following the latitudinal pattern and D-vitamin has shown to be effective against pre-cancerous cells (Nonn et al.). The vitamin D receptor (VDR) is present in the prostate.

Muscle pain, weakness and depression
It is interesting to note that D-vitamin deficiency may manifest itself as pain and fatigue (ATP-deficiency), which also is characteristic for fibromyalgia and myofascial syndrome. A study found that people with less than 40 nmol/l walked more slowly and had more problems rising from chairs than people with more than 90 nmol/l.(22) Vitamin D has been proven effective for treating musculoskeletal pain.(23) D-vitamin insufficiency is a known cause of tiredness and depression (especially SAD).


Approximate vitamin D levels in sufferers of various diseases and conditions. Levels at the end of winter (march) and early fall (september), and lifeguards and multiple sclerosis treatedment (24) added for comparison.(25)

Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, överaktiv blåsa, köld, värme, vinter, sommar, D-vitamin, auto-immun sjukdom, Th1/Th2.
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Additional information on vitamin D
Vitamin D council
Grassroots health

References
(1) Humble M. D-vitaminbrist kanske vanligare än vi trott. Prevention och behandling skulle kunna ge oanade folkhälsoeffekter. [Vitamin D deficiency probably more common than earlier apprehended. Prevention and treatment could result in unexpected public health effects]. Läkartidningen 104(11):853-857, 2007. Article in Swedish.)
(2)van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 97(1-2):93-101, 2005.
(3) Peterlik M, Cross HS. Dysfunction of the vitamin D endocrine system as common cause for multiple malignant and other chronic diseases. Anticancer Res 26(4A):2581-2588, 2006.
(4) Cannell JJ, Vieth J, Umhau C, Holick MF, Grant B, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiology and Infection 136:1129-1140, 2006.
(5) Weber G, Ståhle M Vitamin D induces the antimicrobial protein hCAP18 in human skin. J Invest Dermatol 124(5):1080-1082, 2005.
(6) ”Cathelicidins have a very broad spectrum of activity, and promote wound healing and re-epthelialization of breaks in the skin: they are absent in chronic (non-healing) ulcers. [Heilborn JD, Nilsson MF, Kratz G, et al., The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol. 120(3): 379-89, 2003] Cathelicidins have activity against intracellular bacteria; this has been demonstrated in Mycobacterium tuberculosis [Liu PT, Stenger S, Li H, Wenzel L. et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006 Mar 24;311(5768):1770-3] Cathelicidins are active in the innate defence system of the gut, lining the mucosa and preventing attachment by epithelial-adherent bacterial pathogens. [Dann SM, Eckmann L. Innate immune defenses in the intestinal tract. Curr Opin Gastroenterol. 2007 Mar;23(2):115-20.] Cathelicidins are active in vitro against Herpes Simplex Virus and cathelicidin deficiency has been found in persons with eczema herpeticum. [Howell MD, Wollenberg A, Gallo RL. et al., Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol. 2006 Apr;117(4):836-41.]” (http://www.davidwheldon.co.uk/vit_D.html.)
(7) Chromek M, Gallo RL The antimicrobial cathelicidin protects the urinary tract against invasive bacterial infection. Nature Medicine 12:636-641, 2006.
(8) Moreno J, Krishnan AV, Swami S, Nonn L, Peehl DM, Feldman D. Regulation of prostaglandin metabolism by calcitriol attenuates growth stimulation in prostate cancer cells. Cancer Res 65(17):7917-7925, 2005.
(9) Porojnicu AC, Robsahm TE, Dahlback A, Berg JP, Christiani D, Bruland OS, Moan J. Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role? Lung Cancer. 55(3):263-270, 2007.
(10) Lagunova Z, Porojnicu AC, Dahlback A, Berg JP, Beer TM, Moan J. Prostate cancer survival is dependent on season of diagnosis. Prostate 67(12):1362-1370, 2007.
(11) Schwartz GG, Hanchette CL. UV, latitude, and spatial trends in prostate cancer mortality: all sunlight is not the same (United States). Cancer Causes Control. 17(8):1091-1101, 2006.
(12) Tuohimaa P, Pukkala E, Scélo G, Olsen JH, Brewster DH, Hemminki K, Tracey E, Weiderpass E, Kliewer EV, Pompe-Kirn V, McBride ML, Martos C, Chia KS, Tonita JM, Jonasson JG, Boffetta P, Brennan P. Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: Vitamin D as a possible explanation. Eur J Cancer 43(11):1701-12, 2007.
(13) People with D-vitamin deficiency are much easier infected, and an increase in active D in the body helps fight the infection (remember the sanatorium treatments with lots of “fresh air”, i.e. sunlight !)
(14) There is also concern that nutritional factors help promote MS. Like: cereals, legumes, dairy products, too little Omega-3 and too much Omega-6, antioxidant deficiencies and low fibre (from fruits and vegetables) consumption (A Embry, http://www.direct-ms.org).
(15) Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296(23):2832-2838, 2006.
(16) Cutolo M, Otsa K, Laas K, Yprus M, Lehtme R, Secchi ME, Sulli A, Paolino S, Seriolo B. Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol. 24(6):702-704, 2006.
(17) Chronic vitamin-D insufficiency or deficiency may cause any of the parathyroid glands to become “stuck in high gear” while trying to keep calcium levels in the body within “safe” limits, which may cause a lot of problems when you really do get D-vitamin see www.parathyroid.com for more info.
(18) Carrión-Baralt JR, Fuentes-Rivera Z, Schmeidler J, Silverman JM. A case-control study of the seasonality effects on schizophrenic births on a tropical island. Schizophr Res. 71(1):145-53, 2004
(19) Carrión-Baralt JR, Smith CJ, Rossy-Fullana E, Lewis-Fernández R, Davis KL, Silverman JM. Seasonality effects on schizophrenic births in multiplex families in a tropical island. Psychiatry Res 142(1):93-7, 2006
(20) Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? BJN 89:552-572, 2003.
(21) Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19 year prospective study in men. Lancet 1:307-309, 1985.
(22) Dawson-Hughes B. Vitamin D, how much is enough and why. 5th International Symposium on Nutritional Aspects of Osteoporosis. Lausanne, May 14-17, 2003.
(23) Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, non-specific muscoloskeletal pain. Mayo Clinic Proc. 78(12):1463-1470, 2003.
(24) Kimball SM, Ursell MR, O'Connor P, Vieth R. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 86:645–5, 2007.
(25) From left to right: Chronic pain/fibromyalgia, pain in general, rickets, osteporosis/osteopaenia, respiratory tract infection/ILI, connective tissue disease, polymyalgia rheumatica/giant cell arteritis, inflammatory arthritis/rheumatism in general, osteoarthritis, propensity of falling, general muscle weakness, fatigue, melanoma stage IV, breast cancer, cardio-vascular disease, diabetes mellitus, multiple sclerosis, CPPS (hypothetical), march levesl found in many people living in Europe and northern USA, september levels found in people tanning or moving about a lot in the sun, americam life-guards, people in MS remission due to vitamin D treatment.