Few studies about vitamin D and its relation to bladder overactivity and incontinence have been done despite the association between vitamin D and muscle weakness and coordination. The only two I have found show a correlation with decreasing vitamin D levels and female pelvic floor disorders incl. urinary incontinence(1) and risk of onset of overactive bladder.(2) Especially with age. The studies have been made on women only, but there is no reason to believe men should differ in this respect.
Another study has also shown that bladder cells (“bladder epithelium and stromal cells along with vascular endothelial cells”) contain vitamin D receptoirs (as most of the other cells of the body also do) and that treatment with vitamin D analogues “inhibits basal and androgen-stimulated human bladder cell growth and enhances their apoptosis” and “prevent[s] starvation-induced cell phenotype modification”.(3) All factors thought to cause overactive bladder.
Thus different lines of evidence point at low vitamin D levels being a possible causative agent. As CPPS show distinct seasonality with summertime improvement, the studies are interesting and one can hope vitamin D levels will be studied in CPPS sufferers.
On a personal note I have been treating myself with vitamin D since 2008 (after noting the distinct seasonality of my symptoms) and have noted a distinct remission of all CPPS problems
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, överaktiv blåsa, värme, sommar, D-vitamin, inkontinens.
____________
(1) Badalian SS, Rosenbaum PF. Vitamin D and pelvic floor disorders in women. Obstet gynecol 115(4):795-803, 2010.
(2) Dallosso HM, McGrother CW, Matthews RJ, Donaldson MM. Leicestershire MRC incontinence study group. Nutrient composition of the diet and the development of overactive bladder: a longitudinal study in women. Neururol urodyn 23:204-210, 2004.
(3) Crescioli C et al. Human Bladder as a Novel Target for Vitamin D Receptor Ligands. J Clin Endocrin Metabol 90(2):962-972, 2005.
Showing posts with label seasonality. Show all posts
Showing posts with label seasonality. Show all posts
Friday, April 9, 2010
Saturday, March 27, 2010
CPPS, darkness and melatonin
There is also the possibility that winter darkness worsens CPPS. Instead of absence of vitamin D. or possibly both. So how may winter darkness affect CPPS? Perhaps through melatonin level variation.
Melatonin is thought to affect the “inner clock” (synchronizing the photoperiod of an organism), reproduction, metabolism, thermoregulation and immune function. The effect on the “inner clock” is known since long, while the effects on the immune system are a pretty new area of research.
Recent research indicate that melatonin has an immuno-stimulating effect. It stimulates the production of e.g. IL-1, IL-2, IL-6, IL-12 and gamma-interferon, but not IL-4. Human studies “suggest that melatonin may favour a Th1 cell response”. Th1 regulation needs, as we just saw, vitamin D.
Excessive “melatonin production may be involved in glucocorticoid resistance”, which usually causes inflammation. Sufferers of rheumatoid arthritis (RA) have been found to have higher levels and longer night time peaks of melatonin and thus a more marked up-regulation of immune function than controls. RA sufferers do also normally have more pain and/or muscle/joint stiffness in the morning than in the evening.
What is interesting, is that levels of melatonin, some cytokines and interleukins was higher the more northerly RA-patients lived, thus explaining the higher prevalence of RA in Balto-Scandinavian countries compared to Mediterranean countries. The same study also measured cortisol levels and found no differences in those. “A diurnal rhythmicity in healthy humans between cellular (Th1 type) or humoral (Th2 type) immune responses has been found and related to immunomodulatory actions of cortisol and melatonin.” (1,2)
As CP/CPPS shows a similar south to north gradient it would be very interesting to study if CP/CPPS sufferers show a similar pattern of melatonin secretion. Decreased night-time melatonin secretion during the longer summer daylight above 50 degrees of latitude may explain summer (and early fall) remission in addition to vitamin D. RA has also been shown to improve with higher levels of vitamin D.(3) A bit odd though as a low night-time melatonin (and if the nighttime peak occurs too early or late) level is correlated with e.g. seasonal depression and prostate cancer growth, while CPPS is not correlated with prostate cancer but with winter time depression. On the other hand high night-time levels are correlated with higher anxiety, which seems more common during winter in CPPS.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, överaktiv blåsa, köld, värme, vinter, sommar, D-vitamin, auto-immun sjukdom, Th1/Th2, melatonin.
__________________
(1) Cutolo M, Maestroni GJM. The melatonin-cytokine connection in rheumatoid arthritis.Ann Rheum Dis 64:1109-1111, 2005.
(2) Cutolo M, Sulli A, Pizzorni C, Secchi ME, Soldano S, Seriolo B, Straub RH, Otsa K, Maestroni GJ. Circadian rhythms: glucocorticoids and arthritis. Ann N Y Acad Sci. 1069:289-299, 2006.
(3) Pelajo CF, Lopez-Benitez JM, Miller LC. Vitamin D and Autoimmune Rheumatologic Disorders. Autoimmun Rev. 2010 Feb 8. [Epub ahead of print]
Melatonin is thought to affect the “inner clock” (synchronizing the photoperiod of an organism), reproduction, metabolism, thermoregulation and immune function. The effect on the “inner clock” is known since long, while the effects on the immune system are a pretty new area of research.
Recent research indicate that melatonin has an immuno-stimulating effect. It stimulates the production of e.g. IL-1, IL-2, IL-6, IL-12 and gamma-interferon, but not IL-4. Human studies “suggest that melatonin may favour a Th1 cell response”. Th1 regulation needs, as we just saw, vitamin D.
Excessive “melatonin production may be involved in glucocorticoid resistance”, which usually causes inflammation. Sufferers of rheumatoid arthritis (RA) have been found to have higher levels and longer night time peaks of melatonin and thus a more marked up-regulation of immune function than controls. RA sufferers do also normally have more pain and/or muscle/joint stiffness in the morning than in the evening.
What is interesting, is that levels of melatonin, some cytokines and interleukins was higher the more northerly RA-patients lived, thus explaining the higher prevalence of RA in Balto-Scandinavian countries compared to Mediterranean countries. The same study also measured cortisol levels and found no differences in those. “A diurnal rhythmicity in healthy humans between cellular (Th1 type) or humoral (Th2 type) immune responses has been found and related to immunomodulatory actions of cortisol and melatonin.” (1,2)
As CP/CPPS shows a similar south to north gradient it would be very interesting to study if CP/CPPS sufferers show a similar pattern of melatonin secretion. Decreased night-time melatonin secretion during the longer summer daylight above 50 degrees of latitude may explain summer (and early fall) remission in addition to vitamin D. RA has also been shown to improve with higher levels of vitamin D.(3) A bit odd though as a low night-time melatonin (and if the nighttime peak occurs too early or late) level is correlated with e.g. seasonal depression and prostate cancer growth, while CPPS is not correlated with prostate cancer but with winter time depression. On the other hand high night-time levels are correlated with higher anxiety, which seems more common during winter in CPPS.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, överaktiv blåsa, köld, värme, vinter, sommar, D-vitamin, auto-immun sjukdom, Th1/Th2, melatonin.
__________________
(1) Cutolo M, Maestroni GJM. The melatonin-cytokine connection in rheumatoid arthritis.Ann Rheum Dis 64:1109-1111, 2005.
(2) Cutolo M, Sulli A, Pizzorni C, Secchi ME, Soldano S, Seriolo B, Straub RH, Otsa K, Maestroni GJ. Circadian rhythms: glucocorticoids and arthritis. Ann N Y Acad Sci. 1069:289-299, 2006.
(3) Pelajo CF, Lopez-Benitez JM, Miller LC. Vitamin D and Autoimmune Rheumatologic Disorders. Autoimmun Rev. 2010 Feb 8. [Epub ahead of print]
CPPS, the sun and vitamin D part 2
Calcium, cancer and pituitary
Can rising parathyroid hormone concentrations or changed calcium metabolism / homeostasis with decreasing D-vitamin levels trigger CP/CPPS or some of its symptoms? Maybe, as vitamin D and “calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific… attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor” causing “perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system.”(1) Calcium deficiency may also promote breast, prostate and colorectal cancer. Adequate calcium levels may also regulate Th1 (cellular) immune response.
It is interesting that the vitamin D receptor (VDR) is present in the pituitary, which is central in diuretic and prostaglandin regulation. Especially as there are many indications of pituitary dysfunction in CPPS sufferers.
Nutritional adequacy
More or less everyone living north of the 60th parallel will have insufficient levels of vitamin D or out-right deficiency by the end of winter. This is because there is not enough sunlight from November to March. This is also exacerbated by indoors living and clothing during the summer months.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, överaktiv blåsa, köld, värme, vinter, sommar, D-vitamin, auto-immun sjukdom, Th1/Th2.
___________________
(1) Peterlik M, Cross HS. Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest 35(5):290-304, 2005.
Can rising parathyroid hormone concentrations or changed calcium metabolism / homeostasis with decreasing D-vitamin levels trigger CP/CPPS or some of its symptoms? Maybe, as vitamin D and “calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific… attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor” causing “perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system.”(1) Calcium deficiency may also promote breast, prostate and colorectal cancer. Adequate calcium levels may also regulate Th1 (cellular) immune response.
It is interesting that the vitamin D receptor (VDR) is present in the pituitary, which is central in diuretic and prostaglandin regulation. Especially as there are many indications of pituitary dysfunction in CPPS sufferers.
Nutritional adequacy
More or less everyone living north of the 60th parallel will have insufficient levels of vitamin D or out-right deficiency by the end of winter. This is because there is not enough sunlight from November to March. This is also exacerbated by indoors living and clothing during the summer months.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, överaktiv blåsa, köld, värme, vinter, sommar, D-vitamin, auto-immun sjukdom, Th1/Th2.
___________________
(1) Peterlik M, Cross HS. Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest 35(5):290-304, 2005.
Sunday, March 21, 2010
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.
_____________
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.
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.
_____________
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.
Sunday, December 20, 2009
Vitamin D and immune seasonality
Many diseases show an increased incidence with less sun exposure (i.e. living in the north) which may be correlated insufficient levels vitamin D. Does vitamin D affect immune regulation? Yes, an increasing amount of evidence shows that vitamin D and individual vitamin D receptor polymorphism (“gene variants”) are very important for immune regulation. The VDR is present in almost every cell in the body. Much of the basic research has been done with so called VDR null (3) mice and it indicates that VDR differences in vitamin D deficiency cause different risk for respiratory diseases, stomach ulcers, auto-immunity, cancers (breast, skin, colon, prostate, pancreas etc), hypertension, IBS, diabetes, increased thrombogenicity (“clot forming”), thyroid disturbances, rheumatic disease, MS (4) (which “is essentially unknown at the equator”), osteoporosis, diffuse muscular pain, ostearthrosis, connective tissue disorders, caries, skin disorders (including acne), rickets, SLE, myopathy (“weak muscles”), schizophrenia and on and on and on.
Main ways of action of vitamin D (or rather its metabolites) are immuno-regulatory. It regulates immunity by suppressing the proliferation of immunoglobulin, inhibit differentiation of dendritic cells (“the most potent of antigen presenting cells”), slowing B cell differentiation and inhibit Th1 cell proliferation (innate, cellular response) thus decreasing e.g. IFN-gamma and IL-2 productiion. It may also increase Treg and IL-4, 5 and 10 production thus in sum inducing a more Th2 (adaptive, humoral) biased response and attenuating any excessive Th1 inflammatory response.. It does also regulate and inhibit Th17 response. Innate immunity is also enhanced by expression of antimicrobial peptides (AMPs, e.g. cathelicidin and defensins). Innate (cellular) immunity is important for epithelial integrity of e.g. lungs, gengiva, bladder, skin (epidermis) and intestine. VDR-driven immune response is strongly impaired in vitamin D deficiency. Other effects are anti-neoplastic (regulation of cell growth and differentiation) and inhibition of angiogenesis (growth of new blood vessels, especially into tumors). Influenza and auto-immune disease are typically worsening (exacerbating / flaring) in winter (3) and spring, and improving in summer and fall.(4-12)
125 micrograms vitamin D per day reach steady state at about 150 nmol/l 25(OH)D after 3 months and 250 micrograms at about 200 nmol/l after 3 months (starting point was 70 nmol).(13) Intoxication has been observed at levels above 375 nmol/l (50000 IU/day). Skin production of vitamin D is self-limiting so intoxication is not possible by tanning. Hyperthyroidism increases 25(OH)D metabolism rates. (Holick)
Useful amounts of vitamin D are only present in certain wild fat fish. E.g. fresh *wild* salmon that contains 600-1000 IU per 100 grams. Darkskinned African skin equals approximately a sun protection factor 15 sun screen (Holick).
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, immunity, seasonality, D-vitamin, auto-immune disease.
_________________
(1) Caveat: murine immune system differs from human in certain important aspects.
(2) In a trial reported by J Burton, at the 2009 meeting of American Academy of Neurology, vitamin D supplementation for, on average, 14000 IU/day induced remission and about a halved relapse rate.
(3) Immune response is upregulated during winter to counter environmental adversities. In the wild the net effect is a relative immune suppression (due to limited energy availability / high energy expense), but in laboratory conditions this may not be the case.
(4) Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M. Vitamon D and human health: lesosn from vitamin D receptor null mice. Endocr Rev 29(6):726-776, 2008.
(5) Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis and inflammatory bowel disease. Prog Biophys Mol Biol. 92(1):60-64, 2006.
(6) Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 92(1):4-8, 2006.
(7) Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81:353-373, 2006.
(8) Holick MF. Vitamin D deficiency. NEJM 357(3):266-281, 2007.
(9) Mouyis M, Ostor AJK, Crisp AJ, Ginawi A, Halsall DJ, Shenker N, Poole KES. Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology 47:1348-1351, 2008.
(10) Nelson RJ. Seasonal immune function and sickness response. Trends Immunol 25(4):187-192, 2004.
(11) Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 94(1):26-34, 2009.
(12) White JH. Vitamin D signaling, infectious diseases and regulation of innate immunity. Inf Immun 76(9):3837-3843, 2008.
(13) Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204-210, 2003.
Main ways of action of vitamin D (or rather its metabolites) are immuno-regulatory. It regulates immunity by suppressing the proliferation of immunoglobulin, inhibit differentiation of dendritic cells (“the most potent of antigen presenting cells”), slowing B cell differentiation and inhibit Th1 cell proliferation (innate, cellular response) thus decreasing e.g. IFN-gamma and IL-2 productiion. It may also increase Treg and IL-4, 5 and 10 production thus in sum inducing a more Th2 (adaptive, humoral) biased response and attenuating any excessive Th1 inflammatory response.. It does also regulate and inhibit Th17 response. Innate immunity is also enhanced by expression of antimicrobial peptides (AMPs, e.g. cathelicidin and defensins). Innate (cellular) immunity is important for epithelial integrity of e.g. lungs, gengiva, bladder, skin (epidermis) and intestine. VDR-driven immune response is strongly impaired in vitamin D deficiency. Other effects are anti-neoplastic (regulation of cell growth and differentiation) and inhibition of angiogenesis (growth of new blood vessels, especially into tumors). Influenza and auto-immune disease are typically worsening (exacerbating / flaring) in winter (3) and spring, and improving in summer and fall.(4-12)
125 micrograms vitamin D per day reach steady state at about 150 nmol/l 25(OH)D after 3 months and 250 micrograms at about 200 nmol/l after 3 months (starting point was 70 nmol).(13) Intoxication has been observed at levels above 375 nmol/l (50000 IU/day). Skin production of vitamin D is self-limiting so intoxication is not possible by tanning. Hyperthyroidism increases 25(OH)D metabolism rates. (Holick)
Useful amounts of vitamin D are only present in certain wild fat fish. E.g. fresh *wild* salmon that contains 600-1000 IU per 100 grams. Darkskinned African skin equals approximately a sun protection factor 15 sun screen (Holick).
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, immunity, seasonality, D-vitamin, auto-immune disease.
_________________
(1) Caveat: murine immune system differs from human in certain important aspects.
(2) In a trial reported by J Burton, at the 2009 meeting of American Academy of Neurology, vitamin D supplementation for, on average, 14000 IU/day induced remission and about a halved relapse rate.
(3) Immune response is upregulated during winter to counter environmental adversities. In the wild the net effect is a relative immune suppression (due to limited energy availability / high energy expense), but in laboratory conditions this may not be the case.
(4) Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M. Vitamon D and human health: lesosn from vitamin D receptor null mice. Endocr Rev 29(6):726-776, 2008.
(5) Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis and inflammatory bowel disease. Prog Biophys Mol Biol. 92(1):60-64, 2006.
(6) Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 92(1):4-8, 2006.
(7) Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81:353-373, 2006.
(8) Holick MF. Vitamin D deficiency. NEJM 357(3):266-281, 2007.
(9) Mouyis M, Ostor AJK, Crisp AJ, Ginawi A, Halsall DJ, Shenker N, Poole KES. Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology 47:1348-1351, 2008.
(10) Nelson RJ. Seasonal immune function and sickness response. Trends Immunol 25(4):187-192, 2004.
(11) Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 94(1):26-34, 2009.
(12) White JH. Vitamin D signaling, infectious diseases and regulation of innate immunity. Inf Immun 76(9):3837-3843, 2008.
(13) Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204-210, 2003.
Saturday, December 19, 2009
The immune system (enteric, gender, seasonality)
The following blog posts will discuss basic immune function and the possible connections with CPPS.
The immune system is divided in two arms: innate and adaptive. Both of which contain cellular (macrophages, natural killer cells etc) and humoral (antibodies) immune components. Cellular immunity protects mainly against intracellular bacteria, protozoans, fungi and many viruses), while humoral immunity protects against multicellular parasites, extracellular bacteria, certain viruses, ceratin toxins and allergens. A popular concept of immunity is the Th1/Th2/Th17-hypothesis.(1-3) In additon to these two arms, an oft forgotten an very important part of the immune system is the enteric immune system.
Not only does the gut have a massive nervous system (see below), it is also the biggest immune system in the body. The gut-associated lymphoid tissue comprises about 70 percent of the mucosal barrier (most of the rest protects the lungs). And that is not suprising as the gut has to withstand an endless stream of pathogens and occasional toxins. Not only invaders from outside the body but also the about over 100 trillion organisms that live in the gut. The maternal intestinal microbiota (both organisms and a large number of “intestinally derived bacterial components”, N.B. not antibodies, but genetic material) is passed to the newborn trough the breast milk.(4) Ingested probiotics may modulate intestinal pain and the immune system by normalizing cytokine ratios.(5)
The brain and the viscera communicate with each other to coordinate behavior and emotional responses (due to evolutionary reasons like territorial marking, not stop to pee while hunted, panic, anxiety, and so on).and visceral activity. Pathological changes (e.g. bacterial infection, tissue damage, distension of the colon and others) in the viscera affect the forebrain.
Immune activity shows a circadian rhythm with cellular/Th1 prevalence during sleep (maximum activity coincides with nocturnal cortisol maximum) and humoral/Th2 prevalence during daytime. Diseases more common / worse during daytime are e.g. stroke, arrhythmias, seizures, sepsis and asthma.
A seasonal pattern of increased immune activity during winter with humoral bias, to counter wintertime stress induced immune suppression, and cellular bias during summer is also postulated.(6,7) Children (and especially foetuses) are more humoral/Th2 biased than adults (8) (and sex differences are minimal before puberty). Adult men generally have a more Th1-biased response, due to high androgen levels, that gets more Th2-biased with age as testosterone levels decrease. Female response is generally more Th2-biased due to the high levels of estrogens that are both pro-inflammatory (a pro-fibrotic response) and “immunosupportive”. Thus the same infectious (or adjuvant) insult may cause a stronger anti-inflammatory response in men.(9)
Estrogens correlate with increased incidence of depression, axiety and auto-immune disorders (women are 2-9 times more likely to suffer from pain disorders, RA and SLE). Female immune response varies with the different phases of the menstrual cycle, pregnancy and contraceptive usage.(10)
Much confusion casued by animals studies arises from the fact that acute and chronic phase response are not distinguished. These differences between acute and chronic phases and phases of the menstrual cycle are seldom considered in general research even if sex differences have been accounted for (which in itself is not done as much as it should).
Nocturia induced sleep disruption and androgen alterations may both lead to immune changes worsening CPPS and explain the sickness behaviour seen in CPPS sufferers. Also the fact that CPPS generally remits during summer (when sun-stimulated vitamin D production shift the immune response towards an anti-inflammatory response), may indicate that CPPS is an immune related disorder. Possibly a disorder of Th1-driven (cellular) inflammatory immunity.
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, enteric, gender immune dimorphism, immunity, Th1/Th2, androgens, estrogens, nocturia, seasonality.
______________________
(1) Steinman L. A rush to judgment on Th17. J Exp Med 205(7): 1517–1522, 2008.
(2) Kidd P. Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Altern Med Rev 8(3):223-246, 2003
(3) Steinman L. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage. Nature medicine 13(2):139-145, 2007
(4) Perez PF, Dore J, Leclerc M, Levenez F, Benyacoub J, Serrant P, Segira-Roggero I, Schiffrin EJ, Donnet-Hughes A. Bacterial imprinting on the neonatal immune system: lessons from maternal cells? Pediatrics 119(3):E724-732, 2007.
(5) Marchesi J, Shanahan F. The normal intestinal microbiota. Curr Opin Infect Dis 20:508-513, 2007.
(6) Nelson RJ, GE Demas GE, Klein SL, Kriegsfeld LJ. Seasonal Patterns of Stress, Immune Function, and Disease. Cambridge University Press, 2002.
(7) Nelson RJ. Seasonal immune function and sickness responses Trends in Immunology 25(4):187-192, 2004.
(8) Petrovsky N. Towards a unified model of neuroendocrine–immune interaction. Immunol Cell Biol 79:350–357, 2001
(9) Fairweather D, Frisancho-Kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. Am J Pathol 173:600-609, 2008.
(10) Darnall BD, Suarez EC. Sex and gender in psychoneurimmunology research: past, present and future. Brain Behav Immun 23:595-604, 2009.
The immune system is divided in two arms: innate and adaptive. Both of which contain cellular (macrophages, natural killer cells etc) and humoral (antibodies) immune components. Cellular immunity protects mainly against intracellular bacteria, protozoans, fungi and many viruses), while humoral immunity protects against multicellular parasites, extracellular bacteria, certain viruses, ceratin toxins and allergens. A popular concept of immunity is the Th1/Th2/Th17-hypothesis.(1-3) In additon to these two arms, an oft forgotten an very important part of the immune system is the enteric immune system.
Not only does the gut have a massive nervous system (see below), it is also the biggest immune system in the body. The gut-associated lymphoid tissue comprises about 70 percent of the mucosal barrier (most of the rest protects the lungs). And that is not suprising as the gut has to withstand an endless stream of pathogens and occasional toxins. Not only invaders from outside the body but also the about over 100 trillion organisms that live in the gut. The maternal intestinal microbiota (both organisms and a large number of “intestinally derived bacterial components”, N.B. not antibodies, but genetic material) is passed to the newborn trough the breast milk.(4) Ingested probiotics may modulate intestinal pain and the immune system by normalizing cytokine ratios.(5)
The brain and the viscera communicate with each other to coordinate behavior and emotional responses (due to evolutionary reasons like territorial marking, not stop to pee while hunted, panic, anxiety, and so on).and visceral activity. Pathological changes (e.g. bacterial infection, tissue damage, distension of the colon and others) in the viscera affect the forebrain.
Immune activity shows a circadian rhythm with cellular/Th1 prevalence during sleep (maximum activity coincides with nocturnal cortisol maximum) and humoral/Th2 prevalence during daytime. Diseases more common / worse during daytime are e.g. stroke, arrhythmias, seizures, sepsis and asthma.
A seasonal pattern of increased immune activity during winter with humoral bias, to counter wintertime stress induced immune suppression, and cellular bias during summer is also postulated.(6,7) Children (and especially foetuses) are more humoral/Th2 biased than adults (8) (and sex differences are minimal before puberty). Adult men generally have a more Th1-biased response, due to high androgen levels, that gets more Th2-biased with age as testosterone levels decrease. Female response is generally more Th2-biased due to the high levels of estrogens that are both pro-inflammatory (a pro-fibrotic response) and “immunosupportive”. Thus the same infectious (or adjuvant) insult may cause a stronger anti-inflammatory response in men.(9)
Estrogens correlate with increased incidence of depression, axiety and auto-immune disorders (women are 2-9 times more likely to suffer from pain disorders, RA and SLE). Female immune response varies with the different phases of the menstrual cycle, pregnancy and contraceptive usage.(10)
Much confusion casued by animals studies arises from the fact that acute and chronic phase response are not distinguished. These differences between acute and chronic phases and phases of the menstrual cycle are seldom considered in general research even if sex differences have been accounted for (which in itself is not done as much as it should).
Nocturia induced sleep disruption and androgen alterations may both lead to immune changes worsening CPPS and explain the sickness behaviour seen in CPPS sufferers. Also the fact that CPPS generally remits during summer (when sun-stimulated vitamin D production shift the immune response towards an anti-inflammatory response), may indicate that CPPS is an immune related disorder. Possibly a disorder of Th1-driven (cellular) inflammatory immunity.
CPPS, prostatit, kroniskt bäckenbottensmärtsyndrom, nokturi, trängningar, enteric, gender immune dimorphism, immunity, Th1/Th2, androgens, estrogens, nocturia, seasonality.
______________________
(1) Steinman L. A rush to judgment on Th17. J Exp Med 205(7): 1517–1522, 2008.
(2) Kidd P. Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Altern Med Rev 8(3):223-246, 2003
(3) Steinman L. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage. Nature medicine 13(2):139-145, 2007
(4) Perez PF, Dore J, Leclerc M, Levenez F, Benyacoub J, Serrant P, Segira-Roggero I, Schiffrin EJ, Donnet-Hughes A. Bacterial imprinting on the neonatal immune system: lessons from maternal cells? Pediatrics 119(3):E724-732, 2007.
(5) Marchesi J, Shanahan F. The normal intestinal microbiota. Curr Opin Infect Dis 20:508-513, 2007.
(6) Nelson RJ, GE Demas GE, Klein SL, Kriegsfeld LJ. Seasonal Patterns of Stress, Immune Function, and Disease. Cambridge University Press, 2002.
(7) Nelson RJ. Seasonal immune function and sickness responses Trends in Immunology 25(4):187-192, 2004.
(8) Petrovsky N. Towards a unified model of neuroendocrine–immune interaction. Immunol Cell Biol 79:350–357, 2001
(9) Fairweather D, Frisancho-Kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. Am J Pathol 173:600-609, 2008.
(10) Darnall BD, Suarez EC. Sex and gender in psychoneurimmunology research: past, present and future. Brain Behav Immun 23:595-604, 2009.
Saturday, March 28, 2009
Seasonality etc part 2
Why these cycles? It is not uncommon in disease.
Many disorders show seasonality, but it is seldom explained. In an article in Medical hypotheses the authors (1) suggest that “temporal variations of autonomic balance” affect disease. What they essentially suggest is an expansion of the Th1/Th2 balance hypothesis of disease (which is a convenient simplification). If the immune system is over-balanced towards Th1 response (aka parasympathetic activity, Th1 bias, innate or [intra-]cellular immunity) it supposedly responds well to cancer cells, viruses, yeasts and intracellular pathogens but less well to extracellular pathogens. On the other hand auto-immune disease is more common.
If on the other hand immune response is prevalently Th2 (aka sympathetic activity, Th2 bias, adaptive or humoral immunity) it combats bacteria and extracellular organisms. But allergy and asthma is more common.
Th1/Th2 response shows a circadian rhythm with Th1 prevalence during sleep and Th2 prevalence during daytime. Diseases more common / worse during daytime (thus worsening because of increased Th2 and decreased Th1 response) are e.g. stroke, arrhythmias, seizures, sepsis and asthma. A seasonal pattern of increased Th2 bias during winter and Th1 bias during summer is also postulated.
Disease disrupting sleep will dampen Th1 response and thus worsen disorders affected by this.
They also suggest that Th1 bias is stronger in childhood and senescence (old age).
Their ideas are interesting as CPPS causes sleep disruption, remits during summer and is more common in mid-life. All of which suggest that Th2 bias worsens CPPS.
I’ll get back to this topic when discussing vitamin D, sleep and the HPA axis.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, biologiska rytmer, Th1/Th2-balans
_________________
(1) Medical Hypotheses 63(1):155-177, 2004. Articles by AJ Yun, PY Lee and KA Bazar.
Many disorders show seasonality, but it is seldom explained. In an article in Medical hypotheses the authors (1) suggest that “temporal variations of autonomic balance” affect disease. What they essentially suggest is an expansion of the Th1/Th2 balance hypothesis of disease (which is a convenient simplification). If the immune system is over-balanced towards Th1 response (aka parasympathetic activity, Th1 bias, innate or [intra-]cellular immunity) it supposedly responds well to cancer cells, viruses, yeasts and intracellular pathogens but less well to extracellular pathogens. On the other hand auto-immune disease is more common.
If on the other hand immune response is prevalently Th2 (aka sympathetic activity, Th2 bias, adaptive or humoral immunity) it combats bacteria and extracellular organisms. But allergy and asthma is more common.
Th1/Th2 response shows a circadian rhythm with Th1 prevalence during sleep and Th2 prevalence during daytime. Diseases more common / worse during daytime (thus worsening because of increased Th2 and decreased Th1 response) are e.g. stroke, arrhythmias, seizures, sepsis and asthma. A seasonal pattern of increased Th2 bias during winter and Th1 bias during summer is also postulated.
Disease disrupting sleep will dampen Th1 response and thus worsen disorders affected by this.
They also suggest that Th1 bias is stronger in childhood and senescence (old age).
Their ideas are interesting as CPPS causes sleep disruption, remits during summer and is more common in mid-life. All of which suggest that Th2 bias worsens CPPS.
I’ll get back to this topic when discussing vitamin D, sleep and the HPA axis.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, biologiska rytmer, Th1/Th2-balans
_________________
(1) Medical Hypotheses 63(1):155-177, 2004. Articles by AJ Yun, PY Lee and KA Bazar.
Tuesday, March 17, 2009
Seasonality, cyclicity and circadian rhythm
There seems to be a distinct seasonality in CP/CPPS. Overall symptoms worsen the more northerly you live. Over the year symptoms improve from about may to august and worsen from october to april. Overlying this longer cycle there is anecdotal evidence of a shorter cycle of about 3-6 weeks for dysuria and of a diurnal cycle were symptoms, especially dysuria and muscle pain, are worse in the morning and improve during the day.
I'll revisit this topic later.
I'll revisit this topic later.
Monday, February 23, 2009
Seasonal symptom cluster
This is an intriguing aspect of CP/CPPS symptoms. Question is what it means? Many auto-immune diseases show seasonal patterns superimposed on shorter term flare-remission patterns.
• General seasonal variation with all symptoms worsening during winter and improving during summer.
• Cold/winter exacerbated micturition problems (cold induced diuresis?). Caused by cold seat, cold feets, immersion in cold water and shivering etc.
• Cold/winter tension-induced muscular pains and aches (myalgia)?
• Cold/winter induced arthralgia (joint aches, but joints are not swollen or reddish)?
• Cold/winter induced fibrinogen production? This is inferred from the fact that a majority of treatments have an anti-thrombotic component and research (e.g. 1-2).
• Winter related dryness of eyes and nose? (Note that winter air is drier than summer air due to lower absolute humidity. Average water content below zero degress Celsius is below 5 grams water per kg air.)
• The micturition problems do also seem to follow a cyclical pattern (duration of about three weeks?) of exacerbations and improvement.
• There may also be a weak circadian rhythm.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, symptomkluster, biologiska rytmer
_______________
(1) Rudnicka AR, Rumley A, Lowe, GDO, Strachan DP. Diurnal, Seasonal, and Blood-Processing Patterns in Levels of Circulating Fibrinogen, Fibrin D-Dimer, C-Reactive Protein, Tissue Plasminogen Activator, and von Willebrand Factor in a 45-Year-Old Population. Circulation 115:996-1003, 2007.
(2) Crawford VLS, McNerlan SE, Stout RW. Seasonal changes in platelets, fibrinogen and factor VII in elderly people. Age and Ageing 32:661-665, 2003.
Some examples of human chronobiology:
One study showed e.g. that cortisol peaked in december, FT3 (thyroid hormone) and growth hormone in april, insulin in february, while prolactin and parathyroid hormone showed no variation. (Del Ponte A, Guagnano MT, Sensi S. Time-Related Behaviour of Endocrine Secretion: Circannual Variations of FT3, Cortisol, Hgh and Serum Basal Insulin in Healthy Subjects. Chronobiol Int 1(4):297-300, 1984.)
(Minor update/edit march 4th 2009)
• General seasonal variation with all symptoms worsening during winter and improving during summer.
• Cold/winter exacerbated micturition problems (cold induced diuresis?). Caused by cold seat, cold feets, immersion in cold water and shivering etc.
• Cold/winter tension-induced muscular pains and aches (myalgia)?
• Cold/winter induced arthralgia (joint aches, but joints are not swollen or reddish)?
• Cold/winter induced fibrinogen production? This is inferred from the fact that a majority of treatments have an anti-thrombotic component and research (e.g. 1-2).
• Winter related dryness of eyes and nose? (Note that winter air is drier than summer air due to lower absolute humidity. Average water content below zero degress Celsius is below 5 grams water per kg air.)
• The micturition problems do also seem to follow a cyclical pattern (duration of about three weeks?) of exacerbations and improvement.
• There may also be a weak circadian rhythm.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, symptomkluster, biologiska rytmer
_______________
(1) Rudnicka AR, Rumley A, Lowe, GDO, Strachan DP. Diurnal, Seasonal, and Blood-Processing Patterns in Levels of Circulating Fibrinogen, Fibrin D-Dimer, C-Reactive Protein, Tissue Plasminogen Activator, and von Willebrand Factor in a 45-Year-Old Population. Circulation 115:996-1003, 2007.
(2) Crawford VLS, McNerlan SE, Stout RW. Seasonal changes in platelets, fibrinogen and factor VII in elderly people. Age and Ageing 32:661-665, 2003.
Some examples of human chronobiology:
One study showed e.g. that cortisol peaked in december, FT3 (thyroid hormone) and growth hormone in april, insulin in february, while prolactin and parathyroid hormone showed no variation. (Del Ponte A, Guagnano MT, Sensi S. Time-Related Behaviour of Endocrine Secretion: Circannual Variations of FT3, Cortisol, Hgh and Serum Basal Insulin in Healthy Subjects. Chronobiol Int 1(4):297-300, 1984.)
(Minor update/edit march 4th 2009)
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