Prolonged inflammatory conditions can result in "Anemia of chronic disease". Mechanistically this has been proposed to be due to altered iron metabolism, however, several studies have suggested that it may be due to functional deficiency in vitamin B12, folate and iron, particularly if there is chronic inflammation, such as is seen in conditions such as psoriasis, rheumatoid arthritis, or similar conditions involving prolonged activation of macrophages. Several chronic inflammatory diseases are associated with the development of vitamin B12 deficiency. Thus, https://bell-ross-replica.goodtimepics.com/ vitamin B12 deficiency has been associated with various chronic inflammations such as multiple sclerosis, psoriasis, eczema, chronic fatigue syndrome, rheumatoid arthritis, Ankylosing spondylitis, Crohn's disease, IBD, and ulcerative colitis.
Early studies on the inflammatory process in rheumatoid arthritis revealed over production of the vitamin B12 carrier protein, transcobalamin, which was subsequently shown to be produced by activated macrophages (Sattar and Das, 1991). The continued stimulation of macrophages in RA would eventually lead to B12 deficiency, which is common in RA (Petterson et al, 1998; Hernanz et al, 1999; Yxfeldt et al, 2003; Woolf and Manore 2008). Further, the constant production of nitric oxide by macrophages, potentially leads to inactivation of vitamin B12 due to production of the inactive NO-B12 derivative.
The observations of increased production of Transcobalamin by monocytes has also been shown to occur in other inflammatory conditions such as Ulcerative colitis, Crohn's disease, and shigellosis (Rachmilewitz etal, 1978, 1990). Elevated Transcobalamin levels have also been found in systemic lupus erthematosus, and were inversely correlated with reduced serum vitamin B12 levels (Molad et al. 1990). Elevated levels of activated macrophages are also found in fat tissue, and may contribute to the vitamin B12 deficiency seen in obesity. Activated macrophages also produce elevated amounts of nitric oxide, which has been shown to bind strongly to oxidized Co(II)B12, and would contribute to inactivation of vitamin B12 through the generation of NO-B12. This would lead to a paradoxical functional deficiency in vitamin B12, where serum levels of vitamin B12 would be high, yet the B12 would be inactive.
During the course of IBD, the wall of the intestine becomes inflamed and is no longer able to absorb vitamin B12 via the VB12-intrinsic factor mediated uptake system. As a result patients with chronic IBD, such as those with Crohn's Disease and Ulcerative Colitis soon become deficient in vitamin B12 This vitamin B12 deficiency in turn can lead to even less control of the inflammation, thus exacerbating the disease. Dietary supplements containing vitamin B12 can no longer be absorbed and so vitamin B12 must be given either by injection or some other route, such as transdermal application.
Apart from the important role that vitamin B12 plays in the functioning of the brain and nervous system and in red blood cell production, vitamin B12 also has an important role in the control of inflammation. Vitamin B12 deficiency has been implicated in several inflammatory diseases such as dementia, Alzheimer's Disease, neuritis, multiple sclerosis and Parkinson's disease. In addition it has also been found that administration of high doses of vitamin B12 may be beneficial in the treatment of chronic inflammatory conditions such as atopic dermatitis, eczema, psoriasis, osteoarthritis, diabetic neuropathy, fibromyalgia and Chronic Fatigue Syndrome.. There is also evidence that vitamin B12 has potential use in the treatment of chronic pain.
Chronic expression of nitric oxide is associated with various inflammatory conditions including diabetes, multiple sclerosis, psoriasis, eczema, rheumatoid arthritis, Crohn's disease, IBD, and ulcerative colitis. Nitric oxide has been shown to react with Vitamin B12 and it is possible that the vitamin B12 deficiency that has been associated with dementia, Alzheimer's disease, neuritis, multiple sclerosis and Parkinson's disease is due to the constant release of nitric oxide, which then reacts with circulating vitamin B12. This reaction may in itself lead to vitamin B12 deficiency, thus exacerbating the condition. Studies have shown that chronic fatigue patients have high levels of nitric oxide and peroxynitrite, which may be related to the symptoms associated with CFS. Continued production of nitric oxide is known to negatively affect brain function and pain sensitivity, which may be related to its association in CFS, MS, Alzheimer's disease, neuritis and Parkinson's disease..
One of the initiating factors in inflammation is the production of NFκB, which in turn triggers the release of pro-inflammatory cellular signaling molecules (cytokines). NFκB also controls the production of audemars piguet royal oak offshore replica inducible nitric oxide synthase (iNOS), cyclo-oxgenase 2 (COX-2), growth factors, inhibitors of apoptosis. It has recently been shown that high doses of vitamin B12can inhibit the production of NFκB, which could potentially combine with nitric oxide scavenging by vitamin B12' to further reduce inflammation.
Treatment of inflammation with high doses of Vitamin B12 cannot be achieved using oral vitamin B12 supplements due to the limited uptake capacity for vitamin B12 in the intestine. For this reason, vitamin B12 deficiency or inflammatory conditions such as fibromyalgia are normally treated with vitamin B12 injections. Recently a topical form of vitamin B12 has been developed which is a specially formulated preparation that is an easy to apply, needle-free delivery system to the skin of the patient. This pain-free form of delivery greatly increases the patient comfort experienced during the administration of the medication and allows for self-medication without the need for medical staff or any special training. Oral supplementation with vitamin B12 does not provide enough vitamin B12 to overcome vitamin B12 deficiency due to the limited uptake capacity of the intestine for vitamin B12, hence there is a requirement for higher initial doses of vitamin B12 to be supplied either by injection or via the topical vitamin B12 formulation. Clinical trials with topical preparations of vitamin B12 have shown that it provides considerable relief for patients with psoriasis and ezcema. In addition, the topical formulation is particularly suited to patients with chronic inflammatory diseases who may have gastro-intestinal problems, such as gastric ulcers, atrophic gastritis, Crohn?s Disease and Ulcerative Colitis, or who are on Metformin? medication, which can often lead to vitamin B12 deficiency.
The very condition that causes vitamin B12 deficiency in IBD also means that vitamin B12 supplementation by traditional means is largely ineffective. Furthermore, once deficiency has manifested itself high dose supplementation is required to reverse the progression of the deficiency and associated conditions. Recently a topical form of vitamin B12 has been developed which is a specially formulated preparation that is an easy to apply, needle-free delivery system to the skin of the IBD patient. This pain-free form of delivery greatly increases the patient comfort experienced during the administration of the medication and allows for self-medication without the need for medical staff or any special training. In addition, the topical formulation is particularly suited to patients who may have gastro-intestinal problems, such as Crohn?s Disease and Ulcerative Colitis which often lead to vitamin B12 deficiency.
It is known that in vitamin B12 deficiency there is an over-production of serotonin, which is the precursor for the production of melatonin. The possibility exists, therefore, that the cause of IBS is actually vitamin B12 deficiency. This would result in the observed alterations in serotonin production and processing, plus the reduced production of melatonin and the accompanying irregular gastro-intestinal mobility, poor control of local anti-inflammatory responses and subsequent abdominal pain. Whilst treatment with melatonin may partially over-come the melatonin deficiency it would be less effective in controlling the increased serotonin production. Further, the alterations in the gut wall would potentially reduce the effectiveness of oral treatment with vitamin B12, and hence injection of B12 or transdermal application (B12 oils) would be more effective. The very condition that causes vitamin B12 deficiency in IBD also means that vitamin B12 supplementation by traditional means is largely ineffective.
Afman LA, Van Der Put NM, Thomas CM, Trijbels JM, Blom HJ. 2001 Reduced vitamin B12 binding by transcobalamin II increases the risk of neural tube defects. QJM Mar;94(3):159-66
Arnalich F, Zamorano AF, Benito-Urbina S, Gijon-Banos J, De Miguel E, Pena JM, Vazquez JJ. 1990 Increased apotranscobalamin II levels in rheumatoid arthritis.Br J Rheumatol Jun;29(3):171-3
Bjorksten KS, Dige N, Nexo E. 2001 Long-term memory correlates negatively with plasma transcobalamin in healthy elderly with normal plasma cobalamin levels. Int J Geriatr Psychiatry;16(4):439-41
Brada N, Gordon MM, Wen J, Alpers DH. 2001 Transfer of cobalamin from intrinsic factor to transcobalamin II. J Nutr Biochem ;12(4):200-206
Carmel R. 1980 Transcobalamin and inflammatory bowel disease. Gastroenterology Jun;78(6):1660-1
Christensen PA, Brynskov J, Gimsing P, Petersen J. 1983 Vitamin B12 binding proteins (transcobalamin and haptocorrin) in serum and synovial fluid of patients with rheumatoid arthritis and traumatic synovitis. Scand J Rheumatol;12(3):268-72
Fehr J, De Vecchi P 1985 Transcobalamin II: a marker for macrophage/histiocyte proliferation. Am J Clin Pathol Sep;84(3):291-6
Gilbert, H. S., Weinreb, N., 1976 Increased circulating levels of transcobalamin II in Gaucher?s disease. N. Engl. J. Med., 295, 1036-1101
Gimsing, P., Frost-Larsen, K., Isager, H. et al., 1982 Cobalamin-binding proteins in serum and saliva from patients with Sjogren?s syndrome. Scand. J. Rheumatol., 11:1-4.
Hernanz et al. Increased plasma levels of homocysteine and other thiol compounds in rheumatoid arthritis women. Clin Biochem. 1999 32: 65-70
Januchowski Evaluation of topical vitamin B12 for the treatment of childhood eczema J. Altern Complement Med. 2009 15: 387-9
Lambert D, Benhayoun S, Adjalla C, Gelot MA, Renkes P, Felden F, Gerard P, Belleville F, Gaucher P, Gueant JL, Nicolas JP. 1996 Crohn's disease and vitamin B12 metabolism. Dig Dis Sci Jul;41(7):1417-22
Melmed RN, Rachmilewitz B, Schneider A, Rachmilewitz M 1986 The modulation of transcobalamin II (TC-II) production by cyclic adenosine 3',5'-monophosphate in the murine macrophage cell line J774: relationship to growth behaviour. J Cell Physiol Mar;126(3):430-4
Molad, T., Rachmilewitz, B., Sidi, Y., Pinkhas, J., Weinberger, A. 1990 Serum cobalamin and transcobalamin levels in systemic lupus erythematosus. Am. J. Med., 88: 141-4.
Mozaffari et al. Implications of melatonin therapy in Irritable Bowel Syndrome: a systematic review. Curr Pharm Des. 2010 16:3646-55
Petterson et al. Serum homocysteine and methylmalonic acid in patients with rheumatoid arthritis and cobalaminopenia. J Rhematol 1998 25: 859-63
Pozo etal. Melatonin, a potential therapeutic agent for smooth muscle-related pathological conditions and aging. Curr. Med Chem. 2010 17: 4150-65
Rabinowitz R, Rachmilewitz B, Rachmilewitz M, Schlesinger M. 1982 Production of transcobalamin II by various murine and human cells in culture. Isr J Med Sci Jul;18(7):740-5
Rachmilewitz et al. Production of TCII (vitamin B12 transport protein) by mouse mononuclear phagocytes. Blood 1978: 1089-98
Rachmilewitz et al. Transcobalamin II level in peripheral blood monocytes - a biochemical marker in inflammatory diseases of the bowel. Gastro 1980 78: 43-6
Rachmilewitz, B., Schlesinger, M., Rabinowitz, R., and Rachmilewitz, M 1979 The origin and clinical implications of vitamin B12 binders ? the transcobalamins. In ?Vitamin B12? Eds. B. Zagalak and W. Friedrich. Walter de Gruyter, Berlin. Pp 765-776.
Rachmilewitz, B., Rachmilewitz, M. 1977 Serum transcobalamin II concentration (Letter), N. Engl. J. Med., 295, 1174
Radwan etal. Is melatonin involved in the Irritable Bowel Syndrome? J Physiol Pharmacol 2009 60: 67-70
Sattar MA, Das KC. 1991 Plasma vitamin B12 binding proteins correlate with disease activity in patients with rheumatoid arthritis. Med Lab Sci Jan;48(1):36-42
Seetharam B, Bose S, Li N. 1999 Cellular import of cobalamin (Vitamin B-12). J Nutr;129(10):1761-4
Souied EH, Benhamou N, Sterkers M, Oubraham H, Coscas G, Soubrane G, Zittoun J, Echenne B, Rothenberg S 2001 Retinal degeneration associated with congenital transcobalamin II deficiency. Arch Ophthalmol;119(7):1076-7
Vreugdenhil G, Lindemans J, van Eijk HG, Swaak AJ. 1992 Elevated serum transcobalamin levels in anaemia of rheumatoid arthritis: correlation with disease activity but not with serum tumour necrosis factor alpha and interleukin 6. J Intern Med 1992 May;231(5):547-50
Tr?ter-Schr?der, M., Hitzig, H., Grob, P. J., Kenny, A. B., 1978 Increased unsaturated transcobalamin II in active autoimmune disease, Lancet 2, 238-239.
Jacob, E., Baker, S. J., Herbert, V. 1980 Vitamin B12- binding proteins. Physiol. Rev., 60: 918-60.
Woolf and Manore Elevated plasma homocysteine and low vitamin B6 status in non-supplementing older women with rheumatoid arthritis J Am Die Assoc. 2008 108:443-53
Yxfeldt et al. Homocysteine in patients with rheumatoid arthritis in relation to inflammation and B-vitamin treatment Scand J Rheumatol 2003 32: 205-10
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