The simple interpretation is this that having a higher level of serum B12 (above 455.41) means you are 1.85 times more likely to die over a time period of 8.2 years than someone whoâs level is less than 338.85. USA.gov. Ter Arkh. Although previous research has identified an association between lower levels of vitamins and chronic liver disease, this is the first study to correlate folate and B12 levels to NASH severity, explained the researcher, writing in Nutrients. I strongly suspect this is a sleight of hand to try and justify their conclusions. There is a special vitamin tablet for patients with kidney disease (both on dialysis and not). Kidney (Renal) failure (acute or chronic) occurs when the kidneys no longer function well and the end stage of kidney failure. To be fair, the correction appears to have been done thoroughly. Guest post by GP David Morris – Unravelling the alarming misinformation in a recent study on vitamin B12. And indeed, nearly three-quarters of cancer patients exhibit elevated B12 levels. B12 is a coenzyme involved in the catabolism of methylmalonic acid and homocysteine, and B12 supplementation may lower homocysteine levels. More importantly we have good evidence that renal problems are a cause of elevated B12. The tablet includes much lower doses of folic acid, vitamins B12 and B6. This was a âpost hoc longitudinal cohort studyâ which simply means that the authors looked back at a population they had studied, split the population into groups (cohorts) and performed an analysisÂ -in this case B12 levels and overall mortality. Having indicated that they excluded injectable B12 from the study and that they had no data on oral supplementation then the authors make some exceptionally questionable statements.Â In the discussion they acknowledge âthe underlying mechanism of the association of plasma concentration of Vitamin B12 with mortality is incompletely understoodâ but then go on to say âThe results of this study could also be clinically interpreted in the context of oral vitamin B12 supplementation.â. The original PREVEND study has shown Â that elevated urinary microalbuminuria is a marker for renal dysfunction in the general population not just in those with diabetes. Washington, DC: National Academy Press, 1998. The kidneys play an important role in TC2 metabolism. Methylmalonic acid and homocysteinemia are key biomarkers for the diagnosis of functional deficits in vitamin B12. Follow b12 deficiency blog on WordPress.com. As I discuss later very high levels of B12 are caused by a number of serious diseases, not vice versa. Clinicopathological Analysis and Prognostic Assessment of Transcobalamin I (TCN1) in Patients with Colorectal Tumors. Hypercobalaminemia can yield clinical signs indicating functional and qualitative vitamin B12 deficiency. Some people have symptoms of kidney failure while others do not; however whey they do occur they include shortness of breath, generalized swelling, and congestive heart failure. Folate, vitamin B12, and homocysteine concentrations during pregnancy are important factors for early development and may persistently influence kidney function in the offspring. Abstract. If we see an association between smoking and lung cancer and we have seen an increase in population smoking and an increase in lung cancer cases then this is coherent. A review paper titled âThe Pathophysiology of Elevated Vitamin B12 in Clinical Practiceâ6 is an excellent summary: Solid tumours and non-malignant liver disease. I've googled and found out that elevated b12 levels can be a sign of leukemia, liver or kidney disease. Using statistical techniques they âcorrectedâ for any differences in these groups that were not simply due to B12 e.g. the body uses methylcobalamin to mop up cyanide by forming cyanocobalamin that can then be excreted. The reason for raising cyanocobalamin supplementation as a potential issue is because despite the common claim that the amount of cyanide that is released and needs to be detoxified is miniscule, in fact in renal impairment there is evidence to indicate concern. Vitamin B-6 can also be taken as a supplement, typically as an oral capsule, tablet or liquid.People who have kidney disease or conditions that prevent the small intestine from absorbing nutrients from foods (malabsorption syndromes) are more likely to be vitamin B-6 deficient. Normally when this process takes place, methionine receives a return methyl group from vitamin B12 or folic acid. In total there were 5571 patients studied after they had excluded people that were not suitable. In particular when you look at the graphs of survival (figure 3 in the paper for those that wish to look it up) then the overall survival rate in quartile 2 and 3 is better than quartile 1 until just before 5 years in the study and then it starts to creep just below quartile 1Â â I can think of no biological reason why this should be so. 2013 Jun;106(6):505-15. doi: 10.1093/qjmed/hct051. This study, which despite its title is NOT a general population study, does not provide any evidence whatsoever that supplementing Â B12 has any potential to be dangerous. Correction is very important â if, for example, one of the cohorts by coincidence had many more smokers this would distort the results and invalidate the study. Your kidneys filter wastes and excess fluids from your blood, which are then excreted in your urine. In the case of B12 levels and mortality we have no evidence to support this. It is notable that the Institute of Medicine. 1, Auce A. 6, 9, 11–14 Most patients with chronic kidney disease … To be clear that actual increased risk of dying if you have high B12 levels (as defined by this study) is 2.28% NOT 85%. I got blood work back that states everything is pretty much normal. What are the causes of high Vitamin B12 other than supplementation? doi:10.1001/jamanetworkopen.2019.19274. [The significance of an elevated cobalamin concentration in the blood]. The pathophysiology of elevated vitamin B12 in clinical practice QJM. J Patient Exp. It stand to reason that these individuals are at higher risk of several diseases due to their functional B12 deficiency despite elevated serum levels. For the purposes of mathematics and statistics this might be fine but the real life issue of some patients having potentially very high levels is not corrected by this. (Note -I am aware that there are ongoing debates and studies in this areas that might indicate benefit but the point is that the evidence we were using at the time was flawed.). 2019 May 3;2(5). The mechanism being white blood cells (granulocytes) releasing B12 binding proteins. However, MMA concentrations not only depend on adequate vitamin B12 status, but also relate to renal function and endogenous production of propionic acid. A kidney stone usually causes major pain as it passes through the urinary tract. We recently published a thorough review on Elevated B12 as a Marker for Disease.While our review was focused on studies looking at mortality, a reader pointed out a 2019 meta-analysis that found an association between elevated B12 levels and the incidence of lung cancer. We clearly know that inappropriate supplementation of some nutrients can be harmful e.g. Hashimoto’s disease is an autoimmune disorder that can cause hypothyroidism, or underactive thyroid. There are all sorts of things beyond just taking extra B12 that can raise your levels: liver problems, kidney problems, bone marrow problems, and cancer. This study was in patients in a renal study and so inevitably had more patients in it with renal impairment- for this reason there was an over representation of people with excessive protein in the urine. The lower the P value the less likely the result is by chance. After adjusting for age, high blood pressure, and markers of kidney disease, the risk was closer to 25 percent. There are 5 stages of chronic kidney disease. Petition update – Your help is needed for the next stage! FREE help options here…. Hence we see the polemic statements âhigh B12 levels nearly double your death rate.â. However, Â in this current age of increasing censorship of all that is not mainstream pharmaceutical based medicine it is clearly important we robustly challenge bad science and bad reporting. I think this has been sufficient to âset the hares runningâ by those with vested interests against any supplementation recommendation. The ratio of death rates is called the âHazard Ratio.â, Here there is an important observation- although they split the population into the 4 quartiles they presented the results with the lowest and highest quartile but merged the second and third quartile. 5 Biological gradient âthis an alternative way of saying âdose responseâ. In summary this study does not in fact meet any of the Braford Hill criteria that would suggest causation rather than association. of lung cancer. 3. 2. Compared to vitamin B12 deficiency, renal dysfunction itself appears to cause only a modest elevation in serum MMA. Epub 2013 Feb 27. LÃ¸land KH et al Am J Cardiol. P value is the probability value â this indicates the odds of something being by chance or a real difference. the high B12 is the first indicator of malignancy. excess iron -due to causing mitochondrial dysfunction -and of course excess of the fat soluble vitamins are harmful. I cant help wondering if it was a good idea to have reinstated the b12 as I have never felt so Ill or COVID-19 is an emerging, rapidly evolving situation. I think it is a fairly reasonable rule of thumb that the more statistical adjustment that is required in a study then the less confidence we can have that the results are meaningful in real life. It widely acknowledged that B12 deficiency is rife, often hard to determine and definitively a cause of higher risk of a number of serious diseases â dementia, vascular disease, neurological disease, mental health disorders etc. Association of elevated vitamin B 12 with oncohematological diseases in a cohort of 79,524 patients from Latvia. Kidney Disease Diagnosis. 2015 Feb 2;16:7. doi: 10.1186/1471-2369-16-7. With many thanks to Dr Morris for this blog. Serum Creatinine: Creatinine is a waste product in your blood that comes … Your iron levels are low: Most Chronic Kidney Disease and Dialysis patients contend with low levels of iron and anemia due to the fact that their kidneys do not produce enough EPO (prompts the bone marrow to make red blood cells).As a result, the bone marrow makes fewer red blood cells, causing Anemia and leading patients to feel weak as well as experience lower energy levels. Kidney stones. With this disease, your immune system attacks your thyroid. While low serum cobalamin levels do not necessarily imply deficiency, an abnormally high serum cobalamin level forms a warning sign requiring exclusion of a number of serious underlying pathologies. Definition. Firstly the differences are quite small between the groups even from the lowest to highest quartile which makes it questionable how you would expect to see a difference in outcomes. In the FAVORIT trial, about 4000 renal transplant recipients will be randomized to a combination of folate, vitamin B12 and vitamin B6 or placebo, and in the HOST trial, more than 2000 patients with advanced renal disease are43]. Hence potentially well people could have been included in the study but in whom the high B12 actually indicated a significant life threatening disease was about to manifest. Compared to vitamin B12 deficiency, renal dysfunction itself appears to cause only a modest elevation in serum MMA. Hence, we aimed to investigate to what extent variation in MMA levels is explained by vitamin B12 and eGFR and whether MMA levels … Park J, Choi JH, Choi HJ, Hong SH, Park CS, Choi JH, Chae MS. BMJ Open. McMahon GM et al BMC Nephrol. 2006;354:1567-77. They did the very first work proving smoking caused cancer. 1. Lonn E et al. NIH This review reflects the potential importance of the vitamin B12 assay as an early diagnostic marker of these diseases. However no one believes that yellow fingers Â cause lung cancer â the common link clearly is smoking. Liver disease due to release of B12 from damaged liver cells into the bloodstream Kidney disease due to impaired function of the kidneys to excrete excess B12 Increased levels of transcobalamin, which is a transporter of B12 in the bloodstream Inflammatory conditions: rheumatoid arthritis, lupus Methods: Individuals with plasma B12 measurements were sampled from The Health Improvement Network primary care database, UK. Findings from intervention trials support this conclusions. Â The simple answer is no and I will detail this below. The reason I strongly suspect this is what happened is that I can see no other reason when you have the data for all quartiles to merge two of them. The thyroid is … Chronic kidney disease causes: When your kidneys don't work well for longer than 3 months, doctors call it chronic kidney disease. Your doctor will start by asking questions about your family medical history, which medications you're taking, and if you notice that you're peeing more or less than normal. Kidney disease is called a ‘silent disease’ as there are often few or no symptoms. Institute of Medicine. 1 Strength â death rate from lung cancer in smokers was 9-10 times that of non-smokers. However, the implications for early cancer detection in primary care have not been assessed. You can see from the figures above that the population level of high urinary albumin is 24.3% but in the study population the rate was 70% (of the 11,163 â we cannot determine the actual percentage of the final 8,592 but it is unlikely to be less.) That means my gfr is 105. Regression analysis revealed that the moderate elevation of HCY and CYS in transplant patients is mainly a consequence of impaired remethylation of HCY to methionine with activated transsulfuration, whereas the mildly elevated MMA level is attributable to renal dysfunction. Serefhanoglu S, Aydogdu I, Kekilli E, Ilhan A, Kuku I. Ann Hematol. Jose L. Flores-Guerrero, MD, et al JAMA Netw Open. â these are not simply associations as we can see mechanisms by which low B12 is causative.Â We also know that a failure to intervene in timely manner with B12 deficiency can lead to irreversible neurological damage.Â Any attempt to scaremonger people away from addressing these risks with appropriate supplementation is clearly to be lamented. what comes first?Â This is an extremely important point with respect to high B12 levels because we know that a significant number of serious diseases (see below) cause high B12 levels. Kidney disease, or diabetic nephropathy, develops progressively in patients with type 2 diabetes. This has been found in other research where elevated plasma vitamin B12 concentrations have been found in patients with cancers and with liver, kidney, autoimmune, and infectious diseases. It is tempting to simply dismiss the false interpretations and polemic claims against supplementation and simply move on. 7 Coherence â does the association fit with other facts? Background: Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. Dr MorrisÂ qualified as a medical doctor in 1994 and spent six years in hospital medicine â mostly in general adult medicine, but also in paediatrics and Accident and Emergency. There is a special vitamin tablet for patients with kidney disease (both on dialysis and not). Secondly we have no idea of the distribution of B12 levels in the highest quartile as they do not give the rangeÂ â there may be any number of patients in there with extremely high B12 levels which as I will come to later may well be very relevant and skew the results. A recent paper published in the Journal of the America Medical Association (JAMA) 1 has been reported by various sources as indicating the B12 supplementation may be harmful and that âthis paper adds to the growing body warning people that vitamin supplements may not have as much benefit as they claim.â Insider Health leads with the headline âHigh levels of B12 were associated with an increased risk of early death in a new studyâ and the web page address for this article is actually titled âB12 supplements could be lethal in high doses, study finds.â. Although previous research has identified an association between lower levels of vitamins and chronic liver disease, this is the first study to correlate folate and B12 levels to NASH severity, explained the researcher, writing in Elevated levels are also associated with diabetes, hypertension, and cardiovascular disease; it was found that elevated levels are associated with elevated serum C-reactive protein (CRP), which could reflect an inflammatory and atherogenic milieu, possibly an alternative cause for elevated serum alkaline phosphatase. Hematologic disorders like chronic myelogeneous leukemia, promyelocytic leukemia, polycythemia vera and also the hypereosinophilic syndrome can result in elevated levels of cobalamin. This is why Hill and Doll reported that smoking caused lung cancer, not just that they were associated. Hyperparathyroidism is an excess of parathyroid hormone in the bloodstream due to overactivity of one or more of the body's four parathyroid glands. support the use of MMA determination in the diagnosis of vitamin B12 deficiency in renal patients. demonstrated that 25-hydroxyvitamin D values are <30 ng/ml, believed be the lower limit of normal, in the majority of patients with CKD. According to the Mayo Clinic, "Vitamin B12, or cobalamin, helps nerve cells, red blood cells and is used in the creation of DNA." However, the chance of winning the lottery with one ticket is 1 in 45,057,474 i.e. Elevated levels of B12 are rare and often caused by disease, most commonly decreased liver function or diseases of the blood. In fact, the authors point out that elevated B12 levels may indicate liver damage or chronic kidney disease, suggesting an effect of ongoing disease rather than a cause. Firstly the study excluded anyone on B12 injections- this is clearly important because if supplementation is harmful then would be the ones we should most interested in.Â Secondly, with regard to oral or sublingual supplementation, prescribed or over the counter, they simply had no way of knowing. If you have chronic kidney disease, you and your doctor will manage it together. 6 Plausibility â this is easy to understand â when we observe smoking and lung cancer together it is plausible that one causes the other. However, the implications for early cancer detection in primary care have not been assessed. The tablet includes much lower doses of folic acid, vitamins B12 and B6. is intravenous hydroxycobalamin. This nicely presents a rising mortality rate with each rise in B12. Chronic kidney disease, also called chronic kidney failure, describes the gradual loss of kidney function. The second paper suggested a possible increased association of hip fracture with B vitamins but in fact no statistical increase with B12 supplementation and again no comment on mortality. It was shown that injecting methylcobabalamin increased the serum levels of cyanocobalamin which was then removed from the body by urinary excretion i.e. The relative âriskâ of winning the lottery if you buy two lottery tickets instead of one is 100% higher or 2.0 times more likely. You may not have any symptoms in … However if we consider the possibility that the 3rd quartile had a lower mortality than the 2nd (or indeed than the 1st) then this nice tidy observation that higher B12 equals higher mortality is harder to justify. Early kidney disease usually has no symptoms, so you should get tested for kidney disease if you have any of these risk factors: diabetes, high blood pressure, heart disease, or a family history of kidney failure. Cyanocobalamin being excreted by the kidney at three times the rate of methylcobalamin. 2020 Jul 22;9(8):2326. doi: 10.3390/jcm9082326. He holds Membership of the Royal College of Physicians â MRCP(UK) â and has a Postgraduate Diploma in the Study of Integrative Medicine. This study was conducted in non dialysis patients, and so is Elevated levels of vitamin B12 are associated with an increased risk of death in hemodialysis (HD) patients, study findings presented at the National Kidney … Chronic kidney disease increases your risk of hyperkalemia, or high levels of potassium in your blood. Observational studies of patients with 4–10, 13–14 Patients with CKD have a risk of progression to end stage renal disease (ESRD), often requiring dialysis or kidney transplantation. BUN was 6 which is slightly low but good. This study has been following about 4500 men for 14 years. So is there a plausible mechanism by which high B12 levels might be a cause of harm? Studies have shown that raised albuminuria, even without overt renal function decline, is associated with elevated B12 3. Cyanide metabolism is abnormal in individuals with CKD due to decreased clearance [ 20 ]. Nutrients. Symptoms of kidney disease. Abnormal cholesterol levels are a hazard to the kidneys, according to the Physicians' Health Study. doi: 10.1136/bmjopen-2020-038990. This study was conducted in non dialysis patients, and so is most applicable to them. I am not an mathematician, in particular not a statistician, so I have to accept their word for it that these were the correct statistical techniques â it is however true to say (I am not claiming this for this study) that incorrectly applied statistical techniques are sometimes Â used in studies and distort the results. diseases that are more likely to kill you are causes of high B12. Receiving a Diagnosis of Pernicious Anemia: Exploring Experiences of Relationships With Health Professionals. 2010 Jun 1;105(11):1577-84. This is part of the ongoing PREVEND study (Prevention of REnal and Vascular ENd stage Disease), running in the city of Groningen, the Netherlands2 .The participants were selected by asking all inhabitants of the city of Groningen between the ages of 28 and 75 years (85,421 subjects) to send in a morning urine sample and to fill out a short questionnaire on demographics and cardiovascular history. Measuring holotranscobalamin II, an early indicator of negative vitamin B12 balance, by radioimmunoassay in patients with ischemic cerebrovascular disease. Dr Morris has significant training and experience in complementary therapies such as acupuncture and homeopathy, and ran a primary care based pain clinic for over a decade using acupuncture therapies. Note â convention says that a P value of 0.05 (1 in 20) or less is âstatistically significantâ â this means only a 1 in 20 chance of being a fluke finding. During this time he was also extensively involved in commissioning health care services. Carcinomas most frequently involved are HCC … Podzolkov VI, Dragomiretskaya NA, Dambaeva OT, Auvinen ST, Medvedev ID. Hypercobalaminemia (high serum vitamin B12 levels) is a frequent and underestimated anomaly. If you have kidney disease ask your doctor which tests you will have and how often they will be done. Chronic kidney disease Cellular Uptake of Cobalamin: Transcobalamin and the TCblR/CD320 Receptor Edward V. Quadros et al Biochimie. The title of the study is the âAssociation of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlandsâ and a cursory look at the abstract indicates no such suggestion that B12 supplementation is any way harmful and this was not even a consideration of the study. This is particularly interesting given the interpretation people have placed on the study. This review reflects the potential importance of the vitamin B12 assay as an early diagnostic marker of these diseases. | Background: Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. 40,856 subjects (47.8%) responded â 30,890 subjects had a urinary albumin concentration of <10 mg/L and 9,966 subjects had a urinary albumin concentration of > 10 mg/L. We have a biological understanding as to why these are harmful. Some subtypes of methylmalonic acidemia respond to vitamin B12. They acknowledge that there was âa right skewâ to the B12 levels â i.e. The thyroid becomes damaged and can’t make enough thyroid hormones. The link between high B12 and mortality is much more clearly explained in reverse i.e. High levels of Vitamin B12 may be too much of a good thing. Persons with low B12 levels were excluded together with … Normal ranges are 200-1100 and mine are 1590. I have 1 kidney and my creatinine is .75 which is great. Â The levels of B12 in these disease can be extremely high which would of course put them in the upper quartile of the study. Another important consideration is the possibility that elevated B12 levels and B12 supplementation may be harmful in individuals with CKD. Elevated levels of B12 can be caused by cirrhosis, scarring of the liver. A reminder the Hazard Ratio is the ratio of death rate (per 10,000 patient years) comparing to the rate in quartile one. Elevated levels of serum cobalamin may be a sign of a serious, even life-threatening, disease. Dr Morris has been a qualified doctor since 1994 â after training in internal general medicine he moved into General Practice in 2000 and practices as freelance GP and Integrative Physician. We examined the associations of folate, vitamin B12, and homocysteine concentrations during pregnancy with kidney outcomes in school-aged children. No one cause of death emerged. B12 Awareness Day 2020 In the House of Commons. Whilst low blood levels of vitamin B12 indicate deficiency in a test; elevated blood levels are also often discovered.Figures above 900 pg/ml are considered high, but certain cases have recorded four or even five figure values. I cant help wondering if it was a good idea to have reinstated the b12 as I have never felt so Ill or whether it's just a coincidence. Genetic disorders in this receptorÂ Â lead to high serum B12 levels but actual functional deficiency. 2020;3(1):e1919274. Zhu X, Yi K, Hou D, Huang H, Jiang X, Shi X, Xing C. Med Sci Monit. 2019 Aug 15;91(8):160-167. doi: 10.26442/00403660.2019.08.000378. So, elevated B12 levels may just be a marker for cancer. To explain this it is useful to consider playing the lottery â in this case winning Â is a benefit not a risk (at least in theoryâ¦ ). However, my liver tests were normal My kidney function is low too apparently. Urinary Albumin Excretion Is Associated with Renal Functional Abnormalities in a Nondiabetic Population Sara-Joan Pinto-Sietsma et al JASN October 2000, 11 (10) 1882-1888. Â Itâs easy, just post your questions, comments or feedback below. High serum cobalamin (vitamin B12) is a frequent and underestimated anomaly. 2 Consistency â do we find the association in different people, in different circumstances at different times? Vitamin B12 Test and Extremely High Blood Levels. Fiona M Callaghan et al ESPEN J. So here follows a step by step appraisal of the study in an attempt to elucidate what it actually does or does not say on this subject. Thus, haptocorrin may be a candidate factor to include in future studies of the possible pathogenic mechanisms leading to high Cbl levels in cancer patients, in particular for the novel associations demonstrated in this study. Even when all factors are corrected however we must take care not to presume causation and for this reason Sir Austin Bradford Hill, who was a British epidemiologist, set out nine criteria to prove causation â he is best known for his collaborative research with Sir Richard Doll, which linked smoking with cancer and other chronic illness. Elevated levels of vitamin B12 are associated with an increased risk of death in hemodialysis (HD) patients, study findings presented at the National … They converted the death rate in each quartile into the rate of deaths per 10,000 patient years â i.e. Are your vital B12 injections being stopped? Over 8.2 years, in quartile one the odds of dying are 2.95% (nearly 3/100) and in quartile 4 the odds are 5.23%Â (just over 5/100)Â â as outlined this is a relative risk increase of 85%, which sounds very scary, but in fact is an absolute risk increase of 2.28%. Age, high blood pressure etc any serum level, disease they acknowledge there... 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