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. An increased blood level of vitamin B12 is sometimes caused by kidney disease, including diabetic kidney disease.  |  Normal ranges are 200-1100 and mine are 1590. Elevated levels of vitamin B12 are associated with an increased risk of death in hemodialysis (HD) patients, study findings presented at the National Kidney … 1997;12:1622–8.  The levels of B12 in these disease can be extremely high which would of course put them in the upper quartile of the study. N Engl J Med. The following article by Dr David Morris unravels and corrects what lies behind the headline:  “High levels of B12 were associated with an increased risk of early death in a new study”. 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. Gavars D.* 1, Perminov D. 1, Tauckels E. 1, Lindenberga I. All the other data we have indicates no cause for concern with B12 supplementation other than cyanocobalamin in renal impairment, but this is not a formulation I would ever recommend. demonstrated that 25-hydroxyvitamin D values are <30 ng/ml, believed be the lower limit of normal, in the majority of patients with CKD. Fiona M Callaghan et al ESPEN J. With many thanks to Dr Morris for this blog. They were followed up for median (average) time of 8.2 years the range of follow up being 7.7.to 8.9 years, so nearly a decade. 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 – he is best known for his collaborative research with Sir Richard Doll, which linked smoking with cancer and other chronic illness. It is notable that the Institute of Medicine. Folate, vitamin B12, and homocysteine concentrations during pregnancy are important factors for early development and may persistently influence kidney function in the offspring. I.e. Chronic kidney disease increases your risk of hyperkalemia, or high levels of potassium in your blood. Persons with low B12 levels were excluded together with persons with … It fails even on its basic premise that high B12 is a cause of increased mortality. Charitably we could describe this as lazy reporting/journalism although my inclination is to describe it as deliberately biased reporting. In the case of smoking the longer and the more you smoke the higher the risk. After adjusting for age, high blood pressure, and markers of kidney disease, the risk was closer to 25 percent. [Hypervitaminemia B12 (high level of cobalamin): physiopathology, role and interest in clinical practice]. We’d love your comments on this article. Such falsely high valued of serum vitamin B12 levels are observed in myeloproliferative disease, acute hepatitis, severe alcoholic liver disease, and cirrhosis. 2011 Dec;40(12 Pt 1):1120-7. doi: 10.1016/j.lpm.2011.08.010. Your doctor can This site needs JavaScript to work properly. 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. Causes of acute and chronic kidney failure include medications, cancer, and cirrhosis. NLM if the death rate in quartile one is 20% and in quartile 4 is 40% then the mortality ratio is 2.0. Despite extensive research, scientists have not yet been able to identify the exact reasons that contribute to an increase in the alkaline phosphatase levels. Note – convention says that a P value of 0.05 (1 in 20) or less is “statistically significant” – this means only a 1 in 20 chance of being a fluke finding. 2013 Jun;106(6):505-15. doi: 10.1093/qjmed/hct051. Studies have shown that raised albuminuria, even without overt renal function decline, is associated with elevated  B12 3. Measuring holotranscobalamin II, an early indicator of negative vitamin B12 balance, by radioimmunoassay in patients with ischemic cerebrovascular disease. They state they did this “to improve the graphic presentation of the Hazard Ratios.”. Regression analysis revealed that the moderate … No one cause of death emerged. Koyama K et al. Long-term complications can include growth delay, intellectual disability , kidney disease , and pancreatitis . In this case the results suggests that the probability of the finding of difference between quartile 1 and 4 being a coincidence is 1 in a 1000 – which on the face of it seems pretty clear cut. B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease. However, the chance of winning the lottery with one ticket is 1 in 45,057,474 i.e. 2020 Jul 22;9(8):2326. doi: 10.3390/jcm9082326. Institute of Medicine. There are a few different ways to treat anemia in chronic kidney disease, including iron supplementation, erythropoietin, red blood cell transfusion and vitamin B12 and folic acid supplements. The confidence interval is a statistical calculation which indicates whether a result is simply considered a chance finding –  in this context it the confidence interval is less than 1.0 then we consider this result to be likely by chance alone  – hence the results between quartiles 2/3 and quartile 1 is considered to be by chance. If you have kidney disease ask your doctor which tests you will have and how often they will be done. 1, Auce A.  |  10 (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.). 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. The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study. Methylmalonic acid (MMA) is best known for its use as a functional marker of vitamin B12 deficiency. Abnormal cyanide metabolism in uraemic patients. Nephrol Dial Transplant. 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 – dementia, vascular disease, neurological disease, mental health disorders etc. Whether something has been brewing as the cause of my high b12 I have yet to find out. The thyroid becomes damaged and can’t make enough thyroid hormones. The mechanism being white blood cells (granulocytes) releasing B12 binding proteins. The only reason I can think for this claim would be to try to increase the number of people picking up the study rather than it remaining in some more obscure specialist journal. Elevated levels of serum cobalamin may be a sign of a serious, even life-threatening, disease. 6 Plausibility – this is easy to understand – when we observe smoking and lung cancer together it is plausible that one causes the other. Are your vital B12 injections being stopped? If we screen the population for yellow stained fingers then we will find a correlation with an increased risk of lung cancer. To explain this it is useful to consider playing the lottery – in this case winning  is a benefit not a risk (at least in theory… ). 2, Lejniece S. 3 1 E. Gulbis Laboratory, Riga LV-1006, Latvia; 2 University of Latvia, Riga LV-1586, Latvia; 3 Riga Stradins University, Riga LV-1007, Latvia; Summary. Cyanide metabolism is abnormal in individuals with CKD due to decreased clearance [ 20 ]. Is there a mechanism by which high B12 levels might be a cause of harm? This is why Hill and Doll reported that smoking caused lung cancer, not just that they were associated. People who develop chronic kidney disease may have some or all of the following tests and measurements. 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 who’s level is less than 338.85. disease, adverse drug reactions, acute kidney injury and prolonged hospital admissions. Cellular Uptake of Cobalamin: Transcobalamin and the TCblR/CD320 Receptor Edward V. Quadros et al Biochimie. In 2000 David moved into family general practice and was a GP partner for many years. Lonn E et al. I have 1 kidney and my creatinine is .75 which is great. Hypercobalaminemia can yield clinical signs indicating functional and qualitative vitamin B12 deficiency. Please enable it to take advantage of the complete set of features! This study has been following about 4500 men for 14 years. 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]. This review reflects the potential importance of the vitamin B12 assay as an early diagnostic marker of these diseases. 7 Coherence – does the association fit with other facts? 2014 Apr 1; 9(2): e76–e83. 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. Kidney disease is when your kidneys are damaged in some way and are not filtering your blood effectively. Background—Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. I have 1 kidney and my creatinine is .75 which is great. 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. So is there a plausible mechanism by which high B12 levels might be a cause of harm? I think this has been sufficient to “set the hares running” by those with vested interests against any supplementation recommendation. doi: 10.1136/bmjopen-2020-038990. As per “consistency” there have been numerous studies of B12 supplementation that have not shown increased mortality 4,5 . 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 – we cannot determine the actual percentage of the final 8,592 but it is unlikely to be less.) In the other solid tumours the mechanism is believed to be both the secretion of binding proteins and also stimulation of white cell overproduction, as below. [The significance of an elevated cobalamin concentration in the blood]. 1. 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 Kidney disease, or diabetic nephropathy, develops progressively in patients with type 2 diabetes. Epub 2011 Oct 22. 2020 Jul 23;26:e923828. They also corrected for various laboratory measurements and blood pressure etc.  It’s easy, just post your questions, comments or feedback below. Receiving a Diagnosis of Pernicious Anemia: Exploring Experiences of Relationships With Health Professionals. High levels of Vitamin B12 may be too much of a good thing. 4 Temporality – perhaps best called “direction of causation.” With an association – which is the cart and which is the horse? Malignant blood diseases including for example chronic myeloid leukaemia, the acute leukaemias and other myeloproliferative diseases all elevate B12. Another important consideration is the possibility that elevated B12 levels and B12 supplementation may be harmful in individuals with CKD. 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. Vitamin B-6 (pyridoxine) is important for normal brain development and for keeping the nervous system and immune system healthy.Food sources of vitamin B-6 include poultry, fish, potatoes, chickpeas and bananas. Hence we see the polemic statements “high B12 levels nearly double your death rate.”. Definition. Early development of kidney disease is assessed by … Background: Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Kidney disease is called a ‘silent disease’ as there are often few or no symptoms. Homocysteine lowering with folic acid and B vitamins in vascular disease. ranked all the participants according to their B12 level and then split them into four groups – the lowest quarter of B12 levels, 26-50 % level , 51 -75 % and 76-100%. 2 Consistency – do we find the association in different people, in different circumstances at different times? It has always struck me as an absurdity that this artefactual compound has been used for the next 80 years as a supplement –in the UK NHS this is the only prescribable oral form, in the USA it is commonly used as an injectable form, and of course it is the form found in the majority of purchased supplements. Clinically, it can be paradoxically accompanied by signs of deficiency, reflecting a functional deficiency linked to qualitative abnormalities, which are related to defects in tissue uptake and action of vitamin B12. As I discuss later very high levels of B12 are caused by a number of serious diseases, not vice versa. I cant help wondering if it was a good idea to have reinstated the b12 as I have never felt so Ill or Following a balanced diet is the preferred way to get the recommended amount of these vitamins, however people with chronic kidney disease (CKD) often cannot get all the recommended vitamins for varying health reasons. Cyanocobalamin is an artificial compound of B12 created by the reagents used in X-ray crystallography in the 1940’s when the structure of B12 was first established. It stand to reason that these individuals are at higher risk of several diseases due to their functional B12 deficiency despite elevated serum levels. 2. 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 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. Association of elevated vitamin B 12 with oncohematological diseases in a cohort of 79,524 patients from Latvia. 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. Epub 2013 Feb 27. However, MMA concentrations not only depend on adequate vitamin B12 status, but also relate to renal function and endogenous production of propionic acid. There are 5 stages of chronic kidney disease. 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 1  – I can think of no biological reason why this should be so. 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%  (just over 5/100)  – 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%. High vitamin B12 levels could also be explained by elevated vitamin B12 binding protein levels that are not filtered properly by the kidneys. In fact, you can lose up to 90 per cent of your kidneys’ functionality before experiencing any symptoms. Serum Creatinine: Creatinine is a waste product in your blood that comes … Plasma Homocysteine, but Not Folate or Vitamin B-12, Predicts Mortality in Older People in the United Kingdom Alan D. Dangour et al The Journal of Nutrition, Volume 138, Issue 6, June 2008, Pages 1121–1128. 40,856 subjects (47.8%) responded – 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. 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.  In the discussion they acknowledge “the underlying mechanism of the association of plasma concentration of Vitamin B12 with mortality is incompletely understood” but then go on to say “The results of this study could also be clinically interpreted in the context of oral vitamin B12 supplementation.”. Meyer HE et al JAMA Netw Open. 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. This is the best way to assess kidney function. HHS The proportion of the population affected by a number of different genetic changes is currently unclear but probably runs at least around 1-2% so is not uncommon7. In summary this study does not in fact meet any of the Braford Hill criteria that would suggest causation rather than association. A codified approach is needed to determine the potential indications of a search for high serum cobalamin and the practical clinical strategy to adopt upon discovery of elevated cobalamin levels. We explain below why this study doesn’t provide enough evidence for us to change our B12 guidelines. In primary liver cancer the odds ratio is 4.7 and for cancers with liver metastases the odd ratio is as high as 6.2 – this is consistent very strongly with causation. The relative “risk” of winning the lottery if you buy two lottery tickets instead of one is 100% higher or 2.0 times more likely. The title of the study is the “Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands” 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. If you have chronic kidney disease, you and your doctor will manage it together. USA.gov. Kidney Disease Diagnosis. In other words, the high B12 levels may have been caused by the body not being able to process B12 properly due to a liver or kidney disease—not due to a high B12 intake. Findings from intervention trials support this conclusions. 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. My apologies for some of the technicalities that I will use but this is necessary in this context. But upon following up years later, a previously reported elevated B12 was not associated with a future diagnosis of either condition ( McMahon, 2015 ). Some studies have indicated that elevated serum levels of vitamin B12 might be a sign of a serious and life-threatening disease. age, sex or smoking and also any other diseases. This was a “post hoc longitudinal cohort study” which simply means that the authors looked back at a population they had studied, split the population into groups (cohorts) and performed an analysis  -in this case B12 levels and overall mortality. The first paper simply showed no benefit of using Vitamin B supplementation (not just B12) on the progression of coronary heart disease. 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. For example we were advised for many years that HRT was a good protector for heart disease because women on HRT, in the largest observational study at the time, had less heart disease – many years on further analysis indicated that this was because healthier women were more likely to seek HRT and if anything once this was corrected for there was an increase in heart disease form taking HRT. Persons with low B12 levels were excluded together with … The ratio of death rates is called the “Hazard Ratio.”, 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. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Studies have shown that raised albuminuria, even without overt renal function decline, is associated with elevated B12 3. For example, we have seen evidence that some drugs are associated with birth defects, so if we see an association between a new drug and birth defects we can see an analogy. Most of it gets flushed out in the urine; the rest is absorbed in the liver, kidneys and muscle tissues. 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 “this paper adds to the growing body warning people that vitamin supplements may not have as much benefit as they claim.” Insider Health leads with the headline “High levels of B12 were associated with an increased risk of early death in a new study” and the web page address for this article is actually titled “B12 supplements could be lethal in high doses, study finds.”. As there are often few or no symptoms got blood work back that states everything is pretty much normal vascular. 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