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Vitamin B12-mangel, artikkel av Sally Pacholok        (oversatt versjon)

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DECEMBER 13, 2013 Sally M. Pacholok, RN, BSN

Det er svært viktig å identifisere vitamin B12-mangel (kobalamin) hos pasienter tidlig. Kobalamin (vitamin B12) mangel har i stor grad blitt ignorert i mange tiår av leger og medlemmer av helsepersonell. Så, nøyaktig hvor mange pasienter som har en udiagnostisert B12-mangel i USA i dag, og hvorfor skal apotekerne bry seg om det? Nåværende litteratur rapporterer at B12-mangel rammer 16% av befolkningen, eller 48 millioner amerikanere. 1 Andre rapporterer  at det kan være så mye som 25% 

Framinghams, les mer, trykk her:  studier fant at nesten 40% av befolkningen i alderen 26 til 83 år hadde B12 nivåer som befant seg i "lav-normal" området - et nivå hvor mange begynner å oppleve nevrologiske symptomer. Dette er problematisk fordi lav B12 forårsaker en rekke nevrologiske og psykiatriske manifestasjoner. B12 mangel har blitt underbehandlet i helsevesenet og i stor grad ignorert til fordel for mer anerkjente og dyrere  behandlingsdiagnoser. Dette har resultert i feilbehandling, rasultatet er at millioner av mennesker sliter med store helseplager.

Tidlig diagnose og behandling er meget viktig da B12-mangel treffer alle aldre, og begge kjønn. Det er uten tvil den vanligste næringsdefekten som forårsaker skade i USA. Tidlig diagnose og behandling er kritisk for å forhindre nevrologisk skade, funksjonshemning, dårlige resultater og tidlig død. B12-mangel forårsaker demyeliniserende nervesystems sykdom, demens, psykiatrisk sykdom, anemi, vaskulær okklusjon, fallrelatert traume, undertrykt immunsystem og beinmargsfeil.

Vitamin B12 er et vannoppløselig vitamin syntetisert av mikroorganismer og finnes i spormengder i matvarer av animalsk opprinnelse.

Det er avgjørende for DNA-syntese, metylering, folatmetabolisme, erytropoiese, nevrodevelopment og funksjon av nervesystemet. B12 fungerer som en koaktor for metioninsyntase og L-metylmalonyl-CoA-mutase. En mangel forårsaker dermed forhøyet homocystein og metylmalonsyre. Opptaket avhenger av gastrisk parietale celler som utskiller saltsyre, egenvekt og pepsin. Bukspyttkjertelenzymer og reseptorer i distal ileum må være tilstede sammen med blodprotein-transkobalamin II for å utnytte B12. Til slutt konverterer leveren B12 til de aktive former adenosylcobalamin og metylcobalamin for utnyttelse.

Fordi B12 må følge en kompleks vei av flere trinn for riktig absorpsjon og assimilering, er det mange årsaker til mangel. Disse inkluderer malabsorbsjonssyndrom, autoimmun sykdom, diett, legemidler, kjemoterapi, stråling, spiseforstyrrelser, Helicobacter pylori, gastrointestinale operasjoner, nitrogenoksid, leversykdom og genetiske defekter. Andre risikogrupper inkluderer veganer, vegetarianere, alkoholikere og personer med Crohns sykdom, bakteriell overvekst i små tarmar, celiac sykdom, gastrisk bypass og AIDS.

Opptil 30% av de eldre voksne har atrofisk gastritt med hypoklorhydria som hemmer utløpet av diettproteinbundet B12 som forårsaker mangel.

Tilsvarende vil kronisk bruk av legemidler som reduserer magesyre, som protonpumpehemmere, H2-blokkere og antacida, forårsake lav B12. Medikamenter som metformin, kolchicin, kalium, kolestyramin, neomycin, kloramfenikol og para-aminosalicylsyre påvirker også B12 absorpsjon.

Ubehandlet B12-mangel kan forårsake vaskulær sykdom, inkludert slag, myokardinfarkt, lungeemboli og dyp venetrombose, fordi denne mangelen forårsaker hyperhomocystinemi. B12 er kofaktoren for omdannelse av homocystein til metionin. Overflødig homocystein forårsaker at blodårene mister deres elastisitet, noe som gjør det vanskeligere for dem å utvide seg. Dette gjør at kolesterol, kollagen og kalsium bygger seg  opp, noe som  igjen forårsaker plakkdannelse.

Kort- og langsiktige konsekvenser er enorme. Ubehandlet B12-mangel forårsaker balanseproblemer, parestesier, svakhet, svimmelhet, postural hypotensjon og synsforstyrrelser. Disse symptomene øker risikoen for fall dramatisk, noe som igjen fører til traumer (dvs. frakturer, subdale hematomer), sykehusopphold, tap av selvstendighet, -  pleiehjem og tidlig død.

B12-mangelepidemien er frustrerende fordi velutdannet helsepersonell overser en lett diagnostisert tilstand som er billig å behandle. Ikke bare forårsaker B12-mangel alvorlig nevrologisk sykdom, men forårsaker også kronisk anemi, som i motsetning til det man ofte tror, er ofte ikke makrocytisk. 28

Medisinene er ofte reseptbelagte som  (Procrit og Epogen). Ubehandlet B12-mangel kan forårsake hypercellulær og dysplastisk benmarg, som kan forveksles med tegn på akutt leukemi. I akuttavdelingen (ED) diagnostiserer vi rutinemessig B12-mangel hos pasienter som presenterer generell svakhet, anemi, kortpustethet, nevropati, vanskeligheter med ambulering, endringer i mental status, psykisk sykdom og fallrelatert traume.

Diagnostiseringen B12-mangel i akuttmottaket, indikerer at disse pasientene ikke  får hjelp i primærhelsetjenestene, og at spesialister ikke klarte å inkludere B12-mangel i differensialdiagnosen av pasientenes klager eller  kanskje legger  skylden på  "normal aldring". 

Mange mennesker i alle aldre som lider av alvorlig angst, depresjon og en rekke andre psykiatriske lidelser foreskrives farlige og kostbare psykotrope stoffer, narkotika eller benzodiazepiner når det underliggende problemet faktisk kan være B12-mangel.

På samme måte kan barn diagnostisert på autismespektret og foreskrevne psykiatriske medisiner ha adferds- og nevrologiske manifestasjoner på grunn av lav B12.

Utviklingsforsinkelse og mental retardasjon forårsaket av B12-mangel er godt dokumentert. 36-40 Spedbarn får ofte B12-mangel på grunn av deres mors udiagnostiserte B-mangel under graviditet og amming. 

Hver farmakolog trenger å være oppmerksom på den nevrologiske konsekvensen av B12-mangel, og hvordan den kan maskeres som psykisk lidelse, multippel sklerose, Parkinsons, demens / Alzheimers, anfallssvikt, autisme og andre nevrologiske lidelser.

Hvis pasienten har B12-mangel, kan injiserbar hydroksokobalamin være den mest pålitelige medisinen, spesielt hvis nevrologiske symptomer er tilstede. Hydroxokobalamin bør erstatte cyanokobalamininjeksjoner på grunn av forbedret retensjon, større tilgjengelighet til celler og ikke behov for dekyanering.  Hydroksokobalamin koster ikke mer enn cyanokobalamin, og den er lett tilgjengelig i USA (distribuert av Watson Pharmaceuticals, Inc). Hydroxokobalamin brukes til spedbarn og barn med medfødt feil i B12-metabolisme og er den foretrukne form til bruk hos røykere og pasienter med lever- og nyresvikt.

 High-dose, sublingual eller MicroLingual B12 tabletter (2000 mcg eller høyere) er det nest beste alternativet og er en effektiv tilnærming for enkelte pasienter. Tabletter og kapsler inneholder mange bindemidler og fyllstoffer, noe som vanskeliggjør riktig opptak. Centrene for Medicare & Medicaid Services gjør tiltak for å forbedre kvaliteten på omsorg på sykehus og redusere antallet "aldri hendelser" -forventelige medisinske feil som medfører alvorlige konsekvenser for pasienten. Udiagnostisert og ubehandlet B12-mangel er en ukjent forebyggbar medisinsk feil som må behandles og elimineres. Apotekere er viktige helsepersonell og er nødvendig for å spre B12 bevissthet til både pasienter og leger.


Recognizing vitamin B12 (cobalamin) deficiencies in patients early on is key.

Recognizing vitamin B12 (cobalamin) deficiencies in patients early on is key.

Cobalamin (vitamin B12) deficiency has been largely ignored for many decades by physicians and members of the health care team. So, exactly how many patients have an undiagnosed B12 deficiency in the United States today and why should pharmacists take note?

Current literature reports that B12 deficiency strikes 16% of the population, or 48 million Americans.1 Others report the prevalence to be as high as 25%.2 The Framingham Offspring Study found that nearly 40% of people aged 26 to 83 years had B12 levels in the "low normal" range-a level at which many begin experiencing neurological symptoms. This is problematic because low B12 causes an array of neurologic and psychiatric manifestations. B12 deficiency has been severely underplayed in health care and largely ignored in favor of more recognized and more expensive-to-treat diagnoses. This has resulted in both substandard care and malpractice, costing millions of individuals their health and wasting billions of health care dollars.

Early Diagnosis and Treatment Are Critical

B12 deficiency strikes all ages, races, economic classes, and both sexes. It is arguably the most common nutritional deficiency causing injury in the United States. Early diagnosis and treatment is critical to prevent neurologic injury, disability, poor outcomes, and premature death. B12 deficiency causes demyelinating nervous system disease, dementia, psychiatric illness, anemia, vascular occlusions, fall-related trauma, suppressed immune system, and bone marrow failure.3

Vitamin B12 is a water-soluable vitamin synthesized by microorganisms and detected in trace amounts in foods of animal origin.4 It is crucial for DNA synthesis, methylation, folate metabolism, erythropoiesis, neurodevelopment, and nervous system function. B12 functions as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase. A deficiency thereby causes elevated homocysteine and methylmalonic acid. Uptake depends on gastric parietal cells excreting hydrochloric acid, intrinsic factor, and pepsin. Pancreatic enzymes and receptors in the distal ileum must be present along with the blood protein transcobalamin II to process B12. Lastly, the liver converts B12 to the active forms adenosylcobalaminand methylcobalamin for utililzation.5,6

Because B12 must follow a complex pathway of several steps for proper absorption and assimilation, there are numerous causes of deficiency. These include malabsorption syndromes, autoimmune disease, diet, drugs, chemotherapy, radiation, eating disorders, Helicobacter pylori, gastrointestinal surgeries, nitrous oxide, hepatic disease, and genetic defects. Other groups at risk include vegans, vegetarians, alcoholics, and individuals with Crohn's disease, small bowel bacterial overgrowth, celiac disease, gastric bypass, and AIDS.7,8

Up to 30% of older adults have atrophic gastritis with hypochlorhydria inhibiting the release dietary protein-bound B12causing deficiency.9-12 Similarly, chronic use of drugs that decrease gastric acid, such as proton pump inhibitors, H2-blockers, and antacids will cause low B12.13-17 Medications such as metformin, colchicine, potassium, cholestyramine, neomycin, chloramphenicol, and para-aminosalicylic acid also interfere with B12 absorption.18-20

Untreated B12 deficiency can cause vascular disease, including stroke, myocardial infarction, pulmonary embolism, and deep vein thrombosis, because this deficiency causes hyperhomocystinemia. B12 is the cofactor for the conversion of homocysteine into methionine. Excess homocysteine causes blood vessels to lose their elasticity, making it harder for them to dilate and damaging their inner lining. That damage, in turn, allows cholesterol, collagen, and calcium to build up, causing plaque formation.21-27

The short- and long-term ramifications are enormous. Untreated B12 deficiency causes balance problems, paresthesias, weakness, dizziness, postural hypotension, and visual disturbances. These symptoms dramatically increase the risk of falls, which, in turn, lead to trauma (ie, fractures, subdural hematomas), hospital stays, loss of independence, nursing home placement, and premature death.

The B12 Deficiency Epidemic

The B12 deficiency epidemic is frustrating because well-educated health care providers overlook such an easily diagnosed and inexpensively treated condition. Not only does B12 deficiency cause severe neurologic disease, but it also causes chronic anemia, which contrary to popular belief is frequently not macrocytic.28 Often, prescription drugs such as epoetin alfa (Procrit and Epogen) are prescribed. Untreated B12 deficiency can cause hypercellular and dysplastic bone marrow, which can be mistaken for signs of acute leukemia.

In the emergency department (ED), we routinely diagnose B12 deficiency in patients presenting with generalized weakness, anemia, shortness of breath, neuropathy, difficulty ambulating, mental status changes, mental illness, and fall-related trauma. Diagnosing B12 deficiency in the ED indicates that these patients' primary care physicians and other specialists failed to include B12 deficiency in the differential diagnosis of their complaints or perhaps blamed their conditions on "normal aging."

Many people of all ages suffering from severe anxiety, depression, and a host of other psychiatric disorders are prescribed dangerous and costly psychotropic drugs, narcotics, or benzodiazepines when the underlying problem actually may be B12deficiency.29-35

Similarly, children diagnosed on the autism spectrum and prescribed psychiatric medications may have behavioral and neurologic manifestations because of low B12. Developmental delay and mental retardation caused by B12 deficiency is well documented.36-40 Infants often become B12 deficient because of their mother's undiagnosed B deficiency during pregnancy and breast-feeding.

Every pharmacist needs to be aware of the neurologic consequence of B12 deficiency and how it can masquerade as mental illness, multiple sclerosis, Parkinson's, dementia/Alzheimer's, seizure disorders, autism, and other neurological disorders.41-47

If your patient has a B12 deficiency, injectable hydroxocobalamin is the most dependable medication, especially if neurologic symptoms are present. Hydroxocobalamin should replace cyanocobalamin injections because of improved retention, greater availability to cells, and no need for decyanation. Largely unknown, hydroxocobalamin does not cost more than cyanocobalamin, and it is readily available in the United States (distributed by Watson Pharmaceuticals, Inc). Hydroxocobalamin is the form used in infants and children with inborn errors of B12 metabolism and is the preferred form for use in smokers and patients with hepatic and renal disorders.48-51

High-dose, sublingual, or MicroLingual B12 tablets (2000 mcg or greater) are the next best alternative and are an effective approach for some patients. Compressed tablets and capsules contain many binders and fillers, making proper absorption difficult.

The Centers for Medicare & Medicaid Services is taking several actions to improve the quality of care in hospitals and reduce the number of "never events"-preventable medical errors that result in serious consequences for the patient. Undiagnosed and untreated B12 deficiency is an unrecognized preventable medical error that needs to be addressed and eliminated. Pharmacists are vital members of the health care team and are needed to spread B12 awareness to both patients and physicians.

Sally Pacholok has been researching cobalamin (vitamin B12) deficiency and practicing emergency nursing for 26 years. She is a frequent radio guest on nationally syndicated talk shows, lecturer, media personality, and co-author of Could It Be B12? An Epidemic of Misdiagnoses (2nd edition, 2011)-the winner of the Indie Excellence Award for best health book.Could It Be B12? has been translated into Dutch and Slovenian, and is now being published in India as well. Pacholok's book was made into a documentary in 2012, and a screenplay has been completed to be made into a movie regarding Pacholok's lifelong battle to improve the country's health care system and expose substandard care. Pacholok is working with other countries to improve early diagnosis and treatment worldwide. She aspires to get September designated as B12 Awareness Month. Pacholok is also an educator and public speaker for Superior Source Vitamins. Visit www.B12Awareness.org.

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