Losec (Omeprozole), side effects and Vitamin B12 Deficiency

Losec is the most prescribed proton pump inhibitor for adults and children alike. Proton-pump inhibitors are the single most costly medicine expense in New Zealand. It is prescribed for the treatment of reflux oesophagitis, duodenal ulcers, peptic ulcers, hiatus hernia, NSAID-associated gastric and duodenal ulcers or erosions, acid related dyspepsia and Zollinger-Ellison syndrome.  Just recently in New Zealand Losec can be purchased over the counter in pharmacies.

It is little wonder then that there are so many individuals with poor digestion and associated conditions. In the stomach, gastric enzymes denature proteins, which release vitamin B12 (among others). The gastric parietal cells produce acid and intrinsic factor; the intrinsic factor becomes a B12 binding protein when the gastric pH reaches 8.  A 20mg dose of Losec daily maintains an intragastric pH greater than 3 and because protein digestion requires a pH closer to 1, Losec users have a reduced protein digestion and B12 release.

Prolonged acid inhibition by proton pump inhibitors could promote vitamin B12 malabsorption in two possible ways. Firstly, an increased gastric pH could impair the body’s ability to extract vitamin B12 from the dietary proteins to which it is bound. Some studies confirmed that proton pump inhibitors reduce the absorption of protein-bound cobalamin. Secondly, in theory, reduced acidity could promote bacterial overgrowth in the proximal small intestine, which could increase bacterial consumption of this nutrient. It is probable that by inhibiting parietal cell function intrinsic factor secretion is also reduced.

The mechanism of Losec is in the binding of its active form within the parietal cells of the gastric mucosa with H+, K+-ATPase. This enzyme is responsible for the pumping of protons (proton pump) into the gastric lumen in exchange for potassium ions. Losec leads to a dose dependent inhibition (about 90%) of stomach acid secretion from the histamine, gastrin and acetylcholine dependant pathways. This leads to concerns of long-term use and decreased protein metabolism and a deficiency of vitamin B12 due to its protein bound form and its reliance on hydrochloric acid for release. There are other digestive processes which are reliant on hydrochloric acid for absorption and or utilization, eg: non-heme iron, folic acid, vitamin D, calcium, ascorbic acid, beta-carotene, magnesium (oxide) and zinc. Hydrochloric acids function is not only for the digestion and absorption of proteins, it encourages the flow of bile, it activates pepsin from pepsinogen and protects against pathogens, which may have been ingested.

Losec is completely metabolised by the cytochrome P450 system (CYP), mainly in the liver. The major part of its metabolism is dependent on the polymorphically expressed, specific isoform CYP2C19 (S-mephenytoin hydroxylase), responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. In accordance with this, as a consequence of competitive inhibition, there is a potential for metabolic drug-drug interactions between Losec and other substrates for CYP2C19, for example it may prolong the elimination of diazepam, warfarin (increases in INR and prothrombin time) and phenytoin, by inhibiting oxidative metabolism on which they are dependant.

There have been clinical reports of interactions with other drugs metabolised via the cytochrome P450 system (e.g. cyclosporine, disulfiram, benzodiazepines, Digoxin, diazepam, alprazolam, lorazepam, temazepam, clorazepate, chlordiazepoxide, theophylline, Nizoral, ampicillin). Because of its long lasting inhibition of gastric secretion, it is theoretically possible that Losec may interfere with absorption of drugs where gastric pH is an important factor of their bioavailability (e.g. ketoconazole, ampicillin esters, and iron salts).

During long-term use gastric glandular cysts have been reported with increased frequency. These changes are a physiological consequence of pronounced inhibition of acid secretion; they appear to be benign and reversible. Decreased gastric acidity due to any means including proton pump inhibitors increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may lead to a slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter. Other possible health implications of the long term use of Losec for dyspepsia are an increase in gastric carcinoid tumours, a risk of atrophy of the stomach lining because of the long-term suppression of acid secretion by stomach cells, atrophic gastritis and gastric cancer. Atrophic gastritis with intestinal metaplasia may be associated with gastric adenocarcinoma.

There are many side effects related with the use of Losec, interestingly several of them could also be related to a B12 deficiency. The most common are headache, diarrhoea, constipation, abdominal pain, nausea/vomiting, flatulence, dizziness, paraesthesia, insomnia, vertigo, rash and/or pruritus, urticaria, malaise, increased liver enzymes, reversible mental confusion, agitation, aggression and depression. Less common but relevant all the same, gynaecomastia, dry mouth, stomatitis and gastrointestinal candidiasis, leukopenia, thrombocytopenia, agranulocytosis and pancytopenia, encephalopathy in patients with pre-existing severe liver disease, hepatitis with or without jaundice, hepatic failure, arthralgia, muscular weakness and myalgia, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), alopecia, hypersensitivity reactions, e.g. angioedema, fever, bronchospasm, interstitial nephritis and anaphylactic shock, increased sweating, peripheral oedema, blurred vision, taste disturbance and hyponatraemia.

If you require a natural alternative please contact Carolyn at Monarch Natural Health as there are always options.

Carolyn is not currently practicing

Written by Carolyn Fletcher (formerly McSweeney).  Carolyn is a Clinical Medical Herbalist, Clinical Nutritionist, Neuro-linguistic Programming (NLP) Master Practitioner, HNLP Coach/Counsellor, Live Blood Analysist and has a National Certificate in Adult Education and Training.