Are serum homocysteine levels increased in patients using proton pump inhibitors?

Öz

Background and Aim: DNA synthesis, which is required for cell division and proliferation, is provided by transformation of homocysteine to methionine. Vitamin B12 is the cofactor of methionine synthesis that plays a role in this reaction. vitamin B12 deficiency causes the accumulation of homocysteine. Hyperhomocysteinemia has been associated with arteriosclerosis and cerebral embolism. Proton pump inhibitors are widely used drugs that inhibit H+/K+-ATPase, which is found in parietal cells. Because HCl is required for separation of vitamin B12 from food, the ingestion of proton pump inhibitors can cause vitamin B12 deficiency, which can lead to hyperhomocysteinemia. In our study, we investigated the effect of the use of proton pump inhibitors on vitamin B12 and serum homocysteine levels. Material and Methods: In this study, 44 patients who had been using proton pump inhibitorsfor at least 3 months because of various indications and 38 patients (control group) who had never used proton pump inhibitors who admitted to our outpatient clinic between March and July 2009 were included. The ages of the patients and the control group, serum levels of homocysteine, vitamin B12 and folic acid, mean corpuscular volume (MCV) values, and duration of proton pump inhibitors use were recorded. In addition, among the patients on proton pump inhibitors, the fasting serum levels of homocysteine, vitamin B12 and folic acid and MCV values were compared between patients using proton pump inhibitors for less than 2 years or more than 2 years. Results: The average duration of proton pump inhibitors use was 19.5 months in the patient group. There was no significant difference between patients and controls in mean age (in patient group: 39±14, in control group: 41±5; p=0.7) and gender (patient group: 19 men, 25 women, control group: 13 men, 25 women; p=0.4). No significant difference was detected between patient and control groups when comparing in terms of homocysteine (patients: 9.98±4.79, controls: 9.40±0.527; p=0.5), VB12 (patients: 328±305, controls: 264±105; p=0.2), folic acid (patients: 9.20±3.20, controls: 8.91±2.94; p=0.7), and MCV (patients: 83±11, controls: 86±8; p=0.1). There were no differences between homocysteine, vitamin B12, folic acid and MCV levels when the patients were compared among themselves regarding the use of proton pump inhibitorsfor more or less than 2 years. Conclusion: According to our study, long-term use of proton pump inhibitors showed no significant effect on the levels of vitamin B12 and consequently on the level of homocysteine. For this reason, we can say that these patients do not have greater cardiovascular risks caused by hyperhomocysteinemia with respect to the general population.

Anahtar Kelimeler

• Homocysteine, vitamin B12, proton pump inhibitors

Proton pompası kullanan hastalarda serum homosistein seviyesi artmış mıdır?

Öz

Giriş ve Amaç: Hücre bölünmesi ve çoğalması için gerekli olan DNA sentezi homosisteinin metionine dönüşmesiyle sağlanmaktadır. Vitamin B12 bu reaksiyonda rol alan metionin sentetazın kofaktörüdür. Vitamin B12 eksikliğinde homosistein birikimi olur. Hiperhomosisteinemi ise arterioskleroz ve serebral tromboemboli ile ilişkili bulunmuştur. Proton pompa inhibitörleri yaygın olarak kullanılan ilaçlardır. Bu ilaçlar paryetal hücrelerdeki proton pompasında bulunan H+/K+-ATPazı inhibe ederek HCl'yi inhibe ederler. Vitamin B12'nin gıdalardan ayrılmasında HCl gerektiğinden, proton pompa inhibitörü kullanımı vitamin B12 eksikliğine bu da hiperhomosisteinemiye yol açabilir. Çalışmamızda proton pompa inhibitörü kullanımının vitamin B12 ve homosistein düzeyine etkisini araştırdık. Gereç ve Yöntem: Çalışmaya Mart ve Temmuz 2009 arasında polikliniğimize başvuran ve çeşitli nedenlerle en az üç aydır proton pompa inhibitörü kullanan 44 (hasta grubu) ve daha önce hiç proton pompa inhibitörü kullanmamış 38 hasta (kontrol grubu) alındı. Hasta ve kontrol grubunun yaşı, serum homosistein düzeyi, vitamin B12, folik asit ve MCV değerleri ve hastaların proton pompa inhibitörü kullanım süresi kaydedildi. Ayrıca proton pompa inhibitörü kullanan hastalar kendi arasında, 2 yıldan az ve fazla proton pompa inhibitörü kullananlar olarak açlık serum homosistein düzeyi, vitamin B12 vitamini, folik asit ve MCV değerleri açısından karşılaştırıldı. Bulgular: Hasta grubunda proton pompa inhibitörü kullanım süresi ortalama 19.5 ay idi. Hasta ve kontroller arasında yaş (hasta grubu 39±14, kontrol grubu 41±5 p=0,7) ve cinsiyet (hasta grubunda19 erkek, 25 kadın; kontrol grubunda 13 erkek, 25 kadın p=0,4) açısından anlamlı bir fark yoktu. Hasta ve kontroller homosistein (hasta 9.98±4.79 kontrol 9.40±0.527 p=0.5), B12 vitamini (hasta 328±305 kontrol 264±105 p=0.2), folik asit (hasta grubunda 9.20±3.20 kontrol grubunda 8.91±2.94 p=0.7) ve MCV (hasta 83±11 kontrol 86±8 p=0.1) yönünden karşılaştırıldığında iki grup arasında anlamlı bir fark saptanmadı. Hasta grubu kendi arasında 2 yıldan az ve fazla proton pompa inhibitörü kullananlar şeklinde karşılaştırıldığında homosistein düzeyi, vitamin B12, folik asit ve MCV değerleri açısından anlamlı bir fark saptanmadı. Sonuç: Çalışmamıza göre, uzun süreli proton pompa inhibitörü kullanımının vitamin B12 ve buna bağlı olarak homosistein düzeyi üzerinde anlamlı bir etkisinin olmadığı ve bu sebeple bu hastaların hiperhomosisteineminin getirdiği kardiyovasküler risklere genel toplumdan daha fazla sahip olmadığı söylenebilir.

Anahtar Kelimeler

• Homosistein, vitamin B12, proton pompa inhibitörleri

Kaynakça

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