Vitamin B12 deficiency--a major cause of megaloblastic anaemia in patients attending a tertiary care hospital

BACKGROUND: Folate and vitamin B12 deficiencies have been known to cause megaloblastic anaemia. Since the deficiencies of these two vitamins are very common in Pakistani population, it would be imperative to investigate their role in causing megaloblastic anaemia. The objective of this study was to find out the contribution of folate and vitamin B12 deficiencies in causing megaloblastic anaemia in our patient population. METHODS: In this retrospective cohort study, clinical records of 220 patients (101 females and 119 males with an age range of 1-80 years) who presented themselves with macrocytic anaemia at the Aga Khan University Hospital were collected. Data pertaining to complete blood count and serum levels of folate and vitamin B12 were analysed. RESULTS: The mean haemoglobin (Hb) level was 6.8 +/- 0.2 gm/dl. Sixty-nine percent of the patients had severe anaemia (Hb \u3c 8 gm/dl). Mean +/- SEM values of haemoglobin, serum folate and serum B12 were not significantly different between males and females (Hb 6.4 +/- 0.3 gm/dl vs 6.3 +/- 0.3 gm/dl; folate 6.9 +/- 0.8 etag/ml vs 7.8 +/- 1 etag/ml; B12 259 +/- 65 rhog/ml vs 225 +/- 45 rhog/ml, respectively). Linear regression analysis showed that serum folate was inversely related with the mean corpuscular volume (MCV, p = 0.04). Spearman\u27s correlation analysis indicated an inverse mild association between MCV and serum folate (correlation coefficient = -0.18). Folate deficiency was 43.4%, while vitamin B12 deficiency was 78.5% in these patients. Seventy-one percent of folate-deficient patients had vitamin B12 deficiency as well, while 26.1% of patients with B12 deficiency had a co-occurrence of folate deficiency. CONCLUSION: Vitamin B12 deficiency appears to be the major factor leading to megaloblastic anaemia in our study population. Inadequate dietary intake, over-cooking of our food and poor absorption might be contributing to high prevalence of vitamin B12 deficiency in this population

High prevalence of vitamin D deficiency and insufficiency in a low income peri-urban community in Karachi

Objective: To determine the frequency of vitamin D deficiency and insufficiency in a low-income peri-urban population.Methods: The cross-sectional study was conducted in a low-income, unplanned settlement in Karachi, and comprised apparently healthy adults who were recruited randomly with informed consent. Serum levels of 25-hydroxy vitamin D were measured using a kit obtained from Roche Diagnostics. One-way analysis of variance and logistic regression were used for statistical analysis.Results: Of the 858 subjects, 507(59%) were females and 351(41%) males (age range: 18-60 years). Prevalence estimates of vitamin D deficiency (\u3c20ng/ml) and insufficiency (20.0-29.9ng/ml) were found to be 501(58.4%) and 269(31.4%), respectively. Odds ratio of vitamin D deficiency was significantly higher in females compared to males after adjusting for education and smoking status (p=0.001).CONCLUSIONS: High prevalence of vitamin D deficiency among females in one of the peri-urban areas points towards a public health problem which requires attention of the medical community

Trans fatty acids – A risk factor for cardiovascular disease

Trans fatty acids (TFA) are produced either by hydrogenation of unsaturated oils or by biohydrogenation in the stomach of ruminant animals. Vanaspati ghee and margarine have high contents of TFA. A number of studies have shown an association of TFA consumption and increased risk of cardiovascular disease (CVD). This increased risk is because TFA increase the ratio of LDL cholesterol to HDL cholesterol. Food and Agriculture Organization of the United Nations and World Health Organization have come up with the recommendation that the contents of TFA in human dietary fat should be reduced to less than 4%. There is high prevalence of CVD in Pakistan. High consumption of vanaspati ghee which contains 14.2-34.3% of TFA could be one of the factors for this increased burden of CVD in Pakistan. Consumption of dietary fat low in TFA would be helpful in reducing the risk of CVD in South Asia. Denmark by banning the sale of food items with TFA has brought down the number of deaths due to coronary heart disease by nearly 50% over a period of 20 years. Public awareness about the adverse effects of TFA on human health would be extremely important. Media can play a very effective role in educating the masses and advocating the policy for the sale of only low TFA food items. Literature sources: Google and US National Library of Medicine, National Institute of Health were the sources of papers cited in this review article

Hyperhomocysteinemia and coronary artery disease in Pakistan

The relative risk of developing coronary artery disease (CAD) in Pakistani men is highest in early ages. Majority of those suffering from CAD belong to the lower middle socioeconomic stratum of the society. Mild hyperhomocysteinemia (concentration of plasma homocysteine between 15-25 micromol/l) is very commonly seen in Pakistani patients with acute myocardial infarction (AMI) as well as in normal healthy subjects. There appears to be a lack of association between hyperhomocysteinemia and CAD in Pakistani population. There is also no evidence of association of methylenetetrahydrofolate reductase 677C\u3eT mutation with CAD in this population. High prevalence of deficiency of folate and vitamin B6 appears to be the major causes of hyperhomocysteinemia in Pakistani population. Deficiencies of micronutrients (folate, vitamin B6 and possibly vitamin B12) along with mild hyperhomocysteinemia, perhaps, act synergistically with other classical risk factors in Pakistani population to further increase the risk of CAD

Admission creatine kinase as a prognostic marker in acute myocardial infarction

OBJECTIVES: To investigate the prognostic significance of creatine kinase (CK) in Pakistani patients suffering from acute myocardial infarction (AMI) and to find out if CK combined with troponin T (TnT) could be a better predictor for long-term adverse cardiac event. METHODS: One hundred and eighty six consecutive patients with AMI who were eligible for streptokinase (SK) treatment were included in this prospective cohort study. The relationship between their serum/plasma CK and TnT levels at the time of admission and clinical outcome was investigated over a mean follow up of 24.12 +/- 3.75 months. RESULTS: Admission CK was found to be associated with subsequent cardiac event and mortality (P \u3c 0.01 and P \u3c 0.04 respectively). Admission CK was also mildly associated with time interval between onset of symptoms to SK treatment (correlation coefficient \u27r\u27 = 0.23). Odds of encountering a cardiac event in AMI patients with above-normal CK levels (adjusted for gender) were 3.46 times higher than the odds in patients with normal CK levels. Similarly, odds of mortality in patients with positive TnT were 4.6 times the odds in patients with negative TnT. The two biochemical markers, CK and TnT, together did not provide any further information about prognosis of the disease. CONCLUSION: Admission CK is a better prognostic marker for a subsequent cardiac event, while TnT is a better predictor of mortality over a mean follow up of nearly 2 years. Together, they do not improve predictability of an adverse cardiac event

Relationship of sociodemographic factors with serum levels of vitamin D in a healthy population of Pakistan

High prevalence of vitamin D deficiency has been reported from Pakistan. Association of sociodemographic factors with vitamin D status has received little attention in this region. Therefore, we embarked on investigating the relationship of sociodemographic factors with vitamin D levels in a healthy Pakistani population. Venous blood from 226 healthy participants (age range 19-69 years) was collected and analyzed for serum concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers. Demographic characteristics of the study participants were collected. Vitamin D deficiency (25(OH)D levels less than 20 ng/ml) was found to be 75% in this cohort. Gender, sunlight exposure and monthly household income emerged as predictors of hypovitaminosis D. Mean serum 25(OH)D levels in the groups with monthly household income less than Pakistani Rupees (PKR) 20,000, between PKR 20,000-50,000 and above PKR 50,000 were found to be 11.0±7.5, 13.9±9.6 and16.9±11.7 ng/ml, respectively. Using logistic regression the odds of having vitamin D deficiency was 3.22 (95% CI, 1.65-6.28) in the group with household income less than PKR 50,000 per month compared to the group with household income more than PKR 50,000 per month when the model was adjusted for gender and exposure to sunlight. There is an association between household income and hypovitaminosis D in a healthy Pakistani population

Smokeless Tobacco Use: A Risk Factor for Hyperhomocysteinemia in a Pakistani Population

Background Smokeless tobacco (ST) use is highly prevalent in the South Asian populations. While there have been a number of reports on association of ST consumption with cancer, very few studies have been conducted to investigate its relationship with cardiovascular disease. Hyperhomocysteinemia is a well-recognized risk factor for cardiovascular disease; however, its association with ST use has never been investigated. The objective of this study was to evaluate the relationship of ST use with hyperhomocysteinemia in an urban Pakistani population. Methodology/Principal Findings In a cross-sectional study for assessment of risks of hyperhomocysteinemia, 872 healthy adults (355 males and 517 females of age range 18–60 years) were recruited from a low-income population in Karachi, Pakistan. A detailed questionnaire was administered which included information about smoking, non-smoking, use of ST alone (chewing as well as sniffing) and use of ST with betel nuts. Fasting serum/plasma levels of homocysteine, folate, vitamin B12 and pyridoxal phosphate (PLP; a coenzymic form of vitamin B6) were analyzed. In this population, 43.4% males and 15.5% females were found to be regular users of ST products. Laborers and vendors were the major ST consumers. Smoking was not found to be associated with plasma/serum concentrations of homocysteine, folate, vitamin B12 and PLP. However, homocysteine concentrations in the group which consumed ST alone and the group which consumed ST along with betel nut were significantly higher compared to the non-user group (17.7±7.5 µmol/L, 25.48 µmol/L vs. 11.95 µmol/L, respectively; p\u3c0.01). Odds ratio for the association of hyperhomocysteinemia (\u3e15 µmol/L) was 11-fold higher in the ST-consumer group compared to the non-user group, [OR (95%CI) =11.34 (7.58–16.96); p\u3c0.001], when the model was adjusted for age, gender, folate and vitamin B12 status. Conclusion This study shows a positive association between ST consumption and hyperhomocysteinemia in a low-income urban Pakistani population

Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population

High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-beta-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age \u3c 45 years) and 153 healthy controls were genotyped for the above mentioned polymorphisms using PCR-RFLP methods. Plasma/serum samples of both patients and healthy controls were screened for homocysteine, folate and vitamin B12. One way ANOVA and chi-squared test were used for analysis of data. Mean plasma homocysteine levels in premature AMI patients and healthy controls were found to be 23±17.2 and 23±13.4 mumol/l, respectively which are higher than the upper normal limit of this biomarker (15mumol/l). MTHFR 677 CT genotype in healthy controls and MTHFR 677 TT genotype in AMI patients were found to have significantly increased levels of plasma homocysteine (p value \u3c 0.05), while all other polymorphisms did not show any significant difference in mean levels of homocysteine between AMI patients and healthy controls. Moreover, no association was observed between MTHFR C677T, A1298C; MS A2756C; CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population

A simple micro method for determination of plasma levels of alpha tocopherol (Vitamin E) in Pakistani normal adults.

A relatively simple spectrophotometeric method has been developed for the determination of alpha tocopherol in human plasma. Method is modification of a previous micromethod base on oxidation of alpha tocopherol by ferric chloride. The complex of ferrous ions (generated in this reaction) with bathophenanthroline is determined spectrophotometrically at 536 nm. The absorbance of this colored complex is directly proportional to concentration of alpha tocopherol. The method involves extraction of alpha tocopherol from human plasma using n-hexane which is relatively less toxic than xylene. The assay is sensitive enough to detect as little as 0.2 mug of vitamin. The recovery of alpha tocopherol from the plasma using n-hexane was in the range of 75% - 100%. The mean values of intra-assay and interassy coefficient of variation were found to be 5.3% and 13%, respectively. The assay was used to monitor alpha tocopherol levels in plasma samples of 81 normal healthy adults. Mean concentration of plasma alpha tocopherol in these normal healthy adults was found to be 9.45+/-2.64 microg/ ml. Sixteen percent of adults had low levels of alpha tocopherol. The method is rapid, convenient, reproduciable and relatively less hazardous compared to methods using xylene for the extraction of vitamin E. It can be routinely used to analyze as many as 20 plasma samples in about 2 hours time

Does vitamin E have a role in treatment and prevention of anemia?

Vitamin E is a highly effective fat-soluble vitamin with a variety of cellular membrane stabilizing-antioxidant and non-antioxidant functions. Vitamin E has been suggested to prevent the oxidation of polyunsaturated fatty acids in red blood cell (RBC) membrane, thus inhibiting the premature erythrocytelysis. Animal studies have shown that treatment with vitamin E results in increased number of colony forming units of erythroid precursors, enhanced erythropoiesis and improved blood hemoglobin levels in these animals. Several clinical trials have indicated that vitamin E might be used therapeutically as a potential erythropoietic agent for decreasing the premature erythrocyte hemolysis by reducing the fragility of erythrocytes. By this way, it improves the post-supplemental blood hemoglobin and hematocrit levels in some of the anemic human subjects, including low birth weight premature infants, Patients suffering from various types of inherited hemolytic anemia, chronic renal failure Patients on hemodialysis and apparently healthy mildly anemic subjects