A small study carried out in Sangli, Maharashtra on 43 women participants to evaluate the effectiveness of tea fortification with folate and vitamin B12 to address anaemia and prevent neural-tube defects in children is riddled with problems.
The results were published in the BMJ Nutrition, Prevention & Health.
The participants were divided into three groups. The first group had 19 women who were given tea fortified with 1 mg folate and 0.1 mg vitamin B12. The second group (19 women) was given tea fortified with 1 mg folate and 0.5 mg vitamin B12. The third was the control group but with a “limited number” of participants (five).
“Usually, the number of participants is decided based on the statistical power of the comparison, which in turn is dependent on the expected difference and its variability. None of these are defined. Thus, a “limited number” of controls is not the way to go,” Dr. Anura Kurpad, Professor of Physiology in St John’s Medical College, Bengaluru, says in an email to The Hindu.
Since the number of participants in the control arm is less, the authors used pre- and post-intervention values to measure the efficacy of folate and vitamin B12 intervention. However, this approach has a fundamental problem.
“Pre- and post-interventions are subject to any number of confounders that could have caused the observed changes. Having a control group eliminates the known and unknown confounders, and participants should be randomised to any of the groups. None of these conditions were fulfilled,” Dr. Kurpad says.
Whether the participants were given folate or folic acid is not clear as references to both are made in the paper. According to him, for folate, the recommended ceiling on intake (also called the tolerable upper limit of intake) is 1 mg/day. For folic acid, it will be about half of that (0.5 mg/day). If 1 mg/day of folic acid was given, it had certainly exceeded the upper limit.
The dose of food folate for women is about 0.2 mg/day, while periconception requirement is set at 0.48 mg/day. These values are for dietary folate. Since folic acid is absorbed so much better, only about 50% of food folate dose is required.
A bigger problem is about measuring haemoglobin levels after intervention. While the study claims that haemoglobin counts increased post-intervention, the fact is that haemoglobin level was not measured for all participants. “Due to an inadvertent communication error, post-intervention haemoglobin levels were not uniformly obtained in all three groups,” the paper says. So, it is not certain that elevated levels of folate and vitamin B12 post-intervention have necessarily led to increased haemoglobin levels in all participants.
Another shortcoming of the study has been the focus on folate and vitamin B12 fortification of tea without taking iron into consideration. Anaemia can be caused due to deficiency of iron, vitamin B12 and/or folic acid. So fortification using only folate and vitamin B12 may not be sufficient to address the problem of anaemia in women.
“Focusing on one or two nutrients in the complex mixture of nutrients required for making haemoglobin in the body is a mistake. It causes imbalances in nutrients in the body, and both folic acid and B12 in excess are not without potential dangers,” cautions Dr. Kurpad.
There are no national level surveys of Indian women that have measured haemoglobin along with markers of iron status (like ferritin). A few small studies in India suggest that 50% of anaemia is due to iron deficiency. The Comprehensive National Nutrition Survey (CNNS) of Indian children aged 1-19 years measured haemoglobin and other markers such as ferritin for iron, and serum B12 and folate levels.
“In adolescent girls (10-19 years), folate and B12 deficiency anaemia was present in 22%. Iron deficiency anaemia was seen in 27% of girls. Anaemia due to unknown origin and inflammation accounted for 31%,” he says.
To prevent neural-tube defects, the requirement during pregnancy is 0.48 mg per day of dietary folate (or about 50% of that as folic acid). However, a specific ‘periconceptional folate’ requirement has not been defined in India.
“But, paediatricians suggest 0.4 mg/day of folic acid from one month prior to pregnancy. This amount is not possible from the current fortification levels recommended in India and should be taken as a tablet,” says Dr. Kurpad.