Indian Pediatr 2015;52: 380-381
and Folic Acid: Significance in Human Health
From the Division of Community Studies, National
Institute of Nutrition, Indian Council of Medical Research, Hyderabad,
and folic acid are essential for formation of red blood cells, and are
also believed to prevent disorders of central nervous system, mood
disorders, and dementia . Nutritional anemia due to vitamin B12
and/or folate deficiency is generally associated with
hyperhomo-cysteinemia, which has been linked with pregnancy
complications like pre-eclampsia, recurrent pregnancy loss and
intra-uterine growth restriction . A common cause of vitamin B12
deficiency is poor intake or absorption mediated by three transport
proteins viz haptocorrin (HC), intrinsic factor (IF) and
transcobalamin II (TCII). The deficiency is more common among
vegetarians because they lack vitamin B12
in their diets . Some of gastrointestinal diseases, such as Celiac
disease or Crohn’s disease which interfere with food absorption, may
also lead to vitamin B12
deficiency . Several studies from many parts of India (Bengaluru,
Chennai, Delhi, Hyderabad, Pune, Varanasi) suggest that a large
proportion of individuals (20-40%) are deficient in vitamin B12
and folic acid, presumably due to adherence to a strict vegetarian diet.
Reports also suggest that polymor-phisms in genes involved in vitamin B12
absorption also contribute to the large pool of vitamin B12
deficiency. The National Health and Nutrition Examination Survey also
estimated that 3.2% of adults over age 50 have a seriously low vitamin B12
level, and up to 20% may have a borderline deficiency. Large amounts of
folic acid can mask the damaging effects of vitamin B12
deficiency by correcting the megaloblastic anemia caused by vitamin B12
deficiency has also been associated with dysfunctional immune response
leading to increased susceptibility to infections. The study published
in this issue of Indian Pediatrics  has observed the effect of
nutritional parameters, serum albumin, folate and vitamin B12
levels in children with acute lymphoblastic leukemia (ALL) on recovery
of bone marrow and peripheral blood counts as well as mortality during
induction phase. The authors observed that a significant decline in
folate levels on serial assays during chemotherapy, and folate-deficient
children had higher risk for delayed marrow recovery and counts on day
14. Hypo-albuminemia, and vitamin B12
and folate deficiencies were associated with toxic deaths during
induction phase of ALL. A consistent and significant decline in serial
folate levels during initial two months of chemotherapy revealed that
there could be an increased demand for folic acid and vitamin B12
in the presence of ALL, or it may be due to drug and nutrient
interaction, which needs to be further explored. In multivariate
analysis, folate deficiency continued to be a significant risk factor
for incomplete bone marrow recovery and delayed recovery of counts. As
the sample size is small, no convincing pathophysiology was established
to support these findings. Further, there are two areas where vitamin B12
nutrition needs physiological research in India – first, in terms of its
absorption, and second, in terms of functional indices of its
The road to curing most children with acute
lymphoblastic leukemia (ALL), the most common childhood cancer, may be
the greatest success story in the history of cancer. The modern therapy
for childhood ALL began in Boston when Dr. Sidney Farber, a pathologist
at the Children’s Hospital, developed an interest in childhood leukemia.
Farber wondered whether folic acid would also cure ALL because it too
featured immature blood cells and anemia. He tried it in some children,
but it failed. He then reasoned that folic acid may have stimulated the
growth of leukemia cells as well as normal cells and instead tried to
block that stimulation with an antagonist of folic acid, aminopterin.
Methotrexate (MTX) is an anti-cancer and antifolate drug that inhibits
cell division by reducing intracellular amounts of reduced
tetrahydrofolates. Experimental data have shown that increased folate
concentrations intracellularly inhibit MTX metabolism and toxicity. It
was concluded that folic acid supplements of 75-200 µg/day affect the
proliferative capacity of the bone marrow. Sadananda, et al. 
reported that folate levels were significantly high among ALL patients
as compared to normal children. Although individually vitamin B12
and homocysteine were not significantly different
between ALL and normals, the combined effect of all three parameters was
significantly different. Thus, in the given context of public health
significance; a comprehensive epidemiological and genetic study is
necessary to understand the burden of vitamin B12
deficiency across the diverse geographical regions
of the country. The authors also reported that the effect of
undernutrition was not seen on the prognosis with ALL chemotherapy,
which could be due to high prevalence of undernutrition (66%) among the
studied population. Generally, high micronutrient deficiencies are a
common phenomenon in all the children with high undernutrition .
Furthermore, the quality of the evidence is weak overall because most
studies to date were cross-sectional, and established temporal
relationship between vitamin B12 and folic acid, and ALL. Therefore,
early detection and treatment is important. The studies should aim to
assess the burden of vitamin B12
deficiency throughout the country vis-ŕ-vis
deficiency of the two other micronutrients, folate and iron.
Funding: None; Competing Interest: None
1. Hanna S, Lachover L, Rajarethinam RP. Vitamin B‚
deficiency and depression in the elderly: review and case report. Prim
Care Companion J Clin Psychiatry. 2009;11:269-70.
2. Nelen WL, Blom HJ, Steegers EA, den Heijer M,
Thomas CM, Eskes TK. Homocysteine and folate levels as risk factors for
recurrent early pregnancy loss. Obstet Gynecol. 2000;95:519-24.
3. Pawlak R, Lester SE, Babatunde T. The prevalence
of cobalamin deficiency among vegetarians assessed by serum vitamin B12:
A review of literature. Eur J Clin Nutr. 2014; 68:541-8.
4. Battat R, Kopylov U, Szilagyi A, Saxena A,
Rosenblatt DS, Warner M, et al. Vitamin B12 deficiency in
inflammatory bowel disease: prevalence, risk factors, evaluation, and
management. Inflamm Bowel Dis. 2014;20:1120-8.
5. Goyal V. Vitamin B12. IOSR Journal of Pharmacy.
6. Tandon S, Moulik NR, Kumar A, Mahdi AA, Kumar A.
Effect of pre-treatment nutritional status, folate and vitamin B12
levels on induction chemotherapy in children with acute lymphoblastic
leukemia. Indian Pediatr. 2015;52:385-9.
7. Sadananda Adiga MN, Chandy S, Ramaswamy G, Appaji
L, Krishnamoorthy L. Homocysteine, vitamin B12 and folate status in
pediatric acute lymphoblastic leukemia. Indian J Pediatr. 2008;75:235-8.
8. Laxmaiah A, Arlappa N, Raghu P, Balakrishna N,
Mallikharjuna Rao K, Galreddy C, et al. Prevalence and
determinants of micronutrient deficiencies among rural children in 8
states of India. Ann Nutr Metab. 2013; 62:229-39.