Download Biotin and Folic Acid deficiency

Finecure Update
Foetop
A Passi Publication
Folic acid and biotin:
Growing evidence that their levels are far more important
than we knew them to be
Biotinidase deficiency
Biotinidase is the enzyme responsible for the recycling of the
vitamin biotin. Biotinidase acts as a hydrolase by cleaving biocytin
and biotinyl-peptides, thereby liberating biotin for reutilization.
Biotinidase is also important for making biotin bioavailable from
bound dietary sources. The interest in this enzyme has been
increased by the discovery of biotinidase deficiency, an inherited
biotin-responsive disorder that can result in neurological and
cutaneous abnormalities.
Recent reports have stressed the need to screen children with
early onset of seizures, encephalopathy, neurodevelopmental delay,
skin rash and alopecia. Enzyme estimation remains the conclusive
test. The clinician should be alert to simple clinical pointers which
aid in early diagnosis of these disorders.1
•
Biotin, a water-soluble vitamin of the B complex, functions as a
cofactor of carboxylases that catalyze an indispensable cellular
metabolism. Although significant decreases in serum biotin levels
have been reported in patients with chronic inflammatory diseases.
In a study, experts investigated the effects of biotin deficiency on
TNF-alpha production. The results indicated that biotin deficiency
may up-regulate TNF-alpha production or that biotin excess downregulates TNF-alpha production, suggesting that biotin status may
influence inflammatory diseases.2
•A
•
Alterations in the intestinal flora caused by the prolonged
administration of antibiotics are presumed to be the basis for
biotin deficiency.
Biotin deficiency up-regulates
TNF-alpha production
Causes of biotin deficiency
•
supplemental biotin, in addition to the usual minimum
daily requirements, has been suggested for patients who are
treated with anticonvulsants that have been linked to biotin
deficiency.
diet that contains raw egg whites quickly and almost
invariably leads to biotin deficiency.
Several cases of biotin deficiency in patients receiving prolonged
total parenteral nutrition (TPN) therapy without added biotin
have been reported. Therefore, all patients receiving TPN must
also receive biotin at the recommended daily dose, especially if
TPN therapy is expected to last more than 1 week. All hospital
pharmacies currently include biotin in TPN preparations.
Biotin in type 2 diabetic patients and in
nondiabetics with hypertriglyceridemia
Biotin is a water-soluble vitamin that acts as a prosthetic group of
carboxylases. Several studies have reported a relationship between
biotin and blood lipids. In the present work3 experts investigated
the effect of biotin administration on the concentration of plasma
lipids, as well as glucose and insulin in type 2 diabetic and
Prolonged use of certain drugs, especially phenytoin, primidone,
and carbamazepine, may lead to biotin deficiency. Therefore,
1
Finecure Update
Spinal cord demyelination with
biotinidase deficiency
nondiabetic subjects. They found that the vitamin significantly
reduced (P=0.005) plasma triacylglycerol and VLDL
concentrations.
Biotin produced the following changes (mean of absolute
differences between 0 and 28 day treatment ± S.E.M.): a)
triacylglycerol -0.55 ± 0.2 in the diabetic group and -0.92 ± 0.36 in
the nondiabetic group; b) VLDL: -0.11 ± 0.04 in the diabetic group
and -0.18 ± 0.07 in the nondiabetic group. It was concluded that
pharmacological doses of biotin decrease hypertriglyceridemia.
Biotinidase deficiency is a treatable cause of severe neurological
disorders and skin problems. Spinal cord impairment is a rare
complication of this disease and is commonly unrecognized.
Findings indicate that biotinidase deficiency should be considered in
the differential diagnosis of unexplained spinal cord demyelination
because prompt diagnosis and treatment with biotin may enable
an excellent recovery.5
Low serum biotinidase activity in
children with valproic acid
Biotin Supplement During Pregnancy
A deficiency of biotin may occur in as many as 50% of pregnant
women, and this deficiency may increase the risk of birth defects,
according to a report in the American Journal of Clinical
Nutrition (2002;75:295–9). In this study, laboratory evidence of
biotin deficiency was found both in the early (first trimester) and
late (third trimester) stages of pregnancy, and was corrected by
supplementation.
Prior to this study, it had been generally believed that biotin
deficiency is rare, because biotin is found in a wide variety of foods
and is also manufactured by intestinal bacteria. This new study
indicates that a more subtle form of biotin deficiency occurs during
pregnancy, possibly as a result of the increased demand for nutrients
placed on the mother by the growing fetus.
Researchers have recommended that pregnant women use a
prenatal multiple vitamin-and-mineral formula that contains biotin.
Taking a biotin-containing prenatal formula seems a reasonable step
for pregnant women, since the vitamin is considered safe and has
not been associated with adverse side effects. At least 25 countries
have included biotinidase deficiency in their screening programs
for neonatal disease.
Biotin supplements have also been used for several other health
conditions. Preliminary studies have suggested that biotin in large
amounts (such as 5 to 16 mg per day) can help control blood sugar
levels or improve nerve damage in diabetics.
Valproic acid (VPA) is an effective antiepileptic drug (AED), which
is associated with dose-related adverse reactions such as skin rash,
hair loss (alopecia), etc. Profound as well as partial biotinidase
deficiency causes dermatologic manifestations similar these.
Therefore, it was of interest to evaluate serum biotinidase activity
in patients receiving VPA monotherapy. It is suggested that VPA
impairs the liver mitochondrial function, resulting in a low biotinidase
activity and or biotin deficiency. Biotin supplementation could restore
some of the side effects of the drug.6
role of Folic acid in lowering cvd
The B vitamins are water-soluble vitamins that are required as
coenzymes for reactions essential for cellular function. Plasma
homocysteine (tHcy) is very responsive to intervention with
the B-vitamins required for its metabolism, in particular folic
acid. Supplementation with oral folate and vitamins B6 and B12
(mainly folate) reduce plasma homocysteine levels to a significant
degree. Thus, although primarily aimed at reducing neural-tube
defects, folic acid fortification may have an important role in the
primary prevention of cardiovascular diseases (CVD) via tHcy
lowering. During the last years, many epidemiologic studies
have identified homocysteine as an independent risk factor for
cardiovascular diseases like coronary events, stroke, and venous
thromboembolism.
Recent trials showed that vitamin supplementation leads to
slower progression or even regression of atherosclerotic lesions in the
carotid arteries, as confirmed by ultrasonographic measurement of
carotid intima media thickness. In fact, a recent meta-analysis of
clinical trials has confirmed that folic acid supplementation reduces
the risk of stroke, particularly in individuals without a history of
stroke.
Evidence supporting a causal relationship between elevated
tHcy and heart disease also comes from genetic studies. The most
important genetic determinant of tHcy in the general population
is the common C677T variant in methylenetetrahydrofolate
reductase (MTHFR) that results in higher tHcy. Individuals with the
homozygous mutant (TT) genotype have a significantly higher (1421%) risk of heart disease.7
Marginal biotin deficiency is teratogenic
Studies of biotin status during pregnancy provide evidence that a
marginal degree of biotin develops in a substantial proportion of
women during normal pregnancy. Several lines of evidence suggest
that, although the degree of biotin deficiency is not severe enough
to produce the classic cutaneous and behavioral manifestations
of biotin deficiency, the deficiency is severe enough to produce
metabolic derangements in women and that characteristic fetal
malformations occur at a high rate.
Moreover, analysis of data from a published multivitamin
supplementation study provide significant albeit indirect evidence that
the marginal degree of biotin deficiency that occurs spontaneously
in normal human gestation is teratogenic.
Reduced activity of the biotin-dependent enzymes acetyl-CoA
carboxylase and propionyl-CoA carboxylase can cause alterations
of lipid metabolism and might theoretically lead to alterations of
polyunsaturated fatty acid and prostaglandin metabolism that derange
normal skeletal development.4
folic acid deficiency causes
neurological and psychiatric diseases
Hyperhomocysteinemia (HHcy) is also related to central nervous
system diseases. Epidemiological studies show a positive, dose-
DrugCompositionPackingAdministration
Foetop 10
Biotin U.S.P. 5 mg Folic Acid 5 mg
10 Tablets
1 OD
2
Finecure Update
dependent relationship between plasma total homocysteine (tHcy)
concentration and neurodegenerative disease risk. tHcy is a marker
of B-vitamin folate, B12, B6 status. Hypomethylation, caused by
low B-vitamin status and HHcy, is linked to key pathomechanisms
of dementia; B-vitamin supplementation could potentially reduce
neurological damage.
In retrospective studies, the association between tHcy and
cognition is impressive; there is also evidence that tHcy-lowering
treatment could be effective in primary and secondary stroke
prevention. Increased tHcy and low serum folate occur in patients
with Parkinson’s disease, especially those receiving L-dopa. There
is also an association between HHcy and multiple sclerosis, and
between B-vitamin status and depression.
Studies also confirm a causal role for tHcy in epilepsy, and
certain anti-epileptics enhance HHcy. B-vitamin status should
be optimized by ensuring sufficient intake in patients with
neuropsychiatric diseases. HHcy occurs commonly in the elderly and
can contribute to age-related neurodegeneration. Treatment with folic
acid, B12 and B6 lowers tHcy. For secondary and primary prevention
from several neuropsychiatric disorders, it seems prudent to actively
Dr. Naima K. Chaudhary, MS
Senior Specialist, Department of G&O,
St. Stephen's' Hospital, Delhi
Doctor opines...
Folic acid and biotin are two very important
supplements responsible for many disease
conditions. This is even more true in
developing countries where these deficiencies exist on a large
scale in certain conditions such as in the pregnant women and
elderly.
identify deficient subjects and ensure sufficient vitamin intake.8
The aim of this study was to determine whether hyperhomocysteinemia caused by levodopa used in idiopathic Parkinson’s
disease (IPD) is associated with cognitive or physical impairments.
The conclusion that was arrived at was that in those patients with
IPD who are detected to have hyperhomocysteinemia, the assessment
of the cognitive performance, folic acid and vitamin B12 levels and
the supplementation of folic acid and vitamin B12 to the treatment
regimen might be appropriate.9
Highlights
•
•
•
•
•
•
•
•
inflammatory bowel disease: the
role of folate deprivation
A deficiency of biotin may occur in as many as 50% of
pregnant women, and this deficiency may increase the risk of
birth defects, according to a report in the American Journal
of Clinical Nutrition
Homocysteine has a crucial role in cellular stress, epigenetic
events, inflammatory processes, and host-microbial interactions.
Moderate hyperhomocysteinemia is a complex trait associated with
inflammatory bowel disease (IBD). Furthermore, the relevance of
screening and treating folate and vitamin B12 deficiencies in IBD
subjects can now be relevant. In IBD, normalizing vitamin levels
should be an integral part of the management of these patients,
especially those with active disease, history of intestinal resection,
and/or treated with methotrexate.10
The relevance of screening and treating folate deficiencies in
IBD subjects can be relevant. In IBD, normalizing vitamin
levels should be an integral part of the management of
these patients, especially those with active disease, history
of intestinal resection, and/or treated with methotrexate
Several lines of evidence suggest that biotin deficiency
is severe enough to produce metabolic derangements in
women and that characteristic fetal malformations occur at
a high rate. Marginal degree of biotin deficiency that occurs
spontaneously in normal human gestation is teratogenic
References
1. Gulati S, Passi GR, Kumar A, Kabra M, Kalra V, Verma IC. Biotinidase deficiency--a
treatable entity. Indian J Pediatr. 2000 Jun; 67(6): 464-6.
2. Kuroishi T, Endo Y, Muramoto K, Sugawara S. Biotin deficiency up-regulates TNFalpha production in murine macrophages. J Leukoc Biol. 2008 Apr; 83(4): 912-20.
3. Revilla-Monsalve C, Zendejas-Ruiz I, Islas-Andrade S et al. Biotin supplementation
reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic
subjects with hypertriglyceridemia. Biomed Pharmacother. 2006 May; 60(4): 182-5.
4. Zempleni J, Mock DM. Marginal biotin deficiency is teratogenic. Proc Soc Exp Biol
Med. 2000 Jan; 223(1): 14-21.
5. Yang Y, Li C, Qi Z, Xiao J, Zhang Y, Yamaguchi S, Hasegawa Y, Tagami Y, Jiang
Y, Xiong H, Zhang Y, Qin J, Wu XR. Spinal cord demyelination associated with
biotinidase deficiency in 3 Chinese patients. J Child Neurol. 2007 Feb; 22(2): 156-60.
6. Schulpis KH, Karikas GA, Tjamouranis J, Regoutas S, Tsakiris S. Low serum
biotinidase activity in children with valproic acid monotherapy. Epilepsia. 2001 Oct;
42(10): 1359-62.
7. McNulty H, Pentieva K, Hoey L, Ward M. Homocysteine, B-vitamins and CVD. Proc
Nutr Soc. 2008 May; 67(2): 232-7.
8. Obeid R, McCaddon A, Herrmann W. The role of hyperhomocysteinemia and B-vitamin
deficiency in neurological and psychiatric diseases. Clin Chem Lab Med. 2007; 45(12):
1590-606.
9. Ozer F, Meral H, Hanoglu L, Aydemir T, Yilsen M, Cetin S, Ozturk O, Seval H, Koldas
M. Plasma homocysteine levels in patients treated with levodopa: motor and cognitive
associations. Neurol Res. 2006 Dec; 28(8): 853-8.
10. Peyrin-Biroulet L, Rodriguez-Guéant RM, Chamaillard M, Desreumaux P, Xia B,
Bronowicki JP, Bigard MA, Guéant JL. Vascular and cellular stress in inflammatory
bowel disease: revisiting the role of homocysteine. Am J Gastroenterol. 2007 May;
102(5): 1108-15.
Taking a biotin-containing prenatal formula seems a reasonable
step for pregnant women, since the vitamin is considered
safe and has not been associated with adverse side effects
In normal circumstances, homocysteine is converted to
cysteine and partly remethylated to methionine with the help of
Vit. B12 and folate. Homocysteine, formed from methionine
has profound importance in health and diseases
Although primarily aimed at reducing neural-tube defects,
folic acid fortification may have an important role in the
primary prevention of cardiovascular diseases via plasma
homocysteine lowering
In hyperhomocysteinemias, clinical manifestations are
mental retardation and seizures (type I only), ectopia lentis,
secondary glaucoma, optic atrophy, retinal detachment, skeletal
abnormalities, osteoporosis, vascular changes, neurological
dysfunction and psychiatric symptoms. Thrombotic and
cardiovascular diseases may also be encountered
A recent meta-analysis of clinical trials has confirmed that folic
acid supplementation reduces the risk of stroke, particularly
in individuals without a history of stroke.
3