PMID- 25841618
OWN - NLM
STAT- MEDLINE
DCOM- 20160301
LR  - 20161125
IS  - 1879-0739 (Electronic)
IS  - 0271-5317 (Linking)
VI  - 35
IP  - 6
DP  - 2015 Jun
TI  - Cyclic supplementation of 5-MTHF is effective for the correction of 
      hyperhomocysteinemia.
PG  - 489-95
LID - S0271-5317(15)00042-1 [pii]
LID - 10.1016/j.nutres.2015.02.006 [doi]
AB  - Folic acid supplementation is the mainstay treatment of hyperhomocysteinemia 
      (HHcy). However, no recommendations are currently available in regard to the 
      optimal replacement therapy. Therefore, this prospective study hypothesized that 
      a cyclic schedule (1 month of therapy followed by 2 months of withdrawal) of 
      5-methyltetrahydrofolate (5-MTHF) would reduce plasma levels of fasting total 
      homocysteine (tHcy) in patients with mild/moderate HHcy. Patients with a new 
      diagnosis of mild/moderate HHcy were evaluated for the methylenetetrahydrofolate 
      reductase genotype and the presence of major features of metabolic syndrome. All 
      enrolled subjects received a cyclic 5-MTHF oral supplementation and were 
      reevaluated after each treatment cycle for a total of 2 years. In the 246 
      enrolled subjects, a significant reduction of tHcy levels occurred after the 
      first cycle of treatment (from 31.6 +/- 13.6 to 14.4 +/- 5.77 mumol/L, P < .001) and 
      during the whole 2-year follow-up (from 31.6 +/- 13.6 to 12.18 +/- 3.03 mumol/L, P < 
      .001). The values of tHcy returned to reference range in 117 subjects (51.3%) 
      after the first cycle and in 198 (86.8%) during the follow-up. The risk of 
      failure in tHcy level normalization was increased in patients with metabolic 
      syndrome (hazard ratio [HR], 3.49; 95% confidence interval [CI], 1.46-8.36), 
      higher baseline tHcy levels (HR, 1.045; 95% CI, 1.018-1.073), or 
      methylenetetrahydrofolate reductase homozygous mutation (HR, 6.59; 95% CI, 
      2.64-16.4). This study clearly shows that a cyclic schedule (1 month of therapy 
      followed by 2 months of withdrawal) of 5-MTHF supplementation is able to 
      significantly reduce tHcy levels in patients with mild/moderate HHcy.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Ambrosino, Pasquale
AU  - Ambrosino P
AD  - Department of Clinical Medicine and Surgery, Federico II University, Naples, 
      Italy.
FAU - Lupoli, Roberta
AU  - Lupoli R
AD  - Department of Clinical Medicine and Surgery, Federico II University, Naples, 
      Italy.
FAU - Di Minno, Alessandro
AU  - Di Minno A
AD  - Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro 
      Cardiologico Monzino, IRCCS, Milan, Italy.
FAU - Nardo, Assunta
AU  - Nardo A
AD  - Department of Clinical Medicine and Surgery, Federico II University, Naples, 
      Italy.
FAU - Marrone, Emiliana
AU  - Marrone E
AD  - Department of Clinical Medicine and Surgery, Federico II University, Naples, 
      Italy.
FAU - Lupoli, Valentina
AU  - Lupoli V
AD  - Department of Pharmacy, Federico II University, Naples, Italy.
FAU - Scaravilli, Alessandra
AU  - Scaravilli A
AD  - Department of Clinical Medicine and Surgery, Federico II University, Naples, 
      Italy.
FAU - Mitidieri, Emma
AU  - Mitidieri E
AD  - Department of Pharmacy, Federico II University, Naples, Italy.
FAU - Tufano, Antonella
AU  - Tufano A
AD  - Department of Clinical Medicine and Surgery, Federico II University, Naples, 
      Italy.
FAU - Di Minno, Matteo Nicola Dario
AU  - Di Minno MN
AD  - Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro 
      Cardiologico Monzino, IRCCS, Milan, Italy. Electronic address: 
      dario.diminno@hotmail.it.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20150226
PL  - United States
TA  - Nutr Res
JT  - Nutrition research (New York, N.Y.)
JID - 8303331
RN  - 0 (Tetrahydrofolates)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
RN  - TYK22LML8F (5-methyltetrahydrofolate)
SB  - IM
MH  - Adult
MH  - *Dietary Supplements
MH  - Female
MH  - Genotype
MH  - Homocysteine/*blood/genetics
MH  - Humans
MH  - Hyperhomocysteinemia/blood/*drug therapy/genetics
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/*genetics
MH  - Middle Aged
MH  - Prospective Studies
MH  - Tetrahydrofolates/*administration & dosage/therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - 5-Methyl-tetra-hydro-folate
OT  - Cyclic folate supplementation
OT  - Folate
OT  - Homocysteine
OT  - Hyperhomocysteinemia
OT  - Patient
EDAT- 2015/04/07 06:00
MHDA- 2016/03/02 06:00
CRDT- 2015/04/06 06:00
PHST- 2014/09/27 00:00 [received]
PHST- 2015/02/16 00:00 [revised]
PHST- 2015/02/23 00:00 [accepted]
PHST- 2015/04/06 06:00 [entrez]
PHST- 2015/04/07 06:00 [pubmed]
PHST- 2016/03/02 06:00 [medline]
AID - S0271-5317(15)00042-1 [pii]
AID - 10.1016/j.nutres.2015.02.006 [doi]
PST - ppublish
SO  - Nutr Res. 2015 Jun;35(6):489-95. doi: 10.1016/j.nutres.2015.02.006. Epub 2015 Feb 
      26.