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Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia
Department of Laboratory, Foundation of Research and Care, "John Paul II", Catholic University of Sacred Heart, Campobasso 86100, Italy
ICBD, Alessandra Lisi International Centre on Birth Defects and Prematurity, Rome 00100, Italy
Department of Laboratory Medicine, Policlinico A. Gemelli, Catholic University of Sacred Heart, Rome 00168, Italy
Research Laboratories, Foundation of Research and Care, "John Paul II", Catholic University of Sacred Heart, Campobasso 86100, Italy
National Institute of Research for Foods and Nutrition (Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione), Rome 00178, Italy
Department of Pediatrics, Federico II University, Neaples 81100, Italy
Department of Pediatrics, Catholic University of Sacred Heart, Rome 00168, Italy
* Author to whom correspondence should be addressed.
Received: 17 January 2013; in revised form: 22 March 2013 / Accepted: 10 April 2013 / Published: 8 May 2013
Abstract: To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with “moderate” hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Subjects/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 μg from a natural folate-rich diet, 200 μg [6S]5-methyltetrahydrofolate (5-MTHF), 200 μg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy) levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002), 19.4% (p < 0.001) and 21.9% (p < 0.001), as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid). After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations.
Keywords: folic acid; 5-MTHF; homocysteine; folate-rich diet; MTHFR genotype; clinical trial
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Zappacosta, B.; Mastroiacovo, P.; Persichilli, S.; Pounis, G.; Ruggeri, S.; Minucci, A.; Carnovale, E.; Andria, G.; Ricci, R.; Scala, I.; Genovese, O.; Turrini, A.; Mistura, L.; Giardina, B.; Iacoviello, L. Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia. Nutrients 2013, 5, 1531-1543.
Zappacosta B, Mastroiacovo P, Persichilli S, Pounis G, Ruggeri S, Minucci A, Carnovale E, Andria G, Ricci R, Scala I, Genovese O, Turrini A, Mistura L, Giardina B, Iacoviello L. Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia. Nutrients. 2013; 5(5):1531-1543.
Zappacosta, Bruno; Mastroiacovo, Pierpaolo; Persichilli, Silvia; Pounis, George; Ruggeri, Stefania; Minucci, Angelo; Carnovale, Emilia; Andria, Generoso; Ricci, Roberta; Scala, Iris; Genovese, Orazio; Turrini, Aida; Mistura, Lorenza; Giardina, Bruno; Iacoviello, Licia. 2013. "Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia." Nutrients 5, no. 5: 1531-1543.