Das “Homocystein Expert Panel” bietet neben grundlegenden Informationen zum Thema Homocystein auch eine ständig aktualisierte Liste der wichtigsten Studien: Homocystein Expert Panel – Studien
weitere Studien:
B-Vitamine nach Schlaganfall verringern Depression Risiko
Bericht der VITATOPS-DEP-Studie von Almeida OP, et al.
273 Patienten, die kürzlich einen Schlaganfall erlitten (innerhalb von 7 Monaten nach dem Schlaganfall) und überlebt haben, wurden durchschnittlich 7,1 Jahre lang (mindestens 1 Jahr, höchstens 10,5 Jahre) entweder mit B-Vitaminen oder einem Placebo supplementiert. Die orale Vitamindosis bestand aus täglich 2 mg Folsäure, 0,5 mg Vitamin B12 und 25 mg Vitamin B6. 18,4% der Probanden der Vitamingruppe und 23,3% der Placebogruppe entwickelten eine Depression während des Beobachtungszeitraums. Die Wahrscheinlichkeit, dass Patienten, die mit Vitaminen behandelt wurden, eine Depression entwickelten, war um 50% geringer als in der Placebogruppe. Der Unterschied des Effekts zwischen Vitaminen und Placebo scheint nach 5-6 Jahren aufzutreten.
Empfehlungen:
- Depressionen betreffen 1 von 3 überlebenden Schlaganfallpatienten und verursachen so eine zusätzliche Quelle an Erkrankungen, Kosten und funktionellen Beeinträchtigungen.
- Schlaganfall und Depression teilen sich viele Risikofaktoren, wie z.B. erhöhte Plasmakonzentrationen von Homocystein. Homocystein kann durch eine einfache, sichere und kosteneffektive Einnahme von B-Vitaminen (Folsäure, B12 und B6) gesenkt werden.
- Die Studie von Almeida OP, et al. deutet darauf hin, dass eine Langzeit-Supplementation (> 7 Jahre) mit B-Vitaminen nach einem Schlaganfall das Risiko eine Depression zu bekommen um 50% verringert.
Ergänzung zur Studie von Almeida OP, et al.:
Die Studie war randomisiert und placebokontrolliert. Das bedeutet, dass die Patienten zufällig ausgewählt entweder Vitamine oder Placebo erhalten haben.
Die Studie war doppelblind bis zum Ende der Studie. Das bedeutet, dass weder die Patienten noch die behandelnde Ärzte wussten, in welchem Behandlungsarm (Vitamin- oder Placebogruppe) die Patienten waren.
Langzeit Metformin-Therapie verursacht niedrigen Vitamin B12-Spiegel
de Jager, et al., BMJ;2010;340:c2181
PMID: 20488910 [PubMed – indexed for MEDLINE]PMCID: PMC2874129
Metformin ist das am häufigsten verschriebene Medikament für Patienten mit Typ II Diabetes mellitus. Die häufigsten Todesursachen bei Patienten mit Typ II Diabetes sind Gefäßerkrankungen (Herzinfarkt, Schlaganfall) und Niereninsuffizienz. Hyperhomocysteinämie ist ein zusätzlicher und unabhängiger Risikofaktor für vaskuläre Begleiterkrankungen bei Patienten mit Diabetes. Mehrere Studien berichteten, dass Metformin Malabsorption von Vitamin B12 und Folat und daher Hyperhomocysteinämie verursacht (1-3).
Eine neue Studie von de Jager et al. bezog 390 Patienten aus Holland mit Diabetes Typ II ein (4). Die Patienten wurden mit Placebo oder mit Metformin (850 mg) / 3-mal pro Tag für 4,3 Jahre behandelt. Die Studie wurde nach einer Vorbehandlungsphase begonnen, in der Patienten für 12 Wochen nur Insulin gegeben wurde. Danach wurden die Patienten in zwei Gruppen unterteilt und erhielten 16 Wochen entweder Metformin oder Placebo. Anschließend konnten die Patienten weiterhin Metformin für 48 Monate in Anspruch nehmen. Die Placebo-Gruppe erhielt Insulin und war für die Behandlung von 16 Wochen bis zum Ende der Studie nicht verblindet.
Die Studie zeigte, dass Patienten, die mit Metformin behandelt waren, niedrigere Vitamin B12-Konzentrationen als die Placebo-Gruppe entwickelten (ca. 280 vs 365 pmol / l) und dass dieser Effekt über die Zeit anstieg.
Blut Folat waren auch niedriger in der Metformin-Gruppe als in der Placebo-Gruppe. Nach 4 Jahren hatten Patienten mit Vitamin-B12-Mangel Homocystein-Konzentrationen, die 59% höher als bei Patienten ohne B12-Mangel (14,9 vs 23,7 µmol / l) waren.
Kommentare und Empfehlungen
Die Studie von de Jager et al. zeigt, dass viele Patienten mit Diabetes einen klinisch relevanten Vitamin-B12-Mangel entwickelt haben. Vitamin B12-Mangel und Hyperhomocysteinämie sind kostengünstig und leicht zu behandeln. Die Supplementation mit B-Vitaminen im Bereich, der üblicherweise für die langfristige Prävention verwendet wird, ist sicher und ohne bekannte Nebenwirkungen (5). Die Studie legt nahe, dass bei Patienten mit Diabetes, die Metformin einnehmen, regelmäßig der Vitamin-Status getestet werden sollte und dass es ratsam ist B-Vitamine einzunehmen, bevor sich der Mangel entwickelt kann.
- Palomba S, Falbo A, Giallauria F, et al., Effects of metformin with or without supplementation with folate on homocysteine levels and vascular endothelium of women with polycystic ovary syndrome. Diabetes Care 2010;33:246-51.
- Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227-31.
- Ting RZ-W, Szeto CC, Chan MH-M, Ma KK, Chow KM. Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch Intern Med 2006;166:1975-9.
- de Jager J, Kooy A, Lehert P, et al., Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010 May 20;340:c2181.
- Hermann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int 2008;105:680-5.
Quelle: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874129/?tool=pubmed
Homocysteinsenkung durch B-Vitamine verlangsamt die Rate der beschleunigten Atrophie des Gehirns bei leichter kognitiver Beeinträchtigung: Eine randomisierte, kontrollierte Studie
Smith AD, et al., PLoS One. 2010 Sep 8;5(9):e12244.
Eine randomisierte, doppelblinde Studie wurde im UK durchgeführt. Es nahmen 168 ältere Menschen (>70 Jahre) mit leichter kognitiver Beeinträchtigung an der Studie teil. Die im Rahmen der Studie durchgeführte Vitaminbehandlung bestand aus einer täglichen Dosis von 0,8 mg Folsäure 0,5 mg Vitamin B12 und 20 mg Vitamin B6 über 24 Monate. Vor und nach der Behandlung wurden MRI Scans des Gehirns durchgeführt um die Rate der Gehirnatrophie zu untersuchen. Die Atrophie erhöhte sich in der Vitamingruppe jährlich um 0,76 % und in der Placebogruppe um 1,08 %. Dies entspricht einem um 30 % geringeren Voranschreiten der Atrophie bei Vitamineinnahme. Der Erfolg der Behandlung war abhängig vom Homocysteinspiegel vor Beginn der Supplementierung. Die Studie zeigte deutlich, dass die beschleunigte Hirnatrophie bei leichter kognitiver Beeinträchtigung durch eine einfache und kostengünstige Supplementation mit B-Vitaminen verlangsamt werden kann. Es konnte gezeigt werden, dass Probanden mit einem Homocysteinspiegel über 13 µmol/L mit höherer Wahrscheinlichkeit von der der Supplementation profitierten vergleich mit den jenigen die Homocystein > 10 hatten. Die Studie war nicht dafür ausgelegt Veränderungen der Kognitiven Funktionen zu untersuchen.
Allerdings deuten die Ergebnisse deutlich darauf hin, dass eine längere Vitamingabe das Vortschreiten der kognitiven Beeinträchtigung verringern sollte, da dieser direkt mit der Hirnatrophie korreliert.
Ungefähr 14-18% der älteren Menschen > 70 Jahre sind von leichter kognitiver Beeinträchtigung betroffen und bei der hälfte dieser Menschen wird sich die Erkrankung zur Demenz oder Morbus Alzheimer entwickeln.
Quelle: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935890/?tool=pubmed
Vitamin treatments that lower homocysteine concentration: can they decrease cerebrovascular disease in primary prevention?
Abstract
INTRODUCTION: High plasma homocysteine (Hcy) concentration or hyperhomocysteinemia is associated with an increased vascular risk of disease in case-control studies and, to a lesser extent, in prospective studies.
DEVELOPMENT: Several large randomized, double-blind, placebo-controlled trials have been already conducted using specific vitamin therapies with the aim of reducing secondary cardiovascular (HOPE, NORVIT, WAFACS and WENBIT studies) and cerebrovascular (VISP study) disease risk. The results from these major secondary prevention trials and one meta-analysis, that included other smaller studies up to 12 of them, showed that treatment decreased plasma Hcy concentration but failed to reduce cardiovascular risk. It is nevertheless noteworthy that a recent meta-analysis addressing the effects of these vitamin treatments on cerebrovascular risk found a positive effect on primary stroke prevention. These data would be consistent with the fact that increased Hcy is known to be associated more strongly with stroke risk than with cardiovascular risk. Moreover, folic acid supplementation in grain food has recently been shown to be associated with a decreased stroke incidence in USA and Canada.
CONCLUSIONS: Obviously, these data on primary stroke prevention will require extensive confirmation. However, there now appear to be more reasons to expect a positive outcome of Hcy intervention studies.
Link: http://www.ncbi.nlm.nih.gov/pubmed/20198596
Homocysteine levels and amyotrophic lateral sclerosis: A possible link.
Abstract
Homocysteine (Hcy) exerts multiple neurotoxic mechanisms that have also been shown to be relevant in the pathogenesis of amyotrophic lateral sclerosis (ALS). We reviewed the published evidence to assess possible correlations between Hcy and ALS. A Medline literature search was performed to identify all studies on Hcy and ALS or motor neurons published from 1 January 1966 through 28 February 2009. Twelve studies (one in vitro, eight in vivo, and three studies on human subjects) were reviewed. The in vitro and in vivo animal studies showed that Hcy can damage motor neurons by inducing oxidative stress and stimulating excitotoxic receptors. In preliminary studies on human subjects, ALS subjects had higher median Hcy levels compared to age- and sex-matched controls. Higher Hcy levels were also correlated with a possible marker of disease progression. Finally, a short-term treatment with a high dose of methylcobalamin, which reduces Hcy levels, was effective in improving compound motor action potentials in patients with ALS. In conclusion, several types of evidence show that accumulation of Hcy may increase the risk and progression of motoneuronal degeneration. If this is confirmed, early interventions to decrease Hcy levels may be useful to modify ALS progression and possibly onset.
Link: http://www.ncbi.nlm.nih.gov/pubmed/19551535
Homocysteine, vitamin determinants and neurological diseases.
Abstract
This review focuses on the putative role of hyper-homocysteinemia in the pathogenesis of different diseases affecting the nervous system, including stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, multiple sclerosis and amyotrophic lateral sclerosis. However, a firm pathogenic role of homocysteine in these diseases has never been established. Lowering plasma homocysteine levels trough vitamin therapy failed to prevent vascular diseases. Conversely, normalization of hyper-homocysteinemia caused improvement in patients with cognitive impairment. B vitamin deficiency is the main determinant of homocysteine levels. However, it has been hypothesized that homocysteine might be a mere marker of vitamin deficiency or an indicator of disease rather than a risk factor. A more consistent use of thresholds to define deficiency is needed to recommend routine screening, monitoring and supplementation of B vitamins to ameliorate the prognosis of the above mentioned disorders. To date, data are insufficient to firmly establish which one of the hypotheses made is correct and the question concerning the real meaning of hyper-homocysteinemia in the pathology of the nervous system still remains an intriguing medical dilemma.
Link: http://www.ncbi.nlm.nih.gov/pubmed/20036953
Homocysteine: a casual link with heart failure?
Abstract
Several studies and recent patents have demonstrated that hyperhomocysteinemia (HHCY) is an independent risk factor for congestive heart failure (CHF); it is also correlated to the severity of the disease. In literature there are some data about effects of HHCY on myocardial structure and function in animal models. These studies indicate a direct effect of HCY in promoting reactive myocardial fibrosis and systolic dysfunction, promoting miocardial redox state, endothelial and mithocondryal dysfunction, negative inotropic effect. According to some authors the HHCY is a potential ethiological factor for heart failure while according to others it is just an epiphenomenon without direct effects on myocardium. Nevertheless the literature studies show the relevant involvement of HHCY in CHF and the strong relations between HHCY plasma levels and the severity and prognosis of the disease. Regarding the potential mechanistic role of HHCY in CHF, all of these studies do not provide any mechanistic insights because of their epidemiological nature. Future studies need to explore the exact pathomechanisms of HHCY in CHF.
Link: http://www.ncbi.nlm.nih.gov/pubmed/19910894
Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and treatment recommendations.
Abstract
In Europe, neuropsychiatric diseases currently make up approximately a third of the total burden of disease. In 2004, 27% of the overall population was affected by at least one of the most frequent neuropsychiatric diseases such as Alzheimer’s dementia, Parkinson’s disease, stroke or depression. The annual costs of care exceed those of cancer, cardiovascular conditions and diabetes. In order to delay the onset or course of neurodegenerative diseases, the available potential should be utilized. As well as improving quality of life of patients and relatives, this may reduce the great financial burden caused by neurodegenerative disorders. However, the availability of established drugs or therapeutic agents is very limited. This paper reviews the state of current knowledge as to how homocysteine metabolism is relevant for neurodegenerative and other neuropsychiatric diseases, with particular emphasis on the evidence for prophylactic and therapeutic strategies. In the European countries, many people do not take the recommended daily minimum amount of folate and vitamin B12. Deficiency of these vitamins and secondary changes in the concentrations of associated metabolites, such as methylmalonic acid and homocysteine, may contribute to the onset and progression of neuropsychiatric diseases. This paper reviews the evidence regarding whether substitution of folate and vitamin B12 is beneficial, for example, in cerebrovascular disease, dementia and depression.
Link: http://www.ncbi.nlm.nih.gov/pubmed/19769453
Homocysteine, vitamin B12, folate and cognitive functions: a systematic and critical review of the literature.
Abstract
Elevated serum homocysteine, decreased folate and low vitamin B(12) serum levels are associated with poor cognitive function, cognitive decline and dementia. Despite evidence of an epidemiological association, randomised controlled trials did not provide any clear evidence so far that supplementation with vitamin B(12) and/or folate improves dementia or slows cognitive decline, even though it might normalise homocysteine levels. In this report, we review the current knowledge on the relationship between homocysteine, folate and vitamin B(12) levels and the way their disruption influences cognitive function in adults.
Link: http://www.ncbi.nlm.nih.gov/pubmed/19570123
Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis.
Abstract
BACKGROUND: Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B(12), and related metabolites were associated with prostate cancer risk.
METHODS: Matched case-control study nested within the U.K. population-based Prostate testing for cancer and Treatment (ProtecT) study of prostate-specific antigen-detected prostate cancer in men ages 50 to 69 years. Plasma concentrations of folate, B(12) (cobalamin), holo-haptocorrin, holo-transcobalamin total transcobalamin, and total homocysteine (tHcy) were measured in 1,461 cases and 1,507 controls. ProtecT study estimates for associations of folate, B(12), and tHcy with prostate cancer risk were included in a meta-analysis, based on a systematic review.
RESULTS: In the ProtecT study, increased B(12) and holo-haptocorrin concentrations showed positive associations with prostate cancer risk [highest versus lowest quartile of B(12) odds ratio (OR) = 1.17 (95% confidence interval, 0.95-1.43); P(trend) = 0.06; highest versus lowest quartile of holo-haptocorrin OR = 1.27 (1.04-1.56); P(trend) = 0.01]; folate, holo-transcobalamin, and tHcy were not associated with prostate cancer risk. In the meta-analysis, circulating B(12) levels were associated with an increased prostate cancer risk [pooled OR = 1.10 (1.01-1.19) per 100 pmol/L increase in B(12); P = 0.002]; the pooled OR for the association of folate with prostate cancer was positive [OR = 1.11 (0.96-1.28) per 10 nmol/L; P = 0.2) and conventionally statistically significant if ProtecT (the only case-control study) was excluded [OR = 1.18 (1.00-1.40) per 10 nmol/L; P = 0.02].
CONCLUSION: Vitamin B(12) and (in cohort studies) folate were associated with increased prostate cancer risk.
IMPACT: Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations.
Link: http://www.ncbi.nlm.nih.gov/pubmed/20501771
Does diet affect our mood? The significance of folic acid and homocysteine
Abstract
In recent years, there has been growing interest in the association between national diet and the possibility of developing various mental disorders, as well as between deficiency of such vitamins as, e.g. folic acid, vitamin B12, B6, and others (e.g., omega-3 fatty acids), elevated serum homocysteine level and the functioning of human brain as well as the occurrence of such disorders as dementia, central nervous system vascular disorders and depression.
THE AIM OF THE STUDY: was to present the current state of knowledge about the role of folic acid and homocysteine in the human organism as well as the significance of vitamin deficiency, mainly folic acid and hyperhomocysteinemy for the occurrence of mood disorders.
METHOD: The authors conducted the search of the Internet database Medline (www.pubmed.com) using as key words: depression, mood, homocysteine, vitamin deficiencies: folic acid, B6 and 812 and time descriptors: 1990-2007.
RESULTS: In depression, folate, vitamins B12 and B6, as well as unsaturated omega-3 fatty acids deficiency affects the biochemical processes in the CNS, as folic acid and vitamin B12, participate in the metabolism of S-adenosylmethionine (SAM), a donator of methyl groups, which play a decisive role in the functioning of the nervous system; they are, among others, active in the formation of neurotransmitters (e.g. serotonin), phospholipids that are a component of neuronal myelin sheaths, and cell receptors. The deficiency of the vitamins in question results in hyperhomocysteinemia (the research shows that approximately 45-55% of patients with depression develop significantly elevated serum homocysteine), which causes a decrease in SAM, followed by impaired methylation and, consequently, impaired metabolism of neurotransmitters, phospholipids, myelin, and receptors. Hyperhomocysteinemia also leads to activation of NMDA receptors, lesions in vascular endothelium, and oxidative stress. All this effects neurotoxicity and promotes the development of various disorders, including depression. Vitamins B12 and B6, folic acid and omega-3 fatty acids supplementation is thus important in patients suffering from their deficiency; national diet as a significant factor in prevention of numerous CNS disorders, including depression, is also worth consideration.
Link: http://www.ncbi.nlm.nih.gov/pubmed/19388520
Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials.
Abstract
Plasma total homocysteine (Hcy) has been associated with cardiovascular risk in multiple large-scale epidemiological studies, and it has been considered as an independent risk factor for atherosclerosis. Homocysteine lowering, achieved after the introduction of the folate food fortification programme in North America, was accompanied by an accelerated decline of cardiovascular risk and especially of stroke. Although the initial clinical trials suggested that homocysteine-lowering treatment with folates and B vitamins induces coronary plaque regression, this finding was not confirmed by more recent clinical studies. Under the light of the findings from the recent large randomized clinical trials that failed to document a benefit of Hcy lowering on clinical outcome of patients with atherosclerosis, the role of Hcy as a risk factor and the efficacy of Hcy lowering against atherosclerosis have been questioned. Therefore, better understanding of the mechanisms relating Hcy and Hcy-lowering treatment with vascular function and atherogenesis is crucial, to help us understand why clinical trials failed to show a benefit from Hcy-lowering treatment. Are these therapeutic strategies ineffective because they fail to reduce intracellular Hcy levels and vascular redox state or should Hcy stop being considered as an independent risk factor for atherosclerosis from now on? In this review article, we provide a global approach of the molecular mechanisms relating Hcy with cardiovascular risk and introduce possible mechanistic explanations regarding the inability of clinical trials to detect any clinical benefit from Hcy-lowering treatment in secondary prevention. Finally, we provide clinical recommendations regarding the therapeutic strategies targeting homocysteine in the general population.
Link: http://www.ncbi.nlm.nih.gov/pubmed/19029125
Homocysteine and depression in later life.
Abstract
CONTEXT: The prevalence of depression in later life increases with plasma total homocysteine concentration (tHcy). High tHcy accounts for about 15% of prevalent cases, but observational studies are prone to confounding and bias. Genetic association studies are not prone to the same sources of error and offer an opportunity to explore the consistency and external validity of this association.
OBJECTIVE: To determine if tHcy is causally related to depression in later life.
DESIGN: Cross-sectional study (Health in Men Study), systematic review, and meta-analysis. Patients Community sample of 3752 men aged 70 years or older (Health in Men Study).
MAIN OUTCOME MEASURES: Fifteen-Item Geriatric Depression Scale and self-reported past or current treatment for depression (Health in Men Study).
RESULTS: In the Health in Men Study, the odds ratio (OR) of prevalent depression increased 4% (OR, 1.04; 95% confidence interval [CI], 1.02-1.05) with every unit increase of tHcy (micromoles per liter). The tHcy was 0.19 mg/L higher among participants with the MTHFR C677T TT genotype compared with the CC genotype. The meta-analysis showed that older adults with high tHcy had increased risk of depression (OR, 1.70; 95% CI, 1.38-2.08) and TT carriers were 22% more likely than CC carriers to have current depression or a history of depression (OR, 1.22; 95% CI, 1.01-1.47).
CONCLUSIONS: The triangular association between the MTHFR genotype, tHcy, and depression implies that higher concentrations of tHcy increase the risk of depression and that lowering tHcy by 0.19 mg/L could reduce the odds of depression by about 20%. Confirmatory data from sufficiently powered randomized trials of homocysteine-lowering therapy are now required to test if the relationship between tHcy and depression is truly causal.