Efficacy of Multivitamin Supplementation Containing Vitamins B6 and B12 and Folic Acid as Adjunctive Treatment with a Cholinesterase Inhibitor in Alzheimer's Disease: A 26-Week, Randomized, Double-Blind, Placebo-Controlled Study in Taiwanese Patients

Sun, Yu; Lu, Chien-Jung; Chien, Kuo‐Liong; Chen, Sien-Tsong; Chen, Rong-Chi

doi:10.1016/j.clinthera.2007.10.012

Cited by 99 publications

(121 citation statements)

References 40 publications

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“…There has been a general optimism that corrections of hyperhomocysteinemia by supplementation with folate, vitaminB12 and vitamin B6 would be beneficial in preventing or halting AD progression [126]. However, several interventional epidemiological studies have shown that while hyperhomocysteinemia can be reversed by supplementation with vitamin B12, folate, pyridoxine etc., the dementia is not improved [127,128]. Since homocysteine is a known vascular risk factor, it is likely that hyperhomocysteinemia probably contributes to vascular component of AD pathology.…”

Section: Hyperhomocysteinemiamentioning

confidence: 99%

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

Chakrabarti¹,

Khemka²,

Banerjee³

et al. 2015

Aging and disease

112

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Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, proinflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors.

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Section: Hyperhomocysteinemiamentioning

confidence: 99%

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

Chakrabarti¹,

Khemka²,

Banerjee³

et al. 2015

Aging and disease

112

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“…One randomized, double blind, placebo controlled study of vitamins B6 and B12, and folate supplementation in mild to moderately demented AD patients who had normal B12 and folate levels at baseline, and were concomitantly treated with a ChEI found no significant group differences in ADAS-Cog or functional activities after 6 months of treatment [41]. In contrast, another randomized, double blind, placebo controlled trial of folate supplementation in 57 demented AD patients concomitantly treated with a ChEI found significant group differences in the Instrumental Activities of Daily Living and Social Behavior scores of the National Institute of Clinical Excellence scale but no group differences between Mini-Mental State Examination scores [42].…”

Section: Possible Interaction Effects Between Cfln Memantine and Chmentioning

confidence: 99%

CerefolinNAC Therapy of Hyperhomocysteinemia Delays Cortical and White Matter Atrophy in Alzheimer’s Disease and Cerebrovascular Disease

Shankle¹,

Hara²,

Barrentine

et al. 2016

JAD

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Abstract. We examined whether using a medical food therapy for hyperhomocysteinemia (HHcy) in patients with Alzheimer's disease (AD) or cognitive impairment due to cerebrovascular disease (CVD) with Cerefolin ® /CerefolinNAC ® (CFLN: Lmethylfolate, methylcobalamin, and N-acetyl-cysteine) slowed regional brain atrophy. Thirty HHcy patients with AD and related disorders (ADRD) received CFLN (HHcy+CFLN: duration [ ± σ] = 18.6 ± 16.1 months); a sub-sample of this group did not receive CFLN for varying periods of time (HHcy+NoCFLN: duration [ ± σ] = 12.6 ± 5.6 months). Thirtyseven NoHHcy patients with ADRD did not receive CFLN (NoHHcy+NoCFLN: duration [ ± σ] = 13.3 ± 17.7 months). No participant took supplemental B vitamins. Regional brain volumes were measured at baseline and end of study, and covariate-adjusted rates of hippocampal, cortical, and forebrain parenchymal (includes white matter) atrophy were predicted. The HHcy+CFLN group's hippocampal and cortical atrophy adjusted rates were 4.25 and 11.2 times slower than those of the NoHHcy+NoCFLN group (p < 0.024). The HHcy+CFLN group's forebrain parenchyma atrophy rate was significantly slower only for CVD; the rate of slowing was proportional to the degree of homocysteine lowering (p < 0.0001). CFLN was associated with significantly slowed hippocampal and cortical atrophy rates in ADRD patients with HHcy, and forebrain parenchymal atrophy rates in CVD patients with HHcy. The present results should be further validated.

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“…Likewise thrombotic disorders, the outcomes of two recent randomized placebo controlled trials are however disappointing. Sun et al performed a randomized, double-blind, placebo-controlled study in Taiwanese patients with mild to moderate Alzheimer ' s dementia, and found that although a 26-week multivitamin supplement containing vitamins B6, B12 and folic acid was effective to decrease Hcy concentrations, no signifi cant differences in cognition or performance of activities of daily living function were found between multivitamin and placebo (30) . In the latter study, Kwok et al found the concentration of Hcy was reduced to nearly 9 μ mol/L in a group of mild to moderate Alzheimer's disease patients supplemented with methylcobalamin and folic acid for 24 months as compared with a placebo group, but no signifi cant difference in any of the neuropsychological scores could be recorded between supplement group and placebo (31) .…”

Section: Where Do We Go From Here ?mentioning

confidence: 99%

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

Lippi

Plebani

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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Homocysteine is a sulfur-containing amino acid, which is synthesized from the precursor methionine through a multi-step process, and then reconverted to methionine or catabolyzed into cysteine. The presence of vitamin B9 (folic acid), vitamin B6 (pyridoxine) and vitamin B12 (cobalamin) is essential in homocysteine metabolism, wherein defi ciency of one or more of these nutrients is associated with various degree of hyperhomocysteinemia. There is little doubt that hyperhomocysteinemia is associated with several human disorders, such as cardiovascular disease, neurodegenerative disorders, pregnancy complications and fractures, so that its measurement might be useful for risk assessment. Nevertheless, several randomized homocysteine-lowering therapy trials have failed to show that supplementation with vitamins B substantially modifi es (and -more importantly -improves) the end points and the related outcomes. According to the current state of scientifi c knowledge, it seems thus reasonable to conclude that lowering homocysteine alone is probably insuffi cient to mitigate the risk of thromboembolic, cardiovascular and neurodegenerative disorders inasmuch as this bizarre amino acid acts in strict synergy with other probably more powerful risk factors. Several lines of evidence suggest, however, that its measurement may be helpful for identifying subjects at greater risk of disease, who may thus benefi t from a more aggressive treatment of other modifi able risk factors, as recently shown by result of the 5-year Fenofi brate Intervention and Event Lowering in Diabetes (FIELD) trial.

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Efficacy of Multivitamin Supplementation Containing Vitamins B6 and B12 and Folic Acid as Adjunctive Treatment with a Cholinesterase Inhibitor in Alzheimer's Disease: A 26-Week, Randomized, Double-Blind, Placebo-Controlled Study in Taiwanese Patients

Cited by 99 publications

References 40 publications

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

CerefolinNAC Therapy of Hyperhomocysteinemia Delays Cortical and White Matter Atrophy in Alzheimer’s Disease and Cerebrovascular Disease

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

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