Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics

Fernández-Rodríguez, Camino; González‐Reimers, Emilio; Quintero-Platt, Geraldine; Vega-Prieto, Marı́a José de la; Pérez-Hernández, Onán; Martín-González, Candelaria; Espelosín-Ortega, Elisa; Romero-Acevedo, Lucía; Santolaria-Fernández, Francisco

doi:10.1093/alcalc/agw031

Cited by 8 publications

(8 citation statements)

References 37 publications

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“…Hyperhomocysteinaemia and vitamin B12 deficiency are often detected in patients affected with diseases associated with neuropathy such as diabetes, 66 alcoholism, 67 Parkinson’s disease (treated with L‐dopa), 68 or HIV infection 69 . Vitamin B12 deficiency could be a modifiable risk factor for neuropathy in those patients.…”

Section: Discussionmentioning

confidence: 99%

Association between neuropathy and B‐vitamins: A systematic review and meta‐analysis

Stein

Geisel

Obeid

2021

Euro J of Neurology

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Background Peripheral neuropathy (PN) is common in patients with diseases that are in turn associated with deficiency of the B‐vitamins, and vitamin treatment has shown mixed results. Methods This systematic review and meta‐analysis studied the association between PN/pain and B‐vitamin biomarkers and investigated whether vitamin treatment can ameliorate the symptoms. PubMed and Web of Science were searched according to the study protocol. Results A total of 46 observational and seven interventional studies were identified and included in the data synthesis. The presence of PN was associated with lowered B12 levels (pooled estimate [95% CIs] = 1.51 [1.23–1.84], n = 34, Cochran Q Test I2 = 43.3%, p = 0.003) and elevated methylmalonic acid (2.53 [1.39–4.60], n = 9, I2 = 63.8%, p = 0.005) and homocysteine (3.48 [2.01–6.04], n = 15, I2 = 70.6%, p < 0.001). B12 treatment (vs. the comparators) showed a non‐significant association with symptom improvement (1.36 (0.66–2.79), n = 4, I2 = 28.9%). Treatment with B1 was associated with a significant improvement in symptoms (5.34 [1.87–15.19], n = 3, I2 = 64.6%, p = 0.059). Analysis of seven trials combined showed a non‐significant higher odds ratio for improvement under treatment with the B‐vitamins (2.58 [0.98–6.79], I2 = 80.0%, p < 0.001). Conclusions PN is associated with lowered plasma vitamin B12 and elevated methylmalonic acid and homocysteine. Overall, interventional studies have suggested that B‐vitamins could improve symptoms of PN. Available trials have limitations and generally did not investigate vitamin status prior to treatment. Well‐designed studies, especially in non‐diabetes PN, are needed. This meta‐analysis is registered at PROSPERO (ID: CRD42020144917).

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Section: Discussionmentioning

confidence: 99%

Association between neuropathy and B‐vitamins: A systematic review and meta‐analysis

Stein

Geisel

Obeid

2021

Euro J of Neurology

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“…Both conditions were significantly more frequent in the subgroup of LHON patients with B12 deficiency. Patients with excessive alcohol consumption are known to represent a high-risk group for vitamin deficiency, including B12 deficiency [ 47 ]. Using multivariate analysis, we confirmed that excessive alcohol consumption is a significant predictor for LHON disease status and for B12 deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, we may have underestimated the true prevalence of B12 deficiency in the LHON subgroup with excessive alcohol consumption: Not only serum B12 may be falsely elevated in subjects with excessive alcohol consumption [ 47 – 50 ], but also they present with hyperhomocysteinemia [ 47 ]. It is unclear whether subjects with excessive alcohol consumption, normal serum B12, and increased tHCy have a true vitamin B12 deficiency.…”

Section: Discussionmentioning

confidence: 99%

Vitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study

Zibold

Livonius

Kolářová

et al. 2022

Orphanet J Rare Dis

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Background Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, frequently resulting in acute or subacute severe bilateral central vision loss. Vitamin B12 deficiency is also a known cause of optic neuropathy through mitochondrial dysfunction. Here we evaluated the prevalence and clinical significance of vitamin B12 deficiency in a large cohort of LHON patients and asymptomatic mutation carriers from a tertiary referral center. Methods From the Munich LHON prospective cohort study, participants included all LHON patients and asymptomatic LHON mutation carriers, who were recruited between February 2014 and March 2020 and consented to participate. Neurological, general, and ophthalmological examinations were regularly performed, as were laboratory tests. Vitamin B12 deficiency was diagnosed if serum vitamin B12 was below 201 pg/mL, or if 201–339 pg/mL plus low serum holotranscobalamin or elevated serum methylmalonic acid or elevated total plasma homocysteine. Results We analyzed 244 subjects, including 147 symptomatic LHON patients (74% males) and 97 asymptomatic mutation carriers (31% males). Median age at study baseline was 34 years (range 5–82 years). The prevalence of vitamin B12 deficiency was higher for LHON mutation carriers than for the general population in all age categories. This was statistically significant for the LHON mutation carriers under 65 years (21% vs. 5–7%, p = 0.002). While vitamin B12 deficiency prevalence was not statistically different between LHON patients and asymptomatic mutation carriers, its clinical correlates, e.g., macrocytosis and polyneuropathy, were more frequent in the subgroup of LHON patients. Excessive alcohol consumption was a significant predictor of vitamin B12 deficiency (p < 0.05). Conclusions The high prevalence of vitamin B12 deficiency in LHON mutation carriers, both asymptomatic mutation carriers and LHON patients, highlights the need for regular vitamin B12 screening in this population, in order to ensure early treatment, aiming for better outcomes. Our study is not conclusive regarding vitamin B12 deficiency as determinant for disease conversion in LHON, and further research is warranted to disentangle the role of vitamin B12 in the pathophysiology and prognosis of LHON.

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“…3 Higher values, up to 80%, were reported when brain computed tomography (CT) was blindly evaluated by an expert radiologist. 4 Brain atrophy in alcoholics mainly depends on white matter atrophy, 5 although gray matter atrophy, at least affecting the frontal lobe, has also been described. 6 These changes are associated with the amount of ethanol consumed 7,8 and are partially reversible with abstinence.…”

Section: Introductionmentioning

confidence: 99%

Brain-derived neurotrophic factor among patients with alcoholism

et al. 2020

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Abstract Background: Brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and in the protection against oxidative damage and neuronal apoptosis. After exercise, there is an increased expression of this myokine, especially in skeletal muscle and brain. Low BDNF levels have been described in neurodegenerative diseases. Alcoholics show both muscle atrophy and brain atrophy. Thus, this study was performed in order to analyze serum BDNF levels among alcoholics and their associations with brain atrophy and muscle strength. Methods: Serum BDNF values were determined to 82 male alcoholics and 27 age-matched controls, and compared with handgrip strength, with the presence of brain atrophy, assessed by computed tomography, and with the intensity of alcoholism and liver function derangement. Results: BDNF levels and handgrip strength were significantly lower among patients. Handgrip strength was correlated with BDNF values, both in the whole population and in alcoholics, especially in patients over 59 years of age. BDNF was poorly related to liver dysfunction but showed no relationship with brain atrophy or age. Conclusion: Chronic alcoholics show decreased BDNF serum levels that are related to muscle function impairment rather than to age, brain atrophy, liver dysfunction, or the amount of ethanol consumed.

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Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics

Cited by 8 publications

References 37 publications

Association between neuropathy and B‐vitamins: A systematic review and meta‐analysis

Association between neuropathy and B‐vitamins: A systematic review and meta‐analysis

Vitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study

Brain-derived neurotrophic factor among patients with alcoholism

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