Evaluating the therapeutic potential of one-carbon donors in nonalcoholic fatty liver disease

Bakir, Marwa B.; Salama, Mona; Refaat, Rowaida; Ali, Mennatallah A.; Khalifa, Eman; Kamel, Maher A.

doi:10.1016/j.ejphar.2019.01.039

Cited by 22 publications

(14 citation statements)

References 47 publications

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“…Hepatic steatosis, defined as accumulation of excess fat in the liver [ 25 ], occurs when the mechanisms that normally utilize or remove lipids become impaired. Steatosis is the earliest manifestation of alcohol misuse or high caloric intake, but it can also be caused by insulin resistance, malnutrition, anorexia, sleep apnea, or exposure to toxins/drugs such as carbon tetrachloride, diphtheria toxins, aspirin, or tetracyclines [ 26 ]. Prolonged hepatic fat storage eventually results in metabolic dysfunction, inflammation, and advanced forms of liver disease [ 27 , 28 , 29 , 30 ].…”

Section: Disease Prevention By Betaine Administrationmentioning

confidence: 99%

Beneficial Effects of Betaine: A Comprehensive Review

Arumugam

Paal

Donohue

et al. 2021

Biology

135

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Medicinal herbs and many food ingredients possess favorable biological properties that contribute to their therapeutic activities. One such natural product is betaine, a stable, nontoxic natural substance that is present in animals, plants, and microorganisms. Betaine is also endogenously synthesized through the metabolism of choline or exogenously consumed through dietary intake. Betaine mainly functions as (i) an osmolyte and (ii) a methyl-group donor. This review describes the major physiological effects of betaine in whole-body health and its ability to protect against both liver- as well as non-liver-related diseases and conditions. Betaine’s role in preventing/attenuating both alcohol-induced and metabolic-associated liver diseases has been well studied and is extensively reviewed here. Several studies show that betaine protects against the development of alcohol-induced hepatic steatosis, apoptosis, and accumulation of damaged proteins. Additionally, it can significantly prevent/attenuate progressive liver injury by preserving gut integrity and adipose function. The protective effects are primarily associated with the regulation of methionine metabolism through removing homocysteine and maintaining cellular SAM:SAH ratios. Similarly, betaine prevents metabolic-associated fatty liver disease and its progression. In addition, betaine has a neuroprotective role, preserves myocardial function, and prevents pancreatic steatosis. Betaine also attenuates oxidant stress, endoplasmic reticulum stress, inflammation, and cancer development. To conclude, betaine exerts significant therapeutic and biological effects that are potentially beneficial for alleviating a diverse number of human diseases and conditions.

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Section: Disease Prevention By Betaine Administrationmentioning

confidence: 99%

Beneficial Effects of Betaine: A Comprehensive Review

Arumugam

Paal

Donohue

et al. 2021

Biology

135

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“…Symptoms of inflammation, pain (osteoarthritis and fibromyalgia patients), vacuolar myelopathy, liver disease, reperfusion injury, and MD were shown to be attenuated with SAMe supplementation with or without use of added NSAIDS or antidepressants. Furthermore, SAMe supplementation at 800 mg/day was reported to significantly lower serum cholesterol in cardiovascular patients (or at risk for it) [ 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ].…”

Section: Mini Reviews On the Roles Of Dmf Bupropion Same And VImentioning

confidence: 99%

“…( f ) Serum levels of SAMe in aggressive and manic patients normally exceed the standard range (see text) and SAMe supplementation for these patients is contraindicated. ( g ) S -adenosylmethionine 1,4-butane disulfonate is found in OTC oral supplements [ 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ].…”

Section: Figurementioning

confidence: 99%

Proposed Neuroimmune Roles of Dimethyl Fumarate, Bupropion, S-Adenosylmethionine, and Vitamin D3 in Affording a Chronically Ill Patient Sustained Relief from Inflammation and Major Depression

Sachinvala¹,

Teramoto

Stergiou

2020

Brain Sciences

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We had discussed earlier that, after most of the primary author’s multiple sclerosis (MS) symptoms were lessened by prior neuroimmune therapies, use of dimethyl fumarate (DMF) gradually subdued his asthma and urticaria symptoms, as well as his MS-related intercostal cramping; and bupropion supplemented with S-adenosylmethionine (SAMe) and vitamin D3 (vit-D3) helped remit major depression (MD). Furthermore, the same cocktail (bupropion plus supplements), along with previously discussed routines (yoga, meditation, physical exercises, and timely use of medications for other illnesses), continued to subdue MD during new difficulties with craniopharyngioma, which caused bitemporal vision loss; sphenoid sinus infections, which caused cranial nerve-VI (CN6) palsy and diplopia; and through their treatments. Impressed by the benefit the four compounds provided, in this manuscript, we focus on explaining current neuroimmune literature proposals on how: (1) DMF impedes inflammation, oxidative stress, and cell death in CNS and peripheral tissues; (2) Bupropion curbs anxiety, MD, and enhances alertness, libido, and moods; (3) SAMe silences oxidative stress and depression by multiple mechanisms; and (4) Vit-D3 helps brain development and functioning and subdues inflammation. we realize that herein we have reviewed proposed mechanisms of remedies we discovered by literature searches and physician assisted auto-experimentation; and our methods might not work with other patients. We present our experiences so readers are heartened to reflect upon their own observations in peer-reviewed forums and make available a wide body of information for the chronically ill and their physicians to benefit from.

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“…Betaine donates a methyl group for the remethylation of homocysteine to methionine, which further produces SAM through adenosylation. Rodents with high‐fat diet–induced NAFLD exhibited disrupted one‐carbon metabolism, indicated by a decreased SAM concentration and an increased homocysteine concentration as well as a decreased global DNA methylation level in the liver . Methyl‐donor (methionine, choline, folic acid, and betaine) depletion diets are used to establish rodent models of NASH and HCC, which also have been associated with decreased global DNA methylation .…”

Section: Introductionmentioning

confidence: 99%

“…Methyl‐donor (methionine, choline, folic acid, and betaine) depletion diets are used to establish rodent models of NASH and HCC, which also have been associated with decreased global DNA methylation . In contrast, methyl‐donor repletion (via betaine, choline, and folic acid supplementation) reversed global DNA hypomethylation in the liver and attenuated NAFLD in these rodent models . Although recent studies have investigated DNA methylation and one‐carbon metabolites in animal models of NAFLD, the relationships of these factors with the severity of liver histology in patients with NAFLD remain uncertain.…”

Section: Introductionmentioning

confidence: 99%

Association of Hepatic Global DNA Methylation and Serum One‐Carbon Metabolites with Histological Severity in Patients with NAFLD

Lai

Chen

Ding

et al. 2019

Obesity

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Objective Clinical relevance of global DNA methylation and one‐carbon metabolite levels with histological severity remains uncertain in patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to evaluate hepatic global DNA methylation and serum one‐carbon metabolite concentrations in patients with NAFLD and the possible associations of these parameters with liver histology. Methods Liver biopsies from 18 control participants and 47 patients with NAFLD were evaluated. Results The hepatic global DNA methylation level was significantly lower in the NAFLD group than in the control group among participants with overweight. Participants with moderate inflammation and mild fibrosis had significantly lower levels of global DNA methylation than those without these characteristics. Participants with borderline nonalcoholic steatohepatitis had significantly lower global DNA methylation levels than controls. The hepatic global DNA methylation level tended to decrease with the increasing hepatic inflammation grade and disease progression. The NAFLD group had a significantly higher serum homocysteine concentration than the control group among participants with overweight. This level tended to increase with increasing hepatic steatosis grade and disease progression. Conclusions Patients with NAFLD exhibited lower hepatic levels of global DNA methylation and elevated serum homocysteine concentrations, which are associated with the histological severity of NAFLD.

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Evaluating the therapeutic potential of one-carbon donors in nonalcoholic fatty liver disease

Cited by 22 publications

References 47 publications

Beneficial Effects of Betaine: A Comprehensive Review

Beneficial Effects of Betaine: A Comprehensive Review

Proposed Neuroimmune Roles of Dimethyl Fumarate, Bupropion, S-Adenosylmethionine, and Vitamin D3 in Affording a Chronically Ill Patient Sustained Relief from Inflammation and Major Depression

Association of Hepatic Global DNA Methylation and Serum One‐Carbon Metabolites with Histological Severity in Patients with NAFLD

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