Nutrients in Energy and One-Carbon Metabolism: Learning from Metformin Users

Luciano-Mateo, Fedra; Hernández-Aguilera, Anna; Cabré, Noemí; Camps, Jordi; Fernández-Arroyo, Salvador; López‐Miranda, José; Menendez, Javier A.; Joven, Jorge

doi:10.3390/nu9020121

Cited by 35 publications

(29 citation statements)

References 159 publications

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“…Cheng et al [ 42 ] reported an interaction between PON1 55 polymorphism and several single nucleotide polymorphisms related to homocysteine and folate metabolism. An explanation could be that the folate cycle regulates the availability of methyl groups through the sequential conversion of methionine to S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine and, hence, influences epigenetic modifications of DNA [ 43 ]. In addition, Stevens et al [ 39 ] reported that the M allele of PON1 55 polymorphism is associated with increased risk of BC only in patients using nonsteroidal anti-inflammatory drugs (NSAIDs).…”

Section: Discussionmentioning

confidence: 99%

Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in breast cancer patients

et al. 2017

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Paraoxonase-1 (PON1) is an intra-cellular antioxidant enzyme found also in the circulation associated with high-density lipoproteins. The activity of this enzyme has been shown to be decreased in breast cancer (BC) patients. The aims of our study were to investigate the changes produced by radiotherapy (RT) on activity and concentration of serum PON1 in BC patients, and to evaluate the observed variations in relation to clinical and pathological characteristics of patients and tumors, and the response to treatment. We studied 200 women with BC who were scheduled to receive RT following excision of the tumor. Blood for analyses was obtained before and after the irradiation procedure. The control group was composed of 200 healthy women. Relative to control, BC patients had significantly lower serum PON1 activities pre-RT, while PON1 concentrations were at similar levels. RT was associated with a significant increase in serum PON1 activities and concentrations. We observed significant differences in serum PON1 concentrations post-RT between patients with luminal A or luminal B tumors. Serum PON1 concentration post-RT was markedly lower in BC patients with metastases. We conclude that benefit from RT accrues to the BC patients not only through its direct effect on cancer cells but also indirectly by improving the organism’s anti-oxidant defense mechanisms. In addition, our preliminary evidence suggests that the measurement of serum PON1 concentration post-RT could be an efficient prognostic biomarker, and may be used as an index of the efficacy of the RT.

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Section: Discussionmentioning

confidence: 99%

Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in breast cancer patients

et al. 2017

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“…AMPK activation may disrupt embryo gene expression – in particular inhibit Pax3 (paired box 3) expression, a gene involved in neural tube closure – with resultant increased risk of neural tube defects. AMPK also induces changes in several bioactive metabolites connected to transcriptional regulators [ 83 ]. Because metformin increases AMPK activation, its effects on offspring need to be evaluated.…”

Section: Concerns With Fetal Exposure To Metforminmentioning

confidence: 99%

“…Another important concern stems from the effect of metformin on 1-C pathways. Metformin has been demonstrated to have an antifolate effect similar to some chemotherapeutic drugs [ 83 ].…”

Section: Concerns With Fetal Exposure To Metforminmentioning

confidence: 99%

Metformin in the management of diabetes during pregnancy and lactation

Priya

Kalra

2018

DIC

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This review explores the current place of metformin in the management of gestational diabetes (GDM) and type 2 diabetes during pregnancy and lactation. The rationale and basic pharmacology of metformin usage in pregnancy is discussed along with the evidence from observational and randomized controlled trials in women with GDM or overt diabetes. There seems to be adequate evidence of efficacy and short-term safety of metformin in relation to maternal and neonatal outcomes in GDM, with possible benefits related to lower maternal weight gain and lower risk of neonatal hypoglycemia and macrosomia. Additionally, metformin offers the advantages of oral administration, convenience, less cost and greater acceptability. Metformin may, therefore, be considered in milder forms of GDM where glycemic goals are not attained by lifestyle modification. However, failure rate is likely to be higher in those with an earlier diagnosis of GDM, higher blood glucose, higher body mass index (BMI) or previous history of GDM, and insulin remains the cornerstone of pharmacological treatment in such cases. The use of metformin in type 2 diabetes has been assessed in observational and small randomized trials. Metformin monotherapy in women with overt diabetes is highly unlikely to achieve glycemic targets. Hence, the use should be restricted as adjunct to insulin and may be considered in women with high insulin dose requirements or rapid weight gain. There is clearly a need for more clinical trials to assess the effect of combined insulin plus metformin therapy in pregnancy with type 2 diabetes. Additionally, there is a paucity of data on long-term effects in offspring exposed to metformin in utero. It is imperative to further explore its impact on offspring as metformin has significant transplacental transfer and has the potential to impact the programming of the epigenome. Therefore, caution must be exercised when prescribing metformin in pregnant women. More research is clearly needed before metformin can be considered as standard of care in the management of diabetes during pregnancy.

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“…AMPK regulates several processes including gene expression and mechanistic target of rapamycin (mTOR)-induced effects on protein synthesis [ 27 , 39 – 41 ]. In addition, there are separated, but nonredundant mitochondrial and cytosolic pathways that generate one-carbon intermediates that can be inhibited by metformin, mimicking the ‘methyl folate trap’ that can occur during vitamin B 12 deficiency [ 28 , 42 , 43 ]. This can lead to methionine deprivation, decreased glutathione (reduced, oxidised disulphide and trisulphide forms), increased homocysteine, and decreased de novo synthesis of purines and pyrimidines [ 28 , 42 ].…”

Section: Does Recent Basic Science Explain How Use Of Metformin In Prmentioning

confidence: 99%

Metformin use in pregnancy: promises and uncertainties

Lindsay

Loeken

2017

Diabetologia

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Metformin has been prescribed in pregnancy for over 40 years; for much of this time, use has been limited both in numbers and geographically, and the evidence base has been confined to observational studies. In early years, perceived safety concerns and lack of availability of the drug in many countries acted as a barrier to use. More recently, RCTs have begun to examine the role of metformin in pregnancy in much-needed detail. However, this evidence base has been interpreted differently in different countries, leading to very wide variation in its current application in pregnancy. In this short review, we will discuss the history of metformin in pregnancy and highlight some of the key clinical trials. We will then consider some of the remaining controversies associated with metformin use in pregnancy, most important of these being the potential for long-term ‘programming’ effects on the fetus as a result of metformin being able to cross the placenta. We will also consider clinical situations where metformin might be avoided. Finally, we will discuss some future directions for this drug as it reaches its sixtieth anniversary.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-017-4351-y) contains a slide of the figure for download, which is available to authorised users.

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Nutrients in Energy and One-Carbon Metabolism: Learning from Metformin Users

Cited by 35 publications

References 159 publications

Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in breast cancer patients

Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in breast cancer patients

Metformin in the management of diabetes during pregnancy and lactation

Metformin use in pregnancy: promises and uncertainties

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