Links between depression and arginine levels

People suffering from major depressive disorder, MDD, have reduced arginine levels, a new study from the University of Eastern Finland shows. Arginine is an amino acid which the body uses to produce nitric oxide. Nitric oxide is a nervous system and immune defence mediator, and it also plays a role in vascular regulation.

The global arginine bioavailability ratio, GABR, is an indicator of the body's arginine levels, and the ratio has previously been used to measure the body's capacity to produce nitric oxide. Reduced arginine bioavailability is also known to be an independent risk factor of cardiovascular diseases. The study shows that people suffering from MDD have reduced arginine bioavailability.

"It is possible that depression-induced inflammatory responses lead to reduced arginine levels. This may result in insufficient production of nitric oxide for the needs of the nervous system and circulation. However, we don't know yet what exactly causes reduced arginine bioavailability in people with depression," says Doctoral Student Toni Ali-Sisto, the lead author of the study.

The research carried out by the University of Eastern Finland and Kuopio University Hospital involved 99 adults with diagnosed major depressive disorder and 253 non-depressed controls. The concentrations of three amino acids, namely arginine, citrulline and ornithine, were analysed from their fasting glucose samples, and this data was used to calculate their GABRs. Symmetric and asymmetric dimethylarginine concentrations were also measured, as they both play a role in the production of nitric oxide.

The findings were then compared between the depressed and the non-depressed controls. The study also analysed whether these concentrations changed in people with depression during a follow-up of eight months, and whether remission of depression had an effect on the concentrations. The study shows that people with depression have reduced arginine bioavailability, this doesn't mean that taking an arginine supplement would protect against depression.

People with depression had weaker arginine bioavailability than their non-depressed controls. The study did not find significant differences in the symmetric and asymmetric dimethylarginine concentrations. The use of anti-depressants or anti-psychotics did not affect the concentrations, either. Contrary to the researchers' expectations, there were no clear differences in the concentrations measured from people who had recovered from depression and people who remained depressed. Arginine bioavailability was slightly higher in people who had recovered from depression than in people who remained depressed.
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Using mouthwash increases the risk of obesity and diabetes

Using mouthwash twice a day significantly raises the risk of obesity and developing type 2 diabetes, according to a new study. Swilling with the anti-bacterial fluid could be killing beneficial microbes which live in the mouth and protect against the conditions. People who used the product twice a day were around 55 percent more likely to develop diabetes or dangerous blood sugar spikes.

Popular mouthwash solutions include ingredients that kill good and bad bacterial. Most of these antibacterial ingredients in mouthwash are not selective- they do not target specific oral bacteria-instead, these ingredients can act on a broad range of bacteria.
Researchers looked at overweight people who were at risk of developing diabetes. Over the study period, around 17 per cent developed diabetes or pre-diabetes, but that rose to 20 per cent for those using mouthwash once a day, and 30 per cent for those using it in the morning and evening.

Helpful bacteria in the mouth can protect against obesity and diabetes, as it helps the body produce nitric oxide. This important molecule helps trillions of our cells to communicate with each other by transmitting signals throughout the entire body and regulates insulin levels and our metabolism. Commonly-used mouthwashes typically contain powerful bacteria-killing formulas including cetylpyridinium chloride, chlorhexidine, triclosan, alcohol, fluoride, peroxide and essential oils. However, the researchers warn killing off good helpful bacteria also makes room for harmful bacteria to thrive.
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Genes and environment can increase the risk of congenital heart defects

Infants of mothers with diabetes have increased risk of congenital heart defects. Such developmental defects are likely caused by a combination of genetic and environmental factors. The molecular mechanisms by which maternal diabetes disrupts normal heart development in genetically susceptible individuals remain unclear.

The Cardiovascular Research describe a gene-environment interaction resulting in congenital heart defects in both mouse and fly model systems. Interaction between two genes, Endothelial Nitric Oxide Synthase and Notch1, would result in more severe types of congenital heart defects in animal models. Diabetes is known to be associated with decreased nitric oxide levels in blood vessels.

Maternal diabetes, in combination with a mutation in Notch1, would result in a higher risk of congenital heart disease.
Researchers showed that maternal hyperglycemia reduces the chromatin accessibility of the Endothelial Nitric Oxide Synthase gene, resulting in decreased nitric oxide production.

This loss of nitric oxide is associated with an increase in expression of Jarid2, a known repressor of the Notch1 gene. This directly inhibited Notch1 expression to levels below a critical threshold necessary for normal heart development. This study lends support to a gene-environment interaction model where maternal hyperglycemia raises the risk of congenital heart defects by reducing Notch1 expression.

The results reveal the epigenetic machinery by which maternal hyperglycemia disrupts the Nitric Oxide and Notch1 signaling pathways, leading to congenital heart defects. Infants that are exposed to hyperglycemia develop a congenital heart defect, which supports the idea that there are genetically susceptible individuals.
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