Medical Bulletin 17/ July/ 2024

In a recent study published in the journal Advances in Nutrition, scientists examined whether different measures of magnesium levels, including biomarkers, dietary intake, and supplements, were associated with cognitive health and neurological functioning in adults.

Dementia in older adults significantly contributes to disability, health burdens, and mortality, affecting memory, behavior, and daily activities. With over 55 million people worldwide diagnosed, the prevalence and healthcare costs are expected to rise due to the aging population.

Targeting modifiable risk factors like stress, depression, vascular health, and lifestyle is crucial to reducing dementia's incidence and progression. Electrolytes, particularly magnesium, are vital for neurological health. Magnesium deficiency has been linked to memory impairments and Alzheimer’s disease, though findings from longitudinal studies remain inconsistent.

Magnesium supports neuronal health by reducing inflammation and oxidative damage and preserving the integrity of the blood-brain barrier. It inhibits the activity of the N-methyl-D-aspartate (NMDA) receptor and decreases calcium influx, thereby reducing excitotoxic damage. Additionally, magnesium is crucial for maintaining myelinated axons and the myelin sheaths on neurons.

Studies on animal models have demonstrated that magnesium deficiency is linked to memory impairments associated with hippocampal activity. Additionally, oral magnesium administration has been shown to reduce neuroinflammation.

The present study involves adults over 18 years of age that examined the association between magnesium in the forms of biomarkers, dietary intake or supplements, and cognitive outcomes measured in diagnoses or tests.

The researchers extracted data on magnesium exposure, participant descriptions, association measures, and cognitive outcomes. They detailed the form of magnesium exposure, including the units and assessment methods used in each study. They also used three models to evaluate the association between magnesium exposures and cognitive outcomes.

The study found a U-shaped association between serum magnesium levels and cognitive impairments and dementia. An optimal serum magnesium level of 0.085 millimoles per liter was linked to the lowest dementia risk.

The study found unclear results regarding the impact of different types of magnesium on cognitive health. The review and meta-analysis highlighted a lack of strong evidence linking magnesium exposure to cognitive outcomes. Therefore, more detailed and long-term studies are needed to understand how various sources of magnesium affect cognitive health over time.

Reference: Chen, F., Wang, J., Cheng, Y., Li, R., Wang, Y., Chen, Y., Scott, T., & Tucker, K. L. (2024). Magnesium and Cognitive Health in Adults: A Systematic Review and Meta-Analysis. Advances in Nutrition, 100272.DOI:10.1016/j.advnut.2024.100272, https://www.sciencedirect.com/science/article/pii/S2161831324001066

According to new research from the University of Michigan, a network of proteins found in the central nervous system could be leveraged to enhance the effectiveness and minimize the side effects of popular diabetes and weight-loss medications.

The study, published in the Journal of Clinical Investigation, focused on two proteins, melanocortin 3 and melanocortin 4, primarily located on the surface of neurons in the brain.

These proteins play a central role in regulating feeding behavior and maintaining the body's energy balance.Melanocortin 3 and 4 influence everything from sensing long-term energy stores to processing gut signals about short-term satiety.

GLP-1 agonists, such as semaglutides (e.g., Ozempic) and tirzepatides (e.g., Mounjaro), have gained attention for effectively treating type 2 diabetes, obesity, heart disease, and potentially addiction. These drugs mimic a natural hormone produced by the gut when full, signaling the brain to reduce feeding behavior.

In the study, researchers tested the effects of several hormones that reduce food intake in the mouse models and discovered that modifying the melanocortin system made mice more responsive to GLP-1 drugs and other hormones influencing feeding behavior. Mice treated with a combination of a GLP-1 drug and an MC4R agonist or MC3R antagonist experienced up to five times more weight loss and reduced feeding compared to those receiving only GLP-1 drugs.

The researchers also measured brain activity in areas associated with nausea from GLP-1 drugs and found no increased activation when these drugs were combined with alterations to the melanocortin system. However, priming melanocortin neurons significantly boosted GLP-1 drug activation in hypothalamic feeding centers.

The findings suggested that combining GLP-1 drugs with an MC4R agonist could increase the drugs' effectiveness by up to fivefold without enhancing side effects. This approach could allow patients sensitive to side effects to take lower doses or improve outcomes in those unresponsive to current dosages. Further drug development and clinical testing are needed to advance this strategy.

Although this research has only been conducted in mouse models, researchers remain optimistic that the results will translate effectively to humans.

"The melanocortin system is highly conserved in humans. Everything we've observed in the mouse over the past decades studying these proteins has also been found in humans, so I suspect that these results would also be translatable to patients,” said Cone, director of the U-M Life Sciences Institute.

Reference: Roger D. Cone, et al.; Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice; Journal of Clinical Investigation; Volume 134, Issue 14 on July 15, 2024; 134(14):e178250. https://doi.org/10.1172/JCI178250.

In a recent study published in The Journal of Nutrition, researchers explored the effects of low- and high-glycemic-index (GI) Mediterranean-style (MED) healthy eating patterns (HEPs) on sleep and health-related quality of life.

Health-related quality of life strongly predicts morbidity and mortality, making it a crucial measure for evaluating the effects of interventions. Evidence indicates that low HRQoL is associated with higher cardiometabolic risks. The 36-item short-form health survey (SF-36) is commonly used to assess HRQoL. Additionally, sleep is an important lifestyle factor linked to both cardiometabolic health and HRQoL.

The glycemic index (GI) of food indicates its carbohydrate quality, with glycemic variability reflecting blood glucose fluctuations. Researchers previously reported that the GI of a Mediterranean-style healthy eating pattern (MED-HEP) influences glycemic variability and postprandial glucose response.

Researchers investigated the effects of low- and high-GI Mediterranean-style healthy eating patterns (MED-HEPs) on sleep and health-related quality of life (HRQoL) in individuals with metabolic syndrome.

Participants followed a controlled weight-maintenance diet based on MED-HEPs, with either high or low GI, for the intervention period. Sleep and HRQoL were assessed using questionnaires at baseline and during the final two weeks of the intervention. During the baseline period, participants consumed their regular diets. Both groups had identical fibre and carbohydrate amounts, but the GI differed due to variations in starch sources.

The results showed that 57% of participants had poor sleep quality, and 18% reported excessive daytime sleepiness. Both groups increased their intake of protein, fiber, carbohydrates, and energy, while reducing fat and alcohol consumption. The intervention led to HRQoL improvements, particularly in the role of physical and vitality domains for the low-GI group. No significant differences were found between the groups in other HRQoL domains.

Both groups showed improvements in general health and vitality from baseline to post-intervention. Sleep quality did not differ significantly between groups, although both experienced better sleep latency and reduced daytime dysfunction.

The findings revealed that a low-GI MED-HEP resulted in modest improvements in specific HRQoL domains, such as vitality and physical role, relative to a high-GI MED-HEP; furthermore, there were no significant differences in sleep indices between groups.

Reference: Hjort A, Bergia RE, Vitale M, et al. Low- vs high-glycemic index Mediterranean-style eating patterns improved some domains of health-related quality of life but not sleep in adults at risk for type 2 diabetes: The MEDGICarb randomized controlled trial. The Journal of Nutrition, 2024, DOI: 10.1016/j.tjnut.2024.07.005, https://www.sciencedirect.com/science/article/pii/S0022316624003857