Medical Bulletin 10/ June/ 2024

According to a study published in the journal JAMA Ophthalmology, melatonin supplementation is linked to a reduced risk of developing age-related macular degeneration (AMD) and slowing its progression, suggesting potential as a preventive therapy.

Age-related eye disease, also called macular degeneration, is a leading cause of vision loss among older adults. It primarily affects the macula, the central part of the retina responsible for sharp, central vision needed for tasks like reading and driving.

Melatonin, a hormone produced by the pineal gland, is well-known for regulating sleep-wake cycles, but recent research suggests it may also help reduce the risk of age-related eye diseases, including age-related macular degeneration (AMD). Melatonin possesses potent antioxidant properties, which can protect retinal cells from oxidative stress—a major contributing factor to AMD. By neutralising free radicals, melatonin helps to prevent cellular damage within the retina.

In the study, researchers analyzed data from the TriNetX database from December 2023 to March 2024. The retrospective study included patients aged 50 and older, divided into groups based on their history of age-related macular degeneration (AMD) and melatonin use. Propensity score matching was employed to compare melatonin users and non-users regarding the risk of developing any form of AMD or the progression from nonexudative to exudative AMD.

The result showed that:

1. Use of melatonin was associated with a 58% reduction in the risk for developing AMD, according to the researchers.

2. In people with nonexudative AMD, use of the supplement was linked to a 56% lower risk for progression to exudative AMD.

3. The findings were consistent across age groups, suggesting melatonin's benefits may extend to older populations at higher risk for AMD.

The findings suggested that melatonin use was associated with a decreased risk of development and progression of AMD. Although lifestyle factors may have influenced this association, these findings provide a rationale for further research on the efficacy of using melatonin as a preventive therapy against AMD.

Reference: Jeong H, Shaia JK, Markle JC, Talcott KE, Singh RP. Melatonin and Risk of Age-Related Macular Degeneration. JAMA Ophthalmol. Published online June 06, 2024. doi:10.1001/jamaophthalmol.2024.1822

According to a study published in the journal The Lancet Diabetes and Endocrinology, Vitamin D supplementation does not reduce falls or fracture risk and also does not improve bone mineral density.

As people age, bone mineral density (BMD) tends to decrease, leading to a higher risk of fractures. This decline in BMD is primarily due to changes in bone remodeling, where the balance between bone resorption (breakdown) and bone formation shifts, resulting in a net loss of bone mass.

This weakened bone structure makes adults more susceptible to fractures, particularly in weight-bearing bones like the hips and spine, increasing the risk of osteoporosis and related complications.

Vitamin D is a fat-soluble vitamin essential for health and plays a role in immune function and reducing inflammation. The primary sources of vitamin D are sunlight exposure, certain foods like fatty fish and fortified dairy products, and dietary supplements.

The study, carried out by researchers from the Universities of Auckland and Aberdeen, was a meta-analysis of 81 clinical trials, including over 53,000 patients, looking at the effects of vitamin D on fracture rates, falls and bone mineral density. Most studies included women aged over 65 with serum vitamin D levels of less than 50nmol/L and taking vitamin D doses of more than 800IU per day.

The analysis found that vitamin D supplementation did not reduce total fractures, hip fractures or falls by 15% – a clinically meaningful threshold. When the researchers reduced the thresholds, they found that vitamin D still did not reduce falls by 7.5% or total fractures by 5%. They also found that bone mineral density did not increase by a clinically significant level in those taking vitamin D.

‘In summary, vitamin D supplementation did not have meaningful effects on fracture, falls, or bone mineral density, and future trials are unlikely to alter these conclusions. Therefore, there is little justification for the use of vitamin D supplements to maintain or improve musculoskeletal health, and clinical guidelines should reflect these findings,” said the authors.

Reference: Mark J Bolland, PhD, Andrew Grey, MD, Alison Avenell, MD; Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis; The Lancet Diabetes and Endocrinology; DOI:https://doi.org/10.1016/S2213-8587(18)30265-1

In a study published in the journal Nature, researchers have identified a significant cause of inflammatory bowel disease (IBD) and several other immune disorders affecting the spine, liver, and arteries, offering new hope for millions of people worldwide.

Nearly 5% of humans live with an autoimmune or inflammatory disease. They arise when the immune system attacks the bowel, causing an array of debilitating symptoms from abdominal pain and weight loss to diarrhoea and blood in stools. While medicines such as steroids can ease the symptoms, some patients require surgery to remove part of their bowel.

These heterogeneous conditions, ranging from Crohn’s disease and ulcerative colitis to psoriasis and lupus, all require better therapies, but only 10% of drugs entering clinical development ever become approved treatments. This high failure rate is mainly due to a lack of efficacy and reflects the poor understanding of disease mechanisms.

In the study, Dr. James Lee and his team made a key discovery while researching a "gene desert," a part of DNA on chromosome 21 that doesn't code for proteins but is linked to IBD and other autoimmune diseases. They found a section of DNA that acts like a volume control for nearby genes. This "enhancer" was only found in immune cells called macrophages and increased the activity of a gene ETS2, raising the risk of IBD. The researchers showed that ETS2 is important for the inflammatory behaviour of macrophages and their ability to damage the bowel in IBD. This same process is believed to cause other autoimmune disorders and some rare diseases affecting the liver and arteries.

“Crohn’s and colitis are complex, lifelong conditions for which there is no cure, but research like this is helping us to answer some of the big questions about what causes them. What we have found is one of the very central pathways that goes wrong when people get inflammatory bowel disease and this has been something of a holy grail. This research is a really exciting step towards the possibility of a world free from Crohn’s and colitis,” said Lee.

Reference: Stankey, C.T., Bourges, C., Haag, L.M. et al. A disease-associated gene desert directs macrophage inflammation through ETS2. Nature (2024). https://doi.org/10.1038/s41586-024-07501-1