Medicine

Candy Crush: Could Blue M&M’s Repair Spinal Cord Injuries? | by Tara Fernandez | Oct, 2021

The same chemical in the food dye keeps damaged nerves alive

Photo by Ivan J. Long from Pexels

They melt in your mouth, not in your hands. But could M&M’s — in particular the blue ones — hold the key to healing the irreversible damage caused by spinal cord injuries?

One of the Ms in their name comes from Forrest Mars, Sr, who, as legend has it, first observed soldiers snacking on chocolate nibbles encased in a hard, sugar coating in the 1930s. This was Mars’ inspiration for the candy’s iconic color and shape. By the 1940s, people all over the U.S. were enjoying the chocolates. In 1941, the sweets were branded with the signature letter M. Since 2003, M&M’s have been sold in over 100 countries.

The candies are made through a multi-step process that begins with milk chocolate being injected into mold cavities. Vegetable oil, cocoa butter, sugar and other ingredients are then added to the individual cavities, which are then filled with a flavored candy mixture consisting of corn syrup, hydrogenated coconut oil, sugar, and colors.

The colors you’ll find in today’s M&M packs are the people’s choice. In 1995, M&M Mars asked consumers to vote on the colors they wanted to be included in their candy. Blue was chosen number one, with green in second place, followed by red, brown, and yellow.

What gives candy fan’s top choice their signature hue? Blue M&M’s are colored using a mixture of two FDA-approved food dyes, Blue №1 and Blue №2.

Blue №1, or Brilliant Blue FCF, is a synthetic dye manufactured by the Japanese chemical company Kawaken Fine Chemicals. First synthesized in 1935, it is currently approved for use in food. The FDA considers Blue №1 generally safe for general consumption; the only listed side effects are migraines and difficulty sleeping. Once consumed, the dye passes through the system, with 95% being excreted.

The other blue, also known as indigotine, is a plant-based dye that is the same chemical used in denim. Its origins are indigo, a chemical extracted from the indigo plant (Indigofera), which is native to South Asia. It was once used for clothing because it doesn’t fade, but synthetic indigotine dyes have long replaced the plant-based versions.

Modern manufacturers have access to various shades of blue indigo because they can be mixed — the result is a remarkably profound color.

According to M&M Mars, Blue №1 is more stable than Blue №2, which means it sticks around longer before changing color — a quality they say makes it ideal for their candy coating process. In addition to its blue hue, the synthetic dye also imparts a more vibrant shade of blue than indigotine.

One of the M&M blues, in particular, has shone in applications outside the food industry. For the chemistry nerds in the room, Brilliant Blue is made through a chemical reaction involving the condensation of 2-formylbenzenesulfonic acid and the appropriate aniline followed by oxidation.

It’s Brilliant Blue’s biological effects that have caught the eye of biomedical researchers. These compounds inhibit the activity of purinergic receptors, a family of proteins that are related to neurotransmitters. In the brain, purinergic receptors are involved in memory formation and learning. When activated, they also increase heart rate and blood pressure, a side effect that some medications have exploited. The receptors are also involved in inflammation.

With their role in cell communication, cancer scientists hypothesized that by inhibiting purinergic receptors, Brilliant Blue may stop tumors in their tracks.

In 2013, scientists from the University of California-San Diego reported that injections of Brilliant Blue FCF into rats caused their bladder tumors to shrink. It works by disrupting communication between malignant cells and nerves that respond to pain when stimulated — the researchers believe it does so by altering cell membranes.

In spinal cord injury, communication between the brain and nerves below the injury site is cut off, causing paralysis. Neuroscientists have explored many avenues for repairing these communication lines, including injecting stem cells into the injury site. However, the results have been underwhelming: stem cell recipients are still unable to walk out of treatment centers.

In search of other therapeutic strategies, a group of scientists led by Danish neuroscientist Maiken Nedergaard began screening chemical compounds that could reduce inflammation after spinal cord injuries in mice.

Nedergaard found that the spinal cord abundantly expresses a molecule called P2X7, known in the field as “the death receptor”. When stimulated, P2X7 triggers apoptosis — the suicide of cells — by allowing ATP molecules to stick onto motor neurons, activating the self-destruct button.

Therefore, chemicals that could block the ATP receptors could be prime drug candidates for spinal cord injury.

One molecule, called OxATP, showed promise by blocking an ATP receptor in neurons. The problem, however, was that OxATP was incredibly toxic and could only work if it was injected directly into the spinal cord.

After a few other candidates failed to show results, Nedergaard and her team turned to Brilliant Blue FCF, a chemical similar to OxATP. In their mouse model, they tested a derivative dye called Brilliant Blue G, or BBG, with impressive results.

The rats that received the treatment could walk again, albeit with a limp, after their injuries. However, the control (untreated) animals remained immobile.

“Administration of BBG 15 min after injury reduced spinal cord anatomic damage and improved motor recovery without evident toxicity,” wrote the authors.

Most promisingly, the dye can cross the blood-brain barrier so that it can target damaged neurons. All of these features make BBG a good candidate for restoring neural communication in patients.

Will BBG help spinal cord injury patients rise? For now, research into the field continues. This has also spilled over to the treatment of other neurological conditions such as Alzheimer’s disease.

A recent study proposes that BBG could help treat Alzheimer’s by inhibiting the buildup of amyloid-β proteins. In Alzheimer’s, amyloid-β proteins gather and grow into plaques on the surface of human neurons, eventually killing them. Researchers in these studies were able to show that BBG could prevent cell death in neurons grown in the lab, and showed promising results in animal models.

“We conclude that BBG prevents the learning and memory impairment and cognitive deficits induced by the toxicity of soluble Aβ, and improves the development of dendritic spines in hippocampal neurons in an AD model mouse,” say the authors.

So, while eating more blue M&M’s is unlikely to keep your neural networks running smoothly, the hope is that the therapeutic application of BBG will soon be available to help patients with neurological conditions.


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