A vibrating pill could help treat obesity, pig study finds

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They say that weight loss is a matter of taking in fewer calories and burning as many as possible. A sort of supply and demand issue. But is the demand in one's head or stomach, and can that be controlled? Some diets purport stopping eating a meal when one feels 80% full, to allow for the body to catch up to itself and register a real feeling of fullness. But, many people can't control themselves, and so they continue to eat. It can be called making a pig out of oneself, but pigs might prove to be the solution to weight loss after all! Read on.

Image from Pixabay

Why do we feel full when we eat? Surrounding our stomach is a network of nerves called IGLEs (intraganglionic laminar endings). These are connected to nerve clusters called ganglia which run through two layers of smooth muscle outside of the stomach lining. IGLEs detect mechanical pressure from the stomach and send signals to the muscles to loosen or tighten, in order to allow food in or to squeeze it through to the small intestine. When they detect enough pressure, it suggests to the brain that the stomach is filled with food, and it then tells the body to stop.

IGLE nerve in a cross-section of stomach (adapted from Frontiers in Physiology)

If the goal is to force a person to eat less, then giving them a sensation of a full stomach is needed. Drugs are costly and potentially dangerous. Putting in a balloon was done as early as 1979. In 2017, researchers reviewed studies on the effects of inserting a balloon then filling it with saline (salt water) solution directly into the stomach. Lean people have a stomach volume of 1,000 milliliters (4 cups), and obese people's stomach has a volume of 1,920 milliliters (8 cups). So, various makers of stomach balloons allow for them to be inflated to 200, 400, 600, or 800 mL to take up stomach volume. Most balloons are inserted and filled under anesthesia, which adds another layer of complication and cost.

Stomach balloon insertion and inflation (Mayo Clinic)

The 2017 review found mixed results. Whether patients had diet treatment, and whether the balloon was a certain size both affected the results in a 3-month study.

• balloon only (300 mL): 3.2 kg lost + 4.1 kg
• balloon plus diet: 5.1 kg lost + 4.7 kg
• diet only: 6.9 kg lost + 5.9 kg
• no treatment: 0.6 kg lost + 2.5 kg

Researchers at Harvard University wondered whether stimulating the muscles around the stomach lining could be done and what effect that would have. Electrical stimulation was probably not a feasible technique. As far back as 1966, it was known that vibrations like those used in physical therapy massage, when applied to the body, can cause muscles to contract. So, Professor Shriya Srinivasan and a team of scientists at Harvard University developed a small device called a Vibrating Ingestible BioElectronic Stimulator (VIBES) pill which patients could swallow before eating. As the pill rested against the inside of the stomach, its vibrations might cause the brain to think stomach muscles were reacting to a volume of food in the stomach. The VIBES pill is 31 mm (1.2 inches) long and 9.8 mm (0.38 inches) wide.

VIBES pill inside the stomach of a pig (Science Advances 2023)

It has a motor and battery. The pill is coated with gelatin that holds down a pin; when stomach acid dissolves the gelatin, the pin moves to the on position to start the vibration. The vibrating waves trick the IGLEs nerves to send a false signal of an expanding stomach to the vagus nerve and then to the medulla in the brain. When the brain has the illusion that the stomach is full, it then reduces the amount of a "hunger hormone" sent to the body. 

Faking fullness with the VIBES pill (Science Advances, 2023)

Srinivasan's team confirmed what the VIBES pill did as follows. First, they inflated the pig's stomach with an endoscope to 30%, 60%, and 90% of its maximal volume. When they held those volumes for 3 minutes, they recorded electrical impulses from the vagus nerve. They compared those data with what vibrations at 60 Hz, 80 Hz, and 100 Hz did to the nerve. The results were virtually identical.

Top: results showing vagus nerve signal with endoscopic inflation of stomach

Bottom: results showing vagus nerve signal with vibration (from Science Advances, 2023)

Srinivasan and coworkers tested the pill on a dozen Yorkshire pigs 4-6 months old. After two weeks, and 108 meals, the experimental pigs ate less than those given a placebo. Pigs with VIBES pills ate 58.1% of food provided, while the control pigs ate 78.4% of food given to them, a significant difference.

Three pigs were tested further. They had the VIBES treatment, then none, then back on VIBES. Researchers measured the percentage of the meal that they ate during those times. How much they ate returned to normal right away without the pill (left graph, white area), which suggested eating behavior was dependent on the pill's vibrations. They also measured how much weight four pigs gained with and without the VIBES pill. The graph on the right shows less weight gained with VIBES treatment, matching the smaller amount of food eaten.

Data from Science Advances, 2023)

The concept of the VIBES pill is that people will take it before every meal, as the pigs did, and it will eventually find its way out of the body in the feces. No damage was seen to the stomach lining after Srinivasan's experiments were over, even though the pill is right at the maximum size allowed for humans to swallow it. The data from Harvard University will be used to set up human clinical trials. Pigs were chosen for this experiment because their stomach is similar to a human's, not just because of the stereotype of obese people eating like pigs.