What Does Exercise Really Do That an ‘Exercise Pill’ Doesn’t?

After Popeye the Sailor Man eats a can of spinach, he can grow strong muscles. Can the rest of us now also take a pill that does the job of exercise?

In the June issue of the journal Nature, a discovery caught people’s attention. It has made many people who do not like exercising or cannot exercise daydream about the possibilities.

Researchers from Stanford University, Baylor College of Medicine, and their collaborating institutions found a molecule in the blood of lab rats that had undergone vigorous exercise. The substance, Lac-Phe, is an amino acid produced during exercise and is synthesized intracellularly from lactic acid (a byproduct of intense exercise that causes soreness and burning in muscles) and phenylalanine (an amino acid obtained from the breakdown of proteins).

Researchers also discovered that Lac-Phe levels in the blood of athletes are substantially elevated after athletic activity, as well as in horses after competing in races. The data from humans show that the most significant increase of Lac-Phe takes place in sprinting, followed by resistance training, and then endurance training.

Researchers fed Lac-Phe to rats, which were obese due to high fat diet. As it turned out, this substance quickly suppressed the appetite of these rats, and their food intake was reduced by 50 percent in 12 hours, but their exercise amount and energy expenditure did not change.

After 10 days of ingestion of this substance, the rats’ total food intake decreased, their body fat decreased and their body weight also decreased, while their glucose tolerance improved.

This suggests that simply by ingesting Lac-Phe, the rats gained similar effects to those brought about by exercise.

In contrast, when rats were prevented from synthesizing Lac-Phe in a specific way, their food intake after exercise increased and obesity worsened.

Researchers stated that this finding might be more helpful to the elderly or frail people who can’t get enough exercise. Maybe in the future, those suffering from osteoporosis, heart diseases, or other diseases, may fight their illnesses by taking this substance. Stanford University is currently applying for a patent on this substance, which includes its use to treat metabolic diseases.

In fact, this is not the first time that the scientific community discovers a “magic pill” that can bring about the effects of exercise.

In as early as 2008, researchers at the Salk Institute for Biological Studies discovered a substance known as “GW1516”, which can enhance endurance, even the endurance of non-exercisers. As a result, some people call it “exercise in a pill.”

Another study published in Nature in 2020 presented a protein called Sestrin. It is also produced through exercise. Animal studies have shown that this substance can improve endurance and metabolism.

By Taking a Pill, We No Longer Need to Exercise?

After seeing these new studies, many people wonder why we don’t turn these substances into pills. Taking them is equivalent to exercising, and they can also help us lose weight. How convenient!

However, can these magic pills really replace the effects of exercise?

Modern medicine has discovered that when exercising, the human body changes in various aspects, rather than bringing about one or two molecular changes.

The effects of exercise are extremely complex, involving the integrated linkages among and activation of countless molecules, cells, and organs throughout the body. In other words, the human body is like a micro-world; and during exercise, all parts of this world are changing.

Exercise Affects Over 700 Metabolites and Brings Whole-body Benefits

All types of exercise change the metabolism of the entire body.

With the development of assay technologies, more and more metabolites have been discovered to be released through exercise.

Scientists have analyzed blood metabolites before and after intense exercise and found that exercise affects 728 metabolites in the body. After endurance and resistance exercises, 196 metabolites were drastically altered.

During exercise, a variety of tissues, including bones, muscles, adipose tissues, and viscera release various exercise factors into the bloodstream. These factors continue to act on the body, giving us a rich array of benefits.

Six well-recognized, representative metabolites are closely associated with exercise, including alpha-ketoglutarate (AKG), lactic acid, and kynurenic acid (KYNA).

These substances are produced during exercise and flow through the plasma to various tissues and organs in the body, to further exert their associative effects. At the same time, they are also the raw material for many bioactive substances, which are beneficial to the body.

As a result, our appetite decreases; body fat decreases; muscles are strengthened; bone loss is inhibited; insulin resistance, blood pressure, and vascular aging are improved; inflammation is reduced; nerves, kidneys, and many other organs are protected; and neurodegenerative diseases and aging are delayed.

As we age, levels of many metabolites increase in our plasma, some of which may be associated with aging and age-related diseases. Exercise reduces the levels of these substances, and from this perspective, exercise can combat aging.

Gut Bacteria Also Change During Exercise

Besides metabolites, the intestinal microbiome also changes during exercise.

There are significant differences in intestinal microbiome between people who exercise and those who don’t. The intestinal microbiome of athletes is more diverse than average. As the intensity of exercise increases, the abundance of probiotic bacteria like Faecalibacterium prausnitzii, Lachnospira, and Akkermansia muciniphila in the human intestines gradually increases. The more inactive people are, the less probiotic bacteria is found in their intestines.

Butyrate, a short-chain fatty acid, is considered beneficial for intestinal health, as it is the main source of energy for intestinal cells and plays a key role in maintaining the stability of epithelial tissues and maintaining immunity. Butyrate-producing bacteria are more abundant in the intestines of people who exercise, and higher concentrations of butyrate are found in the bodies of people who exercise.

Anti-cancer Mechanisms in the Body Are Continuously Improved During Exercise

When exercising, various anti-cancer mechanisms in the body are constantly being adjusted and improved. In cancer patients, exercise can inhibit the growth and metastasis of cancer cells and improve the treatment side effects.

The right side of the circle in the image shows the anti-cancer mechanisms activated by exercise, including inhibiting cancer cell proliferation and inducing apoptosis (cell death), regulating cancer metabolism, and regulating the immune environment.

The left side shows the positive effects of exercise on cancer, including reducing adverse reactions to cancer treatment, improving the curative effects of cancer treatment, and reducing the risk of cancers.

For instance, physical exercise can significantly relieve fatigue during cancer chemotherapy and also prevent chemotherapy-induced lymphedema, thereby balancing the damage caused by neurotoxic agents. The combination of exercise and radiation therapy can improve apoptosis of cancer cells, which also improves the effectiveness of radiation therapy.

The Brain Also Changes Quietly During Exercise

Exercise affects different parts of the brain.

Older adults with high aerobic capacity have relatively large hippocampal volumes. Performing moderate-intensity aerobic exercise three times a week for 12 consecutive months can increase the volume of the hippocampus by approximately 2 percent. Exercise also counteracts the atrophy of the prefrontal cortex and anterior cingulate cortex.

In depressed patients, the brain becomes impaired, with volumetric reductions in the hippocampus, anterior cingulate cortex, and prefrontal cortex, as well as compromised white matter integrity. Exercise can counteract these changes and further combat depression.

How Do the Elderly and Those with Motor Difficulties Exercise?

As noted by the researchers who discovered the effects of Lac-Phe, the elderly can have a hard time exercising. What should they do?

Generally speaking, on a weekly basis, adults should carry out at least 150 minutes of moderate intensity activity, such as brisk walking; and two days of muscle training, such as deep squats.

For seniors aged 65 and older, it is also recommended to add exercises to improve their balance, such as practicing standing on one foot.

Seniors who are not physically strong can do it gradually.

They should start with the simplest exercises such as stretching and walking, and gradually increase the duration and intensity of exercise, if their body is not too tired, eventually reaching the ideal amount of exercise.

People with specific diseases and mobility problems, such as past knee surgery and pulmonary obstruction, can consult a rehabilitation physician or physical therapist. They should find the right type of exercise for themselves, ideally one that can help rehabilitate their body as they exercise.

In addition to simple walking, water aerobics, and yoga, there is also a form of exercise increasing in popularity that is suitable for the elderly and people with limited mobility, which is qigong. Qigong movements are usually slow and soft, and they can also play a role in regulating physical and mental health.