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Inflammation: medicine’s next big false trail?

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Blaming inflammation for everything from heart disease to aging could be medicine’s next big blunder—just ask the Tsimane of Bolivia.

Medicine has a nasty habit of accusing the wrong guy. For years, it was convinced that ‘bad’ LDL cholesterol was responsible for cardiovascular disease and especially atherosclerosis, when arteries become blocked and stiffen from a plaque buildup, but it currently recognizes LDL as a healing agent trying to fix artery damage. Now it could be about to make the same mistake with inflammation.

Inflammation is the new bad kid on the block. It’s this, and not cholesterol, that’s responsible for heart disease and atherosclerosis, the new theory suggests. It’s also responsible for Alzheimer’s and dementia, and has a hand in psoriasis, rheumatoid arthritis and even the whole aging process, which has been given the catchy name of “inflammaging.”

But how did the body’s own healing response get such a bad rap? Inflammation heals injuries and protects the body from invading viruses, but the inflammaging theory says it becomes a destructive force when it is persistent
and chronic. 

Chronic inflammation is the immune system on constant mop-up duty as it tries to eliminate old and dying cells, scientists believe, but it could also be the result of obesity or a leaky gut that deteriorates with age.1

OK, it wasn’t cholesterol

Heart disease has more to do with inflammation than LDL cholesterol, according to the latest theories on heart health. “The established and earlier concept that passive deposition of lipids into arterial walls with subsequent covering of the deposits by smooth muscle and endothelial cells causes atherosclerosis has changed over the course of time,” said cardiologist Mohammad Tarek Kabbany at Medstar Washington Medical Center. 2

Chronic inflammation is also a factor in rheumatoid arthritis, systemic lupus erythematosus (SLE), psoriasis and HIV infection. And the problems interweave: rheumatoid arthritis patients are 68 percent more likely to suffer a first heart attack than healthy people, while people with psoriasis have a higher risk of cardiovascular disease.

Inflammation is also at the heart of aging. It can cause tissues and joints to deteriorate, but it could also be an unsuspected driver of dementia. People with inflammation in the brain—or neuroinflammation—are more prone to develop Alzheimer’s disease, and the same could also be the case for other types of dementia, as researchers from Cambridge University have shown. 

They scanned the brains of 31 people with frontotemporal dementia—which is caused by ‘junk’ protein buildup—and discovered that areas of the brain with the greatest accumulation of the proteins also had the highest levels of inflammation. But what came first? Researcher Thomas Cope says: “There may be a vicious circle where cell damage triggers inflammation, which in turn leads to further cell damage.” 3

Error, error

Compelling as the evidence is, catching inflammation at the scene of almost every crime, other researchers are warning that medicine is about to make another colossal error on par with the cholesterol theory.

But in order to dispute the inflammaging theory, they have had to garner their evidence far from the West and its poor diet, stress and sedentary lifestyle. Several research groups have spent the past 20 years or so studying the Tsimane people of the Bolivian Amazon—and their findings turn the whole inflammation theory on its head. 

The Tsimane have the lowest rates of heart disease ever recorded by modern medicine—and yet they suffer from chronic inflammation, the very type that is supposed to cause heart disease. They also don’t seem to suffer from obesity or type 2 diabetes, two other problems that have been linked to chronic inflammation. 

Their brains also don’t show the same levels of degeneration as people of similar age in the West, even though inflammation is supposed to attack brain tissue. The fact that their brains don’t atrophy also suggests the Tsimane don’t suffer from dementia or Alzheimer’s.

It’s an “inflammation paradox,” say researchers at the German Sports University in Cologne—but the paradox goes away if the inflammation theory is discounted. 4

Perhaps it’s because the Tsimane’s inflammation is somehow different from that in the West, which is linked to obesity and metabolic disorders. For the Tsimane, inflammation is triggered by respiratory, gastrointestinal and parasitic infections, explained Hillard Kaplan from the University of New Mexico, whose own research confirmed the inflammation paradox.5

His research team had assessed the heart health of 705 Tsimane by using a CAC (coronary artery calcium) test, a conventional method to predict heart problems. Around 85 percent of the Tsimane had zero calcium in their arteries, 13 percent had CAC scores of between one and 100, and just 20 had CAC scores above 100. Among Tsimane who were 75 years old and older, 65 percent had a CAC score of zero, and only four had a CAC score of more than 100. The results were five times lower than typical scores among Western populations of similar age.

Other researchers discovered that chronic inflammation wasn’t harming the brains of the Tsimane, either. The researchers, from the University of Southern California’s Leonard Davis School of Gerontology, scanned the brains of 746 Tsimane between 40 and 94 years old. Compared to similar tests in the West, the Tsimane experienced “a significantly slower decrease in brain volume” than their Western counterparts.6 

“The Tsimane have provided us with an amazing experiment on the potentially detrimental effects of modern lifestyles on our health,” said study author Andrei Irimia.

More than inflammation

More than inflammation

But there’s something more going on. The Hadza hunter-gatherers of Tanzania and the Shuar hunter-horticulturists of Ecuador also have low levels of heart disease—along with low levels of inflammation, which suggests inflammation could be a red herring.

Jens Freese at Cologne’s German Sports University thinks so. Other factors need to be in play for chronic inflammation to begin its damaging journey through the body, he conjectures. The Tsimane’s inflammation is primarily the result of intestinal worms, which would keep the immune system on a higher alert level. The Tsimane also suffer from viral infections that they often catch when they’re hunting, which also triggers an inflammatory response.

Perhaps we could all live with inflammation if we had a lifestyle more like the Tsimane, with healthier diets, more exercise, greater periods of fasting and living without chronic stress. Freese and his team got a glimpse of what this could look like when they carried out two field experiments with small groups of participants in 2013 and 2014.

In both experiments, which are known as the Eifel studies after the national park in Germany where they were carried out, the 20 participants lived a Paleo-like life for four days. They converted to a high fat, low carb diet, they walked up to 16 kilometers (nearly 10 miles) every day, they fasted for up to 14 hours between meals, and when they did eat, they consumed an average of just 1,600 calories a day.

These lifestyle changes are known to be anti-inflammatory—and yet Freese was astonished to discover that in just four days the participants’ inflammatory markers had risen by as much as 170 percent.7

Freese has several theories to explain the phenomenon; one is that the participants were exposed to natural antibiotics released by plants to protect themselves against bacteria and insects, and this triggered the participants’ inflammatory responses. Similar effects have been seen in people who spend a day ‘forest bathing’—essentially a hike through a forest. Their levels of natural killer (NK) cells rise dramatically and stay high for up to 30 days.8 

Another possibility is that the participants changed from their usual near-sterile environments to a natural one, and this may have sparked the immune system into action. It’s also possible the inflammation was the result of physical stress caused by the participants’ high workload combined with a low-calorie diet.  

Similar results were seen in another experiment, this time taking a group on a 10-day hike through the Pyrenees. Again, increases in inflammatory markers were recorded afterwards.9

What can’t be known is if these back-to-nature experiments had any long-term benefits on heart health, diabetes, obesity or dementia protection, as has been seen with the Tsimane.

But there’s the danger that medicine—always looking for the next money-spinning silver bullet—will develop a new generation of anti-inflammatories just as they did when they developed statins to lower cholesterol levels.

Just as cholesterol is trying to repair damaged arteries, so inflammation is responding to a threat. In other words, it’s a reaction, not a cause—but where’s the money in that?

 
 

References

1 

J Gerontol A Biol Sci Med Sci, 2014; 69 Suppl 1: S4-9

2 

American College of Cardiology, “Cardiovascular Diseases in Chronic Inflammatory Disorders,” Jul 18, 2016. www.acc.org 

3 

Brain, 2020; 143: 1010–26

4 

F1000Research, 2018; 7: 252

5 

Lancet, 2017; 389: 1730–9

6 

J Gerontol A Biol Sci Med Sci, 2021; glab138

7 

J Evol Health, 2016; 1: 12

8 

Environ Health Prev Med, 2010; 15: 18–26

9 

Biomed Res Int, 2016; 2016: 6935123

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Article Topics: Atherosclerosis, inflammation
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