The Perils of Inflammation

Health!  Wealth!  Happiness!  I’m Dr. Michael Greger and you’re listening to the Nutrition Facts podcast.  And while I can’t promise you all of those things, if you take a listen to the evidence-based nutrition found in this podcast, chances are you’ll learn something that you can use to make a positive change in your diet and in your health.  My job here is to bring you the information you need to make that reality possible.

Today, we look at inflammation.  It turns out that inflammation may play a role in a variety of disease states–premature aging, periodontal disease, obesity, skin aging, diabetes, multiple sclerosis, cancer, and inflammatory bowel disease, of course, and that’s just for starters.  

In our first story, we look at the results of an elegant experiment where spices—such as cloves, ginger, rosemary, and turmeric—are tested for their anti-inflammatory capacity.

Once in a while, I come across a study that’s so juicy, I do an entire video about it. It’s like my “Which Fruit Fights Cancer Better?” video, or the “Best Cooking Method” one, or that one comparing thousands of foods. Well, this is one such study.

A group of researchers at U of F Gainesville and Penn State set up an elegant experiment. We’ve known, ounce per ounce, that herbs and spices have some of the greatest antioxidant activities known—but, that’s in a test tube. Before we can ask if an herb or spice has health benefits, it’s first necessary to determine whether it’s bioavailable. This has never been done, until now.

They could have [went] the easy route, and just measured the change in antioxidant level in one’s bloodstream before and after consumption. But, the assumption that the appearance of antioxidant activity in the blood is an indicator of bioavailability has a weakness. Maybe more gets absorbed than we think, but doesn’t show up on antioxidant tests, because it gets bound up to proteins or cells. So, they attempted to measure physiological changes in the blood. They were interested in “whether absorbed compounds would be able to protect [white blood cells] from an oxidative or inflammatory injury”—whether it would protect the strands of our DNA from breaking when confronted by free radicals. They also wondered if the consumption of herbs and spices “might alter…cellular inflammatory response[s] in the presence of a physiologically relevant inflammatory insult.” What does this all mean?

Well, what they did was take a bunch of people and had each of them eat different types of spices for a week. There are so many really unique things about this study, but one was that the quantity that study subjects consumed was based on the usual levels of consumption in actual food. Like, the oregano group was given a half-teaspoon a day—the kinds of practical quantities people might actually eat once in a while. Then, at the end of the week, they drew blood from the dozen or so people they had adding black pepper to their diets that week, and compared the effects of their blood to the effects of the blood of the dozen on cayenne, or cinnamon, or cloves, or cumin. They had about ten different groups of people eating about ten different spices.

Then, they dripped their plasma (the liquid fraction of their blood) onto human white blood cells in a Petri dish that had been exposed to an inflammatory insult. They wanted to pick something really inflammatory, so they chose oxidized cholesterol, which is like what you’d get in your bloodstream after eating something like fried chicken. So, they jabbed the white blood cells with oxidized cholesterol, and then measured how much TNF they produced in response.

Tumor necrosis factor is a powerful inflammatory cytokine, infamous for the role it plays in autoimmune attacks, like inflammatory bowel disease. Compared to the blood of those who ate no spices for a week, was the blood of those eating black pepper able to significantly dampen the inflammatory response? No. Cloves, ginger, rosemary, and turmeric were able to significantly stifle the inflammatory response. And, remember, they weren’t dripping the spices themselves on these human white blood cells, but the blood of those who ate the spices. So, it represents what might happen when cells in our body are exposed to the levels of spices that circulate in our bloodstream after normal daily consumption. Not megadoses in some pill—just the amount that makes our spaghetti sauce taste good, or our pumpkin pie, or curry sauce.

There are drugs that can do the same thing. Tumor necrosis factors are such “major mediators of inflammation and inflammation-related diseases” that there are these TNF-blocking drugs on the market for the treatment of inflammatory diseases—like osteoarthritis, inflammatory bowel disease, psoriasis, ankylosing spondylitis—which rake in, collectively, more than $20 billion a year, because drug companies charge people $15,000 to $20,000 a year for the drug. At that price, the side effects better be hugs and rainbows. But, no, these drugs carry a black label warning because they can cause things like cancer, heart failure. If only there were a cheaper, safer solution.

Curcumin, the yellow pigment in turmeric, in a spice that’s a tad cheaper, and safer. But, does it work outside of a test tube? There’s evidence that it may help in all the diseases for which TNF blockers are currently being used. And so, with health care costs and safety being such major issues, this golden spice, turmeric, may help provide the solution.

There is a food that offers the best of both worlds—significantly improving our ability to detox carcinogens, like diesel fumes, and decreasing inflammation in our airways, all the while improving our respiratory defenses against infections.  Here’s the research.

Outdoor air pollution may be the ninth leading cause of death and disability in the world, responsible for millions of deaths from lung cancer, emphysema, heart disease, stroke, and respiratory infection. In the U.S., living in a polluted city was associated with a 16, 27, and 28% increase in total, cardiovascular, and lung cancer death, compared to living in a city with cleaner air. Living in a city with polluted air may lead [to] up to a 75% increase in the risk of a heart attack. No one wants to be living in a traffic jam, but it’s better than dying in a traffic jam.

“In addition to causing deaths, air pollution is also the cause of a number of…health problems.” It may not only exacerbate asthma, but increase the risk of developing asthma in the first place. These pollutants may trigger liver disease, even increase the “risk of diabetes.” “[E]ven when atmospheric pollutants are within legally established limits, they can be harmful to health.” So, what can we do about it?

Paper after paper describing all the terrible things air pollution can do to us, but most failed to mention public policy. We’re making “great strides in demonstrating the harmful effects, [but] public authorities are not using these data to” reduce emissions, as they might inconvenience the population, “and, therefore, might not be politically acceptable.”

To treat the cause, we need better “vehicle inspections, efficient public transport,…bus lanes, bicycle lane[s], [even] urban tolls”—to help clean up the air. While we’re waiting for all that, is there anything we can do to protect ourselves?

Well, our body naturally has detoxifying enzymes, not only in our liver, but lining our airways. Studies showing that people born with less effective detox enzymes have an exaggerated allergic response to diesel exhaust, suggesting that these enzymes actively combat the inflammation caused by pollutants in the air. A significant part of the population has these substandard forms of the enzyme, but either way, what can we do to boost the activity of whichever detoxification enzymes we do have?

Well, if you remember, broccoli can dramatically boost the activity of the detox enzymes in our liver. But, what about our lungs? Researchers fed some smokers a large stalk of broccoli every day for ten days to see if it would affect the level of inflammation within their bodies. Why smokers? Because smoking is so inflammatory that you can end up with elevated C-reactive protein levels for “up to 30 years…after quitting,” and that inflammation can start almost immediately after we start smoking. So, it’s critical to never start in the first place.

But, if you do, you can cut your level of that inflammation biomarker CRP nearly in half, after just ten days eating a lot of broccoli. Appears to cut inflammation in nonsmokers as well—maybe explaining, in part, why eating more than two cups of broccoli, cabbage, cauliflower, kale, or other cruciferous veggies a day is associated with 20% reduced risk of dying, compared to eating a third a cup a day, or less.

So, what about air pollution? We know the cruciferous compound is “the most potent known inducer” of our detox enzymes; and so, most of the research has been its ability to fight cancer. They tried to see if it could combat “the proinflammatory impact of…pollutants such as diesel exhaust.” We don’t inhale broccoli; we don’t snort it; we eat it. Can it still get into our lungs and help? Yes, two days of broccoli-sprout consumption, then you suck some cells out of their nose, and up to 100 times more detox enzyme expression, compared to eating a non-cruciferous vegetable (alfalfa sprouts). Now, all we have to do is squirt some diesel exhaust up their nose, which is what some UCLA researchers did—an amount equal to daily rush-hour exposure on the Los Angeles freeway. Within six hours, the number of inflammatory cells in their nose shot up, and continued to rise. But, in the group that had been getting a “broccoli sprout extract,” the inflammation went down, and stayed down. 

Since the dose in these studies is equivalent to the consumption of one or two cups of broccoli, their “study demonstrates the potential preventative and therapeutic potential of broccoli.”

But, if broccoli is so powerful at suppressing this inflammatory immune response, might it interfere with normal immune function? After all, the battle with viruses, like influenza, can happen in the nose. Let’s drip some flu viruses into the nostrils of broccoli-sprout eaters, and find out. And, what you get is the best of both worlds—less inflammation, yet an improved immune response. After eating a package of broccoli sprouts every day, our body is able to keep the virus in check, potentially offering “a safe, low-cost strategy for reducing influenza risk” among high-risk populations. So, better immune function, yet less inflammation, potentially “reducing the impact of…pollution on allergic disease and asthma”—at least for “an enthusiastic broccoli consumer.”

But, what about cancer, detoxifying air pollutants throughout the rest of our body? We didn’t know, until now. Off to China, where they have some of the worst air pollution in the world. And, by day one, those getting the broccoli sprouts were able to get rid of 60% more benzene from their bodies, a “rapid…highly durable elevation [in] the detoxification of…a known human carcinogen.” Now, this was using broccoli sprouts, which are highly concentrated—equivalent to about five cups of broccoli a day. So, we don’t know how well more modest doses would work. But, if they do, eating broccoli could provide “a frugal means to attenuate [the] long-term health risks” of air pollution.

If depression can be induced with pro-inflammatory drugs, might an anti-inflammatory diet be effective in preventing and treating mood disorders?  Here’s your answer.

Depression affects more than 150 million people worldwide, making it a leading cause of losing healthy years of life as a result of disability. In fact, by 2020, depression may be the second leading cause of healthy years of life lost, second only to heart disease. Why is depression so common? Well, it is said, “Nothing in biology makes sense except in the light of evolution.” But, why would we evolve to get depressed?

Depression poses a baffling evolutionary puzzle if it has such negative effects, but yet it remains so common and heritable, meaning a big chunk of risk is passed through our genes. So, there must be some kind of adaptive benefit. Otherwise, presumably, it would have been naturally selected against. Maybe, depression is an evolutionary strategy for defense against infection.

Infection has been the leading cause of mortality throughout human history. The average life expectancy was 25, and it was not uncommon for half our kids to die. With such stark capabilities, infection has been a critical and potent driving force in natural selection.

When we become infected, there is a surge of inflammation as our body mounts a counterattack, and then what happens? We feel lousy. We feel sick.  We get weak, tired, slow, and sleepy. We don’t want to see anyone; we don’t want to do anything; all we want to do is sleep. It’s like we’re depressed—and that’s great for fighting infection. Not only does it help us conserve energy so we can put up a good fight, but reduces social contact. We’re not running around infecting everyone.

It’s the same reason we evolved to think poop doesn’t smell good, or decaying flesh. That keeps us safe from infection. In fact, we see this phenomenon with other social animals, like honeybees and mole rats, who feel impelled to crawl off and die alone when they get sick, which reduces the risk for the rest of the community.

The relationship between mental health and inflammation was first noted in 1887, for which the only psychiatrist to ever win the award got a Nobel Prize. But what evidence have we accumulated in the century since that inflammation causes depression? Well, people who are depressed have raised inflammatory markers, such as C-reactive protein.  Inflammatory illnesses are associated with greater rates of major depression. Indeed, that’s what’s found in a variety of inflammatory conditions including more kind of benign inflammatory conditions, like asthma and allergies. And, you know, that’s important, suggesting the mood symptoms are not simply ‘feeling bad about having a terrible disease,’ but may be directly tied to the inflammation. And, most powerfully, you can actually induce depression by inducing inflammation, like when we give interferon for certain cancers or chronic infections—up to 50% go on to suffer major depression. Even just giving a vaccine can cause enough inflammation to trigger depressive symptoms. Taken together, these studies are strongly suggestive of inflammation being a causative factor of mood symptoms.

So, can an anti-inflammatory diet help prevent depression? We didn’t know, until about 43,000 women without depression were followed, along with their diets, for about a dozen years to see who became depressed, and it was those who ate a more inflammatory diet pattern, characterized by more soda, refined grains and meat, suggesting that chronic inflammation may underlie the association between diet and depression.

Normally, we think of omega-3’s as anti-inflammatory, but they found fish to be proinflammatory, associated with increased C-reactive protein levels consistent with recent findings that omega-3’s don’t seem to help with either depression or inflammation. The most anti-inflammatory diet is plant-based, which can cut C-reactive protein levels by 30% within two weeks, perhaps because of the anti-inflammatory properties of antioxidants.

I’ve talked about this before, but never really explained why antioxidants are anti-inflammatory. See, oxidative damage caused by free radicals may cause an autoimmune response in the body by changing the chemical structure of otherwise ubiquitous molecules to generate new structures that the body attacks as foreign. For example, when LDL cholesterol gets oxidized, our body creates antibodies against it and attacks it. And, so, clinical depression can be accompanied by increased oxidative stress and the autoimmune inflammatory response it creates.  Free radicles lead to autoimmune inflammation. 

Where else does inflammation come from in our diet? Endotoxins, right?  It’s worth reviewing how the endotoxins in animal products can cause a burst of inflammation within hours of consumption. What does that do to our mood? If you inject endotoxin into people, within a few hours, inflammation shoots up, and so do feelings of depression, as well as feelings of social disconnection between people.

Although previous research has demonstrated that inflammatory activity contributes to depressive symptoms, no work in humans has examined the effect of experimentally induced inflammation on anhedonia, the lack of reaction to pleasurable stimuli; this is an important symptom of depression.  No work has been done, that is, until now.  Within hours of endotoxin hitting their bloodstream, these experimental subjects not only started to feel depressed, but they had significant reductions in activity in the reward center of their brain. They were less excited about winning money playing video games, for example, in the study.

But by eliminating animal products, and eating antioxidant-rich diets, we may be able to prevent or treat depression.

To see any graphs, charts, graphics, images or studies mentioned here, please go to the Nutrition Facts podcast landing page.  There you’ll find all the detailed information you need – plus links to all the sources we cite for each of these topics.

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Thanks for listening to Nutrition Facts. I’m Dr. Michael Greger.

This is just an approximation of the audio content, contributed by Allyson Burnett.