Seven Habits That Can Influence Inflammatory Physiology

All right, so the top voted question was, in your opinion, what are the top 5 ways, diets, supplements that you can do to reduce inflammation? And I think that you can address this question by thinking about things that you can cut out of your diet or your lifestyle or things that you can add. And so I'm going to address both of those in most cases. Probably counter to what a lot of people talk about. People always talk about cutting out, cutting out, cutting out. And I think there's a big problem with not getting the right things. And I think by— there's an association there with when you actually start to get the right things, you naturally cut things out, right? So because there's not room to do everything, right?

But one of the top cutting out things would be the most intuitive and obvious, and you probably all know the answer, and that is cutting out refined sugar. But I'll just highlight that point. The people that are healthy, so not overweight, not sedentary, these are just about 29 healthy, normal healthy young men, were given 20 ounces of a sugar-sweetened beverage to drink, so like a Coke, right, for 3 weeks. And the men experienced 60 to 100% increase in a biomarker of inflammation called C-reactive protein. Many of you have heard of it— CRP. C-reactive protein is probably one of the most standard biomarkers of inflammation that's used. 60% to 100% increase after 3 weeks. That is enormous.

Um, you know, higher than normal C-reactive protein levels are associated with, you know, long-term disease risk, cardiovascular disease risk, cancer risk, Alzheimer's disease risk. It's also known to like play a role in depression. So we're talking about affecting mood and behavior. So there's really, you know, every reason to not take in added sugar when you know, like you know you got to live once in a while, right? But like that's probably the main thing, and it's one of the main things that I try to have family members do, you know, is cut out the refined sugar.

It also, in that study, the healthy young men had a pretty big jump in their small dense LDL particle number, which as we've talked about many times in this Q&A, the small dense LDL particles are really the most atherogenic. So they're the ones that are playing the biggest role in causing atherosclerosis and increasing cardiovascular disease risk in general. So they didn't have to eat any saturated fat to do it either. All they had to do was drink a bunch of soda, right? I mean, so it's something that really makes you think about how terrible drinking sugar-sweetened beverages are, and it's pretty ubiquitous in— I would say in, uh, in the United States at least. The next obvious, uh, to me a pretty obvious lifestyle factor would be adding a relatively robust dose of omega-3 fatty acids.

You know, so the questions about inflammation, you know, chronic low-grade inflammation is— it promotes many of the hallmarks of aging. And it, you know, there's a, there's a term called inflammaging, and inflammaging is, you know, it's, it's, it's, it's not just your immune system being activated because of a pathogen, right? It's just chronic activation of the immune system. Like I said, sugar-sweetened beverages is doing it, and there's other, other things that we're exposed to on a daily basis from our environment that are also leading to chronic inflammation. And so the resolution of that inflammation is really where omega-3 shines.

And so, for example, there's something called specialized pro-resolving mediators, SPM for short, and there's 4 different families of SPMs that have been identified. So there's the resolvins, the lipoxins, the protectins, and the maresins, and these SPMs basically are resolving inflammation through a variety of different mechanisms. It's just unbelievable the effect they can have on lowering the overall inflammatory burden. Even when you want your immune system to be active, when you're exposed to a pathogen, you don't want your immune system to be hyperactive and, you know, that's kind of a problem is that when your body is posed with a threat, your immune system responds but oftentimes the innate immune system, so this is the part of the immune system that's not making antibodies.

It's just firing away a lot of different what are called cytokines, and these cytokines are signaling to other immune cells to come and, you know, engulf and basically get rid of pathogens, whether that's a virus or a bacteria. And so, you know, there's a lot of collateral damage with that. And so this specialized, you know, the specialized pro-resolving mediators, the SPMs, are just so important for resolving that inflammation. And so there was actually a clinical trial that, um, with healthy people where omega-3 fatty acid supplementation for basically 24 hours— after 24 hours of supplementation, um, there was a huge boost in these SPMs in people's blood. And 2, 4, 6, 24 hours later, like, I mean, it was like, it was pretty, pretty robust.

And so what you're, what you're seeing here is that biomarkers of resolving inflammation are, are really, um, they're occurring even just 2 hours after, after taking omega-3, and they're lasting for up to 24 hours. So there's sort of a long tail effect. There's a lot of clinical studies that have shown omega-3 supplementation can lower biomarkers of inflammation, but also can lower biomarkers of disease risk, right? Cardiovascular disease risk being, being a big one. I mean, it's, it's prescribed to people with cardiovascular risk factors like high triglycerides, for example. So I think that's another major point of low-hanging fruit, things that can be easily done to mitigate inflammation.

And it's, you know, there's been studies showing that low omega-3 intake is responsible for you know, almost as many deaths a year as eating trans fats. Actually, it was a little bit more than that. You know, so basically just not getting enough omega-3 is causing a lot of problems. And that's where I was talking about there's the taking away and then there's the adding to your diet. And it's, you know, the taking away, obviously refined sugar is a big one, but the not getting the important stuff is also a big one. So I would say— 2, anywhere 2 to 4 grams of omega-3 seems to be a real good sweet spot. Um, probably I tend to be more on the high end, and sometimes I go from 4 to 6 grams, but I'm obviously not telling you to do that. I'm just telling you that's what I do.

I think we're going to start to have an exponential increase in data coming from omega-3, and people are going to start— it's going to start to really show that that literally taking a pretty quality omega-3 supplement is a low-hanging fruit for basically improving the way we age by keeping inflammation in check. And inflammation is a major— plays a major role in accelerating aging. So I see people in the chat like Colleen asking about what about omega-6 overload? And this is a question that is often asked is, you know, what about the omega-3 to omega-6 ratio?

And, you know, you see a lot of people, especially in like the anti-plant communities, focusing on that because it sort of is a subtle way of basically proving their hypothesis that, you know, plants are bad because you can get omega-6 from plants and it's just—there's no evidence at all that the problem is not getting the omega-3. And when you take the omega-3, the omega-6 really doesn't matter. You actually need quite a bit of omega-6. Omega-6 plays a huge role in all your cell membranes and the fluidity of them. Not getting any omega-6 is actually bad. I don't like to focus on that as much. I think like, what can you do? You can avoid vegetable oils. And why do I say that? Because like heating the omega-6 is really where it becomes an issue.

Getting omega-6 from nuts or whole foods is like, there's just no evidence that that's an issue. I mean, obviously there's people that have allergies and stuff, but like there's just no evidence. So I don't, I just don't think that's a real major point of concern. So the next obvious, I would say, out of my top— I have like 5 or 6 lists I have here— would be exercise. Big, big, big one. And this has a lot to do with the hormetic effect and hormesis, you know. And this will kind of bleed into the next factor that I think also is really important for, for lowering inflammation. But, you know, exercise causes the release of pro-inflammatory cytokines like IL-6. And what your body does to respond to that is it has a massive release of an anti-inflammatory cytokine called IL-10.

Now IL-6 is, you know, I just talked about like inflammation and there's chronic inflammation and you can have chronically elevated levels of IL-6 and you're not going to have an anti-inflammatory response to that because it's this sort of low-grade chronic inflammation. It's not enough. It's not this huge burst of inflammation that you get from something like exercise where your body is responding to that with an anti-inflammatory response. It's just little low-grade inflammation and so IL-6, it's sometimes referred to as a Janus cytokine because it can be good, it can be bad, right? It can be good if you're talking about IL-6 being elevated in response to exercise or in response to sauna because sauna does the same thing.

But we also know that that IL-6 that's elevated in response to exercise and sauna both have been shown to come with a counter-response of IL-10, which is anti-inflammatory, and the counter-response is even greater. So you're basically having a net anti-inflammatory effect, right? So exercise is one of the big ways that people can modulate their inflammatory burden. And then, kind of to just transition to the next factor, that would also be heat stress from the sauna or a hot bath or a steam shower or doing things like Bikram yoga routinely. Again, the IL-6 and IL-10, same effect with the sauna. We've talked about sauna mimicking moderate cardiovascular exercise in many ways. And so that's, that's one of the ways it does it.

But there's also evidence showing that C-reactive protein, as we talked about, you know, elevated C-reactive protein is associated with the development of atherosclerosis, arterial, you know, like arterial compliance problems. Arterial compliance means the ability of your arteries to expand and contract with changing pressure, and you want your arteries to be able to do that. If your arteries can't do that, you know, that can lead to a stroke. It can lead to all sorts of problems. And so C-reactive protein is associated, you know, high elevated C-reactive protein is associated with loss of your arteries being able to do that. And there's, there's studies showing that the sauna reduces blood levels of C-reactive protein. There's also associative studies.

So like over, you know, that the one of the big Finland studies where there was more than 2,000 people, sauna bathing basically lowered— or was associated with lower C-reactive protein in a dose-dependent manner. So the more frequent the sauna use, the lower the C-reactive protein. IL-10, also very potent anti-inflammatory. There's a study, a small study involving just 22 healthy male athletes and non-athletes, and they received 2 15-minute sauna sessions. At about, it was hot, it was like 208 degrees Fahrenheit. And this was separated by, so the 2 15-minute sessions at 208 degrees were separated by a 5-minute cooling period. And after that, their IL-10 levels like really dramatically increased. There's also heat shock proteins increasing as well. But you get the point.

Sauna also is a way to lower the inflammatory burden. And I think that it's so beneficial for cardiovascular health, for brain health, as we're going to talk about later. I also think for bone health, for skin and joint health as well through collagen synthesis with the increases in growth hormone. So we have cutting out refined sugar, we have adding omega-3, exercise, sauna. And then another one I think is important is sulforaphane. Sulforaphane is something that is found in broccoli sprouts. For people that are on more of a budget, it's probably the cheapest and most economical way to get sulforaphane is to grow your own sprouts. You can go for the store-bought ones in a pinch, but the risk is twofold. One, they may be on the shelf too long and there may be bacterial contamination.

At that point, and two is that they're on the shelf too long and the sulforaphane level is just not as concentrated as it would be if you were to eat the sprouts right after growing them when the sulforaphane is much higher. So sulforaphane has been shown— so there's been animal studies showing that it can basically inhibit the activation of a powerful inflammatory pathway called NF-kappaB, but there are also other studies showing in humans that healthy people that took about 14 grams of cruciferous vegetables per kilogram body weight per day, they decreased their circulating levels of IL-6 by 20%. So again, it's that low-grade— it's the bad IL-6. So, you know, it's the IL-6 that's that, you know, chronic— associated with that chronic low-grade inflammation.

20% is a pretty— that's a pretty significant drop. It's actually pretty impressive, but it's also quite a bit of cruciferous vegetables these people were eating. There was another study that showed that a broccoli sprout powder extract containing about, I would say, between 30 and 40 milligrams of sulforaphane, that's an amount that if you were actually eating fresh broccoli sprouts, you could eat about 100 grams of the sprouts and get about 40 milligrams of sulforaphane. So that study showed that TNF-alpha, which is a very powerful cytokine involved in aging and cardiovascular disease, all sorts of problems, Alzheimer's disease, it lowered that inflammatory marker by 11%. It lowered C-reactive protein by 16%. And so that's also pretty robust.

And then there are associative studies in humans showing that basically the top 20% of people that— basically the top 20% of consumers of cruciferous vegetables, again, cruciferous vegetables, broccoli, cauliflower, cabbage, you know, collard greens, these are vegetables that contain sulforaphane. So the top 20% of consumers of those types of vegetables had on average lower, a 25% lower IL-6 and 13% lower TNF-alpha compared to the bottom 20% consumers of cruciferous vegetables. So I do think that consuming the cruciferous vegetables and, you know, through broccoli sprouts would be the best way. Moringa powder could be another way to do it. And then there's also supplements.

And there's a question— there's a rapid-fire question later about what I think about different types of sulforaphane supplements that I'll get to. But so that's the other one. Time-restricted eating is another one. So time-restricted eating, there was a study showing that after 12 months of time-restricted eating, body mass and fat mass were lower compared to people that had a normal diet, but inflammatory biomarkers, so IL-6, IL-1 beta, TNF-alpha, which I just mentioned, were significantly lower and improved after doing time-restricted eating for 12 months, so like a full year. There's other, like cholesterol improved, LDL was lowered, HDL went up, fasting glucose was improved. So there's a lot of different biomarkers that were improved.

Time-restricted eating, really, there's a lot of ways to do it, but I think the main and easiest way to think about it is basically you want to stop eating a minimum of three hours before you go to bed, and that usually ends up being like eating all your food probably within like a ten-hour window. Some people do eight hours as well, but like basically you want to have a period of rest, a period of your body has to not be digesting in order to go into repair mode. And if you're not going to have that repair mode, then you're basically— I mean, if you're not going to have that not-digesting mode, you're basically not going to go into repair and that's kind of a problem because you need to be repairing all sorts of damage that's accumulating throughout the day. Okay.

And then I would say the last factor, again, I have a little bit more than 5. Let's see, what did I have? Cut out refined sugar, high omega-3, exercise. Sauna, sulforaphane. So I have 7: TRE. And the other one that also affects inflammation would be lower on my list—do the others before this. Cold exposure also reduces inflammation. I say to do the others first because of all the other health benefits associated with doing time-restricted eating and sauna and sulforaphane. Omega-3. It's just, it's not just inflammation, right? Like, there's, there's so many different important and beneficial things going on with these, with, with these, uh, various lifestyle factors and supplements.

But, um, cold exposure is another one, a lot easier to do now when it's really hot. In fact, I probably will be getting in my cold plunge today. It's been super, super hot in Southern California. Uh, norepinephrine, which is one of the major, most repeatable, most robust responses to cold exposure actually reduces inflammation. I don't know that a lot of people know that, but depending on the temperature of the water and the duration that you're in it, you can have up to a 5-fold increase in circulating norepinephrine levels. So they can really go up. And really just 20 seconds at 50 degrees Fahrenheit can boost norepinephrine twofold. So you don't have to stay in for 20 minutes, right? I mean, you know, obviously you can start to build up some adaptation.

And I've noticed this with myself. So for example, when I'm routinely doing my cold plunge, it's absolutely not as painful. I can stay in there longer, you know, but when I stop doing it for even like a couple of weeks, it— I have to start from the beginning, like adapting again. So, um, part of the adaptation has to do with, you know, you're, you're increasing the number of mitochondria in your adipose tissue. This is called browning your fat. And, um, so, you know, the more mitochondria you have in your adipose tissue, the more— the easier it is to generate energy and heat as a byproduct. So you kind of feel warmer. And so it's easier for you to kind of tolerate the cold. So norepinephrine does inhibit TNF-alpha.

So that's one of the ways it lowers inflammation. But it also decreases other sort of nasty chemicals that our immune cells are secreting, like macrophage inflammatory protein-1 alpha. And so, you know, like when you're— and by the way, that macrophage inflammatory protein I just mentioned plays a major role in arthritis and people that have arthritic pain. That's a target. And so it's probably why there's been quite a few studies looking at cold exposure from, you know, the cold water immersion and also from cryotherapy and how it seems to help people with arthritis because it's likely affecting the macrophage inflammatory protein-1. I haven't seen anyone directly measure that. I'm sort of connecting the dots.

Norepinephrine is known to be increased by both doing cryotherapy and doing cold water immersion. And norepinephrine is known to lower macrophage inflammatory protein-1 alpha, but no one has directly tested this in people with arthritis by doing cold exposure and then measuring their actual levels, which that would be a good study to do, but it just hasn't been done. So those are my top 7. I know you asked for 5, but I think that those are the top ones that I would— that I think are the biggest bang for your buck and also have other health benefits as well. It's not just inflammation. So that's kind of my list.