Why You Feel Depressed Even When Nothing Is Wrong | Dr. Rhonda Patrick

Depression is interesting. There's a pretty classic study that no one ever talks about where healthy individuals were injected with lipopolysaccharide. So for those listening, this is a component of your bacterial outer cell membranes. It's present in our. In our colon, because we have about, I don't know how many trillions of bacteria, like so many bacteria in there, right?

40 or 50 trillion.

Okay, 40 or 50 trillion. There's about a gram of lipopolysaccharide in our gut because those bacteria do die off.

And these are bacterial toxins. This is what pisses off your immune system to. No way.

It does. And when we have gut permeability, lots of things that cause that leaky gut, it releases. Right. Also known as leaky gut, it leeches the LPS into our bloodstream. Well, this study took healthy individuals and injected them with an amount of LPS that would be equivalent to something that you could get from intestinal permeability. And it caused depressive symptoms in these individuals. Okay. One that links inflammation to depression. 100%. Two, if those individuals were given EPA. So this is one of the omega 3 fatty acids. It does play a major role in dampening inflammation through a variety of mechanisms, like resolvins and marisons and the SPMs. These are all molecules that are resolving inflammation very quickly. They did not experience those depressive symptoms.

Yeah.

If they were injected with the LPS.

If they got Omega 3s, if they.

Have the Omega 3s. So it comes down to, like, again.

You know, and Omega 3s have been shown to actually help with depression.

They have.

And add.

They have. Yeah. But depression, specifically epa, seems to be very important for depression. And I think that's because there's a really big inflammatory component to depression where, you know, there's now studies showing that people that don't respond to classical SSRIs. So serotonin reuptake inhibitors like Prozac. Exactly. People that don't respond to that typically have very, very high levels of C reactive protein. Inflammation. So there's like a subset of people, some people respond and it helps them, but there's a subset, a quite large subset of people that have very high inflammatory biomarkers and do not respond to SSRIs. And so logically, the next question would be, should we lower their inflammation? How can we lower their inflammation?

I read some paper that was like, hypothesizing that we should use TNF alpha blockers, the biologics for depression. In other words, these are drugs that massively suppress inflammation in the body used for serious autoimmune diseases and they're talking about using it for depression. I'm like, wait a minute, like how about we find out why there's inflammation in the first place and get to the root cause of it, which is really what we do in functional medicine. I think what you're kind of hitting on just sort of peripherally and I want to sort of tie the dots together, is that when you don't have enough of the right nutrients and you don't have a proper functioning metabolism, there's a lot of downstream consequences. You get inflammation, you get oxidative stress and you get damaged mitochondria and you get DNA damage. And you look at these processes, these are the fundamental things that have to be working for you to be healthy across every organ, across every disease state. And it's what we're now calling hallmarks of aging or including many of these things. And what you're talking about is. And Bruce Ames figured this out even before there was a word hallmarks of aging. He figured out that these nutrients are critical in these pathways that degrade and become problematic as we age, but that we can offset that and actually take longevity nutrients and get a quote metabolic tune up. And he's even talking about things that I think are, we don't think of typically as essential nutrients that are we call conditionally essential nutrients. And whether it's carnitine or taurine or things that may not be kind of a typical deficiency disease vitamin or mineral, but that are still really important for our biological functioning and we're still low in them. So I have this theory, I want to come back to it a minute. About that I kind of made up called symbiotic phyto adaptation which is a big mouthful, but essentially it means that we've co evolved with plants to borrow their phytochemicals to regulate key pathways in our body so we can stay healthy and that without them we don't get a deficiency disease. Like you don't get like, you know, like broccoli deficiency, but, but actually we kind of do because the phytochemicals like sulforaphane or the glucosinolates or isothionates, these are, these are molecules that regulate key pathways in our body, for example liver detoxification or removing heavy metals or whatever, controlling oxidative stress, they work to actually facilitate these, these pathways. And so I kind of this theory that it's more than just like essential vitamins in the minerals. There's a whole bunch of Stuff that's essential if you want to be really healthy.

I completely 1000% agree.

I think they just made this up.

But so I think that humans, we evolve to eat of plants and meat and things, but plants, because of the phytochemicals, you know, there are. So you mentioned sulforaphane, right? So sulforaphane is present in a variety of cruciferous vegetables like broccoli. It's much more. It's not present, I'm sorry, the precursor to it, glucoraphanin, is present in it, and it gets converted into sulforaphane when the plant matter is broken, chewed, because it activates an enzyme called myrosinase, which converts glucoraphenate into sulforaphane.

Big mouthful of words. But essentially, when you chew your broccoli, you get cool chemicals that help your body.

Exactly. And if you go even further and chew the young plant, the broccoli sprouts, there's about 100 times more glucoraphanin in it.

Damn. I'm trying to grow broccoli sprouts and I keep trying to forget and then I gotta get back on that.

Yes, broccoli sprouts are really, really high. And in glucoraphanin, I also take a supplement that's been used in a lot of clinical studies called Avocol. I don't have any affiliation with them, but they've got a really great method of stabilizing that myrosinase enzyme, which is very unstable. It's also very heat sensitive. But before I get sidetracked, sulforaphane is the most potent dietary activator of what's called transcription factor in our body. It's NRF2.

Yeah.

And this is NRF2. Yeah. It's a master regulator of, as you mentioned, detoxification enzymes. So they're called phase two detoxification enzymes, also phase one biotransformation enzymes. So those are enzymes that will convert pro carcinogens into carcinogens. So NRF2 activation will blunt that. It'll stop that from happening. So think things like nitrites being converted into nitrosamines. So nitrites are present in a lot of processed meats. And so NRF2 activation, typically it's like it gets activated every 80 minutes or so inside of our cells. But if you take sulforaphane, it gets. Sorry, it gets activated every 130 minutes. But if you take sulforaphane, it gets activated like every 80 minutes. Something like that, where it's like you're getting like a 60% increase in the activation of this important transcription factor which is regulating just hundreds of different genes that are antioxidant, involved in antioxidant function, anti inflammation. Clinical studies showing that if you give someone broccoli sprout extract or sulforaphane or glucoraphanin, plus the enzyme myrosinase, it increases glutathione in plasma and in the brain by fmri. I mean, this is unbelievable. Glutathione, as you know, it's one of the major, major antioxidants that our body has and it's very important for the brain. Other studies in China where there's a lot of air pollution, show that people that take about 40 micromoles of sulforaphane, they start to excret some of the chemicals that are in air pollution, like benzene, which is a carcinogen. They excrete it by 60% after 24 hours. Again because the activation of the phase two detoxification.

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