
Drugs that tamp down inflammation in the brain could slow cognitive decline - chris1993
https://news.berkeley.edu/2019/12/04/drugs-that-quell-brain-inflammation-reverse-dementia/
======
lhl
Alternatively, you can quite dramatically reduce inflammation in the brain via
some simple lifestyle modifications (cutting out sugar, intermittent fasting):

Mattson, Mark P., Keelin Moehl, Nathaniel Ghena, Maggie Schmaedick, and Aiwu
Cheng. “Intermittent Metabolic Switching, Neuroplasticity and Brain Health.”
Nature Reviews. Neuroscience 19, no. 2 (February 2018): 63–80.
[https://doi.org/10.1038/nrn.2017.156](https://doi.org/10.1038/nrn.2017.156).

Pinto, Alessandro, Alessio Bonucci, Elisa Maggi, Mariangela Corsi, and Rita
Businaro. “Anti-Oxidant and Anti-Inflammatory Activity of Ketogenic Diet: New
Perspectives for Neuroprotection in Alzheimer’s Disease.” Antioxidants 7, no.
5 (April 28, 2018).
[https://doi.org/10.3390/antiox7050063](https://doi.org/10.3390/antiox7050063).

Gao, Yuanqing, Maximilian Bielohuby, Thomas Fleming, Gernot F. Grabner, Ewout
Foppen, Wagner Bernhard, Mara Guzmán-Ruiz, et al. “Dietary Sugars, Not Lipids,
Drive Hypothalamic Inflammation.” Molecular Metabolism 6, no. 8 (June 20,
2017): 897–908.
[https://doi.org/10.1016/j.molmet.2017.06.008](https://doi.org/10.1016/j.molmet.2017.06.008).

White, Hayden, Karthik Venkatesh, and Bala Venkatesh. “Systematic Review of
the Use of Ketones in the Management of Acute and Chronic Neurological
Disorders.” Journal of Neurology and Neuroscience 08, no. 02 (2017).
[https://doi.org/10.21767/2171-6625.1000188](https://doi.org/10.21767/2171-6625.1000188).

Alirezaei, Mehrdad, Christopher C. Kemball, Claudia T. Flynn, Malcolm R. Wood,
J. Lindsay Whitton, and William B. Kiosses. “Short-Term Fasting Induces
Profound Neuronal Autophagy.” Autophagy 6, no. 6 (August 16, 2010): 702–10.
[https://doi.org/10.4161/auto.6.6.12376](https://doi.org/10.4161/auto.6.6.12376).

Mattson, Mark P. “Energy Intake, Meal Frequency, and Health: A Neurobiological
Perspective.” Annual Review of Nutrition 25 (2005): 237–60.
[https://doi.org/10.1146/annurev.nutr.25.050304.092526](https://doi.org/10.1146/annurev.nutr.25.050304.092526).

This incidentally also reduces system-wide inflammation among other benefits
as well:

Houtman, Judith, Kiara Freitag, Niclas Gimber, Jan Schmoranzer, Frank L.
Heppner, and Marina Jendrach. “Beclin1‐driven Autophagy Modulates the
Inflammatory Response of Microglia via NLRP3.” The EMBO Journal, January 7,
2019, e99430.
[https://doi.org/10.15252/embj.201899430](https://doi.org/10.15252/embj.201899430).

Camell, Christina, Emily Goldberg, and Vishwa Deep Dixit. “Regulation of Nlrp3
Inflammasome by Dietary Metabolites.” Seminars in Immunology 27, no. 5
(September 2015): 334–42.
[https://doi.org/10.1016/j.smim.2015.10.004](https://doi.org/10.1016/j.smim.2015.10.004).

Yamanashi, Takehiko, Masaaki Iwata, Naho Kamiya, Kyohei Tsunetomi, Naofumi
Kajitani, Nodoka Wada, Takahiro Iitsuka, et al. “Beta-Hydroxybutyrate, an
Endogenic NLRP3 Inflammasome Inhibitor, Attenuates Stress-Induced Behavioral
and Inflammatory Responses.” Scientific Reports 7, no. 1 (August 9, 2017):
7677.
[https://doi.org/10.1038/s41598-017-08055-1](https://doi.org/10.1038/s41598-017-08055-1).

Youm, Yun-Hee, Kim Y. Nguyen, Ryan W. Grant, Emily L. Goldberg, Monica
Bodogai, Dongin Kim, Dominic D’Agostino, et al. “Ketone Body β-Hydroxybutyrate
Blocks the NLRP3 Inflammasome-Mediated Inflammatory Disease.” Nature Medicine
21, no. 3 (March 2015): 263–69.
[https://doi.org/10.1038/nm.3804](https://doi.org/10.1038/nm.3804).

Marín‐Aguilar, Fabiola, Ana V. Lechuga‐Vieco, Elísabet Alcocer‐Gómez, Beatriz
Castejón‐Vega, Javier Lucas, Carlos Garrido, Alejandro Peralta‐Garcia, et al.
“NLRP3 Inflammasome Suppression Improves Longevity and Prevents Cardiac Aging
in Male Mice.” Aging Cell 0, no. 0 (n.d.): e13050.
[https://doi.org/10.1111/acel.13050](https://doi.org/10.1111/acel.13050).

Xiao, Yichen, Wenna Xu, and Wenru Su. “NLRP3 Inflammasome: A Likely Target for
the Treatment of Allergic Diseases.” Clinical and Experimental Allergy:
Journal of the British Society for Allergy and Clinical Immunology 48, no. 9
(2018): 1080–91.
[https://doi.org/10.1111/cea.13190](https://doi.org/10.1111/cea.13190).

Bugyei-Twum, Antoinette, Armin Abadeh, Kerri Thai, Yanling Zhang, Melissa
Mitchell, Golam Kabir, and Kim A. Connelly. “Suppression of NLRP3 Inflammasome
Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and
Diastolic Dysfunction.” Scientific Reports 6 (December 21, 2016).
[https://doi.org/10.1038/srep39551](https://doi.org/10.1038/srep39551).

~~~
steelframe
Eight of those studies have been published only in the past 3 years. Until I
see a pattern of repeated results, I'm going to file these under "pop
science." "Keto is the shizzle, let's get our pubz!" Let's see what happens as
others work on repro over the next 10+ years.

~~~
whoanow
TIL the benefits of eating less refined carbs and intermittent fasting is
still up for debate to some folks.

~~~
DataWorker
Add salt, fat, coffee, wine, eggs, and about a dozen other things researchers
can’t agree on. nutrition research is hella sketchy

~~~
JMTQp8lwXL
The only fat that is really problematic is trans fats, and those are pretty
much banned most places now. Fats, from particularly protein sources, contain
more bioavailable micronutrients than fruits and vegetables.

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6d6b73
Wouldn't it be better and more effective to treat the cause of the
inflammation instead?

~~~
whatshisface
Maybe, but what's the plan to do that?

~~~
whoanow
Occasional fasting, diet, exercise, sleep, positive relationships.

~~~
qrbLPHiKpiux
Not eating inflammatory foods. Severely limit sugar, carbohydrates. Not eating
as much. Enough sleep.

~~~
antasvara
That's a misunderstanding of the article, it says that the issue is due to the
leaky blood brain barrier. The chemicals for inflammation in the body aren't
inherently bad, they're just not designed to be in the brain. Decreasing the
source of that inflammation could help but it's not the issue being discussed
here.

------
knzhou
From the perspective of a non-biologist reader only seeing popular articles,
the past ten years have been completely bewildering. Nutrition has seemingly
been boiled down to a couple of magic totems that are always simplistically
either good or bad.

Antioxidants are good.

Inflammation is bad.

Telomeres are good.

Carbs are bad.

All the "bad" things get associated with each other and anti-associated with
the good things. Carbs have less antioxidants, which prevent inflammation,
which shortens telomeres. Everything is associated in a completely mysterious
way to "the gut". Carbs are bad. Why? The gut. We read this in more words and
nod sagely. It gives me the feeling of reading a children's picture book.

Biology isn't supposed to be this simple. If inflammation were always bad, our
bodies wouldn't have evolved to do it. I'm not saying the science is wrong,
I'm sure it's well thought out, but something is getting severely
oversimplified in the leap to popular articles, to the point that I don't
trust any nutrition advice based on the pop science. Does anybody know of a
better source?

~~~
Maarten88
> magic totems that are always simplistically either good or bad.

I read a book on nutrition (forgot which) that started out with these helpful
definitions:

    
    
      unhealthy - food we statistically eat too much of
    
      healthy - food we statistically should eat more
    

Food that is unhealthy is almost never plain "bad". In small quantities it is
probably even "good". It's just that most people have too much of it in their
everyday diet.

~~~
StacyRoberts
Can someone please fix block quote on mobile?

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marcbal77
Aside from the drugs mentioned, read "Why We Sleep" by Matthew Walker and all
the natural hormonal drugs that happen when one consistently sleeps.

~~~
efoto
Not that fast. Unfortunately, "Why We Sleep" appears to be rather
controversial.

[1] [https://guzey.com/books/why-we-sleep/](https://guzey.com/books/why-we-
sleep/)

[2] [https://www.wired.com/story/stop-obsessing-over-sleepyour-
br...](https://www.wired.com/story/stop-obsessing-over-sleepyour-brain-will-
thank-you/)

~~~
pps
"I study sleep. While some of walker's claims may be hyperbolic, I think they
are within reason and justified by the important message he is trying to
convey. Too many people have begun to forego sleep in their health choices,
and he has helped raise awareness of sleep's role in our health.

Many of these criticisms are quite unfair or misunderstanding the science."

[https://www.reddit.com/r/slatestarcodex/comments/dwtr0m/matt...](https://www.reddit.com/r/slatestarcodex/comments/dwtr0m/matthew_walkers_why_we_sleep_is_riddled_with/f7mid7m/)

------
spdmn
Inflammation in all parts of the body seem to be problematic and the source of
all kinds of disease and other sorts of deficiencies. What sorts of studies
and preventative treatments are leading this field?

~~~
marcbal77
From all my readings, some natural preventative strategies seem to be: not
eating sugar or long chain complex carbohydrates and sleeping consistently a
full night of sleep (removing alcohol or caffeine cited multiple times seems
to help).

~~~
lhl
Sleep (and related, circadian health) are some super interesting topics of
emerging research. For those that like books, there are two recent ones
written by researchers in the field. Matthew Walker's Why We Sleep, and
Satchin Panda's Circadian Code that are pretty breezy reads. (there are
YouTube interviews and TED talks as well):

For those that prefer more succinct reviews and want to spelunk citations,
these are a couple good starting points:

Potter, Gregory D. M., Debra J. Skene, Josephine Arendt, Janet E. Cade, Peter
J. Grant, and Laura J. Hardie. “Circadian Rhythm and Sleep Disruption: Causes,
Metabolic Consequences, and Countermeasures.” Endocrine Reviews 37, no. 6
(December 2016): 584–608.
[https://doi.org/10.1210/er.2016-1083](https://doi.org/10.1210/er.2016-1083).

Manoogian, Emily NC, and Satchidananda Panda. “Circadian Rhythms, Time-
Restricted Feeding, and Healthy Aging.” Ageing Research Reviews 39 (October
2017): 59–67.
[https://doi.org/10.1016/j.arr.2016.12.006](https://doi.org/10.1016/j.arr.2016.12.006).

------
0898
What actually is inflammation?

~~~
tooMuchCensor
I've been a casual reader about it.

It seems to be the healing process, but it can go overboard and be counter
productive.

------
louma12
Drugs are the only cause of psychological and physical affect of the
inflammation in the brain

~~~
to1y
Stress, injury, etc

------
grabbalacious
Chronic inflammation appears to be caused by persistent self-stimulation --
eating for comfort or pleasure, not getting enough sleep, chain-smoking,
getting high, etc, without respite. So it's not really a biological problem.
It's a widespread personal problem with complex biological consequences.

~~~
ScottFree
Even if chronic inflammation was caused by self-stimulation, that still makes
it a biological problem. Maybe you meant it wasn't an inherent, biological
part of aging? If that's what you meant, then I still don't agree.

IMHO, the biggest contributor to chronic inflammation is the Standard American
Diet (lots of grains and refined foods) combined with a lack of exercise.
These things have a greater, compounding effect with age. You can't exactly
tell an 80 year old woman to start running or lift weights on a daily basis.

~~~
grabbalacious
OK, but only in the sense that a car crash is a mechanical problem (there may
be repairs to make).

 _> lots of grains and refined foods_

i.e. rather tasty! I don't think we can escape from motives here: they select
what type of diet we prefer given the choice. The market caters to that.

~~~
ScottFree
> i.e. rather tasty!

Most people don't find refined foods tasty. In blind taste tests, people
vastly prefer the old McDonalds fries back when they used actual potatoes and
fried them in lard. Then the American Government said it was illegal to use
lard for "health reasons" and they need to use vegetable oil instead. As it
turns out, vegetable oils are considerably more pro-inflammatory than lard
and, as a result, are extremely unhealthy compared to lard.

> OK, but only in the sense that a car crash is a mechanical problem (there
> may be repairs to make).

You're making a category error. Self-stimulating activities and inflammation
are orthogonal. Mechanical problems don't always cause accidents and accidents
aren't always the result of mechanical problems. Similarly, not all self-
stimulating activities contribute to chronic inflammation. Eating better will
absolutely help decrease chronic inflammation, but smoking pot is anti-
inflammatory.

PS: are you a bear or ilk? Feel free to email me if you don't want to answer
publicly.

~~~
knubie
> back when they used actual potatoes

What are they using now?

~~~
grabbalacious
I don't know but they taste like potatoes with some kind of added coating.

