
Inflammation might be the root of preventable disease - bookofjoe
https://harvardmagazine.com/2019/05/inflammation-disease-diet
======
Someone1234
I found this area interesting:

> “A fat cell is almost like a primitive immune cell,” says Hotamisligil. “It
> can request the assistance of immune cells when in trouble, but if the
> stress continues, and the immune cells remain, they start changing their
> character and behavior from helpful to harmful.”

...

> When overloaded with stored lipid, fat cells begin to lose their functional
> and structural integrity and may start spilling their toxic cargo. When
> cells fail like this, the immune system kicks in, initially to assist in
> clean-up. Macrophages engorge themselves on the leaking fuel, and may die
> themselves during this process. But in the long run, what is meant to be a
> mutually beneficial interaction between the metabolic and immune systems
> turns into a very dangerous and harmful relationship. Obese individuals thus
> live in a state of chronic stress and inflammation; in fact, many people do,
> because their energy intake vastly exceeds their needs. Hotamisligil calls
> this chronic energy overload, and the resulting abnormal immune response,
> metaflammation: metabolic inflammation.

This article brings together a whole host of different areas of research about
human inflammation. I would recommend reading it, but it isn't an article you
can skim and there's no big bang conclusions, just more areas of keen research
and exploration.

~~~
andai
> Critics might suggest that inflammation is just a symptom in these diseases,
> rather than a cause. But Hotamisligil says, unequivocally, “Chronic
> inflammation is uniformly damaging and is absolutely causal to the process,
> because if you interfere with it, you can reverse the pathology.” And this
> ability to control such diseases simply by reversing inflammation is a
> biological response, dating far back to the time of a common ancestor, that
> has been retained across diverse species of animals to the present day, he
> says, pointing to experimental evidence: “If you can make Drosophila [fruit
> fly] diabetic, and then block the inflammatory response systems, you can
> cure diabetes in Drosophila, the same way you can reverse it in the mouse,
> in primates, and in humans, provided that you do it with the right tools. Of
> course, the higher the organism, the more complex these pathways are, so it
> takes more effort to define the precise mechanisms to manipulate.”

~~~
splittingTimes
So what are the "right tools" to reverse diabetes in humans?

These are probably different for the different types. (When young, non-obese
kids get it, I doubt it's because of energy surplus)

~~~
mtw
Im pretty sure this is for type 2 diabetes. To reverse, you have to loose
significant weight which is at least -20%, sleep well, exercise regularly, and
eliminate stress

~~~
0xcde4c3db
> you have to loose significant weight which is at least -20%

I think that's an oversimplification. Roughly a third of people with T2D have
a normal BMI, and most obese people don't have T2D. I mean, sure, lose the
weight if you can afford it, but that's attacking an exacerbating factor
rather than the root causes (which are not really understood yet).

~~~
magnamerc
Huh? Losing weight requires less resources (money) than maintaining it, you
just simply stop eating and fast. Proper nutrition and hormone regulation to
maintain your lower body weight is a different question, but even that should
be cheaper or the same amount of money given that you're reducing your overall
caloric intake, even though the food you purchase may be slightly more
expensive.

Also, the root causes are fairly well understood at this point. Yes, genetics
play a role (sometimes a large on), but if an individual eats a balanced
mostly plant based diet, exercises, and gets enough sleep (minimum 8 hours),
then the likelihood of getting T2D reduces significantly. If someone has T2D,
they are almost assuredly lacking in one of those three areas.

~~~
js2
Parent wrote “Roughly a third of people with T2D have a normal BMI.” Those
people can’t “afford” to lose weight not in the dollar sense, but because they
have no weight to lose.

------
rossdavidh
My prediction: 1) reducing chronic inflammation by, for example, exercise or
eating better food, is proven to have good health effects 2) pharmaceutical
companies try to make that into a pill 3) dang, the benefits of the pill are
not nearly as big as if you exercise and eat better food, and not nearly as
big as our early trials of the drug indicated they would be 4) we must need a
different kind of pill

~~~
braink
Bottom line: pharma sells pills to make money; they don't make money off of
healthy people who don't take their pills. So long as we link the health
industry to making profit, we are prioritizing profits over health.

~~~
skookumchuck
Profits are what drives innovation in pharmaceuticals.

~~~
bandushrew
That is a truism, right? Currently in the US we have private pharmaceutical
companies driven by a profit motive, so profits are what drives their
innovation.

Setup a different system, and other motivations will drive their innovation,
right?

Unless your claim is that innovation can only EVER be driven by profit?

~~~
fastball
I thing the argument is more along the lines of:

1\. Observed value drives innovation.

2\. Profit / profit-motive is one of the most straightforward / most efficient
means we have to observe value.

~~~
Swenrekcah
You’re probably right and my counter argument would be:

1\. Human [curiosity, desire, necessity] drives innovation.

2\. Profit mandate suppresses most of those innovations by promoting the few
money making ideas (however beneficial or harmful they may be).

~~~
fastball
I think the issue with that response is that [curiosity, desire, necessity]
are all just specific versions of "observed value" which you are then applying
to oneself. Sure, you'll have a lot of innovation if everyone is trying to
satisfy _their own_ curiosity, desire, or necessity. But you'll drive far more
innovation if you have individuals who are also concerned with satisfying
those needs for _other people_. And the easiest proxy for "someone else
desires or needs this" is pricing mechanisms. Luckily, the internet / better
communication methods are making it much easier to determine what is valuable
to others without pricing mechanisms, but I would argue that profit motive is
still the most effective method.

~~~
Swenrekcah
Yeah, I mostly agree. Profit motive is not a terrible method on average. I
just get a bit worked up when I encounter any variant of “a corporations only
duty is to create shareholder value”. :)

------
alchemism
In this context, I find it interesting that popular ‘folk’ remedy herbs in
many regions are ones which reduce inflammation, e.g. chamomile, rosemary,
yarrow.

Also many of the ingredients in curry powder, e.g. turmeric, ginger,
fenugreek, black pepper have inflammation-fighting properties. Curry powder is
traditionally best used within a few weeks of grinding the ingredients
together; it may not be the taste which subsides in this time, but the other
properties.

~~~
Aromasin
I'd be interested to see if there's a study comparing inflammation in India to
the West. Closest I've found is a study on rising rates of IBD there, I assume
as they begin to adopt a Western diet [1].

[1]
[https://www.karger.com/Article/FullText/465522](https://www.karger.com/Article/FullText/465522)

------
arkades
I find these sorts of arguments to be... odd.

“Inflammation” includes so many normal homeostatic processes that it’s
essentially a tautology to point to inflammation as being a critical component
of disordered homeostasis. The biggest key as to whether a molecule is
considered inflammatory is what type of biologist discovered it first.

~~~
blotter_paper
>The biggest key as to whether a molecule is considered inflammatory is what
type of biologist discovered it first.

I'm super ignorant of this field. Do you have examples of molecules that would
be classified differently if found by different researchers?

~~~
goldenkey
I think what they are referring to is molecules like Cytokines [1] which are
found in responses to [infection, immune responses, inflammation, trauma,
sepsis, cancer, and reproduction] (from Wikipedia)

Inflammation and immune response seem entirely connected.

[1]
[https://en.wikipedia.org/wiki/Cytokine](https://en.wikipedia.org/wiki/Cytokine)

~~~
User23
Don't forget exercise in that list.

~~~
andai
Also digestion, depending on what you ate.

------
Roaexus
Eating a whole foods planet based diet can reverse diabetes and significantly
reduce inflammation.

I didn't believe this until I had a dear friend pass away from a heart attack
at 33. This forced me into getting my blood work done. I was astonished how
bad my numbers looked across the board even though I was skinny.

By eating a planet based diet all my numbers have normalized. I eat and sleep
better. My energy has increased. I take 0 drugs. It's been a really eye
opening experience. I'm 38.

The standard american diet needs to be fixed. It should look more like this

[https://food-guide.canada.ca/en/](https://food-guide.canada.ca/en/)

[https://www.health.harvard.edu/staying-healthy/foods-that-
fi...](https://www.health.harvard.edu/staying-healthy/foods-that-fight-
inflammation)

[https://www.health.harvard.edu/blog/eat-more-plants-fewer-
an...](https://www.health.harvard.edu/blog/eat-more-plants-fewer-
animals-2018112915198)

Book recommendation - How not to die - Michael Gregor

“Let food be thy medicine and medicine be thy food.” ― Hippocrates

~~~
ZeroFries
Neptune is my favourite snack.

------
LinuxBender
In my case, inflammation is a side effect of insulin resistance, like my
fellow 83 million Americans with metabolic syndrome. If I can reverse the
cause long enough, the liver should stop dumping fat into the adipose tissue
and triglycerides may drop.

~~~
the_economist
I did a 5-day fast last month. Water only, 120 hours.

In the 30 days since I completed the fast, my fasting blood glucose has
dropped from ~80-90 down to 65-75.

I'm concerned about the accuracy of my Freestyle Libre, but it was previously
consistent with professional labs.

Anyway, a long term fast like the one I did may help improve your insulin
resistance; it seems it did for me.

~~~
copperx
As someone with a fasting glucose of 95-99 (my GP isn't concerned, I'm not a
diabetic), I wonder why would you want to reduce fasting glucose if it's not
even in the prediabetic range?

~~~
the_economist
[https://chriskresser.com/when-your-normal-blood-sugar-
isnt-n...](https://chriskresser.com/when-your-normal-blood-sugar-isnt-normal-
part-1/)

In this study, people with FBG levels above 95 had more than 3x the risk of
developing future diabetes than people with FBG levels below 90:
[https://www.amjmed.com/article/S0002-9343(08)00231-3/fulltex...](https://www.amjmed.com/article/S0002-9343\(08\)00231-3/fulltext)

This study showed progressively increasing risk of heart disease in men with
FBG levels above 85 mg/dL, as compared to those with FBG levels of 81 mg/dL or
lower:
[https://www.ncbi.nlm.nih.gov/pubmed/16207847](https://www.ncbi.nlm.nih.gov/pubmed/16207847)

------
RobertRoberts
How can a symptom be the "cause" of a disease?

Gingivitis is "inflammation of the gums", but it's "caused" by bacteria,
plaque, tarter, etc... inflammation is the description of what is happening
(ie, symptom) not the "cause".

~~~
tim333
The gum disease thing is actually one of the best bits of evidence for the
inflammation does bad stuff hypothesis:

>People with gum disease (also known as periodontal disease) have two to three
times the risk of having a heart attack, stroke, or other serious
cardiovascular event. [https://www.health.harvard.edu/heart-health/gum-
disease-and-...](https://www.health.harvard.edu/heart-health/gum-disease-and-
heart-disease-the-common-thread)

The idea is bacteria in the gums cause inflammation (red swollen flesh, more
white cells, metabolic changes) causes clogged arteries causes heart attacks.

~~~
RobertRoberts
The symptoms of gum disease (a generic term) can be inflammation (I am not a
dentist). But suppressing the symptom of inflammation doesn't cure gum
disease.

------
whatshisface
At the same time, anti-inflammatories slow wound healing. Here are a couple of
random studies I found.

[https://www.ncbi.nlm.nih.gov/pubmed/17319622](https://www.ncbi.nlm.nih.gov/pubmed/17319622)
[https://www.ncbi.nlm.nih.gov/pubmed/22381097](https://www.ncbi.nlm.nih.gov/pubmed/22381097)

~~~
cr0sh
Something I experienced about 20 years ago - I threw my back out (just was
sitting, and turned my torso - and that was it), major sciatica pain.

Went to the doctor. I was prescribed a certain stretching exercise, plus also
800mg ibuprofen, bed rest, etc.

I was popping the ibuprofen "on schedule" \- 3x a day. At first, it helped
some, and so did the exercise. But then, the pain came back, and nothing was
cutting it. Not the stretching exercises, not the ibuprofen; this was after a
few weeks of doing all of this.

So I decided that since the ibuprofen wasn't helping, to just drop it. And I
continued with the exercise.

...and the pain went away. I haven't had a major problem with my lower back
since then (knock on wood).

My anecdotal theory is that somehow, the anti-inflammatory drug was preventing
healing at high doses, and I had to quit it to get better.

I don't know if that is really true or not, all I know is that was what seemed
to do the trick for me.

~~~
justinator
Inflammation can be a signal to the body to heal an area specifically
expressing the inflammation. Many treatments involve causing additional damage
to the wounded area to promote inflamation. This is good!

Its _chronic_ inflammation that's not good.

~~~
joncrane
Isn't this the concept behind dry needling?

~~~
justinator
I do believe so.

------
openforce
I found the last part about SPMs and anti-inflammatory molecules, very
interesting and encouraging. Being a colitis patient, I have found out in my
own experiments, that eating a diet rich in well sourced fish and chicken
decreases my inflammatory symptoms and is very filling at the same time.

~~~
craz8
I found that gluten irritated my Crohns.

I recently started Remicade - it reduces the immune system to try to stop the
auto-immune problem that is Crohns. It was eye opening what other little aches
and pains went away once the immune system was turned down a bit and the
inflammation was lowered

Certainly the extra inflammation was causing other problems where the
inflammation is the main cause.

~~~
rorykoehler
How has this affected other critical processes of the immune system such as
fighting infection?

------
mleonhard
Is this a PR piece paid for by Novartis, the makers of Canakinumab? Wikipedia
says the drug costs $8k/week and the initial study showed no survival benefit.
Then "further analysis" showed a big benefit. Something seems off.

[https://en.wikipedia.org/wiki/Canakinumab](https://en.wikipedia.org/wiki/Canakinumab)

~~~
zwkrt
Inflammation can also be heavily reduced for "free" with a lifestyle change
though, so I'm not exactly buying it.

~~~
taneq
Yeah but who's going to do _that_?

------
tomohawk
> “My papers were rejected,” he recalls; “my grants turned down.”

Why scientific "consensus" is not scientific.

------
Tharkun
It's curious that the article doesn't mention allergies. AFAIK those have been
on the up for decades, with more and more people being allergic to trivially
common things (pollen, dust mites,...). Allergic reactions can be a cause of
things like asthmatic symtoms. Seems to tie in with the inflammation thing.
Maybe it's part of the cause? Or maybe they're themselves another symptom of
this proposed chronic inflammation?

------
rsync
Inflammation ? Fasting. Just try it. It costs nothing.

~~~
hoseja
Except major performance decrease. Some people cannot afford that.

~~~
Aromasin
Anecdotally I found my performance to - both in the gym and in the office -
increase not decrease. From athletes and academics I follow on social media,
they also say the same. I've read a few hypothesis as to why this may happen.
In an evolutionary sense, when in a fasting state we would require more energy
to go out and hunt/gather food to take us back out of that state. IIRC,
metabolism increases while fasting. It wouldn't make sense for our body to
reduce performance because that just makes starvation an even more likely
possibility, as it suddenly becomes much harder to go out find a food source
due to said >"major performance decrease".

There are a few studies knocking around about regarding it, but I've only got
a minute so this is the best I could do for the moment-

"Findings indicated that pre-exercise feeding enhanced prolonged (P = .012),
but not shorter duration aerobic exercise performance (P = .687). Fasted
exercise increased post-exercise circulating FFAs (P = .023) compared to fed
exercise."[1]

[1][https://www.ncbi.nlm.nih.gov/pubmed/29315892](https://www.ncbi.nlm.nih.gov/pubmed/29315892)

~~~
avinium
How long are your fasts?

I experimented at the start of the year and didn't experience any drop in
performance - office or gym - with water fasts less than 24 hours.

Fasting between 24-72 hours, though, really affected my sleep and made me feel
weaker during workouts (though it didn't really affect me mentally). Curious
to see if others experienced the same.

Can't comment on longer fasts as I didn't exceed 72 hours (though I did read
many reports of it actually getting _easier_ after that point in time).

Currently doing IF (very rough 20/4) which is working pretty well.

~~~
Aromasin
Honestly it varies massively - I play it by ear, as it's normally interrupted
by going out to dinner with friends or dates.

I fast once every 10 days minimum (arbitrary number, but it keeps me
disciplined). If I've had a few weeks of excess (lots of drinking and greasy
takeaways) I might do 3-4 days. At least 2-3 times a year I like to do a 6-8
day fast. I've done this for the past 4 years and I've felt remarkably better
for it, with the most noticeable thing being reduction in scar tissue (from
surgery) and inflammation symptoms.

In terms of how it makes me feel while fasting, it depends on the day. A one
day fasts tends to make me just feel hungry around meal times, assumedly
because I'm still largely running on the glycogen in my muscles. I used to
find day 2 pretty rough, as I'm guessing that's how long it would take for the
process of ketosis to start in me. As your body adapts to frequent fasting
though it becomes plain sailing though. I'll often arrange my fast to coincide
with a large stint of work, as I feel my mental clarity is much higher - akin
to taking Modafinil if you've ever tried it. Hunger isn't an issue for me at
all once I'm in a state of ketosis.

I highly recommend doing an extended fast at some point. If anything it allows
you to become much more satiated by smaller portions, and it eliminated any
sugar cravings I used to have.

------
ensiferum
I'm quite sure eventually this will all align with the research into sugar
which basically says that sugar is poison. Especially in the quantities that
the modern people eat these days.

Dr Lustig has done the sugar research.
[https://www.youtube.com/watch?v=dBnniua6-oM](https://www.youtube.com/watch?v=dBnniua6-oM)

------
fnord77
> “To treat excessive inflammation...we don’t want to block the inflammatory
> response. We want to stimulate the resolution pathways.”

------
tracker1
It's worth noting, that despite being blocked out in the diet list in the
research, the state of red meat is still not firm [0]. There seems to be a
body of evidence that naturally fed ruminants are very good sources of
nutrition for people. It's worth noting said nutrition profile does change
DRAMATICALLY when they're fed unnatural sources (grain/feed) over natural
sources.

If you don't eat meat because you don't want to for whatever reason, but there
is a _LOT_ of bias in food research.

In general, avoid refined sugars, avoid refined seed oils, avoid other
refined/processed foods... increase intake of less processed (even if cooked)
foods, and try to eat fattier fish 3-4 times a week.

[https://chriskresser.com/does-red-meat-cause-
inflammation/](https://chriskresser.com/does-red-meat-cause-inflammation/)

------
joduplessis
This is interesting! Bit of an anecdotal story, but I struggled with weight
issues until about 8 years ago & I've often spoken to friends saying that it
really felt like I ALSO suffered from some type of body inflammation. Even on
"binge-y" days now, the morning after my sinuses go nuts! Super interesting
read.

~~~
jimijazz
Can you share what you did do to improve your condition?

------
katakuchi
I often wonder about the use of herbal medicine instead of our artificial
pharmaceutical cousins to combat inflammation. It just seems so arbitrary,
counter-productive and ironic to fill your body with more toxins to counter
the inflammation achieved by overconsumption of primarily 'bad food' in the
first place.

------
mikedilger
That study they cite: 3 of 4 dose levels didn't meet the statistical
significant threshold, and in the one that did there was no difference in all
cause mortality.

Look, I wish it was as simple as a single easily treatable vector like
inflammation. But it's not. Life is not simple.

------
abledon
What is inflammation really? Is it an excess of energy around that area? E.g.
extra positive charges ?

~~~
projektfu
I learned it as "rubor, tumor, calor, dolor, et functio laesa" meaning
redness, swelling, heat, pain and loss of function. These are the classic
signs and the reason it gets its name, as it's like a fire in the body. But as
other commenters have said, it now seems to be the presence of certain
signalling molecules or cell types that are associated with inflammation, and
when people speak of it they may not be referring to any of the classical
signs of inflammation. Which is a shame because now its lost the helpful
etymology.

~~~
abledon
I'd like a physics level explanation.. when those molecules are there? whats
going on at the atomic level, is there an excess of negatively or positively
charged molecules ? When there is inflammation, there is usually heat, and
heat means energy.

~~~
projektfu
Lots of things can be going on. One of the most dramatic things is the
respiratory burst of neutrophils.
[https://en.wikipedia.org/wiki/Respiratory_burst](https://en.wikipedia.org/wiki/Respiratory_burst).
But neutrophils are not the only inflammatory cell and not all inflammatory
processes involve them. There is way too much to describe in a comment on the
internet.

------
baccheion
50-100 IU/kg vitamin D3. 10 mg/kg (chelated/TRAACS) magnesium.

------
peter303
More like a co-sympton. Whatever cures the disease cures the inflammation.

Unexplained inflammation might be sign of an undiagnosed condition.

------
forgotmypw
What causes inflammation?

There are ingredients in most commonly sold processed foods that are level 1,
2, and 3 on the hazmat scale.

~~~
IAmGraydon
Name them.

~~~
forgotmypw
Here's one, grandfathered in 1958...

[https://en.wikipedia.org/wiki/Sorbic_acid](https://en.wikipedia.org/wiki/Sorbic_acid)

For the rest, just pull on the wiki-thread.

------
m3nu
More reason to keep an eye on hsCRP and take steps if it gets too high. (Most
labs use <1 mg/L as limit, but small injuries already raise it to 0.4 for me.
So 0 to 0.2 is probably desirable.)

The article brings together different issues, like fasting, fat tissue,
exercise, diet, sugar and chronic disease.

Reposted with a summary here:
[https://www.reddit.com/r/ketoscience/comments/bh2s9a/could_i...](https://www.reddit.com/r/ketoscience/comments/bh2s9a/could_inflammation_be_the_cause_of_myriad_chronic/)

~~~
atomical
This sounds like pseudoscience. Our lives are becoming dominated by fads and
gurus just like our forebears.

~~~
m3nu
Agree with what you say in general, but not here. hsCRP is fairly well
studied.

~~~
atomical
What are you disagreeing with? Do you believe people should have hsCRP tested?

A cursory search reveals it's associated with heart disease. But for most
people heart disease can be diagnosed with other blood work.

There was a blog posted to HN about a man whose Apple watch told him he had an
irregular heartbeat. His resting heart rate is 120. He doesn't need an Apple
watch to tell him something is wrong!

I'm wondering if hsCRP is more pointless data gathering.

------
babkayaga
As with any news article that includes "may" \- reader should remember to add:
"... but probably isn't".

~~~
rhizome
I'm a bit concerned that the comments here are so credulous. "Inflammation"
has been part of the woo-woo arsenal of certain corners of the health and
wellness community for at least a couple of decades, and which I wouldn't be
surprised if it supplies a not-insignificant number of the anti-vax adherents.
It's that specious.

~~~
perl4ever
That sounds like "Hitler was a vegetarian, hence vegans are Nazis" logic.

~~~
rhizome
It isn't. If it were instead, "vegans talk about Hitler all the time, so..."
then it would be an apt analogy.

------
baxtr
_> People already know what they should be doing—but for most, that knowledge
doesn’t change behavior. Humans are hard-wired to conserve energy (see “Born
to Rest,” September-October 2016, page 9), for example, and to prefer foods
that are fatty, salty, and sugary.

This suggests that pharmaceutical interventions that block inflammation may be
necessary to check the global epidemic of non-communicable disease._

Really? What about side effects? Why not work on becoming smart instead of
telling people to eat pills?

~~~
frankzinger
> Really? What about side effects? Why not work on becoming smart instead of
> telling people to eat pills?

From the end of the article:

“To treat excessive inflammation, whether it is chronic or the result of an
acute tissue injury, we don’t want to block the inflammatory response. We want
to stimulate the resolution pathways.”

~~~
frankzinger
I realise my comment wasn't very clear. The way the article recommends to
stimulate the resolution pathways does imply the possibility of such drugs in
the future, but primarily they explain that consuming chicken, beef, eggs,
fish, and fish oil or algae (for omega-3 EDA and DHA) will promote the
synthesis of these substances in one's body.

Overall they are definitely not promoting the use of drugs over lifestyle
improvements. They talk about lifestyle improvements throughout the article
and this was my primary takeaway: exercise regularly; don't overeat; eat those
things mentioned above.

