Inflammation might be the root of preventable disease | Hacker News Reader

Inflammation might be the root of preventable disease

harvardmagazine.com

650 pointsbookofjoe231 comments

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.

> 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.”

Getting off-topic, but how do biologists define the "highness" of an organism?

Complexity, as in complexity of gestation, development and life cycle.

What units are used to measure complexity?

I slipped and wrote "higher eukaryotes" in relation to yeast and this is my post-doc's comments:

"that broke my heart :( other eukaryotes? multicellular eukaryotes? animals? Whatever you like, but please, no "higher", the poor yeast have been evolving for a long time and are much better than us at fermenting beers..."

<edit> This is a great paper that touches on animal complexity, see "Developmental Depth" and "Structural depth" https://www.researchgate.net/publication/228365097_Possible_...

Based on how many grams of weed it has smoked.

If you interfere with the inflammation, doesn't that still leave the problem of lipids leaking?

The idea is to also mitigate the source of the inflammation, so you both goes short term and long term.

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)

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

> 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).

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.

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.

Weight loss has worked for many if I'm not mistaken...

For type 2, more, longer and more frequent fasting. Stopping most carbs and all refined sugar. Reducing calories (through fasting or general reduction) so that weight can normalize. Hormones are overriding in this, and elevated blood glucose generally also means elevated insulin which will reduce the effectiveness of any approach to weight loss.

Extended fasting is the most assured way to help normalize glucose. Some, and expecialy over time (I'm one of these) show elevated gluconeogenesis response and will take longer to normalize under a fasting focused or very low carb (aka keto diet). Once glucose is normalized (without supplemental insulin) the weight is easier to manage/normalize as well.

It's not easy, and the longer you are diabetic (type 2) the harder it is. Supplemental insulin works against you in a lot of ways. Time restricted eating, generally, and more specifically very low carb (not overdoing protein) are good approaches.

There's a lot of supporting articles and reference linked data on dietdoctor.com and elsewhere. First, and foremost, stop all refined sugars. Second, avoid refined carbs. Third, reduce refined seed oils. Eat clean and get some fatty fish 3-4x a week. And imho clean can mean red meat from naturally fed sources, likewise eggs and fish.

the fat -> immune response is reminiscent of cardiovascular diseases too

Book recommendation - "Toxic Fat" by Barry Sears (disclosure - the father of a friend of mine). Its thesis is in line with much of the research in this article.

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

Yup! I would also predict this. You simply can’t engineer your way out of needing better living conditions.

Sometimes you’re in the conditions you’re in because of mental or emotional issues, and require the assistance of a mental health professional to get back on track (for example, overeating from emotional trauma leading to obesity and inactivity).

I predict the pill that may help with these issues is something like psilocybin along with a well trained therapist guide.

Sometimes...but not often enough for our pharmaceutical community.

Well, I would argue that actually you can, but it is extremely difficult and we aren't at that level technologically yet. Currently, the best solution for many health conditions is to optimize sleep, diet, and exercise. We will probably be uploaded into machines before a pill can replace any one of those functions.

What is your reaction when social conservatives say that there's no need for contraception or STD vaccines, because you can just not have sex unless you're prepared to accept the responsibilities of pregnancy and raising a child?

condom?

I really don't see where this has anything at all to do with what you are replying to.

There’s a theme of people avoiding responsibility or consequences by using a product. Best I can tell, GP feels that this illegitimate, and this poster feels it is legitimate to use a device or product to avoid health effects.

These two statements don't seem to have many analogies, why is this relevant?

Sorry about the downvotes you're getting, I think it's a legitimate question.

Well, if I thought that having sex for purposes other than procreation was illegitimate, I might buy that. I have the impression that some social conservatives believe that. However, I don't think that.

Also, we don't see as much industry effort to push contraception, as we do from the big pharmaceutical industries. Also, we don't see a problem of contraception not actually working; it can fail to work, of course, but most people who use contraception actually get the intended results. I believe it is far more common when Big Pharma tries to put into pill form something that could be obtained from good food or good exercise, that it does not work nearly as well.

I'd predict the pharmaceutical pill will be damaging! Our body is very smart and heals most things by itself, given the right nutrition.

The first few generations probably will be. But it'll be solved.

As much as I distrust the foundation of the comment that you are responding to, this statement is factually incorrect. All you need to do to understand why this is the case is look at current medication. It's all pretty bad, and the only reason you'd take it is because the alternative is even worse.

This sounds like some anti-vaxx reasoning.

Only partially, a lot of ailments nowadays are 'wealth diseases' caused by lifestyle and obesity.

Sounds like my personal experience, curing myself from autoimmune disease.

There will be a terrible proposal plus dangerous pill, like the idea to infuse a burger with statins to nullify the cholestrol https://www.popsci.com/science/article/2010-08/cheeseburgers...

statins have been shown to increase all cause mortality in more cases than decreasing it... giving them to most of the population is a horrible idea... our bodies need cholesterol, they produce more than we will ever consume and it's fucking ridiculous as a general marker. HDL:Triglyceride ratio is better, but still highly hackable.

This is the promise of stem cells

The most effective natural treatment for inflammation is 20 minutes a day in sauna

Source needed?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941775/

> "It has been suggested that heat stress induces adaptive hormesis mechanisms similar to exercise, and there are reports of cellular effects induced by whole-body hyperthermia in conjunction with oncology-related interventions"

I wonder if the key is simply raising the temperature of the blood. My understanding is that processes like Regenokine extract your blood, elevate its temperature (which causes it to produce natural anti-inflammatory compounds?) and then inject it back into your body. Perhaps sauna (and exercise?) are doing the same, but to a lesser degree. https://en.wikipedia.org/wiki/Autologous_conditioned_serum

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.

Profits are what drives innovation in pharmaceuticals.

Profit didn't get us vaccine against rabies or acetylsalicylic acid. Researchers did, and we have universities for that.

So there are alternatives, and probably others we didn't think about.

It was profit-seeking Bayer that found a way to make aspirin in an industrial process and put it in wide use.

"In 1897, scientists at the drug and dye firm Bayer began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines, and identified a new way to synthesize it.[2]:69–75 By 1899, Bayer had dubbed this drug Aspirin and was selling it around the world."

https://en.wikipedia.org/wiki/History_of_aspirin

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?

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.

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).

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.

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”. :)

Curiosity does not provide funding in the quantities needed. Nor does it allocate resources towards maximizing the benefit to the maximum number of people.

But neither does profit motive. Is facebook maximizing the benefit of their users? It’s more like maximizing benefits to the minimum amount of people at the expense of the maximum number of people.

> But neither does profit motive.

Sure it does. Developing a cure for 100 people will generated far less profits than a cure for 100,000 people.

It's why you see cars get better every year and constant attempts to appeal to the widest customer base possible. (That didn't happen with Soviet built cars, which tended to never improve.)

As for advertising platforms, the customers are the advertisers.

I don’t dispute that.

But in the first paragraph, the side effect is that developing a not-quite-cure treatment for 50,000 people is more profitable than both the others.

As for the last paragraph, this is perhaps the essence of the problem. The motive is profit, so we only care about the advertisers. But the users are real people too, and they are getting screwed.

> the side effect is that developing a not-quite-cure treatment for 50,000 people is more profitable than both the others.

Until someone else develops a cure and takes all your business away.

Recall that a company blinded by greed developed a cure for Hepatitis C, not a treatment.

The US leads the world in pharmaceutical innovation. Hepatitis C cure, for example. Treatment for rheumatoid arthritis (Enbrel), for another.

Socialist funded research is driven by politics, not maximizing the benefit to the maximum number of people.

Note that a lot of university research is funded by corporations.

I await your list of medical advances from the USSR.

Yes but it also skews the incentives. The cure for diabetes has little meaning to pharmas. They want to keep people alive but paying for rest of their lives. That's how money shape commercial research

> The cure for diabetes has little meaning to pharmas

Unless you're the first to cure. The income, grants, and knowledge drain in your favor? People will continue to get diabetes and a treatment will cure it.

> The cure for diabetes has little meaning to pharmas

1. ABC develops an effective treatment for diabetes, but you have to take it for life.

2. DEF develops a cure for diabetes.

Which one do you think is going to make more money? The only way ABC can make money is if a cure cannot be developed, or ABC somehow convinced the government to ban DEF's cure.

Your theory reminds me of the 1970s when everyone was sure that 100 mpg carburetors existed but the oil companies bought up all the patents for it so they could sell more gas.

That's not entirely true, a lot of the research comes from passionate students trying to make the world a better place with no intention of keeping you sick.

Additionally almost every industry is profit motivated, we wouldn't have the brightest people going into medicine unless it paid well. Ironically it doesn't actually pay well enough

Making a profit on pills is just one motivation in a very complex system of competing motivations, incentives and regulations that shape what "we" prioritise.

I think drawing conclusions from one specific motivation in isolation is too simplistic. Many other profit interests benefit greatly from a healthy population that doesn't spend all its money on useless pills.

And motivations other than profit, both personal and political, are very powerful as well.

I don't think there is much evidence that eliminating the profit motivation leads to better results in general -- on the contrary. But there is a lot of evidence from Europe that health systems with public buyer cartels can achieve the same or better health outcomes far cheaper than in the US.

Although some say that sky high US drug prices effectively subsidise those European outcomes.

> pharma sells pills to make money; they don't make money off of healthy people who don't take their pills

But insurance companies do.

American healthcare is a complex system of highly-incentivized agents. Zooming in on a single component as a synecdoche is like trying to reason how a car works by extrapolating from a fuel injector.

It’s a very limited view on any industry to think that profits and greater good cannot coexist. You say the pharma industry just makes pills so they can extract profits. The researchers at those companies who dedicate their lives in persuit of treatments for the benefits of patient would say we only make money so we can make new treatments.

That’s just semantics in the end. But it’s foolish to think that just because some endeavor is profitable is must be immoral.

> we are prioritizing profits over health.

A cure for Hepatitis C was developed by profit-seeking companies. Be careful what you're willing to throw away.

Resveratrol was such a pill/fad, with some companies going belly up eventually.

It's still an interesting compound because of it's role in regulating processes within mTOR, however getting the Resveratrol to where you need it (bioavailability) is an almost insurmountable problem.

The Japanese Ibudilast pill is a super interesting anti inflammatory pill that has very interesting research behind it . I recommend taking a look at it if ur interested is this sort of thing

It's available for sale

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.

This is a good point and I was about to write a comment to say the same. Nigella Sativa is also commonly used in many parts of Asia. It also has an anti-inflammatory property. You might be interested to read this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252704/

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

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.

If it's that prevalent, maybe it's worthy of being talked about.

>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?

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

Don't forget exercise in that list.

Also digestion, depending on what you ate.

No, that's not at all what I was referring to. Please see my response for some examples.

Oh, happily.

Interleukins are a great example, as a class. They were first discovered as signaling molecules between white blood cells (inter-, -leukins, leuko meaning 'white'). Unsurprisingly, though, just because we found types of cell-cell communication in immune cells first doesn't mean it's unique to the immune setting. Some examples:

Interleukin-1 acts as a neutrophil chemotactic agent. It attracts that group of immune cells. However, it also acts to regulate the differentiation of osteoclasts. Osteoclasts are the cells that break down bone. They're a normal part of bone physiology - bone is constantly being broken down and rebuilt, as part of the normal bone remodeling process. If this were discovered by cell biologists before immunologists, it would've been named something like "osteoclast differentiating factor". Sometimes it goes in the other direction: what was originally named "osteoclast activating factor" was ultimately renamed Interleukin-1Beta.

Interleukin-4 is primarily known for its role in regulating B-cell differentiation.. It was one of the earlier lymphocytotropic hormones fully characterized and reproduced in the lab by immunologists. However, IL-4 receptors have been found on numerous cell types, strongly suggesting its pleiotropy: human myocardium expresses an IL-4/13 type II receptor, which allows it to respond to IL4 and IL13 signaling. Lab studies suggest that this allows IL4 and IL13 to jointly regulate human heart muscle contractility and baseline metabolism (knockouts for IL-4 and IL-13 receptors have shown impaired contractility and dyssynergic heart contraction.) You can imagine if this had been discovered by molecular biologists before immunologists, this would have simply been a "myocyte regulatory factor 3" rather than "interleukin 4". There's no immediately obvious immunologic connection, outside of the broader umbrella of homeostasis (stress conditions -> inflammation, stress conditions -> increased cardiac activity.)

Moving away from the interleukins:

Tumor Necrosis Factor-alpha is a major immune/inflammatory regulatory; it plays a key role in the acute response to sepsis, induces apoptosis and cachexia, and is produced chiefly by various immune cells. It's also expressed in taste bud cells where it modulates neural responses to bitter tastes. Overexpression = stronger response to bitterness. It's postulated that this is why severely inflammatory states may be associated with taste distortion. No one really cares that much about physiology of taste, so even if the immunologists had been last to the party, we still would've ultimately classified this an inflammatory mediator.

And these are the obvious ones. There are more subtle ones, like macrophages and their associated matrix metalloproteinases. These are involved in tissue remodeling and thus wound healing, and thus kind of obviously fall under the broad heading of "inflammation," since we associate pretty much anything even vaguely related to trauma as "inflammatory." But really, remodeling extracellular matrix happens constantly in healthy tissues and is part of normal physiological activity. If I'm not mistaken, matrix metalloproteinases weren't discovered in the immune/inflammatory setting first - they were discovered as part of general cell biology.

I'd be very curious to hear what you think of the interleukin 17A and 23 blockers, like taltz and tremfya. They're being sold as miracle drugs for psoriasis, but how sure are we that they don't somehow screw up your heart or bones over the course of 10 years?

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://www.health.harvard.edu/staying-healthy/foods-that-fi...

https://www.health.harvard.edu/blog/eat-more-plants-fewer-an...

Book recommendation - How not to die - Michael Gregor

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

Neptune is my favourite snack.

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.

Go for keto + IF. It helped a lot of people.

I did. In fact that was a great start, but once you reach a certain point (in having metabolic syndrome), the Keto+IF reaches diminishing returns. It did bring me down 18 inches on the waist. The gut and hypertension will remain. In fact, my hypertension actually went up. To go further requires either Metformin or Berberine. I opted for Berberine, but time will tell.

Awesome that it worked so well for you while it did. Tip for others who may try this: don't forget to lower your macros (and, in turn, calories) an appropriate amount as your weight drops. The same diet that maintains keto at 250 lbs won't keep you in keto at 190. For much, much more: https://peterattiamd.com/

Keto is the absence of carbs. So the same diet that maintains keto at 250 will keep you in keto at 190, since it is what you eat, not how much you are eating. But you are absolutely correct that one must change their caloric intake as they lose weight if they want to keep losing weight.

Are you saying someone on keto can eat 4,000 calories of butter and not gain weight?

The wording is a bit awkward, but if you re-read what he wrote, it's not what he's saying at all.

Because a ketogenic diet depends the amount of carbohydrate restriction that will cause your body to physiologically be generating ketone bodies (eg, say less than 20g of net carbs), even at a constant formulation that doesn't change (as your TDEE changes) you will still be in the same state of ketosis - eg, if you measured your mmol concentration of BHB, it would likely remain the same. However, your caloric deficit of course would change (and you would need to lower it to match that to maintain your rate of weight loss).

In your hypothetical example, if your TDEE were 2000kCal and you were able to eat and absorb 4000kCal of butter a day, you would gain weight (although slower than the expected 0.57lb/day due to increased TDEE; this expenditure change (up to +50%!) was shown in the Vermont State Prison overfeeding experiments in the 60s). But despite that, due to the complete lack of carbohydrates, this diet would definitely stimulate ketogenesis (and would do so regardless if your TDEE were a 2000kCal surplus or deficit).

Due to the complete lack of proteins, you would eventually start consuming some lean body mass to produce some of the glucose (a percentage of glucose would be provided by the glycerol molecule holding together each triglyceride) required by the brain (~30%) and RBCs. I'd expect a pure butter diet to have about the same physiologic effect on protein-sparing as an extended fast (eg, you'd probably last a couple months before eventually expiring).

You can drink 4000 calories of ethanol and not gain weight though! It's the only macronutrient with no storage form. From this was derived the infamous lean chicken breast and tequila diet. Biologically impossible to gain fat on that diet. Dietary protein is used as such, very little is converted into glucose and of that virtually none becomes lipids[1].

Never said it's healthy, but you will lose fat. If you're not keen on the ethanol poisoning aspect of the diet, you can substitute complex fibrous carbs like broccoli or some such and get similar results.

Of course if you really don't care about health you could poison yourself with Dinitrophenol. It's the fat burning drug. Literally. Users routinely die from their bodies cooking them to death.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636601/

The people that die have an obsessive behavior (like anorexia or body image issues) that cause them to ignore the side effects.

If you were taking a drug and it made you feel horrible would you take more? Most likely you would stop or at least forego increasing the dosage.

These people didn't die because of dinitrophenol. They died because of an underlying condition. It's an accidental suicide.

While on the surface this may seem true, this is actually totally false. For example, if you eat too much protein in one meal (even with no carbs) it will still throw the body out of ketosis. The science of staying in keto is way more nuanced than "no carbs" (which is nutritionally impossible, anyway). Again, read the blog I linked to if you want to know more.

There's no best diet, there's just a diet that works for oneself. For me it's a ton of fruits (tomatoes, clementines, .. depending on the season), vegetables (onions with leaves, spinach leaves, herbs, peppers, aubergines, carrots...) vapor-cooked or boiled in water, occasionally with some white fish, and some rice to 'cement' a bit that, some honey. No sauce and no waste or almost, no drugs (this diet is like a natural drug for me). Doing some exercise the weekend on a bike. My BMI is always around 18 (60/1.83^2)

Agreed. I am in a much worse state than you. Diet of any kind at this point sadly won't help me any more. Now I have to trick my metabolism into using glucose very inefficiently.

Have you considered increasing your exposure to sunlight? It should help with the lowering of blood pressure through an increase in nitric oxide levels among other things.

Linking an article to with a brief overview, but there are many studies that can be found online.

[1] https://www.outsideonline.com/2380751/sunscreen-sun-exposure...

Congratulations on your progress!

Interested why you decided against metformin. Lots of people without DM or Metabolic syndrome are taking it for its apparent life extension effects (mostly unproven this far in humans). For diabetes, there's pretty solid evidence.

I work in this space tangentially and I had not heard of berberine before. What are you hoping to achieve with this supplement?

Berberine has been shown to be as effective as metformin at controlling blood sugar with additional anti-depressive benefits.

https://examine.com/supplements/berberine/

I don't think it's comparable. That link overstates the amount of evidence. Notably the only good trial didn't compare it to metformin. Three small trials and a meta analysis. There is decades of experience with and significant evidence for the efficacy of metformin.

Metformin is great if you like shitting your pants constantly. The life extension crowd is going to give us a lot of laughs.

Berberine can do that as well. You have to start off with small doses and let things adjust. I've been doing so many supplements for so long that it didn't really affect me much.

Congrats on your progress! I assume you still have metabolic syndrome (have you gotten your fasting insulin tested? What's a shame is most doctors test that, which is a $30 assay and the only way to calculate HOMA-IR or QUICKI IR estimates).

While I can't disagree w/ Metformin/Berberine being effective for glucose control, I personally don't think that they aren't great long term for the dysbiosis, B12-deficiency (for metformin) and toxicity (for Berberine) effects... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478780/

Most people that haven't long-term diabetic (eg, completely destroyed beta cells) should be able to get their health back in order via primarily dietary interventions, although it may require some detective work (conscientious dietary, blood work, body composition tracking).

Some of the hypertension may require addressing the IR, which can just take time to resolve: https://www.ncbi.nlm.nih.gov/m/pubmed/3299096/

Some of it may also be insuring adequate electrolytes, most people are much too low on ketogenic diets: https://blog.virtahealth.com/sodium-potassium-magnesium-keto...

I think waist:height ratio is definitely the best home measurement, but hopefully you're getting good supporting bloodwork as well, which can be very helpful in helping diagnosing problem areas. Also I found DXA and RER testing to be personally quite useful as well, especially for tracking progress on visceral fat (I took off 25% of my body weight off starting last summer). Good luck!

Congratulations! Keep going!

Adding 20-30mn HIIT sessions fasted right before breaking the fast may help also.

The hypertension may be related in some cases to sodium depletion causing aldosterone production (and cortisol and adrenaline) leading to fluid retention (and potassium excretion).

For this reason some people supplement themselves with sodium/potassium during keto or long term (72h optimally) water fasts.

Insulin resistance is related to inadequate protein, not excess fat per se. You may need more muscle, which is partly based on getting the right kind and amount of protein.

Egg whites are the most bioavailable protein. Humans can use about 98 percent of it. I used egg whites to good effect when one of my sons needed more protein for some reason.

Reference:

https://news.ycombinator.com/item?id=8748147

(This is not advice per se. I'm just making conversation and super tired.)

The positive association between egg consumption and prostate and colon cancer that has been showing up consistently in studies since the 90s is concerning. I'm not sure the risk is worth it.

I eat eggs every day. Also spinach, onions, garlic, broccoli, sometimes wheat grass juice. Most of my protein is low quality soy from adv formula slimfast and I know that isn't great. Whey protein disturbs a wound in my stomach which I am still waiting to have doctors look at.

Did you take in enough Electrolytes? Like Salt, Potassium and Magnesium? Because you lose a lot of Water and Minerals when doing this diet.

I also found that for some reason, MSM (Methylsulfonylmethane), caused me to lose several pounds of fat.

I don't exactly know why, but some suggest it reduces inflammation, or improves blood sugar regulation.

From wikipedia:

Multiple human and animal trials indicate MSM may reduce oxidative stress and inflammation.

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.

Did you notice any other effects from your fast?

I haven't had a full panel of biomarkers tested since the fast. I will post here when I do.

The only obvious changes have been 1. Smoother, younger looking skin with fewer blemishes 2. I look ripped

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?

https://chriskresser.com/when-your-normal-blood-sugar-isnt-n...

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...

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

How does one know if they are one of the 25% of Americans with "metabolic syndrome"?

Start by getting your A1C measured, which many/most doctors do as part of an annual checkup for adults.

Here you go: A comprehensive definition for metabolic syndrome https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675814/ - see Table 1 as the definition can vary, but NCEP ATP III is 3/5 of central obesity, fasting glucose (or high HbA1c), >150 mg/dl of TG, <40 mg/dl(M) <50 mg/dl(F) HDL, >130/85 mmHg blood pressure.

A recent review of 2009-2016 NHANES data concluded that only 12.2% of Americans were in "optimal cardiometabolic health". https://www.liebertpub.com/doi/10.1089/met.2018.0105

The guidelines they used were (very similar but slightly more stringent than the ATP III):

* waist circumference (WC <102/88 cm for men/women)

* glucose (fasting glucose <100 mg/dL and hemoglobin A1c <5.7%)

* blood pressure (systolic <120 and diastolic <80 mmHg)

* triglycerides (<150 mg/dL)

* high-density lipoprotein cholesterol (≥40/50 mg/dL for men/women)

* not taking any related medication

Even w/ ATP III, only 19.9% of American adults don't have metabolic syndrome.

What metabolic syndrome really is, is hyperinsulinemia/insulin resistance. You should get your estimates by having fasting glucose and fasting insulin tested for to get HOMA-IR and QUICKI estimates (TG-FB and TC/HDL are two other estimates you can use). If you are IR (probably 80% of American adults), then you can improve this by eating less often, eating earlier in the day, or eating less carbohydrates (especially those with a high glycemic load) - doing all three is pretty doable and actually tends to work synergistically (endocrinology!). Exercise also helps improve insulin sensitivity, but you can't really outrun a bad diet.

> >130/85 mmHg blood pressure

Praise the power to define/change definitions of these values...

There's a very inexpensive treatment for many people with MetS -- weight loss: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898932/

To piggy back another comment take a look at Jason Fung's clinical work with people with metabolic syndrome/Type 2 diabetes. It's focused on using fasts to so-to-speak "reset" a metabolism. https://idmprogram.com

https://m.youtube.com/channel/UC8bWMq7Ahg3CUz3ish9dvuw

keto does that, or even carnivore. Dave feldman does a ton of experiments on this

I had the same problem and then started Keto/IF and also switched to better Oils (less Omega6)for cooking and also eat a can of cod liver (packaged less than 6 months before) which has lots of Omega3 and Vitamin A every two weeks. I have the feeling that everyone is different and there isn't one solution that works for everyone. But sugar, processed foods, and too much Omega6 are a big factor in a lot of illnesses.

Vitamin D3 is said to help with metabolic syndrome. Also, intermittent fasting (eating within the same 8-hour window) and keto. Estrogen, DHEA, vitamin K2 MK-4, etc.

https://vitamindwiki.com/Overview+Metabolic+Syndrome+and+vit...

I take D3, K2 MK4, K2 MK7, chelated magnesium religiously. For some reason, DHEA doesn't agree with me. I get headaches from it. Excess D3 also causes pain in the back of my head and neck. Curious if its related to calcium scavenging or some deficiency.

How much DHEA did you take and was it with pregnenolone? 5 mg + 5 mg topically is said to be the preferred way to supplement.

The pain may be related to blood pressure.

Is there any reason you didn't also add a multivitamin? How much D and K? Magnesium? Ever had any lab work done?

I also use a multivitamin from time to time, but I get some crappy multivitamins from adv formula slimfast, rainbow-lite and both contain fake vitamins (like ascorbic acid). I try to get most of my vitamins from food.

My BP is under control though I would love to stop using BP drugs. In fact, I would like to see legislation around the use of them, i.e., doctors must within 180 days, find the root causes of the abnormal BP and within 360 days, have the person on a program to fix it. BP drugs are bad news and put people at grave risk (as the body fights the effect) which means if you stop taking them, your body fighting the ffect triggers a rebound. It's happened to me twice when the pharmacy was screwing around with my prescription.

Magnesium is 100mg, 3 times a day. It is chelated and bound to a couple amino acids. K2 MK4, 100mcg twice a day. K2 MK7 100mcg twice a day.

The only lab work I've had done was testing for the usual things, cholesterol, triglycerides, checking for h.pylori, etc... I don't think they even do a ldl lipoprotein spectrum graph.

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".

Lots of things that have upstream causes also have downstream effects.

Yes, but if you cure the "cause" then the symptoms go away too.

Well, sometimes, but sometimes it's like closing the barn door after the cattle have escaped--too late!

Eventually you will get the cattle back and it's best to have the door fixed when you do. If you don't the cattle will just run back out.

This article suggests that it might be the symptom of one disease while being the cause of another disease (or range of diseases).

For example the "fat cell leak": The body is correctly responding to a real problem, but the response is so heavy handed it causes other problems.

Which is why suppressing inflammation might be an interesting area of research, but we wouldn't want to completely eliminate it because the body may lose a vital tool needed to fight illnesses and normal maintenance.

That doesn't change the fact that the "cause" of the whole issue is not a symptom.

For example, you can get a blood infection from really bad gingivitis. But it's quite a leap to blame inflammation as the "cause" when it's really plaque (or a myriad of other related things). I think this is the foundational problem with health sciences.

There is a lot money to be made treating symptoms, very money little to be made curing people.

I think what the other poster is saying that the bi-products of the inflammation response in themselves can also cause a problem. Yes, the obesity is probably the "cause" in the first place, but telling a person to go on a weight loss diet is going to be a bit late if that's not going to save them before the inflammation kills them.

If you've got 2 or 3 different things killing you at once, you're gonna have to deal with the "most killing" one the most, so to speak.

While I don't disagree with the concept of prioritization, that's not the same as cause and effect.

Inflammation is an effect that _can_ cause other problems. But as far as I know, inflammation is a symptom of other problems, not a cause in and of itself.

Did you read the article?

The article claims that inflammation is both a symptom of other problems (when in reasonable ranges of signalling) and a causer of problems (when signalling too much).

I know the title of the article itself is a bit sensationalist, but I would assume that any tests aiming to determine if inflammation is the cause of a problem in specific would also check to make sure that the inflammation was in the "starting to cause harm" range rather than merely in the "signalling" range.

Of course a symptom can cause other problems, this has been addressed in multiple other comments. But suppressing a symptom (inflammation) does not remove the cause of the problem.

fyi:

>Please don't insinuate that someone hasn't read an article. "Did you even read the article? It mentions that" can be shortened to "The article mentions that."

https://news.ycombinator.com/newsguidelines.html

Your imunorespknse to a modern diet is one example of what triggers a cycle of inflammation. The diet isn’t necessarily good for you, but isn’t inherently bad. A 70,000 year old metabolism treats food the same way it did 70,000 years ago - turning much of the food into fat and surging you with insulin. This is what causes the inflammation. Your body isn’t in an era of scarcity - this response isn’t needed, nor is the subsequent inflammation

If the body's response to the current diet in the US (not necessarily in other countries) causes system wide inflammation, then the cause of the damage is diet/food, not inflammation. Inflammation is the symptom, regardless if there are cascading effects, they still start with the root cause.

AFAIK 40% of thin people also have health problems from the metabolic syndrome (e.g. CVD, diabetes), whereas 20% of the obese are healthy.

People focus too much on obesity, but obesity is more like a marker rather than a cause (even if it can make things worse by fat cells becoming inflammatory).

And I have to agree with the parent, we have an obsession with treating the symptoms instead of the cause. And there are cases in which treating those symptoms does not reduce the all cause mortality rate

The perfect example is statins. A high LDL-p might in fact be the body’s response to infection and by impairment of LDL particles production or by accelerating clearance, you can end up doing more harm than good, even if a high LDL-p is a good marker for CVD. And then you’ve got a ton of side effects that reduce quality of life, because such pills are a blunt tool with a lot of downstream effects, some of which are unforeseen.

And to put salt to injury there are studies showing that statins don’t reduce the all cause mortality in patients that haven’t suffered a stroke already. Or that even in patients that suffered a stroke, the life extension is measured on average in only a couple of months. Which actually makes a lot of sense if you really think about it.

Inflammation is tricky because you have accute (a hard work out, an injury, gingivitis) or chronic/dietary inflammation which is more akin to a reversible disease.

It’s like saying type2 diabeties or fatty liver disease are not diseases but symptoms caused by certain dietary habits. Though as I write this...maybe you are correct and we should look at these things like symptoms of poor diet and not diseases.

I think it's a hard problem, especially if you have to tell someone they have control over the cause. (certainly not always the case)

Recently a couple of friends had heart issues. One event went so far as the Mayo clinic and the doctors there said that she needed to stop eating white sugar (one issue at least) because it was scratching her arteries and causing inflammation.

Is inflammation really the problem she is having? She is overweight and didn't want to change her diet. All she heard was "inflammation is the problem", not "change your diet".

If one system's inflammation causes another system to degrade and inflame, and so on, until the body has systemic inflammation without an infection... that over-sensitivity/self-reinforcement mechanism is arguably the problem, but also a moot point without advanced gene editing. The "fix" may be reducing inflammation so those systems can recover homeostasis.

Sure, but if you cure the first problem, then the inflammation goes away, then you cure two problems instead of one. So is inflammation really the actual problem?

This is like saying water damaged my carpet without acknowledging the real problem... that firemen were putting out the fire. No one cares about a mold problem in carpet if your house burns down.

If we treated health issues in the same common sense way we would not focus on symptoms, but on causes.

I think it's analogous to overwhelming tech debt - stuck in an operational hell because there is no reprieve to actually put out any of the fires.

The root cause is all the little issues, but you can't get there without first tackling the inability to fix any of the issues (labor shortage/unreasonable expectations/so on).

Inflammation is not just a symptom, but also an underlying process.

Lots of things can cause inflammation, but the underlying process can be similar. And it can have good and bad effects.

Can you provide an example where inflammation _is_ the problem and isn't a symptom caused by something else (ie, disease, damage, toxicity, etc...)?

Immune disorders like MS. The immune system attacks the persons own tissues. It’s the inflammation that causes the damage. Prevent inflammation and you stop the disease.

It seems that a faulty immune system is the cause in MS, and inflammation is the symptom... can you clarify your example?

Sure, the immune system is at fault, but it’s the inflammation that causes the damage. Since we don’t have great tools to tweak the immune system, if we prevent inflammation, we can stop the disease.

It seems illogical to attempt to redefine inflammation from a symptom to a cause because of the inability to cure the known cause.

Suppressing inflammation is still temporary relief, not a cure for the root cause.

I don't get why you're so resistant to the idea that sytstemic inflammation (not gingivitis) can simultaneously be a symptom of one condition and the primary causal factor in many others. The article gives plenty of examples of conditions where inflammation does seem to be the root cause. It feels like you haven't read it, in which case I highly recommend doing so. It's quite educational and not not at all biased towards a big-pharma solution.

The article also gives sound reasoning for why metabolic stress, i.e., overeating, eating crap and not exercising, could be the most common cause of chronic inflammation. I would guess that psychological stress is another big factor given it's known ability to exacerbate autoimmune and inflammatory conditions. So the cure for most cases of chronic inflammation is going to be the usual mix of diet, exercise, sleep and stress management. We already know that these are the most effective preventative measures against age-related diseases and this research gives us a better understanding of the underlying mechanics.

Just FYI, suggesting that someone hasn't read the article is against the guidelines.

So, what I think is happening is that excess acidity (and other chemical derangement) causes inflammation which promotes infection which causes more inflammation. It's a vicious cycle with a positive feedback loop.

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-...

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

I'm sure I remember reading an article on HN linking gum disease to alzheimer's...

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.

> inflammation is the description of what is happening (ie, symptom) not the "cause"

If you chemically turn off inflammation and the negative downstream effects disappear, then inflammation is arguably a cause of those negative effects. Inflammation is supposed to be a healthy response to various conditions, but that isn't always the case, so when it's causing negative effects it becomes a pathology and arguably a cause.

Now if you're trying to argue some sort of infinite regress, then the Big Bang tautologically caused everything and nothing else is a meaningful cause.

The term "root cause" was not invented for nothing. One should always try to find the root cause since if you do not find it you are fighting a symptom instead of a cause. There is a huge amount of research about what causes inflammation so it is correct to say that inflammation is a symptom not a cause.

> There is a huge amount of research about what causes inflammation so it is correct to say that inflammation is a symptom not a cause.

It is not necessarily just a symptom, that's the point. So no, it's not necessarily correct because sometimes inflammation is exactly the cause.

I think because a symptom can be part of a cascade of problems doesn't mean we should ignore or dismiss the root cause as the most important thing. As far as I know suppressing inflammation is a temporary stop-gap, not a cure.

Can you demonstrate where inflammation does not have a root cause?

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.

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.

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

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/22381097

same for NSAIDS (ibuprofen etc) and bone healing

They told my wife to only use Tylenol(acetaminophen, which isn't an NSAID)for pain when she broke her back. Inflammation has important uses, but like auto-immune disorders, too much can cause other problems.

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.

I can’t find the citation right now, but as I recall, a lot of connective tissue has very little blood flow. Inflammation increases blood flow, which can help with healing.

Achilles tendinosis is a good example of this. The achilles tendon replaces cells at a very slow rate. If there is chronic damage, it can take decades to heal on its own. But if you intentionally damage the area with eccentric heel drops, it can heal fairly quickly.

Doing a similar protocol with my patella tendon

Similar experience here. I had residual pain from a neck fusion and doc put me on those 800mg ibuprofen horse pills + PT. It seemed to help at first but then plateaued and didn't seem to help much. After I had been on ibuprofen for months I noticed that small cuts on my hands (typical for my line of work) were slow to heal.

One day I went to a lecture on brain research by some top neurologist at Stanford. As an aside about the difficulty of maintaining double-blind standard in actual experiments, she mentioned that she once worked on research involving NSAIDs. To mark the mice for tracking they punched coded holes in their ears but found they could tell which mice were getting NSAIDs because the holes would not heal for the treated mice whereas in untreated mice the holes would heal. I tossed the horse pills that night when I got back from the lecture and the cuts on my hands started healing normally again.

I've read that taking NSAIDs for exercise-induced muscle soreness is counterproductive, as they can inhibit new muscle growth. Seems like this could be related.

Anecdotally, my own experience with chronic back issues is the reverse, and jives with the explanation I was given. My lowest 3 disks are degenerating, with the bottom disk almost gone. About 8 years ago I had to have a laminectomy due to a disk bulge pushing against a nerve, and no amount of NSAIDs nor physical therapy would fix it.

I had herniated disks before and after, but only one required surgery. For as long as I can remember, I'll get severe back pain once or twice a year, which eventually goes away. The explanation I received for these events is that it is likely that the outer sheath of a disk is getting torn, stretched, or some other type of trauma. This hurts in and of itself, however, additionally the disk material may begin to bulge. Once bulging, that part of the disk loses access to nutrients and moisture and eventually dries up, with the bulge receding and the damage scarring over. The doctor described this like a grape to a raisin, though I'm sure it looks nothing like the analogy.

Summary, with time, the disk sheathing trauma scars and the bulge dessicates, possibly about the same time NSAIDs are declared of no help.

For me, I definitely notice much less pressure in my back when on an NSAID, and I sleep much better as well.

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.

Isn't this the concept behind dry needling?

I do believe so.

Ibuprofen interferes with absorption of one of the B vitamins. Long term use promotes a B vitamin deficiency.

I had something similar, woke up one morning and had this crazy pain in my upper spine which went into my right arm.

The pain was so insane nothing helped (didn't try oxy though). I went to a million different doctors of all types and nothing really helped.

It wasn't until a met a chiropractor who told me that it was some upper disc fracture which resulted in some liquid pushing on my nerve and that the only thing I could do was to make some neck exercise to pump blood through the area which would make it heal.

That helped within 3 weeks.

Yup, and anti-oxidants actually prevent aerobic conditioning in athletes.[1]. Presumably oxidative stress is a signal to the body to become more aerobically efficient.

Yet at the same time, oxidative stress is linked to numerous diseases.

Biology is hard.

[1] Derek Lowe’s blog (don’t have exact link)

It's almost as-if our cells depend on some sort of chemical equilibrium. The old advice of everything in moderation may be the best way to go.

"Biology is hard" doesn't really express what I think people don't get about biology (granted I'm not a biologist).

With everything complex, not just living creatures, the real problems are caused by failure to maintain a negative feedback loop properly, and pushing on it doesn't help because the negative feedback is still there almost the same way as normal and has to be to avert complete disaster.

I'm not sure your explanation was any easier to grok for people, how about this:

Inflammation is what the body uses to clean out disease and heal itself.

The individual mechanisms used to do this could be considered analogous (but very different from) a short antibiotics regimen.

In the short term or localised to one area it is beneficial. But at a systemic always on level there are negative side effects where these systems begin to overwhelm/damage healthy functions/cells.

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

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

Yeah but who's going to do that?

No, the article isn't about this drug at all. It gets mentioned at the beginning, mostly. The rest talks about biology. The main takewaways for me, after having read it in its entirety, were:

  * exercise regularly
  * don't overeat
  * ensure you're getting enough omega-3 (EDA and DHA,
    from fish/fish oil/algae) and arachidonic acid 
    (beef/chicken/eggs)

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

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

Why scientific "consensus" is not scientific.

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?

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

Except major performance decrease. Some people cannot afford that.

No. Reduce refined sugars and habit of fasting becomes like second nature.

Beginners can start with just intermittent fasting.

If this not affordable, then have to afford a more costly one - chronic diseases.

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

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.

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.

Very interesting. I remember reading that traffic accident rates go up significantly in Muslim majority countries during the first few days of Ramadan (daylight fasting), so there appears to be an adaptation period with decreased performance before the benefits kick in.

When following an intermittent fasting protocol (eating within the same 8 hour window, for example), productivity tends to increase in the fasted state. Maybe there's some initial adjustment period.

"Except major performance decrease. Some people cannot afford that."

This was my first reservation about fasting and while everybody is different and you'll need to see how your own body responds, I am happy to report that the following activities:

- mid to long distance runs (4-8 miles) - 60-90 minute power movement weightlifting session - routine crossfit workout and/or plyometrics - BJJ class with 5 minute sparring rounds

... are not only not impacted, but are in many cases enhanced by being in a fasted state. The most positive impact is in my weightlifting workout[1] which, ironically, is the activity I thought would be most negatively impacted.

I can't speak to 50 mile ultra runs and I know I can't do all of the above in a fasted state - but I never attempted to do all of the above on the same day anyway.

Just try it.

[1] Power movements, relatively heavy weights and relatively low reps. Just the kind of workout you'd think would be difficult while in a fasted state.

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

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.

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

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/

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.

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.

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

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.

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.

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. 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.

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...

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

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

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.

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

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

Unexplained inflammation might be sign of an undiagnosed condition.

What causes inflammation?

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

Name them.

Here's one, grandfathered in 1958...

https://en.wikipedia.org/wiki/Sorbic_acid

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

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

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.

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

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

Perhaps, but Inflammation is detected via several blood tests e.g. CRP which presumably can't be imaginary and signify some real physical processes.

https://www.ncbi.nlm.nih.gov/m/pubmed/15823493/

> 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?

"Why not work on becoming smart than telling people to eat pills?"

Because that has worked about as well as the war on drugs for the past 30 years.

Your quote says "humans are hard-wired to conserve energy", not "humans are soft-wired to be stupid and can learn to be smart".

Where does "work on becoming smart" address anything you quoted?

The quote is assuming people are "machines" hard-wired to eat bad food and don't work out. I deeply believe humans are smart and can reflect and change their behavior. At least, we need to give them the chance to.

Where do you think did I not address the things I quoted?

Where do you think did I not address the things I quoted?

Quote: "People know what they need to do" - your response to that: ignore it, don't address it.

Quote: "that knowledge doesn’t change behavior" - your response to that: ignore knowledge entirely, state that "smarts" changes behaviour.

Quote: "Humans are hard-wired to conserve energy (citation)" - your response to that: don't address it, implicitly dismiss it, state that willpower overcomes hardware (no citation).

Quote: "prefer foods that are fatty, salty, and sugary." - your response: ignore it.

Quote: "This suggests that pharmaceutical interventions that block inflammation may be necessary" - your response: "really?" doesn't particularly address it. Yes, apparently, really.

Quote: "to check the global epidemic of non-communicable disease", your response to global epidemic of disease: "why don't people WORK HARD to be SMARTER, they're ill because they're dumb", i.e. dismiss it as trivial and uninteresting with a throwaway intelligence worship quip.

Hard-Wiring implies software can't change it. This is the fundamental point, if you're to address the things you quoted, you need to address why you think it's not hard-wired in the face of a claim that it is, or why the claim is unsupported. The world's population has become more overweight and obese over the past hundred years - is your explanation that it has become dumber since stopping working to be smart?

If you addressed the things you'd quoted, your comment would have included things like: why you don't think people "know what they should do", why you think people are not hard wired to conserve energy, why you think taste for high energy food is learned or is changeable and not innate, why you think "work to be smart" is a plausible way to address a global disease epidemic and what you think that work would involve, and how it could be taught to the world. Why you think it's possible that work can improve "smart"ness, is there anything to suggest that's true? AND/OR why those claims shouldn't be accepted.

Instead, "nah bro, just work at being smart" is the same quality of reply as "global disease epidemic of cancer may need chemotherapy" "really? why not work on raising your astral frequencies?". It's a feel-good non-solution that doesn't relate to what was said.

So, you are implying these are my responses even though I never actually wrote them? How is that different from telling me I did not supply citations?

You asked me where I think you didn't address certain points. As you didn't address them, I have no text from you to copy or refer to, I can only point around the area where you didn't talk, to show that it exists.

When you say "work to get smarter instead", that says the problem is a lack of work and a lack of "smart", and therefore that people are ill because they're dumb. It follows from what you said, even though you did not write those words out. So yes, I imply that your responses are your responses.

How is that different from telling me I did not supply citations?

I don't want to read citations, I mentioned them as one example of what "addressing a point" could look like, so that the absence of any of these possible things supports that you didn't address them.

I asked questions. I never thought about supplying citations when asking questions. I get the feeling you read lots of judgement into my question. My intention was to create a discussion around the question.

Anyway, I guess there is little value in discussing further. Thank you for explaining your reaction. Definitely food for thought

> 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.”

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.

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