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Inflammation: Medicine's burning question (newyorker.com)
141 points by matco11 on Dec 15, 2015 | hide | past | favorite | 152 comments

It's great to read things like this... I wish my GP would do the same.

I recently had a really high cholesterol reading (both total cholesterol and LDL). Everything else (blood pressure, blood glucose etc) seems fine. I'm 38, fit and healthy and nothing that suspect in my family history. I found the attitude of my doctor in all this quite surprising. It amounted basically to "You definitely have familial hypercholesterolemia. There is no other possible option here other than statins". No further questions about what I eat, my stress levels, lifestyle - nothing.

What disappoints me the most here is now that I feel like it's all on me to determine what my real risk levels are and what's appropriate to treat this. I don't subscribe to the mainstream NHS view still heavily pushed that eating saturated fat -> high cholesterol == unhealthy as I think it's a lot more complicated (as this article shows). I don't like being is this situation as I'm as susceptible to human bias as the next person, and I'm not a doctor, however almost all of the high quality, science based writing I've read indicates that the mainstream healthcare system's view on cholesterol is wrong.

> What disappoints me the most here is now that I feel like it's all on me to determine what my real risk levels are and what's appropriate to treat this.

A convoluted set of circumstances led me to a quick detour in grad school, to sit in on Anatomy at Harvard Med. This included the dissection portion, in which four med students hunch over the cadaver for 3-4 hours at a time. It lead to some of the best medical conversation I've had in my life.

The best topic was summarized as: When you visit a doctor, odds are that he/she has about 15 minutes to an hour to evaluate you before moving onto the next case (often because there are bills to pay.) If you are not an expert on your particular medical history and circumstances, then you are basically screwed, because there is nobody human who can digest all of your medical history and circumstances in the allotted amount of time. It still essentially holds true if you have some serious condition: Consider all of the other patients on the doctor's plate.

That, combined with several other stories and experiences, had a big effect on me: It became obvious that it is worth enormous amounts of time and money to keep fit. When it comes to the med community, the only way to win is not to play.

I had an issue a few years ago.

I was having frequent acid reflux and 2-3 nights a week, I'd wake up choking on it. This lead to issues with difficulty breathing and shortness of breath.

My doctor treated me with an inhaled steroid for the breathing difficulty and a PPI for the reflux. This helped but it didn't fix the problem. I'd wake up choking once every couple of weeks and this was not acceptable to me.

I started googling for my symptoms and I found someone who had a stomach infection that was causing his reflux, when he treated that infection, the reflux stopped.

I tried to get my doctor to run tests and he wouldn't. I went to a gastroenterologist and began asking him to test me for infections. He stated that the only possible thing that could survive in the acidic environment of my stomach was H. Pylori and since a gastroscopy didn't find any evidence of ulcers, I couldn't possibly have an H. Pylori infection.

I was insistent that I be tested for it... Two days later, I got a call that I did have an H. Pylori infection and the doctor would call in a prescription.

I took a ten day course of antibiotics and a PPI. Almost miraculously, I was cured. No more stomach discomfort. Almost no night time reflux. I wake up choking maybe once in 6-8 months. I am breathing better. I was damaging my lungs for years and it's taking time to recover from that damage but things are constantly improving.

Basically, I would be in much worse health if I hadn't sought out the experiences of other people and if I hadn't pushed back against the advice of my doctors.

You still probably have sleep apnea if you are ever waking up fully without the ability breathe. The human mind can wake up from deep sleep to stage 1 sleep in order to breathe better dozens of times an hour without you perceiving a thing. It only wakes up all the way when it's really bad. In fact, the acid reflux is often a symptom of sleep apnea, attempted inspiration with a sealed off airway literally sucks acid out of your stomach. Get yourself a sleep study. If I'm right, get new doctors and dentists, they all should have caught it by now. Good luck.

You are correct. I do have sleep apnea. I have been postponing it for a while but I do need to have a sleep study.

Agree 100%. The corollary is that, if you must play, make sure that you yourself are the best expert of your medical history, symptomology, and candidate hypotheses about what may be going on with your health. This is difficult, and perhaps futile, but the sad truth is that due to time issues (and probably information overload) it's your job to a) bootstrap the MD with whatever is relevant about your condition, and b) sanity-check the MD's decisions.

Failure to do either of those things is likely to result in either suboptimal care in the best case, actively misleading care in the worst. I guess the silver lining is that Google + intelligent and motivated person >= most MD diagnoses in my experience.

One resource I would add to your list: http://www.uptodate.com/

Since few MDs can actually stay on top of the latest developments for all the different items that cross their desks, UpToDate serves as a curated summary of many medical conditions, and is updated every 6 months (? maybe 9, it's been a while) for each topic.

It is a subscription service, and if you are dealing with anything in between problematic-to-serious, it is well worth subscribing for a month. If the language is difficult in whatever article seems relevant to you, it is worth figuring out the language because it will provide a good jumping-off point to go examine the literature on which it is based (which is likely your next stop, for serious conditions.)

I second this. In fact, the big secret is that all doctors use this as reference these days in clinical practice settings, while in the backroom on a computer. It is literally the doctor's goto wikipedia.

Great resource that I never would have known to look for. Thanks!

The NICE evidence, which your NHS GP should be following, is here: http://www.nice.org.uk/guidance/cg181/evidence

The NICE guidance, which your NHS GP should be following, is here: http://www.nice.org.uk/guidance/cg181

Your GP should have used more information than just your non-HDL results; they should have given you a standardised risk assessment call QRISK2.


That risk assessment needs to know your age, sex, BMI, ethnicity, family history, your blood pressure, your blood cholesterol levels, and whether you have history of diabetes, high blood pressure, atrial fibrillation, or rheumatoid arthritis.

Your GP should have most of that, and if you think they don't it's probably a good idea to let them know.

You've said that you think the "eating saturated fat leads to high blood cholesterol" thing is wrong, and that the NHS seems to push this, but you also say that your GP didn't ask you what you eat, so it seems your GP isn't pushing that hypothesis. Your GP (from what you've said) didn't say "stop eating animal fat and take this medication", your GP said "take this medication".

Thank you for those links!

I should have been clearer: what bugged me about my interaction with the GP was that he didn't ask about anything to do with lifestyle/diet. When I went looking on my own - everything I seemed to find from the NHS/Heart UK suggested that cutting saturated fat was essential, leading to my conclusion that this is what the mainstream medical establishment still believes.

As somebody in the same situation (same age, otherwise healthy, high cholesterol, regular exercise) my read is that trying to influence ldl in a meaningful way through diet alone is essentially pointless.

You can knock off a few points, and you can raise HDL a bit, but the likelihood of a dramatic reduction is essentially nil. Going right for the statins kind of makes sense beyond a certain point.

That said, I opted out. My gp showed me the risk in the calculator mentioned above and the difference statins made was not large enough for me to justify it.

If your triglyceride levels are too high you're eating too many carbs and not enough fish. If they're not, there is not as much evidence you really have a problem.

Could you define "dramatic reduction"?

Based on information I found using clinical resources which I have access to via my employer (I work at a University with a medical school and have access to their tools, although I am not a medical professional) I found this useful note:

> The United Kingdom Lipid Clinics Programme study of 2508 subjects found that, with diet alone, 60 percent of subjects had a mean reduction in body weight of 1.8 percent, which was associated with 5 to 7 percent reductions in serum total and LDL-C.

Key thing here: when I mentioned "otherwise healthy" above that includes "not overweight and exercises." Lifestyle interventions for people with hypercholesterolemia are most effective on people who are both sedentary and overweight (or obese) who have really poor diets. None of that applies to me.

The conclusion that I ultimately came to is that, if your diet isn't awful, your BMI is normal, and you exercise every now and then, there's no dietary change that's likely to benefit by more than 5%, not enough in my case to reach normal levels. This is my "gut" assessment based on personal research and I urge you to do your own research on this matter before making any decisions.

To further complicate all of this and bring things back to the topic of this article: statins seem to reduce the risk of CVD through some means other than simply lowering cholesterol levels. There's a school of thought that even people with normal cholesterol who have other risk factors for CVD should be on statins.

So really, the question of "should I take statins" may end up being less about cholesterol specifically, and more about overall risk of CVD. This is why in my own decision making process I opted not to pursue treatment (yet) since my overall health otherwise is sound.

Having skimmed over, one indication that my GP isn't up to date is that the lipid test is no longer required to be a fasted test, whereas mine was. Interestingly the specialist lipid clinic has also asked for a fasting test.

I'm coming from the US, but the tests that are run by a doctor are often constrained by what the nearby laboratories offer. New, validated tests may be delayed until the relevant laboratories deem them to be cost-effective.

Unfortunately, join the club.

I was diagnosed with type 2 diabetes. My initial fasting glucose was 161 and a1c was 7.1 . Not prediabates, but full on type 2.

So what does the GP say? "Here's some metformin. Oh look, high blood pressure. Here's some statins."

So, what do I do? Certainly not the doctor's advice. He didn't even give me the correct blood-sugar level in which damage is known to be caused (neurons die at 140mg/dL, no ifs ands or buts). Doc said 150mg/dL.

I've posted recently in what I'm doing, but esentially comes down to diet. Turns out that net carbs (or total carbs-fiber) is what causes my body to go haywire. Cutting down to about 10-20g carbs has done well for me.

Since doing only pure diet, 6 days is what it took for my body to start to noticeably fix itself. Now, my blood sugar doesn't go over 120, and my wake-up (fasting) glucose has tested at 100 the last 2 days.

Look up "Eating to the meter". If you can't measure, you can't reliably react and project. It's what I'm doing, and it's working. I have my data to prove it.

Thanks for sharing. I've taken a similar approach: cut all crap out of my diet and now in ketosis (according to urine strips). Ultimately this might not be the fix for me, and I might have to add some other interventions (like replacing saturated fat with polyunsaturated fat if I turn out to metabolize SFA poorly) but I'm also convinced that the primary fix must be dietary/lifestyle with some limited support from medication if necessary.

> if I turn out to metabolize SFA poorly

Is that a thing? Humans metabolizing Saturated Fats badly? I mean, I know of gall-bladder deterioration after maybe years of very-low-fat eating, but other than that. Would these people also weirdly burn their own body fat (saturated) "badly"? ;)

It would seem so:


I think that's essentially what a diagnosis of familial hypercholesterolemia means.

Likewise people seem to vary widely in their ability to handle high carb diets. I guess a cookie cutter approach doesn't really work across the board.

Cholesterol worries or issues in a lab panel may be troublesome, but the actual-process of fat metabolization (or any of the stages digestion, absorption, circulation, utilization, storage, burning, recycling) being "bad" compared to others/most I still haven't specifically seen mentioned including in the above.

High carb diets of course that's common. But saturated fat, you know, it's simply what fueled the ice ages!

It's curious you don't find this author biased.

That's an interesting statement considering you like to use links from nutritionfacts.org, written and run by a questionable [1][2] indivdual, Michael Gregor with an obvious bias towards vegetarian/vegan diets.


[2] http://www.humanewatch.org/hsus_doc_exposed_as_schlock/

I don't find him biased because he's balanced, when he doesn't know he says so and he backs up everything he says with rigorous literature. Peter is also the president of NUSI (http://nusi.org/solving-the-problem/), and as such dedicated to objective dietary science. In addition he's well respected by others whose work I also admire.

I'm an M.D. and let me first say this is not medical advice :). I long ago called bunk on the mainstream view on cholesterol and cholesterol lowering drugs. I think there will be a time in the future when doctors look back on it with a "what the heck were we thinking" kind of retrospective smugness.

That stated, familial hypercholesterolemia is a different thing and it's no joke. It's been a long time since med school but I think in this case the cholesterol gets high enough that it actually is a plumbing problem. That is your arteries will get gummed up with all that extra cholesterol.

By all means do your research but don't let denial prevent you from treating this properly. Listen to your doc or get a second opinion

Thank you for your perspective. I am very wary of treading the "mainstream medicine doesn't know shit and drugs are bad" path, and for that reason I very much appreciate a contrary view. My plan is to give it a few months and see if fixing some of my sub optimal lifestyle makes a difference or not.

I figure if I fix my sleep, cut the sugar and other crap and if necessary change my SFA to PUFA ratio and it doesn't get much better in 6 months then I'll have to take the pills. But I owe it to myself to try first.

How is you tryglyceride levels? That should be easy to change with just a diet alone. I believe it is due to consuming excess calories than you really need.

Trigs were fine. Overconsumption is certainly one more thing for me to look at.

Broda Barnes book [1] says, iirc, that high cholesterol levels are basically diagnostic of hypothyroidism. Usually people's superficial thyroid lab #'s look fine (TSH), but their body is not properly activating T4 -> T3.

[1] https://books.google.com/books?id=TJXf2ZqoxUIC

Yes, when I demured on the statin it occurred to my doc to check thyroid function (seems the wrong way round to me). My levels were fine.

Define "fine"... reference levels of TSH for example are controversial [0]. The HUNT study in Norway (which followed 25,000 healthy Norwegians for 8 years) found death rates 69% higher amongst women with TSH 2.5-3.5 mIU/L than amongst those with TSH 0.5-1.4 mIU/L [1] (via [2]).

[0] http://tpauk.com/main/the-tsh-reference-range-wars/

[1] http://www.ncbi.nlm.nih.gov/pubmed/18443261?dopt=AbstractPlu...

[2] http://perfecthealthdiet.com/2010/07/thyroid-more-evidence-t...

Are there some tests we can do to identify this issue?

Fair enough

I recently visited my GP and I had a high cholesterol reading. He suggested me to reduce sugars and white flours, get a reading in a month, and depending on that he'll decide whether to prescribe statins.

It surprised me that he didn't mention reducing saturated fats or meat consumption. It made me wonder whether refined carbohydrates play a role in high cholesterol. I think I'll have to take a look at the research.

I've collected a lot of research on low-carb diets. In my previous job as a neurology professor, I had access to all of the most medical journals, and was able to save a lot. I have been on a ketogenic diet for 2 years now, and my LDL cholesterol went from 180 to 130, my HDL from 28 to 80, and my triglycerides from 140 to 75. Plus, I lost 70 pounds, no migraines for 2 years, and my anxiety and depression have all but disappeared. 75% of my calories are from fat (50/50 saturated/unsaturated, mostly from red meat, oils including coconut, olive, and avacodo, butter, plus a TON of vegetables). This is pretty typical.


On page 29, there is a cool paper showing ultrasound cross-sections of blood vessels before and after a low-carb diet, and the resulting dramatic decrease in inflammation.

That's great! I've saved the document.

Seeing now that you were a neurology prof, I have a question.

About 10 years ago I followed a diet similar to the [Slow Carb Diet](https://en.wikipedia.org/wiki/Slow-Carb_Diet) in order to lose fat slowly over a long period of time. One of the unexpected side effects was that I felt extremely clear-headed. I was doing software development at the time and I remember being able to breeze through some thinking tasks. Years later, I was feeling foggy so I used Modafinil and it gave me a similar effect. The low-carb acted as a nootropic on me.

Is there any mechanism that you know about that could make this possible?

Or was it all on my head?

I believe it completely. This was one of the first effects I felt, before I had gotten deep into the literature. I remember after being on keto for a week, I was walking through a parking lot, and all of a sudden it was like my head popped through the clouds. I had a sudden burst of energy, my anxiety dropped, and I felt like skipping to the car. The keto flu disappeared, and I felt HAPPY for the first time in years. All in the course of 5 minutes. Over the next few weeks, I realized this had extended to my work as well: I felt focused, clear-headed, and able to work more quickly than I had in years. I used to get 1-2 migraines per month. I haven't had one in two years. I started the diet for weight loss (70 lbs now), unaware of the other benefits. It turns out this is starting to be supported by literature, though it is still a new area of study.

I started this because of my work in the pediatric epilepsy department I worked in. Nearly all of the kids that came through were put on a very low carb diet; it significantly reduced or eliminated the seizures in about 60%+ of the cases. Naturally, I wondered what was going on. It turns out that there are a number of neurological benefits. It has been shown to treat bipolar disorder [1], schizophrenia[2,3], ADHD[4], and so on. A lot of these are small studies. I am fine with that. If you have a patient who has been schizophrenic for 50 years, and no medication has worked, then a dietary change reverses most symptoms in a week, I feel comfortable saying something significant is happening, even with N=1. (A few years back at a Society for Neuroscience meeting, some NIH director made the point that if I say I have engineered a flying pig with wings, and bring it out on stage as proof, it doesn't make sense to say repeat it 10 or 100 times; the proof is sitting in front of you!). I have only cheated twice in two years, and both times I was groggy for days, and felt the depression creeping back. I realized this was how I ALWAYS felt previously.

[1]http://www.ncbi.nlm.nih.gov/pubmed/11918434 [2]http://www.ncbi.nlm.nih.gov/pubmed/26547882 [3]http://www.ncbi.nlm.nih.gov/pubmed/19245705 [4]http://pediatrics.aappublications.org/content/129/2/330

Please see the PDF document on http://www.atkinsexposed.org/ and let me know how it relates to your research.

I'd give Peter Attia a look: http://eatingacademy.com/start-here

His writing is incredibly in depth, and he's covered cholesterol extensively.

Also be sure to see the following very critical review of this person begging us for money - http://plantpositive.com/a-very-serious-low-carber-nusi/

> No further questions about what I eat, my stress levels, lifestyle - nothing.

A friend has familial hypercholesterolemia - cholesterol levels were around 1000 as a child, on statins since like, age 10.

At their request, the doctor dialed back the statin dose and cholesterol levels shot back up within days - even on a vegetarian diet with plenty of exercise.

They asked if they could start eating egg yolks again and the doctor said something like, "Go ahead. Your diet does not affect this condition at all."

Familial hypercholesterolemia isn't the same thing as having a 300 cholesterol level because you eat McDonald's. Listen to your doctor - they do know some things.

Absolutely, agree with all of that. What I'm moaning about is the absence of desire to explore further. I don't know if I've had high cholesterol for a long time or not or whether it's lifestyle or not, or whether I do actually have a 1 in 500 genetic mutation that means that my liver doesn't process cholesterol correctly or not. I want to look into some of those possibilities a bit more before I take drugs for the rest of my life is all :-)

The thing is, if you have familial hypercholesterolemia, some forms have life expectancy of 35 without medications. Patients might have severe atherosclerosis at the age of 10. There is a seriously heightened risk of CVD mortality without statins no matter what you eat or how hard you exercise if you really have it. So in that case your doctor is correct: there's nothing you can do but take medication. But what were your lab results for LDL?

Yeah, I'm aware of this and it's pretty scary! That's why I'm certainly not ruling out the drugs. What I want to do it figure out if I do have any damage with a CIMT test. If that shows I'm taking damage then it's a done deal, but If I can change my LDL through diet I think I owe myself a couple of months at least to try.

I'm not that familiar with the CIMT test, but by quick glance it only tells whether your carotid artery is affected. A negative result won't tell you whether the rest of your arteries - such as the coronary arteries - are affected.

But I'm a bit curious: Who referred you to a test like this in your condition?

Nobody did, I just phoned my GP and asked him if he could, but he said that's a question I'd have to put to the specialist. My reasoning was that I want to assess whether I already have arterial damage or not, as that will have a significant bearing on how I asses my risk of not taking statins.

Regarding your earlier question, my LDL was 7.8 mmol/l and total serum cholesterol was 10.3 mmol/L (I make that and 301 and 398 in US money)

About assessing the risk of not taking statins: As I said, the exam you're about to take is only able to give you positive answer (yes, your carotid is sclerotic), not negative (won't say: no, your coronaries or the rest of your arteries are not sclerotic), so it's sort of useless.

What I'm still wondering is how a familial hypercholesterolemy would have been missed during earlier blood tests? It's a pretty standard test here, and 7.8 and 10.3 are extremely high for a fit person.

Interesting point on the CIMT test, I hadn't considered that. I'm not sure I've ever had a cholesterol test before, so that might be why it wasn't picked up. :-)

My GP seems to be saying the because I'm fit and healthy, there's no other possible diagnosis than FH given the high numbers. I was kind of hoping for a bit more investigation and perhaps some corroboration. I'm not sure what form that should take though - genetic screen perhaps?

Probably there is no other possible diagnosis if your thyroid is ok. You can go do tests, but also the treatment probably remains the same (statins, etc.).

> some forms have life expectancy of 35 without medications

This. You don't have a lot of time to experiment.

My guess is it's best to listen to your doctor and get on statins immediately. Then alter your diet and activity level, and after that try cranking back the statin to see if the lifestyle changes took.

Lifestyle or dietary changes don't work if he has familial hypercholesterolemia. You're not supposed to ever adjust your medication without consulting your MD. It's a good general rule that - when broken - can have fatal consequences in serious diseases such as this.

I agree with you - we're just getting our signals crossed.

My unspoken advice was, "under doctor supervision," which I assume everyone understands (I know, a lot people don't.)

You can get a genetic test for FH, but afaik they're rarely performed, although maybe the OP needs one to convince them they really have the condition.

What I suggested was to follow the doctor's advice and, later, under their supervision, adjust statin dosage after lifestyle changes to see if the condition is still present. I'm not a doctor, but I know that my friend's doctor did exactly this - not as a way to convince them they had FH (they were already convinced), but to see if they needed that high of a statin dosage (they did.) That may be what the OP needs to be convinced, while also staying safe.

We both agree that the OP needs to be convinced that they have FH as soon as possible, and should do nothing regarding their treatment without a doctor's approval.

> almost all of the high quality, science based writing I've read indicates that the mainstream healthcare system's view on cholesterol is wrong.

My understanding is that a doctor's first job is to be risk averse. That's why they shy away from bleeding edge research and knowledge, and choose instead to rely on proven ways.

Their job isn't so much to be right as it is to not be wrong. If that means keeping you suboptimally alive, but still healthy, then so be it. Better than try to optimize and risk worsening your state.

The problem is, there is no research stating that lowering dietary cholesterol leads to lowered blood levels and the reversal of fatty liver disease.

There is research stating that fatty liver disease exists due to long term over-production of cholesterol in the liver, caused by low dietary cholesterol, and increasing dietary cholesterol can lead to the reversal of fatty liver disease; and such research isn't really cutting edge, much of it is around a decade old now.

The FDA has reversed course on this, and is no longer hammering its anti-cholesterol drum.

> much of it is around a decade old now

Has your doctor done any research/training about cholesterol in the last 10 years?

I'm being snarky. But I think it's important to consider the lifecycle of doctor careers. If you go to a liver or cholesterol specialist, then I'm sure they will be up to date with even findings from the last year. But I wouldn't expect a GP to be up to date on what every field within medicine has decided in the last decade after years and years of back-and-forth.

It's almost like asking a computer scientist to know both the difference between Angular and React, and how to rewrite COBOL mainframe code into Lisp. The actual job of a computer scientist is writing proofs in Coq and understanding the difference between lexical and context-free grammars.

You have a misinformed view of what a "computer scientist" is; I have never written a Coq proof, but I think my publication record buys me the label "computer scientist".

(I recognize you were probably usually your specific examples as examples of a kind, but it's that kind which I think is misinformed. You probably think a "computer scientist" must necessarily be a theoretician, which is not the case.)

> The actual job of a computer scientist is writing proofs in Coq

I was with you, but then this analogy went too far.

I think you would be saved by rephrasing to indicate a particular computer scientist. People are getting overly pedantic.

It's okay. That's how engineers and computer scientists work. The idea of "generalization" and "hyperbole" and "caricature" is often lost on us.

This is primarily why my technical blogging has slowed down significantly. Writing for an audience that cares more about details than The Point (tm) is often annoying.

Actually, to nitpick on the details, it's both. We care about the details AND the point. The details sometimes take you to The Point.

For example, I on your original post, I was trying to figure out if you meant "Computer Scientists are theoreticians" through the details. If you're not going to outright say something straight to the point, the details better be clear so that one can understand the implication.

That's the thing, there were no details, it was a caricature.

I've never heard of a person rewriting COBOL into Lisp in 2015. But I do personally know people who write Coq proofs and care about differences between strengths of various grammars.

Maybe that's the problem - that part came too close to reality and triggered people's spidey senses.

But most anti-cholesterol diets lower animal fat intake, not dietary cholesterol intake. Is this supposed not to work?

I had high cholesterol for years, I didn't take it very seriously because I'm otherwise healthy and I was eating healthy, but when I decided to take care of it I got it from around 210mg/dL to something like 140mg/dL just by changing all my meat/cheese to low fat alternatives as my doctor said. I am a big eater though, so maybe it doesn't make as much a difference for people that don't eat so much.

There were two suspected causes of high blood cholesterol-

1) dietary saturated fat (e.g. beef)

2) dietary cholesterol (e.g. chicken eggs)

Classical anti-(blood)cholesterol diets recommend avoiding both.

> My understanding is that a doctor's first job is to be risk averse. That's why they shy away from bleeding edge research and knowledge, and choose instead to rely on proven ways

I think it is more a matter of relying on what other doctors are doing and as well what they think their patients will tolerate.

I asked my cardiologist and primary care doctor before going on a well formulated low carb diet. they were both in favor of it but noted that they don't recommend these types of approaches, not because they don't work, but because people don't tend to stick with it.

In 3 months I lost 30 lbs (got a way to go still). My primary said that I have not indication now of prediabetes while I did prior to my diet.

For me I decided to take control of what I can in my health. Keep in mind your MMV.

> For me I decided to take control of what I can in my health.

But you did that cooperating with your doctors, which is how it should look. The problem with people taking charge of their own health is usually that they completely reject medical professionals altogether because they "know better". It makes exactly as much sense as when a manager decides not to hire a programmer, but instead buys himself a JavaScript book, because "how hard can this programming stuff be anyway?", or "the programming establishment still uses this old Ruby stuff, they don't know JavaScript is the state-of-the art solution!".

Knowing better than your doctor can lead to tragic consequences. Since we're in story-sharing mode: just last week my brother's friends saved the life of a guy who was after surgery that involved installation of stents, but for some reason didn't take the prescribed anticoagulants - he just kept the prescriptions stored in his bag and went happy about his life. He slipped up and admitted to taking no drugs on a checkup in the hospital. According to the doctor who was leading his case, he was hours from dying when they figured out what's going on.

You can count me in on the group that "is not taking the drugs proscribed by the doctor". Type 2 diabetic, and on my way back out of that disease.

And I made that informed choice. Statins do not work well with my family history. That was disregarded by doctor.

I also said I wanted to try a diet of low/no carbs and testing vigorously in a term called "eating to the meter". Instead proscribed Metformin. Also doc quoted wrong safe blood glucose limits, higher than that of where damage forms. Following his advice would guarantee me with diabetic neuropathy.

Now I wanted to see proof that what I asserted was safer.


Seems to work for me.

I want to comment on the version of your comment that you edited.

You stated that you believe a blood glucose of 140 mg/dl would cause diabetic neuropathy whereas your GP quoted a blood glucose of 150 mg/dl as causative of diabetic neuropathy.

It doesn't seem like things are as starkly different as that. Patients usually develop diabetic neuropathy over many years, so it's not clear that your GP would have 'guaranteed you diabetic neuropathy'.

Weird. I've edited no posts at least in the last week or so.(this post edited to add lines to show separation between studies.)

And yes, I cite 140mg/dL causes neural damage and shows itself as diabetic neuropathy. Proof.


>Diabetic Retinopathy Develops at "Prediabetic" Blood Sugar Levels

NIH News: Diabetic Retinopathy Occurs in Pre-Diabetes. http://www.nih.gov/news/pr/jun2005/niddk-12.htm

Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies Wong TY, et al Lancet 2008; 371: 736-743.

Association of A1C and Fasting Plasma Glucose Levels With Diabetic Retinopathy Prevalence in the U.S. Population: Implications for diabetes diagnostic thresholds Yiling J. Cheng et al. Diabetes Care November 2009 vol. 32 no. 11 2027-2032. doi: 10.2337/dc09-0440

Glycemic Thresholds for Diabetes-Specific Retinopathy: Implications for Diagnostic Criteria for Diabetes:The DETECT-2 Collaboration Writing group. Stephen Colagiuri et al. Diabetes Care Published online before print October 26, 2010, doi: 10.2337/dc10-1206

Hemoglobin A1c and Fasting Plasma Glucose Levels as Predictors of Retinopathy at 10 Years: The French DESIR Study. Massin P. et al. Arch Ophthalmol.2011 Feb;129(2):188-195.


> Beta Cell Destruction Begins at 2-hr OGTT Test Readings Over 100 mg/dl (5.6 mmol/L

Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Gastaldelli A; Ferrannini E; Miyazaki Y; Matsuda M; De Fronzo RA;Diabetologia 2004 Jan;47(1):31-9)


>Beta Cells Die Off in People Whose Fasting Blood Sugar is Over 110 mg/dl (6.1 mmol/L)

Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC.Diabetes. 2003;52:102-110.


>Blood Sugars Over 150 mg/dl (8.3 mmol/L) Kill Transplanted Beta Cells in Mice

ß-Cell Death and Mass in Syngeneically Transplanted Islets Exposed to Short- and Long-Term Hyperglycemia. Montserrat Biarnés, Marta Montolio, Victor Nacher, Mercè Raurell, Joan Soler, and Eduard Montanya. Diabetes 51:66-72, 2002


>Prolonged Exposure to Blood Sugars Over 140 mg/dl (7.8 mmol/L) Kills Human Beta Cells

Determinants of glucose toxicity and its reversibility in pancreatic islet Beta-cell line, HIT-T15.Catherine E. Gleason, Michael Gonzalez, Jamie S. Harmon, and R. Paul Robertson.Am J Physiol Endocrinol Metab 279: E997-E1002, 2000.


>One Hour OGTT Result over 155 mg/dl(8.6 mmol/L) Correlates with Markers for Cardiovascular Disease

Inflammation markers and metabolic characteristics of subjects with one-hour plasma glucose levels. Gianluca Bardini et al. Diabetes Care Published online before print November 16, 2009, doi: 10.2337/dc09-134

Edited: added lines for clarity between studies.

Your quotes are about destruction of beta cells (not neural damage). The 140 vs. 150 is a moot point: if you're diabetic, you're supposed to get your blood glucose fixed a lot lower than that.

Added: I read one of the studies, and it doesn't really controvert your doctors quote. It gives fasting glucose target a lot lower than 140 or 150 (as it should be), and 2hr glucose a lot higher than 150.

In essence, I think you're just interpreting these studies as you will without a proper medical training. My advice is: don't start experimenting with your life based on such weak foundation.

> It makes exactly as much sense as when a manager decides not to hire a programmer, but instead buys himself a JavaScript book, because "how hard can this programming stuff be anyway?"

Hey, worked out splendidly for Derek Sivers!

On the other hand your GP examined you and has an actual medical degree while you just read some articles on the internet...

Yes, this is a very good point that I try to keep uppermost in my mind. The thing is though that I'm not sure that having a medical degree and several years as a GP actually gives you much more of a grounding in non-drug therapies than someone who can read the original research (or in my case well referenced and balanced synopses of said research by people who's opinion I trust). Which is where my vague sense of disappointment comes in: the only intervention that a doctor within mainstream medicine seems to countenance is a prescription.

>actually gives you much more of a grounding in non-drug therapies than someone who can read the original research

I don't think one can actually "read the original research" (with the all the prerequisite and pressupossed knowledge that entails) without either having been to medical school and have similar training of his own to such a level.

Having access to said research and being able to read it (in the nominal sense) is not the same as actually being able to "read it" (e.g. understand all that it entails, even things that are not explicitly said).

Even less so for "well referenced and balanced synopses of said research from people one's trust" unless said people are doctors AND have examined you personally. Some well respected pop science journalist's online synopses won't cut it.

In case you doubt your doctor's results, which can of course be not up to par (doctors are fallible too) the prudent thing to do would be to seek counsel with another doctor(s) for a second opinion.

I agree here, though I personally wouldn't trust a single doctor to him/herself be able to parse, as you say, the research.

Research is written at a peer level and most doctors are not trained or don't care to know how to interpret the results of research. Not to mention that the vast majority of research is extremely specific.

>Research is written at a peer level and most doctors are not trained or don't care to know how to interpret the results of research. Not to mention that the vast majority of research is extremely specific.

Most research (the vast majority) is also bogus too. Until it's distilled to common practice, people shouldn't really touch it with a bargepole.

See my other lengthier comment on this.

I read your larger comment and I don't agree with most of what you're saying as a generalization.

This though:

> Until it's distilled to common practice, people shouldn't really touch it with a bargepole.

I can agree with. Most research if it's not done in the clinic and proven, has parameters so specific that it is impossible to apply to a single member of a population without that member having the exact parameters that the original research had.

Even then, the original research was probably done on some animal and not a human.

Then we do translational testing/research which gets done on a more human like animal and if we're lucky some human samples (given a disease). Then the clinical trials etc.

Though a review of the current literature can be beneficial. But you'd still need to have training to be able to interpret what you're reading.

Yes you're absolutely correct, I'm waiting for a referral to a specialist at the moment.

WRT to my examination though: it didn't go beyond having bloods done. There was no other investigation other than, wow your LDL is really high.

My go to source for understanding this stuff is Peter Attia [1], and a few other independent researchers.

[1] http://eatingacademy.com/nutrition/the-straight-dope-on-chol...

I've got some friends who do medical research, and from what they say, "translational research" (getting the latest research into the hands of the doctors actually practicing medicine) is a HUGE problem.

I have been advised that if I (or a family member) ever gets some medical condition, that if I do a few hours of reading up on the latest research on that condition, chances are that I will be better informed on that condition than my GP.

Probably, but your ability to process the information is severely limited to someone who has be trained on how to do so. And I'm not saying that your doctor has been trained to do so.

My faith in Doctors is pretty much at an all time low.

I kept having bouts of extreme pain with really strange symptoms, Doc's said Reflux but I kept saying it didn't fit the pattern, a dozen AE (ER) visits later and I got a Doc who told me to insist on an MRI.

Turns out I have Syringomyelia, a serious and rare spinal condition which the radiologist spotted by accident as it was on the edge of the scan, he then did a bunch more images and they saw the syrinx.

The next doc I saw I needed an endoscopy and they said the results where abnormal, so I looked into the condition, when I went to see the gastro doc I asked him if the cells where "high" or "low" grade dysplasia and his snarled response "Oh, trying to be a doctor eh", "no, just trying to be an informed patient".

I requested a different gastro doc after that, I read everything I could get my hands on and I'm not stupid, I understand my condition well enough to ask good questions at least.

So yeah, not a massive fan of Docs at the moment.

I can relate to this.

I feel that the chasm between the lay person and the MD has widened tremendously in our lifetimes (I'm in my 30s).

This also, unfortunately has made the average patient be almost completely uninformed. They demand medication to cure their, self-inflicted, ills, or try to diagnose through Web MD.

I for one will educate my children and will continue to educate myself to not require an MD on every occasion.

But I know that I'm not an MD and I was not trained to diagnose. I'm glad you found doctors who could give you a correct diagnosis that you can lean on to help you through your own search for the truth. I feel this is the best solution at the end of the day, for patients and doctors to be partners.

* My dad is an MD and my wife is a biological scientist which really puts me at an advantage.

>I've got some friends who do medical research, and from what they say, "translational research" (getting the latest research into the hands of the doctors actually practicing medicine) is a HUGE problem.

That's a good thing too.

Unless the "latest research" actual distills down to common practice, it's usually unproven junk, even if it managed to get published in "peer reviewed journals".

In fact several meta-studies have found over 80% of the papers that are published in such journals are wrong and/or non-reproducible. As for research results that made it to Nature or similar pop science magazines those are usually even more journalistic than scientific.

Think of a research "getting into the hands of the doctors actually practicing medicine" as a filtering process to weed out the BS.

Here's how it works:

A team of some inexperienced postgraduates hastily follow some idea tossed around by a professor who doesn't really follow their progress or care that much, but who'll gladly slap his/hers name on the final paper. If there's a need to secure grants, the paper will tackle some important topic and better have good results.

In the way, they make one or more methodological errors, and finally send their paper to some journal. The journal editor might be friends or exchange favors to the professor, and will do what he cans to get favorable reviewers, anonymous or "anonymous".

Not that the reviewers will go into much bother checking it out, unless the paper is evidently crap. After its published, some pop science journalistic hack will cover it in the cliched "breakthrough story" format, also giving a full portrait of the professor as a restless scientific maverick (even though he merely signed the paper). The editor will then slap a blockbuster-like title to the story, and readers will enthuse about the possibilities.

Several months/years later, 3-4 other papers will tear down that one, and the cycle continues. Though sometimes wrong papers manage to get cited for decades without anyone bothering to redo and verify the original research.

> In fact several meta-studies have found over 80% of the papers that are published in such journals are wrong and/or non-reproducible.

And are you able to interpret these studies to see their flaws? What I would focus on more is to look at something called Retraction Watch.

> As for research results that made it to Nature or similar pop science magazines those are usually even more journalistic than scientific.

I'm excluding the articles written by journalists here. But I don't think you know how hard it is to get a paper published in Nature.

> Think of a research "getting into the hands of the doctors actually practicing medicine" as a filtering process to weed out the BS.

Rather, weed out the danger. And this control, though also flawed to a degree, is very good in my opinion.

> Here's how it works:

There are many things wrong with the whole process, but your view described here is a little too patronizing to actually get your point across.

> Not that the reviewers will go into much bother checking it out, unless the paper is evidently crap.

The reviewers, depending on the quality of the publication, should be experts in the field that the paper is being published from.

And finally:

> Several months/years later, 3-4 other papers will tear down that one, and the cycle continues.

Yes, this is called scientific progress.

While that is true, the GP (and even specialists) use a different optimization criterion than yourself (proverbial you): You prefer to minimize false negatives with some exceptions about false positives, whereas they prefer to minimize overall error rate with some exceptions -- and that goes very deep into their training, to the point of being blind to this preference.

E.g., while at med school, they are warned against Zebras[0] so much that while practicing they will often ignore anything with a 1-in-a-million-chance unless the false-positive rate is zero. It does minimize the overall error rate, but for the person who has the 1-in-a-million condition, this is no comfort -- and that person is often in a position to evaluate that condition better than the GP (if they are scientifically literate).

I have been told by a senior doctor at one of the leading US hospitals to "cut the internet cord so that I don't confuse myself as I am not trained to understand the articles I find". Turned out said doctor did not understand the statistical inference criterion, and I did -- unsurprisingly, since I have the mathematical background, and they do not.

[0] https://en.wikipedia.org/wiki/Zebra_%28medicine%29

> read some articles on the internet...

There is a difference between reading something on WebMD and reading something on Google Scholar.

The one tells you, "Go see a doctor" and the other one tells you very little, if you don't know how to interpret what it's saying.

The interventional studies which have clearly demonstrated an effect of diet on cardiovascular risk are the Lyons Heart Study (for prevention of a second event after a first) and the PREDIMED study (for primary prevention). The broad takeaways are that a Mediterranean diet may reduce risk, and more specifically, supplementing a diet with extra-virgin olive oil and some nuts seems to be beneficial.

The magnitude of the effect of diet (for people without specific monogenic dyslipidemias) is not large, probably in part because most cholesterol in the body is produced by the body.

In many circumstances – especially in the case of familial hypercholesterolemia – diet and exercise will not achieve an acceptable risk reduction. I would conclude by saying that your GP could have engaged with you more effectively to achieve a mutually agreeable outcome. Nevertheless, if you think "cholesterol == unhealthy", this is an acceptable gestalt understanding under the modern Western diet.

I have a friend who is a pharmacist, and she warned strongly against statins. Among other drawbacks, statins kill sex drive.

Take matters into your own hands and change your diet. Nothing beats a high anti-inflammatory whole-foods plant-based diet. Check the research.

Indeed, that's what I've done. I've completely eliminated sugar and I've increased my veg intake. As of the end of last week urine strips indicate that I'm in ketosis. I'll have another set of bloods done this week before I go to see a specialist probably after xmas. I intend to take a very self experimental approach with this. At the same time, if it does turn out that I'm one of those people who doesn't metabolize saturated fat well, or I do in fact have a genetic mutation then I'll also have to consider the drug route I suppose.

"A plant-based diet is a diet of any animal (including humans) based on foods derived from plants, including vegetables, whole grains, legumes and fruits, but with few or no animal products."


How can I get in contact with you? I'm in the same boat.

Doesn't the TFA address this and basically says that there's no anti-inflammatory diet except a strict liquid one delivered through the nose?

> whole-foods plant-based

There should be a lot of veggies, of course, but people seem to think that meat is evil and bad for you. There's a lot of very good reasons to eat lean meats, fish and grass-fed ruminants.

Well, there are plenty of recent studies that suggest that high-protein diets, and ones with a lot of meat in particular, are associated with increases in the rates of several cancers. But to just to play devil's advocate, why eat meat when you don't need to? I've seen some studies suggesting eating fish has health benefits (though there's the problem of pollution in the oceans), but I can't say I have seen anything that would actually recommend red meat, no matter how wholesome the source.

The only issue with red meat would be the carcinogens that come from burning or charring. Saturated fat isn't the evil the FDA once thought it was.

There are also a ton of studies that suggest that one of the leading indicators for wellness and longevity is total lean mass, and protein is a fundamental building block for this. There simply isn't a way to eat a whole foods diet and put on muscle mass--you have to supplement with a bunch of pea protein and the like. And vegan/vegetarian diets are notoriously high in carbohydrates and low in fat and protein. Not necessarily a great recipe for wellness.

Add to that the androgenic affects that meat (and dairy) produce, and there isn't much that compares. And part of the reason why meat carries some association with cancer is its growth producing effects.

Of course, overeating and being sedentary is one of the worst things you can, regardless of if it's meat or not.

> And vegan/vegetarian diets are notoriously high in carbohydrates and low in fat and protein. Not necessarily a great recipe for wellness.

Please cite a reputable source for this outlandish claim. You can check my post history for some links to non-profit health organizations such as WHO, which recommend the majority of caloric intake to come from carbohydrates, and to limit fat/protein intake to 15% or less each.

Isn't it rather dangerous to give sweeping medical advice to strangers over the internet?

I love the thought that "eat more vegetables" constitutes dangerous advice.

The instructions were more along the lines of "eat nothing but vegetables and ignore your doctor".

Most doctors get exactly zero nutrition education and the few which do are very limited and usually heavily influenced by Big-Ag and Big-Pharma. Certainly "only eating vegetables" is not sound advice, but it's not unreasonable to second-guess your doctor's diet recommendations.

The GP said:

> Nothing beats a high anti-inflammatory whole-foods plant-based diet.

The word "Nothing" implies that this comment goes beyond diet advice in the realms of alternative medicine. This kind of advice is really dangerous.

Well, they're strangers..

It comes down to diet. My LDL is 66 and my HDL is 75. I don't eat eggs, meat, or cheese. Basically, nothing that has cholesterol.

My numbers will probably be even better this year. I have looked at /r/keto and /r/paleo. Their cholesterol numbers aren't good.

Recent research suggests that cholesterol directly in food isn't a major problem because most of it passes through the digestive system untouched.

The problem is actually cholesterol produced by the body using other substances. 80% or more of the cholesterol in your body is produced by your body, no more than 20% of it comes from your diet unless your diet is particularly unbalanced in that manner. The reason cholesterol in people's diet got the blame is that there is often a strong correlation between the foods containing substances that do cause increased cholesterol in the body and foods containing significant amounts of cholesterol, and a similar correlation between certain lifestyle options that are risk factors for heart problems generally and eating those foods.

So blindly reducing cholesterol in your diet is not useful and may lead you into a false sense of security - you could still be taking in the other stuff and living your life in a way that will encourage the body to produce too much cholesterol itself.

It's not even all that recent, I took some nutritional biochem classes in the late 70's and the professor said repeatedly that dietary cholesterol was not a big factor in what was in your blood as the molecule was too big to pass through the intestinal wall. What is made by the body (generally from a fatty diet) matters.


"The cholesterol in eggs not only worsens the effects of saturated fat, but has a dramatic effect on the level of cholesterol and fat circulating in our bloodstream during the day."

I can't reply to the comment below me, but he does cite all the studies in his videos.

I just had a click round that website. It's just the kind of place that I avoid like the plague. It seems hopelessly biased, as does the author. I didn't come across one link to an scientific study, and it was immediately obvious that there's a serious anti animal products agenda going on and no disclaimer.


It's quite apparent you didn't actually look through the website, or you are just a low-carb shill (if so, please see http://www.atkinsexposed.org - the same dietary nonsense seems to be repackaged by each generation). The NutritionFacts website is literally about published peer-reviewed research, not the author's own personal opinion, nor some "agenda" (pushed by whom, Big Broccoli?)

In case you aren't trolling, try disabling your ad-blocker. Each page has citations with direct links to the studies mentioned in each video.

If you can figure out the actual studies from those sites, please provide links to them or their abstracts, at least.

Otherwise, all that is being provided are two websites pushing books, and their failure to even give usable locators to the claimed studies in text footnotes on the pages (if not clickable links) is suspicious.

Like I've already said, the studies in each video on NF are linked directly. I don't see how they're "pushing books" on anyone - having read both of them, I can tell you the information they offer isn't much different than the free site content anyway.

> Recent research suggests that cholesterol directly in food isn't a major problem because most of it passes through the digestive system untouched.

Could you please link to some of this research so we may all review and benefit from it?

Most of my "knowledge" on this matter comes from physical copies of NewScientist and similar (my bathroom reading), rather than papers directly or something I've got readily bookmarked online. I'll see if I can find that particular issue when I get home, if I can I'll extract the references and pass them on.

Perhaps you could first identify your presumed mechanism of action that converts dietary cholesterol into LDL.

Dietary cholesterol is linked to blood LDL, because eating phytosterols - which inhibit cholesterol absorption in the gut - will lower your blood LDL. The mechanism can be found online.

It's quite upsetting to see you're being downvoted for no apparent reason, with no logical rebuttal. I've also cut all animal and processed foods from my diet (it's much easier than it seems at first) and my cholesterol levels are similar to yours - in the optimal LDL range of 50 to 70 (https://www.ncbi.nlm.nih.gov/pubmed/15172426).

The problem is now that I'm not even sure whether I should agree with what a "good" or "bad" number is for LDL or TC. The recommended number seems to fall every few years, and I'm unsure how much of that is based on good research or industry pressure or what.

I've stopped eating all together and my stats are out of this world.

Why the snark?

Somehow LDL-cholesterol has come up in this thread about inflammation.

The article here offers a highly speculative opinion regarding the role of inflammation across many diseases. The luminaries in cardiology cited in this article ran trials which many of us consider to show that, rather than inflammation being important, any reason to start statins is a good reason.

The genetic data currently supports very little role for inflammation in important diseases like coronary artery disease, whereas there is crystalline evidence supporting the connection between LDL-cholesterol levels and mortality. Interestingly, when genetics are invoked and mere epidemiology is reassessed, there is no clear atheroprotective role of HDL cholesterol.

The treatment of statins is very much like the treatment of vaccines: dismissed in a pseudo-intellectual manner by people who know a lot (just not about the subject at hand).

>there is crystalline evidence supporting the connection between LDL-cholesterol levels and mortality

The connection is very far from crystalline ([1],[2]) The strong association only seems to appear when considering groups with super high LDL-C levels, likely due to FHC. In any case, the typical approach, statins, has very little positive affect on individuals without pre-existing heart disease ([3],[4])

If vaccines had the same side effects and poor absolute risk reduction that statins have, the anti-vaxers might actually have a point.

[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750440/

[2] http://www.crlcorp.com/wp-content/uploads/2013/06/JIMlipidsm...



In controlled, randomized trials and in genetically-driven studies (the two most powerful tools that we have to assess causality), almost all factors that reduce LDL-cholesterol lead to reduced ischemic heart disease and death.

Your commentary about statins being primary useful for secondary prevention (in those who have already had a heart attack) was true until a couple decades ago, but there is now evidence demonstrating that statins reduce primary events (though at a high NNT depending on the population's risk). Naturally, the higher risk the population, the more benefit and lower NNT you will see from any intervention.

A classic genetic study, for example, is that of Hobbs and Cohen looking at PCSK9 variants [1]. People with loss of function mutations in PCSK9 have lower LDL-cholesterol. These people have an even lower risk of ischemic heart disease than you would expect based on the degree of LDL-cholesterol lowering. This is surmised to be due to the lifelong exposure to low LDL-C, though the actual reason is not currently known with certainty.

1 = http://www.nejm.org/doi/full/10.1056/NEJMoa054013

The real question is, though, is drug therapy something that should be pushed on otherwise healthy (non-FHC/high risk) individuals in order to reduce mortality. The PCSK9 research paper you linked has the percentage dead after 15 years (starting at an average of 55 yr/o) at 10.7% for those without the mutation and 8.3% for those with it.

Assuming they actually work identically to the mutation, maybe one could argue that the $$$ cost of the new PCSK9 targeting drugs will be worth it to save 2.4%, but we have zero long term data on their safety. There is certainly some evidence [1] that the risk for diabetes could be higher...much like the current statins.

I don't think we have anything even approaching a complete picture on the interplay between CHD, cholesterol, and overall mortality. Until the picture becomes clearer, it doesn't seem prudent to push drug therapy as strongly as it typically is.

[1] http://www.ncbi.nlm.nih.gov/pubmed/20026049

The coincidence of statins falling out of patent and the rush to develop PCSK9 drugs is not lost on me.

To rephrase the exact same data, 15-year mortality is ~30% higher among those with the normal variant compared to those with the cholesterol-lowering variant. That is an enormous mortality effect.

Based on the mechanism by which statins are postulated to cause diabetes (and LDLR-dependent mechanism), PCSK9 inhibitors may also cause diabetes, though it's not yet known. From a mortality perspective, this is irrelevant because we know that statins (and PCSK9 mutations) reduce mortality despite (probably) causing diabetes.

The timing of statins falling off patent is essentially uncorrelated with anything - there was a multi-year gap with atorvastatin off patent before the PCSK9 inhibitors were approved, which makes no sense if you would like to invoke a patent conspiracy. With the advent of genetically-informed early phase research, you will continue to see new drugs come out at an increasing frequency (reversing the trend over the past few decades of fewer approvals).

The link from cholesterol -> CHD -> mortality is as clear as anything in biology (clear enough for the basis for this work to have won a Nobel prize decades ago).

I think this is a bit unkind:

> dismissed in a pseudo-intellectual manner by people who know a lot (just not about the subject at hand).

I'm the one who's potentially sick here, and this (perhaps wrongly) smacks of appeal to authority. What I absolutely don't want to do is disregard medical opinion, but neither am I inclined to abdicate all responsibility for my own health and well being.

> The genetic data currently supports very little role for inflammation in important diseases like coronary artery disease, whereas there is crystalline evidence supporting the connection between LDL-cholesterol levels and mortality

I'd be very interested in learning more about this, do you have anything you could recommend? I'm fully aware that the majority of what I read on the internet is likely to be along the lines of "don't sweat it, eat natural and you'll be fine" and I'd very much appreciate some exposure to the opposite point of view too.

>> The genetic data currently supports very little role for inflammation in important diseases like coronary artery disease, whereas there is crystalline evidence supporting the connection between LDL-cholesterol levels and mortality

> I'd be very interested in learning more about this, do you have anything you could recommend?

I'll let the OP chime in if I'm wrong but I believe s/he is referring to the numerous genetic association studies[1] that have implicated LDL biology in coronary artery disease. Look at ref. 2 for a publicly-accessible review. The article details the genes that have been associated with coronary artery disease, none of which appear important for inflammation.

1. https://en.wikipedia.org/wiki/Genome-wide_association_study

2. http://circ.ahajournals.org/content/128/10/1131.full

In talking about pseudo-intellectual dismissals, I am appealing to the prior news.YC discussions about middlebrow dismissals, which would have been better wording. Sorry about that. How is what I mean different from an appeal to authority? Mostly it has to do with the type of evidence selected by statin "opponents", which tends to be of lower quality.

As for studies that I find instructive, here are a few:

People with loss of function mutations in PCSK9 have lower LDL-cholesterol. These people have an even lower risk of ischemic heart disease than you would expect based on the degree of LDL-cholesterol lowering. [1]

Mendelian randomization demonstrates that genetic scores for LDL cholesterol associate with reduced risk of myocardial infarction (suggesting causality, since cholesterol doesn't reverse-cause a genotype).[2]

IMPROVE-IT showed that a non-statin medication (ezetemibe) added to a statin regimen further reduced the risk of second heart attacks after suffering a first heart attack. This is probably the clearest experimental evidence to date that suggest it's not only statins that reduce cardiovascular risk, but LDL-cholesterol reducing agents more generally that lead to reduced risk of heart attack. [3]

This is a very contemporary summary of genetic and clinical trial data; there is a wealth of older data that I won't get into.

1 = http://www.nejm.org/doi/full/10.1056/NEJMoa054013

2 = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419820/

3 = http://www.nejm.org/doi/full/10.1056/NEJMoa1410489

[T]his (perhaps wrongly) smacks of appeal to authority.

Don't dismiss appeals to authority so easily. As it happens, not giving extra weight to experts in proportion to their track record is a provably suboptimal strategy in an adversarial setting (see e.g. [1]). So, in this sense, deferring to trained medical opinion might in fact be the most responsible thing to do.

Note however the bounds in [1] also (indirectly) imply you are better off with a diverse ensemble of expert advice. So if you can afford it, always get a second (or third) reputable medical opinion. And weigh their advice accordingly.

[1] http://www.mit.edu/~9.520/spring08/Classes/online_learning_2...

This is correct. I reference one of the Mendelian randomization studies in my comment [1].

1 = https://news.ycombinator.com/item?id=10739687

You might want to read the book Why Zebras don't get Ulcers by Robert Sapolsky. It's about stress, all aspects of it. So it's not about inflammation, although inflammation means stress and in that regard it is covered - you might find it interesting.

Be prepared for lots of chemical terms, but don't let that hold you off - there's enough interesting stuff to read. It has lots of interesting information.


It's hard to take the evidence at face value though, given the historically malevolent influence of big pharma on accurate publishing of trial data (SSRIs, vioxx etc), the significant links between the key trialists and the drug developers, and the lack of transparency in the data.

At this point the argument about statins can only be solved by opening the data.

What you are saying is true to the same extent that it is true about any drug. Statins are unexceptional in this regard, except that they have a lot more lines of evidentiary support than most drugs due to the importance of coronary artery disease.

Even ignoring statins, again, the genetic evidence paints a clear picture of the causal role of LDL cholesterol in coronary disease. The jury is largely still out on inflammation.

Agreed. However in the case of statins, the benefits for an individual are very slight, even if the population benefit is large. This means that this sort of uncertainty about side effects can make it rational for an individual to abstain from taking statins.

>The treatment of statins is very much like the treatment of vaccines

I don't think that's an accurate comparison. There's not really anyone in the healthcare industry that would argue against vaccines but there are plenty professionals with qualification (mds, pharmacists, etc) that are against the broad use of statins.

The treatment of statins is very much like the treatment of vaccines: dismissed in a pseudo-intellectual manner by people who know a lot (just not about the subject at hand).

This. It's rather unsettling to see so many well-meaning posters gleefully rejecting prescribed statins. They are playing with their health.

When the "system" becomes an adversary in one's fight for health, as a result of cost, restricted access to doctors and their time, and when an ocean of credible (and non-credible) information is available relating the mechanistically uncertain world of medication, it is not surprising to see many people feel as if they have looked behind the curtain in a wizard of Oz sense and begin reaching for alternatives. Statins are probably among God's greatest gifts to most people with high LDL as clinical trials show, but many in the HN community might be willing and able to make drastic lifestyle changes that other individuals are incapable of. Many entrepreneurial and data-driven types have the thick headedness to be that 1% of patients for whom lifestyle changes work, or at least we like to think so. In any case, starting a statin (in the case below) and then proving to oneself that one is supreme commander of diet and metabolism may be the optimal route. The issue lies in which pathway to choose for our attempt at supreme commandership--ketogenic, paleo, low trans fat, etc. Once again, the results are unclear in some trials and the mechanisms are as elusive as ever, which is why we reflexively search for explanations in the fey realms of inflammation, microbiome, epigenetics, and so forth. Addendum: Most clinical trials are aimed at helping the general population with a specific condition; it would be interesting to try clinical trials of diets in only highly educated and fairly affluent people who know python (usually not part of the subgroup analysis).

I had a long reply to your previous comment written out but you deleted before I could post and it got lost. But I guess what I was saying does boil down to this. I don't have a great deal of faith in the shallow, one size fits all, drug based approach I was offered. I do intend to look at wider options, and you're right that there's a lot of information available. However, I don't intend to do a Steve Jobs. If it looks like I've sustained damage to my arteries already or I can't find an intervention that works then I'll revert to the suggested route.

After I read your other comments I deleted the first post because I realized you are knowledgable about many issues I brought up and it was non-contributory, apologies. I wish you the best in keeping healthy!

Those guys at Harvard...


They must think we still need to learn a lot more about the human body.

"This suggested that elevated cholesterol isn’t the only factor at work in cardiovascular disease, and that in some cases statins, acting as anti-inflammatory agents, could be used to treat the condition."

I noticed that you're a medical resident in Boston. I bet if you look back in 40 years, it'll look like we were in the Stone Age.

Inflammation will probably turn out to be some combination of a fad and a real phenomenon that is simply a symptomatic mask for a host of different underlying issues. For example an allergy to dairy and a GI infection are different conditions but both present with inflammation.

And by the way, we don't really know why allergies develop at all. The best treatments simply tire them out, or suppress the symptoms. The immune system in general is poorly understood, so perhaps it's not surprising that people have trouble thinking past "inflammation" in general.

The idea that the human body has some pervasive fault or malfunction that can be addressed by adherence to an ascetic diet is not really new. One can find similar accounts going back hundreds of years in Western medicine, and even farther back in religions. For some reason, our minds seem to incline that way.

And it's true to some extent: obesity makes almost any disease worse, and obesity can be avoided or reduced by an ascetic diet. That is true for almost every human being, which is the highest standard that medical advice can meet.

Unfortunately, most diet advice does not meet that standard. By which I mean, it's easy to find counterexamples to most diet advice. A diet might tell you to avoid dairy, but there are millions of people who consume dairy and yet are perfectly healthy. A diet might tell you to take fish oil, but there are millions of people who never do, yet are perfectly healthy. A diet might tell you to avoid gluten, yet there are millions of perfectly healthy people who eat gluten every day. And again--I'm not talking about real allergies here, I'm talking about general diet advice.

The future seems pretty clear to me. We know that each person's genetic code is unique. We know that each person's genetic code is expressed in unique ways due to epigenetics and other factors. We know that each person has a unique collection of gut bacteria, skin bacteria, and other hangers-on.

Ultimately, if we want to create more perfect health, we will need to learn how to collect each person's unique information, tie it reliably to health outcomes, and then introduce highly personalized therapies based on that information.

The demand on information technology will be enormous. This will be a growth industry for humanity for at least the next century, I bet.

Inflammation can fan the flames of depression

"In the health area of psychology at Rice, we're very focused on the intersection of health behavior, psychology and medicine," said Christopher Fagundes, an assistant professor of psychology and co-author of the paper. "One thing that we're particularly interested in is how stress affects the immune system, which in turn affects diseases and mental health outcomes, the focus of this paper."

The authors found that in addition to being linked to numerous physical health issues, including cancer and diabetes, systemic inflammation is linked to mental health issues such as depression.

Among patients suffering from clinical depression, concentrations of two inflammatory markers, CRP and IL-6, were elevated by up to 50 percent.

Fagundes said chronic inflammation is most common in individuals who have experienced stress in their lives, including lower socio-economic status or those who experienced abuse or neglect as children.

Other contributing factors are a high-fat diet and high body mass index.


statins-for-cholesterol is a hugely profitable business pushed hard for decades by BigPharma, going back to a single faulty "study" in the 1950s, after Eisenhower's heart attack.

My opinion is that statins-for-cholesterol, obsession with cholesterol is as big of a medical scam, a BigPharma misdirection-for-profit, as BigFood's "low-fat" and "whole grain", and gluten scams.

Cholesterol is essential, so much so 90% is produced by the liver without any dietary consumption.

Cholesterol + lipids + calcium sticking to arteries is a reaction to an injury, mostly from systemic, low-grade inflammation. High blood pressure also injures arteries, also causing cholesterol plaque.

Some people with high cholesterol have no CVD, while some people with low cholesterol die from CVD. Maybe cholesterol isn't the problem?

Aspirin's help with CVD was initially thought to be due it blood-thinning effect, getting blood through narrowed arteries, but then its anti-inflammatory effect was more reasonable. btw, statins are also anti-inflammatory (aspirin and similar are cheaper).

Systemic inflammation reduced by aspirin (or statins), less injury to arteries, less plaque.

Systemic, low-grade inflammation also reduces insulin sensitivity, so the body produces more insulin, which is a really nasty hormone. result? adult-onset Type II diabetes.

So "I think" watching inflammatory bio-markers is more important than watching cholesterol, as one could take away from the New Yorker article.

An alkalizing, anti-inflammatory diet is key, complemented by both moderate resistance work and moderate cardio exercise, which also reduce inflammation.

"life-style" of diet and exercise is your best "Heal Thyself" strategy, not BigPharma.

btw, chronic, systemic, low-grade inflammation causes chronic high-levels of cortisone (derived from cholesterol) to reduce the inflammation, and wreaks havoc on the immune system, which of course causes inflammation as a response to injury or foreign matter.

> An alkalizing, anti-inflammatory diet is key

Can anyone cite a peer reviewed study / documentation of "alkalizing" diets? I've attempted to trace this idea back to anything scientific, and always eventually came up with "well, someone I trust once told me ...".


one of the nasty results of a acid diet (sugar, mammal/fowl products, etc) is that the body will buffer the serum pH on the low side to stay within the body's healthy pH range by robbing calcium from bones and teeth.

Thanks, but that's not what I'm after - let me rephrase my question.

Acid/Base homeostasis is obviously important, and the body works hard to maintain it, no question about it. However, there is a claim (e.g. the one you made) that an "alkalizing diet" is healthier in some way than a "common" diet -- and I'm looking for a reference for that.

I have found references saying that ingesting sodium bicarb (the ultimate alkalizing agent) was shown to help with very controlled amounts and strenuous exercise, and was otherwise either useless or harmful. I have found many claims, but not one properly supported by an experiment, that an "alkalizing diet" (which often includes acids like lemon juice or apple cider vinegar in those descriptions with some hand waving) is good for you.

So, my question is: I am trying to understand the origin of the "alkalizing diet" argument, and see whether it is science, pseudo-science or myth; can you help me with that?

"statins-for-cholesterol is a hugely profitable business pushed hard for decades by BigPharma"

The vast majority of statin scripts are generics, and quite cheap. "Big Pharma" now lacks a profit motive there.

What are your credentials for making these statements?

I can read, and I read a lot

I am not really sure that inflammation is a single entity. Today is is fashionable to claim everything has something to do with inflammation, but I remember the time a medical mixup caused me to get a high-sensitivity CRP test after I had just smacked a quadricep muscle enough that I was off my feet and on painkillers for a week and my CRP reading was as low as it can be.

I think there's something to the acid/base thing and I think it's connected to inflammation.

I recommend a vegan diet. Juice celery, and everything else.. drink it soon after juicing don't put in tha fridge. Juice about a half pound of raw cannabis per week if you can (it's not cured so it won't get you high)

and uh.. drink lots of h2o.

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