Depression is an inflammatory disease; where does inflammation come from? [pdf] | Hacker News Reader

Depression is an inflammatory disease; where does inflammation come from? [pdf]

researchgate.net

163 pointsgwern208 comments

  Omega-3 fatty acids, which are important components of
  many healthy foods, such as seafood, nuts, legumes and
  leafy green vegetables, act to reduce inflammation

Score another point for fish oil supplementation, on top of the already enormous pile of scientific research showing it to be a miracle chemical (and I definitely don't say that lightly) [2]. Seriously, if you aren't getting enough omega 3 fatty acids, either from regularly eating lots of fatty fish or through supplementation, you're seriously missing out on some good stuff. Among supplement enthusiasts, it's consistently declared to be one of the only supplements that's actually useful. I prefer the liquid form [1].

[1] http://www.amazon.com/Now-Foods-Omega-Lemon-Flavor/dp/B001B4...

[2] http://examine.com/supplements/Fish+Oil/

Edit: added [2], a well-written examine.com page summarizing fish oil effects

It's not that fish oil is an unalloyed good, mind; just that we get way too much Omega-6 in western diets, and it seems that Omega-3 "cancels it out." In cultures with balanced Omega-3/6 intake, like Japan, fish oil has no benefit.

Correct. The alternative to pounding fish oil supplements is simply stop eating so much refined seed and vegetable oils. A ratio can always be fixed in at least 2 ways obviously.

It's harder than that. Our food supply has changed; sixty years ago when cows ate grasses, beef naturally had some omega-3s in it. Now that their diet is largely corn, beef brings virtually all omega-6s.

Ditto for "shelf-stable" foods. Omega-3 fatty acids go rancid at room temperature, so many packaged products have had the omega-3-based fats removed so they'll last longer on the shelves.

Source: my wife, who has a PhD in nutrition.

My understanding (from investigating this a couple years ago) is that grass-fed beef, while higher in O3's than corn-fed beef, is not a particularly significant source of dietary O3.

Check out http://www.ncbi.nlm.nih.gov/pubmed/16500874

I think that is accurate. I only meant to use beef as an example of how our food supply has changed, not to suggest that beef is any sort of good source for omega 3s.

Correct me if I'm wrong, but it's not just that grass-fed beef is higher in Omega 3, but lower in Omega 6. So it's not just about Omega 3 intake, but the ratio between the two.

I believe that is the main reason it is labelled as such and more expensive than regular grain fed beef. Same with free range/cage-free eggs.

Wild Salmon should be a good omega-3 source, while Norwegian grown salmon is probably not.

Here is a link to small study about this.

> The results show a little more of the healthy long-chain marine omega-3 fatty acid forms known as EPA and DHA in farmed salmon than in wild salmon.

> [..]

> “Indeed, there is a larger amount of omega-6 in farmed salmon. You get nine times as much as when you eat wild salmon,” says Research Fellow Ida-Johanne Jensen at the Norwegian College of Fishery Science.

http://sciencenordic.com/farmed-salmon-retains-good-fats

So it says that farmed salmon has slightly more O3 and 9x more O6. But how are the absolute ratios, is the salmon O6 content enough to matter if we want to balance out the presumably much larger O6 already in our bodies?

There's a certain optimal ratio between the various omegas. You could get too much or too little from any particular kind. It just happens that modern diets have too much omega-6 and not enough omega-3.

Plus the Japanese diet tastes better than a fish oil gel cap ... speaking of which, does this mean that the incidence of depression in Japan is low?

Well, according to this article about a recent study:

http://www.washingtonpost.com/blogs/worldviews/wp/2013/11/07...

Japan has the lowest rate of diagnosed cases of depression of any country in the world (<2.5%). Of course, there could be other causes for this, and the accuracy of how well the diagnosed rate represents the actual rate is an open question. In particular, in east asian countries thre seems to be a cultural taboo against admitting mental illness and seeking treatment in order to get diagnosed in the first place. The fact that Japan has one of the highest suicide rates of any country in the world is an especially telling statistic that the diagnosed rate may not be telling us everything.

A healthy diet is really not a remotely sufficient substitute for a healthy social context.

One of the reasons there's a link at all is because we often eat with people.

It may not be that deterministic, as if it's either diet or social context. One thing can feed on the other.

It can start as an emotional response, deflagrating an inflammatory process, revealing the nutritional deficiency. Or it can start with a nutritional deficiency, deflagrating an inflammatory process, which the brains reads as depression.

This mechanism is already seen regarding stress and magnesium. High stress -> Mg depletion. Low Mg -> Stress symptoms.

I wonder if we can make the assumption that a suicide must have come from depression. Or at least, I'm not sure if the reasons/depressions experienced in Japan are comparable to other countries. I'd also agree that the admittance of mental illness may be lower than the actual. There are some pretty strange conditions out there, like hikikimori.

Right, I'm not saying that suicide necessarily comes exclusively from depression. Obviously there are other cultural factors at play in Japan that may lead to higher suicide rates. Just that the massive discrepancy between suicide rates and diagnosed depression rates is suggestive of the fact that the actual depression is at least somewhat higher than what we see.

I work in the pharma industry in Japan and I can confirm that depression is massively under-diagnosed, and that the market for depression treatment is expected to boom in the coming years. So much, that they are now doing TV campaigns to encourage people to be diagnosed. So yeah, don't count on the current statistics to tell you anything significant, there are many cultural barriers at play in Japan, just like for many other aspects of the Japanese life.

> I work in the pharma industry in Japan

I wonder if we've crossed paths in some way before. I also work in the pharma industry (peripherally?).

Maybe we have? :) We should exchange contacts :)

I just realized why your username looks familiar -- we just talked in the Kyoto HN Meetup thread the other day.

Indeed - if you ever come to any HN Kansai event you'll probably see me there :)

How can I get in touch with you?

get on pandoralive.info and hit the "about us" section and there is a contact form there :)

So you will be working hard to make sure that Japan knows that it is depressed, and your pills will solve the problem for them, eh? Sounds honorable, kimosabe.

There's nothing wrong with using pills. I've had severe MDD (clinical depression) since childhood and my mum is the last person who would resort to feeding me pills; they were the only things that were effective enough to let me live my life somewhat normally. They still are.

I tried to substitute them a few times with more exercise, herbs, teas, voodoo, and comedies. I'd be OK for a week or two, but I'd eventually start degrading into a shit state.

Thank the fuck and heavens for the pharmaceutical industry.

First, I don't work on Depression so I can't really answer your comment in any sensible way. I was just sharing my knowledge of the market. Besides, there are conditions where you need treatment. I don't know if you have ever met REAL people suffering from depression but basically when you have that condition you can't function at all anymore. You can't work, you can't have friends, you can't communicate well anymore and when you reach that point I tell you you'd be glad to be able to take some pills to make you a normal person with normal emotions again. Your comment makes me think you don't really know what you are talking about, because depression can lead to suicide and having the right drug at the right time can really save you. I'm not saying the solution is ONLY about drugs, but when you hit the bottom, it's helpful to get back up.

Might be nice if societies didn't develop dependencies on massive, corrupt, for-profit, international pharmaceutical agencies though, wouldn't you think?

While we’re all for disruption here at hacker news, the International Socialist Revolution variant of it seems to not be as popular in these parts.

(Un)fortunately, depending on whether you consider previous implementations the best possible ones or not.

Hey, whatever your -ism, there's still gotta be a Dealer in the addict equation, right? Its not like these things synthesize themselves...

FWIW, fish oil demand is driving overfishing.

http://www.wired.com/science/planetearth/magazine/15-06/st_i...

There are environmentally better sources, thought they are, naturally, not as cheap.

In terms of $/gram of Omega3, flax oil is much, much cheaper than fish oil.

http://www.amazon.com/Barleans-Organic-Oils-Lignan-16-Ounce/...

http://www.barleans.com/images/supplemental/ot-lignan12oz-su...

It also has a lot of 6&9. I'm assuming that still moves you towards a good balance. Can someone tell me I'm mistaken?

flax has a lot of ALA omega 3's, which are less usable than the EPA/DHA in fish oil

I am not an expert, but I've read in many places that the omega-3 in flax oil is far inferior, to the point of almost being worthless, compared with fish oil. IIRC the problem is that flax contains omega-3 in the form of ALA, in contrast to fish oil, which contains EPA and DHA -- the forms we actually need. The body can convert ALA to EPA and DHA, but the conversion process is extremely inefficient (something like only 5% get converted).

"The body can convert ALA to EPA and DHA, but the conversion process is extremely inefficient (something like only 5% get converted."

Interesting. I wonder if that would be practical to do synthetically.

There are companies working on growing omega-3 using algae.

It's already being done. Horizon organic milk has DHA and Omega-3 added from algae products. "While some DHA is derived from fish, we use only plant-based, water-extracted DHA": http://www.horizondairy.com/products/milk-plus-dha-omega-3/w...

I have a fish allergy that makes me a bit nervous to take fish oil. I tried fax seed and stopped after reading about its ineffectiveness. How much milk should I be drinking for the Omega-3 benefits?

Edit: let me be specific. According to the web, each serving of this milk contains 32mg DHA Omega-3. The fish oil recommendation seems to be 3 grams of fish oil. How do these equate?

You have been able to buy it at fancy health food stores for several years now.

You can already buy several different kinds of algae-derived omega-3 DHA supplements on Amazon. But the best deal there is Ovega-3, which at $0.29 per pill is about twice as expensive as fish oil.

You are mistaken. The ration of 6&9 to 3 is what you want to reduce. And as the others have said, ALA is a drastically less useful version of o3.

Now..feeding flax seed to the chickens in your backyard and eating those eggs is an even better (and sustainable) way to get omega 3s.

I am not a fan of flax. Let me suggest walnuts as an alternative. Let me also suggest that consuming less of the "bad" oils is a much more effective preventive measure than eating whatever crap and then trying to supplement with a "good" oil.

Due to the nature of the preferential binding, the 3/6 has to be 1-1 or greater to do >any< good, and since walnuts have a 0.24 : 1 ratio in favour of omega-6s, unfortunately, you wont getting any benefits of omega-3s from walnuts.

Apart from algae sources, the alternatives are a couple of pints of flax seed every night, or going without so many things that you run risk of malnutrition. So, nuts/seeds aren't a solution.

I am curious what your background is/where you get this info? Because that does not fit with my personal firsthand experience with getting well in spite of an incurable inflammatory condition that is supposed to kill me and frequently makes me suicidal if I eat the wrong things (especially the wrong oils).

Thanks for the feedback.

Perhaps you had much worse than a 0.24 : 1 ratio.

Many diets eschew flax seed in general, but something to keep in mind is that unground flax seed itself is a good source of fiber. Mind, I'm not saying it's the best source of EFA's, but it's far better than junk food or fast food. I typically will put a very large spoonful of flax seed into about 3/4cp of Greek yogurt and add a little honey for a tasty treat, but I do also supplement with fish oil pills. I'll also add glazed walnuts to a bowl of plain old oatmeal for a filling and healthy breakfast.

Unfortunately, due to the nature of the 'balance' (preferential binding), anything less than 1-1 in favour of Omega-3 is as useless as nothing. So, something with close to 1-1 ratios, like flax seed won't make any difference unless you eliminate omega-6's from your diet entirely. This isn't just impractical - it's so limiting, you'll have trouble with other nutritional requirements.

I believe that it is certain types of fish oils that are leading over fishing.

For instance if you were to buy salmon oil and the salmon was farmed raised then farmed issues aside you wouldnt be overfishing.

I believe that generic fish oil does lead to overfishing but if you by fish oil from Wild Salmon chances are they arent fishing solely for the oils.

http://www.seafoodwatch.org/cr/SeafoodWatch/web/sfw_factshee...

Farming salmon contributes to overfishing

http://www.bloombergview.com/articles/2014-02-24/your-best-s...

... along with a host of other issues.

And someone once said, "This farmed salmon tastes like cardboard." To which the old fisherman replied, "That is very unfair. There are some palatable cardboards out there."

Farmed salmon doesn't have the useful amounts of omega-3s, since they don't produce actually produce them. Wild salmon eat krill, which eat algae, that are ultimately the source.

Any source on that? Here[1] it says otherwise : "farmed salmon generally has more omega-3s, it is sometimes a more healthful choice than wild."

[1] http://www.washingtonpost.com/lifestyle/food/why-farmed-salm...

I've switched from using fish oil capsules to eating sardines as they are quite high in Omega 3 (around 1g per 3oz), low in mercury, in no danger of overfishing, and relatively cheap.

I've heard good things and I'm seriously starting to consider adding them to my diet, how do you prepare them?

Tinned sardines gently mashed on toast with a splash of Worcestershire sauce or similar.

They're also good with lemon juice on top if you're not a fan of Worcestershire sauce. Or you can melt cheese on top for a variation of the classic tuna-melt.

Also, if you want to avoid the extra omega 6 fatty acids, get the sardines that are packaged in water or olive oil (which is mostly monounsaturated fatty acids) rather than soybean oil.

Add an egg or two and make Fisherman's eggs. (Random google recipe: http://thingsmybellylikes.com/2013/03/25/fishermans-eggs/ ) Super high-protein and IMO tasty. Add some cheese on top for a bit more flavor.

Personally, I just eat them as a snack or light lunch straight from the can. Or perhaps chopped into bits over a salad. Sometimes I even mix them with a little brown rice.

All you need is a few drops of lemon juice.

Mash up with a fork plus half of a raw shallot (diced), optionally a bit of chili powder or black pepper. Spread on toast. Adding some slices of tomato, cucumber, or hard cheese is nice of you have them.

This is one of our fallback lunches/snacks when we haven't made it to the store recently and/or don't have time to cook.

Sardines are also a fantastic source of calcium. They're a super food. And sustainable to boot.

Well, not perfectly sustainable:

http://en.wikipedia.org/wiki/Cannery_Row

There exist other places where sardines are fished other than that one place that overfished.

Right, that's the "perfectly" part.

Seafood watch says they are ok: http://www.montereybayaquarium.org//cr/SeafoodWatch/web/sfw_...

Costco sells Wild Planet brand -- cheap, tasty, and sustainable.

how depressing.

Instead of killing fish, here is my favorite nut mix (BY FAR!), which also happens to be chock full of Omega-3:

http://smile.amazon.com/Planters-Nutrition-Omega-3-Ounce-Can...

Cannot recommend enough. A handful for a snack is filling, healthy and not too caloric.

I can never stop at just a handful though

I dole things like this out to myself each day when I fix my lunch. If I'm going out for lunch I pack it anyways and usually eat it between 10:00-10:30am, keeps me from overeating at lunch. Otherwise, yeah, they'd last about 5 minutes.

Sometimes the simplest idea seems like the best solution. Perhaps not having the entire container in my desk drawer (half open) is not the solution.

Bit too much sugar there for my liking...

So you might want to do some research on ALA, EPA, and DHA. Our ability to convert ALA to Omega-3 is apparently fairly limited. This link appears to be fairly well researched:

http://lpi.oregonstate.edu/infocenter/othernuts/omega3fa/

FYI: Ingredients Walnuts, Sweetened Dried Cranberries (Cranberries, Sugar, Sunflower Oil), Candy Coated Dark Chocolate Soynuts (Dark Chocolate {Sugar, Chocolate, Cocoa Butter}, Sugar, Oil Roasted Soybeans {Soybeans, Soybean Oil}, Artificial Color {Includes Caramel Color}, Corn Syrup, Gum Arabic, Confectioner's Glaze {Carnauba Wax, Beeswax}).

Without doing serious research on every ingredient listed above, let me suggest that you (or other interested readers) can just buy Walnuts for the same effect, without being exposed to all this other crap, which may be a problem for some people. Walnuts are unusually high in omega 3. I have a lot of dietary issues and I would be unlikely to eat the above (and I usually do not eat Planter's because most of their nut mixes are made with peanut oil, which is highly inflammatory and tends to make me psychotic and suicidal).

I cannot take fish oil. I am allergic to shellfish and I break out in hives when I take enough fish oil. So I have long eaten walnuts when I want to bump up my Omega 3 intake. But, for my purposes, a) avoiding problem oils does more for me than trying to specifically counteract them by adding other oils and b) eating less acidly also goes a long way to control my inflammatory condition.

Walnuts have more omega-6 than omega-3, so you're probably not getting any of the effect from it. The two cancel each other out.

The effect might be that eating walnuts fills you up and makes you eat less potato chips. You're right of course, but don't underestimate how bad a place some people are coming from!

http://www.hsph.harvard.edu/nutritionsource/omega-3/

Frank Sacks (Prof. of Cardiovascular Disease Prevention, Dept. of Nutrition)

> There are two major types of omega-3 fatty acids in our diets: One type is alpha-linolenic acid (ALA), which is found in some vegetable oils, such as soybean, rapeseed (canola), and flaxseed, and in walnuts. ALA is also found in some green vegetables, such as Brussels sprouts, kale, spinach, and salad greens. The other type, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is found in fatty fish. The body partially converts ALA to EPA and DHA.

Given that I am supposed to be dead and I have gotten off multiple prescription drugs, my guess is that the approach I am taking is working. Granted, that proves nothing about walnuts per se since I have done a heckuva lot more than just eat walnuts sometimes. (But I also said -- twice -- that I recommend avoiding problem oils and other things as bigger factors.)

Make sure that the nuts you eat are sprouted. I generally try to eat only raw, sprouted, organic nuts, but they are expensive...

What's the advantage of sprouted nuts?

Too much sugar and processed seed oils (e.g. sunflower and soybean).

IIRC, you need a 1/5 (Omega 3 / Omega 6) ratio, but our usual diet is so poor in the former that we end up deprived.

Palm oil, which is everywhere, has Omega 6 aplenty, and (virtually?) no Omega 3. In Europe, it is usually listed as "vegetal oil" in the ingredients lists. When it's not palm, they put the full name.

palm oil is only 9% polyunsaturated, as opposed to something like canola which is 20%.

I had never heard of canola oil.

The ratio is ~1/2, which is pretty good to know.

> I had never heard of canola oil.

It is called different things in different places. Canola is actually a specific cultivar of Rapeseed. Canola actually stands for "Canada Oil" and the term probably isn't well known out of North America.

http://en.wikipedia.org/wiki/Canola

http://en.wikipedia.org/wiki/Rapeseed

South America, canola oil is pretty well known

Please be aware of the issue of rancidity before taking any fish oil supplements.

http://blog.omega3innovations.com/blog/bid/215649/Is-Your-Fi...

There's an obvious conflict of interest with that link. They discuss the rancidity of fish oil and then pitch their own fish oil product. I've heard rancidity of fish oil discussed before. It seems like a reasonable thing to be concerned with, but I'd like to see an impartial, scientific discussion.

I like Coromega brand because it can't become rancid. The oil is sealed in an air tight packet until you consume it.

Open a capsule of each new batch and smell it. Then put the package in the fridge, and keep it there. Problem solved.

The fridge alleviates many such issues.

I've had fish oil capsules that were packaged under nitrogen, specifically to reduce degradation before sale. But those are not cheap.

Grass fed beef is apparently also a good source of Omega-3

http://www.ncbi.nlm.nih.gov/pubmed/16500874

Brazilian meat is grass fed. Which countries more export grass fed meat?

New Zealand exclusively produces grass-fed beef.

I don't know about countries exporting grass fed meat, but in the US there is a growing movement for raising grass-fed cattle and pastured chickens (for meat and eggs) usually within 100 miles of major cities, as opposed to grain-fed livestock raised in large factory farms.

The Omega 3 to 6 ratios of the resulting meat (and eggs) is better than the grain-fed ones. It seems that a lot of these inflammation problems are not only caused by the diet of the average person but also caused by the diet of the average livestock that we're consuming.

They cut down the rainforest to create those pastures which the cows graze on.

There is recent research linking fish oil and prostate cancer, especially more aggressive forms of prostate cancer.

http://www.nlm.nih.gov/medlineplus/podcast/transcript090313....

I was going to link that too if someone else didn't. But since the base rate is already about 150/100,000 per year, and 15% over a lifetime, and the survivability for prostate cancer is high, the increase isn't really that much and the benefits outweigh the risks for me.

The great majority of effects tested and listed in the 'Human Effect Matrix' at [2] are either minor in magnitude or non-existent. That would seem to contradict your statement that Omega-3 is a miracle chemical.

Am I reading it wrong?

This is reads as "minor or nonexistent?

  Evidence Level  Effect      Change    Magnitude  Consensus
  A               Depression  Decrease  Notable    100%

No, and I didn't say it did.

The parent to my original comment claimed that Omega-3 is a "wonder chemical", having many beneficial effects, and cited that website as evidence. I was responding to that claim by pointing out that the website does not in fact appear to back up their position.

The problem is you expanded OP's claim. For starters OP never used your interpretation of wonder chemical: "cures many ailments". The article was on depression and OP never broadened the "therapeutic horizon." The linked website did not describe the effects of fish oil on depression as "minor in magnitude or non-existent."

I think we disagree on the interpretation of

> Score another point for fish oil supplementation, on top of the already enormous pile of scientific research showing it to be a miracle chemical (and I definitely don't say that lightly) [2].

I read that as "here is yet another thing that omega-3 treats", rather than "here is yet more evidence that omega-3 treats depression". Especially since it followed a quote from the article about anti-inflammatory properties rather than specifically mentioning depression.

Followed by:

> Seriously, if you aren't getting enough omega 3 fatty acids, [...], you're seriously missing out on some good stuff. Among supplement enthusiasts, it's consistently declared to be one of the only supplements that's actually useful.

Among supplement enthusiasts, not among depression sufferers.

But then it can be so easy to misunderstand the written word; perhaps I missed the intent of the original comment.

There is good evidence that supplementing fish oil does nothing to prevent death, but that eating fish does.

I haven't got cites but it was pretty clear on this BBC Radio Four programme - maybe someone else has got better sources?

http://www.bbc.co.uk/programmes/b019dl1b

(They talk about the dangers of Selenium supplementation in regions with plenty of bioavailable selenium in the soil, especially when combined with Vit E supplementation. These are not heroic doses either.)

Why do you prefer the liquid form?

I think Andrew Weil's books are a good common sense source on supplements and he recommends fish oils purified to exclude mercury and PCB's. For counterexamples, I've noticed a few people taking quite large dosages of B complex vitamins. Dr. Weil notes that mega doses of B3 and B6 can cause problems including irreversible nerve damage. He also recommends against resveratrol supplements, another trendy thing.

The Cochrane review on omega-3 fats in 2004[1] didn't find any clear benefit concerning Mortality/Cardiovascular problems/Cancer.

[1] http://summaries.cochrane.org/CD003177/there-is-not-enough-e...

Follow-up studies, such as this 12,000 person RCT [1], have not been any more favorable towards omega-3 fatty acids.

When my patients ask me if they should take omega-3 capsules, I tell them that it depends on whether they enjoy paying for them. (Some do.)

1 = http://www.nejm.org/doi/full/10.1056/NEJMoa1205409

"on top of the already enormous pile of scientific research showing it to be a miracle chemical (and I definitely don't say that lightly)"

http://www.badscience.net/category/fish-oil/

The research hasn't held up, but the marketing and supplement industry pretends as if it has.

Also hemp hearts - available from some costco stores and most whole foods are an excellent source of omega 3s. They are good in smoothies too.

Fish oil supplementation is, like most other supplementation, really only applauded by the supplement industry.

There's no proof any of it does much, which is why here in the UK all supplement advertising has to include disclaimers like "May benefit the elderly or those on a restricted diet"

There have been some decent clinical trials showing a high does of fish oil (something like 1g a day) improves mood better than placebo in bipolar depresssives. There are some risks to taking really high doses of fish oil every day though - and not just mercury content.

Similar trials for just doing plenty of regular excersise such as walking show a better result. Given that excersise is really good for you, it's probably a better option.

try flax, not fish.

It took me a while to slog through that whole long list of references at the end of the end of the article, but correlational study designs don't impress more by being numerous, especially when most of them are published in middling-to-lousy journals. That's what isn't fun about reading about medical issues here on Hacker News: too many of the articles kindly submitted here are of much too low quality to be worthy of our attention. There are some intriguing ideas in this opinion piece, but basically hardly anything there is backed up by experimental studies, not in a human study and not even in an animal study. The title of the article reflects an attempt to come up with a One True Cause of depression that surely is not the one true cause (most doctors who are experts in depression, or in inflammation, do NOT characterize depression as an "inflammatory disease") and then the article goes off the rails from there.

Check back when there is better established evidence about treatment. A better read about depression by a more informed physician would be a book review submitted recently to HN[1] that was hardly noticed when it was submitted.

[1] http://www.sciencebasedmedicine.org/depression-re-examined-a...

You can check your inflammation levels via a blood test called hs-CRP (http://en.wikipedia.org/wiki/C-reactive_protein).

I took it and was surprised to learn I was in the high risk range. I tried a vegetarian diet for just under a month, re-tested and I'd dropped into the low risk range (this was the only lifestyle change I made that month). I found that a full vegetarian diet isn't sustainable for me so now I'm trying out only having meat once a day (usually for dinner) and will re-test to see what result that has. I suspect that the absence of meat may have been less important than the increase in vegetables.

The caveat is that hs-CRP isn't a perfect test because your result can be spiked temporarily if e.g. your body is recovering from intense exercise or a cold. That's why I think it's a good test to do more regularly and have longitudinal data for.

I've been spending a bunch of time getting more comprehensive blood tests recently. If you've any questions feel free to ping me (harjeet [dot] taggar [at] gmail).

Very interesting; where do you get your blood tested? AFAIK, you have to be willing to pay the lab expense, which is tailored for insurance.

Yes unfortunately most insurance won't cover any tests beyond the basic ones in your yearly medical. There are a few options:

- WellnessFX (http://wellnessfx.com) offers the nicest experience and display of your results, but it's pricey and the tests all come bundled together so you can't pick just one or two you're interested in.

- http://health-tests-direct.com and http://directlabs.com are other options that have more a la carte options.

- If you're in the Bay Area, the cheapest (by some distance) option is to use a new blood testing lab called Theranos, which has a location in the back of the Walgreens on University Ave in Palo Alto. If you download their lab order form (http://theranos.com/Content/pdf/theranos_lab_form.pdf), tick the tests you'd like and have an MD sign it (doesn't have to be your doctor, could be a friend). You can take it into the Walgreens and they'll draw your blood there and email you the results a few days later.

Here is a nice fluff piece on the founder of Theranos

http://www.wired.com/wiredscience/2014/02/elizabeth-holmes-t...

Url being wired.com already make it very clear it's a fluff piece

I'm very curious that eating meat only once a day is a compromise for you. How much did you eat before you started thinking about this?

At a minimum twice a day, which I don't think is that unusual for most people e.g a chicken sandwich for lunch and chicken with some kind of side for dinner.

Cutting down to once a day i.e. having a vegetarian lunch, might not sound like much but it's harder than you'd expect. Most restaurant versions of a vegetarian option is a meat dish minus the meat e.g. a sandwich with just lettuce and perhaps one tomato slice. Finding a vegetarian option that's tasty and filling can be challenging (though comes with a good consequence of forcing you to discover new places to eat).

I'm sure this is much easier if you work someplace with a good catered lunch option.

Hmmm, I guess I'm something of an anomaly then. I can easily skip meat for a few days, or weeks, depending on what I'm cooking. I essentially never eat meat for breakfast, and my lunches normally don't involve meat either (typically a peanut butter and banana sandwich on wheat, some carrots with hummus, and a yogurt). If I eat at work, I prefer to make a salad. Dinner's the most likely culprit, although there are a lot of curries I enjoy vegetarian. Now that I think about it, I guess the last time I ate meat was Saturday, and someone else made the meal.

I guess it depends on how much you cook too, you're right about it being harder to find good vegetarian options, but I eat out one meal a week at most normally, and prefer none because I love cooking. I live in a small-midsize town in the south, so there's plenty of meat about.

For a counter-point, I eat an extremely meat heavy diet and have a superb CRP number (.23).

It's more likely about avoiding low quality meats, which unfortunately is what 95% of the meat produced in the US is.

That's a very good point. Quality of meat isn't something that seems to be accounted for in studies linking meat consumption to various diseases/health issues.

Out of curiousity, do you eat a lot of vegetables?

Estimating here but I'd put my breakdown by calorie as:

-45% high quality meat (grassfed, pastured, cage-free depending on species)

-10% low quality meat (traditional supermarket stuff)

-30% green leafy vegetables (read: very low non-dietary-fiber carbs)

-10% fruit or carby veggies (e.g. tubers)

-5% grains (never gluten containing)

So I definitely have other confounding factors that might influence my CRP number: low carbs, very low grains. That said, I arrived at my current diet via 3.5 years of A/B testing what works for me, optimizing for specifically what causes my digestion the least inflammation. I'm very happy with the results.

By low quality meat, do you just mean corn fed?

For ruminants, yes.

But I think "just" might be understating it. Corn-fed cattle do not have the proper stomach ph to naturally protect against bacteria overgrowth in their stomachs (whereas if they consumed solely grass, this is naturally not a problem). As a workaround to the bacteria problem they are force fed antibiotics for their entire lives. Additionally: corn fed cattle yield 30-50% more meat because they are insanely obese. Beef producers have a perverse incentive to keep these animals in confined conditions (read: knee deep in their own shit) so that they don't get too much exercise. When you eat conventionally raised cattle, you're consuming the meat of a crippling infirm animal that lived its life in appalling conditions. It's a bad scene.

It's not just ruminants; these days even farmed fish are fed corn.

Is there any evidence that eating corn-fed as opposed to grass-fed ruminants affects health in any way?

For anyone else that was wondering how much this test will run you-

"Cost is just $40 – $70 and it’s covered by most insurers, including Medicare..."[0]

[0]http://www.forbes.com/sites/melaniehaiken/2011/06/17/3-lifes...

Recent articles have tied omega 3 intake to increased risk of prostate cancer. Got a lot of press last year. I took Omega 3 for the last 14 years. Spent thousands buying Nordic Naturals from Whole Foods at $25/bottle. Whenever I'd stop taking it, I felt a decline in mood so thought it had good systemic benefits. When I went off it this time, I felt zero change before or after (haven't taken since last summer).

This study was the last straw. I'd already given up supplements and even a daily multivitamin as studies indicate no positive effect and possible harm. Now I take no supplements. The more I read the more I'm convinced it's faulty science and marketing. A healthy, varied diet of mainly plant based foods should provide all that most people need. If you look at links to omega 3 studies on Wikipedia I don't recall there being conclusive positive evidence, but maybe I'm wrong. Couple of links on prostate cancer study and whether it's accurate or not:

http://www.cancer.org/cancer/news/omega-3-fatty-acids-linked...

http://health.heraldtribune.com/2013/08/26/dr-oz-omega-3-can...

http://articles.mercola.com/sites/articles/archive/2013/07/3...

Still, some vitamins may be worth supplementing depending upon your diet, exposure to sun, and activity level. For example:

http://examine.com/supplements/Vitamin+D/

http://examine.com/supplements/Magnesium/

http://examine.com/supplements/Vitamin+K/

Is there an effective way to know which vitamins you're missing? Can full blood tests help tell you which vitamins you should be taking daily?

It would be so fantastic if we could just have a chip implanted to continuously measure this stuff, then download it and analyze on a daily, weekly, monthly and annual basis. There's so much cool science to be done here, especially if this is done on a global scale.

Yes. There are common panels available at Quest/Labcorp that will measure critical nutrients such as Vitamin D or Vitamin B12. In addition, there is a more comprehensive test called ION available from Metametrix.

Examine.com is a great website. In general, I would consider Vitamin D and Magnesium to be the most beneficial for a layperson without any specific health issues.

There are problems with taking high doses of Vitamin D3 that may be an allergic reaction or genetic, and controversy that the amount of non-supplement D3 consumed by people on average may be a lot higher than we think.

http://www.mgwater.com/vitamin_d.shtml http://www.livestrong.com/article/302715-risks-of-too-much-v...

(result of random refference googling)

There were some well-reported flaws in that multivitamin study. One I remember off the top of my head from the study done with cardiovascular patients was that the "high levels" of vitamin D3 given to the participants was 100 IU.

Edit with one quick link.

http://oregonstate.edu/ua/ncs/archives/2013/dec/review-most-...

Your link to the Herald Tribune and Mercola both recommend DHA (and omega-3). It is seriously one of the greatest things you can take, hands down. Nordic Natural is an expensive brand, and buying at Whole Foods is even more expensive (try Amazon, and a cheaper, but quality brand is Carlson's). It is hard to tell sometimes when you go off a supplement the true effects because your high DHA levels can take a while to be used up, and even then the body has processes to try and scavenge or breakdown molecules in other areas to make up for it. It is much more efficient and beneficial to provide the needed stuff in a useable form.

Mercola is certainly not a credible source

Most of his health advice is pretty solid, it's just that many of his products are scams.

Frankly, if he sells scamming products then his health advise is worthless.

Why? I'd certainly take everything he says cum grano salis, but it's still better than pretty much any other general health information site on the web.

You can practically set your watch by the timing of the latest meme that purports to identify the One True Panacea for Clinical Depression™. Looking like it'll be time to pull the crown on mine pretty soon.

The link between depression and inflammation is news to me. Is it fully accepted, or still being worked on? I've had bad run-ins with both, sometimes, at the same time. A particular case was a bad burnout incident I endured a few years ago. I saw many doctors trying to figure out why my hands and wrists had enormous amounts of tension. MRIs, x-rays, and conduction tests showed no issues. I had to leave my job and rest for several months entirely to be able to use them again.

Because of this, I've always suspected a stronger mind-body link than traditional Western medicine currently admits to (obvious caveat of n = 1). It seems that whatever state my mind is in, my body follows soon after. Mental anxiety begets physical tension. It's like my whole body downclocks itself to deal with things.

The mind will get it's way, no matter how much you resist.

>Because of this, I've always suspected a stronger mind-body link than traditional Western medicine currently admits to (obvious caveat of n = 1). It seems that whatever state my mind is in, my body follows soon after. Mental anxiety begets physical tension. It's like my whole body downclocks itself to deal with things.

Um every western medical practitioner "admits" to this kind of mind body connection.

I think western medicine is pretty on board with the notion that significant stress causes (or exacerbates) other issues.

As just one random example:

http://www.webmd.com/mental-health/effects-of-stress-on-your...

Yeah, but no doctors asked about my stress, or emotional health, or anything that could have started me down the line of investigation. I treated it as an isolated physical problem, not a symptom of stress/mental issues. The response was always the same: "we don't know...sorry."

Maybe I should've realized that stress was killing me, but I was severely depressed. It's not like I could see myself objectively.

I think the problem is that many patients prefer the idea that they have a physical illness, so some doctors don't even consider emotional causes. Also, doctors simply don't have the time needed to deal with these kinds of issues.

Yeah, I imagine most good doctors know full well it's emotional/stress, but avoid telling the patients because it's not what patients like to hear, or they don't think it'll be helpful.

Pharmaceutical treatments for stress have some harmful side effects, whereas just sending them away with "don't worry about it" and a lollipop might go a good way to alleviating some of it.

That's because popular culture believes that there's a separation, which means that if a doctor of your physical health asks you about your emotional well-being, the typical response isn't, "Gee, he must need some relevant information" but rather "Oh, my doctor is being inappropriate; maybe I ought to get offended and sue".

> Yeah, but no doctors asked about my stress, or emotional health, or anything that could have started me down the line of investigation.

That's pretty shocking. Even a family GP should be asking about that stuff. I've never had one not. When I had GI issues the specialist I saw went as far as to say "We're going to do more tests, but I can explain all your symptoms with physical response to stress." Ended up being a stomach ulcer.

There are quite a few physical conditions that are commonly accepted to be largely psychosomatic in origin, including things like osteoarthritis. While it's probably true that the term translates to "it's all in your head" to most folks, a better translation is probably "it's mostly from your head". Stress and tension aren't just metaphorical; they're usually accompanied by actual physical/mechanical manifestations that can sometimes have a devastating and irreversible effect on joints, tendons and other assorted bits of framing, machinery and plumbing. (It shouldn't be surprising to find that the discomfort and dysfunction feed back into the emotional state, compounding the problem.) And that's just from long-term, low-level stuff that people tend to try to ignore. I can't recall running across a physician with any real experience (interns are another matter) who hasn't had a solid grasp of that concept.

Some premises of this article are at least sound, at least, fishy. Easy language, lot of promises, and a lot of plausible things but not necessarily with causal relation.

It starts with "We now know that depression is associated with [...]", where AFAIK we are far from pinning down etiology of depression (there may be multiple mechanisms, etc). And it is one of reasons why antidepressant have relatively low effectiveness. The abstract ends with a longer list of things that make it flashy.

Moreover, things like smoking are sometimes considered actually having mildly anti-depressive effect (though it is disputed).

I don't say that the paper is wrong. Just a paper not listing doubts and promising a lot should be less believed that one making very humble observations (but the later one would not make HN frontpage, hence the bias).

Can anyone acquainted with the hard sciences comment on whether this paper passes even a basic sniff test? The title of the paper and so many references to other psychiatry journals seem like potential red flags.

I saw some red flags as well (see my comment), so I asked a question:

http://cogsci.stackexchange.com/questions/5841/is-it-univers...

Are you saying you find it... fishy?

It seems to be mostly wishful thinking...see my other comment here.

Inflammation in the body has been correlated with a lot of diseases believe it or not. Gluten is one of the big contributors to inflammation in the body. A lot of people laugh at the whole "Gluten Free" thing, but there's a good bit of evidence that significantly reducing or removing it from your diet can make a serious impact.

Could you point me to the "good bit of evidence" that shows this?

Less than 2 years ago, my wife was diagnosed with MS (Multiple sclerosis). As soon as we found out, I started digging like crazy to learn more about why this happened and what we could do to prevent it from progressing. I'm a big believer in that the body has the ability to heal itself by avoiding certain foods and intaking others. I mean, food is fuel we put in our body.

After digging for a while, I came upon some staggering discoveries. First, there are people who have reversed their MS almost completely on diet alone. The diets consist of A LOT of high-nutrition fruits and vegetables along with Omega 3's, organic meats, etc. These Paleo-like diets also forbid gluten with the main reason being that it causes serious inflammation in some folks. This TEDx video by Dr. Terry Wahl was very helpful (http://www.youtube.com/watch?v=KLjgBLwH3Wc). I read her book and it literally laid the foundation for which changed our eating habits entirely.

A month or so after, we flew out to Massachusetts to a well-known wellness center where they performed various blood and stool tests. The Dr's (including a Nutritionist) sat down with us for the entire day and asked about daily habits from what our work days were like to what we ate. Without mentioning my own research, they also said that gluten is something we should completely remove from our diet.

There's a ton of other stuff out there, but since removing gluten entirely, my wife has felt great. We just did an MRI and she has no new lesions. She no longer experiences blurriness or weakness which is great. It may not be completely because of Gluten, but removing seems to have seriously made a impact.

All of this seems to be anecdotal. Do you know of any research (as in, studies) which support any of this?

Google returned this:

http://www.ncbi.nlm.nih.gov/pubmed/19758171

and a quasi-bibliography:

http://www.celiac.com/articles/124/1/Multiple-Sclerosis-and-...

I love that anecdotes are considered worthless in medicine when in fact they're very clearly good places to start.

Take an anecdote and do a small population study to try and find correlation. Then if there are any significant results, start looking for causation.

In history nothing is legit except for primary sources. In medicine, it seems, primary sources -- no matter how compelling -- are worth a damn. Hilarious.

> I love that anecdotes are considered worthless in medicine when in fact they're very clearly good places to start.

They're a great place to start for a scientist with training in conducting medical research and the resources to carry it out.

They're a terrible place to start for an internet forum reader who has neither.

No. Medicine is so broad and subjective that it's easy to find an anecdote implying almost anything. That's why expensive double blind is so important -- even doctors fool themselves.

How many "carrots cured my cancer" wild goose chases would it take to bankrupt even the biggest company? Whatever that number is, it's smaller than the number of wild-ass medical anecdotes rolling around out there.

Of course, everybody thinks that their own anecdote is compelling and obvious and all their friends on carb-free diets are idiots...

Because isolated anecdotes aren't necessarily the same thing as "medicine".

I'm diagnosed since 3 years and have a similar (in some ways) story.

I've removed Gluten and all Dairy, all due to advice from my parent who was frenetic in researching prior studies, books, anecdotes etc.

I've certainly been depressed for a long time, but I'm making recovery.

Well, it quite well known that gluten creates several problems for SOME people. That's quite a different argument from the over generalization you did at the GP.

It's indeed something to keep in mind, but the good news is that it's easy to test for.

Gluten intolerance isn't a binary state, it's a scale. Everyone's on it somewhere, but unless it's REALLY bad, you'd probably never get diagnosed or even tested.

Main benefit of avoiding gluten though is it's a simple rule that helps you avoid a lot of bad foods, and excuse it socially.

http://www.celiaccentral.org/research-news/

My wife has celiac disease, which is basically a gluten allergy. Her grandfather had sprue, which was renamed to celiac more commonly[1].

As much as I hate anecdotal evidence, I personally do feel significantly better on a day to day basis when I eliminate the most hefty forms of gluten (bread, for instance). Could have absolutely nothing to do with it, but it seems to hold even when I eat gluten free substitutes. Again, an anecdote, but look into celiac for more solid research on the subject.

[1]http://www.nlm.nih.gov/medlineplus/ency/article/000233.htm

Even if you particularly feel better, that's not evidence that gluten is "bad" in every way that's being claimed here.

http://www.ncbi.nlm.nih.gov/pubmed/18404144

Can't wait to read this. As a person who has dealt with severe depression, and has come through it alive, I'm always interested in new research on the subject.

Same. From what I've read so far (only partially through the paper) a lot of this is what we already know, but with more evidence for the claims. Really helpful for those of us who continue to combat depression on a regular basis.

Actually, I think you might be better looking elsewhere for help with depression. In my own experience, and that of other people I know, psychological factors have always been the main cause of depression, and resolving them results in curing the depression. The problem is that it isn't always easy to identify the factors causing the depression.

As for the science: we do know that both psychological stressors and infections both cause inflammation. Stress results in activation of the HPA axis and sympathetic nervous system, which screws up the immune system in various ways (including inflammation). Conversely, having a severe infection can make you feel depressed.

It's really just a theory that inflammation causes depression. I think it's more likely that it's a result of cortisol and/or neurotransmitters (i.e. too much brain activity). Cortisol seems a more likely candidate for being central to depression in my opinion.

The science here seems to be based on a desire to have a physical rather than a psychological cause for depression. Michael Maes has a history of that (see his CFS publications).

It's legitimate to use a chemical response as a short-term solution, if it's safe and non-addictive. This walks straight into the "every case is different" territory, though.

Seems like taking action in the real world and avoiding sources of inflammation would have a positive psychological effect. Giving the person a feeling of control over one area of their life.

Surely that would be beneficial, whether or not the link between depression and inflammation is scientifically proven?

Sure, anything can be a placebo effect. However I myself prefer to understand exactly what is happening rather than believing fairy stories, and I think it's fairer to patients as well.

Unfortunately there is a lot of dubious science out there, and a lot of patients who prefer the fairy stories.

Having said that, doing things like exercising and having a good diet will certainly improve health. Exercise has proven to be very beneficial for depression, although I don't think that inflammation has been proven to be what mediates the effect.

Pretty fascinating, I didn't realize there were any links between depression and inflammation. In addition to suffering from depression starting at a fairly young age, I also have allergic reactions that result in inflammatory responses to seemingly random environmental factors. This is something that appears to run in the family. I wonder if addressing the allergic symptom would suppress some of the depressive ones?

A diet described in a book titled "Perfect Health Diet" has been reported to help with allergies.

I've suffered quite a lot from inflammatory responses to food (especially gluten and casein) and had mental symptoms similar to depression (not clinical though). Water retention, pain, weakness, the whole lot. It took some years until I made the connection and have since stayed on a gluten- and casein-free diet, adding fish oil and apple cider vinegar. I lost > 30 pounds since (inflammation seems to cancel out weight loss) and feel great mentally (most of the time). Whenever I have a setback, I become irritable and depressive - usually quickly revertable by two fish oil capsules and a glass of diluted ACV (moodiness disappears within 2 hours; water retention takes 1-2 days to disappear again - this seems to be associated with the lymphatic system).

Interesting, just the other day I was listening to Joe Rogan's podcast with Dr.Rhonda Patrick (#459). If I recall correctly, they breifly discuss inflammation. She goes on to mention that elevated levels of "C-reactive protein" in the blood is used as a marker for inflammation. The podcast is worth a listen, they go into other topics such as nutrition, vitamins & minerals, etc. http://podcasts.joerogan.net/podcasts/dr-rhonda-patrick

I suspect there may be some posts here dismissing a lot of this as obvious - but it's actually really interesting to hear further evidence that a lot of lifestyle factors really do play a large role as we thought.

The best part about things like this is that, as they say, they're amenable to change - you can affect them, so you can reduce the severity of the feedback loop that makes depression so insidious.

If a lot of depression's hows/whats/whys were "obvious" this article would not be included in the journal's "Current Controversies in Psychiatry."[^1]

[^1]: https://www.biomedcentral.com/bmcmed/series/CCP

Why is there an assumption that the inflammation comes from anything other than the mind state of depression itself?

http://www.sciencebasedmedicine.org/depression-re-examined-a...

That study is interesting, but doesn't mention inflammation. It basically says that depression is a result of stress.

Exactly. Then maybe the order is stress -> depression -> inflammation.

I think that is likely. Or perhaps depression and inflammation are both a result of stress (through HPA axis and SNS activation).

I guess my original point is that they're trying to look for the mechanism of the inflammation because they assume that by solving the inflammation that the depression will be solved, whereas it could be that the inflammation is a protective reaction against depression the same way that it is a in large part a protective reaction against other forms of illness.

direct link: http://www.biomedcentral.com/1741-7015/11/200

This is actually a fascinating paper. Keep reading until you see the connection between inflammation, exercise and depression... Wow!

I have a conjecture about depression. I believe that autoimmune conditions (e.g. hypothyroidism, MS, vitamin D deficiency) are sometimes a result of the self-hate associated with severe bouts of depression. The individual feels adversely about their existence, and so the body sets about deconstructing itself. I would be very happy to learn this is never the case, but I suspect that it sometimes is the case. (see: https://en.wikipedia.org/wiki/Nocebo )

I suffer from depression for more than 20 years. Here is what should be done to fight it effectively :

- take anti-depressants - wake up every day early and at the same time (6 AM from Monday to Sunday) - when there is not enough sun outside, sit 30 minutes in front of a full specter lamp - eat healthy (vegetables & fish oil) - have some physical activity (walking, standing desk) - socialize

If I was able to effectively do the last 3 things I think depression would have no impact in my life.

I'll bet this new empirical scientific result will make psychiatrists and psychologists abandon talk therapy and their questionable anti-depression drugs, right away, in the public interest. Let's all hold our breath for that outcome.

http://www.planet-science.com/media/24009/holding%20breath_9...

I'm curious: does this imply that plain-old non-specific anti-inflammatory drugs combat depression? I'm aware that sleep-deprivation, cold-caps, and, oddly-enough, ketamine all have anti-depressant effects, and that these are mostly unexplained—would the link here be that these things have anti-inflammatory effects on the brain?

Except apparently they do the opposite.

http://www.sciencedaily.com/releases/2011/04/110425153602.ht...

>Except apparently they do the opposite.

Welcome to every debate on nutrition, supplements, and pharmaceuticals in history.

Regardless, the study you linked says they reduce the effectiveness of SSRIs, not that they exacerbate depression.

I suffer from depression and a grab bag of auto-immune/inflammatory conditions.

The drug that seems to have the biggest impact upon my depression is Etanercept despite it being primarily to treat my arthritis etc,

Ketamine would be cheaper. hell, heroin would be cheaper.

Ketamine is actually quite effective

http://ajp.psychiatryonline.org/article.aspx?articleid=17333...

> does this imply that plain-old non-specific anti-inflammatory drugs combat depression?

Yes, but taking them doesn't solve the underlying problem, and they're not safe to take on a daily basis. If you were going to use an anti-inflammatory though then CBD or THCA would probably be better than, say, ibuprofen.

This would be a very interesting area for future research. Those drugs that you mentioned are not commonly linked with anti-inflammatory activity - feels more likely that it would be linked to more directly psychoactive properties. Anecdotally, I believe that anti-inflammatories such as NSAIDs (non-steroidal anti-inflammatory drugs, i.e. Ibuprofen and Naproxen Sodium) and Minocycline have been cited as having anti-depressant impacts. Minocycline is a very potent anti-inflammatory and has been used off-label in a variety of autoimmune conditions.

Some further reading - http://www.ncbi.nlm.nih.gov/pubmed/18267354 http://www2.kenes.com/wcap/scientific/Documents/Symposia/Tsu...

Look I'll just say it. This strongly matches the pattern of all the other hiding-in-plain-sight, simplistic explanations for complex bio-existential problems, that turn out to be bullshit.

Yet, nearly all breakthroughs in medicine seem to follow that same pattern, at least for me, an outsider.

I can't throw it away that easily, and by the way you phrase your comment, I think you can't either. Yes, the fact that it is in the oppinion column isn't a good indicator... I'm in the "waitting further results" mode.

"Yet, nearly all breakthroughs in medicine seem to follow that same pattern, at least for me, an outsider."

Yes, the pattern of selection bias.

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