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Brain's Dumped DNA May Lead to Stress, Depression (scientificamerican.com)
161 points by extarial on Sept 14, 2018 | hide | past | favorite | 42 comments



None of this is really that new, and I wish this article was longer, because apparently not a lot of people know about any of this.

It is already known that a wide range of disorders, inside and outside of the brain, are linked to inflammation and also should be categorized as mitochondrial disorders.

Unfortunately, when these two are put together, you end up with an inability for doctors to tell patients they have an inflammation problem: all the tests say negative (I've even met people where this is true, yet they clearly have obvious symptoms of it). However, when you put the patients on a strict anti-inflammation diet and lifestyle, the symptoms go away, as if by magic (and since doctors never recommend regimes that work, patients themselves have to go out and do it themselves; without proper guidance, this has mixed results).

That said, surprisingly common advice works for a wide range of people: avoid foods that interfere with your body's ability to engage autophagy (such as grains and sugars; for some people this means a strict but clean keto diet), regular one-meal-a-day intermittent fasting (helps maintain a state of regular autophagy), stop being overweight (the first two help a lot with this), regular sleep cycles and enough sleep (the previous three help with this), and regular exercise (HIIT is most effective for the results required to prolong life; and all the previous suggestions free up time and energy to fit this into your lifestyle, where for many, it wouldn't have fit before).

I've never seen a doctor in the field ever recommend any of these, yet the past decade of science has been entirely focused on these because of how effective they are to treat common (and dangerous) diseases. There is a disconnect between what we know and what is practiced.


> I've never seen a doctor in the field ever recommend any of these, [...]. There is a disconnect between what we know and what is practiced.

The disconnect has been present since the 1800's (ref: Mad in America [0]), where the Quakers got much better results in their Asylums [1] than the medical asylums. The Quakers were pushed out of the asylum business by doctors, who by the early 1900's thought their patients benefited from getting lobotomized and electrocuted.

2 days ago I saw this article from 15 years ago in /newest:

Diseases of the Mind (2003) (newsweek.com) - https://news.ycombinator.com/item?id=17975716

Someone noticed a link between cortisol and psychosis in the 1950's. Scientists have known since the 1970's that so-called "mental" problems are related to the metabolism, that stress impairs the metabolism, and that "mental" problems resolve with appropriate metabolic interventions. Infections are a type of stress - I think emotional stress is a more important factor for most such patients than actual infections.

[0] https://books.google.com/books?isbn=0465020143 [1] http://qmh.haverford.edu/


But the keto diet is a fad and very dangerous diet, with lots of research and education having taught our doctors the state of ketosis is dangerous and extreme for our bodies. And that the term is associated with severe insulin failure, i.e. it will never be sustainable. Basically you need glucose from external sources to survive and shouldn't forget mama and papa food company or pharmaceutical x when thinking of your solution


Keto was created specifically for people with epilepsy. It works wonders for a subset of those patients, and for them any potential down sides are very much worth it. Some people with migraine (which in some ways resembles epilepsy) have also noticed a reduction of frequency and severity of attacks.

Parts of the two groups mentioned above have been on keto since the 1930s. A diet that's about a century old can't really be categorized as a fad. And while there have been oodles of studies highlighting the dangers of the western diet, which is killing millions, I haven't seen the same for keto.

Of course, there are many confounding factors here. But it's indisputable that keto works in improving epilepsy sufferers' lives.


I think you might be conflating ketosis with ketoacidosis. Very different things.


I believe parent was sarcastic, as in “keto is not sustainable because it would impact the profits of X and Y, please do something else”


Loads of people have been on keto for years without dropping dead. Carbs aren't absolutely necessary.


>> Carbs aren't absolutely necessary.

My personal experience says otherwise. Whenever I have tried to reduce carbohydrate intake my system goes haywire. I suffer constipation, body aches, overall weakness in body during night while sleeping, I sleep worse. I workout every day and I have realized carbs are extremely important (even though I try to take plenty of protein). When I resume carbs most of the problems I cited above, go away.


That's keto-flu. Everyone experiences it when they first start keto.

Supplement with electrolytes.

And eating too many grams of protein causes gluconeogenesis.


As my sibling comment says there's something called keto flu. Have you tried sticking to strict low carb for approximately two weeks or more?

I personally have no problems with a keto diet, and I feel much better and less bloated. But people respond differently to it. If you feel it doesn't work for you, don't do keto.


To follow up on this, the reason is that excess protein is converted to carbohydrates in the body. It’s more expensive, and takes work to eliminate urea derivatives, but as long as someone is getting enough protein, they will be okay. There are risks to having too many saturated or polyunsaturated fats, but those risks aren’t inherent in low carb dieting.


I don't know whether keto is ultimately good or bad but this isn't a very good argument.

People do tons of things that are unhealthy but don't lead to immediate death. Loads of people smoke for years without dropping dead as well.


When I google "anti-inflammatory diet" I see recommendations to eat whole grains. Can you explain the contradiction with your recommendation?


I read something recently that a doctor researching causes of treatment resistant depression found there were metabolic abnormalities that show up in cerebrospinal fluid but not in blood tests. Unfortunately, blood tests are easier, so that's what is done.


I'm curious about HIIT - do you have any links on hand that you could share?


The Wikipedia page for HIIT is quite informative.

More than 10 years ago I did HIIT for running. After warm up (20 km walk to the running path) I started with walking 2-3 minutes and then running as fast as I could for 30 seconds. The first times felt like I would die. It was hard to breathe, and a lot of pollen in the air did not help.

The walk and run is 1 cycle. When beginning the training, the cycles start at a low number of repetitions (1-2). The repetitions increase every time when training. So if on Monday I did 4 cycles on Wednesday I would do 5.

I started all this at the beginning of my summer vacation and after my vacation I could run 10 km without a lot of effort (when starting I could not really do even 3 km on one go). It just felt good to run. Then work started to get busy again with other people coming back from their vacations, winter came and all that which made it harder to train and to find time for it, that broke the training rhythm and I stopped.

But I was surprised at how well HIIT worked.

After some time of doing HIIT and improving, I stopped with adding repetitions and just ran in a sane pace, since it felt nice.


So they actually eat ~ 2000 calories in one sitting with this diet?


Whenever I read about stress' effects on the body, I always wonder about exercise. Exercise is an example of stress, or at the very least causes similar symptoms (rapid heartbeat, breathing difficulties, cortisol and adrenaline spikes). Why is it that exercise is so good and stress is so bad?


Chronic stress is problematic. The body regularly experience spikes in stress.

Stress tends to increase cortisol, which results in precursor (progesterone/pregnenolone) depletion. Progesterone/pregnenolone also become DHEA, testosterone, etc. If the body doesn't have enough raw material to produce needed hormones, many issues can accumulate.

Cortisol tends to slow thyroid function, lead to increased estrogens, and put the body in a state of degeneration. Brief states of degeneration and halting of healing/renewal processes are fine, as it's necessary to produce flight/flight energy. On the other hand, the body isn't able to heal/build if sustained.


I wonder if there have been any studies on the effects of intermittent stress on the human body. Might there be healthy outcomes from regularly putting the body under short term stress that is then successfully resolved, almost like psychological exercise?


The body is regularly stressed. It means little when normal. It's problematic when chronic, as it interferes with healing and causes degeneration. I suppose exercise is an example of a stressor that has positive effects.


Just interview a bunch of STEM majors throughout the semester and you’ll probably get the answers you’re looking for.


Too much exercise is also injurious. That said, I have subjectively experienced an adrenaline rush for stupid reasons and chosen to do nothing with it — no run, no fight — and the subsequent downer felt terrible; as a result of this, I assume that physical exertion produces extra substances in the body which mitigate the stresses in much the same way that purely psychological stress is countered with external substances such as alcohol, weed, etc., or clinical antidepressants.


Really interesting point. Body gets all charged up and then needs to work to eliminate byproducts through slow manual processes instead of them being excreted through exercise. That would make a lot of sense.


Could it be that exercise also rises BP and HR which causes all negative substances to reach kidneys/liver quicker?


I'm guessing it's like the way driving your car fast isn't bad for it, but sitting in your driveway revving the engine is bad for it.


What a fascinating read! More to learn about how the body handles stress, no doubt, but an interesting idea.


From the article: “If further evidence of the importance of healthy mitochondria continues to emerge, drugs that focus on regulating cellular energy production instead could become a new line of defense for psychiatric and biological disorders.”

I know enough exercise helps regulate my mood. Seems like there’s a link there somewhere.


Total bodily stress causes such a large cascade of changes that you almost learn nothing by finding a connection.


Sorry? Could you clarify?


"Oh here's a new biochemical path connected to exercise."

"Oh sweet I guess I should exercise then."

Except the basis for the decision to exercise or not has already been confirmed in inumerous ways on these grounds, and it is redundant since we should expect massive stress of any sort (exercise included) to result in large cascading changes in the body.

Or the other way around, the body is so intricate that any individual biochemical pathway is unlikely to play a significant role in the whole, and so we should explain things in terms of the whole to actually learn something. The OP mentioned mood. But there are a lot of unnoticed alternative pathways at play here, why wouldn't they also have a connection to mood?

Maybe if you were in particular seeking a way to mimic exercise with drugs this kind of thing becomes more useful.


Though, conversely, if we can strongly associate a given stimulus or process with a respose, regardless of understanding the specific pathway(s), is that not useful information?

It was the basis of much practical knowledge for most of history.


Not OP, but my interpretation: exercise isn't confined to mentally or socially induced stress, and perhaps the body tolerates it better.


This quote from the article makes no sense: “Mitochondrial DNA is probably the most sensitive thing in your body,” says Douglas Wallace.

He's not talking about the DNA being affected (as if it were sensitive to something), he's talking about it _causing_ effects.

If I'm missing something, please correct me. Otherwise I'll assume he misspoke.


> he's talking about it _causing_ effects.

Yes, that's what the article is about? It's explained in the second half, no? Starting at "But how was this inflammation triggered by mitochondrial DNA leaking out of cells?"


By that interpretation, he misspoke when he said the DNA is sensitive. What he should have said is that the _body_ is sensitive _to_ the DNA. That was my point.

And I only point it out because, given he's an expert on the topic, it's always possible that he actually meant to say it this way and that I, being a layperson, missed something that would explain it.


Is this why some folks with stress and anxiety report feeling better when taking coenzyme q10 (coq10) supplements? It allegedly improves mitochondrial function...


I wonder if this may be an explanation for the mood-leveling effects of ketogenic dieting.


I wasn’t aware of this benefit... have you or people you know seen these effects from keto? Might be worth a try, if that’s the case...


Been keto for 3+ years. Consistently, when breaking ketosis (eating carbs) I...

1. Feel foggy, slow, like I had some alcohol, without any of the pleasant euphoria.

2. Am more likely to get into arguments.

3. Become anxious.

And it gets much worse with high-glycemic foods(sugar).

No more cheat days with ben and jerry for me :(


Definitely more stability in my mood with keto. Higher cognitive function, and perhaps the best part - easier anger management as a side effect. Helped me get off my antidepressants too.


Would be interesting to see if there is any relationship between physical exercise, fasting, meditation or diet in general.




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