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Comment by seaorg | Hacker News Reader

I don’t have the time or energy to write a full explanation, but my life has been consumed by this topic for the past two years. I became very ill after a stressful life event and it became clear to me that it involved mitochondria and inflammation, even though that was bizarre and inexplicable at first. I have been lost in the metabolic rabbit hole ever since. All I can say is that if you have a disease that is tangential to this issue, endogenous ketones will almost certainly have some kind of effect on your symptoms — for me they are almost a complete cure.

Take it from someone who’s whole life has revolved around this topic for years: this is a huge deal, it’s real. There is a medical revolution in the pipes having to do with metabolism and inflammation. This article isn’t a scam.

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There have been all kinds of studies pointing at mitochondrial dysfunction for things like migraine and epilepsy; and that a ketogenic diet can benefit those disorders. In fact, the ketogenic diet was developed specifically to treat epilepsy. It does seem to have some other downsides..

Had you told me a decade ago that stress could physically make you ill, I would have laughed at you. But having been down that road myself, I totally get it. In retrospect, it's weird how dismissive people are of this. Platitudes like "it's all in your head", while technically true, completely miss the point.

I hope something is in the pipes, but I'm skeptical of the timeline.

I have recently seen a sincerely incredible improvement in my migraines since I started taking supplements such as B vitamins, Magnesium and CoQ10 aimed specifically at facilitating mitochondrial function and other adjacent metabolic processes.

Severe migraine sufferer. At peak in bed 20 hours a day lights offs Almost a former one now. Those are all key vitamins that I take that have helped immensely. Would add vit D, e. Also anti inflammatory diet. Also eliminating caffeine.

Energy level isn’t where I want it, but getting better.

For me it's lack of sleep triggering migraines. If I go a few of days without enough sleep (going to bed late, being kept awake by kids, jetlag etc) then I often get a migraine.

Maybe there might some extra factor doing the real triggering such as the weather, etc, but I have noticed a clear correlation between lack of sleep and migraine.

Traveling to different continents for business trips often triggered a migraine at the end of the week.

If I'm working too much too late inot the nights for several days then I often get a migraine.

If I sleep poorly and wake up often due to my kids having a period of bad sleep, sickness etc, then I often have a migraine after a few days of this.

Drinking alcohol can also contribute as it makes the sleep less good and efficient.

Magnesium insufficiency is massively under diagnosed and under treated.

I suffer from chronic migraine, but vitamins made no difference. I take magnesium and vitamin D anyway, but have tried adding CoQ10 etc, to no avail.

Sumatriptan works if I'm awake when the migraine is starting. I recently started taking Erenumab, which also seems to be working to some extent (Severity of migraines is reduced).

I'm going to second this saying that I have similar sequela that were massively improved through the ketogenic diet. Also if anyone is going to try the ketogenic diet make sure to consume excess salt, potassium, and magnesium. Additionally it is very difficult to maintain your weight on the keto diet. I was only able to go for 6 months before I lost too much weight.

I can't even make it 5 days on keto before I switch back to carbs...

Does "endogenous ketones" just mean following a keto diet? What were your symptoms?

A quick google suggests 'endogenous ketones' are ketones produced from inside the body, as opposed to 'exogenous ketones' which are supplemented.

Fasting can make the body produce them too.

> There is a medical revolution in the pipes having to do with metabolism and inflammation.

Could you please elaborate and perhaps link relevant literature, I've been fascinated with inflammation

Yeah I see threads of this sort of argument coming from many different angles. I just ran across this paper[1] via a youtube review[2] which was mainly focused on diet/nutrition and metabolism, but again is looking at mitochondria and possible neurological connections. "The continuum of disrupted metabolic tempo, mitochondrial substrate congestion, and metabolic gridlock toward the development of non-communicable diseases":

The bioenergetic dysregulation could also prime for the emerging of [neurodegenerative disorders] (O’Neill and O’Driscoll 2015; Pugazhenthi, Qin, and Reddy 2017). Hyperglycemia, obesity and hyperglycemia could induce the extracellular amyloid b (Ab) plaques, hyperphosphorylated tau protein, neuronal loss, and cognitive dysfunction, while the Ab plaques might reciprocally induce [insulin resistance]. Together with the inflammation and oxidative stress, the hyperglycemic-generated advanced glycation end products (AGE) are also the critical cause of neurodegeneration (de Nazareth 2017; Pugazhenthi, Qin, and Reddy 2017). There is a decrease in the brian-derived neuro-trophic factors (BDNF) in both MetS and NDDs, such as Alzheimer’s disease (AD), Huntington’s disease, Parkinson’s disease, and depression (Motamedi, Karimi, and Jafari 2017). The concurrent mitochondrial dysfunction in obesity, T2D, and [insulin resistance] ultimately causes cognitive dysfunction (Pugazhenthi, Qin, and Reddy 2017). All these interrelated pathophysiologies suggest the common pathophysiologies of NCDs and NDDs. Prolonged bioenergetic dysregulation thus potentially contribute to cognitive dysfunction.

The tldr is you should go through periods of fed and fasted state metabolically (what they refer to as "pushing" and "pulling" energy into/from your body) - most Americans are constantly in the fed/pushing state which leads to metabolic dysregulation. Under this paradigm switching to a ketogenic diet would help restore metabolic function and lead to more time spent in the pulling state (due to lower insulin).

[1] https://www.researchgate.net/publication/352475880_The_conti... (full text)

[2] https://www.youtube.com/watch?v=WthvGKTKOH4

Anecdotally fasting is tough at the start, but the payoff is well worth it not just for the weight loss but in general overall feeling.

When not in a fasted state the ketogenic diet helps with the transition back and forth into a fasted state.

What else have you seen around this topic ? I was reading about NAD levels (i'm not even sure it's fully related, my mind is fuzzy these days).

Ketones are related to autophagy which de-junks our cells. The ketones trigger recycling because they're produced when the body runs out of stored sugar. Junk buildup is considered a hallmark of ageing in the SENS literature

I'm slightly annoyed about not reading anything beside SENS, do you know other groups like that ?

thanks

The book, "The Switch" (Clement) is a nice synthesis of recent research on metabolic health. It presents a case that managing metabolic state can mitigate most of the risk of cardio-vascular disease, cancer and mitochondrial damage. Concretely, the book suggests: 1) keep insulin and IGF low through diet, 2) eat a 4:1 or lower ratio of omega-6 to omega-3 fats (to keep cell walls permeable), 3) do a fasting mimicking diet (FMD) every couple of months to trigger autophagy for cellular cleanup.

You can google FMD - the idea is to induce autophagy. This can be measured during the diet with some efficacy by measuring your glucose-ketone index. In theory, the body has the tools to clean and repair cells, including mitochondrial damage, through autophagy.

In addition to FMD, there are a number of autophagy supplements being tested following the 2016 discovery of the role of the cellular mTor switch. To me, the safety and science behind Spermidine is quite compelling. NAD+ plus precursors are compelling. Rapamycin, Metformin and other solutions that target the mTor pathway are also gaining funding and beginning more experiments.

Ketosis is important to the formula. Juv Labs recently introduced a di-ester exogenous ketone that is intended to promote ketogenesis in the liver, and produce endogenous ketones as well. Eating lower glycemic index foods (ie, down-regulate insulin) for a couple days while taking these supplements is a nice way to experiment with how your body adjusts to a ketogenic state. On the other hand, mono-ester exogenous ketones are more for exercise performance.

Lastly, the Bulletproof podcast is a surprisingly consistent (and understandable) source of biohacking and longevity information and discussion. Check out the recent discussion about NAD+ as an example. Rhonda Patrick's Found My Fitness is also an amazing resource.

Very nice

Was it intermittent fasting or carbohydrate restriction that helped you in particular?

I second this. What i recommend: Paleo / Keto diet. Physical exercise. No sun screen in your face / around the eyes - get some direct sunlight for at least 10 minutes per day on your eyes. Throw away your sunglasses. Try it out. If you don't feel better after a while, go back to your old habits if you want.

> What i recommend: Paleo / Keto diet.

Based on what evidence?

> Physical exercise.

Exercise is usually great. Is there another type other than physical I don't know about?

> No sun screen in your face / around the eyes

And get wrinkles and skin cancer. Excellent!

> Throw away your sunglasses.

And get cataracts. Good one!

My apologies but these recommendations come across like the side of Dr. Bronner's soap bottle. Entertaining but I'm not sure how useful or scientific they are.

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