Mitochondria get nasty when they get hurt

This is the full text of a very dense little article with a lot of gold embedded in it:

Mitochondrial reactive oxygen species drive proinflammatory cytokine production

Mitochondria are an appropriate fascination for any science writer who covers neurology, immunology, inflammation, or intracellular mechanisms — so here’s the BioWizardry primer on mitochondria.

Good primer from this article, in sci-speak:

“Mitochondria generate ATP through aerobic respiration, whereby glucose, pyruvate, and NADH are oxidized, thus generating ROS [Reactive Oxygen Species, or free radicals] as a byproduct. In normal circumstances, the deleterious effects caused by the highly reactive nature of ROS are balanced by the presence of antioxidants, including glutathione, carotenoids, and antioxidant enzymes such as catalase and glutathione peroxidase.”

Here’s a bit more insight into these fabulous little factories, gleaned from this article (which otherwise focuses on the mechanisms of a rare condition called TRAPS.)

The reason for the antioxidants we take so much of to support our overloaded nervous systems is, they act specifically against reactive oxygen species, ROS. ROS are chemically reactive molecules which contain oxygen, and use the oxygen to wreak a certain amount of biological havoc. As the BioWizardry mitochondria primer mentions, mitochondria are the biggest consumers and the biggest producers of antioxidants, and the nerve and muscle cells have the biggest population of mitochondria. Therefore, when your nervous system is under siege, as in chronic pain or anxiety or lupus or MCS or what-have-you, your body may need far more antioxidants than you can get in your food to support all those mitochondria, so they can keep making energy for your cells to use in their work.

“High levels of reactive oxygen species (ROS) are observed in chronic human diseases such as neurodegeneration, Crohn’s disease, and cancer. In addition to the presence of oxidative stress, these diseases are also characterized by deregulated inflammatory responses, including but not limited to proinflammatory cytokine production. New work exploring the mechanisms linking ROS and inflammation find that ROS derived from mitochondria act as signaltransducing molecules that provoke the up-regulation of inflammatory cytokine subsets via distinct molecular pathways.”

OK, so, the mitochondria (the biggest producers and the biggest users of antioxidants) generate a specific set of ROS which trigger inflammatory cytokines.

That means, pissed-off mitochondrial cells trigger pain.

Mitochondria get pissed off by being damaged and not being able to clean themselves up:

“Mitophagy is a specialized form of autophagy that refers to the specific catabolism of mitochondria. Pharmacological inhibition of autophagy by treatment of macrophages with 3-methyladenine resulted in the accumulation of damaged mitochondria and an increase in the net amount of mtROS…”

(Autophagy is the word for when the damaged/unhealthy cell consumes itself so the damage is cleaned up and their contents get recycled for healthy cells. Cells are all about the greater good. When they’re too damaged to do their jobs, they recycle themselves.)

AND this happens whether autophagy is prevented upstream or midstream:

“Thus, autophagy regulates baseline mtROS production from individual mitochondria by a yet to be identified mechanism.”

Mind you, only so many mitochondria can autophage at a time. When damage exceeds the cell’s ability to keep up with the housework, you have a lot of damaged mitochondria.
dyed  microscopic image of busted mitochondria showing the inner reticulated membrane
So, take care of those mitochondria.

More on antioxidants will be coming soon. Naturally, it’s not as simple as it looks.

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Clarifying nutrition: focus on Source, Process, and Time

This table shows the antioxidant contents of 3,000 foods:

The Antioxidant Food Table

On first glance, I was annoyed, because there was so much redundancy in the foods examined: 11 entries for blackberries? Couldn’t they make up their minds?

On closer inspection, a deeper story emerged. Take a look at this and see what you find:

Product Label Procured in Antiox. (mmol/100g) Prep
Blackberries, cultivated USA 4.02 6
Blackberries, cultivated Solabaer, Sola, Norway Norway 4.13 3
Blackberries, cultivated Norway 6.14 3
Blackberries, cultivated Belgium Norway 3.84 3
Blackberries, cultivated, canned, drained S&W Fine Food, USA Norway 2.34 3
Blackberries, cultivated, frozen Local grocery USA 4.06 6
Blackberries, cultivated, frozen Wholesaler USA 3.89 6
Blackberries, cultivated, with sugar Findus, Norway Norway 4.76 3
Blackberries, Dessert Berries, without sugar, frozen Norske Dessertbaer, Norway (berries from Poland) Norway 5.98 3
Blackberries, dried, “Loch Ness” The Norwegian Crop Institute Norway 37.08 5
Blackberries, wild Norway Norway 6.13 4

Comments:

3 Purchased in grocery store, restaurant, cafe, bakery or marketplace.
4 Handpicked or received directly from supplier.
5 Previously published in Halvorsen et al. 2002 or Dragland et al. 2003
6 Previously published in Halvorsen et al. 2006.

Notice how much variation there is?

This table indicates what’s behind those eternally confusing reports about which food has the  most antioxidant activity.

With a spread of more than tenfold in the antioxidant activity in blackberries, you simply have to look at two more factors:

  • Source
  • Preparation
Understanding these two critical factors helps clarify a lot of red-herring driven confusion over which foods are most nutritious.

It’s a reminder of something we know, but tend to forget in the barrage of information and anxiety around food. 

  • Plants and animals need nutrients, water, sunshine and air to grow; the quality and quantity of these things affects what they produce.
    More species-appropriate and healthful growing environments produce more nutritious food than inappropriate or unhealthful environments.
    Different strains of the same species have different attributes, as someone who has tasted longhorn steak and kobe steak side-by-side could probably tell you.
  • Food nutrients are reactive, which means that heat and light are going to make them change over time.
    If they weren’t reactive, they wouldn’t be nutrients, because nutrients need to be amenable to digestion and assimilation — that is, physical and chemical reactions — before they can do us any good.
    Therefore, food nutrients are susceptible to heat, light and time.

Source matters

Cultivated blackberries from 3 different places had an antioxidant score that varied by roughly a third. That’s a significant variation!

There was only one sample of wild berries, which rated about the same as the best of the cultivated fresh berries from the same region. Wild strains of berries are generally more nutritious, so it should be said that this study does not specify if these berries were from a wild strain, or from a cultivated strain found growing in the wild. Not everyone realizes there’s a difference, but heredity matters (kobe/longhorn.)

Preparation matters

Processing makes a huge difference in the amount of nutrition available per, say, 100 grams.

Notice how the canned berries, which are subjected to considerable heat in the canning process, have the least antioxidants.

The frozen berries, which are meant to last awhile (thus being subject to time) have less bounce per ounce than some, but more than the canned berries.

The fresh Norwegian berries that travelled to Belgium are likewise impoverished, and the distinguishing factor between them and the Norwegian berries in Norway is the transit… time.

This may also be due to using a strain of blackberry that withstands transport better — a trait which, in produce, often goes with a lower nutritional profile.

If fruit is dried correctly (a big “if”), then it retains much of its nutritional value and has the considerable advantage of concentrating it into a smaller quantity. Thus, the 100gm of dried, possibly higher-quality berries turned out to have the biggest antioxidant kick — by a factor of roughly 10 over frozen berries.

Subjective matters

I’ve been thinking about this article since I read it a month ago.

Then, as I was struggling with brain fog this weekend, I got a pair of half-pints of organic raspberries from a large commercial producer which is famous for consistently mild, sweet-smelling berries that hold their shape despite being shipped all over. They were on sale.

I ate a whole package, hoping for that antioxidant kick that would chase some of the fog away. Not wanting too much sugar in my system (and hating to spend that much money in one sitting), I hesitated before starting on the second package, but no good. I might as well have been eating cardboard for all the good it did. I began to wonder if I should bother with raspberries at all, given how every bite I eat has to matter.

The next day, I stopped at a roadside stand and picked up a single half-pint of organic raspberries from a farmstand, for slightly more than the brand-name berries cost on sale, but less than they cost otherwise. (Farmstands are generally worth the gas I spend on finding and mapping them.) They were much smaller, much darker, and some of them were squashed. They wound up spilling in the car, and I pulled over to scoop them up and keep them from messing up the rest of my shopping. I quickly gave up on extracting them neatly, and just shoved the spilled half into my mouth.

Quite apart from the flavor explosion — which was an eye-opener in itself — within a minute, the fog had lifted. My eyes were sharper and my head was clearer than it had been in awhile. THAT was the antioxidant kick. It lasted for hours, and I got another one when I ate the second half.

Summary and context

A lot of the fuss over what to eat can be resolved with a little common sense and remembering what you learned in grade school when you were sprouting beans in little cups.

How fresh your food is, probably matters more than exactly what it is.

How well it was grown, probably matters more than the packaging.

And, if you’re lucky enough to live near farm country, roadside stands are worth your time.

If not, build farmer’s markets into your schedule, because they bring the fresh food right to your neighborhood, with very little time between the soil and you.

I’ve found that each bite of more nutritious food is more rewarding in every sense, and I wind up needing less to meet my needs. It’s economical in the long run, although I remember it took a few months of eating good food voraciously to catch my impoverished system up. That cost a lot up front, but it paid off in the end: my system became more efficient and my tastes evolved for satiation, not overstimulation. I eat enough and am genuinely pleased; that eternal nervous quest for more-more-more is gone.

Grocery stores are for filling in after the farmer’s market and roadside stands, in my view. I have a limited budget and stringent nutritional needs, so I’ve come to that realization the hard way. This study just reinforces my discovery in a different way.

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CRPS, ANS dysfunction, and chronic vertigo

The central nervous system is bathed in fluid. This fluid provides a buffer against shock, as well as providing a good medium for the transmission of chemical signals. (Electrical signals are handled by the neurons.) The central nervous system is extremely sensitive to dehydration, which is why headaches are so common: most people are somewhat dehydrated. We consider ourselves too busy to drink water and whizz it out again.

Water is also the main ingredient of blood and lymph. These two essential fluids bring nutrition to the cells, transport chemical signals such as hormones and regulatory signals, and carry away cellular garbage. When there’s not enough of them, that doesn’t happen very well. More garbage piles up in the tissues, aging happens faster, disease trends faster, our muscles get stiffer, it’s harder to recuperate from injuries and illnesses, our sex lives suffer, and we just don’t feel as good.

With that in mind, not having the time to drink in water, process it through, and whizz it out again doesn’t really make sense, but a lot of us are really attached to that idea.

Reality checks

One of the really ducky things about diseases like CRPS, especially when there is strong autonomic involvement, is that normal quantities of fluids (and vitamins, proteins, and other nutrients) are often inadequate to our unusual metabolic needs. It may be possible for a basically healthy person to meet all their needs with three good meals and three or four liters of water per day, but for systems so consistently under siege as those with CRPS, it may be impossible to meet metabolic needs within these (otherwise very reasonable) parameters.

I have several friends with terrible vertigo, due to autonomic dysfunction in CRPS. This isn’t the, “I held my breath too long,” kind of dizziness. This is the kind of dizziness where you can’t keep your feet under you, you feel like you’re going to throw up, and it JUST WON’T QUIT.

The mechanism behind this has only been researched recently. It’s not very well understood. I’m hoping for an informative comment from an expert on this…

What’s happening (partly) is that the vessels, which are directed by the autonomic nervous system, are flopping open too much. This means that the normal amount of fluid in the blood, lymph, and cerebrospinal fluid has to fill a space that’s considerably larger than normal. What you get is a type of hypovolemic shock, where the brain and major organs simply can’t get enough nutrition, oxygen, and garbage collection.

This normally happens on a short-term basis, after some assault on the system; normally, it’s either corrected quickly, or the person dies.

There are very few instances where this happens continuously over time, but with CRPS, some people have to live with it. It can make doing anything impossible, and if you try to imagine, just for 5 minutes, what it’s like to be that desperately dizzy and try to do anything — even get a fork to your mouth without bloodshed — you’ll see what I mean.

Sometimes, these symptoms can be somewhat reduced. There are pharmaceutical and mechanical approaches, each with its drawbacks and benefits. Since doctors (and many patients) tend to think in terms of pharmaceuticals first, let’s start there.

Pharmaceutical management

Whenever you think in terms of disease and pharmaceuticals, it’s important to keep in mind that:

  • Every system is unique.
  • Every system with CRPS is even stranger.
  • Unless you’re a doctor getting a visit from a pharmaceutical rep, there is no such thing as a free lunch. Everything you take in affects your whole system. With our systems under siege, it behooves us to be mindful of our chemistry.

NB: This is not intended to diagnose, treat, or cure any disease. Consult your physician with any questions, and if your doctor can’t give you a credible answer, get a referral to someone who might be able to.

Vasopressors, which can help restrict blood vessel size, have mixed results. They depend on the regulatory system being able to work somewhat, which is problematic in CRPS. Moreover, they have their own side effects, and given what a cocktail of medications most people with CRPS are on anyway, this can be quite noticeable. It has to be handled on a case-by-case basis.

Anti-dizziness pills, such as Atarax, affect the central nervous system and tend to make people sleepy and goofy. They are related to antihistamines and acid-suppressing medications (H2 inhibitors), and for those with hotwired immune systems and the nutrient assimilation problems common in chronic CRPS, they’re not without side effects. Moreover, because they address only the generic mechanism for dizziness, but not the particular mechanism for CRPS/ANS vertigo, they don’t necessarily help in these cases. Also, case-by-case basis.

Some SSRIs, typically used as antidepressants but extremely effective for nerve pain, can also provide support for the ANS. There is additional benefit to the use of SSRIs, because of their assistance with the nerve pain component of CRPS; when they can also improve the autonomic nervous system, it’s a big deal. Naturally, SSRIs being the idiosyncratic category that they are, it can take a few tries to find the one that works best in each person’s system. As I learned the hard way, getting the dose right can be a long and interesting task, given the idiosyncratic nature of our systems.

Mechanical management

Mechanically, it’s possible to increase blood volume by taking in lots of fluids, even if you already drink “enough.” “Enough” is a relative term, and what’s “enough” for a person with a normal autonomic nervous system may be “completely inadequate” for somebody with vertigo due to CRPS.

Blood pressure is a complex system, involving more than just fluid, vessels and the brain. Maintaining electrolytes helps contribute to a healthier fluid balance, and towards that end, sometimes doctors suggest increasing your salt intake. That only raises your blood pressure when you already have a predisposition to high blood pressure, so it may not be obviously useful; however, adequate sodium is important in maintaining renal function and supporting potassium levels.

Potassium is another key electrolyte, along with magnesium (found in Epsom salt), calcium, and bicarbonate. It doesn’t take much; four or five of the smallest grains of Epsom salt, stirred into a glass of water, can make a noticeable difference when you are magnesium depleted. Also, it usually makes the water taste better.

It’s easy to tell when you’ve taken too much, partly because it doesn’t taste good, but especially when it gives you the runs. Less is generally better than more!

Bicarbonate is better managed by eating plenty of vegetables, rather than trying to supplement and get the dose just right. Having an overly alkaline system doesn’t feel very good, either.

Calcium and magnesium are present in food, especially if you’re eating plenty of nuts and leafy greens. If you have CRPS, you really want to eat plenty of nuts and leafy greens! They provide so much in the way of A and B vitamins, antioxidants, minerals (which support cellular processes and regulation), healthy fats (which help your body absorb your nutrients and protect your nerves), fiber, digestible protein (which helps your body absorb the calcium), and so much else of what your body really needs.

Activity, even horizontal activity, even just stretching out gently in bed, provides the body with much needed prompting about how to keep things moving. It keeps your muscles loose, so that your body is more comfortable to live in; it also activates sensors in your joints which communicate with your body’s regulatory mechanisms, and this helps with maintaining blood pressure (one can only hope it helps enough.)

Any movement is better than no movement.

Changes in position should happen slowly, which is terribly frustrating, but it’s going to take as long as it takes. If your body doesn’t get to move, it forgets how to handle itself in movement. This becomes a negative feedback loop.

So, keep moving, even if you’re not moving in any way that the doctor would recognize. Frankly, most doctors are somewhat limited in their ideas of what constitutes exercise. Most of them have no trouble walking from the car to the office, let alone from the bedroom to the kitchen.

Don’t let perfection assassinate your drive towards improvement. Do what you can, and don’t sweat the rest.

  • If you can’t run around the park, walk around the block;
  • If you can’t walk around the block, practice ballet or t’ai chi with one hand on the back of the sofa;
  • If you can’t do that, fire up YouTube and do chair qi gong or chair yoga;
  • If you can’t do that, stretch out gently in bed, and do range of motion exercises. (This is a wonderfully pretentious term for moving each limb all the way up, then all the way down; all the way in, then all the way out.)

There is always something you can do to keep your joints active.

Moving your joints sends a message to your regulatory centers that they need to pay a little more attention to your blood pressure. That’s why it’s important to stay active. Our regulatory systems are screwed up enough; we need to keep them gently tuned, and be persistent about it, even when it seems absurd to do so. The habit of activity will serve you well for the rest of your life.

I’m aware that there are some herbs that have tonic effects on blood pressure and possibly the ANS. I would love to learn more about that.

Assume there is a future, and that what you do, even little things, can change how it goes.

That’s a good general policy, anyway. Especially with CRPS.

While I’ve known all this for many years, applying it to CRPS has been an education. When I’m able to focus a little longer, I’ll put together some references. Meanwhile, any of you who have references, either to support or contradict any of this, would be very welcome to post them in the comments.

I look forward to better science and better medicine for chronic vertigo in CRPS. It’s so thoroughly disabling, yet so thoroughly underrated.

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Link between fast food and depression confirmed, not clarified

This article states that around 5% of non-depressed people go on to develop depression when they eat junk food of the baked-goods variety (like croissants, pecans spins and Twinkies) or fast food.

Link between fast food and depression confirmed

The authors assume the link is causal (fast/junk food causes depression), but I don’t see why. Many people only eat fast food and carb-rich junk food when they’re already depressed and want the temporary solace (and serotonin/insulin hit) of comfort food. It might be smarter to eat more trail mix, olives and avocados when we’re depressed, and leave out the Twinkies, but the fact is they cost more.

So, is the fast food/junk food self-medication for depression, contributor to depression, or both? It makes more sense to view it as a sign that something is amiss, rather than leaping to the conclusion that fast/junk food itself is the problem.

When people need to self-medicate, they’re going to find a way. And at least fast food is not going to cause as many accidents as alcohol, as much ruin as harder drugs, or as much disease as compulsive sex — all of which are popular forms of self-medication for depression.

Something to consider… We need not leap right to the blaming mentality. We can treat these changes in habits as useful clues instead.

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Blood sugar and mood

“ScienceDaily (2012-01-10) — Patients simultaneously treated for both Type 2 diabetes and depression improve medication compliance and significantly improve blood sugar and depression levels compared to patients receiving usual care, according to a new study.”

http://www.sciencedaily.com/releases/2012/01/120110093559.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fmind_brain+%28ScienceDaily%3A+Mind+%26+Brain+News%29

In plain English, this means that people with non-insulin-dependent diabetes need to be treated both for diabetes and depression; when that happens, twice as many get stable.

This falls under the Department of the Blitheringly Obvious, because — as anyone who has hypoglycemia, or has dealt with diabetics knows — depression is the first sign of low blood sugar; low or unstable blood sugar leads to poor decision-making, notably poor food choices; poor food choices lead to unstable blood sugar, and round and round we go.

To break the cycle, both must be addressed. Otherwise, the cycle continues feeding on itself… er, unfeeding on itself. Or something.

As anyone with common sense who has dealt with the mentally ill knows, the first intervention is a proper meal. It’s simply amazing how things improve with a little real food inside.

Unstable blood sugar worsens pain, impairs memory, and limits cognitive function. Low blood sugar specifically creates an unhappy state.

A hungry brain is not a happy brain!

Treating type II diabetes without treating depression, or treating depression without treating underlying type II diabetes, is not a recipe for success. The fact that as many as one third of these diabetic patients even get better, is pretty remarkable. Treat both, and over 60% of these people go back to cheerful, stable, productive lives — not needing sickleave, additional benefits, or other direct and indirect expenses.

Sounds like a good cost/benefit profile to me!

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Warning: Starvation and alcoholism don’t mix

The latest candidate for Dept. of the Blitheringly Obv.: Young people eating too little and drinking too much is worse than doing either alone. No, really??

Lasting damage to memory and thinking, more bad choices, and increased likelihood of developing chronic conditions later in life, are far more likely because the damage from each form of fashionable self-abuse compounds the other.

This idea is certainly high on the head-desk quotient, but the article is mostly clear and sensible:

http://www.sciencedaily.com/releases/2011/10/111017171506.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fmind_brain+%28ScienceDaily%3A+Mind+%26+Brain+News%29

They mention that the risks to women are higher ounce per ounce, but don’t say why; that vagueness is annoying and wrong, and science is far enough along to know better.

The idea that real food might be good for you is kind of a shocking idea, to some. Encourage them to get used to it. Fresh salad, berries, roast chicken, apples, baked potatoes, butternut squash … There are worse things. Like brain damage, cirrhosis, kidney failure, strokes, chronic fatigue, and HIV.

And looking really bad by 30.

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