Mitochondria and Heart Disease

[francisstp]

As with any medical discovery, the focus is on developing new drugs to take advantage of the new knowledge. Aren't low-carb and IF influencing mitochodrial activity?



Malfunctioning Mitochondria May Cause Heart Disease (http://blog.wired.com/wiredscience/2008/02/could-malfuncti.html)


Scientists say they've found a new explanation -- and a perhaps a path to a new cure -- for heart disease.

In a study published today in Science, researchers led by UCLA molecular medicine professor Douglas Wallace modified a single mitochondrial gene in mice. Their hearts quickly wore out and broke down. Mitochondrial defects, which accumulate naturally during the course of a lifetime, have previously been found in diseased human heart tissue. However, it wasn't clear whether the defects were a cause or an effect of heart disease. The UCLA findings offer direct evidence of a causal connection.

By finding ways to rejuvenate or protect these cellular power generators, it may be possible to prevent heart disease, which kills over 600,000 Americans every year -- and that could be just the start. "This provides strong support for the concept that aging and age-related diseases are associated with a decline in mitochondrial functional associated with the age-related destruction of mitochondrial DNA," said Wallace in an email.

Mitochondria are structures called organelles, separate from the DNA-containing cell nucleus but vital to cellular functioning. They convert chemical energy provided by the food we eat into a form usable by our cells. The process goes on constantly in every cell in our bodies, but over time the parts run down. Stray oxygen molecules with an especially unstable configuration latch on to DNA in both the nucleus and, more dangerously, in mitochondria themselves.

Mitochondria have their own genes -- just seventeen altogether, but of paramount importance, and just a few mutations can cause malfunction, even shutdown.

To model the effects of this degeneration, the researchers added a mutation to mitochondria in a mouse egg. Once fertilized, the egg developed into a mouse riddled with defective mitochondria and, it turned out, defective hearts. Compared to normal mice, their cardiac tissue was thick and weak, robbed of its natural strength -- the same problems found in human heart disease. The mice developed their disease after just a year; normal mice don't have heart problems until they're at least two years old, said Wallace.

As with any rodent study, certain caveats are required, but other scientists have found high mitochondrial mutation rates in diseased human hearts. The Science study fits with those findings, suggesting that the connection is direct. Even more tantalizingly, Wallace and other mitochondrial medicine researchers believe that other age-related diseases, from diabetes and Alzheimer's to cancer, have the same mitochondrial roots.

They're now searching for ways of fixing that damage with mitochondria-targeting drugs. Among these are resveratrol, a compound that's gained notoriety among longevity hackers and was recently shown to prevent diabetes in mice. If the drugs work, they could change the way people live -- and die. And if they make it from the lab to people, things really get interesting: who owns them?

[joedoro]

As with any medical discovery, the focus is on developing new drugs to take advantage of the new knowledge. Aren't low-carb and IF influencing mitochodrial activity?

Sorry , what's IF ? Great reference.

I found the second part of GCBC, which talks about that the role of carbs in degenerative disease to have been fascinating. I think that part gets overshadowed by all the heart disease and obesity talk, which is too bad.

Drugs - per Willy Sutton - is where the money is! It's hard to make money off of free knowledge.

But the low carb industry sure does try. Such a simple idea - don't eat carbs. But somehow the same author can churn out a dozen independent books saying the same thing. Then throw in their websites with their exclusive expensive products of dubious worth and I'm not so sure big pharma is much worse. And long before we see a drug that will protect mitochondria, I am sure one of these websites will be touting their own special supplement purported to do the same thing. And it won't be cheap.

The most refreshing author in this whole area is Taubes who could have have made a great deal more money than he will with his present book, if he had allowed himself to have written a low carb diet book instead of the scholarly work that he did produce.

[bioteclady]

I don't know that we can conclude that mitochondrial mutations are at the root of mitochondrial malfunction. Certainly any genetic mutation that disrupts the biochemistry of energy production is going to result in a nonfunctional power plant. For a constantly contracting muscle like the heart this is obviously a very big problem.

However, the same oxidizer molecules that can lead to mutations, can be simultaneously attacking the cellular machinery already in place. Disrution of membranes and enzymes is likely to be happening well in advance of such mutations. You might have significant impairment of the power plant long before the blueprints get messed up and caused future versions to be nonoperational.

I personally think eating LC is the single best way to minimize the amount of oxidizers running around in your system. It is these oxidizers that cause inflammation which is at the root of so many of our chronic diseases. No amount of anti-oxidants will perform like simply eating the right diet because anti-oxidants might not be getting to the right compartments. This is especially true when it comes to mitochondria, since your anti-oxidant molecule would have to cross both the cell and mitochodrial membrane before it could do its protective work of scavenging oxidizers.

[bioteclady]

Sorry , what's IF ? Great reference.

But the low carb industry sure does try. Such a simple idea - don't eat carbs. But somehow the same author can churn out a dozen independent books saying the same thing. Then throw in their websites with their exclusive expensive products of dubious worth and I'm not so sure big pharma is much worse. And long before we see a drug that will protect mitochondria, I am sure one of these websites will be touting their own special supplement purported to do the same thing. And it won't be cheap.

There's one big difference between LC proponents trying to make a buck and big pharma. And that is that LC is the right way to approach the diseases of our affluent society. It is preventative medicine. Big pharma relies on a disease maintenance model, they keep you ailing and on the hook for their drugs for life. I have no problems with LC proponents trying to make a buck while they are spreading the word. Its like a preacher asking for donations so he can keep doing his good works. You don't begrudge someone for having an entrepreneurial spirit when what they are espousing isn't doing harm. LC writers are like the preachers, big pharma is like the crack dealer.

IF = intermittent fasting, a way of eating that says focuses on the timing of eating in addition to the type and quantity of the food itself. Its thought that it can give results similar to calorie restriction, namely, increased longevity and better health.

[tom sawyer]

Sorry, I didn't see my wife was logged in and I posted under her monicker. I'm sure she would agree with my summary, though she would probably have put it more succinctly and with fewer misspellings. Hehe

[joedoro]

There's one big difference between LC proponents trying to make a buck and big pharma. And that is that LC is the right way to approach the diseases of our affluent society. It is preventative medicine. Big pharma relies on a disease maintenance model, they keep you ailing and on the hook for their drugs for life. I have no problems with LC proponents trying to make a buck while they are spreading the word. Its like a preacher asking for donations so he can keep doing his good works. You don't begrudge someone for having an entrepreneurial spirit when what they are espousing isn't doing harm. LC writers are like the preachers, big pharma is like the crack dealer.

IF = intermittent fasting, a way of eating that says focuses on the timing of eating in addition to the type and quantity of the food itself. Its thought that it can give results similar to calorie restriction, namely, increased longevity and better health.

Thanks re: IF I've heard people talk about fasting but I'm not sure I understand it. For example, if I go 12 hours between meals because I'm not hungry, i.e. my cells are being supplied with enough energy so that hunger signals are not generated, is that considered a 12 hour fast? And if so, would that be the same as if I was deliberately not eating even though I might be ravinous with hunger thus implying at the cellular level I'm energy deficient?

I have no problem with people making a buck, but unfortunately, so many intertwine such a simple message with their special supplements and the need for a lifetime commitment to them. And the problem is, even though LC does work, and I agree the message needs to be spread, so much of their promotion comes across more as hucksterism than science. And as a physician, I can tell you that is the one thing that turns off docs. That's why there is so much direct to consumer advertising by big pharma, docs are seeing them as hucksters as well and it's getting harder and harder for them to get their drug reps into doctor's offices.

That's why I think Taubes' book is going to do more for LC than anything before. Today I've bought I think it's my 5th or 6th copy since I keep lending them to my colleagues and they never come back.

[Nancy LC]

I think the thing that sparked interest in IF in this forum was Dr. Eades posting on it here: http://www.proteinpower.com/drmike/2006/09/13/fast-way-to-better-health/

[pennink]

I love that my doctor is onboard with fasting.

She can't understand why Western people think you have to eat constantly. she explains that your body shouldn't be busy digesting all the time; that our ancient ancestors did not get food three times a day and we've bought into the stupid marketing ploys of the various food manufacturers.

She is totally convinced that along with low carb, the fasting is what is treating my heart disease. I've gone from 'three to five years to live' to 'negligible heart damage'.

So naysayers: stick that up your arses.

:lol:

[KarenJ]

I personally think eating LC is the single best way to minimize the amount of oxidizers running around in your system. It is these oxidizers that cause inflammation which is at the root of so many of our chronic diseases. No amount of anti-oxidants will perform like simply eating the right diet because anti-oxidants might not be getting to the right compartments. This is especially true when it comes to mitochondria, since your anti-oxidant molecule would have to cross both the cell and mitochodrial membrane before it could do its protective work of scavenging oxidizers.

That is what makes ALA such an important anti-oxidant, as it is both fat soluble and water soluble at the same time, making it available to the mitochondria.
The best dietary source is red meat. :thup:

To determine the fate of the more severe mtDNA mutations, we introduced mtDNAs containing two mutations that affect oxidative phosphorylation into the female mouse germ line.

I was wondering about the nature of the modification the researchers introduced. Did these modifications cause oxidative stress along the pathway? Or were the genes involved genes that turn on or off the ability to synthesize antioxidants or render them useless? I'm not sure if I'm absorbing this right.
Interesting stuff.

[ElleH]

Thanks re: IF I've heard people talk about fasting but I'm not sure I understand it. For example, if I go 12 hours between meals because I'm not hungry, i.e. my cells are being supplied with enough energy so that hunger signals are not generated, is that considered a 12 hour fast? And if so, would that be the same as if I was deliberately not eating even though I might be ravinous with hunger thus implying at the cellular level I'm energy deficient?

Yes, going 12 hours w/o eating is IF. Everyone does some form of IF, some just prolong the fasting period each day and eat then within a specified window of time. As to being "ravenous," hunger is a habit. Once you gradually begin to break your fast each day later, you'll find that your hunger adjusts to that. The key is gradually. Most people who just say, "Today I'm going to start IF and eat one meal a day between 5 and 7 pm," generally don't last very long, I've noticed. The people who gradually extend the overnight fast as their body allows are the ones who seem to do the best. I haven't researched it myself, but I understand there are tremendous health benefits to IF.

I personally do an 18/6 IF sort of naturally. I eat dinner about 6 pm, and I eat again around noon the next day. Fast for 18 hours, eat for 6. I can eat as much or as often as I need to during that 6 hours. I think about 18 hours is the "minimum" fasting period that is supposed to confer the benefits of IF. I personally like it b/c I can eat 2 bigger meals, as opposed to 3 smaller. I love big meals. Although lately I've been doing a smaller break~fast and larger dinner. I don't push my fasting window to be later than noonish right now. If you go over to the IF thread, you'll see that the "real" IFers are doing much longer fasts!

[kneebrace]

Thanks re: IF I've heard people talk about fasting but I'm not sure I understand it. For example, if I go 12 hours between meals because I'm not hungry, i.e. my cells are being supplied with enough energy so that hunger signals are not generated, is that considered a 12 hour fast? And if so, would that be the same as if I was deliberately not eating even though I might be ravinous with hunger thus implying at the cellular level I'm energy deficient?


Joe, if you gradually extend your 'normal' overnight fast you soon discover that you just don't feel hungry during it. So to use your example if you were aiming for a twelve hour waking fast (as Elle points out we all fast for at least 8 hrs overnight anyway) if you increased the fast length gradually enough (for your individual body) towards that 12hrs, you wouldn't ever feel hungry while you are fasting. Because when you do eat you eat to satisfaction. I personally can't resist feeling 'hungry', so it took me about three months of daily 'ramping up' to even get to fifteen hours. A year later and I can't see myself ever fasting for less than 18 hrs. The health/bodycomp improvements over just low carb are too remarkable.

So much about IF is counterintuitive. I get the impression from the way you use the word 'hunger' that you think feeling hungry means you need to eat. Apparently not. The human body can cope without dietary protein perfectly well (ie. no muscle loss) for up to forty eight hours after your last adequate protein intake, and even thin people have enough visceral fat to last them considerably longer (nobody here has attempted longer than 48hr fasts and I wouldn't recommend it).

Assuming that they were well nourished before they started fasting, micronutrient supply isn't depleted for at least that first 48 hrs. Metabolic rate increases for the first 24hrs of a fast, reverts to baseline for the next 24, and drops after that. Which may be why stalled low carbers are finding that IF is such an astonishingly effective way to get hunger free bodyfat loss moving again.

Anyway the key thing with IF is to make the transition to going longer between meals than your body has become accustomed to as gradual as you personally find comfortable. And 'hunger' is the signal that you are taking it too fast. I still feel 'mildly peckish ' just before I go to bed (about 11pm) after stopping eating at 8pm, but don't feel hungry at all the following day until about an hour before I break my fast at between 4 and 6pm.

Stuart

[Nancy LC]

It is possible that the IF benefits we see are simply due to calorie restriction.

[LessLiz]

I suspect that most are. I won't consider IF for one reason -- it would teach me to eat big meals again and that is the last thing I need. I've gotten so accustomed to portion control over the years that I tend to not eat a lot (volume) in a single meal. I figure if I eat a big meal once a day for a couple of weeks I'll be back to not being happy unless I consume a massive amount of food at a single sitting. And since I don't see myself ever doing IF for the rest of my life, that would be a very bad thing indeed.

[kneebrace]

It is possible that the IF benefits we see are simply due to calorie restriction.

Could well be. But the important distinction is that any other dietary approach that involves/leads to more calorie restriction than just simple low carb also produces either constant hunger or muscle loss. The beauty of adding IF to basic Low Carb is that you get increased bodyfat loss benefits without hunger and effortless muscle gain, all while eating considerably less food and whatever anti-inflammatory/oxidizing benefits that confers (like increased life expectancy etc.)

Liz, it's a bit of a misconception that IF necessarily means bigger meals. I've never liked either big meals or rushing my food. So I just eat a moderately sized meal somewhere during my 2- 4 hr eating window and graze for the rest. Because it's only a moderately sized meal, it doesn't completely satisfy my appetite so it's easy to really enjoy grazing for the rest of the eating window. I don't think I could do only a 1hr eating window because it would necessitate a large meal.

Stuart

[LC FP]

To determine the fate of the more severe mtDNA mutations, we introduced mtDNAs containing two mutations that affect oxidative phosphorylation into the female mouse germ line.


Originally Posted by KarenJ
I was wondering about the nature of the modification the researchers introduced. Did these modifications cause oxidative stress along the pathway? Or were the genes involved genes that turn on or off the ability to synthesize antioxidants or render them useless? I'm not sure if I'm absorbing this right.
Interesting stuff.
As I read this they're not manipulating natural antioxidants in mitochondria. They're altering the oxidative phosphorylation enzymes in the mitochondria. Theseare the enzymes that couple the energy released by the oxidation of food with the generation of the high-energy phosphate bonds on ATP. In other words, Theyre screwing up what mitochondria do.

So these modified mitochondria don't make useable energy well, and the bad mitochondria cause the cell to be starved for energy, and die. There is a big antioxidant system at work in mitochondria which neutralize the copious free radicals that efficient mitochondria produce, it is well described in Protein Power, I believe. Centered around arginine.

That is what makes ALA such an important anti-oxidant, as it is both fat soluble and water soluble at the same time, making it available to the mitochondria.
The best dietary source is red meat.
Do you mean alpha-linolenic acid? Good to hear its in red meat. Also flax seed oil. I never thought muchof flax seed oil but maybe I'll reconsider it. Already eat a ton of meat... :)

[KarenJ]

As I read this they're not manipulating natural antioxidants in mitochondria. They're altering the oxidative phosphorylation enzymes in the mitochondria. Theseare the enzymes that couple the energy released by the oxidation of food with the generation of the high-energy phosphate bonds on ATP. In other words, Theyre screwing up what mitochondria do.

So these modified mitochondria don't make useable energy well, and the bad mitochondria cause the cell to be starved for energy, and die. There is a big antioxidant system at work in mitochondria which neutralize the copious free radicals that efficient mitochondria produce, it is well described in Protein Power, I believe. Centered around arginine.


Do you mean alpha-linolenic acid? Good to hear its in red meat. Also flax seed oil. I never thought muchof flax seed oil but maybe I'll reconsider it. Already eat a ton of meat... :)


Ahh! Finally a relevant post on the actual topic. :wave: I was referring to Alpha Lipoic Acid, not Alpha Linolenic acid. But the difference bears merit, and I have no clue what the difference is.

From what I understand, Alpha Lipoic Acid is an antioxidant derived from meat and veggie based sources, Alpha Linolinic acid is derived from mostly veggie sources? I'm not really clear on that, but thank you for your intelligent post.

I've gotten to the point of printing out a huge poster of the mitochondrian oxidative phosphorylation pathway, and even trying to interpret the chemistry. No go here. BioChem is not for me.

[kneebrace]

From what I understand, Alpha Lipoic Acid is an antioxidant derived from meat and veggie based sources, Alpha Linolinic acid is derived from mostly veggie sources? I'm not really clear on that, but thank you for your intelligent post.



Karen, AFAIK alpha linolenic acid is an omega 3 fatty acid that is found in green leafy vegetables and some seed oils. The human body converts it with some difficulty to EPA and DHA, also found already converted in cold water fish oils.

Stuart

[LC FP]

Alpha linolenic is the 18 carbon omega-3 fatty acid that your body can convert (theoretically) into fish oil-- EPA(20 carbon) and DHA (22 carbon). It is one of the two "essential" fatty acids. The other being Linoleic acid, which converts to arichidonic acid. Most people are pretty inefficient at converting ALA to EPA, so they should just use fish oil itself (unless they're vegans), since EPA and DHA are what your body really requires. Barry Sears wrote a very understandable description of this system and its implications for inflammation in his Omega-Zone book.

I don't know much about alpha lipoic acid. Just that it's recommended as a supplement by some. And as a hell of an antioxidant by others... :)

[joedoro]

the difficulty I see with research like this is that until human studies are done we won't know if it has anything to do with human disease. It might be interesting but to think you can apply it to people strkes me as odd. Just look at the results of vitamin supplementation in patients at high risk of lung cancer. Animal studies suggested it would be good.

I remember an old neursurgeon who would come to tumor board and listen to everyone hypothesize and argue as to what an abnormality on CT scan or MRI was going to be and he would sit in the back and finally someone would ask his opinion and he would always say - "Well, when I take it out we'll know what it is"