When I get the new meter and strips (those buggers are expensive, sheesh), the first experiment I'll do will be trying to keep my fat at 80% or above, and my protein obviously lower. No carbs; I've done that experiment already. Several times.

A year or so ago I cut out *red* meat for a while, eating only chicken, pork, and fish, and I quite quickly lost a whole bunch more weight, dipping down into the very low 140s. However, 1) I felt like absolute crap (and one of the great things for me about eating the way I do is I *never* feel fatigued or crappy), and 2) it turned out I was eating around 900 calories a day! I had no idea until I plugged it into NutritionData.com. So I don't know what variable -- calories, fat, protein, meat type, space radiation -- caused the weight loss and the fatigue.

Just for reference, prior to VLC/ZC, I couldn't lose weight on 1200 cals/day, but had to drop to an average of 500 or so to see verrrrry slooooow weight loss. Crazy, but true, and unsustainable too. I could only go a couple months at a time before caving, and everything I'd lost would come rushing back (with friends), of course.

The too much protein argument says something about what's going on inside. From Wikipedia:
http://en.wikipedia.org/wiki/Glucagon

As we can see, protein (specific amino acids) stimulates glucagon, which in turn causes blood glucose to rise. But when there is no dietary carbohydrates, this glucose is derived from internal stores - glycogen and glycerol. If that's how it works, then we can't blame too much protein for lack of progress because it's basically neutral since it causes both insulin and glucagon to rise, with opposing actions. Yet even with the tendency to produce glycerol to compensate for its use to produce glucose, there is no other source of substrates besides those therefore the overall tendency is to deplete those sources of substrates. And there's just not enough dietary protein to make up the difference if it used as a substrate.

This tells me there is obviously something else going on here when progress stops, slows or even reverses in my case. It's likely not glucagon because of its tendency to deplete internal stores. It's most likely insulin, but probably not due to dietary protein either. So look for anything that can keep insulin too high, in spite of your best efforts. Testing BG is not so useful because of glucagon which keeps it from dropping. Testing ketones is much more useful because it's a proxy for insulin. Testing insulin directly is obviously the best option.

Bear in mind, we're discussing this in a thread about insulin signaling in very sick cancer patients, where even some of those see an effect from dietary carbohydrates restriction. So it's not like it would work less well in relatively healthier people. Yet, that pilot study says there's obviously something else going on for those patients that didn't see an effect from the same dietary carbohydrates restriction, and this happens to be related to insulin signaling and ketosis.

I just got an idea to check for efficacy of cutting carbs besides blood glucose, ketones and insulin. Check blood pressure and heart rate. This idea is only a working hypothesis because I didn't look for any data to support it yet so bear with me and if you have any idea about it let us know.

Here's how it should work. Work by Jeff Volek et al shows that we can have a significant effect on heath without any weight loss, and long before any weight is lost as the case may be. The point is that things like BP and HR are also indicators of overall health, and those should improve too once we cut carbs, and should improve very quickly and this gives us an almost immediate indicator of efficacy of cutting carbs.

Here's what to do. Check BP and HR and put the results on a chart against carb intake. If you're one of those with the white coat syndrome, practice with the BP meter until you are comfortable with it and this should reduce the variability of the results you get. Check BP 3 times and record the average. There's a few ways to check BP with either a home machine or at the drugstore for free. You can do HR just with a watch but those machines usually measure both BP and HR.

Now, here's the tricky part. You have to either eat less or more carbs because we're checking the effect of carb intake on BP and HR. If you just eat the same, we won't see any change. We want to see useful information. So, if you usually eat 50g carbs/day, eat none today and do the tests. If you usually eat none, eat 50g today and do the tests. Of course, you have to get baseline measurements to compare to so before you change carb intake, take a few measurements and put those on a chart. I'd say a week's worth of baseline numbers should be enough for our purpose here. Then a week's worth of test numbers should do it. Then another week's worth of return-to-baseline numbers should conclude the experiment.

Next, once that's done, we determine if it's all about carbs, or if there's something else going on here. If you see an effect, then it's probably only or mostly about carbs. If you don't see an effect, then there's probably something else going on. If we see an effect but it's weak, depending on the strength of the effect, we can determine the strength of this something else.

I think it needs a bit of polishing but you get the idea.

On the cancer thing--they take a bunch of mice, put them on ketogenic diets, all the same ratios, either ad lib fed or calorie restricted. These mice vary more than us human--but I wonder what would happen if they treated them like patients? Or at least treated them the way patients should be treated--as individuals. Adjusting the diet for each individual to whatever degree necessary to get a certain level of ketosis.

Steve Phinney describes nutritional ketosis as a fairly fragile state--and it makes sense that the harder it is for a person to get there, the more fragile the state. Jimmy Moore's being pretty quiet about his menu, but he keeps giving his protein intake--it's a pretty tight range, I think it's 75 to 80 grams a day. If you take his word that he really needs to hold it that tight--you can see where, just winging it, a person with similar difficulty getting there would be a lot better off if they had a ketone meter. Too little protein, and you're likely to get paranoid about lean mass loss (I know I'm prone to that). That's probably something that could help with as well; above a certain level of ketosis, I think probably you're not getting enough protein to avoid some lean mass loss. If protein was just a little too low, I could see a person having trouble maintaining the diet--the body basically rejecting the diet.

I must have too much time on my hands. I'm getting blabbier on line.

Teaser, I think that's the whole point of a pilot study - to make people talk about the possibilities.

Hmmn, what if the BP and HR are normal, would you still expect to see variation?

I would do this experiment but I haven't a meter (HR is easy, BP not so much, and the size of my arm compared to drugstore meters is truly hilarious... I'm out of money or I'd see if there was a finger-one I could buy on amazon).

I sometimes think it's one of the more surreal things that aside from my 'mountain range triangle BG readings' (even on zero food for a day), so far there don't seem to be any other basic measures that show anything out of whack. Which seems so unlikely -- I mean really, seriously, if you weigh over 400#, doesn't it seem like every system in the body ought to be wailing OMG or something?! Maybe it's the 'adipose' system wailing and we just don't know how to measure it except with calipers...

My resting heart rate is fairly high (low 80s) compared to what it was when I was a young adult and athletic but that's probably as much from being super sedentary as being fat. My blood pressure is normal as of... a few months ago (always has been, except when pregnant it was very high, and normal 10 minutes after delivering). Varies very slightly -- 116-122 over 80-84, fuzzy memory from the ~annual visits to the clinic doc the last 5-6 years. I think last time it was to get a tetanus shot for the kid and an update for me.

I always feel like the doctor is looking at me like, "You weigh over 400 pounds and you're only here because you got an infected wasp bite?!" (Or once, because I was eating gluten and my asthma got out of control so I got an inhaler.) Had I been truly ill I wouldn't have visited the doctor, given how I feel about it all LOL. I only go for stupid stuff I feel like they might be competent to handle.

Is ketosis fragile? I mean, I can see that perhaps overeating carbs or protein could reduce or stop it, but wouldn't undereating keep it present, even if chewing up LBM?

T: You should be chatty. You have a lot of lost time to make up for. ;-)

PJ

Here, we're not trying to find out if it's normal, but if there's a variation and how wide this variation is.

My BP went from 90/60 to 120/80. It's still normal but it's not normal that it went up suddenly. It had originally went down from 130/80 however I have no data that can tell me exactly how it happened since those numbers are from a period when I didn't know the first thing about anything. My HR was around 55, then went up to around 80 and stuck there. Even here, it's still normal but it's not normal that it went up suddenly and stayed there.

The standard numbers have a very wide range. BP goes up and down quickly for various reasons. External stress, activity, diet, illness, etc. Measuring once gives nothing meaningful but here my idea is to measure several times daily over a few weeks and put the numbers on a chart correlated with changes in carb intake.

The goal is to eliminate dietary factors - carbs - so we can then focus on what else is really happening - if carbs is not the only thing happening of course. The goal is also to determine just how strong dietary factors are. If it's all about carbs, then we should see a very significant change in BP, HR, and if we test ketones and insulin, those as well. If there's something else going on, then the changes will be less significant or none at all.

My idea stems from the fact that carbs have an effect on insulin, which in turn has an effect on the hormones that regulate BP and most likely HR as well. It could also be that carbs have an independent effect on those other hormones. I'm thinking of epinephrine mainly.

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

If you can't measure BP, do HR anyway and see how that goes. Epinephrine also regulates HR. Make sure you're calm so sit and wait for 5-10 minutes before measuring and repeat a couple more times right away to get an average. Do all measurements the same way to reduce variability. If all you got is a watch, you can take a 15 seconds measurement and do the math.

Of course, all this is just if you can't measure ketones or insulin, or if you want to get more information for a more complete understanding of what's going on. Also, measuring BP and HR is most likely a proxy for epinephrine.

If we think high BP is due to sedentary, we could think exercise will fix it. But if we consider that sedentary could be due to low energy, then we could also consider that high BP could be due to that too independently. And if it's low energy, then exercise is out of the question. That's one of my problems.

certainly my BP went down eating low carb, despite being very sedentary - to the point that even during a high stress surgical procedure it was normal (to the disgust of the nurse ) - but I'm not sure if was just low carb though, as I added magnesium and d3.

But my pulse does increase with carbs. My resting pulse rate is around 70, add a high carb day and it is around 90.

Lee

I'll be curious to see how it works out, Rose. The high fat/mod protein WOE makes sense, but most people seem to get hungry on it.

On M Levac's comment "targeting insulin inhibition is like targeting cholesterol. Remember statins? It completely ignores the cause and allows it to continue." I don't think that that was really our approach. In fact, one of the things that encouraged us is how the big result that came out of the studies on caloric restriction was the extent to which the cell biology pointed to insulin. I described this in my post on the Washington DC meeting http://wp.me/p16vK0-dT and http://wp.me/p16vK0-e4. In any case, we think that there are certainly more question than answers -- in fact, my main point was that we can ask good questions now, like how does the demonstrable benefit of carb restriction fit into the bigger picture of cell signaling. Also, I think the scientific world is just beginning to see the potential of ketone bodies. We don't really even know about the individual personal differences of the type described here. While I don't think we know enough to interpret things, it is certainly worth considering that lower than expected ketone bodies may reflect that they are being used and therefore not accumulating.

Richard David Feinman

I agree, Richard. We must consider all possibilities until we find out what's really going on. However, with ketones possibly being used instead of accumulating in the blood, thus the low blood ketone level, we have evidence elsewhere that this is not very likely. It's the rise in blood glucose in response to exercise. This rise is most likely driven by demand. Ketones, being a fuel as well, should behave the same way with increased expenditure.

So, if ketones are used up fast enough, then instead of low ketone level, we should see an increase in ketone level in response to increased usage, just as we see with glucose, and most likely fatty acids as well. Once Eout returns to baseline, ketone, glucose and fatty acid level should go back down accordingly. If we don't see a rise in ketone level, either with low-carb or with exercise, we should consider that something is interfering with the regulation of ketone production, most likely insulin and the liver. This should be our nul hypothesis both for blood ketone level, and for potential interference with its regulation.

Always exciting to see Dr. Feinman posting here!

High blood pressure is not from being sedentary, at least not alone. I am insanely sedentary and I weigh over 400 pounds and I don't have high blood pressure. Much to the amazement of every nurse who occasionally tests it.

PJ

Part 2: Targeting insulin inhibition as a metabolic therapy in advanced cancer. Part 2. The hypothesis.

Very interesting. Makes a lot of sense to me.