62 replies to this topic

[TheFountain]

When you're in fat burning mode, as many here may be, it takes longer to metabolize a high glucose load.

If that is the case than most of the diets we discuss here should be questioned. But if it was we would have a lot more to go on in my opinion. Thus far I see no reason to suppose that primal, CR and some well constructed vegan/vegetarian diets are not still the best.

Edited by TheFountain, 14 July 2012 - 07:37 PM.

[Noodly]

I can't explain why, but under the zone diet paradigm advanced by Barry Sears low protein intake would increase levels of chronic inflammation in the body. This could actually accelerate the development of chronic disease and work against the benefits of CR.

I practice anti-inflammatory (best paleo estimate macronutrient distribution + no omega-6 + small amounts of supplemental omega-3) CR and ADF w/ optimal nutrition (lots of supplements). Denying yourself a major macronutrient in favor of reducing levels of a single protein seems kind of silly. Metabolic complexity can come back to haunt you. Its exactly the sort of thing Aubrey de Grey talks about when he speculates that its too hard with current technology to intervene in aging at the level of metabolism.

[xEva]

That's an interesting finding. I overlooked it till now. This quote from the Luigi Fontana study Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production confirms what Chupoman said above. Namely, a higher FFA level is interpreted by the body as the "starvation mode" and leads to the skeletal muscles ignoring glucose in favor of the tissues that cannot utilize FFAs. This is an old evolutionary response to "starvation" noted back in the 1970s in pioneering research by Cahill and Owen.

The key here is high level of FFAs:

http://www.ncbi.nlm....rticle_9118.pdf
Fasting serum free fatty acids were significantly higher in the CR group than in the WD group [WD = western diet, EX = exercise group of endurance runners].

Free fatty acids (mEq/L) :

CR group 0.72±0.35
EX group 0.59±0.18
WD group 0.51±0.20

In order to improve glucose tolerance what's needed is more carbs and less fat in the diet. Simply cutting out fat did the trick for me, when I was getting super high BG upon completion of a ~2 weeks fast. Of course this does not concern people on a ketogenic diet (other than knowing this fact, as Chupoman reminds us). Since CR people are not on a ketogenic diet, they would need to prevent into going into the "starvation mode" associated with high FFAs, which will drive the insulin resistance regardless of all other parameters. I am not saying that I'd know how to accomplish this on CR, only that this is an old metabolic fact. The EX group normally develops higher glycogen capacity, which delays their going into burning fat (and corresponding high level of FFAs).

The CR-IGT group was leaner and went into the starvation mode sooner, resulting in higher level of FFAs. I'd guess that the CR-IGT group is actually undernourished. IMO they need to up their calorie intake and add some exercise to improve their parameters.

Relevant quotes from the Fontana study:

Mean values for age, total body fat, and lean mass were not different between the two CR subgroups, whereas BMI was significantly lower in the CR-IGT subgroup than in the CR-NGT subgroup.

VO2max was markedly lower in the CR-IGT subgroup than in the CR-NGT subgroup.

.. our data suggest that severe chronic CR, in some individuals, may be associated with a relative peripheral insulin resistance mainly due to a low muscle mass with decreased capacity to take up glucose. [<-- that's related to glycogen capacity in endurance runners]

One possible explanation for the reduced glucose disposal following a glucose load in the CR practitioners may be a protective physiological adaptation to prevent hypoglycemia, which is considered part of the adaptive response to fasting.

...these individuals are in a state of “sensing” severe energy restriction.

[DR01D]

IMHO the reason that CR is associated with an increased risk of impaired glucose tolerance is well known to the medical community.

Low Muscle Mass Associated With Type 2 Diabetes Risk

The occurrence of insulin resistance, which leads to development of type 2 diabetes, is on the rise. Low muscle mass is known to increase this risk. The present study analyzes the role of this relationship in diabetes management. The possibility of improved glucose metabolism and sensitivity by improving muscle mass was worked out in this study. Interestingly, every 10 percent increment in the skeletal muscle index corresponded with 11 percent relative fall in insulin resistance and 12 percent dip in diabetes prevalence. A stronger relationship was noted in the nondiabetic population.

The Role of Skeletal Muscle in Glucose Transport, Glucose Homeostasis, and Insulin Resistance: Implications for Physical Therapy

Skeletal muscle has a fundamentally important role in the maintenance of normal glucose homeostasis and in regulating whole-body carbohydrate metabolism. In this review, we discuss the regulation of skeletal muscle glucose transport by muscular activity and inactivity. A large number of patients routinely seen by physical therapists exhibit some form of skeletal muscle insulin resistance. Therefore, we discuss how skeletal muscle insulin resistance can be localized to a relatively small muscle mass, or in other circumstances can affect a large proportion of the muscle mass leading to disturbances in whole-body glucose homeostasis.

Relative muscle mass inversely linked with insulin resistance and pre-diabetes

In this study, researchers examined the association of skeletal muscle mass with insulin resistance and blood glucose metabolism disorders in a nationally representative sample of 13,644 individuals. Participants were older than 20 years, non-pregnant and weighed more than 35 kg. The study demonstrated that higher muscle mass (relative to body size) is associated with better insulin sensitivity and lower risk of pre- or overt diabetes.

So it's not CR per se. It's the low muscle mass that's commonly associated with CR.

I've said it before and I'll say it again. People on CR should eat an extra couple of hundred calories each day and use it to build muscle mass. Our bodies depend on muscle for more than just physical strength.

Edited by DR01D, 23 September 2012 - 02:59 PM.

[DR01D]

In somewhat related news...

Diabetics look older

The study found that for people ages 50-70, those who had high blood sugar levels, either due to a poor diet or diabetes, consistently looked older than those with lower blood sugar levels. The findings revealed that for every 1 mmol/liter increase in blood sugar levels, subjects looked about five months older than their actual age. "The higher glucose people had, they started looking older," said lead researcher David Gunn in the release. "Diabetics looked older again, and they have had the worst exposure to high glucose levels."

So it's not a huge surprise that someone like Lou Ferigno looks years younger than his age. He eats a healthy diet and his large muscle mass keeps his blood sugar in the safe zone and protects him from Diabetes.

[Brett Black]

In somewhat related news...

Diabetics look older

The study found that for people ages 50-70, those who had high blood sugar levels, either due to a poor diet or diabetes, consistently looked older than those with lower blood sugar levels. The findings revealed that for every 1 mmol/liter increase in blood sugar levels, subjects looked about five months older than their actual age. "The higher glucose people had, they started looking older," said lead researcher David Gunn in the release. "Diabetics looked older again, and they have had the worst exposure to high glucose levels."

So it's not a huge surprise that someone like Lou Ferigno looks years younger than his age. He eats a healthy diet and his large muscle mass keeps his blood sugar in the safe zone and protects him from Diabetes.

The impact of glucose on perceived age in this study was extremely weak. I don't think it lends a very good hypothesis for explaining why someone may look younger than their chronological age(including Lou Ferigno):

"Non-diabetic subjects (n=569) were divided in three strata according to their glucose levels, and diabetic subjects (n=33; as a proxy of long-term hyperglycemic exposure) were included as a fourth stratum...........Perceived age was increased from 59.6 years (SE=0.3) in the first stratum to 61.2 years (SE=0.6) in diabetic subjects (p for trend=0.002).[1]"

So having outright diabetes only increased perceived age by a mere 1.6 years compared to those in the lowest glucose group.


REFERENCES

1: Noordam R, Gunn DA, Tomlin CC, Maier AB, Mooijaart SP, Slagboom PE, Westendorp
RG, de Craen AJ, van Heemst D; On behalf of the Leiden Longevity Study Group.
High serum glucose levels are associated with a higher perceived age. Age
(Dordr). 2011 Nov 20. [Epub ahead of print] PubMed PMID: 22102339.
http://www.ncbi.nlm....pubmed/22102339
http://www.springerl...8t8476q6433q44/

[InquilineKea]

IMHO the reason that CR is associated with an increased risk of impaired glucose tolerance is well known to the medical community.

Low Muscle Mass Associated With Type 2 Diabetes Risk

The occurrence of insulin resistance, which leads to development of type 2 diabetes, is on the rise. Low muscle mass is known to increase this risk. The present study analyzes the role of this relationship in diabetes management. The possibility of improved glucose metabolism and sensitivity by improving muscle mass was worked out in this study. Interestingly, every 10 percent increment in the skeletal muscle index corresponded with 11 percent relative fall in insulin resistance and 12 percent dip in diabetes prevalence. A stronger relationship was noted in the nondiabetic population.

The Role of Skeletal Muscle in Glucose Transport, Glucose Homeostasis, and Insulin Resistance: Implications for Physical Therapy

Skeletal muscle has a fundamentally important role in the maintenance of normal glucose homeostasis and in regulating whole-body carbohydrate metabolism. In this review, we discuss the regulation of skeletal muscle glucose transport by muscular activity and inactivity. A large number of patients routinely seen by physical therapists exhibit some form of skeletal muscle insulin resistance. Therefore, we discuss how skeletal muscle insulin resistance can be localized to a relatively small muscle mass, or in other circumstances can affect a large proportion of the muscle mass leading to disturbances in whole-body glucose homeostasis.

Relative muscle mass inversely linked with insulin resistance and pre-diabetes

In this study, researchers examined the association of skeletal muscle mass with insulin resistance and blood glucose metabolism disorders in a nationally representative sample of 13,644 individuals. Participants were older than 20 years, non-pregnant and weighed more than 35 kg. The study demonstrated that higher muscle mass (relative to body size) is associated with better insulin sensitivity and lower risk of pre- or overt diabetes.

So it's not CR per se. It's the low muscle mass that's commonly associated with CR.

I've said it before and I'll say it again. People on CR should eat an extra couple of hundred calories each day and use it to build muscle mass. Our bodies depend on muscle for more than just physical strength.

And did these studies control for the effects of people who had more muscle mass wasting with age than others? It could simply be that effect, especially since there are significant variations in muscle mass decline with age in aged populations.

[DR01D]

And did these studies control for the effects of people who had more muscle mass wasting with age than others? It could simply be that effect, especially since there are significant variations in muscle mass decline with age in aged populations.

It's my understanding that muscle is responsible for around 75% of the bodies glucose uptake. Google "Whole Body Glucose Uptake". So the muscle/diabetes correlation is not surprising.

Edited by DR01D, 02 October 2012 - 03:48 AM.

[Chupo]

Those with the physiological insulin resistance have the best markers of longevity. Why try to change it?

Look at their CRP and IGF-1:

[DR01D]

Those with the physiological insulin resistance have the best markers of longevity. Why try to change it?

Google insulin resistance and MCI, Dementia or Alzheimer's and you'll find plenty of info on why IR is dangerous when it continues over an extended period of time. There is also evidence that IR increases the risk of pancreatic cancer.

[Chupo]

This is physiological not pathological insulin resistance. It's not caused by an over abundance of fuel, just the opposite as explained above. They don't have high fasting blood sugar or hyperinsulinemia. Ketogenic diets, which cause the same type of peripheral insulin resistance are beneficial for MCI, Alzheimer's and other neurological diseases. As for pancreatic cancer, people with pathological IR have chronically elevated CRP, insulin and IGF-1 levels. That encourages cancer growth. These CRONies had low CRP and IGF-1.

[DR01D]

This is physiological not pathological insulin resistance. It's not caused by an over abundance of fuel, just the opposite as explained above.

As for pancreatic cancer, people with pathological IR have chronically elevated CRP, insulin and IGF-1 levels. That encourages cancer growth. These CRONies had low CRP and IGF-1.

In this video Paul McGlothin mentions that...

"We had some of our slimmest CR people, the past couple of years... this is kind of sad. They really limited calories a lot. Fasting glucose levels 200. Both died of pancreatic cancer."

I'm not convinced that CRONies with high glucose are in a special "physiological" state of insulin resistance. Insulin resistance is a risk factor for Pancreatic cancer and they both died from it.

DISCLAIMER: I'm a huge fan of calorie restriction and I have no doubt it increases healthspan and maybe even lifespan. I practice it every day and go to bed hungry almost every night. But when people take it to an extreme and burn off their muscle mass and live sedentary lifestyles it's a safe bet that they are setting themselves up for health problems. The human body was meant to be active and have a fair amount of muscle mass. Fighting evolution is usually a losing proposition. The reason that CR exists in the first place is because our evolution took place in a Malthusian world.

[Chupo]

Fasting BG of 200 is a problem! The cancer could have destroyed their beta cells resulting in such high fasting BG levels and also emaciation. Chicken or the egg, who knows?

[DR01D]

Fasting BG of 200 is a problem! The cancer could have destroyed their beta cells resulting in such high fasting BG levels and also emaciation. Chicken or the egg, who knows?

Pancreatic cancer is a rare condition.

SEER Stat Fact Sheets: Pancreas

Incidence Rate
Male: 13.8 per 100,000 men (1 in 7,246)
Female: 10.8 per 100,000 women (1 in 9,259)

However when you mess with evolution you are bound to get unexpected results.

Jack LaLanne made it to 96 and had amazing health until his last couple of years.

Check out his diet.

He ate two meals a day and avoided snacks. His breakfast, after working out for two hours, consisted of hard-boiled egg whites, a cup of broth, oatmeal with soy milk and seasonal fruit. For dinner he and his wife typically ate raw vegetables and egg whites along with fish.

Jack was living a CR lifestyle except he included lots of strength training and plenty of daily activity. He was generations ahead of everyone around him.

The human body is very efficient. A healthy man can slowly pack on muscle with strength training and just a 100 calorie daily surplus. You need very little extra protein as well. Look how big weightlifters get in prison. They get enormous on a diet of junk, processed carbs and bologne sandwiches.

Edited by DR01D, 03 October 2012 - 08:56 PM.

[dz93]

GMO foods contribute to a rise in diabetes.

My suggestion with CR is to make sure you get all the vitamins, minerals, and nutrients a human needs to be fully healthy. That's common sense that I'm sure all calorie restricted people know about. The other even more important thing is getting rid of GMO foods. They've been linked with multiple diseases and illnesses and I can't believe this stuff is still on the market and that no one knows that 90% of the soy in the US is GMO. Now look on the label of a food product. Does it have soy in it? Is it from a big corporation? Then it's GMO.

[xEva]

This is physiological not pathological insulin resistance. It's not caused by an over abundance of fuel, just the opposite as explained above. They don't have high fasting blood sugar or hyperinsulinemia. Ketogenic diets, which cause the same type of peripheral insulin resistance are beneficial for MCI, Alzheimer's and other neurological diseases. ...

I disagree. It is a serious problem for someone who is *not* on a ketogenic diet. People on a ketogenic diet will experience this rise in glucose only when they eat carbs (more than their minimum), which is a rare occasion for them. A cronie, on another hand, will have this rise each time he eats. This was a problem for me after a fast (this and high morning fasting glucose) and I had to cut all fat out for about 2 weeks, until the metabolism came to normal.

I agree with DRO1D:

I'm not convinced that CRONies with high glucose are in a special "physiological" state of insulin resistance.

High sugar is a bad thing, worse if it happens often. It sounds like the under-nourished and under-exercised cronies are not doing it right. There is a small group on a Russian fasting forum who claim that the more they are active physically, the less food they require to feel energetic. I too experienced those paradoxical states, in cold months of the year. Movement in cold weather feels like a meal and makes you look good, rosy cheeks and bright eyes

[Chupo]

Paul McGlothin's glucose tracking report showing how teaser carbs and exercise work to keep blood glucose low:



Source

[mikeinnaples]

Fasting BG of 200 is a problem! The cancer could have destroyed their beta cells resulting in such high fasting BG levels and also emaciation. Chicken or the egg, who knows?

I agree that anyone with a fasting BG of 200 is doing something wrong lifestyle wise, CR practitioner or not.

[xEva]

A fasting blood glucose level over 125 mg/dl indicates diabetes. 200 is a raging diabetes. I watched the video with Paul McGlothin again. He speaks about those 200 fasting BG levels in the context of very low calories but, apparently, rather high protein. This contrasts with Steve Jobs who too died of pancreatic cancer while living for most of his life on a low protein, vegan diet -?

The other thing Paul said, also at the end, was that niacinamide is not a good vitamin to take when starting CR, because it downregulates sirtuins. So I looked around and moderators here (maxwat and niner) claim that the quantities normally taken have no relevance in vivo. Which way is it?

Edited by xEva, 01 February 2013 - 12:13 AM.

[xEva]

Re Paul's remark about niacinamide and CR, the answer is here: http://www.longecity...denicotinamide/

[Kevnzworld]

If practicing CR is a healthy endeavor one would not expect to see impaired glucose tolerance. The explanation that the low muscle mass is the culprit, should be a signal for how unnatural CR is. I wonder how our CRON friends will ultimately deal with issues like sarcopenia as they age, and possible loss of bone integrity? Michael Rae reported in 2007 that he is six feet tall and weighed 115 lbs. He was 37 at the time. It only becomes more difficult to maintain muscle mass as the years progress, especially as hormone production declines.
His diet as reported in a 2007 interview contained enough fiber that one wouldn't normally expect post prandial spikes, especially from eating salads.
I believe in moderation. I consume a 2000 calorie diet, more or less. I don't eat red meat, and I attempt to consume most of my carbs in the form of vegetables and whole grains. My weight is 147 , and I weigh 5'9". I have low CRP, homocysteine, HbA1C and insulin levels.
( without extreme CR ). My fasting glucose is in the low 80's and my post prandial, when I test it is 95-105.
I find it difficult to believe that restriction beyond what I practice will lead to a longer and more importantly a healthier longer life.

[Chupo]

Were these CRONies frutarian perhaps?

About pancreatic cancer,: It's only observational but...

A significant association was found with fruit and juices intake (1.37; 1.02, 1.84; P for trend = 0.04) but not with soda intake.

http://ajcn.nutrition.org/content/86/5/1495.full

This is a rebuttal to McDougall's lecture on Job's cancer:
http://www.psycholog...1301/veganthink

[xEva]

Were these CRONies frutarian perhaps?

I doubt they were frutarians, because Paul spoke about them in the context of high protein and 'very low calories'. Maybe they were diabetic (having fasting BG at 200 certainly qualifies) and they were trying to control it by limiting carbs -? This is just a speculation on my part. Then there are different types of pancreatic cancer, one is very aggressive and another is curable when addressed on time. Steve Jobs had the second, more benign type.

If practicing CR is a healthy endeavor one would not expect to see impaired glucose tolerance. The explanation that the low muscle mass is the culprit, should be a signal for how unnatural CR is. ...Michael Rae reported in 2007 that he is six feet tall and weighed 115 lbs....

I think this underscores that CR is not as simple as eating less and tracking your diet with the right software. Or maybe it is not for everyone -?

I thought MR was 135 -? 115 is way too low for 6 ft. It gives BMI of 15.6. Was he really that thin? When fasting, reaching BMI of 15 is the call to break the fast without delay.

[Kevnzworld]

Quote from the Michael Rae interview, both question and answer :

" Now, you are six feet tall and weigh 115 lb. That sounds really slender.
But I was already really slender.
I read that you were about 140 lb. to start with.
Yeah. If you start off skinny you've definitely got a disadvantage there."
http://www.macleans....5_139289_139289

He is now 43 and has issues with insulin and glucose. Forced cachexia and living so close to the edge can not be healthy longer term. Most people struggle to retain muscle as they age.
I prefer to supplement with what some people call CR mimetics, ( something MR doesn't believe in ) and eat a more moderate, balanced diet.

[xEva]

Wow. What's his weight now? And I am surprised that he would develop issues with glucose and insulin. I thought he monitored his BG with a meter, like Paul does. 115 lbs at 6 ft is really extreme.

[mikeinnaples]

I am a hair under 6'1 and this morning I weighed in at 184lbs. I am not built like a body builder because of how I train, but instead, more like boxer. I am in the 9-10% actual body fat range, I am sure that I could lose every pound of muscle on my body and still not get down to that low of a weight before literally dying of starvation. That is crazy low and I cant see how it can be healthy.

[DR01D]

If you're eating 1500 calories per day you probably aren't consuming enough energy to have a lifestyle that's more than sedentary. That's probably not good for insulin sensitivity.

sciencedaily: Long, Low Intensity Exercise May Have More Health Benefits Relative to Short, Intense Workouts

According to the study, being active simply by standing or walking for long periods of time significantly improved insulin levels compared to both a strictly sedentary lifestyle, and one in which participants were largely sedentary except for an hour of exercise each day. The study concludes that when energy expenditure is equivalent, longer durations of low-intensity exercise may offer more benefits than shorter periods of intense activity.

You're better off eating a few hundred extra calories per day and using it for exercise/work.

Edited by DR01D, 14 February 2013 - 03:16 AM.

[The Immortalist]

Here's the first study that showed impaired glucose tolerance in some calorie restricting humans(including members of the CR Society mailing list):

1. Age (Dordr). 2010 Mar;32(1):97-108. Epub 2009 Nov 11.

Effects of long-term calorie restriction and endurance exercise on glucose
tolerance, insulin action, and adipokine production.

Fontana L, Klein S, Holloszy JO.

Washington University School of Medicine, St. Louis, MO 63110, USA.
lfontana@dom.wustl.edu

Calorie restriction (CR) slows aging and is thought to improve insulin
sensitivity in laboratory animals. In contrast, decreased insulin signaling
and/or mild insulin resistance paradoxically extends maximal lifespan in various
genetic animal models of longevity. Nothing is known regarding the long-term
effects of CR on glucose tolerance and insulin action in lean healthy humans. In
this study we evaluated body composition, glucose, and insulin responses to an
oral glucose tolerance test and serum adipokines levels in 28 volunteers, who had
been eating a CR diet for an average of 6.9 +/- 5.5 years, (mean age 53.0 +/- 11
years), in 28 age-, sex-, and body fat-matched endurance runners (EX), and 28
age- and sex-matched sedentary controls eating Western diets (WD). We found that
the CR and EX volunteers were significantly leaner than the WD volunteers.
Insulin sensitivity, determined according to the HOMA-IR and the Matsuda and
DeFronzo insulin sensitivity indexes, was significantly higher in the CR and EX
groups than in the WD group (P = 0.001). Nonetheless, despite high serum
adiponectin and low inflammation, approximately 40% of CR individuals exhibited
an exaggerated hyperglycemic response to a glucose load. This impaired glucose
tolerance is associated with lower circulating levels of IGF-1, total
testosterone, and triiodothyronine, which are typical adaptations to
life-extending CR in rodents.

PMCID: PMC2829643
PMID: 19904628 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....pubmed/19904628
http://www.ncbi.nlm....les/PMC2829643/
http://www.ncbi.nlm....rticle_9118.pdf

Cut the carbs out of the diet and problem solved?

[The Immortalist]

I am a hair under 6'1 and this morning I weighed in at 184lbs. I am not built like a body builder because of how I train, but instead, more like boxer. I am in the 9-10% actual body fat range, I am sure that I could lose every pound of muscle on my body and still not get down to that low of a weight before literally dying of starvation. That is crazy low and I cant see how it can be healthy.

Everyone has a different bone structure. You simply have bigger and hence heavier bones then MR.

[tunt01]

This is an interesting thread (which I am reviving somewhat).  Other than eating more calories/protein.  It seems like these IGT CR folk would need to live as diabetics, if they have become too frail.

 

What are some strategies at reversing this IGT and/or recovering pancreatic function that has been lost due to protein too low?  Anyone have thoughts?