Freethought & Rationalism Archive

ps418 · 05-01-2003, 07:02 AM

A new study in the PNAS shows that mice that fast one day and feast the next derive some of the same health benefits seen in mice on very low calorie diets while maintaining their weight. Even when total calories are the same, the fast-feast mice do better than the eat-everyday mice. In other words, it may be possible to get the benefits of a caloric restriction diet without actually restricting calories. The abstract of the paper doesn't say whether they also exhibit the greater life span of the caloric restriction mice, however.

Quote:

Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that when C57BL/6 mice are maintained on an intermittent fasting (alternate-day fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.

Anson et al, Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. PNAS published April 30, 2003, 10.1073/pnas.1035720100.

Press Release - New Scientist

Patrick

Nuno Figueira · 05-01-2003, 03:19 PM

Interesting. I'm particulary curious about the how big is the role of insulin levels in this issue. Researchers have said that the two most important factors are low insulin levels and low body temperature. Low insulin levels can be attained without calorie restriction but lower body temperature is probably more of a side effect of a reduced metabolic rate so that's more tricky. Unfortunatelly it will take a while till they can get results from studies performed in humans.

repoman · 05-05-2003, 10:10 AM

Personally, even if alternate day fasting was show to be effective I would still go for standard calorie restriction - just for the steady habit. But I think that animals our size would have more side effects with alternate day fasting than mice.

I thought the point of CR was to delvier the fuel more closely in a "just in time" manner taht doens't have to work twice as much. You don't have to pend energy and excess insulin locking up the sugars or making them into fats. Then you don't have to use glucagon, or god fordbid, lots of cortisol to release the sugars.

Wouldn't your hormones be tweaked on the transiton from fasting to eating? and what about the levels water soluble vitamins and antioxidants? wouldn't they be low when you start eating again, thereby leading to more free radical damage?

05-05-2003, 02:07 PM

It's my understanding that on any 'starvation' diet, the body tends to break down muscle disproportionately to body fat for fuel, making a low calorie or starvation diet counter-productive to what most people wish to achieve.

repoman · 05-05-2003, 03:39 PM

RGI's post got me to think about the definition of calorie restriction. I think I remember that for laboratory animals they first let them eat as much as they wanted, then they let them eat like only 60-70% of that amount of food. But this name gives the actual practice of this technique a spartan tone that it doesn't deserve.

A more basic form of CR is dropping from a supersized meal to a more sensible size. I think taht for humans it is important to not constantly eat large amounts of high carb (especially fast acting ones like bread and potatoes) meals with low levels of meat, fat, fiber or veggies that buffer those carbs. They say that the dose makes the poison.

JGL53 · 05-05-2003, 07:15 PM

Repoman, you are correct - that exactly is slowly beginning to be the new consensus among scientists who actually do research in the area of human diet. The type of food (or calories) one consumes can and does make a difference in the total food one consumes, to wit:

Too much a per cent of high glycemic carbohydrate (low fiber) foods can and does induce an unnaturally high production of insulin, causing an eventual too great a drop in blood sugar, which causes unnatural hunger, leading to binging or 'over-eating', which can be in turn cause obesity and Type II diabetes.

Reactive hypoglycemia is beginning to be a recognised medical problem. I have this, and the only way I can prevent 'attacks' is by getting most of my calories from protein and fat, and getting a lot of my carbs from green, leafy, non-starchy vegetables.

ps418 · 05-08-2003, 06:47 AM

There is an article in today's issue of Nature reporting on the discovery of a gene in yeast, PNC1, that is upregulated by caloric restriction and plays a major role in caloric restriction-induced lifespan extension. I didn't know that caloric restriction increases lifespan in yeast. Their are homologous genes in mice and humans, and though the same systems are more complex in mammals, it is possible that a therapy that upregulates the homologous human gene(s) could produce some or all of the beneficial effects associated with caloric restriction.

Quote:

Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

Anderson et al, Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423, 181 - 185 (2003).

From the Press Release:

Quote:

BOSTON, MA-- Researchers at Harvard Medical School (HMS) have discovered that a gene in yeast is a key regulator of lifespan. The gene, PNC1, is the first that has been shown to respond specifically to environmental factors known to affect lifespan in many organisms. A team led by David Sinclair, assistant professor of pathology at HMS, found that PNC1 is required for the lifespan extension that yeast experience under calorie restriction. A yeast strain with five copies of PNC1 lives 70 percent longer than the wild type strain, the longest lifespan extension yet reported in that organism. Their findings are reported in the May 8 Nature.

The PNC1 protein regulates nicotinamide, a form of vitamin B3. Sinclair's group previously found that nicotinamide acts as an inhibitor of Sir2, the founding member of a family of proteins that control cell survival and lifespan. Sir2 extends lifespan in yeast by keeping ribosomal DNA stable. PNC1 converts nicotinamide into nicotinic acid, a molecule that does not affect lifespan. In doing so, it keeps nicotinamide from inhibiting Sir2, allowing the yeast to live longer.

The finding implies that lifespan is not simply dependent on accumulated wear and tear or metabolism, as some researchers have suggested, but is at least partly controlled by an active genetic program in cells--one that could theoretically be boosted. "In contrast to the current model, we show that the lifespan extension from calorie restriction is the result of an active cellular defense involving the upregulation of a specific gene," Sinclair said.

Patrick

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05-01-2003, 03:19 PM	#2
Nuno Figueira Junior Member Join Date: Mar 2003 Location: Portugal Posts: 92	Interesting. I'm particulary curious about the how big is the role of insulin levels in this issue. Researchers have said that the two most important factors are low insulin levels and low body temperature. Low insulin levels can be attained without calorie restriction but lower body temperature is probably more of a side effect of a reduced metabolic rate so that's more tricky. Unfortunatelly it will take a while till they can get results from studies performed in humans.

05-05-2003, 10:10 AM	#3
repoman Veteran Member Join Date: Aug 2001 Location: Seattle Posts: 2,280	Personally, even if alternate day fasting was show to be effective I would still go for standard calorie restriction - just for the steady habit. But I think that animals our size would have more side effects with alternate day fasting than mice. I thought the point of CR was to delvier the fuel more closely in a "just in time" manner taht doens't have to work twice as much. You don't have to pend energy and excess insulin locking up the sugars or making them into fats. Then you don't have to use glucagon, or god fordbid, lots of cortisol to release the sugars. Wouldn't your hormones be tweaked on the transiton from fasting to eating? and what about the levels water soluble vitamins and antioxidants? wouldn't they be low when you start eating again, thereby leading to more free radical damage?

05-05-2003, 02:07 PM	#4
Robert G. Ingersoll Guest Posts: n/a	It's my understanding that on any 'starvation' diet, the body tends to break down muscle disproportionately to body fat for fuel, making a low calorie or starvation diet counter-productive to what most people wish to achieve.

05-05-2003, 03:39 PM	#5
repoman Veteran Member Join Date: Aug 2001 Location: Seattle Posts: 2,280	RGI's post got me to think about the definition of calorie restriction. I think I remember that for laboratory animals they first let them eat as much as they wanted, then they let them eat like only 60-70% of that amount of food. But this name gives the actual practice of this technique a spartan tone that it doesn't deserve. A more basic form of CR is dropping from a supersized meal to a more sensible size. I think taht for humans it is important to not constantly eat large amounts of high carb (especially fast acting ones like bread and potatoes) meals with low levels of meat, fat, fiber or veggies that buffer those carbs. They say that the dose makes the poison.

05-05-2003, 07:15 PM	#6
JGL53 Veteran Member Join Date: Jul 2002 Location: Outer Mongolia Posts: 4,091	Repoman, you are correct - that exactly is slowly beginning to be the new consensus among scientists who actually do research in the area of human diet. The type of food (or calories) one consumes can and does make a difference in the total food one consumes, to wit: Too much a per cent of high glycemic carbohydrate (low fiber) foods can and does induce an unnaturally high production of insulin, causing an eventual too great a drop in blood sugar, which causes unnatural hunger, leading to binging or 'over-eating', which can be in turn cause obesity and Type II diabetes. Reactive hypoglycemia is beginning to be a recognised medical problem. I have this, and the only way I can prevent 'attacks' is by getting most of my calories from protein and fat, and getting a lot of my carbs from green, leafy, non-starchy vegetables.

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