Calorie Restriction and Life Span

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WARNING: this is going to be a doozy of a post.

The topic of calorie restriction to increase one’s lifespan has grown in popularity in recent years and to be honest, I am not falling for it. First: we don’t necessarily know for sure whether or not it works. Sorry weirdos, but just because there have been a bunch of studies performed on rats doesn’t mean it correlates to humans. Second: as the study below showcases, the later one starts restricting calories in life, the less impact it will have on life span. So unless we want to starve our children their entire lives, I don’t see this fad catching on. Third: is it really worth it to live your life in constant hunger, cold (decreased metabolism lowers body temperature), and with very low energy levels only to increase your life by a few years at best? Seems a bit harsh in my eyes. And who says those extra years are going to be “high quality” years. No one really knows the long term health risks of chronic caloric restriction, unless we want to count the Olsen twins as proof. Oh snap!

Olsen Twins

Below is a research review done by Lyle McDonald a few months ago concerning calorie restriction (CR) and life span. I thought it was very interesting and figured I would share it with the masses as well. Enjoy nerds…..(wink).

Research Review

Speakman JR and Hambly C. J Nutr. 2007 Apr;137(4):1078-86. Links

Starving for Life: What Animal Studies Can and Cannot Tell Us about the Use of Caloric Restriction to Prolong Human Lifespan.

Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction. The benefits of CR, however, decline as the age of onset of treatment is delayed. Modeling these impacts suggests that if a 48-y-old man engaged in 30% CR until his normal life expectancy of 78, he might increase his life expectancy by 2.8 y. Exercise and cold exposure induce similar energy deficits, but animals respond to these energy deficits in different ways that have a minor impact on lifespan. Measurements of animal responses when they cease restriction indicate that prolonged CR does not diminish hunger, even though the animals may have been in long-term energy balance. Neuroendocrine profiles support the idea that animals under CR are continuously hungry. The feasibility of restricting intake in humans for many decades without long-term support is questionable. However, what is unclear from animal studies is whether taking drugs that suppress appetite will generate the same impact on longevity or whether the neuroendocrine correlates of hunger play an integral role in mediating CRs effects.

My comments: Excuse me a bit of lofty prose here…

For literally centuries, man has looked for ways to extend life or achieve immortality. From drugs to anti-oxidants to various other approaches, escaping the breaths of death has been a common human goal. In recent years, one approach has come to the forefront as not only having the potential to increase lifespan but actually having been shown to do so in most models studied (apparently houseflies are an odd exception).

That approach is called caloric restriction (CR) and is sometimes differentiated from your basic calorie restricted diet by adding the rider of caloric restriction with optimal nutrition (CRON) with the idea of CRON being a reduction in total food intake while still ensuring sufficient/optimal intake of required nutrients.

Of course, by needs, most of the research on CR has been done in animal models since it’s not feasible to track humans over their lifespan to see what effect CR will have. However, CR has been studied in humans under more short-term conditions, looking primarily at various health parameters as an end result. For example, the Biosphere II experiment ended up being a 2 year CR model when the food supply failed and this allowed researchers to examine a number of effects of CR on human metabolism.

And before addressing this week’s study, I want to make that very clear distinction: there are two possible effects of CR. The first, and the one that the paper this week addresses is an actual increase in lifespan. As the paper points out, in some studies, an increase in 50% of average lifespan has been observed in some animal models. Applied to humans, CR might be expected to increase lifespan from an average of 78 to 116 years in men and 83 to 124.5 years in women.

However, an additional potential impact of CR is on overall health and even if CR fails to increase human lifespan, it could still have potential benefits on various health parameters (such as insulin levels and cancer risk). That second aspect of CR is not discussed in this paper but may be of as much importance.

One of the questions, and the one this paper addresses is what animal studies can and cannot tell us about the impact of CR on human metabolism.

The first issue addressed is what level of restriction is needed with 50% of normal intake generating the largest impact on lifespan. Because of the intakes of the control animals, this actually ends up being a 65% reduction from normal food intake. This level of restriction is required to get the maximum 50% increase in lifespan. Smaller reductions, such as 30% below normal, generate only a 20% increase in lifespan. Think about those numbers for a second. A male with a predicted maintenance of 2700 calories/day would be expected to consume 1350 cal/day for extended periods, a female with an 1800 cal/day maintenance would have to subsist on 900 calories per day for extended periods to gain benefits of CR.

The next topic discussed had to do with when restriction should begin for optimal results. The paper points out that almost all studies of CR in rodents and mammals occur very early in life, essentially after they are weaned (basically, child mice and rats). Basically, they are CR for their entire lives. Studies where CR is instituted later in life typically show much lesser impact with mortality rate frequently being identical to non CR animals.

Clearly, early onset CR has little relevance to humans who are unlikely to restrict their caloric intake for their entire lives. Rather, individuals (typically as they get older) become more interested in CR. An important question is then what benefits might occur if CR is started later.

Tangentially, and interestingly, the paper notes that elderly often begin eating less (often due to the onset of disease) and a loss of weight tends to be associated with higher mortality; nutritionists often focus on trying to keep bodyweight from dropping in these individuals.

In any case, plotting the relationship between the impact of CR on lifespan and when it is started, the researchers show a linear decline in impact as age goes up. putting this into table form, assuming that the animal research applies to humans, they show the following

Age at onset Time on restriction 15% restriction 30% restriction

15.6 years 62.4 years 5.6 years 11.2 years

23.4 years 54.6 years 4.7 years 9.4 years

31.2 years 46.8 years 3.3 years 6.5 years

39 years 39 years 2.4 years 4.8 years

46.8 years 31.2 years 1.4 years 2.8 years

54.6 years 23.4 years .25 years .3 years

62.4 years 15.6 years 0 years 0 years

Age of onset is when CR is begun, time on restriction refers to how many years the subject would have to restrict calories. The last two columns show the potential impact on lifespan of either 15% or 30% caloric restriction. For example, if someone began CR at 39 years old, and restricted their food intake by 15% for the next 39 years, they could expect an increase in lifespan of 2.4 years. If they could handle a 30% reduction in food intake, they might get 4.8 years extra lifespan. By the time folks are in their 50’s, CR has essentially zero impact on predicted lifespan. Again, assuming that the animal research holds. It’s possible that CR will be more effective in humans, just as its possible that it won’t even be as effective as in animals.

Another important question regarding CR has to do with hunger and whether or not it ever goes away with chronic CR (tangentially: this is also a question of importance to anyone trying to maintain an extremely reduced bodyfat level). To test this, the researchers placed mice on 20% CR for 50 days (equivalent to roughly 2.5 years in humans) and then allowed them to eat ad libitum to see if appetite had decreased. Quite simply, it hadn’t and the animals ate like crazy when given access to food. Unpublished data on their neuroendocrine profiles indicated that the animals remain physiologically hungry throughout the CR period.

The next point addressed by the researchers had to do with the mechanisms by which CR work which I’m not going to go into in detail. However, the researchers make an important note regarding the impact of CR on energy levels and exercise along with differences in the most common causes of death between rodents and humans. In rodents, the major cause of death is cancer whereas in humans it is cardiovascular disease. Additionally, while exercise regularly is shown to have benefits for humans (in terms of health), this is not the case for animals.

They mention that the reductions in activity that typically occur with CR (they anecdotal reports of humans involved in CR of low-energy, along with chronic cold) could be detrimental to humans (but not to rodents); reducing exercise due to low energy levels might predispose humans to higher risk for cardiovascular disease. At the same time, primate studies of CR suggest improvements in markers of cardiovascular function. Additionally, one study of CR groups suggest a much improved cardiovascular risk profile; however that group was also engaged in regular exercise and were much leaner. Whether the impact on risk was due to exercise/low bodyfat or CR per se is impossible to determine.

Finally, the paper addresses what the animal studies can’t tell us about CR. The first issue is whether or not the extent and duration of CR required to generate effects in humans is even feasible in humans. That is, in animal models it’s simple to institute CR, the animals eat what you give them. Outside of small groups, it seems unlikely for the average human to voluntarily reduce food intake by 20% or more for upwards of 40 years, especially if the benefit is a mere 4-5 years increase lifespan.

Another issue is whether drugs that generate weight loss (usually through blunting appetite) have the same impact as CR per se. Given that some of the effects of CR seem to be mediated through the same neuroendocrine effects that make the animals hungry, drugs that alter normal neuroendocrinology may not generate the same effects. Interestingly, the researchers mention surgical intervention as being a potential way of ensuring lifetime adherence to CR protocols.

Finally, they address whether it’s feasible (beyond issues of hunger) for humans to engage in CR when they have to live in the real world. That is, it’s one thing to have rodents confined to a cage who eat what they are given engage in prolonged CR. Even there, studies in rodents suggest a loss of lean body mass. While this isn’t detrimental to a caged animal, a loss of functional mass would be detrimental to humans who have to function to survive. An additional issue would be immune function as rodents are kept in a pathogen free environment; however studies of CR suggest an increase in immune function.

Summing up: assuming that the animal research can be applied to humans, it would appear that CR is unlikely to have a large impact on human lifespan per se (again, this is outside of potential health benefits) even if it is instituted quite early. Since this is unlikely, and most individuals engaging in CR are older in the first place, it’s interesting to note that the predicted impact on total lifespan is small approaching negligible. Thirty years of chronic hunger, cold and low energy levels might net a 40 year old an extra couple of years of life at best. This seems rather unreasonable to me.

Once again, an issue not addressed in this review is the impact of CR on various health parameters. However, at least some research suggests that other approaches (such as intermittent fasting or every other day fasting, or exercise to generate the caloric deficit) may generate the same effects as CR per se and may be much more reasonable for long-term application.

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Comments for This Entry

  • Roberto Aguilar

    "(such as intermittent fasting or every other day fasting, or exercise to generate the caloric deficit) may generate the same effects as CR per se and may be much more reasonable for long-term application." Ive always been fascinated with the apparent benefits of fasting for early cultures in the world. Are there any theories behind what are their real benefits beyond the immune system regeneration of longer fasts?

    December 29, 2014 at 9:27 pm | Reply to this comment

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