Caloric Restriction Diet

Goal: To bring caloric restriction into the discussion about healthy lifestyle choices and to explore options and strategies for implementing it.

Motivation: Live longer, healthier lives.

What is caloric restriction?

The basic definition is that CR is a diet in which you restrict your intake of calories without causing malnutrition. The intake of calories is restricted relative to your unrestricted, normal intake. Effects can be seen with as little as 10-25% 1 reduction in humans and laboratory tests typically induce ~40% reduction of calories. 8,5

Why should we consider caloric restriction?

  • Reduce the risk of atherosclerosis in humans. 1 , 5
  • Reduce the risk of and prevent cancer. 2, 17
  • Extend the maximum life span in humans up to 30-40%. 3, 8
  • Extend the quality of your extended lifespan. 8,5
  • Improves blood pressure and diastolic function. 4, 16
  • Greatly reduces the risk of diabetes. 5,6, 9
  • Lose weight. 7
  • Protect against Alzheimer’s and neurodegenerative diseases. 8,10
  • Shown to grant superior cognitive abilities in lab animals. (May make you smarter!) 11, 12, 13

Why should we not consider caloric restriction?

  • People on caloric restriction obtain a very low body mass index , which may be considered “underweight” and can lead to other health complications. 1
  • Potential loss of libido.  15
  • Hypotension. 1
  • Menstrual irregularities.
  • Infertility.
  • Bone thinning.
  • Osteoporosis.
  • Sensitivity to cold temperatures. 18
  • Loss of strength and stamina.
  • Slower wound healing.
  • Depression.
  • Loss of muscle mass.
  • (The risks of CR as less well documented, but it’s safe to say that they may be a problem to some people.)

Why may caloric restriction work in humans?

The answer to this may be less grounded in fact and science than in theory and speculation, but these are the ideas I’ve explored and the possible conclusions they suggest. Research definitely points to an increase in maximum life span or beneficial health effects with CR in many animals (including primates). There are changes in gene expression induced by the perceived starvation condition in cells. These changes make me think that our body’s response to CR is sort of a “program” that our bodies load up, as opposed to an unintended or random consequence of a starvation diet.

To enforce the previous statement, I present the idea that in starvation conditions, it is more beneficial to survival if you had longer lifespans. As a thought experiment, if we place two populations in conditions with low energy supply (food), where one of them lives to a significantly older age than the other, we can see that the population that spends less energy on reproduction in these tough times will have more energy later for reproduction. Reproduction is an energy intensive process since children need to grow and use more energy than adults who have stopped growing. It seems plausible that the shorter lived population will need to reproduce more often than the longer lived population in order to maintain their society, whereas the longer lived population can conserve more energy by reproducing less often to maintain their population.  The conclusion of the thought experiment is that if your society has more energy available, they will feel less evolutionary pressure to have longer lifespans. But if a population evolves in circumstances where food is hard to come by (which some parts of our evolutionary history must have been in), it may make sense for humans to have evolved a genetic program to extend lifespan in those situations.

Aside from this theory and many animal tests that suggest CR may work in humans, there is some pretty solid evidence in a non laboratory setting that CR works in humans as well. One example is Okinawa. 14  A study showed that their normal diet contains ~40% fewer calories when compared with the normal American diet. They eat mostly nutrient dense foods. (veggies, fruits, grains, soy, fish, and seaweed). And interestingly, their average lifespan as a population is longer than their American counterparts. (Granted, it could also just be the effect of a more balanced diet and not necessarily a lack of calories.)

Is caloric restriction good for me? Should I consider a CR diet?

This  is probably the most tricky question as I believe it is case dependent. If your occupation is the world’s bodybuilding champion or if you are still young and growing, I would suggest avoiding a CR diet simply because it may do more harm to your desired occupation or future lifestyle than good. If you are a middle aged desk worker with a desire to make it to the singularity or your genetics make you prone to diabetes and cancer, then CR may be very beneficial. However, there are always those of us in between these extreme categories, where we may want to benefit from CR, but aren’t willing to decrease the quality of our lives to do so. That is the category that I fall into. I enjoy sports, food, and I like to hope that I’m still in my growth phase, yet I have a desire to age gracefully and live as full of a life as I possibly can. Is there a way that I can have the best of both worlds? It doesn’t seem that there is a clear cut answer to that question yet, but I will do my best to come up with one in the following paragraphs or future posts.

What can I do to “have it all?” What are some alternative methods to CR?

  • Reduced degree of CR. Restricted caloric intake of between 8-25%, rather than the laboratory 40% has been shown to also have an effect on our bodies. The benefits are clearly seen even at these less restricted levels. 19 Although it doesn’t “maximize” the benefits, CR seems to work on a continuum.
  • Every other day feeding (EOD). Basically what it sounds like. If you restrict your calories every other day (but keep your fluids and nutrients). It has been shown in lab mice to have similar effects to being on CR continuously. 20, 21 The mice will eat twice as much as normal on non-fasting days, so the total caloric intake stays on average the same. It is thought that the cells will be stimulated to make beneficial changes as if they were on caloric restriction on those fasting days.22 It’s sort of like spiking in some longevity signals into your cells every other day.  It keeps them on their toes.
  • Mimetic. These are typically known as anything you can take, inject, or eat that can mimic the effects of CR without having to restrict your eating. Some of more well known compounds as of this article’s date are Resveratol, metformin, rapamycin. 23
    • Resveratrol is that compound that you always hear about in red wine. It has been shown in many lab tests to induce a genetic profile similar to that of caloric restriction. There have been very few human tests to date, but at least one study conducted by Sirtris verifies its beneficial effects. However, the doses of resveratrol are between three to five grams per day! 24  To put that in perspective, a glass of red wine contains only miligrams of resveratrol. (thousands of times less!) Also, the study by Sirtris was never published, making me think that they have something to hide. Sometimes you have to question studies from entities that have a financial stake in the result.
    • Metformin is used as an anti-type II diabetes medication, however, it has also been shown to extend lifespan in mice. 25 This sort of makes sense since type II diabetes can be caused by a very bad diet, almost like the polar opposite of a nutrient rich, low calorie diet such as would be required for CR.
    • Rapamycin is a drug normally used to prevent organ rejection during transplantation. It has been shown to increase lifespan in yeast and acts in the TOR signaling pathway, which is believed to be involved in the aging pathway. 26

Mimetics commentary:

Due to the lack of concrete evidence for beneficial effects of any of the popular CR mimetics, I tend to stray away from them. It seems unlikely that a single molecule that most likely didn’t evolve alongside humans could have such a targeted and specific effect on anti-aging pathways. Plus, the amounts of these drugs needed would make their daily use prohibitively expensive, especially for a graduate student like myself. In addition, I have personally taken resveratrol supplements for a shorter period of time and I found that when taken at a dosage of about 0.5g per day (and starting at ~200mg, working my way up), I started feeling very nauseous early in the morning after I had taken it, almost to the point of vomiting. Perhaps this was the brand that I got, but for some reason it didn’t agree with me.


I have concluded that the benefits of CR is something I want to take advantage of, at least partially. I don’t care to restrict my diet by 40%, but I find it fairly easy to reach the ~10-20% mark at least every other day. Once I planted the idea that eating less is actually better for my health, I started to actively associate the feeling of hunger with health and longevity. It may sound kind of crazy, but I’ve found that you can trick your brain pretty easily, even if you’re aware that you’re doing it. (I’ve also used this trick to get myself to enjoy eating broccoli.) Eventually, after telling myself for long enough that I “enjoyed the feeling of hunger”, it didn’t really bother me as much. I am still able and willing to go out to my favorite restaurant or pig out at a party every once in a while, but for those slow days where I have no social reason to pig out, I am able to stimulate my cells by giving them a dose of partial starvation to keep them in shape.

On these days I have to also worry about reduced nutrient intake. I try to remedy that problem with nutrient dense smoothies that consists  of a scoop of a vegetable/fruit powder, milk, a scoop of a fiber supplement, some food replacement powder, and a scoop of cocoa to mask the flavor (which works surprisingly well). If it’s still really bad, I sometimes add flavored protein powder. I gulp this down, which is the equivalent of eating a super healthy meal full of fruits, vegetables, fiber, and protein. In addition, I also take fish oil for my omega 3’s, vitamin D since I live in Seattle.

Hope this helps someone!


1 Luigi Fontana et al., “Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans”  PNAS, Vol. 101, no. 17, 2004.

2  Stephen D. Hursting et al., “Calorie Restruction, Aging, and Cancer Prevention: Mechanisms of Action and Applicability to Humans”, Annual Review of Medicine, Vol 54, 2003

3 Leonie K Heilbronn et al., “Calorie restriction and aging: review of the literature and implications for studies in humans”,  The American Journal of Clinical Nutrition, Col 78, No 3, 2003.

4  Timothy E. Meyes et al., “Long-Term Caloric Restriction Ameliorates the Decline in Diastolic Function in Humans”, Journal of the American College of Cardiology, Vol 47, Issue 2, 2005.

5  John O. Holloszy et al., “Caloric restriction in humans”, Experimental Gerontology, Vol 42, Issue 8, 2007

6  Leoine K. Heilbron et al., “Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals” JAMA, Vol 295, 2006

7 Thomas A. Wadden, “Treatment of Obesity by Moderate and Severe Caloric Restriction: Results of Clinical Research Trials”, Annals of Internal Medicing, Col. 199, No. 7, 1993

8 Amie J. Dirks et al., “Caloric restriction in humans: Potential pitfalls and health concerns”, Mechanisms of Ageing and Development, Vol. 127, Issue 1, 2006

9 Lipman et al., “Reduction in rate of occurrence of age related lesions in dietary restriction laboratory mice”, Growth Dev. Aging, 55, 1991

10 Roe et al., “The Biosure Study: influence of composition of diet and food consumption on longevity, degenerative diseases and neoplasia in Wistar rats studied for up to 30 months post weaning.” Food Chem. Toxicol. 33, 1995

11 Bellush et al., “Caloric restriction and spatial learning in old mice.” Physiol. Behav. 60, 1996

12 Means et al., “Mid-life onset of dietary restriction extends life and prolongs cognitive functioning.”, Physiol. Behav, Vol 54, 1993

13 Yu et al., “Nutritional influences on aging of Fischer 344 rats. Part I. Physical, metabolic, and longevity characteristics”, J. Gerontol. Vol 40, 1985

14 Heilbronn and Ravussin, “Calorie restriction and aging: review of the literature and implications for studies in humans” Am. J. Clin. Nutr, Vol 78, 2003

15 Fontana L, Partridge L, Longo VD. Extending healthy life span – from yeast to humans. Science. 2010;328:321–6.

16 Caloric restriction: powerful protection for the aging heart and vasculatureAm. J. Physiol. Heart Circ. Physiol. 1 October 2011: H1205-H1219.

17 Caloric restriction reduces growth of mammary tumors and metastasesCarcinogenesis 1 September 2011: 1381-1387.

18  Florez-Duquet and McDonald, 1998 M. Florez-Duquet and R.B. McDonald, Cold-induced thermoregulation and biological aging. Physiol. Rev.,  78  (1998), pp. 339–458.

19 Weindruch et al., 1986 R. Weindruch, R.L. Walford, S. Fligiel and D. Guthrie, The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr., 116  (1986), pp. 641–654.

20 Anson et al., 2003 R.M. Anson, Z. Guo, R. de Cabo, T. Iyun, M. Rios, A. Hagepanos, D.K. Ingram, M.A. Lane and M.P. Mattson, Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc. Natl. Acad. Sci. U.S.A.,  100  (2003), pp. 6216–6220.

21 Goodrick et al., 1990 C.L. Goodrick, D.K. Ingram, M.A. Reynolds, J.R. Freeman and N. Cider, Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age. Mech. Ageing Dev.,  55  (1990), pp. 69–87.

22 Dirks and Leeuwenburgh, 2004 A.J. Dirks and C. Leeuwenburgh, Aging and lifelong calorie restriction result in adaptations of skeletal muscle apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis, caspase-3, and caspase-12. Free Radic. Biol. Med.,  36  (2004), pp. 27–39.

23 Laurent Mouchiroud et al., “Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging”, BioFactors, 2010

24 Sirtris Announces Positive Results with Proprietary Version of Resveratrol, SRT501, in a Phase 1b Type 2 Diabetes Clinical Study, Business Wire, Jan 7, 2008

25 Anisimov, V. N., Berstein, L. M., Egormin, P. A., Piskunova, T. S., Popovich, I. G., Zabezhinski, M. A., Kovalenko, I. G., Poroshina, T. E., Semenchenko, A. V., Provinciali, M., et al. (2005). “Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice.” Exp Gerontol 40(8-9):685-693

26 Kaeberlein M., Burtner, C. R., Kennedy, B. K. (2007). Recent developments in yeast aging. Age Res Rev 6, 128-140