Calorie Restriction Mimetics

by | Jul 25, 2023 | Anti-aging, Articles, Conditions, Nutrition, Weight loss

Wouldn’t it be great to be able to improve your health, lose weight, and extend your maximum lifespan?  For over 80 years scientific studies have consistently shown that we can, as “calorie restriction” will do all these things!  It seems that by routinely reducing the amount of calories we consume by 40% or more this will defer disease and promote longevity.

Fortunately, over the last few decades research has shed light on compounds called “calorie restriction mimetics” (CRMs) that will help achieve the same amazing anti-aging benefits of calorie restriction.  Very few people have the willpower necessary to limit their food intake to the degree necessary to promote the regenerative anti-aging processes that are observed with calorie restriction, thus, one needs to employ a strategy of adding CRMs that will mimic the biological effects of calorie restriction.

CRMs include both pharmaceutical and natural compounds.  They work by various mechanisms, including influencing enzymes that control metabolism and protein synthesis, reducing the amount of damaged proteins and glycation end-products that “clog” up our cellular function, lowering inflammation and blood sugar, and improving insulin sensitivity.  Their profound effects on aging also include modulating the normal process of programmed cell death and influencing the genes that control cell repair and cell death.  In humans, this “anti-aging” gene is known as SIRT1.

SIRT1 codes for a protein called Sirtulin 1, and the effects of this protein family are just beginning to be understood.   Drug companies such as Sitris are working on Sirtulin 1 related compounds that may prove to be major players in the treatment of inflammation, diabetes, heart disease and dementia.  But we don’t have to wait as there are numerous CRMs available right now!

We can incorporate CRMs into our daily routine by including foods (avocado), herbs (gymnema, cinnamon), nutraceuticals (resveratrol, carnosine, alpha-lipoic acid, acetyl-L-cartinine) and even a few prescription drugs (metformin).

A Story of Wine and Longevity

Resveratrol is perhaps the most well known CRM.  Its discovery makes for a good story and good science…  Early researchers noted that calorie restriction caused the increased expression of certain “anti-aging” genes including SIRT1 in humans.  One theory was that nature must have provided a mechanism to increase our chance of survival during times of famine, and as such there might be similar genetic changes in the plant kingdom that are brought on by stress such as drought, and if we consume “stressed” plants then we might stimulate the anti-aging genes without having to restrict calories.

Harvard Medical School researcher David Sinclair, PhD will be forever linked to resveratrol.  He tested thousands of natural compounds in search of something that might increase expression of the SIRT1 gene.  The story goes, that a wine grower in Australia heard of Dr Sinclair’s research on “stressed” plants.  This wine grower was suffering from a bad investment in a diseased orchard that was infected with a fungus.  He called Dr Sinclair and offered to send him all the concentrated grape extract he would like.  The extract from these “stressed” grapes apparently led to the “eureka moment” as Dr Sinclair found the SIRT1 gene expression was significantly increased.  The specific compound was later found to be resveratrol.

Resveratrol compounds are found primarily in the skin of red grapes.  Some believe this may partly explain the “French paradox” in which the French people tend to live longer and have less heart disease than Americans despite more smoking and richer foods.  The regular consumption of red wine by the French may explain this paradox.

Wine and Weight Loss?!

In the most famous resveratrol study to date Dr Sinclair fed two groups of mice a high fat diet (60% of calories from fat) and fed a third group a standard healthy diet.  One of the groups being fed the high fat diet was also given resveratrol.  The mice given the high fat diet with no resveratrol suffered the typical problems normally associated with obesity – they were incredibly lethargic, started to develop diabetes, and died much earlier than the other two groups.  Meanwhile, the high fat plus resveratrol and standard diet groups had a 30% lower risk of death than the high fat group, did not gain weight, and greatly outperformed the high fat group in fitness tests.

Classes of molecules found in natural whole grape, grape skin, and grape seed extracts include potent effectors like proanthocyanidins (in grape seed), anthocyanins (which give purple and red grapes their color), and single molecular entities such as resveratrol and quercetin.  More recent studies confirm that SIRT1 gene expression benefits can be obtained by synthetic resveratrol or natural grape extracts.

The original studies in mice that confirmed the anti-aging and anti-obesity benefits were done with relatively large doses of resveratrol.  Given the concentration of resveratrol in the average glass of wine one would need to consume about 200 bottles to get the same amount of resveratrol.  That’s a lot of wine!

Resveratrol instead of Wine

Further studies done by BioMarker Pharmaceuticals confirm the anti-aging benefits of resveratrol but at doses roughly 10-fold less than the original studies.  This translates to a good human dose of at least 20mg daily, roughly equal to 40 glasses of wine.  Fortunately, resveratrol is readily available as an inexpensive supplement.  I recommend “trans-resveratrol” products from either Life Extension or Douglas Labs, in common doses from 25-200mg daily.

Please note that good health and longetivity are not simply the result of taking a few isolated supplements.  The different CRMs work in different ways and one should supplement with several of them to get a synergistic result.  Combining healthy lifestyle factors with targeted broad-spectrum supplements is the right combination.  Eat well at every meal, exercise regularly, sleep plenty, and manage stress – mix that with several CRMs and you have a recipe for a long and healthy life!

The Prolon “fasting mimicking diet”

Fasting will stimulate some of the same pathways as CRMs.  We recommend a 5 day fasting mimicking diet developed by anti-aging researcher Dr Valter Longo, called the Prolon diet.  Well researched and backed by decades of anti-aging science this simple 5 day program will turn on positive genetic and metabolic switches may lead to increased lifespan and better metabolism.  We often have patients do the Prolon diet before embarking on a specific program for weight loss.


Scott Rollins, MD, is Board Certified with the American Board of Family Practice and the American Board of Anti-Aging and Regenerative Medicine.  He specializes in bioidentical hormone replacement for men and women, thyroid and adrenal disorders, fibromyalgia and other complex medical conditions.  He is founder and medical director of the Integrative Medicine Center of Western Colorado ( and Bellezza Laser Aesthetics (   Call (970) 245-6911 for an appointment or more information.

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