Caloric Restriction
A Brief (and Promising) History
Memory Lane
Throughout history, humans have sought the proverbial Fountain of Youth. The quest for human longevity, both captivating and elusive, has been approached from various angles. A modern approach, which has been both venerated and contested, is caloric restriction (CR).
Simply put, CR refers to reducing caloric intake without increasing malnutrition. The notion of CR as a potential path to longevity stems back to ancient civilizations. You might’ve heard of the practice of fasting as an intervention.
Fasting, a form of extreme caloric restriction, has roots in spiritual and religious practices, often touted for its purifying effects on the soul and body.
However, it was only in the 20th century, particularly in rodent studies, that CR's potential benefits for life extension became a scientific curiosity. Initial experiments demonstrated that rats on a restricted diet lived significantly longer than those fed ad libitum.
Today, scientists are studying the effects of CR as a tool for weight loss in humans, though CR as a falsified method for life extension in humans and primates remains unclear.
Challenges in Clinical and Observational Data
Over the years, the fervor surrounding CR as a life-extending strategy grew, bolstered by some results in animal studies.
Worms, flies, and even mice exhibited longer lifespans under restricted diets. Further, these animals not only lived longer but also showcased delays in age-associated diseases.
Pretty neat.
However, while “there are many reports of lifespan and healthspan extension from CR, there are also multiple published examples where CR failed to extend lifespan. Among these are studies of wild-derived mice and studies of genetically inbred mouse strains.”
And “of the two long-term studies in rhesus monkeys, one reported a substantial increase in lifespan, while the other failed to detect any significant change,” according to one peer-reviewed study.
Translating these findings to humans presents challenges.
Observational studies, such as those examining populations with naturally lower caloric intakes or periods of famine, produce mixed results. Some studies suggest increased lifespan, while others indicate no significant difference or even potential harm.
Clinical trials like the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) investigated CR's effects in humans. Preliminary results indicated potential cardiovascular and metabolic benefits, hinting at improved healthspan.
The question of whether CR can significantly extend human lifespan beyond a few years remains unanswered due to the lengthy and complex nature of such trials.
A popular algorithm developed by epidemiologists called DunedinPACE, has become a gold standard of DNA methylation tests designed to measure aging.
“Dunedin,” after Dunedin Birth Cohort used to develop it, and PACE meaning Pace of Aging Computed from the Epigenome, “found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small.”
Both the clinical and observational are confirming and confounding.
CR Myth-Making
Culturally, the allure of CR has led to both admiration and skepticism. On one hand, societies influenced by Eastern philosophies embrace fasting and restricted diets as both spiritual and health practices.
The rise of intermittent fasting, detox diets, and other trends, can be traced back to CR principles and the history of fasting. But these interventions, what one scientist referred to me as “CR mimetic,” don’t quite mimic the same effects.
According to the study I mentioned earlier conducted by Mitchell B. Lee, Cristal M. Hill, Alessandro Bitto, and Matt Kaeberlein, entitled “Anti-aging: Separating fact from fiction,” the authors note how many of interventions design to mimic CR have generated more questions than answers outside of a laboratory setting.
The study notes “The renowned CR researcher Roy Walford attempted to popularize CR in the 1980s with his book “The 120 Year Diet: How to Double Your Vital Years”. Walford’s “CR Society” never grew beyond a small group of followers, likely because of the severe abstinence required to maintain a CR lifestyle, and Walford himself died at the age of 79, well short of the 120 years promised in the book title.
“Recently, however, several less stringent variations on CR have achieved greater popularity, including IF, TRF, PR, and KDs.”
Myths about CR have also proliferated across the fitness community.
Some view it as a paved path to longevity, while some researchers fear potential nutrient deficiencies, loss of muscle mass, or metabolic slowdown, over some extended period. For researchers, “separating fact from fiction” is crucial to science progress and public health.
In the context of CR, “less is always better” can be dangerous when extrapolated without caution and scientific support. For instance, CR without adequate protein intake can lead to unwanted muscle loss.
Muscle is considered a leading indicator of stability and longevity in older age, since sarcopenia (muscle loss) is inevitable. This is especially true in women as they age.
Comparison to Modern-Day Interventions
The potential benefits of CR have naturally spurred interest in finding other interventions that might mimic its effects, without necessitating stringent dieting.
Drugs like metformin, rapamycin, and resveratrol, are currently under investigation for their potential lifespan-extending properties. The underlying idea is to activate the same biological pathways that CR does, notably those related to cellular energy regulation, without having to cut down on calories.
Still, these drugs have multiple targets, were discovered by chance, and are not pure “CR-mimetics.” However, there’s promise.
For instance, rapamycin, an mTOR inhibitor, has demonstrated promise in extending lifespan in mice, resonating with the effects observed in CR experiments. Resveratrol, often associated with red wine, is also being examined for its potential to activate sirtuins, proteins linked to longevity.
Currently, all lack the known effects of CR.
Final Thoughts
While caloric restriction's history is rich and rooted in both science and culture, it remains a method with both ardent proponents and skeptics. Scientifically, while CR's benefits still being studied, its translation to human longevity is still a topic of debate.
As a weight loss tool, the so-called energy balance model (“calories in calories out”), is observed by exercise scientists as the gold standard for fat loss.
As a consumer of this approach, I admit that by maintaining a high satiety diet under a long-term (one year) calorie deficit, I was able to shed fat without compromising nutrition. Coupled with resistance training, I was able to build muscle at the same time.
My personal regimen to fat loss has been five-fold: consistent (3x a week) HIIT (high intensity interval training), TRF (time restricted feeding), CR (a diet of low-calorie foods), no snacking, and no ultra-processed foods.
I consume a whey protein isolate, and duck rillettes, which I put in my eggs, which are both technically processed. So I distinguish “process” from “ultra-processed” foods. I don’t eat fast food, for instance.
These interventions helped me lose fat during covid and have improved my blood biomarkers, including a resting heart rate of 45 (today it’s 47 ;)
With modern medicine's evolution, however, drugs seeking to mimic CR's effects also offer promising alternatives. I’ve yet to sample them, but I’m optimistic. There’s lots of progress in the space. In the meantime, like CR itself, new drugs require thorough investigation before being advocated for human longevity.
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