CALORIC RESTRICTION AND LONGEVITY: HOW LESS EQUALS MORE OVER A LIFETIME

Caloric restriction has been recently touted as one of the biggest anti-aging secrets behind living for over 100 years. Reflective of the wisdom that ‘less is more’, the long-term benefits of consuming fewer calories appear to speak for themselves.

In this article, current knowledge on caloric restriction is discussed in the context of aging, health, and well-being. Its effects on metabolism are briefly discussed, followed by benefits, types, and safety, as well as tips on best practices for practicing caloric restriction.

What is Caloric Restriction?

Caloric restriction refers to the practice of lowering dietary energy intake below prior energy requirements in the absence of malnutrition. The goal of caloric restriction is to lower the resting metabolic rate. Over time, it begins to shift the metabolism to a lower energy state, meaning that less energy is needed to sustain body functions during rest.

Metabolic Rate: The Secret Behind the Benefits of Caloric Restriction

Metabolism, Rate of Living and Lifespan. According to the ‘rate of living’ theory, every organism has a finite metabolic potential – in other words, a limited amount of energy that can be produced and expended during its lifespan.^[1] The concept of caloric restriction came into being after observing that the rate at which the metabolic potential is expended (metabolic rate) is indirectly proportional to lifespan. Theoretically, the less energy the body expends to carry out its functions, the longer the lifespan of the organism. Resting metabolic rate (RMR) is used to assess the rate at which one’s metabolic potential is expended and is also a reflection of mitochondrial efficiency.

Uncoupling Metabolic Rate and Overall Energy Expenditure. The amount of energy consumed overall is not the same as the resting metabolic rate. Resting or basal metabolic rate is used to measure the efficiency of energy production at any given point. If the resting metabolic rate is higher on average, more energy is used to perform any cellular functions, including during physical activity, digestion, and storage of energy substrates (i.e., fat accumulation). An elevated resting metabolic rate appears to be closely coupled with increased physiological stress^[2] (and mitochondrial oxidative stress), which has little to do with increasing one’s energy output (activity levels)^[3]. A chronically high resting metabolic rate is a sign of mitochondrial inefficiency^[4], which typically lends itself to problematic energy production and utilization in the long run.

Oxidative Stress, Aging, and Metabolic Efficiency. The rate of living theory is connected to many other theories of aging pertaining to mitochondrial oxidative stress. 1-3% of the oxygen consumed to produce energy is believed to be converted into oxygen-free radical species that are capable of damaging cellular structures when not balanced with cellular antioxidants. The resting metabolic rate can increase the level of oxidation that occurs as well as the degree of free radicals produced as a result. Over time and with aging, more energy is expended, more damage to cells can accumulate, and regulatory antioxidant mechanisms become less functional. Healthy, aged individuals are known to have a lower resting metabolic rate, which is a possible compensation for diminished cellular functions after a lifetime of oxidative stress accumulation.^[5]

Disease and Metabolic Rate. Secondary aging as a result of disease or life stressors impacts cellular function in a similar way to that of ordinary aging. Initially, they serve to increase resting metabolic rate, oxidative stress levels, and free radical production. In the later (terminal) stages of the disease, the resting metabolic rate slows down and is comparable to that of advanced aging.^[6] This is usually related to mass reduction (i.e., muscle wasting and bone density loss).

Factors Influencing RMR. Resting metabolic rate can be increased by many factors, including:

• Elevated Protein Levels usually reflect an increase in the basal metabolic rate. Protein turnover is typically associated with an increase in oxidative stress, inflammation, cellular damage, and tissue recovery.
• Chronic Stress and other types of physiological stress raise the basal metabolic rate and are typically associated with inflammation.
• Genetics also play a role in affecting RMR due to coding various aspects of energy production capacity; such as the number of mitochondrial cytochrome c and cytochrome c oxidase enzymes, which correlate with metabolic rate. Organisms that live longer tend to have a lesser amount of these enzymes per cell (indicative of more efficient energy metabolism) than those with shorter lifespans.^[7]

Balanced Caloric Restriction Promotes Efficient Energy Production. Restricting calories lowers the supply of substrates for energy production, which eventually reduces the rate at which energy is produced and used at rest. A lower RMR in this context eventually promotes more efficient cellular energy production, which facilitates a better regulation of oxidative stress, lower free radical damage, and potentially, a slower aging process.

Reduced Calorie Intake Positively Redistributes Energy Expenditure. Caloric restriction promotes both a reduction in and a redistribution of energy expenditure. While overall energy requirements eventually reduce, less energy is also spent on digestion due to a lower intake of calories, which frees up more energy for physical activity.

12 Potential Health Benefits of Caloric Restriction

Caloric restriction has been studied in the context of historical food restriction, long-term trials, and animal studies, all of which have shown promising effects with respect to aging and metabolic health.

Potential benefits of restricting calorie intake include:

1. Longevity. Longevity is the primary benefit of caloric restriction seen across studies, with all other benefits contributing to it as the main outcome. In animal studies, caloric restriction increased lifespan anywhere between 50 and 300%. In humans ranging between 20 and 65 years of age, caloric restriction has been observed to add an extra 1-5 years onto the lifespan, with earlier adoption associated with greater longevity. Epidemiological studies reveal that in populations that inadvertently practiced caloric restriction, there existed a higher number of centenarians and a lower prevalence of mortality attributed to age-related diseases. During periods of war, food restrictions (without malnourishment) placed on various countries showed better mortality rates with 30-34% reductions.^[8]
2. Anti-Aging Effects. Caloric restriction has been observed to help lessen symptoms associated with aging by lowering the metabolic rate ahead of time. This has been shown to improve mitochondrial efficiency, lower oxygen, and energy requirements, reduce oxidative damage and slow the accumulation of aged (senescent) cells. It also encourages autophagy, a longevity-associated process whereby faulty cell components degrade and are renewed.^[9] In aging and many disease states, optimal autophagy is impaired. In a long-term trial of 2 years, results revealed that caloric restriction could slow down biological aging by an average of just over 84%, according to a standard biological age calculation. Participants in the study were aged 21-50 years and reduced caloric intake by roughly 12% on average.^[10]
3. Weight Loss. Most participants across studies that restricted their caloric intake experienced gradual weight loss. Weight loss was more for overweight participants and those who practiced caloric restriction for longer periods of time. When investigated further, weight loss across caloric restriction interventions has been shown to be largely related to fat mass reductions.
4. Increased Mitochondrial Availability and Function. Reducing the rate of metabolism appears to reduce oxidative stress, enhance mitochondrial function and promote improved mitochondrial turnover and repair. In subjects performing 25% caloric restriction for six months, the mitochondrial DNA content of muscle tissue increased by 35% by comparison to controls. This was accompanied by greater levels of mitochondrial gene expression that helped regulate cell function and lower cell DNA damage.^[11] While the activity of mitochondrial enzymes involved in energy production remained unchanged, the results imply that energy production overall is enhanced as more mitochondria are employed to produce energy at a slower, more controlled pace. Subsequent research has linked an increased level of functional mitochondria with elevations in ATP synthesis and utilization in the absence of excessive oxidative stress.
5. Caloric Restriction Benefits Are Long-Lasting and Promote Overall Biologic Efficiency. In a two-year caloric restriction study conducted on eight individuals, benefits were maintained while on a diet (38-58% caloric restriction). It sustained for up to 6 months after the trial period post resuming an ordinary Western diet. Benefits included reductions in many biomarkers for health, including weight, blood glucose and insulin, blood pressure, white blood cell count, total cholesterol, cortisol, thyroid hormone, and several other hormones such as renin and androstenedione. All changes were reflective of improved health, and participants were able to sustain higher levels of physical and mental activity during the trial period.^[12]
6. Improved Immune Function. In another two-year trial observing the effects of caloric restriction, participants were noted to have improved thymus function by the end of the trial. During the course of aging, the thymus gland is known to atrophy which lowers the production of T lymphocytes and overall adaptive immune competence. In response to the 25% restriction of calories, the thymic gland of participants had grown over the trial, exhibiting reductions in fat mass and an increase in lymphocyte production. This was attributed to the inhibition of a specific gene (PLA2G7), which is known to encode a platelet-activating factor and may be associated with thymic aging.^[13] Caloric restriction has also been associated with lowering white blood cell counts in healthy individuals^[14], which is consistent with reduced markers of inflammation and improved immune function. These results did not extend to active infections or the immune response to an allergy, revealing that restricting calorie intake does not seem to impair ordinary immune functioning. Some studies suggest that during an active infection, caloric restriction may reduce the immune response and is not advised^[15].
7. Reduced Inflammation. Mitochondrial oxidative stress serves as a signal for many cellular processes to occur. If excessive, it typically serves as a sign of cellular damage which signals the immune system to respond through increasing inflammation levels.^[16] A lack of chronic inflammation has been associated with heightened longevity, observed in centenarians aged between 100 and 110^[17]. Caloric restriction is associated with a wide-scale reduction in various inflammatory markers, including age-associated TNFa. However, results are inconsistent across studies, and it has been suggested that the degree of benefit depends on the age and inflammatory profile of the individual, as well as how long they have been restricting caloric intake.
8. Stem Cell Abundance. Experimental trials indicate that caloric restriction may have positive effects on regeneration by promoting more abundant stem cell reserves. This is believed to be mediated through preserved DNA integrity, as well as reduced sensitivity of stem cell reserves to wounds, resulting in a larger stem cell pool and a better regenerative response in the long run.^[18]
9. Enhanced Metabolic Health. Caloric restriction promotes less consumption of foods that would spike blood glucose levels and has naturally been associated with improved glycemic control. In longer studies over the course of 1-2 years, caloric restriction has been shown to lower insulin, blood glucose levels, and vascular inflammation, as well as enhance insulin sensitivity. In addition, long-term caloric restriction has proven to enhance the cholesterol profiles of individuals by lowering total cholesterol and triglycerides, and regulating the LDL : HDL ratio. Fat stores inside cells as well as in fatty tissue (including in the liver) were shown to decrease through the course of restricting calorie intake. It appears that fat-burning processes become more efficient inside the cell, likely as a result of increased mitochondrial availability and function. As a result, more fat is used to produce more energy during periods of fasting, yet less oxidative stress and inflammation occur as a result.
10. Cardio Improvements. Naturally, improvements in metabolic health lend themselves to better overall cardiovascular health. Over and above these benefits, caloric restriction has been shown to promote better function in the left ventricle of the heart after one year in healthy older adults. This benefit was noted to be similar to that of exercise. In a two-year trial, similar results could be seen in those aged 27-42 years, with enhanced left ventricular elasticity comparable to younger healthy adults. Additionally, the participants presented with a reduced risk for atherosclerotic cardiovascular disease, as reflected by a 40% reduction in lower carotid intima media thickness. Results from another study suggested that six months of caloric restriction may serve to lower the risk of contracting all-cause cardiovascular disease by up to 29% in 36 healthy volunteers.^[19]
11. Cognition. There are very few human studies that have taken a look at the cognitive effects of caloric restriction. However, it has been shown that caloric restriction is able to reduce the level of cortisol and other stress hormones, which would indirectly improve the amount of available BDNF (brain-derived neurotrophic factor) and may therefore be able to improve cognition in stressed or aged individuals. These results are mirrored in the majority of animal studies, whereby caloric restriction has been shown to lessen markers associated with age-related cognitive decline, including reductions in stress hormones and white matter loss, as well as memory and learning improvements.^{[20] [21]}
12. Disease Prevention Potential. Many states of disease have been linked to mitochondrial dysfunction over the last couple of decades. As caloric restriction can enhance mitochondrial viability and function, reduce low-grade oxidative stress and improve upon a wide range of metabolic markers, it may be a practical strategy for enhancing disease prevention. Human trials have predicted that caloric restriction can plausibly reduce the risk for obesity, cardiovascular disease^[22], atherosclerosis, hypertension^[23], non-alcoholic fatty liver disease, and type 2 diabetes^[24]. Preliminary research suggests that caloric restriction may be protective against neurodegenerative disorders and cognitive decline^[25].

Different Ways of Achieving Caloric Restriction

Caloric Restriction can be achieved in several different ways:

• Intermittent Fasting. Fasting is the practice of not eating at all for a limited period of time. In intermittent fasting, the participant decides to severely limit their food intake for structured periods of time, either for several hours of the day, alternating days in the week, or the month at large. This serves to reduce overall caloric intake throughout one’s lifespan and is known to yield similar benefits. However, caloric restriction may pose more stable benefits, depending on how consistently fasting occurs and for how long.^[26]
• Timing Meals for Optimal Metabolism. Time-restricted eating is a similar concept to that of intermittent fasting, yet it is often oriented towards aligning caloric intake with metabolic processes. Food consumed during the day contributes more to thermogenesis and daily activities than to the storage of energy substrates, whereas the opposite trend can be seen for food consumed in the late afternoon and evening.^[27] Eating during the day, therefore, contributes towards an improved energy balance, resulting in more efficient use of calories throughout the day and night.
• Conventional Calorie-Restricted Diet. This method demands working out the average amount of calories one consumes per day and then calculating caloric equivalents that promote reductions of between 10% and 40%. For this to work optimally, one needs to be consuming a diet high in nutrients. Caloric reductions can often be achieved by switching highly processed foods (high in calories) for highly nutritious foods (low in calories).

Which Method is Best?

There does not seem to be a caloric restriction method that poses more benefit over another method. Thus, the best method depends on the needs of the individual.

The Difference Appears Minimal Between Time-Restricted Eating and Caloric Restriction. In a small-scale trial on 139 participants, the differences between caloric restriction achieved either through dietary calorie control or time-restricted eating were minimal. Participants who limited consumption between 8 am and 4 pm lost 8kg on average over the course of a year, whereas those who limited their calorie intake lost 6.3kg on average in the same time period. All other health outcomes were similarly beneficial.^[28] It should be noted that restricting food intake to daylight hours has the added benefit of timing food intake with the metabolism and that if the time restriction was shifted into the evening, the results are likely to be completely different (as evidenced by the dietary outcomes of night shift workers). When the timing of food is accounted for, the differences in the above results are negligible.

Short-Term Fasting and Caloric Restriction Benefits Proved Similar. Fasting on alternate days (zero calories for 1-2 days; normal consumption every other day) proved to promote the same benefit as a continuous caloric restriction in young to middle-aged adults.^[29] However, alternate day fasting created a much greater negative energy balance (47% vs 28% on the caloric restriction diet), which implies a steeper utilization of stored energy reserves. Despite this difference, there was no compensation in eating habits once normal consumption resumed in alternate day fasting.

Intermittent Fasting or Time-Restricted Eating Can Be Easier to Implement. Despite these findings, precise caloric restriction is often more difficult to implement safely than time-restricted eating or intermittent fasting. Most people are not prepared to measure their nutrient intake or count their calories, and the process is prone to miscalculation.

Long-Term Consistency Promotes Better Metabolic Stability. While the results are comparable across studies for different types of caloric restriction diets, consistency is vital for reaping the long-term benefits. In trials that lowered metabolic rate, it has been observed that participants often compensated behaviorally by engaging in less physical activity. After 1-2 years, the metabolism eventually stabilized, and participants were engaging in their usual activity levels while consuming fewer calories. Intermittent fasting and time-restricted eating are prone to similar metabolic fluctuations that can affect physical activity levels until sufficient time has passed for the metabolism to fully adjust.

Is Caloric Restriction Safe? Side Effects and Contraindications

Caloric restriction is generally regarded as safe if carried out in the absence of malnutrition. Caloric restriction ought to be undertaken in the context of a nutrient-dense diet containing adequate protein, fats, carbs, and micronutrients to sustain health and well-being.

What is Caloric Over-Restriction? It is not certain at what point restricting calories would lead to starvation, provided the diet still contained adequate nutrition. Human studies have only truly looked at caloric restriction diets that limit between 10% and <40% of caloric intake, which have all shown considerable long-term benefits. Animal studies suggest that caloric restriction over 40% demands nutrient deprivation and gives rise to ill health effects.

Other Safety Considerations. Physical activity levels should also be considered with regard to caloric restriction, as well as current calorie intake. A healthy diet plan is often low in calories, and may not require a further restriction of calories. Furthermore, regular moderate-intensity exercise also contributes to reducing calories, improving one’s energy balance, and enhancing mitochondrial energy production. Individuals who engage in frequent physical activity and who consume a nutrient-dense diet likely already meet the baseline requirements of caloric restriction as a practice and are likely already receiving the benefit.

Side Effects. Without adequate nutrition, caloric restriction is not conducive to health and tends to promote starvation in the long run. Chronic over-restriction of calories and long-term starvation can result in the following side effects:

• Hypoglycemia
• Malnutrition and related symptoms
• Depression and anxiety
• Energy deficits
• Weakness and fatigue
• Lower bone mineral density
• Muscle wasting

Contraindications. Caloric restriction is not a recommended practice for any individuals with the following conditions:

• Health Conditions which Exhibit Any of the Above Symptoms. These include advanced diabetes, chronic fatigue, osteoporosis, diseases of malnourishment, etc.
• Pregnancy and Development. While there is a lack of human studies on caloric restriction in the context of pregnancy and development, animal trials suggest that it can limit the growth and development of offspring. This applied to offspring that were deprived of calories as well as to the offspring of mothers deprived during pregnancy.
• Elderly. Due to concerns pertaining to frailty, bone mineral density loss, and muscle wastage, the elderly are advised to avoid practicing conventional caloric restriction. By contrast, intermittent fasting or alternate-day fasting appears to benefit elderly individuals in trials.

How to Practice Caloric Restriction Safely

The concept of caloric restriction can be applied in any of the above ways (intermittent fasting, time-restricted eating, or calorie counting and reduction). The conventional approach demands counting calories and limiting their intake without compromising adequate nutrition.

Conventional caloric restriction begins with either using a calorie calculator, or visiting a dietician or a nutritionist that can help to define one’s current average caloric intake. This is based on age, height, weight, and physical activity levels. The average recommended caloric consumption for men is around 2500 per day and 2000 per day for women.^[30] Caloric restriction diets that show the best benefit typically opt for a 10-<40% reduction, which would equate to roughly 1550-2250 calories for men per day and 1250-1800 calories per day for women.

4 tips that may be useful when initiating conventional caloric restriction:

• Seeing a Healthcare Professional has the added advantage of having someone present to guide the process and who can ensure your diet does not fall behind in essential nutrition while attempting to lower caloric intake.
• Opting for a High-Fiber Whole Food Diet. A healthy balanced diet is still typically lower in calories than the average Western diet. Those consuming a diet high in processed foods can naturally lower their caloric intake by simply switching over to a nutrient-dense diet that emphasizes plant-based whole foods.
• Zero Calorie Beverages. Water and unsweetened drinks tend to contribute negligibly towards calories consumed during the day. When making beverages, calorie intake can be lessened by opting for water, tea, or pure coffee without sugar, sweetener, or milk.
• Reducing Portion Sizes is perhaps one of the most intuitive ways one can begin to restrict calories.
• Using Other Methods. Time-restricted eating or intermittent fasting could be easier approaches than calorie counting.

Antioxidant Phytochemicals Promote Caloric Restriction and Longevity

Non-essential plant-based nutrients have been found to be responsible for the health-promoting benefits of whole foods.^[31] Many of their antioxidant effects were also shown to be comparable to various components of caloric restriction.^[32]

They are present throughout the diet, mainly in fruits, vegetables, legumes, herbs, spices, whole grains, nuts, and seeds. All antioxidant phytochemicals are typically consumed in tiny amounts, averaging a few hundred micrograms to several milligrams per day. While their quantities are minimal (and even less in processed foods), their collective dietary presence and benefit have been shown through epidemiological studies linked with optimal health, longevity, inflammation control, and a reduced risk of acquiring disease.^[33]

In animal and other studies, most of these plant-based nutrients failed to extend lifespan in short-term trials alone. However, their effects appear to enhance the longevity-promotion effects of caloric restriction, making them complementary.^[34] Diets rich in these compounds are also typical of nutrient-dense caloric restriction diets, suggesting that they may be key to restricting energy intake.

The complementary benefits of some of the better-studied phytochemicals are highlighted below:

• Resveratrol is a well-studied polyphenol that has been shown to increase the effects of caloric restriction by reducing oxidative stress levels, and enhancing autophagy and cellular repair. In a small-scale study, high-dose resveratrol supplementation proved to increase biomarkers associated with longevity, enhance fat burning, improve energy production, and lower blood pressure in overweight individuals.^[35] Dietary sources include dark berries (grape skins, blueberries, bilberries, cranberries), cocoa, peanuts, and pistachios.
• Catechins and Epicatechins. Catechins and epicatechins were shown to reduce DNA damage, cellular oxidation, and inflammation across in vitro and in vivo studies.^[36] Green tea extract is perhaps the best-studied source of these nutrients, containing high levels of epigallocatechin gallate alongside many other types of catechins and epicatechins. Studies show that green tea extracts help promote weight loss through increasing thermogenesis, enhance blood glucose control and help lessen markers associated with cardiometabolic disease risk.^[37] Other dietary sources of catechins and epicatechins include fruits high in other antioxidants (e.g., stone fruits, berries, apples and pears), and other herbal teas.^[38]
• Hibiscus Tea. Preliminary trials show that hibiscus tea can gradually lower blood pressure markers in hypertense individuals^[39] and fat reserves^[40] in obese participants and those with fatty liver if regularly consumed over a period of 1-3 months or longer. Nutrients present in low quantities in hibiscus were found to inhibit cellular promoters of fat production and stimulate cell regenerative processes (autophagy).

Physical Activity as Complementary to Caloric Restriction

While it might seem counterintuitive, physical activity is a necessary component in balancing metabolism and promoting longevity. Physical activity appears to be one of the only factors capable of increasing energy expenditure, metabolic rate, and longevity. Caloric restriction in itself helps to reduce the energy expended during physical activity.

Inconsistent Caloric Restriction Can Lower Physical Activity Levels. It has been observed that after six months to a year of caloric restriction, physical activity levels decline, possibly as a form of compensation for reduced energy intake. However, after two years, this effect seems to normalize, and activity levels increase back to baseline. Therefore, caloric restriction should probably not be used as a short-term strategy for optimizing energy levels as it may promote reduced physical activity. In the long term, caloric restriction can enhance physical activity by increasing available ATP (energy) and lowering bodily energy requirements (via body mass reduction).^[41]

Exercise Consistency Better Enhances Caloric Restriction Benefit. A handful of studies show that the resting metabolic rate is slightly elevated after acute exercise due to changes in oxygen uptake. These effects do not appear to be carried forward with consistent, long-term exercise, wherein resting metabolic rate remains largely unaffected after engaging in physical activity.^[42] Other reviews mirror these results, revealing that regular exercise serves to negate the consequences of increasing free radical production^[43], which can be problematic in the context of acute or exhaustive exercise. ^[44]

Conclusion

While there is no ultimate cure for aging, it would seem that extending our mortality may be as simple as processing less on a daily basis. Restricting calories is able to lower the metabolic rate and significantly enhance energy production, with noticeable long-term benefits on health and the quality of aging. Unprocessed, plant-based whole foods and physical activity offer complementary benefits to that of caloric restriction through promoting optimal energy metabolism.

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