The Calorie Restriction Diet: 1200 Calorie Diet on Longevity and Health
Calorie restriction can stimulate catabolic pathways, some of which are associated with metabolic improvements and longevity. By activating AMPK, FOXO, and Sirtuin-1, calorie restriction not only facilitates weight loss but can also acutely enhance cellular repair through processes like autophagy, potentially slowing aging.
What is Calorie Restriction
Calorie restriction (CR) is a dieting approach that emphasizes moderate (~10-20%) or severe (~30-40%) calorie reduction. The specific deficits depend on individual needs, baseline caloric requirement, and metabolic rate. For instance, a person with a maintenance calorie need of 2,500 kcal/day may practice moderate CR by consuming 2,250 kcal/day.
It is defined by a calorie deficit sufficiently low to achieve or maintain normal bodyweight without causing malnutrition. (1)
The reduction in total calories doesn’t undermine the importance of providing the essential nutrients the body needs to avoid catabolic dominance. This prevents the negative effects of malnourishment like bone, brain, and muscle degradation. As total calories are reduced, the importance of eating nutrient-dense foods to provide essential nutrients is amplified.
Research shows calorie restriction to be one of the most effective non-pharmaceutical strategies to lengthen lifespan.
Calorie Restriction, Longevity, and Sirtuins
In the quest for longevity, calorie restriction stands out as one of the major strategies. Generally, overeating leads to high insulin states which contribute to weight gain, metabolic dysfunction, and increased inflammation. This further amplifies with increased consumption of refined carbohydrates.
Certain methods like fasting, keto, or calorie restriction allow the body to tap into fats for fuel. This activates numerous catabolic pathways which enhance cellular repair and improve the way the body derives energy.
People in Okinawa eating 15% and 40% less calories (1785 kcal/day on average) than mainland Japanese and US population, respectively, had significantly more centenarians (50 per 100,000 people) and lower rates of cardiovascular disease and cancer. (1)
Data showcases CR to significantly improve metabolic markers like fasting glucose, insulin sensitivity, and lipid profile which are important in guarding from cardiometabolic risk factors. Additionally, CR aids in fat loss, weight loss, and reduction in waist circumference, particularly important for obese people. (2) (3) (4)
During lower caloric intake, the body activates catabolic pathways like AMPK, FOXO, and Sirtuin-1 which are correlated with longevity.
During CR or fasting, autophagy is stimulated, which enhances cellular repair, replacing dysfunctional with new, functional cells. This improves metabolic efficiency, reduces inflammation, and creates a healthier bodily environment. (5) (6) (7) (8)
Moderate CR in humans has also been shown to potentiate certain antiaging mechanisms, such as (9)
- neuroendocrine adaptations: improving insulin sensitivity and reducing anabolic hormones like testosterone and insulin
- reduced levels of thermoregulatory hormones (norepinephrine) and cellular metabolism (T3); *significant as lower body temperature is associated with longevity
- increased levels of anti-inflammatory hormones (cortisol, ghrelin)
Sirtuin-1 activation is another potent mechanism stimulated by CR that may affect longevity. SIRT-1 is an enzyme involved in deacetylation. Essentially, it alters proteins in a way that’s mostly favorable to longevity, so-called the the longevity gene. It targets DNA repair and stability, stress resistance, mitochondria function, and cell cycle progression (10) (11)
The majority of the data, both in humans and animal models, shows fasting and calorie restriction to be effective ways to stimulate catabolic pathways related to longevity, such as AMPK, FOXO, autophagy, and SIRT-1.
Potential Benefits of Calorie Restriction
Beyond the potential to increase lifespan, calorie restriction can significantly contribute to greater metabolic function, aid in weight loss, and protect the brain.
Weight Loss
Calorie expenditure is the primary determinant of weight loss. Expending more calories than consumed will lead to weight loss. Over time, reduced caloric intake also reduces metabolic rate, meaning the body gets used to functioning on, and burning fewer calories to maintain homeostasis.
Caloric restriction, with or without fasting, proves to be an effective approach to weight loss and fat loss. (12) (13) (3) Some data shows fasting’s superiority over calorie restriction, particularly in nonobese or T2D people, as it relates to reducing waist circumference, central fat distribution, and cardiometabolic risk. (14)
In some instances, combining a low-carbohydrate approach to calorie restriction may further amplify the benefits related to weight loss and fat loss. (2)
Partially, improvements in hormonal signaling and increasing gut microbiota diversity are linked to sustainable weight management after fasting or CR. This tackles the problem of fatigue and hunger people who tend to overrely on carbohydrates have. (15) (16) (5)
The drop in metabolic rate in calorie restriction occurs due to less energy being needed to sustain a smaller body and the body becoming more energy efficient by using fats for fuel. Most link slower metabolism to impaired fat loss, but CR seems to show the contrary.
BMR reduction is typically not as large to negate the calorie deficit, leading to better body composition and weight management even at a slower metabolic rate. The drop in metabolic rate is proportional to body weight reduction which instead of preventing fat loss, slows it down over time.
Metabolic Health
Eating fewer calories potentiates the reduction in consuming refined carbohydrates. The body is therefore alleviated of anabolic, high-insulin states and can shift to ketosis. This shift makes the utilization of glucose and fats favorable in increasing energy levels and enhancing metabolic health.
The digestion of glucose requires insulin to be secreted to transport that glucose to tissues, as energy stores. Consistent elevation in insulin which happens due to caloric surplus, particularly simple carbohydrates, increases the risk of weight gain, poor glucose control, and inflammation, the drivers of metabolic syndrome.
A large amount of data including RCTs, meta-analysis, and systematic reviews shows a strong link between reducing calorie or carbohydrates intake and improvements in metabolic function. CR and IF have been shown to improve (17) (13) (18) (8) (19)
- insulin sensitivity
- fasting glucose levels
- glycemic control (stability)
- HbA1c levels
- Lipid profile (Cholesterol, TG, LDL, and HDL levels)
- inflammatory markers
- utilization of ketones
- HOMA-IR
This metabolic shift produces significant fat loss which alleviates most of the risk factors for metabolic dysfunction that lead to weight gain, diabetes, and low energy.
Both fasting and calorie restriction have shown the potential to aid in fat loss, weight loss, improved hunger hormone signaling, and easier weight management. (3) (20) (21) (22)
Inflammation
Inflammation is a natural stimulus for recovery. As a by-product of functioning, the body produces inflammation. Low levels are essential for adaptation, while chronically elevated levels pose a risk to health. By modulating gut microbiota composition, fasting may lower inflammation. (14)
Calorie restriction in humans is known to aid in metabolic health and increase lifespan, partly depending on four mechanisms. One of these four is increased levels of hormones like cortisol, adiponectin, and ghrelin – which can suppress inflammation. (9)
Stimulating catabolic activity related to anti-aging pathways, such as AMPK and SIRT-1 is also proven to reduce inflammation and improve resistance to stress. (10)
CR may exert active actions on the hormonal, metabolic, and gene expression products that help alleviate inflammation in numerous tissues such as the liver, heart, muscle, fat tissue, neural tissue, and others. (23)
Neuroprotection
The energy metabolism in the brain determines its function over time. Increased reliance on carbohydrates provides short-term benefits, as the brain uses glucose. Long-term, this may lead to disruptions in glucose sensitivity in the brain, which contributes to cognitive decline.
Reduction in calories, just as with fasting, works by partly stimulating ketosis and/or neural autophagy. During ketosis, the brain becomes more efficient at utilizing fuels like ketones to power its cognitive tasks. This in turn improves insulin sensitivity too. Neural autophagy contributes to the clearance of misfolded proteins and dysfunctional cells, to repair them with new ones.
Generally, fasting or CR doesn’t provide strong acute benefits in healthy people. However, due to its mechanisms which aid in brain repair and more efficient use of fats, it can alter inflammation and mediate some of the damage the brain sustains. This helps sustain a functioning brain for longer, acting neuroprotective and potentially slowing down the progression of neurodegeneration. (24) (25) (26) (15) (27)
Certain mechanisms discussed in the literature regarding how calorie restriction may improve brain function and longevity include:
- reduction in inflammation and oxidative damage
- improvement in insulin sensitivity and use of ketones
- increase in BDNF or brain-derived neurotrophic factor
- activation of neural autophagy aiding in brain repair
- prevention of plaque accumulation
- reduction in neurotoxicity i.e., glutamate reduction
Taken together, the data showcases the potential of calorie restriction as a tool to ward off neurodegenerative diseases and slow down cognitive decline. By improving brain’s energy metabolism, ameliorating oxidative damage and neurotoxicity, and mediating neurotrophic factors, environment is improved, providing a larger bandwidth to support its function.
Mitochondria Function
One of the main mechanisms behind calorie restriction and extending lifespan lies in optimizing mitochondria function. The power cells that produce energy, fight oxidative damage, and aid longevity.
CR has been shown to increase sirtuin expression which supports mitochondria function. (10)
Whether calorie restriction impacts mitochondria biogenesis, which is the creation of new mitochondria, isn’t yet clear. One perspective shows an increased activation of AMPK, SIRT1 which stimulate PGC-1α, a key regulator of mitochondrial biogenesis.
In healthy humans, CR effectively increased the expression of proteins involved in mitochondrial function and creation in the muscle. (28) However, animal studies oppose this. Calorie restriction was shown ineffective in significantly upregulating the creation of new mitochondria. (29) (30) However, calorie restriction seems to benefit the mitochondria in different ways, and preserving their function via modulating mitochondrial respiration is an important one. (31) One is improving their efficiency in energy creation. By reducing oxidative stress and supporting the electron transport chain (ETC) function, it can aid in an increase in energy.
CR can stimulate mitophagy, which is like autophagy for the mitochondria. (32) It helps remove dysfunctional mitochondria to swap them for new functional ones. By triggering a mild stress, known as hormesis or mithormesis in mitochondria’s case, CR may strengthen mitochondrial resilience to environmental and metabolic stressors.
Intermittent Fasting vs Calorie Restriction
The one thing keto, fasting, and calorie restriction have in common is reducing the total amount of carbohydrates ingested. By manipulating timing, total intake, or fasting window, these approaches mainly work by stimulating a catabolic shift to ketosis where the body seems to improve metabolic function, repair faster, and ramp up energy production.
However, there are some key differences between fasting and calorie restriction.
Calorie Restriction
Calorie restriction is a continuous energy deficit. It can stimulate ketosis or not, but it will show a tendency for a lower carbohydrate intake. This leads to a gradual shift to fat oxidation which happens when one burns fat for fuel. It results in weight loss, reduction in metabolic rate, and moderate improvement in metabolic function.
Intermittent Fasting
Fasting on the other hand works by increasing the fasting window. During a fasted state, the body is presented with an energy deprivation challenge. It works hard to sustain energy, shifting to fat metabolism. Such glucose starvation decreases insulin and gives the body the break it needs from metabolizing glucose. It activates numerous catabolic pathways that ramp up cellular repair and fat burning.
Depending on the intensity, timing, and total caloric intake, both will have unique effects. But generally, both strategies are used to extend lifespan, but fasting has the edge due to its autophagy-stimulating properties. Other benefits include fat burning, increased energy, improved metabolic health, and brain function.
Fasting is a more dynamic, pulsed way of achieving this. It can have a more robust action, emphasizing a stronger shift in metabolism. CR on the other hand can be very light, continuous, and steady. A gradual energy deficit that doesn’t shock the body.
