Intermittent Fasting and Caloric Restriction on Longevity and Disease
Humans tend to transform any diet into a weight loss diet. People do that with the ketogenic diet which I talked about in a previous post. Currently, one of the most popular diets is the intermittent fasting diet with emphasis on caloric restriction. Intermittent fasting is taken on by many with the intention of increasing satiety, timing nutrient intake with our circadian rhythm, and increasing energy and longevity.
The basic premise of intermittent fasting involves taking periodic breaks from eating (except water) to restrict caloric intake or feeding times. Intermittent fasting is an umbrella term that is not consistent in terminology. While studies define many of the fasting subtypes differently, I will focus on the definitions used by Dr. Valter Longo as he is an expert on this topic and is heavily cited in many of the intermittent fasting studies.
Your diet should be tailored to your lifestyle. This 6-week customized meal plan can be made for intermittent fasting or any other lifestyle you follow so you can get the results you want.
Forms of Intermittent Fasting
Time-restricted feeding (TRF): the most common approach is a 16:8 system every day of the week. The 16:8 consists of a 16-hour fasting window and an 8-hour feeding window. In a more rigorous approach, the feeding window can be shortened to 4 hours.1
Alternate day fasting (ADF): A 24-hour fasting period, alternated with a 24-hour feeding period at maintenance calories.2 The most common system is 5:2 where ADF is performed two days a week. The literature describes fasting periods as consumption of about 400–600 kcal/day.3
Periodic Fasting (PF): A very extreme method of fasting lasting 3 days or longer every 2 or more weeks.2
Caloric restriction (CR): daily caloric intake is reduced chronically by 20%-40% without malnutrition and meal frequency is maintained.2 Food can be consumed any time of the day.
Figure 1. Examples of some of the forms of the intermittent fasting diet. Copyright © 2020 Fit With Heba, All rights reserved.
Among all the forms of intermittent fasting, caloric restriction is the most studied so I will minimize this review to just that.
Caloric restriction must be performed without malnutrition so people must optimize their diets to ensure adequate nutritional intake. This encourages people to be more aware of their diets, so they are more likely to eat healthier foods. This is far healthier than the average western diet that is heavily based on refined carbohydrates and sugars. Research has shown that excess calories shorten lifespan and Americans consume more calories than any other population and many of the foods they consume have minimal or no nutritional value.4
Figure 2. Caloric restriction does not always lead to an increase in whole nutritious foods but it can encourage people to lead healthier lifestyles to minimize malnutrition. Copyright © 2020 Fit With Heba, All rights reserved.
While we do not fully understand the effects of caloric restriction on human health, recent studies are beginning to shed light on the benefits of the diet.
Caloric Restriction on Longevity and Disease
Aging is an inevitable biological process where cells accumulate dysfunctional proteins and damaged organelles. Autophagy is the body’s ability to degrade such proteins and organelles and has been shown to play a major role in maintaining cellular integrity and influencing lifespan and longevity.5,6 Autophagy dysfunction has been linked in the pathogenesis of several age-related neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease.7
Autophagy appears to decline naturally with age8 and increasing data show that exercise and the caloric restriction increase autophagy activity in humans which mediates their known effects on aging and longevity.9,10,11
Currently, there are therapeutic approaches to enhance autophagy including gene therapy and several FDA-approved drugs but these drugs come with unwanted side effects.12 Animal studies and clinical trials support the promise of caloric restriction as a healthspan- and lifespan-extending therapy.13,14,15 Caloric restriction has been shown to protect against a number of age‐related pathologies in humans including cancer, type 2 diabetes, cardiovascular disease, and neurodegenerative disease.16,17,15 ,7
Figure 3. TORC1 is known to reduce autophagy. Caloric restriction inhibits TORC1 which increases autophagy, leading to numerous health benefits. Copyright © 2020 Fit With Heba, All rights reserved.
The target of rapamycin complex 1 (TORC1), a central kinase involved in protein translation, reduces autophagy. TORC1 is activated by nutrient availability and is inhibited by nutrient deprivation.18 Inhibition of TORC1 reduces the production of proteins in cells which may begin to accumulate and wreak havoc in the cells. Exercise and caloric restriction results in the downregulation of TORC1 activity and upregulation of autophagy.
Even modest caloric restriction practices can promote health.19,20 In one study, six days of mild caloric restriction followed by 1 day of fasting (120 kcal), totaling to a weekly deficit of 30%, improved body composition, and cholesterol levels.20 Various fasting methods have shown improvements in symptoms of type 2 diabetes.22 Another study showed reducing energy intake to 750–1,100 kcal/ day for only five consecutive days/month for 3 months resulted in improvements in body composition, blood pressure, fasting glucose, and LDL-cholesterol.20
Caloric restriction is sustainable in obese and non-obese people and studies show no negative effects on quality of life. Caloric restriction is a very promising non-drug therapeutic which may aid in the control and prevention of numerous diseases and health complications.
- Johnstone A. Fasting for weight loss: An effective strategy or latest dieting trend. International Journal of Obesity. 2014.
- Longo VD, Mattson MP. Fasting: Molecular mechanisms and clinical applications. Cell Metab. 2014.
- Harvie M, Howell A. Potential benefits and harms of intermittent energy restriction and intermittent fasting amongst obese, overweight and normal weight subjects-A narrative review of human and animal evidence. Behav Sci (Basel). 2017.
- Fuhrman J. The Hidden Dangers of Fast and Processed Food*. Am J Lifestyle Med. 2018.
- Macian F, Cuervo AM. Autophagy and the immune function in aging. Curr Opin Immunol. 2014.
- Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011.
- Yang Y, Zhang L. The effects of caloric restriction and its mimetics in Alzheimer’s disease through autophagy pathways. Food Funct. 2020.
- Feng Y, He D, Yao Z, Klionsky DJ. The machinery of macroautophagy. Cell Res. 2014.
- Escobar KA, Cole NH, Mermier CM, VanDusseldorp TA. Autophagy and aging: Maintaining the proteome through exercise and caloric restriction. Aging Cell. 2019.
- Vainshtein A, Grumati P, Sandri M, Bonaldo P. Skeletal muscle, autophagy, and physical activity: The ménage à trois of metabolic regulation in health and disease. J Mol Med. 2014.
- Madeo F, Maiuri MC, Kroemer G, et al. Essential role for autophagy in life span extension Find the latest version : Essential role for autophagy in life span extension. 2015.
- Levine B, Packer M, Codogno P, Levine B, Packer M, Codogno P. Development of autophagy inducers in clinical medicine. 2015.
- Mattison JA, Colman RJ, Beasley TM, et al. Caloric restriction improves health and survival of rhesus monkeys. Nat Commun. 2017.
- Ingram DK, de Cabo R. Calorie restriction in rodents: Caveats to consider. Ageing Res Rev. 2017.
- Most J, Tosti V, Redman LM, et al. Calorie restriction in humans: an update. Ageing Res Rev. 2017.
- Fontana L, Klein S. Aging, adiposity, and calorie restriction. J Am Med Assoc. 2007.
- Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A. 2004.
- Chang Hwa Jung, Seung-Hyun Ro, Jing Cao, Neil Michael Otto, Do-Hyung Kim. mTOR regulation and autophagy. FEBS Letters. 2011.
- MA Gillentine, LN Berry, RP Goin-Kochel, MA Ali, J Ge, D Guffey, JA Rosenfeld, V Hannig, P Bader, M Proud, M Shinawi, BH Graham1, A Lin, SR Lalani, J Reynolds, M Chen, T Grebe, CG Minard, P Stankiewicz, AL Beaudet and C, Schaaf. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance and healthspan. J Autism Dev Disord. 2017.
- Wei M, Brandhorst S, Shelehchi M, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017.
- Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF, Tangney CC, Varady KA. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations. Nutr Metab. 2012.
- Barnosky AR, Hoddy KK, Unterman TG, Varady KA. Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: A review of human findings. Transl Res. 2014.