Fasting in Health and During Disease

Fasting in Health and During Disease

Summary

Voluntary fasting, whether intermittent or continuous, religious or therapeutic, is becoming increasingly popular. Despite the scarcity of randomized and controlled studies in humans, therapeutic fasting is often proposed in specific chronic pathologies, such as type 2 diabetes, high blood pressure, and cancer. It is also practiced to lose weight in overweight or obese subjects. Its practice is not without risks. 

 

Weight loss is often associated with a loss of lean body mass, which is a poor prognostic factor. 

 

Finally, while the caloric restriction is associated with longevity in some animal studies, its effects have been little studied in humans. Good quality clinical studies are needed better to evaluate the impact of fasting on health and disease.

 

Introduction

Fasting is a mode of deprivation of food and energy drinks, voluntary or involuntary. Physiologically, at the onset of fasting (seven hours after energy intake), the main metabolic characteristic is the obligation to supply glucose to tissues by hepatic glycogenolysis initially. 

 

When fasting is prolonged, glycogen stores are depleted, insulin levels drop, and fatty acids are released by lipolysis of triglycerides stored in fat tissue; these fatty acids will be used preferentially as energy substrates by specific tissues capable of metabolizing them (muscles, heart), while glucose will be "reserved" for other organs (brain, red blood cells). 


After depletion of glycogen reserves, glucose-dependent tissues will be supplied with glucose by gluconeogenesis from amino acids, mainly glycerol. 

 

During this period called "short fasting," the muscle thus becomes an essential producer of amino acids via increased muscle proteolysis. At the same time, muscle synthesis is reduced, resulting in rapid muscle wasting. A phase of adaptation to prolonged fasting occurs after 4-5 days with ketone bodies as energy substrates, particularly for the brain. Ketone bodies are metabolites produced by hepatic ketogenesis from fatty acids. The result is a decrease in gluconeogenesis and, therefore, a reduction in muscle protein hyper-catabolism. 

 

The mechanisms allowing this nitrogen saving are not fully elucidated. The practice of physical activity during fasting could make it possible to limit muscle wasting, and prayer/meditation could also have beneficial effects by inhibiting the axis of stress.

 

Voluntary Religious Fasting

Voluntary fasting is becoming increasingly popular in our food-abundant societies and is often aimed at correcting a continuous excess of caloric intake harmful to health. Voluntary fasting can be religious; food deprivation is then associated with spiritual enhancement. 

 

There are many types of religious fasting, intermittent or continuous, of varying durations (from 1 to 200 days per year), more or less restrictive, associated or not with physical activity, prayer, and meditation. 

 

In a recent literature search, the cardiometabolic effects of different types of religious fasts were evaluated. Although beneficial effects have been reported, including carbohydrate-lipid metabolism, inflammation, oxidative stress, most currently available studies are non-randomized, uncontrolled, and trim. Further studies are needed to understand better the mechanisms involved in the metabolic effects of religious fasting.

 

Therapeutic Fasting

Fasting is more and more considered as a healing path in many pathologies. Many claims are not supported by reliable scientific data or are based on animal studies. 


A distinction must be made between intermittent fasting (periodic caloric restriction) and continuous caloric restriction in these studies.

 

Fasting and Cardiovascular Risk Factors

Early epidemiological studies reported that the practice of intermittent fasting was associated with a lower prevalence of cardiovascular disease and diabetes in a Mormon population in Utah. 

 

More recently, in search of the literature, Horne and coll. Reported on the effects of intermittent fasting on cardiovascular risk factors in humans: weight, lipid profile, and type 2 diabetes. Only three randomized controlled studies reported beneficial effects of fasting, including decreases in body fat, LDL-cholesterol, triglycerides, and CRP. 

 

However, partly due to the lack of multivariate analyses and evaluation of the adverse effects of fasting, the low methodological quality does not allow for a conclusion. Further randomized controlled clinical studies are needed to assess better and understand the cardiovascular effects of fasting in humans.

 

Is it Necessary to Fast to Lose weight?

Caloric restriction (periodic or continuous) is often practiced to achieve weight loss in situations of overweight/obesity and also in cases of restrictive eating disorders. Nevertheless, few well-conducted randomized controlled studies evaluate the effects of this restriction on weight in the medium and long term. In the prospective randomized controlled study CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy), Marlatt et al. evaluated the impact of continuous caloric restriction (-12% of daily caloric intake) for two years in 39 non-obese subjects. 

 

At two years, the mean weight loss was nine ± 0.6 kg, associated with decreased body fat, improved lipid profile, and insulin sensitivity. Two years after the end of the study, about 50% of the subjects showed weight loss maintenance, probably reinforced by restrictive eating behavior.

 

Furthermore, in a meta-analysis published in 2018, Harris and coll. Reported significantly higher weight loss in obese subjects with intermittent fasting than a control group of obese subjects without therapeutic intervention (- 4.14 kg; 95% CI: - 6.30 kg to - 1.99 kg; p ≤ 0.001; 2 studies). In addition, no significant difference was observed in the effects of intermittent fasting and continuous caloric restriction on weight loss in obese subjects (- 1.03 kg; 95% CI: - 2.46 kg to 0.40 kg; p = 0.156; 4 studies). Decreases in body fat, abdominal circumference, and insulin levels were significantly greater during intermittent fasting than continuous caloric restriction. 

 

However, these results must be interpreted with caution given the small number of studies included, their low methodological quality (2 randomized studies; 10 men in the analysis), and their short evaluation period, on average five months (3 to 12 months). It should also be kept in mind that in these studies, weight loss is associated with a loss of fat mass, but also of lean body mass, a poor prognostic factor. 


Furthermore, the lower the bodyweight of the fasting subject initially, the greater the adverse effect of fasting on lean body mass and the greater the risk of fat expansion when fasting is stopped.

 

Metabolically, in a recent Geneva study by Mirko Trajkovski and coll. Mice subjected to daily caloric restriction (60% of usual caloric intake) showed browning of subcutaneous and visceral adipose tissue and decreased the volume of white adipose tissue and the size of adipocytes. 

 

Since browning fat plays a significant role in thermogenesis by increasing energy expenditure, some researchers would consider fasting, or more precisely continuous caloric restriction, as an attractive therapeutic avenue in the management of obesity. Further studies in humans are needed to understand better the mechanisms involved.

 

Fasting and Cancer

Intermittent fasting is believed to be beneficial in the prevention and treatment of cancer. Throughout life, free radicals' accumulation causes cellular dysfunction and DNA mutations that lead to aging and certain diseases, including cancer. 

 

Fasting is known to trigger cellular protective mechanisms, including cell cycle arrest and autophagy, which reduces free radical capital and recycles organelles, proteins, and other metabolites through autolysosomes. 

 

The molecular mechanism for activating autophagy during fasting is through inhibition of the insulin pathway (Ras, Akt, and mTOR), a path targeted by novel anti-cancer molecules. Experimental evidence suggests that fasting can be considered in prevention and adjunct to chemotherapy to improve therapeutic efficacy while protecting healthy tissues from excessive chemotoxicity. 

 

In healthy cells with functional cell cycle regulatory mechanisms, fasting would induce cell cycle arrest and autophagy, allowing the elimination of metabolites and free radicals produced by chemotherapy. 

 

In cancer cells, on the other hand, the presence of mutations, translocations, and oncogenic amplifications would prevent their passage into stress-resistant mode and promote the induction of apoptosis or necrosis following cellular damage caused by chemotherapy.

 

Although the scientific rationale for fasting in oncology is convincing, evidence of improved therapeutic efficacy is still awaited. The lack of usable clinical data may be explained by certain methodological constraints facing clinical studies on fasting, such as biased recruitment of participants already convinced of its effectiveness, the impossibility of a double-blind protocol, the heterogeneity of cancers and treatments, or even a holistic approach with multiple interventions (enema, physiotherapy or hydrotherapy). 

 

Besides, treating physicians may be reluctant to offer intermittent fasting to their patients for fear of compromising their nutritional status and promoting cancer cachexia. 

 

This last point is particularly relevant in light of the recent recommendations issued by the European Society for Clinical Nutrition and Metabolism (ESPEN) to combat the high rate of undernutrition observed in cancer patients. Experts from the French NACRe network (Réseau national alimentation cancer recherche) recommend proposing and implementing a dietary and nutritional evaluation before any glucidocaloric restriction diet. 

 

In case of undernutrition or significant risk of undernutrition, the practice of a glucidocaloric restriction diet is then not recommended. For this reason, intermittent fasting is only clinically evaluated in the treatment of cancers where weight loss is not a limiting factor. 

 

The close relationship between insulin, obesity, and breast cancer makes these patients particularly suitable candidates for this type of treatment strategy. Our experience has shown that a 54-year-old patient with grade 3 invasive ductal carcinoma (lymph nodes+, estrogen+, progesterone+, HER2+) can fully recover her fat and lean body mass between cycles of fasting adapted to the biological half-life of the chemotherapeutic agent (3 FEC [5-Fluorouracil, Epirubicin, Cyclophosphamide] + 3 Taxotere [docetaxel] + Herceptin [trastuzumab]). The patient did not experience any sensation of discomfort or cravings, despite blood glucose levels between 2.2 and 2.8 mmol/l during the fasting cycles. She tolerated moderate physical activity during fasting episodes better and was able to maintain 50% activity. 

 

The resumption of intestinal transit took place the day after the cessation of fasting. Our observations are similar to the results of published clinical studies.23 They show that fasting is well tolerated during chemotherapy and does not carry a risk of long-term weight loss. It appears to reduce asthenia, gastrointestinal problems, and hematological chemotoxicity. 

 

Patients report a positive effect on their sense of psychological and physical well-being. However, a better therapeutic efficacy has yet to be demonstrated.

 

Aging and Longevity

The effect of continuous caloric restriction on longevity has been studied in animal experiments, particularly in rodents. A 40% reduction in daily caloric intake increased their lifespan by 30-50%. 


Work published in Nature Communications reported that the beneficial effect of intermittent fasting on male C57/BL6 mice's longevity was to delay the onset of neoplastic processes, not to slow aging. Several metabolic mechanisms are believed to be involved. In humans, studies are rare and epidemiological. Centenarians on the Japanese island of Okinawa consumed 17% and 40% fewer calories daily than the average Japanese and American adult, respectively.

 

Conclusion

Due to the scarcity of studies in humans, it is challenging to establish recommendations in favor of therapeutic fasting in the context of chronic cardiovascular pathologies, diabetes, and obesity. Preliminary clinical results suggest that fasting decreases asthenia, gastrointestinal problems, and chemotoxicity for cancer. 

 

Patients report an improvement in their mental and physical well-being. However, it remains to be demonstrated that fasting has no detrimental effect on lean body mass and can potentiate chemotherapy.



References

BD Horne JB Muhlestein JL. Anderson Health effects of intermittent fasting: hormesis or harm? A systematic review. Am J Clin Nutr 2015

J *Most LA Gilmore SR Smith Significant improvement in cardiometabolic health in healthy non-obese individuals during caloric restriction-induced weight loss and weight loss maintenance. Am J Physiol Endocrinol Metab 2017

KL *Marlatt LM Redman JH Burton Persistence of weight loss and acquired behaviors two y after stopping a 2-y calorie restriction intervention. Am J Clin Nutr 2017

L Harris S Hamilton LB Azevedo Intermittent fasting interventions for the treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI Database System Rev Implement Rep 2018

M Headland PM Clifton S Carter Weight-loss outcomes: a systematic review and meta-analysis of intermittent energy restriction trials lasting a minimum of 6 months. Nutrients 2016

S **Fabbiano N Suárez-Zamorano D Rigo Caloric restriction leads to browning of white adipose tissue through type 2 immune signaling. Cell Metab 2016

CH * O'Flanagan LA Smith SB McDonell When less may be more: calorie restriction and response to cancer therapy. BMC Med 2017

R Buono VD. Longo Starvation, stress resistance, and cancer. Trends Endocrinol Metab 2018

J *Arends V Baracos H Bertz ESPEN expert group recommendations for action against cancer-related malnutrition. Clin Nutr 2017

NACRe, RNACRe. Jeûne, régimes restrictifs et cancer: revue systématique des données scientifiques et analyse socio-anthropologique sur la place du jeûne en France, 2017

K Xie F Neff A Markert every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice. Nat Commun 2017

J **Most V Tosti LM Redman Calorie restriction in humans: an update. Ageing Res Rev 2017

RD Angeliki Persinaki S Karras C. Pichard Unraveling the metabolic health benefits of fasting related to religious beliefs: a narrative review. Nutrition 2017

Wilson Fisk

Hello, My Name is Wilson Fisk. I am the man behind HelthyFit. I have a passion for helping people move better, eat smarter, and live the best version.

1 Comments

  1. HelthyFit is an informative website about food and health and the articles do not replace the recommendations or diagnosis made by a professional. Consult your doctor for any health problem.

    ReplyDelete
Previous Post Next Post