Fasting


Article Author:
Jarett Casale


Article Editor:
Steve Bhimji


Editors In Chief:
Divyesh Nemakayala
William Gossman


Managing Editors:
Frank Smeeks
Scott Dulebohn
Erin Hughes
Pritesh Sheth
Mark Pellegrini
James Hughes
Richard Ciresi
Phillip Hynes


Updated:
12/2/2018 12:28:32 PM

Introduction

Fasting is a practice that involves restriction of food or drink intake for any period. Fasting is practiced for a wide variety of reasons ranging from religious beliefs to medical testing. It is often used in medical practice for baseline laboratory tests of blood glucose and lipid markers to aid in the diagnosis of various diseases as well as quantifying risk factors. Various forms of therapeutic fasting have been studied regarding their ability to improve physiological indicators of health including insulin sensitivity, blood pressure, atherogenic lipids, inflammation, and body fat. Many of these studies In Islamic tradition, fasting during the month of Ramadan involves abstinence from food and drink each day from dawn until sunset. This results in a variety of metabolic and physiological adaptations that have been well studied. From a general perspective, this includes a change in metabolic energy sources from glucose in glycogen to triglyceride and protein catabolism.[1][1]

Issues of Concern

The effects of fasting have been well studied in healthy populations. However, data regarding regimens in pediatric, geriatric, and underweight patients is lacking. One of the most prominent effects noted in the beginning periods of fasting includes a tension-type headache. The etiology of these headaches are multifactorial and the exact causative factor has yet to be identified. Proposed mechanisms contributing to fasting headache include hypoglycemia, dehydration, and caffeine withdrawal. Studies have shown that use of a COX2 inhibitor, such as rofecoxib, is effective in preventing and attenuating fasting headache, suggesting that the etiology may be a product of the proinflammatory eicosanoid metabolic pathway. Fasting should always be performed under the supervision of a physician and when possible, done in a clinical setting.[6][2][3][4]

Cellular

Fasting involves a drastic change in cellular metabolism and physiology that occurs secondary to changes in energy sources that occur during the fasting process. Blood glucose is normally maintained in a relatively narrow window that provides the body with sufficient energy through the cellular process of glycolysis. During fasting, maintenance of blood glucose is provided by changes in metabolism that include an initial reliance on glycogen stores in the liver and skeletal muscle. Glycogen consists of chains of polymerized glucose monosaccharides that can be used for energy by the process of glycogenolysis. The vast majority of glycogen is stored in the liver, which plays the greatest role in maintaining blood glucose over the first 24 hours of fasting. After about 24 hours of fasting, glycogen stores become depleted which causes the body to utilize adipose tissue and protein stores for energy. The conversion from glycogen to alternative energy sources and resulting disturbance in blood glucose maintenance has been proposed as a cause of a headache noted during sundown in Muslims fasting for Ramadan. The change in metabolism following glycogen depletion is largely dependent on the metabolism of triglyceride stores in adipose tissue that are broken down into free fatty acids and glycerol and subsequently converted to ketone bodies and glucose, respectively, in the liver. These changes in cellular metabolism are facilitated by the hormones glucagon, epinephrine, and cortisol that all become elevated in times of fasting. Ketone bodies made from free fatty acids through the process of ketosis and include acetoacetate, beta-hydroxybutyrate, and acetone. These ketone bodies are then converted to acetyl-CoA and used for energy by the heart, brain, and skeletal muscle. The maintenance of these organs during times of starvation is crucial to survival by allowing maintenance of cognition and energy for hunting or gathering food. In addition to adipose catabolism, protein catabolism through the process of gluconeogenesis simultaneously takes place in times of fasting. Gluconeogenesis produces glucose from amino acids broken down from various tissues including muscle. After glycogen depletion, the reliance of body tissues on glucose for energy gradually declines in favor of ketone bodies, which become more readily available.[5][6][7][8][9]

Development

Fasting has also been studied regarding its ability to improve physiological markers of health. One of the most heavily studied fasting regimens is known as intermittent fasting, which involves restriction of caloric intake during a set period on a continual basis. Examples of fasting regimens include restriction of calories for 1 full day out of the week or 2 nonconsecutive days, known as the "5:2" diet. Animal studies have repeatedly demonstrated a vigorous, positive response of various health indicators to intermittent fasting regimens. These include improved insulin sensitivity and reduced body fat, atherogenic lipids, blood pressure, and IGF-1. Animal models have also demonstrated a statistically significant improvement in the ability of intermittent fasting to delay the progression of neurological diseases including Alzheimer’s, Parkinson’s, and Huntington’s disease. Human studies of intermittent fasting also demonstrate promising results in protection against metabolic syndrome and other lifestyle diseases including diabetes and cardiovascular disease. Current data suggest that larger clinical trials are warranted to further investigate the efficacy of prescribed fasting regimens for the treatment of chronic lifestyle and obesity-related diseases. A notable cellular process that is upregulated in times of fasting involves the inhibition of the enzyme tyrosine kinase. Inhibition of this enzyme is a mainstay of treatment for many types of cancer, and further research is necessary to evaluate whether fasting regimens can be used concomitantly with chemotherapy to improve patient outcomes.[10][1][11][5][6]

Related Testing

Fasting has also been studied regarding its ability to improve physiological markers of health. One of the most heavily studied fasting regimens is known as intermittent fasting, which involves restriction of caloric intake during a set period on a continual basis. Examples of fasting regimens include restriction of calories for 1 full day out of the week or 2 nonconsecutive days, known as the "5:2" diet. Animal studies have repeatedly demonstrated a vigorous, positive response of various health indicators to intermittent fasting regimens. These include improved insulin sensitivity and reduced body fat, atherogenic lipids, blood pressure, and IGF-1. Animal models have also demonstrated a statistically significant improvement in the ability of intermittent fasting to delay the progression of neurological diseases including Alzheimer’s, Parkinson’s, and Huntington’s disease. Human studies of intermittent fasting also demonstrate promising results in protection against metabolic syndrome and other lifestyle diseases including diabetes and cardiovascular disease. Current data suggest that larger clinical trials are warranted to further investigate the efficacy of prescribed fasting regimens for the treatment of chronic lifestyle and obesity-related diseases. A notable cellular process that is upregulated in times of fasting involves the inhibition of the enzyme tyrosine kinase. Inhibition of this enzyme is a mainstay of treatment for many types of cancer, and further research is necessary to evaluate whether fasting regimens can be used concomitantly with chemotherapy to improve patient outcomes.[10][1][11][5][6]

Clinical Significance

Fasting is performed clinically when blood tests require minimal caloric intake to aid in the diagnosis of various diseases. Fasting blood glucose is an example of a test that helps to aid in the diagnosis of diabetes mellitus based on a set threshold that determines if a patient’s insulin receptors are functioning properly by their ability to lower blood glucose in response to insulin. In cases of diabetes mellitus type 2, insulin resistance results in high fasting blood glucose. Additionally, high fasting blood glucose has been studied as a risk factor for the development of high blood pressure.

Another test that traditionally requires a patient to be fasting for accuracy includes triglyceride measurement on a lipid panel. Blood triglycerides are present in substantial quantity in the carrier proteins chylomicrons and very low-density lipoprotein (VLDL). Chylomicrons are responsible for carrying triglycerides from digested food to peripheral tissues while VLDL is made in the liver and represents a baseline blood triglyceride level resilient to food intake. Therefore, an accurate measurement of blood triglycerides in VLDL require a patient to be fasting to exclude chylomicron triglycerides from the measurement. Recent data suggest that accurate lipid measurement may be possible in the absence of fasting although fasting for lipid panels is still currently the standard of care.[12][13][14]


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Fasting - Questions

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A patient has been fasting for several days and his glucose level is 60% of his normal level. The patient is asymptomatic. His brain is primarily using what alternative energy source?



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Which holiday can often causes headache by sundown?



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A healthy male is fasting for religious reasons. After 16 hours without food or water, his blood glucose level remains in the normal range. Which of the following organs played the greatest role in maintaining his blood glucose?



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Hunger pangs:



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Which of the following is not a ketone body made from free fatty acids in the liver during periods of fasting?



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Which of the following interventions has been shown to be effective in preventing and attenuating fasting headache?



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Why is fasting important to get an accurate triglyceride lab test?



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Fasting - References

References

Bjørnholt JV,Erikssen G,Kjeldsen SE,Bodegård J,Thaulow E,Erikssen J, Fasting blood glucose is independently associated with resting and exercise blood pressures and development of elevated blood pressure. Journal of hypertension. 2003 Jul     [PubMed]
Longo VD,Mattson MP, Fasting: molecular mechanisms and clinical applications. Cell metabolism. 2014 Feb 4     [PubMed]
Mattson MP,Longo VD,Harvie M, Impact of intermittent fasting on health and disease processes. Ageing research reviews. 2017 Oct     [PubMed]
Anekwe L, Fasting makes little difference to results of lipid tests. BMJ (Clinical research ed.). 2012 Nov 16     [PubMed]
Tinsley GM,La Bounty PM, Effects of intermittent fasting on body composition and clinical health markers in humans. Nutrition reviews. 2015 Oct     [PubMed]
Mosek A,Korczyn AD, Fasting headache, weight loss, and dehydration. Headache. 1999 Mar     [PubMed]
Drescher MJ,Elstein Y, Prophylactic COX 2 inhibitor: an end to the Yom Kippur headache. Headache. 2006 Nov-Dec     [PubMed]
Nakamura MT,Yudell BE,Loor JJ, Regulation of energy metabolism by long-chain fatty acids. Progress in lipid research. 2014 Jan     [PubMed]
Liang Q,Zhong L,Zhang J,Wang Y,Bornstein SR,Triggle CR,Ding H,Lam KS,Xu A, FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting. Diabetes. 2014 Dec     [PubMed]
Browning JD,Baxter J,Satapati S,Burgess SC, The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men. Journal of lipid research. 2012 Mar     [PubMed]
Secor SM,Carey HV, Integrative Physiology of Fasting. Comprehensive Physiology. 2016 Mar 15     [PubMed]
Caffa I,D'Agostino V,Damonte P,Soncini D,Cea M,Monacelli F,Odetti P,Ballestrero A,Provenzani A,Longo VD,Nencioni A, Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition. Oncotarget. 2015 May 20     [PubMed]
Torelli P,Evangelista A,Bini A,Castellini P,Lambru G,Manzoni GC, Fasting headache: a review of the literature and new hypotheses. Headache. 2009 May     [PubMed]
Özbek İpteç B,Balik AR,Yüksel S,Yilmaz FM,Yilmaz G, Hemodilution is not the only reason of difference: Comparison of fasting and non-fasting lipoproteins in paired samples. Clinical biochemistry. 2018 Nov     [PubMed]

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