Autophagy and Fasting: Its effect on disease and how fasting may help

Fasting

The Muslim Times has the best collection of articles about fasting and the utilitarian value of the teachings of Islam.  Suggested reading: Most U.S. Muslims observe Ramadan by fasting during daylight hours

By Dr. Lutf ur Rehman, Nashville, USA

We believe as Muslims that God’s creation is perfect. God has made this claim in the Holy Quran:

You see not any imperfection in the creation of the Gracious God. Look again! Do you see any flaw? Look again and again. Your gaze comes back to you dazzled, perplexed, and fatigued, having found no incongruity. (Al Mulk 67:4-5)

The human body is made of billions of cells of different kinds. Cellular structure and function can be compared to a factory. There are many different departments, all of which have a specific task and work in cooperation with each other. Waste is created and cleared. An amazing process continues until the death of the cell. Some cells are replaced, but others cannot be replaced. Over time, as cells degrade, we develop illnesses such as diabetes and cancer. The aging of cells ultimately leads to death.

Each cell is so complex that even after centuries of study, scientists are still trying to understand and discover amazing processes within cells. Like any functioning machine, parts of cells can be damaged and need removal and replacement. God has created processes within the cells to accomplish this task. In 2016, Japanese scientist Dr. Yoshinori Ohsumi was awarded a Nobel Prize for discovering and detailing the process of autophagy and the genes controlling this process.

Autophagy supports vital activity by recycling proteins inside cells. This mechanism was discovered by Dr. Yoshinori Ohsumi in the 1990s. This process is fundamental to supporting our body’s vital activity. A cell has many components called organelles. These include the nucleus, mitochondria, endoplasmic reticulum, Golgi bodies, etc. These are all vital for the normal function of the cell. If one of them or part of them becomes defective, it needs to be removed and replaced for maintenance of normal cellular function. The process of autophagy accomplishes this task.

The process works like this. When an organelle of the cell (such as mitochondria or endoplasmic reticulum) is damaged, it is marked by a protein. This triggers the formation of a membrane which envelops the damaged organelle. This complex then merges with a self-enclosed compartment known as a lysosome. Degrading enzymes within the lysosome are then activated, and the damaged organelle is broken down to its component amino acids. These are then released into the cell and used to build the cell again. The body generally needs about 200 grams of amino acids every day. Food can supply less than half of this (about 70 grams), while the rest comes from recycled cellular components.

Dr. Ohsumi explained this process by using baking yeast in his research. Yeast cells have the same structure as human cells, and they contain the same organelles, including a nucleus, endoplasmic reticulum, and mitochondria. Majority of the yeast is compiled of a vacuole. Dr. Ohsumi focused on this vacuole. He believed that it has some connection with autophagy that breaks down proteins. The fact that the vacuole in the yeast contains a large amount of degrading enzymes was already known. That is why researchers believed that the vacuole functions like a breakdown compartment. Ohsumi tried to observe what was happening in a strain of yeast with a genetic mutation that did not have the ability to breakdown proteins. He found that in the normal state he could not see any changes in the vacuoles. However, he was able to see a dramatic change when nutrients were not given to the yeast. Small particles could be seen inside the vacuoles in a state of starvation. This was a decisive moment as it was something that could be seen particularly because the yeast did not have the degrading enzymes. From this result the ground breaking system of how proteins are broken down became clear. When the yeast enters into a state of starvation a sac like membrane appears inside the cell. It envelops the proteins that are in the cytoplasm. This moves to the vacuole with the protein. When this happens the degrading enzymes inside the vacuole start working, which is the mechanism how proteins are broken down. Yeast in which autophagy is working normally can live for about one week. However if the autophagy does not work the yeast dies. This is same as with humans. Our cells are constantly breaking down proteins. The process of repair and replace goes on.

If the process of autophagy does not work properly or fails, what can happen? Many diseases are attributed to a defect in the process of autophagy. Fifteen genes in the human genome have been discovered which regulate one part or another of the process of autophagy. A defect in any one of them will cause some defect in the process leading to illness. Following is an incomplete list of illnesses which are now attributed to one or more defects in autophagy.[I]

1)      Risk and prognosis of breast, ovarian, prostate, and colorectal cancer

2)      Early onset of breast cancer

3)      Increased risk of Crohn’s disease

4)      Asthma

5)      Increased risk of systemic lupus erythematosus

6)      Early onset Parkinson’s disease

7)      Increase risk of Ulcerative Colitis

8)      Amyotrophic lateral sclerosis (ALS)

9)      Many neurodegenerative diseases

10)  Alzheimer’s disease

Research is now focusing on chemicals that can be used to increase or regulate autophagy by using them as medicines. So far, there is no sure success. But there is a simple, safe, and inexpensive method of increasing autophagy in many organs such as the liver, brain, and others. It is food deprivation, better known as fasting.[ii]

In 2010, a study was published in the journal Autophagy and described increased autophagy activity in mice models due to starvation. It demonstrated that short-term food restriction induced a dramatic upregulation of autophagy in cortical and Purkinje neurons.[iii]

In vitro models have shown that starvation in neuronal cell lines can remove toxic molecules and damaged mitochondria from neurons.[iv]

Other tissue culture studies of mutant huntingtin and α-synuclein proteins (which are associated with Huntington disease and familial Parkinson disease, respectively), have identified autophagy substrates that can be removed by drug-induced enhancement of autophagy. Most importantly, some neuroprotective effects of drug-enhanced autophagy also have been observed in vivo in a D. melanogaster model of Huntington disease.[v]

It has been suggested that intermittent fasting might improve neuronal function by means that are entirely independent of caloric intake, and may instead reflect an intrinsic neuronal response that is triggered by fasting. (Anson RM, et al. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake.[vi]

Caution is counseled, however, because studies in rat brain have suggested that chronic starvation might inhibit autophagy, an outcome that could damage, rather than protect, neurons. (Hanahisa Y, Yamaguchi M. Characterization of calcium accumulation in the brain of rats administered orally calcium: the significance of energy-dependent mechanism.[vii]

Another study conducted at the Washington University School of Medicine in St. Louis, Missouri, demonstrated the benefits of fasting-induced autophagy on heart ischemia. Mice that were fasted showed less ischemia, smaller infarcts, and better cardiac muscle function compared with control-fed mice.[viii]

Cancer is becoming more common these days. Many factors are blamed for its increasing incidence. Research has shown that excessive adiposity, decreased physical activity, and unhealthy diets are key players in the pathogenesis and prognosis of many common cancers. In addition, calorie restriction – without malnutrition – has been shown to be broadly effective in cancer prevention in laboratory strains of rodents. Adult-onset moderate caloric restriction also reduces cancer incidence by 50% in monkeys. Many effects of caloric restriction are cited as reasons for cancer reduction, one of them being autophagy. (Calorie restriction and cancer prevention: metabolic and molecular mechanisms.[ix]

Multiple studies on animals in the lab and published in Nat Cell Biology, Autophagy, and Cell Death and Disease have linked longevity with increased autophagy due to caloric restrictions.

Fasting and intermittent fasting are gaining popularity these days as a weight loss or detox tool. There is still no consensus on how to fast or reduce caloric intake. There are many questions: How long should the fast be? (16 hours, 24 hours, 3-5 days, etc.) Should it be a dry fast (without water) or wet fast? Should any calories be allowed or not? How long should the fasting continue? (5 days, 1 week, 3 weeks, etc.)

One thing is beyond dispute. God has always prescribed fasting through his Prophets. Christians, Muslims, Jews, Buddhists, and Hindus all prescribe fasting in one form or another. With time, the practice of fasting has changed in different religions, hence the differences we see today. I believe that the initial teaching of fasting was the same in all religions as it is in Islam these days.

The Muslim fast seems to be gaining more support from scientific evidence for being healthy and useful in terms of health, disease prevention, and improved longevity – more so than any other form of fasting. Some components of fasting are becoming clear:

1)      There should be severe or complete restriction of caloric intake.

2)      The fast should continue for a number of hours to be beneficial.

3)      The fasting should be continued intermittently over a period of days or weeks.

4)      The fast should not be too long or it will cause harm.

5)      Adults should fast, not children.

6)      Constant fasting for more than few weeks will be harmful

In Islam, all forms of worship not only provide spiritual benefits, but they are also beneficial in terms of physical health, psychological wellbeing, and social and cultural harmony. This is why God has called this religion, “The religion in perfect harmony with the nature.” All of its tenets improve human condition.

Research on autophagy is ongoing and will continue to reveal its results. But one cursory look at the cell’s intricate and detailed structure and complex function is enough to fill a person with awe and inspiration that indeed the creation of Gracious God is perfect.

References

[i] Peidu Jiang & Noboru Mizushima. Cell Research 24, 69-79, 2014.

[ii] Martinet W, De Meyer GR. J Histochem Cytochem 2006; 54:85-96.

[iii] (Mehrdad Alirezaei, J. Lindsay Whitton Vol. 6, 2010.

[iv] Jaeger PA, Wyss-Coray T. All-you-can-eat: autophagy in neurodegeneration and neuroprotection. Mol Neurodegener 2009; 4:16.

[v] Sarkar S, et al. Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat Chem Biol 2007; 3:331 – 338.

[vi] Proc Natl Acad Sci USA 2003; 100:6216 – 6220.

[vii] Mol Cell Biochem 1996; 158:1 – 7.

[viii] Autophagy, Volume 11, 2015.

[ix] Trends Pharmacol Sci. 2010 Feb; 31(2): 89–98.

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