Fasting, Food, Folates and the Sun Bernie Hendricks, R.Ph. CE - PowerPoint PPT Presentation

“Fasting, Food, Folates and the Sun” Bernie Hendricks, R.Ph. CE Coordinator South Dakota State University College of Pharmacy and Allied Health Professions Brookings, SD

Disclosure:  I have no financial relationships to declare.

1.0 hr – ACPE credit  Pharmacists:  #0063-9999-19-050-L04-P  Tecjnicians:  #0063-9999-19-050-L04-T  September 13, 2019

Pharmacist Learning Objectives 1. Explain the triggering mechanisms for autophagy and mitophagy; 2. Describe the structural changes that occur during starch retrogradation, and explain the resulting nutritional benefits of following those changes; 3. Identify two major nutritional benefits of folates, and identify potential absorption problems; 4. Evaluate the potential benefits of chronic, low-intensity UVR exposure.

Technician Learning Objectives 1. Define the terms autophagy and mitophagy; 2. Describe the nutritional benefits of starch retrogradation; 3. Name three folate supplements, and identify major food groups that are high in folate nutritional value; 4. Explain the potential benefits of moderate daily sunshine.

Goal of this presentation Improve the personal health profile of pharmacy professionals themselves.

Alternate title: “Fun, Food (deprivation), Fast-Food, Folates and the Sun”

Motivational Quotes…

“If I had known I was going to live this long, I would have taken better care of myself.” -Unknown

“As for me, except for an occasional heart attack, I feel as young as I ever did.” - Robert Benchley

Food deprivation - “Fasting”…  Introduction

Glossary Autophagy (self-devouring): Segregation and disposal of damaged organelles within a cell.

Glossary Mitophagy: Mitochondrial selective autophagy -surveils mitochondrial population, eliminating superfluous and/or impaired organelles and mediating cellular survival and viability in response to injury/trauma and infection.  Front. Immunol., 05 June 2018 | https://doi.org/10.3389/fimmu.2018.01283  Accessed from: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01283/full

Fasting – triggers autophagy and mitophagy  Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We surmise that there are 3 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the inhibition of acetyltransferases, which are enzymes that transfer acetyl groups from AcCoA to other molecules, mostly leucine residues in cellular proteins, or (iii) the stimulation of deacetylases, which catalyze the removal of acetyl groups from leucine residues.  There are several examples of rather nontoxic natural compounds that act as AcCoA depleting agents (e.g., hydroxycitrate), acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine) or deacetylase activators (e.g., nicotinamide, resveratrol), and that are highly efficient inducers of autophagy in vitro and in vivo, in rodents. Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage. Hence, we classify them as "caloric restriction mimetics" (CRM).  Here, we speculate that CRM may mediate their broad health-improving effects by triggering the same molecular pathways that usually are elicited by long-term caloric restriction or short- term starvation and that imply the induction of autophagy as an obligatory event conferring organismal, organ- or cytoprotection.  Autophagy. 2014;10(11):1879-82. doi: 10.4161/auto.36413.  Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers.  Mariño G 1 , Pietrocola F, Madeo F, Kroemer G.  https://www.ncbi.nlm.nih.gov/pubmed/25484097

Fasting – triggers autophagy and mitophagy Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins.  Autophagy. 2014;10(11):1879-82. doi: 10.4161/auto.36413.  Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers.  Mariño G 1 , Pietrocola F, Madeo F, Kroemer G.  https://www.ncbi.nlm.nih.gov/pubmed/25484097

Fasting – triggers autophagy and mitophagy There are several nontoxic natural compounds that are “highly efficient inducers of autophagy in vitro and invivo in rodents”: 1. AcCoA depleting agents (e.g., hydroxycitrate), acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine) 2. deacetylase activators (e.g., nicotinamide, resveratrol), and that are highly efficient inducers of autophagy in vitro and in vivo, in rodents.  Autophagy. 2014;10(11):1879-82. doi: 10.4161/auto.36413.  Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers.  Mariño G 1 , Pietrocola F, Madeo F, Kroemer G.  https://www.ncbi.nlm.nih.gov/pubmed/25484097

Fasting – triggers autophagy and mitrophagy  Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage. Hence, we classify them as "caloric restriction mimetics" (CRM).  Here, we speculate that CRM may mediate their broad health-improving effects by triggering the same molecular pathways that usually are elicited by long-term caloric restriction or short- term starvation and that imply the induction of autophagy as an obligatory event conferring organismal, organ- or cytoprotection.  Autophagy. 2014;10(11):1879-82. doi: 10.4161/auto.36413.  Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers.  Mariño G 1 , Pietrocola F, Madeo F, Kroemer G.  https://www.ncbi.nlm.nih.gov/pubmed/25484097

Autophagy - Exercise “Exercise and exercise training induced increased autophagy markers in human skeletal muscle” “…exercise increases markers of autophagy in human skeletal muscle within the first 2 h of recovery and 8 weeks of exercise training increases the capacity for autophagy and mitophagy regulation.” Physiol Rep. 2018 Apr;6(7):e13651. doi: 10.14814/phy2.13651. Accessed: https://www.ncbi.nlm.nih.gov/pubmed/29626392

Mitophagy – Innate Immunity  “Defective removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and subsequently to chronic systemic inflammation and development of inflammatory diseases.”  Mitophagy has a critical role in the “innate immune system homeostasis.”  Front. Immunol., 05 June 2018 | https://doi.org/10.3389/fimmu.2018.01283  Accessed from: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01283/full

“System-wide benefits to intermeal fasting by autophagy”  “Our studies suggest that consuming two meals a day with complete food restriction in between the meals is sufficient to lower blood glucose and lipid levels. This simple dietary approach activates a cell “cleansing system” called autophagy in liver, fat, brain, and muscle that helps prevent obesity and diabetes.”  Accessed from:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718973/

“ The Fasting Cure is No Fad” Wall Street Journal, Aug 1, 2019 https://www.wsj.com/articles/the-fasting-cure-is-no-fad- 11564676512 —Dr. Michalsen is a professor at Berlin’s Charité University Medical Center. This essay is adapted from his new book, “The Nature Cure: A Doctor’s Guide to the Science of Natural Medicine,” which Viking will publish on Aug. 6.

Michalsen: “Scientific evidence for the glory of breakfast is scarce. Instead, we should skip it and eat lunch like kings.”

Michalsen: “At the Charité University Hospital in Berlin, I’ve employed what’s called intermittent fasting, or time-restricted eating, to help patients with an array of chronic conditions. These include diabetes, high blood pressure, rheumatism and bowel diseases, as well as pain syndromes such as migraines and osteoarthritis.

Michalsen: “… omit either dinner or breakfast.. don’t ingest any food for at least 14 hours at a stretch. That makes lunch the most important meal of the day. It also reduces the time spent each day processing food and lengthens the period devoted to cleansing and restoring the body’s cells, both of which have positive health effects”

Michalsen: “Adopting this technique is not as difficult as it may seem. If you sleep from 11 p.m. to 7 a.m., you’ve already fasted for eight hours. Now you only need another six. It’s healthy to avoid eating late in the evening to let your body burn energy from food rather than store it, so if you eat dinner by 7 p.m., that’s another four hours. For breakfast, you can limit yourself to coffee or tea (maybe with a small piece of fruit) and make lunch your first proper meal. By that time, you’re clearly beyond the 14 hours and don’t need to restrain yourself: You can eat until you are full.