Published October 2021 on YouTube

Dr. Mark Mattson on the Benefits of Stress, Metabolic Switching, Fasting, and Hormesis

1. Introduction

Biological Stress:Mark explains how organisms evolved to tolerate and benefit from stress, and how modern society has made it difficult for humans to achieve biological stress.+
Food Scarcity and Exercise:Dr. Mark explains how humans evolved to handle food scarcity and why exercise is important for coping with stress. Rhonda discusses the impact of constant access to food on overall health and how it can lead to complacency. They also touch on the benefits of exercise in increasing antioxidants and defenses in muscle cells.+
Benefits of Exercise:Dr. Mark explains the benefits of exercise on the body and brain. Exercise enhances the ability of muscle cells to clear out damaged proteins and dysfunctional organelles such as mitochondria. It also stimulates the production of intrinsic antioxidant defenses and heat shock proteins that protect other proteins from being damaged.+

2. Metabolic switch

Dr. Mark explains the difference between intermittent fasting, time restricted eating, and prolonged fasting. Intermittent fasting is an eating pattern, not a diet, that includes periods of not eating to switch to using fats and ketones. Time restricted eating compresses the eating window into a 6-8 hour period to allow for daily metabolic switching. Prolonged fasting is a longer period of not eating to induce cellular stress responses.+

3. Intermittent Fasting Insights

Intermittent Fasting Benefits:Dr. Mark Mattson discusses the benefits of intermittent fasting, including reducing resting heart rate, blood pressure, and inflammation. He also shares the results of studies on overweight asthma patients and women at risk for breast cancer, showing that intermittent fasting can have profound beneficial effects on their symptoms and health indicators.+
Intermittent Fasting Science:Dr. Mark Mattson discusses the science behind intermittent fasting, including human studies and practical prescribing advice for physicians. He also explains the initial challenges of switching to a new eating pattern and how the brain and neuroendocrine systems adapt.+
Fasting and Ketones:Mark and Rhonda discuss the neuroprotective effects of intermittent fasting and the role of ketones in protecting nerve cells against epileptic seizures. They also touch on the link between satiety and hunger hormones and the production of ketones.+

4. Metabolic Switching

Metabolic Switching:Dr. Mark explains the benefits of intermittent fasting and how it differs from a ketogenic diet. While a ketogenic diet can provide some benefits, it does not increase neural network activity like intermittent fasting does. However, a ketogenic diet enhances the activity of inhibitory neurotransmitter GABA.+
Brain Health:Dr. Mark explains how GABA and BDNF play a crucial role in brain function and how a ketogenic diet can help switch neurons to use ketones as an energy source, which generates fewer free radicals and has signaling functions that affect gene expression.+

5. Exercise and fasting

Exercise and Fasting:Dr. Mark discusses his studies on animals and the effects of combining exercise and intermittent fasting. He explains how the combination can be better than just one type of metabolic stress.+
Enhancing Brain Function:Dr. Mark discusses how the hippocampus is critical for initial associations and is a focus of dysfunction in Alzheimer's disease. Alexis found that intermittent fasting and exercise increased the number of synapses and BDNF levels, enhancing brain function.+
Fasting and Exercise:Dr. Mark discusses how intermittent fasting and exercise can increase endurance and the number of mitochondria in muscle cells. The study on mice showed that the combination of intermittent fasting and treadmill training resulted in statistically significantly better endurance and increased ketone levels.+
Fasting and Exercise:Rhonda and Mark discuss the benefits of exercising in a fasted state and the importance of switching between metabolic challenges and recovery periods. They also touch on the effects of fasting and exercise on mitochondrial biogenesis.+
Refeeding and Long-Term Fasting:Dr. Mark Mattson discusses the importance of the refeeding phase and the potential long-term consequences of overdoing fasting or exercise. He also talks about the benefits of supervised fasting for short periods of time and the frequency of fasting that would be reasonable for long-term health.+

6. Benefits of plant phytochemicals

The Benefits of Eating Plants:Dr. Mark explains how our coevolution with plants has led to our ability to digest them despite the naturally occurring pesticides they produce. He also discusses the emerging evidence that has turned the antioxidant idea on its head and emphasizes the importance of eating plants for good health.+
Chemicals for Health:Dr. Mark Mattson explains that chemicals found in fruits and vegetables that are good for health are not free radical scavengers. Instead, they trigger mild adaptive stress responses in our cells that overlap with exercise and fasting. These chemicals are concentrated in the exposed parts of the fruits and vegetables and are also found in toxins like caffeine.+
Benefits of Intermittent Fasting:Dr. Mark explains how intermittent fasting can benefit people with obesity or metabolic syndrome, but the magnitude of the benefits for healthy individuals will be less. He also discusses the chemical tomatidine found in green tomatoes and its evolutionary mechanism.+
Plant Compounds and Metabolic Switching:Rhonda and Dr. Mark discuss the benefits of metabolic switching, autophagy, and stress response pathways. While there haven't been studies on the combined effects of exercise, intermittent fasting, and plant phytochemicals, Dr. Mark believes that a mostly plant-based diet is ideal for longevity. However, it's important to maintain muscle mass as you age and not take in insufficient energy.+
Biosphere and ALS:Dr. Mark discusses the Biosphere experiment and how it relates to calorie restriction and intermittent fasting. He also shares his personal experience with time-restricted eating and the effects of intermittent fasting on a mouse model of ALS.+
Muscle Mass & Low Body Weight:Dr. Mark shares his personal experience on losing muscle mass due to an accident and emphasizes the importance of maintaining muscle mass during aging. He also warns against using exercise and fasting as a substitute for an unhealthy diet. Rhonda discusses the targeted effects of chemicals in plants compared to exercise and fasting.+

7. Safety considerations for fasting

Intermittent Fasting and Aging:Dr. Mark Mattson discusses the benefits of intermittent fasting in reducing the risk of cancer and obesity. He also talks about the lack of studies on the effects of intermittent fasting in elderly people and suggests that exercise and a healthy diet may be more important for them.+
Autism and Exercise:Dr. Mark discusses the correlation between maternal obesity and autism, and how exercise and intermittent fasting can help improve the symptoms of autism.+

8. Fasting and women's hormones

Fasting and Women:Dr. Mark Mattson discusses the effects of fasting on women, citing animal studies that show 40% calorie restriction can stop menstrual cycles, while intermittent fasting doesn't seem to have much effect. He also touches on the importance of caloric load and metabolic switching during fasting.+
Intermittent Fasting Benefits:Mark and Rhonda discuss the benefits of intermittent fasting on brain health and how it can be beneficial even without calorie restriction. They also touch on a study that shows improvement in insulin sensitivity and belly fat loss in women who practiced intermittent fasting.+
Fasting and Anorexia:Dr. Mark discusses the potential risks of intermittent fasting for adolescent girls and the unknown relationship between fasting and anorexia nervosa. He also shares his interpretation of a study on calorie restriction and fertility in rats.+
Fasting Benefits:Mark discusses the benefits of intermittent fasting on heart rate and blood pressure. Similar to aerobic exercise, fasting enhances the parasympathetic nerves that innervate the heart, causing a reduction in heart rate and blood pressure.+
Parasympathetic Benefits:Mark and Rhonda discuss the benefits of enhancing the parasympathetic nervous system through techniques such as intermittent fasting and sauna use. These methods can improve heart rate, blood pressure, and gut motility, mimicking the effects of cardiovascular exercise.+
Hormones and Aging:Dr. Mark discusses how calorie restriction can extend the age of menopause in rats and how cortisol levels increase in animals on calorie restriction. He also explains the two receptors for cortisol and their role in endocrinology.+
Cortisol and Intermittent Fasting:Mark explains how intermittent fasting affects the two different receptors for cortisol in the hippocampus of mice, and how the cells respond to stress differently with intermittent fasting compared to chronic uncontrollable stress.+

9. Fasting mimetics

Fasting Mimetics:Dr. Mark Mattson discusses the use of fasting mimetics like two deoxy glucose to activate pathways like autophagy. He also shares his personal intermittent fasting routine and the potential risks of mimicking calorie restriction.+
Fasting and Lifespan:Dr. Mark Mattson predicts that daily time restricted eating, such as eating within a six or eight-hour window, would have a positive effect on human lifespan. He explains that in animals, calorie restriction and intermittent fasting have a striking ability to extend lifespan, while exercise alone has minimal effect.+
Exercise and Intermittent Fasting:Dr. Mark shares his personal experience that exercise has more profound beneficial effects on his mental health than intermittent fasting, while Rhonda agrees that she exercises for the brain benefits and mood. They discuss the importance of exercise and how it affects the body positively.+
Neuron Excitotoxicity:Mark and Rhonda discuss how excitotoxicity in neurons can lead to neurodegeneration in diseases like Alzheimer's and Parkinson's. Mitochondrial dysfunction can cause neurons to continue to be excited even though they aren't producing enough ATP to run ion pumps. They also touch on the role GABA production from being in ketosis can play in negating this effect.+

10. Ketone esters

Ketone Esters' Potential:Dr. Mark Mattson and Rhonda Patrick discuss the potential of ketone esters in combating Alzheimer's disease. Studies have shown that ketone esters can be beneficial in reducing amyloid accumulation and neurofibrillary tangle, and may be promising for early Alzheimer's disease patients.+
Ketone Ester Benefits:Dr. Mark shares how ketone esters can benefit people with Parkinson's disease while Rhonda shares her personal experience with her mother's motor disorder and how ketone esters have improved her tremors. They also discuss how the esters can be a motivating factor for people who are not motivated to try a ketogenic diet.+
Ketone Esters:Rhonda discusses the potential benefits of using ketone esters to induce ketosis for people who are interested in trying a ketogenic diet. She also talks about how it could help with epilepsy and motor dysfunction.+