Saturday, October 1, 2022
Mitochondrial Health

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

In this episode, Dr. Mark Mattson discusses how stressing the body through exercise, fasting, and plant phytochemicals have beneficial effects on the brain and overall health.

Dr. Mark Mattson is an adjunct professor of neuroscience at the Johns Hopkins University School of Medicine and the former chief of the Neuroscience Research Laboratory at the National Institute on Aging. He is one of the most cited neuroscientists in the world, with more than 180,000 citations of his work noted in the scientific literature.

Dr. Mattson’s rigorous work has advanced scientific understanding of brain aging and identified fundamental aspects of age-related neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. His most notable work has focused on how the brain responds to mild stressors, such as those associated with exercise and intermittent fasting.

You can access the show’s notes, timeline, and transcript here:

Listen to this interview as an Apple Podcast:

Dr. Mattson’s faculty bio page:

00:00:00 – Introduction
00:11:33 – Metabolic switch
00:16:14 – Different types of intermittent fasting
00:29:37 – Benefits from a ketogenic diet vs fasting
00:38:18 – Exercise and fasting
00:59:07 – Benefits of plant phytochemicals
01:25:18 – Safety considerations for fasting
01:34:43 – Fasting and women’s hormones
02:03:42 – Fasting mimetics
02:18:51 – Ketone esters


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40 thoughts on “Dr. Mark Mattson on the Benefits of Stress, Metabolic Switching, Fasting, and Hormesis
  1. In this episode, we discuss…
    00:01:15 – How biological stressors drive adaptation and prevent physiological complacency.
    00:11:33 – How intermittent fasting confers many health benefits by physiologically stressing your metabolism and causing a switch from burning carbohydrates to fat.
    00:16:14 – Comparing the differences and similarities of daily time-restricted eating with 5:2 weekly intermittent fasting.
    00:23:25 – How after a couple of weeks of metabolic adaptations, intermittent fasting gets more manageable.
    00:29:37 – Comparing the different effects of a ketogenic diet and intermittent fasting on the brain.
    00:38:18 – Whether or not there is an additive effect of exercising while intermittent fasting.
    00:52:08 – The importance of re-feeding after a fast.
    00:56:04 – The fasting duration and frequency necessary for sustained health benefits
    00:59:07 – How co-evolving with plants has led to the evolution of many metabolic pathways that respond to plant chemicals.
    01:07:33 – How green tomatoes contain a natural compound called tomatidine that deters insects but is good for human health.
    01:09:32 – Does diet matter if you are already doing intermittent fasting and exercising?
    01:14:14 – How much can a healthy person benefit from intermittent fasting.
    01:18:54 – Caloric restriction to an extreme can be bad and compromise muscle mass.
    01:22:21 – Mattson's personal anecdote of not building enough lower body strength.
    01:25:18 – Safety considerations of intermittent fasting in the elderly, children, and pregnant women.
    01:29:46 – Mattson speculates why autism has grown exponentially in our society.
    01:34:43 – How fasting affects women's hormones and menstrual cycle.
    01:52:04 – Uncoupling the benefits of caloric restriction and intermittent fasting
    01:57:57 – How Intermittent fasting has beneficial effects on cardiovascular health.
    02:03:42 – Mattson's opinions on fasting-mimetics like resveratrol and spermidine.
    02:09:30 – Dr. Mattson's perspectives on whether intermittent fasting can, in a practical sense, extend lifespan or healthspan in an already healthy person.
    02:14:31 – Mattson's upcoming book, "Sculptor and Destroyer: The story of glutamate. The brain's most important neurotransmitter."
    02:18:51 – How ketone supplementation may improve brain health.

  2. Not surprised he's having issues with trying to build back his muscle mass, given that he's 'mostly plant based with SOME fish'- ? He doesn't really say what his daily exercise IS? If he's still doing mainly cardio and not much resistance training – again…not surprised (combined with his PB diet) that he's challenged in building muscle mass.
    Unsure why he went right to 'taking Rapamycin' – rather than taking NR or NMN? Who takes Rapamycin, anyway? I think it's basically a bad idea.

  3. Wonderful information! I have to say though, and not at all to be disrespectful, but I first listened to this podcast and thought Dr. Mattson was quite a bit older than he is. He appears very frail. I know that you only interview scientists but there are regular people out there who are changing the face of aging that should get some attention. Wendy Ida, Chuando Tan, Takimika. I have yet to see a longevity researcher who appears truly to have defied aging. Perhaps it is Rhonda! Michael Lustgarten too!

  4. I have an interesting N of 1 case. I'm 70 5'10 Weigh 70Kg – HIIT and HIRT 3 x per week. IF 18:6 every day and Keto diet – no fruit, cruciferous veg including sourkrout egg yolks, high fat yoghurt, hard cheese, meat and fish. MCT powder with 3 coffees a day. All for over 5 years. My GlycanAge Test came back at a biological age of 32. I'm about to take a gene test. I also take a supplement stack every day.

  5. Thanks again Dr Rhonda Patrick for hitting another home run – out of the medical ball park.

    So sad to hear of Dr Mark Mattson’s personal injuries.

    Two brilliant minds at work. I surprised at your many insightful questions, to which Dr Mattson had already done specific research to fully address your question. How many experiments must he have performed during his brilliant career? Dr Mattson has a passion for seeking out the truth. So do you Dr Rhonda Patrick.

    I hope you or he are not retiring soon.

  6. Very informative, thank you ! Just wanted to share the following. My average HRV (via Oura Ring) is around 65ms with daily swings +/- 30 ms depending on amount/intensity of exercise and recovery. The night after my first Pfizer vaccine my HRV it plummeted to 15 ms! Even though I had no reaction to the jab, In a way the drop in HRV was re-assuring to me as I assumed that it indicated that my sympathetic NS was being activated and my immune system was actually "in gear"

  7. As always, great content Rhonda! Please consider significantly lowering the release time on the gate and/or noise reduction stage on your guests' audio to reduce the noise pumping artifact. If you are compressing, then try moving that to before the noise cancelation in the chain. The interview audio here is leaps and bounds above most recorded video interviews around the web regardless. Thank you!

  8. Thank you, That’s very interesting. Can we call “addiction to the food” what is happening nowadays? I suffer for not to get fat, I can’t relax, if I do I have non stop. I am not even hungry, I am just addicted! Anyone else?

  9. If calorie restriction had little or no effect on the longevity of long lived species such as monkeys, why would we think that IF or calorie restriction would have a significant effect on human life span. It's much more likely to affect human health span.

  10. Great discussion Rhonda and Mark! And, if I am not mistaken, I think rates of body dysmorphia have greatly increased. However, clinical rates of anorexia have pretty much stayed stagnant.

  11. Intermittent fasting is the easiest way to stay at a healthy weight. Eat in an 8 hour window or less. Thats all you need to do as a beginner. No need to be a nutrition expert, or watch calories. Once thats nailed down, you can play with your circumstances as far as days off, or training while fasted etc. Just start with 8 on 16 off. Aside from getting good sleep, its the single most effective way to getting healthier. Even more than exercise.👍

  12. A question: at 38:00 he is talking about thé signaling functions of the ketones, but they are less then exercise and intermittent fasting, to keep the brain working/ healthy.
    So the question is : therefor keto diet is not that helpful for the brain ?

    Should one exercise and intermittent fasting and also let our brain run on carbs/ glucose one would do well, for the brain?

  13. im torn between 2 meals a day and 3 meals a day. it seems eating 2 large meals a day, especially if one is an athlete who is gaining weight/muscle, that one would have to eat a lot of calories in one sitting and im not sure how beneficial this is compared to three meals if both types of eating are done within the same time window. especially with 2 meals, one would have to partition a good amount of calories to the evening in order to not be eating a ton of calories in one sitting, which has been shown to not be advantageous to a good nights sleep and overall circadian/digestion health. im interested in seeing a study done comparing these meal frequency

  14. Amazing information!! Thank you so much for the details printed out too, to refer to. The science is just great. The work you do is so valuable!! I hope your parents do better.

  15. Very engaging information on Fasting, Ketones & Metabolic flexibility. Sadly real scientific discoveries on human health & longevity are not assimilate well into the medical field. There are blocks from big pharmaceutical & food companies to influence medical as there is no profit from much benefits of fasting.
    I am on Fasting, Low Carbohydrate, Supplement & Body Workout since 3 years ago & enjoying all the benefits mentioned here. Thanksgiving for this great interview.

  16. Rhonda is becoming better and better at this! I love the short outline at the begining. The big picture is helpful for keeping track and understanding the details. The literature quotations at the bottom of the screen was very useful too. I can't imagine how much work went into this. Thank you for being awesome Rhonda!

  17. With the toxicologic history of increased body burden in bone of the toxic metal lead across the population, lead perturbs many of the same physiologic systems that are being talked about here. GABA can be reduced very significantly with lead exposure. Cytochrome P450 system can be harmed, glutamate systems can become more hyperactive, and bone sequestered lead can become mobilized again when the body enters stressed conditions such as old age, illness, or pregnancy, as the body seeks to get more calcium. Since this happens just when the body is most vulnerable. How does lead toxic exposure through life play into the risks being discussed. Our bones have hundreds to thousands of times the lead content than prehistoric bones had, now when it comes out into soft tissue again doesn't it become another comorbidity? Is there research lit that clarifies intermittent fasting when people over seventy try to become more insulin sensitive again and lose weight?

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