July 2, 2018


Rhonda Patrick, Ph.D.: the performance and longevity paradox of IGF-1, ketogenic diets and genetics, the health benefits of sauna, NAD+, and more (EP.02)

If you’re doing something of quality, and are passionate about it, and you put in the work, people will notice it. — Rhonda Patrick

by Peter Attia

Read Time 3 minutes

Rhonda Patrick, Ph.D. and I go on a Nerd Safari into the jungle of health, nutrition, fitness, performance, and longevity. We visit IGF-1 and whether there’s a tradeoff between having high or low levels. We discuss the PPARs (receptor proteins) and genetic polymorphisms. Does Rhonda think there’s any benefit in a NAD+ booster for health and longevity? Can saunas lower the risk of heart disease, dementia, and all-cause mortality? We dig into those questions…and a lot more.


Rhonda is a wealth of knowledge and was the perfect companion to explore several interesting topics in this episode. She puts a great deal of thought and effort into her research, and it really shows in this conversation.

We discuss:

  • What Rhonda believes differently today than she did a few years ago;
  • The paradox of GH/IGF-1 in performance and longevity;
  • The role of PPAR in fat metabolism and ketogenic diets;
  • The possible genetic explanations for why some patients don’t respond well to a ketogenic diet;
  • The health benefits of heat and cold exposure;
  • NAD+; and
  • More.

Show Notes

What Rhonda believes differently today versus 5 years ago? [5:40]

Calorie restriction and IGF reduction. Is it the best way to boost longevity? [6:30]

Rhonda’s changing opinion on the ketogenic diet. [9:00]

Peter’s experience with the ketogenic diet [10:30]

Exogenous ketones: Rhonda’s personal experience. [13:00]

Diet-induced ketosis, purported benefits and detriments, limitations of current studies, and what Peter would like to see in a future study. [15:30]

The practicality of the ketogenic diet and how to get your nutrients. [16:45]

The IGF-1 paradox, is it “good” or “bad?” [21:00]

Misconceptions about protein levels in the ketogenic diet. [22:00]

Intro to PPAR alpha and PPAR gamma, polymorphisms that impact fatty acid metabolism, ketogenesis, and how we react to saturated fat. [23:00]

Saturated fat and genetic variants that may affect how we respond to consuming it. [25:30]

How certain genes variants may affect certain people’s reaction to saturated fat. [29:00]

Rhonda has developed a genetic testing tool available to the public. [30:00]

Why some people have trouble producing ketones and how exercise and fasting may be the crucial piece for getting over the hump. [31:00]

Rhonda’s approach to eating/fasting/exercise and using exogenous ketones by HVMN. [34:45]

Can ketone esters be used to reduce blood glucose levels? [41:15]

Acarbose for controlling blood glucose. [41:45]

Peter and Rhonda share their evolving understanding of the IGF-1 literature. [42:15]

Only the germ cells in C. elegans divide, which may make cancer in this organism fundamentally different than humans. “Nematodes have a fixed, genetically determined number of cells, a phenomenon known as eutely. The adult hermaphrodite has exactly 959 cells. The male C. elegans has 1031 cells. The number of cells does not change after cell division ceases at the end of the larval period, and subsequent growth is due solely to an increase in the size of individual cells.” [Wikipedia]

Do we want low or high IGF-1? Or is “cycling” the key? [48:00]

Figure. Predicted HR for the association between IGF-I and all-cause mortality. [Burgers et al., 2011]

Image credit: Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality (Burgers et al., 2011)

Figure. Relationship between serum IGF-1 levels and risk of (A) all-cause mortality (B) cancer mortality and (C) cardiovascular disease (CVD) mortality. [Svensson et al., 2012]

Image credit: Both Low and High Serum IGF-I Levels Associate with Cancer Mortality in Older Men (Svensson et al., 2012)

The important role that IGF-1 plays in muscle and brain tissue through exercise. [50:00]

Efficacy of prolonged fasting for cancer, autoimmune diseases, and other afflictions. [51:00]

Prolonged fasting and cancer, how it could maybe be apart of standard of care in the near future. [53:00]

Can chemo patients benefit from fasting and certain dietary protocols? [54:15]

Can fasting help with the response to, and recovery from, invasive operations? [55:00]

Importance of exercise for brain health. [59:30]

VO2 max, cardiorespiratory fitness, strength training, and how it affects our health. [1:03:15]

Can lowering inflammation be a key to extending life? [1:06:30]

Peter shares his hope/vision for the future of personalized health protocols. [1:11:45]

Sauna, and the growing evidence for the benefits of heat therapy. [1:12:30]

Does sauna have an impact on sleep? [1:13:30]

Saunas and the healthy-user bias, a critical look at the literature. [1:14:15]

The overlapping physiological responses of heat therapy and exercise. [1:16:15]

Saunas as an antidepressant? [1:17:15]

Different types of saunas and which one Rhonda likes best. [1:18:15]

Can saunas act as an anti-inflammatory and improve insulin sensitivity? [1:20:15]

Can saunas help prevent neurodegeneration? [1:21:45]

What kind of disease is dementia? And how might ketones and saunas help? [1:22:15]

Cold therapy vs heat therapy, similarities, and differences. [1:24:30]

Can we stack hot and cold therapy to maximize the benefits? [1:28:30]

Cold therapy and mitochondrial biogenesis. [1:29:00]

How cold therapy can blunt hypertrophy from strength training. [1:31:15]

A primer on NAD+/NADH, its effect on lifespan/healthspan, and a review of the supplements. [1:32:45]

PARP, an important enzyme for DNA repair, needs NAD+ for fuel. [1:34:30]

What causes NAD+ to decrease as we age? [1:35:00]

Could metformin negatively affect the NAD+ to NADH ratio? [1:36:15]

Evidence for NAD+ supplements. [1:37:00]

Can we increase NAD+ levels with fasting? [1:38:00]

Peter asks Rhonda, “What is the most interesting question you don’t yet know the answer to but you feel like is knowable?” [1:39:15]

Rapamycin, the most promising life-extension drug? [1:42:30]

The next medical frontier: specificity and selectivity of drugs. [1:45:00]

Where you can find Rhonda and her work. [1:46:45]

Selected Links / Related Material

People Mentioned

Rhonda Patrick, Ph.D.

Rhonda Perciavalle Patrick has a Ph.D. in biomedical science from the University of Tennessee Health Science Center, Memphis TN and St. Jude Children’s Research Hospital, Memphis TN. She also has a Bachelor’s of Science degree in biochemistry/chemistry from the University of California, San Diego. She has done extensive research on aging, cancer, and nutrition. She did her graduate research at St. Jude Children’s Research Hospital where she investigated the link between mitochondrial metabolism, apoptosis, and cancer. Her groundbreaking work discovered that a protein that is critical for cell survival has two distinct mitochondrial localizations with disparate functions, linking its anti-apoptotic role to a previously unrecognized role in mitochondrial respiration and maintenance of mitochondrial structure. Her dissertation findings were published in the 2012 issue of Nature Cell Biology.

Dr. Patrick trained as a postdoctoral fellow at Children’s Hospital Oakland Research Institute with Dr. Bruce Ames. She investigated the effects of micronutrient (vitamins and minerals) inadequacies on metabolism, inflammation, DNA damage, and aging and whether supplementation can reverse the damage. In addition, she also investigated the role of vitamin D in brain function, behavior, and other physiological functions. In February of 2014 she published a paper in FASEB on how vitamin D regulates serotonin synthesis and how this relates to autism.

Dr. Patrick has also done research on aging at the Salk Institute for Biological Sciences. At the Salk she investigated what role insulin signaling played in protein misfolding, which is commonly found in neurodegenerative diseases.

She frequently engages the public on topics including the role micronutrient deficiencies play in diseases of aging, the role of genetics in determining the effects of nutrients on a person’s health status, benefits of exposing the body to hormetic stressors, such as through exercise, fasting, sauna use or heat stress, or various forms of cold exposure, and the importance of mindfulness, stress reduction, and sleep. It is Dr. Patrick’s goal to challenge the status quo and encourage the wider public to think about health and longevity using a proactive, preventative approach. [ FoundMyFitness.com]

Rhonda on Facebook: FoundMyFitness

Rhonda on Instagram: @foundmyfitness

Rhonda on Twitter: @foundmyfitness

Rhonda’s website: FoundMyFitness.com

Rhonda’s podcast: FoundMyFitness

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.


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  • Charley Mitchell

    Excellent show here! Thank you both for this fascinating conversation. I look forward to more shows with Dr. Rhonda Patrick.

  • Chaz

    This was an amazing podcast – incredibly wide ranging series of topics. I first discovered you back in 2011 and I’d say a ferocious amount of what I know scientifically/medically come from things I’ve learned over the years in various incarnations (and investing the needed time to understand appropriately). Look forward to more great info and insight!

  • Nikolai Peterson

    Great podcast, will definitely be adding to the list of staples. I’ve been a long time follower of both of you and have put many of your suggestions pertaining to longevity into action. Unfortunately, I just got diagnosed with T1D a week ago at the age of 21. After having doctors, nutritionists, and “diabetes educators” tell me while I was in the hospital that my diet shouldn’t be changed and I should just cover the carbs with insulin. I was quick to double check the ol’ google scholar to make sure I wasn’t crazy, because this didn’t sound like the most current advice. I’ve already constructed a much better diet for myself, but I am concerned about longevity as it pertains to T1D. I know you can’t give direct medical advice here, but I was wondering if you could lay out conceptually how the customary advice of “keep a low average level of glucose and a low variance of glucose and a low insulin curve integral” changes for a T1D? Or just more generally, how can people with T1D get that decade that most lose on average? I know you’re a busy man but I’d really appreciate it if you could touch on this in a post or a comment at some point. Thanks so much for all you do.


      Read Richard K. Bernstein, The Diabetes Solution.

  • Manuel Riel

    Learnt a lot from the part on high-fat/keto diets and genetics. My first year of keto went very badly (high LDL, high TG/HDL ratio, small LDL particle size). After moderating dairy it got better. Rhonda’s genetic report will show you the relevant SNPs. (rs9939609 and rs17817449).

  • Mark Kelman

    I detect a clear lack of confidence in Aubrey and his cronies : )))) Perhaps Peter could attend the longevity conference next week on the 12th in NYC. Maybe even ask a couple questions : / https://www.leafscience.org/ending-age-related-diseases-advances-in-aging-research-and-investment-prospects/

  • Dan Leslie

    Excellent podcast! It looks like there are substantial benefits to be gained from prolonged fasting but I am concerned about immune memory. Valter Longo has shown that the immune system is pared down and then rebuilt after a 3-day fast. Are old memory T cells that have been primed for action by immunization or disease lost in the paring process? I would like to have a rebuilt immune system but don’t want to lose a lifetime of acquired immunity.

    • orbifold

      Hold on, would you be able to regenerate the entire immune system to the extent of “curing” common autoimmune diseases, like gluten intolerance, by prolonged fasting?

  • philip martin

    Hi Peter, thank you for all the wonderful information you provide. I’m seeking further information (not medical advice!) about two topics you touched on with Rhonda Patrick, on both your podcast and hers. First is rapamycin — we have experts on both sides arguing for and against taking it. What evidence would you want to see in trials before you would consider it a possible viable treatment for people 60+? Are we getting close or still miles away? Second, regarding mTORC1 you mentioned on Rhonda’s blog that people with muscular dystrophy ‘want to figure out how to alter that pathway.’ As a friend of mine was recently diagnosed with MD, is there a link or resource you would recommend for information on this that she could show her doctors? Many thanks in advance.

  • blipton

    Valter Longo’s interview on the HIH podcast mentions (30m12s mark), how fasting above 12 hours and/or skipping breakfast, is associated with gallstones, and overall mortality! Any thoughts on this?

    Regarding the 54m mark, what might the diet of a cancer patient look like in the future… 24-48 hours of fasting prior to chemotherapy, then normal eating immediately after the procedure?

    Regarding how a larger/faster drop in body temperature just before going to bed may lead to better sleep [1h3m], I must be like those piglets.. I dream a lot more when the electric blankets are set to hot!

    If taking an anti-inflammatory an hour after workout is counter-productive, would a cold shower after the sauna be potentially un-doing some of benefits of the heat exposure (HSPs, etc)?

    I’ve heard how infrared exposure is able to heal injuries quicker, and according to Dave Asprey infrared saunas may help with mitochondrial function. It was mentioned Peter will ask Navdeep Chandel about whether or not metformin impairs NAD/NADH, can you post his response?

    I like the idea that just twenty-four 45-min sessions can un-do 10 years of declining vvo2max in the brain [1h3m].. I wonder how often the reset would have to be performed!

  • Tokto Vanichstian

    This is one hella show notes!


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