Dr. Rhonda Patrick on Exercise | Joe Rogan Experience

Benefits of Exercise

(Episode 568) 2:54:06 – Dr. Patrick describes the huge benefits exercise has on top of the popular association with weight loss that exercise typically has. There is much more being done to benefit the body beyond weight loss. One study has shown that exercise detoxifies the muscles of a compound known as kynurenine (a byproduct of tryptophan metabolism). When there is too much kynurenine, some of it can get into the brain and form quinolinic acid, which is a neurotoxin responsible for multiple negative cascading effects. Exercise converts kynurenine into a form that cannot cross the blood brain barrier.

(Episode 568) 2:55:03 – More on kynurenine. A study has shown that mice injected with kynurenine became depressed (and experienced a host of neurotoxic effects). Inflammation is one effect present when kynurenine is introduced, this depletes the brain’s ability to release serotonin, which leads to depression. When the mice exercised, the depressive symptoms went away. 

FOXO3 Pathway

(Episode 672) 7:56 – FOXO3 pathway. This is a pathway activated through exercise or heat. The genes that are activated in this pathway are responsible for glutathione production, antioxidant genes, and genes responsible for repairing damage to DNA. Dr. Patrick has worked with this pathway in worms and genetically engineered the worms to always have an active FOXO3 pathway. These worms lives 50-100% longer.

(Episode 672) 9:05 – How some people can always smoke cigarets and live to over 100. If a variation of a gene occurs in more than 1% of the population, this is considered a polymorphism because it is not random and instead has been selected for due to some benefit the variation provides. There is a polymorphism in the FOXO3 where the genes are active a lot; the people who have this have a 2.7 fold increase chance of living to 100. These individuals can handle stress and DNA damage much better.


(Episode 672) 10:48 – Hormetic response. Returning to the concept of hormesis, Dr. Patrick believes that this stressing of the body in the form of heat can activate the pathways that condition the body to deal with all kinds of stress later on. Stresses such as aging and damage that comes from oxygen (reactive oxygen species as a metabolic byproduct).

High Intensity Interval Training; Long Term Potentiation

2:10 – High intensity interval training. Because you cannot get oxygen to the muscles quick enough, the cells create energy by converting glucose outside of the mitochondria and create lactate as a byproduct. This production increases the uptake of lactate in the brain. Lactate fuels norepinephrine production in the brain; norepinephrine has a role in making the connections between neurons stronger so that you can learn and remember better (known as long term potentiation).

Exercise as a Stress; Hormesis

(Episode 773) 4:37 – Exercise itself is a stress on the body, so in terms of damage exercise on its own is not good for the body. But the stress response is what is valuable. The brain prepares for the next time it will experience stress; the preparation includes activation of genes that help us deal with stress. Even something as small as breathing in oxygen opens the door to the harmful effects reactive oxygen species have on the body; the body being prepared is a potent defense and mitigates the damage.

Resistance Training; Bone Density

(Episode 773) 16:25 – A hormone known as irisin is released during resistance training and it plays a role in helping maintain bone density. Osteocalcin is also released during resistance training and is responsible for taking calcium found in the blood and moving it into bones. 30% of the US population doesn’t get enough calcium. Calcium is also used in the blood, and if there isn’t enough the body will take calcium away from the bones. Therefore it is important to keep adequate levels to ensure this balance is stable.

Omega-3s; Fat Burning

(Episode 773) 2:34:26 –  2g of EPA and 1g of DHA increased fat burning during exercise by 27% and at resting by ~14%. It has been shown that these fat compounds increased the activity of UCP1, forming new mitochondria in the fat and, as mentioned above, led to fat loss.


(Episode 901) 7:41 – Exercise and brain health. 20 minutes of aerobic exercise can increase BDNF (brain derived neurotropic factor). BDNF if a growth factor that is involved in growing new brain cells and allowing the existing brain cells to survive, combatting brain atrophy. You start to atrophy at around 20. Running has also been shown to activate the part of the brain responsible for executive function, which helps you make decisions and plan long term.


(Episode 901) 1:16:00 – Exercise shown to help depression. When inflammation occurs, the body diverts tryptophan from conversion into serotonin to the inflammatory response. Tryptophan becomes converted into kynuramine; immune cells need it to make different kinds of immune cells. Kynuramine gets converted into quinolinic acid, which is a neurotoxin that crosses the blood brain barrier; has been shown to cause depression. Where does exercise fit in? Exercise allows the muscles to absorb the kynuramine and limit the quinolinic acid production. Exercise also diverts the tryptophan towards the serotonin conversion pathway rather than the inflammatory pathways; this occurs due to the fact that exercise calls upon other branched chain amino acids to go to the body rather than the brain, which alleviates tryptophan’s competition. BDNF also plays a role in preventing depression; exercise produces this as well.

Running; Endurance

(Episode 1054) 37:56 – Exercise benefits; in particular running. Running helps Dr. Patrick with handling short term problems; running can induce a ‘daydreaming’ state where problems can be understood in a slightly different light. They discuss rumination and the negativity that rumination has been associated with; running induces this kind of thinking but with a slightly clearer head. There have been control trial showing these effects.

(Episode 1054) 40:07 – Joe discusses his experience with running. At the time of the podcast, Joe has been running up hills for about a year. First time around it was very difficult; now he runs every week. He claims that his cardio for all other activities has improved significantly; he claims to have more than doubled his endurance.

(Episode 1054) 44:33 – Dr. Patrick explains endurance. Aerobic capacity (otherwise known as VO2 max) is the capacity your body has to cary oxygen to parts of the body that need it. Once we hit age 25, our aerobic capacity decreases by 10% per decade. A study has shown that regularly doing some high intensity interval training can improve VO2 max by 12% (basically adding a decade back). The study had subjects do high intensity interval training for 24 classes over the course of 8 weeks.

Weight Lifting; Strength Training

2:50:35 – Weightlifting. Strength training has been shown to be very beneficial. Studies show that people who do strength training have a 23% lower all cause mortality and 30% lower cancer related mortality. There was another study that showed a correlation between leg strength and cognitive function (not arms; only legs). Joe explains Hindu squats.

Running; Nike

2:53:20 – Joe explains to Dr. Patrick how Nike changed the way people run by making shoes with padding on the heel rather than the ball of the foot. The ball of the foot is the natural shock absorber; running on the heel has been shown to cause knee problems. Joe runs in either Vibrum FiveFinger Shoes or Merrell Shoes. The FiveFinger shoes claim to help strengthen the feet, which is apparently true but the effects are seen after prolonged use.



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