January 6, 2020

Nutritional Biochemistry

#87 – Rick Johnson, M.D.: Metabolic Effects of Fructose

“Fructose turns out to be used by animals as a mechanism to store fat.” — Rick Johnson

Read Time 31 minutes

In this episode, Rick Johnson, professor of nephrology at the University of Colorado, explains how his research into the causes of blood pressure resulted in a change of research direction to focus more on how fructose has such profound metabolic effects. Rick begins by talking about the relationship between salt and high blood pressure, then provides a masterclass into uric acid, and then expertly reveals the mechanisms and pathways by which sugar (specifically fructose) can profoundly impact metabolic health. From there, he explains how he applies this information to real life patients as well as touches on some of the most promising ideas around pharmacotherapy that are being developed in response to the epidemics of fatty liver, insulin resistance, diabetes, and obesity. Furthermore, Rick gives his take on artificial sweeteners compared to real sugar, discusses cancer’s affinity for fructose, and much more.


We discuss:

  • The connection between blood pressure and fructose that shifted Rick’s professional focus [4:00];
  • The relationship between salt and blood pressure (and the role of sugar) [5:45];
  • Defining fructose, glucose, and sugar [19:30];
  • An ancient mutation in apes that explains why humans turn fructose into fat so easily [23:00];
  • The problems with elevated uric acid levels, and what it tells us about how sugar causes disease [31:30];
  • How sugar causes obesity—explaining the difference in glucose vs. fructose metabolism and the critical pathway induced by fructose [40:00];
  • Why drinking sugar is worse than eating it [50:00];
  • Unique ability of sugar to drive oxidative stress to the mitochondria, insulin resistance, and diabetes [54:00];
  • Why cancer loves fructose [1:00:20];
  • The many areas of the body that can use fructose [1:05:00];
  • Fructokinase inhibitors—a potential blockbuster? [1:07:15];
  • Treating high uric acid levels—Rick’s approach with patients [1:10:00];
  • Salt intake—what advice does Rick give his patients? [1:16:30];
  • How excess glucose (i.e., high carb diets) can cause problems even in the absence of fructose [1:21:00];
  • Artificial sweeteners vs. real sugar—which is better? [1:29:15];
  • Umami, MSG, alcohol, beer—do these have a role in metabolic illness? [1:33:45];
  • Fructose consumption—Is any amount acceptable? Is fruit okay? Where does Rick draw a hard line? [1:38:45]
  • How does Rick manage the sugar intake of his young kids? [1:43:00]; and
  • More.


The connection between blood pressure and fructose that shifted Rick’s professional focus [4:00]

  • It started with looking into the cause of high blood pressure
  • The running theory for years was that the kidney has a defect in its ability to excrete salt and so that you end up retaining salt and that leads to elevated blood pressure
  • Rick then figured out that when you raise uric acid in animals, they developed high blood pressure
  • So what made uric acid go up? ⇒ Sugar, and particularly fructose, raised uric acid

“We started studying fructose and pretty soon we were so excited about what we were finding that we just kind of changed our research direction to focus more on how fructose has all of its metabolic effects.”


The relationship between salt and blood pressure (and the role of sugar) [5:45]

Does salt raise blood pressure?

  • The prevailing thought is that too much salt elevates blood pressure
  • And the advice would be to restrict the amount of salt intake
  • But it isn’t really the salt amount that makes a difference, but the salt concentration
  • When you eat salt, your serum osmolality goes up
  • If you drink water in combination with eating salt, you can avoid this rise in serum osmolality and avoid the rise in blood pressure
  • Rick’s 2018 study showed that drinking water with a salty meal will prevent a rise in blood pressure

Why it would be better to have a lower blood pressure?

  • When your blood pressure is high, you have an increased risk for heart failure and stroke. 
  • As your blood pressure increases, you get a gradual increase in risk
  • But when the blood pressure gets around 160 to 180…

{end of show notes preview}

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Rick Johnson, M.D.

Rick is a professor of medicine in the Department of Nephrology at the University of Colorado since 2008 and he’s spent the last 17 years being a division chief across three very prestigious medical schools. An unbelievably prolific author, Rick has well over 700 publications in JAMA, New England Journal of Medicine, Science, et Cetera. He’s lectured across 40 countries, authored two books, including The Fat Switch, and has been funded extensively by the National Institute of Health (NIH). His primary focus in research has been on the mechanisms causing kidney disease, but it was in doing this that he became really interested in the connection between fructose (and fructose metabolism) and obesity, diabetes, heart disease, hypertension, and metabolic disease.

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.


  1. What about the effects of the pseudo sugars Dr. Johnson allows his children to have (diet sodas, splenda cakes)? Glucose intolerance has been proven to be related to changes in gut bacteria due to artificial sweetener intake!

  2. This was one of the most eye opening episodes. Listened to it 3 times. What I wanted to know was Peter’s candid thoughts on some of Dr. Johnson’s key claims. I could see uric acid having correlation with metabolic symptoms. However, if uric acid is part of the “switch”, how do we explain people that eat healthy and show no signs of metabolic symptoms but have high uric acid? Vice versa; those that have low uric acid but show metabolic symptoms. For many of us, no matter how much we exercise or eat healthy, uric acid number does not change significantly. There are several papers that suggest food has minimal effect on uric acid number.
    On the topic of Umami. Japanese people eat lots of umami infused food, but their uric acid level and diabetic cases are relatively low. More reasons I feel that food has minimal effect on uric acid level.

    Fructose —> Fat; makes sense.
    Fructose —> Uric Acid —> Fat; are we sure?

  3. I wanted to find the paper that showed serum sodium turned on the conversion of glucose to fructose. The 2013 paper linked doesn’t appear to include that. Is there another reference? This is the info from the text above.

    The role that sugar plays in hypertension

    -In the process of developing high blood pressure there are 2 players:

    There’s the initiators
    And then there’s the things that make it persistent
    The inflammation in the kidney is involved in the persistence
    In the initiation, turns out that sugar has a major role
    -Rick’s 2013 study showed that when you give a high salt diet to animals…

  4. Brilliant ‘big-brained’ conversation – I, too, have listened to it a number of times (on account of small brain), and gained so much valuable information.

    This episode with Dr. Rick Johnson, along with those with Lew Cantley and Eileen White, to which I have also listened multiple times, are truly fabulous.

    Thank you Peter.

  5. Thank you for this information Peter. I’m so glad I signed up for your emails a while ago. Seriously.

  6. Question. Lp(a), from what I understand, also supports a low oxygenated state. Is there a connection between people with very high Lp(a) and metabolic issues due to fructose?

  7. Maybe in your 2nd conversation you can more directly tie Rick Johnson’s work into Gerald Shulman’s published work.

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