#194 - How fructose drives metabolic disease | Rick Johnson, M.D.

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Feb 7, 2022

Rick Johnson, Professor of Nephrology at the University of Colorado, dives into the intriguing world of fructose metabolism and its ties to metabolic diseases. He explains how our ancestors’ survival mechanisms now pose health risks, revealing how glucose can convert to fructose. The conversation highlights the significant decline in metabolic flexibility with age, the impacts of sugar and dietary habits on our health, and strategies for preventing metabolic illnesses, including dietary modifications and innovative pharmaceutical approaches.

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INSIGHT

Fructose's Unique Metabolic Effect

Fructose uniquely causes a transient intracellular energy deficit, unlike other nutrients.
This deficit triggers a survival response, increasing hunger and fat storage.

INSIGHT

Fructose Metabolism and the Liver

The liver is the primary site of fructose metabolism and plays a key role in metabolic syndrome.
Fructokinase in the gut can metabolize small amounts of fructose, acting as a protective shield.

INSIGHT

Endogenous Fructose Production

The body can generate fructose from glucose, especially in high glucose states like diabetes.
This conversion is driven by the polyol pathway, which is induced by high glucose and uric acid.

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Episode Description:

Rick Johnson, Professor of Nephrology at the University of Colorado and a previous guest on The Drive, returns for a follow-up about unique features of fructose metabolism, and how this system that aided the survival of human ancestors has become potentially hazardous based on our culture’s dietary norms. In this episode, Rick explains how the body can generate fructose from glucose and how circulating glucose and salt levels can activate this conversion. He discusses the decline in metabolic flexibility associated with aging, as well as how factors such as sugar intake or menopause-associated hormone changes can alter responses to sugar across a lifetime. In addition, Rick lays out strategies for combating the development of metabolic illness using dietary changes and pharmaceutical therapies, and he discusses the impact of fructose metabolism and uric acid on kidney function and blood pressure. He concludes with a discussion of vasopressin, a hormone that facilitates fructose’s effects on weight gain and insulin resistance.

We discuss:

Unique features of fructose metabolism and why it matters [2:45];
A primer on fructose metabolism and uric acid [10:30];
Endogenous fructose production, the polyol pathway, and the effect of non-fructose sugars [22:00];
Findings from animal studies of glucose and fructose consumption [29:00];
What calorie-controlled studies say about the claim that a “calorie is a calorie” [42:15];
Implications for aging and disease [51:15];
Impact of endogenous fructose production on obesity and metabolic syndrome [1:01:30];
Why vulnerability to the negative effects of sugar increases with age and menopause [1:04:30];
Dietary strategies to reduce the negative impact of fructose [1:16:30];
The role of hypertension in chronic disease and tips for lowering blood pressure [1:30:45];
The impact of fructose and uric acid on kidney function and blood pressure [1:39:45];
The potential role of sodium in hypertension, obesity, and metabolic syndrome [1:49:00];
The role of vasopressin in metabolic disease [1:54:00];
More.

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