Podcast Summary
Discovering the link between high uric acid levels and hypertension through research on fructose metabolism: Renowned professor Dr. Rick Johnson's research on fructose metabolism led to the discovery of the link between high uric acid levels and hypertension, highlighting the complex relationship between diet, health, and disease.
Dr. Rick Johnson, a renowned professor of medicine and expert on fructose metabolism, has spent his career researching the mechanisms of kidney disease and the connection to obesity, diabetes, and heart disease. His work on fructose led him to discover the link between high uric acid levels and hypertension. Dr. Johnson's groundbreaking research has been published in top medical journals and funded by the NIH. In this podcast episode, they discuss the controversial relationship between salt and high blood pressure, the evolution of an enzyme that allows us to use fructose, and the potential of pharmacotherapy in response to metabolic diseases caused by sugar. Dr. Johnson's expertise in fructose and its health implications is a testament to the complex relationship between diet, health, and disease.
Focus on sodium concentration for managing blood pressure: Consider the sodium concentration, or osmolality, when managing blood pressure, not just the amount consumed, to maintain stable serum sodium levels and reduce negative health consequences.
The focus on reducing sodium intake for managing blood pressure has evolved. While sodium restriction was once a primary recommendation, current research suggests that the salt concentration, or osmolality, plays a more significant role in acutely raising blood pressure. When we consume salty foods, our serum sodium levels increase, causing a rise in osmolality and subsequent increase in blood pressure. This transient rise in blood pressure can lead to negative health consequences, such as increased risk for heart failure, stroke, and heart disease. Therefore, it's essential to consider not just the amount of salt consumed but also the concentration, and aim for maintaining a stable serum sodium level.
Inflammatory response in kidneys may cause essential hypertension: Recent research suggests an inflammatory response in the kidneys, possibly an autoimmune reaction to heat shock proteins, may cause essential hypertension by reducing blood flow, causing tissue damage, and leading to increased sodium retention and high blood pressure.
Essential hypertension, or high blood pressure without an obvious cause, may be linked to an inflammatory response in the kidneys. This response, driven by T cells and macrophages, causes a constriction of blood vessels and leads to reduced blood flow and tissue damage. The injury resulting from this ischemia can cause the kidneys to retain sodium, leading to high serum sodium levels and increased blood pressure. Recent research suggests that this inflammatory reaction may be an autoimmune response to heat shock proteins, which are involved in protein clearance and system maintenance. This mechanism may be a significant contributor to the cause of primary hypertension, although its prevalence is not yet clear.
Understanding the Complex Factors of Hypertension: Exercise benefits hypertension by improving mitochondrial function, dilating blood vessels, and enhancing kidney function, while limiting salt intake and reducing fructose consumption can help prevent or manage hypertension.
Hypertension, or high blood pressure, is a complex condition influenced by various factors including genetics, immune response, salt intake, and sugar metabolism. Exercise is beneficial for improving mitochondrial function, dilating blood vessels, and kidney function, despite the release of heat shock proteins. Salt intake can increase blood pressure acutely by activating an enzyme that converts glucose to fructose, which in turn raises blood pressure. Sugar, particularly fructose, plays a role in the initiation and persistence of hypertension by favoring energy storage and inflammation in the kidneys. Glucose is the primary energy fuel used by the body, while fructose is involved in energy storage. Fructose is sweeter than glucose and is found in fruits and honey. The body stores excess fructose as fat.
Ancient ape adaptation to fruit metabolism: Around 12-15 million years ago, an adaptation allowing ancient apes to effectively metabolize and store fructose for fat production during food scarcity occurred, involving a change in uric acid metabolism.
Around 12-15 million years ago, a mutation occurred in our ancient ape ancestors that allowed them to effectively metabolize and store fructose from fruit for fat production, which was crucial for their survival during periods of food scarcity. This mutation involved a change in uric acid metabolism, enabling them to better process the uric acid produced when fructose is metabolized. This adaptation was particularly important during the Miocene period when global cooling led to the loss of fruit sources in Europe, causing many ape species to go extinct. However, in Africa, where fruit trees continued to thrive year-round, this mutation helped our ancestors maintain their ability to survive and eventually evolve into modern humans.
An ancient mutation linked to human evolution and health: An efficiency in converting fructose to fat and producing high uric acid levels, derived from a European uricase mutation, benefited our ancestors but increased susceptibility to gout
An ancient mutation in our human ancestors allowed them to efficiently convert fructose into fat while producing high levels of uric acid. This mutation, known as the European uricase mutation, occurred in apes that migrated from Africa to Europe during a period of climate change. When these apes returned to Africa and Asia, they became the ancestors of modern humans and great apes. Although this mutation provided a survival advantage, it also made humans more prone to gout due to their high uric acid levels. The mutation allows humans to convert purines, found in DNA and RNA of protein-rich foods, into uric acid more efficiently than other animals. This mutation's impact on human evolution and health is a fascinating example of how genetic adaptations can have both benefits and drawbacks.
Uric acid's role in gout and health: Uric acid, a component in beer and linked to gout, also influences blood pressure and metabolic syndrome. Men generally have higher levels than women, except post-menopause, due to estrogen's role in uric acid excretion.
Uric acid, a component found in beer and precipitator of gout, is influenced by various factors including diet, sex, and estrogen levels. Historically, gout was linked to the consumption of rich foods, alcohol, and sugar. Uric acid is also connected to high blood pressure and metabolic syndrome, as seen in studies using uricase inhibitors and fructose. The mechanism involves uric acid's role in sugar metabolism. Uric acid levels are generally higher in men than women, except after menopause, due to estrogen's role in uric acid excretion. The discovery of uric acid's role in blood pressure and metabolic syndrome was a significant finding, as it led to the development of treatments targeting uric acid to improve these conditions.
Fructose Metabolism Differences from Glucose: Fructose metabolism causes a significant drop in cellular energy (ATP), leading to energy conservation, increased fat storage, and potential health issues like obesity, insulin resistance, fatty liver, and high blood pressure.
The metabolism of fructose is fundamentally different from that of glucose. While both nutrients are converted into energy, the process of metabolizing fructose results in a significant drop in cellular energy (ATP) levels. Unlike glucose metabolism, which is regulated to prevent excessive ATP depletion, fructose metabolism can cause a substantial drop in ATP, leading the body to conserve energy by reducing metabolism, increasing fat storage, and triggering hunger and thirst. This unregulated ATP depletion also activates a cascade of reactions, including the production of uric acid, which contributes to various health issues such as obesity, insulin resistance, fatty liver, and high blood pressure.
The Fate of ADP: Burn Energy or Store Fat?: Our bodies decide whether to burn energy or store fat based on the intracellular phosphate levels and the pathway of ADP. Rapid fructose consumption can influence this decision and lead to significant metabolic changes.
Our bodies produce energy through the process of ATP becoming ADP, releasing a phosphate for energy use. However, the fate of the resulting ADP hinges on a critical decision point: it can either follow the AMP-K pathway, which burns energy and promotes fat loss, or the AMP-D pathway, which leads to fat storage and potential insulin resistance. This choice is influenced by intracellular phosphate levels, which drop when ATP is taken up by processes like fructose metabolism. This discovery, unique to species capable of gaining weight, has significant implications for understanding metabolic processes and potential treatments for conditions like diabetes. Interestingly, the speed and concentration of fructose intake can influence the metabolic effects, with rapid consumption leading to more significant metabolic changes.
Fructose absorption speed impacts metabolic health: Rapid fructose absorption leads to increased triglycerides, uric acid, and blood pressure, contributing to metabolic syndrome and insulin resistance.
The speed of fructose absorption plays a crucial role in its negative metabolic effects. If fructose is consumed quickly, such as in the form of sugary drinks, it can lead to rapid increases in triglycerides, uric acid, and blood pressure, contributing to metabolic syndrome. This occurs due to the inhibition of fat oxidation and the stimulation of fat synthesis in the mitochondria, resulting in fatty liver and insulin resistance. Additionally, uric acid generated from fructose can cause oxidative stress in the mitochondria and pancreatic islets, further exacerbating these conditions. Consuming large amounts of fructose, even without weight gain, can lead to the development of metabolic syndrome and diabetes.
Fructose's Initial Role in Survival and Its Detrimental Effects: Fructose initially helps animals survive in harsh conditions by increasing insulin resistance and storing energy, but prolonged exposure can lead to insulin resistance, islet cell dysfunction, metabolic diseases, oxidative stress, and lower HDL cholesterol.
Fructose, a simple sugar, plays a complex role in metabolism. Initially, it helps animals survive in low food and oxygen environments by increasing insulin resistance and storing energy. However, prolonged exposure to fructose can lead to insulin resistance, islet cell dysfunction, and metabolic diseases like diabetes and fatty liver disease. The body responds to fructose by increasing uric acid transport proteins, leading to oxidative stress and a drop in insulin production. Additionally, fructose can lower HDL cholesterol, but the mechanism is not well understood. Despite its role in survival, excessive fructose consumption can have detrimental effects on health.
Fructose metabolism in cancer cells: Fructose is a preferred fuel source for certain cancer cells, especially in low oxygen environments. Blocking fructose metabolism can inhibit cancer growth by up to 50%.
Fructose plays a significant role in the metabolism of certain types of cancer cells, particularly those in the colon, liver, kidney, breasts, brain, and intestines. These cancer cells preferentially use fructose as their fuel source, especially in low oxygen environments. Blocking the fructose metabolism pathway, specifically fructose kinase, can inhibit cancer growth by up to 50%. This shift from mitochondrial-based metabolism to glycolytic metabolism results in high lactate levels. Contrary to popular belief, fructose is not solely metabolized in the liver but also in the intestine, kidneys, brain, and other tissues. The discovery of fructose kinase in various organs, including the heart, raises the possibility of its involvement in more conditions than previously thought. For instance, it may be linked to insulin resistance and Alzheimer's disease. People with a rare condition called fructose intolerance, who lack active fructokinase, can consume large amounts of sugar without experiencing negative health effects, such as weight gain, insulin resistance, or high uric acid levels. This enzyme is considered a survival mechanism for times of food scarcity. While there are potential benefits to having fructose kinase, its inhibition could contribute to addressing various health issues in the modern world.
New drug for fatty liver and metabolic syndrome in trials, Older drug Allopurinol still used despite risks: A new drug inhibiting fructose kinase shows promise for treating fatty liver and preventing metabolic syndrome, while Allopurinol, an older drug used to lower uric acid, remains in use due to potential benefits despite risks.
Pfizer's new drug in phase three trials, which inhibits fructose kinase, shows promise in treating fatty liver and potentially preventing sugar-induced metabolic syndrome. However, its market size may depend on whether it's used primarily for treating active conditions or for those seeking to consume more sugar without consequences. Allopurinol, an older drug used to lower uric acid, remains in clinical practice, despite its potential risks. Doctors, like the speaker, still use it to treat patients with high uric acid levels, even before the development of gout, due to its potential benefits in preventing insulin resistance, hypertension, and kidney disease. The target uric acid level for treatment is 5.5 mg/dL or higher, as risks increase significantly above this level. Allopurinol's main risk is Stevens-Johnson syndrome, but other potential risks include mild rashes and elevated liver function tests. Alternatives to allopurinol, such as febuxostat and probenecid, also exist for lowering uric acid levels.
Managing Uric Acid Levels: Balancing Salt and Xanthinoxidase Inhibitors: Balancing salt intake and maintaining water consumption while considering xanthinoxidase inhibitors like alopurinol and febuxostat for managing uric acid levels and associated health risks.
When it comes to managing uric acid levels and associated health risks, inhibitors of xanthinoxidase, such as alopurinol and febuxostat, are effective in reducing intracellular uric acid. However, febuxostat may not be as cardiovascular risk-reducing as alopurinol, and it's more expensive. Regarding sodium intake, it's not just about the amount but the balance of salt and water. Consuming salt with water can help mitigate the negative effects, as the rise in salt triggers the production of fructose, which can contribute to obesity, diabetes, and other health issues. So, encouraging patients to drink plenty of water and limit their salt intake, but maintain the balance, is key.
Staying hydrated and limiting fructose intake can have health benefits: Hydration and limiting fructose intake can slow kidney disease progression, suppress metabolic syndrome effects, and help suppress fructose production in the liver. Drinking water or zero osmolarity beverages can aid in this process.
Staying hydrated and limiting fructose intake can have significant health benefits, including slowing the progression of kidney disease and suppressing some effects of metabolic syndrome. Animals, including humans, produce water when they burn fat produced from fructose, a process called metabolic water. This discovery explains the old wives' tale about drinking water to stay skinny. Water, or any zero osmolarity beverage, can help suppress the effects of fructose. However, avoiding fructose is easier said than done since it's prevalent in many processed and packaged foods. Our bodies can also produce fructose from high salt diets, dehydration, high uric acid levels, and high glycemic diets. Even glucose, which doesn't contain fructose, can induce the production of fructose in the liver. This discovery suggests that a diet high in excess carbohydrates, even without added sugar, could lead to fatty liver disease if the liver's fructose-producing enzyme is activated. For young people, the enforcing of fructose restriction and maintaining low uric acid levels could potentially reverse the induction of this enzyme.
Fructose consumption contributes to health issues: Consuming large amounts of fructose, especially without adequate insulin, can lead to metabolic syndrome, fatty liver, and other health issues due to unique metabolism in the liver.
Consuming large amounts of fructose, particularly in the absence of adequate insulin function, can contribute to metabolic syndrome, fatty liver, and other health issues. This is because fructose is metabolized differently than other sugars, leading to the production of harmful substances in the liver. The issue is not just about total energy intake, but specifically about the consumption of fructose. Pair feeding studies have shown that even when animals are given the same amount of food, those consuming fructose still experience these health issues. The sugar industry's argument that a calorie is a calorie and that artificial sweeteners are a better alternative is not entirely accurate, as artificial sweeteners can still have negative effects, including disruptions to the gut microbiome and potential negative impacts on metabolism.
The metabolism of sugar affects our preference for real sugar over artificial alternatives: Sugar's metabolism stimulates dopamine and other effects, making real sugar more appealing than artificial alternatives, despite their similar sweet taste.
Our affinity for sugar goes beyond our taste buds and brain, as metabolism plays a role in our preference for real sugar over artificial alternatives. The metabolism of sugar stimulates dopamine and other effects independently of the sweet taste, whereas artificial sugars only activate the sweet taste. However, the safety of artificial sweeteners like aspartame and sucralose is still a topic of debate. Umami, the savory taste, is driven by glutamate and enhanced by purines, and is linked to obesity in some studies. MSG is the primary stimulant of umami, but its safety is also a subject of controversy. Overall, while much focus is on the central effects of food on our brain, it's important to consider the peripheral effects in our metabolism as well.
Umai-rich foods and fructose: Balance is key: Excessive umami foods, especially high-purine ones, may raise uric acid and contribute to metabolic diseases. Moderate fruit consumption is fine, but limit fructose-laden beverages.
While umami-rich foods, which activate the umami pathway, are generally loved, excessive consumption of these foods, especially those high in purines, may contribute to metabolic diseases by raising uric acid levels. Foods to be cautious about include shrimp, beer, and high-sodium snacks like potato chips. Regarding fructose, it's best to avoid liquids containing fructose, but natural fruit consumption in moderation does not seem to hinder the benefits of a low-fructose diet. However, individual consumption habits and portion sizes should be taken into account. The dos and don'ts of healthy eating can be complex, and it's important to remember that the dose, speed of delivery, and combination of foods can significantly impact their effects on the body.
Excessive fructose intake can impair fat oxidation and contribute to weight gain: Limit fructose intake to 10 grams per day for those with non-alcoholic fatty liver disease, read food labels, and encourage healthy habits to avoid excessive sugar consumption, especially from soft drinks.
While fruits have numerous health benefits, consuming large quantities of them at once can lead to negative effects, particularly when it comes to fructose intake. The body can handle smaller amounts of fructose found in whole fruits, but excessive consumption can impair fat oxidation and contribute to weight gain. A recommended limit for patients with non-alcoholic fatty liver disease is 10 grams of fructose per day. Parents can balance the knowledge of sugar's health effects with their children's desires by being open about the reasons for restrictions and encouraging healthy habits. Children can be taught to read food labels and understand the importance of limiting sugar intake from an early age. The carbonation in soft drinks can mask the taste of sugar, making it easier to consume larger quantities unknowingly.
Soft drinks and dried fruit: Surprising snacks for kids: Soft drinks might make sugar consumption easier for kids due to carbonation, while dried fruit loses many nutrients during drying. Rick's research on fructose harms provides valuable insights, but context matters with trail mix and sports drinks.
While teaching kids with soft drinks can be effective, the carbonation in these drinks might make it easier for children to consume large amounts of sugar. The phosphoric acid in soft drinks could also contribute to their palatability. Dried fruit, although natural, can be disappointing as a healthy snack since many of its nutrients are lost during the drying process. Trail mix and sports drinks are often consumed in non-optimal contexts, and their overall health impact depends on the individual's energy requirements and activity level. Rick's research on the harm of fructose provides a strong scientific foundation, and his approach to the issue is unique as he focuses on the science rather than policy or advocacy. For those interested in more in-depth content, consider joining the membership program at peteratiamd.com/subscribe for exclusive podcast show notes, monthly AMA episodes, access to a private podcast feed, discounts on recommended products, and more. Remember, this podcast is for informational purposes only and should not replace professional medical advice.
