Podcast Summary
Fructose: A Significant Contributor to Health Issues: Fructose consumption can lead to high blood pressure, insulin resistance, type 2 diabetes, obesity, and elevated uric acid levels.
That fructose, a type of sugar, is a significant contributor to various health issues including high blood pressure, insulin resistance, type 2 diabetes, and obesity. Dr. Rick Johnson, a professor of medicine and nephrology, discusses his research on fructose and its effects on the body. He explains how his interest in fructose came about while studying the relationship between kidneys and high blood pressure. He discovered that elevated uric acid, which is caused by fructose consumption, can lead to high blood pressure. This finding led him to shift his research focus towards understanding the metabolic effects of fructose. It's important to note that while reducing sodium intake is still a common recommendation for managing blood pressure, recent studies have shown that other factors, such as fructose consumption, play a significant role as well.
Shifting focus from salt amount to salt concentration: Prevent acute rises in blood pressure by keeping total accumulated salt concentration low to manage high blood pressure aggressively, while being mindful of risks from extremely low blood pressure
The focus on restricting salt intake to prevent or treat high blood pressure has shifted from the amount of salt consumed to the salt concentration. When we eat salty foods, the salt concentration in our blood increases, leading to an increase in osmolality and blood pressure. This acute rise in blood pressure can be prevented by keeping the total accumulated concentration of what we ingest as low as possible. High blood pressure, even at seemingly normal levels, increases the risk for heart failure, stroke, heart attacks, and heart disease. Current guidelines recommend managing blood pressure aggressively, with 120/80 considered the optimal level. However, as we age, extremely low blood pressure can also pose risks.
Understanding Essential Hypertension's Inflammatory Cause in the Kidneys: Discovering the kidney's inflammatory response to heat shock proteins as the root cause of essential hypertension is a major breakthrough, linking it to genetic polymorphisms. Exercise, despite inducing heat shock proteins, is beneficial due to its effects on mitochondrial function and blood vessel dilation.
Essential hypertension, or high blood pressure with no clear cause, may be driven by an inflammatory response in the kidneys. This response, which can be triggered by various factors including external stimuli or an autoimmune reaction to heat shock proteins, leads to reduced blood flow and tissue damage in the kidney. This injury, in turn, causes the kidneys to retain sodium, leading to high serum sodium levels and increased blood pressure. The discovery of this mechanism is a major breakthrough in understanding the cause of primary hypertension, and it's linked to many genetic polymorphisms. However, it doesn't mean that exercise, which induces heat shock proteins, paradoxically increases hypertension. Instead, exercise is beneficial for improving mitochondrial function and blood vessel dilation.
High salt diet increases fructose production, leading to higher blood pressure: A high salt diet can increase fructose production, leading to higher blood pressure. Exercise improves kidney function and releases heat shock proteins, benefiting overall health.
A high salt diet can lead to an increase in blood pressure through the conversion of glucose to fructose in the body. Exercise, on the other hand, improves kidney function and releases heat shock proteins, which have numerous health benefits. It's important to note that glucose and fructose are different types of sugars. Glucose is the primary energy fuel used by the body and is stored as glycogen, while fructose is involved in energy storage and triggers changes that favor energy storage. A high salt diet can increase the production of fructose in the body, leading to an increase in blood pressure. It's crucial to be aware of the distinction between these two types of sugars and the effects they have on the body.
Mutation allowing early apes to store more fat through efficient fructose metabolism: A 12-15 million year old mutation enabled early apes to store more fat by metabolizing fructose more efficiently, enhancing their survival during food scarcity
A mutation that occurred around 12-15 million years ago allowed some early apes to store more fat by metabolizing fructose more efficiently, which became a crucial survival mechanism during periods of food scarcity. This mutation, which affected uric acid metabolism, made the apes more responsive to the uric acid produced when fructose is metabolized, enabling them to store more fat and survive longer during winter seasons. This discovery provides insight into the evolutionary significance of fructose metabolism and its impact on the survival of early primates.
Uricase mutation in early humans: An evolutionary advantage led to a mutation that made early humans more efficient at processing fructose but increased susceptibility to gout
An extinct European ape carried a mutation that made it more efficient at turning fructose into fat, allowing it to survive and eventually become the common ancestor of humans and other great apes. This mutation, known as the uricase mutation, also made humans more sensitive to sugar and prone to gout. Uric acid is a byproduct of the breakdown of DNA and RNA, and diets high in protein, particularly from sources rich in nucleic acids, can increase uric acid levels and the risk of gout. The mutation likely occurred during a critical period when these apes migrated from Africa to Europe and then back to Africa and Asia. The uricase mutation is unique to humans and other primates, and it has been suggested that it may have provided a survival advantage during human evolution.
Uric acid's impact on health goes beyond gout: Uric acid levels linked to high blood pressure, insulin resistance, and metabolic issues, influenced by estrogen and sugar consumption.
Uric acid levels are connected to various health issues beyond just gout. Uric acid levels can be influenced by estrogen in women and go up due to sugar consumption. High uric acid levels have been linked to high blood pressure, and studies have shown that raising uric acid in animals leads to hypertension, insulin resistance, and other metabolic issues. The mechanism behind this involves the unique way uric acid is generated from fructose metabolism, which plays a role in how sugar causes disease. Initially, this idea was met with skepticism, but research has since confirmed its validity.
Fructose Metabolism Leads to ATP Depletion and Uric Acid Production: Fructose metabolism results in ATP depletion and uric acid production, contributing to obesity, insulin resistance, fatty liver, and high blood pressure.
While fructose and glucose are similar in appearance, their metabolic processes lead to vastly different outcomes. Unlike glucose, which results in an increase in cellular energy (ATP), fructose metabolism can cause a significant drop in ATP levels due to an unregulated consumption of ATP. This ATP depletion triggers a cascade of reactions, including the activation of an enzyme called AMP diaminase, which converts AMP to uric acid. This process is linked to the development of obesity, insulin resistance, fatty liver, and high blood pressure. Essentially, fructose acts as a mechanism for animals to store fat, particularly when they want to gain weight. This is distinct from the uricase mutation, which also contributes to obesity but through a different mechanism.
AMP encounters a decision point leading to energy burning or fat storage: AMP's choice between energy burning and fat storage depends on intracellular phosphate levels, impacting metabolic effects and potentially diabetes outcome.
A molecule of adenosine monophosphate (AMP) encounters a crucial decision point in the cell, which can lead it down either the AMP-activated protein kinase (AMPK) pathway or the adenosine monophosphate deaminase (AMPD) pathway. The choice between these two pathways is determined by the intracellular phosphate level, which falls due to the phosphorylation of fructose by ATP. If AMP goes down the AMPK pathway, it results in energy burning and fat usage, with positive effects such as treating diabetes. In contrast, if it goes down the AMPD pathway, it leads to fat storage and insulin resistance, potentially resulting in diabetes. This switch is critical in various species, including humans and hibernating squirrels, which can toggle between AMPK and AMPD to gain or lose weight. The uric acid generated during the AMPD pathway plays a role in these biological effects. Interestingly, the speed and concentration of fructose intake also impact the metabolic effects, with rapid absorption and high concentrations leading to more significant metabolic changes.
Fructose Consumption and Metabolic Syndrome: Fructose consumption can lead to metabolic syndrome through increased uric acid, oxidative stress, decreased mitochondrial function, elevated glucose levels, high blood pressure, increased fat storage, elevated triglycerides, and decreased HDL cholesterol levels. These effects can occur without significant weight gain.
Consuming large amounts of fructose can contribute to the development of metabolic syndrome. The body processes fructose differently than other sugars, leading to increased uric acid production, oxidative stress in the mitochondria, and decreased mitochondrial function. These effects can result in elevated glucose levels, high blood pressure, increased fat storage, and elevated triglycerides – all key characteristics of metabolic syndrome. Additionally, fructose can also lower HDL cholesterol levels. The oxidative stress caused by fructose inhibits an enzyme that drives fat oxidation, leading to increased fat synthesis and fatty liver. The development of insulin resistance and damage to the pancreatic islets further exacerbates the situation. These effects can occur even without significant weight gain.
Fructose: From Survival Tool to Health Hazard: Excessive fructose consumption can lead to insulin resistance, inflammation, increased triglycerides, and decreased HDL cholesterol, negatively impacting health, especially in the context of cancer cells.
Fructose, a simple sugar, has played a significant role in survival for many species throughout evolution, but its overconsumption can lead to detrimental health effects. Fructose is linked to insulin resistance, which can contribute to islet cell dysfunction and type 2 diabetes through a low-grade inflammation process. Additionally, a high consumption of fructose can lead to an increase in triglycerides and a decrease in HDL cholesterol. Fructose was an essential survival tool for animals in low oxygen environments and during periods of near starvation, as it allowed them to store water, energy, and become insulin resistant. However, in modern times, excessive fructose consumption can negatively impact health, particularly in the context of cancer cells, which thrive in low oxygen states and prefer fructose as their fuel source.
Fructose Metabolism and Cancer Growth: Fructose metabolism in organs other than the liver, particularly the intestine, can contribute to cancer growth. Inhibiting the enzyme fructose kinase can hinder cancer progression, specifically in colon cancer.
Fructose, a common sugar found in many foods and beverages, plays a more significant role in the body than previously thought. It's not just metabolized in the liver but also in other organs like the intestine, where it can contribute to cancer growth. Blocking the enzyme fructose kinase, which is responsible for metabolizing fructose, can inhibit cancer growth in colon cancer, for instance, by up to 50%. The body's metabolism shifts from a mitochondrial-based metabolism to a glycolytic one when fructose is present, leading to increased lactate levels. Fructose is also found in the brain, where it may be involved in disorders like Alzheimer's disease. People with a rare condition called fructose intolerance are born without active fructokinase, the enzyme responsible for metabolizing fructose, and they don't develop obesity, diabetes, or insulin resistance. Fructose kinase is an evolutionary survival enzyme, but in today's world, its presence may contribute to health issues. Researchers are developing fructose kinase inhibitors, such as Pfizer's drug in phase three trials, which could potentially treat conditions like fatty liver and cancer.
Doctors have been using allopurinol since 2002 to lower uric acid levels in patients, even before the onset of gout.: Doctors use allopurinol to lower uric acid levels, benefiting insulin resistance, kidney disease, hypertension, and blood pressure control. Target uric acid level: 5.5 mg/dL or higher.
While there is ongoing research into fructose kinase inhibitors as a potential solution for those seeking to consume more sugar without the negative consequences, in the clinical practice, doctors like Dr. Avram have been using allopurinol since 2002 to lower uric acid levels in patients, even before the onset of gout. Allopurinol is not without risks, including allergic reactions, especially in Asians, and the need for careful consideration of benefits versus risks. However, the data suggests that lowering uric acid could benefit insulin resistance, kidney disease, hypertension, and blood pressure control. The target uric acid level for intervention is 5.5 mg/dL or higher, as risks increase at this level, although most labs do not flag it until it reaches 6.5 mg/dL. Allopurinol is the most effective way to reduce intracellular uric acid, making it a preferred option over other uric acid-lowering drugs. While the risk of Stevens-Johnson syndrome is the primary concern with allopurinol, other potential risks include mild rashes, liver function test elevations, and increased xanthine levels in the urine, although these are rare.
Maintaining balance of salt and water intake is key for managing kidney disease: Balancing salt and water intake, along with adequate water consumption, can potentially slow the progression of kidney disease. Individual needs may vary, so consult healthcare professionals for personalized recommendations.
While sodium restriction is important for managing kidney disease, the focus should be on the balance of salt and water intake. Contrary to popular belief, it's not just about reducing salt consumption, but also ensuring adequate water intake. This is because the body produces fructose when salt is consumed without enough water, which can lead to negative health effects, including obesity and diabetes. Interestingly, animals, such as whales, use fructose to make fat as a means for preserving water. Therefore, drinking water can help suppress some of the harmful effects of fructose. For patients with chronic kidney disease, maintaining a balance of salt and water intake, along with adequate water consumption, can potentially slow the progression of kidney disease. However, it's important to note that individual needs may vary, and healthcare professionals should provide personalized recommendations based on each patient's unique situation.
Maintaining health through adequate water intake and limiting fructose consumption: Avoiding added sugars and focusing on overall carb reduction can help prevent health issues linked to fructose production within the body, including kidney disease and fatty liver disease.
Focusing on adequate water intake and limiting fructose consumption can help prevent or manage various health issues, including kidney disease and fatty liver disease. However, it's important to note that our bodies can produce fructose from other sources like high salt diets, dehydration, or high uric acid levels. Even if we avoid added sugars, we might still be producing fructose within our bodies. Therefore, reducing overall carbohydrate intake, especially high glycemic carbs, can be beneficial in preventing the induction of the enzyme that converts glucose to fructose. This can help maintain healthy liver function and insulin sensitivity.
Fructose Reduction Isn't Always the Answer: Fructose can lead to health issues even without weight gain, and controlling energy intake doesn't eliminate its impact. The industry's argument oversimplifies the issue, and artificial sweeteners may not be the healthier alternative.
While fructose reduction can bring benefits, it's important to consider that the body may produce significant amounts of fructose from glucose if the enzyme aldose reductase has been triggered. The issue may not solely be about total energy intake, but rather the specific carbohydrate. Pair feeding studies, which control food intake, have shown that even without weight gain, fructose can still lead to fatty liver, insulin resistance, and other health issues. The sugar industry's argument that a calorie is a calorie and controlling energy intake eliminates the impact of fructose is flawed because in real life, individuals don't have a clamp on their response to food. Additionally, artificial sweeteners may not be the healthier alternative some believe, as animals still develop metabolic syndrome even when their sweet taste buds are knocked out.
Sweet Preferences Affect Metabolism Beyond Taste: Real sugar stimulates dopamine and affects metabolism, while long-term safety of artificial sweeteners and additives is uncertain
Our preference for sweet foods isn't just limited to our taste buds and brain, but also extends to our periphery where metabolism occurs. Real sugar, unlike artificial sweeteners, stimulates dopamine and other effects independently of the sweet taste. While there is evidence that artificial sugars are safer than sugar for weight gain in animals, their long-term safety in humans is not fully known. The same goes for additives like aspartame and sucralose. Umami, the savory taste, is driven by glutamate and enhanced by purines. Umami-rich foods, such as shrimp and Caesar salad, are often loved by people, but if they contain high levels of purines, they may raise uric acid and potentially contribute to weight gain or other health risks. Overall, it's important to consider the lesser of two evils when it comes to sugar and artificial sweeteners, but more research is needed to fully understand their long-term effects on human health.
Considering the Role of Umami and Fructose in Metabolic Health: While reducing sugar, high glycemic carbs, and salt is important for metabolic health, be aware of umami-rich foods and beverages, especially those high in fructose. Moderate consumption of whole fruits and some processed foods is generally safe, but limit large quantities of fructose from juices, sodas, and sports drinks.
While reducing intake of sugar, high glycemic carbs, and salty foods is essential for metabolic health, it's also crucial to consider the role of umami-containing foods and beverages, particularly those high in fructose. Foods like shrimp, high-umami processed foods, and beverages like beer can activate metabolic pathways contributing to metabolic disease. Regarding fructose, consuming it in moderation, especially in the form of whole fruits, is generally safe and may not hinder the benefits of a low-fructose diet. However, large quantities of fructose from sources like fruit juices, sodas, and sports drinks should be avoided. Ultimately, maintaining a balanced diet and being mindful of portion sizes and frequency of consumption is key to promoting metabolic health.
Fruit and Sugar: Balancing Health Benefits and Risks: Limit fruit intake for those with non-alcoholic fatty liver disease to 10g fructose/day. Teach kids about sugar, read labels, and choose whole fruits over dried or sugary drinks.
While fruits have health benefits, they also contain significant amounts of sugar, particularly fructose. Consuming large quantities of fruit at once can impair fat oxidation and lead to weight gain. It's recommended to limit fruit intake for those with non-alcoholic fatty liver disease to 10 grams of fructose per day in the form of whole fruit. Parents can teach their children about sugar and its health effects while still allowing for occasional treats. Educating children about the importance of sugar in their diets and teaching them to read food labels can help them make informed choices. The carbonation in soft drinks may make it easier to consume large amounts of sugar, and dried fruit, while high in nutrients when fresh, loses many of these benefits when dried and becomes a source of concentrated fructose.
Understanding the Impact of Seemingly Harmless Foods: Dr. Rick Johnson's research on fructose highlights the importance of context when evaluating the impact of trail mix and sports drinks. His approach focuses on lab work and offers access to exclusive content through a membership program.
Context is crucial when it comes to evaluating the impact of seemingly harmless foods like trail mix and sports drinks. While these items may have specific uses in certain situations, such as mountaineering or professional athletics, the majority of consumption occurs outside of these contexts. Dr. Rick Johnson's research on the harmful effects of fructose provides a strong scientific foundation, and his approach has focused on the lab work rather than advocacy or policy. Listeners are encouraged to learn more about his work and consider becoming members for access to exclusive content. The membership program offers comprehensive podcast show notes, monthly AMA episodes, a private podcast feed, short podcast clips, discounts on recommended products, and more. Remember, this podcast is for general informational purposes only and does not constitute medical advice. Always consult a healthcare professional for any medical concerns. Conflicts of interest are disclosed on Dr. Atia's website.
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