The following was summarized and transcribed from a lecture of Dr. Robert Lustig. Dr. Lustig is an Emeritus Professor of Pediatrics in the Division of Endocrinology and a Member of the Institute for Health Policy Studies at UCSF. Dr. Lustig is a neuroendocrinologist with expertise in metabolism, obesity, and cellular nutrition.
He is one of the leaders of the current “anti-sugar” movement that is changing the food industry. He has dedicated his retirement from clinical medicine to help fix the food supply in any way he can, to reduce human suffering, and to salvage the environment. Dr. Lustig graduated from MIT in 1976 and received his M.D. from Cornell University Medical College in 1980. He also received his Masters of Studies in Law (MSL) degree at the University of California, Hastings College of the Law in 2013.
He is the author of the popular books Fat Chance (2012), The Hacking of the American Mind (2017), and Metabolical: The Lure and the Lies of Processed Food, Nutrition, and Modern Medicine (2021). He is the Chief Science Officer of the non-profit Eat REAL, he is on the Advisory Boards of the UC Davis Innovation Institute for Food and Health, the Center for Humane Technology, Simplex Health, Levels Health, and ReadOut Health, and he is the Chief Medical Officer of BioLumen Technologies, Foogal, Perfact, and Kalin Health.
None of the above "hateful eight" foundational pathologies have any effective medications, except for individualized dietary, lifestyle and biochemical changes.
Individualized diet, supplement and analysis of your body, lifestyle and subsequent biochemistry is the only solution that actually works.
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Here they are:
- Glycation: which is the process of sugar molecules attaching to proteins, is primarily caused by consuming carbohydrates and fructose while lacking fiber in the diet.
- Oxidative Stress: which is an imbalance of free radicals and antioxidants, is driven by consuming glucose and fructose.
- Mitochondrial Dysfunction: which affects the energy production in cells, is primarily caused by consuming fructose. Omega-6 fatty acids, which are unhealthy fats, and a lack of essential micronutrients contribute to various health issues.
- Insulin Resistance: a condition where cells fail to respond to insulin properly, is driven by consuming fructose and branched-chain amino acids like leucine, isoleucine, and valine.
- Membrane Instability: is caused by a lack of Omega-3 fatty acids, which are essential for cell function.
- Inflammation: can be attributed to consuming carbon and gluten. Carbohydrates and gluten, along with certain omega-6 fatty acids, contribute to inflammation.
- Epigenetics/Methylation: is hindered by a deficiency in folic acid and vitamin B12.
- Autophagy: allows your body to break down and reuse old cell parts so your cells can operate more efficiently.
The main idea here is that none of these Pathways can be targeted with drugs, except perhaps inflammation, which is still uncertain depending on the specific inflammation. However, the good news is that all eight of these Pathways can be influenced and improved through the use of food.
All of them have a common characteristic, and it's not just their mouthwatering taste. The reason behind their deliciousness is that they are not your ordinary coffees; they are rich and full-bodied. Every single one of them boasts a beautiful brown hue, connecting them in their appearance.
As an example of "browning foods" we have baked chicken, broasted beef, coffee, bread, beer.
What do all these foods and drinks have in common? They're all brown-colored. The common link here is the glycation reaction -- the binding of the glucose to an epsilon amino group of amino acid lysine. The way to think about this is "you can roast your meat at 375 degrees for 1 hour, or for 75 years." The answer is the same: you are browning it. You sitting on your chair right now are browning and your mitochondria "brown" routinely as a natural part of the metabolic process. If you had orange juice before breakfast you are browning 7 times faster.
Why is that?
In one word: glycation. Glucose exhibits an aldehyde group at position one in its linear form, which combines with an Epsilon amino group of Lysine at position one on the hemoglobin molecule. This interaction leads to the formation of a shift base, which undergoes spontaneous decomposition, resulting in the formation of a covalent linkage. This fascinating process is known as the amidori rearrangement.
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Now, let's explore the reason behind this phenomenon. It all comes down to:
1. Glycation
Take a look at glucose - you'll notice that it has an aldehyde group on the first position of its linear form. This aldehyde group combines with an Epsilon amino group of Lysine at the first position on the hemoglobin molecule. This combination forms a shift base, which then spontaneously decomposes to form a covalent linkage. This process is known as the amidori rearrangement. This is what we refer to as hemoglobin A1c, which is used to measure the blood glucose levels in diabetics. It correlates with the degree of blood glucose elevation, which is quite significant.
Interestingly, fructose, the sweet molecule found in refined sugar, undergoes this reaction seven times faster than glucose.
2. Oxidative Stress
Every time my body undergoes a reaction, it releases a small amount of hydrogen peroxide and oxygen radicals. These oxygen radicals need to be neutralized by antioxidants, otherwise they can cause damage such as lipid peroxidation or protein denaturation. This process is known as oxidative stress, which is similar to how nails rust due to iron oxide. However, in our case, it's carbonyls that cause the rusting effect. These reactive oxygen species, particularly superoxides, are the culprits behind the problem. This oxidative stress occurs not only in carbohydrates but also in fats, leading to the formation of acrylamide when carbohydrates and fats are heated together, like in the case of french fries.
Each time this reaction occurs, whether it's glucose entering the TCA cycle or fructose generating reactive oxygen species at a faster rate, it can result in cell dysfunction and death unless it is counteracted by antioxidants. These antioxidants are found in the peroxisomes within your cells, where reactive oxygen species go to die. Therefore, it is crucial to have an adequate antioxidant capacity to prevent further damage. This is referred to as ORAC, which stands for Oxygen Radical Absorbance Capacity, is closely associated with antioxidants and their ability to protect the human body against the detrimental impact of free radicals on healthy cells. It quantifies the overall capacity of antioxidants to prevent and eliminate the harmful effects caused by these unstable molecules.
So, where do you obtain these antioxidants? You can get them from the air you breathe and from the foods you consume. So, which foods are rich in antioxidants? Broccoli, spinach, carrots, and potatoes possess a significant amount of antioxidants, as do artichokes, cabbage, asparagus, avocados, beetroot, radish, lettuce, sweet potatoes, squash, pumpkin, collard greens, and kale. Incorporating a wide variety of spices into culinary preparations is beneficial as well.
Some of the big questions are: how do you know your gut health is sufficient to absorb these? How do you know how much you need and on what frequency? You don't know until you obtain an individualized analysis.
3. Mitochondrial Dysfunction
Mitochondria, the powerhouses of our cells, play a crucial role in burning energy. Their main job is to convert energy sources into carbon dioxide, which we then breathe out. However, not all mitochondria are able to perform this function effectively. Many factors can interfere with their function, leading to mitochondrial dysfunction. A recent study conducted by Samir S. Dick in Ron Khan's Lab at Joslin, Harvard, explored the impact of different substrates on mitochondrial function. They compared glucose and fructose as substrates and made some interesting discoveries. Glucose is activated by two enzymes that improved and increased mitochondrial beta oxidation. One of these enzymes, amp kinase, is a fuel gauge for liver cells and also plays a role in generating new mitochondria.
Additionally, glucose increased the activity of an enzyme called HADH, which is essential for fatty acid beta oxidation. In summary, glucose promotes mitochondrial beta oxidation, which is beneficial for our cells. On the other hand, fructose inhibits three mitochondrial enzymes. It interferes with amp kinase, rendering it inactive and inhibiting its function. Fructose also inhibits an enzyme called acad L acyl COA dehydrogenase, which is necessary for initiating fatty acid beta oxidation. Lastly, fructose consumption leads to an increase in uric acid, which inhibits an enzyme called cpt-1a carnitine Palmetto transferase. In conclusion, while glucose supports mitochondrial function and promotes energy burning, fructose hinders mitochondrial activity. This study sheds light on the importance of substrate choice and its impact on mitochondrial health.
The process of regenerating carnitine and is crucial because it acts as a shuttle mechanism, allowing fatty acids to enter the mitochondria for beta oxidation. However, when it comes to fructose, the story changes. The presence of fructose in the diet actually inhibits beta oxidation, which is not good news. Renowned researcher Ron Khan himself emphasized the negative impact of high fructose intake on liver metabolism and fat burning. Adding fructose to the diet leads to increased fat storage in the liver, which is detrimental to overall body metabolism. So, it's safe to say that fructose is not a good sugar option. While glucose is relatively better, it still has its own effects on chronic metabolic diseases due to its impact on insulin levels. It's a bit of a trade-off.
4. Insulin Resistance
Insulin resistance is a complex phenomenon that is often associated with obesity. However, recent research has shown that this assumption is not entirely accurate. The metabolically healthy obese individuals have demonstrated that obesity does not always lead to insulin resistance. When examining the relationship between BMI and insulin resistance, it becomes clear that there is a hyperbolic relationship. This means that as weight increases, insulin resistance also increases, regardless of BMI. While this is true, it is important to note that within each BMI category, there are individuals who can be either insulin sensitive or insulin resistant. Determining who falls into which category is not always straightforward. Just because someone has a higher BMI does not automatically mean they are insulin resistant, and conversely, having a lower BMI does not guarantee insulin sensitivity.
These are separate phenomena that need to be evaluated individually. When we shift our focus from weight to insulin sensitivity and resistance as variables, we can observe that those who are insulin resistant, regardless of their BMI, are more likely to develop diabetes and heart disease. This highlights the importance of insulin resistance in these conditions. Now, how does one develop insulin resistance? There are several factors at play, but let me share with you my favorite one - the one I have extensively researched at UCSF. In a study involving 43 children with metabolic syndrome, fatty liver, and high sugar consumption, we found that their baseline diet contributed to their insulin resistance.
It is crucial to understand that it is insulin resistance that qualifies obesity, not the other way around. In other words, it is the presence of insulin resistance that truly matters when it comes to the impact of obesity on health. So, while obesity may be a contributing factor, it is not the sole determinant of insulin resistance. By focusing on insulin sensitivity and resistance as key variables, we can gain a better understanding of the relationship between weight, insulin, and overall health.
5. Membrane Integrity
Membrane integrity is a crucial aspect to understand, and a simple analogy can help illustrate its significance. Imagine when you were a child, blowing up balloons for a birthday party. Remember how the balloon would stretch when you inflated it? If you tried poking it with your finger, it would just bounce back. However, if you were to poke it with a pin, it would burst. Now, let's take this concept and apply it to the membrane of cells, including neurons. Just like the balloon, the composition of the plasma membrane plays a vital role in its integrity. The membrane has a property called membrane fluidity, which can be easily disturbed.
This fluidity is determined by cholesterol and phosphatidylcholine, with Omega-3s playing a crucial role in stabilizing it. Studies conducted by Fernando Gomez Pania at UCLA have shown that fructose, due to its effects on insulin resistance, can drive changes in membrane fluidity. However, the administration of omega-3 fatty acids can help ameliorate these changes. Omega-3s are essential structural components of cell membranes, making them more flexible and adaptable. Unfortunately, our diet lacks omega-3s and instead contains omega-6s, which are pro-inflammatory. This imbalance can lead to inflammation, which we will explore further.
6. Inflammation
Now, where does the inflammation originate from? Well, it can stem from various sources. Of course, if you have an autoimmune disease that promotes inflammation, you may experience conditions like rheumatoid arthritis or lupus. However, the truth is that a majority of the inflammation in our bodies arises from our gut. Yes, our gut plays a significant role in this. Our gut has two barriers that work together to prevent all the harmful substances in our intestines from wreaking havoc on our system.
Firstly, there's the mucin layer, which acts as a protective shield on top of the epithelial cells, serving as a mechanical barrier.
Secondly, there are proteins called tight junctions that hold the intestinal cells together. These tight junctions are crucial in maintaining the integrity of our gut. Now, let's talk about celiac disease for a moment. It's a condition where there's a defect in a specific protein called zonulin, which is responsible for maintaining the tight junctions. When these tight junctions fail, harmful substances can enter our portal system, travel to the liver, and cause inflammation there. So, you can see that the gut is a primary entry point for inflammatory substances like lipopolysaccharides, cytokines, and even whole bacteria. The liver then has to work hard to clear these substances, leading to liver inflammation.
Now, here's an interesting twist. It turns out that fructose, found in many sweet treats, can actually impair those tight junction proteins, making them dysfunctional. On top of that, fructose also wreaks havoc on our intestinal microbiome, which I'll explain further on the next slide. So, not only does fructose mess with the tight junctions, but it also causes trouble for our gut bacteria. But wait, there's more!
The lack of fiber in our diet also contributes to a defect in the mucin layer. You see, fiber plays a crucial role in protecting that mucin layer. Without enough fiber, the bacteria in our gut start feasting on the mucin layer, using it as their food source. It's like a buffet for them! And when fructose enters the picture, it only adds to the problem. So, in summary, the inflammation in our bodies often originates from our gut. The mucin layer and tight junctions play a vital role in keeping harmful substances at bay. However, factors like fructose and a lack of fiber can disrupt these protective mechanisms, leading to inflammation.
Fructose plays a crucial role in exacerbating various health issues, including bacterial and lipopolysaccharide translocation into the portal vein, leading to liver-related problems such as hepatic insulin resistance, inflammation, fatty liver disease, and chronic metabolic disease. Interestingly, fructose has been found to be more detrimental to immune cells than glucose. While glucose is easily converted into lactate within immune cells, fructose interferes with this process and impairs the cell's ability to respond to glutamine, which is an immune suppressant. As a result, immune cells become hyperactive, as indicated by the increased levels of tnf alpha, il1 beta, and il-6.
However, the administration of rapamycin can counteract this effect, highlighting the protein synthetic nature of the immune cell response to fructose. Removing fructose from the diet has shown to improve inflammation, as demonstrated in studies conducted on patients with lupus and rheumatoid arthritis. In fact, the interaction between group a Streptococcus and anti-ideotypic antibodies contributes to rheumatoid arthritis, and fructose promotes the growth of group a strep more than glucose does. Therefore, by reducing inflammation in our intestines and addressing hepatic insulin resistance and chronic metabolic disease, we can potentially alleviate the severity of autoimmune conditions.
7. Epigenetics/Mutation
None of them possess any effective medications, with the exception of making dietary changes. The only solution that truly yields results is altering one's diet. The process of sugar molecules attaching to proteins, known as glycation, is primarily caused by the consumption of carbohydrates and fructose, while lacking fiber in one's diet. Consuming glucose and fructose drives oxidative stress, which is an imbalance between free radicals and antioxidants. The consumption of fructose primarily causes mitochondrial dysfunction, which disrupts energy production in cells. Unhealthy fats, such as omega-6 fatty acids, and a deficiency in essential micronutrients contribute to various health issues.
Insulin resistance, a condition where cells fail to respond properly to insulin, is driven by the consumption of fructose and branched-chain amino acids like leucine, isoleucine, and valine, commonly found in corn-fed beef, chicken, and fish. A lack of omega-3 fatty acids, essential for cell function, leads to membrane instability. Inflammation can be attributed to the consumption of carbon and gluten. Carbohydrates, gluten, and certain omega-6 fatty acids contribute to inflammation. Fructose consumption and a lack of fiber also play a role in epigenetics, the study of how genes are influenced by environmental factors. Methylation, a process that affects gene expression, is hindered by a deficiency in folic acid and vitamin B12. Lastly, an overall lack of folic acid and vitamin B12 can have a significant impact on one's overall health.
8. Autophagy
This concept is similar to how you take out the garbage every tuesday. As you age, autophagy decreases (decreased emptying of metabolic garbage), which can lead to various health issues such as cell death, cancer, problems with the immune system, cardiomyopathy, aging, infectious diseases, fatty liver, and neurodegenerative diseases. To improve your health and prevent these problems, it is important to increase autophagy. Autophagy has numerous benefits, including improving immune responses, reducing inflammation, changing cell death rates, reducing cellular senescence, and preventing oncogenesis. One key factor in regulating autophagy is AMP kinase. When AMP kinase is functioning properly, autophagy occurs, but when it is not working, autophagy stops.
The main cause of this disruption is ultra-processed food, which now accounts for a significant portion of the American diet.
In fact, 62 percent of all food consumed in America and 67 percent of all kid food consumed in America is ultra-processed. Refined sugar, a major component of these foods, is not only found in obvious sources like candy, cakes, ice cream, and sugary beverages, but also in fruits, vegetables, starchy foods, meat, fish, eggs, dairy products, fats, sauces, and salty snacks. The food industry intentionally adds sugar to make their products more addictive, as the fructose molecule stimulates dopamine in the reward system, leading to cravings for more. This addiction to processed food has contributed to the increase in BMI and obesity rates in Europe, as well as higher mortality rates.
Contrary to popular belief, whether a diet is high in fat or high in carbs does matter.
Your microbiome breaks down the carbohydrates because you've prevented their early absorption. The fiber forms a gel-like structure inside your intestines, creating a barrier that prevents the transport of glucose, fructose, sucrose, and simple starches from the intestine into the portal vein. As a result, your liver never sees them. Even though you consumed these carbohydrates, they pass through your intestines without being absorbed.
So, what truly matters is what passes through your intestines, not just what you eat. The focus should be on the calories that make it through your digestive system.
