January 15, 2024
Sugar, Immune Health and Two Studies
Let us start right out of the gate with two studies. #1: Here is the abstract from European Journal of Clinical Nutrition: "Milk contributes with saturated fat, but randomized controlled trials (RCT) on the effects of dairy on the risk of type 2 diabetes (T2D) where dairy is given as whole foods are scarce.
The objective of our study was to investigate the long-term effects of semi-skimmed milk on insulin sensitivity and further to compare milk with sugar-sweetened soft drinks (SSSD). A secondary analysis of a 6-month RCT with 60 overweight and obese subjects randomly assigned to 1 L/d of either milk (1.5 g fat/100 mL), SSSD, non-calorie soft drink (NCSD), or water was conducted. Insulin sensitivity was evaluated by oral glucose tolerance test (OGTT) and plasma free fatty acids. Second, fasting blood lipids, blood pressure, and concentration of plasminogen activator inhibitor-1 were assessed. There were no differences between milk, SSSD, NCSD, and water on insulin sensitivity assessed by OGTT (Matsuda Index, fasting, and area under the curve glucose, insulin and homeostasis model assessment values). SSSD increased total cholesterol compared to NCSD, and triacylglycerol compared to NCSD and water . None of the other parameters differed significantly between the groups. In conclusion, there were no differences in effect between intake of milk, SSSD, NCSD, and water (1 L/d) for 6-month on risk markers of T2D in overweight and obese adults. As a secondary analysis, these results need confirmation in future studies." (Engel et. al. 2018)
#2: From the American Journal of Clinical Nutrition: "The consumption of sucrose-sweetened soft drinks (SSSDs) has been associated with obesity, the metabolic syndrome, and cardiovascular disorders in observational and short-term intervention studies. Too few long-term intervention studies in humans have examined the effects of soft drinks. We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition (in liver and muscle tissue). Overweight subjects (n = 47) were randomly assigned to 4 different test drinks (1 L/d for 6 mo): SSSD (regular cola), isocaloric semiskim milk, aspartame-sweetened diet cola, and water. The amount of intrahepatic fat and intramyocellular fat was measured with 1H-magnetic resonance spectroscopy. Other endpoints were fat mass, fat distribution (dual-energy X-ray absorptiometry and magnetic resonance imaging), and metabolic risk factors. The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat, skeletal muscle fat, visceral fat, blood triglycerides, and total cholesterol. Total fat mass was not significantly different between the 4 beverage groups. Milk and diet cola reduced systolic blood pressure by 10–15% compared with regular cola. Otherwise, diet cola had effects similar to those of water. Conclusion: Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk, diet cola, and water. Thus, daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases." (Maersk et. al. 2012)
What do these studies mean? #1 - There was no difference between the milk, sugar based beverages and sugar free or non calorie soft drink and water on type 2 DM development over 6 months. This says nothing about chronic use (greater than 2 years or longer) and DM development. However, the SSSD group had significant increases in triglycerides and cholesterol. Why? Because the SSSD group, triggers fructose metabolism in the liver and that leads to all of these changes that are metabolically unhealthy. Study #2 - noted significant liver fat, muscle fat and abnormal lipids for the SSSD group. These findings are reflective of the fact that fructose is driving metabolic syndrome type changes that over time are very detrimental to health. Dr. Rick Johnson's work is pivotal here. It is the volume of fructose that hits the liver via the portal vein from the small intestine that is the key to the fat deposition. The route that is the worst for the body is liquid fructose as soda, sweet tea, juice, etc....
Fructose delivered as fruit in normal volumes protects the liver from the fructose onslaught as the fiber in the fruit and the associated foods slows digestion allowing enzymes in the intestine to break down much of the fructose sparing the liver. This is the key. Limiting the volume of fructose that reaches the liver is critical. Thus, these two beverage studies are important from that perspective. Keeping the liver safe is key.
More on sugar and metabolism...
What is happening when the sugar level rises high in the blood post meal? What is the immune system's view of excess sugar? Any amount of time that blood sugar levels remain high, i.e. greater than 180 mg/dl, proteins will crosslink and get permanently bound to sugar producing a advanced glycosylated end product (AGE) which is massively stimulating to inflammation via the immune system. They bind to RAGEs which are AGE receptors that are direct triggers for nuclear factor kappa B which is a super potent immune inflamer leading to lots of reactive oxygen species which directly damage local cells. NFkB is also a chemical activated by chronic stress. See a pattern here. Oh and by the way, this process also makes antibodies, which are proteins, more sticky and more prone to immune activation leading to possible self tissue responses which generate autoimmunity. Sugar is also burned in the mitochondria of cells, especially the muscle cell, for energy. The byproduct of the chemical reaction that burns glucose into ATP or our preferred action energy is also the reactive oxygen specie.
Let us take a deeper look at the mitochondrion in hyperglycemia and insulin resistance. Damage and dysfunction in skeletal muscle mitochondria is a major precursor to all patients that have insulin resistance and Type 2 diabetes mellitus. When mitochondria burn fat or glucose as fuel, the burn is performed in the electron transport chain that produces ATP and liberates water and superoxide or hydrogen peroxide. These oxygen based molecules are incredibly damaging to the actual mitochondria in excess. Again, this is only an issue in excess, not at baseline normal historical diets.
From Endocrinology: "A decrement in mitochondrial number and electron transport chain activity in T2D and obese individuals compared with lean volunteers. A deterioration of mitochondrial function in skeletal muscle obtained from obese type 2 diabetic subjects. Non-responsiveness of muscle mitochondrial ATP production to high-dose insulin infusion in type 2 diabetic subjects, suggesting impaired response to insulin and reduced mitochondrial function. A modest decrease in mitochondrial ATP synthesis rates in nonobese patients with T2D and in nondiabetic older individuals when compared to nondiabetic young groups under fasting conditions and after insulin stimulation. Lower mitochondrial function caused by a reduction of basal ADP-stimulated and intrinsic mitochondrial respiratory capacity in type 2 diabetic subjects when compared with age- and BMI-matched control subjects. Excess mitochondrial ROS production and reduced mitochondrial function are enhanced by elevated FAs and/or hyperglycemia. Mitochondrial ROS attenuate insulin action in adipocytes, myotubes, and mice, and abolish insulin-stimulated GLUT4 translocation in 3T3L1 cells by interfering with the insulin-mediated redistribution of IRS-1 and PI3-kinase." (Sangwung et. al. 2020)
The mitochondria and the metabolism within is turning out to be super critical to understanding and preventing diseases like metabolic syndrome. In order to support the struggling mitochondria under attack by the high sugar intake, one should look to antioxidants. The primary antioxidant in the body to deal with the reactive oxygen species is the chemical glutathione. Glutathione is necessary for dealing with all xenobiotics, including air pollution, water and food pollution and chemicals in general. A highly taxed glutathione system is a net inflammation generator as the overwhelmed mechanism cannot clear all irritants leading to mitochondrial and cellular dysfunction. Thus, any decision, lifestyle wise, that drives up blood glucose levels will cause immune activation that is unhealthy over time. However, toxin exposure via food, air or water also taxes this system. It truly is a multi pronged reality. You can support this system via diet primarily but also through supplements like N acetyl cysteine, liposomal glutathione, vitamin C, and polyphenolic blends like OPC, oligomeric proanthocyanidins.
While I am not going to take a deep dive here, the microbiome is massively at play here. The intestinal bacteria all play a contributory role in glucose metabolism and human health. Diet is the most important influencer of the microbiome next to antibiotics. The influence of fiber is massive. There are supplements that are showing benefit here as well. Berberine is an herb that modulates the microbiome and offers better glucose metabolism action presumed through alterations in the microbiome. Probiotics like Pendulum's glucose control are loaded with akkermansia and other bacteria and are modulating glucose metabolism. Data has noted significant drops in hemoglobin A1c's in subjects over 6 months. (Perraudeau et. al. 2020)
Ultimately, the take home point remains food first always followed by exercise followed by stress and toxin exposure reduction and then followed by targeted supplements based on dysfunction and need.
Resolution takes time and effort. Avoid sugar and non sugar sweetened beverages as much as possible.
Be Resolute,
Dr. M
