Janury 8, 2024
Section I
Literature Review
1) In an excellent paper by Dr. Harlan and colleagues, we see a group looking at how to modify ultra processed foods to remain tasty for consumption but also healthy.
The lead author is Dr. Rob Lustig, a pioneering Pediatric Endocrinologist from UCSF and upcoming podcast guest. From the paper: "Ultraprocessed food is established as a metabolic disruptor acting to increase adiposity, reduce mitochondrial efficiency, drive insulin resistance, alter growth, and contribute to human morbidity and mortality. Consumer packaged goods (CPG) companies are beginning to understand the detrimental impact of the food they market, and have employed substitution strategies to reduce salt, sugar, and fat. However, the harms of ultraprocessed foods are far more complex than any single component, and are not ameliorated by such simple substitutions." (Harlan et. al. 2023)
The group has three stated goals: 1) protect the liver, 2) feed the gut, 3) support the brain. These are all of the aspects of health that we have discussed for years on the podcast and in this newsletter. His group has dedicated themselves to meeting the companies at a place where they can produce food that is healthful and cost effective. An admirable desire for sure. This article is absolutely worth a full read. The paper goes on to cover 5 misconceptions of insulin resistance and chronic disease: 1) chronic disease is the inevitable result of the aging process. 2) the rise in prevalence and severity of obesity is self-determined due to an increased prevalence of the vices of gluttony and sloth. 3) obesity and chronic disease are the same phenomenon. 4) most clinicians mistakenly attribute the growing rise of non-communicable diseases (NCDs) to fat depots which are outwardly noticeable. 5) the cause of chronic disease is the quantity of the food consumed according to the metric of “calories.” (Harlan et. al. 2023)
Ultraprocessed foods are causing mitochondrial dysfunction and disease through multiple pathways: macronutrient and micronutrient composition, fiber, food additives, toxins, heat exposure, and packaging (mostly due to plastics as endocrine disruptors). These are the levers to pull on for all of us. Whole food in its original or close to original form will have the best macro and micro nutrient profile. Vegetables and fruits are our fiber source. Synthetic food additives and emulsifiers are not to be consumed. Plastics and chemicals in food, water and air are to be avoided. These are simple truths to promote health. Next week is a deeper dive into this science.
2) As we start to see more adjunctive research supporting pharmacotherapy with cofactors, we will see better clinical improvements and less side effects. In a recent publication in the Journal of Affective Disorders the authors noted that patients that were supplemented with vitamin B6 had significant improvements in mood. (Zandifar et. al. 2023) This is straight forward biochemistry. The cofactors improve enzymatic activity. "Vitamin B6 is important for the synthesis of many neurotransmitters, including GABA, serotonin, dopamine, noradrenalin, histamine, glycine, and d-serine, indicating that vitamin B6 supplementation may enhance many neurotransmitter systems. Thus, vitamin B6 supplementation can treat the impaired neurotransmitter systems in a given patient, even if the actual impaired neurotransmitter systems are not defined in that patient." (Sato K. 2018)
3) Brain derived neurotrophic factor or BDNF is a very important protein for brain growth and neuroplasticity. It is also now turning out to be a proxy for adequate omega 3 fatty acid volume in the brain. From Scientific Reports: "Enriching brain DHA is believed to be beneficial for the prevention and treatment of several neurological diseases, including Alzheimer’s disease. An impediment in assessing the effectiveness of the treatments is the lack of a reliable biomarker for brain DHA. The commonly used erythrocyte omega-3 index is not suitable for brain because of the involvement of unique transporter at the blood brain barrier (BBB). We recently showed that dietary lysophosphatidylcholine (LPC)-DHA significantly increases brain DHA, which results in increase of brain BDNF. Since there is bidirectional transport of BDNF through the BBB, we tested the hypothesis that plasma BDNF may be used as biomarker for brain DHA enrichment. We altered the brain DHA in rats and mice over a wide range using different dietary carriers of DHA, and the correlations between the increase in brain omega-3 index with the increases in plasma BDNF and the erythrocyte index were determined. Whereas the increase in brain omega-3 index positively correlated with the increase in plasma BDNF, it negatively correlated with the erythrocyte index. These results show that the plasma BDNF is more reliable than the erythrocyte index as biomarker for assessing the effectiveness of omega-3 supplements in improving brain function." (Sugasani et. al. 2020)
BDNF is critical for learning and memory especially in the hippocampus and the neocortex. The issue with BDNF is that it decreases with pathological diseases of the brain. I.e. it is a proxy for neurodegenration. As it decreases, brain plasticity is reduced and cellular function goes sideways. This is all bad news. Diet, exercise, sleep and general lifestyle choices are BDNF enhancing. Thus, if Omega 3 FAs increase BDNF volume and this is a biomarker of O3 FA brain uptake, then it would likely follow that omega 3 FAs are a very important part of the brain's healing process. (Miranda et. al. 2020)
4) What is happening to the gut microbiome when non caloric sweeteners like aspartame are consumed. The authors looked specifically in the duodenum of the small intestine where post acid hydrolyzed food is mixed with bile and pancreatic enzymes before entering the jejunum and remainder of the small intestine. This Cell study compared aspartame, non aspartame non caloric sweeteners and a control on the microbiome of the duodemum. They noted that both non caloric sweeteners and asparatame reduced biodiversity and also increased the proportion of gram negative rods like e coli and klebsiella. (Hosseini et. al. 2022)
The key to this study is two fold: 1) weakened biodiversity is a proxy marker for leaky gut and inflammation over time, i.e. not good. 2) the rise in gram negative rods is a main driver of lipopolysaccharide release into the systemic circulation due to a concentration gradient and the associated leaky gut. The LPS in the blood stream is a direct trigger of toll like receptor activation, immune activation subsequently and mobilization of lipoproteins including LDL and HDL to clear the LPS. The end result is elevated LDL levels which are Apo B containing and a direct link to cardiovascular disease.
Have a great week,
Dr. M
Sugasani Nature Scientific Reports
