Today’s episode was filmed at the Future Directions in Choline Symposium put on by the University of North Carolina Nutrition Research Institute.

Our day two episode opens with Dr. Eric Ciappio and Dr. Jonathan Bortz of Balchem, summarizing day one’s focus on pregnancy and early life and previewing day two’s focus on the latest choline research targeting adult nutrition. (1:03)

The next guest on our roster is Dr. Mark Manary, a professor of pediatrics at the Washington University School of Medicine. Mark’s symposium talk discusses choline and food aid. Food aid products are specially designed to address needs from crisis situations. These specialized food aid products are standardized to meet great deficiency or inadequacy needs. On the most extreme side, there is a product called ready-to-eat therapeutic food for children who are starving to death. Other food aid products include those for severely underweight children. Dr. Manary’s research consists of clinical trials in sub-Saharan Africa that include different nutrients in food aid to see if there are improvements in children’s responses. One trial with the inclusion of DHA found a 6-15 IQ point difference by adding fish oil or DHA. Mark hypothesizes that a doubling of that effect will be observed when choline is added. (6:42)

Dr. Rima Obeid from Saarland University Hospital in Homburg, Germany, joins us next. Her symposium presentation focused on choline and pregnancy outcomes. Their research group has found that low or insufficient amounts of choline in the mother’s diet during pregnancy are associated with a higher risk for serious birth defects in babies and that the liver health of the infants is also negatively affected by low choline intake of the mother during pregnancy. Rima’s future research includes investigating the impacts and interactions of folate and choline consumption during pregnancy on neural tube defects such as spina bifida. In another study, she will focus on the relationship between the severity of congenital heart defects compared to neural tube defects. In particular, they wish to look at the association with low choline in the blood of the children, the mother and the father, because a pilot study suggests a family pattern, which could be due to some genetic background. (17:18)

Our next guest is Dr. Susan Smith, Deputy Director of the University of North Carolina Nutrition Research Institute. One of her presentations centered on choline genetics and cognition. Her research has found genetic variation in choline uptake from the diet. One research question was, “Are there choline variants that affect how powerful that choline is in treating a disease condition?” In particular, Dr. Smith was investigating if choline could be used to treat children who have brain damage from prenatal alcohol exposure, and the answer is yes, it’s very helpful. Then, they evaluated if some children benefit more than others and found that there is a gene variant that affects how efficiently choline is absorbed from the diet. Children with the variant that reduced choline uptake benefitted the most from supplemental choline. In addition, there was an impact of the gene variant on cognitive function regardless of prenatal alcohol exposure. Children who carried one or two copies of this particular variant had reduced cognitive performance as compared to those children who were lucky enough to be born with the other variant. While we still don’t have a blanket recommendation for how much choline pregnant women should consume, Dr. Smith’s message to pregnant women is that eating enough choline lets your baby achieve its full potential. (23:32)

Dr. Isis Trujillo-Gonzales and Dr. Evan Paules, both with the University of North Carolina Nutrition Research Institute join us. Isis focuses on choline and brain/eye development, while Evan focuses on choline and metabolic health. Dr. Trujillo-Gonzales’s research has found that the neurons in the eye that receive light and connect to the rest of our brain are impacted by choline absorption. Her lab has also investigated the mechanism of action for choline’s effect on brain development. The stem cells in the brain that give rise to neurons are very sensitive to choline availability. If a pregnant mom is not consuming enough choline, these cells in the baby’s brain are not proliferating adequately. Choline is important in the microRNA that fine-tunes the regulation of this pool of stem cells. Dr. Paules’s research is focused on the metabolic symptoms of obesity and the impact of choline on them. For example, giving choline to someone who is deficient can ameliorate the symptoms of fatty liver disease.  One area emerging in his work is the loss of lean mass as people age. It appears that increased loss of lean muscle is observed in people who aren’t consuming adequate choline. This suggests that as we age, making sure we have sufficient amounts of choline intake may help prevent the loss of lean muscle tissue. (32:58)

Dr. Bryan White with the University of Illinois is our next guest, and his area of interest is the microbiome. In particular, he discusses the role of the microbiome in TMAO production. TMAO (trimethylamine N-oxide) is a metabolite that has been associated with cardiovascular disease. In short, the microbiome produces TMA (trimethylamine), which is converted to TMAO in the liver. Some of the seminal TMAO literature suggests that there is a diet effect on the production of TMAO and that diet changes the microbiome so that more TMAO is produced in the bloodstream. When it comes to microbiome research, there are generally four questions that can be asked about the microbial community: 1) Who's there? 2) How many of them are there? 3) What can they do (given their genetic potential)? and 4) What do they do? The seminal research used 16s ribosome technology to evaluate which microbes were present and their abundance in the microbiome of people consuming omnivorous versus vegetarian diets. It stated that there was a correlation between diet and blood levels of TMAO. Dr. White took the small read archives of that manuscript (the sequencing they did of 16s ribosomes) and got the opposite results of the original paper. (42:25)

Our next guest is Dr. Jonathan Bortz with Balchem Corporation, whose presentation was titled, “TMAO and Choline: A Mechanistic Perspective.” In the last several years, there have been concerns about choline advanced by a group of investigators who have claimed that excessive intake of meat, eggs, and other animal-source foods (resulting in choline and/or carnitine upon digestion) generate a substance in the blood called TMAO, trimethylamine oxide. Their hypothesis has been that TMAO has a negative effect on the cardiovascular system and has been associated with a high incidence of cardiovascular disease. However, Dr. Bortz presented multiple examples of how the concerns about choline with respect to TMAO having a causative effect on cardiovascular disease really cannot be supported. In other words, choline does not represent a risk to any users, young or old. (51:42)

Dr. Julia Maeve Bonner with Sanofi joins us next to give an overview of her presentation about choline and Alzheimer’s disease. In her postdoctoral work at MIT, Dr. Bonner focused on the apolipoprotein E (APOE) gene, which is involved in making a protein that helps carry fat in the bloodstream. Dysfunction in this process is thought to contribute to the development of Alzheimer’s. APOE4 is the most highly validated risk factor for Alzheimer’s. Dr. Bonner wanted to understand what is happening in APOE4 high risk allele compared to the APOE3 neutral risk allele of this gene in brain cells (astrocytes) in culture. She found that the APOE4 astrocytes accumulated neutral lipids, particularly triacylglycerols, to a much higher degree than APOE3 cells. These lipid droplets is associated with many different dysfunctions in the cell that can be associated with neurodegeneration. If APOE4 cells were grown in a choline-rich media, the lipid imbalance was shifted much closer to the APOE3 cells. Dr. Bonner’s group was able to pinpoint that phosphatidylcholine synthesis is the mechanism of action by which choline supplementation had the lipid-shifting effect in APOE4 cells. She has also studied choline supplementation in mice that have Alzheimer's disease genes knocked in where they accumulate the plaques that we see in human brains in Alzheimer's disease. In the background, they also have the human APOE knocked in, which means that they're expressing either APOE3 or APOE4. Again, they saw a protection against the accumulation of some of the Alzheimer’s-related damage as well as a lipid shift similar to the brain cell cultures. (1:03:00)

To summarize the Future Directions in Choline Symposium, Dr. Dr. Stephen Hursting and Dr. Susan Smith with the University of North Carolina Nutrition Research Institute join us. They give their perspectives on the advancements of the field of choline research and leave us with the take-home message that choline is a critical nutrient for the entire healthspan. (1:22:27)

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