For those who haven’t followed my online happenings (@kcklatt), I started talking about nutrition science back in 2014 when I was beginning my dietetics and PhD journey. At the time, the media raged with weekly, if not daily, headlines about nutrition, the FoodBabe was huge, there were ongoing conversations in the academic literature and general public about GMOs, and looking back, we were in the early decade following the defunding of a lot of mechanisms the field of nutrition has historically relied upon to do nutrition science (read: it was a hotbed of controversy as different funders and approaches to science predominated). I enjoyed blogging during these times, and it many ways it shaped how i think now.
I completed my PhD in Molecular Nutrition at Cornell in 2018 and my Dietetic Internship at the NIH Clinical Center in 2019. Blogging died off for me during those times - between writing a dissertation, contributing more to scholarly literature, doing an unpaid internship at a government affiliated institution and fearing being dismissed over a controversial post all killed my desire to blog a bit. I admittedly got tired of feeling like I said the same things - the limitations of nutrition science juxtaposed with the hype & hope around it from various cultural/political/scientific actors were a bit jarring for me. I also had my fair share of run-ins with rigor and reproducibility issues in science, and saw pretty up close and personally how the incentives in the scientific structure (i.e. wanting to be an expert, rushing to generate data to get grants) led folks to do some pretty problematic things with data. You come into science & academia thinking its a righteous institution out to help society/patients, but the close up view, especially in the day to day of hypercompetitive, resource constrained biomedical sciences, can be really disheartening. It not only killed my desire to blog but had me considering other career paths.
As i’ve taken a few years off from blogging, little has really changed in the media and scientific landscape - if anything, we’ve seen the rise of the influencer with affiliate links, profiting off of everything from anecdote to claims of ‘science’-based approaches to optimizing your health. Influencers aren’t just the Food Babes anymore - i’ve seen a huge rise in folks with meaningful credentials pedalling BS, or at the very least oversold expectations for the effects of a product, and we’ve seen more elite academic institutions and their press offices clamoring to be seen as the premiere site for rigorous scientific work, overinterpreting and overselling their own investigators findings. Watching this during the midst of the March 2020 coronavirus pandemic emergence, and how the profiteering didn’t stop as we had an overly politicized, bungled public health response, inspired me a bit to get back into talking about the science of nutrition. I was never all that professional in my blogging tbh, but this took to new heights as I found some Meme Generator apps and went to town making memes with captions poking fun at all of the happenings in nutrition, medicine, science & wellness. You can scroll back through my IG posts and probably get a solid read on my mental state at the time, but i’ve covered a lot of topics there with basic opinions on the limits of science and also some philosophical/political analysis of what drives a lot of the wellness movement.
While i’ve enjoyed IG, and continue to use twitter, neither has fully replaced blogging. The ability to long form word vomit and really break down studies/explain topics, without being constrained to an instagram caption or bizarrely long tweet thread is pretty nice. I’m not entirely sure what the future of this substack will be, other than the chaotic musings of my mind as i continue to navigate the health/wellness media space as well as academia & academic nutrition, and reflect on current happenings. If you wanna sub, expect some wonky deep dives, overly technical discussions, in the relevant historical and sociopoliticocultural context. Also memes.
Shoot me a social media DM if you wanna see a specific topic covered. A little bit more about me below for those wondering more about my perspective on science:
I had a bit of imposter syndrome when i started my PhD at Cornell, mainly due to the fact that prior to joining the program, I had set out to get a lot of experience in different areas of nutrition research. I did my BA in biological anthropology with a bend towards wanting to understand human evolution, and modern genomic/population genetic techniques with an eye towards how i could leverage that in a future career in nutrition & metabolism. I sort of bopped around when i discovered research towards the end of my junior year of undergrad - prior to Cornell, i ended up doing sitting in a human population genetics/comparative primate genomics lab (though truly i contributed little here and just sat back learning), did some rat nutrition studies with molecular/epigenetic outcomes, some psychological coding of mother-infant breastfeeding dyads (in humans), and got exposure to breastmilk analysis through HPLC. In short, it was a clusterfuck of research experiences, all 3-6months long for the most part and not really giving me the same level of experience of a lot of my colleagues who had spent a couple years consistently in a lab, had mastered a few techniques, and could hit the ground running in their new PhD research labs. Looking back, i don’t think there’s a right way to prep for your PhD, but at the beginning, I was acutely aware of the need to master new techniques and get some publications (i.e. academic capital).
In my PhD, I ended up having functional co-chairs on my dissertation committee, working partially in a human nutritional biochemistry lab focused on micronutrient metabolism primarily, with an emphasis on reproductive life stages (i.e. pregnancy, lactation). The other lab i worked in focused on reproductive endocrinology, looking at certain g protein coupled receptors and their downstream intracellular signaling proteins on the hypothalamic-pituitary-gonadal axis, as well as the placenta. I spent the first year of my PhD phenotyping a transgenic mouse lacking a homeobox domain-containing protein as a potential model of placental insufficiency and pre-eclampsia. Unfortunately, after a years worth of work doing everything from surgically implanting radiotelemeters that had to be turned on daily at 6am to putting mice in metabolic cages to collect urine, there wasn’t much of a reproducible phenotype and the project was canned. It wasn’t a bad thing ultimately - in the distress of the project collapsing 11 days before what should’ve been my qualifying exams, i was wondering through the literature looking for another project idea that could link a lab focused on choline/reproduction and a lab focused on various signaling pathways/reproduction, and stumbled upon what would ultimately be a huge part of my dissertation. At the same time, we were writing grants and had a lead on some industry money to fund another human choline intervention trial during pregnancy.
I was extremely fortunate that the stars sort of aligned - the paper that I found that would contribute to my dissertation described a phosphatidylcholine species (PCs have a common choline headgroup but vary in their fatty acid composition) that bound an orphaned nuclear receptor, LHR-1 (nuclear receptors are a family of protein transcription factors that influences gene/protein expression and are known to have a domain of their protein structure that binds certain chemicals/hormones to influence their activity) known to regulate bile acids ( a topic we were relatedly looking at in the basic science lab I was working in). This specific phosphatidylcholine was enriched with 2 lauric acids (dilauroylphosphatidylcholine; DLPC) and I saw it had an “ah-hah!” moment. Fortunately, one of the world experts in this nuclear receptor was visiting campus to give a talk that week and I met with her to speak about DLPC as a potential ligand for LRH-1. I had noted that few people described DLPC in any cellular/physiological context, which the speaker confirmed - basically, DLPC bound & activated LRH-1 but wasn’t really relevant to the cell. (The DLPC that was tested in the seminal papers was extracted from bacteria & purified). Ultimately, I went on in my dissertation to show that DLPC was very relevant in physiology - the problem was that the 12 carbon fatty acids (lauric acid) that on the PC molecule are quite rare in the cell, but can be abundant in the diet if one consumes tropical oils. Humans have historically eaten a lot of lauric acid, especially those who live in tropical regions and consume coconut/babasu/palm kernels, and we all eat lauric acid in infancy, as its a uniquely high component of breastmilk fat. In my dissertation, I put lauric acid on cells (cell culture media is also deficient in lauric acid) and saw DLPC being readily made by numerous cell lines in just a few minutes. Feeding laurate to mouse models led to DLPC being acutely made in their intestines in just one feeding, and after chronic feeding, you could see DLPC in a bunch of tissues. And in a human controlled feeding study, you could see DLPC in postprandial serum taken from human participants after eating a coconut oil containing smoothie, but not after consuming one containing olive oil. This project was great in that it required me to work across cell, animal and human subjects research, allowed me to dive deep into liquid chromatography mass spectrometry methods and lipid analysis, use stable isotopes, and try out some gene knockdown via siRNA.
The other half of my dissertation ended up nicely complementing this DLPC story, focusing instead on PC species enriched in the omega 3 docosahexaenoic acid (one of the beneficial omega 3s in fish oil). Production of PC can occur through 2 pathways - all cells have the CDP-choline pathway of PC synthesis, whereas hepatocytes express the PEMT pathway, which tri-methylates phosphatidylethanolamine (PE), generating a PC. The PEMT pathway produces PC species that are more enriched in DHA, and use methyl groups to do so. We hypothesized that methyl groups were limiting in human pregnancy and led to submaximal PEMT activity and PC-DHA synthesis. DHA that we eat in the diet/supplement gets absorbed into the body and incorporated into different lipid species - it can stay a free fatty acid, getting esterified to cholesterol, be incorporated into phospho/sphingolipids or lysophospholipids. All of these forms of DHA are probably important during pregnancy, but the PEMT pathway is known to be a majorly induced pathway during pregnancy (in response to the rising estrogen levels) and the PEMT knockout mouse is known to have reduced DHA in the brain during development - thus, it looks like PEMT in the maternal hepatocyte is important for DHA in the developing fetus. We undertook a randomized controlled trial to assess whether choline supplementation, a major source of methyl donors in the diet, would influence PEMT activity and improve markers of PC-DHA and DHA status/availability. Additionally, we use isotopically labeled choline to track choline’s metabolic fate and its partitioning towards the PEMT pathway. This was a big undertaking for any research group, let alone a relatively smaller one in upstate NY, and involved coordinating a lot of pregnant participants and obtaining their blood longitudinally throughout pregnancy, as well as blood and placenta at the time of birth (parturition). Our hypothesis indeed turned out to be correct and choline supplementation during pregnancy improved PC-DHA output into plasma, DHA status markers and was associated with isotopic enrichments indicative of increased PEMT activity. We published these results in AJCN.
Following my dissertation, I wanted to round out the laurate paper and get some more molecular experience, and went off to do my postdoc at Baylor College of Medicine in the lab that found that DLPC was a ligand for LRH-1. This lab had different tissue specific LRH-1 knockout mice that could allow me to advance the lauric acid story further, and look for not only ligand development but really strong evidence of activation that lauric acid feeding leads to LRH-1 target gene activation, and that this is not present in mice genetically lacking LRH-1 and also in mice not consuming laurate. This led to a 3-x-2 feeding study that i completed (largely throughout the hobbled COVID pandemic), feeding diets with lauric acid at 10% of kcals vs isocaloric palmitic acid (another common saturated fat) or oleic acid (the most common unsaturated fat) to mice either having hepatic LRH-1 or lacking it. We were able to see that lauric acid fed mice had higher target gene expression in only the mice that exhibited hepatic LRH-1, relative to those consuming palmitate or oleate. In the mice genetically lacking hepatic LRH-1, all 3 diets showed similar and lower target gene expression, indicating that laurate is unique in inducing LRH-1 target genes and it only happens when LRH-1 is present. This rounded out that paper which is under review, and teas up studying lauric acid-induced LRH-1 activity in a bunch of other contexts, some of which we are exploring.
I work collaboratively with others on some additional research projects as well, including a controlled feeding study in pregnant women in Tanzania looking at Vitamin B12 status across pregnancy in response to supplementation, have some projects related to novel/weird fatty acids that the placenta seems to make that we accidentally stumbled onto, and collaborate with some epidemiologists to further look at dietary choline’s link to health, while also taking into account genetic factors that influence the response to consuming different amounts of dietary choline. I continue to work to this day in a lab primarily focused on nuclear receptors, and in addition to studying lauric acid-nuclear receptor interactions, am exploring additional dietary components and their interactions with this class of proteins.
Apart from research, I maintain a small clinical practice seeing specialized patient populations, primarily those with cardiometabolic and GI diseases, as well as serving as an editor at the American Journal of Clinical Nutrition and a textbook editor for Biochemical, Physiological and Molecular Aspects of Human Nutrition, 5e. I also serve as a mentor in the Diversify Dietetics program formally, and informally mentor a number of graduate, PhD and dietetic trainees in and outside of my institution.
This is a bit of a rapid (though still lengthy) discussion of my training and PhD experience, but gives you some insight into how i approach thinking about nutrition.
-KCK