What do you feel are the biggest unknowns in nutrition/weight management?

I'll start as I follow a lot of the literature, in no particular order:

1. The impact of food processing on the food matrix and nutrient quality. There is some research on this but it's quite scattered and difficult to find a comprehensive overview other than it's generally better to minimize heat/time cooking/light exposure to avoid undesirable oxidation.
2. The benefits vs harms of organic (or more specifically exogenous pesticide-free) food long term. Thus far there are only significant harms seen with organophosphate consumption in pregnant women and young children, but with environmental changes over time it's unclear how this will continue to evolve.
3. The impact of exercise on TDEE (had to include this to fit in with the forum). More seriously, is there an optimal PAL (TDEE/REE) to help stave off some of the compensatory increases in hunger that occur with weight loss? This review proposes 1.7-1.8, but the authors acknowledge we need a lot more evidence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835968/
4. Being in ketosis seems to suppress hunger and ghrelin; are there any other dietary or exercise modifications that can consistently alter gut hormone secretion to aid hunger/satiety?
5. There is still a lot of controversy about the different types of saturated fat as well as sodium intake. Same with egg intake. Same with dairy regarding prostate cancer risk. Same with processed meat and unprocessed red meat.
6. There are still outstanding questions regarding protein intake (amounts, timing, importance of leucine per meal, the long-term impact on these, etc).
7. The time-restricted eating literature (what most people here call intermittent fasting) shows lots of promise but studies are small, and there are only ~7 in people engaging in resistance training. These typically show that lean mass is preserved, and this literature overall shows promise. Whether this translates to larger studies and longer-term remains to be seen.
8. What makes constitutionally thin people different? The literature is sparse overall but these individuals (generally defined as BMI <18.5 with no medical issues (other than decreased bone mass) who struggle to gain weight) may hold the key to treating the obesity epidemic.

Curious if others have thoughts.


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