Mendelian randomization (MR) was partly a response to the many epidemiological studies suggesting vitamins were protective against various diseases, only for randomised trials to be null. The story of how fallacious MR attempted to resurrect the spurious claims here academic.oup.com/ije/article/...

It was a rewarding labour of love to work on this paper with a fantastic team of authors, “Understanding Treatment Response Heterogeneity Using Crossover Randomized Controlled Trials: A Primer for Exercise and Nutrition Scientists”. @hk-ijsnem.bsky.social journals.humankinetics.com/view/journal...

New insights into glycogen recovery in endurance athletes 🧵

1️⃣ Our new study in The Journal of Physiology tested how muscle + liver glycogen recover after exhaustive cycling in well-trained cyclists.

The ideal, of course, is to have randomisation embedded into routine practice … then, the real world data of the future will be randomised data giving the best of both worlds 9/9

There has been a lot of debate recently about the promise of real world data - the routine (observational) data collected on patients eg  treatments received, clinical outcomes etc – for estimating treatment effects. But can they deliver? 1/9
#MethodologyMonday #123

New paper!

Do ketone esters affect post-exercise recovery?

doi.org/10.1007/s003...

#ketones #exercise #sports #nutrition #recovery

🚨 3-year Post-doc opportunity at the Centre for Nutrition, Exercise and Metabolism

Opportunity to lead on an RCT involving symbiotic supplementation and ketogenic diets

www.bath.ac.uk/jobs/Vacancy...

Building in our prior work

pubmed.ncbi.nlm.nih.gov/39106867/

This is a very interesting study comparing physiological variables between two phases of the menstrual cycle across two whole cycles. The design resembles a replicate crossover trial which enables proper study of individual responses. physoc.onlinelibrary.wiley.com/doi/10.1113/...

This is, however, not clever or safe writing, it is a bad collective habit that needs to stop. Not by avoiding references to causality but by clear referencing to it

pubmed.ncbi.nlm.nih.gov/37286459/

Read the paper for more considerations and recommendations
nature.com/articles/s41...

Expressing as change from baseline can improve efficiency and area under the curve is a useful summary statistic

See the tables attached for some recommendations on blood sampling dependent on the analyte of interest

What about analysis?

Timing makes a difference to the inferences drawn (also dependent on the analyte of interest, so what about some recommendations?

Depending on the analyte of interest, it may be relevant to consider where blood is sampled from (fingertip capillary, a vein, or an artery)

Note that this will affect the concentrations measured (see figure), depending on net uptake/release by tissues

What about sample timing?

There are various ways of presenting these with different strengths and limitations

What about blood sampling?

Generally these questionnaires ask at least 4 key questions relating to:

Hunger
Fullness
Prospective food consumption
Satiety

How do these get analysed into useful outcomes?...

Mixed-meal tolerance test (MMTT) typically involves ingestion of a meal containing carbohydrate, fat and protein (🍝🧈🍗)

Blood samples and questionnaires are performed before and after ingestion of the meal

What do these questionnaires measure?...

The mixed-meal tolerance test in appetite research
🧵

Topics covered:
-Familiarisation/Standardisation 🟰
-Meal stimulus 🥣
-Appetite scales 😋
-Blood sampling 💉
-Blood analyses 🩸
-Data handling 📊
nature.com/articles/s41...

After very valuable comments from referees, here's the revised preprint for our paper "Understanding treatment response heterogeneity using randomised crossover trials: A primer for exercise and nutrition scientists" (@lorenzololli.bsky.social @j-t-gonzalez.bsky.social et al) osf.io/preprints/os...

Here is a link to the trial I refer to. The energy expenditure outcome was one of several outcomes. Not all showed such unreliable response heterogeneity. The crucial estimand is the person-by-treatment interaction variance, not what is seen on a waterfall plot link.springer.com/article/10.1...

No agreement at all. What we are dealing here is within-subjects (period-to-period) random variation swamping any response heterogeneity. Without a replicate trial, we wouldn't have known that 1st set of responses are not "true". Unfortunately, many conclusions on this topic are compromised by this.

Looks good doesn't it? This is how some researchers conclude there are individual differences in response. Some might even say participant 1 is an "extreme responder". But just to say that this trial was actually a replicate crossover. Here's the second set of differences plotted in the same order.

Waterfall plots present changes or differences for individual cases. While "show the data" is 👍, just a reminder that these plots don't inform about treatment response heterogeneity on their own. Here's a plot of the treatment-control differences in energy expenditure from a crossover trial.

New PhD opportunity in nutrition and metabolism at @uniofbath.bsky.social - closing date 31st March. Come and join CNEM! eur01.safelinks.protection.outlook.com?url=https%3A...