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What fraction of loss on oral semaglutide is lean mass according to SOUL?

Asked 28 Aug 2024Modified 20 months agoViewed 20k times
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The particulars: oral semaglutide · SOUL.

I want to understand what this actually establishes, as opposed to what it is being used to imply.

My concern is that I am being invited to draw a conclusion the data does not support.

What does this actually establish, and what does it not?

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JF
askedjuliette_farnese12k2828 Aug 2024
8Note that the label instructions differ between agents on precisely this point. – k_szabo 9 months ago
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2 Answers

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The commonly quoted figures for lean-mass loss are mostly measurement artefacts, and the artefact is well understood: fat-free mass as measured includes water and glycogen, both of which fall early and neither of which is contractile tissue.

Hydration state moves a DEXA lean-mass figure directly, because the algorithm assigns water to the lean compartment. Scanning fasted, at the same time of day, before training and without a recent high-carbohydrate day is the difference between a comparable sequence and a noisy one. Bioelectrical impedance is far more sensitive to hydration again, which is why its trend is unusable at this timescale.

What each body-composition method measures

MethodMeasuresSensitive toLeast significant change
DEXAThree-compartment by attenuationHydration, positioning~2–3 % regional lean
BIA (consumer)Impedance, modelledHydration, food, temperatureNot usable at this timescale
Air displacementTwo-compartment by densityLung volume, hair, clothing~1–2 % fat mass
Tape and scaleCircumference, massTechniqueSurprisingly usable as a trend

On the detail: DEXA precision is better than people assume for fat mass and worse than people assume for lean mass in a single scan — the least significant change for regional lean mass on a well-maintained scanner is on the order of a few per cent. That means two scans three months apart can differ without anything having happened, and it means a scan sequence needs to be at least three points before a trend is interpretable.

Worth stating that a DEXA sequence is only as good as its protocol consistency, and most people’s sequences are not consistent enough to support the conclusions drawn from them.

Train, eat the protein, measure something functional, and give the trend three months before you interpret it.

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DV
answeredDr_Bram_Verhoeven85k24810 Dec 2024
The placebo-arm figure is the part everyone omits. – tamsin_wray 5 months ago
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On the detail: what the data supports is narrower than what gets recommended, so it is worth separating the two.

Protein target, worked: at 88 kg, a target of 1.6 g/kg is 88 × 1.6 = 141 g per day. Spread across three eating occasions that is roughly 47 g each, and the leucine threshold for a maximal muscle protein synthetic response is met at around 2.5 to 3 g of leucine, which corresponds to roughly 30 to 40 g of a high-quality protein. So three meals at 40 g plus one 25 g snack gets you to 145 g and clears the per-meal threshold each time. On 900 kcal that leaves about 340 kcal for everything else, which is the actual constraint.

Absolute strength holds up better than scale weight during a deficit for a straightforward reason: strength is substantially neural and skill-based, and the contractile tissue you retain is being trained harder relative to its size. Grip strength and repetition maxima are therefore lagging indicators of muscle loss rather than leading ones, which is an argument for measuring both.

The body-composition substudies in the major programmes consistently report that the proportion of weight lost as fat mass is approximately three quarters or better, with the lean-mass fraction falling within the range seen in dietary weight loss of comparable magnitude[1].

Measure strength as well as mass. It is cheaper, it is less noisy, and it is closer to what you actually care about.

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DW
answeredDr_Elias_Weiss46k3829 Nov 2024
2Two of us worked through this independently and arrived here, so it is at least reproducible. – tandem_gradient 36 days ago
Worth adding that the method section is where the answer usually is. – n_takahashi 9 months ago
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