PeptideStack
5.2kquestions
20kanswers
220users

What fraction of loss on survodutide is lean mass according to STEP 3?

Asked 10 Jun 2024Modified 23 months agoViewed 22k times
2

Conditions: survodutide · STEP 3.

I would like to know the limits of what can be inferred from this.

What I am trying to avoid is over-reading a single result, which I have done before.

What can I legitimately conclude from this figure?

lean-mass
lean-mass

Lean body mass as measured rather than assumed: what DEXA, BIA and air-displacement plethysmography each actually estimate, the body-composition…

164 questions
muscle-loss
muscle-loss

Loss of contractile tissue during energy deficit: what fraction of total loss is lean mass, why the commonly quoted figures are measurement…

82 questions
dexa
dexa

Dual-energy X-ray absorptiometry: what it measures, its precision limits, why hydration state and scan positioning move the numbers, and how to…

84 questions
shareeditfollowflag
NK
askednils_karlberg13k1710 Jun 2024
8I tested this on two lots and got the same answer, so at least it reproduces. – unit_math 4 months ago
The timing signature is the useful part. Everything else is confounded. – micron22 6 months ago
add a comment

5 Answers

Accepted answer first, then by votes
61

Accepted answer

Start with the arithmetic, because the answer to the practical question is usually a number and the number is usually achievable.

Food noise returning is not obviously tolerance. Receptor desensitisation is one hypothesis; a second is that the initial effect was partly novelty and partly the steep early deficit, and a third is that intake has drifted upward and the signal is being outcompeted rather than weakened. The three make different predictions about what a dose increase would do.

The first four weeks of loss is substantially fluid and glycogen. Each gram of stored glycogen carries roughly three grams of water, and total glycogen is on the order of 400 to 500 g, so the obligatory water shift alone accounts for a couple of kilograms. This is why the first month looks dramatic and the second looks like a plateau when in fact the fat-loss rate has not changed.

The STEP 1 extension reported substantial regain in the year after treatment withdrawal, with weight and cardiometabolic variables trending back toward baseline[1].

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.

A maintenance plan written before you need it is worth more than a better loss plan.

shareimprove this answerflag
NN
answered · acceptednine_point_nine45k13820 Jun 2024
Sponsored

Sigma-Aldrich - Certified Reference Materials

Analytical standards and reagents with traceable certificates. Every quantitative result you read inherits the accuracy of the standard behind it.

Shop standards
73

The mechanism is worth having straight, because it predicts which interventions can work and which cannot.

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.

Cardio does not interfere with lean-mass retention at the volumes anyone here is doing; the interference effect in the literature appears at high concurrent volumes in trained athletes. What cardio does at a large deficit is add to the deficit, which is either the point or a problem depending on the objective.

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].

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

shareimprove this answerflag
DR
answeredDr_Priya_Raghunathan94k24812 Jul 2024
8Have you seen anything published on this, or is it inference from the mechanism? – ilaria_bertone 4 months ago
7Useful. I have added the accept threshold suggestion to my own notes. – seven_day_half 2 months ago
add a comment
48

The distinction that resolves this is between proportional loss and functional loss. Losing lean mass in proportion to total mass is what happens in every weight loss intervention. Losing function is not, and function is measurable.

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.

Concretely, 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.

The plateau is arithmetic. Treat it as arithmetic and the response follows.

shareimprove this answerflag
DK
answereddermot_kiely14k1723 Jul 2024
2Good answer, but the confidence interval in the cited trial is wider than implied. – grainne_ahearn 3 months ago
add a comment
28

What the data supports is narrower than what gets recommended, so it is worth separating the two.

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.

Adaptive thermogenesis — a fall in energy expenditure beyond that predicted by the change in body composition — is documented across weight-loss interventions and is the mechanistic basis for the plateau being expected rather than anomalous.

I would be careful with the supplement literature here; effect sizes are small, the studies are mostly in trained young men, and generalisation to a large deficit is not obviously valid.

Two resistance sessions a week and a protein target you actually hit will do more than any refinement beyond them.

edited 6 Jul 2024 by plate_count_9k — clarified the distinction between purity and content

shareimprove this answerflag
P9
answeredplate_count_9k95k1581 Jul 2024
23

A plateau at four to six months is the expected shape of the curve, not a failure of it. Energy expenditure falls with mass, and the deficit closes itself unless intake falls further.

Fibre at very low total intake is a trap. Soluble fibre needs water and motility to work; insoluble fibre adds bulk to a slow transit. At 900 kcal a day with delayed gastric emptying, an osmotic agent is more predictable than a bulking one, and adequate fluid is doing more work than either.

SURMOUNT-4 provides the cleanest maintenance-versus-withdrawal contrast available in the class, and it is the reference for any claim about what happens after stopping[1].

One qualification: none of this is a clinical assessment, and unexplained loss of function rather than of mass is a reason to see someone rather than to adjust a programme.

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

shareimprove this answerflag
FC
answeredforty_two_c43k3826 Aug 2024

Your answer

Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.

Not medical advice. Research-use-only compounds are not approved for human use.