Muscle Matters When It Comes To Ozempic

In our recent Fuelin Sessions Podcast episode (1), Jan Frodeno and I discussed this research article (2). It is a commentary authored by several prominent researchers on the impact of medically induced weight loss and skeletal muscle. Some interesting statistics are raised and this is what I wanted to dive into.

SOME INTERESTING STATS

The authors highlight significant differences in muscle loss when comparing traditional caloric deficit weight loss to the medically induced (GLP-1) weight loss method. See infographic below.

This large difference in loss of fat-free mass (FFM) is hypothesised as being the result of rapid weight loss rather than the independent effect of the medication. It should be cautioned that this is a hypothesis and at this stage it is unknown. More research is required. to understand what the mechanisms of loss of fat-free mass might be. When comparing the average loss of muscle per year based on 8% loss per decade, it is a mere 0.8%. Given some of the early data related to GLP-1 and muscle loss, you begin to see the potential downsides.

DEFINITIONS THAT CAUSE CONFUSION

A word of caution with regards to these figures is the definition of fat free ass vs lean body mass. Fat Free Mass (FFM) is defined as bone + skeletal muscle + connective tissue + organs + water. Lean Body Mass (LBM) is defined as skeletal muscle mass + connective tissue + organs + water. Lean Muscle Mass (LMM) is defined as skeletal muscle mass. It is not uncommon for some authors to use FFM interchangeably with LBM & LMM yet they are quite distinct and should not be confused. As such, the numbers being discussed are potentially over-blown. In terms of fat-mass (FM) lost as a result of GLP-1 agonists, the percentage compared to FFM or LBM is often reported as 2-3 x more than LBM or FFM lost. This would indicate that even with significant loss of lean body or lean mass that some health benefit should be achieved via loss of significant fat mass. There is no doubt that fat mass loss is significant with GLP-1 medications. The question yet to be answered definitely is how much lean mass is bing lost as well?

MUSCLE AND ITS IMPORTANCE

As you can see in the infographic below, muscle plays an important role in structure and metabolism. THe loss of muscle will therefore impact both these important roles. Interestingly, some data suggests that loss of muscle mass does not always impact muscle strength. This is limited and relates to studies performed on bariatric and metabolic surgeries. (2) This may be limited to the population studied and not be applicable to everyone. The authors do a fantastic job highlighting the role muscle plays in metabolism, exercise physiology and immune function. Too often, we become myocentric and focus solely on strength & function whilst forgetting the other important roles that muscle plays.

Figure: Selected key roles of skeletal muscle as a structural versus metabolic organ.
Credit: Julia Montenegro and Leticia Ramos da Silva

SCARY THOUGHTS

As I have highlighted several times before (here and here), loss of muscle mass can occur at anytime and especially as we age. If these new drugs result in significant loss of LBM, LMM or FFM even with large fat mass loss it could be problematic to the long term health of the individual. the reason for this is that the ability to regain lean mass becomes harder as we age. The authors highlight that often users of these drugs eventually stop using them and unless the lifestyle issues that resulted in the initial fat gain are addressed, that the weight is likely to be regained. The weight regained will be fat mass, not muscle mass. And thus, the cyclic nature of weight loss then weight gain then weight loss occurs with a progressively, rapid loss of lean mass underneath it all. Scary to visualise. Sarcopenic Obesity on steroids is one way to think about it!!

STEPS TO OFFSET THE LOSS

As I mentioned in the podcast, if I was advising someone on GLP-1 then I would certainly look to address and in still some key components to their plan. These would include and not limited to;

High protein intake 1.8-3g/kg/BW
Periodised carbohydrate and fat intake
Fruit & vegetables daily
Resistance training 3-4x/week - hypertrophy focus
Potential use of Blood Flow Restriction (BFR)
No fasted training
Minimal cardio outside of walking

There have not been any studies investigating methods to offset LMM/FFM/LBM loss. Hopefully they will come out soon. I am sure they will as GLP-1s are not going away anytime soon. The more information and research we have on these drugs an the impact on weight loss (both fat and lean mass) the better.

REFERENCES:

1. FUELIN SESSIONS EPISODE 2: (https://open.spotify.com/episode/5XpuHsUf2ck6JWCOSpGcLo?si=vclI5jq6SrW6DlSPyvU2lA)

2. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00272-9/abstract

3. Jung HN, Kim S-O, Jung CH, Lee WJ, Kim MJ, Cho YK. Preserved muscle strength despite muscle mass loss after bariatric metabolic surgery: a systematic review and meta-analysis. Obes Surg 2023; 33: 3422–30

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SCOTT TINDAL
October 2, 2024
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