Everyone is About to Become Lean and Muscly (new evidence) — Transcript

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1. 0:00In 2024, a baby was born in Germany who
2. 0:02by any measure was impossible. He was
3. 0:04only a few days old and he already had
4. 0:06visible muscles. His thighs and upper
5. 0:08arms looked like a tiny bodybuilder.
6. 0:11Doctors checked him for every disease
7. 0:12that could explain it and they found
8. 0:14nothing wrong. He wasn't sick. He was
9. 0:16just extraordinarily, effortlessly
10. 0:18strong. And when they looked at his
11. 0:20genes, they found the answer. He'd been
12. 0:22born with both copies of a single gene
13. 0:24switched off. A gene that makes a
14. 0:26protein called myostatin and myostatin,
15. 0:29it turns out, has one job in your body
16. 0:31to put the brakes on muscle growth. It's
17. 0:33one of the reasons why you don't just
18. 0:35keep adding on muscle forever. The
19. 0:36baby's brakes were just gone and
20. 0:38scientists that only found the myostatin
21. 0:40gene about 7 years earlier in 1997. And
22. 0:44the moment they understood what it did,
23. 0:45the implications were staggering. If you
24. 0:47could switch off the myostatin gene in
25. 0:49anyone on purpose, you might be able to
26. 0:52beat diseases that waste muscle away
27. 0:54like muscular dystrophy or even
28. 0:56sarcopenia. There was just one problem.
29. 0:58For nearly 30 years, nobody could switch
30. 1:00off the myostatin gene safely. But the
31. 1:03breakthrough, which has only just been
32. 1:04published, arrived in time to address a
33. 1:06growing problem that didn't even exist
34. 1:08in 1997. The problem is an unintended
35. 1:11consequence of what's happened to weight
36. 1:13loss over the past few years. So we have
37. 1:15become incredibly, astonishingly good at
38. 1:18melting fat away. So a decade ago, the
39. 1:20best drugs took about 8% of your body
40. 1:22weight off and with the burden of daily
41. 1:24injections, most people just gave up.
42. 1:26But then came semaglutide or Ozempic
43. 1:29that increased weight loss to around %
44. 1:32then to zepbound pushed it past 20% and
45. 1:34the newest one in the line, a triple
46. 1:36agonist drug called retatrutide, it took
47. 1:38people down by 28% of their body weight
48. 1:41loss in a big recent trial. So for
49. 1:43someone starting at about 110 kg, that's
50. 1:46more than 30 kg gone from a weekly
51. 1:49injection. That's bariatric surgery
52. 1:51territory, of course, without the
53. 1:52surgery. But here's the catch and it's
54. 1:54all over the internet right now. When
55. 1:56you lose that much weight, some of what
56. 1:58you lose is not fat. It's muscle, and
57. 2:00you've probably seen what that can look
58. 2:02like. If someone drops a huge amount of
59. 2:04weight, they end up looking smaller, but
60. 2:05they can also look a bit hollowed out
61. 2:07and gaunt. So, some people started to
62. 2:09panic that these drugs were melting
63. 2:10people's muscle away. But, we do need
64. 2:12some critical context here because the
65. 2:14truth is far more boring and reassuring
66. 2:16than the panic. So, when researchers
67. 2:18pulled 22 trials of these drugs and
68. 2:20added up exactly where that weight loss
69. 2:22actually came from, about a quarter of
70. 2:24it was muscle, and three quarters of it
71. 2:26was fat. But, here's what most people
72. 2:28miss. That 25% lean mass loss is not
73. 2:31unique to Ozempic or other GLP-1
74. 2:33medications. A quarter is roughly what
75. 2:35you'd lose when you diet the
76. 2:37old-fashioned way. It's roughly what you
77. 2:39lose after weight loss surgery. Doctors
78. 2:41have a decades-old rule of thumb that
79. 2:42about a quarter of any weight that you
80. 2:44lose is in lean tissue. Now, we can
81. 2:47counteract some of this muscle mass loss
82. 2:49by a good protein diet and regular
83. 2:50resistance exercise. But, the dream
84. 2:52result is that we only want to lose fat
85. 2:55mass, not lean mass. We want to protect
86. 2:57our muscles during this weight loss
87. 2:58journey, and the key to that holy grail
88. 3:00of losing fat and not muscle brings us
89. 3:03to myostatin. In 1997, researchers bred
90. 3:06mice with the myostatin gene deleted,
91. 3:08and the mice, they grew enormous. They
92. 3:09look exactly like the double-muscled
93. 3:12cattle that farmers had bred for
94. 3:13centuries. They were bulging, blocky,
95. 3:15with twice the muscles of a normal mouse
96. 3:17from a single gene switched off. So, the
97. 3:20dream here is obvious. If turning off
98. 3:22the myostatin gene doubles muscle mass
99. 3:24in a mouse, then a drug that turns it
100. 3:26off in a person could rebuild the wasted
101. 3:29muscles of dystrophy or of old age. And
102. 3:32then in 2004, proof that it might be
103. 3:34safe in humans came from that German
104. 3:36baby. It was an example of a natural
105. 3:38human myostatin knockout walking around
106. 3:41who was extraordinarily strong and
107. 3:43completely healthy. If we managed to
108. 3:44turn this gene off, it seemed, then
109. 3:46nothing appeared to break. So, the
110. 3:48target was obvious, and the safety
111. 3:49looked reassuring, and the prize was
112. 3:52enormous. And then for nearly 30 years,
113. 3:54almost everyone who tried to hit this
114. 3:56target failed. But why? Well, the tool
115. 3:58that you'd use is a monoclonal antibody.
116. 4:01Think of it like a guided missile that
117. 4:03scientists designed to lock in onto one
118. 4:04specific molecule shape and then
119. 4:06neutralize it. The problem is that when
120. 4:08myostatin is switched on, it looks
121. 4:10almost identical to a whole family of
122. 4:12related proteins that your body needs
123. 4:14for other jobs. So, the missile aimed at
124. 4:16active myostatin, it tends to hit its
125. 4:19other cousins, too. And that's when you
126. 4:20get side effects, or you blunt things
127. 4:22that you never meant to touch. So, after
128. 4:24decades of attempts, the verdict in the
129. 4:26field became almost a punchline. Great
130. 4:28expectations, but with limited success.
131. 4:30So, the breakthrough was about being
132. 4:31more precise. So, the newest drug,
133. 4:34called apitegromab, it doesn't go after
134. 4:36active myostatin, where all the
135. 4:38look-alike cousins are. Instead, it
136. 4:40grabs the myostatin earlier in its
137. 4:42inactive, folded-up precursor form,
138. 4:44before it's ever switched on. And that
139. 4:46precursor shape is far more unique.
140. 4:48Nothing else in the family looks quite
141. 4:50like it. So, the missile finally locks
142. 4:52on to myostatin and only myostatin, and
143. 4:55it leaves everything else alone. That
144. 4:57selectivity, as in hitting one target
145. 4:59cleanly, is the exact thing that 30
146. 5:01years of attempts have been missing. And
147. 5:03before anyone ever pointed the strike at
148. 5:05weight loss, it earned its stripes
149. 5:07somewhere far more demanding.
150. 5:09Apitegromab, it was first tested in
151. 5:11spinal muscular atrophy, a brutal
152. 5:13genetic disease that destroys muscles of
153. 5:15children. In trials there, it improved
154. 5:18motor function in kids who were losing
155. 5:19it. And it did so safely. So, the tool
156. 5:22had finally matured. We finally had a
157. 5:24clean, selective, human-proven way to
158. 5:26take the break off muscle formation. And
159. 5:29it matured at the exact moment that the
160. 5:30world handed it a brand new use. Because
161. 5:33just as apitegromab was proving itself,
162. 5:35the new weight loss drugs, they were
163. 5:36driving fat loss faster than medicine
164. 5:39had ever seen. So, does this approach
165. 5:41work by combining GLP-1 medications, or
166. 5:43the weight loss medications, with
167. 5:45myostatin inhibitors? Well, yes, but
168. 5:47there are problems. So, there were two
169. 5:49medications that were leading the race
170. 5:51to apply this breakthrough in muscle
171. 5:53preservation to the problem of muscle
172. 5:55loss during weight loss. So, they
173. 5:56represent two completely different
174. 5:58philosophies on how aggressive you
175. 5:59should be. So, the first one we've
176. 6:01already talked about, a pigaveramab,
177. 6:03it's the clean one. It does exactly what
178. 6:05we just described. It selectively blocks
179. 6:07myostatin, but it's bimagrumab that's
180. 6:10the showstopper. And instead of just
181. 6:11blocking myostatin, it blocks a broader
182. 6:14docking port, the active receptor, which
183. 6:16is a much heavier hand on the whole
184. 6:18system. And on its own, it does
185. 6:19something that no diet drug does. So,
186. 6:21people's muscles actually grew as their
187. 6:24fat fell, though the total weight loss
188. 6:26was modest. So, if you bolt it onto
189. 6:27semaglutide, you get the headline
190. 6:29number, substantial weight loss, about
191. 6:3192% of it from fat, with muscle largely
192. 6:34protected. So, the muscle mass loss is
193. 6:36much smaller here compared to
194. 6:38semaglutide alone. And it's genuinely
195. 6:40the closest thing that anyone has made
196. 6:42to the lean and ripped from a vial. But
197. 6:44that power comes with serious downsides.
198. 6:46Most people on bimagrumab, they got
199. 6:48muscle spasms. About a third of them got
200. 6:50acne, and more seriously, it pushed up
201. 6:53their LDL cholesterol, the kind that can
202. 6:55build up in blood vessels, by as much as
203. 6:5717%. So, that is the wrong direction for
204. 7:00your heart. And then quietly, in
205. 7:01September 2025, the company developing
206. 7:04one of the big bimagrumab combinations
207. 7:07paused their program because of these
208. 7:08safety signals. All of this creates a
209. 7:10lingering worry that if we start using
210. 7:12these drugs to protect our muscles,
211. 7:14maybe they start creating problems with
212. 7:16our hearts. But if you can push gently,
213. 7:18maybe that's when you can spare the
214. 7:20muscles cleanly and not have any of
215. 7:22these side effects, which is exactly why
216. 7:24the gentle clean drugs, or the a
217. 7:25pigaveramab, matters so much. The whole
218. 7:28bit is that you can protect your muscles
219. 7:30without poking the heart. So, does it
220. 7:32work? Well, this is the trial that
221. 7:33inspired this video. It's called
222. 7:35Embrace, and the design is beautifully
223. 7:38simple. So, they took 102 adults with
224. 7:40obesity, and every single one of them
225. 7:42were put onto Zepbound, and then they
226. 7:44split them into two groups. So, one half
227. 7:46also got the apitegromab, the muscle
228. 7:48protector, and the other half got a
229. 7:50dummy infusion on top. Neither patients
230. 7:52nor the doctors knew who got which.
231. 7:54After 6 months, they measured everyone
232. 7:56and measured precisely how much of the
233. 7:58weight that was lost was from fat and
234. 8:00how much was from lean mass. And the
235. 8:02combination appeared to work. So, the
236. 8:04group on the apitegromab, they lost
237. 8:06about half as much lean mass compared to
238. 8:09the placebo group. Both groups lost
239. 8:11about the same amount of weight, but in
240. 8:12the apitegromab group, a far bigger
241. 8:14share of that weight was fat, about 85%
242. 8:17fat versus 70% in the placebo group. So,
243. 8:20this gives us the first hint that we
244. 8:22might hit the holy grail in the future
245. 8:24where we can lose fat mass and also
246. 8:26protect our lean mass, where we can get
247. 8:28the best of both worlds and do it
248. 8:30safely. But, we also need to be clear
249. 8:31about what the study found because
250. 8:33there's a key result that the headlines
251. 8:35skipped. So, the apitegromab group, they
252. 8:37were not measurably stronger. The trial
253. 8:39tested it directly. So, they used grip
254. 8:41strength and how easily people could
255. 8:43stand up and then sit back down in a
256. 8:44chair. So, on both measures, the muscle
257. 8:47protected group were no better than the
258. 8:49dummy injection group. The drug kept the
259. 8:51muscle on the scan, but that extra
260. 8:52muscle, it didn't let people do anything
261. 8:54more with their bodies. And those are
262. 8:56two different things. Keeping lean mass
263. 8:58that shows up on a scan is the means,
264. 9:00but being stronger and more capable and
265. 9:02less frail, that's actually the goal.
266. 9:04And only the first one was proven here.
267. 9:06Instead, this trial represents again
268. 9:07where the future is potentially headed
269. 9:09where we can all be a healthy weight and
270. 9:11still have strong muscles no matter our
271. 9:13age, but more work is needed. And a few
272. 9:16blunt words on what the internet will
273. 9:17try and sell you here. So, if you search
274. 9:19how to keep muscle on Ozempic, you'll
275. 9:21likely fall into a world of gray market
276. 9:23scams and muscle peptides with names
277. 9:26like YK11 for protecting muscle during
278. 9:28weight loss. These essentially have no
279. 9:30proper human evidence in the form of
280. 9:32well-designed and conducted randomized
281. 9:34controlled trials. What they have
282. 9:35instead is a real track record of liver
283. 9:37damage and even worse. So, in my
284. 9:39opinion, they're not worth your money
285. 9:41and not worth your liver's health.
286. 9:42Instead, here's what to actually do
287. 9:44about muscle loss while you're on GLP-1
288. 9:46medications today. So, the thing that
289. 9:48works right now with no prescription and
290. 9:50no risk is the unglamorous one,
291. 9:52resistance training a couple of times a
292. 9:54week and enough protein in your diet.
293. 9:56That is the part that you can control
294. 9:58and it already works. For me personally,
295. 10:00I take 1.25 mg of tirzepatide a week
296. 10:03myself and I protect my muscles by doing
297. 10:05exactly this, by doing resistance
298. 10:07exercise and eating enough protein. And
299. 10:09one supplement worth considering is
300. 10:11creatine. It's the most studied
301. 10:12ingredient there is for muscle and
302. 10:14strength. And one last thing, I just
303. 10:16mentioned that I take tirzepatide, not
304. 10:18the newer and more powerful retatrutide.
305. 10:20And there's a very good reason for this.
306. 10:22And there's also a good reason why I
307. 10:23take one of these medications even
308. 10:25though I'm lean and non-diabetic. So,
309. 10:27make sure to check out this next video
310. 10:29here where I lay out all of my
311. 10:30reasoning.