Looksmaxxing, Peptides and GLP-1s: A Conversation with Dr. Noc on Chasing Perfection

The conversation opens with the question of what peptides are. Dr. Noc describes them as closely related to proteins and as substances the body produces itself. They have important signalling and hormonal functions, and GLP-1 is one example.

To illustrate the effect of GLP-1 drugs, the discussion turns to a user who describes his experience. He says his body fat percentage drops while his muscle mass goes up. When asked whether he takes a peptide, the answer given is that whenever even a small amount of body fat is lost, visceral fat is broken down first, and GLP-1 reduces visceral fat naturally while total body fat falls.

Asked about the effect of these drugs on people who are not diabetic, and on culture more broadly, Dr. Noc describes two aspects: a cultural one and a medical one. He says peptide drugs fall into a medically revolutionary category, with insulin as an earlier example of a peptide in that role.

He says he considers them a medical revolution that will prevent a huge number of chronic diseases that could never have been prevented through lifestyle changes alone. He acknowledges that good sleep, movement and proper nutrition are known to matter, but says that in practice these have been very hard for many people to sustain for decades, even when they know what to do.

The discussion also touches on how the cultural meaning of weight loss is changing. The conversation notes that people increasingly want a pill or an injection rather than six months in a gym, and that GLP-1 drugs are the closest thing to that option.

Discussion turns to whether the drugs might carry unknown downsides. The guest says the medication has not been around long enough to know what effects it will have as people age. He notes that these drugs can produce weight loss in the range of roughly 10 to 20 percent, depending on starting point and dose.

He then describes the risks of excess body weight, which is linked to a long list of diseases, including dementia. He says cardiometabolic health influenced by visceral fat affects the risk of brain disease as well as heart disease. Based on this, he says it is likely that GLP-1 treatment will reduce the risk of many chronic diseases associated with long-term excess weight.

Asked whether people should wait, he says that we do not know what will happen in 20 or 30 years, but questions whether that is a sufficient reason to wait that long before starting, given the concrete benefits available now.

Dr. Noc suggests that the market for unproven weight-loss supplement bottles may have shrunk since GLP-1 drugs arrived. He says he has noticed less interest in products sold without efficacy figures, since these drugs have clear clinical data on both benefit and risk.

Asked whether people now believe science or demand more of it, he says there comes a point where science reaches a level it can no longer be ignored. Chuck Nice counters that people underestimate how foolish humanity can be, and the discussion returns to the role of personal anecdote.

Dr. Noc agrees that people see results themselves. Everyone has a friend, he says, who has lost weight, and seeing that friend's visible change is part of why people believe the treatment works.

Returning to the question of how to deal with visceral fat, Dr. Noc says that it is one of the special cases where biology works in our favour. When a person loses a little weight, visceral fat is broken down disproportionately first, which matters because it is linked to future cardiometabolic health risk.

He cites a UK Biobank study comparing overweight people who look at the scale with normal-weight people carrying a lot of visceral fat, since one can be overweight on the scale yet have little visceral fat. Normal-weight people with much visceral fat had about a 6 percent risk of developing type 2 diabetes, while overweight people with little visceral fat had about 2 percent, a threefold difference in the opposite direction from what one might expect from appearance.

He adds that visceral fat can be reduced through aerobic activity without necessarily changing the number on the scale, though the activity needs to be substantial, with a threshold around 150 minutes per week.

Dr. Noc describes a peptide as a chain of amino acids, larger than a single amino acid but smaller than a full protein. He also notes that oral semaglutide has a bioavailability of about 2 percent, far lower than the figures for injection, which is why many people prefer injection.

Asked about people who want to avoid the effort of exercise, the discussion acknowledges the joke that the lazy person is the one using peptides. Dr. Noc responds that the boring basics still apply: sleep, proper nutrition, strength training and aerobic activity. The conversation then moves to creatine as a supplement that can support strength training.

On creatine, the guest says the body produces about one gram per day and an omnivore takes in roughly another gram through food, while a typical supplementation dose for strength training is about 5 grams per day, which he describes as a small amount of the powder.

Turning to stacking, Dr. Noc describes taking several peptides at once as very popular, but says he is not sure it works. He contrasts the GLP-1 drugs, which went through large clinical trials with thousands of people and gave clear information on benefits and risks, with peptides such as BPC-157 and TB-500, for which there are very few or in some cases no human clinical data.

He identifies the peptides discussed in the stack popularly called the Wolverine stack as being promoted on limited evidence, mostly from animal studies. He notes that many treatments that worked in animal models of disease did not carry over to humans, and cites a statistic that roughly 10 percent of medicines entering human clinical trials reach the market, with about 5 percent for cancer drugs.

He also refers to the 2006 TGN1412 trial, in which a dose scaled from primate data caused severe inflammatory reactions in the first human volunteers, with organ failure developing and one volunteer losing fingers. He explains that the relevant T-cell marker differed between primates and humans, so the animal model had missed the risk.

He adds that unregulated peptides may be made without sterile conditions, which could introduce inflammatory contaminants, and that obtaining them through regulated pharmacies reduces that risk.

Dr. Noc says that a peptide with strong biological activity, including the ability to build new blood vessels, may carry risks as well as benefits. He notes that this could in principle feed the growth of a tumour that is already well vascularised, although he stresses that this does not mean the peptide causes cancer or worsens the course of cancer in patients who take it.

He says he would not rule out a definite risk. He argues that the potential benefits and risks should be weighed carefully in clinical studies before anyone accepts lists of good and bad peptides.

He also warns about products bought from grey-market sources. Even when a product is a genuine GLP-1 drug such as retatrutide, tirzepatide or semaglutide, it may be cheaper through such channels, but he is not fully certain that the contents of the vial match what is claimed.

Dr. Noc describes peptides as a kind of transition point between an amino acid and a complete protein, and explains that much of what happens in the body depends on how proteins fold and behave. He mentions that the AlphaFold system received a Nobel Prize for applying AI to the protein folding problem.

Neil deGrasse Tyson asks whether this means the future of health will be a few brilliant people in labs working out how to assemble these pieces. Dr. Noc responds that he would be surprised if medicine did not keep getting better, and that it would surprise him if these were the last approved peptide drugs.

He notes that around 80 peptide drugs are approved by the FDA and that more are likely to follow, probably designed with in silico methods and massive AI. In silico development, he explains, means screening a very large number of compounds, often from microbes and soil, and then modifying the promising hits to improve effectiveness or safety.

Discussing ageing, Dr. Noc says that from age 30 a person can expect to lose roughly 3 to 8 percent of muscle mass per decade, while cardiorespiratory fitness declines and bone density falls, especially in women after menopause. The conversation touches on the cultural pressure to look young and the sense that ageing is undervalued.

He says these trends cannot be escaped: muscle mass, bone density and cardiorespiratory fitness will not rise between ages 30 and 80. But the slope of that change can be strongly influenced, so the focus of his videos is not only on people in their fifties to eighties but also on people from age 30.

He describes VO2max as the total amount of oxygen a person can use at maximum effort, which he likens to the size of an engine. A higher VO2max means better cardiorespiratory fitness and general health, and it is one of the things he says can be improved through training.

Dr. Noc explains that when someone has genuinely low testosterone, raising it to a normal level can help some sexual symptoms, may slightly improve mood, and can improve bone density. He says that much of what people hear, or wish for, will not inflate them by raising testosterone to a normal level.

He distinguishes this from testosterone-steroid cycles used by bodybuilders, which go far beyond replacement dosing and carry much larger risks, including roid rage.

The conversation then turns to ageing as a matter of appearance. Dr. Noc notes that people focus on the face and skin rather than abdominal fat, and mentions an advertising psychologist's finding that people over 30 become much less decided about brand purchases with each passing year, so advertisers spend heavily on younger consumers.

Dr. Noc says that the spread of dementia is shaped by a long list of statistical risk factors, and that dementia can still occur even when all of them are managed perfectly. He nevertheless argues that the idea that it is entirely up to fate is wrong, because there are things a person can do to change their risk.

He groups the factors into three areas. The first is cardiometabolic, including blood lipids, blood pressure and blood sugar, which matter because the brain is highly vascularised. The second is environmental, including air pollution, which is linked to later brain disease. The third is social, where correcting hearing loss reduces the risk of progression, since hearing loss can lead to withdrawal.

He also says heredity plays a role, and that together these factors account for much of total dementia risk.

Dr. Noc says creatine has clear evidence for improving strength training and increasing muscle mass by 10 to 20 percent. Its cognitive benefits, by contrast, are much less established: the studies are small, heterogeneous and often uncontrolled.

He describes one widely discussed study involving 20 Alzheimer's patients who received creatine, which had no placebo group. The authors themselves noted that the reported improvements may reflect practice effects from repeated cognitive testing rather than the supplement.

He says the biggest risk for him is that people will think they only need to take a spoonful or two of creatine, and will rely on it instead of the other measures that are proven to reduce risk. He also expects that GLP-1 drugs, by improving cardiometabolic risk factors, are likely to reduce future brain disease, though he says this will take a long time to confirm.

Dr. Noc explains that NAD, or nicotinamide adenine dinucleotide, carries electrons in cellular energy metabolism, much as in the burning of sugar, and that it is broken down by sirtuins, enzymes linked to DNA repair, inflammation and stress.

Cohort studies show that NAD levels fall over time, and nicotinamide supplements can measurably raise them. However, he says it has not been shown that raising these levels improves outcomes in any meaningful way, except in one specific case.

That case involves people at high risk of skin cancer. In that trial, participants had had two skin cancers in the previous five years, so the group is not representative of the general public taking these supplements. It showed about a 20 to 25 percent relative reduction in the risk of another skin cancer diagnosis, which he contrasts with social media claims that levels simply decline with age.

Asked about the obsession with looking young and the possibility of looking old or unattractive, Neil deGrasse Tyson says he focuses on things he can control: strength training, aerobic exercise, nutrition and better sleep. He says his sleep has improved, and that he now sleeps about 45 minutes more per night than last year.

He says the concern for him is losing muscle mass, bone density and cardiometabolic fitness as he ages, and that he feels better when he improves these things. He says the goal is to spend more time with his daughter, which is what matters to him.

Chuck Nice then suggests a third option: rather than forcing oneself to look younger or simply accepting ageing, a person might accept that looking old can also be attractive.

Asked to explain in a few sentences why an audience should pay attention to him, Dr. Noc points out that in the discussion of creatine he did not recommend a specific product and gave no affiliate code. He says the same was true of the discussion of compounded peptides, with no affiliate link.

He says that is not the norm on social media, where people often tell viewers to take creatine using their code, and that affiliate payouts behind the scenes are often 30 to 50 percent.

He runs his Substack newsletter with no advertising, no partnership deals and no letter sponsors, and says it is funded only by readers. His stated reason is that his motivation is to give readers the best possible information so they keep funding the newsletter, and that the only way to be believed when recommending a certain action is not to be selling it.