Lab Notes: GLP-1s, Peptides, and Heart Health

This phase 3 trial evaluated once-weekly semaglutide 2.4 mg in patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stage 2 or 3. Semaglutide, already approved for type 2 diabetes and obesity, is now being tested for liver health. The results could offer a much-needed treatment for this increasingly common condition, which often goes undiagnosed. While we don't have specific numbers here, the high study score suggests robust evidence. For those with fatty liver disease, this is a promising development, but more details are needed.

The SURMOUNT-4 trial investigated whether continued tirzepatide injections maintain weight loss over 88 weeks. Participants who continued saw sustained reduction, while those switched to placebo regained weight. This confirms that weight loss drugs often require ongoing use to maintain benefits. However, the study was funded by Eli Lilly, the maker of tirzepatide, which is a major conflict of interest. Always consider the source when evaluating such findings.

This randomized controlled trial assessed liraglutide 3.0 mg vs placebo in overweight or obese individuals with insulin-treated type 2 diabetes. Liraglutide led to significant weight loss and improved glycemic control. Given that people with diabetes often struggle with weight, this adds another tool. But again, the study was funded by Novo Nordisk, the manufacturer. Also, the cost and side effects should be considered.

A common claim is that liraglutide produces 8% body weight loss in non-diabetic patients. This claim likely originates from trials like the SCALE program. However, the actual percentage varies by dose and population. In the SCALE Obesity and Prediabetes trial, liraglutide 3.0 mg resulted in an average weight loss of about 8% at 56 weeks. So the claim is generally accurate, but it's an average—some lose more, some lose less.

A systematic review and meta-analysis of randomized controlled trials looked at oral and topical peptides for skin aging. The review assessed outcomes like hydration, elasticity, wrinkles, and brightness. Overall, there is some evidence that peptides can improve skin hydration and elasticity, and reduce wrinkle depth. However, the quality of studies varies, and effects are modest. It's also unclear which peptides are most effective. If you're considering peptide products, manage your expectations.

A 12-month program of combined endurance and resistance exercise in heart failure with preserved ejection fraction (HFpEF) failed to significantly improve a composite clinical outcome (modified Packer score) compared with usual care. The Kendall's tau-b was -0.073 (P=0.17), indicating no benefit on mortality, hospitalizations, exercise capacity, diastolic function, symptom class, and global self-assessment. This challenges the notion that exercise is a cure-all for HFpEF, but it doesn't mean exercise is useless—it's still beneficial for overall health.

While the primary composite outcome didn't improve, a secondary analysis found that exercise training improved New York Heart Association (NYHA) functional class. The odds of improvement were 7.77 times higher (95% CI 3.73–16.21) compared to usual care at 12 months. This suggests that patients felt better and had fewer symptoms, even if objective measures didn't change. However, as a secondary endpoint, it should be considered exploratory.

Another secondary analysis from the same trial evaluated the E/e' ratio, a measure of diastolic function. There was no significant difference between the exercise and usual care groups. This indicates that while exercise improves symptoms, it may not reverse the underlying diastolic dysfunction. This is important because it suggests that exercise's benefits are not due to changes in heart stiffness.

This study evaluated the effect of Eurycoma longifolia water extract (Physta®) on menopausal quality of life and mood in women aged 40–55. It found some improvements at 50mg and 100mg daily. However, the study was sponsored by Biotropics Malaysia Berhad, the manufacturer of Physta®, which is a major conflict. While results seem promising, independent studies are needed to confirm these findings. Always be wary of supplements backed by industry-funded research.

Some sources claim that tongkat ali supplementation improves overall mood and reduces tension and anger. This claim aligns with the study mentioned earlier, but the study's conflict of interest makes it less reliable. More independent research is needed to validate these mood benefits. While tongkat ali is popular for libido and stress, the scientific evidence is still thin.

In a 12-week trial, 100 mg/day of Eurycoma longifolia water extract showed no statistically significant benefit on mood disturbance in menopausal women. The decrease in mood disturbance scores was 38.6% with the extract vs 30.1% with placebo (p=0.235). So the difference could be due to chance. This contradicts claims that it improves mood. Perhaps the benefits are limited to certain symptoms or doses.

Despite not improving mood significantly, the same study found that a 100 mg daily dose of Eurycoma longifolia reduced overall menopausal symptom scores by about 34% from baseline, compared to 23% with placebo (p=0.049). It specifically improved physical and sexual symptoms. So while mood didn't improve, other symptoms did. This suggests that tongkat ali may be more helpful for physical and sexual aspects of menopause.

Another analysis from the same study found no significant sustained changes in reproductive hormones (progesterone, testosterone, estradiol, FSH, LH) with 50mg or 100mg daily, except for a transient progesterone increase at week 6 that resolved by week 12. This suggests that the extract doesn't have a major hormonal effect. This is reassuring for safety, but it also raises questions about how it works.

Supplementation with Eurycoma longifolia at up to 100 mg/day for 12 weeks did not significantly alter estradiol, FSH, LH, progesterone, or testosterone levels in menopausal women. This suggests hormonal neutrality within that timeframe. That's good news for those concerned about hormonal side effects, but it also means the benefits are likely through other pathways.

In the same trial, daily supplementation with 50mg or 100mg of Physta® was well-tolerated, with no serious adverse events and no clinically significant changes in vital signs, liver function, kidney function, or metabolic parameters compared with placebo. This supports its short-term safety as a dietary supplement. However, long-term safety data are still lacking.

This video claims that certain habits can keep you young past 30. The pro score is 51 to 17 against, suggesting moderate support. While we don't have specific details, common habits include sleep, exercise, diet, stress management, etc. Many are indeed backed by science. But be wary of oversimplification. Healthy lifestyle choices certainly contribute to longevity and healthier aging.

This video promotes a daily popcorn recipe as an unexpected health food. Popcorn is a whole grain, high in fiber, and relatively low in calories if air-popped. The pro score is 48 vs 4 against, indicating strong support. However, the health benefits depend on preparation: added butter, oil, and salt can sabotage its healthiness. So choose air-popped or lightly seasoned popcorn.

This video suggests that a vitamin prevents age spots. The claim likely refers to vitamin C or vitamin E, which are antioxidants. Age spots are caused by sun damage and oxidative stress. Some studies show that topical vitamin C can lighten age spots, but dietary intake? Oral vitamins have mixed evidence. The pro score is 41 to 0 against, so it's considered plausible. But we need more research.

This video claims scientists found the #1 exercise for metabolic health with 10x better results. The pro score is only 36 vs 31 against, meaning it's controversial. Likely it's about high-intensity interval training (HIIT) vs steady-state cardio. While HIIT can be efficient and effective, the claim of 10x better is likely exaggerated. Both forms of exercise have benefits. The verdict is not clear-cut.

This video questions the healthfulness of beans and fruit, referencing a new study. The pro score is 29 vs 8, so the video is mostly pro-beans/fruit but raises questions. Possibly about carb content or antinutrients? Beans and fruit are generally healthy, rich in fiber and nutrients. But some people may need to moderate due to digestive issues or carb sensitivity. The study might have found something specific, but without details, we can't judge.