I Researched 100+ Supplements: Full Breakdown

Siim emphasizes that taking glycine is better than direct glutathione supplementation because the body can produce glutathione on demand from glycine, avoiding the risk of disrupting healthy redox balance. Human studies show glycine taken before bed shortens sleep onset and improves sleep quality, likely through its calming neurological effects. He also notes glycine’s broader roles in collagen synthesis, liver health, and reducing blood sugar and glycation.

Siim highlights that the most underappreciated benefit of creatine is its ability to normalize cognition after prolonged wakefulness – attention, memory, and focus drop after 20+ hours awake, and creatine brings them back to baseline. He also explains that creatine’s primary physical benefit is increasing power, speed, and explosiveness, not muscle mass, and it reduces muscle damage to speed recovery. The brain’s high creatine demand underpins the cognitive rescue effect.

Siim categorizes NAC as near-medical grade because its clinical applications go beyond typical supplements – it is used for acetaminophen overdose liver rescue and for mucolytic therapy in respiratory diseases. Human trials also show it improves insulin sensitivity in PCOS, reduces OCD symptoms, and supports fertility and liver function. For those with lung issues, NAC can be particularly effective at easing breathing and reducing exacerbations.

Siim explains that the best data on multivitamins comes from studies on older adults who tend to under-eat and consume processed foods, leading to deficiencies. In that group, multivitamins improve cognition and memory. He personally uses a multivitamin as a daily insurance policy. For someone with a balanced, whole-food diet, a multivitamin is probably unnecessary but harmless.

Siim notes that while typical sleep doses are 1–5 mg, clinical studies have used 10 mg to demonstrate reductions in inflammatory markers, lipids, and blood sugar. He also links high melatonin to glymphatic toxin clearance. He dispels the myth that melatonin lowers testosterone in adult men (it can delay puberty if given to children, but not in adults). The 10 mg protocol is evidence-backed but should be timed for nighttime.

Siim clarifies that theanine is not a true nootropic on its own – its benefits emerge only in combination with caffeine. It smooths out caffeine’s stimulatory jitters. He personalizes the advice: anxious types will benefit most, while calm individuals may find theanine superfluous. This stack is a simple way to improve the subjective experience of stimulants.

Siim acknowledges the controversy that collagen studies are often sponsored by supplement companies, yet he maintains that there is enough controlled evidence supporting skin elasticity and hydration. He stresses that only collagen peptides – not standard collagen powder – have the bioavailability to achieve these effects. Joint pain relief and glycine-mediated blood sugar lowering are additional benefits.

Siim points out that while resveratrol has human evidence for improving metabolic parameters in diabetic/overweight individuals, its strong antioxidant effect can interfere with exercise adaptations. He advises timing it away from workouts. This is a classic example of hormesis interference: the supplement that reduces oxidative stress can also reduce the beneficial stress of exercise.

Siim Land explains that creatine is one of the most researched supplements, and the hair-loss myth stems from a single study that only measured DHT levels, not hair counts. A recent controlled trial gave subjects creatine and found no effect on DHT or hair loss whatsoever, and he argues there is no biological pathway for creatine to trigger androgenic alopecia. While some individuals report hair loss anecdotally, the clinical data do not support it, and other factors are likely at play.

Siim counters the narrative that omega-3s cause inflammation by citing randomized controlled trials where subjects taking omega-3s had lower skin inflammation and greater UV protection after three months. He also dismisses a recent observational study linking omega-3s to cognitive decline, emphasizing that multiple higher-quality RCTs show cognitive and mental health benefits. The overall take is that omega-3s are anti-inflammatory and skin-supporting, not harmful.

He describes that the glymphatic system – the brain's waste clearance network active during sleep – is boosted by melatonin, potentially flushing out BPA and microplastics. Although the evidence is still preliminary, he finds it a promising area. He also debunks the myth that melatonin lowers testosterone in adult men (child studies suggest it may delay puberty, but no testosterone suppression in adults) and notes that mega-dose studies (100–1,000 mg) exist and merit further exploration.

Siim clarifies that berberine does lower blood sugar, but metformin is significantly better for that. However, berberine surpasses metformin in lowering total and LDL cholesterol, though it is not as potent as statins. It also reduces blood pressure, inflammation, and visceral fat. Because of its antibacterial properties, he cautions those with normal gut health about microbiome disruption. This insight helps target berberine to the right audience (those with high cholesterol and insulin resistance) rather than as a general glucose hack.

He concedes that some individuals report anhedonia, but the weight of randomized trials demonstrates significant cortisol lowering, stress reduction, and downstream benefits like higher testosterone and better sleep. He also points to a human study showing increased VO2max, an underappreciated athletic edge. He frames the anhedonia reaction as idiosyncratic, not a reliable outcome, and suggests that the overall risk-to-benefit ratio favors use for stress-related conditions.

Siim notes that the study started with 29 people receiving urolithin A, but only 6 showed increased mitophagy markers – a classic case of cherry-picking a small responder group. The endurance benefit was based on a six-minute walking test in elderly individuals, far from a rigorous VO2max assessment, and grip strength/upper body strength did not improve. He also argues that exercise already upregulates mitophagy, so supplementation likely adds nothing for physically active people. He calls for larger, better-designed studies before accepting any longevity claims.

He explains that boron can lower sex hormone binding globulin (SHBG), thereby raising free testosterone, but only if SHBG is elevated. In his own trial, his SHBG was already low due to sufficient calorie and carbohydrate intake, so boron did nothing. He advises that optimizing SHBG through diet may be more effective than supplementing, and that boron is not a general testosterone booster.