100 Supplements Ranked Worst to Best (Ultimate Supplement Tier List 2025)

While melatonin is commonly taken as a sleep aid at 0.3-5 mg nightly, Land uses it as an intermittent hormetic antioxidant therapy. He believes the primary value of melatonin for longevity is not its acute sedative effects but its ability to directly scavenge free radicals and to regulate glutathione synthesis and autophagy—key cellular repair processes that are active during sleep. By spiking the system with a supraphysiologic dose a few times a month, he aims to stimulate these protective pathways without downregulating endogenous melatonin production. This approach is based on the concept that short bursts of oxidative or metabolic stress (in this case, a large antioxidant creating a redox signal) can trigger lasting repair mechanisms. He acknowledges that daily high doses would be counterproductive, but an infrequent pulse can be beneficial.

Land emphasizes that directly supplementing glutathione has poor bioavailability and may even be pro-oxidative if not properly regulated. Instead, he advocates for the glycine + NAC combo, which provides the two rate-limiting building blocks for glutathione synthesis. He references an older body of clinical trials (a few years ago) where glycine and NAC together improved gait speed, grip strength, metabolic health, inflammation, and body composition in older adults. This protocol builds on the concept that aging is associated with a decline in glutathione, and that precursor loading is a safer, more natural way to restore levels. He considers glycine a 'god tier' supplement on its own, and NAC a perfect partner, ranking both very highly.

Land is adamant that vitamin D supplementation without K2 and magnesium is a mistake. He explains that vitamin D increases intestinal calcium absorption and can raise serum calcium levels, which, if not regulated, might deposit in arteries instead of bones. Vitamin K2 (especially as MK-7) activates matrix Gla protein and osteocalcin, which pull calcium into bone and away from soft tissues. Magnesium is required for the enzymatic conversion of vitamin D into its active form and also plays a role in bone health. This trio is a foundational part of his recommendation, and he places both vitamin D3 and K2 in 'god tier' and magnesium glycinate/glycinate as top forms.

Land corrects the misconception that creatine acts as a general cognitive enhancer. He references a sleep deprivation study where creatine brought performance back to baseline and slightly above, but it does not elevate cognition in well-rested individuals. The mechanism is related to its role in ATP buffering—the brain consumes a lot of energy, and when energy systems are stressed (sleep loss, injury, neurodegeneration), creatine helps maintain function. He places creatine in 'god tier' for both physical and brain resilience, but is explicit: it's not a limitless pill. This messaging is important to prevent overhyped expectations from healthy users.

Land explains the paradox: carnosine is beneficial for skin (reduces glycation) and muscle (buffers acid), but as a direct supplement it's poorly bioavailable. Beta-alanine, an amino acid, is converted in the body to carnosine and effectively raises tissue levels. He notes some evidence for cholesterol lowering as well. The main downside is the characteristic flush/itch, which some find intolerable. He places beta-alanine in 'good' tier, acknowledging its utility but with the caveat that the itching can be annoying. He contrasts it with HMB, which he would only recommend for elderly people with sarcopenia, not younger athletes.

Land places ashwagandha, specifically the KSM-66 standardized extract, in 'god tier' due to a robust body of human evidence. He notes that it not only reduces stress and aids sleep but also shows positive effects on testosterone and even VO2 max. He addresses the anecdotal reports of anhedonia or reduced libido in some users, stating that he has taken it on and off without any adverse effects, suggesting individual variability. He emphasizes that if you are one of those who react poorly, it's not for you, but the data support its efficacy.

Land argues that the human clinical evidence strongly supports resveratrol's benefits only in metabolically compromised populations. In healthy individuals, it may do more harm than good—studies show it can lower exercise adaptations and testosterone. He places it in 'junk' tier for healthy users, a contrarian stance compared to its long-held reputation. This aligns with a broader pattern he observes: many supplements that work for the sick fail to benefit the already healthy. He warns that taking resveratrol without a metabolic need is not just ineffective but potentially counterproductive.

Land highlights that mouse studies on genetically diverse strains show no lifespan extension, and human data fail to show a longevity benefit in non-diabetics. He points to clinical evidence that even healthy individuals taking metformin experience declines in testosterone and VO2 max, which are undesirable. He acknowledges that the drug's severe blood sugar lowering might theoretically offer some longevity benefit, but the trade-offs appear significant. He ultimately ranks it 'bad', not 'junk', because it does have a role for those with metabolic disease—similar to resveratrol. This perspective directly refutes the widespread 'metformin for everyone' meme.

Land distinguishes between melatonin's acute soporific effect and its antioxidant properties. He explains that melatonin is a potent free radical scavenger that also upregulates endogenous glutathione and autophagy pathways during sleep. By pulsing a high dose a few times per month, he aims to boost these protective mechanisms without desensitizing circadian receptors or causing dependency. This protocol is based on the concept of hormetic stress—a temporary high dose triggers repair. He acknowledges that daily use might blunt natural production, so he opts for intermittent high-dose cycles.

Land dissects the biochemistry: leucine is the primary signal for mTOR, but actual muscle protein synthesis requires all nine essential amino acids. When only BCAAs are provided, the body attempts to balance the amino acid pool by breaking down muscle tissue to liberate the missing EAAs, resulting in net catabolism. He references studies showing that BCAA supplementation alone does not increase muscle protein synthesis and can actually elevate markers of muscle breakdown. The only arguable benefit is reduced soreness or increased energy during exercise due to BCAA oxidation, but for muscle growth or preservation, they are counterproductive. He ranks BCAAs 'junk tier' and urges people to use EAAs or whole protein instead.

Land highlights a recent study implicating lithium deficiency in neurodegeneration and Alzheimer's. He notes that low-dose lithium (1 mg) forms like lithium orotate are far below the doses used for bipolar disorder (often 900-1800 mg lithium carbonate) and pose minimal kidney risk. The evidence, while observational, points to a possible essential trace mineral role. He finds the data 'quite interesting' and places it in the 'good' tier for mental health and potential dementia prevention, while cautioning that it's still early to make definitive claims. This recommendation is cautious but forward-looking, recognizing the gap between epidemiological signals and interventional trials.