The New Science of Supplements
Siim Land — Author of Metabolic Autophagy & Longevity Leap & Stronger by Stress, Slowest Aging Person on the Planet
Siim Land unveils the new science of supplements, navigating the booming $2
"Supplements like creatine, omega-3s, taurine, and others have solid evidence showing they support muscle, brain, metabolic, and cardiovascular health, helping your body recover, reduce inflammation, and extend health span when chosen and dosed properly."
Summary
- Popular evidence-based supplements include creatine, omega-3s, taurine, ashwagandha, vitamin D3, melatonin, NAC, astaxanthin, lutein, protein powders, caffeine, turmeric, berberine, and glycine. - Creatine aids muscle energy and brain function, especially helping cognitive recovery from sleep deprivation, with doses based on body weight. - Omega-3 fatty acids reduce cardiovascular risk and inflammation; supplementation depends on omega-3 blood status and typical diet. - Melatonin improves sleep and has anti-inflammatory effects; dose varies by individual and can enhance growth hormone during workouts. - Supplement industry lacks regulation; verify supplement quality through third-party testing and certificates of analysis to ensure ingredient accuracy.
Article
The supplement industry's dirty secret: what science really says about pills for longevity
Quality control crisis undermines health claims as expert reveals evidence-based approach to supplementation
The supplement industry may be worth over $200 billion in the United States alone, but the shocking reality is that 80% of products tested don't contain what their labels claim. This revelation, shared by health researcher Siim Land at the Hololife Summit 2025 Tokyo in October, underscores a fundamental crisis in an industry that millions trust with their health.
Speaking to an audience in Japan for the first time, Land presented a comprehensive overview of supplement science, cutting through marketing hype to reveal which products actually have robust clinical evidence behind them. His message was clear: while certain supplements show genuine promise, the lack of regulation means consumers must be extremely vigilant about product quality.
The verification problem
"The problem with supplements is the lack of regulation," Land explained to attendees at the Tokyo summit. "Eighty percent of investigated supplements didn't contain the ingredients listed on the label, so always look for third-party testing and certificates of analysis."
This sobering statistic from a 2024 analysis highlights why even evidence-based supplementation can fail. Without pharmaceutical-grade regulation, supplement manufacturers operate in a grey zone where label claims may bear little resemblance to actual contents.
Land's solution is straightforward: demand transparency. "Check for these certificates on the brand's website, or even email them to ask for proof," he advised. "If they do not provide these, be wary of their quality."
What the science actually supports
Despite quality concerns, Land's research identified several supplements with substantial clinical evidence from human trials. These include creatine, omega-3 fatty acids, taurine, vitamin D3, melatonin, and combinations like glycine with N-acetylcysteine.
The list contradicts much of the supplement industry's marketing, notably excluding many fashionable compounds with limited human evidence. "Most supplements don't have extensive evidence," Land noted, citing examples like urolithin A, various senolytics, and even NMN and NR, which despite raising NAD levels show "no conclusive outcomes for metabolic disease prevention as yet."
Beyond muscle: creatine's cognitive effects
Creatine, long established as the most researched sports supplement, has recently gained attention for brain health. Land described it as particularly effective for cognitive recovery rather than enhancement.
"Creatine helps your brain recover from cognitive deficits caused by sleep deprivation, jet lag, or trauma, supporting memory and cognition without giving cognitive superpowers," he explained.
Clinical trials in elderly people show memory and cognition support, with a pilot study in Alzheimer's patients revealing improvements. Land noted that his personal experience confirms creatine works best as "a sleep recovery supplement" following sleep deprivation or jet lag.
Interestingly, higher doses appear necessary for brain benefits than for muscle performance. A study using 350 mg per kilogram of body weight daily—approximately 28 grams for Land—showed improved cognition after sleep deprivation. For general use, he recommended around 100 milligrams per kilogram daily, adjusted for body weight.
The omega-3 advantage
Perhaps no supplement has more robust evidence than omega-3 fatty acids. "Hundreds of clinical trials show that omega-3 supplementation improves various health outcomes, specifically reducing the risk of cardiovascular events and mortality," Land said.
What makes omega-3s particularly interesting is their measurability in blood tests. Higher omega-3 index scores correlate with reduced mortality, heart disease, and Alzheimer's risk. Land pointed to Japanese dietary patterns as illustrative: "Japanese people, due to their high seafood consumption, have higher omega-3 index scores, which could partially explain their longer lifespans and lower incidence of heart disease and Alzheimer's."
The anti-inflammatory properties of omega-3s extend beyond cardiovascular protection to improving endothelial function, blood sugar, insulin sensitivity, and even promoting muscle growth and lean mass.
Dosing, however, requires individualisation. "If your omega-3 status is low (optimally 8% or higher), supplementation up to 3 grams per day may be needed," Land advised. "If your status is already high, supplementation may not be necessary."
Melatonin: more than sleep
While widely known as a sleep aid, melatonin's benefits extend far beyond its role as the "hormone of darkness." Land advocates for its use primarily as an anti-inflammatory agent.
"Melatonin is not only the hormone of darkness that improves sleep quality but also a powerful antioxidant that lowers inflammation, cholesterol, and blood sugar," he told the audience.
Higher doses, up to 10 milligrams daily, provide anti-inflammatory effects, whilst dosing for sleep remains highly individual. Land debunked a persistent myth: "Even high doses (up to 50 mg) do not suppress your own production, since it's regulated by circadian rhythm."
An intriguing finding suggests 5 milligrams of melatonin before workouts increases growth hormone, potentially aiding recovery and fat loss.
The glutathione connection
One of Land's favoured supplement combinations pairs glycine with N-acetylcysteine (NAC). Both serve as precursors to glutathione, a powerful antioxidant.
"Glycine and NAC are precursors to glutathione, a powerful antioxidant, reducing inflammation, improving physical function, cognition, and insulin resistance, especially effective in the elderly," he explained.
Animal studies show lifespan extension, whilst human trials reveal improvements across multiple aging markers. The combination reduces inflammation, enhances physical and cognitive function, decreases fat mass, and improves insulin resistance and blood pressure, particularly in older adults with lower glutathione status.
Effective doses reach 100 milligrams per kilogram daily, which Land acknowledged is "quite high but effective." Glycine remains well-tolerated even at 10 to 20 grams, though NAC proves harder to take in large doses.
Skin from within
Astaxanthin, a carotenoid found in colourful seafood and algae, has gained attention for skin anti-aging effects. Acting as an "internal sunscreen," it protects skin from UV damage whilst reducing photo-aging, wrinkle depth, and pigmentation.
Beyond cosmetic benefits, astaxanthin improves lipid profiles, lowers inflammation, blood pressure, and triglycerides at doses between 6 and 12 milligrams daily.
Similarly, lutein and zeaxanthin support eye health and vision whilst reducing inflammation, oxidised LDL, blood sugar, and skin aging. Effective doses range from 10 to 20 milligrams for lutein and 2 to 10 milligrams for zeaxanthin.
The berberine phenomenon
Social media's "nature's metformin" or "nature's ozempic"—berberine—does lower blood sugar and promote weight loss, though Land tempered expectations. "It is not as effective as metformin but still notable for blood sugar control," he noted.
Where berberine excels is cholesterol reduction, outperforming metformin in this regard, and targeting visceral fat around organs. Effective doses range from 500 to 1500 milligrams daily.
Vitamin D: essential but nuanced
The sunshine vitamin occupies a complex position in supplementation. Low blood levels associate with increased mortality and disease risk, making normalisation important. However, Land cautioned against excess: "Very high vitamin D can cause excess calcium and increase risk of osteoporosis or arterial calcification."
Benefits include potentially increased testosterone, lower cholesterol and triglycerides, and slower telomere shortening. Deficient individuals may need up to 10,000 IU daily, whilst 2,000 IU serves as maintenance. Land recommended combining vitamin D with K2, magnesium, and boron to aid absorption and prevent calcification.
Targeted stacks for specific goals
Land outlined several supplement combinations for different health objectives. His starter stack includes omega-3s, astaxanthin, glycine, vitamin K2, vitamin D3, magnesium, and niacinamide, covering "many aspects of health and anti-aging."
For longevity specifically, he adds trimethylglycine (supporting methylation and sports performance) and higher doses of vitamin K2 (up to 720 micrograms) for arterial plaque reduction.
Metabolic health benefits from taurine, omega-3s, glycine, NAC, berberine, aged garlic extract, curcumin, ginger, chromium, and benfotiamine (vitamin B1, essential for insulin sensitivity).
What doesn't make the cut
Notably absent from Land's evidence-based recommendations are many fashionable supplements. Multivitamins, whilst potentially supporting cognition in elderly people with nutritional gaps, "do not reduce mortality or chronic disease risk" and serve mainly as "nutritional insurance."
Urolithin A shows "some evidence for improving lower body strength, but that's about it." Senolytics like fisetin, quercetin, and apigenin have animal studies but "no human trials yet." Spermidine offers "some cognitive benefits in the elderly, but limited evidence."
The path forward
Land's presentation at the Hololife Summit offered a roadmap through supplement confusion: start with compounds showing robust clinical evidence, verify product quality rigorously, and adjust doses to individual circumstances including body weight and existing nutrient status.
"Use supplements as part of a lifestyle approach that includes diverse diet and regular exercise," he advised, emphasising that supplements "supplement but do not replace healthy habits."
As the supplement market marches towards $400 billion within the next decade, Land's evidence-based approach and emphasis on quality verification provide essential guidance for consumers navigating an under-regulated industry where label claims often prove worthless.
The message from Tokyo was clear: some supplements genuinely work, but only if they actually contain what they claim to contain.
Part of Hololife Summit 2025 Tokyo