Wondering if scientific research supports what’s listed in Project Blueprint? I spent days sifting through the evidence on PubMed and Google Scholar and compiled summaries of my findings for each supplement below.
Bryan Johnson’s protocol for “anti-aging” known as Project Blueprint has been attracting attention as the longevity field gains momentum. Indeed, even Netflix took heed of the increasing popularity and sponsored a 2025 documentary “Don’t Die: The Man Who Wants to Live Forever” that explores Bryan Johnson’s drive for immortality. But how do his supplement and pharmaceutical interventions hold up in the face of rigorously fact-checking published scientific literature?
Project Blueprint Issues
Unfortunately, his major contribution to the field of longevity is only the widespread interest he attracts through his marketing campaigns. As scientists well know, not many conclusions can be made based on n=1 (single person) experiments. In addition, he has far too many variables or strategies that may be affecting his aging to be able to interpret what’s causing what. Which supplements and drugs out of over the 100 that he takes on a daily basis are actually doing anything for him? Personally, I suspect most of the longevity benefits would come from his extreme lifestyle habits such as his optimized sleep, diet, and exercise routines than anything else he’s doing. But then again, since this isn’t science we’ll never know.
Project Blueprint Supplements and Drugs
I took the time to delve into the scientific literature regarding each supplement and pharmaceutical drug that is in Bryan Johnson’s Project Blueprint. 95% of what I found was terribly unexciting. The 5% of interventions he has employed that may be pushing the longevity needle further are already well-known in the geroscience community and are actively being studied for their gerotherapeutic potential. Here is what I found:
- Collagen peptides
- Description: Collagen is an important structural protein in tendons, joints, and ligaments.
- Evidence: Some trials found improved skin hydration, elasticity, and wrinkles. However, in these trials the experimental group also received a concoction of vitamins, minerals, and other ingredients in addition to collagen making it impossible to attribute the benefits to collagen supplementation alone.
- GOS
- Description: Galacto-oligosaccharides are prebiotics which act as food for good bacteria in the gut.
- Evidence: Human research with GOS is severely sparse. The few human studies available are in those with preexisting gastrointestinal disorders, making it difficult to extrapolate conclusions to a healthy population.
- Inulin
- Description: Inulin is a fiber found in plants that also acts as a prebiotic, feeding healthy gut bacteria.
- Evidence: Human research with inulin is severely sparse. Like GOS, the few studies available are in humans with gastrointestinal disorders.
- Acarbose
- Description: Acarbose is a drug used to treat diabetes. It works by preventing carbohydrates from being absorbed in the gut.
- Evidence: Acarbose is one of the few drugs that has been successful in the premier mouse lifespan research program known as the ITP. It was found to increase mouse lifespan by 16% in males and 5% in females. Measures of healthspan such as strength, coordination, and tissue specific markers also improved. In humans, it is proven to help in glycemic control in diabetics. However, research of its use in healthy individuals is lacking.
- NAC
- Definition: N-acetyl cystine is a precursor to the amino acid cysteine which goes on to form protein. It is known to have anti-oxidant properties.
- Evidence: In circumstances of high inflammation with increased reactive oxygen species (ROS), NAC has been shown to play a beneficial role in mitigating damage from ROS. However, its effect on individuals without systemic inflammation is unknown and may even be detrimental. Indeed, mild bursts of ROS from exercise or fasting has been shown to be pro-longevity. One study even found that supplementation with the anti-oxidants Vitamin C and D significantly shortened lifespan.
- Ginger
- Definition: Ginger contains hundreds of natural compounds being studied for possible longevity benefits.
- Evidence: Some human trials report improvement in metabolic parameters, lipid profiles, and a reduced risk of colorectal cancer. Mouse studies have found positive effects on dysbiosis, chronic inflammation, mitochondrial dysfunction, deregulated nutrient sensing, loss of proteostasis, and genomic instability. However, in these mouse studies they were using single compounds found in ginger but at massive doses that would be unreasonable for a human to consume.
- Curcumin
- Definition: Curcumin is the primary molecule found in turmeric.
- Evidence: Animal studies have found that curcumin can ameliorate the inflammation associated with certain diseases as well as limit the proliferation of cancer cells. Whether these benefits extend to humans is unknown. In humans, curcumin appears to improve metabolic function in diabetics but not in non-diabetics. It has had no effect on preventing or treating cancer in human trials.
- Red yeast rice
- Definition: Red yeast rice is the product of yeast grown on white rice giving the rice a reddish color. It has been used in traditional Chinese medicine for centuries.
- Evidence: It’s bioactive molecule, monacolin K, is known to lower cholesterol. In studies comparing it to the “weaker” statins, it has been shown to have equal efficacy in cholesterol lowering ability. It has not yet been compared to more potent statins.
- EPA/DHA
- Definition: EPA and DHA are both omega-3 fatty acids found in fish. They are essential fats, meaning that our bodies need them but cannot produce them so we are forced to get them through diet.
- Evidence: The REDUCE-IT trial showed that in people with elevated fasting triglyceride levels EPA decreases the risk of having a cardiovascular event by 25% over 5 years. In patients with hypertriglyceridemia, excessive consumption of DHA (over 3g daily) has been reported to increase LDL levels. Studies of EPA and DHA on human cognition have been inconclusive due to mixed results.
- Garlic
- Evidence: Garlic has failed to significantly improv lipid panels or blood pressure. Human trials have demonstrated decreased level of inflammatory biomarkers with garlic. Some trials report garlic supplementation to decrease the number, duration, and severity of the common cold.
- Metformin
- Definition: A prescription drug used to improve glycemic control in diabetics.
- Evidence:
- Arguments for: Metformin has been shown to positively modulate the biological hallmarks of aging. Meta analyses have found metformin to reduce cardiovascular mortality and all-cause mortality in patient with coronary disease. Preliminary results from the metformin aging study MILES indicate that metformin may induce pro-longevity epigenetic modifications.
- Arguments against: Failed to extend mouse lifespan in the ITP. Research has found that when combined with exercise, metformin actually blunted the positive effects of exercise such as muscle growth, aerobic capacity, and VO2 max. Meta analyses have not found metformin to reduce cancer or dementia incidence.
- NR/NMN
- Definition: NR is a precursor of NMN which is a precursor of NAD. NAD is an important molecule that carries out a number of crucial cellular functions. It is involved in energy metabolism, epigenetic integrity, and cell signaling. As we age, NAD levels decrease. This observation gave rise to the idea that supplementing with NAD may promote longevity. However, NAD does not get absorbed in the gut and intravenous NAD does not seem to be taken up into cells. Instead, scientists have turned to investigating precursors of NAD (NR and NMN) that do.
- Evidence: Despite the popularity of NR and NMN, there is little evidence to support their use as pro-longevity agents. NR failed to increase mouse lifespan in the ITP. The little human research that is available is often funded by the same companies that are selling the NR/NMN product. Their labeling as supplements has allowed companies to sell them “over the counter” without needed evidence to support their use. Based on these studies, there does not yet seem to be significant side effects, at least in the short term. On a more optimistic note, several promising studies have found that NR/NMN decreased the risk of developing non-melanoma skin cancers. Much more research investigating effects on human healthspan versus long-term side effects are needed.
- Probutyrate
- Definition: Probutyrate is a brand name of the supplement butyric acid. Butyric acid is a fatty acid that is made by bacteria in the colon and used by cells in the colon as energy.
- Evidence: Human studies report clinical efficacy in patients with inflammatory bowel disease, specifically, Crohn’s disease. Other studies suggest positive effects on gut health in alcoholics and smokers who are known to have inflamed GI tracts. There is a lack of studies investigating butyric acid in healthy individuals.
- Proferrin
- Definition: Proferrin is the brand name of an iron supplement. Iron is used to supplement those who are iron deficient, usually manifesting as anemia.
- Evidence: Iron should only be supplemented in patients with known deficiencies. Iron overload is a well known issue that consuming too much iron has on individuals. It causes iron to deposit in bodily organs, eventually leading to organ damage.
- Melatonin
- Definition: Melatonin is a hormone produced by the pineal gland in the brain. It regulates our circadian rhythm and tells the body when it’s time for bed.
- Evidence: Meta analyses of human trials conclude that melatonin supplementation significantly improves sleep quality. It appears that Bryan Johnson may be using melatonin because his caloric restriction makes it difficult to fall asleep due to increased release of catecholamines.
- Extra virgin olive oil
- Definition: Extra virgin means the olive oil has not been refined or modified with heat or chemicals. This preserves the antioxidants and polyphenols in the oil. It’s rich in monounsaturated fats which experts agree are considered healthy fats.
- Evidence: A reasonable amount of evidence supports the claims that extra virgin olive oil has health benefits. Preclinical studies have found supplementation to decrease inflammatory markers, improve circulation, decrease atherogenesis, control proliferation in some cancer cells, and improve bone homeostasis. Human studies have reported improved cardiovascular outcomes and mortality, improved lipid and cholesterol profiles, increased weight loss, decreased incidence of developing certain types of cancers, and an improved gut microbiota. However, excess amounts of extra virgin olive oil over the recommended 4-5 tablespoons daily can increase weight due to its high caloric content.
- High polyphenol cocoa
- Definition: Polyphenols are organic molecules commonly found in plants.
- Evidence: Human and animal research have found that some polyphenols have anti-oxidant and anti-inflammatory properties. One randomized clinical trial found that coca extract supplementation reduced cardiovascular death in older adults by 27% but did not reduce the number of total cardiovascular events. Other trials found no effect of cocoa supplementation on cognition or diabetes incidence.
- Pea/hemp protein
- Definition: Hemp is a type of cannabis plant that is not psychoactive (low in THC) but high in CBD. Both pea and hemp protein can be used to supplement daily protein intake to support muscle maintenance and growth.
- Evidence: It is controversial whether plant proteins such as pea and hemp are better or worse than traditional milk protein supplements such as whey and casein. From a longevity perspective, the arguments for plant protein are that they contain less branched chain amino acids which activate mTOR. The arguments for animal-based protein are that they are higher quality protein allowing for easier muscle growth and maintenance.
- Fermented foods
- Examples: kombucha, yogurt, kimchi, miso, sauerkraut, etc. It is believed that fermented foods favorably interact with the gut microbiome.
- Evidence: Few studies have actually investigated whether fermented foods modulate gut bacteria. Although there is a lack of clinical trials, some epidemiological studies suggest that consuming fermented foods boosts cardiovascular and metabolic health.
- Rapamycin
- Definition: Rapamycin is a drug that is currently used in medical practice as a means of suppressing the immune system at high doses. However, much lower doses are currently being investigated for longevity-enhancing effects. Rapamycin inhibits mTOR, which is generally known to enhance longevity by mimicking calorie restriction.
- Evidence: Rapamycin is the only drug that has been proven to extend lifespan in different species across the evolutionary tree including yeast, C. Elegans, flies, and mice (including the ITP). In addition to extending lifespan, it has increased components of animal healthspan such as better memory and less frailty. Despite the excitement in the geroscience community over rapamycin, human clinical trials investigating the effectiveness, side effects, and optimal dosing regimens are lacking. However, there are a number of early phase human clinical trials currently underway.
- 17a-E2
- Definition: 17 “alpha” estradiol is a weak agonist of the estrogen receptor.
- Evidence: Male mice treated with 17a-E2 had improved metabolic parameters in addition to increased lifespan in the ITP, but not female mice. Unlike rapamycin, the mechanism by which it exerts pro-longevity effects is unknown. Recent studies in monkeys found improvements in metabolic function but with the side effect of increased feminization including testicular atrophy and suppressed androgens. There are a lack of human studies.
Key Takeaways
- In general, current research does not support Project Blueprint’s supplements from adding significant longevity benefits in healthy individuals.
- There is known/potential harm in over-supplementation with many of the supplements listed.
- Bryan Johnson’s supplement list is likely highly personalized to him and should not be generalized to a population.