[Category] Supplements — A Complete List of Supplements Verified by Scientific Research
About this category
Supplements are not meant to replace meals; rather, they are intended to be used as a supplement to address specific nutritional deficiencies or achieve specific goals.
Many over-the-counter supplements have limited evidence supporting their effectiveness, or studies have shown that their risks outweigh their benefits. On the other hand, there are also supplements that have been clearly shown to be beneficial.
In this category, items are organized into four tiers, ranging from Tier A (Highly Recommended) to Tier D (Not Recommended/Should Be Avoided).
🢢 Tier A: Strongly recommended (well-established evidence + clear benefits)—4 items
1. Vitamin D3 — Level 1: Strongly recommended
One-line summary: More than 80% of Japanese people are deficient. It reduces the risk of all-cause mortality, fractures, and respiratory infections.
Effect size:
– 25(OH)D ≤20 ng/mL (deficiency) vs. ≥30 ng/mL: all-cause mortality HR 0.86 (Bjelakovic et al., Cochrane 2014)
– Respiratory infections: 12% reduction in the risk of acute respiratory infections (Martineau et al., BMJ 2017; meta-analysis of 25 RCTs)
– Fractures in older adults: 15–20% reduction
– Depression symptoms: Symptoms improved in individuals with a deficiency
Recommended dosage:
– Adults: 1,000–2,000 IU per day
– Target serum 25(OH)D level: 30–50 ng/mL
– Adjustments will be made on an individual basis following confirmation via blood tests
Points to note:
– High doses (10,000 IU or more per day) carry a risk of hypercalcemia
– Potential for preventing arterial calcification with concomitant use of K2 (moderate evidence)
Supporting papers:
– Martineau AR, et al. (2017). Vitamin D supplementation to prevent acute respiratory tract infections. BMJ, 356:i6583.
– Bjelakovic G, et al. (2014). Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev.
👉 （Individual article coming soon）
2. Omega-3 fatty acids (EPA/DHA) — Level 1: Strongly recommended
One-line summary: Beneficial for cardiovascular health, inflammation, and cognitive function across the board. A must for anyone who doesn’t eat fish twice a week.
Effect size:
– Cardiovascular mortality: 8% reduction (Hu et al., JAHA 2019; meta-analysis of 13 RCTs, 125,000 participants)
– Myocardial infarction: less than 10%
– Deaths from coronary artery disease: 13% decrease
– Dementia: Benefits for mild to moderate cases
– Triglycerides: 20–30% reduction (at high doses)
Recommended dosage:
EPA+DHA 1,000–2,000 mg/day
– Patients with a history of cardiovascular disease: 2,000–4,000 mg/day
– Choose high quality (IFOS certification and purity)
– Store in the refrigerator, as it oxidizes easily
Fish Oil vs. Flaxseed Oil (ALA): The conversion rate of ALA to EPA is 5% or less. Fish oil is overwhelmingly more efficient.
👉 （Individual article coming soon）
3. Creatine — Level 1: Strongly Recommended
One-line summary: Boosts the effectiveness of strength training by 1.2 to 1.5 times. Evidence also supports muscle maintenance and cognitive function in older adults.
Effect size:
– Increased muscle strength: 8% additional effect (Kreider et al., J Int Soc Sports Nutr 2017)
– Increase in lean body mass: an additional 1.4 kg (combined with 10 weeks of strength training)
– Prevention of sarcopenia in older adults
– Cognitive function: Suggests improvements in memory and information processing speed (Avgerinos et al., 2018)
Recommended dosage:
– Creatine monohydrate: 3–5 g per day
– Do this every day, regardless of the time
– No loading required (gradually builds up in the muscles)
– Make sure to drink plenty of fluids
Safety:
– Proven safe for healthy adults through more than 30 years of research
– People with kidney dysfunction should consult a doctor
– "It's bad for your liver" is an urban legend
👉 （Individual article coming soon）
4. Magnesium — Level 2: Strongly Recommended
One-line summary: 70% of Japanese people are deficient. It plays a role in blood pressure, sleep, bowel movements, and muscle spasms.
Effect size:
– Risk of developing type 2 diabetes: 22% reduction (highest vs. lowest magnesium intake, Dong et al., 2011)
– Systolic blood pressure: decreased by 3–4 mmHg (at high doses)
– Improving sleep quality (in elderly people with insomnia)
– Reduced frequency of migraines
Recommended dosage:
– Men: 320–420 mg/day
– Women: 270–320 mg/day
– If you cannot get enough from your diet: 100–300 mg/day in supplement form
Selecting a format:
– Magnesium glycinate: Ideal for sleep, with few gastrointestinal side effects
– Magnesium citrate: Recommended for relieving constipation
– Magnesium oxide: May cause diarrhea; avoid
👉 （Individual article coming soon）
🟡 Tier B: Conditional Recommendation (Lack of data; beneficial for specific groups) — 3 items
5. Vitamin B12 (especially for people aged 50 and older and vegetarians) — Level 1: Conditional recommendation
Effect size:
– 10–30% of people aged 50 and older have reduced vitamin B12 absorption
– Deficiency: Pernicious anemia, peripheral neuropathy, cognitive decline
– Lowering homocysteine levels may reduce cardiovascular risk
Recommended:
– Ages 50 and older: 250–1,000 μg/day
– Vegetarians: 1,000–2,000 μg/day (methylcobalamin)
– If serum B12 is <300 pg/mL, supplementation is necessary
– Choose methylcobalamin over holpicinamide
👉 （Individual article coming soon）
6. Folic acid (essential for women planning to become pregnant) — Level 1: Conditional recommendation
Effect size:
– Taking folic acid before pregnancy reduces the risk of neural tube defects by 70%
– Potential for lowering homocysteine levels and cardiovascular protection in older adults
Recommended:
– Women trying to conceive or who are pregnant: 400–600 μg/day (from diet and supplements)
– Older adults: Aim for at least 400 μg from your diet
– People with the MTHFR gene polymorphism (10% of the Japanese population) require the methylfolate form
Note: There have been reports of concerns regarding high-dose folic acid in cases of undiagnosed colorectal polyps and certain types of cancer.
👉 （Individual article coming soon）
7. Probiotics — Level 2: Conditional recommendation
Effect size:
– Antibiotic-associated diarrhea: 52% reduction (Hempel et al., JAMA 2012)
– Irritable Bowel Syndrome (IBS): Symptom improvement
– Prevention of atopic dermatitis: Approximately 20% reduction during pregnancy and the neonatal period
– The systemic anti-aging effects in healthy individuals are limited
Recommended:
– Use only when the purpose is clear
– The specificity of the bacterial strain is important
– Lactobacillus rhamnosus GG, Bifidobacterium lactis BB-12, etc.
– Use in combination with prebiotics (dietary fiber)
👉 （Individual article coming soon）
🟠 Tier C: Potential but limited (research in progress) — 5 items
8. NMN/NR (NAD+ precursors) — Level 3: Experimental, Optional
Effect size:
– An increase in serum NAD+ levels has been confirmed (Yoshino et al., Nat Med 2021)
– The extension of human lifespan and healthy life expectancy remains unproven
– There are small-scale RCTs suggesting partial improvements in insulin sensitivity and muscle function
– Several reports have indicated mild benefits in patients with chronic conditions
Current Assessment:
– Shows promise in animal studies
– In humans, it’s still considered “interesting but lacks sufficient evidence”
– As of 2026, the cost will be high, ranging from several thousand to several ten thousand yen per month
– Long-term safety data is currently being collected
Recommendation: Worth trying if you have the budget, but prioritize the basic Tier A option
👉 （Individual article coming soon）
9. Resveratrol — Level 4: Not recommended
Current situation:
– Making headlines for its role in sirtuin activation
– Showed little to no effect in human clinical trials
– Bioavailability: 1% or less
– An unrealistic amount to consume from red wine
Recommendation: This supplement is a low priority. It would be wiser to invest in Tier A.
👉 （Individual article coming soon）
10. Taurine — Level 3: Experimental
Effect size:
– Inhibition of telomere shortening in animals (Singh et al., Science 2023)
– In humans, at the observational study level
– Has a supportive effect in patients with heart failure
Recommended:
– Healthy individuals: Currently insufficient evidence to make a recommendation
– It is possible that consuming seafood is sufficient
👉 （Individual article coming soon）
11. Metformin (prescription medication) — Level 2: Under a doctor’s supervision
Effect size:
– People with diabetes: All-cause mortality HR 0.77 (compared with the non-diabetic control group; Bannister et al., 2014)
– Suggestions of a reduced risk of colorectal and pancreatic cancer
– The TAME trial (currently underway) is investigating the effects of delaying aging in healthy individuals
Current situation:
– Recommended for diabetes and prediabetes
– Prescriptions for "anti-aging" treatments for healthy individuals are not covered by health insurance in Japan
– Not yet approved by the FDA
– Prescribed at some anti-aging clinics
Side effects: Gastrointestinal symptoms, impaired vitamin B12 absorption
👉 （Individual article coming soon）
12. Rapamycin/Rapalog — Level 4: Investigational
Current situation:
– The most reproducible effect on extending lifespan in animals
– Delaying human aging is not approved
– Clinical trials such as the TRIIM-X trial are currently underway
– Risk of side effects (immunosuppression)
Recommendation: It is still too early to make a general recommendation
👉 （Individual article coming soon）
🔴 Tier D: Not recommended / Should be avoided — 3 items
13. High-dose beta-carotene supplements — Level 1: Strongly avoid
Evidence:
– Increased risk of lung cancer (among smokers in the CARET and ATBC trials)
– 7% increase in all-cause mortality (Bjelakovic et al., JAMA 2007)
Recommendation: Avoid taking it as a supplement. Get it from vegetables and fruits.
👉 （Individual article coming soon）
14. High-dose vitamin E supplements — Level 1: Strongly avoid
Evidence:
– 400 IU/day or more: Increased risk of all-cause mortality (Miller et al., Ann Intern Med 2005)
– Prostate cancer: 17% increased risk in the SELECT trial
Recommendation: Avoid. Get your intake from nuts and olive oil.
👉 （Individual article coming soon）
15. High-dose calcium supplements (men and older adults) — Level 2: Avoid under certain conditions
Evidence:
– Calcium supplements exceeding 1,000 mg/day: Reported 27% increase in risk of myocardial infarction (Bolland et al., BMJ 2010)
– Conditional recommendation for postmenopausal osteoporosis in women
Recommended:
– Prioritize calcium intake from food
– Consult your doctor before taking supplements, and limit your intake to about 500 mg per day.
– Be sure to take it together with vitamin D, magnesium, and K2
👉 （Individual article coming soon）
📊 Guidelines for Prioritizing Supplements
The top priority (the cream of the crop)
- Vitamin D3 (beneficial for almost everyone)
- Omega-3 (people who eat fish less than twice a week)
- Magnesium (for people who tend to get insufficient amounts from their diet)
- Creatine (for people who do strength training and older adults)
These four items cost about 200 to 500 yen a day. They offer the best value for money.
We will consider it if the conditions are right
Depending on personal preference
8–12. NMN, metformin, etc.: Depends on financial means and interest in longevity
Avoid at all costs
13–15. Beta-carotene, high-dose vitamin E, and high-dose calcium for men
🎯 5 Principles for Choosing Supplements
Rule 1: Meals Come First
Supplements are not a "magic bullet." If you can manage to eat 350 grams of vegetables, fish twice a week, and 30 grams of nuts a day, you won’t need most supplements.
Principle 2: Define Your Objectives Clearly
Instead of just saying “for general health,” be specific—such as “vitamin D to prevent osteoporosis” or “creatine to build muscle.”
Rule 3: Confirm via blood test
Start taking supplements only after a blood test confirms deficiencies in vitamins D, B12, folic acid, iron, etc.
Principle 4: Choose a quality certification
- GMP Certification (Japan Health and Nutrition Food Association)
- IFOS Certification (Omega-3)
- USP Verified (U.S.)
- Products made by pharmaceutical manufacturers are generally of high quality
Rule 5: Check with your doctor for drug interactions
Particular caution is required when taking these medications in combination with warfarin, antidepressants, or antihypertensive drugs.
⚠️ Be careful of "ads" on sales sites
Many supplement ads exaggerate the evidence:
- "Rejuvenation to the age of ◯◯": According to the original research papers, the studies involved only animals or used surrogate markers
- "Recommended by a doctor": The doctor may have received compensation.
- "Patent Granted": A patent is not proof of effectiveness
- "Personal Accounts": Individual Differences, the Placebo Effect, and the Possibility of Coincidence
If you're unsure, check the original research paper on PubMed. This site always provides links to the papers.
🔗 Related Pages
- Home Page: Top 10
- Detailed Guide to Supplements
- Meal Category (Prioritizing Nutrition from Food)
- XPRIZE Healthspan Features
⚠️ Disclaimer
The information in this category is intended as a general guide to maintaining good health and is not intended to treat any medical conditions. Be sure to consult your doctor or pharmacist regarding interactions with prescription medications, as well as if you are pregnant, breastfeeding, or undergoing treatment for a medical condition.
evidage Editorial Department / Hydro Wing Lab Co., Ltd. / April 23, 2026
