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Dr. Grey AI

Condition

Frailty

Frailty is a state of reduced resilience in which a minor event, like an infection or a medication change, can trigger a big drop in everyday function. The evidence is rated strongest for protein and vitamin D, though whey protein trials in about 1,400 people found no clear difference in function. A small zinc study found function improved, but that evidence is limited.

Supplements studied
5
Graded outcomes
4
Trials
5
People studied
35,074

Evidence by supplement

  • Strong
  • Moderate
  • Limited
  • Very limited

5 supplements

Zinc

Zinc: outcomes studied for Frailty
GradeOutcomeEffectSizeStudiesPeopleStudies list
Functionality in Elderly or Injured

Small Improvement

Improves (the measure goes up)Small effect61 people
IGF-1Improves (the measure goes up)2 studies61 people

Studies that measured igf-1

Medium-chain Triglycerides

Medium-chain Triglycerides: outcomes studied for Frailty
GradeOutcomeEffectSizeStudiesPeopleStudies list
Body Fat

Small Decrease

Improves (the measure goes down)Small effect56 people
Muscle MassImproves (the measure goes up)1 study56 people

Studies that measured muscle mass

StrengthImproves (the measure goes up)1 study168 people

Studies that measured strength

Walking AbilityImproves (the measure goes up)1 study168 people

Studies that measured walking ability

Whey Protein

  • Functionality in Elderly or Injured
  • Muscle Mass: improves
  • Strength: improves
Whey Protein: outcomes studied for Frailty
GradeOutcomeEffectSizeStudiesPeopleStudies list
Functionality in Elderly or Injured

No effect

NoneNo effect1,398 people
Muscle MassImproves (the measure goes up)5 studies1,398 people

Studies that measured muscle mass

and 2 more on the Whey Protein page

StrengthImproves (the measure goes up)2 studies1,398 people

Studies that measured strength

DHEA

  • Body Fat
  • Estrogen: changes; see studies
  • Testosterone: improves
DHEA: outcomes studied for Frailty
GradeOutcomeEffectSizeStudiesPeopleStudies list
Body Fat

No effect

NoneNo effect83 people
EstrogenChanges; see studies8 studies182 people

Studies that measured estrogen

and 5 more on the DHEA page

TestosteroneImproves (the measure goes up)3 studies182 people

Studies that measured testosterone

Bone Mineral DensityImproves (the measure goes up)2 studies182 people

Studies that measured bone mineral density

Muscle MassImproves (the measure goes up)2 studies83 people

Studies that measured muscle mass

Serum DHEAImproves (the measure goes up)2 studies182 people
Cognitive DeclineImproves (the measure goes down)1 study83 people
IGF-1Improves (the measure goes up)1 study83 people
Functionality in Elderly or InjuredImproves (the measure goes up)182 people
IGF Binding ProteinImproves (the measure goes up)83 people
Sex Hormone Binding GlobulinImproves (the measure goes up)99 people

Vitamin D

  • Fracture Risk: changes; see studies
Vitamin D: outcomes studied for Frailty
GradeOutcomeEffectSizeStudiesPeopleStudies list
Fracture RiskChanges; see studies1 study42,279 people

Studies that measured fracture risk

Key findings

  • Functionality in Elderly or InjuredZincImproves (the measure goes up)
  • Body FatMedium-chain TriglyceridesImproves (the measure goes down)

The Frailty Prevention and Management protocol

2 primary supplements · 6 supporting supplements

  • Protein Supplements1.2–1.5 g protein/kg body weight daily (include leucine-rich sources)
  • Vitamin D1,000–4,000 IU daily (higher if deficient)

See the full protocol

Shop the evidence-backed picks

Fullscript collectionMuscle, performance and healthy ageing: evidence-graded picksOpen on Fullscript

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Studies cited

100 studies from PubMed

  1. Effect of vitamin D supplementation for major adverse cardiovascular events: a meta-analysis based on randomised controlled trials.Br J Nutr, 2025 · PMID 40685646
  2. Optimal Vitamin D Status: Evidence and GuidelinesEndocr Connect, 2019 · PMID 30697582
  3. Vitamin D and Cancer Prevention: A Comprehensive ReviewNat Rev Cancer, 2019 · PMID 30612257
  4. Effects of Vitamin D Supplementation on Musculoskeletal Health: A Systematic Review and Meta-AnalysisLancet Diabetes Endocrinol, 2018 · PMID 30445434
  5. Vitamin D and Prevention of Respiratory Tract Infections: A Systematic Review and Meta-AnalysisBMJ, 2018 · PMID 29878139
  6. Effects of Vitamin D Supplementation on Depression: A Systematic Review and Meta-AnalysisNutrients, 2018 · PMID 29481980
  7. Vitamin D and Immune Function: A ReviewJ Investig Med, 2018 · PMID 30125852
  8. Vitamin D Supplementation for Prevention of Mortality: A Meta-AnalysisCochrane Database Syst Rev, 2018 · PMID 29789217
  9. Vitamin D Supplementation During Pregnancy: Safety and Efficacy ReviewNutr Rev, 2018 · PMID 29459995
  10. Vitamin D Supplementation: A Comprehensive Review of Efficacy for Various Health OutcomesLancet Diabetes Endocrinol, 2017 · PMID 28768407
  11. Vitamin D Deficiency: Global Health PerspectiveMed Clin North Am, 2017 · PMID 27986512
  12. Vitamin D and Cardiovascular Disease: A Review of EvidenceAnn Intern Med, 2017 · PMID 28440249
  13. Vitamin D and Bone Health in Adults: A Systematic ReviewLancet, 2017 · PMID 28212022
  14. Vitamin D3 supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D statusEur J Nutr, 2015 · PMID 26621634
  15. Association of A1C levels with vitamin D status in U.S. adults: data from the National Health and Nutrition Examination SurveyDiabetes Care, 2010 · PMID 20215453
  16. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination SurveyAm J Hypertens, 2007 · PMID 17586404
  17. Effects of dehydroepiandrosterone and atamestane supplementation on frailty in elderly menJ Clin Endocrinol Metab · PMID 16804050
  18. Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older womenJ Am Geriatr Soc · PMID 20863330
  19. Effect of 1-year oral administration of dehydroepiandrosterone to 60- to 80-year-old individuals on muscle function and cross-sectional area: a double-blind placebo-controlled trialArch Intern Med · PMID 12639206
  20. Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolismAging Male · PMID 14628495
  21. Effects of dehydroepiandrosterone vs androstenedione supplementation in menMed Sci Sports Exerc · PMID 10613429
  22. Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipidsClin Endocrinol · PMID 21521341
  23. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trialOsteoporos Int · PMID 18084691
  24. Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjectsClin Endocrinol · PMID 16487434
  25. Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in menJ Clin Endocrinol Metab · PMID 12843164
  26. Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipidsJ Womens Health · PMID 15989411
  27. Lack of dehydroepiandrosterone effect on a combined endurance and resistance exercise program in postmenopausal womenJ Clin Endocrinol Metab · PMID 18029465
  28. Impact of DHEA supplementation on testosterone and estradiol levels in postmenopausal women: a meta-analysis of randomized controlled trials assessing dose and duration effects.Diabetol Metab Syndr · PMID 40616152
  29. Effect of oral DHEA on serum testosterone and adaptations to resistance training in young menJ Appl Physiol · PMID 10601178
  30. Effects of short-term dehydroepiandrosterone supplementation on body composition in young athletesChin J Physiol · PMID 21789881
  31. Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval trainingEur J Appl Physiol · PMID 23417481
  32. Dehydroepiandrosterone supplementation and bone turnover in middle-aged to elderly menJ Clin Endocrinol Metab · PMID 11932279
  33. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on boneAm J Clin Nutr · PMID 19321570
  34. A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA supplementation of bone mineral density in healthy adults.Gynecol Endocrinol · PMID 31237150
  35. Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairmentGeriatr Gerontol Int · PMID 20497239
  36. Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: the DHEA and Well-Ness (DAWN) TrialJ Am Geriatr Soc · PMID 18482290
  37. Dhea supplementation and cognition in postmenopausal womenInt J Neurosci · PMID 16393880
  38. Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalismJ Endocrinol Invest · PMID 15636426
  39. Androgens and sexual function: a placebo-controlled, randomized, double-blind study of testosterone vs. dehydroepiandrosterone in men with sexual dysfunction and androgen deficiencyAging Male · PMID 19883295
  40. A randomized controlled trial of dehydroepiandrosterone in postmenopausal women with fibromyalgiaJ Rheumatol · PMID 15996074
  41. Dehydroepiandrosterone (DHEA) effects on HIV replication and host immunity: a randomized placebo-controlled studyAIDS Res Hum Retroviruses · PMID 17263636
  42. Effects of dehydroepiandrosterone supplementation during stressful military training: a randomized, controlled, double-blind field studyStress · PMID 21790446
  43. Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective studyHum Reprod · PMID 20729538
  44. A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials.Exp Gerontol · PMID 33045358
  45. Value of VLCD supplementation with medium chain triglyceridesInt J Obes Relat Metab Disord · PMID 11571605
  46. Components of total energy expenditure in healthy young women are not affected after 14 days of feeding with medium-versus long-chain triglyceridesObes Res · PMID 10348498
  47. Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trialsJ Acad Nutr Diet · PMID 25636220
  48. Effects of dietary medium-chain triglyceride on weight loss and insulin sensitivity in a group of moderately overweight free-living type 2 diabetic Chinese subjectsMetabolism · PMID 17570262
  49. The impact of medium-chain triglycerides on weight loss and metabolic health in individuals with overweight or obesity: A systematic review and meta-analysisPMID 38936302
  50. Effect of Continuous Ingestion of 2 g of Medium-Chain Triglycerides on Substrate Metabolism during Low-Intensity Physical ActivityPMID 35276897
  51. Short-Term Ingestion of Medium-Chain Triglycerides Could Enhance Postprandial Consumption of Ingested Fat in Individuals with a Body Mass Index from 25 to Less than 30: A Randomized, Placebo-Controlled, Double-Blind Crossover StudyPMID 35268094
  52. A systematic review and meta-analysis of medium-chain triglycerides effects on acute satiety and food intakeCrit Rev Food Sci Nutr · PMID 32212947
  53. Enhanced postprandial energy expenditure with medium-chain fatty acid feeding is attenuated after 14 d in premenopausal womenAm J Clin Nutr · PMID 10232626
  54. Endogenous fat oxidation during medium chain versus long chain triglyceride feeding in healthy womenInt J Obes Relat Metab Disord · PMID 11033985
  55. Medium Chain Triglycerides induce mild ketosis and may improve cognition in Alzheimer's disease. A systematic review and meta-analysis of human studiesAgeing Res Rev · PMID 31870908
  56. Medium-chain fatty acids for the prevention or treatment of Alzheimer's disease: a systematic review and meta-analysisNutr Rev · PMID 36633304
  57. Medium-Chain Triglycerides (MCTs) for the Symptomatic Treatment of Dementia-Related Diseases: A Systematic Review.J Nutr Metab · PMID 38715705
  58. Medium-chain triglycerides (8:0 and 10:0) increase muscle mass and function in frail older adults: a combined data analysis of clinical trialsFront Nutr · PMID 38111605
  59. A Randomized, Double-Blind, Controlled Trial Assessing If Medium-Chain Triglycerides in Combination with Moderate-Intensity Exercise Increase Muscle Strength in Healthy Middle-Aged and Older AdultsNutrients · PMID 37513691
  60. Medium-chain triglycerides (8:0 and 10:0) are promising nutrients for sarcopenia: a randomized controlled trialAm J Clin Nutr · PMID 31334544
  61. Effects of selected dietary supplements on migraine prophylaxis: A systematic review and dose-response meta-analysis of randomized controlled trials.Neurol Sci · PMID 39404918
  62. Safety, tolerability, and efficacy of orally administered cannabinoids in MSNeurology · PMID 12011290
  63. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trialCMAJ · PMID 22586334
  64. The effect of cannabis on tremor in patients with multiple sclerosisNeurology · PMID 15079008
  65. Supplementation with vitamin D or ω-3 fatty acids in adolescent girls and young women with endometriosis (SAGE): a double-blind, randomized, placebo-controlled trialAm J Clin Nutr · PMID 32453393
  66. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs)Thorax · PMID 25724847
  67. Vitamin D Supplementation and the Risk of Colds in Patients with AsthmaAm J Respir Crit Care Med · PMID 26540136
  68. Association between prenatal vitamin D supplementation and respiratory diseases in children: a systematic review and meta-analysis.BMC Pediatr · PMID 41204244
  69. Vitamin D supplementation decrease asthma exacerbations in children: a systematic review and meta-analysis of randomized controlled trials.Ann Med · PMID 39421966
  70. The effects of prenatal vitamin D supplementation on respiratory and allergy-related outcomes in children: A systematic review and meta-analysis of randomized controlled trials.World Allergy Organ J · PMID 40535465
  71. Effects of Vitamin D on Endometriosis-Related Pain: A Double-Blind Clinical TrialMed Sci Monit · PMID 27986972
  72. The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosisGynecol Endocrinol · PMID 33508990
  73. Vitamin D for primary dysmenorrhea and endometriosis-related pain - A systematic review of registered RCTs.PLoS One · PMID 40257970
  74. High-Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long-Term Care Residents: A Randomized Clinical TrialJ Am Geriatr Soc · PMID 27861708
  75. Randomized trial of vitamin D supplementation and risk of acute respiratory infection in MongoliaPediatrics · PMID 22908115
  76. Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trialActa Paediatr · PMID 25283480
  77. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysisHealth Technol Assess · PMID 30675873
  78. Therapeutic effect of vitamin D3 in multiple sclerosis patientsImmunol Invest · PMID 21542721
  79. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trialMult Scler · PMID 22354743
  80. Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementationTher Adv Neurol Disord · PMID 22783368
  81. Randomized trial of daily high-dose vitamin D 3 in patients with RRMS receiving subcutaneous interferon β-1aNeurology · PMID 31594857
  82. Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE)Neurol Neuroimmunol Neuroinflamm · PMID 31454777
  83. Effects of adjunct low-dose vitamin d on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trialMult Scler Int · PMID 22567287
  84. Vitamin D supplementation and upper respiratory tract infections in adolescent swimmers: a randomized controlled trialPediatr Exerc Sci · PMID 25050610
  85. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trialJAMA · PMID 23032549
  86. Vitamin D3 and gargling for the prevention of upper respiratory tract infections: a randomized controlled trialBMC Infect Dis · PMID 24885201
  87. Intake of 25-Hydroxyvitamin D3 Reduces Duration and Severity of Upper Respiratory Tract Infection: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Comparison StudyJ Nutr Health Aging · PMID 29582888
  88. Vitamin D₃ Supplementation Reduces the Symptoms of Upper Respiratory Tract Infection during Winter Training in Vitamin D-Insufficient Taekwondo Athletes: A Randomized Controlled TrialInt J Environ Res Public Health · PMID 30223447
  89. A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infectionsEpidemiol Infect · PMID 19296870
  90. Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blinded trial among young Finnish menJ Infect Dis · PMID 20632889
  91. Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy ChildrenJAMA · PMID 28719693
  92. Vitamin D supplementation to prevent infections: a sub-study of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438)Age Ageing · PMID 17702768
  93. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trialClin Infect Dis · PMID 24014734
  94. Effect of monthly high-dose vitamin D supplementation on acute respiratory infections in older adults: A randomized controlled trialClin Infect Dis · PMID 31420647
  95. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention studyBMJ Open · PMID 23242238
  96. Effect of Vitamin D supplementation to reduce respiratory infections in children and adolescents in Vietnam: A randomized controlled trialInfluenza Other Respir Viruses · PMID 30328294
  97. Winter cholecalciferol supplementation at 55°N has little effect on markers of innate immune defense in healthy children aged 4-8 years: a secondary analysis from a randomized controlled trialEur J Nutr · PMID 29572676
  98. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markersAm J Clin Nutr · PMID 19321573
  99. Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adultsNutr Metab · PMID 22405472
  100. Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trialAm J Clin Nutr · PMID 22760564

Supplement stack for Frailty