FFFPLAN 3.0 · THE EVIDENCE
THE SCIENCE
BEHIND THE STACK.
What the research found. Who it studied. What it means for your supplements.
Before you readA positive study is not a guaranteed benefit.
This is a selected research guide, not a systematic review or an instruction to take every supplement. Studies involving both women and men were prioritised where available.
Result labels describe each paper’s findings, not the overall certainty of a supplement’s benefits. “Positive” means a benefit on at least one studied measure. “Mixed” means results varied. “Preliminary” means the evidence needs particular caution. A negative result applies to the population and intervention tested.
Research doses are shown for comparison, not as recommendations. Brand, ingredient form, dose, nutrient status and health conditions affect how well a finding applies. The methylfolate review includes existing trials, so 34 papers does not mean 34 independent experiments.
Expand a paper to see participants, the intervention, findings and limitations. Original-paper links open in a new tab.
Electrolytes
PowerBar 5 Electrolytes
Hydration
Electrolytes can help retain fluid, particularly when replacing sweat losses.
01Pence & Bloomer · 2020 · NutrientsElectrolyte tablets and fluid balancePositive
- Who took part
- 18 adults · women and men
- What was studied
- Nuun tablets in water; fluid balance measured over 4 hours
What the researchers found
Electrolyte tablets improved fluid retention compared with water.
Keep in mind
Relevant tablet-based research, but a different brand and formulation.
02Ray et al. · 1998 · Journal of Applied PhysiologySodium in rehydration drinks and mealsPositive
- Who took part
- 30 adults · 15 women, 15 men
- What was studied
- Rehydration after exercise-induced loss of 2.5% body weight
What the researchers found
Sodium-rich drinks and meals improved fluid retention and restoration of plasma volume.
Keep in mind
Protein, carbohydrate and other ingredients also differed between drinks.
03Maughan & Leiper · 1995 · European Journal of Applied PhysiologySodium and post-exercise rehydrationPositive
- Who took part
- 6 adults · men only
- What was studied
- Drinks with different sodium concentrations after exercise-induced dehydration
What the researchers found
Higher sodium concentrations increased the proportion of fluid retained.
Keep in mind
Very small trial in dehydrated men; not evidence for routine morning use.
How to read this: These studies tested sodium-containing drinks or Nuun tablets, not PowerBar. They do not establish that everyone needs electrolytes every morning.
Vitamin C
Ascorbic acid
Tissue repair · immune-related outcomes
The selected trials suggest benefits for wound healing and for people with low vitamin-C status.
01Pisalsitsakul et al. · 2022 · International Journal of DentistryVitamin C and tooth-extraction wound healingPositive
- Who took part
- 32 participants · 19 female, 13 male · ages 14–28
- What was studied
- 600 mg/day in three doses; also tested higher-dose comparisons
What the researchers found
600 mg/day improved one measure of extraction-wound closure versus placebo.
Keep in mind
Small trial; higher-dose comparisons did not show the same significant improvement.
02Gunton et al. · 2021 · British Journal of NutritionVitamin C and foot-ulcer healingPreliminary
- Who took part
- 16 people with foot ulcers
- What was studied
- 500 mg/day; healing assessed at 8 weeks
What the researchers found
The vitamin-C group had better ulcer healing. Half of participants were deficient at baseline.
Keep in mind
Deficient participants were offered vitamin C after 4 weeks, complicating comparison. Very small sample.
03Johnston et al. · 2014 · NutrientsVitamin C and common-cold incidencePositive
- Who took part
- Men with marginal vitamin-C status
- What was studied
- 1,000 mg/day for 8 weeks
What the researchers found
Fewer participants reported colds with vitamin C than with placebo.
Keep in mind
The apparent reduction in cold duration did not reach statistical significance. Not proof of universal infection prevention.
How to read this: A benefit in deficiency or impaired healing does not mean additional vitamin C improves health in everyone.
B-vitamin complex
Methylated formulation
Mood · mental energy · brain health
Some B-vitamin combinations improved selected stress, mood or brain-imaging measures.
01Stough et al. · 2011 · Human PsychopharmacologyB-complex supplementation and work stressMixed
- Who took part
- Women and men · 60 completed
- What was studied
- High-dose B-vitamin multivitamins for 90 days
What the researchers found
Participants reported less personal strain, confusion and depressed/dejected mood on selected measures.
Keep in mind
Other mood and anxiety measures did not improve. Tested multivitamin formulations.
02Kennedy et al. · 2010 · PsychopharmacologyB vitamins, mood and mental performancePositive
- Who took part
- 215 adults · men only
- What was studied
- B-complex plus vitamin C and minerals for 33 days
What the researchers found
The combination improved perceived stress, vigour and mental tiredness.
Keep in mind
Effects cannot be attributed to B vitamins alone or to methylated forms.
03Smith et al. · 2010 · PLOS ONEB vitamins and brain atrophy in mild cognitive impairmentPositive
- Who took part
- Older women and men with mild cognitive impairment
- What was studied
- B6, B12 and folic acid for 2 years
What the researchers found
The combination slowed brain-volume loss, particularly with higher baseline homocysteine.
Keep in mind
An imaging outcome in a selected population; not proof that a methylated complex improves cognition in everyone.
How to read this: These papers do not establish that methylated formulations outperform conventional B vitamins. None validates the exact client product.
Methylfolate
L-methylfolate
Depression-related mood outcomes
The clearest evidence concerns adding methylfolate to treatment for depression.
01Papakostas et al. · 2012 · American Journal of PsychiatryL-methylfolate added to antidepressantsMixed
- Who took part
- Women and men with SSRI-resistant depression · trials of 148 and 75
- What was studied
- Two trials; the positive trial used 15 mg/day alongside an SSRI
What the researchers found
The first trial was negative. The second found improved depression outcomes at 15 mg/day.
Keep in mind
Specific to patients with an inadequate antidepressant response; not general mood regulation.
02Godfrey et al. · 1990 · The LancetMethylfolate and recovery from psychiatric illnessPositive
- Who took part
- 41 women and men with depression or schizophrenia and low folate status
- What was studied
- 15 mg/day for 6 months alongside usual treatment
What the researchers found
Clinical and social recovery improved compared with placebo.
Keep in mind
Small, selected clinical population with borderline or definite folate deficiency.
03Al Maruf et al. · 2022 · PharmacopsychiatryL-methylfolate augmentation: systematic review and meta-analysisModest benefit
- Who took part
- Adults with depressive disorders across several studies
- What was studied
- Review of existing studies; not a new intervention
What the researchers found
Adding methylfolate to antidepressants showed a modest overall improvement in depression outcomes.
Keep in mind
Includes overlapping evidence from existing trials. Do not count it as an independent clinical trial.
How to read this: These studies do not establish routine anxiety reduction or mood enhancement in healthy clients. The clinical doses were used alongside psychiatric treatment.
L-theanine
Morning and evening ingredient
Relaxation · anxiety · sleep
Small studies suggest relaxation and sleep benefits; evidence for treating an anxiety disorder is less convincing.
01Hidese et al. · 2019 · NutrientsStress-related symptoms and sleepPreliminary
- Who took part
- 30 adults · 21 women, 9 men
- What was studied
- 200 mg/day for 4 weeks; crossover trial
What the researchers found
Selected self-reported sleep measures improved versus placebo, including time to fall asleep and disturbances.
Keep in mind
Small trial; does not establish treatment of an anxiety disorder.
02Evans et al. · 2021 · Neurology and TherapyA single dose during an acute stress challengePositive
- Who took part
- Women and men with moderate stress
- What was studied
- Single 200 mg dose during a mental-arithmetic stress challenge
What the researchers found
EEG alpha activity increased and selected stress-response measures improved.
Keep in mind
Brainwave changes are consistent with relaxation, but do not prove lasting anxiety relief.
03Sarris et al. · 2019 · Journal of Psychiatric ResearchL-theanine for generalised anxiety disorderMixed
- Who took part
- 46 women and men taking antidepressants
- What was studied
- 450–900 mg/day alongside stable antidepressant treatment
What the researchers found
No advantage for the main anxiety outcome or overall insomnia severity; sleep satisfaction improved on a secondary measure.
Keep in mind
This trial does not support L-theanine as an effective treatment for generalised anxiety disorder.
How to read this: The studies below do not validate a particular morning-plus-evening capsule schedule.
Lion’s Mane
Hericium erinaceus
Cognition · memory · brain fog
Human research is early and mixed. Some cognitive-test improvements have been observed, but a general memory benefit is unproven.
01Mori et al. · 2009 · Phytotherapy ResearchLion’s Mane and mild cognitive impairmentPreliminary
- Who took part
- 30 women and men · ages 50–80
- What was studied
- Approximately 3 g/day mushroom-powder tablets for 16 weeks
What the researchers found
Cognitive-test scores improved; scores declined after supplementation stopped.
Keep in mind
Small study in mild cognitive impairment, rather than everyday brain fog.
02Docherty et al. · 2023 · NutrientsCognition, stress and mood in young adultsMixed
- Who took part
- Young women and men · 43 in the acute analysis
- What was studied
- 1.8 g/day; acute assessments and 28-day supplementation
What the researchers found
Response speed improved on one task, while other findings were null or negative, including poorer immediate word recall acutely.
Keep in mind
Small pilot with multiple outcomes; not evidence of a general memory boost.
03Surendran et al. · 2025 · Frontiers in NutritionAcute effects on cognition and moodNo overall benefit
- Who took part
- 18 adults · 8 women, 10 men
- What was studied
- Single dose of a standardised extract
What the researchers found
Overall cognitive performance and mood did not significantly improve versus placebo.
Keep in mind
An acute study cannot determine whether longer-term supplementation helps.
How to read this: Mushroom powders and extracts vary. These studies do not demonstrate that two unspecified capsules remove brain fog.
Omega-3
EPA and DHA
Inflammation · recovery
Selected trials found lower inflammatory markers. Evidence for exercise recovery is more preliminary.
01Kiecolt-Glaser et al. · 2012 · Brain, Behavior, and ImmunityInflammation in middle-aged and older adultsPositive
- Who took part
- 138 women and men · sedentary and overweight
- What was studied
- 1.25 or 2.5 g/day omega-3 for 4 months
What the researchers found
Inflammatory markers fell relative to placebo.
Keep in mind
Changes in blood markers do not automatically mean improved symptoms.
02Kiecolt-Glaser et al. · 2011 · Brain, Behavior, and ImmunityInflammation in medical studentsPositive
- Who took part
- 68 medical students · women and men
- What was studied
- Approximately 2.5 g/day for 12 weeks
What the researchers found
Stimulated production of the inflammatory signal IL-6 fell; anxiety symptoms also decreased.
Keep in mind
A specific immune-response measure in a small, selected population.
03Jouris et al. · 2011 · Journal of Sports Science and MedicineOmega-3 and exercise-induced sorenessPreliminary
- Who took part
- 11 adults · women and men
- What was studied
- 3 g/day for 7 days after a control period
What the researchers found
Participants reported less soreness after eccentric exercise in the supplementation phase.
Keep in mind
Very small fixed-order study without a randomised placebo comparison. Adaptation to repeat exercise could explain some benefit.
How to read this: Compare the amount of EPA and DHA, not simply the number of capsules or total fish-oil weight.
Glucosamine + chondroitin + MSM
Joint complex
Joint pain · physical function
Some trials found better joint symptoms, while a large trial of glucosamine and chondroitin was negative overall.
01Lubis et al. · 2017 · Acta Medica IndonesianaGlucosamine–chondroitin with and without MSMPositive
- Who took part
- 147 people with mild knee osteoarthritis
- What was studied
- 1,500 mg glucosamine + 1,200 mg chondroitin + 500 mg MSM daily for 12 weeks
What the researchers found
The three-ingredient combination improved clinical symptoms versus glucosamine–chondroitin and placebo.
Keep in mind
The closest formulation match; specific to mild knee osteoarthritis, not cartilage regeneration.
02Clegg et al. · 2006 · New England Journal of MedicineGAIT: glucosamine and chondroitin for knee painNo overall benefit
- Who took part
- 1,583 adults · women and men with knee osteoarthritis
- What was studied
- Glucosamine, chondroitin, their combination or controls for 24 weeks
What the researchers found
Glucosamine, chondroitin and their combination did not significantly outperform placebo for the primary pain response overall.
Keep in mind
MSM was not included; results cannot directly settle the three-ingredient combination.
03Kim et al. · 2006 · Osteoarthritis and CartilageMSM for knee osteoarthritisPreliminary
- Who took part
- 50 women and men · ages 40–76
- What was studied
- 6 g/day MSM for 12 weeks
What the researchers found
Pain and physical function improved, but not all symptom measures.
Keep in mind
Small pilot; tested MSM alone at a higher dose than many combination products contain.
How to read this: Symptom improvement is not evidence of cartilage rebuilding. These studies focus on knee osteoarthritis.
Vitamin D3 + K2
Cholecalciferol + menaquinone
Bone health
Bone benefits depend on the population and combination studied. Adding K2 has not consistently improved bone outcomes.
01Chapuy et al. · 1992 · New England Journal of MedicineD3, calcium and fracture preventionPositive
- Who took part
- 3,270 older women · average age 84
- What was studied
- 800 IU/day D3 + 1,200 mg calcium for 18 months
What the researchers found
Hip and other nonvertebral fractures were reduced.
Keep in mind
Cannot isolate D3 from calcium; K2 was not tested. Findings concern an older population.
02Knapen et al. · 2013 · Osteoporosis InternationalThree years of vitamin K2Positive
- Who took part
- 244 postmenopausal women
- What was studied
- 180 µg/day MK-7 for 3 years
What the researchers found
Bone loss slowed at the lumbar spine and femoral neck.
Keep in mind
Selected bone measures improved; this does not establish fracture prevention.
03Rønn et al. · 2021 · Osteoporosis InternationalK2 added to D3 and calciumNo added benefit
- Who took part
- 142 postmenopausal women with osteopenia
- What was studied
- 375 µg/day MK-7 for 3 years; D3 and calcium in both groups
What the researchers found
A bone-protein marker improved, but bone density and microarchitecture did not improve versus the comparison group.
Keep in mind
A particularly relevant combination study; biochemical changes did not translate into better bone structure.
04LeBoff et al. · 2022 · New England Journal of MedicineVITAL: vitamin D and fracturesNo overall benefit
- Who took part
- 25,871 adults · approximately half women
- What was studied
- 2,000 IU/day D3; median follow-up 5.3 years
What the researchers found
Supplementation did not reduce fractures in this broadly healthy population.
Keep in mind
Participants were not selected for vitamin-D deficiency or osteoporosis.
How to read this: The positive D3/calcium study and the broadly healthy VITAL population answer different questions. Neither tests your exact D3+K2 capsule.
Magnesium bisglycinate
Magnesium glycinate
Sleep quality
An exact-form study found a small improvement in insomnia symptoms. Other magnesium trials have produced mixed results.
01Schuster et al. · 2025 · Nature and Science of SleepMagnesium bisglycinate and poor sleepModest benefit
- Who took part
- 155 adults · women and men · ages 18–65
- What was studied
- 250 mg/day elemental magnesium as bisglycinate for 4 weeks
What the researchers found
Insomnia-severity scores improved slightly more than with placebo.
Keep in mind
Small effect; other psychological outcomes did not significantly improve. Exact magnesium form match.
02Abbasi et al. · 2012 · Journal of Research in Medical SciencesMagnesium and primary insomniaPositive
- Who took part
- 46 older adults with insomnia
- What was studied
- 500 mg/day elemental magnesium as oxide for 8 weeks
What the researchers found
Several self-reported insomnia measures improved versus placebo.
Keep in mind
Small trial using magnesium oxide, not bisglycinate.
03Nielsen et al. · 2010 · Magnesium ResearchMagnesium status and poor sleepNo clear advantage
- Who took part
- 100 adults · 78 women, 22 men
- What was studied
- 320 mg/day magnesium as citrate for 7 weeks
What the researchers found
Sleep scores improved in both groups without a demonstrated magnesium-specific advantage.
Keep in mind
Different magnesium form; the study did not establish a sleep benefit over placebo.
How to read this: Elemental magnesium is the relevant dose. Magnesium oxide and citrate are different formulations from bisglycinate.
Zinc picolinate
Zinc
Immune function · DNA integrity
Zinc trials show benefits for selected immune and DNA measures, especially where zinc status or intake is low.
01Prasad et al. · 2007 · American Journal of Clinical NutritionZinc supplementation and infectionsPositive
- Who took part
- 50 older adults · women and men
- What was studied
- 45 mg/day elemental zinc as gluconate for 12 months
What the researchers found
Infection incidence was lower than with placebo.
Keep in mind
Evidence for zinc in an older population; not a picolinate study or a routine-dose recommendation.
02Barnett et al. · 2016 · American Journal of Clinical NutritionZinc and T-cell responsesPositive
- Who took part
- 31 zinc-deficient nursing-home residents
- What was studied
- 30 mg/day zinc as gluconate versus 5 mg/day control for 3 months
What the researchers found
Zinc status, T-cell numbers and measured proliferation improved.
Keep in mind
Immune-cell outcomes; the study did not directly establish fewer infections.
03Joray et al. · 2015 · Nutrition ResearchZinc and DNA strand breaksPositive
- Who took part
- 40 Ethiopian women with diets low in bioavailable zinc
- What was studied
- 20 mg/day zinc as sulfate for 17 days
What the researchers found
Measured DNA strand breaks decreased in supplemented participants.
Keep in mind
A biomarker finding in a specific population; not proof of broadly enhanced DNA repair in zinc-replete clients.
How to read this: These studies used gluconate or sulfate, not picolinate. They do not establish a special picolinate benefit or improved sleep.