// Evidence Grader

Claim grades, A through F

Every major claim in this course gets a transparent grade. Use this dashboard to audit what's established, what's preliminary, and what's hype.

A
Clinically established
B
Supported, context-specific
C
Promising, preliminary
D
Plausible, unproven
E
Popular, weak support
F
Misleading or false
A
Folic acid supplementation periconceptionally reduces neural tube defects
Established (MRC 1991, public-health mandate).
Module 01 · Why Supplements Matter — Honest Framing
A
Vitamin D corrects deficiency states and is required for some treatments (e.g., osteoporosis)
Established for deficiency; population-wide prevention claims are weaker.
Module 01 · Why Supplements Matter — Honest Framing
F
Multivitamins prevent cardiovascular disease in well-nourished adults
PHS II, COSMOS — no CV benefit.
Module 01 · Why Supplements Matter — Honest Framing
E
Vitamin C prevents the common cold in the general population
Cochrane: no prevention; small reduction in duration only.
Module 01 · Why Supplements Matter — Honest Framing
F
High-dose antioxidants reduce cancer in smokers
Beta-carotene increased lung cancer (ATBC, CARET).
Module 01 · Why Supplements Matter — Honest Framing
A
Creatine monohydrate improves resistance-training outcomes
Most-studied ergogenic supplement; consistent benefit.
Module 01 · Why Supplements Matter — Honest Framing
A
USP Verified guarantees the product is identity-correct, potent, and contaminant-screened
USP audits formulation, identity, potency, and contaminants.
Module 02 · Regulation: DSHEA, GMP & Third-Party Testing
F
USP/NSF seals prove a supplement is clinically effective
Third-party seals do not test efficacy.
Module 02 · Regulation: DSHEA, GMP & Third-Party Testing
A
Adulteration with sildenafil/tadalafil analogs occurs in 'natural' sexual-enhancement supplements
Documented repeatedly in FDA recalls and analytical studies.
Module 02 · Regulation: DSHEA, GMP & Third-Party Testing
F
Structure-function claims require RCT support
They explicitly do not; they require notification and a disclaimer.
Module 02 · Regulation: DSHEA, GMP & Third-Party Testing
A
GRADE is the dominant guideline-methodology framework
Used by WHO, NICE, USPSTF, ACP.
Module 03 · Evidence Tiers — From DRI to RCTs to Influencers
F
Surrogate outcomes reliably predict hard outcomes for supplements
Repeatedly refuted.
Module 03 · Evidence Tiers — From DRI to RCTs to Influencers
B
Industry funding biases supplement-trial conclusions
Documented in multiple bibliometric reviews.
Module 03 · Evidence Tiers — From DRI to RCTs to Influencers
A
Heme iron is better absorbed than non-heme iron
~15–35% vs 2–20%; less affected by phytate.
Module 04 · Pharmacology of Oral Supplements
B
Vitamin D should be taken with a fat-containing meal
Increases AUC modestly; consistent timing matters more for adherence.
Module 04 · Pharmacology of Oral Supplements
D
Liposomal vitamin C is several-fold more bioavailable than ascorbic acid
Pilot data only; not consistently shown in larger studies.
Module 04 · Pharmacology of Oral Supplements
B
Vitamin D supplementation reduces fractures in deficient older adults with calcium
Modest benefit when combined with Ca²⁺ and baseline deficiency.
Module 05 · Fat-Soluble Vitamins — A, D, E, K
F
Vitamin E supplementation reduces cardiovascular events
HOPE, GISSI-Prevenzione, HPS negative.
Module 05 · Fat-Soluble Vitamins — A, D, E, K
A
Vitamin A supplementation reduces childhood mortality in deficient populations
Established in WHO-endorsed programs.
Module 05 · Fat-Soluble Vitamins — A, D, E, K
D
Vitamin K2 (MK-7) reverses arterial calcification
Preclinical and small trials; insufficient.
Module 05 · Fat-Soluble Vitamins — A, D, E, K
A
Periconceptional folic acid prevents NTDs
MRC 1991 + global fortification programs.
Module 06 · Water-Soluble Vitamins — B-complex & C
F
IV vitamin C cures sepsis
CITRIS-ALI and LOVIT trials negative or harmful.
Module 06 · Water-Soluble Vitamins — B-complex & C
A
Chronic high-dose B6 causes sensory neuropathy
Established >200 mg/d chronic.
Module 06 · Water-Soluble Vitamins — B-complex & C
B
Oral iron alternate-day matches daily for repletion with better tolerance
Stoffel/Moretti 2017.
Module 07 · Minerals — Iron, Zinc, Magnesium, Calcium, Selenium
D
Calcium supplementation reduces fractures in community-dwelling adults
WHI and meta-analyses largely null.
Module 07 · Minerals — Iron, Zinc, Magnesium, Calcium, Selenium
B
Magnesium 400–600 mg/d reduces migraine frequency
AAN/AHS Level B.
Module 07 · Minerals — Iron, Zinc, Magnesium, Calcium, Selenium
F
Selenium supplementation prevents cancer in selenium-replete populations
SELECT negative.
Module 07 · Minerals — Iron, Zinc, Magnesium, Calcium, Selenium
A
Icosapent ethyl 4 g/d reduces MACE in secondary prevention
REDUCE-IT (caveat: mineral oil placebo).
Module 08 · Omega-3 Fatty Acids — EPA, DHA & the AF Signal
F
OTC fish oil prevents primary CV events in well-treated patients
VITAL, ASCEND, OMEMI.
Module 08 · Omega-3 Fatty Acids — EPA, DHA & the AF Signal
B
EPA ≥1 g/d as adjunct in unipolar depression provides modest benefit
Meta-analyses positive but heterogeneous.
Module 08 · Omega-3 Fatty Acids — EPA, DHA & the AF Signal
B
S. boulardii reduces antibiotic-associated diarrhea
Meta-analyses positive.
Module 09 · Probiotics & the Gut — Strain-Specific Reality
F
Probiotics improve outcomes in severe acute pancreatitis
PROPATRIA — increased mortality.
Module 09 · Probiotics & the Gut — Strain-Specific Reality
E
Generic 'probiotic yogurt' improves immune function
Strain/dose typically inadequate.
Module 09 · Probiotics & the Gut — Strain-Specific Reality
B
St John's Wort has RCT evidence for mild-moderate depression
Comparable to SSRI in some trials.
Module 10 · Herbals & Botanicals — Curcumin, St John's Wort, Ashwagandha
A
St John's Wort induces CYP3A4 and P-gp clinically
Extensively documented.
Module 10 · Herbals & Botanicals — Curcumin, St John's Wort, Ashwagandha
B
Curcumin with enhanced bioavailability formulations has caused DILI
LiverTox case series.
Module 10 · Herbals & Botanicals — Curcumin, St John's Wort, Ashwagandha
F
Ashwagandha is safe in pregnancy
Animal teratogenicity, contraindicated.
Module 10 · Herbals & Botanicals — Curcumin, St John's Wort, Ashwagandha
A
Creatine monohydrate 3–5 g/d improves strength and lean mass with resistance training
Most-studied ergogenic.
Module 11 · Performance & Cognition — Creatine, Caffeine, Nootropics
A
Caffeine 3–6 mg/kg improves endurance/strength acutely
Consistent.
Module 11 · Performance & Cognition — Creatine, Caffeine, Nootropics
E
Generic 'nootropic stack' improves cognition long-term
No RCT for most products.
Module 11 · Performance & Cognition — Creatine, Caffeine, Nootropics
A
SJW reduces tacrolimus, OCP, and protease inhibitor exposure
Established and clinically dangerous.
Module 12 · Drug-Supplement Interactions & Clinical Counseling
C
Stopping fish oil 7 days pre-op reduces bleeding
Bleeding-time effect modest; some surgeons require.
Module 12 · Drug-Supplement Interactions & Clinical Counseling
B
5-HTP combined with SSRI may precipitate serotonin syndrome
Mechanistically plausible; case reports.
Module 12 · Drug-Supplement Interactions & Clinical Counseling
// Supplement evidence map · companion to claim grades

Where supplements sit on the evidence map

Use the A–F grade above for individual claims; use these five tiers when judging a whole supplement category. Remember: in the US, no dietary supplement is FDA-approved for safety or efficacy under DSHEA — these tiers reflect human evidence, not regulatory blessing.

  1. Tier 1
    Deficiency rescue or guideline-endorsed
    Replaces a documented deficiency or is in major guidelines (e.g., folate in pregnancy, B12 in deficiency, vitamin D in osteoporosis regimens, iron in IDA).
    e.g. Folic acid (NTD prevention), B12 (deficiency), iron (IDA), oral rehydration
  2. Tier 2
    Supported by multiple RCTs in specific populations
    Reasonable evidence in a defined population or indication; effect size usually small-to-moderate.
    e.g. Omega-3 EPA (REDUCE-IT), creatine monohydrate (strength/power), melatonin (jet lag, DSPS)
  3. Tier 3
    Mixed or modest RCT evidence
    Some positive trials, some null; signal is real but small or inconsistent. Often population-dependent.
    e.g. Magnesium (migraine, sleep), curcumin (OA), zinc lozenges (common cold duration)
  4. Tier 4
    Plausible mechanism, weak human evidence
    Preclinical or pilot human data; marketing far outpaces the evidence base.
    e.g. Most adaptogens, ashwagandha (anxiety), berberine (glucose), NMN/NR (longevity)
  5. Tier 5
    Marketing-led, weak or negative evidence
    Popular consumer claims with no robust trials, or where trials are negative (or show harm in some populations).
    e.g. Mega-dose antioxidants (SELECT), 'detox' products, most weight-loss stacks, colloidal silver
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