Skip to main content

WhatIsBrainFog.com - Drug-Supplement Interaction Reference

Printed from: whatisbrainfog.com/drug-interactions/

← Back to Home
Safety Reference

Drug-Supplement Interactions & Medication Audit

Check every supplement against your medications before starting. Review this chart with your physician or pharmacist.

75 supplement interactions · 19 fog-causing medications · 51 medication profiles with CYP data. Cross-check with Drugs.com, Examine.com, or your pharmacist.

How to use this page

  • Taking a supplement? → Check Table 1 to see what medications it conflicts with
  • On a medication? → Check Table 3 to see which supplements you need to time, adjust, or avoid
  • Experiencing brain fog? → Check Table 2 to see if your medication is a known cause
  • Typically, verify with your pharmacist before starting a new supplement on any prescription medication
AVOID Avoid this combination
HIGH Serious risk, separate timing
MODERATE Time apart, monitor
LOW Monitor only

Table 1: Supplement-Drug Interactions

5-HTP AVOID

Do NOT combine with:

SSRIs, SNRIs, MAOIs, Tramadol, Triptans

Serotonin syndrome - potentially fatal. Case report: serotonin syndrome from sertraline + 5-HTP supplement led to rhabdomyolysis and acute compartment syndrome

Timing: Take evening, with food

PMC5580516 (case report: SSRI + 5-HTP → serotonin syndrome → rhabdomyolysis); PMC6184959 (serotonin toxicity review)

St. John's Wort AVOID

Do NOT combine with:

SSRIs, birth control, blood thinners, cyclosporine

Potent CYP3A4 inducer (degree correlates with hyperforin content). Reduces drug levels of cyclosporine, birth control, anticoagulants. Also causes serotonin syndrome with SSRIs - sertraline and paroxetine most commonly reported

Timing: Take with food. Wash out 2+ weeks

PMC1874438 (clinical outcomes review); PMC2782080 (updated clinical observations); PMID 15260917 (pharmacokinetic interactions); PMC12420457 (SSRI interactions)

Ginkgo Biloba HIGH

Do NOT combine with:

Blood thinners, NSAIDs

Increased bleeding risk. 2025 meta-analysis: OR 1.08 (p<0.001) for bleeding when combined with antiplatelets. Clopidogrel and aspirin showed highest interaction prevalence. However, controlled RCTs show less clear risk than case reports suggest

Timing: Take with food, morning/noon. Stop 2 weeks before surgery

PMID 40198642 (2025 comprehensive analysis, n=1985); PMID 21923430 (systematic review/meta-analysis); PMID 18214851 (antiplatelet interaction review)

NAC HIGH

Do NOT combine with:

Nitroglycerin, activated charcoal

Forms S-nitroso-NAC with nitroglycerin - potentiates vasodilation and headache. Study: headache score tripled (3 vs 1), symptomatic hypotension in 7 vs 0 patients (p=0.006). Side effects 35% with combination vs ~18% with NTG alone

Timing: Empty stomach, separate from nitroglycerin 4+ hours

PMID 1505148 (NAC potentiates NTG headache/arterial response); PMID 3137075 (unstable angina hypotension data); StatPearls NBK537183

Iron HIGH

Do NOT combine with:

Thyroid medication, antibiotics (tetracyclines, quinolones), antacids, levodopa

Chelation reduces absorption of both iron and the co-administered drug. Levothyroxine absorption reduced if taken within 4 hours. Only 31.8% of patients are told to separate; only 40.7% of those comply

Timing: Empty stomach with vitamin C, separate from thyroid 4 hours, antibiotics 2-4 hours

PMC8002057 (levothyroxine-supplement systematic review); NIH ODS iron fact sheet; Drugs.com iron interaction checker

Magnesium MODERATE

Do NOT combine with:

Fluoroquinolones, tetracyclines, bisphosphonates, levothyroxine

Chelation reduces antibiotic and thyroid medication absorption. Same 4-hour separation rule as iron and calcium

Timing: Separate from antibiotics 2+ hours, thyroid medication 4+ hours

PMC8002057 (levothyroxine interaction systematic review); Drugs.com magnesium interaction checker

Omega-3 (high dose) MODERATE

Do NOT combine with:

Blood thinners, pre-surgery

Additive anticoagulant at >3g/day. EPA component has antiplatelet properties. Risk is dose-dependent - standard 1-2g doses have minimal bleeding risk

Timing: With fat-containing meal

PMC9586694 (dietary supplements and bleeding review); Drugs.com omega-3 interaction checker

Vitamin D MODERATE

Do NOT combine with:

Thiazide diuretics, digoxin

Thiazides reduce calcium excretion while vitamin D increases calcium absorption - combined hypercalcemia risk. Hypercalcemia potentiates digoxin toxicity (arrhythmia risk)

Timing: With fat, morning preferred

Drugs.com vitamin D interaction checker; Mayo Clinic vitamin D guidance

Alpha Lipoic Acid MODERATE

Do NOT combine with:

Diabetes medications (insulin, metformin, sulfonylureas)

Additive blood sugar lowering - hypoglycemia risk. 29 known drug interactions on Drugs.com (all minor). Relatively clean interaction profile compared to other supplements

Timing: Empty stomach, 30 min before meals

Drugs.com 29 interactions listed; Examine.com ALA research page

Ashwagandha MODERATE

Do NOT combine with:

Thyroid medications, immunosuppressants, sedatives

Animal studies: increased T4 by ~40%. Case reports of thyroid level changes in humans (2024). May stimulate immune function - opposes immunosuppressants. Additive sedation with CNS depressants

Timing: With food, start low 300mg

NCCIH ashwagandha safety review (2024); GoodRx 5 ashwagandha interactions; Examine.com ashwagandha research

Methylene Blue AVOID

Do NOT combine with:

SSRIs, SNRIs, MAOIs, Tramadol, Buspirone, clomipramine

Potent reversible MAO-A inhibitor at nanomolar concentrations. At least 14 published case reports of serotonin toxicity, 1 fatal. FDA safety communication issued October 2011

Timing: Only pharmaceutical-grade USP, off serotonergic meds 2+ weeks

PMC2078225 (Gillman & Ramsay 2006 - first MAO-A inhibition demonstration); FDA Drug Safety Communication October 2011; PMC11089602

Berberine HIGH

Do NOT combine with:

Metformin, insulin, other diabetes medications

Additive blood sugar lowering - hypoglycemia risk. Berberine may increase metformin levels when taken 2 hours before

Timing: With meals. If on metformin, take at the same time (not 2 hours before)

GoodRx clinical review; PMID 35489323

Curcumin / Turmeric HIGH

Do NOT combine with:

Warfarin, clopidogrel, aspirin, anticoagulants

Antiplatelet effect increases bleeding risk. Case report: INR rose above 10 in a patient on warfarin after starting turmeric

Timing: With fat for absorption. Stop 2 weeks before surgery

PMID 22531131; Medsafe NZ alert 2018

CoQ10 MODERATE

Do NOT combine with:

Warfarin, blood pressure medications

May reduce warfarin effectiveness (structurally similar to vitamin K). May enhance blood pressure medication effects

Timing: With fat-containing meal

PMID 17482884; AHA/ACC guidance

Creatine LOW

Do NOT combine with:

NSAIDs (long-term), diuretics, nephrotoxic drugs

Theoretical kidney stress with nephrotoxic drugs. Dehydration risk with diuretics. May cause false-positive on kidney function tests (elevated creatinine)

Timing: 5g daily with any meal. Stay well-hydrated

Drugs.com interaction checker; DrugBank DB00148

Melatonin MODERATE

Do NOT combine with:

Blood pressure medications, immunosuppressants, sedatives, anticoagulants

Enhances blood pressure lowering (hypotension risk). Stimulates immune function - may counteract immunosuppressants. Additive sedation with CNS depressants

Timing: 30-60 min before bed. Low dose (0.3-1mg) first

Mayo Clinic drug interactions; GoodRx 9 interactions guide

Lion's Mane MODERATE

Do NOT combine with:

Anticoagulants, antiplatelet drugs

Inhibits collagen-induced platelet aggregation - slows blood clotting. Additive bleeding risk with blood thinners

Timing: With food. Stop 2 weeks before surgery

WebMD lion's mane interactions; in vitro platelet studies

Quercetin HIGH

Do NOT combine with:

Cyclosporine, antibiotics (fluoroquinolones), CYP3A4-metabolized drugs

Alters cyclosporine levels (both increases and decreases reported). Inhibits CYP3A4 and P-glycoprotein - may increase levels of many drugs

Timing: On empty stomach. Separate from antibiotics 2+ hours

PMID 21466223; PMC5042751

Probiotics HIGH

Do NOT combine with:

Immunosuppressants (cyclosporine, tacrolimus, azathioprine), chemotherapy

Risk of bacteremia or fungemia in immunocompromised patients. Live organisms can cross gut barrier when immune system is suppressed

Timing: With or after meals. Separate from antibiotics 2+ hours

PMID 26287986; Frontiers in Neuroscience review

Zinc MODERATE

Do NOT combine with:

Fluoroquinolones, tetracyclines, penicillamine, bisphosphonates

Chelation reduces absorption of both zinc and the antibiotic. Reduces penicillamine absorption

Timing: Take 2 hours before or 4-6 hours after antibiotics. Separate from penicillamine 1+ hour

NIH ODS zinc fact sheet; Drugs.com interaction checker

Selenium LOW

Do NOT combine with:

Cisplatin, barbiturates, blood thinners

May reduce cisplatin effectiveness. Additive sedation with barbiturates. Mild anticoagulant effect at high doses

Timing: With food. Do not exceed 400mcg/day

NIH ODS selenium fact sheet; WebMD selenium interactions

Bacopa Monnieri HIGH

Do NOT combine with:

Thyroid medications, amitriptyline, CYP1A2/2C9/2C19/3A4-metabolized drugs

Inhibits CYP1A2, 2C9, 2C19, 3A4. Increases amitriptyline levels in animal studies. May increase thyroid hormone levels (T4 by ~40% in animal models)

Timing: With food. Separate from thyroid medication 4+ hours

PMC6271976; SciELO Brazil amitriptyline study; Examine.com bacopa FAQ

Rhodiola Rosea HIGH

Do NOT combine with:

MAOIs, SSRIs, SNRIs, antihypertensives, CYP2C9/3A4-metabolized drugs

MAO inhibitory activity - serotonin syndrome risk with serotonergic drugs. Potent CYP3A4, CYP2D6, and P-gp inhibition. Additive blood pressure lowering

Timing: Morning with food (stimulating). Avoid evening dosing

PMID 25413939 (case report); PMC9881059; MSKCC rhodiola monograph

Alpha-GPC MODERATE

Do NOT combine with:

Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), scopolamine

Excessive acetylcholine accumulation with AChE inhibitors - GI upset, bradycardia, urinary issues. Opposes scopolamine effects

Timing: With food. Morning or early afternoon (mildly stimulating)

PMID 1662399; ADDF cognitive vitality review

Phosphatidylserine MODERATE

Do NOT combine with:

Anticoagulants (warfarin, heparin), antiplatelet drugs

Enhances heparin anticoagulant effect. Mild anticoagulant properties may increase bleeding risk with blood thinners

Timing: With food. Separate from blood thinners

PMID 7314577; Cleveland Clinic PS monograph; RxList

L-Theanine LOW

Do NOT combine with:

Blood pressure medications, sedatives, benzodiazepines

Additive blood pressure lowering with antihypertensives. Mild additive sedation with CNS depressants

Timing: Any time. 200mg typical dose

WebMD theanine interactions; PMC3518171

Methylfolate (5-MTHF) MODERATE

Do NOT combine with:

Methotrexate, phenytoin, carbamazepine, valproic acid

May reduce methotrexate effectiveness. Anticonvulsants interfere with folate metabolism - may need higher doses. 25 known drug interactions (3 major)

Timing: With food. Morning preferred

Drugs.com 25 interactions; DrugBank DB04789

Vitamin B12 LOW

Do NOT combine with:

Metformin, PPIs (omeprazole), colchicine, chloramphenicol

Not a dangerous interaction - these drugs DEPLETE B12. Metformin impairs B12 absorption. PPIs reduce gastric acid needed for B12 release. Combined metformin + PPI significantly increases deficiency risk

Timing: Sublingual methylcobalamin bypasses absorption issues. Any time of day

PMC3507616; MHRA 2024 guidance; PMID Jung 2025

Vitamin C (high dose) MODERATE

Do NOT combine with:

Warfarin, estrogen/HRT, chemotherapy, aluminum-containing antacids

High doses may reduce warfarin effectiveness. Increases estrogen levels (HRT side effects). May interfere with chemotherapy. Increases aluminum absorption with antacids

Timing: With food. Standard doses (500-1000mg) are generally safe. Risks mainly at >2g/day

PMC11082382; Mayo Clinic vitamin C; GoodRx interactions

Electrolytes / Sodium Loading HIGH

Do NOT combine with:

Lithium, ACE inhibitors, potassium-sparing diuretics

Sodium changes alter lithium clearance - toxicity risk. Potassium supplements + ACE inhibitors + spironolactone = dangerous hyperkalemia (K+ rose 1.2 mmol/L in studies). Sodium loading counters diuretic effects

Timing: Spread throughout day. Monitor if on any cardiac or psychiatric medications

PMID 8521679; PMC4955086; PMC7358048

Acetyl-L-Carnitine (ALCAR) MODERATE

Do NOT combine with:

Warfarin, acenocoumarol, thyroid medications, anticonvulsants

Increases anticoagulant effect of warfarin/acenocoumarol. May decrease thyroid hormone effectiveness. May lower seizure threshold in people with seizure history

Timing: With food. Separate from thyroid medication 4h

WebMD ALCAR interactions; RxList ALCAR precautions; DrugBank DB08842

Saffron MODERATE

Do NOT combine with:

SSRIs/SNRIs (serotonin risk above 100mg/day), anticoagulants, antihypertensives

At 30mg/day: clinical trials show safe with SSRIs. Above 100mg/day: increased serotonergic load. Anticoagulant properties - case report of bleeding with rivaroxaban. Additive blood pressure lowering

Timing: With food. Standard dose 30mg/day standardized extract

PMC11426294 (saffron in depression comparative review); WebMD saffron interactions; rivaroxaban case report

SAMe (S-adenosylmethionine) HIGH

Do NOT combine with:

SSRIs, SNRIs, MAOIs, clomipramine, tramadol, meperidine, levodopa

Increases serotonin levels - serotonin syndrome risk with serotonergic drugs. Methylates levodopa, reducing its effectiveness in Parkinson's disease. AVOID with MAOIs

Timing: Empty stomach. Morning preferred (mildly activating)

Mayo Clinic SAMe guidance; NCCIH SAMe monograph; PMID 20595412 (SAMe + SSRI RCT); Merck Manual SAMe

Tongkat Ali MODERATE

Do NOT combine with:

Diabetes medications (insulin, metformin, sulfonylureas), hormone-sensitive cancer treatments

May lower blood sugar - hypoglycemia risk with diabetes meds. CYP450 enzyme interactions possible. Increases testosterone - contraindicated in hormone-sensitive cancers (prostate, breast)

Timing: With food. Morning preferred

RxList tongkat ali interactions; NCBI LiverTox NBK609015; WebMD tongkat ali

Milk Thistle (Silymarin) LOW

Do NOT combine with:

Warfarin, methadone, statins (atorvastatin), chemotherapy agents

In vitro CYP2C9 and CYP3A4 inhibition, but clinical studies show minimal effect at standard doses. Sensitive drugs (warfarin, opioids, anti-arrhythmics) still warrant caution. Chemotherapy interactions require oncologist supervision

Timing: With food. Typically 200-400mg standardized extract

PMC4164972 (CYP450 clinical study - no significant effect); Pharmacy Times milk thistle interactions; Mayo Clinic milk thistle

Myo-Inositol LOW

Do NOT combine with:

Lithium, diabetes medications (may have additive glucose-lowering effect)

Lithium may interfere with inositol signaling (lithium depletes inositol - this is part of its mechanism). Metformin and myo-inositol may have additive insulin-sensitizing effects - monitor blood glucose

Timing: With food or empty stomach. Typical dose 2-4g/day for PCOS

PMC5655679 (myo-inositol PCOS meta-analysis); MDPI comparative study with metformin

Oregano Oil (Carvacrol) MODERATE

Do NOT combine with:

Anticoagulants, iron/zinc/copper supplements, diabetes medications

Anticoagulant activity from carvacrol/thymol - increased bleeding risk. Reduces absorption of iron, zinc, copper (take 2h apart). May lower blood sugar (hypoglycemia risk with diabetes meds). Case report of hemorrhagic risk (2025)

Timing: With food. Separate from mineral supplements 2h. Stop 2 weeks before surgery

PMID 39793412 (2025 hemorrhagic risk case report); WebMD oregano interactions; StyleCraze oregano oil side effects

Vitamin E MODERATE

Do NOT combine with:

Warfarin, anticoagulants, antiplatelet drugs, chemotherapy

Inhibits vitamin K-dependent clotting factors and platelet aggregation. Risk mainly at >400 IU/day. Standard multivitamin doses (15-30mg) are safe. May interfere with some chemotherapy mechanisms

Timing: With fat-containing food. Standard dose 15mg (22 IU) daily

PMID 8629604 (vitamin E + warfarin); PMC3886776 (vitamin E serum levels and bleeding); Cambridge nutrition reviews molecular basis

Vitamin K2 (MK-7) AVOID

Do NOT combine with:

Warfarin, other vitamin K antagonist anticoagulants

Directly opposes warfarin. Doses as low as 10mcg MK-7 significantly influenced anticoagulation in some individuals. Dose-dependent antagonism of warfarin. DOACs (apixaban, rivaroxaban) are NOT affected because they block different clotting pathways

Timing: With fat. If on warfarin, do NOT take K2 supplements. If on DOACs, discuss with doctor (likely safe)

PMID 23530987 (MK-7 dose-response in anticoagulation); PMC4972987 (K2 and warfarin perioperative); Blood ASH vitamin K supplementation caution

Biotin (Vitamin B7) HIGH

Do NOT combine with:

No direct drug interactions - but causes DANGEROUS lab test interference

FDA warning: high-dose biotin (5000-10000mcg) falsifies thyroid tests, troponin, hormones, and other biotin-streptavidin-based assays. Can mimic Graves disease on labs. One death reported from missed heart attack due to falsely low troponin

Timing: Any time. Stop 48-72h before ANY blood work

PMC5951654 (biotin lab interference); PMC6663274 (thyroid bioassay case series); PMC6802814 (FDA warning case report); AACC guidance document

Choline / Phosphatidylcholine LOW

Do NOT combine with:

Acetylcholinesterase inhibitors (donepezil, rivastigmine), atropine

May increase acetylcholine levels - additive effect with AChE inhibitors. Gut bacteria convert choline to TMA/TMAO (associated with cardiovascular risk at high supplemental doses). Opposes atropine effects

Timing: With food. Dietary choline from eggs is preferred over supplements when possible

NIH ODS choline fact sheet; HelloPharmacist choline interactions; PMC8410632 (choline supplements raise TMAO)

Iodine HIGH

Do NOT combine with:

Thyroid medications (levothyroxine, methimazole), lithium, amiodarone

Excess iodine can cause hyper- OR hypothyroidism depending on underlying thyroid status. Lithium + iodine = additive hypothyroid effect. Amiodarone already contains 37.5% iodine by weight - supplemental iodine is dangerous. Jod-Basedow disease risk in multinodular goiter

Timing: With food. Do not exceed 150-300mcg/day without medical supervision

PMC1070767 (medications affecting thyroid); PMC3028253 (iodine-induced hyperthyroidism); WebMD iodine interactions; Drugs.com iodine + levothyroxine

Riboflavin (Vitamin B2) LOW

Do NOT combine with:

Doxorubicin (chemotherapy), anticholinergic drugs, tetracycline

Minimal drug interactions at standard doses. May affect doxorubicin effectiveness. Anticholinergic drugs may reduce riboflavin absorption. Generally one of the safest supplements

Timing: With food. Typical migraine prevention dose: 400mg/day

Drugs.com riboflavin interactions; NIH ODS riboflavin fact sheet

Thiamine (Vitamin B1) LOW

Do NOT combine with:

No significant drug interactions at supplemental doses

Extremely safe. No known clinically significant drug interactions. Water-soluble - excess is excreted. High-dose IV thiamine can rarely cause anaphylaxis but oral is safe

Timing: With food. Any time of day

Drugs.com thiamine interactions (no significant interactions listed); NIH ODS thiamine fact sheet

Calcium HIGH

Do NOT combine with:

Levothyroxine, antibiotics (tetracyclines, quinolones), bisphosphonates, iron

Chelation reduces absorption of thyroid medication, antibiotics, bisphosphonates, and iron. Separate all by 2-4 hours. Thiazide diuretics + calcium + vitamin D = hypercalcemia risk

Timing: With food (citrate form) or without (carbonate form needs stomach acid). Separate from other meds 2-4h

PMC8002057 (levothyroxine interaction review); Drugs.com calcium interactions

Boron LOW

Do NOT combine with:

Estrogen, hormone replacement therapy

May increase estrogen levels. Generally safe at doses under 20mg/day. Limited drug interaction data

Timing: With food

WebMD boron interactions; NIH ODS boron fact sheet

Chromium MODERATE

Do NOT combine with:

Diabetes medications (insulin, metformin, sulfonylureas), levothyroxine

Additive blood sugar lowering with diabetes meds - hypoglycemia risk. May reduce levothyroxine absorption (take 4h apart). Generally well-tolerated at doses under 1000mcg/day

Timing: With food. Separate from levothyroxine 4h

WebMD chromium interactions; Drugs.com chromium picolinate interactions

D-Ribose LOW

Do NOT combine with:

Diabetes medications (insulin, oral hypoglycemics)

May lower blood sugar - additive hypoglycemia risk with diabetes medications. Limited interaction data

Timing: With meals to reduce GI upset. Typical dose 5g 3x/day

WebMD D-ribose interactions; RxList D-ribose precautions

DAO Enzyme LOW

Do NOT combine with:

No significant drug interactions known

Breaks down dietary histamine in the gut. Does not enter systemic circulation. No known CYP interactions. One of the safest supplements for medication co-administration

Timing: 15 minutes before meals containing histamine

PMID 31807350 (DAO supplementation trial); Drugs.com DAO interactions

Digestive Enzymes LOW

Do NOT combine with:

Blood thinners (bromelain component), acarbose

Bromelain (in some enzyme blends) has mild antiplatelet activity. May reduce effectiveness of acarbose (alpha-glucosidase inhibitor). Otherwise very safe

Timing: With meals

WebMD digestive enzymes interactions; Drugs.com bromelain interactions

Glycine LOW

Do NOT combine with:

Clozapine (antipsychotic)

Extremely safe amino acid. Only known interaction: may affect clozapine levels. No CYP interactions. Used as a sleep aid at 3g before bed

Timing: Before bed for sleep (3g). Any time for other uses

WebMD glycine interactions; Drugs.com glycine interactions

Apigenin (Chamomile) LOW

Do NOT combine with:

CYP1A2 substrates (caffeine, clozapine), CYP3A4 substrates, sedatives

In vitro CYP1A2 and CYP3A4 inhibition. Additive sedation with CNS depressants. Clinical significance at supplement doses is unclear

Timing: Evening preferred (sedating). With food

WebMD chamomile interactions; Examine.com apigenin research

Glutathione (Liposomal) LOW

Do NOT combine with:

Chemotherapy (may reduce effectiveness), nitroglycerin (potentiates vasodilation similar to NAC)

As the body's master antioxidant, may theoretically reduce oxidative-stress-dependent chemotherapy effectiveness. Potentiates nitroglycerin like NAC. Otherwise very safe with minimal drug interactions

Timing: Empty stomach preferred for absorption. Morning or before bed

Drugs.com glutathione interactions; clinical pharmacology references

Ginger (Prokinetic) LOW

Do NOT combine with:

Anticoagulants (warfarin, aspirin), diabetes medications

Mild antiplatelet activity - additive bleeding risk with blood thinners at high doses. May lower blood sugar. Standard culinary doses are safe; supplement doses (500-1000mg) warrant more caution

Timing: With meals or between meals. 500-1000mg extract for prokinetic use

WebMD ginger interactions; Drugs.com ginger interactions

Lavender Oil (Silexan) LOW

Do NOT combine with:

Sedatives, CNS depressants, CYP3A4-metabolized drugs

Additive sedation with benzodiazepines, Z-drugs, alcohol. Silexan (standardized lavender oil) has anxiolytic effects comparable to low-dose lorazepam. Potential CYP3A4 interaction

Timing: With food. Typical dose 80-160mg Silexan daily

Drugs.com lavender interactions; Gaiaherbs lavender safety; Examine.com lavender research

Luteolin LOW

Do NOT combine with:

CYP3A4-metabolized drugs (theoretical), anticoagulants

In vitro CYP inhibition but limited clinical data on drug interactions. Mild antiplatelet properties. Primarily studied for mast cell stabilization in MCAS

Timing: With food. 100-200mg daily

PMID 26190965 (Theoharides mast cell/neuroscience); WebMD luteolin interactions

PEA (Palmitoylethanolamide) LOW

Do NOT combine with:

No significant drug interactions known

Endogenous fatty acid amide - the body already produces PEA. No known CYP interactions. No serotonergic activity. One of the cleanest supplement interaction profiles available

Timing: With or without food. 600mg 2-3x daily for pain

PMID 27220803 (PEA review); Drugs.com PEA interactions

Sulforaphane (Broccoli Sprout Extract) LOW

Do NOT combine with:

CYP1A2 substrates (caffeine, theophylline), thyroid medications (goitrogenic at extreme doses)

Induces Phase 2 detoxification enzymes (NRF2 pathway). May affect CYP1A2 metabolism. Cruciferous compounds are mildly goitrogenic in iodine-deficient individuals - not clinically significant at supplement doses

Timing: With food. Typical dose 30-60mg sulforaphane equivalent

Examine.com sulforaphane research; WebMD broccoli sprout interactions

Chlorella MODERATE

Do NOT combine with:

Warfarin (contains vitamin K), immunosuppressants

Contains vitamin K - may reduce warfarin effectiveness. May stimulate immune function - opposes immunosuppressants. Heavy metal binding properties (used as detox binder)

Timing: With food. Separate from medications 2h (binding properties)

WebMD chlorella interactions; Drugs.com chlorella interactions

Spearmint Tea LOW

Do NOT combine with:

Iron supplements (tanins reduce absorption), diabetes medications

Anti-androgenic properties (used therapeutically in PCOS for hirsutism). Tannins reduce iron absorption. May have mild blood sugar lowering effect. Very safe overall

Timing: Between meals (not with iron-rich foods or iron supplements)

WebMD spearmint interactions; PCOS spearmint tea studies

L-Glutamine LOW

Do NOT combine with:

Lactulose (hepatic encephalopathy), anticonvulsants

Converted to glutamate in the body - may theoretically worsen hepatic encephalopathy (opposes lactulose mechanism). May affect anticonvulsant threshold via glutamate. Otherwise very safe amino acid

Timing: Empty stomach. 5g/day typical dose for gut repair

WebMD L-glutamine interactions; Drugs.com L-glutamine interactions

L-Lysine LOW

Do NOT combine with:

Calcium supplements (increases calcium absorption), aminoglycoside antibiotics

Increases calcium absorption - monitor if already taking high-dose calcium. May increase aminoglycoside toxicity (rare). Otherwise very safe amino acid with minimal interactions

Timing: Empty stomach preferred. 1-3g/day for viral suppression

WebMD lysine interactions; Drugs.com L-lysine interactions

L-Arginine MODERATE

Do NOT combine with:

Blood pressure medications, nitrates (nitroglycerin, sildenafil), anticoagulants

Vasodilator - additive blood pressure lowering with antihypertensives. Potentiates nitrate effects (dangerous hypotension with nitroglycerin or sildenafil). Mild antiplatelet activity

Timing: Between meals. Start at low dose

WebMD L-arginine interactions; Mayo Clinic L-arginine guidance; Drugs.com L-arginine interactions

Stinging Nettle MODERATE

Do NOT combine with:

Blood pressure medications, diabetes medications, anticoagulants, lithium, sedatives

May lower blood pressure and blood sugar. Diuretic effect may affect lithium levels. Mild anticoagulant properties. Additive sedation

Timing: With food. Typical dose 300-600mg extract daily

WebMD stinging nettle interactions; PMID 2189951 (Mittman 1990 allergic rhinitis RCT)

B-Complex LOW

Do NOT combine with:

See individual B vitamins (B1, B2, B6, B12, folate). Biotin component causes lab interference. B6 >100mg/day long-term can cause neuropathy

Standard B-complex doses are very safe. High-dose biotin component can falsify lab tests. High-dose B6 (>100mg/day for months) causes peripheral neuropathy. Methylated forms bypass MTHFR variants

Timing: With food. Morning preferred (B vitamins are mildly energizing)

PMC5951654 (biotin lab interference); NIH ODS B-vitamin fact sheets

MCT Oil / Caprylic Acid LOW

Do NOT combine with:

No significant drug interactions

GI upset (diarrhea, cramping) is the main side effect, especially when starting. No known CYP interactions. Safe with essentially all medications. Start low (1 tsp) and increase gradually

Timing: With food. Start with 1 tsp, increase to 1-2 tbsp over 1-2 weeks

WebMD MCT oil interactions; Drugs.com MCT oil interactions

Japanese Knotweed (Resveratrol) MODERATE

Do NOT combine with:

Anticoagulants, CYP3A4/CYP1A2-metabolized drugs, estrogen

Resveratrol has antiplatelet properties - additive bleeding risk. Inhibits CYP3A4 and CYP1A2 in vitro. Phytoestrogenic - may affect hormone-sensitive conditions. Herxheimer reactions possible at antimicrobial doses (Lyme protocol)

Timing: With food. Start very low for Lyme protocol (Herxheimer risk). Standard resveratrol: 100-500mg daily

PMID 32154254 (Johns Hopkins anti-borrelial study); WebMD resveratrol interactions

Cat's Claw (Uncaria tomentosa) MODERATE

Do NOT combine with:

Anticoagulants, antihypertensives, immunosuppressants, CYP3A4-metabolized drugs

Antiplatelet activity. Lowers blood pressure. Immunostimulant - opposes immunosuppressants. CYP3A4 inhibition. Interacts with anticoagulants and antihypertensives

Timing: With food. Start low (Herxheimer risk in Lyme). Typical dose 500mg 3x/day

PMID 15649507 (anti-borrelial); PMID 32154254 (Johns Hopkins); WebMD cat's claw interactions

Mycotoxin Binders (Charcoal, Bentonite Clay, Cholestyramine) HIGH

Do NOT combine with:

ALL oral medications (binders reduce absorption of everything)

Non-selective binding - activated charcoal and clay bind medications, supplements, and nutrients indiscriminately. MUST separate from all other oral medications by 2-4 hours. Cholestyramine is prescription and has specific interaction warnings

Timing: ALWAYS separate from all medications and supplements by at least 2 hours (4 hours preferred). Take on empty stomach between meals

Drugs.com activated charcoal interactions; FDA cholestyramine label; Clinical toxicology references

PHGG (Partially Hydrolyzed Guar Gum) LOW

Do NOT combine with:

No significant drug interactions known

Soluble prebiotic fiber. May slightly slow absorption of co-administered medications. Does not bind medications like charcoal. Very safe with all drugs

Timing: With water. Can mix into food/drinks. 5g daily for SIBO

PMID 21050236 (Furnari rifaximin + PHGG trial); Drugs.com guar gum interactions

Herbal Antimicrobials (Berberine + Oregano Oil combination) HIGH

Do NOT combine with:

See individual entries for Berberine and Oregano Oil. Combined: additive blood sugar lowering, anticoagulant effects, and CYP interactions

The combination amplifies individual risks. Berberine CYP3A4/2D6 interactions + oregano oil anticoagulant/mineral chelation. Monitor more closely than with either alone

Timing: With meals. Typical SIBO course: 4-6 weeks. Separate from minerals 2h

PMID 14894990 (Chedid herbal vs rifaximin SIBO trial); Combined risk profile from individual entries

Peppermint Oil (Enteric-Coated) LOW

Do NOT combine with:

Cyclosporine (CYP3A4 inhibition), antacids/PPIs (dissolve enteric coating prematurely), iron supplements

CYP3A4 inhibition may increase cyclosporine levels. Antacids/PPIs dissolve enteric coating, causing heartburn and reduced gut-level delivery. May reduce iron absorption. Enteric coating is essential - non-coated causes GERD

Timing: 30-60 min before meals (empty stomach for enteric-coated). Do NOT take with antacids

WebMD peppermint oil interactions; Drugs.com peppermint interactions

Chinese Skullcap (Scutellaria baicalensis) MODERATE

Do NOT combine with:

CYP1A2/CYP2C19 substrates, statins, hepatotoxic drugs, sedatives

Wogonin component inhibits CYP1A2 and CYP2C19. Decreased statin levels in healthy volunteers. Case reports of acute liver injury (hepatotoxicity). Limited safety data - mostly used in Bartonella protocols (Buhner)

Timing: With food. Short courses preferred. Monitor liver function

PMID 33711551 (drug-herb interaction review); PMID 30957370 (liver injury case report); MSKCC scutellaria monograph

Cryptolepis (Cryptolepis sanguinolenta) MODERATE

Do NOT combine with:

Limited data - caution with CYP-metabolized drugs, antidiabetic medications, antimalarials

Very limited published interaction data. Traditional antimalarial - may interact with antimalarial drugs. Contains cryptolepine which has blood sugar lowering effects. Primarily studied for antimicrobial activity against Borrelia and Babesia. NO well-characterized drug interaction profile

Timing: With food. Used in Bartonella/Babesia protocols under practitioner supervision only

Limited published data. Used in Buhner/Zhang Bartonella protocols. No Drugs.com or Examine.com entry exists. Exercise caution

Butyrate (Sodium/Calcium Butyrate) LOW

Do NOT combine with:

May attenuate CYP induction by other drugs (phenobarbital studied). No major known drug interactions

Short-chain fatty acid normally produced by gut bacteria. Supplemental form generally well-tolerated. Animal research shows butyrate may attenuate CYP2H and CYP3A induction - could theoretically affect drug metabolism but clinical significance is unclear. Crosses blood-brain barrier. HDAC inhibitor properties

Timing: With food. Typical dose 300-600mg 2-3x/day. Enteric-coated or tributyrin forms for gut delivery

PMC4903954 (butyrate neuroepigenetics); PMC10359501 (SCFAs gut-brain review); PMID 26614344 (butyrate CYP interaction animal study)

Table 2: Medications That Cause Brain Fog

Important: Do not discontinue medications without medical guidance. Discuss alternatives with your prescriber if you suspect medication-induced brain fog.

Diphenhydramine (Benadryl) HIGH

1st-gen antihistamine

Blocks acetylcholine - high ACB score (3). Crosses blood-brain barrier. Dementia risk with cumulative use

Alternative: Switch to cetirizine/loratadine (2nd-gen, minimal CNS penetration)

AGS 2023 Beers Criteria (PMC12478568); betterhealthwhileaging.net brain-slowing medications

Oxybutynin (Ditropan) AVOID

Anticholinergic

Blocks muscarinic receptors in hippocampus. ACB score 3. Beers Criteria: avoid in older adults

Alternative: Discuss mirabegron (Myrbetriq) - beta-3 agonist, no anticholinergic burden

AGS 2023 Beers Criteria (PMC12478568)

Zolpidem (Ambien) HIGH

Z-drug sleep aid

Same GABA pathways as benzodiazepines. Amnesia, parasomnia, next-day cognitive impairment

Alternative: CBT-I first, then low-dose trazodone or suvorexant

AGS 2023 Beers Criteria; FDA boxed warning for complex sleep behaviors

Metoprolol / Atenolol MODERATE

Beta-blocker (lipophilic)

Lipophilic - crosses BBB readily. Dampens norepinephrine, causes fatigue and cognitive dulling

Alternative: Discuss hydrophilic alternatives (nebivolol, bisoprolol cross BBB less)

EBSCO beta-blocker drug interactions review

SSRIs (class) MODERATE

Antidepressant

Emotional blunting in 40-60% of patients. Paroxetine worst (anticholinergic). Individual variation significant - see specific SSRI entries below

Alternative: Discuss bupropion, vortioxetine (pro-cognitive), or dose reduction

PMC neuropsychiatric review; individual SSRI entries in medication interactions table

Alprazolam / Lorazepam AVOID

Benzodiazepine

Dampens working-to-long-term memory transfer. Dependence develops in 2-4 weeks. Withdrawal can be life-threatening

Alternative: Buspirone (non-addictive), hydroxyzine (short-term), CBT for anxiety

AGS 2023 Beers Criteria; FDA benzodiazepine boxed warning

Gabapentin / Pregabalin MODERATE

Anticonvulsant / nerve pain

Calcium channel modulation, cognitive dulling, dizziness, somnolence. Dose-dependent cognitive effects

Alternative: Discuss dose reduction. Duloxetine or amitriptyline alternatives for neuropathic pain (trade-off: own side effects)

Drugs.com gabapentin interactions; FDA pregabalin label

Omeprazole / Pantoprazole MODERATE

PPI

Long-term B12 and magnesium depletion. Combined PPI + metformin dramatically increases B12 deficiency risk

Alternative: Step down to H2 blockers (famotidine) if possible. Supplement B12 and magnesium with chronic use

PMC3507616 (B12 deficiency with PPI + metformin); PMID Jung 2025 (concomitant use risk)

Amitriptyline / Nortriptyline HIGH

Tricyclic antidepressant

Highly anticholinergic - blocks acetylcholine in hippocampus. Beers Criteria: avoid in older adults. Memory impairment documented after 4 weeks

Alternative: SSRIs (sertraline, escitalopram) or SNRIs with lower anticholinergic burden

AGS 2023 Beers Criteria (PMC12478568); Amitriptyline memory impairment (Springer BF02245119)

Paroxetine (Paxil) HIGH

SSRI (high anticholinergic)

Most anticholinergic SSRI - uniquely problematic for cognition compared to other SSRIs. On Beers Criteria. Also strongest CYP2D6 inhibitor among SSRIs

Alternative: Switch to sertraline or escitalopram (lower anticholinergic burden)

AGS 2023 Beers Criteria (PMC12478568); PharmD Live anticholinergic Beers review

Topiramate (Topamax) HIGH

Anticonvulsant / migraine preventive

Up to 40% experience cognitive deficits. Word-finding difficulty, slowed processing, impaired working memory. Nicknamed 'Dopamax'. Each ug/mL plasma concentration reduces memory accuracy by 3.6%

Alternative: Discuss propranolol, candesartan, or CGRP inhibitors for migraine prevention

PMC4110841 (cognitive impairment evidence review); PMC7572737 (working memory dose-response); Pharmacy Times language impairment

Cyclobenzaprine (Flexeril) HIGH

Muscle relaxant

Structurally identical to tricyclic antidepressants. Strong anticholinergic, antihistamine, and sedative effects. Impairs driving vs placebo in controlled study

Alternative: Methocarbamol (less sedating) or metaxalone (least sedating). Tolperisone showed no cognitive impairment vs placebo

PMID 32390248 (tolperisone vs cyclobenzaprine driving/cognition RCT); StatPearls NBK513362; AAFP muscle relaxant review

Quetiapine (Seroquel) HIGH

Atypical antipsychotic

Strong antihistamine and anticholinergic properties. Somnolence in up to 57%. Worse cognitive performance than risperidone on 9/18 cognitive measures in crossover study

Alternative: Discuss dose reduction, bedtime-only dosing, or alternative if used off-label for sleep

PMID 17854242 (risperidone vs quetiapine cognitive comparison); Drugs.com quetiapine brain fog reports

Opioids (codeine, tramadol, oxycodone, morphine) HIGH

Opioid analgesic

Impairs attention, memory, language, processing speed. 20% higher MCI risk with regular use. Effects worsen >120mg morphine equivalent/day. May persist during pharmacotherapy

Alternative: Non-opioid pain management: NSAIDs, PEA, physical therapy, nerve blocks. Discuss tapering plan

PMC4776316 (prospective cohort - dementia risk); PMC8437064 (opioid cognitive function); Alzheimer's & Dementia Lin 2025 (UK Biobank)

Prednisone / Corticosteroids MODERATE

Glucocorticoid

Declarative memory deficits emerge within 4-5 days. Psychiatric symptoms rare at <40mg/day but 18.4% at >80mg/day. Affects hippocampus and prefrontal cortex. Reversible in most cases

Alternative: Use lowest effective dose. Steroid-sparing agents where possible. Cognitive effects generally reversible within months

PMC181154 (mood and cognitive changes review); Mayo Clinic Proceedings psychiatric adverse effects; Bristol 2023 long-term steroid study

Scopolamine patches AVOID

Anticholinergic

Potent central anticholinergic - causes confusion, memory impairment, and delirium especially in older adults. ACB score 3

Alternative: Ondansetron (Zofran) for nausea. Meclizine for motion sickness (less CNS penetration)

AGS 2023 Beers Criteria (PMC12478568)

Olanzapine (Zyprexa) HIGH

Atypical antipsychotic

High anticholinergic and antihistamine burden. Weight gain compounds metabolic fog. Sedation and cognitive dulling common

Alternative: Discuss aripiprazole (lower metabolic/sedation burden) if appropriate

JAMA Psychiatry CATIE trial neurocognitive effects

Vortioxetine (Trintellix) LOW

Antidepressant (pro-cognitive)

POSITIVE: Only antidepressant with RCT evidence for cognitive improvement independent of mood. Multimodal serotonin modulator

Alternative: This IS the alternative - discuss switching if other antidepressants cause fog

FDA Trintellix label; depression.json cause page references

Bupropion (Wellbutrin) LOW

Antidepressant (pro-cognitive)

POSITIVE: Norepinephrine-dopamine reuptake inhibitor. Less sedation, less sexual dysfunction, less cognitive blunting than SSRIs. Mildly activating

Alternative: This IS the alternative - discuss switching if SSRIs cause fog. Avoid if seizure risk or eating disorder

FDA Wellbutrin label; GoodRx bupropion profile

Table 3: I'm On This Medication - What Supplements Should I Watch?

51 medications with CYP enzyme profiles, supplement interaction details, and cognitive effect ratings. Find your medication below and see which supplements need timing separation, dose adjustment, or avoidance.

Metformin - Biguanide antidiabetic
HIGH

(Glucophage, Glumetza, Fortamet)

CYP Metabolism

Not CYP-metabolized (renal elimination)

Cognitive Effect

neutral

Supplement Interactions

Berberine (additive hypoglycemia, increases metformin levels if taken 2h before), Alpha-Lipoic Acid (additive glucose lowering), Chromium (additive). DEPLETES: B12 (impairs IF-mediated absorption), possibly magnesium

Risk

Hypoglycemia with glucose-lowering supplements. B12 deficiency (57 pmol/L reduction after 4 months). Combined metformin + PPI dramatically increases B12 deficiency risk

What To Do

Monitor B12 annually. Take berberine WITH metformin (not 2h before). Use sublingual B12 to bypass absorption issue

394 drug interactions on Drugs.com (25 major). PMC7308123; PMC5839379; MHRA 2024 B12 monitoring guidance

Verify →
Insulin (all forms) - Hormone
HIGH

(Humalog, Novolog, Lantus, Levemir, Tresiba)

CYP Metabolism

Not CYP-metabolized (degraded by insulin-degrading enzyme)

Cognitive Effect

neutral (treats condition that causes fog)

Supplement Interactions

Berberine (additive hypoglycemia), Alpha-Lipoic Acid (additive glucose lowering), Chromium (additive), Magnesium (may improve insulin sensitivity). All glucose-lowering supplements require dose monitoring

Risk

Hypoglycemia - any supplement that lowers blood sugar adds to insulin's effect. Dose adjustments may be needed

What To Do

Monitor blood glucose more frequently when adding any glucose-lowering supplement. Start supplements at low dose

Drugs.com insulin interaction checker; WebMD berberine interactions

Verify →
Semaglutide - GLP-1 receptor agonist
MODERATE

(Ozempic, Wegovy, Rybelsus)

CYP Metabolism

Not significantly CYP-metabolized (proteolytic degradation)

Cognitive Effect

potentially pro-cognitive (neuroprotective signals in research)

Supplement Interactions

Delays gastric emptying - affects absorption timing of ALL oral supplements. Oral semaglutide (Rybelsus) specifically interacts with levothyroxine absorption

Risk

286 drug interactions (16 major). Main risk is altered absorption timing of oral medications and supplements, not direct pharmacological interaction

What To Do

Take oral supplements 30+ min before or 2h after injection. For Rybelsus: take on empty stomach with <4oz water, wait 30min before other medications

Drugs.com 286 interactions; FDA label 2024; Healthline Ozempic interactions

Verify →
Tirzepatide - GIP/GLP-1 dual agonist
MODERATE

(Mounjaro, Zepbound)

CYP Metabolism

Not significantly CYP-metabolized

Cognitive Effect

potentially pro-cognitive (dual incretin pathway)

Supplement Interactions

Same gastric emptying delay as semaglutide. Affects absorption of oral contraceptives, levothyroxine, and oral supplements

Risk

Altered absorption timing. Less studied than semaglutide for specific supplement interactions

What To Do

Take oral supplements and medications at consistent times. Separate from narrow-therapeutic-index drugs

FDA Mounjaro label; Drugs.com tirzepatide interactions

Verify →
Empagliflozin / Dapagliflozin - SGLT2 inhibitor
MODERATE

(Jardiance / Farxiga)

CYP Metabolism

UGT glucuronidation (not CYP-dependent)

Cognitive Effect

potentially neuroprotective (SGLT2i brain research emerging)

Supplement Interactions

Diuretic supplements (dandelion, hibiscus) increase dehydration risk. Electrolyte supplements may be needed (sodium, potassium loss). Ketogenic diet + SGLT2i = elevated ketoacidosis risk

Risk

Euglycemic diabetic ketoacidosis (rare but serious - 1 in 1,000-10,000). Dehydration and electrolyte imbalance. Risk factors: low carb intake, dehydration, infection

What To Do

Stay well-hydrated. Monitor electrolytes. Avoid very low carb diets without medical supervision. Know signs of ketoacidosis (nausea, vomiting, abdominal pain, fatigue)

PMC4773669; FDA DKA warning; GOV.UK SGLT2i ketoacidosis update

Verify →
Levothyroxine - Thyroid hormone replacement
TREATS FOG HIGH

(Synthroid, Levoxyl, Tirosint, Euthyrox)

CYP Metabolism

Deiodination (not CYP-dependent). Absorption is the critical variable

Cognitive Effect

treats fog (when absorption is adequate)

Supplement Interactions

Calcium (blocks absorption), Iron (blocks absorption), Magnesium (blocks absorption), Zinc (blocks absorption), Coffee (reduces absorption). ALL minerals must be separated 4+ hours. Soy and fiber also reduce absorption. Biotin can falsify thyroid lab results

Risk

Only 31.8% of patients told to separate minerals from levothyroxine by 4h, and only 40.7% of those actually do it. Undertreated hypothyroidism = brain fog

What To Do

Take levothyroxine on empty stomach 60min before breakfast. Separate ALL supplements 4h. Tirosint (gel cap) has fewer absorption interactions. Biotin: stop 48h before thyroid labs

PMC8002057 systematic review; Drugs.com levothyroxine interactions; 2024 Journal of the Endocrine Society

Verify →
Liothyronine - T3 thyroid hormone
TREATS FOG HIGH

(Cytomel)

CYP Metabolism

Deiodination (same as levothyroxine)

Cognitive Effect

treats fog (T3 is the active thyroid hormone)

Supplement Interactions

Same mineral chelation issues as levothyroxine - calcium, iron, magnesium all reduce absorption. Shorter half-life means timing is even more critical

Risk

Narrower therapeutic window than levothyroxine. Mineral interference has proportionally larger impact

What To Do

Same 4-hour separation rule. Take on empty stomach. More sensitive to timing than levothyroxine

Same absorption interaction profile as levothyroxine; FDA Cytomel label

Verify →
Doxycycline - Tetracycline antibiotic
HIGH

(Vibramycin, Doryx, Monodox)

CYP Metabolism

Minimal CYP metabolism (excreted unchanged in urine/feces)

Cognitive Effect

neutral (treats infection that may cause fog)

Supplement Interactions

Calcium (reduces absorption up to 30%), Magnesium (chelation), Iron (chelation), Zinc (chelation), Dairy products (calcium content). ALL minerals form insoluble complexes with doxycycline. Probiotics: separate 2h

Risk

Chelation reduces antibiotic absorption - undertreated infection. Critical for Lyme and Bartonella patients who are also taking mineral supplements

What To Do

Take doxycycline 2h BEFORE or 4-6h AFTER any mineral supplement. Take with water (not milk). Probiotics: 2h separation. Can take with non-dairy food to reduce GI upset

Drugs.com doxycycline interactions; Patient.info calcium interaction guide; PMC9660598 enteral supplement interactions

Verify →
Rifaximin - Gut-specific antibiotic (rifamycin)
TREATS FOG LOW

(Xifaxan)

CYP Metabolism

Minimal systemic absorption (<0.4%). P-glycoprotein substrate

Cognitive Effect

treats fog (SIBO treatment improves cognition)

Supplement Interactions

Cyclosporine (P-gp inhibitor) increases rifaximin blood levels 83-fold. Probiotics: reduced effectiveness if taken simultaneously (separate 2-3h). Warfarin: may alter vitamin K-producing gut bacteria, affecting INR

Risk

Generally very safe due to gut-local action. Main risk is P-gp inhibitor co-administration causing systemic absorption

What To Do

Take probiotics 2-3h after rifaximin. Avoid cyclosporine co-administration. Monitor INR if on warfarin

FDA Xifaxan label 2015; Healthline Xifaxan interactions; DrugBank DB01220; PMC8429411

Verify →
Azithromycin - Macrolide antibiotic
MODERATE

(Zithromax, Z-Pack)

CYP Metabolism

Minimal CYP metabolism (unlike erythromycin, does NOT significantly inhibit CYP3A4)

Cognitive Effect

neutral

Supplement Interactions

Magnesium and aluminum antacids reduce absorption. Probiotics: separate 2h. Less mineral chelation than tetracyclines but still avoid concurrent dosing with minerals

Risk

QT prolongation - avoid combining with supplements that affect heart rhythm. Generally fewer interactions than other macrolides

What To Do

Separate from antacids and mineral supplements by 2h. Take probiotics during and after course (2h separation). Complete full course

Drugs.com azithromycin interactions; FDA label QT warning

Verify →
Metronidazole - Nitroimidazole antibiotic/antiprotozoal
HIGH

(Flagyl)

CYP Metabolism

CYP2A6, CYP2C9 (partial)

Cognitive Effect

neutral (can cause temporary neurological symptoms at high doses)

Supplement Interactions

AVOID alcohol and alcohol-containing supplements (disulfiram-like reaction: nausea, vomiting, flushing). Warfarin (increased anticoagulant effect). Lithium (increased toxicity). Probiotics: take after completing course

Risk

Disulfiram-like reaction with alcohol is severe and well-documented. Avoid alcohol for 48h after last dose

What To Do

Absolutely no alcohol during and 48h after. Separate from warfarin timing. Check all tinctures/extracts for alcohol content

Drugs.com metronidazole interactions; FDA Flagyl label; PMID on disulfiram-like reaction

Verify →
Methotrexate - DMARD / antimetabolite
HIGH

(Trexall, Otrexup, Rasuvo)

CYP Metabolism

Renal elimination (not significantly CYP-metabolized). Displaced by NSAIDs at renal tubule

Cognitive Effect

can cause fog (methotrexate neurotoxicity at high doses)

Supplement Interactions

Folic acid (5mg weekly on different day - reduces toxicity without reducing efficacy). Methylfolate: may reduce methotrexate effectiveness (moderate interaction). NSAIDs: increase methotrexate toxicity by reducing renal clearance. Vitamin C: withhold 48-72h before high-dose MTX

Risk

25 drug interactions on Drugs.com (3 major). Renal toxicity amplified by NSAIDs. Folic acid supplementation is STANDARD of care - not optional

What To Do

Always co-prescribe folic acid 5mg weekly. Avoid NSAIDs. Avoid methylfolate without oncologist/rheumatologist approval. Vitamin C at standard doses (500mg) likely OK; withhold high doses before infusion

PMID 7978695; GoodRx 8 MTX interactions; NHS MTX interaction guidance; Chan 2025 Br J Clin Pharmacol

Verify →
Hydroxychloroquine - DMARD / antimalarial
TREATS FOG MODERATE

(Plaquenil)

CYP Metabolism

CYP2C8, CYP3A4, CYP2D6

Cognitive Effect

treats fog (by controlling autoimmune inflammation)

Supplement Interactions

Antacids (reduce absorption - separate 4h). Avoid immune-stimulating supplements (echinacea, spirulina, alfalfa) in lupus patients. Retinal toxicity risk increases with duration (7.5% at 5+ years, 20% at 20+ years)

Risk

Retinal toxicity is the major long-term risk - irreversible even after stopping. No specific supplement interaction is dangerous, but immune stimulants can trigger lupus flares

What To Do

Annual retinal screening after 5 years. Separate from antacids 4h. Avoid echinacea, spirulina, alfalfa in lupus. Zinc ionophore research is emerging for retinal protection

PMC10267834; AAO retinal toxicity guidelines; Drugs.com HCQ interactions

Verify →
Azathioprine - Immunosuppressant / purine analog
HIGH

(Imuran, Azasan)

CYP Metabolism

TPMT and XO (thiopurine methyltransferase, xanthine oxidase)

Cognitive Effect

can cause fog (bone marrow suppression, fatigue)

Supplement Interactions

AVOID live probiotics (bacteremia risk in immunosuppressed). Allopurinol (MAJOR - inhibits XO, dramatically increases azathioprine toxicity). Warfarin (reduced anticoagulant effect). Immune-stimulating supplements contraindicated

Risk

Live cultures can cause sepsis in immunosuppressed patients. Allopurinol co-administration requires 75% dose reduction of azathioprine

What To Do

No live probiotics. Use heat-killed postbiotics if gut support needed. Avoid echinacea, astragalus, and immune-boosting supplements

PMID 26287986; Drugs.com azathioprine interactions; FDA Imuran label

Verify →
Mycophenolate - Immunosuppressant
HIGH

(CellCept, Myfortic)

CYP Metabolism

UGT glucuronidation (not CYP-dependent)

Cognitive Effect

can cause fog (GI side effects, fatigue)

Supplement Interactions

Iron, calcium, magnesium, aluminum antacids (reduce absorption). AVOID live probiotics (sepsis risk). Cholestyramine (reduces levels). Proton pump inhibitors may reduce absorption of Myfortic

Risk

Mineral chelation similar to levothyroxine. Live organisms dangerous in immunosuppressed patients

What To Do

Separate minerals 2h. No live probiotics. Discuss with transplant team before ANY new supplement

Drugs.com mycophenolate interactions; FDA CellCept label

Verify →
Cyclosporine - Calcineurin inhibitor
AVOID

(Neoral, Sandimmune, Gengraf)

CYP Metabolism

CYP3A4 (major), P-glycoprotein substrate

Cognitive Effect

can cause fog (neurotoxicity at high levels)

Supplement Interactions

St. John's Wort (AVOID - CYP3A4 induction dramatically reduces levels). Quercetin (alters cyclosporine levels unpredictably). Grapefruit (CYP3A4 inhibition increases levels). Curcumin (CYP3A4 interaction). Rifaximin levels increase 83-fold with cyclosporine

Risk

Narrow therapeutic index - small changes in CYP3A4 activity cause transplant rejection (too low) or nephrotoxicity (too high). Most dangerous supplement interaction profile of any immunosuppressant

What To Do

AVOID all CYP3A4-affecting supplements. No St. John's Wort, no quercetin, no grapefruit. Discuss every supplement with transplant team. Drug level monitoring essential

PMC3913293; PMID 21466223 quercetin-cyclosporine; Drugs.com cyclosporine interactions

Verify →
Methylphenidate - CNS stimulant
PRO-COGNITIVE MODERATE

(Ritalin, Concerta, Focalin, Daytrana)

CYP Metabolism

Esterase hydrolysis (NOT CYP-dependent - fewer drug interactions than amphetamines)

Cognitive Effect

pro-cognitive (treats ADHD fog)

Supplement Interactions

Vitamin C / ascorbic acid: acidifies urine, may slightly reduce absorption. Less pH-sensitive than amphetamines. Caffeine: additive stimulation (cardiovascular risk). MAOIs: AVOID (hypertensive crisis)

Risk

Fewer supplement interactions than amphetamines because not CYP-metabolized. Main risks are additive stimulation and MAO-related hypertensive crisis

What To Do

Avoid high-dose vitamin C within 1h of dosing. Moderate caffeine. Never combine with MAOIs or MAOI-active supplements (rhodiola, high-dose St. John's Wort)

FDA Ritalin label; ContemporaryClinics CNS stimulant interactions; Drugs.com methylphenidate interactions

Verify →
Amphetamine / Dextroamphetamine - CNS stimulant
PRO-COGNITIVE HIGH

(Adderall, Vyvanse, Dexedrine)

CYP Metabolism

CYP2D6 (major). Renal elimination pH-dependent

Cognitive Effect

pro-cognitive (treats ADHD fog)

Supplement Interactions

Vitamin C (1000mg+) acts as an OFF switch - acidifies urine, dramatically increases amphetamine excretion. Sodium bicarbonate / alkalizing agents: increase amphetamine levels. Caffeine: additive cardiovascular stimulation. MAOIs: AVOID (hypertensive crisis)

Risk

pH-dependent elimination makes this uniquely sensitive to acid/base supplements. High-dose vitamin C can render medication ineffective

What To Do

Do NOT take vitamin C (1000mg+), citrus juice, or acidifying supplements within 1h before or after dosing. Avoid alkalizing agents. Moderate caffeine. Never combine with MAOIs or rhodiola

FDA Adderall label; Drugs.com vitamin C + Adderall interaction; ADDitude Magazine medication guide; PMID on pH-dependent elimination

Verify →
Atomoxetine - Selective norepinephrine reuptake inhibitor (non-stimulant ADHD)
PRO-COGNITIVE HIGH

(Strattera)

CYP Metabolism

CYP2D6 (major - poor metabolizers have 6-8x higher drug levels)

Cognitive Effect

pro-cognitive (treats ADHD fog)

Supplement Interactions

MAOIs: AVOID (hypertensive crisis - 14-day washout required). Strong CYP2D6 inhibitors increase atomoxetine levels 6-8x: fluoxetine, paroxetine, quinidine. Adjust dose if combining with CYP2D6 inhibitors

Risk

CYP2D6 poor metabolizers (5-10% of population) already have elevated levels. Any supplement inhibiting CYP2D6 can push levels dangerous

What To Do

Avoid supplements with MAO inhibition (rhodiola, high-dose St. John's Wort). If on fluoxetine or paroxetine, atomoxetine dose must be halved. Sertraline is safer to combine

NCBI Bookshelf NBK315951 CYP2D6 genotype; GoodRx top 4 atomoxetine interactions; FDA Strattera label

Verify →
Guanfacine XR - Alpha-2 adrenergic agonist (non-stimulant ADHD)
MODERATE

(Intuniv)

CYP Metabolism

CYP3A4 (major)

Cognitive Effect

can help focus but causes sedation

Supplement Interactions

CYP3A4 inhibitors (curcumin, grapefruit, quercetin) increase guanfacine levels. CYP3A4 inducers (St. John's Wort) decrease levels. CNS depressants (valerian, kava, melatonin) add to sedation

Risk

Sedation and hypotension are primary risks. CYP3A4 interactions can significantly alter blood levels

What To Do

Avoid grapefruit and strong CYP3A4-affecting supplements. Monitor blood pressure. Take at bedtime (sedating)

FDA Intuniv label; Drugs.com guanfacine interactions

Verify →
Modafinil / Armodafinil - Eugeroic (wakefulness-promoting)
PRO-COGNITIVE MODERATE

(Provigil / Nuvigil)

CYP Metabolism

CYP3A4 substrate and moderate inducer. Weak CYP2C19 inhibitor

Cognitive Effect

pro-cognitive (wakefulness, used off-label for MS/chemo fog)

Supplement Interactions

St. John's Wort (CYP3A4 induction - reduces modafinil levels). Caffeine (additive stimulation - anxiety, insomnia, palpitations). Hormonal contraceptives (CYP3A4 induction reduces effectiveness - use backup method). CYP3A4 inhibitors increase modafinil levels

Risk

CYP3A4 induction reduces efficacy of many co-administered drugs. Contraceptive failure is an underappreciated risk

What To Do

Avoid St. John's Wort. Moderate caffeine. Use backup contraception during and 1 month after modafinil. Take morning only (long half-life)

StatPearls NBK531476; PMC5809348 CYP cocktail study; Drugs.com modafinil interactions

Verify →
Sertraline - SSRI
TREATS FOG HIGH

(Zoloft)

CYP Metabolism

CYP2C19 (major), CYP2B6, CYP2D6

Cognitive Effect

treats depression fog but may cause emotional blunting

Supplement Interactions

5-HTP / L-tryptophan (AVOID - serotonin syndrome). St. John's Wort (AVOID - serotonin syndrome, CYP induction). Grapefruit juice (doubles sertraline levels via CYP3A4 inhibition). Rhodiola (MAO inhibition risk). Omega-3 may be synergistic

Risk

Serotonin syndrome is the primary danger. Case reports in elderly patients combining sertraline + St. John's Wort. Grapefruit juice increased plasma levels ~100% in a study of 8 subjects

What To Do

NEVER combine with 5-HTP, St. John's Wort, or rhodiola. Moderate grapefruit. Omega-3 is generally safe to combine. Tryptophan-rich foods (not supplements) are OK

PMC12420457; Drugs.com 5-HTP + Zoloft interaction; PeaceHealth sertraline interactions

Verify →
Escitalopram - SSRI
TREATS FOG MODERATE

(Lexapro)

CYP Metabolism

CYP2C19 (major), CYP3A4

Cognitive Effect

treats depression fog with relatively less blunting than paroxetine

Supplement Interactions

Same serotonergic risks as sertraline: AVOID 5-HTP, St. John's Wort, rhodiola. Lower CYP2D6 inhibition than paroxetine/fluoxetine - fewer supplement interactions overall

Risk

Serotonin syndrome with serotonergic supplements. Otherwise one of the cleanest SSRIs for supplement compatibility

What To Do

Avoid serotonergic supplements. Generally well-tolerated with most other supplements

Drugs.com escitalopram interactions; Lexapro FDA label

Verify →
Fluoxetine - SSRI (strong CYP2D6 inhibitor)
TREATS FOG HIGH

(Prozac)

CYP Metabolism

CYP2D6 (major inhibitor), CYP2C9, CYP2C19. Very long half-life (4-6 days active metabolite)

Cognitive Effect

treats depression fog

Supplement Interactions

AVOID 5-HTP, St. John's Wort, rhodiola (serotonin syndrome). Strong CYP2D6 inhibition increases levels of atomoxetine (6-8x), tamoxifen (reduces efficacy), and many other drugs. Long washout needed (5+ weeks)

Risk

CYP2D6 inhibition is the distinguishing risk - affects more supplements/drugs than other SSRIs. Extremely long half-life means interactions persist weeks after stopping

What To Do

If taking CYP2D6-dependent supplements or drugs, sertraline or escitalopram have less CYP2D6 inhibition

Drugs.com fluoxetine interactions; FDA Prozac label; PMC neuropsychiatric herb-drug interactions

Verify →
Venlafaxine - SNRI
TREATS FOG HIGH

(Effexor, Effexor XR)

CYP Metabolism

CYP2D6 (major), CYP3A4

Cognitive Effect

treats depression/anxiety fog

Supplement Interactions

AVOID 5-HTP (serotonin syndrome risk - Drugs.com rates as 'generally not recommended'). Melatonin (increased drowsiness/confusion). St. John's Wort (AVOID). Black pepper/piperine may inhibit CYP2D6 and increase venlafaxine side effects

Risk

Serotonin syndrome reported even at low doses of venlafaxine. CYP2D6 poor metabolizers at higher risk. Abrupt discontinuation causes severe withdrawal

What To Do

NEVER combine with 5-HTP or St. John's Wort. Melatonin OK at low doses with awareness of added drowsiness. Avoid piperine-containing supplements

Drugs.com 5-HTP + Effexor interaction; PMID 12549949 low-dose serotonin syndrome; DrugBank DB00285

Verify →
Duloxetine - SNRI
TREATS FOG HIGH

(Cymbalta)

CYP Metabolism

CYP1A2 (major), CYP2D6. Moderate CYP2D6 inhibitor

Cognitive Effect

treats depression/pain fog (FDA-approved for fibromyalgia, diabetic neuropathy)

Supplement Interactions

AVOID 5-HTP, St. John's Wort (serotonin syndrome). Fluvoxamine (CYP1A2 inhibition increases duloxetine 460%). Smoking cessation increases duloxetine levels 30%+ within days. Caffeine generally OK (duloxetine does not induce CYP1A2)

Risk

CYP1A2 dependence is unique among antidepressants. Smoking changes and fluvoxamine are the biggest risks. Also a moderate CYP2D6 inhibitor (affects other drugs)

What To Do

If quitting smoking, alert prescriber (dose adjustment needed). Avoid 5-HTP. St. John's Wort contraindicated

PMID 21366359; PMC11616965; FDA Cymbalta label; Drugs.com caffeine + Cymbalta

Verify →
Mirtazapine - Tetracyclic antidepressant (NaSSA)
MODERATE

(Remeron)

CYP Metabolism

CYP1A2, CYP2D6, CYP3A4

Cognitive Effect

can cause fog (sedation, weight gain) but treats insomnia-driven fog

Supplement Interactions

AVOID 5-HTP, St. John's Wort (serotonin syndrome). Additive sedation with valerian, kava, melatonin, L-theanine. Weight gain may be compounded by high-calorie supplements

Risk

Highly sedating - additive CNS depression with sedating supplements is the main risk. Also antihistaminic (weight gain, increased appetite)

What To Do

Take at bedtime. Avoid combining with sedating supplements. Monitor weight

Drugs.com mirtazapine interactions; FDA Remeron label

Verify →
Trazodone - SARI (serotonin antagonist and reuptake inhibitor)
MODERATE

(Desyrel, Oleptro)

CYP Metabolism

CYP3A4 (major)

Cognitive Effect

can cause next-day fog at higher doses

Supplement Interactions

AVOID 5-HTP, St. John's Wort (serotonin syndrome). CYP3A4 inhibitors (grapefruit, curcumin) increase levels. Additive sedation with melatonin, valerian, kava

Risk

Primarily used as sleep aid at low doses. Serotonin syndrome risk with serotonergic supplements. CYP3A4 interactions can increase sedation

What To Do

Low dose (25-50mg) for sleep has fewer interaction risks. Avoid serotonergic supplements. Grapefruit in moderation

Drugs.com trazodone interactions; FDA label

Verify →
Milnacipran - SNRI (FDA-approved for fibromyalgia)
TREATS FOG MODERATE

(Savella)

CYP Metabolism

Minimal CYP metabolism (renal elimination - fewer CYP interactions than other SNRIs)

Cognitive Effect

treats fibromyalgia fog

Supplement Interactions

AVOID 5-HTP, St. John's Wort (serotonin syndrome). MAOIs contraindicated. Fewer CYP-mediated interactions than duloxetine or venlafaxine

Risk

Serotonergic risk same as other SNRIs. Advantage: minimal CYP metabolism means fewer supplement interactions

What To Do

Avoid serotonergic supplements. Generally cleaner interaction profile than other SNRIs

Drugs.com milnacipran interactions; FDA Savella label

Verify →
Propranolol - Non-selective beta-blocker
MODERATE

(Inderal, InnoPran)

CYP Metabolism

CYP1A2 (major), CYP2D6

Cognitive Effect

can cause fog (crosses BBB, dampens norepinephrine - same mechanism as metoprolol)

Supplement Interactions

CoQ10 (may reduce side effects but also adds to hypotension). Melatonin (CYP1A2 overlap - moderate interaction). Magnesium (additive blood pressure lowering). Calcium (may reduce propranolol absorption). Ephedra/ma huang (AVOID - opposing effects)

Risk

Blood pressure lowering supplements add to hypotensive effect. CYP1A2 interactions with fluvoxamine-type supplements. Abrupt discontinuation dangerous (rebound hypertension)

What To Do

CoQ10 supplementation may help with fatigue side effects. Separate calcium 2h. Monitor blood pressure when adding supplements

Drugs.com propranolol interactions; EBSCO beta-blocker drug interactions; Drugs.com CoQ10 + propranolol

Verify →
Fludrocortisone - Mineralocorticoid (POTS/orthostatic hypotension)
TREATS FOG HIGH

(Florinef)

CYP Metabolism

CYP3A4

Cognitive Effect

treats POTS fog (by increasing blood volume)

Supplement Interactions

DEPLETES potassium and magnesium - supplementation typically needed. Licorice root (AVOID - synergistic potassium depletion, severe hypokalemia case reports). Salt/sodium loading (works WITH fludrocortisone - therapeutic). NSAIDs (increase fluid retention risk)

Risk

Hypokalemia is the primary risk. Licorice + fludrocortisone = dangerous synergistic potassium depletion. Potassium supplements are standard co-prescription

What To Do

Always supplement potassium when on fludrocortisone. NEVER take licorice root. Monitor electrolytes regularly. Thermotabs for combined Na/K supplementation

PoTS UK fludrocortisone guide; PMID 33391895 licorice-induced hypokalemia; Standing Up to POTS medication guide

Verify →
Midodrine - Alpha-1 agonist (POTS/orthostatic hypotension)
TREATS FOG MODERATE

(ProAmatine, Orvaten)

CYP Metabolism

Hepatic (prodrug activated by hydrolysis, not CYP-dependent)

Cognitive Effect

treats POTS fog (by increasing peripheral resistance)

Supplement Interactions

Alpha-agonist herbs (ephedra, yohimbe - AVOID, excessive vasoconstriction). Blood pressure-raising supplements add to effect. Fludrocortisone (complementary but monitor for supine hypertension)

Risk

Supine hypertension is the main side effect. Avoid anything that further raises blood pressure. Do not take within 4h of bedtime

What To Do

Avoid ephedra, yohimbe. Monitor supine blood pressure. Elevate head of bed 30 degrees at night

PoTS UK midodrine guide; Drugs.com midodrine interactions; Standing Up to POTS

Verify →
Ivabradine - If channel inhibitor (POTS)
TREATS FOG HIGH

(Corlanor)

CYP Metabolism

CYP3A4 (major)

Cognitive Effect

treats POTS fog (by reducing inappropriate tachycardia)

Supplement Interactions

CYP3A4 inhibitors (grapefruit, curcumin, quercetin) increase ivabradine levels - bradycardia risk. St. John's Wort (CYP3A4 induction - reduces levels). Heart rate-lowering supplements (magnesium high dose) additive

Risk

CYP3A4-dependent metabolism means many supplement interactions. Excessive bradycardia is the primary danger

What To Do

AVOID grapefruit and strong CYP3A4-affecting supplements. Monitor heart rate. No St. John's Wort

FDA Corlanor label; Drugs.com ivabradine interactions

Verify →
Cetirizine - 2nd-gen antihistamine
LOW

(Zyrtec)

CYP Metabolism

Minimal CYP metabolism (renal elimination). Mildly sedating despite being '2nd-gen'

Cognitive Effect

minimal fog (much less than diphenhydramine)

Supplement Interactions

Alcohol (increased sedation). Sedating supplements (valerian, kava, melatonin) add to drowsiness. Not affected by grapefruit. Fewer interactions than 1st-gen antihistamines

Risk

Additive sedation is the main risk. Otherwise very clean interaction profile. Can be mildly sedating in some patients

What To Do

If sedation is a concern, fexofenadine (Allegra) is least sedating. Avoid combining with alcohol or sedating supplements

ScienceDirect 2nd-gen antihistamine review; Drugs.com cetirizine interactions

Verify →
Fexofenadine - 2nd-gen antihistamine (non-sedating)
LOW

(Allegra)

CYP Metabolism

Not CYP-metabolized. OATP1A2 transporter substrate (unique mechanism)

Cognitive Effect

no fog (least sedating antihistamine available)

Supplement Interactions

Fruit juices (grapefruit, orange, apple) REDUCE fexofenadine absorption up to 70% via OATP1A2 inhibition. Take with water only. No significant CYP interactions. No sedation even with alcohol

Risk

Unique juice interaction - opposite of most drugs. Juices REDUCE effectiveness (not increase toxicity). No sedation risk

What To Do

Take with water, not fruit juice. Wait 4h between fexofenadine and juice. Best antihistamine choice for brain fog patients

StatPearls NBK556104; FDA grapefruit interaction notice; Medical Letter fexofenadine and fruit juice

Verify →
Famotidine - H2 receptor antagonist
LOW

(Pepcid)

CYP Metabolism

Minimal CYP metabolism (renal elimination)

Cognitive Effect

minimal fog (used as step-down from PPIs)

Supplement Interactions

Reduces absorption of iron, B12, calcium, magnesium, zinc (by reducing stomach acid). Less severe than PPIs. Does not significantly affect CYP enzymes

Risk

Nutrient depletion with long-term use (same mechanism as PPIs but milder). Monitor B12, iron, magnesium with chronic use

What To Do

Preferred over PPIs for long-term acid suppression. Supplement B12, iron separately (2h apart). Monitor nutrient levels annually

Drugs.com famotidine interactions; Mayo Clinic H2 blocker guidance

Verify →
Cromolyn Sodium - Mast cell stabilizer
TREATS FOG LOW

(Gastrocrom, NasalCrom)

CYP Metabolism

Not significantly metabolized (excreted unchanged)

Cognitive Effect

treats MCAS fog (by stabilizing mast cells)

Supplement Interactions

Virtually no drug-supplement interactions. Works locally in gut (Gastrocrom) or nasal passages (NasalCrom). Does not enter systemic circulation significantly

Risk

One of the safest medications for supplement co-administration. No CYP interactions, no absorption interference

What To Do

Safe with essentially all supplements. May be combined with quercetin and DAO enzyme for MCAS management

Drugs.com cromolyn interactions; FDA Gastrocrom label

Verify →
Nystatin - Polyene antifungal (topical/oral non-absorbed)
TREATS FOG LOW

(Mycostatin, Nilstat)

CYP Metabolism

Not absorbed orally - no systemic metabolism, no liver involvement

Cognitive Effect

treats candida fog (by reducing fungal overgrowth)

Supplement Interactions

Probiotics: take 2h apart (antifungal may reduce probiotic viability in gut). Otherwise virtually no interactions because nystatin is not absorbed

Risk

One of the safest antifungals. No systemic absorption = no systemic interactions. Safe with all supplements except concurrent probiotics

What To Do

Separate probiotics 2h. Otherwise no restrictions. Preferred over fluconazole for safety

NCBI LiverTox NBK548581; Drugs.com nystatin interactions

Verify →
Fluconazole - Triazole antifungal (systemic)
TREATS FOG HIGH

(Diflucan)

CYP Metabolism

Potent CYP2C9 inhibitor, moderate CYP3A4 inhibitor, potent CYP2C19 inhibitor. Inhibition persists 4-5 days after stopping

Cognitive Effect

treats candida fog

Supplement Interactions

Increases levels of ALL CYP2C9/3A4-metabolized supplements and drugs. Warfarin (major - INR increase). Reduces probiotic viability. Berberine, curcumin levels may be affected. Hepatotoxicity risk with concurrent hepatotoxic supplements

Risk

Potent enzyme inhibitor with long-lasting effects. Short courses (1-2 doses) are lower risk than extended treatment. Liver monitoring needed with extended use

What To Do

For short courses (single dose or 3-day), risks are lower. Extended use: monitor liver function, INR if on warfarin. Separate probiotics. Nystatin is safer alternative for mild cases

PMID 25429674; StatPearls NBK537158; Medscape fluconazole interactions

Verify →
Buspirone - Azapirone anxiolytic (non-benzodiazepine)
TREATS FOG MODERATE

(BuSpar)

CYP Metabolism

CYP3A4 (major)

Cognitive Effect

treats anxiety fog without sedation or dependence

Supplement Interactions

Grapefruit juice (CYP3A4 inhibition - increases buspirone levels significantly). St. John's Wort (serotonin syndrome risk - serotonergic properties). 5-HTP (additive serotonergic risk). CYP3A4-affecting supplements alter levels

Risk

CYP3A4-dependent - grapefruit is the most clinically significant interaction. Serotonin syndrome possible but lower risk than with SSRIs

What To Do

Avoid grapefruit. Avoid 5-HTP and St. John's Wort. Otherwise a clean anxiolytic with no dependence risk

Drugs.com buspirone interactions; FDA BuSpar label

Verify →
Hydroxyzine - Antihistamine anxiolytic
CAUSES FOG MODERATE

(Vistaril, Atarax)

CYP Metabolism

CYP2D6, CYP3A4

Cognitive Effect

causes fog (antihistamine sedation, short-term use preferred)

Supplement Interactions

Additive sedation with melatonin, valerian, kava, L-theanine. Anticholinergic properties - may compound with other anticholinergic supplements. Alcohol (additive CNS depression)

Risk

Sedation is the primary interaction risk. Anticholinergic burden in combination with other anticholinergic agents

What To Do

Short-term use only for acute anxiety. Buspirone for chronic anxiety. Avoid combining with sedating supplements

Drugs.com hydroxyzine interactions; FDA label

Verify →
Lamotrigine - Anticonvulsant / mood stabilizer
HIGH

(Lamictal)

CYP Metabolism

UGT glucuronidation (NOT CYP-dependent). Estrogen induces glucuronidation

Cognitive Effect

generally cognitive-neutral (better than valproate/topiramate for cognition)

Supplement Interactions

Oral contraceptives (estrogen reduces lamotrigine levels ~50% - dose adjustment needed). Valproate (inhibits glucuronidation - doubles lamotrigine levels). Folic acid supplementation recommended for women of childbearing age

Risk

Hormonal fluctuations directly affect lamotrigine levels. Starting/stopping oral contraceptives requires dose adjustment. Stevens-Johnson syndrome risk with rapid dose changes

What To Do

Adjust dose when starting/stopping hormonal contraception. Supplement folic acid. Avoid rapid dose changes. One of the most cognitive-friendly mood stabilizers

FDA Lamictal label; Neurology valproate/lamotrigine/OC study; MGH Women's Mental Health lamotrigine-OC FAQ

Verify →
Valproate / Valproic Acid - Anticonvulsant / mood stabilizer
CAUSES FOG HIGH

(Depakote, Depakene)

CYP Metabolism

CYP2C9, CYP2C19, UGT glucuronidation. Inhibits multiple CYP enzymes

Cognitive Effect

causes fog (cognitive dulling, tremor, weight gain common)

Supplement Interactions

Carbapenems (AVOID - dramatically reduce valproate levels). Folic acid (depleted by valproate - supplement recommended). L-carnitine (valproate depletes carnitine, especially in children). Aspirin/NSAIDs (increase free valproate levels). Lamotrigine (doubles lamotrigine levels)

Risk

Teratogenic (pregnancy category X). Hepatotoxic. Depletes folic acid and carnitine. Multiple significant drug interactions

What To Do

Supplement folic acid (especially childbearing age). Consider L-carnitine supplementation. Monitor liver function. Lamotrigine is a less cognitively impairing alternative for bipolar maintenance

GoodRx valproate interactions; FDA Depakote label; Drugs.com valproate interactions

Verify →
Lithium - Mood stabilizer (alkali metal)
AVOID

(Lithobid, Eskalith)

CYP Metabolism

Not metabolized (100% renal elimination). Levels controlled by sodium/water balance

Cognitive Effect

can cause fog (cognitive dulling, tremor, thyroid suppression)

Supplement Interactions

Sodium (decreased intake raises lithium levels; increased intake lowers levels). NSAIDs/ibuprofen (increase lithium 10-400%). ACE inhibitors (increase lithium up to 400%). Diuretics/thiazides (increase lithium 25-400%). Caffeine withdrawal (increases lithium 24%). Potassium-sparing diuretics. Electrolyte supplements ALTER lithium handling

Risk

NARROW therapeutic index - small changes cause toxicity (tremor, confusion, seizures, death). Sodium, NSAIDs, ACE inhibitors, and diuretics are the most dangerous interactions. Caffeine changes also significant

What To Do

NEVER change sodium intake, start NSAIDs, or change diuretics without lithium level monitoring. Avoid ibuprofen (use acetaminophen). Keep caffeine intake CONSISTENT. Monitor lithium levels with any medication or supplement change

PMC7358048; GoodRx 7 lithium interactions; PMID 8521679; PMID 2258452; Medsafe NZ lithium guidance

Verify →
Low-Dose Naltrexone (LDN) - Opioid antagonist (immunomodulator at low dose)
TREATS FOG HIGH

(Compounded (1.5-4.5mg). Full-dose: ReVia, Vivitrol)

CYP Metabolism

CYP3A4 (minor). Mainly hepatic reduction to 6-beta-naltrexol

Cognitive Effect

treats fog (autoimmune/neuroinflammation - used in fibro, MS, long COVID, MCAS)

Supplement Interactions

AVOID all opioid-containing supplements and medications (blocks opioid receptors - precipitates withdrawal). Sedating supplements (valerian, kava, melatonin) may increase drowsiness. Most other supplements are safe. May reduce thyroid medication need as autoimmune activity decreases - monitor TSH

Risk

ABSOLUTE contraindication with any opioid (including tramadol, codeine, opioid cough syrups). At LDN doses (1.5-4.5mg), side effects are generally mild (vivid dreams, transient headache). Therapeutic window is narrow - above 4.5mg loses immunomodulatory benefit

What To Do

Confirm zero opioid use before starting. Start at 1.5mg at bedtime, titrate slowly. Monitor thyroid if Hashimoto's. Take at bedtime (endorphin rebound occurs during sleep)

PMC6313374 (LDN therapeutic review); PMC7528597 (LDN and thyroid hormones); PMID 29885638 (immune-related diseases)

Verify →
Warfarin - Vitamin K antagonist anticoagulant
AVOID

(Coumadin, Jantoven)

CYP Metabolism

CYP2C9 (major), CYP3A4, CYP1A2. NARROW therapeutic index

Cognitive Effect

neutral (prevents stroke - protects cognition indirectly)

Supplement Interactions

Vitamin K (directly opposes warfarin - keep intake consistent, don't eliminate). CoQ10 (structurally similar to vitamin K - case reports of reduced INR). Fish oil >3g/day (additive bleeding). Cranberry juice (CYP2C9 inhibition - case reports including fatality). Curcumin (INR rose >10 in case report). Ginkgo (additive bleeding). St. John's Wort (CYP induction - reduces warfarin levels). Garlic, ginger (mild antiplatelet)

Risk

Most dangerous supplement interaction profile of any common medication. Narrow therapeutic index means small changes cause either clotting (stroke) or bleeding (hemorrhage). EVERY supplement change requires INR monitoring

What To Do

Discuss EVERY new supplement with anticoagulation clinic before starting. Monitor INR within 1 week of any supplement change. Keep vitamin K intake consistent, not zero

Br J Clin Pharmacol Tan 2021 systematic review; PMC3534595 (cardiovascular supplement interactions); UC San Diego warfarin supplement guide

Verify →
Ketamine / Esketamine - NMDA receptor antagonist (dissociative anesthetic/antidepressant)
PRO-COGNITIVE MODERATE

(Spravato (esketamine nasal); IV ketamine (compounded))

CYP Metabolism

CYP2B6 (major), CYP3A4

Cognitive Effect

pro-cognitive (treats treatment-resistant depression; rapid onset)

Supplement Interactions

St. John's Wort (CYP3A4 induction - reduces ketamine levels). Benzodiazepines may diminish antidepressant effect. No clinically significant interactions with standard antidepressants per FDA. CYP3A4 inhibitors (grapefruit, curcumin) may increase ketamine exposure but FDA says dose adjustment not warranted

Risk

Relatively clean interaction profile at clinical doses. Main risks are additive dissociation/sedation with CNS depressants, and blood pressure elevation

What To Do

Avoid St. John's Wort. Benzodiazepines before treatment may reduce efficacy. Most supplements are safe. Administered in clinical setting (Spravato) reduces interaction risk

J Clin Psychiatry ketamine drug interactions review; JNJ SPRAVATO drug interactions; Br J Clin Pharmacol Langmia 2022 pharmacogenetics

Verify →
Spironolactone - Potassium-sparing diuretic / antiandrogen
HIGH

(Aldactone)

CYP Metabolism

Hepatic (thioether formation, not significantly CYP-dependent)

Cognitive Effect

neutral (used for PCOS, acne, heart failure)

Supplement Interactions

Potassium supplements (AVOID - hyperkalemia risk, can cause cardiac arrest). ACE inhibitors + potassium + spironolactone = dangerous combination (K+ rose 1.2 mmol/L in studies). Licorice root (opposes aldosterone blockade). Electrolyte supplements need careful potassium monitoring

Risk

Hyperkalemia is the primary lethal risk. Any additional potassium source (supplements, salt substitutes, electrolyte drinks with potassium) can be dangerous

What To Do

NEVER take potassium supplements without medical supervision. Monitor electrolytes regularly. Avoid potassium-containing salt substitutes. Check electrolyte drink labels for potassium content

PMC4955086 (electrolyte disturbance with diuretics/ACEi); Drugs.com spironolactone interactions

Verify →
Amoxicillin - Penicillin antibiotic
LOW

(Amoxil, Augmentin (with clavulanate))

CYP Metabolism

Minimal CYP metabolism (renal elimination)

Cognitive Effect

neutral (treats infection)

Supplement Interactions

Probiotics (separate 2h - antibiotic kills probiotic organisms). Oral contraceptives (possible reduced effectiveness - use backup). Fewer mineral chelation issues than tetracyclines. Methotrexate (reduced renal clearance - increased toxicity)

Risk

Generally one of the safest antibiotics for supplement co-administration. Main consideration is probiotic timing and completing the full course

What To Do

Take probiotics 2h after amoxicillin. Continue probiotics for 2 weeks after finishing course. Can take with food to reduce GI upset

Drugs.com amoxicillin interactions; FDA label

Verify →
Tizanidine - Alpha-2 adrenergic agonist (muscle relaxant)
CAUSES FOG HIGH

(Zanaflex)

CYP Metabolism

CYP1A2 (major - critical interaction pathway)

Cognitive Effect

causes fog (sedation, muscle relaxation)

Supplement Interactions

CYP1A2 inhibitors dramatically increase tizanidine levels (fluvoxamine increases AUC 33-fold). Caffeine withdrawal may increase levels. Additive sedation with melatonin, valerian, kava. Additive blood pressure lowering with magnesium, L-theanine

Risk

CYP1A2-dependent metabolism makes this extremely sensitive to enzyme inhibitors. Excessive sedation and hypotension are the main dangers

What To Do

Avoid CYP1A2-inhibiting supplements. Keep caffeine intake consistent. Take at bedtime when possible. Baclofen is an alternative with different metabolism

FDA Zanaflex label (CYP1A2 interaction warning); Drugs.com tizanidine interactions

Verify →
Montelukast - Leukotriene receptor antagonist
LOW

(Singulair)

CYP Metabolism

CYP2C8, CYP3A4

Cognitive Effect

can cause fog (FDA boxed warning: neuropsychiatric events including confusion, depression, suicidal ideation)

Supplement Interactions

Few significant supplement interactions. St. John's Wort (CYP3A4 induction may reduce levels). Generally safe with most supplements

Risk

FDA boxed warning for neuropsychiatric events (depression, suicidal thoughts, agitation) - not a supplement interaction but important context for brain fog patients

What To Do

Monitor mood closely. Report any neuropsychiatric symptoms immediately. Intranasal steroids are alternatives for allergic rhinitis

FDA Singulair boxed warning (March 2020); Drugs.com montelukast interactions

Verify →

A Note on Statins

Recent large-scale evidence has shifted the consensus - statins are now considered potentially neuroprotective. They should not be discontinued for cognitive concerns without discussing with your prescriber.

Frequently Asked Questions

Which supplements are dangerous with SSRIs?

5-HTP, St. John's Wort, and rhodiola should be avoided with any SSRI due to serotonin syndrome risk. Serotonin syndrome is rare but serious and can be life-threatening. Omega-3, magnesium, and vitamin D are generally safe with SSRIs. Always verify with your pharmacist before adding any supplement to an SSRI.

Can I take supplements with blood thinners like warfarin?

Warfarin has the most dangerous supplement interaction profile of any common medication. Vitamin K directly opposes it, CoQ10 may reduce its effect, and supplements like ginkgo, curcumin, fish oil (>3g/day), and cranberry juice can increase bleeding risk. Keep vitamin K intake consistent (don't eliminate it) and check INR within 1 week of any supplement change.

Does metformin deplete vitamin B12?

Yes. Metformin impairs B12 absorption through the intrinsic factor pathway. A meta-analysis found B12 levels reduced by an average of 57 pmol/L after 4 months. The MHRA recommends monitoring B12 in all metformin patients. Combined metformin + PPI use dramatically increases deficiency risk. Use sublingual methylcobalamin to bypass the absorption issue.

What medications cause brain fog as a side effect?

The most common fog-causing medications include anticholinergics (diphenhydramine, oxybutynin, amitriptyline), benzodiazepines (alprazolam, lorazepam), Z-drugs (zolpidem), topiramate ("Dopamax"), opioids, gabapentin/pregabalin, PPIs (via B12 depletion), and lipophilic beta-blockers (metoprolol). Alternatives exist for most - discuss with your prescriber. Do not stop medications without medical guidance.

Are there any pro-cognitive medications?

Vortioxetine (Trintellix) is the only antidepressant with RCT evidence for cognitive improvement independent of mood. Bupropion (Wellbutrin) causes less cognitive blunting than SSRIs due to its norepinephrine-dopamine mechanism. Modafinil promotes wakefulness and is used off-label for MS and chemo fog. These are prescription medications - discuss with your doctor if your current medication is causing fog.

Supplement Timing Chart → How to Talk to Your Doctor →

Source: whatisbrainfog.com/drug-interactions/ - Not medical advice. Verify with your pharmacist.

Not medical advice. Consult your pharmacist and physician.

Related Causes

Drug interaction pages should route to medication and psych overlap causes.

MedicationsAnxietyDepressionSleep IssuesCortisol/Stress