Professional Documents
Culture Documents
Drug-Supplement, Drug-Nutrient
Leo Galland, M.D.
Applied Nutrition, Inc.
www.nutritionworkshop.com
Overview
Of almost 900 drugs and fixed-drug
combinations used in the U.S.:
Almost 400 may deplete specific nutrients.
Over 400 may interact with food or food
components.
Over 300 have been shown to interact with
dietary supplements, with adverse and
beneficial interactions equally common.
Types of Interactions
Pharmacodynamic: two substances exhibit
pharmacologic actions that reinforce or
interfere with each others actions.
Pharmacokinetic: the absorption,
distribution, excretion or enzymatic
transformation of one substance is altered
by another. Most adverse interactions are of
this type.
Pharmacokinetic Mechanisms
Alteration of gastrointestinal or urinary pH.
Stimulation, induction or inhibition of
enzymes involved in biotransformation or
transport of drugs or nutrients .
Displacement of a drug from binding to
plasma proteins.
Alteration of solubility.
Effects of Interactions
Nutrient depletion: Individual nutrients may have
their dietary requirement increased by specific
drugs (or supplements).
Adverse: A specific supplement may undesirably
decrease or increase the effect of a drug or
supplement being taken.
Beneficial: Drugs (or supplements) may have their
actions enhanced or side effects diminished by
specific supplements.
Phenytoin-induced Depletions
Phenytoin may deplete biotin, folate,
thiamine, vitamin D (causing hypocalcemia
and osteomalacia and vitamin K.
Memory impairment is associated with
reduced RBC folate. Folic acid, 1 mg/day,
prevents deficiency without adversely
affecting phenytoin metabolism.
CYP1A2
Liver only. Inactivates caffeine and
bioactivates aromatic and heterocyclic
amines; large inter-individual differences
(up to 100-fold). Induced by char-broiled
meat, cigarettes, pollutants, dioxins and
cruciferous vegetables.
CYP3A4
Liver and small intestine.
Transforms about 50% of common drugs.
Induced by St. Johns wort (liver, intestine)
and Echinacea (liver only).
Inhibited by peppermint oil and piperine.
Intestinal but not liver CYP3A4 is inhibited
by grapefruit juice, Seville orange juice and
Echinacea.
Adverse Pharmacodynamic
Interactions
Antithrombotic Interactions
35 natural products inhibit platelet function
in vivo following oral use. They may
reinforce each other or interact with
antithrombotic medication.
Aspirin-vitamin E interaction: aspirin
inhibits platelet aggregation; vitamin E
inhibits platelet adhesion to endothelium.
Aspirin-Vitamin E Interactions
a-Tocopherol (50 IU/day) raised risk of gingival
bleeding 25% among ASA users.
400 IU/day a-tocopherol added to 325 mg ASA/day
reduced incidence of TIAs compared to aspirin
alone.
Vit E 50 IU/day, decreased ischemic stroke by 30%
but increased hemorrhagic stroke by 145% in
hypertensive, non-diabetic male smokers. In
diabetics, there was no increase in hemorrhagic
stroke and ischemic stroke decreased by 70%.
Warfarin Interactions
49 natural products may interfere with
warfarin; 21 confirmed, 28 possible.
Herbal coumarins might compete for
binding to plasma protein, increasing
plasma free warfarin concentration.
Controlled studies found no effect on
vitamin E or coenzyme Q10 on INR of
patients taking warfarin.
Beneficial Drug-Supplement
Interactions
Reflect additive/complementary effects of
supplements and drugs, or amelioration of
toxic drug effects by supplements.
Fish oils enhance anti-inflammatory,
antiarrhythmic, anti-lipemic, antidepressant,
and neuroleptic drugs, beta-blockers,
lithium and insulin. EPA and DHA may
have differential effects.
Acetaminophen Toxicity
Protective supplements:
N-acetyl cysteine (clinical use)
L-methionine and SAMe
Milk thistle
Andrographis
Schisandra
ASA/NSAID Gastropathy
Protective supplements (human trials):
Vit C (500-1000 mg bid)
SAMe 500 mg/day
Cayenne 20 grams
Deglycyrrhizinated licorice 350 mg tid
Colostrum 125 mg tid
Cisplatin Toxicity
Protective supplements:
Bismuth 150 mg/kg/day X 10days
Ginkgo bilomba 100 mg/kg single dose
Glutathione 5 gm i.v.
MgSO4 3 gm i.v./ Mg 160 mg tid
Silibinin 200 mg/kg i.v. single dose
N-acetyl cysteine 8 gm/day
Selenium 4000 mcg/day X 8 days
Vitamin C 50-200 mg/kg i.v. single dose
Vitamin E 300 IU/day till 3 months post-chemotherapy
Conclusion
Almost half the drugs commonly used in the
US may deplete specific nutrients, creating a
need for nutritional supplementation.
Adverse interactions have received extensive
press coverage.
Beneficial drug-supplement interactions are
at least as important and permit creative
nutritional therapies.