Medications,

Herbal
Supplements, & Diet-Drug
Interactions

Medications in Disease Treatment

• Medications used to prevent & treat health problems
• Herbal supplements often used as alternative therapy
• Any ingested chemical can affect metabolism & produce adverse
effects
• Drug-drug interactions
• Diet-drug interactions
Medications in Disease Treatment (con’t)
Prescription drugs
• Use requires physician evaluation of patient’s condition
• Given to treat serious conditions • Although OTC drugs are considered safe enough
for self-medication, they can cause adverse effects
• May cause severe side effects when used inappropriately
Over-the-counter drugs
• Can be used safely & effectively without medical supervision
• Used for less serious conditions
• May cause adverse effects, especially if used
inappropriately
Generic drugs
• Chemically identical & act the same as original drug
• Cost significantly less than brand-name counterparts

Medications in Disease Treatment (con’t)

• Risks from medications
• Any drug carries some risk of adverse Potential Risks
reaction • Side effects
• Drug considered “safe” when benefits of
use outweigh potential risks • Drug-drug interactions
• Risks greater when incorrectly used • Diet-drug interactions
(prescribed &/or administered)
• Medication errors-see Table 15-1,
Inappropriate Abbrev., p.440
Medications in Disease Treatment (con’t)
• Elderly people using multiple meds are especially • Patients at greatest risk
susceptible to adverse effects • Pregnant & lactating women
• Children
• Older adults
• Individuals with medical
conditions that were not studied
during drug development
• Health professionals should
discuss risks & benefits of
medications; alert patients to
potential dangers & solutions

Medications in Disease Treatment (con’t)

• Reducing risk
• Patient counseling & education
• Discussion of lifestyle or dietary practices as alternatives to
drug therapy
• Assessment of all medications, including prescription, OTC
& dietary supplements
• Monitoring side effects
• Assessment of patient understanding of medication use,
interactions & drug safety

Nutrition & Diet Therapy (7th Edition)

 Herbal Supplements
• Widely used by consumers to improve general • Manufacturers & distributors are responsible
health & prevent or treat specific illnesses for determining safety
• Do not require FDA approval before marketing • Not required to provide evidence
• FDA must show that herbal supplement is • FDA notification of illness or injury related to
unsafe before it can be removed from use of product is not required
marketplace (ex. ephedrine)

Effectiveness & Safety

• Benefits of use of herbal products is unclear
• Many herbal “remedies” of dubious effectiveness
• Efficacy: limited number of studies to support traditional uses & benefits
• Consistency in ingredients: variations occur in composition of herb & in preparation; may contain
harmful components
• Safety issues: products often considered “natural,” therefore safe; may have toxic effects,
however—some serious, even dangerous
• Interactions: may potentiate or interfere with actions of other herbs or drugs
• Contamination: some products found to contain lead & other toxic metals; other contaminants
include molds, bacteria, pesticides
• Adulteration of imported products, including addition of synthetic drugs not identified on labels
Use of Herbal Products in Illness
• Self-medication & herbal remedies may delay appropriate treatment
& allow progression of illness
• Herbal products may interact with other medications—lack of
research makes assessment of interactions difficult
• Herbal products are not reliable treatment for medical conditions

Nutrition & Diet Therapy (7th Edition)

Nutrition & Diet Therapy (7th Edition)

© World Health Organization 2021

The use of herbal medicines is high, increasing, and predominant

in certain types of patient, culture and disease states.
1. Culture factors:
• A 2014 study estimated that 18.8% of respondents were using at least one
“plant-based supplement” in Europe (Garcia-Alvarez et al., 2014).
• In South Africa, over 27 million people have been reported to use herbal
medicines and there are an estimated 200 000 traditional healers (Abdullahi,
2011). Up to 60% of South Africans consult these healers, usually in addition
to using modern biomedical services (Van Wyk et al., 2009).
• In Japan, according to a survey in 2011, 89% of doctors prescribe Kampo
products(traditional herbal medicine) in their daily practice (Arai and
Kawahara, 2019).
• Popular use of herbal medicines in Brazil is often due to poor medical and
pharmaceutical assistance and the high cost of treatment with conventional
medicines (Mazzari and Prieto, 2014).
The use of herbal medicines is high, increasing, and predominant
in certain types of patient, culture and disease states.

2. dramatic global rise in herbal medicine use and sales

The expanding commercial market over the past 50 years:
• Sales of herbal dietary supplements in the United States of America surpassed
US$ 8.8 billion in 2017(Smith et al., 2019).
• In China, the herbal medicines market was worth US$ 100–120 billion in the
period 2014–2016, representing about 30% of the pharmaceutical industry
(Dang et al., 2016).
• Sales of herbal medicines in Brazil in 2014 reached US$ 343.7 million
(Carvalho et al., 2018).
• In South Africa, the herbal product trade has been estimated to contribute
over US$ 200 million to the economy.

The use of herbal medicines is high, increasing, and predominant

in certain types of patient, culture and disease states.

3. parallel increase in the number of people taking conventional

medicines and traditional or complementary medicinal products
concurrently.
• The increasing consumption and concomitant expansion of the herbal
products market have raised concern among healthcare professionals,
researchers, regulatory authorities and consumers regarding herb–
drug interactions (HDIs).
• The practice of using combinations of herbal medicines and
conventional medicines, whether prescribed or bought over-the-
counter, to improve therapeutic benefits.
• According to a British study, the prevalence of taking herbs or dietary
supplements concurrently with prescription medicines in elderly people was
33.6% (Agbabiaka et al., 2017).
• People frequently fail to tell their doctors, and doctors often fail to
ask their patients, about use of herbal medicines.

Beneficial and harmful

interactions
 Beneficial interactions
Herb–drug interactions Herb–herb interactions
The use of herbal formulae and their positive effects on • The therapeutic efficacy of certain herbal medicines can
people. be augmented by the administration of other herbs
Examples: through synergistic, additive, chemical or metabolic
• Herbal formulas for receiving chemotherapy was reviewed mechanisms, including increasing biological effects
through more than one mechanism or altering absorption
by Qi et al. (2015). and bioavailability.
• E.g: A sustained improvement of test responses following treatment
• In Japan, many doctors prescribe Kampo medicines to with the ginkgo–ginseng combination was observed compared with
manage cancer-related symptoms and outcomes (Amitani use of the individual herbs (Scholey and Kennedy, 2002), although no
mechanism for this synergistic effect was postulated.
et al., 2015).
• Alternatively, a herbal medicine may reduce the toxicity
• Chinese herbal medicines have been used successfully in of another herb, for example by reducing the
the treatment of various diseases, including drug-resistant bioavailability of a specific component.
enterobacteria infection (Cai et al., 2017).

• Schisandra sphenanthera Rehder & E.H. Wilson is used in

traditional Chinese medicine as a hepatoprotective agent
in people undergoing liver transplant who are also being
treated with the immunosuppressant tacrolimus.

Harmful interactions
Herb–drug interactions Herb–herb interactions
• The overall clinical effects of herbal combinations are
St John’s wort (Hypericum perforatum L.) was one of the first expected and intended to be the result of complex
herbs to be implicated in case reports of drug interactions, interactions between components of the mixture.
and it remains the most commonly cited.
The concomitant use of St John’s wort with the anticoagulant • Bioavailability enhancers may enhance the effects of
warfarin, immunosuppressants (e.g. ciclosporin), other toxic compounds taken at the same time, whether
in the same herbal medicine or in a different product, and
antiretrovirals (e.g. indinavir, nevirapine), inotropics (e.g.
may need to be considered
digoxin) or antineoplastics (e.g. imatinib, irinotecan) may
result in reduced plasma concentrations and reduced • To avoid harmful interactions, multi-herb and fixed
efficacy of these medicines (Russo et al., 2014). formulae are usually produced according to strict rules
governing appropriate combinations based on traditional
properties .
Other herbs have since been reported to be involved in HDIs,
• In traditional Chinese medicine, specific combinations of herbs have
but the evidence for many is inconclusive. been claimed to be detrimental when taken together; these are
Check the next slide! described as the “18 incompatible medicaments”, reported to cause
adverse reactions when used in combination (see Table 2).
Dietary Supplements & amp; Herbal Medications,
©2022 McGraw Hill
The American Academy of Family Physician,
2017
The American Academy of Family Physician,
2017

Class activity
Supplements and ulcerative colitis (UC)
• X is 33 years old suffered from uncontrolled UC although he was
committed to medical and biological treatments.
• He was “googling” his condition all over the internet and social media
platforms.
• Until he read about a certain hospital in MENA region that sells “UC
herbal package”

Screenshots from the website

The package includes 17 different type of herbs!

How much do you think this
package costs?
Who do you think will buy it?

•Who do you think

will buy it?
 Discussion

• This is your client …

• what’s your job as a
dietitian ?

Vitamin\mineral- drug interaction

Several important factors before intake:
• When managing interactions between medications and vitamin/mineral
supplements, the pharmacist needs to consider:
1. to determine the need for the supplement during the time the medication is to
be taken. For a short course of medication, it is usually possible to discontinue
the supplement until the therapy is completed.
2. To identify alternatives. For example, if the interacting substance comes from
an antacid that the patient needs to treat symptoms of gastroesophageal reflux
disease, an alternative such as an H2-blocker or proton pump inhibitor can be
used during the course of the medication.
3. If the affected medication is to be taken chronically, and the supplement is
deemed necessary, the pharmacist should work with the patient and the
prescriber to suggest alternatives that would limit exposure to potentially
dangerous drug interactions.

Vitamins and Drug Interactions

• Vitamin A
• fat-soluble vitamin found in everyday foods, including liver, yellow-orange fruits and
vegetables such as carrots, margarine, milk, and dark green, leafy vegetables such as
spinach.
• It is not commonly available as a supplement on its own; however, it can be found as a
component of multivitamins and combination supplements targeted towards improving
skin, hair, and nails.
• Vitamin A plays an important role in vision, bone growth, cell differentiation, and the
immune system.
• Vitamin A deficiency often leads to problems with eyesight, a situation less common in
the United States than in underdeveloped countries where nutrition may be poor.
• Some conditions such as celiac disease, Crohn's disease, and pancreatic disorders may
lead to malabsorption of vitamin A from the diet.
 Vitamins and Drug Interactions
• Vitamin A (cont’d)
Interactions with vitamin A become a concern with the use of products
classified as retinoids- -compounds that are chemically similar to vitamin A.
• Retinoids such as isotretinoin (Accutane) and acitretin (Soriatane) are
indicated for the treatment of acne and psoriasis, respectively.
• When retinoid products are prescribed, there is concern of vitamin A
toxicity.
• Pharmacists should alert patients who are taking retinoid products to the
importance of avoiding excess vitamin A. They should also educate patients
about the signs and symptoms of vitamin A toxicity, such as nausea,
vomiting, dizziness, blurred vision, and poor muscle coordination.

Vitamin B6 (Pyridoxine)
A water-soluble vitamin used to treat deficiencies in vitamin B6 and some types of anemia. Foods rich in pyridoxine
include meats, whole grains, and certain fruits and vegetables.
Pyridoxine has been shown to decrease the effects of both phenytoin (dilantin – anti-seizure) and levodopa (CNS agent –
Parkinsons) .
1. Phenytoin
There is limited evidence that high doses of pyridoxine reduce phenytoin serum concentrations, thereby reducing the
efficacy of phenytoin.
One study of patients with seizure disorders found an association between pyridoxine 200 mg/day and reductions in
phenytoin concentration of nearly 50%. Effects of pyridoxine doses lower than 200 mg/day on phenytoin serum
concentration have not been established; however, lower doses can be considered if someone taking a multivitamin
presents with low phenytoin serum concentrations. In these instances, it may be necessary to discontinue or lower the
dosage of the multivitamin or to increase the dosage of phenytoin
2. Levodopa
This effect is not seen when levodopa is prescribed in combination with carbidopa, which prevents the interaction from
occurring. In the rare instance that patients are taking levodopa in absence of carbidopa, pharmacists should advise their
patients to avoid any products containing pyridoxine, because even smaller doses, such as 10 to 25 mg of pyridoxine, may
be enough to inhibit levodopa.
• Pharmacists should strongly encourage the switch to a levodopa/carbidopa combination product if a patient is not already taking this
combination therapy.
 Vitamin E:
• Vitamin E is a fat-soluble vitamin that is used in an array of ailments,
including vitamin E deficiency, atherosclerosis, Alzheimer's disease, and
various cancers. It is also a common supplement taken by patients with
cardiovascular disease.
• Case reports have documented an increased risk of bleeding in patients
taking vitamin E and warfarin concomitantly. This adverse effect is more
likely to occur with larger doses of vitamin E (>800 IU) rather than
smaller doses found in multivitamins.
• Therefore, pharmacists should advise patients taking warfarin to take a
multivitamin for their daily source of vitamin E rather than a supplement
containing only vitamin E.

Vitamin E & Chemotherapy:

• There is controversy over vitamin E and other antioxidants with respect
to chemotherapy. A theoretical interaction has been proposed whereby
antioxidants interfere with the oxidative mechanism of the
chemotherapeutic agent, thereby reducing its effectiveness.
• The clinical implications of this interaction is still unknown; but it might
be worthwhile, until more is known, to counsel patients about avoiding
antioxidant supplements while undergoing chemotherapy treatments
that rely on this mechanism.
• It is important to note that antioxidants are sometimes used to prevent
or lessen the toxic effects of specific agents. Patients on chemotherapy
should be counseled not to supplement on their own and to inform
their oncologist of all dietary supplements and alternative therapies.
Vitamin K
• Vitamin K is indicated to reverse supratherapeutic international normalized ratio
(INR) caused by warfarin. When warfarin and vitamin K–containing products are
taken together, the activity of warfarin is decreased and results in a decreased
prothrombin time and INR.
• This puts the patient at risk for suboptimal anticoagulation, possibly leading to
thromboembolic events such as deep venous thrombosis, pulmonary embolism,
myocardial infarction, or stroke.
• Vitamin K is obtained from the diet through green, leafy vegetables such as
spinach and broccoli.
• Pharmacists should advise all patients taking warfarin to eat consistent diets of
green, leafy vegetables and avoid inconsistent use of supplements that contain
vitamin K (i.e., patients should not routinely change their intake of vitamin K–
containing supplements).

Niacin
• Niacin is a B-complex vitamin used for the treatment of hyperlipidemia and
pellagra.
• Patients may try to self-treat high cholesterol with a niacin supplement.
• The combination of niacin and HMG-CoA reductase inhibitors (statins) may
increase the risk of myopathies or rhabdomyolysis.
• Pharmacists are likely to encounter this interaction, since statins are among the
most commonly prescribed medications. The use of niacin with statins should be
recommended only if the benefits of lipid-lowering outweigh the risks of
myopathies and rhabdomyolysis. Typically, the interaction occurs at doses of 1
g/day or greater of niacin. Generally, over-the-counter niacin supplements are
not supplied in doses this high. Pharmacists should encourage patients to take
niacin supplements only under the supervision of a physician.
 Folic acid
• Folic acid is a B-complex vitamin used to treat and prevent folic acid deficiency.
• Folic acid supplementation is commonly recommended during methotrexate therapy as
prophylaxis against toxicities in patients with rheumatoid arthritis and psoriasis.
• Folic acid deficiency is common in these patients, since methotrexate inhibits dihydrofolate
reductase (an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid). Once metabolized to
tetrahydrofolate, folic acid aids in multiple biochemical processes to synthesize DNA, RNA, and
various proteins.
• Studies have shown that folic acid supplementation reduces toxicities of methotrexate without
affecting efficacy in long-term, low-dose methotrexate therapy for rheumatoid arthritis or
psoriasis.
• Pharmacists should recommend folic acid supplementation in patients prescribed methotrexate
for rheumatoid arthritis or psoriasis, especially if adverse effects or toxicities, such as
abnormalities in blood cell counts and varying degrees of mucositis and diarrhea, are present.
However, it is important to note that some evidence suggests that folic acid reduces the efficacy of
methotrexate in cancer therapy.
Folic acid has also been reported to decrease the efficacy of phenytoin, but only at doses 5 mg/day
or greater, which would be an unlikely dose for supplementation with over-the-counter products.

Minerals and Drug Interactions

Calcium
• Calcium is a mineral supplement taken primarily to prevent or treat osteoporosis.
• It is found in dairy products and is available as a supplement or as a component of some antacids, such as Tums.
• One study determined that 67% of women and 25% of men take a calcium supplement regularly; because calcium is associated
with significant drug interactions, pharmacists should question their patients about calcium intake.
Calcium interacts with prescription medications by limiting their absorption through chelation.
• Significant interactions have been observed between calcium and certain antibiotics--namely tetracyclines and fluoroquinolones.
• Calcium carbonate can reduce the bioavailability of ciprofloxacin by 40%, which could result in inadequate infection treatment and increased
complications.
• Patients taking tetracyclines or fluoroquinolones should avoid the supplement altogether during the course of therapy, which is usually a short
period of time.
• Typically, pharmacists will instruct patients to space the doses of medications and/or supplements whose absorption is affected by
binding. Controversy, however, exists on how much time is long enough to wait between doses. A minimum of two hours is usually
mandated, with some sources citing four to six hours as a minimum recommendation. For example, it is recommended that doses
of calcium and levothyroxine be separated by at least four hours, because the former decreases the bioavailability of the latter.

Calcium
• In addition, it is important to note that several medications, when used
chronically, can affect the body's utilization of calcium.
• Corticosteroids decrease the absorption of calcium, which, over time, can lead to
osteoporosis.
• Loop diuretics increase the excretion of calcium, while drugs that affect vitamin D
(which promotes of calcium absorption), such as phenytoin, phenobarbital, and
orlistat, may decrease the amount of calcium absorbed from the diet.
• Patients taking these medications could benefit from a calcium supplement,
especially one containing vitamin D.
• Pharmacists are in a key position to speak with patients taking these medications
and to recommend adequate calcium intake and supplementation, particularly
for patients with other risk factors for osteoporosis.
 Aluminum and magnesium
• Aluminum and magnesium are unlikely to be used solely as supplements;
however, they are found in common over-the-counter antacid products.
• Like calcium, they can bind to vulnerable medications, decreasing their
bioavailability and lessening their efficacy.
• Fluoroquinolone and tetracycline antibiotics, bisphosphonates, and
levothyroxine may be affected by aluminum and magnesium; therefore,
doses of these drugs should not be taken within two hours of aluminum or
magnesium consumption.
• If the patient is not responding to therapy as expected, the pharmacist
should recommend that the aluminum or magnesium product be
discontinued and an alternative identified.

Iron
• Iron supplements are needed if the body cannot produce a sufficient amount of red blood cells. Lack of iron may lead to tiredness, shortness of
breath, decreases in physical performance, learning problems, and an increased risk of infection.
Patients taking iron supplements or multivitamins that contain iron should be instructed to avoid taking their supplement within two hours of a
dose of tetracycline or fluoroquinolone antibiotics, digoxin, or levothyroxine.
• In addition, patients taking both calcium and iron supplements should be informed that because these supplements compete for absorption,
they should be dosed at different times of the day.

• Iron salts can also interfere with the absorption of levodopa, decreasing peak levels by 55% and area under the curve by 51%.
• If the patient is experiencing breakthrough parkinsonian symptoms, iron should be avoided. If this is not possible, the dose of the levodopa
should be increased. Iron can also cause worsening of hypertension in patients taking methyldopa, and concomitant administration is not
recommended.
The absorption of iron can be affected by gastric acidity, and a fair amount of evidence exists to support limited iron absorption in patients
taking proton pump inhibitors and medications that decrease gastric acidity.
• In iron-deficient patients who require proton pump inhibitors, intravenous administration of iron is recommended.
• Interactions between iron and omeprazole, which was recently switched to over-the-counter status, may not be easily identifiable; therefore,
pharmacists should question patients about their consumption of omeprazole and iron supplements.
Potassium
• Although most patients taking potassium supplementation receive this mineral in the form of a prescription
product, some over-the-counter products contain potassium.
• Any medication that increases potassium levels in the body has the potential to interact with supplemental
potassium.
• Patients should use caution when taking extra potassium if they take any of the following prescription
medications: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, digoxin,
indomethacin, prescription potassium supplements, and the potassium-sparing diuretics triamterene or
spironolactone.
• While the amount of potassium found in over-the-counter vitamin and mineral supplements is unlikely to
cause major interactions, the pharmacist should warn patients of the potential for interaction, particularly if
the patient is at risk for renal insufficiency.
• When counseling patients about the importance of avoiding excess potassium, pharmacists should mention
that most common salt substitutes available in supermarkets contain potassium; therefore, these products
should be avoided in patients at risk for hyperkalemia. Salt substitutes contain significantly higher amounts
of potassium than do combination vitamin/mineral supplements sold over-the-counter. For example, a 1/4-
teaspoon serving of NoSalt provides 650 mg of potassium. Considering that a 20-mEq prescription tablet
contains 780 mg of potassium, a patient can easily accumulate potassium if using a salt substitute and thus
should be warned against consuming these products if taking medications that retain potassium.
Conclusion
• There are many different types of drug interactions with vitamins and
minerals, ranging in severity and significance. Patients may not think to
share information with their pharmacist about the vitamins and minerals
they take, or they may feel the substances are harmless and irrelevant to
their medication regimen. Because of the likelihood of an interaction,
pharmacists should question patients not only about the drug allergies
they have but also about the vitamins and minerals they ingest daily.
• Information about the use of vitamins, minerals, herbal products, and
other nutraceuticals should be documented in patients' records for future
reference. In addition, pharmacists should encourage software vendors and
employers to provide fields in their profile systems for over-the-counter
medications and supplements, since these products can impact care and
cause easily avoidable drug interactions that could put the patient at risk
for poor outcomes or adverse effects.