Nutrition & Food Science

Food and drug interactions: its side effects

J.A. Ayo H. Agu I. Madaki
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J.A. Ayo H. Agu I. Madaki, (2005),"Food and drug interactions: its side effects", Nutrition & Food Science,
Vol. 35 Iss 4 pp. 243 - 252
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Food and drug interactions: its Food and drug

interaction: its
side effects side effects
J.A. Ayo and H. Agu
Dept of Food Science and Technology, The Federal Polytechnic, Bauchi, Nigeria
I. Madaki 243
Nutrition/Pharmaceutical Unit, Medical Dept, Nigerian Airforce Base, Jos,
Plateau State, Bauchi, Nigeria
Abstract
Purpose – To enlighten the food consumers and drug users as to some of their incompatibilities.
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Design/methodology/approach – Examples from the literature covering compositions of food-

drug, food-drug interactions, and dietary habits were collected from former works.
Findings – Major side-effects of some diet(food) on drugs include alteration in absorption by fatty,
high protein and fiber diets. Drugs such as methateiate, pyrimethamine, isonicotinic acid and asprin
alter the transportation of some nutrients. Nutrient supplementations was found to be beneficial.
Research limitations/implications – Possible factors affecting the reactions need to be identified.
Practical implications – It helps food consumers and drug users to avoid using some of these
materials and also to adopt nutrient supplementation as a better alternative where possible.
Originality/value – The knowledge helps food technologists, nutritionists, physicians and
pharmacists to serve the public better.
Keywords Drugs, Food safety, Diet, Diseases
Paper type Research paper

Introduction
Diet influences all stages of the life cycle. Despite the physiological decline in organ
function which occurs with aging, food continues to supply nutrients that are needed to
maintain good health and to meet the nutritional requirements of elderly adults (Smith
and Bidlack, 1982).
Throughout life, whenever metabolic processes become errant and disrupt cellular
balance, the chemical properties of drugs are often needed to restore order and health.
Yet, drugs can be hazardous. One specific concern is that these xeriobiotics and their
actions in the body can be altered by nutrients and their dietary components.
In a period in the development of medical care when most diseases are chronic ones
requiring long-term management and drug therapy, it is essential to be aware of the effects
of drugs administered over long periods of time. One of the factors that deserves attention
is the interaction between drugs and the nutritional status of an individual, which was
previouslylittle appreciated and is still poorly understood (Krause and Mahan, 1979).
The frequency of adverse effects arising from food and medication incompatibilities
at every stage of life has not been well documented (Smith and Bidlack, 1982), leaving
the clinical significance of such effects in need of consideration and clarification.
However, an understanding of reported and potential interactions is a step forward in
preventing undesirable and often times serious drug effects, nutritional disorders or
both. This review will serve as a brief introduction to an important topic that should
provide food-for-thought for the nutritionist, toxicologist and food scientist alike.
Nutrition & Food Science
Vol. 35 No. 4, 2005
Dietary habits and drug utilization pp. 243-252
Food consumption patterns vary among individuals each stage of the life cycle. During # Emerald Group Publishing Limited
0034-6659
the early life, the food intake of infants and children is essentially determined by their DOI 10.1108/00346650510605630
 NFS parents. During the adolescent period, dietary habits can change dramatically. As
35,4 teenagers strive for personal independence, they establish control over what is to be
eaten and when, frequently by-passing family influence and preference. Frequent
intake of fast foods and snacking are typical eating behaviours seen at this age level.
It is useful to categorizing the interactions of drugs and nutrients into those by
which drug affect the body’s intake absorption, metabolism and requirement for
244 nutrients:
(1) Alteration of absorption of orally administered drugs by affecting:
. G. I. Transit time and motility;
. G. I. Secretions and pH;
. motility of GI tract;
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. ionization of drug;
. stability of drug;
. solubility of drug; and
. complexing of drug with a dietary components.
(2) Alteration of drugs distribution.
(3) Alteration of drugs metabolism.
(4) Alteration of drugs excretion.
(5) Exertion of antagonistic pharmacological response by zactive substance in
food.
And those by which nutrients or foods affect the absorption, metabolism, action and
excreting drugs:
(1) Alteration of food intake:
. change in appetite;
. changes in sense of taste and smell; and
. nausea and vomiting.
(2) Alteration of nutrient:
. Luminal effects:
— changes in gastrointestinal motility;
— changes in bile acid activity; and
— formation of drug-nutrient complexes.
. Mucosal effects:
— inactivation of absorptive enzyme systems; and
— damage to gastrointestinal mucosal cells.
(3) Alteration of nutrient metabolism and utilisation.
(4) Alteration of nutrient excretion.
Adult food habits, too, are influenced by psychosocial factors. Many adults inflated
concepts regarding the benefits of eccentric dietary habits, including the use of
 idiosyncratic diets for weight-reduction. The elderly are probably the most vulnerable Food and drug
to food and drug interactions, the effects of which may result from many interrelated
conditions. These conditions include normal physiological decline, persistence of
interaction: its
chronic disease, limited nutrient uptake and utilization, and psychological and socio- side effects
economic factors that alter food selection and consumption. Many problems are
compounded further by the large number of drugs prescribed. Because, polypharmacy
is a way of life for most of these patents, drug usage can cause a marginally nourished
individual to become nutritionally deficient if proper guidance is not given with regard
245
to food intake and drug therapy.
Examples of foods that can alter drug absorption include fiber, high-protein diets,
milk and milk products, fat and food in general (Hethocox and Stamaszek, 1974)
(Table I). The presence of food in the stomach, especially if it is fatty, delays gastric
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emptying and the absorption of certain drugs, the plasma concentration of ampicillin
and rifamfiicin may be much reduced if they are taken on a full stomach. More
specifically, calcium e.g. in milk, interferes with absorption of tetracyclius and iron (by
chelation) (Lawrence et al., 1997). In spite of the beneficial effects of fiber for the
regulation of bowel movements and the prevention of constipation and irritable bowls
syndrome, individuals being treated with digoxin need to be aware that meals high in
bran fiber may reduce the amount of drug absorbed (Anonymous, 1982).
Milk and milk products can also decrease drug absorption. Calcium in milk and milk
products forms complexes with tetracycline which inhibit the absorption of both the
drug and the minerals such interactions, however, do not imply that milk or milk
products should be eliminated from the diet; only that the drug be taken when food is not
present in the stomach (Lawrence et al., 1997; Brown, 1995). Milky meals can also inhibit
the absorption of methotrexate, an anticancer drug (Pinkerton et al., 1980). The specific
components in the milky meal that inhibited the absorption of this drug have not yet
been identified, nor has the clinical significance of this interaction been established.
In some instances, it is advantageous to take drugs with specific foods or with
meals. One well known nutrients drug interaction benefits the patient. Cisiseofulvimi, a
drug used to treat fungal infections, is best absorbed after a meal high in fat. Treatment
failure may result if the drug is poorly absorbed, which may occur with low fat or high
protein meals.

Food Drug Effect

High-protein diets Leuodopa, methyldopa Amino acid from dietary protein
inhibit absorption of drugs
Milk and milk products Tetracyline Calcium inhibits drug absorption
Milky meala Methotrexate May inhibit drug absorption
High-fat meal Grisecfulvin Increases drug absorption
Fiber (bran) Digoxin May reduce drug absorption
Food (in general) Nitrofurantoxin Increases bioavailability of the drug
Cimetidine Delay absorption may benefit patient
by maintaining blood concentration
of drug between meals
Erythromycin, penicillin, G, Concomitant intake decreases drug Table I.
Tetracycline lincomycin absorption Effects of various foods
and beverages on drug
Note: aMeals contained milk, cornflakes, white bread, butter and sugar absorption
 NFS Nitrofurantoin, a drug used to treat urinary-tract infections, may also be given with
35,4 food, not only to minimize gastrointestinal irritation but also to increase drug
bioavailability. In the ulcer patient receiving cimetidine, a drug which inhibits gastric
secretions, it also may be advantageous to take the drug with meals. Food apparently
delays drug absorption, an interaction which helps to maintain effective concentrations
of the drug between meals (Spence et al., 1980; Lawerence et al., 1997; Lefkonitze, 1995).
Examples of specific foods that can modify the action of drugs include various
246 vegetables, high-protein diets, salty foods, licerice, citrus juices and caffenie –
containing beverages (Table II). In patients taking oral anticoagulants ingestion of
boiled or fried onions or an increased intake of foods high in vitamin K can increase or
decrease pro thrombin times, respectively (Rubin, 1986).
There is little doubt that certain dietary habits can alter drug utilization. The
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absorption, action and excretion of most drugs are controlled within the milieu of
complex physiological systems which can be altered by varying amounts of certain
foods or beverages, specific foods, unusual diets or non-nutrients in foods. Yet, most
patents who take drugs or parents who administer drugs to their children are given
little information about drugs usage and diet.
Well-known interactions have also been reported between tetracycline and such
minerals as calcium magnesium, zinc, and iron. Any bi-or trivalent cation will form
complexes with the drug, both of which one then poorly absorbed from the
gastrointestinal tracts (Montamat, 1989; Lucas and Sells, 1997). At sick are those
individuals treated for iron-deficiency anemia who are also taking tetracycline for
acne other ailments. Roe (1981) suspects that the drug is best absorbed when taken at
least three hours before or after the intake of any iron, rich or iron-fortified food.

Food Drug Effect

Vegetables Warfarin May increase fibringytic activity of drug
Boiled or fried onions Warfarin Vegetables rich in vitamin K may
Broccol, cabbage, turnip inhibit hypoprothrombinemic response
greens, lectuce to oral anticoagulants
Protein or charcoal broiled Theophylibne May increase plasma half life of drug
meats
Salty foods, salt Lithium Increased inake of sodium may reduce
therapeutic response to drug. Low SaH
diets may enhance lithium toxicity
Licorice Diuretics (chlorthalidone, Cilycyrrhizic acid in licorica tends to
furosemide, metolazone, induce hypokalemia and sodium
thiazides) retention, ingestion may complicate
antitypertensive drug therapy
Digoxin Licorice-induced hypokalemia may
cause digitalis toxicity
Beverages
Green tea Anticoagulants Large intake may inhibit hypoprothrom-
binemic response of drugs
Theophylline Increase intake may enhance drug side
effect (nervousness, insomnia)
Neuroleptic agents Increase intake may result in a large
Table II. variation in plasma concentration of
Effects of various foods drug
and beverages on drug Citrus Quinidine Excessive intake may incrrease blood
action levels of drugs (alkalinization of urine)
 Drugs that affect the metabolism and excretion of nutrients Food and drug
Antivitamins
Drugs that interfere with the action of a vitamin with its enzymes can be
interaction: its
antivitabolites, antivitamins or enzyme inducers. Antivitamins and antimetabolities, side effects
with structures similar to those of the real vitamins and metabolites, can block
enzymatic reactions. The enzymes take up the antivitamin or antimetabolite instead of
the actual vitamin or metabolite (Krause and Mahan, 1979). Cancer chemotherapheutic
agents work on this principle. The antivitamins are taken up by the most rapidly 247
growing cells in the body, the cancer cells which die or malfunction when the
antivitamin does not function like the real vitamin. Common antivitamins are the folate
antagonists, methotrexiate and pyrimethamine (Roe, 1981). Nethotrexate is used to treat
leukemia, choriocarcinoma and psoriasis that is resistant to other forms of therapy.
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Pyrimethanine is used in the treatment of chloroquine – resistant malaria and oculcur

toxoplasmosis. These drugs act as folic acid analogs and are bound to the
dehydrofolate reductase enzyme instead of folic acid. Folic acid is then unable to bind
with enzyme and is put out of the metabolic system and excreted (Lucas and Sells,
1997). Without the real folic acid, deoxyribonucleic acid (DNA) synthesis, which
depends on the presence of folic acid is inhibited, cell replication stops and the cell dies
(Streif, 1981).
A drug may also affect the metabolism of a nutrient by forming a complex with it,
making it unavailable for use by the body. Isonicotinic acid hydrazide (INH) fucntions
in this manner. This drug, used in the long term treatment of tuberculosis, forms a
complex with pyridoxine (Vitamin B6) with the result that the pyridoxine is excreted in
the urine and is not used by the body. A dose of 50 mg of vitamin B6 daily will protect
against vitamin B6 deficiency when the patient is taking one of these drugs (Kruse and
Mahan, 1979; Rolf and Harper, 1995).

Excretion of Nutrients
Drugs act to increase the excretion of a nutrient by displacing the vitamin from its
binding site on a plasma protein. If unbind to a protein, the vitamin will be filtered
through the kidneys and excreted (Roe, 1981). Aspirin may alter the transport of folate
by competing for sites on the serum protein that transport folate and thus folate is
excreted (Roe, 1981). Drugs can also increase the excretion of a nutrient by decreasing
its reabsorption by the kidneys. Oral dimretics such as furosemide, ethacrynic acid and
triameterene can produce significant hypercalciuria by reducing reabsorption of
calcium from the convoluted tubule in the kidney (Krause and Mahan, 1979). See
Table III for a synopsis of the nutritional implication of the use of selected drugs.

Nutrient supplementation and drug

There are certain instances when the use of nutrient supplements may be
advantageous to the overall nutritional status of the medicated individual. Patients
treated with the diuretic triameterence (a weak folic acid antagonist) may benefit from
folic acid supplementation. If signs of drug induced folic acid deficiency develop. On
the other hand, if folacin deficiency develops in epileptic patients receiving
phenmytoin, folacin must be cautiously administered, as the vitamin may decrease the
effectiveness of the drug and result in lost of seizure control (Alter et al., 1971; Smih and
Bidlack, 1982; Chien et al., 1975).
Other interesting benefits of vitamins supplementation are seen in patients treated
with the antitubercular agent isoniazide or the anti-hypertesive agent hydralazine.
 NFS Drug Mechanism
35,4 Analgesics
Alcohol Toxic effect on intestinal
mucosa. Impairs pancreatic
enzyme secretion.
Aspirin (salicylates) Block uptake of vitamin C
248 by platelets.
Colchicine Decreases activity of
intestinal disaccharidases.
Damages G.I. mucosa by
blocking mucosal cell
replication
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Amphetamines Decrease appetite
Dextroamphetamine
Methylphenidate
Antacids
Aluminum hydroxide Decreases absorption of
phosphate
Others Basic environment
inactivates thiamin
Anticonvulsants
Phenobarbital Increase turnover of
Phenytoin vitamin D, may block
hydroxylation of vitamin D.
Primidone
Barbiturates Accelerate inactivation of
vitamin D
Antidepressants
Lithium carbonate May increase appetite
Antivitamins
Methotrexate Inhibits dihydrofolate
reductase
Pyrimethamine Causes gastrointestinal
mucosal injury
Antimicrobials
Chloramphenicol Decreases protein
synthesis by blocking
mRNA-ribosome bond
Penicillin Carries potassium with it
into urine
Tetracyclines Chelate divalen ions.
May decrease synthesis of
mucosal iron-carrier protein
Deceases activity of
Neomycin disaccharidases.
Causes mucosal injury.
Precipitates bile acids and
disrupts micelle formation
Table III.
Effects of some drugs
on nutritional status
Nutritional implication
Decreased absoprtion of thiamin, folic
acid, vitamin B12.
Increased urinary excretion of
magnesium and zinc
Decreased serum folate.
Increased urinary excretion of vitamin C.
Decreased absorption of vitamin B12,
fat, carotene, sodium, potassium,
lactose, xylose, protein.
Decreased serum cholesterol, carotene
and vitamin B12.
Decreased caloric intake and possibly
reduced growth
Phosphate depletion
Inadequate amount of thiamin
Decreased serum levels of folate,
vitamin B12, pyridoxine, 25-
hydroxyvitamin D3 and calcium
Possible osteomalacia
Decreased absorption of thiamin.
Increased urinary excretion of vitamin C.
Decreased serum vitamin B12.
Possible weight gain
Malabsorption of vitamin B12, folate,
fat and xylose.
Weight loss, diarrhea, nausea,
anorexia, vomiting, gingivitis,
stomatitis
Possibly increased need for riboflavin,
pyridoxine and vitamin B12. Possible
peripheral neuritis, optic neuropathy.
Hypokalemia
Decreased absorption of clacium, iron,
magnesium, xylose, amino acids and fat.
Increased urinary excretion of viamin C,
riboflavin, nitrogen colic acid and
niacin.
Decreased synthesis of vitamin K by
intestinal bacteria.
Decreased absorption of fat,
carbohydrate, protein, fat soluble
vitamins, vitamin B12, calcium, iron
(Continued)
 Drug Mechanism
Antitubercular Agents Affects mucosal transport
mechanism.
Para-aminosaclicylic acid
Isonicotinic acid Structurally related to
hydrazide (INH) pyridoxine and niacin
Cycloserine Acts as a pyridoxine
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antagonist
Cathartics Can cause intestinal
hyperperistasis.
May irritate intestine
Chelating agents
Penicillamine Chelates with pyridoxine.
Chelates with zinc and
copper.
Corticosteroids
Phenobarbital Stimulate protein
catabolism.
Phenytoin Depress protein synthesis.
Primidone
Diuretics
Furosemide
Mercurials
Thiazides May increase intestinal
calcium absorption or
increase bone resorption
Triamterene Competitive inhibition of
dihydrofolate reductase,
reduces activation of folic
acid.
Nutritional implication Food and drug
Decreased absorption of vitamin B12, interaction: its
iron, folate, fat and xylose. side effects
Possible peripheral neuritis.
Decreased intestinal mucosal
disaccharidases.
Increased urinary excretion of
pyridoxine. 249
Causes pyridoxine depletion.
Can cause polyneuropathy,
megaloblastic anemia.
Causes niacin depletion.
Decreased protein synthesis.
May decrease serum folate, vitamin
B12 and pyridoxine.
Can cause steatorrhea.
Can increase intestinal calcium and
potassium loss.
Decreased glucose absorption.
Increased urinary excretion of
pyridoxine, zinc and copper.
Can cause pyridoxine depeltion.
Decrased absorption of calcium and
phosphorus.
Increased urinary excretion of vitamin
C, calcium, potassium, zinc and
nitrogen.
Decreased serum zinc.
Increased blood glucose, serum
triglycerides, serum cholesterol.
Increased excretion of calcium,
magnesium and potassium.
Decreased serum magnesium and
potassium.
Decreased carbohydrate tolerance.
Increased urinary excretion of thiamin,
magnesium, calcium and potassium.
Possibly induced magnesium depletion
and bone resorption.
Increased urinary excretion of
potassium, magnesium, zinc and
reboflavin.
Decreased carbohydrate tolerance.
Possible potassium and magnesium
depletion.
Decreased serum folate, serum
viamin B12.
Possibly increased calcium
excretion.
(Continued) Table III.
 NFS Drug Mechanism
35,4 Hypocholesterolemics
Cholestyramine Binds bile salts and
disrupts micelles.
Binds intrinsic factor at
ileal pH.
250
Clofibrate May decrease activity of
intestinal disaccharidases.
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Hypotensive agents
Hydralazine Inactivates pyridoxine.
May chelate trace metals
Laxatives
Mineral oil Dissolves fat-soluble
vitamins.
L-Dopa (levodopa) Pyridoxine involved in
metabolism of L-Dopa.
Antagonizes pyridoxine.
Oral Contraceptives May increase catabolism,
decrease absorption or
alter tissue uptake or
vitamin C.
May inhibit folate
conjugase.
May increase transport
proteins for vitamin A.
Estrogens increase he rate
of conversion of typtophan
to niacin
Sedative-hypnotics
Glutethimide Possibly increases
inactivation of 25-hydroxy
vitamin D3.
Sulfonamides
Salicylazosulfapyridine
(Azulfidine).
Other sulfonamides
Tranquilizers
Chlorpromazine Can reduce physical
Table III. activity.
Nutritional implication
Decreased absorption of cholesterol,
vitamin A, D. K and B12, folate, fat,
medium-chain triglycerides (MCT),
glucose, xylose, carotene, iron.
Decreased calcium absorption.
Decreased serum calcium and
vitamin B12.
Increased urinary calcium.
Decreased taste acuity, unpleasant
after taste.
Decreased absorption of carotene,
glucose, iron, MCT, vitamin B12.
Increased excretion of pyridoxine,
pyridoxine depletion.
Possible peripheral neuritis.
Decreased absorption of carotene,
vitamins A, D, E and K, calcium and
phosphate.
Possible polyneuropathy related to
pyridoxine depletion.
Increased need for ascorbic acid and
pyridoxine.
Decreased absorption of tryptophan
and other amino acids.
Increased urinary excretion of sodium
and potassium.
Altered typtophan metabolism.
Decreased serum vitamin C levels.
Possibly decreased serum vitamin B12,
folate, pyridoxine, riboflavin,
magnesium and zinc.
Increased hemoglobin, hematocrit,
serum levels of vitamins A and E,
total lipids, triglycerides, iron, total
iron-binding capacity (TIBC) and
plasma copper.
Possible polyneuroopathy, peripheral
neuritis and megaloblastic anemia.
Increased vitamin D turnover.
Increased bone resorption.
Decreased absorption of folate.
Decreased serum folate and serum iron.
Decreased sources of folate, vitamin K,
B vitamins from intestinal bacterial
synthesis
Possible weight gain.
 Peripheral neuropathy (numbness, turgling and weakness of the extremities) may Food and drug
develop in individuals receiving either of these drugs. This neurological side effect can be interaction: its
corrected by giving pyridoxine supplements (Raskin and Fishman, 1965; Snider, 1980).
If the drug should antagonize nutrient function, nutrient supplementation may be side effects
beneficial to the patient. However, nutritional self medication can be potentially
hazardous to the health of drug users, as various nutrients in supplements can increase
drug action, aggravates drug side effects or interfere with the effectiveness of the drug 251
in the management of various diseases.

Need to increase knowledge and educate consumers

The interactions between drugs and various components in the diet are in part
responsible for the erratic drug responses observed in patients at different age levels.
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Because of the diversity of food consumption patterns among individuals and the
widespread use of drugs, an array of varied and complicated side effects can occur.
When vitamins, minerals, or other food components alter drug utilization or when drug
induce nutritional deficiencies, either effect poses a risk to the patient. To reduce this
risk, individual taking drugs need to make rational decisions about the consumption of
various food items.
We need to increase our knowledge of the interactive components in food that alter
drug efficacy and to encourage education about nutrient and drug incompatibilities. It
will be through such efforts by food scientists, nutritionists, physicians, and
pharmacists that the interest of the public will be served.

References
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 NFS Spence, R.W., Creak, D.R. and Celestin, L.R. (1980), ‘‘Influence of meal on the absorption of
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Further reading
Baylis, E.M., Crowley, J.M., Preece, J.M., Sylvester, P.E. and Marks, V. (1971), ‘‘Influence of folic
acid on blood phenytoin levels’’, Lancet, Vol. 1, pp. 62.
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1. Matthias Strupler, Claudio PerretMedical Issues, Pharmacology and Nutrient Interactions 153-166.
[CrossRef]
2. Ayantunji GbadamosiUEL Business School, University of East London, London, UK Ojo Olukayode
IwaloyeSchool of Government, Leadership and Management, Macau Inter‐University Institute, Macau,
SAR, China David BamberHope Business School, Liverpool Hope University, Liverpool, UK. 2009. An
exploratory study of students' consumption of non‐alcoholic beverages in Nigeria. Nutrition & Food Science
39:6, 609-618. [Abstract] [Full Text] [PDF]
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