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Purpose: To collate evidence on nutrient deficiencies caused by drugs. Design: Search of Medline and other databases, and published literature. Materials and methods: Medline, Scirus and Google Scholar databases, journal articles and books. Results: There is evidence that many drugs, medicinal or recreational, produce deficiencies in vitamins, minerals, fatty acids and/or amino acids. Some drugs cause multiple deficiencies. They may reduce conversion of vitamins to their active forms, or inhibit the production of important metabolites. By killing beneficial bacteria in the gut, they may cause vitamin deficiency. They may reduce absorption, or cause excretion of nutrients. Conclusions: Many drugs have been identified, which appear to cause deficiencies in essential nutrients and their metabolites. Nutrients could be prescribed with drugs, to limit the damage done, provided that this does not undermine the action of the drugs. Further research is needed to confirm the results of those studies that have been carried out, and to find out about nutrient depletion from new drugs.
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Drugs as anti-nutrients
Margaret Moss a
aMA (Cantab), UCTD (Manchester), DipION, CBiol, MIBiol, Director of the Nutrition
and Allergy Clinic, 11 Mauldeth Close, Heaton Mersey, Stockport, Cheshire SK4
First Published on: 01 June 2007
To cite this Article: Moss, Margaret (2007) 'Drugs as anti-nutrients', Journal of
Nutritional & Environmental Medicine, 16:2, 149 — 166
To link to this article: DOI: 10.1080/13590840701352740
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Downloaded By: [Moss, Margaret] At: 23:47 1 July 2008
Drugs as anti-nutrients
MIBIOL, Director of the Nutrition and Allergy Clinic
11 Mauldeth Close, Heaton Mersey, Stockport, Cheshire SK4 3NP
Purpose: To collate evidence on nutrient deficiencies caused by drugs.
Design: Search of Medline and other databases, and published literature.
Materials and methods: Medline, Scirus and Google Scholar databases, journal articles and books.
Results: There is evidence that many drugs, medicinal or recreational, produce deficiencies in
vitamins, minerals, fatty acids and/or amino acids. Some drugs cause multiple deficiencies. They may
reduce conversion of vitamins to their active forms, or inhibit the production of important
metabolites. By killing beneficial bacteria in the gut, they may cause vitamin deficiency. They may
reduce absorption, or cause excretion of nutrients.
Conclusions: Many drugs have been identified, which appear to cause deficiencies in essential nutrients
and their metabolites. Nutrients could be prescribed with drugs, to limit the damage done, provided
that this does not undermine the action of the drugs. Further research is needed to confirm the
results of those studies that have been carried out, and to find out about nutrient depletion from new
Key words: drug–nutrient interaction, drug–vitamin interaction, drug–mineral interaction, nutrient
deficiency, vitamin deficiency, mineral deficiency, coenzyme Q10 deficiency
Nutrients are amino acids, vitamins, elements and essential fatty acids that are required by
the body in order to carry out its normal functions. Drugs act by bypassing the normal
processes, and thus often cause side effects. Often drugs act as anti-nutrients, by causing
deficiency in essential substances, or by interfering with their functions. People who are
already deficient, or whose nutritional status is marginal are likely to be more susceptible to
side effects of drugs. However, some drugs increase the levels of certain nutrients.
Drugs may affect nutritional status in different ways. They can alter intake, absorption,
metabolism, utilisation or excretion [1,2]. Many people take several drugs at a time, and no
one knows what the interactions of all these drugs are. These drugs may be medicinal, or
recreational. Research on drug–nutrient interactions is very limited. I shall list here some of
the information that has been reported so far, on possible deficiencies in nutrients, gut
bacteria and hormones caused by drugs. Further research is needed in some cases, to check
the findings. Research trials may produce conflicting information. Sometimes the research
Correspondence: Margaret Moss, MA (Cantab), UCTD (Manchester), DipION, CBiol, MIBiol, Director of the Nutrition and
Allergy Clinic, 11 Mauldeth Close, Heaton Mersey, Stockport, Cheshire SK4 3NP.
Journal of Nutritional & Environmental Medicine
May 2007; 16(2): 149–166
ISSN 1359-0847 print/ISSN 1364-6907 online #2007 Informa UK Ltd
DOI: 10.1080/13590840701352740
Downloaded By: [Moss, Margaret] At: 23:47 1 July 2008
has been carried out into only one drug in a group, and we can only suspect that others have
the same effect. Some individuals are more susceptible to loss of nutrients than others, and
they are more likely to suffer from side effects. Research that has only been carried out on
laboratory animals needs to be followed by studies on humans.
Prescription of drugs should be based on cost–benefit considerations. There are
occasions where the side effects of a drug are acceptable, because of the gravity of the
disease, and the lack of any other means of combating it effectively. However, there is no
point in taking a drug if the expected side effects are worse than the disease or if the disease
can be treated effectively without side effects. Short courses of drugs are usually less of a
threat than long-term courses. Often illness is caused by nutrient deficiency, and unless the
deficiency is treated, there may be more serious consequences later on. Using drugs to
cover up deficiency symptoms can therefore be dangerous.
In some cases, side effects of drugs may be reduced by taking a supplement of a relevant
nutrient. However, in other cases this is not recommended, as it may make the drug useless.
For example, carbamazapine and phenobarbitone appear to lower folic acid levels [3], but
giving too much folic acid may inactivate the drug [4].
Drugs have a generic name, and sometimes several other names given by different
manufacturers. One manufacturer may use different names in different countries. This can
make it difficult to check on drug–nutrient interactions.
It may be thought that people living in affluent countries are not subject to nutrient
deficiencies. However, a combination of genetic diversity in nutrient requirements, unwise
food selection or preparation, intensive exercise, infection, and the use of anti-nutrient
drugs may lead to deficiency symptoms.
Materials and methods
A search was carried out of the literature on drug-nutrient interactions, using books and the
Medline, Scirus and Google Scholar databases, to collect information on anti-nutrient
drugs. ‘Drug–nutrient interactions’, ‘Drug–vitamin interactions’, and ‘Drug–mineral
interactions’ were used as general search terms. Specific searches, for example for
‘Statin, coenzyme Q10’, or ‘Seelig, magnesium deficiency’ were also used.
Many drugs were identified, which are thought to act as anti-nutrients (Table I).
Deficiencies may be caused in many nutrients. Elements may be affected, including
calcium, chlorine, copper, iron, magnesium, manganese, nitrogen, phosphorus, potassium,
selenium, sodium and zinc. Vitamins A, B1, B2, B3, B6, B12, C, D, E and K, folic acid and
biotin may also be affected, as well as carotene and coenzyme Q10. Amino acids involved
may include L-carnitine, L-leucine, and the sulphur amino acids. Fat and carbohydrate are
also mentioned in the literature, as well as beneficial gut bacteria. Hormones may be
involved, including DHEA (dehydroepiandrosterone) and melatonin.
A nutritional approach aims at finding out which biochemical systems are failing to work
properly, and rectifying them. This is a very different process from the use of drugs or even
herbs, which do not usually enhance an existing biochemical pathway. They are more likely
to divert the body down a new pathway, which was not part of its design. This can lead to
150 M. Moss
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Table I. Drugs that may reduce the absorption or activity of nutrients or normal body constituents.
Drug or type of drug Possible deficiency or interference Reference
Adriamycin (Doxorubicin) Coenzyme Q10 [5]
Vitamin B2 [6]
Aluminium hydroxide Calcium [7]
Phosphorus [8]
Vitamin A [8]
Aminoglycosides, e.g. Gentamycin Calcium [8]
Magnesium [9]
Potassium [8]
Vitamins B1, B2, B3, B6, [10]
Vitamins B12 and K [10]
Aminopterin Folic acid [8]
Vitamin B12 [8]
Amitriptylene Sodium [8]
Vitamin B2 [11,12]
Amoxicillin (Amoxil) L-leucine [13]
Amphotericin B (Fungizone) Calcium [10]
Magnesium [9,14]
Potassium [8]
Antacids Folic acid [15]
Calcium [7,16–19]
Copper [8]
Phosphate [8,10]
Vitamin A [8]
Vitamin B12 [20]
Antibiotics Beneficial gut bacteria [4,21,22]
Vitamin K [4]
L-leucine [13]
Biotin [21–23]
Anticonvulsants Biotin [24,25]
Folic acid [3,25]
Vitamins B2, B6, B12 [25]
Vitamins D, E [25]
Vitamin K [8]
L-carnitine [26]
Aspirin Folic acid [27]
Iron [10]
Vitamin C [8]
Vitamin E [10]
Zinc [4]
Potassium [10]
Atorvastatin Coenzyme Q10 [28]
AZT (Zidovudine) L-carnitine [4]
Copper [29]
Vitamin B12 [4]
Zinc [29]
Beta-adrenergic blocking agents Coenzyme Q10 [5]
Bile acid sequestrants Calcium [4]
Carotenoids [30]
Folic acid [4]
Vitamins A, D, E, K [4]
Zinc [4]
Bisacodyl (Dulcolax, stimulant laxative) Potassium [31]
Boric acid Riboflavin [32,33]
Caffeine Calcium [34]
Drugs as anti-nutrients 151
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Table I. Continued.
Drug or type of drug Possible deficiency or interference Reference
Calomel Phosphorus [8]
Captopril (Capoten – ACE inhibitor) Zinc [35]
Sodium [8]
Carbamazepine Folic acid [3]
Sodium [8]
Carbenoxolone Potassium [8]
Cephalexin L-leucine [13]
Cephalosporins (Antibiotics) Vitamin K [8]
Chemotherapy Magnesium [36,37]
Vitamin B2 [6]
Taurine [4]
Many other nutrients [4]
Chloramphenicol Folic acid [8]
Chloride Calcium [38]
Magnesium [38]
Chlorpromazine Vitamin B2 [11,12,32,39,40]
Chlorpropamide Sodium [41]
Potassium [10]
Chlorthalidone (Chlortalidone) Zinc [42,43]
Potassium [10]
Cholestyramine Carotenoids [8]
Fat [8]
Folic acid [44]
Calcium [10,44]
Iron [44]
Magnesium [10]
Phosphorus [10]
Zinc [10]
Vitamin A [8]
Vitamin B12 [44]
Vitamins D, E [8]
Vitamin K [45]
Cimetidine (Tagamet) Iron [4]
Zinc [46]
Folic acid [15]
Vitamin B12 [4]
Vitamin D [47]
Cisplatin (Platinol) Magnesium [48]
Clofibrate (Atromid-S) Vitamin B12 [4]
Vitamin E [8]
Clozapine Selenium [10]
Colchicine Fat [8]
Beta carotene [8]
Potassium [8]
Sodium [8]
Vitamin B12 [8]
Colestipol (Colestid) Beta carotene [30]
Folic acid [44]
Iron [44]
Vitamin A [8]
Vitamin B12 [44]
Vitamins D, E and K [8]
Conjugated oestrogens (Premarin) Vitamin B6 [4]
152 M. Moss
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Drug or type of drug Possible deficiency or interference Reference
Corticosteroids Calcium [10]
DHEA [4]
Magnesium [10]
Melatonin [4]
Potassium [4]
Folic acid [49]
Vitamin B6 [4]
Vitamin B12 [49]
Vitamins C, D, K [4]
Vitamin E [10]
Selenium [8]
Zinc [10]
Cyclophosphamide (Cytoxan, Neosar) Sodium [8]
Cycloserine (Seromycin) Calcium [4]
Folic acid [4]
Magnesium [4]
Vitamins B6, B12, K [4]
Cyclosporin (Sandimmune, Neoral) Magnesium [50–52]
Dicoumarol Vitamin K [8]
Digitalis (Digoxin, Lanoxin, Digitoxin) Magnesium [48,53]
Calcium [8]
Sodium [53]
Potassium [48,53]
Disopyramide phosphate Magnesium [8]
Distal tubule diuretics Zinc [42,43]
Magnesium [54–58]
Diuretics Magnesium [48,54,55–59,61–64]
Potassium [48,59,60]
Zinc [42,43]
Vitamin B1 [65]
L-dopa ( Levodopa, Dopar, Larodapa) Vitamin B6 [8]
Potassium [60,66]
Doxycycline Vitamin K [4]
Dymelor Coenzyme Q10 [8]
Edetate calcium disodium (EDTA) Calcium [8,10]
Zinc [8,10]
Erythromycin Calcium [4]
Magnesium [4]
Folic acid [4]
Vitamins B6 and B12 [4]
Ethacrynic acid Calcium [8]
Magnesium, potassium [8]
Ethanol Vitamin A [10]
Vitamin B1 [10]
Vitamin B2 [67]
Vitamin B6 [10]
Iron, zinc [10]
Ethionamide Vitamin B6 [8]
Etodolac (Lodine) Iron [4]
Famotidine (Pepcid – antacid) Copper [4]
Folic acid [4]
Calcium, iron [10]
Vitamin B12 [4]
Table I. Continued.
Drugs as anti-nutrients 153
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Drug or type of drug Possible deficiency or interference Reference
Fibric acid derivatives Folic acid [68]
5-Fluorouracil (5-FU, Efudex, Fluoroplex) Vitamin B1 [8]
Fluoxetine (Prozac – SSRI) Melatonin [69]
Potassium [10]
Sodium [70]
Furosemide (Frusemide, loop diuretic) Calcium [8]
Magnesium [9,61]
Potassium [8]
Vitamin B1 [8]
Vitamins B6 and C [71]
Gemfibrozil (lipid regulator) Coenzyme Q10 [5]
Gentamycin (Garamycin) Calcium [10]
Magnesium [72]
Potassium [72]
Vitamin B6 [4]
Glutethimide Vitamin D [8]
Glyburide (Glibenclamide, Diabeta, Micronase) Coenzyme Q10 [8]
Gold Selenium [8]
Haloperidol (Haldol) Iron, potassium, sodium [4]
Heparin Vitamin D [73]
Histamine H
-antagonists Iron [74]
Zinc [46]
Folic acid [10]
Vitamin B12 [74]
Hydralazine (Apresoline) Vitamin B6 [75]
Hydrazine Vitamin B6 [8]
Ibuprofen (Advil, Motrin, Nuprin) Iron [4]
Imipramine Vitamin B2 [11,12]
Indapamide Chloride [76]
Sodium, potassium [76]
Indomethacin (Indocin) Calcium [4]
Iron [77]
Folic acid [10]
Vitamin C [4]
Phosphate [10]
Isoniazid (INH, Laniazid, Rifamate, Rimactane) Calcium [10]
Folic acid [4]
Magnesium [10]
Vitamins B3, B6 [10]
Vitamin B12 [4]
Vitamin D [47]
Vitamins E, K [4]
Lansoprazole (Prevacid, proton pump inhibitor) Beta carotene [4]
Vitamin B12 [4]
Calcium [10]
Laxatives Potassium [31,60,78]
Lithium carbonate Sodium [79]
Loop diuretics Magnesium [48,55–58,61,62]
Potassium [48]
Vitamins B1, B6, E [10]
Table I. Continued.
154 M. Moss
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Drug or type of drug Possible deficiency or interference Reference
Losartan (Cozaar, angiotensin-II receptor
Calcium [80]
Chloride [80]
Magnesium [80]
Potassium [80]
Sodium [80]
Phosphate [80]
Lovastatin (Mevacor) Coenzyme Q10 [81,82]
Magnesium hydroxide (Milk of Magnesia) Iron [10]
Phosphate [10]
Folic acid [15]
Mannitol Sodium [8]
Metformin (Glucophage) Folic acid [4]
Vitamin B12 [10]
Methotrexate (Folex, Rheumatrex) Calcium [10]
Folic acid [83]
Methyldopa (Aldomet) Vitamin B12 [4]
Mineral oil Beta carotene [84]
Calcium, phosphorus [10]
Potassium [10]
Vitamins A, K [10]
Vitamins D, E [4]
Neomycin Carbohydrate [4]
Beta carotene [4]
Fats [4]
Folic acid [4]
Calcium [10]
Iron [10]
Magnesium, [8]
Potassium [8]
Nitrogen [8]
Sodium [8]
Vitamin A [10]
Vitamin B6 [4]
Vitamin B12 [10]
Vitamin D [4]
Vitamin K [8]
Nicotinamic acid (niacin) Folic acid [68]
Nitrous oxide Folic acid [85]
Vitamin B12 [85–87]
Non-steroidal anti-inflammatory analgesics Folic acid [88]
Iron [89]
Omeprazole (Prilosec – proton pump inhibitor) Beta carotene [90]
Vitamin B12 [91]
Oral contraceptives Magnesium [92]
Manganese [4]
Zinc [10]
Folic acid [93]
Vitamins B1 [4]
Vitamin B2 [10]
Vitamin B3 [4]
Vitamin B6 [94]
Vitamin B12 [10]
Vitamin C [4]
Table I. Continued.
Drugs as anti-nutrients 155
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Drug or type of drug Possible deficiency or interference Reference
Orlistat Fat [95]
Vitamin E [95]
Pancreatic extract Folic acid [96]
Para-aminosalicylic acid Fat [8]
Folic acid, vitamin B12 [8]
Paracetamol (acetaminophen) Sulphur amino acids [97]
Phosphate [98]
Paroxetine (Paxil – SSRI) Sodium [70]
D-Penicillamine (Cuprimine, Depen) Copper, sodium [4]
Vitamin B6 [99]
Zinc [99]
Magnesium [99]
Pentamidine Calcium [10]
Folic acid [8]
Phenelzine (Nardil) Vitamin B6 [100]
Phenformin Coenzyme Q10 [8]
Vitamin B12 [8]
Phenobarbital (Phenobarbitone) Calcium [10]
Folic acid [3]
Vitamin D [8]
Phenolphthalein Calcium, potassium [8]
Vitamin D [8]
Phenothiazines Coenzyme Q10 [8]
Vitamin B2 [10]
Phenylbutazone Folic acid [8]
Phenytoin (Epanutin) Calcium [10]
Folic acid [101]
Vitamins B1, B12, K [10]
Vitamin D [8]
Potassium chloride Vitamin B12 [8]
Potassium sparing diuretics Folic acid [10]
Pravastatin (Pravachol) Coenzyme Q10 [82,102]
Prednisone Calcium [103]
Prednisolone Potassium [10]
Primidone Folic acid [8]
Vitamin D [8]
Probucol Carotenoids [8]
Vitamin E [8]
Procarbazine Vitamin B6 [8]
Progesterone Folic acid [8]
Vitamin B6 [8]
Propranolol (Inderal) Coenzyme Q10 [4]
Pyrazinamide Vitamin B6 [8]
Pyrimethamine (anti-malarial) Folic acid [8]
Quinidine sulphate Magnesium [8]
Ranitidine (Zantac) Iron [46]
Zinc [46]
Vitamin B12 [8]
Selective Serotonin Reuptake Inhibitors (SSRIs) Sodium [70,104]
Melatonin [69]
Sennoside Potassium [31]
Simvastatin (Zocor) Coenzyme Q10 [105]
Vitamin E [105]
Beta carotene [105]
Table I. Continued.
156 M. Moss
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Drug or type of drug Possible deficiency or interference Reference
Sodium bicarbonate Folic acid [8]
Iron [4]
Potassium [10]
Sodium sulphate Potassium [8]
Spironolactone (Aldactone) Potassium, sodium [8]
Stanozolol (Winstrol) Iron [4]
Statins (HMG-CoA Reductase Inhibitors) Selenium [106]
Coenzyme Q10 [5,82,102,105]
Vitamin E [105]
Beta carotene [105]
Strophanthin Calcium [8]
Sulfamethoxazole (Gantanol) Calcium [4]
Folic acid [4]
Magnesium [4]
Vitamins B6, B12, and K [4]
Sulfasalazine (Azulfidine – sulphonamide) Folic acid [83,107]
Sulphonamides Calcium, magnesium, iron [10]
Vitamins B1, B3, B6, B12 [10]
Vitamin K [10]
Tetracyclines (Achromycin, Sumycin – antibiotic) Potassium [8]
Magnesium [10]
Folic acid [4]
Vitamins B2, B6, B12 [10]
Vitamin C [4]
Vitamin K [10]
Beneficial gut bacteria [4]
L-leucine [13]
Theophylline (Slo-Bid, Slo-phyllin, Theo-dur) Magnesium, potassium [4]
Vitamin B1 [108]
Vitamin B6 [108,109]
Thiazide diuretics Magnesium [62]
Potassium, sodium [8]
Zinc [42,43]
Thiosemicarbizide Vitamin B6 [8]
Thyroid hormones Calcium [4]
Tobacco Zinc [8]
Beta carotene [8]
Folic acid, vitamins B6, C, E [8]
Tobramycin (AKTob, Nebicin, Tobrex –
Calcium [110]
Magnesium, potassium [110]
Vitamin K [4]
Tolazamide Coenzyme Q10 [8]
Tolbutamide Sodium [8]
Triamterene (Dyrenium) Calcium [10]
Folic acid [8]
Triazinate Folic acid [8]
Tricyclic antidepressants Coenzyme Q10 [8]
Vitamin B2 [8]
Trientine hydrochloride Iron [8]
Trimethoprim (Proloprim, Trimpex) Folic acid [8]
Calcium, magnesium [4]
Vitamins B6, B12, K [4]
Table I. Continued.
Drugs as anti-nutrients 157
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side effects, sometimes because of causing nutrient deficiencies. Nutrients also interact with
each other, often cooperatively, but sometimes in competition with each other.
Research already carried out suggests that deficiencies are caused by large numbers of
drugs. This is not likely to be a popular topic for sponsoring research. So we probably know
only a small proportion of these interactions.
Diuretics are commonly used drugs, which can cause deficiency of magnesium,
potassium and vitamin B1. There is evidence that magnesium protects against potassium
deficiency, vitamin B1 deactivation, hypertension, intravascular coagulation, diabetes,
congestive heart failure, hyperlipidaemia, atherosclerosis, arrhythmia, myocardial infarc-
tion, preeclampsia, asthma, kidney and liver damage, migraine, multiple sclerosis,
glaucoma, Alzheimer’s disease, recurrent bacterial infection of cavities, fungal infection,
premenstrual syndrome, hypochlorhydria, behavioural disorders, osteoporosis, mood
swings, dental caries, hearing loss, cramps, muscle weakness, impotence, aggression,
cancer, and iron accumulation. A person presenting with what may be temporary
hypertension may find that the drug prescribed makes the condition permanent, as well as
leading to other disastrous consequences [113–126]. Hypertension could be treated with
magnesium, taurine and coenzyme Q10, salt reduction and the avoidance of liquorice.
Alternatively, diuretics could be used together with magnesium and potassium.
A healthy person, with total cholesterol within the reference range, and an excellent
HDL:LDL ratio may be advised to take a statin (HMG-CoA reductase inhibitor) drug, or
choose to buy one over the counter. These drugs cause deficiency of coenzyme Q10, a
nutrient which has been found to protect the heart against stress, and in particular,
oxidative stress [127–128]. Coenzyme Q10 levels tend to drop with age. There is evidence
that coenzyme Q10 protects against arrhythmia and heart failure, and that deficiency can
cause ataxia [129–133]. It may reduce the pro-inflammatory cytokines, TNF-alpha and IL-
6 [134], increase exercise capacity [130] or reduce high blood pressure [130]. It has been
suggested that coenzyme Q10 be administered before cardiac surgery [135]. It may be
taken together with statin drugs, without making them ineffective [136]. The bioavailability
of coenzyme Q10 supplements may depend on their form [137]. As alternatives to statins,
cholesterol may be reduced with sterols in macadamia nuts and oil, glycation of cholesterol
could be reduced by avoiding milk, fruit juice and sugar [138], and anti-oxidants could be
Drug or type of drug Possible deficiency or interference Reference
Valproic acid (Depakene) L-carnitine [111,112]
Copper [4,10]
Selenium [10]
Zinc [10]
Folic acid [8,10]
Ventolin (Albuterol/Salbutamol/Proventil) Calcium [4,10]
Magnesium [4,10]
Phosphate [4,10]
Potassium [4,10]
Vincristine Sodium [8]
Potassium [10]
Warfarin (Coumadin) Vitamin K [8]
Xipamide Magnesium [64]
Zinc [43]
Table I. Continued.
158 M. Moss
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used to reduce oxidation of glycated cholesterol [139]. Nicotinic acid, magnesium,
chromium, lecithin and L-carnitine could be used to improve the total cholesterol:high
density lipoprotein ratio [140–144].
Deficiencies that may be caused by drugs can have diverse effects. Riboflavin (vitamin
B2) deficiency may be caused by adriamycin, amitriptylene, anticonvulsants, boron,
chlorpromazine, ethanol, and oral contraceptives. Riboflavin is needed for electron
transport, which is part of energy production [145–146]. It is also needed for production of
sulphate, which is used in detoxification of amines and phenols [147]. Amitriptylene
prescribed for a person with ME may intensify the exhaustion, unless riboflavin is
supplemented. People with ME often have poor sulphate conjugation [147], and
amitriptylene is likely to make this worse. Riboflavin is also needed to activate vitamin
B6 [148–149]. People may have fits because of lack of activated vitamin B6 [150–152].
Anticonvulsants may worsen this, unless riboflavin is supplemented.
Vitamin D deficiency may be caused by many drugs (Table II), and excessive vitamin A.
Epileptics in Sweden, who may have little exposure to sunlight, and whose food is fortified
with much vitamin A [153], may have their risk of osteoporosis increased by taking
Polypharmacy may cause increased problems. Magnesium deficiency may cause anxiety
[154], hypertension [119,155] and osteoporosis [156–157]. The patient may be prescribed
drugs for each of these results of magnesium deficiency, resulting in a variety of further
deficiencies. These may lead to further symptoms and the provision of more drugs.
Lifestyle may affect responses to drugs. Alcohol is detoxified mainly by alcohol
dehydrogenase, followed by aldehyde dehydrogenase, and oxidase. High alcohol
consumption also requires cytochrome P450 2E1 [158]. An alcoholic may have five times
the normal CYP2E1 [158]. When drinking heavily, processing of other chemicals by
CYP2E1 may be competitively inhibited. However, if admitted to hospital, and unable to
obtain alcohol, he/she may cope very well with medicinal drugs, as the CYP2E1 is still
available to process them [158]. A teetotaller may have a worse reaction to the same drugs.
People who are ill are likely to have nutritional deficiencies that contributed to the illness.
Their responses to drugs will be affected by their genes, their food intake, their use of other
Table II. Drugs which may cause vitamin D deficiency.
Drug Reference
Anticonvulsants [25]
Bile acid sequestrants [4]
Cholestyramine [8]
Cimetidine [47]
Colestipol [8]
Corticosteroids [4]
Glutethimide [8]
Heparin [73]
Isoniazid [47]
Mineral oil [4]
Neomycin [4]
Phenobarbital [8]
Phenolphthalein [8]
Phenytoin [8]
Primidone [8]
Drugs as anti-nutrients 159
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drugs, recreational or medicinal, their age and gender, and the stresses to which they are
Diets vary greatly in nutritional content. People who are already deficient will be more
susceptible to the effects of drugs. Those already on drugs causing the same deficiencies,
will be more at risk and those with genetic problems causing deficiency will also be at risk.
People may have atypical forms of enzymes, which are less effective. An example of
biochemical individuality involves the three siblings who consumed much chicken liver
paˆte´. One died of vitamin A toxicity, one was very ill, and the third was apparently
unaffected [159]. Stresses, like pregnancy, grief, infection, surgery, and excessive exercise
contribute to deficiencies. Nutrients are lost in chronic or acute diarrhoea, or excessive
In order to avoid causing nutrient deficiencies when treating or trying to prevent disease,
the following strategies could be considered:
a. Use non-drug treatments when these are available and effective; for example,
supplementing nutrients that are already deficient and making changes to diet and
b. Manufacture drugs together with relevant nutrients where this is possible, so as to avoid
causing deficiency.
c. Prescribe nutrients together with drugs, in separate containers, to avoid causing
deficiency; for example, probiotics could be prescribed at a different time of day from
d. Prescribe smaller quantities of drugs, together with nutrient supplements, where they
will act synergistically.
e. Label drugs clearly, and provide information in drug handbooks, so that the person
prescribing them knows what deficiencies are likely to be produced, whether the
relevant nutrients may be supplemented, and whether there is a level of supplementa-
tion that would inactivate the drug.
f. Require drug companies to fund research on deficiencies caused by their products.
g. Require medical schools to teach nutrition in greater depth, and to emphasize the
nutritional deficiencies which may be caused by drugs.
Many drugs (including some commonly used, some used in combinations, and some
available over the counter) cause deficiencies in nutrients, which can compromise health.
The value of a drug treatment can be weighed against the consequences of deficiencies that
may be caused. Drugs could be prescribed together with relevant nutritional supplements,
where the supplements do not prevent the drug from working [160]. More research needs
to be done, to identify deficiencies caused by drugs, in order to protect the public. This
research could be taught to medical students and to doctors as part of their continuing
professional development.
It is sometimes assumed that people whose diet provides recommended amounts of all
the nutrients will not have deficiencies. Many people in affluent countries take one or more
drugs for long periods of time, and may well have deficiencies in specific nutrients, or
combinations of nutrients. Such deficiencies can lead to life-threatening conditions.
Those whose diets are deficient in essential nutrients, from lack of knowledge, cooking
skills, money or inclination, may well experience side effects from drugs, when better
nourished individuals do not.
160 M. Moss
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I thank the nutritionist, Jan Robertson, with whom I have had lengthy discussions on how
to prescribe nutrient supplements safely to patients already taking drugs.
1. Trovato A, Nuhlicek DN, Midtling JE. Drug–nutrient interactions. Am Fam Physician 1991;44(5):1651–8.
2. White R, Ashworth A. How drug therapy can affect, threaten and compromise nutritional status. J Hum Nutr
Diet 2000;13(2):119–129.
3. Kishi T, Fujita N, Eguchi T, Ueda K. Mechanism for reduction of serum folate by antiepileptic drugs during
prolonged therapy. J Neurol Sci 1997;145(1):109–12.
4. Lininger SW, Gaby AR, Austin S, et al. A–Z Guide to Drug–herb–vitamin Interactions. Roseville, CA, USA:
Healthnotes. Prima Publishing, 1999.
5. Sarter B. Coenzyme Q10 and cardiovascular disease: A review. J Cardiovasc Nurs 2002;16(4):9–20.
6. Pinto J, Raiczyk GB, Huang YP, Rivlin RS. New approaches to the possible prevention of side effects of
chemotherapy by nutrition. Cancer 1986;58(8Suppl):1911–14.
7. Spencer H, Kramer L, Osis D, Wiatrowski E. Effects of aluminium hydroxide on fluoride and calcium
metabolism. J Environ Pathol Toxicol Oncol 1985;6(1):33–41.
8. Werbach MR. Foundations of Nutritional Medicine: A Sourcebook of Clinical Research. Tarzana, CA,
USA: Third Line Press, 1997.
9. Tsau YK, Tsai WY, Lu FL, Tsai WS, Chen CH. Symptomatic hypomagnesemia in children. Zhonghua Min
Guo Xiao Er Ke Yi Xue Hui Za Zhi 1998;39(6):393–7.
10. Boullata JI, Armenti VT (eds). Handbook of Drug–Nutrient Interactions. Totowa, New Jersey, USA:
Humana Press, 2004.
11. Pinto J, Huang YP, Rivlin RS. Inhibition of riboflavin metabolism in rat tissues by chlorpromazine,
imipramine and amitryptyline. J Clin Invest 1981;67(5):1500–506.
12. Pinto J, Huang YP, Pelliccione N, Rivlin RS. Cardiac sensitivity to the inhibitory effects of chlorpromazine,
imipramine and amitriptyline upon formation of flavins. Biochem Pharmacol 1982;31(21):3495–9.
13. Barcina Y, Ilundain A, Larralde J. Effect of amoxicillin, cephalexin, and tetracycline-HCl on intestinal L-
leucine transport in the rat in vivo. Drug Nutr Interact 1988;5(4):283–8.
14. Marcus N, Garty BZ. Transient hypoparathyroidism due to amphotericin B-induced hypomagnesemia in a
patient with beta-thalassemia. Ann Pharmacother 2001;35(9):1042–4.
15. Russell RM, Golner BB, Krasinski SD, Sadowski JA, Suter PM, Braun CL. Effect of antacid and H2
receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med 1988;112(4):458–63.
16. Spencer H, Kramer L. Osteoporosis, calcium requirement, and factors causing calcium loss. Clin Geriatr
Med 1987;3(2):389–402.
17. Spencer H, Kramer L. The calcium requirement and factors causing calcium loss. Fed Proc
18. Spencer H, Kramer L. Osteoporosis: Calcium, fluoride, and aluminium interactions. J Am Coll Nutr
19. Spencer H, Kramer L, Norris C, Osis D. Effect of small doses of aluminium-containing antacids on calcium
and phosphorus metabolism. Arch Intern Med 1983;143(4):657–9.
20. Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr 1999;19:357–77.
21. Dugina NN, Chebotareva TV, Mitrokhin SD. Large intestine dysbacteriosis and therapy efficacy in patients
with respiratory tract tuberculosis in sanatoria. Antibiot Khimioter 2004;49(4):35–8.
22. S
´J, Kos B, Goreta J, Matosˇic
´S. Role of lactic acid bacteria and bifidobacteria in synbiotic effect.
Food Technol Biotechnol 2001;39(3):227–235.
23. Noda H, Akasaka N, Ohsugi M. Biotin production by bifidobacteria. J Nutr Sci Vitaminol (Tokyo)
24. Mock DM, Mock NI, Nelson RP, Lombard KA. Disturbances in biotin metabolism in children undergoing
long-term anticonvulsant therapy. J Pediatr Gastroenterol Nutr 1998;26(3):245–50.
25. Krause KH, Bonjour JP, Berlit P, Kynast G, Schmidt-Gayk H, Schellenberg B. Effect of long-term treatment
with antiepileptic drugs on the vitamin status. Drug Nutr Interact 1988;5(4):317–43.
26. Zelnik N, Fridkis I, Gruener N. Reduced carnitine and antiepileptic drugs: Cause relationship or co-
existence? Acta Paedriatr 1995;84(1):93–5.
Drugs as anti-nutrients 161
Downloaded By: [Moss, Margaret] At: 23:47 1 July 2008
27. Lawrence VA, Loewenstein JE, Eichner ER. Aspirin and folate binding: in vivo and in vitro studies of serum
binding and urinary excretion of endogenous folate. J Lab Clin Med 1984;103(6):944–8.
28. Rundek T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the coenzyme Q10 level in the
blood of patients at risk for cardiovascular disease and stroke. Arch Neurol 2004;61(6):889–92.
29. Baum MK, Javier JJ, Mantero-Atienza E, et al. Zidovudine-associated adverse reactions in a longitudinal
study of asymptomatic HIV-1-infected homosexual males. J Aquir Immune Defic Syndr
30. Probstfield JL, Lin TL, Peters J, Hunninghake DB. Carotenoids and vitamin A: The effect of
hypocholesterolemic agents on serum levels. Metabolism 1985;34(1):88–91.
31. Ritsema GH, Eilers G. Potassium supplements prevent serious hypokalaemia in colon cleansing. Clin Radiol
32. Pinto JT, Rivlin RS. Drugs that promote renal excretion of riboflavin. Drug–Nutrient Interactions
33. Pinto J, Huang YP, McConnell RJ, Rivlin RS. Increased urinary riboflavin excretion resulting from boric acid
ingestion. J Lab Clin Med 1978;92(1):126–34.
34. Harris SS, Dawson-Hughes B. Caffeine and bone loss in healthy postmenopausal women. Am J Clin Nutr
35. Golik A, Modai D, Averbukh Z, et al. Zinc metabolism in patients treated with captopril versus enalapril.
Metabolism 1990;39(7):665–7.
36. Atkinson SA, Halton JM, Bradley C, Wu B, Barr RD. Bone and mineral abnormalities in childhood acute
lymphoblastic leukemia: Influence of disease, drugs and nutrition. Int J Cancer 1998;11:35–9.
37. Guo CY, Halton JM, Barr RD, Atkinson SA. Hypomagnesemia associated with chemotherapy in patients
treated for acute lymphoblastic leukemia: Possible mechanisms. Oncol Rep 2004;11(1):185–9.
38. Kaup SM, Greger JL. Effect of various chloride salts on the utilisation of phosphorus, calcium, and
magnesium. J Nutr Biochem 1990;1(10):542–8.
39. Pinto J, Huang YP, Rivlin RS. Inhibition by chlorpromazine of thyroxine modulation of flavin metabolism in
liver, cerebrum and cerebellum. Biochem Pharmacol 1985;34(1):93–5.
40. Pelliccione N, Pinto J, Huang YP, Rivlin RS. Accelerated development of riboflavin deficiency by treatment
with chlorpromazine. Biochem Pharmacol 1983;32(19):2949–53.
41. Hirokawa CA, Gray DR. Chlorpropamide-induced hyponatremia in the veteran population. Ann
Pharmacother 1992;26(10):1243–4.
42. Reyes AJ, Olhaberry JV, Leary WP, Lockett CJ, van der Byl K. Urinary zinc excretion, diuretics, zinc
deficiency and some side-effects of diuretics. S Afr Med J 1983;64(24):936–41.
43. Reyes AJ, Leary WP, Lockett CJ, Alcocer. Diuretics and zinc. S Afr Med J 1982;62(11):373–5.
44. Leonard JP, Desager JP, Beckers C, Harvengt C. In vitro binding of various biological substances by two
hypocholesterolaemic resins. Cholestyramine and colestipol. Arzneimittelforschung 1979;29(7):979–81.
45. Vroonhof K, van Rijn HJ, van Hattum J. Vitamin K deficiency and bleeding after long-term use of
cholestyramine. Neth J Med 2003;61(1):19–21.
46. Sturniolo GC, Montino MC, Rossetto L, et al. Inhibition of gastric acid secretion reduces zinc absorption in
man. J Am Coll Nutr 1991;10(4):372–5.
47. Bengoa JM, Bolt MJ, Rosenburg IH. Hepatic vitamin D 25-hydroxylase inhibition by cimetidine and
isoniazid. J Lab Clin Med 1984;104(4):546–52.
48. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. A consequence of magnesium deficiency.
Arch Intern Med 1992;152(1):40–5.
49. Frequin ST, Wevers RA, Braam M, Barkhof F, Hommes OR. Decreased vitamin B12 and folate levels in
cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone. J
Neurol 1993;240(5):305–8.
50. June CH, Thompson CB, Kennedy MS, Loughran TP Jr, Deeg HJ. Correlation of hypomagnesemia with the
onset of cyclosporine-associated hypertension in marrow transplant patients. Transplantation 1986;41(1):
51. Thompson CB, June CH, Sullivan KM, Thomas ED. Association between cyclosporin neurotoxicity and
hypomagnesaemia. Lancet 1984;2(8412):1116–20.
52. June CH, Thompson CB, Kennedy MS, Nims J, Thomas ED. Profound hypomagnesemia and renal
magnesium wasting associated with the use of cyclosporine for marrow transplantation. Transplantation
53. Whang R, Oei TO, Watanabe A. Frequency of hypomagnesemia in hospitalized patients receiving digitalis.
Arch Intern Med 1985;145(4):655–6.
54. Leary WP, Reyes AJ. Prophylaxis and treatment of magnesium depletion. S Afr Med J 1983;64(8):281–2.
162 M. Moss
Downloaded By: [Moss, Margaret] At: 23:47 1 July 2008
55. Reyes AJ, Leary WP. Diuretic therapy, magnesium deficiency and lipid metabolism. S Afr Med J
56. Reyes AJ, Leary WP. Magnesium deficiency provoked by diuretics. S Afr Med J 1983;63(11):410–12.
57. Reyes AJ, Leary WP. Cardiovascular toxicity of diuretics related to magnesium depletion. Hum Toxicol
58. Leary WP, Reyes AJ. Diuretic-induced magnesium losses. Drugs 1984;28 Suppl 1:182–7.
59. Dorup I, Skajaa K, Thybo NK. Oral magnesium supplementation restores the concentrations of magnesium,
potassium and sodium–potassium pumps in skeletal muscle of patients receiving diuretic treatment. J Intern
Med 1993;233(2):117–23.
60. Steen B. Hypokalemia—clinical spectrum and etiology. Acta Med Scand 1981;647:61–6.
61. Cohen N, Almoznino-Sarafian D, Zaidenstein R, et al. Serum magnesium aberrations in furosemide
(frusemide) treated patients with congestive heart failure: Pathophysiological correlates and prognostic
evaluation. Heart 2003;89(4):411–6.
62. Martin BJ, Milligan K. Diuretic-associated hypomagnesemia in the elderly. Arch Intern Med
63. Reyes AJ, Leary WP. Pathogenesis of arrhythmogenic changes due to magnesium depletion. S Afr Med J
64. Reyes AJ, Leary WP. The magnesiuric effects of several single doses of xipamide in healthy adults. Braz J
Med Biol Res 1984;17(3–4):285–91.
65. Brady JA, Rock CL, Horneffer MR. Thiamin status, diuretic medications, and the management of congestive
heart failure. J Am Diet Assoc 1995;95(5):541–4.
66. Granerus AK, Jagenburg R, Svanborg A. Kaliuretic effect of L-dopa treatment in parkinsonian patients. Acta
Med Scand 1977;201(4):291–7.
67. Pinto J, Huang YP, Rivlin RS. Mechanisms underlying the differential effects of ethanol on the bioavailability
of riboflavin and flavin adenine dinucleotide. J Clin Invest 1987;79(5):1343–8.
68. Desouza C, Keebler M, McNamara DB, Fonseca V. Drugs affecting homocysteine metabolism: Impact on
cardiovascular risk. Drugs 2002;62(4):605–16.
69. Childs PA, Rodin I, Martin NJ, et al. Effect of fluoxetine on melatonin in patients with seasonal affective
disorder and matched controls. Br J Psychiatry 1995;166(2):196–8.
70. Strachan J, Shepherd J. Hyponatraemia associated with the use of selective serotonin re-uptake inhibitors.
Aust N Z J Psychiatry 1998;32(2):295–8.
71. Mydlik M, Derzsiova K, Zemberova E. Influence of water and sodium diuresis and furosemide on urinary
excretion of vitamin B(6), oxalic acid and vitamin C in chronic renal failure. Miner Electrolyte Metab
72. Shetty AK, Rogers NL, Mannick EE, Aviles DH. Syndrome of hypokalemic metabolic alkalosis and
hypomagnesemia associated with gentamicin therapy: Case reports. Clin Pediatr (Phila) 2000;39(9):529–33.
73. Aarskog D, Aksnes L, Markestad T, Ulstein M, Sagen N. Heparin-induced inhibition of 1,25-
dihydroxyvitamin D formation. Am J Obstet Gynecol 1984;148(8):1141–2.
74. Aymard JP, Aymard B, Netter P, Bannwarth B, Trechot P, Streiff F. Haematological adverse effects of
histamine H2-receptor antagonists. J Med Toxicol Adverse Drug Exp 1988;3(6):430–48.
75. Vidrio H. Interaction with pyridoxal as a possible mechanism of hydralazine hypotension. J Cardiovasc
Pharmacol 1990;15(1):150–56.
76. Reyes AJ, Leary WP, Van der Byl K. Urinary magnesium output after a single dose of indapamide in healthy
adults. S Afr Med J 1983;64(21):820–22.
77. Ganchev T, Negrev N, Mileva V. Effects of indomethacin on erythropoiesis and plasma iron in rats. Acta
Physiol Pharmacol Bulg 1989;15(2):53–7.
78. Fleming BJ, Genuth SM, Gould AB, Kamionkowski MD. Laxative-induced hypokalemia, sodium depletion
and hyperreninemia. Effects of potassium and sodium replacement on the renin–angiotensin–aldosterone
system. Ann Intern Med 1975;83(1):60–62.
79. Mercado R, Michelis MF. Severe sodium depletion syndrome during lithium carbonate therapy. Arch Intern
Med 1977;137(12):1731–3.
80. Burnier M, Rutschmann B, Nussberger J, et al. Salt-dependent renal effects of an angiotensin II antagonist in
healthy subjects. Hypertension 1993;22(3):339–47.
81. Folkers K, Langsjoen P, Willis R, Richardson P, Xia L-J, Ye C-Q, Tamagawa H. Lovastatin decreases
coenzyme Q levels in humans. Proc Natl Acad Sci USA 1990;87:8931–4.
82. Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment
with HMG-CoA reductase inhibitors. Mol Aspects Med 1997;18(Suppl):S137–44.
Drugs as anti-nutrients 163
Downloaded By: [Moss, Margaret] At: 23:47 1 July 2008
83. Baggott JE, Morgan SL, Ha TS, Alarcon GS, Koopman WJ, Krumdieck CL. Antifolates in rheumatoid
arthritis: A hypothetical mechanism of action. Clin Exp Rheumatol 1993;11(Suppl 8):S101–105.
84. Clark JH, Russell GJ, Fitzgerald JF, Nagamori KE. Serum beta-carotene, retinol, and alpha-tocopherol levels
during mineral oil therapy for constipation. Am J Dis Child 1987;141(11):1210–12.
85. Koblin DD, Tomerson BW, Waldman FM, Lampe GH, Waulk LZ, Eger El 2nd. Effect of nitrous oxide on
folate and vitamin B12 metabolism in patients. Anesth Analg 1990;71(6):610–17.
86. Flippo TS, Holder WD Jr. Neurologic degeneration associated with nitrous oxide anesthesia in patients with
vitamin B12 deficiency. Arch Surg 1993;128(12):1391–5.
87. Ermens AA, Refsum H, Rupreht J, et al. Monitoring cobalamin inactivation during nitrous oxide anesthesia
by determination of homocysteine and folate in plasma and urine. Clin Pharmacol Ther 1991;49(4):385–93.
88. Baggott JE, Morgan SL, Ha T, Vaughn WH, Hine RJ. Inhibition of folate-dependant enzymes by non-
steroidal anti-inflammatory drugs. Biochem J 1992;282(1):197–202.
89. Bjarnason I, Macpherson AJ. Intestinal toxicity of non-steroidal anti-inflammatory drugs. Pharmacol Ther
90. Tang G, Serfaty-Lacrosniere C, Camilo ME, Russell RM. Gastric acidity influences the blood response to a
beta carotene dose in humans. Am J Clin Nutr 1996;64(4):622–6.
91. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin
(vitamin B12). Ann Intern Med 1994;120(3):211–15.
92. Blum M, Kitai E, Ariel Y, Schnierer M, Bograd H. Harefuah 1991;121(10):363–4.
93. Girdwood RH. Drug-induced anaemias. Drugs 1976;11(5):394–404.
94. Masse PG, van den Berg H, Duguay C, Beaulieu G, Simard JM. Early effect of a low dose (30 micrograms)
ethinyl estradiol-containing Triphasil on vitamin B6 status. A follow-up study on six menstrual cycles. Int J
Vitam Nutr Res 1996;66(1):46–54.
95. Melia AT, Koss-Twardy SG, Zhi J. The effect of orlistat, an inhibitor of dietary fat absorption, on the
absorption of vitamins A and E in healthy volunteers. J Clin Pharmacol 1996;36(7):647–53.
96. Russell RM, Dutta SK, Oaks EV, Rosenberg IH, Giovetti AC. Impairment of folic acid absorption by oral
pancreatic extracts. Dig Dis Sci 1980;25(5):369–73.
97. Reicks M, Calvert RJ, Hathcock JN. Effects of prolonged acetaminophen ingestion and dietary methionine
on mouse liver glutathione. Drug Nutr Interact 1988;5(4):351–63.
98. Jones AF, Harvey JM, Vale JA. Hypophosphataemia and phosphaturia in paracetamol poisoning. Lancet
99. Seelig MS. Auto-immune complications of D-penicillamine—a possible result of zinc and magnesium
depletion and of pyridoxine inactivation. J Am Coll Nutr 1982;1(2):207–14.
100. Heller CA, Friedman PA. Pyridoxine deficiency and peripheral neuropathy associated with long-term
phenelzine therapy. Am J Med 1983;75(5):887–8.
101. Seligmann H, Potasman I, Weller B, Schwartz M, Prokocimer M. Phenytoin–folic acid interaction: A lesson
to be learned. Clin Neuropharmacol 1999;22(5):268–72.
102. Hanaki Y, Sugiyama S, Ozawa T, Ohno M. Coenzyme Q10 and coronary artery disease. Clin Invest
1993;71(8 Suppl):S112–5.
103. Lems WF, Van Veen GJ, Gerrits MI, et al. Effect of low dose prednisone (with calcium and calcitriol
supplementation) on calcium and bone metabolism in healthy volunteers. Br J Rheumatol
104. Bouman WP, Pinner G, Johnson H. Incidence of selective serotonin reuptake inhibitor (SSRI) induced
hyponatraemia due to the syndrome of inappropriate antidiuretic hormone (SIADH) secretion in the elderly.
Int J Geriatr Psychiatry 1998;13(1):12–15.
105. Jula A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Ro¨nnemaa T. Effects of diet and simvastatin on
serum lipids, insulin, and antioxidants in hypercholesterolemic men: A randomised controlled trial. JAMA
106. Moosmann B, Behl C. Selenoprotein synthesis and side-effects of statins. Lancet 2004;363(9412):892–4.
107. Baum CL, Selhub J, Rosenberg IH. Antifolate actions of sulfasalazine on intact lymphocytes. J Lab Clin Med
108. Shimizu T, Maeda S, Arakawa H, Mochizuki H, Tokuyama K, Morikawa A. Relation between theophylline
and circulating vitamin levels in children with asthma. Pharmacology 1996;53(6):384–9.
109. Delport R, Ubbink JB, Serfontein WJ, Becker PJ, Walters L. Vitamin B6 nutritional status in asthma: The
effect of theophylline therapy on plasma pyridoxal-59-phosphate and pyridoxal levels. Int J Vitam Nutr Res
110. Slayton W, Anstine D, Lakhdir F, Sleasman J, Neiberger R. Tetany in a child with AIDS receiving
intravenous tobramycin. South Med J 1996;89(11):1108–10.
164 M. Moss
Downloaded By: [Moss, Margaret] At: 23:47 1 July 2008
111. Opala G, Winter S, Vance C, Vance H, Hutchison HT, Linn LS. The effect of valproic acid on plasma
carnitine levels. Am J Dis Child 1991;145(9):999–1001.
112. Kendler BS. Carnitine: An overview of its role in preventive medicine. Prev Med 1986;15(4):373–90.
113. Johnson S. The multifaceted and widespread pathology of magnesium deficiency. Med Hypotheses
114. Rylander R, Arnaud MJ. Mineral water intake reduces blood pressure among subjects with low urinary
magnesium and calcium levels. BMC Public Health 2004;4(1):56.
115. Yokota K, Kato M, Lister F, et al. Clinical efficacy of magnesium supplementation in patients with type 2
diabetes. J Am Coll Nutr 2004;23(5):506S–509S.
116. Gums JG. Magnesium in cardiovascular and other disorders. Am J Health Syst Pharm
117. Maier JA, Malpuech-Brugere C, Zimowska W, Rayssiguier Y, Mazur A. Low magnesium promotes
endothelial cell dysfunction: Implications for atherosclerosis, inflammation and thrombosis. Biochim
Biophys Acta 2004;1689(1):13–21.
118. Touyz RM. Magnesium in clinical medicine. Front Biosci 2004;9:1278–93.
119. Touyz RM. Role of magnesium in the pathogenesis of hypertension. Mol Aspects Med 2003;24(1–
120. Carlin Schooley M, Franz KB. Magnesium deficiency during pregnancy in rats increases systolic blood
pressure and plasma nitrite. Am J Hypertens 2002;15(12):1081–6.
121. Touyz RM, Pu Q, He G, et al. Effects of low dietary magnesium intake on development of hypertension in
stroke-prone spontaneously hypertensive rats: role of reactive oxygen species. J Hypertens
122. Chakraborti S, Chakraborti T, Mandal M, Mandal A, Das S, Ghosh S. Protective role of magnesium in
cardiovascular diseases: A review. Mol cell Biochem 2002;238(1–2):163–79.
123. Walti MK, Zimmermann MB, Spinas GA, Jacob S, Hurrell RF. Dietary magnesium intake in type 2
diabetes. Eur J Clin Nutr 2002;56(5):409–14.
124. Innerarity S. Hypomagnesemia in acute and chronic illness. Crit Care Nurs Q 2000;23(2):1–19.
125. Fox C, Ramsoomair D, Carter C. Magnesium: Its proven and potential clinical significance. South Med J
126. Seelig MS. Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis
treatment. Magnes Res 1990;3(3):197–215.
127. Rosenfeldt F, Miller F, Nagley P, et al. Response of the senescent heart to stress: Clinical therapeutic
strategies and quest for mitochondrial predictors of biological age. Ann N Y Acad Sci 2004;1019:78–84.
128. Lee CK, Pugh TD, Klopp RG, et al. The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction
on life span and gene expression patterns in mice. Free Radic Biol Med 2004;36(8):1043–57.
129. Chung MK. Vitamins, supplements, herbal medicines, and arrhythmias. Cardiol Rev 2004;12(2):73–84.
130. Rosenfeldt F, Hilton D, Pepe S, Krum H. Systematic review of effect of coenzyme Q10 in physical exercise,
hypertension and heart failure. Biofactors 2003;18(1–4):91–100.
131. Mortensen SA. Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design
and end-points of ‘Q-symbio’—A multinational trial. Biofactors 2003;18(1–4):79–89.
132. Berman M, Erman A, Ben-Gal T, et al. Coenzyme Q10 in patients with end-stage heart failure awaiting
cardiac transplantation: a randomised, placebo-controlled study. Clin Cardiol 2004;27(5):295–9.
133. Naini A, Lewis VJ, Hirano M, DiMauro S. Primary coenzyme Q10 deficiency and the brain. Biofactors
134. Singh RB, Kartik C, Otsuka K, Pella D, Pella J. Brain–heart connection and the risk of heart attack. Biomed
Pharmacother 2002;56 (Suppl 2):257s–265s.
135. Rosenfeldt F, Marasco S, Lyon W et al. Coenzyme Q10 therapy before cardiac surgery improves
mitochondrial function and in vitro contractility of myocardial tissue. J Thorac Cardiovasc Surg
136. Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated
depletion of coenzyme Q10. A review of animal and human publications. Biofactors 2003;18(1–4):101–11.
137. Kurowska EM, Dresser G, Deutsch L, Bassoo E, Freeman DJ. Relative bioavailability and antioxidant
potential of two coenzyme q10 preparations. Ann Nutr Metab 2003;47(1):16–21.
138. Colaco CALS (ed.). The Glycation Hypothesis of Atherosclerosis. Austin, Texas: Chapman & Hall, 1997.
139. Leonarduzzi G, Sottero B, Verde V, Poli G. Oxidized products of cholesterol: Toxic effects. In: Preedy VR,
Watson RR, editors. Reviews in Food and Nutrition Toxicity, Volume 3. Boca Raton, Florida: CRC Press,
Drugs as anti-nutrients 165
Downloaded By: [Moss, Margaret] At: 23:47 1 July 2008
140. Aronov DM, Keenan JM, Akhmedzhanov NM, Perova NV, Oganov RY, Kiseleva NY. Clinical trial of wax-
matrix sustained-release niacin in a Russian population with hypercholesterolemia. Arch Fam Med
141. Press RI, Geller J, Evans GW. The effect of chromium picolinate on serum cholesterol and apolipoprotein
fractions in human subjects. West J Med 1990;152(1):41–5.
142. Rosanoff A, Seelig MS. Comparison of mechanism and functional effects of magnesium and statin
pharmaceuticals. J Am Coll Nutr 2004;23(5):501S–505S.
143. Diaz M, Lopez F, Hernandez F, Urbina JA. L-Carnitine effects on chemical composition of plasma
lipoproteins of rabbits fed with normal and high cholesterol diets. Lipids 2000;35(6):627–32.
144. Brook JG, Linn S, Aviram M. Dietary soya lecithin decreases plasma triglyceride levels and inhibits collagen-
and ADP-induced platelet aggregation. Biochem Med Metab Biol 1986;35(1):31–9.
145. Salway JG. Metabolism at a Glance. Oxford: Blackwell Science, 1994.
146. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W.H. Freeman and Co, 2002.
p 518.
147. Moss M, Waring RH. The plasma cysteine/sulphate ratio: A possible clinical biomarker. J Nut Env Med
148. Abraham GE, Rumley RE. Role of nutrition in managing the premenstrual tension syndromes. J Reprod
Med 1987;32(6):405–22.
149. Linder MC. Nutrition and metabolism of vitamins. In: Linder MC, editor. Nutritional Biochemistry and
Metabolism with Clinical Applications. 2nd edition. East Norwalk, Connecticut: Prentice-Hall
International, 1991. p 129.
150. Sheth RD, Stafstrom CE, Hsu D. Nonpharmacological treatment options for epilepsy. Semin Pediatr Neurol
151. Topcu I, Yentur EA, Kefi A, Ekici NZ, Sakarya M. Seizures, metabolic acidosis and coma resulting from
acute isoniazid intoxication. Anaesth Intensive Care 2005;33(4):518–20.
152. Ramachandrannair R, Parameswaran M. Prevalence of pyridoxine dependent seizures in South Indian
children with early onset intractable epilepsy: A hospital based prospective study. Eur J Paediatr Neurol
153. Michae¨lsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med
154. Seelig MS, Berger AR, Spielholz N. Latent tetany and anxiety, marginal magnesium deficit, and
normocalcemia. Dis Nerv Syst 1975;36(8):461–5.
155. Rosanoff A. Magnesium and hypertension. Clin Calcium 2005;15(2):255–60.
156. Rude RK, Gruber HE. Magnesium deficiency and osteoporosis: animal and human observations. J Nutr
Biochem 2004;15:710–716.
157. Matsuzaki H. Prevention of osteoporosis by foods and dietary supplements. Magnesium and bone
metabolism. Clin Calcium 2006;16(10):59–64.
158. Lucas D. Dietary Alcohol and xenobiotics. In: Preedy VR, Watson RR, editors. Reviews in Food and
Nutrition Toxicity, Volume 1. London: Taylor and Francis, 2003, pp 284–304.
159. Carpenter TO, Pettifor JM, Russell RM, et al. Severe hypervitaminosis A in siblings: Evidence of variable
tolerance to retinol intake. J Pediatr 1987;111(4):507–12.
160. Seelig MS, Alba A, Berger AR, Rudez A, Tarlau M. Pilot study of D-penicillamine, vitamins and minerals in
multiple sclerosis. J Clin Psychiatry 1978;39(2):1702–4.
166 M. Moss
... Table 4 provides a brief overview of some commonly prescribed medications and the deficiencies that are potentially associated with these agents. [261] IIIi Other Emerging Mechanisms of Pathophysiological harm ...
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Background: Recent evidence highlights the reality of unprecedented human exposure to toxic chemical agents found throughout our environment - in our food and water supply, in the air we breathe, in the products we apply to our skin, in the medical and dental materials placed into our bodies, and even within the confines of the womb. With biomonitoring confirming the widespread bioaccumulation of myriad toxicants among population groups, expanding research continues to explore the pathobiological impact of these agents on human metabolism. Methods: This review was prepared by assessing available medical and scientific literature from Medline as well as by reviewing several books, toxicology journals, government publications, and conference proceedings. The format of a traditional integrated review was chosen. Results: Toxicant exposure and accrual has been linked to numerous biochemical and pathophysiological mechanisms of harm. Some toxicants effect metabolic disruption via multiple mechanisms. Conclusions: As a primary causative determinant of chronic disease, toxicant exposures induce metabolic disruption in myriad ways, which consequently result in varied clinical manifestations, which are then categorized by health providers into innumerable diagnoses. Chemical disruption of human metabolism has become an etiological determinant of much illness throughout the lifecycle, from neurodevelopmental abnormalities in-utero to dementia in the elderly.
... 12,20,21 Several drugs act as antinutrients, by causing deficiency in essential substances, or by interfering with their functions. 22 In particular, the patients with ESRD are frequently prescribed several medications as well as multivitamins and minerals supplement. The multiple drug uses increase the risk for drug-nutrient interactions in these patients. ...
Patients with chronic kidney disease (CKD) or end-stage renal disease are at risk for vitamin C deficiency and scurvy due to diet restriction, increased urinary loss of the water-soluble vitamin C with diuretics, and in case of patients who are on dialysis, through dialysates. The condition may be overlooked as the clinical manifestation of scurvy may be subtle, and some presentations may mimic clinical signs in CKD. We reported a case of scurvy presenting with gingival bleeding and blood dialysate in a 6-year-old girl with end-stage renal disease who was on continuous ambulatory peritoneal dialysis. Physical examination showed gingival hyperplasia and bleeding, and the pathognomonic bleeding of perifollicular hemorrhage. The typical radiographic changes were present. The clinical signs and symptoms resolved after ascorbic acid treatment. This case underscores the importance of awareness of the increased risk for vitamin C deficiency in patients with CKD and receiving dialysis.
... The title was "Drugs as Anti-Nutrients." 5 The author went meticulously through so many commonly used medications, and for every commonly used medication, there were nutrient depletions that were caused directly by the drug. ...
... only one drug in a group, and we can only suspect that others have the same effect. Some individuals are more susceptible to loss of nutrients than others, and they are more likely to suffer from side effects [Moss 2007]. ...
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Although it is well known and identifi ed that drug-drug interactions exist, the recognition of importance of food and drug interactions to practice has been growing much slower. On the other hand, drug-food/nutrient interactions continue to grow with the common use of medications. Beside the awareness of this type of interactions, food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. Drug-food interactions take place mechanistically due to altered intestinal transport and metabolism, or systemic distribution, metabolism and excretion. In addition, some people have greater risk of food and drug interactions who have a poor diet, have serious health problems, childrens and pregnant women. In this article, basic informations about importance, classifi cations, transporters and enzymes of drug and nutrient interaction are given and some specifi c examples of both drug and nutrients and infl uences on each other are included.
The hair follicle is subject to a constant turnover in the course of perpetual cycles through phases of proliferation, involution, and resting, with regeneration in the successive hair cycle. Understanding the basics of the hair cycle enables insight into the principles of hair growth and shedding. Many factors can lead to a pathologically increased hair loss. Whatever the cause, the follicle tends to behave in a similar way. To grasp the meaning of this generalization requires understanding the varied derangements of the normal hair cycle. Cyclic hair growth activity occurs in a random mosaic pattern with each follicle possessing its own individual control mechanism over the evolution and triggering of the successive phases, including the local milieu at the level of the stem cells. In addition, a number of systemic and environmental factors may have influence, such as hormones, cytokines and growth factors, toxins, and deficiencies of nutrients, vitamins, and energy (calories). Normal supply, uptake, and transport of proteins, calories, trace elements, and vitamins are of fundamental importance in tissues with a high biosynthetic activity such as in the course of hair cycling. It may appear that on a typical Western diet, people are not subject to nutritional deficiencies. Nevertheless, genetic diversity in nutrient requirements, inappropriate food selection or preparation, intensive physical exertion, comorbidities, and use of drugs may lead to deficiency symptoms resulting in unhealthy hair. In fact, nutritional needs fluctuate with age and with situations that occur throughout the life cycle: infancy, childhood, adolescence, pregnancy, lactation, old age, lifestyle (restricted diets, smoking, alcohol consumption), and health status (chronic disease, medications).
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Emerging research suggests that much pediatric affliction has origins in the vulnerable phase of fetal development. Prenatal factors including deficiency of various nutrients and exposure to assorted toxicants are major etiological determinants of myriad obstetrical complications, pediatric chronic diseases, and perhaps some genetic mutations. With recent recognition that modifiable environmental determinants, rather than genetic predestination, are the etiological source of most chronic illness, modification of environmental factors prior to conception offers the possibility of precluding various mental and physical health conditions. Environmental and lifestyle modification through informed patient choice is possible but evidence confirms that, with little to no training in clinical nutrition, toxicology, or environmental exposures, most clinicians are ill-equipped to counsel patients about this important area. With the totality of available scientific evidence that now exists on the potential to modify disease-causing gestational determinants, failure to take necessary precautionary action may render members of the medical community collectively and individually culpable for preventable illness in children. We advocate for environmental health education of maternity health professionals and the widespread adoption and implementation of preconception care. This will necessitate the translation of emerging knowledge from recent research literature, to health professionals, to reproductive-aged women, and to society at large. " The first 38 weeks of life spent in the allegedly protected environment of the amniotic sac are medically more eventful and more fraught with danger than the next 38 years in the life span of most human individuals "
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Although mainstream psychiatric drugs (MPDs) can help to quickly stabilize patients having mental breakdowns or suicidal crises, there are rational reasons for clinicians to consider orthomolecular psychiatric treatment (OPT). The practice of orthomolecular medicine encourages clinicians to diagnose accurately and recommend safer and more effective treatments than MPDs for the following reasons: (1) OPT utilizes substances that are normally present in the human body whereas MPDs are xenobiotics and not normally present in the human body; (2) OPT supports and nourishes the brain and body opposed to MPDs that induce abnormal brain states and can produce worrisome, problematic, toxic and sometimes even disabling psychological and somatic side effects; and (3) OPT is not associated with physiological dependence, withdrawal symptoms, or significant long-term harm whereas MPDs are. Even if there are questions about the author's interpretation of published data or his personal biases, we should still be concerned and re-evaluate the current practice of placing vulnerable patients on MPDs for long periods of time. We need a mental health system that is life-affirming, not life-impeding, and sufficiently open-minded and conscientious to consider seriously the recognized merits of OPT.
Experimental studies, epidemiological surveys, and clinical trials consistently show dietary cholesterol to have a significant effect on plasma cholesterol levels. Increased plasma cholesterol levels are in turn known to promote atherosclerosis and stimulate its progression. Increasing experimental evidence points to cholesterol oxidation products (oxysterols) as being actually responsible for the proatherogenic action of cholesterol, which per se is rather an unreactive molecule. In particular, specific oxysterols of pathophysiological significance exercise strong proapoptotic and proinflammatory action. The most recent findings on oxysterols' toxic and proatherosclerotic effects are described in this chapter. To ensure a comprehensive approach to their potential contribution to the atherosclerosis process, the occurrence of cholesterol oxidation products in foodstuffs, methods for their identification and measurement, and the use of antioxidants supplementation to prevent their generation in foods are reviewed analytically.
Although drug-nutrient interactions can produce therapeutic failure, adverse drug reactions, and altered nutritional status, many clinicians do not recognize this potential when prescribing drugs or understand that drug-nutrient interactions can be as important as drug-drug interactions. In Handbook of Drug-Nutrient Interactions, well-recognized and respected authorities comprehensively review many of the more common, and some less common, drug-nutrient interactions, detailing the mechanisms and clinical approaches to their effective management. Providing more than a simple listing of common interactions, this much needed work explores, in-depth, every major aspect of the problem, including drug and nutrient disposition, enzyme systems, the effects of nutritional status on drug disposition, and the influence of food, nutrients, and non-nutrient components on drug effects and disposition. The authors present the latest findings on the influence of medications on nutrient status and on those interactions relevant to life-cycle stages and to specific patient groups. Separate chapters examine the effects of caffeine, charcoal broiling, grapefruit juice, alcohol, garlic, ginko biloba, dietary minerals, folate, vitamins D and K, and calcium. Cutting-edge reviews offer detailed information on the major drugs affecting the cardiovascular and nervous systems, with emphasis on the antiepileptics. Extensive tables provide clinical recommendations and organize the data clearly to help the reader evaluate nutrition's critical role in optimizing drug efficacy, especially in at-risk populations. An extensive index and copious up-to-date references ensure rapid access to needed information and key citations. Comprehensive and clinically oriented, Handbook of Drug-Nutrient Interactions provides health professionals in many areas of research and practice with the most up-to-date, well-referenced, and easy-to-understand survey of nutrition's central importance in optimizing drug efficacy and avoiding adverse effects. It constitutes a benchmark in the field and should be on the desk of every prescribing healthcare professional as a key reference.
Some genera of lactic acid bacteria and bifidobacteria are the main subjects of this review because they are most commonly incorporated in probiotic products. Since these bacteria are also indigenous to the colon, a strategy for increasing their numbers and/or activity is the use of prebiotics, non-digestible oligosaccharides, that stimulate autochthonous and allochthonous (probiotic) bacteria. At the same time, the potential for using probiotics and prebiotics in combination was recognised and the term synbiotic was proposed for products containing both supplements.
Urinary excretion of vitamin B6, oxalic acid and vitamin C was investigated in 15 healthy subjects during maximal water diuresis and in the group of 12 patients in polyuric stage of chronic renal failure without dialysis treatment receiving a diet containing high sodium chloride (15g/day). Urinary excretions of the same parameters were investigated in another group of 15 patients in polyuric stage of chronic renal failure without dialysis treatment after i.v. administration of 20 mg furosemide. Urinary excretion of vitamin B6, oxalic acid and vitamin C significantly increased during maximal water diuresis while during high intake of sodium chloride the urinary excretions of these substances were not affected. The results suggest that urinary excretion of vitamin B6, oxalic acid and vitamin C depends on the urinary excretion of water. Intravenous administration of 20 mg furosemide led to an increase of urinary excretion of vitamin B6, oxalic acid and vitamin C in patients with chronic renal failure. The increased urinary excretion of vitamin B6 and vitamin C is a new negative side effect of furosemide and increased urinary excretion of oxalic acid is a new positive side effect in patients with chronic renal failure.