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Abstract

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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Journal of Nutritional &
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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
3NP
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
URL: http://dx.doi.org/10.1080/13590840701352740
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Downloaded By: [Moss, Margaret] At: 23:47 1 July 2008
REVIEW PAPER
Drugs as anti-nutrients
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
Abstract
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.
Key words: drug–nutrient interaction, drug–vitamin interaction, drug–mineral interaction, nutrient
deficiency, vitamin deficiency, mineral deficiency, coenzyme Q10 deficiency
Introduction
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.
Results
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.
Discussion
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
2
-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
antagonist)
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 –
antibiotic)
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
phenytoin.
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
subject.
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
sweating.
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
exercise.
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
antibiotics.
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.
Conclusion
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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Acknowledgement
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.
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