Introduction

In the United States, approximately 1 in 4 persons prescribed pharmaceutical medications also consume a dietary supplement.^{1, 2} Dietary supplements that include herbs, vitamin and/or mineral preparations, and other dietary supplements such as glucosamine and fish oils, may augment or antagonise the actions of prescription and non-prescription drugs. This is because supplements have demonstrated pharmacologic actions that may then go on to produce therapeutic outcomes.³ Moreover, supplements that do not have a documented pharmacologic action can also significantly affect the absorption, metabolism, and disposition of other pharmaceutical products. Health professionals usually question the nutritional adequacy and safety of a patient’s diet, however the nutritional impact of medications is often overlooked. Pharmaceuticals have both beneficial and adverse effects, although there is a strong focus on the benefits. Furthermore, drug–drug interactions are generally integral to decision-making yet the impact of drug–food and drug–nutrient interactions are rarely acknowledged or, mostly, deemed clinically insignificant.

Some vitamin–mineral–herbal supplements require separation from medications by about 2–4 hours to avoid potential problems with absorption or interactions. See the medications in Table 37.1 for more specific advice in relation to this rule.

Table 37.1 Common herbs and nutrients and their interactions with medications

Drugs	Interactions
Central nervous system and sedating medication
Herb	Effect
St John’s wort	SSRIs and any other medication with serotoninergic effect (e.g. tramadol) Warn patients not to initiate St John’s wort when receiving SSRI medication — may cause serotonin syndrome Patients should discuss use of St John’s wort with their GP and their pharmacist

  Avoid with alcohol, benzodiazepines, barbiturates, psychoactive medication, narcotic opioids such as codeine, pethidine and oxycodone, and anti-anxiolytics as may potentiate sedating effect Anticoagulant medications^(a) Nutrient or herb Effects on anticoagulant St John’s wort Reduced serum levels of warfarin and reduces INR. Monitor INR carefully Gingko biloba Does not interact with warfarin and/or aspirin directly. Has anti-platelet activity. Does not significantly affect clotting status of warfarin. In combination with NSAIDS such as aspirin can cause severe bleeding (e.g. intra-cranial haemorrhage) Ginger May affect clotting status and potentiate effect of warfarin Garlic Asian ginseng (Panax ginseng) No effect on warfarin American ginseng (Panax quinquefolius) Decreases serum warfarin levels Siberian ginseng (Eleutherococcus senticosus) Has not been studied, however contains constituents that inhibit platelet aggregation Devil’s claw (Harpagophytum procumbens) Potentiates anticoagulant effects Glucosamine Potentiates warfarin effect and increases INR Fish oils 3–6g daily does not affect coagulation status in patients on warfarin. Caution is still needed due to their anti-platelet effect, especially at higher doses and stop use 2 weeks before surgery Vitamin E Enhances anti-platelet effect of aspirin. No clear increased risk of bleeding in patients on warfarin Cranberry juice, Seville oranges, pomegranate juice Papaya May increase INR Red clover (Trifolium pratense) Due to its coumarin content, red clover may increase the risk of bleeding. Avoid use with warfarin and 2 weeks prior to surgery Saw palmetto (Serenoa repens) May increase risk of bleeding. Avoid use with warfarin and 2 weeks prior to surgery Cardiovascular medications^(b) Herb Effect St John’s wort^(c) Decreases serum levels of verapamil, statins and digoxin Ginseng^(c) Increases digoxin levels Licorice Increases urinary excretion of potassium and reduces serum potassium. Can increase blood pressure. Avoid with antihypertensive medication, potassium depleting medication such as thiazide diuretics, corticosteroids such as prednisolone, corticosteroid inhalants and cortisol, digoxin Hawthorn May interact adversely with Digoxin. May potentiate blood pressure lowering effects, thereby requiring modified drug doses Fibre and gastrointestinal tract (GIT) supplements Supplement Effect Psyllium (dietary fibre)^(d) Slippery elm bark May reduce absorption of any medication as it coats the lining of the GIT Diabetes medications Nutrient and/or herb Effect on diabetes medication Hawthorn No interaction found Chromium, psyllium, ginseng, fenugreek, gymnema, bitter melon All have hypoglycaemic effects in patients with diabetes, which may be unpredictable. No specific changes in hypoglycaemic doses are needed unless blood sugar level changes occur HIV medications Nutrient and/or herb Effect on HIV medication Garlic and vitamin C Reduce serum antiretroviral medications Milk thistle, echinacea species and goldenseal No clinically relevant effect St John’s wort Risk of dangerous interaction. Discourage use of herb Ginkgo Possible drug failure Hormonal medications Nutrient and/or herb Effect on hormonal medication Ginseng Saw palmetto (Serenoa repens) Soy Red clover (Trifolium pratense) Vitex agnus castus May potentiate progesterone effect High dose iodine/kelp/seaweed

(a) All patients on warfarin should be monitored closely with the introduction of any complementary medicine such as garlic, fish oils, ginseng and ginkgo.

(b) Given the serious consequences associated with small changes in the coagulation status, patients on warfarin should be carefully monitored when: 1) initiating or stopping any nutritional or herbal supplement 2) commencing new bottles of the same product in case of product variation.

(c) Monitor serum digoxin levels in patients taking St John’s wort and ginseng.

(d) Separate psyllium by several hours to allow the absorption of drugs to occur more effectively.

Key points regarding herb-nutrient-drug interactions

Examine food habits or metabolic changes carefully in any patient who unexpectedly gains or loses weight while taking drugs.

Grapefruit juice, Seville orange juice and pomegranate juice inhibit cytochrome p450 (CYP450) and 3A4/5 in the liver and gut for up to 72 hours and can therefore increase serum concentration of some drugs (e.g statins, antidepressants, beta blockers, calcium channel blockers, hormone replacement therapy [HRT], warfarin, anticonvulsants, antipsychotics) into toxic ranges.

As a general rule separate vitamin–mineral–herbal supplements from medications by about 2–4 hours as they may increase or decrease each others absorption in the gut and/or affect metabolism, thus increasing risks of toxicity or insufficiency.

Types of herb–drug interactions

There are 2 types of interactions that occur between natural products and pharmaceuticals.

The evidence documenting dietary supplement–drug interactions varies extensively. There is at present no process for the systematic evaluation of dietary/nutritional supplement products for possible interactions with prescription medications. As a result of this deficit, there is an incomplete knowledge of the interactions that may occur. The information is largely researched from many different sources including animal studies, human case reports, case series, historical contraindications, and the extrapolation from basic pharmacology data, or from clinical trials. Many of the recommendations associated with herb–drug interactions are based on speculation rather than research.⁴ According to a recent study, overall the risk of actual harm from a herb–drug interaction is low.⁵ According to the authors the 5 most common natural products with a potential to affect medications include garlic, St John’s wort, ginkgo, valerian and kava. These herbal medicines accounted for 68% of the potential clinically signifi cant interactions in the survey. The 4 most common prescription medicines affected by supplements are antithrombotics, such as warfarin, antidepressants, sedatives and anti-diabetic agents.

Types of nutrient–drug interactions

Pharmaceuticals can affect and be affected by nutrition.

Drugs can also affect many nutritional factors such as appetite, taste acuity and gastrointestinal function. Food habits or metabolic changes should be examined carefully in any patient who unexpectedly gains or loses weight or has altered bowel motions while taking drugs.

As a general rule, it is advisable to separate vitamin and/or mineral supplements from medications by about 2–4 hours to reduce any potential interactions. However, where the drug affects metabolism or excretion of a nutrient such a simple rule may not apply.

Even though a patient’s diet may be supplying a moderate amount of vitamins and/or minerals, they may be tipped into nutritional insufficiency or deficiency due to their medications. If these deficiencies are not corrected through diet (and supplements if indicated) they may further complicate the management of the condition or create new health problems.

Nutrient supplementation may not necessarily be needed in combination with a nutrient-depleting pharmaceutical. Clinical symptoms of nutrient deficiency and/or insufficiency combined with laboratory data are needed to verify changes in nutritional status. A nutrient dense diet, however, makes an important contribution to the health of medicated patients and reduces the risk of nutritional disorders or altered drug efficacy. Health professionals need to be knowledgeable and vigilant of nutrition-related clinical symptoms that may be caused by pharmaceuticals.

Figure 37.1 lists the top 12 nutrient-depleting drugs (see also Appendix 2).^{6, 7}

Patient populations and specific pharmaceuticals