Effects of supplements on medicines 'dangerous'

Herbal remedies such as echinacea and St John’s Wort “could make medication dangerous”, the Daily Mail has warned.

The story is based on a large review of evidence that aimed to identify potentially harmful interactions between supplements (herbal and dietary) and conventional medicines.

These types of supplements are increasingly popular, and include:

St John’s Wort – used in an attempt to improve mood
gingko – used in an attempt to boost energy
echinacea – used in an attempt to strengthen the immune system

The study found that the supplements St John’s Wort, magnesium, calcium, iron and gingko had the greatest number of interactions with conventional drugs. The medicines warfarin, insulin and aspirin had the greatest number of interactions with herbal and dietary supplements.

Warfarin was reported to have more harmful interactions than any other drug. Most adverse events – across all supplements and medicines examined – were “moderately severe” and included abdominal problems, seizures and psychiatric disorders.

The herbal products flaxseed, echinacea (often taken for colds) and yohimbe (popular for libido problems) had the largest number of reported ‘contraindications’. A contraindication is where the products should not be used because they are known to interact with conventional medication or they can worsen a pre-existing health condition.

The UK market for herbal and dietary supplements continues to grow, with many people mistakenly viewing them as “natural” and therefore harmless.

Anyone taking conventional medication is advised to speak to their GP or pharmacist before using a herbal or dietary supplement.

Where did the story come from?

The study was carried out by researchers from China Medical University in Taiwan and the University of Illinois at Chicago in the US, and was funded by the National Science Council, China Medical University Hospital and the Department of Health in Taiwan.

The study was published in the peer-reviewed International Journal of Clinical Practice.

The findings of the study were reported fairly by the Daily Mail and The Daily Telegraph. Both included comments from an independent expert, taken from an accompanying editorial.

What kind of research was this?

This was a review of the literature published between 2000 and 2010 on the drug interactions between herbal remedies and dietary supplements and conventional medicines. It also looked at whether or not contraindications to the use of the supplement were documented.

The authors point out that the use of herbs and dietary supplements has risen dramatically in recent decades, with more than half of all US patients with chronic disease or cancer having used them and nearly one-fifth of patients taking herbs and dietary supplements at the same time as prescribed medications.

The potential risks of combining supplements with medication are still poorly understood by consumers, with many believing supplements are safe despite evidence of side effects, they say. For healthcare professionals, the evidence on interactions between medication and supplements, and on side effects of supplements, is sometimes uncertain and conflicting.

The researchers aimed to give healthcare professionals a resource summarising all the published scientific evidence for interactions between supplements and conventional drugs.

What did the research involve?

The researchers conducted a search of original study publications, including textbooks and online resources, for any evidence relating to drug interactions with, or contraindications for, herbal remedies and dietary supplements, between 2000 and 2010.

Supplements were defined as any product containing one or more of the following ingredients:

a vitamin, such as vitamin A
a mineral, such as zinc or magnesium
a botanical or plant source, such as St John’s Wort
an amino acid, such as glutamine
other types of dietary supplements, such as fish oil

Traditional plant foods were excluded. The articles selected were reviewed independently by two authors who excluded any literature not relating to the topic. There were no restrictions on the type of study included, so that animal studies, clinical trials, observational studies and review articles were all assessed.

The researchers extracted information from the selected articles on interactions between supplements and medicines, and on documented contraindications for taking supplements. In this case, a contraindication primarily means when a supplement should not be used when the patient is taking a particular medicine, because of potential harm. Supplements were grouped into three categories – herbal, vitamin and mineral, and other. Drugs were classified using a standard classification system, according to their mechanism of action.

The researchers also rated interactions for their severity, using two databases, and categorised the mechanism for interactions. From this information they defined the frequency of drug-supplement interactions, the possible mechanisms and their severity ratings.

What were the basic results?

The researchers found 1,491 different interactions between herbal and dietary supplements and medicines. These involved 213 different supplements and 509 medications.

Herbal and dietary supplements containing St John’s Wort, magnesium, calcium, iron and gingko had the greatest number of reported interactions.
The drug warfarin (an anti-clotting drug that ‘thins’ the blood) had by far the largest number of reported interactions with supplements (105). This was followed by insulin (41 reported interactions), aspirin (36), digoxin (32) and ticlopidine (23).
Medications affecting either the central nervous system or the cardiovascular system were those most commonly associated with interactions.
42.3% of the interactions were due to “altered pharmacokinetics” (the supplement interfered with the absorption or action of the medication in the body).
240 (about 16%) were described as major interactions – that is interactions that posed a potentially significant risk to health, such as triggering excessive bleeding.
152 contraindications to supplements were found. The most frequent of these were gastrointestinal (16.4%), neurological (14.5%) and kidney or genitourinary disease (12.5%).
The herbal products flaxseed, echinacea (often taken for colds) and yohimbe (taken for libido problems) had the largest number of reported contraindications
Herbal remedies were reported as having more drug interactions and contraindications than dietary supplements.

How did the researchers interpret the results?

The authors say that although the interactions they found concern relatively small groups of medicines and supplements, it is important that healthcare professionals inform patients about them to prevent harmful events.

In an accompanying editorial, Professor Edzard Ernst, a specialist in complementary medicine at the University of Exeter says that the number of interactions found between supplements and prescribed drugs could be under-reported and just the “tip of the iceberg”.

“Patients deserve reliable information, and it is our duty to provide it”, he says. “We have to become vigilant and finally agree to monitor this sector adequately. Each individual doctor can contribute to this process by routinely including questions about alternative medicine use in their medical history taking”.

Conclusion

This is a useful review that highlights the potential for harmful interactions between conventional medicines and herbal and dietary supplements. Current knowledge in this area is incomplete, and this review of the literature provides a useful summary of the current understanding.

The review did not restrict itself to clinical trials, but covered all types of studies including case reports, books and, potentially, animal studies. Given the uncertainties in this area, this approach is justified. However, it is important to be aware that, as this is only a review of the published literature, other interactions between supplements and conventional medicines may have been observed and gone unpublished.

Of reported interactions, by far the most common were interactions between herbal and dietary supplements and warfarin. This is not surprising. Warfarin is a drug that requires close monitoring, and a large number of conventional medicines are already known to interact with the absorption or breakdown of warfarin in the body – either making it more ineffective (impairing its anti-clotting function) or enhancing its effect (increasing its anti-clotting function and thereby increasing bleeding risk). Therefore, many of the chemicals that may be in supplements may also have these unwanted interactions with warfarin. St John’s Wort is a particularly notable example of a herbal supplement that interacts with warfarin and impairs its anti-clotting function.

There is a growing market for herbal and dietary supplements, which are often available over the counter in supermarkets and pharmacies.

Many people mistakenly view supplements as “natural” and therefore harmless. In fact, herbal remedies should be regarded in the same way as conventional medications. They can have a potentially wide range of effects, some of which can be very unpleasant, and they can interact with both prescription and over-the-counter medications.

Also, not all herbal remedies are safe or suitable for everyone. In particular, they may not be suitable for people with a chronic medical condition (such as kidney disease) or people taking medication, such as warfarin, on a long-term basis.

The most important message is that it is always a good idea to ask your GP or pharmacist for advice before you begin using a herbal or dietary supplement.