Crucial New Insights Into the Metabolism of Medications
When we examine the interactions of medicines with the body, we are interested in what the medicine does to the body, and also what the body does to the medicine: what we call pharmacokinetics and pharmacodynamics. But it has long been known that these two essential considerations are far from being the whole story: there are enormous differences in the ways in which people respond to medicines: some people need huge doses of a medicine, whilst there are others who cannot tolerate medicines at all. Though part of the explanation for those differences is clearly not just pharmacological – the same people who are super-sensitive to medicines are often also extraordinarily sensitive to acupuncture and homeopathy – there is a new kid on the block: a new factor in drug metabolism.
Men and women handle medicine differently, the time of day that a medicine is taken, as well as things like the food eaten in the last few hours can all impact the outcomes of taking a medicine. We have also known that there are many other variables in a person’s response to a medicine.
For more than two decades physicians and pharmacologists have wondered if the three pounds of bacteria living peacefully in our intestines might have a major impact on the metabolism of medicines. This question was first prompted by clinical observations: first, people with no intestinal bugs exhibited many oddities in how they handled medicine, and second, there are some rare situations in which overgrowth with unusual bacteria can chew up certain essential nutrients.
New research reported by the BBC confirms these clinical observations.
Researchers at Imperial College London and the pharmaceutical giant Pfizer have used a “pharmaco-metabonomic” approach that uses a combination of advanced chemical analysis and mathematical modeling to predict responses to drugs. Details of the research are published in the journal Nature.
The method is based on an analysis of the chemical products of the body’s metabolism. We think that examining these patterns can help diagnose diseases, predict an individual’s future illnesses, and their response to treatment.
The principle investigator is Professor Jeremy Nicholson and he has said the ‘pharmaco-metabonomic’ approach appears able to take account of individual differences in the way that drugs are absorbed and processed by the body. It differs from person to person depending on factors including the type and amount of bacteria found in the intestines.
These new techniques could be the first step towards the development of more personalized pharmacological treatments. For those of us practicing integrated medicine, this is a most welcome development.
Technorati tags: drug metabolism gender differences intestinal bacteria pharmacodynamicspharmacokinetics
Glucosamine and Chondroitin
A study has been published in last week’s New England Journal of Medicine that seems to show that there’s no advantage in taking the popular dietary supplements glucosamine and chondroitin. Indeed that’s what has been reported in the media . But notice that I said, “Seems to show,” for on closer examination there is more to this paper than it appears.
The investigators are to be congratulated for doing the study in the first place. What they did was to take a large group of 1583 patients who all had osteoarthritis of the knees, and divide them into five groups:
- A placebo group
- A group that took celecoxib (Celebrex) 200mg/day
- 1500mg of glucosamine/day
- 1200mg of chondroitin/day
- A combination of 1500mg of glucosamine/day and 1200mg of chondroitin/day
The study lasted 24 weeks, and the main outcome measure was pain in the knees. The study showed that although patients on Celebrex did very well compared with the placebo group, those on glucosamine and chondroitin did not do better than placebo, although the combination was better than using either supplement alone. But one of the odd things was that people with moderate to severe pain WERE helped by the combination, and in fact the combination out-performed Celebrex!
Not only does the combination seem to help people with the biggest problems with pain, but also there are some other important points:
1. The worse someone is, the bigger the room for improvement. If someone only has mild pain, you need a lot more patients to find a statistically significant improvement.
2. As in most studies, multiple measurements were done, and Celebrex was no better than placebo in 12 out of 14 of them. So if the “active comparison” failed on multiple measures, we need to be very cautious about how we interpret the study.
3. The placebo response rate in the study was 60%, while the average is 30-35%. This is a huge difference. This may be because the patients knew that they had a four in five chance of getting a treatment that might help them, so they went into the study with high expectations.
4. This is only one study, concerning one type of joint problem. There are more than 30 others that have in general been even more positive then the findings in the moderate to sever group, including a very long-term study that showed that over an eight-year period, the combination dropped the rate of knee replacement by almost 75%. It is crucially important to examine the results of any study in the context of everything else that has been known and discovered. Every type of study has to be checked, and verified.
5. The study was funded by the National Institutes of Health and is the first of two parts, with a second study of the impact of the treatments on X-rays of the knees still pending.
6. None of the groups had many side effects, but it is worth remembering that medicines of the Celebrex type are under intense scrutiny because of the possible association with cardiovascular disease.
7. Many specialists use anti-inflammatory medicines together with glucosamine/chondroitin, at least at the beginning of a course of treatment. And that makes good sense.
8. What about the dosing of the supplements? Although those are the doses used by most people, they may not always be enough. In patients who weigh more than 200 pounds, many experts recommend 2000mg of glucosamine and 1600mg of chondroitin. It is also wise to take the supplement in divided doses with food. (I have sometimes also found it very useful to add Methylsulfonylmethane (MSM), 1000mg/day to the glucosamine and chondroitin, though there is little research to support it.)
None of these treatments can be given to pregnant women or nursing mothers.
One other small caveat, if you are having surgery make sure that you tell you surgeon if you are taking these supplements. Chondroitin has minor anticoagulant activity , and so may glucosamine.
And remember that the maintenance of joint health is not just a matter of taking some supplements. It is a judicious mixture of taking the right medication when needed, together with supplements, a healthy diet containing some omega-3 fatty acids and antioxidants, exercise, management of posture, particularly of the spine, and weight management. To say nothing of ensuring that joint problems are not being compounded by psychological and relationship problems, and disturbances in the subtle systems of the body.
Technorati tags: glucosamine, chondroitin, knee pain, arthritis
Brazilian Diet Pill
My colleagues over at the Psychiatric Resource Forum just got this FDA warning and asked me what I thought. I am reproducing in its entirety:
“MedWatch – The FDA Safety Information and Adverse Event Reporting Program The FDA warned consumers not to use two unapproved drug products that are being marketed as dietary supplements for weight loss. Emagrece Sim Dietary Supplement, also known as the Brazilian Diet Pill, and Herbathin Dietary Supplement may contain several active ingredients, including controlled substances, found in prescription drugs that could lead to serious side effects or injury. They contain chlordiazepoxide HCl (the active ingredient in Librium), and fluoxetine HCl (the active ingredient in Prozac). Emagrece Sim and Herbathin were also found to contain Fenproporex, a stimulant that is not approved for marketing in the United States. Consumers are advised not to use the Emagrece Sim and Herbathin products and to return them to the suppliers. There may be other manufacturers or suppliers of imported Emagrece Sim and Herbathin, and consumers should exercise caution in using any of these imported products.
Read the complete MedWatch 2006 Safety summary, by using the following link: FDA news release
My Comments: Sadly this sort of thing is not uncommon. An unknown but clinically significant proportion of the Ayurvedic and Chinese herbs that are imported into the United States and Europe contain steroids and other drugs. I once diagnosed two cases of Cushing’s syndrome that were the result of people taking imported Indian herbs. One of them was an Indian man who was referred for weakness of his proximal muscles, which prevented him from walking up the stairs. He also add other classic symptoms of Cushing’s syndrome: he had gained weight, particularly in the face and around the abdomen, he had high blood pressure and diabetes mellitus. The other had a less florid presentation. There have been quite a number of publications on the subject of adulteration of herbal remedies.
Several years ago I became involved in an investigation of some apparently miraculous cures of eczema with Chinese herbal remedies, and sadly some of these had also been adulterated with corticosteroids. This was a real shame, because some of the herbal remedies actually helped eczema even if they did not contain steroids. These cases are all the more sad, because there are also large numbers of companies that make Indian and Chinese herbs to the highest possible standards, yet the bad apples have put even these under scrutiny.
The message must be that just because something is natural does not guarantee that it is safe. I have said before, but it bears repeating that arsenic, deadly nightshade and hurricanes are all natural. It is essential to obtain any herbals from a reputable source and to ensure that your health care provider knows exactly what you are taking: apart form the topic of adulteration, there are hundreds of potential interactions between herbal and prescription medicines.
Within the last three months, I have written an educational program for professionals that explores these issues in considerable detail, and makes recommendations about reliable suppliers of herbs.
Technorati tags: brazilian diet, diet pills, herbal medicines
