Positive Health Online

These days we are all pretty sophisticated about the gap between rhetoric and reality. Our detectors are finely tuned when it comes to sniffing out the hype in adverts or the promises of political parties, but they all-too-often become curiously disconnected when faced with claims about the benefits of drugs. Maybe it’s because drugs offer a quick fix when we are at our most vulnerable that we yearn to believe they are somehow not so tainted with the hucksterism of the marketplace as, say, double-glazing or life insurance.

Profit Motive of the Drug Companies

Although it sounds blindingly obvious, it seems worth pointing out just how much money pharmaceuticals generate and that drug marketing has only a tangential relationship with our health but everything to do with maintaining a healthy balance sheet. The global market for pharmaceuticals was estimated at around $600 billion in 2003, a figure that has certainly grown since then. And where does much of the money come from? From the sale of drugs for chronic diseases; not because they are the ones in greatest need of curing – in fact none of these drugs actually cure anything – but because these are the most profitable.

The twenty-four top-selling drugs are all targeted at treating or preventing just six disorders, each one the kind of chronic condition that responds well to non-drug and nutritional therapies. In 2004, these twenty-four drugs racked up an astonishing $67 billion in global sales between them.[1] Here are the disorders they are designed to treat:

• High cholesterol (4 brands, total worth $20 billion)
• High blood pressure (5 brands, total worth $12.5 billion)
• Heartburn and ulcers (6 brands, total worth $12 billion)
• Depression (4 brands, total worth $10 billion)
• Psychosis (3 brands, total worth $9.4 billion
• Joint pain (2 brands, total worth $4.7 billion).

The power of the profit motive in shaping drug research is nowhere clearer than in the current situation with antibiotics. Drug-resistant bacteria are a growing menace – 5,000 people die from infections by them in UK hospitals alone – so you might think companies would be engaged in a fierce race to come up with a solution. In fact, drug company microbiological research has virtually ground to a halt. Why? Because they just don’t make enough money.

Antibiotics are the drugs that gave rise to the myth of modern medicine’s ability to develop so-called ‘magic bullets’. They are the foundation of the drug industry, and yet between 2000 and 2004 many of the large drug companies actually abandoned antibiotic development and closed their Microbiology departments.[2] As a result, out of 506 new drugs from major firms in the final stages of testing, only six were antibiotics and none of them were aimed at the new targets (that is, proteins or enzymes) thrown up by genetic research.

There is no pretence about the reason behind this trend – the drugs’ inherent unprofitability. As top science journal Nature put it: ‘Antibiotics are the worst sort of pharmaceutical because they cure the disease.’[3] After all, people generally take a course of antibiotics for a week, then stop. Blockbuster drugs that sell billions, the article says, come from developing treatments that people take for a lifetime, say for chronic disorders like high cholesterol or hypertension.

So maybe a degree of scepticism is in order when drug companies defend their high profits by saying they need the money to pay for the life-saving new drugs they are working on. In fact, just as the drugs companies are not interested in antibiotics, they are not really interested in genuinely new drugs either. That’s because it’s far more profitable to concentrate on developing drugs that are almost exactly the same as one you have already but just different enough to win a new patent. The reason is that new patented drugs can be sold for about ten times more that one whose patient has run out, so the aim of the bulk of the research is not innovation but to develop replacement drugs.

That might be fine, if they represented a big improvement on the older ones. But do they? Not according to a recent Canadian study, which found that during the thirteen years between 1990 and 2003, out of 1,147 newly patented drugs classified by the Canadian Patented Medicines Prices Review Board, only 5.9% were considered to be ‘breakthrough drugs’, that is, those providing a ‘substantial improvement over existing drug products.’[4]

And yet according to the same research, spending on prescription drugs in Canada doubled between 1996 and 2003, and 80% of that was accounted for by new drugs ‘that did not offer substantial improvements on less expensive alternatives available before 1990’. And it’s not just Canada that is affected. The report concludes that ‘me-too drugs probably dominate spending trends in most developed countries’.

Drug Companies Control Drug Research

Bringing these drugs to market is made easier by the fact that the drug companies pay for almost every step of the system that is theoretically designed to control them. Drugs have to be tested for safety and efficacy; it’s an almost invisible $14 billion industry in the US, involving 10,000 trials a year.  You might think that testing the drugs should be done by bodies other than the drug companies involved – certainly a recent editorial in the BMJ suggested just that.[5]

In fact, the drug companies don’t just pay the testing centres. They also, remarkably, fund up to 5,000 ‘institutional review boards’ in the US, responsible for ensuring the testing centres follow medical and ethical guidelines. A recent report on this system painted an alarming picture of a setup that is ‘poorly
regulated and riddled with conflicts of interest’.[6]

Of course in theory, even if the controls on testing were lax, you might think that problems and oversights would be picked up by a country’s drug regulatory agency. Bodies like the UK’s MHRA and the FDA in the US are charged with first licensing drugs – reviewing the evidence to make sure that they are safe and effective – and then monitoring what happens to patients once they are being widely used.

But they are almost totally funded by the drug companies as well. Both the American FDA and the UK’s MHRA have has been heavily criticized for their failings by recent reports.

Documents obtained recently via the UK’s Freedom of Information Act showed that the industry privately drew up its own detailed blueprint of how the MHRA should be run, proposing to ‘build on the excellent working relationship between the industry and the regulator’. They also revealed that the industry was ‘agitated about the ministers’ unrealistic plans to tighten the rules on conflicts of interest’.[7]

The sense that drug companies’ interests were the agency’s first priority and patients’ a distant second was reinforced by Richard Brookes, director of the mental health charity Mind, and the first patient’s representative to sit on an MHRA review committee. He declared himself ‘horrified’ to find that the agency had kept quiet about the possible dangers of higher doses of SSRIs for at least a decade. When he resigned, he declared that the MHRA was either guilty of ‘extreme negligence or, worse, dishonesty’.[8]

Despite a regulatory system that would spark outrage if it were discovered that airline safety or environmental health inspections were run in the same way, one of the most powerful myths about modern pharmaceutical treatments is that they have been rigorously tested. The great dividing line between drug-based medicine and non-drug treatments is claimed to be that the efficacy and safety of drugs has a rigorous evidence base.

Off-Label Prescribing

In fact, this is more like a mission statement, a worthy aspiration rather than a description of what actually goes on when drugs are prescribed. Take what’s known as ‘off-label’ prescribing. When a drug gets a license, it is for a particular use – to treat asthma, lower cholesterol – and the drug company has to provided evidence that it does that better than a placebo. Many drugs are prescribed for uses they have not been licensed for and so without that evidence base.

In the summer, the Archives of Internal Medicine published a paper showing that on average, 21%  of the 160 most commonly prescribed drugs in the US were given to people on an off-label basis – i.e. without any proper evidence that they were safe or effective for that condition.[9] This wasn’t a small-scale study either, being based on an analysis of a database that tracks the prescribing habits of a representative 3,700 doctors around the country.

Different specialities had different rates of off-label prescribing. For instance, 46% of heart drugs (except those to lower cholesterol or reduce blood pressures) were prescribed off-label, while in the case of one widely used drug Neurontin (gabapentin), licensed for epilepsy and nerve pain, 98% of its uses were off-label for unrelated conditions such as bipolar disorder and depression.

The really shocking part of the study – conducted at Stanford University – was that for nearly three-quarters of the off-label uses there was ‘little or no scientific support’. Drugs that have been extensively prescribed off-label and then been discovered to cause considerable harm include HRT (cancer and heart disease) and SSRI anti-depressants to children (suicide).

Nutritional Medicine Evidence

Given these acknowledged problems with the drug model – and they are all an open secret within the profession; medical journals write about them regularly – if evidence-based medicine was really being practised, then doctors would at least be looking at the nutritional approach and pushing for it to be far more widely tested and trialled.

After all, it doesn’t require any special or strange mechanisms. In fact, after the drug revolution in the 1960s and 1970s, it became clear that food and supplements directly affect many of the same biochemical pathways in the body that drugs target, but with far fewer side effects. For instance, omega-3 fats lower production of the same inflammatory chemicals that Vioxx does – without damaging the heart. Diet and supplements can lower the blood-sugar levels of diabetics more effectively than drugs, while supplements can raise serotonin levels in the brain as well or better than antidepressant SSRIs.

Yet you are unlikely to hear anything about this at your doctors, because the vast majority know nothing about it. If your doctor qualified more than ten years ago, chances are he or she had fewer than twelve hours of training in nutrition per se. Of course, every doctor will advise patients to eat healthily and take exercise, but with no specialist knowledge, their advice can be too general to effectively target what’s actually, specifically wrong. So they fall back on bald assertions that there is no evidence for the ability of nutrition to treat disease and explain away any successes they encounter in terms of the placebo.

Yet there are hundreds of studies showing nutrition has a direct effect on disease; here’s just one of hundreds. A follow-up study of 84,000 nurses over 16 years – a lot of people over a long time – found that: ‘higher consumption of fish and omega-3 fatty acids is associated with a lower risk of coronary heart disease (CHD) particularly CHD deaths’.[10] And what do all those medics who are so committed to evidence-based medicine say about such research? They simply ignore it.

Diabetes

That’s where you come in. In our book Food is Better Medicine Than Drugs, Patrick Holford and I looked at the evidence for the effectiveness of drugs for the treatment for chronic diseases, and compared with what could be done with nutrition and supplements. The more people who engage with their doctors when following a nutritional approach – rather than understandably giving up on them – the harder it becomes for doctors to ignore it. This is what we found about with just one condition diabetes, one of the fastest-growing disorders in the country that is regularly treated with drugs.

Diabetes drugs are big business. UK sales are worth close to £1 billion a year and rising. They work by affecting different parts of the body’s glucose balancing act – either by making cells more responsive to insulin or by boosting insulin production.

The oldest and most commonly used is one called metformin; it lowers your blood sugar by increasing insulin sensitivity in the muscles and the liver where glucose is stored. It is the best of the bunch but its side-effects include gastro-intestinal symptoms such as mild nausea, cramps and vomiting, and soft or loose stools; a new, slow-release formulation does minimize them.

Unlike the others, it doesn’t make you put on weight; a serious drawback to diabetes drugs you might think, since diabetes is one of the effects overweight people are warned about. It can, however, cause vitamin B12 deficiency,[11] which is likely to allow levels of a damaging amino acid called homocysteine to rise, which in turn increases your risk of a heart attack, unless you supplement.

Even less appealing, unless absolutely unavoidable, is a class of drugs known as Sulfonylureas, which stimulate the beta cells in the pancreas to produce more insulin. But most Type 2 diabetics produce too much insulin already – their problem is not lack of insulin, but the fact that their bodies have become less sensitive to it. So a common side-effect is that too much glucose is taken out of the blood, causing a potentially dangerous drop in vital glucose supplies to the brain. That’s along with gastrointestinal
problems such as nausea, vomiting and diarrhoea, or constipation, as well as weight gain.

But if you thought Sulfonylureas were unappealing compared with changing your diet and supplementing with the likes of cinnamon, how about the glitazones? They are relatively new, and they work by making cells more sensitive to the effects of insulin. However, they already have a history of dangerous side- effects. The first brand to arrive on the market (Rezulin) was banned in the US in 2000 due to deaths from liver failure. In 2002 a later version was also found to do the same.[12] They’ve also been linked with heart failure and a build-up of fluid in the lungs (pulmonary oedema).[13] They also cause weight gain.[14]

Even more worrying is the latest variant on glitazones, which both increase insulin sensitivity and raises levels of the ‘good’ cholesterol HDL. One of these, Pargluva (Muraglitazar) was recently approved by the US Food and Drug Administration. However, a controlled trial published at the same time, in 2005, found it more than doubled the incidence of deaths, heart attacks or strokes, even though this trial had specifically excluded people with cardiovascular problems.[15]

So what does food have to offer and what is the evidence? A common objection to the nutrition approach is that people don’t stick to dietary changes. However, a placebo-controlled diet run over three years that compared metformin with diet and exercise produced dramatic results. Among those who made the lifestyle changes, 41% were no longer glucose intolerant compared with only 17% of those on metformin, making lifestyle change more than twice as effective.[16]

Since the central problem with diabetes is poor regulation of blood sugar it makes a lot of sense to adapt your diet so that it is ‘low glycaemic’. That means you largely cut out foods that release glucose fast, such as sugar and refined flours and concentrate on foods rich in fibres, proteins and healthy fats.

Low Glycaemic Diets (GL)

The clinical director of the UK National Obesity Forum is in favour of this approach. Study after study has shown that low-GL (glycaemic load) diets not only cause rapid weight loss but also improve insulin resistance and fasting glucose (which is the concentration of glucose remaining in your blood after you have not eaten for eight to twelve hours).[17,18] In animal studies, it’s well known that a low-GL diet rapidly improves blood-sugar control and pancreatic function.[19]

Back in the early 1990s, researchers at the Harvard School of Public Health in the US monitored the health of over 100,000 middle-aged men and women for six years, and found that those who ate a high-GL diet were one-and-a-half times more likely to develop diabetes than those who ate a low-GL diet.[20,21]

Supplements

What’s more, you can combine eating low GL with a couple of food supplements that at first sight look distinctly odd, but again have good evidence backing them up. Research at the Department of Agriculture’s Human Nutrition Research Centre in Beltsville, Maryland, has found that an ingredient in cinnamon mimics insulin, activates its receptor, and works synergistically with insulin in cell – improving glucose metabolism twenty-fold. One study in 2003 found those getting cinnamon had blood-sugar levels 20 per cent lower than those in the control group.[22]

As for chromium, it is actually a mineral that insulin needs to work properly; it makes cells more sensitive to insulin’s effects. In fact many people with blood-sugar problems turn out to be chromium deficient. Again, there is a certain amount of evidence supporting its use. A Chinese study published in 1999 gave 833 patients with Type 2 diabetes 500mcg of chromium picolinate for ten months, which produced a major improvement in blood-sugar levels, and reduced typical diabetes symptoms, including fatigue, thirst and frequent urination.[23]

Another study combined chromium with the B-vitamin biotin, also vital for insulin receptors to work, and found it produced a 26mg/dL drop in fasting blood glucose.[24] Compare that with what happened to patients taking metformin in a key 2002 study comparing metformin with diet.[25] During the first six months of taking metformin, the subjects’ average fasting blood glucose dropped by only about 3mg/dL

Conclusion

The anti-nutrition lobby can always point to need for more studies, ignoring that fact that ninety percent of clinical research in the UK is paid for by the drug companies who are not interested in doing any such thing. But just compare the dangers of the drug approach – weight gain, nausea and vomiting, not to mention heart attacks and liver failure – with those you put yourself at risk from with nutrition.

The only side-effects of a low-glycaemic diet are weight-loss and greater energy, while cinnamon is obviously entirely safe. Then, according to a report published by the World Health Organization, based on a trial with rats, you’d need to take 20,000,000mcg of chromium – that’s 100,000 regular chromium supplements a day – to reach toxic levels.[26]

It does seem perverse that this is form of medicine that is shoved out on the margins due to lack of evidence.

References

1.    Pharmalive.com. Top 500 prescription drugs. Med Ad News. May 2005.
2.    C. Nathan. Antibiotics at the crossroads. Nature. 43: 21 October 2004.
3.    C. Nathan. Antibiotics at the Crossroads. Nature. 43: 21 October 2004.
4.    S. Morgan et al. “Breakthrough” Drugs and Growth in Expenditure on Prescription Drugs in Canada. BMJ. 331: 815-816. 2005.
5.    Editor’s choice Can we tame the monster? BMJ. 333: 8 July 2006.
6.    Drug Industry: Human Testing Masks Death, Injury; Compliant FDA. 2 November 2005, available at http://www.bloomberg.com/apps/news?pid=specialreport&sid=aspHJ_sFen1s&refer=news
7.    R. Evans and S. Bosely. The drugs industry and its watchdog: a relationship too close for comfort. Guardian. 4 October 2004.
8.    Upset and Angry at Lack of Action. BBC News Online. Sunday 3 October 2004
9.    Radley D C et al. Off-label Prescribing Among Office-Based Physicians. Arch Intern Med. 166:1021-1026. 2006.
10.    F.Hu et al. Fish and Omega-3 Fatty Acid Intake and Risk of Coronary Heart Disease in Women. Journal of the American Medical Association. 287(14): 1815-21. 2002.
11.    D. Buvat.  Letter: Use of Metformin is Cause of Vitamin B12 Deficiency. American Family Physician. 15 June 2004
12.    L. D. May et al. Mixed Hepatocellular-Cholestatic Liver Injury After Pioglitazone Therapy. Ann Intern Med. 136(6): 449-52. 2002m.
13.    A. Garg. Thiazolidinedione-Associated Congestive Heart Failure and Pulmonary Edema. Mayo Clinic Proceedings. 78: 1088. 2003.
14.    US Food and Drug Administration Medical Officer. Review of Rosiglitazone (Avandia), 40: 16 April 1999
15.    Nissen SE, Wolski K, Topol EJ. Effect of Muraglitazar on Death and Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus. JAMA. 294(20): 2581-6. 2005.
16.    T. Orchard et al. The Effect of Metformin and Intensive Lifestyle Intervention on the Metabolic
Syndrome: The Diabetes Prevention Program Randomized Trial. Ann Intern Med. 142(8): 611-9. 2005.
17.    M. Pereira et al. Effects of a Low-Glycemic Load Diet on Resting Energy Expenditure and Heart Disease Risk Factors During Weight Loss. JAMA. 292: 2482-2490. 2004.
18.    La Haye SA et al. Comparison Between a Low Glycemic Load Diet and a Canada Food Guide Diet in Cardiac Rehabilitation Patients in Ontario. Can J Cardiol. 21(6): 489-94. 2005.
19.    D.B. Pawlak et al. Effects of dietary glycaemic index on adiposity, glucose homeostasis and plasma lipids in animals. The Lancet. 364(9436): 778-85. 2004.
20.    J. Salmeron et al. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA. 277(6): 472-7. 1997.
21.    J Salmeron et al. Dietary Fiber, Glycemic Load, and Risk of NIDDM in Men. Diabetes Care. 20: Issue 4: 545-550. 1997.
22.    A Khan et al. Cinnamon Improves Glucose and Lipids of people with Type 2 Diabetes. Diabetes Care. 26: 3215-3218. 2003.
23.    N. Cheng et al. Follow-up Survey of People in China with Type 2 Diabetes Mellitus Consuming Supplemental Chromium. J Trace Elem Exp Med. 12: 55-60. 1999.
24.     McCarty MF. High-Dose Biotin, an Inducer of Glucokinase Expression, May Synergize with Chromium Picolinate to Enable a Definitive Nutritional Therapy for Type II Diabetes. Review. Med Hypotheses. 52(5): 401-6. 1999.
25.    Knowler et al. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. NEJM. 246: 393-403. 2002.
26.    JA Janus and EI Kranjnc Integrated Criteria Document Chromium: Effects. Appendix. Bilthoven, Netherlands: National Institute of Public Health and Environment Protection. 1990.

Further Information

Food Is Better Medicine Than Drugs: Your Prescription for Drug-Free Health by Jerome Burne and Patrick Holford. (Piatkus 2006). Reviewed in issue 130. Is available from www.amazon.co.uk