ATMS reports that one of the largest – and lengthiest – studies involving patients suffering mild-to-moderate Alzheimer’s disease has revealed that a daily 2000 international unit (IU) supplement of vitamin E has the power to slow functional decline.

Reported in the January 1, 2014 issue of the Journal of  the American Medical Association (JAMA), the double-blind trial, conducted between 2007 and 2012, involved 613 predominantly male patients at 14 Veterans Affairs medical centres in the US. All of the participants were taking the acetylcholinesterase inhibitor drug donepezil (Aricept) to increase the level and duration of action of the neurotransmitter acetylcholine.

Patients were divided into four roughly equal groups to receive one of the following each day:

• 2000IU vitamin E.
• 20 milligrams of the Alzheimer’s drug memantine (Namenda), a drug that blocks the activity of glutamate to slow the late stages of the disease.
• A combination of vitamin E and memantine.
• A placebo.

During the average follow-up period of 2.3 years the researchers, lead by Maurice Dysken M.D., a research scientist at the Minneapolis V A Health Care System, monitored changes in participants’ functional decline. Defined as the patient’s lack of ability to carry out everyday tasks without assistance, functional decline has a significant impact on a patient’s quality of life in addition to imposing a strain on social and economic costs.

Using the Alzheimer’s Disease Cooperative Study/Activities of Daily Living, the researchers looked at aspects such as:

• The person’s ability to perform activities of daily living.
• Their cognitive function.
• Memory and language.
• Psychological and behavioural problems.
• Time necessitating caregiver assistance.

Surprising results

The results were surprising. The drug memantine taken alone, or in combination with vitamin E, produced no benefits. However, when vitamin E was taken alone functional decline slowed by 19 per cent compared with patients who received the placebo. This translates to what the researchers describe as a “clinically meaningful delay in progression of 6.2 months.”

Moreover, those in vitamin-only group needed two hours less assistance from a caregiver each day. Dr Dysken remarked that this could represent the difference between patients who can still dress or bathe independently and those who cannot.

This is the first large-scale clinical trial to assess not only the effectiveness of alpha tocopherol in patients with mild-to-moderate Alzheimer’s disease, but also the combination of alpha tocopherol and memantine.

The research team pointed out that in contrast to the conclusion drawn from a 2005 meta-analysis of vitamin E, which showed high-dose vitamin E may actually increase the risk of all-cause mortality, this study found no significant increase in mortality with vitamin E. The annual mortality rate was 7.3 per cent in the alpha tocopherol group, compared with 9.4 per cent for the placebo group.

In fact, the finding of this study adds weight to previous studies investigating the use of alpha tocopherol in patients with severe Alzheimer’s disease, including one 1997 study that revealed that a 2000IU dose of the antioxidant vitamin was effective in slowing progression of moderately severe Alzheimer’s disease.

Exercise may be just as effective as drugs for treating a range of health conditions, including coronary heart disease and stroke, according to a study published in the British Medical Journal in October 2013.

Researchers Huseyin Naci, an HMS visiting fellow in population medicine at the Harvard Pilgrim Health Care Institute, and a graduate student at the London School of Economics; and Dr John Ioannidis, director of the Stanford Prevention Research Center at the Stanford University School of Medicine, analysed the results of 305 randomised controlled trials involving 339,274 participants in order to compare the effectiveness of exercise versus drugs on mortality across four conditions:

• Secondary prevention (defined as treating patients with existing disease before it causes significant illness) of coronary heart disease.
• Rehabilitation of stroke.
• Treatment of heart failure.
• Prevention of diabetes.

These are the only conditions where studies on the effects of exercise on reducing mortality have been undertaken.

While most of the participants in all the analysed trials had taken drugs, a mere 14,716 participants from 57 of those trials had been involved in exercise-based interventions. Typically a component of rehabilitation programs, these exercise interventions mostly involved walking or other aerobic routines, although in some instances they consisted of weight training or other exercises. Still, the number was sufficiently large for Naci and Ioannidis to create an elaborate network of cross references, comparing the outcomes when people received certain drugs, followed exercise regiments or – on rare occasions – both.

Findings

The study – the first of its kind to use statistical techniques of network meta-analysis to compare these different health interventions – found:

• People undergoing secondary prevention of heart disease, who exercised but did not use commonly prescribed medications including statins, angiotensin-converting-enzyme inhibitors, or anti-platelet drugs, had the same risk of dying from – or surviving – heart disease as patients who took those drugs.
• People being treated for prevention of diabetes who exercised had the same relative risk of dying from the condition as those taking the most commonly prescribed drugs.
• People who had suffered a stroke and who exercised had significantly less risk of dying from that condition than if they used medications. However, the study authors note that stroke patients who are able to exercise may have been unusually healthy to start with.
• Diuretics were more effective than exercise in staving off mortality in people suffering chronic heart failure – the only condition where drugs were noticeably more effective than exercise.

Evidence blind spot

Naci remarked that while considerable literature exists on the medical benefits of exercise alone, and on the life-saving benefits of some drugs, there is little that compares them directly – and this was the rationale behind this study. This lack of existing evidence may actually have impacted the results. The blind spot – as the researchers describe it – in available scientific evidence prevents prescribers and their patients from understanding the clinical circumstances where drugs might provide only modest improvement, but exercise could yield more profound or sustainable gains in health.

The results also underscore the dearth of research on exercise as a medical intervention. Ioannidis says far more information is needed about how exercise compares with drugs in treating many conditions, as well as the types and amounts of exercise that confer the greatest benefits and whether there are side effects such as injuries. He would love to see pharmaceutical companies set aside a tiny fraction of their profits for such studies, but doubts such funding will materialise without widespread public pressure.

Potent treatment for heart disease

Overall, Ioannidis comments, the study results suggest that exercise can be quite potent in treating heart disease and the other conditions, equalling the lifesaving benefits available from many commonly prescribed  drugs, including the controversial statins.

So until more research is undertaken, exercise should be considered as either a viable alternative, or a complementary treatment, to drug therapy. However, Naci stresses that patients should always consult their doctors before stopping their medication, as one study is not sufficient evidence for people to give up prescribed drugs. He suggests people think long and hard about their lifestyles and talk to their doctors about whether exercise could and should be incorporated into their care.

Written by Rosemary Ann Ogilvie for the Australian Traditional Medicine Society (ATMS)