As the age of personalised medicine approaches, innovative researchers are rethinking the way we conduct clinical studies. “Rethinking” in radical ways – think: individualised clinical trials!
One obvious question is: Can you really conduct a clinical trial involving just one participant?
In this post, we will look at some of the ideas and evaluate the strengths and weaknesses these approaches.
A Nobel prize medal. Source: Motley
In the annals of Nobel prize history, there are a couple winners that stands out for their shear….um, well,…audacity.
One example in particular, was the award given to physician Dr Werner Forssmann. In 1956, Andre Cournand, Dickinson Richards and Forssmann were awarded the Nobel Prize in Physiology or Medicine “for their discoveries concerning heart catheterisation and pathological changes in the circulatory system”. Forssmann was responsible for the first part (heart catheterisation).
In 1929, at the age of 25, Forssmann performed the first human cardiac catheterisation – that is a procedure that involves inserting a thin, flexible tube directly into the heart via an artery (usually in the arm, leg or neck). It is a very common procedure performed on a daily basis in any hospital today. But in 1929, it was revolutionary. And the audacious aspect of this feat was that Forssmann performed the procedure on himself!
And if you think that is too crazy to be true, please read on.
But be warned: this particular story gets really bonkers.
Numerous epidemiologic studies have indicated that coffee consumption reduces the risk of Parkinson’s disease. For a long time, efforts have been made to determine what the magic ingredient in this popular beverage is. Many people have speculated that the stimulant caffeine is the critical active ingredient in this neuroprotective effect.
New research, however, suggests that this may not be the case.
Today’s post will review recently published results suggesting that Quercetin (and not caffeine) is the neuroprotective component in coffee.
Kaldi the goat herder. Source: CoffeeCrossroads
Legend has it that in 800AD, an Ethiopian goat herder called Kaldi noticed that his animals were “dancing” after eating some berries from a tree that he did not recognise. Fascinated by the happy behaviour of his goats, Kaldi naturally decided to eat the berries for himself and he subsequently became “the happiest herder in happy Arabia”.
This amusing encounter was apparently how humans discovered coffee. It is most likely a fiction as the earliest credible accounts of coffee-consumption emerge from the 15th century in the Sufi shrines of Yemen, but since then coffee has gone on to become one of the most popular drinks in the world.
Stupid question: what exactly is coffee?
For a person who doesn’t drink coffee (like myself), this is actually a really interesting question. Coffee is a beverage made from ground up roasted beans, which are the seeds of berries from the Coffea plant. These are the berries:
Coffea berries. Source: About.me
And these are the beans (unroasted):
Unroasted Coffee beans. Source: Kopiholic
There are basically two types of coffee beans: Arabica and Robusta.
Approximately 70 percent of the coffee beans we use are Arabica. Surprisingly, the less popular Robusta actually has twice as much caffeine as Arabica. And caffeine is the stimulant that rewards people for drinking this beverage.
Caffeine is also the chemical that has long been thought to have positive effects on Parkinson’s disease, possibly even reducing the risk of the condition (more on that below).
Fancy a cuppa? Source: Science-All
What does coffee have to do with Parkinson’s disease?
We have previously discussed the enormous contribution that the Honolulu Heart Study has made to our understanding of Parkinson’s disease (click here to read that post). Many of the earliest associations with the condition were found in that large epidemiologic study. One of those findings was that the consumption of coffee reduced one’s risk of developing Parkinson’s disease.
Title: Association of coffee and caffeine intake with the risk of Parkinson disease.
Authors: Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR.
Journal: JAMA. 2000 May 24-31;283(20):2674-9.
PMID: 10819950 (This article is OPEN ACCESS if you would like to read it)
The researchers behind this article analysed the data from the Honolulu Heart Study – an epidemiological study of 8,006 “non-institutionalized men of Japanese ancestry, born 1900-1919, resident on the island of Oahu” – and found that the age-adjusted incidence of Parkinson’s disease declined consistently with increased amounts of coffee intake (from 10.4 per 10,000 person-years in men who drank no coffee to 1.9 per 10,000 person-years in men who drank at least 28 oz/d). This and other findings in their analysis indicated that higher coffee (and caffeine) intake is associated with a significantly lower incidence of Parkinson’s disease.
Subsequent studies have replicated this association, and several have demonstrated the neuroprotective effects of caffeine (click here for a review on this topic).
So what new data has been published?
This is Prof Patrick and Prof Edith McGeer:
Prof Patrick and Prof Edith McGeer. Source: Mcgeerandassociates
This husband and wife team of scientists are well recognised figures within the Parkinson’s disease research work, having produced many seminal scientific reports. Patrick is a particularly interesting character having played basketball for Canada in the 1948 Olympics and then a politician in the British Columbia legislature (1962-1986).
They are also authors on the article we are going to review today:
Title: Quercetin, not caffeine, is a major neuroprotective component in coffee.
Authors: Lee M, McGeer EG, McGeer PL.
Journal: Neurobiol Aging. 2016 Jul 5;46:113-123.
As we said above, for the longest time people have believed that caffeine was the active ingredient in the miraculous ability of coffee to reduce the risk of Parkinson’s disease. The researchers who published this report were particularly interested in the neuroprotective role for coffee in Parkinson’s disease and they decided to break coffee down into some of its basic components. Specifically:
- Chlorogenic acids (CGAs)
They tested each of these coffee components on cells (grown in petri dishes) that had been exposed to a toxin, and then assessed cell survival. Curiously, although caffeine did exhibit neuroprotective effects on the cells, it was beaten by the far superior protective effects of quercetin.
What is quercetin?
Quercetin is a flavonoid (a type of plant pigment) that is found in many fruits, vegetables, leaves and grains. Flavonoids are potent antioxidants. Antioxidants scavenge particles (called free radicals) in the body which can damage cell membranes, affect DNA, and even cause cell death. Antioxidants neutralize these free radicals. (For more on flavonoids – click here).
What does this mean?
The results are very interesting, especially if they provide us with a new potential target for therapeutic drug development. It also raises the age-old idea of antioxidants being potentially useful in the treatment of Parkinson’s disease (the previous history of this therapeutic approach has been disappointing – click here to read more on this).
But before you rush out and load up on quercetin, there are a few things to consider:
Quercetin is generally considered pretty safe. Fruits and vegetables are the primary dietary sources of quercetin, particularly citrus fruits, apples, onions, parsley, sage, tea, and red wine.
That said: excessive use of quercetin can have side effects, which may include headache and upset stomach. Very high doses of quercetin can cause damage to the kidneys (doses greater than 1 g per day), and regular periodic breaks from taking quercetin is advised. Importantly, pregnant women, breastfeeding women, and people with kidney disease should avoid quercetin.
EDITOR’S NOTE: If you are considering supplementing your diet with quercetin (or any other potential therapeutic agents) please firstly discuss this change of lifestyle with your medical physician. Information provided here can under no circumstances be considered medical advice.
Having said that we shall keep an eye out for any new research of quercetin and Parkinson’s disease, and report it here.
The banner for today’s post was sourced from Phoxpopmagazine
In 1950, Dr Tavia Gordon noticed that while the overall mortality rates for men in the USA and Japan were very similar, the incidence of heart disease was significantly lower in Japan. This observation resulted in three longitudinal studies – one of which became known as the Honolulu Heart Study.
Dr Travis Gordon. Source: JSTOR
The original purpose of the study was to determine whether there was a difference in heart disease incidence between Japanese people living in Japan and individuals of Japanese ancestry living in Hawaii.
The subjects recruited for the study were “non-institutionalized men of Japanese ancestry, born 1900-1919, resident on the island of Oahu.” In all, 12,417 men were identified as meeting the criteria. Of those contacted, 1,269 questionnaires were ‘return to sender’, 2,962 men declined to participate in the study, and 180 died before the study commenced. That left 8,006 participants who would be studied and followed for the rest of their lives.
From October 1965 onwards, the participants were interviewed and given physical examinations every few years. The interview processed asked for:
- Family and personal history of illness
- Sociological history
- Smoking status
- Physical activity level
The physical examination was very thorough, looking at:
- ECG (Electrocardiography – electrical activity of the heart)
- Urine analysis
- Measurements of weight, height, skinfold thickness, etc.
- Blood pressure and serum cholesterol
As a result, the study built up a HUGE amount of epidemiological information regarding these 8,006 individuals.
So, what does this have to do with Parkinson’s disease????
Given the enormous number of individuals involved in the study and the length of time that they were followed, it was inevitable that a certain percentage of them would develop Parkinson’s disease as the study progressed. As a result, the Honolulu Heart Study represents one of the largest epidemiological study of Parkinson’s to date. In 1994, a group of research involved in the study, published some very interesting findings relating to Parkinson’s disease. That published article was:
Title: Epidemiologic observations on Parkinson’s disease: incidence and mortality in a prospective study of middle-aged men.
Authors: Morens DM, Davis JW, Grandinetti A, Ross GW, Popper JS, White LR.
Journal: Neurology, 1996 Apr;46(4):1044-50.
In total, 92 of the 8006 individuals enrolled in the study developed Parkinson’s disease. The incidence of Parkinson’s cases was registered between 1965 and November 30th 1994. The majority of the cases were diagnosed between 55 and 79 years of age (n=80). Diagnosis after the age of 80 was very rare. It is interesting to note that when the researchers divided the group into those ‘born before 1910’ and those ‘born after 1910’, the older group (born before 1910) had a lower risk of Parkinson’s disease.
In another study, the same group of investigators noted
Title: Prospective study of cigarette smoking and the risk of developing idiopathic Parkinson’s disease.
Authors: Grandinetti A, Morens DM, Reed D, MacEachern D.
Journal: American Journal of Epidemiology 1994 Jun 15;139(12):1129-38.
In this study the authors found that men who had smoked cigarettes at any time prior to their enrollment in the study in 1965, had a reduced risk of developing idiopathic Parkinson’s disease (relative risk = 0.39). That is to say, smoking reduced the chance of developing Parkinson’s disease. And a few years later the authors published a follow up paper which rejected the possibility that smoking was killing people before they could develop Parkinson’s disease (selective mortality representing a false positive). That follow up report can be found here.
EDITOR’S NOTE: THIS DOES NOT MEAN THAT EVERYONE SHOULD RUSH OUT AND START SMOKING. THERE DOES, HOWEVER, APPEAR TO BE SOME INGREDIENT IN CIGARETTES THAT REDUCES THE INCIDENCE OF PARKINSON’S DISEASE. A LOT OF RESEARCH IS CURRENTLY TRYING TO IDENTIFY THAT INGREDIENT.
This finding was made alongside other interesting correlations (Note: coffee and alcohol reduce the risk of Parkinson’s disease):
From Grandinetti et al (1994).
It should be noted that many of these associations (smoking in particular) had been reported before, but the Honolulu Heart Study was the first epidemiological study providing definitive proof. And it should be noted that subsequent epidemiological studies have found similar results.
INTERESTING FACTS ABOUT THE JAPANESE:
- The Japanese as a population have a lower incidence of Parkinson’s disease (much like most of the Asian nations) than their western equivalents, despite living longer.
- Japan is the only country in the world where females have a higher incidence of Parkinson’s disease than men (and we have no idea why!). Look here for more on this.