Tagged: HPFS

The benefits (???) of Antioxidants

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It seems everyday we read stories in the media about the benefits of these things called antioxidants. We are repeatedly told that we ‘need more antioxidants in our diet’, because they will help to stave off debilitating conditions like Parkinson’s disease.

Last week, however, a study was published which indicates that this may not be the case.

In todays post we look at antioxidants and their impact on Parkinson’s disease.


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Berries are a wonderful source of antioxidants. Source: Steroidal

Antioxidants are one of those subjects that is often discussed, but not well understood. So before we review the study that was published last week, let’s first have a look at what we mean when we talk about antioxidants.

What is an antioxidant?

An antioxidant is simply a molecule that prevents the oxidation of other molecules.

OK, but what does that mean?

Well, the cells in your body are made of molecules. Molecules are combinations atoms of one or more elements joined by chemical bonds. Atoms consist of a nucleus, neutrons, protons and electrons.

Oxidation is the loss of electrons from a molecule, which in turn destabilises the molecule. Think of iron rusting. Rust is the oxidation of iron – in the presence of oxygen and water, iron molecules will lose electrons over time. Given enough time, this results in the complete break down of objects made of iron.

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Rust, the oxidation of metal. Source: TravelwithKevinandRuth

The exact same thing happens in biology. Molecules in your body go through a similar process of oxidation – losing electrons and becoming unstable. This chemical reaction leads to the production of what we call free radicals, which can then go on to damage cells.

What is a free radical?

A free radical is an unstable molecule – unstable because they are missing electrons. They react quickly with other molecules, trying to capture the needed electron to re-gain stability. Free radicals will literally attack the nearest stable molecule, stealing an electron. This leads to the “attacked” molecule becoming a free radical itself, and thus a chain reaction is started. Inside a living cell this can cause terrible damage, ultimately killing the cell.

Antioxidants are thus the good guys in this situation. They are molecules that neutralize free radicals by donating one of their own electrons. The antioxidant don’t become free radicals by donating an electron because by their very nature they are stable with or without that extra electron.

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How free radicals and antioxidants work. Source: h2miraclewater

What are good sources of antioxidants?

While human being are pretty poor at producing antioxidants, plants produce LOTS! Thus vegetables and fruits are a fantastic source of antioxidants.

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Sources of antioxidants (no. 3 is our favourite). Source: DrAxe

The Oxygen radical absorbance capacity (ORAC) score mentioned in the figure above is a method of measuring the antioxidant capacity of various substances. For comparative sake, a piece of tofu has an ORAC score of approximately 90, a beef steak has an ORAC score of approximately 10, and a ‘Redbull’ energy drink has an ORAC score of 0 (as they all have very few antioxidants – Source:Superfoodly).

A source of major antioxidants are vitamins (such as beta-carotene, vitamin C, and vitamin E). Vitamins are essential nutrients that our bodies needs (in small amounts) to function properly. Many of them are also potent antioxidants.

Vitamin C (or ascorbic acid), in particular, is a powerful antioxidant and it is found in both animals and plants. Unfortunately for humans, however, one of the enzymes needed to make ascorbic acid was lost by a genetic mutation during primate evolution, and so we must obtain it from our diet (eat lots of oranges folks).

How could antioxidants work for Parkinson’s disease?

 

Postmortem analysis of the brains of people who had Parkinson’s disease has revealed numerous signs of oxidative damage, and this has lead to many researchers hypothesising that oxidation is a key component of the disease.

So what research was published last week?

The results of this study:

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Title: Intake of antioxidant vitamins and risk of parkinson’s disease.
Authors: Hughes KC, Gao X, Kim IY, Rimm EB, Wang M, Weisskopf MG, Schwarzschild MA, Ascherio A.
Journal: Movement Disorders. 2016 Oct 27. doi: 10.1002/mds.26819.
PMID: 27787934

In this study, the investigators wanted to look at the consumption of antioxidant vitamins and the risk of developing Parkinson’s disease. In order to do this, they needed large pools of medical data that they could analyse. They used the databases from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) in the USA.

NHS study was started in 1976 when 121,700 female registered nurses (aged 30 to 55 years) completed a mailed questionnaire. They provided an overview of their medical histories and health-related behaviours. The HPFS study was established in 1986, when 51,529 male health professionals (40 to 75 years) responded to a similar questionnaire. Both the NHS and the HPFS send out follow-up questionnaires every 2 years.

The investigators in the current study, removed the data from people who reported ‘implausible total energy intake at baseline (<660 or >3,500 kcal/day for women and <800 or >4,200 kcal/day for men)’, missed reporting for any survey, or had a diagnosis of Parkinson’s disease at the start of the study. This left them with the survey results of 80,750 women and 48,672 men to analyse.

From these pools of subjects, they found a total of 1036 people with Parkinson’s disease (554 in HPFS and 482 in NHS). When the investigators looked at antioxidant vitamin consumption, they found that vitamin E was not associated with an increased or decreased risk of Parkinson’s disease. Vitamin C intake showed indications of reducing the risk of developing Parkinson’s, but this not significant.

The investigators concluded that their results do not support the hypothesis that consumption of antioxidant vitamins reduces the risk of Parkinson’s disease.

What about other Parkinson’s disease research on antioxidants?

There have been several clinical trials for antioxidants and Parkinson’s disease. Of particular interest has been the research surrounding Coenzyme Q10 (also known as ubiquinone and ubidecarenone).Coenzyme Q10 is an antioxidant that exhibited positive preclinical results for Parkinson’s disease, and this led to several large clinical trials:

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Title: A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.
Authors: Parkinson Study Group QE3 Investigators., Beal MF, et al.
Journal: JAMA Neurol. 2014 May;71(5):543-52.
PMID: 24664227

This article reported the results of a phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites, consisting of 600 participants. While Coenzyme Q10 was safe and well tolerated by the subjects in the study, it demonstrated no evidence of clinical benefit.

One justified critique of this study, however, was the variety of subjects with Parkinson’s disease involved in the study. It has been suggested that a clinical trial should be performed with coenzyme Q10 in people with Parkinson’s disease who have a proven mutation in the PINK1 gene as these are the subjects who are most likely to benefit from this approach. That would be an interesting trial.

So what does it all mean?

Well, the study published last week needs to be replicated with another large database before any serious conclusions can be made. For all the hype around antioxidants, however, there is a worrying lack of supporting evidence that they actually have any effect (in the case of lung cancer there are even suggestions that some vitamin antioxidants could exacerbate the situation – click here for more on this).

The results of the study reviewed above do suggest that our view of oxidation in Parkinson’s disease needs to be re-addressed. It may be that oxidation may simply be an end step in the condition, and trying to block it with antioxidants is fruitless.

It should be noted that we are not suggesting here that people should stop taking antioxidants – they are an important part of any balanced diet, necessary for normal biological functioning. We are simply presenting the evidence that some of the hype surrounding their potential is unfounded.

As usual, as more information comes to hand, we shall present it here. Watch this space.


The banner for todays post was sourced from Pinkhope

“Red hair, sir, in my opinion, is dangerous”

Henna-Hair-Red-Hair-Ginger-Hair-Benefits-Beauty

The quote entitling this post is from a PG Wodehouse book ‘Very Good, Jeeves!’.


We have previously discussed the curious connection between melanoma and Parkinson’s disease. There is also a well known connection between melanoma and red hair. And believe it or not, there is another really strange relationship between Parkinson’s disease and red hair.

Redhair

Title: Genetic determinants of hair color and Parkinson’s disease risk.
Authors: Gao X, Simon KC, Han J, Schwarzschild MA, Ascherio A.
Journal: Ann Neurol. 2009 Jan;65(1):76-82.
PMID: 19194882

In 2009, researchers from Harvard University found a relationship between hair color and risk of Parkinson’s disease, when they examined the records of 131,821 US men and women who participated in the two large longitudinal studies, the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS).


The HPFS, which started in 1986, sends questionnaires to US health professionals (dentists, optometrists, etc) – aged 40-75.  Every couple of years, members of the study receive questionnaires dealing with diseases and health-related issues (e.g. smoking, physical activity, etc). The questionnaire is supplemented by another questionnaires which is sent every four years, that deals with dietary information.

The NHS study – which was established in 1976 and then expanded in 1989 – has also collected questionnaire-based information from 238,000 registered nurses. Similar to the HPFS, every two years the study participants receive a questionnaire dealing with diseases and health-related topics.


In their study, the investigators found 264 of the male and 275 of the female responders to the HPFS and NHS questionnaires had been diagnosed with Parkinson’s disease. Of these individuals, 33 were black haired, 418 had brown hair, 62 were blond and 26 were redheads. Given that redheads make up just 1% of the general population but 5% of the people who were diagnosed with Parkinson’s disease in their study, the authors suggested that red haired people have a higher risk of developing Parkinson’s disease. Interestingly, they found a stronger association between hair color and Parkinson’s disease in younger-onset of PD (that is being diagnosed before 70 years of age) than those with age of onset greater than 70 years. When they took health and age related matters into account, the authors concluded that people with red hair are almost four times more likely to develop Parkinson’s disease than people with black hair.

NOTE: This result does not mean that people with red hair are definitely going to develop Parkinson’s disease, it simply suggests that they may be more vulnerable to the condition. And we should add that this result have never been replicated and we are not sure if anyone has ever attempted to reproduce it with a different database.

So how does (or could) this work?

The short answer is: we really don’t know.

The long answer involves explaining where there are no connections:

Red hair results from a genetic mutation. 80% of people with red hair have a mutation in a gene called MC1R – full name: melanocortin-1 receptor. Another gene associated with red hair is called HCL2 – ‘Hair colour 2’. We know that the connection between red hair and Parkinson’s disease is not genetic, as there is no association between MC1R mutations and Parkinson’s disease (for more on this, click here). We are not sure about HCL2, but this gene has never been associated with any disease.

What we do know is that redheads:

  • are more sensitive to cold (for more on this, click here)
  • are less responsive to subcutaneously (under the skin) administered anaesthetics (for more on this, click here)
  • suffer more from toothaches (for more on on this, click here)
  • are more sensitive to painkillers (for more on this, click here)
  • require more anesthetic for surgery (for more on this, click here)

Common myths associated with red hair include:

  • redheads bled more than others (this is not true – click here)…but they do bruise easier!
  • redheads are at greater risk of developing endometriosis (this is not true – click here)
  • redheads are more frequently left-handed (I can find no evidence for this, so I’ll put it in the myth basket until corrected).

There is also a strange link between red hair and multiple sclerosis, but it is too complicated to understand at the moment (women with red hair are more vulnerable to multiple sclerosis than men with red hair, for more on this, click here).

How any of these findings relates to Parkinson’s disease is unclear – we provide them here for those who are interested in following up this curious relationship.

One important caveat regarding this study is that incidence rates of Parkinson’s disease in countries with very high levels of red hair do not support the relationship (PD & red hair). In Scotland, approx. 10% of the population have red hair (source), and yet the England has a higher incidence of Parkinson’s disease (28.0/10,000 in England vs 23.9/10,000 in Scotland – source).

It may well be, however, that there is no direct connection between red hair and Parkinson’s disease. And until the results of the 2009 study mentioned above are replicated or supported by further findings, we here at the ‘Science of Parkinson’s disease’ shall consider this simply as a curious correlation.