Tuesday, December 3, 2013

Why you should support open access science


When writing the last blog post, I included references for further reading.  If anyone who was not affiliated with a university tried to read these papers, you would find that you would have to fork over $30 or so per paper to view anything besides the abstract.  Considering that reading one of these articles may stir your interest in further research, you could quickly find yourself on a very expensive paper journey.  It was from the frustration with this ensconced system that the open access movement was born.
Before I describe what open access means, I thought I’d give a brief description of the publishing process.  The life of a scientific paper begins as a manuscript, written by scientists to communicate their latest results.  Once the manuscript is complete, it is submitted to a journal of the author’s choosing.  The staff of the journal first assesses whether the manuscript fits their organization’s specific scope.  If so, they send the manuscript to two to three reviewers, who are experts in a specific field, for example professors at a research university.  The reviewers determine whether the science is sound and give their opinion whether they think the manuscript should be published.  They send this information back to the journal editor, who then makes the final decision as to the fate of the manuscript. Historically, subscription and advertising fees supported most peer-reviewed journals.
With the popularization of the Internet, publishing scientific articles online became easy and inexpensive.  This technology facilitated the creation of the open access movement.  The main tenet of open access, as outlined in the 2002 Budapest Open Access Initiative is that literature “should be freely accessible online.”  Publishing articles on the internet not only increases the speed at which information can be shared, but it can also be done at a much higher volume as compared to print.
Access to scientific research at no cost benefits society in a number of ways.  For instance, it assists small businesses in cost savings when developing new techniques.  Subscription fees for non-open access journals are quite expensive, often prohibiting readership from those with less capital such as universities in developing countries.  Therefore open access journals bolster research programs at these institutions.  Finally, free scientific articles allow healthcare professionals (e.g. physicians, physician assistants and nurses) to keep up with the latest research, which helps them to make more informed decisions when treating their patients.
Recently Dr. John Bohannon, a reporter at Science, exposed a downfall of the rapidly growing open access publishing industry.  He concocted a manuscript describing a fake anticancer drug candidate.  He purposefully included flawed experiments that “any reviewer with more than a high-school knowledge of chemistry and the ability to understand a basic data plot should have spotted.”  He submitted different versions of this faux article to 304 open access journals.  Surprisingly, more than half of them accepted the manuscript, many of which without any apparent peer review.  This sting reveals the predatory nature of some of the budding open access journals and also the lack of quality peer review.  Hopefully Dr.Bohannon’s exposé will motivate open access publishers to address their weaknesses.  
So how do open access journals pay their editorial and IT staff?  Instead of charging for subscriptions, the journals instead charge the authors to publish the articles.  In countries with well-funded research programs, this fee is usually not a concern.  In developing nations, however, the publishing fee could be a major hurdle.  Therefore many open access journals offer discounts or fee waivers to those under financial hardships.
You can support open access through Amazon’s Smiles program.  For every eligible purchase you make Amazon will donate 0.5% to the Public Library of Science (PLOS), a nonprofit publisher, to help support authors who cannot afford their publication fees.  (NOTE:  PLOS ONE rejected the faux Science manuscript due to its poor scientific quality.  Also note the impeccable timing of this post, which may or may not be a blatant plug for PLOS!)  This donation costs you no money, so no excuse not to sign up

Saturday, November 2, 2013

What happens when you eat too much protein?


 

           
            An exercise recovery shakes salesman recently posted up outside of our gym, offering free samples to interested members.  Although I do not particularly subscribe to post-workout reconstituted beverages, he piqued my interest.  When I told him that I would like to try the “protein” formulation, he responded, “That has too much protein in it for you.  I’m only going to give you 2/3 a scoop.”  While he measured out my soon-to-be drink, he recommended the “women’s” formulation instead.  I was somewhat taken aback, but his proclaim got me thinking, what does happen when you consume too much protein?  Is my effort to build more muscle instead detrimental to my health?

            Proteins play many roles in biology.  They facilitate biochemical reactions (enzymes).  They serve structural and mechanical functions such as forming scaffolding for cellular structure and executing muscle contraction.  In addition, they often act as signaling molecules that relay messages between cells.  Proteins are synthesized in the cell by linking together building blocks known as amino acids.  There are 20 standard amino acids that represent a variety of different chemical functionalities – acidic, basic, aromatic, polar, and hydrophobic – that can be combined to form proteins with diverse structures and functions.  Humans can create all but 9 of these amino acids themselves, and therefore rely upon their diet to supplement these essential protein building blocks.

            The National Academy of Sciences Institute of Medicine Food and Nutrition Board recommends that both men and women consume “0.8g of good quality protein/kg body weight/d.”  For a 67kg person, like myself, this amounts to roughly 54g of protein/day.  In other words, I should eat 1 cup of cottage cheese and a 3.5 ounce piece of chicken breast (about half of a large chicken breast) per day.  Prior to joining the aerobic/weightlifting/gymnastics cult known as CrossFit, I definitely did not make it a priority to consume protein.  Now I try to consume protein at every meal, which puts me over my daily-recommended intake.  

            After eating your favorite meat/cheese/protein source, the food makes its way from your mouth down to your stomach.  Its acidic environment, combined with enzymes secreted by the cells lining the stomach, break down the proteins into individual amino acids.  As the food travels from the stomach, to the small intestine, and then to the large intestine, different proteases (enzymes that break down proteins) are released to further digest the proteins.  These free amino acids are then absorbed by the epithelial cells lining the respective organ and taken up into the blood stream, through which they make their way to the liver.  Here, transaminases and deaminases (enzymes that transfer and remove amino groups respectively) break down the amino acids into alpha-keto acids and ammonia.  The alpha-keto acids can be utilized for energy production, whereas the ammonia provides a nitrogen source for the biosynthesis of new proteins, nucleotides (DNA and RNA building blocks) or other biological amines.  If there is excess ammonia, it is excreted, for example as urea in urine.  Consumption of protein most importantly provides a nitrogen source for a variety of biomolecules.  When other more easily metabolized sources of energy are low (e.g. carbohydrates or fats), proteins can be used instead.

            But what if not all of the free amino acids are absorbed into the bloodstream?  What if some slip through and are instead exposed to the trillions of bacteria that inhabit our guts?  Our commensal bacterial friends feed on the nutrients that are not readily absorbed by our gastrointestinal tract and generate byproducts that are both beneficial and detrimental.  For example, we cannot readily digest resistant starches and fiber, leaving them for our gut microbes.  They consume these carbohydrates and produce short chain fatty acids (SCFAs), which are an energy source for the cells lining the large intestine.  These SCFAs also have been shown to regulate inflammation and even to help fight off pathogenic bacteria.  In contrast, bacterial fermentation of a subclass of amino acids produces toxic hydrogen sulfide and aromatic compounds (phenols and indoles).  Our liver and kidneys, if functioning properly, neutralize these toxins.  However, these compounds are linked to diseases such as ulcerative colitis and inflammatory bowel disease.

            Protein sources contain other molecules besides proteins and amino acids that have been shown to have adverse health effects.  Choline, a byproduct of a lipid found in plants and animals, is converted by our gut microbiota into trimethylamine (TMA).  Once TMA is absorbed into our liver, it can be oxidized to form trimethylamine-N-oxide (TMAO), which is then released into the bloodstream.  A high concentration of blood plasma TMAO is correlated with cardiovascular disease.  Recently, L-carnitine has also been shown to be converted to TMA and thus TMAO by gut bacteria.  L-carnitine (a compound synthesized from the two amino acids lysine and methionine) is found in high levels in red meat.  However, increased L-carnitine in the blood was only correlated with increased risk of cardiovascular disease when accompanied by high levels of TMAO, which suggests that only when bacteria that can degrade L-carnitine to TMA are present, is there an increased risk of atherosclerosis.

            The CrossFit community is not the only group increasing their protein intake.  With the popularity of the Atkins and Paleo diets, many Americans have shifted their focus from low-fat foods to consuming more protein.  Although these diets seem to help people lose weight, overconsumption of protein may result in the production of toxic compounds with detrimental effects.  After an intense workout, the body requires amino acids in order to rebuild muscle.  Therefore, the post-workout recovery shake is most likely beneficial.  However, chronic overconsumption of protein may indeed lead to an increased risk of cardiovascular and gastrointestinal diseases.  Only more research and time will tell, but until then perhaps I should only buy protein shakes formulated specifically for women.



Further Reading:

Daily Recommended Protein Intake:


http://www.cdc.gov/nutrition/everyone/basics/protein.html#How%20much%20protein

Protein metabolism/catabolism:




Gut microbiota and protein metabolism:

Russell WR et al. Colonic bacterial metabolites and human health.  2013.  Curr Opin Microbiol. 3: 246-54

Nyangale EP et al. Gut Microbial Activity, Implications for Health and Disease: The Potential Role of Metabolite Analysis. 2012. J. Proteome Res. 12: 5573-5585

Willyard C. Pathology: At the heart of the problem. 2013. Nature 493: S10-11

Koeth RA et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. 2013. Nat Med. 19: 576-585