The placebo effect

This is a topic I want to explore in more detail in the future, but for the time being, I’d like to share the following links:

Personally, I  believe that the placebo-effect is more relevant when it comes to non-prescription based approaches to treating RA.  However, I’m willing to let my brain trick me, as long as I feel better! Thus, I’m going to continue to avoid aspartame, even if there’s little evidence that it helps with RA.



The evil of sweetness! (Part 1)

I believe that every patient with severe RA would give up almost any food product – if it effectively treated their RA!  I’ve tried multiple “anti-inflammatory” diets, with some limited success.  I’m gluten-free because of Celiac disease, but do notice that my RA flares up if I accidentally eat gluten.  Through observation and trial-and-error, I’ve noticed that any more than a few bites of red meat gives me problems the next day. The smallest and easiest diet change I made had the biggest effect on my pain level.  A few years ago I read a news report on aspartame that stated aspartame magnified pain signals in those with chronic pain because it acted as a neurotransmitter.   Unfortunately, I was unable to find this site again, but the neurotransmitter hypothesis was enough motivation for me to eliminate aspartame from my diet.  After four days of no-diet-soda or sugar-free gum, my pain intensity decreased by at least 50%!  My goal in this series of posts is to review the scientific basis of eliminating aspartame to decrease pain and help others decide whether going aspartame-free is worth a try. This post covers some of the preliminary case studies on aspartame and pain and diverges a little to discuss the potential cancer risk associated with aspartame.

Aspartame, marketed as NutraSweet, is the most common artificial sweetener used in diet products.  Chemically, it consists of two naturally-existing amino acids (aspartic acid and phenylalanine) joined by a peptide bond.  Amino acids are naturally linked through peptide bonds to form proteins.  While dipeptides do naturally occur, aspartame is artificial and synthesized through chemical and/or enzymatic reactions.  Aspartame is currently used in over 5,000 products (and almost every commercially-produced gum)!

First, let’s look at anecdotal evidence. In 2010, two chronic pain patients were able to go into complete remission by solely eliminating aspartame from their diets (Ciappunnci et al. 2010).  The first patient, a 50-year old woman with fibromylagia noticed remission of symptoms when traveling abroad and, with her doctor, was able to connect it to consumption of aspartame.  However, a search on PubMed (the database for published research articles focusing on medicine) didn’t yield any similar case studies for rheumatoid arthritis.  Additionally, while case studies are valuable in identifying new approaches to research or treat diseases, they do not “prove” the effectiveness of a treatment – what works for one person may not work for someone else.  With that in mind, let’s collect some of our own data.  Once you answer the survey, you’ll be able to see how everyone else has responded.

This is a live poll, but after the first set of results, I discovered that my experience with aspartame may be in the minority.  My doctor has mentioned that I might also have fibromyalgia, so that could explain why I saw a benefit and others with RA haven’t.

So why would eliminating aspartame benefit fibro patients, but not RA patients? I’m researching this to address in Part 2 of this post, but first (in my never-ending quest to get my husband to eat healthier), a slight tangent.

Aside from RA, are other reasons to avoid aspartame justified by scientific studies? A link between cancer and aspartame is frequently cited as a reason to avoid diet soda.  There are three major approaches to determining the potential for chemicals to cause cancer:

Summarized from Yismal and Ucar, 2014.

Summarized from Yismal and Ucar, 2014.

  1. Genotoxicity studies, which study the direct impacts of chemicals on DNA structure in individual cells (from bacteria or mammals)
  2. Carcinogencity studies, which compare the incidence of  cancer in test animals that receive high doses of the chemical to those that aren’t treated with the chemicals
  3. Epidemological studies, which survey people on their use of chemicals and track whether or not they get cancer.

A recent review found that the majority of research studies have found a link between aspartame and cancer, as summarized in Figure 1 (Yilmaz and Ucar, 2014). One common criticism of genotoxicity and carcinogenicity studies is the mega-doses of chemicals to which the animals are exposed. The FDA has set the acceptable daily intake (ADI) of aspartame at 50 mg per kg of body weight; in other words, a 165-lb person would have to drink 19 diet cokes each day to have a noticeable increase in cancer risk (American Cancer Society).   In the reviewed genotoxicity studies, cells were exposed to 3.5 – 1,000 mg of aspartame per kg of body weight (or 1.3 – 380 diet cokes).  Only two of the studies found evidence of genetic abherrations (or potential for cancer) at doses of aspartame less than the ADI; in contrast, six studies found no risk even at much higher doses.  In the animal studies, the minimum dose documented to cause an increased risk of cancer was 8 times the ADI (or 152 diet sodas per day for a 165-lb person).

A epidemiological study that was completed in 2012 reignited the controversy over whether aspartame is linked to cancer.  NPR ran an excellent story on it that I use to help teach students statistics because it explains what is meant by statistical significance.

In statistics, saying something has a “significant” effect has to do with your confidence that your results were due to what you were researching and not chance. Researchers have a very high bar for significance, typically accepting less than a 5% or 1% probability that what their observed results were due to chance. Personally, since I wasn’t addicted to Diet Coke and didn’t see a downside to not consuming aspartame, I was willing to accept a higher probability than 5%.  It’s also important to distinguish between “significant” and “substantial” effects when talking to researchers.  Significance deals with whether the effect truly exists; substance has to do with how large the effect is.

For this study (Schernhammer et al. 2012), the controversy arose because many of the relationships between cancer risk and aspartame had significance values greater than 5%.  Additionally, the effects were practically small. For example, the the risk of developing multiple myeloma by men drinking at least one diet soda per day doubled, from 0.6% to 1.2%., with a significance value of around 6%.  This was the largest effect that was observed, and, surprisingly, a similar effect was observed for men drinking that much non-diet soda.  Another large criticism of the study is that the observed increase in cancer risk was not observed overall, but only when specific trends were considered.  Continuing the same example, there was no increased risk of multiple myeloma from drinking diet soda for women.  Consequently, I leave it up to you to decide whether to eliminate aspartame from your diet due to any potential cancer risk.

Research articles reviewed:

  1. Ciappuccini R, Ansemant T, Maillefert JF, Tavernier C, Ornetti P. Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain. Clin Exp Rheumatol. 2010 Nov-Dec;28(6 Suppl 63):S131-3. [Pubmed link]
  2. Yilmaz, S and Ucar, A.  A review of the genotoxic and carcinogenic effects of aspartame.  Cytotech.  2014; 66: 875 – 881. [Pubmed link]
  3. Schernhammer, ES, Bertrand KA, Birmann, BM, Sampson L, Willett, WC, and Feskanich, D.  Consumption of artificial sweetner and sugar containing soda a d risk of lymphoma and leukemia in men and women.  Am J Clin Nutr. 2102; 96(6): 1419-28. [Pubmed link]