A Donut-Only Diet Might Spare You Gout

Okay, maybe saying a diet composed of just doughnuts could save you from gout was maybe a wee bit of a stretch. But a diet composed mainly of fats accompanied by a small amount of carbohydrates actually stands a fair chance at coming to your aid. This unique regiment is known as the ketogenic diet. If you ever had a biology class in high school, you learned that glucose is the main energy source for the billions of cells in your body. Whereas that is largely the general trend, there are several instances where this doesn’t always happen. Due to the composition of the ketogenic diet, the body believes it is going through a period of starvation since there is not an abundant amount of glucose around. In response to this, the body produces a higher amount of these molecules known as ketone bodies that are used as alternative fuels for the cell. B-hydroxybutyrate (BHB) and acetoacetate (AcAc) are two of the most famous ketone bodies. In a recent paper published this February, the Goldberg et al. team examined how these ketone bodies, specifically BHB, were able to alleviate some of the symptoms of gout.

As a refresher, gout is a metabolic disorder that leads to painful inflammation of the joints and can lead to immobility if it was severe enough (“Diseases and Conditions Gout” 2017). An accumulation of small crystals in the joints are the cause of this disease (Goldberg et al. 2017). Since gout is an extreme inflammatory condition, Goldberg and her team focused on the known pro-inflammatory molecules that centered around this disease, primarily interleukin- 1b, IL-1b for short. IL-1b is responsible for causing an inflammatory response in order to protect the body during an immune response for a pathogen attack (Lopez-Castejon and Brough 2011). This pro-inflammatory goes awry in gout and leads to intense pain and fever (Goldberg et al. 2017). Another crucial aspect of gout that was investigated was the NLRP3 inflammasome. This inflammasome is composed of several different inflammatory caspases that once activated lead to an increase downstream products such as IL-1b (Baroja-Mazo et al. 2014). With a series of experiments, Goldberg et al. were able to connect how BHB was able to block the activity of the inflammasome and how ketones may be able to regulate the inflammation of gout.

One of the first things the authors did was examine how BHB interferes with the proposed gout mechanism. With an increase of the crystals in the joint, neutrophils are drawn there via an inflammasome and become activated. The authors believe to cause the pain and swelling. A deeper look into this pathway revealed that a cytoplasmic protein, found predominantly in neutrophils, are one of the activators for the inflammasome. When BHB was introduced to the situation, it was able to block this activation and in turn prevent IL-1b to be secreted and cause intense inflammation.

Now that is was noted what BHB had to contribute, it was a compelling reason why to look into how a ketogenic diet may be able to help against gout. The authors talked about how there are already IL-1b antagonists that have worked in clinical trials, but the downside was how expensive they are and the potential harmful side effects. Because of these complications, these antagonists’ uses have been extremely limited and therefore need another method which is capable of limiting the secretion of IL-1b and other pro-inflammatory agents. The authors created a biological model which gave rats gout in their knees. Following this, these rats were put on a one week ketogenic diet and had their BHB production significantly increased. The rats were examined again after the diet and were found to have their IL-1b levels and knee swelling decreased. Tissue samples from the rat subjects with gout in their knees were taken and stained to compare between rats that were on the special diet and those who were not. Those not on the diet displayed lesions and soft tissue inflammation. The samples taken from rats on the ketogenic diet revealed diminished lesion sites and inflammation. The authors concluded that the diet was able to decrease the severity of the gouty inflammation, but not alleviate it completely.

As dangerous it can be to have these joint inflammations, inflammation is a body’s natural defense to bacterial infections. The question became if these increased levels of BHB affected inflammation due to an infection. Fortunately, there was no inflammatory response change in a rat on the ketogenic diet that was infected with Staphylococcus aureus. This suggests that there is specificity for how BHB can affect inflammation.

Further experiments were conducted to further understand how BHB affects gouty inflammation. The authors found that IL-1b can be secreted in two main ways, one being of an inflammasome-dependent process and the other being an inflammasome-independent process. As stated above, BHB does interact with the inflammasome and prevent IL-1b from being secreted. But unfortunately, BHB did not appear to have any effect on the inflammasome-independent pathway.

In addition to the cellular mechanistic character of BHB, Goldberg et al. also found that BHB acted to prevent this gouty inflammation in a genetic manner as well. It was found to inhibit the phosphorylation of the DNA transcription factor NF –KB. This particular transcription factor was linked by the authors to being fundamental in the signaling event for inflammasome activation. This supports how BHB specially deals with the inflammasome to hinder gouty inflammation.

Before Goldberg et al.’s investigation, this entire mechanism was not well explored. Gout is a disease that affects 4% of the adult population with the 10% prevalence in the elderly about 60 years old. Between sequencing the human genome in 2001 and the major technological advancements made between then and now, we are capable in both prolonging someone’s lifespan as well as their quality of life. Sure, pharmaceuticals are a huge field and develop what seems like endless drugs, but that is not always the answer. Sometimes a more natural approach is more effective. This a case were there drugs that are capable of reducing gout’s inflammation, but a high monetary and health cost. By analyzing and having a better understanding of BHB’s effects on gout, a diet change might be able to be incorporated into the battle. Our bodies are capable of magnificent feats, so why not take advantage of that and let it suit us better rather than pumping endless manufactured drugs into our systems when it is not absolutely necessary.


Figure 1. This is the basic overview of how the pro-inflammatory IL-1B is produced and secreted out of the cell and produce that inflammatory response. BHB functions by inhibiting the caspase 1 cleavage and prevent a mature IL-1B from being able to be secreted.

Reference:

Baroja-Mazo, Alberto, Fatima Martín-Sánchez, Ana I. Gomez, Carlos M. Martínez, Joaquín Amores-Iniesta, Vincent Compan, Maria Barberà-Cremades, et al. 2014. “The NLRP3 Inflammasome Is Released as a Particulate Danger Signal That Amplifies the Inflammatory Response.” Nature Immunology 15 (8): 738–48. doi:10.1038/ni.2919.

“Diseases and Conditions Gout.” 2017. Accessed March 16. http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Gout.

Goldberg, Emily L., Jennifer L. Asher, Ryan D. Molony, Albert C. Shaw, Caroline J. Zeiss, Chao Wang, Ludmilla A. Morozova-Roche, Raimund I. Herzog, Akiko Iwasaki, and Vishwa Deep Dixit. 2017. “β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares.” Cell Reports 18 (9): 2077–87. doi:10.1016/j.celrep.2017.02.004.

Lopez-Castejon, Gloria, and David Brough. 2011. “Understanding the Mechanism of IL-1β Secretion.” Cytokine & Growth Factor Reviews 22 (4): 189–95. doi:10.1016/j.cytogfr.2011.10.001.

 

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One thought on “A Donut-Only Diet Might Spare You Gout

  1. Greg Sacks

    March 27, 2017 at 9:07pm

    This interrelationship is quite interesting. What I am most curious about is the origin of BHB’s capacity to inhibit certain inflammatory responses. If ketone bodies are naturally produced when the body is in a state of starvation, then there must be some correlation between inflammatory response and starvation. What is this connection? My best guess would be that it is similar to the way in which blood flow to extremities is cut off in cold temperatures – to preserve body heat for the more essential organs. In a similar manner, I wonder if during periods of starvation, the body shuts off certain inflammatory pathways as a means of conserving energy.

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    • Author

      Barry Allen

      April 1, 2017 at 9:39pm

      Hey Greg, I do like the point you bring up for examining why this occurs. Though it is likely that there is a larger picture for how BHB and inflammatory molecules have the relationship they do, but it does not appear that we know why yet. Take resveratrol for example, we talked about how this one molecule in red wine is able to activate Sirt1 and make it more effective, but we still do not know how. We can make these correlations, but still not always have the complete understanding to explain it.

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  2. Gianna Barres

    March 28, 2017 at 7:40pm

    Hi Nick!

    I appreciated that the authors tested inflammatory activity in the presence of infection because if the ketogenic diet was preventing this process, this would obviously be a problem for us. Also, it seems like a really good way to conclude that BHB’s action in preventing inflammation in gout is specific. I was also wondering if maybe we are aware of factors that make people susceptible to gout (other than age) so that we can predict a gout encounter for someone before they are in their 60’s (given its prevalence in this age group) and put them on a ketogenic diet beforehand so as to lessen the severity of the inflammation when it does ensue… interesting article!

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    • Author

      Barry Allen

      April 1, 2017 at 9:51pm

      Hey Gianna!

      That’s an excellent question! From conducting a brief search on the matter, I found there are several groups that believe there is some genetics at play that increases a person’s probability to developing gout. One research team in 2015 found that certain mutations in COMT and LRP2 loci lead to an increased risk of gout. The study was done on a Chinese population specifically so those genetic variants might be just for that one population, but there are other groups still looking.

      If you wanted to see the study for yourself, here’s the link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131302

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  3. Renan

    March 29, 2017 at 3:37pm

    I like the title. I am a big fan of homemade donuts, so I should be fine right?? I was just wondering if the diet must be altered constantly in order to minimize the severity of the inflammation? When the body is being fed on ketogenic diet, then it will get used to only having that diet and it will want more? Wouldn’t that bring future problems due to the increased amounts of ketone bodies? I guess we can just pee them out or shoot them with laser!

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    • Author

      Barry Allen

      April 1, 2017 at 10:01pm

      I see your concern, but it is my understanding that if the diet was administered as a form of treatment, it would be tailored specifically to the levels of inflammation present in the subject. I don’t see how an immunity to the diet would occur and require increasing the diet. If anything I feel there might be another factor that causes the increase in gouty inflammation and then the diet would have to be changed, but I don’t think the body would just get used to it. Does that answer your question or am I perhaps misunderstanding you?

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      • Renan

        April 27, 2017 at 10:00pm

        Yes Nick
        Thank you

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  4. Brock

    April 1, 2017 at 8:08pm

    I was interested in the fact that the authors mentioned that a ketogenic diet can induce dyslipidemia in gout patients. This made me immediately think about how ketone bodies are related to lipid metabolism. Considering this, I now wonder how PUFA metabolism might play a role in gout. PUFAs can also have anti-inflammatory effects, so maybe both BHB and some PUFAs could play roles in mediating inflammation in gout? I think this just goes to show how interconnected our metabolism truly might be.

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    • Author

      Barry Allen

      April 3, 2017 at 5:43pm

      Brock that is such a great thought that I never would have considered. Depending on the clearance of the fats ingested/lipid metabolism, it is very plausible that dyslipidemia can occur. But ushering in another anti-inflammatory source such as PUFAs and create this inflammatory cocktail effect might prove to be just as effective and perhaps more healthy. We could just have to remember that it’s the omega-3’s we want.
      The only thing to note is the source of the omega-3s. Part of the ketogenic diet is to have only so much protein compared to fat so the omega-3 source would have to adhere to that regiment or that might affect the BHB production that is playing such a vital role.

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  5. Abby Lazofsky

    April 21, 2017 at 12:00pm

    I was wondering if there would be a difference in how these fats interacted with the body based on what kind of fat was mostly being consumed? By this, I mean fat intake from an avocado is generally thought to be more healthy than fat intake from a doughnut.

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  6. Beth Garrison

    April 28, 2017 at 8:27pm

    Very interesting article! There are so many ways that our diet affects our bodies, and I never would have thought that it significantly impacted a disorder like gout. I was wondering if you had any insight as to how the inflammatory response is specific to certain types of inflammation. What is unique about gout inflammation that allows BHB to interfere with it but not others?

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  7. Katy Mayer

    May 5, 2017 at 6:32pm

    Hi Nick! I think this was a really spotlight! Knowing more about gout now and how it can be caused by purine catabolism, I find this study particularly interesting. I can see how combining a low purine diet with a ketone diet can be especially beneficial to patients suffering from these horrendous symptoms. I would be interested to know how just limiting purine consumption would affect the inflammasome. Thanks for your post!

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  8. Lena Ogiwara

    May 5, 2017 at 6:36pm

    Hi Nick
    I think studies looking at diet are particularly “hot” right now as far as treating and preventing different diseases. My personal interests deal more with dietary impacts on gut microbiota, but many of these spotlight blogs have addressed how diet may impact the development of different diseases. I think the authors make a fair point at the end, when they address that KD are hard to adhere to and may have side effects in gout patients. They suggest ketone esters as an alternative way to increase BHB, which I found interesting because although their findings suggest KD is the way to go, the idea of ketone ester supplementation makes their findings more reasonable as far as actual implementation as a treatment. Thanks for sharing!

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  9. Aisha Kourouma

    May 6, 2017 at 12:33pm

    Hi Nick! This was a very interesting article, and you made it very easy to follow through the experiments. It looks like diets are becoming pretty fashionable in the field. Considering a ketogenic diet can lead to dyslipidemia in patients with gout, I was wondering how PUFA may play a role in the disease since it has anti-inflammatory effects. Also, how is gout different from other types of inflammation in that its susceptible to only BHB?

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