We have made it to butyrate supplements.
Diet-wise, I follow the GAPS diet with modifications resembling a Paleo Diet/Autoimmune Paleo Diet –with some low carb stints thrown in to try to achieve my health goals. I don’t have any lofty goals of looking like a runway model or movie star. I’m still a little young to be much scared about cancer. I don’t hang out with a fitness crowd to bring out my competitive inner edge. My labs and ideal body weight have always checked out ideal.
I started the GAPS diet for exceptionally severe, idiopathic constipation and tweaked it here and there based on my research. The symptoms I have changed include headaches, chronic allergy symptoms, fatigue, dry eyes, strange premature hot flashes, and I could go on. My gut improved, but I still thought it could work better. Several months ago, I started following some leads on nerve regeneration in the gut, and they lead me to butyrate. I decided I would try an oral butyrate supplement, despite the researchers all saying a delayed release product was probably necessary. If, by some chance, oral butyrate helped me, I would then focus on tweaking my diet some more to obtain butyrate naturally through food. I was amazed when oral butyrate worked for me, particularly as I didn’t even choose a sustained release formulation. If I stopped butyrate, my symptoms returned. When I resumed it, my symptoms resolved. So I’ve been working to try to increase forms of fiber and resistant starch that I tolerate–I’ve defined these in previous butyrate posts.
Ways I see to increase butyrate:
1. Eat foods with butyrate (butyrate-containing foods), like high fat dairy products such as butter. (Part 4)
2. Eat foods that your bacteria can make butyrate from (butyrate-producing foods), like fiber and
3. Take butyrate supplements.
4. Take butyrate producing probiotics and prebiotics.
A bit about butyrate production.
Aside from the pharmaceutical industry, butyric acid is also used in the manufacture of plastics, varnishes, disinfectants, perfumes, and cosmetics. (Butyric acid and butyrate are interchangeable terms for our conversation.) The American Food and Drug Administration has even approved it as an additive to food, beverages, and flavorings in the form of tributyrin. (1) You’ll see more on tributyrin below. (Humorous: I also found it is used in fish bait: Carp Fishing Pellets. Nice.)
The organic structure of butyrate is simple. It is just four connected carbons saturated with hydrogens with a carboxylic acid on the end of the chain. The manufacture of butyric acid is mainly from chemical synthesis using crude oil extracts. Crude oil extracts provide cheap, readily available ingredients. Butyrate can be extracted from butter, but the process is reportedly more difficult and expensive. Another way to obtain butyrate is through bacterial fermentation (the way we naturally get it from resistant starch and fiber in our colons). Bacteria are given the appropriate matter, and they ferment it to make butyrate. The fermentation method interests manufacturers because of the growing interest in “natural” sources for foodstuff. (1) Butyric acid itself is a bit corrosive, and in supplements it will be found as a salt form.
My concerns with oral butyrate supplementation–and supplements in general.
My concerns with oral butyrate supplements are not unique to butyrate; they are the same concerns I have with supplements in general. Butyrate seems to have a pretty good track record. I mean, as I mentioned above, it’s even approved by the FDA for flavorings. But any time I take a supplement I ask myself a battery of questions. Could there be impurities, such as heavy metals? What is the proper dose? Does the supplement contain the amount of active ingredient it says it does? What if people take enormous amounts? Should there be a concern with unopposed supplementation? (What I am thinking of here pertains to “ratios.” For example the ideal ratio of calcium to magnesium supplementation. Or the ideal omega-3 to omega-6 ratio.) What are the side effects?
Butyrate seems pretty non-toxic as long as the manufacturer’s dosing guidelines are adhered to. One study found that escalating doses in mice lead to kidney swelling– in humans the equivalent dose would be 7-8 grams in humans. (2, 3) To put it into perspective, the butyrate supplement I tried recommends a dose of up to 3.6 grams. Another study specifically points out that in vitro, butyrate has positive effects until a certain point at which it has an opposite, detrimental effect:
“We conclude that the effect of butyrate on the intestinal barrier is paradoxical; i.e. whereas low concentrations of butyrate may be beneficial in promoting intestinal barrier function, excessive butyrate may induce severe intestinal epithelial cell apoptosis and disrupt intestinal barrier.” (4)
And finally, here is a nice toxicology report on butyric acid from the Environmental Protection Agency, “Screening Information Data Sets” (SIDS). The report was accumulated for the SIDS Initial Assessment Meeting, referred to as the SIAM, in 2003. It goes over just about anything you’d want to know about butyric acid, from its different uses to its stability in water to its effects on rats and their fetuses. For those interested in the toxicity profile as it at least relates to rats, scroll down a ways. It will talk about effects on male rats, female rats, pregnant rats, developing fetuses, chromosomes, etc. (5)
What are some commonly available butyrate supplements?
I Googled some supplements, and I will list those that I found. By listing them, I am not recommending any of them! (Neither am I dis-recommending any of them.) I’m simply listing in one spot just about all the supplements I could find and available consumer reviews. If you think butyrate may be right for you, run it by your favorite healthcare provider. Maybe print off a couple of the studies I’ve linked to in my article and the EPA report above to help the provider understand toxicity, perhaps highlighting the sentences of interest to facilitate quick reading for them. I’m not in the situation to recommend anything, but I am happy to share my own personal experiences and research that I’ve come across.
Keep in mind the success of butyrate supplementation is going to vary from person to person. The pills will release their contents differently because of inter-individual differences in the pH of a person’s gut and transit time. These supplements are salts, and the butyrate provided by these supplements will probably be absorbed very early in the GI tract, perhaps offering no benefit. There are other forms of butyrate used out there but not over the counter. I will mention them later.
P.S.: Thank Amazon for the photos. I didn’t realize the links came with photos. Well, that saves you from my very bad drawings and “bubble-gum” photos. (Sorry. “Bubble-bum” is the word my dad used to describe the music I listened to as a kid.) Rest assured this is still a hobby; I make no money from it.
• BodyBio/E-Lyte Butyrate 600 mg (Calcium/magnesium complex): This one has five reviews you can read on Amazon. The reviews revolve around fibromyalgia, collagenous colitis, excess ammonia, and multiple food sensitivities.
• BodyBio/E-Lyte 600 mg (Sodium Butyrate): This one also has five reviews on Amazon, around cancer, bipolar, substance addiction, and more nebulous issues. Quite interestingly enough, this also has medium chain triglycerides in it!
• BodyBio/E-Lyte 500 mg (Sodium-Potassium Butyrate): One review regarding autism.
• Pharmax, Butyrate Complex: Three reviews. Constipation, yeast, and a nothing.
• Nutricology/ Allergy Research Group ButyrAid: 5 reviews. IBS, dysbiosis.
• Cal-Mag Butyrate: 1 review. Leaky gut.
• T.E.Neesby – Butyrex Cal/Mag, 600 mg, Micro encapsulated design: Two reviews. GI related and insomnia.
• Butyren, Allergy Research (Nutricology): “ButyrEn, from Allergy Research Group, is an enteric-coated tablet of the calcium and magnesium salts of butyric acid, providing 815 mg of butyrate and 100 mg of both calcium and magnesium…the enteric coating is designed to provide delayed release in the intestinal tract.” Two reviews which don’t offer much.
• BioCare Butyric acid complex (magnesium and calcium): No reviews.
• Digestix: Two fair reviews.
Forms of butyrate not available over the counter, per se:
In many butyrate research studies, tributyrin is used. Isn’t it fascinating that it is tributyrin which naturally occurs in butter? (6) Tributyrin serves as a delayed-release source of butyrate, and hence achieves more sustained plasma levels. It is made of a glycerol backbone with three butyrate molecules attached. However, even still, it is absorbed before the colon:
“Oral tributyrin (glycerol tributyrate) is absorbed in the small intestine and at high doses increases free butyrate concentration in peripheral plasma for up to 4 h. However, the hepatic uptake of intestinal butyrate is known to be almost complete, suggesting that systemic delivery of butyrate to the colon would be limited.” (7)
Tributyrin has been used in many studies including, but in no way limited to, cancer studies, metabolic studies, and neurological disease studies. Oncologists were hopeful that it could achieve the cancer-slowing benefits in vivo as is seen with butyrate in vitro; about 20% of cancer patients achieved long-term disease stabilization when receiving 200 mg/kg 3 times daily in a pilot trial. In diabetes and obesity, reports suggest tributyrin has the ability to suppress the induction of obesity and insulin resistance in mice fed a high-fat diet. Researchers speculate there may be an impact of tributyrin on the cognitive function of patients with early Alzheimer’s disease, although they express concerns:
“From the standpoint of practicality, however, it would be necessary to incorporate tributyrin into a functional food, as it would not be feasible to require the ingestion of many dozens of capsules daily.” (3)
Phenylbutyrate is an “orphan” drug used in rare conditions. What in the heck is an orphan drug? An orphan drug is one that has been pushed through the typical drug approval process usually because the disease it treats is so rare. Phenylbutyrate has activity similar to butyrate (induction of apoptosis and histone acetylation) and is used for urea cycle disorders. I have listed it here as its actions seem similar to butyrate, and if one is exploring butyrate, they can also pursue study of phenylbutyrate. (8)
Some studies have started using high amylase corn starch with butyrate attached. You’ve seen high amylase corn starch mentioned in this series before when I discussed resistant starch. (7, 9) Potentially, they’d like to consider adding butyrylated starches to food products to promote health. (Darn it, folks. Why do we keep letting ourselves be manipulated this way? Instead of a cheap study looking at the safety or toxicity of raw potato to deliver resistant starch to the colon to bolster butyrate production and butyrate promoting bacteria, they’re coming up with more ways to modify your food source. Why can’t we get it together? When is enough enough? Stop eating processed foods. Even gluten-free ones.)
These may be helpful in ulcerative colitis. Research results are mixed. The one formulation I found pre-prepared had been discontinued. I read some forums, but I couldn’t really find any strong leads here. It seems that to get these, you have to take your prescription to a pharmacy which compounds (makes) them specially for you. The smell and delivery mechanism are undesirable I read–not to mention the exposure time of the colon epithelium to butyrate will be brief. If you have anything to leave in the comments regarding these, some Googlers may find it helpful in the future.
Thanks for reading. I’m sorry this has taken so long to prepare. I hate that I pretty much came to a halt on a series. I’m in my first trimester of pregnancy. I’m not a very pleasant pregnant person. Give me a baby. Give me a kid. Don’t give me pregnancy or a toddler. (Joke.)
The next Butryate Series post will revolve around using probiotics to increase butyrate in the gut. But I may have to write some “bubble-gum” posts in the meantime, if I can even type up anything at all. I’m about shot. Please point out typos and mis-information, please. I appreciate it. ~~Terri
Sources: There are some interesting sources today. Read and scrutinize carefully.
1. Acetate adaptation of clostridia tyrobutyricum for improved fermentation production of butyrate. Adam M Jaros, Ulrika Rova and Kris A Berglund. 2013. SpringerPlus 2013, 2:47. http://www.springerplus.com/content/2/1/47
2. Minamiyama M, Katsuno M, Adachi H et al. Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum Mol Genet 2004 June 1;13(11):1183-92. http://hmg.oxfordjournals.org/content/13/11/1183.long
3. Tributyrin May Have Practical Potential for Improving Cognition in Early Alzheimer’s Disease Via Inhibition of HDAC2. Mark F. McCarty. March 2013. Catalytic Longevity.
4. Effects of Butyrate on Intestinal Barrier Function in a Caco-2 Cell Monolayer Model of Intestinal Barrier. Peng, He, Chen, Holzman, and Lin. Pediatric Research (2007) 61, 37–41. http://www.nature.com/pr/journal/v61/n1/full/pr20079a.html
5. SIDS Initial Assessment Report. For 16th SIAM. May, 2003. http://www.epa.gov/hpvis/hazchar/Category_ButylSeriesMetabolic_HC_SIAR_0108_Interim.pdf
7. Butyrate delivered by butyrylated starch increases distal colonic epithelial apoptosis in carcinogen-treated rats. Clark et al. Carcinogenesis. 2012 January; 33(1): 197–202. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276328/
8. A Phase I Clinical and Pharmacological Evaluation of Sodium Phenylbutyrate on an 120-h Infusion Schedule. Carducci, Gilbert, et al. Clin Cancer Res. October 2001. 7;3047. http://clincancerres.aacrjournals.org/content/7/10/3047.full
9. Butyrylated starch increases colonic butyrate concentration but has limited effects on immunity in healthy physically active individuals. West et al. 2013. EIR. 102-119.
- Butyrate Series, Part 5 (thehomeschoolingdoctor.com)
- Butyrate Series, Part 6 (thehomeschoolingdoctor.com)
- Butyrate Series, Part 4 (thehomeschoolingdoctor.com)
- Butyrate Series, Part 2 (thehomeschoolingdoctor.com)
- Butyrate Series, Part 3 (thehomeschoolingdoctor.com)
- Butyrate Series, Part 1 (thehomeschoolingdoctor.com)