Butyrate Series, Part 7

Introduction:

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
resistant starch.

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.

http://www.amazon.com/BodyBio-E-Lyte-Butyrate-600-caps/dp/B0016NHCGA/ref=pd_sbs_hpc_1

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!

http://www.bodybio.com/main/products/sodiumbutyrate_qa.htm

http://www.amazon.com/BodyBio-E-Lyte-Sodium-Butyrate-caps/dp/B0058A9SF0/ref=pd_sbs_hpc_2

BodyBio/E-Lyte 500 mg (Sodium-Potassium Butyrate): One review regarding autism.

http://www.amazon.com/BodyBio-E-Lyte-Sodium-Potassium-Butyrate-Capsules/dp/B0058A9SRI/ref=pd_sim_hpc_2

Pharmax, Butyrate Complex: Three reviews. Constipation, yeast, and a nothing.

http://www.amazon.com/Pharmax-Butyrate-Complex-90-vcaps/dp/B0037V3WTA/ref=pd_sbs_hpc_3

Nutricology/ Allergy Research Group ButyrAid: 5 reviews. IBS, dysbiosis.

http://www.amazon.com/Nutricology-Butyraid-Tablets-100-Count/dp/B0014TDVXE/ref=pd_sbs_hpc_4

Cal-Mag Butyrate: 1 review. Leaky gut.

http://www.amazon.com/Ecological-Formulas-Cal-Mag-Butyrate-Capsules/dp/B003TV99EA/ref=pd_sbs_hpc_5

T.E.Neesby – Butyrex Cal/Mag, 600 mg, Micro encapsulated design: Two reviews. GI related and insomnia.

http://www.amazon.com/T-E-Neesby-Butyrex-Cal-Mag-capsules/dp/B00014G70C/ref=pd_sbs_hpc_9

http://www.jigsawhealth.com/supplements/butyrex

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.

http://www.amazon.com/Allergy-Research-Nutricology-Butyren-tablets/dp/B00014FOCY/ref=pd_sbs_hpc_11

BioCare Butyric acid complex (magnesium and calcium): No reviews.

http://www.biocare.co.uk/default.aspx?GroupGuid=29&ProductGuid=11890

Digestix: Two fair reviews.

http://www.pinnaclebio.com/products/digestix-%E2%80%93-calcium/magnesium-butyrate/

Forms of butyrate not available over the counter, per se:

Tributyrin:

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:

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)

Butyrylated Starch:

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.)

Enemas:

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.

Conclusion:

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.

http://catalyticlongevity.org/

http://catalyticlongevity.org/prepub_archive/Tributyrin-AD.pdf

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

6.  http://en.wikipedia.org/wiki/Butyrin

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.

31 thoughts on “Butyrate Series, Part 7

  1. Natalia Holcomb

    Once again, thank you! I started supplementing potato starch twice a day and two capsules of the first butyrate product that you linked to in late November or early December. It’s made a big difference on my bowel regularity. It’s making it a lot easier to see what foods are affecting me poorly. I think probiotics will be the final link in that chain.

    Reply
    1. thehomeschoolingdoctor Post author

      Your story sounds like mine on butyrate/resistant starch (RS)! Crazy difference, eh? For the first six-seven weeks of pregnancy, I was able to keep up the green bananas and potato starch, adding in some white beans here and there. Things were great, despite stopping butyrate when I discovered pregnancy. Then, I got too sick to even think about potato starch, beans, green bananas, cold potatoes, all of it–and things have been sadly been backsliding, no urge at all this week. It will be interesting as I get feeling better and able to add those back in to see if I can get back where I was.

      I’m looking forward to putting together the information on probiotics which increase butyrate, either directly or indirectly. I regret to say I know it will take awhile until I feel better.

      All the best to you and those you love. May 2014 bring you health, inner peace, and strength.

      Reply
  2. Nishka

    Thank you! I so look forward to these 🙂 Great information. The butyrate complex I’m taking was really starting to kick in and help me until I got a sinus/ear infection I couldn’t kick and started taking amoxicillin…everything came to a halt. Only a couple more days left of the antibiotic and I’m hoping things start moving again. And hang in there Mama, I can vividly remember those days and how tired I was…hoping you are doing well and things are moving along. Happy New Year!

    Reply
    1. thehomeschoolingdoctor Post author

      Interesting to hear an empirical report that the butyrate was helping! Sorry to hear about the ear infection requiring amoxicillin– which did a number on your natural helpful bacterial flora. That is beyond frustrating. But that’s just the way it is! We move onward despite hurdles. No challenge is too great after we regroup. (Smile. Pardon my hyperbole. The words are probably really meant for me, as I feel so yucky still. Isn’t that fatigue just about the worst?) I have read that it takes about a month to restore flora after an antibiotic. So be patient as you do the right things. Happy New Year to you, also! May it be blessed!

      Reply
  3. Tricia

    Good to hear from you! So do you think butyrate should be taken as a supplement long term? Been taken it and wondering if I should continue to as part of my daily supplement protocol. Hope your feeling great! Tricia

    Reply
    1. thehomeschoolingdoctor Post author

      Hi there! So does that mean you may have found some beneficial effect from it, then? How exciting, if so! Nothing I have read so far has put up any flags for me regarding this supplement, other than making sure the dose isn’t outside of recommended and making sure the manufacturer seems reliable. I have heard that naturopaths and chiropractors use it, and I wish I could pick their brains on their experiences with it. How long do they keep patients on it? What kind of issues do they use it for? After reading the EPA report I mentioned, it seems pretty non-toxic, but I never have seen anything with long-term studies, so how can anyone say for sure? Personally, my tactic was going to be to use it as I titrated up the potato starch and green bananas for resistant starch (RS), occasionally coming off of it long enough to see if RS was going to cut it. I have to say, it was going pretty well, until I got too sick to stomach putting most things in my mouth, especially potato starch and green bananas! (Smile) Once I get to feeling better, I’ll try going back to RS. Hopefully soon I’ll be feeling back to my old self.

      Reply
  4. The Vanilla Housewife

    So so hard to eliminate processed foods! Eating healthy in this part of the world is too expensive!
    Wait, did I read it right? You’re expecting? That is good news Terri! How did I miss that? Congratulations! Great things in store for you this year!

    Reply
    1. thehomeschoolingdoctor Post author

      I’m sorry it is too expensive. It doesn’t seem fair. It seems with that climate in the Philippines that fruits, vegetables, and fish would be a dime a dozen. But, yes, even here–it is MUCH cheaper to buy boxes and cans devoid of vitamin C, vitamin B 12, vitamin B6, and so on. I know that is why it is so hard to transition. I feel they have snagged us in and keep perpetuating the cycle. But there has to be better choices–even if there are not ideal choices? Yes? No? Tell me. After seeing the health differences in my family, I just want to make it do-able. The Philippines probably isn’t like the USA in health–I don’t know I haven’t read statistics, but here, obesity reigns. From kindergarten to grandparenthood. Immune diseases are skyrocketing. Depression and anxiety. GI distress issues. Allergies. I’m convinced our food choices are a HUGE chunk (not the only chunk) of the escalation of those issues. Any little part I play in helping others gain more veggies/fruits/less processed oil and fats/less reliance on processed grains, etc, makes me feel better. The better we feel, the better we can help others and ourselves.

      [Yes, you read right. It is early (and I know the statistics). But if all goes well, I’ll feel better soon and have a new little one in August. You missed it because I’ve felt so horrible all I’ve been able to write is sarcastic comments on other blogs 🙂 .]

      Reply
      1. The Vanilla Housewife

        We have health issues here too, and published statistics wont even help anybody understand how widespread the problem is because many do not look for medical help. A lot of us self-medicate and rely on herbal stuff. Although we do have top notch medical facilities available and it’s not like how it was many years ago but the chances of an average Filipino seeking professional help is slim mostly because of cost. Depression and anxiety is not something that we seek help for. We don’t go to psychiatrists and by we, I mean those that are not part of the upper socio-eco class, which makes up the majority of the country. Diabetes and Hypertension is something I know that is common here. Vegetables and fruits can be inexpensive but the organic ones are not. It is much cheaper to buy canned goods and instant noodles than to cook meals at home. Allergies to food, although present is something that’s really not a major issue here (I think), I’ve read about American kids allergic to so many things. I guess the health problems that we have may be similar to the issues in the US or it could be worse because many don’t seek help and are not included in the statistics.

        But why are we dwelling on these things right now, we should be celebrating your good news! I am so happy for you! Although I feel for you because I felt horrible during the first trimester of my pregnancy with the little girl, all I did was puke and cry and had to be on medical leave for sooo many health issues.

        Congratulations Terri! I hope your body adjusts to the hormonal changes soon so you can feel better!

      2. thehomeschoolingdoctor Post author

        Yep. Those last two paragraphs about sum it up. I wonder how I ever worked through pregnancy!!

        I’ll leave it all at that and mull internally over your insight on the Philippines issues as I continue to blog and try to encourage. I’m going to log off now. Hugs.

  5. All Seasons Cyclist

    Since I started following a Paleo diet I have come to enjoy real butter without guilt (awesome). However, we use coconut oil as our primary fat. Do you know if coconut oil is a butyrate-containing or producing food? Also, I think I’ll stay away from the carp bait (I’ve been away from Indiana too long).

    Reply
    1. thehomeschoolingdoctor Post author

      I know what you mean about butter. The more I learn about it and other foods, just all the more fascinating it all becomes! Coconut oil is probably a good choice, I’d think, with my preliminary readings on Alzheimer’s/dementia. I will read more on it eventually and post. Coconut oil is full of beta-hydroxy-butyrate. How that fits into butyrate is left for me to unravel hopefully later this year or two (I try to be realistic in my expectations 🙂 ).

      That would be some really smelly carp bait! Indiana rocks! It will always be home for me, even as I tarry onward.

      Reply
  6. andthreetogo

    Again, another post where you take something that could be so confusing and make it easy to read!
    ANNND… congratulations! I also was a very unhappy pregnant person in my first trimester. The second was great and then the third, well it was a day to day mix of emotions. 🙂 I cannot imagine being pregnant and taking care of my toddler though, so the fact that you are taking care of and homeschooling your other children, writing this blog, and also pregnant… wow, you rock! Happy New Year!

    Reply
    1. thehomeschoolingdoctor Post author

      Glad it was understandable! Just don’t ask me to explain physics. I’ve always hated physics. 🙂
      Thanks for the wishes and comments which help me feel better. A good husband truly makes everything possible. (Isn’t that right?) So your first few months were rough, eh? Me, too. Every time.

      Reply
      1. andthreetogo

        A good husband does make a huge difference. Chad kept me sane in my emotional chaos. Yeah, I was really sick all the time. It was pretty horrible. But then at 16 weeks that gave way to feeling great.

  7. IrishMum

    Congrats on the great news!!

    So much to read, I am going to have to come back tomorrow and reread. My brain is too tired to absorb it now, but I will say that I was a little disappointed that there were no “bubble-gum” photos 😉

    Reply
  8. Pingback: Anxiety, depression, laziness...Can the nameless wonder change? - Page 586 | Mark's Daily Apple Health and Fitness Forum page 586

  9. myjourneythrume

    It is 7.30am here as I’m reading this post and my brain isn’t quite working yet so I’m going to have to reread this when I’m more awake! But it’s such a good helpful post Terri, thank you for sharing it all. I think I need to investigate butyrate, it sounds like it could help me. Green bananas make me bloat almost instantly. Interesting to hear about the effects of pregnancy on your ‘system’ I’ve wondered what would happen to mine if I were pregnant. Huge congrats on the baby news, I love how you subtlety slipped it into the post 😉

    Reply
    1. thehomeschoolingdoctor Post author

      Thanks, Jess. No worries about butyrate; all of us could get it through diet with a few nips and tucks, I believe–green bananas or no! I don’t mind parenthood one little bit, but pregnancy and I hate to tangle. Just want to slap those women who say, “Oh, it’s the best I ever felt.” Don’t know whether to believe them or think they’re fools. (Sorry for the sarcasm. Still not feeling well.) But, honestly, I do know EVERY person’s body is COMPLTETELY different, and I don’t think one can tell how it’ll treat them–even from pregnancy to pregnancy. Mine has been quite reliably miserable every time.

      On all that negativity, ha ha!, have a wonderful week over there! Life really is good!

      Reply

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