Because I know how to have fun, I have spent hours and hours over the last 2 days reading about d- lactate acidosis. I’m not even sure why. It was one of those things, I guess, that suddenly struck me as interesting – and I felt I needed to understand it better.
It turns out that for those of you wrestling with IBD, autism, or chronic fatigue, you’ll want to know all about d-lactate acidosis too! (A warning in advance. This is a long and somewhat convoluted blog post. I got a little overly enthusiastic about sharing!)
First, let me start with the basics:
Bacteria eat sugar. Remember that all carbohydrates (di-saccharides, like table sugar and the lactose found in dairy, and starches (long strings of sugar molecules)) are eventually broken down to single molecules (simple sugars) before being absorbed into the blood through cells in the intestine. In cases where digestion or absorption of carbohydrates is faulty, these carbs may remain in the intestines, leaving way too much food lying around for gut bacteria…giving them plenty of energy to reproduce, potentially leading to SIBO (small intestine bacterial overgrowth).
When bacteria “eat” sugar (ie. ferment), they release a variety of byproducts. Some species, like Lactobacillus, release lactic acid, of which there are two kinds: L-lactate and D-lactate, which are isomers – that is, they are mirror images of each other. L-lactate is easily metabolized. D-lactate, however, which normally should be produced only in minute amounts, is slow to be metabolized.[i]
In those with short bowel syndrome (wherein the small intestine needs to be re-sectioned for whatever reason (bowel disease, obstructions, etc.)) – who then have less surface area in the gut to digest and absorb – there is often an overabundance of undigested carbohydrates. But poor digestion is a factor in other illnesses as well, like the inflammatory bowel disease, Crohn’s.[ii] And autism: we not only know that the kids have dysbiosis: we also know that they have poor digestion and absorption of carbohydrates.[iii] Once there is an overgrowth of bacteria in the intestines, it becomes a vicious cycle: bacteria produce acids (like lactic acid), and the ensuing lower pH from these acids makes a more hospitable environment for bacteria, many of them lactic-acid producing. Once you have an overgrowth, you have a more-than-normal production of d-lactate…and as I just said, it is metabolized slowly, so it builds up.
This un-metabolized d-lactate easily passes from the gut to the blood to the spinal fluid and brain, and is highly neurotoxic. In fact, this state, d-lactic acidosis, is characterized by a variety of neurological symptoms including slurred speech, ataxia (loss of control of body movements), balance issues, altered mental states, psychosis and if bad enough, even death. Patients often appear drunk. In one paper I read, other symptoms are listed including lethargy, echolalia (meaningless repetition of words), confusion, nausea, weakness, explosive speech.[iv]
So to sum up so far: in those with SIBO, the overgrowth of gut bacteria, even “good species,” leads to higher than normal levels of bacterial byproducts, including lactate. Since d-lactate is metabolized slowly (unlike it’s L- counterpart), it can build up to toxic levels and in susceptible individuals, cause neurological symptoms.
Well, this was all very interesting to me, especially as one of the most common symptoms I have seen in kids with autism, who tend to be enormous carb eaters (they seem to crave them), is “drunkenness” upon eating. My own son was no exception: I have a clear memory of calling Alex’s doctor when he was 3 after a visit to the zoo in Central Park, in New York City. Alex had eaten a bagel and had a cup of grape juice, and was sitting in his stroller abnormally giggling like he was absolutely loaded. I got him up to look at polar bear, and he couldn’t even walk – just fell over like a drunkard. More than that: for the last 15 years, I have commented (including in my January 1, 2017 blog post here) that with Alex’s first meal on the Specific Carbohydrate Diet (just a steak as I had no idea what I was doing yet!), he stopped vomiting. The nausea vanished with the first meal.
Ok – now a little tangent:
It was when I got to this sentence in the first paper I read that my world tipped slightly sideways: “Thiamine deficiency has been associated with lactic acidosis. Patients suffering from SBS [short bowel syndrome], abnormal gut flora and/or malabsorption syndromes [like people with Crohn’s and autism] are at increased risk for thiamine deficiency. This deficiency, when paired with the elevated lactate production from abnormal gut flora, may lead to large amounts of excess lactate that cannot be effectively metabolized.”[v]
Now I’m going to really be showing my age here but…do any of you autism parents remember TTFD? Probably not unless you’re an autism old-timer like me. For reasons I will never know, TTFD got dropped like a proverbial hotcake…in spite of the fact that in my experience, in a few kids, it literally worked miracles.
TTFD stands for thiamine tetrahydrofurfuryl disulfide, and is just a form of vitamin B1, thiamine. 15 or more years ago, a doctor named Derrick Lonsdale, who at one point was the head of Biochemical Genetics at the Cleveland Clinic, but ended his career focusing on inborn errors of metabolism, noticed that children on the spectrum had signs of thiamine deficiency.[vi] He did a small pilot study on 10 children with autism and found that 8 of them measurably improved when given TTFD.[vii]
Now if I can just personalize this story once more: back in the early 2000’s, I was working as a special education teacher, and had one little boy, just 2 ½, who was profoundly on the spectrum. When I saw him on a Friday, he had no eye contact, very few singleton words, no social behaviors. I was still working on getting him to point to request an item. I walked in 5 days later, on Wednesday, and he looked straight at me, smiled, and pointed out the window, happily announcing, “I see Judy’s car.” In all my years in autism, I’ve never witnessed that kind of miracle, before or since. After I got my jaw up off the floor, I asked his mother what had happened…and what had happened was she’d started TTFD 4 days before. That child came off the autism spectrum in 5 days. (The end of that story, by the way: that child has now graduating from an elite private school and gone off to college.) And by the way, this child was not the only one I’ve seen have a dramatic response to TTFD.
Well, now my curiosity was really peaked, as you can imagine. It turns out that thiamine is kind of a treatment, in those deficient, for d-lactate acidosis! So I really got to wondering, has anyone looked into d-lactate acidosis as a potential factor in autism, especially considering their gut issues and poor carbohydrate digestion/absorption. I did a search and I found a reference to it in an article[viii] written by Elaine Gottschall, the author of Breaking the Vicious Cycle[ix], the book that lays out the Specific Carbohydrate Diet: “Coleman and Blass in 1985 in The Journal of Developmental Disorders reported the first evidence that autism might be linked to carbohydrate metabolism (digestion). These researchers reported that the syndrome of D-lactic acidosis was found to be present in autistic children. Their work was based on reports of the 1970’s and 1980’s showing that undigested carbohydrates were being changed by bacterial action in the intestine to a substance, D-lactic acid. High amounts of D-lactic acid in the bloodstream have been found to cause bizarre behavioral symptoms.”
I bothered my librarian friend at the Columbia University medical library, requesting a copy of that Coleman and Blass article.[x] (Oh, the joys of being an A-type!) To be 100% accurate: they do not specify that they found d-lactate acidosis. They only measured overall serum lactic acid. It’s probably safe to assume then that d-lactate was high but…it is still an assumption. (I’m not even sure if d-lactate could be specifically measured back then.) Still, Dr. Coleman and Dr. Blass were way ahead of their time in their interpretation of their findings: “Lactic acidosis…is not a specific biochemical abnormality. Rather, it indicates some abnormality in the utilization of sugar…The data described above thus suggest that the autistic syndrome can be associated with a family of disorders of carbohydrate metabolism…”
So apparently there is a teeny bit of direct evidence that d-lactate acidosis is an issue in autism. It is very surprising to me that there hasn’t been more exploration of this, considering, as I said above, the signs of symptoms of autism, the known carbohydrate digestion issues, the question of thiamine deficiency raised by Dr. Lonsdale, and so forth.
I wasn’t that surprised that there is also some evidence that chronic fatigue syndrome has some overlap with D-lactate acidosis. I found that as early as 2009, researchers were pointing out, in a very meaningful sample size, major differences in the amounts of lactic-acid producing bacteria in those with CFS (108 patients) versus controls (177 people). “Patients with chronic fatigue syndrome (CFS) are affected by symptoms of cognitive dysfunction and neurological impairment, the cause of which has yet to be elucidated. However, these symptoms are strikingly similar to those of patients presented with D-lactic acidosis….This study suggests a probable link between intestinal colonization of Gram positive facultative anaerobic D-lactic acid bacteria and symptom expressions in a subgroup of patients with CFS.”[xi] Another study, published in 2017, looked at case reports published between 1965 and 2016, and found “The majority of neurological disturbances reported in d-la episodes overlapped with ME/CFS symptoms. Of these, the most frequently reported d-la symptoms were motor disturbances that appear more prominent during severe presentations of ME/CFS. Both patient groups shared a history of gastrointestinal abnormalities and evidence of bacterial dysbiosis…”[xii]
To sum up: recently published papers state that d-lactate acidosis is a poorly recognized condition in many instances, as the symptoms overlap other illnesses. Doctors have been trained to look for it only in the standard at-risk person: those who have had bowel re-section surgeries. And as ordinary labs can’t test for it, it makes the likelihood of diagnosis even smaller. (Ordinary labs though can test of lactic acidosis.) The treatment consists of dietary changes (i.e. lower carbohydrate diets, adequate hydration, in some cases, antibiotics, and cautious use of d-lactate free probiotics.[xiii] (I’ll write more about this in a future post…coming soon.)
We can only hope that the future sees more research into this as the incidence of IBD, autism and chronic fatigue are all on the rise – perhaps d-lactate acidosis is as well. In the meantime, treatment is not complex and can have huge health implications.
[i] Kowlgi, NG, Chhabra, L. D-lactic acidosis: an under recognized complication of short bowel syndrome. Gastroenterology Research and Practice. 2015:476215. doi: 10.1155/2015/476215
[ii] White, Luke. D-lactic acidosis: More prevalent than we think? Nutrition Issues in Gastroenterology, Series #145. Practical Gastroenterology. 2015.
[iii] Williams, BL, Hornig, M, Buie, T, Bauman, HL, Paik, MC, Wick, I, Bennett, A, Jabado, O, Hirschberg, DL, Lipkin, WI. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One. 2011. 6;9:e23585.
[iv] White op. cit.
[vii] Lonsdale, D, Shamberger, RJ, Audhya, T. Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study. Neuro Endocrinology Letters. 202:23(4):303-8.
[ix] Gottschall, E. Breaking the Vicious Cycle. Ontario: The Kirkton Press. 2000.
[x] Coleman, M, Blass, JP. Autism and Lactic Acidosis. Journal of Autism and Developmental Disorders. 1985 Mar;15(1):1-8.
[xi] Sheedy, JR, et. al. Increased d-lactic acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo. 2009: vol. 23 no. 4 621-628
[xii] Wallis, A, Ball, M, McKechnie, S, Butt, H, Lewis, DP, Bruck, D. Examining clinical similarties between myalgic encephalomyelitis/chronic fatigue syndrome and d-lactic acidosis: a systematic review. Journal of Translational Medicine. 2017;15:129.
[xiii] White op. cit.