Here is a sample entry from our student Q&A Treasure Chest which features hundreds of similar topics, available as an ongoing resource for our Semester students. Remember our student body is highly diverse! So both foundational and more complex concepts are presented.
I’m hoping you can help me with this patient before he comes in next week. He is a 17 y/o who has been dealing with Hidradenitis Suppurativa (HS) since the start of puberty. He has multiple enzyme abnormalities including:
Pyruvate dehydrogenase deficiency – builds up pyruvic acid and ketoacids
MSUD (also a dehydrogenase) building up BCAA levels and organic acids.
Arginine, histidine, and taurine are deficient in the plasma.
I’m comfortable giving him the supplements for methylation, but I’m not sure how to proceed with his diet.
I think he should be on low sugar, so he doesn’t build up pyruvic acid or lactic acid. However, if he eats fat, he reports more skin lesions. What about vitamin A to dry up the lesions? Maybe Carrot juice? What am I missing? I need to give my health coach some guidance.
These are specific organic acids, that is metabolic byproducts which are measurable in urine and which can reflect specific nutrient deficiencies or suboptimal biochemical reactions in the body. Indeed, this is an advanced type of testing that takes quite a bit of practice to master; we offer a Deep Dive clinical course on this topic for advanced students: Organic Acids Testing clinical course.
A few national labs offer this testing which (in my opinion) is one of the most valuable and broadly exploratory testing panels one can do under the functional medicine umbrella. You might enjoy looking at sample test results and interpretive guides for some of them to begin to build your knowledge now (e.g. Genova’s Organix (here and here) and Great Plains’ Laboratory’s Organic Acids Test). Contrary to a common misunderstanding, a panel of organic acids is also available from common regional labs in the US (e.g. Quest, Labcorp), but the data may be more cumbersome to review or interpret as presented (and detail may not be shown at all if results are within normal ranges, preventing more esoteric assessment of suboptimal levels).
First of all, let’s review a bit about Hidradenitis suppurativa (sometimes called acne inversa). This is typically a chronic inflammation of the sweat glands which become clogged with keratin. There is disagreement in the medical literature as to whether there is potentially an autoimmune component to this condition, e.g. there is a demonstrated coincidence with Crohns disease. Research into bacterial infections as a contributing cause has shown mixed results, as different species and infections at different levels within the tissue occur (though strains of Staph appear to be most common). What we know for sure is that imbalances in androgen hormones definitely play a role (just as they often do with typical acne or acne vulgaris). Generally in young men with typical modern lifestyle habits, there is an issue with regard to over-conversion of testosterone to dihydrotestosterone (DHT, a stronger androgen), and there is evidence of effective pharmaceutical invention addressing this very dynamic. there may be issues with over-exposure to xenoestrogens as well. People who don’t methylate well may also have more trouble with hormone balance due to impaired detoxification/excretion. We know there is a strong association between HS and insulin resistance. There is also a strong association between higher insulin levels (from insulin resistance) and higher level of 5-alpha reductase (5AR) (that would promote metabolism of testosterone into DHT). The combination of vitamin D, Vitamin A, and zinc is obviously key for immune strength, and there’s interesting research on the possible role of infectious agents and biofilm in chronic HS (whether this is cause or effect – or both – is of course unclear). I recommend checking fasting insulin, HbA1c, RBC Zinc, Vitamin A, Vitamin D, and ideally, an EFA panel.
As you know, zinc is absolutely critical for controlling 5AR activity and preventing over-conversion to DHT. If no data is available, I would recommend supplementing with zinc picolinate (30-40mg/day) for a one-month trial. Various herbs can also be helpful toward this goal (e.g. saw palmetto). There is a blend by Gaia Herbs called Prostate Health that I often recommend for this purpose. Because there is evidence that those with insulin resistance may not well convert beta carotene to Vitamin A, I would focus on sources of whole Vitamin A that this young man can consume regularly. Liver (pate?) might be a stretch, but whole eggs are a good idea; to your comment, short-term boost supplement use may also be prudent if labs are suboptimal (and may affirm poor fat metabolism/absorption in the gut).
You don’t describe this young man’s baseline diet, though certainly that of most 17 y/o patients in the US would be quite poor and loaded with refined, processed foods, both high in artificial ingredients (and perhaps caffeine) and low in nutrients. Obviously you’ll want to work with him on low-hanging-fruit better choices like getting rid of soda and other sweetened beverages and simply choosing to eat a rich of mix of real, whole foods vs. (what Michael Pollan calls) “edible food-like substances”. Otherwise, what I would recommend for general diet is likely obvious to you and includes a low-glycemic diet with these details:
Of course, how much of this your patient is willing or able to do is up to him! I hope this is helpful for sharing with your on-staff health coach.
But let’s look at some aggregate observations from all this data…
I do definitely agree with broad-based B vitamin support in light of all these lab data, especially given the truly dramatic elevations you report. FIGlu that high is especially notable for bioavailable folate deficiency, and this may be why his histidine is low (and also is there perhaps high demand for histamine?). It’s also true that lack of adequate B12 and B6 can drive FIGlu up; he may also struggle with methylation polymorphisms (e.g. MTHFR). Since methylation is a lynch pin for detoxification and folate is key for neurotransmitter balance, I would be cautious to add it very slowly and ramp over time depending on his reaction to it. I would start with 400mcg and stay there for at least the first ~3 weeks.
I believe that elevations in all three of the alpha-keto acids you list AND pyruvate are a clear indication of impairment in the dehydrogenase complex and a potent need for more thiamine (Vitamin B1). Given the acute elevation, actually, it’s quite possible that he has a genetic polymorphism that drives this need. These coenzymes also require other B vitamins (e.g. B2, B5) and alpha lipoic acid, but B1 is the dominant co-factor. Reversing any insulin resistance (elevated fasting insulin e.g. upper half of fasting insulin RR) to prevent high circulating insulin from further complicating his hormone balance is key to optimizing his cellular energy production.
b-Hydroxyisovaleric acid is a sensitive marker for biotin deficiency, Vitamin B7, which is critical for skin health. This deficiency could also be at play in exacerbating his insulin resistance.
Methylmalonic acid is a very sensitive marker for Vitamin B12 deficiency. Again, the extreme elevation in these markers quite conclusively indicates a need for more nutrition and (assuming he’s not living on junk food) likely indicates issues in the gut with nutrient malabsorption which really need to be explored more fully. Is there gross malabsorption of nutrients? Or grossly poor intake of nutrients? Are you concerned about dysbiosis/SIBO/pathogens in the gut possibly at play in driving malabsorption? Another interconnectedness here might be the likelihood of insufficient stomach acid (due to low histidine) and that this could easily promote poor amino acid absorption as well as lower levels of B vitamins (especially B12).
The possible combination of insulin resistance and possible fat malabsorption (or poor mitochondrial handling of fatty acid oxidation) is notable! As is the need for B vitamins. Taurine is made in the body downstream from methylation with Vitamin B6 (P5P) as a key cofactors. Poor fat/bile reabsorption may be contributing to lower plasma taurine levels (as well as poor response to higher intake of dietary fats – and of course make sure that “eating higher fat” to him does not correlate with highly refined, inflammatory vegetable oils; inflammation can increase synthesis of DHT).
In light of all these data, in terms of helpful supplements, I recommend considering (adding only one at a time, of course): zinc (as above), a DHT countering formula (as above), a moderate B-complex e.g. Thorne’s basic B-complex (perhaps only half cap for first week?) , an EPA/DHA and GLA combination (e.g. Metagenics EFA Combination), and a combination digestive formula (e.g. Designs for Health’s DigestZymes). Again, given the magnitude of these OAT findings, I believe it’s key not to push too hard too quickly as potentially long-dormant pathways get fired up again across many body systems.
Again, I would think carefully too about other exacerbating factors as puzzle pieces in this case e.g. gut microbial imbalance and sources of stress that might further hormone imbalance (e.g. insomnia).