Exposing Harmful Supplements: Biotin's Dark Side
This is how to use a simple home measurement to expose the harmful effects of a supplement before they even happen.
In January of this year, having finished my Self-Experiments in the Biochemically Unoptimized State, based on the rationale outlined in Getting to the Bottom of My Health: Biotin and (V)LCAD, I started phase I of my biochemical optimization experiments with a 10 milligram loading dose of biotin.
Five weeks into this, I developed clumsiness, short-term memory loss, and a quick temper.
Several times a day, I would experience an unusual degree of clumsiness, such as my phone flying out of my hand when I was simply holding it. Several times I would walk into a room and be unable to remember why I went there. In one event, I screamed at someone for something trivial, and screamed so loud I saw flashing yellow lights spinning around me, which I assume was from a sudden massive rise in blood pressure.
I also wrote in my notes that I seemed to be developing the beginnings of a gait abnormality, but it was hard to distinguish from whether my hips were too tight.
Yet that also betrays another problem: my muscle tension was increasing.
What happened?
An early clue was that my waking resting lactate was increasing.
My average waking lactate had been 0.6 mmol/L, but biotin brought it up to 1.1 mmol/L, and led to numerous days where it was considerably higher, including 2.0 mmol/L on the last day of the high dose.
When I stopped the biotin, the problems went away and my lactate returned to normal.
This can be explained rather easily from a biochemical perspective:
Energy metabolism can be broadly conceived as a two step process. Step 1 is the catabolic breakdown of carbs, fat, and protein to extract energy in the form of electrons. Step 2 is the translation of that energy into ATP using oxygen.
Biotin contributes to step 1 in multiple ways, but does nothing to step 2.
If step 2 is compromised more than step 1, biotin, thiamin, or any other nutrient that contributes to step 1 without contributing to step 2 will be detrimental to one’s energy metabolism.
Lactate rises when step 1 exceeds step 2, so waking fasting lactate is an excellent leading indicator of the health problems that could result from aggravating an imbalance between step 1 and step 2.
Consistent with this, I recently tried thiamin, which falls into the same category. 125 milligrams brought my waking lactate the next day to 1.7 mmol/L. I cut it down to 25 milligrams, and this brought my waking lactate the next day to 2.5 mmol/L. I ditched the thiamin. My lactate went back to normal. No problems resulted because I used lactate as a leading indicator and averted the neurological problems the thiamin would have presumably caused me had I kept it up.
Am I the only person this happens to? I seriously doubt it.
In a Q&A session from May of this year, I mentioned this, and one member whose primary issue is respiratory chain impairment said they believe the same thing happened to them on eight milligrams of biotin per day.
In my case, my one set of mutations to rule them all is two rare mutations in ACAD9, a riboflavin-dependent gene needed for fatty acid oxidation (a component of step 1) and for the proper assembly of complex I of the mitochondrial respiratory chain (a component of step 2).
Biotin overactivated different parts of step 1 (oxidation of certain amino acids, fatty acids, and use of carbohydrate to fuel the citric acid cycle) but did nothing to help step 2, so caused lactate to go up and neurological problems to ensue.
Thiamin likely did the same thing by promoting the use of carbohydrate to fuel the citric acid cycle and doing nothing to help step 2.
I now strongly believe that measuring glucose, ketones, and lactate simultaneously should be the centerpiece of dealing with any metabolic issue and should absolutely be done when trialing supraphysiological doses of any vitamins or minerals.
Lactate, in particular, seems to be the most useful indicator of an imbalance. Resting lactate should be 0.5-1.5 mmol/L, with 0.5-0.9 being the healthy range for fasting, and meals should increase it within the normal range, especially when they contain carbohydrate. Increases of waking lactate above 1.0 or postprandial lactate above 1.5, or any major increases of lactate even within the normal range in response to supplementation, should be seen as leading indicators of metabolic impairments caused by supplementation.
I use a NovaBiomedical Lactate plus.
Prime candidates for supplements that could raise lactate in this manner are thiamin, B6, and biotin, and perhaps manganese, though this is not at all a complete list. The fact that nearly everyone has several highly idiosyncratic bottlenecks in energy metabolism means that some supplements such as riboflavin that could be generally supportive of step 2 in most people will disproportionately or even exclusively support step 1 in others.
There are 297 independent genetic impairments in step 2, many essential nutrients that are relevant, and many toxins that impair it. There are no general rules for what helps it, there are, rather, a great many things that can help some and hurt others. These will be the subjects of future articles. For now, the point is that if you are supplementing with something that is overburdening such an impairment, you do not need to know what the impairment is to apply common sense, see the rising lactate, and either cut back or cut out the supplement before some type of harm sets in.
As I described in Why You Need THIS Supplement on a High-Protein Diet and Why High-Dose Biotin Could Be the Answer for Your Blood Sugar, Neurological Health, and Skin Health, most people need more biotin than they get, and about one in thirty people likely need milligram doses per day.
So, this is not a warning that biotin is bad for you, even at high doses.
Rather, if you want to know whether a supplement is doing good or doing harm, one excellent tool. in your kit is to test your waking, fasting lactate.
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How is Step 2 best supported?
I'm sure this is relevant to lots of people with CFS and fibro regardless of taking biotin.
thanks Chris - always interesting and helpful!
You can find tons of people on thiamine facebook groups experiencing this, I think. They often call it "paradoxical effects", and some actually seem to snap out of it after a while, but quite a few don't. Personally, I experience similar issues with benfotiamine and biotin. Biotin is quite immediate, while benfo took a little longer to mess me up.
I'm very interested in what exactly is the biochemical process that generates the symptoms. I would assume that it's not just lactate itself, but also the superoxide or hydrogen peroxide produced in ETC in those who have issues with it or is it something else?