Mescreen or MitoSwab for mitohealth? Other mitochondrial tests?

[AlexKChen]

How it works

MitoSwab. Very happy with their reports. Not only looks at your level of mitochondrial activity but also channel efficiency.

Chad Lerner is fun to talk to

[RapAdmin]

Interesting… launched this past summer, and sounds like its more for research than personal use:

Verséa Discovery, Inc. Announces the Official Launch of mescreen™ Research Validator – a Revolutionary Mitochondrial Compound Assessment Platform

August 27, 2024 06:00 AM Eastern Daylight Time

TAMPA, Fla.–BUSINESS WIRE–Verséa Discovery, Inc., a Florida-based company dedicated to advancing scientific research and development in the area of personalized and precision medicine, has announced the official launch of mescreen™ Research Validator.

The mescreen™ Research Validator is a groundbreaking, proprietary compound assessment platform that harnesses mitochondrial function and dynamics to generate critical data, supporting the development, formulation, and clinical validation of customers’ supplements, nutraceuticals, pharmaceuticals, biologics, and medical devices.

By utilizing patented optimized bioassay, imaging, and machine-learning process, the mescreen™ Research Validator delivers valuable insights into mitochondrial efficiency and the clinical effects of various test materials in-vitro and in-vivo.

Research utilizing Verséa’s proprietary machine learning system has analyzed over 60 FDA-approved compounds and probes known to impact mitochondrial function and dynamics. These studies have demonstrated the platform’s capability to detect changes in mitochondrial function and structure upon the introduction of test materials into the assay. The platform is also able to detect changes in mitochondrial function when therapeutics, interventions and lifestyle changes were introduced to and implemented by subjects.

“We are thrilled to bring this groundbreaking technology to market,” said Stephen Porada, the President of Verséa Discovery, Inc. “mescreen™ Research Validator has tremendous potential to help companies validate or optimize the performance of their bioactive molecules, ingredients or physical interventions being targeted for commercial product development.”

Dr. Hemal Patel, Chief Scientific Advisor of Verséa Discovery, Inc., added, “In addition to this important advancement, we are currently developing the mescreen™ Personalized Mitochondrial Efficiency Test, which aims to provide individuals with a comprehensive energetic profile. This test will utilize a 12-matrix panel to accurately quantify core functions and dynamics providing important data and information related to one’s mitochondrial efficiency. Our commitment to enhancing mitochondrial health will empower individuals to better understand and improve their well-being.”

To gain insight into the science behind mescreen™ Research Validator and explore how it can benefit your research and product development efforts, please contact Verséa Discovery, Inc. at discovery@versea.com or call 1-800-397-0670.

About Verséa Discovery, Inc.

Verséa Discovery, Inc., headquartered in Tampa, FL, is a U.S. company committed to advancing scientific research and development in personalized and precision medicine. Operating as a strategic business unit of Verséa Health, Inc., the company specializes in developing innovative solutions that deliver critical insights into health at the cellular and mitochondrial levels. To learn more visit Verséa Discovery webpage.

Disclaimer: mescreen™ is for research use only and is not intended to diagnose, treat, or cure disease. You should not change medications, diet, exercise regimens, or other related health activities without consulting your physician. mescreen™ has not been reviewed by the Food and Drug Administration. mescreen™ is a trademark of Verséa Health, Inc.

[adssx]

I checked this company months ago as they have (had?) a lactoferrin test that could be used for the early diagnosis of Parkinson’s and/or Alzheimer’s. That test was very serious. I don’t know about this new mitochondria test though.

[AlexKChen]

https://x.com/trikomes/status/1924906797200245138

The dashboard you’re looking at is not an organic-acids profile.
It comes from a direct enzyme-activity panel that the lab runs on the mitochondria-containing cells in your blood sample (mostly platelets and leukocytes). In each well of a micro-plate the lab:

1. immuno-captures one respiratory-chain complex (or citrate-synthase as a reference),
2. adds a very specific substrate/cofactor mix, and
3. follows the initial reaction rate by watching a change in light absorbance.

What is being quantified in each well is therefore an enzyme-catalysed reaction rate, not a circulating metabolite.
Here are the actual reactions and the “reporter” signals the spectro­photometer tracks:

Report line	Enzyme reaction in the assay well	Spectral “reporter” that is monitored
Complex I (NADH dehydrogenase)	NADH → NAD⁺ + H⁺ (electrons passed to ubiquinone analogue)	Disappearance of NADH at 340 nm
Complex II (Succinate dehydrogenase)	Succinate → fumarate (electrons to CoQ analogue)	Reduction of DCPIP or decyl-ubiquinone (600 nm)
Complex II + III (Succinate : cyt-c reductase)	Succinate → fumarate → cytochrome c (via complexes II & III)	Appearance of reduced cytochrome c at 550 nm
Complex IV (Cytochrome-c oxidase)	4 Red-cyt-c + O₂ → 4 Ox-cyt-c + 2 H₂O	Loss of reduced cytochrome c absorbance at 550 nm
Citrate-synthase (normalises for mito number)	Oxaloacetate + Acetyl-CoA → Citrate + CoA-SH	Formation of TNB from CoA-SH + DTNB at 412 nm

So the only “analytes” the instrument is reading are:

• NADH (Complex I)
• DCPIP / ubiquinone analogue (Complex II)
• Reduced cytochrome c (Complex II + III and IV)
• TNB (Ellman’s reagent product) for citrate-synthase

The green/orange gauges you see are simply each reaction rate normalised to citrate-synthase activity and then expressed as a percentage of a healthy-control mean. No plasma metabolites (lactate, succinate, organic acids, etc.) enter into these particular numbers.

[cl-user]

Is that another mitochondrial test?

[AlexKChen]

3.5 Keys to Improving Mitochondrial Health

Mhi

[snowfall]

Thank you for this. I had a full genome test suggesting that I have some degree of Complex I deficiency as well as an OAT test showing something similar. Would be cool to see it confirmed again here because I am not a genetics expert and didn’t know what I was doing with the whole genome data.

I won’t be trying this though because I think the price is unreasonable. The cost of the full genome test and the OAT test combined was still much less than this. I’ll keep my eye out for similar tests.

This is a test I heard of a while back: https://www.iollo.com/

Pricy, but still less than the Mescreen. Can’t vouch for it other than I heard of it years ago and bookmarked it.

[AlexKChen]

Introducing Mitome

It’s just a cheek swab, I really don’t know if it can be this informative…

[Bicep]

Only $700 though. I like Chris and even subscribed for a couple years, but don’t know about this.

[AlexKChen]

The Mitome test had showed that this client had impaired transport of methyl groups into the mitochondria, and since creatine supports methylation, this may have made him respond especially well to the creatine. However, everyone needs to optimize their creatine status so this is a safe and fruitful path to embark on without testing first.

Mitome reflects a year and a half of deep research into the causes of many different patterns of mitochondrial dysfunction, fused with my own cross-referencing over 100 sets of respiratory chain data with comprehensive whole genome sequencing and biochemical data (amino acids, organic acids, vitamins, minerals, and other markers) to distill ways of inferring causal patterns and effective actionable protocols from repeatable patterns within the respiratory chain data when used on its own. Mitome uses a cheek swab to measure each of the four respiratory chain complexes where 90% of your cellular energy (ATP) is made to infer which of 12 “mitochondrial types” you are and how your patterns combine into one of 90 unique approaches to personalizing your strategies to boost your cellular energy production. Mitome also simplifies this for you by automatically constructing your protocol for you. Find out your mitochondrial type today with Mitome.

[AlexKChen]

Short answer: partly.

What’s solid: Mitome’s cheek-swab labwork appears to be run on/with the MitoSwab platform. Buccal (cheek) cells can be used to measure mitochondrial enzyme activities (e.g., Complex I, III, IV) and citrate synthase, and there’s peer-review showing these buccal assays track muscle-biopsy enzyme defects ~82% of the time for Complex I/IV in confirmed mitochondrial disease (small, pediatric cohort).

What’s iffy: Mitome markets a personalized “optimization protocol” from those cheek-cell readings. That interpretive algorithm and clinical benefit (e.g., better symptoms/outcomes because you followed their supplement/diet plan) haven’t been validated in published trials, and the underlying test is a CLIA LDT, not FDA-cleared. Price listed is $699.

The “only cheek cells” concern (you’re right)

Mitochondria vary a lot by tissue (proteins, assembly, morphology, fuel use). Cheek epithelium is not a stand-in for brain, heart, liver, or skeletal muscle. Also, buccal epithelium turns over fast (~14 days), so a swab reflects recent state and local exposures (diet, smoke/vape, oral inflammation), not “whole-body mitochondrial health.”

What Mitome says it measures

Their page lists citrate synthase plus Complex I, II, II+III, and IV from a cheek swab; they then generate food/supplement suggestions. (Note: “II+III” is an activity assay, not a single complex.)

How good are cheek-swab enzyme assays?

Pros: Non-invasive; methods exist for CI/CIII/CIV. One 2012 study reported ~82.5% correlation with muscle biopsy for CI/IV in diagnosed cases; a 2023 paper details buccal Complex III assays.

Caveats: Small cohorts; CI/IV most studied; diet/smoking can modulate buccal mitochondrial readouts; and results may not mirror high-energy tissues. The test is not diagnostic on its own.

If you want a more “systemic” readout

Some groups measure mitochondrial respiration in blood cells (PBMCs/platelets) and show links to muscle and clinical states, but these, too, have confounders (immune-cell mix, methods) and are mostly research-setting.

Practical take

Consider Mitome as a screening/monitoring tool, not a verdict on body-wide mitochondria.

If you do it, standardize pre-collection: follow their instructions (rinse with water; wait 30 min after brushing; ship Mon–Thu on ice) and avoid acute confounders (smoking/vaping right before sampling).

For organ-specific symptoms (e.g., neuromuscular issues), see a specialist; gold-standard workups still rely on targeted clinical testing.

Bottom line: The measurement part (cheek-cell enzyme activities) has some peer-reviewed support; the “personalized protocol” part is not clinically validated. Treat Mitome as potentially informative but non-diagnostic, and be cautious about over-interpreting cheek-cell data as your global mitochondrial status.

[AlexKChen]

I got my results back. They were very simple. I guess I need to supplement with CoQ and also it may be better for me to stay away from statins.
(and MAYBE i might benefit from methylene blue)

Complex I
Normal
136%

Complex II
Normal
107%

Complex II + III
Low
23%

Complex IV
Normal
80%

Citrate Synthase
High-Normal
171%

Results Summary
Your mitochondrial complex II + III activity is at 23% of normal function. These
enzyme complexes are critical components in the electron transport chain—the
cellular pathway that produces most of your ATP (energy). This blockage impairs
your cells’ ability to metabolize all fuel types. The dysfunction substantially
reduces your energy production, affecting both your daily performance and your
body’s capacity to maintain long-term health functions.
Overall, this means you may benefit from CoQ10, vitamin C, vitamin K2 (in the
form of MK-4), sulfur amino acids, near infrared light in the 700-1000 nanometer
range, methylene blue, and the removal of complex III inhibitors from your diet,
lifestyle practices, and medications.

===

The table below gives normal ranges based on 95% confidence intervals in control samples. Your
percentages listed on the previous page are a percentage of the mean control. For example, if your
citrate synthase was “100%,” you can derive its activity in nanomoles per minute per milligram buccal
protein by multiplying 100% times 12.1 in the below table, meaning it was operating at 12.1 nanomoles
per minute per milligram buccal protein. You can then compare that to the normal range and conclude
that it is normal.
Due to the lack of large sample sizes and associated statistical precision in these normal ranges, the
Mitome analysis categorizes results as a percentage of control means into normal (70-140%), low (≤
50%), high (≥ 200%), or low or high normal between these ranges, based on standardized cutoffs for
the sake of optimal pattern analysis. This is the basis for the descriptors you see on the previous page
and for any patterns we derive from those descriptors.
Enzyme Normal Ranges and Mean Activities
Activity Name Normal Range Mean ± SD
Citrate Synthase (CS) 4.4-22 12.1 ±5.1
Complex I
(normalized to CS)

3.4- 11.9
6.8 ±2.0

Complex II
(normalized to CS)

0.03-0.35
0.194 ±0.08

Complex II + III
(normalized to CS)

0.032-0.152 0.092 ±0.03

Complex IV
(normalized to CS)

0.15- 0.6 0.31 ±0.1

[AlexKChen]

Got it. I converted your Mitome percentages to the underlying values using the report’s own rule:

raw value = (your %) × (control mean) / 100.

I’m keeping the original units exactly as the table states. For the complexes, the “raw” unit is the activity normalized to citrate synthase (a unitless ratio, by assay convention). Citrate synthase (CS) is in nmol/min/mg buccal protein.

Raw values (from your percentages)

Assay	Your % of control mean	Control mean	Raw value	Reference range
Citrate Synthase (CS)	171%	12.1 nmol/min/mg	20.7 nmol/min/mg	4.4–22 nmol/min/mg
Complex I (normalized to CS)	136%	6.8	9.25	3.4–11.9
Complex II (normalized to CS)	107%	0.194	0.208	0.03–0.35
Complex II + III (normalized to CS)	23%	0.092	0.0212	0.032–0.152
Complex IV (normalized to CS)	80%	0.31	0.248	0.15–0.60

Notes: values rounded to 3 significant figures. “Normalized to CS” is a dimensionless ratio per the lab’s method.

Optional: absolute activities for the complexes (nmol/min/mg), assuming “normalized to CS” = complex rate / CS rate

If we take your CS rate as 20.7 nmol/min/mg and multiply by each normalized ratio, we get approximate absolute rates for the complexes:

• Complex I ≈ 191.35 nmol/min/mg
• Complex II ≈ 4.295 nmol/min/mg
• Complex II + III ≈ 0.4378 nmol/min/mg
• Complex IV ≈ 5.131 nmol/min/mg

Caveat: labs typically interpret complexes via the CS-normalized ratios, not these derived absolutes. I’m showing them because the math is straightforward and sometimes useful for cross-assay comparisons, but clinical interpretation usually sticks to the normalized numbers.

If you want this as a CSV for your notes, say so and I’ll spit it out.

===

Short answer: a choke point at complex II+III can hit both ATP and ROS. It’s not just “low energy.” When electrons pile up before complex III, they leak. Leaky electrons make superoxide, especially at complex III’s Qo site. Chronic over-reduction there is linked to redox stress, hypoxia signaling, and downstream damage. So yes, this pattern can contribute to aging biology via ROS signaling, not only fatigue.

Here’s how I’d think about fixes, in order of “likely to help / low regret”:

1) Treat this like a Q-junction bottleneck

Your isolated drop in “complex II+III” with normal II, I, and IV is the classic footprint of a coenzyme Q (CoQ) bottleneck: the assay literally depends on II handing electrons to CoQ which then feeds III. If the Q-pool is thin or sluggish, II+III reads low even when II and III themselves test fine. That exact pattern is widely reported in CoQ deficiency workups, which is why labs use the I+III and II+III “segments” as CoQ-dependent screens.

Practical next steps:

• Measure CoQ10 status with a clinically useful matrix. Plasma is common but tracks lipoproteins; leukocytes/fibroblasts or muscle are better if you’re going for precision. If it’s low or borderline, you have a clean target.
• Scan meds/exposures that punish the Q-junction or complex III:• Statins consistently lower circulating CoQ10. Not a hard stop, but it’s a confounder and a reason to supplement if you must stay on them.• Atovaquone is a bona fide complex III inhibitor.If either applies, that’s low-hanging fruit.

2) Core interventions

CoQ10 (prefer ubiquinol): despite mixed RCTs, mitochondrial guidelines still recommend offering CoQ10 given mechanism, safety, and case-level benefits. Typical adult doses used clinically are 200–600 mg/day with fat, often split. Recheck symptoms and, if you want to be data-driven, re-measure a CoQ marker or repeat the buccal assay after 8–12 weeks.

Riboflavin (B2): supports FAD-dependent complex II flux feeding the Q-pool. Common mitochondrial doses are 100–200 mg/day. Evidence base is small/open-label, but the risk is low.

Photobiomodulation (near-IR ~670–850 nm): repeatedly shown to upregulate cytochrome c oxidase activity and improve mitochondrial performance, with aging-offset effects in animal and human studies. If you use it, think small spot size, a few minutes per site, several times per week.

Antioxidant/GSH support: Vitamin C, alpha-lipoic acid, and sulfur amino acids/N-acetylcysteine help control the ROS spillover while you fix throughput. This is standard supportive care in mitochondrial medicine, even if hard outcome trials are scarce.

Training, not overtraining: Zone-2 aerobic plus resistance training expands mitochondrial content and capacity, which raises headroom at the same load. Start modestly if you’re symptomatic and progress weekly. This is boring, but it compounds. (General principle from mitochondrial rehab literature.)

3) Where methylene blue and metformin fit

Methylene blue (MB): cautiously promising, with caveats.

Low-dose MB can accept electrons upstream and donate directly to cytochrome c, effectively creating a side-route that lessens traffic through I→Q→III. In models it enhances respiration, raises ATP, and lowers ROS when dosed low. Translation: it can relieve the pressure that makes complex III leak. But it will not “repair” a depleted Q-pool, and evidence is mixed on whether MB truly bypasses a hard complex III block in living cells. If you try it, do it supervised.

Safety you should actually care about: MB is a MAOI at clinically relevant doses. It can precipitate serotonin syndrome with SSRIs/SNRIs/TCAs, and G6PD deficiency is a red flag. Typical brain/mito protocols use low oral doses (e.g., ~10–30 mg/day, sometimes titrated), but you clear this with a clinician who knows your meds and labs.

Metformin: probably not your friend for this goal.

Metformin inhibits complex I. In the general T2D population, lactic acidosis is rare, but in mitochondrial disease circles it’s on the “use cautiously or avoid if possible” list because it can worsen oxidative phosphorylation and lactate handling. If your priority is energy and you already have a downstream choke, adding an upstream brake is… unhelpful. If you need glycemic control, choose alternatives and decide with your doc.

4) Vitamin K2 (MK-4) reality check

Cool Drosophila paper showed MK-4 acting as a mitochondrial electron carrier and rescuing pink1 phenotypes. Follow-up human cell work failed to replicate functional rescue. Bottom line: keep K2 for bones and maybe extrahepatic vitamin K biology, but don’t expect it to replace CoQ in human mitochondria.

5) A simple, sane plan

1. Confirm: get a CoQ10 level in a useful matrix; review meds for statins/atovaquone or other offenders.
2. Correct: start CoQ10 (ubiquinol), add riboflavin; layer in PBM; use antioxidant/GSH support while throughput recovers.
3. Consider MB only if your med list is clean for serotonergic risks and you have clinician oversight.
4. Re-test in ~8–12 weeks to see if II+III normalized toward the 0.032–0.152 reference band. If it moves up, keep going; if it doesn’t, escalate the workup.

You’ve basically got a Q-junction traffic jam. Clear the jam first (CoQ10, riboflavin, PBM, remove inhibitors), then decide if you want clever detours like MB. Metformin is the opposite of that. If you want, I’ll format this into a one-page protocol you can hand your clinician, minus the eye-rolls.

===

Short version: food can nudge your Q-junction, not bulldoze it. Still worth nudging.

What to eat to “unclog” the II→Q→III handoff

Think “support the Q-pool, feed SDH (complex II), and provide the metal/vitamin parts complex III needs.”

1) Support CoQ10 itself (the Q-pool)

• Eggs, pistachios, peanuts, sesame/tahini, soy have small but real CoQ10. You will not eat your way to therapeutic doses, but these help the baseline. Example numbers: ~2 mg/100 g pistachios, ~2.6 mg/100 g peanuts, ~1.7 mg/100 g sesame.
• Protein for the ring: your body builds CoQ10’s benzoquinone head from tyrosine/phenylalanine, and its tail via the mevalonate pathway. So adequate protein (eggs, soy, legumes) supports the ring, and not kneecapping the mevalonate pathway supports the tail.
• Nerd check: low II+III with normal II is a classic CoQ bottleneck signal on segment assays, i.e., electrons can leave succinate but stall at Q before III.

2) Feed complex II (SDH) cofactoring

• Riboflavin/B2 makes FAD for SDH. Ovo-veg sources: eggs, mushrooms, almonds, spinach, fortified cereals.
• Sulfur amino acids (for glutathione redox support): eggs; plus alliums and brassicas for sulfur chemistry. Not glamorous, actually useful.

3) Build complex III’s “hardware”

• Complex III contains heme b and a Rieske iron–sulfur protein. You need iron, vitamin B6 for heme synthesis, and a little copper to keep iron traffic and cytochrome c oxidase happy. Ovo-veg playbook:
  • Iron: lentils, chickpeas, tofu, pumpkin seeds, spinach + vitamin-C produce to boost absorption.
  • B6: potatoes, bananas, pistachios, sunflower seeds.
  • Copper: cashews, sesame/tahini, cocoa powder.These aren’t random “superfoods”; they’re the parts bin for heme and Fe-S biology.

4) Antioxidant backstop while you fix throughput

• Vitamin C helps recycle the Q/antioxidant network; selenium supports GPx. One Brazil nut now and then covers selenium without detonating your calories. Meanwhile, keep ROS down where it starts: complex III’s Qo site loves to spit superoxide when the Q-pool is over-reduced.

So… is high succinate a clue?

Sometimes. If succinate is high (typically on a urine organic acids test), that can reflect SDH impairment or a downstream handoff problem that causes back-pressure. Succinate is also a signaling metabolite that inhibits prolyl-hydroxylases and stabilizes HIF-1α, which is cool in a paper and annoying in a person. But it’s not specific: microbiome output, hypoxia, hard exercise and other bottlenecks can raise it too. In your pattern (II normal, II+III low), a thin Q-pool can still let succinate creep up because SDH can’t pass electrons to Q fast enough under load. Confirm with CoQ10 status rather than guessing from succinate alone.

Tiny, boring plan that actually works

• Daily: eggs or fortified cereal + leafy greens; legumes or tofu; a tablespoon of tahini or a small handful of pistachios or peanuts; vitamin-C produce with iron-rich meals.
• Weekly: one Brazil nut; mushrooms a few times; cocoa powder cameo if you want copper without a calorie avalanche.
• Supplement layer if you’re serious about moving the needle: ubiquinol CoQ10 and riboflavin remain the heavy lifters; food won’t replace them. Re-check your II+III after 8–12 weeks. The reason is biochemical, not vibes.

Side note, because biology has a sense of humor: when electrons pile up before III, ROS rises right there at complex III. Fixing the throughput tends to help both energy and aging-adjacent redox signaling, not just ATP.

If you want me to turn this into a 1-page grocery + lab checklist, I’ll do it without snark. For once.

[AlexKChen]

I have intermittently taken a few statins every 2 weeks, it’s possible those might be affecting the results…

God, the mitome report was worth it in the end. Yes it’s $600, but $600 still is nothing compared to the insight you can get from this. It’s very actionable, way more so than epigenetic age tests (still) are.

[AlexKChen]

Short version: if your “Q” is low, Complex II can’t hand off electrons efficiently, so flux through succinate dehydrogenase stalls and succinate tends to pile up. Raising the CoQ pool usually relieves that bottleneck and should lower succinate, as long as downstream steps (Complex III/IV) aren’t the real choke point and SDH itself isn’t mutated. (PNAS)

Why that happens, in human terms:

• Complex II oxidizes succinate to fumarate and passes the electrons to ubiquinone (CoQ). If the quinone pool is too small or too reduced, SDH forward flux slows and succinate accumulates. In hypoxia or when the Q pool is over-reduced, SDH can even run in reverse, further boosting succinate. (PNAS)
• Directly blocking the Q-binding site of Complex II is known to raise intracellular succinate; low CoQ is a physiological way of creating a similar “acceptor-limited” state. (Nature)
• Excess succinate isn’t just clutter. It inhibits HIF prolyl-hydroxylases, stabilizes HIF-α, and perturbs dioxygenases tied to chromatin, nudging inflammatory and senescence-adjacent programs. (ScienceDirect)

Will more CoQ help? Often, yes:

• In CoQ deficiency, activities at the II→III segment drop and ROS rises; replenishing CoQ generally improves electron transport and redox balance. That should reduce succinate backlog if the primary issue is limited Q availability. (MDPI)
• Caveats: if Complex II itself is compromised (SDHx or assembly-factor defects), or Complex III/IV are impaired so the Q pool stays reduced, extra CoQ won’t fully fix succinate buildup. Context matters. (FEBS Journals)

If you’re trying to ground this in data rather than vibes:

• When clinicians investigate true CoQ problems, they don’t rely on plasma alone; they look at tissue or cell assays (muscle, fibroblasts, or blood cells) and sometimes organic acids for succinate. That’s the route if you want a hard answer about your Q pool and succinate. (PMC)

Net: low CoQ can absolutely create a functional “Q blockade,” which favors succinate accumulation; restoring CoQ tends to relieve it, provided the rest of the chain can accept the flow. If you’re experimenting, be cautious and loop in a clinician; mitochondria reward precision, not guesswork.

[AlexKChen]

Short version: if Complex II is fine but Complex III is very low, Complex III wins the “makes succinate pile up” contest.

Why:

• SDH (Complex II) can only oxidize succinate forward if it can dump electrons onto an oxidized Q pool. When Complex III is impaired, QH₂ can’t be re-oxidized efficiently, the Q pool stays over-reduced, and SDH forward flux stalls. In that state SDH can even run in reverse (reduce fumarate to succinate), which pushes succinate higher.
• This mechanism is exactly why ischemia or downstream ETC blocks cause succinate accumulation: ubiquinol builds up and drives reverse SDH. Complex III inhibition mimics that downstream choke.

CoQ vs Complex III:

• Low CoQ can also raise succinate by making electron handoff acceptor-limited at the II→Q step, but if Complex III is intact, adding CoQ often restores II+III segment activity and relieves the bottleneck.
• If Complex III is the bottleneck, simply adding more CoQ won’t fix the over-reduced Q pool. You’ve just created more parking spaces for electrons with no exit ramp. Succinate stays sticky.

Practical read:

• With normal Complex II and low Complex III, expect more succinate accumulation than from a comparable CoQ shortfall, and expect limited benefit from CoQ alone unless III function improves. Clinically, this pattern is supported by models where downstream ETC inhibition drives QH₂ buildup and reverse SDH.

I know, mitochondria are drama queens. But your intuition is right: the choke downstream (III) usually pushes succinate harder than a modest lack of courier (CoQ) upstream.