Metabolic Vulnerability Index

#1

Just learned about MVX, the Metabolic Vulnerability Index, which is used to estimate ACM within a 1-5 year period. Attia had the inventor of this biomarker on his latest podcast.

AI summary:

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#2

What separates this risk marker from other risk markers? Itā€™s mainly 2 things:

  • what it measures is not organ-specific, which is why the studies listed above are not limited to a single organ (liver, eyes, thyroid)
  • it doesnā€™t depend on age. As a simplified example, itā€™s able to assign a higher score to someone with a 30-year old patient with untreated FH, vs someone in their 60s with LDL under 55.
  • It is stable, unlike hsCRP and IL-6 levels, which makes it useful for tracking levels for people with chronic diseases.

Fuller explanation from AI:

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#3

Because this looks in part at citrate i looked at the figures in the paper which talked about figures in plasma about 2 micromolar. Normal is more like 100. Odd.

#4

This is from Associations of Multimarkers of Metabolic Malnutrition and Inflammation With Allā€Cause Mortality and Their Interplay With Thyroid Function - PMC

The population is people with low thyroid function, and hence low metabolic rate, so I would expect citrate to be low due to low krebs cycle activity.

#5

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I found one particularly clear extreme in the human literature: postoperative plasma citrate around 60 Āµmol/L. That appears to be among the lowest well-documented values I can find in studies reporting absolute concentrations.

In the classic surgical-stress work summarized by Costello and colleagues, 65 surgical patients were studied. The mean plasma citrate fell from about 112 Āµmol/L preoperatively to 91 Āµmol/L at 1 day, then to 76 Āµmol/L at 2ā€“4 days and 78 Āµmol/L at 5ā€“7 days. In a particularly striking patient with severe hyperparathyroidism, plasma citrate started around 300 Āµmol/L but fell after surgery to approximately 60 Āµmol/L, remaining severely depressed for more than 10 days.

The authors attribute the postoperative fall primarily to a major increase in hepatic clearance and uptake of circulating citrate, rather than increased renal clearance. Their experimental work estimated roughly 55% hepatic extraction of delivered plasma citrate after surgery.

For context, an enzymatic reference study found healthy subjects spanning 80ā€“170 Āµmol/L, with a mean around 120 Āµmol/L. Thus, 60 Āµmol/L is roughly half the usual mean concentration.

Interestingly, several diseases I searched do not produce especially low serum citrate:

Condition Reported citrate behaviour

Major surgery ā†“ strongly; individual values ~60 Āµmol/L
Healthy subjects ~80ā€“170 Āµmol/L
Profound hypothyroidism ā†‘ to 157 Ā± 48 Āµmol/L
After thyroid-hormone replacement ~93 Ā± 25 Āµmol/L
Severe diabetic ketoacidosis Generally ā†‘, sometimes markedly
NAFLD/NASH fibrosis Tends to ā†‘
Hyperparathyroidism Can be markedly ā†‘

The thyroid result is particularly relevant to your earlier question. A recent human study of 16 patients made profoundly hypothyroid after thyroidectomy found citrate of 157 Ā± 48 Āµmol/L. After 20 weeks of thyroid hormone, it fell to 93 Ā± 25 Āµmol/Lā€”a 72% difference. This also confirms the much older observation that myxoedema can be associated with raised plasma citrate.

So far, I have not found a convincing published human plasma/serum citrate measurement substantially below about 50ā€“60 Āµmol/L. Values in the 20ā€“40 Āµmol/L range may exist, but I would not regard them as established from the literature Iā€™ve located.

There is also an interesting implication for the citrate/acetyl-CoA hypothesis: low circulating citrate is not necessarily a marker of failing mitochondrial citrate production. The surgical example is almost the oppositeā€”the low plasma concentration appears to result from very rapid tissue uptake/utilization, particularly by liver. Conversely, profound hypothyroidism produces high plasma citrate despite impaired mitochondrial oxidative metabolism. This means serum citrate alone may be a poor proxy for mitochondrial citrate export or nuclear acetyl-CoA availability.

A potentially more informative next search would be for the lowest intracellular/tissue citrate concentrations reported in ageing or mitochondrial disease, because that is closer to the citrate ā†’ ACLY ā†’ nuclear acetyl-CoA question than serum citrate is.

#6

Direct-to-Consumer Options & Pricing

Even though you are buying it yourself, a licensed physician associated with the online service will review and approve the lab requisition behind the scenes. You then take that requisition form to a local Labcorp facility for the blood draw. [1, 2, 3, 4]

  • Online Health Platforms: Providers like DrSays offer the MVX Plus by NMR test for $72.99, plus a flat $9.99 blood collection fee. []
  • Holistic Health Centers: Because the MVX index is highly popularized by the alternative medicine community, practitioner groups like The Nutritional Healing Center offer direct mail-order requisitions for $49, while other clinics offer it for $79 to $89. [1, 2, 3]
  • State Restrictions: Note that direct-to-consumer lab ordering is restricted by law in certain states. You cannot use these third-party online ordering services if you live in New York, New Jersey, Rhode Island, Massachusetts, or Maryland. [1, 2]
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#7

Apparently, it is known that that numerical concentration across nmr platforms can vary. So that seems to explain that.

#8

It doesnā€™t explain the very low figures in the paper, but I am not inclined to spend any more time on this issue.

#9

Attia podcast aired yesterday with an 2+ hour interview of James Otvos, the scientist that led the development of the MVX. Besides the MVX test, a lot of info about lipids and testing labs. The MVX data presented certainly surprised (positively) Attia.

Iā€™m sold, and Iā€™ll be buying this test- hopefully from GoodLabs as I requested they add this test to their panels.

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#10

Agree. I found Attiaā€™s podcast exceptionally informative and worth a second review. I recommend it, Among other things, the podcast brought to mind @John_Hemmingā€™s discussions on citrate. Otvos is a first tier scientist who came at this topic (stumbled on it, really) from a unique perspective.

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#11

Own Your Labs has it for 49$, just ordered and took the test this week: Own Your Labs Ā· OYL

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#12

I ordered it from LabCorp, via the Nutritional Healing Center of Ann Arbor. Also $49. Glad you posted this. Some people may not want to know, but it provides actionable intelligence, as RapAdmin might say.

#13

So what IS the actionable intelligence for a high MVX? I donā€™t recall them talking about that in the podcast. Are there specific actions that can be taken to lower MVX itself, or just secondary things we can do to help mitigate the consequences?

#14

Serum citrate is rapidly converted by the liver into sodium bicarbonate. One molecule of citrate is normally converted into three molecules of bicarb. However, patients with liver damage have a lower conversion rate. How would you rate your liver, John Hemming?

#15

I have over 4 years of weekly liver markers and it has generally been quite good on the ALP/ALT/AST front (where good is normally lower). Here are the last few weeks:

ALP AST ALT
47 22.1 15.5
46 <18.7 <10
38 18.6 11.4
42 15.1 7.7
60 24 19
46 22 11
49 18.9 12
44 22.8 <10
50 23

I am not sure why this is relevant, however. Not all citrate is converted by the liver, some is excreted in urine, some is processed by cells. The citrate cellular membrane transporters in the SLC13 series are expressed by a wide range of cells.

The normal citrate serum figures are the normal ones.

I have written about the alkalinising effects of citrate in my BSRA 2026 poster

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image1082Ɨ1235 231 KB

#16

I take about six half-teaspoons of sodium citrate per day, which, as you say, has an alkalizing effect on the bodyā€™s pH. I have found it to be an excellent treatment for both acid reflux and metabolic acidosis. The liver is relevant because of the biomechanics.

#17

I accept that the liver processes some of the citrate into bicarbonate and that SLC13A5 is expressed strongly in the liver. However, I donā€™t understand where this is relevant to the odd results in the original paper.

#18

Just got results back from my first test. The summary:

  • overall inflammation is low
  • BCAA levels are in the upper range. I consume what people here would consider a ā€œhigh proteinā€ diet. I also lift weights.
  • adequate citrate levels indicate I have enough material for mitochindrial production.

Hereā€™s a more detailed AI summary:

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#19

Good numbers, though Iā€™m not surprised. Iā€™m sure you would rank high on the conscientiousness index. It might be helpful if you listed here, in one place, all your peptides, supplements, and other protocols, as well as your age, diet, and fitness routine, if that is not too much to ask.

#20

Current list:

  • Retatrutide 10mg weekly
  • rosuvastatin 10mg
  • Ezetimibe 10mg daily
  • vitamin D3 5000iu daily
  • tesamorelin 0.6mg daily (for TRIIM-X, will likely stop it in 6 months)
  • empagliflozin 10mg daily

Iā€™m in my 40s. My current diet is mostly high protein (meat, protein shakes) and high fiber (a lot of beans, vegetables, fruits). I used to be more disciplined in my diet, but because now Iā€™m satiated more easily by food, I can eat anything I want and not worry about eating too much.

These days I only work out only 3 times a week, but I do everything during those 3 sessions: lift weights and a cardio session right after. My lifting focus is mainly on lower body movements, and on doing unlilateral training. Unlilateral training helps me in 2 things: general balance, and ability to effectively lift more weights per limb.

Hereā€™s my old supplement list for comparison:

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