Visceral Fat vs Subcutaneous Fat: What Testing Can Show

Subcutaneous fat sits under the skin; visceral fat packs in around the organs. Only imaging can draw the line between the two. Bioimpedance body composition estimates muscle, fat and water and tracks your own numbers over time, which a scale cannot do.

Weight is the endpoint the fasting trials used, and it is the wrong one. The deep fat around your organs and the fat under your skin move independently, and only one of them behaves like an inflamed organ.

The visceral fat vs subcutaneous fat distinction is the one your bathroom scale cannot make, and it is the distinction that decides whether a change in how you eat did anything worth doing. Subcutaneous fat sits under the skin. Visceral fat packs in around the organs, and it is the compartment that behaves like an inflamed organ in its own right. A scale adds them together with muscle, water and last night’s dinner, then reports one number. The video Six Meals a Day Is a Business Model, from The Angry Gut by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes, makes the motility argument. This is the measuring one.

Visceral fat vs subcutaneous fat: which one comes off first?

Look at what happens when somebody images the compartments instead of weighing the person. Across a seven-day water-only fast in 12 volunteers, fat under the skin fell significantly while the visceral depot did not budge. When the depth of the fast became the randomized variable across 76 adults, alternate-day fasting reduced visceral fat mass and an eight-hour eating window did not, with energy intake down 34 percent in the deeper arm against 15 percent in the shallow one. The deep compartment answers to depth. A shallow schedule never reaches it, and a scale cannot tell you which one you got.

There is a second reason weight misleads. In a supervised ten-day fast, most of what came off was lean tissue, not fat. After the seven-day fast, lean mass moved from a loss of 3.6 kilograms to a loss of 0.69 within three days of eating again, while the fat loss held. So the number on the scale during a long gap is mostly reporting water and muscle, and it gives back much of what it took as soon as food returns.

What does a bioimpedance body composition test measure?

Measura [Cardiometabolic and Autonomic Health Analysis] measures bioimpedance body composition, which estimates the compartments — muscle, fat and water — by passing a small current through the body. Be clear about what that is and is not. It is an estimate of compartments, not a picture of them. It is not imaging, and it cannot draw the line between visceral and subcutaneous fat the way a scan can. Imaging is a different test, ordered elsewhere by your physician. What bioimpedance does well is track your own muscle and fat over time, which is the thing a scale hides and the thing most likely to be moving in the wrong direction while the weight stays flat.

How do you measure your metabolic rate?

Indirect calorimetry measures your resting metabolic rate from the oxygen you use and the carbon dioxide you make, rather than predicting it from an equation built on other people. If you have been told your metabolism is broken, or that skipping meals broke it, that is the measurement that settles the argument in your own body. Laboratory panels then put numbers on the metabolic and inflammatory terrain, the metaflammation that keeps insulin high and fat locked in storage. Results go to your physician; Measura measures and does not treat.

Why start there rather than with a diet? Because being metabolically healthy is now unusual, and the terrain is what decides whether fat can leave storage at all. Fewer than 12.2 percent of US adults met the standard on NHANES 2009 to 2016, and fewer than 7 percent under the stricter post-2021 criteria. Among the patients who come through our own doors it is under 3 percent overall and under 1 percent of those living with chronic pain — practice-reported figures from our own population, not trial outcomes, and individual results vary. The first brain sits inside that terrain, which is why the gut and the metabolism are one conversation rather than two.

Is eating six small meals a day better than three?

The strongest version of the grazing argument is that frequent small meals keep the furnace stoked. It was tested in a metabolic chamber, a sealed room that measures every breath: three meals a day against six produced the same 24-hour energy expenditure and the same fat oxidation, 82 against 80 grams a day. Hunger was the one thing that climbed on the six-meal days. Among adults with type 2 diabetes eating identical calories and macronutrients, two meals a day beat six, with 3.7 kilograms lost against 2.3 and a greater fall in liver fat. Grazing advice did not arrive from nowhere either; an industry built on between-meal eating needs mouths that rarely close. Name the incentive, not a villain.

So the useful endpoints are the compartments and the numbers, not the schedule. Two people can eat the same way for three months and have opposite results in muscle, fat and insulin, and only one of them will find that out.

Before you change anything

Two cautions, and they are not decoration. If you take any medication that lowers blood sugar or blood pressure, do not start fasting or lengthen your overnight gap without talking to the physician who prescribes it; a fast changes what those drugs do to you, and in one study the need for blood pressure medication fell months afterward. And a fast is a dose. Among 2,762 young people, 47.7 percent of the women reported intermittent fasting within the year, and the practice tracked with eating-disorder psychopathology. If food has ever been a battleground for you, that history belongs in the conversation before any schedule does.

Ask for the measurements first: body composition, a measured resting metabolic rate, and laboratory markers of insulin and inflammation. Then repeat them, because a single reading is a dot and you need a line. Background on the numbers is in metabolic rate and energy, and every study named here with its full figures and limits sits in the companion deep dive for The Angry Gut. The testing side of the previous chapter is what a gut microbiome test cannot measure, and clinicians will want the version written for physicians. The same visceral depot sits behind a share of cancer risk, discussed in whether obesity causes cancer.

Frequently asked questions

References

• Pietzner, M., Uluvar, B., Kolnes, K. J., Jeppesen, P. B., Frivold, S. V., Skattebo, Ø., Johansen, E. I., Skålhegg, B. S., Wojtaszewski, J. F. P., Kolnes, A. J., Yeo, G. S. H., O’Rahilly, S., Jensen, J., & Langenberg, C. (2024). Systemic proteome adaptions to 7-day complete caloric restriction in humans. Nature Metabolism, 6(4), 764-777. https://doi.org/10.1038/s42255-024-01008-9
• Derron, N., Güntner, A. T., Weber, I. C., Braun, J., Koska, İ. Ö., Othman, A., Mönch, L., von Eckardstein, A., Puhan, M. A., Beuschlein, F., Hochuli, M., Zamboni, N., Guggenberger, R., & Gerber, P. A. (2025). Alternate-day fasting elicits larger changes in fat mass than time-restricted eating in adults without obesity – A randomized clinical trial. Clinical Nutrition, 53, 212-221. https://doi.org/10.1016/j.clnu.2025.08.033
• Ohkawara, K., Cornier, M.-A., Kohrt, W. M., & Melanson, E. L. (2013). Effects of increased meal frequency on fat oxidation and perceived hunger. Obesity, 21(2), 336-343. https://doi.org/10.1002/oby.20032
• Kahleova, H., Belinova, L., Malinska, H., Oliyarnyk, O., Trnovska, J., Skop, V., Kazdova, L., Dezortova, M., Hajek, M., Tura, A., Hill, M., & Pelikanova, T. (2014). Eating two larger meals a day (breakfast and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients with type 2 diabetes: A randomised crossover study. Diabetologia, 57(8), 1552-1560. https://doi.org/10.1007/s00125-014-3253-5
• Laurens, C., Grundler, F., Damiot, A., Chery, I., Le Maho, A.-L., Zahariev, A., Le Maho, Y., Bergouignan, A., Gauquelin-Koch, G., Simon, C., Blanc, S., & Wilhelmi de Toledo, F. (2021). Is muscle and protein loss relevant in long-term fasting in healthy men? A prospective trial on physiological adaptations. Journal of Cachexia, Sarcopenia and Muscle, 12(6), 1690-1703. https://doi.org/10.1002/jcsm.12766
• Ganson, K. T., Cuccolo, K., Hallward, L., & Nagata, J. M. (2022). Intermittent fasting: Describing engagement and associations with eating disorder behaviors and psychopathology among Canadian adolescents and young adults. Eating Behaviors, 47, 101681. https://doi.org/10.1016/j.eatbeh.2022.101681
• Maifeld, A., Bartolomaeus, H., Löber, U., Avery, E. G., Steckhan, N., Markó, L., Wilck, N., Hamad, I., Šušnjar, U., Mähler, A., Hohmann, C., Chen, C.-Y., Cramer, H., Dobos, G., Lesker, T. R., Strowig, T., Dechend, R., Bzdok, D., Kleinewietfeld, M., … Forslund, S. K. (2021). Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. Nature Communications, 12(1), 1970. https://doi.org/10.1038/s41467-021-22097-0

Related reading

• Gut Microbiome Test Results: What They Cannot Measure
• Long-Term PPI Use: What Your Blood Work and Body Can Show
• Bioimpedance Body Composition

How to Measure Visceral Fat When the Scale Says You’re Fine

Visceral fat is imaged directly on CT or MRI. Bioimpedance body composition separates fat mass from lean mass, and blood work such as fasting glucose, insulin, lipids and liver enzymes shows what the depot is doing downstream; weight and body mass index cannot locate it.

Your weight and body mass index cannot show where your fat sits or whether it has turned into immune tissue. Location predicts the harm, and location has to be measured.

Knowing how to measure visceral fat matters more than knowing what you weigh, because the fat packed around your intestines and liver behaves like an immune organ, and it can be inflamed in a person whose scale reading looks ordinary. In the video Your Immune System Is Not Confused, from The Angry Gut by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes, that fat is one part of a larger argument about Crohn’s disease and a chronic immune load. Here the question is narrower and practical: what would show that load in you, what a routine visit checks, and what it leaves out.

Why doesn’t a normal weight rule out visceral fat?

For years I told people with borderline blood sugar that their numbers were not too bad, and a normal weight made that sentence easier to say. It was the wrong reassurance. Weight is a total. It says nothing about where fat is stored or what the cells inside it are doing.

In the fat of lean mice and lean humans, macrophages, the immune system’s cleanup cells, make up under 10% of the cells. In the most obese mice they pass 50%. In people, the better predictor of that crowding was not body mass index but the size of the individual fat cells, at r² = 0.86 against 0.43 for body mass index. Swollen fat cells are the ones that struggle first, and resident immune cells arrive to help. That help becomes a steady inflammatory signal: more than 90% of what fat tissue releases, apart from the hormones adiponectin and leptin, comes from the immune and support cells living in it, not from the fat cells.

What makes visceral fat dangerous?

In people with obesity, the omental fat that hangs inside the abdomen carried twice as many macrophages as fat under the skin, and that omental burden tracked fasting glucose, insulin sensitivity and liver injury. This fat drains through the portal vein to the liver. In severely obese adults sampled during bariatric surgery, portal blood carried about 50% more interleukin-6, an inflammatory messenger, than arterial blood. Your liver gets the first and strongest dose.

The pattern holds when weight is taken out of the picture. In omental biopsies from women having endometrial cancer surgery, dying fat cells surrounded by macrophages were found in 48% of samples, and they went with diabetes rather than body mass index. In an imaging cohort of 3,086 adults with a mean age of 50.2, more visceral fat meant higher risk of heart and blood vessel disease (hazard ratio 1.44) and of cancer (1.43), and that held even with body mass index accounted for. South Asians carry more visceral fat and less thigh muscle for their body size. A person of normal weight with disproportionate visceral fat is not lean, whatever the chart says.

None of this is a character flaw. Agricultural subsidies make refined carbohydrate and industrial seed oil the cheapest food on the shelf, your first brain, the gut, absorbs the surplus, and the overflow is stored on the road leading out of it, where metaflammation starts.

What does visceral fat have to do with Crohn’s disease?

In Crohn’s disease, fat can wrap the inflamed intestine. Researchers cultured live bacteria from the mesenteric fat of 9 of 11 people with Crohn’s disease, and also from 4 of 4 healthy controls, so bacteria in that fat are expected; the fat is placed to meet them. What differed in Crohn’s was which organisms arrived.

Be clear about the limits. Measura [Cardiometabolic and Autonomic Health Analysis] does not diagnose Crohn’s disease and does not monitor it. It does not replace calprotectin, endoscopy or your gastroenterologist’s plan, which are done elsewhere. If you take a biologic, nothing here is a reason to stop it. Loss of response to anti-TNF drugs runs at about 20.9% per patient-year, so the question is what gets measured and repaired while the drug holds. Measura can add the metabolic picture under the disease, the one nobody on the immune side is charting.

How do you measure visceral fat, and what does each method show?

• Weight and body mass index. A total and a ratio. They cannot locate fat or see muscle, and they are where most visits stop.
• CT or MRI. Imaging sees the visceral compartment directly and was the method behind the cohort above. It is done elsewhere, usually for another reason. If you have had a scan, ask whether the report described visceral fat.
• Body composition. Bioimpedance body composition sends a small, painless electrical signal through the body to estimate fat mass and lean mass separately, so muscle and fat stop hiding inside one number. It is an estimate rather than an image, and its strength is the pattern and the trend across repeat visits.
• Blood work. Laboratory panels show what the depot is doing downstream: fasting glucose and insulin, lipids, liver enzymes and inflammatory markers, the same kinds of values the omental burden tracked in surgical patients.

The non-obvious point is that quieting the signal does not change the depot. In 56 people with metabolic syndrome, the drug etanercept cut C-reactive protein sharply over four weeks, yet body composition and insulin sensitivity did not budge. A lower inflammation number is not a smaller visceral compartment, which is why composition and metabolic labs are worth tracking together. Unmeasured is unmanaged.

What should you ask your doctor about visceral fat?

• Ask which fat has ever been measured, or whether weight is standing in for it. The difference is laid out in body composition, not BMI.
• Ask for fasting insulin alongside glucose. Glucose can stay normal while insulin works harder to hold it there; see insulin resistance and metabolic health.
• If you are South Asian, or diabetes runs in your family, say so at the start of the visit.
• If you have Crohn’s disease, ask who is responsible for your metabolic terrain while the biologic holds the bowel still.
• Ask whether a repeat body composition test can show a trend rather than a single snapshot.

Results go to your physician, who decides what they mean for your care. The book companion, the deep dive on the immune matrix, lists every study above with its limits. Sleep and schedule sit on top of this same terrain, covered in night shift health risks you can measure. In MRI data from more than thirty thousand adults, the same visceral depot tracked how many places hurt, covered in whether belly fat can cause chronic pain.

Frequently asked questions

References

• Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003). Obesity is associated with macrophage accumulation in adipose tissue. The Journal of Clinical Investigation, 112(12), 1796-1808. https://doi.org/10.1172/JCI19246
• Cancello, R., Tordjman, J., Poitou, C., Guilhem, G., Bouillot, J. L., Hugol, D., Coussieu, C., Basdevant, A., Bar Hen, A., Bedossa, P., Guerre-Millo, M., & Clement, K. (2006). Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes, 55(6), 1554-1561. https://doi.org/10.2337/db06-0133
• Fontana, L., Eagon, J. C., Trujillo, M. E., Scherer, P. E., & Klein, S. (2007). Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes, 56(4), 1010-1013. https://doi.org/10.2337/db06-1656
• van den Bosch, A. A. S., Kooreman, L., van de Weijer, T., Romano, A., Brecheisen, R., Jin, X., Delvoux, B., Kruitwagen, R. F. P. M., Pijnenborg, J. M. A., & Werner, H. M. J. (2026). Visceral adipose tissue inflammation in endometrial cancer. Cancer Treatment and Research Communications, 48, 101273. https://doi.org/10.1016/j.ctarc.2026.101273
• Britton, K. A., Massaro, J. M., Murabito, J. M., Kreger, B. E., Hoffmann, U., & Fox, C. S. (2013). Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. Journal of the American College of Cardiology, 62(10), 921-925. https://doi.org/10.1016/j.jacc.2013.06.027
• Eastwood, S. V., Tillin, T., Wright, A., Mayet, J., Godsland, I., Forouhi, N. G., Whincup, P., Hughes, A. D., & Chaturvedi, N. (2014). Thigh fat and muscle each contribute to excess cardiometabolic risk in South Asians, independent of visceral adipose tissue. Obesity (Silver Spring, Md.), 22(9), 2071-2079. https://doi.org/10.1002/oby.20796
• Ha, C. W. Y., Martin, A., Sepich-Poore, G. D., Shi, B., Wang, Y., Gouin, K., Humphrey, G., Sanders, K., Ratnayake, Y., Chan, K. S. L., Hendrick, G., Caldera, J. R., Arias, C., Moskowitz, J. E., Ho Sui, S. J., Yang, S., Underhill, D., Brady, M. J., Knott, S., … Devkota, S. (2020). Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans. Cell, 183(3), 666-683.e17. https://doi.org/10.1016/j.cell.2020.09.009
• Qiu, Y., Chen, B.-L., Mao, R., Zhang, S.-H., He, Y., Zeng, Z.-R., Ben-Horin, S., & Chen, M.-H. (2017). Systematic review with meta-analysis: Loss of response and requirement of anti-TNFα dose intensification in Crohn’s disease. Journal of Gastroenterology, 52(5), 535-554. https://doi.org/10.1007/s00535-017-1324-3
• Fain, J. N., Madan, A. K., Hiler, M. L., Cheema, P., & Bahouth, S. W. (2004). Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology, 145(5), 2273-2282. https://doi.org/10.1210/en.2003-1336
• Bernstein, L. E., Berry, J., Kim, S., Canavan, B., & Grinspoon, S. K. (2006). Effects of etanercept in patients with the metabolic syndrome. Archives of Internal Medicine, 166(8), 902-908. https://doi.org/10.1001/archinte.166.8.902

Related reading

• Emulsifiers in Food: What No Test Can Measure About You
• Night Shift Health Risks You Can Actually Measure
• Bioimpedance Body Composition

Emulsifiers in Food: What No Test Can Measure About You

Emulsifiers in food reach you as a mixture of lecithins, mono- and diglycerides, carrageenan and phosphates, eaten several times a day for years, and no test in ordinary practice measures how much of it you have eaten.

Your macros can be fine while your microbes only ever see the ingredient list. Nothing sold as a test can measure that exposure, which makes the next question what can be measured.

Emulsifiers in food are the second diet most people are eating without knowing it. The first diet is the one on the nutrition label, where the calories and the protein look reasonable. The second is the ingredient list underneath, and your bacteria are the ones reading it.

The video Your Microbes Read the Label, Not the Macros follows a woman of forty-one whose week of food photographs would pass any dietitian’s review, until the labels were read aloud. It belongs to The Angry Gut, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes. Measura [Cardiometabolic and Autonomic Health Analysis] is a testing service, and no test in its library measures what additives you have eaten, because no such measurement exists in ordinary practice.

Emulsifiers in food are a mixture, not a chemical

Among 106,489 French adults, forty-eight additives were eaten by more than 10% of people surveyed. Lecithins reached 86.6% of consumers, mono- and diglycerides of fatty acids 78.1%, carrageenan 77.5%, and the phosphate group 70.1%. People did not meet these compounds one at a time either; they arrived in recognizable clusters, several times a day, for years.

That matters for anyone hunting a single culprit. The compound most of the laboratory work studies is carboxymethylcellulose, sold on labels as cellulose gum. It is not the exposure. The exposure is the whole cluster, eaten by a body nobody asked.

The wall these compounds meet is thinner than advertised

Before anything can be said to strip a gut lining, someone has to measure the lining. The figures in wide circulation, around 830 microns of colonic mucus gel with roughly 116 microns firmly attached, were measured in rats. Human sigmoid biopsies gave a mean inner mucus thickness of 19.4 microns, with a standard deviation of 9.9 and a range from 6.2 to 45.6.

Two honest caveats come with those human numbers. The loose outer layer was missing from every biopsy, because bowel preparation washes it away in 96% of prepared subjects, and in paired animal samples the choice of preservative alone changed the measured thickness. Every human mucus number came out of a specimen jar. The wall is real; it is also a fraction of the number people quote, and it is the surface your first brain keeps between itself and everything you swallow, while the second brain in your skull never meets any of it.

How do emulsifiers affect gut bacteria?

Dr. Padda explained this the easy way for years: emulsifiers are detergents, dish soap on the lining. He now says that version was half right and it was the wrong half. In mice raised with no gut bacteria at all, neither compound thinned the mucus, and beads the size of bacteria stayed as far from the tissue as they had started. In animals carrying only a small defined set of bacteria, nothing happened either.

Grow a human microbial community outside a body, add cellulose gum, and its inflammatory potential rises while the roster of species present does not significantly change. Read that twice, because it decides what testing can see. The population held still and the behavior changed, so a stool census would have reported that nothing happened. When twenty common emulsifiers were screened this way, the starkest damage came from the carrageenans and the gums, two of which were on that patient’s labels.

What happened when healthy people ate an emulsifier?

Only one randomized trial has fed a purified emulsifier to healthy humans. Its sixteen adults spent eleven days on a diet stripped of other emulsifiers, with 15 g of cellulose gum a day added for seven of them. The distance between bacteria and the intestinal wall, the measure the trial was built to detect, did not change. Encroachment turned up in 2 of 7 treated volunteers and 0 of 9 controls. What did move was the composition of the microbiota, the chemistry of the stool, and abdominal discomfort after meals.

That is a modest result, and the reason matters more than the verdict. One additive, on a background diet scrubbed of the rest, in metabolically healthy volunteers, for eleven days. Trials remove the complicated patient to get a clean answer, and the complicated patient is the one reading labels in the kitchen.

What can a test measure instead of emulsifiers?

There is a real measurement in this literature, and it is about the body rather than the shelf. In 42 people having colonoscopy, people with type 2 diabetes had their bacteria sitting almost 3-fold closer to the nearest lining cell. It tracked hemoglobin A1c at an r-squared of 0.51 and fasting glucose at 0.46, but body mass index only at 0.16. Obesity by itself did nothing, and removing the subjects with diabetes erased the difference entirely.

The wall tracked blood sugar, not waist size. That is why the useful tests here measure metabolic state:

• Laboratory panels put current numbers on blood sugar, lipids and inflammatory markers, which is where metaflammation stops being a word and becomes a result.
• Bioimpedance body composition separates fat from muscle, which matters because body mass index was the weakest of the three measures above.

Neither test measures additives, mucus or bacteria, and neither diagnoses a gut disease. They describe the state your body is in while it meets that mixture daily, and the findings go to your physician. Good metabolic health is rare: under 12.2% of adults on NHANES 2009-2016, and under 7% on the tighter post-2021 criteria.

How can you cut back on emulsifiers?

The prescription is shorter than the science. Fewer items with ingredient lists, more items with none. People can actually do this, and somebody measured it: in stable Crohn’s disease, a low-emulsifier diet cut the frequency of additive-carrying foods by 94.6%.

• Read your own labels for a week before changing anything, and count how many distinct additives you meet in a day.
• Remember that engineered food does two things at once. It adds the compounds and removes the fermentable fiber, and in mice deprived of fiber the mucus layer thinned five- to six-fold while the bacteria turned on the wall itself for food.
• Expect the calories to argue back. Twenty adults fed matched macronutrients ate 508 kcal a day more on the ultra-processed menu and gained weight on it, while losing weight on the unprocessed one.
• Do not stop a prescribed medication or a therapeutic diet on your own. Bring any restriction plan to your own physician first.

The full trial numbers, including what each study could not show, sit in the book’s Deep Dive companion. The fuel those same bacteria are supposed to be making is covered in what a flagged butyrate result really samples, and the metabolic pattern behind the wall measurement above is in what insulin resistance looks like before diabetes.

Frequently asked questions

References

• Chazelas, E., Druesne-Pecollo, N., Esseddik, Y., de Edelenyi, F. S., Agaesse, C., De Sa, A., Lutchia, R., Rebouillat, P., Srour, B., Debras, C., Wendeu-Foyet, G., Huybrechts, I., Pierre, F., Coumoul, X., Julia, C., Kesse-Guyot, E., Alles, B., Galan, P., Hercberg, S., … Touvier, M. (2021). Exposure to food additive mixtures in 106,000 French adults from the NutriNet-Sante cohort. Scientific Reports, 11(1), 19680. https://doi.org/10.1038/s41598-021-98496-6
• Jawhara, M., Sorensen, S. B., Heitmann, B. L., Halldorsson, T. I., Pedersen, A. K., & Andersen, V. (2020). The relation between red meat and whole-grain intake and the colonic mucosal barrier: A cross-sectional study. Nutrients, 12(6), 1765. https://doi.org/10.3390/nu12061765
• Chassaing, B., Raja, S. M., Lewis, J. D., Srinivasan, S., & Gewirtz, A. T. (2017a). Colonic microbiota encroachment correlates with dysglycemia in humans. Cellular and Molecular Gastroenterology and Hepatology, 4(2), 205-221. https://doi.org/10.1016/j.jcmgh.2017.04.001
• Chassaing, B., Van de Wiele, T., De Bodt, J., Marzorati, M., & Gewirtz, A. T. (2017b). Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut, 66(8), 1414-1427. https://doi.org/10.1136/gutjnl-2016-313099
• Chassaing, B., Compher, C., Bonhomme, B., Liu, Q., Tian, Y., Walters, W., Nessel, L., Delaroque, C., Hao, F., Gershuni, V., Chau, L., Ni, J., Bewtra, M., Albenberg, L., Bretin, A., McKeever, L., Ley, R. E., Patterson, A. D., Wu, G. D., … Lewis, J. D. (2022). Randomized controlled-feeding study of dietary emulsifier carboxymethylcellulose reveals detrimental impacts on the gut microbiota and metabolome. Gastroenterology, 162(3), 743-756. https://doi.org/10.1053/j.gastro.2021.11.006
• Chassaing, B., Koren, O., Goodrich, J. K., Poole, A. C., Srinivasan, S., Ley, R. E., & Gewirtz, A. T. (2015). Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature, 519(7541), 92-96. https://doi.org/10.1038/nature14232
• Hall, K. D., Ayuketah, A., Brychta, R., Cai, H., Cassimatis, T., Chen, K. Y., Chung, S. T., Costa, E., Courville, A., Darcey, V., Fletcher, L. A., Forde, C. G., Gharib, A. M., Guo, J., Howard, R., Joseph, P. V., McGehee, S., Ouwerkerk, R., Raisinger, K., … Zhou, M. (2019). Ultra-processed diets cause excess calorie intake and weight gain: An inpatient randomized controlled trial of ad libitum food intake. Cell Metabolism, 30(1), 67-77.e3. https://doi.org/10.1016/j.cmet.2019.05.008
• Desai, M. S., Seekatz, A. M., Koropatkin, N. M., Kamada, N., Hickey, C. A., Wolter, M., Pudlo, N. A., Kitamoto, S., Terrapon, N., Muller, A., Young, V. B., Henrissat, B., Wilmes, P., Stappenbeck, T. S., Nunez, G., & Martens, E. C. (2016). A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell, 167(5), 1339-1353.e21. https://doi.org/10.1016/j.cell.2016.10.043
• Salame, C., Javaux, G., Sellem, L., Viennois, E., de Edelenyi, F. S., Agaesse, C., De Sa, A., Huybrechts, I., Pierre, F., Coumoul, X., Julia, C., Kesse-Guyot, E., Alles, B., Fezeu, L. K., Hercberg, S., Deschasaux-Tanguy, M., Cosson, E., Tatulashvili, S., Chassaing, B., … Touvier, M. (2024). Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Sante prospective cohort study. The Lancet Diabetes & Endocrinology, 12(5), 339-349. https://doi.org/10.1016/S2213-8587(24)00086-X

Related reading

• Butyrate Deficiency Symptoms and What a Stool Test Really Shows
• How to Measure Visceral Fat When the Scale Says You’re Fine
• Laboratory Panels

Leaky Blood-Brain Barrier: The Body Numbers That Predict It Early

A leaky blood-brain barrier is predicted early by ordinary body numbers: among initially healthy older adults, a larger body mass index and a higher waist-to-hip ratio went with a leaking barrier two decades on, and in 1,015 people the leak followed diabetes rather than amyloid.

No office test can see the seal around your brain’s blood vessels. The forces that pry it open, though, show up in numbers most memory visits never collect.

Researchers can now watch contrast dye seep out of the smallest brain blood vessels in living people, and the first region to show it is the hippocampus, where new memories are filed. A leaky blood-brain barrier sounds like something only a research scanner could find. What predicts it is far more ordinary. Among older adults who were healthy at the start, heavier bodies and wider waists relative to hips foretold a leaking barrier twenty years on.

That thread runs through the video A Waistline Predicted a Leaking Brain, drawn from The Angry Gut by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes. Measura [Cardiometabolic and Autonomic Health Analysis] is a testing service. It measures; your physician interprets and treats. So the question here is narrow. If nobody can check the barrier at an ordinary appointment, which of the forces behind it can be put on paper?

What is a leaky blood-brain barrier?

The blood-brain barrier is the tightly sealed lining of the brain’s capillaries. It decides what passes from your bloodstream into brain tissue. Dr. Padda admits he once sketched it for trainees as a solid row of bricks, and living-patient imaging retired that sketch. With dynamic contrast MRI, older adults whose memory still tested normal showed permeability 41% higher in the hippocampus than young controls, and 107% higher in one of its subfields. In mild cognitive impairment, those regions rose further, by 24%, 53% and 27%, compared with age-matched peers.

The book gives this a precise vocabulary. The gut is the first brain. The organ in your skull is the second brain. The barrier is one of the borders between them, and what crosses it is best described as traffic: bacterial products and immune signals. A colony of bacteria living in a healthy brain has not been shown, and the most carefully controlled laboratory work argues against one.

Does a leaky blood-brain barrier show up before symptoms?

This is the finding that should change how you read a normal lab report. Among the volunteers with a leaking hippocampus, researchers also sampled spinal fluid, looking for familiar inflammatory messengers such as interleukin-6 and tumor necrosis factor. None had budged. Two things had: a marker of injury to pericytes, the cells that keep the barrier’s seams closed, which was up 115% in mild impairment, and the spinal fluid albumin ratio, up 30%.

A follow-up study of 161 people found no difference between impaired and unimpaired groups across 20 markers of inflammation and nerve degeneration, while the barrier measure still predicted who was impaired. The door opens first; inflammation shows up later. A clean inflammation panel does not prove the seal is intact.

What causes a leaky blood-brain barrier?

An older method compares albumin in spinal fluid with albumin in blood. Across 1,015 people, that ratio did not change in early Alzheimer’s disease and did not follow amyloid imaging or the APOE gene. It followed diabetes, and it rose alongside proteins that a strained blood-vessel lining sheds. A separate small study of type 2 diabetes found brain permeability already elevated before any vessel damage appeared on a conventional scan, and recent blood sugar control explained none of it.

Two biological drivers run through that record. One is years of high insulin and glucose load, the engine of metaflammation. The other is a vessel lining worn thin by that load. The third driver is not biological at all: a food supply engineered and subsidized to grow waistlines puts the problem in the pantry decades before it reaches a neurology office. The care system then splits the evidence. Your bowel belongs to one specialist, your memory to another, and your waist measurement to nobody.

What a routine memory visit records, and what it skips

A first visit for a memory complaint usually means a short screening test and a look at your medication list, sometimes followed by a brain scan. A borderline score often ends with advice to return in a year. What rarely gets written down are the numbers the barrier research keeps pointing toward: how much of your weight is fat, your fasting insulin, and whether either has drifted over a decade.

Be clear about the limit. Measura does not image the brain and does not measure barrier permeability. No office test does. That work belongs to research scanners and spinal fluid studies, and those two methods do not always agree with each other. What can be measured is the terrain those studies connect to the leak.

The measurements that close the gap

• Bioimpedance body composition estimates how much of you is fat mass and how much is lean tissue. A bathroom scale and a body mass index chart cannot separate the two, and the barrier cohorts pointed at body shape, not weight alone.
• Laboratory panels put numbers on the metabolic side, such as fasting insulin and blood sugar markers, so the insulin load is measured rather than assumed.
• Arterial stiffness and endothelial function testing looks at how rigid your arteries are and how the vessel lining responds. It does not examine brain vessels, but the leak tracked vessel-lining strain, which makes your body’s own arteries a reasonable place to look.
• Cognitive assessment gives memory, attention and processing speed a recorded baseline, so a borderline result becomes a starting line instead of a waiting period.

The brain-fuel side of memory is covered in what a normal blood sugar test can miss, and the reason a first score matters is laid out in what a cognitive baseline is for. Every result goes to your physician, who decides what it means for you. None of it is a reason to start or stop a medication on your own.

What to bring to your next appointment

The woman at the center of the video lived with bowel trouble for sixteen years before she ever raised a memory concern. Her sequence is worth copying as a habit.

1. The year your bowel habits changed and the year your memory did. Years, not decades.
2. Your waist measurement and weight history, and whether either moved in the last ten years.
3. A request to check fasting insulin during the same visit as the memory complaint.
4. A question about body composition, since two people at the same weight can carry very different amounts of fat.

The levers that move these numbers are food, meal timing, sleep and movement. No trial has yet shown that shrinking a waist narrows hippocampal leakage; the argument rests on mechanism and long cohorts, and acting on it does not have to wait. Every study with its limits is in the Chapter 12 Deep Dive. Clinicians can read the physician version of this screening question, and the next piece follows what fear does to digestion, measured.

Frequently asked questions

References

• Montagne, A., Barnes, S. R., Sweeney, M. D., Halliday, M. R., Sagare, A. P., Zhao, Z., Toga, A. W., Jacobs, R. E., Liu, C. Y., Amezcua, L., Harrington, M. G., Chui, H. C., Law, M., & Zlokovic, B. V. (2015). Blood-brain barrier breakdown in the aging human hippocampus. Neuron, 85(2), 296-302. https://doi.org/10.1016/j.neuron.2014.12.032
• Nation, D. A., Sweeney, M. D., Montagne, A., Sagare, A. P., D’Orazio, L. M., Pachicano, M., Sepehrband, F., Nelson, A. R., Buennagel, D. P., Harrington, M. G., Benzinger, T. L. S., Fagan, A. M., Ringman, J. M., Schneider, L. S., Morris, J. C., Chui, H. C., Law, M., Toga, A. W., & Zlokovic, B. V. (2019). Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nature Medicine, 25(2), 270-276. https://doi.org/10.1038/s41591-018-0297-y
• Janelidze, S., Hertze, J., Nägga, K., Nilsson, K., Nilsson, C., Wennström, M., van Westen, D., Blennow, K., Zetterberg, H., & Hansson, O. (2017). Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype. Neurobiology of Aging, 51, 104-112. https://doi.org/10.1016/j.neurobiolaging.2016.11.017
• Chen, Y. C., Lu, B. Z., Shu, Y. C., & Sun, Y. T. (2022). Spatiotemporal dynamics of cerebral vascular permeability in type 2 diabetes-related cerebral microangiopathy. Frontiers in Endocrinology, 12, 805637. https://doi.org/10.3389/fendo.2021.805637
• Bedarf, J. R., Beraza, N., Khazneh, H., Ozkurt, E., Baker, D., Borger, V., Wullner, U., & Hildebrand, F. (2021). Much ado about nothing? Off-target amplification can lead to false-positive bacterial brain microbiome detection in healthy and Parkinson’s disease individuals. Microbiome, 9(1), 75. https://doi.org/10.1186/s40168-021-01012-1

Related reading

• Crohn’s Disease Back Pain: What Scans Miss and What to Measure
• Can Stress Cause Stomach Problems? What Your Nervous System Shows
• Bioimpedance Body Composition

Crohn’s Disease Back Pain: What Scans Miss and What to Measure

Crohn’s disease can cause back pain, largely through inflammation. Across 71 pooled studies of inflammatory bowel disease, about 10% of people had sacroiliitis, inflammation where the spine meets the pelvis, and 3% had ankylosing spondylitis; the pain tends to follow an inflammatory pattern rather than a mechanical one.

Back pain in someone with Crohn’s disease or colitis is usually scanned as a mechanical problem. The inflammatory pattern that points back to the bowel lives in the history, not the MRI.

Crohn’s disease back pain often gets the same workup as anyone’s back pain: an MRI, physical therapy, perhaps an injection. The scans come back showing wear that most adults carry, and the bowel diagnosis sitting in the same chart never enters the conversation.

The video above, Your Gut Is Reaching Your Spine, is Chapter 11 of The Angry Gut by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes. It follows a man whose colitis and eleven years of back pain were never discussed together. The question here is about measurement: what shows bowel inflammation reaching the spine, what a Measura [Cardiometabolic and Autonomic Health Analysis] visit cannot show, and what it can.

How often does Crohn’s disease affect the spine?

This part is not a theory. Across 71 pooled studies of people with inflammatory bowel disease, about 10% had sacroiliitis, inflammation where the spine meets the pelvis, 3% had ankylosing spondylitis and 13% had arthritis in the limbs. When researchers combined 52 studies covering 352,454 patients, roughly a quarter (24%) had some complication beyond the bowel; the share was 35% in Crohn’s disease and 27% in ulcerative colitis.

Genes sort the risk. In ulcerative colitis, people carrying the HLA-B27 gene had a relative risk of 22.17 for developing ankylosing spondylitis. Rats engineered to carry that human gene develop gut and joint inflammation, but animals raised with no bacteria at all developed neither. That is animal work, a proof of principle, and it says the bacteria of the first brain are needed for the joint disease in a susceptible body.

What does Crohn’s back pain feel like?

Inflammatory back pain has a signature, and it is found by asking, not imaging. Pain that wakes you in the second half of the night. Morning stiffness lasting longer than half an hour. Pain that eases when you move and worsens when you rest, which is backward for a mechanical back. And the question almost nobody asks: has anyone linked it to your bowel?

Meanwhile the MRI is crowded with findings that do not sort people. A Modic change, a signal change in the bone beside a disc, turns up in roughly 6% of people without pain, against a median 43% among people who hurt. Type 1 raised the odds of back pain about fourfold (4.01); a Modic change of unstated type came in at 1.62, an estimate that includes no effect at all. A scan shows where the spine has changed. It rarely tells anyone why it hurts.

What Measura does not measure

Be clear about the limits. Measura does not do imaging, so there is no MRI or X-ray of the sacroiliac joints. It does not do colonoscopy, stool testing or microbiome sequencing. It does not run genetic tests such as HLA-B27. Those belong to your physician, a gastroenterologist or a rheumatologist, ordered elsewhere. Anyone offering to read your bowel’s effect on your spine from one stool census is selling more certainty than the science holds.

What Measura can show in the same person

What a testing visit adds is the terrain the inflammation lives in. Laboratory panels capture metabolic blood work that can reflect insulin resistance and metaflammation, the slow-burning inflammation of metabolic disease. Bioimpedance body composition separates fat from muscle, compartments a bathroom scale lumps together. Heart rate variability measures the beat-to-beat variation that reflects how the autonomic nervous system balances stress and recovery, which matters in someone whose pain breaks up sleep night after night.

None of those numbers diagnoses spinal arthritis. They answer a different question: how hot the terrain is running while specialists look at separate organs. For how insulin resistance ties into long-running pain, see chronic pain and metabolic health; for sleep, heart rhythm and related complaints, see autonomic symptoms.

Do bacteria in the spinal disc cause back pain?

Sequencing has found bacterial DNA in nearly every disc tested, even in donor discs that looked normal on MRI, which retires the idea that discs are sterile. Whether those bacteria cause pain is a separate matter. A disc has no blood supply, so a pill barely reaches it. In a large antibiotic trial for back pain with Modic changes, the researchers’ own bar for a meaningful change was 4 points; the result was 1.6, and drug-related side effects ran 56% against 34%. A 2026 trial of the same drug found adverse events in 40.0% of people taking it and 23.5% on placebo, without a pain benefit at twelve months.

Do not start antibiotics on your own for back pain. What is established is inflammation traveling from bowel to spine, so getting the bowel disease under control is part of caring for the back.

The first brain end of the problem

The book calls the gut the first brain and the skull the second, and the spine sits downstream of the first. Several drivers keep that first brain inflamed. Diets heavy in acellular carbohydrates leave the short-chain fatty acid producers underfed, and those compounds are what the gut lining burns. Industrial seed oils feed metaflammation. Night pain that breaks up sleep belongs on the list too. Then the social driver: a system that sends the bowel to one specialist and the spine to another, so the patient ends up as the only person holding the whole file.

The barrier those drivers wear down is the subject of the gut wall, and malabsorption from the same bowel drives the low vitamin D covered in what low vitamin D means.

What should you ask your doctor about Crohn’s and back pain?

If you live with Crohn’s disease or ulcerative colitis and your back hurts, ask whether anyone has looked at your sacroiliac joints specifically. Ask whether an HLA-B27 test or a rheumatology referral makes sense for your pain pattern. Ask what your inflammatory markers have done across years, not just this month. And ask for the metabolic and autonomic picture to be measured, so the terrain is documented instead of assumed. Unmeasured is unmanaged. The full study list sits in the Chapter 11 Deep Dive.

Frequently asked questions

References

• Karreman, M. C., Luime, J. J., Hazes, J. M. W., & Weel, A. E. A. M. (2017). The prevalence and incidence of axial and peripheral spondyloarthritis in inflammatory bowel disease: A systematic review and meta-analysis. Journal of Crohn’s & Colitis, 11(5), 631–642. https://doi.org/10.1093/ecco-jcc/jjw199
• Kilic, Y., Kamal, S., Jaffar, F., Sriranganathan, D., Quraishi, M. N., & Segal, J. P. (2024). Prevalence of extraintestinal manifestations in inflammatory bowel disease: A systematic review and meta-analysis. Inflammatory Bowel Diseases, 30(2), 230-239. https://doi.org/10.1093/ibd/izad061
• Lin, A., Tan, Y., Chen, J., Liu, X., & Wu, J. (2023). Development of ankylosing spondylitis in patients with ulcerative colitis: A systematic meta-analysis. PLoS One, 18(8), e0289021. https://doi.org/10.1371/journal.pone.0289021
• Taurog, J. D., Richardson, J. A., Croft, J. T., Simmons, W. A., Zhou, M., Fernández-Sueiro, J. L., Balish, E., & Hammer, R. E. (1994). The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. The Journal of Experimental Medicine, 180(6), 2359–2364. https://doi.org/10.1084/jem.180.6.2359
• Jensen, T. S., Karppinen, J., Sorensen, J. S., Niinimäki, J., & Leboeuf-Yde, C. (2008). Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain. European Spine Journal, 17(11), 1407–1422. https://doi.org/10.1007/s00586-008-0770-2
• Brinjikji, W., Diehn, F. E., Jarvik, J. G., Carr, C. M., Kallmes, D. F., Murad, M. H., & Luetmer, P. H. (2015). MRI findings of disc degeneration are more prevalent in adults with low back pain than in asymptomatic controls: A systematic review and meta-analysis. AJNR. American Journal of Neuroradiology, 36(12), 2394–2399. https://doi.org/10.3174/ajnr.A4498
• Bråten, L. C. H., Rolfsen, M. P., Espeland, A., Wigemyr, M., Aßmus, J., Froholdt, A., Haugen, A. J., Marchand, G. H., Kristoffersen, P. M., Lutro, O., Randen, S., Wilhelmsen, M., Winsvold, B. S., Kadar, T. I., Holmgard, T. E., Vigeland, M. D., Vetti, N., Nygaard, Ø. P., Lie, B. A., … Zwart, J.-A. (2019). Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial. BMJ, 367, l5654. https://doi.org/10.1136/bmj.l5654
• Cicuttini, F. M., Wluka, A. E., Pan, F., O’Sullivan, R., Leder, K., Cheng, A. C., & Urquhart, D. M. (2026). Efficacy of antibiotics for chronic low back pain with disc herniation: a randomized clinical trial. JAMA Network Open, 9(5), e2612848. https://doi.org/10.1001/jamanetworkopen.2026.12848
• Rajasekaran, S., Vasudevan, G., Easwaran, M., Devi Ps, N., Anand K S, S. V., Murugan, C., Shetty, A. P., Kanna, R. M., & Tangavel, C. (2023). “Are we barking up the wrong tree? Too much emphasis on Cutibacterium acnes and ignoring other pathogens” – a study based on next-generation sequencing of normal and diseased discs. The Spine Journal, 23(10), 1414–1426. https://doi.org/10.1016/j.spinee.2023.06.396

Related reading

• What Does Low Vitamin D Mean? Reading the Number on Your Report
• Leaky Blood-Brain Barrier: The Body Numbers That Predict It Early
• Laboratory Panels

Are Seed Oils Bad for You? What Your Numbers Can Actually Show

Seed oils are neither poison nor simply safe. Their omega-6 fats oxidize easily and supply the raw material for inflammatory signals, so the concern is exposure: how much of your fat comes from these oils, and how often that oil was heated and reused before you ate it.

The fight over seed oils is mostly a fight over measurement: which oil, in what condition, read by which test. Your gut wall and your arteries keep a record that argument rarely checks.

Are seed oils bad for you? The question usually gets asked as if oil in a sealed bottle, oil in a restaurant fryer on its fourth day and a fatty acid in a blood sample were the same thing. They are not, and most of the shouting comes from treating them as one exposure. The gut side of that argument plays out in Your Gut Wall Is What You Fried Last Week, drawn from The Angry Gut by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes. The question here is practical: what can be measured in you, and what a result is allowed to mean.

Are seed oils bad for you? Poison and safe are both wrong

Industrial seed oils are rich in omega-6 fats. Those fats are chemically reactive. They oxidize easily, and they supply the raw material for the signals that switch inflammation on. None of that makes a bottle of oil a toxin, and Dr. Padda does not call it one. His position is about exposure: how much of your fat comes from these oils, how often that oil was heated and reused before you ate it, and whether anything else on your plate balances it.

The studies that reassure people usually count something different. A blood test for a fatty acid reads the intact molecule that survived, typically drawn once, and it cannot tell fresh oil from oil that sat in a fryer all week. Such a study can clear the fatty acid and still say nothing about the degraded oil most people eat. Researchers call that exposure misclassification. It is a reason to ask what any number, in a study or on your report, was really counting.

How do seed oils affect your gut?

Your gut is the first brain, and your skull holds the second. The first brain rebuilds its lining every few days from fatty acids that arrived recently. Membrane fat is not stored fuel; it is the stock from which inflammatory signals are cut, so the fats on hand shape the message sent. A lining built mostly from omega-6 fat is primed to start inflammation, and the same raw material reaches your arteries, where insulin resistance and high triglycerides may already strain the system.

That is metaflammation with a supply chain. Fryer oil in a hospital cafeteria is cheap because the crop behind it is subsidized, and the night-shift worker eating fried food most days did not set that price or choose that oil. Biology decides what the membrane does with the fat. Economics decides which fat arrives.

What a standard visit checks, and what it misses

A visit for loose stools and belly pain usually ends with a scope, a stool sample or a referral. Those tests look for disease in the bowel. None of them asks what the wall is being built from, and none is designed to. A routine physical adds a cholesterol panel, which describes fat-carrying particles in the blood, not the makeup of a gut membrane.

Even research labs struggle here. In ulcerative colitis, the protective mucus of the colon held 745 pmol of its main waterproofing lipid per 100 µg of protein, compared with 2,790 in healthy people. A drug designed to replace that lipid was stopped in phase 3 because it did not help. A survey of 584 lipid species pointed to the reason: the colon mostly makes that lipid itself. A low level in the tissue did not mean the diet was short of it.

The inflammation off switch makes the same point harder. Resolvins are molecules cut from fat that help end inflammation. Read by mass spectrometry, resolvin D1 comes in around 30 pg/ml. Read by the antibody kits much of the human research relied on, it comes in above 2,000 pg/ml, because those kits also pick up neighboring lipids. A confident figure from the wrong method is worse than no figure, because it stops the search.

What can be measured in the same person

Nobody can sample your gut wall at a screening visit, and Measura [Cardiometabolic and Autonomic Health Analysis] does not try. What can be measured is the terrain that the same fat supply feeds: how your body handles fat and sugar, how your arteries behave, and where your weight actually sits.

• Laboratory panels look at blood work such as triglycerides, HDL cholesterol, glucose and insulin, which together describe how your body is handling fat and sugar.
• Arterial stiffness and endothelial function measures how rigid your larger arteries are and how well the lining of your vessels can open when tissue needs more blood.
• Bioimpedance body composition separates fat from lean tissue, because a normal weight can hide a metabolic problem.

None of these reads your omega-6 to omega-3 balance or diagnoses a bowel disease. A blood fatty acid profile is a separate laboratory question for your physician, and gut symptoms still need their own workup. What Measura shows is whether the metabolic and vascular picture around your gut is quiet or already strained, and the findings go to your physician. What a test result can and cannot tell you covers that boundary, and insulin resistance and metabolic health explains why the terrain matters.

Why isn’t a fish oil capsule the answer?

Dr. Padda spent years as a strict vegetarian cooking in the oils the guidelines approved, and he gave patients that same advice. What changed his mind was pathology, not a headline. He is just as blunt about the opposite shortcut. Fish oil changes membrane makeup quickly, but in Crohn’s disease two large trials enrolling 738 patients at 98 centers saw relapse at 31.6% on fish oil versus 35.7% on placebo in the first trial. Pooled across long-term heart trials, marine omega-3 supplements raised atrial fibrillation, with a hazard ratio of 1.49 above 1 g a day. A pill that nudges one number while adding a rhythm risk is not a plan.

What he uses instead is the kitchen: a different cooking oil, far less restaurant frying, and the fish and full-fat dairy a rushed diet dropped. Changing food changes the same membranes, meal after meal, with no drug-sized dose.

What tests should you ask for if you eat a lot of fried food?

• If you eat fried or restaurant food most days, ask whether your blood work includes triglycerides, HDL cholesterol and fasting insulin, not only total cholesterol.
• If you take fish oil above 1 g a day, bring the dose and your reason for taking it to your physician.
• If your metabolic numbers are drifting and your arteries have never been measured, ask whether vascular testing makes sense for you.
• If gut symptoms have lasted for months, ask for a diagnosis before assuming the cause is your diet.

The short version: seed oils are not poison, studies of fresh oil do not settle the question, and your own terrain can be measured. Questions worth asking your doctor helps you prepare, the full study-by-study evidence is on the Chapter 8 book companion page, and the blood supply those membranes depend on is the subject of what endothelial dysfunction means for your arteries.

Frequently asked questions

References

• Braun, A., Treede, I., Gotthardt, D., Tietje, A., Zahn, A., Ruhwald, R., Schoenfeld, U., Welsch, T., Kienle, P., Erben, G., Lehmann, W.-D., Fuellekrug, J., Stremmel, W., & Ehehalt, R. (2009). Alterations of phospholipid concentration and species composition of the intestinal mucus barrier in ulcerative colitis: a clue to pathogenesis. Inflammatory Bowel Diseases, 15(11), 1705–1720. https://doi.org/10.1002/ibd.20993
• Moe, O. K., Gao, Q., Geng, D., Jensen, E., Goll, R., Nestegard, O., Gundersen, M. D., Meyer, R., Florholmen, J., & Hansen, T. (2025). Marked mucosal lipid shifts in treatment refractory inflammatory bowel disease: a lipidomic study. BMC Gastroenterology, 25(1), 389. https://doi.org/10.1186/s12876-025-03944-6
• Schebb, N. H., Kühn, H., Kahnt, A. S., Rund, K. M., O’Donnell, V. B., Flamand, N., Peters-Golden, M., Jakobsson, P.-J., Weylandt, K. H., Rohwer, N., Murphy, R. C., Geisslinger, G., FitzGerald, G. A., Hanson, J., Dahlgren, C., Alnouri, M. W., Offermanns, S., & Steinhilber, D. (2022). Formation, signaling and occurrence of specialized pro-resolving lipid mediators — what is the evidence so far? Frontiers in Pharmacology, 13, 838782. https://doi.org/10.3389/fphar.2022.838782
• Feagan, B. G., Sandborn, W. J., Mittmann, U., Bar-Meir, S., D’Haens, G., Bradette, M., Cohen, A., Dallaire, C., Ponich, T. P., McDonald, J. W. D., Hébuterne, X., Paré, P., Klvana, P., Niv, Y., Ardizzone, S., Alexeeva, O., Rostom, A., Kiudelis, G., Spleiss, J., … Greenberg, G. R. (2008). Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC randomized controlled trials. JAMA, 299(14), 1690–1697. https://doi.org/10.1001/jama.299.14.1690
• Gencer, B., Djousse, L., Al-Ramady, O. T., Cook, N. R., Manson, J. E., & Albert, C. M. (2021). Effect of long-term marine ɷ-3 fatty acids supplementation on the risk of atrial fibrillation in randomized controlled trials of cardiovascular outcomes: A systematic review and meta-analysis. Circulation, 144(25), 1981–1990. https://doi.org/10.1161/CIRCULATIONAHA.121.055654
• Imamura, F., Fretts, A., Marklund, M., Ardisson Korat, A. V., Yang, W.-S., Lankinen, M., Qureshi, W., Helmer, C., Chen, T.-A., Wong, K., Bassett, J. K., Murphy, R., Tintle, N., Yu, C. I., Brouwer, I. A., Chien, K.-L., Frazier-Wood, A. C., Del Gobbo, L. C., Djoussé, L., … Mozaffarian, D. (2018). Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. PLoS Medicine, 15(10), e1002670. https://doi.org/10.1371/journal.pmed.1002670
• Venn-Watson, S. (2024). The cellular stability hypothesis: Evidence of ferroptosis and accelerated aging-associated diseases as newly identified nutritional pentadecanoic acid (C15:0) deficiency syndrome. Metabolites, 14(7), 355. https://doi.org/10.3390/metabo14070355

Related reading

• EDS and POTS: Measuring What a Normal Workup Misses
• What Is Endothelial Dysfunction? The Warning Your Arteries Send
• Laboratory Panels

What Does Echogenic Liver Mean? Reading the Numbers Behind the Scan

Echogenic liver means the ultrasound shows a liver consistent with fatty liver, hepatic steatosis. Because the scan detects fat only once more than 30% of liver cells are loaded, the finding usually means substantial fat is already there, even when liver enzymes read normal.

An ultrasound report calls your liver echogenic, and your enzymes are called normal. Both can be true while a fatty liver sits upstream of your heart and your metabolism.

What does echogenic liver mean? On an ultrasound report, a liver described as diffusely echogenic is the radiologist’s way of saying it looks consistent with hepatic steatosis, a fatty liver. The video above, The Alcohol You Never Drank, is Chapter 5 of The Angry Gut by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes. It opens with the question almost everyone asks after that report: how does fat get into a liver when the person does not drink?

Two things tend to arrive with the scan. The liver enzymes are called fine, and the advice is to lose weight. Both deserve a closer look, because neither tells you what put the fat there or what it is doing to the rest of your body.

What does echogenic liver mean on the scan?

Ultrasound is a blunt instrument for liver fat. British guidance on abnormal liver tests notes that the scan only picks up fat once more than 30% of liver cells are loaded. So an echogenic report usually means a substantial amount of fat is already there. The reverse matters too: a scan read as normal does not rule out milder fatty liver, especially when blood markers and metabolic risk factors point the other way.

Liver imaging is done by the physician or imaging service that ordered it. What a picture of the liver cannot tell you is how the metabolism around that liver is behaving, and that part can be measured.

How does fat get into the liver if you do not drink?

Everything your bowel absorbs travels to the liver first, through the portal vein, before your heart sees any of it. The gut is the first brain, the skull holds the second, and when the gut is inflamed the liver hears about it first. Surgeons have sampled that vein. In patients having elective abdominal operations, portal blood carried endotoxin, a bacterial fragment the immune system treats as an alarm, in 97% of cases, while arm blood tested positive in just 4 of 34 people.

Researchers later sampled the same vein for alcohol. In people having bariatric surgery, portal ethanol ran a median 187 times higher than fasting arm blood. Levels tracked the stage of disease: 21.0 mM in steatohepatitis, the inflamed stage, against 8.0 mM in simple fatty liver and 2.1 mM without liver fat. Gut organisms ferment sugar into alcohol, and a working liver clears it so quickly that an ordinary blood test never catches it.

There is a fair counterargument. In children with early fatty liver, and in mice, the bigger difference was clearance rather than production: an insulin-resistant liver broke alcohol down more slowly. Either way the road runs through insulin, and nobody has yet run the clinical study that would prove cause and effect. The mechanism remains the best explanation for the patient that clean trials leave out.

The supply side is economic. Subsidized crops make sweetener abundant, so food makers put it almost everywhere, and a gut that meets sugar at every meal never runs short of fermentation fuel.

Why can liver enzymes be normal with an echogenic liver?

The liver works as a filter around the clock, and blood drawn from the arm samples what that filter has already cleaned. That is one reason enzymes can look unremarkable beside an echogenic scan.

One number on a standard panel reads the strain better than most. GGT, gamma-glutamyl transferase, sits on the cell surface and helps the cell rebuild its antioxidant supply, so a cell under oxidative stress makes more of it. In a Korean cohort of 9,687,066 adults followed a median 8.3 years, the highest third of GGT carried a hazard ratio of 1.33 for death from any cause after adjustment for alcohol, body mass index and other liver enzymes. For women, that highest third started at 21 IU/L, a value every laboratory prints as normal.

GGT has honest limits. Obesity raises it more often than alcohol does, and people with genetically higher GGT were not more likely to develop diabetes or heart disease, so it reports strain rather than causing it. Its value is the trend: a GGT drifting upward inside the reference range over years says the system is working harder.

Dr. Padda ended visits for years with the advice to lose some weight and believed he had done something useful. For someone who has already lost and regained the weight several times, one more instruction explains nothing about why fat went to the liver.

Can you have a fatty liver at a normal weight?

The calorie argument is real. In the largest randomized trial of a synbiotic for fatty liver, weight loss was the only factor that moved liver fat. But arithmetic cannot explain why two people with the same surplus end up with different livers, or why a South Asian man with a normal body mass index and thin limbs can carry a liver packed with fat while being told his weight is fine.

What the liver responds to is delivery. Resistant starch, given for four months in a randomized trial, cut liver fat by 9.08%, and by 5.89% once weight loss was accounted for. In a small six-week study, inulin, a fermentable fiber, pushed liver fat up from 20.9% to 26.8%, most likely because gut bacteria turned it into acetate, a raw material the liver builds fat from. Two ways of feeding the gut, and the liver went in opposite directions.

Weight is the wrong yardstick for a disease that follows delivery and insulin. That gap is exactly what body composition and metabolic laboratory work are built to fill.

What Measura can measure around a fatty liver

Measura [Cardiometabolic and Autonomic Health Analysis] does not image the liver; ultrasound and other liver imaging are done elsewhere. It measures the terrain a fatty liver sits in, and every finding goes to your physician:

• Laboratory panels ordered with your physician can place GGT and other liver enzymes beside glucose, insulin and lipids, so a drift is read in context rather than one value at a time.
• Bioimpedance body composition separates fat from muscle, which is how thin outside and fat inside becomes visible when BMI says normal. More on that in body composition, not BMI.
• Arterial stiffness and endothelial function testing looks at the blood vessels. Across 23 studies and more than a million people, higher GGT predicted cardiovascular death, and the arteries are where that risk plays out, as finding cardiovascular risk early explains.

Measura does not diagnose fatty liver or treat it.

What to bring to your next appointment

• Every GGT result you can find, from as many years back as your records go. One value is a snapshot; several make a trend.
• How much fat would my liver need before the ultrasound showed anything?
• Has my insulin been measured, not only my glucose?
• Can we look at my body composition rather than my weight alone?
• Given my liver and my GGT, should my blood vessels be checked?

More prompts are on questions worth asking your doctor. The wall that decides how much reaches the portal vein is covered in the previous post on testing for leaky gut, and what happens when the bowel cannot absorb what it is given comes next in the following post. Every study above, with what it cannot show, is in the Chapter 5 book companion. Unmeasured is unmanaged, and a normal enzyme beside an echogenic scan is a question, not an answer. Once fat is on the scan, the next question is scarring, and a routine blood panel can be turned into a fatty liver fibrosis score.

Frequently asked questions

References

• Newsome, P. N., Cramb, R., Davison, S. M., Dillon, J. F., Foulerton, M., Godfrey, E. M., Hall, R., Harrower, U., Hudson, M., Langford, A., Mackie, A., Mitchell-Thain, R., Sennett, K., Sheron, N. C., Verne, J., Walmsley, M., & Yeoman, A. (2018). Guidelines on the management of abnormal liver blood tests. Gut, 67(1), 6-19. https://doi.org/10.1136/gutjnl-2017-314924
• Jacob, A. I., Goldberg, P. K., Bloom, N., Degenshein, G. A., & Kozinn, P. J. (1977). Endotoxin and bacteria in portal blood. Gastroenterology, 72(6), 1268–1270. https://pubmed.ncbi.nlm.nih.gov/858472/
• Meijnikman, A. S., Davids, M., Herrema, H., Aydin, O., Tremaroli, V., Rios-Morales, M., Levels, H., Bruin, S., de Brauw, M., Verheij, J., Kemper, M., Holleboom, A. G., Tushuizen, M. E., Schwartz, T. W., Nielsen, J., Brandjes, D., Dallinga-Thie, G. M., Havik, S. R., Ackermans, M. T., … Nieuwdorp, M. (2022). Microbiome-derived ethanol in nonalcoholic fatty liver disease. Nature Medicine, 28(10), 2100–2106. https://doi.org/10.1038/s41591-022-02016-6
• Engstler, A. J., Aumiller, T., Degen, C., Durr, M., Weiss, E., Maier, I. B., Schattenberg, J. M., Jin, C. J., Sellmann, C., & Bergheim, I. (2016). Insulin resistance alters hepatic ethanol metabolism: Studies in mice and children with non-alcoholic fatty liver disease. Gut, 65(9), 1564–1571. https://doi.org/10.1136/gutjnl-2014-308379
• Cho, E. J., Jeong, S.-M., Chung, G. E., Yoo, J.-J., Cho, Y., Lee, K.-N., Shin, D. W., Kim, Y. J., Yoon, J.-H., Han, K., & Yu, S. J. (2023). Gamma-glutamyl transferase and risk of all-cause and disease-specific mortality: a nationwide cohort study. Scientific Reports, 13(1), 1751. https://doi.org/10.1038/s41598-022-25970-0
• Liu, J., Au Yeung, S. L., Lin, S. L., Leung, G. M., & Schooling, C. M. (2016). Liver enzymes and risk of ischemic heart disease and type 2 diabetes mellitus: A Mendelian randomization study. Scientific Reports, 6, 38813. https://doi.org/10.1038/srep38813
• Rahmani, J., Miri, A., Namjoo, I., Zamaninour, N., Maljaei, M. B., Zhou, J. B., Shokouhi Nasab Kermani, R., Kord Varkaneh, H., Fatahi, S., & Zhang, Y. (2019). Elevated liver enzymes and cardiovascular mortality: a systematic review and dose-response meta-analysis of more than one million participants. European Journal of Gastroenterology & Hepatology, 31(5), 555–562. https://doi.org/10.1097/MEG.0000000000001353
• Scorletti, E., Afolabi, P. R., Miles, E. A., Smith, D. E., Almehmadi, A., Alshathry, A., Childs, C. E., Del Fabbro, S., Bilson, J., Moyses, H. E., Clough, G. F., Sethi, J. K., Patel, J., Wright, M., Breen, D. J., Peebles, C., Darekar, A., Aspinall, R., Fowell, A. J., … Byrne, C. D. (2020). Synbiotics alter fecal microbiomes, but not liver fat or fibrosis, in a randomized trial of patients with nonalcoholic fatty liver disease. Gastroenterology, 158(6), 1597–1610.e7. https://doi.org/10.1053/j.gastro.2020.01.031
• Ni, Y., Qian, L., Siliceo, S. L., Long, X., Nychas, E., Liu, Y., Ismaiah, M. J., Leung, H., Zhang, L., Gao, Q., Wu, Q., Zhang, Y., Jia, X., Liu, S., Yuan, R., Zhou, L., Wang, X., Li, Q., Zhao, Y., … Jia, W. (2023). Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations. Cell Metabolism, 35(9), 1530-1547.e8. https://doi.org/10.1016/j.cmet.2023.08.002
• Chambers, E. S., Byrne, C. S., Rugyendo, A., Morrison, D. J., Preston, T., Tedford, C., Bell, J. D., Thomas, L., Akbar, A. N., Riddell, N. E., Sharma, R., Thursz, M. R., Manousou, P., & Frost, G. (2019). The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. Diabetes, Obesity & Metabolism, 21(2), 372–376. https://doi.org/10.1111/dom.13500

Related reading

• How to Test for Leaky Gut, and Why Zonulin Is the Wrong Test
• Atrophic Gastritis: When Your Stomach Stops Absorbing B12
• Laboratory Panels

Can Inflammation Cause Anxiety? What Blood Work and Testing Show

Inflammation can contribute to anxiety in a subset of people, not in everyone. That subset only shows up when someone measures, starting with inflammatory blood markers such as C-reactive protein chosen with your physician.

Anxiety is usually treated as a problem inside the skull. A growing set of experiments says some of it is lit lower down, and part of that fire leaves marks in ordinary blood work.

Can inflammation cause anxiety? In a subset of people the evidence says it can contribute, and that subset only shows up when someone measures. Dr. Padda’s video Your Anxiety Is a Fire in Your Gut argues that the gut, the first brain, can inflame the second brain in your skull. Measura [Cardiometabolic and Autonomic Health Analysis] asks the practical follow-up: what in your own numbers would show whether that argument applies to you?

Can inflammation change your mood?

The strongest human evidence is experimental. Healthy volunteers given a small dose of bacterial endotoxin, a fragment of the outer coat of gut bacteria, develop lower mood under placebo-controlled conditions. In a trial of one hundred and fifteen healthy adults randomized to endotoxin or saline, the people whose mood fell furthest already carried more perceived stress, more sensitivity to feeling socially cut off and more baseline anxiety. Their inflammatory chemicals did not rise any higher than everyone else’s. What differed was the size of the response.

Hepatitis C clinics watched the same thing for two decades. Interferon, an inflammatory messenger given as treatment, brought on major depression in roughly one patient in four by 24 weeks, more often in people with a prior depressive episode or higher baseline interleukin-6.

Can the gut trigger anxiety?

Anxiety-like behavior has been produced from the gut lining itself. In mice, switching on enterochromaffin cells, the serotonin-releasing cells of the intestinal lining, made the gut hypersensitive and triggered anxiety-like behavior that settled once serotonin signaling was blocked. No serotonin had to reach the brain, and it could not have: although roughly 90 to 95 percent of all serotonin in the body is made in the gut, that supply does not cross the blood-brain barrier. The message travels on nerves, and through inflammation, which steers tryptophan away from the brain’s own serotonin supply.

Dr. Padda admits he used to give patients the simpler story, that a gut making serotonin must be running their mood. The manufacturing half held up. The delivery half did not, and correcting it is what points toward inflammation as the link that can actually be measured.

The wall of the first brain also answers to how people live. In healthy married couples, more hostile arguments went with more of a blood marker for bacterial fragments crossing the gut wall, and that marker tracked whole-body inflammation: 79 percent of people in its highest group had an average daytime CRP above 3, against 21 percent in its lowest. A food supply built on flour and sugar, stripped of fermentable fiber, adds fuel from the plate. Across The Angry Gut, that combined terrain goes by one name, metaflammation.

Does inflammation cause anxiety in everyone?

Inflammation does not explain everyone. Across 30 studies of people with depression, 27 percent had a C-reactive protein, or CRP, above 3 mg/L, the usual line for low-grade inflammation; at a cutoff of 1 mg/L the share was 58 percent. Those figures come from depression research rather than anxiety research, but the shape is the point: an inflamed minority exists, and nobody can see it without a blood draw. In one treatment trial, an antibody that blocks an inflammatory signal helped depressed patients only when their CRP sat above 5 mg/L.

What does a routine anxiety visit miss?

Anxiety is usually assessed with a conversation and a questionnaire, while digestive symptoms are sent to a different clinic. CRP and fasting insulin may never be drawn, and when they are, no one may connect them to mood. A stool microbiome report does not close that gap. Large microbiome studies of depression have replicated poorly, and the same bacterial shifts appear across depression, bipolar disorder, schizophrenia and anxiety alike. Measura does not offer stool, breath or microbiome tests.

Which tests show whether inflammation is behind anxiety?

• Laboratory panels report metabolic and inflammatory blood markers. Whether CRP and fasting insulin are included is decided with your physician, and one high CRP calls for a repeat, since infection, injury or a hard workout can also push it up.
• Bioimpedance body composition separates fat from muscle, the tissue picture that tends to accompany high insulin and a widening waist.
• Heart rate variability records beat-to-beat variation in your heart rate, a measure of how the autonomic nervous system is regulating at rest. It describes regulation; it does not diagnose anxiety.

None of these tests diagnoses an anxiety disorder or replaces the clinician treating your mood. Every result goes to your physician, who decides what it means. What the numbers add is evidence about whether an inflamed, metabolically strained body sits underneath the symptom. For how results are read, see understanding your results.

Questions to bring, and what not to change

• Has my CRP ever been measured, and if it was above 3 mg/L, was it repeated and explained?
• What is my fasting insulin as a number, not only my glucose?
• Can the clinician treating my gut and the one treating my mood see each other’s notes?
• How many antibiotic courses have I had in recent years, and is that written into my history?

Nothing here is a reason to stop or adjust a psychiatric medication. That decision stays between you and the physician who prescribed it. Food still belongs in the conversation: in the SMILES trial of adults with major depression, remission rates were 32.3 percent with dietary support and 8.0 percent with social support. That sits alongside the prescription, not in place of it.

Every study behind these figures, including the genetic work that argues against this model, is laid out in the Chapter 1 Deep Dive for The Angry Gut by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes. If you missed the start of the series, read what a vagus nerve test can and cannot show, then continue to what else is in the pill you already take.

Frequently asked questions

References

• Irwin, M. R., Cole, S., Olmstead, R., Breen, E. C., Cho, J. J., Moieni, M., & Eisenberger, N. I. (2019). Moderators for depressed mood and systemic and transcriptional inflammatory responses: A randomized controlled trial of endotoxin. Neuropsychopharmacology, 44(3), 635–641. https://doi.org/10.1038/s41386-018-0259-6
• Udina, M., Castellví, P., Moreno-España, J., Navinés, R., Valdés, M., Forns, X., Langohr, K., Solà, R., Vieta, E., & Martín-Santos, R. (2012). Interferon-induced depression in chronic hepatitis C: A systematic review and meta-analysis. The Journal of Clinical Psychiatry, 73(8), 1128–1138. https://doi.org/10.4088/JCP.12r07694
• Bayrer, J. R., Castro, J., Venkataraman, A., Touhara, K. K., Rossen, N. D., Morrie, R. D., Maddern, J., Hendry, A., Braverman, K. N., Garcia-Caraballo, S., Schober, G., Brizuela, M., Castro Navarro, F. M., Bueno-Silva, C., Ingraham, H. A., Brierley, S. M., & Julius, D. (2023). Gut enterochromaffin cells drive visceral pain and anxiety. Nature, 616(7955), 137-142. https://doi.org/10.1038/s41586-023-05829-8
• Chen, Y., Xu, J., & Chen, Y. (2021). Regulation of neurotransmitters by the gut microbiota and effects on cognition in neurological disorders. Nutrients, 13(6), 2099. https://doi.org/10.3390/nu13062099
• Kiecolt-Glaser, J. K., Wilson, S. J., Bailey, M. L., Andridge, R., Peng, J., Jaremka, L. M., Fagundes, C. P., Malarkey, W. B., Laskowski, B., & Belury, M. A. (2018). Marital distress, depression, and a leaky gut: Translocation of bacterial endotoxin as a pathway to inflammation. Psychoneuroendocrinology, 98, 52–60. https://doi.org/10.1016/j.psyneuen.2018.08.007
• Osimo, E. F., Baxter, L. J., Lewis, G., Jones, P. B., & Khandaker, G. M. (2019). Prevalence of low-grade inflammation in depression: A systematic review and meta-analysis of CRP levels. Psychological Medicine, 49(12), 1958–1970. https://doi.org/10.1017/S0033291719001454
• Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., Haroon, E., & Miller, A. H. (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: The role of baseline inflammatory biomarkers. JAMA Psychiatry, 70(1), 31–41. https://doi.org/10.1001/2013.jamapsychiatry.4
• Nikolova, V. L., Smith, M. R. B., Hall, L. J., Cleare, A. J., Stone, J. M., & Young, A. H. (2021). Perturbations in gut microbiota composition in psychiatric disorders: A review and meta-analysis. JAMA Psychiatry, 78(12), 1343–1354. https://doi.org/10.1001/jamapsychiatry.2021.2573
• Scheffler, L., Crane, A., Heyne, H., Tönjes, A., Schleinitz, D., Ihling, C. H., Stumvoll, M., Freire, R., Fiorentino, M., Fasano, A., Kovacs, P., & Heiker, J. T. (2018). Widely used commercial ELISA does not detect precursor of haptoglobin2, but recognizes properdin as a potential second member of the zonulin family. Frontiers in Endocrinology, 9, 22. https://doi.org/10.3389/fendo.2018.00022
• Jacka, F. N., O’Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., Castle, D., Dash, S., Mihalopoulos, C., Chatterton, M. L., Brazionis, L., Dean, O. M., Hodge, A. M., & Berk, M. (2017). A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Medicine, 15(1), 23. https://doi.org/10.1186/s12916-017-0791-y

Related reading

• Is There a Vagus Nerve Test? What Can Actually Be Measured
• Polypharmacy in the Elderly: What Nine Bottles Hide From Your Numbers
• Laboratory Panels

How to Lower Insulin Resistance: What Moves It, and How to Tell

Insulin resistance is lowered through food, sleep, movement and weight loss, with the weight goal written as a percentage; 5 percent is the national prevention program’s target. You know it is working by rechecking fasting insulin beside fasting glucose, A1c, kidney function and body composition against your own baseline.

Long-standing pain usually comes with adjectives: mild, degenerative, chronic. Adjectives cannot be rechecked in a few months. Insulin, A1c and body composition can, which is how you find out whether anything you changed is working.

How to lower insulin resistance is a question most people ask only after a diagnosis, and it is hard to answer without a starting number. When the body resists insulin, it tends to make more of it, so insulin can climb while glucose still looks acceptable. For someone who has lived with pain for years, that quiet climb is one of the few parts of the story that can be measured, changed and measured again; what a fasting insulin test shows is covered separately. The chapter video, Empowered Individuals Change Their Communities, closes The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, with a school bus driver whose A1c went from 8.1 to 5.8 over two years. Her story is one person’s course, not a trial outcome, and individual results vary.

The odds nobody prints, and the part that moves

In a national sample of American adults with chronic pain in 2019, 61.4 percent still had it a year later and 10.4 percent reported no pain. In Norway, recovery among people with moderate or severe chronic pain was 8 percent within a year, and the researchers found the outlook worsens once pain has lasted several years. Across eight survey waves in another Norwegian group, only 11 percent followed a path of steady improvement, while 31 percent moved back and forth across the line between chronic pain and none.

Those are averages for people handed nothing but time. Belief is part of the math: in 406 people whose back pain had just become chronic, every point of higher expected risk that the pain would last slowed recovery, a hazard ratio of 0.91. The body is the other part. Blood sugar, insulin, body fat, kidney function, sleep and movement are not fixed traits, and each one has a number attached.

Why can a normal blood sugar test miss insulin resistance?

Fasting glucose or A1c is where most screening stops. Those numbers matter, and research defines remission of type 2 diabetes by an A1c under 6.5 percent. But glucose tends to be the late signal. In one remote-coaching program built on carbohydrate restriction, a measure of insulin resistance called HOMA-IR fell 55 percent in a year, a shift a glucose value alone would not reveal. That study was funded by the company running the program, which is worth knowing when weighing it.

Kidney function belongs in the same conversation. When 1,779 people from the national diabetes prevention trial were reassessed about 21 years after they entered it, painful nerve symptoms tracked higher body weight and lower kidney filtration and were not associated with blood sugar. For someone with burning or aching feet, that points at weight and the kidneys as much as at the glucose meter.

The scale can mislead in the other direction too. In 20 people with type 2 diabetes and a body mass index under 27, losing 6.5 percent of body weight put 70 percent into remission as liver fat returned to normal, and about one in six people is at that kind of weight when diagnosed. A normal BMI does not guarantee normal metabolism, which is why fat mass is worth measuring directly.

Which numbers should you track to lower insulin resistance?

• Fasting insulin, read beside fasting glucose, to look for insulin resistance before glucose rises.
• A1c, the average of blood sugar over roughly three months, with a target written down.
• Kidney function, especially when nerve pain is part of the picture.
• A weight goal written as a percentage. In knee arthritis trials, pain relief was expected at about 7 percent of body weight lost, and 5 percent is the goal the national prevention program uses.
• Body composition, so fat and lean mass are measured instead of guessed from BMI.
• Your own expectation of recovery, recorded where you and your physician can both see it.

More on the metabolic side is at insulin resistance and metabolic health, and the evidence behind each marker is in the book companion for chapter 22.

What Measura measures

Measura [Cardiometabolic and Autonomic Health Analysis] is a testing service. It measures and reports to your physician; it does not diagnose disease on its own, prescribe or treat. Two of its measurements match the list above. Laboratory panels are where blood markers such as glucose, A1c and kidney function are drawn; ask your physician whether fasting insulin is included in the panel being ordered. Bioimpedance body composition estimates fat mass and lean mass with a small, painless electrical signal, showing what a scale reading and a BMI cannot. Whether testing makes sense for you is covered in who should be tested.

How do you know insulin resistance is getting better?

Teaching fades. Across diabetes education programs, A1c improved by about 0.57 on average, ten or more contact hours marked the point where programs reliably worked, and the early gain drifted back toward baseline by 52 weeks no matter how intense the program had been. Feedback slows the fade. Among 9,768 smart-scale owners, a break of 30 days or more without weighing was followed by 1.37 kilograms of gain in people with obesity. A number that gets checked again is a number that tends to hold.

The same logic applies to blood work and body composition. A baseline shows where you are. A repeat later shows whether changes in food, sleep and movement are working, before memory and motivation decide the question for you. What insulin resistance looks like before diabetes describes the pattern those repeats can catch.

One kitchen changes more than one person

A change made by one person rarely stays with that person. In a large diabetes lifestyle trial, spouses who were never enrolled lost 2.2 kilograms against 0.2 among spouses in the comparison group, and about a quarter of those spouses, against 9 percent in the comparison group, dropped 5 percent or more of their weight, with fewer high-fat foods kept at home. Pain moves through families as well: a mother’s chronic pain was tied to 1.59 times the odds of pain complaints in her children. The household is part of the terrain, which makes it worth bringing someone from home to the appointment.

The health system has not solved this for you. The best-proven prevention program in the country reached 455,954 people in eight years against more than 88 million adults at risk, and the people who needed it most lost the least weight. A person holding their own numbers does not have to wait for that gap to close. And if hopelessness about your condition has set in, say it out loud: among 720 hospital inpatients, it carried 5.69 times the odds of a positive suicide risk screen, more than chronic pain itself, and it is a treatable medical finding. How mood and metabolism connect is covered in inflammation and depression, and physicians can read the referral version.

Frequently asked questions

References

• Nahin, R. L., Feinberg, T., Kapos, F. P., & Terman, G. W. (2023). Estimated Rates of Incident and Persistent Chronic Pain Among US Adults, 2019-2020. JAMA Network Open, 6(5), e2313563. https://doi.org/10.1001/jamanetworkopen.2023.13563
• Landmark, T., Dale, O., Romundstad, P., Woodhouse, A., Kaasa, S., & Borchgrevink, P. C. (2018). Development and course of chronic pain over 4 years in the general population: The HUNT pain study. European Journal of Pain, 22(9), 1606–1616. https://doi.org/10.1002/ejp.1243
• Costa, L. da C. M., Maher, C. G., McAuley, J. H., Hancock, M. J., Herbert, R. D., Refshauge, K. M., & Henschke, N. (2009). Prognosis for patients with chronic low back pain: inception cohort study. BMJ, 339, b3829. https://doi.org/10.1136/bmj.b3829
• Taylor, R., Barnes, A. C., Hollingsworth, K. G., Irvine, K. M., Solovyova, A. S., Clark, L., Kelly, T., Martin-Ruiz, C., Romeres, D., Koulman, A., Meek, C. M., Jenkins, B., Cobelli, C., & Holman, R. R. (2023). Aetiology of Type 2 diabetes in people with a ‘normal’ body mass index: testing the personal fat threshold hypothesis. Clinical Science, 137(16), 1333–1346. https://doi.org/10.1042/CS20230586
• Herman, W. H., Ciarleglio, A., Callaghan, B. C., Edelstein, S. L., Goldberg, R., White, N. H., & Albers, J. W. (2025). Nonglycemic and Glycemic Risk Factors for Painful Neuropathic Symptoms and for Distal Symmetrical Polyneuropathy (DSPN) in the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study. Diabetes Care, 48(10), 1676–1684. https://doi.org/10.2337/dc25-0596
• Shahid, A., Thirumaran, A. J., Christensen, R., Venkatesha, V., Henriksen, M., Bowden, J. L., & Hunter, D. J. (2024). Comparison of weight loss interventions in overweight and obese adults with knee osteoarthritis: A systematic review and network meta-analysis of randomized trials. Osteoarthritis and Cartilage, 33(4), 518–529. https://doi.org/10.1016/j.joca.2024.08.012
• Dughmosh, R., Hamdan, A., Moghassabi, W., Al-Kahlout, L., Syed, A., Alwisi, N., Al-Sharif, N., Othman, M., & Doi, S. A. R. (2026). Glycemic trajectory after face-to-face diabetes self-management education: a dose-response meta-analysis. Diabetes Research and Clinical Practice, 238, 113375. https://doi.org/10.1016/j.diabres.2026.113375
• Vuorinen, A.-L., Helander, E., Pietilä, J., & Korhonen, I. (2021). Frequency of Self-Weighing and Weight Change: Cohort Study With 10,000 Smart Scale Users. Journal of Medical Internet Research, 23(6), e25529. https://doi.org/10.2196/25529
• Gorin, A. A., Wing, R. R., Fava, J. L., Jakicic, J. M., Jeffery, R., West, D. S., Brelje, K., & Dilillo, V. G. (2008). Weight loss treatment influences untreated spouses and the home environment: evidence of a ripple effect. Int J Obes (Lond), 32(11), 1678–84. https://doi.org/10.1038/ijo.2008.150
• Hallberg, S. J., McKenzie, A. L., Williams, P. T., Bhanpuri, N. H., Peters, A. L., Campbell, W. W., Hazbun, T. L., Volk, B. M., McCarter, J. P., Phinney, S. D., & Volek, J. S. (2018). Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study. Diabetes Therapy, 9(2), 583–612. https://doi.org/10.1007/s13300-018-0373-9

Related reading

• Chronic Pain and Depression: What Your Blood Work Can Show
• Laboratory Panels

Chronic Pain and Depression: What Your Blood Work Can Show

Blood work can show the inflammation and insulin resistance that tie chronic pain and depression together: C-reactive protein, fasting glucose and A1c, and the triglyceride and HDL pair. It cannot diagnose depression, but it flags the people in whom inflammation, blood sugar and mood are moving together.

Being told your pain is probably stress sounds like a verdict on your mind. For a sizable share of people with low mood, it is also a finding in the blood that nobody drew.

Chronic pain and depression are usually handled in different offices, by different specialists, on different forms, even though inflammation and blood sugar tie them together. That split has a price: the mood gets a questionnaire, the pain gets a scan, and the blood markers that connect the two often never get drawn. That gap is the argument of You Cannot Separate the Mind from the Metabolism, the video for chapter 21 of The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD. The focus here is a narrower question: what would a measurement show in a real person, and what does the usual workup leave out?

How common is depression in people with chronic pain?

In pooled studies of adults with chronic pain, 36.7 percent carried a diagnosis of major depression, ranging from 29.1 percent in osteoarthritis to 54.0 percent in fibromyalgia. Questionnaires find more: across 376 studies, 39.3 percent had clinically significant depressive symptoms. A screen is not a diagnosis, and neither figure means the pain is psychological. What they mean is that low mood shows up beside pain so often that overlooking it is an error of its own.

The trouble starts when a physician notices the mood and stops. Patients told their pain is mostly stress often hear that it is not real.

How does inflammation in the blood relate to depression?

Depression is not only a pattern of thought. In a measurable subgroup it is an inflammatory state. Across 24 studies, people with major depression carried higher levels of two inflammatory messengers, tumor necrosis factor and interleukin-6. In pooled data on C-reactive protein, a routine marker of inflammation, 27 percent of depressed patients sat above 3 milligrams per liter and 58 percent above 1, at 1.46 times the odds of low-grade inflammation seen in matched controls.

The other side of that finding matters just as much. Roughly three quarters of depressed patients stay below the higher line. A C-reactive protein result cannot tell anyone whether they are depressed, and a normal value does not rule depression out. What it can do is flag the people in whom inflammation and mood are moving together, which changes what is worth working on.

Is insulin resistance linked to depression?

Insulin resistance, the state in which the body needs more and more insulin to handle the same meal, runs alongside depression in both directions. People who started out depressed faced 1.60 times the risk of developing type 2 diabetes, and people with diabetes faced 1.15 times the risk of developing depression. In a Dutch cohort of 601 adults with no history of depression, followed for nine years, a higher triglyceride-to-HDL ratio predicted a first major depression at a hazard of 1.89, higher fasting glucose at 1.37, and slipping into prediabetes during the first two years at 2.66.

Weight shows the same two-way pattern, with odds ratios of 1.55 from obesity toward depression and 1.58 from depression toward obesity. Treatment sits inside the loop as well. Among 294,719 British adults, antidepressant use was linked to a higher rate of gaining 5 percent of body weight, 11.2 against 8.1 per 100 person-years. That is not a reason to refuse or stop a medication; that decision belongs to you and your physician. It is a reason to have weight and glucose recorded before treatment begins, so any change is seen rather than guessed.

How does metabolic health affect chronic pain?

In a United States midlife cohort of 781 people, about a quarter showed a metabolic pattern: higher fasting glucose, A1c, triglycerides and waist size, with lower HDL. Seven years later, people in that group were about twice as likely, at 2.00 and 2.03 times, to have pain disrupting daily life or pain in three or more places. The pattern did not predict whether pain existed at all. It predicted how far pain spread and how much of life it took over.

Procedures feel the same terrain. Across 346 patients treated in seven hospitals with injections or radiofrequency procedures, each point of depression score lowered the odds of success, and obesity shrank the relief. An injection can still be the right bridge. The body it lands in decides how far that bridge reaches.

The social layer feeds every part of this. Older adults who felt lonely were more likely to develop chronic pain over the next seven years, an odds ratio of 1.61, and in chronically lonely people 209 genes in white blood cells ran differently, tilted toward inflammation. An empty house belongs in the history next to the lab results.

What blood tests does a typical pain visit miss?

A typical pain visit records a pain score, reviews imaging and may include a mood questionnaire. Many never add the pieces that sit between mood and pain: C-reactive protein, fasting glucose and A1c, the triglyceride and HDL pair, and a measurement of how much of the body is fat. Without them, a person with a rising A1c and a moderate mood score gets two separate conversations instead of one plan.

Measura [Cardiometabolic and Autonomic Health Analysis] is a testing service. It measures; it does not diagnose depression or any other disease on its own, does not treat, and sends results to your physician. Three of its measurements fit the terrain described above:

• Laboratory panels, the route for metabolic and inflammatory blood markers, drawn and trended over time.
• Bioimpedance body composition, which separates fat mass from lean mass so a normal weight does not hide a metabolic problem.
• Heart rate variability, which reflects how the autonomic nervous system, the automatic side of the stress response, balances activation and recovery.

None of these replaces a depression screen done by a clinician. Sleep, which drives much of the loop, is assessed separately and is not a Measura test.

What to ask for, and what numbers can and cannot do

One honest limit belongs on the page. In 665 people with chronic pain in several body regions followed for six years, baseline stress-system, immune and autonomic measures did not predict who improved. The terrain forecasts who gets sick better than it forecasts who gets well. Measure to change something, then measure again.

Useful questions for your next appointment: What is my C-reactive protein? What are my fasting glucose, A1c and triglyceride-to-HDL ratio? If a medication is starting, when will weight and glucose be rechecked? Is isolation in my life being treated as a finding? Plans that reached more than one layer did better: when primary care patients with depression and musculoskeletal pain received combined antidepressant care and pain self-management, 26.0 percent improved in both, against 7.9 percent with usual care. A fuller list is at questions worth asking your doctor, the study-by-study evidence is in the book companion for chapter 21, and what happens when a plan goes home is covered in how to lower insulin resistance and track it. Physicians can read the screening version.

Frequently asked questions

References

• Aaron, R. V., Ravyts, S. G., Carnahan, N. D., Bhattiprolu, K., Harte, N., McCaulley, C. C., Vitalicia, L., Rogers, A. B., Wegener, S. T., & Dudeney, J. (2025). Prevalence of Depression and Anxiety Among Adults With Chronic Pain: A Systematic Review and Meta-Analysis. JAMA Network Open, 8(3), e250268. https://doi.org/10.1001/jamanetworkopen.2025.0268
• Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010). A meta-analysis of cytokines in major depression. Biol Psychiatry, 67(5), 446–57. https://doi.org/10.1016/j.biopsych.2009.09.033
• Osimo, E. F., Baxter, L. J., Lewis, G., Jones, P. B., & Khandaker, G. M. (2019). Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med, 49(12), 1958–1970. https://doi.org/10.1017/S0033291719001454
• Khandaker, G. M., Pearson, R. M., Zammit, S., Lewis, G., & Jones, P. B. (2014). Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitudinal study. JAMA Psychiatry, 71(10), 1121–8. https://doi.org/10.1001/jamapsychiatry.2014.1332
• Watson, K. T., Simard, J. F., Henderson, V. W., Nutkiewicz, L., Lamers, F., Nasca, C., Rasgon, N., & Penninx, B. W. J. H. (2021). Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study. Am J Psychiatry, 178(10), 914–920. https://doi.org/10.1176/appi.ajp.2021.20101479
• Mezuk, B., Eaton, W. W., Albrecht, S., & Golden, S. H. (2008). Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care, 31(12), 2383–90. https://doi.org/10.2337/dc08-0985
• Gafoor, R., Booth, H. P., & Gulliford, M. C. (2018). Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. BMJ, 361, k1951. https://doi.org/10.1136/bmj.k1951
• Liang, Y., & Booker, C. (2024). Allostatic load and chronic pain: a prospective finding from the national survey of midlife development in the United States, 2004-2014. BMC Public Health, 24(1), 416. https://doi.org/10.1186/s12889-024-17888-1
• Cohen, S. P., Doshi, T. L., Kurihara, C., Reece, D., Dolomisiewicz, E., Phillips, C. R., Dawson, T., Jamison, D., Young, R., & Pasquina, P. F. (2021). Multicenter study evaluating factors associated with treatment outcome for low back pain injections. Regional Anesthesia and Pain Medicine, 47(2), 89–99. https://doi.org/10.1136/rapm-2021-103247
• Generaal, E., Vogelzangs, N., Macfarlane, G. J., Geenen, R., Smit, J. H., de Geus, E. J., Dekker, J., & Penninx, B. W. (2017). Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up. J Pain, 18(2), 155–165. https://doi.org/10.1016/j.jpain.2016.10.010

Related reading

• Nerve Pain After Knee Replacement: What Testing Can and Cannot Show
• How to Lower Insulin Resistance: What Moves It, and How to Tell
• Laboratory Panels