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Point of contact for the paper;
Corresponding Author
Niharika A. Duggal
Department of Inflammation and Aging, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham, UK
National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, Birmingham, UK
Correspondence:
Niharika A. Duggal (aroran@bham.ac.uk)
A mediocre study. They compared 6 weeks of
Ridiculously low EPA dose, too much inulin and kefir with different kind of fibers so that any comparison is meaningless.
The kefir and fiber blend: Chuckling Goat Ltd.
The synbiotic arm were given 170 ml kefir and 10 g of a prebiotic mix (supplied by Chucking Goat Ltd), consumed as a smoothie daily for 6 weeks.
Note that the composition below is for 100g but the serving size is 10g so it provides only 2.71g of fiber for 6.98g of carbs and 0.95g of sugar.
Not really impressive. I’m taking fiber and EPA and kefir (>250ml of my home made fresh kefir).
Funny. That’s my mix too: EPA, fiber, homemade kefir. Though I also use a very small amount of EPA (500mg pure EPA, no DHA).
Butyrate: The Microbiome’s Anti-Aging “Kill Switch” for Senescent Cell
I was never able to find a BHB supplement that I liked. So I have chosen to take C8 (caprylic acid) in my morning coffee Actually use a combo of C8 and C10 for immediate and sustained benefits. It actually tastes good in my coffee. I use the powdered form, and it tastes a lot like adding a creamer to my coffee.
Of course: “ketone esters provided the largest BHB ketone boost per serving.”
Summary of Differences
| Feature | C8 Supplementation | Direct BHB Supplementation |
|---|---|---|
| Action | Precursor; body produces BHB from C8 | Direct source of BHB |
| Speed | Slower to raise BHB levels (peak around 60-120 min) | Rapid BHB surge (peak around 30-60 min) |
| Effect Duration | More sustained elevation | Quicker return to baseline |
| Goal | Supports long-term fat adaptation and endogenous ketone production | Provides immediate exog |
Mostly at my age I look for supplements that have benefits for the brain:
C8 (caprylic acid) supplementation primarily benefits the brain by providing an alternative and rapid fuel source in the form of ketones and through direct neuroprotective effects, including enhanced mitochondrial function and potential anti-inflammatory action.
Key Brain Benefits
Summary
C8 supplementation offers significant brain benefits by providing a rapid, alternative fuel and directly supporting neural health and function. These effects can lead to enhanced mental performance and may also help mitigate cognitive decline in individuals with conditions that impair brain glucose metabolism. Ref
OK, there were problems with this study. Here is some more from an analysis of the paper (see below) but it would seem that the idea of a complex of prebiotic fibers, and specific goat-milk kefir (27 strains) (how do you make this???), might have some value. Below I’ve done a search for other probiotic mixtures that might be similar to the one used in the study, but that are sold commercially in the USA.
4. Novelty
- Magnitude of Effect: We already knew fermented foods were good (Wastyk et al., 2021). What is new is the effect size (d>1.0 for multiple markers) compared to the standard of care (Omega-3). Omega-3s failed to move the needle on IL-6 or SIRT2 in this comparison.
- Specific Synbiotic Formulation: This wasn’t just “yogurt.” It was a specific goat-milk kefir (27 strains) paired with a complex 18-fiber prebiotic mix (arabinoxylan, beta-glucans, etc.). This supports the “precision prebiotic” hypothesis—you need the right fuel for the right bugs.
5. Critical Limitations
- The Age Confound (Major): The study compares a younger Synbiotic cohort (18+) against an older Omega-3/Inulin cohort (60+). While the authors adjusted for age statistically, this is a dangerous comparison. Older adults have established immunosenescence and higher baseline inflammation. It is possible Omega-3s work better in younger people, or that the Synbiotic effect is exaggerated because younger systems are more plastic.
- Non-Blinded: Participants knew they were drinking a smoothie. The placebo effect on subjective well-being is irrelevant for serum markers, but lifestyle confounding (e.g., “I’m drinking this healthy smoothie, maybe I shouldn’t eat pizza”) is a risk.
- Short Duration: 6 weeks is sufficient for cytokine changes but insufficient to prove long-term remodeling of the immune system or colonization of the gut microbiome.
- Low Dosage of Omega-3: The Omega-3 group received only 500mg/day (165mg EPA / 110mg DHA). This is a clinically low dose. Most therapeutic longevity protocols recommend 2g-4g daily. Comparing a “nuclear” synbiotic intervention to a “homeopathic” dose of Omega-3 is a straw-man comparison [Confidence: High].
Market search identified that no single pre-mixed powder contains all 18 specific isolated fibers, as many are structural subclasses of one another (e.g., Arabinan and Galactan are often substructures of Pectin or Arabinogalactan; Xyloglucan is a hemicellulose).
However, Designs for Health PaleoFiber and Vibrant Health Green Vibrance contain the highest density of these specific compounds due to their use of complex whole-plant and gum sources.
Match Count: 12/18 (Direct & Source-Derived)
Why it wins: This formula is designed as a “complex fiber” blend. It uses 12 distinct plant sources that naturally cover the structural hemicelluloses (Arabinoxylan, Xylan, Mannan) which are rarely found as isolated ingredients.
Ingredient Mapping:
Arabinogalactan: Native to Acacia Gum (primary ingredient).
Arabinoxylan: Psyllium Husk is ~70% highly branched arabinoxylan.
Cellulose: Bamboo Fiber is almost pure cellulose.
Guar Gum: Explicitly included (Hydrolyzed Guar).
Inulin: Chicory Root Inulin.
Mannan: Glucomannan (Konjac root) and Guar (Galactomannan).
Pectin: Apple Pectin.
Arabinan / Galactan: Abundant side-chains in Apple Pectin and Acacia.
Xylan: Major component of Bamboo Fiber.
Hemicellulose: Comprised of the Psyllium, Bamboo, and Flax fibers.
Missing: Chitin, GOS, IMO, Resistant Starch (unless RS version), XOS, Xyloglucan.
| Rank | Product / Brand | Vendor | Total Weight | Total Price |
|---|---|---|---|---|
| 1 | PaleoFiber (Unflavored) | Designs for Health | 300 g (10.6 oz) | ~$46.00 |
Match Count: 11/18
Why it ranks high: While primarily a “Greens” powder, its fiber profile is chemically complex. It explicitly adds Larch Arabinogalactan, FOS, and Apple Pectin to a base of cereal grasses (Wheat/Oat/Barley) which are the industry’s primary sources of Arabinoxylan, Beta-Glucan, and Xylan.
Ingredient Mapping:
Arabinogalactan: Larch Arabinogalactan (ResistAid) + Acacia.
Beta-Glucan: Oat Grass + Beta-1,3/1,6-Glucan (Yeast).
FOS: Explicitly listed.
Pectin: Apple Fruit Powder.
Arabinoxylan / Xylan: The cell walls of Wheat Grass and Barley Grass.
Cellulose: Whole Grass Powders.
Galactan: From Pectin/Acacia sources.
Missing: Chitin, GOS, Guar Gum, IMO, Mannan (unless trace), Resistant Starch, XOS, Xyloglucan.
| Rank | Product / Brand | Vendor | Total Weight | Total Price |
|---|---|---|---|---|
| 2 | Green Vibrance | Vibrant Health | 358 g (12.6 oz) | ~$52.00 |
Match Count: 7/18 (But high specificity)
Why it ranks high: It is one of the few products to explicitly isolate and list Xylooligosaccharide (XOS) and multiple forms of Beta-Glucan. It is a “precision” prebiotic rather than a “whole food” blend.
Ingredient Mapping:
XOS: Xylooligosaccharide (rarely found in blends).
Arabinogalactan: Explicitly listed.
Beta-Glucan: (1,3/1,6 from Yeast) AND (1,3/1,4 from Oat).
Inulin: Explicitly listed.
Missing: Arabinan, Arabinoxylan, Cellulose, Chitin, FOS, Galactan, GOS, Guar Gum, IMO, Mannan, Pectin, Resistant Starch, Xyloglucan.
| Rank | Product / Brand | Vendor | Total Weight | Total Price |
|---|---|---|---|---|
| 3 | Kibow Fortis | Kibow Biotech | 120 g (4.2 oz) | ~$40.00 |
Match Count: 4/18 (High dosage, low variety)
Why it ranks: Included because it is the primary market source for Resistant Starch, which the above blends lack.
Ingredient Mapping:
Resistant Starch: Green Banana + Solnul (Potato).
Guar Gum: Hydrolyzed Guar (Sunfiber).
Cellulose: Vegetable fiber blend.
Missing: Almost all specific hemicelluloses (Arabinan, Xylan, etc.) and immune fibers (Beta-Glucan, Arabinogalactan).
| Rank | Product / Brand | Vendor | Total Weight | Total Price |
|---|---|---|---|---|
| 4 | Foundational Fiber | Supergut | 168 g (5.9 oz) | ~$34.00 |
To achieve near 100% coverage of your 18-ingredient list, no single powder exists. You must combine:
Interesting related study:
I’ve been on my “high-butyrate” diet for the past few months, and it seems to be working. This week’s blood test that included HS-CRP was at 0.3mg/L, so about as low as it goes (given the error bars of this test).
That is great news! Could you please share your updated protocol?
I know you were taking inulin and then added sun fiber and were looking at a bunch of other things…
My butyrate program:
10 grams of inulin in my coffee right now (recently ran out of SunFiber)
NOW Foods Supplement, 8 Billion Acidophilus & Bifidus, 1 per day, 68 mg,
Curcumin Phytosome 500 mg (Meriva) - Sustained Release per day,
Natural Factors Oil of Oregano, Carvacrol 144mg per day
and occasionally (couple times a week) fermented tea (Japanese/chinese).
Tim, could you share the brands your are using? I’ve been dealing with acid reflux recently and would like to see if I see similar relief as you’ve described.
John, could you elaborate on citrate and acid reflux? Is there any research or protocol you can point to?
I am just parroting what we already know from various AIs. But what happened to Akkermansia?
“Metabolic Health: Ameliorating insulin sensitivity and lowering plasma total cholesterol.
Weight Management: Reductions in body weight, fat mass, and hip circumference have been observed in clinical studies.
Gut Barrier Integrity: Strengthening the mucus layer and preventing “leaky gut” by improving the gut’s physical barrier.”
FWIW: I have taken probiotics on and off over the years and did not notice any subjective change. Lately I have been putting my probiotics in enteric-coated capsules before taking them. The difference is dramatic. I notice a big change: normalization of my poop
I especially notice a normalization of my stomach and lower digestive tract.
Currently I am taking Lactobacillus brevis, but when I finish the bottle, I will go back to Akkermansia, which I have tried before with no subjective result. But at the time I was taking Akkermansia, I wasn’t putting it in enteric-coated capsules.
“Gut microbiome homeostasis is fundamental to brain health (cognitive function and synaptic plasticity) (Salami, 2021), preventing neuroinflammation and protecting against neurodegenerative disorders in the elderly by maintaining microglial cells in a healthy mature state”
“Diversity & Stability: A healthy gut typically has a high variety of different species that are resilient enough to bounce back after temporary disruptions like a round of antibiotics or a change in diet.”
Where do you order enteric-coated capsules?
I searched before (a couple of years back) with no success.
I use tributyrin to reduce inflammation, not for acid reflux. To treat acid reflux combined with acidosis, I used to take 650-mg tablets of sodium bicarb for years. Recently, however, the sodium got to be too much and I switched to capsules of ginger. I take one 500-mg capsule three times a day with food. This works. It also obliterates inflammation.
Yes, John Hemming, you often post about citrate. What do you get out of it and what is a good starting dose?
Enteric caps are elusive to find . AI said it might be because true enteric implies “medical” as opposed to simple supplements. Sometimes on Amazon XPRS has enteric and also Leadlife. I tested both in vinegar and both brands preformed well. Enteric (Acid-Resistant) Clear Empty Gelatin Capsules — 1000 ct (Sizes 00-1)
This has some interesting content on the topic and product as well:
There seems to be many different products on the market containing Tributyrin with various other ingredients. I wonder if it would be more beneficial to alternate various products.
Here’s a paper about how resistant starch is linked to increased TMAO in plasma:
Resistant starch is widely celebrated in biotech, healthcare, and longevity circles for its ability to blunt insulin spikes and feed the colonic microbiome. However, a meticulously controlled dietary trial challenges this universally positive narrative, revealing that high intake of resistant starch can significantly elevate trimethylamine-N-oxide (TMAO), a gut-derived metabolite tightly linked to cardiovascular disease risk.
Conducted by researchers across several US institutions, including the Children’s Hospital Oakland Research Institute and Lawrence Berkeley National Laboratory, this trial investigated how diets varying in resistant starch and total carbohydrate content affect postprandial glucose and TMAO levels. The research was published in the British Journal of Nutrition. The impact score of this journal is 3.0, evaluated against a typical high-end range of 0–15 for top nutrition science journals, therefore this is a Medium impact journal.
In a rigorously controlled cross-over trial, 52 healthy men and women were assigned to lower-carbohydrate (39-40% of energy) or higher-carbohydrate (51-53% of energy) dietary arms. Within these arms, participants consumed 2-week diets that were either high or low in resistant starch, separated by a 2-week washout. The findings present a striking metabolic trade-off. As expected, the high-resistant-starch meals successfully reduced postprandial insulin and glucose responses, demonstrating clear utility for meal-to-meal glycemic control. However, in the lower-carbohydrate context, the high-resistant-starch diet unexpectedly increased fasting plasma levels of TMAO and its precursors, including carnitine and betaine. When overall carbohydrate intake was high, TMAO levels were uniformly elevated regardless of starch digestibility, suggesting that baseline carbohydrate load dictates microbial fermentation pathways. Crucially, the short-term resistant starch intervention failed to improve fasting lipids, lipoproteins, or baseline insulin sensitivity.
This study complicates the established consensus on resistant starch. It suggests that while swapping digestible carbohydrates for resistant starch improves immediate glycemic markers, it simultaneously shifts colonic microbial fermentation in a way that ramps up pro-atherogenic TMAO production. For longevity specialists prioritizing actionable insights, this highlights a critical biological reality: single-variable nutritional interventions often produce competing multi-system trade-offs, pitting cardiovascular and metabolic pathways against one another.