Acarbose is on the way with my first order of Rapamycin and one reason I ordered it is for it’s beneficial effect on the gut microbiome. Akkermansia is usually present in healthy amounts in lean people and in deficient amounts in overweight people. I’m lean and take good care of my gut microbiome. I also eat yogurt with Bifidobacterium animalis which along with a prebiotic fiber (I use inulin) is known to boost akkermansia. I’ve been taking Metformin for awhile and my glucose control isn’t bad, I was really just referring to the glucose spikes that are known to be detrimental. On Akkermansia see this study:
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Might be with doing a gut biome test so see what your akk levels are.
You know I’m all for more testing to get a baseline before starting rapamycin. But I’ve been building my list of tests - starting of course with a complete blood test (to which I now have many add-ons). I also want to do a DexaScan and a Vo2 Max test. Also OmegaQuant. I just totaled up the cost and it’s getting right up there. I couldn’t find any Gut biome test under $100 USD so I may have to skip that one.
Hear you - cost can easily run away on these things.
Good paper confirming amlodipine’s unique benefits: Amlodipine in the current management of hypertension 2023
Amlodipine has low renal clearance (7 mL/min/mg) and long half-life (35–50 h) and duration of action, which allows it to sustain its anti-hypertensive effect for more than 24 h following a single dose. Additionally, blood pressure (BP) control is maintained even when a dose has been missed, providing continuous protection in case of incidental noncompliance. It has proven to reduce BP variability and successfully lower BP. Amlodipine also controls BP in patients with a systolic/diastolic BP of 130/80 mm Hg or higher, diabetes, or chronic kidney disease without worsening glycemic or kidney function. Additionally, amlodipine is a wise choice for older adults due to its ability to control BP and protect against stroke and myocardial infarction. Side effects of amlodipine include edema, palpitations, dizziness, and flushing, which are more common with the higher dose of 10 mg.
(ping @DrFraser, thought you might be interested)
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Indeed - unless there is a reason against this in an individual patient, once I get to 40 mg of Telmisartan, the amlodipine is next for exactly that reason then indapamide as third agent. The side effects usually occur once pushing higher dose on amlodipine, and I generally don’t go beyond 5 mg. Peripheral edema seems the most common side effect, and then I’d just change to extended release diltiazem (another CCB).
The other interesting area of evidence is better outcomes in patients who take their meds at bedtime rather than AM - so I advise this also.
Every patient has individual factors that might have this modified, but that is my general approach, and tend to goal systolic ~115 mmHg for most people. As people get quite old (which each year I advance my definition of that forward by 1 year), letting than run a bit higher, is probably without any additional mortality risk.
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This is an interesting area, as I like to test things that are truly actionable and would modify what I have someone do. The tests like Genova’s GI Effects are amazing https://www.gdx.net/products/gi-effects - the question is what impact does this have on what is advised to a patient, beyond what I’d be advising anyway? In patient’s not improving, despite normal advice - sure I’ll add this.
I really like the KBMO 176 FIT test https://kbmodiagnostics.com/wp-content/uploads/FIT-176_Patient_Report_Example_2023.pdf which has a sample report.
Ultimately, gut health is really important, and having fiber at least 40 grams/day (we have ~70) and having diversity of >35 vege/plant/seeds/nuts per week (we have that every day) will have your gut bacteria move to optimal (for most people). Small changes over time are important as rapid changes will cause problems as various strains of bacteria become less popular and others more.
The KBMO test essentially tells you if you have altered gut permeability (through zonulin and less so occludin) and whether you are getting reactions to the gram negative bacteria cells getting into gut wall and blood stream (through IgA and IgG antibodies respectively). Then the issue becomes food sensitivities which you can see what things might be causing inflammation in your diet, and might want to be avoided. If no altered gut permeability, then no reason to change things.
The Akkermansia is interesting - I’m not overly convinced that supplementation makes any long term change, but once in a healthy dietary pattern and stable, putting some in, might be worthwhile? The challenge is that in standard doses like 10 billion CFU’s per day, this will take 100 days to have these total ~1% of your microbiome in your gut – and I suspect, if environment isn’t ideal, they all get out competed by your other gut bacteria and get eliminated.
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If GMRx2 is approved in the future (see here for more details: Optimal Blood Pressure we Should Target? Systolic Under 110 or 100? - #222 by adssx ), would you instead start directly with the low-dose triple combination telmisartan 10 mg + amlodipine 1.25 mg + indapamide 0.625 mg?
Also: how come indapamide is not more frequently used? It’s not even in the top 300 in the US. People thought that chlorthalidone was better than HCTZ, but the large VA trial failed to show any benefits (Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events 2022). Could it lead practicians to re-evaluate their choice and prescribe indapamide instead of chlorthalidone?
However, this paper says: “There were no detectable differences between HCTZ and INDAP in metabolic adverse effects, including effects on serum potassium. In conclusion, these head-to-head comparisons demonstrate that, like chlorthalidone, INDAP is more potent than HCTZ at commonly prescribed doses without evidence for greater adverse metabolic effects.” (Head-to-Head Comparisons of Hydrochlorothiazide With Indapamide and Chlorthalidone Antihypertensive and Metabolic Effects 2015)
Indapamide (1.5 mg) sustained release (SR) might be even better than indapamide immediate release:
- Indapamide SR Versus Candesartan and Amlodipine in Hypertension: The X-CELLENT Study 2006
- A comparison of indapamide SR 1.5 mg with both amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients: a randomized double-blind controlled study
- Clinical Positioning of Indapamide Sustained Release 1.5mg in Management Protocols for Hypertension 2000
@DrFraser Is there any use for antibiotics to “reset” the gut before a diet shift (more fiber, more diversity) plus probiotics to seed the good bugs?
Overall, the tolerability of medications in many people seems to relate to how much you block a given pathway you are focusing on. This is why just a touch of antagonism to several pathways if often better tolerated and more effective than going after any single pathway.
As an aside, a natural product Hawthorne Berry Extract seems to have Digitalis, CCB, Beta Blocker, Ace-Inhibitor, AMPK action, increasing SOB and nitric oxide and possibly even decreasing lipids. There are even more proposed benefits of this compound - but I do see some patients do remarkably well on this while not tolerating standard pharmaceuticals.
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Hi Joseph,
Antibiotics will wipe out good and bad bacteria, it is the nuclear option.
Best to work with what you have, and make changes slowly, to slowly migrate toward a better microbiome. But yes, big changes rapidly will cause GI distress in many patients - but doing something like increasing fiber by 5 mg/day for a week, then another 5 mg/day for another week. Slowly adding diversity - it is a process over 2-3 months.
There are folks who research in this area who do not think probiotics make any difference - it is a drop in the bucket, and most are eliminated by your solid microbiome rapidly.
Dr. B on Zoe does a great job discussing (don’t waste your time with Dr. Spector on this one - but Dr. B has his facts right).
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Thanks. This quote above is why I was wondering about the antibiotics. My gut and diet are very good now but my supplementation of Akkermansia is coming to an end after 3 months. It was a bit of a shock to my system for a few weeks but I also found that my HbA1c fell by 0.5 to 5.0 (after only 2 months of Akkermansia) which is a lifetime low for me. I’d like to keep the Akkermansia living in my gut (which I suppose was missing since I had a big improvement; I did not test).
My plan is just to see what happens after I stop the Akkermansia but continue my high fiber, diverse diet. But I was thinking about plan B.
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Pendulum who have been the proponent of this, at least commercially seem to think there is some GLP1 agonist like activity with the bacteria.
So yes, it does have evidence for benefit while being taken.
As somewhat of an aside, the company Z biotic makes a gut bacteria that for 24 hrs stays around long enough to eliminate, I believe acetaldehyde from ethanol ingestion, such that there is no hangover.
However it only has enough activity to work max 24 hours. Your normal micro biome eliminates it enough for it to not work longer.
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Yep Dr. B is headed to the dark side selling something. He’s in all fairness pretty good, so at least I think it is likely a good product. Would be better just to eat the whole foods - but not everyone is going to.
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What’s the name of the supplement, available on Amazon?
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I think you have to buy from his website. Or you can assemble the ingredients yourself.
Ok, thanks - but who is “Dr. B” I went up several messages above but get lost without seeing who that is?
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Dr B is Dr William Bulsiewicz @theguthealthmd
a qualified MD, board-certified in internal medicine and gastroenterology, a Master of Science in Clinical Investigation, and was chief gastroenterology fellow at UNC
I know him from his podcasting. He is an excellent speaker. If anyone knows how to heal the gut, he would be the one. The website to buy his stuff is 38tera.com. It is a high functioning commercial website. Hide your wallet if you visit.
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Blood pressure is super nuanced and context is very important. Increased pulse pressure for example can either mean arteriosclerosis and diffuse vascular stiffening or indication of increased cardiac output in young athletes.
When I was at my peak racing performance, I couldn’t stand up without getting dizzy.
These days due low salt, high dietary potassium/Mg and continued 10-12 hours/week of mixed exercise I tend to run circa 115/65 which fits the high cardiac output, relaxed artery and low plasma osmolarity pattern.
BTW, on big endurance hot days I increase my salt quite a bit. Inadequate electrolyte replacement along with dehydration is a literal suicide in the Arizona desert especially when superimposed on heat exhaustion.
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