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Vitamin D metabolites and the gut microbiome in older men (nature.com)
88 points by voisin on Dec 3, 2020 | hide | past | favorite | 51 comments



My takeaway is that the widespread measure of serum 25(OH)D represents the total Vitamin D reserve store while the rarely measured 1,25(OH)2D [2 in 2D should be subscript] represents the actual active level. It is low 1,25(OH)2D or a reduced ability to convert storage to active that is associated with a less diverse gut microbiome.

We may be over supplementing. To use a car analogy, our gas tank is overflowing and we are obsessed with the gauge reading Full while the gauge reading Empty is the critical measure.

What we need is a measure of how fast our 25(OH)D is depleted and what level represents an empty tank.


Lots of interesting details here. I’m struggling somewhat with the language since this isn’t my area, but it seems to be saying a few things.

First, this is a study of 80 year old men so YMMV.

Second, in that group, they found more sunlight didn’t seem to actually correlate with vitamin D activation. Regardless of how you got vitamin D, you got the benefits if you had the right gut bacteria.

This seems like good news, since there’s been some indication for a while that vitamin D supplementation can be hit or miss and sunlight may be better. This could be the missing factor.


What is a _healthy_ gut microbiome? And if it's not healthy, how to make it healthy?


I'm a former IBS sufferer and have found that carefully managing my gut health has massively improved my quality of life. It's not the most scientific approach, but generally speaking, your gut is probably reasonably healthy if:

* you do not experience intestinal discomfort on a regular basis

* you can eat a wide variety of foods without getting unexpected diarrhea or constipation (i.e. when eating foods that typically do not do this to a wide range of people)

* your bowel movements are consistent, complete, a good colour, not painful, not loose, not hard

* you are not overweight/underweight

And of course, you can help all of this along...

* basically never eat fast food if you can avoid it, especially shitty McD's ground beef

* avoid taking antibiotics unless you're really sick enough to need them they can wipe out your microbiome and set you back months or years of progress)

take supplemental calcium and vitamin D

* eat a wide variety of foods, including oily and spicy things; you can "train" your system to handle things by eating them in smaller quantities as you get started and then gradually eat more

* but avoid eating too wide a variety of foods in one meal as that's most likely to overwhelm the gut's capability to effectively digest things

* yogurt, cheese, fermented stuff of almost any sort (without alcohol) all seem to be beneficial

* while we're at it, make sure you get enough iron, from red meat and dark green veg!

It's anecdotal of course but you can find any number of studies supporting this stuff. For me, taking my diet seriously didn't mean restricting in any serious sense how _much_ I eat, or even _what_, so much as balancing things to ensure I don't overwhelm the system.

In 2017 I had to take antibiotics for something and it seriously set me back years, I was back to having a horrible time at least once or twice a week from things I had been eating no problem before, and only by late 2019 was I really feeling confident to go and eat, say, spicy Mexican food again. At this point in time I would have to be sick enough that I'd be missing months of work to take antibiotics again.


> take supplemental calcium

But if you're male, do not take too much... High calcium intake has been associated with an increased risk of advanced-stage and high-grade prostate cancer [1].

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266887/


Good point! I take a calcium/zinc pill about once a week, which probably helps keep me below that level.


> * avoid taking antibiotics unless you're really sick enough to need +1 on this. I had to take antibiotics for a strep throat infection. Before this, I could eat anything and never have a loose bowel movement. I had various gut issues for almost an year after I took the antibiotics. I used to feel like I had a very healthy gut before.


The consensus view is more vegetables and fiber, and less processed food.


Yes. It seems to be connected with the synthesis of short-chain fatty acids by gut bacteria. Beta-glucan is also helpful in this regard; sources include porridge oats, mushrooms and supplementation.


Agreed. Specifically, prebiotic foods & foods that contain cultures (such as yogurt) make most sense to me (as a layperson).


Fermented foods like Sauerkraut as well


I’m not an expert but from what I’ve read you don’t need to eat the biota to get them, you just need to make them a happy home and they’ll find their way into your gut.


My sense is that's right, but it makes it sounds a little too magical. It might be better to say that most of the strains you want to encourage are already present, but a diet with lots of fiber (aka 'prebiotics') will encourage the good strains to outcompete the bad strains. It's a pretty complex balance, there are also phages, and some fungi all mixed up in there.


It was a long time ago now but I remember reading an article about a researcher who tested his gut biome every day or so and it was amazing how quickly things change depending on what you eat.



How did you determine it worked?

Looks like it's just a single, patented, probiotic strain[0]

I did a very brief search and couldn't find any compelling information on it (not to say that such evidence doesn't exist).

[0] https://en.wikipedia.org/wiki/Bifidobacterium_longum


My IBS worsened and for several months I had recurring constipation and some abdominal pain keeping me awake in the night. I tried changing diet and several medicaments but no change. When starting Alflorex symptoms eased after a few days and were totally gone after a week. They say it typically takes longer. Can’t say it wasn’t a coincidence of course.


i'm not scientist, just independent researcher.

healthy means able to digest food, absorb nutrients, and handle foreigners without much immune system involvement.

i keep mine healthy by avoiding preservative chemicals and processed food in general, avoiding antibiotics unless i really need them (tick bite), fasting, eating fermented and rotting food, avoiding stress, eating dirt, swimming in ocean, not going overboard with cleanliness.

most bacterial infections with undesirable results, eg strep throat, resolve for me with a 2-day water fast supplemented with raw onion and garlic and lemon.

in addition to gut, there are biomes everywhere else. i don,t use soap or any other "products" on my body. i only use one soap for all my soapy needs, one made traditionally (bronners solid as of 2020)


Wait, just to be sure---you're saying you do eat rotting food and dirt?


not just any dirt, i have a system for it, and it is not a lot, just for biome diversity. it's a process and ritual which occupies most of an entire day.

https://www.sciencedaily.com/releases/2011/06/110602162820.h...

here is an interesting interview about biome culture from a raw meat diet guy (not what i eat)

https://www.vice.com/en/article/nnqw3q/this-guy-has-eaten-no...


Yes


As I understand it, we don't know. People in different areas have very different gut microbiomes and correlations with health outcomes are not the same between different populations... At least that was what I remember reading some years ago.


http://www.gapsdiet.com

in my research I was led here. But not sure on the accuracy but they seem to have methods.


This diet is well regarded in my research as well, and prescribed for people with inflammation problems. It also happens to look like the 1st week or so of any kind of elimination diet / partial fasting. I don't know if they are trying to sell something, but you can get the benefits without buying anything, so they don't seem like quacks to me.


This looks a lot like quackery. A miracle diet that will cure almost all ailments? Sounds too good to be true.

The author encourages parents to disregard Physician advice in favor of a vaguely formulated diet advice and expensive supplements, which the author sells. Also lots of enemas and no MMR vaccines.


Could someone explain the significance of these findings?

It's not remotely my area of expertise, and I'm having trouble seeing if/how this has any current or future clinical significance.


(I am not a scientist)

My interpretation is that your gut bacteria are vital for metabolizing Vitamin D and that you can take a lot of supplements but if your gut aint right it won't help.

Slightly related: I keep trying to identifty the recent report that essentially demonstrated a big calculation error in our societal wisdom regarding Vitamin D amounts - and that we need a LOT more than most people think. 2,000 - 5,000 IUD is like a fraction of it.

Edit, found it: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541280/

    A statistical error in the estimation of the recommended dietary allowance 
    (RDA) for vitamin D was recently discovered; in a correct analysis of the data 
    used by the Institute of Medicine, it was found that 8895 IU/d was needed for 97.5% 
    of individuals to achieve values ≥50 nmol/L.
and

    ....we call all responsible public health authorities to consider designating 
    as the recommended dietary allowance (i.e., the average daily level of intake 
    sufficient to meet the nutrient requirements of nearly all healthy people, 
    presuming minimal sun exposure) intake levels corresponding to those proposed 
    by the Endocrine Society Expert Committee (2011) as safe upper tolerable daily 
    intake doses for patients at risk for vitamin D deficiency (<50 nmol/L):  

    2000 IU for those <1 year of age, 
    4000 IU for those aged 1-18 years, 
    and 10 000 IU for those aged >18 years.
I wonder how these two concepts could relate. Do you need more Vit-D or do you just need a healthier environment for it to be metabolized?

I have been taking 10,000 IU every night for a week or so - going to keep cruising on it for a while to see how I feel.


Be careful. "Vitamin" D is actually a hormone that is fat-soluble which means it can build up too much in your body and cause a toxic effect and I know one person who that happened to.

The way to know you're ok at your current dosage is to take a blood test, ideally at least twice a year (summer and winter) so you can make sure you're not overdosing.

I haven't had a blood test in many years, so currently I am only on 3000 IU. It's a big difference, in one week I have 21,000 IU and you have 70,000 IU, I am only taking 30% of the dose you are.

Get a blood test!


Perhaps off-topic but my inner hacker finds it very upsetting that getting blood tests can be so cumbersome, despite being so important. Make an appointment, transit to the doctor's office, pay a bunch of money, wait for labs, wait for your doctor to explain and prescribe stuff to you. It's cumbersome enough to the point where the vast majority of humans aren't testing anywhere near the frequency they should, including myself.

I don't think running diagnostics on a human should be this hard, we run diagnostics on our apps, computers, cars more often than ourselves. I wonder if people are working on making this process a lot easier (or if it's even possible, I have zero knowledge of the space).


I paid $47 for this vitamin D test (via blood draw): https://www.lifeextension.com/lab-testing/itemlc081950/vitam... You get a doctor's prescription (from a Florida doctor, good for anywhere in the country) and instructions to go to your nearest Labcorp for a blood draw. So make sure you have a Labcorp near you.

Here are a few alternatives you can look into, mentioned in this discussion: https://news.ycombinator.com/item?id=15868143

[0]: https://www.privatemdlabs.com

[1]: http://www.directlabs.com/

[2]: https://www.walkinlab.com/

[3]: https://www.health-tests-direct.com/

[4]: https://www.personalabs.com/


Why should you even need doctor prescription for something like this? Week ago I just went to nearby lab and asked them to make a blood draw to verify my vitamin D levels and got results same day via email.


Can you tell us which lab? Did you contact them before hand?


Sorry for not being clear - I'm not in the US. I was just surprised you need a doctor prescription for something like that.


US doctors have a strong political presence through the AMA and maintain a monopoly on nearly every medical procedure, test, and many drugs. It's impossible to get anything without a doctor's prescription and it's usually impossible to get that prescription without a (paid) visit to their office.


These are definitely a step up than what I'm used to and I appreciate the effort put into the reply. I'm still naively hoping there will be a scifi-esque biometric scanner or finger-prick analyzer, as another commenter put it, some day ;)


It would be great to have very easy testing with a pin prick of blood. This dream is what kept Theranos going for so long, but hopefully that scandal does not scare off other people from trying.


Quest diagnostics will let you do it yourself. I am in the process of ordering a self-serve vit-d test and metabolic panel for about $150, no doctor referral required.

(I also dislike the limitations as I feel like people are more capable of helping themselves in a lot of these situations)


It's not hard.

Google "LabCorps" near you.

You can walk in and get a basic metabolic panel in about 15 minutes, with results the next day or two, for about $50, without a doctor. I use them for frequent STI testing.


Elizabeth Holmes founded a startup a while back to solve this problem...

It seems like it’s just tough because you generally need a fair amount of blood for each test. We could lose some of the bureaucracy but it seems hard to get away from human phlebotomists and lab techs.


well, Holmes effort was more of a con game than delivering actual solutions.


I use medichecks. I order the tests I want, a nurse comes and takes my blood at home, then a few days later I get results emailed to me and a brief rundown from a doctor that’s looked them over. If there’s any problems I can take it up with my GP, even that can be done online now.


Seriously. Gimme a finger-prick analyzer, eh?


Our most current understanding is that 7k iu is closest to optimal, and that previous recommendations were based on bad math.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541280/

While toxicity is a serious matter, the actual risk is generally overblown, since it requires truly heroic, sustained doses.

>The evidence is clear that vitamin D toxicity is one of the rarest medical conditions and is typically due to intentional or inadvertent intake of extremely high doses of vitamin D (usually in the range of 50,000-100,000 IU/d for months to years)

https://www.mayoclinicproceedings.org/article/S0025-6196(15)...


I'm trying to find the HN thread from a few months ago, where an HN-user's spouse (who is a physician focused on treating patients suffering Vitamin D toxicity) gave a stark warning that she has personally seen many (hundreds of) patients on ~5-10k IU/day intake hit toxicity because they did not measure their levels. Be careful! Definitely try to get a test for your levels, definitely consult a doctor if you can. If you can't, know that 5k+ can be too much for some people.

(For the record, I began taking 1-2k IU/day in March.)



Thanks for explaining.

This makes me wonder if there is a problem in my gut. I was on a 50k IU / week dose because of low vitamin D. It made no impact.

Being out in the sun, however, made a huge impact - so I get much more sunlight now and I'm fine. I wonder if the vitamin D issue correlates with largely indoor office work now vs farming of our ancestors and largely being outside.


I was prescribed 50,000 IU Vitamin D and told to take it once a week, and not take any other Vitamin D supplements while taking this. Everyone is different, just sharing my experience.


I would contact a doctor.

Vitamin D stores in your body can take a long time to build up, but if you store too much it can be a major problem.

You should at least consider an at home vitamin D test, I found a few online(that i didn't order in the end) that were selling for around $50.

If you're determined to do this yourself you should periodically use those tests to help keep yourself safe.

Source: I'm not a doctor.


I'm curious, do you take any form of K2 with your D3, or not? I've heard that it's beneficial as it helps prevent calcification from occurring in your veins and arteries.


> I have been taking 10,000 IU every night

It would be better to take it at lunch: from what I have read a long time ago it might affect your sleep if you take it late.


If you take 10,000IU because 8895IU is what gets 97.5% of people to 50nmol/L, you are basically assuming you need more supplement than 97.5% of people, which is highly unlikely. There are people "at risk" that have trouble metabolizing the supplement, but chances are you're not one of them.

You need to do blood tests. Don't take 10,000IU daily without consulting a doctor. The "generally considered safe" upper limit is 4000IU. You'll probably be fine with 2000IU. Too much Vitamin D can mess with your calcium and doses as low as 5000IU/daily over a few years have been reported to cause serious problems.




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