#141

It’s a challenging area to make recommendations for sure. I recently complete my A4M Cardiology Fellowship with Mark Houston and he now makes sure folks are 70-90 ng/mL. I appreciate some of this may be his preference and not the greatest evidence base. Along with this, it seems safe to be 70-90 ng/mL on your Vitamin D, so I’ll go with his advice until I find evidence otherwise. Too many things we do don’t have clear evidence to support them.

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#142

@DrFraser Have you considered the following in your anti dementia protocol?

  1. Beta-Hydroxy Beta-Methylbutyrate
  2. exogenous ketones or Mediterranean keto diet if the patient can comply
  3. intranasal rifampicin & resveratrol
  4. trehalose as a sugar replacement
  5. modified citrus pectin
  6. plasmalogen supplementation
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#143

5000 IUs a day takes me to 30. I need 10,000 IUs to go to 40-60 and that’s with vitamin K.

I would recommend that if you take 10,000 IUs that you get tested for vitamin D levels though.

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#144
  • researchers identified two possible ways these bacteria may impact brain health. This includes harmful bacteria directly entering the bloodstream, potentially causing damage to the brain. Alternatively, an imbalance between beneficial and harmful bacteria can reduce the conversion of nitrate (abundant in vegetable-rich diets) to nitric oxide —a chemical crucial for brain communication and memory formation.
#145

I am with @DrFraser on this.

My own experimentation has found that the body will convert quite a high proportion of up to 3,000 iu per day, but it does not do so well with higher daily doses. I am not sure what happens to the extra cholecacliferol that does not end up as 25OHD. My view from personal experimentation is that if unconverted or converted to whatever it is converted to in a waste form it is mildly toxic. Hence I take a small amount of dedrogyl which is a form of 25OHD to keep my levels to around 200nmol/L (which in US units is 80ng/ml).

I track 25OHD in my weekly blood tests so I know the balance between different inputs and the serum level.

My mechanistic hypothesis is that the genes which depend on 25OHD (with the VDR as a transcription factor) are more frequently transcribed with the higher level. I did by mistake get up to 419 nmol/L, stopped supplementing when I found this out and a week later was on 337 and then a week after that on 209 (divide by 2.5 for US units).

My evolutionary hypothesis is that vitamin D systems evolved to prevent animals from needing more food (for protein production) in the winter and early spring. Hence the genes that are expressed are useful, but not immediately essential for life. Obviously it has more function than genetic, but with about 1,000 genes having the VDR as a transcription factor that’s quite a part of the genome.

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#146

I considered those and of the ones there, the one I need to add for sure is exogenous ketones.

KetoneAid (or for folks wanting a bit of intoxication) Ketohol seems to make a difference in some individuals with MCI or early AD. I’m not sure it prevents dementia which is what my focus is. At the point you have AD, the game is somewhat over - very difficult to reverse. I’m looking at identifying individuals at risk and pre-emptively recommending a host of items to risk reduce.

I’m yet to see good evidence for the other items you mention (except trehalose) in this context. This probably is my lack of reviewing the literature, and if you know of some, I’d love to be educated and have the opportunity to revise my protocol.

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#147

Interestingly, I’m increasingly sending off oral microbiome tests on individuals. Getting a look at P gingivalis and so many other pathogens is useful and not that expensive.

Here is a sample of what the report covers.

Oral Microbiome Profile Sample Report.pdf (422.7 KB)

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#148

How do you treat it differentially to fix oral microbiome besides brush and floss. If its bad do you nuke it with alcohol mouthwash?

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#149

There’s a few other things to look at, depending on the findings. Obviously tongue scraping is huge, but also diet changes may be required. I’ve heard of the use of probiotic toothpaste and mouthwash, but I have no idea of their efficacy. Also avoiding fluoride can help.

Also, bad dentistry can be a culprit. Bad root canals that potentially become havens for bad microbiota and unchecked inflammation.

Also, there is a lot of cross-talk between the gut and oral microbiome, so issues that come up in the oral microbiome report may point to other gut issues that need to be resolved.

#150

@DrFraser I’ve been reading about xylitol as an aid in oral microbiome health. The other thing I read that hit me like a ton of bricks is to not be continuously drinking fluids during the day. (I tend to drink teas non-stop!)

Any truth to these ideas?

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#151

That makes me think maybe its good to have low vit d one month a year to hibernate and rest those systems since their not designed to never stop. Similar to people who do a big fast once a year or mayo clinic fisetin senylitic protocol

#152

This is a really good question, which calls into play why test if the advice is going to be what should be done anyway? This also comes up with gut microbiome tests.

My experience of how this plays out, is when there is something that comes up as a concern on these tests, we do implement strategies to normalize and then retest to confirm.

Mouth wash is generally not the best idea (at least ones with alcohol) as they indiscriminately kill everything and then you have no microbiome.

It should be noted that p gingivalis is pretty clever and creates a biofilm making it hard to eradicate, which is why mechanical repetitive cleaning is part of the strategy.

Things I look at for p gingivalis include:

  1. very frequent tooth and gum brushing with a high quality electric toothbrush
  2. Waterpik or flossing or both at least twice daily.
  3. On have a diagnosis of p gingivalis, as it tends to be protected under a biofilm - best to get a professional dental cleaning.
  4. Consider a probiotic meant to improve oral microbiome such as one of these:
    Probiomax Oral or Biogaia.
  5. Xylitol (thanks @约瑟夫_拉维尔) is a sensible addition
  6. If oral hygiene is excellent and we enact these items above and still testing positive, then:
    -Consider short course of chlorhexidine mouthwash
    -Consider short course of metronidazole (doxycycline, amoxicillin, and azithromycin also work, but have more effect on the other oral bacteria, whereas metronidazole is a little more limited in its reach)
    -Add Turmeric based toothpaste
  7. Retest post therapy.

These would all be general approaches - not medical advice - naturally your doctor/dentist should be consulted, but this is one approach.

4 Likes
#153

Indeed you may be right.

1 Like
#154

DrFraser,

I’ve been taking 10,000 IU vitamin D3 + 50 mg K2 (MK-4) + 1 mg K2 (MK-7) daily for about 10 years. My blood tests have always been fine with vitamin D levels generally between 80 and 90 ng/ml.

By the way, I’ve been wondering in what way you would use methylene blue in your protocol.

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#155

Is that in ng/ml or nmol/l?

#156

The post has been revised to show ng/ml.

#157

Thanks. I thought that was probably the case. I find 3,000 iu will maintain about 90 nmol/L viz 36 ng/ml.

Your MK4 and MK7 figures seem higher than many. Is there a reason for that?

#158

Yes a reasonable % of people need >5,000 IU of D3 daily to achieve a vitamin D in the range of >40 ng/mL. It is however important to take K2 with it, especially if pushing the doses up. Also, given that the upper limit of normal on most assays is 100 ng/mL, being close to that would generally be a reason to check periodically to make sure you aren’t pushing above 100 ng/mL

I’ll put in my standard instructions for methylene blue for my patient’s below. Naturally discuss with your primary care physician or other licensed professional.
Methylene Blue
First, make sure you not on any SSRI or MAO-I antidepressants. Second, with low dose Methylene Blue, it is unlikely, even if you have a G6PD Deficiency that you would not get into trouble – but this compound can cause your red blood cells to “hemolyze” or break down, which can be serious. Especially if you are of Mediterranean or African descent, get this tested (blood test) before starting Methylene Blue. Interesting videos to watch below:

A trial of Methylene Blue is primarily guided by whether this adds mental clarity and decreases fatigue – if so, continue.

Dosing:
Generally start with 8-12 mg each morning (which is often a sufficient daily dose for many people), after 1 week if doing well, and if you have a sense of energy not being optimal later in the day, you can choose to add a second dose around lunch (generally 5-6 hours after your morning dose, but not close to going to bed). If you work out first thing in the morning, generally wait to take this until right after your workout.

Select from:
Nutricel Blue Boost 12 mg. Amazon.com: Methylene Blue (USP Grade) Supplements, Capsule Form, with Added Vitamin C Ester for Enhanced Absorption, Brain Supplement with ATP Fuel for Memory, Focus, Clarity, Cognition, Energy : Health & Household
The advantage of this, is it is encapsulated, so no blue tongue/teeth, but a fixed dose of 12 mg.
Tro Just Blue. Just Blue™ – Troscriptions® Code: FRASER gets your 10% off
The advantage of this is a wafer that can be broken into 4 mg doses. The downside is 4 wafers (16 x 4 mg dose) on subscribe and save ends up being $23 for not very many mg. These can be swallowed or dissolved in the mouth, but allow for smaller doses or adjustments. If starting with these, can start as low as a 4 mg, and gradually go up.

3 Likes
#159

Reminder: Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies 2024

Of 9,267 identified literatures, 23 were eligible for inclusion in the meta-analyses, among which 9 and 4 literatures were included in the dose-response analyses for the risk of dementia and Alzheimer’s disease (AD). Vitamin D deficiency exhibited a 1.42 times risk for dementia (95% confidence interval (CI) = 1.21–1.65) and a 1.57-fold excess risk for AD (95% CI = 1.15–2.14). And vitamin D deficiency was associated with 34% elevated risk with cognitive impairment (95% CI = 1.19–1.52). Additionally, vitamin D was non-linearly related to the risk of dementia (pnonlinearity = 0.0000) and AD (pnonlinearity = 0.0042). The approximate 77.5–100 nmol/L 25-hydroxyvitamin D [25(OH)D] was optimal for reducing dementia risk. And the AD risk seemed to be decreased when the 25(OH)D level >40.1 nmol/L.

77.5–100 nmol/L of vitamin D means between 31 and 40 ng/mL. I’m not sure recommending a higher level is evidence-based @DrFraser. See also: Vitamin D supplementation worsens Alzheimer’s progression: Animal model and human cohort studies 2022

Consistently, our population-based longitudinal study also showed that dementia-free older adults (n = 14,648) taking vitamin D3 supplements for over 146 days/year were 1.8 times more likely to develop dementia than those not taking the supplements. Among those with pre-existing dementia (n = 980), those taking vitamin D3 supplements for over 146 days/year had 2.17 times the risk of mortality than those not taking the supplements.

That being said APOE4 non-carrier females might benefit from it per Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status 2023?

4 Likes
#160

This has the interesting point that I found with N=1 experimentation a few years ago. If I supplemented with 3,000iu vitamin D I slept better than supplementing with 6,000iu. I also experimented with bolus doses.

The body will have a limited rate at which it can turn Cholecalciferol into 25 Hydroxy Vitamin D (which is what is measured in serum and is the stored form of Vitamin D3. The body converts this into 1,25 Di Hydroxy Vitamin D for the active form and also 24,25 DiHydroxyVitamin D about which there was a debate a few years ago, but I have not studied this.

I think either
a) Unconverted Cholecalciferol disrupts sleep in some way (hence is mildly toxic) or
b) A disposal pathway of excess Cholecalciferol disrupts sleep.

Either way higher supplementation would be likely to make things that depend on good sleep worse.

What I personally do to keep my 25OHD levels high is to supplement with 25OHD.

I have seen research which used a bolus dose of 50,000 iu once a month. That also would be potentially harmful and in fact it found that vitamin D was not much use (or slightly harmful).

This is one of those subtle things where precisely what people do makes a real difference.

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