@LucH said in High-dose thiamine troubleshooting:

@Mostlylurking
Thanks for your input. I really appreciate the comments. It emphasizes very well the efficacy / the value of HDT (high physiological dose).
I’d like to put this point into excerpt:
*) Why to give HDT?

When giving supra-physiological doses of thiamin to the cells, enzymes come back to normal operating state. (1)

=> We aim to increase the exchange through passive and active ways. The active way is made through enzyme transporters. The passive way is through cell membranes, if there aren’t too many blockers (from oxidative stress and chronic low-grade inflammation e.g.).

Well, this certainly is a gigantic caveat, isn't it? If ANYTHING disrupts oxidative metabolism, inflammation goes way up due to lactic acid increase. Any oxidative stress (from toxins like heavy metals, etc.) depletes thiamine which throws a ringer into oxidative metabolism.

We know that the traditional way of transport of B1 TPP (from food) is through gastrointestinal phosphatases, before reaching blood flood. This B1 was thought to be only a water-soluble vitamin. It’s not. TPP can also be transported across cell membranes (2) but likely less well absorbed than benfotiamine or TTFD.
TPP = thiamine pyrophosphate.
*) Why and when nutritional intake is not sufficient.

There's some research in the salmon fishing industry that you might find very interesting. When the salmon are exposed to more PUFA in their diet in relationship to thiamine availability their health suffers and the low ratio of thiamine to PUFA can cause the fry (baby salmon) hatch to die. The solution for the problem is to put thiamine in the water. links:
https://hmr.biomedcentral.com/articles/10.1186/s10152-020-00542-9

https://www.mdpi.com/2410-3888/9/2/58

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182616/

There seems to be better research for the salmon fishing industry than there is for human health.

If we read the conventional recommendations from authorities there is only a problem for 6% of the US population.

I suspect that the authorities came to that deduction via the WAG method.

(3) That’s what the blood tests mention. Right but what about your optimal energy level or your brain functioning? See here the difference of appreciation: an impaired metabolism with a metabolic disorder of thyroid or glycemia if left untreated (not perceived before it’s too late because the Gauss’s curve has said so). Traditional medicine sees the failure but doesn’t always / usually anticipate the problems from slow carburation. That’s just one example.

You are overly generous re. the abilities of traditional medicine. I'm much more of a cynic due to my own personal experiences with doctors. I agree; what about optimal oxidative metabolism and brain function? The health industry is beyond broken.

Gauss’s curve
Gauss curb 1.png
The Gauss's curve analogy here emphasizes the concept of the "tail end" of the curve, where about 5% of cases fall outside the normal range. In this context, it suggests that there's a small percentage of cases where the metabolic disorder isn't perceived until it's too late. ## Traditional medicine tends to focus on the majority of cases within the normal range and may overlook or underestimate the significance of these outliers.
So, while traditional medicine might not see a problem because the majority of cases appear normal, it fails to anticipate the issues that arise from the small percentage of cases where metabolic disorders aren't detected early. This leads to the problem being left untreated, as it's not recognized until it's already advanced.

My own experience has been that traditional medicine doesn't see the problem because they have not bothered to look. Most medical doctors are clueless when it comes to things like the Krebs cycle and what might go wrong. They are trained to prescribe pharmaceutical drugs; they get no education regarding vitamins/minerals.

In summary, the Gauss's curve illustrates how the small percentage of cases falling outside the normal range can be overlooked, leading to the problem being untreated until it reaches a critical stage.

If you happen to be on the far side of 60, you are more likely to be thiamine deficient because the gut tends to lose its ability to absorb thiamine. But doctors will take one look at your age and write off your symptoms as being caused by "aging".

Happily, thiamine is considered a safe supplement and the easiest way to test to see if you would benefit from supplementing it is to take some. Researching online is a good idea.

suggested videos:
Vitamin B1 Deficiency - Pharma Harma (it's short)
and
The Ultimate Crash Course on Vitamin B1 - Fatigue, Nerve Pain, Heart Disease & More (it's long but very good!)

Metabolic Block
Are you exposed to “stress” factors that block your assimilation for the brain? As already seen, “thiamine (vitamin B1) is critical for the metabolism of food into cellular energy or ATP. Without sufficient thiamine, cellular energy wanes, and with it, the capacity to maintain the energy to function declines. Chronic, unrelenting fatigue is a common characteristic of insufficient thiamine. At its root, fatigue is the physical manifestation of poor energy metabolism”. (4)

Your appropriate blood test is then not going to explain anything.

Here are some case reports mentioning the insufficiency of the DRI (Daily Recommended Intake).
Diabetes
The proportion of people with type 1 or type 2 diabetes who have poor thiamin status based on erythrocyte transketolase activity ranges from 17% to 79% in studies conducted to date [40]. In a study of 76 consecutive patients with type 1 or type 2 diabetes, for example, 8% had mild thiamin deficiency and 32% had moderate deficiency based on assays of the transketolase enzyme [33].
Heart failures
The rates of poor thiamin status in patients with heart failure have ranged in studies from 21% to 98% [47]. Explanations for this association include older age, comorbidities, insufficient dietary intake, treatment with diuretics, and frequent hospitalizations [48].
The authors of one study reported that 33% of 100 patients with chronic heart failure had thiamin deficiency compared to 12% of 50 healthy volunteers [49]. Rates of deficiency were even higher when the investigators excluded those who used thiamin supplements.
Alzheimer’s disease
Thiamin deficiency produces oxidative stress in neurons, death of neurons, loss of memory, plaque formation, and changes in glucose metabolism—all markers of Alzheimer’s disease. Autopsy studies have shown that transketolase and other thiamin-dependent enzymes have decreased activity in the brains of people with Alzheimer’s disease [52,53].
Few studies have assessed the prevalence of thiamin deficiency in people with Alzheimer’s disease. One of these studies found that 13% of 150 patients with cognitive impairment and acute-onset behavioral disturbances were considered thiamin deficient based on plasma levels [26].
Note: Analysis based on plasma level gives only indication on short term. And not what is burned or blocked further in the process of assimilation.
Maintenance and Performance of the Brain
As already seen, thiamine plays a key role in the maintenance of brain function: Thiamine diphosphate is a cofactor for several enzymes involved in glucose metabolism whereas thiamine triphosphate has distinct properties at the neuronal membrane. (5) We need different forms of B1 to optimize different functions, and particularly to reach effects onto mitochondrial respiration.

I think what we really need is for doctors to understand how common thiamine deficiency/functional blockage actually is and the damage/symptoms it causes. They do not find what they are not testing for. They are led to believe that possible thiamine deficiency was resolved decades ago via the addition of thiamine to refined grain products.

Sources and References

Elliot Overton How is B1 from food assimilated?
DOI: 10.1534/genetics.104.028605
Dietary thiamine (vitamin B1) consists mainly of thiamine pyrophosphate (TPP), which is transformed into thiamine by gastrointestinal phosphatases before absorption. It was believed that TPP itself cannot be transported across plasma membranes in significant amounts, which forms TPP from thiamine at the expense of ATP inside cells. (…) These observations indicate that, in contrast to expectation from previous evidence, TPP can be transported across cell membranes. We also find that thiamine supplementation partially rescues the phenotype of partial loss-of-function mutants of the Na/K ATPase, providing genetic evidence that thiamine absorption, and/or redistribution from the absorbing cells, requires the full activity of this enzyme.
=> Comment Luch: We need the transketolase enzyme to absorb well this type of B1 (TPP from food). To fully absorb the benefits of TPP, passive transport through membranes is required. The average daily thiamin intake from foods and supplements in adults age 20 and older is 4.89 mg. An analysis of data from the 2003–2006 National Health and Nutrition Examination Survey showed that only 6% of the U.S. population has a usual intake below the EAR.

Oh, dear.... I wonder if they took into account the population's intake of PUFA (see the salmon studies above).

https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/#h6
The World Health Organization recommends daily oral doses of 10 mg thiamin for a week, followed by 3–5 mg/daily for at least 6 weeks, to treat mild thiamin deficiency.

The WHO? That organization that is focused on population reduction? They call it "sustainable development" I think. It's part of Agenda 2030.

Dr. Chandler Marrs talking about Thiamin. April 2022
Introduction to a video, talking with Scott Scott Forsgren, FDN-P.
https://www.hormonesmatter.com/talking-about-thiamine/ Thiamine diphosphate is a cofactor for several enzymes involved in glucose metabolism whereas thiamine triphosphate has distinct properties at the neuronal membrane
https://mirzoune-ciboulette.forumactif.org/t2045-english-corner-anti-stress-neuro-protective-effects-of-thiamine-b1#29713

@tea yes for the calcium (I usually take some 20-30min after B1 HCL just because it’s a good time to let stomach acid deal with it).
I do find taking potassium bicarb w/ baking soda has helped a lot with higher dose thiamine (also took doing it for at least a couple days before i noticed a big difference)