Vitamin B1 (thiamine) megadosing can massively reduce fatigue, in many cases reversing it entirely.

(🧵1/20)

This study was a small pilot study conducted about a decade ago.

Anywhere from 600-1500 mg of B1 was used, depending on the weight of the patient.

The results were stunning.

10/12 patients had a complete reversal of fatigue.

The other two saw reductions by 50% and 66%.

(2/20)

What was stunning about this study was that these people did not have thiamine (B1) deficiency,

yet they responded to thiamine megadoses as if they were.

This is likely because measuring the amount of B1 or its active metabolite, TPP, is not sufficient to tell if someone gets enough of it into their cells, where it exerts its effects.

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They suggest that certain genetic abnormalities of the thiamine (B1) transporters can be an issue.

Even if thiamine is normal in the blood, that doesn't mean it gets into cells where it helps.

Megadosing circumvents this.

(4/20)

Another study showed similar benefits in stroke patients at 600 mg per day.

Keep in mind this is >100X the normal amount you'd get in your diet.

These people showed fatigue reductions by ~75%.

(5/20)

Once again, there was no overt thiamine deficiency, at least as it is classically defined.

It's vital to not judge blood tests at face value.

You need to understand what its measuring in the big picture.

(6/20)

Thiamine (B1) megadosing (600-1500 mg/day) cuts fatigue nearly in half.

Here it was in patients with MS, 75% of whom often struggle with fatigue.

(7/20)

B1 megadosing also improved:

➜ Heat intolerance
➜ Sleep
➜ Depression
➜ Anxiety
➜ Irritability
➜ Dry skin
➜ Water retention
➜ High heart rate (tachycardia)

with NO side effects.

(8/20)

Thiamine megadosing also improves fatigue (& pain) in fibromyalgia.

Fatigue down 56.4%.

Pain down 63.3%.

(9/20)

Once again, improvement with these massive thiamine doses did not depend on underlying deficiency.

Some patients did not report any improvement until the dose was upped to around 1500 mg per day!

(10/20)

Most of these are small studies or case reports, but more recent studies continue to show thiamine's prowess.

For example, a 2020 paper in people with IBD showed thiamine doses, anywhere from 600-1800 mg of thiamine HCl, had huge benefits for fatigue.

G1 here had B1 the first 4 weeks, then nothing, then placebo weeks 8-12

G2 had placebo the first 4, then nothing, then B1 weeks 8-12

You can see that when either group had thiamine, it resulted in huge benefits.

(11/20)

Another recent study showed lower doses of thiamine can help with fatigue as well.

However, at these lower doses (300 mg), people needed to take it for 6+ months in order to see a benefit.

This can be fast tracked with higher doses.

(12/20)

In fact, thiamine can mimic & outperform many of the benefits of exercise.

Here, a huge dose of TTFD, a form of B1 lowered:

➥ Lactate - a driver of muscle fatigue and a sign of inefficient metabolism
➥ Ammonia - a toxic byproduct of protein metabolism

People taking thiamine had similar performance in bicycle exercise as people literally training for it without thiamine.

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Vitamin B1 (Thiamine) is so important because it helps churn out energy in cells.

Enzymes like:

• Pyruvate dehydrogenase → central in carb metabolism
• α-KG dehydrogenase → Krebs cycle (all nutrients)
• Transketolase → antioxidant + detox power
• BCKDC → breaks down BCAAs for energy

all require the activated form of vitamin B1 (TPP).

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Thiamine most notably is important for GLUCOSE metabolism.

One of the most vital steps in the metabolism of glucose is the conversion of a molecule called pyruvate into acetyl-coA.

This conversion is needed to get the most energy (30-32 ATP vs 2-7 without) out of glucose.

If your mitochondria are only harvesting a fraction of their energy from the food you eat, of course you will feel low energy.

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Thiamine (B1) dependent metabolic reactions are also vital for maintaining a good NAD+/NADH ratio, which is vitally important for allowing cells to continue to burn energy.

(16/20)

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Another important function of thiamine is to fuel the pentose phosphate pathway, as it required for the enzyme transketolase.

This pathway replenishes NADPH, which is vital for recycling glutathione, our master antioxidant / detoxifying agent.

Without it, you could be bogged down by toxins and free radical damage, both of which can contribute to fatigue.

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NADPH, formed with the help of B1, is also needed to synthesize various neurotransmitters.

Notably, it helps pump out dopamine and norepinephrine, both of which boost movement, motivation, and subjective energy levels.

(18/20)

There are multiple forms of thiamine that can allow you to take less for similar benefits.

Side effects reported in these studies were incredibly rare, such as elevated heart rate, which subsides immediately.

(19/20)

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In summary:

Thiamine (Vitamin B1) Megadosing & Fatigue:

◇ Pilot study: 600–1500 mg/day → 10/12 had full fatigue reversal, others improved 50–66%
◇ Not deficiency-driven: Benefits despite normal blood thiamine → likely transporter/genetic issues → megadosing bypasses
◇ Stroke patients: 600 mg/day reduced fatigue by ~75%
◇ MS patients: 600–1500 mg/day cut fatigue ~50%; also improved heat intolerance, sleep, mood, skin, water retention, tachycardia — no side effects
◇ Fibromyalgia: Fatigue ↓56.4%, pain ↓63.3% (some only responded at ~1500 mg/day)
◇ IBD (2020 study): 600–1800 mg/day showed large fatigue reductions, placebo-controlled crossover confirmed effects
◇ Lower doses (300 mg): Effective but require 6+ months; high doses act faster
◇ Performance: High-dose TTFD lowered lactate & ammonia → mimicked/exceeded exercise training in metabolic benefits

Why Thiamine Works (Mechanisms):

◇ Key enzymes: Pyruvate dehydrogenase, α-KG dehydrogenase, Transketolase, BCKDC
◇ Energy: Enables full glucose oxidation (30–32 ATP vs 2–7 without)
◇ Redox balance: Supports NAD+/NADH ratio for sustained energy
◇ Antioxidant defense: Fuels PPP → NADPH → regenerates glutathione
◇ Neurotransmitters: NADPH needed for dopamine & norepinephrine synthesis → boosts drive, motivation, energy

It's a simple, easy and cheap way to address this, low risk, high reward.

(20/20)