The Thiamine Bible

A long look at the overlooked nutrient behind energy, mood, performance, digestion, fatty liver, and the way sugar is actually handled

People argue about carbs, insulin, cravings, ancestral diets, blood sugar, satiety, sugar highs and crashes. But there is one crucial question that must be asked before anything else.

“Once glucose enters your body, can it actually be carried all the way for efficient burning?”

Can it produce CO2, ATP, heat, drive, and usable life? Or does it stall halfway, become lactate, and push the body into a more stressed state?

That junction is extremely important. It decides whether meals feel like nourishment or punishment, whether a meal leaves someone warm and mentally clear or irritable and tired.

Few nutrients matter more at this junction than thiamine (B1).

That is why thiamine leads to such disproportionate success stories in many people.

In the medical context it looks quite boring, with it being a vitamin only associated with deficiency states.

In other settings it looks absurdly powerful, showing up in conversations about fatigue, mood, exercise, blood sugar, Parkinson’s and Alzheimer’s disease, fatty liver, and even cancer metabolism.

The reason for the second context is that the chemistry behind it all is quite connected. Thiamine is related to some of the most pivotal decisions a cell makes about fuel.

A nutrient sitting at such an important point will naturally show up anywhere the organism is struggling (even marginally) with energy production.

Within the context of my book, The Metabolic Blueprint, we explore the nutrient as one of the key “carb-oxidation spark plugs”. Additionally, it is intimately connected to stress chemistry, lactate, the protective role of carbon dioxide, the danger of impaired oxidative metabolism.

Once you see the thiamine from that perspective, fatigue, brain fog, chaotic appetite, poor exercise tolerance, tissue damage, neurodegeneration, begin to sound like “remixes” of simple impaired cellular energy production.

2. The place where glucose is either finished or stranded

To understand thiamine properly, we need to brush up on some simple high-school biology.

Glycolysis breaks down a glucose molecule into two pyruvate molecules, but it is only the front half of the story. The real energy comes when pyruvate is sent into the mitochondria and converted into acetyl-CoA, where it can drive high-output energy production.

That handoff is extremely important, and thiamine is one of the nutrients that are fundamental for it to happen properly.

The enzyme at the center of that handoff is pyruvate dehydrogenase, a.k.a PDH. It is the gate that decides whether carbohydrate is going to be fully burned or left half-done.

When PDH is running well, a carbohydrate meal can become warmth, steady blood sugar, high energy, motivation and clearer thinking.

If PDH is sluggish (which is the case for many), pyruvate starts piling up without full oxidation. Some of it gets pushed into lactate, and some of it into less favorable side pathways.

The body relies more on fatty acids (which is the default for a more stressed system), and increases adrenaline and cortisol. It feels like heaviness after meals, shakiness, brain fog, irritability, reactive hunger and poor energy.

Then there is transketolase, the third major piece of the thiamine story, and one that helps explain why thiamine shows up as an effective treatment in diabetes, vascular damage, neuropathy and much more.

Transketolase works in the pentose phosphate pathway. Again in practice, it helps the body handle sugar without letting excess spill into harmful chemistry. When sugar is running high and is badly managed, carbon starts crowding into pathways that produce glycation, oxidative stress, inflammatory signaling, and tissue damage.

Benfotiamine became famous largely because it can drive transketolase activity and reroute that overflow into safer pathways. Through this, thiamine becomes much more than simply energy, and even touches on blood, nerves, retinas, and protects against glycation and damage.

With regards to efficient fuel burning, when carbs are properly handled, they not only generate lots of ATP. They also generate carbon dioxide, which sounds negative until you look deeper.

The gas helps stabilize acidity and powerfully opposes some of the harsher conditions that come with excessive lactate. It generates acetyl-CoA, one of the central parts in metabolism, feeding everything from energy production to steroid synthesis. Even through transketolase, it helps sustain glutathione and protects the cell from stress. This is not to mention that extra local CO2 increases oxygen usage in the cell, the recipe for higher efficiency.

A cell that oxidizes well is easier to keep clean. So thiamine affects the burn itself, and it affects the way the cell handles the stress of existence.

Through all of this, thiamine can seem strangely extensive in its effects. It is present where sugar is handled, where energy production is sustained, and allows overflow to be managed properly.

3. The forgotten middle (functional deficiency)

Medicine is comfortable with clear guidelines. A person is deficient or sufficient, sick or fine, normal or abnormal. Real life looks different though. Marginal insufficiencies can still affect daily life, even if not clinically significant.

Beriberi, Wernicke’s encephalopathy, severe alcohol-related depletion, they are obvious thiamine deficiency states. We don’t see them too often.

However, the interesting part is the gray zone in the middle, where someone has enough thiamine to avoid clinical problems but still does not have enough to run high-demand tissues at their best.

Enough to survive, but not enough to thrive.

2013 IBD study

There’s a study on individuals with IBD that illustrates this well.

In 2013, Costantini and Pala gave high-dose oral thiamine (roughly 600 to 1,500 mg a day for 20 days, likely from thiamine HCL) to 12 patients with inflammatory bowel disease and chronic fatigue.

Ten had COMPLETE regression of fatigue. The remaining two improved dramatically. It’s extremely important to note that their baseline blood thiamine values were normal beforehand.

A later randomized placebo-controlled crossover trial in quiescent IBD tried similarly. Four weeks of weight-adjusted high-dose thiamine, roughly 600 to 1,800 mg a day, reduced fatigue far more than placebo

Knowing this, it’s easy to infer that a person may be consuming enough B1 on paper while still struggling with absorption, transport of the nutrient, activating it or simple demand. Disease and stress especially can increase demand. So can inflammation, modern diets and alcohol. “Normal thiamine levels” don’t tell us enough in the context of modern lives.

That forgotten middle is where I see so many modern people living. They are not struggling with deficiency diseases, but they are dragging their feet. Energy doesn’t feel as high as it could be, and life can be bottlenecked.

Fortification and reference ranges made this blind spot worse in my honest opinion. A large population can avoid deficiency and still lose clean oxidative metabolism. Blood can look normal with regards to reference ranges, while tissues stay bottlenecked. The modern person is rarely dying of a single missing nutrient in the old medical textbook way. The modern person is more often running, but halfway

4. Clearer mind, steadier mood, more room inside your own life

In 1997, David Benton and colleagues gave 120 young women either a placebo or 50 mg of thiamine (likely thiamine hydrochloride) every day for two months.

These were not women with extraordinary conditions. No alcoholics, no beriberi.

And yet the group taking thiamine reported feeling more clearheaded, more composed, and more energetic, with faster reaction times.

When the brain is sluggish, life itself becomes narrower and worse (see my high flux article). Everything from decisions to small tasks, become harder and worse. Less patience, less tolerance, easier to derail.

That is part of the larger philosophical background in my book The Metabolic Blueprint – energy changes how much life a person can handle without fear, strain, pain or resistance.

Therefore, seeing such benefits from thiamine, gives us a clue that it can directly improve experienced life.

Studies on Parkinson’s makes this much more dramatic.

Costantini experimented with high-dose thiamine in individuals with Parkinson’s disease. Substantial and sustained improvements in motor and non-motor symptoms were observed, often within months. Earlier reports were significant enough on their own, too.

Parkinson’s is a disease of movement, but it is also a disease of lower initiative, slowing and lower dopamine. Anything that reliably improves that, deserves real attention. Thiamine’s involvement with energy is extremely relevant here.

It’s interesting to note that B1 has been shown to benefit even migraines. A 2024 randomized trial in women with episodic migraine found that 12 weeks of oral thiamine at 990 mg a day reduced migraine disability, frequency, duration, and severity. The brain is one of the most energy-hungry tissues in the body. When its fuel handling becomes unstable, the result does not always reliably feel like fatigue or cognitive decline. Sometimes it’s sensory overload, lower resilience and pain.

A trial on benfotiamine (a form of thiamine) on Alzheimer’s trial adds another layer. People with mild amnesia or mild Alzheimer’s disease took 300 mg twice daily for a year. It lead to less worsening on cognitive measures, significantly less functional decline and preserved glucose metabolism in the brain.

Looking at all of this together, these papers create a picture that thiamine is orbiting around clarity, speed, motor function, and the metabolic conditions under which a brain remains available to itself.

When the cortex has more energy, life feels less cramped and the world becomes more manageable. I’d even argue it increases self-agency, allowing you to handle more of your own life with strength and resilience.

5. Fatigue is a metabolic clue

Fatigue has been normalized for so long that many people no longer recognize how biochemical it can be.

Unfortunately tiredness is treated as laziness, low mood is seen as a problem in and of itself, lack of discipline is a personal failure or a vague modern weakness. I’m not saying it’s purely other factors, but it is often that it’s merely a mental state stemming from a body with impaired energy production.

The IBD studies are clear in this regard. Chronic fatigue in IBD is common, and it often persists even when the bowel disease itself isn’t significant or “active”. The response to high-dose thiamine was so strong that it bordered on unbelievable until the later randomized trial confirmed the findings.

That made fatigue look less like a vague symptom and more of an energetic issue.

Even in fibromyalgia, high-dose thiamine produced dramatic improvements in fatigue and pain in a small case series.

In multiple sclerosis, 14 of 15 patients with fatigue improved on high-dose thiamine.

By themselves, these are not gigantic definitive trials, but the fact that the result keeps showing up matters. Many different conditions, same nutrient, and largely the same direction of change.

This way of looking at fatigue is far more humane. It suggests the possibility that many exhausted people are not weak or mentally defective, but they could simply be underpowered.

It can be trying to run a high-demand organism on compromised foundations.

The body can fake energy for a long time by borrowing from stress hormones, like I explore in the high flux article and my book. Borrowed energy always comes at a price that always gets paid, and it’s often not reminiscent of health.

Fatigue is often the first place a bottleneck announces itself, and shows up often even before a disease is fully formed. It shows up when the organism is compensating yet functioning, outwardly normal but inwardly paying a tax. In that setting, thiamine becomes an insurance for proper energy functioning.

6. Lactate, ammonia, physical capacity

Exercise exposes fuel handling in a way almost nothing else can. A person can hide their energy bottlenecks for a long time when working, doing errands, and general living. But put that same person on a bike, under a barbell, or into a long walk on a hill, the truth comes out quickly.

Either the body is properly turning fuel into movement with grace, or the effort becomes excessively difficult, too quick.

There was a trial done in nine trained female university athletes.

Over a four-week thiamine phase using TTFD (my personal favorite form of thiamine), dosed by bodyweight at roughly 10 mg/kg (a high dose), the women rode a bicycle at 70% of maximal oxygen uptake for an hour.

During that effort, lactate fell, ammonia fell, and the rating of perceived exertion fell across the session. The authors described a shift that resembled endurance training in the way carbohydrate metabolism improved. That is remarkable.

This matters even though it was in a training setting. Lactate is what unfinished carbohydrate metabolism produces like when the rate of demand is higher than clean oxidation. Ammonia is another sign that the system is paying a price for the work being done. Lowering those burdens completely changes how exercise feels, positively.

A striking study on mice given TTFD gave similar results.

After four weeks of supplementation, swimming time until exhaustion rose by 5.4x, 6.4x, and 7.6x across the three dose groups (increasing dosages).

Grip strength improved too, but the focus was in the chemistry around the performance. Again, post-exercise lactate was lower, lactate production fell, blood urea nitrogen and creatine kinase were lower after exertion, and glycogen stores in both liver and muscle were higher.

The animals were better supplied, less stressed by effort, and less biochemically exhausted by the work.

I want to make the claim that the benefits of thiamine reach beyond sport, and that sports were just one clear way of seeing the benefits.

Physical capacity is one of the easiest outward expressions of metabolic coherence. A body that stores fuel well, burns it well, and leaves less wreckage behind will feel different in the gym AND in real life. On a run, during sex, while carrying groceries, while going up stairs, while living.

7. Why TTFD is my preferred source

If you’ve been in the health space, you’ve probably heard people talking about taking TTFD. They talk about it helping them move through life, about it increasing motivation and reducing internal drag. It’s easy to dismiss these claims as supplement culture is full of marketers, peddlers and misinformation. The literature, though, gives TTFD a proper case.

In a 2018 Scientific Reports paper, TTFD increased voluntary locomotor activity in rats in a normal cage and increased voluntary wheel running in a dose-dependent manner. Consistent with higher willingness to do things, and higher motivation. The extra movement was synchronized with dopamine release.

When the researchers blocked the dopamine D1 receptor in that region, the TTFD effect disappeared. That’s an extremely powerful clue. The supplement influenced drive, activation, and goal-directed behavior.

The same paper explains why TTFD may feel different from plain thiamine. TTFD is absorbed rapidly and metabolized. The metabolized thiamine interacts with dopamine.

Therefore, stories (even my personal experience) of effort costing less than before, has a real reason behind it. The brain is no longer dragging itself through every act of initiation. Starting, deciding, moving, and following through are actions built out of energy.

8. The different forms of thiamine

Plain thiamine hydrochloride has the longest history. It is cheap and perfectly capable of increasing cellular levels. It’s water-soluble and higher intakes can saturate, but it has real history in literature and clear benefits.

TTFD is the form people tend to feel more directly. It is fat-soluble and absorbed extremely well. The literature around TTFD gives it a real place in exercise tolerance, voluntary activity, dopamine, and mental and physical willingness. It is the form that keeps showing up with regards to movement, initiative with a cleaner sense of drive.

Benfotiamine shines in the context of excess glucose with special regards to diabetes. It feels less like a “motivation” form and more like a tissue-protection form, though that understates it. What benfotiamine does especially well is change where glucose goes when a high-sugar environment would otherwise turn corrosive. Helps glycation, raises thiamine levels, and again, improves energy production.

Then there are sulbutiamine and prosultiamine, which complicate the story a little further. With regards to forms of thiamine, one form may enter certain tissues more readily, another may generate the active coenzyme forms more effectively, another may behave beautifully in one context and worse in another.

Merely claiming that “thiamine worked” is often too blunt of a claim. Sometimes thiamine HCL worked. Sometimes TTFD worked, sometimes benfotiamine was the right tool for the job.

The form changes the experience, the pharmacology, and sometimes the whole result.

For general lifestyle benefits, I greatly prefer TTFD.

9. Benfotiamine and excess glucose

To reiterate, TTFD shines when the goal is better effort, initiative, endurance, and felt energy. Benfotiamine is incredible to protect the tissues from damage.

The Hammes paper remains one of the most important studies in this context.

In diabetes, several destructive pathways appear when upstream metabolites pile up. Benfotiamine activated transketolase and pushed those metabolites into safer handling through the pentose phosphate pathway.

In doing so, it suppressed AGE formation (glycation damage) and many other harmful things. In diabetic eyes, that shift was so strong that retinal problems were prevented.

When glucose flux rises, the question becomes where all that carbon is going. It can either go towards oxidation (which is preferred for health), toward storage, toward repair or toward damage. Benfotiamine alters the traffic beneficially.

Shahmiri and colleagues had a study in twelve people with impaired glucose tolerance or newly diagnosed diabetes.

They gave them 300 mg a day of benfotiamine for six weeks and improved glucose tolerance. During the placebo period, fasting glucose, fasting insulin, and insulin sensitivity deteriorated. During the thiamine phase, they did not.

A nephropathy paper showed that in forty people with type 2 diabetes and microalbuminuria, high-dose thiamine at 300 mg a day for three months lowered urinary albumin excretion, and about a third of the treated patients returned to normal albumin levels. This shows improved kidney health.

Energy is half of the story surrounding thiamine, certainly, but protection is the other half. Retina, kidney, nerve, vessel walls… these are all places where excess glucose can do slow and really expensive damage. Benfotiamine is truly powerful in protecting from this excess cellular glucose damage.

(let me be clear that it’s improper sugar handling, not sugar as the problem in and of itself. I’m heavily pro-carbohydrate in my works, articles and books)

10. The liver

Through the lens of my book The Metabolic Blueprint, the liver matters immensely for thyroid function and lived energy.

The liver is one of the main places where T4 is converted into active thyroid hormone (T3). A less fatty, more oxidative liver is more capable of supporting warmth, energy, and the higher-output endocrine state people recognize as feeling alive. Better energy, better hormones, more life.

In a study done on sheep, researchers overfed sheep on a high-calorie, carbohydrate-rich diet to develop hyperglycemia, hyperinsulinemia, insulin resistance, and fatty liver. Then they added thiamine.

The treated animals ended up with completely normal levels of liver fat despite eating the same liver-fattening diet. The liver’s capacity for carbohydrate and fat-burning rose as well. The high-calorie diet had created a low liver-thiamine state, and taking thiamine reversed it.

The diet didn’t change. Taking thiamine changed how the diet was received in the system.

A fatty liver is a whole-body problem. It handles glucose poorly, stores and exports fat badly, sends distorted signals into the rest of the organism, and becomes a huge drag on everything downstream.

A liver that stays glycogen-replete, keeps burning well, and resists fat accumulation is an extremely powerful organ.

Earlier rodent studies showed similar results. Thiamine keeps pushing an overfed organism away from clogged storage and toward active combustion.

The liver decides whether abundance turns into usable life or into a traffic jam and obesity. Focusing on liver health is crucial for quality of life, and thiamine keeps showing that it’s strongly protective.

11. Digestion

A person can have good health elsewhere, but if their digestion is impaired, it has consequences that impact virtually everything (even their mindset, through serotonin. I explore this in my book).

The gut is full of high-demand tissue. It has smooth muscle that has to move rhythmically, nerves that have to signal properly, secretory cells that have to release acid and enzymes at the right moment, and a powerful barrier that has to stay intact while meeting different things from the outside world all the time.

Thiamine deficiency has been linked to impaired digestion at almost every level.

A gut that cannot make energy properly does not contract properly. A gut with impaired signaling does not coordinate itself properly. A gut with weak secretion does not prepare food properly.

Slow motility becomes constipation, nausea, bacterial overgrowth, and general dysfunction. Weak gastric acidity means poorer protein breakdown and weaker mineral release upstream. Poor pancreatic output means protein, fat, and carbohydrate are left more partially digested downstream. Barrier problems open the door to irritation, whole-body inflammation which has huge negative effects. A person ends up living in a miserable state in this case.

Thiamine insufficiency can start as a gut problem, linger as a gut problem, and be mistaken for a gut problem until thiamine is addressed.

Thiamine changes the entire digestive story. Meals feel less hostile, bloating weakens, appetite becomes cleaner, and digestion gets quieter in the most boring but beneficial way possible.

12. Warburg and cancer metabolism

Between 1923 and 1924, Otto Warburg observed that cancer cells are characteristic in that they anaerobically ferment glucose to lactate even in the presence of oxygen.

Modern cancer biology has made the picture more complicated than Warburg first had observed, but the broader picture is still there. There’s high glucose burning but excess lactate, and a cell that is not handling fuel oxidatively.

Through PDH, thiamine becomes relevant here. Cancer cells often suppress PDH (by phosphorylation through pyruvate dehydrogenase kinases), and pyruvate has a harder time becoming acetyl-CoA, and carbon is left crowding outside the Krebs cycle.

More glucose is consumed, more lactate is produced, more of the cell’s fuel handling shifts toward rapid glycolytic throughput and away from full oxidation.

A 2014 high-dose thiamine study showed that in two cancer cell lines, high-dose thiamine reduced PDH phosphorylation, lowered glucose consumption, lowered lactate production, and suppressed cancer proliferation.

Whenever pyruvate is kept outside of oxidative metabolism, the organism starts living with rougher chemistry, and it can resemble cancer in many ways. In cancer, the chemistry is obviously far more extreme, but the underlying logic is recognizable.

In a 2020 paper that looked at thiamine mimetics, both sulbutiamine and benfotiamine increased the anti-cancer effect of thiamine in vitro, increased intracellular thiamine and TPP, and reduced PDH phosphorylation.

In another model, benfotiamine reduced tumor growth while sulbutiamine did not, but the authors themselves concluded that TPP from thiamine appeared to be the active species mediating the inhibitory effect on cancer growth.

All of this is interesting as it reveals a deep resemblance between cancer metabolism and the weaker, more ordinary forms of unfinished energy that run through modern life. Cancer is obviously not the same thing as post-meal fog, poor exercise tolerance or a bad response to carbs. However, it overlaps in its metabolic clues: suppressed oxidative metabolism, excess lactate, heavy reliance on glycolytic throughput, and a cell that has lost contact with the cleaner chemistry of full respiration. Thiamine sits intimately with all of these.

13. The question of what is “natural”

I’m writing this section for many of my readers that have discarded any and all discussion surrounding supplements, because they aren’t “natural”.

The word “natural” has too much authority in these spheres, honestly. It ends arguments before the real physiology has even been examined. A person feels awful on carbs, takes thiamine, starts feeling significantly better, and someone declares that this proves carbohydrate was never appropriate in the first place.

That conclusion is far too hasty and honestly uninformed. The body requires cofactors for everything.

It requires machinery for fat oxidation, for protein handling, for vision, for thyroid function, for oxygen use, for every serious act of life.

The need for machinery to burn fuel does not discredit the fuel itself!

Modern life is also exceptionally good at damaging the conditions under which carbohydrate is oxidized well.

Chronic stress pushes up free fatty acids. Long low-carb diets teach the system to downregulate glucose oxidation. Alcohol drains thiamine, gut dysfunction disturbs absorption, hyperglycemia increases overflow stress. Ultra-processed foods raise throughput while lowering necessary cofactors.

14. What comes back when energy is no longer borrowed

When the brain is running on low throughput, life gets smaller. Decisions become hard, life feels overly complicated, everything feels heavier, and you need more urgency and stress to get things done. The whole day acquires a faint feeling of drag. That is a metabolic problem. Benton’s study on women, the Parkinson’s studies, the TTFD dopamine data, the fatigue studies — all of them touch different parts of that same problem.

When energy stops being borrowed, willingness is often the first thing to return. The body feels less defensive. Effort no longer needs a high price. Thinking becomes more free. More steadiness in the hands, the voice, the stomach, the walk, the afternoon, life.

The exercise studies show it from the muscular side, the gut studies show it from the digestive side, the liver studies show it from the endocrine side, the dopamine studies show it from an initiative and willingness side.

Put all of that together and we get a large picture.

A more oxidative organism is easier to live in, and thrives more than merely surviving.

The pace at which a person can think, choose, eat, train, recover, and stay emotionally well is the living expression of metabolism.

15. A speculative extension

The big idea is that a great deal of people may be living in a shallow shortage of thiamine without ever touching true deficiency. They get through life well enough to pass, but bottlenecked.

One practical detail – sometimes thiamine is the main bottleneck, sometimes it is only the first one. I’ve had many readers explain to me that taking thiamine has caused them headaches and other problems.

I believe the following: once glucose starts moving forward more cleanly, other weak links can become easier to notice, ESPECIALLY magnesium and potassium.

Magnesium sits inside ATP itself as Mg-ATP, so a system trying to raise energy without enough magnesium can feel twitchy, crampy, or incomplete. Potassium matters more as carbohydrate intake rises because insulin helps move potassium into cells. If potassium intake is marginal, better carbohydrate handling can expose that potassium shortage as fatigue, flatness and other problems.

Know that a VAST majority of adults are having too little potassium and magnesium. It is a very common insufficiency, so look into it.

This is a good argument for keeping magnesium replete and having enough potassium.

16. The ending

Thiamine keeps showing up in places that look unrelated until the shared denominator comes into view.

Fatigue. Mood. Cognition. Exercise. Lactate. Digestion. Diabetes. Fatty liver. Parkinson’s disease. Alzheimer’s disease. Even parts of the Warburg problem and cancer metabolism.

Thiamine sits uniquely close to where food becomes useful life.

The Metabolic Blueprint

The Metabolic Blueprint is the result of years of studies, health research, analysis and trial & error. The all-in-one guide for reclaiming your youthful health & energy.

As a token of gratitude, here’s a code for 20% off of The Metabolic Blueprint:

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