Protocols for addressing thiamine deficiency &

the paradoxical reaction

Elliot Overton DipCNM, CFMP

Copyright © 2022 Elliot Overton 1

 Medical disclaimer

The information provided by Elliot Overton (EONutrition) contained within this informational
booklet is for general information and educational purposes only and is not medical advice.
Elliot Overton is not a medical professional. You should consult your physician or your health
care provider if you are seeking, medical advice, diagnoses, or treatment. Never ignore
professional medical advice based on anything contained herein.

Under no circumstance shall Elliot Overton be responsible or liable for any damages arising out
of or in connection with the use of this informational booklet. This includes (without limitation)
compensatory; direct, indirect, or consequential damages and general damages.

Your use of this informational booklet produced by Elliot Overton, and the reliance on any
content is solely at your own risk. Use of this informational booklet implies your acceptance of
this disclaimer.

All information is provided in good faith, however Elliot Overton makes no representation of
warranty, express or implied, regarding accuracy, validity, reliability or completeness of any
information.

The statements made within this informational booklet have not been evaluated by the U.S.
Food and Drug Administration, European Medicines Agency (EMA) or the The Medicines and
Healthcare products Regulatory Agency (MHRA).

Copyright © 2022 Elliot Overton

No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, without
prior written permission from EONutrition, except in the case of brief quotations embodied in reviews and certain
other non-commercial uses permitted by copyright law.

Copyright © 2022 Elliot Overton 2

 Table of Contents
Introduction 2
Systems supported by thiamine & biochemical functions 2
Functional and regional deficiency 5
Causes of thiamine insufficiency 6
Different forms of thiamine supplements 7
Thiamine salts 7
Thiamine pyrophosphate 8
Benfotiamine 9
Thiamine tetrahydrofurfuryl disulfide (TTFD) 10
Sulbutiamine 11
Dosage equivalence 12
What is a mega dose? 13
The paradoxical reaction 14
Mitigating the symptoms 15
A basic thiamine protocol 17
Choosing the right form of thiamine 18
Thiamine protocols, introduction and disclaimer 19
Objective Nutrients Mega Dose Protocol 21
Generic Thiamine Mega Dose Protocol 25
Objective Nutrients Sensitive Protocol 29
Generic Sensitive Protocol 34
Important protocol information 39
Protocols for thiamine-responsive health conditions 40
Gastrointestinal conditions 41
IBS & Small intestinal bacterial overgrowth (SIBO) 41
Hypochlorhydria, GERD or gastroparesis 43
Cholestasis, liver or gallbladder insufficiency 45
Intestinal permeability 47
Neurological conditions 49
Neuropathy and nerve pain 49
Brain-fog, lack of concentration or mild cognitive impairment 51

Copyright © 2022 Elliot Overton 3

 Multiple sclerosis 53
Parkinson’s Disease 55
Postural orthostatic tachycardia syndrome 57
Generalized neuroinflammation of any cause 59
Cardiometabolic conditions 61
Heart failure and angina 61
Hypertension 63
Diabetes Mellitus (type II) 65
Other health conditions 67
Fibromyalgia 67
Chronic fatigue syndrome / ME 69
Interstitial cystitis 71
Pre-menstrual syndrome 73
Identifying nutritional imbalances through testing and symptoms 75
Thiamine 76
Magnesium 78
Sodium 79
Potassium 80
Riboflavin (vitamin B2) 81
Niacin (vitamin B3) 82
Pantothenic acid (vitamin B5) 83
Pyridoxine (vitamin B6) 84
Biotin (vitamin B7) 85
Folate (vitamin B9) and Cobalamin (vitamin B12) 86
Choline 88
Molybdenum 89
Lipoic acid 90
Glutathione 91
Test interpretation for bloodwork (CBC, CMP, other markers) 93
Test interpretation for urine organic acids 96

Copyright © 2022 Elliot Overton 4

1. Introduction to thiamine deficiency and
the paradoxical reaction

Copyright © 2022 Elliot Overton 1

 Introduction

What is thiamine?
Thiamine is a water-soluble B vitamin (vitamin B1) found in varying amounts in a wide
variety of foods. Thiamine is best known for its role in breaking down carbohydrates for
energy, and the demand for thiamine increases with higher intake of carbohydrates.

Thiamine also participates in the utilization of certain amino acid and fatty acids, as well as
playing central roles in the function of nerve cells in the brain and throughout the
periphery. To be used inside the cell, thiamine must be activated into thiamine
pyrophosphate (TPP).

Main systems supported by thiamine

Although low levels can affect every cell and therefore every organ, a deficiency usually
produces symptoms manifesting in four main areas of the body. These systems include the
central and peripheral nervous system, the heart and circulation, and the digestive system.

Copyright © 2022 Elliot Overton 2

Coenzyme function
Like other vitamins and minerals, active thiamine serves as a cofactor/coenzyme or
“helper” for enzymes. Enzymes are used by our cells to increase the rate of chemical
reactions. This often includes converting one molecule into a different molecule, as shown
below:

Enzymes which need thiamine

Some of the enzymes which require thiamine are involved in the generation of cellular
energy from the breakdown of fats, carbohydrates, and proteins. Another is involved in
building other molecules and improving our antioxidant defence system. Without thiamine,
the rate of these enzymes slows down.

Copyright © 2022 Elliot Overton 3

The “gateway” to energy metabolism
Thiamine has been described by Dr Lonsdale and Dr Chandler Marrs as sitting at the
“gateway to energy metabolism”. This is because two of the enzymes which need this
vitamin are considered “rate-limiting”. If they slow down, then every following step of
energy metabolism also slows down and the cells run up an energy deficit. This makes
thiamine extremely important for continual production of energy

Non-coenzyme effects

Thiamine also exists in two other main forms in the cell called thiamine monophosphate
(TMP) and thiamine triphosphate (TTP). Although some functions of these forms have
been established, much is still unknown. It is postulated by many researchers that these
forms possess non-coenzyme effects. This can include direct actions on different cell
components, genetic effects, and communication with other cells.

Furthermore, several non-coenzyme effects of thiamine pyrophosphate have been

identified. These include:

• Regulation of other enzymes involved in neurotransmitter synthesis and

breakdown, and energy metabolism
• Antioxidant, anti-inflammatory, and effects on gene expression

Copyright © 2022 Elliot Overton 4

“Functional deficiency”
More recent evidence shows that regional deficiency can occur in different organs due to
non-classical risk factors. For example, oxidative stress, and inflammation can cause
destruction of the thiamine molecule.

Alternatively, these factors may inhibit or “block” the enzymes which use thiamine. This
leads to the equivalent of a deficiency, and may be present only in specific regions, tissues,
or cells. This can be described as a functional deficiency.

Regional deficiency and dependence

Regional functional deficiencies have been identified in different areas of the brain, as
well as the heart and some other organs, and can occur even when there is enough
thiamine in the diet. For this reason, ordinary testing methods (as described below)
can yield inaccurate results and relying on dietary sources of thiamine is not sufficient
to address the underlying problem.

For this reason, many chronic health conditions may be responsive to thiamine
supplementation despite someone not displaying any of the typical risk-factors for
deficiency.

In the case of chronic regional deficiencies, high doses on a consistent basis are often
required to restore cell energy metabolism. Furthermore, if the underlying cause of
the functional deficiency (inflammation, infection, toxicity, oxidative stress) is not
addressed, someone may become “dependent” on thiamine to feel symptomatically
normal, and relapse when they discontinue.

Copyright © 2022 Elliot Overton 5

Potential causes of thiamine insufficiency
Insufficiency of this nutrient is likely to be much more widespread than is conventionally
believed. With the advent of processed foods providing empty calories which have been
stripped of micronutrients, insufficiency of essential vitamins and minerals is not a rare
finding. The excessive consumption of refined carbohydrates, so common across the
world, is known to deplete thiamine.

However, a host of other factors have also been implicated in the development of thiamine
insufficiency. The main causes have been listed below:

Different forms of thiamine

The next section looks at all the commercially available forms of thiamine, including the
synthetic thiamine derivatives. The pros and cons of each form is examined, along with
how each form is processed within the human body.

Copyright © 2022 Elliot Overton 6

Thiamine Hydrochloride & Mononitrate
Both forms fall under the category of thiamine salts. They are made up of one thiamine
molecule bound with either nitrate or hydrochloride. They are the most readily available and
widely used forms of thiamine, along with being the cheapest. Some people report good
benefits from using either form, but the dose required to achieve effects is generally much
higher compared with thiamine derivatives.

Benefits & drawbacks

Pros
• Can be purchased in pure
• Cheap and widely available • Low side effect profile
powder form

• Can be dosed in very high • Useful for sensitive

• No added sulfur content
amounts individuals

Cons

• Dependent on cellular
• Poor absorption at low doses • Poor brain penetration
transporters

• Less effective at
• Very high levels needed for • Requires transporters into
increasing active thiamine
passive diffusion the brain
in cell

Copyright © 2022 Elliot Overton 7

 Thiamine Pyrophosphate
Thiamine pyrophosphate is the active form of thiamine which is used inside the cell.
Unfortunately, when it reaches the intestine it becomes converted back into normal
thiamine before absorption into the blood. That said, some individuals report superior
benefits from using sublingual lozenges (which may be absorbed via that route instead).

Benefits & drawbacks

Pros
• May have superior effects to
• Low side effect profile • Positive anecdotal reports
thiamine salts
• No additional sulfur
• If absorbed, may help with • Useful when used
groups for sensitive
activation issues intravenously
individuals

Cons
• In practice, less effective
• Poor gut absorption for the central nervous • Understudied and less used
system
• Similar absorption rate to
• More expensive than thiamine • Rate of absorption via
thiamine from thiamine
salts buccal cavity is unknown
salts

Copyright © 2022 Elliot Overton 8

 Benfotiamine
Benfotiamine is a synthetic s-acyl derivative of thiamine which has high bioavailability
and is readily absorbed into the blood. It has been heavily studied for its benefits in
addressing neuropathy and other diabetic complications and shows promise for
Alzheimer’s dementia. It can rapidly improve organ levels of thiamine and is free of any
additional sulfur compounds.

Benefits & drawbacks

Pros

• Widely available • High bioavailability • Non-coenzyme effects

• One of the most studied • Can increase brain levels • Antioxidant and anti-
thiamine derivatives in long-term studies inflammatory activity

Cons
• In practice, less effective
• Can induce a more severe
• S-benzoylthiamine is unstable for the central nervous
paradoxical effect
system
• Can be rapidly metabolized to • Most research is • Potent for novices who are
normal thiamine in liver published in Japanese not accustomed to thiamine

Copyright © 2022 Elliot Overton 9

 TTFD
(thiamine tetrahydrofurfuryl disulfide)
TTFD contains one thiamine molecule bound with a sulfur group by a disulfide bond.
This extra group allows thiamine to enter cells freely, bypassing all transport systems.
Once inside the cell, the thiamine is released and “trapped” inside yielding high levels.
This form has been heavily studied in Japan since the 1960s but is not well known in the
Western world.

Benefits & drawbacks

Pros
• Direct action on digestive
• Rapidly enters brain • High bioavailability
system

• Rapidly taken up by • Useful for central nervous • Antioxidant & mild chelating
enteric nerves system conditions effects due to sulfur group

Cons

• Sulfur can cause reactions a • Can induce a more severe

• Not widely available
minority paradoxical effect

• Less is known compared • Most research is published in • Potent for novices who are
with benfotiamine Japanese not accustomed to thiamine

Copyright © 2022 Elliot Overton 10

 Sulbutiamine
Sulbutiamine is another synthetic disulfide derivative made up of two thiamine molecules
bound together by a disulfide bond. This form processed inside the cell in a similar way to
TTFD and exerts similar actions. Most of the research on sulbutiamine has been relating to
brain function, enhancing dopamine release, and relieving fatigue.

Benefits & drawbacks

Pros

• Rapidly enters brain • High bioavailability • Quite well studied

• Dopamine enhancing • Useful for central nervous • More research published in

effect system conditions English compared with TTFD

Cons

• Not widely available (e.g., • Sulfur can cause reactions a • Can induce a more severe
on Amazon) minority paradoxical effect

• Less is known compared • Anecdotal reports suggest • Potent for novices who are
with benfotiamine less effective with time not accustomed to thiamine

Copyright © 2022 Elliot Overton 11

Is there dosage-equivalence between forms?
One of the most frequent questions I am asked is how to know
the difference in dosage between the different derivatives of
thiamine. For example, if someone regularly take 600mg of
benfotiamine but wants to switch to TTFD or sulbutiamine,
then how much of that form should they take instead (what
would be the dose equivalent)?

The problem is that no one knows the answer to this question.

Based on bioequivalence studies, benfotiamine and TTFD (and
probably sulbutiamine) have similar bioavailability (absorption
via the gut). That should mean that benfotiamine and TTFD
can be dosed at a similar level to one another.

Compared with thiamine hydrochloride, the estimated increase in bioavailability is

between 5-10 times greater. Thiamine HCL is thought to be absorbed at a rate of 5-
10%, whereas some studies have shown beyond 90% absorption for benfotiamine and
TTFD.

However, these two forms are processed by the body and increase thiamine
metabolites in a different way. Furthermore, the breakdown products of the different
forms exert different effects on the cell.

This means that they are not equivalent in their action, and it could therefore be
unproductive to compare them to each other. They are simply different, with one form
working better for some people and the other form working for others. From a clinical
perspective, I have found that lower doses of TTFD are needed to achieve similar
effects to higher dosages of benfotiamine. However, this is not an exact science and
merely anecdote at this point.

To make things even more confusing, thiamine hydrochloride can initiate passive
diffusion through the intestine when taken in a high enough dose (the dose is unknown,
but I can speculate that it is between 500-1000mg). This means that it can bypass
transporters and be absorbed at a much higher level than if it is taken in a lower dose.

This means that we cannot accurately determine what the equivalent doses of TTFD,
benfotiamine, or thiamine hydrochloride are if mega doses are consumed. The
unfortunate fact is that mega doses of thiamine hydrochloride are sometimes
completely ineffective for some people, even when extremely high. Those people often
notice immediate and substantial changes if they switch to using TTFD or
benfotiamine.

To conclude, the only way to know how to proceed with dosing is to try different forms
at different doses and assess how symptoms respond.

Copyright © 2022 Elliot Overton 12

How much thiamine is a “mega dose”?
Another topic I am frequently asked about is how much thiamine is classed as a “mega
dose” or a “high dose”.

To put it simply, there is no correct or exact definition of these terms.

The recommended dietary allowance ranges from 1-1.5mg per day obtained from food.
One could therefore argue that a “high dose” could be defined as 100x, or even 10x that
amount.

Several years of clinical experience working with countless individuals using thiamine in
different forms and doses, coupled with the feedback I regularly receive from many
people across the world, has led me to conclude that a “mega dose” is much higher than
100x the RDA. This is supported by numerous studies which have used much greater
doses.

To be more precise, when I use the term “mega dose”, I am referring to the EFFECTIVE
dose. The effective dose differs from person to person and depends on the form used.
Based on what I have learned and witnessed, below is an estimation of the effective
doses for the different forms.

Effective dose for different forms:

Note: sulbutiamine is likely equivalent to TTFD, but I do not have much clinical
experience with it.

Copyright © 2022 Elliot Overton 13

 The Paradoxical Reaction

Quick definition
• People who begin supplementing with thiamine often notice a temporary worsening of
symptoms. They get “worse before they get better”

• This is most pronounced in people who are severely deficient

• The symptoms which worsen are usually the ones originally associated with thiamine
deficiency

• The paradoxical reaction can be mitigated or improved through supplementation with

other supporting vitamins and minerals

What is the paradoxical reaction?

One of the pioneers of high-dose thiamine as a medical treatment, Dr Derrick Lonsdale,
coined the term “paradoxical reaction” to describe the temporary worsening of symptoms
which some people experience when addressing thiamine deficiency. The paradox exists in
the fact that an individual can feel worse, not better, from consuming more of what their
body requires to restore health. This effect has been known ever since the discovery of
thiamine in the early to mid-20thcentury and was documented by doctors throughout both
the West and the East.

These symptoms are often most pronounced in individuals who have long-term or severe
deficiencies and can generally last for anywhere between a few days and several weeks.

There are a few theories for why the paradoxical reaction may occur. Lonsdale suggests that
the addition of thiamine facilitates the body’s shift moving out of a state of metabolic
catabolism (tissue breakdown, stress response) towards anabolism (tissue building, resting
state). The process can be tiresome for the body and requires an adaptation period.

Whilst I believe this to be possible, I personally believe that the paradoxical reaction is more
related to an increased demand for other nutrients. Experience has shown that many of the
symptoms can be mitigated or completely avoided through supplying the correct nutritional
cofactors.

Copyright © 2022 Elliot Overton 14

 Paradoxical reaction
Symptom improvement

Time

Symptom baseline Symptoms

In the above diagram, the overall collection of symptoms that someone has because of
thiamine deficiency is referred to as the “symptom baseline” (light blue line). At the start of
supplementation with thiamine, some of symptoms can become temporarily worse (the red
line).

During this time, it is advised that someone does not increase their dosage until they have
returned to “baseline” again. This can sometimes take a few weeks for people who are very
sensitive to supplementation. Once an individual returns to baseline, they can incrementally
increase the dose once more.

Common paradoxical reaction symptoms

• Fatigue, lethargy, or muscle
• Anxiety, worry or restlessness
weakness

• Frequent urination or thirst • Insomnia or excess sleepiness

• Nerve pain, tingling or • Reflux, bloating or stomach

numbness acidity
• Headache, brainfog or poor • Altered heart rate, high or low
concentration blood pressure

Copyright © 2022 Elliot Overton 15

 Symptoms with increasing dosage
Symptom improvement

Time

The dose of thiamine should only be increased after symptoms return to baseline. With
each increase in dosage, this will cause a temporary worsening in symptoms once again. As
someone’s body gradually becomes accustomed to using higher doses, this process of
symptom-worsening subsides over time.

Mitigating the symptoms

In many cases, the paradoxical reaction or associated symptoms/side effects from thiamine
supplementation stem from other nutritional insufficiencies. Thiamine may be increasing the
demand for other synergistic nutrients.

Part two of this document specifically deals with many of the common nutrient interactions,
symptoms, and side effects. For a detailed explanation of how to identify symptoms and test
results which highlight increased demand for other nutrients, please refer to section 3.

Copyright © 2022 Elliot Overton 16

Nutritional interactions
The direct and indirect interactions between thiamine and other dietary nutrients is
illustrated in the following diagram:

A basic thiamine protocol

Based on the likelihood of increased nutritional demand during thiamine repletion, the
absolute minimum protocol should at least fulfil the four criteria shown below:

Copyright © 2022 Elliot Overton 17

 Choosing the right form of thiamine

Key points for beginners

• There is no “correct” form of thiamine to supplement. It is entirely individual and needs to

be assessed on an individual basis.

• The best form is based on individual needs & tolerance. Tolerance for different forms can
also change over time.

• Each form has benefits and drawbacks.

• The best way to find the optimal form for an individual is to experiment.

Intolerance to one form will often manifest in unpleasant symptoms. However, it should
be recognised that this can be a normal part of the “paradoxical reaction” and often
subsides with time. The best strategy is to choose and form and utilize the “go low and
slow” approach with dosing. Furthermore, ensuring intake of all supporting nutritional
cofactors (more info in Part 2) can help to mitigate the paradoxical reaction.

It is important to recognise that thiamine derivatives possess greater bioavailability and

can exert a more “potent” effect. This means that the paradoxical reaction can be more
intense for beginners. For this reason, the sensitive protocols listed below always begin
with using small amounts of thiamine hydrochloride, which is generally less potent and can
be better tolerated.

Some people find that this is the best form to take long-term because of negative side
effects from the derivatives. However, many others (perhaps most) discover much greater
benefits from eventually switching to the thiamine derivatives and using these forms long
term.

With the more bioavailable forms, especially TTFD and sulbutiamine, but also
benfotiamine, unpleasant symptoms can usually be traced back to underlying nutritional
imbalances in the other vitamins or minerals. Pinpointing these and addressing them can
improve tolerance for therapeutic doses of thiamine.

If someone experiments with one of the thiamine derivatives and cannot achieve
tolerance, it is advised to stick with thiamine hydrochloride or mononitrate.

Copyright © 2022 Elliot Overton 18

 Protocol information &
disclaimer

Objective Nutrients Protocols

Two of the following thiamine protocols below were formulated by me to provide all
(or most) of the nutritional cofactors and support the process of thiamine repletion. All
products (aside from standalone thiamine HCL powder) can be found on Objective
Nutrients website.

Generic Protocols
Two of the following thiamine protocols below are classified as “generic”, meaning
that any brand of supplement can be used. I have refrained from using product names,
but instead refer to the generic form (such as benfotiamine, TTFD, B complex etc).

I have not included thiamine mononitrate or thiamine pyrophosphate in any of the

protocols because I have not found them to be useful clinically. However, if these
forms provide benefit, then it is advised to continue with doing what works for each
person.

Furthermore, it is important to add that these protocols are examples and can be
customized however one wishes to do so.

Disclaimer (conflict of interest)

I (Elliot Overton)am a cofounder of Objective Nutrients, a company focused on
manufacturing thiamine-related nutraceuticals free of additional fillers or excipients.
Thiamax (TTFD), ThiaMega, Thiavite, ThiActive-B and ThiAssist are products which
were formulated by me to provide nutritional cofactors in the suitable ratios to
support thiamine supplementation.

Other brands/formulations will also suffice if choosing replacement products,

although I do not provide any specific advice with regards to which brands. It is up to
each person to find a suitable replacement product which is tolerated.

Copyright © 2022 Elliot Overton 19

2. Protocols for addressing thiamine
deficiency & mega-dosing

Copyright © 2022 Elliot Overton 20

 Objective Nutrients Megadose
Protocol

Who is this protocol for?

• People with chronic health conditions which may be responsive to high doses of thiamine,
who might have tried a lower dose of thiamine derivative supplements and tolerated them
well.

• Applicable conditions may include: Thiamine deficiency, Neurodegeneration, Parkinson’s,

Multiple Sclerosis, Huntington’s, Postural Orthostatic Tachycardia Syndrome, Chronic
Fatigue Syndrome, Fibromyalgia, Inflammatory Bowel Disease

Protocol key points

• These are example doses only and can be modified based on individual tolerance. Some people
may need to increase at much slower rates than stated below

• Maximum benefits may be achieved at lower doses than shown below. Example: If 1000mg
provides benefit, but 1500mg leads to side effects, return to 1000mg (the optimal dose for that
person).
• Thiamine supplements can be taken at any time of day. However, it is advised to spread the
doses between AM, noon and PM in equal parts.

Mega Dose Protocol Package

ThiaMega multi-form B1 complex

Thiamax (TTFD)

ThiActive B or Thiavite

ThiAssist mineral complex

Copyright © 2022 Elliot Overton 21

Stage 1 (approx. days 0-7)
• The starting dose of thiamine for this protocol is 465mg. The concept is to gradually
build up the dose each week. If 465mg is tolerated, move onto stage 2

Supplement Breakfast Noon Evening Extra info

ThiaMega 1 capsule

Taken with
ThiAssist 1 scoop 1 scoop
food

ThiActive B 1 capsule

Thiamax

Stage 2 (approx. day 7+)

• Increase the dose of ThiActive B and eventually 1 cap Thiamax
• After achieving this the total dose of thiamine is approximately 630mgper day

Supplement Breakfast Noon Evening Extra info

ThiaMega 1 capsule

Taken with
ThiAssist 1 scoop 1 scoop
food

ThiActive B 2 capsules

Thiamax 1 capsule

Copyright © 2022 Elliot Overton 22

Stage 3 (approx. day 14+)
• Gradually add in one more capsule of ThiaMega (you may need to do this over the
space of a few days) and one more capsule of Thiamax
• The dose of thiamine for this stage is approximately 1130mg per day

Supplement Breakfast Noon Evening Extra info

ThiaMega 1 capsule 1 capsule

Taken with
ThiAssist 1 scoop 1 scoop
food

ThiActive B 2 capsules

Thiamax 1 capsule 1 capsule

Stage 4 (approx. day 21+)

• Increase the dose of ThiaMega to three capsules per day, along with three capsules
of Thiamax.
• This brings the dose of thiamine to 1630mg per day

Supplement Breakfast Noon Afternoon Extra info

ThiaMega 1 capsule 1 capsule 1 capsule

Taken with
ThiAssist 1 scoop 1 scoop
food

ThiActive B 2 capsules

Thiamax 1 capsule 1 capsule 1 capsule

Copyright © 2022 Elliot Overton 23

 Stage 5 (day 30+)
At least one full week at 1,630mg per day should provide some insight into what to do
next. Many people may find that 1600+mg is sufficiently high enough to have a positive
effect on their overall symptoms.

Options moving forward

Although 1,600mg+ is considered a high dose, some people may benefit from increasing that
even further. The best way to identify whether one would benefit or not is to experiment
with increasing the dosage and monitoring symptoms.

Increasing the dosage may include any of the following:

• Adding in one or two extra capsules of ThiaMega to reach 2000mg or 2400mg

• Increasing the dose of Thiamax in spread-out dosages
• Adding in a generic brand of benfotiamine or thiamine hydrochloride, taken in spread-out
doses throughout the day (AM, noon & PM)
• Some studies use up to 4500mg of thiamine (in hydrochloride form), although anecdotal
experience suggests that 2000-2500mg per day is the highest amount required to see
benefits.

When to reduce the dose?

Some people find only 1-2 months or mega doses are sufficient to replete low levels.
Negative symptoms can begin to occur such as jitteriness, anxiety, or insomnia if
someone is taking too much thiamine. In this case, the dosage can gradually be reduced
at a similar rate to how it was initially increased, and symptoms should be monitored.

On the other hand, some people may require this therapy for up to (and beyond) one
year. This includes those with complex chronic conditions who have witnessed
significant benefits from consistent mega dosing. This therapy may help to manage their
condition in the long-term.

Copyright © 2022 Elliot Overton 24

Generic Thiamine Megadose Protocol

Who is this protocol for?

• People with chronic health conditions which may be responsive to high doses of thiamine,
who might have tried a lower dose of thiamine derivative supplements and tolerated them
well.

• Applicable conditions may include: Thiamine deficiency, Neurodegeneration, Parkinson’s,

Multiple Sclerosis, Huntington’s, Postural Orthostatic Tachycardia Syndrome, Chronic
Fatigue Syndrome, Fibromyalgia, Inflammatory Bowel Disease

Protocol key points

• Any form of thiamine can be used. You may choose to use only one form, or a combination of
multiple forms (which I recommend). This can be adapted to only include thiamine
hydrochloride for people who do not tolerate the derivatives.
• Any brand will suffice.
• These are example doses only and can be modified based on individual tolerance. Some people
may need to increase at much slower rates than stated below
• If you are not using Objective Nutrients products, is highly advised that one becomes familiar
with the recommendations in Part 2 of this document to address associated nutritional
indications (including other minerals such as potassium & molybdenum etc)

Recommended nutrients

Thiamine hydrochloride powder

TTFD &/or Benfotiamine &/or Sulbutiamine

Multi B vitamin complex

Magnesium (taurate, glycinate or malate)

Copyright © 2022 Elliot Overton 25

Stage 1 (approx. days 0-7)
• The starting dose of thiamine for this protocol is 400mg. The concept is to gradually
build up the dose each week. If 400mg is tolerated, move onto stage 2

Supplement Breakfast Noon Evening

Thiamine HCL 100mg

Benfotiamine 200mg

TTFD &/or Sulbutiamine 100mg

B complex Dose on bottle

Magnesium 200mg 100-200mg

Stage 2 (approx. day 7+)

• Gradually double the dose of benfotiamine, TTFD and thiamine HCL.
• After achieving this the total dose of thiamine is approximately 600mg per day

Supplement Breakfast Noon Evening

Thiamine HCL 100mg 100mg

Benfotiamine 200mg

TTFD &/or Sulbutiamine 100mg 100mg

B complex Dose on bottle

Magnesium 200mg 100-200mg

Copyright © 2022 Elliot Overton 26

Stage 3 (approx. day 14+)
• Gradually double the dose of benfotiamine and increase thiamine hydrochloride to
200mg three times per day.
• The dose of thiamine for this stage is approximately 1200mg per day

Supplement Breakfast Noon Evening

Thiamine HCL 200mg 200mg 200mg

Benfotiamine 200mg 200mg

TTFD &/or Sulbutiamine 100mg 100mg

B complex Dose on bottle

Magnesium 200mg 100-200mg

Stage 4 (approx. day 21+)

• Gradually increase the dosage of benfotiamine and double the dosage of TTFD (or
sulbutiamine).
• This brings the dose of thiamine to 1600mg per day

Supplement Breakfast Noon Evening

Thiamine HCL 200mg 200mg 200mg

Benfotiamine 300mg 300mg

TTFD &/or Sulbutiamine 200mg 200mg

B complex Dose on bottle

Magnesium 200mg 100-200mg

Copyright © 2022 Elliot Overton 27

 Month 2 (day 30+)
At least one full week at 1,600mg per day should provide some insight into what to do
next. Many people may find that 1600+mg is sufficiently high enough to have a positive
effect on their overall symptoms.

Options moving forward

Although 1,600mg+ is considered a high dose, some people may benefit from increasing that
even further. The best way to identify whether one would benefit or not is to experiment
with increasing the dosage and monitoring symptoms.

Increasing the dosage may include any of the following:

• Adding in one or two extra capsules of any of the derivatives to reach 2000mg or 2400mg
• Increasing the dose of Thiamax in spread-out dosages
• Adding in a generic brand of benfotiamine or thiamine hydrochloride, taken in spread-out
doses throughout the day (AM, noon & PM)
• Some studies use up to 4500mg of thiamine (in hydrochloride form), although anecdotal
experience suggests that 2000-2500mg per day is the highest amount required to see
benefits.

When to reduce the dose?

Some people find only 1-2 months or mega doses are sufficient to replete low levels.
Negative symptoms can begin to occur such as jitteriness, anxiety, or insomnia if
someone is taking too much thiamine. In this case, the dosage can gradually be reduced
at a similar rate to how it was initially increased, and symptoms should be monitored.

On the other hand, some people may require this therapy for up to (and beyond) one
year. This includes those with complex chronic conditions who have witnessed
significant benefits from consistent mega dosing. This therapy may help to manage their
condition in the long-term.

Copyright © 2022 Elliot Overton 28

 Objective Nutrients Sensitive
Protocol
Who is this protocol for?
• People who have identified thiamine deficiency through testing or suspect deficiency
through symptom presentation

• People who have tried thiamine supplementation and experience strong negative
symptoms

• People who consider themselves sensitive to different supplements

Protocol key points

• Start at a low dose and increase very slowly. Faster is not better!
• Do not increase the dose if symptoms worsen. Only increase the dose once you have
returned to symptom baseline (refer to the section on paradoxical reactions for more
information)
• May require extra supplementation of other nutrients for tolerance. Please refer to
Document 2 for specific examples of nutrient indications.
• I recommend purchasing a milligram scale for accurate dosing in the early stages
• Thiamine hydrochloride is less potent and is initially used as a preparation to build
tolerance to more potent thiamine derivatives

Complete Basic Protocol Package

Thiamax (TTFD)

ThiActive B or Thiavite

ThiAssist mineral complex

Thiamine hydrochloride (any brand)

Copyright © 2022 Elliot Overton 29

 Stage 1 (approx. lasting 1 week)
• Start with a small dose of thiamine hydrochloride (10-50mg), full dose of ThiAssist
mineral complex and ¼ to ½ capsule of the B complex
• Gradually increase Thiamine HCL by 10-20mg each day (as tolerated)

Supplement Breakfast Noon Evening Extra info

10-50mg
Increase by 10-
Thiamine HCL working to
20mg per day
200mg
Taken with
ThiAssist 1 scoop 1 scoop
food

ThiActive B Complex ¼ to ½ capsule

Thiamax

Stage 2 (at 200mg thiamine HCL)

• After reaching 200mg of thiamine HCL, gradually increase B complex to 1 capsule.
• Continue increasing thiamine HCL by approx. 20-30mg per day

Supplement Breakfast Noon Evening Extra info

Increase by
Thiamine HCL 100mg 100mg
25mg per day

Taken with
ThiAssist 1 scoop 1 scoop
food
Increasing to 1
ThiActive B Complex
capsule

Thiamax

Copyright © 2022 Elliot Overton 30

 Stage 3 (at 400mg thiamine HCL)
• After reaching one full cap of B complex and 400mg of thiamine HCL
• Add in ¼ or ½ capsule of Thiamax and increase every few days until reaching one full
cap

Supplement Breakfast Noon Evening Extra info

Thiamine HCL 200mg 200mg

Taken with
ThiAssist 1 scoop 1 scoop
food

ThiActive B 1 capsule

Increase
¼ working to 1
Thiamax gradually every
full cap
few days

Reassessment
At this stage it would be wise to reassess symptoms and tolerance to the ongoing
supplement regime. If tolerating everything well, simply move to Stage 4.

On the other hand, if experiencing significant negative symptoms from taking Thiamax and
ThiActive B / Thiavite, it is advised to compare symptoms with the information in Part 2 of
this document because there may be an additional need for specific nutrients. This may
include a higher dose of molybdenum, the addition of glutathione support, or extra
electrolytes such as potassium.

If symptoms and lack of tolerance persist, you may not be “compatible” with TTFD for some
unknown reason.

Potential options in this case would be:

• Switching Thiamax for benfotiamine because of its lower sulfur content

• Switching ThiaActive B for another B complex not including TTFD
• If you are very sensitive to supplements in general, switch to Sensitive Protocol B

Copyright © 2022 Elliot Overton 31

 Stage 4 (at 1 full cap Thiamax)
• If Thiamax is tolerated well at 1 full cap per day, begin to increase to a second full
capsule gradually by ¼ or ½ every few days.

Supplement Breakfast Noon Evening Extra info

Thiamine HCL 200mg 200mg

Taken with
ThiAssist 1 scoop 1 scoop
food

ThiActive B 1 capsule

Increase
¼ working to 1
Thiamax 1 capsule gradually every
full cap
few days

Stage 5 (at 2 full caps Thiamax)

• If Thiamax is tolerated well at 1 full cap per day, begin to increase to a second full
capsule gradually by ¼ or ½ every few days.
• ThiActive B can be continued at 1 cap or increase to 2 caps per day in the morning

Supplement Breakfast Noon Evening Extra info

Can be continued
Thiamine HCL 200mg 200mg or gradually
discontinued

Taken with
ThiAssist 1 scoop 1 scoop
food

ThiActive B 1 capsule

Increase
1 increasing to 1 increasing to
Thiamax gradually every
2 capsules 2 capsules
few days

Copyright © 2022 Elliot Overton 32

 Stage 6 (4 caps Thiamax)
The total dose of thiamine at this stage of the protocol is between 400mg and 800mg
(depending on whether thiamine HCL was discontinued or not)

Options moving forward

Although some people may have experienced significant improvements, others may benefit
from increasing the dosage even further. The best way to identify whether one would benefit
or not is to experiment with increasing the dosage and monitoring symptoms.

Ways to increase the dosage may involve any of the following:

• Switching to the Objective Nutrients Megadose or Generic Megadose Protocol (entering at

week 2)
• Further increasing the dosage of Thiamax
• Adding in a generic brand of benfotiamine or thiamine hydrochloride, taken in spread-out
doses throughout the day (AM, noon & PM)
• Some studies use up to 4500mg of thiamine (in hydrochloride form), although anecdotal
experience suggests that 2000-2500mg per day is the highest amount required to see
benefits.

When to reduce the dose?

Some people find only 1-2 months of taking thiamine are sufficient to replete low levels.
Negative symptoms can begin to occur such as jitteriness, anxiety, or insomnia if someone
is taking too much thiamine. In this case, the dosage can gradually be reduced at a similar
rate to how it was initially increased, and symptoms should be monitored.

On the other hand, others may be required to consume high doses for upwards of one year
to fully recover from a severe nutritional deficiency. Everyone is biochemically unique, and
so their response to this therapy is difficult to anticipate.

Copyright © 2022 Elliot Overton 33

 Who is this protocol for?
• People who have identified thiamine deficiency through testing or suspect deficiency
through symptom presentation

• People who have tried thiamine supplementation and experience strong negative
symptoms

• People who consider themselves sensitive to different supplements

Protocol key points

• Start at a low dose and increase very slowly. Faster is not better!
• Do not increase the dose if symptoms worsen. Only increase the dose once you have
returned to symptom baseline (refer to the section on paradoxical reactions for more
information)
• If not using Objective Nutrients products, other nutrients are highly advised for those
experiencing side effects. Refer to Part 2 of this document
• I recommend purchasing a milligram scale for accurate dosing in the early stages
• If derivatives are not tolerated, use thiamine hydrochloride instead

Recommended nutrients

Thiamine hydrochloride powder

One or more thiamine derivatives (benfotiamine,

TTFD and/or sulbutiamine)

Multi B vitamin complex

Magnesium (taurate, glycinate or malate

Copyright © 2022 Elliot Overton 34

 Stage 1 (approx. lasting 1 week)
• Start with a small dose of thiamine hydrochloride (10-50mg), 300-500mg of
magnesium and ¼ to ½ dose of a B complex
• Gradually increase Thiamine HCL by 10-20mg each day (as tolerated)

Supplement Breakfast Noon Evening Extra info

10-50mg
Increase by 10-
Thiamine HCL working to
20mg per day
200mg

Magnesium 200mg 100-200mg

¼ to ½ dose
B Complex
on bottle

Thiamine derivative

Stage 2 (at 200mg thiamine HCL)

• After reaching 200mg of thiamine HCL, gradually increase B complex to 1 full dose.
• Continue increasing thiamine HCL by approx. 20-30mg per day

Supplement Breakfast Noon Evening Extra info

Increase by
Thiamine HCL 100mg 100mg
25mg per day

Magnesium 200mg 100-200mg

Working to 1
B Complex
full dose

Thiamine derivative

Copyright © 2022 Elliot Overton 35

 Stage 3 (at 400mg thiamine HCL)
• After reaching one full cap of B complex and 400mg of thiamine HCL
• Add in 25mg of your chosen thiamine derivative and increase every few days until
reaching 100mg

Supplement Breakfast Noon Evening Extra info

Thiamine HCL 200mg 200mg

Magnesium 200mg 100-200mg

B Complex 1 full dose

25mg Increase
Thiamine derivative increasing to gradually every
100mg few days

Reassessment
At this stage it would be wise to reassess symptoms and tolerance to the ongoing
supplement regime. If tolerating everything well, simply move to Stage 4.

On the other hand, if experiencing significant negative symptoms from taking the thiamine
derivative, it is advised to compare symptoms with the information in Part 2 of this
document because there may be an additional need for specific nutrients. This may include a
higher dose of molybdenum, the addition of glutathione support, or extra electrolytes such
as potassium.

If symptoms and lack of tolerance persist, you may not be “compatible” with thiamine
derivatives for some unknown reason.

The best option would be:

• Remove all supplements containing thiamine derivatives and replace them with
thiamine hydrochloride only
• Consider experimenting with sublingual lozenges containing thiamine
pyrophosphate

Copyright © 2022 Elliot Overton 36

 Stage 4 (at 100mg of thiamine derivative)
• If 100mg of the chosen thiamine derivative is tolerated well, begin to increase to
200mg by increments of 25mg every few days

Supplement Breakfast Noon Evening Extra info

Thiamine HCL 200mg 200mg

Magnesium 200mg 100-200mg

B Complex 1 full dose

25mg Increase
Thiamine derivative 100mg increasing to gradually every
100mg few days

Stage 5 (at 200mg of thiamine derivative)

• If 200mg is tolerated, begin to increase to 400mg in total per day

Supplement Breakfast Noon Evening Extra info

Can be continued
Thiamine HCL 200mg 200mg or gradually
discontinued

Magnesium 200mg 100-200mg

B Complex 1 capsule

100mg 100mg Increase

Thiamine derivative increasing to increasing to gradually every
200mg 200mg few days

Copyright © 2022 Elliot Overton 37

 Stage 6 (400mg of thiamine derivative)
• The total dose of thiamine at this stage of the protocol is between 400mg and
800mg (depending on whether thiamine HCL was discontinued or not)

Options moving forward

Although some people may have experienced significant improvements, others may benefit
from increasing the dosage even further. The best way to identify whether one would
benefit or not is to experiment with increasing the dosage and monitoring symptoms.

Ways to increase the dosage may involve any of the following:

• Switching to the Objective Nutrients Megadose or the Generic Megadose Protocol

(entering at week 2)
• Further increasing the dosage of Thiamax
• Adding in a generic brand of benfotiamine or thiamine hydrochloride, taken in spread-out
doses throughout the day (AM, noon & PM)
• Some studies use up to 4500mg of thiamine (in hydrochloride form), although anecdotal
experience suggests that 2000-2500mg per day is the highest amount required to see
benefits.

When to reduce the dose?

Some people find only 1-2 months of taking thiamine are sufficient to replete low levels.
Negative symptoms can begin to occur such as jitteriness, anxiety, or insomnia if
someone is taking too much thiamine. In this case, the dosage can gradually be reduced
at a similar rate to how it was initially increased, and symptoms should be monitored.

On the other hand, others may be required to consume high doses for upwards of one
year to fully recover from a severe nutritional deficiency. Everyone is biochemically
unique, and so their response to this therapy is difficult to anticipate.

Copyright © 2022 Elliot Overton 38

 Some people do not respond to thiamine
No matter how high the dose is, some individuals presenting with symptoms that match
thiamine deficiency (or indicate an increased need for this vitamin) are non-responsive to
thiamine.

• If you have tried the Mega Dose protocol, have increased beyond 2000mg, and still
perceive zero change in symptoms, then continuing to pursue this endeavour may be
fruitless. In other words, thiamine will likely not be effective at improving the symptoms.

• In this case, it would be best to investigate other causes for the present health condition
and symptoms under the guidance of a qualified healthcare provider.

Possible reasons for non-responsiveness

• A deficiency or functional deficiency is not present.
• Severe digestive malabsorption (in which case IM/I.V may be indicated)
• Other nutritional deficiencies impairing the action of thiamine (for example riboflavin,
biotin, niacin)
• If thiamine continues to worsen symptoms significantly (even at very low doses), severe
mitochondrial dysfunction/damaged mitochondria is possible. One cause of this may be due
to severe adverse reactions to medications. In this context, protocols aimed at clearing
defective mitochondria and maximizing mitochondrial biogenesis may be necessary (such
as fasting, NAD+, resveratrol) before re-attempting a thiamine protocol.

Conditions that can mimic thiamine deficiency

• Chronic inflammatory response syndrome (CIRS), chronic Lyme disease, mold exposure
or some other chronic infection such as bartonella
• Hypothyroidism
• Neurological autoimmunity including Parkinson’s and multiple sclerosis
• Vitamin B12 deficiency
• Environmental toxic exposure including heavy metals and man-made chemicals

Copyright © 2022 Elliot Overton 39

3. Protocols for thiamine-responsive
health conditions

Copyright © 2022 Elliot Overton 40

 Gastrointestinal Conditions
All protocols should be taken with an appropriate dose of magnesium
and a B complex of choice

IBS-C & Small Intestinal Bacterial

Overgrowth (constipation)

Key features of this condition

An overgrowth of bacteria in the small intestine is one of the most
common causes of irritable bowel-type symptoms. Bacterial
fermentation of dietary components leads to gas production whilst
bacterial metabolites can lead to irritation of the gut wall and
intestinal permeability.

A primary cause of SIBO is dysfunctional intestinal motility,

rendering the gut unable to clear bacteria through ordinary “clean
out” mechanisms.

Common signs and symptoms

• Slow intestinal motility and constipation, infrequent bowel movements
• Hard or dry stools
• Bloating, abdominal discomfort and excessive flatulence

Therapy aims:
• Improve communication from the brain to the gut through
the vagus nerve
• Increase digestive motility through support acetylcholine
• Support digestion and assimilation of dietary components

Copyright © 2022 Elliot Overton 41

 Recommended nutrients, dosage & mechanism
of action

Thiamine (TTFD is Bacopa monierri

preferred)

Full spectrum digestive

Atrantil
enzyme

Pantothenic acid TUDCA

Enhancing acetylcholine in enteric neurons

• Thiamine (TTFD is preferred for this function): 100mg increasing to 300-500mg per
day
• Pantothenic acid: 1000-1500mg per day
• Bacopa monierri: 300mg per day

Increasing intestinal motility

•

Supporting digestion of dietary components

• Full spectrum pancreatic enzyme: 1-2 caps with each meal
• TUDCA (to improve bile flow): 2000-3000mg per day

Important points
This protocol is often sufficient for people who’s SIBO is caused primarily by poor
motility and may not be sufficient for other causes. Once motility is restored,
SIBO/bacterial overgrowth may still require eradication with antimicrobials.

TTFD is the most effective form for improving digestive motility, although people with
certain forms of dysbiosis may react negative to the sulfur content of this molecule. In
that case, switch TTFD with benfotiamine.

Copyright © 2022 Elliot Overton 42

 Hypochlorhydria (low stomach acid),
GERD, or gastroparesis

Key features
Although three distinct conditions, research shows that each can
be driven by underlying autonomic nervous system dysfunction
and poor cholinergic tone.

The interface between the vagus nerve and the enteric nervous
system governs stomach acid output, sphincter control, and
stomach motility.

Common signs and symptoms

• Upper bloating, nausea after meals, frequent belching
• Acid reflux, discomfort around the area of the stomach
• Loss of appetite, feeling full quickly after each

Therapy aims:
• Improve communication between the brain and the
stomach through enhancing vagus nerve activity
• Increasing stomach muscle motility and fluid secretion
• Improving stomach acid levels through temporary acid
supplementation

Copyright © 2022 Elliot Overton 43

 Recommended nutrients, dosage & mechanism
of action

Thiamine (TTFD is Ginger extract

recommended)

CDP choline Betaine HCL w/ pepsin

Pantetheine or Bacopa monnieri

Pantothenic acid

Peppermint oil Niacin (possibly)

Acetylcholine precursors
• CDP Choline: 500-750mg per day
• Pantothenic acid: 1000-1500mg per day

Enhancing action of acetylcholine

• Thiamine (TTFD is preferred for this function): 100mg increasing to 400-600mg per
day
• Bacopa monnieri extract (decreases acetylcholine breakdown): 300mg per day

Optimizing stomach acidity

• Betaine HCL w/ pepsin: 600-1200mg per meal
• Possibly niacin: 100mg increasing to up to 1000mg per day

Increasing stomach motility & emptying

• Ginger root extract: 500-750mg per day
• Food-grade peppermint oil: 10ml per day

Important points
This protocol is often sufficient for people whose stomach dysfunction is caused
primarily vagus nerve dysfunction. If symptoms are non-responsive to this protocol, it
is advised to test for H.Pylori (breath test & stool antigen) to rule out infectious cause.

Copyright © 2022 Elliot Overton 44

 Cholestasis, liver, or gallbladder
insufficiency

Cholestasis refers to a “backlog” of bile in the liver and difficulty

exporting waste products into the gut through the gallbladder. Poor
bile flow can be caused by structural changes to the liver such as an
obstruction or infection.

However, if mild, it can be a “functional problem” related to

underlying nutritional status, inflammation, and oxidative stress.

Common signs and symptoms

• Pale stools, nausea, or diarrhoea when eating fats
• Undigested fats in stools, abdominal discomfort, or pain in upper right quadrant
• Bloating and nausea, dark urine, itchiness

Therapy aims:
• Increase synthesis of new bile acids and improve quality of
bile
• Improve digestion and assimilation of dietary fats
• Enhance secretion of bile through the gallbladder

Copyright © 2022 Elliot Overton 45

 Recommended nutrients, dosage & mechanism
of action

• Taurine: 3000mg per day

• Glycine: 5000-10,000mg per day
• TUDCA:2000mg in spread out doses per day

• Thiamine (TTFD is preferred for this function): 100mg increasing to 300-400mg per
day
• Pantothenic acid or pantetheine: 1000-1500mg per day

• Digestive bitters: one dose before each meal

• Artichoke extract: 2000-3000mg per day

• Pancreatic lipase: 1 capsule with each meal

Although very mild cholestasis and gallbladder dysfunction is somewhat common,

genuine diseases of these organs can constitute medical emergency and require medical
attention.

Copyright © 2022 Elliot Overton 46

 Intestinal Permeability

Key features of this condition

Elevated intestinal permeability refers to an opening up of the tight
junctions in the intestinal wall, leading to increased passage of
intestinal contents through the intestinal barrier. This is found in a
variety of chronic health conditions and is a key risk factor for
autoimmunity.

It can be identified via various tests including:

• PEG or lactulose breath test
• Elevated stool zonulin levels

Common signs and symptoms

• Can be asymptomatic, or can manifest as practically any type of symptom
• Chronic diarrhea, constipation, bloating and digestive issues
• Underlying nutritional deficiencies
• Fatigue, headaches, brain fog after eating
• Acne, rosacea, rash, or eczema
• Chronic pain
• Autoimmunity of any kind

Therapy aims:
• Improve energy metabolism in the intestinal cells &
vagus nerve activity
• Reduce intestinal oxidative stress and inflammation
• Provide raw material for re-building the intestinal barrier

Copyright © 2022 Elliot Overton 47

 Recommended nutrients, dosage & mechanism
of action

Thiamine (TTFD is Bacillus coagulans

recommended) probiotic

L-Glutamine BPC-157 peptide

Sodium butyrate Colostrum or serum-

derived immunoglobulin

Support energy metabolism of the intestinal cells & enhancing

vagus activity
• Sodium butyrate: 1,200-1,800mg per day
• Thiamine: 100-300mg per day

Provide raw material for re-building intestinal barrier

• BPC-157 peptide: 250mcg twice per day away from meals
• L-Glutamine powder: 15-25 grams per day away from food

Reduce inflammation and oxidative stress

• Liposomal colostrum (or serum derived immunoglobulin): dose on bottle
• Bacillus coagulans: dose on bottle

Important points
Intestinal permeability has numerous causes. This protocol may be sufficient for
temporarily repairing damage to the barrier and restore barrier function. However, the
root cause needs to be investigated and one should consider:
• Potential gut infections
• Optimizing circadian rhythm
• Addressing metabolic syndrome
• Identifying food sensitivities

Copyright © 2022 Elliot Overton 48

 Neurological Conditions
All protocols should be taken with an appropriate dose of magnesium
and a B complex of choice

Neuropathy & Nerve pain

A combination of oxidative stress and inflammation can

cause damage to peripheral nerves and sensory receptors,
leading to excess or inappropriate nerve firing.
It can be caused by nutritional deficiencies, toxic exposure
(chemicals, alcoholism, drug side effects, or vitamin B6
excess), hyperglycaemia, and infections of various kinds.

Common signs and symptoms

• Burning, aching, stinging, stabbing, or shooting pain in the periphery (arms, legs)
• Numbness and tingling, difficulty with coordination or balance
• Muscle weakness or limb weakness

Therapy aims:
• Reducing peripheral nerve inflammation if present
• Enhancing neuronal energy metabolism
• Reducing peripheral oxidative stress while addressing the
root cause

Copyright © 2022 Elliot Overton 49

 Recommended nutrients, dosage & mechanism
of action
Thiamine (benfotiamine Nigella sativa (black
is recommended) seed oil)

R-Alpha lipoic acid Agmatine sulfate

Liposomal glutathione Kudzu root& Lion’s mane

mushroom

• Nigella sativa (black seed oil): 1 tsp 2-3 times per day
• Pueraria lobata (kudzu root): 500mg 3 times per day [or equivalent in tincture]
• Lion’s mane mushroom: 1000mg 3 times per day
• Agmatine sulfate: 1000-3000mg per day [not available in Europe]

• Benfotiamine: 300-1500mg per day

• R-Alpha lipoic acid: 300-900mg per day

• Liposomal glutathione: 500-1500mg per day on empty stomach

• Also consider vitamin C and liposomal curcumin

The root cause should be established. This can be caused by underlying deficiencies of
thiamine, vitamin B6, and B12. Diabetes is another driving factor behind different forms
neuropathy. Furthermore, chronic infections such as Lyme and Bartonella are common
drivers.

Copyright © 2022 Elliot Overton 50

 Brain-fog, lack of concentration or mild
cognitive impairment

Key features
These difficulties become more common with age but can
also occur because of underlying nutritional and
neurochemical imbalances.

Methylation imbalance is a common cause and should be

assessed through testing.

Common signs and symptoms

• Difficulty finding words, poor memory, forgetful
• Lose-track of thought process, unable to think properly
• Difficulty conducting basic mental tasks

Therapy aims:
• Enhance cholinergic and dopaminergic output
• Support neurogenesis
• Support delivery of nutrients and clearance of waste
from the brain

Copyright © 2022 Elliot Overton 51

 Recommended nutrients, dosage & mechanism
of action
Thiamine (TTFD, Lion’s mane mushroom &
sulbutiamine or benfo) Rhodiola rosea

Alpha GPC or CDP N-acetyl tyrosine

choline
Uridine Monophosphate Gingko biloba

Enhance cholinergic and dopaminergic output

• Alpha GPC or CDP choline: 500-750mg per day
• TTFD or sulbutiamine: 300-500mg per day (if using benfotiamine, 300-1,200mg per
day)
• N-acetyl tyrosine: 500-1000mg per day
• Uridine monophosphate: 600mg per day

Support neurogenesis
• Lion’s mane: 3000mg per day
• Rhodiola rosea root: 3000-6000mg per day

Improve nutrient delivery and clearance of waste

• Gingko biloba: 3 gram (equivalent in tincture) twice per day

Copyright © 2022 Elliot Overton 52

 Multiple Sclerosis

Key features of this condition

MS is a neuroinflammatory autoimmune disease involving
auto-antibodies against the myelin sheath, leading to
progressive demyelination and neurodegeneration.

As an autoimmune condition, focusing on reducing all

potentially immuno-reactive dietary elements and
addressing intestinal permeability is top priority.

Common signs and symptoms

• Mobility problems, loss of coordination, muscle spasms and muscle stiffness
• Fatigue, neuropathy, and poor vision
• Poor concentration, autonomic nervous system dysfunction

Therapy aims:
• Improve mitochondrial function
• Reduce neuroinflammatory process
• Support myelination

Copyright © 2022 Elliot Overton 53

 Recommended nutrients, dosage & mechanism
of action

TTFD and benfotiamine Nicotinamide riboside

Biotin Acetyl-L-carnitine

N-acetyl cysteine (NAC) Vitamin B12

CoQ10 Melatonin

Improve mitochondrial function

• Coenzyme Q10: 300-1000mg per day
• Benfotiamine: 600-1200mg per day
• Nicotinamide riboside: 300-900mg per day
• Acetyl-L-carnitine: 1000-1500mg per day

Reduce neuroinflammatory process

• NAC: 600-1200mg per day
• Melatonin: 5-10mg per night

Support myelination
• Biotin (extremely high dose): 5000-35,000microgram per day (supervision advised)
• TTFD: 300-1000mg per day
• Vitamin B12 (methylcobalamin): 1000-10,000 microgram per day (supervision
advised)

Important points
This protocol may help with symptoms, but the underlying cause of autoimmunity
should be investigated and addressed. Strict dietary intervention is essential in this
context.

Copyright © 2022 Elliot Overton 54

 Parkinson’s Disease

Key features of this condition

Parkinson’s is a progressive neuroinflammatory disease
involving degeneration of dopamine-producing nerve
cells in a region of the brain called the substantia nigra,
leading to progressive demyelination and
neurodegeneration.

Mitochondrial dysfunction, oxidative stress and low-

level inflammation of the brain are involved in the
progression of this condition.

Common signs and symptoms

• Tremors, muscle stiffness or jerks
• Impaired balance and motor coordination
• Slurred speech, stuttering or difficulty with pronunciation
• Progressive decline in neurological function

Therapy aims:
• Improve mitochondrial function
• Increase dopamine output
• Reduce neuroexcitotoxicity and oxidative stress

Copyright © 2022 Elliot Overton 55

 Recommended nutrients, dosage & mechanism
of action
Thiamine HCL, Nicotinamide riboside
sulbutiamine and TTFD

Arginine alpha N-acetyl tyrosine

ketoglutarate

Magnesium L-threonate N-acetylcysteine (NAC)

Coenzyme Q10 Agmatine sulfate

Improve mitochondrial function

• Coenzyme Q10: 300-1000mg per day
• Arginine alpha-ketoglutarate: 1000-3000mg per day
• Nicotinamide riboside: 300-300mg per day
• Thiamine HCL: 1500-2000mg per day

Increase dopamine output

• TTFD: 100-400mg per day
• Sulbutiamine: 100-400mg per day
• N-acetyl tyrosine: 500mg per day (caution)

Reduce exctitoxicity and oxidative stress

• NAC: 600-1200mg per day
• Agmatine sulfate (not available in EU/UK): 1000-3000mg per day
• Magnesium L-threonate: 200mg per day (elemental magnesium content)

Important points
CAUTION must be taken if consuming B complex (specifically vitamin B6) and N-
acetyl-tyrosine in conjunction with L-dopa (and similar medications). MUST review
with physician.

Copyright © 2022 Elliot Overton 56

 Postural Orthostatic Tachycardia
Syndrome

Key features of this condition

POTS is a form of autonomic nervous system dysfunction which
involves faulty control of the peripheral blood vessels. Abnormal
dilation or constriction of the vasculature results in poor blood
flow to the brain, leading to a variety of hormonal responses to
counteract this effect.

Poor communication between the brain and the periphery

through the vagus nerve can be one underlying cause of this
condition.

Common signs and symptoms

• Rapid heartbeat (tachycardia) and light-headedness, especially upon exertion
• Can fluctuate between high/low blood pressure and feeling faint
• Inability to exercise and fatigue
• Headaches, dizziness, excessive thirst, sweating, and changes in body temperature
• Peripheral blood pooling, blotchy skin, blue/purple hands or feet, and poor circulation

Therapy aims:
• Enhance vagus nerve activity through support
cholinergic output
• Replenish lost electrolytes where necessary

Copyright © 2022 Elliot Overton 57

 Recommended nutrients, dosage & mechanism
of action

Thiamine (TTFD or Acetyl-L-carnitine

benfotiamine)

Alpha GPC or CDP Bacopa monnieri

choline

Pantothenic acid Magnesium L-threonate

Enhance vagus nerve activity and cholinergic output

• Thiamine (TTFD): 300-600mg per day
• Thiamine (if using benfotiamine): 600-1200mg per day
• CDP choline or Alpha GPC: 500-750mg per day
• Bacopa monnieri: 300-600 mg per day
• Magnesium L-threonate: 300mg (elemental magnesium)
• Acetyl-L-carnitine: 1500mg per day
• Pantothenic acid: 1000-1500mg per day

Replenish lost electrolytes where necessary

• Many people suffering from POTS have an increased need for sodium. This can be
anywhere from 3-8 grams, and even higher for some people.

Important points
There are several different forms of POTS which may need to be treated differently.
This protocol only focuses on using thiamine and supportive nutrients to support the
autonomic nervous system.
Dr Derrick Lonsdale found that thiamine deficiency was common among all his POTS
patients, and many responded positively to therapy with thiamine.

Copyright © 2022 Elliot Overton 58

 Generalized neuroinflammation of any
cause

Key features of this condition

Activation of resident immune cells in the brain can occur
due to waste products and other chemicals entering the
central nervous system through a leaky blood-brain-barrier.

This can initially present with cognitive impairment and

mild neurological dysfunction but can eventually lead to
systemic symptom presentation.

Common signs and symptoms

• Brain fog, lack of concentration, poor cognition, confusion, poor memory, depersonalization
• Autonomic nervous system dysfunction (chronic gut, bladder, circulation, heart rate, fluid
balance problems, dizziness, chronic thirst and frequent urination)
• Systemic inflammatory symptoms including chronic pain, fatigue, weakness

Therapy aims:
• Stabilize microglial (neuroimmune) cells
• Reduce neuroexcitotoxicity
• Support endogenous antioxidant system and lipid
replacement in the brain

Copyright © 2022 Elliot Overton 59

 Recommended nutrients, dosage & mechanism
of action
Thiamine (TTFD or Turkey tail mushroom &
sulbutiamine) Gou-teng herb

Phosphatidylcholine and Specialized pro-

PEA resolving mediators

Liposomal glutathione Agmatine sulfate

L-theanine and NAC Magnesium L-threonate

Stabilize microglia
• Specialized pro-resolving mediators: Dose on bottle
• Gou-Teng (Uncaria rhynchophylla): 6g (equivalent dose) in tincture, three times per
day
• Turkey tail mushroom: 2 grams three times per day
• Palmitoyl ethanolamide (PEA): 300-900mg per day

Reduce neuroexcitotoxicity
• L-theanine: 2000mg two to three times per day
• Agmatine sulfate: 1000-3000mg per day
• Magnesium L-threonate 200-300mg (elemental equivalent)
• Thiamine (TTFD or sulbutiamine): 100-400mg per day

Support endogenous antioxidant system and lipid replacement in

the brain
• Phosphatidylcholine: 1000-2000mg per day
• Liposomal glutathione: 500-1000mg per day
• N-acetylcysteine (NAC): 600-1200mg per day

Important points
It is essential to attempt to identify the underlying cause, which may include Chronic
Inflammatory Response Syndrome (biotoxins from infection or mold), stealth
pathogens, chronic intestinal permeability and gut dysfunction, or chemical / heavy
metal toxicity. It can also occur as the result of traumatic brain injury.

Copyright © 2022 Elliot Overton 60

 Cardiometabolic conditions
All protocols should be taken with an appropriate dose of magnesium
and a B complex of choice

Heart failure

Key features of this condition

This condition involves an inability of the heart muscles to
contract and pump blood through circulation at an appropriate
rate. Dysfunctional mitochondria play a central role in the
development of this condition.

Chronic dysfunction of the cells in the heart muscle can lead to

cardiogenic inflammation and eventual necrosis of tissue.

Common signs and symptoms

• Fast heart rate (tachycardia), edema, bloating and overall water retention
• Arrhythmia, shortness of breath, fatigue and weakness upon exertion
• Unexplained persistent cough, poor circulation to the peripheral organs

Therapy aims:
• Support energy metabolism within the heart muscle
• Improve blood flow to the heart
• Reduce oxidative stress

Copyright © 2022 Elliot Overton 61

 Recommended nutrients, dosage & mechanism
of action
Thiamine (TTFD or D-Ribose
sulbutiamine)

L-carnitine R-Alpha lipoic acid

Coenzyme Q10 Vitamin K2

Taurine & Creatine Hawthorne Extract

Support energy metabolism within the heart muscle

• D-Ribose: 5-15 grams per day
• TTFD: 200-300mg per day
• Coenzyme Q10: 500-1000mg per day (aim for blood levels of 3-3.5)
• L-Carnitine: 2000-4000mg per day
• Vitamin K2: 300mcg per day
• Creatine: 5 grams per day

Improve blood flow to the heart

• Aged garlic extract: 5-10 grams per day
• Hawthorne extract: 300-600mg per day

Reduce oxidative stress

• Taurine: 3000mg per day
• R-Alpha lipoic acid: 300-600mg per day

Important points
This condition is chronic, potentially life threatening, and the underlying causes must be
investigated through a cardiologist.

Copyright © 2022 Elliot Overton 62

 Hypertension and/or Angina

Key features
Two distinct conditions, both of which can feature
dysfunction of the endothelial layer of the blood vessels. In
angina, temporary reductions in circulation to the heart lead
to acute events of chest pain.

Hypertension is chronically high blood pressure, which can

occur as a result of the heart needing to work harder to push
blood through obstructed and/or dysfunction blood vessels.

Common signs and symptoms

Angina:
• Intermittent, acute chest pain upon exertion or at rest. Shortness of breath, dizziness,
fatigue, nausea and sweating.

• Chronically elevated blood pressure when measured. Often goes undiagnosed because of
low symptom profile.
• May present with are variety of symptoms including headaches, tinnitus, chest pain if
severe.

Therapy aims:
• Reduce vascular endothelial dysfunction (blood vessel
inflammation and oxidative stress)
• Increase synthesis of endothelial nitric oxide (the
primary blood vessel dilator)

Copyright © 2022 Elliot Overton 63

 Recommended nutrients, dosage & mechanism
of action
Thiamine (benfotiamine Hawthorne
preferred)

Aged garlic extract L-Citrulline & L-Arginine

R-Alpha lipoic acid Niacin (flush version)

Trimethylglycine Liposomal vitamin C

Reduce vascular endothelial dysfunction/inflammation

• Trimethylglycine: 1.5-2 grams per day
• Benfotiamine: 600-900mg per day
• R-Alpha lipoic acid: 300-900mg per day
• Niacin: 500mg potentially increasing up to 3000mg per day

Improve vascular nitric oxide synthesis to improve blood flow

• Liposomal vitamin C: 500-1000mg per day
• Hawthorne extract: 300-600mg per day
• Aged garlic extract: 5-10 grams per day
• L-Citrulline: 3 grams per day
• L-Arginine: 5-10 grams per day

Important points
This protocol should be combined with dietary and lifestyle changes. This includes all
the following
• Carbohydrate-restriction, ketogenic or animal-based diet
• Time-restricted feeding or intermittent fasting
• Regular strength training
• Maintaining a structured circadian rhythm

Copyright © 2022 Elliot Overton 64

 Diabetes Mellitus (type II)

Key features of this condition

Diabetes can be thought of as “energy overload”,
stemming from the cells inability to process energy at
the rate it is being consumed. This is demonstrated by
the high ratios of NADH:NAD, ATP:ADP, and acetyl-
CoA/CoA.

This can be improved via increasing the cells oxidation

of substrate through inducing an energy deficit, whilst
reducing insulin spikes and improving blood glucose
management.

Common signs and symptoms

• Increased thirst, frequent urination
• Poor immunity, frequent infections or slow healing lesions, skin tags, unintended weight gain
around abdomen
• Dizziness or spells of hypoglycemia, neuropathy

Diabetes can be thought of as “energy overload”, stemming from the cells inability to process energy at the
rate it is being consumed. This is demonstrated by the high ratios of NADH:NAD, ATP:ADP, and acetyl-
CoA/CoA.

Therapy aims:
This can be improved via increasing the cells oxidation of substrate through inducing an energy deficit,
whilst reducing insulin spikes and improving blood glucose management.

• Improve insulin signalling and sensitivity

• Improve cell energy metabolism/redox status
• Support endogenous antioxidant system

Copyright © 2022 Elliot Overton 65

 Recommended nutrients, dosage & mechanism
of action

Thiamine (benfotiamine Olive leaf extract &

recommended) Berberine

R-Alpha lipoic acid Nigella sativa

Glycine and NAC Myo-inositol

Improve insulin signalling and sensitivity

• Berberine (caution with diabetic medications): 1000-1500mg per day
• Myo-inositol: 3-4 grams per day

Improve cell energy metabolism/redox status

• Black seed oil (Nigella Sativa): 1 teaspoon 2 times per day
• R-alpha lipoic acid: 300-600mg
• Benfotiamine: 300-1500mg per day

Support endogenous antioxidant system

• Olive leaf extract: 500-1000mg per day
• Glycine: 5 grams per day
• NAC: 600-1200mg per day

Important points
This protocol must be combined with dietary and lifestyle changes. This includes all the
following
• Low carbohydrate, ketogenic or animal-based diet
• Time-restricted feeding or intermittent fasting
• Regular strength training
• Maintaining a structured circadian rhythm

Copyright © 2022 Elliot Overton 66

 Other Conditions
All protocols should be taken with an appropriate dose of magnesium
and a B complex of choice

Fibromyalgia

Key features of this condition

Research demonstrates that the symptoms of the condition are
caused by both issues stemming from cells both in the central
nervous system and the periphery. The nervous system becomes
hyper-responsive to sensory stimuli.

Central and peripheral markers of inflammation, mitochondrial

dysfunction and oxidative stress have been shown in research,
leading to “central sensitization” of the pain-detection system in the
brain.

Common signs and symptoms

• Chronic pain (burning, stinging, aching) in the muscles/skin along with hypersensitivities
• Chronic fatigue, digestive issues, and mood changes
• Insomnia and/or circadian rhythm dysregulation

Therapy aims:
• Improve cell energy metabolism to reduce local lactic
acidosis
• Support nerve function and reduce neuronal
excitotoxicity
• Reduce inflammation and oxidative stress

Copyright © 2022 Elliot Overton 67

 Recommended nutrients, dosage & mechanism
of action
Thiamine (multiple Coenzyme Q10
forms)

Calcium-D-glucarate Nicotinamide riboside

L-Carnitine Arginine alpha-

ketoglutarate
Liposomal GABA & Agmatine sulfate
Methylsufonyl methane

Improve energy metabolism to reduce local lactic acidosis

• Thiamine in different forms (benfotiamine, TTFD, HCL): up to 2500mg combined per
day
• Nicotinamide riboside: 300-900mg per day
• Coenzyme Q10: 300-900mg per day
• L-Carnitine: 3-5 grams per day
• Arginine alpha-ketoglutarate: 1500mg-3000mg per day

Support nerve function and reduce excitotoxicity

• Agmatine sulfate: 1500-3000mg per day
• Liposomal GABA (empty stomach): 500mg per day

Reduce inflammation and oxidative stress

• Methylsulfonylmethane: 2000-3000mg per day
• Consider: SAMe (300-600mg per day), liposomal vitamin C (250-1000mg per day),
CBD oil sublingually, topical magnesium spray and Epsom salts baths

Important points
Fibromyalgia is notoriously difficult and slow to improve. Thiamine can exert substantial
effects and operates through several mechanisms. Optimizing digestive function and
circadian rhythmicity is extremely important. Consider investigating chronic systemic
stealth infection also.

Copyright © 2022 Elliot Overton 68

 Chronic Fatigue Syndrome / Myalgic
Encephalomyelitis

Key features of this condition

Often referred to as a “mystery” by the conventional medical
system, chronic fatigue syndrome is debilitating and can
persist for decades if untreated.

Research has demonstrated severe dysfunction of

mitochondria, depleted pools of antioxidants, and a tendency
toward chronic systemic inflammation.

Common signs and symptoms

• Malaise, unrefreshing rest or sleep and extreme exhaustion
• Extreme fatigue and body pain (in some cases)
• Poor concentration, memory loss and cognitive impairment
• Sore throat and tender lymph nodes, headache, and numerous other potential symptoms

Therapy aims:
• Provide raw building blocks for ATP synthesis and
support ATP recycling
• Support mitochondrial function
• Provide antioxidant protection for mitochondria

Copyright © 2022 Elliot Overton 69

 Recommended nutrients, dosage & mechanism
of action
Thiamine (multiple PQQ and Vitamin K2
forms)

D-ribose L-carnitine

Nicotinamide riboside Coenzyme Q10

(ubiquinol)

Panax ginseng Creatine

Provide raw building blocks for ATP synthesis and support ATP
recycling
• D-ribose: 10-20 grams per day
• Creatine monophosphate: 5 grams per day

Support mitochondrial function

• Nicotinamide riboside: 300-900mg per day
• Thiamine HCL: 500-1000mg per day
• Benfotiamine: 300-600mg per day
• TTFD or sulbutiamine: 300-600mg per day
• L-carnitine: 2.5-4 grams per day
• Vitamin K2: 150-300mcg per day

Antioxidant protection for mitochondria

• Pyrroloquinoline quinone (PQQ): 20-30mg per day
• CoQ10 (ubiquinol): 300-900mg per day

Important points
CFS/ME is extremely complex, difficult to address and slow to improve. There is almost
always an underlying cause which can be identified. This is a MUST for this condition.
Consider any or all of the following:

• Chronic Inflammatory Response Syndrome (biotoxins from infection or mold)

• Stealth pathogens including Lyme, chronic viral infection
• Chemical/heavy metal toxicity

Copyright © 2022 Elliot Overton 70

 Interstitial Cystitis

Key features of this condition

Interstitial cystitis is a chronic urinary condition which can
present in a similar fashion to urinary tract infections, but in
the absence of infection.

It involves inflammation of the urinary tract, impaired

mucosal integrity and increased bladder permeability, and
damage to the bladder wall. Low levels of nitric oxide and
circulation to the bladder have also been

Common signs and symptoms

• Frequent or painful urination (stinging, burning, itching)
• Urinary incontinence or sudden, strong urge to urinate
• Pelvic pain, night-time urination, difficulty completing urinary

Therapy aims:
• Reduce inflammation and spasms of the bladder
• Improve nitric oxide synthesis and circulation
• Increase mucosal barrier integrity of the bladder wall

Copyright © 2022 Elliot Overton 71

 Recommended nutrients, dosage & mechanism
of action
Thiamine (TTFD Methylsulfonylmethane
recommended)

N-acetylglucosamine L-Arginine

Chondroitin sulfate L-Citrulline

Horsetail & Cleavers Aloe juice

herbs

Reduce inflammation & spasms

• Horsetail tincture: 2 gram equivalent 3 times per day
• Cleavers tincture: 3 gram equivalent 3 times per day
• TTFD: 200-300mg per day

Improve nitric oxide and circulation to the bladder

• L-Arginine: 2000-3000mg per day
• L-Citrulline: 1000-2000mg per day

Increase mucosal barrier integrity

• Chondroitin sulfate: 1200mg per day
• N-acetylglucosamine: 1400mg per day
• Methylsulfonylmethane: 2000-3000mg per day

Important points
Interstitial cystitis has numerous causes. The most common of which (that I have
personally found) is dietary oxalate overload. A low oxalate diet is therefore HIGHLY
recommended. Other causes may include:
• Stealth bladder infections
• Intestinal permeability
• Systemic infections such as Lyme or Bartonella
• Generalized autonomic nervous system dysfunction

Copyright © 2022 Elliot Overton 72

 Pre-menstrual syndrome

Key features of this condition

Period pain can be attributed to high levels of inflammatory
chemicals called prostaglandins, which enhance muscular
spasms of the uterus.

Furthermore, elevated levels of estrogen can be involved in

breast tenderness, mood changes, and skin problems.

Common signs and symptoms

• Breast tenderness, abdominal cramps, digestive distress around period
• Anxiety, insomnia, or emotional instability
• Acne, dry skin
• Heavy menstrual flow

Therapy aims:
• Reduce muscular spasms
• Improve hormonal balance (synthesis of progesterone,
detoxification and clearance of estrogens)

Copyright © 2022 Elliot Overton 73

 Recommended nutrients, dosage & mechanism
of action
Thiamine (any form) White peony root

Magnesium (extra around

Myo-inositol
menstruation)

Vitamin B6 Lemon balm (melissa

officinalis)

Calcium D-glucarate Vitex agnus castus

(possibly)

Reduce muscular spasms

• White peony root tincture: (3 gram equivalent) 3-4 times per day
• Lemon balm tincture: (1 gram equivalent) 1-2 times per day
• Magnesium: total dose of 400-800mg per day

Improve hormonal balance

• Myo-inositol: 6-12 grams per day in powder form
• Vitex agnus castus (if suspected low progesterone and/or high prolactin): (100-200mg
equivalent). This article is recommended
• Calcium D-glucarate – 2.5-3 grams per day
• Vitamin B6 – 20mg per day

Unknown mechanism of action

• Thiamine in any form: 300-500mg per day
[The mechanism of action is unknown. It may be working through anti-inflammatory,
antioxidant, spasmolytic effects. Over eight studies showed this therapy to be highly
effective for reducing both physical and mental PMS symptoms]

Important points
PMS can have numerous causes, but frequently involves estrogen dominance. For this
reason, addressing the underlying cause of estrogen dominance is often necessary. This
may include:
• Optimizing detoxification and clearance of estrogen through liver and gut
• Improving progesterone synthesis
• Identifying and removing internal or external estrogenic xenobiotics

Copyright © 2022 Elliot Overton 74

4. Identifying nutritional imbalances through
testing and symptom presentation

Copyright © 2022 Elliot Overton 75

 Testing for thiamine deficiency

Key points
• Serum or plasma thiamine testing is not recommended as this
measurement likely only reflects recent intake.

• Two of the most accurate testing methods are whole-blood

thiamine pyrophosphate, and red cell transketolase activity
w/TPP effect.

Potential caveats
• Relying solely on testing to identify thiamine-responsive conditions is problematic.
From a clinical perspective, many individuals respond to thiamine supplementation
despite normal test results. One reason for this may be due to regional deficiencies in
isolated organs or areas of the body, such as the heart and the brain.
• Inflammation, oxidative stress, and genetic factors may also increase the demand for
thiamine at the cellular level. This is unlikely to show up on any blood or urine test.
Nevertheless, below are some of the potential biomarkers which have associated
with thiamine deficiency and can be tested:

Copyright © 2022 Elliot Overton 76

 ✓

Copyright © 2022 Elliot Overton 77

 Magnesium
Symptoms of deficiency
• Poor appetite
• Tremors, anxiety or insomnia
• Arrhythmia or high blood pressure
• Numbness, tingling, muscle twitching, cramps/contractions
• Fatigue
• Low blood potassium & calcium
• Headache, dizziness

Nutritional interaction
Magnesium is necessary for the activation of thiamine to active thiamine
pyrophosphate (TPP) by the enzyme thiamine pyrophosphokinase. Both nutrients
share cofactor roles for the transketolase enzyme involved in the pentose phosphate
pathway. Furthermore, both are also necessary for two enzymes involved in energy
metabolism (pyruvate dehydrogenase and a-ketoglutarate dehydrogenase). High
doses of thiamine can lead to lower magnesium and/or increased magnesium demand,
and magnesium may be necessary for the retention of thiamine.

Possible intervention
• Increase the dose you are currently at by 100mg every few days to assess any
symptom changes. This may involve an overall increase of up to 400-600mg (in
addition to the 300-400mg taken as a normal part of the thiamine protocol)
• Aim to use bioavailable forms including malate, glycinate, threonate, taurate, or
alternatively Re-Mag.

Test type Test Low High

Blood RBC magnesium ✓

Blood Serum magnesium (less sensitive) ✓

Copyright © 2022 Elliot Overton 78

 Sodium
Symptoms of deficiency
• Low blood pressure
• Fatigue
• Headache
• Light headedness / dizziness
• Excessive urination and thirst
• Muscle pain, twitching, cramps
• Food cravings

Possible intervention
• Increase sodium by 3000-5000mg per day in the form of natural, unrefined
grey sea salt or rock salt.

Test type Test Low High

Blood Serum sodium ✓

If symptoms improve with increased salt

Experimentation
intake

Copyright © 2022 Elliot Overton 79

 Potassium

Symptoms of deficiency
• Fatigue
• Muscle cramps/ spasms, aches, weakness
• Heart palpitations / tachycardia / arrhythmia
• Shortness of breath
• Headache
• Light headedness / dizziness
• Excessive urination and thirst
• High blood pressure
• Anxiety/insomnia

Nutritional interaction
Thiamine deficiency impairs retention of intracellular potassium and may lead to
wasting through the kidneys. In refeeding syndrome, a shift towards anabolic processes
in the cells increases potassium uptake and requirement. Thiamine supplementation
may increase the demand for potassium and intracellular retention.

Possible intervention
• Consumption of 1-2L coconut water per day
• Increase consumption or other potassium rich foods
• Alternatively introduce supplement (citrate, chloride, bicarbonate) 500-
2000mg per day with taken with a meal

Test type Test Low High

Blood RBC potassium ✓

Blood Serum potassium (less sensitive) ✓

Copyright © 2022 Elliot Overton 80

 Riboflavin (vitamin B2)

Symptoms of deficiency
• Dry lips
• Glossitis (painful tongue)
• Cheilitis
• Sensitivity to light and/or conjunctivitis
• Seborrheic dermatitis or scaly rash on face
• Poor response to dietary fat
• Fatigue

Nutritional interaction
The active forms of thiamine and riboflavin both serve as cofactors for several
enzymes involved in energy metabolism. It is possible that the upregulation of enzyme
function with thiamine repletion may also increase demand for other cofactor
vitamins, including riboflavin. Thiamine supplementation was also shown to increase
riboflavin excretion through urine and may therefore warrant additional
supplementation.

Possible intervention
• Increased consumption of foods rich in riboflavin: liver, kidney, salmon, egg
yolk, red meats
• Riboflavin and /or riboflavin-5-phosphate supplementation 25-300mg

Test type Test Low High

Urine organic acids Glutaric acid (urine OAT) ✓

Adipic, ethylmalonic, sebacic acid (urine

Urine organic acids
OAT) ✓

Whole blood Whole blood riboflavin ✓

Copyright © 2022 Elliot Overton 81

 Niacin (vitamin B3)
Symptoms of deficiency
• Nonspecific pruritic rash
• Cheilitis or glossitis
• Depression/Anxiety/Fatigue
• Neuropathy
• Loss of smell or taste
• Chronic diarrhea
• Nausea/acid reflux

Nutritional interaction
The active forms of thiamine and riboflavin both serve as cofactors for several
enzymes involved in energy metabolism. It is possible that the upregulation of enzyme
function with thiamine repletion may also increase demand for other cofactor
vitamins, including riboflavin. Thiamine supplementation was also shown to increase
riboflavin excretion through urine and may therefore warrant additional
supplementation.

Possible intervention
• Niacinamide (300-2000mg per day) or Niacin at same dose
• [alternatively] Nicotinamide riboside (300-900mg per day)
• With niacin supplementation always monitor methylation status and
consider co-supplementation with trimethylglycine

Test type Test Low High

Red blood cell NADH:NADPH ratio ✓

Urine organic acids Kynurenic acid ✓

Urine organic acids Xanthurenic acid ✓

Plasma Tryptophan (possibly) ✓

Copyright © 2022 Elliot Overton 82

 Pantothenic Acid (vitamin B5)

Symptoms of deficiency
• Non-specific foot pain or burning feet
• Constipation or poor gut motility
• Fatigue
• Difficulty with foods high in fat
• Insomnia
• Neuropathy or poor cognition

Less is known about the prevalence or signs of this

deficiency due to a low amount of studies

Nutritional interaction
Pantothenic acid serves as a precursor for CoA, which is converted into acetyl-CoA.
Acetyl-CoA is involved in the Kreb’s cycle, an important step in energy metabolism.
Furthermore, it is also necessary building block for the neurotransmitter acetylcholine.
Enhancing cholinergic output, or alternative stimulating energy metabolism through
using high-doses of thiamine may increase the demand for pantothenic acid.

Possible intervention
• Pantethine (300-900mg per day
or

• Pantothenic acid or calcium D-pantothenate 500-1500mg per day

Test type Test Low High

Urine organic acids Pantothenic acid ✓

Plasma Pantothenic acid ✓

Copyright © 2022 Elliot Overton 83

 Pyridoxine (vitamin B6)

Symptoms of deficiency
• Dry lips
•• Glossitis (painful tongue)
•• Cheilitis
•• Sensitivity to light and/or conjunctivitis
•• Seborrheic dermatitis or scaly rash on face
•• Poor response to dietary fat
•• Fatigue
•

Nutritional interaction
Thiamine and pyridoxine play central roles in maintaining brain function, neurological
health, and neurotransmitter balance. Both vitamins are involved in the metabolism
and/or action of GABA, glutamate, and acetylcholine. Thiamine was also found to
allosterically regulate pyridoxal kinase, an enzyme involved in vitamin B6 metabolism.

Possible intervention
• Pyridoxal-5-phosphate supplement (25-100mg per day).

Blood Homocysteine in serum/plasma (possibly) ✓

Urine organic acids Kynurenic acid AND Xanthurenic acid ✓
Blood Pyridoxine (plasma) ✓
Alanine amino transferase (ALT) or
Blood liver enzymes Aspartate aminotransferase (AST) or ✓
Lactate dehydrogenase (LDH)

Urine organic acids Glycolic acid and oxalic acid (possibly) ✓

Blood Pyridoxine (plasma) ✓
RBC transaminase activity [EGOT after
Blood
addition of vitamin] ✓
Proline, glycine, serine,
Plasma amino acids
glutamine:glutamate ratio ✓

Copyright © 2022 Elliot Overton 84

 Biotin (vitamin B7)

Symptoms of deficiency
• Fatigue
• Low response to thiamine supplement
• Brittle hair and/or nails
• Hair loss
• Seborrheic dermatitis and dandruff
• Neuropathy (possibly)

Nutritional interaction
Thiamine and biotin serve as cofactors for enzymes involved in carbohydrate
metabolism (pyruvate dehydrogenase & pyruvate carboxylase, respectively) and are
also necessary for the breakdown of branched chain amino acids. Mild deficiency of
biotin was shown to caused a significant reduction in thiamine transport protein
expression (SLC19A3). Specific genetic defects in thiamine transporters have also
been shown to be responsive to combinations of high-dose biotin and thiamine
supplementation.

Possible intervention
• Increase biotin-rich foods including egg yolk and liver
or
• Biotin supplement 500mcg -15,000 mcg per day

Urine organic acids 3-hydroxyisovaleric acid ✓

3-hydroxypropionic & methylcitric acid (less

Urine organic acids
sensitive markers) ✓

Copyright © 2022 Elliot Overton 85

 Folate and Vitamin B12
Symptoms of deficiency
•• Low mood or poor motivation
•• Fatigue and lack of concentration
•• Megaloblastic anemia
•• Neuropathy or parasthesia
•• Elevated homocysteine
•• Histamine intolerance
•• Brainfog / poor brain function / anxiety
•• Emotional irritability/ mood disorder

Folate deficiency testing

Blood Serum folate ✓

Blood RBC folate ✓
Urine organic acids Formiminoglutamic acid [FIGlu] ✓
Blood Homocysteine ✓
Mean corpuscular haemoglobin (MCH) and
Blood
mean corpuscular volume (MCV) ✓

Possible intervention
• May require increased doses of methylfolate and/or follinic acid (300-
800mcg)

Copyright © 2022 Elliot Overton 86

 Vitamin B12 testing

Blood Serum B12 ✓

Blood Holotranscobalamin (active B12) ✓

Urine organic acids Methylmalonic acid ✓

Blood Homocysteine ✓

Mean corpuscular haemoglobin (MCH) and

Blood
mean corpuscular volume (MCV) ✓

Possible intervention
• May require supplementation with adenosyl/hydroxy/methylcobalamin (300-
1500mcg).

Nutritional interaction
Folate deficiency may impair the activation of thiamine to TPP through reduced
activity of the dihydrofolate reductase enzyme. Some evidence suggests that
unexplained chronic high blood folate levels in thiamine deficiency may return to
normal with thiamine repletion. Through increasing intracellular ATP concentrations
and anabolic cell processes, it is theoretically possible that thiamine exerts indirect
effects on methylation. Increases in methylation may increase folate and/or vitamin
B12 demand.

Copyright © 2022 Elliot Overton 87

 Choline

Symptoms of deficiency
Insufficiency of this nutrient is difficult to identify through
testing. However, some people report improvements in the
following symptoms:

• Pale stools / liver congestion

• Brain fog / poor brain function
• Emotional irritability/ mood disorder
• Non-alcoholic fatty liver disease / Non-alcoholic
steatohepatitis
• Intrahepatic cholestasis
• Elevated homocysteine
• Muscle pain

Nutritional interaction
Thiamine repletion may increase the production of acetylcholine, a
neurotransmitter which is composed partly made up of choline as a building block,
and enhance cholinergic nervous transmission

• Increase choline-rich foods including egg yolk and liver

• Supplemental phosphatidylcholine (1000-1500mg) and/or CDP choline (600-
1200mg)

Blood Alanine transaminase (ALT) ✓

Blood Aspartate aminotransferase (AST) ✓

Blood Alkaline phosphatase (ALP) ✓

Copyright © 2022 Elliot Overton 88

 Molybdenum
Symptoms of deficiency
Insufficiency of this nutrient is difficult to identify
through testing. However, symptoms of deficiency can
present in the following way:

• Flushing
• Tachycardia (fast heart rate)
• Wheezing, hives
• Dizziness, headache
• Anxiety, sweating
• Diarrhoea, tingling
• Sulfur body odour or flatulence
• Intolerance of sulfur containing vegetables

Nutritional interaction
The disulfide derivatives provide extra sulfur molecules to the body, which may place
an increased demand of sulfoxidation. It is possible that this enhances endogenous
generation of sulfite, which needs to be metabolized by the molybdenum-dependent
enzyme sulfite oxidase. Furthermore, in some individuals thiamine derivatives may
serve as substrates for sulfate-reducing bacteria in the intestine, which can produce
hydrogen sulfide (which is later converted into sulfite).
Anecdotally, many people witness improvement in side effects when supplementing
molybdenum alongside thiamine. This is most common with disulfide derivatives of
thiamine (TTFD and sulbutiamine) possibly due to the increased intake of sulfur
groups found within the structure of these forms.

Possible intervention
• Recommended molybdenum glycinate or sodium molybdate at a dose
between 250-2000mcg if necessary.

Blood Uric acid (possibly) ✓

Hair tissue mineral
analysis
Molybdenum ✓
Urine organic acids Sulfite:sulfate ratio ✓

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 Lipoic acid
Symptoms of deficiency
Insufficiency of this nutrient is difficult to identify since it can
be synthesised endogenously.

• Neuropathy
• Blood glucose fluctuations
• Fatigue
• Burning feet / paraesthesia
• Brain fog/lack of concentration

Nutritional interaction
The active forms of thiamine (TPP) and lipoic acid both serve as cofactors for several
enzymes involved in energy metabolism and amino acid metabolism. It is possible that
the upregulation of enzyme function with thiamine repletion may also increase demand
for other cofactor nutrients, including lipoic acid.
Both nutrients have been shown to exert synergistic effects on neurological function and
in nerve damage. In thiamine deficiency, one study shown that lipoic acid exerted toxic
effects, and this was reversed by the coadministration of thiamine.

Possible intervention
• Recommended form: R-Lipoic acid dosed between 300-600mg

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 Symptoms of deficiency
This is most common with disulfide derivatives of thiamine (TTFD).
Insufficiency of this nutrient can produce a wide variety of
symptoms. However, after glutathione administration some people
report improvements in the following symptoms:

• Fatigue and muscle weakness/pains

• Unrefreshing sleep / feeling of “sluggishness”
• Headache
• Poor concentration
• Neuropathy
• Brain fog

Possible intervention
• Supplementing with precursors NAC (600-1200mg) or NACET (100-
200mg), glycine (2000-5000mg)
• Liposomal glutathione (500-2000mg) or S-acetyl-glutathione (500-
2000mg)

✓
✓
✓

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 Nutritional interaction
Disulfide derivatives and benfotiamine have been shown to enhance the
production and turnover of intracellular glutathione (alongside other endogenous
antioxidants), possibly through enhancement of the pentose-phosphate-pathway.
The metabolism of disulfide derivatives may temporarily increase the oxidation of
reduced glutathione (GSH). Individuals with poor GSH status may therefore
benefit from supplemental glutathione.
Furthermore, in individuals with long-standing thiamine deficiency, thiamine
repletion may enhance detoxification processes and increase the demand for
glutathione. Anecdotally, many people witness improvement in side effects when
supplementing glutathione alongside thiamine (must be taken on an empty
stomach, at least one hour from TTFD or sulbutiamine). This is not important with
benfotiamine or thiamine HCL) Insufficiency of this nutrient can produce a wide
variety of symptoms. However, after glutathione administration some people
report improvements in the following symptoms:

Next section overview

The following section includes a list of common biomarkers provides information on

what the results may mean from a nutritional perspective. The type of tests
included are:

• Comprehensive blood count (CBC)

• Comprehensive metabolic panel

• Other markers on a blood panel

• Urine organic acids

• Other common markers in urine

• Plasma amino acids

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 Testing interpretation for
bloodwork
Comprehensive blood count
Mean corpuscular volume (MCV)
• If elevated above range, consider folate & B12 and cross-reference with folate & vitamin
B12 labs.
• If low: Consider iron, riboflavin or vitamin B6 deficiency

Mean corpuscular hemoglobin (MCH)

• If elevated above range, consider folate & B12 and cross-reference with folate & vitamin
B12 labs.
• If low: Consider iron, riboflavin or vitamin B6 deficiency

Mean hemoglobin concentration (MCHC)

• If elevated above range, consider folate & B12 and cross-reference with folate & vitamin
B12 labs.
• If low: Consider iron, riboflavin or vitamin B6 deficiency

Red cell distribution width (RDW)

• If elevated above range, consider iron deficiency and/or folate & B12 and crossreference
with other labs.

Red blood cell count

• If below range, consider iron-deficiency and/or vitamin B6 and/or folate & B12anemia

Hemoglobin
• If below range, consider iron-deficiency and/or vitamin B6 and/or folate & B12anemia. If
high, consider iron overload

Hematocrit
• If below range, consider iron-deficiency and/or vitamin B6 and/or folate & B12anemia. If
high, consider iron overload

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 Comprehensive metabolic panel

Alanine transaminase (ALT)

• Elevated liver enzymes ALT, AST, ALP: Consider increased need for liver support,
potentially including methylation, glutathione, choline etc.
• If low, consider insufficiency of pyridoxine (vitamin B6)

Aspartate aminotransferase (AST)

• Elevated liver enzymes ALT, AST, ALP: Consider increased need for liver support,
potentially including methylation, glutathione, choline etc.
• If low, consider insufficiency of pyridoxine (vitamin B6)

Alkaline phosphatase (ALP)

• Elevated liver enzymes ALT, AST, ALP: Consider increased need for liver support,
potentially including methylation, glutathione, choline etc.
• If low, consider insufficiency of zinc

Gamma glutamyl transferase (GGT)

• If elevated, consider increased need for liver support, especially glutathione. Consider
possible iron overload.
• If low, consider insufficiency of vitamin B6 and/or zin

Serum potassium:
• If low (<3.8): Increased need for potassium. Increase potassium-rich foods, coconut water
consumption and consider supplementation with 500-2000mg per day. Cross-reference
with magnesium because magnesium is necessary for potassium retention. Consider
taurine supplementation to enhance potassium retention.

Ammonia
• If elevated, consider increased need for zinc and/or magnesium

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 Other common markers in blood

Homocysteine:
• If elevated (>8): Consider increased need folate and/or vitamin B12, and/or methyl donor
nutrients including choline and betaine. Cross reference with folate and vitamin B12
markers of insufficiency. Also consider increased need for B6.

• If low (<5): Consider increased need for glutathione and/or inorganic sulfate, which may
increase flux through the transulfuration pathway (suspected if 2-hydroxybutyric is
elevated). Possible need for supplementation with precursors NAC, glycine and/or
glutathione. Cross reference with other glutathione markers.

RBC & serum folate:

• RBC elevated : This is primarily non-methylated folate. Consider whether elevated
through supplementation, which is normal. May be elevated in chronic thiamine
deficiency and normalize later.

• RBC if low: Consider supplementation with non-methylated folate – follinic acid.

• Serum elevated : This is primarily methylfolate. Consider whether elevated through

supplementation, which is normal. May be elevated in chronic thiamine deficiency and
normalize later.

• Serum decreased: Consider supplementation with methylfolate. Assess genetics

(MTHFR etc).

RBC magnesium:
• If low (<4) Consider addition supplementation with 100-400mg. Use bioavailable forms
(malate, glycinate, taurate) or ReMag.

RBC potassium:
• If low (<90), increase potassium-rich foods, coconut water consumption and consider
supplementation with 500-2000mg per day. Cross-reference with magnesium because
magnesium is necessary for potassium retention. Consider taurine supplementation to
enhance potassium retention

Uric acid:
• If low: May indicate increased need for molybdenum. Cross reference with hair mineral
analysis (molybdenum low) and sulfite/sulfate ratio (high). Consider additional
molybdenum supplementation at 100-1000mcg per day

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 Plasma B6:

• If elevated significantly above range: This finding is common with B6 supplementation and is
sometimes found in thiamine deficiency (which may normalize with thiamine repletion).
Consider reducing/avoiding all supplemental B6.

• If low: Consider supplementation with P5P 25-100mg per day and re-testing after one
month

RBC glutathione (GSH):

• If low, consider oxidative stress and increased need for glutathione. Possible need for
supplementation with NAC, glycine and/or glutathione. Cross reference with 3-
hydroxybutyric acid (high), pyroglutamic acid (possibly high, indicating glycine need, or low),
and possibly GGT (elevated). Methylation panel recommended to assess plasma glycine,
homocysteine, cysteine & cystathionine

Testing interpretation for

urine
Urine organic acids
Recommended tests: NutrEval & Metabolomix (Genova Diagnostics or Organic
Acids Test (Great Plains Lab)

Methylmalonic acid
• If high: Increased need for vitamin B12. Consider adenosylcobalamin supplementation.

Formiminoglutamic acid (FIGLU) (functional folate status)

• If high: Increased need for folate. Consider follinic acid and/or methylfolate
supplementation.

Pyruvate
• If high: May be indicative of slow/inhibited pyruvate dehydrogenase activity, pyruvate
carboxylase activity, or Kreb’s/TCA cycle and/or mitochondrial dysfunction. This marker
often responds to increased doses of thiamine. Also consider increasing lipoic acid, niacin,
riboflavin, Coq10 and biotin doses.

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 Lactate
• If high: May be pyruvate dehydrogenase activity, pyruvate carboxylase activity, or
Kreb’s/TCA cycle and/or mitochondrial dysfunction. Consider increasing thiamine, lipoic
acid, niacin, Coq10 and/or biotin doses.

Glutaric, adipic, ethylmalonic, sebacic acids (fatty acid metabolism)

• If high: May be indicative of poor metabolism of lipids. May suggest increased need for
riboflavin and/or carnitine. Consider supplementation with riboflavin and/or carnitine.

Methylcitric and/or B-hydroxyisovaleric and/or B-hydroxyproprionic

acid
If high: Poor biotin status. Consider supplementation with biotin 500-10000mcg.

Pyroglutamic acid
• If high: Poor glycine status which is limiting glutathione production. Consider
supplementation with glycine at 5-10g per day, hydrolysed collagen, and cross-reference
with glutathione section.

• If low, it could mean there is as reduced production of glutathione.

3-hydroxybutyric acid

• If high: Increased flux through transulfuration (homocysteine → cysteine) due to increased

demand for inorganic sulfate / taurine / glutathione because of oxidative stress.
• Consider supplementing with glutathione, taurine, NAC and other glutathione precursors.
Epsom salts baths daily are also recommended.

Sulfite:Sulfate ratio
• If high: Increased need for molybdenum. Consider supplementing with molybdenum.
Epsom salts baths daily are also recommended.

Kynurenic acid

• If high including elevated xanthurenic acid: Vitamin B6 insufficiency is likely

• If high with low xanthurenic acid: May indicate increased need for niacin

Xanthurenic acid

• If high including elevatedkynurenic acid: Vitamin B6 insufficiency is likely

• If low withhighkynurenic acid: May indicate increased need for niacin

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