Why to be sceptical of reference ranges and look deeper?

When a lab is setting up a new blood test, they can use the manufacturer’s range based on..

1) Reagents provided (pre-made solutions)

2) Published reference ranges

3) Locally established reference ranges as the baseline. 

They then confirm these reference ranges using a minimum sample population of 20-25 patient samples to confirm that these reference ranges correspond to the local population that the testing laboratory will be conducting this blood test on. 

Limitation #1: We live in a very heterogeneous society, particularly in major Australian cities, thus the ranges can be skewed to a demographic that you may not be (minority populations and mixed ethnicity)

Limitation #2: Unhealthy user bias. This is where unhealthy people are typically biased to perform a certain behaviour (e.g. go to the Doctor and get their blood tested).

This attracts sicker more unhealthy people to get their blood tested, thus the sample that confirms these ranges can be confounded.

There are comparatively very few healthy patients who are just curious to check their bloods and will be a part of this sample.

This skews the data towards a reference range that represents poorer health.

If there are no published reference ranges, a population of ~120 patient samples are required from the local ‘healthy’ population. 

Basic statistics are then applied and the 95% percentile is then used to establish the normal population.

Limitation #3: It is important to note that this means that 5% of the population will fall outside of this normal reference range.

Strength #1: This is good because they will control for major risk factors such as smoking, obesity and disease.

However, we all observe that the average ‘healthy’ population can often be unhealthy in many ways (overfat, GI issues, micronutrient deficiencies, poor mental health, low exercise frequency).

This again skews the data in a way that you may not like to be compared against.

The Ideal World

In an ideal world, reference ranges would be sub-categorised based on different levels of health status, lean body mass, strength levels and overall wellbeing. This would allow the patient and Doctor to negotiate on who they should be compared against.

An overweight 50 year old with diabetes probably doesn’t need to be compared to a 25 year old athlete.

Yet the reference ranges are based on both these people.

An alternative solution would be comparing the 50-year-old to a healthier standard deviation. Then you would aim to slowly move him to the ideal health status one standard deviation at a time.

On the other hand, the athlete who wants to improve and maintain would be compared to his respective cohort, not to the average ‘healthy’ population which is not who he aspires to be.

The Solution

Now, this obviously doesn’t exist in traditional medicine, but it does exist!

Where?

In the hands of health professionals who…

1. Spends time reading modern literature to stay up to date on what is ideal and optimal.
2. They align with the value that being average is not ideal.
3. They have the value and skillset to maximise the health, wellness and performance of their clients.
4. Publically and privately admit when they’re wrong and have learnt something new.
5. Is not emotional or dogmatic about views towards certain health behaviours.
6. Can argue the opposite perspective to their own belief.

These are traits of a coach, health professional or Doctor you want to look for if you want to be more than average.

Have healthy scepticism and look deeper into your health with someone who understands that you need to comprehensively look at the entire human.

Diving Deeper Into Reference Ranges

Location

The way that reference ranges are determined also needs to be kept in mind when travelling around different hospitals or clinics that use different pathology providers – reference ranges might be similar amongst testing laboratories but there will be some subtle differences. There are also different testing methods used which may affect the reference ranges.

Example: Mean Cell Volume (MCV)

The mean cell volume, or MCV, is a red blood cell indices that measures the average volume of a red blood cell.

Values obtained outside the normal range can be indicative of thalassemia, anaemia, vitamin deficiency, or alcoholism. Depending on the testing lab, the reference range may be:

• 79 – 93 fL (http://perinatology.com/Reference/Reference%20Ranges/Mean%20corpuscular%20volume.htm)
• 80 – 96 fL (https://emedicine.medscape.com/article/2085770-overview)
• 80 – 100 fL (https://www.mydr.com.au/tests-investigations/full-blood-count-fbc)

If you’re moving areas be considerate that your reference range may be different to your new location. 

Practical Examples: TSH & PSA

In practice, there are no rigid limits demarcating the diseased population from the healthy.

The normal reference range for TSH is 0.4 – 4.0 mU/L.

However, if a patient presents with a result of 4.05, you wouldn’t immediately scream ‘hypothyroidism’.

You would take the result in light of the clinical picture you have developed by looking at all the other symptoms a patient presents with and then make an informed decision.

Furthermore, you would acknowledge that most clinical symptoms, modern data and clinicians will generally agree that TSH >2.0 is often problematic, particularly for females trying to conceive.

In practice, there is quite a bit of overlap in values between normal and diseased pathology results.

The prostate-specific antigen (PSA) is an example of this:

This is the scenario that we are frequently left with. If we have a cutoff at E, we pick up everyone with the disease – everyone is a true positive. But we’re also missing a lot of patients whose results may be lower and fall into the normal reference range. 

Move it to C, we get more true positives, but we’re also getting a number of false positives.

If we move the cutoff to A, we pick up everyone with prostate cancer. We also pick up nodular hyperplasia and prostatitis and those patients have to undergo a biopsy, but it’s better to pick up all patients with cancer than miss a few and have to provide palliative care later when the disease is too advanced.

This is wonderfully objective and contextual. I don’t know if Doctors < the 2010s were taught this type of mentality, but modern Doctors coming up now I am excited about.

Practical Example: Creatinine

Creatinine is a waste product produced by muscle and it is produced at a fairly constant level.

It is not absorbed or secreted and must be excreted by the kidney.

A high level in the blood could indicate kidney dysfunction.

I often see this along with Urea high in my clients because almost all of them consistently weight train 3-5x p/w and consume a high protein diet.

The context of this lends itself to a different interpretation.

Creatinine Reference Ranges

Male: 60 – 120 umol/L

Female: 45 – 90 umol/L

7 – 11-year-olds: 29 – 65 umol/L

If an asymptomatic young female patient presents with a creatinine of 130 umol/L, this could mean she has renal disease…BUT…there are clear issues with this assumption. 

Morjorie started bodybuilding at the age of 72. This picture was taken when she was 86.

If she turned up to your clinic in a T-shirt or jumper, your assumption would be that she is your typical geriatric patient.

A creatinine result of 130 umol/L would start you organising immediate treatment for kidney dysfunction.

However, because she works out frequently, this would be a normal result for her.

While she is an outlier, this result would be normal for many females who weight train consistently (they are not outliers).

Blood Test Confounding Factors

The Mistake Of Looking At One Blood Test

Reference ranges are only a guide and you need to compare these results to previous results.

Thus we want to look at TRENDS over time not solely rely on snapshots of moments in time.

If a result does not fit with the clinical picture you have come up with based on symptoms and the clinical picture, repeat the test with a fresh sample.

There can be several reasons for an unexplained result. This could be because of:

• Pre-analytical, occurring outside the laboratory, e.g. the wrong specimen being collected, mislabelling, incorrect preservation, etc.
• Analytical, occurring within the laboratory, e.g. human or instrumental error: precision/accuracy; lipaemia; haemolysis.
• Post-analytical, whereby a correct result is generated but is incorrectly recorded in the patient’s record, e.g. because of a transcription error.

Most Doctors coming up in the last 5-10 years are taught that just because the patient’s result falls into the acceptable reference range, this may be an abnormal result for them.

But there are many old school traditionally minded Doctors who unfortunately haven’t stayed up to date on the changes and advances in thinking and science.

Please be patient and empathetic with them, some people are just stuck in the mud and don’t even know it.

For more education on maximising health, wellness and performance follow me on Instagram, Facebook & YouTube or see my coaching services here to get into the best health of your life.

P.S. Please note this is how Australian health practitioners are taught this may not representative of other countries.

The post The Dangers of “Normal” Blood Test Ranges: Optimal vs Normal & How Blood Test Ranges Are Made appeared first on Strength of Saad.

Serum B12 blood test is pretty at detecting deficiency. Be skeptical if your Doctor sais ‘your B12 is in range you’re normal’, yet you’re experiencing adverse symptoms (fatigue, memory problems, weakness, dizziness, infertility) or just want to be proactive with your health.

Who Should Be Concerned? B12 Deficiency High-Risk Groups:

• Plant-based eaters.
• Elderly (less intrinsic factor produced as you age which absorbs B12).
• Gut issues (e.g. chrons, IBD.)
• Binge alcohol drinkers.
• Diabetics or athletes taking metformin.

Should all ideally get holo-transcobalamin (active B12) and/or methylmalonic acid and homocysteine testing.

“Serum B12 levels are wrong; the lower limit of the normal range should be 300 pg/ml and not 170 pg/ml or 200 pg/ml. Further, it has been concluded that the serum B12 is too non-specific to be a reliable guide of B12 status; instead, we should look to the serum MMA level.”

‘I take supplements so I’m fine…’

1. Not necessarily, malabsorption occurs frequently in the elderly, those with gut bacterial overgrowths, low stomach acid, and nutrient deficiencies. Just because you get enough dietarily doesn’t mean you’re meaningfully improving your B12 status.
2. “Supplements, fortified food, and beverages normally contain the less efficient cyanocobalamin form of vitamin B12, which when it enters the bloodstream must be converted to methylcobalamin, the only form of vitamin B12 that has a methyl donor that is required to neutralise homocysteine. It takes 4–9 weeks for this conversion to take place assuming there are no disruptions by genetic factors, age-related problems, and metabolic obstacles that may be present.”
3. “Furthermore, research suggests that vitamin B12 that is not dissolved in the mouth will not (up to 88 %) be absorbed, due to the lack of R-binder mostly obtained from saliva, which is required to start the absorption process. The aforementioned study indicates that supplementation with cyanocobalamin can be poorly absorbed, which will have little or no effect on raising vitamin B12 levels.”

Methylcobalamin lozenge supplements dissolved in the mouth are an ideal replacement.

“Measurement of homocysteine and/or methylmalonic acid should be used to confirm deficiency in asymptomatic high-risk patients with low normal levels of vitamin B(12).”

“ The usual dietary source of vitamin B₁₂ is animal products and those who choose to omit or restrict these products are destined to become vitamin B₁₂ deficient.”

Conclusion

Let’s be very careful about removing foods/food groups from our diet. Most health professionals struggle to understand the complex biochemistry of nutrition and supplementation let alone the average person.

You can severely fuck yourself by naively supplementing and removing food groups. A google search and conversation with your pharmacist are not sufficient. You should be studying in the area and/or work with someone who is and does understand this to minimise the eventual risks of nutrient deficiencies.

For more education on optimising health, wellness and performance follow me on Instagram, Facebook & YouTube or see my coaching services here.

References

• Diagnosis of cobalamin deficiency: the old and the new – PubMed
• Update on vitamin B12 deficiency – PubMedVitamin B(12) (cobalamin) deficiency is a common cause of megaloblastic anemia, a variety of neuropsychiatric symptoms…pubmed.ncbi.nlm.nih.gov
• Vitamin B12 DeficiencyVitamin B12 (cobalamin) is a water-soluble vitamin that is derived from animal products such as red meat, dairy, and
• Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and…Edit descriptioncore.ac.uk

The post How To Detect A B12 Deficiency appeared first on Strength of Saad.

IF I HEAR ANOTHER DOC SAY YOUR BLOOD TEST IS NORMAL

Read until the end if you want to know how to identify iron deficiency anaemia even though your bloods are in normal ranges.

I’ve heard this story too many times…

Client does blood tests I ask for… 

Everything is in range and ‘normal’ according to the Doc. 

Yet the client is suffering from a litany of symptoms. 

Antipsychotic, antidepressant or steroid creams may be prescribed with minimal if any effort to get to the underlying issue.

Worst case, this is malpractice. Best case, this is ignorance and indifference.

Here’s how I could tell this iron panel wasn’t normal in 10 seconds…

Transferrin is like a boat that transports iron throughout the body. Elevation of transferrin is an indication the liver is signalling to make more transferrin. Above is 3.3 nearly out of the range (optimal: low-mid 2.0’s).

We can see here the body is trying to make more of these transferrin boats. 

Why is it doing that? 

High probability: because it doesn’t have enough iron.

We’re more confident in this theory once we see transferrin saturation is 13%. It looks ‘in range’ but it’s actually quite low. These boats are almost empty (not much iron in them). Transferrin saturation is an indication of how loaded the transferrin boats are WITH IRON. We want this in the mid-high 20’s%.

This show’s us the client has iron and/or copper deficiency which is consistent with symptoms of low energy levels and fatigue.

Why did I mention copper? 

Ceruloplasmin is a protein/ferroxidase enzyme made in the liver that loads iron into the boat (transferrin) to be transported through the body. Ceruloplasmin stores and carries the majority of the bodies serum copper stores. So if you have a copper deficiency you can’t load iron for transport efficiently. Low copper → low ceruloplasmin → iron transport is screwed.

By copper and ceruloplasmin testing, we can determine if the client has a copper and/or iron deficiency and implement an appropriate nutrition strategy instead of indiscriminately giving IRON SUPPLEMENTATION!! (which many health professionals do).

Ceruloplasmin

Most doctors won’t get this tested. But it is important and helps complete the picture of what intervention we should prescribe to the client. The cuproenzymes, superoxide dismutase and ceruloplasmin, are known to have antioxidant properties.

It should also be noted that if you see low ceruloplasmin (0.01–0.2 g/L) there could be other nutrient co-factor deficiencies at play. Ceruloplasmin depends on magnesium, Vitamin A, Vitamin C and which has the capacity to oxidize ferrous iron (Fe2+) to ferric iron (Fe3+), which can be loaded onto the iron-transport protein, transferrin (see Morley Robbins for more).

Identifying an iron deficiency is nuanced and not as simple as observing if an iron panel is ‘in range’. It is dependent on other tests to verify a pathology, help people out of debilitating symptoms and improve their quality of life.

I don’t think coaches like me should know more about the nuances of biochemistry, bloodwork and nutrition than a GP. 

But we force ourselves to because we see the flaw’s in the medical system and want to help people avoid being sick and proactively improve quality of life, health and wellbeing.

If you need guidance through optimising your health, wellness and performance contact me here or on my Instagram.

The post Your Blood Test Is Not Normal Part 1 – Iron | How You Could Be Anemic & Not Know It appeared first on Strength of Saad.

This is from a client who lost 10kg and got very lean (<40mm 9 site skinfolds and <8% body fat).

Lower T with very low body fat is one reason we see:

• Infertility (lower semen production + amenorrhea).
• Depression.
• Almost no libido.
• Sleep quality problems.
• Low energy, apathy and fatigue.

It is normal and expected to see testosterone plummet in response to a prolonged energy deficit with very low body fat levels. As you can see after 6 months of returning back to maintenance, gaining muscle and some fat, total and free T levels normalise. 

Testosterone, free testosterone and sex hormone-binding globulin (SHBG) are different forms of T in the bloodstream.

Bound Testosterone

T is bound to SHBG and albumin. These are proteins that bind and transport T through the body in a mostly inactive state (it can’t exert much, if any effect upon the body).

Unbound Testosterone 

~1–3% of the T in the body is ‘free’ which refers to its unbound state not attached to any proteins. In this unbound state it is biologically active and can bind to receptors.

Free T is arguably the most important number, not total T, because free T is what’s bioavailable and what going to bind to the AR receptor to exert its androgenic effects of the synthesis of tissue, energy levels, libido etc.

Total testosterone on a blood test is the sum of all the testosterone in your blood (bound and unbound).

A 40% energy deficit (30% dietary restriction + 10% increase in physical activity above energy requirements) resulted in significant decreases in circulating T despite a high percentage of caloric intake being from protein.

Luteinizing Hormone

If you’re concerned about your T levels you also want to get your luteinizing hormone (LH) checked. LH is known for causing the ovaries to release an egg. So male’s don’t typically care about it and Doctors don’t typically look at it in males. But LH is the signal for the testes to make more T.

Caloric deficits have been shown to significantly reduce LH pulse frequency and amplitude during waking hours and increase at night in women. Another study showed LH pulsatility is harmed during an energy deficit in women.

Nutritional Co-Factors 

Co-factors needed for testosterone metabolism include zinc and calcium to help bind SHBG.

A zinc ion is used on the conformation of the SHBG peptide chain and a calcium ion is needed to link what’s called a dimer (two identical molecules linked) together, keep it stable and improve steroid-binding activity. 

Often missing from the conversation of biochemistry is nutritional co-factors. So I wanted to highlight how deficiencies have the mechanistic probability to exert negative effects on testosterone. We now begin to see evidence of micronutrients like magnesium improving testosterone.

Final Thoughts & Practical Takeaway’s

• Manging nutritional deficiencies becomes paramount during an energy deficit.
• There is probably evidence that intaking optimal micronutrients (zinc, calcium, magnesium) before embarking on an energy deficit may improve one’s physiological response to the deficit.
• Low energy availability clearly has detrimental effects on physiology and the endocrine system. Though these effects are largely transient.

The post How Testosterone Plummets During A Caloric Deficit appeared first on Strength of Saad.

S-Adenosyl Methionine (SAM) is a compound found in nearly all tissues in the body that plays a critical role in breaking down catecholamines (neurotransmitters/stress hormones).

You need B-vitamins and magnesium to generate enough SAM. Thus if we are deficient in any of these we undermine our ability to degrade stress hormones that can keep us jacked up for longer.

If you’ve noticed over the years you’re more sensitive to anxiety and respond poorly to stress by taking a long time to calm down, it may be because of a B-vitamin/magnesium deficiency.

As you can see in the diagram ‘MAO’ and ‘COMT’ are enzymes involved in dopamine, norepinephrine and epinephrine metabolism. When we experience acute or chronic stress COMT and MAO break down these hormones so they don’t build up for too long. But these enzymes need nutrients we get from our food like meat (clams, liver) and green leafy vegetables/pumpkin seeds. Let’s be honest, most people don’t get enough and are nutrient deficient.

• NAD needs B3.
• FAD needs B2.
• SAM needs B12, zinc, magnesium.

If you can’t make SAM due to not having enough of its nutritional cofactors you will put pressure on other pathways like MAO and COMT and use a lot of B-vitamins in the process to compensate.

When there is a nutrient deficiency it’s like a road that becomes blocked, the traffic has to be distributed elsewhere. This causes traffic to build up (other nutritional resources get depleted) and car accidents are more likely to happen (adverse symptom, stress and illness).

Some people are naturally NOT good under high-stress situations and take a long time to calm down into a parasympathetic state. This is one probable common nutritional biochemical explanation why.

But let’s discuss and summarise some additional explanations…

#1 Sufficient Nutrient Cofactor Support To Support COMT/MAO Pathways

• There are physiological reasons why some people may be predisposed to being able to handle stress and manage the surge of catecholamines like adrenalin. 
• When we have excess dopamine, noradrenaline or adrenaline COMT is the enzyme that degrades catecholamines. But COMT is depdendent on SAM and Mg. We need B3, B2, B9 and B12 to make SAM. If we are deficient in these B-vitamins and Mg we’re gonna have a really bad time at managing stress and getting into a parasympathetic state.
• If you do not have adequate SAM resources you won’t be able to offload and metabolise the build of these catecholamines during high-stress situations.

#2 Fast Running COMT/MAO 

• Whether you’re a fighter or emergency responder you need to be able to stay calm under high sympathetic activity and stress.
• Some people have fast MAO/COMPT which means they will metabolise these neurotransmitters like dopamine and catecholamines really quickly.
• They may have a lower mood/temperament.
• Thus giving them the co-factors the COMPT/MAO may be accelerating the offload of these neurotransmitters even further.
• This explains how giving someone magnesium and B-vitamins can make people feel worse as it lowers mood, anxiety and even depression.
• It may result in dopamine being metabolised really quickly thus they may struggle more than others to seek things out (reward and motivation)
• Fast COMT/MAO metabolisers by default may have lower mood/temperament.
• So giving these people more co-factors like B-vitamins and Mg may be the last thing you want to do because it could worsen mood and trigger apathy and lower motivation through enhancing the breakdown of dopamine, adrenalin etc. 

#3 Slow Running COMT/MAO

• This is the opposite of the above. 
• It’s analogous to choking the funnel for catecholamines and neurotransmitters to be metabolised. 
• The COMT/MAO enzymes are just running too slow.
• In these cases giving these types of people, more of the co-factors for SAM (B-Vitamins & Mg) may help that sluggish enzyme normalise.
• These people usually respond the most favourably to supplementation.

As you can see, indiscriminate supplementation without considerations of biochemistry can make some people worse.

Plant-based eaters are probable to be deficient in B-vitamins. Meat only eaters are probable to be deficient in magnesium with 50% of the US population not meeting adequate intake levels.

Magnesium and B-vitamins have radical effects on transforming someone’s ability to manage stress. It’s a good idea to pay attention to them.

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The post Reducing Stress & Anxiety with B-Vitamins & Magnesium appeared first on Strength of Saad.