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Carbon Dioxide: The missing piece in a metabolic jigsaw puzzle

Our body’s capacity to produce energy is dependent on oxygen. Our cells  are capable of producing much more energy in the presence of oxygen compared to a non-aerobic state *. Approximately 90% of the oxygen in our cells is used for energy production (1). So how can we ensure the delivery of adequate oxygen to our cells?

When most people are out of breath, they tend to breathe faster and take bigger breaths. Both of these actions will offer a temporary release for the air-hunger sensation but will not improve cell oxygenation – at least not in the long run.

 

In order to grasp how erroneous the idea of air hunger equating lack of oxygen is, think of the following: During an asthma attack patients are advised to breathe through a brown bag. If they need more oxygen, why should they restrict their oxygen intake?

 

 

The two breath parameters: Frequency & volume

Most people take between 10 and 16 breaths per minute. The volume of air that we inhale is approximately 500 millilitres per breath . This translates to approximately 6 litres per minute. When increasing the frequency of breaths, the volume of air per breath is reduced and vice versa, keeping the total volume of air inhaled the same.

 

Strange as it may sound, the increase of air in the lungs is not what is required for better oxygenation of our cells. Inhalations allow the body to take oxygen in. Most of the time though, the body retains high oxygen saturation levels. By using an oxygen meter we can prove that our blood contains 95-99% of its total oxygen capacity most of the time. If our blood constantly contains good levels of oxygen, why do we “run out of breath” at the end of a strenuous workout or when walking quickly up stairs?

 

 

The role of carbon dioxide in oxygen transport

Carbon Dioxide** is a by-product of fat and carbohydrate metabolism (aerobic and anaerobic). It exists in the fresh air at concentrations of 0.036-0.041% (36-41ppm). At 1% (10,000 ppm) concentration it can cause sleepiness and between 7 – 10%*** suffocation.

In 1904 **** physiologist Christian Bohr discovered the Bohr effect. Based on the Bohr effect, haemoglobin in the blood requires Carbon Dioxide (CO2) in order to release Oxygen (2). Low levels of CO2 in the blood, increase the affinity of oxygen to haemoglobin, preventing it from moving to the cells.

 

So, while at high levels CO2 can be toxic (3), at low levels it can deprive our cells of oxygen (based of the Bohr effect). Which raises the question, “what is the optimal level of CO2”? Before answering this question we need to review one more function of CO2: its role to signal our need to inhale!

Our brain is responsible for the control of our breathing cycle. Receptors in the brain continuously monitor a number of blood markers to signal the need for the next inhalation (4). Among these, the most critical, marker, is the levels of CO2 in the blood (5). When the levels of CO2 reach our tolerance point we get the urge for the next inhalation. Those familiar with the sport of underwater diving are aware of this concept.

 

 

So in order to deliver oxygen to our cells efficiently we need to prolong our urge for the next inhalation (i.e. increase our tolerance to CO2) and not increase our body’s levels of CO2. The beneficial metabolic effects of temporary exposure to an elevated CO2 state has been demonstrated in scientific studies. In one study the application of CO2 to transcutaneous tissue led to the proliferation of  mitochondria, similar to the one observed during aerobic exercise (6).

 

 

It is worth pointing out that in most medical centres the saturation of oxygen (SpO2) in the blood is monitored regularly. Nonetheless, good levels of SpO2 in the blood do not equate good levels of SpO2 in the organs. Our ability to deliver oxygen to our cells is dependent on our tolerance to CO2.

A good reference book on this topic is: “Oxygen Advantage” by Patrick Mckeown. On the Youtube Oxygen Advantage channel you can find several exercises to improve your tolerance to CO2.

 

 

Fun fact

The concept of better delivery of oxygen to cells is also the reason for which some athletes train at high altitude. High-altitude training became popular after the 1968 Mexico Olympics. Mexico is located at 2,300 metres above sea level. During this Olympiad, many athletes surpassed their previous performances, which prompted coaches to question if the location, was conducive to athletic performance. At high altitude the oxygen is reduced. At a hypoxic (low in oxygen) environment, the body is forced to produce more red blood cells. More blood cells means more available vehicles to carry oxygen to the cells. However, soon after an athlete, returns to sea level, the number of red blood cells returns to normal levels.

 

 

Footnotes

* One molecule of glucose will produce two molecules of Adenosine Triphosphate (ATP – our body’s energy currency) in an anaerobic state, as opposed to thirty six molecules of ATP in an aerobic state.

** Carbon Dioxide, a natural-occurring product of metabolism, that should not to be confused with Carbon Monoxide, a flammable gas that does not occur naturally in the atmosphere.

*** In one study subjects were exposed to air containing 7-14% of CO2 for 10-20 mins. All subjects had a complete recovery of their physiology 10 mins after the end of the experiment (7).

**** That was 33 years before Han’s Krebs’ discovered the eponymous Krebs cycle.

 

References

  1. Bland, J., Costarella, L., Levin, B., Liska, D., Lukaczer, D., Schiltz, B. and Schmidt, M.A., 1999. Clinical nutrition: A functional approach. The Institute for Functional Medicine, Gig Harbor, Wash, USA.
  2. Bohr, C., Hasselbalch, K. and Krogh, A., 1904. Über einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensäurespannung des Blutes auf dessen Sauerstoffbindung übt. Acta Physiologica16(2), pp.402-412.
  3. Satish, U., Mendell, M.J., Shekhar, K., Hotchi, T., Sullivan, D., Streufert, S. and Fisk, W.J., 2012. Is CO2 an indoor pollutant? Direct effects of low-to-moderate CO2 concentrations on human decision-making performance. Environmental health perspectives120(12), p.1671.
  4. Huckstepp, R.T. and Dale, N., 2011. Redefining the components of central CO2 chemosensitivity–towards a better understanding of mechanism. The Journal of physiology589(23), pp.5561-5579.
  5. Cheung, S., 2010. Advanced environmental exercise physiology. Human Kinetics.
  6. Oe, K., Ueha, T., Sakai, Y., Niikura, T., Lee, S.Y., Koh, A., Hasegawa, T., Tanaka, M., Miwa, M. and Kurosaka, M., 2011. The effect of transcutaneous application of carbon dioxide (CO 2) on skeletal muscle. Biochemical and biophysical research communications407(1), pp.148-152.
  7. Sechzer, P.H., Egbert, L.D., Linde, H.W., Cooper, D.Y., Dripps, R.D. and Price, H.L., 1960. Effect of CO 2 inhalation on arterial pressure, ECG and plasma catecholamines and 17-OH corticosteroids in normal man. Journal of Applied Physiology15(3), pp.454-458.

 

How to detect vitamin B12 deficiency

Vitamin B12 is common and unfortunately one cannot rely on serum vitamin B12 to detect a deficiency. Vitamin B12 is carried in the blood by either of 2 proteins: haptocorrin and holotranscobalamin. While the majority of vitamin B12 is carried by haptocorrin, this vitamin B12 is considered inactive* [1]. A serum vitamin B12 test cannot differentiate between the active and inactive form and as a result while the level may appear healthy, the active form of vitamin B12 may be significantly low.

 

Which test is best to identify vitamin B12 deficiency?

The most direct why to detect vitamin B12 deficiency is to measure your active form of B12: holotranscobalamin. Biolab in UK offers that test.

If that test is not available to you, your 2nd best option is to measure your homocysteine levels. Homocysteine is a protein humans synthesise in their body and it’s considered one of the most significant biomarkers of cardiovascular health. Its production relies on the availability of vitamin B12, folate & protein.

source: PMID 16702348 [4]

As multiple other factors though affect the levels of Homocysteine, one cannot drive conclusive results for her vitamin B12 just knowing her homocysteine level.

 

 

Which symptoms indicate vitamin B12 deficiency?

Vitamin B12 plays a critical role in the methylation cycle [3] (which consists of the folate & methionine cycle). As a result any problems associated with methylation may be driven due to:

  1. low vitamin B12 intake (important for vegans and vegetarians)
  2. poor absorption (relevant for those with poor gastrointestinal function) [2] or
  3. compromised metabolism (possibly due to MTR & MTRR polymorphisms)

 

 

 

* due to the fact that haptocorrin receptors are found mainly in the liver.

 

  1. Morkbak, A.L., Poulsen, S.S. and Nexo, E., 2007. Haptocorrin in humans. Clinical Chemical Laboratory Medicine, 45(12), pp.1751-1759.
  2. Schjønsby, H., 1989. Vitamin B12 absorption and malabsorption. Gut, 30(12), p.1686.
  3. Miller, A., Korem, M., Almog, R. and Galboiz, Y., 2005. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. Journal of the neurological sciences, 233(1), pp.93-97.
  4. Refsum, H., Nurk, E., Smith, A.D., Ueland, P.M., Gjesdal, C.G., Bjelland, I., Tverdal, A., Tell, G.S., Nygård, O. and Vollset, S.E., 2006. The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. The Journal of nutrition, 136(6), pp.1731S-1740S.

Fasting Diet: progressions

This article is written with deep respect in the process of fasting and consciousness that the epigenetic effects of a Fasting Diet are far reaching (beyond the current scientific evidence). Yet fasting in my opinion is something we all need to be comfortable with. There are many disputes on what the healthiest diet is, with advocates of the different diet-types often trying to strengthen their view using ethnological and ancestral data. It is (I hope) clear to everyone though that our ancestors had to survive periods of fasting independent of whether these were caused due to lack of game or disaster in the crops.

My Journey with the Fasting Diet

I have been following one of the Fasting Diet progressions described bellow since September 2009. At the time (after reading my first book on nutrition called: Food Governs your Destiny) I set 3 2hour slots in the day during which I allowed myself to eat. Outside these windows I would consume only liquids. I stayed on the diet for 6 months, during which I:

👉🏻 reduced my waist circumference from 34 to 29 inches.

👉🏻 lost 7.5 kilos.

👉🏻 achieved mental clarity I have never experienced before.

During a big part of these 6 months I was vegetarian.

In 2016 I decided that as a way of monitoring my metabolism I would like to measure the production of ketones in my body. Between October 2016 and February 2017 I monitored my Blood Glucose (BG) and Ketone Bodies (KB) – beta-hydroxybutyric acid on a daily basis. Monitoring can be useful:

👉🏻 as feedback for one’s response to food / exercise.

👉🏻 for compliance when BG & KB targets are set.

During this period there were weeks of following a vegetarian diet but most days I consumed meat.

Fast Diet: Progressions

Bellow I share what I consider to be a natural progression. However not everyone starts with a: 3 meals and 2 snacks diet and neither do they all have the same tolerance to the changes each step requires. I imagine you have not been eating the same way all your life. Erring on the safe side by staying on each stage longer is not a bad idea. You have a lifetime to evolve your diet further.

⏱ Time Restrict your Eating

I think that the 16-8h type-diets are easy for most to adopt and provide a great initiation to fasting. In the 16-8h diet: one eats during an 8 hour window and fasts the rest of the day (16hours). The easiest way to get into it is to prolong the overnight fast. Assuming one sleeps for 8 hours and stops eating 4 hours prior to going to bed, she / he can achieve the 16/8h fast by eating 4 hours after waking up. If the idea still feels daunting here are a few tips to ease your way into it:

👉🏻 Start with a 12-12h diet and gradually increase the fasting window. The danger hear is not to be consistent. Decide which window schedule suits you and stick to it for at least 1 week before increasing the fasting phase.

👉🏻 Take days off if you find the idea of doing it daily suffocating. However have the days scheduled before hand and do not change them. Say you have Thursday & Sunday off. Sunday comes and you feel you need a day off go back to your old schedule. Until you have 4 consecutive weeks with 5 days per week on your “Time Restricted Eating” schedule do not assume you are ready to proceed.

🌞 Eat while the Sun is up

While I acknowledge that many people working in offices have more physically active evenings than mornings; the body’s biological clock (while adaptive) is not necessarily flipped upside down because of your client’s deadlines. Neither your sleeping time can accommodate all the digestion you wish just because your gym class finishes at 22:00. As a next step to a “Time Restricted Eating” I consider to be the swift of the eating window earlier in the day. How early is early? – you decide. My suggestion is to finish eating prior to the sunset and ideally by midday. Actions that helped me with this transition:

👉🏻 Exercise earlier in the day.

👉🏻 Make sure the quality of my sleep is not compromised. Supplements as well as breathing practices can support a good night sleep. Initially prolonged fasts cans lead to elevated cortisol levels which will mess up with sleep. Poor sleep leads to tiredness and erratic appetite the next day.

⏰ Set your Eating Times

That stage could also be called: Stop snaking. Most of us (living a western lifestyle) have constant access to food and numerous stressors during our day. The combination of the two in many cases lead to binging / snaking. Whether you call it comfort food or not every extra meal (and by meal let’s call anything containing more than 20 calories) requires the activation of the pancreas and the subsequent release of insulin. Insulin is a hormone with multiple roles in our biochemistry other than food metabolism. With that in mind I don’t find strange that hormonal imbalances are common in those with erratic eating patterns.

If one attempts to “Set her Eating Times” while she is eating during day time only, I expect this transition not to be a big challenge. On the other hand shifting from a 16-8h fast to a “Set Eating Times” schedule can be a bigger step.

Setting the times when someone eats is personal and can be scheduled around her lifestyle. My suggestion is to schedule no more than 3 meals a day and if for whatever reason a meal is lost not to be replaced.

☝🏻 Eat Once a Day

If you have been following the progression described above I would be surprised if you are eating more than twice a day. Eating once can be something you want to try occasionally based on your energy expenditure & mood. If you balance between 1 and 2 meals per day keeping the 2nd meal light (i.e. snack) can be a way of staying on track and avoiding the slippery slop of getting back to old patterns.

😶 Eat only When Hungry & As much as you Need

Even when eating once a day I still find hard not to overeat. I consider our relationship with food complex and the addictive aspect of it multidimensional. We can be addicted to:

👉🏻 certain foods.

👉🏻 the sensation of fullness.

Whatever the addiction is it will always manifest to emotions which make it hard to break loose of. To that extent I would like to clarify that:

“I consider eating one of the big joys of life & fasting can only enhance this sensation.”

Fasting works as a challenge for the body. This doesn’t mean it makes it any weaker. In the same way that you would not assume a runner to be doing harm to her body just because her legs are weak at the end of a training session, don’t be afraid of fasting.

Fast Diet: Considerations

Most people when considering fasting are worried about their energy levels and weight management. Those that depend on constant food consumption to maintain their energy levels (i.e. T2D) are the ones that would benefit the most from fasting in my opinion but may require to progress slowly. As for weight management exercise and caloric intake when adjusted accordingly can help achieve the admired goal.

🔑  Things to consider

👉🏻 Always keep your (AME ) Appetite, Mood and Energy levels in check. If one of them is not under control adjustments may be necessary. In most cases soon after one gets out of control the other 2 follow.

👉🏻 Our life changes constantly and so will our mood, circadian cycle, appetite, needs for nutrients etc. I hope this article works as a road map not an itinerary.

👉🏻 Food composition can affect your Blood Glucose and consequently your fasting phases. Fibre, fat, protein can slow down your meals’ metabolism which is necessary initially.

👉🏻 Metabolism is complex and its efficiency depends on many factors including: oxygen availability & insulin sensitivity. The Wim Hof Method can be very useful towards improving metabolic efficiency and supporting a fasting practice.

Things to consume while fasting

In order to maintain the calories low during fasting my suggestion is to limit your liquid intake to coffee & teas. As stimulants can play havoc in some people’s metabolism & appetite they should avoid the caffeinated drinks all together. I have been consuming them freely. Two things that can help a lot in extending your fasting periods are:
👉🏻 Water – in particular fizzy. I think it is easier if one takes sips during the day aiming for 1-3 litters as opposed to drinking 3 glasses when filling peckish.

👉🏻 Magnesium Citrate powder (I like the one from Designers for Health). Its sweet taste can help deal with a sweet tooth while the Magnesium supports the adrenals & promotes gut mobility.

👉🏻 Brushing teeth after eating. Making sure mouth hygiene is in check can help in 2 ways: 1. some associate a clean mouth with the end of eating 2. food leftovers will stop triggering taste buds receptors.

 

Feel free to let me know of aids you have found useful during fasting and I can include them in the list.