CO2 is a product of oxidative metabolism, as a result of the body metabolizing carbohydrates and fats to produce energy in the presence of oxygen. When oxygen is not present, carbohydrates are converted to lactate via anaerobic glycolysis. In some conditions, glucose is converted to lactate even in the presence of oxygen, as in the case of diabetes and cancer for example.
Carbon dioxide (CO2), produced in the cells, helps oxygenate tissue (Bohr effect), preserves stem cells, lowers glutamate and antagonizes NMDA (preventing too much excitation) (1, 2), increases the synthesis of new mitochondrial (increase in PGC-1a) (3), causes vasodilation (4), prevents edema (by antagonizing lactic acid), eliminates ammonia (5), increases the efficiency of oxidative metabolism, inhibits the glycation of proteins, scavenges peroxynitrite (by inhibiting xanthine oxidase (6)) and hydrogen peroxide, and prevents oxidative damage (7, 8), reduces inflammatory cytokines (TNF, IL-1b, IL-6, IL-8) induced by endotoxins (CO2 is potent against inflammation in sepsis) (9, 10, 11, 12). CO2 also protects against lipid peroxides and lowers prostaglandins. (13)
Lactate, on the other hand, has the opposite effect of CO2.
Lactate can cause vascular leakiness; including the blood-brain barrier (which leads to edema), can increase blood viscosity, impair circulation in the small vessels, can cause fibrosis (14), increase cortisol, increase prostaglandins and inflammation, increase angiogenesis (growth of new blood vessels), inhibit normal oxidative metabolism (Crabtree effect), increase the synthesis of new fatty acids, cause nerve cell loss, by increasing the release of excitotoxic glutamate, increase intracellular fat accumulation, and can cause ammonia (15). This reduction in pH, caused by lactate, is associated with mental conditions (16), increases intracellular calcium (calcification and excitation) (17), elevates adrenaline and noradrenaline, (18) and also fuels tumor and cancer growth, etc.
A good healthy cell will a pH level of around 6.8, and the pH outside the cell must be neutral, around the pH level of 7.4.
Normal oxidative metabolism creates about 13 times more ATP than through fermentation (lactate). The oxidation of fructose produces 8% more CO2 than glucose, and carbohydrates in general produce more CO2 than fats. Fats require ∼13% more oxygen than glucose to generate the same amount of ATP (19).
CO2 is made in the mitochondria of the cell, and lactate in the cytosol of the cell. The mitochondria appears to have a lactate transporter so that lactate can enter and be converted to pyruvate, via mitochondrial LHD (mLDH). (20) This is still just speculations by researchers, however, I think that if this is possible then why would pyruvate be converted to lactate in the cytosol, just to be reconverted to pyruvate in the mitochondria? I suggest that it’s most possibly because the person might have a thiamine and biotin deficiency. This then inhibits pyruvate entry into the mitochondria. Another reason could be because of a low NAD+/NADH ratio (because of a vitamin B3 deficiency), as the conversion of pyruvate to lactate uses NADH and converts it to NAD, thus improving the redox balance of the cell. This can all be corrected by improving thiamine, biotin and niacin status.
There are some studies showing that lactate is preferred as an energy source over pyruvate and fats, however, I disagree.
The reason the body reverts to lactate production, instead of oxidative metabolism, is because creating lactate is much easier than creating ATP via oxidative metabolism, which is much more complex. Making energy from lactate vs oxidative metabolism is like making energy from a coal factory vs a nuclear factory. The coal factory is much cheaper, but the energy production is much less compared to the nuclear factory.
Think about it. Glycolysis (the formation of pyruvate from carbs) is like a funnel. The bottom end goes into the mitochondria and is the rate limited step, which is controlled by thiamine (cofactor in the enzyme pyruvate dehydrogenase) and biotin (cofactor in the enzyme pyruvate carboxylase). The less thiamine and biotin you have, the more clogged up the funnel becomes, and this will make that the pyruvate builds up in the funnel and then runs over. This creates lactate. Lactate can then be used as energy where pyruvate could not, and then people think the body prefers lactate over glucose as an energy source, but it’s just because the funnel is blocked and the body is using an alternative route that is much less effective, yet easier to do. Instead, unblock the funnel and run optimally on oxidative metabolism, and not on lactate.
It’s also been shown that kids who are healthy recover faster than elite endurance athletes. This is because their body clears lactate very fast and they have a much higher pyruvate to lactate ratio than adults do. Whereas we as adults have lots of lactate floating around, hence we are more prone to anxiety and fatigue… and some people think it’s better than normal oxidative phosphorylation lol.
The Protocol that Smashes Serotonin and Endotoxin and causes Dopamine to Skyrocket!!
This dopaminergic diet is the best thing ever in a highly serotonergic Western environment.
So how do we increase CO2?…
Drop your anti-metabolic and catabolic stress hormones
Cortisol, adrenaline, serotonin and estrogen can all be seen as stress hormones, and by having them elevated leads to many problems in the body, and can eventually lead to all kinds of diseases.
These stress hormones inhibit normal oxidative metabolism, increase lactate and ammonia production, increase free fatty acid release, cause insulin resistance and less CO2 production.
Cortisol can be elevated due to quite a few reasons so check it out here on how to lower it…
Adrenaline could be elevated because of hypothyroid, stress, low blood sugar, insulin resistance, etc. Niacinamide, inosine, salt, sugar and GABA agonists, such as taurine, glycine, theanine, lemongrass, valerian root, magnesium, etc., will help lower adrenaline. If you have hypoglycemia between meals, consider snacking every 1-2 hours to keep blood sugar stable and prevent a rise in adrenaline. Also, consider meditation to help calm yourself and lower stress.
Lower estrogen by inhibiting the aromatase (article here), support the liver to detox estrogen (with milk thistle, lower cortisol, calcium-d-glutarate, garlic, etc.) and use estrogen receptor antagonists (vitamin A, D, K2, B6, niacinamide, caffeine, DHT, etc.)
Serotonin also potently inhibits normal cellular respiration. Read here on how to lower your serotonin.
Provide adequate nutrients to support oxidative metabolism
In order for your body to break carbs down into pyruvate, shuttle the pyruvate into the mitochondria and convert it into ATP, it requires quite a few nutrients.
In the electron transport chain (ETC), you have 4 complexes that accept electrons generated in the Kreb cycle. This enables the body to produce energy. Methylene blue, CoQ10, vitamin K2 and β-lapachone are electron acceptors similar to the complexes in the ETC, thus helping with energy production. If one of the complexes are defective, your energy production suffers. So by taking one of the three supplements mentioned below will aid in energy production.
- Oxidal – 400mcg methylene blue per drop, 240 drops (start with 12-13 drops daily)
- CoQ10 – 200mg per serving, 60 servings
- Vitamin K2 (MK4) – 1mg per drop, 1200 drops
- Lapodin – 5mg β-lapachone per serving, 30 servings (high topical absorption)
Iron, manganese (A) and magnesium (A) are also co-factors in various enzymes in the Kreb cycle and are very needed for energy production, with magnesium being the most important, as ATP must be bound to magnesium to be used.
- Magnesium glycinate – 200mg per cap, 180 caps
Thyroid hormones will boost mitochondrial function and speed up energy production. (21)
Lower free fatty acid release
Dietary polyunsaturated fatty acids (PUFAs) are directly anti-metabolic. PUFAs and their toxic breakdown products (prostaglandins, lipid peroxides, etc.) increases oxidative stress and inflammation, is anti-thyroid, interferes with glucose oxidation (Randle cycle and inhibits pyruvate dehyrogenase, pyruvate kinase, phosphofructokinase, cytochrome oxidase), increases cortisol, lowers protective steroid production, increases estrogen, etc.
Fructose, unlike glucose, has the advantage where the body can still utilize it even in the presence of elevated free fatty acids, such as with diabetes. However, consuming fructose and polyunsaturated fatty acids together will only lead to more problems, whereas fructose with saturated fats is a good combination for smooth energy production.
In the case of not being diabetic, consuming glucose will spike insulin, which will prevent the release of fatty acids from adipose tissue and increase glucose oxidation. However, as fatty acids are used by the mitochondria, and insulin is not inhibiting it (diabetes), the glucose will be converted to lactate, which will just further hamper proper oxidative metabolism.
Inhibit the enzyme carbonic anhydrase
Carbonic anhydrase is an enzyme which converts CO2 to bicarbonate. Inhibiting this enzyme will increase the amount of CO2 in the blood. Carbonic anhydrase inhibitors are anti-glaucoma, diuretic, anti-epileptic, and are also used to treat mountain sickness, intracranial hypertension, duodenal ulcers, neurological disorders, and even osteoporosis. (R)
Safe natural carbonic anhydrase inhibitors include thiamine (24), biotin, coffee, nicotine, pomegranate (1 oz of juice) (25), courmarin (found in cinnamon and citrus), capsaicin (chillies), ferulic acid (bamboo shoots and coffee), gallic acid (garlic), syringic acid (red wine and vinegar), salicylic acid (aspirin) (26), apigenin (dried parsley, guava), eriocitrin (lemons) (27) and testosterone (28).
Remove mitochondrial toxins
Mitochondrial toxins are substances which prevent the normal function of the mitochondria. These are toxins such as polyunsaturated fats, drugs, estrogenic (xenoestrogens, BPA, etc.) and anti-thyroid substances (goitrogenic vegetables, PUFAs), pesticides and herbicides, mold, heavy metals (lead, mercury, iron, etc.), metformin, etc.
It would be best to avoid these to ensure your mitochondria is able to function maximally.
Uncoupling is when the mitochondria is “wasting” electrons to produce heat through uncoupling proteins (UCP-1, 2 & 3), instead of making ATP. Electrons leave the mitochondria via the ETC, and then re-enters the mitochondria via UCPs instead of ATPase, producing heat, instead of ATP.
Uncoupling cells have a higher rate of oxygen consumption, they produce more CO2 and less free radicals, remove excess calcium from the cells (32), etc. The drug DNP is a potent uncoupler and is used as a fat loss aid. Overdosing, however, causes hyperthermia, fatigue, dizziness, restlessness, excessive sweating, etc.
Here are a few natural substances which increase uncoupling:
Nicotine (33), methylene blue (34), succinic acid (35), caffeine (36), aspirin (37), catecholamines (adrenaline and noradrenaline), vitamin E (38), progesterone, saturated fat (laurate, palmitate, myristate and stearate) (39, 40), vitamin A (41), vitamin D3 & calcium (42) (the active form of vitamin D, 1,25(OH)D suppresses UCP, but calcium increases UCP, and you need vitamin D to absorb calcium), fructose/glucose (pyruvate) (43), MCT oil (A) and thyroid hormones.
- Caffeine (200-400mg, three times daily)
- Methylene blue (15mg when used alone / 5mg (12-13 drops) when used as oxidal – once in the morning and once after lunch)
- Aspirin (1g on waking, 325mg every 2-3 hours thereafter)
- Calcium + vitamin D (1g + 1-2000IU depending on sun exposure, only once daily)
- Vitamin E (200IU, only once daily)
- Vitamin K2 (3-15mg)
- Thiamine (50mg three times daily)
- Niacinamide (100mg three times daily)
- Magnesium (200mg twice daily)
- MCT oil (1 tbsp)
Be sure to be well fed with carbs when taking this combo. Keep snacks at hand when you feel a slight hunger approaching, such as fruit (fresh, dried, juice), honey, etc. It is key to avoid polyunsaturated fatty acids (PUFAs) during this protocol as PUFAs are metabolic inhibitors. Taking gelatin with every protein-rich meal can also be helpful to balance the other amino acids, such as methionine and tryptophan, and it’s (glycine) an anti-inflammatory amino acid itself.
Lactate directly inhibits normal mitochondrial function, converts glucose into more lactate, in a feed forward loop, and reduces CO2 production. Lactate is also a NMDA agonist which can increase excitation.
Ammonia stimulates the formation of lactate, so lowering ammonia would be a good idea. Also, don’t consume too much protein in one meal as doing so is prone to convert to ammonia. Ammonia needs to be broken down into urea in the urea cycle, and requires arginine, citrulline, ornithine, manganese and CO2 in order to do so.
Lower endotoxins (inhibit TLR4)
Endotoxins are produced in the gut when food, which hasn’t been properly digested, ferments or rots in the gut. Gut bacteria feed on any undigested food particles and fibers and produce endotoxins. This endotoxin formation is even worse with insufficient stomach acid and digestive enzymes, as well as when being hypothyroid.
Endotoxins activate the TLR4 and its activation leads to the production of pro-inflammatory cytokines (TNF, IL-1β, IL-6, IL-18, etc.), immunosuppressive cytokines (IL-10, TGF-β, etc.) and angiogenic mediators (VEGF, EGF, TGF-β, etc.).
Endotoxins are also transported into the body, via chylomicrons, when fat is consumed with starches, and there the immune system also reacts negatively to it. Depending on your state of health, if you are more healthy, your body will not struggle much with the endotoxins, but when your body is already “sick”, it will react pretty badly to the endotoxins.
Endotoxins impair normal mitochondrial function, increase inflammation, nitric oxide, lactate, cortisol, prolactin and serotonin. They also inhibit the glucuronidation system, which prevents the liver from detoxifying toxins, such as estrogen and heavy metals, allowing them to accumulate.
Here are my recommendations on how to do so:
- Inhibit TLR4 with niacinamide, glycine, vitamin B2, vitamin A and vitamin D.
- Stay away from alcohol, morphine, serotonin and opioid agonists, as they increase TLR4 activation.
- 5-HT3 antagonists also inhibit TLR4. 5-HT3 antagonists include ginger, aspirin, progesterone, allopregnanolone, testosterone and ginseng. Also, just by lowering serotonin in general will lower 5-HT3 activation.
- Use natural anti-biotic fibers such as raw carrots, cooked bamboo shoots and/or boiled mushrooms.
- Use natural anti-microbial/anti-fungal agents such as oregano oil, grapefruit seed extract, cinnamon, garlic, coconut oil, MCT oil and vinegar.
- Remove toxins and bacteria from the gut with activated charcoal with coconut oil. Start with 1-2 tbsp of activated charcoal and 1-2 teaspoons of coconut oil before bed. Taking the charcoal with the coconut oil will prevent the absorption of the coconut oil in the small intestine, so that it can reach the large intestine and exert its anti-bacterial effect in the gut.
A few other useful tips:
- Avoid staying up too late at night, get a good amount of sleep in, and avoid darkness, as darkness is anti-respiratory.
- Bag breathing for 2-3 minutes can quickly increase CO2 and reduce lactate.
- Buteyko breathing can also help with relaxation, CO2 retention and improve breathing control.
- Sleep with a chin strap, or tape your mouth to keep your mouth closed and increase CO2 when sleeping, as sleeping with an open mouth will decrease CO2.
- Improve thyroid function, because one is more prone to hyperventilation during hypothyroidism.
- Inflammation is anti-respiration, so avoid things that might cause inflammation, and maybe use something anti-inflammatory.
- Ultraviolet, gamma, or x-rays, and even by blue light, is damaging to mitochondrial respiration. Red light helps restabilize your mitochondria and brings healing.
- Don’t take deep breaths, as this will result in a quick loss of CO2. Focus on breathing only through your nose, even when exercising.
- If you have a wound, continuously have it closed in something airtight for a few days (such as with a band-aid, bandage, or covered with honey). That area will then retain CO2 and reduce the possibility of leaving a scar.
- Not exactly a tip, but a cool fact none the less… Stormy weather, similar to high altitudes, allows the body to retain more carbon dioxide.
Hyperventilation can quickly lead to loss of CO2, thus a loss of tissue oxygenation, neural excitation, dizziness, chest pains and vascular palpations. And if this continues for prolonged periods of time, inflammation will increase and respiration will decrease, advanced glycation end-products (AGE) will form, a loss of minerals will occur and it will decrease the pH, due to a rise in lactate and ammonia.
Chronic elevated lactate is associated with hypothyroid, inflammation and nutrition deficiencies.