The Mitochondrial Cocktail: Essential Nutrition for Hormonal Health
Adrenal Hormones and Mitochondria
The synthesis of steroidal adrenal hormones starts in mitochondria, with cholesterol being converted to pregnenolone at the top of the hormonal synthesis cascade. From pregnenolone comes an entire family of downstream hormones including DHEA, testosterone, estrogen, progesterone, and cortisol. This comes about from the action of the cytochrome P450, a side-chain or cleavage enzyme, which exists on the mitochondrial inner membrane. Improper function of the mitochondria can lower adrenal hormone production, leading to Adrenal Fatigue Syndrome and other adrenal gland diseases. However, the mitochondrial cocktail of natural medicine can help prevent damage.
Thyroid Hormones and Mitochondria
Thyroid hormones are vital to the proper functioning of the mitochondria. These hormones affect mitochondria in two ways. First, thyroid hormone quickly stimulates cellular respiration. The second effect is an increase in the biogenesis of mitochondria and changes in the mitochondrial mass, which can occur from one to a few days after having hormone administration.
Thyroid hormones trigger the uncoupling of the process of oxidative phosphorylation using various mechanisms involving the proteins and lipids of the inner membrane of mitochondria. This enhanced uncoupling activity can increase the metabolic effects of taking thyroid hormones.
Additionally, 3,3’,5-triiodo-L-thyronine (T3) is actively involved in regulating mitochondrial function in a number of metabolically active tissues, which include the heart, liver, kidneys and skeletal muscles.
Mitochondrial Disorders and Adrenal Fatigue Syndrome
Adrenal Fatigue Syndrome (AFS) is a stress induced neuro-endocrine dysfunction of the body. The hallmark symptom is fatigue of unknown origin despite normal medical investigation. There are four clinical stages of clinical progression, from mild to severe. In advanced stages, one can be incapacitated and housebound, unable to work or lead a normal social life.
Most people with AFS carry on normal lives and are thus unaware of the potential negative natural progression of this condition until quite late. Allopathic physicians are ignorant of this condition and thus reject its notion. Do not be surprised if your doctor tells you AFS does not exist.
Many symptoms of mitochondrial disease and AFS are similar. Fatigue caused by a purposeful down regulation of bodily function to conserve energy in the case of AFS ultimately results in reduced formation of ATP from the mitochondria to achieve its effect. Diseases of mitochondrial dysfunction will result in a body that is unable to produce the necessary amount of ATP. The common clinical pathway for both AFS and mitochondrial disease is fatigue. In fact there are many similarities between common adrenal support supplements and the following “mitochondrial cocktail” supplement regimen detailed below.
Now there are no effective treatments for mitochondrial disease from a prescription medication perspective.
We know that many vitamins are required for synthesis of mitochondrial respiratory chain components. Biosynthesis of the key components of mitochondrial respiratory chain, coenzyme Q, for example, is dependent on vitamins B2, B6, B12, folic acid, pantethine, pantothenic acid, niacinamide and vitamin C.
As well, vitamins B1, B2, B6, niacin, biotin, folic acid, pantethine, and pantothenic acid are important for metabolic pathways in mitochondrial respiration and energy production. Vitamins C, E, niacin and folic acid are excellent scavengers of free radicals once formed. They help prevent mitochondrial oxidative damage and mitochondrial aging.
Many mitochondrial diseases are linked to vitamin deficiencies and can be improved by vitamin supplementation. Proper nutritional supplements targeted to enhance the mitochondria require a mitochondrial cocktail of sorts for best results.
Substrates to be considered for the mitochondrial cocktail include coenzyme Q10, L-carnitine, vitamin C, glutathione, B complex, trace minerals, marine phytoplanktons, pantethine and pantothenic acid, vitamin D, and magnesium.
Delivery System and Bioavailability
Because the mitochondrial is located inside the cell, fat-soluble nutrients such as vitamins A and E can reach it easily. They therefore tend to be more effective as mitochondrial anti-oxidants when compared to water-soluble nutrients like vitamins C and B, which are less able to cross the phospholipid bilayer cell wall comparatively speaking.
The advancement of nanotechnology and liposomal encapsulation technology offers a significantly enhanced oral liquid delivery system that overcomes this problem. Absorption is primarily in the small intestine rather than from the stomach. This dramatically improves assimilation and bioavailability. Always consider liposomal delivery systems for nutrients if available. Fortunately, this delivery system is available for glutathione, vitamin C, magnesium, vitamin D, and coenzyme Q10.
Phospholipids from lecithin remain the time tested and proven carrier of choice. Liposomal spheres so created are strong. Premature separation of the substrate from the carrier sphere is avoided. This is a common technical problem encounter when other forms are used. Care should be taken to avoid any formula that contains alcohol as a preservative. Always buy high quality brands because only advanced technology can prevent separation between the carrier lipid and the substrate, resulting in a liquid that is grainy instead of smooth if the liposomal is intact.
Liposomal Coenzyme Q10 (Ubiquinol)
Coenzyme Q10, also known as CoQ10, is an enzyme that is made by the body and is found in seafood. After about age twenty, and continuing as we age, the body’s production of CoQ10 slows down, declining by 50 percent. By age seventy, only 50 percent of the CoQ10 is produced by the body.
CoQ10 can be found in many different products including fatty fish (such as sardines) and organ meats such as heart, liver, and kidney. It can also be found in beef, soy, and peanuts. Diet alone does not provide sufficient CoQ10. For example, one pound of sardines or two-and-a-half pounds of peanuts are needed to provide 30 mg of CoQ10. Vitamin E, selenium, and the B vitamins all enhance and boost the biosynthesis of CoQ10 internally.
CoQ10 is a powerful antioxidant and stabilizes cell membranes. It also energizes and facilitates the efficiency of the mitochondria. The range of heart conditions for which research has found CoQ10 to be beneficial includes congestive heart failure, cardiomyopathy, arrhythmia, and angina when there is a lack of oxygen and muscular dystrophy. In some countries, cardiologists prescribe CoQ10 to patients with congestive heart failure routinely. In Japan, millions take CoQ10 as a prescription drug for cardiac problems.
The therapeutic effect of CoQ10 is highly dependent upon the delivery system.
Dosage Consideration: 100-300 mg per day in liposomal form for better bioavailabity. Much more is needed in case of cardiac failure.
L-carnitine is a semi-essential nutrient that acts as a transport carrier of fatty acid into the mitochondria where energy is produced. It is made from two essential amino acids (lysine and methionine). In addition to the transport function, L-carnitine helps in the metabolism of the fat within the mitochondria to generate energy. Studies have shown that dietary supplementation of L-carnitine markedly improves the overall mitochondrial function. The amount found in whole foods such as meat is unfortunately small.
Dosage Consideration: 300-2000 mg per day
Note: Taking L-carnitine with thyroid hormone might decrease the effectiveness of the thyroid hormone and make symptoms of hypothyroidism worse. Those with primary low thyroid function or secondary hypothyroidism from Adrenal Fatigue Syndrome should proceed with care. As well, L-carnitine might increase the effects of warfarin (Coumadin) and increase the chances of bruising and bleeding. Be sure to have your blood checked regularly. The dose of your warfarin (Coumadin) might need to be changed.
Arginine is also a semi-essential amino acid. It is a precursor to nitric oxide (NO) in the body. NO is an essential compound that helps blood circulation by relaxing blood vessels. It enhances blood flow so mitochondria in the heart muscle do not have to work as hard.
Even though the body normally makes enough, supplementation can be very beneficial when more protein is needed in the body. Those in advanced AFS where the body is in a catabolic state will find this nutrient very helpful in conjunction with a mitochondrial cocktail. In addition, people with protein malnutrition, excessive ammonia production and infections may not have enough arginine due to depletion.
Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver. Early studies have shown that arginine supplements may help treat erectile dysfunction (ED) in men with low nitrate levels in their blood or urine.
Dosage Recommendation: 500-6000 mg per day in powdered form. Higher doses of L-arginine can increase stomach acid and may aggravate symptoms in people with herpes. Those with low blood pressure need to be careful not to take too high a dose without supervision.
Reduced Liposomal Glutathione
Glutathione (GSH) is a key intracellular antioxidant and detoxifying enzyme. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including the mitochondria where its concentration in the matrix equals that of the cytosol. Almost 80 percent of people with chronic ailments are found to be deficient in glutathione. In fact, low levels of glutathione are involved in all disease states. For this reason glutathione supplementation is crucial in the mitochondrial cocktail. Glutathione promotes the healthy flow of electrons and maintains their steady supply in the body’s cells. This is the source of its effectiveness. Cells heal and live longer when electron flow is abundant and smooth. Poor flow of electrons corresponds to low energy, higher disease rates, low cell integrity, and cell death. Glutathione donates electrons to the body’s antioxidant pool, including antioxidants such as vitamin C, vitamin E, alpha-lipoic acid, and superoxide dismutase (SOD). In addition, glutathione neutralizes disease-causing oxidants and is capable of eliminating heavy metals. By protecting the body from free radicals and pathogenic attacks, it is keeping the cellular structure intact.
Dosage Recommendation: 50-400 mg per day of reduced glutathione in liposomal form for better bioavailability.
Some B vitamins are cofactors, which participate in important mitochondrial reactions. Only a small amount is needed. Most of the B vitamins have a bitter taste and are more palatable if flavored. B vitamins are water-soluble; that is, they are excreted if not used, and the benefit from taking these vitamins should be felt immediately. These factors make the B vitamins a safe yet effective part of the mitochondrial cocktail regimen. Thiamin is a cofactor for the pyruvate dehydrogenase complex, and in some patients has improved lactate and pyruvate levels. Thiamin has also helped some patients by improving their clinical symptoms.
Riboflavin (B2) is helpful for some patients with headaches and migraines, and is another important cofactor that participates in important mitochondrial reactions. Pantethine and pantothenic acid should also be considered for a mitochondrial cocktail.
Magnesium helps regulate neuromuscular activities of the cell and the mitochondria. The mitochondria cannot produce energy without this necessary component of the mitochondrial cocktail. Advanced age and a low plasma magnesium concentration are two key risk factors for poor mitochondrial function.
Unfortunately, the common American diet is high in calories and low in nutrition, resulting in a malnutrition epidemic of massive proportions. The modern day diet supplies limited magnesium per day, and most Americans are deficient in magnesium even by RDA standards of 300 mg a day and are not even aware of it. Common prophylactic intake of 400 mg to 1000 mg a day as a nutritional supplement is recommended. Excessive magnesium can cause diarrhea. Most can tolerate taking up to a 1000 mg supplement without problems. If you are getting loose stools, cut back and take just enough to avoid the runs. Do not take high levels of magnesium if you have kidney problems.
The best forms of magnesium for absorption are liposomalized magnesium gluconate and magnesium bisglycinate (magnesium bound to the amino acid glycine). With liposomal delivery, unabsorbed magnesium reaching bowl tolerance level and subsequent diarrhea and loose stools is avoided.
Dosage Recommendation: 100-500 mg as tolerated in liposomal form. Much more is needed for regular forms.
Liposomal Vitamin D
This hormone is normally produced in the skin using energy from sunlight. Vitamin D can also be found in a few foods—including fish, fish liver oils, egg yolks and fortified cereals but it can be effectively boosted with vitamin D supplements.
Vitamin D is vital for making our muscles work efficiently and boosting energy levels by enhancing mitochondria function. Muscle fatigue is a common symptom in vitamin D deficient patients, and this can be reversed with vitamin D supplementation.
Mitochondria use glucose and oxygen to make energy in a form that can be used to run the cell—an energy-rich molecule called ATP. Muscle cells need large amounts of ATP for movement and they use phosphocreatine as a ready and available energy source to make ATP. The mitochondria also replenish this phosphocreatine store after muscle contraction and measuring the time taken to replenish these stores is a measure of mitochondrial efficiency: better mitochondrial function is associated with shorter phosphocreatine recovery times. Low vitamin D levels were associated with reduced mitochondrial function, making vitamin D a key component of the mitochondrial cocktail.
Dosage Recommendation: 1000-10,000 IU. Much more may be needed for therapeutic effect or reversal of vitamin D deficiency. A liposomal delivery system is preferred. Oral sublingual intake in the morning is best for normal people. Nighttime administration is best for those with insomnia associated with AFS.
Liposomal Vitamin C
Despite the clinical importance of preventing mitochondrial oxidative damage, antioxidants such as vitamin C has limited effect primarily due to its limited ability to cross the cell wall from extracellular space to intracellular space where mitochondria is located.
Liposomal forms of vitamin C solves this problem as it is able to move through phospholipid bilayers and enables their accumulation on the mitochondrial matrix in response to the large, negative-inside mitochondrial membrane potential that does not require any specific import mechanism.
Within the mitochondria, ascorbic acid is released from the liposome. It goes to work and reduces mitochondrial oxidative stress.
Dosage Recommendation: 100-1200 mg per day in liquid liposomal form. The dosage range is very wide and depends on each person’s constitutional background, sensitivity, and history.
Mineral ascorbates (ascorbic acid combined with a mineral such as sodium) are water-soluble nutrients that have excellent extracellular anti-oxidative properties in quick release form and should also be considered in the mitochondrial cocktail. They are able to enter the mitochondria via facilitative glucose transporters and confer mitochondrial protection against oxidative injury as well, though at a much lower level. This allows them to reduce oxidative stress both within and outside the mitochondria.
Consider the combination of sodium ascorbate, calcium ascorbate, and magnesium ascorbate along with bioflavonoids and a small amount of ascorbic acid. They work well together. Not to be forgotten are important cofactors such as L-lysine, L-proline, malic acid, and citrus bioflavonoids. L-proline, L-lysine, and mineral ascorbates also support collagen synthesis. Malic acid helps to increase energy, and along with magnesium, helps to stabilize gastric intestinal irritation and relax tense muscles. Citrus bioflavonoids help make vitamin C more bioavailable to the cell.
Mineral ascorbates are best taken in conjunction with liposomal forms of vitamin C. Both forms work synergistically together for maximum sustained cellular delivery.
Dosage Recommendation: 500-2000 mg in powdered form.
© Copyright 2015 Michael Lam, M.D. All Rights Reserved.
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