Energy Precursors Are an Emerging Area of Medicine
Written by GK Siska, PharmD
Adenosine triphosphate (ATP) is the magic and spark of life.
ATP is a biochemical firecracker that is needed before an embryo’s heart can start beating in its mother’s womb. ATP is given to the embryo by its mother. Without it, life cannot exist at any stage. ATP is needed for muscle movement, organ functions, and repairs to damaged tissues. It is no wonder that longevity researchers have zoned in on the biochemistry and manufacturing process of this chemical.
As we age, scientists can measure diminishing levels of ATP and other energy-related biochemicals in our bodies.1,2
In animal studies, particularly mice, researchers observe that the decline of these energy precursors goes hand in hand with age-related disease. They also observe that restoring these precursors has the potential to reverse certain diseases. They are doing work with the energy precursor NAD+, which is an active form of niacin found at the end stages of ATP production. The high-profile research, done by those such as Harvard professor David Sinclair, who discovered resveratrol, is being funded by young internet billionaires on a mission to reverse aging. They have discovered that NAD+ can play an integral role in reversing diseases, such as Alzheimer’s, atherosclerosis, depression, diabetes, and retinal degeneration.3,4
But nowhere is the role of ATP and health more apparent than in the heart. The heart muscle is the organ that uses the most energy. It has the highest oxygen uptake rate and has the highest concentration of mitochondria in the body.5
Some cardiologists are using energy building blocks to help patients with heart failure, and they are seeing positive results and increased quality of life.6,7
Ejection fraction (EF) is the scientific measurement used to measure the contraction and force of the heart muscle. EF is expressed as a percentage of how much blood the heart pumps out into the body with each contraction.
In his book, Metabolic Cardiology, cardiologist Stephen Sinatra, MD, outlines case studies of patients who had life-changing results from starting natural supplements to promote ATP synthesis.
With these products, he saw the EF increase from between 10% and 20% to between 40% and 50%. An EF fraction of 60% is normal, meaning that 60% of the total amount of blood in the left ventricle is pushed out with each heartbeat. An EF of between 10% and 20% means that the person has a mostly bedbound existence, with minimal movement.
Sinatra also includes case studies of people who stopped taking their energy precursor supplements, and their EF and quality of life went back to baseline, with an EF of 10% to 20%.
Energy precursor therapy (EPT) is being used in children with congenital mitochondrial disfunction. Children with these congenital defects often have profound cardiac disease, cognitive/brain dysfunctions, and/or muscle pain and weakness. These are the organ systems that use the most energy. Doctors at the Kennedy Krieger Institute in Baltimore, Maryland, use EPT to improve and mitigate the condition but not cure the disease.
Certain types of migraines also respond to EPT.8,9
Unlike the heart, the brain does not use mitochondria to make ATP. Instead, ATP is made in the surrounding fluid (the cytosol) through a less-efficient, quicker, simple method called hydrolysis. Therefore, the EPT for treating migraines is different from that of the heart.9
Could energy precursors play a role in other types of disease states, such as chronic fatigue syndrome and fibromyalgia? Functional medicine physicians are experimenting with it.10
What Do the Experts Say?
There is a Mitochondrial Medicine Society that follows these trends. These experts are an international group of clinicians, physicians, and researchers working toward advancing education, global collaboration, and research in clinical mitochondrial medicine. They discuss how healthy and young mitochondria yield good energy and health. Mitochondrial are factories or organelles that make ATP. Old mitochondria do not make ATP/energy efficient. To boost old mitochondria and create new mitochondria, it is necessary to exercise and build muscle. Interval training, a technique of exercising fast, such as sprinting for 1 minute and then more slowly, like fast walking for 3 minutes, and repeating this for 30 minutes, twice a week, is a good example of how to activate new mitochondria.11
They also discuss that providing the body with the building blocks for energy plays a vital role in creating new mitochondria and making adequate ATP. A healthy diet can also produce similar results. But when advanced age or disease are factors, dietary supplements can help (see Tables 1 and 2).
It is important to note that energy-producing dietary supplements and EPT are not stimulants and do not act in the same way that caffeine would. Stimulants, such as caffeine or methamphetamines, push out the stored energy into the bloodstream and tissues. Stimulants provide short-term energy and then leave the body depleted of ATP. Coincidently, methamphetamine users have a very high rate of heart failure compared with members of the public.12
Table 1. Building Blocks and Supplements for Energy6,7
|Energy Precursors||Role of Function in Energy Production||Additional Information|
|CoQ10, ubiquinol for better absorption
|Moves electrons around and is also an antioxidant; found in every cell of the body, with high concentrations in the kidneys, liver, and pancreas||Q is a substance that our bodies make. Levels in a 70-year-old are about 50% of those in a 20-year-old.|
|B vitamins||Have many roles and are building blocks for other energy biochemicals and antioxidants, such as Niacin, which is intimately involved in ATP synthesis||Commonly put in energy shots; NAD+ is an active form touted as a cure for aging. These vitamins have upper limits set by the FDA that should not be exceeded.|
|Creatine||Makes ATP and carries it to where it is needed||Found in high amounts in the brain and muscles; commonly used by bodybuilders|
|L-carnitine||A semi-synthetic amino acid found in red meat; lysine and other amino acids can be converted into L-carnitine, which carries fat particles into the ATP factory (mitochondria) and removes excess, potentially toxic acyl compounds and lactic acid.||Also used by fertility doctors to increase libido and sperm motility|
|Alpha-lipoic acid||A substance our bodies makes that has antioxidant properties with an affinity for fat molecules in membranes and nerves||Concerns exist about rare adverse thyroid effects in high doses.|
|Vitamin C||Moves electrons around to make ATP and also protects the membrane from damage as an antioxidant||Plays other longevity roles in the body, such as collagen formation in the skin and immune system support|
|Vitamin E||Thought to control oxidative damage to the mitochondrial membrane||Antioxidants are used to preserve the mitochondrial membranes that facilitate all the electron transfers. Rogue, flay away electrons damage the mitochondrial membrane.|
|Phosphate||Three of these molecules make up each ATP molecule.||Too much is dangerous and can cause deposits into soft tissues. A healthy body easily gets what we need from food. Supplementation is only needed in cases of alcoholism, malnutrition, and possibly other disease states. A simple blood test will tell if supplementation is needed.|
|Magnesium||Found in energy drinks; it is involved in many biochemical processes in our bodies.||Truly a powerful substance that makes every situation better through various mechanisms|
|D-ribose||The sugar that begins the metabolic process for the production of ATP||Effective for improving the heart’s tolerance to ischemia in patients with coronary artery disease.|
ADP indicatesAdenosine triphosphate.
Table 2. Traits of Energy Cocktails or Natural Supplement Regimens7,9,10,11
Use by functional medicine doctors for energy, general good health, and vitality in people 50 years and older or those with declining health: acetyl-l-carnitine (500 to 1,000 mg, twice a day); alpha-lipoic acid (100 to 200 mg, twice a day); B-complex vitamins (daily), Coenzyme Q10 (100 to 200 mg a day); D-ribose (5 g, once or twice a day); magnesium (150 to 300 mg, twice a day); and NADH (5 to 10 mg a day)
Use for congenital mitochondrial dysfunctions: highly variable and patient-specific, depending on the type of defect; tests are performed to determine the type of congenital defect, and then a product regimen is prescribed.11
Use for headaches: magnesium oxide (400 mg, twice a day) and riboflavin (200 mg, twice a day)
Use in heart failure: CoQ10 (90 to 150 mg a day); d-ribose (5 gm a day); magnesium 400 mg a day; and l-carnitine (500 to 1000 mg a day)
Drawbacks of Energy Precursors
All pills have the potential to cause harm. It is important to know what can go wrong with these products collectively and individually, to be on high alert for these occurrences, and if they do occur to take quick corrective action.
Sinatra speculated in his book that certain types of arrhythmias are caused and accelerated when ATP levels in the heart get too high or low. Energy levels should be in the natural zone and restored in balance with the other energy precursors.
Energy drinks and shots of high-dose B vitamins have been associated with fatal cardiac conditions.13
Also consider mitochondrial apoptosis and mitochondrial hormesis. Hormesis means the intervention or supplement is a double-edged sword. It has bad and good effects. The epic article hallmarks of aging discuss mitochondrial apoptosis and hormesis.1 Apoptosis is when the mitochondria will self-destruct when the cell becomes defective. Restoring energy precursors could potentially bypass this innate system. There is a concern that some of these products can lead to cancer if these energy precursors get too high or low.14
There is also the possibility that the prostate-specific antigen, which is a marker of prostate cancer, could rise after starting nicotinamide adenine dinucleotide therapy for longevity purposes.
Therefore, it is too early and experimental to recommend energy precursors for otherwise healthy people. Those who have symptoms of ATP deficits, such as heart failure, migraines, or heart failure, should only take these supplements under the watchful eye of a physician.
1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–1217. doi:10.1016/j.cell.2013.05.039
2. Aunan JR, Watson MM, Hagland HR, Søreide K. Molecular and biological hallmarks of ageing. Br J Surg. 103:e29-e46. doi:10.1002/bjs.10053
3. Johnson S, Imai SI. NAD + biosynthesis, aging, and disease. F1000Res. 2018;7:132. doi:10.12688/f1000research.12120.1
4. Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. 2018. doi:10.1038/s41467-018-03421-7
5. Long Q, Yang K, Yang Q. Regulation of mitochondrial ATP synthase in cardiac pathophysiology. Am J Cardiovasc Dis. 2015;5(1):19-32.
6. Houston M, Minich D, Sinatra ST, Kahn JK, Guarneri M. Recent science and clinical application of nutrition to coronary heart disease. J Am Coll Nutr. 2018;37(3):169-187. doi: 10.1080/07315724.2017.1381053
7. Sinatra ST. The Sinatra Solution; Metabolic Cardiology. 3rd ed. North Bergen, NJ: Basic Health Publications Inc; 2015.
8. Shaik MM, Gan SH. Vitamin supplementation as possible prophylactic treatment against migraine with aura and menstrual migraine. Biomed Res Int. 2015;2015:469529. doi:10.1155/2015/469529
10. Pizzorno J. Mitochondria-Fundamental to Life and Health. Integr Med (Encinitas). 2014;13(2):8-15.
11. Parikh S, Saneto R, Falk MJ, et al. A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol. 2009;11(6):414-430. doi: 10.1007/s11940-009-0046-0
12. Richards JR, Harms BN, Kelly A, Turnipseed SD. Methamphetamine use and heart failure: prevalence, risk factors, and predictors. Am J Emerg Med. 2018;36(8):1423-1428. doi: 10.1016/j.ajem.2018.01.001
13. Mangi MA, Rehman H, Rafique M, Illovsky M. Energy drinks and the risk of cardiovascular disease: a review of current literature. Cureus. 2017;9(6):e1322. doi:10.7759/cureus.1322
14. Poljsak B. NAD+ in cancer prevention and treatment: pros and cons. J Clin Exp Oncol. 2016;5:4. doi:10.4172/2324-9110.1000165