Mitochondria are known as the powerhouse of the cell. They are organelles that act like a digestive system which takes in nutrients, breaks them down, and creates energy rich molecules for the cell. This is known as cellular respiration.
Research indicates that poor mitochondrial energy production in people with Down Syndrome is an adaptive response to avoid injury and preserve basic cellular functions. This occurs due to a redox imbalance caused by the over expression of SOD1.
The reduced activity of mitochondria increases the likelihood that people with DS will also develop conditions related to poor energy metabolism such as Alzheimer’s Disease, diabetes and some forms of Autism Spectrum disorders. Poor mitochondrial activity alters the metabolism of Amyloid Precurser Protein and causes increases in oxidative stress.
Poor mitochondrial activity leads to brain fatigue as the brain requires a phenomenal amount of energy to function. When mitochondria are deficient we can’t adapt to stress, have a reduced capacity to fight viruses, can’t buffer calcium and prevent excessive glutamate (the excitatory neurotransmitter) in neurons. Poor mitochondrial activity is also associated with a sedentary lifestyle and increased rate of obesity in people with DS.
Pancreatic cells require a high metabolic rate to secrete digestive enzymes, and are compromised in DS. However pancreatic cells and insulin secretion improved following treatment with antioxidants and mitochondrial stimulation.
Which leads us to …
Pyrroloquinoline quinone (PQQ) stimulates the production of new mitochondria which is linked to many health benefits such increased longevity, improved energy utilization, and protection from reactive oxygen species. It has been researched and found to be beneficial in diseases associated with mitochondrial deficits such as DS.
CoEnzyme Q10 (vesisorb) has shown promising results for altered energy metabolism and oxidative stress in DS. It does this by reducing inflammation via suppression of NF-kB. Results in DS indicate effectiveness at improving DNA repair mechanisms.
L-Carnitine levels were lower in children with DS than typical children, is shown to enhance mitochondrial activity, balancing the effect of glutamate’s toxicity in the brain, and reducing stress levels. It improves nerve cell regeneration, protects nerve cells against toxins, increases Nerve Growth Factor and nerve cell activity.
Omega – 3 fatty acids and B vitamins were effective at reducing brain shrinking and increasing brain energy levels. They are crucial for energy production, being cofactors in the Krebs cycle and oxidative phosphorylation. A deficiency of vitamin B1 was associated with poor mitochondrial activity, reduced production of nerve cells, toxicity of nerve cells and inflammation in brain cells. Vitamin B12 status determines brain plasticity.
Vitamin C protects neurons. The brain has one of the highest concentrations of Vitamin C in the body, which it retains to protect cell walls and proteins from oxidative damage. Citrus bioflavonoids protect the brain and mitochondria by maintaining mitochondrial potential, reducing oxidative stress, decreasing membrane and DNA damage and increasing BDNF and brain plasticity.
Exercise, thyroid and phytochemicals
Exercise, thyroid hormones and a phytochemical rich diet increase the growth of new mitochondria and improve mitochondrial activity. Green Tea, Resveratrol and Turmeric are effective at supporting mitochondrial health by switching on PGC1a, the cellular master switch which increases hormesis – low dose stimulation with a beneficial effect . Infrared light also increases ATP production and reduces fatigue.
Mild dehydration of even a 1.5% reduction can reduce mitochondrial activity leading to fatigue and difficulty concentrating. High carbohydrate diets are associated with damage to mitochondria.
Magnesium maintains mitochondrial structure and function and blunts inflammation. It inhibits glutamate, reducing excitotoxicity, inhibits nitric oxide is antioxidant and anti – inflammatory and encourages brain regeneration.
Magnesium increases plasticity in the prefrontal cortex and a deficiency of magnesium increases stress hormone release, disrupts sleep patterns, affects memory and promotes inflammation in the brain. Magnesium was shown to be low in people with DS.
In conclusion, there are many ways we can increase mitochondrial activity and energy production in people with DS. This has so many benefits from better sleep to improved brain function and more energy for exercise. Following the guidelines above will ensure your child has energy for life and avoids the low energy pathologies which people with DS are susceptible to.
Arbuzova S, Hutchin T, Cuckle H. Mitochondrial dysfunction and Down’s syndrome. Bioessays. 2002 Aug;24(8):681-4.
Depeint F, Bruce WR, Shangari N, Mehta R, O’Brien PJ. Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact. 2006 Oct 27;163(1-2):94-112. Epub 2006 May 1.
Hamidie RD, Yamada T, Ishizawa R, Saito Y, Masuda K. Curcumin treatment enhances the effect of exercise on mitochondrial biogenesis in skeletal muscle by increasing cAMP levels. Metabolism. 2015 Oct;64(10):1334-47.
Helguera P, Seiglie J, Rodriguez J, Hanna M, Helguera G, and Busciglio J.Adaptive Downregulation of Mitochondrial Function in Down Syndrome.Cell Metab. 2013 Jan 8; 17(1): 132–140.
KC S, Cárcamo JM, Golde DW. Vitamin C enters mitochondria via facilitative glucose transporter 1 (Glut1) and confers mitochondrial protection against oxidative injury. FASEB J. 2005 Oct;19(12):1657-67.
Kubotaa T, Shindoa Y, Tokunoa K, Komatsub H, Ogawac H, Kudod S, Kitamuraa Y, Suzukib K, e, Okaa K. Mitochondria are intracellular magnesium stores: investigation by simultaneous fluorescent imagings in PC12 cells. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research. Volume 1744, Issue 1, 15 May 2005, Pages 19–28
Marie Lagouge, Carmen Argmann, Zachary Gerhart-Hines, Hamid Meziane, Carles Lerin, Frederic Daussin, Nadia Messadeq, Jill Milne, Philip Lambert, Peter Elliott, Bernard Geny, Markku Laakso.
Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α. Cell Volume 127, Issue 6, 15 December 2006, Pages 1109–1122
Miles MV, Patterson BJ, Schapiro MB, Hickey FJ, Chalfonte-Evans M, Horn PS, Hotze SL. Coenzyme Q10 absorption and tolerance in children with Down syndrome: a dose-ranging trial.Pediatr Neurol. 2006 Jul;35(1):30-7.
Monteiro CP, Varela A, Pinto M, Neves J, Felisberto GM, Vaz C, Bicho MP, Laires MJ.Effect of an aerobic training on magnesium, trace elements and antioxidant systems in a Down syndrome population. Magnes Res. 1997 Mar;10(1):65-71.
de Oliveira MR, Jardim FR, Setzer WN, Nabavi SM, Nabavi SF. Curcumin, mitochondrial biogenesis, and mitophagy: Exploring recent data and indicating future needs. Biotechnol Adv. 2016 Sep-Oct;34(5):813-26.
Pagano G, Castello G. Oxidative stress and mitochondrial dysfunction in Down syndrome. Adv Exp Med Biol. 2012;724:291-9.
Rehman H, Krishnasamy,Y, Haque,K, Thurman, RG, Lemasters, JJ ,Schnellmann,RG and Zhong Z. Green Tea Polyphenols Stimulate Mitochondrial Biogenesis and Improve Renal Function after Chronic Cyclosporin A Treatment in Rats. PLoS One. 2013; 8(6): e65029. Published online 2013 Jun 3
Seven M, Cengiz M, Tüzgen S, Iscan MY. Plasma carnitine levels in children with Down syndrome. Am J Hum Biol. 2001 Nov-Dec;13(6):721-5.
Schroeder EK, Kelsey NA, Doyle J, Breed E, Bouchard RJ, Loucks FA, Harbison RA, Linseman DA. Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal. 2009 Mar;11(3):469-80.
Tiano L, Busciglio J. Mitochondrial dysfunction and Down’s syndrome: is there a role for coenzyme Q(10). Biofactors. 2011 Sep-Oct;37(5):386-92.
Tiano L, Padella L, Santoro L, Carnevali P, Principi F, Brugè F, Gabrielli O, Littarru GP.Prolonged coenzyme Q10 treatment in Down syndrome patients: effect on DNA oxidation. Neurobiol Aging. 2012 Mar;33(3):626.e1-8.
Tiano L, Padella L, Carnevali P, Gabrielli O, Bruge F, Principi F, Littarru GP. Coenzyme Q10 and oxidative imbalance in Down syndrome: biochemical and clinical aspects. Biofactors. 2008;32(1-4):161-7.
Ungvari,Z, Sonntag, WE, de Cabo, R, Baur,J A and Csiszar A.Mitochondrial Protection by Resveratrol. Exerc Sport Sci Rev. 2011 Jul; 39(3): 128–132.