Guest blogger Erica Peirson ND writes about ways to optimize the health of a child or adult with Down syndrome.
Ever since the extra chromosome was discovered in 1959, physicians and researchers have been searching for answers on how to best support the health of those with Down syndrome. Some have even been searching for ways to lessen the phenotype or physical characteristics altogether.
While it isn’t my goal to change the characteristics of Down syndrome or their physical appearance, I have found that their health can be optimized by addressing the root cause of their health issues, which isn’t always just genetic. While they do experience health and biochemical tendencies, they are all unique and benefit from an individualized approach just as anyone else does. The health tendencies to watch closely for are:
- Gastrointestinal issues
- Mitochondrial dysfunction
- Methylation issues
- Nutrient deficiencies
- Immune dysfunction
- Nervous system dysfunction
- Sleep issues
- Glucose metabolism issues
Many of these issues are connected as an issue in one area can cause issues in another. I won’t be able to fully review all of the intricacies of each of these areas in the scope of this article, but I will summarize key areas within gut health, nutrient deficiencies, glucose metabolism and nervous system function.
I would be remiss if I didn’t review the importance of recognizing the biochemical individuality of those with Down syndrome. This concept is reviewed in the paper “The importance of understanding individual differences in Down syndrome”, written in 2016 by a team of clinicians and researchers headed by Dr. Annette Karmiloff-Smith. In this paper they state, “With full trisomy, intuitively it might be assumed that expression levels of triplicated genes are 1.5-fold that of the euploid population. However, this is not so.”
Anyone who studies genetics knows that genetic expression is extremely complicated and controlled by many biochemical and environmental epigenetic factors. The extra chromosome in those with Down syndrome does not simply sit passively within cells generating proteins and enzymes at the same rate in each person.
The authors conclude in this paper, “Many other genetic, epigenetic, and environmental factors play a role in how the Down syndrome phenotype expresses itself in each individual.” I couldn’t agree more. All of the factors that make any of us unique also apply to those with Down syndrome and include:
- Gut health
- Sleep habits
- Medications (antibiotics)
- Toxin exposure
- Mindset of those around us
- Our own mindset
- All of our genes
Each of these things could be expanded that would make this list incredibly long. Dismissing health issues in those with Down syndrome as being caused only by the presence of their extra chromosome while ignoring the multiple ways that their health can be optimized is doing them a great disservice. The term for this is “diagnostic overshadowing”, and it results in an increase rate of morbidity and mortality in those with Down syndrome.
It’s been well-established that children with Down syndrome have a tendency for low muscle tone. Let’s not forget that the gut is a very muscular organ system. Low muscle tone, therefore, leads to slow gut motility. This is the case for any child or adult.
Low muscle tone and slow gut motility increase the risk of small intestinal bacterial overgrowth (SIBO) and/or yeast overgrowth. This overgrowth of bacteria and yeast leads to malabsorption which results in nutrient deficiencies and further low muscle tone and even nervous system damage that can further impair gut motility.
It’s a vicious cycle (see above image) that can wreak havoc on the health and development of any child, regardless of their genetics.
Acetylcholine Important for Health
The health of the nervous system dysfunction is closely tied to glucose metabolism because acetylcholine (Ach) is one of the most abundant neurotransmitters in the human body, found in both the peripheral and central nervous system. It’s essential for:
- Skeletal function
- Smooth muscle function
- Gut motility
- Blood-vessel dilation
- Heart rate regulation
- Many other functions of the body
Symptoms of low acetylcholine include:
Acetylcholine production in the body is dependent on the presence of adequate amounts of building blocks to make it. Those building blocks are acetyl CoA and choline. Here’s where glucose metabolism comes in. Acetyl CoA is made from a byproduct of glycolysis, the process by which glucose is broken down into two molecules of pyruvate.
Pyruvate is then converted to acetyl CoA via an enzyme called pyruvate dehydrogenase. This enzyme is essentially the front door of mitochondria. It’s a key step to not only making acetyl CoA but also to all of mitochondria function. If this enzyme doesn’t work properly then we get low acetyl CoA, low acetylcholine and poor mitochondrial function. It’s that important.
This enzyme will not function without its helpers or cofactors. Those are vitamin B1, vitamin B2 and alpha lipoic acid. We’ve detected significant deficiencies in vitamin B1 and vitamin B2 in many of our patients with Down syndrome. We pick up on these deficiencies by not dismissing the signs as simply just due to the child having Down syndrome.
We also detect them through organic acid testing, which detects elevations in metabolites that denote a deficiency in these vitamins. The table below lists just some of the symptoms of a deficiency in these vitamins that are key to the production of acetylcholine and mitochondrial function, among many other biochemical processes within the body.
Common Vitamin Deficiencies
Signs and symptoms of vitamin B1 deficiency:
- Esotropia, strabismus (crossed eyes or “lazy”eye)
- Ptosis (drooping eyelid/s)
- Peripheral neuropathy (paresthesia and hyperesthesia usually begin with the lower extremities and gradually involve the upper extremities and perioral area)
- Delayed gross motor skills
- Difficulty breathing (pulmonary hypertension)
- Edema (swollen abdomen, face or extremities)
- Hyporeflexia (diminished or absent deep tendon reflexes)
- Foot and wrist drop (heavy step and limp wrist)
- For a comprehensive list please refer to Pediatric Beriberi Clinical Presentation
Signs and symptoms of vitamin B2 deficiency:
- Glossitis (inflammation, swelling, redness of the tongue)
- Pontobulbar palsy (feeding and speech issues)
- Sensory gait ataxia (clumsy, staggering walk)
- Hearing loss (auditory neuropathy)
- Respiratory compromise (diaphragm weakness/sleep apnea)
- Angular stomatitis (lesions at the corners of the mouth)
- Cheilosis (swollen, cracked lips)
- Hair loss
- Seborrheic dermatitis (moist, scaly skin inflammation)
SIBO a Significant Cause of Malabsorption
Many of the above symptoms are commonly experienced by those with Down syndrome and can potentially be remedied by supplementing with vitamins B1 and B2. The root cause of these deficiencies is often malabsorption and must also be addressed. A significant cause of malabsorption is SIBO, which is common in children with Down syndrome and made worse by the resulting vitamin deficiencies (recall the vicious cycle).
Dr. John K. DiBaise thoroughly explains the mechanism of malabsorption that occurs in SIBO in his paper Nutritional Consequences of Small Intestinal Bacterial Overgrowth. He discusses deficiencies in vitamins B12, A, D and E, iron, thiamine (B1) and nicotinamide (B3) as experienced by those with SIBO.
Treating SIBO is an actionable step that can greatly improve intestinal absorption and overall gut health. SIBO can be treated with antimicrobial herbal formulas like Biocidin, gut motility agents like ginger, carnitine and aloe and the temporary use of the low-FODMAP diet.
Treating SIBO along with providing the vitamins found to be deficient can ultimately lead to improved nutrient absorption and amelioration of the symptoms of these micronutrient deficiencies that are often seen in those with Down syndrome. The nutrients found to be deficient will be unique for every child due to the great amount of variation seen in the degree of SIBO, differences in diet and other factors that impact gut health.
Nutritional Deficiencies and Biochemical Imbalances
I’ve highlighted just two vitamin deficiencies here that we often detect in our patients with Down syndrome. These two vitamins are extremely important for glucose metabolism, acetylcholine synthesis and mitochondrial function, which have all been shown to be impaired in individuals with Down syndrome. (1, 2, 3, 4)
We screen for many other vitamin deficiencies and biochemical imbalances by taking a thorough medical history, reviewing all signs and symptoms of potential deficiencies and running blood, urine and stool tests when possible.
Micro- and macronutrient deficiencies in children with Down syndrome should not be ignored and the symptoms not dismissed as “normal for Down syndrome”. This article only touches briefly on the number of ways children and adults with Down syndrome can be supported through nutrition, diet, supplements and supporting gut health.
Other Ways to Support Health
Many parents are using other means to support their child’s health and development like neurodevelopmental programs, reflex integration, regular exercise, oral motor exercises, qi gong massage, palate expansion and other therapies that are considered “alternative”.
Simply raising their expectations for their child beyond what history and experts lead them to believe their child is capable of can do a lot for a child with Down syndrome. Homeschooling is often chosen by parents of children with Down syndrome when possible as well. Education experts not understanding the unique learning style and their biased, low expectations can be a significant disadvantage to a child with Down syndrome.
Parents today are looking outside the box, understanding that if we continue to do what has historically been done for children and adults with Down syndrome we will continue to get the same results. Medical and educational professionals and society as a whole all have to do better for these children and adults with Down syndrome who deserve a seat at the table because they have so much to offer when given the opportunity to thrive.
The Basics of Optimizing the Health of Children with Down Syndrome
- Recognize that every infant, child and adult with Down syndrome is unique.
- Don’t ever let any doctor dismiss your health concerns for your child as just part of Down syndrome. This is common and results in health issues going unaddressed. Learn to advocate and push boundaries with professionals. Ask questions like:
- “How would you treat this in a child without Down syndrome?”
- “Are there additional tests you would run or something else you might rule out?”
- Optimize gut health:
- Optimize gut motility
- Avoid antibiotics whenever possible
- Gluten-free, dairy-free diet
- Encourage whole, gluten-free grains (oats) and vegetables
- Low histamine
- Bloating is a symptom of small intestinal bacterial overgrowth and or yeast overgrowth in the gut. These are common and secondary to slow gut motility, antibiotics and/or acid blocking medication
- Probiota HistaminX
- Optimize gut motility
- Vitamin deficiencies are common in children with Down syndrome often secondary to gut malabsorption. Many of these deficiencies, especially of the B vitamins can impair nervous system function causing delayed gross motor skills, delayed fine motor skills, swallowing issues and more. Learn to recognize these symptoms.
- Raise expectations
- Labs to keep an eye on with optimal reference ranges:
- Free T4
- Free T3
- Reverse T3
- Vitamin D
- Serum B12
- Magnesium, RBC
- Histamine, whole blood
- Glutathione, total
- Serum zinc
- Serum copper
- Pietrini, P., et al. Low glucose metabolism during brain stimulation in older Down’s syndrome subjects at risk for Alzheimer’s disease prior to dementia. Am J Psychiatry. 1997 Aug;154(8):1063-9.
- Labudova, O., et al. Impaired brain glucose metabolism in patients with Down syndrome. J Neural Transm Suppl. 1999;57:247-56.
- Fodale,V., et al. The cholinergic system in Down’s syndrome. J Intellect Disabil. 2006 Sep;10(3):261-74.
- Izzo, A., et al. Mitochondrial dysfunction in down syndrome: molecular mechanisms and therapeutic targets. Mol Med. 2018;24(1):2. Published 2018 Mar 15.
About Erica Peirson ND
In 2007, Dr. Peirson gave birth to her son, Miles, who was diagnosed with Mosaic Down Syndrome. Ever since then, she has been on a quest to learn everything there is to know about Down syndrome, including treatments.
Her frustration with the little amount of information she received from the specialists they saw fueled her desire to learn more.
Dr. Peirson wants to share what she has learned and give others the tools they need to help their child be the best they can be.
Dr. Peirson graduated from the National University of Naturopathic Medicine in 2005 and is a licensed primary care physician under Oregon State Law. Before completing her undergraduate degree in Biology from Portland State University, she worked as an EMT in an Emergency Room in Clearwater, FL and thus has a great understanding of and appreciation for conventional medicine.
Until recently Dr. Peirson taught Cell Biology and Anatomy & Physiology at Portland Community College, where she gained great satisfaction from teaching students about the amazing processes of the body.
You can find out more about Dr. Peirson’s work at her website: https://www.peirsoncenter.com/
Sources & References
Al-Gazali, L.I., et al. Abnormal folate metabolism and genetic polymorphism of the folate pathway in a child with Down syndrome and neural tube defect. Am J Med Genet. 2001 Oct 1;103(2):128-32.
Amorim, M.R., et al. MTHFR 677C–>T and 1298A–>C polymorphisms in children with Down syndrome and acute myeloid leukemia in Brazil. Pediatr Hematol Oncol. 2008 Dec;25(8):744-50.
Bianchi, P., et al. Lithium restores neurogenesis in the subventricular zone of the Ts65Dn mouse, a model for Down syndrome. Brain Pathol. 2010 Jan;20(1):106-18.
Brandalize, A.P.C., et al. Evaluation of C677T and A1298C polymorphisms of the MTHFR gene as maternal risk factors for Down syndrome and congenital heart defects. Am J Med Genet. 2009 Oct;149A(10):2080-7.
Cantor, D.S., et al. A report on phosphatidylcholine therapy in a Down syndrome child. Psychological Reports. 1986, 58, 207-217.
Chung, S.Y., et al. Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia. J Nutr. 1995 Jun;125(6):1484-9.
Lithium rescues synaptic plasticity and memory in Down syndrome mice. J Clin Invest. 2013 Jan;123(1):348-61.
Cyril, C., et al. MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case-control study from South India. Indian J Hum Genet. 2009 May;15(2):60-4.
De la Torre, R., et al. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol Nutr Food Res. 2014 Feb;58(2):278-88.
DiBaise, J.K. Nutritional consequences of small intestinal bacterial overgrowth. Practical Gastroenterology. 2008. 32(12), 15-28.
Dutta, S., et al. Risk of Down syndrome conferred by MTHFR C677T polymorphism: Ethnic variations. Indian J Hum Genet. 2007 May-Aug; 13(2): 76–77.
Fodale, V., et al. The cholinergic system in Down’s syndrome. J Intellect Disabil. 2006 Sep;10(3):261-74.
Hobbs, C.A., et al. Polymorphisms in Genes Involved in Folate Metabolism as Maternal Risk Factors for Down Syndrome. Am J Med Genet. 2000 Sep; 67(3): 623–630.
Hung, M.C., et al. Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine-vitamin B12 diet. Br J Nutr. 2001 Aug;86(2):163-71.
Izzo, A., et al. Mitochondrial dysfunction in down syndrome: molecular mechanisms and therapeutic targets. Mol Med. 2018;24(1):2. Published 2018 Mar 15.
Jovanovic, S.V., et al. Biomarkers of oxidative stress are significantly elevated in Down syndrome. Free Medic Biol Med. 1998 Dec;25(9):1044-8.
Karmiloff-Smith, A., et al. The importance of understanding individual differences in Down syndrome. F1000Res. 2016 Mar 23;5:F1000 Faculty Rev-389.
Kokotas, H., et al. Investigating the impact of the Down syndrome related common MTHFR 677C>T polymorphism in the Danish population. Dis Markers. 2009;27(6):279-85.
Labudova, O., et al. Impaired brain glucose metabolism in patients with Down syndrome. J Neural Transm Suppl. 1999;57:247-56.
Lima, A.S., et al. Nutritional status of zinc in children with Down syndrome. Biol Trace Elem Res. 2010 Jan;133(1):20-8.
Liu, F., et al. Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome. FASEB J. 2008 Sep; 22(9): 3224–3233.
Lockrow, J., et al. Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model. Exp Neurol. 2009 Apr;216(2):278-89.
Maternal polymorphisms 677C-T and 1298A-C of MTHFR, and 66A-G MTRR genes: is there any relationship between polymorphisms of the folate pathway, maternal homocysteine levels, and the risk for having a child with Down syndrome? Am J Med Genet. 2006 May 1;140(9):987-97.
Meguid, N.A., et al. MTHFR genetic polymorphism as a risk factor in Egyptian mothers with Down syndrome children. Dis Markers. 2008;24(1):19-26.
Moon, J., et al. Perinatal choline supplementation improves cognitive functioning and emotion regulation in the Ts65Dn mouse model of Down syndrome. Behav Neurosci. 2010 Jun;124(3):346-61.
Nachvak, S.M. α-Tocopherol supplementation reduces biomarkers of oxidative stress in children with Down syndrome: a randomized controlled trial. Eur J Clin Nutr. 2014 Oct;68(10):1119-23.
Napolitano, G., et al. Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome? Ann Genet. 1990;33(1):9-15.
Oka, A., et al. The up-regulation of metabotropic glutamate receptor 5 (mGluR5) in Down’s syndrome brains. Acta Neuropathol. 1999 Mar;97(3):275-8.
O’Leary, V.B., et al. MTRR and MTHFR polymorphism: link to Down syndrome? Am J Med Genet. 2002 Jan 15;107(2):151-5.
Parisotto, E.B., et al. Antioxidant intervention attenuates oxidative stress in children and teenagers with Down syndrome. Res Dev Disabil. 2014 Jun;35(6):1228-36.
Pietrini, P., et al. Low glucose metabolism during brain stimulation in older Down’s syndrome subjects at risk for
Alzheimer’s disease prior to dementia. Am J Psychiatry. 1997 Aug;154(8):1063-9.
Reutter, H., et al. MTHFR 677 TT genotype in a mother and her child with Down syndrome, atrioventricular canal and exstrophy of the bladder: implications of a mutual genetic risk factor? Eur J Pediatr. 2006 Aug;165(8):566-8.
Starbuck, J.M., et al. Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome. Sci Rep. 2021 Feb 25;11(1):4715.
Stringer, M., et al. Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes. Physiol Behav. 2017 Aug 1;177:230-241.
Takeda, A., et al. Release of glutamate and GABA in the hippocampus under zinc deficiency. J Neurosci Res. 2003 May 15;72(4):537-42.
Tanzi, R.E., et al. Neuropathology in the Down’s syndrome brain. Nature Medicine. 1996; (2)31–32.
Vacca, R.S., et al. Green tea EGCG plus fish oil omega-3 dietary supplements rescue mitochondrial dysfunctions and are safe in a Down’s syndrome child. Clinical Nutrition. 2015 1-2.
Valenti, D., et al. Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down’s syndrome. Biochim Biophys Acta. 2013 Apr;1832(4):542-52.
Wang, S.S., et al. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China*. J Zhejiang Univ Sci B. 2008 Feb; 9(2): 93–99.