Why Diuretics Like Lasix Can Be Harmful for Children with Down Syndrome

---

​Children with Down syndrome face unique biochemical and metabolic challenges that demand special consideration when prescribing medications. One critical concern is the use of diuretics, such as furosemide (Lasix), which are commonly given to manage fluid overload in cases of congenital heart defects or pulmonary hypertension. While these drugs may be necessary in acute care, they are not without significant long-term risks, especially for children with Down syndrome.

Children with Down syndrome are already predisposed to thiamine (vitamin B1) deficiency due to a combination of factors, including:

• Malabsorption and gut dysbiosis
• Increased oxidative stress and mitochondrial dysfunction
• Higher metabolic needs for methylation and energy production

Thiamine is a critical cofactor for enzymes involved in mitochondrial energy production, including pyruvate dehydrogenase (PDH), alpha-ketoglutarate dehydrogenase, and transketolase. Without adequate thiamine, glucose metabolism is impaired, leading to lactic acidosis, fatigue, and neurodevelopmental delay.

Loop diuretics like furosemide cause urinary loss of thiamine, magnesium, potassium, and other electrolytes. This has been documented in both adult and pediatric populations. Studies show that furosemide therapy significantly reduces plasma and whole-blood thiamine levels, often to deficient levels, even after short-term use. (1, 2, 3, 4)

Children with Down syndrome are particularly vulnerable. When you add Lasix to an already thiamine-depleted child, you risk triggering a biochemical cascade that can manifest in serious and even life-threatening symptoms.

Thiamine deficiency in pediatrics can present subtly or with acute symptoms. These include:

• Fatigue, lethargy
• Poor feeding, vomiting
• Constipation, gastroparesis, and reflux
• Muscle weakness, hypotonia
• Developmental delays and irritability
• Tachypnea or labored breathing
• Cardiomegaly, heart failure symptoms

In its more advanced form, infantile beriberi (5), often under-recognized in modern pediatric medicine, can involve:

• Recurrent vomiting
• Aphonia (loss of voice)
• Edema and heart failure
• Lactic acidosis
  
• Esotropia (crossed eyes)
• Gastrointestinal dysmotility
• Sudden cardiovascular collapse

Several studies have linked thiamine deficiency with pulmonary hypertension, a common and life-threatening issue in children with Down syndrome, especially those with congenital heart defects or lung disease. (6, 7, 8)
​
Thiamine deficiency can lead to vasoconstriction and increased vascular resistance, possibly through disruption of mitochondrial energy metabolism in the pulmonary vasculature.

This means that giving Lasix to a child with Down syndrome and pulmonary hypertension, without concurrent thiamine repletion, can worsen the condition it was intended to treat.

Magnesium is another critical nutrient lost through diuretic therapy. It serves as a cofactor for hundreds of enzymes, including those involved in ATP production, nerve conduction, and muscle relaxation. Magnesium deficiency exacerbates thiamine deficiency, as these two nutrients work synergistically in the mitochondria.

For children with Down syndrome, any use of diuretics should be accompanied by proactive nutrient monitoring and supplementation of thiamine and magnesium. In many cases, high-dose thiamine in the form of benfotiamine or thiamine tetrahydrofurfuryl disulfide (TTFD) is well-tolerated and crosses cell membranes more effectively than standard thiamine HCl.

When supplementing a child on Lasix to prevent or correct thiamine and magnesium deficiency, age-appropriate dosing is key. Benfotiamine, a fat-soluble derivative of thiamine with superior cellular absorption, is generally well tolerated and effective. For children ages 1 to 3 years, a typical starting dose is 25-50 mg once daily. For ages 4 to 8, consider 50-100 mg daily, and for older children 9 and up, 100-150 mg per day is often appropriate. Some clinicians may use higher doses in acute deficiency or if symptoms of beriberi or pulmonary hypertension are present. 

Magnesium glycinate is commonly used to replenish magnesium lost through diuretics. A general guideline is 5-10 mg of elemental magnesium per kg of body weight per day, divided into 1-2 doses. For example, a 20 kg child might receive 100-200 mg of elemental magnesium daily. Always adjust dosing based on individual needs, lab markers, and clinical symptoms, and consult with a pediatric provider knowledgeable in nutritional medicine.

Recommended considerations:

• Supplement thiamine daily in children on Lasix or other diuretics
• Ensure adequate magnesium status via bloodwork (preferably RBC magnesium)
• Monitor for signs of fatigue, vomiting/reflux, constipation, or neurodevelopmental delay
• Re-evaluate the need for continued diuretic therapy as the child's condition stabilizes

Children with Down syndrome deserve care tailored to their unique metabolic needs. Diuretics like Lasix may offer short-term relief but come at the cost of worsening thiamine and magnesium deficiencies, nutrients essential for brain, heart, and mitochondrial function. By supplementing proactively and recognizing the symptoms of deficiency, we can prevent complications like pulmonary hypertension and support healthier development in these vulnerable children.

References:
1. Rieck J, Halkin H, Almog S, Seligman H, Lubetsky A, Olchovsky D, Ezra D. Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers. J Lab Clin Med. 1999 Sep;134(3):238-43. doi: 10.1016/s0022-2143(99)90203-2. 
2. Sica DA. Loop diuretic therapy, thiamine balance, and heart failure. Congest Heart Fail. 2007 Jul-Aug;13(4):244-7. doi: 10.1111/j.1527-5299.2007.06260.x.
3. Ritorto G, Ussia S, Mollace R, Serra M, Tavernese A, Palma E, Muscoli C, Mollace V, Macrì R. The Pivotal Role of Thiamine Supplementation in Counteracting Cardiometabolic Dysfunctions Associated with Thiamine Deficiency. Int J Mol Sci. 2025 Mar 27;26(7):3090. doi: 10.3390/ijms26073090.
4. Ryan MP. Diuretics and potassium/magnesium depletion. Directions for treatment. Am J Med. 1987 Mar 20;82(3A):38-47. doi: 10.1016/0002-9343(87)90131-8. 
5. Rabinowitz, SS. Pediatric Beriberi Clinical Presentation. Medscape, Mar 17, 2014​
6. Panigrahy N, Chirla DK, Shetty R, Shaikh FAR, Kumar PP, Madappa R, Lingan A, Lakshminrusimha S. Thiamine-Responsive Acute Pulmonary Hypertension of Early Infancy (TRAPHEI)-A Case Series and Clinical Review. Children (Basel). 2020 Oct 28;7(11):199. doi: 10.3390/children7110199.
7. Pache-Wannaz L, Voicu C, Boillat L, Sekarski N. Case Report: severe pulmonary hypertension in a child with micronutrient deficiency. Front Pediatr. 2025 Jan 31;13:1478889. doi: 10.3389/fped.2025.1478889.
8. C S, Kundana PK, Reddy N, Reddy B S, Poddutoor P, Rizwan A, Konanki R. Thiamine-responsive, life-threatening, pulmonary hypertensive crisis with encephalopathy in young infants: A case series. Eur J Paediatr Neurol. 2022 Jan;36:93-98. doi: 10.1016/j.ejpn.2021.12.010.