FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, September 28, 2025

Why Early-Life Micronutrient Deficiency Leaves Lasting Damage - Even When Corrected Later

By Richard Z. Cheng, M.D., Ph.D. Editor-in-Chief

Editor's Note - OMNS receives many thoughtful reader questions, but our current platform doesn't support public Q&A. To foster more dialogue, I'll share selected letters and replies on my Substack (👉 https://substack.com/@rzchengmd ). OMNS will continue publishing articles from our editors and authors; this Substack Q&A is simply a complementary channel. I hope OMNS will add interactive features in the future so all editors can join the conversation. - Richard Z. Cheng, M.D., Ph.D., Editor-in-Chief

Introduction

Orthomolecular medicine emphasizes providing the body with the optimal concentrations of essential nutrients. Yet much of clinical nutrition focuses on correcting deficiencies only after they are discovered later in life. A crucial question is often overlooked: what happens if the deficiency occurred during early life-infancy, childhood, or even prenatally? Can later supplementation fully repair the damage?

While preparing for a cancer debate hosted by the Children's Health Defense, we identified ten categories of root drivers for cancer and other chronic diseases (Cheng, 2025, in preparation). One of these root drivers is Developmental & Early-Life Programming. This article takes a deeper look into that driver-focusing specifically on how micronutrient insufficiency during pregnancy, infancy, and childhood can leave permanent impacts that last a lifetime.

The emerging answer from animal and human studies is sobering: deficiencies in vitamins C and D during early life can cause changes in brain, immune, lung, and skeletal development that may never be fully reversed, even with later supplementation.

Vitamin C: Irreversible Impacts on Brain Development

Humans, like guinea pigs, cannot make their own vitamin C. Animal studies clearly show that when vitamin C is lacking during pregnancy or early childhood, the brain-especially the hippocampus, which controls learning and memory-suffers damage that cannot be fully repaired later.

Lasting hippocampal damage: Guinea pigs born to vitamin-C deficient mothers had smaller hippocampal volume and fewer new brain cells. Even after vitamin C was given later, the brain never fully caught up (1).

• Memory and neuron loss: In another study, young guinea pigs that lacked vitamin C early in life had fewer hippocampal neurons and poorer memory performance, confirming that early deficiency programs the brain for lasting problems (2).
• Synapse and neurotransmitter disruption: A follow-up study found that vitamin C deficiency also weakens the brain's communication system. The deficient animals had fewer connections between brain cells (fewer synapses) and disturbances in the balance of brain chemicals like serotonin. These changes help explain why the animals developed memory deficits that did not disappear, even after vitamin C was reintroduced (3).
• Vitamin C is not only an antioxidant but also a cofactor for enzymes regulating collagen synthesis and DNA demethylation (TET enzymes). These epigenetic roles suggest that deficiency during critical developmental windows can "program" long-lasting structural and functional changes (4).

Vitamin D: Programming Lungs, Immunity, and Bones for Life

Vitamin D is now recognized as a key hormone regulating development well beyond bones. A wealth of animal and human studies confirm that prenatal or early-life deficiency leaves long-term marks that supplementation later cannot fully erase.

• Lung Development: In mice, antenatal vitamin-D deficiency caused narrowed airways and simplified alveoli. Even after postnatal vitamin-D supplementation, tracheal narrowing persisted, and lung function remained impaired (5,6).
• Immune Programming: Prenatal vitamin-D deficiency left lasting "memory" in hematopoietic stem cells, skewing immune cell development long into adulthood (7,8).
• This cohort study showed that maternal vitamin D insufficiency was associated with lower whole-body and lumbar spine bone-mineral content in children at age 9, indicating persistent skeletal effects (9).
• This follow-up indicated that maternal vitamin D deficiency during pregnancy predicted lower peak bone mass in their children at age ~20, suggesting long-lasting skeletal programming (10).

Mechanistically, vitamin D deficiency during development influences epigenetic marks, gene expression, and hormone-sensitive signaling pathways, consistent with the Developmental Origins of Health and Disease (DOHaD) model (8,11-13).

While vitamins C and D are central examples, research shows that other essential micronutrients also have time-sensitive roles in shaping lifelong health. A brief overview illustrates just how broad this principle is.

Beyond C & D: Other Early-Life Micronutrients with Lasting Effects (and Excellent Safety When Used Appropriately)

Iodine - Brain Wiring Depends on It

Even mild iodine insufficiency in early pregnancy has been linked to lower verbal IQ and reading scores in school-age children. Timing matters: benefits are greatest when adequacy is ensured before or early in pregnancy (14-17).

Iron - Learning Circuits Need Iron on Time

Infancy is a high-risk window for iron deficiency. Follow-up studies into adolescence show persistent deficits in cognition, motor skills, and behavior after early-life iron deficiency, even when anemia is later corrected (18).

Folate (with B12) - Neural Tube Closure is a One-Time Event

Peri-conceptional folic acid prevents neural tube defects (NTDs); this is now standard of care worldwide because catch-up later is impossible. Low maternal B12 independently raises NTD risk and is associated with poorer early neurodevelopment; folate and B12 adequacy together are safest (19-23).

Choline - Attention and Information-Processing Speed

Randomized feeding trials show that maternal choline intake at ~2× current recommendations in the third trimester improved infant information-processing speed, consistent with choline's role in methylation and cell-membrane formation during brain development (24).

Omega-3 DHA - Vision and Early Cognition

DHA is a structural fat in the developing retina and brain. Randomized trials report better visual acuity and, in some studies, higher cognitive scores in infants receiving adequate DHA in milk/formula during early life (25-27).

Zinc - Growth, Immunity, and Neurodevelopmental Programming

Zinc participates in DNA/RNA synthesis and synaptic plasticity. Deficiency during gestation can alter neuronal development in animal models; in humans, maternal zinc supplementation reduces preterm birth in low-zinc settings (a risk factor for later problems). Neurodevelopmental benefits appear context-dependent; ensuring adequacy is prudent and safe (28-32).

Vitamin A (retinoids) - Lung Structure and Function

Retinoids guide airway and alveolar development. Maternal vitamin-A repletion at recommended levels improved offspring lung function years later in a randomized trial, underscoring a true developmental "window" (33-36).

Selenium - Thyroid and Redox Systems that Steer Development

Selenoproteins support thyroid-hormone activation and redox balance in the developing brain. Emerging human data link low maternal selenium to adverse pregnancy and child outcomes; adequacy is essential, though unlike C and D, selenium has a narrower margin of safety, meaning supplementation should stay within recommended ranges (37-41).

The Takeaway: Prevention, Not Catch-Up

These findings reinforce a central principle of orthomolecular medicine: timing matters. The body's critical growth periods demand optimal nutrition. Once developmental windows close, no amount of supplementation later may fully restore what was lost.

For clinicians, policymakers, and families, the implications are clear:

• Vitamin sufficiency must be ensured before conception, during pregnancy, and in early childhood.
• Routine screening of vitamin D and C status in pregnant women and young children should be a public health priority.
• Orthomolecular medicine provides a science-based framework for early, safe, and effective prevention.

Optimal nutrition during pregnancy and early childhood is one of the most cost-effective public health measures we have. Unlike pharmaceuticals, micronutrient sufficiency is safe, affordable, and universally accessible.

About the Author

Richard Z. Cheng, M.D., Ph.D. - Editor-in-Chief, Orthomolecular Medicine News Service

Dr. Cheng is a U.S.-based, NIH-trained, board-certified physician specializing in integrative cancer therapy, orthomolecular medicine, functional & anti-aging medicine. He maintains active practices in both the United States and China.

A Fellow of the American Academy of Anti-Aging Medicine and a Hall of Fame inductee of the International Society for Orthomolecular Medicine, Dr. Cheng is a leading advocate for nutrition-based, root-cause health strategies. He also serves as an expert reviewer for the South Carolina Board of Medical Examiners, and co-founded both the China Low Carb Medicine Alliance and the Society of International Metabolic Oncology.

Dr. Cheng offers online Integrative Orthomolecular Medicine consultation services.
📰 Follow his latest insights on Substack: https://substack.com/@rzchengmd

References

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