Higher Antibody Levels After Vaccinations
The infants produced more antibodies with nucleotides than with conventional formula or breast milk.
Studies on Nucleotides
Nucleotides and the Immune System: What Does the Research Say?
- When your body fights off pathogens, immune cells multiply rapidly. Each new cell requires nucleotides—the building blocks of DNA and RNA. We explain exactly what they are on our Nucleotides page. Here, we summarize what research has found about nucleotides and the immune system—and where the limits lie. The Most Important Points at a Glance
- Nucleotides from food are considered conditionally essential: When immune cells need to multiply rapidly, the body's own production may not be sufficient.
- The strongest evidence comes from infants: A meta-analysis of 15 studies found that nucleotide-enriched formula led to better immune responses to vaccination.
- In adult athletes, small studies showed more stable immune parameters after intense exercise.
- Animal studies show how nucleotides might affect the immune system.
- Whether nucleotides protect against infections in everyday life has not been studied.
STRONGEST EVIDENCE
Meta-analysis of 15 studies involving infants
Researchers have synthesized data from 15 studies in which infants were given formula with or without nucleotides. This allows them to piece together an overall picture from many individual findings.
fewermore antibodies →
15 individual studies, one overall result
Schematic representation; not the original data
15
Studies Analyzed
Infants
study group
3 vaccinations
Hib, Diphtheria, Polio
Meta-analysis
highest level of study
Less Diarrhea
The authors cite reduced incidence of diarrhea as another benefit, with greater effects observed at higher intake levels.
HOW TO READ THE PROGRAM OVERVIEW
Not every study carries the same weight. That is why we specify the type of study and the group under investigation for each study.
-
Meta-analysis
Analyzes the data from multiple studies collectively. Is considered particularly meaningful.
very high -
Randomized study
Participants are randomly assigned to groups. This is the most reliable way to test for effects.
high -
Review
A review article that summarizes the current state of knowledge.
medium -
Pilot Study
A small preliminary study that provides initial indications but does not yet allow for definitive conclusions.
medium -
Animal study
Studies animals in the laboratory. Reveals possible mechanisms, but the findings cannot be directly applied to humans.
initial indications
Now you're ready: Discover what research has found out about nucleotides and the immune system, and form your own opinion. You can read all the original sources with just one click.
1
GROUP 1 · STRONGEST EVIDENCE
Review Articles and Meta-Analyses
What research has found overall about nucleotides and the immune system.
5Work
1Meta-analysis
4Reviews
This group
Meta-Analyses & ReviewsRandomized Trials, Studies, and Sources on the Immune SystemStudies in HumansAnimal Studies
The higher the level, the greater thesignificance. Click on a level to jump to the studies.
Nucleotides from Food and Immune Function
Kulkarni AD, Rudolph FB, Van Buren CT (1994). The role of dietary sources of nucleotides in immune function: a review. Journal of Nutrition 124(8 Suppl):1442S–1446S.PubMed ↗
Review
Nucleotides from food appear to be important for the cellular immune response, especially when the immune system is under significant stress.
Effects on Immune Cells, the Intestines, and the Liver
Carver JD (1994). Dietary nucleotides: effects on the cellular immune system, the intestinal tract, and the liver. Journal of Nutrition 124(1 Suppl):144S–148S.PubMed ↗
In mice, a nucleotide-free diet was associated with weaker signs of cell-mediated immunity. Infants who were fed breast milk or nucleotide-enriched formula showed higher natural killer cell (NK cell) activity at two months of age than infants fed non-enriched formula.
Immune Responses to Nucleotide-Enriched Infant Formula
Gutiérrez-Castrellón P et al. (2007). Immune response to nucleotide-supplemented infant formulas: systematic review and meta-analysis. British Journal of Nutrition 98 Suppl 1:S64–S67.PubMed ↗
An analysis of 15 studies showed that infants fed nucleotide-enriched formula produced more antibodies after vaccinations against Hib, diphtheria, and polio than infants fed breast milk or conventional formula. The authors cite better immune system maturation and fewer cases of diarrhea as the main benefits, with greater effects observed at higher doses.
ⓘClassification: The strongest evidence on this topic, but limited exclusively to infants.
Nucleotides in the Immune and Digestive Systems
Hess JR, Greenberg NA (2012). The role of nucleotides in the immune and gastrointestinal systems: potential clinical applications. Nutrition in Clinical Practice 27(2):281–294.
PubMed ↗Review
The authors describe dietary nucleotides as conditionally essential when the body's need for them is increased, such as during growth, injury, or infection.
Context: The authors themselves consider the claims regarding the specific benefits of individual nucleotides to be limited.
2
GROUP 2 · STUDIED IN HUMANS
Studies involving humans
Randomized studies involving infants and adult athletes.
9Studies
5with infants
4with athletes
The higher the level, the greater thesignificance. Click on a level to jump to the studies.
TARGET AUDIENCE
Infants
5 StudiesNucleotides, Diarrhea, and the Immune Response
Yau KI et al. (2003). Effect of nucleotides on diarrhea and immune responses in healthy full-term infants in Taiwan. Journal of Pediatric Gastroenterology and Nutrition 36(1):37–43.DOI ↗
The study examined how nucleotides in infant formula affect diarrhea and the immune response in healthy infants in Taiwan.
Ribonucleotides and Antibody Production
Schaller JP et al. (2004). Effect of dietary ribonucleotides on infant immune status. Part 1: Humoral responses. Pediatric Research 56(6):883–890.PubMed ↗
The study examined how ribonucleotides in infant formula affect antibody production following vaccinations.
Nucleotides and Immune Function in Infants
Carver JD, Pimentel B, Cox WI, Barness LA (1991). Effects of dietary nucleotides on immune function in infants. Pediatrics 88(2):359–363.PubMed ↗DOI ↗
The study compared the immune function of infants fed breast milk, nucleotide-enriched formula, and conventional formula. Among other things, the activity of natural killer cells was higher in infants fed nucleotide-enriched formula.
Growth and Immune Function in Infants
Hawkes JS, Gibson RA, Roberton D, Makrides M (2006). Effect of dietary nucleotide supplementation on growth and immune function in term infants. European Journal of Clinical Nutrition 60(2):254–264.PubMed ↗DOI ↗
Healthy infants were given formula containing 33.5 mg/L or 10 mg/L of nucleotides. After 7 weeks, there were no differences in growth or immune markers. After 7 months, antibody levels against the tetanus vaccine were higher in the nucleotide group; there was no difference in antibody levels against Hib.
Classification: The authors themselves describe the improvement as modest.
Vaccine Responses in Infants Over One Year of Age
Pickering LK et al. (1998). Modulation of the immune system by human milk and infant formula containing nucleotides. Pediatrics 101(2):242–249.PubMed ↗DOI ↗
Healthy infants were given formula with or without nucleotides for one year; a third group was breastfed. In the group receiving nucleotides, antibody production following vaccinations against Hib and diphtheria was higher. Breastfed infants, on the other hand, had higher antibody levels against polio.
TARGET AUDIENCE
Adult Athletes
4 StudiesImmune markers after intense exercise in the cold
Riera J, Pons V, Martinez-Puig D, Chetrit C, Tur JA, Pons A, Drobnic F (2013). Dietary nucleotides improve markers of immune response to strenuous exercise in a cold environment. Journal of the International Society of Sports Nutrition 10:20.DOI ↗
Athletes took a nucleotide supplement or a placebo for four weeks and then underwent strenuous exercise in cold conditions. After the exercise, lymphocyte counts decreased in both groups, but recovered more quickly in the group taking nucleotides. The lymphocytes’ ability to proliferate was also higher in the nucleotide group.
Sublingual Nucleotides and Immune Parameters
Ostojic SM, Obrenovic M (2012). Sublingual nucleotides and the immune response to exercise. Journal of the International Society of Sports Nutrition 9:31.DOI ↗
Healthy men between the ages of 20 and 25 took 50 mg of nucleotides sublingually or a placebo for 14 days. In the nucleotide group, immunoglobulin A levels in the blood, as well as the number and activity of NK cells, increased, and the decline in antibodies in saliva following exercise was less pronounced.
Conclusions: Small group, consisting only of young men, and the nucleotides were taken sublingually rather than swallowed.
TRANSPARENCY
Studies in which Dr. Peter Köppel participated
2 Studies
Dr. Peter Köppel
Developer of nucleotide raw materials, Pro Bio
The following two studies were conducted in collaboration with Dr. Peter Köppel (Pro Bio), who developed the nucleotide raw materials used in them. We are pointing this out so that you can evaluate the results for yourself.
Learn more about Dr. Köppel →Stress Hormones and the Immune Response During Intense, Short-Term Stress
McNaughton L, Bentley D, Koeppel P (2007). The effects of a nucleotide supplement on the immune and metabolic response to short-term, high-intensity exercise performance in trained male subjects. Journal of Sports Medicine and Physical Fitness 47(1):112–118.PubMed ↗
For 60 days, participants received a nucleotide supplement, a placebo, or nothing, and completed a two-minute maximal exercise test. After the treatment period, levels of the stress hormone cortisol following exercise were lower in the nucleotide group than in the other two groups. Salivary IgA levels were also measured.
Conclusions: Small study; the developer of the raw materials is a co-author.
Salivary IgA and Cortisol During Endurance Exercise
McNaughton L, Bentley DJ, Koeppel P (2006). The effects of a nucleotide supplement on salivary IgA and cortisol after moderate endurance exercise. Journal of Sports Medicine and Physical Fitness 46(1):84–89.
PubMed ↗The participants rode a bicycle for 90 minutes before and after 60 days of supplementation. Salivary IgA levels decreased after exercise in both groups. In contrast, post-exercise cortisol levels in the nucleotide group were significantly lower than in the placebo group after the supplementation period.
Classification: Very small groups of 7 people per group; the co-author is the developer of the raw materials.
3
GROUP 3 · BASIC RESEARCH
Animal studies
How nucleotides might function in the body.
iContext: Animal studies indicate possible mechanisms of action. It remains to be seen whether the results can be applied to humans.
3Studies
Miceas a model
1986–1997Time period
The higher the level, the greater thesignificance. Click on a level to jump to the studies.
Nucleotides and Age-Related Changes in the Immune System
Ameho CK et al. (1997). Modulation of age-related changes in immune functions of protein-deficient senescence-accelerated mice through dietary supplementation with a nucleoside-nucleotide mixture. British Journal of Nutrition 77(5):795–804.PubMed ↗
In mice that age rapidly and have a protein deficiency, the proliferation of immune cells in the thymus and spleen was greater when treated with a nucleoside-nucleotide mixture than when not treated with it.
Classification: Animal study. Shows a possible link to aging, but says nothing about humans.
Low-Nucleotide Diets and Bacterial Infections
Kulkarni AD et al. (1986). Influence of dietary nucleotide restriction on bacterial sepsis and phagocytic cell function in mice. Archives of Surgery 121(2):169–172.PubMed ↗In this study, mice whose diet lacked nucleotides were more susceptible to infection with Staphylococcus aureus, and their phagocytes were less effective than those of mice whose diet contained nucleotides.
Classification: Animal study. Whether
Nucleotides in Cases of Malnutrition
Pizzini RP et al. (1990). Dietary nucleotides reverse malnutrition and starvation-induced immunosuppression. Archives of Surgery 125(1):86–90.
PubMed ↗
In mice whose immune systems had been weakened by starvation or protein deficiency, the addition of nucleotides restored immune responses more effectively than calories and protein alone.
Classification: Animal study conducted under conditions of deficiency; results are not applicable to healthy humans.
STATE OF RESEARCH
What Studies on Nucleotides and the Immune System Show— and What They Don't
Nucleotides in infant formula have been studied most extensively: A meta-analysis of 15 studies found improved antibody responses following vaccinations. In adult athletes, small, placebo-controlled studies showed that immune markers such as lymphocytes or IgA remained more stable after intense exercise. Animal studies provide insights into the mechanisms involved. Whether nucleotides protect healthy adults from infections in everyday life has not yet been investigated.
Current State of Research: October 2026
01
In an animal model
Animal studies
Demonstrate that a deficiency in nucleotides can weaken the immune system. Not directly applicable to humans.
02
Infants
Well-researched
Many randomized trials and a meta-analysis show better immune responses with nucleotide-enriched food.
03
Adults
Initial studies
Small studies involving athletes show more stable immune system levels after intense exercise. There is a lack of large-scale studies in real-life settings.
Our Topics
You should read this, too
Discover what research shows about nucleotides in four areas.
Intestines & Immune System
All StudiesOverview by Topic→gut health
How Nucleotides Are Related to the Intestinal Mucosa and the Microbiome, and What Studies Show on This Topic.
Read more →Training & RecoveryMuscles and Sports
What researchers have studied regarding training, recovery, and nucleotides in athletes.
Read more →New: Study Involving HumansAging HealthilyLongevity
How the immune system changes with age and what role nucleotides play in studies.
Read more →When the Immune System OverreactsAllergies
What research on nucleotides and excessive immune responses is investigating.
Read more →Good to Know
Frequently Asked Questions
Do Nucleotides Strengthen the Immune System?
It’s hard to say for sure. In infants, many studies have shown that nucleotide-enriched food is associated with better immune responses to vaccines. In adults, there are small studies involving athletes in which certain immune markers appeared more stable after intense exercise. Whether this provides protection against infections in everyday life has not been proven.
Why do immune cells need nucleotides?
During an immune response, immune cells multiply rapidly. For each new cell, the DNA must be copied, and this requires nucleotides. Researchers believe that the demand for nucleotides increases during such phases.
What is immunoglobulin A (IgA)?
IgA is an antibody found primarily on mucous membranes, such as those in the mouth, the respiratory tract, and the intestines. In sports studies, it is often measured in saliva because its levels temporarily drop after very intense exercise.
What are NK cells?
Natural killer cells are part of the innate immune system. They recognize and attack abnormal or virus-infected cells without the body needing prior exposure to the pathogen.
Why has there been so much research on babies?
Breast milk naturally contains nucleotides. Researchers therefore sought to determine whether infant formula should also be fortified with them. This is how much of our current knowledge was gained.
What is a meta-analysis?
A meta-analysis synthesizes the results of many studies on a single question. This reveals whether an effect is confirmed across multiple studies, rather than in just a single study. That is why it is considered particularly meaningful.
Are there any studies using Dr. Peter Köppel's nucleotide raw materials?
Yes. Two studies involving athletes were conducted in collaboration with Dr. Peter Köppel, who developed the nucleotide raw materials used in the studies. You can find them on this page in the section titled “Studies Involving Dr. Peter Köppel,” along with a note explaining his role.
For whom are nucleotide supplements not suitable?
They are not recommended—or should only be used after consulting a doctor—in cases of gout or elevated uric acid levels, yeast allergies, autoimmune diseases, after organ transplants, when taking immunosuppressive medications, during pregnancy and breastfeeding, and when taking medication on a regular basis.