Evidence Based
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Health Benefits of Dietary Nucleotides: + Side Effects

Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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You are what you eat – there may be more truth to the phrase than we realize. Nucleotides are organic molecules found in most of the foods that we eat. Our body then uses these nucleotides to build our DNA. Can certain people benefit from nucleotide supplements? Read on to learn about the potential health benefits and the evidence behind them.

What are Nucleotides?

Definition

Nucleotides are organic compounds that are essential in all living organisms. They act as building blocks for DNA and RNA, which contain all of our genetic information.

Nucleotides also play a critical role in metabolism and energy. They transport energy in the form of ATP to power different parts of the cell. This energy is used to create new proteins, cells, and other vital components [1+].

Dietary Requirements

There are several different ways we obtain nucleotides. The primary source is from our own bodies. The human body naturally produces nucleotides by either creating them from scratch or salvaging parts from cells [2].

Food is another important source of nucleotides. They are naturally found in meats, fruits, and vegetables. Foods that have high cell density (organ meats, fish, and seeds) contain the highest nucleotide levels [2+].

Nucleotide supplements are also available. However, these supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

Normally, we receive all the nucleotides we need from our body and diet. Limited studies suggest that we may need additional nucleotides when our bodies are stressed – possibly from infection, injury, or during rapid growth. The evidence is still insufficient to support supplementation in these instances [2].

Some scientists hypothesize that areas in the body that experience a high turnover of cells may benefit the most from nucleotides. Cells in the immune system, liver, and gut tend to have very short lives and new cells must be constantly made. This results in a high demand for nucleotides in these areas of the body, at least in animal experiments. Human data are lacking [3].

Few studies have explored the purported benefits of nucleotide supplements. Anecdotally, nucleotides improve the immune system and repair cells in the liver and gut. Clinical trials are needed to verify these claims [1+, 2].

Snapshot

Proponents

  • Naturally found in food
  • Claimed to boost the immune system
  • May support liver and gut health
  • May reduce the stress response from exercise

Skeptics

  • Not well studied in humans
  • Long-term safety and side effects unknown
  • May increase uric acid levels
  • Effects of specific nucleotides mostly unexplored

Nucleotide Building Blocks

Each nucleotide consists of 3 main parts: a sugar molecule, a nitrogen-containing base, and a phosphate group [4+].

The sugar molecule acts as a backbone for the nucleotide. Depending on the chemical structure of the sugar molecule, it is classified as either ribose or deoxyribose. Ribose is used to build RNA, while deoxyribose is used in DNA [4+].

Attached to one side of the sugar molecule is a phosphate group. The phosphate group helps link the sugar molecule to other nucleotides, allowing them to form long chains. Phosphate groups can also provide energy when multiple ones are attached [4+].

The nitrogen-containing base is attached to the other side of the sugar molecule. In our DNA there are 4 types of nitrogen bases, represented by the letters A, T, C, and G. These different bases form the genetic language of our DNA. We have all the same bases in our RNA as in our DNA except for one: in RNA, the base labeled as T is replaced by U [4+].

All in all, this gives us 5 bases for nucleotides:

  • A: Adenine (makes adenosine) [5]
  • T: Thymine (makes thymidine) [6]
  • C: Cytosine (makes cytidine) [7]
  • G: Guanine (makes guanosine) [8]
  • U: Uracil (makes uridine) [9]

If there is no phosphate group, the molecule is called a nucleoside (indicated in parentheses above, e.g. adenosine). Basically, scientists say that the body uses these nucleosides only to make nucleotides [4+].

Supplements can contain a mix of all 5 nucleotides if they’re a DNA/RNA complex. This means that they should have all the following:

  • Adenosine Monophosphate (AMP)
  • Thymidine Monophosphate (TMP)
  • Cytidine Monophosphate (CMP)
  • Guanosine Monophosphate (GMP)
  • Uridine Monophosphate (UMP)

If the supplement is RNA-only, then it won’t have TMP. Some nucleotides like UMP are also sold individually.

How Are Nucleotides Created?

Research reveals that our bodies have two ways of creating nucleotides. The first pathway involves building brand new ones from amino acids. Creating nucleotides through this pathway requires a lot of energy [2+].

The salvage pathway creates nucleotides from other pre-built nucleosides and bases. This method requires far less energy and is preferred by areas of the body that have high nucleotide demands, like the gut [10].

Food is another important source of nucleotides. Our stomachs contain enzymes that break down proteins and cells into nucleotides. We also have enzymes that convert nucleotides to nucleosides, which are better absorbed [11+].

Once nucleotides are created by the body or absorbed from food, they can be used for a variety of functions. Multiple nucleotides can be chained together to form strands of DNA. Nucleotides can also be converted to other forms that help in metabolism and regulation [4+].

Potential Health Benefits of Nucleotides

Insufficient Evidence for:

The following purported benefits are only supported by limited, low-quality clinical studies.

There is insufficient evidence to support the use of dietary nucleotides for any of the below-listed uses. Remember to speak with a doctor before taking dietary nucleotide supplements, which should never be used as a replacement for approved medical therapies.

1) Immune Support

Some scientists think that nucleotides may help support the immune system, where cell turnover is high. Some cells in the immune system live for only 1-3 days, meaning new cells need to be constantly created. Theoretically, nucleotides can provide ready-to-use parts, saving the body time and energy [3+].

Human research on nucleotides and the immune system mainly focused on infants. This is because infants, especially premature newborns, require nucleotides to develop properly. Milk provides most of the nucleotides that babies need, but studies are investigating whether extra supplementation can be beneficial [3+].

The proposed benefits for infants include:

  • Increasing antibodies, T cells, and natural killer cells in the body [12, 13, 14]
  • Reducing diarrhea [14]
  • Promoting the growth of good bacteria [15]
  • Improving vaccine effectiveness [16]

There’s still insufficient evidence to support these health effects, however.

Very few studies have looked at the immune-related benefits of nucleotides in adults. One small study of 20 men examined the effects of strenuous exercise on the immune system. They found nucleotides can increase the level of lymphocytes, a type of white blood cell. Larger trials are needed [17].

2) IBS

One clinical trial of 37 people found that nucleotides may improve IBS (Irritable Bowel Syndrome) symptoms by 4-6%. The authors suggested that nucleotides are most effective for stomach pain and incomplete bowel movement, but these findings have yet to be confirmed in larger trials [18].

3) The Stress Response from Exercise

It’s obvious that exercise has wonderful benefits for our bodies. However, exercise also sets off a stress response that can suppress our immune system [19].

In one study of 20 people, nucleotides reduced cortisol levels after heavy resistance exercise. Cortisol is a hormone that the body releases in times of stress [19].

A different study of 14 men found a similar cortisol-lowering effect of nucleotides after moderate endurance exercise [20].

Larger clinical trials are needed.

Lacking Evidence (Animal Research)

No clinical evidence supports the use of dietary nucleotides for any of the conditions listed in this section.

Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

Liver Function

Our liver performs a variety of key functions including detoxification and metabolism. In fact, the liver is responsible for creating and breaking down the sugars, fats, and proteins in our body. Nucleotides, which also play a role in metabolism, are very active in the liver [21].

Animal studies suggest that a nucleotide-supplemented diet improves the composition of the liver. In one mouse study, a supplemented diet changed the fat and cholesterol content in the liver. In rats, nucleotides lowered lab markers (ALT and AST) that indicate liver damage or disease [22, 23, 24].

Nucleotides are hypothesized to help in cirrhosis, a condition caused by chronic liver injury, but this hasn’t been proven. Based on animal studies, dietary nucleotides may reduce liver scarring and increase liver activity. Human data are lacking [25, 26].

Digestive System Health

The digestive system is another area in the body where cells have a quick turnover. Because our stomach is an acidic environment, the cells in our gut have to be constantly renewed. Several animal studies suggest that nucleotide supplements may assist with this cell rebuilding [1].

Our intestines have special structures called villi that help absorb nutrients. Research shows that nucleotides might promote villi growth, potentially improving nutrient absorption. According to one study, rats that were given nucleotide precursors had 25% larger villi [27, 28].

Nucleotide-supplemented diets are also being researched for helping repair the gut after injury. Based on rat studies, they might help recover the damage caused by malnutrition, organ transplant, and chronic diarrhea. Clinical trials are needed [29, 24, 30, 31, 32].

Growth Promotion

Nucleotides provide essential components that the body needs to build new cells. It may come as no surprise that nucleotides are being researched for promoting growth as well.

Studies suggest that nucleotides can increase growth in rats, fish, and sea cucumbers. All of these animals had better growth and weight gain when supplements were added to their diet. Human studies have yet to be carried out [33, 34, 35, 36]

Lifespan

In the lab, rats live longer when their diets are supplemented with nucleotides. A study suggested that dietary nucleotides may increase the average lifespan of rats and decrease tumor-related deaths. Researchers believe this effect may be due to the antioxidant properties of nucleotides, but proper data are lacking to back up this theory [37].

It’s impossible to translate animal longevity findings to humans, though these studies may give scientists some clues. Nonetheless, many substances that seem to increase lifespan or offset diseases in animals fail to pass clinical trials due to a lack of safety or effectiveness.

Memory and Learning

The brain is another area in the body that requires a healthy supply of nucleotides. Based on one study, dietary nucleotides may help the brain by improving memory. Old and young mice perform better on memory tests when they are given nucleotide supplements [38].

In addition, rats on a nucleotide-supplemented diet were better at learning tasks. The researchers found that these rats metabolize fat in the brain differently. Some scientists hypothesize that this may, in part, explain the improved learning ability. Human studies are needed [39].

Cancer Research

The link between nucleotide intake and cancer development is unclear.

According to one unproven theory, an insufficient supply of nucleotides may negatively impact DNA replication and stability. This DNA instability could potentially allow cancer cells to develop [40].

Scientists are exploring whether nucleosides can repair DNA damage in cells, which might theoretically reduce the transformation of normal cells to cancerous ones [40].

On the other hand, nucleotides are hypothesized to increase cell growth [41]. Hypothetically, this means that their use should be carefully and cautiously considered if a person already has cancer.

Human studies are needed to better understand if dietary nucleotides affect cancer.

Nucleotides Side Effects & Precautions

Currently, research has not evaluated the side effects of nucleotide supplements.

Most clinical trials do not include side effect information. Studies that do include this information didn’t report side effects. Animal studies also reported minimal side effects [14, 42, 23].

Safety

The safety and long-term effects of nucleotide supplements have not been studied.

One possible area of concern is in people who cannot break down nucleotides properly. Uric acid is a possible by-product of nucleotide metabolism. Consuming high amounts of nucleotides can theoretically increase uric acid levels, which could lead to gout or trigger gout flare-ups [2+].

Nucleotides are likely safe when consumed in food.

However, few studies have evaluated the safety, side effects, and drug interactions of nucleotide supplements. Far more research is needed to understand the safety profile of these supplements.

Nucleotides Dosage, Foods & Supplements

Dietary Sources

A healthy diet typically provides about 1-2 g of nucleotides each day. However, it can be difficult to keep track of intake as the USDA does not list the nucleotide content inside food [43+].

Overall, foods with the highest amount of nucleotides are [2+]:

  • Meats in general, but particularly organ meats
  • Fish
  • Fruits and vegetables, especially the seeds

Dosage

As far as nucleotide supplements go, the optimal dose is unknown and can’t currently be established due to a lack of proper clinical data.

In one exercise study of 20 male athletes, a dose of 480 mg per day was used. A different study of IBS patients used a dose of 500 mg that was taken 3 times a day [17, 18].

Studies in infants generally try to mirror the nucleotide content found in milk. Human milk contains about 70 mg/L of nucleotides. In the United States, the maximum amount allowed in baby formula is 16 mg/100 kcal [44, 14, 16, 45+].

Nucleotide supplements are available for purchase in a variety of doses. Doses can range from 100-500 mg, taken 1-3 times a day depending on the manufacturer.

These supplements are available as:

  • Liposomal DNA/RNA complex
  • Capsules or tablets
  • Only uridine (uridine monophosphate or UMP)
  • Adenosine (adenosine monophosphate or AMP)
  • RNA-only complex
  • Nucleotides complex with antioxidant plants, vitamins, and/or amino acids
  • High-RNA, high-protein powders from vegetable greens

Liposomal formulations generally have better bioavailability, but this hasn’t been tested with nucleotides yet [46].

Supplement Reviews & User Experiences

The opinions expressed in this section are solely those of the users, who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfDecode. SelfDecode does not endorse any specific product, service, or treatment.

Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfDecode. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

Users of nucleotide supplements tend to leave positive reviews. Many claim they receive an energy boost. They also appear to be popular for their immune system benefits. Some users like to take nucleotides at the first sign of a cold or flu to prevent infections.

Negative reviews primarily come from users who saw no results when taking nucleotide supplements.

Takeaway

Nucleotides are organic compounds that are naturally found in most of the foods we eat. Our body also produces nucleotides by itself. They are used to create DNA as well as regulate energy.

We get plenty of nucleotides from our diet and body. Researchers are investigating whether newborns or areas in the adult body that experience high cell turnover may benefit from additional nucleotides (such as the immune system, liver, and gut).

There’s still insufficient evidence to support the purported benefits of nucleotide supplements, though.

About the Author

Mathew Eng

Mathew Eng

PharmD
Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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