NuCell IM featured in the article ‘Nucleotides – the building blocks of life’

Functional Sports Nutrition (FSN) is the magazine for the individuals and professionals who are serious about sport, and features all the latest advances in sports nutrition. This July/August 2011 issue includes an article featuring the ground breaking research on the sports recovery supplement, NuCell IM, this article follows:

‘Nucleotides – building blocks of life’.




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[blockquote]“The problem is that foods rich in nucleotides are now rarely on our menu. Meat products from organs such as liver, kidney, intestines and lung are particularly rich sources of nucleotides, but are now rarely eaten.”[/blockquote]


DNA is the substance inside each and every cell that carries our genetic blueprint. As shown by the characteristic diagram, it is made from building blocks called nucleotides. There is a particular need for sufficiently available nucleotides in cells that divide often. This is the case for our immune cells, which have to divide rapidly in order to respond fast enough to an infection. But also the cells lining our digestive tract, called intestinal villi, are frequently replaced and are in of need of nucleotides for repair. The body is able to recycle old nucleotides from worn out cells (the salvage pathway) or to make new nucleotides (by de novo synthesis) from sources such as glucose and glutamine. However, this process is not very energy-efficient; it’s time-consuming and metabolically taxing. Thus, since the body has only a finite capacity to provide its own nucleotides, it is uniquely able to extract them from foods in our diet which contain them in substantial quantities.


Nucleotides and Immunity

In order to stay healthy, it is crucial for our bodies to be able to rapidly respond to special needs and stressful circumstances. For example, when infected with the Flu, millions of viruses invade our body: these need to be destroyed in order to regain normal health. It therefore becomes crucial that the body has the availability of sufficient nucleotides to rapidly and efficiently respond by producing enough new white blood cells to overcome the infection. If the nucleotide supply is insufficient, the Flu viruses will proliferate unhindered, which may lead to more severe symptoms and prolonged illness. Conversely, with enough nucleotides the infection can be quickly counteracted during its initial stages.


As with many other nutrients, the evidence of the effectiveness and importance of dietary nucleotides was first demonstrated in animal nutrition where they are widely used in fish, poultry, pigs, cattle and horses to enhance performance and to intensify and accelerate natural immune response. Nucleotides are not yet considered essential nutrients for humans, but stress, physical exertion, illness, poor diet and the excessive use of antibiotics and alcohol increase their need in order to facilitate timely and effective cell proliferation. Human breast milk is especially rich in nucleotides. Many infant formulas now contain them because studies have shown that babies fed nucleotide-supplemented infant formula experience better growth and development, maintain a healthier immune system, and have increased levels of beneficial intestinal bacteria which reduce gastrointestinal distress.


In adults, advantageous effects were found in markers of immune function: i.e. salivary immunoglobulin-A (sIgA), which is involved in the first defence against coughs and colds. From a more holistic point of view, it is interesting that both innate and acquired immunity need rapid and unhindered cell proliferation for proper functionality. Unfortunately, cells of the immune system lack the potential to synthesise nucleotides themselves. Other cells not capable of producing sufficient amounts of nucleotides include gastrointestinal and blood cells. Importantly, nucleotides do not stimulate innate or acquired immunity, but rather provide the resource for unhindered cell proliferation, gene expression, and response to special environmental and physical challenges. Their universal use and fundamental functionality and efficacy in every living organism make nucleotides a valuable management tool for many stress and health related conditions.


Dietary and Supplemental Nucleotides

Nucleotides have also gained interest in the area of food allergies or sensitivities because the gut and the immune system are dependent on their ready supply to meet the rapid “turnover” of cells. Nucleotides modulate the expression of inflammatory reactions in the intestine. In infants, nucleotides boost the production of Immunoglobulins and increase the tolerance of food. Another outcome, and probably the most interesting one, is the improvement of gut health: nucleotides strikingly increase the length of intestinal villi (shown in Figure 2), the structures in our gut which constitute the enormous surface of our gastrointestinal tract. For instance, the incidence and duration of childhood diarrhoea is reduced when supplemental nucleotides are given. Improvements were also found in patients with irritable bowel syndrome (IBS), a very common gastrointestinal disease.


Intestinal villi

Intestinal villi

The problem is that foods rich in nucleotides are now rarely on our menu. Meat products from organs such as liver, kidney, intestines and lung are particularly rich sources of nucleotides, but are now rarely eaten. Modest vegetarian sources include yeast extract, mushrooms, broccoli and cauliflower. In the light of a widespread tendency to cut down on adequate animal-derived foods and the common low consumption of vegetables, it seems reasonable that our overall intake is substantially lower than in pre-industrialised times and populations where a hunter-gatherer type diet was common. Adding nucleotide-rich foods or taking supplements derived from yeast may improve gut integrity, digestive processes and possibly diminish some food intolerances. It may also be relevant for patients of celiac disease in helping speed up the recovery of the gut villi damaged by a gluten-containing diet.


There are a couple of contraindications for taking nucleotides as supplements: because of its purine content, people who are genetically predisposed, have a history of, or suffer from gout are generally advised not to supplement nucleotides. Furthermore, the strong immune-enhancing effect prohibits the use of nucleotides for sufferers of auto-immune diseases and users of immune-repressive medications.


Nucleotides for Athletes: Improved Recovery and Muscle-to-fat Ratio

Body tissue is constantly catabolised during training and competition and has to be rebuilt. Without prior physical training and concomitant tissue break-down, no muscle build-up, strength enhancement or performance improvements will occur. Furthermore, the more quickly cells are resynthesised after workouts, the faster and better will be the recovery. Tissues or cells with a high turnover rate such as the skin, gut-lining, white and red blood cells, as well as growing and recovery tissues, need a steady resynthesis of DNA and high turnover rate of RNA. Particularly, in phases of intensive training, an additional supply of nucleotides through dietary intake is important. Nucleotides are essential for muscle function in different ways: besides protein synthesis, they improve oxygen transport and reduce the effects of lesions in the intestinal tract and muscles.


Hard physical training is a significant stress factor for athletes with various negative outcomes. For example, the levels of immunosuppressive substances like the stress hormone cortisol increase and thereby reduce the defence forces of our body. As a result, decreased levels of the important immunoglobulin sIgA have been found in athletes prone to physical stress. Nucleotide supplementation for 60 days significantly increased sIgA compared to a placebo. Additionally, in the liver and muscles, lower serum levels of stress indicators like creatinase and lactate deyhdrogenase were found after nucleotide supplementation versus the placebo, demonstrating improved recovery from physical stress.


Regarding lipoprotein metabolism, nucleotides are advantageous for endurance and strength athletes alike. Nucleotides are first transported to the liver where they promote the synthesis of protein instead of fatty acids, thereby optimising the muscle-to-fat ratio. This effect is not only significant for lean muscle build-up, but also for weight management. In conjunction with lipoprotein metabolism, effects of nucleotide supplementation have demonstrated increased levels of (good) HDL-cholesterol.


Dietary nucleotides offer pre-absorptive benefits in that they serve as fuel to the gut flora (e.g. bifidus bacteria), which improves intestinal health and nutrient absorption. Our gut is the organ with the highest immune capacity of the body. Therefore, a sufficient supply of nucleotides reduces the incidence of intestinal infections. Improved gut health is positive on overall health in general. The absorption of all nutrients like amino acids, minerals, vitamins and other micronutrients takes place in the gut.


NuCell IM – a clinically tested nucleotide supplement

For the serious athlete, supplemental nucleotides may constitute the extra building blocks that are needed during times of extraordinary demand, such as during recovery from strenuous exercise or injury and as prophylaxis to prevent or overcome infections. Even the harmful effects on gut flora from antibiotics may be reversed more rapidly. In several studies*, supplemented nucleotides were shown to more rapidly restore reduced hematocrit values (red blood cell counts) which in turn, improved oxygen supply and uptake.


One double-blind study demonstrated reduced cortisol values after 60 days of NuCell IM supplementation compared to the placebo and pre-supplementation, along with improved sIgA levels. Cortisol is a stress marker and its reduction after physical exercise points to reduced exertion and improved recovery. Because cortisol is also a testosterone inhibitor, its reduction is also advantageous for protein synthesis and muscle build-up. As mentioned above, the increased sIgA values indicate a strengthening of the athletes’ immunity. The measured differences on IgA and cortisol were highly significant (p<0.0001) [1] and the results have been confirmed in another publication by the same authors (2).


An unpublished study done by McNaughton et al. with NuCell IM found substantially enhanced (good) HDL-cholesterol of 15% vs. placebo and even a drop in the control group after supplementation for 60 days (see Figure 3). Additionally, slightly lower (bad) LDL-cholesterol levels were measured. Earlier studies on nucleotides examined the influence on immunity with respect to cold and flu symptoms. NuCell IM supplementation for 28 days reduced the symptoms of a common cold or flu infection or secondary infection: painful sinuses, earache, dry mouth, sore throat, muscle aches, and headache (3).


Much potential exists for the use of nucleotides in a sports person‘s supplement regime. By supporting a more rapid turnover of immune, digestive, muscle and blood cells, along with improving anabolic vs. catabolic drive, this “new” type of nutrient can be a real support to the training and recovery processes of a serious athlete.


Figure 3 – Nucleotide supplements increase HDL


*Studies on nucleotides in athletes were undertaken at the University of Bath, with the supplement corresponding to NuCell IM, manufactured by Swiss biochemical company Pro Bio Ltd.



[list type=”3″]

  • 1. McNaughton et al (2006). The effects of a nucleotide supplement on salivary IgA and Cortisol after moderate endurance exercise. J Sports Med Phys Fitness. 46:84-89.
  • 2. McNaughton et al (2007). The effects of a nucleotide supplement on the immune and metabolic response to short term, high intensity exercise performance in trained male subjects. J Sports Med Phys Fitness. 47(1):112-118.
  • 3. Davidson et al (2002). A randomised, double blind placebo controlled Phase II exploratory trial to assess the effect of Nucell® supplementation on perceived symptoms of the common cold and markers of immune function. Queen Margaret University College, Dep. of Dietetics, Edinburgh, Scotland.


Other Nucleotide studies:

[list type=”3″]

  • Grimble, G.K. (1996) Why are dietary nucleotides essential nutrients? British Journal of Nutrition, 76:475-478.
  • Jyonouchi, H. (1994). Nucleotide Actions on Humoral Immune Responses. Journal of Nutrition. 124:138S-143S.
  • Uauy, R. (1994). Nonimmune System Response to Dietary Nucleotides. Journal of Nutrition. 124:157S-159S.
  • Van Buren C.T. (1994). The Role of Nucleotides in Adult Nutrition. Journal of Nutrition. 124:160S-164S.
  • Köppel, P. (2001). The Role of Nucleotides in the Body. Unpublished, Pro Bio, Switzerland.
  • Tanaka et al (1980). Improved Medium für Selective Isolation and Enumeration of Bifidobacterium. Applied and Environmental Microbiology. 40(5):866 ff.



[blockquote]About the Author

Dr. Peter Koeppel has a PhD in Biochemistry and Immunology. He was trained in Biochemistry with a special interest in clinical Immunology at the Institute of Virology at the University of Zürich. He then worked as a researcher in osteoarthritis and osteoporosis in a pharmaceutical company in Basel. Since 1989 he has been involved in producing special additives for human nutrition for ProBio Ltd, laterally becoming the managing director of this company in year 2000.[/blockquote]

Physical & mental stress can compromise immune response

Stress is a worldwide challenge to health and can come from both physical and emotional sources.


Sometimes it comes from extreme conditions like poverty, starvation, persecution, or war. It can also be the result of caring for a sick family member, the loss of a loved one, troubled relationships or being in an occupation that involves a high level of responsibility or danger. Heavy workloads and the challenges of balancing professional and family life are increasingly common factors.


Stress affects the hormone cortisol produced by the adrenal glands. In small quantities cortisol is helpful. It is anti-inflammatory, speeds tissue repair and controls excess immune cell production. However, continued stress raises cortisol levels beyond healthy levels and slows the production of “good” prostaglandins. “Good” prostaglandins support immune function, dilate blood vessels, inhibit “thick” blood and are anti-inflammatory. The slowed prostaglandin production allows for the opposite – inflammation, immune suppression, etc.



Even healthy people with a balanced immune system can go through phases of suboptimal immune function due to situations of overexertion, stress and exhaustion, which make them more vulnerable to infections. In Switzerland e.g. a new survey revealed that 50% of young people suffer stress.


Excessive stress, either physical or mental, has a detrimental effect on the optimal functioning of the immune system. During a period of stress induced raised cortisol, the immune cells nearly disappear from the blood. The part of the immune system most sensitive to increased cortisol levels are the Natural Killer Cells. A non-scientific analogy to this is that playing card that finally tips the balance on the house of cards, bringing everything crashing down.


The diagram below shows how lifestyle stresses influence immune status and the risk of infection.


It shows that moderate stress and exercise generally leads to a high immune status, and consequent low risk of infection. Conversely, very intensive stress and exercise impacts adversely on the immune status, increasing greatly the risk of infection.


Influence of stress on the immune status and the risk of infection



The effect of stress on the immune system is comparable to the effect of exercise on the muscle. An unused muscle will degenerate, a moderately or intense used muscle will strengthen, but very intensive muscle efforts can lead to severe damage of the muscle.


Pioneering research using nucleotides to overcome the effects of stress

Nucleotides are key components in major processes within the body and play key roles in many biological processes. The requirements for nucleotides increase during times of elevated stress, as indicated previously or additionally when recovering from major tissue injury, systemic infection or when liver function is suppressed.


It has been found that the application of a nucleotide free diet significantly suppresses the cellular immunity. In several studies nucleotide supplementation has been shown to reverse the immunosuppression caused by malnutrition and starvation. A trial with race horses revealed that the level of cortisol after an anaerobic test was significantly lower in horses fed on diet supplemented with nucleotides compared to horses fed the non-supplemented diet, with immunity parameters simultaneously improved. In the same trial a significant increase of the liver enzymes was found in the horses supplemented with nucleotides.


Until recently, there has been limited data available on nucleotide supplementation on the immunologic effects and on stress parameters in humans.  This is an area of research that Pro Bio Ltd, Switzerland, along with Nucleotide Nutrition Ltd, have been pioneering. Pro Bio’s exclusive formulation of purified nucleotides has been shown to lower the formation of cortisol and therefore to prevent the decline of the immune system in endurance athletes.


Effects of a nucleotide supplement in trained male subjects on IgA, Cortisol and Lactate after endurance exercise



The aim of this research was to examine the effect of a nucleotide supplement on IgA and Cortisol levels after endurance exercise of young healthy males.


Endurance exercise trials

Prior to the supplementation period, each subject undertook an incremental exercise test to exhaustion on a cycle ergometer to determine VO2max.


On a separate day the subjects completed a prolonged endurance exercise trial. This comprised 90 minutes at a power output (W) representing 60% VO2max.


Analysis of IgA and cortisol

Prior to the to the endurance trial and immediately upon cessation another saliva and a blood sample was obtained. The saliva was analysed for both Cortisol and IgA and the blood for lactate.



After supplementation of nucleotides IgA was significantly (p<0.01) higher after exercise in test persons compared with placebo subjects. The pre-exercise level of cortisol were not significantly different (p>0.11). However, after supplementation of nucleotides cortisol was significantly (p<0.0001) lower after exercise in test persons compared with placebo subjects.


After the exercise the level of lactate was also significantly lower in athletes receiving a nucleotide supplement.



Nucleotides can help reduce cortisol accumulation and therefore reduce stress.



[list type=”3″]

  • Seyle, H. (1975), The stress of life New York, McGraw-Hill
  • Biondi, M. (2001), Effects of stress on Immune function: an overview. In Ader R,
    Felten DL, Cohen N, editors, Psychoneuroimmunology. San Diego (CA):
    Academic press
  • Avitsur R, Stark JL, Sheridan JF. (2001), Social stress induces glucocorticoid
    resistance in subordinate animals. Horm Behav; 39
  • Avitsur R, Powell N, Padgett D Sheridan JF. (2009), Social Interactions, Stress,
    and Immunity. Immunol Allergy Clin N Am; 29
  • Miller GE, Cohen S, Ritchey AK. (2002) Chronic psychological stress and the
    regulation of pro-inflammatory cytokines: A glucocorticoid resistance model.
    Health Psychology; 21
  • Dantzer R, Kelley KW. (1989) Stress and immunity: an integrated view of
    relationships between the brain and the immune system. Life Sci; 44
  • Schedloswki M, Schmidt RE. (1994) Stress and the immune system.
    Naturwissenschaften; 83
  • Avitsur R. (2006) Social Interactions, Stress and Immunity.
    Neurologic Clinics; 24
  • Art T, Votion D, McEntee K, Amory H, Kinden A, Close R, Lekeux P. (1994)
    Cardio-respiratory, haematological and biochemical parameter adjustments
    to exercise: effect of a probiotic in horses during training. Vet Res; 25
  • Vasquez-Garibay E, Mendez-Estrada C, Romero-Velarde E, Garcia-Iglesias T,
    Campollo-Rivas O. (2004) Nutritional support with nucleotides addition favors
    Immune response in severely malnourished infants. Arch Med Res, 35
  • Van Buren C, Rudolph F. (1994) Dietary nucleotides:
    A conditional requirement. Nutrition, 13
  • McNaughton L, et al (2006). The effect of a nucleotide supplement on
    salivary IgA and cortisol after moderate endurance exercise. J Sports Med &
    Phys Fit
    46, 84-8
  • McNaughton L, et al (2007). The effects of a nucleotide supplement on the
    immune response to short term, high intensity exercise performance in trained
    male subjects. J Sports Med & Phys Fit 47:1, 112-119


Sporty types – Train harder and recover faster

There is substantial evidence that over-training (or a large increase in training load and/or a major effort, such as racing a marathon) depresses the immune system. It is well documented that endurance athletes have a higher incidence of colds and other upper respiratory infections as a result.


Prof. Lars McNaughton reported from his immunity and stress study with NuCell®IM, with sportsmen at Bath University; “Nucleotide supplementation, using this concentrated and purified formula, strengthened the immune system, leading to fewer colds and upper respiratory infections, and it lowered the hormonal reaction to stress, meaning lower levels of cortisol.“


This work suggests that a dietary nucleotide supplement may offset the hormonal response associated with demanding endurance activity. Specifically, the body’s reaction to the stress of training may be lessened. The implications are that nucleotide supplementation strengthens the immune system, leading to fewer colds and upper respiratory infections, and that it lowers the hormonal reaction to stress, meaning lower levels of cortisol during and after exercise, and thus to less tissue damage, which in turn permits faster recovery.


Additionally, the participants, who were generally healthy sportsmen, reported:
[list type=”3″]

  • Increased feelings of well-being and better appetites
  • Reduced mood swings
  • Fewer symptoms of cold and flu
  • Enables better quality and longer night’s sleep (an average of one hour extra per night)



Nucleotides are nutritional substances found in every living cell of the body. They help the body to respond rapidly during times of stress and when it is challenged by infection or disease.


Nutritional consultant Nigel Denby comments: “A strong immune system is important to help us fight infection. NuCell®IM contains concentrated forms of nucleotides helping to boost our bodies’ levels which we may not be getting from our diet.”


Nucleotides are commonly found in offal, yeast extracts, fungi, lean meat and fish. Unfortunately, today’s increased intake of processed foods, with reduced amounts of lean meat, and restricted dietary regimes and fads, often leave a deficiency in our diet.