Oral bovine colostrum supplementation does not increase circulating insulin-like growth factor-1 concentration in healthy adults: results from short- and long-term administration studies

Gastrointestinal symptoms including cramps, diarrhea, nausea, and bleeding are commonly reported by long-distance runners and athletes undertaking extreme endurance competitions and are likely to be due to a combination of reduced splanchnic blood flow, hormonal changes, altered gut permeability, and increased body temperature [1‐4]. These athletes are also susceptible to increased incidence of symptoms of upper respiratory tract infections, especially during periods of strenuous exercise training and immediately after competition [5, 6].

Pharmacological options to reduce these problems are limited, particularly in competitive athletics, and there is, therefore, great interest in the use of natural products. One such product, that is already commercially available, is bovine colostrum. Colostrum is the first milk produced after birth and is particularly rich in immunoglobulins, antimicrobial peptides (e.g., lactoferrin, lactoperoxidase), and other bioactive molecules including growth factors such as transforming growth factor-beta and IGF-1 [7]. As an example, IGF1 levels in bovine colostrum are approximately fivefold higher than mature milk [8]. In combination with the milk that is subsequently produced, colostrum is important for the nutrition, growth, and development of the new-born infant and contributes to the immunological defense of the neonate and in eliminating infection and stimulating growth of the neonatal gastrointestinal tract [9]. In adults, randomized clinical trials have shown beneficial effects of oral colostrum supplementation in reducing NSAID-induced and exercise-induced hyperpermeability [10, 11] and reducing the frequency of upper respiratory symptoms of athletes in training [12].

Colostrum is freely available in health food stores and via the internet and is taken by normal subjects to maintain gut integrity, patients with gut-related injuries and athletes to enhance their ability to train successfully. However, the world anti-doping agency (WADA) advises athletes against taking colostrum for fear of causing a rise in levels of IGF-1 in the circulation with resulting doping penalties (https://​www.​wada-ama.​org). In addition, concerns have been raised that if circulatory IGF-1 is raised in response to colostrum supplementation, prolonged administration of colostrum might stimulate malignancy in distant organs such as prostate cancer which is known to commonly express IGF-1 receptors [13].

To address these potential concerns, we now present studies examining the relationship between colostrum ingestion and circulatory levels of IGF-1. These studies comprised: (1) an analyses of changes in plasma IGF-1 levels following short term administration of colostrum; (2) an analyses of changes in IGF-I in stored plasma samples that were collected during two placebo-controlled randomized trials of longer term bovine colostrum supplementation (1 and 3 months, respectively) on immune health that were led by the authors of the present study [14, 15].

We showed that oral consumption of bovine colostrum (20-40 g/day), either acutely (1–4.5 h post-ingestion) or chronically (4–12 weeks) in healthy adult subjects has no influence on systemic concentrations of IGF-I.

Growth factors, whether produced by purification or using recombinant technology, are increasingly being used for a variety of clinical conditions. Examples include recombinant human insulin for the treatment of diabetes, erythropoietin for renal failure‐induced anemia and interferon for viral hepatitis. The use of such factors for ‘hollow organ’ gastrointestinal conditions is at a more preliminary stage although systemically administered glucagon-like peptide-2 (GLP-2) for the treatment of short bowel syndrome is now a clinically proven, albeit very expensive treatment (estimate $200,000 per quality adjusted life year). In addition to cost, there are concerns that systemic growth factor administration may have unwanted side effects such as tumor progression as many tumors express several growth factor receptors and may also cause other unwanted side effects such as fluid retention.

In parallel with studies of recombinant peptides for gut conditions, there have been several clinical trials examining the potential value of bovine colostrum for gastrointestinal problems. Use of colostrum rather than a single recombinant peptide has the advantages of maintaining potential synergistic activity between the various growth factors within colostrum and that its formulation naturally protects its growth factor activity to reach more distal regions of the gut in an intact biologically active form [16]. These trials suggest that colostrum has clinical value for NSAID-induced gut injury [9], chemotherapy induced mucositis [17] and inflammatory bowel disease [18]. In addition, colostrum may have value for reducing symptoms of infective diarrhea [19], possibly acting through its specific (antibodies) and general antimicrobial constituents such as lactoferrin. Colostrum may also have value as a sports nutritional supplement to reduce the incidence of upper respiratory tract infections during training [15] and to reduce the increased gut permeability that occurs during heavy exercise [20]. Although there is currently insufficient evidence to conclusively establish the value of bovine colostrum to enhance performance, it is being used increasingly by track and field athletes. Of the studies that have been performed, its major value may be in the context of athletes undertaking high-intensity training and in aiding recovery [21].

In addition to its pharmacological advantages, there is currently a demand from the general public for more ‘natural’ types of products, which are usually considered as ‘alternative therapy’, but which can possess potent biological activity. Products such as these are often termed nutraceuticals (from nutrition and pharmaceuticals) [22].

Although there seems to be many advantages of using colostrum at the sports nutrition-functional food interface, two main concerns have been raised, especially if taken for prolonged periods. The first relates to use as a supplement in competitive sports training; The colostrum products used in these studies have been certified by a company (HFL Sports Science UK, Fordham, Cambridgeshire) that has ISO 17025 accreditation for testing sports supplements to control contamination with banned substances to ensure compliance with WADA and has been shown to not contain any banned substances. Nevertheless, because colostrum contains IGF-I, WADA advises athletes against taking colostrum for fear of causing a rise in the levels of IGF-I in the circulation with resulting doping penalties.

Although we are not aware of any clinical data supporting this idea, concerns have also been raised that colostrum might increase the risk of prostate cancer, as prostate cancer cells often express IGF-I receptors and respond to IGF-I administration with enhanced cell proliferation and glucose consumption. However, the pathophysiological situation is more complicated, as administration of IGF-I to noncancerous prostate cells increases basal to luminal differentiation [13].

It is for these reasons that there is much interest in whether circulatory IGF-I increases in subjects taking colostrum. Our initial study attempted to reproduce a standard scenario of a person taking standard doses of colostrum in combination with undertaking moderate exercise, as occurs during sports training. We found no statistically significant differences in plasma IGF-I levels in response to colostrum versus placebo. The second study examined moderate doses of colostrum (10 g twice a day for 4 weeks) reproducing an individual who decides to take a short course of colostrum supplementation and again found no rise in IGF-I levels in either placebo or colostrum group. The third study examined the same 20 g/day dose of colostrum for a prolonged period (12 weeks) and again, no rise was seen.

Our findings support and extend previous work by Coombes et al. who examined changes in plasma IGF-1 in response to 20–60 g per day of colostrum for 8 weeks and found no increase [7]. Similar negative results have been reported by others following ingestion of 20 g or 60 g/day of colostrum or whey, also for 8 weeks [23‐25]. In contrast, Mero et al. reported that colostrum ingestion does increase IGF-I levels [26] although there were methodological and interpretation issues as the only significant effect seen was comparing the change in IGF-1 levels from baseline, due to the placebo arm falling by 18 ng/ml and the colostrum-treated group increasing by 28 ng/ml) [26]. These changes, therefore, seem to reflect physiological variability of IGF-I levels rather than a change due to colostrum ingestion, a conclusion supported by our results from our study 1. In addition, the Mero study [26] used glucose as the placebo rather than a protein containing control as used by other groups. This is important in interpreting their results, as higher protein intake is associated with increased endogenous IGF production [27].

Additional evidence against ingested IGF- I reaching the circulation intact comes from studies examining the effect of orally administered ¹²⁵I labeled IGF-I on blood IGF-I [28]. These showed that virtually all the ¹²⁵I present in the bloodstream was in a digested fragmentary inactive form. This suggests that any change seen in IGF-I levels would be more likely to be due to changes in intrinsic production rather than due to absorption of colostrum derived IGF-I.

In summary, we conclude that ingestion of standard doses of colostrum (20–40 g/day) in healthy adult subjects does not result in an immediate or long-term increase in circulating IGF-I levels. This lack of effect is probably due to the digestion of the IGF-I by intestinal digestive enzymes. These findings provide additional support for the safety profile of colostrum ingestion in populations that can benefit from the favorable effects of colostrum on gastrointestinal and respiratory health.