Bios Act Complex
Food supplement based on Alphalactalbumin and Hydrolyzed Casein, the noble parts of whey and milk. As of today, the new formulation with Palmitoylethanolamide (PEA) is available.
Alphalactalbumin (ALAC)
ALAC is a whey protein particularly present in human colostrum.
Colostrum replaces the umbilical cord in providing antibodies and growth factors, but it has an additional action compared to the umbilical cord: teaching the newborn to produce them independently.
Colostrums are speciesspecific; human colostrum is the most different from others, as humans are the only mammals born with an immature brain. While the primary action of other colostrums is to activate bone growth, the human one aims to complete brain maturation through intestinal actions.
The first example of the gutbrain axis.
The composition of human milk differs from that of cow’s milk: it has a higher protein content and a different whey protein composition. Human colostrum contains 27% ALAC, compared to only 4% in bovine colostrum, and does not contain Betalactoglobulin.
A primary action of colostrums is to activate the digestive system, which has never functioned during fetal life. The role of ALAC in these actions is well documented in the literature.
Important actions, since the discovery of taste receptors not only on the tongue but distributed throughout the digestive system makes us understand that its main role is not to nourish us, but to protect the environment where the microbiota primarily lives: the colon.
Actions of ALAC on the digestive system
Stimulates mucus production¹;
• Stimulates mucin production, which makes mucus gelatinous, preventing pathogen access;
• Stimulates both acid production by proton pumps and bicarbonate production, thus being able to restore a correct gastric luminal pH.
Thanks to its specific actions on the digestive system, ALAC has a protective effect against alcohol or stressinduced ulcers². In a dosedependent manner, it protects the stomach from alcohol or stressinduced ulcers, up to complete protection.
This result is achieved, in part, by stimulating a thicker protective mucus layer, and, on the other hand, by enhancing the repair mechanisms of damage caused by alcohol or stress.
Confirming that tissue damage (ulcers) is not so much due to the aggressiveness of alcohol or stress, but to a reduced capacity to protect ourselves (mucus) and to repair the damage suffered, through the inflammatory response.
¹ Ushida Y, Shimokawa Y, Toida T, Matsui H, Takase M. Bovine alphalactalbumin stimulates mucus metabolism in gastric mucosa. J Dairy Sci. 2007 Feb;90(2):5416.
² Matsumoto H, Shimokawa Y, Ushida Y, Toida T, Hayasawa H. New biological function of bovine alphalactalbumin: protective effect against ethanol and stressinduced gastric mucosal injury in rats. Biosci Biotechnol Biochem. 2001 May;65(5):110411. doi: 10.1271/bbb.65.1104. PMID: 11440124.
ALAC in the inflammatory response
ALAC restores a correct inflammatory response³, which is characterized by the cytokine cascade, initially discovered for its repair mechanisms. The first cytokines to arrive at the damaged tissue are the proinflammatory ones, e.g., IL1, which cause further necrosis; then, the second ones to arrive, the antiinflammatory ones, go on to rebuild. While we are always able to produce the first ones, we produce the second ones effectively only if there is a high biodiversity of the intestinal microbiota; we have called this type of inflammatory response chronic, lowgrade inflammation.
Today, we know that cytokines are the operational arm of the microbiota through which it performs its control functions over organ function, including the immune system which recognizes and manages viruses with cytokines, and vital parameters. If the effective second cytokines do not arrive, the first ones persist to highlight the problem and the IL1ra (which blocks IL1)/IL1 ratio decreases.
In a dosedependent manner, ALAC increases this ratio, thus restoring the production of cytokines capable of rebuilding, regenerating and controlling.
³ Bovine milkderived αlactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfatetreated mice. Yamaguchi M, Takai S, Hosono A, Seki T. Biosci Biotechnol Biochem. 2014;78(4):6729.
Actions of ALAC on the microbiota
ALAC associated with a highfat diet improves microbiota composition and increases cerebral synthesis of neuropeptide Y (NPY), which is the electrician that repairs the brain.
It has also been defined as an endogenous antiepileptic, due to its actions in controlling brain activity, useful not only for epilepsy⁴.
⁴ Boscaini S, CabreraRubio R, Speakman JR, Cotter PD, Cryan JF, Nilaweera KN. Dietary αlactalbumin alters energy balance, gut microbiota composition and intestinal nutrient transporter expression in highfat dietfed mice. Br J Nutr. 2019 May;121(10):10971107. doi: 10.1017/S0007114519000461. Epub 2019 Mar 5. PMID: 30834845.
Hydrolyzed Casein
Hydrolyzed Casein is obtained by hydrolysis of αs1Casein with pepsin; it contains αcasozepine, a peptide composed of ten amino acids, derived from tryptic hydrolysis of bovine casein, which has anxiolytic properties similar to benzodiazepines.
Preclinical studies indicate that both pure αcasozepine and Hydrolyzed Casein play an important role in improving responses to anxiety and stress conditions.
In rodents, anxiety leads them to try to bury objects considered aggressive, to prefer closed spaces over open ones, or shaded areas rather than illuminated ones.
Both Hydrolyzed Casein and αcasozepine, by reducing anxiety, improve these behaviors. Results similar to those obtained with ALAC, not only with intraperitoneal or intravenous administration, but also with low repeated oral doses over time.
Clinical studies show how Hydrolyzed Casein, taken orally, produces significant improvements in treated subjects compared to the placebo group in physiological variables related to stress, such as systolic and diastolic blood pressure together with heart rate⁵.
In a randomized doubleblind study, a significant reduction in systolic pressure was obtained in highly stressed women after 30 days of treatment⁶.
A randomized, doubleblind, crossover, placebocontrolled study showed, after 30 days of intake, an improvement in stress symptoms, such as anxiety, sleep or general fatigue.
In subjects who presented the highest stress symptoms, Hydrolyzed Casein was effective in improving cardiovascular, digestive, intellectual, emotional and social problems.
Similarly, a significant decrease in anxiety/sleep symptoms, as observed by comparing the mean scores of all rating scales, was obtained in a study of 100 outpatients with anxiety/sleep disorders.
On burnout syndrome (workrelated), the administration of Hydrolyzed Casein produced significant reductions in the characteristic symptoms of this syndrome, measured with different rating scales.
These studies indicate a powerful anxiolytic profile for Hydrolyzed Casein, even after oral administration, similar to diazepam but without the typical side effects of benzodiazepines.
Hydrolyzed Casein does not present the side effects commonly observed in the therapeutic use of benzodiazepines.
⁵ Messaoudi et al. (2005) ⁶ Lanoir and colleagues (2002)
6 Lanoir e colleghi (2002)
Palmitoylethanolamide
Neuroinflammation
PEA combats neuroinflammation by reducing the activity of mast cells and glial cells (microglia and astrocytes) and modulating immune responses in the central nervous system, often via the PPARα receptor.
When administered as a supplement, it primarily reduces neuroinflammation through the following mechanisms:
Glial cell modulation: PEA prevents the hyperactivation of microglia and astrocytes, which are the main immune cells of the brain. The hyperactivation of these cells is the basis of chronic neuroinflammation.
Mast cell stabilization: it inhibits mast cell degranulation, blocking the release of proinflammatory chemicals that can cause nerve sensitization and pain.
Receptor activation: PEA activates the peroxisome proliferatoractivated receptor alpha (PPARα), which reduces the expression of inflammatory genes and the production of proinflammatory cytokines (such as TNFα and IL1β).
Endocannabinoid system support: although PEA does not bind directly to classical cannabinoid receptors (such as CB1 or CB2), it enhances the activity of other endogenous cannabinoids and related lipid mediators (such as anandamide) through an “entourage effect.”
Potential therapeutic applications:
Thanks to its antiinflammatory and neuroprotective properties, PEA is being studied in a variety of neurological and inflammatory conditions:
Neurodegenerative diseases: preclinical studies suggest that PEA can help slow the progression of Alzheimer’s disease, Parkinson’s disease and ALS by reducing the accumulation of neurotoxic proteins (such as betaamyloid) and preserving neuronal health.
Chronic and neuropathic pain: PEA is well documented for its ability to alleviate chronic neuropathic pain (such as sciatica or diabetic neuropathy) by reducing both peripheral and central inflammation.
Mood and cognitive disorders: by limiting neuroinflammation, PEA has shown promise in attenuating anxious behaviors, normalizing neurotransmitter imbalances and protecting against cognitive decline.
Conclusions
Both ALAC and Hydrolyzed Casein have produced analogous behavioral results in both experimental and clinical studies.
The reduction in anxiety is due to the reduction in intestinal inflammation, well documented for ALAC, less so for Hydrolyzed Casein.
Palmitoylethanolamide (PEA) also fits into this context as a molecule with antiinflammatory and immunomodulatory activity, capable of modulating mast cells and glial cells, supporting intestinal barrier integrity and contributing to the control of neuroinflammation.
Above all, chronic lowgrade inflammation is now considered the common cause of all pathologies. Our studies on experimental models of intestinal inflammation have led us to understand that different molecules have antiinflammatory actions, but with different mechanisms.
“Putting out” an inflammation using “extinguishers” that use different mechanisms produces a powerful synergistic action.