BIOACTIVE

1. Interaction
Combining the administration of several bioactives has historically been
viewed as undesirable due to the possibility of antagonistic or unfavorable interactions
between the biologics and potential multidrug resistance, which is particularly
concerning when treating cancer. However, there has been a shift toward using
"similar and independent" agonists, which have a similar overall effect on the body
but work through different routes, given the difficulty of preventing and treating
chronic illnesses. Two bioactive substances may have an antagonistic, synergistic, or
additive relationship.
1.1. Synergistic interactions
Synergism can be described as when two bioactive compounds result in similar
effects within the body that can produce additional effects when used concurrently 1.
Consequently, synergism happens when the combined effect of the two bioactives is
greater than the total of the two effects when given alone. This should not be confused
with potentiation, which occurs when an active molecule's effects are amplified by the
presence of an inactive compound. For example, the results of a study investigating
the synergistic effects of phytochemicals found that extracts of individual bioactive
compounds were not effective in preventing oral cancer, but through consumption of a
multitude of synergistic phytochemicals found within whole foods, a significant
therapeutic effect was noted.2 Once the synergistic relationships amongst bioactive
compounds is determined, more efficient co-delivery NDS can be designed.
1.2. Antagonistic interactions
Antagonistic interaction refers to opposing beneficial and adverse signaling by
a single agent. [1]An example is the interaction between dietary fiber and mineral
absorption; certain fibers can reduce the absorption of minerals like calcium, iron, and
zinc. Dietary fibers have been shown to reduce the absorption of minerals including
calcium, iron, and zinc because they and other related chemicals, like phytate, can
bind minerals in vitro. However, the absorption of magnesium appears to be less
influenced. [2]
1.3. Additive Interactions
Additive interaction is defined as a deviation from additivity of the absolute
effects of two risk factors as originally described by Rothman. 3 An example is the

1Ronald J. Tallarida, (2001), Drug synergism: its detection and applications, Journal of Pharmacology and
Experimental Therapeutics, 298 (3) 865-872; http://jpet.aspetjournals.org/content/298/3/865.abstract
2 Sunira Chandra , Kunal Sah , Anjana Bagewadi , Vaishali Keluskar , Arvind Shetty , Renuka Ammanagi ,
Zameera Naik (2012), Additive and synergistic effect of phytochemicals in prevention of oral cancer,
CC BY-NC-ND 4.0 · European Journal of General Dentistry; 1(03): 142-147
DOI: 10.4103/2278-9626.105354
3 Bo Ding (2014), Chapter Four - High-Throughput Genetic Interaction Study, Between the Lines of Genetic
Code, Genetic Interactions in Understanding Disease and Complex Phenotypes, Academic Press, 978-0-12-
397017-6, pages: 55 - 80, DOI: https://doi.org/10.1016/C2011-0-06985-5
combined effect of multiple antioxidant compounds, such as polyphenols in fruits and
vegetables, contributing to overall oxidative stress reduction. [4]
In addition to the above interactions, there are other interactions as follows
1.4. Nutrient - Nutrient interactions
The links between various nutrients and how they interact with one another
within the body are referred to as nutrient interactions. These interactions are an
important topic of study in the field of nutrition science since they can have a big
impact on general health and nutrition. One example of nutrient interaction is the
relationship between iron and vitamin C. Iron is an essential mineral that is necessary
for healthy red blood cells, while vitamin C helps the body absorb iron. Without
enough vitamin C, the body may not be able to utilize iron effectively, leading to iron
deficiency anemia. [3]
1.5. Competition for Absorption
Research on the interaction between the various dietary components and the
digestion, absorption, and use of certain nutrients has always been an interesting topic.
According to a review of the literature, one important aspect of the environment that
affects how well an animal or human absorbs mineral elements from their intestinal
tract is the chemical form in which the element is combined when it enters the
digestive tract or forms inside the tract itself. Studies have shown that high
concentrations of some trace elements, including copper, zinc, and molybdenum,
negatively impact how well these elements and other members of the trace element
family that are necessary for healthy nutrition are utilized. Elevated levels of
magnesium, phosphorus, and calcium can also influence the necessary level. There is
evidence provided about the mechanisms underlying these interactions as well as the
rivalry between the components that could affect absorption and utilization.
1.6. Pharmacokinetic Interactions
Pharmacodynamic interactions are those in which the xenobiotic or dietary
supplement ingredient alters the reaction to it, but neither of their plasma
concentrations changes. When two xenobiotics have opposing pharmacological effects
or when two xenobiotics with identical pharmacological activity create a decreased
response, pharmacodynamic interactions can occur. Understanding the sites and
mechanisms of biological activity of both substances, as well as predicting whether
appropriate levels are obtained at the sites of action, are crucial for forecasting when a
pharmacodynamic interaction may occur and the clinical outcomes of this interaction.
1.7. Hormonal interactions
Bioactive compounds can influence hormone levels and signaling pathways.
For instance, phytoestrogens in soy products may interact with estrogen receptors,
potentially affecting hormonal balance in the body.
 2. Transformation during processing and preservation
The processing and preservation of foods can have a significant impact on the
bioactive nutrients and compounds present in them. Different techniques can alter the
composition, bioavailability, and overall functionality of these bioactive substances.
Here are some common transformations that may occur during food processing and
preservation:
3. Heat-Induced Changes
Drying is an essential postharvest procedure that lowers the moisture content of
plants in order to dehydrate them. By doing so, the dried plants retain their
organoleptic qualities and avoid chemical oxidation. Additionally, by inhibiting
microbial growth and enzymatic breakdown, the dried plants are preserved and have a
longer shelf life. Because drying is so successful at making handling, transportation,
and storage of food products easier, it is one of the processing methods used to
maintain food quality the most. The most widely utilized technique in the food
industry is traditional convective hot air drying because it is low-cost to implement
and easy to control. However, due to its tendency to oxidize and degrade heat-
sensitive compounds and to frequently alter the nutritional value, flavor, and texture of
the products being dried, hot air drying has a negative impact on critical aspects of
food security, such as environmental sustainability and nutrient quality. Long-term
heating destroys the organoleptic properties and bioactive components in food. The
hot airflow heats the material during convection drying. How hot a substance gets
depends on the temperature differential between its surface and the airflow. In
conclusion, high temperatures during cooking, canning, or pasteurization may lead to
the degradation of heat-sensitive bioactive compounds, such as vitamins and enzymes.
For example, vitamin C is sensitive to heat and may be partially destroyed during
cooking. [8] [9]
4. Oxidation reactions
Exposure to air and light during food processing and storage can lead to
oxidative degradation of certain bioactive compounds, particularly antioxidants like
vitamins A, C, and E, as well as polyphenols. It has long been known that processing
fruits and vegetables reduces their antioxidant content and, as a result, reduces their
bioactivity when compared to their fresh counterparts. [12]
5. Enzymatic Reactions
Cutting or processing fruits and vegetables can expose them to oxygen,
triggering enzymatic browning reactions. According to certain research, heat
processing adversely affects the nutritional and organoleptic properties of finished
goods by considerably lowering the amount of bioactive substances including
vitamins, phenolic compounds, and carotenoids.
 6. pH changes
Changes in pH during processing can affect the stability of bioactive
compounds. For example, vitamin stability is often pH-dependent, and acidic
conditions can lead to the breakdown of certain vitamins, thiamine was significantly
more stable in pH 3 than in pH 6 solutions.
7. Extraction and Solubility
The use of solvents in food processing, such as in the extraction of bioactive
compounds for the production of extracts or concentrates, can alter the concentration
and bioavailability of these compounds.
8. Fermentation
Fermentation processes can lead to the production of bioactive compounds,
such as certain vitamins and bioactive peptides. For example, the fermentation of milk
can lead to an increase in the concentration of certain B-vitamins. Cow's milk is a
good source of most vitamins except ascorbic acid and vitamin B12. The nutritional
value of fermented milk products is assumed to be similar to the milk from which they
are made. However, fermentation may lead to an increased concentration of B-
vitamins, but results reported are contradictory
With increasing demand for more nutritious foods, knowledge of changes in B-
vitamin the content caused by fermentation is important. Lactic acid bacteria in
fermented milk products has been suggested as a possible supplementary source of
vitamins in human nutrition. During fermentation there is a dramatic increase in cell
population representing both colony forming units as well as dormant cells. The
increase continues, though slower, even during storage. The B-vitamins are
components of coenzymes and are extremely important in the metabolism and energy
utilization of the cell and more or less essential for starter cultures used in
fermentation of milk. Starters show various needs and ability to synthesize B-vitamins
in excess.
9. Freezing and Freeze-Drying
Water Removal: Freezing and freeze-drying are preservation methods that
involve removing water from food. While these processes help preserve the nutritional
content, they may also lead to changes in the texture and concentration of certain
bioactive compounds. The presence of air gaps and pores in the porous structure of
dry materials can impact color descriptors, particularly the material's lightness.
Determining the color parameters of dried goods is essential because one of the
primary quality criteria that consumers assess is the product's color. Changes in the
color of dried foods can be an indicator of the undesired thermal degradation of many
bioactive compounds.
10. Irradiation
Radiation Treatment: Irradiation can be used to extend the shelf life of foods by
reducing microbial contamination. While it does not necessarily alter the bioactive
compounds directly, it may affect the sensory attributes and overall quality of the
food.
11. Addition of Preservatives
Chemical Stabilization: The addition of chemical preservatives can help
prevent spoilage and extend the shelf life of foods. However, the presence of
preservatives may interact with certain bioactive compounds, and their impact on
health requires careful consideration.
12. Drying and Dehydration
Removal of Water: Drying processes, such as air drying or sun drying, involve
the removal of water from foods. While these methods help preserve foods, they may
also lead to the concentration of bioactive compounds.

REFERENCE
1. Bo Ding (2014), Chapter Four - High-Throughput Genetic Interaction Study,
Between the Lines of Genetic Code, Genetic Interactions in Understanding
Disease and Complex Phenotypes, Academic Press, 978-0-12-397017-6, pages:
55 - 80, DOI: https://doi.org/10.1016/C2011-0-06985-5
2. Cerna, J., and H. Hrabova. 1977. Biologic enrichment of fermented milk
beverages with vitamin B12 and folic acid. Milchwissenschaft 32:247.
3. Dolezalek, J., and V. Havlikova. 1972. Possibilities of utilization of
propionibacteria in the production of Kefir. Vysoke skoly
chemikotechnologicke v Praze, E 33 Potraviny. Sci. Papers, Inst. Chem.
Technol., Prague E 33.
4. Gorner, F., and V. Oravcova. 1969. Changes in thiamine and riboflavin
contents during yogurt and Gouda cheese fermentation. (Pol'nohospodarstvo
15:825.) Dairy Sci. Abstr. 33 (1971). Abstr. No 1607.
5. Ronald J. Tallarida, (2001), Drug synergism: its detection and applications,
Journal of Pharmacology and Experimental Therapeutics, 298 (3) 865-872;
http://jpet.aspetjournals.org/content/298/3/865.abstract
6. Silva-Espinoza M.A., Ayed C., Foster T., Camacho M.D.M., Martinez-
Navarrete N (2019) The impact of freeze-drying conditions on the physico-
chemical properties and bioactive compounds of a freeze-dried orange puree.
Foods. 9:32. doi: 10.3390/foods9010032.
7. Sunira Chandra , Kunal Sah , Anjana Bagewadi , Vaishali Keluskar , Arvind
Shetty , Renuka Ammanagi , Zameera Naik (2012), Additive and synergistic
effect of phytochemicals in prevention of oral cancer, CC BY-NC-ND 4.0 ·
European Journal of General Dentistry; 1(03): 142-147
DOI: 10.4103/2278-9626.105354
8. Mithun Rudrapal, Shubham J. Khairnar, Johra Khan, Abdulaziz Bin Dukhyil,
Mohammad Azam Ansari, Mohammad N. Alomary, Fahad M. Alshabrmi,
Santwana Palai, Prashanta Kumar Deb, and Rajlakshmi Devi (2022) Dietary
Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases:
Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of
Action, Front Pharmacol, 13: 806470, doi: 10.3389/fphar.2022.806470