Functional Foods and Nutraceuticals Biochemical and Safety Insights
Functional Foods and Nutraceuticals Biochemical and Safety Insights
Abstract
In recent years, food and pharmaceuticals have emerged as major players in the field of preventive healthcare. Interestingly,
this modern concept of the role of food is echoed by the wisdom of ancient thinkers. “. . . differences of diseases depend on
nutriments” was emphasised by Hippocrates over 2000 years ago when the correlation between food and diseases was little
to none. His revolutionary insight laid the foundation for future research on establishing food as a prevention against diseases.
This realisation has prompted the introduction of new concepts of ‘Functional Foods’ and ‘Nutraceuticals’ to determine
our approach towards wellness through dietary modifications. With the increase in global interest and emphasis on FFs
and nutraceuticals, understanding their biochemistry and mechanisms is crucial for their effective application. This article
attempts to explore and examine the bioactive compounds in FFs and nutraceuticals and their benefits in disease prevention
and as therapeutics. Moreover, holistic understanding, regulatory limits and safe administration of these nutritive products is
essential for the suitability as well as best utilization.
Functional Foods and Nutraceuticals: Biochemical and Safety Insights Adv Clin Toxicol
Advances in Clinical Toxicology
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approved in 1993 and made headlines in Nature News: “Japan Biochemistry of Bioactive Compounds
explores the boundary between food and medicine” [2].
Bioactive substances provide benefits through complex
Functional foods contain bioactive compounds that physiological interactions between compounds and various
aid in metabolism and other molecular processes. They physiological processes, such as enhancing enzymatic
are introduced as part of a regular diet and may contain activity, antioxidation, and strengthening the immune system.
compounds like polyphenols, fatty acids, carotenoids, and The following are some of the many perks of incorporating
vitamins. They interact with various metabolic pathways nutraceuticals and FFs into a daily regime.
to enhance homeostasis and regulate functioning, thus
preventing diseases. Antioxidant Properties: ROS are free radicals produced
naturally during cellular metabolism. Production of ROS
Nutraceuticals, conversely, are concentrated forms of can increase through UV exposure, smoking and pollution.
bioactive substances extracted from food. In 1989, Dr Stephan Its accumulation over time leads to damage of cells and
L. DeFelice (M.D) coined the term ‘Nutraceutical’ by combining tissue. Excess ROS can cause damage by oxidating bases of
‘nutrition’ and ‘pharmaceutical’. As the term suggests, these nucleic acids and cause mutation. Lipid peroxidation, the
food derivatives are consumed as supplements to provide effect of lipid oxidation, is said to be one of the causes of
therapeutic effect. They are available in various formulations, neurodegenerative diseases like Alzheimer’s and Parkinson’s
such as tablets, capsules, powders, and syrups. According to disease. Furthermore, ROS accumulation also results in
the modern concepts, the personalised nature of nutrition is damage to cardiovascular functioning and triggers cancer
vital in view of tailored dietary recommendations, dependent cell production by promoting metastasis.
on diverse responses to functional elements approaches are
well aligned with hygienic and health goals. These functional Many compounds from FFs and nutraceuticals possess
foods must be prepared, marketed and used in compliance to antioxidant properties. They combat oxidative stress by
regulatory guidelines. neutralising reactive oxygen species by donating an electron
to the free radicals and converting them into more stable, i.e.,
Importance in Modern Health less reactive molecules. Certain enzymes (e.g. glutathione)
reduce ROS by breaking it down to hydrogen peroxide.
A part from the usual medical concerns caused by genetic Antioxidants protect lipids from oxidation [3].
defects and age-linked complications, chronic diseases caused
by poor lifestyle are in prevalence. Diseases like cardiovascular Anti-inflammatory Benefits: Inflammation is an
diseases (CVD) and obesity, which were formerly prevalent in immune response towards invading particles like pathogens,
people of middle to older ages, are now widely observed in damaged cells or other irritations. It aims to protect by
younger kids. Similarly, diseases caused by dietary negligence removing the causal stimulus and initiate healing.
and poor diet are causing chronic disorders, among other
factors like stress and pollution. As a result, medical experts Various cytokines, enzymes and pro-inflammatory
have inclined towards utilising the benefits of FFs and molecules (e.g. histamines and prostaglandins) contribute
nutraceuticals, which lies in their capacity to prevent and to inflammation by promoting vasodilation and increasing
manage various chronic diseases. For instance, bioactive permeability in blood vessels. This allows immune cells and
compounds like polyphenols have been linked to improving plasma proteins to arrive at the site of infection and initiate
CVD by lowering blood pressure Figure 1. inflammation, phagocytosis and tissue recovery.
Misra B and Sharma VP. Functional Foods and Nutraceuticals: Biochemical and Safety Insights. Adv Copyright© Misra B and Sharma VP.
Clin Toxicol 2024, 9(4): 000322.
Advances in Clinical Toxicology
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inflammation. Prostaglandins are produced by the action Neuroprotection and Cognition: Neurodegenerative
of enzymes called cyclooxygenases (COX-1 and COX-2). diseases like Parkinson’s disease and Alzheimer’s are proven
Nonsteroidal anti-inflammatory drugs (NSAIDs), like to have a correlation with oxidative stress, mitochondrial
aspirin, reduce inflammation by targeting COX-2 [4]. Certain damage and neuroinflammation. These factors affect neurons
antioxidants, like sulforaphanes (found in cruciferous and deteriorate them over time, leading to cognitive and
plants), are also known to control inflammation. motor dysfunctions, and memory loss. Bioactive compounds,
which help reduce the above factors, have shown potential in
Modulation of Gut Microbiota: Gut microbiota is known preventing neurodegeneration. Compounds like omega-3 and
to aid metabolism and comprises various microorganisms, curcumin have been reported to be beneficial for cognitive
primarily bacteria, fungi, and viruses. These organisms help health as they provide protection against ROS damage and
break down complex elements (e.g., dietary fibres) that inflammation [6].
are not digested by enzymes. Moreover, these organisms
contribute to the synthesis of various vital vitamins (e.g. Cancer Prevention: When a normal cell undergoes
B12). Some of these organisms are known to synthesise genetic mutation and grows uncontrollably, it gives rise
neurotransmitters like dopamine and serotonin, linking to cancer cells. Some of these cells succeed in evading
metabolism to cognitive health. mechanisms of the immune system and lead to the formation
of tumours. This mutation is triggered by various factors like
A healthy gut biome is essential for the proper functioning inflammation, oxidation and genetic modifications. Defects
of metabolism. The imbalance of these organisms in the in tumour suppressor gene (e.g. TP53), which functions in
gastrointestinal tract leads to a condition called ‘dysbiosis’. apoptosis of cancer cells, prevent it from producing necessary
It is commonly caused by consuming highly processed foods, proteins, leading to uncontrolled growth of cells. Oncogenes
antibiotic usage and infection. It can lead to irritable bowel responsible for cell growth turn into cancer-causing cells
syndrome (IBS), obesity and type 2 diabetes. It can also through genetic faults.
lead to the weakening of the intestinal barrier and lead to a
phenomenon known as ‘leaky gut’, where the permeability Antioxidants help prevent tumour formation by
of the intestine increases, allowing toxins and pathogens to neutralising ROS, which causes DNA damage and genetic
cross the barrier and enter blood flow [5]. instability, leading to mutations. Anti-inflammatory
compounds prevent cytokine formation in neurons involved
Various bioactive can help enhance gut health. Prebiotics in cancer progression [7]. Sulforaphane (present in broccoli)
and probiotics are some of the most prominent and effective can induce apoptosis and is considered for therapy against
compounds beneficial for gut microbiota. Prebiotics contain tumours [8].
non-digestible fibres, which selectively stimulate the activity
of gut bacteria and increase their population. Probiotics Ageing: Ageing is a natural phenomenon influenced by
contain live microorganisms which restore the biome multiple factors, such as genetics, lifestyle, and environment.
balance when consumed in adequate amounts. It is characterised by a decrease in physiological functions
and susceptibility to diseases caused by the accumulation
Cardiovascular Health: Cardiovascular disease (CVD) of cellular damage. Collagen protein is responsible for
refers to a group of disorders that impact the heart and blood structural integrity and is present in skin, tendon, cartilage,
vessels. It is one of the leading causes of. Although various and bone. This protein is degraded over time as a result of
factors, like genetics and environmental factors, influence senescence.
CVD, it is primarily experiencing a rise due to poor lifestyle.
Proper diet and lifestyle can regulate ageing by
The majority of CVDs are caused by high cholesterol, decreasing cellular damage. Bioactive compounds that aid
LDL, and hypertension. These lead to plaque formation, in oxidative stress and inflammation help reduce cellular
narrowing the walls and reducing blood flow. When the artery injury and slow senescence. Telomere metabolism is also
carrying blood to the brain is blocked, it leads to brain stroke. closely related to oxidation status. As a result, antioxidants
Hypertension, or high blood pressure, damages arteries and and anti-inflammatory agents can slow down the shortening
reduces blood circulation. Obesity also increases the risks of of telomeres, which is a hallmark of ageing. Polyphenol
CVDs by increasing blood pressure. Deposition of fat occurs compounds like flavonoids inhibit collagen degradation by
around the heart and blood vessels, which can obstruct blood reducing inflammation. Collagen production can be induced
flow, leading to brain stroke and heart attack. Similarly, insulin by consuming compounds which stimulate fibroblast (cells
resistance developed in an obese individual and diabetic that contribute to collagen production). Geroprotectors like
patient leads to high blood sugar and increased fat deposits metformin (medication for Type 2 Diabetes) are studied in
around arteries. This deems them at high risk of CVDs. geroscience as a possible drug for longevity [9].
Misra B and Sharma VP. Functional Foods and Nutraceuticals: Biochemical and Safety Insights. Adv Copyright© Misra B and Sharma VP.
Clin Toxicol 2024, 9(4): 000322.
Advances in Clinical Toxicology
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Misra B and Sharma VP. Functional Foods and Nutraceuticals: Biochemical and Safety Insights. Adv Copyright© Misra B and Sharma VP.
Clin Toxicol 2024, 9(4): 000322.
Advances in Clinical Toxicology
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Misra B and Sharma VP. Functional Foods and Nutraceuticals: Biochemical and Safety Insights. Adv Copyright© Misra B and Sharma VP.
Clin Toxicol 2024, 9(4): 000322.
Advances in Clinical Toxicology
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Solubility and stability of bioactive compounds is one of In Europe, the European Food Safety Authority (EFSA)
the major problems biotechnologists face. It is a challenge to evaluate claims on FFs and nutraceuticals. Food Safety
dissolve compounds which are prone to sedimentation, are and Standards Authority (FSSAI) ensures the quality of
chemically instable or have low storage periods. Similarly, nutraceuticals and FFs in India.
nutraceutical industries experience issues with drug efficacy.
The efficiency of a bioactive compound changes with a Regulation and Safety
change in its environment. It may prove to be beneficial when
consumed from its source but might fail when consumed as Functional foods and Nutraceuticals are promising
an extract. Scientists proceed through various trials to ensure frontiers in therapy through nutrition. Despite their capacity,
that the efficacy of the bioactive compound as a nutraceutical a critical issue is lack of standardised regulation, scientific
upholds the standard they intend to market. Additionally, validation, counterfeit products, overconsumption and
these industries have to ensure the side-effects and biological consumer awareness. Discrepancies between food and
implications over individuals of all ages, genders and chronic drug category result in variety of quality control standards
conditions since it is an over-the-counter projected to be across nations. Comparative to most nations, FSSAI has more
consumed on a regular basis. stringent regulations [18]. A few key aspects of nutraceutical
regulations in India are:
Infrastructure
• All business operators dealing with FFs and nutraceuticals
The efficacy and safety of FFs and nutraceuticals depend must register with FSSAI and acquire licences based on
highly on the quality of their extraction, processing and different categories based on the scale of operations.
Misra B and Sharma VP. Functional Foods and Nutraceuticals: Biochemical and Safety Insights. Adv Copyright© Misra B and Sharma VP.
Clin Toxicol 2024, 9(4): 000322.
Advances in Clinical Toxicology
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FSSAI set standards for manufacturing, processing and Hypercalcemia is an overdosage of calcium. Excess
packaging to ensure safety. calcium doesn’t get absorbed and either calcify at
• Functional food and nutraceutical products must adhere joints, leading to severe conditions like osteoarthritis or
to strict labelling guidelines that demand ingredient accumulates as kidney stones. A suicidal case of mineral
transparency, nutritional information and recommended toxicity was observed through autopsy. A large quantity of
dosage. iron tablets was ingested as a suicidal attempt, leading to
• Health claims must be substantiated with reliable death after 65 hours. Autopsy showed elevated serum iron
scientific evidence to avoid misleading advertisements. levels and deposition of iron on gastric rugae [22].
• Anti-counterfeit measure is emphasised by FSSAI to
protect consumers from fake products. Prevalent consumption of coffee and tea increases pH
and acidity. When pH drops below a level, acidosis occurs.
Despite the regulations, the availability of counterfeit Alkaline water is a product marketed to deal with this increase
products is jeopardizing consumer safety and damaging in acidity. The underlying adverse effect is an increase in
reputed brands. Variability in active ingredient pH from the normal range, which will cause ‘alkalosis’. It is
concentration, inconsistency in quality and lack of scientific characterised by shortness of breath, arrhythmia, nausea
trials compounds the problems as many side-effects go and numbness, among many other symptoms [23].
unnoticed.
Probiotics are generally safe, but similar to other
It is essential to understand that the quality hallmark by bioactives, its extreme usage will cause bloating and diarrhea.
the council doesn’t guarantee the efficacy of nutraceuticals It can also cause infection and trigger immune responses.
and FFs. Proper storage, health condition and suggested Small intestinal bacterial overgrowth (SIBO) is a condition
dosage are necessary to experience gains of functional caused by excessive growth of gut bacteria. Abdominal pain,
compounds. Storage of supplements and foods as labelled nausea, bloating and vomiting are few of the many symptoms
is necessary to protect them from degradation and maintain of SIBO.
potency. Awareness of diseases caused by nutrient deficiency
intensifies preference for FFs and nutraceuticals, but These problems, although prevalent, can be addressed
discussions over overdosage and its side effects are notably by constructing a multi-faceted system with more clinical
lacking. Consumption of bioactive compounds at labelled trials, improved regulations and increase in public education.
dosage is necessary to receive the proposed benefits. Meanwhile, consumers can rely on medical consultants and
Overdosing bioactive compounds may cause varied side educate themselves on these products and their benefits.
effects. While the severity of side effects caused may vary, its
biochemistry remains unchanged. Current Research and Prospects
Accumulation of ROS is the leading cause of damage in The global functional food market is expected to reach
cells, tissues and organs. Its role in cell signalling is a lesser- $228.79 billion in 2025 from $161.99 billion in 2020, with a
known fact by consumers. Low levels of ROS are necessary compound annual growth rate (CAGR) of 8%. Whereas, the
for normal functioning of biochemical processes. Excessive Indian nutraceuticals market size was estimated at USD 26.87
consumption of antioxidants will lead to loss of ROS- billion in 2023 and is projected to grow at a CAGR of 13.5%
mediated signalling, where it acts as a secondary messenger. from 2024 to 2030. Increasing demand and trend of relying
ROS is produced by immune cells as an ‘oxidative burst’ to kill on FFs and nutraceuticals are driving scientists to conduct
pathogens. Reduction of ROS will adversely lead to increased more comprehensive studies on bioactive compounds.
susceptibility to infections and diseases [19]. Various studies are underway to discover therapeutic effects
of bioactives. Functional compounds are being explored
Hypervitaminosis is a condition caused by overdosage by medical professionals for managing chronic lifestyle
of vitamins. In addition to imparting its benefits, different diseases like diabetes, obesity, CVD, etc. Advancements
vitamins at higher dosages impart varied effects. Pyridoxine for creating technology shaped through machine learning,
overdosage was reported to cause neuropathy in a case particularly artificial intelligence, may aid in creating
report. When examined, self-administration and not personalised nutrition plans derived from real-time data
adhering to dosage resulted in neurotoxicity [20]. and wearable technologies. Currently, FFs and nutraceuticals
are the mode for delivering bioactives for maintaining daily
Hypernatremia is a disorder caused by disturbed nutrition intake. In the future, new delivery systems such as
homeostasis of water and sodium levels. It can cause brain nanoencapsulation and 3D-printed supplements are being
cell shrinkage on acute levels and may lead to pulmonary discussed among bioengineers and biotechnologists. These
edema post 48 hours [21]. new propositions will allow dosage to be more precise and
Misra B and Sharma VP. Functional Foods and Nutraceuticals: Biochemical and Safety Insights. Adv Copyright© Misra B and Sharma VP.
Clin Toxicol 2024, 9(4): 000322.
Advances in Clinical Toxicology
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uptake of bioactive to improve the efficacy of administering how pre-and probiotics affect the gut microbiome and
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The authors declare no conflict of interest.
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Misra B and Sharma VP. Functional Foods and Nutraceuticals: Biochemical and Safety Insights. Adv Copyright© Misra B and Sharma VP.
Clin Toxicol 2024, 9(4): 000322.