P. R. Patil Institute of Pharmacy, Talegaon (SP).
Cardiovascular diseases (CVD) and diabetes mellitus(DM) are significant global health concerns. They both represent a key public health problem worldwide. Nutraceuticals, defined as food or part of food that provides health benefits, as well as by isolated nutrients and dietary supplements. They have emerged as adjuncts in the management of these conditions. The main aim of this current paper was to examine the impact of nutraceuticals in relation to the management of cardiovascular diseases and diabetes mellitus. The mechanisms by which nutraceuticals exert their effects include improving insulin sensitivity, modulating lipid profiles, reducing oxidative stress, and regulating inflammatory responses highlighting recent advancements, key mechanisms, and future directions, emphasizing the need for well-designed clinical trials to establish standardized guidelines for nutraceuticals use in managing cardiovascular diseases and diabetes mellitus. This article also reviews the evidence supporting the efficacy of various nutraceuticals in preventive medicines and their potential therapeutic benefits..
1.1 Nutraceutical
The term ‘nutraceutical’ was coined from ‘nutrition’ and ‘pharmaceutical’ in 1989 by Dr Stephen DeFelice and the Foundation for Innovation in medicine [1]. A nutraceutical may be a naturally nutrient- rich food such as spirulina, garlic, soy or a specific component of a food like omega-3 oil from salmon. They are also known as medical foods, nutritional and dietary supplements. It ranges from isolated nutrients, dietary supplements, genetically engineered ‘designer’ foods, herbal products, and processed products such as cereals and soups [2]. Nutraceuticals are marketed in concentrated forms as pills, capsules, powders and tinctures either as a single substance or as combination preparations [3]. Ginseng, Echinacea, green tea, glucosamine, omega-3, lutein, folic acid, and cod liver oil are a few common nutraceuticals Hence, they are recognized as beneficial sources of health promotion, especially for prevention of life-threatening diseases such as diabetes, cardiovascular diseases, renal, and gastrointestinal disorders. [5]
1.2 History:
In the early 20th century, significant advancements in public health occurred, such as the addition of iodine to salt in the United States to prevent goitre, a practice that demonstrated the early use of food-based interventions to prevent disease. The term “nutraceutical” was coined in 1989 by Stephen DeFelice, Chairman and Founder of the Foundation for Innovation in Medicine. According to DeFelice, a nutraceutical is "a food (or part of a food) that provides medical or health benefits, including the prevention and/or treatment of disease." However, in its common usage, the term does not have a formal regulatory definition. Nutraceuticals have now become an integral part of the global dietary landscape. Countries like the United Kingdom, Japan, and Canada have recognized nutraceuticals in various forms, from pills and powders to elixirs. In India, nutraceuticals are primarily derived from herbal and botanical raw materials, used to prevent and treat a wide range of diseases. Globally, the role of diet is considered more important than exercise or genetics in achieving optimal health.
This historical journey from the early use of food for medicinal purposes to the modern nutraceutical industry highlights the growing significance of food-based health products in both traditional and contemporary medicine.
1.3 Concept of Nutraceuticals:
In the pharmaceutical development process, it is a requirement to have clinical test results for animal tests and studies and for verification of their therapeutic effects. But in the case of nutrition, there was no verification method for foods in preventing diseases in the past. In recent years however, as food composition has been scientifically proven to cause life style related diseases, and has become a social issue. The nutraceutical items are recognized and deliver wellbeing benefits like alleviating the chance of cancer and heart dis additionally to avoid or treat hypertension, high cholesterol, over the top weight, osteoporosis, diabetes, joint pain, macular degeneration (driving to irreversible visual impairment), cataracts, menopausal indications, a sleeping disorder, decreased memory and concentration, stomach related upsets and obstruction, not to specify cerebral pains; other items are touted as cures for diminishing hair, need of certainty, destitute complexion, varicose veins, liquor addiction, sadness, and dormancy. The concept of Nutraceuticals has begun to be recognized as one of the measures for avoiding such diseases
Nutraceuticals play a significant role in altering and keeping up ordinary physiological work that keeps up sound human creatures. The food products used as nutraceuticals can be categorized as dietary fibre, prebiotics, probiotics, polyunsaturated fatty acids, antioxidants, and other different types of herbal natural foods. These nutraceuticals are used in various diseases such as obesity, cardiovascular diseases, cancer, osteoporosis, arthritis, diabetes, cholesterol, etc. On the whole, “nutraceutical” has to lead to a new era of medicine and health, in which the food industry has become a research oriented sector.
The philosophy behind nutraceuticals Is focused on prevention. Most times it can be used in the context of Dietary supplements and/or functional food.
? Dietary Supplements: These are products designed to complement the diet, containing ingredients like vitamins, minerals, amino acids, herbs, or other natural substances. Unlike pharmaceuticals, dietary supplements are not intended to treat or cure diseases but are aimed at enhancing overall health by filling nutritional gaps.
? Functional Foods: Defined by the U.S. Institute of Medicine’s Food and Nutrition Board, functional foods are any foods or ingredients that provide a health benefit beyond the traditional nutrients they contain. These foods are consumed as part of the regular diet to promote health and prevent disease. They contain active components derived from plant or animal sources that have physiological benefits.
Classification of Nutraceuticals
Nutraceuticals can be classified based on various criteria, such as their source, chemical composition, mode of action, and health benefits. Below is a breakdown of the primary classifications of nutraceuticals:
1. Based on Products Available in the Market
I) Traditional Nutraceuticals:
Traditional nutraceuticals are natural foods that have not been artificially modified. These foods inherently possess active compounds that contribute to health benefits. Common examples include tomatoes, guava, watermelon, and papaya, which contain lycopene, an antioxidant that may help prevent certain cancers, such as prostate and bladder cancer.
Traditional nutraceuticals can be further categorized as:
Herbals:
Proanthocyanidins
(iii) Phytochemicals:
II) Non-Traditional Nutraceuticals:
Non-traditional nutraceuticals are food products that have been artificially enhanced through biotechnology or agricultural breeding. These foods contain added nutritional elements that improve health outcomes.
Non-traditional nutraceuticals can be divided into:
2.The Role of Nutraceuticals In Disease Management:
The role of nutraceuticals in following disease conditions:
2.1 cardiovascular disease (CVDs):
Cardiovascular diseases (CVDs) remain the leading cause of death globally, accounting for a significant proportion of morbidity and mortality worldwide. The development of CVDs is influenced by a combination of non-modifiable and modifiable risk factors, underscoring the importance of both genetic predisposition and lifestyle choices in disease prevention and management.
Non-Modifiable Risk Factors: - Certain cardiovascular risk factors are inherent and cannot be changed.
1. Age: Advanced age is strongly correlated with increased cardiovascular complications.
2. Gender: Men are generally at higher risk for CVDs earlier in life, although postmenopausal women experience a comparable or higher risk.
3. Ethnicity: Certain ethnic groups are predisposed to specific CVD risk factors, such as hypertension and diabetes.
4. Family History: A genetic predisposition to CVDs, particularly when a first-degree relative has been diagnosed at an early age, significantly increases risk.
Modifiable Risk Factors :-In contrast, several risk factors are influenced by lifestyle and can be altered to reduce cardiovascular risk:
1. Dietary Habits: Diets high in saturated fats, trans fats, and added sugars contribute to hyperlipidaemia, obesity, and diabetes, while diets rich in fruits, vegetables, and whole grains offer protective effects.
2. Body Weight: Obesity, particularly central adiposity, is associated with hypertension, diabetes, and metabolic syndrome.
3. Physical Activity: Sedentary behaviour increases cardiovascular risk, whereas regular physical activity enhances cardiovascular health.
4. Smoking and Alcohol: Tobacco use and excessive alcohol consumption are significant contributors to CVDs, promoting hypertension, atherosclerosis, and heart failure.
5. Stress: Chronic stress exposure and poor stress management are linked to increased blood pressure and other cardiovascular complications.
Intermediary Risk Factors
Conditions such as obesity, diabetes, hyperlipidaemia, and hypertension serve as both risk factors and intermediary outcomes of lifestyle factors. These conditions are partially modifiable through interventions targeting diet, physical activity, and medical therapy.
Phytochemicals in Cardiovascular Disease Management: -
Phytochemicals are bioactive compounds derived from plants that play a crucial role in preventing and managing cardiovascular diseases (CVDs). Their cardioprotective effects are mediated through multiple mechanisms, including lipid profile improvement, blood pressure regulation, and antioxidant activity.
1.Plant sterols: These are natural compounds found in vegetable oils, nuts, seeds, legume, fruits, vegetables and grains. E.g. sitosterol, camp sterol and stigmasterol. It should be consumed 150 to 400 mg/day. Stanols are the saturated plant sterols found in avocados, pumpkin seeds, cashews, rice bran etc. Both plant sterols and stanols help to reduce serum cholesterol levels by suppressing intestinal absorption of cholesterol. Hence, sterols are useful in preventing coronary heart diseases. 6. Nuts: Nuts contains mono- and poly-unsaturated fatty acids, dietary fibre, phytosterols, and polyphenols etc. Nuts reduce levels of LDL cholesterols and thus reduce the risk of CVDs.
2.Omega 3 fatty acids: Omega 3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against CVDs. As per various studies it can be predicted that Omega 3 fatty acids reduces platelet aggregation, blood viscosity, plasma fibrinogen levels, PF4, and thromboglobulin and increase capillary flow. Thus, it can be used to treat CVDs. Omega 3 fatty acids reduce triglycerides levels and have antiarrhythmic effects. Various research studies have proved that small intake of fish per week would reduce the risk of nonfatal Myocardial infarction by 27% and death from CVD by 17% as fish contains Omega 3 fatty acids. As per National and international guidelines, person should consume at least 250 mg/day Omega 3 fatty acids for maintenance of good cardiovascular health.
3.Probiotics: Probiotic bacteria inhibit cholesterol synthesis and enhance cholesterol metabolism. This action is due to short-chain fatty acids produced during carbohydrate fermentation carried out by these bacteria. Probiotics reduce total cholesterol, triglycerides and LDL. They act by various mechanisms such as coprecipitation and deconjugation of lipids with bile salts, assimilation of cholesterol into the cellular membrane and with microbes. Probiotics are also antioxidant in nature.
4.Soy Proteins: Soy products are rich in polyunsaturated fatty acids, fibre, vitamins and minerals etc. Soy proteins decrease the micellar content and absorption of lipids. It inhibits angiotensin converting enzyme (ACE) and thereby reduces systolic and diastolic BP. According to one study, it was observed that intake of 30-50 g soy per day, reduce total cholesterol (TC), LDL-C, and TG and enhance increase in HDL-C.
5.Polyphenols: Polyphenols include number of phytoconstituents such as flavonoids, phenolic acids, stilbenes and lignans etc. food like fruits, vegetables, cereal and legumes, and beverages are main sources of phenolic compounds. Polyphenols improve HDL-C levels. Polyphenols act as anti-atherosclerotic agent by decreasing LDI. oxidation; improving endothelial function, increasing nitric oxide release; modulation of inflammation and Improvement of antioxidant status: protection against myocardial ischemia and platelet aggregation.
2.2 Diabetes Mellitus (DM):
Diabetes Mellitus is a complex metabolic disorder associated with developing insulin resistance, impaired insulin signalling and ?-cell dysfunction, abnormal glucose and lipid metabolism, sub-clinical inflammation and increased oxidative stress; It was estimated to affect 2.8% of the worldwide population in the year 2000, and it is expected to affect 4.4% in 2030 due to the population aging and a constant increase in obesity; these metabolic disorders lead to long term pathogenic conditions including micro-vascular and macrovascular complications, neuropathy, retinopathy, nephropathy, and a consequent decrease in quality of life and an increase in the rate of mortality.1?3 Among the multiple risk factors underling the incidence and progression of type 2 diabetes mellitus, diet is the main modifiable factor. An increasing number of epidemiological investigations show that diet rich in foods with high content of phytochemicals, high total antioxidant capacity and polyphenolic compounds may be related to lower risk of diabetes and predisposing factors.4?9 Based on the current understanding of pathophysiology of insulin resistance and type 2 diabetes mellitus, multiple pharmacological and non-pharmacological interventions have been developed with the aim of improving glycaemic control and prevention of diabetes complications; in this area, recently the use of functional foods and their bioactive components have been considered as a new approach in the prevention and management of diabetes and its complications.
Nutraceuticals play a significant role in the management of Diabetes Mellitus (DM). Nutraceuticals are bioactive compounds found in foods, dietary supplements, and herbal products that provide health benefits beyond basic nutrition.
Benefits of Nutraceuticals in DM Management:
1. Antioxidant effects: Nutraceuticals like polyphenols, flavonoids, and omega-3 fatty acids help reduce oxidative stress and inflammation associated with DM.
2. Improved insulin sensitivity: Certain nutraceuticals, such as chromium, cinnamon, and berberine, have been shown to enhance insulin sensitivity and glucose uptake in cells.
3. Blood glucose control: Nutraceuticals like alpha-lipoic acid, vitamin D, and magnesium help regulate blood glucose levels and improve glycemic control.
4. Cardiovascular protection: Nutraceuticals like omega-3 fatty acids, CoQ10, and resveratrol help mitigate cardiovascular complications associated with DM.
5. Anti-inflammatory effects: Nutraceuticals like turmeric, ginger, and omega-3 fatty acids help reduce chronic inflammation, which is a hallmark of DM.
Categories of nutraceuticals and their role in diabetes:
Nutraceuticals are non-specific biological therapies used to promote wellness, prevent malignant processes and control symptoms. These can be grouped into the following three broad categories.15 Nutrients: Substances with established nutritional functions, such as vitamins, minerals, amino acids and fatty acids. Herbals: Herbs or botanical products as concentrates and extracts. Dietary supplements: Reagents derived from other sources (e.g. pyruvate, chondroitin sulphate, steroid hormone precursors) serving specific functions, such as sports nutrition, weight-loss supplements and meal replacements.
1.Vitamins: Vitamin C being antioxidant in nature (ascorbic acid) scavenges reactive oxygen species and thus reduces protein glycation. Vitamin E also has protective action against type 2 diabetes. Biotin (member of B complex) is effective against diabetes. It acts by stimulating liver glucokinase activity, increasing insulin production, and enhancing glucose uptake in muscle cells.
2.Calcium and Vitamin D: Appropriate levels of calcium and vitamin D suppresses secretion of parathyroid hormone (PTH), hence help to conserve insulin sensitivity. improve glucose tolerance and prevent diabetes mellitus. Vitamin D alters the balance between intracellular and extracellular calcium in ? cells thereby decreases insulin resistance and increases insulin secretion. Vitamin D is immunomodulatory and anti- inflammatory agent. It reduces the inflammation of pancreatic islets and decreases the autoimmune insulinitis. Vitamin D deficiency is also observed in obese patients with type 2 diabetes
3.L-carnitine: It is vitamin like compound, present in mammalian plasma mainly in skeletal and cardiac muscles. L-carnitine helps in fatty acid transport across the inner mitochondrial membrane into the matrix for ?-oxidation, detoxification of potentially toxic metabolites, regulation of the mitochondrial acyl-Co A/CoA ratio, and stabilization of cell membranes. It avoids accumulation of short and medium-chain fatty acids in mitochondria. It promotes insulin sensitivity, affects oxidative metabolism of glucose and lowers lipid. L carnitine helps to fight with oxidative stress and insulin resistance of skeletal muscles. Carnitine prevents diabetic ketoacidosis by enhancing break down fatty acids and binding acyl residues.
4.Omega-3 fatty acids: Omega 3 fatty acids supplement lowers triglycerides, VLDL- cholesterol, inflammatory markers and blood pressure. It also avoids insulin resistance. Hence, it is helpful in treatment of type 2 diabetes.
5.CoQ10: As per clinical study it was observed that CoQ10 improves insulin resistance, lowers glucose and fasting insulin levels.
Key Considerations:
1. Consult a healthcare professional: Before adding any nutraceuticals to your regimen, consult with a healthcare professional to ensure safe and effective use.
2. Monitor blood glucose levels: Regularly monitor blood glucose levels to ensure that nutraceuticals are not interacting with medications or affecting glucose control.
3. Quality and purity: Ensure that nutraceuticals are from reputable sources and meet standards for quality and purity.
Nutraceuticals play a pivotal role in the prevention and management of cardiovascular diseases (CVD) and diabetes mellitus by addressing underlying metabolic and inflammatory pathways. These bioactive compounds, derived from natural sources such as plants, marine organisms, and microorganisms, offer therapeutic benefits beyond basic nutrition. Evidence supports the efficacy of key nutraceuticals like omega-3 fatty acids, plant sterols, polyphenols, fibre, vitamins, and minerals in improving lipid profiles, reducing oxidative stress, enhancing insulin sensitivity, and modulating inflammation. While nutraceuticals have demonstrated promise in reducing the burden of CVD and diabetes, their role should be viewed as complementary to conventional therapies, not as standalone treatments. Personalized approaches, guided by clinical evidence and patient-specific factors, can optimize their therapeutic potential. However, the safety, bioavailability, and standardization of nutraceutical formulations remain areas that require further research and regulatory oversight"
REFERENCES
Gaikwad Sejal, Veladi Shravani, Thombare Tanaya, Chaudhari A. R.*, Gabhane K. B., Salode V. L., The Role of Nutraceuticals in The Management of Cardiovascular Diseases and Diabetes Mellitus, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 12, 2749-2757. https://doi.org/ 10.5281/zenodo.14540812