Blood Flow and Health

Introduction to Blood Flow

Flowing blood is the distributive life force of the body. Blood flow plays a crucial role in maintaining overall health and supporting the proper functioning of the body [1]. In terms of key functions and benefits; blood flow carries oxygen and allows for the absorption and transport of essential nutrients, such as glucose, amino acids, vitamins, and minerals, to all cells in the body. Cells require oxygen and nutrients to produce energy and carry out their specific functions. Blood flow also helps transport waste products, such as carbon dioxide and metabolic by-products, away from cells and tissues to be eliminated from the body through the lungs, kidneys, liver, and other organs. Blood flow further helps regulate body temperature by distributing heat from internal organs to the skin's surface, where it can be released. This process helps maintain the body's core temperature within a narrow range necessary for optimal function. Blood flow plays a vital role in the immune system's function by transporting immune cells, antibodies, and other components that help defend the body against infections, pathogens, and foreign invaders. Adequate blood flow is essential for wound healing and tissue repair processes. The nutrients and oxygen delivered by blood flow help support tissue regeneration and recovery after injuries or surgeries. Efficient blood flow ensures that all organs receive an adequate supply of oxygen and nutrients needed for proper function. Optimal blood flow to the heart, brain, kidneys, liver, and other vital organs is critical for overall health and longevity. Blood flow to the brain is essential for supplying oxygen and glucose, which are the brain's primary sources of energy. Proper blood flow helps maintain cognitive function, focus, memory, and overall brain health. Healthy blood flow helps prevent the formation of blood clots by maintaining the fluidity of blood and promoting the circulation of platelets and clotting factors. This is essential for reducing the risk of cardiovascular events like heart attacks and strokes. Adequate blood flow to muscles during physical activity provides the oxygen and nutrients necessary for energy production and muscle contraction. Improved blood flow can enhance athletic performance, endurance, and recovery. Ensuring healthy blood flow is essential for overall well-being and can be supported through regular exercise, a balanced diet, hydration, maintaining a healthy weight, managing stress, and avoiding smoking and excessive alcohol consumption. Poor blood flow can lead to various health issues, including cardiovascular diseases, cognitive impairments, and impaired wound healing [2]. Just like the human body needs to move to stay healthy, so too, blood needs to move, or it stagnates into a blood clot.

Measuring and Evaluation of Blood Flow

Measuring and evaluating blood flow is crucial in various fields of medicine, including cardiology, vascular surgery, and neurology [3]. Blood flow can be assessed through the following methods; Doppler Ultrasound is non-invasive test that uses sound waves to measure and visualize blood flow in arteries and veins which can detect blockages, narrowing, and abnormalities in blood flow. The Computed Tomography (CT) Angiography is an imaging technique that provides detailed pictures of blood vessels and their flow patterns, and useful for diagnosing conditions like atherosclerosis, aneurysms, and blood clots. The Magnetic Resonance Angiography (MRA) is similar to CT angiography, MRA uses magnetic fields and radio waves to create detailed images of blood vessels and blood flow, which is particularly valuable for assessing blood flow in the brain and spinal cord. The Angiography is an invasive technique that involves injecting a contrast dye into the blood vessels and taking X-ray images to visualize blood flow in real-time and is commonly used in interventional procedures to treat blockages and other vascular conditions. The Laser Doppler Flowmetry is a technique that uses a laser beam to measure blood flow in small vessels near the skin's surface, that is often used in research studies and to assess microcirculation in tissues. The Positron Emission Tomography (PET) scans can measure blood flow and metabolic activity in tissues and are useful for evaluating conditions like cancer and heart disease. The Intravascular Ultrasound (IVUS) technique involves inserting a tiny ultrasound probe into blood vessels to visualize their walls and assess blood flow, and is commonly used in interventions like angioplasty. By combining these various methods, healthcare professionals can accurately assess blood flow, diagnose underlying conditions, and plan appropriate treatments to improve blood circulation and overall health [4].

Anatomy and Physiology of Blood Vessels

Blood vessels are essential components of the circulatory system, responsible for transporting blood throughout the body [5].The Arteries are blood vessels that carry oxygen-rich blood away from the heart to various tissues and organs in the [6] body. They have thick walls comprising three layers: the tunica intima (inner­most layer), tunica media (middle layer with smooth muscle cells), and tunica externa (outer connective tissue layer). Arteries have a thick and elastic wall that helps maintain blood pressure and reg­ulate blood flow. The Veins carry deoxygenated blood back to the heart from the body’s tissues. They have thinner walls compared to arteries, with less smooth muscle and elastic tissue. Veins also have valves that prevent backflow of blood and assist in returning blood to the heart against gravity. Valves are particularly import­ant in the extremities to maintain blood flow back to the heart. The Capillaries are tiny, thin-walled blood vessels that connect arteries to veins and are the site of exchange of oxygen, nutrients, and waste products between the blood and tissues. Capillaries have a thin sin­gle-cell layer that allows for efficient diffusion of substances, and their extensive network ensures that all cells have access to nutri­ents and oxygen.

Physiology of blood vessels involves various processes to regu­late blood flow, blood pressure, and distribution of blood through­out the body. They include Vasoconstriction and Vasodilation where the smooth muscle in the walls of blood vessels can contract (va­soconstriction) or relax (vasodilation) in response to signals from the nervous system or local factors like oxygen levels or hormones. This mechanism helps regulate blood flow and blood pressure. Blood Pressure Regulation is by arteries which have elastic walls that expand and recoil with each heartbeat, helping to maintain blood pressure. The autonomic nervous system and hormones like adrenaline play a role in regulating blood pressure by altering the diameter of blood vessels. Blood Distribution where the blood ves­sels can regulate blood flow to different tissues and organs based on their metabolic needs. This is achieved through local factors such as nitric oxide and prostaglandins that control blood vessel diameter in response to tissue requirements. Understanding the anatomy and physiology of blood vessels is crucial in diagnosing and treating various cardiovascular conditions like atherosclero­sis, hypertension, and venous insufficiency. By maintaining healthy blood vessels and optimizing their function, overall cardiovascular health can be improved, reducing the risk of cardiovascular diseas­es.

Vascular nerves, also known as nervi vasorum, are the nerves that innervate the arteries and veins in the body. These nerves play a crucial role in regulating the diameter of blood vessels through the processes of vasodilation (widening of blood vessels) and va­soconstriction (narrowing of blood vessels). The control of these processes is essential for maintaining proper blood flow, blood pressure, temperature regulation, and overall homeostasis within the body. Innervation of blood vessels by vascular nerves allows for dynamic adjustments in blood vessel diameter in response to various physiological factors and stimuli. For example: Vasodila­tion-When the vascular nerves signal for vasodilation, the smooth muscle cells in the blood vessel walls relax, leading to an increase in the diameter of the blood vessel. This process allows for increased blood flow and enhanced delivery of oxygen and nutrients to tis­sues. Vasodilation can occur in response to factors such as exercise, a need for increased oxygen delivery, and the body’s response to heat; Vasoconstriction-Conversely, when the vascular nerves stim­ulate vasoconstriction, the smooth muscle cells contract, causing the blood vessels to narrow. Vasoconstriction helps regulate blood pressure, reduce blood flow to specific areas, and conserve heat in the body. Factors like stress, cold temperatures, and the need to re­direct blood flow to vital organs can trigger vasoconstriction. Ac­cording to Filosa et al., [7], the intricate regulation of vasodilation and vasoconstriction by vascular nerves is vital for maintaining op­timal blood flow distribution, tissue perfusion, and overall cardio­vascular function. Dysfunction in vascular nerve signaling can con­tribute to conditions such as hypertension, cardiovascular diseases, and impaired thermoregulation. Understanding the role of vascular nerves in controlling blood vessel tone and function, underscores their significance in the body’s physiological regulation and high­lights the complex interplay between the nervous system and the cardiovascular system in maintaining homeostasis.

Blood Flow and Brain Function

Blood flow is crucial for maintaining proper brain function as it supplies essential nutrients and oxygen to the brain cells. The brain requires a constant supply of oxygen to function optimally. Blood carries oxygen from the lungs to the brain. A decrease in blood flow can lead to a decrease in oxygen delivery to the brain, affecting cognitive function and potentially causing cell damage. Blood also carries glucose and other nutrients to the brain cells. These nutrients are essential for energy production and cellular functions. Insufficient blood flow can result in a lack of nutrients reaching the brain, impacting its ability to perform tasks efficiently. Blood flow helps remove waste products and toxins from the brain. Proper circulation is necessary to flush out harmful substances that can accumulate in the brain and impair cognitive function. Blood flow plays a crucial role in maintaining the optimal temperature of the brain. Changes in blood flow can affect the brain's ability to regulate its temperature, potentially leading to dysfunction. Studying blood flow in the brain is essential for diagnostic purposes. Techniques like Functional Magnetic Resonance Imaging (fMRI) rely on detecting changes in blood flow to specific brain regions to understand brain activity during different tasks or in various states. Disruptions in cerebral blood flow can have serious consequences, such as strokes, transient ischemic attacks (TIAs or mini strokes), and vascular dementia. These conditions can result in significant cognitive impairment due to decreased blood flow and oxygen delivery to the brain. Other instrumentation such as ultrasound Doppler Studies can be valuable to understanding current conditions of vessel blood flow. In summary, adequate blood flow is critical for maintaining optimal brain health and overall body function by supplying oxygen, nutrients, and removing metabolic waste. Disruptions including leakiness in blood flow can have profound effects on cognitive abilities and may contribute to various neurological disorders [8].

Blood Vessel disruptions including leakiness in blood flow can have profound effects on cognitive abilities and may contribute to various neurological disorders and can lead to various complications and sequelae [9]. When blood vessels become leaky, it disrupts the normal flow of blood and the exchange of substances between the blood and surrounding tissues. Common disruptions in blood flow and their associated sequelae includes the increased permeability of Blood Vessels (Vascular Leakage) such as an increased vascular permeability can lead to the leakage of fluid and proteins into surrounding tissues, causing swelling known as edema. Edema can impair tissue function and lead to pain and decreased range of motion. The excessive leakage of fluid from blood vessels can lead to a decrease in blood volume, known as hypovolemia, potentially causing low blood pressure, dizziness, and organ dysfunction.

Impaired Blood Flow (Ischemia) including reduced blood flow can lead to inadequate oxygen delivery to tissues, resulting in tissue hypoxia. This can cause cell damage, organ dysfunction, and, if severe and prolonged, tissue necrosis. Prolonged ischemia (Ischemic Injury) can lead to tissue injury or even infarction (tissue death, gangrene) if blood flow is not restored promptly. This can have severe consequences, such as heart attacks, strokes, and organ failure.

Increased Vascular Permeability due to Inflammation can lead to increased vascular permeability, allowing immune cells and proteins to enter tissues to combat infection or injury. However, excessive or prolonged inflammation can cause tissue damage and contribute to chronic conditions like arthritis and inflammatory bowel disease.

Disseminated Intravascular Coagulation (DIC) such as the Abnormal Blood Clotting is a condition characterized by widespread activation of blood clotting within blood vessels. This can lead to both excessive clot formation and depletion of clotting factors, causing a risk of bleeding and organ dysfunction.

Impaired Lymphatic Drainage leads to disruptions in the lymphatic system, which drains excess fluid from tissues, can lead to a buildup of fluid and proteins in tissues known as lymphedema. This can cause swelling, discomfort, and an increased risk of infection in affected areas.

Managing disruptions in blood flow and addressing vascular leakiness require targeted treatments, which may include medications to regulate vascular permeability, interventions to restore blood flow to ischemic tissues, and therapies to reduce inflammation and support lymphatic drainage. Understanding the complications associated with disruptions in blood flow is crucial for healthcare providers in diagnosing and treating conditions related to vascular dysfunction [10].

The Blood Circulatory System and the Lymphatic System

The blood circulatory system and the lymphatic system are two distinct but closely related systems in the human body that work together to maintain various physiological functions [11]. The blood circulatory system, composed of the heart, blood vessels, and blood, is responsible for transporting oxygen, nutrients, hormones, and waste products throughout the body. The lymphatic system is a network of vessels, nodes, and organs that helps maintain fluid balance in the body, absorbs fats, and plays a significant role in the immune response by filtering foreign particles and pathogens [12]. The two systems are interconnected through fluid exchange. Blood plasma leaks out of the capillaries into the interstitial spaces, providing cells with nutrients and oxygen. This fluid, now called interstitial fluid, is collected by lymphatic vessels and returned to the blood circulation as lymph [13].  The lymphatic system also plays a crucial role in immune function. Lymph nodes, which are distributed throughout the body, filter lymph and capture pathogens, enabling the immune system to respond to infections. The lymphatic system is an essential component of the body's immune response. Lymph nodes contain white blood cells that recognize and destroy pathogens, helping to protect the body from infections.

If an infection occurs, the lymphatic system helps to remove waste and toxins from the affected area, and immune cells produced in the lymph nodes are transported via lymphatic vessels to fight off the infection. Dysfunction in either system can lead to various health issues. For example, problems in the blood circulatory system can result in conditions like hypertension, coronary artery disease, or strokes. Issues with the lymphatic system may lead to lymphedema, an accumulation of fluid causing swelling, or impaired immune function. Detoxifying the lymphatic system can help improve its function and overall well-being. The lymphatic system is responsible for removing toxins, waste, and other unwanted materials from the body. When the lymphatic system is clogged or not functioning efficiently, toxins can build up and impact various bodily functions negatively. Detoxing the lymphatic system involves practices such as drinking plenty of water, eating a healthy diet rich in fruits and vegetables, exercising regularly, dry brushing, massage, and using essential oils known to support lymphatic drainage [14].

Dietary supplements can be a helpful addition to detoxifying the lymphatic system by supporting its function and promoting overall health. Dietary supplement approaches such as found in Protein EnzymeTM detox contains useful ingredients including:  Echinacea, known for its immune-boosting properties, echinacea can help support lymphatic function and overall immune health [15,16];  Burdock Root is believed to have detoxifying effects on the lymphatic system and can help with lymphatic congestion[17,18]; and Red Clover contains compounds that support lymphatic circulation and detoxification processes. A combination of herbs, vitamins, and minerals aimed at promoting toxin elimination and overall lymphatic health; and certain enzymes, such as bromelain as found in pineapple [15,16] and papain as found in papaya [140,141] can aid in digestion and support lymphatic drainage by breaking down proteins and reducing inflammation.

The lymphatic system works closely with the circulatory system, which includes the heart and blood vessels. A healthy lymphatic system helps ensure proper blood flow by maintaining fluid balance throughout the body [19]. When the lymphatic system is detoxified and functioning optimally, it can help remove excess fluids and waste products from tissues, reducing inflammation and supporting better blood flow. Improved blood flow can enhance oxygen and nutrient delivery to cells, improve waste removal, and support overall cardiovascular health. The circulatory system comprises the cardiovascular system (heart and blood vessels) and lymphatic system, working together to transport nutrients, oxygen, hormones, and waste products throughout the body. Detoxifying the lymphatic system can positively impact the circulatory system by reducing the burden on the heart, improving circulation, and promoting overall cardiovascular health. A healthier lymphatic system can help prevent conditions like edema (fluid retention), inflammation, and circulation issues, which can strain the heart and other organs over time. Therefore, the lymphatic system can have significant benefits for overall health, including improved blood flow and circulatory system function. By supporting the body's natural detoxification processes and promoting lymphatic health, individuals can enhance their immune response, reduce inflammation, and support optimal cardiovascular function [20].  In summary, while the blood circulatory system primarily transports oxygen and nutrients, and removes waste products, the lymphatic system complements this function by maintaining fluid balance, aiding in immune responses, and promoting overall health and well-being. These systems work in conjunction to support the body's functions and protect it from infections and disease.

Post-COVID

Post-COVID, some individuals may experience lingering effects on various body systems, including the cardiovascular system [21]. Blood flow can be affected in several ways following a COVID-19 infection such an increased risk of blood clot formation (hypercoagulability), which can lead to conditions like deep vein thrombosis, pulmonary embolism, and stroke. Even after recovering from the acute phase of the infection, some individuals may continue to have an increased risk of blood clots due to ongoing inflammation and changes in the coagulation system. The virus that causes COVID-19, SARS-CoV-2, can damage the endothelial cells lining blood vessels. Endothelial dysfunction can impair the ability of blood vessels to dilate and contract properly, affecting blood flow regulation. This dysfunction can persist post-infection, leading to issues with blood flow and potentially contributing to cardiovascular complications. COVID-19 can also impact the small blood vessels, leading to microvascular dysfunction. This can affect blood flow to various organs and tissues, potentially contributing to complications such as myocardial damage, kidney injury, and neurological issues. Some individuals with "long COVID" may experience symptoms like fatigue, chest pain, shortness of breath, and brain fog, which could be related to ongoing circulatory issues and impaired blood flow. These symptoms may persist even after the infection has cleared up. COVID-19 can directly affect the heart muscle, causing myocarditis (inflammation of the heart), arrhythmias, and heart failure. These cardiovascular complications can impact blood flow and cardiac function, leading to long-term consequences for overall circulation [22]. COVID-19 can also affect the autonomic nervous system, which controls functions like heart rate, blood pressure, and blood flow regulation. Dysregulation of the autonomic nervous system post-infection can impact cardiovascular function and blood flow dynamics. Individuals experiencing persistent symptoms related to blood flow post-COVID should seek medical evaluation and monitoring by healthcare professionals. Treatment may involve managing underlying cardiovascular risk factors, monitoring for complications such as blood clots, and implementing strategies to support cardiovascular and overall health. Regular follow-up with healthcare providers can help manage potential long-term effects on blood flow and cardiovascular function following a COVID-19 infection [23].

Vaccine Effects to Blood Flow

There have been concerns and reports about potential side effects related to blood clotting following some COVID-19 vaccinations [24]. These side effects, such as vaccine-induced immune thrombotic thrombocytopenia (VITT) or cerebral venous sinus thrombosis (CVST), have been associated with certain COVID-19 vaccines.  VITT is a serious condition characterized by blood clots combined with low platelet levels and can occur after vaccination with adenoviral vector-based vaccines. These blood clots typically involve unusual sites such as cerebral venous sinuses, abdominal veins, or other atypical locations. Pathogenesis is believed to involve an immune response that triggers platelet activation and clot formation, leading to thrombosis. CVST is a specific type of blood clotting disorder affecting the major veins that drain blood from the brain. There are Reports that have linked cases of CVST to COVID-19 vaccines [25-28].

Neuropathy

Peripheral neuropathy is a condition that affects the nerves outside the brain and spinal cord [29]. While not commonly reported, there have been cases where individuals experience peripheral neuropathy following a COVID-19 infection. According to Saif, et al., (2022) [30], post-COVID peripheral neuropathy can present with symptoms such as individuals experiencing abnormal sensations like numbness, tingling, or pins-and-needles in the hands, feet, or other areas of the body. Some individuals may experience a burning or shooting pain in the affected areas, which can be constant or intermittent. Weakness in the muscles controlled by the affected nerves is a common symptom of peripheral neuropathy. Peripheral neuropathy can affect proprioception, leading to difficulties with coordination and balance. Some individuals may experience increased sensitivity to touch or pain in the affected areas. The exact mechanisms by which COVID-19 may lead to peripheral neuropathy are not fully understood. However, several theories have been proposed, including direct viral damage to nerves, immune system-mediated nerve damage, inflammation-related nerve injury, or side effects of medications used in the treatment of COVID-19 [31,32].

Management of Post-COVID Peripheral Neuropathy

Management of post-COVID peripheral neuropathy may involve a multidisciplinary approach [33], including pain management medications such as gabapentin, pregabalin, or other neuropathic pain medications may be prescribed to help alleviate symptoms. Physical therapy exercises and techniques can help improve muscle strength, flexibility, and coordination, as well as manage pain and discomfort. Occupational therapy may be beneficial for individuals experiencing difficulty with daily activities due to peripheral neuropathy. Making lifestyle changes such as maintaining a healthy diet, managing underlying medical conditions like diabetes, and incorporating regular exercise can help manage symptoms and improve overall health. It is important for individuals with post-COVID peripheral neuropathy to have regular check-ups with healthcare providers to monitor their symptoms, progression, and response to treatment.

How Diet Affects Blood Flow

Diet plays a significant role in affecting blood flow and overall cardiovascular health [34,35]. There are several ways in which diet can impact blood flow such as consuming a diet high in sodium (table salt) can elevate blood pressure, leading to hypertension. High blood pressure can damage blood vessels over time, impairing blood flow and increasing the risk of cardiovascular diseases like heart attacks and strokes. Eating a diet rich in potassium, magnesium, and calcium, found in fruits, vegetables, whole grains, and dairy products, can help regulate blood pressure and support healthy blood flow. Saturated and Trans fats found in fried foods, fatty meats, and processed snacks can raise Low-Density Lipoprotein (LDL) cholesterol levels in the blood. High levels of LDL cholesterol can contribute to plaque buildup in arteries, narrowing blood vessels, and restricting blood flow. Including heart-healthy fats like monounsaturated and polyunsaturated fats from sources like olive oil, avocados, nuts, and seeds can help lower LDL cholesterol and maintain healthy blood flow. Certain foods high in sugar, refined carbohydrates, and unhealthy fats can promote inflammation in the body. Chronic inflammation can damage blood vessels and impair blood flow by increasing the risk of atherosclerosis and blood clot formation. Anti-inflammatory foods such as fruits, vegetables, whole grains, fatty fish, and some nuts can help reduce inflammation and support healthy blood flow. Diets high in sugary foods and refined carbohydrates can lead to spikes in blood sugar levels, causing inflammation and damage to blood vessels. Over time, uncontrolled blood sugar levels can contribute to conditions like diabetes and impaired blood flow. Choosing complex carbohydrates, fiber-rich foods, and sources of lean protein can help stabilize blood sugar levels and support optimal blood flow. Antioxidants found in colorful fruits and vegetables, as well as some nuts, seeds, and green tea, can help protect blood vessels from damage caused by free radicals. Antioxidant-rich foods can help maintain the elasticity of blood vessels and promote healthy blood flow. Adopting a balanced and nutritious diet that includes a variety of fruits, vegetables, whole grains, lean proteins, and healthy fats can positively influence blood flow and cardiovascular health.  It is important to limit intake of processed foods, sugary beverages, and foods high in unhealthy fats to support optimal blood flow and reduce the risk of cardiovascular diseases [36].

Diabetic Enhanced Peripheral Neuropathy and Blood Flow Effects

Peripheral neuropathy from diabetes is a common complica­tion that affects the nerves, particularly those in the extremities such as the feet and legs [37,38]. This condition is associated with nerve damage caused by prolonged high blood sugar levels. Periph­eral neuropathy can impair sensory and motor function and may also impact blood flow in several ways such as Nerve Damage and Blood Vessel Function where peripheral neuropathy can damage the nerves that control blood vessel function, leading to abnormal­ities in blood flow regulation. This can result in reduced blood flow to the extremities, including feet and legs. Diabetes-related periph­eral neuropathy can contribute to microvascular complications, including damage to the small blood vessels supplying the nerves. Impaired microcirculation can further exacerbate nerve damage and affect blood flow in the affected areas. Peripheral neuropathy in diabetes is often associated with other vascular complications such as peripheral arterial disease (PAD). PAD involves the narrowing or blockage of blood vessels in the extremities, reducing blood flow to the affected areas and causing symptoms like pain, cramping, and impaired wound healing. Nerve damage from peripheral neurop­athy can affect the nerves responsible for regulating blood flow in response to changes in temperature. This dysfunction may lead to difficulties in maintaining appropriate blood flow to control skin temperature, increasing the risk of skin breakdown and infections in diabetic individuals [33,39]. Peripheral neuropathy can also cause a loss of sensation in the feet and legs, making it difficult for individuals with diabetes to perceive injuries or wounds. Impaired blood flow due to neuropathy can further delay wound healing and increase the risk of developing ulcers or infections.

Managing diabetic enhanced peripheral neuropathy and its effects on blood flow involves a comprehensive approach that in­cludes controlling blood sugar levels, optimizing blood pressure and cholesterol levels, regular monitoring of foot health, and adopt­ing a healthy lifestyle. Individuals with diabetes and peripheral neuropathy should work closely with healthcare providers, includ­ing endocrinologists, neurologists, and podiatrists, to develop a personalized treatment plan to prevent complications and improve quality of life. Early detection, timely intervention, and diligent foot care practices are essential in managing diabetic neuropathy and preserving optimal blood flow to prevent further complications [39].

Protein Enzyme and Neuroplasticity

Neuroplasticity refers to the brain’s ability to reorganize itself by forming new neural connections throughout life. Neuroplasticity and blood flow can be enhanced through a combination of dietary supplements included in the products such as the Protein Enzyme Capsules which have been shown to stimulate better health and health maintenance [40,41] Activities like learning, practicing new skills, and experiencing new environments can promote neu­roplasticity. Key dietary supplements for improving circulatory health are the lumbrokinase which is a group of enzymes extracted from earthworms that may have potential benefits for cardiovas­cular health by helping to prevent blood clots; nattokinase is an­other enzyme, derived from the Japanese food natto, known for its potential to support cardiovascular health by promoting healthy blood flow and reducing blood clot formation; serrapeptase is an enzyme produced by the silkworm that may have anti-inflamma­tory properties and be used to support various health conditions, particularly related to inflammation and tissue repair; lipase is an enzyme that helps break down fats (lipids) in the digestive system, aiding in their absorption and utilization and may affect neuroplas­ticity; tudca is a compound that has been studied for its potential to support liver health and promote bile flow. It may also have anti­oxidant and anti-inflammatory properties; lymph cleanse is meth­ods or supplements aimed at supporting the lymphatic system, which plays a crucial role in immune function and detoxification by removing waste and toxins from the body; liver cleanse involves various protocols or supplements designed to support liver health and function, often involving dietary changes, herbal remedies, or specific detoxification programs; gallbladder cleanse include practices or supplements that aim to promote gallbladder health and function, often by supporting bile production and flow, which aids in digestion and detoxification; kidney cleanse helps to clean the kidney nephrons and reduce levels of creatinine. Blood flow and health encompasses various factors that influence circulatory health, including maintaining healthy blood pressure, cholesterol levels, blood viscosity, and overall cardiovascular fitness [24].

Capillary Leakage and Brain Neuropathy

Capillary leakiness refers to the increased permeability of tiny blood vessels called capillaries, allowing fluid, proteins, and cells to leak out into the surrounding tissues. When capillaries become leaky, it can have implications for brain injury and the healing process [42]. Capillary leakiness can impact brain injury and healing; following a brain injury, such as trauma, stroke, or neurodegenerative conditions, capillary leakiness can occur as part of the inflammatory response. Increased permeability of capillaries in the brain can lead to the leakage of blood constituents, immune cells, and fluid into the surrounding brain tissue. Capillary leakiness in the brain can exacerbate brain edema (swelling) and increase intracranial pressure, potentially causing further damage to brain cells and impairing neurological function. Capillary leakiness is often associated with inflammation, where inflammatory mediators contribute to the breakdown of the blood-brain barrier (BBB) and promote vascular permeability. The leakage of inflammatory cells and molecules into the brain can trigger a cascade of events that exacerbate tissue damage and hinder the healing process. In conditions involving brain injury, persistent capillary leakiness can impede the healing process by disrupting the normal microenvironment required for tissue repair and regeneration. Excessive leakage of fluid and proteins can lead to the formation of edema, impairing nutrient delivery and waste removal in the injured brain tissue. Capillary leakiness can also disrupt the Blood-Brain-Barrier (BBB), a specialized structure consisting of blood vessels, astrocytes, neurons, and other cells that regulate brain function and maintain brain homeostasis. Disruption of the BBB due to capillary leakiness can compromise cerebral blood flow, nutrient supply, and waste clearance, impeding the brain's ability to recover from injury.  Managing capillary leakage in the context of brain injury and healing may involve strategies to restore the integrity of the blood-brain-barrier, reduce inflammation, and promote vascular stability. Therapies aimed at controlling vascular permeability, such as anti-inflammatory medications, barrier-stabilizing agents, and neuroprotective interventions, may be beneficial in managing brain injuries associated with capillary leakiness. Understanding the role of capillary leakage in brain injury and healing is crucial for developing targeted interventions to mitigate its detrimental effects and support optimal recovery outcomes. Additionally, ongoing research in the field of neurovascular biology aims to identify novel treatment approaches that can effectively modulate vascular permeability and promote brain repair following injury [43].

Factors and Problem Areas Specific to Capillaries, Veins and Arteries

The problems associated with Capillaries include the weakness in the capillary walls that can result in increased fragility, leading to capillary leakage and the formation of small bruises or petechi­ae; an abnormal growth of blood vessels in the form of capillary hemangiomas can cause localized swellings or masses, potentially affecting nearby tissues [44], and the weakening of capillary walls due to conditions like hypertension or diabetes can result in the formation of small bulges or microaneurysms, particularly in the retina (Capillary Microaneurysms).

The challenges associated with the Veins include the weakening of vein walls and valves that can lead to the formation of varicose veins, visible as twisted, enlarged veins that often cause discomfort and cosmetic concerns; formation of blood clots within deep veins (Deep Vein Thrombosis (DVT)), typically in the legs, which can lead to pain, swelling, and potentially life-threatening complications if the clot dislodges and travels to the lungs (pulmonary embolism) [45], and failure of venous valves to prevent blood flow back to the heart can result in chronic venous insufficiency, characterized by swelling, skin changes, and the development of venous ulcers.

Arteries are affected by build-up of plaque (cholesterol, fats, and other substances) inside arterial walls, narrowing the arteries and impeding blood flow. Atherosclerosis is a major factor in coronary artery disease, peripheral arterial disease, and stroke; the weak­ness in the arterial wall can cause the vessel to bulge or balloon out, forming an aneurysm that may rupture and lead to life-threatening bleeding [46]; and the inflammation of the arteries, such as in giant cell arteritis or Takayasu arteritis, can cause vessel narrowing, re­duced blood flow, and potentially ischemic complications in various organs [47].

Understanding these potential problems in capillaries, veins, and arteries is crucial for early detection, diagnosis, and appro­priate management of vascular pathologies. Timely intervention, lifestyle modifications, medication, and in some cases, surgical procedures may be necessary to treat these conditions and prevent complications that can impact overall health and well-being. Reg­ular monitoring and preventive measures can help maintain vas­cular health and reduce the risk of developing associated vascular diseases.

Pathogens and Blood Flow

Pathogens, such as bacteria, viruses, and parasites, can have significant effects on blood flow in the body. When the body is invaded by pathogens, the immune system responds by triggering a series of events that can lead to changes in blood flow. Pathogens trigger the immune system to release inflammatory mediators in response to infection. Inflammation can cause blood vessels to dilate and become more permeable, leading to increased blood flow to the affected area as white blood cells and other immune cells are recruited to fight off the pathogen. Some pathogens can directly or indirectly induce a hypercoagulable state, leading to the formation of blood clots within blood vessels (thrombosis). Blood clots can disrupt normal blood flow, potentially causing blockages that can lead to tissue damage or even organ failure. Pathogens like certain bacteria and viruses can directly damage blood vessels, leading to impaired blood flow. This damage can compromise the structural integrity of blood vessels, affecting their ability to regulate blood flow and increasing the risk of complications such as hemorrhage or reduced blood supply to tissues.  Severe infections, particularly from bacterial pathogens, can trigger a systemic inflammatory response known as sepsis. In septic shock, blood flow to vital organs may be compromised due to widespread vasodilation, reduced vascular tone, and abnormal clotting, leading to multiorgan failure and poor tissue perfusion. Pathogens may also affect blood flow by modulating the immune response. Some pathogens can evade immune surveillance or manipulate immune cells to their advantage, impacting the inflammatory response and blood flow regulation in the infected tissues.

Overall, the effects of pathogens on blood flow changes are complex and can vary depending on the type of pathogen, the site of infection, and the host's immune response. Proper diagnosis, treatment, and management of infections are essential in preventing severe complications that may impact blood flow and overall health. Early recognition of signs and symptoms of infection and prompt medical intervention are crucial in addressing potential blood flow disturbances caused by pathogens [48].

Metabolic Actions, Blood Flow and Immunity

Immunity, vascular profusion, blood toxicity, and glucose metabolic actions play a vital role in overall health and well-being governed by blood flow. The immune system and blood flow are interconnected and play essential roles in maintaining overall health and responding to threats such as infections and diseases [49].

Blood flow is critical for the circulation of immune cells throughout the body. Immune cells, including white blood cells (leukocytes), travel through the bloodstream to reach sites of infection, inflammation, or tissue damage where they are needed to fight off pathogens, repair tissues, and support the immune response.  Proper blood flow ensures the delivery of essential nutrients and oxygen to immune cells, tissues, and organs involved in the immune response. Adequate nutrient and oxygen supply is necessary for immune cell function, proliferation, and the production of antibodies and cytokines needed to combat infections and maintain immune health. Blood flow also helps remove waste products generated during immune responses, such as dead pathogens, cellular debris, and metabolic by-products. Efficient removal of waste ensures the immune system can function optimally without being hindered by the accumulation of harmful substances [34].Blood flow is closely linked to inflammation, a critical component of the immune response. Inflammation is a protective mechanism that helps the body fight infections and repair tissues. Adequate blood flow is necessary to transport immune cells and signaling molecules to sites of inflammation and to support the resolution of inflammation once the threat is eliminated. Blood flow facilitates immune surveillance, the continuous monitoring of the body for potential threats like pathogens, cancer cells, and abnormal tissues. Immune cells circulate throughout the bloodstream and lymphatic system, patrolling for foreign invaders and recognizing and eliminating abnormal cells before they can cause harm. Proper blood flow is essential for the immune system to support tissue healing and repair processes. Immune cells, growth factors, and other factors delivered by blood flow play crucial roles in tissue regeneration, scar formation, and the restoration of normal function after injuries or infections. In autoimmune diseases, where the immune system mistakenly attacks healthy tissues, proper blood flow is needed to deliver immune cells and regulatory molecules to affected sites. Imbalances in blood flow and immune response can contribute to the development and progression of autoimmune conditions. Maintaining a healthy immune system and promoting optimal blood flow are important for overall health and resilience against infections, diseases, and other challenges. Strategies that support both immunity and blood flow include a balanced diet rich in nutrients, regular exercise, adequate hydration, stress management, sufficient sleep, and avoiding harmful habits like smoking and excessive alcohol consumption [50].

Immune support

There are products such as Immune Support TM that is primar­ily Grape Seed Powder and Pine Bark Extract in an herbal energized mixture that includes bentonite clay for mineral infusion and NAC. It helps additionally detox the blood using herbal combinations not found in other detox products. Previous studies have indicat­ed the benefit of Grape Seed Powder (Vitis vinifera) as it contains proanthocyanidins, a powerful antioxidants that protect against oxidative stress and may reduce the risk of chronic diseases, may improve circulation and lower cholesterol, supporting overall car­diovascular health, and its anti-inflammatory properties can help reduce swelling and pain in conditions like arthritis [51,52]. As documented by [51], Grape seed is an important natural bioactive product with various health benefits. Bioactive substances isolated from food ingredients may be used as natural alternative medicine for treating various diseases [53]. Grape seed, a major source of catechins and procyanidins, is readily available, inexpensive, and beneficial to human health [54]. Grape seed powder (GSP) has an­tioxidant, anti-inflammatory, antidiabetic, anti-obesity, anticancer, anti-aging, and antimicrobial properties [55,56]. Therefore, it has a potential role as a substitute or complement to drugs against dif­ferent diseases.

Resveratrol and Vitamins in Grape Seed Powder

Grape seeds are known to contain various beneficial compounds, including resveratrol and vitamins. Here is an overview of the key components found in grape seed powder, resveratrol, and the vitamins commonly present in grape seeds:

Grape Seed Powder (Vitis vinifera)

Grape seed powder also contains dietary fiber, which is import­ant for digestive health, promoting bowel regularity, and support­ing overall gut health. Grape seed powder may contain essential fatty acids like omega-3 and omega-6 fatty acids, which are ben­eficial for heart health and inflammation regulation. Resveratrol which is found in grape skins and seeds is a natural polyphenol that has antioxidant and anti-inflammatory properties [57]It is believed to offer various health benefits, including cardiovascular protec­tion, anti-aging effects, and potential anticancer properties. Res­veratrol has been studied for its potential to improve heart health by supporting healthy blood pressure, cholesterol levels, and blood vessel function. Resveratrol is also known for its anti-aging prop­erties, potentially supporting longevity and overall well-being by combating oxidative stress and inflammation. In terms of Vitamins; Grape seeds contain vitamin E, a fat-soluble antioxidant that helps protect cells from damage. Vitamin E is important for skin health, immune function, and overall antioxidant activity in the body. While grape seeds themselves may not be a significant source of vitamin C, the fruit itself is rich in this vitamin, which plays a crucial role in immune function, collagen production, and as an antioxidant pro­tecting against free radical damage. Grape seeds may also contain small amounts of vitamin K, which is essential for proper blood clotting, bone health, and cardiovascular health.

Incorporating grape seed powder, resveratrol, and grape-de­rived vitamins into a diet may offer potential health benefits, par­ticularly in terms of antioxidant protection, cardiovascular support, and overall well-being. It is important to consume these compo­nents as part of a balanced and varied diet to harness their full range of health-promoting properties. Grapes are one of the most consumed fruits worldwide. Grape seeds are rich in vitamins, fiber, and polyphenols, which are functional ingredients that can address various health issues by boosting natural physiological processes [53]. Grape seed can be collected as a byproduct from any wine manufacturing industry and the seeds of red wine grapes are usual­ly used in the preparation of GSP [53]. GSP attenuates the intracel­lular formation of Reactive Oxygen Species (ROS) and is considered a natural antioxidant and free radical scavenger [55]. GSP (Grape Seed Powder) improves inflammation and hyperglycemia associat­ed with obesity [58]. In addition, it prevents inflammation by mod­ulating the expression of cytokines, such as C-reactive protein, IL-6, and TNF-alpha [59]. In addition, GSP prevents tumorigenesis and show chemo-preventive properties against various cancers [60]. It may also be effective against the development of Alzheimer’s dis­ease and potentially other neurodegenerative disorders [56]. GSP can also modulate the GI tract; it suppresses DSS-induced colitis in the intestine through the improvement of the intestinal barrier, reduction of oxidative stress, and modulation of inflammatory cyto­kines and gut microbiota, suggesting its potential applicability as an adjuvant therapy for ulcerative colitis [52]. GSP has protective roles against inflammatory bowel disease through its ability to influence gut inflammation, the expression of tight junction proteins, and gut microbiota [56]. [52]pointed out that the Grape Seed Extract (GSE) is a complex polyphenolics mixture containing flavonoïds, non-fla­vonoïds, proanthocyanidins exhibiting multi-organ protection in various experimental settings [61]. For instance, GSE protects the heart [62], the liver [63], the brain [64] and the kidney [65] against high fat diet (HFD)-induced obesity. Furthermore high dosage GSE was even shown to improve renal injury in type 2 diabetic through its anti-oxidant and anti-inflammatory properties [65], and also to protect against arsenic [66], cisplatin [67], amikacin [68], and cyc­losporine A-induced nephrotoxicity [69].

N-Acetylcysteine (NAC)

The properties of N-Acetylcysteine (NAC) include enhancing glutathione S-transferase activity, repleting glutathione, scavenging free radicals, and stabilizing protein structures by crosslinking cysteine disulfide molecules along with its antioxidant, anti-inflammatory, and mucolytic properties [70]. NAC has been used clinically in cystic fibrosis since 1969[71]. NAC use has been expanded to acetaminophen overdose and chronic obstructive lung disease and its role is ever expanding clinically.

As reported by [72], NAC is the antidote for acetaminophen toxicity and has been used as a beneficial drug treatment for liver disorders. Its use and benefits have been reported in multiple other conditions and is attributed to the fact that it increases levels of glutathione, the body’s major antioxidant [63]. NAC is a potential treatment option for both acute and chronic diseases characterized by the generation of free oxygen radicals [73]. NAC has antioxidant properties, which has been attributed to its role as a precursor of glutathione [74]. Oxidative stress is one of the pathogenetic mechanisms causing liver damage. It contributes to initiation and progression of steatosis, fibrosis, and hepatic dysfunction in a variety of liver disorders [75,76]. NAC stimulates glutathione biosynthesis by providing cysteine, which is involved in a rate-limiting step in glutathione synthesis. Glutathione is essential for the body’s antioxidant defenses (Dodd et al., 2008). In addition to oxidative stress, nitrosative stress mechanisms are involved in the pathogenesis of chronic liver diseases. In the presence of reactive oxygen species, nitric oxide forms peroxynitrites which have deleterious effects [76]. Nitric oxide contributes to liver ischemia-reperfusion injury. Inhibition of Inducible Nitric Oxide Synthase (INOS) shows beneficial effects and NAC modulates expression of iNOS in human hepatocytes stimulated by proinflammatory cytokines [76]. This may be the basis of beneficial effects of NAC in chronic liver diseases [76]. NAC has been used successfully for chronic liver disorders such as chronic hepatitis C [77,78].

Brown Rice

Brown rice is a whole grain that retains its bran and germ, making it a good source of fiber, vitamins, and minerals such as manganese, selenium, and magnesium: The fiber in brown rice helps slow down the absorption of sugar, assisting in blood sugar regulation, which can be beneficial for those managing diabetes or at risk of developing it. Brown rice's fiber content can also help lower cholesterol levels, potentially reducing the risk of heart disease. The fiber in brown rice supports healthy bowel movements and contributes to overall digestive health [79,80].

Calcium

Calcium is essential for the development and maintenance of strong bones and teeth. It is also necessary for muscle contraction, including the beating of the heart [81,82].

Chromium

Chromium helps maintain normal blood sugar levels by enhancing the action of insulin and contributes to the metabolism of carbohydrates, fats, and proteins [83,84].

Iodine

Iodine is crucial for the production of thyroid hormones, which regulate metabolism, growth, and development. It is important for brain development, especially during pregnancy and infancy [85,86].

Magnesium

Magnesium is essential for bone formation; magnesium contributes to the structural development of bone and is vital for the absorption and metabolism of calcium. It also plays a crucial role in muscle contractions, helping to prevent cramps by allowing muscles to relax. It's particularly beneficial for athletes or those with frequent muscle soreness. Magnesium is important for the proper functioning of the nervous system. It helps regulate neurotransmitter activities that send messages throughout the brain and nervous system, aiding in the reduction of stress and anxiety. It further supports heart health by maintaining a normal heart rhythm, helping to regulate blood pressure, and is linked to a lower risk of cardiovascular disease. Magnesium plays a role in glucose control and insulin metabolism. A magnesium-rich diet is associated with a lower risk of type 2 diabetes. Some studies suggest that magnesium deficiency may be linked to migraines. Supplementing with magnesium can reduce the frequency and severity of migraines for some individuals. Magnesium can improve sleep quality, especially for those with insomnia, by helping to relax the body and mind. It regulates melatonin, which guides sleep-wake cycles in the body [87,88].

Manganese

Manganese contributes to the formation of bone and is important for bone health and development. It also helps form an antioxidant enzyme that protects cells from damage [89,90].

Miracle Clay (Bentonite Clay)

Miracle Clay adsorbs and removes toxins, heavy metals, and impurities from the body, promoting detoxification. When used topically, it can help in treating skin conditions like acne by absorbing excess oil and reducing inflammation. It may support digestive health by absorbing toxins in the gut and providing relief from issues like bloating and constipation [91,92].

Molybdenum

Molybdenum is vital for the function of certain enzymes involved in detoxification and the metabolism of sulfur-containing amino acids [93,94].

Reishi Mushrooms (Ganoderma lucidum)

Reishi Mushrooms is known to enhance immune function through its effects on white blood cells, particularly in people who are ill, such as those with cancer. It is often used to reduce stress and promote sleep and relaxation [95,96].

Zinc

Zinc is crucial for the development and function of immune cells. It also plays a role in collagen synthesis and is important for skin health and wound healing [97,98].

Vascular Occlusion

Occlusion of blood flow in veins, capillaries, and arteries can have specific effects on health due to their unique roles in the circu­latory system. Vein occlusion, particularly in deep veins of the legs or arms, can lead to the formation of blood clots known as Deep Vein Thrombosis (DVT). If a clot dislodges and travels to the lungs, it can cause a life-threatening condition called pulmonary embo­lism. Vein occlusion or damage can lead to Chronic Venous Insuffi­ciency (CVI), a condition in which veins struggle to return blood to the heart efficiently. CVI symptoms include swelling, leg pain, skin changes, and ulcers. Untreated CVI can impact quality of life and lead to complications. Vein occlusion can contribute to the develop­ment of varicose veins, which are enlarged, twisted veins that often appear in the legs. Varicose veins may cause discomfort, swelling, and cosmetic concerns. Capillaries are crucial for the exchange of oxygen, nutrients, and waste products between blood and tissues. Occlusion of capillaries can lead to tissue ischemia, where tissues receive inadequate blood supply. This can result in tissue damage, dysfunction, and impaired healing. In conditions like diabetes, cap­illary occlusion can contribute to microvascular complications, in­cluding diabetic retinopathy (eye disease), nephropathy (kidney disease), and neuropathy (nerve damage). These complications can impact vision, kidney function, and neurological health. Ath­erosclerosis (aka Arterial occlusion) is a condition characterized by the buildup of plaque in the arteries. Atherosclerosis can lead to ar­terial stenosis or blockages, reducing blood flow to vital organs and tissues. Arterial occlusion in the peripheral arteries, typically in the legs, can cause PAD. Symptoms of Peripheral Artery Disease (PAD) include leg pain, cramping, numbness, and slow wound healing. Severe cases of PAD can lead to tissue damage and risk of limb am­putation. Arterial occlusion in the coronary arteries supplying the heart can lead to Coronary Artery Disease (CAD), a major cause of heart attacks and other cardiovascular events. Reduced blood flow to the heart muscle can result in chest pain (angina), arrhythmias, and myocardial infarction. Management of occluded blood flow in these different types of blood vessels may involve lifestyle modifi­cations, medications (such as anticoagulants or antiplatelet drugs), interventions (like angioplasty, stenting, or bypass surgery), and disease-specific treatments to address underlying conditions con­tributing to vascular occlusion. Early detection, prompt treatment, and ongoing management are essential to minimize complications and maintain overall health and well-being [99].

All Clear Herbal combination for improving blood flow

Product such as the All-Clear TM is a herbal combination for improving blood flow. This product is a combination of various en­zymes primarily from horseradish, wasabi and other plant extracts. These enzymes help mitigate oxidative stress to a considerable extent by destroying cellular hydrogen peroxide to produce water and oxygen and may affect pathogenesis of many age-associated degenerative diseases. Wasabia japonica has anti-inflammatory, anti-microbial, and has been found to inhibit platelet aggregation, a property useful in the elderly, where preventing excessive clot­ting is vital. Horseradish has been used for a long time in tradition­al medicine; consumption can normalize the arterial pressure and prevent the risk of blood clots formation, and can enhance the elas­ticity of cerebral and coronary blood vessels, thus reducing the risk of an infarct or cerebrovascular accident. A recently published case study clearly demonstrates the action of ALL-CLEAR in dissolving arterial blood clots and allowing normal blood flow to be achieved in as little as 7-days of use [29,99]. Previous studies have demon­strated the importance of the ingredients found in the All Clear^TM as follows.

BrownRice

Brown rice is a whole grain that retains its bran and germ, mak­ing it a good source of fiber, vitamins, and minerals such as manga­nese, selenium, and magnesium.: The fiber in brown rice helps slow down the absorption of sugar, assisting in blood sugar regulation, which can be beneficial for those managing diabetes or at risk of developing it. Brown rice’s fiber content can also help lower choles­terol levels, potentially reducing the risk of heart disease. The fiber in brown rice supports healthy bowel movements and contributes to overall digestive health [69,70].

Catalase

Catalase is an enzyme found in nearly all living organisms. It serves to protect cells from oxidative damage by catalyzing the de­ composition of hydrogen peroxide, a potentially harmful by-prod­uct of many cellular processes, into water and oxygen. By reduc­ing oxidative stress, catalase may play a role in the aging process, potentially slowing down cellular aging and promoting longevity. Some theories suggest that catalase’s ability to break down hydro­gen peroxide might also relate to preventing or reducing the gray­ing of hair, as hydrogen peroxide can bleach hair from the inside out [100,101].

Horseradish (Armoracia rusticana)

Horseradish has been traditionally used to clear the sinuses and provide relief from respiratory conditions due to its strong pungent compounds that help thin and clear mucus. Contains compounds such as glucosinolates, which can have antimicrobial properties, potentially fighting off various pathogens and supporting immune health. May stimulate digestion by encouraging the production of digestive enzymes, thus improving gut health and nutrient absorp­tion [102,103].

Wasabi (Wasabia japonica)

Like horseradish, wasabi contains isothiocyanates, which are known for their anti-inflammatory effects and potential can­cer-preventing properties. The strong antimicrobial properties of wasabi may help reduce the risk of foodborne illnesses by inhibit­ing the growth of bacteria and fungi in food. Its pungent quality can also help clear sinuses and improve respiratory health, similar to horseradish [104,105].  

Detoxing

The concept of "detoxing" the blood is often promoted in various health and wellness circles as a way to cleanse the body of toxins and promote overall health. While the body naturally detoxifies itself through the liver, kidneys, skin, and other organs, some proponents suggest specific practices or products to support this process. Blood plays a critical role in transporting nutrients, oxygen, hormones, and waste products throughout the body. Toxins from environmental pollutants, processed foods, medications, and other sources can accumulate in the bloodstream over time. Supporting the body's natural detoxification processes can help remove these toxins and prevent their harmful effects on health. Toxins and impurities in the blood can compromise immune function and increase susceptibility to infections, inflammation, and chronic diseases. By maintaining clean and healthy blood, the immune system can function optimally and better defend the body against pathogens and disease. Detoxifying the blood can help improve circulation by reducing the buildup of plaque, cholesterol, and other substances that may hinder blood flow. Enhanced circulation ensures that oxygen and nutrients reach all parts of the body efficiently, promoting cellular function and overall vitality [106].

Detoxification Sites

The body has its own intricate and efficient mechanisms to detoxify and eliminate toxins naturally. Several organs and systems work together to perform this crucial function:

I. Liver plays a central role in detoxification- It processes and metabolizes toxins to make them less harmful or easier for the body to eliminate. The liver converts toxins into water-soluble compounds that can be excreted through urine or bile;

II. Kidneys- filter the blood and remove waste products and toxins, which are then excreted in the form of urine;

III. Lungs- Through respiration, the lungs help eliminate volatile substances and toxins from the body;

IV. Skin - Sweat glands in the skin help remove toxins from the body through perspiration;

V. Intestines- play a role in eliminating waste and toxins through bowel movements; and

VI. Lymphatic system- This system helps remove toxins and waste from cells and tissues and transport them to the blood to be filtered and eliminated [106].

Nutritional Detoxing

Antioxidants found in fruits, vegetables, and other foods help neutralize free radicals and reduce oxidative stress caused by tox­ins.

Drinking an adequate amount of water supports the body’s de­toxification process by helping flush out toxins through urine and sweat. Consuming a balanced diet rich in nutrients, getting reg­ular exercise, and reducing exposure to harmful substances like tobacco and excessive alcohol can support overall body detoxifi­cation. Living a healthy lifestyle that supports the body’s natural detoxification processes is the best approach to maintaining overall health and well-being. Certain toxins in the bloodstream can dis­rupt hormonal balance, leading to issues such as weight gain, mood swings, fatigue, and reproductive problems. Detoxifying the blood may help restore hormonal equilibrium and support optimal endo­crine function. The condition of the blood can significantly impact skin health. Detoxification of the blood may help reduce skin issues like acne, eczema, and premature aging by promoting the elimina­tion of toxins and enhancing nutrient delivery to the skin cells. A buildup of toxins in the blood can contribute to feelings of fatigue, sluggishness, and low energy levels. By detoxifying the blood, indi­viduals may experience increased energy, mental clarity, and over­all vitality. Detoxifying the blood can benefit the liver, kidneys, and other organs involved in the elimination of waste and toxins. By re­ducing the toxic burden on these organs, blood detoxification sup­ports their optimal functioning and longevity. It’s important to note that while supporting the body’s natural detoxification processes through healthy lifestyle practices like a balanced diet, hydration, regular exercise, adequate sleep, and stress management can be beneficial, extreme detox diets or regimens may not be necessary or safe for everyone [106].

Herbal Detox

This is another product whose ingredients based on previous studies have been shown to be a free-radical damage eliminator, particularly helping heart issues, diabetes and cancer. This product aids by detoxing the blood and organs using a free radical exchange mechanism. Helps improve circulation, reduce swelling, and may improve eye function. Has been shown to lower blood pressure and reduce cholesterol. The main ingredients are Brown Rice, Dandelion, Grape Seed Powder, NAC, Spirulina, Turmeric, and other herbal trace ingredients whose benefits based on previous studies are articulated as follows:

Brown Rice

Brown rice is a whole grain that retains its bran and germ, making it a good source of fiber, vitamins, and minerals such as manganese, selenium, and magnesium. The fiber in brown rice helps slow down the absorption of sugar, assisting in blood sugar regulation, which can be beneficial for those managing diabetes or at risk of developing it. Brown rice's fiber content can also help lower cholesterol levels, potentially reducing the risk of heart disease. The fiber in brown rice supports healthy bowel movements and contributes to overall digestive health [79,80].

Dandelion Root (Taraxacum officinale L.)

Dandelion Root is traditionally used to support liver function by helping with bile production and detoxification. It can act as a mild laxative and promote digestion by balancing the natural and beneficial bacteria in the intestines. Contains potent antioxidants that fight inflammation and may protect against cellular damage and disease [107,108].

Grape Seed Powder (Vitis Vinifera)

Grape Seed Powder contains proanthocyanidins, powerful antioxidants that protect against oxidative stress and may reduce the risk of chronic diseases, may improve circulation and lower cholesterol, supporting overall cardiovascular health, and its anti-inflammatory properties can help reduce swelling and pain in conditions like arthritis [51,52].

N-Acetylcysteine (NAC)

N-Acetylcysteine acts as a precursor to glutathione, one of the body's most important antioxidants, helping to reduce oxidative stress and cellular damage. Helps thin and loosen mucus in the airways, making it particularly beneficial for conditions such as chronic bronchitis. Supports liver health and detoxification, especially in cases of acetaminophen (Tylenol) overdose, by replenishing glutathione levels [72,70].

Spirulina

Spirulina is a type of blue-green algae that is incredibly high in nutrients, including protein, B vitamins, copper, and iron, making it a powerful dietary supplement. Contains phycocyanin, a pigment with potent antioxidant and anti-inflammatory properties. May have beneficial effects on cholesterol levels, blood pressure, and blood sugar control, contributing to cardiovascular health [109,110].

Turmeric (Curcuma longa),

The active compound in turmeric, curcumin, has powerful anti-inflammatory effects and is a strong antioxidant. May boost Brain-Derived Neurotrophic Factor (BDNF), linked to improved brain function and a lower risk of brain diseases. Can improve several factors known to play a role in heart disease, and its antioxidant and anti-inflammatory properties are believed to be beneficial for heart health [111,112].

Glucose Control and Blood Flow

Glucose control and blood flow are intricately connected pro­cesses that influence overall health, particularly in the context of conditions like diabetes and cardiovascular disease [113]. Diabetes can lead to poor circulation in several ways. The most common cul­prit is high blood glucose levels, which damage the lining of blood vessels and impede blood flow. Diabetes also increases the risk of peripheral arterial disease (PAD), an abnormal narrowing of the arteries principally in your legs and feet [114]. High blood glucose levels over time can lead to damage to blood vessels through a pro­cess called glycation. When blood sugar levels are consistently el­evated, excess glucose can attach to proteins in the blood vessels, forming harmful molecules called advanced glycation end products (AGEs). These AGEs can accumulate and cause damage to blood vessels in several ways [115,116]. Elevated glucose levels can im­pair the function of endothelial cells that line the blood vessels. This dysfunction can lead to reduced nitric oxide production, which is essential for blood vessel relaxation and proper blood flow regula­tion. High blood glucose levels can enhance oxidative stress in the body, leading to the production of free radicals that can damage blood vessel walls and impair blood flow. Chronic high blood glu­cose levels can trigger an inflammatory response in the blood ves­sels, contributing to damage and dysfunction. Prolonged exposure to high glucose levels can promote the formation of atherosclerotic plaques in the blood vessels, narrowing the vessels and restricting blood flow. These plaques can lead to conditions like atheroscle­rosis, increasing the risk of cardiovascular diseases. Small blood vessels, such as those in the eyes, kidneys, and nerves, are partic­ularly susceptible to damage from high blood glucose levels. This damage can lead to complications like diabetic retinopathy, ne­phropathy, and neuropathy. To mitigate the damage caused by high blood glucose to blood vessels and flow impedance, it is crucial for individuals with diabetes or elevated blood sugar levels to Maintain good glycemic control through medication, dietary changes, exer­cise, and regular blood sugar monitoring; Adopt a healthy lifestyle, including a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats; Engage in regular physical activity to improve blood circulation and reduce the risk of cardiovascular complications; Monitor and manage other cardiovascular risk fac­tors like hypertension, high cholesterol, and smoking; and Consult healthcare providers regularly to monitor blood sugar levels, assess cardiovascular health, and receive appropriate guidance and treat­ment. Managing blood glucose levels effectively can help prevent or reduce the damage to blood vessels and maintain proper blood flow throughout the body [117].

Glucose control affects blood flow and it is crucial for main­taining optimal health as persistently high blood glucose levels can damage the small blood vessels known as capillaries. This damage, termed microvascular complications, can impair blood flow to tis­sues and organs, leading to complications such as diabetic retinop­ athy, nephropathy, and neuropathy [118]. Elevated blood glucose levels are associated with an increased risk of atherosclerosis, a condition characterized by the buildup of plaque in the arteries. Atherosclerosis can restrict blood flow and predispose individuals to conditions like coronary artery disease, peripheral artery dis­ease, and stroke. Proper blood flow is crucial for the delivery of insulin to tissues, where it facilitates the uptake of glucose from the bloodstream. Impaired blood flow, as seen in conditions like ath­erosclerosis, can reduce insulin sensitivity and contribute to insulin resistance, a hallmark of type 2 diabetes. Adequate blood flow is essential for the transport of nutrients, oxygen, and immune cells to wounds for proper healing. In individuals with diabetes and poor glucose control, impaired blood flow can hinder the healing process and increase the risk of chronic wounds and infections. The endo­thelium, a layer of cells lining blood vessels, plays a critical role in regulating blood flow and vascular tone. High levels of glucose in the blood can lead to endothelial dysfunction, causing blood vessels to constrict and reducing blood flow to tissues.

Maintaining optimal blood glucose levels through diet, exercise, medication, and lifestyle modifications is essential for preventing microvascular and macrovascular complications associated with diabetes and impaired blood flow. Stable blood glucose levels sup­port proper blood circulation, ensuring that vital organs and tissues receive an adequate supply of oxygen and nutrients. This promotes overall health and function of the cardiovascular system. Chronic hyperglycemia can trigger inflammatory responses that contribute to endothelial dysfunction and atherosclerosis. By controlling blood glucose levels, individuals can reduce inflammation and improve vascular health, supporting optimal blood flow. In conclusion, con­trolling blood glucose l By adopting a holistic approach to managing glucose levels, individuals can optimize vascular health, reduce the risk of circulatory issues, and promote overall well-being. Regular monitoring of blood glucose levels, adherence to treatment plans, and lifestyle modifications are key components of effective glucose control and blood flow management [119].

Sugar Balance

There is another dietary supplement product called the Sugar Balance that is an entirely herbal product that is taken with meals based on traditional medicine from plants and minerals that allow the body to better balance the equation of blood glucose and insulin. The 3 capsule dose can last up to 18 hours, and studies have shown that the active ingredients help in the lowering of the blood glucose level that is a balance in harmony with the body’s normal digestive process maintaining an average variation rather than going to hy­poglycemic (low sugar) or hyperglycemic (high sugar) ends. When used regularly we have been told that it seems to restore the func­tionality of the pancreas and can lessen diabetes blood flow effects. Ingredients include Alpha Lipoic Acid, Brown Rice, Plant Extracts, Root Extracts, Seed Extracts, and other herbal trace ingredients where previous studies have shown the benefits.

Alpha Lipoic Acid, functions as a powerful antioxidant that can regenerate other antioxidants, helping to protect cells from oxi­dative damage which may improve insulin sensitivity and reduce blood sugar levels in people with type 2 diabetes. It offers protec­tive benefits against nerve damage, potentially beneficial for condi­tions like peripheral neuropathy [120,121].

Amla Stem Extract (Emblica Officinalis) is a potent source of vitamin C, supporting immune function and skin health through its antioxidant properties. It has been shown to help regulate blood sugar levels, making it beneficial for diabetes management. It may help improve cholesterol levels, supporting cardiovascular health [122,123].

Astragalus Root Extract (Astragalus Membranaceus) is known to strengthen the immune system and reduce inflammation. It of­fers cardiovascular protection by lowering blood pressure and im­proving heart function. It contains antioxidants that may help pro­tect against aging and promote longevity [124,125].

Bitter Melon Extract (Momordica charantia) contains com­pounds that can act like insulin, helping to lower blood sugar levels. It may help reduce high cholesterol levels, thereby supporting heart health [126,127].

Chromium helps maintain normal blood sugar levels by en­hancing the action of insulin and contributes to the metabolism of carbohydrates, fats, and proteins [126,127].

Cinnamon (Cinnamomum verum) has been shown to lower blood sugar levels and improve insulin sensitivity. It is high in pow­erful antioxidants that protect against oxidative damage. It contains anti-inflammatory properties that may help lower the risk of dis­ease [128,129].

Fenugreek Seed Extract (Trigonella Foenum-Graecum) can im­prove glucose tolerance and lower blood sugar levels due to its high fiber content. It may help reduce cholesterol levels, particularly LDL cholesterol. It has been used to suppress appetite and support weight loss efforts [130,131].

Gingko Biloba (Ginkgo biloba L) promotes good blood circu­lation and heart health by dilating blood vessels and reducing the stickiness of blood platelets. It is thought to improve cognitive func­tion, particularly in people with dementia or Alzheimer’s disease, by protecting against neuron damage [132,133].

Glucuronolactone is believed to aid in the detoxification pro­cesses of the liver. It is often included in energy drinks for its sup­posed energizing effects, although scientific support is limited [134,135].

Gymnema Leaf (Gymnema Sylvestre) may help reduce sugar absorption in the intestines and support the reduction of sugar cravings. It has been used traditionally to help with diabetes man­agement by supporting insulin production [136,137].

Inositol plays a role in neurotransmitter signaling, support­ing mental health and emotional well-being. It has been shown to improve the symptoms of polycystic ovary syndrome (PCOS) and enhance fertility in women. It may help improve insulin sensitivity and reduce blood sugar levels [138,139].

Java Plum (Syzygium Cumini) the fruit and seed extracts have been used to lower blood sugar levels in traditional medicine. It is rich in antioxidants, it may help protect against oxidative stress and reduce inflammation [140,141].

Magnesium Malate combines magnesium and malic acid, which can help improve energy production within cells. It may be partic­ularly beneficial for fibromyalgia and muscle pain due to its role in the Krebs cycle. The malate form is gentler on the stomach and may help manage symptoms of acid reflux [142,143].

Malabar Plum Seed Extract (Syzygium Jambos) may have prop­erties that help regulate blood sugar levels, though research is limited. It could provide antioxidants that help protect cells from damage [144,145].

Neem Leaf Extract (Azadirachta Indica) has been traditionally used for its detoxifying and purifying properties. It can be applied topically for antibacterial and anti-inflammatory benefits, often used in acne treatments. Neem is known for promoting oral hy­giene and reducing dental plaque [146,147].

Okra Leaf Powder (Abelmoschus Esculentus) has been asso­ciated with beneficial effects on blood sugar regulation due to its fiber content. The fiber in okra can help improve digestion and pro­mote a healthy gut [148,149].

Papaya Leaf Powder (Carica Papaya) contains enzymes like papain and chymopapain that aid in digestion and can help break down proteins, potentially easing digestive ailments. It is high in vitamins, minerals, and enzymes. Papaya leaf powder can boost the immune system and has anti-inflammatory properties. Some stud­ies suggest that papaya leaf extract can help in increasing blood platelet levels, beneficial especially in conditions like dengue fever [150,151].

Strawberry Tree Leaves (Arbutus unedo L) is rich in antioxi­dants, these leaves can help protect against oxidative stress and may reduce the risk of chronic diseases. The leaves have been used traditionally to reduce inflammation and as a diuretic to support urinary tract health. It contains compounds that exhibit antimicro­bial properties, potentially fighting off various pathogens [152,153].

Taurine may improve heart health by reducing blood pressure and calming the nervous system. Plays a crucial role in maintain­ing proper concentration and movement of electrolytes across cell membranes. Can enhance exercise performance by reducing fatigue, increasing fat burning, and decreasing muscle damage [154,155].

Turmeric (Curcuma longa), the active compound in turmeric, curcumin, has powerful anti-inflammatory effects and is a strong antioxidant. It may boost brain-derived neurotrophic factor (BDNF), linked to improved brain function and a lower risk of brain diseases. It can improve several factors known to play a role in heart disease, and its antioxidant and anti-inflammatory properties are believed to be beneficial for heart health [111,112].

Vitamin B12 (Cyanocobalamin) is essential for maintaining the health of nerve cells and supporting the production of nerve sheathing. Critical for producing red blood cells, which prevent ane­mia. Plays a role in converting carbohydrates into glucose, leading to energy production and reducing fatigue [156,157].

Vitamin B3 (Niacin) can significantly lower levels of bad LDL cholesterol and increase good HDL cholesterol. It is involved in the metabolism of carbohydrates, fats, and proteins into energy. It is essential for the health of the skin and nerves; also has a role in improving digestive function [158-160].

Vitamin B5 (Pantothenic Acid) is vital for the creation of coen­zyme A, necessary for various metabolic pathways, including ener­gy metabolism. It is crucial for synthesizing and metabolizing pro­teins, carbohydrates, and fats. It may enhance the healing process of skin wounds and contribute to skin health [161,162].

Conclusion

The concepts of blood flow, pathophysiology, the immune system, and nutrition are interconnected and play crucial roles in maintaining overall health and responding to disease. The connection is shown through; Pathophysiology- This involves the study of functional changes that occur in cells, tissues, and organs as a result of disease or injury. Disruption in normal physiological processes can lead to pathophysiological changes that contribute to the development and progression of various health conditions. For example, inflammation, oxidative stress, metabolic abnormalities, and cellular dysfunction are common pathophysiological mechanisms underlying many diseases.

Proper blood flow is essential for delivering oxygen, nutrients, hormones, and immune cells to tissues throughout the body. Disruption in blood flow can impair tissue function and lead to conditions such as ischemia, tissue damage, and organ dysfunction. pathophysiological conditions like atherosclerosis, hypertension, and blood clot formation can restrict blood flow, leading to serious health consequences. The immune system which is modulated by blood circulation plays a critical role in protecting the body against pathogens, infections, and foreign invaders. It consists of various cells, tissues, and molecules that work together to identify and eliminate harmful substances and invaders. Dysfunction in the immune system can result in autoimmune diseases, allergies, infections, and an impaired ability to fight off illnesses.

Nutrition provides the essential nutrients that support cellular function, energy production, and immune system activities. A balanced diet rich in vitamins, minerals, protein, carbohydrates, and fats is important for maintaining optimal health and circulation. Poor nutrition can weaken the immune system, impair wound healing, and increase susceptibility to infections and chronic diseases.

The relationships between nutrition, blood flow, and immunity are intricate and multidirectional. For instance, proper nutrition supports immune function by providing the necessary building blocks for immune cells and antibodies. The Infections and inflammatory processes can alter metabolic pathways, leading to deficiencies in cellular metabolism and energy production. Circulatory disturbances can impact immune responses by affecting the delivery of immune cells and functionaries to sites of infection or inflammation. Understanding how these interconnected systems interact and influence each other is essential for developing strategies to prevent, manage, and treat a wide range of health conditions. A holistic approach that considers the interplay between pathophysiology, blood flow, immune function, and nutrition is key to promoting optimal health and well-being.

Acknowledgment

Thanks to Harvey Klein, MD for providing valuable medical insights and reviewing the paper for accuracy.

Conflict of Interest

None.

References

• Caro CG, Parker KH, Doorly DJ (1995) Essentials of blood flow. Perfusion 10(3): 131-134.
• Bruning RS, Sturek M (2015) Benefits of exercise training on coronary blood flow in coronary artery disease patients. Prog Cardiovasc Dis 57(5): 443-453.
• Sharp PF (1994) The measurement of blood flow in humans using radioactive tracers. Physiol Meas 15(4): 339-379.
• Liu J, Min L, Liu R, Zhang X, Wu M, et al. (2023) The effect of exercise on cerebral blood flow and executive function among young adults: a double-blinded randomized controlled trial. Sci Rep 13(1): 8269.
• Pugsley MK, Tabrizchi R (2000) The vascular system. An overview of structure and function. J Pharmacol Toxicol Methods 44(2): 333-340.
• Tansey EA, Montgomery LEA, Quinn JG, Roe SM, Johnson CD (2019) Understanding basic vein physiology and venous blood pressure through simple physical assessments. Adv Physiol Educ 43(3): 423-429.
• Filosa JA, Morrison HW, Iddings JA, Du W, Kim KJ (2016) Beyond neurovascular coupling, role of astrocytes in the regulation of vascular tone. Neuroscience 323: 96-109.
• Papasilekas T, Themistoklis KM, Melanis K, Patrikelis P, Spartalis E, et al. (2021) A Brief Review of Brain's Blood Flow-Metabolism Coupling and Pressure Autoregulation. J Neurol Surg A Cent Eur Neurosurg 82(3): 257-261.
• Libby P (2021) Inflammation during the life cycle of the atherosclerotic plaque. Cardiovasc Res 117(13): 2525-2536.
• Augustin HG, Koh GY (2017) Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology. Science 357(6353): eaal2379.
• Agrawal P, Nikhade P, Patel A, Mankar N, Sedani S (2022) Bromelain: A Potent Phytomedicine. Cureus 14(8): e27876.
• Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, et al. (2015) A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212(7): 991-999.
• Hikisz P, Bernasinska-Slomczewska J (2021) Beneficial Properties of Bromelain. Nutrients 13(12): 4313.
• Hsu MC, Itkin M (2016) Lymphatic Anatomy. Tech Vasc Interv Radiol 19(4): 247-254.
• Kizhatil K, Ryan M, Marchant JK, Henrich S, John SW, et al. (2014) Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process. PLoS Biol 12(7): e1001912.
• Maghsoumi Norouzabad L, Alipoor B, Abed R, Eftekhar Sadat B, Mesgari Abbasi M, et al. (2016) Effects of Arctium lappa L. (Burdock) root tea on inflammatory status and oxidative stress in patients with knee osteoarthritis. International journal of rheumatic diseases 19(3): 255-261.
• Petrova TV, Koh GY (2020) Biological functions of lymphatic vessels. Science 369(6500) :eaax4063.
• Predes FS, Ruiz AL, Carvalho JE, (2011) Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts. BMC Complement Altern Med 25.
• Sharifi Rad M, Mnayer D, Morais Braga MFB, Carneiro JNP, Bezerra CF, et al. (2018) Echinacea plants as antioxidant and antibacterial agents: From traditional medicine to biotechnological applications. Phytotherapy research: PTR 32(9): 1653-1663.
• Xu W, Zhu H, Hu B, Cheng Y, Guo Y, et al. (2021) Echinacea in hepatopathy: A review of its phytochemistry, pharmacology, and safety. Phytomedicine : international journal of phytotherapy and phytopharmacology, 87: 153572.
• Lechner Scott J, Levy M, Hawkes C, Yeh A, Giovannoni G, et al. (2021) Long COVID or post COVID-19 syndrome. Mult Scler Relat Disord 55: 103268.
• Sonnenschein L, Weinberg R, Cotter HT, Salvo LA, Etyang T, et al. (2020) Historical and Current Conditions Including COVID-19 Requiring Anti-Pathogenic Surveillance and Proper Immunogenic Support: 8(4).
• Sonnenschein Leonard, Etyang Tiberious, Manga Selene, Wong Erna (2023) An Initial Evaluation of the Effectiveness of a Dietary Supplement Regimen on the Effects of Post-COVID Infection. Am J Biomed Sci & Res. 2023: 18(6).
• Yonker LM, Swank Z, Bartsch YC, Burns MD, Kane A, et al. (2023) Circulating Spike Protein Detected in Post-COVID-19 mRNA Vaccine Myocarditis. Circulation 147(11): 867-876.
• Sharifian Dorche M, Bahmanyar M, Sharifian Dorche A, Mohammadi P, Nomovi M, et al. (2021) Vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID-19 vaccination; a systematic review. J Neurol Sci 428: 117607.
• Medicherla CB, Pauley RA, de Havenon A, Yaghi S, Ishida K, et al. (2020) Cerebral Venous Sinus Thrombosis in the COVID-19 Pandemic. J Neuroophthalmol 40(4): 457-462.
• de Gregorio C, Colarusso L, Calcaterra G, Bassareo PP, Ieni A, et al. (2022) Cerebral Venous Sinus Thrombosis following COVID-19 Vaccination: Analysis of 552 Worldwide Cases. Vaccines (Basel) 10(2): 232.
• Ostovan VR, Foroughi R, Rostami M, Almasi Dooghaee M, Esmaili M, et al. (2021) Cerebral venous sinus thrombosis associated with COVID-19: a case series and literature review. J Neurol 268(10): 3549-3560.
• Barrell K, Smith AG (2019) Peripheral Neuropathy. Med Clin North Am 103(2): 383-397.
• Saif DS, Ibrahem RA, Eltabl MA (2022) Prevalence of peripheral neuropathy and myopathy in patients post-COVID-19 infection. Int J Rheum Dis 25(11): 1246-1253.
• Li Y, Chen Y, Sun Waterhouse D (2022) The potential of dandelion in the fight against gastrointestinal diseases: A review. Journal of ethnopharmacology 293: 115272.
• Yamamoto K (2022) Adverse effects of COVID-19 vaccines and measures to prevent them. Virol J 19(1): 100.
• Hanganu AR, Constantin A, Moise ES, Niculae CM, Olaru ID, et al. (2023) Peripheral nervous system involvement associated with COVID-19. A systematic review of literature. PLoS One 18(4): e0283827.
• Sonnenschein Leonard, Etyang Tiberious (2024) The Medical Importance of Activated Carbon for Detoxing. Am J Biomed Sci & Res: 21(4).
• Tang WHW, Li DY, Hazen SL (2019) Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol 16(3): 137-154.
• Kaminsky LA, German C, Imboden M, Ozemek C, Peterman JE, et al. (2022) The importance of healthy lifestyle behaviors in the prevention of cardiovascular disease. Prog Cardiovasc Dis 70: 8-15.
• Tan JS, Lin CC, Chen GS (2020) Vasomodulation of peripheral blood flow by focused ultrasound potentiates improvement of diabetic neuropathy. BMJ Open Diabetes Res Care 8(1): e001004.
• Vinik AI (2003) Management of neuropathy and foot problems in diabetic patients. Clin Cornerstone5(2): 38-55.
• Selene M, Scott W, Shirley Z, Leonard S (2023) Phytotherapy Management in a Vaccinated Diabetic Patient with Foot Ulceration and Peripheral Vascular Disease: A Case Study of a Dietary Supplement and Its Effect on Arterial Blood Flow. Am J Biomed Sci & Res 18(5).
• Petzinger GM, Fisher BE, McEwen S, Beeler JA, Walsh JP, et al. (2013) Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease. Lancet Neurol 12(7): 716-26.
• Han PP, Han Y, Shen XY, Gao ZK, Bi X (2023) Enriched environment-induced neuroplasticity in ischemic stroke and its underlying mechanisms. Front Cell Neurosci 17: 1210361.
• Idelevich A, Baron R (2018) Brain to bone: What is the contribution of the brain to skeletal homeostasis? Bone 115: 31-42.
• Patabendige A, Singh A, Jenkins S, Sen J, Chen R (2021) Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke. Int J Mol Sci 22(8): 4280.
• Santoro G, Piccirilli M, Chiarella V, Greco N, Berra LV, et al. (2021) Intracranial capillary hemangiomas: literature review in pediatric and adult population. Neurosurg Rev 44(4): 1977-1985.
• Stubbs MJ, Mouyis M, Thomas M (2018) Deep vein thrombosis. BMJ 360: k351.
• Hemp JH, Sabri SS (2015) Endovascular management of visceral arterial aneurysms. Tech Vasc Interv Radiol 18(1): 14-23.
• Vakili S, Zampella JG, Kwatra SG, Blanck J, Loss M (2019) Lymphocytic Thrombophilic Arteritis: A Review. J Clin Rheumatol 25(3): 147-152.
• Sonnenschein Leonard and Etyang Tiberious, T Cell Activation by Natural Mechanisms. Am J Biomed Sci & Res. 2024(b) 21(6).
• de Souza TSP, de S Pfeiffer PA, do N Pereira J, Pereira Neto EA, Dutra TS, et al. (2022) Immune System Modulation in Response to Strength Training With Blood Flow Restriction. J Strength Cond Res 36(8): 2156-2161.
• Rappaport AM (1980) Hepatic blood flow: morphologic aspects and physiologic regulation. Int Rev Physiol 21:1-63.
• Choi NR, Kim JN, Kwon MJ, Lee JR, Kim SC, et al. (2022) Grape seed powder increases gastrointestinal motility. Int J Medica Sci 19(5): 941-951.
• Turki K, Charradi K, Boukhalfa H, Belhaj M, Limam F, et al. (2016) Grape seed powder improves renal failure of chronic kidney disease patients. EXCLI J 15: 424-433.
• Gupta M, Dey S, Marbaniang D, Paulami Pal, Subhabrata Ray, et al. (2020) Grape seed extract: having a potential health benefits. J Food Sci Technol 57(4): 1205-15
• Foshati S, Nouripour F, Sadeghi E, Reza Amani (2021) The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis. Pharmacol Res 175: 105905.
• Katsuda Y, Niwano Y, Nakashima T, Takayuki Mokudai, Keisuke Nakamura, et al. (2015) Cytoprotective effects of grape seed extract on human gingival fibroblasts in relation to its antioxidant potential. PLoS One 10(8): e0134704.
• Cheah KY, Bastian SE, Acott TM, Suzanne M Abimosleh, Kerry A Lymn, et al. (2013) Grape seed extract reduces the severity of selected disease markers in the proximal colon of dextran sulphate sodium-induced coli­tis in rats. Dig Dis Sci 58(4): 970-977.
• Breuss JM, Atanasov AG, Uhrin P (2019) Resveratrol and Its Effects on the Vascular System. Int J Mol Sci 20(7): 1523.
• Hogan S, Canning C, Sun S, Xiuxiu Sun, Hoda Kadouh, et al. (2011) Dietary supplementation of grape skin extract improves glycemia and inflammation in diet-induced obese mice fed a Western high fat diet. J Agric Food Chem 59: 3035-3041.
• Bagchi D, Swaroop A, Preuss HG, Manashi Bagchi (2014) Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: an overview. Mutat Res 768: 69-73.
• Thomas P, Wang YJ, Zhong JH, Shantha Kosaraju, Nathan J O Callaghan, et al. (2009) Grape seed polyphenols and curcumin reduce genomic instability events in a transgenic mouse model for Alzheimer's disease. Mutat Res 661(1-2): 25-34.
• Khanal RC, Howard LR, Prior RL (2009) Procyanidin content of grape seed and pomace and total anthocyanin content of grape pomace as affected by extrusion processing. J Food Sci 74(6): 174-182.
• Charradi K, Elkahoui S, Karkouch I, Limam F, Ben Hassine F, et al. (2014) Protective effect of grape seed and skin extract against high-fat dietinduced liver steatosis and zinc depletion in rat. Dig Dis Sci 59(8): 1768-1778.
• Charradi K, Elkahoui S, Karkouch I, Limam F, Hassine FB, et al. (2012) Grape seed and skin extract prevents high-fat diet-induced brain lipotoxicity in rat. Neurochem Res 37(9): 2004-2013.
• Charradi K, Elkahoui S, Karkouch I, Limam F, Hamdaoui G, Hassine FB, et al. (2013) Grape seed and skin extract alleviates high-fat diet-induced renal lipotoxicity and prevents copper depletion in rat. Appl Physiol Nutr Metab 38(3): 259-267.
• Bao L, Zhang Z, Dai X, Ding Y, Jiang Y, et al. (2015) Effects of grape seed proanthocyanidin extract on renal injury in type 2 diabetic rats. Mol Med Rep 11(1): 645-652.
• Zhang J, Pan X, Li N, Li X, Wang Y, et al. (2014) Grape seed extract attenuates arsenic-induced nephrotoxicity in rats. Exp Ther Med 7(1): 260-266.
• Gao Z, Liu G, Hu Z, Li X, Jang X, et al. (2014) Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting reticulum stress-induced apoptosis. Mol Med Rep 9(3): 801-807.
• Ulusoy S, Ozkan G, Ersoz S, Orem A, Alkanat M, et al. (2012) The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy. Ren Fail 34(2): 227-234.
• Ulusoy S, Ozkan G, Yucesan FB, Ersoz S, Orem A, et al. (2012) Anti-apoptotic and anti-oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A-induced nephropathy. Nephrology (Carlton) 17(4): 372-379.
• Schwalfenberg GK (2021) N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). Journal of Nutrition and Metabolism 2021: 9949453.
• Gracey M, Burke V, Anderson CM (1969) Treatment of abdominal pain in cystic fibrosis by oral administration of n-acetyl cysteine. Archives of Disease in Childhood 44(235): 404-405.
• Bauerlein DK, Akbar HN, von Rosenvinge EC, Loughry ND, John PR, et al. (2019) Benefit of N-Acetylcysteine in Postoperative Hepatic Dysfunction: Case Report and Review of Literature. Case Reports in Hepatology 2019: 1-4.
• Millea P J (2009) “N-Acetylcysteine: multiple clinical applications,” Am Fam Physician 80(3): 265-269.
• Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A (2017) “A review on various uses of N-acetylcysteine,” Cell J 19(1): 11-17.
• Medina J, Moreno Otero R (2005) Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs 65(17): 2445-2461.
• Ricardo Moreno Otero, María Trapero Marugán (2010) Hepatoprotective effects of antioxidants in chronic hepatitis C. World J Gastroenterol 16(15): 1937-8.
• Tauseef Nabi, Sumaiya Nabi, Nadeema Rafiq, Altaf Shah (2017) Role of N-acetylcysteine treatment in nonacetaminophen-induced acute liver failure: a prospective study. Saudi Journal of Gastroenterology 23(3): 169-175.
• Alla Melhem, Mirela Stern, Oren Shibolet, Eran Israeli, Zvi Ackerman, et al. (2005) “Treatment of CHC virus infection via antioxidants: results of a phase I clinical trial,” J Clini Gastroenterol 39(8): 737-42.
• Yu J, Balaji B, Tinajero M, Jarvis S, Khan T, et al. (2022) White rice, brown rice and the risk of type 2 diabetes: a systematic review and meta-analysis. BMJ open 12(9): e065426.
• Wu F, Yang N, Touré A, Jin Z, Xu X (2013) Germinated brown rice and its role in human health. Crit Rev Food Sci Nutr 53(5): 451-463.
• Reid IR, Bristow SM, Bolland MJ (2015) Calcium supplements: benefits and risks. J Intern Med 278(4): 354-368.
• A Catharine Ross, JoAnn E Manson, Steven A Abrams, John F Aloia, Patsy M Brannon, et al. (2011) The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know. J Clin End Metab 96(1): 53-58.
• Lewicki S, Zdanowski R, Krzyżowska M, Lewicka A, Dębski B, et al. (2014) The role of Chromium III in the organism and its possible use in diabetes and obesity treatment. Annals of agricultural and environmental medicine: AAEM 21(2): 331-335.
• Suksomboon N, Poolsup N, Yuwanakorn, A (2014) Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. Journal of clinical pharmacy and therapeutics 39(3): 292-306.
• Delange F, Lecomte P (2000) Iodine Supplementation: Benefits Outweigh Risks. Drug Safety 22(2): 89-95.
• Leung AM, Pearce EN, Braverman LE (2011) Iodine nutrition in pregnancy and lactation. Endocrinology and metabolism clinics of North America 40(4): 765-777.
• Pickering G, Mazur A, Trousselard M, Bienkowski P, Yaltsewa N, et al. (2020) Magnesium Status and Stress: The Vicious Circle Concept Revisited. Nutrients 12(12): 3672.
• Gröber U, Schmidt J, Kisters K (2015) Magnesium in Prevention and Therapy. Nutrients 7(9): 8199-8226.
• Chen P, Bornhorst J, Aschner M (2018) Manganese metabolism in humans. Front biosci (Landmark edition) 1(23): 1655-1679.
• Horning KJ, Caito SW, Tipps KG, Bowman AB, Aschner M, et al. (2015) Manganese Is Essential for Neuronal Health. Annual review of nutrition 35: 71-108.
• Das P, Tadikonda BV (2020) Bentonite Clay: A Potential Natural Sanitizer for Preventing Neurological Disorders. ACS chem neurosci 11(20): 3188-3190.
• Gomes CSF (2018) Healing and edible clays: a review of basic concepts, benefits and risks. Environ geochem health 40(5): 1739-1765.
• Huang XY, Hu DW, Zhao FJ (2022) Molybdenum: More than an essential element. Journal of experimental botany 73(6): 1766-1774.
• Janet A Novotny, Catherine Peterson A (2018) Molybdenum. Adv nutr 9(3): 272-273.
• Ahmad R, Riaz M, Khan A, Aljamea A, Algheryafi M, et al. (2021) Ganoderma lucidum (Reishi) an edible mushroom; a comprehensive and critical review of its nutritional, cosmeceutical, mycochemical, pharmacological, clinical, and toxicological properties. Phytotherapy research: PTR 35(11): 6030-6062.
• Sohretoglu D, Huang S (2018) Ganoderma lucidum Polysaccharides as An Anti-cancer Agent. Anti-cancer agents in medicinal chemistry 18(5): 667-674.
• Skrajnowska D, Bobrowska Korczak B (2019) Role of Zinc in Immune System and Anti-Cancer Defense Mechanisms. Nutrients 11(10): 2273.
• Saper RB, Rash R (2009) Zinc: an essential micronutrient. American family physician 79(9): 768-772.
• Sonnenschein Leonard, Etyang Tiberious, Shah Rutu, Frischer Ruth, Rein Glen, et al. (2021) The Effect of An Aqueous Electricidal Solution on General Well Being. Am J Biomed Sci & Res: 13(4).
• Glorieux C, Calderon PB (2017) Catalase, a remarkable enzyme: targeting the oldest antioxidant enzyme to find a new cancer treatment approach. Biol chem 398(10): 1095-1108.
• Heck DE, Shakarjian M, Kim HD, Laskin JD, Vetrano AM, et al. (2010) Mechanisms of oxidant generation by catalase. Annals of the New York Academy of Sciences 1203: 120-125.
• Elena Jimenez Negro, Jandirk Sendker, Timo Stark, Bartosz Lipowicz, Andreas Hensel (2022) Phytochemical and functional analysis of horseradish (Armoracia rusticana) fermented and non-fermented root extracts. Fitoterapia 162: 105282.
• Lee TH, Yoon DH, Park KJ, Hong SM, Kim M, et al. (2023) Neurotrophic phenolic glycosides from the roots of Armoracia rusticana. Phytochemistry 216: 113886.
• Jong Eel Park, Tae Hyun Lee, Song Lim Ham, Lalita Subedi, Seong Min Hong (2022) Anticancer and Anti-Neuroinflammatory Constituents Isolated from the Roots of Wasabia japonica. Antioxidants (Basel) 11(3): 482.
• Kim CS, Subedi L, Kwon OW, Park HB, Kim SY, et al. (2016) Wasabisides A-E, Lignan Glycosides from the Roots of Wasabia japonica. Journal of natural products 79(10): 2652-2657.
• Klein AV, Kiat H (2015) Detox diets for toxin elimination and weight management: a critical review of the evidence. J Hum Nutr Diet 28(6): 675-686.
• Li M, Wang H, Tian L, Pang Z, Yang Q, et al. (2022) COVID-19 vaccine development: milestones, lessons and prospects. Signal Transduct Target Ther 7(1): 146.
• Zhu H, Zhao H, Zhang L, Xu J, Zhu C, et al. (2017) Dandelion root extract suppressed gastric cancer cells proliferation and migration through targeting lncRNA-CCAT1. Biomed Pharmacothe 93: 1010-1017.
• Grosshagauer S, Kraemer K, Somoza V (2020) The True Value of Spirulina. J Agric Food Chem 68(14): 4109-4115.
• AlFadhly NKZ, Alhelfi N, Altemimi AB, Verma DK, Cacciola F, et al. (2022) Trends and Technological Advancements in the Possible Food Applications of Spirulina and Their Health Benefits: A Review. Molecules 27(17): 5584.
• Kocaadam B, Şanlier N (2017) Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Critical reviews in food science and nutrition 57(13): 2889-2895.
• Zhang HA, Kitts DD (2021) Turmeric and its bioactive constituents trigger cell signaling mechanisms that protect against diabetes and cardiovascular diseases. Mol Cell Biochem 476(10): 3785-3814.
• Cohen JN, Kuikman MA, Politis Barber V, Stairs BE, Coates AM, et al. (1985) Blood flow restriction and stimulated muscle contractions do not improve metabolic or vascular outcomes following glucose ingestion in young, active individuals. J Appl Physiol 133(1): 75-86.
• Meyer C, Schwaiger M (1997) Myocardial blood flow and glucose metabolism in diabetes mellitus. Am J Cardiol 80(3A): 94A-101A.
• Khalid M, Petroianu G, Adem A (2022) Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives. Biomolecules 12(4): 542.
• Singh R, Barden A, Mori T, Beilin L (2001) Advanced glycation end-products: a review. Diabetologia 44(2): 129-1246.
• Alizargar J, Bai CH, Hsieh NC, Wu SV (2020) Use of the triglyceride-glucose index (TyG) in cardiovascular disease patients. Cardiovasc Diabetol 19(1): 8.
• Faselis C, Katsimardou A, Imprialos K, Deligkaris P, Kallistratos M, et al. (2020) Microvascular Complications of Type 2 Diabetes Mellitus. Curr Vasc Pharmacol 18(2): 117-124.
• Mishriky BM, Cummings DM (2022) Powell JR. Diabetes-Related Microvascular Complications - A Practical Approach. Prim Care 49(2): 239-254.
• Bahare Salehi, Yakup Berkay Yılmaz, Gizem Antika, Tugba Boyunegmez Tumer, Mohamad Fawzi Mahomoodally, et al. (2019) Insights on the Use of α-Lipoic Acid for Therapeutic Purposes. Biomolecules 9(8): 356.
• Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM, et al. (2009) Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochimica et biophysica acta 1790(10): 1149-1160.
• Husain I, Zameer S, Madaan T, Minhaj A, Ahmad W, et al. (2019) Exploring the multifaceted neuroprotective actions of Emblica officinalis (Amla): a review. Metabolic brain disease 34(4): 957-965.
• Kanthe PS, Patil BS, Bagali SC, Reddy RC, Aithala MR, et al. (2017) Protective effects of Ethanolic Extract of Emblica officinalis (amla) on Cardiovascular Pathophysiology of Rats, Fed with High Fat Diet. Journal of clinical and diagnostic research: JCDR 11(9): CC05-CC09.
• Ny V, Houška M, Pavela,R, Tříska J (2021) Potential benefits of incorporating Astragalus membranaceus into the diet of people undergoing disease treatment: An overview. J Funct Foods 77: 104339.
• Fu J, Wang Z, Huang L, Zheng S, Wang D, et al. (2014) Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother res 28(9): 1275-1283.
• Setiyorini E, Qomaruddin MB, Wibisono S, Juwariah T, Setyowati A, et al. (2022) Complementary and alternative medicine for glycemic control of diabetes mellitus: A systematic review. Journal of public health research 11(3): 22799036221106582.
• Alam MA, Uddin R, Subhan N, Rahman MM, Jain P, et al. (2015) Beneficial role of bitter melon supplementation in obesity and related complications in metabolic syndrome. Journal of lipids 2015: 496169.
• Gruenwald J, Freder J, Armbruester N (2010) Cinnamon and health. Crit rev food sci nutr 50(9): 822-834.
• Singletary K (2019) Cinnamon: Update of Potential Health Benefits. Nutrition Today 54(1): 42-52.
• Haber SL, Keonavong J (2013) Fenugreek use in patients with diabetes mellitus. Am j health syst 70(14): 1196-1203.
• Kim J, Noh W, Kim A, Choi Y, Kim YS, et al. (2023) The Effect of Fenugreek in Type 2 Diabetes and Prediabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. International journal of molecular sciences 24(18): 13999.
• Martínez Solís I, Acero N, Bosch Morell F, Castillo E, González Rosende ME, et al. (2019) Neuroprotective Potential of Ginkgo biloba in Retinal Diseases. Planta medica 85(17): 1292-1303.
• Biernacka P, Adamska I, Felisiak K (2023) The Potential of Ginkgo biloba as a Source of Biologically Active Compounds-A Review of the Recent Literature and Patents. Molecules 28(10): 3993.
• Horne JA, Reyner LA (2001) Beneficial effects of an "energy drink" given to sleepy drivers. Amino acids 20(1): 83-89.
• Carmen Rubio, Montaña Cámara, Rosa María Giner, María José González Muñoz, Esther López García, et al. (2022) Caffeine, D-glucuronolactone and Taurine Content in Energy Drinks: Exposure and Risk Assessment. Nutrients 14(23: 5103.
• Khan F, Sarker MMR, Ming LC, Mohamed IN, Zhao C, et al. (2019) Comprehensive Review on Phytochemicals, Pharmacological and Clinical Potentials of Gymnema sylvestre. Frontiers in pharmacology 10: 1223.
• Tiwari P, Mishra BN, Sangwan NS (2014) Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. Biomed Res Int 2014: 830285.
• Gelber D, Levine J, Belmaker RH (2001) Effect of inositol on bulimia nervosa and binge eating. Int j eat disord 29(3): 345-348.
• Genazzani AD, Prati A, Santagni S, Ricchieri F, Chierchia E, et al. (2012) Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients. Gynecological 28(12): 969-973.
• Maryam Khalid Rizvi, Roshina Rabail, Seemal Munir, Muhammad Inam Ur Raheem, Mir Muhammad Nasir Qayyum, et al. (2022) Astounding Health Benefits of Jamun (Syzygium cumini) toward Metabolic Syndrome. Molecules (Basel) 27(21): 7184.
• Francesca Raffaelli, Francesca Borroni, Alessandro Alidori, Giacomo Tirabassi, Emanuela Faloia, et al. (2015) Effects of in vitro supplementation with Syzygium cumini (L.) on platelets from subjects affected by diabetes mellitus. Platelets 26(8): 720-725.
• Turck D, Castenmiller J, De Henauw S, Hirsch Ernst KI, Kearney J, et al. (2018) Magnesium citrate malate as a source of magnesium added for nutritional purposes to food supplements. EFSA 16(12): e05484.
• Uysal N, Kizildag S, Yuce Z, Guvendi G, Kandis S, et al. (2019) Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best? Biol Trace Elem Res 187(1): 128-136.
• Mahmoud MF, Abdelaal S, Mohammed HO, El Shazly AM, Rachid Daoud, et al. (2021) Syzygium jambos extract mitigates pancreatic oxidative stress, inflammation and apoptosis and modulates hepatic IRS-2/AKT/GLUT4 signaling pathway in streptozotocin-induced diabetic rats. Biomedicine & pharmacotherapy 142: 112085.
• Melvin Adhiambo Ochieng, Widad Ben Bakrim, Gabin Thierry M Bitchagno, Mona F Mahmoud, Mansour Sobeh (2022) Syzygium jambos L. Alston: An Insight Into its Phytochemistry, Traditional Uses, and Pharmacological Properties. Front pharmaco 13: 786712.
• Patil SM, Shirahatti PS, Ramu R (2022) Azadirachta indica A. Juss (neem) against diabetes mellitus: a critical review on its phytochemistry, pharmacology, and toxicology. The J pharm pharmacol 74(5): 681-710.
• Olakunle Sanni, Ochuko L Erukainure, Chika I Chukwuma, Neil A Koorbanally, Collins U Ibeji, et al. (2019) Azadirachta indica inhibits key enzyme linked to type 2 diabetes in vitro, abates oxidative hepatic injury and enhances muscle glucose uptake ex vivo. Biomed Pharmacother 109: 734-743.
• Elkhalifa AEO, Alshammari E, Adnan M, Alcantara JC, Awadelkareem AM, et al. (2021) Okra (Abelmoschus Esculentus) as a Potential Dietary Medicine with Nutraceutical Importance for Sustainable Health Applications. Molecules 26(3): 696.
• Chiung Huei Peng, Yaw Bee Ker, Hsin Hua Li, Sing Hua Tsou, Chih Li Lin, et al. (2022) Abelmoschus esculentus subfractions ameliorate hepatic lipogenesis and lipid uptake via regulating dipeptidyl peptidase-4-With improving insulin resistance. PloS one 17(3): e0265444.
• Juárez Rojop IE, Díaz Zagoya JC, Ble Castillo JL, Miranda Osorio PH, Castell Rodríguez AE, et al. (2012) Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats. BMC complementary and alternative medicine 12: 236.
• Sharma A, Sharma R, Sharma M, Kumar M, Barbhai MD, et al. (2022) Carica papaya L. Leaves: Deciphering Its Antioxidant Bioactives, Biological Activities, Innovative Products, and Safety Aspects. Oxidative medicine and cellular longevity 2022: 2451733.
• Šic Žlabur J, Bogdanović S, Voća S, Skendrović Babojelić M (2020) Biological Potential of Fruit and Leaves of Strawberry Tree (Arbutus unedo L.) from Croatia. Molecules 25(21): 5102.
• El Haouari M, Assem N, Changan S, Kumar M, Daştan SD, et al. (2021) An Insight into Phytochemical, Pharmacological, and Nutritional Properties of Arbutus unedo L. from Morocco. Evid based complement alternat med 2021: 1794621.
• Baliou S, Adamaki M, Ioannou P, Pappa A, Panayiotidis MI, et al. (2021) Protective role of taurine against oxidative stress (Review). Molecular medicine reports 24(2): 605.
• Tawar Qaradakhi, Laura Kate Gadanec, Kristen Renee McSweeney, Jemma Rose Abraham, Vasso Apostolopoulos, et al. (2020) The Anti-Inflammatory Effect of Taurine on Cardiovascular Disease. Nutrients 12(9): 2847.
• Volkov I, Press Y, Rudoy I (2006) Vitamin B12 could be a "master key" in the regulation of multiple pathological processes. Journal of Nippon Medical School. Nippon Ika Daigaku zasshi 73(2): 65-69.
• Cassiano LMG, Cavalcante Silva V, Oliveira MS, Prado BVO, Cardoso CG, et al. (2023) Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic markings. Frontiers in immunology 14: 1048790.
• Wuerch E, Urgoiti GR, Yong VW (2023) The Promise of Niacin in Neurology. Neurotherapeutics 20(4): 1037-1054.
• Gasperi V, Sibilano M, Savini I, Catani MV (2019) Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications. Int j Mol Sci 20(4): 974.
• Erdman JW, Macdonald IA, Zeisel SH (Eds.) (2012) Pantothenic acid. In Present Knowledge in Nutrition (10th ed., pp. 375-390) Wiley-Blackwell.
• Ragaller V, Lebzien P, Südekum KH, Hüther L, Flachowsky G, et al. (2011) Pantothenic acid in ruminant nutrition: a review. J anim physiol anim nutr 95(1): 6-16.
• Hui Wang, Yansong Xue, Hanying Zhang, Yan Huang, Guan Yang, et al. (2013) Dietary grape seed extract ameliorates symptoms of inflammatory bowel disease in IL10-deficient mice. Mol Nutr Food Res 57(12): 2253-2257.