Have you ever experienced butterflies in the stomach before an important meeting? Does attempting to “cure” the blues with Ben and Jerry’s sound familiar? If so, then you are already acquainted with the existence of a connection between our moods and our gut. Indeed, the brain and the digestive system are linked by complex pathways where information flows back and forth on a continual basis: certain feelings and thoughts can stimulate an exaggerated gut response, while sensitized nerves in the gut can trigger changes in the brain. The Nervous System and the “Second Brain” The nervous system is a complex
Metabolic dysfunctions are a major risk factor for cardiovascular incidents such as myocardial infarction, stroke, and non-ischemic cardiovascular disease1. The constellation of symptoms indicative of metabolic dysfunction include: central obesity (apple body types), glucose intolerance, insulin resistance (eg. non-insulin-dependent diabetes mellitus), hypertension, dyslipidemia, high markers of inflammation, and poor blood clotting (hyperfibrinolysis). Given the complexity of this syndrome, identifying and developing treatments can be very difficult. As we learn more, we gain a greater understanding about how we can approach the underlying cause of metabolic dysfunctions while managing the symptoms.Given the wide array of symptoms, metabolic syndrome was often overlooked in the past, though more recently the following criteria have been established, with three of the five required for diagnosis:
Innovative treatments can target one or more physiological process in the body and have a significant overall impact. We explore these processes and how AOR has redefined the approach to managing and preventing many aspects of this complex syndrome, using research to guide the development of novel, multi-targeted products.
Insulin Insensitivity and Glucose Dysregulation
With every meal that we eat, our bodies break down the carbohydrate portion of the meal into simple sugars such as glucose, which can then be used for energy or stored as fat for a later time. Unfortunately, a poor diet and lifestyle can lead to poorly controlled blood sugar, impaired insulin production and eventually type 2 diabetes2. In addition to the increased cardiovascular risk, glucose dysregulation produces inflammation, toxins and damage to the cells of the body which accelerates aging, weight gain and skin disorders, and reduces life span2.
Blood Sugar Disorders
In Type I Diabetes Mellitus (T1DM), the immune system is attacking the pancreas’s insulin-producing cells. This leads to the inability to produce adequate levels of insulin, and without the presence of insulin, blood sugar levels rise uncontrollably3. These patients require additional insulin to regulate their blood glucose levels.
The more common form, Type II Diabetes Mellitus (T2DM), usually develops in late adulthood, and is primarily the result of increased insulin resistance. Insulin resistance refers to the inability of our cells to respond to insulin even when normal levels of insulin are present. Once cells become insulin resistant, glucose cannot enter cells and blood glucose levels rise3,4
Cardiovascular Complications of Unstable Blood Sugar Levels
People with chronically elevated blood sugar levels are twice as likely to suffer from cardiovascular disease, and five times more likely to experience a cardiovascular incident. In fact, 75% of diabetic deaths result from coronary heart disease1,2. Insulin resistance may also give rise to the other cardiovascular risk factors attributed to metabolic syndrome, such as lower HDL levels, abdominal obesity, higher triglyceride levels, and elevated LDL levels4,5,6.
Other common complications of having unstable blood sugar levels include: retinal damage, blindness (this constitutes 8% of blindness cases in the US), unhealthy blood pressure levels (73% of persons with blood sugar disorders have elevated blood pressure), neuropathy (affecting 60-70% of patients with blood sugar disorders), unhealthy blood vessels, dental disease, increased susceptibility to infections, stroke, kidney failure (main cause of dialysis in developed countries) and ulcer formation, which can lead to tissue damage and amputation (one amputation every 30 seconds worldwide)5,6.
In some patients, especially earlier in the disease process, exercise, dietary changes, and weight loss may restore insulin sensitivity and normalize blood sugar levels. Patients that control their blood sugar levels minimize the damage to their organs (mainly kidneys, blood vessels and eyes) and their incidence of complications is significantly reduced to near normal levels7.
Using a Classic Approach for a New Problem
The pillar of disease prevention is the maintenance of normal tissue and optimal metabolic function. In essence, disease prevention efforts attempt to extend life through healthy lifestyle and dietary habits which in turn maintain strong blood vessels, encourage normal cellular differentiation, give rise to optimal cognition and promote normal metabolism and blood sugar levels.
The benefits of natural treatments with demonstrated efficacy in the maintenance of normal blood glucose levels should not be overlooked.
In 1999 AOR brought the world its first R-Lipoic Acid supplements, containing the genuine orthomolecular form rather than a hybrid of natural and synthetic forms found in conventional “lipoic acid” or “alpha-lipoic acid” supplements12. At the time research was being done on the benefits of high doses of this powerful antioxidant on blood sugar regulation and nerve repair in healthy and diabetic subjects. However, it took some time to convey to the natural health industry the importance of the form (ie. the R form vs. the S form) when supplementing with lipoic acid. Given that R-lipoic acid is now a staple in many blood glucose management plans, this product stands out as a shining example of AOR’s forward-thinking approach.
Other Causes that can Lead to Blood Glucose Dysregulation
1. Environmental Chemical Exposure: A dose-response relationship has been found between low-level exposure to persistent organic pollutants (POPs) and the prevalence of diabetes. POPs, such as DDT and PCBs in plastics, are chemicals that do not easily break down and that bio-accumulate within the environment, and potentially in the body8.
2. Poor Gut Bacteria: Animal studies have shown that the administration of prebiotics can improve metabolic parameters (such as insulin resistance), just as antibiotic administration in diabetic subjects can improve blood sugar regulation9. This suggests that an imbalance in gut bacteria may need to be addressed in diabetic individuals.
3. Genetics: Although genetics cannot be entirely to blame for the development of T2DM, they do play a strong role in predisposing an individual to the condition. For example, individuals with one parent who has T2DM have a 40% risk of developing the condition. If both parents have T2DM, the risk jumps to 70%10.
4. Stress: Evidence exists to show that high levels of stress can contribute to the onset of T2DM. Moreover, it is well-known that stress can elevate blood sugar levels in those already diagnosed with T2DM, and can destabilize blood sugars for hours afterwards11.
The next evolution in creating a product to support normal and healthy blood glucose levels required AOR’s research and development team to take a more multi-targeted approach, combining the benefits of key vitamins and minerals with traditional herbs.
Here are some of the stand out herbs:
Gymnema sylvestre is an herb belonging to the Asclepiadacea family and has an established history of use within the Ayurvedic tradition of India, where it is used for the treatment of diabetes, high cholesterol levels, and obesity. In fact, in Hindi, gymnema is also known as gurmar, which literally means “sugar destroyer”. The main active constituent of gymnema is believed to be gymnemic acid, which is a mixture of at least 17 different saponins13.
The hypoglycemic effect of this herb was scientifically tested for the first time in 1930. Results of human clinical trials with gymnema are very promising. In one open trial, 65 type I and II diabetics were given 400 mg of Gymnema sylvestre extract twice per day for 90 days. In the study, preprandial (before eating) blood glucose levels and postprandial (after eating) blood glucose levels decreased by 11% and 13% respectively compared to baseline14. Amazingly, gymnema seems to be beneficial for both type I and type II diabetics. The gymnema extract appeared to enhance the body’s own insulin, possibly by regenerating or repairing beta cells which produce insulin, as shown in animal studies16,17.
Momordica charantia: Bitter Melon
Momordica charantia, commonly known as bitter melon, is a fruit from the Cucurbitaceae family that is found in tropical areas throughout the world. It has been known as a ‘healing food’ in traditional circles. Bitter melon is exceptionally dense with micronutrients known for their hypoglycemic effects, including charantin, cucurbutanoids, momordicin, oleanolic acids, and insulin-like peptide (plant (p)-insulin), the latter being structurally similar to bovine insulin. Other micronutrients found in M. charantia include: vitamins A and C, beta-carotene, iron, phosphorus, and potassium17.
Studies have also examined its effects in regulating blood sugar, suggesting that the form and preparation of the bitter melon is important for optimizing therapeutic benefit. Fresh juice from the bitter melon rather than the dried fruit seems to result in a greater reduction in fasting and postprandial blood glucose levels17,18.The effectiveness of bitter melon has been examined in both type I and type II diabetes. Scientists have determined that the mechanisms of action responsible for these effects include increasing glucose utilization by the liver, inhibiting gluconeogenesis (glucose production from non-carbohydrate sources), and improving glucose oxidation17,18,19.
Chromium is an essential mineral for the metabolism of carbohydrates. It is an integral component of a complex known as the “glucose tolerance factor”, and a deficiency in this mineral has been associated with reversible insulin resistance and diabetes20,21,22. Chromium increases the sensitivity of insulin receptors, which increases the cellular transport of glucose and reduces blood sugar levels.A large meta-analysis examined the effects of chromium on diabetes across 41 clinical trials. These trials employed doses ranging from 200 to 1000 mcg of chromium, taken over the course of 2 to 26 weeks. Overall, studies have demonstrated that chromium supplementation lowers blood glucose levels, reduces hemoglobin A1C concentrations (a blood marker of diabetes), and improves cholesterol levels22.
Cinnamon mimics and amplifies the effects of insulin, helps to regulate blood glucose and improves glucose utilization22,23,25. Cinnamon contains a compound known as the cinnamon methylhydroxychalcone, which is capable of up-regulating glucose uptake and glycogen synthesis by cells. Both processes are essential for blood sugar regulation26. Two human studies in diabetics have shown a significant improvement with cinnamon supplementation. In the first study, blood glucose levels dropped by 18-29%, triglyceride levels were reduced by 23-30%, LDL cholesterol was lowered by 7-27% and total cholesterol was lowered by 26% after 40 days of cinnamon supplementation in patients with poorly controlled type 2 diabetes23. In the second study, 4 months of supplementation with a cinnamon extract in diabetes patients led to a moderate but significant reduction in blood glucose levels. Decreases in blood sugar were above and beyond the reductions achieved through diet and medication alone24,25.
In recent years attention has shifted from total fat to the distribution of fat on a person’s body. The classic “apple-shaped” body type, with the majority of weight carried centrally on the torso (as opposed to lower on the hips) has been implicated as a risk factor for cardiovascular disease. While this correlation was discovered some time ago, theories into the exact mechanism behind the increase in risk are still being investigated. A leading theory is that central obesity is indicative of increased visceral fat (fat surrounding the organs), which is often highly metabolically active. This type of fat releases free fatty acids and pro-inflammatory cytokines28, increasing the burden on the liver and cardiovascular system. Obesity is also closely related to insulin resistance and is one of the main risk factors for the development of blood sugar disorders1,2,28.
As mentioned earlier, dyslipidemia is part of the diagnostic criteria for metabolic syndrome, but what does that mean exactly? Simply put, it means high triglycerides, low HDL cholesterol, and/or high LDL cholesterol. In order to understand the implications of dyslipidemia, we must first understand the role of cholesterol and lipids in the body and how they can become dysregulated.
Cholesterol, an animal sterol, is a waxy substance found in every cell in our body. Cholesterol is used as a base for the production of steroid hormones, bile salts, vitamin D, as well as maintaining cell membrane fluidity. Without cholesterol we would not be able to properly digest foods, our cell structure would not be able to withstand any changes in temperature, and a significant number of important hormones such as estrogen and testosterone could not be produced29.Our cholesterol is produced in the liver from the molecule acetyl coenzyme A. A key step in this process is a conversion that is controlled by the enzyme HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase. This enzyme can block the production of cholesterol, making it an important target for cholesterol-lowering drugs called statins. However, it also controls the production of many other molecules such as co-enzyme Q10. That’s why there are so many side effects of taking statin drugs. Nearly 10-12% of patients on statin drugs will experience statin-induced muscle pain. Other potential adverse reactions to statin drug use include elevated liver enzymes, lung disease, and in a small subset of patients, increased risk for type 2 diabetes mellitus29,30.
The majority of cholesterol in the body is synthesized, recycled, and degraded in the liver. Cholesterol molecules are transported from the gut to the liver via the lymph in complexes called chylomicrons. Upon arrival at the liver it is repackaged into various lipoprotein complexes which “chaperone” it around the body. There are a number of different lipoprotein complexes, which are classified based on their ratio of proteins to fat and cholesterol. Low density lipoproteins (LDL), very low density lipoproteins (vLDL) and chylomicrons all have very high fat and cholesterol content as compared with the protein-rich high density lipoprotein (HDL). LDL takes the cholesterol to the various tissues, and HDL brings cholesterol back to the liver when we have too much. Once packaged into vLDL, the cholesterol enters circulation and some of it is deposited to the tissues along with fatty acids. Once the cholesterol is deposited, the LDL complexes should be taken up by liver cells after attaching to the LDL receptor on their surface. Meanwhile HDL scavenges blood vessels and tissues for free-form excess cholesterol. It then returns to the liver where the cholesterol can be excreted through the bile or recycled29.
What to Look for in Cooking Oils
1. Saturated vs. unsaturated refers to the number of double bonds on the fatty acid chains. When an oil is composed of unsaturated fatty acids it has multiple double bonds, which causes kinking in the chain making it harder for the chains to pack close together. Like oil in a car, it should flow even when it’s cold, rather than pack together, clump up and get stuck. Unsaturated oils are usually liquid at room temperature and can solidify when cooled (how quickly this happens depends on the number of double bonds present).
2. Configuration – unsaturated fatty acids can either be oriented in a cis-configuration (meaning branches are on the same side of the chain) or a trans-configuration (branches are on opposite sides). The trans-configuration is usually the result of partial hydrogenation during oil production, and is not the natural structure, and it allows for closer packing of fatty acid chains. It has also been well documented that this increases risk for cardiovascular disease.
3. Number of Double Bonds – unsaturated fatty acids may have one double bond (monounsaturated fatty acids or MUFA) or many (polyunsaturated fatty acids or PUFA.) Both MUFA (such as avocado and olive oil) and PUFA (such as fish oils or omega-3 fatty acids from algae) have shown cardiovascular benefits including increasing HDL, reducing LDL and total cholesterol, improving brain function and much more. High heat can break apart some of these double bonds so they are best consumed cold.
4. Length of fatty acid chains- whether saturated or unsaturated, the length of the chain is also associated with different health benefits. Coconut oil has more short and medium chain fatty acids that can tolerate heat exposure, as opposed to oils with longer chains such as olive oil which become degraded by heat exposure.
5. Potential to form harmful oxides- some oils can form harmful, even carcinogenic oxides when heated. For example, sunflower oil produces two times more harmful oxides than olive oil when heated for the same amount of time at the same temperature.
6. What else is in the oil? Coconut oil has molecules called tocotrienols, polyphenols, and tocopherols which give it antioxidant protection, while palm oil is richer in tocotrienols only, and soy oil primarily has tocopherols. Both tocopherols and tocotrienols are the molecules that form the Vitamin E complex – and both groups of molecules have health benefits though they are best when combined. The best oils have a diverse range of beneficial, biologically active, compounds that can mitigate some of the negative effects of by-products that are formed by heating.
Cholesterol and Cardiovascular Health:
High total cholesterol, triglycerides, LDL, and trans fats are linked to an increased risk of cardiovascular events such as heart attacks and strokes29,30. Cholesterol can build up due to increased production, increased consumption, or decreased excretion. The cause of the build-up as well as the form of cholesterol in the plasma is important when determining risk and plan of action for treatment.
Genetic disorders can affect the LDL receptors on the surface of liver cells, causing an increased amount of LDL in circulation. High LDL levels in circulation lead to an increased risk of cardiovascular events irrespective of diet and lifestyle in these patients. However, these genetic causes are responsible for only a small percentage of the population diagnosed with high cholesterol. The majority of cases in North America can be linked to diet and lifestyle31.
Increased consumption of cholesterol-rich foods results in increased levels of LDL in circulation. Excess LDL can attach onto and infiltrate the walls of blood vessels. When this happens, it results in the formation of a reactive oxidative species (a type of free radical) that attracts immune cells. White blood cells begin to congregate and an inflammatory cascade is initiated. As more and more cells are attracted to this middle layer of the blood vessel, arterial plaque can begin to disrupt blood flow and may eventually fully block the vessel, or a piece of the plaque can rupture and travel throughout the body. All of these scenarios can have very serious consequences for cardiovascular health31.
The “arthrogenic triad” are a trio of lab findings that show an increased risk for the development of atherosclerosis (or hardening of arteries) – this includes high serum LDL, low HDL, and high triglycerides31. Further, risks are increased with low fiber diets as this prevents the excretion of cholesterol. An inactive lifestyle can also increase the risk of the LDL adhering to the blood vessels.
Managing Healthy Cholesterol Levels Naturally:
Since HDL is able to scavenge for excess cholesterol in tissues and in circulation to take back to the liver for excretion, it is an important target for the treatment of dyslipidemia. Certain types of healthy fats in the diet such as unsaturated, non-trans fats like olive oil or fish oil can promote HDL, while saturated and trans-fats increase the LDL content.
HDL can increased by eating more good fats particularly those that are unsaturated, non-trans, with one or more double bond present, like olive or fish oils.
HDL can also be increased through supplementation with various nutrients and herbs. For example, a traditional Chinese approach to dyslipidemia is the consumption of Red Yeast Rice (RYR). RYR is a reddish-purple rice that is fermented with the yeast Monascus purpureus, from which it obtains its colour and taste. RYR extracts contain numerous active ingredients such as GABA, monascin, ankaflavin, dimerumic acid, and various monacolins32. Monacolin K (MK) – a specific form of monacolin, is unique because it is a naturally occurring statin, chemically identical to lovastatin. Although they share the same properties, lovastatin was patented as a pharmaceutical drug and is known by its brand name Mevacor (Merck & Co.)33. Monacolin K, on the other hand, has become a controversial non-prescription ingredient used in supplements that is surprisingly still found in most RYR extracts even though many regulatory bodies prohibit it.
Keeping in mind that almost all RYR supplements contain monacolin K, they therefore carry the same side effect risks as many statin medications. However, a number of studies using RYR have found that its positive effects on cholesterol cannot be explained solely by the monacolin K content and instead are due to a combination of its active ingredients. In fact, Monocolin K-free red yeast rice has demonstrated the ability to favorably affect cholesterol levels, without the side effects of Monacolin K, in numerous clinical studies. Monascin and ankaflavin appear to be the most important active ingredients in this process35. Most RYR products also contain a harmful by-product of the fermentation process known as citrinin, which has been linked with kidney and liver toxicity34. With this in mind, a new patented RYR blend was born, known as RYR Ankascin -568-R™ .This patented blend is guaranteedto be free from monacolin K and citrinin, offering a safer alternative to other red yeast rice products on the market, with no reduction in levels of coenzyme Q10. RYR Ankascin-568-R™ has successfully completed two human clinical trials for cholesterol regulation with additional studies underway36.
In regards to its specific effect on blood lipids, three distinct mechanisms of action have been identified:
1. Higher LDL cholesterol influx into the liver, meaning lower LDL values in the blood
2. Higher cholesterol excretion in bile acids, meaning lower total cholesterol
3. Increased HDL levels
Another exciting development in blood lipid regulation was discovered when investigating the effects of supplementation with a standardized bergamot extract on various cholesterol parameters. This citrus fruit is found in earl grey tea, and is the ingredient responsible for its distinctive flavor. Multiple studies have focused on bergamot’s beneficial effects on total cholesterol, LDL, HDL, triglycerides, blood sugar, and markers of oxidative stress37. It was studied in high cholesterol patients, those with fatty liver disease, metabolic syndrome, and in conjunction with statin drugs38,39.
According to the Heart and Stroke Foundation of Canada, the incidence of high blood pressure rose 77% among Canadians between 1994 and 2005, based on patients’ own reports40. Commonly, medical textbooks have stated that a blood pressure reading of 120/80 is considered normal. Research indicates that a “high” blood pressure of 140/90 is a risk factor for stroke, coronary artery disease, and kidney disease. Each increase of 20 mmHg in systolic blood pressure and 10 mmHg in diastolic blood pressure, over the range of 115/75 to 185/115, doubles the risk of a fatal coronary event41. Elevated blood pressure alters vascular compliance and endothelial function and can lead to calcification of the arteries. There are a number of factors that can cause increases in blood pressure, such as40:
• Diet (particularly a high salt intake)
• Hydration imbalance
• Lack of exercise
• Caffeine intake
• Alcohol intake
• Stress management
Conventional pharmaceuticals which manage blood pressure are one of the most common prescriptions given today. Common side effects from these medications include42:
• Diuretics – weakness, fatigue, leg cramps, erectile dysfunction
• Beta blockers – asthmatic symptoms, cold hands/feet, depression, insomnia, erectile dysfunction
• Angiotensin converting enzyme (ACE) inhibitors – dry cough, skin rash, loss of taste
• Angiotensin receptor blockers (ARB) – dizziness
• Calcium channel blockers- constipation, dizziness, headache, palpitations, swollen ankles
The class of drugs called ACE inhibitors are associated with certain side effects as mentioned above, as well as some long term consequences, including renal impairment. However, novel interventions that target this RAAS pathway could revolutionize the current treatment model for hypertension as we know it.
The scientific community is turning its attention to new findings which could place pea protein as a natural alternative to ACE inhibitors. Professor Rotimi Aluko and his research team at the University of Manitoba, in Winnipeg, have discovered a process to hydrolyze and fraction protein from peas, using food grade enzymes and a patented process. The result is a product which can reduce blood pressure while maintaining healthy kidney function by decreasing the activity of renin. Pea protein hydrolysate (PPH) is a peptide extract with health promoting activities and no known side effects43,44.The unique feature of this peptide is that unlike typical ACE inhibitors, PPH is a specific renin inhibitor and patients are less likely to develop a tolerance. Moreover, this peptide has been shown to be effective in polycystic kidney disease which is common in the West and offers another approach to dealing with this disease.
Most of the demonstrated health benefits seemed to be derived from hydrolysed proteins, which are proteins that have been broken down into specific peptides. Ingestion of pea protein was also related to an increase in nitric oxide, which results in relaxation and dilation of the blood vessels, thereby reducing blood pressure. Further, pea protein exhibits moderate antioxidant activity. All of these beneficial effects help provide new hope for those suffering from hypertension.
It is clear to see how complex each aspect of this syndrome is. As we explore these complexities we can also develop new tools for treatment. As they say, “knowledge is power.
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