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The Top 5 Supplements for Diabetic Peripheral Neuropathy A Special Report by Robert Creighton DPM Introduction Thank you for your interest in this special report. I hope it is helpful to you. One of my areas of interest involves the use of food, movement, lifestyle, and nutritional supplements for people with diabetes and pre-diabetes metabolic syndrome. This report is an extension of that interest. Diabetes is a disease that causes abnormal levels of sugar in the blood. Those of you who are diabetic know it is a constant effort to maintain healthy blood sugars. Unfortunately, over time increased blood sugar levels damage the body. This becomes especially evident in your cardiovascular system including the blood vessels of the heart, kidneys, brain, and feet. As a foot and ankle specialist, treating a part of the body that is especially impacted by the diabetes and prediabetes epidemics, I see the effects of unhealthy blood sugar levels on a daily basis. What many people do not realize is that the number of people with prediabetes, also known as metabolic syndrome or syndrome x, is also very high and steadily increasing. The increasing number of adults who have this condition is linked to the rise in obesity rates. It is very likely metabolic syndrome will overtake smoking as the leading risk factor for heart disease.1 Do You Have Metabolic Syndrome? According to the National Institutes of Health, metabolic syndrome is diagnosed if you have at least three of the risk factors below (or you are on medicine to treat the risk factors). A large waistline An elevated triglyceride level A reduced HDL-cholesterol level Elevated blood pressure Elevated fasting blood sugar levels Do you know someone with prediabetes metabolic syndrome? This special report discusses the use of supplements to assist with the management of a very difficult problem faced by many diabetics and prediabetics alike – the nerve damage of the feet and legs known as diabetic peripheral neuropathy. In this report I will just refer to diabetic peripheral neuropathy as “DPN” for short. DPN can be a very agonizing condition. I have put together this special report on various supplements that have shown some ability to assist people with diabetes and pre-diabetes in the area of foot and leg nerve health because I see so many people with this difficult problem who need all the help they can get. I have focused on supplements that have shown some supportive role for the health of the nerves in the feet and legs. Much of this information not only applies to people with diabetes and pre-diabetes, but for all who wish to pursue their best health. Proper blood sugar management in the diabetic involves medication, proper diet, a healthy lifestyle, and at least some form of exercisemovement. Do not think you can control your diabetes or pre-diabetes with a diet supplement! You should also understand that you can take “too much of a good thing” with supplements – do not use a more-is-better approach. Vitamin and nutrient supplements have many roles beyond helping to support nerve health just as good nutrition does not simply support the health of one particular body part. Most supplements that have shown some benefit for DPN have also shown some benefit for healthy circulation. The poor health that damages your nerves can also damage circulation to your feet and legs. A supplement that may support a healthy blood sugar level may also be an antioxidant, and support circulation health. A supplement that may support healthy circulation may also support nerve health. Many of the supplements that support nerve and circulation health have strong anti-inflammatory and antioxidant properties. Diabetes and prediabetes metabolic syndrome are accompanied by chronic inflammation and harmful “oxidative stress.” Oxidative stress is what creates the harmful “free radicals” that most readers have probably heard about. Inflammation and oxidative stress are believed to be at the root of much of the disease caused by these medical problems. Your nerves, blood circulation, and blood sugar levels may be supported by the same supplement. Supplements do not work like pharmacy prescription drugs that proclaim to work on a single problem (the other actions they have are called sideeffects). Nerve health supported through proper nutrition and diet supplementation (for some) can have real practical benefits because of the often painful symptoms that come about as a result of diseased nerves found in patients with diabetic nerve damage. For more information in this area, including the use of food, movement, smart nutritional supplementation and lifestyle for the prediabetic, I also write and serve as the chief-editor at Nutrientology. I hope this report informs and motivates you toward not only helping yourself, but helping and encouraging others. I have included links to Pure Encapsulation products sold at the Nutrientology Store because I know they are of a high and trusted quality. I have confidence in recommending them, but there are other sources of high quality products from which to choose. If you need help locating these sources, speak to your podiatrist. You may also email me – I would be happy to help. I do not have a direct financial interest in the Nutrientology Store, but I have personally verified the Pure Encapsulations supplement products as my wife Kimberly is the president of Nutrientology LLC. Please feel free to pass this report on to a friend that may benefit from this information. Motivate your friends and family members to make some basic changes toward better health. Speak to your doctor for assistance and guidance in making these positive changes. Legal: Statements made, or any products sold through this report, or at Store.Nutrientology.com, are not intended to diagnose, treat, cure, or prevent any disease. Consult a qualified health care practitioner who is aware of functional dietary supplementation before taking any substance for medicinal purposes. The Pure Encapsulation products available at Store.Nutrientology.com are to be used for the supplemental dietary management of your health. It is advised that these products be used under medical supervision as part of your on-going medical health management. The supplements available at Store.Nutrientology.com are not intended for use by children under the age of twelve, by pregnant or lactating women, or people taking prescribed “blood thinners.” Nutrientology LLC will assume no responsibility for any adverse event or unpleasant experience you may incur as a result of this report. The resources listed in this report are not necessarily fully systematic or complete, nor does any inclusion here imply any endorsement or recommendation to you for your particular problem by Robert Creighton or Nutrientology LLC. Robert Creighton and Nutrientology LLC make no warranties, express or implied, about the value or utility, for any purpose, of the information and resources contained in this report. *** Section 1 Diabetic Peripheral Neuropathy This medical condition is the result of increased and irregular blood sugar levels damaging your nervous system. This "short-circuiting" of the nerve signal in the feet and legs causes altered sensations that will often be painful. Patients will often tell me, “My feet are numb, but they hurt.” The nerve endings in the feet give the brain a “shortcircuited” message that can be experienced as shooting pain, numbness, burning, tingling, decreased coordination and reflexes, as well as muscle weakness. And as if the pain and numbness is not enough, poor nerve health can also result in skin, muscle, and even bone and joint changes. Problems with nerves and circulation in the feet and legs of diabetics - and even some pre-diabetics - cause most of the problems faced in this vulnerable part of the body. The foundation of preventing and managing the harmful “side-effects” of diabetes is the control and stabilization of your blood sugar levels. This is accomplished through a proper lower carbohydrate diet, regular movement, and a healthy lifestyle. The exact connection between blood sugar control and the development and severity of DPN is not fully understood. I will often see type 2 diabetics that appear to have good blood sugar readings, but will have classic neuropathy signs and symptoms. There is more to it than your blood sugar level, but that doesn’t mean you should not maintain healthy blood sugars. A proper diet and adequate daily exercise as well as adequate sleep are very important parts of maintaining healthy blood sugar levels. Neuropathy can often be diagnosed through clinical exam. The difficulty in some cases can be in determining the cause of the problem. If the patient is diabetic, this is the likely cause, but that doesn’t mean there may not be other causes of your nerve pain and/or numbness. I often see diabetics who have symptoms of nerve damage in their feet from spine surgery. Another example would be a diabetic patient who has a vitamin B12 deficiency. There are other problems that can contribute to neuropathy in the feet and legs. There are nerve electrical tests, blood tests, different imaging scans, and rarely nerve biopsy available to determine what may be causing nerve damage in the feet and legs. Treatments for Diabetic Peripheral Neuropathy Treating diabetic and pre-diabetic neuropathy is difficult. Doctors are usually left with managing the poor blood sugar control that is believed to contribute to the nerve damage along with trying to stop the symptoms. Some of you may be familiar with the prescription drugs that are available to manage the symptoms of DPN including: tramadol/Ultram, hydrocodone/Vicodin, oxycodone/Percocet, amitryptyline/Elavil, carbamazepine/Tegretol, gabapentin/Neurontin, pregabalin/Lyrica, and duloxetine/Cymbalta. From what I have seen, pregabalin and gabapentin appear to be the most commonly prescribed, and have the lowest frequency of side effects among the oral medicines. Unfortunately there is currently no magic pill that will cure DPN. People have also used acupuncture, TENS, spinal cord stimulation, massage therapy and even surgery. There are also various topical products that have been used: Neurogen is available over the counter along with capsaicin-containing products made from a derivative of hot peppers. Specially mixed formulations of prescription drugs are also available that can be applied to the skin. One such formula contains: ketoprofen (anti-inflammatory), amitriptyline (anti-neuropathy), gabapentin (anti-neuropathy), and lidocaine (anesthetic). Despite the various pharmacy treatment options that are available, the prescription treatment of chronic painful diabetic nerve damage remains a challenge. The sideeffects of the oral medications can also limit their use. Often some combination of approaches needs to be used for the management of this difficult problem. The best option would be to combine treatments that address both the causes and the symptoms of this difficult problem. The problem is, we do not know the exact cause, and there are different forms of neuropathy in different diabetic and pre-diabetic patients. The management of your diabetic nerve damage does not have to be with either a prescription medicine or a supplement. You can use both as “combination therapy.” There are several diet supplements that can be considered as a legitimate part of combination therapy. There is increasing research indicating that non-prescription diet supplements - “nutrient medicines” - may offer some benefit to patients afflicted with DPN. Before we delve into the supplements section of this report, I need to state the obvious one more time - Healthy blood sugar levels and the promotion of nerve health starts with a healthy diabetes or prediabetes diet and exercise-movement lifestyle. It is preferable that you obtain proper nutrients from the food you eat. Any supplement or medication is not to be thought of as a panacea or a replacement for doing what is necessary to improve your overall health through eating proper food, moving, and living a healthy lifestyle. This report also includes the foods that are high in the nutrients that have been shown to be supportive of nerve health in the face of diabetes and prediabetes metabolic syndrome. Do not ignore the power of food…food is medicine. And just like there is no prescription magic pill for the difficult problem of diabetic nerve damage, there is no magic diet supplement either. You need to take an “all of the above” approach if you really want to get better…just being honest with you. A discussion about what makes up a proper diabetes or prediabetes diet is beyond the scope of this report –it is a complex subject, and can be different for different people. I have compiled some basic foundational information about food and movement for people with pre-diabetes in my eBook, “STOP Prediabetes: Eat S.A.F.E. and Don’t Be a Sea Squirt” as well as in the many posts and other resources at Nutrientology.com. You can get a copy of the e-book by signing up for Nutrientology News here. Read on and become more informed…knowledge is power. *** Section 2 Nutrients and Supplements for Diabetic Peripheral Neuropathy In this section I am going to review each of the diet supplements that have shown some scientific promise in assisting with diabetic neuropathy. Several vitamins and supplements have been shown to play some positive role in helping DPN. This report discusses the more well-researched diet supplement options for supporting the management of this difficult problem. In the following pages I am going to inform you about these nutrients and supplements that have shown some supportive role toward: Healthy blood sugar levels - the foundation of nerve health. Healthy nerves to alleviate direct nerve damage and its symptoms. Healthy blood circulation to the nerves to indirectly support relief of diabetic neuropathy. You should not take high doses of any supplement mentioned in this report - or elsewhere - no matter how beneficial it is reported to be. Just like with pharmacy medicines, you can take too much of a vitamin or other nutrient and negative sideeffects can and will develop. I know most of you didn’t sign on to this report for all this academic research science stuff, so if you want to skip this information and get right down to the nitty-gritty regarding what I would recommend, you may jump ahead to Section 3. If you do skip ahead, I would encourage you to come back and take a look at this information at some point in the future. It really is interesting, and it’s usually a good idea to have some understanding about why you are doing something. You may be more likely to stick with a healthy lifestyle if you know the rationale behind what you are doing…make sense? *** The top 5 supplements for diabetic neuropathy are: Acetyl-L-carnitine Alpha-lipoic acid Benfotiamine B12 (with or without Folate and B6) Biotin (with or without Chromium) *I have also included 5 additional Bonus Supplements* 1. Acetyl-L-Carnitine Acetyl-L-Carnitine (ALC) is a powerful antioxidant that is a special form of L-carnitine. ALC is only available as a supplement while L-carnitine is found naturally in your body. It is involved in the burning of fats and in the production of energy. L-carnitine is made in your liver and kidneys with the help of vitamin C. Research has shown that ALC has a pain killing effect. Taking an ALC supplement has been shown to: support the health of nerves benefit in the management of nerve pain protect nerves support growth factors in nerve cells support the regeneration of peripheral nerves in animal studies 2,3 Peripheral nerves are the nerves outside of the brain and spinal cord and include the nerves to the feet and legs. It is this ability to support peripheral nerves and reduce nerve pain that makes acetyl-L-carnitine a point of medical interest for diabetic neuropathy. Research One aspect of ALC’s ability to help protect nerves is through its role as a strong antioxidant. One study looked at the benefit of three strong antioxidants and their ability to support nerve health in the face of an experimental toxin exposure to nerve cells. The antioxidants used in the study were ALC, Alpha Lipoic Acid (another one of the top 5) and Vitamin C. Researchers saw reduced pain signals caused by the nerve toxin coming from nerve cells that were also exposed to these three supplement antioxidants.4 Researchers have advised that ALC be recommended to patients early in the nerve damage process to provide the best benefit before the neuropathy gets too bad. 5 One of the questions I ask diabetic patients is if they are feeling any numbness or tingling in their feet. Many will say, “yes every once in a while.” This is the patient in which good blood sugar control through a healthy diabetes diet, exercise, lifestyle change and diet supplementation may prevent worsening of diabetic neuropathy symptoms and in some people may very well also reduce the need for diabetes medication. ALC research has also demonstrated its support for autonomic neuropathy. 6 Autonomic neuropathy causes damage to the nerves that control things you do not have any conscious control over such as the constriction and dilation of blood vessels that regulate the blood flow and body temperature of your skin. Acetyl-L-Carnitine was well tolerated in a human study that lasted over a year.7 Foods Sources: ALC is a special form of L-carnitine that is only available as a supplement. L-carnitine is found in meats with red meat and pork being a high source, and poultry and fish containing less. Dairy products also contain reasonable amounts. Supplement Sources: Acetyl-L-Carnitine *** 2. Alpha Lipoic Acid Alpha lipoic acid (ALA) is found naturally in the body. It has many interesting properties including being a powerful antioxidant and anti-inflammatory. High blood sugar levels are associated with excess generation of highly reactive free radicals and oxidative stress.10 ALA promotes antioxidant effects in the body mostly by directly eliminating harmful free radicals. It also appears to play a role in blood sugar levels as well as having an apparent beneficial effect on managing the symptoms of diabetic neuropathy. 8 In light of this, it has been suggested that some of ALA’s potential as a supplement for DPN goes beyond its actions as an antioxidant. 11 ALA appears to target and influence cellular signaling pathways which increase blood sugar uptake and the use of sugar by the cells of your body. It therefore appears to benefit DPN in two ways: indirectly through insulin and blood sugar effects, and directly through an apparent action on the damaged nerves themselves.12 Another apparent indirect benefit of ALA is through the health of the small blood vessels that supply the nerves. Although it’s not yet clear, it appears ALA may offer some benefit through its effects on the lining of blood vessels known as the endothelium - I will write more about the blood vessel lining known as the endothelium when I discuss vitamin B12. Alpha lipoic acid has been used as a therapy for diabetic neuropathy in Germany for over 30 years.9 Research There have been a number of studies looking at the ability of alpha lipoic acid to reduce the symptoms of diabetic neuropathy. One study showed that intravenous ALA treatment improved the ability of the endothelium to open up blood vessels and improve blood flow in patients with type 2 diabetes.13 Other research noted an improvement in neuropathy symptoms, but no increase in blood flow to the skin. 14 Researchers have also looked at the effect of intravenous use of ALA at 600 mg once daily for three weeks. Results suggested that alpha lipoic acid helped to bring about a significant and clinically relevant reduction in neuropathy pain, and the researchers confidently recommended its use for control of neuropathy symptoms.1 The use of alpha-lipoic acid over three months helped to decrease the symptoms of diabetic neuropathy - There was subjective improvement after ALA use in all but one case out of the 100 patients who were part of the study.60 In another study comparing ALA to a placebo the authors concluded, “Oral ALA may improve neuropathic symptoms in diabetic distal symmetrical polyneuropathy.”16 Even though our bodies naturally make lipoic acid with an enzyme called lipoic acid synthase (LASY), research suggests that LASY is often deficient in type 2 diabetics leading to an overall disturbance in the body’s antioxidant defenses, increased inflammation, insulin resistance, and mitochondrial dysfunction.17 The mitochondria are often referred to as the power plants of the cells of your body. Although ALA has many potential applications for health, it is important to be aware that in rare cases its use apparently triggered an insulin autoimmune syndrome. East Asians and some North American natives that have a certain genetic predisposition to this syndrome are particularly susceptible, and the vast majority of the literature on this topic is from Japan.61,62 Nevertheless, if you feel like you may be having feelings of low blood sugar while taking ALA, you should stop taking it, and tell your doctor. In the very rare cases in which this occurred, once the ALA was stopped, the problem went away. No supplement, or medication for that matter, will help everyone, but alpha lipoic acid has shown promise. The use of ALA is a well established therapeutic approach for both the prevention and management of diabetic neuropathy. Foods Sources: ALA is found in red meat, organ meats (liver), and yeast, particularly brewer's yeast. Supplement Sources: Alpha Lipoic Acid GlucoFunction - An Alpha Lipoic Acid containing supplement with other nutrients for nerve and blood sugar support. *** 3. Benfotiamine Benfotiamine is a dietary supplement that is derived from vitamin B1, known as thiamine. Benfotiamine quickly converts to high levels of an active form of thiamine. The primary benefit of this supplement for diabetics with nerve damage in the feet and legs is due to its strong "anti-AGE" properties. “AGEs” are Advanced Glycosylation End products that form as a result of excess sugar in the blood. Excess blood sugar will “stick on and in” nerves, blood vessels, and many other vital structures in your body causing AGEs. In the feet and legs this can potentially result in nerve pain and other diabetic complications because the nerves can’t work well with sugar “stuck on them.” The anti-AGE effect of benfotiamine makes it potentially helpful not only for the management of diabetic nerve damage, but also for diabetic kidney disease and diabetic eye disease. Some recent studies have also shown additional non-AGErelated benefits of benfotiamine.18 One of these benefits is its support of glucose sugar use by the body, as well as influencing the passage of nerve signals.19 Because of these properties, as well as its strong anti-AGE effect, benfotiamine can be a treatment option for patients with diabetic polyneuropathy.20 Research The ability of benfotiamine to reduce AGEs has been shown in several studies. In a small trial involving type one diabetics, benfotiamine plus alpha lipoic acid showed a strong ability of these supplements to reduce the accumulation of harmful AGEs. 21 Another study looked at the benefit of benfotiamine as an AGE fighter in people with rheumatoid arthritis (RA). Like diabetes, RA involves chronic inflammation and is associated with poor function of the delicate cells that line blood vessels. The poor function of these cells – known as endothelial cells - is instigated by the inflammation caused by AGEs “attacking” these cells. The study looked at the function of endothelial cells in people with rheumatoid arthritis who were given a supplement containing benfotiamine 50 mg + pyridoxamine (B6) 50 mg + methylcobalamin (B12) 500 μg. Researchers found that people taking the supplements had reduced advanced glycation end products, improved endothelial function and less inflammatory disease activity.22 I write about pyridoxamine (B6) and methylcobalamin (B12) later in this report (they are also members of the top 5). Many other studies have supported the role of benfotiamine to reduce the damage of advanced glycation end products and to support neurovascular health.23,24,25 Benfotiamine has the ability to suppress three major pathways that affect sugar’s damaging impact on your nerves and circulation, especially the small blood vessel circulation in your eyes, kidneys, and feet. More research is needed, but many believe this is the reason why it may be clinically useful in preventing the development and progression of complications associated with diabetes,26 and by extension pre-diabetes. Given that Benfotiamine has shown some promising benefit as a supplement for relieving symptoms of diabetic neuropathy, researchers have tried to figure out what the best dose would be. It appears that benfotiamine is most effective in larger doses, although even in smaller daily doses, either in combination with other supplements, or by itself, it is effective.27 An example of benfotiamine combination therapy was mentioned above in the rheumatoid arthritis study. You will recall this study used Benfotiamine + B6 (pyridoxamine) + B12 (methylcobalamin). There is actually another study that looked at the effectiveness of diabetic neuropathy treatment with a combination of Benfotiamine + B6 + B12. The authors of this study concluded that, “the benfotiamine + vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy.” 28 The other combination supplement therapy I mentioned above is benfotiamine + alpha lipoic acid (another combination of two top 5 DPN supplements). If you are unable to do the combination therapy you should consider starting simply with benfotiamine and see how you do after 60-90 days. If you are not noting any changes in the uncomfortable sensations in your feet and legs, you can then add either vitamin B12 by itself, or the B12, B6, and Folate (B9) combination that I write about below, as well as alpha lipoic acid or a any of the top diabetic neuropathy supplements found in the RivitalAge group. In light of the evolving understanding of the importance and multiple benefits of making sure your thiamine levels are appropriate, one medical researcher said, “even mild thiamine deficiency in diabetes should be avoided and thiamine supplementation…should be considered as adjunct nutritional therapy to prevent…the development of vascular complications in clinical diabetes”29 - “vascular complications” refers to the damage and decrease in healthy blood circulation that often occurs in diabetic patients. Foods Sources: Benfotiamine is not found in food. But most foods contain small amounts of thiamine. Larger amounts of thiamine can be found in pork and organ meats. Other good dietary sources include whole-grain or enriched cereals and rice, legumes, wheat germ, bran and brewer's yeast. However diabetics and prediabetics should steer clear of cereals. Supplement Sources: Neuremedy is a benfotiamine supplement that is often available in many podiatrists’ offices. Benfotiamine can be found in some supplement stores. *** 4. Vitamin B12 (methylcobalamin or cyanocobalamin) with or without Vitamin B6 and Folate The most common form of vitamin B12 is cyanocobalamin. This is the form of B12 found in most multivitamins, and it is also used for vitamin B12 fortification of certain foods, cereal for example. Although, if you have diabetes you should not be eating cereal. Methylcobalamin is another form of vitamin B12. It is the active form of vitamin B12 found in better DPN supplements. Vitamin B12's main functions are in the formation of red blood cells and DNA that make up your genes. It is involved in having a healthy nervous system, and plays a vital role in the metabolism of healthy fats essential for maintenance of the important covering that surrounds your nerves known as the myelin sheath. In the diabetic, B12 is typically used to assist in the management of diabetic neuropathy, and for general nerve health. The main property of vitamin B12 that has been studied for DPN is its role in managing homocysteine levels - Elevated levels of homocysteine in the blood have been associated with poor circulation, and it is believed that the decreased circulation in the tiny blood vessels that feed the nerves are part of the problem in people with DPN. There are actually three B vitamins that play a role in the metabolism and breakdown of homocysteine – Vitamin B12, B6, and B9 (Folate) – I will write about each of these in this report. These three B vitamins are believed to be helpful for DPN by keeping homocysteine levels from rising, and as a result supporting the health of the tiny blood vessels that carry oxygen and nutrients to your nerves. Homocysteine is interesting. It often comes up in association with a number of medical problems, but exactly how it fits into the puzzle is not clear. An elevated homocysteine level is considered to be a marker of poor health of the blood vessels through which your circulation flows. Increased homocysteine in the bloodstream has been shown to be a predictor of blood circulation problems.33 Remember that I wrote about the endothelium in the section on benfotiamine - that thin delicate layer of endothelial cells that line your blood vessels? When these cells are not happy your circulation suffers. Although many researchers believe increased homocysteine is a contributing cause to the decreased circulation that is part of cardiovascular disease, we are not sure whether increased homocysteine is a cause or a result of cardiovascular disease. Studies have looked at the association between homocysteine and blood vessel circulation damage along with combinations of B vitamin supplements to reduce the worsening of the damage commonly referred to as “hardening of the arteries. 30, 31 Risk factors for elevated homocysteine levels in the blood include: elderly male alcohol use smoking diabetes kidney disease certain medications32 Vitamin B12 diet supplementation becomes a strong consideration in people with diabetes whether they have diabetic peripheral neuropathy or not. Low vitamin B12 levels are common among people both with and without diabetes. Low vitamin B12 levels have been labeled the most common nutritional deficiency in the developing world, and possibly in the United States; this is especially true for vegans, and the elderly.34 Diabetics can also be susceptible to vitamin B12 insufficiency because many diabetics take the drug metformin to help control their blood sugar levels. Metformin is a good medication, and you should not stop taking it, but it has been shown that long term treatment with metformin increases the risk of vitamin B12 deficiency which can result in raised homocysteine levels.35 Several studies have looked at the prevalence of Vitamin B12 deficiency in people taking metformin over a long period of time, especially the elderly. In one study, long term metformin use resulted in vitamin B12 deficiency in 30% of patients. 36 Another study found that vitamin B 12 deficiency was present in 22% of a group of primary care type 2 diabetic patients.37 Medical researchers believe that strong consideration be given to regular measurement of vitamin B12 levels during long term metformin treatment. 38 The good news is that it has been shown that simply adding an oral methylcobalamin supplement corrected Vitamin B12 deficiency in almost 50% of patients with low vitamin B12 levels. 36 Research A review of studies looking at the effect of a vitamin B12 supplement on the symptoms of peripheral diabetic neuropathy suggests that even though objective nerve testing may not show much change, the symptoms patient’s experience may be decreased nevertheless.39 More studies are needed to confirm the effects of vitamin B12 on diabetic neuropathy. That includes both B12 by itself as well as B12 combined with B6 and Folate. If vitamin B12 combination therapy is recommended, it should include folate or methyfolate, and not folic acid - more about this popular combination later in this special report. By the way, as I mentioned near the beginning of this report, taking a prescription medicine for diabetic peripheral neuropathy doesn’t prevent you from also using a supplement. With a difficult problem like DPN, you need to address it from many angles, including a proper lower-carbohydrate diet and exercise. Speak to your doctor about “how to eat.” Foods Sources: Eggs, meat, milk and milk products, poultry, shellfish and various foods fortified with vitamin B12 Supplements Sources: Vitamin B12 can be used as a single supplement either as cyanocobalamin - or preferably methylcobalamin. It is often combined with vitamin B6 and Folate (B9). There is a special formulation of B vitamins that have shown some promise in assisting in the management of DPN. This supplement formula includes 3 “activated” B vitamins: 1. Methylcobalamin- the active form vitamin B12 2. Pyridoxal-5-phosphate-the active form of vitamin B6 3. L-methylfolate- the active form of folate (B9). It is called Homocysteine Factors. Pure Encapsulations Homocysteine Factors contains these three active B vitamins to support nerve health by way of nerve blood flow through the management of homocysteine levels in the blood. It also contains trimethylglycine (betaine) and vitamin C - two of the bonus DPN supplements that I discuss below. Methylcobalamin – vitamin B12 Homocysteine Factors - contains the active forms of vitamins B12, B6 and folate along with trimethylglycine (betaine) and vitamin C - two of the bonus DPN supplements that I discuss below. Ultra B Complex with PQQ - an excellent Pure Encapsulations B Complex Product for DPN (in addition to PQQ, it also contains thiamine, inositol and alpha lipoic acid!) RevitalAge Nerve - Another more complete multiple supplement product with vitamins B12, B6, Folate and vitamin C along with acetyl-l-carnitine, alpha lipoic acid, Coenzyme Q10 and magnesium. Vitamin B6 (pyridoxine or pyridoxal-5-Phosphate) Like many of the other B vitamins, vitamin B6 comes in different forms. Pyridoxal-5phosphate is the active form. It is involved in many areas of your metabolism, from the formation of hemoglobin that carries oxygen in your blood, to the working of your genes, to the release of stored-up glucose in your muscles, and many other important actions including the formation of the biologic chemicals that nerves use to “talk to one another.” And like vitamin B12 it is also involved in the formation of the covering for your nerves the myelin sheath I told you about. This is one way in which vitamin B6 directly supports nerve health. In addition - as you learned in the section on Vitamin B12 - it is also involved in the management of homocysteine in your body. It therefore also indirectly promotes nerve health by supporting healthy nerve circulation. As you also know from the discussion of vitamin B12, the accumulation of homocysteine is suspect in the development of diabetic nerve damage because of its association with the ill-health of the tiny blood vessels that supply the nerves to the feet and legs. Low vitamin B6 has been linked to an increased risk of cardiovascular diseases, and research suggests that it may have some role in supporting healthy circulation beside its effect on homocysteine metabolism. This benefit was suggested by a study that looked at the effect of Vitamin B6 in a large group of older adults in Puerto Rico in which low vitamin B6 concentrations were associated with inflammation, higher oxidative stress, and a poor metabolism.40 Vitamin B6 may also have an anti-AGE benefit through its derivative, known as pyridoxamine. You will remember that I talked about “anti-AGE” at length in the section on Benfotiamine. Research using an animal model suggests that pyridoxamine may slow the decrease in blood vessel elasticity that can occur in diabetics over time as a result of AGE formation. The decrease in blood vessel elasticity as we age puts extra stress on our heart because it has to pump blood into a blood vessel that has a harder wall with less “give.” Research has shown that vitamin B6 appears to inhibit the formation of advanced glycation end products and their damaging effect on the large main blood vessel called the aorta.41 Vitamin B6 insufficiency is more common than many realize with the elderly and smokers especially susceptible.42 Food Sources: Many meats including poultry and fish, beef liver, milk, cheese, beans, spinach, carrots, many whole grains, and sunflower seeds. Supplement Sources: Homocysteine Factors - contains the active forms of vitamins B12, B6 and folate along with trimethylglycine (betaine) and vitamin C - two of the bonus DPN supplements that I discuss below. Ultra B Complex with PQQ - an excellent Pure Encapsulations B Complex Product for DPN (in addition to PQQ, it also contains thiamine, inositol and alpha lipoic acid!) RevitalAge Nerve - Another more complete multiple supplement product with vitamins B12, B6, Folate and vitamin C along with acetyl-l-carnitine, alpha lipoic acid, Coenzyme Q10 and magnesium. Folate (L-methylfolate) Folate, yet another B vitamin (B9), is also essential to many of your body’s functions. The human body needs folate to make, repair, and regulate DNA, to develop red blood cells, to support good nervous system function, and to act as a cofactor in many of the biological reactions that keep you healthy. Folate participates in the breakdown of fat in fat cells and may have some role in the prevention of obesity and type 2 diabetes. Many people know that diabetes is a disease of blood sugar control, but many do not know that it is also a disease of fat storage. Any dietary nutrient that plays a supportive role in proper fat metabolism needs to be a regular part of the diabetes and pre-diabetes diet. Once eaten folate must chemically change to become the activated, functional Lmethylfolate. The better supplements for DPN contain L-methylfolate so the active form of folate is being directly delivered to your system without having to go through the conversion process. Like vitamin B6 and vitamin B12, folate is involved in the regulation of homocysteine – as I discussed earlier, increased homocysteine levels appear to be somehow associated with cardiovascular disease. Study results tend to support the belief that elevated homocysteine has a role in the development of “hardening of the arteries” by promoting the blockage process of both small and large blood vessels in diabetic patients.43,44 Research I have only discussed the uncomfortable, if not downright painful, symptoms of diabetic neuropathy thus far; however another aspect of this problem that can put the diabetic patient at risk is the development of skin ulcerations due to the lack of feeling in the feet that can come about as a result of DPN. One study looked at the association of diabetic ulceration of the foot and homocysteine levels in the blood. Researchers looked at 198 type 2 diabetic patients in order to see if there was a relationship between homocysteine (among other things) and diabetic foot ulceration. They found that homocysteine was significantly higher in patients with foot ulceration, along with protein in the urine, and increased HbA1c. This does not mean that increased homocysteine caused the ulcers or that you can heal an ulcer by decreasing your homocysteine level - There are many factors at work. Regardless, you should manage your health proactively, and do what you can do now to prevent diabetic complications in the future. The authors of this study concluded that as homocysteine levels increased, diabetic foot ulceration also increased. They encouraged more research looking at the association of homocysteine levels with the risk of foot ulceration.45 Another study also suggested an association between leg ulcers and elevated homocysteine levels. The authors of this study advised reducing homocysteine in the early stages when skin changes first start to develop.46 The association of folate, homocysteine and circulation health in the feet and legs is far from clear. Scientists studying folate and folic acid are coming up with mixed results, ranging from folic acid improving the function of the cells that work on growth and repair of blood vessels in patients with type 1 diabetes47 to low levels of folate being only weakly associated with thickening (“hardening”) of arteries in the neck that supply the brain.48 The effect of homocysteine levels on healthy blood circulation needs more medical research. Folate vs. Folic Acid Another area that needs more investigation is the difference between folate versus folic acid in the diet and as a supplement. Folic acid supplementation has been a source of controversy. Notice that I said folic acid not folate. Folic acid is typically considered to be the common supplement form of folate, but there is an important difference between these two different forms of vitamin B9. Folic acid is actually a synthetic form of folate – it is not found naturally. It is a synthetic compound that is used in many diet supplements and in the vitamin fortification of food because it is inexpensive and easy to make. The terms “folate” and “folic acid” are often used interchangeably in the nutrition and vitamin literature, but they are not the same thing. Folates are members of the B vitamin family and are present naturally in foods such as green leafy vegetables. These natural folates are metabolized in the lining of the small intestine, but it appears folic acid undergoes its initial metabolism in the liver by an enzyme that is believed to have low activity in humans resulting in unnatural and possibly harmful levels of unmetabolized folic acid in the body when too much is ingested. 49 The effect of combining Vitamin B12 with either folic acid or folate on homocyteine levels has been done in people with kidney disease with varying results. I can’t help but wonder if at least part of the difference in the results of these studies lies in the use of folic acid in one of the studies and folate in the other. One study used oral folate with a vitamin B12 (methylcobalamin) supplement. This combination was given intravenously to patients on kidney dialysis. The patients receiving these supplements saw their increased homocysteine levels return to normal and showed less “hardening of the arteries.” The authors suggest that this regimen may have greater potential than folate alone to decrease cardiovascular risk in patients with renal failure.50 Another study looked at short-term oral folic acid supplementation with or without vitamin B12 (methylcobalamin) in diabetics without kidney disease, and found that it also appeared to be an effective approach to decrease homocysteine levels. 51 On the other hand, researchers looking at the effect of combination B-vitamin therapy (folic acid, vitamin B6, and vitamin B12), and its ability to lower levels of homocysteine in people with pre-existing kidney disease, found a greater increase in “vascular events” (heart attack, stroke, and the need for circulation surgery in the legs) and a greater decrease in kidney function.52 Could unmetabolized folic acid be harmful to poorly functioning kidneys? So, by now I assume you are thoroughly confused. Part of the reason for this is that folic acid and folate are often used interchangeably in the health literature. See this example from a recent article on folic acid food fortification in Europe. The difference between folate and folic acid supplements may not make a difference for a healthy individual, but why not err on what appears to be the safe side? Obtain folate from food. If you do not eat adequate amounts of folate containing foods, consider a folate containing supplement rather than a folic acid containing one (although folic acid supplements have shown benefits for the developing child of pregnant women). When looking for B complex supplements containing folate look for products that list “5methyltetrahydrofolate” or “5-MTHF” on the label or that contain the Metfolin brand of folate. Check your multivitamin, most contain folic acid and not folate - More incentive to eat better, i.e. real food, not food made with a machine and having a label. Foods Sources: Folate is found in green leafy vegetables, asparagus, broccoli, cauliflower, beets, and lentils. Not surprisingly, some of the best food sources of folate are calf’s liver and chicken liver. Supplement Sources: Homocysteine Factors - contains the active forms of vitamins B12, B6 and folate along with trimethylglycine (betaine) and vitamin C - two of the bonus DPN supplements that I discuss below. Ultra B Complex with PQQ - an excellent Pure Encapsulations B Complex Product for DPN (in addition to PQQ, it also contains thiamine, inositol and alpha lipoic acid!) RevitalAge Nerve - Another more complete multiple supplement product with vitamins B12, B6, Folate and vitamin C along with acetyl-l-carnitine, alpha lipoic acid, Coenzyme Q10 and magnesium. *** 5. Biotin (and Chromium) I have included these two nutrients together because much of the diabetes and diabetic neuropathy research has done so. Chromium and biotin play important roles in regulating carbohydrate metabolism.53 Biotin is another B vitamin (vitamin B7) that has shown some benefit for diabetes. It is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids. Diabetics may benefit from its use as a diet supplement as there is some evidence that a combination of biotin and chromium support healthy blood sugar levels in people with diabetes.54 There is also some evidence, albeit sparse, that biotin can reduce the pain of diabetes nerve damage by reducing both the numbness and tingling associated with DPN.55 Chromium is an essential trace mineral that plays a role in the metabolism of glucose and in supporting healthy blood sugar levels in people with diabetes. It benefits nerve health in diabetes and pre-diabetes through this well-known ability to support healthy blood sugar levels. Research Studies suggest that both biotin and chromium positively support healthy blood sugar levels. Biotin appears to maintain insulin output from the pancreas promoting healthy glucose tolerance. Likewise chromium picolinate has been shown to support insulin sensitivity, and healthy blood sugar levels in some diabetics.56 Research on type 2 diabetics suggests that a chromium supplement alone or combination chromium, vitamin C and vitamin E was effective for reducing oxidative stress and improving glucose metabolism in type 2 diabetic patients.57 I included vitamin C below as a bonus supplement to support nerve health and healthy blood sugar levels. Preclinical studies have shown that the combination of chromium picolinate and biotin significantly enhances both glucose uptake in muscle cells and the “burning” of glucose for energy. A pilot study demonstrated that supplementing with a combination of chromium picolinate and biotin in poorly controlled diabetics receiving anti-diabetic medication improved glucose management and several lipid (blood fat) measurements.58 The chromium and biotin combination is interesting. As one group of medical researchers put it, “Affordable, safe, and convenient, chromium picolinate plus biotin …could prove to be a cost-effective complement to existing prescription therapies for controlling type 2 diabetes.”63 Foods Sources: Food sources of chromium include brewer's yeast, meats (including organ meats), cheeses, whole-grain products. Biotin can be found in brewer's yeast, egg yolk, sardines, nuts, beans, whole grain products and mushrooms. Supplement Sources: Chromium (picolinate) 200 mcg. GlucoFunction – a blend of vitamins and supplements to support healthy blood sugar levels. In addition to chromium and biotin, it also contains other top diabetic neuropathy supplements including magnesium and vitamin C. *** 5 Bonus Supplements that may support nerve health and healthy blood sugar levels 1. Trimethylglycine (Betaine) or Choline Trimethylglycine (TMG) - also called betaine – along with choline, are two more “homocysteine fighters.” Both are found naturally in the body and betaine can be made from choline. They are both part of the pathway that breaks down homocysteine. As you now know, this pathway also includes vitamin B12, B6 and Folate. TMG has been known to play some beneficial role for the heart since the 1950s. It was first called betaine because it was discovered in sugar beets. It has been approved by the US Food and Drug Administration for use as a supplement to treat a genetic condition where too much homocysteine builds up in the body. Biological molecules that come from choline serve as important parts of membranes. Choline is also the source of acetylcholine, a chemical compound that nerves use to talk to one another as well as how to signal your muscles to move. Because choline reduces the blood levels of homocysteine, like vitamins B6, B12, and folate, it may also assist in heart and circulation health. Choline is obtained from the food you eat, and it can also be made in your body. Choline and betaine levels have shown some association with metabolic syndrome, and it has been suggested that a disruption of the normal process of choline changing into betaine in the small “energy factories” in your cells, known as mitochondria, is part of the error in metabolism found in pre-diabetes or metabolic syndrome.64 Betaine insufficiency is not only associated with metabolic syndrome, but also lipid disorders, diabetes, and it may have a role in other diseases.67 Betaine supplementation has been shown to decrease total homocysteine levels in humans. 68,69,70 Although one of the cited studies only showed this in people with low vitamin B12 and folate levels. 70 Isn’t it something how these vitamins and supplements always seem to come up together? Despite the fact that your body can make some choline, it was officially recognized as an essential nutrient by the Institute of Medicine in 1998. Different people require different amounts of choline depending on their genetics, so you may have more or less of a dietary requirement for choline than your neighbor. Because choline is involved in many critical functions in your body, and given that many people do not obtain enough choline, it is wise to eat foods rich in choline.65 Postmenopausal women have a higher dietary requirement for choline than do premenopausal women.66 In light of the fact that these compounds are involved in homocysteine metabolism, a diet rich in betaine or choline might benefit cardiovascular health through its homocysteine-lowering effects with resultant improved circulation to the nerves. Hopefully future research will improve our understanding of the relationship between homocysteine, blood circulation and nerve health. Unlike vitamin B12, betaine and choline do not play any direct role in nerve health. Foods Sources: Food sources of betaine include beets, broccoli, grains, shellfish, and spinach. Supplement Sources: VitaEssentials – a multi-vitamin containing choline and inositol for nerve health (this multi-vitamin contains a lower B vitamin dose) 2. Vitamin C Vitamin C, known chemically as ascorbic acid, is an essential nutrient. It acts as an anti-oxidant, meaning that it protects the body against so-called “oxidative stress.” It does this by acting as a “reducing agent” to reverse the often damaging oxidation processes that produce “free radicals.” I know, too many quote signs, but I am assuming that most of you have not taken biochemistry…just go with me on this one. When there are more harmful free radicals (reactive oxygen species) in the human body than there are antioxidants to counter them, a condition called “oxidative stress” develops. Vitamin C has an impact on various medical conditions that are especially relevant to diabetics and prediabetics including cardiovascular disease, high blood pressure, chronic inflammation, and blood sugar control. The most often published benefit of vitamin C is as an anti-oxidant, and that goes for its benefits in the health of the diabetic and pre-diabetic patient as well. Diabetics can be especially prone to decreased levels of vitamin C and typically have lower vitamin C levels than non-diabetics.78 Decreased vitamin C levels appear to cause poor health of the lining of blood vessels that I have written about called the endothelium. 79 A small study of young patients with type 1 diabetes, showed an association between lower vitamin C levels and negative changes in: the circulation of the smallest blood vessels (those supplying the nerves for example) the arteries of the legs the electrical function of the heart80 Other research has looked into the idea that daily vitamin C can improve the blood tests of diabetics due to its antioxidant capacity and apparent ability to support kidney and liver health.81 One study looked at the effect of an antioxidant “vitamin C cocktail” containing vitamin C, pomegranate extract, and green tea extract. It was shown to work against the negative effects of oxidative stress and the formation of free radicals in patients with type 2 diabetes, and the authors believed this approach might be beneficial in preventing cardiovascular complications.82 In addition to its benefit as an antioxidant, vitamin C also appears to play some positive role in healthy blood sugar levels. A study looked at blood sugar control in a group of people with high blood pressure suggesting that poor anti-oxidation ability is influencing poor blood sugar control.83 More recent research (2011) examined the effect of giving seventy type 2 diabetics vitamin C along with their metformin for three months. The researchers looked at the relationship between fasting blood sugar levels (FBS), blood sugar levels after eating (PMBG), glycosylated hemoglobin (HbA1c), and the level of vitamin C. The diabetics in this experiment were divided randomly into a placebo and a vitamin C group of 35 each. They had all had decreased levels of vitamin C, but this was reversed significantly in the group that was given vitamin C along with their metformin, compared to the group who took their metformin without vitamin C. All the measures of blood sugar levels also showed significant improvement after 12 weeks of treatment with vitamin C. The authors of the study concluded, “Supplementation of vitamin C with metformin reverses ascorbic acid levels, reduces FBS, PMBG, and improves HbA1c. Hence, both the drugs in combination may be used in the treatment of type 2 DM to maintain good glycemic control.”84 Foods Sources: All fruits and vegetables contain some amount of vitamin C. Foods that are the highest sources of vitamin C include: Cantaloupe Citrus fruits Kiwi fruit Mango Papaya Pineapple Berries Watermelon Vegetables that are the highest sources of vitamin C include: Broccoli, Brussels sprouts, cauliflower Green and red peppers Spinach, cabbage, turnip greens, and other leafy greens Sweet and white potatoes Tomatoes Winter squash Supplement Sources: Ascorbic Acid (Vitamin C) 1,000 mg. capsules Buffered Ascorbic Acid (vitamin C) 1,000 mg. Capsules GlucoFunction *** 3. Magnesium (and Calcium) Magnesium and calcium are important minerals that play many essential roles in your health. They are both important for good nerve function. Most people are generally aware of the need for calcium in the diet largely because of the public health information regarding osteoporosis prevention in post-menopausal women and the commercial marketing efforts of the dairy industry. Magnesium doesn’t get as much press, but it should. It is hugely important. Calcium and magnesium are “sister nutrients,” but unfortunately it seems magnesium is the ignored ugly stepsister when it is actually the Cinderella of minerals. Surveys taken in the U.S. over 30 years indicate a rising calcium-to-magnesium food-intake ratio among adults and the elderly, excluding intake from supplements, and supplements also favor calcium over magnesium.85 Perhaps calcium has stolen the spotlight because, given its prevalence in bones, it is such a tangible mineral that people can identify with. It is therefore easier to market, i.e., sell. Nevertheless, it is advised that your daily intake of magnesium should actually be more than that of calcium.86 Magnesium is commonly reported to be a cofactor in over 300 health promoting reactions in your body. It plays a role in proper muscle and nerve function, heart rhythm, immune system, strong bones, blood sugar levels, blood pressure, metabolism and making proteins. Low magnesium intakes and blood levels have been associated with type 2 diabetes, pre-diabetes/metabolic syndrome, increased inflammation, increased blood pressure, “hardening of the arteries” and blockage of blood circulation, sudden heart stoppage, and weakened bones, among other things. One study found that almost half (48%) of the US population consumed less than the required amount of magnesium from food in 2005-2006, but the number was decreased from 56% in 2001-2002.85 It is magnesium’s role in the diabetic that is most relevant to this special report. Research suggests that having sufficient magnesium improves the areas of health that are of particular importance to people with diabetes and pre-diabetes: poor glucose control, inflammation, and oxidative stress.87 Lower intakes of magnesium and lower magnesium levels in the blood are associated with metabolic syndrome, insulin resistance, and type 2 diabetes,88 and there is increasing evidence that irregular magnesium metabolism is part of a possible underlying connection between insulin resistance, high blood pressure and a decreased ability to manage blood sugar. 89 In addition to unhealthy blood sugar levels, low magnesium has been associated with heart problems, high blood pressure, diabetic eye disease, kidney problems, nerve disease, and foot ulcerations. Because magnesium has been associated with so many problems in diabetics, medical researchers have advocated routinely monitoring its levels in diabetic patients and treating low levels whenever possible.90 Low magnesium has been reported to be more common in people with type 2 diabetes compared to non-diabetics (Remember the same for vitamin C?) Studies have shown that decreased magnesium occurs at an incidence of 13.5% to 47.7% in people with type 2 diabetes with many contributing causes for this insufficiency. The benefits of magnesium supplementation has been shown to improve the health of blood vessels, blood pressure, heart function, and many other areas of health.91 Calcium is the most abundant mineral in the body. Calcium assists in many functions including muscle contraction, healthy blood vessel widening and narrowing to control blood flow, release of hormones, and transmitting signals throughout your nervous system, among many other things. Although it plays a number of important roles, less than 1% of total body calcium needs to be available to support these functions. The other 99% of the body's calcium is found in the bones and teeth where it provides structural support. The balance between bone being broken down and built-up changes with age, and when blood calcium levels drop too low, calcium is "borrowed" from the bones, and it is deposited back to the bones from calcium supplied through the food you eat…assuming you are eating food that has enough calcium in it. Calcium deficiency is usually due to an inadequate intake of calcium. If your diet is low in calcium, there may not be enough calcium available in the blood to be returned to the bones to maintain their strength, and overall total body health. The average person loses 400 to 500 mg of calcium per day. It is found in some foods, added to some foods, and available as a dietary supplement. Food Sources: Rich sources of magnesium include green leafy vegetables and nuts - Brazil nuts, almonds, cashews, pine nuts, pistachio nuts and black walnuts. Legumes, whole grains, bananas, chocolate, and cocoa powder. Supplement Sources: RevitalAge Nerve - Another more complete multiple supplement product with vitamins B12, B6, Folate and C along with acetyl-l-carnitine, alpha lipoic acid, Coenzyme Q10 and magnesium. *** 4. L-Taurine Taurine is an amino acid that is found throughout your body in very small amounts. It has several known functions, including acting as an antioxidant, and influencing the chemical messengers that transmit nerve signals. Taurine is produced by methionine and vitamin B6 (B6 shows up again). Homocysteine breakdown involves its conversion to methionine. As I am sure you have realized by now, many of the vitamins and supplements in this report are interconnected. There is evidence that taurine may have a beneficial effect in preventing diabetesassociated small blood vessel and kidney disease as well as playing some role in insulin sensitivity. Taurine is also a sulfonyl derivative like the prescription sulfonylurea anti-diabetes medicines. Taurine and insulin both have mutual stimulating actions with hypoglycemic properties.71,72 Supplementation with taurine has been found to be beneficial in counteracting oxidative stress and in preventing experimental diabetic nerve, kidney, and eye damage; Recent research using animal models suggests that taurine may have blood sugar lowering effect and have some benefit for the insulin resistance of diabetes and its complications, including diseases of the nerves, eyes, kidneys, blood circulation and heart muscle.73 Taurine’s antioxidant properties have been shown to positively support nerve blood flow, the speed at which the nerve impulse travels, and how sensitive nerves are in feeling sensations using experimental type 2 diabetes in animals with nerve damage.74 Because of its influence on nerves, if taurine levels become low in people with diabetes this may contribute to increased nerve excitability and the pain of peripheral diabetic neuropathy.75 Taurine is considered to be a conditionally essential nutrient in that although your body can usually make enough to meet basic needs, people with certain medical problems, such as cardiovascular disease and diabetes, may not have adequate taurine levels. Under these circumstances, taurine basically becomes a necessary nutrient like a vitamin.76 (You will recall that I told you about choline also being an essential nutrient even though your body can make it.) Also, last but not least, taurine has also been shown to “antagonize” homocysteine levels and sufficient taurine intake might be an effective way of reducing cardiovascular diseases, such as the blockage of blood vessels known as atherosclerosis. 77 So, in addition to its direct role in nerve health through its influence on nerve chemicals, this may be another way in which taurine may support healthy normal nerve function. Foods Sources: Taurine is especially prevalent in seafood and meat. Supplement Sources: Taurine *** 5. L-Arginine Like the previously discussed L-taurine, L-arginine is also an amino acid nutrient. Like many of the other nutrient supplements discussed in this special report, the benefits and functions observed with L-arginine that are most relevant to this report are based on its positive effect on blood circulation, including the circulation in the very small blood vessels that supply your nerves. L-arginine acts as a building block for an important molecule called nitric oxide. Nitric oxide is essential for: blood vessel relaxation the maintenance of blood pressure glucose blood sugar uptake. Like many of the other nutrients I have talked about in this special report, L-arginine treatment has been shown to improve endothelial health, inflammation, and insulin sensitivity in people with type 2 diabetes.92,93 Low levels of L-arginine in the blood leads to decreased nitric oxide levels. Nitric oxide has many positive effects on blood flow. It reduces blood vessel stiffness, increases blood flow, and improves the function of your blood vessels by its effect on the thin lining of your blood vessels known as the endothelium (yes, that word again…are you getting the feeling it is important?). If levels of nitric oxide are decreased, insulin resistance and high blood pressure will result.94 The cells of your endothelium need to be healthy for them to properly benefit from nitric oxide. The poor endothelial health often found in diabetics is a major factor in the development of the poor blood circulation associated with diabetes. High blood sugar levels are damaging to the endothelium, and L-arginine has been suggested as a possible nutritional therapy for improving diabetic circulation disease.95 Nitric oxide regulates insulin function and release, transmission of nerve signals, and the immune system. Recent studies have shown that endothelial cells making reduced amounts of nitric oxide from L-arginine is a major factor contributing to the impaired action of insulin in the circulation system of obese and diabetic people – the medical name for this impaired action is called vascular insulin resistance.96 The cells lining your blood vessels – the endothelium - make more nitric oxide when you exercise. This naturally promotes blood flow, and it has been suggested that this is one way in which exercise seems to promote improvements in health.94 Arginine is considered a semi-essential amino acid because even though the body normally makes enough of it, supplementation is still sometimes needed…remember the concept of a “conditionally essential nutrient” that I wrote about earlier in this report when I referred to choline and taurine? Although the question regarding the safety of taking L-arginine immediately after a heart attack is far from settled, it is good advice to avoid this supplement immediately after a heart attack.97 Food Sources: Good food sources of arginine are very similar to those of magnesium. Given that arginine is an amino acid, protein foods are one place to look. Meats and nuts, along with garlic and onions have very high levels of arginine. Supplement Sources: L-Arginine can be found as an isolated supplement in the vitamin aisles or at a reputable company online. *** Section 4 So, Where Do You Start? I know I have given you a lot of information, and much of it may have been too scientific for your liking, so I’ll get right down to the practical advice I can give you based on the current medical science. First and foremost you need to speak to qualified health professionals about the proper diet, exercise and lifestyle for you. There are no “magic pills.” Having said that, if you are having symptoms of diabetic neuropathy, and you want to consider supplementing healthy food, I would recommend: RevitalAge Nerve because it is a complete product containing the top known vitamins and supplements to support relief of diabetic neuropathy in the feet.* If you would rather proceed more slowly with a step-wise approach, I would advise the following: Start with a simple vitamin B12 supplement. If you can get the B12 supplement as methylcobalamin that would be the best, but cyanocobalamin is okay. A B-complex supplement can be considered, instead of just the B12 by itself. I would recommend one with Folate and not Folic Acid. Homocysteine Factors can be considered in this case. Or Ultra B Complex with PQQ You can then consider adding another B vitamin derivative known as Benfotiamine although this may be difficult to find in the local nutrition stores. If you are not noting any change in 90 days - and you are eating healthy food - decrease the dose to one B vitamin supplement every other day, or every third day, and add… Alpha Lipoic Acid daily for 90 days. If some better reduce to every other day. Alpha lipoic acid by itself or even better… GlucoFunction – a complex of vitamins and supplements to support healthy nerves and blood sugar levels. In addition to alpha lipoic acid, chromium and biotin, it also contains other top diabetic neuropathy supplements including magnesium and vitamin C.* If not any better, reduce to every other day and consider adding Acetyl-LCarnitine. Acetyl-l-carnitne After 90 days, you can generally reduce the dosage and frequency of a dietary supplement. Any insufficiency or deficiency that you may have had should be better, and you do not want to take something that the body no longer needs on a daily basis. You will also be eating better food during this time, moving about more and generally becoming healthier. Your body will still need good nutrients, but likely in lower dosages because of your healthier life. *These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease. To the best of my knowledge none of the statements made throughout this report have been evaluated by the FDA, and all products are not intended to diagnose, treat, cure or prevent disease. *** I hope this special report is helpful to you. I wish you all the best. REFERENCES 1. National Heart Lung and Blood Institute. What is Metabolic Syndrome. www.nhlbi.nih.gov/health/health-topics/topics/ms/ 2. Di Cesare Mannelli L, Ghelardini C, Toscano A, et al. The neuropathy-protective agent acetyl-L-carnitine activates protein kinase C-gamma and MAPKs in a rat model of neuropathic pain. Neuroscience. 2010 Feb 17;165(4):1345-52. 3. Vanotti A, Osio M, Mailland E, et al. Overview on pathophysiology and newer approaches to treatment of peripheral neuropathies. CNS Drugs. 2007;21 Supplement 1:3-12; discussion 45-46. 4. Joseph EK, Chen X, Bogen O, Levine JD. Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy. Journal of Pain: Official Journal of the American Pain Society. 2008 May;9(5):463-72. 5. Evans JD, Jacobs TF, Evans EW. Role of acetyl-L-carnitine in the treatment of diabetic peripheral neuropathy. The Annals of Pharmacotherapy. 2008 Nov;42(11):1686-91. 6. Gorio A, Di Giulio AM, Tenconi B, et al. Peptide alterations in autonomic diabetic neuropathy prevented by acetyl-L-carnitine. International Journal of Clinical Pharmacology Research. 1992;12(5-6):225-30. 7. De Grandis D, Minardi C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. 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