There are many dietary supplement strategies that can be used to support and promote your weight loss efforts in the gym and while you're dieting. Some of these strategies are old, and some are more recent; but rarely can you find a dietary supplement ingredient that approaches the issue of weight loss from an entirely new angle. Consequently, it's been very interesting for me to research and write about blueberry leaf extract.

Glucose And Fat Storage
To understand the contribution that Blueberry leaf can make to weight loss, we must first discuss the role of glucose (blood sugar) in relation to weight gain. First of all, glucose is obtained from sugars and other carbohydrates in our diet. All carbohydrates (except for fiber) are generally converted into glucose in our livers.¹ The glucose is then used as a fuel in energy metabolism to help power our bodies. But what happens if our energy needs are already met; what does our body do with the glucose? Basically, a healthy body has two choices: it can convert a limited amount of it into glycogen (muscle sugar), and it can convert unlimited amounts of it into body fat which can be stored for an extended period of time.² As a matter of fact, a small protein in liver cells is largely dedicated to helping convert excess dietary carbohydrates into fat stores.³

So, besides the obvious avoidance of excessive carbohydrates and sugar-laden foods, what can be done to inhibit this process of converting carbs into fat? There are three strategies, which can be used:

• Reduce glucose absorption from the diet,
• Reduce glucose synthesis in the liver,
• Accelerate glucose metabolism.

Ideally, the most effective strategy would be to achieve all three at the same time.

Chlorogenic and Hydroxycinnamic Acids
Recent research has identified two unique natural compounds that appear to do just that. The two compounds are: chlorogenic and hydroxycinnamic acids. New studies suggest that taken together these two unique compounds:

• May help to reduce dietary glucose absorption in the intestines,
• Help reduce glucose synthesis in the liver, and
• Speed up the metabolism of glucose—simultaneously.

Here's how it works: The enzyme glucose-6-phosphatase (G6P) plays a major role in the formation of glucose in our body. Chlorogenic acid was recently discovered to specifically inhibit the activity of this key enzyme. Inhibition of G6P activity in the liver results in a reduction of liver glucose production—which in turn may help reduce high rates of glucose output by the liver.^4,5

In fact, both chlorogenic acid and hydroxycinnamic acid (aka, caffeic acid) are involved in the glucose reduction in our body. Research of Dr. Welsch and his colleges at Rutgers University reveals that glucose absorption in the intestines was reduced to 80 percent in the presence of chlorogenic acid and 30–40 percent in the presence of caffeic acid. These results suggest that both chlorogenic and caffeic acids are involved in the regulation of glucose level including the unique ability to inhibit dietary glucose absorption in intestines.⁶ Other recent research also indicates that the presence of caffeic acid accelerated the metabolism of glucose, which can reduce the total glucose concentration in circulating blood.⁷ Results of other studies provide further evidence that caffeic acid is involved in the reduction of blood glucose in diabetic animals.⁸

Pharmaceutical companies also actively interested in this important area of research have already synthesized several synthetic analogs of chlorogenic acid. These compounds are potent inhibitors of the glucose-6- phosphatase activity in the human liver.⁹ Other evidence has also confirmed that chlorogenic acid derivatives reduce blood glucose in animals, which also confirms the blood glucose lowering properties of chlorogenic acid.^10,11

Therefore, it is strongly suggested from all the above that the effectiveness of chlorogenic and caffeic in glucose reduction will depend on whether these compounds are taken simultaneously and in sufficient amounts.

Blueberry Leaves

So, what does all this have to do with Blueberry leaves? Surprisingly enough, concentrations of chlorogenic and caffeic acids have recently been discovered in the Blueberry leaves (Vaccinium arctostaphylos L) found in the Caucasian Mountains of the northern region in the Republic of Georgia (in the previous Soviet Union). Interestingly, Caucasians have been using medicinal teas infused with leaves of the blueberry for the self-treatment of diabetes for literally centuries. In light of the previous information about chlorogenic and caffeic acids and their effect on blood glucose levels, this folk use of Blueberry leaves for diabetes makes sense.

Caucasian blueberry has a legendary reputation as aid to diabetics. Decoctions and infusions of the leaves are used in folk medicine as hypoglycemic agents and are usual major component of "anti-diabetes teas." Even more impressive, in Russia, a standardized blueberry leaf extract, known as "Diabetic Chai Cherniki" was effectively used for the treatment of diabetes, gastric colitis and high cholesterol, and has been repeatedly shown to contain pharmaceutically significant levels of both chlorogenic and caffeic acids.¹²

Now back to the concept of using Blueberry leaves extract as a strategy for weight loss. The logic is fairly simple: if you can reduce the amount of glucose that is absorbed, reduce the amount that is manufactured in the liver, and increase the rate at which glucose is metabolized, the result is that you'll likely be able to reduce the conversion of glucose into body fat. Of course, this does not mean that Blueberry leaves extract is a license to eat as much sugary and carbohydrate-rich foods as you'd like, but rather that if you're making an effort to eat a healthy, balanced diet, that Blueberry leaves extract can help prevent the carbohydrates that you are consuming into being converted to body fat. A good dose of blueberry extract is 200 mg.

References:

1. Whitney E, Cataldo C, Rolfes S. Understanding Normal and Clinical Nutrition, Fifth Edition (1998) West/Wadsworth, Belmont, California. pp. 114.
2. Whitney E, Cataldo C, Rolfes S. Understanding Normal and Clinical Nutrition, Fifth Edition (1998) West/Wadsworth, Belmont, California. pp. 116–8.
3. Yamashita H, et al. Proceedings of the National Academy of Sciences USA 2001;98:9116.
4. Arion WJ, et al. Arch Biochem Biophys (1997) 15; 339(2):315–22.
5. Hemmele H, et al. J Med Chem (1997) 17; 40(2):137–45.
6. Welsch, et al. J Nutr (1989) 119(11):1698–704.
7. Cheng JT, Liu IM. Naunyn Schmiedebergs Arch Pharmacol (2000) 362 (2):122–7.
8. Hsu FL, Chen YC, Cheng JT. Planta Med (2000) 66(3): 228–30.
9. Simon, et al. Arch Biochem Biophys (2000) 15; 373(2):410–28.
10. Herling, et al. Eur J Pharmacol (1999) 386(1):75–82.
11. Mshavanadze VV. Bulletin of the Georgian Academy of Science (1971a) 62:189–92.
12. Mshavanadze VV. Bulletin of the Georgian Academy of Science (1971b) 62:446–7.

For over 40 years the conventional medical establishment has been telling us that high cholesterol levels are the main cause of heart disease. However, many scientific studies have shown that this is not the case.

• A Massachusetts Institute of Technology study examined the scientific literature on cholesterol and could not find one study with a clear cause and effect relationship between cholesterol and heart disease. Many similar studies have now confirmed this fact.
• Dr. Stephen Sinatra published a book entitled The Cholesterol Myth in which he recounts the original research on cholesterol over 50 years ago when 45 out of 50 studies could not find a clear connection between cholesterol as the cause of heart disease.
• Dr. Mark Hyman reviewed the literature on the effectiveness of statin drugs, the number one cholesterol medication, and determined that 150 people would need to take the drug before one person would live longer than they would have without taking the drug.

Yes, statin drugs do lower cholesterol, but it is very clear that they do not save many lives. And, this would seem to answer the question in the title of this article, that people still experience heart attacks even if they have perfect cholesterol. In fact, 50 percent of people who experience a heart attack have perfect cholesterol levels. So, if cholesterol is not the cause of heart disease, what is? There are several factors, but probably the main one is the presence of inflammation in the body. Inflammation can be caused by many factors including the following:

• Nutrition- eating eggs, dairy, animal protein, sugar, processed foods and non-organic foods.
• Toxins- chemicals in the air, water and food that we consume.
• Genetics- some people make fewer enzymes than needed, make too much cholesterol in their livers or have weaknesses in their arteries.
• Exercise- many people do not get enough exercise, which is needed to help arteries expand and contract.
• Stress- many people are overstressed, which causes the body to make cortisol, a hormone that can damage our arteries.
• Poor diet- beyond the bad foods mentioned above, many people simply do not eat enough nutritious food and are deficient in vitamin B, vitamin C, vitamin D, vitamin E, Omega 3 fats, magnesium and many other nutrients that are important for the heart and cardiovascular system.

Many of these causes contribute to the development of inflammation in the body due to the oxidative process. When we consume or are exposed to unhealthy foods, toxins, stress or acidic foods, free radicals are created. These molecules have a missing electron, which steals an electron from one of our healthy cells. This creates a pothole in our arteries that must be repaired as soon as possible. The patching material is made in the liver and it is called, you guessed it, cholesterol. So, cholesterol is at the scene of the so-called crime, performing a very important function. Cholesterol also helps to make vitamin D3 and many other biochemicals. Lowering cholesterol too much can actually cause serious health issues in many parts of the body. This patching process could be completely avoided if people consumed enough antioxidants that can give back the missing electron that is often needed. And, where are these antioxidants found? They are in the more nutritious foods such as fruits, vegetables, nuts and seeds with high levels of vitamin C, vitamin E, selenium, zinc, and astaxanthin.

Based on this initial assessment on the cause of heart disease here are some beginning strategies.

• Eat a diet, such as the Mediterranean Diet, with an emphasis on vegetables, fruits, nuts, and seeds.
• Exercise at least 45 minutes every day with aerobic, strength and flexing included.
• Manage stress with avoidance, meditation, yoga, music, deep breathing, etc.
• Do not drink tap water due to the presence of fluoride and chlorine.
• Take nutritional supplements to optimize key nutrient levels such as vitamin C, vitamin D, magnesium, vitamin B, and Co-Enzyme Q10. These, and other, heart-friendly nutrients are deficient in the diets of a majority of people in the United States.
• And, if you want to take control of your personal health, and reduce the risk of ever having a heart attack, make sure you get the right tests to determine if you are beginning to move in that direction.

Most people get their blood tested as part of the health insurance program provided by their employer.

Others, who are not employed must arrange for tests on their own through Medicare or via personal health insurance plans. In any case, these tests are not usually adequate because of cost restrictions, or doctors who are not aware of the best blood tests to utilize. Here is an explanation of these blood test alternatives.

Tests usually provided in common situations:

• Cholesterol- usually total cholesterol, LDL cholesterol and HDL cholesterol
• Glucose- either total glucose or A1C glucose (fasting level)
• Insulin- total insulin (fasting level) • Triglycerides- total triglycerides

Tests often added by personal request from the patient, or a progressive doctor:

• Hormones- either the male or the female panel
• C-reactive protein- measures the level of inflammation in the body
• Homocysteine- measures the level of vitamin B6, vitamin B12 and folate (methylators)
• Cortisol- measures the level of stress in the body
• RBC magnesium- this test is superior than current magnesium tests
• Glucose tolerance- this test can identify cellular sugar challenges five to seven years earlier

Tests rarely provided due to high cost and lack of awareness of their importance:

• INR- measures the thickness of the blood and thus the likelihood of clots forming
• Omega 3- measures the level of this healthy fat in the body
• CoQ10- measures this enzyme important for energy production and providing the DNA in our cells
• Heavy metals- measures the level of these dangerous toxins in the body
• Apolipoprotein B- measures the level of this early warning protein before LDL increases
• Galectin 3- measures Galectin levels which is an early warning marker for heart disease and cancer
• TMAO- trimethylamine N-oxide is a bacteria produced compound that measures the amount of choline in the body, which is known to contribute to the production of blood clots and plaque.

Many people might look at these tests and say why should I pay hundreds of dollars to get all of these tests? The answer could be that you probably only need to have these tests done every three to five years, depending on your age and health status. The more important reason would be that these tests could provide an early warning system, five to ten years earlier, for the future development of heart disease. By getting these tests every three to five years, and following the lifestyle guidelines previously mentioned, there is a high probability that you will never experience a heart attack or a stroke in your long and healthy lifetime.

When people read an article like this many will ask questions such as, “don’t I get all of the nutrients I need from the food I eat” or “can I take one pill to get all of the nutrients that are not in my food?” The answer to both questions is NO! It is virtually impossible to get all of the nutrients we need from food alone. In a study by the National Cancer Institute of over 16,000 people aged 2 to 80, the researchers could not find one person with a truly healthy diet. In fact, vast majorities were deficient in 11 out of 14 nutritional categories. They were not eating enough vegetables, fruits, healthy fats, nuts, and seeds. This is due to declining nutrients in the soil, over processing of foods, poor selection by shoppers, overcooking, poor chewing and compromised digestive systems. People are simply not getting the nutrients they need to sustain the healthy functioning of their cells. That is one of the main reasons why the number of adults with a chronic illness has increased from 10 percent over 60 years ago to nearly 70 percent today. When cells do not get the nutrients they need they go through a gradual deterioration process in five stages, as shown on the following page.

The recommended blood tests can identify changes in the body’s chemistry at the stressed and weakened stages of cellular deterioration, five to ten years before more serious problems develop.

A strategy to prevent and even reverse heart disease
Some people are very interested in avoiding heart disease, stroke, and other cardiovascular illnesses. They eat what they think is a healthy diet; they exercise as much as they feel is necessary; they avoid stress; they take nutritional supplements, and they get their blood tested every year. These are all good lifestyle decisions, as far as they go. However, as we have seen in this article these steps may not be sufficient to prevent heart disease or some other chronic illness. The blood tests that have been recommended can help to provide an early warning mechanism for anyone, which can then be augmented with nonbiochemical tests such as thermography, MRI for the carotid artery evaluation, and even a CT scan if it is deemed necessary. (Excess radiation exposure should be factored in.)

Nutritional superstars for the heart and cardiovascular system.
Conventional medicine will tell you that there is no science to support the use of nutritional supplements to improve your heart and circulation system. They even have a web site that repeats these erroneous messages on a regular basis. However, this is absolutely not true and there are thousands of clinical studies to prove that nutritional supplements help to prevent chronic illness and often reverse it. Some good sources for these studies are Life Extension Magazine, GreenMedInfo, Metagenics, and books entitled “The Encyclopedia of Natural Medicine” and “The Prescription for Nutritional Healing.” There are over 40,000 scientific studies that prove nutritional supplements work very well, but the pharmaceutical industry does not want you to know that. Here are the top ten nutrients you should look into to protect your body from heart disease.

1. Co-enzyme Q10- protects our cellular nucleus and improves energy production in mitochondria.
2. Magnesium- is the transport agent for all glucose and insulin into the cell, to make energy.
3. Vitamin C- is the key antioxidant for reducing free radicals that cause damage to our arteries.
4. Vitamin D- regulates calcium levels, which impacts how nerves carry messages to the heart.
5. Resveratrol- protects blood vessel walls and promotes healthy levels of LDL and HDL.
6. Garlic- controls blood pressure, encourages blood vessels to stay open and slows plaque build-up.
7. Pycnogenol- helps thin the blood and control levels of dangerous choline in the body.
8. Omega 3 oils- reduces apolipoprotein B, triglycerides, and VLDL, all heart challengers.
9. Vitamin B- niacin (B3) lowers LDL and triglycerides; increases HDL and improves circulation. Vitamin B6, B12 and folate lower homocysteine levels (inflammation).
10. Modified citrus pectin- reduces heavy metals, lowers cholesterol, removes plaque and helps keep Galectin 3 levels in balance. Also, lowers PSA levels. Prevents cancer and kills cancer cells.

These nutrients perform many other useful functions to help keep our bodies healthy. CoQ10 helped reverse kidney disease in one study. Magnesium helps to prevent and reverse type 2 diabetes. Vitamin C treats many cancers effectively. Vitamin D3 reduces the risk of breast cancer by 77 percent and prostate cancer by 83 percent. These are truly the superstars of nutritional supplements. There are many other effective nutrients for heart health, and there is excellent science behind each and every one of them. This is merely a snapshot of what is possible in terms of improving someone’s ability to develop an evidence-based strategy for optimum heart health. Now you can complete this journey to better health by researching the recommendations presented here and working with your health care providers to find the best future strategy for you.

About sixty to seventy percent of all people with diabetes have some form of nerve damage, called neuropathy (or more accurately, neuropathies, since there is more than one kind). High blood sugar levels over a long period of time damages nerves throughout the body, but those in the hands and feet are most often damaged. Symptoms of diabetic neuropathy can include pain and numbness, particularly in the hands and feet, or problems with digestion, the urinary tract, blood vessels, and the heart. These symptoms can range between mild and extremely painful to the point of disability.¹ This article will review some information on diabetic neuropathies (DNs), then take a look at specific dietary supplements that may help in the treatment of this problem.

The Types Of Diabetic Neuropathies

According to the National Institutes of Health², DNs are most common in those who have problems controlling their blood glucose levels, those with high blood lipid levels (i.e., cholesterol and triglycerides), those with high blood pressure and those who are overweight.

Other factors can also contribute to the cause. The risk increases with age and with the length of time a person has diabetes. Those who have had diabetes for at least 25 years have the highest rates of neuropathy.

There are different types of DNs, with their own symptoms:³

• Peripheral neuropathy is the most common type of DN. It causes pain or loss of feeling in the toes, feet, legs, hands, and arms.
• Changes in digestion, bowel and bladder function, sexual response, and perspiration take place in autonomic neuropathy; the nerves that serve the heart and control blood pressure, as well as nerves in the lungs and eyes, may be affected as well. Hypoglycemia unawareness, a condition in which people no longer experience the warning symptoms of low blood glucose levels, may also occur.
• Proximal neuropathy results in thigh, hip, or buttocks pain, and leads to weakness in the legs.
• Sudden weakness of one nerve or a group of nerves, causing muscle weakness or pain, is caused by focal neuropathy. In this case, any nerve in the body can be affected.

DIETARY SUPPLEMENTS

There are a number of dietary supplements with the potential to help in the treatment of DN. Some of the most promising are acetyl-L-carnitine, alpha lipoic acid, benfotiamin, gamma-linolenic acid and methylcobalamin.

Acetyl-L-Carnitine
Acetyl-L-carnitine (ALC) is a form of the amino acid L-carnitine. Both have similar roles in helping to transport fat into muscle cells where it can be burned for energy. Also, the “acetyl” part of ALC helps produce the acetylcholine, a brain chemical, which is required for various mental functions. ALC occurs naturally in the brain, liver and kidneys.

ALC has been shown to be deficient in diabetics.⁴ In double-blind research, type 1 or type 2 diabetics with peripheral neuropathy experienced improved symptoms after taking 1500–3000 mg ALC daily in divided doses for a year. ALC seems to increase nerve fibers, regenerate clusters of nerve fibers, and improve sensations. In patients who have pain as the most significant symptoms, taking ALC 1000 mg two to three times daily also decreases neuropathy-related pain within six months of beginning treatment. Lower doses (500 mg three times daily) do not seem to reduce pain. ALC also seems more likely to be effective for reducing pain in patients with a shorter duration of diabetes and patients with poorly-controlled type 2 diabetes.^5,6,7,8 In research, the best response was associated with using 1,000 mg ALC, three times daily.

Orally, acetyl-L-carnitine is generally well tolerated. One gram daily of L-carnitine seems to significantly increase the anticoagulant effects of acenocoumarol.^9,10 Acenocoumarol is an oral anticoagulant similar to warfarin, but shorter-acting. This interaction has only been reported with L-carnitine, but theoretically could occur with acetyl-L-carnitine.

Alpha Lipoic Acid
Alpha lipoic acid (ALA) is a natural antioxidant manufactured by the body and similar to certain vitamins. Unlike most other antioxidants, however, it has the advantage of being soluble in both fat and water, so it can provide production both inside and outside of cells.¹¹ ALA is also found in some foods, particularly liver and yeast.

Giving 600 mg to 1200 mg oral or intravenous ALA daily reduced symptoms of peripheral neuropathy in diabetics. ALA improved symptoms such as burning, pain, numbness, and prickling of the feet and legs. It also seems to improve objective measures such as ratings of nerve function decline and disability. Symptom improvement occurs within three to five weeks with oral and intravenous dosing.^{12,13,14,15,16,17,18,19,20} Doses lower than 600 mg daily have not been shown to be effective.²¹ Furthermore, other research shows that ALA can also contribute to reducing blood sugar levels and insulin sensitivity.^22,23,24,25 A daily dosage range of 600 mg to 1200 mg ALA is likely to yield positive results.

Skin rash has been reported in some individuals after using oral doses of alpha-lipoic acid.²⁶ Theoretically, use with other hypoglycemic drugs might cause additive blood sugar lowering effects.²⁷

Benfotiamin
Benfotiamin is a particularly well-absorbed form of vitamin B1. Double-blind research in diabetics demonstrated that oral doses of 400 mg daily resulted in a statistically significant improvement in neuropathy score in the treatment group compared to placebo. The most significant improvement reported was pain decrease in polyneuropathy (a type of peripheral neuropathy).²⁸ Other research has demonstrated statistically significant effectiveness in reducing diabetic neuropathy pain with daily doses ranging between 150–320 mg benfotiamin.²⁹ In addition, studies have also shown that benfotiamin in combination with other B vitamins is effective in the treatment of DNs.³⁰ Best results will probably be seen with 400 mg of benfotiamin daily.

Benfotiamin has a good tolerance profile without any adverse effects, and no established drug interactions.

Gamma Linolenic Acid
Gamma linolenic acid (GLA) is an omega-6 fatty acid commonly found in evening primrose oil (derived from the seeds of the evening primrose plant) as well as black currant seed oil and borage oil. The body converts GLA into an anti-inflammatory, hormone-like substance called prostaglandin E1. In addition to DN, GLA has shown benefit in the treatment of eczema³¹, fibrocystic breast disease³², premenstrual syndrome³³ and rheumatoid arthritis.³⁴

In double-blind research, taking oral doses of 360 to 480 mg GLA daily for six months to one year reduced symptoms and prevents nerve deterioration in peripheral neuropathy patients who have type 1 or type 2 diabetes.^35,36,37,38 It seems to be more effective in patients with better glucose control compared to patients with poor glucose control.³⁹ Take 360 to 480 mg GLA daily. It may take six months or longer for results.

Orally, gamma-linolenic acid (GLA) can cause mild gastrointestinal effects such as nausea, vomiting, soft stools, diarrhea, flatulence, and belching.^40,41,42 GLA might prolong bleeding time.⁴³ GLA appears to have anticoagulant effects.⁴⁴ Theoretically, taking GLA with other anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.

Methylcobalamin
Methylcobalamin is a well-absorbed form of vitamin B12. In double-blind research, daily oral supplementation of 1500 mcg methylcobalamin by diabetics resulted in significant improvements in autonomic neuropathy compared to placebo.⁴⁵ Other research also demonstrated similar benefits and improvements in autonomic neuropathy when methylcobalamin was given orally or as an injection.^46,47

Orally and intramuscularly, vitamin B12 does not usually cause adverse effects, even in large doses. Limited case reports suggest that chloramphenicol (an antimicrobial drug) can delay or interrupt the response of immature red blood cells to supplemental vitamin B12 in some patients.⁴⁸ A daily dose of 1500 mcg methylcobalamin is appropriate.

Conclusion
Just in case you’re wondering, you can use any or all of these dietary supplements indicated at the same time. Other than the adverse reactions listed, there are none associated with the concurrent use of more than one supplement.

1. Diabetic Neuropathies: The Nerve Damage of Diabetes. NIH Publication No. 08–3185. Bethesda, MD: National Diabetes Information Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. February 2008. Retrieved October 3, 2008 from http://diabetes.niddk.nih.gov/dm/pubs/neuropathies/
2. Ibid. Diabetic Neuropathies.
3. Ibid. Diabetic Neuropathies.
4. Sima AAF, Calvani M, Mehra M, et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: An analysis of two randomized, placebo-controlled trials. Diabetes Care 2005;28:89–94.
5. Onofrj M, Fulgente T, Melchionda D, et al. L-acetylcarnitine as a new therapeutic approach for peripheral neuropathies with pain. Int J Clin Pharmacol Res 1995;15:9–15.
6. De Grandis D, Minardi C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D 2002;3:223-31.
7. Quatraro A, Roca P, Donzella C, et al. Acetyl-L-carnitine for symptomatic diabetic neuropathy. Diabetologia 1995;38:123.
8. Sima op. cit.
9. Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.
10. Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385.
11. Kagan V, Khan S, Swanson C, et al. Antioxidant action of thioctic acid and dihydrolipoic acid. Free Radic Biol Med 1990;9S:15.
12. Ziegler D, Hanefeld M, Ruhnau K, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A 7-month, multicenter, randomized, controlled trial (ALADIN III Study). Diabetes Care 1999;22:1296–301.
13. Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alphalipoic acid): A 2-year, multicenter, randomized, double-blind, placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res1999;31:171–7.
14. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid: A 3-week, multicenter, randomized, controlled trial (ALADIN Study). Diabetologia 1995;38:1425–33. 15. Ruhnau KJ, Meissner HP, Finn JR, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med 1999;16:1040–3.
15. Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid. Diabetes Care2003;26:770-6.
16. Ziegler D, Nowak H, Kemplert P, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A meta-analysis. Diabet Med 2004;21:114–21.
17. Negrisanu G, Rosu M, Bolte B, Lefter D, Dabelea D. Effects of 3-month treatment with the antioxidant alpha-lipoic acid in diabetic peripheral neuropathy. Rom J Intern Med 1999;37:297–306.
18. Zeigler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care 1997;20:369–373.
19. Tankova T, Cherninkova S, Koev D. Treatment for diabetic mononeuropathy with alpha-lipoic acid. Int J Clin Pract 2005;59:645–650.
20. Sachse G, Willms B. Efficacy of thioctic acid in the therapy of peripheral diabetic neuropathy. Hormone Metab Res Suppl 1980;9:105–7.
21. Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with Type 2 diabetes. Diabetes Care 1999;22:280–7.
22. Jacob S, Henriksen EJ, Tritschler HJ, et al. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabet 1996;104:284–8.
23. Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alphalipoic cid. Arzneimittelforschung 1995;45:872–4.
24. Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled, pilot trial. Free Rad Biol Med 1999;27:309–14.
25. Vincent HK, Bourguignon CM, Vincent KR, Taylor AG. Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. J Alt Complement Med 2007;13:577–84.
26. Konrad, op. cit.
27. Haupt E, Ledermann H, Kopcke W. Benfotiamine in the treatment of diabetic polyneuropathy—a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther 2005;43:71–77.
28. Winkler G, Pál B, Nagybéganyi E, Ory I, Porochnavec M, Kempler P. Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy. Arzneimittelforschung 1999;49(3):220–4.
29. Head KA. Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev 2006; 11(4):294–329.
30. Schalin-Karrila M, Mattila L, Jansen CT, et al. Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987;117:11–9.
31. Mansel RE, Pye JK, Hughes LE. Effects of essential fatty acids on cyclical mastalgia and noncyclical breast disorders. In Omega-6 Essential Fatty Acids: Pathophysiology and Roles in Clinical Medicine, ed. DF Horrobin. New York: Alan R Liss, 1990, 557–66.
32. Puolakka J, Makarainen L, Viinikka L, Ylikorkola O. Biochemical and clinical effects of treating the premenstrual syndrome with prostaglandin synthesis precursors. J Reprod Med 1985;30:149–53.
33. Pullman-Mooar S, Laposata M, Lem D, et al. Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid. Arthritis Rheum 1990;33:1526–33.
34. Jamal GA. The use of gamma linolenic acid in the prevention and treatment of diabetic neuropathy. Diabet Med 1994;11:145–9.
35. Horrobin DF. The use of gamma-linolenic acid in diabetic neuropathy. Agents Actions Suppl 1992;37:120–44.
36. Jamal GA, Carmichael H. The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial. Diabet Med 1990;7:319–23.
37. Keen H, Payan J, Allawi J, et al. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group. Diabetes Care 1993;16:8–15.
38. Ibid.
39. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med 1993;119:867-73.
40. Zurier RB, Rossetti RG, Jacobson EW, et al. Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum 1996;39:1808-17.
41. Keen op. cit.
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