Chapter 1 – Causes of peripheral diabetic neuropathy

Neuropathy can have many different causes, but diabetic neuropathy is mainly a disease of the metabolism. In other words, it is closely related to the breakdown and processing of nutrition.

In this chapter I will explain the most important modifiable causes of diabetic neuropathy.

I will leave out genetic causes, and other ones that can’t be changed. While such causes may be interesting perspective, they aren’t very useful in practical terms. We only need to concern ourselves with causes that we can actually do something about.

The high blood sugar theory

It has long been known that high blood sugar is one of the primary causes of diabetic neuropathy.² Lots of evidence support this view, for example the fact that diabetic neuropathy is common in both type 2 and type 1 diabetes, diseases which are different from each other. However, the most apparent common factor is high blood sugar.

Diabetic rats develop peripheral neuropathy, but this is reversible by bringing down blood sugar with the help of insulin.²

In type 1 diabetics, lower blood sugar (HbA1c) is associated with a lower risk of developing peripheral neuropathy.^{3, 4}

Improving (reducing) blood sugar levels in either type 1 or type 2 diabetics with neuropathy results in improved nerve function.⁵

Technically, high blood sugar contributes to oxidative stress and formation of so called advanced glycation end-products (AGEs) that damage the nerves.⁶

Therefore, the most important strategy to fight diabetic neuropathy in the long run – and it must be fought long term – is normalization of blood sugar.⁷ Furthermore, blood sugar variability can contribute to oxidative stress,⁷ so it’s better to keep blood sugar levels stable than spiking wildly.

Reducing blood sugar can be done in various ways, with insulin injections, diabetes drugs, lifestyle, diet, supplements etc. I will show you in this book what I think is the best way to keep blood sugar levels normal and stable, for both type 1, type 2 and prediabetics.

I’ve also written a full book that covers all important aspects of normalizing blood sugar naturally, for any diabetic. It’s called The Solution For Diabetes. I highly recommend you invest in a copy because it can show you how to significantly counteract diabetic complications, normalize blood sugar, and even control type 2 and prediabetes entirely.

While there is no doubt that high blood sugar (hyperglycemia) plays a role in promoting diabetic neuropathy, hyperglycemia alone cannot explain why diabetic neuropathy develops.

For example, feeding rats with unhealthy diets rich in sugar and fat, with or without a lot of salt, resulted in the development of painful neuropathy. Their nerves were damaged, and this was more evident when the unhealthy diet was also rich in salt. Interestingly, blood sugar levels only reached prediabetic levels (not diabetic), and the unhealthy diets did not cause any more weight gain than a normal diet. However, the rats on the unhealthy diets were characterized by insulin resistance, high insulin levels, high blood fats and, in the rats fed the salt-rich diet, high blood pressure.⁸

Another animal study, on mice, showed that overfeeding with a calorie-rich diet caused neuropathy, overweight and prediabetes, with high insulin levels and insulin resistance, and high blood fats. However, fasting blood sugar levels were not elevated.⁹

These studies demonstrate that

1. diabetic neuropathy can be caused by eating a poor diet
2. high blood sugar is not a requirement for neuropathy to develop
3. Other factors, such as high insulin levels, insulin resistance, high blood fats and high blood pressure are associated with the development of diabetic neuropathy

Indeed, in humans, insulin resistance, high triglycerides and low HDL cholesterol predict the development of diabetic neuropathy in type 2 diabetics.¹⁰

Diabetics with neuropathy have higher triglycerides than those without, and elevated triglycerides predict the development or progression of diabetic neuropathy.¹¹

So while high blood sugar promotes peripheral diabetic neuropathy, it doesn’t seem to be the only cause of it.

Diabetic neuropathy – an overfeeding disease?

Since high blood sugar alone does not completely explain the development of diabetic neuropathy, a broader explanation is clearly needed.

The most insightful theory I have seen is the one by Mikhail Blagosklonny, MD, PhD, Professor of oncology [cancer] at the Roswell Park Cancer Institute. Blagosklonny is one of the foremost authorities in the world on aging, and I pay attention to what he has to say.

He has published a highly interesting research paper on diabetic complications, including neuropathy.¹²

In his paper, he argues that diabetic complications are caused by mTOR activation. Basically, mTOR is a process in the body which is increased in the presence of:

• blood sugar
• insulin
• amino acids (i.e. protein)
• fats
• inflammatory molecules
• and more

In other words, he argues that diabetic complications are caused largely by overnutrition.

Eating causes blood sugar and insulin levels to rise, and increases the concentrations of amino acids and fats in the blood.

Insulin resistance, which is the hallmark of type 2 and prediabetes and common in type 1 diabetes as well, contributes to even higher levels of insulin and blood sugar, which activate mTOR.

That’s why diabetic neuropathy is common even in prediabetics,¹³ who haven’t yet developed the high blood sugar levels characteristic of type 2 and type 1 diabetics. However, prediabetics are characterized by insulin resistance and high insulin levels which, again, activate mTOR.

Ironically, even though we as a society are eating more and more calories, which is reflected in the obesity epidemic, many are also getting too few nutrients. A lot of diabetics are insufficient or deficient in various vitamins and minerals, which in itself contributes to diabetic neuropathy, or other types of neuropathy.

A healthier diet, with less calories but more nutrients, will go a long way towards improving diabetic neuropathy, diabetes itself, and other diabetic complications. This will be covered in detail in a subsequent chapter.

However, it is unrealistic to starve, and starvation can in fact contribute to neuropathy due to nutrient deficiencies. Fortunately, there is a diet that can mimic the effects of starvation, without actually causing any more hunger or forcing you to consciously limit your calorie intake.

In the chapter on diet, I will tell you about this diet that can also reduces mTOR, blood sugar, insulin, blood pressure, triglycerides, inflammation, and typically causes substantial weight loss in overweight individuals.

Other causes of neuropathy in diabetics

Just because a diabetic patient has neuropathy, doesn’t necessarily mean it’s diabetic neuropathy. Diabetes can cause neuropathy, but there are other causes of neuropathy as well, that are separate from diabetes.

It’s important, therefore, not to assume that all cases of neuropathy in diabetics are caused by diabetes. For example, alcohol abuse could be the cause of neuropathy in some diabetics that drink heavily.

While it’s outside the scope of this book to show you how to get rid of every kind of neuropathy, I can make you aware of some of the non-diabetes causes of neuropathy, so you can make sure to address them.

What follows are some of the most common non-diabetes causes of neuropathy, that can occur in diabetics as well as diabetes-free people.

An examination of 103 diabetics with peripheral neuropathy found that most of them (53%) had at least one additional factor that could cause neuropathy.¹⁴ Some of these factors were:

• Smoking. I have written an entire chapter on this that you can read.
• Nerve-toxic medications, such as amiodarone, colchicine, platinum chemotherapy
• Alcohol abuse
• Vitamin B12 deficiency
• End-stage kidney disease (when the kidneys no longer can perform their function adequately)
• Inflammatory bowel disease
• Rheumatoid arthritis
• Low vitamin B1 levels
• Low vitamin B6 levels
• High vitamin B6 levels

This is not a full list, but these were the most common findings. It’s probably wise to talk to your doctor about other potential causes of neuropathy, so you can be sure what causes your neuropathy.

For example, if you’re taking drugs that can cause neuropathy as a side effect, you may be able to find alternatives.

In this book, I will address some of these alternative causes of neuropathy, such as alcohol abuse, vitamin B1, B6, B12 deficiencies, as well as high vitamin B6 levels. I will do this just as a bonus for you. because it’s really outside the scope of this book.

If your symptoms still persist after implementing the strategies in this book, you may want to look for other causes of your neuropathy, as well.

Interestingly, both low and high vitamin B6 levels can cause symptoms of peripheral neuropathy. However, in the study at hand, 11 patients of 103 were B6 deficient, while only two had B6 excess.¹⁴ Both patients with excessive B6 levels were taking B6 supplements. Nevertheless, a deficiency of this vitamin is a much greater likelihood than an overload. I will address vitamin B6 in-depth in a subsequent chapter.

Alcohol abuse and neuropathy

Alcohol abuse can cause neuropathy.

In a study of 541 diabetics, 120 of them had an excessive alcohol intake. Among those with excessive alcohol intake, symptomatic peripheral neuropathy was much more common.¹⁵

Only drink low to moderate amounts of alcohol, which is probably unproblematic. I’ve seen no evidence a low alcohol consumption would contribute to neuropathy. However, for those who have been abusing alcohol, I think it’s best to cut it out entirely, to allow your nerves, and your body, to recover.

When alcoholism is the sole cause of neuropathy, nerve function typically recovers to normal or near-normal levels when alcohol intake is discontinued.¹⁶ However, it may take a few years.¹⁶

Alcohol abuse can cause nutrient deficiencies, e.g. vitamin B1, that contribute to neuropathy, and there is also a direct neurotoxic (nerve toxic) effect of alcohol.¹⁷

Cold exposure

Some studies found that foot temperature is higher in diabetics with peripheral neuropathy compared to non-diabetics.^{18, 19} The feet may feel uncomfortably warm.

If this is the case for you, it may be tempting cool your feet by various means, such as cold foot baths. However, this may not be a good idea.

In diabetic rats, cold exposure worsens the development of diabetic neuropathy,²⁰ and severe cold injury causes nerve damage, i.e. neuropathy, in humans.²¹

In one study, diabetic rats were forced to spend 3 hours per day, 5 days per week, on an aluminum plate which was either maintained at 10 degrees Celsius (50 Fahrenheit) or at room temperature (23 degrees Celsius or 73.4 Fahrenheit) for two different groups of rats, respectively. This went on for 20 weeks. At the end of the study, cold-exposed diabetic rats had reduced nerve function and had lost more nerve fibers than the room-temperature group.²⁰

The effect wasn’t huge, but nevertheless indicates that cold exposure is probably best avoided once diabetic neuropathy has already developed.

Interestingly, diabetic neuropathy is more common in diabetics living in cities with a colder temperature (measured in January),²² indicating that cold exposure may be a contributing factor to diabetic neuropathy.

However, cold exposure is not a requirement for diabetic neuropathy to develop, at all, but it may worsen the condition and it may be a contributing cause.

Whether warming the feet and hands would have the opposite effect, i.e. an improvement of diabetic neuropathy, is another question. I haven’t found any support for that.

Now, let’s look at how to improve diabetic neuropathy naturally.

Chapter 2 – Exercise

Exercise has long been recognized as a cornerstone of diabetes management, in terms of:

• improving blood sugar control
• reversing insulin resistance
• improving blood flow to hands and feet
• maintaining or losing weight
• reducing inflammation
• improving balance and muscle strength
• and numerous other health benefits.

However, exercise has remained controversial for folks with diabetic peripheral neuropathy.

Evidence is accumulating, though, that exercise can slow and even reverse peripheral neuropathy, and may reduce symptoms (e.g. pain) caused by diabetic neuropathy, as well.²³

Animal studies

In diabetic rats, swimming exercise or walking counteracts neuropathy.^{24, 25} In rats with diabetes and nerve injury due to physical harm, exercise helps them recover faster and counteracts negative changes in nerve fiber structure.²⁶ Prediabetic mice were found to be extra sensitive to pain, but allowing them to run in a wheel restored their normal pain thresholds.²⁷

However, some studies found harmful effects of land-based aerobic exercise in rodents with diabetic neuropathy.²⁸

Human studies

A 2013 meta-analysis pooled the results of 5 studies^29-33  that examined the effects of aerobic exercise on nerves of diabetics, and found that all studies reported a correlation between exercise and improved nerve health. Four of five studies measured nerve conduction velocity, a measure of nerve function, which showed an overall improvement.³⁴

That’s pretty impressive, since neuropathy is a progressive disease that seldom reverses spontaneously but usually gets worse as time goes by.

There were no serious adverse events reported in any of the studies, either.³⁴

To break these results down a bit more, exercise has been shown to prevent neuropathy from developing in diabetics,³⁰ and to reduce pain and other symptoms of neuropathy,^{31, 32, 35, 36} and to promote nerve fiber regeneration.^{31, 32}

Unfortunately, those with advanced nerve fiber loss in the skin may be less likely to achieve significant nerve regeneration with exercise.³¹

Another study on exercise for type 2 diabetics with neuropathy can be mentioned. One group of diabetics performed moderate intensity exercise on most days of the week, for a few hours per week in total, while another group remained sedentary. After 8 weeks, the exercise group experienced reduced pain, improved sensing ability in the feet, improved diabetic neuropathy symptoms, as well as better quality of life and nerve function, compared to the sedentary group.^{35, 36}

This study adds to the evidence that exercise is a useful therapy for diabetic neuropathy.

A word about Tai Chi

Tai Chi is a form of exercise that is based on far eastern movements, that are gentle and may be more appropriate for some diabetics. Tai Chi has been investigated for diabetics with neuropathy.

A Tai Chi exercise program tailored to diabetics (“Tai Chi for diabetes”) was found to reduce neuropathic symptoms, reduce pain, improve balance, and grant other health benefits.³⁷ This was achieved with 2 hours of Tai Chi per week for 12 weeks.

Another version, called “Cheng’s Tai Chi Chuan”, improved nerve fiber function and blood sugar in diabetics.³³

In one study, Tai Chi improved the ability to feel (sensory ability) in diabetics with loss of feeling in their feet.³⁸ It also improved balance and reduced HbA1c.³⁸

Tai Chi may be a more realistic exercise option for some people so, if you think it suits you better than other kinds of exercise, feel free to explore that. However, I don’t think there is any magic benefits of Tai Chi compared to other forms of exercise, so choose any form that you like.

Is exercise safe with diabetic peripheral neuropathy?

As always, nothing in life is completely safe, but if the right guidelines are followed, exercise should be safe and beneficial even for diabetics with peripheral neuropathy.

It was previously thought that diabetics with peripheral neuropathy should avoid weight-bearing activity, due to a supposed higher risk of foot ulcers (diabetic foot wounds), but research has not confirmed this suspicion.³⁹ (Weight-bearing activity is when the body weight rests on the feet, e.g. walking, jogging, standing, as opposed to, for instance, swimming.)

The American Diabetes Association (ADA) changed its stance on the issue, and now states that moderate-intensity exercise is fine for diabetics with peripheral neuropathy, as long as some precautions are followed.⁴⁰

Here’s my summary of the 2014 ADA recommendations with regards to diabetic neuropathy:⁴⁰

• Severe peripheral neuropathy or history of foot lesions might contraindicate exercise or predispose to injury. Health care providers should take this into account and customize exercise programs based on those considerations.
• Exercise may cause low blood sugar in individuals taking insulin or medications that increase insulin secretion.
• Moderate-intensity walking should not increase the risk of new or re-emerging foot ulcers in people with peripheral neuropathy. Two and a half hours of moderate exercise per week has been reported to improve outcomes in patients with milder forms of neuropathy.
• Anyone with peripheral neuropathy should inspect their feet daily to detect ulcers, and wear appropriate footwear.
• If any foot injury or open wound is present, activity should not be weight-bearing.

The report also recommended that any diabetic with peripheral neuropathy should undergo a “comprehensive foot examination” annually by their health care providers. It should include, among other things, visual inspection of the feet and tests for loss of feeling. So definitely start taking such an examination annually if you aren’t already.

Exercise guidelines

Based on the studies cited so far, and the opinion of the American Diabetes Association, I think that the following guidelines may be a good starting point:

• Choose a type of exercise that you like. Walking, swimming, stationary biking, strength training, elliptical machines etc. can all be beneficial.
• Don’t over-exert yourself. Avoid any extreme or high intensity exercise.
• Exercise for at least 2½ hours per week in total, divided on at least 3 days per week with max 2 days between sessions. More exercise is fine if you want to and can handle it.
• Some forms of exercise may evoke pain in diabetics with painful peripheral neuropathy. One study found that static contractions – i.e. keeping a muscle tensed for some time, such as when holding a heavy object – is more painful in diabetics with painful diabetic neuropathy than in diabetics free of neuropathy.⁴¹ In my opinion, avoid any activity or exercise that causes pain, because it’s the body’s warning signal that something is wrong.

This indicates that some types of exercise, such as static holds, may cause or exacerbate pain in diabetics with neuropathy, and may be best avoided.

• It’s wise to gradually increase physical activity, as it can allow the feet to adapt and make them less susceptible to injuries and ulcers.³⁹ The skin will get used to the mechanical movements and become thicker and more resilient.
• Make sure you have appropriate footwear. You may need to discuss this with an expert or your health care provider.
• Examine your feet daily. Minimize weight-bearing activity if you have wounds or ulcers, until they are fully healed. Seek medical advice immediately if you develop ulcers.
• Don’t perform any exercise that increases pain and neuropathy symptoms. Some individuals, may experience more pain due to exercise, although this seems to be the exception. Nevertheless, avoid things that worsen your symptoms. Try to find another form of exercise that doesn’t cause pain, perhaps swimming or some other gentle exercise.

Chapter 3 – Diet

As explained in the chapter on causes, nutrition has a lot to do with diabetic neuropathy. On one hand, it’s a disease of overnutrition. At the same time, it’s also commonly a disease of undernutrition, i.e. insufficient amounts of vitamins, minerals and certain other nutrients.

An appropriate diet can remove the underlying causes of diabetic neuropathy, such as high blood sugar, high triglycerides, high insulin, inflammation, and more. Anything to improve a disease must, of course, address the causes of the disease in order to be successful. That’s why this chapter is so important.

In fact, there is intriguing evidence that the composition of the diet may actually modulate the sensation of pain directly.

Can a diet really reduce neuropathic pain?

The idea that a diet can relieve pain may seem far-fetched, but there are several lines of evidence to back it up.

One of the conventional treatments, that doctors prescribe, for reducing pain caused by diabetic neuropathy is, believe it or not, antiepileptic medications – typically called anticonvulsants. You may know this already, and maybe you’ve been prescribed one of them.

Anticonvulsants have been used to treat painful diabetic neuropathy for several decades, and they are indeed effective for that purpose.⁴⁹

One proven treatment for reducing epileptic seizures is a so called ketogenic diet.⁵⁰ The ketogenic diet is, in other words, antiepileptic, just like anticonvulsant drugs.

A ketogenic diet is a very low-carbohydrate diet, characterized by virtually no carbohydrate.

It resembles the strictest phase of the Atkins diet, during which only 20 grams of carbohydrate are allowed per day – a very low amount. However, the Atkins diet allows unlimited amounts of protein, whereas a true ketogenic diet only allows normal amounts of protein. Hence, a true ketogenic diet has a very high proportion of fat.

Now, if antiepileptic drugs can effectively relive pain in diabetic neuropathy, and the ketogenic diet is antiepileptic, then it’s reasonable to think that the ketogenic diet could also reduce pain in diabetic neuropathy.

Interestingly, there is evidence from humans that a ketogenic diet can reduce the frequency and intensity of headaches and migraine attacks.^51-53

In rats, a ketogenic diet has been found to raise the threshold for pain caused by heat. After the rats were fed a ketogenic diet, a higher temperature was needed before the rats tried to withdraw their paws from a hot plate.⁵⁴ Sadly, this effect was not seen in mice, highlighting differences between species.

Ketogenic diets have been tested on rats with two kinds of neuropathy as well, either caused by deliberate injury to a nerve, or by cancer medication. Unfortunately, the ketogenic diet did not seem to reduce pain in either of those experiments.⁵⁴ At this time, no study has tested a ketogenic diet in diabetic neuropathy, either in animals or humans, so the effects are unknown.

The researchers behind some of the rodent experiments on ketogenic diets and pain concluded: “A ketogenic diet has not been but should be explored in diabetic neuropathy, particularly because recent evidence already suggests that a ketogenic diet can reverse diabetic nephropathy [kidney disease] in a rat. Furthermore, because it stabilizes a lower blood glucose [blood sugar], a ketogenic diet could limit or eliminate the need for insulin or other medications. Thus, a ketogenic diet could treat pain as well as multiple symptoms and consequences of diabetes.”⁵⁴ [emphasis added]

Taken together, I think it’s a likely hypothesis that consuming a ketogenic diet could reduce the pain caused by diabetic neuropathy, or other conditions, but we don’t know for sure until it’s tested in humans.

Whether or not the ketogenic diet is eventually proven effective for reducing neuropathic pain, it is still a good diet to follow for diabetics, which bring me to my next point.

Low-carbohydrate diets reduce blood sugar

Since high blood sugar promotes diabetic neuropathy,² it’s important to get your blood sugar levels under control.

Treating the symptoms without addressing the root cause is like trying to heat a house while all the windows and doors are open; it’s very ineffective. Just taking something to relieve the pain won’t leave you happy in the long run. Sure, it’s nice if the pain goes away, but if the nerve damage progresses there will still be other problems such as ulcers, loss of feeling, and amputations.

So, normalizing your blood sugar levels and keeping them stable is of key importance.

A proven way to do that is to reduce the amount of carbohydrate you eat.^55-76

The problem with following the high carbohydrate advice that is promoted by most diabetes organizations, dietitians, doctors, and so on, is that carbohydrate raise blood sugar levels by a large amount. Carbs are, in fact, the primary driver behind high post-meal blood sugar levels. Protein and fat, on the other hand, have comparatively little impact on blood sugar levels. The consumption of large amounts of carbs causes blood sugar levels to rise violently, and often unpredictably.

When you restrict your carbohydrate intake, your post-meal blood sugar levels will be lower. Fasting blood sugar levels frequently fall on a low-carbohydrate diet as well.

This is a logical and simple dietary maneuver, but you must be careful if you’re taking diabetes medications or injecting insulin, because reducing your carbohydrate intake while maintaining your usual doses of medications and insulin can cause low blood sugar. The fall in blood sugar when switching to a low-carb diet is usually immediate, so you have to be prepared for that and may need to reduce medications and insulin in advance. Definitely work with your doctor on this.

As described above, a ketogenic diet is simply a very low-carbohydrate diet with a normal protein intake. A low-carb diet might allow, for instance, 75 grams of carbohydrate per day, while a ketogenic diet typically allows only 20-30, or less. While many people on a low-carb diet eat large amounts of protein, a true ketogenic diet only allows normal amounts of protein.

There is no universal definition of the exact amounts of carbohydrate and protein allowed on a ketogenic diet, but the higher proportion of fat, the more ketogenic it is, which is beneficial. Of course, you still need to consume adequate protein, but that is rarely a problem.

Ketogenic diets have been successfully used to reduce weight and blood sugar in type 2 diabetics.^{59, 60, 71}

Another advantage of cutting out carbs is that overweight and obese individuals typically lose weight, without consciously restricting calories.^{76, 77} This happens because most people spontaneously eat less calories when carbs are restricted. After all, here’s just a partial list of foods that would be disallowed on a ketogenic diet:

• pizza
• hamburger with bun
• bread
• rice
• pasta
• potatoes
• sugar
• honey
• fruit
• fruit juices and sodas
• chocolate
• sweets
• ice cream
• beer
• cake, cookies, etc.
• cereals
• milk
• grains
• beans
• some nuts

That’s just a partial list but, when cutting out such carbohydrate rich foods, weight loss usually occurs because it’s difficult to eat as many calories as previously.

But, even if you don’t lose weight, a ketogenic diet is still effective for reducing blood sugar, compared to the commonly recommended carbohydrate-rich diet.

Effects of a ketogenic diet

In obese type 2 diabetics, a ketogenic diet (less than 20 grams of carbs per day) caused a greater reduction of HbA1c, greater improvement in cholesterol, and greater reduction of diabetes medications, compared to a low glycemic index diet containing 55% carbohydrate. Interestingly, the ketogenic diet group lost more weight, even though only the low glycemic index group was instructed to limit calories.⁷⁶

Other studies on overweight type 2 diabetics found essentially the same things: The ketogenic diet reduces weight, blood sugar, HbA1c, cholesterol and triglycerides.^{77, 78} All these are risk factors for diabetic neuropathy. Even when people are not instructed to consciously limit calories, ketogenic diets typically lead to larger weight loss and improved health, than diets with more carbohydrate.^{76, 77}

Again, there is no magic taking place. People typically eat fewer calories when carbohydrates are severely limited.

For a dramatic example of what can happen when obese type 2 diabetics go on a ketogenic diet, consider the following results. The ketogenic diet was followed for 56 weeks, restricted to 20 grams of carbohydrate per day for the first 12 weeks, and 40 grams thereafter.⁷⁸

• Average body weight fell from 238 lbs to 184 (108 to 83½ kg)
• HDL cholesterol increased over 50%
• LDL cholesterol fell by -33%
• triglycerides fell by -41%
• blood sugar fell by -51% (!)

In fact, their fasting blood sugar fell from 189 mg/dl to 88 mg/dL (10.5 mmol/L to 4.9 mmol/L); essentially from diabetic to normal.

You don’t have to eat a ketogenic diet, you could allow yourself a bit more carbohydrate if you want to, perhaps in the 75-100 gram range. But your blood sugar will most likely be higher if you eat more carbs. As described above, a ketogenic diet has been tested against a low glycemic index diet, as well, and the ketogenic diet was superior.

Furthermore, f you want to experiment with the potential pain-relieving effects of a ketogenic diet, then you need to reduce your carbohydrates to very low levels. No half-measures will do.

Type 1 diabetes and low-carb diets

A low carbohydrate diet is beneficial for type 1 diabetics as well.

A high carb diet makes it difficult to keep blood sugar levels in the normal range, because it’s difficult to estimate how much insulin will be required at meals. This depends on the entire composition of the meal, such as the amount of carbs, their glycemic index, and all the other ingredients, too.

Finding the right dose of insulin to inject at meal times, then, becomes virtually impossible. Add the fact that a high carbohydrate diet will require a high insulin dose; that’s just simple logic. But injecting higher doses of insulin increases the risk of low blood sugar episodes (hypoglycemia) which, apart from being unpleasant, can be outright dangerous.

The end result for type 1 diabetics is high blood sugar levels on a high carbohydrate diet, and often a great blood sugar variability, which itself may be a risk factor for diabetic complications.

However, on a low-carb diet, the post-meal blood sugar spikes are far lower and more predictable, thus requiring less mealtime insulin and the result is a much lower average blood sugar with less risk of hypoglycemic episodes (low blood sugar).

You might think that eating less carbs would result in a higher risk of low blood sugar, but the risk is actually reduced thanks to less insulin being injected. Injecting too much insulin is the main risk factor for experiencing hypoglycemia in type 1 diabetes, since it will reduce blood sugar too much. On a low-carb diet, that risk is smaller because less insulin is needed.

A low-carb diet has been tested in type 1 diabetics, so this is not just theory.

A medical clinic in Sweden taught 22 type 1 diabetics to follow a carbohydrate-restricted diet limited to 70-90 grams of carbs per day, and match insulin doses accordingly.⁷⁹ After 3 and 12 months on the low-carb diet, the number of hypoglycemic episodes were reduced by
-94% and -82%, respectively. In addition, the HbA1c level declined from 7.5% to 6.4% after 3 months, and remained there after 12 months. The mealtime insulin requirements were reduced by -40%, and the total insulin was reduced as well.

In addition, the overweight participants lost weight.

The 70-90 grams of carbohydrate per day is no “magic” level; it’s fine to reduce it to 40 grams if desired. That will result in even better blood sugar control, but many people feel that it’s too restrictive, that’s why the higher level was chosen.

The main objection that some people have to a low-carbohydrate diet is that it’s higher in fat. When carbs are significantly reduced, something else must account for the missing calories. That role is typically played by fat, since it’s unrealistic to eat a lot of protein. The “establishment” believes that dietary fat promotes heart disease but this is not supported by facts. In the study at hand,⁷⁹ despite replacing carbohydrate with calories from fat, the participants’ cholesterol levels did not change, and their triglycerides actually fell.

A longer term follow up of type 1 diabetics, who followed a low-carb diet for 4 years, more or less confirmed these results:⁸⁰ Those who stuck with the diet had lower HbA1c, higher HDL cholesterol and reduced heart disease risk factors. Interestingly, the doctors calculated that the reduction in HbA1c would be expected to prevent neuropathy in 5-6 persons out of the 23 studied.

Figure 1. Here’s a real-life example of blood sugar (blood glucose; BG) levels in a type 1 diabetic who switched from a normal to a low-carbohydrate diet as described above. “The arrow marks the change. There are 25 measurement over 6 days before the change and 39 measurements over 7 days after. Mean BG in the left side is 14.0 mmol/l [252 mg/dl] (range: 5.9 to 23.1 mmol/l [106 to 416 mg/dl]). Mean BG in the right side is 6.4 mmol/l [115 mg/dl] (range: 4.0 to 9.5 mmol/l [72 to 171 mg/dl]). It is evident that lowering of the mean blood glucose in the left side of the figure is impossible without hypoglycemia. Flattening out of the small spikes in the right side can be done safely.” Source: http://www.dmsjournal.com/content/4/1/23/figure/F1

Here is a brief summary of the low-carb diet prescribed by the Swedish doctors for type 1 diabetics: http://www.dmsjournal.com/content/supplementary/1758-5996-4-23-s1.pdf

However, there is nothing magic about exactly this kind of low-carbohydrate diet. A low-carb diet can be customized in numerous ways, so there is room for variation. I will provide more pointers later in this chapter.

When implementing a lower carbohydrate intake, be sure to work with a qualified health care provider, as you WILL  need to adjust (e.g. reduce) your insulin doses accordingly.

Do low-carb, high-fat diets promote heart disease?

Concerns have been raised that low-carb diets are dangerous and promote heart disease, because of their high fat content.

However, what we know for sure is that high blood sugar is dangerous, and that is the main problem facing diabetics. Dietary carbohydrate sends blood sugar soaring, while fat consumption has very little impact on blood sugar levels. So it’s not fat that diabetics should fear, but carbohydrate.

Indeed, a meta-analysis that pooled the results of 13 studies on type 2 diabetics, found that HbA1c, fasting blood sugar and triglycerides were reduced with lower carbohydrate content diets.⁸¹

Another meta-analysis, published 2009, examined the effects of varying the proportion of carbohydrate and fat, while keeping protein and calories the same.⁸² Nineteen studies on type 2 diabetics were included, and it was found that triglycerides and insulin resistance were lower, while HDL cholesterol was higher, on the low-carb diets. Carbohydrate tolerance was also impaired with high-carb diets compared to low-carb ones.

These analyses show that type 2 diabetics benefit from lower carbohydrate diets, which is just a confirmation of what common sense would tell us.

Low-carb and ketogenic diets and kidney disease

Kidney disease is a common complication of diabetes, and responds positively to a low protein diet.⁸³

Since low-carb and ketogenic diets are often higher in protein, some concern may be raised about their effects on kidney function.

However, there are several reasons why low-carb diets need not promote kidney disease.

First, you don’t have to replace carbohydrate with protein. It is best to replace most of the carbohydrate with fat or, alternatively, nothing at all so that you lose weight. Therefore, a low-carb diet should have a high proportion of fat, be very low in carbohydrate, and normal in protein. Of course, if you gorge on protein-rich foods, then that might be a problem for a number of reasons.

Second, diabetic kidney disease is promoted by high blood sugar, not just protein consumption, and low-carb diets are a great way to reduce high blood sugar.

Low-protein diets, on the other hand, are typically high in carbohydrate, which should be avoided with diabetes. So while their low protein content is good for the kidneys, their high carbohydrate content promotes high blood sugar which is detrimental to the body in a number of ways.

Third, studies on humans have shown that simply replacing red meat with chicken,^84-86 or chicken plus some white fish,⁸⁷ is also effective for slowing diabetic kidney disease, while still eating normal amounts of protein.

A diet where red meat, milk, cheese and eggs was replaced by cod has also been shown to increase insulin sensitivity, reduce inflammation and potentially increase insulin secretion.^{88, 89} I’m not saying you should only eat cod, but it seems like a good food to replace some red meat.

Fourth, in a very interesting and relevant study, 191 type 2 diabetics were assigned to either a low-protein diet or an experimental diet, to slow kidney disease.

The experimental diet was characterized by:

• NO red meat (it was replaced with fish, eggs, poultry, dairy and soy)
• A 50% reduction of carbohydrates from their normal level
• Only tea, water, milk and red wine allowed as beverages
• Only olive oil allowed for cooking and dressings
• The protein content was 25-30%; much higher than a low-protein diet

After 4 years, almost twice as many patients had developed kidney failure or died on the low protein diet.

The experimental diet, though much higher in protein, was vastly superior to the low protein diet for preventing kidney failure and death.

Finally, a study on mice with type 1 or type 2 diabetes, is worth mentioning. The mice developed diabetic kidney disease, as expected, and started dying on a normal diet (64% carbohydrate, 23% protein). However, after developing kidney disease, half of them were switched to a true ketogenic diet (5% carbohydrate, 8% protein, 87% fat) for 8 weeks. None of the mice on the ketogenic died. Moreover, their blood sugar was completely or partially normalized, kidney function was fully or almost fully restored, and even physical damage in the kidneys was starting to reverse when the study was ended.⁹⁰

The researchers believed that the ketogenic diet would be protective in diabetic neuropathy and possibly retinopathy (eye damage) as well,⁹⁰ but no studies have been done on that yet.

As you can see, lower carb diets are beneficial, not dangerous, for diabetics.

Of course, nothing in life is completely safe, and a low-carb or ketogenic diet can have side effects as well. The most important one is probably a sudden and dramatic reduction of blood sugar, which may require discontinuation or reduction of diabetes drugs and insulin, in advance. So you should always implement this together with a knowledgeable doctor.

As for protein content, it seems more important to avoid red meat than protein as such. Chicken and white fish seem much better alternatives. I still think, however, that you should not gorge on protein-rich foods. Normal amounts are fine.

Getting started on a lower-carb diet

Covering all aspects of a “low-carb lifestyle” is outside the scope of this book, but I will help you get started.

It’s up to you to decide how much carbohydrate you want to keep in the diet. Typically, I would say that lower is better, and if you want to try a ketogenic diet to get its potential pain-relieving effects, then you must eat very few carbs.

Here are basic lists of foods and drinks that I would recommend on a low-carb and ketogenic diet, respectively.

Diet summary

Diet is important for diabetics, since it affects blood sugar levels, inflammation, triglycerides, cholesterol, insulin levels, and more. One of the key goals in reversing diabetic neuropathy is the normalization of blood sugar. The simplest way to do that is eating a low-carb diet. It might not be enough to completely normalize blood sugar, but it’s a good step in the right direction.

Low-carb diets reduce blood sugar and typically promote weight loss among overweight and obese individuals – an added bonus. Weight loss will also improve numerous other risk factors for diabetic neuropathy, such as triglycerides, cholesterol, inflammation, etc.

Low-carb diets are not dangerous for diabetics. In fact, they are superior to high-carb (low fat) diets.

Heart disease risk factors are not negatively affected by low-carb, high-fat diets in diabetics; they are actually improved.

Kidney function should not be negatively affected by a low-carb diet, as long as you don’t gorge on protein. Keep protein foods at normal levels, and consume chicken and fish instead of red meat. Water, red wine, tea and decaffeinated coffee are good drinks, especially with meals, and olive oil is good for cooking and salad dressings. Generally speaking, carbohydrate should be replaced with fat.

A true ketogenic diet is a diet with normal amounts of protein, very little carbohydrate, and a very high proportion of fat.

Ketogenic diets may reduce pain directly. In humans, they can reduce headaches and migraine attacks; in rats, they can reduce pain generated by heat.

Ketogenic diets are antiepileptic, and antiepileptic drugs like pregabalin are effective for reducing pain in diabetic neuropathy. Therefore, ketogenic diets may have a similar pain-relieving effect in painful diabetic neuropathy, but research is still lacking in this area.

Diet may be the most important thing to focus on to fight diabetic neuropathy, and other diabetic complications, long-term.

Chapter 4 – Nutrients & supplements

In this chapter I try to show you some effective, scientifically-proven nutrients and supplements that can improve painful diabetic neuropathy.

Vitamin B1

Vitamin B1 is also known as thiamine. Another form of vitamin B1 is called benfotiamine which is just better absorbed than some other forms.⁹¹

Vitamin B1 levels are often reduced in diabetics, and taking oral benfotiamine supplements reduces symptoms (e.g. pain, numbness, etc.) of diabetic neuropathy.^92-94 It is also proven to reduce diabetic neuropathy symptoms in combination with vitamin B6,^95-97 or B12,^{92, 98} or B6 + B12.^{92, 99-101}

In diabetic rats, each of the individual vitamins B1, B6 and B12 has a positive effect on diabetic neuropathy, but the combination is more effective than either vitamin alone.¹⁰²

Benfotiamine alone,^{95, 99} and in combination with other B vitamins,¹⁰⁰ can improve nerve function, too (not just pain and other symptoms).

How it works is not entirely clear, because benfotiamine doesn’t typically reduce blood sugar or HbA1c.^92-94 However, it seems to counteract some of the harmful effects of high blood sugar.

Benfotiamine has other positive effects for diabetics as well. When type 2 diabetics were given a highly heat-treated meal – consisting of chicken, potatoes, carrots, tomatoes and vegetable oil – blood vessel dysfunction, inflammation and other negative effects were observed for several hours. This is because cooking with high heat for a long time creates harmful compounds. However, consuming 350 mg benfotiamine per day for 3 days prior to the same test meal partly or completely prevented those negative effects.¹⁰³

Even though benefits from benfotiamine can be felt very soon – some report improvement in neuropathy symptoms within 24 hours – the effect typically increases over weeks and months, so you may have to give it some time for the full benefits.⁹³

Benfotiamine is typically well tolerated without significant side effects.^{93, 94, 98}

Dose: Most human studies have used 100-600 mg/day. One study found that 600 mg/day benfotiamine was superior to 300 for reducing symptomatic (e.g. pain, numbness, burning) neuropathy.⁹³

Product with this nutrient: Doctor’s Best, Best Benfotiamine, 300 mg, 60 Veggie Caps (This product is the cheapest I have found. Take 2 capsules per day to get 600 mg/day.)

Other B-vitamins

If I had to pick one vitamin from the B family to take for diabetic neuropathy, it would be benfotiamine. However, other B-complex vitamins have also been studied for this purpose. The most promising are B6, B9 and B12. Especially their combination seems worthwhile to take.

The good thing about B-vitamins is that they’re generally quite safe, even at high doses. Side effects are infrequent, but you should of course always consult with your doctor before taking any. All disclaimers apply.

Vitamin B6 (pyridoxine, pyridoxal 5′-phosphate etc.)

Vitamin B6 levels may be lower in diabetics with neuropathy compared to diabetics without it,¹⁰⁴ and vitamin B6 deficiency can contribute to diabetic neuropathy.¹⁷

Vitamin B6 has rarely been examined on its own for diabetic neuropathy but, in a small study on diabetics who were undergoing dialysis, and had symptoms of neuropathy, vitamin B6 supplements for 4 weeks significantly reduced their symptoms.¹⁰⁵

However, in another small study on patients with diabetic neuropathy, vitamin B6 was no more effective than placebo.¹⁰⁶ This may have been because most of them had normal B6 levels to begin with.¹⁰⁶

Regardless, vitamin B6 has been included in numerous vitamin B-formulations that proved effective for diabetic neuropathy. Therefore, it is a worthwhile vitamin to take, since it also appears quite safe.

Vitamin B6 intake should not be greater than 200 mg per day,⁹⁹ because overdosing can cause a form of neuropathy. It is possible that too much vitamin B6 causes depletion of vitamin B9,¹⁷ which may contribute to neuropathy. That’s why vitamin B6 is best taken with other B-vitamins (see Metanx® below).

Pyridoxal 5′-phosphate is an active form of vitamin B6 and may be superior to other forms.¹⁰⁷

An appropriate dose, for diabetic neuropathy, seems to be 35-70 milligrams per day of pyridoxal 5′-phosphate, based on experiences with Metanx®. Based on available research, this should not cause any problems and should be beneficial (individual exceptions can always occur).

Vitamin B9 (folate, folic acid, L-methylfolate etc.)

Vitamin B9 is more often referred to as folate. Other forms are folic acid and L-methylfolate.

In humans with diabetic neuropathy, B9 has typically been given together with other B-vitamins, such as B6 and B12, which makes it difficult to determine the true role of folate itself. See the section on Metanx® below.

However, a recent study on diabetic rats found that folic acid injections, without other B-vitamins, partly corrected the nerve damage and symptoms of diabetic neuropathy, without lowering blood sugar.¹⁰⁸ This shows that B9 can most likely play a role in counteracting diabetic neuropathy in humans, as well.

L-methylfolate is a form of B9 seven times more biologically active than folic acid,¹⁰⁹ and may therefore yield better results.

Based on experiences with Metanx®, an appropriate dose for diabetic neuropathy seems to be 3-6 mg L-methylfolate per day.

Vitamin B12 (methylcobalamin, cyanocobalamin etc.)

As with other vitamins, there are different forms of vitamin B12, such as methylcobalamin and cyanocobalamin.

Methylcobalamin is the name of the activated, biologically usable, form or vitamin B12.¹¹⁰ Methylcobalamin may be superior to other forms of B12 for diabetic neuropathy.¹¹¹

Vitamin B12 has been shown to improve nerve function and symptoms (e.g. pain, and ability to feel) in patients with diabetic neuropathy,^110-112 and diabetic rats.¹¹⁰ It can also relieve neck pain, low back pain, and more.¹¹⁰

Overall, the results with only B12 aren’t extraordinary.¹¹¹ It may play a positive role in improving diabetic neuropathy, but relying exclusively on it may be too optimistic.

Of note, metformin – the common diabetes drug – depletes vitamin B12 levels in a dose dependent manner. In other words, higher metformin doses result in lower vitamin B12 stores in the body.¹¹³ Therefore, it’s important for metformin users to take extra vitamin B12.

Based on experiences with Metanx®, an appropriate dose for diabetic neuropathy seems to be 2-4 mg methylfolate per day.

Metanx® (vitamin B6 + B9 + B12)

Metanx® is an FDA-registered ”medical food” that consists of vitamin B6, B9 and B12. It’s actually not a ”food” at all, but a pill. Presumably, the reason for calling it a prescription food is to distinguish it from prescription drugs. Despite only containing vitamins, it requires a prescription in the United States.

A few studies have examined Metanx® on patients with diabetic neuropathy, with good results.

In one trial, patients with type 2 diabetes and neuropathy were randomly assigned to Metanx® or placebo for 24 weeks. The Metanx® group reported significant relief from neuropathy symptoms and improved quality of life, compared to placebo.¹⁰⁷ Negative side effects were rare.¹⁰⁷

In another small study of Metanx® given to type 2 diabetics with neuropathy symptoms, 73% of them experienced nerve fiber regeneration in the skin (an average of +97% fibers) and 82% experienced decreased neuropathy symptoms (e.g. burning, numbness, prickling, itching, reduced pain threshold etc.) after 6 months.¹⁰⁹

Finally, in a longer term study on patients with type 2 diabetes and painful neuropathy, 1 year of Metanx® treatment led to improved sensing ability in the feet. Interestingly, some patients reported an initial worsening of neuropathy symptoms (e.g. numbness, prickling, itching etc.) for several weeks before they improved.¹¹⁴

Metanx® supposedly contains superior forms of the vitamins, selected to be more potent.

Each capsule Metanx® contains:

• L-methylfolate Calcium (as Metafolin®) (vitamin B9)          3 mg
• Pyridoxal 5′-phosphate (vitamin B6)                                      35 mg
• Methylcobalamin (vitamin B12)                                             2 mg

The doses given in the studies were 1-2 capsules per day.

As mentioned, Metanx® requires a prescription in the United States. If you want to try it, definitely talk to your doctor about it. However, it is also possible to take each ingredient separately in the same doses.

I supposed it would be possible to buy each of the 3 ingredients separately for those who want to try that themselves.

It is simple enough to do a web search for each ingredient and find places to buy them Here are some examples:

Folate: Solgar, Folate, 1000 mcg, 120 Tablets (each tablet contains 1 mg Metafolin®)

Vitamin B6: Thorne Research, Pyridoxal 5′-Phosphate, 180 Veggie Caps (each capsule contains 33.8 mg pyridoxal 5′-Phosphate)

Vitamin B12: Jarrow Formulas, Methyl B-12, Lemon Flavor, 1000 mcg, 100 Lozenges (each lozenge is 1 mg methylcobalamin)

Resveratrol

Resveratrol is best known as a constituent of red wine and grapes, but also other foods such as peanuts. It’s a substance that seems to have various anti-aging properties, and it can help reverse type 2 diabetes in humans, as well as counteract neuropathy in rodents.

I’ve only found one study related to the treatment of diabetic neuropathy with resveratrol in humans, but it’s worth mentioning.

In the study, which was published in 2014, 24 type 2 diabetics with “diabetic foot syndrome” were randomly assigned to conventional treatment + resveratrol or placebo for 60 days.¹¹⁵

Diabetic foot syndrome is a serious, late complication of diabetes that is characterized by ulcers on the feet that are resistant to healing, which can lead to amputations and life-threatening infections, and the life expectancy in these patients is drastically reduced. Conventional treatments that promote wound closure are lacking, so anything that can help is a God-send.

Neuropathy is a significant risk factor for diabetic foot syndrome, and all the patients in the study suffered from neuropathy. Both groups improved during the study, but the resveratrol group had significantly better wound healing than the placebo group after 60 days. 36% of the resveratrol had complete wound closure after 60 days, vs. only 10% in the placebo group. Blood sugar levels also fell significantly in the resveratrol group only.

Here’s a link to photographic examples of the wound healing (WARNING: strong images. Do not click if you are sensitive to open wounds etc.):

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950537/figure/fig2/

The study was small, but well designed. Together with the evidence from previous trials that resveratrol counteracts neuropathy in rodents, and is helpful for type 2 diabetes in humans, I think it’s well worth trying.

It’s important to note that resveratrol was added to conventional treatments, not used alone. The results are, nevertheless, very encouraging and we will hopefully see more research on resveratrol for neuropathy in the future, as this is an emerging research field. Definitely continue the conventional treatments, too, if you have diabetic food syndrome.

Dose: The dose used in the study was 50 milligrams (mg) trans-resveratrol twice per day.

Products with this nutrient: The exact proprietary formula (by Lycotec) used in the study is not commercially available at this time, but here are some similar products containing trans-resveratrol. They should be effective as well.

• Doctor’s Best, Best trams-Resveratrol 100, 100 mg, 60 Veggie Caps (1 capsule = 100 mg resveratrol)
• Bluebonnet Nutrition, Age-Less Trans-Resveratrol, 250 mg, 60 Vcaps (1 capsule = 250 mg resveratrol)

Magnesium

Low magnesium levels are very common in diabetics; reportedly as many as 25 to 48% have low levels.¹¹⁶ Diabetics with peripheral neuropathy have even lower magnesium levels than neuropathy-free diabetics.¹¹⁶

This raises the question whether magnesium supplements are useful for diabetic neuropathy.

The evidence is mixed. Unfortunately, not too many studies have been performed on humans, but research on rats typically show positive results on neuropathy.

One study found that when patients suffering from neuropathic pain received either oral magnesium supplements or placebo for 4 weeks, there was no difference in pain or quality of life at the end of the study.¹¹⁷

However, 4 weeks is not a long time frame, and contrary results have been found in other studies.

In the largest study I have seen, 110 magnesium-deficient type 1 diabetics were randomly assigned to daily oral magnesium supplements, or no supplement. After 5 years, neuropathy was improved in 39% of the magnesium group (vs. 8% in placebo), unchanged in 49% of the magnesium group (31% in placebo) and worse in 12% of the magnesium group (61% in placebo). Yet, there was no difference in HbA1c between the groups, demonstrating that magnesium can reverse, halt or slow neuropathy via other mechanisms than blood sugar reduction.¹¹⁸

A small study on patients with neuropathic pain, not of diabetic origin, examined the effect of injected magnesium or placebo on two different occasions. The magnesium injection reduced pain significantly compared to placebo after just 10 minutes, with a greater effect after 20 and 30 minutes. Five of seven patients reported complete pain relief after magnesium, compared to none after placebo. Interestingly, this happened despite the magnesium concentrations being normal in all patients.¹¹⁹

Two weeks of intravenous magnesium injections followed by 4 weeks of oral magnesium supplements have also been proven effective in reducing chronic low back pain “with a neuropathic component”, compared to placebo treatment.¹²⁰ This study wasn’t performed on diabetic neuropathy patients, but another form of neuropathy was nevertheless involved in causing the pain.

Whether magnesium alleviates pain on its own or merely enhances the effect of other “pain killers” is controversial.¹²¹ There is a chance that, if you’re taking other medications to reduce pain, adding magnesium may improve their effect.

Considering how common it is for diabetics, especially those with neuropathy, to be deficient in magnesium, I think it’s a good idea to take a magnesium supplement.

Side effects (partial list): Magnesium is generally well-tolerated with few side effects.^{119, 120} The most common side effects reported are mild abdominal pain (9%), diarrhea (7%), nausea (3%).¹²² Some patients, such as those with kidney disease, should not take magnesium supplements, so definitely ask your doctor about this.

Dose: 300-400 milligrams of elemental magnesium per day appears appropriate based on studies on diabetics. This may seem high, but keep in mind that, typically, only 30-50% of magnesium supplements are absorbed. It can take 3 months for magnesium levels to increase even with supplementation.¹²³ Since diarrhea is a common side effect of magnesium supplements, take them in divided doses during the day. It will reduce the risk of diarrhea.

Products with this nutrient:

• Now Foods, Magnesium & Potassium Aspartate, 120 Capsules (each capsule is 150 milligrams elemental magnesium)
• Doctor’s Best, High Absorption Magnesium, 100% Chelated, 240 Tablets (each tablet is 100 milligrams elemental magnesium)

Dietary sources: Nuts and seeds are rich in magnesium. You can significantly increase your magnesium intake by eating nuts and seeds every day. Go for the kinds that are lowest in carbohydrate (e.g. Brazil nuts, macadamia nuts), and use them to replace carbohydrate-rich foods.

Acetyl-l-carnitine (a.k.a. l-acetylcarnitine or ALCAR)

Acetyl-l-carnitine (ALC) is a molecule that the body can manufacture, but taking extra ALC as a supplement has proven beneficial for various neuropathies, including the diabetic kind.¹²⁴

ALC does not merely relieve pain caused by neuropathy, but can actually promote regeneration of nerve fibers and improve vibration perception,¹²⁴ i.e. restoring sensing ability, an ability that can be reduced or lost due to neuropathy. Additionally, it generally appears safe with little side effects.¹²⁴

Several studies on humans have tested ALC for diabetic neuropathy.

In two of these, over 1300 patients with confirmed diabetic neuropathy were given 500 or 1000 mg ALC three times per day, or placebo, for 1 year. ALC led to reduced neuropathic pain compared to placebo, and an improved sensing ability in feet or fingers, as well as regeneration of nerve fibers.¹²⁵

In another study, 2000 mg/day of ALC given to diabetics for 1 year, led to improved nerve function and a -39% reduction in pain, compared to placebo (pain -8% with placebo).¹²⁶

Finally, a study examined the effects of injecting ALC or placebo in a small group of long-term diabetics for 15 days. They were all troubled by “symptoms of burning, shooting pain or tingling in the legs”. Placebo did not reduce pain, but ALC cut pain in half.¹²⁷ Injecting ALC might not be a viable option, unless you can convince your doctor to do that, but the study nevertheless shows that ALC is an effective treatment for symptomatic diabetic neuropathy.

ALC is generally safe and well-tolerated, at least in periods up to 1 year.^{125, 126}

Dose: 1500 to 3000 mg per day in divided doses have proven helpful in humans.^{125, 126}

Products with this nutrient:

• The cheapest product I’ve found is Primaforce, ALCAR, Acetyl L-Carnitine, Unflavored, 250 g Powder Each scoop is 500 mg.
• Another good choice is Doctor’s Best, Best Acetyl-L-Carnitine HCl, 588 mg, 120 Capsules Each capsule is 500 mg.

Alpha lipoic acid (a.k.a. thioctic acid)

Alpha lipoic acid (ALA) is good not only for weight loss and reducing insulin resistance, but also for reducing painful neuropathy. So that’s 3 good reasons for diabetics to take ALA.

In Germany, ALA is actually a standard treatment for neuropathy, and covered by health insurance companies.¹²⁸

In fact, ALA can reduce neuropathic symptoms by 50% in just 3-5 weeks,¹²⁸ which is quite impressive for a single nutrient, and better than placebo.¹²⁸

Dose: 600 mg per day seems sufficient to improve painful neuropathy.

Products with this nutrient: Healthy Origins, Alpha Lipoic Acid, 600 mg, 150 Capsules

Omega-3 fats

Omega-3 fats is actually an umbrella name for several different fatty acids (i.e. fats), with different properties. The most studied forms, which are considered most biologically significant, are alpha linolenic acid (ALA), EPA and DHA. EPA and DHA are only found in animal foods, such as oily fish or egg yolk. ALA is the plant form that can be converted to EPA and DHA in the human body, but not always in optimal amounts. That’s why extra fish oil, which provides preformed EPA and DHA, can be a good idea.

Only one study so far have examined the effects of omega-3 fats on diabetic neuropathy in humans.

EPA supplements were given for 11 months to 21 type 2 diabetics with peripheral diabetic neuropathy. Omega-3 improved various symptoms of neuropathy, such as coldness and numbness, and improved sensing ability in the feet. It also improved markers of kidney disease. Interestingly, arteries in the feet widened and blood flow in the feet increased during omega-3 supplementation.¹²⁹

Another series of case studies reported reduction of pain in 5 patients taking relatively high doses of fish oil for various pain syndromes, including fibromyalgia, carpal tunnel syndrome and burn injury. However, no patient had diabetic neuropathy. Nevertheless, there was a good improvement in pain and no serious adverse events were reported.¹³⁰

EPA and DHA are found together in natural foods but, in the study on diabetics cited above, they were given isolated EPA which is not possible without using supplements.

Therefore, we don’t know for sure if fish oil capsules, oily fish, or omega-3 rich plant foods would give the same result. The best bet for diabetic neuropathy, in my opinion, is either isolated EPA or fish oil. All fish oil contains EPA + DHA.

If you want to replicate the study design as closely as possible, take around 1800 milligrams of pure EPA per day in divided doses. There is a product called ”Pure EPA 1000” by Advanced Naturals that you can take 2 capsules of each day (1000 mg EPA per capsule).

However, I don’t believe such rigidity is called for. Increasing your intake of omega-3 rich foods, or simply adding a regular fish oil supplement would probably do the trick just as well.

EPA + DHA supplements (e.g. fish oil) are well-known for reducing triglycerides,^{129, 131-133} which is a risk factor for diabetic neuropathy. EPA or DHA, separately, also reduce triglycerides.¹³¹

The evidence for plant-based omega-3 for diabetics is much less clear, so it’s best to stick with fish oil supplements, or oily fish.

Side effects (partial list): Fish oil can thin the blood, which may be problematic, especially if you’re already taking blood-thinning medications. Additionally, it may be wise to discontinue fish oil two weeks before any surgery or dental work, to avoid excessive bleeding.¹³⁰

Suggested dose: The amount of EPA + DHA (combined) should be around 1000-2000 milligrams per day based on current evidence. Alternatively, eat oily fish a few times per week.

Products with this nutrient: Now Foods, Omega-3, Cardiovascular Support, 200 Softgels (4 capsules per day equal 1200 mg EPA + DHA)

Gamma linolenic acid

Gamma linolenic acid (GLA) is a fat that has beneficial effects on diabetic neuropathy.

This has been shown both in diabetic rats¹³⁴ and humans.^{135, 136}

In the first human study that I know of, 22 patients with diabetic neuropathy were randomly assigned to consume 360 milligrams GLA per day for 6 months, or placebo. Compared to the placebo group, the GLA group improved multiple measures of nerve function, as well as neuropathy symptoms, and sensing ability in the feet.¹³⁵

In a second, larger and longer, study, 111 patients with mild diabetic neuropathy were randomly assigned to consume 480 mg GLA per day for 1 year, or placebo. At the end of the study, 13 of 16 measures of neuropathy severity were significantly improved in the GLA group compared to placebo.¹³⁶

It’s difficult to purchase isolated GLA. It is usually sold as evening primrose oil or borage oil, since those oils naturally contain large proportions of GLA (9% and 24%, respectively). The highest concentration of GLA is found in borage oil, which I think is the most realistic option for the consumer.

An additional tip is to take GLA together with vitamin C, which makes it more effective.¹³⁴ However, if you’re going to take GLA + vitamin C, I suggest you take them both between meals. The reason is that vitamin C increases absorption of iron from food. Iron, in turn, promotes diabetes and diabetic complications. Vitamin C is good, but high iron levels are not. The full explanation for this is far too long for this book, but I cover it in depth in The Solution For Diabetes, my book on normalizing blood sugar naturally.

The appropriate dose of vitamin C in conjunction with GLA is unknown, but around 1500 milligrams vitamin C per day for an adult seems appropriate based on a rat study.¹³⁴ Again, consume the vitamin C between meals.

Side effects (partial list): Borage oil is usually safe to consume in normal amounts. One case report documented a woman that developed epilepsy after consuming 1500 to 3000 mg borage oil per day for a week.¹³⁷ Nevertheless, that is probably a very rare occurrence. Nothing in life is completely safe, and we’re all different, but I’ve consumed 1000 mg borage oil per day for months without ill effects.

Suggested dose: The human studies successfully used 360 or 480 mg GLA per day.

Products with this nutrient: Jarrow Formulas, Borage GLA-240, 120 Softgels (Each softgel is 240 mg GLA. 1-2 per day would be appropriate based on human studies.)

Zinc

High blood sugar is more common in men and women consuming diets low in zinc,¹³⁸ and zinc deficiency is more common among type 2 diabetics than healthy adults.¹³⁹

A few studies tested the effects of zinc supplementation on diabetic neuropathy.

In dialysis patients with non-diabetic neuropathy, zinc improved nerve function.¹⁴⁰

In patients with diabetic neuropathy, oral zinc supplementation for 6 weeks improved nerve function, lowered blood sugar and improved post-meal blood sugar, compared to placebo.¹⁴¹

The results were confirmed by another group of researchers who repeated virtually the same study protocol, and got the same results.¹⁴²

Diabetic rats develop nerve dysfunction and have a lower threshold for pain, but these effects are partly or completely prevented by giving them extra zinc.¹⁴³

Zinc supplementation is useful not only for diabetic neuropathy, but also for reducing blood sugar and HbA1c in people with elevated blood sugar, e.g. diabetics.^{144, 145} For more information, read my book The Solution For Diabetes.

Zinc supplements are typically bound to another substance, forming a so called zinc salt. The human studies on zinc for diabetic neuropathy used zinc sulphate (also spelled sulfate) (ZnSO₄), but other forms of zinc are presumably effective, too.

Suggested dose: The human studies used 660 milligrams per day of zinc sulphate. Zinc sulphate contains 23% elemental zinc.¹⁴⁶ Therefore, 660 mg zinc sulphate contains 152 mg elemental zinc. That is quite a high dose. Keep in mind that the human studies only lasted 6 weeks, so in the long run that dose may be excessive. It’s probably better to go with a lower dose long term.

There is a taste test to assess your zinc levels that you can use, but describing it in detail is outside the scope of this book. Do a web search for zinc taste test or similar and you will find more information.

Products with this nutrient: None at this time. Look for zinc sulfate tablets or liquid solution online or locally. As mentioned, other zinc salts are probably effective, too.

Vitamin E

Vitamin E functions as an antioxidant in the body, and that’s probably the explanation for its usefulness for diabetic neuropathy.

Vitamin E given to diabetics with peripheral neuropathy can improve their symptoms (e.g. pain)^{147, 148} and nerve function.¹⁴⁹

However, the results haven’t been super-impressive, and the doses were very high – a lot higher than the recommended daily intake for adults.

The average recommended daily intake of vitamin E for adults in the US is 15 milligrams per day, equivalent to 22.4 international units (IU).¹⁵⁰

One of the studies on diabetic neuropathy used 900 milligrams per day, 60 times the recommended daily intake. The safety of such high doses is questionable, especially long-term. Some analyses have found that vitamin E supplements can increase all-cause mortality, i.e. the total risk of death,^{151, 152} but other researchers found no such effect.¹⁵³

As for blood sugar control, vitamin E supplements reduce blood sugar and HbA1c in type 2 diabetics, but only if vitamin E levels are low to begin with.¹⁵⁴

It’s difficult to draw a definitive conclusion about vitamin E for diabetic neuropathy, but we can at least say that no diabetic should be vitamin E deficient. Since vitamin E supplements may be harmful in amounts higher than the recommended daily intake, I think it’s best to increase the consumption of vitamin E from food sources.

The most concentrated dietary sources of vitamin E are vegetable oils, nuts and seeds, and most margarines and spreads. Vitamin E is fat soluble, so it is found in high-fat foods. Fortunately, those foods are great for diabetics, since they typically contain low amounts of carbohydrate.

Here are some lists of good vitamin E rich foods for diabetics. Eating some of these foods daily will easily give you the recommended daily intake of vitamin E.

The lists are sorted from most to least per 100 g (3½ ounces) within each category.

Oils	Seeds and nuts	Other
Wheat germ oil	Sunflower seeds	Egg yolk
Sunflower oil	Pumpkin/squash seeds	Margarines and spreads (vitamin E not always present; read labels)
Canola/rapeseed oil	Almonds	Caviar
Olive oil, extra virgin	Hazelnuts	Avocado
Corn oil	Peanuts
Soybean oil	Cashew nuts
Coconut oil	Brazil nuts
Flax seed oil

 

Dose: The studies on vitamin E for diabetic neuropathy used doses from around 500 to 800 IU per day. But, as mentioned, such doses may increase the overall risk of death when taken long term, so it’s doubtful if that’s a good idea. I think that regularly eating foods rich in vitamin E is a better strategy.

Vitamin D

Insufficient vitamin D levels are very common among diabetics, more so than in diabetes-free individuals.¹⁵⁵

In a US survey of diabetics aged 40 years or older, 81% had vitamin d insufficiency.¹⁵⁶ That means that you, my dear reader, probably have insufficient vitamin D levels right now.

Vitamin D insufficiency is more common among Hispanics (92%) and blacks (98%) than whites (76%).¹⁵⁶ This, of course, has to do with the fact that much of our vitamin D levels are created in the skin in response to sunlight, and this synthesis is lower in people with darker skin.

Furthermore, vitamin D levels are even lower in diabetics with peripheral neuropathy than in neuropathy-free diabetics.^155-158 The same is true for diabetics with retinopathy,¹⁵⁷ i.e. damage to the retina in the eye due to diabetes, and foot ulcers, compared to diabetics without those complications.¹⁵⁸

As we can see, low vitamin D levels are associated with diabetes and diabetic complications, such as neuropathy. This raises the question whether vitamin D supplementation can improve those conditions.

Few studies have examined vitamin D for diabetic neuropathy in humans, although animal research is promising.

In one non-blinded study without a placebo control group, 51 vitamin D-insufficient patients with type 2 diabetes and painful neuropathy were recruited and given oral vitamin D supplements to restore adequate vitamin D levels. They were reexamined 3 months later. Vitamin D levels increased by 67%, while pain decreased by -39% to -49%, depending on how it was measured.¹⁵⁹

Another report describes a type 1 diabetic patient with peripheral neuropathy so severe that he had to stop working, despite taking several medications for the symptoms. He had low vitamin D levels and was started on 50 000 IU vitamin D₂ per week. Within 2 weeks his symptoms diminished and after 2 more weeks he could cut back on pain killers. His vitamin D levels tripled in that time.¹⁶⁰

Additionally, vitamin D was one of three active ingredients in a cream that effectively reduced symptoms of diabetic neuropathy.¹⁶¹

Taken together, the scientific evidence from humans that vitamin D supplements would reverse diabetic neuropathy or reduce pain is not very strong, so far. However, the facts are that:

1. vitamin D insufficiency is very common in diabetics
2. diabetics with complications like neuropathy have even lower vitamin D levels than those free of complications
3. restoring normal vitamin D levels is not harmful

Based on this, I think it’s prudent for diabetics with neuropathy to consume extra vitamin D. It could potentially lead to a big reduction of neuropathic pain, and no harm should come from it.

How much?

This question is very difficult to answer, because there is no agreement on the optimal blood levels of vitamin D. Even if there was, the amount of vitamin D to consume in order to reach them depends on sun exposure, consumption of vitamin D from food, body fat levels, and more.

Studies on type 2 diabetics have demonstrated that 1000 international units (IU) of vitamin D per day can reduce fasting blood sugar, HbA1c, insulin resistance, body fat and waist circumference, compared to placebo.^{162, 163}

One approach is to take a 25(OH)D test, also known as a 25-hydroxy-vitamin D test, and make sure it is at least above 30 ng/ml or 75 nmol/l. You can ask your doctor for this test, or go to a private clinic.

I think the best form of vitamin D supplements is called cholecalciferol, also known as vitamin D₃. It is widely available as a supplement, and is very cheap.

Dose: 1000 IU per day of vitamin D₃; higher levels may be more beneficial but can increase the risk of side effects.

Products with this nutrient: Healthy Origins, Vitamin D3, 1000 IU, 360 Softgels

Chapter 5 – Topicals

Topicals are things that are applied locally on the skin, such as creams, sprays, patches, lotions and so on.

As hard as I have looked, there aren’t many proven topical formulations that are realistic to use for diabetic neuropathy. The only one I found interesting enough to include is described below.

Capsaicin cream

Capsaicin is a component of cayenne pepper that grants the burning, hot, taste and sensation.

There are capsaicin-containing creams that are used for pain-reduction. Several studies on diabetics have found them effective for reducing painful diabetic neuropathy.^164-167

In a noteworthy study published in 1991, patients with diabetic neuropathy and moderate to very severe pain not responding to usual treatments, were given a 0.075% capsaicin cream, or placebo cream, for 8 weeks. The pain-reduction was greater in the capsaicin group, in which 90% of patients improved. The authors concluded that the capsaicin cream was ”safe and effective in managing painful diabetic neuropathy”.¹⁶⁵

Another study with the same design – 0.075% capsaicin cream or placebo cream for 8 weeks – confirmed these results: capsaicin cream is effective for reducing pain caused by diabetic neuropathy.¹⁶⁴ The cream was applied 4 times per day to painful areas.

Yet another 8-week study on 0.075% capsaicin cream found that it was as effective as the oral prescription drug amitriptyline – an antidepressant – in reducing pain in diabetic neuropathy. However, while the amitriptyline group experienced various side effects, the capsaicin group did not.¹⁶⁷

0.075% capsaicin cream applied four times per day can not only reduce pain, but also improve ability to work, walk, sleep and participate in recreational activities.¹⁶⁸

Capsaicin cream acts more as a pain-killer than a treatment that actually reverses neuropathy. Nevertheless, reducing the pain is helpful in its own right.

Capsaicin cream can cause burning, stinging and warmth at the site of application, but these feelings are typically reduced with continued use over weeks and months.¹⁶⁴ It is actually this initial triggering of nerve receptors, and their subsequent desensitization, that is believed to make capsaicin cream effective.¹⁶⁴ It should be avoided on open wounds.

Getting capsaicin on unintended areas, such as the hands, can cause intense burning and should be avoided. You should be extra careful to avoid getting it in the eyes or mucous membranes.¹⁶⁹ It’s a good idea to use rubber gloves when handling capsaicin cream.¹⁶⁹

Concerns have been raised that capsaicin cream would reduce the ability to feel pain caused by heat, which could lead to an increased risk of burn injury in patients treated this way.¹⁷⁰ However, this notion is controversial.¹⁷⁰ Two small studies found that capsaicin cream does not alter sensing ability in a detrimental way.^{166, 171} Other studies found that capsaicin does, in fact, raise the pain threshold,^{172, 173} which could increase the risk of injury due to the reduced ability to feel pain.

Nevertheless, even if there is a reduced ability to feel pain when using capsaicin cream, the effect is reversed when the treatment is discontinued. The effect doesn’t seem very large, either. It’s good to be aware, though, that the ability to feel pain, especially from heat, may be diminished when using capsaicin cream, and for several weeks afterwards. That’s why you should take extra care when you’re using capsaicin cream to avoid burn injury or mechanical injury to the areas you’re using it on.

Strength: Creams containing 0.075% capsaicin have been proven effective for diabetic neuropathy,^{164, 165} whereas a cream containing only 0.025% was ineffective,¹⁷⁴ so make sure you get one that is strong enough.

Frequency: Applying it 4 times per day to painful areas has been proven effective. Fewer times may also be effective; individual results may vary. You’ll have to experiment with this to find what suits you.

Dose: Follow the directions on the product.

Suggested products: Creams containing 0.075% capsaicin may require a prescription in some countries.

In those countries, 0.05% cream might be obtainable without a prescription. Always follow the rules and regulations in your country.

In countries where capsaicin creams are prescription-free, you can try the following product:

• Zostrix High Potency , Arthritis Pain Relief, Odor Free Cream, 2 oz (56.6 g) Tube
  It can be purchased on www.amazon.com

There are other capsaicin creams available from www.amazon.com

You can also do web search or ask your local health store for a 0.075% capsaicin cream.

Chapter 6 – Quitting Smoking

Smoking cessation, i.e. quitting smoking, is important for anyone, but even more so for diabetics with peripheral neuropathy, since smoking can decrease blood flow to the feet and hands. Unfortunately, many diabetics are unaware of the dangers of smoking, but it is clear that smoking worsens diabetes. For instance, smoking hastens the progression of kidney disease in diabetes, while cessation slows it.¹⁷⁶

Only one study that I’m aware of examined the effects of quitting smoking on diabetic neuropathy.

Smokers newly diagnosed with type 2 diabetes were encouraged to quit, and an examination of the results were done after 12 months.

Signs and symptoms of diabetic neuropathy improved significantly more among those who had successfully quit smoking, than among those who had continued, after 12 months.¹⁷⁷

The ”quitters” also had a significant reduction of blood pressure, blood sugar, HbA1c, insulin resistance, cholesterol, LDL cholesterol, and an increase of HDL cholesterol, compared to those who kept smoking. Kidney function also improved more among the quitters.

Nicotine itself is not good for diabetics, since it promotes insulin resistance, which is the hallmark of type 2 and prediabetes (see my book The Solution For Diabetes for more information).

Nevertheless, smokers who quit with the aid of transdermal nicotine patches still experienced improved risk factors for heart disease,¹⁷⁸ which demonstrates that nicotine replacement products are most likely healthier than outright cigarette smoking.

However, as mentioned, the best thing is to give up nicotine entirely. At least, do your utmost to stop smoking. Failure to do so could lead to quite serious consequences such as amputations (and many others).

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