Benfotiamine - Managing diabetic complications yet with enormous anti-aging potential.

Other Articles: Overcome age-related diabetes with Benfotiamine

Benfotiamine has received great attention as a treatment for complications arising from diabetes. Before we learn more about Benfotiamine, we will first explore the diabetes condition.

Diabetes mellitus (often referred to simply as diabetes) is an incurable disease of the body’s endocrine system. It is characterised by a person’s inability to use glucose (blood sugar). The body uses glucose as its main source of energy. A diabetic person has high glucose levels due to the fact that either their body is not producing enough of the hormone insulin or because their body is unable to respond properly to the insulin that is produced.

Insulin is manufactured by the pancreas. Its role is to enable body cells to carry out glucose metabolism. It does this by opening glucose channels that allow glucose to move from the blood into the body cells. This absorbed glucose is then turned in to the energy that cells require. If glucose is not absorbed in this way it accumulates in the blood (this is known as being hyperglycaemic).

Types of diabetes

There are many types of diabetes. The two most well known variants of the disease are:

• Type 1 diabetes (sometimes referred to as juvenile diabetes or insulin dependent diabetes mellitus (IDDM)). When someone has Type 1 diabetes, they are unable to produce their own insulin because the insulin-producing cells in the pancreas have been destroyed by the body’s own immune system. Management of Type 1 diabetes requires the patient to inject insulin. The cause of this type of diabetes is unknown and the onset can often be very sudden. Whilst it can occur at any age, it is most likely to manifest itself in those under the age of 30 and tends to develop in childhood - hence the name juvenile diabetes.


• Type 2 diabetes (which used to be known as non-insulin dependent diabetes or mature onset diabetes). This form of diabetes results from insulin resistance i.e. cells fail to properly use insulin that the body produces. It is by far the most common form of diabetes accounting for around 85-90% of all diabetic patients. Although incurable, the risk factors for developing Type 2 diabetes are well documented. It is sometimes called a lifestyle disease because it is more common in people who do insufficient amounts of exercise and who are overweight or obese - especially those who are apple-shaped and carry excess weight around the waist. It is also strongly associated with high blood pressure, high cholesterol, an unhealthy diet and smoking. Other risk factors include such things as being a Pacific Islander, Chinese or from the Indian sub-continent and being a woman who has previously suffered from gestational diabetes. Whilst Type 2 diabetes usually affects mature adults (particularly those over the age of 55), younger people are now increasingly being diagnosed with the disease as rates of overweight and obesity increase.

Symptoms of diabetes

Both Type 1 and Type 2 diabetes have a number of common symptoms that they share including:

• Increase in thirst (excessively so for Type 1 diabetes)
• More frequent urination
• Fatigue and lethargy
• Itchy skin
• Visual disturbances such as blurred vision

Type 1 also displays symptoms such as hunger, weight loss, nausea and vomiting. However, with Type 2 diabetes the disease may be completely symptomless or, even if symptoms are present, they are often not recognised as such and simply put down to such things as growing older or being busy. This means that around half of those who have Type 2 diabetes remain undiagnosed and in many other cases the disease is not picked up until glucose levels have become very high.

How widespread is diabetes?

What is probably most worrying is that we appear to be in a “diabetes epidemic”. The total number of people worldwide with diabetes has been projected to rise from an estimated 171 million in 2000 to 366 million in 2030(1). The most important demographic reason for such a rise is in the ever increasing proportion of the world’s population over the age of 65 but what is perhaps even more alarming is that the projected estimate for 2030 was based on obesity levels remaining constant. Given the increasing prevalence of obesity, it is likely that this figure underestimates future diabetes levels.

Complications that can develop as a result of having diabetes

There can be no doubt that having diabetes increases your risk of developing a number of potentially catastrophic complications that can severely damage many systems, tissues and organs in your body. Complications include the increased likelihood of infections, poor circulation in the legs and feet that can lead to amputations, damage to the nerves of the feet, significant increased likelihood of heart disease and stroke, sexual impotence, damage to the eyes and kidney damage.

Most of these complications occur because of prolonged hyperglycemia (high blood sugar) that’s due to poorly controlled blood glucose or to disease progression over time. The body deposits excess blood glucose into the nerve cells and the small blood vessels of the extremities. There are four main separate biochemical pathways that that occur in the body that can lead to small blood vessel damage due to hyperglycemia:

• i. the production of advanced glycation products (AGEs)


• ii. the activation of protein kinase C


• iii. the activation of the hexosamine pathway


• iv. the activation of the polyol pathway.
We mention these biochemical pathways again later.

And if you were in any doubt as to how serious these complications can be, take for example the results of a study published in 2005 where it was concluded that not only was diabetes globally the 5th leading cause of death in 2000, diabetic complications involving the finer blood vessels (microvascular complications) accounted for a significant portion of these deaths (2). In the United States diabetic retinopathy, nephropathy, and neuropathy are the leading causes of blindness (between 12,000 to 24,000 Americans go blind each year because of diabetes).

And it is these last three complications of retinopathy, nephropathy and neuropathy that we will concentrate on for the remainder of this article.

What is diabetic retinopathy?

If blood glucose levels remain too high over a long period of time, changes can occur in the tiny blood vessels that supply the eye’s retina. Dark spots and strange blotches may appear in an affected person’s vision. Their vision may also become blurred. If left untreated, it can result in blindness.

What is diabetic nephropathy?

Nephropathy is a long-term complication of diabetes. It occurs when small capillaries (the smallest blood vessels in the body) in the kidneys become damaged from years of high blood glucose levels and/or high blood pressure. This results in the kidneys losing their ability to filter blood effectively which in turn means that toxins and excess proteins can build up in the blood. It is a progressive condition which, if left untreated, can lead to kidney failure and the need for dialysis.

What is diabetic neuropathy?

Neuropathy refers to nerve damage. In cases where a person has uncontrolled high blood sugars over a long period time (which can be especially true in the case of someone whose diabetes was symptomless for many months or even years) nerve damage can develop. This may manifest itself in a number of ways - sensation becomes abnormal and tingling and burning pain can develop. Where damage occurs to the nerves in the skin, a person may suffer more damage because they are unable to feel changes in temperature or pressure. Neuropathy is most likely to develop in the hands and feet.

Clearly these three complications are very significant and can have devastating consequences. Whilst diabetes remains incurable, trying to prevent complications such as these from occurring - or where they have occurred to try and limit their progression and severity, has been a highly desired goal. And a study published in 2003(3) brought benfotiamine sharply into focus in this regard.

What is Benfotiamine?

Benfotiamine (sometimes called benfothiamine) is a man-made fat-soluble compound that is a derivative of the water soluble B-complex vitamin, Vitamin B1. Vitamin B1 is also known by the name thiamine (may be spelt thiamin). Being water soluble, thiamine is not as easily used by the body as fat-soluble benfotiamine which can be better absorbed and utilized.

What is the relationship between benfotiamine and diabetes?

It was not until Michael Brownlee et al’s paper (3) was published in the journal Nature Medicine in February 2003 that benfotiamine really came to the world’s attention with regard to the possibility of preventing the development and progression of diabetic complications. Brownlee and his team had discovered that benfotiamine had the ability to simultaneously inhibit three of the above mentioned major biochemical pathways implicated in the development of hyperglycemia induced vascular damage - in other words they had discovered that benfotiamine could block the damage triggered when cells are exposed to high concentrations of sugar.

They were able to demonstrate that benfotiamine prevented the development of retinopathy in diabetic rats, which raised the hope that this previously overlooked compound would be able to do the same for people.

Since then benfotiamine has undergone several studies with the main focus being the use of benfotiamine as a treatment for diabetes complications. These studies have shown that benfotiamine appears to be able to help prevent or slow the development of neuropathy, retinopathy and nephropathy by inhibiting the build-up of glucose in blood vessels.

Other uses for Benfotiamine

One of the theories behind why we age in the way that we do is based on the gradual formation of advanced glycation/glycosylation end products (or AGEs) which in turn can damage many of our body systems, organs and tissues. Glycation (sometimes called non-enzymatic glycosylation) occurs every day as part and parcel of the body’s normal metabolic processes. It is a series of chemical reactions that occur when protein molecules bind to sugar molecules. Glycation is a haphazard process - where enzymes control the process it is known as glycosylation. A whole cascade of chemical reactions occurs during glycation/glycosylation which ultimately results in the formation of advanced glycation (or glycosylation) end products (AGEs). While some AGEs are benign, the majority are extremely harmful.

Research suggests that many chronic age-related degenerative diseases such as cancer, cardiovascular disease, cataract problems and Alzheimer’s may all be associated with the havoc and destruction that a steady accumulation of AGEs over time can cause.

Take for example cardiovascular disease. AGEs can lead to the stiffening and weakening of collagen in blood vessel walls. This type of stiffening leads to high blood pressure and the weakening can result in an aneurism (a weak spot in the wall of an artery or a vein that dilates or balloons out to form a blood-filled sack or pouch). If an aneurism bursts, a massive amount of blood is released, which results in an almost instantaneous drop in blood pressure that can lead to death. If a burst occurs in the brain, it can result in a stroke. AGEs can also affect the amount of LDL (bad) cholesterol that gets deposited in blood vessel walls and in time this can also result in atherosclerosis which is the root cause of various cardiovascular diseases such as angina, heart attack and stroke.

Of course, for someone whose blood system is bathed in too much glucose, as is the case with diabetes, AGEs are formed far more quickly. Watching someone with diabetes is in effect like watching someone age in fast forward.

Treatment with benfotiamine, has however been proven to reduce tissue AGEs. This is due to the fact that benfotiamine leads to significantly increased intracellular thiamine diphosphate levels. Thiamine diphosphate is a co-factor in the enzyme transketolase and it’s transketolase that works to reduce tissue AGEs. Using thiamine (Vitamin B1) alone to increase transketolase levels does not work efficiently enough to stop AGEs from accumulating in healthy cells. But benfotiamine can increase transketolase levels by as much as 300%! The implications of this in relation to anti-aging medicine are potentially enormous.

Benfotiamine, in combination with pyridoxine hydrochloride, has also been used for a number of years by doctors in Germany to treat nerve damage and nerve pain such as sciatica.

Whilst research into benfotiamine continues, even at this stage we already know enough to understand its potential and the fact that ultimately benfotiamine may have a huge impact on the lives of so many.

Dosage

50mg doses should be taken two or three times daily. Type 1 diabetics may need to increase their doses to 100mg.

References

1. Wild S, Roglic G, Green A, Sicree R, King H. Global Prevalence of Diabetes. Estimates for the year 200 and projections for 2030. Diabetes Care 2004 27:1047–1053
2. Roglic G, Unwin N, Bennett PH, Mathers C, Tuomilheto J, Nag S, Connolly V, King H. The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care 2005 Sep;28(9):2130-5.
3. Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, Lin J, Bierhaus A, Nawroth P, Hannak D, Neumaier M, Bergfeld R, Giardino I, Brownlee M. Benfotiamine blocks three major pathways of hyperglycaemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003 Mar;9(3):294-9. Epub 2003 Feb 18.

 

Overcome age-related diabetes with Benfotiamine

Benfotiamine, a synthetic variant of vitamin B1, can help prevent nerve and blood-vessel damage caused by diabetes. Two of the main impacts of diabetes are circulatory difficulties and vision problems. These symptoms are caused by a build-up of sugar in the tissues. As there are considerable changes in insulin and glucose tolerance with age – sometimes referred to as age-related diabetes – similar symptoms have often been considered part of the aging process.

Now researchers have reported that Benfotiamine halts much of that sugar accumulation. This could result in a vastly improved quality of life for those with the disease and those suffering the age-related symptoms.

Much of the damage of diabetes is caused when glucose-derived compounds, called triosephosphates, accumulate in vascular and nerve cells. The activation of the enzyme transketolase, turns triosephosphates into chemicals that are harmless.

Transketolase is a thiamine-dependent enzyme, so it has been thought that thiamine, (also known as vitamin B1) could activate Transketolase. But, thiamine only activates it at level around 20%, which isn't enough to stop the glucose-derived compounds accumulating in healthy cells. However, recent research has found that Benfotiamine increases the levels of transketolase by 300%!

While its action has not been tested on the process that controls nerve cells, it is thought that it may work similarly there. Even so, whatever the outcome of that research, we already understand enough about Benfotiamine to realise that it can prevent many diabetes-related complications.

Dosages:

Dosages are 50mg two or three times daily, although type-I diabetics may need to increase doses to 100mg.

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