This new paradigm relating to type II diabetes also influences contemporary therapy for the disease. Evidence now exists for a far more-aggressive approach to treating not just hyperglycemia, but also other cardiovascular risk factors such as hypertension, elevated LDL/triglyceride levels, low HDL levels, hormone imbalances, and central obesity in type II diabetic patients. The objective with multimodal therapies is to significantly reduce cardiovascular morbidity and mortality. While this is a worthy objective, chronically elevated glucose levels inflict damage to other parts of the body, which few doctors take steps to prevent.
To further complicate matters, the cells lining the blood vessels in diabetics suffer from a functional deficiency of thiamine, for reasons that are not yet fully understood. In essence, the very molecule (thiamine) that could help avert hyperglycemia-induced damage is itself broken down by the highly reactive molecules that are created in response to hyperglycemia. This catch-22 situation would appear to be cause for despair.
As discussed in this month’s “As We See It” column (“What You Don’t Know About Blood Sugar”), aging people with high “normal” fasting glucose levels also may be at risk for complications relating to sugar toxicity.
Slowing These Destructive Processes
All is not lost, however. Recently, scientists have begun taking a closer look at benfotiamine, a compound derived from thiamine. Used for more than a decade in Germany to treat nerve pain in diabetics, benfotiamine is fat soluble and therefore considerably more available to the body than thiamine.23,24
A landmark new study, published earlier this year in the medical journal Nature Medicine, found that benfotiamine increases transketolase activity in cell cultures by an astounding 300%. By comparison, when thiamine was added to cell cultures, transketolase activity increased a mere 20%. This robust activation of transketolase by benfotiamine was sufficient to block three of the four major metabolic pathways leading to blood vessel damage. Additionally, benfotiamine blocked activation of the pro-inflammatory transcription factor NF-kB. This suggests yet another beneficial attribute of benfotiamine.25
The study research team, based at the Albert Einstein College of Medicine of Yeshiva University in New York, further demonstrated that benfotiamine prevents damage to blood vessel cells cultured under hyperglycemic conditions in “test tubes” in the laboratory. Similarly, benfotiamine completely prevented retinal damage in live laboratory animals. “The data…indicate that treatment of diabetic patients with benfotiamine or other lipid-soluble thiamine derivatives might prevent or delay the development of diabetic complications,” concluded the authors.25
One of the team’s researchers is reportedly applying to the US Food and Drug Administration for permission to begin human trials of benfotiamine as a new drug. Although promising drugs do not always work as well in human subjects as they do in laboratory animal models, researchers are confident that benfotiamine will at the very least prove safe in humans. It has, after all, been used successfully in Germany for more than a decade to treat diabetic neuropathy, with no reported side effects.24
Small studies on human subjects conducted in Europe also show tantalizingly positive results. A study on human subjects in Hungary found that six weeks of benfotiamine treatment resulted in significant improvements in diabetic polyneuropathy in 93% of cases. Polyneuropathy is a painful condition that results when diabetes damages nerves in the extremities. The research team found benfotiamine therapy to be both safe and effective.26
Working along the same lines, a Bulgarian research team enrolled 45 diabetic patients in a three-month observational study to determine the efficacy of benfotiamine for the treatment of diabetic polyneuropathy. One group was given benfotiamine while the control patients received conventional B-vitamin supplements. The benfotiamine-supplemented patients experienced statistically significant relief of their pain symptoms, while patients taking vitamin supplements experienced no such improvement. Researchers noted that their results “underscore the importance of benfotiamine tablets as an indispensable element in the therapeutic regimen of patients with painful diabetic polyneuropathy.”27 They further noted that benfotiamine therapy resulted in no adverse reactions.
Given benfotiamine’s excellent, decade-long safety record among European patients, it seems safe to predict that even the most skeptical of clinicians will eventually be convinced that benfotiamine is both safe and effective for the treatment of dangerous diabetic complications. As patients’ waistlines—and numbers—continue to grow in the US and throughout the developed world, it appears certain that benfotiamine will win increasing numbers of fans.
Protecting Against Glycation and Carbonylation
The most effective natural inhibitor of protein carbonylation is carnosine, a dipeptide (the union of two amino acids) present at relatively high levels in muscle, heart, and brain tissue. Carnosine levels, however, decline with age. Carnosine reacts with and removes the carbonyl groups in glycated proteins.28,29 Moreover, carnosine suppresses the multiple pathways that lead to protein carbonylation. Carnosine’s anti-carbonylation mechanisms include chelation (sequestration) of copper and zinc, quenching of reactive aldehydes and lipid peroxidation products, and scavenging of hydroxyl radicals, superoxide, and the peroxyl radical. Carnosine inhibits glycation and especially AGE form-ation more effectively than the European pharmaceutical amino-guanidine (which is not available in the US), without toxicity. Carnosine’s copper-chelating ability, which is instrumental in AGE inhibition, is 625 times more potent than aminoguanidine.30
Several studies show that carnosine prevents protein cross-linking and AGE formation. In particular, carnosine inhibits the cross-linking of amyloid beta, which forms the senile plaques characteristic of Alzheimer’s disease.31 Carnosine protects neurons from the toxic effects of copper and zinc, which modulate synaptic transmission. In a recent double-blind, placebo-controlled study, carnosine im-proved the functioning of children with autistic spectrum disorders who were considered untreatable. After eight weeks on 400 mg of carnosine taken twice a day, the children showed statistically significant improvements on all measures in the Gilliam Autism Rating Scale. No children discontinued the study due to side effects. The authors suggest that carnosine may work by improving function of the neurotransmitter GABA through chelation of copper and zinc.32
Maintaining Youthful DNA Structure
A study of oxygen-induced chromosomal damage reinforces the connection noted earlier between protein carbonylation and chromosomal instability. Carnosine and several antioxidants were tested for their ability to protect cells exposed to 90% oxygen from chromosomal damage. Only carnosine exerted significant protection, reducing the level of chromosomal damage by two-thirds.33
Carnosine also prevented DNA fragmentation in liver cells exposed to hydrogen peroxide, an oxidant that is pervasive in the body, as well as in cells exposed to the tumor promoter TPA. The authors note the potential of carnosine in apoptosis-related disease, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s.34
Not only does carnosine rejuvenate cells—helping to keep skin and connective tissue supple and elastic, which gives skin a more youthful, wrinkle-free appearance and preserves muscle strength and vitality—but it also protects heart muscle from oxidation, thus warding off heart disease. Studies suggest that AGE-inhibitors like carnosine may generally become promising drug treatments for Alzheimer’s disease and even Parkinson’s disease,31,34 and also may prevent further injury and death in patients who have undergone coronary angioplasty.35
In prediabetes, a patient’s blood glucose levels are abnormally elevated, but not enough to warrant a diagnosis of type II diabetes. Prediabetes can be subdivided into two precursor conditions: impaired glucose tolerance and impaired fasting glucose. Although these conditions are believed to be reversible if addressed in time, most prediabetic patients experience few if any symptoms, and thus have no idea that they are at risk of developing diabetes. That is why it is so important to guard against sugar toxicity before a diabetic state manifests.
How Sugar Damages Cells
The problems associated with higher-than-desired sugar levels are myriad. Most stem from the central problem of excess glucose flooding into blood vessel cells. Fortunately, one of the body’s own enzymes, transketolase, is known to block the absorption of too much glucose. But to do its work, transketolase, requires the B vitamin thiamine as a cofactor. Unfortunately, thiamine (vitamin B1) is water soluble, which makes its less available to cells. Initial experiments have shown that the addition of thiamine to cell cultures bathed in excess glucose boosts the effects of transketolase, but only marginally.22 This suggests that scientists were on the right track, but that a thiamine derivative with better bioavailability might be needed to do the trick.