Bitter Diagnosis, Sweet Therapy?
Biochemist Werner Reutter studies whether galactose is an effective treatment for dementia – and has been fighting for a clinical trial for years.
Mar 30, 2016
Nowadays, there are very effective treatments for many serious illnesses. But there is still no sign of an effective treatment, let alone a cure, for dementia – especially Alzheimer’s disease. And how could there be, when even the experts don’t agree on the cause? Defective tau proteins, some say, while others believe the blame lies with a type of protein called amyloid beta that has clumped together into threadlike shapes known as fibrils.
To Werner Reutter, a longstanding medical researcher at Freie Universität Berlin and a biochemist, both approaches merely involve researching the symptoms of the disease, not its root cause. “The typical plaques found in the brains of Alzheimer’s patients are not the trigger, but rather the effect of a malfunction,” he says.
It is a fact that proteins are deposited in the brains of older people – but not all of them come to suffer from dementia; far from it, in fact. Among those under 75 years of age, the figure is just 3.5 percent. It rises to just under 16 for those between 80 and 84. It is not until after a person’s 90th birthday that the figure rises steeply, to nearly one-half. Fewer than two percent of people already carry Alzheimer’s disease in their genes; the rest develop it sporadically. Studies have shown that diabetics are at elevated risk of dementia, as are people who suffer from depression.
Back in the early 1990s, Siegfried Hoyer, a neuroscientist working in Heidelberg, proposed that dementia could be a metabolic disorder, a kind of “type 3” diabetes. Werner Reutter, an expert on the biochemistry of sugar, and his team think so, too. “We believe defective insulin receptors in the brain are the cause,” he says. Recent studies, including by American gerontologist Auriel Willette, support this view. Willette was able to show in 186 test subjects (average age: 60) that insulin resistance is present in the cells of the brain for a long time before the plaque forms. This means that the brain cells can no longer absorb adequate amounts of glucose from the blood even though the body is producing enough insulin.
As Ronald Kahn of the Joslin Diabetes Center in Boston recently showed, diabetes, dementia, and even depression seem to have one thing in common: defective insulin receptors. Mice who lack the gene for the receptor in their brains become anxious at advanced ages and seem depressed. They increasingly form enzymes that break down dopamine, a substance involved in the reward cycle. Parkinson’s disease is also marked by a lack of dopamine. This immediately leads researchers to suspect that insulin resistance in the brain could be what triggers this disease as well.
Plausible Scenario for Emergence of Alzheimer's
At least one conclusive scenario for how Alzheimer’s disease arises seems to fit together logically at this point: If not enough glucose reaches the brain cells, the neurons lack the power to perform their tasks. Among other things, they can no longer break down used-up proteins in a timely fashion. Waste builds up around the cells, plaques form, and the nerve cells affected die off as a result.
Although the brain makes up only two percent of an adult’s body weight, it uses more than half of the carbohydrates consumed in a day – or, more specifically, the glucose they contain. Another sugar that is almost identical in chemical terms – galactose, an element of lactose – reaches the cells via a different route regardless of the insulin receptor and is enzymatically converted into glucose there.
So could a simple sugar be the solution for dementia? Together with Melitta Salkovic-Petrisic, a pharmacologist working at the University of Zagreb, Reutter has been able to show in rats that if the insulin receptors in the animals’ brains are blocked chemically and the animals are then given galactose in their drinking water, they do not lose their memory. By contrast, animals in another group were given plain water and soon could no longer find their way to the feeding dish.
First Trials Look Promising
The first few experiments involving offering galactose as a substitute to the potentially starved brain cells of people suffering from dementia have been very promising, Reutter explains. “I myself saw a whole series of patients who take it. Their orientation, recall, and social communication skills improve markedly. There is no currently approved medication that can compare.” One teaspoon of the sugar, dissolved in tea, water, or coffee three times a day, was enough.
Reutter – who is now 78 years old and still doing research work for Charité – has been trying to raise funds for a clinical trial of galactose for as long as the diabetes theory of Alzheimer’s disease has existed. The goal is to perform a scientific study of the sugar’s efficacy as a treatment and rule out any possible undesirable side effects. So far, though, all his efforts have been futile. He says that neither the pharmaceutical industry nor health insurers are interested. Why not? “Because there’s no money in galactose. It’s not a drug, it’s ‘just’ a sugar substitute,” Reutter says bitterly.
The substance, whose formal chemical name is “D-galactose,” is a natural monosaccharide, or simple sugar, just like glucose – and it is freely marketable as a nutritional supplement: 250 grams costs 40 to 50 euros. The acetylcholinesterase inhibitors that are often prescribed as a treatment for dementia at present cost the health insurers much more. “But all they are is expensive – they hardly work at all,” Reutter says with a shake of his head. In addition, medical researchers (and the drug industry) are currently pinning their hopes on a lucrative vaccine for Alzheimer’s disease. The vaccine is supposed to prompt the immune system to form antibodies that fight the plaque. It is a vaccine for a symptom, but not the cause, Reutter criticizes.
Available without a Prescription in Pharmacies
Galactose is already available over-the-counter right now. It is not quite as sweet as cane sugar, or sucrose, and it is derived in pure form from lactose. Whey is the usual source. Couldn’t one simply drink a lot of milk or eat large amounts of cheese and yogurt instead? “No, because galactose is not absorbed by the cells unless there is enough of it in the blood,” Reutter explains. “Even pure lactose wouldn’t do anything. About ten percent of Europeans are lactose-intolerant, and in the other 90 percent, the enzyme that splits lactose in the intestinal tract is not active enough to release sufficient galactose.”
Unlike most medications, this specific form of sugar only has side effects if people really overdo it, Reutter says. That means the idea that consuming more leads to better effects does not apply here. “People should only take as much as the body can metabolize in a day. Otherwise, you can get a situation like with the rare genetic defect galactosemia, which newborns are routinely tested for,” he explains. One in every 40,000 people is born with this condition, in which the enzyme needed to break down galactose is absent. If too much of it builds up in the blood, cataracts can form. “But three teaspoons a day is much too little for that,” Reutter stresses.
Suitable for Lactose-intolerant People
Galactose is suitable even for those with lactose intolerance. It only has a laxative effect if consumed in excess. And even diabetics can take the sugar, since it does not raise their blood sugar levels. Whether galactose, taken prophylactically at the first sign of dementia, could help to prevent dementia is still speculative at this point, since clinical trials have not yet been performed. Reutter himself takes the sugar regularly, with a much shorter-term goal in mind: “Galactose gets rid of the afternoon slump,” he says.
Competitive athletes have known that for a long time. They value this form of sugar because it reaches the cells independent of insulin, delivering fresh energy to muscles suffering from acidosis. If an athlete overexerts himself or herself, lactic acid and ammonia form in the body. Ammonia blocks the insulin receptor. This is another point that supports the diabetes theory, Reutter says, “According to recent studies, Alzheimer’s patients also have elevated ammonia levels.”
Reutter began studying the galactose metabolism back in the late 1970s. He studied liver tumors in mice at the University of Freiburg. Later, at Freie Universität, he focused on hepatic encephalopathy, a brain disorder that arises when the liver can no longer break down ammonia. Even back then, Reutter already knew that galactose could help cells that are hungry for sugar, and he convinced a gastroenterologist at Freie Universität to give his patients galactose on a trial basis. The doctor was astonished to report that the patients responded much faster to the new treatment than they did to the customary glucose infusion.
Like ammonia, endotoxins that form in cases of blood poisoning (sepsis) also poison the insulin receptors. Initial results of a German pilot study of 70 patients show that galactose is very effective at fighting sepsis. If Reutter had his way, a Max Planck Institute dedicated entirely to galactose and the insulin receptor, which has been underrepresented in research in the past, would have been established long ago. Since this kind of receptor is found in almost every single cell in the body, Reutter thinks it is likely that galactose is also effective at treating other, completely different diseases. It wouldn’t be the first time that nature itself offered a simple and ingenious treatment.
Prof. Dr. Werner Reutter, Institute of Biochemistry and Molecular Biology, Email: Werner.Reutter@Charite.de