It’s official: The ketogenic diet was shown to be effective in controlling polycystic kidney disease (PKD) in the first randomized controlled clinical trial of ketogenic metabolic therapy for PKD.
“I’m really happy about these clinical trial results,” said UC Santa Barbara biologist Thomas Weimbs, whose lab was part of an international collaboration investigating the effect of the fasting response known as ketosis on cysts that is the hallmark of the disease. . . “Now we have the first evidence in humans that cysts don’t really like being in ketosis and they don’t seem to grow.”
The researchers’ study is published in the journal Cell Reports Medicine.
Nurture over nature
For PKD patients, these findings represent an opportunity to control a genetic disease that leads to a progressive condition, causing pain and robbing them of their quality of life and often leading to the need for dialysis and a kidney transplant as the cysts destroy the kidneys.” ability to effectively filter and remove waste from the body.
“If you have PKD, the dogma is that it’s a genetic disease,” Weimbs said. “And no matter what you do, you go into kidney failure and diet doesn’t make any difference, which is unfortunately what most patients are told to this day.”
This prevailing belief was what the Weimbs Lab and its collaborators from various research institutions in Germany wanted to challenge with their test. Sixty-six PKD patients were recruited by the German research team led by medical researcher Dr. fasting every month and a third group who observed a low-carb, high-fat ketogenic diet. Patients were followed closely with blood tests and MRI scans.
At the end of the three-month trial period, the researchers found that while the control group showed the expected increase in kidney size, the kidneys of the ketogenic diet patients stopped growing and appeared to show a tendency to shrink somewhat, although the researchers pointed out that the shrinkage during the 90-day trial period failed to meet statistical significance.
The most impressive evidence came in the form of measurably improved kidney function in ketogenic diet patients, which was statistically significant.
“Much to everyone’s surprise, kidney function actually improved with the ketogenic diet,” Wiembs said. It’s not something you’d expect, he added, if PKD was really something that could only get worse over time. “And that was a hard result of statistical significance.”
Kidney function was measured by the concentration of a protein called cystatin C — higher than normal concentrations of this protein in the blood indicate a failing filtration system, a symptom that worsened in the control group.
The ketogenic diet was rated “very doable” by patients during the study, indicating strong motivation and ability to control their condition through dietary choices alone. “Doctors often assume their patients can’t stick to a diet anyway, so they don’t even try. Clearly, that’s not true. People with PKD are highly motivated to do something about their condition,” he said.
Different kinds of keto
However, according to Weimbs, there is no one-size-fits-all keto diet. To get the most out of their diet, PKD patients should consult with their doctors and nutritionists as they move away from the usual standard carbohydrate and sugar diets prevalent in industrialized societies.
“A keto diet is just very low carb,” he pointed out. There are many main applications of this popular diet for weight loss. Although a popular version of the ketogenic diet is heavy on meat, this may not be the best choice for all people with kidney disease. More plant-focused keto diets are also available, such as the Ren.Nu diet developed by Weimbs in collaboration with kidney dietitians specifically for people with PKD and has been available to the public for two years.
More tests to come
These results represent an important milestone for the Weimbs Lab, which for more than two decades has been investigating the cellular mechanisms underlying PKD and other kidney diseases. A serendipitous discovery made by researchers in the lab — kidney cysts had shrunk dramatically in calorie-restricted mouse models — led them to pursue the idea that the fasting response known as ketosis might have some impact on the development of apparent glucose -dependent cysts.
However, as any scientist knows, one needs solid evidence to support any claims of medical benefit to humans. You need clinical trials.
“If you make a discovery in animals but don’t test it in real people, you’ll never know if it makes sense,” Weimbs said. “There will always be doubt and people will say that animal experiments don’t always translate to humans.” Money to fund these trials became a challenge, thanks to the prevailing perception that PKD was inexorable because of its genetic origins.
“And, of course, it’s always difficult to find funding for nutritional interventions, because nobody wants to fund diets; they want to fund drug research,” Weimbs added. Drug companies, which fund most clinical trials, aren’t interested in a diet, he added.
However, Weimbs, along with Dr. Müller, were able to raise additional funding from the PKD Foundation to conduct the clinical trial in Germany.
“Dr. Müller was able to supplement it with some other funding that he had, and we basically designed this trial together based on the animal results,” Weimbs said. “But really the whole trial was run by his team, so they deserve all the credit and they did a fantastic job. They did everything despite the challenges of COVID.”
With these results, Weimbs and his team are looking forward to further clinical trials set to begin next year, one in Toronto and one in Tokyo, to evaluate the effectiveness of a medical food they developed specifically to help PKD patients to reach ketosis. . Called KetoCitra and available through Weimbs Lab’s spinoff company Santa Barbara Nutrients, it’s a formulation of beta-hydroxybutyrate ketone (BHB) produced during fasting, without the other ingredients and fillers that can be found in the versions of BHB at the pharmacy. The studies will include more people — 80 in Toronto and 200 in Tokyo — and follow patients for a year. These trials will investigate the effectiveness of the Ren.Nu plant-focused ketogenic diet in combination with KetoCitra.
“We want to explore the longer-term implications,” Weimbs said. “If this trend of change in kidney volume that we saw in the three-month study is true, we would expect to see a larger and statistically significant difference there as well.