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Beyond weight loss, ketogenic diet may show promise for diabetes, PCOS

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A ketogenic diet, an eating plan consisting of very low-carbohydrate and high-fat intake, has gone in and out of vogue over the years, with proponents of the diet touting not only potential weight-loss benefits, but promising data for everything from drug-resistant epilepsy in children to diabetes and polycystic ovary syndrome.

An online search for “ketogenic diet” will bombard the consumer with a seemingly endless list of books, blogs and message board links — all extolling the ketosis-inducing diet as a way improve a host of symptoms.

The long-term outcomes for weight loss when adhering to a ketogenic diet remain unclear. Critics of the eating plan stress that it can be difficult to follow beyond a few months. However, research suggests that the diet, by reducing the amount of insulin secreted by the body, can improve blood glucose profile in diabetes and may even improve symptoms of PCOS, including menstrual irregularity and infertility.

“The research suggests that insulin resistance and, maybe, obesity are behind the pathophysiology of the cause of PCOS,” Ula Abed Alwahab, MD, an endocrinologist at Cleveland Clinic, told Endocrine Today. “New research coming out about the ketogenic diet shows that it not only can promote weight loss, but it is insulin sensitizing. That is where the idea came from to combine both and see what happens on a scientific level. Because honestly, if you go on social media nowadays, you find a bunch of things that are not evidence-based on how PCOS improves with a ketogenic diet. We decided to test that.”

Some experts maintain that the short-term benefits of the diet — particularly, an observed improvement in glucose profile — merit consideration for a person with obesity, who is at risk for comorbid conditions such as type 2 diabetes.

Ula Abed Alwahab

“A lot of the proponents of the diet say, why wait for these long-term trials; grab the short-term benefits of the ketogenic diet because obesity and PCOS are both on the rise,” Candida Rebello, PhD, LLB, RD, FTOS, a researcher with the Pennington Biomedical Research Center at Louisiana State University, told Endocrine Today. “The downside is the diet may not be sustainable in the long run. It’s a very high percentage of fat.”

Weight-loss questions

The evidence for weight loss when adhering to a ketogenic diet, studies show, is mixed. In a meta-analysis published in May 2013 in the British Journal of Nutrition, Nassib Bezerra Bueno, PhD, professor in the department of physical education at Federal Rural University of Pernambuco, Brazil, and colleagues assessed whether individuals assigned to a very low-calorie diet with no more than 50 g carbohydrate per day achieve better long-term body weight and CV risk-factor management when compared with individuals assigned to a conventional, low-fat diet (restricted-energy diet with less than 30% of energy from fat) across 13 studies with at least 12 months of follow-up.

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In the overall analysis, only five studies revealed statistically significant results.

The researchers found that individuals assigned to a very low-calorie diet experienced a greater decrease in body weight vs. those assigned to a conventional diet at 1 year (weighted mean difference, –0.91 kg; 95% CI, –1.65 to –0.17), as well as greater improvements in cardiometabolic parameters. However, any between-diet differences did not persist at 24 months, according to the researchers.

“At 12 months, when compared against a low-fat diet, there was a statistically significant decrease in body weight by 0.9 kg, which, though statistically significant, holds very little clinical relevance,” Rebello said. “In people with a BMI between 30 and 40 kg/m², a 2-lb weight loss doesn’t make much difference. In the long run, the ketogenic diet is as good or, maybe, slightly better than a conventional diet. We don’t really know.”

Glucose profile improvements

When it comes to blood glucose management, data regarding a ketogenic diet for the short term are unequivocal, Rebello said.

“Because you are eating less carbs, you’re addressing the most salient feature of diabetes or even PCOS,” Rebello said. “But, these benefits are in the short term. What can happen in the long term is purely conjecture.”

That answer, Rebello said, will require controlled, expensive studies.

Candida Rebello

“It’s 20 to 50 g of carbohydrates, which means most of it has to come from fat,” Rebello said. “You cannot have a very high amount of protein in it because some protein can convert to glucose. Fat, for the most part, does not convert to glucose.”

Promising results

Some researchers are working with a modified version of a ketogenic diet and are reporting surprising findings, although the cohorts remain small.

In a case series analysis published in the September/October issue of Endocrine Practice, Abed Alwahab and colleagues reported on data from four women aged 24 to 29 years diagnosed with PCOS who were trying to conceive while following a ketogenic diet (BMI, 30.75-42.46 kg/m²; duration of infertility, 1-4.5 years). The women attended monthly shared medical appointments for 6 months, where they were assessed for weight-loss progression, menstrual regularity and ovulation. Researchers assigned the women to a maximum daily carbohydrate intake of 20 g, fat intake up to 50 g and protein intake of about 1.5 g for each 1 kg of ideal body weight. Researchers also prescribed 500 mg metformin twice daily if women were not already taking the medication.

At 6 months, the four women lost between 19 lb and 36 lb and resumed regular menstruation shortly after initiating the diet. Additionally, two of the women were able to conceive spontaneously without ovulation induction, according to the case report.

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The researchers now have 1-year data from 16 women who were presented at the Cleveland Clinic 23rd Annual Diabetes Day, a CME-certified educational symposium. The results, Abed Alwahab said, were similar to the findings in the case series, and the study is ongoing.

“Our results, so far, are promising,” Abed Alwahab said. “Yes, there is an improvement in the symptoms of PCOS, and perhaps also in fertility problems that many patients with PCOS have. What astonished me is how quickly symptoms improved for these women. Even before any significant weight loss, these women were able to get their periods back.”

Exercise caution

Rebello and Abed Alwahab said a person should not initiate a ketogenic diet before consulting a medical professional, especially when the person has an underlying condition like diabetes or PCOS.

“It has to be a diet that is monitored,” Rebello said. “These patients are on medications. Hypoglycemia is a very real risk. I would tell them that I would monitor your diet, I will monitor your blood glucose levels, and I will counsel you on how to progress with this diet.”

Abed Alwahab agreed.

“I would never recommend anyone doing a ketogenic diet on their own,” Abed Alwahab said. “A person initiating these needs medical monitoring. At the clinic here, we meet every month and we do labs every month to make sure people are doing well and we are not harming the liver or the kidneys.”

At Cleveland Clinic, Abed Alwahab said, the ketogenic diet used is not what a person may find via a cursory Google search.

“Our version of the ketogenic diet is not what is known to people who think it is simply eat as much fat and protein as you like and just omit carbohydrates,” she said. “Our version is a low-carb diet that pushes you into ketosis, but it is not high fat or high protein. It is not putting pressure on your liver or your kidneys. We are giving a small amount of fat and normal amounts of protein on this program and almost no carbohydrates. It’s a modified version of what people think about as the ketogenic diet on social media.”

The diet, she said, is also limited in scope, typically ranging no more than 6 to 12 months.

“You may hear about people who do this diet for years and years, but we don’t have evidence to support whether that is safe or not,” Abed Alwahab said. “We only do it for a set amount of time, ranging from 6 to 12 months, and then we reassess whether we still need to do this diet. Did we achieve our goal? Our goal is always to reduce the comorbidities — the diabetes, the blood pressure, the cholesterol — and to lose the amount of weight that we planned to lose. Then, we move patients to a non-ketogenic, low-carb diet, one that they can stay on forever, we hope.” – by Regina Schaffer

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References:

Alwahab UA, et al. Endocr Pract. 2018;doi:10.4158/ACCR-2018-0026.

Bueno NB, et al. Br J Nutr. 2013;doi:10.1017/s0007114513000548.

For more information:

Ula Abed Alwahab, MD, can be reached at abedalu@ccf.org.

can be reached at abedalu@ccf.org. Candida Rebello, PhD, LLB, RD, FTOS, can be reached at candida.rebello@pbrc.edu.

Disclosures: Abed Alwahab and Rebello report no relevant financial disclosures.