We all know that it’s time for mainstream science to investigate—rigorously and on a large scale—whether eating a particular diet can help reduce or reverse chronic disease. While we have growing evidence on the Mediterranean diet, we know little about the molecular benefits and risks of eating certain foods, not eating specific macronutrients, or other emerging condition-based protocols that involve nutritional modulation, particularly related to insulin and glucose signaling. Virta’s pioneering study of the ketogenic diet in type 2 diabetics, published last year by Sarah Hallberg, MD and team, is the first evidence-based treatment to reverse diabetes safely without medication or surgery.1 Their method combined an app, Bluetooth weight scales that participants used at home, and innovative tech support with health coaches. Here is the evidence of improved metabolic flexibility: within one year, patients lost weight (30 pounds, compared to none in the usual care group); decreased their blood pressure; 100 percent stopped their sulfonylureas, 94% had insulin either reduced or eliminated, hemoglobin A1c dropped by 1.3%; insulin resistance (HOMA-IR) declined by 55%; and inflammation, as measured by hsCRP, dropped 39%.
We can all learn a lot from what Virta has accomplished, and importantly, apply the teachings to our clinics. That’s why we want to share the details of Virta’s discoveries with you. In this article, we provide the top 4 insights from the Virta trial. Let’s hope Virta is the first of many studies demonstrating whether specific diets or protocols can improve our health.
Introduction
For many practitioners, type 2 diabetes (T2D) and obesity are the most pervasive and challenging problems confronted daily. Despite decades of effort by both patients and physicians, these diseases are increasing in prevalence.2 Obesity-associated diabetes has become an epidemic in the developed world where food is plentiful and exercise is optional. Although there is agreement that lifestyle changes affecting dietary habits and physical activity are critical for weight control and considered a first-line therapy for controlling blood sugar, the ideal approach is still under debate.
The ketogenic diet (aka “keto”) approach has recently surged in popularity, and many patients with T2D are consulting their doctors with questions regarding weight management and glycemic control using this therapeutic approach. It can be easy to dismiss the keto diet as yet another trendy diet because it is a top google search term, perhaps unbalanced and unhealthy—particularly what is known as lazy keto. The existing literature on keto actually shows it to be effective for weight loss efforts and more effective than a low-fat diet over 12 months;3 however, concerns regarding the use of the keto diet as a treatment tool for diabetes may be attributed to the lack of data on its long-term efficacy, compliance, and sustainability. Fortunately, the Virta Health study arrived just in time to fill this important gap.
Enter: The Virta study
The Virta Health Study is a landmark clinical trial that assessed the long-term effectiveness and safety of a continuous care intervention (CCI) model using a nutritional ketogenic diet compared to usual care (UC) for the management of T2D.1 This study included 349 adults with T2D and overweight/obesity (262 in CCI; 87 in UC); nearly 90% of participants had been prescribed T2D medications.
For the CCI model,1 participants were provided individualized nutrition recommendations to achieve and maintain nutritional ketosis (0.5-3.0 mM blood β-hydroxybutyrate [βHB]). A web-based app was provided for monitoring of body weight, blood glucose, and blood βHB level. Access was provided to a remote care team consisting of a health coach and medical provider for keto diet advice and T2D medication management. Social support was provided via an online peer community.
Primary endpoints included glycosylated hemoglobin (HbA1c), body weight, and medication prescription at the end of each year. Secondary outcomes included fasting serum glucose and insulin, homeostatic model assessment of insulin resistance (HOMA-IR), blood lipids and lipoproteins, liver and kidney function markers, and high-sensitivity C-reactive protein.1
Four major insights were gained from the Virta study, namely:
INSIGHT #1: A ketogenic lifestyle approach is safe and effective for managing type 2 diabetes
The Virta study revealed that patients following a keto diet in the CCI experienced a significant reduction in HbA1c (7.6 to 6.3%), lost an average of 12% body weight, and reduced or stopped diabetes medication use within 70 days and sustained outcomes after 1 year.1
The retention rate in the study was impressive: 90.8%, 83%, and 74% retention at 11 weeks, 1 year, and 2 years, respectively.1,4,5 The ketogenic lifestyle employed by the Virta model does not explicitly prescribe caloric restriction and therefore, may have been easier to follow and sustain than low-calorie restricted diets.
One of the strategic benefits of the keto diet is improved satiety, which often results in overall decreased daily energy intake, further helping patients achieve weight loss while simultaneously controlling blood sugars.1 On average, a 10% weight loss was observed at the end of 2 years in the CCI patients, whereas no weight change was observed in the UC group.5
It’s important to point out that the Virta study included patients prescribed insulin and with long-standing disease (average 7-9 years since T2D diagnosis).3 These characteristics are often exclusion criteria in other low-carbohydrate studies, but positive changes in medication use is a highly relevant and impactful clinical outcome.6,7 For participants using T2D medications:
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40% of CCI participants who began the study with insulin prescriptions (average dose of 64.2 units) eliminated the medication, while the remaining 60% of insulin users reduced their daily dosage from 105.2 to 53.8 units.1
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Glycemic control remained improved at 2 years among the CCI group and was lower than the UC group.5
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The 2-year T2D remission rate in the CCI (17.6%) was higher than that achieved through intensive lifestyle intervention in the Look AHEAD trial (9.2%).5,8
Since cardiovascular disease (CVD) accounts for 44% of the mortality among those with T2D, it is critical that dietary and lifestyle interventions must positively impact CVD outcomes in patients with T2D.9 It is a common misconception that saturated fats from the diet increase blood levels of saturated fats.10,11 The 2015-2020 US Dietary Guidelines suggest that fats should be limited to less than 30% of total calories and saturated fats limited to less than 10% of total calories.12 The ketogenic lifestyle requires a major paradigm shift from these guidelines. In the past, low-carbohydrate diets have consisted of very highly saturated fats (think bacon) and have resulted in negative outcomes including those related to CVD risk factors.13
In contrast, the low-carbohydrate diet described in the Virta study is a well-formulated approach—including 70% fat from mostly monounsaturated, omega-3, and healthy saturated (e.g., coconut oil, medium-chain triglyceride [MCT] oil) fatty acid sources; 20% protein; and 10% carbohydrates.1 Assessments of CVD risk factors in the Virta study netted a significant reduction in blood pressure in the CCI group, with an overall reduction in antihypertensive medication and diuretic use.14 Further, significant changes in cardiovascular biomarkers at 1 year were demonstrated, including a 24.4% reduction in triglycerides, 9.9% increase in LDL-C (but this change appeared limited to the large LDL subfraction), 18.1% increase in HDL-C, and 9.8% increase in apolipoprotein A1 (apoA1).14
Also noteworthy: No adverse events nor discontinuation were reported related to the ketogenic intervention. There were no reports of metabolic acidosis nor severe hypoglycemia requiring assistance, and little or no change in kidney and thyroid function.5
INSIGHT #2: The goal of a ketogenic lifestyle is to build metabolic flexibility
Metabolic flexibility is the ability to respond or adapt to conditional changes in metabolic demand.15 The insulin resistance pathophysiology exhibited with T2D results in reduced metabolic flexibility of mechanisms involved in fuel selection between glucose and fatty acids.15
When the body adapts to the keto diet well (i.e., metabolically flexible), circulating blood βHB levels are no longer as high (but still near 0.5 mM). This phenomenon is an indication that cells in the body are utilizing ketone bodies more efficiently, leading to lower ketone body levels circulating in the blood.1 To that end: The Virta study showed that βHB spiked early as expected, indicating nutritional ketosis, and then stayed relatively stable and finally dropped steadily and gradually, even slightly below the guideline defined level for nutritional ketosis (> 0.5 mM blood βHB).1
The keto diet is the only diet with a specific surrogate biomarker—βHB. This allows the healthcare team to assess and improve metabolic flexibility by individualizing nutrition recommendations to sustain nutritional ketosis by titrating carbohydrate and protein intake to the patient’s individual tolerance.16 The 70:20:10 principle with 50 grams/day of carbohydrates max is only the starting point for personalization, not a strict rule. In fact, the insulin resistance that is typical of T2D may require total dietary carbohydrates to be more severely restricted, to < 30 g/day initially.4
With biometric feedback and telemedicine support, the keto diet can easily be modified to accommodate diverse lifestyles or needs, such as vegetarian/vegan or lactose intolerance. Once a patient is metabolically healthier and is comfortable with the keto diet lifestyle, the diet can be flexible to accommodate for days that aren’t so strict. Ketosis can be achieved again quickly with continued favorable health outcomes, enabling adherence to the program in the long term.
INSIGHT #3: The ketogenic lifestyle can be safely followed with ongoing practitioner guidance
One reason the CCI in the Virta study was so superior to the UC was that the study employed multiple tools to keep patients under ongoing monitoring and supervision:1
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βHB and glucose were monitored routinely via fingerstick blood monitoring using a handheld device.
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Anthropometrics were obtained using a cellular-connected body weight scale, and blood pressure cuffs were provided for patients with hypertension.
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A cell phone app was used for biomarker reporting and monitoring.
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Educational content was delivered via weekly onsite or web-based classes.
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The remote care team provided support to each participant through daily tracking of biomarkers and individualized goal setting, problem solving, reinforcement, repetition, encouragement, and relapse prevention.
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Medications were reviewed and managed by the team weekly.
While most clinicians may not have the resources of the Virta study, there are many tools available for both clinicians and patients to facilitate success with a keto diet program using the lessons learned in the Virta study. In fact, Metagenics Institute offers a simple flowchart to help practitioners determine which diet is best suited to each patient’s unique needs.
When a patient with T2D asks if the ketogenic lifestyle is good strategy for managing their diabetes, it is important to first evaluate his or her level of readiness.17 While a keto diet may work for some, it’s not meant for all. Since dietary habits are hard to break, and T2D management takes a great deal of long-term work, a ketogenic approach is best for patients who are highly motivated.17
Prior to starting the keto diet, clinicians should review potential complications and tolerance issues with patients.18 Prime candidates should be consulted on the importance of adherence to the diet and regular monitoring of ketone bodies to reach and maintain nutritional ketosis.17
There are many ways to formulate a highly palatable ketogenic diet using real foods. Clinicians may design their own keto diet plan or select trusted ketogenic lifestyle resources available to ensure patients are choosing foods that are safe, pleasurable, effective, and sustainable.16 Important principles of a well-formulated ketogenic diet that extend beyond simply restricting carbohydrate include:16
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Daily protein intake targeted to a level of 1.5 g/kg of reference (i.e., medium-frame “ideal”) body weight
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Dietary fats incorporated to facilitate satiety: monounsaturated, omega-3, and healthy saturated fatty acids should be emphasized
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3-5 servings of nonstarchy vegetables
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Adequate mineral and fluid intake for the ketogenic state
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Consideration for inclusion of exogenous ketone supplementation
INSIGHT #4: Monitoring is key to success
Blood sugar in patients with T2D can improve quickly when patients eat significantly fewer dietary carbohydrates. The Virta study observed improvements in blood insulin, glucose, and lipids within the first 2-4 weeks following intervention and before significant weight loss was achieved, with most improvements documented in the first 70 days.1 These glycemic changes demand ongoing medicine management by doctors. For the practitioner, this initial startup period is a good time to establish the keto diet lifestyle, help patients get plugged in with educational resources and support groups, and adjust treatment, medication, and diet plan to the patient’s individual biochemistry.
Several commercial ketone tests are available, including urine, blood, and breath monitors. However, utilizing the blood monitor will enable doctors and patients to simultaneously keep track of blood glucose levels, which is critical for managing T2D medications, especially in the first 10 weeks of the diet. This can be accomplished by having patients send daily ketone and glucose updates via text or web-based patient chart to the healthcare team for at least 2 weeks or until the patient has reached nutritional ketosis, and glucose readings and medications have stabilized. There are a number of HIPAA-compliant texting services and telemedicine healthcare partners that can be utilized, allowing integration with clinical systems to enhance the continuous supervision necessary for optimal outcomes.
Tracking weight, glucose, and βHB levels provides the healthcare team with biometric feedback for behavior reinforcement. Teaming up with a nutrition expert to provide individualized diet recommendations, accountability, and monitoring can be an incremental asset to safely support patients on a ketogenic diet.
Conclusions
The ketogenic diet can easily be performed wrong and be rejected as a fad diet. However, the Virta study provides a clinically tested template for success in T2D management. With strategic lifestyle modifications, accountability mechanisms, and medical supervision, sustained improvements and even T2D disease reversal can be achieved. For motivated or curious patients with T2D, it is an intervention worth pursuing. For practitioners taking care of diabetic and perhaps prediabetic patients, it is time to become equipped to offer a ketogenic diet in your practice.
For additional, evidence-based information and resources on the ketogenic diet, visit MetagenicsInstitute.com. For practitioners seeking guidance on selecting a diet best suited to their patient’s needs, Metagenics Institute offers a complimentary, straightforward flowchart.
This information is for educational purposes only. The statements have not been evaluated by the Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent any disease. Consult your physician if you have any question regarding a medical condition
