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Viewpoint
July 15, 2019

The Ketogenic Diet for Obesity and Diabetes—Enthusiasm Outpaces Evidence

Author Affiliations
  • 1Division of General Internal Medicine, Department of Medicine, New York University School of Medicine, New York
  • 2Department of Medicine, NYC Health + Hospitals/Bellevue, New York
  • 3Division of Cardiology, Montefiore Health System, Bronx, New York
JAMA Intern Med. Published online July 15, 2019. doi:10.1001/jamainternmed.2019.2633

The ketogenic diet has recently received much attention for its promise of treating obesity and type 2 diabetes. However, the enthusiasm for its potential benefits exceeds the current evidence supporting its use for these conditions. Although the temptation is great to recommend a potentially novel approach for otherwise difficult-to-treat diseases, it is important to remain grounded in our appraisal of the risks, benefits, and applicability of the diet to avoid unnecessary harm and costs to patients.

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    11 Comments for this article
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    Diabetes and Metabolic Syndrome can be reversed on Keto
    Stephen Riggs, MD | MercyOne Waterloo, IA
    I have been in the practice of internal medicine for over 30 years. In all that time I never took anyone off their insulin or rarely reduced their medications unless they had gastric bypass surgery or something as drastic. After implementing the ketogenic diet for the past year I daily am seeing patients come off insulin and reverse their diabetes, correct their hypertension, feel great, reduce inflammation and chronic pain, improve cognitive scores, correct their dyslipidemia, and improve athletic performance. As with most other physicians my nutritional education was poor and I considered it irrelevant. Today, the low carb approach is by far the biggest tool in my toolbox. So I read with disappointment the Viewpoint by Joshi et.al., replaying the old yarn about the "dangers" of the ketogenic diet and lack of evidence. Actually, though not yet mainstream the ketogenic diet has been extensively studied since its development at Mayo in 1921. Over 30 head to head trials confirm that keto is the king of weight loss diets and that nutritional ketosis (not to be confused with DKA) is a natural physiological condition that not only helps fuel the brain, heart, muscle and gut but current research is exploding with evidence that ketones are also signaling molecules that turn on many biologically beneficial pathways that reduce inflammation, lower seizure activity, promote glycogen sparing, increase athletic performance and especially lower insulin resistance and can even reduce or eliminate the need for diabetes medications. There are currently over 30 clinical trials ongoing looking at the ketogenic diet and cancer therapy for its profound metabolic effects. There have been far more studies on the ketogenic diet than either vegetarian, DASH, or the Mediterranean diet. In the words of Duke University researcher Eric Westman "If Keto were a drug it would already have FDA approval."There is no drug that can do what the low carb diet can. There are many medical interventions that we clinicians in the trenches do based solely on what we are told in the literature based on p-values and confidence intervals based on massive population studies; we take it on faith and clinical practice guidelines. Not so with keto. The evidence is so remarkable and patients get better literally right before our eyes. I have had patients that I diagnosed with diabetes over 15 years ago and gradually ramped up their medications including > 100 units of insulin and within 2-3 months most are off insulin and their other meds as well. What drug can do that? In the words of Elliot Joslin (founder of Harvard's Joslin Diabetes Center) before the advent of insulin, the evidence for the low carbohydrate treatment of diabetes is so obvious that "no clinical trials are needed." My experience with hundreds of real patients – patients I have diagnosed and treated for 15, 20 or even 30 years just watching them get sicker and fatter and within months seeing their health rebound and diabetes resolve is hard to ignore. I only hope the medical establishment will catch up to what is being rapidly discovered here "in the trenches." But don't take my word for it. For those interested in the massive amount of evidence for the ketogenic diet I would encourage the Ketogenic Nutrition Course by the ANA (American Nutrition Association) for starters. My own conclusion after doing a deep dive on this over the past year is that this will be standard of care in 10 years. In 30 years, we will look back on the decision to take fat out of our diet as the biggest public health mistake we ever made.
    CONFLICT OF INTEREST: None Reported
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    Ketogenic Diet for Obesity and Diabetes
    David Martin, MD, FACG | Pinehurst Medical Clinic
    Obviously the authors of this paper have not recommended a very low carbohydrate diet (ketogenic diet) to their patients. If they had they would be amazed at how well people do. Patients lose weight, diabetes comes under better control and often they can get off meds. One of my GI techs has lost 90 pounds and no longer meets criteria for polycystic ovary syndrome. In addition to weight loss and improvement in diabetes, reflux symptoms often go away and patients are able to get off PPI's. Fatty liver improves with normalization of transaminases. Joint pains go away. I have a 32 year old male with type 2 diabetes and ulcerative colitis. His ulcerative colitis is well controlled with a biologic, but was having severe joint pain. Wasn't sure whether the biologic was the cause of the joint pain, so switched from Remicade to Humira. Two months later recurrence of joint pain. Switched to Xeljanz. Two weeks later the joint pains much worse. Rheumatology had nothing to offer (NSAIDs would make the colitis worse and steroids would make the diabetes worse. Could potentially try Stelara, but hate to burn through all our biologic options.) With the severe joint pains, finally able to convince him to do the ketogenic diet. Within 3 days he had significantly less joint pain. People also get relief of headaches. IBS-D comes under control. If patients stick with it long enough IBS-C comes under control. I've been using low carb diets, beginning with the specific carbohydrate diet, since 2010. Main difference in SCD and ketogenic diet is emphasis on getting more fat in the diet, which makes it more sustainable-not hungry.
    CONFLICT OF INTEREST: None Reported
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    Agree with the authors and not with the comments given
    Karen Freijer, PhD | Nutrition and Nutrition Economics
    So great that this paper has been published!
    One should be very careful when adapting a food pattern on one's own-especially when it concerns patients! Nutrition is a real profession for which one has to study at least for 4 years!!! It is not something one can learn overnight or by reading a chapter in a book! And nutrition is the basis of our existence and health. It can be very dangerous to just adapt your diet without really knowing what to take into account. Undernutrition in the longer term with all the complications can be the result of
    using a diet without knowing what to take into account. Physicians are the specialists in the field of medicine, but only dietitians/nutritionists are the specialists in the field of nutrition. A physician is also not giving physiotherapy exercises to their patients! So don’t do this for nutrition! You can really harm your patient in the longer term and then it is very hard to reverse the problems that have arisen! Please consult a nutritionist/dietitian when you want to give your patients advice on nutrition!!!
    CONFLICT OF INTEREST: None Reported
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    Authors are misguided
    Jay Wortman, BSc MD CCFP | University of British Columbia
    I personally reversed my T2DM and Mets over 16 yrs ago by adopting a keto diet. I have maintained a 35 lb wt loss and normal HbA1c, lipid profile and blood pressure over that period. I recently had a CAC scan and my score was zero. All this with zero medication. I currently use a keto diet with patients who have any manifestation of insulin resistance plus any who have an inflammatory or CNS condition. I have many success stories. The idea that physicians are not able to safely implement diet change is nonsense. It is important for physicians to understand the specific needs of patients who start a keto diet and to be proactive in managing the inevitable reduction in medications but otherwise it is not rocket science to reduce carbs and encourage a whole food low carb diet.
    CONFLICT OF INTEREST: Member of Scientific Advisory Board, Atkins Nutritionals Inc
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    Please Represent the Full Picture of the Research
    Kelly Sylvester, PhD | University
    There are plenty of studies (many RCTs) available showing the benefits of a low-carbohydrate diet on disease risk. And they are not difficult to locate. To make claims, please represent the full body of evidence, not just one side.
    CONFLICT OF INTEREST: None Reported
    The Ketogenic Diet for Obesity and Diabetes—Evidence Outpaces Enthusiasm
    Angela Stanton, PhD | self employed
    The authors of this paper(1) have ignored critical research that specifically show that neither calorie restriction nor weight loss is the key working force behind the success of the ketogenic diet. A recent article specifically targeted this problem, presented this frequently voiced assumption and proved it incorrect(2).

    In addition, the ketogenic diet leads to the ketogenic metabolic process (ketosis), which is not a fad. People were in ketosis as fetuses(3) in their mother’s womb(4,5), were born in ketosis(6), remained in ketosis through most of nursing, and also all through their childhood nights while sleeping(7).

    The fetus
    in the womb if hardly on a calorie-restricted diet. It is using ketones to build vital organs--such as the brain--made primarily of lipids.

    The ketogenic diet is the best way by which ketosis is achieved and ketosis is clearly a natural human metabolic process that is advantageous for healthy development of an infant and beneficial for healthy body recovery and maintenance for adults.

    1 Joshi, S., Ostfeld, R. J. & McMacken, M. The Ketogenic Diet for Obesity and Diabetes—Enthusiasm Outpaces EvidenceThe Ketogenic Diet for Obesity and DiabetesThe Ketogenic Diet for Obesity and Diabetes. JAMA Internal Medicine, doi:10.1001/jamainternmed.2019.2633 (2019).
    2 Hyde, P. N. et al. Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss. JCI Insight 4, doi:10.1172/jci.insight.128308 (2019).
    3 Herrera, E. & Amusquivar, E. Lipid metabolism in the fetus and the newborn. Diabetes/Metabolism Research and Reviews 16, 202-210, doi:doi:10.1002/1520-7560(200005/06)16:3<202::AID-DMRR116>3.0.CO;2-# (2000).
    4 Paterson, P., Sheath, J., Taft, P. & Wood, C. MATERNAL AND FOETAL KETONE CONCENTRATIONS IN PLASMA AND URINE. The Lancet 289, 862-865, doi:10.1016/S0140-6736(67)91426-2 (1967).
    5 Orczyk-Pawilowicz, M. et al. Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy. PloS one 11, e0152740-e0152740, doi:10.1371/journal.pone.0152740 (2016).
    6 Kimura, R. E. & Warshaw, J. B. Metabolic Adaptations of the Fetus and Newborn. Journal of Pediatric Gastroenterology and Nutrition 2, 12-15 (1983).
    7 Cahill, G. F. Starvation in man. N Engl J Med 282, doi:10.1056/nejm197003052821026 (1970).
    CONFLICT OF INTEREST: None Reported
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    It's all about the context, and the alternatives
    Omer Berner | Ben Gurion University
    There's a significant difference between reviewing this diet as a lifestyle modification for the healthy population or for the diabetic population. Major concerns have been raised about the outcomes of a keto diet, including worsening glucose intolerance (https://www.ncbi.nlm.nih.gov/pubmed/31067015)
    .
    However, in the clinic, one has to think about the pros, cons and alternatives for his specific diabetic patient. In a patient with poor lifestyle and glycemic control, on a lot of medications, proposing a keto diet, despite it's possible negative effects in some aspects, might do more good then bad if indeed the diet enables this specific patient
    to get off his medications and lowering his HbA1C dramatically.
    CONFLICT OF INTEREST: None Reported
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    I too disagree.
    Adeline Louie, MD | retired
    I too disagree with the authors’ assertions. I myself had astronomical lipid values and did not want to be snowed with statins or fibrates. So I undertook a short experiment on myself. I went on a low carb high animal fat diet for 5 weeks. I had no restrictions on calories, and probably took in more calories than normal, as I ate lots of fatty meat. The result: I dropped all my lipid values, especially my triglycerides which decreased close to a 1000 points. And HDL increased. I also sustained a several pound weight loss. All this on no lipid drugs. My A1C and fasting glucose dropped into the normal range too. I will note that I am not obese, and have only a borderline A1C. I have no doubt that diet can reverse what is a modern dietary disease, that of obesity and diabetes Type II.
    CONFLICT OF INTEREST: None Reported
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    Toxicity of Lipophilic Chemicals
    Harold Zeliger, Ph.D. | Zeliger Research & Consulting
    The Keto diet ignores the proven fact that the high fat ingested results in the adsorption of greatly increased quantities of highly toxic lipophiles such as TCDD, PCBs and chlorinated pesticides. These are stored in adipose tissue for decades and slowly, but continually partition into blood and are carried throughout the body.
    CONFLICT OF INTEREST: None Reported
    Still Controversial...after all these years.
    Alexander Anderson, Various | M.D. AndTrade Ltd.
    Not having ever worked in academia, basic research or under large corporate governance but, along with some of the other authors of comments here, in those ubiquitous "trenches", acknowledgement that after more than 7 decades of data and research in this area, that questions still remain as to the basic validity and efficacy of "KETO" is, to put it mildly, rather astonishing. "Meta-analysis of 13 studies lasting longer than a year" along with "a meta-analysis of 32 controlled feeding studies" notwithstanding.

    Some of what this continuing controversy clearly suggests is the following:

    1) What conclusions are drawn depends
    on the information that is arbitrarily select to evaluate;

    2) The size of the frame of effect, conditions and outcomes selected to evaluate in the analysis;

    3) Selection factors that invariably will influence the outcomes of your test subjects and rarely consider genetic influences.

    4) That, like political prejudices, it is unlikely only facts and objective physical realities will influence and inform "objective and scientific" judgments.
    CONFLICT OF INTEREST: None Reported
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    Refreshing Commentary
    John Kaplan, MD | Dr. John's Nutrition Health
    Thank you for listing the various potential side effects of the ketogenic diet. A majority of those attempting the ketogenic diet do not achieve actual or sustained  ketosis. For most, the diet is practiced as another rendition of the low carb diets that have periodically found temporary popularity in the past- Atkins, Paleo, Zone, Southbeach, etc. Thy are all high meat/fat diets. As the article notes, all cause mortality is higher in this group than on a plant- based low fat nutritional plan.
    The epidemic of diabetes is not addressed by the ketogenic diet. Diabetes is not caused by
    carbohydrates. A high animal fat standard American diet diet causes massive amount of intramyocellular lipid concentration primarily in muscle, liver, and pancreatic cells. The fat is stored in places not designed for this heavy lipid load respond by becoming Insulin resistant. Insulin resistance raises intravascular glucose. Hyperglycemia is a symptom of diabetes, not the cause!
    When we calorie restrict patients they lose weight. This is also true for the ketogenic plan. Calorie restriction which also restricts carbohydrates lowers hyperglycemia. The doctor and patient are falsely encouraged by a temporary lowering of blood glucose and HA1C levels. This is at the expense of a health engendering supply of the body's primary energy source from dietary carbohydrate. Insulin resistance on a ketogenic diet proceeds and intensifies on this high animal fat diet. Intensification of risks for cardiovascular disease ( heart disease and stroke), erectile dysfunction, and even dementia also increase on this high meat/fat diet as well.
    Only low fat plant- based diets have demonstrated the ability to reverse cardiovascular disease and diabetes (see studies by Caldwell Essylsten, Dean Ornish, and Neil Barnard)
    The medical profession would greatly benefit by adding nutrition training as a core educational priority in medical schools.
    CONFLICT OF INTEREST: None Reported
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