Green Tea Extract?

There are some studies which indicate advantages of Green Tea (Michelle C Venables, Carl J Hulston, Hannah R Cox, Asker E Jeukendrup; Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans, The American Journal of Clinical Nutrition, Volume 87, Issue 3, 1 March 2008, Pages 778–784):

…healthy young men…

Average fat oxidation rates were 17% higher after ingestion of GTE than after ingestion of placebo (0.41 ± 0.03 and 0.35 ± 0.03 g/min, respectively; P < 0.05). Moreover, the contribution of fat oxidation to total energy expenditure was also significantly higher, by a similar percentage, after GTE supplementation. The insulin area under the curve decreased in both the GTE and placebo trials (3612 ± 301 and 4280 ± 309 μIU/dL · 120 min, respectively; P < 0.01), and there was a concomitant increase of 13% in insulin sensitivity.

There are studies which don’t show the same advantages (Br J Nutr. 2009 Mar;101(6):886-94. Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled trial. Brown AL, Lane J, Coverly J, Stocks J, Jackson S, Stephen A, Bluck L, Coward A, Hendrickx H.):

Overweight or obese male subjects, aged 40-65 years…

…epigallocatechin-3-gallate (EGCG) treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo – 0.058 (se 0.75) mmHg; EGCG – 2.68 (se 0.72) mmHg; P = 0.014). No significant change in the other metabolic risk factors was observed.

I wonder if the subjects of the study were part of the difference?


RQ, Hyperinsulinemia and Nighttime Eating

Interesting study done in a metabolic ward (Obesity (Silver Spring). 2011 Feb;19(2):319-23. doi: 10.1038/oby.2010.206. Epub 2010 Sep 23. Higher 24-h respiratory quotient and higher spontaneous physical activity in nighttime eaters. Gluck ME, Venti CA, Salbe AD, Votruba SB, Krakoff J.).

We investigated whether 24-h RQ was higher in individuals who exhibited nighttime eating behavior. Healthy nondiabetic Pima Indians (PI; n = 97, 54 male/43 female) and whites (W; n = 32, 22 male/10 female) were admitted to our Clinical Research Unit. After 3 days of a weight maintaining diet, 24-h energy expenditure (24-h EE), 24-h RQ, rates of carbohydrate (CHOX) and lipid oxidation (LIPOX), and spontaneous physical activity (SPA) were measured in a metabolic chamber whereas volunteers were in energy balance and unable to consume excess calories. Individuals subsequently ate ad libitum from a computerized vending machine for 3 days with amount and timing of food intake recorded. F

ifty-five individuals (36%; 39 PI, 16 W) were NE, who ate between 11 PM and 5 AM on at least one of the 3 days on the vending machines. There were no differences in BMI or percentage body fat between NE and non-NE. After adjusting for age, sex, race, fat-free mass, fat mass, and energy balance, NE had a higher 24-h RQ (P = 0.01), higher CHOX (P = 0.009), and lower LIPOX (P = 0.03) and higher 24-h SPA (P = 0.04) compared to non-NE.

There were no differences in adjusted 24-h EE or sleep RQ between the groups. Individuals with nighttime eating behavior have higher 24-h RQ, higher CHOX and lower LIPOX, a phenotype associated with increased food intake and weight gain.

Night eating and higher RQ (carb oxidation rates). Calorie matched (fed from controlled vending machine). They ate at night and therefore their glycogen levels didn’t drop enough to switch to fat burning. Hyperinsulinemia?


Insulin Resistance – Everything You Want to Know and Probably a Lot More

A great write-up on Insulin Resistance (Clin Biochem Rev. 2005 May; 26(2): 19–39. Insulin and Insulin Resistance. Gisela Wilcox).  It is not an understatement that the paper says:

…More than a century after scientists began to elucidate the role of the pancreas in diabetes, the study of insulin and insulin resistance remain in the forefront of medical research, relevant at all levels from bench to bedside and to public health policy

First some definitions:

Insulin resistance is defined where a normal or elevated insulin level produces an attenuated biological response; classically this refers to impaired sensitivity to insulin mediated glucose disposal.

Compensatory hyperinsulinaemia occurs when pancreatic β cell secretion increases to maintain normal blood glucose levels in the setting of peripheral insulin resistance in muscle and adipose tissue.

Insulin resistance syndrome refers to the cluster of abnormalities and related physical outcomes that occur more commonly in insulin resistant individuals. Given tissue differences in insulin dependence and sensitivity, manifestations of the insulin resistance syndrome are likely to reflect the composite effects of excess insulin and variable resistance to its actions.

Metabolic syndrome represents the clinical diagnostic entity identifying those individuals at high risk with respect to the (cardiovascular) morbidity associated with insulin resistance.

Interesting graphic (major pathways and influences on insulin secretion):

Here’s why Low Carb works so well:

Glucose is the principal stimulus for insulin secretion

Pancreatic β cells secrete 0.25–1.5 units of insulin per hour during the fasting (or basal) state, sufficient to enable glucose insulin-dependent entry into cells. This level prevents uncontrolled hydrolysis of triglycerides and limits gluconeogenesis, thereby maintaining normal fasting blood glucose levels. Basal insulin secretion accounts for over 50% of total 24 hour insulin secretion. … In healthy lean individuals circulating venous (or arterial) fasting insulin concentrations are about 3–15 mIU/L or 18–90 pmol/L

At rest we don’t need glucose for our muscles.

Muscle cells do not rely on glucose (or glycogen) for energy during the basal state, when insulin levels are low. Insulin suppresses protein catabolism while insulin deficiency promotes it, releasing amino acids for gluconeogenesis.

Perhaps of importance to low carb eaters a low level of glucose may produce a lower level of protein synthesis due to its similarity with starvation:

In starvation, protein synthesis is reduced by 50%. hilst data regarding a direct anabolic effect of insulin are inconsistent, it is clearly permissive, modulating the phosphorylation status of intermediates in the protein synthetic pathway.

In insulin resistance, muscle glycogen synthesis is impaired

We get fatter via:

Intracellular glucose transport into adipocytes in the postprandial state is insulin-dependent via GLUT 4; it is estimated that adipose tissue accounts for about 10% of insulin stimulated whole body glucose uptake.

As relates to low carb diets:

Insulin stimulates glucose uptake, promotes lipogenesis while suppressing lipolysis, and hence free fatty acid flux into the bloodstream.

As adipocytes are not dependent on glucose in the basal state, intracellular energy may be supplied by fatty acid oxidation in insulin-deficient states, whilst liberating free fatty acids into the circulation for direct utilization by other organs e.g. the heart, or in the liver where they are converted to ketone bodies.

Ketone bodies provide an alternative energy substrate for the brain during prolonged starvation.


…glucose uptake into the liver is not insulin-dependent

Another interesting section:

Whilst in insulin deficiency, e.g. starvation, these processes are more uniformly affected, this is not necessarily the case with insulin resistance. Compensatory hyperinsulinaemia, differential insulin resistance and differential tissue requirements may dissociate these processes. Resistance to insulin’s metabolic effects results in increased glucose output via increased gluconeogenesis (as in starvation), however, unlike starvation, compensatory hyperinsulinaemia depresses SHBG production and promotes insulin’s mitogenic effects. Alterations in lipoprotein metabolism represent a major hepatic manifestation of insulin resistance. Increased free fatty acid delivery, and reduced VLDL catabolism by insulin resistant adipocytes, results in increased hepatic triglyceride content and VLDL secretion. Hepatic synthesis of C-reactive protein, fibrinogen and PAI-1 is induced in response to adipocyte-derived pro-inflammatory cytokines such as TNFα and IL-6. Insulin may also increase factor VII gene expression.

Other factoids:

The insulin resistance syndrome describes the cluster of abnormalities which occur more frequently in insulin resistant individuals. These include glucose intolerance, dyslipidaemia, endothelial dysfunction and elevated procoagulant factors, haemodynamic changes, elevated inflammatory markers, abnormal uric acid metabolism, increased ovarian testosterone secretion and sleep-disordered breathing. Clinical syndromes associated with insulin resistance include type 2 diabetes, cardiovascular disease, essential hypertension, polycystic ovary syndrome, non-alcoholic fatty liver disease, certain forms of cancer and sleep apnoea.

Good write-up on Diabetes:

Compensatory hyperinsulinaemia develops initially, but the first phase of insulin secretion is lost early in the disorder. Additional environmental and physiological stresses such as pregnancy, weight gain, physical inactivity and medications may worsen the insulin resistance. As the β cells fail to compensate for the prevailing insulin resistance, impaired glucose tolerance and diabetes develops. As glucose levels rise, β cell function deteriorates further, with diminishing sensitivity to glucose and worsening hyperglycaemia. The pancreatic islet cell mass is reported to be reduced in size in diabetic patients; humoral and endocrine factors may be important in maintaining islet cell mass



Insulin Levels in the Obese

Another interesting study on the levels of fasting Insulin in obese vs non-obese people (J Clin Invest. 1988 Feb; 81(2): 442–448. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. K S Polonsky, B D Given, and E Van Cauter). Here’s the differences in Insulin levels.

The obese have a much higher basal (background) level.

Insulin secretion rates were consistently elevated in the obese subjects under basal conditions (11.6 +/- 1.2 vs. 5.4 +/- 0.5 nmol/h)

The obese also had a much higher Insulin response.

…in the 4 h after breakfast (139 +/- 15 vs. 63 +/- 5 nmol/4 h, P less than 0.001), lunch (152 +/- 16 vs. 67 +/- 5 nmol/4 h, P less than 0.001), and dinner (145 +/- 18 vs. 65 +/- 6 nmol/4 h, P less than 0.001)…

When Insulin is high it pushes fat and glucose into cells. In the obese it takes more Insulin to push the fat into cells than it does in the normal.

When Insulin is low it allows fat to be mobilized from fat cells.

So what happens when you put a person on Insulin? They get fatter. And they have a harder time losing fat.

If you remove carbohydrates from the diet the Insulin levels drop. After a couple of weeks the basal Insulin levels drops to a level comparable to a normal person.


Obesity and Insulin Resistance

Here’s an interesting paper on the role of obesity in insulin resistance (J Clin Invest. 2000;106(4):473-481. Obesity and insulin resistance. Barbara B. Kahn, Jeffrey S. Flier.) Here’s one of the interesting figures from that paper which shows storage and mobilization (freeing) of fat from fat cells (adipocytes).

In this graphic, fat gets stored from glucose or fat in the diet. Fat in the diet gets shuttled through the liver. Insulin is the key element in the storage and mobilization of fat. That’s the core to the idea that leaning out the liver will reverse diabetes.

At the base of any strategy is lowering Insulin levels.

From (Nutrients. 2013 Jun; 5(6): 2019–2027. Body Fat Distribution and Insulin Resistance. Pavankumar Patel* and Nicola Abate.):

Insulin resistance is an underlying key pathophysiologic process in the development of cardio-metabolic disorders among obese individuals. Insulin resistance leads to development of an atherogenic dyslipidemic profile, and prothrombotic and proinflammatory states.

Dyslipidemia in insulin resistant individuals is characterized by elevated triglycerides, apolipoprotein B, small dense low density lipoprotein (LDL) particles, and reduced high density lipoprotein (HDL) concentration and smaller HDL particle size. Insulin resistance also leads to elevated blood pressure and glucose intolerance, which in the presence of genetic and environmental factors, can progress to hypertension and type 2 diabetes mellitus


Insulin Resistance and Diet Type

Here’s an interesting pilot (small) study (Obesity 2016:24, 79–86. Weight Loss on Low-Fat vs. Low-Carbohydrate Diets by Insulin Resistance Status Among Overweight Adults and Adults With Obesity: A Randomized Pilot Trial. Christopher D. Gardner, Lisa C. Offringa, Jennifer C. Hartle, Kris Kapphahn, and Rise Cherin.).

The study compared two dimensions: high/low insulin resistance against high/low carb diets. This meant that four groups of people were studied.  The study concluded that weight loss was comparable between all four groups.

Substantial weight loss was achieved overall, but a significant diet vs Insulin Resistance status interaction was not observed. Opportunity to detect differential response may have been limited by the focus on high diet quality for both diet groups and sample size.

The Low Carb group ended up eating 22% of calories from carbohydrates which is not ketogenic levels. There were significant improvements in most of the cardiovascular markers in favor of the Low Carb/Insulin Resistant group (See Table 3).


Zone Diet Paradigm Difference

The ketogenic diet (for the control/reversal of diabetes) is based on the notion that excessive consumption of carbs leads to Insulin Resistance which is the basis of diabetes. Thus, reducing carbohydrates results in a reversal of diabetes because it improves Insulin Sensitivity (ie, it decreases Insulin Resistance).

The author of the Zone Diet agrees that Insulin Resistance is the core issue in weight loss but disagrees with the cause of Insulin Resistance. From (Insulin Resistance and Weight Loss. Dr. Sears. Apr 6, 2018):

It is constantly elevated insulin levels that makes you gain weight, and keep the weight on. The reason is that if the muscle cells are not taking in enough glucose from the blood, the increased insulin levels drive that glucose into the fat cells instead and that accelerates the storage of dietary excess calories as stored fat. This makes you gain weight. Furthermore, these increased insulin levels prevent your fat cells from releasing stored fat to be used as energy for the body. This keeps the weight on.

Agreed. And, that is the premise of the ketogenic diet as well.

Insulin is a hormone that helps regulate the amount of glucose, a breakdown product of carbohydrates, in our blood required for optimal brain function as well controlling enzyme activities, gene expression and the distribution and storage of energy.

Here Dr Sears shows a common but fundamental misconception about the role of dietary carbohydrates. Carbohydrates are not required to produce glucose. The liver can produce more than enough glucose in the liver though Gluconeogenesis (GNG) from other substrates such as body fat. If dietary carbohydrates were required then the blood sugar during fasting would not level out – which it does.

To be fair, I assume Dr Sears knows better.

So What’s the Difference of Keto vs Zone?

The Zone Diet has a different diagnosis to the cause of Insulin Resistance. With the Zone Diet, it’s not carb intolerance that is postulated to be the core issue, it’s inflammation that causes Insulin Resistance. From Dr Sears:

insulin resistance … is caused by increased cellular inflammation.

There are several factors that play a role in insulin resistance, but cellular inflammation is the biggest culprit.

Dr Sears explains his view of cellular inflammation in this article (What is Cellular Inflammation? Dr. Barry Sears. Jan 10, 2012). In the article he cites quite a few papers but many of these are his own papers.

Back to the original article:

Cellular inflammation results from an imbalance of two key fatty acids in our blood, Arachidonic Acid (AA) and Eicosapentaenoic Acid (EPA). When the levels of arachidonic acid are in excess it leads to the generation of hormones known to be pro-inflammatory. This inflammation makes it difficult for insulin to communicate with our cells in the liver, muscle, and adipose tissue.

Let’s check out Dr. Sears assertions. From (Essential fatty acids in health and chronic disease. Artemis P Simopoulos. The American Journal of Clinical Nutrition, Volume 70, Issue 3, 1 September 1999, Pages 560s–569s):

Human beings evolved consuming a diet that contained about equal amounts of n−3 and n−6 essential fatty acids. Over the past 100–150 y there has been an enormous increase in the consumption of n−6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds, cottonseed, and soybeans.

n−3 Fatty acids, however, have antiinflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of n−3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type 2 diabetes, and, in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn disease, and chronic obstructive pulmonary disease.

Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, α-linolenic acid, found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the human body to EPA and DHA and by itself may have beneficial effects in health and in the control of chronic diseases.

This particular paper, at least, supports Dr Sears’ position on dietary causes other than high carbohydrates being the source of hyperinsulinemia and Type 2 Diabetes. However, one of the referenced papers sheds light on this as a diabetic therapy.

In a randomized, double-blind, placebo-controlled, crossover trial, patients with type 2 diabetes consumed 6 g n−3 fatty acids (EPA and DHA)/d for 6 mo in addition to their usual oral therapy (14). Fasting serum glucose concentrations increased by 11% during the n−3 fatty acid phase and by 8% during the placebo phase (olive oil), showing a nonsignificant net increase of 3%.

Similarly, there was no significant change in glycated hemoglobin concentrations.

However, fasting triacylglycerol concentrations decreased by 43%, which is a highly significant change. This study is the largest and longest reported placebo-controlled trial of the effect of n−3 fatty acids on type 2 diabetes. It showed convincingly that n−3 fatty acid intake, along with oral therapy for diabetes, can lower triacylglycerol concentrations with no adverse effects on glycemic control.

This was more than enough time for an improvement in HbA1C values, but there was no improvement on blood sugar control. There was an improvement in triaglycerol concentrations (Connor WE, Prince MJ, Ullmann D, et al. The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Ann N Y Acad Sci 1993;683:337–40.)

Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet.

Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change.

The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients.

Here’s a metastudy that looked at 26 studies on the subject (Fish Oil and Glycemic Control in Diabetes. DIABETES CARE, VOLUME 21, NUMBER 4, APRIL 1998. Frieberg,

The use of fish oil has no adverse affects on HbA1 c in diabetic subjects and lowers triglyceride levels effectively by almost 30%. However, this may be accompanied by a slight increase in LDL cholesterol concentration. Fish oil may be useful in treating dyslipidemia in diabetes.

Fish oil administration resulted in a tendency for fasting blood glucose levels to be higher in NIDDM subjects (0.43 mmol/l [95% CI, 0.00–0.87], P = 0.06) and to be significantly lower in IDDM patients (-1 . 86 mmol/l [95% CI, -3.1 to -0.61], P = 0.05). This difference in fasting blood glucose responses to fish oil between NIDDM and IDDM subjects was significant (P = 0.01).

Fish oil consumption lowered serum triglycerides significantly by 25–30% in both types of subjects and resulted in a slight but significant increase in LDL cholesterol levels in NIDDM subjects only.

So it sounds to me like fish oil has no real/consistent effect on blood sugars and they raise LDL levels a bit. They do lower serum triglycerides which is a good thing. Makes me glad I take them.

So Dr Sears’ argument that Diabetes is ultimately caused by incorrect amounts of Omega-3 to Omega-6 ratios is demonstrably refuted by the actual evidence that supplementation doesn’t improve HbA1C. This may also be the reason that people on the Zone diet don’t get cured from Diabetes – except to the extent that their weight drops.


Insulin Load in Diabetics

High Fasting Insulin levels are the lock that prevents a person from using body fat.

Of the three macros (fat, carbs and protein) only carbs have a significant impact on blood sugar and as a result can raise insulin levels. Clearly, if you reduce the carb load you also reduce the area under the curve for Insulin while digesting food. But does lower carb consumption at meals impact fasting (basal) insulin levels?

From (Insulin Response to Glucose in Diabetic and Nondiabetic Subjects. John D. Bagdade, Edwin L. Bierman, and Daniel Porte Jr. Journal of Clinical Investigation. October 1, 1967):

Obesity, but not diabetes, was associated with an elevation of this basal insulin level.

Thus obesity predicted with the magnitude of the insulin response to glucose ingestion.

Thus increasing degrees of carbohydrate intolerance were associated with decreasing insulin responses. Elevated levels of insulin, in both the basal state and in response to glucose, were related to obesity.

More specifically from the text of the study:

Fasting insulin levels of obese subjects (36 uU +/- 17.6) were significantly higher (P < 0.001) than those of the thin subjects (14 uU +/- 4.8). … Thus the degree of obesity, and not the carbohydrate intolerance, was associated with the insulin levels maintained after an overnight fast.

So it’s not so much the carb intolerance but the obesity itself which raised fasting insulin levels. The next observation was:

…there was a highly significant linear correlation between fasting insulin and insulin response to glucose in both nondiabetic and diabetic subjects. This demonstrates a tendency for subjects with higher fasting levels to demonstrate greater insulin responses to glucose.

The initial insulin response to glucose in diabetics is attenuated and the total insulin response is also less at the same weight. However, obese diabetics produce a significantly larger amount of Insulin than thin diabetics or non-diabetics.

It is interesting how much of a driving force that obesity is. Fasting Insulin levels were not related to a diabetic response to glucose as much as whether or not a person is obese.

No matter what the cause, the prescription is the same – weight loss.

Explains Some Low Carb Folks

This does explain people who are on low carb and still have high fasting levels of Insulin and are obese. Low carb alone won’t solve the fasting levels of Insulin but loss of weight will.

This goes a long way to explaining why some low carb individuals can’t seem to lose much weight and are still obese even after a long time on Low Carb (Two Keto Dudes, Jimmy Moore come to mind). One of the Two Keto Dudes Richard (I believe it was) commented that he has a high fasting insulin even after years on keto.


Hypertension and Hyper-Insulinemia

From this study (J Clin Invest. 1985 Mar; 75(3): 809–817. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. M Modan, H Halkin, S Almog, A Lusky, A Eshkol, M Shefi, A Shitrit, and Z Fuchs):

83.4% of the hypertensives were either glucose-intolerant or obese–both established insulin-resistant conditions.

We conclude that insulin resistance and/or hyperinsulinemia
(a) are present in the majority of hypertensives, (b) constitute
a common pathophysiologic feature of obesity, glucose intolerance, and hypertension, possibly explaining their ubiquitous association, and (c) may be linked to the increased peripheral vascular resistance of hypertension, which is putatively related to elevated intracellular sodium concentration.

Hypertension? Cause may be elevated Insulin levels.


Objections to the Keto Diet – Part 4 – Long Term Consequences Are Unknown

One of the frequently repeated criticisms by dietitians of the ketogenic diet is the claim that long term consequences of the diet are unknown. This claim needs to be compared against other diets. The other question is what sort of consequences are being compared against. Also, how long is “long-term”?

Studies on the Long Term Consequences

It is difficult and expensive to do randomized control trials of diets on a long term basis. This gets particularly difficult to do this in a metabolic ward. What other diet has passed this hurdle?

The truth is there have been long term studies of captive populations under controlled conditions.

This 2004 study was a 24-week study which showed favorable results for the ketogenic diet (Exp Clin Cardiol. 2004 Fall; 9(3): 200–205. Long-term effects of a ketogenic diet in obese patients. Hussein M Dashti, MD PhD FICS FACS, Thazhumpal C Mathew, MSc PhD FRCPath, Talib Hussein, MB ChB, Sami K Asfar, MB ChB MD FRCSEd FACS, Abdulla Behbahani, MB ChB FRCS FACSI PhD FICS FACS, Mousa A Khoursheed, MB ChB FRCS FICS, Hilal M Al-Sayer, MD PhD FICS FACS, Yousef Y Bo-Abbas, MD FRCPC, and Naji S Al-Zaid, BSc PhD). From the results:

The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.

There could be some currently unknown test that the ketogenic diet might be demonstrated to be negative but no study has shown a negative effect.

Another [small] patient population (n=3) has been studied for five years. This population has aglucose transporter 1 deficiency syndrome (GLUT-1 DS) that is only treatable with a ketogenic diet.  That study which focused on bone density and body composition is described in this study (Nutrition, 2014, 30(6), 726-728. Long-term effects of a ketogenic diet on body composition and bone mineralization in GLUT-1 deficiency syndrome: a case series. Bertoli, S., Trentani, C., Ferraris, C., De Giorgis, V., Veggiotti, P., & Tagliabue, A.). From the results:

Our data suggest that maintaining a Ketogenic Diet for more than 5 years does not pose any major negative effects on body composition, bone mineral content, and bone mineral density in adults with GLUT-1 DS…

Let’s take this up a notch. Where’s the proof that any other diet has similar safety? The low fat switch was made with zero evidence and all of the evidence in the meanwhile has shown low-fat was a bad choice.

A recent, longer study of the same sort of patients (GLUT-1 deficient patients) was done (Clin Nutr. 2017 Nov 11. 10 patients, 10 years – Long term follow-up of cardiovascular risk factors in Glut1 deficiency treated with ketogenic diet therapies: A prospective, multicenter case series. Heussinger N, Della Marina A, Beyerlein A, Leiendecker B, Hermann-Alves S, Dalla Pozza R, Klepper J.). From the results:

Baseline and 10 year follow-up investigations were available for 10 individuals with Glut1D on KDT. After two years on KDT BMI increased significantly, while total cholesterol, HDL-cholesterol, and LDL-cholesterol decreased. Within 3-5 years on KDT these differences disappeared, and after 10 years blood lipid parameters reflected the situation at initiation of KDT. Prior to KDT one child had dyslipidaemia, but no child after 10 years on KDT. No significant differences were observed with respect to BMI SDS (p = 0.26), CIMT (p = 0.63) or systolic and diastolic blood pressure (SDS p = 0.11 and p = 0.37, respectively) in Glut1D children treated with KDT for at least 10 years compared to healthy controls.

Children with seizures have been treated with the ketogenic diet since the 1920’s.

This is a very interesting study with a shorter term but surprisingly good results for the ketogenic diet (Nutr Metab (Lond). 2018; 15: 18. Resting metabolic rate of obese patients under very low calorie ketogenic diet.
Diego Gomez-Arbelaez, Ana B. Crujeiras, Ana I. Castro, Miguel A. Martinez-Olmos, Ana Canton, Lucia Ordoñez-Mayan, Ignacio Sajoux, Cristobal Galban, Diego Bellido, and Felipe F. Casanueva). The study results were:

The rapid and sustained weight and Fat Mass loss induced by VLCK-diet in obese subjects did not induce the expected reduction in Resting Metabolic Rate, probably due to the preservation of lean mass.

Over 250 medical centers worldwide offer ketogenic diets to children with epilepsy. This study looked at five years (Epilepsy Behav. 2016 May;58:61-8. Establishing an Adult Epilepsy Diet Center: Experience, efficacy and challenges. Cervenka MC, Henry BJ, Felton EA, Patton K, Kossoff EH.)

This study, the largest series of adults with epilepsy treated with ketogenic diet therapies to date, provides evidence that ketogenic diets may be feasible, effective, and safe long-term in adults…