Ketogenic Diets-good, bad, indifferent? Peter Clifton CSIRO Human Nutrition

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1 Ketogenic Diets-good, bad, indifferent? Peter Clifton CSIRO Human Nutrition

2 Presenter Disclosure Information <Ketogenic Diets-good, bad, indifferent? Disclosure information The following relationships exist related to this presentation: Author A,E: No relationships to disclose Author B, C, D, F: Coauthors of CSIRO Total Well Being Diet books. CSIRO

3 Questions Atkins- very low CHO, high saturated fat, leads to good weight loss at 6 months, sometimes better at 12 months. Does the elevation of HDL and lowering of TG plus lowering of BP, glucose outweigh rise in LDL cholesterol in some? No Atkins endpoint studies. Nurses low CHO diets beneficial under some circumstances CSIRO

4 Meta analysis Nordmann 2006: 5 trials, 447 individuals 6 months, individuals assigned to low-carbohydrate diets had lost more weight than individuals randomized to low-fat diets (weighted mean difference, -3.3 kg; 95% confidence interval [CI], -5.3 to -1.4 kg). Gone at 12 months (weighted mean difference, -1.0 kg; 95% CI, -3.5 to 1.5 kg). There were no differences in blood pressure. Triglyceride and HDLC values changed more favorably in individuals assigned to low-carbohydrate diets:tg weighted mean difference, mmol/l; (95% CI, 0.43 to mmol/l; and for HDL 0.12 mmol/l ( mmol/l) CSIRO

5 Meta analysis Total cholesterol and low-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-fat diets (weighted mean difference in low-density lipoprotein cholesterol after 6 months, 0.14 mmol/l; 95% CI, mmol/l). CSIRO

6 Atkins vs Zone A-Z (Gardner 2007) 311 free-living, BMI kg/m 2 nondiabetic, premenopausal women. Randomised to Atkins (n = 77), Zone (n = 79), LEARN (n = 79), or Ornish (n = 76) diets with weekly instruction for 2 months, then 10- month follow-up Atkins, -4.7 kg Zone, -1.6 kg LEARN, -2.6 kg and Ornish, -2.2 kg Secondary endpoints similar or better no rise in LDL (nor fall in LDL in Ornish very low fat group!) CSIRO

7 Weight Change Relative to Baseline CSIRO Gardner, C. D. et al. JAMA 2007;297:

8 Mean±SE Body Composition Changes (DEXA) baseline weight kg weight loss kg fat mass loss kg lean mass loss kg KET a ±2.4 ±0.6 ±0.5 ±0.4 VLF a ±2.6 ±0.7 ±0.5 ±0.4 HUF b ±2.8 ±0.6 ±0.6 ±0.4 CSIRO

9 Change in Triglycerides 0 diet effect p<0.001 mmol/l KET VLF HUF -0.8 wk0 wk4 wk8 wk12 CSIRO

10 0.4 Change in LDL-C mmol/l diet effect P=0.009 KET VLF HUF wk0 wk4 wk8 wk12 CSIRO

11 CSIRO

12 Introduction: FMD Flow mediated dilatation (FMD) assesses the ability of the blood vessels to respond (dilate) to increases in blood flow Reduced in CVD and DM Whether weight loss per se improves FMD is unclear- may relate to fall in glucose or LDL No tests of Atkins diet

13 Measuring FMD

14 Brachial Artery Ultrasound Ultrasound images of the brachial artery 4.35 mm 4.90 mm 5.33 mm Baseline Flow-mediated Vasodilation NTG-induced Vasodilation

15 Weight stable 10% energy shifts LDL cholesterol 13% higher with saturated fat

16 Aim To assess the effect on markers of endothelial function and CVD risk of a very-low-carbohydrate/high-saturated-fat (20% energy) diet (LC) compared with an isocaloric high-carbohydrate/low-saturated-fat diet (HC). Outcomes FMD and markers of endothelial function (n=70) and CVD risk were measured before and after 8 and 52 weeks of weight loss. Cellular adhesion molecules ICAM-1, VCAM, E&P Selectin Inhibitor & promoter of fibrinolysis Plasminogen activator inhibitor-1 (PAI-1) Tissue plasminogen activator (tpa) Adiponectin Glucose, Insulin, CRP, Lipids, ApoB Subjects year, > 27, < 40 BMIkg/m 2 Presence of markers of the metabolic syndrome (IDF) BMI 33.7±4.1 kg/m2, 50.0±8.3 yr, waist 111.5±10.0 cm, men, 101.5±8.6 cm, women

17 Dietary composition High saturated fat diet 35% protein, 61% fat (20% saturated fat) 4% carbohydrate (LC) Low saturated fat diet 24% protein, 30% fat (<8% saturated fat), 46% carbohydrate (LF) 6000 kj female, 7000 kj male (2-3000kJ energy reduction) Dietary compliance and intake Three days every 2 weeks Food provided ~30% energy requirements Monthly visits for a year

18 Foods Low Carb 6000kJ (LC) 125ml full fat milk70g full fat cheddar cheese 100g (cooked lean protein source) ham, tuna, beef 300g (raw meat) beef, chicken, fish 1 medium (50-55g) egg At least 2.5 cups green vegetables 25g (5tsp) oil/butter 40g raw, unsalted mixed nuts 2 standard alcoholic drinks/week (optional) Low sat Fat 6000kJ (LF) 40g high fibre cereal + 2 slices wholegrain bread (35g) 300ml skim milk, 20g reduced fat cheese (2/7), 200g diet yoghurt (3/7) 2 fruit (150g/serve) cups vegetables 150g raw beef, chicken, pork, lamb (5/7) 150g fish (1/7) 100g bean lentils (1/7) 1 medium potato (3/7) 100g (dry wt) pasta/rice (4/7) 20g raw unsalted nuts (7/7) 50g tinned fish (3/7) 2tsp poly margarine +3 tsp oil 2 standard alcoholic drinks/week

19 Results 12 months weight loss LC HC Body weight (kg) Time (Weeks)

20 Results 12 months 69 subjects remained LC 33 and HC 36 Both groups lost similar amounts of weight LC -14.5±1.7kg, HC -11.5±1.2kg Body fat LC -11.3±1.5kg, HC -9.4±1.2kg FFM more on LC group vs HC group 3.2 ± 0.4kg LC vs -2.3 ± 0.2kg HC (P=0.03 time x diet interaction) BP, glucose, insulin, CRP (no diet effect) TG -0.58±0.11 vs -0.22±0.11mmol/L, LC vs HC P=0.008) HDL-C 0.30±0.07 vs 0.07±0.06mmol/L, P<0.001, LC vs HC LDL-C 0.6±0.2 vs 0.1±0.1mmol/L, LC vs HC P=0.008) apo B (+0.03±0.04 vs -0.06±0.03 g/l, LC vs HC P=0.06).

21 Results 12 months 49 (26 LC, 23 HC) subjects FMD Weight loss was similar in both groups LC -14.9±10.5 kg, HC -11.5±7.4 kg; P=0.20. FMD decreased on LC diet (P<0.05 for diet interaction) 5.70±3.59% to 3.65±2.65%, P=0.001 No change on HC diet HC 5.86±2.54% to 5.51±3.52%; P=0.60 PWV improved in both groups LC 10.74±2.89 m/s to 9.31±1.68 m/s HC 10.98±2.71 m/s to 9.48±2.18 m/s; P=0.001 time (no diet effect) AIx did not change LC 29.25±10.18% to 29.71±10.52%, HC 27.09±10.01% to 28.02±8.21%

22 Overall conclusion FMD deteriorated after 12 months on a high saturated fat diet despite with weight loss LDL-C increased on saturated fat diet Outweighs other benefits of weight loss Other measures of endothelial function-similar improvement except ICAM1- reduced only on Atkins diet. Normally falls with weight loss. Metformin reduces adhesion molecules-fall in IR. Changes in HDL in clinical trials no relation to CVD outcomes after LDL changes accounted for (Riedl 2009).

23 Mean absolute change in FMD at 2 and 6 weeks from LC and LF diets Phillips, S. A. et al. Hypertension 2008;51:

24 Individual subject %FMD at weeks 0 and 6 Phillips, S. A. et al. Hypertension 2008;51:

25 Acknowledgements and thanks Funding NHF/NHMRC Janet Bryson PhD scholarship from ASSO (JK) Clinic and Laboratory staff Study volunteers Co-investigators. Wycherley, Brinkworth, Keogh, Noakes Clinical Centre for Research Excellence in Nutritional Physiology

26 BakerIDI Heart and Diabetes Research Institute CSIRO Food and Nutrition Science Peter Clifton Phone: Thank you Contact Us Phone: or enquiries@csiro.au Web:

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