Comments, Meta-Analyses, Studies and other Review articles
Swedish: Här följer en lista på studier som berör ämnet lågkolhydratkost, har du ändringar du anser borde göras eller förslag på studier som borde tas bort eller läggas till så maila mig på: email@example.com
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"Många tror att små studier kan negligeras, men faktum är att för att bevisa små behandlingseffekter krävs det stora studier, men stora behandlingseffekter kan bevisas i relativt små experiment". //Docent Ralf Sundberg.
English: Here is a list of studies concerning the subject of low-carbohydrate diets, do you have some changes you think should be done or suggestions for studies that should be removed or added, do email me at: firstname.lastname@example.org
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"Many believe that small studies can be neglected, but in fact, to prove small treatment effects you need major studies, but large treatment effects can be demonstrated in relatively small experiment". / / Associate Professor Ralf Sundberg.
Victor W. Ho et al. A Low Carbohydrate, High Protein Diet Slows Tumor Growth and Prevents Cancer Initiation. Cancer Res, 2011.
Since cancer cells depend on glucose more than normal cells, we compared the effects of low carbohydrate(CHO) diets to a Western diet on the growth rate of tumors in mice. To avoid caloric restriction–induced effects,we designed the low CHO diets isocaloric with the Western diet by increasing protein rather than fat levelsbecause of the reported tumor-promoting effects of high fat and the immune-stimulating effects of high protein.We found that both murine and human carcinomas grew slower in mice on diets containing low amylose CHOand high protein compared with a Western diet characterized by relatively high CHO and low protein. There wasno weight difference between the tumor-bearing mice on the low CHO or Western diets.Additionally, the low CHO-fed mice exhibited lower blood glucose, insulin, and lactate levels. Additiveantitumor effects with the low CHO diets were observed with the mTOR inhibitor CCI-779 and especially withthe COX-2 inhibitor Celebrex, a potent anti-inflammatory drug. Strikingly, in a genetically engineered mousemodel of HER-2/neu–induced mammary cancer, tumor penetrance in mice on a Western diet was nearly 50% bythe age of 1 year whereas no tumors were detected in mice on the low CHO diet. This difference was associatedwith weight gains in mice on the Western diet not observed in mice on the low CHO diet. Moreover, whereas only1 mouse on the Western diet achieved a normal life span, due to cancer-associated deaths, more than 50% of themice on the low CHO diet reached or exceeded the normal life span. Taken together, our findings offer acompelling preclinical illustration of the ability of a low CHO diet in not only restricting weight gain but alsocancer development and progression.
Thomas N. Seyfrieda et sl. Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res. (2011).
Malignant brain cancer persists as a major disease of morbidity and mortality. The failure to recognize brain cancer as a disease of energy metabolism has contributed in large part to the failure in management. As long as brain tumor cells have access to glucose and glutamine, the disease will progress. The current standard of care provides brain tumors with access to glucose and glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose availability and possibly that of glutamine when administered in carefully restricted amounts to reduce total caloric intake and circulating levels of glucose. The restricted KD (RKD) targets major signaling pathways associated with glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when evaluated in mice with malignant brain cancer. The therapeutic efficacy of the restricted KD can be enhanced when combined with drugs that also target glucose and glutamine. Therapeutic efficacy of the RKD was also seen against malignant gliomas in human case reports. Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer.
JOHN C. MAVROPOULOS et al. IS THERE A ROLE FOR A LOW-CARBOHYDRATE KETOGENIC DIET IN THE MANAGEMENT OF PROSTATE CANCER? UROLOGY 68: 15–18, 2006.
The relationship between diet and cancer developmentand/or growth remains very complex,because it involves consideration of numerousfactors. However, given the direct association betweenadoption of aWestern diet and prostate cancerincidence and mortality, it is difficult to imaginethat diet does not play some role in prostatecancer development and/or growth. The absence ofeffective therapy for men with advanced diseasesuggests that treatments are desperately needed.Novel dietary approaches are particularly appealingin this regard because of their low toxicity andpotential ease of application. In particular, a LCKDmay help to delay prostate cancer growth, becauseit can lower serum insulin and IGF-1 levels anddecrease caloric intake. Furthermore, as a LCKDresults in both greater weight loss and reductionsin serum insulin levels and total caloric intake relativeto low-fat diet, at least at 6 months whencompliance is still high, a LCKD may be a moreeffective dietary approach for prostate cancer management.However, enthusiasm must be tempered,given the concern for potential negative effectsrelated to the high-fat intake associated with aLCKD. It is hoped that preclinical studies, currentlyunder way in our laboratory, will provide acritical first step to reveal the possible benefitsand/or risks of a LCKD for prostate cancer management.
Rainer J Klement et al. Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutrition & Metabolism 2011.
Over the last years, evidence has accumulated suggesting that by systematically reducing theamount of dietary carbohydrates (CHO) one could suppress, or at least delay, the emergenceof cancer, and that proliferation of already existing tumor cells could be slowed down. Thishypothesis is supported by the association between modern chronic diseases like themetabolic syndrome and the risk of developing or dying from cancer. CHOs or glucose, towhich more complex carbohydrates are ultimately digested, can have direct and indirecteffects on tumor cell proliferation: first, contrary to normal cells, most malignant cells dependon steady glucose availability in the blood for their energy and biomass generating demandsand are not able to metabolize significant amounts of fatty acids or ketone bodies due tomitochondrial dysfunction. Second, high insulin and insulin-like growth factor (IGF)-1 levelsresulting from chronic ingestion of CHO-rich Western diet meals, can directly promote tumorcell proliferation via the insulin/IGF-1 signaling pathway. Third, ketone bodies that areelevated when insulin and blood glucose levels are low, have been found to negatively affectproliferation of different malignant cells in vitro or not to be usable by tumor cells formetabolic demands, and a multitude of mouse models have shown anti-tumorigenic propertiesof very low-CHO ketogenic diets. In addition, many cancer patients exhibit an altered glucosemetabolism characterized by insulin resistance and may profit from an increased protein andfat intake.In this review, we address the possible beneficial effects of low CHO diets on cancerprevention and treatment. Emphasis will be placed on the role of insulin and IGF-1 signalingin tumorigenesis as well as altered dietary needs of cancer patients.
Thomas N. Seyfried et al. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. British Journal of Cancer, 2003.
Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue thatcan derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapiesthat reduce plasma glucose and elevate ketone bodies in the CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice werefed either a standard diet unrestricted (SD-UR), a ketogenic diet unrestricted (KD-UR), the SD restricted to 40% (SD-R), or the KDrestricted to 40% of the control standard diet (KD-R). Body weights, tumour weights, plasma glucose, b-hydroxybutyrate (b-OHB),and insulin-like growth factor 1 (IGF-1) were measured 13 days after tumour implantation. CT-2A growth was rapid in both the SDURand KD-UR groups, but was significantly reduced in both the SD-R and KD-R groups by about 80%. The results indicate thatplasma glucose predicts CT-2A growth and that growth is dependent more on the amount than on the origin of dietary calories.Also, restriction of either diet significantly reduced the plasma levels of IGF-1, a biomarker for angiogenesis and tumour progression.Owing to a dependence on plasma glucose, IGF-1 was also predictive of CT-2A growth. Ketone bodies are proposed to reducestromal inflammatory activities, while providing normal brain cells with a nonglycolytic high-energy substrate. Our results in a mouseastrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevateketone bodies.
Thomas N. Seyfried et al. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets. Epilepsia, 2008.
Information is presented on the calorically restrictedketogenic diet (CRKD) as an alternativetherapy for brain cancer. In contrast to normalneurons and glia, which evolved to metabolize ketonebodies as an alternative fuel to glucose underenergy-restricted conditions, brain tumor cellsare largely glycolytic due to mitochondrial defectsand have a reduced ability to metabolize ketonebodies. The CRKD is effective in managing braintumor growth in animal models and in patients,and appears to act through antiangiogenic, antiinflammatory,and proapoptotic mechanisms.
Weihua Zhou et al. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutrition & Metabolism 2007, 4:5.
Background: Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the secondleading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-termmanagement because they ineffectively target tumor cells while negatively impacting the health and vitality of normal braincells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growthand survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated theefficacy of KetoCal®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, onthe growth and vascularity of a malignant mouse astrocytoma (CT-2A) and a human malignant glioma (U87-MG).
Methods: Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal® was administeredto the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to themanufacturers recommendation for children with refractory epilepsy. The effects KetoCal® on tumor growth,vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet.
Results: KetoCal® administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A andU87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of thecontrol groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal® diet reduced plasmaglucose levels while elevating plasma ketone body (â-hydroxybutyrate) levels. Tumor microvessel density was less in thecalorically restricted KetoCal® groups than in the calorically unrestricted control groups. Moreover, gene expression forthe mitochondrial enzymes, â-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, waslower in the tumors than in the contralateral normal brain suggesting that these brain tumors have reduced ability tometabolize ketone bodies for energy.
Conclusion: The results indicate that KetoCal® has anti-tumor and anti-angiogenic effects in experimental mouse andhuman brain tumors when administered in restricted amounts. The therapeutic effect of KetoCal® for brain cancermanagement was due largely to the reduction of total caloric content, which reduces circulating glucose required forrapid tumor growth. A dependency on glucose for energy together with defects in ketone body metabolism largelyaccount for why the brain tumors grow minimally on either a ketogenic-restricted diet or on a standard-restricted diet.Genes for ketone body metabolism should be useful for screening brain tumors that could be targeted with caloricallyrestricted high fat/low carbohydrate ketogenic diets. This preclinical study indicates that restricted KetoCal® is a safe andeffective diet therapy and should be considered as an alternative therapeutic option for malignant brain cancer.
Jeff S. Volek et al. An Isoenergetic Very Low Carbohydrate Diet Improves Serum HDL Cholesterol and Triacylglycerol Concentrations, the Total Cholesterol to HDL Cholesterol Ratio and Postprandial Lipemic Responses Compared with a Low Fat Diet in Normal Weight, Normolipidemic Women. J. Nutr. 2003. 133:2756–2761.
Very low carbohydrate diets are popular, yet little is known about their effects on blood lipids andother cardiovascular disease risk factors. We reported previously that a very low carbohydrate diet favorablyaffected fasting and postprandial triacylglycerols, LDL subclasses and HDL cholesterol (HDL-C) in men but theeffects in women are unclear. We compared the effects of a very low carbohydrate and a low fat diet on fastinglipids, postprandial lipemia and markers of inflammation in women. We conducted a balanced, randomized,two-period, crossover study in 10 healthy normolipidemic women who consumed both a low fat (30% fat) anda very low carbohydrate (10% carbohydrate) diet for 4 wk each. Two blood draws were performed on separatedays at 0, 2 and 4 wk and an oral fat tolerance test was performed at baseline and after each diet period. Comparedwith the low fat diet, the very low carbohydrate diet increased (P 0.05) fasting serum total cholesterol (16%), LDLcholesterol (LDL-C) (15%) and HDL-C (33%) and decreased serum triacylglycerols (30%), the total cholesterol toHDL ratio (13%) and the area under the 8-h postprandial triacylglycerol curve (31%). There were no significantchanges in LDL size or markers of inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-) after thevery low carbohydrate diet. In normal weight, normolipidemic women, a short-term very low carbohydrate dietmodestly increased LDL-C, yet there were favorable effects on cardiovascular disease risk status by virtue of arelatively larger increase in HDL-C and a decrease in fasting and postprandial triaclyglycerols.
Richard J. Wood et al. Carbohydrate Restriction Alters Lipoprotein Metabolism by Modifying VLDL, LDL, and HDL Subfraction Distribution and Size in Overweight Men. J. Nutr. 136: 384–389, 2006.
To determine the effects of carbohydrate restriction (CR) with and without soluble fiber on lipoproteinmetabolism, 29 men participated in a 12-wk weight loss intervention. Subjects were matched by age and BMI andrandomly assigned to consume 3 g/d of either a soluble fiber supplement (n ¼ 14) or placebo (n ¼ 15) witha macronutrient energy distribution of ;10% carbohydrate, ;65% fat, and ;25% protein. Because the groups did notdiffer in any of the variables measured, all data were pooled and comparisons were made between baseline and 12wk. After 12 wk, subjects had a mean weight loss of 7.5 kg (P , 0.001), and abdominal fat was reduced by 20% (P ,0.001). Plasma LDL cholesterol and triglycerides (TG) were significantly reduced by 8.9 and 38.6%, respectively.Similarly, apolipoproteins C-I (13.8%), C-III (21.2%) and E (12.5%) were significantly lower after theintervention. In contrast plasma HDL-cholesterol concentrations were increased by 12% (P , 0.05). Changes inplasma TG were positively correlated with reductions in large (r ¼ 0.615, P , 0.01) and medium VLDL particles (r ¼0.432, P , 0.05) and negatively correlated with LDL diameter (r ¼ 0.489, P , 0.01). Changes in trunk fat werepositively correlated with medium VLDL (r ¼ 0.474, P , 0.0) and small LDL (r ¼ 0.405, P , 0.05) and negativelycorrelated with large HDL (r ¼ 0.556, P , 0.01). We conclude that weight loss induced by CR favorably alters thesecretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreasedrisk for atherosclerosis and coronary heart disease.
Eric C Westman et al. Comparison of a reduced carbohydrate and reduced fat diet for LDL, HDL, and VLDL subclasses during 9-months of weight maintenance subsequent to weight loss. Lipids in Health and Disease 2010, 9:54.
Objectives: This study compared LDL, HDL, and VLDL subclasses in overweight or obese adults consuming either areduced carbohydrate (RC) or reduced fat (RF) weight maintenance diet for 9 months following significant weight loss.
Methods: Thirty-five (21 RC; 14 RF) overweight or obese middle-aged adults completed a 1-year weight managementclinic. Participants met weekly for the first six months and bi-weekly thereafter. Meetings included instruction for diet,physical activity, and behavior change related to weight management. Additionally, participants followed a liquid verylow-energy diet of ~2092 kJ per day for the first three months of the study. Subsequently, participants followed adietary plan for nine months that targeted a reduced percentage of carbohydrate (~20%) or fat (~30%) intake and anenergy intake level calculated to maintain weight loss. Lipid subclasses using NMR spectroscopy were analyzed prior toweight loss and at multiple intervals during weight maintenance.
Results: Body weight change was not significantly different within or between groups during weight maintenance (p> 0.05). The RC group showed significant increases in mean LDL size, large LDL, total HDL, large and small HDL, meanVLDL size, and large VLDL during weight maintenance while the RF group showed increases in total HDL, large andsmall HDL, total VLDL, and large, medium, and small VLDL (p < 0.05). Group*time interactions were significant for largeand medium VLDL (p > 0.05).
Conclusion: Some individual lipid subclasses improved in both dietary groups. Large and medium VLDL subclassesincreased to a greater extent across weight maintenance in the RF group.
Jeff S. Volek et al. Comparison of a Very Low-Carbohydrate and Low-Fat Diet on Fasting Lipids, LDL Subclasses, Insulin Resistance, and Postprandial Lipemic Responses in Overweight Women. ACN, Vol. 23, No. 2, 177–184 (2004).
Objective: Very low-carbohydrate diets are widely used for weight loss yet few controlled studies havedetermined how these diets impact cardiovascular risk factors compared to more traditional low-fat weight lossdiets. The primary purpose of this study was to compare a very low-carbohydrate and a low-fat diet on fastingblood lipids, LDL subclasses, postprandial lipemia, and insulin resistance in overweight and obese women.
Methods: Thirteen normolipidemic, moderately overweight (body fat 30%) women were prescribed twohypocaloric (500 kcal/day) diets for 4 week periods, a very low-carbohydrate (10% carbohydrate) and alow-fat (30% fat) diet. The diets were consumed in a balanced and randomized fashion. Two fasting blooddraws were performed on separate days and an oral fat tolerance test was performed at baseline, after the verylow-carbohydrate diet, and after the low-fat diet.
Results: Compared to corresponding values after the very low-carbohydrate diet, fasting total cholesterol,LDL-C, and HDL-C were significantly (p 0.05) lower, whereas fasting glucose, insulin, and insulin resistance(calculated using the homeostatic model assessment) were significantly higher after the low-fat diet. Both dietssignificantly decreased postprandial lipemia and resulted in similar nonsignificant changes in the total cholesterol/HDL-C ratio, fasting triacylglycerols, oxidized LDL, and LDL subclass distribution.
Conclusions: Compared to a low-fat weight loss diet, a short-term very low-carbohydrate diet did not lowerLDL-C but did prevent the decline in HDL-C and resulted in improved insulin sensitivity in overweight andobese, but otherwise healthy women. Small decreases in body mass improved postprandial lipemia, and thereforecardiovascular risk, independent of diet composition.
JAMES H. HAYS et al. Effect of a High Saturated Fat and No-Starch Diet on Serum Lipid Subfractions in Patients With Documented Atherosclerotic Cardiovascular Disease. Mayo Clin Proc. 2003;78:1331-1336.
Objective: To determine whether a diet of high saturatedfat and avoidance of starch (HSF-SA) results inweight loss without adverse effects on serum lipids in obesenondiabetic patients.
Patients and Methods: Twenty-three patients withatherosclerotic cardiovascular disease participated in aprospective 6-week trial at the Christiana Care MedicalCenter in Newark, Del, between August 2000 and September2001. All patients were obese (mean ± SD body massindex [BMI], 39.0±7.3 kg/m2) and had been treated withstatins before entry in the trial. Fifteen obese patients withpolycystic ovary syndrome (BMI, 36.1±9.7 kg/m2) and 8obese patients with reactive hypoglycemia (BMI, 46.8±10kg/m2) were monitored during an HSF-SA diet for 24 and52 weeks, respectively, between 1997 and 2000.
Results: In patients with atherosclerotic cardiovasculardisease, mean ± SD total body weight (TBW) decreased5.2%±2.5% (P<.001) as did body fat percentage (P=.02).Nuclear magnetic resonance spectroscopic analysis of lipidsshowed decreases in total triglycerides (P<.001), verylow-density lipoprotein (VLDL) triglycerides (P<.001),VLDL size (P<.001), large VLDL concentration (P<.001),and medium VLDL concentration (P<.001). High-densitylipoprotein (HDL) and LDL concentrations were unchanged,but HDL size (P=.01) and LDL size (P=.02) increased.Patients with polycystic ovary syndrome lost14.3%±20.3% of TBW (P=.008) and patients with reactivehypoglycemia lost 19.9%±8.7% of TBW (P<.001) at 24 and52 weeks, respectively, without adverse effects on serumlipids.
Conclusion: An HSF-SA diet results in weight loss after6 weeks without adverse effects on serum lipid levels verifiedby nuclear magnetic resonance, and further weight losswith a lipid-neutral effect may persist for up to 52 weeks.
Jeff S. Volek et al. Fasting Lipoprotein and Postprandial Triacylglycerol Responses to a Low-Carbohydrate Diet Supplemented with n-3 Fatty Acids. ACN, Vol. 19, No. 3, 383–391 (2000).
Background: The effects of a prolonged low-carbohydrate diet rich in n-3 fatty acids on blood lipid profileshave not been addressed in the scientific literature.
Objective: This study examined the effects of an eight-week ketogenic diet rich in n-3 fatty acids on fastingserum lipoproteins and postprandial triacylglycerol (TG) responses.
Design: Ten men consumed a low-carbohydrate diet rich in monounsaturated fat (MUFA) and supplementedwith n-3 fatty acids for eight weeks. Fasting blood samples were collected before and after one week of habitualdiet and on two consecutive days after 2, 4, 6 and 8 weeks of the intervention diet. Postprandial TG responsesto a fat-rich test meal were measured prior to and after the intervention diet.
Results: Compared to the habitual diet, subjects consumed significantly (p # 0.05) greater quantities ofprotein, fat, MUFA and n-3 fatty acids and significantly less total energy, carbohydrate and dietary fiber. Bodyweight significantly declined over the experimental period (24.2 6 2.7 kg). Compared to baseline, fasting totalcholesterol, LDL cholesterol and HDL cholesterol were not significantly different after the intervention diet(11.5%, 19.7% and 110.0%, respectively). Fasting TG were significantly reduced after the intervention diet(255%). There was a significant reduction in peak postprandial TG (242%) and TG area under the curve(248%) after the intervention diet.
Conclusions: A hypocaloric low-carbohydrate diet rich in MUFA and supplemented with n-3 fatty acidssignificantly reduced postabsorptive and postprandial TG in men that were not hypertriglyceridemic as a groupbefore the diet. This may be viewed as a clinically significant positive adaptation in terms of cardiovascular riskstatus. However, transient increases in total cholesterol and LDL cholesterol were also evident and should beexamined further in regard to which particular subfractions are elevated.
Lars Berglund et al. HDL-subpopulation patterns in response to reductions in dietary total and saturated fat intakes in healthy subjects. Am J Clin Nutr 1999;70:992–1000.
Background: Little information is available about HDL subpopulations during dietary changes.
Objective: The objective was to investigate the effect of reductions in total and saturated fat intakes on HDL subpopulations.
Design: Multiracial, young and elderly men and women (n = 103) participating in the double-blind, randomized DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activities) Study consumed 3 different diets, each for 8 wk: an average American diet (AAD: 34.3% total fat,15.0% saturated fat), the American Heart Association Step I diet (28.6% total fat, 9.0% saturated fat), and a diet low in saturated fat (25.3% total fat, 6.1% saturated fat).
Results: HDL2-cholesterol concentrations, by differential precipitation, decreased (P < 0.001) in a stepwise fashion after the reduction of total and saturated fat: 0.58 ± 0.21, 0.53 ± 0.19, and 0.48 ± 0.18 mmol/L with the AAD, Step I, and low-fat diets, respectively. HDL3 cholesterol decreased (P < 0.01) less: 0.76 ± 0.13, 0.73 ± 0.12, and 0.72 ± 0.11 mmol/L with the AAD, Step I, and low-fat diets, respectively. As measured by nondenaturing gradient gel electrophoresis, the larger-size HDL2b subpopulation decreased with the reduction in dietary fat, and a corresponding relative increase was seen for the smaller-sized HDL3a, 3b, and 3c subpopulations (P < 0.01). HDL2-cholesterol concentrations correlated negatively with serum triacylglycerol concentrations on all 3 diets: r = 20.46, 20.37, and 20.45 with the AAD, Step I, and low-fat diets, respectively (P < 0.0001). A similar negative correlation was seen for HDL2b, whereas HDL3a, 3b, and 3c correlated positively with triacylglycerol concentrations. Diet-induced changes in serum triacylglycerol were negatively correlated with changes in HDL2 and HDL2b cholesterol.
Conclusions: A reduction in dietary total and saturated fat decreased both large (HDL2 and HDL2b) and small, dense HDL subpopulations, although decreases in HDL2 and HDL2b were most pronounced.
Ravnskov U. High cholesterol may protect against infections and atherosclerosis. QJM (2003) 96 (12): 927-934.
Many researchers have suggested that the blood lipids play a key role in the immune defence system. There is also a growing understanding that an inflammatory response of the arterial intima to injury is a crucial step in the genesis of atherosclerosis. and that infections may be one type of such injury.22 These two concepts are difficult to harmonize with the low-density-lipoprotein (LDL) receptor hypothesis, according to which high LDL cholesterol is the most important cause of atherosclerosis. However, the many observations that conflict with the LDL receptor hypothesis, may be explained by the idea that high serum cholesterol and/or high LDL is protective against infection and atherosclerosis.
Jeff S Volek et al. Low carbohydrate diets improve atherogenic dyslipidemia even in the absence of weight loss. Nutrition & Metabolism 2006, 3:24.
Because of its effect on insulin, carbohydrate restriction is one of the obvious dietary choices forweight reduction and diabetes. Such interventions generally lead to higher levels of dietary fat thanofficial recommendations and have long been criticized because of potential effects oncardiovascular risk although many literature reports have shown that they are actually protectiveeven in the absence of weight loss. A recent report of Krauss et al. (AJCN, 2006) separates theeffects of weight loss and carbohydrate restriction. They clearly confirm that carbohydraterestriction leads to an improvement in atherogenic lipid states in the absence of weight loss or inthe presence of higher saturated fat. In distinction, low fat diets seem to require weight loss foreffective improvement in atherogenic dyslipidemia.
Jeff S. Volek et al. Modification of Lipoproteins by Very Low-Carbohydrate Diets. J. Nutr. 2005. 135: 1339–1342.
Very low-carbohydrate diets (VLCDs) arepopular, but remain controversial. This review summarizesthe latest studies that have examined the effects of VLCDson lipoproteins and related risk factors for cardiovasculardisease. Prospective studies indicate that VLCDs improvethe lipoprotein profile independently of weight loss. Althoughnot as effective at lowering LDL cholesterol (LDLC),VLCDs consistently improve postabsorptive and postprandialtriacylglycerols (TAGs), HDL cholesterol (HDL-C),and the distribution of LDL-C subfractions to a greaterextent than low-fat diets. VLCDs also improve proinflammatorymarkers when associated with weight loss. Studiesusually report mean lipid responses, but individual dataindicate a large degree of variability in the magnitude and insome cases the direction (e.g., LDL-C) of lipoprotein responsesto both low-fat and VLCDs. Such variability makesit hard to defend a single diet recommendation, especiallyconsidering the potential for low-fat/high-carbohydrate dietsto exacerbate TAG, HDL-C, and other characteristics ofthe metabolic syndrome. Considering the effectiveness ofVLCDs in promoting fat loss and improving the metabolicsyndrome, discounting or condemning their use is unjustified.We encourage a more unbiased, balanced appraisal ofVLCDs.
Ronald M Krauss et al. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 2006;83:1025–31.
Background: Low-carbohydrate diets have been used to manageobesity and its metabolic consequences.
Objective: The objective was to study the effects of moderate carbohydraterestriction on atherogenic dyslipidemia before and afterweight loss and in conjunction with a low or high dietary saturatedfat intake.
Design: After 1 wk of consuming a basal diet, 178 men with a meanbody mass index (in kg/m2) of 29.2 2.0 were randomly assignedto consume diets with carbohydrate contents of 54% (basal diet),39%, or 26% of energy and with a low saturated fat content (7–9%of energy); a fourth group consumed a diet with 26% of energy ascarbohydrate and 15% as saturated fat. After 3 wk, the mean weightloss (5.12 1.83 kg) was induced in all diet groups by a reductionof 1000 kcal/d for 5 wk followed by 4 wk of weight stabilization.
Results: The 26%-carbohydrate, low-saturated-fat diet reduced triacylglycerol,apolipoprotein B, small LDL mass, and total:HDLcholesterol and increased LDL peak diameter. These changes weresignificantly different from those with the 54%-carbohydrate diet.After subsequent weight loss, the changes in all these variables weresignificantly greater and the reduction in LDL cholesterol was significantlygreater with the 54%-carbohydrate diet than with the 26%-carbohydrate diet. With the 26%-carbohydrate diet, lipoproteinchanges with the higher saturated fat intakes were not significantlydifferent from those with the lower saturated fat intakes, except forLDL cholesterol, which decreased less with the higher saturated fatintake because of an increase in mass of large LDL.
Conclusions: Moderate carbohydrate restriction and weight lossprovide equivalent but nonadditive approaches to improving atherogenicdyslipidemia. Moreover, beneficial lipid changes resultingfrom a reduced carbohydrate intake were not significant after weightloss.
Matthew J. Sharman et al. Very Low-Carbohydrate and Low-Fat Diets Affect Fasting Lipids and Postprandial Lipemia Differently in Overweight Men. J. Nutr. 2004. 134: 880–885.
Hypoenergetic very low-carbohydrate and low-fat diets are both commonly used for short-termweight loss; however, few studies have directly compared their effect on blood lipids, with no studies to ourknowledge comparing postprandial lipemia, an important independently identified cardiovascular risk factor. Theprimary purpose of this study was to compare the effects of a very low-carbohydrate and a low-fat diet on fastingblood lipids and postprandial lipemia in overweight men. In a balanced, randomized, crossover design, overweightmen (n 15; body fat 25%; BMI, 34 kg/m2) consumed 2 experimental diets for 2 consecutive 6-wk periods. Onewas a very low-carbohydrate (10% energy as carbohydrate) diet and the other a low-fat (30% energy as fat)diet. Blood was drawn from fasting subjects on separate days and an oral fat tolerance test was performed atbaseline, after the very low-carbohydrate diet period, and after the low-fat diet period. Both diets had the sameeffect on serum total cholesterol, serum insulin, and homeostasis model analysis-insulin resistance (HOMA-IR).Neither diet affected serum HDL cholesterol (HDL-C) or oxidized LDL (oxLDL) concentrations. Serum LDLcholesterol (LDL-C) was reduced (P 0.05) only by the low-fat diet (18%). Fasting serum triacylglycerol (TAG),the TAG/HDL-C ratio, and glucose were significantly reduced only by the very low-carbohydrate diet (44, –42,and –6%, respectively). Postprandial lipemia was significantly reduced when the men consumed both dietscompared with baseline, but the reduction was significantly greater after intake of the very low-carbohydrate diet.Mean and peak LDL particle size increased only after the very low-carbohydrate diet. The short-term hypoenergeticlow-fat diet was more effective at lowering serum LDL-C, but the very low-carbohydrate diet was more effectiveat improving characteristics of the metabolic syndrome as shown by a decrease in fasting serum TAG, theTAG/HDL-C ratio, postprandial lipemia, serum glucose, an increase in LDL particle size, and also greater weightloss (P 0.05).
Coronary heart disease and cardiovascular mortality
Sung-Hee Park et al. Dietary carbohydrate intake is associated with cardiovascular disease riskin Korean: Analysis of the third Korea National Health and Nutrition Examination Survey (KNHANES III). IJC 2010, 139, 234–240.
Background: It is widely recognized that dietary factors play important roles in the development of cardiovascular disease (CVD). We evaluated the association between carbohydrate intake and CVD risk factors, using data from the third Korea National Health and Nutrition Examination Survey (KNHANES III).
Methods: A nationally representative sample of Korean adults (1536 men, 2235 women), aged 20 to 69 years, was divided into three groups according to carbohydrate intake (% of energy), based on the Dietary Reference Intakes (DRI, 55–70% of energy) for Koreans. Then, we examined whether excessive carbohydrate intake was related to CVD risk factors.
Results: Mean carbohydrate intake (% of energy) was 72.8% (321 g/day), above the DRI for Korean adults (55–70%). A high carbohydrate intake (N70% of energy) was associated with higher BMI, blood pressure, fasting glucose, triglycerides, and LDL-cholesterol levels in women. After adjusting for covariates, such as age, energy intake, alcohol consumption, smoking status, and physical activity, high carbohydrate intakes (N70% of energy) were significantly associated with diabetes mellitus and low HDL-cholesterol (HDL-C) in women. In men, however, only total cholesterol was inversely associated with high carbohydrate intake.
Conclusion: Higher carbohydrate intakes than the DRI for Koreans were significantly associated with diabetes mellitus and low HDL-C levels in women. These results suggest that improvement of dietary patterns may be an important approach to the prevention of CVD in Korean women.
Dariush Mozaffarian et al. Dietary fats, carbohydrate, and progression of coronaryatherosclerosis in postmenopausal women. Am J Clin Nutr 2004;80:1175–84.
Background: The influence of diet on atherosclerotic progression is not well established, particularly in postmenopausal women, in whom risk factors for progression may differ from those for men.
Objective: The objective was to investigate associations between dietary macronutrients and progression of coronary atherosclerosis among postmenopausal women.
Design: Quantitative coronary angiography was performed at baseline and after a mean follow-up of 3.1 y in 2243 coronary segments in 235 postmenopausal women with established coronary heart disease. Usual dietary intake was assessed at baseline.
Results: The mean (SD) total fat intake was 25 6% of energy. In multivariate analyses, a higher saturated fat intake was associated with a smaller decline in mean minimal coronary diameter (P 0.001) and less progression of coronary stenosis (P0.002) during follow-up. Compared with a 0.22-mm decline in the lowest quartile of intake, there was a 0.10-mm decline in the second quartile (P 0.002), a 0.07-mm decline in the third quartile (P 0.002), and no decline in the fourth quartile (P0.001); P for trend0.001. This inverse association was more pronounced among women with lower
monounsaturated fat (P for interaction0.04) and higher carbohydrate (P for interaction0.004) intakes and possibly lower total fat intake (Pfor interaction0.09). Carbohydrate intake was positively associated with atherosclerotic progression (P0.001), particularly when the glycemic index was high. Polyunsaturated fat intake was positively associated with progression when replacing other fats (P 0.04) but not when replacing carbohydrate or protein. Monounsaturated and total fat intakes were not associated with progression.
Conclusions: In postmenopausal women with relatively low total fat intake, a greater saturated fat intake is associated with less progression of coronary atherosclerosis, whereas carbohydrate intake is associated with a greater progression.
Göran Berglund et al. Fettintag och kardiovaskulärhälsa – är vi helt felinformerade. Läkartidningen nr 49–50 2007 volym 104.
Nya resultat från primärpreventiva interventionsstudier med långvarig sänkning av kostintag av såväl totalfett som mättat fett visar ingen signifikant effekt på risken att insjukna i cancer eller hjärt–kärlsjukdom. Fynden är i linje med en längre tids samlade observationsstudier.
Gällande kostrekommendationer för prevention och behandling av t ex hjärt–kärlsjukdom säger enhälligt att befolkningen kraftigt bör sänka sitt intag av fett, framför allt intaget av mättat fett och transfetter.
Vi behöver nu en ny vetenskaplig debatt och strukturerade systematiska analyser av hela det publicerade underlaget för sambandet mellan fettintag och allvarliga sjukdomar som cancer och hjärtkärlsjukdom. Först då kan nya, vetenskapligt grundade rekommendationer utarbetas.
Thomas L. Halton et al. Low-Carbohydrate-Diet Score and the Riskof Coronary Heart Disease in Women. N Engl J Med. 2006 Nov 9;355(19):1991-2002.
Background: Low-carbohydrate diets have been advocated for weight loss and to prevent obesity, but the long-term safety of these diets has not been determined.
Methods: We evaluated data on 82,802 women in the Nurses’ Health Study who had completed a validated food-frequency questionnaire. Data from the questionnaire were used to calculate a low-carbohydrate-diet score, which was based on the percentage of energy as carbohydrate, fat, and protein (a higher score reflects a higher intake of fat and protein and a lower intake of carbohydrate). The association between the low-carbohydrate-diet score and the risk of coronary heart disease was examined.
Results: During 20 years of follow-up, we documented 1994 new cases of coronary heart disease. After multivariate adjustment, the relative risk of coronary heart disease comparing highest and lowest deciles of the low-carbohydrate-diet score was 0.94 (95% confidence interval [CI], 0.76 to 1.18; P for trend = 0.19). The relative risk comparing highest and lowest deciles of a low-carbohydrate-diet score on the basis of the percentage of energy from carbohydrate, animal protein, and animal fat was 0.94 (95% CI, 0.74 to 1.19; P for trend = 0.52), whereas the relative risk on the basis of the percentage of energy from intake of carbohydrates, vegetable protein, and vegetable fat was 0.70 (95% CI, 0.56 to 0.88; P for trend = 0.002). A higher glycemic load was strongly associated with an increased risk of coronary heart disease (relative risk comparing highest and lowest deciles, 1.90; 95% CI, 1.15 to 3.15; P for trend = 0.003).
Conclusions: Our findings suggest that diets lower in carbohydrate and higher in protein and fat are not associated with increased risk of coronary heart disease in women. When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease.
Ronald M Krauss et al. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr 2010.
Background: A reduction in dietary saturated fat has generallybeen thought to improve cardiovascular health.
Objective: The objective of this meta-analysis was to summarizethe evidence related to the association of dietary saturated fat withrisk of coronary heart disease (CHD), stroke, and cardiovasculardisease (CVD; CHD inclusive of stroke) in prospective epidemiologicstudies.
Design: Twenty-one studies identified by searching MEDLINE andEMBASE databases and secondary referencing qualified for inclusionin this study. A random-effects model was used to derivecomposite relative risk estimates for CHD, stroke, and CVD.
Results: During 5–23 y of follow-up of 347,747 subjects, 11,006developed CHD or stroke. Intake of saturated fat was not associatedwith an increased risk of CHD, stroke, or CVD. The pooled relativerisk estimates that compared extreme quantiles of saturated fat intakewere 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95%CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11;P = 0.95) for CVD. Consideration of age, sex, and study quality didnot change the results.
Conclusions: A meta-analysis of prospective epidemiologic studiesshowed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHDor CVD. More data are needed to elucidate whether CVD risks arelikely to be influenced by the specific nutrients used to replacesaturated fat.
Hussein M. Dashti et al. Ketogenic Diet Modifies the Risk Factors of HeartDisease in Obese Patients. Nutrition 2003, 19:901–902.
Joaquín Pérez-Guisado et al. Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss. Nutrition Journal 2008, 7:30.
Background: Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine.
Methods: A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 ± 2.22 and 38.48 ± 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat (≥30 ml/day), moderate red wine intake (200–400 ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between
the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's t test.
Results: There was an extremely significant (p < 0.0001) reduction in body weight (108.62 kg→94.48 kg), body mass index (36.46 kg/m2→31.76 kg/m2), systolic blood pressure (125.71mmHg→109.05 mmHg), diastolic blood pressure (84.52 mmHg→ 75.24 mmHg), total cholesterol (208.24 mg/dl→186.62 mg/dl), triacylglicerols (218.67 mg/dl→113.90 mg/dl) and glucose (109.81mg/dl→ 93.33 mg/dl). There was a significant (p = 0.0167) reduction in LDLc (114.52 mg/
dl→105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl→54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction).
Conclusion: The SKMD is safe, an effective way of losing weight, promoting non-atherogenic lipid profiles, lowering blood pressure and improving fasting blood glucose levels. Future research should include a larger sample size, a longer term use and a comparison with other ketogenic diets.
Diabetes and Insulin Resistens
Jørgen Vesti Nielsen et al. A low-carbohydrate diet may prevent end-stage renal failure in type 2 diabetes. A case report. Nutrition & Metabolism 2006, 3:23.
An obese patient with type 2 diabetes whose diet was changed from the recommended highcarbohydrate, low-fat type to a low-carbohydrate diet showed a significant reduction in bodyweight, improved glycemic control and a reversal of a six year long decline of renal function. The reversal of the renal function was likely caused by both improved glycemic control and elimination of the patient's obesity. Insulin treatment in type 2 diabetes patients usually leads to weight increase which may cause further injury to the kidney. Although other unknown metabolic mechanisms cannot be excluded, it is likely that the obesity caused by the combination of high-carbohydrate diet and insulin in this case contributed to the patient's deteriorating kidney function. In such patients, where control of bodyweight and hyperglycemia is vital, a trial with a low-carbohydrate diet may be appropriate to avoid the risk of adding obesity-associated renal failure to already failing kidneys.
Jørgen Vesti Nielsen et al. A Low Carbohydrate Diet in Type 1 Diabetes: Clinical Experience – A Brief Report. Upsala J Med Sci 110 (3): 267–273, 2005.
Due to failure to achieve control twenty-two patients with type 1 diabetes with symptomatic
fluctuating blood glucose started on a diet limited to 70-90 g carbohydrates per day and were taught to match the insulin doses accordingly. The caloric requirements were covered by an increased intake of protein and fat. The purpose was to reduce the blood glucose fluctuations, the rate of hypoglycaemia and to improve HbA1c. After three and 12 months the rate of hypoglycaemia was significantly lowered from 2.9 + 2.0 to 0.2 + 0.3 and 0.5 + 0.5 episodes per week respectively. The HbA1c level was significantly lowered from 7.5 + 0.9 % to 6.4 + 0.7 % after three months and was
still after 12 months 6.4 + 0.8 %. The meal insulin requirements were reduced from 21.1 + 6.7 I.U./day to 12.7 + 3.5 I.U./day and 12.4 + 2.6 I.U./day after three and 12 months respectively. Furthermore the triglyceride level was significantly lowered whereas the levels for total cholesterol and HDL-cholesterol were unchanged.
Conclusion: the present report shows that a 70-90 g carbohydrate diet is a feasible long-term alternative in the treatment of type 1 diabetes and leads to improved glycaemic control.
William S Yancy Jr et al. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutrition & Metabolism 2005, 2:34.
Background: The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving glycemia and reducing medications in patients with type 2 diabetes.
Methods: From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation. Participants returned every other week for measurements, counseling, and further medication adjustment. The primary outcome was hemoglobin A1c.
Results: Twenty-one of the 28 participants who were enrolled completed the study. Twenty participants were men; 13 were White, 8 were African-American. The mean [± SD] age was 56.0 ± 7.9 years and BMI was 42.2 ± 5.8 kg/m2. Hemoglobin A1c decreased by 16% from 7.5 ± 1.4% to 6.3 ± 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7 participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight decreased by 6.6% from 131.4 ± 18.3 kg to 122.7 ± 18.9 kg (p < 0.001). In linear regression analyses, weight change at 16 weeks did not predict change in hemoglobin A1c. Fasting serum triglyceride decreased 42% from 2.69 ± 2.87 mmol/L to 1.57 ± 1.38 mmol/L (p = 0.001) while other serum lipid measurements did not change significantly.
Conclusion: The LCKD improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication.
Miyashita Y et al. Beneficial effect of low carbohydrate in low calorie diets on visceral fat reduction in type 2 diabetic patients with obesity. Diabetes Res Clin Pract. 2004 Sep;65(3):235-41.
The adequate composition of carbohydrate and fat in low calorie diets for type 2 diabetes mellitus patients with obesity is not fully established. The aim of this study was to investigate the effects of low carbohydrate diet on glucose and lipid metabolism, especially on visceral fat accumulation, and comparing that of a high carbohydrate diet. Obese subjects with type 2 diabetes mellitus were randomly assigned to take a low calorie and low carbohydrate diet (n = 11, 1000 kcal per day, protein:carbohydrate:fat = 25:40:35) or a low calorie and high carbohydrate diet (n = 11, 1000 kcal per day, protein:carbohydrate:fat = 25:65:10) for 4 weeks. Similar decreases in body weight and serum glucose levels were observed in both groups. Fasting serum insulin levels were reduced in the low carbohydrate diet group compared to the high carbohydrate diet group (-30% versus -10%, P < 0.05). Total serum cholesterol and triglyceride levels decreased in both groups, but were not significantly different from each other. High-density lipoprotein-cholesterol (HDL-C) increased in the low carbohydrate diet group but not in the high carbohydrate diet group (+15% versus 0%, P < 0.01). There was a larger decrease in visceral fat area measured by computed tomography in the low carbohydrate diet group compared to the high carbohydrate diet group (-40 cm(2) versus -10 cm(2), P < 0.05). The ratio of visceral fat area to subcutaneous fat area did not change in the high carbohydrate diet group (from 0.70 to 0.68), but it decreased significantly in the low carbohydrate diet group (from 0.69 to 0.47, P < 0.005). These results suggest that, when restrict diet was made isocaloric, a low calorie/low carbohydrate diet might be more effective treatment for a reduction of visceral fat, improved insulin sensitivity and increased in HDL-C levels than low calorie/high carbohydrate diet in obese subjects with type 2 diabetes mellitus.
Vernon MC et al. Clinical experience of a carbohydrate-restricted diet: effect on diabetes mellitus. Metab Syndr Relat Disord. 2003 Sep;1(3):233-7.
Davis NJ et al. Comparative study of the effects of a 1-year dietary intervention of a low-carbohydrate diet versus a low-fat diet on weight and glycemic control in type 2 diabetes. Diabetes Care. 2009 Jul;32(7):1147-52. Epub 2009 Apr 14.
OBJECTIVE: To compare the effects of a 1-year intervention with a low-carbohydrate and a low-fat diet on weight loss and glycemic control in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS: This study is a randomized clinical trial of 105 overweight adults with type 2 diabetes. Primary outcomes were weight and A1C. Secondary outcomes included blood pressure and lipids. Outcome measures were obtained at 3, 6, and 12 months.
RESULTS: The greatest reduction in weight and A1C occurred within the first 3 months. Weight loss occurred faster in the low-carbohydrate group than in the low-fat group (P = 0.005), but at 1 year a similar 3.4% weight reduction was seen in both dietary groups. There was no significant change in A1C in either group at 1 year. There was no change in blood pressure, but a greater increase in HDL was observed in the low-carbohydrate group (P = 0.002).
CONCLUSIONS: Among patients with type 2 diabetes, after 1 year a low-carbohydrate diet had effects on weight and A1C similar to those seen with a low-fat diet. There was no significant effect on blood pressure, but the low-carbohydrate diet produced a greater increase in HDL cholesterol.
Ralf Sundberg. Dagens kostråd vid diabetes mellitus saknar vetenskaplig evidens. Pressrelease Symposium 57.
Nuvarande kostråd har aldrig testats i kontrollerade studier
Min kritik mot Manns et al. guidelineartikel är dessutom relevant eftersom råden att öka intaget av kolhydrater för diabetiker grundar sig endast på spekulationer. Dessa råd har aldrig genomgått kontrollerade kliniska studier, vilket artikelförfattarna också medger.
Jan Östman. Diabetesbehandlingen i ett 100-årigt perspektiv. Läkartidningen ❙ Nr 51–52 ❙ 2004 ❙ Volym 101.
I och med upptäckten av bukspottkörtelns roll för matsmältningen, i slutet av 1800-talet, startade sökandet efter den faktor i pankreas som reglerar glukosomsättningen. Ett sökande som under 1900-talets första decennier resulterade i upptäckten av insulinet, vilket möjliggjorde en väsentligt sänkt dödlighet i diabeteskoma. I slutet av 1960- talet introducerades pankreastransplantationer, och senare transplantation av endast endokrin vävnad, som behandlingsmetod. Diabetesbehandlingen och dess förgrundsgestalter har skildrats i över 500 artiklar i Läkartidningen.
Eric C. Westman et al. Dietary Treatment of Diabetes Mellitus in the Pre-Insulin Era (1914–1922). Perspectives in Biology and Medicine, volume 49, number 1 (winter 2006):77–83.
Before the discovery of insulin, one of the most common dietary treatments of diabetes mellitus was a high-fat, low-carbohydrate diet.A review of Frederick M. Allen’s case histories shows that a 70% fat, 8% carbohydrate diet could eliminate glycosuria among hospitalized patients. A reconsideration of the role of the highfat, low-carbohydrate diet for the treatment of diabetes mellitus is in order.
Gannon MC et al. Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes. 2004 Sep;53(9):2375-82.
There has been interest in the effect of various types and amounts of dietary carbohydrates and proteins on blood glucose. On the basis of our previous data, we designed a high-protein/low-carbohydrate, weight-maintaining, nonketogenic diet. Its effect on glucose control in people with untreated type 2 diabetes was determined. We refer to this as a low-biologically-available-glucose (LoBAG) diet. Eight men were studied using a randomized 5-week crossover design with a 5-week washout period. The carbohydrate:protein:fat ratio of the control diet was 55:15:30. The test diet ratio was 20:30:50. Plasma and urinary beta-hydroxybutyrate were similar on both diets. The mean 24-h integrated serum glucose at the end of the control and LoBAG diets was 198 and 126 mg/dl, respectively. The percentage of glycohemoglobin was 9.8 +/- 0.5 and 7.6 +/- 0.3, respectively. It was still decreasing at the end of the LoBAG diet. Thus, the final calculated glycohemoglobin was estimated to be approximately 6.3-5.4%. Serum insulin was decreased, and plasma glucagon was increased. Serum cholesterol was unchanged. Thus, a LoBAG diet ingested for 5 weeks dramatically reduced the circulating glucose concentration in people with untreated type 2 diabetes. Potentially, this could be a patient-empowering way to ameliorate hyperglycemia without pharmacological intervention. The long-term effects of such a diet remain to be determined.
Boden G et al. Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med. 2005 Mar 15;142(6):403-11.
BACKGROUND: It is not known how a low-carbohydrate, high-protein, high-fat diet causes weight loss or how it affects blood glucose levels in patients with type 2 diabetes.
OBJECTIVE: To determine effects of a strict low-carbohydrate diet on body weight, body water, energy intake and expenditure, glycemic control, insulin sensitivity, and lipid levels in obese patients with type 2 diabetes.
DESIGN: Inpatient comparison of 2 diets.
SETTING: General clinical research center of a university hospital.
PATIENTS: 10 obese patients with type 2 diabetes.
INTERVENTION: Usual diets for 7 days followed by a low-carbohydrate diet for 14 days.
MEASUREMENTS: Body weight, water, and composition; energy intake and expenditure; diet satisfaction; hemoglobin A1c; insulin sensitivity; 24-hour urinary ketone excretion; and plasma profiles of glucose, insulin, leptin, and ghrelin.
RESULTS: On the low-carbohydrate diet, mean energy intake decreased from 3111 kcal/d to 2164 kcal/d. The mean energy deficit of 1027 kcal/d (median, 737 kcal/d) completely accounted for the weight loss of 1.65 kg in 14 days (median, 1.34 kg in 14 days). Mean 24-hour plasma profiles of glucose levels normalized, mean hemoglobin A1c decreased from 7.3% to 6.8%, and insulin sensitivity improved by approximately 75%. Mean plasma triglyceride and cholesterol levels decreased (change, -35% and -10%, respectively).
LIMITATIONS: The study was limited by the short duration, small number of participants, and lack of a strict control group.
CONCLUSION: In a small group of obese patients with type 2 diabetes, a low-carbohydrate diet followed for 2 weeks resulted in spontaneous reduction in energy intake to a level appropriate to their height; weight loss that was completely accounted for by reduced caloric intake; much improved 24-hour blood glucose profiles, insulin sensitivity, and hemoglobin A1c; and decreased plasma triglyceride and cholesterol levels. The long-term effects of this diet, however, remain uncertain.
Hajime Haimoto et al. Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes. Nutrition & Metabolism 2009, 6:21.
We previously demonstrated that a loosely restricted 45%-carbohydrate diet led to greater reduction in hemoglobin A1c (HbA1c) compared to high-carbohydrate diets in outpatients with mild type 2 diabetes (mean HbA1c level: 7.4%) over 2 years. To determine whether good glycemic control can be achieved with a 30%-carbohydrate diet in severe type 2 diabetes, 33 outpatients (15 males, 18 females, mean age: 59 yrs) with HbA1c levels of 9.0% or above were instructed to follow a low-carbohydrate diet (1852 kcal; %CHO:fat:protein = 30:44:20) for 6 months in an outpatient
clinic and were followed to assess their HbA1c levels, body mass index and doses of antidiabetic drugs. HbA1c levels decreased sharply from a baseline of 10.9 ± 1.6% to 7.8 ± 1.5% at 3 months and to 7.4 ± 1.4% at 6 months. Body mass index decreased slightly from baseline (23.8 ± 3.3) to 6 months (23.5 ± 3.4). Only two patients dropped out. No adverse effects were observed except for mild constipation. The number of patients on sulfonylureas decreased from 7 at baseline to 2 at 6 months. No patient required inpatient care or insulin therapy. In summary, the 30% carbohydrate diet over 6 months led to a remarkable reduction in HbA1c levels, even among outpatients with severe type 2 diabetes, without any insulin therapy, hospital care or increase in sulfonylureas. The effectiveness of the diet may be comparable to that of insulin therapy.
Richard D. Feinman. Fad Diets in the Treatment of Diabetes. Curr Diab Rep 2011.
Use of the term “fad diet” reflects the contentious nature of the debate in the treatment of diabetes and generally targets diets based on carbohydrate restriction, the major challenge to traditional dietary therapy. Although standard low-fat diets more accurately conform to the idea of a practice supported by social pressure rather than scientific data, it is suggested that we might want to give up altogether unscientific terms like “fad” and “healthy.” Far from faddish, diets based on carbohydrate restriction have been the historical treatment for diabetes and are still supported by basic biochemistry, and it is argued that they should be considered the “default” diet, the one to try first, in diseases of carbohydrate intolerance or insulin resistance. The barrier to acceptance of low-carbohydrate diets in the past has been concern about saturated fat, which might be substituted for the carbohydrate that is removed. However, recent re-analysis of much old data shows that replacing carbohydrate with saturated fat is, if anything, beneficial. The dialectic of impact of continued hemoglobin A1c versus effect of dietary saturated fat in the risk of cardiovascular disease is resolved in direction of glycemic control. Putting biased language behind us and facing the impact of recent results that point to the value of low-carbohydrate diets would offer patients the maximum number of options.
Eric C Westman et al. Has carbohydrate-restriction been forgotten as a treatment for diabetes mellitus? A perspective on the ACCORD study design. Nutrition & Metabolism 2008, 5:10.
Prior to the discovery of medical treatment for diabetes, carbohydrate-restriction was the predominant treatment recommendation to treat diabetes mellitus. In this commentary we argue that carbohydrate-restriction should be reincorporated into contemporary treatment studies for diabetes mellitus.
Eric C Westman et al. Insulin Resistance from a Low Carbohydrate, High Fat Diet Perspective. Metab Syndr Relat Disord. 2005;3(1):14-8.
INSULIN RESISTANCE IS A major factor in the developmentof diabetes, hypertension, obesity andcardiovascular disease. The prevailing paradigmfor the understanding of insulin resistanceis based upon the concept of fatty-acid mediatedinhibition of glucose oxidation. Arecent reviewmore generally states that there is a “generalizeddefect in the insulin-signaling pathway.” Basedon this model, much of the research investigatingtreatment of insulin resistance has focusedon the facilitation of glucose entry into the cell. Perhaps insulin resistance has proved difficultto treat because we are thinking about the problemone-dimensionally. What if insulin resistanceis an adaptation to reduce the energy influxbecause the cell already has sufficient energysubstrate? The implications of this basic teleologicalexplanation are profound: to reduce insulinresistance, instead of trying only to increase glucoseuptake or disposal, we could accomplishthe same end by reducing glucose appearance. Several lines of evidence, including recent clinicalresearch regarding low carbohydrate ketogenicdiets support this redirection of thinking.
Jørgen Vesti Nielsen et al. Lasting Improvement of Hyperglycaemia and Bodyweight: Low-carbohydrate Diet in Type 2 Diabetes. A Brief Report. Upsala J Med Sci 109: 179–184, 2005.
In two groups of obese patients with type 2 diabetes the effects of 2 different diet compositions were tested with regard to glycaemic control and bodyweight. A group of 16 obese patients with type 2 diabetes was advised on a low-carbohydrate diet, 1800 kcal for men and 1600 kcal for women, distributed as 20 % carbohydrates, 30 % protein and 50 % fat. Fifteen obese diabetes patients on a high-carbohydrate diet were control group. Their diet, 1600–1800 kcal for men and 1400–1600 kcal for women, consisted of approximately 60 % carbohydrates, 15 % protein and 25 % fat. Positive effects on the glucose levels were seen very soon. After 6 months a marked reduction in bodyweight of patients in the low-carbohydrate diet group was observed, and this remained one year later. After 6 months the mean changes in the low-carbohydrate group and the control group respectively were (±SD): fasting blood glucose (f-BG): –3.4 ± 2.9 and –0.6 ± 2.9 mmol/l; HBA1c: –1.4 ± 1.1 % and –0.6 ± 1.4 %; Body Weight: –11.4 ± 4 kg and –1.8 ± 3.8 kg; BMI: –4.1 ± 1.3 kg/m_ and –0.7 ± 1.3 kg/m_. Large changes in blood glucose levels were seen immediately.
Conclusion: A low-carbohydrate diet is an effective tool in the treatment of obese patients with type 2 diabetes.
Michal M. Poplawski et al. Reversal of Diabetic Nephropathy by a Ketogenic Diet. PLoS ONE 2011.
Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but fewinterventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be
Daly ME et al. Short-term effects of severe dietary carbohydrate-restriction advice in Type 2 diabetes--a randomized controlled trial. Diabet Med. 2006 Jan;23(1):15-20.
OBJECTIVE: This study sought to examine the effects of a 3-month programme of dietary advice to restrict carbohydrate intake compared with reduced-portion, low-fat advice in obese subjects with poorly controlled Type 2 diabetes.
RESEARCH DESIGN AND METHODS: One hundred and two patients with Type 2 diabetes were recruited across three centres and randomly allocated to receive group education and individual dietary advice. Weight, glycaemic control, lipids and blood pressure were assessed at baseline and 3 months. Dietary quality was assessed at the end of study.
RESULTS: Weight loss was greater in the low-carbohydrate (LC) group (-3.55 +/- 0.63, mean +/- sem) vs. -0.92 +/- 0.40 kg, P = 0.001) and cholesterol : high-density lipoprotein (HDL) ratio improved (-0.48 +/- 0.11 vs. -0.10 +/- 0.10, P = 0.01). However, relative saturated fat intake was greater (13.9 +/- 0.71 vs. 11.0 +/- 0.47% of dietary intake, P < 0.001), although absolute intakes were moderate.
CONCLUSIONS: Carbohydrate restriction was an effective method of achieving short-term weight loss compared with standard advice, but this was at the expense of an increase in relative saturated fat intake.
Eric C Westman et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutrition & Metabolism 2008, 5:36.
Objective: Dietary carbohydrate is the major determinant of postprandial glucose levels, and several clinical studies have shown that low-carbohydrate diets improve glycemic control. In this study, we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus.
Research design and methods: Eighty-four community volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate, ketogenic diet (<20 g of carbohydrate daily; LCKD) or a low-glycemic, reduced-calorie diet (500 kcal/day deficit from weight maintenance diet; LGID). Both groups received group meetings, nutritional supplementation, and an exercise recommendation. The main outcome was glycemic control, measured by hemoglobin A1c.
Results: Forty-nine (58.3%) participants completed the study. Both interventions led to improvements in hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group had greater improvements in hemoglobin A1c ( 1.5% vs. -0.5%, p = 0.03), body weight (-11.1 kg vs. -6.9 kg, p = 0.008), and high density lipoprotein cholesterol (+5.6 mg/dL vs. 0 mg/dL, p < 0.001) compared to the LGID group. Diabetes medications were reduced or eliminated in 95.2% of LCKD
vs. 62% of LGID participants (p < 0.01).
Conclusion: Dietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes. The diet lower in carbohydrate led to greater improvements in glycemic control, and more frequent medication reduction/ elimination than the low glycemic index diet. Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes.
Diet and Training
Jørn Wulff Helge. Adaptation to a Fat-Rich Diet. Effects on Endurance Performance in Humans. Sports Med 2000.
The focus of this review is on studies where dietary fat content was manipulated to investigate the potential ergogenic effect of fat loading on endurance exercise performance. Adaptation to a fat-rich diet is influenced by several factors, of which the duration of the adaptation period, the exercise intensity of the performance test and the content of fat and carbohydrate in the experimental diet are the most important. Evidence is presented that short term adaptation, <6 days, to a fat-rich diet is detrimental to exercise performance. When adaptation to a fat-rich diet was performed over longer periods, studies where performance was tested at moderate intensity, 60 to 80% of maximal oxygen uptake, demonstrate either no difference or an attenuated performance after consumption of a fat-rich compared with a carbohydrate-rich diet. When performance was measured at high intensity after a longer period of adaptation, it was at best maintained, but in most cases attenuated, compared with consuming a carbohydrate-rich diet. Furthermore, evidence is presented that adaptation to a fat-rich diet leads to an increased capacity of the fat oxidative system and an enhancement of the fat supply and subsequently the amount of fat oxidised during exercise. However, in most cases muscle glycogen storage is compromised, and although muscle glycogen breakdown is diminished to a certain extent, this is probably part of the explanation for the lack of performance enhancement after adaptation to a fat-rich diet.
Grant D. Brinkworth et al. Effects of a Low Carbohydrate Weight Loss Diet on Exercise Capacity and Tolerance in Obese Subjects. Obesity (2009) 17, 1916–1923.
Dietary restriction and increased physical activity are recommended for obesity treatment. Very low carbohydratediets are used to promote weight loss, but their effects on physical function and exercise tolerance in overweight andobese individuals are largely unknown. The aim of this study was to compare the effects of a very low carbohydrate,high fat (LC) diet with a conventional high carbohydrate, low fat (HC) diet on aerobic capacity, fuel utilization duringsubmaximal exercise, perceived exercise effort (RPE) and muscle strength. Sixty subjects (age: 49.2 ± 1.2 years; BMI:33.6 ± 0.5 kg/m2) were randomly assigned to an energy restricted (~6–7 MJ, 30% deficit), planned isocaloric LC or HCfor 8 weeks. At baseline and week 8, subjects performed incremental treadmill exercise to exhaustion and handgripand isometric knee extensor strength were assessed. Weight loss was greater in LC compared with HC (8.4 ± 0.4%and 6.7 ± 0.5%, respectively; P = 0.01 time × diet). Peak oxygen uptake and heart rate were unchanged in both groups(P > 0.17). Fat oxidation increased during submaximal exercise in LC but not HC (P < 0.001 time × diet effect).On both diets, perception of effort during submaximal exercise and handgrip strength decreased (P ≤ 0.03 for time),but knee extensor strength remained unchanged (P > 0.25). An LC weight loss diet shifted fuel utilization towardgreater fat oxidation during exercise, but had no detrimental effect on maximal or submaximal markers of aerobicexercise performance or muscle strength compared with an HC diet. Further studies are required to determine theinteraction of LC diets with regular exercise training and the long-term health effects.
Matthew Erlenbusch et al. Effect of High-Fat or High-Carbohydrate Dietson Endurance Exercise: A Meta-Analysis. IntJour of SpoNutr and ExerMeta, 2005, 15, 1-14.
The purpose of this investigation was to clarify, via a meta-analysis, whether the literature favors a high-fat or a high-carbohydrate diet to yield superior endurance exercise performance. Twenty published trials were analyzed to compare exercise performance under different diets. The average effect size of –0.60 indicated that subjects following a high-carbohydrate diet exercised longer until exhaustion. The training status of subjects (trained vs. untrained) was significantly related to effect size (r = –0.576, P < 0.01) and effect sizes separated between trained and untrained subjects were –0.05 and –2.84 respectively. The test for homogeneity revealed significant heterogeneity among effect sizes (χ2  = 43.30, P < 0.05), indicating all of the trials are not describing the same effect. Given this significant heterogeneity, a conclusive endorsement of a high-carbohydrate diet based on the literature is difficult to make. Highly dissimilar trial protocols are the primary reason for heterogeneity.
David S. Rowlands et al. Effects of High-Fat and High-Carbohydrate Diets on Metabolism and Performance in Cycling. Metabolism, Vol 51, No 6 (June), 2002: pp 678-690.
We compared the effects of high-fat and high-carbohydrate dietary conditions on metabolism and short- and ultra-endurance cycling performance. Seven cyclists (V˙ O2max 72 7 mL kg-1 min-1) underwent a 2-week adaptation to each of the following 3 diets: 14-day high carbohydrate with 70 9 percent energy (%E) carbohydrate, 16 5%E fat, and 14 2%E protein; 14-day high fat with 66 10%E fat, 20 3%E protein, and 15 4%E carbohydrate; and 11.5-day high-fat diet followed by 2.5-day carbohydrate-loading. The conditions included a pre-exercise meal of the same composition as the preceding diet. Each diet condition was preceded by a 2-week standardizing normal diet. The exercise test lasted approximately 5 hours and comprised a 15-minute trial, an incremental test to measure the peak fat-oxidation rate, and a 100-km trial. Sports bars and a 5% carbohydrate solution were ingested during the tests. The diets had no statistically significant effect on 15-minute performance, although the high-fat condition tended to reduce distance covered by -2.4% (95% confidence interval: -5.4% to 0.6%, P .11) relative to the fat with carbo-loading condition. In the 100-km time trial, the high-fat and the fat with carbohydrateloading conditions attenuated the decline in power output observed in the high-carbohydrate condition (P .03 to .07), although the corresponding improvement in performance time of 3% to 4% (-2% to 10%) was not statistically significant (P.16 to .22). Power output during the final 5 km of the time trial in the fat with carbo-loading condition was 1.3-fold (1.0 to 1.6, P .04) greater than in the high-carbohydrate condition. Overall, for every 10%E increase in dietary fat, 100-km mean power increased by 2% (-0.0% to 4%, P .06). Relative to the high-carbohydrate condition, the high-fat conditions resulted in the following metabolic changes consistent with greater lipolysis and fuel availability: lower plasma insulin concentration before exercise (P < .0001), and during exercise a 10% to 20% higher plasma-glucose concentration (P < .01), higher plasma glycerol (P < .05), and a 2.5-fold to 2.9-fold increase in the peak fat-oxidation rate (P < .0001). In conclusion, high-fat dietary conditioning increased fat oxidation, and although the main effects were not statistically significant, there was some evidence for enhanced ultra-endurance cycling performance relative to high-carbohydrate.
Wee Kian Yeo et al. Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans. J Appl Physiol. 2008 Nov;105(5):1519-26.
We have previously reported that 5 days of a high-fat diet followed by 1 day of high-carbohydrate intake (Fat-adapt) increased rates of fat oxidation and decreased rates of muscle glycogenolysis during submaximal cycling compared with consumption of an isoenergetic high-carbohydrate diet (HCHO) for 6 days (Burke et al. J Appl Physiol 89: 2413-2421, 2000; Stellingwerff et al. Am J Physiol Endocrinol Metab 290: E380-E388, 2006). To determine potential mechanisms underlying shifts in substrate selection, eight trained subjects performed Fat-adapt and HCHO. On day 7, subjects performed 1-h cycling at 70% peak O2 uptake. Muscle biopsies were taken immediately before and after exercise. Resting muscle glycogen content was similar between treatments, but muscle triglyceride levels were higher after Fat-adapt (P < 0.05). Resting AMPK-alpha1 and -alpha2 activity was higher after Fat-adapt (P = 0.02 and P = 0.05, respectively), while the phosphorylation of AMPK's downstream target, acetyl-CoA carboxylase (pACC at Ser221), tended to be elevated after Fat-adapt (P = 0.09). Both the respiratory exchange ratio (P < 0.01) and muscle glycogen utilization (P < 0.05) were lower during exercise after Fat-adapt. Exercise increased AMPK-alpha1 activity after HCHO (P = 0.03) but not Fat-adapt. Exercise was associated with an increase in pACC at Ser221 for both dietary treatments (P < 0.05), with postexercise pACC Ser221 higher after Fat-adapt (P = 0.02). In conclusion, compared with HCHO, Fat-adapt increased resting muscle triglyceride stores and resting AMPK-alpha1 and -alpha2 activity. Fat-adapt also resulted in higher rates of whole body fat oxidation, reduced muscle glycogenolysis, and attenuated the exercise-induced rise in AMPK-alpha1 and AMPK-alpha2 activity compared with HCHO. Our results demonstrate that AMPK-alpha1 and AMPK-alpha2 activity and fuel selection in skeletal muscle in response to exercise can be manipulated by diet and/or the interactive effects of diet and exercise training.
Wee Kian Yeo et al. Fat adaptation in well-trained athletes: effects on cell metabolism. Appl. Physiol. Nutr. Metab. 36: 12–22 (2011).
The performance of prolonged (>90 min), continuous, endurance exercise is limited by endogenous carbohydrate (CHO) stores. Accordingly, for many decades, sports nutritionists and exercise physiologists have proposed a number of diet training strategies that have the potential to increase fatty acid availability and rates of lipid oxidation and thereby attenuate the rate of glycogen utilization during exercise. Because the acute ingestion of exogenous substrates (primarily CHO) during exercise has little effect on the rates of muscle glycogenolysis, recent studies have focused on short-term (<1–2 weeks) diet-training interventions that increase endogenous substrate stores (i.e., muscle glycogen and lipids) and alter patterns of substrate utilization during exercise. One such strategy is ‘‘fat adaptation’’, an intervention in which welltrained endurance athletes consume a high-fat, low-CHO diet for up to 2 weeks while undertaking their normal training and then immediately follow this by CHO restoration (consuming a high-CHO diet and tapering for 1–3 days before a major endurance event). Compared with an isoenergetic CHO diet for the same intervention period, this ‘‘dietary periodization’’ protocol increases the rate of whole-body and muscle fat oxidation while attenuating the rate of muscle glycogenolysis during submaximal exercise. Of note is that these metabolic perturbations favouring the oxidation of fat persist even in the face of restored endogenous CHO stores and increased exogenous CHO availability. Here we review the current knowledge of some of the potential mechanisms by which skeletal muscle sustains high rates of fat oxidation in the face of high exogenous and endogenous CHO availability.
Theodore W. Zderic et al. High-fat diet elevates resting intramuscular triglyceride concentration and whole body lipolysis during exercise. Am J Physiol Endocrinol Metab 286: E217–E225, 2004.
This study determined the role of intramuscular triglyceride (IMTG) and adipose lipolysis in the elevated fat oxidation during exercise caused by a high-fat diet. In four separate trials, six endurance-trained cyclists exercised at 50% peak O2 consumption for 1 h after a two-day control diet (22% fat, CON) or an isocaloric high-fat diet (60% fat, HF) with or without the ingestion of acipimox, an adipose lipolysis inhibitor, before exercise. During exercise, HF elevated fat oxidation by 72% and whole body lipolysis [i.e., the appearance rate of glycerol in plasma (Ra glycerol)] by 79% compared with CON (P < 0.05), and this was associated with a 36% increase (P < 0.05) in preexercise IMTG concentration. Although acipimox lowered plasma free fatty acid (FFA) availability, HF still increased fat oxidation and Ra glycerol to the same magnitude above control as the increase caused by HF without acipimox (i.e., both increased fat oxidation 13-14 micromol.kg(-1).min(-1)). In conclusion, the marked increase in fat oxidation after a HF diet is associated with elevated IMTG concentration and whole body lipolysis and does not require increased adipose tissue lipolysis and plasma FFA concentration during exercise. This suggests that altered substrate storage in skeletal muscle is responsible for increased fat oxidation during exercise after 2 days of an HF diet.
Jeff S Volek et al. Low-Carbohydrate Diets Promote a More Favorable Body Composition Than Low-Fat Diets. Strength and Conditioning Journal 2010.
A PRIMARY CONCERN WITH CONVENTIONAL WEIGHT LOSS APPROACHES IS THE LOSS OF LEAN BODY MASS THAT OCCURS WHEN FAT MASS IS DECREASED. CONSUMING MODERATEP ROTEIN, WHILE RESTRICTING CARBOHYDRATE, ALLOWS FOR GREATER PRESERVATION OF LEAN BODY MASS. A LOW-CARBOHYDRATE DIET IN CONJUNCTION WITH PERIODIZED RESISTANCE TRAINING PROMOTES GREATER FAT LOSS WHILE PRESERVING LEAN BODY MASS AND PROMOTING ROBUST IMPROVEMENTS IN METABOLIC HEALTH.
Sandra J Peters et al. Metabolic aspects of low carbohydrate diets and exercise. Nutrition & Metabolism 2004, 1:7.
Following a low carbohydrate diet, there is a shift towards more fat and less carbohydrate oxidation to provide energy to skeletal muscle, both at rest and during exercise. This review summarizes recent work on human skeletal muscle carbohydrate and fat metabolic adaptations to a low carbohydrate diet, focusing mainly on pyruvate dehydrogenase and pyruvate dehydrogenase kinase, and how these changes relate to the capacity for carbohydrate oxidation during exercise.
Stephen D Phinney. Ketogenic diets and physical performance. Nutrition & Metabolism 2004, 1:2.
Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.
Jørn Wulff Helge. Long-term fat diet adaptation effects on performance, training capacity, and fat utilization.Med Sci Sports Exerc. 2002 Sep;34(9):1499-504.
It is well known that adaptation to a fat-rich carbohydrate-poor diet results in lower resting muscle glycogen content and a higher rate of fat oxidation during exercise when compared with a carbohydrate-rich diet. The net effect of such an adaptation could potentially be a sparing of muscle glycogen, and because muscle glycogen storage is coupled to endurance performance, it is possible that adaptation to a high-fat diet potentially could enhance endurance performance. Therefore, the first issue in this review is to critically evaluate the available evidence for a potential endurance performance enhancement after long-term fat-rich diet adaptation. Attainment of optimal performance is among other factors dependent also on the quality and quantity of the training performed. When exercise intensity is increased, there is an increased need for carbohydrates. On the other hand, consumption of a fat-rich diet decreases the storage of glycogen in both muscle and liver. Therefore, training intensity may be compromised in individuals while consuming a fat-rich diet. During submaximal exercise, fat for oxidation in muscle is recruited from plasma fatty acids, plasma triacylglycerol, and muscle triacylglycerol: the final question addressed in this review is which of these source(s) of fat contributes to the increased oxidation of fat during submaximal exercise after long-term fat diet adaptation.
Pal T Jabekk et al. Resistance training in overweight women on a ketogenic diet conserved lean body mass while reducing body fat. Nutr Metab (Lond). 2010 Mar 2;7:17.
BACKGROUND: The aim of the present study was to compare the effects of 10 weeks resistance training in combination with either a regular diet (Ex) or a low carbohydrate, ketogenic diet (Lc+Ex) in overweight women on body weight and body composition.
METHODS: 18 untrained women between 20 and 40 years with BMI >/= 25 kg*m-2 were randomly assigned into the Ex or Lc+Ex group. Both groups performed 60-100 min of varied resistance exercise twice weekly. Dietary estimates were based on two 4-day weighed records. Body composition was estimated using Dual Energy X-ray Absorptiometry. Fasting blood samples were analyzed for total-, HDL- and LDL-cholesterol, triacylglycerols, and glucose.
RESULTS: 16 subjects were included in the analyses. Percentage of energy (En%) from carbohydrates, fat and protein was 6, 66, and 22 respectively in the (Lc+Ex) group and 41, 34, 17 in the Ex group. Mean weight change (pre-post) was -5.6 +/- 2.6 kg in Lc+Ex; (p < 0.001) and 0.8 +/- 1.5 kg in Ex; (p = 0.175). The Lc+Ex group lost 5.6 +/- 2.9 kg of fat mass (p = 0.001) with no significant change in lean body mass (LBM), while the Ex group gained 1.6 +/- 1.8 kg of LBM (p = 0.045) with no significant change in fat mass (p = 0.059). Fasting blood lipids and blood glucose were not significantly affected by the interventions.
CONCLUSION: Resistance exercise in combination with a ketogenic diet may reduce body fat without significantly changing LBM, while resistance exercise on a regular diet may increase LBM in without significantly affecting fat mass. Fasting blood lipids do not seem to be negatively influenced by the combination of resistance exercise and a low carbohydrate diet.
Irritable Bowel Syndrome
Eric C. Westman et al. A Very Low-Carbohydrate Diet Improves Symptoms and Quality of Life in Diarrhea-Predominant Irritable Bowel Syndrome. Clinical Gastroenterology and Hepatology 2009.
Background & Aims: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This study prospectively evaluated a VLCD in IBS-D.
Methods: Participants with moderate to severe IBS-D were provided a 2-week standard diet, then 4 weeks of a VLCD (20 g carbohydrates/d). A responder was defined as having adequate relief of gastrointestinal symptoms for 2 or more weeks during the VLCD. Changes in abdominal pain, stool habits, and quality of life also were measured.
Results: Of the 17 participants enrolled, 13 completed the study and all met the responder definition, with 10 (77%) reporting adequate relief for all 4 VLCD weeks. Stool frequency decreased (2.6 ± 0.8/d to 1.4 ± 0.6/d; P < .001). Stool consistency improved from diarrheal to normal form (Bristol Stool Score, 5.3 ± 0.7 to 3.8 ± 1.2; P < .001). Pain scores and quality-of-life measures significantly improved. Outcomes were independent of weight loss.
Conclusions: A VLCD provides adequate relief, and improves abdominal pain, stool habits, and quality of life in IBS-D.
Mood and Cognitive performance
Grant D. Brinkworth et al. Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function. Arch Intern Med. 2009;169(20):1873-1880.
Background: Very low-carbohydrate (LC) diets are often used to promote weight loss, but the long-term effects
on psychological function remain unknown.
Methods: A total of 106 overweight and obese participants (mean [SE] age, 50.0 [0.8] years; mean [SE] body mass index [calculated as weight in kilograms divided by height in meters squared], 33.7 [0.4]) were randomlyassigned either to an energy-restricted (approximately 1433- 1672 kcal [to convert to kilojoules, multiply by 4.186]), planned isocaloric, very low-carbohydrate, high-fat (LC) diet or to a high-carbohydrate, low-fat (LF) diet for 1 year. Changes in body weight, psychological mood and wellbeing (Profile of Mood States, Beck Depression Inventory, and Spielberger State Anxiety Inventory scores), and cognitive functioning (working memory and speed of processing) were assessed.
Results: By 1 year, the overall mean (SE) weight loss was 13.7 (1.8) kg, with no significant difference between groups (P=.26). Over the course of the study, there were significant time diet interactions for Spielberger State Anxiety Inventory, Beck Depression Inventory, and Profile of Mood States scores for total mood disturbance, anger-hostility, confusion-bewilderment, and depression-dejection (P.05) as a result of greater improvements in these psychological mood states for the LF diet compared with the LC diet. Working memory improved by 1 year (P.001 for time), but speed of processing remained largely unchanged, with no effect of diet composition on either cognitive domain.
Conclusions: Over 1 year, there was a favorable effect of an energy-restricted LF diet compared with an isocaloric LC diet on mood state and affect in overweight and obese individuals. Both diets had similar effects on working memory and speed of processing.
Angela K Halyburton et al. Low- and high-carbohydrate weight-loss diets have similar effects on mood but not cognitive performance. Am J Clin Nutr 2007;86:580 –7.
Background: Low-carbohydrate diets are often used to promote weight loss, but their effects on psychological function are largely unknown.
Objective: Wecompared the effects of a low-carbohydrate, high-fat (LCHF) diet with a conventional high-carbohydrate, low-fat (HCLF) diet on mood and cognitive function.
Design: Ninety-three overweight or obese participants [x SEM age: 50.2 0.8 y; body mass index (in kg/m2): 33.6 0.4] were randomly assigned to an energy-restricted (6–7 MJ, 30% deficit), planned isocaloricLCHFdiet or an HCLFdiet for 8 wk. Body weight and psychological well-being were measured by using the Profile of Mood States, Beck Depression Inventory, and Spielberger State Anxiety Inventory instruments at baseline and fortnightly. Cognitive functioning (working memory and speed of processing) was assessed at baseline and week 8.
Results: The LCHF diet resulted in significantly greater weight loss than did the HCLF diet (7.8 0.4 and 6.4 0.4 kg, respectively; P 0.04). Both groups showed improvements in psychological well-being (P 0.01 for time), with the greatest effect occurring during the first 2 wk, but there was no significant difference between groups. There were no significant between-group differences in working memory (P0.68), but there was a significant timediet interaction for speed of processing (P 0.04), so that this measure improved less in the LCHF than in the HCLF diet group.
Conclusions: Both dietary patterns significantly reduced body weight and were associated with improvements in mood. There was some evidence for a smaller improvement in cognitive functioning with the LCHF diet with respect to speed of processing, but further studies are required to determine the replicability of this finding.
Eric H. Kossoff et al. A prospective study of the modified Atkins diet for intractable epilepsy in adults. Epilepsia, 49(2):316–319, 2008.
Purpose: The ketogenic diet is not typically offered to adults with epilepsy due to the significant lifestyle alterations needed for its use. The modified Atkins diet has been recently demonstrated to be therapeutic for children without the need for an admission, fasting period, weighing of foods, or fluid, calorie, and protein restriction.
Methods: A prospective, open-label study was performed of adults over 18 years of age, having at least weekly seizures and prior use of at least two anticonvulsants. Carbohydrates were initially restricted to 15 g/day, fats were encouraged, and fluids, protein, and calories were allowed ad lib.
Results: Thirty patients, with age ranging from 18 to 53 years, were enrolled. Using an intent-to-treat analysis, 47% had a >50% seizure reduction after 1 and 3 months on the diet; 33% after 6 months. In those with seizure reduction, the median time to improvement was 2 weeks (range: 1–8 weeks). The mean weight loss was 6.8 kg, p < 0.001. Body-mass index (BMI) decrease correlated with efficacy at 3months,p=0.03. Ten subjects (30%) discontinued the diet prior to 3 months. Side effects included increased cholesterol (mean 187 to 201 mg/dL), blood urea nitrogen (BUN; 13 to 16 mg/dL), and urine calcium to creatinine ratio (0.14 to 0.19).
Conclusions: A modified Atkins diet appears to demonstrate preliminary efficacy for adults with intractable epilepsy, especially in those who lost weight. Considering the rapid response in those who improved, but somewhat high discontinuation rate, a 2-month trial period may be adequate to assess for efficacy.
Adam L. Hartman et al. Clinical Aspects of the Ketogenic Diet. Epilepsia, 48(1):31–42, 2007.
The ketogenic diet remains a valuable therapeutic option for patients with intractable epilepsy. Clinical aspects of the diet’s success may provide insights into epileptogenesis and anticonvulsant action. The diet’s efficacy has been established primarily through large case series. The diet has been used successfully in patients with many different epilepsy syndromes in countries around the world. Potential adverse effects can be avoided with careful attention during the diet’s initiation and maintenance phases. In the last decade, variations to the classical ketogenic diet have been utilized. Ketogenic diets now are being used for diseases other than epilepsy. This critical analysis of the diet should provide the impetus for further clinical and basic research into the diet’s application and mechanisms of action.
Seyed Hassan Tonekaboni et al. Efcacy of the Atkins Diet as Therapy for Intractable Epilepsy in Children. Archives of Iranian Medicine, Volume 13, Number 6, November 2010.
Background and Aims: The ketogenic diet is an effective medical therapy for intractable childhood epilepsy. However, it has drawbacks in that it restricts calories, uids and protein. The Atkins diet may also induce ketosis without those restrictions. Our objective was to evaluate the efcacy of a modied Atkins diet in children with intractable childhood epilepsy.
Methods: This clinical trial was conducted in 51 epileptic children aged 1 – 16 years with refractory seizures from Feb. 2004 to Oct. 2006. Outcome measures included seizure frequency and adverse reactions. Twenty-seven patients left the study for various reasons, leaving 24 who continued the Atkins diet for a minimum of three months. Carbohydrates were initially limited to 10g/day and fats constituted 60% of the total energy requirement. All participants received vitamin and calcium supplementation.
Results: Following three months of treatment with the Atkins diet, 16 patients (67%) had >50% decrease in seizure frequency, and 6 (25%) had >90% improvement, of whom 5 were seizure-free. Mean seizure frequency after the rst, second and third months of treatment were signicantly lower than at baseline (P values <0.001, 0.001 and 0.002, respectively).
Conclusion: The Atkins diet can be considered as a safe and effective alternative therapy for intractable childhood epilepsy. Atkins diet was well tolerated in our patients with rare complications and it appears to demonstrate preliminary efcacy in childhood refractory epilepsy.
Helen Truby et al. Commercial weight loss diets meet nutrient requirements in free living adults over 8 weeks: A randomised controlled weight loss trial. Nutrition Journal 2008, 7:25.
Objective: To investigate the effect of commercial weight loss programmes on macronutrient composition and micronutrient adequacy over a 2 month period.
Design: Adults were randomly allocated to follow the Slim Fast Plan, Weight Watchers Pure Points Programme, Dr Atkins' New Diet Revolution, or Rosemary Conley's "Eat Yourself Slim" Diet & Fitness Plan.
Setting: A multi-centre randomised controlled trial.
Subjects: 293 adults, mean age 40.3 years and a mean BMI 31.7 (range 27–38) were allocated to follow one of the four diets or control group. Subjects completed a 7-day food and activity diary at baseline (prior to randomisation) and after 2 months. Diet records were analysed for nutrient composition using WinDiets (research version).
Result: A significant shift in the macronutrient composition of the diet with concurrent alteration of the micronutrient profile was apparent with all diets. There was no evidence to suggest micronutrient deficiency in subjects on any of the dietary regimens. However, those sub-groups with higher needs for specific micronutrients, such as folate, iron or calcium may benefit from tailored dietary advice.
Conclusion: The diets tested all resulted in considerable macronutrient change and resulted in an energy deficit indicating dietary compliance. Health professionals and those working in community and public health should be reassured of the nutritional adequacy of the diets tested.
Frederick F. Samaha et al. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. N Engl J Med 2003;348:2074-81.
Background: The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed.
Methods: We randomly assigned 132 severely obese subjects (including 77 blacks and 23 women) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and fat-restricted (low-fat) diet.
Results: Seventy-nine subjects completed the six-month study. An analysis including all subjects, with the last observation carried forward for those who dropped out, showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet (mean [±SD], –5.8±8.6 kg vs. –1.9±4.2 kg; P=0.002) and had greater decreases in triglyceride levels (mean, –20±43 percent vs. –4±31 percent; P=0.001), irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications. Insulin sensitivity, measured only in subjects without diabetes, also improved more among subjects on the low-carbohydrate diet (6±9 percent vs. –3±8 percent, P=0.01). The amount of weight lost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01) were independent predictors of improvement in triglyceride levels and insulin sensitivity.
Conclusions: Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorieand fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed.
William S. Yancy. A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia. Ann Intern Med. 2004;140:769-777.
Background: Low-carbohydrate diets remain popular despite a paucity of scientific evidence on their effectiveness.
Objective: To compare the effects of a low-carbohydrate, ketogenic diet program with those of a low-fat, low-cholesterol, reduced-calorie diet.
Design: Randomized, controlled trial.
Setting: Outpatient research clinic.
Participants: 120 overweight, hyperlipidemic volunteers from the community.
Intervention: Low-carbohydrate diet (initially, <20 g of carbohydrate daily) plus nutritional supplementation, exercise recommendation, and group meetings, or low-fat diet (<30% energy from fat, <300 mg of cholesterol daily, and deficit of 500 to 1000 kcal/d) plus exercise recommendation and group meetings.
Measurements: Body weight, body composition, fasting serum lipid levels, and tolerability.
Results: A greater proportion of the low-carbohydrate diet group than the low-fat diet group completed the study (76% vs. 57%; P 0.02). At 24 weeks, weight loss was greater in the lowcarbohydrate diet group than in the low-fat diet group (mean change, 12.9% vs. 6.7%; P < 0.001). Patients in both groups lost substantially more fat mass (change, 9.4 kg with the lowcarbohydrate diet vs. 4.8 kg with the low-fat diet) than fat-free mass (change, 3.3 kg vs. 2.4 kg, respectively). Compared with recipients of the low-fat diet, recipients of the low-carbohydrate diet had greater decreases in serum triglyceride levels (change, 0.84 mmol/L vs. 0.31 mmol/L [74.2 mg/dL vs. 27.9 mg/dL]; P 0.004) and greater increases in high-density lipoprotein cholesterol levels (0.14 mmol/L vs. 0.04 mmol/L [5.5 mg/dL vs.
1.6 mg/dL]; P < 0.001). Changes in low-density lipoprotein cholesterol level did not differ statistically (0.04 mmol/L [1.6mg/dL] with the low-carbohydrate diet and 0.19 mmol/L [7.4mg/dL] with the low-fat diet; P 0.2). Minor adverse effectswere more frequent in the low-carbohydrate diet group.
Limitations: We could not definitively distinguish effects of the low-carbohydrate diet and those of the nutritional supplements provided only to that group. In addition, participants were healthy and were followed for only 24 weeks. These factors limit the generalizability of the study results.
Conclusions: Compared with a low-fat diet, a low-carbohydrate diet program had better participant retention and greater weight loss. During active weight loss, serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low-carbohydrate diet than with the low-fat diet.
Gary D. Foster. A Randomized Trial of a Low-Carbohydrate Diet for Obesity. N Engl J Med 2003.
Background: Despite the popularity of the low-carbohydrate, high-protein, high-fat (Atkins) diet, no randomized, controlled trials have evaluated its efficacy.
Methods: We conducted a one-year, multicenter, controlled trial involving 63 obese men and women who were randomly assigned to either a low-carbohydrate, high-protein, high-fat diet or a low-calorie, high-carbohydrate, low-fat (conventional) diet. Professional contact was minimal to replicate the approach used by most dieters.
Results: Subjects on the low-carbohydrate diet had lost more weight than subjects on the conventional diet at 3 months (mean [±SD], ¡6.8±5.0 vs. ¡2.7±3.7 percent of body weight;P=0.001) and 6 months (¡7.0±6.5 vs. ¡3.±5.6 percent of body weight, P=0.02), but the difference at 12 months was not significant (¡4.4±6.7 vs. ¡2.5±6.3 percent of body weight, P=0.26). After three months, no significant differences were found between the groups in total or low-density lipoprotein cholesterol concentrations. The increase in high-density lipoprotein cholesterol concentrations and the decrease in triglyceride concentrations were greater among subjects on the low-carbohydrate diet than among
those on the conventional diet throughout most of the study. Both diets significantly decreased diastolic blood pressure and the insulin response to an oral glucose load.
Conclusions: The low-carbohydrate diet produced a greater weight loss (absolute difference, approximately 4percent) than did the conventional diet for the first six months, but the differences were not significant at one year. The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease. Adherence was poor and attrition was high in both groups. Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate, high-protein, high-fat diets.
James D LeCheminant et al. Comparison of a low carbohydrate and low fat diet for weight maintenance in overweight or obese adults enrolled in a clinical weight management program. Nutrition Journal 2007, 6:36.
Background: Recent evidence suggests that a low carbohydrate (LC) diet may be equally or more effective for short-term weight loss than a traditional low fat (LF) diet; however, less is known about how they compare for weight maintenance. The purpose of this study was to compare body weight (BW) for participants in a clinical weight management program, consuming a LC or LF weight maintenance diet for 6 months following weight loss.
Methods: Fifty-five (29 low carbohydrate diet; 26 low fat diet) overweight/obese middle-aged adults completed a 9 month weight management program that included instruction for behavior, physical activity (PA), and nutrition. For 3 months all participants consumed an identical liquid diet (2177 kJ/day) followed by 1 month of re-feeding with solid foods either low in carbohydrate or low in fat. For the remaining 5 months, participants were prescribed a meal plan low in dietary carbohydrate (~20%) or fat (~30%). BW and carbohydrate or fat grams were collected at each group meeting. Energy and macronutrient intake were assessed at baseline, 3, 6, and 9 months.
Results: The LC group increased BW from 89.2 ± 14.4 kg at 3 months to 89.3 ± 16.1 kg at 9 months (P = 0.84). The LF group decreased BW from 86.3 ± 12.0 kg at 3 months to 86.0 ± 14.0 kg at 9 months (P = 0.96). BW was not different between groups during weight maintenance (P = 0.87). Fifty-five percent (16/29) and 50% (13/26) of participants for the LC and LF groups, respectively, continued to decrease their body weight during weight maintenance.
Conclusion: Following a 3 month liquid diet, the LC and LF diet groups were equally effective for BW maintenance over 6 months; however, there was significant variation in weight change within each group.
Jeff S. Volek et al. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutrition & Metabolism 2004, 1:13.
Objective: To compare the effects of isocaloric, energy-restricted very low-carbohydrate ketogenic (VLCK) and low-fat (LF) diets on weight loss, body composition, trunk fat mass, and resting energy expenditure (REE) in overweight/obese men and women.
Design: Randomized, balanced, two diet period clinical intervention study. Subjects were prescribed two energy-restricted (-500 kcal/day) diets: a VLCK diet with a goal to decrease carbohydrate levels below 10% of energy and induce ketosis and a LF diet with a goal similar to national recommendations (%carbohydrate:fat:protein = ~60:25:15%). Subjects: 15 healthy, overweight/obese men (mean ± s.e.m.: age 33.2 ± 2.9 y, body mass 109.1 ±
4.6 kg, body mass index 34.1 ± 1.1 kg/m2) and 13 premenopausal women (age 34.0 ± 2.4 y, body mass 76.3 ± 3.6 kg, body mass index 29.6 ± 1.1 kg/m2).
Measurements: Weight loss, body composition, trunk fat (by dual-energy X-ray absorptiometry), and resting energy expenditure (REE) were determined at baseline and after each diet intervention. Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person.
Results: Actual nutrient intakes from food records during the VLCK (%carbohydrate:fat:protein = ~9:63:28%) and the LF (~58:22:20%) were significantly different. Dietary energy was restricted, but was slightly higher during the VLCK (1855 kcal/day) compared to the LF (1562 kcal/day) diet for men. Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss, total fat loss, and trunk fat loss for men (despite significantly greater energy intake). The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss. The greater reduction in trunk fat was not merely due to the greater total fat loss, because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women. Absolute REE (kcal/day) was decreased with both diets as expected, but REE expressed relative to body mass (kcal/kg), was better maintained on the VLCK diet for men only. Individual responses clearly show the majority of men and women experience greater weight and fat loss on a VLCK than a LF diet.
Conclusion: This study shows a clear benefit of a VLCK over LF diet for short-term body weight and fat loss, especially in men. A preferential loss of fat in the trunk region with a VLCK diet is novel and potentially clinically significant but requires further validation. These data provide additional support for the concept of metabolic advantage with diets representing extremes in macronutrient distribution.
Alexandra M Johnstone et al. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am J Clin Nutr 2008;87:44 –55.
Background: Altering the macronutrient composition of the diet influences hunger and satiety. Studies have compared high- and low-protein diets, but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake.
Objective: We aimed to compare the hunger, appetite, and weightloss responses to a high-protein, low-carbohydrate [(LC) ketogenic] and those to a high-protein, medium-carbohydrate [(MC) nonketogenic] diet in obese men feeding ad libitum.
Design: Seventeen obesemenwere studied in a residential trial; food was provided daily. Subjects were offered 2 high-protein (30% of energy) ad libitum diets, each for a 4-wk period—an LC (4% carbohydrate) ketogenic diet and anMC (35% carbohydrate) diet—randomized in a crossover design. Body weight was measured daily, and ketosis was monitored by analysis of plasma and urine samples. Hunger was assessed by using a computerized visual analogue system.
Results: Ad libitum energy intakes were lower with the LC diet than with theMCdiet [P0.02; SE of the difference (SED): 0.27] at 7.25 and 7.95 MJ/d, respectively. Over the 4-wk period, hunger was significantly lower (P 0.014; SED: 1.76) and weight loss was significantly greater (P 0.006; SED: 0.62) with the LC diet (6.34kg) than with theMCdiet (4.35 kg). TheLCdiet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma (P 0.036 from baseline; SED: 0.62) and 2.99 mmol/L in urine (P 0.001 from baseline; SED: 0.36).
Conclusion: In the short term, high-protein, low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein, medium-carbohydrate nonketogenic diets.
Nancy F. Krebs et al. Efficacy and Safety of a High Protein, Low Carbohydrate Diet for Weight Loss in Severely Obese Adolescents. J Pediatr 2010;157:252-8.
Objective: To evaluate the efficacy and safety of a carbohydrate restricted versus a low fat diet on weight loss,metabolic markers, body composition, and cardiac function tests in severely obese adolescents.
Study design: Subjects were randomly assigned to 1 of 2 diets: a high protein, low carbohydrate (20 g/d) diet (highprotein, low carbohydrate, HPLC) or low fat (30% of calories) regimen for 13 weeks; close monitoring was maintainedto evaluate safety. After the intervention, no clinical contact was made until follow-up measurements wereobtained at 24 and 36 weeks from baseline. The primary outcome was change in body mass index Z-score forage and sex (BMI-Z) at 13, 24, and 36 weeks.
Results: Forty-six subjects (24 HPLC, 22 in low fat) initiated and 33 subjects completed the intervention; follow-updata were available on approximately half of the subjects. Significant reduction in (BMI-Z) was achieved in bothgroups during intervention and was significantly greater for the HPLC group (P = .03). Both groups maintained significantBMI-Z reduction at follow-up; changes were not significantly different between groups. Loss of lean bodymass was not spared in the HPLC group. No serious adverse effects were observed related to metabolic profiles,cardiac function, or subjective complaints.
Conclusions: The HPLC diet is a safe and effective option for medically supervised weight loss in severely obeseadolescents.
Clifton PM et al. High protein diets decrease total and abdominal fat and improve CVD risk profile in overweight and obese men and women with elevated triacylglycerol. Nutr Metab Cardiovasc Dis. 2009 Oct;19(8):548-54.
BACKGROUND AND AIMS: It is unclear whether high protein weight loss diets have beneficial effects on weight loss, abdominal fat mass, lipids, glucose and insulin compared to conventional low fat diets in subjects at increased risk of cardiovascular disease (CVD) because of elevated glucose and triglyceride concentrations. Our objective was to determine the effects of high protein (HP) compared to standard protein (SP) diets on CVD risk in obese adults.
METHODS AND RESULTS: Data from three, 12 week, randomized parallel trials with subjects assigned to either HP or SP diet (5500-6500 kJ/day) were pooled. Weight, body composition (dual energy X-ray absorptiometry), lipids, insulin and glucose were measured before and after weight loss. Data from 215 subjects (49.9+/-9.8 years, BMI 33.5+/-3.7 kg/m(2)), 108 HP, 107 SP were analyzed. Weight loss (HP diet 7.82+/-0.37 kg; SP diet 7.65+/-0.39 kg, NS) and total fat loss were not different (HP 6.8+/-4.3 kg; LP 6.4+/-4.7 kg, NS on intention to treat analysis). The reduction in triacylglycerol (TAG) was greater on HP than SP 0.48+/-0.07 mmol/L vs 0.27+/-0.06 mmol/L, (P<0.001). Subjects with TAG greater than the median (>1.54 mmol/L at baseline) lost more weight (HP 8.5+/-0.6; SP 6.9+/-0.6 kg, P=0.01, diet by TG group), total (HP 6.17+/-0.50 kg; SP 4.52+/-0.52 kg, P=0.007) and abdominal fat (HP 1.92+/-0.17 kg; SP 1.23+/-0.19 kg, P=0.005) on HP. Total cholesterol (12 vs 6%, HP vs SP) and TAG (39 vs 20%, HP vs SP) decreased to a greater extent in these subjects (both P</=0.05) on HP.
CONCLUSION: Short-term high protein weight loss diets had beneficial effects on total cholesterol and triacylglycerol in overweight and obese subjects and achieved greater weight loss and better lipid results in subjects at increased risk of CVD. These observations provide further information regarding the utility of this dietary approach in effectively managing body weight and composition and reducing CVD risk in overweight and obese individuals.
Hussein M Dashti- et al. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol 2004;9(3):200-205.
BACKGROUND: Although various studies have examined the short-term effects of a ketogenic diet in reducing weight in obese patients, its long-term effects on various physical and biochemical parameters are not known.
OBJECTIVE: To determine the effects of a 24-week ketogenic diet (consisting of 30 g carbohydrate, 1 g/kg body weight protein, 20% saturated fat, and 80% polyunsaturated and monounsaturated fat) in obese patients.
PATIENTS AND METHODS: In the present study, 83 obese patients (39 men and 44 women) with a body mass index greater than 35 kg/m2, and high glucose and cholesterol levels were selected. The body weight, body mass index, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, fasting blood sugar, urea and creatinine levels were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored after eight, 16 and 24 weeks of treatment.
RESULTS: The weight and body mass index of the patients decreased significantly (P<0.0001). The level of total cholesterol decreased from week 1 to week 24. HDL cholesterol levels significantly increased, whereas LDL cholesterol levels significantly decreased after treatment. The level of triglycerides decreased significantly following 24 weeks of treatment. The level of blood glucose significantly decreased. The changes in the level of urea and creatinine were not statistically significant.
CONCLUSIONS: 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.
Hussein M. Dashti. Long term effects of ketogenic diet in obese subjects with high cholesterol level. Mol Cell Biochem 286: 1–9, 2006.
Objective: Various studies have convincingly shown the beneficial effect of ketogenic diet (in which the daily consumption of carbohydrate is less than 20 grams, regardless of fat, protein and caloric intake) in reducing weight in obese subjects. However, its long term effect on obese subjects with high total cholesterol (as compared to obese subjects with normal cholesterol level) is lacking. It is believed that ketogenic diet may have adverse effect on the lipid profile. Therefore, in this study the effect of ketogenic diet in obese subjects with high cholesterol level above 6 mmol/L is compared to those with normocholesterolemia for a period of 56 weeks.
Materials and methods: In this study, 66 healthy obese subjects with body mass index (BMI) greater than 30, having high cholesterol level (Group I; n = 35) and those subjects with normal cholesterol level (Group II; n = 31) were selected. The body weight, body mass index, total cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, glucose and triglycerides were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored at 8, 16, 24, 32, 40, 48 and 56 weeks of the treatment.
Results: The body weight and body mass index of both groups decreased significantly (P < 0.0001). The level of total cholesterol, LDL cholesterol, triglycerides and blood glucose level decreased significantly (P < 0.0001), whereas HDL cholesterol increased significantly (P < 0.0001) after the treatment in both groups.
Conclusion: This study shows the beneficial effects of ketogenic diet following its long term administration in obese subjects with a high level of total cholesterol. Moreover, this study demonstrates that low carbohydrate diet is safe to use for a longer period of time in obese subjects with a high total cholesterol level and those with normocholesterolemia.
M. Hession et al. Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obesity Reviews (2009) 10, 36–50.
Summary: There are few studies comparing the effects of low-carbohydrate/high-protein diets with low-fat/high-carbohydrate diets for obesity and cardiovascular disease risk. This systematic review focuses on randomized controlled trials of lowcarbohydrate diets compared with low-fat/low-calorie diets. Studies conducted in adult populations with mean or median body mass index of 28 kg m-2 were included. Thirteen electronic databases were searched and randomized controlled trials from January 2000 to March 2007 were evaluated. Trials were included if they lasted at least 6 months and assessed the weight-loss effects of lowcarbohydrate diets against low-fat/low-calorie diets. For each study, data were abstracted and checked by two researchers prior to electronic data entry. The computer program Review Manager 4.2.2 was used for the data analysis. Thirteen articles met the inclusion criteria. There were significant differences between the groups for weight, high-density lipoprotein cholesterol, triacylglycerols and systolic blood pressure, favouring the low-carbohydrate diet. There was a higher attrition rate in the low-fat compared with the low-carbohydrate groups suggesting a patient preference for a low-carbohydrate/high-protein approach as opposed to the Public Health preference of a low-fat/high-carbohydrate diet. Evidence from this systematic review demonstrates that low-carbohydrate/high-protein diets are more effective at 6 months and are as effective, if not more, as low-fat diets in reducing weight and cardiovascular disease risk up to 1 year. More evidence and longer-term studies are needed to assess the long-term cardiovascular benefits from the weight loss achieved using these diets.
Iris Shai et al. Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. N Engl J Med 2008.
Background: Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates.
Methods: In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non–restricted-calorie.
Results: The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001
for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P = 0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels).
Conclusions: Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions.
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