The Ketogenic Diet
There have been anecdotal reports of the efficacy of dietary
therapy, especially starvation, for the treatment of epilepsy
since Biblical times. Clinical and
research interest in the ketogenic diet was renewed in the
early 1990s after a 2-year-old boy with intractable seizures
was treated with the ketogenic diet at the Johns Hopkins
Hospital. The diet is now well established in the
medical community and is even reimbursed by insurance
companies, including Blue Cross and Blue Shield. The main indication for the ketogenic diet is the presence of seizures that are difficult to control, such as those that occur in Lennox-Gastaut syndrome. However, the efficacy of the diet appears to be independent of seizure type.
Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy a Meta-analysis.
Maydell BV, Wyllie E, Akhtar N, et al. Efficacy of the ketogenic diet
in focal versus generalized seizures. Pediatr Neurol. 2001;25:208 –212. Abstract:
Most reports of the ketogenic diet have focused on its efficacy for generalized seizures. Few data are available regarding its effect on focal seizures. We retrospectively studied patients (mean = 7.5 years of age) with medically intractable epilepsy treated by the ketogenic diet. The predominant seizure types in each patient were classified as generalized (100 patients) or focal (34 patients) based on ictal electroencephalograms (EEGs) or seizure semiology and interictal EEG. A seizure reduction of more than 50% compared with baseline was seen in nine patients (27%) with focal seizures and 46 patients (46%) with generalized seizures at 3 months, in 10 patients (30%) with focal seizures and 46 patients (46%) with generalized seizures at 6 months, and in eight patients (24%) with focal seizures and 42 patients (42%) with generalized seizures at 12 months. Differences were not significant. Outcome tended to be better in patients younger than 12 years of age compared with the older age group, but the difference was significant at 6 months only. Our results suggest that some patients with intractable focal epilepsy may respond favorably to the ketogenic diet and that this option should be considered if epilepsy surgery is not possible.
Because the ketogenic diet is associated with major
shifts in cerebral energy metabolism, some authors caution
against using the diet in patients with certain metabolic
disorders. These include pyruvate carboxylase deficiency,
mitochondrial disorders, and fatty acid oxidation problems.
The actual dietary components are individually calculated
for each patient, incorporating both daily calories,
fluids, and the ratio of fat to protein and carbohydrates,
ranging from 2:1 to 4:1, with higher ratios more restrictive. Young children and infants as well as adolescents are typically started on a 3:1 ratio to be able to provide extra protein and to allow adolescents
increased choices of foods. Most other children are
started on a 4:1 ratio. This is treatment for epilepsy. carbohydrates are typically 5 to 10 g/day, with the remainder of calories as fat. Although fluids and calories are traditionally restricted to improve ketosis, there is little evidence regarding the necessity of this. Older children are given computergenerated
menus that offer 3 daily meals and a snack. Fluids are usually also restricted to 80% of daily needs. There are
some data to suggest that the initial period of fasting is not
necessary for long-term ketosis and that the diet can be
initiated at home without hospitalization. Is a Fast Necessary When Initiating the ketogenic diet Acute problems periodically seen during fasting include hypoglycemia, vomiting, dehydration, and food refusal.
The patient’s medications are also reviewed and adjusted
during the admission to make sure that they are free of
carbohydrates as many, especially liquids, have high carbohydrate
content that can interfere with ketosis.
Seizures Decrease Rapidly After Fasting – preliminary studies of the ketogenic diet
Another version of the ketogenic diet, based on
medium-chain triglyceride (MCT) oil, was developed in the
late 1960s.22 The motivation for development of this diet was
that MCT oils are more strongly ketogenic than longer fatty
acids. This reduces the amount of fat that is required in the
diet, allowing a larger amount of protein and even carbohydrates.
This version of diet, however, can cause gastrointestinal
distress in patients (stomach cramps and diarrhea) and is
used now only occasionally. MCT oil is often incorporated in
the classic ketogenic diet for a variety of reasons, including
increasing the protein and carbohydrate allowances, countering
constipation, or improving dyslipidemia. The medium chain triglyceride diet and intractable epilepsy.
Maintenance of the diet is difficult and common culprits of sugar are new medications or food additives that are labeled as “sugar free” but may still contain large amounts of carbohydrates such as maltodextrin, sorbitol, starch, or fructose. If ketones are not 4 or more than 160 mg/dL, then a 24-hour fast with clear liquids can be used to improve ketosis rapidly.
Acidosis is a major concern during both diet initiation and
acute intercurrent illnesses. It is important that the patient and
family understand signs of acidosis and how to hydrate with
carbohydrate-free fluids. Most children on the diet have a low
baseline acidosis, with HCO3 – of 12 to 18 mg/dL. The issue of whether carnitine supplementation should be used (or acylcarnitine levels checked) is still controversial. COmmon symptoms on the diet are:
Nausea/vomiting during initiation
Constipation (classic diet)
Diarrhea (MCT version)
The incidence of renal calculi in children on the ketogenic
diet is 5 to 6%.27,28 The diet can cause hypercalciuria,
urine acidification, and hypocitraturia, increasing the risk of
uric acid and, less commonly, calcium phosphate and oxalate
stones. Increased hydration and oral polycitrates (Polycitra K™, 2 mEq/kg/day divided twice daily) if there is a family or personal history of kidney stones.
Another known side effect is hyperlipidemia.29–31 A
prospective study of children on the classic diet showed
significant elevations of total cholesterol, triglycerides, and
the atherogenic apolipoprotein B containing lipoproteins
(LDL and VLDL). There was a significant reduction of the
antiatherogenic apolipoprotein A-containing lipoproteins
Long-term monitoring of the ketogenic diet
Manipulation of Types of Fats and Cholesterol Intake Can Successfully Improve the Lipid Profile While Maintaining the Efficacy of the Ketogenic Diet
More fat and fewer seizures dietary therapies for epilepsy
Long-term health consequences of epilepsy
Ketogenic Therapies and Recipes Link << Excellent
http://www.hopkinsmedicine.org/neurology_neurosurgery/ < Ketogenic treatment of epilepsy
http://www.calorieking.com/ Calorie counter and Carbohydrate trackers
http://www.myketocal.com/ketocal4-1.aspx Ketogenic diet supplement
Ketocal Supplement PDF guide
Ketogenic Diet Nutritionals
Prospective Study of the Modified Atkins diet and ketogenic supplement during initial month
http://www.atkins.com/ < Atkins Diet resource
Typical day of food for a child on a 4:1 ratio, 1500 calorie ketogenic diet:
Breakfast: Egg with Bacon Egg 28g Bacon 11g 36% heavy whipping cream 37g Butter 23g Apple 9g
Snack: Peanut Butter Ball Peanut Butter 6g Butter 9g
Lunch: Tuna Salad Tuna fish 28g Mayonnaise 30g Celery 10g 36% heavy whipping cream 36g Lettuce 15g Snack: Keto Yogurt 36% heavy whipping cream 18g Sour Cream 17g Strawberries 4g Artificial sweetener (e.g. Splenda™)
Dinner: Cheeseburger Ground beef 22g American cheese 10g Butter 26g Cream 38g Lettuce 10g Green beans 11g Snack: Keto Custard 36% heavy whipping cream 25g Egg 9g Pure vanilla flavoring
Creative Management of the ketogenic diet and diet therapies
Ketogenic diet protocol at Johns Hopkins Hospital
Day prior to admission (Sunday)
• Reduced carbohydrates for 24 hours • Fasting starts the evening before admission
Day 1 (Monday) • Admitted to the hospital • Fasting continues • Fluids restricted to 60–75 mL/kg • Blood glucose monitored every 6 hours • Use carbohydrate-free medications • Parents begin educational program
Day 2 (Tuesday) • Dinner, given as “eggnog,” providing 1/3 of calculated maintenance dinner calorie allowance • Blood glucose checks discontinued after dinner • Parents begin to check urine ketones periodically • Education continues
Day 3 (Wednesday) • Breakfast and lunch given as eggnog, providing 1/3 of maintenance breakfast and lunch calorie allowance • Dinner (still eggnog), increased to 2/3 of maintenance dinner calorie allowance • Education continues ·
Day 4 (Thursday) • Breakfast and lunch given as 2/3 of maintenance meal allowance • Dinner is first full ketogenic meal (not eggnog) • Education completed
Day 5 (Friday) • Full ketogenic diet breakfast (calories) given • Prescriptions reviewed and follow-up arranged • Child discharged to home
Modified Atkins Diet Protocol (22) • Copy of a carbohydrate counting guide provided to the family • Carbohydrates described in detail and restricted to 10 grams per day for the first month • Fats (e.g., 36% heavy whipping cream, oils, butter, mayonnaise) encouraged • Clear, carbohydrate-free, fluids and calories not restricted • Low-carbohydrate multivitamin (Unicap M™) and calcium (Calcimix™) supplementation prescribed • Urine ketones checked semiweekly and weight weekly • Medications unchanged for at least the first month, but changed if necessary to tablet or sprinkle (non liquid) preparations • Low-carbohydrate, store-bought products (e.g., shakes, candy bars, baking mixes) discouraged for at least the first month • Complete blood count, complete metabolic profile (SMA-20), fasting lipid profile, urine calcium, and urine creatinine obtained at baseline, 3, and 6 months
Alzheimers and ketotic diet references
β-hydroxybutyrate much more than a metabolite.
Essential roles of four-carbon backbone chemicals in the control of metabolism
Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41).
Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.
Abstract: Concentrations of acetyl–coenzyme A and nicotinamide adenine dinucleotide (NAD+) affect histone acetylation and thereby couple cellular metabolic status and transcriptional regulation. We report that the ketone body d-β-hydroxybutyrate (βOHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Administration of exogenous βOHB, or fasting or calorie restriction, two conditions associated with increased βOHB abundance, all increased global histone acetylation in mouse tissues. Inhibition of HDAC by βOHB was correlated with global changes in transcription, including that of the genes encoding oxidative stress resistance factors FOXO3A and MT2. Treatment of cells with βOHB increased histone acetylation at the Foxo3a and Mt2 promoters, and both genes were activated by selective depletion of HDAC1 and HDAC2. Consistent with increased FOXO3A and MT2 activity, treatment of mice with βOHB conferred substantial protection against oxidative stress.
Per the article: Cellular metabolites such as acetyl–coenzyme A (acetyl-CoA) and nicotinamide adenine dinucleotide (NAD+ ) influence gene expression by serving as cofactors for epigenetic modifiers that mediate posttranslational modification of histones . The activity of histone acetyltransferases (HATs) is dependent on nuclear acetyl-CoA concentrations and the deacetylase activity of class III HDACs, also called sirtuins, is dependent on NAD+ concentrations (4). Class I (HDAC1, 2, 3, 8), class II (HDAC4, 5, 6, 7, 9, 10), and class IV (HDAC11) HDACs are zincdependent enzymes, but endogenous regulators are not known. Small-molecule inhibitors of class I and class II HDACs include butyrate, a product of bacterial anaerobic fermentation (5). Butyrate is closely related to b-hydroxybutyrate (bOHB) (Fig. 1A), the major source of energy for mammals during prolonged exercise or starvation (6). Accumulation of bOHB in blood increases to 1 to 2 mM during fasting when the liver switches to fatty acid oxidation (7, 8), and to even higher concentrations during prolonged fasting (6 to 8 mM) – To determine whether bOHB might have HDAC inhibitor activity was the goal in the article.Our observation that bOHB is an endogenous HDAC inhibitor present in organisms at millimolar concentrations during prolonged fasting and CR reveals an example of integration between metabolic status and epigenetic changes. We show that changes in histone acetylation and gene expression caused by bOHB promote stress resistance in the kidney.For example, low-carbohydrate diets that induce substantial ketogenesis are broadly neuroprotective and enhance resistance of neurons to oxidative damage Ketone bodies are protective against oxidative stress in neocortical neurons. In addition, reduction in HDAC activity by either genetic manipulation or chemical inhibition extends life span in Drosophila Longevity Regulation by Drosophila Rpd3 Deacetylase and Caloric Restriction and Life extension in Drosophila by feeding a drug Inhibition of HDACs by bOHB might contribute to the beneficial effect of ketogenic diets and may be one mechanism by which calorie restriction confers health benefits. Finding Ponce de Leon’s Pill Challenges in Screening for Anti-Aging Molecules and Interventions to Slow Aging in Humans Are We Ready and Caloric restriction and its mimetics.
Insulin, ketone bodies and mitcohondrial energy transduction
Thematic Review Series_ Calorie Restriction and Ketogenic Diets_ Ketone ester effects on metabolism and transcription
Thematic Review Series_ Calorie Restriction and Ketogenic Diets_ Ketone Strong_ Emerging evidence for a therapeutic role of ketone bodies in neurological and neurodegenerative diseases b
Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss = meta-analysis
Abstract: The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional lowfat diet (LFD; i.e. a restricted-energy diet with less than 30 % of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect, Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was body weight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure, glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis, five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95 % CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95 % CI 20·27, 20·08) mmol/l, 1258 patients) and diastolic blood pressure (weighted mean difference 21·43 (95 % CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C (weighted mean difference 0·09 (95 % CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95 % CI 0·04, 0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the long term; hence, a VLCKD may be an alternative tool against obesity.
Other areas of interest in ketotic diets:
Treatment of Parkinson disease with diet-induced hyperketonemia A feasibility study
Abstract: Patients with idiopathic Parkinson disease (PD) may suffer from impairment of complex I activity involving—but not limited to—dopaminergic neurons of the substantia nigra pars compacta (SNpc).1 The resulting mitochondrial dysfunction could help explain some of the clinical manifestations of the illness. A recent study of isolated mouse brain mitochondria exposed to the complex I inhibitor, 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP), found that mitochondrial oxygen consumption and adenosine triphosphate (ATP) production were significantly increased when D--hydroxybutyrate (DHB) was added to the preparation, apparently by a complex II-dependent mechanism.2 These findings in mice suggested that dietinduced elevation of blood ketones (DHB and acetoacetate [AcAc]) to concentrations sufficient to replace a substantial proportion of glucose as the brain’s fuel might bring about symptomatic improvement in patients with PD by bypassing the presumed complex I defect and boosting mitochondrial function and ATP production. In addition, in vitro and in vivo evidence that DHB protects against MPTP-induced neurotoxicity2,3 suggests that sufficiently prolonged nutritional hyperketonemia might also help delay the progression of idiopathic PD. To increase blood ketones to concentrations within the “therapeutic” range (2 to 7 mmol/L), patients are usually maintained on a “4:1 hyperketogenic diet” (HKD), consisting (by weight) of 4 parts fat and 1 part of a carbohydrate-protein mixture).4 Although this kind of diet has been used successfully for decades for treatment of children and adults with medication-resistant seizure disorders,5 it is difficult to follow; moreover, after prolonged use, significant elevations may occur in serum low-density lipoprotein (LDL) cholesterol and other potentially atherogenic serum lipids.6 Given evidence that ketones crossing the bloodbrain barrier may bypass or compensate for the defect in complex I activity implicated in PD, it seemed desirable to test whether a HKD can benefit patients with PD. However, before attempting an extensive outpatient study, we deemed it essential to determine in a small series whether: 1) ambulatory patients with PD would be able to prepare a HKD in their own homes and remain on it for at least 4 weeks; 2) substitution of mono- and polyunsaturated fats for saturated fats, wherever possible, would mitigate the increases in the serum total cholesterol concentration expected from a very high fat diet; 3) evidence could be obtained to support the clinical safety of the HKD approach in the patients with PD. At best, the improved scores support the safety of the HKD approach. A placebo effect on UPDRS scores has been documented in numerous pharmacologic trials in PD10 and could have occurred in our patients. The studies of isolated mouse brain mitochondria exposed to MPTP, referred to earlier,2 found that ketone supplementation increases the generation of reactive oxygen species, thought by many to be a key mediator of nigral neuron degeneration. This observation is a cause for concern; however, the same investigation also showed DHB to be neuroprotective in the presence of MPTP. Moreover, despite extensive experience with HKDs for treatment of drugresistant epilepsy, there have been no reports of neurodegeneration attributable to diet-induced hyperketonemia sustained for many years. Ketone Bodies, Potential Therapeutic Uses – d-β-Hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease –
The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis.
A ketogenic diet has been shown to reduce the generation of reactive oxygen species through its effect on uncoupling proteins. It also increases levels of antioxidant agents including catalase and glutathione through its inhibitory action on histone deacetylases and activation of the Nrf2 pathway. 9.1. The Ketogenic Diet Increases Mitochondrial Uncoupling Protein Levels. The process of oxidative phosphorylation generates reactive oxygen species. The extent of reactive oxygen species generation correlates strongly with the potential difference across the inner mitochondrial membrane. Uncoupling proteins (UCPs) can reduce this potential difference by allowing the entry of protons into the mitochondrial matrix. Although this “mild” uncoupling may incur a small reduction in ATP generated through oxidative phosphorylation, its overall net effect is to enhance respiration and ATP levels through a reduction in reactive oxygen species formation and protection from apoptotic events . A ketogenic diet appears to promote UCP activity, specifically the activity of UCP2, UCP4, and UCP5 with a corresponding decline in reactive oxygen species . 9.2. Ketones Inhibit Histone Deacetylases. The ketone betahydroxybutyrate has a direct, dose-dependent inhibitory activity on class I histone deacetylases (HDACs) including HDAC1, HDAC3, and HDAC4. The ketone acetoacetate has also been shown to inhibit class I and class IIa HDACs. Beta-hydroxybutyrate’s inhibition of HDAC promotes the acetylation of histone H3 lysine 9 and histone H3 lysine 14 and increases the transcription of genes regulated by FOXO3A. These include genes leading to the expression of the antioxidant enzymes mitochondrial superoxide dismutase and catalase . 9.3. A Ketogenic Diet Leads to the Activation of the Nrf2 Pathway. The ketogenic diet raises glutathione levels in the hippocampus of rats . This is thought to occur through the Nrf2 (nuclear factor erythroid 2-related factor) pathway. When the ketogenic diet is first initiated, there is a temporary increase in oxidative stress.This may be activating Nrf2, since, a week after the temporary rise in oxidative stress, there is increased expression of Nrf2. Three weeks after the start of the diet, oxidative stress declines to below baseline levels and Nrf2 remains raised. the diet, oxidative stress declines to below baseline levels and Nrf2 remains raised . 10. The Effect of the Ketogenic Diet on ATP Levels A ketogenic diet enhances ATP production. The administration of beta-hydroxybutyrate immediately following bilateral common carotid artery ligation in a mouse model of global cerebral ischaemia preserves ATP levels . Feeding mice a ketogenic diet for three weeks resulted in increased levels of ATP and the ATP/ADP ratio in the brain . The improvement in ATP levels may partly be explained through the ability of the ketogenic diet to reduce oxidative stress. Although the diet may reduce reactive oxygen species generation through an increase in UCP activity, any reduction in oxidative phosphorylation incurred through UCP activity is outweighed by the enhancement of respiration and associated ATP production occurring as a result of reduced oxidative stress. A ketogenic diet also appears to preserve ATP levels in the event of mitochondrial respiratory chain dysfunction, possibly through the replenishment of TCA cycle intermediates . Beta-hydroxybutyrate attenuates the decrease in ATP production caused by a defect in complex I of the electron transport chain. It is thought to increase levels of the TCA intermediate succinate, which bypasses complex I when entering the TCA cycle [65, 72]. This carries considerable implications for MS, since defects in complex I within the electron transport chain have been observed in white matter lesions as well as in “normal” regions of the motor cortex [39, 73]. Ketones can also preserve ATP levels if complex II of the electron transport chain is inhibited, but this effect shows some regional specificity . 11. The Effect of the Ketogenic Diet on Mitochondrial Biogenesis Mitochondrial biogenesis within the rat hippocampus and cerebellar vermis is increased by the ketogenic diet [75, 76]. Although the precise pathway for this is not known, it is thought to involve the PGC1? family of transcriptional coactivators, which promote transcription factors including NRF-1, NRF-2, and ERR? . 12. The Effect of the Ketogenic Diet on Inflammation The anti-inflammatory effect of a ketogenic diet has been demonstrated in a murine model of lipopolysaccharideinduced fever . In a rat model of MS, the diet suppressed the expression of inflammatory cytokines and enhanced CA1 hippocampal synaptic plasticity and long-term potentiation, which resulted in improved learning, memory, and motor ability . The anti-inflammatory effect of a ketogenic diet may partly be explained through the inhibition of the NLRP3 inflammasome by beta-hydroxybutyrate in a manner that is independent of starvation-induced mechanisms such as AMPK, autophagy, or glycolytic inhibition. The NLRP3 inflammasome is responsible for the cleavage of procaspase-1 into caspase-1 and the activation of the cytokines IL-1? and IL-18. Its inhibition prevents IL-1? and IL-18 generation and their downstream effects . 13. The Neuroprotective Properties of the Ketogenic Diet Ketone bodies play a neuroprotective role in animal models of neurodegeneration [69, 81]. ATP-sensitive potassium channels (K ATP channels) located on the cell surface of neurons stabilize neuronal excitability. Ketones promote an “open state” of these channels and confer neuronal stability . K ATP channels also play a role in mitochondrial function and in cell death. The “open state” of K ATP channels located on the inner mitochondrial membrane prevents the formation of mitochondrial permeability transition pores (MPTPs) that can lead to mitochondrial swelling and cell death. Acetoacetate and beta-hydroxybutyrate have been shown to increase the threshold for calcium-induced MPTP formation . 14. The Regional Variation of the Effect of Ketones in the Mouse Cerebellum Despite these seemingly positive effects on mitochondrial bioenergetics, the effects of a ketogenic diet on mitochondria within the mouse brain are not homogenous and some results appear conflicting. Although the study on the murine model of EAE demonstrated improved CA1 synaptic plasticity, in another study, on rats, although a KD prevented age-related morphological changes within the outer layer of the dentate gyrus of the cerebellum, it produced negative changes within the CA1 region . In a study on rats fed a ketogenic diet for 8 weeks, antioxidant status was elevated within the hippocampus but not in the cerebral cortex and antioxidant activity was seen to be reduced within the cerebellum.Despite its high fat component, the ketogenic diet is safe and even beneficial for cardiometabolic risk factors . It has been in continuous use for almost a century for the treatment of epilepsy and has shown good tolerability, even in children . Current ketogenic diet protocols involve a range of options, which encourages patient compliance. Where compliance may pose a challenge, mimicry of various components of the ketogenic pathway through the use of ketone analogues may offer a palatable therapeutic option . Supplementation with ketones to induce ketosis has also shown an acceptable safety and tolerability profile .
Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects and The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells <<< safety of Ketogenic diet
Ketogenic Blog << Blog site
Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins.
Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (<50 g carbohydrate/d) for 6 weeks would improve lipid profiles and insulin sensitivity, reduce blood pressure, decrease cellular adhesion and inflammatory biomarkers, and augment VEF (flow-mediated dilation and forearm blood flow) in statin users. Participants (n = 21; 59.3 ± 9.3 y, 29.5 ± 3.0 kg/m2 ) decreased total caloric intake by approximately 415 kcal at 6 weeks (P < .001). Daily nutrient intakes at baseline (46/36/17% carb/fat/pro) and averaged across the intervention (11/58/28% carb/fat/pro) demonstrated dietary compliance, with carbohydrate intake at baseline nearly 5-fold greater than during the intervention (P < .001). Compared to baseline, both systolic and diastolic blood pressure decreased after 3 and 6 weeks (P < .01). Peak forearm blood flow, but not flow-mediated dilation, increased at week 6 compared to baseline and week 3 (P ≤ .03). Serum triglyceride, insulin, soluble E-Selectin and intracellular adhesion molecule-1 decreased (P < .01) from baseline at week 3, and this effect was maintained at week 6. In conclusion, these findings demonstrate that individuals undergoing statin therapy experience additional improvements in metabolic and vascular health from a 6 weeks CRD as evidenced by increased insulin sensitivity and resistance vessel endothelial function, and decreased blood pressure, triglycerides, and adhesion molecules.
Potential Therapeutic Use of the Ketogenic Diet in Autism Spectrum Disorders < consideration for use in Autism —> I also add this: Gastrointestinal dysfunction in autism spectrum disorder the role of the mitochondria and the enteric microbiome and this Enteric short-chain fatty acids microbial messengers of metabolism, mitochondria, and mind implications in autism spectrum disorders
Of interest re: SCFA : Cocobiota Implications for Human Health. << Current advances in molecular microbiology and analytical food chemistry suggest that processed cocoa beans and cocoa-based products may contain some substances and chemical compounds of microbial and fungal origin which are highly beneficial to human health. Taking into consideration the obvious significance of bacterial and fungal species in the process of fermentation of cocoa beans as well as their potential impact on human health, we introduce herein a new term COCOBIOTA. We define cocobiota as a specific unity of bacteria and fungi which drives spontaneous postharvest fermentation of cocoa beans and which may have some health effect through various primary and secondary metabolites of bacterial-fungal origin present in cocoa powder and dark chocolate
Moody microbes or fecal phrenology what do we know about the microbiota-gut-brain axis << Microbiome and SCFA related behaviors
Reversal of Diabetic Nephropathy by a Ketogenic Diet <<< Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions 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 determined.
The Effect of a Low-Carbohydrate, Ketogenic Diet on Nonalcoholic Fatty Liver Disease A Pilot Study << Abstract Nonalcoholic fatty liver disease is an increasingly common condition that may progress to hepatic cirrhosis. This pilot study evaluated the effects of a low-carbohydrate, ketogenic diet on obesity-associated fatty liver disease. Five patients with a mean body mass index of 36.4 kg/m2 and biopsy evidence of fatty liver disease were instructed to follow the diet (<20 g/d of carbohydrate) with nutritional supplementation for 6 months. Patients returned for group meetings biweekly for 3 months, then monthly for the second 3 months. The mean weight change was − 12.8 kg (range 0 to − 25.9 kg). Four of 5 posttreatment liver biopsies showed histologic improvements in steatosis (P = .02) inflammatory grade (P = .02), and fibrosis (P = .07). Six months of a lowcarbohydrate, ketogenic diet led to significant weight loss and histologic improvement of fatty liver disease. Further research is into this approach is warranted.
Also: Middle and Long-Term Impact of a Very Low-Carbohydrate Ketogenic Diet on Cardiometabolic Factors A Multi-Center, Cross-Sectional, Clinical Study. Results All the predetermined goals—namely safety, reduction of body weight and CV risk factors levels—have been reached with a significant reduction of body weight (from baseline to 4 weeks (-7 ± 5 kg, p\0.001), from 4 to 12 weeks (-5 ± 3 kg, p\0.001), no changes from 12 weeks to 12 months; waistline (from baseline to 4 weeks (-7 ± 4 cm, p\0.001), from 4 to 12 weeks (-5 ± 7 cm, p\0.001), no changes from 12 weeks to 12 months; fatty mass (from baseline to 4 weeks (-3.8 ± 3.8 %, p\0.001), from 4 to 12 weeks (-3.4 ± 3.5 %, p\0.001), no changes from 12 weeks to 12 months; SBP from baseline to 3 months (-10.5 ± 6.4 mmHg, p\0.001), no further changes after 1 year of observation). Conclusion the tested VLCD diet suggested by trained general physicians in the setting of clinical practice seems to be able to significantly improve on the middle-term a number of anthropometric, haemodynamic and laboratory with an overall good tolerability.
Middle and Long-Term Impact of a Very Low-Carbohydrate Ketogenic Diet on Cardiometabolic Factors A Multi-Center, Cross-Sectional, Clinical Study. CONCLUSION: the tested VLCD diet suggested by trained general physicians in the setting of clinical practice seems to be able to significantly improve on the middle-term a number of anthropometric, haemodynamic and laboratory with an overall good tolerability.
Beyond weight loss- a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. <<< Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician’s hand.
Ketosis, ketogenic diet and food intake control a complex relationship l Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.
Effect of Ketogenic Mediterranean diet with phytoextracts and low CHO-high protein meals << The KEMEPHY diet lead to weight reduction, improvements in cardiovascular risk markers, reduction in waist circumference and showed good compliance.
Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson’s disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review.
High-Fat and Ketogenic Diets in Amyotrophic Lateral Sclerosis << In summary, there are strong epidemiologic data showing that malnutrition is a common symptom of amyotrophic lateral sclerosis both in humans and in mice and may contribute to disease progression. There is also epidemiologic evidence that increased dietary fat and cholesterol intake might reduce the risk of amyotrophic lateral sclerosis and the rate disease progression. Finally, data from animal studies strongly suggest that increasing dietary intake of fat ameliorates disease progression. However, determining whether amyotrophic lateral sclerosis patients should be treated with a high-fat or ketogenic diet can be based only on randomized double-blind placebo-controlled interventional trials.
Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis a randomised, double-blind, placebo-controlled phase 2 trial.
A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome < use of ketogenic diet in GLUT transporter problems
Beta hydroxybutyrate upregulates genes to prevent oxidative stress as reviewed in the above articles.
8-Volek-Moving Toward a Personalized Approach to Nutrition << excellent slide show
Metabolic therapeutics and ketogenic diet 2016 << presentation
Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet A hypocaloric carbohydrate restricted diet (CRD) had two striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite higher intake than a low fat diet, and (2) a decrease in inflammation despite a significant increase in arachidonic acid (ARA).These findings are consistent with the concept that dietary saturated fat is efficiently metabolized in the presence of low carbohydrate, and that a CRD results in better preservation of plasma ARA.
A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. n Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet.
A Low-Carbohydrate, Whole-Foods Approach to Managing Diabetes and Prediabetes
A Low-Carbohydrate, Whole-Foods Approach to Managing Diabetes and Prediabetes We recently proposed that the biological markers improved by carbohydrate restriction were precisely those that define the metabolic syndrome (MetS), and that the common thread was regulation of insulin as a control element. We specifically tested the idea with a 12-week study comparing two hypocaloric diets (approximately 1,500 kcal): a carbohydrate-restricted diet (CRD) (%carbohydrate:fat:protein = 12:59:28) and a low-fat diet (LFD) (56:24:20) in 40 subjects with atherogenic dyslipidemia. Both interventions led to improvements in several metabolic markers, but subjects following the CRD had consistently reduced glucose (-12%) and insulin (-50%) concentrations, insulin sensitivity (-55%), weight loss (-10%), decreased adiposity (-14%), and more favorable triacylglycerol (TAG) (-51%), HDL-C (13%) and total cholesterol/HDL-C ratio (-14%) responses. In addition to these markers for MetS, the CRD subjects showed more favorable responses to alternative indicators of cardiovascular risk: postprandial lipemia (-47%), the Apo B/Apo A-1 ratio (-16%), and LDL particle distribution. Despite a threefold higher intake of dietary saturated fat during the CRD, saturated fatty acids in TAG and cholesteryl ester were significantly decreased, as was palmitoleic acid (16:1n-7), an endogenous marker of lipogenesis, compared to subjects consuming the LFD. Serum retinol binding protein 4 has been linked to insulin-resistant states, and only the CRD decreased this marker (-20%). The findings provide support for unifying the disparate markers of MetS and for the proposed intimate connection with dietary carbohydrate. The results support the use of dietary carbohydrate restriction as an effective approach to improve features of MetS and cardiovascular risk.
Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. :Exogenous ketone supplementation caused a rapid and sustained elevation of βHB, reduction of glucose, and little change to lipid biomarkers compared to control animals.
Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation
Abstract: Abnormal distribution of plasma fatty acids and increased inflammation are prominent features of metabolic syndrome. We tested whether these components of metabolic syndrome, like dyslipidemia and glycemia, are responsive to carbohydrate restriction. Overweight men and women with atherogenic dyslipidemia consumed ad libitum diets very low in carbohydrate (VLCKD) (1504 kcal:%CHO:fat:protein = 12:59:28) or low in fat (LFD) (1478 kcal:%CHO:fat:protein = 56:24:20) for 12 weeks. In comparison to the LFD, the VLCKD resulted in an increased proportion of serum total n-6 PUFA, mainly attributed to a marked increase in arachidonate (20:4n-6), while its biosynthetic metabolic intermediates were decreased. The n-6/n-3 and arachidonic/eicosapentaenoic acid ratio also increased sharply. Total saturated fatty acids and 16:1n-7 were consistently decreased following the VLCKD. Both diets significantly decreased the concentration of several serum inflammatory markers, but there was an overall greater anti-inflammatory effect associated with the VLCKD, as evidenced by greater decreases in TNF-alpha, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1. Increased 20:4n-6 and the ratios of 20:4n-6/20:5n-3 and n-6/n-3 are commonly viewed as pro-inflammatory, but unexpectedly were consistently inversely associated with responses in inflammatory proteins. In summary, a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet.
The above shows that despite being higher in saturated fat, a ketogenic diet decreases circulating levels of saturated fatty acids
Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum
Ketogenic diets and pain.
Drivers of age-related inflammation and strategies for healthspan extension
Ageing Is Associated with Decreases in Appetite and Energy Intake–A Meta-Analysis in Healthy Adults.
Effects of food form on food intake and postprandial appetite sensations, glucose and endocrine responses, and energy expenditure in resistance trained v. sedentary older adults.
Leucine Supplementation and Intensive Training
The Neuropharmacology of the Ketogenic Diet
Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet
Alternat fuel utilization by brain
Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases.
Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases.
Neuro-immune Dysfunction During Brain Agin New Insights in Microglial Cell Regulation
Nutrition and muscle protein synthesis a descriptive review
Endurance Exercise Training Up-Regulates Lipolytic proteins and reduces tg content in skeletal muscle of obese subjects
Acute nutritional ketosis implications for exercise performance and metabolism <<< Exercise related ketosis
Beneficial effects of ketogenic diet in obese diabetic subjects. < Excellent study showing sustained weight loss over a year period – also blood lipids improvement were sustained as well using a well-crafted ketogenic diet. Diet guidelines included meat, fish, poultry, full fat cheeses, green vegetables, 5 T/day olive oil, flax seed oil.
Excess carbohydrates taken in above which you can metabolize will be converted to fat. This results in increased circulating levels of saturated fats, especially palimitoleic acid (16:1) and exacerbates insulin resistance.
If you have insulin resistance – restricting sugars and starches can profoundly benefit all risk factors. Insulin resistance is a carbohydrate intolerant state.
Higher levels of palmitoleic acid in the blood stream or adipose tissue are associated with bad outcomes such as: obesity, hypertriglyceridemia, hyperglycemia, inflammation, metabolic syndrome, heart failure, increased incidence of prostate cancer, coronary artery disease, diabetes, etc
Even without high blood sugar, increase pamitoleic acid in the blood is associated with increased risk of developing type 2 diabetes.
Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9¡9.9 yr, BMI 37.9¡6.3 kg/m2 ) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes.
Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans Background: Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease (NAFLD). Objective: We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this is reversible by weight loss. Design: Sixteen subjects [BMI (kg/m2 ): 30.6 6 1.2] were placed on a hypercaloric diet (.1000 kcal simple carbohydrates/d) for 3 wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped for rs739409 in the PNPLA3 gene. Before and after overfeeding and after hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate (18:2n26) in serum and VLDL triglycerides was used as an index of DNL. Results: Carbohydrate overfeeding increased weight (6SEM) by 2% (1.8 6 0.3 kg; P , 0.0001) and liver fat by 27% from 9.2 6 1.9% to 11.7 6 1.9% (P = 0.005). DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3-148II but not PNPLA3-148MM. During the hypocaloric diet, the subjects lost 4% of their weight (3.2 6 0.6 kg; P , 0.0001) and 25% of their liver fat content (from 11.7 6 1.9% to 8.8 6 1.8%; P , 0.05). Conclusions: Carbohydrate overfeeding for 3 wk induced a .10-fold greater relative change in liver fat (27%) than in body weight (2%). The increase in liver fat was proportional to that in DNL. Weight loss restores liver fat to normal. These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD
Effects of short-term carbohydrate or fat overfeeding on energy expenditure and plasma leptin concentrations in healthy female subjects
Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation. Abnormal distribution of plasma fatty acids and increased inflammation are prominent features of metabolic syndrome. We tested whether these components of metabolic syndrome, like dyslipidemia and glycemia, are responsive to carbohydrate restriction. Overweight men and women with atherogenic dyslipidemia consumed ad libitum diets very low in carbohydrate (VLCKD) (1504 kcal:%CHO:fat:protein = 12:59:28) or low in fat (LFD) (1478 kcal:%CHO:fat:protein = 56:24:20) for 12 weeks. In comparison to the LFD, the VLCKD resulted in an increased proportion of serum total n-6 PUFA, mainly attributed to a marked increase in arachidonate (20:4n-6), while its biosynthetic metabolic intermediates were decreased. The n-6/n-3 and arachidonic/eicosapentaenoic acid ratio also increased sharply. Total saturated fatty acids and 16:1n-7 were consistently decreased following the VLCKD. Both diets significantly decreased the concentration of several serum inflammatory markers, but there was an overall greater anti-inflammatory effect associated with the VLCKD, as evidenced by greater decreases in TNF-alpha, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1. Increased 20:4n-6 and the ratios of 20:4n-6/20:5n-3 and n-6/n-3 are commonly viewed as pro-inflammatory, but unexpectedly were consistently inversely associated with responses in inflammatory proteins. In summary, a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet.
Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations. results: We identified 45 different TGs in serum. Serum TGs containing saturated and monounsaturated fatty acids were positively, while TGs containing essential linoleic acid (18:2 n-6) were negatively correlated with HOMA-IR. Specific serum TGs that correlated positively with HOMA-IR were also significantly positively related to HOMA-IR when measured in very-low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs) and LDL, but not in HDL subfraction 2 (HDL(2)) or 3 (HDL(3)). Analyses of proportions of esterified fatty acids within lipoproteins revealed that palmitic acid (16:0) was positively related to HOMA-IR when measured in VLDL, IDL and LDL, but not in HDL(2) or HDL(3). Monounsaturated palmitoleic (16:1 n-7) and oleic (18:1 n-9) acids were positively related to HOMA-IR when measured in HDL(2) and HDL(3), but not in VLDL, IDL or LDL. Linoleic acid was negatively related to HOMA-IR in all lipoproteins Conclusions: Serum concentrations of specific TGs, such as TG(16:0/16:0/18:1) or TG(16:0/18:1/18:0), may be more precise markers of insulin resistance than total serum TG concentrations.
PLASMA SATURATED FAT Predicts heart Disease
Fatty-acid composition of serum lipids predicts myocardial infarction. Healthy men with higher plasma SFA (16:0 and 18:0) had significantly greater incidience of heart attack.
During a follow-up of five to seven years 33 out of 1222 middle-aged men initially free of coronary heart disease sustained fatal or non-fatal myocardial infarction or died suddenly. The fatty-acid composition of serum triglycerides, phospholipids, and cholesterol esters had been measured at the start of the surveillance in these men and in a control group of 64 men matched for age, serum cholesterol and triglyceride concentrations, blood pressure, obesity, smoking, and one-hour glucose tolerance. Palmitic and stearic acids of phospholipids were significantly higher and linoleic and most polyunsaturated fatty acids, including arachidonic acid and eicosapentaenoic acid, of phospholipids were lower in the subjects who sustained coronary events compared with the controls. Linoleic acid tended to correlate negatively with blood pressure while other polyunsaturated fatty acids, especially eicosapentaenoic acid, exhibited a negative correlation with blood pressure and relative body weight in the controls but not in the subjects who sustained coronary events. These findings suggest that the fatty-acid pattern of serum phospholipids is an independent risk factor for coronary heart disease.
Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes systematic review and meta-analysis of observational studies.
For saturated fat, three to 12 prospective cohort studies for each association were pooled (five to 17 comparisons with 90,501-339,090 participants). Saturated fat intake was not associated with all cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97, 0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to 1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10). For trans fats, one to six prospective cohort studies for each association were pooled (two to seven comparisons with 12,942-230,135 participants). Total trans fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD mortality (1.28, 1.09 to 1.50), and total CHD (1.21, 1.10 to 1.33) but not ischemic stroke (1.07, 0.88 to 1.28) or type 2 diabetes (1.10, 0.95 to 1.27). Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18 (1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05 to 1.92) v 0.93 (0.73 to 1.18)). Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes (0.58, 0.46 to 0.74). The certainty of associations between saturated fat and all outcomes was “very low.” The certainty of associations of trans fat with CHD outcomes was “moderate” and “very low” to “low” for other associations.
Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats. Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats.
Serum fatty acids and the risk of coronary heart disease – [Men who had heart attacks had higher serum palmitic acid (16:0) and a 68% greater risk of heart disease] To examine the relation between serum fatty acids and coronary heart disease (CHD), the authors conducted a nested case-control study of 94 men with incident CHD and 94 men without incident CHD who were enrolled in the Usual Care group of the Multiple Risk Factor Intervention Trial between December 1973 and February 1976. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and examined their association with CHD. In all multivariate models, levels of the cholesterol ester saturated fatty acid palmitic acid (16:0) were directly associated with CHD risk (standardized odds ratio = 1.68; 95% confidence interval 1.10-2.55 in the model that adjusted for total plasma cholesterol level). Levels of the phospholipid omega-3 fatty acid docosapentaenoic acid (22:5) were inversely associated with CHD risk in the two multivariate models that controlled for the effects of total plasma cholesterol level or high density lipoprotein cholesterol to total plasma cholesterol ratio (standardized odds ratio = 0.58; 95% confidence interval 0.38-0.89 in the first model that controlled for total plasma cholesterol level). In contrast to the first two multivariate models, levels of the docosahexaenoic acid (22:6) were inversely associated with CHD risk in a third multivariate model that controlled for the effects of high density lipoprotein cholesterol to low density lipoprotein cholesterol ratio (standardized odds ratio = 0.57; 95% confidence interval 0.36-0.90). These findings are consistent with other evidence indicating that saturated fatty acids are directly correlated with CHD and that omega-3 polyunsaturated fatty acids are inversely correlated with CHD. Because these associations were present after adjustment for blood lipid levels, other mechanisms, such as a direct effect on blood clotting, may be involved.
Plasma fatty acid composition and incidence of coronary heart disease in middle aged adults_ the Atherosclerosis Risk in Communities (ARIC) Study In 282 out of 3591 men who had heart attacks over 11 years, plasma CE and PL SFA’s were higher
To prospectively investigate the relation of plasma cholesterol ester (CE) and phospholipid (PL) fatty acid (FA) composition with incidence of coronary heart disease (CHD).
METHODS AND RESULTS:
3,591 white participants in the Minneapolis field center of the Atherosclerosis Risk in Communities Study, aged 45-64 years, were studied. Plasma FA composition of CEs and PLs was quantified using gas-liquid chromatography and expressed as percentage of total FAs. Incident CHD was identified during 10.7 years of follow-up. In both CE and PL fractions, the proportions of stearic (18:0) acid, dihomo-gamma-linolenic (20:3n6) acid and total saturated fatty acids (SFAs) were significantly higher while arachidonic (20:4n6) acid and total polyunsaturated fatty acids (PUFAs) were significantly lower among participants who developed incident CHD (n = 282). After adjusting for age, gender, smoking, alcohol drinking, sports activity, and non-FA dietary factors, the incidence of CHD was significantly and positively associated with the proportion of dihomo-gamma-linolenic acid but inversely associated with arachiadonic acid. The multiply-adjusted rate ratios (RRs) of CHD incidence for the highest versus the lowest quintile were 1.31 in CE and 1.44 in PL for dihomo-gamma-linolenic acid (p for trend: 0.05 and 0.017, respectively), 0.59 in CE and 0.65 in PL for arachidonic acid (p: 0.016 and 0.024, respectively). Also significantly and positively associated with incident CHD were PL stearic acid and CE linolenic (18:3n3) acid. Only a borderline significant positive association was observed for total SFAs in CE (multivariate RRs across quintiles: 1.00, 1.15, 1.40, 1.62, 1.32; p = 0.07). Total PUFAs or monounsaturated FA were not independently associated with CHD.
Our study found a weak positive association of SFAs with incident CHD. Our findings also confirm that FA metabolism in the body, such as the activity of delta-5 desaturase, which converts dihomo-gamma-linolenic acid to arachidonic acid, may affect the development of CHD.
Plasma fatty acid composition and incident heart failure in middle-aged adults the Atherosclerosis Risk in Communities (ARIC) Study IN this study 197 out of 3592 adults who developed heart failure, plasma CE (cholesterol esthers) and PL(phospholipids_ SFAs were higher
DIETARY SATURATED FAT AND HEART DISEASE -3 RECENT METANALYSIS:
Dietary Fat and Coronary Heart Disease summary of evidence from prospective cohort and randomised controlled trials – No association bewteen SFA intake and CHD deaths or events (280,000 people in 28 studies over 4-25 years)
Major types of dietary fat and risk of coronary heart disease a pooled analysis of 11 cohort studies. Increased SFA intake not associated with CHD events when replaced with CHO or MUFA (344,698 people from 11 studies over 4-10 years)
Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. – No association between SFA intake and CVD, CHD, or stroke (347,747 people from 21 pooled studies 5-23 years)
Dietary Fatty Acids and Risk of Coronary Heart Disease in Men Our results suggest that SFA intake is not an independent risk factor for CHD, even in a population with higher ranges of SFA intake. In contrast, polyunsaturated fat intake was associated with lower risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. Further investigation on the effect of monounsaturated fat on the CHD risk is warranted.
Dairy consumption and risk of cardiovascular disease an updated meta-analysis of prospective cohort studies. A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.
23 Studies on Low-Carb and Low-Fat Diets – Time to Retire The Fad << EXCELLENT LINKS to STUDIES
Low-Carb Diets – Healthy, but Hard to Stick to_
Randomized Controlled Trials in Nutrition
12 Popular Weight Loss Pills and Supplements Reviewed
Sodium Bicarbonate Supplements and Exercise Performance
Low-Carb_Ketogenic Diets and Exercise Performance
Ketogenic Diets and Cancer – A Review of The Research
A Ketogenic Diet to Lose Weight and Fight Disease
The Ketogenic Diet 101_ A Detailed Beginner’s Guide
The Alkaline Diet Myth_ An Evidence-Based Review
Low-Carb vs Vegan and Vegetarian Diets
5 Studies on The Paleo Diet – Does it Actually Work_
10 Graphs That Show the Power of a Ketogenic Diet
10 False Things People Say About Low-Carb Diets
12 Popular Weight Loss Pills and Supplements Reviewed
Randomized Controlled Trials in Nutrition
The Atkins Diet_ Everything You Need to Know (Literally)
7 Healthy Low-Carb Meals in Under 10 Minutes
4 Meal Plans For Diets That Are Supported by Science
What is Ketosis, and is it Healthy_