Abstract Background Many successful ultra-endurance athletes have switched from a high-carbohydrate to a low-carbohydrate diet, but they have not previously been studied to determine the extent of ...metabolic adaptations. Methods Twenty elite ultra-marathoners and ironman distance triathletes performed a maximal graded exercise test and a 180 min submaximal run at 64% VO2 max on a treadmill to determine metabolic responses. One group habitually consumed a traditional high-carbohydrate (HC: n = 10 , %carbohydrate:protein:fat = 59:14:25) diet, and the other a low-carbohydrate (LC; n = 10 , 10:19:70) diet for an average of 20 months (range 9 to 36 months). Results Peak fat oxidation was 2.3-fold higher in the LC group (1.54 ± 0.18 vs 0.67 ± 0.14 g/min; P = 0.000 ) and it occurred at a higher percentage of VO2 max (70.3 ± 6.3 vs 54.9 ± 7.8%; P = 0.000 ). Mean fat oxidation during submaximal exercise was 59% higher in the LC group (1.21 ± 0.02 vs 0.76 ± 0.11 g/min; P = 0.000 ) corresponding to a greater relative contribution of fat (88 ± 2 vs 56 ± 8%; P = 0.000 ). Despite these marked differences in fuel use between LC and HC athletes, there were no significant differences in resting muscle glycogen and the level of depletion after 180 min of running (− 64% from pre-exercise) and 120 min of recovery (− 36% from pre-exercise). Conclusion Compared to highly trained ultra-endurance athletes consuming an HC diet, long-term keto-adaptation results in extraordinarily high rates of fat oxidation, whereas muscle glycogen utilization and repletion patterns during and after a 3 hour run are similar.
Rethinking fat as a fuel for endurance exercise Volek, Jeff S.; Noakes, Timothy; Phinney, Stephen D.
European journal of sport science,
February 2015, Letnik:
15, Številka:
1
Journal Article
Recenzirano
A key element contributing to deteriorating exercise capacity during physically demanding sport appears to be reduced carbohydrate availability coupled with an inability to effectively utilize ...alternative lipid fuel sources. Paradoxically, cognitive and physical decline associated with glycogen depletion occurs in the presence of an over-abundance of fuel stored as body fat that the athlete is apparently unable to access effectively. Current fuelling tactics that emphasize high-carbohydrate intakes before and during exercise inhibit fat utilization. The most efficient approach to accelerate the body's ability to oxidize fat is to lower dietary carbohydrate intake to a level that results in nutritional ketosis (i.e., circulating ketone levels >0.5 mmol/L) while increasing fat intake for a period of several weeks. The coordinated set of metabolic adaptations that ensures proper interorgan fuel supply in the face of low-carbohydrate availability is referred to as keto-adaptation. Beyond simply providing a stable source of fuel for the brain, the major circulating ketone body, beta-hydroxybutyrate, has recently been shown to act as a signalling molecule capable of altering gene expression, eliciting complementary effects of keto-adaptation that could extend human physical and mental performance beyond current expectation. In this paper, we review these new findings and propose that the shift to fatty acids and ketones as primary fuels when dietary carbohydrate is restricted could be of benefit for some athletes.
Studies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We previously reported the effectiveness of a novel digitally-monitored continuous care intervention ...(CCI) including nutritional ketosis in improving weight, glycemic outcomes, lipid, and liver marker changes at 1 year. Here, we assess the effects of the CCI at 2 years.
An open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively. Primary outcomes were retention, glycemic control, and weight changes at 2 years. Secondary outcomes included changes in body composition, liver, cardiovascular, kidney, thyroid and inflammatory markers, diabetes medication use and disease status.
Reductions from baseline to 2 years in the CCI group resulting from intent-to-treat analyses included: HbA1c, fasting glucose, fasting insulin, weight, systolic blood pressure, diastolic blood pressure, triglycerides, and liver alanine transaminase, and HDL-C increased. Spine bone mineral density in the CCI group was unchanged. Use of any glycemic control medication (excluding metformin) among CCI participants declined (from 55.7 to 26.8%) including insulin (-62%) and sulfonylureas (-100%). The UC group had no changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had
< 0.00012.
The CCI group sustained long-term beneficial effects on multiple clinical markers of diabetes and cardiometabolic health at 2 years while utilizing less medication. The intervention was also effective in the resolution of diabetes and visceral obesity with no adverse effect on bone health.
Clinicaltrials.gov NCT02519309.
We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized ...participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly ...improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort.
We investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons.
The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m
). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (- 4.9%, P = 0.02), small LDL-P (- 20.8%, P = 1.2 × 10
), LDL-P size (+ 1.1%, P = 6.0 × 10
), ApoB (- 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10
), ApoB/ApoA1 ratio (- 9.5%, P = 1.9 × 10
), triglyceride/HDL-C ratio (- 29.1%, P < 10
), large VLDL-P (- 38.9%, P = 4.2 × 10
), and LDL-C (+ 9.9%, P = 4.9 × 10
). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10
) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased - 11.9% (P = 4.9 × 10
). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 × 10
). The UC group of 87 participants baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m
showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. The CCI group showed a greater rise in LDL-C.
A continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after 1 year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased. Trial registration Clinicaltrials.gov: NCT02519309. Registered 10 August 2015.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Carbohydrate restriction markedly improves glycemic control in patients with type 2 diabetes (T2D) but necessitates prompt medication changes. Therefore, we assessed the effectiveness ...and safety of a novel care model providing continuous remote care with medication management based on biometric feedback combined with the metabolic approach of nutritional ketosis for T2D management.
Methods
We conducted an open-label, non-randomized, controlled, before-and-after 1-year study of this continuous care intervention (CCI) and usual care (UC). Primary outcomes were glycosylated hemoglobin (HbA
1c
), weight, and medication use. Secondary outcomes included fasting serum glucose and insulin, HOMA-IR, blood lipids and lipoproteins, liver and kidney function markers, and high-sensitivity C-reactive protein (hsCRP).
Results
349 adults with T2D enrolled: CCI:
n
= 262 mean (SD); 54 (8) years, 116.5 (25.9) kg, 40.4 (8.8) kg m
2
, 92% obese, 88% prescribed T2D medication; UC:
n
= 87 (52 (10) years, 105.6 (22.15) kg, 36.72 (7.26) kg m
2
, 82% obese, 87% prescribed T2D medication. 218 participants (83%) remained enrolled in the CCI at 1 year. Intention-to-treat analysis of the CCI (mean ± SE) revealed HbA
1c
declined from 59.6 ± 1.0 to 45.2 ± 0.8 mmol mol
−1
(7.6 ± 0.09% to 6.3 ± 0.07%,
P
< 1.0 × 10
−16
), weight declined 13.8 ± 0.71 kg (
P
< 1.0 × 10
−16
), and T2D medication prescription other than metformin declined from 56.9 ± 3.1% to 29.7 ± 3.0% (
P
< 1.0 × 10
−16
). Insulin therapy was reduced or eliminated in 94% of users; sulfonylureas were entirely eliminated in the CCI. No adverse events were attributed to the CCI. Additional CCI 1-year effects were HOMA-IR − 55% (
P
= 3.2 × 10
−5
), hsCRP − 39% (
P
< 1.0 × 10
−16
), triglycerides − 24% (
P
< 1.0 × 10
−16
), HDL-cholesterol + 18% (
P
< 1.0 × 10
−16
), and LDL-cholesterol + 10% (
P
= 5.1 × 10
−5
); serum creatinine and liver enzymes (ALT, AST, and ALP) declined (
P
≤ 0.0001), and apolipoprotein B was unchanged (
P
= 0.37). UC participants had no significant changes in biomarkers or T2D medication prescription at 1 year.
Conclusions
These results demonstrate that a novel metabolic and continuous remote care model can support adults with T2D to safely improve HbA
1c
, weight, and other biomarkers while reducing diabetes medication use.
ClinicalTrials.gov Identifier
NCT02519309.
Funding
Virta Health Corp.
Plain Language Summary
Treatments for type 2 diabetes (T2D) have improved, yet T2D and being overweight are still significant public health concerns. Blood sugar in patients with T2D can improve quickly when patients eat significantly fewer dietary carbohydrates. However, this demands careful medicine management by doctors, and patients need support and frequent contact with health providers to sustain this way of living. The purpose of this study was to evaluate if a new care model with very low dietary carbohydrate intake and continuous supervision by a health coach and doctor could safely lower HbA1c, weight and need for medicines after 1 year in adults with T2D. 262 adults with T2D volunteered to participate in this continuous care intervention (CCI) along with 87 adults with T2D receiving usual care (UC) from their doctors and diabetes education program. After 1 year, patients in the CCI, on average, lowered HbA1c from 7.6 to 6.3%, lost 12% of their body weight, and reduced diabetes medicine use. 94% of patients who were prescribed insulin reduced or stopped their insulin use, and sulfonylureas were eliminated in all patients. Participants in the UC group had no changes to HbA1c, weight or diabetes medicine use over the year. These changes in CCI participants happened safely while dyslipidemia and markers of inflammation and liver function improved. This suggests the novel care model studied here using dietary carbohydrate restriction and continuous remote care can safely support adults with T2D to lower HbA1c, weight, and medicine use.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, ...CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT).
Analyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles.
At 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group.
Consumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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 (~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.
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