The human metabolic response to chronic ketosis without caloric restriction: Physical and biochemical adaptation

Phinney, Stephen D.; Bistrian, B R; Wolfe, R R; Blackburn, George L.

doi:10.1016/0026-0495(83)90105-1

Cited by 153 publications

(135 citation statements)

References 31 publications

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“…When non-tumour-bearing rats were fed on the MCT diet the increased concentration of ketone bodies in the blood was accompanied by a significant decrease (P<0.01) in the blood glucose concentration (Table II). This is consistent with the observation that ketosis induced in humans by a diet containing 85% of calories as fat is associated with a significant reduction in the blood glucose concentration (Phinney et al, 1983). Similarly, the induction of a systemic ketosis by the infusion of 3-hydroxybutyrate into man (Sherwin et al, 1975), dogs (Binkiewicz et al, 1974) or sheep (Radcliffe et al, 1983) has been shown to produce a significant decrease in the blood glucose concentration and is associated with a decrease in the rate of gluconeogenesis of both fed and fasted sheep (Radcliffe et al, 1983).…”

Section: Discussionsupporting

confidence: 88%

“…This phenomenon may allow for continued tumour growth in the wasted host, and may account for accelerated weight loss in tumourbearing individuals (Gold, 1971). Dietary induced systemic ketosis has been shown to reduce blood glucose concentration and glucose utilisation in man (Phinney et al, 1983). Moreover the supply of glycerol and alanine as precursors for gluconeogenesis is decreased in the ketotic state (see Robinson & Williamson, 1980).…”

mentioning

confidence: 99%

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Failure of systemic ketosis to control cachexia and the growth rate of the Walker 256 carcinosarcoma in rats

Fearon¹,

Tisdale²,

Preston³

et al. 1985

Br J Cancer

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Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

Failure of systemic ketosis to control cachexia and the growth rate of the Walker 256 carcinosarcoma in rats

Fearon¹,

Tisdale²,

Preston³

et al. 1985

Br J Cancer

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“…With the advent of the Ice Ages and the change to a low-carbohydrate diet, metabolic adaptations were necessary to accommodate this low glucose intake and to meet the specific requirement for glucose of the brain, foetus and mammary gland. Chronic ingestion of a low-carbohydrate, high-protein diet results in increased hepatic glucose production and decreased peripheral glucose utilisation, ie insulin resistance (Phinney et al, 1983;Rossetti et al, 1989). Periodic starvation, which was also a feature of the existence of our ancestors, results in the same metabolic profile as that occurring with a low-carbohydrate, highprotein diet, ie increased gluconeogenesis and peripheral insulin resistance (DeFronzo et al, 1978;Newman & Brodows, 1983).…”

Section: Historical Dietary Changes and The Development Of Insulin Rementioning

confidence: 99%

The ‘carnivore connection’—evolutionary aspects of insulin resistance

Colagiuri

Brand-Miller

2002

Eur J Clin Nutr

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Insulin resistance is common and is determined by physiological (aging, physical fitness), pathological (obesity) and genetic factors. The metabolic compensatory response to insulin resistance is hyperinsulinaemia, the primary purpose of which is to maintain normal glucose tolerance. The 'carnivore connection' postulates a critical role for the quantity of dietary protein and carbohydrate and the change in the glycaemic index of dietary carbohydrate in the evolution of insulin resistance and hyperinsulinaemia. Insulin resistance offered survival and reproductive advantages during the Ice Ages which dominated human evolution, during which a high-protein low-carbohydrate diet was consumed. Following the end of the last Ice Age and the advent of agriculture, dietary carbohydrate increased. Although this resulted in a sharp increase in the quantity of carbohydrate consumed, these traditional carbohydrate foods had a low glycaemic index and produced only modest increases in plasma insulin. The industrial revolution changed the quality of dietary carbohydrate. The milling of cereals made starch more digestible and postprandial glycaemic and insulin responses increased 2 -3 fold compared with coarsely ground flour or whole grains. This combination of insulin resistance and hyperinsulinaemia is a common feature of many modern day diseases. Over the last 50 y the explosion of convenience and takeaway 'fast foods' has exposed most populations to caloric intakes far in excess of daily energy requirements and the resulting obesity has been a major factor in increasing the prevalence of insulin resistance.

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“…It is assumed that the ketonemia induced by these diets is tolerated, based on those research studies that have measured ketone body production (Phinney et al, 1983;Langfort et al, 1996;Volek et al, 2002;Brehm et al, 2003Brehm et al, , 2005Meckling et al, 2004;Yancy et al, 2004;Boden et al, 2005). It is not known, however, if actual acidemia develops.…”

Section: Introductionmentioning

confidence: 99%

Acid-base analysis of individuals following two weight loss diets

Yancy

Olsen

Dudley³

et al. 2007

Eur J Clin Nutr

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Objective: To examine the effects of low-carbohydrate, ketogenic (LCKD) and low-fat (LFD) diets on acid-base status. Design: Prospective analysis of volunteers from two clinical trials. Participants: Subset of 39 volunteers from a randomized trial comparing the effects of an LCKD with an LFD, and a single-arm trial of an LCKD. Setting: Outpatient research clinic. Intervention: LCKD (initially o20 g of carbohydrate daily) or LFD (o30% of energy from fat, 500-1000 kcal energy reduction) instruction. Measurements: Arterial blood gas analysis, serum chemistries (electrolytes, urea nitrogen/creatinine, glucose, ketone bodies, lactate), anion gap, and urine ketone bodies measured at weeks 0, 2, 8, and 24. Results: Participants had a mean (7standard deviation) age of 43.579.3 years; 28 (72%) were female, 29 (74%) were Caucasian. Using linear mixed-model analysis to examine blood test changes from baseline to 24 weeks, the LFD group experienced a decrease in arterial blood pH from a mean of 7.43 at week 0 to 7.40 at week 24 (P ¼ 0.03), and the LCKD group experienced a decrease from 7.42 at week 0 to 7.40 at week 24 (P ¼ 0.01). The lowest pH measurements observed were 7.34 in the LFD group and 7.37 in the LCKD group. Although serum bicarbonate appeared to decrease from baseline at weeks 2 and 8 in the LCKD group, the change at 24 weeks was not statistically significant in either diet group, and only four of 131 (two of 92 from the LCKD group) measurements were less than 22 mmol/l. The proportion of participants with elevated urine and serum ketone body levels rose in the LCKD group only, was highest at week 2, and decreased over the subsequent time points. Conclusion: In individuals following an LCKD or an LFD, blood pH decreased mildly and the LCKD group experienced a small, transient decrease in serum bicarbonate in conjunction with mild ketosis. This suggests that an LCKD induced a mild compensated metabolic acidosis, but no individual showed evidence of significant metabolic derangement.

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The human metabolic response to chronic ketosis without caloric restriction: Physical and biochemical adaptation

Cited by 153 publications

References 31 publications

Failure of systemic ketosis to control cachexia and the growth rate of the Walker 256 carcinosarcoma in rats

Failure of systemic ketosis to control cachexia and the growth rate of the Walker 256 carcinosarcoma in rats

The ‘carnivore connection’—evolutionary aspects of insulin resistance

Acid-base analysis of individuals following two weight loss diets

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