Stephen Phinney

• MD, PhD
• Professor Emeritus at University of California, Davis

Demonstrates the major benefits of dietary carbohydrate restriction by reversing metabolic syndrome without weight loss in a 3-way randomized crossover study

Dietary treatment is important in management of type 2 diabetes or prediabetes, but uncertainty exists about the optimal diet. We randomized adults (n = 34) with glycated hemoglobin (HbA1c) > 6.0% and elevated body weight (BMI > 25) to a very low-carbohydrate ketogenic (LCK) diet (n = 16) or a moderate-carbohydrate, calorie-restricted, low-fat (MCC...

Background: Type 2 diabetes (T2D) is typically managed with a reduced fat diet plus glucose-lowering medications, the latter often promoting weight gain. Objective: We evaluated whether individuals with T2D could be taught by either on-site group or remote means to sustain adequate carbohydrate restriction to achieve nutritional ketosis as part of...

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 submaxi...

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 stud...

Abstract 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-a...

Objective: To examine circulating hormonal responses in men competing in the Western States Endurance Run (WSER, June 23 to 24, 2012): a 161-km trail run that starts in Squaw Valley, CA, and concludes in Auburn, CA. Methods: We examined 12 men who completed the WSER. Blood samples were obtained the morning before the race, immediately postrace (...

Exercise scientists teach that since muscle glycogen utilisation occurs at high rates (during high-intensity exercise in carbohydrate-adapted athletes), all athletes must be advised to ingest large amounts of carbohydrate before and during exercise.1 ,2 But this does not seem entirely logical. Why, for example, should athletes involved in prolonged...

The aim of this study was to examine coagulatory and fibrinolytic responses to the Western States Endurance Run (WSER, June 23 to 24, 2012). The WSER is a 161-km (100 mile) trail foot race through the Sierra Nevada Mountains that involves 6,030 m of climb and 7,001 m of descent. We examined 12 men and 4 women [mean (95 % CI), age 44.6 years (38.7-5...

Recent research results mandate a careful re‐evaluation of the widespread belief that dietary saturated fat is harmful. Specifically, multiple recent reports find no association between dietary saturated fat intakes and cardiovascular disease (CVD). There is, however, a consistent pattern of increased risk for both CVD and type‐2 diabetes associate...

We recently showed that 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). Here we extend these findings in 8 weight stable men who were...

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 carbohydra...

Oolichan grease, a dietary fat prepared from smelt-like fish, is highly prized by north Pacific coast aboriginal cultures. The composition of oolichan grease is unclear, with one report indicating a high 22:6n-3 content consistent with cold-water marine oils, but another reporting a much lower value. We noted that oolichan grease remains solid up t...

Abnormal fatty acid metabolism and dyslipidemia play an intimate role in the pathogenesis of metabolic syndrome and cardiovascular diseases. The availability of glucose and insulin predominate as upstream regulatory elements that operate through a collection of transcription factors to partition lipids toward anabolic pathways. The unraveling of th...

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 carboh...

Increased cardiovascular risk in hemodialysis patients may be related to augmented oxidative stress and inflammation, for which no proven beneficial therapies are available. We examined the effects of gamma tocopherol and docosahexaenoic acid (DHA) administration on inflammation and oxidative stress markers in hemodialysis patients in a randomized,...

The persistence of an epidemic of obesity and type 2 diabetes suggests that new nutritional strategies are needed if the epidemic is to be overcome. A promising nutritional approach suggested by this thematic review is carbohydrate restriction. Recent studies show that, under conditions of carbohydrate restriction, fuel sources shift from glucose a...

The purpose of this study was to determine whether gamma-linolenate (GLA) supplementation would suppress weight regain following major weight loss. Fifty formerly obese humans were randomized into a double-blind study and given either 890 mg/d of GLA (5 g/d borage oil) or 5 g/d olive oil (controls) for 1 y. Body weight and composition and adipose f...

Very low-calorie diets (VLCDs) have a history of cyclic popularity. Although a VLCD can be a very effective tool for the rapid mobilization of body fat, both the margin of safety and the efficacy of this class of diet are limited by their inherent calorie restriction. The result is a potent weight-management tool that requires close medical monitor...

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.

This study investigated the effects of a dietary supplement on exercise-induced markers of cell damage and the inflammatory mediators C-reactive protein (CRP) and interleukin-6 (IL-6). The supplement contained mixed tocopherols, flavonoids, and docosahexaenoate. Forty healthy, nonsmoking, untrained males (aged 18-35 yr) were randomly assigned to re...

The metabolism of alpha and gamma tocopherol, the major components of vitamin E, have not been studied in uremic patients. The major pathway of tocopherol metabolism is via phytyl side chain oxidation, leaving carboxyethyl-hydroxychromans (CEHC) as metabolites. Alpha and gamma CEHC are water soluble, renally excreted, with known potent anti-inflamm...

We examined, in young adult women, the association between current low dose oral contraceptive (OC) use and plasma levels of C-reactive protein (CRP), an acute phase reactant predictive of cardiovascular disease risk. We conducted a cross-sectional analysis of 30 healthy, non-smoking, non-obese women (18 OC users and 12 nonusers) who were subjects...

Although commercial weight loss programs provide treatment to millions of clients, their efficacy has not been evaluated in rigorous long-term trials. To compare weight loss and health benefits achieved and maintained through self-help weight loss vs with a structured commercial program. A 2-year, multicenter randomized clinical trial with clinic v...

Fourteen pairs of obese female monozygotic twins were recruited for a study of genetic influences on serum and adipose fatty acid (FA) composition. Following 1 wk of inpatient stabilization, fasting serum and adipose tissue obtained by surgical excision were analyzed by thin-layer and gas chromatography. Intrapair resemblances (IPR) for individual...

The metabolism of arachidonic acid (AA) has been shown to be altered in severe insulin resistance that is present in obese (fa/fa) Zucker rats. We examined the effects and mechanism of action of AA on basal and glucose-stimulated insulin secretion in pancreatic islets isolated from obese (fa/fa) Zucker rats and their homozygous lean (Fa/Fa) litterm...

Compared with the lean (Fa/-) genotype, obese (fa/fa) Zucker rats have a relative deficiency of muscle phospholipid arachidonate, and skeletal muscle arachidonate in humans is positively correlated with insulin sensitivity. To assess the hypothesis that the positive effects of exercise training on insulin sensitivity are mediated by increased muscl...

Circulating leptin decreases during fasting in rodents and humans; however, the mechanism of the decrease is unknown. The aim of this study was to examine the relationship between decrements of serum leptin concentrations and changes of hormonal (insulin and cortisol) and metabolic (glucose, ketones, and fatty acids) parameters involved in the meta...

The consequences of a 42 d exposure to elevated growth hormone (GH) on adipose tissue were assessed using the regulatable ovine metallothionein- ovine GH (oMt1a-oGH) transgene in male and female GH transgenic (TG) mice. Activation of transgene expression at 21 d of age followed by inactivation of transgene expression at 63 d of age (TG-on/off) incr...

Growth hormone (GH) has many metabolic effects, but its mechanism(s) of action are not fully understood. We studied the short-term effects of endogenously produced GH on liver delta 6-desaturase activity and adipose and liver lipid fraction fatty acid composition in transgenic mice. MG101 transgenic mice ages 73-114 d received zinc to activate the...

Protein-calorie malnutrition as evidenced by loss of weight or of lean body mass is a commonly seen disorder. Although its cause is clearly multifactorial, objective measures of protein-calorie malnutrition have been repeatedly correlated with poor patient outcomes. Total parenteral nutrition was developed to halt or reverse this disorder, but its...

Arachidonic acid is an important regulator of cellular function via its effects on the physical properties of membranes, in its free form, or as a substrate for eicosanoids. Dietary studies indicate that its production is regulated, but the mechanisms of this regulation and factors influencing arachidonate distribution from the site of production r...

Obesity continues to increase in prevalence, now affecting more than one third of the adult population of the United States. The health risks of obesity are proportional to increase in body mass index (weight in kilograms divided by the square of the height in meters), and include adult-onset diabetes, hypertension, hyperlipidemia and coronary arte...

Epidemiologic evidence in humans and controlled trials in animal models indicate that total dietary fat increases the risk of cancer. The animal evidence indicates that the greatest efficacy in promoting carcinogenesis is achieved with omega-6 fatty acids with little or no effect from either the omega-3 or monounsaturated fatty acid families. Epide...

Reduced fat intake may be beneficial in reducing coronary disease and cancer risk, but long-term outpatient trials are impeded by limited measures of subject adherence to a low fat intake. We sequentially obtained fàsting serum from 24 post-menopausal healthy women maintained on outpatient eucaloric diets after 4 wk at 31% energy as fat, after 6 wk...

Adipose tissue was obtained from six women undergoing liposuction twice at 6-mo intervals. Samples obtained bilaterally from abdomen, inner thigh, and outer thigh had fatty acids quantified by gas chromatography. There were no important differences between sides or over time. The saturates 14:0, 16:0, 18:0, and 20:0 were higher in abdominal adipose...

To determine whether there is altered liver lipid-fraction fatty acid distribution in a multigenic obese mouse model, we examined livers from eight lean (0.2-4.2% carcass fat), seven intermediate (5.7-13.8%), and five obese (20.2-48.7%) backcross progeny [(C57BL/6J x Mus spretus) x C57BL/6J] aged 2-3 mo. Thirteen males and seven females were fed a...

The micropig model of chronic alcoholism was used to study the relationship of lipid composition and physical properties in three different tissue membranes from the same animals. Ethanol feeding reduced membrane anisotropy, as measured with the diphenylhexatriene probe, in liver plasma and kidney brush-border membranes but not in jejunal brushbord...

This study investigated the mechanism by which chronic ethanol feeding reduces arachidonate and other highly unsaturated fatty acids in pig liver phospholipids. Five micropigs were fed a diet providing 89 kcal/kg body wt for 12 mo, with ethanol and fat as 40 and 34% of energy, respectively. Five control pigs were pairfed corn starch instead of etha...

Our previous research with miniature pigs has shown that long-term ethanol feeding with a low-fat diet decreases arachidonic acid (20:4 omega 6) levels in multiple tissues, but we did not find significant liver pathology. In this study, we investigated the effect of ethanol feeding with high dietary linoleic acid (18:2 omega 6) on tissue fatty acid...

We have previously reported that the relative content of 18:3 omega 3 in adipose triglyceride (TG) of women was reduced following major weight loss while on a very low calorie diet (VLCD). In an attempt to prevent this loss of 18:3 omega 3 reserves, we have tested two VLCD supplemented with varying amounts of 18:3 omega 3. The formula (FORM) and fo...

We have previously reported that the relative content of 18∶3ω3 in adipose triglyceride (TG) of women was reduced following major weight loss while on a very low calorie diet (VLCD). In an attempt to prevent this loss of 18∶3ω3 reserves, we have tested two VLCD supplemented with varying amounts of 18∶3ω3. The formula (FORM) and food VLCD (2.1–3.0 M...

Below-normal proportions of phospholipid (PL) arachidonic acid (20:4 omega 6) have been reported in serum from obese humans and in liver from obese Zucker rats. This implies an abnormality of 20:4 omega 6 formation from linoleic acid (18:2 omega 6), possibly in the delta 6 desaturase step, or alternatively an abnormality in the catabolism or distri...

Manifestations of essential fatty acid (EFA) deficiency in rats include growth retardation and increased transdermal water loss. The extra metabolic energy requirement could be caused by greater evaporative water loss from the skin surface. To test this hypothesis, 38 weanling rats were randomly assigned to one of two environments, control (CE) at...

Obese Zucker rats (fa/fa) have low levels of arachidonic acid (AA) in liver phospholipids (PL). We have previously shown that a 70% gamma-linolenate concentrate (GLA; an AA intermediate) fed at a fixed dose (0.07 g/day) normalized hepatic PL AA and reduced weight gain selectively in the obese animals. In a follow-up study, 16 obese (fa/fa) and 16 l...

There is a general consensus that the mortality rates for asthma in much of the developed world have been increasing for the past 10-15 years. This has occurred despite an improved information base regarding diagnosis and management as well as the development of novel and more effective therapeutic modalities. Several explanations have been propose...

The effect of ethanol feeding on the essential fatty acid content of tissues has been contradictory. To define the effect, we analyzed fatty acid profiles in various tissues from five miniature pigs fed daily 105 kJ basal diet/kg body wt and 146 kJ ethanol/kg body wt, and also five control pigs pair-fed the same amount of basal diet but with corn s...

Neither diet nor exercise are effective as single modes of intervention in the treatment of obesity. Although it is logical that they be combined in the context of multidisciplinary treatment, restrictions in calorie or protein intakes while dieting may impair short-term or long-term function. The limited evidence available indicates that properly...

The authors have previously shown that chronic ethanol feeding reduces arachidonic acid (AA) and other products of δ6 and δ5 desaturases in various tissues including muscle, the largest phospholipid (PL) pool. In this study they investigated the time-course effect of ethanol feeding on tissue fatty acid (FA) profiles. Five Yucatan micropigs were...

Serum lipoproteins, body composition, and adipose cholesterol contents of six obese women were studied during and after major weight loss by very-low-calorie diets (VLCDs). Subjects started at 168 +/- 11% of ideal body weight, lost 30.3 +/- 3.7 kg in 5-7 mo, followed by 2+ mo in weight maintenance. Serum cholesterol fell from a prediet (baseline) v...

In the miniature pig, ethanol consumption has been reported to induce alterations in hepatic antioxidant defense capacity, which could result in increased risk of peroxidative damage. However, ethanol may also induce changes in membrane fatty acid composition, which could reduce the risk of peroxidative damage. This study examined lipid peroxidatio...

Serum omega 6 (n-6) fatty acids were assessed in 12 obese women during an outpatient very-low-calorie diet (VLCD). Ten subjects (S10) achieved a mean weight loss of 17 kg over 3-5 mo (initial weight-for-height 157%). Serum was obtained before (baseline) and monthly during the VLCD and from five of them (S5) after 2-3 mo of weight stability (refed)...

The human undergoing rapid and sustained weight loss by very low calorie dieting (VLCD) derives the majority of daily energy needs from adipose fatty acids. To evaluate the rates of metabolic utilization of individual fatty acids in humans, two groups of adult women outpatients were studied during major weight loss by VLCD. The diets used were eith...

The authors have suggested that ethanol (Et) metabolism may evoke a protective response by the hepatic cell including changes in free radical defense and membrane fatty acid composition resulting in less peroxidizable membranes. To test this, micropigs were fed diets containing 40% of kcals as either Et or corn starch (C) and 30% of kcals as corn o...

The human undergoing rapid and sustained weight loss by very low calorie dieting (VLCD) derives the majority of daily energy needs from adipose fatty acids. To evaluate the rates of metabolic utilization of individual fatty acids in humans, two groups of adult women outpatients were studied during major weight loss by VLCD. The diets used were eith...

To determine the effects on physical performance of two different very low calorie diets (VLCD), 10 moderately obese women (BMI 32.7) were tested before and after an outpatient weight loss of 17 kg. Diet 1 (D1, n = 5) subjects lost 17.2 kg on 450-550 kcal/d from common food regimen adjusted for stature providing protein at 1.5 g/kg IBW and less tha...

We evaluated the differential effects of feeding two very-low-calorie diets upon the fractions of plasma and urinary carnitine in obese females. Ten subjects received either diet D1, a 420 kcal/day formula diet, or diet D2, a 500-600 kcal/day meat/fish/poultry diet. Plasma and urinary carnitine levels were determined at the start of the study. Afte...

Lipid fractions such as phospholipids (PLs), cholesteryl esters (CEs), and free fatty acids (FFAs) represent source pools for eicosanoid synthesis. To determine whether dietary habits affect the enrichment of 20:4n-6 in these precursor pools, we studied humans with partial or complete arachidonate restriction resulting from chronic avoidance of ani...

Aerobic exercise in addition to severe caloric restriction was studied for its effects on resting energy expenditure (REE), weight loss, and lean tissue preservation in adult women. A formula diet providing 1.5 g protein and 0.5 g carbohydrate (CHO) per kilogram of ideal body weight daily (mean intake 720 kcal/d) was given to 12 overweight inpatien...

The objective was to determine if dietary fish oil decreased the degree of fatty acid saturation in rat lung phosphatidylcholine (PC). A diet containing 12% of its energy as fat was fed for 3 wk to growing male Sprague-Dawley rats (trial I) or to pregnant rats for days 8-21 of gestation (trial II). The dietary fat treatments in trial I were safflow...

The objective of these studies with rat hepatocytes in primary culture was to establish that: (a) membrane phospholipids would become enriched with the specific fatty acid supplemented to the media and (b) hepatocyte monolayer triacylglycerol synthetic rates were dependent on the type of fatty acid enrichment of the membrane phospholipids. Hepatocy...

The effects of diet on the serum concentrations of albumin, transferrin, thyroxine-binding prealbumin (TBPA) and retinol-binding protein (RBP) were studied in 3 groups of obese subjects (Groups I–III) and 1 group of normal weight subjects (Group IV). Group I subjects ate either a 830 kcal carbohydrate-containing diet (CCD) or carbohydrate-restricte...

To study the capacity for moderate endurance exercise and change in metabolic fuel utilization during adaptation to a ketogenic diet, six moderately obese, untrained subjects were fed a eucaloric, balanced diet (base line) for 2 wk, followed by 6 wk of a protein-supplemented fast (PSF), which provided 1.2 g of protein/kg ideal body wt, supplemented...

For the past several decades, treatment of primary hypertension has relied chiefly upon the use of pharmacologic agents. Many hypertensive patients are obese. Evidence is accumulating that their hypertension may be reversed by aggressive and comprehensive regimens for weight reduction. Controlled studies are needed to determine whether there may be...

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 (~1,500kcal): a carbohydrate-restricted...