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On Starvation and Obesity, with Special Reference to Acidosis
... In 1915, fasting therapy for obesity was described by Folin & Denis [5]. Repeated short periods of fasting were proposed as a safe and effective method of weight reduction [5]. ...
... In 1915, fasting therapy for obesity was described by Folin & Denis [5]. Repeated short periods of fasting were proposed as a safe and effective method of weight reduction [5]. Many obese followers have experienced different regimens of fasting for as much as 100 days or more. ...
Since ancient days, human fasting has been performed for religious or political reasons. More recently, fasting has been employed as an effective therapy for weight reduction by obese people, and numerous studies have investigated the physiology of fasting by obese subjects. Well-established fasting markers (butyrates, BCAAs and carnitines) were considered essential energy substitutes after glycogen storage depletion. However, a recently developed metabolomic approach has unravelled previously unappreciated aspects of fasting. Surprisingly, one-third (44) of 120 metabolites investigated increase during 58 h of fasting, including antioxidative metabolites (carnosine, ophthalmic acid, ergothioneine and urates) and metabolites of entire pathways, such as the pentose phosphate pathway. Signalling metabolites (3-hydroxybutyrate and 2-oxoglutarate) and purines/pyrimidines may also serve as transcriptional modulators. Thus, prolonged fasting activates both global catabolism and anabolism, reprogramming metabolic homeostasis.
... Scientific research on the biomedical effects of fasting was performed from the late nineteenth century on, when several non-obese humans fasted for 20-40 days [26]. The first clinical study of medical fasting for the treatment of obesity was performed in 1915 [109]. The authors reported that short periods of four to six days of fasting is a safe and effective method for reducing bodyweight in obese humans. ...
... Fasting therapy was observed to be generally safe and well tolerated. Only mild side effects were reported, including headaches, dizziness, nausea, dyspepsia and fatigue [109][110][111][112][113][114]. However, in rare cases fasting for periods longer than 2 weeks was fatal in obese subjects with comorbidities as cardiac disease or diabetes mellitus [26,[115][116][117], and in one rare case a 53-day fast caused Wernicke encephalopathy in a patient with a lymphoma [118]. ...
Growing preclinical evidence shows that short-term fasting (STF) protects from toxicity while enhancing the efficacy of a variety of chemotherapeutic agents in the treatment of various tumour types. STF reinforces stress resistance of healthy cells, while tumor cells become even more sensitive to toxins, perhaps through shortage of nutrients to satisfy their needs in the context of high proliferation rates and/or loss of flexibility to respond to extreme circumstances. In humans, STF may be a feasible approach to enhance the efficacy and tolerability of chemotherapy. Clinical research evaluating the potential of STF is in its infancy. This review focuses on the molecular background, current knowledge and clinical trials evaluating the effects of STF in cancer treatment. Preliminary data show that STF is safe, but challenging in cancer patients receiving chemotherapy. Ongoing clinical trials need to unravel if STF can also diminish toxicity and increase efficacy of chemotherapeutic regimes in daily practice.
... Polyphenol content was determined in extract prepared using hot water, following the protocol laid by Folin and Denis (1915). Tannic acid was used to make a linear calibration curve and the results were expressed as mg TAE (tannic acid equivalent) per plant. ...
Over the last few decades, buckwheat (Fagopyrum sp.) and barley (Hordeum sp.) have attracted attention of food scientists because of their high nutritional value and increased demand. In trans-Himalaya region, where they are major grain crops, limited information on their cultivation and uses has been documented. The study aimed to determine the nutritional and phytochemical composition of Fagopyrum tataricum, F. esculentum, Hordeum vulgare and H. himalayens cultivated in the trans-Himalaya region along with a self-sustaining wild population of Fagopyrum sp. wild variety, commonly observed from this less traversed region of India. Results indicated significant variation in the nutritional values including total carbohydrates, starch, and protein contents among these crops. Each species had a unique profile that can be accounted for its proper nutritional and economic use. Mineral composition varied among the Fagopyrum species with most significant difference found for the content of calcium, iron and sodium. Quantification of phenols, flavonoids, and total polyphenols showed variation among the varieties of the same crop species. Gas chromatography mass spectrometry indicated 26, 33, and 15 compounds present in grains of F. tataricum, F. esculentum, and F. sp. wild variety, respectively. H. vulgare and H. himalayens had 26 and 32 compounds, respectively. All these compounds belong to diverse functional groups. Heat maps also illustrated the variable concentration of these compound classes in the grains. Our results indicated that these landraces are rich in nutrients, antioxidants and other phytochemicals, highlighting their great potential as nutraceutical foods. Among the crops considered in our study, the species, F. tataricum and H. himalayens hold great potential for cultivation as nutrient rich crops that can be grown in cold deserts of the Himalayan belt. These crops are adapted to low temperatures and can grow well at high altitudes and various kinds of environmental stress conditions. The study encourages the use of these functional foods as an excellent supplement or replacement for better health choices.
... In line with isocaloric PF, FMD last 2 or more days and are interspersed with at least 7 days of ad libitum feeding. The therapeutic interest in IF and PF is not an entirely new concept with Otto Folin and W. Denis demonstrating in 1915 that prolonged fasting ameliorated obesity and metabolic syndrome (141). Although recent studies have re-emphasized the therapeutic benefits of fasting, the molecular mechanisms underlying beneficial effects of these diets on the islet are only starting to be elucidated more than 100 years later. ...
Our ever-changing modern environment is a significant contributor to the increased prevalence of many chronic diseases, and particularly, type 2 diabetes mellitus (T2DM). Although the modern era has ushered in numerous changes to our daily living conditions, changes in “what” and “when” we eat appear to disproportionately fuel the rise of T2DM. The pancreatic islet is a key biological controller of an organism’s glucose homeostasis and thus plays an outsized role to coordinate the response to environmental factors to preserve euglycemia through a delicate balance of endocrine outputs. Both successful and failed adaptation to dynamic environmental stimuli has been postulated to occur due to changes in the transcriptional and epigenetic regulation of pathways associated with islet secretory function and survival. Therefore, in this review we examined and evaluated the current evidence elucidating the key epigenetic mechanisms and transcriptional programs underlying the islet’s coordinated response to the interaction between the timing and the composition of dietary nutrients common to modern lifestyles. With the explosion of next generation sequencing, along with the development of novel informatic and –omic approaches, future work will continue to unravel the environmental-epigenetic relationship in islet biology with the goal of identifying transcriptional and epigenetic targets associated with islet perturbations in T2DM.
... Fasting was speculated to have a host of benefits as early as 1915 when Otto Folin recommended short periods of starvation as an effective means to reduce weight in obese individuals. (1) In 1946, Anton Carlson coined the term 'intermittent fasting' when investigating its effect on longevity in rats. (2) Carlson also noted that many religious individuals historically attributed their long lifespan to periodically abstaining from food. ...
Background
Low-density lipoprotein cholesterol (LDL-C) predicts heart disease onset and may be reduced by intermittent fasting. Some studies, though, reported that fasting increased LDL-C; however, no study evaluated LDL-C as the primary endpoint. This randomized controlled trial evaluated the effect of low-frequency intermittent fasting on LDL-C and other biomarkers.
Methods
Adults ages 21-70 years were enrolled who were not taking a statin, had modestly elevated LDL-C, had ≥1 metabolic syndrome feature or type 2 diabetes, and were not taking anti-diabetic medication (N = 103). Water-only 24-hour fasting was performed twice-weekly for 4 weeks, then once-weekly for 22 weeks; controls ate ad libitum. The primary outcome was 26-week LDL-C change score. Secondary outcomes (requiring p ≤ 0.01) were 26-week changes in homeostatic model assessment of insulin resistance (HOMA-IR), Metabolic Syndrome Score (MSS), brain-derived neurotrophic factor (BDNF), and MicroCog general cognitive proficiency index (GCPi).
Results
Intermittent fasting (n = 50) and control (n = 53) subjects were, respectively, aged 49.3±12.0 and 47.0±9.8 years, predominantly female (66.0% & 67.9%), overweight (103±24 & 100±21 kg), and had modest LDL-C elevation (124±19 & 128±20 mg/dL). Drop-outs (n = 12 fasting, n = 20 control) provided an evaluable sample of n = 71 (n = 38 fasting, n = 33 control). Intermittent fasting did not change LDL-C (0.2±16.7 mg/dL) versus control (2.5±19.4 mg/dL; p = 0.59), but it improved HOMA-IR (-0.75±0.79 vs. -0.10±1.06; p = 0.004) and MSS (-0.34±4.72 vs. 0.31±1.98, p = 0.006). BDNF (p = 0.58), GCPi (p = 0.17), and weight (-1.7±4.7 kg vs. 0.2±3.5 kg, p = 0.06) were unchanged.
Conclusions
A low-frequency intermittent fasting regimen did not reduce LDL-C or improve cognitive function, but significantly reduced both HOMA-IR and MSS.
Trial registration
clinicaltrials.gov, NCT02770313
... The key metabolic changes during fasting were quantified in 1915 by Folin and Denis. They studied two morbidly obese subjects who underwent intermittent total fasts lasting between 3 and 6 days and demonstrated that betahydroxybutyric acid was the major excreted organic acid in the urine and that with successive fasts there was a metabolic adaptation with decreased urinary nitrogen excretion [67]. ...
Protein sparing therapies were developed to mitigate the harms associated with protein-calorie malnutrition and nitrogen losses induced by either acute illness or hypocaloric diets in patients with obesity. We review the development of protein sparing therapies in illness and obesity with a focus on the pioneering contributions of George Blackburn, MD, PhD. He recognized that protein-calorie malnutrition is a common and serious clinical condition and developed new approaches to its treatment in hospitalized patients. His work with stable isotopes and with animal models provided answers about the physiological nutritional requirements and metabolic changes across a spectrum of conditions with varying degrees of stress and catabolism. This led to improvements in enteral and parenteral nutrition for patients with acute illness. Blackburn also demonstrated that lean body mass can be preserved during weight loss with carefully designed very low calorie treatments which became known as the protein sparing modified fast (PSMF). We review the role of the PSMF as part of the comprehensive management of obesity.
... Metabolic changes due to fasting in humans were first investigated in the beginning of the century for treating obesity and other conditions, such as seizure disorders. [32][33][34] Kerndt et al. investigated the metabolic effects of long-term fasting in human subjects who underwent a 36-day complete fasting regimen for religious reasons. 35 They noted a significant decrease in blood pressure, reaching significance on the 33rd day, accompanied by negative sodium balance. ...
This review analyzes the available literature on the impact of intermittent fasting (IF), a nutritional intervention, on different aspects of metabolism. The epidemic of metabolic disturbances, such as obesity, metabolic syndrome (MS), and diabetes mellitus type 2 has led to an increase in the prevalence of cardiovascular diseases, and affected patients might significantly benefit from modifications in nutritional habits. Recent experimental studies have elucidated some of the metabolic mechanisms involved with IF. Animal models have shown positive changes in glucose (lower plasma glucose and insulin levels) and in lipid metabolism (reduced visceral fat tissue and increased plasma adiponectin level), and an increased resistance to stress. Despite the limited number of samples studied, positive results have been reported on the impact of IF for human health. IF is reported to improve the lipid profile; to decrease inflammatory responses, reflected by changes in serum adipokine levels; and to change the expression of genes related to inflammatory response and other factors. Studies on obese individuals have shown that patient compliance was greater for IF than other traditional nutritional approaches (calorie restriction), and IF was found to be associated with low oxidative stress. Recent reports suggest that IF exerts a positive impact on the metabolic derangements commonly associated with cardiovascular diseases, and that it may be a viable and accessible intervention for most individuals. Therefore, further clinical studies are essential to test the effectiveness of IF in preventing and controlling metabolic and cardiovascular diseases.
... There is a pronounced increase on the 6th and 7th days to a level approximating more nearly that reported by previous investigators (4,5). The total volume and the creatinine determinations for the 5th day point to a probable loss of urine. ...
... In addition to people starving themselves to death, very often in the past people have starved themselves for protracted periods with the aim of losing weight (Johnstone, 2007). This 'therapeutic fasting' as a treatment for obesity was initially advocated by Folin and Denis (Folin and Denis, 1915) and Benedict (Benedict, 1915), but was not widely adopted until it and was picked up by Bloom (Bloom, 1959). During the early 1960s it was common for obese people to be placed on 12-to 16-day fasts to lose body weight (e.g. ...
The thrifty gene hypothesis (TGH) posits that the modern genetic predisposition to obesity stems from a historical past where famine selected for genes that promote efficient fat deposition. It has been previously argued that such a scenario is unfeasible because under such strong selection any gene favouring fat deposition would rapidly move to fixation. Hence we should all be predisposed to obesity: which we are not. The genetic architecture of obesity that has been revealed by genome wide association studies (GWAS), however, calls into question such an argument. Obesity is caused by mutations in many hundreds (maybe thousands) of genes each of very minor, independent and additive impact. Selection on such genes would likely be very weak as the individual advantages they would confer would be very small. Hence the genetic architecture of the epidemic may indeed be compatible with, and hence support, the TGH. To evaluate if this is correct it is necessary to know the likely effects of the identified GWAS alleles on survival during starvation. This would allow definition of their advantage in famine conditions, and hence the likely selection pressure for such alleles to have spread over the time course of human evolution. We constructed a mathematical model of weight loss under total starvation using the established principles of energy balance. Using the model we found that fatter individuals would indeed survive longer, and at a given body weight females would survive longer than males, when totally starved. An allele causing deposition of an extra 80g of fat would result in an extension of life under total starvation by about 1.1 to 1.6% in an individual with 10 kg of fat and by 0.25 to 0.27% in an individual carrying 32kg of fat. A mutation causing a per allele effect of 0.25% would become completely fixed in a population with an effective size of 5 million individuals in 6000 selection events. Since there have probably been about 24000 famine events since the evolution of hominins 4 million years ago, there has been ample time even for genes with only very minor impacts on adiposity to move to fixation. The observed polymorphic variation in the genes causing the predisposition to obesity is incompatible with the thrifty gene hypothesis, unless all these single nucleotide polymorphisms (SNPs) arose in the last 900,000 years, a requirement we know is incorrect. The TGH is further weakened by the observation of no link between the effect size of these SNPs and their prevalence, which would be anticipated under the TGH model of selection if all the SNPs had arisen in the last 900,000 years.
... Starvation of obese patients, however, may be dated much earlier in the century. Folin and Denis noted that the two obese women whom they studied during short fasts lost less nitrogen than leaner subjects under similar conditions, indicating that they were more effective in conserving protein (18). The most comprehensive studies of fasting and inanition were published by Benedict (2,3). ...
... Although the systematic study of the metabolic effects of starvation began nearly a century ago (6,7), the molecular basis of metabolic interrelationships during fasting or starvation has not been completely delineated. Changes in metabolism that occur during the starvation-feeding cycle provide one approach to understanding the relationships of the metabolic pathways. ...
ይህን መጽሀፍ ለምን ለመተርጎም ወሰንኩ?
እኔ ዶ/ር ዘውዱ ወንዲፍራው የደ/ማረቆስ ዩኒቨርስቲ ባለደረባ ስሆን በ2008 ዓ.ም ጥቅምት ወር መጀመሪያ አካባቢ ከፍተኛ የውሃ ጥም፣ በተደጋጋሚ ከፍተኛ መጠን ያለው ሽንት መሽናት፣ የሰውነት የድካም ስሜት፣ ብዥ የሚል ዕይታና የትኩረት ማጣት ችግሮች በአንድ ዕለት ሌሊት ተከሰቱብኝ፡፡ ዕለቱ እንደጠባ ጧት ሆስፒታል ሄድኩ የደም የስኳር መጠኔን ተመረመርኩ ምግብ ሳልወስድ 280 mg/dl ሆኖ አገኘሁት፡፡ በጣም የገረመኝ ከዚያ በፊት አንድም ቀን እንኳ ስለስኳር በሽታ አስቤ የቅድሚያ ምርመራ አለማድረጌ ነው፡፡ በወቅቱ የሰውነት ክብደቴ 82 ኪ.ግ ነበር፡፡ ቁመቴ 1 ሜትር ከ65 ሳ.ሜ ሲሆን በሰውነት ክብደት መረጃ ጠቋሚ መሰረት 30.12 ነበርኩ ይህም በሰውነት ክብደት ምደባዎች አማካኝነት ከልክ ያለፈ የሰውነት ውፍረት ነበረኝ ማለት ነው፡፡ ከምርመራ በኋላ ሁለት አይነት በአፍ የሚወሰዱ መድሃኒቶችን ማለትም ሜትፎርሚንና ዳይዎኔል የሚባሉትን መድሃኒቶችን እንድወስድ ሀኪሙ አዘዘልኝ፡፡ የታዘዙትን መድሃኒቶች ለ 10 ተካታታይ ቀናት ወስጄ አቋረጥኩ፡፡ ምክንያቱም አዕምሮዬ በፍጹም የህይወት ዘመን የስኳር በሽተኛ መሆንን ሊቀበለው አልቻለም፡፡
በምትኩ በሳምንት 4 ቀናት ለአንድ ስዓት ያህል ጠንከር ያለ የአካል ብቃት እንቅስቃሴ ለ4 ተከታታይ አመታት ያለማቋረጥ መስራት ጀመርኩ፡፡ በተጨማሪም ዝቅተኛ የካሮቦሃይድሬት ይዘት ያላቸውን ምግቦች ብቻ መመገብ ጀመርኩ እንዲሁም አልፎ አልፎ ጧት ላይ ቁርስ መብላቴን አቆምኩ፡፡ ምንም አይነት አልኮሆል መጠጣቴን አቋረጥኩ፡፡ በዚህም ምክንያት የደም ስኳሬ መጠን እየተስተካከለ መጣ ከመነሻው ከ280 mg/dl ወደ 114 mg/dl ወይም 5.6% የሂሞግሎቢን ኤዋንሲ የተረጋጋ ውጤት ደረሰ፡፡ የሰውነቴ ክብደት በአራት አመት ጊዜ ውስጥ 14 ኪ.ግ. በመቀነስ 68 ኪ.ግ. ደረሰ፡፡ አሁን የቀነስኩትንም ክብደት በዘለቄታው አስጠብቄያለሁ፡፡ በዕየለቱ በውስጤ ደስታና ቀለል የሚል ስሜት እንዲሁም የበለጠ የሰውነት ብርታትና ጥንካሬ ይሰማኛል፡፡
ከዚሁ እንቅስቃሴ ጎን ለጎን ስለ ስኳር በሽታ ከኢንተርኔት ላይ መጽሃፍትን፣ የምርምር ወረቀቶችን፣ ቪዲዮዎችን ማንበብና ማዳመጥ ጀመርኩ፡፡ እነዚህን ሁሉ መረጃዎች ሳገናዝብ የሁለተኛው አይነት የስኳር በሽታ ሊድን የሚችል በሽታ እንደሆነና በርካታ ሰዎችም ከበሽታው እንደተፈወሱ ብዙ መረጃዎችን ለማየት ሞከርኩ፡፡ በዚህ ረገድ ካናዳ ቶሮንቶ ከተማ ውስጥ ጥብቅ የሆነ የአመጋገብ ቁጥጥር በማድረግ የሁለተኛው አይነት የስኳር በሽታ ያለባቸውን ህሙማን የሚያክም ዶ/ር ጀሰን ፈንግ የሚባል የኩላሊት ሀኪም መኖሩን ከድረ-ገጽ መረጃ አገኘሁ፡፡ እርሱም በዚሁ በሽታ ዙሪያ በርካታ የህዝብ ንግግሮችን ያደረገ ሲሆን መጽሃፍትንም ጽፏል፡፡ እርሱ ከጻፋቸው መጽሃፍት ውስጥ The-Diabetes-Code and The-Obesity-Code ዋናዎቹ ናቸው፡፡ ስለሆነም The-Diabetes-Code የተሰኘውን መጽሃፍ በዶ/ር ሩቅያ ሀሰን አማካኝነት ወደ አማርኛ “የስኳር በሽታ ቁልፍ” በሚል ርዕስ ተተርጉሞ አሁን በኢትዮጵያ ገበያ ላይ የሚገኝ ሲሆን እኔም በእርሷ የስራ ትጋት መነሻነት The-Obesity-Code የሚለውን መጽሃፍ ወደ አማርኛ “የሰውነት ውፍረትን የሚያመጡ ሚስጥራዊ እውነታዎች” በሚል ርዕስ ለመተርጎም ወሰንኩ፡፡ ይህ መጽሃፍ አማዞን በተሰኘው የድረ ገጽ መጽሃፍ መደብር ውሰጥ ከፍተኛ ሽያጭ ያሰገኘ ሲሆን እኔም ለኢትዮጵያዊያን ወገኖቼ በሚረዱት ቋንቋ ቢቀርብላቸው በርካቶች እንደእኔ ሊጠቀሙበት ይችላሉ ብዬ በማሰብ ለመተርጎም ችያለሁ፡፡
በዚህ መጽሃፍ ውስጥ ለሁለተኛው አይነት የስኳር በሽታ መሰረታዊ መንስኤ ከልክ ያለፈ የሰውነት ውፍረት መሆኑን ዶ/ር ፈንግ በዝርዝር ያስረዳል፡፡ ስለሆነም ምክንያታዊ በሆነ መልኩ የሰውነት ውፍረት ወሳኝ ትኩረት ያስፈልገዋል የሚል እምነት አለው፡፡ ብሎም ከልክ ያለፈ የሰውነት ውፍረት እና ሁለተኛው ዓይነት የስኳር በሽታ ብዙ ጠቃሚ የሆኑ ተመሳሳነትና ልዩነት እንዳላቸው ያሳያል፡፡ ኢንሱሊን በሰውነት ክብደት ውስጥ ያለውን ማዕከላዊ ሚና እንዲሁም የሰውነት የኢንሱሊን መቋቋም ችግር በሰውነት ክብደት ውስጥ የሚጫወተውን ወሳኝ ሚና በሚገባ ያስረዳል፡፡ በመጽኃፉም የሰውነት የኢንሱሊን መጠን የመጨመር ችግርን በመቆጣጠር ከልክ ያለፈ የሰውነት ውፍረትን መከላከል የሚያስችሉ መመሪያዎችን ይሰጣል፡፡ የአመጋገብ መመሪያዎች ኢንሱሊንን ለመቀነስ በተለይ የስኳር እና የተጣሩ የሰብል ውጤቶችን በመቀነስ፤ የፕሮቲንን ፍጆታ የተመጣጠነ እንዲሆን በማድረግ እና የጤናማ ስብ እና የአሰርን ፍጆታ በመጨመር ማስተካከል እንደሚቻል ይገልጸል፡፡ የካሎሪ ቅነሳ በሰውነት ጤንነት ላይ አሉታዊ ተጽዕኖ ሳያስከትል ጠንካራ ጾም በመጾም የሰውነት የኢንሱሊን የመቋቋም ችግር የሚያሰከትለውን አሉታዊ የሆነ ወሳኝ ሚና ለማስተካከል ውጤታማ መንገድ መሆኑን ያስረዳል፡፡ በመጽሐፉ ውስጥ ደራሲው በሰዎች ላይ የተደረጉ ጥናቶችን እና በአብዛኛው በታዋቂ ባለሙያዎች ተገምግመው በከፍተኛ ጥራት በሚታወቁ ጆርናሎች የታተሙትን ከ450 በላይ የምርምር ግኝቶችን እንደዋቢነት ተጠቅሟል፡፡
ስለሆነም ለኢትዮጵያዊያን ወገኖቼ መግለጽ የምፈልገው ይህ መጽሃፍ የእኔን ተስፋና ህይወት ቀይሮታል በዚህም መሰረት ይህ ችግር ያለባቸውን ሰዎች ህይወት ይቀይራል ብየ በጽኑ አምናለሁ፡፡ ስለዚህ ከልክ ያለፈ የሰውነት ውፍረትና የሁለተኛው አይነት የስኳር በሽታ ያላባቸውም ሆነ የሌለባቸው ሰዎች መጽሃፉን አግኝተው ቢያነቡት ብዙ ጠቃሚ መረጃ ያገኛሉ ብዬ በእጅጉ አምናለሁ፡፡
This article reassesses historical studies of Inuit metabolism in light of recent developments in evolutionary genetics. It discusses the possible selective advantage of a variant of CPT1a, which encodes the rate limiting enzyme in hepatic fatty acid oxidation. The L479 variant of CPT1a underwent one of the strongest known selective sweeps in human history and is specific to Inuit and Yu'pik populations. Recent hypotheses predict that this variant may have been selected in response to possible detrimental effects of chronic ketosis in communities with very low carbohydrate consumption. Assessing these hypotheses alongside several alternative explanations of the selective sweep, this article challenges the notion that the selection of L479 is linked to predicted detrimental effects of ketosis. Bringing together for the first time data from biochemical, metabolic, and physiological studies inside and outside the Inuit sphere, it aims to provide a broader interpretative framework and a more comprehensive way to understand the selective sweep. It suggests that L479 may have provided a selective advantage in glucose conservation as part of a metabolic adaptation to very low carbohydrate and high protein consumption, but not necessarily a ketogenic state, in an extremely cold environment. A high intake of n-3 fatty acids may be linked to selection through the mitigation of a detrimental effect of the mutation that arises in the fasted state. The implications of these conclusions for our broader understanding of very low carbohydrate metabolism, and for dietary recommendations for Inuit and non-Inuit populations, are discussed.
Success of any diet therapy depends on many factors other than the diet itself, which is often a minor consideration. Without strong motivation, interest of the physician or his assistant, frequent attendance at clinics, the outlook for the patient can be very poor. Nevertheless, one can speculate on the maximum amount of weight loss which can be achieved 1. Assuming that the loss of lean body mass is small, and that an average patient requires 2500 kcal/day, the weekly calorie deficit on total starvation would be 17 500 kcalories. Each kg of fat is equivalent to approximately 9000 kcalories so that the maximum weight loss could not be greater than 2 kg (4.4 lb) per week. On a diet of 1250 kcal/day, the theoretical loss is half this, namely 1 kg/week. Similar calculations can be made for diets of other calorific values. Since most diets are low in carbohydrate, the initial one to two weeks is accompanied by a loss of body water of about 3 kg; a factor of some psychological importance for the patient4(see Chapter 1).
Acne vulgaris is the most common disease of the skin. Obesity is arguably the commonest of a clinical entities in affluent societies. The pathogenesis of these disorders is far from clear cut and they appear to have little in common. In the present paper it is hypothesized that the pathogenesis of both ache vulgaris and obesity is largely due to a relative deficiency of the same agent, pantothenic acid, a vitamin that is hitherto quite unknown to cause any deficiency syndromes in man. Furthermore, the evidence suggests that surprisingly large doses of pantothenic acid are required to overcome deficiency states as illustrated in the treatment of acne vulgaris and obesity.
Fasting and starvation (prolonged fasting), are the most severe forms of malnutrition, and are experienced by aquatic and terrestrial species due to physiological, nutritional, or behavioral constraints. Migration, metamorphosis, reproduction, and molting are among the main endogenous factors, while food paucity, unpredictable feeding times, remote feeding grounds, and environmental and climatic changes are other external but similarly decisive cues. When the critical starving period is over, it can necessitate gradual refeeding, induce nutritional shifts, and also induce permanent damage. It has, therefore, always been a goal in physiology to understand the different adjustments during food deprivation and refeeding phases. In this field, most of the studies focusing on the physiological consequences of the imbalance between energy intake and energy expenditure have considered time to be the main function. However, since the late 1970s/early 1980s and the "rediscovery" of earlier studies, some researchers have considered starvation to be a continuous series of different metabolic phases composed of a short initial period of adaptation followed by a second phase characterized by fat oxidation. At this point, body lipid stores are not fully exhausted and a third nonpathological and reversible phase follows during which energy requirements are mostly derived from increased protein utilization. If prolonged, this phase can lead to a critical lethal endpoint, even if food becomes available. More recent studies have investigated the alarm signal that triggers behavioral changes such as nest abandonment and refeeding, and have also examined complex hormonal and metabolic regulations in response to food deprivation, such as the marked reduction of apolipoprotein A-IV levels observed in rodents during long-term fasting. The new challenges in this field concern the severely disrupted populations faced with increasing food restrictions due to anthropization.
Summary
1.
In the treatment of diabetes mellitus one should strive not merely to keep a patient comfortable and free from insulin reactions
but also to control his diabetic state, namely his hyperglycemia.
2.
By the control of hyperglycemia, we automati cally control all the other factors (glycosuria, ketonuria, weight, etc.).
3.
Hyperglycemia has a deleterious effect on a diabetic state which thus becomes progressive and a more severe diabetic state
results.
4.
For the proper control of any diabetic condition, one needs extensive daily blood sugar studies which alone will enable one
to distribute the insulin dosage wisely and adequately. Without such studies one has to work in the dark and do much guessing,
and that usually at the patient’s expense.
Human plasma albumin and S35-labeled glutathione mixtures yield radioactive polypeptides when incubated with cathepsin at pH 3.6. The results show that substantial amounts of glutathione are incorporated in the products of hydrolysis of albumin. These results and those previously reported concerning the formation of albumin-GSH mixed disulfides at low pH suggest that GSH plays an important role in modifying the substrate and in rendering it susceptible to catheptic hydrolysis.
The implications of these findings and their possible significance in intracellular protein catabolism are discussed.
Five people, free of any organic gastro-intestinal disease, were studied by repeated fractional gastric analysis following
meals of distilled water, a pure carbohydrate, a pure protein, and mixtures of the two. Four had a normal gastric acid response
and one was an achlorhydric. The studies were done in order to test the validity of the claims made that mixtures of protein
and carbohydrate interfere with proper gastric digestion. The gastric secretory studies included the usual titration of acidity
to Topfer’s and to phenolphthalein, hydrogen ion determinations, total chlorides, and quantitative pepsin. Gastric digestion
was followed by quantitative determinations of reducing substances and amino-nitrogen in the separate fractions. More than
6,000 determinations were made on over 900 fractional specimens in the course of the studies. The results showed that:
(1) Mixtures of carbohydrate and protein in the test meal do not, in any way, interfere with gastric secretion.
(2) Not only do these mixtures not interfere with gastric digestion,but that carbohydrate digestion in the stomach is prolonged and encouraged by its mixture with protein. This is probably brought about by the more favorable reaction for continued ptyalin activity in the stomach as a result
of the acid combining power of the protein. The same would be true following any regurgitation of pancreatic amylase from
the duodenum.
Observations on three obese persons on starvation diets are reported. Older findings about the rate of weight loss, reduction
of the basal caloric requirement, the behavior of the respiratory quotient, the acid-base balance and the ketobody excretion
have been confirmed. The effect of insulin on the non-diabetic ketosis has been demonstrated. The fat metabolism in starvation
has been discussed and it has been found that Stadie’s theory of a utilization limit for fat and a threshold for ketosis is
compatible with observations on starvation ketosis. The still remaining differences between starvation ketosis and diabetic
ketosis are emphasized.
The degree of ketonemia is a better measure of the degree of ketosis than is the ketonuria.
In obese patients the ketonemia following a fat meal is generally higher than in non-obese patients. This may be due to the
easier development of ketosis in obese subjects although this view is not supported by the conclusions in the literature.
Some obese patients develop no more ketonemia following a fat meal than do the majority of non-obese patients and some normals
develop a ketonemia of the obese type. Reasons for this are discussed.
The evidence at the present time does not support the view that fat tolerance tests may aid in the diagnosis of pituitary
disease.
Rats made obese by fat feeding have been shown to have a lower urinary mitrogen excretion when fasting than non-obese animals (1). However, it is not clear whether this reduced metabolism of protien is the effect (2) or the cause (3) of the obese state nor are its implications understood. We report here that the induction of obesity by cafeteria feeding in rats is also assosited with a lower fasting urinary nitrogen loss (FUNL) than relative to matched non-obese controls and that these changes are paralled by changes in obligatory nitrogen loss (ONL) of the animals when fed a protein free diet. Our results suggest that the reduced net nitrogen losses are a consequence of obesity and, since ONL is the dominant component of the protein requirements, that obese subjects may have a reduced protein requirement as well as a lower propensity to catabolise protein when fasting. Thus, the adiposity of the subject may need to be considered when estimates of protein requirement are made.
The published results of various dietary and medical treatments of obesity are analyzed and discussed. The reviewed dietary treatments include: balanced, low carbohydrate, formula and “one predominant food” diets as well as various less common diets. Diets which have become popular during the last few years, such as Dr. Stillman's and Dr. Atkins' have been reviewed in detail and their rationale has been critically assessed. The medical treatments reviewed in the article include: bulk producing agents, diet clubs and groups, psychotherapy (including behavior modification), medicinal and hormonal preparations (oral and injectable), exercise and surgical treatment (lipectomy and small bowel bypass).
In the normal human body, the extracellular fluid pH of 7.40 is closely protected. Any increase in acidity or alkalinity summons forth three lines of defense, starting immediately with the blood buffers, followed soon by the respiratory system's control of CO2, and finally purged by the renal excretion of the excess acid or base. The complex interrelated processes of the renal responses require a few days to accomplish maximum compensation. We have presented the fundamental principles governing maintenance of the acid-base equilibrium to provide a conceptual framework for understanding the clinical disorders of hydrogen ion metabolism.
The somewhat elusive concepts of endogenous acid production and net acid balance have also been reviewed to help reveal the pathophysiology of metabolic acidosis caused by renal tubular acidosis, chronic renal failure, certain infant feedings, and total parenteral nutrition. The development and perpetuation of metabolic alkalosis in relationship to chloride and potassium deficiency have been examined.
In the delineation of a clinical acid-base disorder, the clinician must bear in mind the continual interactions of electrolytes and hormonal systems and should be prepared to reevaluate frequently the elected therapy against the changing responses, based on a thorough understanding of physiology.
The various types of renal tubular acidosis have manifold facets but the basic understanding of their pathophysiology begins with the concept of the “anion gap,” a point of reference that can be used in the differential diagnosis and treatment. In this chapter a number of new causes of type IV renal tubular acidosis—currently considered to be the most common form of renal tubular acidosis—have been pointed out, along with special reference to the mineral, electrolyte, and aldosterone metabolism in the various acidoses and current means of reversing growth failure in the child, especially through bicarbonate treatment.
The mechanism of metabolic acidosis in chronic renal failure, including metabolic acidosis in children undergoing dialysis and in recipients of kidney transplantation, and its relationships to mineral and electrolyte metabolism have been presented.
The pathophysiology of the acidosis related to certain infant formulas and the acidogenic properties of some amino acid solutions employed in total parenteral nutrition have been briefly reviewed.
Finally, the metabolic alkalosis seen in a variety of chloride deficiency syndromes, such as Bartter's syndrome and dietary chloride deprivation, has been discussed and a rational approach to evaluation and treatment outlined.
An appreciation of the physiology of fasting is essential to the understanding of therapeutic dietary interventions and the effect of food deprivation in various diseases. The practice of prolonged fasting for political or religious purposes is increasing, and a physician is likely to encounter such circumstances. Early in fasting weight loss is rapid, averaging 0.9 kg per day during the first week and slowing to 0.3 kg per day by the third week; early rapid weight loss is primarily due to negative sodium balance. Metabolically, early fasting is characterized by a high rate of gluconeogenesis with amino acids as the primary substrates. As fasting continues, progressive ketosis develops due to the mobilization and oxidation of fatty acids. As ketone levels rise they replace glucose as the primary energy source in the central nervous system, thereby decreasing the need for gluconeogenesis and sparing protein catabolism. Several hormonal changes occur during fasting, including a fall in insulin and T(3) levels and a rise in glucagon and reverse T(3) levels. Most studies of fasting have used obese persons and results may not always apply to lean persons. Medical complications seen in fasting include gout and urate nephrolithiasis, postural hypotension and cardiac arrhythmias.
Controversy exists whether protein quantity or quality affect "nitrogen sparing" or physical health while subsisting on very low calorie diets. Therefore, in 38 obese men, nitrogen economy was evaluated over 2 months periods using one of five regimens: 1) 400 kcal high quality protein: 2) 400 kcal low quality protein; 3) 500 kcal 55 g protein natural food; 4) total fasting with potassium; and 5) total fasting without potassium. Up to the 20- and 40-day intervals, mean cumulative nitrogen deficity for all three diet groups was the same but 60% lower than with total fasting. However, within groups, individual capability to conserve nitrogen varied over as much as 2.8-fold. All 10 subjects of diet groups 1 and 2 had negative nitrogen balances to day 21, and six of these subjects were still negative by day 40. The improvement in nitrogen conservation and the ability to attain nitrogen equilibrium was unrelated to the differences in protein quantity and quality. Intake of essential or branched-chain amino acids was also unrelated to the efficiency of nitrogen conservation, as were insulin, glucagon, and 3-hydroxybutyrate levels. The only indicator correlating positively with nitrogen deficit was a fall in complement C3 (r = 0.87). Despite the extent of overall nitrogen loss, no cardiac arrhythmias were observed with either the high or low quality protein diet.
With the conventional method of fasting or aggressive dieting to reduce excess body fat, hunger, weakness, ketogenesis and ketosis are the sequential events that follow. It is not fully understood why, under conditions of negative calorie balance where complete energy release from storage fat is critical, ketosis should arise with a concomitant wastage of energy. Here, I wish to propose a theory that relates the formation of ketone bodies under such conditions to a deficiency in dietary pantothenic acid. Supplementation of this vitamin would facilitate complete catabolism of fatty acids and thus the formation of ketone bodies could be circumvented. As a result, a sufficient amount of energy would be released from storage fat to relieve dieters of the sensation of hunger and weakness which otherwise would be difficult to endure. Hence, using this method for weight reduction together with a careful observation of calorie intake, I have great success in treating overweight-to-obese patients to lose weight.
• The adequacy of pemmican as an emergency ration for short-term survival has been confirmed.
• The isocaloric substitution of pemmican with sugar in amounts over 40 gm was found to have little, if any, effect on fasting blood sugar, nitrogen balance, and ketonuria.
• Evidence is presented that caloric restriction per se and the composition of the diet during caloric restriction have effects which last well beyond the end of the period of dietary stress. Even after an interval of a week of ad libitum dietary intake, these effects may modify responses to a second stress period, manifesting themselves in higher fasting blood sugars, lower nitrogen excretion and a decreased production of ketone bodies.
Three obese females were studied during starvation (0 to 500 Calories per day) and light activity for 18, 28 and 34 days, during which they were given vitamins and liberal amounts of water, and two of them were given electrolytes. Studies were then continued on two subjects given 500 Calorie diets with contained protein.
They experienced little or no hunger, and no untoward effects except halitosis, slight ketonuria and sensitivity to cold. Weight loss amounted to 9.3, 14.1 and 9.5 kg., averaging 810, 330, 250 and 250 grammes per day in successive weeks. This was analysed in terms of its components by the methods usually used in metabolic studies and indirect calorimetry.
Protein catabolism declined as starvation proceeded to a minimum level of 12 to 25 grammes per day. It was decreased by norethandrolone and by carbohydrate feeding. The average daily losses of protein during succeeding weeks were 55, 36, 28 and 18 grammes. Overall, protein accounted for 7.6% to 9.1% of the weight loss and provided 5.0% to 6.9% of the caloric expenditure. Protein lost during starvation ranged from 704 to 1156 grammes, which represent 2.8 to 4.6 kg. of muscle and other cellular tissues. Creatinine excretion gradually fell; it accounted for about 5% of the nitrogen loss initially and 15% in the later stages.
Carbohydrate losses were estimated at 495 to 1050 grammes, accounting for 3.5% to 11.0% of the weight loss and for 3.0% to 6.4% of the Calories. Fat losses amounted to 4.1 to 6.5 kg., being 44% to 68% of the weight loss and providing 87% to 90% of Calories. The average daily loss of fat was 215 grammes. The gaseous exchanges and respiratory quotient fell, and the basal metabolic rate fell more steeply than the body weight or surface area.
Water balance was estimated from measurements and calculations made in two slightly different ways, and the total body water was measured in one subject. All items of losses and gains were determined daily, including metabolic water and evaporation. The cumulative net losses of water reached a peak of 6.2 litres in one subject and were 3.8, 6.0 and 1.2 litres at the end of starvation in the three subjects. The final “corrected” water balances, when allowance was made for the discharge of cell water associated with protein catabolism and for possible initial imbalances, were —1.6, —1.1 and +0.5 litres.
Serum electrolyte levels showed only minor changes. Potassium, sodium and chloride were apparently retained in store in the two subjects who were given these electrolytes. There was a net loss of potassium in all subjects, but in two the potassium balance was normal when account was taken of electrolytes released from cellular breakdown.
Observations from this study and from the literature have been interpreted as emphasizing the idea that ( a ) negative nitrogen balance means the amputation of cells so that cellular water and electrolytes are released in proportion to the protein catabolized, and ( b ) the “desirable” or normal water balance recognizes a constant volume of extracellular fluid plus an intracellular volume which is proportionate to the cellular protein mass. This concept, the nature of obesity tissue, nitrogen metabolism and the possible importance of essential amino acids and of creatinine metabolism are discussed.
The increasing prevalence of obesity has been mirrored by a parallel increase in the number of commercial weight loss programmes. Research evaluating these programmes is meagre, however, compared to the numbers treated. Reluctance of commercial weight loss programmes to meaningfully evaluate their weight loss efficacy may arise from fear that competitors will use the results against them. Evaluation of commercial weight loss programmes usually progresses from testimonials, often by famous people who were successful, to uncontrolled studies of past participants evaluated either by the programme itself or by an outside entity. The gold standard, however, is a scientifically rigorous, controlled study of the programme conducted by an independent entity. Such a study, published in a peer-reviewed journal, can gain credibility for a programme, as it did with Slim Fast, if the results are positive, or herald the end of the programme, as it was with Simeons human chorionic gonadotropin injection clinics. This review of the evolution of the evaluation process of commercial weight loss programmes leads us to conclude that consumers are likely to demand greater scientific rigour in the future, a change that will favour informed choice and discourage the practice of unrealistic advertising that raises false hopes.
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