Several factors relating to superior patient and graft prognosis have proven to be statistically significant. Patients who have been admitted for transplant directly from home rather than the hospital, younger patients over one year of age, those receiving their first transplant, those receiving transplants at experienced transplant centers, and who receive antibody or sirolimus-based induction therapies have increased rates of survival. [ 9 ] [ 15 ]  Furthermore, underlying  etiology , [ 29 ]  the presence of  comorbidity , the frequency of previous surgery, nutritional status, and the level of liver function have been found to affect patient-graft survival . [ 30 ]  Patients with a pre-transplant diagnosis of volvulus were found to possess a lower risk of mortality. [ 29 ]  As of 2008, the longest recorded surviving transplant survived for 18 years. [ 14 ]  Between 1999 and 2008, 131 retransplant procedures were performed in the United States. [ 7 ]


The improvement to quality of life following an intestinal transplantation is significant. Of living patients 6 months after transplant, 70% are considered to have regained full intestinal function, 15% are at partial function, and 15% have had their grafts removed. [ 9 ] [ 14 ]  For those with full function, enteral nutritional  autonomy  is high. [ 7 ]  The ability to resume regular activities such as the ability to consume food and exert control over digestive function is certainly a welcome return for patients. The low quality of life induced by intestinal failure is oftentimes further supplemented by significant  psychosocial   disability  and  narcotic   dependence . Following transplantation, these have been found to generally decrease. [ 15 ]  According to surveys comparing patients who have undergone transplants and those that have not, there seems to be a remarkable improvement for transplant recipients in such areas as  anxiety , depression,  appearance ,  stress ,  parenting ,  impulsiveness ,  optimism ,  medical compliance , and the quality of  relationships . [ 14 ] [ 15 ] [ 31 ]


Receiving an organ transplant of any kind is a highly significant investment financially, but a successful, well-functioning transplant can be very  cost-efficient  relative to alternate therapies. Total charges to maintain PN at home can reach upwards of $150,000 a year, even though the actual cost of nutrition is typically only $18 to $22 a day. [ 5 ] [ 14 ]  This excludes the cost for additional home support, equipment, and the care of PN-related complications. The cost involved in undergoing intestinal transplantation, including the initial hospitalization for the transplant, can range from $150,000 to $400,000, and reoccurring hospitalizations are common up through the second year. Two to three years post-transplant, the financial cost of transplantation reaches parity with PN and is more cost-effective thereafter. [ 11 ] [ 14 ]


2PMV ,  3KQ4


Intrinsic factor  ( IF ),  cobalamin binding intrinsic factor , [ 5 ]  also known as  gastric intrinsic factor  ( GIF ), is a  glycoprotein  produced by the  parietal cells  (in humans) or chief cells (in rodents) of the  stomach . It is necessary for the absorption of  vitamin B 12  later on in the distal  ileum  of the  small intestine . [ 6 ]  In humans, the gastric intrinsic factor  protein  is encoded by the  CBLIF   gene . [ 5 ]   Haptocorrin  ( transcobalamin I ) is another glycoprotein secreted by the  salivary glands  which binds to  vitamin B 12 . Vitamin B 12  is acid-sensitive and in binding to haptocorrin it can safely pass through the acidic stomach to the duodenum. [ 7 ]


In the less acidic environment of the  small intestine , pancreatic enzymes digest the glycoprotein carrier and vitamin B 12  can then bind to intrinsic factor. [ 7 ]  This new complex is then absorbed by the epithelial cells ( enterocytes ) of the  ileum . [ 7 ]  Inside the cells, vitamin B 12  dissociates once again and binds to another protein,  transcobalamin II ; the new complex can then exit the epithelial cells to be carried to the liver. [ 8 ]


Intrinsic factor is secreted by  parietal cells  within the stomach, and so is present in the gastric juice as well as in the  gastric mucous membrane . [ 9 ]  The optimum pH for its action is approximately 7. [ 10 ]  Its concentration does not correlate with the amount of  HCl  or  pepsin  in the gastric juice, e.g., intrinsic factor may be present even when pepsin is largely absent. [ 11 ]  The site of formation of the intrinsic factor varies in different species. In pigs it is obtained from the  pylorus  and beginning of the  duodenum ; [ 12 ]   in human beings it is present in the  fundus  and body of the  stomach . [ 13 ]


The limited amount of normal human gastric intrinsic factor limits normal efficient absorption of B 12  to about 2 μg per meal, a nominally adequate intake of B 12 . [ 14 ]


In  pernicious anemia , which is usually an  autoimmune disease ,  autoantibodies  directed against intrinsic factor or parietal cells themselves lead to an intrinsic factor deficiency,  malabsorption  of vitamin B 12 , and subsequent  megaloblastic anemia . [ 15 ]   Atrophic gastritis  can also cause intrinsic factor deficiency and anemia through damage to the parietal cells of the stomach wall. [ 16 ]   Pancreatic exocrine insufficiency  can interfere with normal dissociation of vitamin B 12  from its binding proteins in the small intestine, preventing its absorption via the intrinsic factor complex. [ 17 ]  Other risk factors contributing to pernicious anemia are anything that damages or removes a portion of the stomach's parietal cells, including  bariatric surgery , gastric tumors, gastric ulcers, and excessive consumption of alcohol. [ citation needed ]


Mutations in the  GIF  gene are responsible for a rare inheritable disease called  intrinsic factor deficiency [ 18 ]  which results in malabsorption of vitamin B 12 . [ 19 ]


In most countries,  intramuscular injections  of vitamin B 12  are used to treat  pernicious anemia . [ 20 ]  Orally administered vitamin B 12  is absorbed without intrinsic factor, but at levels of less than one percent than if intrinsic factor is present. [ 21 ]   Despite the low amounts absorbed, oral vitamin B 12  therapy is effective at reducing symptoms of pernicious anemia. [ 22 ]


Vitamin B 12  can also be given  sublingually , but there is no evidence that this route of administration is superior to the oral route, [ 23 ]  and only Canada and Sweden routinely prescribe this route of administration. [ 20 ]


Because vitamin B 12  absorption is a multistep process that involves the stomach, pancreas and small intestine, and is mediated by two carriers:  Haptocorrin  and intrinsic factor, and because  Haptocorrin  ( transcobalamin I ) binds to vitamin B 12 , and  Vitamin B 12  is acid-sensitive, when vitamin B 12  binds to  Haptocorrin  it can safely pass through the acidic stomach to the duodenum, given time in the mouth. [ 7 ]


Divisions


John Harvey Kellogg  (February 26, 1852 – December 14, 1943) was an American businessman,  inventor , physician, [ 1 ]  and advocate of the  Progressive Movement . [ 2 ]  He was the director of the  Battle Creek Sanitarium  in  Battle Creek, Michigan , founded by members of the  Seventh-day Adventist Church . It combined aspects of a European spa, a  hydrotherapy  institution, a hospital and high-class hotel. Kellogg treated the rich and famous, as well as the poor who could not afford other hospitals. According to  Encyclopædia Britannica , his "development of dry breakfast cereals was largely responsible for the creation of the  flaked-cereal industry , with the founding and the culmination of the global conglomeration brand of  Kellogg's (now Kellanova) ." [ 1 ]


An early proponent of the  germ theory of disease , Kellogg was well ahead of his time in relating  intestinal flora  and the presence of bacteria in the intestines to health and disease. The sanitarium approached treatment in a  holistic  manner, actively promoting vegetarianism, nutrition, the use of yogurt  enemas  to clear "intestinal flora", exercise, sun-bathing, and  hydrotherapy , as well as abstinence from smoking tobacco, drinking alcoholic beverages, and sexual activity. Kellogg dedicated the last 30 years of his life to promoting  eugenics  and  segregation . [ 3 ]  Kellogg was a major leader in progressive health reform, particularly in the second phase of the  clean living movement . [ 4 ] [ 5 ]  He wrote extensively on science and health. His approach to "biologic living" combined scientific knowledge with Adventist beliefs, promoting health reform, and  temperance . [ 6 ]  Many of the vegetarian foods that Kellogg developed and offered his patients were publicly marketed: Kellogg's brother,  Will Keith Kellogg , is best known today for the invention of the  breakfast cereal   corn flakes . [ 7 ] [ 8 ]


Kellogg held  liberal theological beliefs  radically different from mainstream  Nicene Christianity  and emphasized what he saw as the importance of  human reason  over many aspects of  traditional doctrinal authority . He strongly rejected  fundamentalist  and  conservative  notions of  original sin ,  human depravity , and  the atonement of Jesus , viewing the last in terms of "his exemplary life" on Earth rather than  death . [ 2 ] [ 9 ]  Becoming a  Seventh-day Adventist  as their beliefs shifted towards  Trinitarianism  during the 1890s, Adventists were "unable to accommodate the essentially  liberal  understanding of Christianity" exhibited by Kellogg, viewing his theology as  pantheistic  and unorthodox. [ 2 ] [ 9 ]  Disagreements with other members of the SDA led to a major schism: he was  disfellowshipped  in 1907, but continued to follow many of their beliefs and directed the sanitarium until his death. Kellogg helped to establish the  American Medical Missionary College  in 1895. [ 10 ]   Popular misconceptions  have wrongly attributed various cultural practices, inventions, and historical events to Kellogg. [ 11 ] [ 12 ]


John Harvey Kellogg was born in  Tyrone, Michigan , on February 26, 1852, [ 13 ]  to John Preston Kellogg (1806–1881) and his second wife Ann Janette Stanley (1824–1893). [ 7 ]  His father, John Preston Kellogg, was born in  Hadley, Massachusetts ; his ancestry can be traced back to the founding of Hadley, Massachusetts, where a great-grandfather operated a ferry. [ 14 ]
John Preston Kellogg and his family moved to Michigan in 1834, and after his first wife's death and his remarriage in 1842, to a farm in Tyrone Township. [ 15 ] : 9  [ 16 ] : 14–18
In addition to six children from his first marriage, John Preston Kellogg had 11 children with his second wife Ann, including John Harvey and his younger brother,  Will Keith Kellogg . [ 17 ]


John Preston Kellogg became a member of several  revivalist  movements, including the  Baptists , the  Congregationalist Church , and finally the  Seventh-day Adventist Church . [ 15 ] : 9   He was one of four adherents who pledged substantial sums to convince Seventh-day Adventists  Ellen G. White  and her husband  James Springer White  to relocate to  Battle Creek, Michigan , with their publishing business, in 1855. [ 15 ] : 10   He persuaded a Seventh-day Adventist couple,  Daniel H. Kress  and  Lauretta E. Kress , to become doctors at Michigan where he had studied; they were early founders of what became  Washington Adventist Hospital . In 1856, the Kellogg family moved to Battle Creek to be near other members of the denomination. There John Preston Kellogg established a  broom  factory. [ 15 ] : 9   The Kelloggs believed that the  Second Coming  of Christ was imminent, and that formal education of their children was therefore unnecessary. Originally a sickly child, John Harvey Kellogg attended Battle Creek public schools only briefly, from ages 9–11. He left school to work sorting brooms in his father's broom factory. Nonetheless, he read voraciously and acquired a broad but largely self-taught education. At age 12, John Harvey Kellogg was offered work by the Whites. He became one of their protégés, [ 18 ] : 111–112   rising from errand boy to  printer's devil , and eventually doing proofreading and editorial work. [ 19 ]  He helped to set articles for  Health, or how to live  and  The Health Reformer , becoming familiar with Ellen G. White's theories of health, and beginning to follow recommendations such as a vegetarian diet. [ 16 ] : 28   Ellen White described her husband's relationship with John Harvey Kellogg as closer than that with his own children. [ 18 ] : 111–112


Kellogg hoped to become a teacher, and at age 16 taught a district school in Hastings, Michigan. [ 16 ] : 29–30   By age 20, he had enrolled in a teacher's training course offered by  Michigan State Normal School . [ 20 ]  The Kelloggs and the Whites, however, convinced him to join his half-brother Merritt,  Edson White ,  William C. White , and Jennie Trembley, as students in a six-month medical course at Russell Trall's  Hygieo-Therapeutic College  in  Florence Township, New Jersey . Their goal was to develop a group of trained doctors for the Adventist-inspired Western Health Reform Institute in Battle Creek. [ 16 ] : 30   Under the Whites' patronage, John Harvey Kellogg went on to attend medical school at the  University of Michigan  and the  Bellevue Hospital Medical College  in New York City. He graduated in 1875 with a medical degree. [ 20 ]  In October 1876, Kellogg became director of the Western Health Reform Institute. [ 20 ]  In 1877, he renamed it the  Battle Creek Medical Surgical Sanitarium , [ 8 ]  cleverly coining the term "sanitarium" to suggest both hospital care and the importance of sanitation and personal health. [ 21 ]
Kellogg would lead the institution until his death in 1943. [ 8 ]


Kellogg was brought up in the  Seventh-day Adventist Church  from childhood. Selected as a protégé of the Whites and trained as a doctor, Kellogg held a prominent role as a speaker at church meetings. [ 15 ] : xiii–xv   Throughout his lifetime, Kellogg experienced pressure from both science and religion regarding his theological views. [ 15 ] : xiii–xv


At the Seventeenth Annual Session of the General Conference of Seventh-day Adventists, October 4, 1878, the following action was taken:


WHEREAS, The impression has gone out from some unknown cause that J. H. Kellogg, M.D., holds infidel sentiments, which does him great injustice, and also endangers his influence as physician-in-chief of the Sanitarium; therefore

RESOLVED, That in our opinion justice to the doctor and the Institute under his medical charge, demand that he should have the privilege of making his sentiments known, and that he be invited to address those assembled on this ground, upon the harmony of science and the Sacred Scriptures.

This resolution was unanimously adopted, after which the Conference adjourned to the call of the chair.


[Note. – In accordance with the foregoing resolution, Dr. Kellogg gave, before a large audience, October 6, an able address on the harmony of science and the Bible, for which the congregation tendered him a vote of thanks.] [ 22 ]


Kellogg rejected  Christian fundamentalism  and promoted the tenets of theological modernism. He rejected many of the traditional tenets of  Nicene Christianity , viewing the  atonement of Jesus  as "his exemplary life" on Earth rather than the Cross. [ 2 ]  Kellogg mocked the concepts of  original sin  and  inherent human depravity , frequently joking that "the total depravity which we often hear talked about is, half the time at least, nothing more nor less than total indigestion". [ 2 ]  Historian Brian C. Wilson writes: [ 2 ]


One of the most controversial aspects of Kellogg's developing theology... was its decidedly non-Christocentric focus. While "God" is mentioned one hundred times, "Jesus Christ" is mentioned only briefly, twelve times, and is treated as something of a peripheral character.


Kellogg defended "the harmony of science and the Bible" throughout his career, but he was active at a transitional time, when both science and medicine were becoming increasingly  secularized . White and others in the Adventist ministry worried that Kellogg's students and staff were in danger of losing their religious beliefs, while Kellogg felt that many ministers failed to recognize his expertise and the importance of his medical work. There were ongoing tensions between his authority as a doctor, and their authority as ministers. [ 23 ]
Nonetheless, Kellogg attempted to reconcile science and medicine with religion, rejecting their separation, and emphasizing the presence of God within God's creation of living things. [ 15 ] : xiii–xv


The heart is a muscle. The heart beats. My arm will contract and cause the fist to beat; but it beats only when my will commands. But here is a muscle in the body that beats when I am asleep. It beats when my will is inactive and I am utterly unconscious. It keeps on beating all the time. What will is it that causes this heart to beat? The heart can not beat once without a command. To me it is a most wonderful thing that a man's heart goes on beating. It does not beat by means of my will; for I can not stop the heart's beating, or make it beat faster or slower by commanding it by my will. But there is a will that controls the heart. It is the divine will that causes it to beat, and in the beating of that heart that you can feel, as you put your hand upon the breast, or as you put your finger against the pulse, an evidence of the divine presence that we have within us, that God is within, that there is an intelligence, a power, a will within, that is commanding the functions of our bodies and controlling them… [ 24 ]


He further elaborated these ideas in his book  The Living Temple  (1903):


There is a clear, complete, satisfactory explanation of the most subtle, the most marvelous phenomena of nature, – namely, an infinite Intelligence working out its purposes. God is the explanation of nature, – not a God outside of nature, but in nature, manifesting himself through and in all the objects, movements, and varied phenomena of the universe. ... The tree does not create itself; a creative power is constantly going forward in it. Buds and leaves come forth from within the tree ... So there is present in the tree a power which creates and maintains it, a tree-maker in the tree, a flower-maker in the flower, – a divine architect who understands every law of proportion, an infinite artist who possesses a limitless power of expression in color and form; there is, in all the world about us, an infinite, divine, though invisible Presence, to which the unenlightened may be blind, but which is ever declaring itself by its ceaseless, beneficent activity. [ 25 ]


At the same time that Kellogg defended the presence of God in nature against  secularization , his co-religionists saw his descriptions of the presence of God in nature as evidence of
 panentheistic  tendencies (Everything is in God). [ 26 ]
Kellogg rejected their religious criticisms, asserting that his views on indwelling divinity were simply a restatement of the omnipresence of God, and not pantheism. [ 15 ] : xiii–xv  [ 16 ] : 189


His theological views went against many of the traditional tenets of  Nicene Christianity . As  Seventh-day Adventist  beliefs shifted towards orthodox Trinitarianism during the 1890s, Adventists within the denominations were "unable to accommodate the essentially  liberal  understanding of Christianity" exhibited by Kellogg, viewing his theology as  pantheistic  and unorthodox. [ 9 ]  What came to be referred to as the "Pantheism Crisis" of 1903 was a pivotal moment in the church's history. Kellogg's theological views were only one of the issues involved: operation of the sanitarium was equally if not more important. [ 15 ] : xiii–xv
Control of the sanitarium and its finances had been a source of contention for some time, especially as the institution expanded and attracted more affluent patients. [ 27 ]
Tensions came to a head when the Battle Creek Sanitarium, originally owned by the Seventh-day Adventist Church but run by Kellogg, was destroyed by fire on February 18, 1902. Although almost all of the guests escaped safely, property loss was estimated at $300,000 to $400,000, about twice the insured value. [ 28 ]


Ellen G. White , who had proclaimed that a cleansing sword of fire was poised over the increasingly "worldly" and business-oriented Battle Creek, was against rebuilding the large institution. [ 29 ] [ 30 ]  Although she apparently wrote a manuscript testifying against the rebuilding in 1902, it was not sent to Kellogg at that time, [ 29 ]  and Kellogg did not directly consult her about his plans. [ 23 ] : 38   With support of the board of directors, he not only rebuilt the institution, but doubled its size. The new building was designed by architect  Frank Mills Andrews  of Ohio [ 31 ]  and opened on May 31, 1903. [ 15 ] : xiii–xv  [ 26 ] : 189   Designed to be fireproof, the new brick building was six stories high, with an elegant frontage extending 550 feet along Washington Avenue, and three wings opening out behind. It included, among other things, a solarium and palm court, and it cost more than $700,000. [ 32 ]


Kellogg used proceeds from his book  The Living Temple  to help pay the costs of reconstruction. The book's printing was opposed by a commission of the General Council of the Adventists after  W. W. Prescott , one of the four members of the commission, argued that it was heretical. When Kellogg arranged to print it privately, the book went through its own trial by fire: on December 30, 1902, fire struck the  Herald  where the book was typeset and ready to print. [ 26 ]  When it finally appeared in 1903, the book was sharply criticized by White for what she considered its many statements of pantheism. [ 15 ] : 84–89   Over the next few years, there was increasing conflict between Kellogg, General Conference President  A. G. Daniells  and others. [ 29 ]  In 1907, Kellogg was "disfellowshipped", as part of a schism that split the church. Kellogg retained control of the Battle Creek Sanitarium and the American Medical Missionary College, and continued to promote Adventist ideas of health and well-being at those institutions. [ 23 ] [ 33 ]


In later life, Kellogg spoke positively of Seventh-day Adventists and Ellen G. White's prophetic ministry, despite their struggles. In 1941, in response to critic E. S. Ballenger, Kellogg admonished Ballenger for his critical attitude to Mrs. White. [ 34 ]


Mrs. White was unquestionably an inspired woman. In spite of this fact, she was human and made many mistakes and probably suffered more from those mistakes than any person ever did. Nevertheless, I knew the woman was sincere and honest and that the influence of her life was immensely helpful to a vast multitude of people, and I have not the slightest desire in any way to weaken in the smallest degree the good influence of her life and work. [ 34 ]


Kellogg was a  Seventh-day Adventist  until mid-life, and gained fame while being the chief medical officer of the Battle Creek Sanitarium, which was owned and operated by the Seventh-day Adventist Church. The sanitarium was operated based on the church's health principles. Adventists believe in promoting a vegetarian diet, abstinence from alcohol and tobacco, and a regimen of exercise, all of which Kellogg followed. He is remembered as an advocate of vegetarianism [ 35 ]  and wrote in favor of it, even after leaving the Adventist Church. [ 36 ]  His dietary advice in the late 19th century discouraged meat-eating, but not emphatically so. His development of a bland diet was driven in part by the Adventist goal of reducing sexual stimulation. [ 37 ] [ failed verification ]


Kellogg was an especially strong proponent of  nuts , which he believed would save humanity in the face of decreasing food supplies. [ 38 ]  Though mainly renowned nowadays for his development of  corn flakes , Kellogg also invented a process for making  peanut butter [ 39 ] [ 40 ]  and developed healthy "granose biscuits" which became popular as far away as Australia [ 41 ]  and England. [ 42 ]


The Battle Creek Sanitarium had its own experimental kitchen. There, Ella Eaton Kellogg helped to develop vegetarian foods, and supervised a "school of cookery" which taught classes in food preparation for homemakers. [ 43 ]  She published a cookbook,  Science in the Kitchen , containing hundreds of recipes along with discussions of nutrition and household and diet management. Some of its inventive vegetarian recipes use food products created at the sanitarium, such as Nuttolene (a meat pâté made from peanuts), [ 42 ]
Protose (a combination of nuts and grains), [ 8 ]  and various types of nut butters. [ 40 ] [ 44 ]


Kellogg believed that most disease is alleviated by a change in  intestinal flora . He posited that bacteria in the intestines can either help or hinder the body; that pathogenic bacteria produce  toxins  during the digestion of protein which poison the blood; that a poor diet favors harmful bacteria that can then infect other tissues in the body; that the intestinal flora is changed by diet and is generally changed for the better by a well-balanced vegetarian diet favoring low- protein ,  laxative , and high- fiber  foods. He recommended various regimens of specific foods designed to heal particular ailments.


Kellogg further believed that natural changes in intestinal flora could be sped by enemas seeded with favorable bacteria. He advocated the frequent use of an enema machine to cleanse the bowel with several gallons of water. Water enemas were followed by the administration of a pint of  yogurt  – half was eaten, the other half was administered by enema, "thus planting the protective germs where they are most needed and may render most effective service." The yogurt served to replace the intestinal flora of the bowel, creating what Kellogg claimed was a squeaky-clean  intestine . [ 45 ]


Sanitarium visitors also engaged in breathing exercises and mealtime marches, to promote proper  digestion  of food throughout the day. Because Kellogg was a staunch supporter of  phototherapy , the sanitarium made use of artificial  sunbaths . [ 8 ]  Kellogg was a skilled surgeon, who often donated his services to indigent patients at his clinic. [ 46 ]


He had many notable patients, such as former president  William Howard Taft , composer and pianist  Percy Grainger , arctic explorers  Vilhjalmur Stefansson  and  Roald Amundsen , world travellers  Richard Halliburton  and  Lowell Thomas , aviator  Amelia Earhart , economist  Irving Fisher , Nobel prize winning playwright  George Bernard Shaw , actor and athlete  Johnny Weissmuller , founder of the Ford Motor Company  Henry Ford , inventor  Thomas Edison , [ 47 ]  African-American activist  Sojourner Truth , and actress  Sarah Bernhardt . [ 48 ] [ 49 ] [ 50 ]


John Harvey Kellogg developed and marketed a wide variety of vegetarian foods. Many of them were meant to be suitable for an invalid diet, and were intentionally made easy to chew and to digest. Starchy foods such as grains were ground and baked, to promote the conversion of  starch  into  dextrin . Nuts were ground and boiled or steamed. [ 16 ] : 114–115, 119


The foods Kellogg developed also tended to be bland. In this, Kellogg followed the teachings of  Ellen G. White  and  Sylvester Graham  who recommended a diet of bland foods to minimize excitement, sexual arousal, and masturbation. [ 51 ]


Around 1877, John H. Kellogg began experimenting to produce a softer breakfast food, something easy to chew. He developed a dough that was a mixture of wheat,  oats , and corn. It was baked at high temperatures for a long period of time, to break down or "dextrinize" starch molecules in the grain. After it cooled, Kellogg broke the bread into crumbs. The cereal was originally marketed under the name " Granula " but this led to legal problems with  James Caleb Jackson  who already sold a wheat cereal under that name. In 1881, under threat of a lawsuit by Jackson, Kellogg changed the sanitarium cereal's name to "Granola". [ 52 ]
It was used initially by patients at the sanitarium, but slowly began to build up a following among former patients. [ 16 ] : 115   In 1890, John formed the Sanitas Food Company to develop and market food products. [ 4 ] : 53


The Kelloggs are best known for the invention of the famous breakfast cereal  corn flakes . The development of the flaked cereal in 1894 has been variously described by those involved: Ella Eaton Kellogg, John Harvey Kellogg, his younger brother Will Keith Kellogg, and other family members. There is considerable disagreement over who was involved in the discovery, and the role that they played. According to some accounts, Ella suggested rolling out the dough into thin sheets, and John developed a set of rollers for the purpose. According to others, John had the idea in a dream, and used equipment in his wife's kitchen to do the rolling. It is generally agreed that upon being called out one night, John Kellogg left a batch of wheat-berry dough behind. Rather than throwing it out the next morning, he sent it through the rollers and was surprised to obtain delicate flakes, which could then be baked. Will Kellogg was tasked with figuring out what had happened, and recreating the process reliably. Ella and Will were often at odds, and their versions of the story tend to minimize or deny each other's involvement, while emphasizing their own part in the discovery. [ 52 ]  The process that Kellogg had discovered, tempering, was to be a fundamental technique of the flaked cereal industry. [ 16 ] : 116


A patent for "Flaked Cereals and Process of Preparing Same" was filed on May 31, 1895, and issued on April 14, 1896, to John Harvey Kellogg as Patent No. 558,393. Significantly, the patent applied to a variety of types of grains, not just to wheat. John Harvey Kellogg was the only person named on the patent. [ 53 ]  Will later insisted that he, not Ella, had worked with John, and repeatedly asserted that he should have received more credit than he was given for the discovery of the flaked cereal. [ 52 ]


During their first year of production, the Kelloggs sold tens of thousands of pounds of flaked cereal, marketing it as "Granose". They continued to experiment using rice and corn as well as wheat, and in 1898 released the first batch of Sanitas Toasted Corn Flakes. A modified version with a longer shelf life was released in 1902. [ 8 ]  By that time, both "Granose Biscuits" and "Granose Flakes" were available. [ 54 ]


Will Kellogg continued to develop and market flaked cereal. When he proposed adding sugar to the flakes, John would not agree to the change.
So, in 1906, Will started his own company, the Battle Creek Toasted Corn Flake Company. This marked the start of a decades-long feud between the brothers. Will's Battle Creek Toasted Corn Flake Company eventually became the  Kellogg Company , while John was denied the right to use the Kellogg name for his cereals. [ 8 ] [ 4 ] : 53  [ 55 ]


They had other competitors as well, including  C. W. Post . Post was treated at the Battle Creek Sanitarium between February 6 and November 9, 1891, and later by  Christian Scientists  whom he credited with his successful treatment. He settled in Battle Creek, opened his own sanitarium, the LaVita Inn, in March 1892, and founded his own dry foods company,  Post Holdings . [ 56 ]
Post started selling  Postum  coffee substitute in 1895. [ 57 ]
He issued  Grape-Nuts  breakfast cereal, a mixture of yeast, barley and wheat, in January 1898. [ 56 ]
In January 1906, Post introduced "Elijah's Manna", later renaming it  Post Toasties  Double-Crisp Corn Flakes, and marketing it as a direct competitor to Kellogg's Corn Flakes. [ 55 ] [ 58 ]


John Harvey Kellogg was inducted into the  National Inventors Hall of Fame  in 2006 for the discovery of tempering and the invention of the first dry flaked breakfast cereal, which "transformed the typical American breakfast". [ 59 ]


John H. Kellogg is one of several people who have been credited with the invention of peanut butter. [ 60 ] [ 39 ]
Rose Davis of  Alligerville, New York  has been reported to have made a peanut spread as early as 1840, after her son described Cuban women grinding peanuts and eating the paste on bread. [ 39 ] : 30
In 1884,  Marcellus Gilmore Edson  (1849–1940) of  Montreal , Canada obtained a patent for the "Manufacture of peanut-candy", combining 1 part of a "flavoring paste" made from roasted peanuts with 7 parts of sugar. [ 61 ]
By 1894, George A. Bayle of St. Louis was selling a "Cheese Nut" snack food containing peanuts and cheese; a peanut-only version was apparently more successful. [ 60 ] [ 62 ]
 George Washington Carver  is often credited because of his scientific work with peanuts and promotion of their use. [ 63 ] : 357   Carver and Kellogg corresponded in the 1920s and 30s about the use of both peanuts and  sweet potatoes . [ 64 ]


Some form of nut butter, likely made with peanuts, was served to patients at the Battle Creek Sanitarium before October 1895, when Kellogg wrote to Ellen White that "some very excellent preparations from nuts" had entirely replaced butter. [ 63 ] : 357
Kellogg did not patent peanut butter explicitly, and later stated that this was intentional: "Let everybody that wants it have it, and make the best use of it". [ 39 ] : 32   Kellogg did, however, apply for two patents relating to "nut butters" in 1895, before anyone else did so. [ 63 ]


On November 4, 1895, John H. Kellogg applied for two patents that are relevant to the production of peanut butter. [ 63 ]  Patent No. 567901, granted September 15, 1896, was for a "Food Compound" which produced "an improved article of manufacture, the alimentary product composed of completely digested starch, completely-emulsified vegetable oil such as described, and thoroughly cooked and finely-divided vegetable proteins derived from nuts, as specified."
The process described involved taking raw edible nuts, preferably peanuts or almonds, blanching them to remove their skins, and then boiling them for several hours. The nuts were then crushed and passed through rollers to separate out "a fine and comparatively dry and nearly white nutmeal" and a "moist, pasty, adhesive, and brown" butter or paste. [ 65 ]


The second patent, No. 604493, granted on May 24, 1898, was for a "Process of Producing Alimentary Products" from "edible nuts, preferably peanuts". The process for making the paste again involved boiling the peanuts, but noted that roasting was a possible alternative. The final substance was heated in sealed cans to obtain "a product differing in many ways from the original paste" with a consistency resembling cheese. [ 66 ]


By 1898, the Kelloggs were marketing a wide variety of nut-based foods through the Sanitas Nut Food Company. [ 67 ]
Kellogg marketed nut butters as a nutritious protein substitute for people who had difficulty chewing on solid food. Because peanuts were the least expensive nut available, they rapidly dominated the nut butter market. [ 63 ]
 [ 39 ] [ 40 ]


Joseph Lambert, who had worked for Kellogg at the sanitarium, began selling a hand-operated peanut butter grinder in 1896. [ 68 ]  In 1899, his wife Almeida Lambert published a  Guide for Nut Cookery . [ 39 ] : 33


Kellogg credited his interest in  meat substitutes  to  Charles William Dabney , an agricultural chemist and the Assistant Secretary of Agriculture. Dabney wrote to Kellogg on the subject around 1895. [ 16 ] : 119


In 1896, Kellogg introduced but did not patent "Nuttose", the first commercially produced alternative to meat. Nuttose was made primarily from peanuts and resembled "cold roast  mutton ". [ 42 ] : 6
By seasoning or marinating, Nuttose could be made to taste like fried chicken or barbeque. Served with mashed potatoes and vegetables, it could mimic a traditional American meal. [ 69 ]


On March 19, 1901, Kellogg was granted the first United States Patent for a "vegetable substitute for meat", for a blend of nuts and grain cereals called "Protose".
In applying for  US patent 670283A , John Harvey Kellogg, "Vegetable-food Compound", issued June 8, 1899   , Kellogg described Protose as a product "which shall possess equal or greater nutritive value in equal or more available form... By proper regulation of the temperature and proportions of the ingredients, various meat-like flavors are developed, which give the finished product very characteristic properties." [ 42 ] : 6  [ 70 ]
Nuttose and Protose were the first of many meat alternatives. [ 69 ]


In addition to developing  imitation meats  variously made from nuts, grains, and soy, Kellogg also developed the first  acidophilus   soy milk , [ 71 ]  which was patented in 1934. [ 72 ]
Kellogg advocated that it be administered to bottle-fed babies, to improve their intestinal fauna and combat bowel infections. Perhaps his most famous patients were the  Dionne quintuplets . When he learned that Marie had a bowel infection, Kellogg sent a case of his soy acidophilus to their doctor,  Allan Roy Dafoe . When Marie's infection cleared up, Dafoe requested that Kellogg send an ongoing supply for the quintuplets. By 1937, each one consumed at least a pint per day. Another famous patient who benefited from soy acidophilus was polar explorer  Richard E. Byrd . [ 52 ] : 330–333
Kellogg also sold yogurt, soy flour, and soy bread. [ 71 ]


Although they are less discussed than his food creations, Kellogg designed and improved upon a number of medical devices that were regularly used at the Battle Creek Sanitarium in surgical operations and in treatment modalities falling under the term " physiotherapy ".
Many of the machines invented by Kellogg were manufactured by the Battle Creek Sanitarium Equipment Company, which was established in 1890. [ 32 ]
Dr. Kellogg attempted to popularize these treatment methods, including  electrotherapy ,  hydrotherapy , and motor therapy, in his work  The Home Handbook of Domestic Hygiene and Rational Medicine , first published in 1881. [ 73 ]


As he specialized in certain gynecological surgeries (particularly  hemorrhoidectomies  and  ovariotomies ) and  gastrointestinal  surgeries, he developed various instruments for these operations. These included specialized hooks and  retractors , a heated operating table, and an aseptic drainage tube used in abdominal surgery. [ 16 ] : 116–127


Additionally, Kellogg took keen interest in devising instruments for  light therapy , mechanical exercising, proper breathing, and  hydrotherapy . His medical inventions spanned a wide range of applications and included a hot air bath, vibrating chair, oscillomanipulator, window tent for fresh air,  pneumograph  to graphically represent respiratory habits, [ 16 ]   loofah  mitt, and an apparatus for home sterilization of milk. [ 16 ]  Some of his inventions were fashionable enough to be included in the first class gymnasium of the  RMS Titanic . [ 74 ]


Kellogg did not make concerted efforts to profit from his medical inventions. Kellogg's statement in 1916 about his food company sheds light on his general motivations: "I desire to make clear...that the food business I have been carrying on is a part of my general scheme to propagate the ideas of health and biological living. Otherwise, I should not have engaged in it as a commercial enterprise, but I have carried it on as a part of the general philanthropic work in which I was engaged." [ 16 ]


Partly motivated by the overcast skies of Michigan winters, Kellogg experimented with and worked to develop light therapies, as he believed in the value of the  electric light bulb  to provide heat penetration for treating bodily disorders. [ 16 ]


He constructed his first incandescent light bath in 1891, claiming to treat thousands of patients at the Battle Creek Sanitarium before exhibiting the bath at the  World's Columbian Exposition  in Chicago in 1893. [ 75 ]  The invention reportedly aroused little attention there but was brought back to Germany, where it began to be manufactured and sold. [ 75 ]  It was spread to Vienna by Kellogg's friend Dr.  Wilhelm Winternitz ; installed in royal palaces across Europe; and popularly replaced old Turkish steam baths at athletic clubs. [ 16 ]  Only after cabinet baths became popular in Europe did demand within the United States develop. It was imported from  Berlin  to New York "as a therapeutic novelty". [ 75 ]  In 1896, Kellogg patented the radiant-heat bath in the United States (US558394).


In order "to make a record of his work and experience as a pioneer in this branch of physiotherapeutics", Kellogg published his book  Light Therapeutics: a practical manual of phototherapy for the student and the practitioner, with special reference to the incandescent electric-light bath  in 1910. [ 76 ]  In the short work, Kellogg describes the application of the arc light to the spine, chest, abdominal region, loins, shoulders, hip and thigh, knees and other joints. He also goes into detail about combining electrotherapies with hydrotherapies, e.g. the electric light bath with shower and shampoo. [ 77 ]


Though Kellogg stated that "electricity is not capable of accomplishing half the marvels that are claimed for it by many enthusiastic electrotherapists," he still believed electric currents to be "an extremely valuable therapeutic agent, especially when utilized in connection with hydrotherapy, thermotherapy, and other physiologic methods." [ 78 ]  As a result, electrotherapy coils were used in the Static Electrical Department of the Battle Creek Sanitarium especially for cases of paresthesias of neurasthenia, insomnia, and certain forms of neuralgia. [ 78 ]  Devices were also used to administer electric shocks to various parts of a patient's body.


Vibrational therapy by way of sinusoidal (high-frequency oscillating) electric current was discovered by Kellogg in 1884 to have medical use for increasing blood circulation and passive exercise. [ 16 ]  In particular, Kellogg invented a vibrating chair used to stimulate vital organs in the lower abdomen. [ 16 ]  Even today one can visit the Kellogg Discovery Center in Battle Creek, Michigan, and sit on Kellogg's vibrating chair, which is equipped to mechanically oscillate 20 times per second. [ 79 ]  Furthermore, Kellogg devised an electrotherapy exercise bed in which a sinusoidal current that produced muscular contraction could be delivered without pain for twenty minutes and reportedly achieve the stimulation of a brisk four-mile walk. [ 16 ]


Massage devices included two- or four-person foot vibrators, a mechanical slapping massage device, and a kneading apparatus that was advertised in 1909 to sell for  $150.00  (equivalent to about $5,100 in 2023). [ 80 ]  Kellogg advocated mechanical massage, a branch of  mechanotherapy , for cases of  anemia , general debility, and muscular or nervous weakness. [ 81 ]


In 1936, Kellogg filed a petition for his invention of improvements to an "irrigating apparatus particularly adaptable for colonic irrigating, but susceptible of use for other irrigation treatments." [ 82 ]  The improved irrigator included features such as measuring the amount of liquid entering and exiting the colon as well as indicating and regulating the positive pressure of the pumped liquid. [ 82 ]


At the Battle Creek Sanitarium, these colonic irrigators were often used to shoot gallons of water up patients' rectums into their colons, sometimes followed by a half-pint yogurt enema to aid in further cleaning. It has been suggested that multiple people would get this treatment at one time. [ 74 ]


Synthesizing his Adventist beliefs with his scientific and medical knowledge, Kellogg created his idea of "biologic living". [ 15 ]  This was the idea that appropriate diet, exercise, and recreation was required to maintain a healthy body, mind, and soul. As such, the policies and therapies at the Battle Creek Sanitarium were very much in line with these principles of biologic living, such as the focus on vegetarianism or drinking 8–10 glasses of water a day. [ 83 ]  In fact, his belief that biologic living would protect his health was so strong that he did not even feel it necessary to get vaccinated against smallpox. [ 16 ] : 59


Kellogg's philosophy was presented in seven textbooks that were prepared for Adventist schools and colleges. In these, Kellogg put his main emphasis on the value of fresh air, exercise, and sunshine, and the dangers of alcohol and tobacco. [ 16 ] : 91   In terms of practice, Kellogg's biologic living was very similar to the methods of Christian physiologists, requiring sexual restraint, total abstinence from drugs, and a vegetarian diet. [ 16 ] : 44


Kellogg was a prominent member of the anti-tobacco consumption campaign, speaking out often on the issue. [ 84 ]  He believed that consumption of tobacco not only caused physiological damage, but also pathological, nutritional, moral, and economic devastation onto society. His belief was that "tobacco has not a single redeeming feature… and is one of the most deadly of all the many poisonous plants known to the botanist." [ 85 ]  His beliefs were very much in line with the prevailing view of the Adventists, who had become some of the most important supporters of the anti-tobacco movement.


In his 1922 book  Tobaccoism, or How Tobacco Kills , Kellogg cited many studies on the negative impacts of smoking, and went so far as to attribute the longer lifespan of women to the observation that they partook in tobacco less than their male counterparts. [ 85 ]


Kellogg also served as the president of the Michigan Anti-Cigarette Society, and after the First World War, he served as a member of the Committee of Fifty to Study the Tobacco Problem. This latter group included Henry Ford, George Peabody, and John Burroughs, and ended with the production of one of the first educational motion pictures against smoking. [ 16 ] : 107   Kellogg's work on several committees against smoking culminated in Utah Senator Reed Smoot introducing a bill to Congress in 1929 that aimed to put tobacco under the purview of the Pure Food and Drug Act. In the end, however, this measure failed to pass. [ 86 ]


Though alcoholic beverages were commonly used as a stimulant by the medical community during the time that Kellogg began his medical practice, he was firm in his opposition to the practice. [ 16 ]  The usage of alcohol as a remedy to anything was "an evil of stupendous proportions." [ 87 ]


Kellogg went against the prevailing notion of the time that alcohol was a stimulant. Citing contemporary research, Kellogg believed that alcohol could not be a stimulant because it lessened vital activity and depressed vital forces. [ 87 ]  Seeing its effects on plants, animals, and humans, he felt that alcohol was a poison. [ 87 ]  Kellogg noticed deleterious effects that alcohol had on both the brain, the digestive system, and the liver, among other organs.


In addition to the idea that alcohol was an unsuitable therapeutic tool, Kellogg also considered it to lead to mental and moral bankruptcy. [ 87 ]  Alcohol was "one of the devil's most efficient agents for destroying the happiness of man, both for the present and the hereafter." [ 87 ]  Even moderate drinkers were subject to these effects, as Kellogg felt that a poison was a poison in all doses.


Kellogg also opposed tea and coffee due to the  caffeine  content of those beverages. His view was that caffeine was a poison. [ 88 ]  Not only did he detail numerous physiological and developmental problems caused by caffeine, but he also suggested that caffeine usage could lead to moral deficiencies. He blamed the prevalence of these beverages not only on the prohibition of alcoholic beverages at the time, but also on the extensive marketing efforts organized by the producers of these products. Kellogg's view was that "nature has supplied us with pure water, with a great variety of fruit juices and wholesome and harmless flavors quite sufficient to meet all our needs." [ 89 ]


As early as the 1880s, Kellogg had prepared charts and lectures on the dangers of tobacco and alcohol, which were used widely by lecturers who encouraged temperance in their students. [ 16 ] : 106   In 1878, John Harvey Kellogg, along with Ellen G. White, the founder of the Seventh-day Adventists, and several others, had organized the American Health and Temperance Association. [ 16 ] : 107   The goal of this organization was to expose the far-reaching dangers of tobacco, alcohol, tea, and coffee. For the 15 years that the organization persisted, Kellogg remained as its president. [ 16 ] : 107


Kellogg has labeled the various uses of hydropathy as being byproducts of the many properties of water. In his 1876 book,  The Uses of Water in Health & Disease , he acknowledges both the chemical composition and physical properties of water. Hydrogen and oxygen, when separate, are two "colorless, transparent, and tasteless" gases, which are explosive when mixed. [ 90 ]  More importantly, water, he says, has the highest specific heat of any compound (although in actuality it does not). As such, the amount of heat and energy needed to elevate the temperature of water is significantly higher than that of other compounds like mercury. Kellogg addressed water's ability to absorb massive amounts of energies when shifting phases. He also highlighted water's most useful property, its ability to dissolve many other substances. [ 91 ]


According to Kellogg, water provides remedial properties partly because of vital resistance and partly because of its physical properties. For Kellogg, the medical uses of water begin with its function as a refrigerant, a way to lower body heat by way of dissipating its production as well as by conduction. "There is not a drug in the whole materia medica that will diminish the temperature of the body so readily and so efficiently as water." [ 92 ]  Water can also serve as a sedative. While other substances serve as sedatives by exerting their poisonous influences on the heart and nerves, water is a gentler and more efficient sedative without any of the negative side-effects seen in these other substances. Kellogg states that a cold bath can often reduce one's pulse by 20 to 40 beats per minute quickly, in a matter of a few minutes. Additionally, water can function as a tonic, increasing both the speed of circulation and the overall temperature of the body. A hot bath accelerates one's pulse from 70 to 150 beats per minute in 15 minutes. Water is also useful as an anodyne since it can lower nervous sensibility and reduce pain when applied in the form of hot fomentation. Kellogg argues that this procedure will often give one relief where every other drug has failed to do so. He also believed that no other treatment could function as well as an antispasmodic, reducing infantile convulsions and cramps, as water. Water can be an effective astringent as, when applied cold, it can arrest hemorrhages. Moreover, it can be very effective in producing bowel movements. Whereas purgatives would introduce "violent and unpleasant symptoms", water would not. Although it would not have much competition as an emetic at the time, Kellogg believed that no other substance could induce vomiting as well as water did. Returning to one of Kellogg's most admired qualities of water, it can function as a "most perfect eliminative". Water can dissolve waste and foreign matter from the blood. These many uses of water led Kellogg to belief that "the aim of the faithful physician should be to accomplish for his patient the greatest amount of good at the least expence  of vitality; and it is an indisputable fact that in a large number of cases water is just the agent with which this desirable end can be obtained." [ 93 ]


Although Kellogg praised hydropathy for its many uses, he did acknowledge its limits. "In nearly all cases, sunlight, pure air, rest, exercise, proper food, and other hygienic agencies are quite as important as water. Electricity, too, is a remedy which should not be ignored; and skillful surgery is absolutely indispensable in not a small number of cases." [ 94 ]  With this belief, he went on to criticize many medical figures who misused or overestimated hydropathy in the treating of disease. Among these, he criticized what he referred to as "Cold-Water Doctors" who would recommend the same remedy regardless of the type of ailment or temperament of the patient. [ 95 ]  These doctors would prescribe ice-cold baths in unwarmed rooms even during the harshest winters. In his opinion, this prejudicial approach to illness resulted in converting hydropathy to a more heroic type of treatment where many became obsessed with taking baths in ice-cold water. He addresses the negative consequences that resulted from this "infatuation", among them tuberculosis and other diseases. [ 96 ]  This dangerous habit was only exacerbated by physicians who used hydropathy in excess. Kellogg recounts an instance where a patient with a low typhus fever was treated with 35 cold packs while in a feeble state and, not to the surprise of Kellogg, died. Kellogg posits this excessive and dangerous use of hydropathy as a return to the "violent processes" of bloodletting, antimony, mercury and purgatives. [ 97 ]  Kellogg also criticizes the ignorance in "Hydropathic Quacks" as well as in Preissnitz, the founder of modern hydropathy, himself. Kellogg states that the "Quacks" as well as Preissnitz are ignorant for overestimating the hydropathy as a "cure-all" remedy without understanding the true nature of disease. [ 98 ]


Kellogg would live for over 60 years after writing  Plain Facts . He continued to work on healthy eating advice and run the sanitarium, although this was hit by the  Great Depression  and had to be sold. He ran another institute in Florida, which was popular throughout the rest of his life, [ 99 ]  although it was a distinct step down from his Battle Creek institute. [ 100 ]


In 1937, Kellogg received an honorary degree in Doctor of Public Service from  Oglethorpe University . [ 101 ]


Pulitzer Prize -winning historian  Will Durant , who had been a vegetarian since the age of 18, called Dr. Kellogg "his old mentor", [ 102 ]  and said that Dr. Kellogg, more than any other person since his high school days, had influenced his life. [ 103 ]


Kellogg became editor of the  Health Reformer  journal in 1874. The journal changed its name to  Good Health  in 1879 and Kellogg held his editorial position for many years until his death. [ 104 ]  The  Good Health  journal had more than 20,000 subscribers and was published until 1955. [ 105 ]


Kellogg was outspoken about his  views  on  race  and his belief in  racial segregation , regardless of the fact that he himself raised several  black  foster children. In 1906, together with  Irving Fisher  and  Charles Davenport , Kellogg founded the  Race Betterment Foundation , which became a major center of the new  eugenics movement in America . Kellogg was in favor of  racial segregation in the United States  and he also believed that immigrants and non-whites would damage the white American population's gene pool. [ 106 ]


He co-founded the  Race Betterment Foundation , [ 107 ]  co-organized several National Conferences on Race Betterment and attempted to create a 'eugenics registry'. Alongside discouraging 'racial mixing', Kellogg was in favor of sterilizing 'mentally defective persons', promoting a eugenics agenda while working on the Michigan Board of Health [ 108 ]  and helping to enact authorization to sterilize those deemed 'mentally defective' into state laws during his tenure. [ 109 ] [ 110 ]


Kellogg had a long personal and business split with his brother, after fighting in court for the rights to cereal recipes. The  Foundation for Economic Education  records that the nonagenarian J.H. Kellogg prepared a letter seeking to reopen the relationship. His secretary decided her employer had demeaned himself in it and refused to send it. The younger Kellogg did not see it until after his brother's death. [ 52 ] : 381–382


John Harvey Kellogg married  Ella Ervilla Eaton  of  Alfred Center, New York , on February 22, 1879. The couple maintained separate bedrooms and did not have any biological children. However, they were foster parents to 42 children, legally  adopting  8 of them, before Ella died in 1920. [ 111 ]  The adopted children included Agnes Grace, Elizabeth Ella, Harriett Eleanor, John William, Ivaline Maud, Paul Alfred, Robert Mofatt, and Newell Carey. [ 112 ]


Kellogg died on December 14, 1943, in  Battle Creek, Michigan . [ 7 ]  He was buried in Oak Hill Cemetery in Battle Creek. [ 52 ] : 385   In his will, Kellogg left his entire estate to the  Race Betterment Foundation . [ 52 ] : 321


British actor  Anthony Hopkins  plays a highly fictionalized Dr. J.H. Kellogg in the American 1994 film  The Road to Wellville  by Alan Parker. [ 113 ]  This film depicts the fire of the sanitarium building complex, and ends with Dr. Kellogg, years after, dying of a heart attack while diving from a high board.


Several  popular controversies  attribute various cultural practices, inventions, and historical events to Kellogg. [ 11 ] [ 12 ]  These include claims that  Kellogg's corn flakes  were invented and/or marketed to prevent masturbation. They were promoted to prevent indigestion, while the reason for their invention is, as of yet, inconclusive. [ 12 ]  Another  common claim  credits Kellogg with popularizing routine infant  circumcision  in the  United States  and broader  Anglosphere . [ 11 ]  This is a potential overstatement, [ 114 ]  although Kellogg did advocate circumcision, without anaesthetic, as an eficacious cure for masturbation. [ 115 ] : 659   He wrote in  Plain facts for old and young  that "Eminent physicians have expressed the opinion that the practice would be a salutary one for all men." [ 116 ] : 114   However in later editions, Kellogg came to criticize this growing belief among medical professionals, arguing that routine circumcision provided doubtful medical benefit, citing  iatrogenically  created  meatal stenosis  among the  Jewish  male population:


Eminent physicians have expressed the opinion that the practice would be a salutary one for all men...It is doubtful, however, whether as much harm as good does not result from circumcision, since it has been shown by extensive observation among the Jews that very great contraction of the meatus, or external orifice of the urethra, is exceedingly common among them, being undoubtedly the result of the prolonged irritation and subsequent cicatricial contraction resulting from circumcision in infancy. [ 117 ] : 107


The  King's College Criteria  or the  King's College Hospital criteria  were devised in 1989 to determine if there were any early indices of poor prognosis in patients with  acute liver failure .  Acute liver failure is defined as the onset of  encephalopathy  (altered mental status) or  coagulopathy  (altered bleeding tendencies) within 26 weeks of a patient diagnosed with liver disease.  Patients with  hepatitis B  acquired at birth,  Wilson's disease  and  autoimmune hepatitis  are included if their disease was identified within the past 26 weeks.  These patients are very ill, and have a very high risk of dying of their illness without adequate treatment which may include  liver transplantation .  It is important that physicians find ways of identifying patients with acute liver failure early in their course who will do poorly, and may require liver transplantation.  The King's College Criteria have consistently shown excellent  operating characteristics  for determining prognosis in these patients.  As  liver transplantation  becomes a more accessible option for patients with acute liver failure, the King's College Criteria serve a role in determining which patients may require transplantation. [ 1 ]


The King's College criteria were described in a seminal publication in 1989 by J.G. O'Grady and colleagues from  King's College School of Medicine . [ 2 ]   588 patients with acute liver failure who presented to King's College Hospital from 1973 to 1985 were assessed retrospectively to determine if there were particular clinical features or tests that correlated poorly with prognosis.  The criteria were stratified into acetaminophen and non-acetaminophen causes of acute liver failure, due to the different operating characteristics of parameters correlating with prognosis in the two causes. [ citation needed ]


Acetaminophen  (or  paracetamol ) is an  analgesic  medication that can affect the liver when administered in high doses.  Acetaminophen is predominantly conjugated into  glucuronate  and  sulfate  moieties by  Phase II metabolism .  A small percentage is metabolized by the  cytochrome P450  pathway to a toxic metabolite, NAPQI.  NAPQI is conjugated by  glutathione  to non-toxic cysteine and mercapturic acid moieties.  In cases of acetaminophen toxicity, the Phase II conjugation enzymes are saturated, and a higher fraction is converted to NAPQI.  The conjugation of NAPQI to glutathione occurs until glutathione is depleted from hepatic reserves, after which the toxic NAPQI accumulates and causes damage to the hepatocytes.  This occurs primarily in areas of the liver that are relatively poorly perfused with oxygen, or furthest away from the  hepatic artery , termed  Zone 3 .  Acetaminophen overdose is associated with Zone 3 necrosis, to the point that acute liver failure may result. [ 3 ]


The King's College Criteria identify two groups of patients that have a poor prognosis with acetaminophen induced liver failure:


There are many causes of acute liver failure aside from acetaminophen toxicity; these include viral hepatitis—including  hepatitis A  (rarely), [ 4 ]   hepatitis B , [ 1 ]   hepatitis C  (rarely), [ 5 ]   hepatitis E  (especially in pregnant women),  [ 6 ]   Epstein–Barr virus ,  cytomegalovirus  and  varicella zoster virus [ 1 ]  --  Wilson's disease , the toxin of the  death cap  mushroom ( Amanita phalloides ),  alcohol ,  autoimmune hepatitis ,  Budd–Chiari syndrome , other medications (including  halothane ,  hormonal contraception , and  isoniazid ), recreational drugs (including  ecstasy   [1] ) and, rarely, tumours infiltrating the liver. [ 1 ]


In patients with non-acetaminophen acute liver failure, the following criteria were identified as being associated with a poor prognosis: [ 2 ]


The utility of the criteria in determining the prognosis of patients with acute liver failure is defined by their operating characteristics.  The  positive predictive value  of the criteria in predicting death from acute liver failure has ranged from 70% to 100%. [ 1 ] [ 7 ] [ 8 ]   A Canadian  meta-analysis  assessing various prognostic indices found that the  specificity  of the King's College criteria in predicting  mortality  exceeded 90%, with a  sensitivity  of 69%. [ 9 ]   As a result, the American Society for Study of Liver Diseases has recommended the King's College Criteria as being helpful early parameters in ascertaining the need for  liver transplantation  in patients with acute liver failure. [ 1 ]


A variety of other calculations have been done based on similar parameters to determine the risk of mortality in acute liver failure. [ 1 ]   The Acute Physiology and Chronic Health Evaluation II ( APACHE II ) score has a comparable sensitivity to the King's College Criteria in determining prognosis. [ 9 ]


Lactulose  is a non-absorbable  sugar  used in the treatment of  constipation  and  hepatic encephalopathy . [ 3 ] [ 4 ]  It is administered  orally  for constipation, and either orally or  rectally  for  hepatic encephalopathy . [ 3 ]  It generally begins working after 8–12 hours, but may take up to 2 days to improve constipation. [ 1 ] [ 2 ]


Common  side effects  include abdominal  bloating  and cramps. [ 3 ]  A potential exists for  electrolyte problems  as a result of the  diarrhea  it produces. [ 3 ]  No evidence of harm to the fetus has been found when used during  pregnancy . [ 3 ]  It is generally regarded as safe during breastfeeding. [ 5 ]  It is classified as an  osmotic laxative . [ 6 ]


Lactulose was first made in 1929, and has been used medically since the 1950s. [ 7 ] [ 8 ]  Lactulose is made from the milk sugar  lactose , which is  composed of two simple sugars ,  galactose  and  glucose . [ 9 ] [ 3 ]  It is on the  World Health Organization's List of Essential Medicines . [ 10 ]  It is available as a  generic medication . [ 4 ]  In 2022, it was the 267th most commonly prescribed medication in the United States, with more than 900,000 prescriptions. [ 11 ] [ 12 ]


Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment. [ 13 ]  The dosage of lactulose for chronic idiopathic constipation is adjusted depending on the constipation severity and desired effect, from a mild stool softener to causing diarrhea. Lactulose is contraindicated in case of  galactosemia , as most preparations contain the monosaccharide galactose due to its synthesis process. [ 14 ] [ 15 ]


Lactulose may be used to counter the constipating effects of  opioids , and in the symptomatic treatment of  hemorrhoids  as a stool softener. [ medical citation needed ]


Lactulose is commonly prescribed for children who develop fear of their bowel movements and are withholders. This is because lactulose, when dosed in the proper amount, causes a bowel movement that is impossible to retain for very long. Lactulose is also used for the elderly because of its gentle and consistent results. [ medical citation needed ]


Lactulose is useful in treating  hyperammonemia  (high blood ammonia), which can lead to  hepatic encephalopathy . Lactulose helps trap the  ammonia  (NH 3 ) in the colon and bind to it. [ 16 ]   It does this by using gut flora to acidify the colon, transforming the freely diffusible ammonia into  ammonium  ions ( NH + 4 ), which can no longer diffuse back into the blood. [ 17 ]  It is also useful for preventing hyperammonemia caused as a side effect of administration of  valproic acid . [ 18 ]


Lactulose is used as a test of  small intestine bacterial overgrowth  (SIBO). Recently, the reliability of it for diagnosing SIBO has been seriously questioned. [ 19 ] [ 20 ] [ 21 ] [ 22 ]  A large amount of it is given with subsequent testing of molecular  hydrogen gas in the breath . The test is positive if an increase in exhaled hydrogen occurs before that which would be expected by normal  digestion by the normal  gut flora  in the colon. An earlier result has been hypothesized to indicate digestion occurring within the small intestine. An alternate explanation for differences in results is the variance in small bowel transit time among tested subjects. [ 22 ]


No evidence of harm to the fetus has been found when used during  pregnancy . [ 3 ]  It is generally regarded as safe during breastfeeding. [ 5 ]


Common side effects of lactulose are abdominal cramping,  borborygmus , and  flatulence . In normal individuals, overdose is considered uncomfortable, but not life-threatening. [ 23 ]  Uncommon side effects are  nausea  and  vomiting .  In sensitive individuals, such as the elderly or people with reduced  kidney  function, excess lactulose dosage can result in  dehydration  and electrolyte disturbances such as  low magnesium levels .  Ingestion of lactulose does not cause a weight gain because it is not digestible, with no nutritional value. Although lactulose is less likely to cause  dental caries  than sucrose, as a sugar, a potential for this exists, which is relevant when taken by people with a high susceptibility to this condition. [ citation needed ]


Lactulose is not absorbed in the  small intestine  nor broken down by human enzymes, thus stays in the digestive bolus through most of its course, causing retention of water through  osmosis  leading to softer, easier-to-pass stool. It has a secondary laxative effect in the colon, where it is  fermented  by the  gut flora , producing  metabolites  which have osmotic powers and  peristalsis -stimulating effects (such as  acetate ), but also  methane  associated with  flatulence . [ citation needed ]


Lactulose is metabolized in the  colon  by  bacterial flora  into short-chain fatty acids, including  lactic acid  and  acetic acid . These partially dissociate, acidifying the colonic contents (increasing the H +  concentration in the gut). [ 17 ]  This favors the formation of the nonabsorbable  NH + 4  from NH 3 , trapping NH 3  in the colon and effectively reducing plasma NH 3  concentrations. Lactulose is therefore effective in treating hepatic encephalopathy. [ 24 ]  Specifically, it is effective as secondary prevention of hepatic encephalopathy in people with cirrhosis. [ 25 ]  Moreover, research showed improved cognitive functions and health-related quality of life in people with cirrhosis with minimal hepatic encephalopathy treated with lactulose. [ 26 ]


Lactulose is a  disaccharide  formed from one molecule each of the  simple sugars  ( monosaccharides )  fructose  and  galactose . Lactulose is not normally present in raw milk, but is a product of heat processes: [ 27 ]  the greater the heat, the greater amount of this substance (from 3.5 mg/L in low-temperature  pasteurized  milk to 744 mg/L in in-container sterilized milk). [ 28 ]


Lactulose is produced commercially by  isomerization  of  lactose . A variety of reaction conditions and catalysts can be used. [ 14 ]


Lactulose  is its  international nonproprietary name  (INN). [ 29 ]  It is sold under various brand names. [ citation needed ]


Lactulose is available as a  generic medication . [ 4 ]  It is available without prescription in most countries, but a prescription is required in the United States, [ 3 ]  Philippines, and Austria. [ citation needed ]


In some countries where lactulose may be obtained without a prescription, lactulose is commonly used as a  food additive  to improve taste and promote intestinal transit. [ citation needed ]


Lactulose is used in veterinary medicine. [ 30 ]


Laminarid  is a blend of  polysaccharides , proteins and salts of  alginic acid  obtained from  sea cabbage  (Laminariae thalli [ citation needed ] ). It is an  osmotic laxative . [ 1 ]


This  drug  article relating to the  gastrointestinal system  is a  stub . You can help Wikipedia by  expanding it .


Laparoscopic hernia repair  is the repair of a  hiatal hernia  using a  laparoscope , which is a tiny telescope-like instrument. [ 1 ] [ 2 ] [ 3 ] [ 4 ]  A hiatal hernia is the protrusion of an organ through its wall or cavity. [ 5 ]  There are several different methods that can be used when performing this procedure. Among them are the Nissen Fundoplication and the general laparoscopic hernia repair.


There are two types of hiatal hernias. The two different types of hiatal hernias that are relevant to this surgery are rolling hiatal hernias and sliding hiatal hernias. A type II, rolling hiatal hernia, is when the  gastric fundus  is herniated, but the cardia portion of the stomach remains still. A type 1, or sliding hiatal hernia, is when the gastroesophageal junction and the cardia portion of the stomach move through the posterior  mediastinum . [ 5 ]


There are several different methods when performing a laparoscopic hernia repair. A few of these are the fundoplication and the general laparoscopic hernia repair.


In  bariatric surgery , hernias are repaired  laparoscopically  anteriorly, rather than posteriorly as in the  fundoplication  procedure.  This general laparoscopic procedure was introduced by Sami Salem Ahmad from Germany.
The  Nissen fundoplication  procedure was first performed by  Rudolph Nissen  in 1955. [ citation needed ]


A laparoscopic hernia repair is when the hiatal hernia is corrected using a covering for the mesh that is used to repair the weakened area. The defect is then measured and the mesh is stapled into place. [ 6 ]  A benefit of performing Laparoscopic hernia repair is shorter recovery times compared to other methods. However, it is a longer procedure than most other methods of repair. [ 7 ]


The  Nissen fundoplication  procedure consists of a 360 degree transabdominal  fundoplication . A fundoplication is the suturing of the fundus located in the stomach and around the esophagus. [ 5 ]  The procedure itself is performed with the patient in a low lithotomy position at approximately 25 degrees. After the esophagus is mobilized, the  crura  is moved posteriorly using sutures to make room for a French bougie. When in place, a wrap is created and sutured to the esophagus and to the right  crus  at the hiatus as well. After this is performed, the bougie is removed and the wrap is further anchored with additional sutures. The  trocar  sites are then closed. [ 5 ]


When performing a laparoscopic hernia repair, patients undergoing the procedure face complications such as postoperative urinary retention (PUR).
Another potential complication is requiring a second hernia repair after previously having one at an earlier time. [ 8 ]
Some complications can arise from the need for general anesthesia in having an open ventral hernia repair. [ 9 ]  Inherent risks are associated with the use of anesthesia.


General complications that can occur using any method of hernia repair are: [ 10 ]


Some complications that can arise from the general laparoscopic procedure are PUR (postoperative urinary retention)  [ 11 ]


Other complications that can arise during this procedure are: [ 12 ]


Complications that can arise form this procedure are: [ 5 ]


Overall, the complication rate for this procedure is about 10% to 20%. The failure rate, or inability to repair the hernia, is approximately 5%. [ 5 ]


The outcomes of laparoscopic hernia repair versus open hernia repair support laparoscopic hernia repair as the method of choice.
Outcomes from having laparoscopic hernia repair are: [ 13 ]


A laparoscopic hiatal hernia repair results in a hospital stay of approximately 36 to 48 hours after the procedure has been performed  [ 5 ]


Laparoscopic hernia repair has several benefits compared to performing Open hernia repairs. [ citation needed ]


Benefits are: [ 5 ]


Laxatives ,  purgatives , or  aperients  are substances that loosen  stools [ 1 ]  and increase  bowel movements . They are used to treat and prevent  constipation .


Laxatives vary as to how they work and the side effects they may have. Certain  stimulant ,  lubricant , and  saline  laxatives are used to evacuate the  colon  for  rectal  and bowel examinations, and may be supplemented by  enemas  under certain circumstances. Sufficiently high doses of laxatives may cause  diarrhea . Some laxatives combine more than one active ingredient, and may be administered  orally  or  rectally .


Bulk-forming laxatives, also known as  roughage , are substances, such as  fiber  in food and  hydrophilic  agents in  over-the-counter drugs , that add bulk and water to  stools  so they can pass more easily through the  intestines  (lower part of the  digestive tract ). [ 2 ]


Properties


Bulk-forming agents generally have the gentlest of effects among laxatives, [ 1 ]  making them ideal for long-term maintenance of regular bowel movements.


Foods that help with laxation include fiber-rich foods.  Dietary fiber  includes  insoluble fiber  and  soluble fiber , such as: [ 4 ]


Emollient laxatives, also known as stool softeners, are  anionic surfactants  that enable additional water and fats to be incorporated in the stool, making movement through the bowels easier.


Emollient agents prevent constipation rather than treating long-term constipation. [ 3 ]


Lubricant  laxatives are substances that coat the stool with slippery lipids and decrease colonic absorption of water so the stool slides through the colon more easily. Lubricant laxatives also increase the weight of stool and decrease intestinal transit time. [ 9 ]


Mineral oils , such as  liquid paraffin , are generally the only nonprescription lubricant laxative available, but due to the risk of lipid pneumonia resulting from accidental aspiration, mineral oil is not recommended, especially in children and infants. [ 10 ] [ 11 ]  Mineral oil may decrease the absorption of fat-soluble vitamins and some minerals. [ 9 ]


Hyperosmotic  laxatives cause the intestines to hold more water, creating an  osmotic gradient , which adds more pressure and stimulates bowel movement. [ 12 ] [ 10 ]


Lactulose  works by the  osmotic  effect, which retains water in the colon; lowering the  pH  through bacterial fermentation to lactic, formic, and acetic acids; and increasing colonic  peristalsis . Lactulose is also indicated in  portal-systemic encephalopathy . Glycerin suppositories work mostly by hyperosmotic action, but the  sodium stearate  in the preparation also causes local irritation to the colon. [ citation needed ]


Solutions of  polyethylene glycol  and electrolytes ( sodium chloride ,  sodium bicarbonate ,  potassium chloride , and sometimes  sodium sulfate ) are used for  whole bowel irrigation , a process designed to prepare the bowel for surgery or  colonoscopy  and to treat certain types of  poisoning . Brand names for these solutions include GoLytely, GlycoLax, Cosmocol, CoLyte, Miralax, Movicol, NuLytely, Suprep, and Fortrans. Solutions of  sorbitol  (SoftLax) have similar effects. [ citation needed ]


Saline laxatives are nonabsorbable, osmotically active substances that attract and retain water in the intestinal lumen, increasing intraluminal pressure that mechanically stimulates evacuation of the bowel. Magnesium-containing agents also cause the release of  cholecystokinin , which increases intestinal motility and fluid secretion. [ 3 ]  Saline laxatives may alter a patient's fluid and electrolyte balance.


Stimulant laxatives are substances that act on the intestinal  mucosa  or  nerve plexus , altering water and  electrolyte  secretion. [ 13 ]  They also stimulate peristaltic action and can be dangerous under certain circumstances. [ 14 ]


Prolonged use of stimulant laxatives can create drug dependence by damaging the colon's  haustral folds , making users less able to move feces through their colon on their own. A study of patients with chronic constipation found that 28% of chronic stimulant laxative users lost haustral folds over the course of one year, while none of the control group did. [ 15 ]


Castor oil  is a glyceride that is hydrolyzed by pancreatic lipase to  ricinoleic acid , which produces laxative action by an unknown mechanism.


Long-term use of castor oil may result in loss of fluid, electrolytes, and nutrients. [ 3 ]


These are motility stimulants that work through activation of  5-HT 4  receptors of the  enteric nervous system  in the  gastrointestinal tract . However, some have been discontinued or restricted due to potentially harmful cardiovascular side effects.


Tegaserod  (brand name  Zelnorm ) was removed from the general U.S. and Canadian markets in 2007, due to reports of increased risks of heart attack or stroke. It is still available to physicians for patients in emergency situations that are life-threatening or require hospitalization. [ 16 ]


Prucalopride  (brand name Resolor) is a current drug approved for use in the EU since October 15, 2009, [ 17 ]  in Canada (brand name Resotran) since December 7, 2011, [ 18 ]  and in the United States since December 2018.


Lubiprostone  is used in the management of chronic idiopathic constipation and irritable bowel syndrome. It causes the intestines to produce a chloride-rich fluid secretion that softens the stool, increases motility, and promotes spontaneous bowel movements.


For adults, a  randomized controlled trial  found  PEG  (MiraLax or GlycoLax) 17 grams once per day to be superior to  tegaserod  at 6 mg twice per day. [ 21 ]  A randomized controlled trial found greater improvement from two sachets (26 g) of PEG versus two sachets (20 g) of lactulose. [ 22 ]  17 g per day of PEG has been effective and safe in a randomized, controlled trial for six months. [ 23 ]  Another randomized, controlled trial found no difference between sorbitol and lactulose. [ 24 ]


For children, PEG was found to be more effective than lactulose. [ 25 ]


Some of the less significant adverse effects of laxative abuse include  dehydration  (which causes tremors, weakness, fainting, blurred vision, kidney damage),  low blood pressure ,  fast heart rate , postural dizziness and  fainting ; [ 26 ]  however, laxative abuse can lead to potentially fatal  acid-base , and  electrolyte imbalances . [ 26 ]  For example, severe  hypokalaemia  has been associated with  distal renal tubular acidosis  from laxative abuse. [ 26 ]   Metabolic alkalosis  is the most common acid-base imbalance observed. [ 26 ]  Other significant adverse effects include  rhabdomyolysis , [ 26 ]   steatorrhoea , [ 26 ]   inflammation  and  ulceration  of colonic mucosa, [ 26 ]   pancreatitis , [ 26 ] [ 27 ]   kidney failure , [ 26 ] [ 28 ] [ 29 ]   factitious diarrhea [ 26 ] [ 30 ]  and other problems. [ 26 ]  The colon will need more quantities of laxatives to keep functioning, this will result in a lazy colon, infections, irritable bowel syndrome, and potential liver damage.


Although some patients with eating disorders such as  anorexia nervosa  and  bulimia nervosa  abuse laxatives in an attempt to lose weight, laxatives act to speed up the transit of feces through the large intestine, which occurs after the absorption of nutrients in the small intestine is already complete. Thus, studies of laxative abuse have found that effects on body weight reflect primarily temporary losses of body water rather than energy (calorie) loss. [ 26 ] [ 31 ] [ 32 ]


Physicians warn against the chronic use of stimulant laxatives due to concern that chronic use could cause the colonic tissues to get worn out over time and not be able to expel feces due to long-term overstimulation. [ 33 ]   A common finding in patients having used stimulant laxatives is a brown pigment deposited in the intestinal tissue, known as  melanosis coli . [ citation needed ]


Laxatives, once called "physicks" or "purgatives", were used extensively in  historic medicine  to treat many conditions for which they are now generally regarded as ineffective in  evidence-based medicine . [ 34 ]  Likewise, laxatives (often termed  colon cleanses ) may be promoted in  alternative medicine  for various conditions of  quackery , such as " mucoid plaque ". [ 35 ]


Leaky gut syndrome  is a hypothetical and medically unrecognized condition [ 1 ] [ 2 ]  that is distinct from the scientific phenomenon of  increased intestinal permeability  commonly known as "leaky gut". [ 1 ] [ 3 ]  Claims for the existence of "leaky gut syndrome" as a distinct medical condition come mostly from nutritionists and practitioners of  alternative medicine . [ 1 ] [ 4 ] [ 5 ]  Proponents claim that a "leaky gut" causes  chronic inflammation  throughout the body that results in a wide range of conditions, including  myalgic encephalomyelitis/chronic fatigue syndrome ,  rheumatoid arthritis ,  lupus ,   migraines ,  multiple sclerosis , and  autism . [ 1 ] [ 4 ]  There is little evidence to support this hypothesis. [ 1 ] [ 6 ]


Stephen Barrett  has described "leaky gut syndrome" as a  fad  diagnosis and says that its proponents use the alleged condition as an opportunity to sell a number of alternative-health remedies – including diets, herbal preparations, and dietary supplements. [ 5 ]  Promoters of  pseudoscience  have claimed that the passage of proteins through a "leaky" gut is the cause of autism. [ 7 ]  Evidence for claims that a leaky gut causes autism is weak and conflicting. [ 8 ]


Advocates tout various treatments for "leaky gut syndrome", such as  dietary supplements ,  probiotics , herbal remedies,  gluten -free foods, and low- FODMAP , low-sugar, and/or antifungal diets, but there is little evidence that the treatments offered are of benefit. [ 1 ]
None have been adequately tested to determine whether they are safe and effective for this purpose. [ 4 ]  The U.K.  National Institute for Health and Care Excellence  (NICE) does not recommend the use of any special diets to manage the main symptoms of autism or leaky gut syndrome. [ 1 ]


The  Lichtiger Colitis Activity Index  is a tool used in clinical research to measure quantify the impact of symptoms of  ulcerative colitis . [ 1 ]


The  Lille Model  is a medical modeling tool for predicting mortality in patients with  alcoholic hepatitis  who are not responding to steroid therapy. The model risk stratifies patients who have been receiving steroid treatment for seven days to predict who will improve and who should be considered for alternative treatment options including early referral for transplant. [ citation needed ]


The model is based on:


Initial model was based on a study of 238 patients and published in the Journal of Hepatology in 2003. [ 1 ]   Recent cohort studies demonstrate that those with a Lille score above 0.45 are likely non-responders to steroid therapy. [ 2 ]


Lipoprotein-X  ( Lp-X ) is an abnormal  low density lipoprotein  found in  cholestasis .


Lipoprotein-X is a lamellar particle of 30 to 70 nm in diameter as revealed by  electron microscopy . It is characterized by its high content of  phospholipids  (66% by weight) and unesterified  cholesterol  (22%), and its low content of  protein  (6%), cholesterol esters (3%), and  triglycerides  (3%). The protein component is dominated by  albumin , located in the core, and by  apolipoprotein  C, located on the surface of the particle. Using zonal ultracentrifugation, lipoprotein-X can be divided into three distinct populations: Lp-X1, Lp-X2, and Lp-X3, differing in density and apolipoprotein composition.


The pathogenesis of lipoprotein-X in cholestasis is not totally resolved. Normally, the  liver  excretes lipoprotein complexes into the bile showing phospholipid and unesterified cholesterol concentrations similar to Lipoprotein-X. The in vitro incubation of these  bile  lipoproteins with serum or albumin leads to the appearance of Lp-X–like particles. These findings suggest that the reflux of  bile  into the plasma compartment causes the formation of lipoprotein-X in  cholestasis  as a result of a physicochemical, nonmetabolic process. On the other hand, lipoprotein-X particles found in familial LCAT deficiency are identical to those in cholestasis regarding ultrastructure and biochemical composition. It has been supposed that reduced LCAT activities, common in patients with hepatocellular disease, cause, alone or in combination with other factors, the formation of Lipoprotein-X in cholestasis. Lipoprotein-X is mainly removed by the reticuloendothelial system of the liver and the  spleen , as shown by studies using radioactively labeled lipoprotein-X in rats. Other organs, such as the  kidney , also actively clear Lipoprotein-X from the plasma.


Liver function tests  ( LFTs  or  LFs ), also referred to as a hepatic panel or liver panel, are groups of blood tests that provide information about the state of a patient's  liver . [ 1 ]  These tests include  prothrombin time  (PT/INR),  activated partial thromboplastin time  (aPTT),  albumin ,  bilirubin  (direct and indirect), and others. The liver transaminases  aspartate transaminase (AST or SGOT)  and  alanine transaminase (ALT or SGPT)  are useful biomarkers of liver injury in a patient with some degree of intact liver function. [ 2 ] [ 3 ] [ 4 ]


Most  liver diseases  cause only mild symptoms initially, but these diseases must be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance.  This testing is performed on a patient's blood sample. Some tests are associated with functionality (e.g., albumin), some with cellular integrity (e.g.,  transaminase ), and some with conditions linked to the biliary tract ( gamma-glutamyl transferase  and  alkaline phosphatase ). Because some of these tests do not measure function, it is more accurate to call these liver chemistries or liver tests rather than liver function tests. [ 5 ]


Several biochemical tests are useful in the evaluation and management of patients with hepatic dysfunction. These tests can be used to detect the presence of liver disease. They can help distinguish among different types of liver disorders, gauge the extent of known liver damage, and monitor the response to treatment. Some or all of these measurements are also carried out (usually about twice a year for routine cases) on individuals taking certain medications, such as anticonvulsants, to ensure that these medications are not adversely impacting the person's liver. [ citation needed ]


Standard liver tests for assessing liver damage include alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Bilirubin may be used to estimate the excretory function of the liver and coagulation tests and albumin can be used to evaluate the metabolic activity of the liver. [ 6 ]


Although example reference ranges are given, these will vary depending on method of analysis used at the administering laboratory, as well as age, gender, ethnicity, and potentially unrelated health factors. Individual results should always be interpreted using the reference range provided by the laboratory that performed the test. [ 7 ]


Measurement of total  bilirubin  includes both unconjugated (indirect) and conjugated (direct) bilirubin. Unconjugated bilirubin is a breakdown product of  heme  (a part of  hemoglobin  in red blood cells). The liver is responsible for clearing the blood of unconjugated bilirubin, by 'conjugating' it (modified to make it water-soluble) through an enzyme named  UDP-glucuronyl-transferase . When the total bilirubin level exceeds 17 μmol/L, it indicates liver disease. When total bilirubin levels exceed 40 μmol/L, bilirubin deposition at the sclera, skin, and mucous membranes will give these areas a yellow colour, thus it is called  jaundice . [ 6 ]


The increase in predominantly unconjugated bilirubin is due to overproduction, reduced hepatic uptake of the unconjugated bilirubin and reduced conjugation of bilirubin. Overproduction can be due to the reabsorption of a  haematoma  and ineffective  erythropoiesis  leading to increased red blood cell destruction.  Gilbert's syndrome  and  Crigler–Najjar syndrome  have defects in the  UDP-glucuronyl-transferase  enzyme, affecting bilirubin conjugation. [ 6 ]


The degree of rise in conjugated bilirubin is directly proportional to the degree of hepatocyte injury. Viral  hepatitis  can also cause the rise in conjugated bilirubin. In parenchymal liver disease and incomplete extrahepatic obstruction, the rise in conjugated bilirubin is less than the complete  common bile duct  obstruction due to malignant causes. In  Dubin–Johnson syndrome , a mutation in  multiple drug-resistance protein 2 (MRP2)  causes a rise in conjugated bilirubin. [ 6 ]


In  acute appendicitis , total bilirubin can rise from 20.52 μmol/L to 143 μmol/L. In pregnant women, the total bilirubin level is low in all three trimesters. [ 6 ]


The measurement of bilirubin levels in the newborns is done through the use of bilimeter or transcutanoeus bilirubinometer instead of performing LFTs. When the total serum bilirubin increases over 95th percentile for age during the first week of life for high risk babies, it is known as hyperbilirubinemia of the newborn ( neonatal jaundice ) and requires  light therapy  to reduce the amount of bilirubin in the blood. Pathological jaundice in newborns should be suspected when the serum bilirubin level rises by more than 5 mg/dL per day, serum bilirubin more than the physiological range, clinical jaundice more than 2 weeks, and conjugated bilirubin (dark urine staining clothes).  Haemolytic jaundice  is the commonest cause of pathological jaundice. Those babies with Rh hemolytic disease, ABO incompatibility with the mother,  Glucose-6-phosphate dehydrogenase  (G-6-PD) deficiency and minor blood group incompatibility are at increased risk of getting haemolytic jaundice. [ 9 ]


Apart from being found in high concentrations in the liver, ALT is found in the kidneys, heart, and muscles. It catalyses the  transamination  reaction, and only exists in a cytoplasmic form. Any kind of liver injury can cause a rise in ALT. A rise of up to 300 IU/L is not specific to the liver, but can be due to the damage of other organs such as the kidneys or muscles. When ALT rises to more than 500 IU/L, causes are usually from the liver. It can be due to hepatitis, ischemic liver injury, and toxins that causes liver damage. The ALT levels in  hepatitis C  rises more than in hepatitis A and B. Persistent ALT elevation more than 6 months is known as  chronic hepatitis .  Alcoholic liver disease ,  non-alcoholic fatty liver disease  (NAFLD), fat accumulation in liver during childhood obesity,  steatohepatitis  (inflammation of fatty liver disease) are associated with a rise in ALT. Rise in ALT is also associated with reduced insulin response, reduced glucose tolerance, and increased free  fatty acids  and  triglycerides . Bright liver syndrome (bright liver on ultrasound suggestive of fatty liver) with raised ALT is suggestive of  metabolic syndrome . [ 6 ]


In pregnancy, ALT levels would rise during the second trimester. In one of the studies, measured ALT levels in pregnancy-related conditions such as  hyperemesis gravidarum  was 103.5 IU/L,  pre-eclampsia  was 115,  HELLP syndrome  was 149. ALT levels would reduce by greater than 50% in three days after child delivery. Another study also shows that  caffeine  consumption can reduce the risk of ALT elevation in those who consume alcohol, overweight people, impaired glucose metabolism, and viral hepatitis. [ 6 ]


AST exists in two  isoenzymes  namely mitochondrial form and cytoplasmic form. It is found in highest concentration in the liver, followed by heart, muscle, kidney, brain, pancreas, and lungs. [ 10 ]  This wide range of AST containing organs makes it a relatively less specific indicator of liver damage compared to ALT. An increase of mitochondrial AST in bloods is highly suggestive of tissue  necrosis  in  myocardial infarction  and chronic liver disease. More than 80% of the liver AST activity are contributed by mitochondrial form of the isoenzymes, while the circulating AST in blood are contributed by cytoplasmic form of AST. AST is especially markedly raised in those with  liver cirrhosis . [ 6 ]  AST can be released from a variety of other tissues and if the elevation is less than two times the normal AST, no further workup needs to be performed if a patient is proceeding to surgery. [ citation needed ]


In certain pregnancy related conditions such as hyperemesis gravidarum, AST can reach as high as 73 IU/L, 66 IU/L in pre-eclampsia, and 81 IU/L in HELLP syndrome. [ 6 ]


The AST/ALT ratio increases in liver functional impairment. In alcoholic liver disease, the mean ratio is 1.45, and mean ratio is 1.33 in post necrotic liver cirrhosis. Ratio is greater than 1.17 in viral cirrhosis, greater than 2.0 in alcoholic hepatitis, and 0.9 in non-alcoholic hepatitis. Ratio is greater than 4.5 in  Wilson disease  or  hyperthyroidism . [ 6 ]


Alkaline phosphatase  (ALP) is an enzyme in the cells lining the  biliary ducts  of the liver.  It can also be found on the mucosal epithelium of the small intestine,  proximal convoluted tubule  of the kidneys, bone, liver, and placenta. It plays an important role in lipid transposition in small intestines and calcification of bones. 50% of all the serum ALP activities in blood are contributed by bone. Acute viral hepatitis usually has normal or increased ALP. For example, hepatitis A has increased ALP due to  cholestasis  (impaired bile formation or bile flow obstruction) and would have the feature of prolonged itching. Other causes include: infiltrative liver diseases, granulomatous liver disease, abscess,  amyloidosis  of the liver and  peripheral arterial disease . Mild elevation of ALP can be seen in liver cirrhosis, hepatitis, and  congestive cardiac failure . Transient  hyperphosphataemia  is a benign condition in  infants , and can reach normal level in 4 months. In contrast, low levels of ALP is found in  hypothyroidism ,  pernicious anemia ,  zinc deficiency , and  hypophosphatasia . [ 6 ]


ALP activity is significantly increased in the third trimester of  pregnancy . [ 11 ]  This is due to increased synthesis from the  placenta  as well as increased synthesis in the  liver  induced by large amounts of estrogens. [ 11 ] [ 12 ] [ 13 ]  Levels in the third trimester can be as much as 2-fold greater than in non-pregnant women. [ 11 ]  As a result, ALP is not a reliable marker of hepatic function in pregnant women. [ 11 ]  In contrast to ALP, levels of ALT, AST, GGT, and  lactate dehydrogenase  are only slightly changed or largely unchanged during pregnancy. [ 11 ]   Bilirubin  levels are significantly decreased in pregnancy. [ 11 ]


In pregnancy conditions such as hyperemesis gravdirum, ALP levels can reach 215 IU/L, meanwhile, in pre-eclampsia, ALP can reach 14 IU/L, and in HELLP syndrome ALP levels can reach 15 IU/L. [ 6 ]


GGT is a microsomal enzyme found in hepatocytes, biliary epithelial cells, renal tubules, pancreas, and intestines. It helps in  glutathione  metabolism by transporting peptides across the cell membrane. Much like ALP, GGT measurements are usually elevated if cholestasis is present. [ 10 ]  In acute viral hepatitis, the GGT levels can peak at 2nd and 3rd week of illness, and remained elevated at 6 weeks of illness. GGT is also elevated in 30% of the hepatitis C patients. GGT can increase by 10 times in alcoholism. GGT can increase by 2 to 3 times in 50% of the patients with non-alcoholic liver disease. When GGT levels is elevated, the  triglyceride  level is elevated also. With insulin treatment, the GGT level can reduce. Other causes of elevated GGT are: diabetes mellitus,  acute pancreatitis , myocardial infarction,  anorexia nervosa ,  Guillain–Barré syndrome , hyperthyroidism, obesity and  myotonic dystrophy . [ 6 ]


In pregnancy conditions GGT activity is reduced in 2nd and 3rd trimesters. In hyperemesis gravidarum, GGT level value can reach 45 IU/L, 17 IU/L in pre-eclampsia, and 35 IU/L in HELPP syndrome. [ 6 ]


Albumin  is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein (the remaining constituents are primarily  globulins ). Albumin levels are decreased in chronic liver disease, such as  cirrhosis . It is also decreased in  nephrotic syndrome , where it is lost through the urine.  The consequence of low albumin can be edema since the intravascular  oncotic pressure  becomes lower than the extravascular space. An alternative to albumin measurement is prealbumin, which is better at detecting acute changes (half-life of albumin and prealbumin is about 2 weeks and about 2 days, respectively). [ 14 ] [ 15 ]


Other tests are requested alongside LFT to rule out specific causes.