Basic Principles of Nutrition in Patients With Cancer
Head midline position for preventing the occurrence or extension of germinal matrix-intraventricular hemorrhage in preterm infants. We can afford to overeat sugar if we store it as fat, and then use the fat as fuel over time. Lifestyle intervention to address these factors appears to be a critical component of any therapeutic approach. Heparin for prolonging peripheral intravenous catheter use in neonates. The mechanisms of activity reviewed include alkylating agents, topoisomerase poisons, DNA synthesis inhibitors, protein synthesis inhibitors, immunoceuticals, and lipoxygenase inhibitors. At the time of writing the article he is on the diet for 15 months and is free of symptoms as well as side effects. The third congress of the society is slated to meet in May in Washington, D.
Impediments to Adequate Nutrition
Because of the varying formulations some product preparations differ from country to country from a single manufacturer , the ingredients most responsible for benefiting surgical outcome aren't easily identified.
A synergy among the ingredients could play an important role. Arginine is essential for the functioning of immune cells and operates as a precursor to proline and polyamines, which are necessary for tissue repair and wound healing. ONS There's much more research on the effect of ONS products on surgical outcome, and they've been shown in several studies to reduce postsurgical complications.
Some also contain arginine and omega-3s, but in lesser amounts than IN products. Hydration, Carbohydrate Loading, and Muscle Strengthening While six to 12 hours of fasting before surgery currently is the norm, Evans said long periods of fasting can lead to insulin resistance, hyperglycemia, failure to achieve a postsurgery anabolic state, and sometimes, the need for insulin. Rather, he said, carbohydrate loading before surgery may be beneficial for ease of recovery.
Carbohydrate-loading protocols are common in other countries, but there are no such protocols in the United States. Hydration before surgery also is important. Studies show that when patients are well hydrated, they report less pain and nausea after surgery. Despite the fact that prolonged fasting before surgery is the norm, the American Society of Anesthesiologists suggests that patients can consume clear liquids up to two hours before surgery with no increased risk of aspiration.
Because surgery puts the body in a catabolic state, building lean body mass with increased protein intake and exercise before the procedure may increase the ease of recovery. Again, no specific protocols are in place, but increasing protein intake along with exercise, when possible, should be encouraged. Who Needs Preoperative Nutrition? While nearly everyone potentially can benefit from a preoperative nutritional assessment and therapy, not everyone will benefit equally.
There's a need to first identify the high- vs low-nutrition risk patients and the surgeries that pose high vs low nutrition risk. The American Academy of Hospice and Palliative Medicine suggests that providers facilitate respectful and informed discussions about the effects of artificial nutrition and hydration near the end of life among physicians, other health care professionals, patients, and families.
Ideally, patients will make their own decisions on the basis of a careful assessment of potential benefits and burdens, consistent with legal and ethical norms that permit patients to accept or forgo specific medical interventions.
Decisions about whether to provide artificial nutrition and hydration to patients in the late stages of life are complex and influenced by ethical, legal, cultural, and clinical considerations, and by patient and family preferences. Guidelines on the ethical considerations about whether to forgo or discontinue hydration and nutrition support have been published by a number of organizations, including the American Medical Association,[ 25 ] the American Academy of Hospice and Palliative Medicine,[ 11 ] the Hospice and Palliative Nurses Association,[ 18 ] the American Society for Parenteral and Enteral Nutrition,[ 26 , 27 ] and the Academy of Nutrition and Dietetics.
Religion and religious traditions provide a set of core beliefs about life events and an ethical foundation for clinical decision-making. To provide an optimal and inclusive healing environment, all palliative team members need to be aware of their own spirituality and how it may differ from that of fellow team members and the spirituality of the patients and families they serve.
Religious beliefs are often closely related to cultural views. Individuals living in the midst of a particular tradition can continue to be influenced by it, even if they have stopped believing in or practicing it. Patients may rely on religion and spirituality as important means to interpret and cope with illness. The wide range of practices related to neutropenic diets reflects the lack of evidence regarding the efficacy of dietary restrictions in preventing infectious complications in cancer patients.
Studies evaluating various approaches to diet restrictions have not shown clear benefit. A meta-analysis and a systematic review of articles evaluating the effect of a neutropenic diet on infection and mortality rates in cancer patients found no superiority or advantage in using a neutropenic diet over a regular diet in neutropenic cancer patients. Even after the observational study was omitted from the analysis, the results persisted.
The review concluded that these individual studies provided no evidence showing that the use of a low-bacterial diet prevents infections. Other studies have demonstrated potential adverse effects of neutropenic diets. One group of investigators [ 6 ] conducted a retrospective review of patients who had undergone hematopoietic cell transplantation HCT. The patients who received the neutropenic diet experienced significantly more documented infections than did the patients receiving the general hospital diet that permitted black pepper and well-washed fruits and vegetables and excluded raw tomatoes, seeds, and nuts.
The neutropenic diet group had a significantly higher rate of infections that could be attributed to a gastrointestinal source, as well as a trend toward a higher rate of vancomycin-resistant enterococci infections. Without clinical evidence to define the dietary restrictions required to prevent foodborne infection in immunocompromised cancer patients, recommendations for food safety are based on general food safety guidelines and the avoidance of foods most likely to contain pathogenic organisms.
The effectiveness of these guidelines is dependent on patient and caregiver knowledge about, and adherence to, safe food handling practices and avoidance of higher-risk foods. Leading cancer centers provide guidelines for HCT patients and information about food safety practices related to food purchase, storage, and preparation e.
Comprehensive food safety information designed by the U. Food and Drug Administration for people with cancer and for transplant recipients is also available online.
Recommendations support the use of safe food handling procedures and avoiding consumption of foods that pose a high risk of infection, as noted in Table 7. Maintaining adequate nutrition while undergoing treatment for cancer is imperative because it can reduce treatment-related side effects, prevent delays in treatment, and help maintain quality of life.
Patients are likely to search the Internet and other lay sources of information for dietary approaches to manage cancer risk and to improve prognosis. Unfortunately, much of this information is not supported by a sufficient evidence base.
The sections below summarize the state of the science on some of the most popular diets and dietary supplements. A vegetarian diet is popular, is easy to implement and, if followed carefully, does not result in nutrition deficiencies.
There is strong evidence that a vegetarian diet reduces the incidence of many types of cancer, especially cancers of the gastrointestinal GI tract. There are no published clinical trials, pilot studies, or case reports on the effectiveness of a vegetarian diet for the management of cancer therapy and symptoms.
There is no evidence suggesting a benefit of adopting a vegetarian or vegan diet upon diagnosis or while undergoing cancer therapy. On the other hand, there is no evidence that an individual who follows a vegetarian or vegan diet before cancer therapy should abandon it upon starting treatment.
One pilot study has suggested that following a plant-based diet can prevent tumor progression in men with localized prostate cancer. It is a high-carbohydrate, low-fat, plant-based diet stemming from philosophical principles promoting a healthy way of living. Although there are anecdotal reports on the effectiveness of a macrobiotic diet as an alternative cancer therapy, none have been published in peer-reviewed, scientific journals.
No clinical trials, observational studies, or pilot studies have examined the diet as a complementary or alternative therapy for cancer. In fact, two reviews of the diet and its evidence for effectiveness in cancer treatment concluded that there is no scientific evidence for the use of a macrobiotic diet in cancer treatment.
No current clinical trials are studying the role of the macrobiotic diet in cancer therapy. A ketogenic diet has been well established as an effective alternative treatment for some cases of epilepsy and has gained popularity for use in conjunction with standard treatments for glioblastoma.
The ketogenic diet can be difficult to follow and relies more on exact proportions of macronutrients typically a 4 to 1 ratio of fat to carbohydrates and protein than do other complementary and alternative medicine CAM diets. Because safety and feasibility have been proven, several trials are recruiting patients to study the effectiveness of the ketogenic diet on glioblastoma. Therefore, if a patient diagnosed with glioblastoma wishes to start a ketogenic diet, it would be safe if implemented properly and under the guidance of a registered dietitian,[ 10 ] but effectiveness for symptom and disease management remains unknown.
The use of probiotics has become prevalent within and outside of cancer therapy. Strong research has shown that probiotic supplementation during radiation therapy, chemotherapy, or both is well tolerated and can help prevent radiation- and chemotherapy-induced diarrhea, especially in those receiving radiation to the abdomen.
Melatonin is a hormone produced endogenously that has been used as a CAM supplement along with chemotherapy or radiation therapy for targeting tumor activity and for reducing treatment-related symptoms, primarily for solid tumors. Several studies have shown tumor response to, or disease control with, chemotherapy alongside oral melatonin, as opposed to chemotherapy alone; one study has shown tumor response with melatonin in conjunction with radiation therapy.
However, another study did not demonstrate increased survival with melatonin, but did demonstrate improved quality of life. Melatonin taken in conjunction with chemotherapy may help reduce or prevent some treatment-related side effects and toxicities that can delay treatment, reduce doses, and negatively affect quality of life.
Melatonin supplementation has been associated with significant reductions in neuropathy and neurotoxicity, myelosuppression, thrombocytopenia, cardiotoxicity, stomatitis, asthenia, and malaise. Overall, several small studies show some evidence supporting melatonin supplementation alongside chemotherapy, radiation therapy, or both for solid tumor treatment, for aiding tumor response and reducing toxicities, while negative side effects for melatonin supplementation have not been found.
Therefore, it may be appropriate to provide oral melatonin in conjunction with chemotherapy or radiation therapy to a patient with an advanced solid tumor.
Glutamine is an amino acid that is especially important for GI mucosal cells and their replication. These cells are often damaged by chemotherapy and radiation therapy, causing mucositis and diarrhea, which can lead to treatment delays and dose reductions and severely affect quality of life. Some evidence suggests that oral glutamine can reduce both of those toxicities by aiding in faster healing of the mucosal cells and entire GI tract.
For patients receiving chemotherapy who are at high risk of developing mucositis, either because of previous mucositis or having received known mucositis-causing chemotherapy, oral glutamine may reduce the severity and incidence of mucositis.
For patients receiving radiation therapy to the abdomen, oral glutamine may reduce the severity of diarrhea and can lead to fewer treatment delays. In addition to reducing GI toxicities, oral glutamine may also reduce peripheral neuropathy in patients receiving the chemotherapy agent paclitaxel.
Oral glutamine is a safe, simple, and relatively low-cost supplement that may reduce severe chemotherapy- and radiation-induced toxicities. The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above. Added Carneiro et al. Nutrition Screening and Assessment. Added Daniel et al. Added text to state that the prevalence of obesity is higher in adult cancer survivors than in those without a cancer history; and that cancer survivors with the highest rates of increasing obesity are colorectal and breast cancer survivors and non-Hispanic blacks cited Greenlee et al.
Added text about the benefits of using immune-enhancing formulas for preoperative and postoperative nutrition support for individuals undergoing gastrointestinal surgery cited Song et al.
Added Pharmaceutical management of cancer-associated cachexia and weight loss as a new subsection. This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about nutrition before, during, and after cancer treatment.
It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions. Board members review recently published articles each month to determine whether an article should:.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary. Any comments or questions about the summary content should be submitted to Cancer.
Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries. Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated.
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Deciding to Take Part in a Trial. Questions to Ask about Treatment Clinical Trials. Drugs Approved for Different Types of Cancer. Drugs Approved for Conditions Related to Cancer. Access to Experimental Drugs. Chronic disease—related malnutrition e. Acute disease—related or injury-related malnutrition e. Loss of muscle mass. Loss of subcutaneous fat. Localized or generalized fluid accumulation that may sometimes mask weight loss.
Diminished functional status as measured by hand grip strength. Screening Early recognition of nutrition-related issues is necessary for appropriate nutrition management of cancer patients. Education by registered dietitian or other clinician.
Intervention by registered dietitian. Critical need for improved symptom management. Food- and nutrition-related history. Biochemical data, medical tests, and procedures. Localized or generalized fluid accumulation. Diminished functional status e. Subcutaneous fat loss Orbit.
Thoracic and lumbar regions. Subcutaneous muscle loss Temple. Tumor location current or anticipated mechanical function impairment. Anticipated duration of symptoms. Eat foods that are high in protein and calories. Eat high-protein foods first in your meal while your appetite is strongest—foods such as beans, chicken, fish, meat, yogurt, and eggs. Add extra protein and calories to food. Cook with protein-fortified milk. Drink milkshakes, smoothies, juices, or soups if you do not feel like eating solid foods.
Prepare and store small portions of favorite foods. Seek foods that appeal to the sense of smell. Experiment with different foods. Eat larger meals when you feel well and are rested.
Sip only small amounts of liquids during meals. Eat your largest meal when you feel hungriest, whether at breakfast, lunch, or dinner. Be as active as possible to help develop a bigger appetite. Consider asking your health practitioner about blenderized drinks with a high nutrient density. Tell your doctor if you are having eating problems such as nausea, vomiting, or changes in how foods taste and smell.
Perform frequent mouth care to relieve symptoms and decrease aftertastes. Consider tube feedings if you are unable to sustain a certain amount of caloric intake to maintain strength. Drink plenty of fluids each day, including water, warm juices, and prune juice. Be active each day; take walks regularly. Eat more fiber-containing foods. Drink hot liquids to help relieve constipation, including coffee, tea, and warm milk. Talk with your doctor before taking laxatives, stool softeners, or any medicine to relieve constipation.
Limit certain foods if you develop gas, including broccoli, cabbage, cauliflower, beans, and cucumbers. Eat a large breakfast, including a hot drink and high-fiber foods. Consider a fiber supplement. Drink plenty of fluids to replace those lost from diarrhea, including water, ginger ale, and sports drinks. Let carbonated drinks lose their fizz before you drink them.
Eat foods and liquids that are high in sodium and potassium. Very hot or cold drinks. Greasy, fatty, and fried foods. Foods that can cause gas, such as carbonated beverages, cruciferous vegetables, legumes and lentils, and chewing gum. Milk products unless low lactose or lactose free. Sugar-free products sweetened with xylitol or sorbitol. Sip water throughout the day.
Have very sweet or tart foods and drinks — such as lemonade, to help make more saliva. Chew gum or suck on hard candy, ice pops, or ice chips; sugar free is best, but consult your doctor if you also have diarrhea.
Eat foods that are easy to swallow. Moisten food with sauce, gravy, or salad dressing. Do not drink any type of alcohol, beer, or wine. Avoid foods that can hurt your mouth, i. Keep your lips moist with lip balm. Rinse your mouth every 1 to 2 hours. Do not use mouthwash that contains alcohol. Do not use tobacco products, and avoid second-hand smoke. Talk with your doctor or dentist about artificial saliva or other products to coat, protect, and moisten your throat and mouth. Prepare your own low-lactose or lactose-free foods.
Choose lactose-free or low-lactose milk products. These products do not contain any lactose. Choose milk products that are low in lactose. Hard cheeses such as cheddar and yogurt are less likely to cause problems.
Try using lactase tablets when consuming dairy products. Lactase is an enzyme that breaks down lactose. Avoid only the milk products that give you problems. Try small portions of milk, yogurt, or cheese to see if you can tolerate them. Try calcium-fortified nondairy drinks and foods, which you can identify by food labels. Eat more calcium-rich vegetables, including broccoli and greens. Eat bland, soft, easy-to-digest foods rather than heavy meals.
Eat dry foods such as crackers, breadsticks, or toast throughout the day. Eat foods that are easy on your stomach: Avoid strong food and drink smells. Avoid eating in a room that has cooking odors or is overly warm; keep the living space comfortable but well ventilated. Sit up or recline with your head raised for 1 hour after eating.
Rinse your mouth before and after eating. As conceded early in the presentation, we are known to be able survive without exogenous glucose. If we could not supply our brain needs in this way, this would simply not be possible. That glucose is mostly synthesised out of protein, and the process is called gluconeogenesis.
This fact alone is enough to render this argument irrelevant, but there is more. In the situation for which no dietary glucose is provided, not only can we still make enough glucose endogenously to meet those needs, but in practice what happens is that our needs are different.
Instead of running primarily on glucose, our brains metabolism runs mostly on ketone bodies, and uses glucose for only a small portion of its needs, far less than our capacity to generate it.
Brand-Miller also insists that "The fetus grows on the mother's maternal blood glucose. However, she neglects to mention that fetuses make extensive use of ketones. I've covered infant brain growth and the importance of ketone bodies in this context several times, so I won't go into it here. See Babies thrive under a ketogenic metabolism , Meat is best for growing brains , What about the sugars in breast milk?
In any case, maternal blood glucose is maintained just fine without dietary sources, so even if babies did not use ketones, the point would be moot. Since our brain energy needs are met perfectly well with either a high glucose intake or a low glucose intake, it cannot be reasonable argued that our large brains must have developed under conditions of high glucose intake. There are still at this point two equally plausible evolutionary hypotheses that would enable the evolutionary development of large brains: An increase in both is also a plausible hypothesis, either together or in alternation.
For simplicity, let's start by considering one state or the other as being the predominant evolved state. Let's review what evolutionary circumstances would be required for each hypothesis, and what other circumstances would support it without being necessary. Then we can see what evidence we have for those circumstances. The reason we would need fat, and not just protein in the gluconeogenesis case, is that we are limited in our ability to metabolise protein.
Protein is better conceived of as a mainly a micronutrient, rather than a macronutrient, because of its structural importance. Besides water, our bodies are primarily made of amino acids and fatty acids. This is one reason why when we rely on gluconeogenesis for all of our glucose needs, we also have reduced glucose needs.
It spares protein for more important things. Protein availability is also of crucial importance even for the exogenous glucose hypothesis, because it is still a fundamental nutritional need outside of energy requirements.
Beyond protein, we would need to supply all of the nutrients that proper brain development requires. These include the minerals iodine, selenium, iron, zinc, vitamins B12, A, and D, and the vitamin-like choline, and the fatty acids DHA and arachadonic acid. Note that of the minerals listed here, animal sources are much more bioavailable, and that plant sources contain substances that actively interfere with absorption.
Of the vitamins and fatty acids, one B12 is not available even in precursor form, and the others only in precursor form. Humans are known to have low and variable ability to synthesise the necessary components out of precursors.
It is generally agreed upon in the scientific community that because of these hard requirements of the brain, a significant level of animal sourced food must have been part of our evolutionary heritage. This is supported by the absence of evidence of a single indigenous society that did not include some form of animal sourced food. The evidence for cooked tubers is weak at best. First, tubers in existence were seasonal and limited in supply.
Second, tubers in existence were highly fibrous, much more so than today's bred varieties, so they didn't yield much . The wild type still used by the Hadza, for example, have a low yield of glucose even when cooked. According to Schnorr, who studied this, "When roasted, they produce more energy, although the difference is not great. In the real world, the additional calorie content is probably lower than the cost of making a fire. Third, there is little evidence to support access to fire in the time period in question.
The most avid advocate of this theory, Wrangham whose book cover is featured on the slide , must resort to theorising that fire was available and widespread long before current evidence supports . His date estimates for use of fire were developed through backwards reasoning based on the assumption that starch was the evolutionary reason for our brains!
Since the only way would could have eaten starch was by cooking, and since our brains changed around 2 million years ago, Wrangham then infers that we must have had the use of fire at that time . While we cannot dispute the theory based on absence of evidence, it does remain theoretical, and is less probable given that we would expect to have found at least some such by now.
As to evidence for or against fruit and honey, this is an unlikely year round source of energy in the evolved environment, particularly during ice ages, and harvest time would not complement tubers. The so-called fruit based diet of other primates, is actually a fibre based diet, i.
That's because as in the case of tubers, wild fruits were mainly fibre. This points to the drastic difference in digestive systems between humans and our closest relatives. They clearly have extensive ability for hindgut fermentation, and we clearly do not.
If fruits were a major source of energy for humans, it would not have been the fibrous ones our primate cousins eat. There is no coherent continuity argument available from that perspective. In this scenario we would also still require animal sourced food for protein and other micronutrients, as discussed above.
Evidence for at least some hunted or scavenged game is well supported in various ways. We have direct evidence of hunting and scavenging going back long before evidence of fire, in the form of tools and bones.
Unlike in the case of tubers, cooking is not necessary to obtain nutrients and energy from meat and animal fat. Because of our protein and nutrient requirements, we would already have to be eating animal sourced food anyway, regardless of our source of energy. If the meat were lean, this would not by itself solve the energy problem. However, evidence suggests that the game available during the time in question was much fattier megafauna than modern leaner game . Insofar as this is true, it seems a stretch to suggest that early humans would have hunted game that met their protein and nutrient requirements, and then discarded an abundant energy source that came right along with it in favour of tubers.
Moreover, evidence suggests that our meat eating began with scavenging bones and skulls from other carnivorous kills, eating some scraps of meat, but primarily the marrow and high-fat brains we were able to crack our way into. In fact, the diversity of human diet after the extinction of the megafauna can be viewed as a variety of adaptations to the loss of our evolved diet, rather than evidence that we evolved to eat exactly like any one of them in particular.
This brings us to the supplemental arguments from Brand-Miller. It seems disingenuous to cite the Hadza, the society with the highest reported carbohydrate intake as evidence that we need carbohydrates to thrive. There are several known indigenous peoples or other groups that subsisted on very low exogenous carbohydrate levels before introduced to wheat and sugar.
The very existence of these societies contradicts the thesis. However, none of them, high carbohydrate or low, should be used as demonstration of a particular evolved way of eating.
They each show a way that is viable in the given environment. Carbohydrate can be used as a primary energy source and so can fat. But this is not enough to show which, if any, was primary during the time our brains evolved to make us anatomically modern. On average we have more copies of AMY1 than other primates. Brand-Miller claims that our number of copies of salivary amylase genes have changed because of our dietary intake of dietary carbohydrates.
This is a hypothesis. Fernandez and Wiley recently discussed several problematic inconsistencies in this hypothesis  , including the high variability in every population, the fact that starch digestion isn't materially affected by salivary amylase, and the existence of alternative possible functions of the gene.
I have touched on the apparent relationship to stress in a previous post Science Fiction. The hard-wired response to the taste of sweet is important and interesting, but I think it shows that sugar was rare, not a staple. Craving indicates a different kind of reward mechanism than one based on need. It is intensified by intermittent availability and scarcity. This is in stark contrast to protein and fat, both of which induce satiety. To me this indicates precisely that the environmental availability of sugar and starch was limited.
If it were unlimited, we would have had to develop internal responses to maintain homeostasis. As it is, it argues for seasonal gorge opportunities at best. The body has limited ability to store glucose. If glucose were the fuel of choice, it seems likely that we would have benefitted from expanded glycogen storage. Instead what we have is fat storage. We can afford to overeat sugar if we store it as fat, and then use the fat as fuel over time. The only way we can use fat as fuel is if we have stopped eating glucose for a significant period.
In contrast to other species we have studied, humans stay in ketosis even when they have substantially more protein than basic needs require. Like many species, in the absence of significant dietary carbohydrate, when our protein or caloric needs are not met, we produce ketones to spare protein and provide non-glucose energy, and we change our metabolisms to require less glucose.
Once protein is sufficient, though, other species will go back to the glucose based metabolism. Humans, apparently uniquely continue in ketogenic mode until and unless so much protein is ingested that the amount being metabolised is resulting in so much glucose that it has to be stored. This suggests that humans had an evolutionary timespan in which access to protein and fat was consistently high and carbohydrate was low for at least long periods.
I review the evidence for this here: Brand-Miller's evolutionary arguments that dietary carbohydrate was the fuel that allowed us to grow our large brains. The available evidence supports at best a seasonally alternating system of glucose and animal fat reliance for brain energy, and does not refute a long-term evolutionary adaptation for little and infrequent dietary glucose.
From the ape's dilemma to the weanling's dilemma: Epub Jan Some plant species, moreover, would require cooking to improve their digestibility and, despite claims to the contrary Wrangham et al. Other plant foods, such as the nut of the baobab Adansonia digitata , are high in protein, calories, and lipids and may have been exploited by hominoids in more open habitats Schoeninger et al. However, such foods would be too seasonal or too rare on any particular landscape to have contributed significantly and consistently to the diet of early hominins.
Moreover, while young baobab seeds are relatively soft and may be chewed, the hard, mature seeds require more processing. The Hadza pound these into flour Schoeninger et al. Meat, on the other hand, is relatively abundant and requires processing that was demonstrably within the technological capabilities of Plio-Pleistocene hominins.
Meat, particularly organ tissues, as Bogin , pointed out, would provide the ideal weaning food. Toward a Long Prehistory of Fire.
Michael Chazan Current Anthropology Following a discussion about what fire is and how it articulates with human society, I propose a potential scenario for the prehistory of fire, consisting of three major stages of development. From this perspective, obligate cooking developed gradually in the course of human evolution, with full obligate cooking emerging subsequent to modern humans rather than synchronous with the appearance of Homo erectus as envisioned by the cooking hypothesis.
From this observation, the logical inference is that obligate cooking must have a point of origin in hominin phylogeny. This point of origin is then mapped onto the increase in hominin brain and body size ca. The power of the approach taken by the cooking hypothesis is that it is at least partially testable based on experimental studies on the physiological and molecular correlates of consumption of cooked food see literature cited in Carmody et al.
However, this approach also has a number of shortcomings. First, while obligate cooking necessarily must have a point of phylogenetic origin, the same is not true for cooking that might become integrated into hominin adaptation through a process rather than as the result of a single event.
Second, while many aspects of human obligate cooking can be experimentally tested, there is no current method for testing whether H. In fact, the placement of the onset of obligate cooking at 2 million years ago is not directly testable without recourse to the archaeological record including recovery of residues from fossils; see Hardy et al. Rethinking the starch digestion hypothesis for AMY1 copy number variation in humans.
Am J Phys Anthropol. Existing claims for this function are based on the assumption that salivary a-amylase plays a crucial role in extracting glucose from plant foods. Specifically, it is assumed that glucose is a major product of a-amylase action, and disregard the essential rate-limiting action of maltase-glucoamylase and sucrase-isomaltase enzymes in whole starch hydrolysis. It may be that the early phase of starch digestion is important in some other way, or interacts in complex ways with these other brush border enzymes.
Thus, far there is no evidence that there has been selection on the genes for these other enzymes in humans. We show that a-amylase has alternative potential roles in humans, but find that there is insufficient evidence to fully evaluate their adaptive significance at present. AMY1 and AMY2 are widely distributed across diverse life forms; their ancient origin and conservation suggest that they play crucial roles in organismal fitness, but these are not well described, especially among mammals.
It could also be that higher AMY1 copies play no adaptive role, but have waxed and waned in copy number without strong selection favoring or disfavoring them.
In this regard, Iskow and colleagues indicate that although several examples of CNV at coding regions show signals of positive selection, it remains unclear whether these examples represent a pattern for CNV in humans. I recently had the honour to speak at Low Carb Breckenridge The video will be released publicly in the coming weeks, and when it does I will link to it here.
In the meantime, I'm posting my slides, notes and references. On a high carb diet, you might need to fast to attain an enlightened brain state. The only disclosure I have to declare is that I have some generous supporters on Patreon for my writing.
The supported content is free, so these are donations. The foundation of our biochemical understanding of ketosis came from experiments in fasted humans and other animals. For example the groundbreaking work of George Cahill. I recommend his publication Fuel Metabolism in Starvation [Cah] which reviews many of his findings. We continue to learn about mechanisms for how ketosis may increase health in a variety of ways.
However, these origins carry with them an implicit cautionary note, since starvation is generally not recommended, for obvious reasons. And it can do real harm, sometimes with lasting detrimental consequences. Even fasting for short periods is surrounded by controversy among experts at this very conference, because of its potential to do damage to lean mass, and all the potential problems of protein and calorie malnutrition. Many researchers conceptualise metabolism as operating in two complementary phases.
The act of eating or not eating sets off a cascade of hormonal and molecular signals that result in one phase or the other, Sometimes called the fed and fasting states. In this paper [Mat] they are called the glucose and ketone phases.
Important things happen in both phases. The fed state is attributed with generating and synthesising things like tissue, mitochondria, and neurons, But the fasted state is attributed with clearing broken structures for renewal and repair, and providing the stimuli to direct the synthesis phase.
Many believe that staying in either phase prolongedly leads to disease. And so you will hear people talk about metabolic switching, metabolic flexibility, insulin pulsatility, and so on.
Ketosis is normally an indication and a signal of the fasting state, so reason tells us that chronic long-term ketosis is unhealthy. So again, the comparison leads us to fear that ketosis may have benefits, but that it comes with a severe cost.
Insulin Signaling in the Central Nervous System. Daniel Porte, Denis G. Diabetes May , 54 5 ]. It turns out that starvation is not the only condition where ketosis naturally arises. Fetuses use ketones in the womb [Sha] , [Ada] , [Cun]. Breastfed infants are in mild ketosis [Per] , [Kra] , [Bou]. This graph shows how quickly the concentration of BOBH goes up in humans when they stop eating.
One of the stunning things about it is the orders of magnitude involved. Look for example at the year old children. If the 4-hour mark is about 0. In his presentation here, he has even said that benefits likely begin even below that level.
But they don't have to abstain from eating for ketosis to happen. For example, we have results in epileptic children. The previous standard had been a tightly protein restricted ketogenic diet. Eating a modified Atkins diet, which mostly just means they stay in the induction phase instead of adding back carbs, typically they are in ketosis, Even though they eat ad libitum [Kos].
Even adults have this ability. To know whether adults are able to stay in ketosis when protein needs are exceeded, we have to know what our protein needs are. It depends who you ask. I don't know of a study with the express purpose to find the upper bound of protein for ketosis, but we can look at studies that recorded it. Dogs can reach ketosis from fasting, but it takes longer, and never attains the same level [Cra]. I have spoken with staff at KetoPet Sanctuary , who treat cancerous dogs with ketosis.
They tell me that it is challenging to keep dogs in ketosis. They have to use a combination of protein restriction, calorie restriction, and MCT oils. It takes constant monitoring and adjustment. Rodents are often used in experimental conditions, and I do think they are very useful models, but it takes more protein or calorie restriction to achieve an appropriate degree of ketosis than it would with humans. Similarly, almost any level of dietary carbohydrates is enough to shut down ketosis [Richard David Feinman, personal communication].
Some researchers believe this has to do with their relative lack of brains, Since ketosis has been thought of as a way to spare glucose for the brain. In fact they are specialised at gluconeogenesis, that is, getting all their energy needs met by converting protein into glucose.
Protein needs tend to be high. Dolphins are particularly interesting because they have really large brains, and they eat a diet that would be expected to be ketogenic if fed to humans. Instead, they ramp up gluconeogenesis [Rid]. When faced with this observation that humans use ketosis even when they don't have to for glucose production, one obviously wonders how this happens from a mechanistic standpoint.
I have never seen the question raised in the literature, let alone answered. If I were to take a guess, I'd say it probably happens somewhere in this process. CPT1A is a kind of gatekeeper, transporting fatty acids into the mitochondria for oxidation. This is normally a necessary step in the creation of ketone bodies. The functional reason it does that is because malonyl-CoA is a direct result of glucose oxidation and is on the path to de novo lipogenesis. It could be inefficient to be both generating fat and oxidizing it.
So this is a convenient signal to slow entry of fat into the mitochondria. However, its action is not stictly linear. Hysteresis is a way of preventing thrashing back and forth between two states at the threshold of their switch.
This would result in constant switching. Instead, a thermostat waits until the temperature drops a little lower before activating the heater, and heats it a little more than required before deactivating it.
That means that fluxuations in glucose oxidation, or small, transient increases in glucose oxidation don't disturb the burning of fatty acids or the production of ketones.
It could be the case that humans develop more insensitivity to malonyl-CoA under ketosis than other species do, allowing them to metabolise more protein without disturbing ketosis. That mutation slows down CPT1A activity immensely. This was permitted by their diet which was very high in polyunsaturated fats from sea mammals. Polyunsaturated fats upregulate fatty acid oxidation by a large proportion compared to saturated fats [Cun] , [Fra] , [Fue] , so this mutation would not necessarily have been disruptive of ketosis in that population when eating their natural diet [Lem].
That means they are less likely to be knocked out of ketosis by high protein intake. I will go into this in much greater detail in my upcoming talk at AHS The second question that comes to mind is what does this difference imply about our evolutionary environment?
I would suggest that for humans to have developed the ability to stay in ketosis even with more than sufficient protein intake, we must have at least have spent frequent long periods in a condition of very low carbohydrate, high fat access, either exogenously or endogenously, and more than adequate protein as a dietary norm. Why do we stay in ketosis even when we have enough protein to feed the brain glucose without compromising lean mass.
Or to put it another way: Other animals continue to burn through lean mass with or without ketosis until they have enough protein to fuel everything with glucose. I suspect it has something to do with our brains. Optimal Weaning from an Evolutionary Perspective. Our brains are big. Primates are already big brained for mammals, and from that starting point our brains tripled in size over the course of a couple million years.
Herbivores get most of their energy from fibre by fermenting it in the gut. So we transferred to a strategy of eating fat directly Giving up colon size for brain size. To get enough fat directly, we had to eat meat. But the rest can be met by ketones. Our brains use ketones preferentially when they are available. This may explain why human babies are so fat. These graphs are from a paper exploring different hypotheses about baby fat [Kuz] , one of them being to supply the brain energy in the form of ketones.
The one on the right is what percent of oxygen metabolised by the whole body is going to the brain: Another consideration is building materials, since our brains are made mostly of fat and cholesterol and we know that ketones are used to synthesize those in situ. The diagram here [Cot] shows pathways of how ketones can be generated, oxidized, or used to make fat and cholesterol.
Fetuses and newborns use ketone bodies extensively, as I mentioned previously. In light of that, It seems like a reasonable hypothesis that ketogenic capacity in humans is so pronounced in childhood because the brain is developing, And ketones are for some reason the preferred material. Other species tend to wean at the time when brain growth stops. That means that for them ketogenesis stops at the same time brain growth stops. Even after it reaches about full size in adolescence, it continues to change structurally well into adulthood.
However, quantitatively, this structural cost is very small compared to energy considerations [Kuz] , And so that hypothesis seems relatively weak on its own. Another set of ideas comes from the metabolic effects we see in the lab and clinic. These are just a few metabolic changes relative to a high carb diet. Each can have profound effects on the workings of the brain. I do want to draw attention to the last one about availability of arachadonic acid and DHA.
These are important for the brain as they make up the phospholipids, and they are subject to a lot of turnover. Each of these effects has been proposed as a solution to the mystery of why a ketogenic diet treats epilepsy so effectively [Bou] , [Nyl] , [Mas] , [deL]. Epilepsy is just the condition with the most research, and the widest acknowledgment.
Other conditions for which at least some evidence supports improvement via a ketogenic diet include neurological disabilities in cognition and motor control [Sta] ; the benefit here may have to do with the proper maintenance of brain structures such as myelination Recall phases: Survival after brain damage, the hypoxia of stroke or blows to the head is improved in animal models [Sta].
There is even animal evidence that brain damage due to nerve gas is largely mitigated by being in a state of ketosis during the insult [Lan].
Again, this suggests a structural support and resilience provided by a ketogenic metabolism. Resilience comes in part from not being as susceptible to damage in the first place, and that could be from reduced oxidative stress when using ketones for fuel. Ketogenic diets as a treatment for cancer are controversial, but some of the best evidence in support of it comes from glioblastomas.