The ketogenic diet has numerous metabolic effects. However, there are numerous other metabolic effects that need to be discussed as well as concerns which are typically raised regarding the ketogenic diet. This document examines the effects (and side-effects) of the metabolic state of ketosis on the human body. As well, some of the major health concerns which have been voiced regarding the ketogenic diet are addressed here. There are ultimately two main concerns regarding the ketogenic diet in terms of health risks. The first is the potential negative effects of the ‘high protein’ intake of the ketogenic diet. Additionally, there is the effect of high levels of ketones. They are discussed as needed below. Please note that not all of the effects of ketosis on human physiology are known at this time. Ketosis has been studied for almost 100 years and will most likely continue to be studied so any information provided here represents only the current base of knowledge. For this discussion, no distinction is made, except as necessary, between starvation ketosis and dietary ketosis.
A note on long-term effects
There are few studies of the long-term effects of a ketogenic diet. One of the few, which followed two explorers over a period of 1 year was done almost 70 years ago (1). Beyond that study, the two models most often used to examine the effects of the ketogenic diet are the Inuit and pediatric epilepsy patients. Epileptic children have been studied extensively, and are kept in ketosis for periods up to three years. In this group, the major side effects of the ketogenic diet are elevated blood lipids, constipation, water-soluble vitamin deficiency, increased incidence of kidney stones, growth inhibition, and acidosis during illness. However, the pediatric epilepsy diet is not identical the typical ketogenic diet used by dieters and healthy adults, especially in terms of protein intake, and may not provide a perfect model. While studies of epileptic children give some insight into possible long term effects of a ketogenic diet, it should be noted that there are no studies of the long-term effects of a CKD or similar diet approach. The consequences of alternating between a ketogenic and non-ketogenic metabolism are a total unknown. For this reason, it is not recommended that a CKD, or any ketogenic diet, be followed indefinitely.
Insulin resistance
Although low-carbohydrate diets tend to normalize insulin and blood glucose levels in many individuals, a little known effect is increased insulin resistance when carbohydrates are refed. There is little research concerning the physiological effects of refeeding carbohydrates after long-term ketogenic dieting although fasting has been studied to some degree. Early ketogenic diet literature mentions a condition called ‘alloxan’ or ‘starvation diabetes’, referring to an initial insulin resistance when carbohydrates are reintroduced to the diet following carbohydrate restriction (2). In brief, the initial physiological response to carbohydrate refeeding looks similar to what is seen in Type II diabetics, namely blood sugar swings and hyperinsulinemia. This type of response is also seen in individuals on a CKD. It should be noted that this response did not occur universally in research, being more prevalent in those who had preexisting glucose control problems. As well, exercise appears to affect how well or poorly the body handles carbohydrates during refeeding. One hypothesis for this effect was that ketones themselves interfered with insulin binding and glucose utilization but this was shown not to be the case (3,4). In fact, ketones may actually improve insulin binding (2). The exact reason for this ‘insulin resistance’ was not determined until much later. The change was ultimately found to be caused by changes in enzyme levels, especially in those enzymes involved in both fat and carbohydrate burning (5). High levels of free fatty acid levels also affect glucose transport and utilization (6). Long periods of time without carbohydrate consumption leads to a down regulation in the enzymes responsible for carbohydrate burning. Additionally, high levels of free fatty acids in the bloodstream may impair glucose transport (6). This change occurs both in the liver (5) and in the muscle (5,7). During carbohydrate refeeding, the body upregulates levels of these enzymes but there is a delay during which the body may have difficulty storing and utilizing dietary carbohydrates. This delay is approximately 5 hours to upregulate liver enzyme levels and anywhere from 24-48 hours in muscle tissue (8,9). While there is a decrease in carbohydrate oxidation in the muscle, this is accompanied by an increase in glycogen storage (7). These time courses for enzyme up-regulation correspond well with what is often seen in individuals on a CKD, which is really nothing more than a ketogenic diet followed by carbohydrate refeeding done on a weekly basis. Frequently, individuals will report the presence of urinary ketones during the first few hours of their carb-loading period, seeming to contradict the idea that carbohydrates always interrupt ketosis. This suggests that the liver is continuing to oxidize fat at an accelerated rate and that ingested carbohydrates are essentially not being ‘recognized’ by the liver. After approximately 5 hours, when liver enzymes upregulate, urinary ketone levels typically decrease as liver glycogen begins to refill. Another interesting aspect of carbohydrate refeeding is that liver glycogen is not initially refilled by incoming glucose. Rather glucose is released into the bloodstream for muscle glycogen resynthesis (especially if muscle glycogen stores are depleted) initially, refilling liver glycogen later. In practice, many individuals report what appears to be rebound hypoglycemia (low blood sugar) either during the carb-up or during the first few days of eating carbohydrates when ketogenic eating is ended, for the reasons discussed above. Ketones themselves do not appear to alter how cells respond to insulin (4) which goes against the popular belief that ketogenic diets somehow alter fat cells, making them more likely to store fat when the ketogenic diet is ended. Practical experience shows this to be true, as many individuals have little trouble maintaining their bodyfat levels when the ketogenic diet is stopped, especially if their activity patterns are maintained.
Appetite suppression
An unusual effect of complete fasting is a general decrease in appetite after a short period of time. Additionally, studies which restrict carbohydrate but allow ‘unlimited’ fat and protein find that calorie intake goes down compared to normal levels further suggesting a link between and appetite (10,11). Since continued fasting causes an increase in ketone bodies in the bloodstream, achieving a maximum in 2-3 weeks, it was always assumed that ketones were the cause of the appetite suppression (12). As with many aspects of ketosis (in this case starvation ketosis), this assumption was never directly studied and propagated itself through the literature without challenge. Recent research indicates that ketones per se are most likely not the cause of the decreased appetite during ketosis. As discussed in chapter 9, several studies have shown an automatic decrease in caloric intake (and presumably appetite) when individuals restrict carbohydrates to low levels, despite being told to eat ‘unlimited’ amounts of fat and protein. In one study the ketogenic diet suppressed appetite more so than a balanced diet where an appetite suppressant was given (13). Several studies have compared appetite on a very low calorie (below 800 calories/day) ketogenic diet versus appetite on a balanced diet with the same calories (14,15). In general, no difference was seen in appetite between the two diets. This leads researchers to think that ketones do not blunt appetite in and of themselves. Rather two possible mechanisms seem a more likely explanation for the appetite blunting seen with a ketogenic diet. First, is the relatively higher fat content of the ketogenic diet compared to other diets. Fat tends to slow digestion, meaning that food stays in the stomach longer, providing a sense of fullness. The same has been shown to for protein (14). Additionally, protein stimulates the release of the hormone cholecystokinin (CCK) which is thought to help regulate appetite. However, studies using very-low-calorie intake (and hence low dietary fat intakes) have documented this same blunting of appetite, suggesting a different mechanism. Rather than the effects of dietary fat, the researchers argue that what is perceived as a blunting of appetite is simply a return to baseline hunger levels. That is, during the initial stages of a diet, there is an increase in appetite, which is followed by a decrease over time. It is this decrease which is being interpreted by dieter’s as a blunting of appetite (14,15). Overall, the data supporting an appetite suppressing effect of ketogenic diets points to a mechanism other than ketones. This is not to say that appetite may not be suppressed on a ketogenic diet, only that it is most likely not ketones or metabolic ketosis which are the cause of the suppression. Anecdotally, some individuals have a strong suppression of appetite while others do not. This discrepancy can probably be ascribed to individual differences. If a dieter’s appetite is suppressed substantially on a ketogenic diet, it may be difficult for them to consume the 73 necessary calories. In this case, the use of calorically dense foods such as mayonnaise and vegetable oils can be used to increase caloric intake. If appetite is not suppressed on a ketogenic diet, less calorically dense foods can be consumed.
Cholesterol levels
The relatively high fat intake of the ketogenic diet immediately raises concerns regarding the effects on blood lipids and the potential for increases in the risk for heart disease, stroke, etc. Several key players in relative risk for these diseases are low density lipoproteins (LDL, or ‘bad cholesterol’), high density lipoproteins (HDL, or ‘good cholesterol’) and blood triglyceride levels (TG). High levels of total cholesterol, and high levels of LDL correlate with increased disease risk. High levels of HDL are thought to exert a protective effect against cholesterol-related disease. The overall effects of implementing a ketogenic diet on blood cholesterol levels are far from established. Early short-term studies showed a large increase in blood lipid levels (16,17). However, later studies have shown either no change or a decrease in cholesterol levels (18-20). One problem is that few long term studies are available on the ketogenic diet, except in epileptic children. In this population, who are kept in deep ketosis for periods up to three years, blood lipid levels do increase (21,22). However, the ketogenic diet is not thought to be atherogenic due to the fact that any negative effects induced by three years in ketosis will be corrected when the diet is ended (22). It has been shown that Inuits, who maintain a ketogenic diet for long periods of time every year, do not develop heart disease as quickly as other Americans (23), suggesting that there are no long term effects. However, this may be related to the fact that a ketogenic diet is not continued indefinitely. There may be a slow removal of cholesterol from the arteries during time periods when a more balanced diet is being followed (23). Most of the degenerative diseases thought to be linked to high blood lipid levels take years (or decades) to develop. Unless an individual is going to stay on a ketogenic diet for extremely long periods of time, it is not thought that there will be appreciable problems with cholesterol buildup. From a purely anecdotal standpoint, some individuals who have undergone testing show a complete lack of cholesterol buildup in their arteries. Another problem is that weight/fat loss per se is known to decrease cholesterol levels and it is difficult to distinguish the effects of the ketogenic diet from the effects of the weight/fat loss which occurs. A few well-designed studies allow us to make the following rough generalizations:
- If an individual loses weight/fat on a ketogenic diet, their cholesterol levels will go down (18,24,25);
- If an individual does not lose weight/fat on a ketogenic diet, their cholesterol levels will go up (24,26)
As well, there can be a decrease followed by increase in blood lipid levels (27). This is thought to represent the fact that body fat is a storehouse for cholesterol and the breakdown of bodyfat during weight loss causes a release of cholesterol into the bloodstream (27). Additionally, women may see a greater increase in cholesterol than men while on the ketogenic diet although the reason for this gender difference in unknown (28). In practical experience however, there is a great range of responses among individuals on a ketogenic diet. Some show a drastic decrease in cholesterol while others shown an increase. Changes in blood TG levels are also common on the ketogenic diet. Somewhat counter-intiuitively, there is generally a decrease in blood TG levels, (28) which may indicate greater uptake of TG by tissues such as skeletal muscle. Since no absolute conclusions can be drawn regarding cholesterol levels on a ketogenic diet, dieters are encouraged to have their blood lipid levels monitored for any negative responses. Ideally, blood lipid levels should be checked prior to starting the diet and again 6-8 weeks later. If repeat blood lipid tests show a worsening of lipid levels, saturated fats should be substituted with unsaturated fats or the diet should be abandoned.
Low energy levels
Carbohydrates are the body’s preferred fuel when they are available (see chapter 4). As well, they burn more efficiently than fats. Many individuals voice concerns about drops in general energy levels (not including exercise) on a ketogenic diet due to the lack of carbohydrates. Many subjects in early studies on ketosis or the PSMF noted transient lethargy and weakness. As well many studies noted a high occurrence of orthostatic hypotension which is a drop in blood pressure when individuals move from a sitting to standing position. This caused lightheadedness in many individuals. It was always taken for granted that ketosis caused this to happen. However, later studies established that most of these symptoms could be avoided by providing enough supplemental minerals, especially sodium. Providing 4-5 grams of sodium per day (not much higher than the average American diet) prevents the majority of symptoms of weakness and low energy, possibly by maintaining normal blood pressure (26). In most individuals fatigue should disappear within a few days to a few weeks at most. If fatigue remains after this time period, small amounts of carbohydrates can be added to the diet, as long as ketosis is maintained, or the diet should be abandoned for a more balanced diet. To summarize, ketogenic diets can generally sustain low-intensity aerobic exercise without problem after a period of adaptation. However, because carbohydrates are an absolute requirement to sustain high intensity exercise such as weight training or high-intensity aerobic exercise, a standard ketogenic diet is not appropriate.
Effects on the brain
A well-known effect of ketogenic diets is the increased use of ketones by the brain (29). As well, some of the effects of the ketogenic diet in treating childhood epilepsy may be due to this increased extraction of ketones (30,31). Due to the changes which occur, a variety of concerns has been voiced in terms of possible side-effects. These include permanent brain impairment and short-term memory loss. These concerns are difficult to understand in terms of where they originated. What must be understood is that ketones are normal physiological substances. Ketones provide the brain with fuel when glucose (or food in general) is not available. The brain develops the enzymes to use ketones during fetal development and these enzymes are still present as we age (32), which should serve to illustrate that ketones are normal fuels, and not toxic byproducts of an abnormal metabolism. Although not a perfect model, epileptic children provide some insight into possible detrimental long term effects of the ketogenic diet on brain function. Quite simply, there are no negative effects in terms of cognitive function (30). Except for some initial transient fatigue, similar to what is reported in adults, there appears to be no decrement in mental functioning while on the diet or after it is ended. However, this is not absolute proof that the ketogenic diet couldn’t have possible long-term effects on the brain; simply that no data currently exists to suggest that it will have any negative effects. Anecdotally, individuals tend to report one of two types of functioning while in ketosis: excellent or terrible. Some individuals feel that they concentrate better and think more lucidly while in ketosis; others feel nothing but fatigue. Differences in individual physiology may explain the difference. With regard to short term memory loss, the only study which remotely addresses this point is a recent study which showed temporary decrements in a trail-making task (which requires a high degree of mental flexibility) during the first week of a low-calorie ketogenic diet as compared to a non-ketogenic diet (33). The majority of the effects were seen during the first week of the diet, and disappeared as the study progressed. As stated previously, some individuals do note mental fatigue and a lack of concentration during the first 1-3 weeks of a ketogenic diet. In practical terms, this means that individuals who operate heavy machinery, or need maximum mental acuity for some reason (i.e. a presentation or final exam) should not start a ketogenic diet during this time period.
Uric acid levels
Uric acid is a waste product of protein metabolism that is excreted through the kidneys. Under normal circumstances, uric acid is excreted as quickly as it is produced. This prevents a buildup of uric acid in the bloodstream which can cause problems, the most common of which is gout. Gout occurs when urate cause deposit in the joints and cause pain. High levels of uric acid in the bloodstream can occur under one of two conditions: when production is increased or when removal through the kidneys is decreased. The ketogenic diet has been shown to affect the rate of uric acid excretion through the kidneys. Ketones and uric acid compete for the same transport mechanism in the kidneys. Thus when the kidneys remove excess ketone bodies from the bloodstream, the removal of uric acid decreases and a buildup occurs. Studies of the ketogenic diet and PSMF show a consistent and large (oftentimes doubling or tripling from normal levels) initial increase in uric acid levels in the blood (24,26). In general however, levels return towards normal after several weeks of the diet (35). Small amounts of carbohydrates (5% of total daily calories) can prevent a buildup of uric acid (35). Additionally, in studies of both epileptic children as well as adults the incidence of gout are very few, and only occur in individuals who are predisposed genetically (12, 26,34). Related to this topic, uric acid stones have occasionally been found in epileptic children following the ketogenic diet (36). This appears to be related to high levels of urinary ketones, low urinary pH and fluid restriction in these patients. It is unknown whether individuals consuming sufficient water on a ketogenic diet have any risk for this complication. From a practical standpoint, individuals with a genetic predisposition towards gout should either include a minimal amount of carbohydrates (5% of total calories) in their diet or not use a ketogenic diet.
Kidney stones and kidney damage
A common concern voiced about ketogenic diets is the potential for kidney damage or the passing of kidney stones, presumably from an increase in kidney workload from having to filter ketones, urea, and ammonia. As well, dehydration can cause kidney stones in predisposed individuals. Finally, the ‘high-protein’ nature of ketogenic diets alarms some individuals who are concerned with potential kidney damage. Overall there is little data to suggest any negative effect of ketogenic diets on kidney function or the incidence of kidney stones. In epileptic children, there is a low incidence (~5%) of small kidney stones (22,30). This may be related to the dehydrated state the children are deliberately kept in rather than the state of ketosis itself (22). The few short-term studies of adults suggest no alteration in kidney function (by measuring the levels of various kidney enzymes) or increased incidence of kidney stones, either while on the diet or for periods up to six months after the diet is stopped (26). Once again, the lack of any long-term data prevents conclusions about potential long-term effects of ketosis on kidney function. With regards to the protein issue, it should be noted that kidney problems resulting from a high protein intake have only been noted in individuals with preexisting kidney problems, and little human data exists to suggest that a high protein intake will cause kidney damage (37). From a purely anecdotal standpoint, athletes have consumed high protein diets for long periods and one would expect kidney problems to show up with increasing incidence in this group. But such an increase has not appeared, suggesting that a high protein intake is not harmful to the kidneys under normal circumstances (37). However, much of this is predicated on drinking sufficient water to maintain hydration, especially to limit the possibility of kidney stones. Individuals who are predisposed to kidney stones (or have preexisting kidney problems) should consider seriously whether a ketogenic diet is appropriate for them. If they do choose to use a ketogenic diet, kidney function should be monitored with regular blood work to ensure that no complications arise.
Liver damage
Another concern often raised is for the potential negative effects of a ketogenic diet on the liver. In one of the few longer-term (4 weeks) studies of the ketogenic diet, liver enzymes were measured and no change was observed (26). Additionally, no liver problems are encountered in epileptic children. However, it is unknown whether negative effects would be seen in the longer term.
Constipation
Arguably one of the more common side-effects seen on a ketogenic diet is that of reduced bowel movements and constipation (30,34). In all likelihood, this stems from two different causes: a lack of fiber and increased gastrointestinal absorption of foods. First and foremost, the lack of carbohydrates in a ketogenic diet means that fiber intake will be low unless supplements are used. There is no doubt that fiber is a important nutrient to human health. A high fiber intake has been linked to the prevention of a variety of health problems including some forms of cancer and heart disease. To make a ketogenic diet as healthy as possible, some type of sugar-free fiber supplement should be used. In addition to possibly preventing any health problems, this will help to maintain bowel regularity. Many individuals find that a large salad containing fibrous vegetables may help with regularity and should fit easily with the 30 gram carbohydrate limit. One interesting effect of the ketogenic diet is the typically reduced stool volume seen (30). Presumably this is due to enhanced absorption/digestion of foods which leads to less waste products being generated (22).
Vitamin/mineral deficiencies
The restricted food choices of a ketogenic diet raise concerns about possible deficiencies in vitamin and mineral intake. Any diet which is restricted in calories, whether ketogenic or not, will show a decrease in micro-nutrient intake compared to a similar diet at higher calories. So, the question is whether the ketogenic diet is more or less nutritionally adequate compared to a ‘balanced’ diet at the same calorie level. While this is a fairly moot point for those who have already decided to use a ketogenic diet, it is important to examine, if for no other reason than to know what nutrients should be supplemented to the diet. It is difficult, if not impossible, to obtain adequate micro-nutrients on any diet containing less than 1200 calories per day (37). To a great degree, micro-nutrient intake is affected by total caloric intake regardless of diet. That is, a diet containing 400 calories will have less micronutrients that one containing 2000 calories regardless of composition. Therefore, let us look at nutrient intake relative to caloric intake (amount of nutrient per calorie). One researcher did exactly this, comparing nutrient intakes of his low-carbohydrate diet to the subject’s normal diet (39). He then examined how much micronutrient intake would be affected if the subject’s normal diets were reduced to the same caloric level as they consumed on the low-carbohydrate diet. As these studies demonstrated, there will obviously be a decrease in nutrient intake if a subject decreases caloric intake from 1900 to 1400 (39). The question therefore is whether a 1400 calorie ketogenic diet is more or less nutritionally complete than a 1400 calorie balanced diet. On an absolute level, small decreases in thiamine, nicotinic acid, calcium and iron were noted while there were increases in vitamin D and riboflavin. When compared on a relative scale (amount of nutrient per 1000 calories), nutrient intake was actually higher on the low carbohydrate diet (39). It should be noted that the diet studied was higher in carbohydrate (averaging 67 grams per day) than most ketogenic diets and contained milk. This provides only a limited model for a diet containing 30 grams of carbohydrate or less per day. Another study examining nutrient intake of a ketogenic diet at 2100 calories found the ketogenic diet to provide greater than the RDA for Vitamin A, Vitamin C, riboflavin, niacin, and phosphorous. There were deficiencies in thiamine, Vitamin B-6, folacin, calcium, magnesium, iron, zinc and fiber (38). It should be noted that current research into optimal health and prevention of diseases focuses on nutrients in vegetables called phytonutrients, which appear to play a protective role in many diseases. The limited vegetable intake on a ketogenic diet means that these nutrients will not be consumed to any appreciable degree. This once again points to the fact that the ketogenic diet should probably not be used long term (unless indicated for medical reasons), or that individuals on a ketogenic diet should use their small carbohydrate allowance to maximize vegetable intake. Due to its restrictive nature, the ketogenic diet can be deficient in certain nutrients. However, this is no different than any other calorically restricted diet in that any reduction in food intake will result in a reduction in nutrient intake. At the very minimum, a basic multivitamin/mineral (providing at least the RDA for all nutrients) should be taken daily to avoid deficiencies. Depending on the intake of dairy foods such as cheese, a calcium supplement may be warranted. Specific nutrients, especially electrolytes are discussed in the next section.
Electrolyte excretion/Death
The diuretic (dehydrating) nature of ketosis causes an excretion of three of the body’s primary electrolytes: sodium, potassium, and magnesium (31,40). These three minerals are involved in many processes in the body, one of which is the regulation of muscle contraction, including the heart. Some studies show a net loss of calcium while others do not (31). A severe loss of electrolytes is problematic. At the least, it can cause muscle cramping, which is often reported by individuals on a ketogenic diet. At the extreme, it can compromise normal heart function. During the late 1970’s, a large number of deaths occurred in individuals following a 300 calorie per day liquid ketogenic diet called “The Last Chance Diet” (41-43). This diet relied on a processed protein as its only source of calories and the protein, which was a hydrolyzed collagen protein with the amino acid tryptophan added to it, contained no vitamins or minerals. As well, mineral supplements were not given or suggested to individuals on the diet. Several possible causes for these deaths have been suggested, including the direct breakdown of the heart due to the low quality of protein used (42). A second, and more likely cause was that the depletion of electrolytes caused fatal heart arrhythmias. As well, given high quality protein and adequate mineral supplementation, no cardiac abnormalities appear in individuals on a ketogenic diet (44). “The Last Chance Diet” should be contrasted to a ketogenic diet based around whole foods. The intake of whole protein foods will ensure some intake of the three electrolytes. Even so, studies show that the amount of electrolytes consumed by most on a ketogenic diet is insufficient. Some of the fatigue which was demonstrated in early ketogenic diet studies may have occurred from insufficient mineral intake, especially sodium (26). A known effect of ketogenic diets is a decrease in blood pressure, most likely due to sodium excretion and water loss. In individuals with high blood pressure (hypertension), this may be beneficial. Individuals with normal blood pressure may suffer from ‘orthostatic hypotension’ which is lightheadedness which occurs when moving from a sitting to standing posture (45). The inclusion of sufficient minerals appears to be able to prevent symptoms of fatigue, nausea and hypotension (26). To counteract the excretion of minerals on a ketogenic diet, additional mineral intake is required. Although exact amounts most vary, suggested amounts for the three primary electrolytes appear below (26,46):
- Sodium: 3-5 grams in addition to the sodium which occurs in food
- Potassium: 1 gram in addition to the 1-1.5 grams of potassium which occur in food
- Magnesium: 300 mg
Note: An excessive intake of any single mineral (especially potassium) can be just as dangerous as a deficiency. Although the values listed above are averages, individuals are encouraged to have mineral levels checked to determine the required level of mineral supplementation. At no time should mineral supplements be taken in excess.
Calcium loss/Osteoporosis
A general belief states that high protein diets may be a causative factor in osteoporosis but this is still highly debated (47,48). While studies have shown increased calcium excretion with high protein intakes, this was typically with ‘purified’ proteins (37). It is thought that wholefood proteins do not cause this to occur as the high phosphate content prevents calcium losses (37). In any event, the ‘high protein’ nature of the ketogenic diet raises concerns about calcium loss and osteoporosis. There is some evidence that the ketogenic diet causes disordered calcium metabolism, especially if it is combined with drug treatment for epilepsy (49). This effect is reversed when adequate Vitamin D is consumed. Additionally, depending on dairy intake, a calcium supplement may be necessary to ensure positive calcium balance. The current guidelines for calcium intake are 1200 milligrams/day for men and pre-menopausal women and 1500 mg/day for post-menopausal women.
Weight/Fat regain
It is well known that dieting alone shows extremely poor rates of long-term success. Typically, less than 5-10% of individuals who lose weight through dieting alone will maintain that weight loss in the long term. In brief, any fat loss efforts based on caloric restriction alone are typically bound for failure, regardless of whether the diet used is ketogenic or not. For some reason, there is a concern that weight regain is more of an issue on ketogenic diets than other diets. This most likely stems from the confusion between the loss of body weight and the loss of bodyfat. The dehydration and glycogen depletion, which occurs on ketogenic diets can be anywhere from 1 to 15 pounds of bodyweight. Thus, it is to be expected that this weight will be regained when carbohydrates are reintroduced into the diet (either because the diet is being stopped, or for carb-ups as with a CKD). For individuals who fixate on the scale as the only measure of their progress, this weight regain can be disheartening and may make the individual fear carbohydrates as the source of their excess body weight. Dieters must realize that the initial weight gain is water and glycogen (carbohydrate stored in the muscle) and move past it. Focusing on changes in body composition should avoid psychological problems with the weight regain from replenishing water and glycogen.
Immune system
Anecdotally, there is a great deal of variety in individual response to ketogenic diets in terms of the immune system. Some individuals have reported a decrease in certain ailments, notably allergy symptoms, while others become more susceptible to minor sicknesses. There is limited research into the effects of a ketogenic diet on the immune system with two studies showing decrements in some indices of immune system status (50,51). However, one of these studies (50) was done on epileptic children who may consume inadequate protein while the other was done during a PSMF (51). Therefore, it is difficult to be sure whether it is ketosis, a lack of protein, or a lack of calories which is causing these decrements in immune system status. Since no decrease in immune system status was seen when a maintenance calorie ketogenic diet was given, (26) it would seem that any negative immune systems effects in the other studies were caused by low calories and inadequate protein.
Optic neuropathy
One unusual side effect of ketogenic diets which has appeared in a few cases is the development of optic neuropathy, which is a dysfunction of the optic nerve. In all cases, the problem was linked to the fact that the individuals in question were not receiving calcium or vitamin supplements for periods of up to a year. Supplementation of adequate B-vitamins, especially thiamine, corrected all cases which were reported (52,53).
Hair loss/changes in finger and toenails
A final effect which has occasionally been noted, primarily during total fasting or the PSMF, is transient hair loss (34). In a related vein, some individuals have reported changes in the quality of their finger and toe nails. The cause of this phenomenon is unknown but could possible be related to protein or vitamin and mineral intake.