Everything in life has side-effects. Some are good and some are bad. Sometimes it is the lesser of two evils that we must choose. High carbohydrate diets have side-effects such as heart disease, diabetes, aging, hyperinsulinemia, raised cholesterol and weight gain. Everything we put into our body from water to drugs to food has side-effects. In the case of water, they are generally good side-effects.

Now before anyone freaks out about what I’m about to post, remember where the above side-effects of a pattern of high carbohydrate intake has taken you. And if you have ever taken Fen-Phen or Meridia or Fastin or Ephedra or caffeine or anything else to lose weight, you should consider the side-effects of those drugs and chemicals as worse than the side-effects of ketosis.

Remember that all this information is due to my diligence in wanting to know what is going on in my body during a low-carbohydrate ketogenic diet. I’m the type who reads all the side-effects on all drug medications I’ve taken in my life and who reads the fine print on medical documents that I sign. Most people would be too frightened to take any drug or have any surgical operation performed on them if they did this. So if you are that type of person, forget reading this. Know that most research has shown and I quote: “Most adverse effects were mild, self-limited, and occurred early.”

Now for those who want to know the worst and best and how to mitigate side-effects, read on.

To make this easy reading I’m going to list what I’ve learned so far and then present the data. As I learn more, I’ll update this post.

There haven’t been a lot of studies done on the effects of ketogenic diets for weight loss, but there have been plenty of studies regarding ketogenic diets for control of epilepsy. Some of these studies were done on non-epileptic rats and mice. Rats and mice are exceptionally good research animals due to the fact that their endocrine system is very similar to humans. Some side-effects come from smaller studies where percentages may be exaggerated or symptoms may be due to other sources such as medications taken concurrently. Some studies were done on children so the effects may have been increased.


EFFECTS OF KETOSIS
Ketosis creates a measurable amount of acetone in the mouth. (Remedial measure: brush teeth and mouth with baking soda, increase water intake, eat vegetables)

Ketosis decreases aspartate in the brain, but glutamate and glutamine remain unchanged with increase in glutamate conversion to GABA. (GABA controls nerve cells in brain from firing too fast. Same effect as when taking Valium). Utilization of neutral amino acids to increase glutamine.

3. 10% will have trouble reaching ketosis
4. 21% will have an intolerance of the rapid onset of ketosis
5. 41% will become constipated (Remedial measure: increase fiber intake)
6. 47% will experience hypoglycaemia (symptoms: fatigue, weakness, confusion, dizziness, irritability, a rapid heartbeat, anxiety, sweating, trembling, hunger, and headaches i.e. withdrawal symptoms from sugar addiction.)
7. 16% will refuse to drink fluids (which are critical to deter acid build-up during ketosis)
8. 16% will experience lack of appetite (this is good if you are on a weight loss diet)
9. 26% will have nausea and vomiting
10. 65% will have a rise in total serum cholesterol (although HDL will increase proportionally)
11. 32% will have periods of anorexia (aversion to food)
12. 9% will have symptomatic metabolic acidosis when associated with infection
13. 9% will have carnitine insufficiency during early part of ketogenic diet (supplement with L-Carnitine)
14. 8% will have high levels of uric acid in the urine (Drink water, eat vegetables, neutralize with bases)

Remember if these things above are the worse that can happen to you on a ketogenic diet that is tons better than heart disease, high LDL, diabetes, etc. SO DON'T FREAK OUT. Take supplements, drink plenty of water, and EAT YOUR VEGETABLES!

Some definitions are included at end of abstracts
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J Neurosci Res 2001 Dec 1;66(5):931-40

Ketogenic diet, amino acid metabolism, and seizure control.

Yudkoff M, Daikhin Y, Nissim I, Lazarow A, Nissim I.

Division of Child Development and Rehabilitation, Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104, USA. yudkoff~email.chop.edu

The ketogenic diet has been utilized for many years as an adjunctive therapy in the management of epilepsy, especially in those children for whom antiepileptic drugs have not permitted complete relief. The biochemical basis of the dietary effect is unclear. One possibility is that the diet leads to alterations in the metabolism of brain amino acids, most importantly glutamic acid, the major excitatory neurotransmitter. In this review, we explore the theme. We present evidence that ketosis can lead to the following: 1) a diminution in the rate of glutamate transamination to aspartate that occurs because of reduced availability of oxaloacetate, the ketoacid precursor to aspartate; 2) enhanced conversion of glutamate to GABA; and 3) increased uptake of neutral amino acids into the brain. Transport of these compounds involves an uptake system that exchanges the neutral amino acid for glutamine. The result is increased release from the brain of glutamate, particularly glutamate that had been resident in the synaptic space, in the form of glutamine. These putative adaptations of amino acid metabolism occur as the system evolves from a glucose-based fuel economy to one that utilizes ketone bodies as metabolic substrates. We consider mechanisms by which such changes might lead to the antiepileptic effect. Copyright 2001 Wiley-Liss, Inc.

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J Neurosci Res 2001 Oct 15;66(2):272-81
Brain amino acid metabolism and ketosis.

Yudkoff M, Daikhin Y, Nissim I, Lazarow A, Nissim I.

Division of Child Development and Rehabilitation, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. yudkoff~email.chop.edu

The relationship between ketosis and brain amino acid metabolism was studied in mice that consumed a ketogenic diet (>90% of calories as lipid). After 3 days on the diet the blood concentration of 3-OH-butyrate was approximately 5 mmol/l (control = 0.06-0.1 mmol/l). In forebrain and cerebellum the concentration of 3-OH-butyrate was approximately 10-fold higher than control. Brain [citrate] and [lactate] were greater in the ketotic animals. The concentration of whole brain free coenzyme A was lower in ketotic mice. Brain [aspartate] was reduced in forebrain and cerebellum, but [glutamate] and [glutamine] were unchanged. When [(15)N]leucine was administered to follow N metabolism, this labeled amino acid accumulated to a greater extent in the blood and brain of ketotic mice. Total brain aspartate ((14)N + (15)N) was reduced in the ketotic group. The [(15)N]aspartate/[(15)N]glutamate ratio was lower in ketotic animals, consistent with a shift in the equilibrium of the aspartate aminotransferase reaction away from aspartate. Label in [(15)N]GABA and total [(15)N]GABA was increased in ketotic animals. When the ketotic animals were injected with glucose, there was a partial blunting of ketoacidemia within 40 min as well as an increase of brain [aspartate], which was similar to control. When [U-(13)C(6)]glucose was injected, the (13)C label appeared rapidly in brain lactate and in amino acids. Label in brain [U-(13)C(3)]lactate was greater in the ketotic group. The ratio of brain (13)C-amino acid/(13)C-lactate, which reflects the fraction of amino acid carbon that is derived from glucose, was much lower in ketosis, indicating that another carbon source, i.e., ketone bodies, were precursor to aspartate, glutamate, glutamine and GABA. Copyright 2001 Wiley-Liss, Inc.
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Rev Neurol 2001 Nov 16-30;33(10):909-15
[Complications of treatment of epilepsy by a ketogenic diet]

[Article in Spanish]

Rios VG.

Saniago del Estero 2475, Santa Fe, 3000, Argentina.

INTRODUCTION: It was originally claimed that the ketogenic diet (KC) caused no major adverse effects. Few studies have been done to analyze the side effects and complications of the KC. OBJECTIVES: To analyze the side effects and complications seen in a group of patients on KC compared with those described in the international literature. PATIENTS AND METHODS: We made a prospective evaluation of 22 patients aged between one and nineteen years, over an average period of 25 months. All had some type of refractory epilepsy and had been included in a group treated following classical KC guidelines. RESULTS: The side effects and complications during admission were delay in onset of the ketotic state (10.5%), intolerance of the rapid onset of ketosis (21%), hypoglycaemia (47.37%), refusal to drink fluids (15.79%), lack of appetite (15.79%), and nausea and vomiting (26.31%). During treatment the serum cholesterol rose in 64.7% of the children, 40.91% were constipated, 31.82% had periods of anorexia, symptomatic metabolic acidosis occurred during intercurrent infections in 9.09%, renal calculi in 9.09%, carnitine insufficiency in 9.09% and severe complications which led to hospital admission in 21.05%. CONCLUSIONS: Our group of patients had no more side effects or complications than those described in the literature. KC may lead to complications, especially when strict guidelines for control and follow up are not used. However, they are usually easy to correct if detected early.------------------------------------------

Pediatr Neurol 2002 Apr;26(4):288-92

The ketogenic diet: a review of the experience at Connecticut Children's Medical Center.

DiMario FJ, Holland J.

Department of Pediatrics, University of Connecticut School of Medicine, Division of Pediatric Neurology at Connecticut Children's Medical Center, 06106, Hartford, CT, USA

We undertook a retrospective analysis of epilepsy patients referred and treated for more than 6 months with the ketogenic diet during 1994-1999 at Connecticut Children's Medical Center. Outcome measures included antiepileptic drug number, seizure frequency, electroencephalogram background/paroxysmal activity, and adverse effects at 6 months and 1 year on the ketogenic diet. The final cohort included 24 of 48 referred patients (mean age, 6.5 years; range = 1-15 years of age). The etiology of epilepsy was equally divided between idiopathic and cryptogenic epilepsy and symptomatic epilepsy. Intention to treat analysis revealed that 35% (17 of 48) achieved more than 50% reduction in seizure frequency, and 8.5% (four of 48) were seizure-free by 6 months. A sustained 50% or greater reduction at 1 year was observed in 23% (11 of 48), and the same 8.5% (four of 48) remained seizure-free. None of these improvements were statistically related to age (P = 0.97), sex (P = 0.78), or epilepsy etiology (P = 0.80). The number of antiepileptic drugs used per patient decreased. Electroencephalogram at 1 year demonstrated an improvement in background in 31% (five of 16 patients) and a reduction in paroxysmal features in 37.5% (6 of 16 patients). Most adverse effects were mild, self-limited, and occurred early. Hyperuricemia (more than 6 mg/dL) was more persistent in three patients.

PMID: 11992756 [PubMed - in process]

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Epilepsy Res 2002 Feb;48(3):221-7
The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience.

Coppola G, Veggiotti P, Cusmai R, Bertoli S, Cardinali S, Dionisi-Vici C, Elia M, Lispi ML, Sarnelli C, Tagliabue A, Toraldo C, Pascotto A.

Clinic of Child Neuropsychiatry, Second University of Naples, Via Pansini 5, 80131, Naples, Italy

Purpose: This collaborative study by three Italian groups of child neuropsychiatrists was carried on to evaluate the efficacy and safety of the classic 4:1 ketogenic diet as add-on treatment in refractory partial or generalized epilepsy in children, adolescents and young adults. Methods: We performed a prospective add-on study in 56 refractory epilepsy young patients (age 1-23 years, mean 10.4 years), all with both symptomatic and cryptogenic, generalized or partial epilepsies. Child neuropsychiatrists worked with nutritional team for sample selection and patients management. The ketogenic diet was added to the baseline antiepileptic drugs and the efficacy was rated according to seizure type and frequency. During treatment, seizure frequency, side effects, urine and blood ketone levels and other parameters were systematically evaluated. Results: Patients have been treated for 1-18 months (mean 5 months). A >50% reduction in seizure frequency was gained in 37.5 and 26.8% of patients after 3 and 6 months, respectively, at 12 months, this number fell by 8.9%. No significant relationship between diet efficacy and seizure or epilepsy type, age at diet onset, sex and etiology of epilepsy was noted. Nevertheless, it seems noteworthy that 64% of our patients with neuronal migration disorders improved on this diet. Adverse effects occurred, mainly in the first weeks of treatment, in 32 patients (57.1%), but were generally mild and transient. In seven patients (12.5%) it was possible to withdraw one to two AED after 3-4 months on ketogenic diet. Conclusion: This initial experience with the ketogenic diet was effective in difficult-to-treat patients with partial and generalized epilepsies, though its efficacy dropped significantly by 9-12 months.

PMID: 11904241 [PubMed - in process]

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Epilepsia
Volume 42 Issue 11 Page 1445 - November 2001

Carnitine Levels and the Ketogenic Diet
*Elizabeth Berry-Kravis, *Gayle Booth, *Ana Carolina Sanchez, and *Jean Woodbury-Kolb
Purpose: To determine the long-term effect of the ketogenic diet (KD) on carnitine levels and whether carnitine depletion is a significant cause of clinical complications during KD initiation or treatment.
Methods: Carnitine levels at 0, 1, 6, 12, and 24 months of diet treatment, carnitine antiepileptic drug (AED) history, lowest blood glucose and time to achieve ketosis during diet initiation, and diet complications were analyzed for 38 consecutive patients who initiated the KD from May 1997 to March 2000. Carnitine levels at follow-up were analyzed for eight patients started on the diet before to May 1997.
Results: Total carnitine (TC) at diet initiation correlated negatively with the number of AEDs at diet initiation but not with number of past AEDs, lowest blood glucose, or time to ketosis. TC decreased in the first months of diet treatment and then stabilized or increased slightly with long term treatment. Only 19 of patients were supplemented with carnitine for low TC. No patient showed clinical signs of carnitine deficiency.
Conclusions: Multiple AED exposure lowers TC, but actual TC deficiency in patients initiating the KD is not common, and TC levels do not appear to predict hypoglycemia or problems achieving ketosis. Mild carnitine depletion may occur early in KD treatment and occasionally TC decreases out of the normal range, without clinical symptoms. TC stabilizes or increases back toward baseline with long-term treatment, and most patients do not require carnitine supplementation.
aspartate
<amino acid> A nonessential amino acid that plays a critical part of the enzyme in the liver that transfers nitrogen-containing amino groups, either in building new proteins and amino acids or in breaking down proteins and amino acids for energy and detoxifying the nitrogen in the form of urea.
Depleted levels of aspartic acid may occur temporarily within certain tissues under stress, but, because the body is able to make its own aspartic acid to replace any depletion, deficiency states do not occur.
Aspartic acid is abundant in plants, especially in sprouting seeds. In protein, it exists mainly in the form of its amide, asparagine.
The popular sweetener Aspartame is a combination of aspartic acid and phenylalanine. Aspartic acid is considered nontoxic.
GABA
gamma aminobutyric acid
<biochemistry> An important amino acid which functions as the most prevalent inhibitory neurotransmitter in the central nervous system.
Gamma aminobutyric acid works in partnership with a derivative of Vitamin B-6, pyridoxine, to cross from the axons to the dendrites through the synaptic cleft, in response to an electrical signal in the neuron and inhibits message transmission. This helps control the nerve cells from firing too fast, which would overload the system.
The action of gamma aminobutyric acid decreases epileptic seizures and muscle spasms by inhibiting electrical signals in this manner. Studies have shown that the site of action in the brain of benzodiazepams, including Valium, is directly coupled to the brain receptor for gamma aminobutyric acid.

Acetone
(Ketone, Dimethyl)

Toxicity
Toxicity Data (Remember acetone levels never get this high during a ketogic diet)
· UNR-MAN LDLO: 1159 mg/kg
Target Organs:
· Brain and Coverings (Recordings from specific areas of cns)
· Sense Organs (Other olfaction effects)
· Sense Organs (Conjunctiva irritation)
· Behavioral (General anesthetic)
· Behavioral (Muscle weakness)
· Behavioral (Muscle contraction or spasticity)
· Lungs, Thorax or Respiration (Respiratory depression)
· Lungs, Thorax or Respiration (Other changes)
· Kidney, Ureter, or Bladder (Renal function tests depressed)
· Fertility (Post-implantation mortality)
Only selected entries shown here.
Effects:
· Inhalation: irritating to mucous membranes and upper respiratory tract.
Synonyms
Acetone (german, dutch, polish)
Chevron Acetone
Dimethylformaldehyde
Dimethylketal
Dimethyl Ketone
Ketone Propane
Beta-ketopropane
2-Propanone
Pyroacetic Acid
Pyroacetic Ether
CAS # 67-64-1
Incompatibles
Bases
Oxidizing Agents
Reducing Agents
Structure
Formula: C3H6O