The ketogenic or “keto” diet is a very low-carbohydrate, high-fat, moderate-protein regimen that results in the generation of ketones in the body. It was initially developed to treat epilepsy in the 1920s and was popular through the 1930s, when new anticonvulsant drugs started to fill most needs1. For the 25-50% of epileptics who cannot successfully control their seizures with medication – mostly children – the diet is still considered to be an important tool1,2. Because of its success, related research interest has expanded into other neurological disorders, MS included2.

   Ketones generated when following a keto diet include β-hydroxybutyrate (BHB), which has been found to activate receptors expressed by neuroinflammatory cells, reducing neuroinflammation and achieving a neuroprotective effect in MS3. No less importantly, a keto diet may restore myelination and reduce nerve cell degeneration, as was observed in an animal model of Pelizaeus-Merzbacher disease (a fatal and incurable leukodystrophy)4.

In an animal model of MS, a keto diet was shown to improve motor disability and brain “flexibility,” as well as spatial learning and memory. Moreover, disease-specific increases in inflammatory cytokines/chemokines and free radicals were suppressed, and brain atrophy and lesions were reversed5.

     In an open (uncontrolled) clinical study in RRMS patients, a modified Atkins keto diet (<20 g carbohydrate per day) followed for six months was associated with decreased fatigue, depression, and disability6.

In a randomized, controlled clinical study, RRMS patients and healthy controls implemented a keto diet (average daily intake of <50 g carbohydrates, >160 g fat, and <100 g protein) for six months. The diet was found to be associated with a more improved colonic microbiome in the MS group compared to controls. Colonic microbiome and neuropathology are closely interrelated, with concentrations of beneficial biofermentative bacteria being significantly reduced in MS patients7.

     In clinical studies of all MS patients using nearly the same keto intervention – with the exception of an omega-6 to omega-3 fatty acid ratio of 2:1 – vs. control diet, researchers found significant improvements in pro-inflammatory enzymes, related MS-specific quality of life8, and a biomarker of brain volume and neuronal damage from pre- to post-keto not observed in controls9.

     In a keto diet, the only foods considered “forbidden” are those very high in sugar/carbohydrates and low in fat. Beyond that, it is a matter of fitting foods and their respective portion sizes into the scheme of approximately 70-80% of calories from fat, 10-20% from protein, and 5-10% from “available” carbohydrates (not including insoluble/indigestible fiber). There may or may not be caloric restriction involved, but special attention should still be paid to the quality of foods included in order to meet nutritional needs and avoid chronic side effects.

Foods to Favor (high-fat and/or low-carbohydrate and -protein*)

Produce

• Avocado and its products (e.g., spreads and oil)

• Coconut and its products (e.g., butter, cream, milk, oil)

• Olives and their products (e.g., spreads and oil)

• Non-starchy vegetables (especially leafy and white ones)

• Low-sugar fruits (e.g., cantaloupe, casaba melon, raspberries, strawberries, watermelon)

Nuts and Seeds

• Nuts and their products (e.g., flours, butters with no sugar added) other than peanut

• Seeds and their products (e.g., flours, butters such as tahini)

Animal Foods

• Egg, whole and yolk (*fairly equally high in protein and fat)

• High-fat dairy and alternatives (no sugar added)

• Dairy butter (e.g., cow, goat)

Fats and Oils

• Margarine and shortening (for general health reasons, it is best to stick with “smart” trans-fat-free options based on healthful oils)

• Lard and tallow (for general health reasons, pastured/grass-fed is best)

• Oils (for general health reasons, it is best to avoid corn, soy, and regular sunflower/safflower)

Starch Alternatives

• “Skinny” noodles (e.g., from konjac)

• “Skinny” rice (e.g., from konjac)

• “Keto” rice (e.g., from cauliflower)

• “Keto” breads and bread products (e.g., from coconut and almond)

• “Keto” flours and flour products

Other

• Non-caloric sweeteners (recommended: natural options like Stevia and erythritol)

• Herbs and spices

• High-fat/low-carbohydrate toppings (e.g., aioli, au jus, gravy without regular flour, guacamole, lemon/lime juice, mustard, salad dressing with no sugar added, vinegar)

• Beverages not sweetened with sugar (e.g., homemade fruit waters, coffee, tea, tea-like infusions)

Foods for Moderation (moderate fat, moderate protein, moderate carbohydrate)

Produce

• Moderate starch vegetables (e.g., carrot, pumpkin, spaghetti squash, tomato)

• Moderate sugar fruits (e.g., apricot, blueberries, boysenberries, grapefruit, kiwi, lychee, orange, peach, persimmon, plum, pomegranate, tangerine)

Legumes

• Peanuts and their butter (no sugar added)

Animal Foods and Alternatives

• Fatty fish (e.g., herring, mackerel, salmon, sardines, swordfish, trout, tuna)

• Poultry (skin included)

• Red meat (though some keto plans recommend selecting higher-fat meats, this is only a healthful choice if using pastured/grass-fed – otherwise, it may be more advantageous to choose lean meats and make up the extra fat from plant sources)

• Egg whites and products (e.g., pourable “heart-healthy” eggs)

• Low-fat dairy and alternatives (no sugar added)

• Tofu (from soy or chickpeas)

• Tempeh

• Seitan (gluten)

Other

• Sugary sweeteners/toppings (honey, jams, jellies, maple syrup, molasses)

• Ketchup/catsup (no sugar added)

• Gravy (with regular flour)

• Alcohol, unsweetened, including light beer (metabolized like fat, but temporarily prevents the body from utilizing fat stores for energy)

Foods to Forgo (low-fat, low-protein, high-carbohydrate)

Produce

• Starchy vegetables (e.g., acorn squash, artichokes, cassava, corn, parsnips, potatoes, sunchokes, sweet potatoes, yams)

• High-sugar fruits (e.g., apples, bananas, grapes, pears, pineapple)

Legumes

• Legumes and their products (e.g., vegan egg substitutes, hummus, lentil noodles)

Animal Foods and Alternatives

• Fat-free dairy and alternatives

Starch

• Breads and bread products (non-keto, e.g. from potato, rice, wheat)

• Breakfast cereals, hot and cold (non-keto, e.g. from oats, rice, wheat)

• Flours and flour products (non-keto)

• Pasta (non-keto), including rice and white mung bean noodles

• Rice and rice-like grains (e.g., barley, bulgur, millet, quinoa)

Others

• Sugar and sugar-sweetened foods and beverages (especially fructose)

• Regular beer

Supplements

Because the keto diet tends to limit the amounts of certain food groups, nutrient deficiencies may develop. The following are the most common:

• Vitamin A

• Vitamin C

• Vitamin D

• Vitamin E

• Folate

• Calcium

• Chromium

• Iodine

• Iron

• Magnesium

• Molybdenum

• Potassium

• Biotin

• Fiber

     Therefore, it is recommended to consider calcium, multivitamin-mineral (“multiple”), and fiber (unsweetened) supplements. Because the mineral potassium is limited in over-the-counter amount, it may be advantageous to have your healthcare provider monitor your blood levels and to get a prescription potassium product as needed.

References

1. Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. Mar 2007;119(3):535-43. doi:10.1542/peds.2006-2447

2. Gough SM, Casella A, Ortega KJ, Hackam AS. Neuroprotection by the Ketogenic Diet: Evidence and Controversies. Front Nutr. 2021;8:782657. doi:10.3389/fnut.2021.782657

3. Jang J, Kim SR, Lee JE, et al. Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases. Int J Mol Sci. Dec 21 2023;25(1)doi:10.3390/ijms25010124

4. Stumpf SK, Berghoff SA, Trevisiol A, et al. Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease. Acta Neuropathol. Jul 2019;138(1):147-161. doi:10.1007/s00401-019-01985-2

5. Kim KY, Yang WJ, Shin TK, Jeong HJ, Kim HM. Impact of acupuncture by using life-energy (qi) oriental needle on the paralysis of rats with experimental autoimmune encephalomyelitis. Am J Chin Med. 2012;40(4):769-78. doi:10.1142/S0192415X12500577

6. Brenton JN, Banwell B, Bergqvist AGC, et al. Pilot study of a ketogenic diet in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm. Jul 2019;6(4):e565. doi:10.1212/NXI.0000000000000565

7. Swidsinski A, Dorffel Y, Loening-Baucke V, et al. Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple Sclerosis and Their Improvement with Ketogenic Diet. Front Microbiol. 2017;8:1141. doi:10.3389/fmicb.2017.01141

8. Bock M, Karber M, Kuhn H. Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis. EBioMedicine. Oct 2018;36:293-303. doi:10.1016/j.ebiom.2018.08.057

9. Bock M, Steffen F, Zipp F, Bittner S. Impact of Dietary Intervention on Serum Neurofilament Light Chain in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. Jan 2022;9(1)doi:10.1212/NXI.0000000000001102