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Multiple Sclerosis

Episodes

Posted on September 5th 2019 (almost 6 years)

Dr. Longo discusses his work that indicates that the fasting-mimicking diet holds promise for the treatment of autoimmune diseases, particularly multiple sclerosis.

Posted on September 5th 2019 (almost 6 years)

Dr. Valter Longo discusses how cellular repair mechanisms may have evolved during times of fasting, but are latent in times of food abundance.

Posted on July 15th 2019 (almost 6 years)

Dr. Valter Longo describes how the fasting-mimicking diet can be beneficial in the treatment of various diseases, including multiple sclerosis.

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News & Publications

  • Blocking a key regulator of autoimmunity reduces the inflammation associated with multiple sclerosis.

    A protein found on the surface of some immune cells regulates autoimmunity in multiple sclerosis, a new study has found. Blocking the protein’s activity reduced the inflammation associated with the disease.

    Researchers studied the role that the aryl hydrocarbon receptor – a protein found on specific immune cells called T cells – plays in autoimmunity in a mouse model of multiple sclerosis. They bred mice that lacked the aryl hydrocarbon receptor and examined the effects its absence had on T cell activity.

    They found that the absence of the aryl hydrocarbon receptor altered the types and numbers of microbial metabolites produced in the animals' guts. Specifically, the microbes produced more bile acids and short-chain fatty acids – both of which exhibit robust anti-inflammatory properties.

    Multiple sclerosis (MS) is a progressive autoimmune disorder that targets the central nervous system. A dominant feature of MS is inflammation of the nerves. T cells play an instrumental role in the inflammation and pathophysiology of MS.

    These findings suggest that blocking the key regulator of inflammation in MS prevents the inflammation associated with the disease. Some evidence suggests that the fasting-mimicking diet reduces the number of autoimmune cells in people with multiple sclerosis. Learn more in this episode featuring Dr. Valter Longo.

  • From the article:

    The third trimester of pregnancy has been previously shown to reduce relapse rates by approximately 70 percent as compared to before pregnancy, and other studies have shown benefit over the long term due to multiple pregnancies. An estrogen unique to pregnancy that is made by the fetus and placenta has been proposed by Dr. Rhonda Voskuhl and colleagues to mediate this pregnancy protection in both the MS mouse model as well as in two successfully completed clinical trials of estriol treatment in MS patients.

    How that happens has remained a critical question. Voskuhl, who led the latest study, reported mouse studies showing that estrogen protected the brain from damage by activating a protein called estrogen receptor beta (ERb). Her new research identifies which cells within the brain are mediating this protective effect.

    The researchers first genetically eliminated ERb in either immune cells of the brain or in oligodendrocytes, the cells that make the myelin sheath, as a way of making cells unresponsive to estrogen during the MS like disease in mice. They then treated mice without or with ERb in these cells to ask if disease protection was lost or not. Loss of protection during treatment meant that the treatment was acting on the cell that had the receptor removed. Results showed that the estrogen-like treatment was acting on both immune cells of the brain as well as on oligodendrocytes, together resulting in repair of myelin and less disability.

    View full publication

  • From the article:

    Nancy L. Sicotte, M.D., of the David Geffen School of Medicine at UCLA, Los Angeles, and colleagues conducted a study of testosterone treatment in 10 men with relapsing-remitting MS, characterized by periods of neurologic symptoms (such as numbness or difficulty walking) followed by periods of remission. The men, who had an average age of 46, were enrolled in the study and then entered a six-month pre-treatment phase, during which symptoms were monitored but no therapies were administered. Then, each man applied 10 grams of a gel containing 100 milligrams of testosterone to his upper arms once daily for 12 months.

    “One year of treatment with testosterone gel was associated with improvement in cognitive performance and a slowing of brain atrophy [deterioration],” the authors write. During the first nine months of the study – the period of time before the men began taking testosterone, plus the first three months of treatment, before it had time to take effect – brain volume decreased an average of -0.81 percent per year.

    In the second nine months, this decline slowed by 67 percent to an annual rate of -0.25 percent. “Because the protective effect of testosterone treatment on brain atrophy was observed in the absence of an appreciable anti-inflammatory effect, this protection may not be limited to MS, but may be applicable to those with non-inflammatory neurodegenerative diseases,” including amyotrophic lateral sclerosis or Lou Gehrig’s disease, the authors write.

    In addition, lean body mass (muscle mass) increased an average of 1.7 kilograms (about 3.74 pounds) during the treatment phase. Participants did not report any adverse effects, there were no abnormalities in blood tests taken during the trial and the men’s prostate examination results remained stable.

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  • From the article:

    The UNC scientists treated those mice and others whose genes were functional with a toxin called cuprizone that slowly stripped away the myelin coating on nerves in their brains and then observed myelin regeneration indicative of nerve repair. Normal mice recovered completely, but those lacking the functioning tumor necrosis factor-alpha gene did not, which indicated how critical the protein was to the repair process.

    “We’ve found that these tumor necrosis factor molecules are very important for the white matter in the brain to repair itself,” Ting said. “White matter is part of the brain that allows motor skills, and if you don’t have it, you can’t move.”

    “We further found that the repair process acts through a particular pathway that appears to induce the production of nerve precursor cells,” Arnett added. “Those cells will eventually differentiate into oligodendrocytes – cells that make myelin and surround nerve axons.”

    […]

    Recent clinical trials of several drugs designed to block the alpha form of TNF, which was considered to be a problem, actually made patients’ conditions worse, Arnett said. In part, the UNC experiments were designed to find out why.

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  • From the article:

    To create a stressful environment, researchers housed three young male mice together for several weeks. After the mice established a stable social hierarchy, researchers introduced an older aggressive male into the residence for a couple of hours. The intruder exhibits aggressive behavior – posturing, fighting, wounding, pursuit – that results in submissive behaviors and social defeat in the younger resident mice. This procedure was repeated for three consecutive nightly two-hour sessions with one night off, followed by an additional three nightly sessions. To keep the mice from getting used to the intruder, a new intruder was introduced for each session.

    What they found was this stress appears to elevate levels of IL-6, which subsequently increases the severity of the MS-like illness. Furthermore, using specific IL-6 neutralizing antibody treatments during the stress exposure can prevent the stress-related worsening of the disease, said the authors.

    […]

    Furthermore, interventions that prevented or reversed the stress-induced increases in IL-6 in the mouse model may have implications for humans, said Meagher. It is possible that the adverse effects of social conflict on people who are vulnerable to certain inflammatory diseases may be prevented or reversed by treatments aimed at blocking increases in this cytokine. Recent evidence suggests that some potential interventions include certain anti-inflammatory drugs, exercise, antidepressant medication, omega-3 fatty acids, and mindfulness relaxation training. However, human clinical trials are needed to fully evaluate this issue.

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  • Antibodies that destroy myelin in multiple sclerosis may cross-react with casein, a milk protein.

    Multiple sclerosis (MS) is a neurodegenerative and autoimmune disease caused when the immune system attacks myelin proteins on nerves, mistaking them for proteins produced by pathogens. The cause of this immune confusion is complex but may involve exposure to proteins found in cow’s milk, which anecdotally worsen MS symptoms for some patients. New research supports this anecdotal evidence, finding that MS autoantibodies cross-react with casein, the principal protein in cow’s milk.

    In order to create antibodies that react to new pathogens, B cells (a type of immune cells) use somatic hypermutation, a process during which they intentionally mutate regions of their DNA involved in antibody production. These rapid mutations are needed to increase antibody repertoire, the collection of an individual’s B cell receptor and antibody sequences; however, somatic hypermutation can result in the creation of autoantibodies, which bind to self-proteins produced by the body. While autoimmune B cells are usually destroyed shortly after creation, lingering autoimmune cells can proliferate and lead to diseases such as type 1 diabetes, rheumatoid arthritis, and MS. One reason autoantibodies persist is cross-reactivity with other proteins, such as those produced by pathogens or absorbed from the diet, especially in cases where gut leakiness increases the introduction of new proteins to the blood.

    The investigators gave one group of mice an injection of casein with adjuvants, which are compounds added to vaccines to increase the body’s antibody response. To compare casein to other milk proteins, they also immunized one group of mice with alpha-lactalbumin and another with beta-lactoglobulin, both whey proteins, for a total of three mouse groups. Changes in behavior and nerve degeneration were observed at 13, 20, or 40 days after immunization. The researchers also collected blood samples from 39 patients with MS and 23 patients with other neurological diseases in order to test for cross-reactivity of autoantibodies with casein.

    Mice immunized with casein exhibited a range of MS symptoms such as weakness and disorientation, while mice immunized with whey proteins did not. Immunization with casein led to a progressive increase in casein-reactive antibodies and deterioration of myelin in nerves of the lower spinal cord. The researchers found that casein-immunized mice produced autoantibodies that cross-react with myelin-associated glycoprotein (MAG), a protein produced by nerve cells called oligodendrocytes, which have a similar structure to casein. Finally, they found that 42 percent of participants with MS had casein-reactive antibodies compared to only 28 percent of participants with other neurological disorders.

    While it is not clear from these results what role dairy consumption plays in the development of MS, the authors suggest that some patients with MS may benefit from restricting dairy in their diet.

  • Epstein-Barr virus is one of the most common human viruses in the world. It is the primary cause of mononucleosis (often called “mono”) – a highly infectious disease that affects mostly teenagers and young adults. Findings from a recent study suggest that Epstein-Barr infection increases a person’s risk for developing multiple sclerosis.

    Multiple sclerosis is an autoimmune disorder characterized by the progressive destruction of myelin – the insulating sheath that surrounds nerves and facilitates neural transmission. The disease affects approximately 3 million people worldwide and is twice as likely to manifest in women than men. Symptoms of multiple sclerosis typically appear between the ages of 20 and 50 years.

    The study investigators analyzed blood samples from more than 10 million active duty military personnel, collected during routine health exams over a period of 20 years. From this group, they identified 801 personnel who had been tested for Epstein-Barr virus and later developed multiple sclerosis while on active duty. The investigators looked for the presence of antibodies in the blood samples that signaled past Epstein-Barr infection, as well as a protein called neurofilament light chain, a marker of myelin degeneration.

    They found that the average age at which personnel were diagnosed with Epstein-Barr infection was 20 years; multiple sclerosis onset typically occurred approximately ten years later. The risk of developing multiple sclerosis later in life was 32 times higher after having experienced Epstein-Barr infection during young adulthood. Levels of neurofilament light chain were higher among the military personnel who had experienced Epstein-Barr infection.

    These findings suggest that Epstein-Barr virus is the causal factor in the development of multiple sclerosis and underscore the need for developing vaccines against the virus. Although there is no cure for multiple sclerosis, evidence suggests that the fasting-mimicking diet may be beneficial in treating the condition. Learn about the fasting-mimicking diet in this episode featuring Dr. Valter Longo.

  • Exposure to ultraviolet (UV) light is critical for maintaining many aspects of human health. For example, compounds present in the skin react to UV light, initiating the production of vitamin D, a steroid hormone that participates in many physiological processes. Similarly, photoreceptors in the eyes respond to UV exposure, modulating the regulation of circadian rhythms. Findings from a new study suggest that early life exposure to ultraviolet light reduces the risk of developing early-onset multiple sclerosis (MS).

    Multiple sclerosis is an autoimmune disorder characterized by the progressive destruction of myelin – the insulating sheath that surrounds nerves and facilitates neural transmission. The disease affects approximately 3 million people worldwide and is twice as likely to manifest in women than men. Symptom onset typically occurs between the ages of 20 and 50 years, but as many as [5 percent of people with MS experience early onset](https://pubmed.ncbi.nlm.nih.gov/11205364/], with symptoms manifesting during childhood or young adulthood.

    The study involved 322 children and young adults with MS (ages 3 to 22 years) and 534 healthy participants of similar ages and sexes. All the participants (or their parents) provided information about their medical history, place of residence, and sun exposure.

    The authors found that among the participants who reported having spent fewer than 30 minutes outside per day during the previous summer, 19 percent had MS, while only 6 percent did not. When they accounted for other risks associated with MS, such as smoking or being female, they found that those who spent 30 to 60 minutes outside per day were 52 percent less likely to develop MS, compared to those who spent fewer than 30 minutes outside per day.

    These findings suggest that early life UV exposure reduces the risk of developing MS. Although these findings were based on observational data and do not assign causality, the authors of the study pointed out that they align with results of other studies suggesting that low UV exposure is associated with other neurological diseases, including Parkinson’s disease, Alzheimer’s disease, and other forms of dementia. Although there is no cure for Parkinson’s disease, evidence suggests that the fasting-mimicking diet may be beneficial in treating the condition. Learn more about the fasting-mimicking diet in this episode featuring Dr. Valter Longo.

  • Myelin, a fatty substance that insulates nerve axons and facilitates nerve signal conduction, is produced by the oligodendrocytes of the central nervous system. Myelination, the process of accruing myelin, begins early in life and plays a critical role in cognitive development and life-long neuronal function. Findings from a new study suggest that N-acetylglucosamine, a sugar present in breast milk and widely available as a dietary supplement, promotes remyelination in people who have multiple sclerosis.

    Multiple sclerosis is an immune-mediated disorder characterized by an inability to remyelinate nerve axons subsequent to inflammatory damage. Symptoms of the disease vary and can include numbness or tingling in the limbs, difficulty walking, fatigue, and problems with vision and speech, among others. The disease affects more than 2 million people worldwide.

    The rodent study investigated the role of N-acetylglucosamine in a mouse model of multiple sclerosis. The authors of the study gave mice either N-acetylglucosamine or a placebo in their drinking water for three days. They assessed the mice for nerve axon damage and impaired motor function (likelihood of falling) while the mice walked on a spinning rod.

    The authors found that administration of N-acetylglucosamine protected nerve axon damage and prevented motor function losses in the mice that received the N-acetylglucosamine. They also reported unpublished data indicating that people with multiple sclerosis who have low levels of serum N-acetylglucosamine typically experience a more progressive disease course and greater disability than those with higher levels of the compound.

    Taken together, these findings demonstrate that N-acetylglucosamine may be beneficial in treating people who have multiple sclerosis. More research is needed to confirm this possibility.

    Interestingly, some evidence suggests that people who have multiple sclerosis experience functional improvements with the fasting-mimicking diet, a dietary strategy that promotes immune cell turnover. Learn more about the fasting-mimicking diet and multiple sclerosis in this clip featuring Dr. Valter Longo.

  • Objective: We hypothesize that different sources of lung irritation may contribute to elicit an immune reaction in the lungs and subsequently lead to multiple sclerosis (MS) in people with a genetic susceptibility to the disease. We aimed to investigate the influence of exposure to organic solvents on MS risk, and a potential interaction between organic solvents and MS risk human leukocyte antigen (HLA) genes.

    Methods Using a Swedish population-based case-control study (2,042 incident cases of MS and 2,947 controls), participants with different genotypes, smoking habits, and exposures to organic solvents were compared regarding occurrence of MS, by calculating odds ratios with 95% confidence intervals using logistic regression. A potential interaction between exposure to organic solvents and MS risk HLA genes was evaluated by calculating the attributable proportion due to interaction.

    Results: Overall, exposure to organic solvents increased the risk of MS (odds ratio 1.5, 95% confidence interval 1.2–1.8, p = 0.0004). Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB115, and absence of HLA-A02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure.

    Conclusion The mechanism linking both smoking and exposure to organic solvents to MS risk may involve lung inflammation with a proinflammatory profile. Their interaction with MS risk HLA genes argues for an action of these environmental factors on adaptive immunity, perhaps through activation of autoaggressive cells resident in the lungs subsequently attacking the CNS.

    http://n.neurology.org/content/neurology/early/2018/07/03/WNL.0000000000005906.full.pdf

  • Intermittent fasting (every other day) increased gut bacteria diversity and reduced inflammation, demyelination, and axonal damage in multiple sclerosis (MS) animal model. A small pilot trial in humans with MS showed many similar changes to the gut microbiome and blood adipokines such as leptin. The effects of fasting on immune cells included a reduction of pro-inflammatory IL-17-producing T cells and increased numbers of T regulatory cells which prevent autoimmunity.

    The small pilot trial in humans showed increased bacteria richness in species that have previously been shown to promote T regulatory cell accumulation in the colon.

    Interestingly, this study did what is called a metagenomic analysis and found that the ketone pathway was enhanced in the gut microbiome by intermittent fasting. This is super interesting because bacteria in the gut normally produce short chain fatty acids and ketones from fermentable fiber but suggests that the gut microbiome regulates its own ketone body metabolism during fasting!

  • A pilot study finds people with multiple sclerosis (and healthy controls) increased several species of beneficial gut bacteria and induced an anti-inflammatory immune response after supplementation with a strong, high CFU probiotic for 3 months.

    Multiple sclerosis patients also displayed a decrease in a type of immune cell called myeloid-derived dendritic cells which play a role in suppressing immune cells that prevent autoimmunity (called T-regulatory cells). Larger studies are needed to replicate these findings as well as investigate whether the probiotic supplementation has any effect on clinical symptoms.

    To my knowledge, there are exactly three brands that have this type of formulation of high CFU probiotic that seems to have a strong and growing body of clinical, published evidence: • VSL#3 (the original formulation) • Visbiome (a newer brand used in this study that is supposed to be substantially similar) • Vivomixx (European branded Visbiome)

  • This fasting-like diet also promotes regeneration of the myelin in mice with multiple sclerosis. In human patients with multiple sclerosis, the fasting-like diet led to improvements in symptoms if followed by a Mediterranean diet or a ketogenic diet.

    Here is the fasting-like diet that humans were given: Day 1 – pre-fasting followed by Day 2-8 – very low calorie diet. Day 1-prefasting consists of an 800 kcal (about 40% of normal caloric intake similar to mouse Day1 FMD) monodiet (fruit, rice, or potatoes) by preference of individuals. On the following day patients were recommended to use an oral laxative, Natrium Sulfuricum (20-40 g). FMD consisted of 100 ml vegetable broth or vegetable juice with 1tablespoon of linseed oil 3 times daily, plus additional calorie-free liquids. The daily calorie intake was predefined with 200 – 350 kcal (10-18% of normal caloric intake similar to mouse Day 2-3 FMD). Patients were advised to drink 2-3 L of unsweetened fluids each day (water, and herbal teas) and to use an enema if tolerated. After the 7-day fasting period solid foods were stepwise reintroduced for three days, starting with a steamed apple at day 8. After the fasting and refeeding period a normocaloric, plant-based Mediterranean diet was maintained until study end.