Melatonin and multiple sclerosis: Why MS symptoms may improve as the days get shorter

Exercising in winter


For patients and clinicians alike, it’s long been a mystery: why do symptoms of multiple sclerosis (MS) seem to get better in the winter and worse in the summer? A group led by Francisco Quintana, PhD, at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH) and collaborators have found an explanation that could lead to a deeper understanding of the disease and more targeted treatment options for patients. By first looking broadly at possible environmental factors and then deeply at preclinical models of MS, the research team found that melatonin – a hormone involved in regulating a person’s sleep-wake cycle – may influence MS disease activity. The team reports its findings this week in Cell.

The researchers caution that this work does not mean MS patients should start taking supplements of melatonin – an imperfect drug. Instead, this new approach – which takes its lead from environmental observations – can be seen as a first step toward better and more targeted therapies.

“We know that for multiple sclerosis and most autoimmune diseases, both genetic and environmental factors play an important role, but in the last decade or so, most research has focused only on the genetic side of the equation,” said co-corresponding author Quintana, associate professor in the Ann Romney Center for Neurologic Diseases at BWH. “But we wanted to see what environmental factors would reveal to us about this disease. We knew that MS disease activity changed with the seasons. What we’ve uncovered offers an explanation for why that is the case.”

Working closely with colleagues at the Center for Research on Neuroimmunological Diseases (CIEN) at the Raul Carrea Institute for Neurological Research (FLENI) in Argentina, Quintana and his colleagues began by studying patients. The team found that during the fall and winter, the group of 139 relapsing remitting MS patients they studied experienced a significant improvement in symptoms (a phenomenon that’s been observed in previous studies). The team then explored a variety of environmental factors that have been proposed as possibly linked to MS symptoms, including vitamin D levels, UV incidence and upper respiratory tract infections. But the factor that was consistently associated with severity of MS symptoms was melatonin. Melatonin levels are known to correlate with day length – during the longer days of the spring and summer, levels are lower and during the shorter days of the fall and winter, levels are higher.

Based on this observation, the team tested this lead in the lab, studying the role that melatonin may play on a cellular level. Using both a mouse model and human cells, they investigated the effects of melatonin on certain types of cells, known to play a role in the immune response that leads to MS symptoms. The team found that melatonin affected the roles of two kinds of cells that are important in MS disease progression: pathogenic T cells that directly attack and destroy tissue and regulatory T cells, which are supposed to keep pathogenic T cells in check.

“We found that melatonin has a protective effect,” said Quintana. “It dampens the immune response and helps keep the bad guys – or pathogenic T cells – at bay.”

Although melatonin is available over the counter, it has significant drawbacks, including causing unwanted drowsiness. The team’s goal is to tease apart the molecular mechanisms that underlie melatonin’s role in order to develop targeted, non-toxic drugs that are safe and effective with minimal side effects.

“In the future, melatonin or its derivatives may be used in MS patients after appropriate clinical trials are conducted and dosage is established,” said Quintana. “However, extreme caution should be exercised: our data do not show that melatonin or its analogs are effective in treating MS.”

The team is currently working to establish a pilot clinical trial to study the effects of targeting melatonin signaling in MS patients and identify additional mechanisms of action.

Autism – Tips for Parents and Caregivers – A Cross Post from Dr. Sonya Doherty




Getting a good night's sleep - some tips

Getting a good night’s sleep – some tips

Dr. Sonya Doherty has very kindly allowed us to republish this wonderful tips! for parents and caregivers of children on the autism spectrum.   Doherty is a licensed and board certified Naturopathic Doctor who is an active member of the CAND. Sonya Doherty completed her undergraduate training at the University of Western Ontario in a Bachelor of Science Honors Kinesiology program.  Very experienced in the field of autism you can access her website here.Sonya writes “I feel very lucky to work with so many wonderful families to help children reach their developmental potential. I wanted to write a special note to parents and caregivers about taking care of yourselves! It is my hope that you will all include in your 2011 resolutions to ensure that you are putting some time and effort into your own diet, health and relationships. The healthier parents are feeling, the more energy they have to support their children in all different avenues.




Here are some great tips for parents to consider:

Sleep

Sleep is often highly dependent on children’s routines. Ensure that your child has enough physiological support to maintain healthy sleep patterns. Melatonin, safe sleep supportive botanicals and homeopathics can help children have a deeper, longer, more restful sleep. Many parents have sleep issues of their own. Consider going to bed earlier to take the pressure off of your stress system. Research shows that healthy sleep patterns enhance immunity, energy levels and help individuals cope with stress more effectively.

Dr. Jill James, a PhD biochemist and principal investigator at the Arkansas Children’s Research Institute has identified a number of metabolic and biochemical abnormalities in children with autism. She has also found that parents of children on the autism spectrum often have “methylation defects” which increases their requirement for methyl-B12. Many of you have seen the incredible benefit of MB12 on children with developmental disorders. Parents who do not have a strong enough methylation cycle will have trouble making enough serotonin, putting their mood and sleep at risk for developing issues. Melatonin is the hormone that helps us naturally fall asleep. Melatonin is made from serotonin and vitamin D. A methylation issue could present in a parent with chronic sleep issues and supporting methylation can dramatically improve sleep quality and length (as long as kids cooperate!) as well as having a number of other positive health benefits including prevention of chronic disease.

Digestion

The digestive tract plays a number of essential roles. Energy, mood, regulation of inflammation and immune support are all mediated by a healthy digestive tract. Adults should be having (you know I love to talk about digestion!) 2-3 bowel movements daily that are easy to pass and shaped like an “S” or have a curve. If your digestion is not optimal, it is more difficult to produce energy and regulate inflammation which plays a role in weight regulation and disease prevention. Remember that 90% of serotonin is produced in the digestive tract




Essentials for the digestive tract:

Fiber

Water

Essential Fatty Acids

Probiotics

Consider the foods that disrupt your child’s digestive tract, behaviour, sleep and/or development. Part of our reactions to foods is genetically predetermined and many parents benefit from removing dairy and/or gluten from their diet. Other people have noticed significant health benefits from removing allergens identified through food allergy testing.

Energy and Mood

Who couldn’t use more energy? Most parents and caregivers are focusing so much on their children and day to day tasks, it is difficult to create opportunities to improve energy and/or mood. I believe that every parent should be on a stress system support protocol. Our adrenal glands process all of the stress in our body. Some signs your stress system is under pressure are fatigue, feeling overwhelmed and/or irritable, difficulty with mood regulation, afternoon drop in energy and/or sleep issues. Other people experience difficulty with focus and memory.

For more information, visit www.adrenalfatigue.org

  • B complex
  • Protein with every meal
  • Minimizing processed foods and sugar
  • B12 therapy

Sleep disorders and children diagnosed with autism. Read some amazing information in our guest post from Dr. Sonya Doherty




Dr. Sonya Doherty

Dr. Sonya Doherty




Welcome to our latest guest post from Dr. Sonya Doherty. You can read the original post on her blog here. Dr. Sonya Doherty is a licensed and board certified Naturopathic Doctor who is an active member of the CAND. Sonya Doherty completed her undergraduate training at the University of Western Ontario in a Bachelor of Science Honors Kinesiology program.

You may be also interested in a recent discussion blog we ran which looked at this very subject!

If you have a child diagnosed with autism, or who you suspect is on the spectrum, chances are your child is having trouble getting to sleep or staying asleep.  Sleep is essential to support optimal development.  Research at the Arkansas Children’s Research Institute has identified that 90% of children diagnosed with autism havemethylation impairments . Methylation impairment can change the way children produce brain chemicals like serotonin, dopamine, GABA, glutamate and norepinephrine.  With respect to sleep, serotonin is a much need neurotransmitter.  90% of serotonin comes from the gastrointestinal tract.  Up to 85% of children with ASD have digestive problems including constipation, diarrhea, pain and gut flora imbalance.  Serotonin is converted to melatonin with the help of vitamin D.  Vitamin D deficiency is well documented in the autism focused medical research. 




Adequate magnesium levels are required for healthy sleep onset and maintenance.  Many children with autism and ADHD have magnesium levels that are lower than normal.  Magnesium deficiency is the 4th most common nutrient deficiency in North America.  Nutrient deficiencies, digestive problems and methylation impairment combine to negatively impact healthy sleep patterns in ASD.  Children who are experiencing developmental concerns are at a substantially higher risk of experiencing sleep disorders.  The children who need sleep the most are having trouble getting to sleep, staying asleep,  having restful sleep are early waking.

Addressing sleep issues in children with autism is multi-faceted.  Many parents have altered routines to accommodate their child’s imbalanced circadian rhythm.  Putting children to sleep much later than same age peers, results in an exhaustion cycle that exacerbates behaviours and sensory overload.  Your child’s body has two ways to get to sleep. One is at their age appropriate bed time which is supported by appropriate melatonin levels.  The melatonin signal is initiated by darkness and regulates the sleep-wake cycle by causing drowsiness.  Limiting TV, iPads and other screens in the evening is important for children with sleep onset insomnia.  Blackout blinds are also crucial to help support the repair of your child’s sleep cycle.  Melatonin production must be stimulated to increase documented low levels experienced by children with an autism diagnosis.  Use of melatonin is an important “band aid” treatment during this time as children’s methylation cycle is supported and repaired.  Other helpful sleep supports include magnesium glycinate, GABA, L-theanine and botanical medicines like valerian, skullcap, lemonbalm, zizyphus and passionflower.

The importance of melatonin in the management of sleep disorders and gastrointestinal problems in children diagnosed with autism spectrum disorder:

One of the most common questions that I am asked by parents is about melatonin safety.  “Is it safe to give my child melatonin?”

I think the below information will make it clear that it may be unsafe not to give your child with autism melatonin.

The International Child Development Resource Center performed a systematic review and meta-analysis on melatonin and autism.  Their findings show that most children diagnosed with autism have:

  • Abnormalities in their melatonin levels
  • Gene abnormalities that contribute to lower melatonin levels
  • Show positive changes with respect to sleep duration, onset and night time waking
  • Show improvement in autistic behaviours

Sleep problems in autism usually start at the same age as developmental regression, suggesting a higher vulnerability at this period of life. Healthy sleep patterns are essential to support neuroplasticity and development so it is important to address sleep disorders as soon as possible.  According to the Center of Pediatric Sleep Disorders, studies of melatonin use in children with ASD provide evidence for its effectiveness and safety in the long run.

Melatonin, however, has a larger role to play in development beyond its function as a synchronizer of the biological clock. Melatonin is a hormone that helps in the regulation of the gastrointestinal system.  The gut is 100% responsible for post-natal development.  In the gut, melatonin, governs intestinal reflexes, motility, the immune function, gut secretions, energy balance, pain regulation and protects against inflammation.  The gut contains at least 400 times more melatonin than the pineal gland  The GI tract produces its own melatonin which suggests it plays a large role in maintaining gut health; both in a healthy digestive tract and in gut disorders.  Children diagnosed with ASD have alterations in their gut flora in addition to higher prevalence of constipation, diarrhea, reflux and pain.  The balance of good bacteria is not the same as typically developing children.  Melatonin levels change gut flora and improve anti-microbial actions.  With the startling numbers of children experiencing both gut issues and sleep issues, this new research about melatonin’s role in gastrointestinal health could provide clues about treatment and repair of these biological systems.

Other interesting information about melatonin:

  • Melatonin is also synthesized by the bone marrow cells, white blood cells, mast cells and skin cells
  • It is a powerful antioxidant
  • Melatonin helps to protect mitochondria from oxidative stress which damages cells
  • Melatonin also helps to support glutathione production.  Glutathione is widely considered the most important antioxidant in the body.  In another study, The Arkansas Children’s Research Institute found that children diagnosed with autism have up to 80% of their glutathione depleted.  Glutathione depletion may be part of the central mechanism for developmental delay because the role it plays in protecting the brain from toxicity
  • There is research to support that melatonin helps to support healthy immune function by fighting infectious disease including viral and bacterial infections
  • Melatonin has shown some promise in modulating the immune function in autoimmune disease