How Not to Treat Brain Fog

Q: Does Resveratrol Help Cognition? A: It Might Actually Do Harm.

Key Points:

  1. Resveratrol, a nutritional supplement, extends life span in animals; but, no studies clearly prove benefit for humans.
  2. A placebo controlled study using Resveratrol to treat Alzheimer’s found possible benefit, but not certain benefit for cognition. But, the Resveratrol group had more atrophy of the brain than those taking the placebo.
  3. My advice: Until we know more, remove Resveratrol from your wish-list of nutrients.

Resveratrol is a natural product found at low doses in grape skin and wine–especially red wine. Animals treated with Resveratrol might live longer and be less prone to cancer. But, we have no controlled studies in humans that show clear benefit for any health problems. Many people take Resveratrol hoping for health benefits. Several of my chronic fatigue and fibromyalgia patients take Resveratrol hoping it will reduce their “brain fog”.

Resveratrol molecule

New Published Research: Clinical scientists from Georgetown and other prestigious medical schools reported the first placebo controlled study using Resveratrol to treat people with mild to moderate Alzheimer’s disease. After one year on Resveratrol, cognitive decline was modestly less than among subjects who were taking placebo. But, the difference was not statistically significant.
And now the bad news, those taking Resveratrol had MORE atrophy (shrinkage) of their brains compared to those on placebo. This difference was statistically significant. Some atrophy of the brain “normally” occurs as we age. Atrophy gets worse among persons with Alzheimer’s.

I was alarmed that Resveratrol might shrink the brain. But to my surprise, the Georgetown researchers were not too concerned. They wrote, The etiology and interpretation of brain volume loss observed here and in other studies are unclear, but they are not associated with cognitive or functional decline.” (I think this means that the degree of brain atrophy did not track closely with the amount of cognitive decline.)

Still it’s very hard to see brain shrinkage as a virtue. Add in the fact that no human studies have yet shown clear benefit from taking Resveratrol, my advice for now is– Don’t Take Resveratrol.

Strengths of the Study: This was a well designed study done by reputable scientists.
Weaknesses: The number of subjects was fairly small—just 119 persons split between Resveratrol and placebo. The study ‘s one year duration is reasonably long, but might not be long enough to judge the long term benefits (or harms) caused by the treatment.
A counter argument: People who regularly drink modest amounts of wine are less likely to have heart attacks compared to those who never drink alcohol and also to people who drink to excess. Might the Resveratrol in wine contribute to this benefit? Possibly, though wine also contains many kinds of polyphenols and other components.

More important, the dose of Resveratrol available from wine, grapes and other foods is very much less than the dose sold in health food stores. Five ounces of red wine has just one or two milligrams (mgs) of Resveratrol. The Georgetown study treated with 500 to 2000 mgs per day. These extremely different dose levels should not be expected to create the same biological effects.

Can the Mediterranean Diet Help Clear “Brain Fog”?

Key Points:

  1. We have good evidence from a very large Spanish study that a “Mediterranean” Style Diet lowers heart attack rates compared to the low-fat American Heart Association Style Diet
  2. A recent study suggests that the Mediterranean Diet also helps prevent the cognitive decline that often occurs as we age.
  3. Would a Mediterranean style diet also help the “brain fog” that occurs with ME/CFS and Fibromyalgia? There’s been no formal research. Reports from patients who adopt this diet for several months would help us all learn more.

Patients often ask me, “Doctor, what should I eat to help me feel better?” Usually they have a specific diet in mind, for example, organic, gluten free, allergy elimination, anti-Candida yeast, and most often of late a Paleo(lithic)/cave man type diet. Patients with ME/CFS and Fibromyalgia (FM) are especially likely to say what can I do to help my “foggy” brain?

Now to the above list I’d like to add one more diet choice, a “Mediterranean” style diet. It almost certainly reduces the risk of heart attacks and stroke. It might also help prevent failing cognition as we age. Will it also help the “brain fog” of ME/CFS and FM? We can’t say yes or no. But, the evidence for it is at least as strong as or better than the diets listed above.

What is the Mediterranean Diet?

Mediterranean Diet

The Mediterranean Diet emphasizes eating “good fats”—mainly from olive oil and/or nuts.  It encourages fruits, vegetables, whole grain cereals and moderate portions of wine. Red meat (high in saturated fat) and high sugar junk foods are kept to a minimum. (See specific recommendations below.) There are two studies of note that focus on cognitive improvement and the Mediterranean diet: PREDIMED and MIND studies.

The PREDIMED Study
In 2013, Spanish researchers recruited 7,000 middle aged and older men and women for a long-term diet study called the PREDIMED study. Each volunteer agreed to be randomly assigned to either a high fat Mediterranean style diet with the main fat source being from either olive oil or nuts or to a diet modeled after the American Heart Association’s low fat recommendations. After 5 years, the rate of heart attacks was about 25% lower among those on the Mediterranean diet compared to those eating the American Heart Association style relatively low fat diet.

Among the several PREDIMED study centers, the research group in Barcelona selected 447 participants who were given a battery of cognitive skill tests at the start of the study. Most, but not all of these volunteers returned for repeat cognitive testing after about four years on their assigned diets. The initial scores on nine detailed cognitive tests were about the same for both groups. But at follow-up, the Mediterranean Diet group scored significantly higher than the low-fat-diet group for four of the nine cognitive tests—including two that were the most challenging and complex. The Mediterranean Diet group also outperformed the low-fat-diet group on the other five test scores, though these differences were not statistically significant. This suggests that the Mediterranean Diet might also prevent mild cognitive impairment (MC1).

Strengths of the recent study: The cognitive arm of the PREDIMED study was well designed. Its 4 year long follow up is also a plus.

Weaknesses: 447 patients are “small potatoes” compared to the 7,000 followed by all the PREDIMED study sites. Also about 100 of the original 447 subjects were not willing to come back for repeat cognitive testing after 4 years. So, the best we can say for now is that these results are encouraging and it seems fairly likely but not certain, that the high fat olive oil/nut Mediterranean style diet improves cognition among people as they age.

Caution: The Barcelona PREDIMED report is the only well designed long term controlled study where formal cognitive testing was done both before and after adopting the Mediterranean Diet. So, clearly, we need additional controlled trials before firmly accepting any conclusions.
Continue reading Can the Mediterranean Diet Help Clear “Brain Fog”?

Natural Treatments For Mild Cognitive Impairment– Might these also help the “fog” of FM and CFS?

brain fog and vitamin B

People who have chronic fatigue syndrome (CFS) and Fibromyalgia (FM) often struggle with a kind of mental “fog”. We don’t understand why and there’s been little research on how to think more clearly. Mild Cognitive Impairment or MCI presents with a different kind of cognitive “fog” but it’s form might feel familiar. MCI affects some 15-20% of Americans, aged 65 and older. While anyone can develop MCI, the risk is higher among people who have a high blood level of the amino acid homocysteine. High homocysteine also predicts a higher risk for developing full-fledged Alzheimer’s Disease.

Continue reading Natural Treatments For Mild Cognitive Impairment– Might these also help the “fog” of FM and CFS?

Powerful Proof that Symptoms of Chronic Fatigue Syndrome and Fibromyalgia are REAL and MAINLY PHYSICAL

I interviewed Dr. ALan Light, Ph. D by Skype in a three part video series. His research is among the very most innovative and important in the fields of chronic fatigue syndrome and Fibromyalgia. He, along with Lucinda Bateman, M.D. and colleagues from the University of Utah School of Medicine, has successfully conducted one study out of a very few that identify an objective laboratory marker which closely correlates with the patients’ “subjective” complaint of prolonged fatigue after modest exertion. This proves that the patients’ subjective reports of post-exertional malaise (PEM) are honest, real and based on physical events. More details on this study and its significance can be found on the following three 10-minute videos and text below.

Segment 1: Provides background on why and how this research was developed

Segment 2: Provides details about this critical study

Segment 3: Reactions from the scientific study and next steps

Details of Study

Dr. Light, Lucinda Bateman, M.D. and colleagues from the University of Utah School of Medicine measured output of messenger RNA output from 13 selected genes. They did this just before, shortly after, and for 48 hours following very modest exercise on a stationary bicycle. The subjects included 48 patients with CFS with or without co-occurring FM, 18 patients who had FM but not CFS, and 49 healthy controls. The 13 genes monitored related to sensory nerve signaling, cytokine and immune function and the sympathetic nervous system.

Results

All CFS and FM patients reported increased symptoms of pain or fatigue for a full 48 hours following the exercise. In controls, there was no reported fatigue and no significant change in gene expression. All subjects showed objective changes in the RNA output from key genes which also lasted a full 48 hours.

There were two distinct patterns of response: In 71% of patients with CFS moderate exercise increased messenger RNA output from 12 of the 13 genes. This was true whether or not they also had FM. Most of these genes related to inflammation or nerve signaling. In the other 29% of CFS patients, exercise caused a decrease in output of messenger RNA from an adrenalin related gene. Many of these patients also had a clinical history of orthostatic intolerance (low blood pressure with prolonged standing). In contrast, the FM-only patients showed no post exercise changes in gene expression.  Text on the full study and results can be found at http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02405.x/full
Significance

By showing changes in gene output this objectively proves that the fatigue and pain are real and are mainly physical., Dr. Light’s work appears to identify two different subgroups of CFS patients—one where pro-inflammatory genes turn on, and a second type where blood pressure tends to fall and an adrenalin related gene turns down its activity.  Dr. Light’s work also suggests that Fibromyalgia can occur in two different forms—one that is closely associated with CFS and one which is not.

Encouraging News on Namenda (memantine) for Pain

namenda for fibromyalgia pain
Pain in a woman’s body

I previously posted an analysis of a double blind study where Namenda, a medicine for Alzheimer’s, showed benefit for fibromyalgia pain.   In the previous study from Spain, Namenda was significantly better than a placebo for treating Fibromyalgia. But only a minority of patients improved. As importantly, it took a six-month’s long trial of treatment before the benefit from Namenda compared to placebo was statistically significant.

After reviewing that data, I had mixed feelings about recommending memantine for my patients. (I will now call Namenda “memantine,” the generic version which is much less expensive.)   Since then I’ve recommended memantine to five FMS patients. In a bow to reality, I suggested they try memantine for a two-month trial period, instead of the six months used in the double-blind study. The results; two patients improved meaningfully. One could not tolerate raising the dose. Two followed through but memantine did not help.

Now I’m writing to alert you to an encouraging study where memantine helped a very different kind of pain, the chronic pain that can occur from a mastectomy among women treated for breast cancer. (There have been no further studies on memantine and fibro.)    After mastectomy, 30% or more of women develop a burning or shooting pain in the chest, arm and armpit that lasts for three months or more. In a single blind study, 20 women received memantine for two weeks before and two weeks after their mastectomy. Twenty other women who had a mastectomy took a placebo.

After three months, the women rated the intensity of their pain on a scale of zero to ten. The results: Women who had taken memantine experienced substantially less pain than did the women who took placebo. The p value was 0.017. (Less than .05 is “significant”.) Memantine also reduced the need for prescription pain medicines. Only one of 20 women who had taken memantine needed a prescription compared to six of 20 women who had taken placebo. (Six months post operation memantine patients still had less pain, but the difference was no longer statistically significant.)

Take-Home Thoughts
Memantine is probably useful for some forms of pain. But we should keep in mind it might react differently for different forms of pain. Post-mastectomy pain results from obvious trauma to peripheral nerves. FM reflects abnormalities in the brain and the spine that are not classically “traumatic.”   Since we have only one controlled study for memantine and fibromyalgia, anecdotal experience might be our next most useful resource.

Some scientists doubt that anecdotes are useful. As a practicing physician, I strongly disagree. Anecdotal experiences can and should influence our judgments—especially if we can create a mechanism through which many, many individuals can share their experience.    The Internet has become such a mechanism. Our challenge: how to adapt this mechanism to the practical needs of clinicians, researchers and patients who care about Fibromyalgia, Chronic Fatigue Syndrome and related health problems.

memantine-graph
memantine results for pain

 

Two key questions: Who has the skill and the interest to create a practically useful forum on line? Who has the interest and ability to organize and/or provide the necessary funding?

Please feel free to comment especially if you have taken memantine for any type of pain.

Flexeril for Fibromyalgia Pain, Sleep Problems and Daytime Fatigue

Background
Flexeril (cyclobenzaprine) is FDA approved for the short term relief of “muscle spasm associated with acute, painful muscoskeletal conditions.” It’s not approved for long term usage or to treat Fibromyalgia (FM).

flexeril for fibromyalgia pain
fibromyalgia and fatigue

Still, Fibromyalgia specialists sometimes prescribe Flexeril for use as a sleeping aid and to reduce Fibromyalgia pain. But at standard doses, Flexeril’s sedating effect often carries over to the next day, worsening fatigue. There may be a better way of prescribing Flexeril; not only a way that improves sleep and pain, but to actually lessen feelings of daytime fatigue also.

Continue reading Flexeril for Fibromyalgia Pain, Sleep Problems and Daytime Fatigue

A NEW Form of MAGNESIUM: Can it help Brain Fog and FM Pain?

Background

Cognitive function tends to declines as we age. For most people the decline is modest. This “semi-normal” decline is thought to be due to a decrease in the ability of cells to communicate with each other through connections called synapses. A similar defect is seen with Alzheimer’s disease.

Magnesium for fibromyalgia
Magnesium for fibromyalgia

Animal studies show that one way to increase the number and function of synapses is to raise the brain’s level of the mineral magnesium. When scientists increase brain magnesium in lab rats, the rats become smarter. They can think more rapidly and accurately than they did before.

But, most forms of oral magnesium don’t pass easily from the blood into the brain. An exception is a new form of magnesium developed by a research team from MIT specifically for the purpose of passing from the blood into the brain. This form is magnesium threonate,.  It is being developed by Neurocentria, Inc., a pharmaceutical company, under the brand name of MMFS-01.

The Study

Neurocentria’s team recently published a very important study. Their results strongly suggest that MMFS-01 can substantially improve mild cognitive function in aging humans.  MMFS-01 is not yet commercially available.  However, a “generic” magnesium threonate is available from the Life Extension Foundation under the brand name of Neuro-mag. Likely other “generics” are or will soon be available.

What is truly remarkable about the MMFS-01 study is that improvement in over-all cognitive function was seen within just six weeks. Improvement continued through 12 weeks, the full length of the study.  Subjects treated with placebo did not improve overall.

Volunteers for the Neurocentria study were age 50 to 70. All had test score evidence of mild cognitive impairment. Twenty five subjects took MMFS-01 and 26 took placebo. The treatment dose was between 1.5 and 2.0 grams per day in divided doses.  Four different cognitive tests were taken before treatment and again at six and twelve weeks. These tests measured executive function, working memory, attention and a concept called episodic memory.

Findings: With magnesium threonate executive function significantly improved compared to placebo at 6 and 12 weeks.  Working memory improved significantly at six weeks but at 12 weeks the placebo group had improved also. So, the difference for working memory was no longer statistically significant.  Attention improved in the MMFS-01 group compared to baseline, but this improvement was not statistically better than for those taking placebo.  Episodic memory improved with MMFS-01 by week 12, but was not significantly better than that seen with placebo.

However, when overall cognitive ability was calculated by combining results from the four tests, subjects taking MMFS-01 scored significantly better than subjects taking placebo. This was true at week 6 (P=.017) and at week 12 (p=.003).  As important, subjects taking MMFS-01 who had the greatest increase in red blood cell magnesium levels were alsomost likely to show major cognitive improvement. There were no major side effects.

Separate research suggests that magnesium might also help for fibromyalgia pain. This benefit might be because magnesium tends to inhibit the activity of NMDA receptors. Activation of NMDA receptors is believed to be one mechanism that creates fibromyalgia pain.  A recent open label study from Mayo Clinic found that transdermal magnesium chloride spray taken twice daily for 3 weeks was followed by a reduction in fibromyalgia pain.

Take Home Thoughts

Should physicians treating FM or ME-CFS “brain fog” by offer magnesium threonate as a potential treatment?  The arguments against: 1) We don’t know whether brain fog in fibromyalgia or ME-CFS has any relationship to the cognitive decline that is common with aging. 2)  We have only one clinical study to support the beneficial effects of magnesium threonate.

The argument for: 1) Brain fog is a major problem for our patients 2) We have no proven treatments 3)  For most (but not all patients), side effects from magnesium are minimal—mainly diarrhea if we get the dose up too high.

Should patients with FM or ME-CFS try magnesium threonate on their own?  I strongly recommend that all patients work with their doctor.  Certain patients should not take extra magnesium, especially those with any degree of kidney dysfunction.  Also, it would be useful to obtain a baseline red blood cell magnesium level and to monitor that level as treatment proceeds.

Since MMFS-01 is not available, using Life Extension’s or other generic equivalents is reasonable.  Of course, ideally, some angel would fund a proper controlled study. But, as usual, that’s not likely to happen anytime soon.

If any readers decide to work with their doctors and try magnesium threonate, I and other readers would be grateful to learn whether or not it helped. In the absence of research funding the best way for us to learn which treatments help will be for each of us to report our personal anecodatal experience along to each other.  We look forward to your comments.