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?

Psychotherapy for ME/CFS Does Not Help Fatigue (much)

option 3
psychotherapy for ME/CFS

Background
In the U.S., few physicians or scientists still believe that ME/CFS is mostly “all in your mind”. At last, the National Institutes of Health (NIH) has also come on board. NIH has charged the National Institute of Neurological Disorders and Stroke with the (not yet budgeted) task of advancing research on ME/CFS. But, in Europe, influential elements remain committed to the view that ME/CFS is mainly a problem of psychological distress. This stress, they argue, causes people to become inactive. Inactivity then causes physical deconditioning—much like the astronaut who can barely stand up when she first returns from space.

The PACE Study
Sadly, promoting this “psychosomatic” view tends to discourage research institutions, aspiring scientists, drug companies and philanthropies from committing to research toward understand our illness.  The PACE study, done in England, is often cited to justify the “all in your mind” hypothesis.  This study created three groups of patients with a chronic fatigue like illness. The researchers gave patients in one group a cognitive behavioral psychotherapy program. A second group did a gradually graded exercise program. The control group had no exercise or psychotherapy program. Instead they were treated by physicians who were said to specialize in ME/CFS but did not receive psychotherapy or graded exercise.

Issues with PACE
The PACE study has flaws.  Some of these flaws could undermine the study’s conclusions. For example, it’s not at all clear that all the study subjects actually had what we would agree is either ME or CFS. Serious questions have been raised as to potential bias in how the authors’ decided which patients had improved and which patients had not. Nor is the claimed degree of improvement anywhere close to what one might view as a “cure”.   But, even more troublesome is the false extrapolation from the PACE data that people who should know better have made—even if the study’s reported results were perfectly correct.

Cognitive behavioral therapy is a useful technique to help train people into the habit of positive thinking. Basically, this means seeing the glass as half full instead of half empty. Cognitive therapy has been shown to help people cope better with many different forms of indisputably physical health problems including heart disease, cancer, rheumatoid arthritis and others. Similarly, carefully monitored exercise reconditioning, if done within a patient’s limits, can modestly help people with physical illness of many types somewhat improve how they feel and function.

What’s mischievous about how the PACE study has been used is that by implying that better coping through psychological support and/or reconditioning is the answer gives the impression that the illness involved is substantially psychosomatic. No one would claim that for a patient with angina, emphysema, rheumatoid arthritis or cancer. Why assign that blame to patients with ME/CFS? But, since PACE study-related debate continues, it might be refreshing to review a study, also from England, where a psychological intervention for chronic fatigue indisputably FAILED.

Contradictory Study
298 patients with long term chronic fatigue (not clearly defined as ME/CFS) received either one of two forms of psychological counseling—“pragmatic rehabilitation” or “supportive listening”. The “control group” had routine treatment with their general practitioner.  The “pragmatic rehabilitation” therapy taught patients about physical deconditioning, coping with anxiety, improving sleep and “overcoming impediments to change”. “Supportive listening” focused on “creating an emotional and physical environment conducive to helping relationship”.

Researchers scored each patient’s fatigue and related symptoms, using the Chalder fatigue scale (an 11 questions survey asking about people’s symptoms and activities) at entry, after 20 weeks and then again about a year later.  After 20 weeks the average score in all three groups improved but only modestly. Scores in the pragmatic rehabilitation group were modestly better than either the “supportive listening” or the general practitioner groups. At 20 weeks the advantage to pragmatic rehabilitation was statistically significant.  But, by 70 weeks no further improvement had occurred in any of the 3 groups. And the difference between pragmatic rehabilitation treatment and the general practitioner group was no longer statistically significant. Basically, the two different forms of behavioral/psychological counseling had at best a very modest short term impact on the severity of illness. Over the long run the psychological component had no meaningful impact.

Take Away Thoughts
Why is this important? So as long as those who matter believe ME/CFS is mainly “all in your mind”, everyone suffers—patients, their families, aspiring scientists, health care budgets and society in general. (Well maybe not the disability insurance companies.)  But our patients’ battle is far from won even in the USA.

NIH has committed itself to look seriously at ME/CFS. But, no increase in budget has yet been set. Please recall this. For 2015 and 2016 NIH budgeted only about $5 million a year to study ME/CFS, while the Centers for Disease Control estimates that more than one million Americans suffer from chronic fatigue syndrome. In contrast, an estimated 400,000 Americans have Multiple Sclerosis. NIH’s budget for MS? About $98 million a year. This isn’t a knock against MS research; just a comparison.

NIH has not yet committed to a new and presumably higher budget for ME/CFS. As all such decisions reflect a mix of political and scientific issues, those among us who have any credibility with federal legislators or bureaucrats—this might be a good time to employ some of our clout.

We welcome any comments you have especially your experiences with psychological counseling.  Thank you.

 

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.