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”?

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.

Can the “MIND Diet” Reduce “Brain Fog” Due to Chronic Fatigue Syndrome and Fibromyalgia?

The short answer is we don’t know, because research on “brain

mediterranean diet vs mind diet
fruit, nuts and vegetables

fog” has been extremely limited–to say the least. (For specifics, see research by Anthony Ocon.)

 

Therefore, I hope our readers will be encouraged to learn that a relatively simple diet change is probably effective for reducing or delaying another currently “untreatable” form of brain fog—that due to Alzheimer’s Disease.

Diet fads versus Diet Science

For many decades we’ve faced an army of dietary fads. Each has claimed the ability to improve health. But, almost all claims are based mainly on anecdotes. Scientific studies have largely been absent. Fortunately, that’s changing.

Mediterranean Diet

The best research has focused on the “Mediterranean Diet” as a preventive treatment for heart disease and stroke. For this study, researchers recruited more than 7,000 Spanish men and women who were at high risk for heart disease or stroke. Each person was assigned to follow either the “Mediterranean Diet” plan (high in unsaturated fats such as olive oil and/or nuts, high in fruits, vegetables and whole grains, but low in saturated fat) or the “control” diet (the standard low fat diet such as the American Heart Association might advise).

The results showed that the Mediterranean Diet:

  • Had 30% fewer heart attacks and strokes compared to those on a low fat diet.
  • Is practical. People were able to follow it for more than 5 years.
  • Can help significantly within only 5 years.

These researches continued the study and applied neuro cognitive testing to 522 persons from within the main study. After six years, results further showed that the group on the Mediterranean Diet scored significantly higher in the cognitive testing compared to those in the low fat diet even after adjusting for risk factors.

Findings

The Mediterranean Diet, not only prevents heart attacks and stroke, but also helps maintain cognitive skills leading to the possibility of delaying or preventing the onset of Alzheimer’s dementia. But, since baseline cognitive scores were not measured, a true controlled study was still needed.

In 2015, Valls-Pedret and the Mediterranean Diet study group reported the results of a small controlled study that used 447 60+ year old Spanish volunteers who followed either a Mediterranean-style Diet or a low-fat diet. After 4.1 years, the results showed:

  • The Mediterranean Diet can reduce cognitive decline
  • Cognitive test and memory scores were higher for the Mediterranean Diet group compared to the low fat diet group

Further work on diet and Alzheimer’s comes from Martha Morris, Ph.D. and her research team at Chicago’s Rush University Medical Center. Dr. Morris’ team may be the world’s leading experts on the effects of nutrition on cognitive decline due to aging. She modified the Mediterranean diet to take into account other research on dementia and named it the MIND Diet. This was used in a study of 923 Chicago men and women, age 58 to 98. Each person did not have Alzheimer’s at the start of the study and their current eating pattern was scored against the key principles of the MIND Diet.

After 4.5 years, the following was found:

  • 144 of 923 (16%) were diagnosed with Alzheimer’s
  • Participants whose MIND Diet compliance scores were initially in the top third were only 47% as likely to develop Alzheimer’s compared to those in the bottom third
  • Those in the middle third did better than those in the lowest third, but not as well as those in the upper third
  • The Mediterranean Diet pattern also predicted a low Alzheimer’s rate but not quite as well as did high scores for the MIND Diet
  • A separate paper by Dr. Morris’s group reported the difference in cognitive skills between the top third on the MIND Diet and those in the bottom third were equivalent to the top third being “7.5 years younger in age” compared to the bottom third”—although chronologically in fact their average age was the same.

Take Home Thoughts

Evidence is increasing that the Mediterranean Diet, not only prevents heart attacks and stroke, but likely also helps maintain cognitive skills. We are not certain if the Mediterranean Diet would also help patients with brain fog due to ME/CFS or FM but we can probably reject as outdated the long-held “cliché it must be a “placebo effect” when people report that symptoms improve after a change in diet.

The strength of the MIND DIET study was that the statistical analysis was controlled for life style behaviors, illnesses and genetic risks for Alzheimer’s. However, researchers did not actively assign subjects to each diet. They simply scored how closely each subject’s self-chosen diet compared to the MIND Diet ideal. So, we can’t be sure whether high adherence to the MIND Diet caused the lower rate of Alzheimer’s or whether other factors might have been at work.

So, which diet should one follow if we have brain fog due to Fibromyalgia (FMS) or Chronic Fatigue Syndrome (CFS)? At this time, we have no easy answer. Ideally, someone would fund a study where patients with CFS or Fibromyalgia would take a cognitive test, then go on either the MIND Diet (or Mediterranean Diet) or their usual way of eating. (Readers who have major wealth, might consider this project!) Aside from this, people who adopt the MIND Diet or the Mediterranean on their own, can report their experience to their doctors to our blog and/or to a widely read health support website such as Prohealth.com.

For those interested in the Mediterranean Diet, consider a book by Nick Nigro and Bay Ewald, Living the Mediterranean Diet: Proven Principles and Modern Recipes for Staying Healthy. See links for a brief summary of the MIND Diet and a more detailed summary in pdf format.

For either diet, plan on a minimum 3 to 6 month trial before judging it’s effects.
We welcome comments from any patient or doctor who has useful information to share about diets in this context.