Less restrictive low-fat diet seen to lessen fatigue in MS: Pilot study

Patients allowed lean poultry, fish; adherence to plan was good

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by Steve Bryson, PhD |

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Adhering to a low-fat diet for three months was found to significantly ease fatigue among people with multiple sclerosis (MS), according to data from a pilot clinical trial.

The diet, which restricted total fat intake to less than 20% of calories per day, had a good adherence. Unlike other strictly plant-based low-fat diets, participants were allowed fat from lean animal protein sources, such as chicken, turkey, lean fish, and egg whites.

“A low-fat diet can truly make a difference in a patient’s fatigue level, even without going so far as to make it a vegan diet,” Vijayshree Yadav, MD, the study’s senior author and a professor of neurology at the Oregon Health & Science University (OHSU) School of Medicine, said in a university news story.

Overall, according to the researchers, “this 16-week pilot study of a diet intervention that included a significant reduction in saturated fat and increased carbohydrates and fiber calories appears to [lessen] fatigue in [people with] MS.”

The study, “A low-fat diet improves fatigue in multiple sclerosis: Results from a randomized controlled trial,” was published in the Multiple Sclerosis Journal.

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Earlier low-fat diet was found ‘too restrictive’ by patients

Fatigue is a common and disabling symptom of MS, a progressive disease characterized by inflammation and damage to healthy parts of the brain and spinal cord.

However, medications targeting MS-related fatigue have failed to show benefits. Meanwhile, several dietary interventions — including the Paleolithic, ketogenic, Mediterranean, and intermittent fasting diets — have generated mixed results on fatigue.

“Fatigue is very disabling for these patients,” said Yadav, who also serves as the director of the OHSU Multiple Sclerosis Center.

“There is no [U.S. Food and Drug Administration]-approved drug for fatigue, but we know that fatigue greatly affects their quality of life,” Yadav added.

Low-fat diets have been studied for weight loss and their benefits in people with cardiovascular disease. Such diets loosely have been defined as those with a saturated fat intake of less than 20 grams/day, or a total fat intake corresponding to less than 10% of daily calories.

Yadav and her colleagues recently showed that MS patients adhering to a very low-fat, plant-based diet reported significant improvements in fatigue and mood. Still, this dietary approach was “limited by many participants finding it too restrictive,” the researchers wrote.

That led the team to design a less restrictive low-fat diet — and now, to evaluate its impact on fatigue in a clinical trial (NCT03322982) involving 39 MS patients. The team noted difficulties in meeting the study’s target enrollment of more than 100 patients due to the COVID-19 pandemic and inadequate funding.

The participants’ mean age was 50, most were women (82%), and 92% were diagnosed with relapsing-remitting MS. Most (80%) were receiving disease-modifying therapies, and 11 were on medications for fatigue.

Following an initial or baseline visit, all participants underwent three random 24-hour diet recalls with a registered dietitian over the first two weeks. In these session, patients were asked to report their food intake during the previous 24 hours on two weekdays and one weekend day.

A total of 20 participants were then randomly assigned to either an active group or a control group. The active group received diet training between weeks two and four, and then followed the study diet between weeks four and 16. The control group followed their pre-study diet through week 16 and then received identical diet training at the study’s end.

“Exercise was not part of the program, meaning the study solely focused on diet as an intervention,” the news story noted.

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Reduction in fatigue was ‘significant’ in study’s active group

The dietary plan restricted participants’ total fat intake to less than 20% of calories per day, in addition to 20% of calories from protein and 60% from primarily complex carbohydrates. Participants were instructed to eat half of their dietary fat from protein sources such as chicken, turkey, lean fish, egg whites, tofu, and other soy products, and the remaining half from plant-based fats like avocados, olives, and nuts.

Saturated fats from animal products like red meat and dairy were restricted, and the amount of processed foods was minimized. Instead of these, patients were asked to focus on fruits, vegetables, whole grains, and lean protein, and limit fish oil or flax seed supplements, as well as vitamin B12, vitamin D, or other dietary supplements. All participants also underwent three additional 24-hour diet recalls at 16 weeks.

The study’s main goal was to determine the low fat diet’s impact on fatigue, as assessed with the Modified Fatigue Impact Scale (MFIS) questionnaire, in which higher scores reflect worse fatigue. Secondary goals included changes in diet composition and adherence to diet, as well as changes in fat biomarkers and in body weight.

Compared with the control group, those in the active group showed a reduction in fat calories — a 10.6% difference — over the study period, as well as an increase in carbohydrate calories (9.1% difference) and total fiber (8.2 grams difference). The protein calories remained unchanged between groups.

In the active group, the mean fat calorie intake dropped from 39% at baseline to 33% at week four, and to 24% by week eight, which remained stable until week 16. Overall, the mean fat calorie intake decreased by 15% in the active group versus 1% in the control group, “suggesting good adherence to the study diet,” the team noted.

At baseline, the mean MFIS score was 54 in both active and control groups. While fatigue was reduced after 16 weeks in both groups, that reduction was greater among patients in the active dietary group (14 vs. 10 points).

These differences were significant when only patients who strictly adhered to the low-fat diet were compared with the control group, where the dietary intervention was associated with an 8-point greater reduction in MFIS scores. Moreover, in another analysis in which five participants — two active, three controls — with extreme MFIS scores were excluded, the difference between active and control groups was 14 MFIS points.

Similar findings were observed when fatigue severity was assessed with the Fatigue Severity Scale (FSS). Active group participants also were significantly more active, showing increased physical activity over the study period compared with a decrease among controls. No differences were seen in measures of depression, disability, upper limb function, and walking abilities.

We demonstrated a significant reduction in fatigue with a low-fat dietary intervention in [people with] MS.

Finally, blood tests showed a that total cholesterol levels decreased by a mean of 12.9 mg per deciliter (mg/dL) in the active group, compared with an increase of 7.1 mg/dL in controls — a 20 mg/dL difference.

Likewise, mean low-density lipoprotein (LDL), the so-called bad cholesterol, was reduced with the low-fat diet while it increased in controls (−12.2 vs. 6.4 mg/dL). There were no changes in high-density lipoprotein (HDL), known as good cholesterol, or average blood sugar levels.

“You cannot really fudge the biomarkers,” Yadav said.

No safety concerns from lab tests were reported, except for an increase in MS symptoms among two active group patients. One of these participants reported increased fatigue between weeks four and 16.

“We demonstrated a significant reduction in fatigue with a low-fat dietary intervention in [people with] MS,” the researchers wrote.

“A larger multicenter study to validate findings across a more heterogeneous [varied] patient population and to increase external validity is being planned,” they added.