Low Magnesium and Folate Intake Correlates with Multiple Sclerosis Fatigue, New Study Shows

Patient Expert

Proper nutrition is important in providing our bodies with the building blocks necessary to promote health and prevent disease.   A recent study in Iran investigated the relationship between nutritional status (dietary intake of nutrients) and its relationship with fatigue in MS patients.   Researchers have found that diets which are lower in magnesium and folate are correlated with higher fatigue scores in MS patients (Bitarafan 2014).

Fatigue is one of the most common symptoms affecting 75-90% of people living with MS while up to 50% of MS patients indicate fatigue as one of their worst problems (Forwell 2008).   Although the cause of MS fatigue is not fully understood, inflammatory cytokines, axonal atrophy, hypometabolism of specific brain regions, and higher energy requirement are recognized as possible contributing factors (Bitarafan 2014).   In patients with chronic fatigue syndrome (CFS), research indicates that fatigue may be worsened by an imbalanced diet (Cox 1991; Werbach 2000).

Between 2010 and 2012, researchers enrolled 101 relapsing-remitting MS patients (75% female; aged 20-40; mean EDSS   1.02 ± 0.99; mean BMI 24.21 ± 3.79 kg/m2 ; relapse-free in 3 months prior to study) in a cross-sectional study conducted at the Iranian Center of Neurological Research in Tehran, Iran.   Participants completed a 3-day food questionnaire used to determine dietary intake of various nutrients (macronutrients and micronutrients).   A dietitian compared the results to dietary reference intake (DRI) values, including recommended dietary allowance (RDA), adequate intake (AI), and tolerable upper intake (UL).   Fatigue was assessed using a Persian version of the Modified Fatigue Impact Scale (MFIS), a 21-item questionnaire that measures the effect of fatigue in terms of physical, cognitive, and psychosocial functioning.

Nutritional status of MS patients

Results of this study showed that mean daily energy intake (1965.56 ± 320.98 kcal/day) and percentage of total daily energy provided by carbohydrates (56.1%), proteins (12.2%), and fats (31.7%) were in accordance with DRI.   Daily energy intake from fat consisted of saturated fatty acid (8.82%), monounsaturated fatty acid (12.24%), and polyunsaturated fatty acid (10.64%), also consistent with daily recommendations.   However, mean fiber intake was significantly below recommendations at 14.17 ± 3.71 grams in men, and 14.69 ± 4.59 grams in women.   The amount of fiber intake in this study represented only 37.28% and 58.76% of the daily recommendations for fiber for men and women, respectively.

Daily dietary intakes of vitamin D, folate, calcium, and magnesium were significantly lower than DRI as well. In men, zinc was significantly lower but iron was higher than DRI. In women, iron intake was significantly below DRI levels. Researchers have previously demonstrated that low calcium and iron intake may be correlated with progression of MS (Ramsaransing 2009).   In addition, deficiencies in vitamin D and magnesium have been implicated as risk factors for MS (Pennington 1997; Yasui 1992).

Fatigue and nutrient deficiencies

In the current study, only the nutrients, folate and magnesium, were associated with increased fatigue.   Researchers found that lower dietary intake of magnesium and folate in MS patients is significantly correlated with higher Modified Fatigue Impact Scale (MFIS) scores, specifically the physical subscale.   Fatigue scores were not significantly associated with vitamin D and calcium intake.

In patients with chronic fatigue syndrome (which is similar to, but not identical to MS fatigue), supplementation with magnesium and folate have been shown to improve symptoms when deficiencies are detected (Werbach 2000; Godfrey 1990; Jacobson 1993).   At least one MS study has found that the concentration of magnesium in the central nervous system is lower in MS patients than healthy controls (Yasui 1992).

Correcting deficiencies

Unfortunately, there are limitations to the current study.   Researchers did not measure the serum levels of the studied nutrients, nor did they compare dietary intakes of MS patients with a healthy control group.   Caution should be taken in interpreting the data.   However, it could be suggested that MS patients who experience high levels of physical fatigue may consider examining their nutritional intake to detect deficiencies, according to DRI values, and to correct those deficiencies, especially with regard to folate and magnesium.

Foods which are high in magnesium include raw spinach, squash and pumpkin seeds, soy beans, fish (mackerel), brown rice, avocados, plain non-fat yogurt, bananas, dried figs, and dark chocolate.   Foods high in folate include raw spinach, black eyed peas, lentils, asparagus, romaine lettuce, avocado, broccoli, mango, oranges, and wheat bread.

Would you be willing to independently undertake the effort to study your own nutritional intakes and take note of any effect on specific MS symptoms you may have, including fatigue?   The results would be interesting.


Bitarafan S, Harirchian MH, Nafissi Sh, et al. Dietary intake of nutrients and its correlation with fatigue in multiple sclerosis patients. Iran J Neurol. 2014;13(1):28-32.

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Forwell SJ, Brunham S, Tremlett H, et al. Primary and Nonprimary Fatigue in Multiple Sclerosis. Int J MS Care. 2008;10:14-20.

Pennington CR. Disease and malnutrition in British hospitals. Proc Nutr Soc. 1997;56(1B): 393-407.

Ramsaransing GS, Mellema SA, De Keyser J. Dietary patterns in clinical subtypes of multiple sclerosis: an exploratory study. Nutr J. 2009;8:36.

Schwarz S, Leweling H. Multiple sclerosis and nutrition. Mult Scler. 2005;11(1):24-32.

Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev. 2000;5(2):93-108.

Yasui M, Ota K. Experimental and clinical studies on dysregulation of magnesium metabolism and the aetiopathogenesis of multiple sclerosis. Magnes Res. 1992;5(4):295-302.