March 2, 2016

Single Dose Multivitamin Improves Mood

Supplement improves mood within 1 hour, but why?
The surprising results of this study—that giving a multivitamin and mineral supplement caused acute mood improvement in just 1 hour—made us want to dig deeper.


Macpherson H, Rowsell R, Cox KHM, Scholey A, Pipingas A. Acute mood but not cognitive improvements following administration of a single multivitamin and mineral supplement in healthy women aged 50 and above: a randomised controlled trial. Age (Dordrecht, Netherlands). 2015;37(3):9782. 


Double blind, placebo-controlled, randomized trial


Seventy-six women between 50 and 75 years old. The intervention group included 39 and the placebo group included 37. Exclusion criteria included smoking, diabetes, cardiovascular disease, dementia, stroke, head trauma, alcohol abuse, clinically diagnosed anxiety, depression, and psychiatric disorders.
Participants were excluded if they were taking “anti-depressant medication, anti-anxiety medication, high-dose anti-coagulants, anti-cholinergic drugs or acetylcholinesterase inhibitors. … Participants were required to abstain from supplementation with vitamin E, multivitamins, B vitamin complex, gingko biloba, fish oil, and St John’s Wort for 4 weeks preceding the study visit.”


Oral multivitamin mineral herbal (MVMH) tablet (Swisse Women’s 50+ Ultivite) or matching placebo. The MVMH contained folic acid; vitamins A, B1, B2, B5, B6, B12, C, E, and zinc at recommended daily intake (RDI) amounts. It also contained B3, D3, calcium, and magnesium below the RDI, as well as 18 herbs and 3 strains of probiotics. A complete listing of the contents and their doses can be found at the company’s website.1
Mood was assessed before and after completing a cognitive battery test for cognition. The participant then consumed either MVMH or placebo. One hour after this dose was consumed the mood was again assessed before and after a cognitive battery test. 
Outcome Measures: Acute multivitamin (MVMH) effects on cognition and mood were determined 1-2 hours after taking placebo or MVMH. All outcomes were secondary outcomes from the Behavioral Effects of Multivitamin Supplements study, which was a 4-week study.
The Depression and Anxiety Stress scale (DASS), the State Anxiety Scale (SAS), the Bond-Lader mood/visual analogue scales (VAS) for stress, anxiety, concentration, physical fatigue, and mental fatigue were used.
Cognition was assessed using the Swinburne University computerized cognitive battery (SUCCAB) stimuli.

Key Findings

Mood: There was a significant reduction in the DASS score after intervention in the MVMH group, but not in the placebo group (P=0.001). There was also greater calmness as measured by the VAS in the MVMH (P=0.003). Only the MVMH group had a significant reduction in VAS stress rating (P=0.001). Anxiety reduction did not reach statistical significance for either group.
Cognition: There were no significant differences in cognitive measures in either group. 


There have been many studies suggesting that multivitamin mineral (MVM) usage may improve mood and/or cognition. These studies have specifically assessed the use of MVM over 4 weeks or more. The current study under review is most intriguing for the immediacy of its effect on mood parameters. It is surprising that a single dose of a MVM could have a measurable effect at all on mood.
Effects of B vitamins on stress and mood have been researched in longer term trials, and most of these trials have suggested benefit.2–5 B vitamins play a central role in neurotransmitter regulation both directly in their synthesis as well as indirectly through the influence of S-adenosyl methionine (SAMe). Depression has been linked to deficiencies in B vitamins, especially B12 and folate.6
B vitamins play a central role in neurotransmitter regulation both directly and indirectly.
Additional nutrient deficiencies may also contribute to mood disturbances and cognitive difficulties. Vitamin D deficiency is associated with low mood as well as cognitive dysfunction in the elderly.7 Zinc deficiency is associated with depression specifically.8 At least 5 studies have shown that low selenium and “poorer mood” are linked.9 It is possible that a MVM can replete those who are otherwise deficient in any given nutrient of the supplement used. Such repletion is expected to lead to improved mood, but how can it have an effect in just 1 hour?
The authors of the current study admit there is no explanation yet for such immediate effects the MVMH on stress or mood. However, they do offer possible theories. It is possible that the MVMH causes acute improvements in vascular endothelial function, allowing for better oxygen and nutrient delivery to the brain. It is also possible that mitochondrial function improves within 1 hour of consumption. Peak levels of nutrients, such as folate, are seen only 1 to 2 hours after ingestion, leading the authors to assert that assessing changes in brain function at peak circulation points is not without reason. 
The most plausible explanation, not emphasized by the authors, is that the immediate effect of the MVMH combination on mood is due to the herbs it contains, not the nutrients. There were 18 herbs all in the form of concentrated extracts. Some extracts were the equivalent to between 0.5 and 1.5 grams of dried herb. Some were classic “tonifying” herbs such as hawthorne, bilberry, and St. Mary’s thistle. Others could be acting as mild blood thinners, among their many actions (turmeric, gingko, grape seed extract.) Two herbs in particular, skullcap (Scutellaria lactiflora) and withania (Withania somnifera) would be expected to have calming effects acutely when taken. Simply put, the publication’s title is misleading. Most MVM supplements do not contain 18 herbal concentrates. 
This publication is a good reminder. As clinicians, we often do not have time to delve into the Methods section of publications. However, when the findings are surprising, run counter to a given paradigm, or seem to stand out for any reason, perhaps we should remember to parse out the details. 
One last note: The current study did not demonstrate any benefit to cognition. Other studies have suggested benefit to cognition with a MVM over longer periods of time.10–12 Since MVM of any kind are typically taken daily for extended periods of time, whether it works acutely for cognition is more of an academic question than a clinically relevant one. 

Categorized Under


  1. Swisse - Swisse Women’s Ultivite 50+ | Women's Health | Vitamins & Supplements. Accessed February 25, 2016.
  2. Carroll D, Ring C, Suter M, Willemsen G. The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological well-being in healthy young male volunteers: a double-blind placebo-controlled trial. Psychopharmacology (Berl). 2000;150(2):220-225. 
  3. Kennedy DO, Veasey R, Watson A, et al. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl). 2010;211(1):55-68. 
  4. Schlebusch L, Bosch BA, Polglase G, Kleinschmidt I, Pillay BJ, Cassimjee MH. A double-blind, placebo-controlled, double-centre study of the effects of an oral multivitamin-mineral combination on stress. S Afr Med J. 2000;90(12):1216-1223. 
  5. Stough C, Scholey A, Lloyd J, Spong J, Myers S, Downey LA. The effect of 90?day administration of a high dose vitamin B-complex on work stress. Hum Psychopharmacol. 2011;26(7):470-476. 
  6. Alpert JE, Mischoulon D, Nierenberg AA, Fava M. Nutrition and depression: focus on folate. Nutrition. 2000;16(7-8):544-546. 
  7. Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006;14(12):1032-1040. 
  8. Levenson CW. Zinc: The New Antidepressant? Nutr Rev. 2006;64(1):39-42. 
  9. Benton D. Selenium Intake, Mood and Other Aspects of Psychological Functioning. Nutr Neurosci. September 2013. Accessed February 24, 2016.
  10. Harris E, Macpherson H, Vitetta L, Kirk J, Sali A, Pipingas A. Effects of a multivitamin, mineral and herbal supplement on cognition and blood biomarkers in older men: a randomised, placebo-controlled trial. Hum Psychopharmacol. 2012;27(4):370-377. 
  11. Summers WK, Martin RL, Cunningham M, DeBoynton VL, Marsh GM. Complex antioxidant blend improves memory in community-dwelling seniors. J Alzheimers Dis. 2010;19(2):429-439. 
  12. Macpherson H, Ellis KA, Sali A, Pipingas A. Memory improvements in elderly women following 16 weeks treatment with a combined multivitamin, mineral and herbal supplement: A randomized controlled trial. Psychopharmacology (Berl). 2012;220(2):351-365.