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Omega-3s and Vitamin D Boost Key Mood Chemical
Findings help explain why fish-rich diets can ease or deter mental disorders 03/18/2015 By Craig Weatherby

The first links between omega-3s and key brain chemicals were seen 17 years ago.

Pioneering NIH clinical psychiatrist Joe Hibbeln, M.D. made this critical finding back in 1998.

Hibbeln's team showed that people with higher blood levels of omega-3s also had more of two key mood-related chemicals in their spinal fluid: dopamine and serotonin.
Serotonin is a hormone-like “neurotransmitter” believed to influence a wide variety of brain and body functions.
It plays a key role in the brain and central nervous system, and in many other body functions … particularly in the gut.
As a brain chemical, serotonin affects mood, decision-making, social behavior, aggression, impulsive behavior, and more.
Serotonin and mental health
Low brain-serotonin levels feature in mental disorders from depression, autism spectrum disorders, and attention deficit disorders, to bipolar disorder and schizophrenia.
As to depression, it’s unclear whether low serotonin causes it, or whether depression lowers serotonin levels.
Fish fit the vitamin D bill; Sockeye salmon stand out
Supplements offer an easy way to get ample doses of vitamin D.
But whole foods are the best source ... and certain fatty fish abound in vitamin D, far outranking milk and other D-fortified foods.
Wild sockeye salmon ranks as the richest source, with a single 3.5-oz. serving surpassing the US RDA of 600 IU by about 15 percent:
IUs of Vitamin D
per 3.5-oz. serving*
Sockeye salmon 687
Albacore tuna 544
Silver salmon 430
King salmon 236
Sardines 222
Sablefish 169
Halibut 162
*Click here for our full test results.
The leading antidepressants – called selective serotonin reuptake inhibitors (SSRIs) – help maintain higher levels of serotonin in the blood.
But scientists remain unsure whether that is why SSRI drugs ease depression, or whether they work by promoting connections between brain cells (neurons), as they are known to do.
Vitamin D and omega-3s in mental health
Vitamin D and seafood-source omega-3s seem to improve cognitive function and behavior in certain brain disorders ... see the Omega-3s & Brain Health and Vitamin D & Brain Health sections of our news archive.
However, the underlying reasons for their apparent brain benefits have been unclear.
Like SSRI drugs, seafood-source omega-3s promote stronger and more numerous networks between the brain’s neurons, but without side effects … see Omega-3s Boost Brain Networks Critical to Memory Capacity.
(Of the two key omega-3s found in seafood and humans – DHA and EPA – DHA is the most important to brain networks, functions, structure, and overall health.)
Omega-3s also boost the function of brain-cell receptors for glutamate, a neurotransmitter critical to brain “neuro-plasticity” … a vital capacity that’s typically impaired in mental disorders: see New Insight into Anti-Aging Brain Benefits of Omega-3s.
Now, California-based researchers report that the influence of vitamin D and omega-3s on brain serotonin levels may further explain why these nutrients appear to help deter or alleviate diverse brain disorders.
Study ties vitamin D and seafood-source omega-3s to serotonin levels
The new paper comes from world-renowned biochemist Bruce Ames, Ph.D., and Rhonda Patrick, Ph.D., his colleague at UCSF Benioff Children's Hospital in Oakland (Patrick RP, Ames BN 2015).
“In this paper we explain how serotonin is a critical modulator of executive function, impulse control, sensory gating, and pro-social behavior,” says Dr. Patrick.
“We link serotonin production and function to vitamin D and omega-3 fatty acids, suggesting one way these important micronutrients help the brain function and affect the way we behave.” (UCSF 2015)
Last year, Patrick and Ames reported that vitamin D regulates the conversion of the amino acid tryptophan into serotonin (Patrick RP, Ames BN 2014).
In their new paper, the pair note that omega-3 EPA suppresses release of messenger molecules (E2 prostaglandins) that promote inflammation and reduce release of serotonin in the brain.
And they point out that omega-3 DHA makes various serotonin receptors more accessible to serotonin by increasing cell-membrane fluidity in key neurons.
Their new paper also illuminates how low body levels of vitamin D and omega-3s impair genetic pathways – including the serotonin pathway – important to brain development, social behavior, and decision making.
According to professor Ames, “Vitamin D, which is converted to a steroid hormone that controls about 1,000 genes, many in the brain, is a major deficiency in the US … and omega-3 fatty acid deficiencies are very common because people don’t eat enough fish.” (UCSF 2015)
Professors Ames and Patrick suggest that higher intakes of vitamin D and seafood-source omega-3s (EPA and DHA) would optimize brain serotonin levels and function.
Accordingly, they also believe that higher intakes of vitamin D and omega-3s may help prevent and ameliorate some of the symptoms associated with major mental disorders … without side effects.
Six years ago, researchers from the University of Colorado’s School of Medicine noted a marked drop in Americans’ vitamin D levels from 1988 to 2004.
As they said, “Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.” (Ginde AA et al. 2009)
And few American get the 250-500mg of omega-3s per day recommended by public health agencies worldwide (see our Omega-3 Facts & Sources page). 
Fatty wild fish such as salmon, tuna, sardines, sablefish, and anchovies are the best food sources of both of these essential nutrients, by far.
  • Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009 Mar 23;169(6):626-32. doi: 10.1001/archinternmed.2008.604.
  • Hibbeln JR, Ferguson TA, Blasbalg TL. Omega-3 fatty acid deficiencies in neurodevelopment, aggression and autonomic dysregulation: opportunities for intervention. Int Rev Psychiatry. 2006 Apr;18(2):107-18. Review.
  • Hibbeln JR, Linnoila M, Umhau JC, Rawlings R, George DT, Salem N Jr. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry 1998; 44: 235-242.
  • Hibbeln JR, Umhau JC, Linnoila M, George DT, Ragan PW, Shoaf SE, Vaughan MR, Rawlings R, Salem N Jr. A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids. Biol Psychiatry. 1998 Aug 15;44(4):243-9.
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  • Patrick RP, Ames BN. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar, schizophrenia, and impulsive behavior. FASEB J. 2015 Feb 24. pii: fj.14-268342. [Epub ahead of print] Review. doi: 10.1096/fj.14-268342. Accessed at
  • Patrick RP, Ames BN. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J. 2014 Jun;28(6):2398-413. doi: 10.1096/fj.13-246546. Epub 2014 Feb 20. Review.
  • Singh RB, Gupta S, Dherange P, De Meester F, Wilczynska A, Alam SE, Pella D, Wilson DW. Metabolic syndrome: a brain disease. Can J Physiol Pharmacol. 2012 Sep;90(9):1171-83. doi: 10.1139/y2012-122. Epub 2012 Aug 22. Review.
  • Sublette ME, Galfalvy HC, Hibbeln JR, Keilp JG, Malone KM, Oquendo MA, Mann JJ. Polyunsaturated fatty acid associations with dopaminergic indices in major depressive disorder. Int J Neuropsychopharmacol. 2014 Mar;17(3):383-91. doi: 10.1017/S1461145713001399. Epub 2013 Dec 3.
  • UCSF Benioff Children's Hospital Oakland (UCSF). Omega-3 Fatty Acids and Vitamin D May Control Brain Serotonin, Affecting Behavior and Psychiatric Disorders. February 5, 2015. Accessed at
  • Young BE, McNanley TJ, Cooper EM, McIntyre AW, Witter F, Harris ZL, O'Brien KO. Vitamin D insufficiency is prevalent and vitamin D is inversely associated with parathyroid hormone and calcitriol in pregnant adolescents. J Bone Miner Res. 2012 Jan;27(1):177-86. doi: 10.1002/jbmr.526.