How Hedonia Works

Omega-3 Fatty Acids

Numerous studies confirm the association between low levels of omega-3 and depression. These findings are demonstrated in a meta-analysis of 14 studies published in 2010 showing low plasma levels of EPA and DHA in depression.1

Though there is no definition of a normal intake of omega-3 fatty acids, The National Academy of Medicine (formerly the Institute of Medicine) recommends 160mg/day for men and 110mg/day for women for the combined intake of both fatty acids.2 The 2015-2020 Dietary Guidelines for Americans (DGA) recommends levels of seafood intake giving approximately 250mg of EPA and DHA daily, it seems that those with depression may have a specific need for more omega-3 fatty acids. EPA in particular has a role in regulating neuroinflammation known to be a component of depression and higher levels of EPA intake are associated with normalisation of depression.3-7 International guidelines are consistent in their recommendations of higher levels of EPA than recommended for the general population. Those with depression should be taking 1-2g of EPA with an oil where EPA is at least in a 2:1 ratio with DHA.8-10 Hedonia provides 500mg of EPA per capsule and with a 4-capsule daily recommendation, meets the nutritional needs of those with depression.

Supplemental EPA is recommended for people with depression in 3 clinical guidelines.8-10

100 studies since 1989 support the use of omega-3 in depression (assessed by GOED in the GOED clinical database).11

Hedonia corrects OMEGA-3 deficiency

The average consumption of omega-3 (EPA and DHA) in food is well below the recommended value.
Guidelines for depression recommend increased intake of EPA from 1-2g daily.

Data from Bottiglieri, et al (1990). J Neurol Neurosurg Psychiatry, 53(12), 1096-1098.


  1. Lin, P.Y., S.Y. Huang, and K.P. Su, A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biol Psychiatry, 2010. 68(2): p. 140-7.
  2. Trumbo, P., et al., Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc, 2002. 102(11): p. 1621-30.
  3. Nishi, D., et al., Plasma estradiol levels and antidepressant effects of omega-3 fatty acids in pregnant women. Brain Behav Immun, 2020. 85: p. 29-34.
  4. Parletta, N., et al., A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutr Neurosci, 2019. 22(7): p. 474-487.
  5. Amini, M., et al., The effects of fish oil omega-3 fatty acid supplementation on mental health parameters and metabolic status of patients with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. J Psychosom Obstet Gynaecol, 2018: p. 1-9.
  6. Jiang, W., et al., Long-Chain Omega-3 Fatty Acid Supplements in Depressed Heart Failure Patients: Results of the OCEAN Trial. JACC Heart Fail, 2018. 6(10): p. 833-843.
  7. Keshavarz, S.A., et al., Omega-3 supplementation effects on body weight and depression among dieter women with co-morbidity of depression and obesity compared with the placebo: A randomized clinical trial. Clin Nutr ESPEN, 2018. 25: p. 37-43.
  8. Guu, T.W., et al., International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder. Psychother Psychosom, 2019. 88(5): p. 263-273.
  9. Chang, J.P. and K.P. Su, Nutritional Neuroscience as Mainstream of Psychiatry: The Evidence- Based Treatment Guidelines for Using Omega-3 Fatty Acids as a New Treatment for Psychiatric Disorders in Children and Adolescents. Clin Psychopharmacol Neurosci, 2020. 18(4): p. 469-483.
  10. Sarris, J., et al., Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. World J Biol Psychiatry, 2022: p. 1-32.
  11. Bernasconi, A.A., et al., Development of a novel database to review and assess the clinical effects of EPA and DHA omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids, 2022. 183: p. 102458.


Folate is an important nutrient acting as the starting point for several neurotransmitters in the brain. Research into folate has shown mixed results and this is due to many people having an error in the enzyme system that metabolizes folate. This enzyme is called MTHFR which is the short name for the enzyme methyleneltetrahydrofolate reductase. Natural variations in the DNA coding for the protein, called polymorphisms, can lead to less activity in the protein. MTHFR converts folate to L-methylfolate which is important since only L-methylfolate can enter the brain. Therefore, methylfolate is often called the “active” form of folate.

Some polymorphisms of MTFHR lead to less conversion of folate to L-methylfolate, which means less enters the brain leading to a deficiency. Studies have confirmed that people with polymorphisms in the MTFHR gene have a higher risk of depression.1 L-Methylfolate has a number of actions in the brain including the generation of neurotransmitters such as serotonin and dopamine.2 A deficiency in folate and L-methylfolate can therefore contribute to depression and numerous studies support this.3, 4 Taking L-methylfolate orally can help re-address this imbalance and or deficiency which has been clinically demonstrated to be important for depression.

Hedonia provides 20mg of L-methylfolate in accordance with guideline recommendations.

16 studies support the use of L-methylfolate in people with depression.

Supplemental L-methylfolate is recommended for people with depression in the international clinical guideline Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce

MTHFR gene in depression

*Gilbody, S., Lewis, S., & Lightfoot, T. (2007). Am J Epidemiol, 165(1), 1-13.

MTHFR is a protein that converts folate to L-methylfolate. Natural variations in the protein MTHFR can lead to reduced protein activity[1] and less conversion of folate to L-methylfolate. People with certain variations in the MTHFR have a higher risk of depression [2]. L-Methylfolate has important activity in the brain including the generation of neurotransmitters [3]. Taking L-methylfolate orally can help re-address this imbalance and or deficiency created by the MTHFR variant and nutritional studies support the role of supplementation in depression.


  1. Kelly, C.B., et al., The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol, 2004. 18(4): p. 567-71.
  2. Stahl, S.M., L-methylfolate: a vitamin for your monoamines. J Clin Psychiatry, 2008. 69(9): p. 1352-3.
  3. Morris, M.S., et al., Depression and folate status in the US Population. Psychother Psychosom, 2003. 72(2): p. 80-7.
  4. Farah, A., The role of L-methylfolate in depressive disorders. CNS Spectr, 2009. 14(1 Suppl 2): p. 2-7.

SAMe - S-adenosyl Methionine

S-adenosyl methionine, also known as SAMe, is an amino acid produced by the body. It plays an essential role in a number of biological pathways. One important action is in the generation of neurotransmitters such as dopamine and serotonin, which play a vital role in mood and depression. SAMe is produced during folate metabolism and low levels of the enzyme that makes SAMe is associated with depression.1 Lower levels of SAMe have also been demonstrated in people with depression. Importantly, giving SAMe orally increases the levels of SAMe in the cerebrospinal fluid back to normal levels.2

Separate studies have shown that depression is associated with a decrease in SAMe, which can be restored by supplementation with 1600mg SAMe daily.2, 3 Supplementation with SAMe has been demonstrated to be associated with normalisation of depression.4, 5 Hedonia provides 1600mg of SAMe to correct the deficiency of SAMe associated with depression.

Supplemental SAMe is recommended for people with depression in an international clinical guideline: Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce

8 studies since 2010 show the efficacy of SAMe in people with depression.

Hedonia corrects SAMe deficiency

SAMe levels in healthy and depressive adults.
In a separate study supplementation with SAMe restores levels to those seen in healthy individuals

Data from Bottiglieri, et al (1990). J Neurol Neurosurg Psychiatry, 53(12), 1096-1098.


  1. Mischoulon, D. and M. Fava, Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr, 2002. 76(5): p. 1158s-61s.
  2. Bottiglieri, T., et al., Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry, 1990. 53(12): p. 1096-8.
  3. Mischoulon, D., et al., Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder. J Clin Psychiatry, 2012. 73(6): p. 843-8.
  4. Papakostas, G.I., et al., S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry, 2010. 167(8): p. 942-8.
  5. Alpert, J.E., et al., S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. J Clin Psychopharmacol, 2004. 24(6): p. 661-4.

Hedonia® is classified (and regulated) in the USA as a medical food product.

Hedonia is intended to be used under medical supervision alongside an individual’s physician-directed treatment.

Each gel-capsule contains a total omega-3 triglyceride content of 640mg of which EPA is 400mg, 400mg of Adonat® Premium SAMe Stabilized PowdeR, and 3.75mg of Quatrefolic® ((6S)-5-methyltetrahydrofolic acid).


Mono and diglycerides of fatty acids, Lemon natural flavor, sunflower lecithin, gelatin, Firming agent: glycerol, colorant: Titanium dioxide, Coloring: allura red, yellow-orange, and brilliant blue FCF