Get in the mood for nutrients

Many nutrients, herbals and other supplements have been linked to improvements in mood and cognitive function — from stress and anxiety to depression and dementia. Paul Clayton, PhD, investigates

A number of studies suggest that taking B vitamins may produce improvements in mood as well as cognitive function.1 Studies indicate that increased intake of thiamine (vitamin B1) provides cognitive benefits, including increased reaction times.2,3 Work has also been done on the co-enzyme form of niacin (vitamin B3) known as nicotinamide adenine dinucleotide (NADH). A small number of short-term studies done with NADH have shown that it has slight to moderate benefits for depression, Parkinson's, Alzheimer's and chronic fatigue syndrome.4,5,6,7

Homocysteine, a derivative of the amino acid methionine, has been identified as an important risk factor in both heart disease and age-related cognitive decline.8,9 It has been shown that adequate intakes of folic acid, and vitamins B6 and B12 help to ensure that homocysteine levels are kept low.10 One study investigated the relationship between blood concentrations of homocysteine, vitamins B12 and B6, and folate, and the cognitive performance of 70 male subjects aged between 54 and 81.11 Lower concentrations of vitamin B12 and folate, and higher concentrations of homocysteine, were associated with poorer memory.

S-adenysyl-methionine (SAMe), a compound made from methionine, is a methyl donor involved in the synthesis of dozens of important compounds in the body. It has been suggested that SAMe supplementation may also help in the metabolism of folate and vitamin B12, and thus alleviate such conditions as depression.12 Another methyl donor, dimethyl-amino-ethanol (DMAE), has been shown to help improve mood and motivation in older patients with dementia, though studies show limited impact on memory.13,14,15

Polyunsaturated fatty acids
Around 60 per cent of the brain consists of lipids that make up the cell membrane of every brain cell. The types of fats present in the brain influence the fluidity of the cell membrane, and thus how well brain cells interact and communicate. The fats that make up brain-cell membranes are much more resistant to changes in diet than the fats forming the cell membranes of other tissues in the body. The brain is, for example, able to preserve its fatty composition despite shortages of essential fats in the diet. However, animal studies show it is possible to alter the fat content of the brain through diet.16

Building on this foundation, epidemiological studies suggest that differing types of fat in the diet may be linked to mental state. One study compared fish consumption and rates of depression in a number of countries, and concluded that there is a link between increasing rates of depression, the consumption of increased amounts of saturated fatty acids and omega-6 fatty acids, and the decreased consumption of omega-3 fatty acids found in fish.17 (See the Fi exclusive interview with innovative supplier EPAX.)

Other phospholipids
Phosphatidylcholine (PC) is the most abundant phospholipid in brain-cell membranes, comprising about 30 per cent of the total phospholipid content, while phosphatidylserine (PS) makes up less than 10 per cent. Several studies have been done with PC to investigate its effects on memory. The results have not been consistent. Some have shown positive responses,18,19 while others showed no difference in memory or learning after administration of lecithin, a mix of phospholipids derived from sources such as egg, soy and meats in which PC predominates.20

A number of studies have evaluated the role of bovine cortex PS (BC-PS) in cognitive function, particularly in age-associated memory impairment and Alzheimer's disease. Most of these studies have indicated that BC-PS improves memory and cognition in those with age-related cognitive decline, and helps improve memory and recall in Alzheimer's patients.21,22,23,24 (Because of BSE or mad-cow concerns, most of the PS supply today is no longer derived from bovines.)

Carnitine has been identified as helpful to those with Alzheimer's disease, age-related cognitive decline and depression. It helps form the important brain chemical acetylcholine, a neurotransmitter that is depleted in patients with Alzheimer's, and may also, by improving mitochondrial stability and energy throughput, boost neuronal ergonomics and repair mechanisms.

Animal studies have also found that carnitine can induce the production of nerve-growth factor, a type of protein that helps regenerate neurons.25 Some patients with Alzheimer's are deficient in the enzyme that converts carnitine to acetyl-L-carnitine, and may benefit from carnitine supplements.26 There have been a number of studies on the use of carnitine in treating Alzheimer's, suggesting a slower rate of deterioration for some groups.27,28,29,30 Acetyl-L-carnitine has also been found to improve cognitive function and mood in those suffering from age-related cognitive decline.31,32,33

St John's wort (Hypericum perforatum) has as one of its main active components hyperforin (2-4 per cent), which has been shown to inhibit the re-uptake of serotonin, dopamine and norepinephrine. It has therefore been identified as the most likely antidepressant compound in St John's wort.34,35,36,37,38 Hyperforin has been shown to be a dose-related marker for antidepressant efficacy in humans.39,40,41

Another component of St John's wort believed to have antidepressant effects is the flavonoid amentoflavone.42,43 This could exert its antidepressant action by binding benzodiazepine receptors in the brain. Clinical studies have indicated that St John's wort has antidepressant effects, with successful treatment of patients with mild and moderate depression.44,45,46

In an analysis of 23 randomised trials involving more than 1,700 patients, one review found St John's wort to be significantly superior to a placebo and as effective as standard antidepressants with fewer side effects.47 Although it is successful in treating mild to moderate depression, it is not effective in treating severe depression.48,49,50,51,52,53

Kava (Piper methysticum) contains a variety of chemicals known as kavalactones, which influence a number of the brain receptors involved in relaxation and mental clarity. Its anti-anxiety effects have been noted in a number of human studies. One of the most comprehensive human trials, involving giving a course of kavalactones to more than 100 patients with a range of anxiety disorders, found improvements in tension and mood.54

The German Commission E Monograph on herbal medicines has summarized the effects of kava on anxiety as well as on mental alertness and concentration.55 These include enhanced reaction times in dealing with a range of mental and verbal tasks as well as improvements in mood.

Ginkgo (Ginkgo biloba) contains flavonoids, particularly kaempferol, quercetin and isorhamnetin, and terpene lactones, particularly ginkgolides and bilobides. The active ingredients in ginkgo are believed to produce their beneficial effects by acting as antioxidants, preventing red blood cells and platelets from aggregating to form clots, allowing more oxygen to reach neurons, and by inducing relaxation of the muscles surrounding blood vessels.56 Because it improves communication between nerve cells and enhances blood flow to the brain, it has been used in the treatment of Parkinson's and Alzheimer's, helping to improve cognitive performance.57

Ginseng has several genera: Asian ginseng (Panax ginseng), American ginseng (Panax quinquefolius), and Siberian ginseng (Eleutherococcus chinensis) — now commonly referred to as Eleuthero. Studies of ginseng use in humans have shown both improvements in cognitive function, including its use in combination with ginkgo, as well as reduced anxiety, and greater sense of well being.58,59,60,61

(Excerpted from Performance Functional Foods, David H Watson, editor. ISBN 0-8493-1742-8. Published by Woodhead Publishing Ltd, England.

Paul Clayton, PhD, is chair of the Forum on Food and Health at the Royal Society of Medicine. He is author of Health Defence (Accelerated Learning Systems, 2004) and After Atkins (Robinson Publishing, 2005).
Respond: [email protected]

Carbs: Proof of 'comfort food' concept

There no longer is any doubt that what we eat can influence mood and mental performance. In the context of mood, the intake of carbohydrates and protein has received the most attention — particularly carbohydrates and their effect on brain serotonin synthesis.

Profound effects of an increased intake of carbohydrates on mood have been particularly detected among depressive patients, whereas in nonclinical subjects often no effects, or just slight and contradictory changes in mood, are revealed.1,2,3

The connection between carbohydrate intake and the synthesis of brain serotonin occurs because the production of this neurotransmitter is limited by the availability of its precursor, the dietary amino acid tryptophan. Brain concentrations of this precursor are controlled by the intake of carbohydrates as compared to protein.

Because tryptophan cannot be enzymatically synthesised in mammals, this precursor for the synthesis of serotonin must come from protein sources. However, in a sequence of impressive studies, researchers demonstrated that a balanced or protein-rich diet causes a decline in brain tryptophan and serotonin concentrations. Contrarily, a carbohydrate-rich protein-poor diet caused the opposite effect and was found to increase brain tryptophan and serotonin levels.4,5,6 This apparent anomalous observation is explained because plasma tryptophan competes with the other large neutral amino acids, including valine, tyrosine, isoleucine, leucine and phenylalanine (the LNAAs), for transport across the blood-brain barrier into the brain, because they share the same transport carrier.

In one study, 24 healthy subjects with a high proneness to stress, and 24 healthy control subjects with a low stress proneness participated in an acute-stress experiment using both a carbohydrate-rich, protein-poor diet and a protein-rich, carbohydrate-poor diet.7 Results revealed a significant 42 per cent increase in the plasma tryptophan/LNAA ratio during the carbohydrate-rich, protein-poor diet compared with the protein-rich, carbohydrate-poor diet. During the carbohydrate-rich, protein-poor diet, only stress-prone subjects were prevented from a stress-induced rise in depressive mood and a cortisol stress response. Beneficial effects of this dietary condition on cognitive performance have also been demonstrated exclusively in stress-prone subjects.8

— Rob Markus University of Maastricht The Netherlands

1. Spring B, et al. Carbohydrates, tryptophan, and behaviour: a methodological review. Psychol Bull 1987;102:234-56.
2. Christensen L. The effects of carbohydrates on affect. Nutrition 1997;13:503-14.
3. Bellisle F, et al. Functional food science and behaviour and psychological functions. Br J Nutr 1998;80(1):S173-S193.
4. Fernstrom JD, Wurtman RJ. Brain serotonin content: increase following ingestion of carbohydrate diet. Science 1971;174:1023-5.
5. Fernstrom JD, et al. Correlations between brain tryptophan and plasma neutral amino acids levels following food consumption in rats. Life Sciences 1973;13:517.
6. Curzon G. Effects of food intake on brain transmitter amine precursors and amine synthesis. In: Sandler M and Silverstone T (eds): Psychopharmacology 1991;3:23-8.
7. Markus CR, et al. Does carbohydrate, protein poor food prevent a deterioration of mood and cognitive performance of stress-prone subjects when subjected to a stressful task? Appetite 1998;31:49-65.
8. Markus CR, et al. Carbohydrate intake improves cognitive performance of stress-prone individuals under controllable laboratory stress. Br J Nutr 1999;82:457-67.

Case study: With the right ingredient, functional beverages may take a quantum leap

Functional beverages are soaring: a half-dozen Super Bowl commercials, Vitamin Water doubling its annual sales and then selling to Coca-Cola for $4.1 billion last May, stock in Hansen Natural — maker of Monster energy drink — rising by 1,200 per cent in three years.

And yet, the only innovation of late in functional beverages is to add ever-increasing quantities of caffeine to the mix. Look for an innovation that could create a whole new drink category — call it caffeine without the caffeine. It's based on the amino acid L-theanine, which naturally stimulates specific kinds of brain activity associated with relaxation while decreasing brain waves associated with tension and anxiety. Relaxation without drowsiness. Mental clarity without the jitters.

"It's a category that is missing right now in the US," says Scott Smith, vice president of Taiyo International. "The energy-drinks category is saturated. But there's this other category, not far removed from the concept, that fits. It's what people are trying to achieve with caffeine — not just energy but reduced stress, mental clarity and mental focus."

Taiyo pioneered the market for this unique amino acid found in green tea with its Suntheanine brand. It won the NutrAward for best new product in 2002. It was self-affirmed GRAS in 2005 and just last year Taiyo received FDA notification of no objection to its GRAS application.

"While technically GRAS Self-Affirmation allows for the use of our functional ingredients in the food and beverage category, taking the extra step of notifying the FDA is necessary to get formulated into the larger mainstream products," says Smith. "Since receiving the FDA letter of no objection in 2007, we've been working closely with a number of beverage companies in this new category."

This year's Super Bowl saw the introduction of a number of functional drinks, at least one including Suntheanine, having tag lines of calm, focus and control.

As a bonus to beverage formulators looking to tinker with their caffeinated brands, two studies published in February 2008 found that L-theanine reduced the negative side effects of caffeine — headaches and tiredness after the caffeine crash — and enhanced performance more than caffeine alone.1,2

And despite the inclusion of L-theanine into some major brands in 2007, Smith says 2008 will be an even bigger year. Could it be a category-creator, a la Cargill's CoroWise brand sterols' potent combination with Minute Maid orange juice? Only time will tell.

—Todd Runestad

Four functionals with feeling

There is often a blurry line between 'mood' and outright 'depression.' This fuzziness of terms and understanding might be enough of a roadblock to keep the trendy catchword 'mood food' from growing out of its niche. A clear distinction is the temporal, stress-induced nature of the former, and the deeper tenure of the latter. Savvy marketers who can help develop products and position them outside of the clinical realm and into the wellness category likely stand a greater chance of success. Here are four ingredients that are bona-fide players in the mood-food realm.

GABA: Gamma aminobutyric acid (GABA), an amino acid produced by the brain, produces a relaxation effect by influencing the levels of the neurotransmitters dopamine and serotonin. GABA acts like a brake during times of runaway stress. Indeed, anxiety drugs like benzodiazepines work by stimulating GABA receptors to induce relaxation; low levels can result in anxiety and insomnia.1 GABA production is stimulated by magnesium; GABA activity is increased by L-taurine. In one human study, GABA induced relaxation and reduced anxiety better than L-theanine or placebo; its effects were seen within an hour.2

TeaL-theanine: An amino acid found almost solely in tea plants is also largely responsible for the taste of green tea.3 It has anti-stress effects by blocking glutamate receptors in the brain, reducing psychological and physiological stress responses.4 Other studies suggest theanine releases dopamine in a way that is different from glutamate transporter blockers, though the result is the same: an inhibition of excitatory neurotransmission and relief of stress.5 Theanine has been shown to significantly decrease blood pressure in hypertensive rats.6 A dose of 50-200mg will show effects within 40 minutes.3 Two new studies show that combining L-theanine with caffeine enhances performance in terms of attention switching and the ability to ignore distraction, which would ameliorate the detrimental effects of caffeine overstimulation.7,8 L-theanine is also involved in forming GABA.

Lactium: This milk protein hydrolysate promotes relaxation with no sedative effect. It was found to be the nutrient that makes babies calm after they have nursed. The casein compound has been isolated for its anti-anxiety benefits, and may be used in supplements and beverages. It is the active ingredient in drinks like Dreamerz from Brand New Brands, which also contains melatonin; other similar beverages on the market are using lactium with L-theanine. In animal studies, it improves sleep in rats subjected to chronic mild stress, and was also shown to decrease anxiety in a similar manner but via different mechanism and without the side effects of diazepam (Valium).9,10 Human follow-up trials have demonstrated lactium decreases plasma cortisol concentrations (a measure of stress), maintains heart rate, and lowers blood pressure in patients put in stressful situations.11

Choline: This B vitamin is a component of the neurotransmitter acetylcholine, as well as a part of phosphatidylcholine, a phospholipid needed by brain cells. Because it is involved in memory, motivation and thinking, deficient levels have been found to correlate with poor memory and concentration. Harvard researchers found antidepressantlike effects of CDP-choline. These effects, found in rats, were heightened when combined with omega-3 fatty acids, to the point where less of each nutrient was required when taken together — a point that should not be lost on product developers. Also of note, there was no effect seen at three or 10 days, but there was by 30 days of treatment.12

—Todd Runestad

1. No authors listed. Gamma-Aminobutyric Acid (GABA) ? Monograph. Altern Med Rev 2007 Sep;12(3):274-9.
2. Abdou AM, et al. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors 2006;26(3):201-8.
3. Juneja LR, et al. L-theanine ? a unique amino acid of green tea and its relaxation effects in humans. Trends Food Sci Tech 1999 Jun;10(6-7):199-204.
4. Kimura K, et al. L-Theanine reduces psychological and physiological stress resonses. Biol Phychol 2007 Jan;74(1):39-45.
5. Yamada T,e t al. Effects of theanine, r-glutamylethylamide, on neurotanmitter release and its relationship with glutamic acid neutotransmission. Nutr Neurosci 2005 Aug;8(4):219-26.
6. Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-glutamylmethylamide in spontaneously hypertensive rats. Life Sci 1998;62(12):1065-8.
7. Bryan J. Psychological effects of dietary components of tea: caffine and L-theanine. Nutr Rev 2008 Feb;66(2):82-90.
8. Haskell CF, et al. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol Psychol 2008 Feb;77(2):113-22.]
9. Guesdon B, et al. A tryptic hydrolysate from bovine milk alphaS1-casein improves sleep in rats subjected to chronic mild stress. Peptides 2006 Jun;27(6):1476-82.
10. Violle N, et al. Ethological comparison of the effects of a bovine alpha s1-casein tryptic hydrolysate and diazepam on the behaviour of rats in two models of anxiety. Pharmacol Biochem Behav 2006 Jul;84(3):517-23.
11. Messaoudi M, et al. Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations. Eur J Nutr 2005 Mar;44(2):128-32.
12. Carlezon WA, et al. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry 2005 Feb 15;57(4):343-50.


What's eating you?: The next superfruit application

Fi speaks with Arjan Scheepens, PhD, neuroscientist at HortResearch in New Zealand. He is measuring specific psycho- and bio-active effects of plant-based materials with a view to designing natural nutraceuticals to relieve stress, hypertension and age-related cognitive decline. For the complete conversation, click here.

Fi: What is it in New Zealand fruits that make it 'mood-food'?

LB: A combination of things. Our focus is on designing intelligent synergies between compounds that aid in absorption, and increasing bioavailability and access through the blood/brain barrier. Several targets outside the brain can be targeted more easily with ingested functional foods to alleviate some symptoms of stress and anxiety, such as beta-blockers or ACE inhibitors, classically used to treat hypertension.

Fi: What is the mechanism of action?

LB: It depends on the target. For anxiety we are interested in phytochemicals that increase GABA function or which are directly GABAergic, as well as monoamine oxidase inhibitors. Also, we look at synergies to protect bioactive phytochemicals from metabolic degradation, or enhance their absorption. Some of our more edgy science is in search of plant-derived CRH-R1 antagonists — a hot topic in current clinical pharmacology.

Fi: Are you looking into specific applications?

LB: We want the fruits of our research to end up in a consumer product. Our current clinical trial is with a product that may decrease negative effects of stress and increase cerebral blood flow and thus possibly improve cognition, especially whilst under stress — an enormous problem in today's workplace.

Select suppliers: nutrients to entertain the brain

BI Nutraceuticals
Full line of Identilok botanical powders, identified and confir
med via thin-layer chromatography, microscopic image analysis, organoleptic testing and other quality standards.

Chemi Nutra
AlphaSize alpha-GPC is a choline source; SerinAid PhosphatidylSerine; OmegaAid PS is an omega-3/PS combination.

SharpGPC is alpha-GPC, which adds to the company's cognitive line including PS-DHA conjugate SharpPS gold, and straight-up PS ingredient SharpPS.

Uniquely positioned EPA and DHA portfolio into a range of condition-specific formulations based on specific concentrations of the omega-3s. Its Mood & Mind Health has high amounts of EPA.

Neuravena EFLA 955 is a wild green-oat extract that targets stressed-out adults, helping with tiredness, stress and anxiety.

GAT Food Essentials
Denomega GAT 100 omega-3 EPA/DHA and Pro Corde ALA alpha-linolenic acid are part of its polyunsaturated fatty acid profile.

Home to the world's largest fruit-gene and compound database, New Zealand company researches novel breeding and unique combinations of fruits for beneficial health effects, including a fruit-juice cocktail that appears to reduce stress and improve memory. Licensing is planned.

Lactium brand casein hydrolysate helps regulate stress symptoms, supplied by French dairy developer and marketer of dairy-derived speciality ingredients.

Kyowa Hakko
Cognizin brand citicoline changes brain chemistry and activity in certain areas of the brain, enhancing attention, memory, mood, focus and concentration.

Probio-Stick containing Lactobacillus acidophilus Rosell-52 and Bifidobacterium longum Rosell-175 relieves stress-induced gastrointestinal problems.

French company manufactures and sells plant extracts for the food, flavour and nutraceuticals industries.

Next Pharmaceuticals
Relora is a proprietary blend of Magnolia officinalis and Phellodendron amurense used in stress management and stress-related appetite control, without causing drowsiness.

Nutraceuticals International
Bulk supplier of concentrated botanical extracts, amino acids and specialities.

Sigma-tau HealthScience
AminoCarnitines deliver L-carnitine along with a specific amino acid in one distinct molecule, like ArginoCarn and GlycoCarn.

Suntheanine brand L-theanine was the pioneer in supplying this amino acid, which promotes relaxation without drowsiness.

"It" ingredient: fish oil

FI talked with Baldur Hjaltason, EPAX sales manager for North America, Japan and China, on the latest application for omega-3 fish oils.

FI: EPAX has uniquely positioned itself by offering condition-specific formulas with fish oils, all predicated on different concentrations of EPA and DHA. What is its "Mood & Mind Health" concentration, and how does it differ from other condition-specific formulas?

BH: Our "Mood & Mind Health" product EPAX 6015TG contains a high amount of EPA or minimum 530mg/g. This is the highest EPA product that EPAX offers. Many people suffer from mood swings ranging from depression to violent behaviour and are looking for nutritional support to help them stay emotionally balanced. The effectiveness of omega-3 fatty acids in the treatment of depression comes from several double-blind, placebo-controlled trials conducted by independent groups in different countries. The majority of those trials in adults with unipolar depression have been using eicosapentaenoic acid (EPA) and have consistently reported significant improvements in their symptoms. We have also studies showing that high EPA intake helps achieve remission in bipolar disorder.

EPAX has been working with several leading individuals in this area including Dr Malcolm Garland, who has demonstrated in a paper published in 2005 that "healthy" people function better, feel less fatigued and have reduced levels of anger, anxiety, confusion and depression when taking omega-3 supplements. EPAX products were also used in trials of Dr Garland on effects of omega-3 fatty acids in patients with self-harm.

FI: How does "Mood & Mind Health" differ from "Cognitive Health" — both from a marketing perspective as well as from a formulation perspective?

BH: While science shows that a lack of EPA causes symptoms such as depression and violent behaviour, the fat in the brain is basically made out of DHA. We know how important it is for the mother, both during and after pregnancy, to consume DHA in order to supply the fatty acids to the fetus and then the newborn child through breastfeeding, but less attention has been paid to what the needs are for maintaining the high DHA content in the brain throughout life. Recent studies clearly show that DHA is needed all your life. Therefore, we are promoting our EPAX 1050TG, which contains a minimum of 430mg/g DHA for cognitive health.

EPAX supported a major study on the effects of high DHA in an elderly population of Alzheimer's patients. This study took one year with 174 patients who took EPAX 1050TG daily. The trials determine the effects of DHA on supplementation in cognitive function on patients with mild and moderate Alzheimer's. The results were clear: DHA slowed the onset of mild Alzheimer dementia and improved quality of life.

The Office of Dietary Supplements (ODS) at the National Institute of Health (NIH) publishes an annually bibliography of significant advances in dietary supplement research, highlighting 25 of the most significant dietary supplement research advances of the past year. In 2006, EPAX got the award for this study as one of two on cognitive health.

FI: The science behind fish oils is probably strongest in the cardiovascular health arena. Where does "Mood & Mind Health" stack up, and what are its future prospects?

BH: All surveys have shown that the highest awareness of the omega-3 health benefits is in the cardiovascular health area, so more education is needed to show the benefits of in the mood and mind health area. There are several products on the market targeting this area and doing well, especially for bipolar disorder. Those consumers have experienced the improvement when taking their high-EPA products and that they return to their old symptoms if they stop the treatment.

Older people suffer more from mood and mind health problems. Although many of those people are being treated today with drugs, the authorities are getting more and more aware of the links between diet and behaviour and the influence of nutrition on mental health. Therefore we should expect this category to expand rapidly in the coming years.

FI: Why should manufacturers look at fish oils for their mood/stress finished goods product launches vs other non-fish-oil ingredients?

BH: Although fish oils are very effective in treating self-harm and the onset of Alzheimer's, there is no question that there are many other effective non-fish-oil ingredients that will also help those people. The challenge will be to blend those ingredients together to get the benefits from all of them. However, it is still the omega-3 fatty acids from fish that have the best clinical documentation today.

One of the reasons we are seeing such high rates of mood and mind problems as well as Alzheimer's is due to how much we have changed our diets. We used to eat much more omega-3 fatty acids compared to omega-6 fatty acids. The normal ratio should be around 1:4 but is now up to 1:15. This leads the prostaglandin system in the body to produce many inflammatory compounds that give various clinical symptoms. One of the best known effects of EPA is its anti-inflammatory effects.

FI: What is the difference between the triglyceride (TG) and ethyl ester (EE) forms of fish oils?

BH: In order to concentrate EPA and DHA, the fatty acids must be split from the glycerol backbone molecule. As free fatty acids, their boiling points are too similar, making it difficult to concentrate by high vacuum molecular distillation. Therefore, they are turned into ethyl esters, which widens the boiling point difference, making it easier to separate.

Previously, it was not easy to turn the ethyl ester back to a glycerol backbone molecule. This was done chemically, which resulted in products with a lot of impurities. EPAX is now using state-of-the-art technology with lipases to turn back EPA and DHA as well as the other fatty acids to the glycerol molecule, turning them to the same natural form as in the start.

Fish oil concentrates have been sold as both EE and TG. Some countries do not allow EE product to be sold except as pharmaceuticals, partly because the EE form of EPA and DHA is not found in nature. Most studies have shown that there is equal bioavailablity of EE and TG form of EPA and DHA.

FI: Can you site one or two studies that demonstrate support of mood health?

BH: One of the best overviews is an article written by leading scientists in this area including Marlene Freeman, MD, Joseph Hibbeln, MD and Andrew Stoll, MD, titled, "Omega-3 fatty acids: Evidence basis for treatment and future research in psychiatry" and published in J Clin Psychiatry 67:12 December 2006.

Other major articles include:

  • Nemets, et al. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. American Journal of Psychiatry 2006;163:1098-1100.
  • Peet M & Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Archives of General Psychiatry 2002;43:315-319.
  • Su KP, et al. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 2003;13:267-71.
  • Stoll AL, et al. Omega-3 fatty acids in bipolar disorder: a preliminary, double-blind, placebo-controlled trial. Arch Gen Psych 1999;56(5):407-12.
  • Fontani G, et al. Cognitive and physiological effects of omega-3 polyunsaturated fatty acid supplementation in healthy subjects. Eur J Clin Invest 2005;35:691-9.
  • Garland MR, el al. 2007 op cit.
  • Hallahan B, et al. Omega-3 fatty acid supplementation in patients with recurrent self-harm. Br J Psych 2007;190:118-22.

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