"Of particular interest are the recent findings of Drs. Ronald Fernstorm, Richard Wurtman and others at the Massachusetts Institute of Technology (M.I.T.).  They have proved that the level of serotonin in your brain is directly influenced by the amount of L-tryptophan in your diet" (Feeling Good by David Burns MD).

Dear William,

Many thanks for your rapid response. Dietary tryptophan is an interesting topic because brain levels of serotonin depend on its precursor tryptophan, therefore on the availability of foods rich in tryptophan such as nuts, cereals or bananas. Indeed, Hulsken and colleagues have recently published a review titled ´Food-derived serotonergic modulators: effects on mood and cognition´.

http://www.ncbi.nlm.nih.gov/pubmed/24134856

The authors found ´an inverted U-shaped curve for plasma tryptophan levels, with low and too high tryptophan levels impairing cognition, and moderate to high tryptophan levels improving cognition. This relationship is found for both healthy and vulnerable subjects. Whereas this relationship may also exist for mood, the inverted U-shaped curve for plasma tryptophan levels and mood may be based on different tryptophan concentrations in healthy v. vulnerable individuals´.

This introduces another interesting topic - what about baseline concentrations (deficient or not) of certain nutrients in subjects with mood disorders?

Sleep disorders affect the mood and mental and physical performance. Various factors, including the type of food and time of food intake can affect on sleep. Healthy eating means respecting diversity,balance and moderation in eating the food pyramid and determine the needs of each individual, depending on age and sex, physiological and pathological conditions. Food with high glycemic index and tryptophan reduces the time it takes to fall asleep. That can affect the quality of sleep and performance. Foods such as milk two hours before going to sleep at night, and vegetables because of magnesium and other nutrients are useful.

Most of the research is epidemiological and mechanisms are only proposed. With that said, there is a review article summarizing the relationship of specific nutrients associated with relieving depression, stabilizing bi-polar disorder and schizophrenia. Many of these supplements are found in foods that have declined in consumption in developing countries such as fish and nuts. Major amino acids and omega-3 fatty acids are missing in the modern diet of processed foods.

Below is the link to the review by Lakhand and Vieira, 2008:

http://www.nutritionj.com/content/pdf/1475-2891-7-2.pdf

http://www.nutritionj.com/content/7/1/2

For autism the following article may be helpful:

Nutritional Interventions and Therapies in Autism

A Spectrum of What We Know: Part 2

Maureen E. Geraghty, PhD, RD, LD

doi: 10.1177/1941406410366848 ICAN: Infant, Child, & Adolescent Nutrition April 2010 vol. 2 no. 2 120-133

Aside from supplements such as omega 3, vitamin B6—maganesium, melatonin, methylator pathway nutrients, special diets that restrict casein and gluten and propose special carbohydrates are discussed as they apply to autism in light of evidence from intervention studies.

Dear All,

I endorse your share opinion. I think it is the biorhythm cycle that affect the melatonin, serotonin and  tryptophan which affect mood. Time of sleep and sufficient hours of sleep are important for making a stable mood. Sugar intake at night may affect serotonin secretion and increase your appetites with mood fluctuation state. exercise and a proper diet influence the likelihood balanced lifestyle in a daily basis.   

Research does not always match clinical applications. In fact, clinical management involves using evidenced-based guidelines. The major management of mood disorders are by drugs and avoidance of certain dietary triggers. Prescription sfor healthy options that might help in the management of mood are lacking.

Dear Mariam and Hashem,

Thanks for your input related with the sleep, food and mood interface. In my clinical practice, many patients with mood disorders have comorbid sleep and eating problems / disorders. For many of them, nutirional habits are rather poor and this certainly worsens outcomes. Do you think that professional advice or intervention by a nutritionist is mandatory here? Which clinical symptoms or behaviours should prompt psychiatrists / depressed patients to make an appointment with a nutritionist?

Dear Joan,

Thanks also for your comments. I agree with most, if not all,of them. It is amazing that we are still discovering the mechanisms subserving the clinical benefits of certain nutrients / foods / dietary patterns.

Although "recommendations for healthy options that might help in the management of mood are lacking" in most clinical practice guidelines of mood disorders, which would be your specific suggestions for patients?

There are also a number of nutritional imbalances that can make you prone to depression such as:

Essential fats, do you need more Omega 3?

Homocysteine, is it too high, corrected with B vitamins?

Serotonin levels, do they need boosting with amino acids

Blood sugar balance

Levels of the nutrients chromium and Vitamin D

Food intolerances, could they be making you sad?

 Dear  Vicent

Nutrition plays an important role in the treatment of various diseases and Clinical dietitian will help you in treating patients,

ex: Vegetables containing folic acid, and magnesium are effective in reducing stress and anxiety.And foods that increase the body's secretion of morphine and serotonin as well as Calorie intake and meal are important.With the help of a nutritionist and the balance variability in eating according to the food pyramid is recommended for treatment of patients

Vicent, thank you for asking my recommendations. Perhaps testing for allergies could be a first step. One diet does not fit all. First and foremost are the patient's food preferences. I believe in a client-centered approach whereby working with the patient you could determine suitable dietary modifications (from their existing dietary practices). Sometimes it is the food patterns (time of day, amount per meal) that need to be modified. I suggest a registered dietitian (RD) be involved with the team of medical professionals in developing an optimal treatment plan.

There are a number of comments in this discussion that need clarifying or correcting, and an important issue that has not been raised.

1. The statement that Fernstrom and Wurtman “have proved that the level of serotonin in your brain is directly influenced by the amount of L-tryptophan in your diet” is not quite true. They demonstrated that tryptophan administration can increase brain serotonin synthesis in rat brain and many others have also demonstrated that this is true for human brain. However, they also demonstrated that tryptophan is transported into brain by a transporter that is active towards all large neutral amino acids, i.e. not only tryptophan but also phenylalanine, tyrosine, leucine, isoleucine and valine. There is competition between the various amino acids for the transporter and as a result brain tryptophan can, as a rough approximation, be predicted by the ratio of plasma tryptophan to the sum of the plasma concentration of the other large neutral amino acids (trp/LNAA). Tryptophan happens to be the least abundant amino acid in most proteins, so when tryptophan (i.e. protein) is ingested as a part of a normal diet plasma tryptophan will increase but the LNAA will increase even more. As a result trp/LNAA, brain tryptophan and brain serotonin will decrease. The effect in humans is so small as not be significant. This is all discussed in detail in the paper you will find here: https://www.researchgate.net/publication/258215311_L-Tryptophan_Biochemical_nutritional_and_pharmacological_aspects

2. You have to distinguish between nutrition and the use of components of the diet in purified form at high doses. For example, tryptophan when given at doses of 3g per day or more has an antidepressant effect (see Cochrane review at http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003198/abstract) presumably because of the increase in brain serotonin synthesis. However, as discussed above, the 0.7 to 1.0 g per day of tryptophan that most people ingest as part of a normal diet will not raise brain tryptophan or serotonin and is certainly not an antidepressant. To me, tryptophan in purified form is a drug, and regulatory agencies in the Canada and the UK approved it as a prescription drug for the treatment of depression (although I believe it is now available over the counter in the UK). In the USA it is available over the counter as a dietary supplement. Another dietary constituent discussed by Lakh and and Vieira (see comment by Joan for the link) is S-adenosylmethionine (SAM). It is an antidepressant at a dose of 1g per day or more which is orders of magnitude large than the amount ingested in the diet. Again to me that is a drug. The article by Hulksen et al (see comment by Vincent for the link) discusses the effects of alpha-lactalbumin, which is a minor constituent of milk that contains unusually high levels of tryptophan does in fact raise brain tryptophan a bit (although not as much as tryptophan because it does contain LNAA). You might want to call that a dietary supplement, but I cannot see why anyone would use it. A search of websites selling alpha-lactalbumin and tryptophan suggests that tryptophan in purified form is cheaper than the tryptophan in alpha-lactalbumin.

3. The Hulksen article does not talk about real diet. It discusses work with alpha-lactalbumin and the acute tryptophan depletion technique (see https://www.researchgate.net/publication/235688848_Acute_tryptophan_depletion_in_humans_a_review_of_theoretical_practical_and_ethical_aspects) neither of which have anything to do with real diets. Their conclusion about the U-shaped curve for plasma tryptophan levels and mood is based on non-nutritional studies of that type and is not even supported particularly well by the data they present.

4. Maryam says that “Food with high glycemic index and tryptophan reduces the time it takes to fall asleep.” It is important to clarify that tryptophan refers to purified tryptophan, not tryptophan in food. In relation to the comment that milk two hours before going to sleep is useful, I know that this is folklore but I am not aware of any controlled trials demonstrating this. Can anyone enlighten me?

5. There are now many studies suggesting that those with poor diets are more likely to become depressed than those with good diets (e.g. the Mediterranean diet, the New Nordic diet). Of course this type of epidemiological study does not imply anything about cause and effect. It is likely that those with depressed mood that later becomes clinical depression might select worse diets than those with good mood. Furthermore, not all the studies controlled for possible confounding variables such as exercise, given that those with good diet are more likely to exercise and that may be a protective factor against depression.

6. A recent meta-analysis concluded that omega-3 polyunsaturated fatty acid supplements are effective in the treatment of depression. http://dx.doi.org/10.1371%2Fjournal.pone.0096905 

7. An old literature suggests that the incidence of folate deficiency is higher in depressed patients than in the general population. This is not surprising as depression is associated with anorexia. However, in rats and possibly in human folate deficiency causes a decrease in serotonin synthesis. A number of studies suggest that folate or methyl-folate enhance the recovery of depressed patients being treated with depression. While folate is probably not often a cause of depression folate deficiency that occurs due to depression and inadequate diet may help prevent recovery. This is discussed here https://www.researchgate.net/publication/6453069_Folate_and_depression--a_neglected_problem, and a recent high quality study showing that methyl-folate can help recovery from depression is here http://ajp.psychiatryonline.org/article.aspx?articleID=1461102#Abstract.

8. The question was “Are nutritional interventions part of daily clinical management of people with mood disorders?” Good diet might help, but there is no evidence that it will help cure depression. Tryptophan, SAM, omega-3 polyunsaturated fatty acids and folate or methyl-folate are all dietary components that may be helpful in the treatment of some depressed patients.

Article L-Tryptophan: Biochemical, nutritional and pharmacological aspects

Article Acute tryptophan depletion in humans: A review of theoretica...

Article Folate and depression - A neglected problem

Simone, thank you for your detailed response. You are correct that the discussion regressed to clinical suggestions. Exercise is another factor that may have an association with better mood in depressed patients. The American Psychological Association suggests that exercise be incorporated in the treatment of persons with depression: http://www.apa.org/monitor/2011/12/exercise.aspx. Since the biochemical mechanisms of particular nutrients and brain chemistry have not been clearly provided, epidemiological evidence should be considered in clinical practice as well as research associations that are valid. It is important to differentiate between real foods and concentrated forms of food molecules (such as tryptophan). Individual treatment should be considered in the case of missing evidence.

I would like to make another point about the Hulsken article The abstract includes the following sentence “Because serotonin levels in the brain are dependent on the availability of the food-derived precursor tryptophan, foods such as chicken, soyabeans, cereals, tuna, nuts and bananas may serve as an alternative to improve mood and cognition”. The idea that bananas, a low protein food, might contain high levels of tryptophan is peculiar. In fact, the US Department of Agriculture Nutrient Database (a very useful free source of information at http://ndb.nal.usda.gov/ndb/) gives the protein content of bananas as 1.09% and the tryptophan content as 0.009%. For a high protein source such as eggs the relevant figures are 12.56% for protein, and 0.167% for tryptophan. Bananas contain serotonin and there is a myth, perpetuated by the web, that eating bananas decreases depression by increasing brain serotonin. (The kewords “bananas” and “serotonin” produce 419,000 hits on Google.) Of course, even if the serotonin in foods was not metabolized rapidly by monoamine oxidase it would not cross the blood-brain barrier. (And why bananas was chosen for this myth is not clear to me, as they contain only 15µg/g of serotonin, compared to values an order of magnitude higher for various nuts http://www.ncbi.nlm.nih.gov/pubmed/2413754). At some point the myth that bananas can cure depression because of their serotonin content seems to have changed into the myth that bananas contain high levels of tryptophan. (The kewords “bananas” and “tryptophan” produce 194,000 hits on Google.)

There are many myths about nutrition and the brain, mood and behavior. I find it distressing that a respectable journal such as Nutrition Research Reviews (published by Cambridge University Press; impact factor 3.86) should help perpetuate one of these myths. There was obviously a big problem with the peer review of the Hulsken paper. I am uncertain about how to help destroy myths about nutrition and the brain. I have been teaching about these issues to students for nearly 4 decades and taking any opportunity to talk to the popular press about them. I will, as soon as I have time, post a comment about the article on PubMed. Does anyone have other ideas about how to combat the myths?

I think that nutrition and a specially diet may playing an important role in the treatment of patients with mood disorders like depression.

Therefore I assumed that the clinical practice imply a balanced diet and well  adjusted nutritions for these patients.

In my opinion the diet has to be ajusted for every patient individually in according to the kind and the medical reason of the mood disorder.

It is a different if the depression is triggered by toxins from an infection, drugs, an organic disfunction or a psychologically event. But I do not know whether such a differentiation is possible in a clinical routine.

I agree with Simons defence that the treatment with specially products are drug like and have no relation to the preparation of food.

But a good cook or a nutrition expert knows how to satisfy people. It may be simple to choose the right food composition to assist a patient with mood disorder in a preferred way.

An example is the choise of the kind of meat and of vegetables and especially of the added spices. Also the choise of the kind of carbohydrates is important. Vegetables with normal starch are metabolized in the stomach into sugars.

If you have vegetables with parts of resistant starch you found a metabolisation in the small intestine into fatty acids, too. The second  type of starch often clears the mind by interaction with the bilious system. In this way bread fruit, water chestnut, topinambur, longane, rambutane or chickpeas are important food ingredients. Also the meat of goat, hare or shrimps and some scallops clears the mood especially

cooked with the spices of nutmeg, atractylodis, astragalus, ginger or fennel in a coconut milk. Also rice prepared with rosted sesam and soft spices like a drop of cananga odorata, galanga or chrysamthemum has a positive effect of the mood.

The effect of a balanced nutrition as moodlifter is well known. But I do not know whether this effect will be considered in the clinical use or in the practical advices for the patients.

I am pleased to get some literature reffering to this problem.

Very nice to see all the conversation. Especially by Simon N Young. There is no doubt that neurotransmittors such as dopamine and serotonin have an impact on mood benefit. However majority of evidence have arrived from depletion studies, where subjects with reduced neurotransmittors are depressed or towards that state. I would comment on modulating serotonin with nutritional interventions with foods such has banana. If we understand the mechanism on how diet influences mood. Dietary ingredients  which stimulates enterochromaffin cells in the intestine would only show desired benefit. Enterochromafin cells release serotonin at distal end (not the gut lumen), where it stimulates vagus nerve to elicit mood benefit. So diet rich in serotonin analogues would have very less or no benefit on mood benefit. But diet which can stimulate serotnin release would ideally influence mood.

Does this make a logic?

I find many people who have been diagnosed with depression are anxious, and respond well to oral magnesium glycinate and inositol. Depression may be due to low energy, in which case magnesium, B vitamins and ubiquinol may be useful. Depression may be a result of high blood histamine, in which case Epsom salt baths, magnesium glycinate and copper (if deficient) may reduce histamine, by sulphation, methylation and histaminase. Vitamin D may help, and low vitamin D may cause winter depression. Depressed people may refuse to go out even in summer, making themselves more depressed. Exercise helps, as does company. Individuals may respond to specific foods with elation, followed by depression. Alcohol can cause depression. Vanadium appears to be associated with mania, and is removed by high dose vitamin C.