Food and Mood

Question 1

What is depression?

Answer 1

not 1 full definition but….

Depression is a low mood that lasts for a long time, and affects your everyday life.” (MIND, 2019)

“Depression is a mood disorder characterised by hopelessness, sadness and misery” (Thomas, 2002).

“Depression is a broad and heterogeneous diagnosis. Central to it is depressed mood and/or loss of pleasure in most activities” (NICE, 2009)

Question 2

Depression Statistics (WHO, 2021)

Answer 2

Estimated 3.8% of the global population affected, including 5.0% among adults and 5.7% among adults older than 60 years

Approximately 280 million people in the world have depression

Over 700 000 people die due to suicide every year. Suicide is the fourth leading cause of death in 15-29-year-olds

Question 3

What are the symptoms of depression?

Answer 3

Unable to cope
Feeling down, upset or tearful
Finding little pleasure in life
Suicidal thoughts
Feeling isolated
Low self-confidence or self-esteem
Numbness
Lethargy and tiredness
Loss of interest in activities
Restless, agitated or irritable
Sadness or feeling unhappy
Sleeping problems
Loss of appetite

Question 4

Formal Diagnosis of depressive disorders?

Answer 4

ICD-10
classification system requires at least four out of ten criteria listed in the manual

DSM-V
system requires at least five out of nine criteria to be met for a diagnosis of major depressive disorder (depression).

Question 5

Risk factors for depression

Answer 5

stress from work/school
relationship problems
family history
money problems
loss of social support
loss of parent before the age of 10

Question 6

Contributors to onset of depression (Volker & Ng, 2006; Lopresti et al., 2013)

Psychological, Genetic, Social/environmental

Answer 6

Psychological Factors:
A persons style of thought and the way in which they interpret and react to life experiences may either protect or predispose them to mood disorders.
Make negative statements about themselves and their abilities
Personality traits
Distorted views of reality
Unrealistic goals

Genetic Factors:
Familial aggregation: Depressive disorders more common in the relatives of depressed subjects than in the population at large

Concordance rateofmajor depressive disorderfor MZtwinswas 46% and for non-identical (DZ)twinswas 20% (McGuffin et al., 1996).

This shows that there isa heritability factor formajor depression

Social/environmental Factors:
Clinical depression is usually preceded by a greater frequency of demanding life events
Acute adverse changes in environmental and social circumstances appear to have an effect on the onset, maintenance and relapse of depression.

Question 7

Biological factors: dysregulated pathways in depression (Lopresti et al., 2013).

Answer 7

An increased size and activity of the pituitary and adrenal glands are found in major depression (Nemeroff et al., 1992).

• Decreased antioxidant status and elevated oxidative and nitrosative stress are found in patients with major depression (Maes et al., 2011).

Elevated levels of C-reactive protein (CRP), interleukin-1 (IL-1), and interleukin-6 (IL-6) are reported in depression (Howren et al., 2009)

• BDNF levels are low in people with major depression (Duman, 2009; Lee and Kim, 2010)

Depression is also associated with an increased availability of monoamine oxidase, an enzyme that metabolises serotonin in the brain (Meyer et al., 2006)

Question 8

Protein and mood

Answer 8

tryptophan -> 5-HTP -> Serotonin

Serotonin (5-hydroxytryptamine; 5-HT) is synthesized from tryptophan.

Supplementation with this amino acid, or its metabolite, 5-HTP, is hypothesized to normalise serotonin synthesis and its function as an antidepressant within the brain (Parker & Brotchie, 2011).

Question 9

Tryptophan – Research Evidence?

Answer 9

Both trials showed superiority of supplementation to placebo in alleviating depression, although side effects reported by some subjects.

Van Praag et al., (1972) tested 5-HTP in 10 severely depressed patients. The intervention involved 3 weeks of 5-HTP given as 200mg capsules at a dosage increasing to 3000mg daily and to a total of 50g for 3 weeks, followed by 2 weeks of placebo. Control group were given a placebo for duration of 5 week trial.

Thompson et al., (1982) tested tryptophan and involved 28 patients with mild depression and 26 controls. The patients with depression were given the placebo for 1 week followed by 12 weeks of tryptophan (3g/d), with 26 controls given placebo for 13 weeks.

Question 10

Tryptophan supplementation: Systematic review (Kikuchi et al., 2020)

Answer 10

Systematic review that includes 11 RCTs that examined the effects of TRP intake on positive and negative mood in healthy adult populations:
Concluded that taking 0.14–3 g of TRP per day in addition to usual dietary intake can be expected to improve the mood of healthy individuals.

Question 11

Carbohydrate and mood

Answer 11

facilitates the amino acid tryptophan into the brain to be converted into seritonin

Question 12

Source of seretonin

Answer 12

banana

walnuts

Question 13

Carbohydrate and mood – Research evidence?

Answer 13

Fernstrom (1981) showed that ingestion of a single carbohydrate-rich meal by rats raised brain tryptophan and 5-HT.
One week on a high fat/low-carb diet decreased serotonin release in the hypothalamus (Banas et al., 2009).

Various authors (Teff et al., 1989; Spring et al., 1987; Rogers, 1995; Soh & Walter, 2011) suggest that it is very difficult to alter blood tryptophan levels through dietary methods alone outside of a laboratory research setting.

Question 14

Glycemic index/glycemic load and mood: Meta-analysis (Solari-Moghaddam et al., 2019)

Answer 14

This meta-analysis showed no significant association between either dietary GI or GL and odds of depression in cross-sectional studies.

They did find a significant positive association between dietary GI and risk of depression in cohort studies

They also found a significant change in depression score after consumption of a high-GL diet in clinical trials

Question 15

Introduction to fatty acids - Structure

Answer 15

• A chain of carbon atoms with the required number of hydrogen atoms attached (Hydrocarbon chains)
• A carboxylic acid residue at one end of the chain
• A methyl group at the other end of the chain.

Can se saturated or unsaturated with hydrogen

Question 16

Human desaturases

Answer 16

Human desaturase enzymes can only operate on the bonds between the first 9 carbons starting after the carboxyl group.

Food is the only supply of fatty acids with one or more double bonds in the out of range part of the molecule.

Therefore, fatty acids with one or more double bonds in the out of range part of the molecule are termed Essential Fatty Acids (EFAs).

Question 17

Essential Fatty Acids

Answer 17

Linoleic acid – omega-6

Alpha linoleic acid - omega-3

Metabolism allows biosynthesis of other fatty acids

Question 18

Factors influencing the efficiency of conversion of EFAs to LC-PUFAs

Answer 18

Conversion of LA to AA is typically very efficient
Conversion of ALA to EPA and DHA is much less efficient
For this reason omega-3 LC-PUFAs are sometimes referred to as ‘conditionally essential’

Dietary factors:
Competition for enzymes involved in fatty acid elongation and desaturation between n-3 and n-6 fatty acids.

Synthesis of longer chain n-3 fatty acids from LA within the body is competitively slowed by n-6 analogues.

High dietary intake of n-6 PUFAs can reduce n-3 fatty acid conversion by as much as 40%

Question 19

Effect of type of fatty acid tail on membrane fluidity:

Answer 19

Incorporation of omega-3 fatty acids into neuronal cell membranes required in order for proper functioning of the membranes and ultimately neuronal functioning.

Suggested that Omega 3 has more anti-inflammitory effects compared to O6 (more fluid)

Question 20

Omega-3 fatty acids: Observational evidence

Answer 20

Epidemiological data suggests lower prevalence of mood disorders with higher fish consumption (kamphuis et al., 2006; Appleton et al., 2007).

Some research suggests an association between low omega-3 status and depressive symptoms (Edwards et al., 1998; Mcnamara et al., 2007; Astorg et al., 2008; Feart et al., 2008; Lin & Su, 2010).

Question 21

Omega-3 fatty acids - Intervention studies (Lin and Su, 2007)

Answer 21

Lin and Su (2007) analysed studies by different EPA dosages and suggested that doses >4000mg/d had significantly greater antidepressant effects than placebo.

> 2000mg/d had no effect.

Therefore, we may only see an effect in studies that have given larger doses and at doses way higher than is achievable through dietary means alone.

Question 22

Limitations of this research on Omega 3 fatty acid?

Answer 22

Problems with this research to date:
These trials tended to be small (n=20-77)

Short duration

Use differing doses of omega-3 fatty acids - What is the optimum dose? Are they using enough to have an effect?

Different ratios of EPA/DHA – what ratio should we use?

Heterogeneous populations under study – makes it very difficult to compare findings

Different severity of depression

Different age categories
Etc…

And the does of omega-3 LCPUFA (up to 9.6g/d) associated with the largest effects in adults is very much higher than could be realistically achieved through diet alone.

Different measures/assessments of mood and depression used

Very difficult to measure/quantify

Question 23

Potential mechanism of action?

Answer 23

Folate (B9) is a water soluble B vitamin:
Dihydrofolate – natural form
Leafy green vegetables, broccoli, asparagus, peas, legumes, chickpeas, brown rice, fortified breakfast cereals, etc..

Folic acid (synthetic form)

Neither of these forms is biologically active and must be converted to L-methylfolate

Question 24

L-methylfolate and synthesis of neurotransmitters

Answer 24

folate
dihydrofolate
tetrahydrofolate
5,10 methylene THF
L-methylfolate

L-methylfolate = modulates transmitter to modulate the production of BH4

BH4 activates synthesis of translaters to make =
dopamine -> norepinephrine
serotonin

Question 25

Folate and mood: Folate intake

Answer 25

Only 23.6% of men consumed the recommended 300ug/d of folate.

Although, higher total intakes of both vitamin B6 and B12 were associated with a decreased likelihood of the development of depressive symptoms over an average of 7.2y.

Question 26

Folate and mood: folate status

Answer 26

Patients without deficiency but with folate levels near the low end of the normal range also reported low mood.

In contrast, Pennix et al. (2000), did not find a significant effect of plasma folate levels on depression in women.

Take peoples blood samples – lots of obs but mixed bag of findings

Question 27

Folate and mood: Supplementary folic acid

Answer 27

A Cochrane review (Taylor et al., 2004) of three small trials involving 247 patients suggests some benefit in using folic acid supplements alone or in combination with antidepressants.
The greatest effect was seen in those with the highest increase in folate levels

Ford et al. (2008) failed to show a benefit of supplementary folic acid.

Question 28

Disordered folate metabolism and depression

those with a faulty gene….

Answer 28

Those with the faulty gene have up to 70% REDUCTION IN ACTIVITY

Question 29

Dietary patterns and mood
Dietary patterns and depression…

Answer 29

Sanchez-Villegas et al. (2009) suggests that a Mediterranean dietary pattern confers protection against the development of depression.
Adherence to the Mediterranean diet was categorized into quartiles, with incremental increases in risk for depression associated with lower adherence.
Compared with those on lowest adherence to the Mediterranean dietary pattern, those with the highest adherence had a substantially reduced risk of depression (HR = 0.58).

A meta-analysis (Lai et al., 2014) showed that a healthy dietary pattern (high intake of fruits and vegetables, fish and wholegrains) is associated with a reduced odds ratio for depression.