Environment and the Brain (COMPLETE SET)

Regulations on furniture flammability

• 1977 - Woolworths Manchester Burned down → introduced flame retardants

  • polyurethane foam in stuffing was highly flammable

• Reduced fire related deaths

• UK (and a few other EU countries) have regulations covering furniture flammability

  • GPSD → General Product Safety Directive

  • EN Standards → especially EN 1021 and EN 597

Flame retardants

• example

• mechanism

• biological issues

• Bromodiphenyl ether (BDE-47)

• Halogenated compound which thermally decomposes to release bromine free radicals

• halogen free radicals can then quench radicals which sustain combustion (H, OH and O free radicals)

  • This stops the fire

• Poor biodegradability → bromine not found in environment so not used naturally or digested by enzymes so persists in environment and organisms

• Lipophilic → not water soluble

  • can cross BBB and accumulate in body fat

  • LogP ~ 6

• present all over world

Structure of BDE-47

Forever chemicals

• Persistent organic pollutants (POP)

• Bioaccumulates → persist in the environment for long periods of time

• Half-life of days/years in humans

• Often contain halogens (Br and Cl)

• Present from poles to equator

  • In natural environments (especially water)

  • in organisms (mammals, fish, birds) → gets into food chain

  • in people → found in 100% of 298 human milk samples (Canada. 2008-11)

  • in buildings and vehicles

• Includes flame retardants

Half-life of brominated compounds

• Half-life of BDE-47 is around 664 days (1.8 years)

  • time for concentration to half

• This is the time for elimination in the absence of further uptake

• follows exponential decay

• time for elimination varies with diet and metabolism

• decay from systemic circulation results in continuous exposure to the nervous system

• Can be much longer in other compounds

BDE-47 systematic reviews and meta-analysis

• how

• findings

• collation of data from several studies, with adjustment for major confounders (maternal education, income, smoking, alcohol, home environment, breast feeding)

• BDE-47 in maternal blood, child blood and breast milk measured

  • Blood BDE-47 up to 1470ng/g of lipid

  • Breast milk BDE-47 up to 200mg/g lipid

• BDE-47 in infants is associated with decrements in motor development, cognitive development and attention-related behaviours

  • IQ decreased by 3.7

    • 3-6 points decrease per 10 fold IQ decrease

  • Prenatal exposure is the strongest predictor

  • limited association with ADHD

• Exposure begins in-utero by breast feeding

Mechanisms of BDE-47 in neurobiology

• studied by in-vitro and in-vivo studies

• looked at Cerebellar granule neurones involved in motor learning, coordination and sensory processing

• effects on mouse neurones:

  • alters signal transduction

  • oxidative stress

  • apoptosis

• Increases reactive oxygen species (ROS) and reactive carbonyls

• decrease cell viability

• increase apoptotic markers (Caspase-3)

Limitations of using animal studies in BDE-47 studies

• In-vivo duration and dosage

  • micromolar over days

  • doesn’t represent human exposure

• In-vivo tissue concentration

  • hard to compare to humans as they are an order larger

• studies are post-natal not in-utero

• No behavioural follow up → learning, memory, motor function

• ROS production is a causal factor in the neuronal dysfunction caused by BDE-47

International legislation and mitigation for flame retardands

• mitigation and legislation consensus published in Environmental International in 2023

  • UK has highest use

  • unsure of whether and to what extent flame retardants contribute to fire safety

  • flawed tests for fire safety (eg. ignition test)

  • recommendations:

    • minimise use

    • use less combustible materials

    • evaluate fire risks and therefore need for flame retardants

    • promote culture which considers environmental impact

• implications of global health

• prognosis for future generations

UK legislation (2025)

• PBDE regulations (poly-BDE)

  • tetra-, penta-, hexa-, hepta- and deca-BDEs

  • manufacture and sales banned

• Waste containing PBDEs

  • destroy or irreversibly transform

• Electronics

  • Max 0.1% PBDE content

• Water/envrionment

  • classified as priority hazzardous pollutants

  • ongoing surevilance

• Waste mannagement

  • no recycling avove POP limits

  • mandatory destruction by incineration for water exceeding threshold

  • strict control of old electronics, foams, textiles and plastics

what is LogP?

• a quantitative measure of lipophilicity or ability to dissolve into lipid, fat or oil

• eg. beta-carotene is highly lipophylic

• -ve is hydrophylic

• 0 is equaly water and fat soluble

• +ve is lipophylic

How is logP calculated?

• determined by online modelling or experimentallty

  • measure distribution of a coumpound in a beaker of water and oil (1-octanol)

• Henry’s Law → Kp = conc in oil / conc in water

  • P = [octanol]/[H20]

  • use logP as numbers are large

    • LogP = Log₁₀ ([octanol]/[H20]) at a given pH

      • more lipophilic → more in oil so higher Kp

• [fat] = [H20] 10^logP

Trichloroethylene TCE LogP

2.2

Rotenone LogP

3.34

Paraquat logP

-6.7

Fat repositorys for lipophiles

• white fat is lipophylic and so absorbs fat soluble compounds

  • fat soluble vitamins → D and A

  • organic pollutants → BDE, herbicides, pesticides

  • gases → anaesthetics

  • drugs → clinical and recreactional

    • eg. THC in weed → logP 6, found in fat for 2-3 months in long term users

• loss of white fat mobilises lipophilic compounds → exercise, starvation, weight loss, breast feeding

BDE on myelin

• myelin acts as a repository for lipophilic compounds such as BDE-47

• lopophiles accumulate around myelinated brain structures → white matter

• Disrupts myelin sheath formation

  • study using zebra fish embryos

    • loss of oligodendrocytes in hindbrain

    • loss of cells was dependent on BDE dose

lipophile disribution in mice brains

• accumulate around white matter

• radiolabeled hexachlorophene (HCP) has simila log P to BDE (5.5)

  • use as surrogate for BDE-47 → use to image uptake

  • uptake in whole brain but especially neck fat and heavily myelinated areas → corbis callosum, nerve bundle and trigeminal nerve

Distribution of lipophiles in the nervous system

• CNS → white matter

• ANS

  • pre-ganglionic neurones → thicker myelin

  • post-ganglionic neurones → thin or no myelin

• PNS

  • A delta, gamma, beta and alpha fibres all have myelin

  • C fibres → no myelin

• thought that BDE accumulates in myelinated fibres, especially Abeta and Aalpha as they have the thickest myelin

LogP and BBB penetration

clinical use of morphine

• gold standard analgesic

• acts on u-receptor

• effective → especially in new users

• causes euphoria, and dysphoria in chronic users

• causes tolerance → need more for same response in repeat users

• can develop dependence

• can cause constipation → main side effect

• antitussive → stops coughing

drug use distribution in the Americas

• opioids mostly in USA

effects of drugs on people → disorders, deaths and treatment

link to environment

• most abused drug is marijuana and then opioids

• opioids causes most deaths → alters respiratory function, increasing dose increases risk

• high number of opioid users need treatment

• numbers suggets that there will be cannabinoids and opioids in the environment

Opioid crisis

• escalation of use of perscription opioids

• increasing overdose deaths

• increased production of synthetic opioids of high potency

• prescriptions are decreasing but synthetic use ios increasing

environmental impact of drug cultivation and production

• eg. packaging of morphene has biggest effect

waterway testing in drug research

• testing drug content in water ways → determine what and how much is being used

• can then assess the environmental effects

• eg. glastonbury → lots of MDMA

drug concentrations in waterways

• drugs enter water via several means

• water treatment can alter drugs

• water can enter soil and influence the wider environment (and food)

why is detection of drugs in waste water important?

• understand what drugs people take and where

• identify drug trends and new substances

• usefull for public health → easier to support overdoses

• very low concenrations of synthetic opioids can be detected → down to 0.01ng/L

• used to sample Covid19 infection hotspots → identify asymptomatic hotspots

• 74% of uk population is under water survaillance

• allows harm minimisation and warnings to users → cost effective way to monitor and evaluate response to inverventions

fentanyl and soil

• fentanyl exposed to water and soil

• is very immobile in environment → persisted for over 7 weeks

• has a long term environmental impact

different types of opioids in water

• several types in waste and surface water

• varied efficacy of removal from water across countries

• most common → morphine and its metabolites (codine, dihydrococdeine, oxycodone and tramadol)

• methadone → used to reduce opioid dependence

• tramadol → long term pain management

issues with water treatment plants

• treatment can increase drug levels in the water

• metabolises compounds and can change their structures

• eg. fentanyl is metabolised into other drugs

• high levels of tramadol and its metabolites

opioids in surface water

• can impact wildlife

• tramadol and its metabolites most abundant

• also morphine, codene and methanadone metabolites

opioids in tap water

• methanadone and its metabolites most common

opioids in food

• in musssels

• used to monitor pharmaphseitical levels in water → found antidepressants, drugs etc

• filter water so take them up

• study bioaccumilation

• found that this was not a hazzard (have to eat lots to have an effect) → but does show

envrionmental risks of opioids in water

• study exposure on models eg. zebrafish → look at environmental impact

• study mechanisms relevant to human disease and disorders

• study life cycles of organisms

• study combinations of drugs which enter water and different concentrations

reuction stratagies for drug water pollution

• education on what to do with unused drugs → drug return programmes

• eg. deactivation bags in the US for perscribed opioids

what is a parasite?

• an organism taht lives in or on its host and survives off or at the expense of the host

• can be:

  • protozoa → one celled

  • helminths → multicellular parasitic worms

  • ectoparasites → live on external surface of host eg. flea, tick, mosquito

  • fungi

definitive host

• hosts that the parasite reaches maturity within and can then reporoduce

intermediate host

• host that harbours sexually immature parasites

hosts as vectors

• living organism which tranmits parasites between humans or animals

• often blood sucking eg. mosquito

toxoplasmosis

• toxoplasmosis gondii

• single celled parasite

• most common human infection

• can stay in body for lifetime

• few have symptoms

• dangerous in pregancy and compromised immune system

  • why pregnant women cannot eat certain foods or clean cat litter trays

  • can test some women as they are not at risk if they are already infected

toxoplasmosis life cycle

• cats are definitive hosts

• unsporulated oocysts in cat faeces

• sporulate and become infective

• intermediate hosts (birds and rodents) eat material containing oocysts

• oocysts transform into tachyzoites after ingestion → invade neural and muscle tissue

  • develop into bradyzoites

• cats consume intermediate host and become infected

• animals bred for meat can also become infected with tissue cysts (intermediate hosts)

  

human toxoplasmosis infection

• eat undercooked meat

• drink infected water

• contact with infected cat facaes

• contaminated soil

• congenital (mother to child) infection

• infected organ transplant or blood transfusion

toxoplasmosis infection symptoms

• most are asymptomatic

• moderate flu → swollen lymph glands or muscle aches

• severe → damage to brain, eyes and organs

  • more likely if weak immunesystem

• ocular toxoplasmosis → reduced vision, blurred vision, eye redness

• infection at birth → no symptoms until later in life

  • small number have severe eye and brain damage at birth

toxoplasmosis in the brain

• reduced fear, increased impulsiveness → more likely to be preyed upon

• can cross BBB

• linked to: schizo, bipolar, depression, road traffic accidents, brain tumours, suicide and risk taking/entrepenurial activity

toxoplasmosis invading the brain

• tachyzoite spontaneously differentiates into bradyzoite form in muscle and neural cells

• latent bradyzoites persist and can reactivate into virulent tachyzoites

  • cause encephalitis → mostly in immunocompromised hosts

• persists in neurones → lifelong slow replication

toxoplasmosis and changes to the brain

• cysts express tyrosine hydroxylase and dopamine → 3x increase in DA, increase risk taking

• manipulate Ca2+ signalling → silences neurones

• blocks apoptosis

• loss of neurogenesis

• loss of synapses

• low grade neuroinflammation → activated microglia and astrocytes, neurodegeneration

Naegleria fowleri

• brain eating amoeba

• live in warm fresh water and soil

• grow in warm conditions → up to 46 degrees C

how does Naegleria fowleri enter the body

• enters via nose

• destroys beain tissue → causes primary amebic meningoencephalitis (PAM)

• almost always fatal

Naegleria fowleri forms

• in challenging conditions (eg. below 10 degress or scarce food) → cysts

• trophozoite stage → actively feeds and replicates, develops food cups or suckers

• flagellated form → change in ionic concentration causes change back to trophozoit stage

Naegleria fowleri in the brain

• flagellated form inhaled in water

• attaches to nasal mucosa

• passes normal immune defences

• analogies of ACh recepors → ACh is a stimulus

• move alomg olfactory nerve via cribiform plate to olfactory bulbs

• enter trophozoite stage → eat neurones and astrophages using food cups

• release cytolytic molecules → acid hydrolases and phospholipases

• destroy tissue

• cause immune response by activating innate immune system → macrophage and neurophil infiltration

• swelling → intracranial pressure

• death

malaria prevelance and impact

• 4 african countries (nigeria, DRC, tanzania and niger) account for half maleria deaths

• 40% of health budget spent on malaria in some countries

• 619,000 die a year

• 80% of deaths are children under 5

types of malaria parasite

• plasmodium falciparum → responsible for most deaths

• plasmodium vivax and plasmodium ovale → have dormant liver stages which cause relapses months or years after contraction

• plasmodium malariae → chronic lifelong infection of untreated

• plasmodium knowlesi → parasite in monkeys in south east asia, severe and somtimes fatal in humans

malaria lifecycle

• mosquito host parasites motile sporozoites

• when bitten they enter the bloodstream and go to the liver

• asexually reporoduce in liver into merozoites

• infect blood cells and burst blood cell → spreads more

• develop into gametes → transfered to mosquito when bitten again

  

progress in malaria management

• many countries have now been certified malaria free

• there is progress but some areas still have lots

malaria vector

• female anopheles mosquitos

malaria symptoms

• most asymptomatic

• small number develop severe malaria

• cerebral malaria → life threatening complication of severe malaria

  • 20% fatality

  • causes neurological impairments

  • can develop at any age

• children over 5 are most at risk

classic malaria

• lasts 6-10 hours

• cold state → cold, shivering

• hot stage → fever, headache, vomiting, seizures in children

• sweating stage

• stages come im waves every 12-48 hours as new parasites are released into blood

• can relapse years later → dormant parasites in liver

• can trea with antibiotics if recognised early

severe malaria

• severe anasemia → destroyed RBCs

• Hb in urine

• acute respiratory distress syndrome (ARDS) → inflammatory reaction in lungs

• abnormal blood coadulation

• cardiovascular collapse

• acute kidney injury

• hyperparasitemia → malaria parasite infects over 5% of RBCs

  • metabolic acidosis → cannot metabolise ATP

  • cerebral malaria

cerebral malaria symptoms

• coma

• seizures

• neuroinflammation

• post-malaria neurological consequences

  • long term cognitive deficits

  • epilepsy

  • impaired hearing ability

  • sensory disorders

  • motor weakness

brain pathology in cerebral malaria

• obstructed mucrovasculature → adhesion of plasmodium infected RBCs to endothelial cells, causes hypoxia and oedema (swelling by water entry)

• inflammatoon → excessive pro-inflammatory cytokine production

• loss of endothelial barrier integrity increases BBB permeability → loss of brain homeostasis, worsens oedema and small haremorrhagic events eg. mini strokes

• 

brain in non-cerebral malaria

• still has some changes

• oedema and blood markers of brain damage (eg. glial proteins)

treatment of malaria

• prevention → mosquito nets, repellents, removing stagnant water, lomg sleeves and anti-malaria drugs

• vaccines

  • RTS,S/AS01 → allready rolled out but supply doesnt meed demand

  • R21 → approved, easier to make

  • both aginst P.falciparum → most common

    • safe amd effective in preventing malaria in children in clinical trials

Taenia solium

• pork tapeworm

• humans are the definitive host

• cause neurocysticerosis → cysts in brain

• causes headachees and seizures

• cysts in brain, muscles and eyes

• only infected from eggs in human faeces, not from pork

taenia solium life cycle

• human eats undercooked infected pork → gets tapeworm

• tapeworm released in faeces → eggs or parts of worm get into environment → no cysts just from worm

• infection via eggs or parts of worm in faeces and environment → cysts

  

climate change and parasites

• many infectious diseases are climate sensitive

• warmer climates are expam#nding the areas were vectors can survive

• increased rainfall, floods ans drought creates stagnant water → breading and risk of water contamination

• extree weather events disrupt infrastructure and health symptoms → increased vulnrabiloty to infection

• migration, urbanisation and deforestation impact spread

• escelation is worse → need climate intervention now

climate change on vector-borne disease

• more places suitable for vectors → warmer temperatures and increased rainfall makes more breeding areas and droughts form pools of stagnant water

• warmer climate extends disease transmission season

• temperature change affects vector behaviour → change biting behaviour so nets are less effective

fungal infections on the brain

• fungal meningitis → meninges become inflammed, more common in weakened immunesystem

  • HIV

  • cancer

  • steroids

  • immunosuppressants

• rare

odds ratio of pesticide exposure and PD

• use retrospective study → odds of those who had previously been exposed to pesticides

  • large chance of PD if exposed to pesticides → OR of 1.94

    • PD patients 2x more likely to have been exposed to pesticides

• prospective study → 1.7 fold increased relarive risk of PD with pesticide use

Parkinsons disease

• progressive neurological condition

• symptoms → tremor, slow movement, muscle stiffness

• risk → increased age, 1.5x more in males, genetics, environmental (head injury, pesticide and herbicide exposure and chlorinated solvents)

• pathology → loss of DA neurones in substantia nigra pars compacta in midbrain → nigrostriatal pathway is impaired (motor feedback control)

Rotenone

• netural product → in tropical and subtropical plants, especially gena Derris

• lipophilic → LogP = 3.3, so can cross BBB

• potent → IC50 is 1-10nm

• imhibits complex 1 of mitochondrial electron transport chain

• used in pesticides → insects eg. weevils, beetles and flies

• used to clear lakes of invasive fish (piscicide)

• environmental half life of days

• associated and causal agent of PD

mechanism of rotenone

• complexes of electron transport chain pump H+ across the membtane to power the priduction of ATP

• rotenone blocks the transfer of electrons in complex 1 → cannot produce ptoton gradient so no ATP is produced

• generates reactive oxygen species (ROS) which activate apoptosis by geberation of caspase 3

• can cross BBB

• apoptosis of cells in substantia nigra and decreased ATP of these cells

• kills dopaminergic cells → parkinsonism

• rotenone is selective for the substantia nigra → unknown why, dopamine metabolism?

effect of rotanone on DA metabolism

• decreases ATP, so decreased VMAT DA uptake → increased cytosolic DA

• MAO oxidises DA to DOPAL → increase cystolic DOPAL

• increased ROS decreases ALDH enzyme activity so decreases DOPAC production → build up of cytosolic DOPAL

• DOPAL fixes the cell and causes apoptosis → specific to substantia nigra neurones

casscade of intrinsic apoptosis

• ROS are generated

• causes mitochondrial damage

• opens mitochondrial permeability transition pore → hole in the mitochondrial membrane

• collapse of mitochondrial membrane potential, loss of membrane and matrix proteins

• release of cytochrome C into cytosol → activates Apaf 1 (apoptotic protease activating factor 1)

• apoptosome forms

• caspase enzyme activation → procaspase 9 activates executioner caspases (3, 6 and 7)

• execution phase → DNA fragmentation, degredation of cytoskeleton proteins and formation of apoptotic bodies

  

interventions regarding rotenone

• evidence for association with PD and mechanistic cause of neurodegeneration

• banned in 2009 in UK

• banned in USA, EU and switzerland

• environmental half life of days → photodegredation

  • permitted for some things → piscicide

paraquat use

• man made oxidant

• herbicide

  • 1950s

  • cheap

  • increased food productivity and weed control

  • used on 100s of crop types, mostly plantation crops → maize, organges, tea, coffee, palm oil, sugar cane

  • USA use troppled 1992-2018

paraquat toxicity

• only associated with PD, not causal → no causal mechanism

• strong comercial interests and is still exported worldwide

• is a systemic poison

• half life → >7 years

• contaminates soil and water

• no antidote to poisoning

LogP of paraquat

• LogP = -6.7

• hydrophilic → cannot cross BBB

• acts like rotenone on isolated mitochondria but cannot enter brain its self

• could enter damaged BBB or be metabolised to something which can

paraquat and PD

• odds ratios from meta analyses

• OR of 1.64

• correlational, not causal

forrest plots

• use in meta analysis

• plot means and weights of odds ratios

• calculate mean OR

confounders in the link between PD and paraquat

• exposure to other pesicides

• male

• smoke

• farmers

• farm animal exposure

• living on a farm

• drinking well water

• living in rural area

legistaltion surrounding paraquat

• banned in 68 countries

• banned in UK in 2007

trichloroethylene (TCE)

• solvent

• volatile colourless liquid

• logP = 2.2 → lipophilic

• used to extract fat soluble compounds

• uses:

  • paint remover

  • degreaser

  • decaffinating coffee

  • dry cleaning

  • carpet cleaning

  • anaesthetics → trilene, banned 1977

• persists in environment → halogenated forever chemical

• found in water, food, fat and breast milk

• associated with PD

studys on solvent (TCE) exposure

• cohort study of US army vererans

  • increased PD incidence in one camp over another (OR was 1.70)

  • this camp has TCE contamination in the water supply → from water runnoff from decreasing and cleaning machinery

  • ingested in food, water and bathing water

  • associated with PD and no other neurological condition

• twin studies

  • one had PD and one didnt

  • interviewed on pervious work

  • increased PD development of worked with degreaser

  • association not causation

TCE animal study

• rat models → replicate in weeks what takes years in a man

• high dose of TCE oraly dosed for 6 weeks

• measured mitochondrial bioenergetics

  • use mitochondria from substantia nigra and compared to striatum and liver as controls

• changes in bioenergetics seen only in substantia nigra

• selectively inhibited complex 1

TCE mechanism

• inhibits complex 1 to blovk the electron transport chain, oxygen consumption and ATP production

• like rotenone

nigrostriatal DA histochemistry after TCE

• loss of tyrosine hydroxylase in neurones in substantia nigra pars compacta after TCE treatment (A control vs B TCE)

• loss of retrograde labelled fluorogold dopaminergic neurones in substantia nigra pars compacta (C control vs D TCE)

TCE mechanism in relation to parkinsons

• has candidate toxic metabolites → DCVC, TaClo and TACH (inhibits ALDH)

current use of TCE

• degreasing

• chemocal feedstock

• textiles

• dry cleaning

• military (reduced)

• no longer used in:

  • anaesthetic

  • decaffination

  • animal feed processing

• enters environment via industrial processes leaching into water supply

TCE in in human breastmilk

• women with lower BMI have highest breastmilk TCE concentration

• fat is protective → leeches TCE

• not replicated and small sample

TCE legislation

• regulated

  • america → centre for disease control

  • europe → european chemical agency

• still advertised

• ban on domestic use in EU

• organic alternatives available

diets that are good for the brain

• mediterranean diet

• anti-inflammatory diet

diets that are bad for the brain

• ultra-processed foods

ketogenic diet and what it does

• high fat, low carbohydrate, controlled protein intake

• used to treat drug resistant epilepsy → mostly for children, sometimes for adults

  • treats GLUT1 deficiency

  • doesnt work for all

  • must be carefully monitored

• changes body energy source from carbohydrates (glucose) to fats (ketones)

  • increases mitochondrial function and biogenesis

  • reduces oxidative stress

  • changes gut microbiome so impacts GBA

  • mediate neuroinflammation

  • change gene expression

    • mediated by circulating miRNA and other epigenetic molecules

molecular impact of ketogenic diet

• downregulation of genes

  • KCNJ12, SLC22A3 and KCNA10 → ion channels, indirect impact on epilepsy

  • MAO-A, HCRT1 and HCRT2 → neurotransmission, dopamine and sleep regulation (orexin genes, produced when awake)

  • PRKCG, GNG10 and BSN → synapse strucure

• upregulated genes

  • CACNA1C → ion channels

  • CDH2, FGF12 and DOC2A → synapse structure

  • BDNF → synaptogenesis and adult neuronal stem cells

ketogenic diet for GLUT1 deficiency

• GLUT1 → expressed on erythrocytes and BBB endothelial cells

  • facilitates glucose transport across BBB

• deficiency

  • low CSF glucose levels for brain energy

  • developmental delat movement disorder with generalised intractable epilepsy

• keto diet provides alternative brain energy source → ketones cross BBB via MCT1 transporter

Ketogenic diet metabolic pathway

• fats are eaten

• converted to ketone bodies in the liver (astrocytes can also produce ketones)

• these cross BBB via MCT1 transporter

• ketone bodies enter neurone and are digested into 2x acetyl molecules

  • give 2x energy as glucose

• used in TCA cycle to give energy without need for GLUT1

what is included in the mediterranean diet

• lean protein, plant based foods and healthy fats

  • seafood

  • fruit and veg

  • whole grains

  • nuts and legumes

  • good oils (olive, avocado, nut)

  • water and some wine

mediterranean diet and depression

• meta analysis shows a small decrease in odds ratio with depression

• did the same with alternative healthy eating index → similar effects

anti-inflammatory molecules in helathy diets (mediterranean)

• omega-3 polyunsaturated fatty acids → seafood

• unsaturated fatty acids → olive oil

• polypgenols → cocoa, blueberries, curcumin and tumeric

• dietary fibre → in whole veg and wholemeal products