Seven Scientifically Proven Anti-Inflammatory Strategies for Today’s Modern Mental Health Practice

A Brief Introduction

What’s so bad about inflammation?

What Do We Mean by Increased Inflammation in Psychiatric Conditions?

NormalHealthy

PsychConditions

AutoImmune

AcuteInfection

Incr

easi

ng In

flam

ma

tion

The “Truth” about Depression as an Inflammatory Condition

Kling MA, et al. Biol Psychiatry. 2007;62(4):309-313.

What’s So Bad about Mildly Increased Inflammation When Chronic?

Miller AH, et al. Nat Rev Immunol. 2016;16(1):22-34. Puzianowska-Kuznicka M, et al. Immun Ageing. 2016;[Epub ahead of print]. Krishnamoorthy S, et al. Cancer Metastasis Rev. 2006;25(3):481-491. Mueller K. Science. 2013;339(6116):155. Shacter E, et al. Oncology. 2002;16(2):217-226. Hu FB, et al. Diabetes. 2004;53(3):693-700.

Chronic mild inflammation today increases the risk of the following in the future:

• Major depression

• Posttraumatic stress disorder (PTSD)

• Premature aging

• Cardiovascular disease

• Stroke

• Diabetes

• Cancer

• Dementia

Anti-inflammatory Strategy #1

Probiotics

Probiotics and MDD: Quite the Buzz

MDD = major depressive disorder.

Brave Mice and Timid Mice

Collins SM, et al. Curr Opin Microbiol. 2013;16(3):240-245.

NIH Swiss = “bold”

BALB/c = “anxious”

Transfer of Microbiota Transfers Behavior between Mouse Strains

BDNF = brain-derived neurotrophic factor.Bercik P, et al. Gastroenterology. 2011;141(2):599-609.

BALB/CNIH Swiss

NIH Swiss Fecal Transplant

Increased hippocampal BDNF

Transfer of Microbiota Transfers Behavior between Mouse Strains

Bercik P, et al. Gastroenterology. 2011;141(2):599-609.

BALB/C NIH Swiss

BALB/C Fecal Transplant Decreased hippocampal BDNF

Depression May Be (Partly) a Matter of “Gut Feelings”

Zheng P, et al. Mol Psychiatry. 2016;21(6):786-796.

The gut microbiotas of 58 medically-healthydepressed individuals were compared with thoseof 63 matched controls. Depression wasassociated with increased Actinobacteria anddecreased Bacteroidetes, and increased anddecreased operational taxonomic units withinFirmicutes. Transplantation of microbiota fromdepressed individuals to germ-free mice produceddepressive- and anxiety-like behavior comparedto transplantation of microbiota from controlparticipants.

Probiotics Reduced Negative Emotionality in Normal Volunteers

Messaoudi M, et al. Brit J Nutr. 2011;105(5):755-764.

In 55 medically-healthy volunteers a probiotic formulation of Lactobacillushelveticus and Bifidobaceterium longum R0175 taken for 30 daysreduced depression, anxiety, and other negative emotions whencompared to placebo. But note that baseline scores on these items werelow and differences between groups were modest.

Probiotics May Reduce Anxiety But Not Depression in Chronic Fatigue Syndrome

BDI = Beck Depression Inventory; BAI = Beck Anxiety Inventory.Rao AV, et al. Gut Pathog. 2009;1(1):6.

In 39 participants with chronic fatigue syndrome randomized to L caseistrain Shirota vs placebo, 8 weeks of probiotic treatment increased stoolsamples of beneficial bacteria and was associated with a reduction inanxiety but not depressive symptoms.

Probiotics May Improve Symptoms in MDD

HOMA = homeostatic model assessment; IR = insulin resistance; hs-CRP = high-sensitivity C-reactive protein; GSH = glutathione.Akkasheh G, et al. Nutrition. 2016;32(3):315-320.

40 participants with major depressive disorder randomized to 8 weeks ofa probiotic formulation (L acidophilus, L casei, B bifidum) vs placebo.Outcomes included depressive symptoms, CRP, insulin sensitivity, andantioxidant capacity.

Web Site for Probiotic Formulations

http://usprobioticguide.com/

Birth by C-Section: An Anti-probiotic Strategy Par Excellence

Thavagnanam S, et al. Clin Exp Allergy. 2008;38(4):629-633. Pistiner M, et al. J Allergy Clin Immunol. 2008;122(2):274-279. Huh SY, et al. Arch Dis Child. 2012;97(7):610-616. Sevelsted A, et al. Pediatrics. 2015;135(1):e92-e98. Blustein J, et al. BMJ. 2015;350:h2410.

Birth by C-Section produces a profoundchange in the infant microbiota, characterizedby reduced maternal vaginal flora and increasedskin flora.

Birth by C-Section is associated with anincreased risk of asthma, allergic rhinitis,childhood obesity, systemic connective tissuedisorders, juvenile arthritis, inflammatory boweldisease, immune deficiencies, leukemia andtype 1 diabetes.

Exposure to Maternal Vaginal Fluid Normalizes Microbiota of C-Section Babies

Dominguez-Bello MG, et al. Nat Med. 2016;22(3):250-253.

Anti-inflammatory Strategy #2

Calorie Restriction/Intermittent Fasting

Methods of Eating Less

Michalesen A. Curr Pain Headache Rep. 2010;14(2):80-87.

Fasting/Calorie Restriction May Improve Mood and Reduce Anxiety

Fond G, et al. Psychiatry Res. 2013;209(3):253-258.

Similar Physiological Benefits for Exercise and Intermittent Fasting

Van Praag H, et al. J Neurosci. 2014;34(46):15139-15149.

24-Hour Fast Decreases NLRP3 Inflammasome Activity

Traba J, et al. J Clin Invest. 2015;125(12):4592-4600.

In 19 healthy volunteers, a 24-hour fast reduced NLRP3 inflammasome activity and resultant release of inflammatory cytokines compared to the refed state. The effect of fasting was mediated by sirtuin augmentation of mitochondrial integrity. Feeding also increased endotoxin in the circulation.

• Set realistic goals• Attempt to reduce daily

calorie intake by 10% initially, if successful consider increasing to 25% depending on food intake at baseline

• Hydrate aggressively• Time the calorie content

of your meals to match natural hunger cycles

• Do not over-restrict

• Experiment with brief fasting periods first (ie, 12 hours)

• Restricting intake to 300 to 500 calories on fasting days quite effective

• If successful consider up to 24 hours of fasting with nothing but water

• Try fasting at least 2 days per week

Specific Suggestions on Utilizing this Anti-inflammatory Strategy

FastingChronic Calorie Restriction

Anti-inflammatory Strategy #3

Sleep Away Your Inflammation

Autonomic, Endocrine, and Immune Imbalance in Insomnia

Irwin MR. Psychiatr Clin N Am. 2011;34(3):605-620. Irwin MR. Annu Rev Psychol. 2015;66:143-172.

Associations between environmental stress, life events, and trauma, activation of peripheral inflammation, and increases in central inflammatory signaling, which together are thought to contribute the occurrence of somatic symptoms of pain or hyperalgesia, sleep disturbance, and fatigue.

Metabolic and Immune Consequences of Sleep

Depner CM, et al. Curr Diab Rep. 2014;14(7):507.

0

2

4

6

8

10

19:00 21:00 23:00 01:00 03:00 05:00 07:00 09:00

.

IL-6 May Be Elevated in Insomnia Patients:A Preliminary Finding

IL-6 production is significantly increased in patients with insomnia between 3:00 and 7:00.

*P < .05. IL-6 = interleukin-6. Burgos I, et al. Brain Behav Immun. 2006;20(3):246-253.

Controls (n = 11) Insomniacs (n = 11)

IL-6

(p

g/m

L)

Clock Time

* *

*

Sleep Deprivation and Inflammatory Marker CRP – Reason for Concern

*P = .05 (change from baseline).CRP = C-reactive protein, boundaries of cardiovascular risk.Banks S, et al. J Clin Sleep Med. 2007;3(5):519-528.

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

1 2 3 4 5 6 7 8 9 10

Mea

n C

RP

(m

g/d

L)

Day

Participants undergoing 10 consecutive nights of sleep restriction to 4.2 hours in bed (n = 4)

Participants with sleep restricted to 8.2 hours in bed (n = 5)

*

Highest

High

Mild

IL-6 (ng/mL)

Shift Work May Impact Inflammatory Response

Induced cytokine levels (ng/mL) before the strike (left dot of each line) and after it (rightdot) in 10 anesthesiologists. Presented are IL-6 in which significant decline was evident.The small corner figure provides the mean +SEM across participants. In each of themeasures, the few deviations from the general trend occurred in different participants.

Beilin B, et al. Acta Anaesthesiol Scand. 2006;50(10):1223-1228.

450400

400350

300

250

200

350 150

100

300

250

200

150

100

P = .03

Good Sleep Benefits Inflammatory Response

Study examined the interplay of social engagement, sleep quality, and plasma levels of IL-6 in asample of aging women (N = 74, aged 61–90 years, mean age = 73.4). Sleep was assessed byusing the NightCap in-home sleep monitoring system. The interaction significantly predictedplasma IL-6 levels (β = 1.19, P < .05).

Friedman EM, et al. Proc Natl Acad Sci U S A. 2005;102(51):18757-18762.

-0.4

-0.2

0.0

0.2

0.4

0.6

0.8

1.0

1.2

20 30 40 50 60 70 80 90 100

Pla

sm

a IL

-6 (

log

10

tra

ns

form

ed

)

Sleep Efficiency (cubed; 104)

Sleep and Social Support Interact to Modulate Inflammation

PSQI = Pittsburgh Sleep Quality Index. Tomfohr LM, et al. Psychophysiology. 2015;52(12):1689-1697.

PSQI global scores predicting IL-6 and CRP. The statistical interactionbetween PSQI and social support is shown here using mean social supportand low social support modeled at 1 SD below the mean of the sample.Participants were 67 sedentary men (n = 37) and women (n = 30)

Good Sleep May Mitigate the Pro-inflammatory Effect of Poor Relationships?

N = 1229.Friedman EM. Ann N Y Acad Sci. 2011;1231:23-34.

Top (“high relations”) and bottom (“low relations”) tertiles of scores from the positive relations scale.

CBT for Insomnia May Provide an Enduring Anti-inflammatory Benefit

CBT-I = cognitive-behavioral therapy for insomnia; TCC = tai chi chih.Irwin MR, et al. Biol Psychiatry. 2015;78(10):721-729.

As compared with sleep seminar education active control condition, CBT-I reduced levels of CRP (months 4 and 16, Ps < .05), monocyte production of pro-inflammatory cytokines (month 2 only, P < .05). 123 older adults with insomnia were randomly assigned to CBT-I, TCC, or sleep seminar education active control condition for 2-hour sessions weekly over 4 months with follow-up at 7 and 16 months.

Conclusions

• Sleep disorders and sleep deprivation may be associated with increased inflammatory signaling

• Sleep disorders should be assessed along with other medical and psychiatric disorders at diagnosis and treated simultaneously

• Sleep of adequate quantity and quality may help ameliorate excessive inflammatory tone

• Preliminary evidence suggests that CBT-I may provide a sustained anti-inflammatory benefit

Anti-inflammatory Strategy #4

You Cannot Run Away from Inflammation, or Can You?

Neurobiology of Exercise: A Complex Cascade That Also Involves

Neurotransmitters and Receptors

ANS = autonomic nervous system; CNS = central nervous system; CREB = cyclic adenosinemonophosphate response element-binding protein; CVD = cardiovascular disease; DA = dopamine;ERK = extracellular signal-regulated kinase; 5-HT = 5-hydroxytryptamine; GABA = gamma aminobutyric acid; NA = noradrenaline; ROS = reactive oxygen species; TrkB = tyrosine residue kinasereceptor-type 2; VTA = ventral tegmental area; WAT = white adipose tissue.

Dishman RK, et al. Obesity. 2006;14(3):345-356.

Function DiseaseStructure

Executive ControlsPrefrontal & Cingulate Cortex

Emotional ControlsAmygdala, Prefrontal Cortex

External Input• Visual• Olfactory• Acoustic• Gustatory• Somatosensory

ANS&

Endocrine Systems

DA↓

Parkinson’s Disease

↑ROS

Alzheimer’sDementia

Schizophrenia

Depression

Sleep Disorders

Obesity

Diabetes

CVD

Immune Disorder

IBD, Constipation Colon Cancer

Learning& Memory

Immune Control

Gastrointestinal Control

MuscleCardiovascular Consequences

Metabolic ConsequencesLiver, WAT, Pancreas

Thermal Consequences

Behavior• Social• Sexual• Coping• Addictive• Escape• Fight &

Flight• Stress• Sleep• Ingestive

Motor ControlsMotor CortexStriatum, Brainstem, Cerebellum, Spinal Cord

Motivational ControlsReward,Wanting,SelectionHypothalamus, Accumbens, VTA

Cognitive ControlsHippocampus, Cortex

NeuralPrimary Afferents

“Exercise”

Internal Feedback“Consequences of exercise”

HumoralFactors

CNS

Energy Balance

RepairPlasticityProtectionNeurogenesisTranscriptionNA, 5-HT,GABA, Glutamate, GlycineBDNF/TrkBERK/CREBNFKB

Anti-inflammatory and Cardiovascular Benefits of Exercise

EC = endothelium; NO = nitric oxide; PAI = plasminogen activator inhibitor; PLT = platelet; RBC = red blood cell; sCD40L = soluble CD40 ligand; TF = tissue factor; tPA = tissue plasminogen activator. Chen YW, et al. Ann Med. 2014;46(7):439-455.

Exercise: Effects on Immune System, Skeletal System, Adipose Tissue, and Brain

Pedersen BK, et al. Physiol Rev. 2008;88(4):1379-1406.

IL-6 IL-6

TNF

Sepsis Exercise

Exercise and Cytokines: A Complex Relationship

FFA = free fatty acids; ROS = reactive oxygen species.Fischer CP. Exerc Immunol Rev. 2006;12:6-33.

CONTRACTING SKELETAL MUSCLEGlycogen ROS Calcium

IL-1ra

MACROPHAGESMONOCYTES

T-CELLS

IL-10

ADIPOSETISSUE

FFA

PITUITARYGLAND

ACTH

LIVER

ADRENALGLAND

CRPGlucose

Cortisol

IL-6

Physical Exercise: A Modulator of Inflammatory Cytokines

Nicklas BJ, et al. J Am Geriatr Soc. 2008;56(11):2045-2052.

Not So Fast? Anti-inflammatories May Interfere with Exercise Induced Muscle Protein Synthesis

ACET = acetaminophen; FSR = fractional synthesis rate; IBU = ibuprofen; PLA = placebo.Trappe TA, et al. J Clin Endocrinol Metab. 2001;86(10):5067-5070. Trappe TA, et al. Am J PhysiolEndocrinol Metab. 2002;282(3):E551-E556.

*Significantly different (P < .05) from PLA. PGs have been shown to modulate skeletal muscle proteinmetabolism as well as inflammation and pain. Ibuprofen and acetaminophen inhibit the normalincrease in skeletal muscle protein synthesis after high intensity eccentric resistance exercise. 24males (25 ± 3 yr) were assigned to 3 groups that received IBU (1200 mg/day), ACET (4000 mg/day),or a placebo after 10 to 14 sets of 10 eccentric repetitions at 120% of concentric 1 repetitionmaximum using the knee extensors.

Skeletal muscle FSR

ACET IBU PLA

Exercise May Mitigate Inflammatory Signaling in MDD

107 participants, aged ≥ 40 years

Participation in moderate-intensity physical activity may buffer the risk of higher inflammation often associated with higher levels of depressive symptoms

MIPA = moderate intensity physical activity; CES-D = Center for Epidemiological Studies Depression Scale.Rethorst CD, et al. Psychosom Med. 2011;73(3):265-269.

Exercise Log

www.saundrajain.com/uploads/3/3/5/8/3358541/exercise_log.pdf. Accessed June 28, 2016.

Conclusions and Recommendations

Daley A. J Clin Psychol Med Settings. 2008;15(2):140-147.

• Exercise has an established anti-inflammatory effect thereby promoting general health and well-being, while ameliorating symptoms of psychiatric disorders

• For general health, adults should achieve a minimum of 30 minutes/day, of at least moderate intensity, on ≥ 5 days of the week

Anti-inflammatory Strategy #5

Increasing Socialization

Association between Childhood Social Isolation and Inflammation in Adulthood

Lacey RE, et al. Psychoneuroendocrinology. 2014;50:85-94.

Study used multiply-imputed data on 7462 participants of the National Child Development

Study in the United Kingdom

Socially isolated children had higher levels of CRP in mid-life.

EducationEducation

Adult Social Class

Adult Social Class

Psych DistressPsych

Distress

Obese

Smoke

Obese

Smoke

INCREASED ADULT

INFLAMMATION

Social Isolation(7–11 yrs)

P ≤ .001

Volunteering and Lower Inflammation

Kim S, et al. Gerontologist. 2014;54(5):830-839.

Representative survey of adults aged 57–85 years from the National Social Life, Health, and Aging Project (N = 1790). Study investigates whether productive activities by older adults reduce bodily inflammation.

Productive activities—and frequent volunteering in particular—may protect individuals from inflammation.

CRP by frequency of volunteering, stratified by age groups (including adjustments for all control variables)

Social Network Ties and Inflammation

Yang YC, et al. Biodemography Soc Biol. 2014;60(1):21-37.

Nationally representative sample of adults with a history of cancer (N = 1075) from the National Health and Nutrition Examination Survey III

Lower SNI (Social Network Index) scores showed significantly greater inflammation marked by CRP and Fibrinogen

• Increase Quality and Quantity of Social Connections

• Create / Nurture –Meaningful, supportive, stimulating relationships

• Increase (not decease) macro socialization when early stress is detected

• Text and e-mail connectedness (not to replace macro socialization, but to augment it)

• Do more “chit-chatting” with strangers and people you bump into in a variety of everyday situations

• Smile (a lot)!

Specific Suggestions on Utilizing This Anti-inflammatory Strategy

“Micro” socialization“Macro” Socialization

Want to educate patients about the importance of Social Connectedness?

Tools:

Here are some tools you could utilize –

Access Patient Educational booklet on Social Connectedness here –www.wild5resources.comPassword: wellnessmatters

Want to measure Social Connectedness?

Anti-inflammatory Strategy #6

Enhanced Nutritional Practices

We Indeed are What We Eat: Impact of Our Diets on Inflammation

MAPI = Markers of Adenomatous Polyps I; MAPII = Markers of Adenomatous Polyps II; NSAID = nonsteroidal anti-inflammatory drug. Whalen KA, et al. J Nutr. 2016;146(6):1217-1226.

Pooled cross-sectional study of 30- to 74-year-old men and women in an elective outpatient colonoscopy population (n = 646)

Diets that are more Mediterranean-like may be associated with lower levels of systemic inflammation.

Associations of the Paleolithic (A) andMediterranean (B) diet scores with plasma hsCRPconcentrations, according to selected participantcharacteristics; pooled MAPI and MAPII studies.From an unconditional ordinal logistic regressionmodel; only the comparison of quintile 5 relative toquintile 1 of each diet score with the sex-specificquintiles of the biomarkers is shown. Modelcovariates included study (MAPI or MAPII), regularNSAID or aspirin use ($4 times/wk), age, totalenergy intake (kilocalories), current hormonereplacement use (in women), sex, smoking(current or former and never), BMI (in kg/m2;categorized by WHO criteria into underweight,normal, overweight, and obese), education level(no college education or some college education),physical activity level (high or low based on themedian weekly metabolic equivalent task–h/wkexpenditure in the pooled population), regularmultivitamin use ($3 times/wk), and season of theyear the FFQ was completed. hsCRP iscategorized into sex-specific quintiles from thepooled study population. P-trend was calculatedby assigning the median of each diet score quintileto each quintile, and treating this quintile exposureas continuous. For each quintile of each dietscore, eb is the odds that the biomarkerconcentration is greater than the quintile cutoff ifthe diet score is in the nonreferent categorycompared with the odds if it is in the referentcategory.

Are We What We Eat? Emerging Scientific Data on Nutrition and Health (Risks/Benefits)

Fardet A, et al. Nutr Rev. 2014;72(12):741-762.

Review of 304 studies examining the link

between nutrition and chronic diseases (mental health, obesity, skeletal health, cardiovascular

disease, cancers)

Radar plots for food groups and beverages vs

number of references (percentages from 0%–

100% shown on concentric circles)

showing protective(solid green lines),

neutral (dashed yellow lines), or deleterious

(dotted red lines) effects towards all diet-

related chronic diseases

• Data supports following micro-nutrients as antidepressants and as anti-inflammatories

– Vitamin D

– L-methylfolate

– SAMe

– Omega-3 fatty acids

• Sugars/Simple carbs = OUT

• ↑ Vegetables! By a lot

• ↑ Nuts! By a lot

• ↑ Fish! By a lot

• Moderate red meats

Specific Suggestions on Utilizing This Anti-inflammatory Strategy

“Micro” Nutritional Changes“Macro” Nutritional Changes

Tools to Incorporate This Anti-inflammatory Intervention into Your Practice

Access Patient Educational booklet on Nutrition here –

www.wild5resources.comPassword: wellnessmatters

Anti-inflammatory Strategy #7

Mindfulness

Meditative Practice & Therapeutic Benefits in Inflammatory Situations (Both Psychological and Physical Stressors)

AA = alpha-amylase; LTM = long-term meditators; MNP = meditation-naive participants; TSST = Trier Social Stress Test. Rosenkranz MA, et al. Psychoneuroendocrinology. 2016;68:117-125.

37 MNP and 31 LTM. Psychological stress induced using the TSST. Cortisol and A, provided measures of magnitude of stress response (samples at baseline and before application of capsaicin cream). Subsequent samples were collected immediately afterthe end of the TSST plus every 10 minutes for the next 40 minutes (total 6 saliva samples).

RESULTS: LTM had lower TSST-evoked

cortisol (P < .05) and perceived stress (P < .01),

Smaller neurogenic inflammatory response (P < .05).

LTM reported higher levels of psychological factors associated with well-being and resilience

LTM practice may reduce stress reactivity and be of therapeutic benefit in chronic inflammatory conditions characterized by neurogenic inflammation

Mindfulness: Acts as an Anti-inflammatory Agent with Exposure to Stressors

MBSR = Mindfulness-Based Stress Reduction (8 weekly 2.5 hourr sessions + 1 full-day session + daily home-based practice, 45 minutes to 1 hour); HEP = Health Enhancement Program (matched MBSR in structure, instructor expertise, and content).Rosenkranz MA, et al. Brain Behav Immun. 2013;27(1):174-184.

Raw cortisol data showing response to the TSST and diurnal cortisol rhythm for each group at each assessment.

N = 49 community volunteers randomly assigned to either MBSR or HEP. TSST used to induce psychological stress and

inflammation produced using topical application of capsaicin cream to

forearm skin.

RESULTS:

MBSR resulted in a significantly smaller post-stress inflammatory response compared to HEP, despite equivalent levels of stress hormones

• Do not just recommend and run! At regular intervals check to see if mindfulness practice is being maintained

• Be a gentle coach. Remind them of the Biological and Clinical studies demonstrating Mindfulness’ benefits

• Recommend increasing practice with early sign of stress

• Teach this – there is “no perfect way to practice mindful meditation.”Teach – “You can’t do it ‘imperfectly.”

• Offer an app / CD• Recommend daily

practice• Amount – short! As little

as 8 to 15 minutes a day is a great start

Specific Suggestions on Utilizing This Anti-inflammatory Strategy

Maintain PracticeInitiate Practice

Want to educate patients about the

importance of Mindfulness?

Tools

Here are some tools you could utilize –

Access Patient Educational booklet on Mindfulness and Audio Files of all the Mindfulness practices here – www.wild5resources.com. Password: wellnessmatters.

Mindfulness Meditations

2 disc CD

WILD 5 Wellness ProgramMindfulness Meditations

Access Patient Educational booklet on Mindfulness and Audio Files of all the Mindfulness practices here – www.wild5resources.com. Password: wellnessmatters.

CD OR DOWNLOAD

Disc One: Tracks 1 through 6:

1. Five-Minute Breathing Space (6:45)

2. Mindful Breathing (15:00)

3. Body Scan (15:00)

4. A Moment of Gratitude (9:58)

5. Happiness Meditation (11:37)

6. Pain Meditation (13:00)

Disc Two: Tracks 1 through 3:

1. Introduction to Mindful Meal Meditation (5:19)

2. Mindful Meal Meditation (23:31)

3. Mindful Moment With A Raisin (9:57)

In Conclusion:

1. For most of our patients (and ourselves) learning to eat less is one of the most powerful anti-inflammatory strategies available

2. Optimized sleep and physical exercise have both demonstrated anti-inflammatory effects and incorporating them into daily practice is critical

3. Practical, actionable recommendations on each of these 7 anti-inflammatory can, and should be offered to our patients. All 7 of these recommendations work through various pathways to improve outcomes