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WHAT DO WE REALLY KNOW ABOUT MEDITATION AND HEALTH?

Osher Mini-Medical School, May 2016Frederick (Rick) Hecht, MDProfessor of Medicine, UCSFDirector of Research, UCSF Osher Center for Integrative Medicine

Does the science live up to the hype?

Through what pathways could mediation impact physical health?

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Cortisol/glucocorticoids have profound effects on the immune system

Inflammatory responses The immune system provides critical defenses

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Risks of a weak immune system The immune system provides critical defenses… but poses dangers

The immune system provides critical defenses… but poses dangers

• Auto‐immune diseases• Allergies• Arteriosclerosis• Aching/pain• Aging

Balance is essential in immune responses

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What are the effects of stress on the HPA axis? 

Trier Social Stress Test

Stress increases ACTH and cortisolDo these connections between 

psychological state and immune system matter? 

Dr. Sheldon Cohen 

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Stress and experimental cold infectionsCohen, et al. NEJM, 1991; 325: 606‐12, 

The autonomic nervous system

Effects of the sympathetic and parasympathetic nervous system

Effects of the sympathetic and parasympathetic nervous system

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Sympathetic neural fibers in lymph nodes

Sloan et al, The Journal of Neuroscience, 15 August 2007, 27(33): 8857‐8865

Social isolation in rhesus macaques changes architecture of sympathetic 

neural fibers in lymph nodes

Sloan et al, The Journal of Neuroscience, 15 August 2007, 27(33): 8857‐8865

What about mental states and health behavior?

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Copyright © 2016 American Medical Association. All rights reserved.

From: Depression and Medication Adherence in Outpatients With Coronary Heart Disease: Findings From the Heart and Soul StudyArch Intern Med. 2005;165(21):2508-2513. doi:10.1001/archinte.165.21.2508

Proportion of participants with and without depression who were medication nonadherent

Summary Three key mind-body pathways

– HPA axis– ANS– Health behavior

Connected with health outcomes Balance of neuroendocrine and immune

systems matters

But what do these pathways have to do with meditation… ?

Mindfulness Moment to moment nonjudgmental awareness of one’s experience cultivated by paying attention. 

‐ Jon Kabat Zinn, founder of Mindfulness‐Based Stress Reduction

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Mantra meditation

• Uses a mantra as a focus• Transcendental meditation

Copyright © 2016 American Medical Association. All rights reserved.

Meditation Programs for Psychological Stress and Well-being: A Systematic Review and Meta-analysis

Goyal et al, JAMA Intern Med. 2014;174(3):357-368.

Mindfulness‐based cognitive therapy is at least as good as medication for depression

Kuyken et al, Lancet, Issue 9988, 2015, 63–73

Changes in cortisol with MBSR?Rosenkranz, et al, BBI, 2013,174–184

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Effects of MBSR on post‐stress inflammatory response

Rosenkranz, et al, BBI, 2013,174–184

What about other immune responses?

SHINE: Randomized, controlled trial

Both groups:• BMI 30 – 45• 6 month active intervention• 18 month total follow-up

Mindfulness-enhanced Group• Mediterranean-type diet info• 500 kcal restriction goal- mindful• 17 sessions • Exercise: 10,000 step/day goal• Mindful eating• Mindfulness stress/emotion

management• Mindful yoga

Standard Group• Mediterranean-type diet info• 500 kcal restriction goal- calorie

count• 17 sessions• Exercise: 10,000 step/day goal• “Filler” Nutrition/Exercise info• Progressive muscle relations

Proportion of participants with 4‐fold or greater flu vaccine responses in SHINE trial 

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

MBSR Control

P = 0.30

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What about ANS responses to stress?

Stress: The good and the bad

ThreatChallengeGood stress

Bad stress

Courtesy of Wendy Mendes

Biopsychosocial model of Threat vs. Challenge Psychophysiology

Under motivated performance, cardiovascular responses distinguish between two profiles:

Approach – Activated (toughness, resiliency) Vs.

Withdrawal– Inhibited (defeat, maladaptive)

(Mendes, 2013)

Appraisal shapes profile

Threat• Demands exceed resources• Constriction of peripheral 

vasculature anticipating wounding (TPR)

Challenge• Resources exceed demands• Cardiac efficiency (CO)

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Δ Total Peripheral Resistance (speech) baseline to post intervention

Δ Cardiac Output (speech)from baseline to post intervention 

Mindfulness and health behaviorHomeostatic eating

Calories out

Physical activityBasal metabolism

Calories in

Food intake

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Hedonic eating

Interaction of homeostatic and hedonic eating

Executive functioning and mindfulness

• Automatic eating behaviors

• Awareness of hunger/satiety cues

• Stress eating• “Surfing the urge”

Change in Fasting Glucose

‐1

‐0.5

0

0.5

1

1.5

2

2.5

3

3.5

0 3 6 12 18

MindfulStandard

Month

Δin m

g/dl

P value = .28 .33 .029 .017

**

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Percent Weight Loss by Intervention Group 

‐6

‐5

‐4

‐3

‐2

‐1

0

0 3 6 12 18

MindfulStandard

Month

Percent w

eight loss 

P value = .34 .19 .09 .21 

^

How helpful was the mindfulness instructor?

TEACHER Mean Std DevA 3.504 0.714B 3.638 0.485C 3.696 0.576

• Rating scale: 1 (not at all) to 4 (very much)• Teacher A vs. others:  ‐0.32, SE = 0.16, p = 0.04• Teacher A vs. B: ‐0.13, SE = 0.11, p=0.23• Teacher A vs. C: ‐0.91, SE = 0.085, p = 0.02

ANALYSIS BY GROUP LEADERIs there evidence of difference effects by group leader?

Weight Loss by Mindfulness Group Leader

‐12

‐10

‐8

‐6

‐4

‐2

0

0m 3m 6m 12m 18m

Percen

t Weight L

oss

Month 

Teacher ATeacher BTeacher C

*F (2, 78) = 3.1, p = .0489 at 18 months

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Weight Loss in Each Arm and Mindfulness Group Leader

‐8

‐7

‐6

‐5

‐4

‐3

‐2

‐1

0

0 3 6 12 18

MF Teacher AMF Teachers B&CStandard

*

Month

Percent w

eight loss 

*ps

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Research team and grant support• Psychology

– Patricia Moran, PhD– Jennifer Daubenmier, PhD– Margaret Kemeny, PhD– Jean Kristeller, PhD– Michaela Kiernan, PhD

• Immunology/HIV– Doug Nixon, MD, PhD– Jeff Milush, PhD– Blake Gurfein, PhD

• Neuroendocrine/Gene expression– Elissa Epel, PhD– Steve Cole, PhD– Roland Stimpson, MD– Jonathan Seckl, MD – Carl Grunfeld, MD– Rob Lustig, MD– Wendy Mendes, PhD– Kevin Laguaro, PhD– Elizabeth Blackburn, PhD– Mary Dallman, PhD

• Biostatistical– Michael Acree, PhD– Peter Bacchetti, PhD

• Imaging/radiology– Sue Noworolski, PhD 

• Diet/NutritionBarbara Laraia, PhD, RD

• Pre/Post‐docs– Sarah Patterson, MD– Sarah Corey, PhD– Ashely Mason, PhD

• Staff– Marcia Guiterrez– Veronika Goldman– Corine Yancey– Janell Vu– Mike Hall

• Participants• NCCAM PO1 P01AT005013 CERC 

and K24 AT007827grant