Slides from my presentation in the Biohacker Meetup in Amsterdam (02-04-2023). What are the vast health benefits of heat alteration, autophagy & calorie restriction and how to incorporate these intelligently into everyday life.

1. THE HEALTH BENEFITS OF HEAT ALTERATION, AUTOPHAGY &
CALORIE RESTRICTION: HOW TO INTELLIGENTLY INCORPORATE
THESE INTO EVERYDAY LIFE
Olli Sovijärvi // M.D., author, co-founder of Biohacker Center
Amsterdam Biohacker Meetup // 02.04.2023 //

2. WWW.RESILIENT-BEING.COM

4. Introduction
• Authors
• Thesis & ethos
• Adaptation as the core of the development of species
• Most resilient beings on this planet
• Mastering resilience
Physical Resilience
• Sources of stress
• Stress sensitivity – Inherited or learned?
• Oxidative stress
• Inflammation
• Energy metabolism
• Ketosis
• Organ systems & stress regulation
• Autonomic nervous system
• HPA axis
• Measuring stress levels & response
• Supplements for resilience
• Technological tools for physical resilience
• Self-care methods for building resilience
Contextual Resilience
Hormetic stressors and hormesis
Immune system
Nature connection
Intermittent fasting & time-restricted feeding
Intermittent energy restriction (IER) & calorie restriction
Heat alteration
Environmental toxins
Longevity
Autophagy
Mental Resilience
• Resilient brain
• Resilient mind & emotions
• Neuroplasticity
• Brain neurotransmitters
• Gut-brain-microbiota (GBM) axis
• Brain foods
• Nootropics
• Psychedelics
• Mindfulness & meditation
• Breathing exercises
• Music, sound, and the brain
• Light and the brain
Social Resilience
• Childhood environment & experiences
• Parenting, attachment & oxytocin
• Personality & character development
• Five-Factor Model for personality types
• Jungian archetypes
• Ego & self
• Shadow & subconscious
• Dark Triad of personality traits
• Trauma & therapies
Spiritual Resilience
• The great chain of being
• Ancestry & heritage
• Consciousness
• Panpsychism & universal mind
• Responsibility
• The Precautionary Principle
• Transcendence
• Immortality
• Constitution of man
• From Wounded Healer to Prometheus
WHAT’S
INSIDE?

5. BIOHACK.TO/HANDBOOK

7. THE MOST SIGNIFICANT
HEALTH CHALLENGES

8. MULTIPLE CHRONIC
DISEASES IN AGING
POPULATIONS
27% WITH MULTIPLE CHRONIC CONDITIONS:
18-44 year old 7%
45-64 year old 33%
+65 year old 64%
Ref: Boersma P, Black LI, Ward BW. Prevalence of Multiple Chronic
Conditions Among US Adults, 2018. Prev Chronic Dis 2020;17:200130
LEADING CAUSES OF EARLY
DEATH AND DISABILITY
1. Ischemic heart disease
2. Low back pain
3. Stroke
4. Lung cancer
5. Chronic respiratory disease
6. Diabetes
7. Alzheimer's disease
8. Headache disorders
9. Falls
10.Drug use disorders
Ref: Global Burden of Disease Study (GBD) 2017

9. SILENT INFLAMMATION
BEHIND DEGENERATIVE DISEASES.

10. SILENT
INFLAMMATION
INCREASES THE RISK OF
GETTING CARDIOVASCULAR
DISEASE & DYING FROM IT

11. INSULIN RESISTANCE
BEHIND CHRONIC
DISEASES.

12. based on lifestyle, medical & technological
interventions informed by science, bioinformatics,
self-quantification, and guided self-experiments.
BIOHACKING
IS HEALTH & PERFORMANCE OPTIMIZATION

13. HEALTH IS TO BE IN BALANCE
IMBALANCE LEADS TO DISEASE

14. HEAT
ALTERATION

16. Native American sweat lodges discovered in Mexico
used by Aztecs 600 years ago

17. TRADITIONAL FINNISH SAUNA

18. HEALTH BENEFITS OF TRADITIONAL FINNISH SAUNA BATHING
Source: Laukkanen, J. & Laukkanen, T. & Kunutsor, S. (2018). Cardiovascular and other health benefits of
sauna bathing: a review of the evidence. Mayo Clinic Proceedings 93 (8): 1111–1121. Elsevier.

19. PHYSIOLOGICAL RESPONSES OF CHRONIC SAUNA BATHING
Ref: Henderson, K. N., Killen, L. G., O'Neal, E. K., & Waldman, H. S. (2021). The Cardiometabolic Health Bene
fi
ts of Sauna Exposure
in Individuals with High-Stress Occupations. A Mechanistic Review. International journal of environmental research and public
health, 18(3), 1105. https://doi.org/10.3390/ijerph18031105

20. ”It is wise to go into the sauna in a fasted state or at
least waiting 4-5 hours after eating before going into
the sauna and avoid consumption of alcoholic
beverages to maximize bene
fi
ts of heat alteration.
Sitting in the sauna with a full stomach not only feels
uncomfortable, but it may cause harmful stress to the
body.”

21. Biochemical functions of HSPs:
• HSPs prevent the accumulation of free radicals (oxidative stress) and
cellular damage
• HSPs repair damaged, misfolded proteins similar to autophagy
• HSPs promote cellular antioxidant capacity
• HSPs are involved in cellular turnover
• HSPs correlate with smooth muscle relaxation and have a significant
role in cardiac myocyte (specialized heart muscle cells) function and
skeletal muscle insulin response (blood sugar regulation)
SAUNA STIMULATES THE RELEASE OF HEAT SHOCK PROTEINS (HSP)

22. FOXO3 PROTEINS & HEAT STRESS
Ref: Fasano, C., Disciglio, V., Bertora, S., Lepore Signorile, M., & Simone, C. (2019). FOXO3a
from the nucleus to the mitochondria: a round trip in cellular stress response. Cells, 8(9), 1110.
• FOXO3 regulates genes that fight cellular aging
(e.g. damage to DNA, proteins, and lipids & loss of
stem cell function)
• FOXO3 also participates in autophagy
• When cells undergo heat stress, FOXO3 proteins
form a complex with sirtuin 1 (SIRT1), which is an
enzyme that influences aging and longevity via
multiple molecular pathways

23. HEAT STRESS ACTIVATES NRF2 PATHWAY
Ref: Otterbein, L. & Foresti, R. & Motterlini, R. (2016). Heme Oxygenase-1 and Carbon Monoxide in the Heart:
The Balancing Act Between Danger Signaling and Pro-Survival. Circulation Research 118 (12): 1940–1959.
Nrf2 (nuclear factor erythroid-derived 2 like protein) is
a transcription factor commonly found in a cell’s
cytoplasm. It activates the transcription of over 500 genes
in the human genome.
Heat exposure activates Nrf2, thereby upregulating a
heat shock protein heme oxygenase-1 (HO-1), which is an
enzyme that breaks down heme (pro-oxidant) to generate
carbon monoxide (anti-inflammatory) and biliverdin and
eventually bilirubin (antioxidant).
This is a desired and protective effect on the body. The
effect of HO-1 upregulation includes inhibition of the
expression of several pro-inflammatory molecules involved
in the pathophysiology of cardiovascular disease.

24. READ MORE ABOUT NRF2 HERE -> https://biohackercenter.com/blogs/biohacking-guides/nrf2-most-important-signaling-pathway-body

25. SAUNA ENHANCES AUTOPHAGY

26. HEALTH BENEFITS OF INFRARED SAUNA / WAON THERAPY
• Reduces oxidative stress in the body
• Speeds up recovery from exercise
• May reduce short- and long-term pain
• May promote the detoxi
fi
cation of the body through increased microcirculation and deep sweating caused by infrared radiation
• May be used as a treatment for chronic fatigue syndrome as it can signi
fi
cantly ease the symptoms (Waon therapy)
• A 2018 meta-analysis showed that exposure to an infrared heat room at 60°C for 15 minutes, followed by a 30
‐
minute rest in a warm
environment,
fi
ve times a week for 2 to 4 weeks, was associated with a signi
fi
cant reduction in B
‐
type natriuretic peptide, cardiothoracic
ratio, and an improvement in left ventricular ejection fraction.

27. NOREPINEPHRINE ↑
DOPAMINE ↑
β-ENDORPHIN ↑
ADRENALINE ↑
4°C
CORTISOL↑
COLD
EXPOSURE

28. ACUTE COLD
EXPOSURE INCREASES
HEART-RATE
VARIABILITY AND
IMPROVES
AUTONOMIC
NERVOUS SYSTEM
ADAPTATION

29. COLD EXPOSURE INCREASES COLD-SHOCK PROTEINS
Cold-Shock Proteins (CSPs) are multifunctional RNA/
DNA binding proteins, characterized by cold-shock
domains (CSDs) that
fi
x misfolded proteins and RNA.
They’re one of the most evolutionarily conserved
proteins found in virtually all organisms.
When cells experience stress related to cold, they
activate cold shock proteins (CSP), which begin to
regulate gene expression.

30. PHYSIOLOGICAL BENEFITS OF COLD EXPOSURE
Cold therapy can decrease in
fl
ammation
Taking an ice bath or a cold shower is great for reducing muscle
soreness or pain and recovery from strenuous exercise (N.b. if your focus
is muscle growth & positive fitness adaptation, wait 2-4 hours after an
intense training session!)
Cold exposure activates the immune system similar to exercise and can
strengthen immunity
A daily hot to cold shower for 30 days resulted in a 29 %
lower self-reported absence from work due to sickness
Immersion in 14 °C water for 1 hour increases metabolic rate by 350 %,
norepinephrine by 530 %, and dopamine by 250 %
Cold exposure increases adiponectin, which is a protein that helps with
blood sugar regulation
Cold exposure activates brown adipose tissue (BAT), which improves
mitochondrial functioning, metabolism, and thermoregulation
All references are found in the free Heat Alteration PDF (see later).

31. AGE-RELATED CHANGES IN BROWN ADIPOSE TISSUE
Ref: Marken Lichtenbelt, W. et al. (2009). Cold-activated brown adipose tissue in
healthy men. New England Journal of Medicine 360 (15): 1500–1508.

32. COLD EXPOSURE & CALORIE RESTRICTION

33. 1-2 minutes
cold exposure @ 0-5°C
in-between
Fast for 16 hours
Exercise for 30 minutes before (optional)
SAUNA 15 MIN @ 80-85°C, REPEAT 3 TIMES
ACTIVATE HEAT & COLD SHOCK
PROTEINS & AUTOPHAGY TO THE MAX

34. 30.03.2023
-12°C

35. COLD SHOWER / HOT SHOWER
ALTERATION
1 minute warm shower
(35–45 °C)
2-5 minute cold shower
(10–15 °C)

36. DOWNLOAD FREE CHAPTER
ON HEAT ALTERATION:
-> biohack.to/heatalteration

37. AUTOPHAGY

38. Cellular self-eating modulates immunity and the elimination of
pathogens via autophagy. The body recognizes damaged cells
and recycles them. Autophagy gets triggered in response to
stress like infections, starvation, high exertion or certain
compounds such as various phytochemicals. You can promote
autophagy with positive stressors such as intermittent fasting,
caloric restriction, regular sauna, exercise and cold exposure.

39. THE AUTOPHAGY PROCESS
Inhibits
Activates

40. THREE MAIN TYPES OF AUTOPHAGY
1. Chaperone-mediated autophagy (CMA): A
selective process where cytosolic proteins bearing a
specific amino acid motif are recognized by
chaperone proteins and delivered to the lysosome
for degradation via a receptor-mediated pathway.
2. Macroautophagy: A bulk degradation process
where cytoplasmic components, including damaged
organelles, are engulfed by a double-membrane
structure called the autophagosome and delivered
to the lysosome for degradation.
3. Microautophagy: A process where lysosomal
membrane invaginates to directly engulf
cytoplasmic components, including proteins and
organelles, for degradation, without forming a
double-membrane structure.
Ref: Ntsapi, C. & Du Toit, A. & Loos, B. (2019). Dietary impact on neuronal autophagy control and brain health. In: Bosch-Bouju,
C. & Layé, S. & Pallet, V. (2019). Feed Your Mind -. How Does Nutrition Modulate Brain Function throughout Life? IntechOpen.

41. AUTOPHAGY REGULATES THE IMMUNE SYSTEM
Ref: Kuballa, P., Nolte, W. M., Castoreno, A. B., & Xavier, R. J. (2012). Autophagy
and the immune system. Annual review of immunology, 30, 611-646.

42. (A) Sirt1 induces the deacetylation, activation, and nuclear translocation of FOXO1.
(B) Sirt1 activation deacetylates and activates FOXO3 transcriptional activity
and subsequent Bnip3-mediated autophagy.
Ref: Kitada, M., Ogura, Y., & Koya, D. (2016). Role of Sirt1 as a Regulator of Autophagy. In Autophagy:
Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging (pp. 89-100). Academic Press.

43. AUTOPHAGY: HEALTH BENEFITS
• May protect from obesity and diabetes
• Autophagy may be involved in the browning of white adipose tissue and
affect the metabolic balance of lipids
• Autophagy helps also prevent NAFLD (non-alcoholic fatty liver disease)
• Better cardiovascular function and protection from cardiovascular diseases
• Impaired autophagy can increase arterial aging
• Protection from oxidative stress and in
fl
ammation
• By eliminating active in
fl
ammasomes
• Elevated liver protection from various liver conditions and diseases
• Improved function of the immune system
• Innate immune receptors and lymphocytes (T and B) are modulated by
autophagy, which represents innate and adaptive immune responses
• Better gastrointestinal function, overall gut health and disease prevention
• Slows down aging and neurodegeneration and may prevent from
neurodegenerative diseases & cognitive decline
• Improves brain plasticity and neuroprotection
• May prevent from certain types of cancers
All references found here: https://biohackercenter.com/blogs/biohacking-guides/autophagy-major-cleaning-system-body

44. LIFESTYLE FACTORS THAT INCREASE AUTOPHAGY
• Intermittent fasting: One of the most effective ways to boost
autophagy. By fasting for extended periods, the body is forced to break
down damaged cells for energy, which can increase autophagy.
• Regular exercise: Exercise has been shown to stimulate autophagy in
the body, especially high-intensity workouts.
• Calorie restriction: Consuming fewer calories than your body needs can
activate autophagy as the body searches for energy sources.
• Ketogenic diet: A diet high in fat and low in carbohydrates has been
shown to activate autophagy in the body.
• Heat alteration: Exposing the body to hot & cold temperatures can
increase autophagy (see earlier).
• Sleep: A lack of sleep can inhibit autophagy – getting adequate rest is
crucial for optimal autophagy function (deep sleep & REM sleep in
particular).
• Reducing stress: Chronic stress can impair autophagy – managing stress
through practices such as meditation, yoga, and deep breathing can
help.

45. NUTRITIONAL FACTORS SUPPORTING AUTOPHAGY
• Sulforaphane -> cruciferous vegetables and broccoli sprouts, in particular.
• Induces autophagy via ERK activation
• Curcumin
• Induces autophagy via the Akt/mTOR pathway
• Coffee -> induces autophagy due to coffee polyphenols
• Caffeine also induces autophagy
• Green tea & EGCG
• Stimulate autophagy in the liver & in the brain
• Ginger
• Induces autophagy by inhibiting Akt/mTOR pathway
• Polyphenols -> in dark & colorful vegetables, berries, leagy greens etc.
• Regulate and induce autophagy & remove aberrant protein aggregates
• Resveratrol -> in dark grapes, berries, cherries & red wine
• Induces autophagy by directly inhibiting mTOR
• Do not take immediately after exercise!
• Extra-virgin olive oil -> contains oleuropein and oleocanthal, polyphenols that
trigger autophagy and inhibit mTOR signaling
• Spermidine -> increases autophagy in the brain and can protect from
neurodegeneration
• External supplementation of spermidine extends lifespan and health span
across species, including in yeast, nematodes,
fl
ies and mice.
All references found here: https://biohackercenter.com/blogs/biohacking-guides/autophagy-major-cleaning-system-body

46. CALORIE
RESTRICTION

47. 1. Multiple studies from over five decades show
that restricting calorie intake (i.e., not eating
excessive amounts of calories) protects from
multiple chronic diseases, improves brain
performance and can protect from memory
diseases.
2. Calorie/caloric restriction (CR) is a dietary
intervention in which you eat fewer calories
than would be typical to your body weight
but ensure that your diet still provides all the
essential nutrients that the body requires for
healthy functioning.
3. Based on animal studies, this would mean 30–
50 % fewer calories compared to normal.
However, for humans, a more appropriate
approach is a 20–30 % calorie restriction to
avoid malnutrition.
4. As little as a 15% calorie restriction has also
improved all health markers (The CALERIE
trial).
Ref: Redman, L. M., Smith, S. R., Burton, J. H., Martin, C. K., Il'yasova, D., & Ravussin, E. (2018).
Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of
living and oxidative damage theories of aging. Cell metabolism, 27(4), 805-815.

50. CALORIE RESTRICTION MIMETICS Depletion of acetyl coenzyme A mimetics:
• Hydroxycitrate
– Garcinia cambogia (sold as a supplement)
– Hibiscus subdariffa (from hibiscus tea)
Inhibitors of acetyl transferases:
• Curcumin
• EGCG (epigallocatechin-3-gallate in green
tea)
• Spermidine (in durian fruit and fermented soy)
• Anacardic acid (in cashew nutshells)
• Garcinol (from the fruit of the kokum tree)
• Gallic acid (in multiple plants such as cacao,
walnuts, flax seed and apples)
Activators of protein deacetylases (mainly
SIRT1):
• Resveratrol (from different plants, berries and
red grape skin) ??? (may not actually activate
SIRT1 - the jury is still out!)
• Quercetin (from different plants, red onion,
kale, red grapes and green tea)
• Piceatannol (from Picea abies [Norway
spruce], passion fruit and red grapes)
• Nicotinamide mononucleotide (NMN
supplement)
• Nicotinamide riboside (NR supplement)
Ref: Madeo, F. & Pietrocola, F. & Eisenberg, T. & Kroemer, G. (2014). Caloric restriction mimetics: towards a
molecular definition. Nature reviews Drug Discovery 13 (10): 727.

51. DO NOT GO TOO LOW IN CALORIES IN THE LONG-TERM
• Lowered basal metabolic rate (BMR) – also called adaptive thermogenesis
• A potential for developing essential nutrient de
fi
ciencies and anemia
• Hormonal depletion, particularly with thyroid hormones and sex hormones
• Decrease in triiodothyronine (T3) and increase in reverse T3 (rT3), which is associated with a reduction in metabolic rate
• Reductions in estrogen and testosterone levels – although in obese men, calorie restriction increases serum testosterone concentrations
due to weight loss
• Greater risk for eating disorders
• Loss of muscle and bone mass (especially after long-term CR) – can persist long after the calorie restriction has been stopped
• Menstrual disturbances, amenorrhea and early menopause
• Low libido and overall energy
• Lowered athletic performance
• Slower healing and tissue growth
• Poorer cognitive functioning
• Mood problems

52. JOIN THE COURSE:
- biohack.to/optimizenutrition

53. WWW.RESILIENT-BEING.COM
THANK YOU!