Food is unpalatable without herbs and spices. Recent discoveries of ion channels as the final pathway for pain perception and their blockade by phytochemicals from herbs and spices opens a new era for the topical treatment of painful conditions in man.

1. SCIENTIFIC BASIS
OF
FOOD AS MEDICINE
By
Kevin KF Ng, MD, PhD.
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, FL., USA
Presented at Traditional and Integrative Medicine Webinar
July 14th, 2023
Email:kevinng68@gmail.com

2. Lecture Outline
▪ Results of a Poll on the belief of Food as
Medicine
▪ Use of botanical products by Hippocrates
▪ Discovery of how aspirin works by JR Vane
▪ Teaching and research in Singapore and the
United States
▪ Personal Research into Food as Medicine,
inflammation and pain perception.
▪ Strategy to alleviate pain and suffering with
phytochemicals acting on TRP ion channels.
▪ Summary
https://www.dole.com/en/blog/healthy-living/food_is_medicine

3. How true is Hippocrates’ teaching after more than 2,000 years that
Food is Medicine
The 1-week poll results from LinkedIn.net Sept. 2021
©DRKEVINKFNG

4. Number of publications on “Food as Medicine” in PubMed
from 1808 to 2022
https://pubmed.ncbi.nlm.nih.gov/?term=food%20as%20medicine&timeline=expanded
1980

5. Hippocrates (460-370 BC): Father of
Western Medicine

6. Some botanical products used by Hippocrates (460-370 BC)
Sources: Internet

7. Hippocrates used bark of white willow tree for several symptoms
▪ Hippocrates used it for:
▪ Fever
▪ Headache
▪ Toothache
▪ Arthritis
▪ Menstrual craps
▪ White willow bark is now known to contain
salicylic acids and flavonoids

8. Aspirin from empirical use to rational treatment
takes 2,144 years
~2,000 years
60 years
74 years
©DRKEVINKFNG

9. Institute of Basic Medical Sciences
Royal College of Surgeons England
University of London
https://www.bing.com/images JR Vane, 1982 Nobel laureate

10. Assay of vasoactive hormones in circulating blood
©DRKEVINKFNG

11. Discovery of lung angiotensin converting enzyme
(ACE) and ACE inhibitor in 1967

12. Discovery of angiotensin converting enzyme (ACE)
in the lung (1967)
©DRKEVINKFNG

13. Fate of chemical mediators of inflammation during
passage through the lungs
Conversion of angiotensin I to angiotensin II
In pulmonary circulation
Angiotensin II

14. Illustration of an organ bath using guineas pig ileum

15. Inhibition of cyclooxygenase activity in homogenate of guinea
pig lung by nonsteroidal anti-inflammatory drugs (1971)
% inhibition

16. Faculty of Medicine, University of Singapore

17. Miller School of Medicine, University of Miami
Division of Clinical Pharmacology
• 1981 to 2005
• Clinical medicine
• 150 clinical trials
• 2005 to present
• Food as Medicine
• Food Nutrients
• Phytochemicals
• Pain mechanism

18. FOOD AS MEDICINE
SOLUTION FOR
CHRONIC INFLAMMATION

19. What is Food?
Nutrients
Essential
Nutrients
Non-Essential
Nutrients
Phytochemicals
• Amino acids (9)
• Vitamins (13)
• Minerals (15)
• Fatty acids (2)
• Dietary fiber
• Carbohydrates
• Proteins
• Fats
• Water
Food

20. Nutritional classification of foods
Nutrients
Essential
Nutrients
Non-Essential
Nutrients
Phytochemicals
• Amino acids (9)
• Vitamins (13)
• Minerals (15)
• Fatty acids (2)
• Dietary fiber
• Carbohydrates
• Proteins
• Fats
• Water
Food

21. Nutritional classification of foods
Nutrients
Essential
Nutrients
Non-Essential
Nutrients
Phytochemicals
• Amino acids (9)
• Vitamins (13)
• Minerals (15)
• Fatty acids (2)
• Dietary fiber
• Carbohydrates
• Proteins
• Fats
• Water
Food
2,000 Cal Diet 97% 3%

22. PHYTOCHEMICALS

23. What are phytochemicals?
▪ “Phyto” is a Greek name for plants.
▪ “Chemicals” are compounds that
occur naturally in plants.
▪ There are about 5,000 phytochemicals.
▪ Only 150 have been studied in depth.
https://www.breastcancer.org/tips/nutrition/reduce_risk/foods/phytochem

24. General classification of phytochemicals
There are > 5,000 phytochemicals
Salicylic acid
gingerol piperine
Terpenoids
menthol
Polyphenolic
curcumin

25. Functions of phytochemicals in humans
▪ Phytochemicals have not been shown to be essential nutrients.
▪ However, they have been shown to be beneficial for health by:
▪ Scavenging free radicals. ▪ Lowering high blood pressure
▪ Reducing inflammatory response ▪ Lowering high blood sugar
▪ Modulating cytokine release ▪ Lowering high blood cholesterol
▪ Reducing the risk of cancer ▪ Lowering the risk of obesity
▪ Preventing telomeres from shortening ▪ Lowering the risk of degenerative
diseases
▪ The discovery of ion channel TRPA1 in 2005 as a final pathway for
pain perception and its blockade by phytochemicals opens a new
era for pain research.

26. ION CHANNELS

27. What are ion channels
https://www.nature.com/scitable/topicpage/ion-channel-14047658/
Plasma membrane
cytoplasm
Ion channels are pores in the cellular membrane that allow the
passage of ions across the impermeant lipid cell membrane.

28. Classification of ion channels
https://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=78
• 300 different ion channels
• 13 superfamilies
• 6 TRP subfamilies
• Only TRPV1 and TRPA1 are
widely studied for pain, cold,
and itch
6 TRP subfamilies (27 ion channels)
Pain
Pain
7
8
1
3
3
5

29. Transient receptor potential channels
https://www.wikiwand.com/en/Transient_receptor_potential_channel
https://www.frontiersin.org/articles/10.3389/fnins.2020.00782/full

30. The Functions of TRPA1 ion channel (2022)
▪ TRPA1 is an ion channel located on the plasma membrane
of many human and animal cells.
▪ It is a sensor for pain, cold, itch, and environmental
irritants.
▪ TRPA1 is activated by a number of
▪ reactive compounds:
▪ allyl isothiocyanate, cinnamaldehyde, farnesyl thiosalicylic acid,
formalin, hydrogen peroxide, 4-hydroxynonenal, acrolein, and tear
gases
▪ and non-reactive compounds (nicotine, PF-4840154[16]) and is thus
considered as a "chemosensor" in the body.
▪ TRPA1 is co-expressed with TRPV1 on nociceptive primary
afferent C-fibers in humans.
▪ TRPA1 is considered the final pathway for pain perception
and a target for intense research
▪ The discoveries of TRPV1, TRPA1, TRPM8 an others led to
the award of Nobel Prize to D. Julius and A. Patapoutian
https://www.news-medical.net/health/Types-of-Ion-Channels-in-the-Body.aspx

31. Synthetic and natural TRPA1 antagonists
TRPA1 antagonists Natural TRPV1 & TRPA1
synthesized by antagonists

32. Extraction of phytochemicals and
clinical tests
Materials
• Vegetables
• Fruits
• Herbs
• spices
Solvents
• Water
• Alcohol
• Carrier oils
Product
• Tincture
• Liniment

33. INFLAMMATORY PAIN

34. Natural history of fire ant sting

35. Effect of Phytochemical Extracts
(chili pepper, ginger, lemongrass, and aloe)
on Fire Ant Stings
Untreated for 36 hours Treated for 36 hours

36. Effect of black pepper extract on yellow jacket sting on lip:
my personal experience
2.43 PM Jul 29 2019
4.08 PM Jul 28 2019
Before After

37. NOCICEPTIVE PAIN

38. Effect of black pepper extract on acute injury
brick wall abrasion
site of fall

39. Effect of phytochemical extracts (ginger, chili pepper,
lemongrass, and aloe) on muscle soreness

40. 74 yr old Chinese female twisted her right ankle while going
down the staircase. She was unable to stand up because of the
severe pain. Physical examination showed a tender bruised
right ankle with a limited range of movement. Topical
application of oil extracts containing four ingredients were
applied three times a day followed by immobilization with an
ankle brace. The pain was reduced from10/10 to 2/10 within
15 minutes. She became pain-free after 1 day and ambulatory
after 2 days.
Effect of phytochemical extracts
(chili pepper, ginger, lemon grass, aloe)
on Sprained Right Ankle

41. Effect of black pepper extract on
post-laparotomy cholecystectomy pain

42. 61 yr old Chinese male with 12 yr history
of type 2 Diabetes. VPT? Complained of
Numbness, pain, and swelling in both
legs. Meds: metformin 850 mg 3 times
daily, nifedipine 10 mg daily, Vit B
complex.
Physical Examinations showed mycotic
nails, subnormal pedal pulse, and
diminished sensation in both legs
Topical treatment with L35 reduced
numbness, pain, and swelling from 100%
to less than 5% within 10 to 60 minutes.
The relief lasted about 4 hours. Three
applications a day produced complete
relief in 1 week.
Effect of phytochemical extracts
(chili pepper, ginger, lemongrass, aloe, and limonene)
on painful diabetic neuropathy
Before
After

43. MECHANISM OF PAIN RELIEF
BY
BLOCKING TRPA1 ION CHANNEL

44. Pain Perception and Dermal Nerve Plexus of
Human Skin
https://www.sciencedirect.com/scienc
e/article/pii/S0022202X15305935#f
0015
Gene Therapy for Chronic Pain Management
http://dx.doi.org/10.5772/5505

45. Functional Anatomy of Nociceptors and Afferent Fibers (2010)
https://www.researchgate.net/publication/265425188_Functional_Anatomy_of_Muscle_Muscle_Nociceptors_and_Afferent_Fibers

46. This is how a nerve ending looks.
It has been broken open to reveal vesicles (orange and blue) containing chemicals used
to pass messages in the nervous system (2020)
Principles of Neural Science (Principles of Neural Science (Kandel)) 5th Edition

47. Proximity of afferent sensory nerve endings to blood vessels:
Neurogenic pain perception
https://www.researchgate.net/figure/9-Events-occurring-around-a-muscle-
nociceptor-during-noxious-mechanical-stimulation-The_fig4_265425188

48. Antidromic axon reflexes induce the release of neuropeptides:
Inflammatory pain perception(2012)
https://www.researchgate.net/figure/Neuronal-factors-released-from-nociceptor-sensory-neurons-directly-drive-leukocyte_fig4_230573679
SP
CGRP
1. Neurogenic
inflammation
2. Vasodilation
4. Pain sensation
3. Immune-
mediated
inflammation

49. Chemical mediators of inflammation released by
trauma, infection and chemicals
Stimuli
• Injury
• Infection
• Chemical
Source
• Tissue cells
• Immune cells
• Endothelium
• Nerves
• Fibroblasts
• Plasma
Mediators
• Histamine
• Serotonin
• Prostaglandins
• Leukotrienes
• Platelet activating
factor
• Nitric oxide
• Bradykinin
• Cytokines
• Chemokines
• Neuropeptides
• SP
• CGRP
©DRKKFNG

50. Substance P (SP) and Calcitonin gene-related peptide (CGRP)
▪ Substance P (SP):
▪ It is primarily released by sensory nerve fibers
▪ It is released in response to inflammation, tissue
injury, and nerve stimulation.
▪ It is involved in neurogenic inflammation, where it
contributes to vasodilation, plasma extravasation,
and the recruitment of immune cells to the site of
inflammation.
▪ It is generally regarded as a "universal" mediator
of inflammation.
▪ Calcitonin gene-related peptide (CGRP):
▪ It is released by sensory nerves as well as other
cell types, such as mast cells, macrophages, and
endothelial cells.
▪ Its release is also stimulated by inflammation,
nerve stimulation, and certain cytokines.
▪ CGRP is involved in vasodilation, modulation of
immune responses, and sensory neuron
sensitization.
▪ Its elevated blood levels in migraine headaches
led to the development of antibodies and
antagonists for the treatment of migraine.
11 amino acids;
Molecular weight 1347.63
Molecular Weight of pro-CGRP/active form: 13 kDa/5 kDa
Molecular Weight of CGRP active form: 5 kDa
35 amino acids.

51. Pain perception induced by mediators from
intense exercise, infection, and chemicals
PAIN
©DRKKFNG

52. The current strategy to treat somatic pain:
anti-inflammatory drugs
PAIN
• Aspirin blocks the generation of prostaglandins
• Diphenhydramine blocks the action of histamine
• Many other inflammatory mediators are unopposed ©DRKKFNG
• Steroids
• Antihistamine,
• Aspirin, NSAIDs

53. The potential strategy to treat somatic pain:
synthetic TRPA1 antagonists?
PAIN
• Aspirin blocks the generation of prostaglandins
• Diphenhydramine blocks the action of histamine
• Many other inflammatory mediators are unopposed ©DRKKFNG
28 Synthetic TRPA1 antagonists

54. Looking ahead to the future of
Topical Pain Management:
PAIN
×
Inhibition of activation of ion channels renders a wide-spectrum blockade
©DRKKFNG
Phytochemical TRPA1 antagonists
×

55. List of Some Natural TRPV1 and TRPA1
Pain Blockers/Antagonists
×
©DRKKFNG

56. Overall effects of phytochemical extracts on pain perception
in various painful conditions
▪ Nociceptive pain:
▪ Soft tissue injuries
▪ Post-surgical pain
▪ Radiation dermatitis
▪ Low back pain
▪ Stiff neck
▪ Inflammatory pain:
▪ Fire ant stings
▪ Wasp stings
▪ Yellow jacket stings
▪ Mosquito bites
▪ Medical conditions
▪ Itch in psoriasis
▪ Arthritis pain
▪ Diabetic neuropathy
▪ Gouty arthritis
▪ Migraine headache
▪ Menstrual cramp
▪ Pregnancy back pain
Arbitrary pain scale 0-10 (no pain to extreme pain)
Before treatment After treatment
8-10 0-2
©DRKKFNG

57. Poll results on 5/17/2023 on the preference for
Topical TRP Pain Blocker on LinkedIn
https://www.linkedin.com/company/11772752/admin/

58. Summary
▪ Hippocrates advocated Food as Medicine more than 2,000 years ago.
▪ It is now known that food contains nutrients that are essential for health.
▪ The essential nutrients include macronutrients (carbohydrates, proteins,
and fats) and micronutrients (vitamins, and minerals). Added to the list
are essential fatty acids, and dietary fibers.
▪ Phytochemicals, which make up 3% of a 2,000 Cal diet are derived from
plants that show antioxidant, anti-inflammatory, immuno-modulatory,
and anti-cancer properties.
▪ Herbs and spices contain phytochemicals that modulate pain perception
by blocking the activation of nociceptive receptors TRPV1 and TRPA1 ion
channels.
▪ The actions of phytochemicals on sensory TRP channels open a new era
for the topical treatment of pain.

59. Thank you
Q and A time
https://www.slideshare.net/ssusera9ba27