Debate - Food and Nutraceuticals as Medicine

when does the food become functional

a food with demonstrated physiological benefits and/or reduction of chronic disease risk beyond basic nutrition functions

• features bioactive substances (e.g. lycopene, allicin, sulforaphane)

• does not include fortified foods

• can be consumed as part of a typical diet

• demonstrated health benefits

REMEMBER

food is what is eaten, but food can become functional when consumed by the right person, at the right dose and frequency of consumption to lead to a therapeutic effect

nutraceutical

a substance isolated from food with demonstrated physiological/health benefits and/or reduction of chronic disease risk

• often features bioactive substances (vitamins, minerals, isoflavones, probiotics)

• typically sold in medicinal formats (capsules and tablets)

• often less accessible than functional foods due to cost

drug/pharmaceutical

a substance or mix of substances intended for either:

a) diagnosing, treating, mitigating, or preventing diseases and disorders

b) restoring, correcting, or modifying organic functions

c) disinfection of premises in which food is manufactured, prepared or kept

• over the counter or prescribed

• administered in a large variety of formats

• heavily regulated: - food and drugs acts, controlled drug and substances act, patented medicines regulations

functional foods formats

natural food form, low processing

nutraceuticals forms

pills, liquids, capsules, powder

medicine forms

pills, liquids, capsules, tablets, topical, inhalers, injections, etc

bad diet effect on diabetes

diets high in sugars, carbs, and unhealthy fats: insulin resistance and metabolic dysfunction

good diet effect on diabetes

diet rich in whole grains, lean proteins, fiber, and heathy fats, physical inactivity: prevent, manage, or even reverse early stages diabetes

example of medication, nutraceutical, and functional food that may benefit blood glucose levels

medication: Metformin

nutraceutical: Berberine

functional food: Cinnamon

what does long term exposure to high glucose levels lead to

permanent damage to the eyes, kidneys, nerves and blood vessels. it also significantly increases the risk of CVD

case study CV

35yo female

diagnosed with T1DM at 21

eating disorder history: withholding insulin; attempted to manage T1DM through diet alone

→ chronic uncontrolled blood glucose levels (HbA1C > 10%)

case study LG

LG is a 57 yo male

diagnosed with T2DM at age 55

family history of CVD

LDL-c elevated: 4.2mmol/L (on a statin)

HbA1C elevated: 7.1%

hesitant to start metformin (medication) - refused

motivated to change diet and physical activity

berberine origin and study

berberine is extracted from coptis root and phellodendron chinese herbs

a meta-analysis included studies where individuals with T2DM consumed 0.6g-2.7g of berberine for 56-112 days

when was berberine effective in reducing blood glucose

when taken in combination with oral hypoglycemics vs. taking oral hypoglycemics alone

• fasting plasma glucose: -0.67 mmol/L

• postprandial glucose: -0.98mmol/L

• HbA1C: -0.58%

berberine vs. oral hypoglycemics

• there were no statistically significant effect differences in blood glucose changes

• i.e. they were equally effective

side effects of berberine

• increased risk of side effects with increased berberine dose

• incidence of adverse reactions was low, and side effects were relatively low risk: nausea, diarrhea, constipation (note: similar side effects with metformin, especially when first starting the medication)

cinnamon

• obtained from the inner bark of the cinnamon tree

• it has been reported to possess antimicrobial, anti-inflammatory, antioxidant, antifungal, and antidiabetic properties

main bioactive components in cinnamon

cinnamaldehyde

cinnamic acid

cinnamate

as well as many polyphenols

meta analysis of cinnamon

meta-analysis: participants consumed 1-6g/day of cinnamon or 0.12-0.5g/day of cinnamon extract for a duration of 40-120 days

cinnamon effect on fasting plasma glucose

• cinnamon was found to decrease fasting blood glucose by 19mg.dL (1.03 mmol/L)

• no effect on HbA1C and serum insulin (consider the timeframe of 40-120 days; we need about 90 days to see a change in HbA1C)

metformin

commonly prescribed for the prevention/treatment of type 2 diabetes (improves insulin sensitivity, decreases intestinal absorption of glucose)

it has demonstrated to be a long-term tool for diabetes prevention in patients with prediabbetes

Meta-analysis: trial duration from 8-156 weeks and dose of metformin from 1000 to 3000 mg/d

metformin effect on blood glucose

• HbA1C reduced by 1.05% vs. placebo

• fasting blood glucose reduced by 0.47 mmol/L vs. placebo

result of CM case study → attempted to manage T1DM through diet alone

→ kidney transplant in 2018, long-term nerve and ocular damage

result of case study LG → hesitant to start metformin - motivated to change diet and physical activity

→ AIC: 6.3% (within target for T2DM)

hypertension

>135/>85 mm Hg

a condition that

• affects the blood vessels of the bdoy

• results in consistently high force and pressure of blood pushing against vessel walls - can cause damage that can reuslt in atherosclerosis

• causes the heart to work harder to pump blood

• is the leading risk factor for CVD - can lead to heart attack and heart failure so it is very important to manage

• can be a result of too much sodium in diet

• known as the silent killer

medication, nutraceutical, functional food for hypertension

medication: ACE inhibitors (Enalapril, lisinopril)

nutraceutical: magnesium

functional food: garlic (raw)

magnesium and hypertension

• inadequate consumption of certain minerals, including magnesium is a risk factor for hypertension

• magnesium acts as a calcium antagonist on smooth muscle, resulting in vasorelaxation

• a 2012 meta-analysis of 22 trials found an overall significant decrease of (systolic BP, diastolic BP)

effect of magnesium supplementation on BP

blood pressure decrease was statistically significant but small elemental magnesium supplement dose: 120-973 mg (mean: 410mg)

garlic and hypertension

used in the management of a variety of health conditions for thousands of years

exerts antihypertensive effects biochemically:

• inhibits angiotensin-converting enzyme activity

• reduces synthesis of vasoconstricting prostanoids

• enhances nitric oxide (NO) activity

Many of these benefits are exerted by the bioactive component allicin

garlic and hypertension studies show

a systematic review and meta analysis found garlic to have significant effects on systolic and diastolic blood pressure

overall significant decrease of:

• systolic blood pressure: -6.71 mm Hg

• diastolic blood pressure: -4.8mm Hg

• also found garlic to be safe

• limitations: lack of long-term studies and RCTs demonstrated risk of bias

ace inhibitors and hypertension

angiotensin-converting enzyme (ACE) inhibitors target the renin-angiotensin-aldosterone system (RAAS)

• overactive RAAS associated with higher bloo dpressure

ACE inhibitors also characterized by decrease in the bradykinin degradation- leads to a release of NO and prostaglandins, therefore causing vasodilation

ACE inhibitors shown to significantly decrease all-cause mortality in hypertensive patients

chronic inflammation

a long-term inflammatory state in which there is an increased production of pro-inflammatory mediators such as cytokines and adhesion molecules

chronic inflammation supports the development of Noncommunicable diseases (NCDs) - cardiovascular disease, cancer, chronic respiratory disease and diabetes

medication, nutraceutical, functional food example for chronic inflammation

medication: NSAIDS (ibuprofen, COX2 inhibitors)

nutraceuticals: curcumin

functional food: nuts

what is curcumin

a bioactive polyphenol most potently found in tumeric

meta analysis of curcumin

trial duration ranged from 12 days to 24 weeks.

curcumin dosage ranged from 46-4275mg/day

curcumin reduced TNF-a, MCP-1, IL-8. IL-6, and CRP compared to control, and increased IL-10 compared to control

curcumin was more effective at lowering CRP concentrations as the duration of consumption increased (overall CRP change: -1.55mg/L)

was the meta analysis on curcumin accurate

however, the risk of bias in the studies included in this meta-analysis was highly variable

the greatest lowering effects on CRP was found in the negative-quality studies, followed by the neutral-quality studies and lastly the positive-quality studies

this trend was also seen with the findings for IL-6 and TNF-a

Nuts and inflammation

a meta-analysis evaluated the impact of a variety of nuts, such as walnuts, almonds, pistachios, peanuts, hazelnuts, cashews, and mixed nuts

intervention duration: 4 to 48 weeks

dosage of nut consumption from 28-128g/day

what did nut consumption do

nut consumption reduced ICAM-1 levels, specifically in mixed nuts

across all nuts, there was no significant effect on levels of CRP, VCAM-1, TNF-a, IL-6, and E-selectin

NSAIDs

non-steroidal anti-inflammatory drugs are typically used to reduce pain and inflammation

however, not all NSAIDs are considered equal

meta-analysis on NSAIDs

• meta-analysis of RCTs in patients with rheumatoid arthritis

• included 19 RCTs of 1- different NSAIDs

• overall: no effect on CRP

• Naproxen: significant reduction in CRP (SMD: 0.11)

• NSAID side effects: stomach ulcers, stomach pain, nausea, headaches, dizziness, kidney damage, etc

how does misinformation in the media contribute to perceptions about food/nutraceuticals as medicine

functional foods and nutraceuticals:

• lack of regulatory compliance oversight (esp. nutraceuticals) - presence of other compounds not listen on the label

• lack of experimental evidence

• false advertising

• contamination with heavy metals

• interactions between supplements/nutrients/herbs and drugs?

• potentially pushes the misunderstanding of “more is better” - this may lead to the consumption of excess nutrients, leading to toxicity

problems on all ends

medicine

• adverse drug reactions

• high potency

• inappropriate dosage for certain (complex) patients

• inappropriate prescription

• failure of drug knowledge

• drug-drug interactions (many unknown)

is food medicine? are nutraceuticals medicine?

• inspiring message, or guilt inducing message (guilt that you caused your disease by not eating properly)

• consider effect sizes with medication vs. FFN

• consider the role of nutrition in disease prevention

• how are FFN perceived when it comes to their impact on health? how about medication?

• consider statistical significance vs. clinically meaningful results

• are the forms of FFN similar or different to medication?