15. ORTHOMOLECULAR Flashcards
This module covers:• The dietary sources, bioavailability and interactions of orthomolecular compounds and medicinal mushrooms.• The therapeutic uses and safety considerations.• Appropriate dosage levels and preferred forms for orthomolecular compounds and medicinal mushrooms.
What nutrient is reduced by the statin group of pharmaceutical drugs and why does this happen?
CoQ10.
Statins are drugs used to reduce cholesterol synthesis through the inhibition of (HMG CoA reductase and) the Mevalonate Pathway. But they also reduce CoQ10 because both compounds are synthesised via this metabolic pathway.
Slide 12-13
Why is Alpha Lipoic Acid so effective as an antioxidant?
- ALA is referred to as ‘universal antioxidant’ since it functions in a fat-soluble and water-soluble environment. Exogenous forms scavenge free radicals intra- and extra-cellularly.
- Furthermore it can regenerate other antioxidants such as vitamin E, C, glutathione and CoQ10. It also up-regulates the expression of glutathione.
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What are THREE key ways that chondroitin
protects cartilage?
Chondroitin protects cartilage from degradation by:
- Reducing degradative enzymes.
- Decreasing inflammation — reduces inflammatory intermediates such as COX-2. This is also seen by reductions in the inflammatory marker ‘CRP’.
- Increasing hyaluronic acid synthesis, thereby enhancing joint lubrication.
Outline TWO ways that N-acetyl glucosamine can be of benefit for IBD.
- NAG supports the GI epithelial barrier by enhancing mucin functionality, which is dramatically altered in those with IBD. Mucins are a group of proteins found in mucus that form a barrier and prevent microbial overgrowth.
- NAG also reduces biofilm formation associated with IBD.
Briefly explain why betaine (TMG) can reduce the risk of cardiovascular disease.
TMG serves as a methyl donor, facilitating the conversion of homocysteine to methionine.
(Elevated homocysteine is a risk factor for CVD, so betaine can be used therapeutically to support vascular endothelial health and prevent atherosclerosis.)
Outline TWO ways in which phosphatidylserine is beneficial for Alzheimer’s disease.
- Phosphatidylserine reduces hippocampal inflammation.
- It also reduces acetylcholinesterase thereby increasing the availability of the neurotransmitter acetylcholine which is vital for memory and information processing.
Other options:
- Increases other neurotransmitters such as noradrenaline, serotonin and dopamine.
- It has been found to preserve glucose metabolism during Alzheimer’s disease.
- Increases cognitive function (including non- Alzheimer’s related cognitive decline) and memory
Who coined the term ‘orthomolecular’?
What are orthomolecular compounds?
Give two examples
Linus Pauling coined the term ‘orthomolecular’ in the 1960s to mean “the right molecules in the right
amounts” (ortho- in Greek implies ‘correct’).
- Orthomolecular compounds are highly beneficial for health, and although they are naturally synthesised by the body, additional amounts can be sourced from the diet or from supplementation.
- These compounds do not fit into the category of other nutrients such as vitamins or minerals.
- Examples of orthomolecular compounds include: CoQ10, alpha-lipoic acid, glucosamine and chondroitin sulphate.
What is accelerated aging caused by?
How might you slow it down or reverse it using orthomolecular therapy?
What else might you consider?
The ageing process is typically accelerated as a result of free radical exposure, chronic inflammation and toxic exposure.
- Reversing or slowing it down is one goal of orthomolecular therapy.
This might involve using CoQ10, ALA or antioxidants. - Be sure to address an individual’s overall diet and lifestyle with the guidance of core naturopathic nutrition principles. Supplements alone will not single-handedly support healthy ageing.
Where can Coenzyme Q10 be found in the human body?
What role does it play?
What form does it exist in?
What reduces CoQ10?
Coenzyme Q10 (CoQ10) is present in each cell’s mitochondria and plays a key role in ATP production.
- CoQ10 is also known as ubiquinone.
- It exists in the body in an oxidised form (ubiquinone) and a reduced form (ubiquinol) and the two forms interconvert.
- It is usually synthesised in the body in sufficient amounts to meet physiological requirements.
- CoQ10 is reduced by: Ageing, drugs (e.g. statins), smoking and certain diseases (e.g. cardiovascular disease).
Name 3 plant sources of CoQ10
Name 3 animal sources of CoQ10
How much CoQ10 is lost if food is fried?
Dietary intake contributes around 3 to 6 mg per day.
Food sources:
- Plant sources: Nuts (e.g. peanuts, pistachios), sesame seeds, olive oil, fruit and vegetables including oranges, strawberries, avocado, broccoli, cauliflower,
- Animal sources: Meat, poultry, fish (e.g. herring, sardines, mackerel, trout) and eggs
Approx. 14%‒32% of CoQ10 is lost if foods are fried.
Why is CoQ10 useful in energy production?
- CoQ10 is needed for the electron transport chain (for complex 2 of 4 in this process) — review biochemistry.
This supports mitochondrial function and energy production. - The highest quantities are found in muscle cells (including skeletal and cardiac muscle) due to the high ATP demand for muscle contraction.
- Therapeutic uses: Fatigue, Fibromyalgia. Daily use (300 mg in divided doses; i.e. 3 x 100
List 3 ways that CoQ10 is useful as an antioxidant and give one therapeutic use for CoQ10 as an antioxidant.
- CoQ10 is a potent fat-soluble antioxidant that inhibits the peroxidation of cell membrane lipids. It neutralises free radicals produced by mitochondria.
- CoQ10 naturally decreases with age; the ageing process involves ROS and impaired mitochondrial function.
- Depletion of CoQ10 can result in mitochondrial dysfunction, which is associated with conditions including fibromyalgia, Type 2 diabetes, CVD, neurodegenerative diseases and cancer.
Therapeutic Uses:
* Healthy ageing: 100–200 mg per day.
* Preventative measures or for directly addressing mitochondrial dysfunction (e.g. fibromyalgia etc.)
Name a ways that CoQ10 is useful for periodontal health
Name a therapeutic use for CoQ10 in periodontal health
Periodontal health
* Diseased gum tissues have significantly lower levels of CoQ10 in comparison with healthy gum tissue. This is thought to be a result of the lipopolysaccharides from the bacteria Porphyromonas gingivalis, triggering oxidative stress and mitochondrial dysfunction.
Therapeutic Uses:
* Periodontitis. Daily 50–80 mg
* Combine with periodontal care routine.
Name 2 ways that CoQ10 is useful for male & female fertility
What would a therapeutic dose of CoQ10 be for male & female fertility?
Male fertility
* CoQ10 protects sperm from oxidative stress (to which they are vulnerable).
* 200–300 mg for 6 months increases sperm health.
Female fertility
* Impaired mitochondrial performance (low CoQ10) can drive age-associated oocyte (egg cell) deficits and lead to infertility.
* 100–600 mg for ovarian health.
Name 3 ways that CoQ10 is useful for cardiovascular health
What would a therapeutic dose of CoQ10 be for cardiovascular health?
Cardiovascular health
* Crucial for cardiac muscle function.
* Protects against endothelial dysfunction and hence atherosclerosis.
* CoQ10 reduces LDL oxidation.
* It inhibits the NF-kB activation that is secondary to ROS.
* Increases superoxide dismutase activity (an anti-oxidant) which is known to preserve the activity of nitric oxide (NO) as a potent vasodilator.
* Hypertension, angina pectoris, congestive heart failure, post myocardial infarction.
- Typical dosage: 60–300 mg / day.
NF-κB = a protein that controls inflammatory cytokine production
How do statins and CoQ10 interact?
What are the risks of low CoQ10 levels?
Statins and CoQ10:
* Statins are drugs used to reduce cholesterol synthesis but they also reduce CoQ10 because both compounds are synthesised via the same pathway.
* Cholesterol and CoQ10 have vital functions in the body and their loss contributes to the adverse effects caused by statins.
- Low CoQ10 levels increase the risk of various illnesses including cardiovascular disease, myopathy and depression.
- 90–300 mg / day of CoQ10 greatly reduces this risk
Describe the Mevalonate Pathway.
The Mevalonate Pathway:
* This metabolic pathway is required for the production of cholesterol and CoQ10 — two crucial molecules for health.
* Statins act on this pathway
Acetyl-CoA → HMG-CoA → (HMG-CoA reductase inserts here & is inhibited by statins) → Mevalonic acid → Cholesterol OR → CoQ10
(Check slide 13 for image)
There is a debate about which is better, ubiquinol or ubiquinone, describe.
It is suggested that ubiquinol is a better supplemental form for CoQ10 status enhancement than ubiquinone. However:
* Results are mixed with very little research supporting this claim.
* Bioavailability is influenced more by the composition of the raw material, which for supplemental purposes is generally synthesised using a yeast-fermentation method.
* This produces a crystalline form which is difficult to digest.
* The crystals needs to be dissociated into individual CoQ10 molecules and remain in the shelf-life of the product.
* Thus solubilised products appear to have the greatest bioavailability.
What is the safety profile of supplementing with CoQ10?
What are the adverse effects of supplementing with CoQ10?
Are there any drug interactions with CoQ10?
Supplementation:
* Safety: CoQ10 has a remarkable safety profile. There have been no reports of significant adverse side effects of oral CoQ10 supplementation at doses as high as 1200 mg / day for up to 16 months. There have been no safety studies in pregnant and lactating women.
- Mild adverse effects: GIT symptoms such as nausea, diarrhoea, appetite suppression, heartburn, and abdominal discomfort have been reported. These may be minimised if daily doses higher than 100 mg are divided into two or three doses.
- Interactions: CoQ10 may decrease the effects of warfarin.
What is Alpha lipoic acid (ALA)?
How is it also known?
Do humans synthesise enough alpha lipoic acid to meet basic needs?
Alpha lipoic acid (ALA) is an organosulphur compound that is synthesised by plants and animals, including humans. ALA is a naturally-occurring, short-chain fatty acid.
- ALA is also known as ‘α-lipoic acid’ or ‘lipoic acid’ (LA).
- There are two forms of ALA: R-form (natural) and S-form (synthetic). The R-ALA variant is nearly 10 x more potent.
- It is thought that humans generally synthesise enough to meet basic needs.
- However, additional ALA in the form of supplementation has clear therapeutic benefits in certain health conditions.
Name 2 plant sources of Alpha lipoic acid (ALA)
Name 2 animal sources of Alpha lipoic acid (ALA)
Food sources:
* Found in a wide variety of foods.
* Plant sources: Brassicas (e.g. broccoli, Brussel sprouts), spinach, potato, carrots, beets, tomatoes, peas, brewer’s yeast.
* Animal sources: Red meat (lamb, beef) and organ meats.
Which characteristics of Alpha Lipoic acid (ALA) has earned it the the title of ‘universal antioxidant’?
Give 2 therapeutic uses for ALA as an antioxidant.
- ALA is a potent antioxidant that can be produced within the body and functions in both a fat-soluble and water soluble environment. It is anti-inflammatory.
- Exogenous forms (from food and supplements) scavenge free radicals intra- and extra-cellularly.
- It can regenerate other antioxidants such as vitamin E, C, glutathione and CoQ10. It also up-regulates the expression of glutathione.
- Improves the motility of spermatozoa and provides antioxidant protection
Therapeutic uses:
* Infertility (600 mg daily)
* Diabetes, diabetic neuropathy
* Alzheimer’s disease — slows the cognitive decline (600 mg daily for one+ year).
* Multiple sclerosis.
* Healthy ageing.
Why would Alpha lipoic acid (ALA) be useful for a client with diabetes?
ALA supplementation improves insulin sensitivity, insulin resistance, fasting blood glucose and HbA1c which are all markers of diabetes severity. Diabetes mellitus: 300–1200 mg per day.
How is Alpha lipoic acid (ALA) useful for metal chelating
In which pathologies would this be useful?
ALA can chelate iron, mercury, copper, lead and zinc.
Therapeutic uses:
* Infertility.
* Alzheimer’s.
* Peripheral neuropathy.
How is Alpha lipoic acid (ALA) useful for peripheral neuropathy?
- ALA supplementation reduces oxidation of the myelin sheath.
- ALA improves neuropathic sensory symptoms including pain, burning, numbness, prickling of the feet and legs.
- Dosage: 600 mg per day.
How is Alpha lipoic acid (ALA) useful for weight loss?
ALA is thought to promote weight loss via various mechanisms:
* Reducing the oxidative stress that promotes fat storage.
* Suppressing appetite and hence food intake through its influence on the enzyme ‘AMPK’ (AMP-activated protein
kinase) in the hypothalamus (where appetite is regulated).
* Increasing energy expenditure and reducing fat synthesis.
* Dosage: 1800 mg daily.
When supplementing with Alpha lipoic acid (ALA) how should supplements be taken?
Are there any adverse effects to be aware of?
What are the drug interactions with ALA?
Supplementation:
* Supplements should be taken on an empty stomach to optimise bioavailability, i.e. one hour before, or two hours after food.
- Rare adverse effects: Allergic reactions affecting the skin (rashes, hives) and GI symptoms (abdominal pain, diarrhoea).
Interactions:
- Biotin and ALA may compete for transport across cell membranes due to similar chemical structures.
Be mindful of biotin deficiency when using high doses of ALA.
- Increased risk of hypoglycaemia in medicated diabetic patients due to additive effect. Monitor blood glucose closely.
What is glucosamine?
Where is glucosamine found in high concentrations in the human body?
Glucosamine is an amino sugar naturally present in most body tissues, with high concentrations in joints and cartilage.
* Glucosamine is required for the synthesis of glycoproteins, glycolipids, and glycosaminoglycans (GAGs), also known as mucopolysaccharides.
* These compounds are an important structural component of tendons, ligaments, cartilage, synovial fluid, mucous membranes and structures in the eye, blood vessels and heart valves.
Name 2 supplemental forms of glucosamine
Glucosamine can be supplemented in two different forms.
All supplemental forms are highly bioavailable.
* Glucosamine-6-Phosphate (G6P) and N-Acetyl-Glucosamine (NAG) are naturally present within the human body.
- NAG is converted to hyaluronic acid (HLA) as needed. HLA is an important component of synovial fluid.
* Glucosamine sulphate is sourced from marine exoskeletons (so not suitable for vegetarians, vegans and those with seafood allergies). It appears to be absorbed better and hence result in higher tissue concentrations. Sulphate is
found in synovial fluid and is required for GAG synthesis.
* Glucosamine hydrochloride is created synthetically from corn.
Name 3 ways that glucosamine is useful for osteoarthritis
- Stimulates metabolism of chondrocytes in the articular cartilage and synovial cells in the synovial tissue. This slows joint degeneration and prevents joint space narrowing.
- Decreases inflammation by inhibiting the formation of cytokines such as interleukin-1.
- Pain reduction is comparable to NSAIDS. NSAIDS provide relief after two weeks compared to four to eight weeks for glucosamine sulphate.
- Less effective for severe, long-standing osteoarthritis.
- More effective combined with chondroitin and MSM.
- Dosage: 1500 mg daily or in three divided doses.
How is glucosamine useful in IBD?
NAG supports the GI epithelial barrier by enhancing mucin functionality, which is dramatically altered in those with IBD. Mucins are a group of proteins found in mucus that form a barrier and prevent microbial overgrowth.
* NAG also reduces biofilm formation associated with IBD.
* NAG can be also used in intestinal permeability.
- Dosage: 3–6 g daily for children; 6 g daily for adults in three divided doses. Administered orally or rectally.
When supplementing with glucosamine what precautions should be taken?
Are there any adverse effects to be aware of?
What are the drug interactions with glucosamine?
Supplementation:
* Caution: Glucosamine supplements can be synthesised in the laboratory, however most are produced from the shells of crustaceans — so can be problematic for those with a seafood allergy.
- Mild adverse effects: GIT symptoms such as nausea, heartburn, diarrhoea, constipation as well as drowsiness, skin reactions and headaches.
- Interactions: Potential increase in the anticoagulant effect of warfarin, leading to increased risk of bleeding and bruising.
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What is chondroitin sulphate?
Where can it be found in the human body?
Chondroitin sulphate is a type of glycosaminoglycan (GAG).
* It is a major component of the extracellular matrix of many
connective tissues. Most notably, this includes cartilage and joint connective tissue.
* Chondroitin provides resistance to compression, partially by thickening synovial fluid.
How is chondroitin sulphate useful for osteoarthritis?
Protects cartilage from degradation by:
- Reducing degradative enzymes.
- Decreasing inflammation — reduces inflammatory intermediates such as COX-2. This is also seen by reductions in the inflammatory marker ‘CRP’.
- Increasing hyaluronic acid synthesis — enhancing joint lubrication.
- Dosage: 200–400 mg two to three times a day or 1000–1200 mg daily as a single dose.
When supplementing with chondroitin sulphate what precautions should be taken?
Are there any adverse effects to be aware of?
What are the drug interactions with chondroitin sulphate?
Supplementation:
* Supplemental chondroitin is usually well tolerated. Studies show that people absorb only 8–18% of orally-administered chondroitin.
- Safety: There is some concern that chondroitin might exacerbate asthma. Patients with asthma tend to have higher concentrations of chondroitin antibodies in the airway compared to people without asthma.
- Interactions: Potential increase in the anticoagulant effect of warfarin, leading to increased risk of bleeding and bruising
What is methyl sulfonylmethane (MSM)?
Name 2 plant sources of MSM
Name an animal source of MSM
Methyl sulfonylmethane (MSM) is a source of sulphur used by plants to create the amino acids, cysteine and methionine. These amino acids are a dietary source of sulphur.
* Plant food sources: Green leafy vegetables, alfalfa sprouts, algae, fruits, vegetables, and grains.
* Animal sources: Milk (cows).
How is MSM useful for osteoarthritis?
- Alone or in combination with glucosamine / chondroitin, it can reduce pain and swelling and improve joint function.
- General anti-inflammatory properties by inhibiting the secretion of cytokines (IL-6 and TNF-α) and COX-2.
- Sulphur is a component of cartilage and so exerts a protective effect on cartilage.
- Dosage: 500 mg three times a day.
How is MSM useful for cardiovascular health?
- MSM reduces homocysteine levels (by donating methyl groups) and reduces lipid peroxidation.
- This protects the vascular endothelium from damage.
- Dosage: 3 g per day (benefits observed at 28 days).
How is MSM useful for tissue repair?
- Decreases oxidative stress and inflammation which helps to repair GI mucosal injury and ↓ chronic GI inflammation.
- Supports tissue healing after an injury (including the skin).
- Can be applied topically to affected skin.
- Dosage: 2 g two to three times daily.
How is MSM useful as an immune modulator?
- The immune-regulating and antioxidant properties of MSM make it useful for seasonal allergies and ↓ inflammation.
- Studies show that MSM inhibits NF-κB activity, downregulating inflammatory cytokines.
- Dosage: 2.6 g per day for seasonal allergies
