16/04/2015
Effective Anti-Inflammatory and
Pain Killing Supplements
Normal and Osteoarthritic Knee Joint
(Fibroblasts)
James Meschino DC, MS, ND
Associate Professor: CMCC – division
of physiology and biochemistry
Natural Management of MSK Pain and
Inflammation
Factors Affected By Diet, Exercise and Supplements:
1.
2.
3.
4.
5.
6.
7.
Joint Cartilage Synthesis and Integrity
Hyaluronic Acid Synthesis
Collagen Synthesis
Prostaglandins
TNF-alpha
NF-kb
Opioid Receptors and Serotonin Receptors
• Decreased glucosamine synthesis after age 40
is major contributing factor to OA
• Results in cartilage erosion, narrowed jt space,
with pain, inflammation, stiffness and
deformity
Osteoarthritis and Cartilage Injury
• Osteoarthritis: most common joint disease in
humans and vertebrate animals
• 50% pop affected by age 65
• Virtually everyone affected past 75 yrs
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• Chondroitin sulfate (proteoglycan) is formed from
glucuronic acid and N-acetyl galactosamine
(repeating disaccharide)
• Chondroitin is the mortar btw the bricks (collagen)
within joint cartilage
• Bottle Brush appearance with a protein stem
Cartilage Erosion From Decrease
Glucosamine Synthesis
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Does Glucosamine Supplementation Work?
• Chondroitin Sulfate:
– Shock absorbing due to negative charges repel
– Shock absorbing due to water magnet effect
(cartilage matrix is 75-80% water by weight)
• A 2012 review paper in the journal Therapeutic Advances in
Musculoskeletal Disease instructs medical doctors to use
glucosamine sulfate in the management of osteoarthritis.
• Medical researchers point out, clinical studies prove that
glucosamine sulfate (not other forms of glucosamine) block
the release of inflammatory chemicals (NF-kb, interleukin-1)
found in osteoarthritis, and Glucosamine sulfate is also the
only known substance that blocks the destruction of joint
cartilage – the hallmark feature in osteoarthritis.
•
• Glucosamine Clinical Studies:
– Proven to slow or halt cartilage erosion
– Reduces pain, swelling, stiffness
– Increases hyaluronic acid (increasing viscosity)
– Increases collagen synthesis from chondocytes
(exercise also stims)
Lead Researher: Lucio C. Rovati, MD
Chief Scientific Officer, Rottapharm|Madaus, Via Valosa di Sopra, 9, 20900 Monza (MB), Italy
Glucosamine and Rheumatoid Arthritis
• Glucosamine improved symptoms in patients suffering
with rheumatoid arthritis, according to the results of a
study published in the September 2006 issue of
"Rheumatology International.“
• This double-blind placebo-controlled study showed a
remarkable decrease in pain and swelling associated
with rheumatoid arthritis when glucosamine was used
at a dose of 1,500 mg per day.
Source: http://www.livestrong.com/article/363893glucosamine-for-rheumatoid-arthritis/#ixzz1sEUn7zAO
• Glucosamine Clinical Studies:
• Sulfur also acts as anti-inflammatory
– Equal or better to NSAIDS in controlling OA
– Less frequent side effects than NSAIDS (6% vs
16%)
– Less severe side effects than NSAIDS
• MSM shown to be useful for OA and other joint
inflammatory conditions
• Best to combine Glucosamine sulfate with
MSM
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Glucosamine and MSM
MSM: much anecdotal evidence for MSM relieving pain and
inflammation. Sulfur is required to stabilize cartilage.
A 2009 experimental study showed anti-inflammatory
mechanisms through which MSM likely works in humans:
MSM reduced synthesis of PG-2
MSM reduced synthesis of Interleukin-6
MSM reduced levels of TNF alpha
MSM reduced activity of NF-kappa beta
“Collectively, theses results indicate that MSM inhibits LPSinduced release of pro-inflammatory mediators in murine
(mouse) macrophages through down-regulation of NF-kappaB
signaling”
Source: (http://www.ncbi.nlm.nih.gov/pubmed/19336900)
Glucosamine Dosing:
• Anti-aging (after 40): 500-1,000 mg per day
• OA and other cartilage problems: 1500-2,000
mg per day (sports injuries)
• 10 mg/lb in younger persons
Other concerns related to glucosamine:
1. Can be used in patients with sulfa allergies or
sensitivities
2. No reported adverse reactions in patients with
seafood allergies (mined from shells of shell
fish- pharmaceutical grade, pure)
3. Diabetics- monitor blood sugar
4. Monitor blood pressure in early stages
Example of Glucosamine/Anti-inflammatory
Supplement:
– Glucosamine Sulfate – 500 mg
– Quercetin – 100 mg
– Bromelain Enzymes – 100 mg
– MSM – 133.3
Dosage:
1-2/d for prevention
3-4/d for therapeutic purposes
Polyunsaturated Fats and Inflammation
• Glucosamine Side Effects: (Rare):
– GI upset
– Drowsiness
– Skin reaction
– Headache
Minor compared to NSAIDS (bleeding, organ
toxicity)
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Lifestyle Approach To Reducing
Inflammation
ALA Blocks Conv of Linoleic to AA via delta 6 competition
ALA uses up delta-5 desaturase enzyme, enabling GLA to competes with AA
Omega-3 also inhibits TNF-alpha and Interleukin-1 (pro-inflammatory cytokines)
Essential Fatty Acids:
1. Reduce build up of Arachidonic acid -precursor to
PG-2 (pro-inflammatory):
Avoid high fat meats and high fat dairy products
Use olive, canola, and peanut oil in place of other oils
high in linoleic acid
2. Reduce intake of alcohol, hydrogenated fats – encourage
production of PG-2
3. Ensure status of B-vitamins, antioxidants, magnesium and zinc
– promote PG-1 and PG-2 pathways as coenzymes:
•
•
•
•
•
•
•
Vitamin C – 1,000 mg
Vitamin E – 400 IU
Selenium – 100- 200 mcg
Zinc – 15-25 mg
Magnesium – 250- 500 mg
Vitamin B6 – 50 – 100 mg
Vitamin D – 1000 IU
Hence – High Potency Multiple Vitamin and Mineral
Example of Essential Oils Supplement
High Potency
Multiple Vitamin and Mineral
One capsule contains:
1. Fish Oil – 400 mg (30% EPA/20% DHA = 50% EFA)
2. Flaxseed Oil – 400 mg (58% ALA)
3. Borage Seed Oil – 400 mg (22% GLA)
Dosage: 3 capsules per day for maintenance (double
dosage for therapeutic purposes)
Vitamin A
Retinyl Palmitate
Beta Carotene
2,500 I.U.
10,000 I.U.
Vitamin C
Ascorbic Acid
Vitamin D
Cholecalciferol
1000 I.U.
Vitamin E
D-alpha tocopheryl
400 I.U. (natural)
Thiamin
Thiamine Mononitrate
50 mg
Riboflavin
1,000 mg
50 mg
Niacin
Niacinamide
Vitamin B-6
Pyridoxine
Hydrochloride
Folic Acid
50 mg
50 mg
400 mcg
Vitamin B-12
Cyanocobalmin
50 mcg
Biotin
D-Biotin
300 mcg
Pantothenic Acid
Calcium Pantothenate
50 mg
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High Potency
Multiple Vitamin and Mineral cont…
Anti-Inflammatory Herbs
1. Curcumin:
Calcium
Calcium Carbonate,
Citrate
500 mg
Iron
Ferrous Fumarate
6 mg
Magnesium
Magnesium Oxide
200 mg
Zinc
Zinc Citrate
15 mg
Selenium
Selenium HVP/HAP
Chelate
200 mcg
2 mg
Copper
Copper Gluconate
Manganese
Manganese Gluconate
5 mg
Chromium
Chromium Amino Acid
Chelate
50 mcg
Molybdenum
Molybdenum Citrate
50 mcg
Bioflavonoids
50 mg
Lutein
6 mg
Lycopene
6 mg
4. Supplement with Borage, Flaxseed and High
Yield Fish Oil
Also note that:
GLA precurson to PG-1 (anti-inflam). The body slowly
converts LA to GLA, and conversion is greatly reduced with
aging, diabetes, PMS, Eczema, inflammatory conditions,
and In First Nations People and African-Americans (Thus,
borage oil optimizes PG-1 production for these patients)
– Derived from spice turmeric
– Inhibits 5-lipoxygenase and cyclooxygenase
enzyme
– Equal success to phenylbutazone
– Standardized grade (90-95% curcumin)
– Rare side effects: dyspepsia, reflux
– Precaution: mild anticoagulant (no reports)
2. Boswellia:
– Derived from gum resin of boswellia tree
– Boswellic acids are noted active ingredients
– Standardized grade is 70% boswellic acids
– Inhibit 5-lipoxygenase
– Clinical Success: OA and RA
– No reported side effects or precautions
Anti-inflammatory Herbs:
Curcumin Blocks 5 & 12 Lipoxygenase
Boswellia & Ginger Block 5 Lipoxygenase
White Willow Extract, Curcumin & Ginger Block COX
PLA2 inhibited by EPA
3. White Willow Bark Extract:
– Derived from willow bark
– Active ingredients: salicin and other phenolic
glycosides (std to 15% salacin content)
– Inhibit CO and provide mild analgesic effect
– Acts like slow release ASA, but no GI irritation
– Clin Success: OA, RA, back pain and knee OA
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4. White Willow Bark Extract:
– No Bleeding disorders (no platelet effects)
– Contraindications: gout, hemophilia, kidney
disease, active ulcer, children under 12
Bromelain:
– No significant side effects
– Precautions: mild anticoagulant (no reports)
– Rare side effects: nausea, headache, dyspepsia
5. Ginger Root Extract:
– Active ingredients are gingerols (oleoresins)
– Inhibit CO and 5-lipoxygenase
– Std to 5% gingerol content
– Clinical Success: OA, RA, Myalgias
– Rare Side Effects: dyspepsia
– Precautions: mild anticoagulant (no reports)
6. Bromelain:
– Contains anti-inflammatory and fibrinolytic
enzymes (brks down fibrin clot in swelling)
– Clinical Success: inflammation from trauma
(sports injuries, car accidents), OA, RA and other
inflammatory joint problems)
7. Quercetin:
– Flavonoid found in onions and apples
– Blocks release of histamine and other inflam.
Enzymes
– Anecdotal and experimental studies: Arthritis and
Allergies (no side effects or precautions)
8. Devil’s Claw:
– Contains harpogosides and other agents
– Unknown anti-inflam action (contradictory
findings)
– Strong anecdotal support, but studies lacking
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•
Osteoarthritis with pronounced inflammatory
component (used in combination with
Glucsomaine Joint Forumula)
•
Post-traumatic joint inflammation (e.g. whiplash,
sports injury)
•
Also: Cancer Prevention (Colon, Breast, Prostate) down regulation of epidermal growth factor
receptors, and cyclo-oxygenase and lipoxygenase
inhibition, decreasing formation of eicosanoids
derived from Arachidonic Acid
Devil’s Claw:
– Rare side effects: GI upset
– Precautions: Bleeding disorders reported
– Contraindications: anticoagulant drugs, history of
ulcer (can reactivate via increased gastric
secretions)
Autoimmune Conditions:
Example of Natural Anti-inflammatory Combo
Supplement (amt per capsule):
1.
2.
3.
4.
Curcumin – 200 mg
Boswellia (70% boswellic acids) – 200 mg
White willow extract (15% salicin) – 33.33 mg
Ginger root (5% gingerols) – 50 mg
– Dosage: 1-4 capsules, up to three times per day
Clinical Applications For Natural Anti-inflammatory
Herb Combo Supplement
Natural Bio-Regulation Of TNF: TNF or the effects of TNF are
inhibited by a number of natural compounds, including:
Curcumin
Quercetin
Catechins
These agents are not associated with side effects.
Curcumin Refernces:
• Siddiqui AM, Cui X, Wu R, et al. (July 2006). "The anti-inflammatory effect of curcumin in an
experimental model of sepsis is mediated by up-regulation of peroxisome proliferatoractivated receptor-gamma". Crit. Care Med. 34 (7): 1874–82.
•
Okunieff P, Xu J, Hu D, et al. (July 2006). "Curcumin protects against radiation-induced acute
and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and
fibrogenic cytokines". Int. J. Radiat. Oncol. Biol. Phys. 65 (3): 890–8.
• Gulcubuk A, Altunatmaz K, Sonmez K, et al. (February 2006). "Effects of curcumin on tumour
necrosis factor-alpha and interleukin-6 in the late phase of experimental acute pancreatitis". J
Vet Med a Physiol Pathol Clin Med 53 (1): 49–54.
•
Lantz RC, Chen GJ, Solyom AM, Jolad SD, Timmermann BN (June 2005). "The effect of
turmeric extracts on inflammatory mediator production". Phytomedicine 12 (6-7): 445–52..
Three Pathways Activated By TNF-alpha
Musculoskeletal Inflammatory States:
• Tendonitis
• Rheumatoid arthritis and associated connective
tissue disorders
• Bursitis
• Fascitis
• Muscle inflammation
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Natural Inhibitors of Inhibit NF-kb:
Curcumin (plus LOX, COX, TNF-alpha, Her-2 inhibition)
Ginger
Quercetin
Antioxidants (Vitamin C, Vitamin E)
EPA and DHA
Reishi mushroom extract
Other:
Anthocyanidins (berrries)
N-acetyl cysteine (NAC)
Isoflavones
Pomegranate
Baicalein
Parthenolide
Clinical Studies:
• California Poppy Supplementation has been
shown to relieve pain by acting on several
different pain receptors in the body including
opioid and serotonin receptors.
• It is not known to cause physical dependence or
addiction.
• It has also been shown to be a hypnotic drug (i.e.,
sleep aid).
Adeeva Nyquinadol
Natural Alternative to Opioid Drugs
California Poppy (Eschscholzia californica) –
active constituents in the California Poppy
bind to opioid and serotonin receptors,
relieving pain, without producing euphoria or
having addiction potential
California Poppy has been shown an safe and
effective alternative to benzodiazepine and
narcotic drugs
What is medicinal grade:
• Standardized to contain 0.8% of the three
isoquinoline alkaloids:
• californidine
• escholtzine
• and protopine.
Health Canada Approval for Adeeva Nyquinadol
(NPN – 80032386)
The NHPD Monograph for California Poppy allows
for the following use:
• Traditionally used in Herbal Medicine as a mild
sedative and/or sleep aid (hypnotic).
• Traditionally used in Herbal Medicine as an
analgesic
Drug-Nutrient Interactions: Cannot take CP
supplements concurrently with:
1.
2.
3.
4.
Sleeping Aids, including benzodiazepines
Narcotic Drugs
Tranquilizers
Anti-anxiety drugs of any kind
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Dosage:
• Capsule - 500 mg California poppy extract (6:1
extract)
Usual dose:
• One capsule, one hour before bedtime
• In some cases, two capsules is required
Summary: Natural Management Of Inflammatory
Diseases And Autoimmune Diseases
Objectives:
1. Glucosamine Sulfate if cartilage erosion
concerns (40 yrs old, OA, RA, cartilage injury)
2. Decrease synthesis of PG-2, and increase
synthesis of PG-1 and PG-3
3. California poppy to control night pain
4. Decrease synthesis of TNF-alpha - autoimmune
5. Inhibit activity of NF-kb - autoimmune
6. Bioregulation of Immune System - autoimmune
Supplementation Considerations To Reduce Inflammation and Help
Control Autoimmune Diseases
1.
2.
3.
4.
5.
6.
Essential Oils flaxseed, borage seed and fish oil) - 3-6 caps/d
Natural Anti-inflammatory Combo – (curcumin, boswellia,
ginger, white willow extract) - up to 4 caps, 3 times/d
Multiple Vitamin & Mineral (B-vits, antioxidants, magnesium)
Additional – Quercetin – up to 2000 mg/d
Vitamin D – 5,000 – 10,000 IU daily (increased IL-4, which is
an anti-inflammatory cytokine)
Additional Antioxidants (vitamin C – 5000 mg, Vitamin E –
1000 – 2000 IU, Selenium – 200-400 mcg
Autoimmune Also Consider:
1. Probiotics – immune regulation
2. Digestive Enzymes with Prebiotics
3. Immune and Detox Support Supplement – 4 caps/d (reishi
mushroom extract, astragalus, milk thistle, indole-3 carbinol)
Supplementation
Other Considerations:
4. If under stress – Adrenal Support Formula – 4 caps for 2 weeks,
then 2 caps/d – with adaptogen herbs to decrease cortisol
release from adrenals
5. Mushroom Harvest – 14 mushroom blend (20% beta-glucan
content) (www.mushroomharvest.com) – 2 teaspoons per
day=4gms of mushroom blend – excellent delivery system of
high dose beta-glucans for therapeutic purposes (mix into
juice, shake or sprinkle on cereal, in yogurt or other foods
(salad etc).
Implementation
Diet and Lifestyle:
• Low animal fat diet (except fish) – reducing arachidonic acid
and linoleic acid
• Minimize intake of transfats and alcohol
• Replace vegetable oils with olive oil, flaxseed oil, grape seed oil
(canola oil)
• Reduce Body Fat
• Endurance Exercise
• No smoking
• Deep breathing, visualization (mind-body work)
Therapies:
• Electromodalities, including electroacupuncture
• Chiropractic
• Massage – soft tissue etc
Migraine Treatment and Prevention Agents
• Migraine headaches: afflict 1 in 19 adults, of which 75% are women
• Migraines also occur in an estimated 3% to 7% of all children
Drug Management:
A. Fiorinal
Fiorinal and Firoinal-type drugs are a 3-in-1 analgesics consisting of:
1.
aspirin or acetaminophen
2.
the barbiturate - butalbital
3.
caffeine.
•
Some formulations Fiorinal #3- contain the opioid codeine.
•
Prescribed most often for tension headaches and migraines.
Since butalbital is habit-forming, using fiorinal daily can lead to dependency.
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C. Ergot alkaloids
Fiorinal #3 contains:
30 mg codeine
50 mg butalbital
40 mg caffeine
and 325 mg aspirin.
Other brand names include Fiormor, Fiortal, Fortabs,
and Laniroif.
B. 5-Hydroxytryptophan receptor agonists (Triptans):
Triptans treat an acute migraine attack by narrowing blood vessels
in the brain and balancing brain chemicals (e.g. increasing
serotonin)
Common Triptans:
• almotriptan (Axert®)
• eletriptan (Relpax®)
• naratriptan (Amerge®)
• rizatriptan (Maxalt®, Maxalt RPD®)
• sumatriptan (Imitrex®, and generics): tablet, injection with Autoinjector, and nasal spray
• zolmitriptan (Zomig®, Zomig Nasal Spray®, Zomig Rapimelt®): tablet,
nasal spray, and orally disintegrating tablet
Precautions: Triptans should not be used by
anyone with heart disease, uncontrolled high
blood pressure, blood vessel disease, or a
history of stroke, due to vasoconstriction
effect.
Ergots treat migraine onset by narrowing the
blood vessels in the brain.
Common Brands:
• dihydroergotamine injection (DHE®) and nasal
spray (Migranal®)
• ergotamine with caffeine (Cafergot® suppositories
and tablets)
• ergotamine with caffeine and diphenhydramine
(Gravergol® capsules)
Side Effects of Ergots include:
chest pain, tingling or burning sensations,
nausea, vomiting, and cramps.
Rarely, they may reduce the blood flow to
extremities (hands and feet), which, in severe
cases, may lead to tissue damage
* Migraine Drugs are used only at migraine
onset, to help abort the episode, but should
not be used daily for prevention
Migraine Prevention:
1. Feverfew and Butterbur supplementation
Example: MigranEx Supplement (non-addictive, no side
effects)
2. Check for food allergies/sensitivities (and environmental
triggers) – Integrative Medical Doctor
3. Chiropractic Care – to relieve nerve irritation from spinal
fixations and/or soft tissue impingement of spinal nerves
4. Meditation/Mind-Body Techniques (e.g. yoga)
5. B-Vitamin Supplementation (and magnesium)
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Supplements Shown To Prevent Migraines:
1. Butterbur (an herb)
Active Constituents - pentasin and isopetasin:
Mechanism of Action:
• Inhibit the synthesis of inflammatory chemicals such as leukotrienes
and prostaglandin E2, which can trigger migraines.
• Antispasmodic effect on vascular walls and appear to have an
affinity for cerebral blood vessels.
• Natural beta blocker, stabilizing normal flow of blood to the brain.
This action helps control blood pressure and prevents spasm of
blood vessels, which are also key processes in preventing the onset
and progression of migraines.
Recent Studies With Butterbur:
• Double-blind ( journal Neurology in 2004 - Lipton RB et al),
researchers gave 202 migraine sufferers butterbur extract or a
placebo for a three month period.
After 12 weeks, butterbur supplemented group reported
approximately 50% fewer migraines than usual.
• 12- week, double-blind study published in 2000 in the journal,
Headache, (Mauskop A et al), 58 migraine sufferers were given
butterbur extract or a placebo twice daily
Butterbur group had 50 percent fewer migraines than usual, while
the placebo group dropped only 10 percent
•
Butterbur supplementation was shown to lower the incidence of
migraines in children and adolescents by 77%, according to a 4month trial published in the journal, Headache (Pothmann R et al
2003).
2. Feverfew (an herb)
Active Constituent: Parthenolide
Mechanism of Action:
• Relieves smooth muscle spasms - helps prevent the constriction of blood vessels in
the brain
•
Like butterbur, parthenolide also inhibits the production of prostaglandin
hormones that cause inflammation of blood vessels.
•
Inhibits excessive aggregating of platelets, which also normalizes blood flow.
Recent Studies:
• A survey of 270 migraine sufferers in Great Britain revealed that more than 70% of
individuals saw improvement in migraine frequency and severity, after using
feverfew for migraine control (University of Maryland Study – 2009).
•
Clinical Drug Investigation (Shrivastava R et al, 2006) and the journal, Headache
(2004), showed that supplements containing a standardized extract of feverfew
reduced migraine attacks by 50%, in chronic migraine sufferers (Maizels M et al,
2004).
Dosage:
1.
Adults - 325 mg (standardized grade of parthenolide
concentration of 0.7 %), twice daily
2.
Children – single dose of 325 mg (same standardized grade as
above), in children 6 years and older
Example of Migraine Prevention Combination Supplement
One Capsule Contains:
1. Butterbur Root – 75 mg (standardized to minimum 15%
sesquiterpenes as petasines)
2. Feverfew – 325 mg (standardized grade of parthenolide
concentration of 0.7 %)
Adults – one capsule, twice daily for prevention
Children – one capsule per day for prevention
B-Vitamins and Migraines
Dosage:
1. Adults - 75 mg (standardized to minimum
15% sesquiterpenes as petasines), twice per
day.
2. Children - Single dose of 75 mg per day can
be used for children six years and older as
well as teenagers
• A 2004 study in The European Journal of Neurology showed that
high dose Vitamin B2 (riboflavin) supplementation reduced
migraine frequency and severity in migraine sufferers.
• More recently, the study published in Pharmacogenetics and
Genomics (2009) by R. Lea and fellow researchers showed that Bvitamin supplementation with folic acid, riboflavin and vitamin B12
reduced migraine severity and frequency to a significant degree
compared to those given the placebo pill, in a study involving 57
migraine sufferers.
The B-vitamin daily dosages were:
•
Folic acid – 2 mg (2000 mcg) – very high dose (cancer risk?)
•
Riboflavin – 25 mg
•
Vitamin B12 – 400 mcg
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• The B-vitamin supplemented group also realized a 39%
decrease in their blood homocysteine levels.
• Homocysteine is a dangerous substance that has been
shown to cause about 10% of all heart attacks each year.
Therefore, keeping homocysteine lower is very desirable.
• Some evidence suggests that homocysteine may also
contribute to susceptibility to migraine headaches, and
thus lowering homocysteine may reduce migraine attacks,
as realized in this 2009 study.
Magnesium Supplementation – may also be helpful (5001000 mg per day). Not to be given to patients with chronic
renal failure or any kidney disease
Thank You
Contact Information:
Dr James Meschino DC, MS, ND
[email protected]
Phone: 1-888-251-1010 ext 383
www.meschinohealth.com (many of published
research review papers can found here)
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