Posts

ADHD and Magnesium

Magnesium deficiencyMagnesium deficiency has been reported in children with ADHD syndrome.  Signs of this malady include hyperactivity, hypermotivity with aggressiveness, and lack of attention, especially at school.  Biochemical and concurrent behavioral improvements have been realized by magnesium therapy in association with vitamin B6 supplementation.

An analysis of eighteen different study groups performed by Marianne Moussain-Bosc and her colleagues at a French institute for nervous system studies in 2006 indicated that ,”…B6/magnesium therapy benefits about half of autistic children,” but also noted that a related study showed benefits to those with ADHD, using the same doses of each supplement.  Children ranging from one to ten years of age “…received 0.6 milligrams per kilogram per day of vitamin B6 and 6 milligrams per kilogram per day of magnesium.  Treatment lasted an average of eight months.”  (Moussain-Bosc. 2006)   Both groups of children had significantly lower values of erythrocyte magnesium at the outset than the control group(s).  It was observed that after two months of the vitamin-mineral regimen there was a substantial change in clinical symptoms.

ADD and ADHD are on the upswing, and have been for some time.  Both conditions are hastily treated with drugs, often without a differential diagnosis, which is essentially a process of elimination.  Instead, the Diagnostic and Statistical Manual (DSM) of Mental Disorders criteria, and a series of observations and teacher questionnaires are employed.  (Pediatrics. 2000. No authors listed.)   Mineral and electrolyte imbalances are awfully hard to discover with that technique, don’t you think? Most parents wince at the thought of dosing their kids with “miracle” substances that have unknown long-term side effects. On the other hand, the clueless, self-centered, entitled faction applauds the quiet, calm, relatively immobile zombie of the house.

Although we live in plentiful times, where food, shelter, and clothing are accessible to all who earn them, there still exist children who are seriously shy of their required magnesium stores.  One reason is stress.  The number of stressors to which kids are exposed grows every year.  From sports practice, to violence in the streets and on television, to academic obligations, to peer pressure and self-image, and more, the kids are overloaded.  It’s the accompanying flood of adrenaline that siphons magnesium, since that hormone needs the mineral for its release.  Another reason is poor nutrition.  You know, processed foods, refined sugars, colorful and flavorful additives, artificial this and that…  This kind of diet is notoriously low in magnesium, which is calming to the nervous system.  The refined sugars and additives actually stress the body, especially the nervous system, as it tries to overcome the onslaught.  A double whammy.

In Poland, researchers studied ADHD children and assessed the value of magnesium supplementation on the DSM parameters, finding that six months of taking as little as 200 mg a day yielded a decrease in symptoms.  (Starobrat-Hermelin. 1997)  Later study performed by Moussain-Bosc saw a decrease in ADHD symptoms using a combined magnesium / B6 regimen in several dozens of children with low red blood cell magnesium stores.  (Moussain-Bosc. 2004)

Attention deficit hyperactivity disorder is a developmental perturbation characterized by attention problems and hyperactive behavior.  It’s the most commonly studied psychiatric disorder in children, affecting three to five percent of children worldwide.  Sadly, integrative therapies are spurned by traditional-minded doctors, so parents have taken it upon themselves to intervene, despite the lack of support from their physicians.

Bearing in mind that sugar has a nutrient-diluting effect might make a difference in ADHD management and magnesium stores in the body.  It’s normal to wonder where all the magnesium goes.  Doesn’t it stay still?  After all, it’s part of bone.  That’s true, but magnesium is also an electrolyte, helping to send calming electrical messages across the membrane of each cell, making it a natural calcium channel blocker.  It gets used up in the manufacture of more than three hundred enzymes the body needs, including those that make anti-inflammatory chemicals from fatty acids.  Situations and conditions within the body can push this mineral into the urine and then into the toilet.  Sugar intake, and even that of simple carbohydrates, increases the secretion of insulin by the pancreas.   Increased insulin, as might be found in insulin resistance, pushes magnesium out.  (Huerta. 2005)  The pancreas needs magnesium to make its other secretions, including those that break down proteins (trypsin and chymotripsin) and fats (lipase), as well as carbohydrates.  Carol Ballew and her colleagues found that carbonated beverages, namely soda, are negatively associated with magnesium levels This starts a vicious cycle because low magnesium is related to insulin resistance. (Ballew. 2000).

In tests done in the mid 90’s, it was discovered that elevated insulin levels result in increased magnesium excretion.  These researchers noted this as the explanation to the magnesium deficit that accompanies obesity, diabetes, and hypertension, as well as hyperinsulinemia.  (Djurhuus. 1995)  This same group later reported that high glucose levels, such as would come from a sugary breakfast or a plethora of sweet goodies, raise magnesium excretion by a factor greater than 2.0.  (Djurhuus. 2000)

The foods that once supplied dietary magnesium have become compromised by careless farming, harvesting, processing, storage, and handling practices.  We now get more calcium and less magnesium than ever in the history of mankind.  Sugar erases magnesium from the body’s slate. (Fuchs. 2002) (Tjaderhane. 1998) (Milne. 2000)  It’s time to put it back.  At 6.0 mg / kg / day, that equates to about 3.0 milligrams per pound of body weight…for all of us.

References

  • AUTISM RESEARCH REVIEW INTERNATIONAL Vol. 20, No.3, 2006
    Studies confirm benefits of vitamin B6/magnesium therapy for autism, PDD, and ADHD
    No Authors Cited

    +

  • Magnes Res. 1997 Jun;10(2):143-8.
    Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD).
    Kozielec T, Starobrat-Hermelin B.

    +

  • Pediatrics. 2000 May;105(5):1158-70
    Did not perform differentiated diagnosis
    Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. American Academy of Pediatrics.
    No authors listed

    +

  • Magnes Res. 2006 Mar;19(1):53-62.
    Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism.
    Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP.

    +

  • J Am Coll Nutr. 2004 Oct;23(5):545S-548S.
    Magnesium VitB6 intake reduces central nervous system hyperexcitability in children.
    Mousain-Bosc M, Roche M, Rapin J, Bali JP.

    +

  • J Clin Invest. 1970 July; 49(7): 1458–1465.
    A comparison of the effects of glucose ingestion and NH4Cl acidosis on urinary calcium
    and magnesium excretion in man

    Edward J. Lennon and Walter F. Piering

    +

  • J Abnorm Child Psychol. 1986 Dec;14(4):565-77.
    Behavioral effects of sucrose on preschool children.
    Goldman JA, Lerman RH, Contois JH, Udall JN Jr.

    +

  • Arch Pediatr Adolesc Med. 2000;154:1148-1152
    Beverage Choices Affect Adequacy of Children’s Nutrient Intakes
    Carol Ballew, PhD; Sarah Kuester, MS, RD; Cathleen Gillespie

    +

  • Diabetes Care. 2005 May;28(5):1175-81.
    Magnesium deficiency is associated with insulin resistance in obese children.
    Huerta MG, Roemmich JN, Kington ML, Bovbjerg VE, Weltman AL, Holmes VF, Patrie JT, Rogol AD, Nadler JL.
    SourceUniversity of Virginia, Department of Pediatrics, Box 800386, Charlottesville, VA 22908, USA. [email protected]

    +

  • Diabetic Medicine.  Volume 12, Issue 8, pages 664–669, August 1995
    Insulin Increases Renal Magnesium Excretion: A Possible Cause of Magnesium
    Depletion in Hyperinsulinaemic States

    Dr. M.S. Djurhuus, P. Skøtt, O. Hother-Nielsen, N.A.H. Klitgaard, H. Beck-Nielsen

    +

  • Scan Jou of Clin & Laboratory Investigation. 2000, Vol. 60, No. 5 , Pages 403-410
    Hyperglycaemia enhances renal magnesium excretion in Type 1 diabetic patients
    S. Djurhuus

    +

  • J. Nutr. October 1, 1998 vol. 128 no. 10 1807-1810
    A High Sucrose Diet Decreases the Mechanical Strength of Bones in Growing Rats
    Leo Tjäderhane, and Markku Larmas
    Institute of Dentistry, University of Oulu, 90220 Oulu, Finland

    +

  • J Am Coll Nutr February 2000 vol. 19 no. 1 31-37
    The Interaction Between Dietary Fructose and Magnesium Adversely Affects
    Macromineral Homeostasis in Men

    David B. Milne, PhD and Forrest H. Nielsen, PhD

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Kidney Stones: The Basics

green-healthy-foodUreterolithiasis, renal calculi, nephrolithiasis and kidney stone all mean the same thing:  agony.  The nurse told us the pain is equivalent to passing a five-pound canned ham through the southern end of the digestive system, with the lid opened.  If you’ve never experienced the long road to relief, thank the Creator for being excused.

What causes kidney stones?

There is no single cause, but a combination of factors.  The wrong balance of fluids, minerals and acids can put you on your knees faster than being knighted.  If urine has more crystal-making elements than the fluid can dilute, bingo, you have the makings of a stone…or stones.  In looking for a definitive cause, science has left no stone unturned.  No pun intended.  Beneath one of those stones is fluoride, having been fingered as causative a decade ago, but only in those with symptoms of skeletal fluorosis and the propensity to form stones in the first place (Singh, 2001).  That rules lots of us out.  Whether or not high doses of vitamin C are implicated in the formation of stones is debatable and based on the status of other nutrients.  By itself, vitamin C, chemically known as ascorbic acid, is able to be converted by the body into oxalates, which increases the likelihood of making oxalate stones among stone formers who take more than the recommended upper limit of 2000 mg of vitamin C a day (Massey, 2005). But you gotta be a stone former.  Is that like a mason?   Earlier research found that high intake of vitamin B6, pyridoxine, reduces the risk of stone formation from unrestricted doses of ascorbic acid (Curhan, 1999).   Up to 500 mg of pyridoxine a day was found to be useful in the control of elevated urinary oxalates (Mitwali, 1988).  In a study reported in the New England Journal of Medicine in the dark ages of the last century, the degree of oxaluria dictates the dosage of vitamin B6.  But the degree of supplementation depends on how much B6 comes from food (Yendt, 1985).

What are they made from?

Most stones (~80%) are calcium oxalate calculi, which crystallizes in a hurry.  It’s the stuff that forms a needle-like crust on the inside of a brewery container.  If you swallowed this material, you’d get really sick, and maybe die.  Calcium oxalate crystal formation is one of the effects of ingesting antifreeze.  A small dose of calcium oxalate will make your tongue burn and swell your throat shut.  This is what happens when the cat chews on a Dieffenbachia leaf in the living room window, and then requires a trip to the vet.

Some plants, including spinach, contain calcium oxalate in their leaves. If you’re a stone former, you might choose to avoid, or at least limit, raw spinach salads, although some researchers say it doesn’t matter, as long as you’re amply hydrated and your diet is sufficiently balanced to provide calcium and vitamin B6, both of which are found in spinach (Curhan, 1999).  A little baffling, huh?  After a stone passes through the urine and gets collected in that little strainer that painters use to get the globs out of a gallon of linen white, you’ll be asked to take that stone to the doctor so he can determine its makeup.  Then he’ll know what course of action to give you.

How do I prevent kidney stones?

If ever the proverbial ounce of prevention is worth a lot, this is the place.  Most experts agree that drinking fluids is the key.  Believe us when we say that a stone former is more than willing to increase his water intake, despite its lack of flavor.  If you need flavor, try lemon juice.  Counseling in this area is simple:  if you don’t drink enough water, you’ll experience this again.  That means you have to drink even when you’re not thirsty (McCauley, 2012).  Swapping soft drinks for water is prudent (Fink, 2009).

Increasing dietary calcium intake is inversely related to stone formation.  Supplemental calcium, on the other hand, may increase risk.  Dietary calcium blocks the amount of oxalates absorbed by the body, while supplements, especially if taken between meals, spill too much of the mineral into the urine.  If calcium supplementation is needed, take it with a meal to improve absorption.  We’re cautioned not to take more than 500 mg at a time, anyway.  It’s all about the timing (Curhan, 1997).

It’s believed that most stones form in the summer, when people are more likely to get dehydrated, so we’re admonished to drink ten to twelve glasses of water a day.  Other beverages, though, fare well in the prevention category.  Caffeinated and decaffeinated coffee, tea, and wine accounted for a decreased risk of stone formation, according to the Brigham and Women’s Hospital study of the 1990’s (Curhan, 1998).

Obesity increases the risk of kidney stones, but drastic weight loss measures that rely on high protein intake can stymie the good intentions.  So, too, can laxative abuse, rapid loss of lean tissue and, naturally, poor hydration.  A diet high in fruits and vegetables can alkalize urine enough to offset oxalate and uric acid stone formation ( Frassetto, 2011).  Produce is known for its magnesium content.  Intake of magnesium is related to reduced stone manufacture, and has been a recommendation since the 17th century.  Even without overt deficiency, magnesium intake, at 500 mg a day in the form of magnesium hydroxide, was shown to decrease stone formation, and it has no adverse side effects as long as it’s not overzealously done (Johansson, 1980 and 1982).  Too much magnesium may induce laxation.  That’s an individual response.   Later study learned that magnesium combined with vitamin B6 offered a substantial decline in the risk for oxalate stones (Rattan, 1994)

Kale, turnip greens, radishes, chard and other leafy greens, broccoli, Brussels sprouts, and cabbage are good sources of dietary calcium.  Almonds and cashews, pumpkin seeds, barley, quinoa, leafy greens, white and black beans are a few good sources of magnesium.  Since calcium and magnesium compete for occupancy in the body, with calcium the winner, magnesium supplementation is a good idea.  An Epsom salts bath allows magnesium levels to increase transdermally…and it’ll help you fall asleep.  Drink water.  Prevent stones.

References

Conte A, Pizá P, García-Raja A.
Urinary lithogen risk test: usefulness in the evaluation of renal lithiasis treatment using crystallization inhibitors (citrate and phytate).
Arch Esp Urol. 1999 Jan-Feb;52(1):94-9.

Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ.
Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women.
Ann Intern Med. 1997 Apr 1;126(7):497-504.

Curhan GC, Willett WC, Speizer FE, Stampfer MJ.
Beverage use and risk for kidney stones in women.
Ann Intern Med. 1998 Apr 1;128(7):534-40

Curhan GC, Willett WC, Speizer FE, Stampfer MJ.
Intake of vitamins B6 and C and the risk of kidney stones in women.
J Am Soc Nephrol. 1999 Apr;10(4):840-5.

Curhan GC.
Epidemiologic evidence for the role of oxalate in idiopathic nephrolithiasis.
J Endourol. 1999 Nov;13(9):629-31.

Fink HA, Akornor JW, Garimella PS, MacDonald R, Cutting A, Rutks IR, Monga M, Wilt TJ.
Diet, fluid, or supplements for secondary prevention of nephrolithiasis: a systematic review and meta-analysis of randomized trials.
Eur Urol. 2009 Jul;56(1):72-80. Epub 2009 Mar 13.

Frassetto L, Kohlstadt I.
Treatment and prevention of kidney stones: an update.
Am Fam Physician. 2011 Dec 1;84(11):1234-42.

Gill HS, Rose GA.
Mild metabolic hyperoxaluria and its response to pyridoxine.
Urol Int. 1986;41(5):393-6.

Grases F, Costa-Bauzá A.
Phytate (IP6) is a powerful agent for preventing calcifications in biological fluids: usefulness in renal lithiasis treatment.
Anticancer Res. 1999 Sep-Oct;19(5A):3717-22.

Habbig S, Beck BB, Hoppe B.
Nephrocalcinosis and urolithiasis in children.
Kidney Int. 2011 Dec;80(12):1278-91. doi: 10.1038/ki.2011.336. Epub 2011 Sep 28.

Johansson G, Backman U, Danielson BG, Fellström B, Ljunghall S, Wikström B.
Biochemical and clinical effects of the prophylactic treatment of renal calcium stones with magnesium hydroxide.
J Urol. 1980 Dec;124(6):770-4.

Johansson G, Backman U, Danielson BG, Fellström B, Ljunghall S, Wikström B.
Effects of magnesium hydroxide in renal stone disease.
J Am Coll Nutr. 1982;1(2):179-85.

Massey LK, Liebman M, Kynast-Gales SA.
Ascorbate increases human oxaluria and kidney stone risk.
J Nutr. 2005 Jul;135(7):1673-7.

McCauley LR, Dyer AJ, Stern K, Hicks T, Nguyen MM.
Factors influencing fluid intake behavior among kidney stone formers.
J Urol. 2012 Apr;187(4):1282-6. Epub 2012 Feb 15.

Miggiano GA, Migneco MG.
[Diet and nutrition in nephrolitiasis].   [Article in Italian]
Clin Ter. 2007 Jan-Feb;158(1):49-54.

Mitwalli A, Ayiomamitis A, Grass L, Oreopoulos DG.
Control of hyperoxaluria with large doses of pyridoxine in patients with kidney stones.
Int Urol Nephrol. 1988;20(4):353-9.

Moyad MA.
Calcium oxalate kidney stones: another reason to encourage moderate calcium intakes and other dietary changes.
Urol Nurs. 2003 Aug;23(4):310-3.

Rattan V, Sidhu H, Vaidyanathan S, Thind SK, Nath R.
Effect of combined supplementation of magnesium oxide and pyridoxine in calcium-oxalate stone formers.
Urol Res. 1994;22(3):161-5.

Saxena A, Sharma RK.
Nutritional aspect of nephrolithiasis.
Indian J Urol. 2010 Oct;26(4):523-30.

Singh PP, Barjatiya MK, Dhing S, Bhatnagar R, Kothari S, Dhar V.
Evidence suggesting that high intake of fluoride provokes nephrolithiasis in tribal populations.
Urol Res. 2001 Aug;29(4):238-44.

Yendt ER, Cohanim M.
Response to a physiologic dose of pyridoxine in type I primary hyperoxaluria.
N Engl J Med. 1985 Apr 11;312(15):953-7.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Good News About Coffee

cup-of-coffee-on-saucerThe inveterate coffee drinkers among us will appreciate the good news about one of our favorite beverages. After all the flak we took about the vices of coffee, now’s the chance to respond. After water and tea, coffee is the next most popular drink on the planet, having a starring role in the history of several cultures. It came from the Muslim world, travelled to Italy and then to the rest of Europe, finally landing in the New World. At one time, it was limited only to religious observances.

The coffee bean is contained inside a “cherry” that grows on a small evergreen bush.  The Arabica strain is the more highly regarded of the two chief varieties, but the robusta strain is more resistant to the diseases peculiar to this plant, though less flavorful and more bitter. Arabica prefers the coolness of the mountainside; robusta will grow at lower elevations and in warmer climates. Since the best tasting coffee really is mountain grown, the sales talk of a particular brand is true. But Mrs. Olsen never told us that other brands also use mountain grown beans. She merely capitalized on a little-known fact.

One effect of coffee consumption is moderately elevated blood pressure, which is not surprising because caffeine is a stimulant. Italian studies done in the early 1990’s found that 200 milligrams of caffeine, about two cups’ worth, could raise systolic blood pressure by 10% and diastolic by 5% for up to two hours after consumption. The mechanism points to vasoconstriction (which has its own benefits), but researchers found no variation in heart rate or cardiac contractility (Casiglia, 1991), leading to an assumption that this temporary state is not a major concern, especially in light of later studies that reported no association between long-term coffee consumption and increase of cardiovascular complications (Mesas, 2011) or risk of hypertension (Geleijnse, 2008) (Klag, 2002).

Vitamin B6, known as pyridoxine, is a nutrient occasionally used to tame morning sickness in pregnancy and the throes of PMS. It’s also been used to address homocysteine imbalance, carpal tunnel syndrome, immunity deficiencies, and various behavioral/psychiatric issues. However, careless dosing of vitamin B6 can cause medical concerns that outweigh the benefits of producing the monoamine neurotransmitters, serotonin and dopamine. Large doses of B6 over a period of time can cause nerve fiber damage, particularly auditory neuropathy. You’d never think that coffee can prevent and treat this malady, but it does (Hong, 2008). One active coffee component is called trigonelline (Hong, 2009), an alkaloid also found in pumpkin that is able to modulate blood glucose (van Dijk, 2009) (Yoshinari, 2009). Because auditory neuropathy may be attenuated by trigonelline, why can’t the peripheral neuropathy of diabetes or physical trauma likewise be eased? It’s worth a look (Zhou, 2012).

Late-life dementia and Alzheimer’s disease (AD) are concerns shared by an aging population across the globe. Finnish studies followed a number of middle-agers for more than twenty years, documenting their coffee (and tea) consumption along the way.  Focusing more on caffeine than on coffee’s lesser-known constituents, researchers found that, over the long haul, those who drank three to five cups of coffee a day at midlife had a lower risk of dementia and AD in old age (Eskelinen, 2009, 2010).  American studies later found that long-term coffee consumption protects against cognitive impairment by reducing the formation of amyloid beta, the protein that forms the plaques associated with AD. Here it was inferred that caffeine is part of a synergy that affords the desired effect, with many coffee constituents not yet identified (Cao, 2011).

Because early research had indicated that coffee may be protective against conditions other than neurological, scientists took the trigonelline link a little further. It’s accepted that people with diabetes are at risk for cognitive dysfunction. Initially, it was proposed that coffee was merely to be explored as a tool in the management of diabetes and related sequelae (Biessels, 2010). It was realized, however, that caffeine can decrease the risk of type 2 diabetes and consequent cognitive decline (Salazar-Martinez, 2004) (Tuomilehto, 2004).

In general, coffee increases plasma antioxidant capacity, possibly because of the contribution, bioavailability and activity of its particular group of polyphenols, including chlorogenic acid, one component linked to a reduction of type 2 diabetes risk by virtue of delaying intestinal glucose absorption and the inhibition of gluconeogenesis (Ong, 2010) (Tunnicliffe, 2011). Other medical conditions are purported to be influenced by coffee’s mechanisms, including gastrointestinal diseases (Inoue, 1998), gallstones (Leitzmann, 1999), and Parkinson’s disease (Checkoway, 2002) (Blanchette, 2000).

If coffee has a down side, it’s that it can interact with some drugs, most notably quinolone antibiotics, such as ciprofloxacin and its kin, which increase caffeine concentrations by inhibiting its clearance (Harder, 1989). Coffee’s popularity cannot be ignored. Just look at all the coffee options that run the gamut from hot to cold, from sweet to sweeter, and from low-cal to mega-cal. Since the 1989 expiration of a global agreement to stabilize supply, availability has fluctuated—and so has the price. You can’t even get the cup for a dime any more.

References

Biessels GJ.
Caffeine, diabetes, cognition, and dementia.
J Alzheimers Dis. 2010;20 Suppl 1:S143-50.

Campdelacreu J.
Parkinson disease and Alzheimer disease: environmental risk factors.
[Article in English, Spanish]

Neurologia. 2012 Jun 13. [Epub ahead of print]

Cao C, Wang L, Lin X, Mamcarz M, Zhang C, Bai G, Nong J, Sussman S, Arendash G.
Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer’s mice.
J Alzheimers Dis. 2011;25(2):323-35.

Casiglia E, Bongiovì S, Paleari CD, Petucco S, Boni M, Colangeli G, Penzo M, Pessina AC.
Haemodynamic effects of coffee and caffeine in normal volunteers: a placebo-controlled clinical study.
J Intern Med. 1991 Jun;229(6):501-4.

Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD.
Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake.
Am J Epidemiol. 2002 Apr 15;155(8):732-8.

Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M.
Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study.
J Alzheimers Dis. 2009;16(1):85-91.

Eskelinen MH, Kivipelto M.
Caffeine as a protective factor in dementia and Alzheimer’s disease.
J Alzheimers Dis. 2010;20 Suppl 1:S167-74.

Floegel A, Pischon T, Bergmann MM, Teucher B, Kaaks R, Boeing H
Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study.
Am J Clin Nutr. 2012 Apr;95(4):901-8.

Yoichi Fukushima, Takashi Ohie, Yasuhiko Yonekawa, Kohei Yonemoto, Hiroki Aizawa, Yoko Mori, Makoto Watanabe, Masato Takeuchi, Maiko Hasegawa, Chie Taguchi and Kazuo Kondo
Coffee and Green Tea As a Large Source of Antioxidant Polyphenols in the Japanese Population
Journal of Agricultural and Food Chemistry 2009 57 (4), 1253-1259

Gelber RP, Petrovitch H, Masaki KH, Ross GW, White LR.
Coffee intake in midlife and risk of dementia and its neuropathologic correlates.
J Alzheimers Dis. 2011;23(4):607-15.

Geleijnse JM.
Habitual coffee consumption and blood pressure: an epidemiological perspective.
Vasc Health Risk Manag. 2008;4(5):963-70.

Harder S, Fuhr U, Staib AH, Wolff T.
Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations.
Am J Med. 1989 Nov 30;87(5A):89S-91S.

Head KA.
Peripheral neuropathy: pathogenic mechanisms and alternative therapies.
Altern Med Rev. 2006 Dec;11(4):294-329.

Hermansen K, Krogholm KS, Bech BH, Dragsted LO, Hyldstrup L, Jørgensen K, Larsen ML, Tjønneland AM.
Coffee can protect against disease
Ugeskr Laeger. 2012 Sep 24;174(39):2293-2297.

Hong BN, Yi TH, Park R, Kim SY, Kang TH.
Coffee improves auditory neuropathy in diabetic mice.
Neurosci Lett. 2008 Aug 29;441(3):302-6. Epub 2008 Jun 22.

Hong BN, Yi TH, Kim SY, Kang TH.
High-dosage pyridoxine-induced auditory neuropathy and protection with coffee in mice.
Biol Pharm Bull. 2009 Apr;32(4):597-603.

Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, Grobbee DE, Batty D, Woodward M.
Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis.
Arch Intern Med. 2009 Dec 14;169(22):2053-63.

Inoue M, Tajima K, Hirose K, Hamajima N, Takezaki T, Kuroishi T, Tominaga S.
Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan.
Cancer Causes Control. 1998 Mar;9(2):209-16.

Kaiser permanante Division of Research
Coffee Drinking and Caffeine Associated with Reduced Risk of Hospitalization for Heart Rhythm Disturbances
3/2/2010

Klag MJ, Wang NY, Meoni LA, Brancati FL, Cooper LA, Liang KY, Young JH, Ford DE.
Coffee intake and risk of hypertension: the Johns Hopkins precursors study.
Arch Intern Med. 2002 Mar 25;162(6):657-62.

Leitzmann MF, Willett WC, Rimm EB, Stampfer MJ, Spiegelman D, Colditz GA, Giovannucci E.
A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.
JAMA. 1999 Jun 9;281(22):2106-12.

Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E.
The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis.
Am J Clin Nutr. 2011 Oct;94(4):1113-26. Epub 2011 Aug 31.

Oba S, Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, Shimizu H.
Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women.
Br J Nutr. 2010 Feb;103(3):453-9. Epub 2009 Oct 12.

Ong KW, Hsu A, Tan BK.
Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes.
PLoS One. 2012;7(3):e32718. Epub 2012 Mar 7.

Richelle M, Tavazzi I, Offord E.
Comparison of the antioxidant activity of commonly consumed polyphenolic beverages (coffee, cocoa, and tea) prepared per cup serving.
J Agric Food Chem. 2001 Jul;49(7):3438-42.

Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR.
Association of coffee and caffeine intake with the risk of Parkinson disease.
JAMA. 2000 May 24-31;283(20):2674-9.

Salazar-Martinez E, Willett WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, Hu FB.
Coffee consumption and risk for type 2 diabetes mellitus.
Ann Intern Med. 2004 Jan 6;140(1):1-8.

Tunnicliffe JM, Eller LK, Reimer RA, Hittel DS, Shearer J.
Chlorogenic acid differentially affects postprandial glucose and glucose-dependent insulinotropic polypeptide response in rats.
Appl Physiol Nutr Metab. 2011 Oct;36(5):650-9. Epub 2011 Oct 6.

Tuomilehto J, Hu G, Bidel S, Lindström J, Jousilahti P.
Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women.
JAMA. 2004 Mar 10;291(10):1213-9.

van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM.
Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance.
Diabetes Care. 2009 Jun;32(6):1023-5. Epub 2009 Mar 26.

Yoshinari O, Sato H, Igarashi K.
Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats.
Biosci Biotechnol Biochem. 2009 May;73(5):1033-41. Epub 2009 May 7.

Zhou J, Chan L, Zhou S.
Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease.
Curr Med Chem. 2012 Jul 1;19(21):3523-31.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.