Wednesday, July 10, 2013

This Nutrient Improves Night Driving

Eyes function differently based on the level of light in the environment. In normal daylight the eye primarily uses cones to focus the light. In near darkness, the eye primarily uses rods to focus the light. Low light conditions such as driving at night require both mechanisms. Lutein is an orange-red carotenoid pigment produced by plants and is present in the diet in colorful fruits and vegetables. One of the best sources of lutein is kale which provides more than 20 mg per cup. Cooked spinach, collard greens and turnip greens also pack a similar punch. This compares to romaine lettuce and raw spinach which have less than 4 mg of lutein available for use.

In the body, lutein is one of the predominant pigments concentrated in the macula, a specialized area of the eye that is responsible for central vision. In addition, it is known to be deposited in the skin. It is thought that lutein’s functional role in these vulnerable tissues is to protect against sunlight-induced free radical production.
Ever since the Blue Mountain Eye Study reported that higher dietary lutein and zeaxanthin intake reduced the risk for incident of age-related macular degeneration (AMD) over 5 and 10 years, significant interest has been placed on these particular carotenoids.[1]

In an interesting study, middle-aged adults who drove for a living (i.e. taxi drivers) were given 20 mg of lutein or a placebo for one year. Researchers measured a variety of outcomes including something called macular pigment optical density (MPOD) [2] MPOD has been associated with improvements in visual function in those with age-related macular degeneration.[3]

This study showed that supplemental lutein, at this dose, increases serum levels of lutein.  However, of key importance is the length of the study and the measurement of vision performance. Under low light conditions, the group receiving treatment of lutein performed better at testing of contrast sensitivity and glare sensitivity. MPOD was also increased.

No significant side effects were reported in this study. Carotenodermia is one concern of large doses of carotenoids and while transient and relatively harmless, it was not seen in this study.  Previous studies have considered doses of 6 and 12 mg and showed peak serum lutein levels after 3-6 months.[4], [5], [6], [7] However, in this research, peak levels were seen after just 30 days. This was attributed to the higher dose and good compliance among participants. While following serum levels of a specific carotenoid often does not typically have clinical value, uptake of lutein by the macula can take several months following peak levels. Indeed, this effect was seen in this study as well. Despite seeing a six-fold increase in serum levels after only one month, visual performance did not improve until three months after initiation of lutein administration. While 6 mg did not improve macular pigment optical density (MPOD) in previous studies, this study confirmed increases in this valuable biomarker.4 Several hypotheses remain about how macular pigment plays a role in the health of the eye but a leading theory is that antioxidants in the pigment reduce oxidized products produced by the interaction of light and tissues.

One of the challenges of the study was that serum levels of lutein in the participants at baseline were found to be lower than expected. It is thought that profession or economic status could play a role in this. Unfortunately, it creates another question. If a person already has adequate lutein levels in serum, will they not benefit from supplementation? This remains to be determined.

Another question that may arise concerns other carotenoids. The family of carotenoids (including beta carotene, alpha carotene, astaxanthin, zeaxanthin and others) may compete for absorption and excess dosing of a single carotenoid may hypothetically lead to insufficiencies among the other phytonutrients. Unfortunately, serum levels of these other carotenoids were not measured at baseline or throughout the study.

Essentially, participants taking lutein in this study could not read a Snellen chart, the tool with the large E at the top that optometrists and physicians use, any better than the placebo group after a year of use. Visual acuity was not significantly different. However, seeing movement in the periphery under low light conditions was improved. This is interesting because visual performance is more of a real-life analysis. Especially in this demographic studied, those whose job requires long hours of driving, even minor improvements in vision can result in improved driving performance and safer roads. Up to 23% of car accidents have been associated with reduced visual performance.[8] The challenge of the results of this study is the age-group that was studied. Young to midlife adults are not often the ones commonly complaining of decreased night vision. More often than not, the aging person no longer trusts their ability to navigate in low light conditions and this may result in decreased activity and a lower perceived quality of life. As people age, reduced participation in activity is a concern for incidence of depression. Those who continue to drive despite declining vision are putting themselves and others at risk. It would be curious to see if similar results could be replicated in an older population. Until that result is published, people may find this relatively inexpensive and safe intervention worth a one year trial for themselves.



[1] Tan JS,Wang JJ, Flood V, Rochtchina E, SmithW, Mitchell P. Dietary antioxidants and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology 2008;115(2):33441.
[2] Lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study. Nutrition (2013), http://dx.doi.org/10.1016/j.nut.2012.10.017
[3] Weigert G, Kaya S, Pemp B, Sacu S, Lasta M, Werkmeister RM, Dragostinoff N, Simader C, Garhöfer G, Schmidt-Erfurth U, Schmetterer L.Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011 Oct 17;52(11):8174-8. doi: 10.1167/iovs.11-7522.
[4] Sasamoto Y, Gomi F, Sawa M, Tsujikawa M, Nishida K. Effect of 1-year lutein supplementation on macular pigment optical density and visual function. Graefes Arch Clin Exp Ophthalmol 2011;249:184754.
[5] Ma L, Lin XM, Zou ZY, Xu XR, Li Y, Xu RA. 12-week lutein supplementation improves visual function in Chinese people with long-term computer display light exposure. Br J Nutr 2009;102:18690.
[6] Nolan JM, Loughman J, Akkali MC, Stack J, Scanlon G, Davison P, et al. The impact of macular pigment augmentation on visual performance in normal subjects: COMPASS. Vision Res 2011;51:45969.
[7] Olmedilla B, Granado F, Blanco I, Vaquero M. Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind, placebo- controlled pilot study. Nutrition 2003;19:214.
[8] Ranny T. Psychological factors that influence car-following and car following model development. Transportation Res 1999;Part F 2:2139.

Melatonin and Type II Diabetes

In a study observing 370 women (nurses) who developed diabetes between 2000 and 2012 and 370 women (also nurses) who did not develop diabetes during this time frame the major urinary metabolite of melatonin (6-sulfatoxymelatonin) was measured against urinary creatinine. This was a part of the Nurses' Health Study cohort.[1]

This study provides a correlation between the lowest level of melatonin metabolite secretion and the development of type 2 diabetes. Women with the highest excretion of 6-sulfatoxymelatonin developed diabetes at a rate of 4.27 cases per 1000 while women with the lowest excretion of 6-sulfatoxymelatonin developed diabetes at a rate of 9.27 cases per 1000. This provides 2.17 times the risk for development of type 2 diabetes for those with low excretion.

Upon the initial publication of these results, two immediate camps developed. One camp, excited to explore the therapeutic uses of supplemental melatonin and then another that dismissed the data due to the nature of the study. It is correct to indicate that this information alone does not allow for mass medication of those with type 2 diabetes or for use in prophylaxis. However, researchers did an excellent job of addressing confounding issues within the scope of known physiologic mechanisms.

With diabetes on the rise, and 1 in 10 American adults wielding the diagnosis, this information is welcomed if it is interpreted correctly and cautiously.

The first question that must be addressed is if urinary excretion of 6-sulfatoxymelatonin is an adequate surrogate for nocturnal melatonin secretion from the pineal gland. Secretion of melatonin follows a daily pattern peaking 3-5 hours after sleep onset when it is dark with almost no production during daylight. Fortunately, the urinary excretion of 6-sulfatoxymelatonin when normalized to urinary creatinine has been used to estimate overnight melatonin secretion. This is good news since nocturnal plasma evaluation is impractical in the outpatient setting.[2],[3] Of interest is that this same biomarker was used to provide evidence for a statistically significant inverse association between melatonin levels, as measured in overnight morning urine, and invasive breast cancer risk in postmenopausal women.[4]

The next question may be in regards to the relationship between disrupted sleep and type 2 diabetes.[5] Researchers noted sleep disruption by two factors: snoring and sleep duration. Both of these factors were self-reported which may lead to limitation of information.

Another question arises in regards to the mechanism of how melatonin, a hormone typically associated with sleep directly affect glucose metabolism. Researchers suggest it may have to do with insulin secretion but human studies are lacking in this area. Most research is done on rodents and this is potentially problematic. Rodents are primarily nocturnal creatures and have different circadian patterns. While rats and mice may derive specific health benefits from exogenous administration of melatonin, it doesn’t always mean that humans will derive the same benefit to the same magnitude. However, the work that has been done so far piques curiosity. Oral consumption of melatonin protected rats prone to diabetes from developing increased cardiovascular and diabetes risk markers while being fed a high-calorie diet.[6] Melatonin administration to insulin-resistant mice reversed insulin resistance and improved glucose metabolism.[7] Human in-vitro studies have pointed to a kinase pathway that supports pancreatic islet cells.[8],[9],[10]

While some may discount summarily the study because it is done with nurses, all women, mostly (97%) Caucasian, and prone to shift work, that may be a premature dismissal. Interestingly, the nurses involved in this nested group of the Nurses’ Health Study reflected very little shift work perhaps due to age and seniority. It is true though that results can only be attributed to women and a limited racial heritage.
So while it is too early to suggest the use of melatonin as adjunctive care to glucose metabolism, it will likely be several years before type, dose, and timing of administration will be available in the peer-reviewed literature. One thought in integrative medicine is to normalize levels similar as how vitamin D is often recommended rather than a set dose. However, no agreed upon reference range has been established for urinary 6-sulfatoxymelatonin: creatinine although the highest quartile in this study had a median ratio of 67.0 ng/mg. Because melatonin is a hormone from outside of the body, the recommendation of lowest effective dose may apply similarly to the recommendation of hormone therapy.[11]

While melatonin may not be ready for the lime-light in diabetes, low-dose melatonin is something to keep in mind when caring for those patients at risk or suffering from the condition.

Natural Health International is the proud manufacturer and distributor of Herbatonin the first plant-based melatonin available in 3 mg and 0.3 mg



[1] McMullan CJ, Schernhammer ES, Rimm EB, Hu FB, Forman JP. Melatonin secretion and the incidence of type 2 diabetes. JAMA. 2013 Apr 3;309(13):1388-96. doi: 10.1001/jama.2013.2710.
[2] Lang U, Kornemark M, Aubert ML, Paunier L, Sizonenko PC. Radioimmunological determination of
urinary melatonin in humans: correlation with plasma levels and typical 24-hour rhythmicity. J Clin Endocrinol Metab. 1981;53(3):645-650.
[3] Baskett JJ, Cockrem JF, Antunovich TA. Sulphatoxymelatonin excretion in older people: relationship
to plasma melatonin and renal function. J Pineal Res. 1998;24(1):58-61.
[4] Schernhammer ES, Berrino F, Krogh V, Secreto G, Micheli A, Venturelli E, Sieri S, Sempos CT, Cavalleri A, Schünemann HJ, Strano S, Muti P. Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women.J Natl Cancer Inst. 2008 Jun 18;100(12):898-905. doi: 10.1093/jnci/djn171. Epub 2008 Jun 10.
[5] Wagner, Kelly. "Sleep Laboratory Finds Insomnia With Short Sleep Duration Is A Risk Factor For Diabetes." Medical News Today. MediLexicon, Intl., 11 Jun. 2009. Web.
13 May. 2013. <http://www.medicalnewstoday.com/releases/153361.php>
[6] Prunet-Marcassus B, Desbazeille M, Bros A, et al. Melatonin reduces body weight gain in Sprague Dawley rats with diet-induced obesity. Endocrinology. 2003; 144(12):5347-5352.
[7] Cuesta S, Kireev R, Garcı´a C, Rancan L, Vara E, Tresguerres JA. Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-
accelerated prone male mice (SAMP8). Age (Dordr). 2012.
[8] Kemp DM, Ubeda M, Habener JF. Identification and functional characterization of melatonin Mel 1a
receptors in pancreatic beta cells: potential role in incretin-mediated cell function by sensitization of cAMP signaling. Mol Cell Endocrinol. 2002;191(2):157-166.
[9] Ramracheya RD, Muller DS, Squires PE, et al. Function and expression of melatonin receptors on human pancreatic islets. J Pineal Res. 2008;44(3): 273-279.
[10] Picinato MC, Hirata AE, Cipolla-Neto J, et al. Activation of insulin and IGF-1 signaling pathways
by melatonin through MT1 receptor in isolated rat pancreatic islets. J Pineal Res. 2008;44(1):88-94.
[11] http://www.fda.gov/forconsumers/byaudience/forwomen/ucm118624.htm

Caffeine Withdrawal Now a Mental Disorder

While many of us thought that paying $5 for a tasty herbal beverage was the real mental disorder, we’ll have to wait for the next psychiatric manual for that diagnosis because a new one is on the table.

If you are a committed coffee drinker or enjoy a few too many caffeinated sodas or drinks on the weekends and are considering modifying your habits, your morning routine and entire world as you know it now has new implications. You may be crazy.

The DSM-V (American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders version five) has a quirky new diagnosis that may affect you. It is called withdrawal from caffeine intoxication. The diagnosis is well meaning. People who consume 250 mg of caffeine can experience caffeine intoxication and can fundamentally change their brain chemistry and the withdrawal period of this drug, yes drug, is now a listed and recognized diagnostic mental disorder. How much is 250 mg?
·      12 ounces (Tall) Starbucks Coffee            
·      32-56 ounces of green tea, brewed for 3 minutes            
·      100 ounces of most sodas (5 – 20 ounce bottles)
·      1.5-16 ounce cans of most energy drinks
·      1.9 ounces of 5-Hour Energy (contains about 208 mg)

Caffeine-related disorders include intoxication which first made it into the DSM-IV in 2011 with symptoms of restlessness, nervousness, excitement, insomnia, flushed face, excessive urination (diuresis), gastrointestinal disturbance, muscle twitching, rambling flow of thought and speech, tachycardia or cardiac arrhythmia, periods of inexhaustibility or unintentional motion (psychomotor agitation).

Caffeine withdrawal and its inclusion as a mental disorder started rumbling almost 10 years ago when an article appeared in Psychopharmacology where researchers from American University (Washington, DC a bastion of caffeine consumption) wrote about the symptoms of withdrawal including
·       Headache
·       Fatigue
·       Decreased energy/activeness
·       Decreased alertness
·       Drowsiness
·       Decreased contentedness
·       Depressed mood
·       Difficulty concentrating
·       Irritability
·       Foggy/not clearheaded
·       Flu-like symptoms
·       Nausea/vomiting
·       Muscle pain/stiffness

With a list of symptoms like this, I’m starting to believe this should be included in the manual. They go on to say “the incidence of headache was 50% and the incidence of clinically significant distress or functional impairment was 13%.” Those are high numbers for withdrawal from a widely available, freely distributed, and highly utilized drug.  

During the first few days of withdrawal, those who drop caffeine cold turkey display all of the tell-tale signs of an addict. They often search for every version of “coffee-methadone” they can find. Yes, the symptoms are transient, but they are intense. Headache and irritability top the symptom list.

What is interesting to me is that they noted that these symptoms of caffeine withdrawal tend to occur 12-24 hours after the high and continue for 2-9 days.

And this may come as no shock, but the higher the daily dose of caffeine, the worse the symptoms. What I found really curious is that symptoms were caused by doses as low as 100 mg. They concluded, mind you, this is 2004, “The caffeine-withdrawal syndrome has been well characterized and there is sufficient empirical evidence to warrant inclusion of caffeine withdrawal as a disorder in the DSM and revision of diagnostic criteria in the ICD.” It is 2013 and now it is included. So instead of being shocked, maybe we should be appalled at how long this inclusion took!

There is a take home point. For those who are embarking upon a new detoxification program, a new health habit, or simply shifting your gears in relation to the food, supplements, or medications you are using, please remember that it is not always the addition of a substance that causes symptoms, but it can also be the removal of substances that causes symptoms (or improvements). So, don’t just tell your healthcare practitioner what you started to fix your problem, but also tell them what you stopped. 

Reference: Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl). 2004 Oct;176(1):1-29. Epub 2004 Sep 21.