Nutrition Journal - Latest Comments

New Email address

Keith Grimaldi — 2010-02-08T00:00:00Z

Please note that my new email addresses are:
keith.grimaldi@gmail.com
kgrimaldi@biomed.ntua.gr

Lithium is no nutrient, and orotate may not be so much better

Ben C — 2008-10-22T00:00:00Z

Lithium is not a part of the Dietary Reference Intakes, and so its classification as a nutrient in this paper is puzzling. I'm assuming that the authors do not consider it a nutrient, but an explicit qualification on that would have been nice. Similarly, St. John's Wort doesn't seem to be a nutrient.

The bigger problem is that lithium orotate may be not be so much more helpful, and Lakhan and Veira present an unfortunately one-sided view of the literature. I haven't looked at the papers they cite because I can't afford it, but other studies don't show conclusive evidence that lithium orotate crosses the blood-brain barrier more easily. Kling et al in 1978[1] found it increased uptake to the brain in rats when injected, but in 1976 Smith concluded that it didn't increase uptake to the brain.[2] In 1979 Smith et al tested again, and this time he found different results. He found that lithium orotate increased serum lithium concentrations higher, but was also deposited in the heart and kidney. He did not comment on the brain concentrations in his abstract, possibly because he did not want to admit that Kling was right (I only read the abstract).[3]

Lithium orotate probably deserves more attention and comparison with lithium carbonate than it gets. Smith seems inclined to look for the negative, and his 1976 finding was suspiciously anomalous. Nevertheless, it seems that lithium orotate does not only go to the brain. Even if it does go to the brain, it makes one wonder why the negative symptoms of lithium carbonate do not apply to lithium orotate. It seems as if these symptoms would be largely dependent upon the brain concentrations of lithium.

Thank you for the interesting paper, but please try to present a neutral view of the facts in the future. In many cases a more focused approach is better. I am hopeful for the future of nutrients in treating mental illness. Note that there are critical reviews of many of the substances discussed here. For example, in January 2008 the Current opinion in psychiatry concluded that the "evidence base for the efficacy of the majority of complementary and alternative interventions used to treat anxiety and depression remains poor".[4] In April 2008 a Cochrane review could only include 5 studies on omega-3 fatty acids and bipolar disorder, and of those only 1 provided data for analysis.[5]

Possibly these reviews are actively looking for the negative, and perhaps ignoring legitimate literature. In that case they need to be engaged, not ignored. To be fair, both of these aforementioned reviews were published around or after your review was published. I noticed that one of your peer reviewers mentioned these concerns, but somehow that reviewer dropped out of the picture.

Regards,

Ben Creasy

Is the instrument available?

Benjamin Littenberg — 2007-02-18T00:00:00Z

I found this article interesting and a potentially valuable contribution to the field of Health Literacy. However, I was disappointed that the instrument was not included in the article. It is very difficult to understand the strengths and weaknesses of a survey instrument that you can't look at. Is the instrument available?

Thank you for your good work!

Benjamin Littenberg, MD, Henry and Carleen Tufo Professor of Medicine & Professor of Nursing

Director, General Internal Medicine, University of Vermont

Obvious or erroneous?

Steve Hickey — 2007-02-12T00:00:00Z

Michael Donaldson’s paper includes erroneous and misleading points on vitamin C. The first is his assertion that oral intakes of vitamin C, even in multiple divided doses, are not as effective as intravenous (IV) administration for the treatment of cancer. There is insufficient data to support this statement.

Donaldson references Padayatty et al (2004), who provide limited evidence, based on plasma levels. These data do not show oral doses to be less therapeutically effective than IV. Donaldson has extrapolated from the results of in vitro experiments, over periods of hours, to oral treatments, lasting months. [1] A principle benefit of non-toxic redox therapies, based on vitamin C, is that patients can take them continuously for months, or even years. [2] To put it simply, just because a given level of vitamin C kills cancer cells quickly in a test tube, does not mean that a sustained, lower level will not be effective inside the human body.

Donaldson states that the amounts required for therapeutic effects are “obviously” beyond dietary intakes. This is not an obvious conclusion; it is an unjustified extrapolation, based on limited data. When measured over a period of hours, 200-250 microM/L vitamin C can be selectively cytotoxic to some cancer cells. This level can be built up using repeated (say, three hourly) oral dosing, to achieve a pharmacological steady state. Even if Donaldson’s conclusions were ultimately shown to be true for oral ascorbic acid, it is possible that liposomal formulations, given orally, could reach cytotoxic concentrations in plasma.

Furthermore, Donaldson’s assertion does not take into account possible combinations of vitamin C with other anti-cancer agents. For example, a synergistic combination of vitamin C with vitamin K3, or r-alpha-lipoic acid, is known to be many times more effective as an in vitro anticancer agent than vitamin C alone. Such a combination, taken orally, could reach therapeutic levels. Similarly, vitamin C, at an orally-achievable level of only 50-100 microM/L, drives motexafin gadolinium (a quinone drug, similar to vitamin K3) producing cytotoxicity and complete inhibition of proliferation over a 24 hour period. [3]

Another problem with Donaldson’s assertion relates to treatment resistance. The use of IV ascorbate typically provides a high plasma concentration, but in a series of pulses. Although this may shrink a tumour more quickly than is possible with oral doses (this has yet to be demonstrated), IV administration could ultimately be less effective at prolonging lifespan than oral dosing, which allows sustained plasma levels. [1] With standard chemotherapy, treatment becomes less effective with repeated courses of treatment, as cancer cells are selected for resistance. The same could happen with IV vitamin C.

Consider antibiotic therapy: the problems of resistant bacteria are minimised by providing a continuous selection pressure until the bacteria are gone. In practice, this means making sure the patient takes the full course. Intermittent pulses of antibiotic treatment would rapidly select for resistant organisms. Similarly, intermittent use of chemotherapy, or IV vitamin C, could favour treatment-resistant cancer cells. Until we have adequate experimental data, it is reasonable to combine intravenous vitamin C with maximal dynamic flow level oral dosing. This prevents the more resistant cancer cells having a treatment break, during which to regenerate.

Extrapolation from test tube studies to the living body ignores physiological actions. For example, tumours can absorb ascorbate, especially when glucose is restricted, concentrating it to levels above those of the plasma. By focusing on plasma levels, Donaldson runs the risk of underestimating the anti-tumour effects of vitamin C. [4] There are numerous anecdotal and clinical reports of the effectiveness of oral ascorbate in cancer.[5] However, current trials typically use inappropriate doses, both in magnitude and methodology.[6]

Assuming our choice was limited either to IV doses of ascorbate or oral doses (in association with a synergistic, redox-active agent, such as alpha-lipoic acid), it is certainly not “obvious” that intravenous ascorbate would be a more effective treatment for cancer patients. Indeed, one could make a strong argument that a suitable oral regime might offer a longer lifespan, with less chance of the disease recurring. In reality, we could choose to supplement dynamic flow level oral doses with intravenous ascorbate, thus gaining the advantages of each.

Current evidence suggests that ascorbate given alone is a relatively weak anticancer agent, but also that it is highly synergistic with other redox active nutrients. Appropriate research on the anticancer effects of vitamin C and related nutrients has been hindered by prejudice, for too long. It is time for a dispassionate examination of the science.

1. Hickey S Roberts H. (2005) Cancer: Nutrition and Survival, Lulu press.

2. Hickey S. Roberts H. Cathcart R (2005) Dynamic flow, a new model for ascorbate, Journal of Orthomolecular medicine, 20(4), 237-244.

3. Evens A.M. Lecane P. Magda D. Prachand S. Singhal S. Nelson J. Miller R.A. Gartenhaus R.B. Gordon L.I. (2005) Motexafin gadolinium generates reactive oxygen species and induces apoptosis in sensitive and highly resistant multiple myeloma cells, Blood, 105(3), 1265-1273. Epub 2004 Sep 23.

[4]. Hickey S. Roberts H. (2007) Selfish Cells, JOM, in press.

[5]. Gonzalez M.J. Miranda-Massari J.R. Mora E.M. Guzman A. Riordan N.H. Riordan H.D. Casciari J.J. Jackson J.A. Roman-Franco A. (2005) Orthomolecular oncology review: ascorbic acid and cancer 25 years later, Integr Cancer Ther, 4(1), 32-44.

6. Hickey S, Roberts H (2005) Misleading Information on the Properties of Vitamin C. PLoS Med 2(9): e307

Parents, not TV screens, should be targetted: A response to Dehghan, Akhtar-Danesh and Merchant

Owen Carter — 2006-03-26T00:00:00Z

Dehghan, Akhtar-Danesh and Merchant (2005) suggest that “numerous studies have shown that sedentary behaviors like watching television and playing computer games are associated with increased prevalence of obesity”. This statement is misleading, although it is true that data from North America, Europe and Oceania consistently indicate that childhood obesity and television viewing are related. Children watching above-average levels of television are approximately twice as likely to be obese (e.g., Wake, Hesketh & Waters, 2003; Janssen et al., 2005), however the correlational and cross-sectional nature of all such studies fails to suggest the direction of causation, so it might be equally true to say that obese children are twice as likely than their more svelte peers to undertake sedentary behaviours, such as watching television—which is equally plausible! Moreover, a meta-analysis of 52 studies by Marshall et al. (2004) suggested that time spent television viewing is able to explain only 0.5% of children’s body weight. Dehghan et al. also implicate playing video games but the same meta-analysis suggested there is virtually no relationship between time spent playing computer games and body weight at all. Interestingly the common presumption within the scientific literature is that children are more sedentary than previous generations due to increased television viewing behaviours (e.g., Eagle et al., 2004; Biddle et al., 2004; Bar-on, 2000). However, researchers have demonstrated that while access to television has increased in the past half a century, the amount of time that children spend watching television per capita has remained virtually unchanged throughout the intervening period, and furthermore time spent screen-viewing has merely displaced time formerly spent on other sedentary behaviours, such as going to the cinema, listening to music, reading comic books, playing board games, etc. (Carter, 2005; Marshall et al., 2004; Kaiser Family Foundation, 2004). As such interventions aimed at reducing childhood obesity by tackling television viewing and playing computer games are unlikely to have much affect at all. As highlighted by Dehghan et al., children’s energy consumption in developed countries has increased markedly in the past several decades—perhaps by around 15% in the last couple of decades. This alone is sufficient to explain increases in childhood obesity and explanations surrounding ‘decreases’ in physical activity levels are therefore superfluous. We merely need to recognise that increases in energy consumption have not been matched by increases in energy expenditure (i.e., physical activity).

Research suggests that a child with obese parents is ten-times more likely to be obese (Reilly et al., 2005). This raises the obvious scenario of an obese child’s environment where there is likely to be ready access to large quantities of energy-dense foods, provided by his or her parents, who also consume such. Given that obesity in adulthood is far higher than in childhood, perhaps the best way to tackle childhood obesity is to first tackle adult obesity. This need not be insurmountable: it has been estimated that for most of the population, a reduction of only 420KJ per day would be sufficient to stop weight gain in 90% of the population (Murray et al., 2005; Hill et al., 2003). This is the equivalent of walking an additional 2,000 steps, or drinking one cup less of soft drink or cordial. This should therefore be the concrete and easily understood message we promote to both children and adults, and especially parents, if we want to get serious about reducing the burgeoning epidemic of childhood obesity.

REFERENCES

Bar-on ME. (2000) The effects of television on child health: implications and recommendations. Arch Dis Child, 83(4):289-92.

Biddle S, Gorely T, Marshall S, I M, N C. Physical activity and sedentary behaviours in youth: issues and controversies. Journal of the Royal Society for the Promotion of Health, 124(1):29-33.

Eagle L, Bulmer S, de Bruin A, Kitchen PJ. (2004) Exploring the link between obesity and advertising in New Zealand. J Market Comm, 10:49-67.

Hill JO, Wyatt HR, Reed GW, Peters JC. (2003) Obesity and the environment: where do we go from here? Science 299(5608):853-5.

Kaiser Family Foundation (2004) The Role of Media in Childhood Obesity. Washington: The Henry J. Kaiser Family Foundation, 2004:12.

Marshall S, Biddle SJH, Gorely T, Cameron N, Murdey I. Relationships between media use, body fatness and physical activity in children and youth: a meta-analysis. International Journal of Obesity 2004;28(10):1238-1246.

Murray R, Frankowski B, Taras H. (2005) Are soft drinks a scapegoat for childhood obesity? J Pediatr 146(5):586-90.

Janssen I, Katzmarzyk PT, Boyce WF, Vereecken C, Mulvihill C, Roberts C, et al. (2005) Comparison of overweight and obesity prevalence in school-aged youth from 34 countries and their relationships with physical activity and dietary patterns. Obes Rev, 6(2):123–32.

Reilly JJ, Armstrong J, Dorosty AR, Emmett PM, Ness A, Rogers I, et al. (2005) Early life risk factors for obesity in childhood: cohort study. BMJ, 330(7504):1357.

Wake M, Hesketh K, & Waters E. (2003) Television, computer use and body mass index in Australian primary school children. J Paediatr Child Health, 39(2):130–4.

Consider pediatric use of the Waist-to-Height ratio

Henry Kahn — 2005-10-04T00:00:00Z

Your brief review of alternative definitions for pediatric obesity might also have considered the Waist-to-Height ratio (WHtR). This relatively simple index has been shown in at least 3 publications (citations below) to perform better than BMI or BMI percentiles for identification of children at risk of cardiometabolic disorders. Interestingly, this ratio may not require standardization for either sex or age of the children. Thus, its application in pediatric clinics could reduce the confusion that currently surrounds the interpretation of pediatric BMIs.

There are no publications that suggest what might be the cutpoints for defining an adverse WHtR value. The definition(s) of such cutpoints would depend, of course, on the their intended purpose. They might also vary depending on the population under examination.

References:

Savva SC, Tornaritis M, Savva ME et al. Waist circumference and waist-to-height ratio are better predictors of cardiovascular disease risk factors in children than body mass index. Int J Obes Relat Metab Disord. 2000;24(11):1453-1458.

Hara M, Saitou E, Iwata F, Okada T, Harada K. Waist-to-height ratio is the best predictor of cardiovascular disease risk factors in Japanese schoolchildren. J Atheroscler Thromb. 2002;9(3):127-132.

Kahn HS, Imperatore G, Cheng YJ. A population-based comparison of BMI percentiles and waist-to-height ratio for identifying cardiovascular risk in youth. J Pediatr. 2005;146(4):482-488.

An Alternative Reason Why Medium-Quantity Lutein might have Similar Effectiveness against AMD to that of Zeaxanthin

John Rokos — 2004-10-20T00:00:00Z

We know that both the foveal and perifoveal regions take up zeaxanthin, whereas uptake of lutein by the more visually active foveal region is negligible. However, anecdotally it was not the zeaxanthin sources like egg yolk, maize, orange peppers and persimmon that were quoted as being associated with protection against loss of vision due to AMD, but the highly lutein-rich green leafy vegetables like spinach, collard greens and kale. It may be for this reason that retinal conversion of lutein to zeaxanthin is suggested in the literature. I should like to propose a rationale for the possible effectiveness of lutein that does not postulate chemical conversion:

Because of its size, the total binding capacity of the perifoveal region for zeaxanthin might exceed that of the foveal region, with the result that much of the zeaxanthin that gets into the region of the macula could end up in the perifoveal region, thereby failing to benefit the foveal region. When increased amounts of lutein are ingested, perifoveal receptors, that would otherwise bind zeaxanthin, might be occupied by the ingested lutein. Assuming the same overall total level of zeaxanthin in the region, a result would be an increase in the zeaxanthin available to the foveal receptors, thus improving the level of protection to the foveal region.

In this model, lutein additional to that required for saturating the perifoveal receptors would achieve no useful purpose and, indeed, might deletoriously compete with zeaxanthin for transport to the region. Supplements that contain large quantities of lutein without significant quantities of zeaxanthin should perhaps, therefore, be taken at a different time from that of a zeaxanthin-containing meal or snack, or not taken at all (this is additional to the other warnings about supplements in the article).

"A calorie is a calorie": does it truly contradict thermodynamics?

Giuseppe Marineo — 2004-10-06T00:00:00Z

Dear Sirs,

In regard to the article “A calorie is a calorie violates the second law of thermodynamics” by Feinman RD et al (Nutr J 2004; Jul 28;3:9 ), I believe it is a useful brief thought on the proper application and interpretation of thermodynamics in nutrition.

We agree with several aspects of the article and with its overall meaning. However, we believe there are still some potential conflicts regarding the analytical methods to be used when a complex system such as the biological one is considered. This occurs because we are forced to use a number of general laws and conceptually adjust them to biology with its complexity and dynamics.

To examine energy transformations from a thermodynamic point of view, we adopt the definition from physics of a calorie as the thermic energy needed to increase the temperature from 14.5°C to 15.5°C of 1g of distilled water at 1 atm pressure, even though the concepts are not wholly applicable to biology. In such a context, the concept of a calorie used by nutritionists implies a somewhat arbitrary and "static" equivalence which isn't suitable to thermodynamics. Briefly, since the thermic energy cannot be directly utilized, the free energy of glucose (or other nutrients) does not have a clear functional definition since it is practically impossible to foresee whether and how such substrates will be transformed in work and heat, nor the efficiency of their conversion which is understandably variable in a complex and dynamic system such as the biological one (mainly due to the ever increasing entropy of the total system).

As an example, I believe that we might agree that the thermogenesis of an individual exposed to low temperature (below the physiological one) has to be regarded as useful work. Thus, heat production corresponds to an effective utilization of available energy by contributing to homeostasis. However, the same thermogenesis occurring in an individual exposed to a temperature higher than normal, forces the body to use the available energy to produce work and recruits other physiological responses such as sweating etc.). Since vital chemical reactions cannot be shut down. I believe that even in considering apparently simple phenomena such as thermogenesis / thermoregulation, we cannot ignore the complexity and properties of what is a dynamic system. Such properties may change over a very short time, changing the related thermodynamics.

Since the complexity of biological systems is a primary factor and not secondary to thermodynamic processes, we believe it isn’t possible to use a specific conceptual analysis to clarify the relationship between calorie and body weight, beyond “conceptually-guided” probability calculations [1, 2].

G. Marineo, F. Marotta

Delta Research & Development, Bioengineer Research Center, affiliated to “Tor Vergata” University, Rome.

Via di Mezzocammino 85

00127, Rome, Italy

g.marineo@mclink.it

References:

1. Marineo G, Marotta F, Sisti G (2004). Cirrhosis progression as a model of accelerated senescence: affecting the biological aging clock by a breakthrough biophysical methodology. Ann. NY Acad. Sci. 1019: 572-576.

2. Marineo, G. Marotta, F.. Biophysics of aging and therapeutic interventions by entropy-variation systems. BioGerontology 2004 (in press)