Nutrition Journal - Latest Comments

Low cholesterol is associated with highest mortality; worse in women?

eddie vos — 2012-07-05T04:27:03Z

The authors[1] express ¿deep concern¿ about cholesterol levels in northern Swedes increasing since 2007 as well as about the ¿long-term deleterious effects of a high cholesterol level...¿

Such concerns are not based on mortality data and where in fact low cholesterol levels are associated with early death in most of the world¿s data sets and of which 2 studies are particularly relevant to central and northern Europeans. The first is from adjacent northern Norway[2] while the second one is a long-term follow-up study in Austria that in participants equals the one of the authors[3].

The study in Norway found the highest mortality in men and women in the lowest quartile for Total Cholesterol (TC) with, in women, the mortality risk (adjusted for age, smoking, and systolic blood pressure) dropping linearly to the top quartile (TC = less than 5 mM/L -vs- TC = greater than 7 mM/L; Figure 2 in[2]). The trend in men is not as clear with the lowest mortality happening in the second quartile of TC = 5 to 5.9 mM/L.

The Austrian study also found the highest mortality in the lowest quartile for TC and that only in women under the age of 50 was not statistically significant. On the other hand, in women over the age of 50, the risk of early death of being in the bottom quartile for TC equaled the risk of smoking (about +60%; p = less than 0.001; Table 4B in[3]).

The concept that lower cholesterol levels are healthy has to be re-examined since being in the low cholesterol quartiles may predict ill health[3] and early death[2,3].

The authors cite the famed 4S cholesterol-lowering Scandinavian trial[42in1] but that ended with 3 more female heart patient deaths on simvastatin than there were on placebo; in fact, there are no cholesterol-lowering studies ever done even suggesting a mortality benefit in women (references in [4]). In other words, the statin trials have conclusively proven that lowering cholesterol in women does not reduce mortality -- and the we know that "naturally" having low cholesterol is a mortality risk in older Europeans.

It would therefore be useful if the authors could comment on the foregoing and on cholesterol and on all-cause mortality in their own data set.

1. Johansson I, Nilsson L, Stegmayr B, Boman K, Hallmans G, Winkvist A. Associations among 25-year trends in diet, cholesterol and BMI from 140,000 observations in men and women in Northern Sweden. Nutr J. 2012 Jun 11;11(1):40. Medline 22686621

2. Petursson H, Sigurdsson JA, Bengtsson C, Nilsen TI, Getz L. Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study. J Eval Clin Pract. 2012 May 29. Medline 22639974.

3. Ulmer H, Kelleher C, Diem G, Concin H. Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality. J Womens Health (Larchmt). 2004 Jan-Feb;13(1):41-53. Medline 15006277

4. Vos E, Rose C. Questioning the benefits of statins. Can Med Ass'n J. Nov. 8, 2005. 173(10) 1207 DOI:10.1503/cmaj.1050120 www.cmaj.ca/cgi/reprint/173/10/1210.pdf

Another aspect of the difference between high intake of folate and vitamin B12 on lipid profile

Ahmad Saedisomeolia — 2012-01-06T14:39:31Z

Title of commentary:
Another aspect of the difference between high folate and vitamin B12 intake on lipid profile

Commentary letter about article:
¿Plasma folate levels are associated with the lipoprotein profile a retrospective database analysis: Semmler et al: Nutrition Journal. 2010; 9: 31¿

Commentary by: Roya Kolahdouz Mohammadi (MSc in Nutrition Sciences), Assistant Professor Ahmad Saedisomeolia (PhD in Nutrition Sciences)

Department of Nutrition and Biochemistry, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Comment:
In this paper, it has been shown that: high folate levels are associated with increased levels of HDL, lower levels of LDL and a lower LDL/HDL ratio. However, vitamin B12 is not associated with the lipoprotein profile. The explanation of the authors about the possible reasons for the positive relationship between folate levels and favorable lipid profile is supposed to be incomplete. This commentary letter encourages the readers of this paper to think about one of the most possible explanations of this relationship.
However, folate and vitamin B12 serve as single-carbon transporters (and play a key role in inhibition of homocystein production which is supported by the authors of the article), there is a fundamental difference between folate and vitamin B12. Folate is provided mostly from plant foods, however, the most significant natural dietary source of vitamin B12 is animal foods. Therefore, we believe that high folate level is resulted from a healthy diet (including: high plant food, high dietary fiber intake, less saturated fat and low calorie diet) [1]. On the other hand, high vitamin B12 levels are expected to be related to high animal food sources [reviewed in [2] which may affect inversely on favorable lipid profile. Therefore, it is suggested to the readers of this paper to consider the other aspect of the difference between high folate and vitamin B12 group studied in this paper. We conclude that the difference between the nutritional patterns of the participants (whether they are consuming plant or animal foods) can affect their lipid profile.

References:
1. De Biase, S.G., et al., Vegetarian diet and cholesterol and triglycerides levels. Arq Bras Cardiol, 2007. 88(1): p. 35-9.
2. Watanabe, F., Vitamin B12 sources and bioavailability. Exp Biol Med (Maywood), 2007. 232(10): p. 1266-74.

In reference to comment entitled 'Questions'

Andrea Melendez-Acosta — 2011-07-26T11:13:46Z

The article to which this comment refers was not press released by Nutrition Journal nor BioMed Central (the journal publisher). The journal or the publisher has no connection with the website or author of the piece mentioned in the website above.

Questions

Douglas Kalman — 2011-07-25T17:00:22Z

Thank you for posting and publishing this study.

A few questions:

1. Why utilize a IRB from Mexico when the study was apparently conducted in the United States? It appears that the study was conducted at a site in Orange County and there are plenty of California-based IRB's available for study and study conduct review and approval (i.e., Aspire IRB). Please explain.

2. Why allow such puffery as in this press release (http://www.nutraingredients-usa.com/Research/Futureceuticals-builds-science-defends-IP-for-coffee-fruit-extract/) since the product that appeared to be studied had over 10 ingredients and not just one that is promoted in this press release, this appears to water down the science and weaken the overall study.

Interview structure as additional file?

Marjukka Mäkelä — 2011-06-07T11:04:30Z

Thank you for your paper which we are using at the Nordic Course of Evidence-Based Health Care as an example of a well-done qualitative study. Our group would have liked to see the questions you used (the interview schedule) as supplementary material.

New Email address

Keith Grimaldi — 2010-02-08T12:04:33Z

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 — 2008-10-22T10:18:25Z

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 — 2007-02-18T23:13:12Z

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 — 2007-02-12T00:07:00Z

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 — 2006-03-26T04:22:52Z

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.